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FUNCTIONAL ANATOMY OF THE CEREBROSPINAL FLUID PATHWAYS The ventricular system: The ventricles of the brain include the paired lateral ventricles, 3 rd and 4th ventricles. Lateral ventricles (ventriculus lateralis): The two lateral ventricles are irregular cavities situated in the lower and medial parts of the cerebral hemispheres, one on either side of the midline. They are separated from each other by a median vertical partition, the septum pellucidum, but communicate with the 3rd ventricle and indirectly with each other through the interventricular foramena of Monro. They are lined by a thin membrane; the ependyma covered by ciliated epithelium and contain cerebrospinal fluid. Each lateral ventricle is a Cshaped cavity which extends from its anterior horn in the frontal lobe in a continuous curve posteriorly (central part), then inferiorly, and finally anteriorly, to end in the temporal lobe as the inferior horn. From its convex posterior surface a posterior horn extends backwards to a variable extent into the occipital lobe. The size and shape of this ventricle is very variable. In the young, the walls lie almost in opposition, while with increasing age and loss of neural tissue the ventricle expands and may reach a considerable size without an increase in its internal pressure (Gray et al., 1995). The anterior horn or cornu of the lateral ventricle curves inferiorly into the frontal lobe from the interventricular foramen. It is triangular in coronal section .The narrow floor is formed by the rostrum of the corpus callosum; the roof and anterior wall by the trunk and genu of the corpus callosum; the vertical medial wall by the septum pellucidum and column of the fornix; the lateral wall by the bulging head of the caudate nucleus (Drake et al., 2010). The central part of the ventricle: Also called body of the lateral ventricle, it is roofed by the trunk of the corpus callosum. Its medial wall, which decreases in height as it is followed posteriorly, is formed by the fornix and septum pellucidum anteriorly, and by the fornix posteriorly. The floor consists from lateral to medial of the following structures: The caudate nucleus. The thalamostriate vein runs anteriorly in the groove between thalamus and caudate nucleus. The stria terminalis runs with the thalamostriate. A narrow strip of the dorsal surface of the thalamus. The choroid plexus. The fornix: anteriorly it is a rounded bundle but posteriorly it becomes progressively flattened and extends laterally into the floor of the lateral ventricle. The posterior horn or cornu begins at the splenium of the corpus callosum, and extends posteriorly into the occipital lobe, tapering to a point. The roof, lateral wall, and floor are formed by a sheet of fibers (tapetum) from the splenium of the corpus callosum. The medial wall is invaginated by two ridges; the upper of these (bulb of the posterior horn) is formed by the fibers of the forceps major ( Skinner et al., 2009). The inferior horn is the direct continuation of the ventricular cavity into the temporal lobe. It runs inferiorly, posterior to the thalamus, and then passes anteriorly, curving medially to end at the uncus. The lateral wall is formed by the tapetum of the corpus callosum. The roof, which can be seen on the inferior surface of the 'frontal' part of the brain, consists of the white matter which passes laterally into the temporal lobe. The floor is broad posteriorly where the inferior and posterior horns meet, and is often raised (collateral triangle) by the collateral sulcus. Anteriorly its floor narrows and its medial part is formed by a convex ridge produced by the hippocampus covered by a layer of nerve fibers (the aveus) which passes medially from the hippocampus to form a ridge on its medial border (fimbria of the hippocampus). The amygdaloid body is an oval mass of grey matter which overlies the tip of the inferior horn of the ventricle in the uncus (Drake JM, 1998). Fig. (4): Ventricles of the brain (BradburyM.W.B,1985) Fig. (5): Cast of the ventricles of the brain, left lateral aspect. In this brain, the right posterior horn is considerably longer than the left. The key drawing indicates related solid structures in parentheses .(Ros Lopez 2009). The trigone of the lateral ventricle is that portion where the three major components (body, inferior horn, and occipital horn) merge to form a common cavity. It is indented by the bulb of the posterior horn superiorly, the collateral eminence inferiorly, the calcaravis medially. Anteriorly in the trigone, the glomus of the choroid plexus lies on the thalamus along with the posterior portion of the fornix (Skinner et al., 2009). The third ventricle: This narrow slit like cavity lies in the median plane between the two halves of the diencephalons. It extends from the lamina teriminalis anteriorly, to the superior end of the aqueduct and root of the pineal posteriorly. The roof of the ventricle consists of a layer of ependyma which is invaginated on each side by the overlying vascular pia mater to form a minute, linear choroids plexus. The roof is attached on both sides to the striamedullaris thalami. The floor extends posteriorly from the optic recess on the superior surface of the optic chiasma into the infundibular recess, and then passes, above the mamillary bodies and the tegmentum of the midbrain, to the aqueduct.(Viale et al ; 2001). The anterior commissure indents the anterior wall of the ventricle at the superior end of the lamina terminalis. Immediately posterior to this the column of the fornix forms a low ridge in the lateral wall. Posterior to the column of the fornix, and almost hidden by it, is a small, obliquely placed aperture which opens into the lateral ventricle. This is one half of the interventricular foramen, and it forms the only communication between the lateral ventricles and the other cavities of the brain. On each side, the narrow strip of choroid plexus in the roof of the third ventricle becomes continuous with the choroid plexus of the corresponding lateral ventricle through the interventricular foramen, and this is often so narrow that it is nearly filled by the choroid plexus. Thus any hypertrophy of the plexus at this situation easily blocks the communication between the two ventricles, causing an increase in pressure in the lateral ventricle. If this is unilateral, it may be sufficient to cause compression of the opposite hemisphere and a shift of the midline structures towards that side (Drake R.L,2010). The cerebral aqueduct (aqueductus cerebri; aqueduct of Sylvius) Is a narrow canal, about 15 mm. long, situated between the corpora quadrigemina and tegmenta, and connecting the third with the fourth ventricle. Its shape, as seen in transverse section, varies at different levels, being T-shaped, triangular above, and oval in the middle; the central part is slightly dilated, and was named in the past, the ventricle of the mid-brain. It is lined by ciliated columnar epithelium, and is surrounded by a layer of gray substance named the central gray stratum: this is continuous below with the gray substance in the rhomboid fossa, and above with that of the third ventricle (Gray et al, 1995). Fig. (6): Median sections. Shows important features of the brain stem and a cross section of the midbrain. The interthalamic adhesion is indicated by an asterisk. B emphasizes the meninges, subarachnoid space, and cisterns. Aq., aqueduct; Ep., epiphysis (pineal body); 1, fissure prima; 2, fissure secunda; 3 and 4, third and fourth ventricles. The interrupted line indicates the orbitomeatal plane, which has been used for orientation, thereby rendering the brain stem almost vertical (Swenson M.R., 2007). The Fourth Ventricle: (ventriculus quartus): This is the diamond shaped cavity of the hindbrain which extends from the superior border of the pons to the middle of the medulla oblongata. It lies behind these structures and in front of the cerebellum and the medullary vela. It narrows above to the superior angle where it becomes continuous with the cerebral aqueduct in the midbrain. The tiny central canal of the inferior half of the medulla oblongata and spinal medulla opens into it at the inferior angle (Skinner et al, 2009). The ventricle is widest at the junction of the pons with the medulla oblongata .Here it extends laterally on each side, to form a tubular lateral recess, which curves over the posterior aspect of the inferior cerebellar peduncle .This recess passes as far as the tip of the flocculus, where it opens into the subarachnoid space through the lateral aperture (foramen of Lushka) of the fourth ventricle, posterior to the ninth and tenth cranial nerves. The deepest part of the ventricle is opposite the inferior part of the pons. Immediately inferior to this, the inferior medullary velum passes anteriorly and the ventricle becomes a shallow slit, the median part of the thin roof of the fourth ventricle curves posteriorly on the anterior surface of the uvula of the cerebellum to the margin of the median aperture (foramen of Magendie) of the fourth ventricle (Badie, 2007). By means of the lateral and median apertures the ventricle communicates with the subarachnoid cavity, and the cerebrospinal fluid can circulate from one to the other (Massimi L,2013). Roof or dorsal wall superior to the cerebellar recess, the superior or anterior medullary velum with the lingula of the cerebellum fused to its posterior surface (Drake J.M, 1998 ). Fig. (7): The ventricular system of the human brain (Badie, 2007) Choroid plexus of the lateral ventricles: Projecting into the lateral ventricle at its medial side is a highly vascularized fringe of pia mater and ependyma, namely the choroid plexus of the lateral ventricle, part of a larger structure, the telachoroidae. Its pial basis is invaginated during development along a linear region of the medial hemispheric wall the choroid fissure- where no nervous tissue develops ;hence the pia directly contacts the ventricular ependyma, the two tissues being fused to form the choroid plexus, which otherwise consists chiefly of small blood vessels ,capillaries and nerve fibers. It extends anteriorly to the interventricular foramen, where it is continuous across the third ventricle with the plexus of the opposite ventricle (Gray et al, 1995). In the central part of each lateral ventricle, the plexus lies at the lateral extremity of a sheet of pia mater- telachoroidae of the third and lateral ventricles which covers the dorsal surface of the thalamus and the roof of the 3rd ventricle (Viale et al;2001). Choroid plexus of the third ventricle: The roof of the 3rd ventricle is covered by and adherent to a reduplicated fold of the pia mater, the telachoroidae, from the surface of which a pair of parasagittal vascular fringes, choroid plexuses, project vertically downwards, invagination the ependymal roof into the cavity) (badie, B ,2007). The blood supply of choroid plexuses in the telachoroidae is from the anterior choroidal branch of the internal carotid and choroidal branches of the posterior cerebral artery, the former usually a single vessel, the latter three to five in number. The two sets anastomose to some extent Capillaries drain into a rich venous plexus, served by a single choroidal vein leaving the telachoroidae, commencing near each basal (posterolateral) angle of the tela. These veins drain directly into the internal cerebral vein or indirectly by way of the thalamostriate vein near the foramen of Monro. These veins also drain into the basal vein of Rosenthal directly or by way of the inferior ventricular vein (Skinner et al, 2009). Choroid plexus of the 4th ventricle: These consist of two highly vascular inflexions of the telachoroidae, which invaginate the lower part of the roof of the ventricle and are everywhere covered by the epithelial lining of the cavity. Each consists of a vertical and a horizontal portion: the former lies close to the middle line, and the latter passes into the lateral recess and projects beyond its apex (Skinner et al, 2009). Fig. (8): The picture above shows the location of the choroid plexus in 3d-notice that it is largely found superior to both the lateral ventricles. The lateral ventricles are illustrated in pink, the third and the fourth ventricle is shown in green. The choroid plexus is illustrated in red (Patel A.D, 2003). The subarachnoid cisterns: The arachnoid and pia mater develop from a single mass of loose connective tissue immediately surrounding the central nervous system, inside the dura mater. Cerebrospinal fluid from the cavities of the brain percolates into this tissue, separating it into an outer layer, the arachnoid, applied to the internal surface of the dura mater, and an inner layer, the pia mater, applied to the surface of the central nervous system, with the subarachnoid space between them. Linings of the cavities: The cerebrospinal fluid is separated from direct contact with its adjacent tissues by membranes made up of single layers of cells, with or without adjacent connective tissue; these membranes are: the ependyma, pia mater and arachnoid. Communication between the Ventricular System and Subarachnoid Pathways: Communication between the ventricular system and the subarachnoid system in man is by way of three foramina. A median opening in the roof of the fourth ventricle, the foramen of Magendie, establishes a communication with the large cerebellum-medullary cistern. The lateral recesses of the fourth ventricle wind around the medulla, passing over the base of the inferior cerebellar peduncles. These recesses open into the subarachnoid space on the basal aspect of the brain as the foramina of Luschka. Each foramen is situated in the angle between the pons and medulla, and opens into the cisterna pontis on the basal aspect of the brain stem (Davson, 1967) The drainage mechanism of CSF arachnoid granulations and villi: Arachnoid granulations are wart-like projections into the dural sinuses and are actually outgrowths of the arachnoid into the dural and the endothelial lining of the sinuses. Arachnoid villi are also invasions of the dura by arachnoid but on a microscopic scale. Fig. (9): The meninges. Above panel is a midsagittal view showing the three layers of the meninges in relation to the skull and brain. Below panels are blowups to show details of arachnoid graduation in relation to the venous sinus (Badie, B, 2007). Cerebrospinal Fluid Valves: The villus could be best described as a labyrinth of coated tubules, from 4 to 12 microns in diameter, connecting with each of them and opening into the subarachnoid space, on one hand, and the venous channels of the dura on the other. These tubes may be visualized as one-way valves that open only in one direction so as to prevent back flow of-blood into the CSF. The Blood-Brain Barrier and the Cerebrospinal Fluid: There are two major types of fluid in the CNS; an interstitial fluid ISF which accounts for 15-18% of the volume of the CNS and bathes parenchyma keeping its internal milieu constant, and the cerebrospinal fluid CSF. Fig. (10): The course of the cerebrospinal fluid (CSF). Arrows lead from the choroid plexuses of the lateral and third ventricles toward the aqueduct. The fluid thereby formed is joined by that produced in the fourth ventricle and passes through the median aperture to the cerebello-medullary cistern of the subarachnoid space. The fluid then extends (1) upward around the brain and (2) downward around the spinal cord. The inset (a coronal section at the sagittal suture) shows the drainage of the C.S.F. into the venous system (superior sagittal sinus, S, and lateral lacunae, L, by way of arachnoid granulations, G). Various adjacent vessels are also included. A, cerebral artery; C, cerebral vein; 0, diploic vein; E, emissary vein; M, meningeal vein; 3 and 4, third and fourth ventricles. The lowermost part of the figure shows the caudal end of the spinal cord. lumbar puncture (L.P.) is performed in the part of the subarachnoid space that lies below the termination of the spinal cord ( Skinner et al, 2009) The blood-CSF barrier: Secretion of the choroids plexuses is within 500 ml CSF per day and this fluid circulated as mentioned earlier. The subarachnoid space is sealed off by the arachnoid mater Whose cells are bonded by tight junctions. The net flow through these membranes is normally outward: ventricular and brain CSF diffuses into ISF and brain ISF diffuses into the subarachnoid space. The blood CSF barrier resides in specialized ependymal epithelium overlying the choroidal capillaries (davson, 1967). Fig. (11): The blood-brain and blood-CSF barriers showing the daily formation of 500 ml of CSF(swanson, M.R, 2007). 17 Anatomy of the Anterior Abdominal Wall The abdomen represents the portion of the trunk between the thorax and pelvis. The abdominal structure will be described from the most superficial layer to the peritoneum. SUPERFICIAL FASCIA. The abdominal wall consists of skin, superficial fascia, fat, muscles, transversalis fascia, and the parietal peritoneum. The panniculus adiposus consists of the fat deposits in the superficial fascial layer often referred to as Camper’s Fascia. Scarpa’s fascia is the membranous deeper layer to this, which contains more fibrous tissue. The fibrous layer is formed by compacted fibrous strata that are in continuity with the fatty layer. ANTERIOR MUSCULATURE . Much of the strength of the abdominal wall is inherent in four paired muscles and their respective aponeuroses. These aponeuroses represent sheet-like tendons for the insertion of the lateral muscles and also form the sheath of the rectus abdominis. From most superficial to deep, the external oblique is the first layer of the lateral muscles (Fig12 ). The largest of the three, the external oblique arises from the lower 8 ribs posteriorly to interdigitate with both the serratus and latissimus muscles. The direction of the fibers is approximately horizontal in the uppermost portion only to become oblique in the lowest portions as they fold on them- selves to form the inguinal ligament. After contributing to the anterior portion of the rectus abdominis sheath, the remaining fibers insert onto the linea alba, which is the dense white line formed by the medial termination of all the aponeuroses. (Gray et al, 1995). 18 The internal oblique arises from the anterior two-thirds of the iliac crest and lateral half of the inguinal ligament to run essentially at right angles to those of the external oblique. The fibers take the shape of the iliac crest in that they fan out to insert on the 10th to 12th ribs inferiorly. Fig.(12) musculature of anterior abdominal wall ( external oblique – internal oblique – tansversus abdominis – rectus abdominis ) (Gray et al, 1995). The umbilicus marks an important level in the division of the internal oblique aponeurosis. Above this level, the aponeurosis of the internal oblique splits to envelop the rectus abdominis and subsequently rejoins at the linea alba. The transversus abdominis muscles arise from the 7th to 12th costal cartilages, iliac crest, and the lateral third of the inguinal ligament. The muscle bundles of this group run essentially horizontally, except the lower most medial fibers, which run a more inferomedial course to their insertion on the pubic crest and pectin pubis. 19 The umbilicus is an important landmark in the division of the transversus abdominis muscle fibers. Above the umbilicus the transversus abdominis aponeurosis joins the internal oblique aponeurosis to form a portion of the posterior rectus sheath. Below the umbilicus, the transversus aponeurosis only contributes to the anterior rectus sheath. Fig.(13) The rectus sheath above and below arcuate line, (Bruni o semin ,2001). The arcuate line (of Douglas) is the site at which termination of these contributing fibers onto the posterior aspect of the rectus abdominis muscle occurs. The principal vertical muscle of the anterior abdominal wall consists of a pair of muscles separated by the linea alba. The rectus abdominis is therefore invested within a sheath derived from the combined aponeuroses and fasciae of the external oblique, internal oblique, and transversus abdominis wall consists of a pair of muscles separated by the linea alba. 20 The rectus abdominis muscle originates from the 5th through 7th costal cartilages to insert on the symphysis pubis and crest. Superiorly, the rectus is wide, broad, and thin, becoming narrow and thick inferiorly. The rectus muscle and sheath form the linea semilunaris laterally. Segmentation of each rectus muscle occurs by tendinous intersections that represent attachment of the rectus muscle with the anterior layer of the rectus sheath .(skinner et al,2009) Fig.(14) The rectus sheath at various levels.(skinner et al,2009), Peritoneal Cavity The abdominal viscera are contained either within a serous membrane–lined cavity called the abdominopelvic (sometimes just “abdominal” or “peritoneal”) cavity or lie in a retroperitoneal position adjacent to this cavity, often with only their anterior surface covered by peritoneum (e.g., the kidneys 21 and ureters). The abdominopelvic cavity extends from the abdominal diaphragm inferiorly to the floor of the pelvis. The walls of the abdominopelvic cavity are lined by parietal peritoneum, which can reflect off the abdominal walls in a double layer called a mesentery, which embraces and suspends a visceral structure. As the mesentery wraps around the viscera, it becomes visceral peritoneum. Viscera suspended by a mesentery are considered intraperitoneal, whereas viscera covered on only one side by peritoneum are considered retroperitoneal. Anatomists refer to the peritoneal cavity as a “potential space,” since it normally contains only a small amount of serous fluid that lubricates its surface. If excessive amounts of fluid collect in this space due to edema (ascites) or hemorrhage, then it becomes a “real space.” Many clinicians, however, view the cavity only as a real space because it does contain serous fluid but qualify this distinction further when ascites or hemorrhage occurs. The abdominopelvic cavity is further subdivided into the following Greater sac: most of the abdominopelvic cavity Lesser sac: also called the omental bursa; it is an irregular part of the peritoneal cavity that forms a cul-de-sac space posterior to the stomach and anterior to the retroperitoneal pancreas; it communicates with the greater sac via the epiploic foramen (of Winslow) Additionally, the peritoneal cavity contains a variety of double-layered folds of peritoneum in addition to the mesenteries that suspend the bowel. These include the omenta (attached to the stomach) and peritoneal ligaments; these are not ligaments in the traditional sense, but are short, distinct mesenteries that connect structures (for which they are named) together or to the abdominal wall. 22 1: Anatomy of the vertebral column: Structure of the vertebrae Vertebrae normally vary in size and other characteristics from one region of the vertebral column to another and to a lesser degree within each region; however, their basic structure is the same. A typical vertebra could be represented by the 2nd lumbar vertebra and consists of: Vertebral body, Vertebral arch, Seven processes. 1 (Fig 1). Vertebral body: The vertebral body consists of vascular, trabecular (spongy, cancellous) bone enclosed by a thin external layer of compact bone (Fig. 2). The trabecular bone is a meshwork of mostly tall vertical trabeculae intersecting with short, horizontal trabeculae. The interstices of these trabeculae are occupied by red marrow that is among the most actively hematopoietic (blood-forming) tissues of the mature individual. One or more large foramina in the posterior surface of the body accommodate basivertebral veins that drain the marrow (Fig. 1). The vertebral body is the most massive, roughly cylindrical, anterior part of the bone that gives strength to the vertebral column and supports body weight. The size of the vertebral bodies increases as the column descends, most markedly from T4 inferiorly, as each bears progressively greater body weight. 1 Most of the superior and inferior surfaces of the vertebral body are covered with discs of hyaline cartilage (vertebral end plates), which are remnants of the cartilaginous model from which the bone develops. 2 In dried laboratory and museum skeletal specimens, this cartilage is absent, and the exposed bone appears spongy, except at the periphery where an epiphyseal rim or ring of smooth bone, derived from an annular epiphysis, is fused to the body (Fig.23 1B). In addition to serving as growth zones, the annular epiphyses and their cartilaginous remnants provide some protection to the vertebral bodies and permit some diffusion of fluid between the IV disc and the capillaries in the vertebral body. The superior and inferior epiphyses usually unite with the centrum, the primary ossification center for the central mass of the vertebral body (Fig. 1B), early in adult life at approximately age 25. The vertebral notches are indentations observed in lateral views of the vertebrae superior and inferior to each pedicle between the superior and inferior articular processes posteriorly and the corresponding projections of the body anteriorly (Fig. 1 C & D). The superior and inferior vertebral notches of adjacent vertebrae and the IV discs connecting them form the intervertebral foramina (Fig. 1D), in which the spinal (posterior root) ganglia are located and through which the spinal nerves emerge from the vertebral column with their accompanying vessels.1 24 Figure 1: A typical vertebra, represented by L2. A. Functional components include the vertebral body (bone color), a vertebral arch (red), and seven processes: three for muscle attachment and leverage (blue) and four that participate in synovial joints with adjacent vertebrae (yellow). B and C. Bony formations of the vertebrae are demonstrated. The vertebral foramen is bounded by the vertebral arch and body. A small superior vertebral notch and a larger inferior vertebral notch flank the pedicle. D. The superior and inferior notches of adjacent vertebrae plus the IV disc that unites them form the IV foramen for the passage of a spinal nerve and its accompanying vessels. Note that each articular process has an articular facet where contact occurs with the articular facets of adjacent vertebrae (B and D). 1 25 Figure 2. Internal aspects of vertebral body and vertebral canal. Vertebral bodies consist largely of spongy bone, with tall, vertical supporting trabeculae linked by short horizontal trabeculae, covered by a relatively thin layer of compact bone. Hyaline cartilage end plates cover the superior and inferior surfaces of the bodies, surrounded by smooth bony epiphyseal rims. The posterior longitudinal ligament, covering the posterior aspect of the vertebral bodies and linking the IV discs, forms the anterior wall of the vertebral canal. Lateral and posterior walls of the vertebral canal are formed by vertebral arches (pedicles and laminae) alternating with IV foramina and ligamenta flava.1 Vertebral arch: The vertebral arch is posterior to the vertebral body and consists of two (right and left) pedicles and laminae (Fig. 1A). The pedicles are short and cylindrical processes that project posteriorly from the vertebral body to meet two broad, flat plates of bone, called laminae, which unite in the midline. The vertebral arch and the posterior surface of the vertebral body 26 form the walls of the vertebral foramen (Fig. 1 B & C). The succession of vertebral foramina in the articulated vertebral column forms the vertebral canal (spinal canal), which contains the spinal cord and the roots of the spinal nerves that emerge from it, along with the membranes (meninges), fat, and vessels that surround and serve them (Fig. 3 E)1. Figure 3. Vertebral column and vertebral canal, demonstrating its five regions. A. This anterior view shows the isolated vertebral column. B. This right lateral view shows the isolated vertebral column. The isolated vertebrae are typical of each of the three mobile regions. Note the increase in size of the vertebrae as the column descends. C. This posterior view of the vertebral column includes the vertebral ends of ribs, representing the skeleton of the back. D. This medial view of the axial skeleton in situ demonstrates its regional curvatures and its relationship to the cranium (skull), thoracic cage, and hip bone. The continuous, weight-bearing column of vertebral bodies and IV discs forms the anterior wall of the vertebral canal. The lateral and posterior walls of the canal are formed by the series of vertebral arches. The IV foramina (seen also in part B) are openings in the lateral wall through which spinal nerves exit the vertebral canal. The posterior wall is formed by overlapping laminae and spinous processes, like shingles on a roof. E. This sagittal MRI study shows the primary contents of the vertebral 27 canal. The medullary cone (L. conus medullaris) is the cone-shaped inferior end of the spinal cord, which typically ends at the L1-L2 level in adults. The dura mater, the external covering of the spinal cord (gray), is separated from the spinal cord by a fluid-filled space (black) and from the wall of the vertebral canal by fat (white) and thin-walled veins (not visible here). 1 Seven processes arise from the vertebral arch of a typical vertebra (Fig. 1A&C): One median spinous process projects posteriorly (and usually inferiorly, typically overlapping the vertebra below) from the vertebral arch at the junction of the laminae. Two transverse processes project posterolaterally from the junctions of the pedicles and laminae. Four articular processes (zygapophyses) two superior and two inferior also arise from the junctions of the pedicles and laminae, each bearing an articular surface (facet). The former three processes, one spinous and two transverse, afford attachments for deep back muscles and serve as levers, facilitating the muscles that fix or change the position of the vertebrae. The latter four (articular) processes are in apposition with corresponding processes of vertebrae adjacent (superior and inferior) to them, forming zygapophysial (facet) joints (Fig. 1 D). Through their participation in these joints, these processes determine the types of movements permitted and restricted between the adjacent vertebrae of each region. They also assist in keeping adjacent vertebrae aligned, particularly preventing one vertebra from slipping anteriorly on the vertebra below. Generally, the articular processes bear weight only temporarily, as when one rises from the flexed position, and unilaterally when the cervical vertebrae are laterally flexed to their limit. However, the inferior articular processes of the L5 vertebra bear weight even in the erect posture.1 Vertebral canal The spinal cord lies within a bony canal formed by adjacent vertebrae and soft tissue elements (the 28 vertebral canal) : the anterior wall is formed by the vertebral bodies of the vertebrae, intervertebral discs, and associated ligaments; the lateral walls and roof are formed by the vertebral arches and ligaments.3 Within the vertebral canal, the spinal cord is surrounded by a series of three connective tissue membranes called the meninges. The meninges The pia mater is the innermost membrane and is intimately associated with the surface of the spinal cord; The second membrane, the arachnoid mater, is separated from the pia by the subarachnoid space, which contains CSF; The thickest and most external of the membranes, the dura mater, lies directly against, but is not attached to, the arachnoid mater.3 Contents of the vertebral canal The spinal cord, spinal nerve roots, and spinal meninges and the neurovascular structures that supply them are located within the vertebral canal (Fig. 4).1 In the vertebral canal, the dura mater is separated from surrounding bone by an extradural (epidural) space containing loose connective tissue, fat, and a venous plexus.3 29 Figure 4: Innervation of periosteum and ligaments of vertebral column and of meninges. Except for the zygapophysial joints and external elements of the vertebral arch, the fibroskeletal structures of the vertebral column (and the meninges) are supplied by the (recurrent) meningeal nerves. Although usually omitted from diagrams and illustrations of spinal nerves, these fine nerves are the first branches to arise from all 31 pairs of spinal nerves and are the nerves that initially convey localized pain sensation from the back produced by acute herniation of an IV disc or from sprains, contusions, fractures, or tumors of the vertebral column itself. (Based on Frick H, Kummer B, Putz R: Wolf-Heidegger's Atlas of Human Anatomy, 4th ed. Basel, Karger AG, 1990:476.) 1 Spinal cord The spinal cord is the major reflex center and conduction pathway between the body and the brain. This cylindrical structure slightly flattened anteriorly and posteriorly, is protected by the vertebrae and their associated ligaments and muscles, the spinal meninges, and the CSF. The spinal cord begins as a continuation of the medulla oblongata (commonly 30 called the medulla), the caudal part of the brainstem. In adults, the spinal cord is 42-45 cm long and extends from the foramen magnum in the occipital bone to the level of the L1 or L2 vertebra. However, its tapering inferior end, the medullary cone, may terminate as high as T12 vertebra or as low as L3 vertebra. Thus the spinal cord occupies only the superior two thirds of the vertebral canal.1 The spinal cord is enlarged in two regions in relationship to innervation of the limbs. The cervical enlargement extends from the C4 through T1 segments of the spinal cord, and most of the anterior rami of the spinal nerves arising from it form the brachial plexus of nerves that innervates the upper limbs. The lumbosacral (lumbar) enlargement extends from T11 through L1 segments of the spinal cord, inferior to which the cord continues to diminish as the medullary cone. The anterior rami of the spinal nerves arising from this enlargement make up the lumbar and sacral plexuses of nerves that innervate the lower limbs.1 The external surface of the spinal cord is marked by a number of fissures and sulci: The anterior median fissure extends along the length of the anterior surface; the posterior median sulcus extends along the posterior surface; the posterolateral sulcus on each side of the posterior surface marks where the posterior rootlets of spinal nerves enter the cord.3 Spinal nerve roots Each spinal nerve is connected to the spinal cord by posterior and anterior roots: The posterior root contains the processes of sensory neurons carrying information to the CNS .The cell bodies of the sensory neurons, which are derived embryologically from neural crest cells, are clustered in a spinal ganglion at the distal end of the posterior root, usually in the intervertebral foramen. The anterior root contains motor nerve fibers, which carry signals away from the CNS. The cell bodies31of the primary motor neurons are in anterior regions of the spinal cord .Medially, the posterior and anterior roots divide into rootlets, which attach to the spinal cord. 3 In embryos, the spinal cord occupies the full length of the vertebral canal, thus spinal cord segments lie approximately at the vertebral level of the same number, the spinal nerves passing laterally to exit the corresponding IV foramen. By the end of the embryonic period (8th week), the tail-like caudal eminence has disappeared, and the number of coccygeal vertebrae is reduced from six to four segments. The spinal cord in the vertebral canal of the coccyx atrophies. During the fetal period, the vertebral column grows faster than the spinal cord; as a result, the cord ascends relative to the vertebral canal.1 At birth, the tip of the medullary cone is at the L4-L5 level. Thus, in postnatal life, the spinal cord is shorter than the vertebral column; consequently, there is a progressive obliquity of the spinal nerve roots (Fig 5). Because the distance between the origin of a nerve's roots from the spinal cord and the nerve's exit from the vertebral canal increases as the inferior end of the vertebral column is approached, the length of the nerve roots also increases progressively. 1 The lumbar and sacral nerve roots are therefore the longest, extending far beyond the termination of the adult cord at approximately the L2 level to reach the remaining lumbar, sacral, and coccygeal IV foramina. This loose bundle of spinal nerve roots arising from the lumbosacral enlargement and the medullary cone and coursing within the lumbar cistern of CSF caudal to the termination of the spinal cord resembles a horse's tail, hence its name ”the cauda equine” ( horse tail).1 Arising from the tip of the medullary cone, the terminal filum descends among the spinal nerve roots 32 in the cauda equina. The terminal filum (filum terminale) is the vestigial remnant of the caudal part of the spinal cord that was in the tail-like caudal eminence of the embryo. Its proximal end (the pial part or internal terminal filum) consists of vestiges of neural tissue, connective tissue, and neuroglial tissue covered by pia mater. The terminal filum perforates the inferior end of the dural sac, gaining a layer of dura and continuing through the sacral hiatus as the dural part or external terminal filum (also known as the coccygeal ligament) to attach to the dorsum of the coccyx. The terminal filum is an anchor for the inferior end of the spinal cord and the spinal meninges. 1 33 Figure 5. Vertebral column, spinal cord, spinal ganglia, and spinal nerves. Lateral and posterior views illustrating the relation of the spinal cord segments (the numbered segments) and spinal nerves to the adult vertebral column. 34 1 The Cerebrospinal Fluid (CSF) is produced by vascular plexuses in the Ventricles. All of the ventricles are filled with a clear, watery fluid, the cerebrospinal fluid (CSF). Most of the fluid is produced by vascular tufts the choroid plexus. This is present in all four ventricles, but the largest amount is found in the lateral ventricles. The choroid plexuses are attached to the wall of the ventricles with thin stalks (tela choroidea). The average volumes of CSF are (Damkier et al. 2013): 1. 50 mL in the newborn and increases with age. 2. 90 mL in children 4 to 13 years old. 3. 150 mL in adults. The rate of formation is approximately 0.35 ml/min or 500 ml/day. Approximately 14% of total volume turns over every hour. The rate at which CSF forms remains relatively constant and declines only slightly as CSF pressure increases. In contrast, the rate of absorption increases linearly as CSF pressure exceeds 7 mm Hg. At a pressure of 20 mm Hg, the rate of absorption is three times the rate of formation (Damkier et al. 2013). 35 The capacity for drainage is two to four times the normal rate of CSF production. The villi can behave as one-way valves, in that they are closed by high pressure in the venous sinus and opened by high CSF pressure (Barshes et al. 2005). CSF production Most of the CSF is produced within the ventricular system by the choroid plexus. However, a sizable proportion some 10% to 20%, evidently is formed by the parenchyma of cerebrum and spinal cord. The accepted view is that CSF bulk flow occurs from the site of its production in the ventricles to its absorption in the arachnoid granulations. In the adult human, production of CSF is independent of pressure however; a prolonged and marked increase in intraventricular pressure owing to hydrocephalus can slightly reduce the rate of CSF formation (Ross & Lamperti 2010). CSF appears to be formed in a two-step process: The 1st step is the formation by hydrostatic pressure of a plasma ultrafiltrate through the non-tight-junction choroidal capillary endothelium into the connective tissue stroma. The passage is driven by hydrostatic pressure. The 2nd step is ultra-filtrate transformation subsequently into a secretion by an active metabolic process within the choroidal epithelium. The astrocytic surface extrudes sodium into the ventricle, followed by osmotically drawn water (Damkier et al. 2013). 19 36 Anatomy & Physiology CSF absorption 80% enters directly into the cisternal system with subsequent drainage from the cerebral subarachnoid space into the cortical venous system, 20% circulates into the subarachnoid space of the spinal cord. Yet Spinal descent of CSF however, might prove to be an important alternative pathway in pathologic conditions. CSF drainage occurs in part by way of the arachnoidal villi and granulations. These are essentially microtubular invaginations of the subarachnoid space into the lumen of large dural and venous sinuses (Barshes et al. 2005). Three factors control CSF drainage: 1-CSF pressure: The normal CSF pressure at the reference level (the foramen of Monro) in the recumbent adult is 100-200mm H2O (7-15mmHg) with mean pressures of 20mmHg regarded as elevated. Pressures from 0-7mmHg do not usually signify any pathology. The CSF pressure fluctuates with the arterial pulse wave and respiratory excursions. 2-Pressure within the dural sinuses and the cortical venous system: CSF is absorbed into the venous system through the arachnoid villi associated with the major dural sinuses, predominantly the superior sagittal sinus. The present view proposes a hydrostatic pressure-dependent system between the CSF and venous sinus blood with an opening threshold (Schaller 2004). 3-Resistance of the arachnoid villi to CSF flow Changes in any of these variables significantly affect CSF flow. It appears that drainage does not depend on the colloid osmotic pressure 37 20 Anatomy & Physiology difference between CSF and sinus blood because the tubules are permeable to protein (Schaller 2004). CSF also can drain through the lymphatics as it was observed that children with an obstructed CSF-diverting shunt occasionally develop nasal congestion and periorbital or facial swelling. The lymphatic drainage of CSF might play a role in the pathophysiology of hydrocephalus, either as an alternative pathway for drainage or in cases of impaired access to the lymphatic system, as a cause of hydrocephalus. Also the periventricular hypodensity in the presence of hydrocephalus which is seen at CT and MRI scans is the result of CSF migrating into the area surrounding the ventricles in the presence of increased intraventricular pressure. CSF also can drain from the subarachnoid spaces surrounding the cranial and spinal nerve root sleeves, with entry into the lymphatic system (Sakka et al. 2011). CSF circulation in brain CSF passes from the paired lateral ventricles through foramina of Monro into the single midline third ventricle, and then flows down the single midline aqueduct of Sylvius into the single midline fourth ventricle. CSF leaves the ventricular system through the two lateral foramina of Luschka and the midline foramen of Magendie. Here CSF is shown exiting through the foramen of Magendie and entering the cisterna magna. Within the subarachnoid space CSF flows over the convexities of the brain and the folia of the cerebellum and around the brainstem. From the cisterna magna CSF also courses inferiorly to surround the spinal cord (Sakka et al. 2011). 38 21 Anatomy & Physiology The cerebrospinal fluid becomes blood plasma again and the rate of reabsorption normally equals the rate of production (Hamilton et al. 2012). Figure 9: CSF flow from choroid plexus to their absorption in the arachnoid villi. Quoted from (Damkier et al. 2013). CSF Functions Since cerebrospinal fluid is tissue fluid, one of its functions is to bring nutrients to CNS neurons and to remove waste products to the blood as the fluid is reabsorbed. The other function of cerebrospinal fluid is to act as a cushion for the central nervous system. The brain and spinal cord are enclosed in fluid-filled membranes that absorb shock. Naturally this protection has limits very sharp or heavy blows to the skull will indeed cause damage to the brain (Schaller 2004). 39 22 Anatomy & Physiology CSF flow dynamics The flow is a result of cardiac pulsations transmitted to intracranial arteries and capillaries, causing a specific series of CSF and brain parenchyma displacements. In normal conditions, CSF shows an alternating upward (diastolic) and downward (systolic) motion in each cardiac cycle that can be recognized and measured in the ventricular system, cisterns, and subarachnoid spaces. In healthy persons, antegrade flow of CSF is initiated at the foramen of Monro at 8% of the cardiac cycle. The wave of CSF flow continues through the aqueduct into the proximal fourth ventricle. At the time CSF is flowing in an antegrade direction through the aqueduct it is also flowing in an antegrade direction through the pontine cistern and upper cervical subarachnoid space. Onset of retrograde flow is initiated at 42% of the cardiac cycle, first in the posterior cervical subarachnoid space and lower fourth ventricle followed by retrograde flow starting in the aqueduct at 54% of the cardiac cycle, and then in the anterior cervical subarachnoid space. In healthy subjects ventricular CSF systole and diastole are constantly slightly out of phase with CSF systole and diastole in the subarachnoid space (Barshes et al. 2005). Arterial expansion causes brain movement and expansion of the central and lower parts of the brain acts as an expanding and retracting piston, which causes the CSF pulsation at the foramen magnum. Based on observations that CSF pulse pressure varies with cardiac and respiratory cycles it was concluded that CSF pulsation is due to changes in brain blood volume caused by arterial expansion (Sakka et al. 2011). The arterial expansion starts 100 ms after the R-wave in the ECG complex and has a fixed duration of about 300 ms. The brain expansion 40 23 Anatomy & Physiology starts 60 ms later than the arterial one and occupies half of the cardiac cycle, i.e. 400–500 ms. Of outmost importance to intracranial dynamics is the direct volume conduction of the pulse wave from the expanding extracerebral arteries to the veins and spinal canal (Sakka et al. 2011). the total volume of the four main intracranial components i.e. the brain, the CSF, the arterial and the venous blood, is constant and that any volume increase in one component causes a matching decrease in the other components so The systolic expansion of the intracranial arteries is thus balanced by a matching expulsion of CSF through the foramen magnum and expulsion of blood from the veins into the dural venous sinuses. The systolic volume increase of the brain is about 0.03 ml. The minute brain expansion occurs inwards towards the ventricular system and equals the systolic stroke volume in the aqueduct (0.03 ml/beat) (Bradley 2014). 24 41 Clinico-pathology of HII under high pressure and turbulence through smooth walled venous stenoses related to transverse sinus collapse from high CSF pressure (Farb et al. 2003). Ophthalmoscopic examination Papilledema, optic disc edema due to increased intracranial pressure, is the cardinal sign of BIH. Optic disc edema either directly or indirectly is the cause of visual loss of BIH. The higher the grade of the papilledema, the worse the visual loss is. But, in the individual patient, the severity of visual loss cannot accurately be predicted from the severity of the papilledema. A partial explanation for this is that with axonal death from compression of the optic nerve, the amount of papilledema decreases (Scott et al. 2010). 42 39 Clinico-pathology of HII Frisén (table 2) has proposed a useful staging scheme for papilledema with good sensitivity and specificity based on the ophthalmoscopic signs of disturbed axoplasmic transport. It has been modified recently with a key finding added for each stage or grade (Frisén 1982). Table 2: Frisén papilledema scale. Stage 0 Normal Optic Disc (figure 11) • Blurring of nasal, superior and inferior poles in inverse proportion to disc diameter. • Radial nerve fiber layer (NFL) without NFL tortuosity • Rare obscuration of a major blood vessel, usually on the upper pole Stage 1 - Very Early Papilledema (figure 12) • Obscuration of the nasal border of the disc • No elevation of the disc borders • Disruption of the normal radial NFL arrangement with grayish opacity accentuating nerve fiber layer bundles • Normal temporal disc margin Subtle grayish halo with temporal gap (best seen with indirect ophthalmoscopy) • Concentric or radial retrochoroidal folds. Stage 2 - Early Papilledema • Obscuration of all borders Elevation of the nasal border • Complete peripapillary halo. Stage 3 - Moderate Papilledema • Obscurations of all borders • Increased diameter of optic nerve head • Obscuration of one or more segments of major blood vessels 43 Clinico-pathology of HII leaving the disc Stage 4 - Marked Papilledema (figure 13) • Elevation of the entire nerve head • Obscuration of all borders Peripapillary halo • Total obscuration on the disc of a segment of a major blood vessel Stage 5 Severe Papilledema • Dome-shaped protrusions representing anterior expansion of the optic nerve head • Peripapillary halo is narrow and smoothly demarcated • Total obscuration of a segment of a major blood vessel may or may not be present • Obliteration of the optic cup. 44 Clinico-pathology of HII crania l nerve s that make nearly a 90° bend (CN II, VI, VII) appea r to be susce ptible to dama ge at Figure 13: Stage IV papilloedema. the site of the Ocular motility disturbances bend Horizontal diplopia is reported by about 1/3 of BIH (Ache patients and sixth nerve palsies are found in 10-20%. son Motility disturbances other than sixth nerve palsies have 2006) been . reported. Some of these reflect erroneous conclusions from the small vertical ocular motor imbalance that is known to accompany sixth nerve palsies. Bell's type palsies of CN VII rarely occur and are usually transient. The common thread here is that the 45 OF ABBREVIATIONS 2D-TOF: Two-dimensional time-off light 3D-PC: Three-dimensional phase-contrast ANA: Antinuclear antibody ANCA: Antinuclear cytoplasmic antibodies BMI: Body Mass Index cd/m2: candle/ meter square CSF: Cerebrospinal fluid CT: Computed tomography cVEP: conventional visual evoked potential CVST: Cerebral venous sinus thrombosis EDI: Electro-Diagnostic Imaging EEG: Electroencephalography ESR: Erythrocyte sedimentation rate FSH: Follicular stimulating hormone g/dl: gram/decilitre HVF: Humphrey Visual Field ICHD: International Classification of Headache Disorders ICP: Intracranial pressure IIH: Idiopathic intracranial hypertension 46 I ION: Ischemic optic neuropathy ISCEV: International society of clinical electrophysiology of vision LH: Luteinizing hormone mfERG: multifocal electroretinogram mfVEP: multifocal visual evoked potential MRI: Magnetic resonance imaging MRV: Magnetic Resonance venography NSAID: Non-steroidal anti-inflammatory drugs OD: oculus Dexter (the right eye) ON/MS: Optic neuritis/Multiple sclerosis ONSD: Optic nerve sheath distension OS: oculus Sinister (the left eye) OSA: Obstructive sleep apnea PCO: Polycystic ovary syndrome TS: transverse sinus TSH: Thyroid stimulating hormone TVOs: Transient visual obscurations VA: Visual acuity 47 II Idiopathic Intracranial Hypertension Idiopathic Intracranial Hypertension Historical Background: Idiopathic intracranial hypertension is the most recent of a number of names for the clinical syndrome of elevated intracranial pressure, without enlargement of the cerebral ventricles and in the absence of space occupying lesions. The German physician Heinrich Quincke published what is widely regarded as the first description of the condition, calling it „meningitis serosa ‟. This appeared to be preceded by case reports describing the same condition as early as 1866 (Johnston et al, 2007). By the turn of the 20th century, the terms serous meningitis and pseudotumour cerebri had been adopted, but diagnosis relied on clinical features or post mortem findings. Cerebral pneumography permitted further study of the condition in live patients and this was later to be enhanced by ventriculography and encephalography (Davidoff, 1965). The term benign intracranial hypertension was used for many years until several reports of severe visual loss in the condition rendered the term „benign‟ inappropriate (Foley, 1955). However, in view of the potential for devastating loss of vision associated with papilledema, Corbett and Thompson removed the adjective “benign” and substituted “idiopathic.” Idiopathic intracranial hypertension denotes the condition of increased ICP without an obvious underlying brain pathological condition (Corbett and Thompson, 1989). 4 48 Idiopathic Intracranial Hypertension Definition: Idiopathic intracranial hypertension is a syndrome of increased intracranial pressure (ICP) without ventriculomegaly or mass lesion, and with normal cerebrospinal fluid composition (Bandyopadhyay, 2001). With the advent of complex neuro-radiology, it has been possible to identify intracranial lesions and vascular pathologies in patients who might previously have been labelled as having IIH by one of its many names (Friedman and Jacobson, 2002). Older reports were likely to have included patients in whom cerebral venous sinus thrombosis (CVST) had not been excluded since imaging techniques were in their infancy. The clinical presentation of CVST is identical to that of IIH, but the outcome and management is dramatically different and CVST carries a significantly worse prognosis. It is essential that CVST is excluded before a diagnosis of IIH is made (Friedman and Jacobson, 2002). The diagnostic criteria have undergone several modifications over the years. Strict criteria now exist to ensure that a diagnosis of IIH is only applied to patients in whom all other causes of intracranial hypertension have been excluded (Friedman and Jacobson, 2002). These are shown in table (1) and are often referred to as „modified Dandy criteria‟ (Friedman and Jacobson, 2002). 5 49 Idiopathic Intracranial Hypertension Table (1): Diagnostic criteria of idiopathic intracranial hypertension „modified Dandy criteria‟ (Friedman and Jacobson 2002) 1. If symptoms and / or signs are present, they may only reflect those of generalised intracranial hypertension or papilledema with no localizing signs except an abducens nerve palsy. 2. Intracranial pressure, as measured in the lateral decubitus position, is elevated at least 25 cm H2O. 3. The composition of the cerebrospinal fluid is normal 4. There is no evidence of hydrocephalus, mass, structural or vascular lesion 5. Normal brain imaging that does not identify a cause for elevated ICP Despite widely accepted criteria, controversy still surrounds the definition of IIH as a discrete clinical entity. Pseudotumour cerebri syndrome is still used by many to describe patients with the condition, as an „umbrella‟ term that can include those cases where a causative factor is strongly suspected (Johnston et al., 2007). Nomenclature: The nomenclature for IIH remains controversial. “Benign intracranial hypertension” is no longer accepted, as significant visual morbidity may occur with this disorder (Corbett et al., 1982). The term “pseudotumour cerebri,” a historically popular and allencompassing term, leaves the impression that IIH is not a real disease. IIH is the favored term for the primary (idiopathic) disorder (Wall and George, 1991). 6 50 Idiopathic Intracranial Hypertension Epidemiology: • Incidence: Early attempts to measure the incidence of IIH, or the syndrome by one of its alternative names, are likely to have overestimated the number of cases, due to the inclusion of intracranial hypertension secondary to venous sinus thrombosis or other conditions difficult to elicit by older investigative techniques. In addition, most of the largest studies of incidence were completed prior to the widespread acceptance of the modern diagnostic criteria so the actual incidence of „truly idiopathic‟ IIH is by no means certain (Friedman and Jacobson, 2002). Around the world, a small number of population studies have attempted to measure the overall incidence (table 2). Table (2): Number of population studies to measure the overall incidence of IIH (Kesler et al., 2001 and Raoof et al., 2011) Year Location Author Population IIH Incidence per 100,000 0.9 1.07 1988 Iowa, USA Durcan et al. (1988) size 2,913,808 1988 Louisiana, USA Durcan et al. (1988) 4,480,681 1993 Benghazi, Libya Radhakrishnan et al. 519,000 2.2 2000 Hokkaido, Japan (1993) Yabe et al. (2000) 5,780,000 0.03 2001 Belfast, Ireland Craig et al. (2001) 1,640,000 0.6 2011 Sheffield, UK Raoof et al.(2011) 3,520,000 1.56 7 51 Idiopathic Intracranial Hypertension • Gender and age distribution: Idiopathic intracranial hypertension occurs most commonly among women. The prevalence is approximately 1 case/100,000 women but increases to 13 cases/100,000 women of ages 20 to 44 years who are 10% above ideal body weight and 19 cases/100,000 women of ages 20 to 44 years who are obese (20% above ideal body weight) (Durcan et al, 1988). Men are affected less frequently. The incidence is 0.3 cases/100,000 men but increases to 1.5 cases/100,000 obese men(20% above ideal body weight).Female-to-male ratios range from 4.3:1(Durcan et al, 1988) to 11.5:1(Mezaal and Saadah, 2005). Idiopathic intracranial hypertension is predominantly a disease of younger adults. In one major study, 59% of patients were in the third decade of life at diagnosis, (Durcan et al, 1988) and mean ages at onset of symptoms have been reported by others as 29 (Craig et al, 2001), 31 (Wall and George , 1991), 35 (Galvin and Van Stavern, 2004) and 36 years (Mezaal and Saadah, 2005). Idiopathic intracranial hypertension may also be observed in the pediatric population. A Canadian study of children demonstrated equal incidence among boys and girls, of approximately 1 case/100,000 individuals (Baker et al, 1985). 8 52 Idiopathic Intracranial Hypertension > Etiological factors and related conditions: 1. Genetic: Isolated familial cases raise the possibility of a genetic component in the disorder, but no linkage studies have been performed to date (Mokri, 2001). 2. Obesity: The evidence linking IIH and obesity is conclusive. Even moderate weight gain appears to be associated with IIH. Patients with Body Mass Index (BMI) of 25-30 had an increased risk of IIH in a USA case-control study, although higher categories of BMI were associated with progressively greater risk of the condition (Daniels et al, 2007). In the same study, 29% of patients reported no gain in weight and it is important to note that IIH does occur in people who have normal or even low body mass (Daniels et al, 2007). Obesity is present in up to 94% of women and about 60% of men with IIH (Wall and George, 1991), one of the proposed mechanisms relating obesity to IIH are central obesity that raises cardiac filling pressures. This rise in pressure leads to impeded venous return from the brain (due to the valveless venous system that exists from the brain to the heart) with a subsequent elevation in intracranial venous pressure. If not treated appropriately, chronic interruption of the axoplasmic flow of the optic nerves with ensuing papilledema due to this pressure may lead to irreversible optic neuropathy (Daniels et al., 2007), also increased intraabdominal pressure that pushes the diaphragm superiorly and raises the pleural pressure which then impede venous return from the brain leading to 9 53 Idiopathic Intracranial Hypertension vascular engorgement and sustained increase of intracranial venous pressure (Sugerman et al., 1997). Obesity alone has been strongly associated with a chronic inflammatory state, characterized by increased adipose-tissue production of tumor necrosis factor-α and other proinflammatory “adipokines” associated with increased expression of prothrombotic genes such as plasminogen activator-inhibitor-1 and concentrations of lipoprotein (a) and estrogens, each of which has the independent prothrombotic effect of increasing the levels of several clotting factors (Trayhurn and Wood, 2004). 3. Vitamin A: Excessive dietary intake of vitamin A has been associated with raised intracranial pressure. Historical narratives of Polar Eskimos and their dogs suffering from the clinical features of intracranial hypertension, including headache and prostration, after ingesting large quantities of liver from polar bears were later linked to the high levels of vitamin A in the organ (Fishman, 2002). Significantly heightened concentrations of retinol have been reported in the CSF but not serum of patients with IIH compared with controls (Tabassi et al., 2005). 4. Medications: Case reports have implicated several drugs in intracranial hypertension. Table (3) shows several drugs related to IIH. (Weese-Mayer et al., 2001) 10 54 Idiopathic Intracranial Hypertension Table (3): Several drugs implicated in intracranial hypertension. (Weese-Mayer et al; 2001) Tetracyclines Nitrofurantoin Nalidixic acid Sulfamethoxazole Penicillin Corticosteroid treatment and withdrawal NSAID in Bartter‟s syndrome Mesalamine Lithium carbonate Amiodarone Chlordecon Ciclosporine NSAID: non-steroidal anti-inflammatory drugs. 5. Menstrual Dysfunction : A history of menstrual irregularities does appear to be more common in IIH than in unaffected females. In one questionnaire study of 40 IIH patients, a change in menstrual pattern just prior to diagnosis was more frequently reported than in the reference period in 39 controls (Ireland et al., 1990). Larger studies have listed menstrual dysfunction amongst reported symptoms, but there has been no published evidence of specific hormone dysfunction to explain these findings and it is worth noting that obesity itself is known to be associated with menstrual irregularities (Glueck et al., 2005). 11 55 Idiopathic Intracranial Hypertension 6. Pregnancy: Pregnancy is occasionally associated with idiopathic intracranial hypertension. This disorder can present at any stage of pregnancy (Friedman and Jacobson, 2004). A retrospective case control study and literature review concluded that the apparent association with pregnancy reflects the age and gender of the typical patient with IIH (Digre et al., 1984). Further rigorous investigation has failed to show any statistically significant relationship, with similar pregnancy histories amongst IIH patients and matched controls (Ireland et al., 1990). 7. Polycystic Ovary Syndrome: Polycystic ovary syndrome (PCOS) appears to occur with increased frequency in IIH. In the study by Glueck et al.2005 37 (57%) of the 65 women with IIH were found to meet the diagnostic criteria for the syndrome. Whilst this would appear to represent a much higher prevalence of PCOS than that of the general population, the high levels of obesity in both IIH cohorts and the lack of reliable data on the incidence of PCOS amongst a similarly obese population make conclusions difficult to reach (Glueck et al., 2005). 8. Sleep Disorders: Sleep apnea syndrome (OSA) is also prevalent amongst an obese population, but several papers have linked it with IIH (Purvin et al., 2000). It remains unclear whether there is a disease association between OSA and IIH, or if OSA plays a causative role in the condition, such that 12 56 Idiopathic Intracranial Hypertension intracranial hypertension secondary to OSA is a separate clinical entity to „true‟ IIH (Bruce et al. 2009). 9. Anaemia : The diagnostic criteria for IIH specify severe iron deficiency anemia as a condition that can masquerade as IIH (Biousse et al, 2003). A retrospective consecutive case series at the Birmingham and Midland Eye Centre, UK, between 2005 and 2007 of 107 new cases of IIH according to strict diagnostic criteria found six instances of microcytic anaemia, with haemoglobin levels below 10.2g/dl(gram/decilitre) (Mollan et al, 2009). The prompt resolution of symptoms and improvement in visual function upon correction of the haematological abnormality in all cases was highly suggestive of an association between anaemia and raised intracranial pressure. Testing patients who present with signs of IIH to exclude anaemia is recommended (Mollan et al, 2009). 10. Co-morbid Conditions: Systemic arterial hypertension has been reported as occurring in 14 to 32% of patients with IIH (Galvin and Van Stavern, 2004). In one study, blood pressure was significantly higher amongst people with IIH than matched controls (Ireland et al, 1990). Other co-morbid conditions associated with IIH include diabetes mellitus, thyroid disease, hypoparathyroidism, stroke, chronic migraine, ulcerative colitis and systemic lupus erythematosus (Galvin and Van Stavern, 2004). There are published examples of apparent IIH occurring in patients with a variety of other conditions, including hepatitis A (Thapa et al, 13 57 Idiopathic Intracranial Hypertension 2009a) and E (Thapa et al, 2009b), transplanted kidneys (Durcan et al, 1988) , leukaemia (Vartzelis et al, 2009) and the lysosomal storage disease cystinosis (Dogulu et al, 2004). Clinical features: > Headache : Headache has consistently been shown to be the most common symptom of IIH, occurring in 68 to 98% of patients (Kesler and Gadoth, 2001). It appears to be less common amongst children with the condition, who may frequently present with other signs such as irritability or visual failure (Lim et al, 2004). A cohort study of 82 patients with IIH was performed and found 68% meeting the diagnostic criteria for primary headache as defined by the International Classification of Headache Disorders, ICHD-1. The headaches were divided as tension-type in 30%, migraine without aura 20%, chronic tension-type headache 10% and analgesia overuse in 8% (Friedman and Rausch, 2002). Isolated cases of cluster headache in association with IIH have also been reported (Testa et al, 2008). A further study showed ocular pain to be a much more predominant feature in patients with IIH than controls (Daniels et al, 2007). Quite often, 14 58 Idiopathic Intracranial Hypertension headache may be the only presenting symptom (Galvin and Van Stavern, 2004). > Papilledema : Disturbance of vision is the second most prevalent symptom of IIH. Visual symptoms usually accompany headache, but may occur in isolation (Galvin and Van Stavern, 2004). Papilledema is almost a universal finding in IIH and its absence should cause the diagnosis to be questioned (Mackenzie and Cioffi, 2008). Papilledema, ranging from mild to severe, with or without hemorrhages, is widely regarded as the hallmark of idiopathic intracranial hypertension. Atypical cases are described in the adult literature where papilledema could be asymmetrical, unilateral, or even absent (Wraige et al, 2002). However, Idiopathic intracranial hypertension without papilledema is a known condition in adults and usually presents with clinical features resembling chronic daily headaches or migraine (Wraige et al, 2002). A variety of symptoms are reported, including blurring secondary to papilledema, double vision, field defects and short-lived visual abnormalities such as Transient visual „obscurations (Kesler and Gadoth, 2001): a. Visual Acuity(VA) : The refracted visual acuity is often normal when tested in patients with IIH. Reduced central visual acuity does occur, but review of the literature suggests this to be the case in less than a quarter of patients at presentation (Craig et al., 2001). 15 59 Idiopathic Intracranial Hypertension b. Visual Field Defects: Testing of visual fields by confrontation in patients with IIH may elicit few abnormalities, but formal perimetry reveals that visual field defects are often present and enlargement of the blind spot is nearly always seen. In general, visual field abnormalities are one of the earliest indicators of ophthalmic disease (Galvin and Van Stavern, 2004). The visual field defects in papilloedema mirror those of other anterior optic nerve pathologies, such as glaucoma and anterior ischaemic optic neuropathy. Enlargement of the physiological blind spot is seen in most cases of IIH, related to the effect of the swollen optic nerve head occupying a larger area of retina (Figure 1). Often fields in IIH with blind spot enlargement are categorised with normal fields, unless they encroach on fixation, due to the benign and common nature of the finding. The locations of other visual field defects in IIH reflect the retinal nerve fibre arrangement and its relation to swollen areas of the optic disc. Of these „disc-related‟ defects, peripheral rim constriction appears to be the most common (Figure 2). Inferonasal steps are the next most common (Figure 3), then arcuate scotoma, arch-shaped defects in the field of vision as well as nasal defects (Galvin and Van Stavern, 2004). Other less common defects include central, paracentral and caecocentral scotomata, with temporal and altitudinal losses even less frequently recorded (Wall and George, 1991). (Figure 4) 16 60 Idiopathic Intracranial Hypertension Figure (1): Goldmann fields with minor enlargement of the blind spot as the only abnormality (Galvin and Van Stavern, 2004) Figure (2): Visual field (Goldmann perimetry) from the right eye of a 54 years female with IIH showing marked constriction (Galvin and Van Stavern, 2004) 17 61 Idiopathic Intracranial Hypertension -3 -10 -7 -6 -7 -12 0 -1 -8 -9 2 -5 -3 -4 -2 1 i 0 -3 -5 -2 -3 -3 -2 -4 -1 -i -4 -5 -5 -5 -11 -5 -2 -4 -5 -3 -3 -9 -9 -3 0 -2 -3 -1 0 -6 -12 "11 -8 -4 -7 -2 -5 -12 -9 -8 -6 -2 -5 0 -3 -10 -15-13-2 -3 -4 -4 -5 -1 -2 -2 -3 -5 -2 -1 -3 0 1 0 -6 -4 -2 -5 -7 -9 -4 -4 -21 -21 -1 -13-11 0 0 -7 -2 -2 -2 -8 -19-19 Total Pattern Deviation Deviation - » ■' 3& - &I 8IISI II I» & 8 8 • »£8 ■ 8I 1 ££ ■ • • 8 £ :: ■8 ■ ■ £ • • ■ : : 8 ■ £ ■■ ■ S ■■ • • £ " £ • & • • 8 ■I -I : : < 5% £ & < 2% 8 < 1% ■ < 0.5% Figure (3): Visual fields (Humphrey 24-2 automated static perimetry) from the right eye of a woman with IIH. Generalised reduction in sensitivity with enlargement of the blind spot and an inferonasal defect are shown. 1.7a: Visual thresholds as shown by greyscale diagram and numerical results; 1.7b: Numeric and symbolic representations of the calculated total and pattern response deviations from normal. (Galvin and Van Stavern, 2004) 18 62 Idiopathic Intracranial Hypertension Figure (4): Examples of less common visual field defects in IIH (Wall and George, 1991) c. Transient visual obscurations(TVOs): Transient visual obscurations variously described as shadows, dark patches or black spots in the field of vision, affecting one or both eyes and resolving after a few seconds or minutes (Kesler and Gadoth, 2001). 19 63 Idiopathic Intracranial Hypertension They may occur with changes in posture. Both the exact pathophysiology and the prognostic significance of transient visual obscurations remain unknown (Schirmer and Hedges, 2007). However it was said that the underlying mechanism for visual obscurations appear to be transient ischemia of the optic nerve head consequent to increased tissue pressure (Sadun et al., 1984). Additional Signs It is a requirement of the diagnostic criteria for IIH that neurological examination is normal except for the presence of signs reflecting generalised intracranial hypertension and papilloedema (Friedman and Jacobson, 2002). Unilateral or bilateral sixth cranial nerve palsies can therefore be expected and have been specifically documented in some studies at rates of 17 to 33% (Mezaal and Saadah, 2005). Abducens palsies are more likely to be unilateral and appear to be more common amongst children (Johnston et al., 2007). Other cranial nerve defects have been reported very rarely, in single case reports, including facial and oculomotor palsies (Capobianco et al., 1997). 20 64 Idiopathic Intracranial Hypertension Investigations: The diagnosis may be suspected on the basis of the history and examination. To confirm the diagnosis, as well as excluding alternative causes, several investigations are required as fundus examination & magnetic resonance imaging (MRI); more investigations may be performed if the history is not typical or the patient is more likely to have an alternative problem : children, men, the elderly, or women who are not overweight (Gonzalez et al., 2009). I. Laboratory tests: a) Blood tests: Blood tests are done to rule out systemic lupus erythematosus or other collagen-vascular disease, since these have been reported as underlying conditions in some patients who present with idiopathic intracranial hypertension (Nampoory et al., 1997). Some authors advocate screening for anti-cardiolipin antibodies and other procoagulant states in all patients with IIH who are either male or nonobese (Sussman et al., 1997). b) CSF studies: Examination of CSF pressure in patients with suspected IIH is mandatory and lumbar puncture is a safe procedure in the fully conscious patient with no focal neurological deficit and normal brain imaging, even in the presence of papilledema (Bono et al., 2002). Lumbar puncture is performed to measure the opening pressure (levels above 25cmH2O is diagnostic), as well as to obtain CSF to exclude alternative diagnoses. If the opening pressure is increased, CSF may be 21 65 Idiopathic Intracranial Hypertension removed for relief. The CSF is examined for abnormal cells, glucose and protein levels; in IIH, all are within normal limits (Friedman and Jacobson, 2004). Occasionally, the pressure measurement may be normal despite very suggestive symptoms. This may be attributable to the fact that CSF pressure may fluctuate over the course of the day. If the suspicion remains high, it may be necessary to perform more long-term monitoring of the intracranial pressure by a pressure catheter (Friedman and Jacobson, 2004). There are several issues surrounding the criteria of the measurement and limits of the opening pressure. Whether the patient is supine, prone, or sitting, one must be sure that the reference level for measurement is the level of the left atrium. It is essential that the patient is as relaxed as possible and time should be allowed for the pressure to stabilise. The knees and hips should be in the extended position during pressure recording, since there is evidence that a flexed posture as well as the Valsalva manoeuvre can elevate the pressure. Spuriously high values can occur with Valsalva maneuver and the hypoventilation associated with sedation (Neville and Egan, 2005). II. Radiological Studies: a) CT scan: Computed tomography (CT) was the investigation of choice until it was superseded by MRI. Computed tomography is adequate to rule out larger tumors or lesions, but it is not as sensitive as MRI for meningeal infiltration and/or dural venous sinus thrombosis. In IIH these scans may be normal, although small or slit-like ventricles (Brodsky and Vaphiades, 1998). 22 66 Idiopathic Intracranial Hypertension b) Brain Magnetic Resonance imaging: Although there are no pathognomonic radiological signs in the disorder but certain markers of raised intracranial pressure in patients with idiopathic intracranial hypertension can be detected as follows: • Flattening of the posterior sclera (80%): In a retrospective study of imaging features that have been suggested as typical for patients with IIH, only flattening of the posterior globe was found statistically to be a reliable indicator of IIH, with a specificity of 100% and a sensitivity of 43.5% (Agid et al, 2006). • Empty sella (70%): The mechanism by which an empty sella develops in patients with idiopathic intracranial hypertension is intrasellar herniation of CSF and arachnoid membrane through an absent or open diaphragma sellae in association with increased intracranial pressure. The pituitary gland is flattened and distorted. The infundibulum is midline and extends down to the floor of the sella turcica (Laura et al, 2005). • Optic nerve sheath distension (ONSD): The intraorbital part of the sheath, and particularly its retrobulbar segment, can distend when ICP is elevated. MRI can be used to measure precisely the diameter optic nerve and its surrounding sheath, by using a fatsuppressed T2-weighted sequence (Lam et al, 1997). However, papilledema is a delayed consequence of chronic CSF accumulation in the retrobulbar optic nerve dural sheath due to raised 23 67 Idiopathic Intracranial Hypertension pressure in CSF in cranial cavity, and direct measurement of such CSF accumulation may provide an earlier and more responsive measure of intracranial hypertension. Optic nerve sheath distension could therefore be an earlier, more reactive and more sensitive sign of raised ICP. High-resolution MRI is accurate at measuring ONSD (Weigel et al, 2006). • Prelaminar enhancement of optic nerves. • Enhancement of the optic nerve distension of the perioptic subarachnoid space. • Intraocular protrusion of the prelaminar optic nerve. • Vertical tortuosity of the orbital optic nerves. (Brodsky and Vaphiades, 1998) c) Magnetic Resonance venography (MRV): Different MRV sequences offer the capability of investigating cerebral sinovenous outflow from multiple orientations. Two-dimensional time-offlight (2D-TOF) and three-dimensional phase-contrast (3D-PC) techniques, that do not require contrast injections, have been widely used for MRV imaging (Bono et al, 2003). Sagittal T1-weighted images often provide excellent views of the superior sagittal sinus, and these typically are included in routine MRI. Extraluminal narrowing of the transverse sinuses may be a typical feature of IIH as reported (Farb et al; 2003). 24 68 Idiopathic Intracranial Hypertension Bilateral transverse sinus (TS) narrowing in patients with idiopathic intracranial hypertension can be found regularly on MR imaging and may cause venous outflow obstruction. Transverse sinus stenosis mostly consisted of a long smooth tapered narrowing of the venous conduit. A minority had intraluminal filling defects, which were attributed to a possible swelling of arachnoid granulation (Farb et al, 2003). Thrombosis of the cerebral venous circulation can present with an identical clinical picture to IIH (Biousse et al, 1999) .Thus to comply with recent diagnostic criteria, cerebral venous sinus thrombosis must be excluded (Friedman and Jacobson, 2002). ■ Visual evoked potentials (VEP): Clinical visual impairment in IIH is probably preceded by prolongation of VEP responses and the latter may be evidence of optic nerve dysfunction due to demyelination (Kesler et al, 2009). 69 I. Non-surgical management This includes weight reduction, medical treatment and serial lumbar punctures.139 A. Weight reduction As obesity and/or recent weight gain are the main identifiable IIH risk factors in most patients, a defined weight loss program should be initiated regardless of disease severity. Observation without medical or surgical intervention may be indicated in an asymptomatic patient who presents with papilledema and understands the importance of clinical monitoring for progression. The precise relationship between weight gain or obesity and raised ICP is not clear, but the benefits of weight reduction have been demonstrated repeatedly. In a study of 25 obese women, weight reduction was associated with reduction of headaches, papilledema, and ICP.141 In addition, in individuals whose IIH is in remission, prevention of weight fluctuation has been shown to be critical in prevention of recurrence.142 Studies have demonstrated that loss of approximately 6% of body weight is associated with a reduction in papilledema and discontinuation of systemic treatment.5 To most effectively assist a patient in weight loss, the help of a registered dietician or nutritionist should be enlisted. If weight loss through diet and exercise fails, bariatric surgery has been shown to positively benefit IIH, although this is clearly more invasive and carries risks of anastomotic leaks, small bowel obstruction, mal-absorption, and gastrointestinal bleeding. B. Serial lumbar punctures Assuming a normal rate of CSF production in IIH (and there is no evidence to the contrary), the theoretical objection to serial lumbar punctures as treatment is that volumes around 20-30 ml will be restored in a very short time so, unless some other factor is operative, there will not be a sustained reduction in CSF pressure. It has been suggested that repeated punctures may create a leak, even a fistula, at the puncture site(s) which can produce the required sustained effect. Such a leak must be considered as unpredictable, both in its occurrence and its presumed effect. There is also the possibility that reduction of CSF pressure by drainage might favourably influence a cycle of events involving venous sinus collapse. On present evidence, the most that can be said is that a small percentage of cases of IIH do show resolution on treatment with repeated lumbar punctures, but how much this is due to the punctures themselves is an unresolved issue. 70 Further, the treatment is distressing to the patients so, given the other options available, the method is no longer applicable. If sustained drainage of CSF is thought to be desirable, it should more effectively be achieved by continuous drainage via any mean of chronic CSF diversion.139 C. Medical treatment Medical treatment is indicated in the setting of good vision when a patient’s primary symptom is headache. It includes analgesics for symptomatic relief of headache, Carbonic anhydrase enzyme inhibitor (Diamox©), steroids and others.139 i. Analgesics Symptomatic therapy is often necessary even in the setting of preventative medication use in order to treat acute "break-through" headaches. The use of acute symptomatic therapy should be limited to no more than 2 days per week, as more frequent use raises the risk of medication overuse headache (MOH). Standard acute therapies can be used in conjunction with preventative therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) such as naproxen and indomethacin can be used for both migraine and tension-type headache. There is some evidence that ind omethacin (Dosage: Initially 50 mg IV, followed by oral maintenance dose of 75 mg/day) also helps to lower ICP, making it a good choice in this population. The ICP-lowering effects of indomethacin can be explained best by vasoconstriction and a consecutive reduction of the cerebral blood flow (CBF). After IV administration of indomethacin there is a significant increase in the arterio-venous oxygen difference. Several studies have shown that indomethacin does not cause cerebral ischemia, because the cerebral metabolic rate of oxygen or the net production of lactate does not significantly change after IV administration. In healthy volunteers auto-regulation is preserved, because the vasoconstrictive effects of indomethacin are still influenced by hypoxemia and hypercapnia. Indomethacin does not influence the effects of other standard therapies for ICP control, but it does cause a rebound increase in ICP after drug discontinuation.143 ii. Carbonic anhydrase enzyme inhibitors (CAIs) Acetazolamide clearly has a role in the management of IIH and might legitimately be regarded as the first line of medical treatment. Although, as with other methods of treatment for IIH, there is no definitive study of the use of the drug, the impression from available reports is that it is likely to be effective in approximately 20-40% of cases with a greater 71 particularly if there is a causative factor for chance of success in children and adult males, the IIH which can be withdrawn or corrected. Acetazolamide is generally well tolerated with 72 a low incidence of side effects and is suitable for prolonged use if the clinical situation so dictates. Some patients are intolerant of acetazolamide, however, and in all cases regular assessment of blood electrolyte levels is advisable.139 Acetazolamide (Diamox©) and Methazolamide (Neptazane©) inhibit carbonic anhydrase in the choroid plexus, ostensibly decreasing CSF production. They also act as mild diuretics. Acetazolamide in adult patients is usually started at 1 g daily (250 mg QID or 500 mg BID); with a maximum recommended daily dose of 4 g. Side‑effects include paraesthesia, lethargy, and altered taste and may limit dosage.144 Whether it is better to use acetazolamide alone or in combination with other treatments such as lumbar punctures, steroids, other diuretics or even cardiac glycosides is an unresolved question. Topiramate is an alternative carbonic anhydrase inhibitor which has recently been tried in some patients with IIH. It is approved for the treatment of epilepsy and migraine prophylaxis and also causes anorexia which has merit for many patients with IIH.139 iii. Diuretics Although non‑CAI diuretics (i.e. furosemide, chlorthalidone, and spironolactone) have been used in the treatment of IIH, their efficacy in reducing ICP is unclear. Hypokalaemia may occur with any of these agents, and blood electrolytes should be monitored.144 A very little can be said about the use of diuretics other than acetazolamide in the treatment of IIH. There are clearly some cases in which they will be successful, and resolution has been reported with ‘standard’ diuretics, particularly chlorothiazide, frusemide and with osmotic diuretics such as glycerol and urea. There is, however, no evidence from which to draw any conclusions about their relative merits, either with respect to each other or with respect to other treatment methods.139 iv. Steroids Beginning with the report by Paterson et al. in 1961, steroids (prednisone, prednisolone, methylprednisolone, betamethasone, and dexamethasone) were, for a time, the first choice treatment for IIH in a number of centres. There was also, during this time, an increasing awareness of the complicated relationship existing between IIH and steroids since not only did steroids appear effective in treatment but also there were reports of cases of IIH occurring in patients being treated with steroids for other conditions, particularly during staged withdrawal of the agent.145 Johnston et al. reported 7 cases of IIH treated with steroids and documented CSF pressure before treatment and 3months after the start of the therapy. All patients had their intracranial 73 pressure evaluated by continuous monitoring before, during, and after treatment. 74 All seven patients were completely free of symptoms and signs at 3 months. Despite this, the CSF pressures, which were essentially unchanged at 1 week, were still above normal at 3 months (Fig.29), although there was a significant reduction (pre-treatment mean 27.2 mmHg, SD 5.7; 1-week mean 27.3 mmHg, SD 4.0; 3-month mean 21.2 mmHg, SD 6.5).139 Before treatment 1 month after VV^%A^Vv^^Av- 'yifl^/^hf^ 1 1 20 1 40 20 40 Time (min) Figure 29: CSF pressures of one of the 7 patients before and one month after treatment course of steroids.72 In summary, there is undoubtedly a moderate recurrence rate for IIH after steroid treatment (probably between 10 and 20%), and a definite incidence of complications some of which are of a serious nature. Steroids are probably more effective in combination with either acetazolamide or serial lumbar punctures, or both, although there are no properly conducted studies to support this impression. In the uncommon cases of IIH occurring during withdrawal of steroids being administered for an unrelated condition, restoration of a higher dose of steroids followed by a more gradual withdrawal is the primary treatment but this may have to be supplemented by another agent. Currently, however, the use of steroids is limited to cases of rapidly deteriorating vision including cases of cerebral venous thrombosis in combination with CSF drainage.139 v. Others There are several forms of medical treatment other than those already considered which have been used in small numbers of cases of IIH. These include cardiac glycosides, specifically digoxin, which has been shown experimentally to effect a 61-78% reduction in CSF production, an effect more pronounced than that of acetazolamide. This drug is it effective as a single agent but ineffective when used in conjunction with 75 diuretics. However, it has been disappointing in its very limited clinical use.146 76 There is also a report of the use of hyperbaric oxygen (HBO) in the treatment of IIH in eight cases. Each patient underwent HBO with 100% oxygen at 2 atmospheres absolute a day for 15 days. In all patients a gradual disappearance of signs and symptoms of elevated intracranial pressure was observed. No lasting effect of treatment was seen after concluding therapy. The effect of HBO in the treatment of IIH has not yet been clarified, but the results can encourage further experience and studies.144 25 77 78 LUMBO-PERITONEAL SHUNTING INDICATION: progressive visual failure from papilledema due to increased intracranial pressure and intractable generalized headaches. In this small subset patients who do not respond to conventional medical therapy. CONTRAINDICATIONS: The shunting procedure requires the introduction of a large 14-gauge Tuohy needle into the lumbar subarachnoid space. This may not be feasible in some clinical situations. Patients with advanced lumbar degenerative arthropathy with marked spinal stenosis have a very narrow spinal canal with crowding of cauda equina roots, and a spinal tap or the satisfactory advancement of the lumbar catheter may not be technically possible. Patients with an advanced degree of congenital kyphoscoliosis with rotational deformities may also present a similar problem. Achondroplastic dwarfs tend to have an extreme degree of narrowing of the spinal canal, and in such individuals a ventriculoperitoneal shunt may be the better alternative. Patients who have undergone multiple previous lumbar laminectomies for disc disease with documented evidence of adhesive arachnoiditis or with radiologic evidence of an extensive posterior midline fusion of the lumbar spine are not suitable candidates for lumbar-peritoneal shunting. Very small infants will not accommodate the 14-gauge needle that is required for the introduction of the catheter. Patients who have congenital anomalies in the lum-bosacral region, such as meningomyelocele, tethered cord syndrome, lipomeningocele, diastematomyelia, etc., are better treated by ventriculoperitoneal shunting. Patients with a Chiari malformation or aqueductal stenosis with hydrocephalus are also best treated by ventriculoperitoneal shunting. Patients with infection or skin breakdown in the lumbar area, with chronic infection from any cause, or with vertebral osteomyelitis or discitis are not suitable candidates for lumbarperitoneal shunting DESCRIPTION OF THE SHUNT SYSTEM: The main components of the lumbar-peritoneal shunt system are a lumbar catheter, a peritoneal catheter, a valve unit, a “stepdown” connector between the lumbar catheter and the valve unit, a straight connector between the valve unit and the peritoneal catheter, and a suture clamp. The Valve Unit : 79 The valve unit (Fig. 1, inset) provides controlled drain-age of the cerebrospinal fluid from the lumbar sub-arachnoid space into the peritoneal cavity while maintaining the intracranial pressure in the physiologic range. The valve has a unique bimodal design to compensate for varying hydrostatic pressures in the recumbent and upright positions. On the inlet side is the lower pressure mechanism consisting of a spring actuated ball-in-cone valve. The tension in the spring determines the valve opening pressure. On the outlet side is the higher pressure, gravity actuated mechanism consisting generally of three freely rolling steel balls. The combined weight of the balls determines the opening pressure. Figure 1. The lumbar-peritoneal shunt assembly in place. The valve unit is shown enlarged at the top (inset). In the horizontal position, only the lower pressure, spring actuated, ball-incone valve is functional. The spinal fluid, after it escapes out of the valve, simply flows by the steel spheres which are free to move and do not block the entry site into the high pressure mechanism. As the patient assumes an upright position, however, the steel balls gravitate down and block the entry site into the mechanism. For the fluid to flow now, it has to lift up the steel balls. In the upright position, both the spring actuated and gravity actuated mechanisms are functional; thus in the upright position, spinal fluid flow remains constant despite the higher hydrostatic pressure. The low and high pressure valves are housed in a clear silicone elastomer casing. The inlet tubing into the valve is clear and the outlet tubing is opaque. A color-coded band at the lower waist of the silicone casing indicates the pressure ranges of the horizontal and vertical valves (Table 1.) 80 An appropriate range of valve pressures should be chosen based on the ventricular size and the height of the patient (Table 1). The range of opening pressure for the horizontal valve is chosen based on the ventricular size. A lower opening pressure range (50-80 mm H2O) should be chosen for patients with extreme ventricular enlargement and a standard opening pressure range (85125 mm H2O) for patients with moderate ventricular enlargement. The opening pressure of the vertical valve is chosen according to the patient’s height. Tall adults with moderate ventricular enlargement will require valves with a higher opening pressure range (325-445 mm H2O). Average adults or tall children with moderate ventricular enlargement will require a standard opening pressure range (265-365 mm H2O). Lumbar Catheter The lumbar catheter is a narrow radiopaque silicone catheter with multiple small perforations at its distal end. The distal end is inserted into the lumbar subarachnoid space through a Tuohy needle and the proximal end is connected to the inlet side of the valve unit. Peritoneal Catheter The peritoneal catheter is of larger diameter than the lumbar catheter. It is also made of radiopaque silicone elastomer. Its proximal end is connected to the outlet side of the valve unit using a straight connector. The distal end has several staggered rows of slits which provide multiple routes of drainage but do not function as valves. “Stepdown” Connector The stainless steel stepdown connector is used to attach the lumbar catheter to the inlet side of the valve unit. The smaller side connects to the catheter and the larger side connects to the valve unit. Straight Connector The stainless steel straight connector is used to attach the peritoneal catheter to the outlet side of the valve unit. Suture Clamp A butterfly suture clamp made of silicone is used to anchor the lumbar catheter to the lumbo-dorsal fascia near the entry site of the catheter to prevent migration of the catheter during movements of the back (Fig. 3E). 81 PREOPERATIVE PREPARATION: A diagnostic workup should include brain imaging with an MRI or CT study to confirm the clinical diagnosis and to rule out obstruction within the ventricular pathways. A plain roentgenogram of the lumbar spine in the anteroposterior projection will rule out any local abnormalities that will contraindicate a lumbar puncture. In a patient who has undergone multiple previous abdominal procedures with significant abdominal adhesions, the help of a general surgeon may be sought to assist in the laparotomy component of the procedure. If the patient has had a recent diagnostic or therapeutic lumbar puncture, the operation should be delayed for at least three to five days so that during surgery the lumbar catheter is more likely to enter the subarachnoid space rather than the subdural space. If the clinical situation permits, it is best to readmit the patient a week to 10 days after the tap for the definitive surgical procedure. OPERATIVE TECHNIQUE : Anesthetic Considerations and Patient Positioning: I always use general anesthesia for this procedure. Good muscle relaxation will help during the laparotomy. The operation is always done in the lateral decubitus position (Fig. 2A). It can be either the right or the left lateral decubitus position depending on the surgeon’s preference. I generally use the right lateral decubitus position with the patient’s left side up. The patient is rolled over a soft egg crate mattress in the lateral decubitus position with the hip and knee flexed on the down side and extended on the up side. All the pressure points are additionally padded, especially those under the greater trochanter and the right arm. A rolled sheet is placed under the axilla to prevent compression of the axillary artery and vein. The free left arm is held over in a suspended arm rest as is generally used in thoracotomy procedures. The patient may lay over an inflatable bean bag mattress which helps to retain the lateral decubitus position throughout the procedure. The head should be supported on sheets or pillows to maintain its neutral position, in line with the spine. The chest and the knee are flexed to maximize the interspinous space but there should be sufficient room in front for laparotomy access. The back, flank, and abdomen are shaved, prepared, and draped. In patients in whom the CSF pressure is low, the operating table may be tilted into a head up position to promote good flow of CSF. 82 Figure 2. A, the lateral decubitus position used for lumbar-peritoneal shunting. B, lumbar puncture with a Tuohy needle. C, rotation of the needle by 90° to direct the bevel of the needle cephalad. Checking the Valve for Patency and One-way Flow: Before implantation of the valve unit, the valve patency and one-way flow mechanism should be checked, as follows. Patency: The valve unit is temporarily connected to the lumbar and peritoneal catheters. The inlet (lumbar) tubing is submerged in a sterile saline solution. A syringe is attached to the distal (peritoneal) end of the tubing through a blunt 18-gauge needle. Saline is slowly aspirated through the system, purging out all of the air. The syringe is then disconnected, and the distal end is allowed to hang freely. Patency is proven if saline drips from the distal end. One-way Flow Mechanism: After the valve unit and the catheters have been filled with saline in the manner described above, the valve is held vertically (with the arrow pointing down) and the distal end of the peritoneal catheter is elevated above the valve unit. Absence of fluid return through the proximal tubing for 80 seconds confirms an intact one-way flow mechanism. Introduction of the Lumbar Catheter: I generally do not make a lumbar incision before the insertion of the needle. In the unlikely event that the lumbar puncture is not successful, then one may have to go to a space higher or lower. Ordinarily, the lumbar puncture is performed at the L3-L4 or L4-L5 space. Standard anatomical landmarks are used (Fig. 2B). The top of the iliaccrest83 generally corresponds to the L4-L5 interspinous space. One should be cognizant of the fact that in the lateral decubitus position the spinous processes do not lie exactly in the midline between the paraspinal muscle masses. They tend to be at a slightly upper (lateral) level. In difficult cases it may be necessary to use fluoroscopy briefly to identify the appropriate interspace and the mid-line with a marker. A 14-gauge, thin-wall Tuohy needle is then passed parallel to the plane of the floor and directed 10 to 15° cephalad. The needle should be advanced slowly and cautiously because the goal is to enter the subarachnoid space in a single pass. The bevel of the needle is directed horizontally until the dura is penetrated. In many instances, a pop may be felt as the dura is penetrated. The needle is advanced in small increments and the stylet is removed periodically to ascertain whether the subarachnoid space has been entered. This careful maneuver prevents going past the ventral dura and thus hitting the ventral dural venous plexus. Once the arachnoid has been pierced and the stylet has been removed, a gush of spinal fluid escapes because of the size of the needle. In some instances the fluid flows well initially but then stops abruptly because of the tamponading of the tip of the needle by a nerve root. In such instances, gently turning the needle by 30 to 50° will change the direction of the distal aperture of the needle and thus will facilitate better flow. If one is in doubt whether the subarachnoid space has been penetrated properly, a small quantity of a water-soluble contrast agent may be injected through the needle and an anteroposterior roentgenogram taken with a lateral beam which will show the contrast agent in the subarachnoid space. After the placement of the needle into the lumbar subarachnoid space, the bevel of the needle is turned either cephalad or caudad to direct the catheter (Fig. 2C). The stylet is removed and the thin radiopaque lumbar catheter, which has multiple perforations at the end, is inserted through the needle into the lumbar subarachnoid space (Fig. 3A). The insertion is generally easy although the catheter typically hesitates a bit as it maneuvers the curve at the tip of the needle before passing on with relative ease. In exceptional situations, a guidewire can be used to stiffen the catheter and direct it into the lumbar subarach-noid space. In no circumstance should the catheter be withdrawn through the needle because the sharp end of the needle may shear the catheter. If the catheter must be withdrawn for any reason then the needle should be withdrawn along with it. It is not necessary to insert more than 8 or 10 cm of the catheter tube into the lumbar subarachnoid space. In fact, a catheter longer than this may tend to irritate the cauda equina roots because of its entanglement within the roots. If the84CSF is bloody, the lumbar catheter must not be inserted until the fluid is completely clear. During the insertion of the catheter it is best to leave its other end open to monitor free flow which will ensure that it is not being kinked. When the catheter has been passed to the desired length, a lumbar skin incision is made for 1 cm on either side of the needle (Fig. 3B). I prefer to make the incision before the needle is withdrawn because incising the skin after needle withdrawal carries the risk of nicking into the lumbar catheter. The needle is then withdrawn over the catheter; the surgeon should hold the catheter at the skin puncture so it does not get pulled out. A small hemostat protected with rubber sleeves is used to clamp the tip of the catheter. Near the entry site of the lumbar catheter into the spine, the catheter is anchored to the lumbodorsal fascia with a butterfly suture clamp (Fig. 3E). 85 Figure 3. A, insertion of the lumbar catheter through the Tuohy needle. B, a skin incision is made on either side of the Tuohy needle. The presence of the needle prevents the catheter from being nicked by the knifeblade. C, D, the lumbar catheter is brought to a flank incision with a subcutaneous tunneler. E, the lumbar catheter is anchored to the lumbodorsal fascia with a butterfly suture clamp (enlarged view). Flank Dissection A horizontal 5 cm flank incision is made midway between the costal margin and the top of the iliac crest. The 86 incision is deepened through the subcutaneous fatty layer until the fascia covering the external oblique muscle is exposed. Self-retaining retractors are inserted. Using a tissue tunneler, the lumbar catheter is brought into the flank wound from the lumbar area (Fig. 3C and D). The lumbar catheter is again clamped. Minilaparotomy A horizontal incision is made about 2-4 cm above the umbilical level, extending from the midline to the lateral border of the rectus abdominis muscle (Fig. 4A). The skin, subcutaneous tissue, and anterior rectus sheath are incised horizontally, and self-retaining retractors are inserted (Fig. 4B). Subcutaneous bleeders are coagulated. The rectus abdominis muscle is split using a hemostat or any other appropriate blunt instrument (Fig. 4C). The posterior rectus sheath is exposed and it is grasped with hemostats and lifted up. Using a No. 15 blade knife or blunt-tipped scissors, it is incised. I make sure that the peritoneum is also incised. Fatty tissue extrudes out of the opening (Fig. 4D). Make sure that this represents omentum and not preperitoneal fat. If the peritoneal cavity has indeed been entered, one should be able to insert almost three-fourths the length of a blunt Freer elevator (about 5 inches) easily and without any resistance. The distal end of the peritoneal catheter (which has a square tip) is inserted into the peritoneal cavity using a bayonet forceps, and the catheter is directed toward the subhepatic space (Fig. 4E). The peritoneal catheter has two or three slits near the end. These slits are designed to open in case the tip of the catheter gets plugged. These slits do not function as slit valves but merely as additional ports. The catheter then is tunneled through the subcutaneous space and brought into the flank wound (Fig. 5A). Final Shunt Assembly The valve unit should be filled with saline to remove the air pocket from the valve, through a blunt needle attached to the inlet side (clear) tubing. The lumbar tubing is trimmed to the desired length and connected to the inlet side of the valve unit with the stepdown connector. The connection is secured with 3-0 silk ligatures. The clamp on the lumbar catheter is released. If the valve is now held in a horizontal position, the CSF will flow out of the outlet side of the valve. The lumbar catheter is then reclamped. The free end of the peritoneal catheter is brought into the flank wound and excess length is cut off (Fig. 5B). The peritoneal catheter is connected to the outlet side (opaque tubing) of the valve unit using a straight connector (Fig. 5C). For optimal functioning of the valve unit, it should be oriented properly. A properly oriented valve unit will have its long axis parallel to the long axis 87 of the trunk of the patient (Fig. 5D). The arrow on the inlet valve should point toward the patient’s feet. The valve is secured to the fascia overlying the external oblique muscle by passing fine Nurolon sutures through the four holes in the valve housing (Fig. 5D). The shunt assembly is now complete. Lumbar, abdominal, and flank wounds are closed in layers using absorbable sutures. Subcuticular skin sutures are used. 88 Figure 4. incision A, the skin used for the minilaparotomy. B, incision of the anterior rectus sheath. C, longitudinal blunt separation of the rectus abdominis fibers. D, incision of the posterior rectus sheath and the peritoneum; a portion of the omentum extrudes out. E, insertion of the distal catheter into the peritoneal cavity. Figure 5. A, a tunneler is used to bring the peritoneal catheter to the flank incision. B, the peritoneal catheter is brought into the flank wound (note the clear tubing on the inlet side of the valve unit and the opaque tubing on the outlet side). C, the peritoneal catheter is attached to the valve unit. D, the final orientation of the valve unit after the lumbar and peritoneal catheters have been attached to it. The valve unit is being anchored to the fascia over the external oblique muscle through the four holes in the valve unit. POSTOPERATIVE MANAGEMENT The patient is maintained on intravenous fluids for about 24 hours until active bowel sounds are heard and bowel activity is established. The patient is then started on clear liquids, progressing to a regular diet. Adequate narcotic analgesics are administered. To ensure that the patient gets acclimatized to the shunt, the head of the bed is gradually elevated in increments over a period of 24 hours and the patient is generally allowed to sit on the side of the bed by 48 hours. The patient can then get out of89bed in a chair for a few hours at a time and is allowed to ambulate on the third or fourth day. This cautious management facilitates the patient getting used to the new CSF dynamics. Usually the patient is ready to be discharged on the fifth postoperative day. A follow-up CT or MRI study is obtained one month postoperatively which will confirm normalization of ventricular enlargement. Patients with pseudotumor cerebri are monitored serially with visual field testing, visual acuity measurements, and fundus photography. COMPLICATIONS OF SURGERY Like any shunt, the lumbar-peritoneal shunt is susceptible to infections. The incidence of infection is low because no component of the shunt is in the venous system. If shunt blockage is suspected, it has to be confirmed by a radionuclide study. The radionuclide is injected into the lumbar subarachnoid space and the flow of the nuclide through the shunt into the peritoneal cavity is monitored. If the shunt is patent, the radionuclide should escape into the peritoneal cavity within minutes after injection. If it is not functioning, the shunt will need to be replaced. About 1 to 2% of the patients present with manifestations of cauda equina root irritation. In most instances this is transient and resolves with time. If this persists, the lumbar catheter will need to be replaced. Headaches are uncommon but may occur if a proper valve with appropriate pressure has not been chosen. Lack of precipitous drainage of CSF in the upright position, attributable to the unique shunt design, has kept the incidence of subdural hematoma very low. Even if a subdural hematoma occurs, it is seldom of the massive degree that is seen with the single pressure opening device. Migration of the catheter from the spinal canal should not occur if the lumbar catheter has been properly anchored to the lumbar fascia with 90 ii. Optic nerve sheath decompression (ONSD) ONSD has a high success rate in improving or stabilizing visual function in IIH, at least in the short to medium term. It is less effective in dealing with headache, and over time a significant number of patients will require further treatment, whether it be repeat ONSD, medical treatment or other surgical measures, either to control headache or to deal with later visual deterioration.139 The mechanism by which ONSD works has not been clarified, but several theories have been suggested. Keltner suggests that it may provide a filtering effect, with a subsequent decrease in the local CSF pressure, improvement of the peri-papillary circulation, or produce a generalized decrease in ICP.15 According to another hypothesis, the scarring of the arachnoid by the procedure itself may protect the nerve head from elevated CSF pressure.31 Technically, ONSD is performed by uncovering the optic nerve sheath through a lateral orbitotomy or through a medial approach via a trans-conjunctival incision. Multiple linear incisions are made or a window is cut into the anterior dural that covers the optic nerve sheath, creating a CSF drainage outlet.151 There is a moderate complication rate for the procedure although the great majority of complications are either minor or transient or both. The overall complication rate ranges from 4.8% to 45%, Complications includes148: • Ocular motility disorders (e.g. temporary horizontal motility disorder caused by disinsertion of the medial rectus muscle or combined third and sixth nerve palsies). • Chemosis. • Chorio-retinal scar from excessive traction on the globe. • Orbital haemorrhage. • Trauma to the optic nerve. • Micro-hyphaemas. • Orbital apex syndrome. • Optic nerve cyst formation with proptosis, pain and vision loss. • Streptococcal corneal ulcer. • Dacryocystitis. • Deterioration of visual function, transient blindness, choroidal infarction. • Central or branch retinal artery occlusion. 91 In the majority of patients, post-ONSD vision stabilizes or improves but its long-term efficacy remains in question. Also there is evidence that CSF pressure may remain high despite clinical improvement. A reoperation can be performed, a shunting procedure is recommended in these cases.139 iii. Venous sinus endovascular stenting Transverse cerebral venous sinus stenosis is a common finding in patients with IIH. Their origin and functional significance remains controversial. It has been postulated that patients with increased ICP develop the stenosis due to external compression of the venous sinus. Indeed, the stenosis sometimes resolves when ICP is reduced by lumbar puncture or shunting. Modelling studies have suggested that stenting of these stenosis might reduce cerebral venous pressure, leading to increased CSF absorption, reduced ICP, and improved symptoms and signs, even if the stenosis are caused by increased ICP. 152 Supporting this hypothesis are the findings of case studies and series, in which patients have undergone endovascular stenting of this stenosis, with subsequent normalization of ICP and resolution of symptoms and signs.20;24;103 It is highly controversial whether venous sinus narrowing is the cause or the result of elevated intracranial pressure. Based on the frequent findings in MRI venography of narrowed transverse sinuses, endovascular stenting of the venous sinuses has been recently advocated by some authors.20 Higgins et al was the first to report on a 30 year old patient with refractory IIH, papilledema and bilateral transverse sinus stenosis found on an MRV that was successfully treated with dilation of one of the sinuses with a stent, thus reducing the pressure gradient with dramatic symptomatic improvement.21 With the patient under general anaesthesia, a percutaneous venoplasty is performed. A stent is then deployed at the site of the previous stenosis (Fig.34). Manometry is often performed following deployment of the stent, to confirm that any pressure gradient across the stenosis has been alleviated. Long-term antiplatelet treatment is required to prevent in-stent thrombosis. Contraindications of this procedure have not been clearly defined, but might include active infection and use of anticoagulants. Common complications include transient frontal or temporal headache, due to stretching of the meninges covering the transverse sinus. Transient hearing loss has also been reported. There are reports of more serious complications, including in-stent thrombosis, subdural haemorrhage, and death in one patient.20;137 Few patients develop recurrent stenosis proximal to the stent because of the triangular anatomy of 92 the venous sinus which leads to collapse of the segment immediately proximal to the cylindrical stent, with recurrent symptoms and signs of increased ICP.24;103 V, ^>*\ Figure 34: IIH in a 32-year-old, non-obese woman. (Left): MRV showing marked narrowing of the right transverse sinus. (Centre): Retrograde sinography and manometry showing focal obstruction of the right transverse sinus and associated intraluminal pressure gradient. (Right): Repeat retrograde sinography and manometry post-dilatation showing improvement in flow and pressure gradient. All pressures in mmHg.22 Figure 35: A case of a 9-year-old boy with a large dominant right transverse sinus. (a) Lateral DRCV demonstrating the significant right transverse sinus obstruction. There was a gradient of 11 mmHg across the obstruction. (b) Image during stent deployment. (c) Lateral DRCV of right transverse sinus with the stent fully deployed showing abolition 93 of the obstruction.137 94 Although the promising initial results of long term efficiency of the procedure still needs to be proven, further investigation is still warranted to prove the procedure as a useful treatment technique It is still unclear if primary treatment of the observed stenosis benefits patients with IIH. This should be no surprise, as it is not certain whether the stenosis is the cause or the result of IIH.148 iv. Sub-temporal decompression (STD) The first neurosurgical technique to treat IIH patients, by a sub temporal decompression, was performed by Dandy in 1937. Dandy performed a unilateral sub temporal craniectomy with excellent initial results in alleviating headaches and preventing visual loss. The longterm efficacy of the procedure was uncertain, since a high rate of morbidity and complications were reported, including seizures, infections, focal brain damage, cosmetic disfigurement, intracranial hematomas, and further visual deterioration.34 In summary, it does appear that STD still has a place in the management of IIH, albeit a somewhat limited one. Thus, it might be employed in patients who have proceeded to one of the other surgical treatments (optic nerve sheath decompression or CSF shunting) and have continuing problems, either failure to control the disease (ONSD), or recurrent malfunction, or other complications (shunting). If, in such refractory cases, STD is decided upon, it should probably be bilateral and large with a careful technique including splitting of the dural layers to form over-riding flaps, or scoring the dura with multiple lines without penetrating it, to protect the cortical surface.139 Outcomes The natural history of IIH is unknown. In some cases, it is a self-limited condition, while in others ICP may remain elevated for many years even if systemic and visual symptoms resolve. In some patients, the process may last from months to years. Individuals with mild to moderate visual loss tend to recover vision following medical therapy. Papilledema usually resolves after a few weeks or months, but many patients are left with some residual disc elevation, especially nasally. Severe visual impairment may be a serious and permanent complication of IIH. IIH produces significant visual impairment in approximately 25% of patients. The risk of visual loss in the paediatric IIH population is similar to that of adults. Recurrent symptoms have been reported in 8 to 37% of patients, years after being diagnosed.4 Visual deterioration in IIH patients is usually gradual, but in cases of fulminant papilledema, blindness may appear rather quickly. In Corbett et al. follow up study of 5 - 41 95 years after the initial diagnosis of 57 patients, revealed severe visual impairment in 14 patients (24.6%)4 In Kesler et al. experience, recurrence was frequently associated with weight gain. The long term prognosis and visual outcome of 54 patients with IIH was observed over a period of 6.2 years. The results showed that recurrences occurred in almost 40% of the cases. None of these exacerbations occurred during the first 10 months, and none occurred while the patients continued treatment.33 There are several aspects pertaining to outcome which merit separate and particular consideration. These aspects include the outcome for visual function, psychological sequelae and persistence elevation of CSF pressure.153 ♦ Outcome for visual function A significant proportion of IIH patients will be left with permanent impairment of vision involving visual acuity, visual field or both. While there is quite considerable variation in the reported incidence of such impairment, it is probably of the order of 10-20% with current methods of management and evaluation. In general, the likelihood of such loss is related to the chronicity and severity of the intracranial hypertension, this causing prolonged disturbance of axoplasmic flow in the optic nerves with secondary vascular changes which may themselves be irreversible, or which may lead to irreversible changes.153 ♦ Psychological and psychiatric sequelae There is the largely unexamined issue of whether there are significant psychological or psychiatric problems associated with IIH, particularly if the condition itself is of long duration, but also if, as considered above, there is prolonged elevation of CSF pressure despite amelioration of symptoms and signs. 96 There are several reports of a coincidence of IIH and depression. The only formal examination of a possible association is the study by Kleinschmidt et al. who compared three groups of patients: 1) IIH patients, 2) age and weight-matched controls, 3) age-matched controls of normal weight. They found higher levels of depression and anxiety, and a greater number of adverse health problems in the IIH group compared to both control groups whereas there were no differences with respect to non-health-related psychosocial problems.154 ♦Persistent elevation of CSF pressure It was evident from the findings using continuous ICP monitoring as part of the follow-up after clinically successful treatment of IIH with steroids that despite the undoubted resolution of all clinical symptoms and signs, there could be a persistent and not insubstantial increase in CSF pressure. Using single manometric readings of CSF pressure on lumbar puncture, a similar claim could be made for apparently successful treatment by subtemporal decompression. More recently, similar findings were obtained in a small group of patients treated by optic nerve sheath decompression and direct treatment of cranial venous outflow obstruction.153 11. 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