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“ЗАТВЕРДЖЕНО” на методичній нараді кафедри нервових хвороб, психіатрії та медичної психології “______” _______________ 2008 р. Протокол № _____ Зав. кафедри нервових хвороб, психіатрії та медичної психології професор В.М. Пашковський METHODOLOGICAL INSTRUCTION № 11 THEME: AUTONOMIC NERVOUS SYSTEM SYNDROMES OF LESION. METHODS OF EXAMINATION Modul 1. General neurology Сontents modul 2. Pathology of the cranial nerves. The disorders of the autonomic nervous system and brain cortex functions. Meningeal syndrome. The additional methods of examination in neurology. Subject: Nervous deseases Year 4 Medical faculty Hours 2 Author of methodological instructions MD Filipets O.O. Chernivtsy 2008 1. Scientific and methodological substantiation of the theme. The autonomic nervous system is a purely efferent system of nerve fibers with ganglia and plexuses outside the central nervous system innervating the blood vessels, heart, viscera, glands, and smooth muscles throughout the body. The vegetative disturbance have own specific clinical signs. 2. Aim: students should be able to determine independently signs of lesion Autonomic nervous system, to localize the pathological process (focus) on different topical levels. Students should be able to formulate and to explain the topical diagnosis. Students must know: 1. Anatomical structures and function of the Autonomic nervous system. 2. Specific methods of examination of Autonomic nervous system. 3. The signs of lesion of sympathetic part of vegetative nervous system. 4. The signs of lesion of parasympathetic part of vegetative nervous system. 5. Hypothalamic syndromes. 6. Lesion of limbic-reticular complex. 7. The paroxysmal and permanent disturbances of vegetative function. Students should be able to: 1. Examine patient status: a. activity of inner organs (attacks of tachy- and bradycardia, breath, dyspeptic disturbance after meals, abdominal spastic pain, diarrhea, frequent and abundant urination) b. activity of cardiovascular system (attacks of a skin pallor and hyperemia, high and low of blood pressure) c. activity of the sweating, sebaceous glands and lacrimal organs (salivation, hyperhidrosis, dry skin, eyewatering) etc d. activity of pelvic (urogenital) organs (ischuria/retention of urine/, incontinence of urine and feces) e. trophic disturbance (hyperkeratosis, skin lesion, peeling of the skin, fissures of skin, pustules, skin edema, hyperpigmentation, alopecia, hemiatrophia) f. disturbance of the height and substances exchange (low and high height, increasing of weight, cachexia, acromegalia) g. disturbance of sleep, thermoregulation, memory, emotions and tendencies 2. Localize the pathological processes on different levels of somatic nervous system. 3. To put topical diagnosis and to explain it. 1. 2. 3. 4. 5. Student should gain practical skills: To examine pupillary reaction, eye-heart reflex, solar reflex, vascular responses of the skin (local and reflex). To find the difference in blood pressure levels on hands and legs. To diagnose the pathological processes on different levels of somatic nervous system. To examine temperature and activity of sweating (apirine test). To provide pharmacological tests (atropine, adrenaline, pylocarpine). 4. Integration (basic level). Subjects Anatomy Gained skills Knowledge of anatomy of sympathetic and parasympathetic divisions of autonomic nervous system Histology Hystological structure of the sympathetic and parasympathetic divisions of autonomic nervous system Physiology Knowledge of function of vegetative reflex arch . Subject Unlike the somatic nervous system, which senses and responds to changes in the external world, the visceral nervous system senses and responds to changes within the environment inside the body. The primary function of the visceral nervous system is to maintain the internal environment within physiological limits (homeostasis). Most visceral regulation is achieved via reflexes at subconscious levels. Components of the visceral nervous system exist at all levels of the neuraxis (forebrain, midbrain, hindbrain, spinal cord, and periphery) and they regulate the function of smooth muscle, cardiac muscle, and glands. To control these effectors, the visceral system uses both neural and humoral (hormones released into the blood) mechanisms. In addition to neurohumoral differences with the somatic nervous system, the visceral nervous system has two other unique characteristics. First, the effector mechanisms are still capable of functioning in the absence of neural control. For example, cardiac muscle continues to contract rhythmically in the absence of neural innervations. Second, the peripheral level of the visceral nervous system contains ganglia that play an important part in the reflex control of effector function. Visceral ganglia are organized into two systems. The paravertebral ganglia form a chain located immediately adjacent to the vertebral column that extends the entire length of the spinal cord and functions in the sympathetic division of the visceral efferent system. The parasympathetic division of the visceral efferent system contains peripheral ganglia that are located in or around the effector mechanism that they innervate. Visceral Afferent System The two primary types of visceral receptors, mechanoreceptors and chemoreceptors, are distributed throughout the body. Mechanoreceptors sense pressure, stretch, or tension. Slow-adapting mechanoreceptors sense fullness in the bowel, bladder, and stomach. Fast-adapting mechanoreceptors sense the movement in the lungs and arteries. The second receptor type, chemoreceptors, exist only in the visceral nervous system. Chemoreceptors sense taste and smell as well as the concentration of hydrogen ions (pH) in the stomach and partial pressure of oxygen and carbon dioxide in the blood. Chemoreceptors located in the hypothalamus and reticular formation respond to the levels of blood sugar and electrolytes. These receptors help the hypothalamus to regulate hunger and thirst. Visceral afferent fibers are small-diameter, myelinated and unmyelinated axons that exhibit slow conduction velocity. Some first-order visceral afferent fibers project only as far as the peripheral ganglia while others project into the spinal cord and brain stem, and ascend to higher levels of the brain. Two pathways exist for peripheral afferent fibers. They either join with peripheral and spinal nerves to project directly into the spinal cord or they follow blood vessels centrally until reaching a ganglion. The fibers that project to ganglia may either synapse and terminate, pass through the ganglion giving off a collateral synapse, or pass directly through the ganglion and enter the central nervous system (CNS). Visceral afferent fibers that enter the central nervous system have their cell bodies located in the dorsal root ganglia or the sensory portion of a cranial nerve nucleus. To enter the spinal cord, visceral afferent fibers join spinal nerves by projecting through the ganglion and white ramus communicans (communicating branches that are white because they are myelinated) and enter the spinal cord along with the other fibers of the dorsal root. In the brain stem, fibers project directly to cranial nerve nuclei. The visceral afferent fibers that enter the central nervous system establish multiple synaptic connections at the level of entry. They synapse with both visceral and somatic efferent neurons. Synaptic connections with visceral neurons form the anatomical basis for central visceral reflexes. Synaptic connections with somatic neurons form the basis for associated somatic and visceral behaviors such as the postural collapse that often accompanies severe visceral pain. The convergence of visceral and somatic fibers onto a postsynaptic neuronforms the anatomical basis of referred pain. Referred pain originates from a deep visceral organ (heart, appendix, etc.) but is "referred" to more superficial areas of the body with the same segmental representation in the spinal cord. Visceral afferent information ascends in the spinal cord and brain stem via the lateral spino-thalamic tract and dorsal columns to the reticular formation and then up to the hypothalamus, thalamus, and cerebral cortex. In spite of cortical projections, the primary destination of visceral afferent activity is the hypothalamus. The hypothalamus is the integrator of visceral information that it receives from the periphery, spinal cord, reticular formation, thalamus, and rhinencephalon. The visceral nervous system contains large numbers of afferent fibers (the vagus nerve contains approximately 80 percent afferent fibers), but conscious perception of visceral sensations is limited to the stomach, bowel, and bladder under normal circumstances. Most visceral function is controlled by subcortical reflexes, which makes diagnosis and localization of visceral dysfunction extremely difficult. Visceral Efferent System The visceral nervous system exerts control over smooth muscle, cardiac muscle, and glands via three pathways: sympathetic, parasympathetic, and humoral. Together, the sympathetic and parasympathetic pathways comprise the autonomic nervous system. Both these divisions are two-neuron systems and consist entirely of efferent fibers. The Sympathetic Division. The sympathetic division has components in the hypothalamus, reticular formation, spinal cord, and periphery. It assumes responsibility for the control of activating types of behavior, such as dilation of the pupil, increased heart rate and respiratory rate, and the shunting of blood to the peripheral musculature, all of which prepare the body to respond to stress. Descending fibers from the hypothalamus and reticular formation are located in the lateral brain stem and spinal cord. The cell bodies of preganglionic sympathetic neurons are located in the lateral horn of the gray matter in the first thoracic through third lumbar segments of the spinal cord (T1-L3). Anatomically, the sympathetic division is referred to as the thoracolumbar division of the autonomic nervous system. Short preganglionic fibers exit the spinal cord via the ventral root and project to the paravertebral ganglia via the white rami communicantes. The white ramus is so colored because preganglionic sympathetic fibers are myelinated. Once inside the paravertebral ganglion chain (which extends from the first cervical vertebra to the coccyx), preganglionic fibers project in one of three ways. They may synapse immediately with postganglionic fibers, ascend or descend within the ganglion chain before synapsing with postganglionic fibers, or pass through the paravertebral ganglia without synapsing. These direct projecting fibers are myelinated and form the three splanchnic nerves (superior, inferior, and lowest) that synapse in the prevertebral ganglia (ciliac, superior mesencephalic, and inferior mesencephalic). Before synapsing, single preganglionic fibers diverge extensively to form synaptic connection with as many as 10 postganglionic neurons, which distribute sympathetic stimulation widely throughout the body. Long unmyelinated postganglionic fibers exit the ganglia via the gray rami communicantes and provide the sympathetic innervation to effector mechanisms. Postganglionic fibers join with peripheral nerves and project directly to effectors. Preganglionic sympathetic fibers produce shortlived facilitation of postganglionic neurons by using acetylcholine neurotransmitter substance. Postganglionic fibers produce long-lived, generalized, and specific activation of effector mechanisms by using norepinephrine neurotransmitter substance. Based on the transmitter substance used, most preganglionic fibers are classified as cholinergic and most postganglionic fibers as adrenergic (sweat glands and blood vessels in skeletal muscle are exceptions). The Parasympathetic Division. The parasympathetic division of the autonomic nervous system arises from the brain stem and sacral segments of the neuraxis and is therefore referred to as the craniosacral division. This division assumes responsibility for regulating restorative types of behavior, including eating, sleeping, and digestion. Stimulation of parasympathetic fibers increases digestion and the absorption of nutrients, drainage of the bowel and bladder, decrease of heart rate and respiratory rate, and shunting of blood to the digestive system from the musculoskeletal system. Parasympathetic ganglia are located distal to the central nervous system in or near the effector mechanism. Thus, preganglionic fibers are long and postganglionic fibers are short. Both preganglionic and postganglionic fibers of the parasympathetic division produce specific, short-lived effects on postsynaptic membranes by using acetylcholine neurotransmitter substance. The entire parasympathetic division is classified as a cholinergic system. Long preganglionic fibers from cranial segments exit the central nervous system with efferent fibers from the oculomotor (III), facial (VII), glossopharyn-geal (IX), and vagus (X) cranial nerves. Oculomotor, facial, and glossopharyngeal nerves innervate structures in the head and throat. Parasympathetic ganglia in the head region are discrete constellations of neurons, smaller than the head of a pin. The ciliary ganglion is located just behind the eyeball and helps regulate the shape of the lens and diameter of both the lens and the pupil. The sphenopalatine ganglion is found in the lateral wall of the nasal cavity near the nasopharynx and helps to regulate the glands of the eye and nasal and oral cavities. The submandibular ganglion is located inside the jaw and helps to regulate parotid (salivary) glands. The optic ganglion is found just inside the mandible, beneath the temporal bone, and helps regulate sublingual and submaxillary (salivary) glands. The vagus nerve contains approximately 75 percent of all parasympathetic outflow from the cranial region. The vagus nerve provides the parasympathetic innervations to the organs of the thorax and abdomen. An increase in the parasympathetic activation from the sacral region stimulates digestion and excretion. In the second, third, and fourth sacral regions (S2, S3, S4), the cell bodies of preganglionic fibers are located in the lateral region of the ventral horn. The sacral outflow provides the parasympathetic innervation to the urinary system, lower colon, anal sphincter, and reproductive system. Preganglionic fibers exit the spinal cord via the ventral roots and project in the pelvic nerve to synapse with postganglionic parasympathetic neurons in the pelvic ganglion plexus. Postganglionic parasympathetic neurons innervate the descending colon, bladder, and external genitalia. Table 1 compares the sympathetic and parasympathetic divisions. Table 1. Comparison of Sympathetic and Parasympathetic Divisions Component Sympathetic Parasympathetic CNS segments of origin Thoracic-lumbar region of the spinal cord Cranial-sacral regions of the spinal cord Location of ganglia Paravertebral ganglion chain On or near effector organ Preganglionic neuron Short, myelinated Long, myelinated Preganglionic neurotransmitter substance Postganglionic neuron Acetylcholine Long, unmyelinated Postganglionic neurotransmitter Norepinephrine substance Acetylcholine Short, unmyelinated Acetylcholine Divergence ratio 1:10 1:3 Outflow specificity Can be widespread Can be specific Specific Behavior produced with stimulation "Fight or flight" Sedentary activities Voiding Effect on energy stores Energy mobilization Energy utilization Inhibition of digestion Energy conservation Energy restoration Stimulation of digestion The Enteric Division The enteric division is concerned with control of the gastrointestinal tract, pancreas, and gallbladder. Because these structures contain sensory receptors, afferent neurons, peripheral ganglia, and efferent neurons, their control is sometimes referred to as the enteric nervous system. Although the enteric nervous system is capable of functioning independently, its activity is normally regulated by CNS reflexes. Because of its role in controlling digestion, the enteric division plays a major part in homeostasis. The neurons of the enteric division are arranged in complex interconnecting plexuses of ganglia and nerve fibers located between the layers of muscle and endothelium. Extrinsic innervation of the enteric division is supplied by both the sympathetic and parasympathetic systems. Sympathetic innervation consists primarily of postganglionic fibers from the cervical paravertebral chain. These fibers project to ganglia in the wall of the stomach, small intestine, and colon. Parasympathetic preganglionic fibers project directly to enteric ganglia in the stomach, colon, and rectum through the vagus and pelvic splanchnic nerves. Autonomic innervation, both sympathetic and parasympathetic, provides a second level of control of digestion that is capable of overriding intrinsic enteric control in situations of emergency and stress. Central Visceral Control. The central control of the visceral nervous system includes three primary areas: the cerebral cortex, hypothalamus, and reticular formation. In the visceral nervous system, cortical centers play a minor role in central control. The two cortical centers, the ventrobasal frontal lobe and the rhinencephalic cortex (medial surface of frontal and temporal lobes), function mainly to integrate somatic and visceral information. Efferent pathways from these areas project directly to the hypothalamus, mamillary bodies, and brain stem reticular formation. There are no direct projections into the spinal cord. Cortical centers coordinate emotional and visceral reactions such as blushing, which is associated with embarrassing situations. The visceral cortex is part of the larger limbic system, which regulates most human emotions and their associated visceral reactions. Limbic and visceral structures are commonly involved in emotional disorders. The hypothalamus is the major region of central visceral control. All visceral sensory information is projected to the hypothalamus and the hypothalamus has efferent projections to other visceral and limbic areas of the cortex, reticular formation, and spinal cord. Both afferent and efferent visceral pathways are diffusely organized. The hypothalamus has primary responsibility for regulating restorative and preparatory behavior as well as homeostasis. The anterior hypothalamus controls the posterior hypophysis and parasympathetic system, which regulate restorative types of behavior. The posterior hypothalamus controls the adenohypophysis and sympathetic system, which regulate preparatory types of behavior. The medioventral hypothalamus uses the neurohypophysis to regulate homeostasis. The reticular formation, the remaining area of importance in the central control of the visceral system, is among the oldest structures in the mammalian brain. It extends from the midbrain through the brain stem and consists of numerous centers that control specific, visceral, life-support functions such as heart and respiratory rates. Reticular centers are not discrete nuclei but, rather, clusters of cells that regulate specific visceral function. Opposing Mechanisms or Functional Synergy. Most visceral effector organs receive innervation from both postganglionic sympathetic and parasympathetic fibers. Sympathetic neurotransmitter substances (epi-nephrine and norepinephrine) tend to increase effector function while parasympathetic neurotransmitter substance (acetylcholine) tends to decrease effector function. Both types of efferent fibers are tonically active. Thus, the level of activity of visceral effector organs is determined by the dynamic equilibrium between sympathetic and parasympathetic stimulation. For example, norepinephrine released from postganglionic sympathetic fibers acts on cardiac muscle to increase heart rate and contractility, whereas activation of postganglionic parasympathetic fibers in the vagus nerve causes the release of acetylcholine, which profoundly decreases heart rate and contractility, thereby decreasing cardiac output. Thus, adaptive responses are executed or homeostasis is maintained by varying autonomic drive (sympathetic or parasympathetic) of visceral organs in proportion to external challenges to the system. Limbic system. The components of the limbic system are restricted to the forebrain, and midbrain. The limbic system controls emotions (drive, motivations) and affect. Because of the prominent visceral component in each of this types of behavior, the function of the limbic system is inextricably linked with that of the visceral nervous system, and is therefore sometimes referred to as the “visceral brain”.Limbic structures include the hippocampus, fornix, mamillary bodies, anterior nucleus of thalamus, and cingulated gyrus, as well as regions of temporal, parietal, and frontal lobes. Clinical Aspects. High blood pressure, or hypertension, is the most common health problem associated with the cardiovascular system. Hypertension leads to cerebrovascular accidents, heart attacks, and kidney failure, which kill tens of millions of people every year. Hypertension has many causes; however, increased sympathetic drive is one important factor in the development and maintenance of high blood pressure. Sympathetic stimulation increases both cardiac output and peripheral vascular resistance, the two leading determinants of blood pressure. Antihypertensive drugs lower blood pressure by decreasing sympathetic drive. Beta-adrenergic blocking agents reduce the sympathetic drive to the heart, thereby reducing cardiac output. Alpha-adrenergic blocking agents reduce peripheral vascular resistance by interfering with the vasoconstriction produced by the norepinephrine released from sympathetic fibers. Autonomic dysreflexia or sympathetic hyperreflexia is a specific type of hypertension found in individuals with spinal cord lesions above T7. An abnormal sympathetic response to bladder or bowel distention or painful stimuli in the viscera produces dangerous increases in blood pressure, headache, perspiration, and chills. This response is not self-limiting and is therefore potentially life threatening. Postural hypotension is a less dangerous though more common blood pressure abnormality. Postural or orthostatic hypotension (low blood pressure) produces lightheadedness or fainting after rising from a recumbent or sitting position. The condition results from a failure of the visceral nervous system in sensing and responding adaptively to the change in blood pressure. As the person stands up, gravity pulls the blood into the lower extremities. Unless the tension in the vasculature of the lower extremities is increased proportionately, blood will pool in the legs, perfusion of the brain will drop, and consciousness will be lost. The baroreceptor reflex normally senses and responds automatically to changes in aortic blood pressure in order to maintain blood flow to the brain. The exact cause of postural hypotension, pressure receptors, afferent transmission, CNS integration, peripheral sympathetic or parasympathetic efferents, or effector response to stimulation remains unknown. Diabetes mellitus produces widespread problems throughout the body, including peripheral neuropathy involving both somatic and visceral neurons. Smalldiameter neurons, both myelinated and unmyelinated, are the most vulnerable. The clinical symptoms of autonomic diabetic neuropathy often include cardiovascular control and gastrointestinal motility. The inability to produce and utilize adequate amounts of insulin causes metabolic breakdown and loss of function in the neurons that control these functions. The papillary reaction. Normally the pupils are round and equal in diameter. Normal pupils are small in sleep and dilate with arousal. Difference in size (anisocoria), if small, may not represent disease and can be evaluated accurately only with reference to other findings, such as ptosis. The large pupil may react poorly to light as a result of a partial third-nerve paralysis, or the smaller pupil may be part of Horner’s syndrome. Horner’s syndrome, when complete, is characterized by: ptosis of the upper lid miosis loss of sweating on the same side of the face papillary reaction to light is normal, but the pupil does not dilate to psychosensory stimuli such as a loud noise. The Argyll Robertson pupils of tabetic neurosyphilis are small (miotic), irregular, an often unequal in size. They react little or not at all to light but constrict promptly when the eyes converge on a near object. A similar dissociation between the light reaction and the near response may be seen in patient with diabetes, encephalitis, and midbrain neoplasm. The disturbance of vegetative function The paroxysmal signs The disturbance of vegetative functions : 1.The paroxysmal signs Sympathy-adrenal attacks: Vagoinsular attacks: a) skin pail a) hyperemia b) xerostomia b) hyperhidrosis c) dryness of hair and skin c) oily skin and hair d) tachycardia d) bradycardia e) high blood pressure e) low blood pressure f) midriasis and widing of Eye-slit f) miosis g) exophthalmia g) angina pectoris h) tremor h) salivation i) gooseflesh i) breathlessness j)abdominal spastic pain k) diarrhea l)frequent and abundant urination 2.The lesion (permanent) signs: a) periarthritis a) incontinence of urine and feces b) epicondilitis b) ischuria/retention of urine c) miositis c) eye accommodation paralysis d) hyperkeratosis d) midriasis e) fissures of skin e) dyspnea f) arthropatias f) apnea g) tropic ulcer g) cardiac arrhythmia h) alopecia h) asystolia i) hyperpigmentation i) collapse j) Horner’s sign (ptosis, miosis, enophthalmia) Self assessment: Tests for self-assessment: 1. Clinical features of sympathy-adrenal attack. 2. Clinical features of vago-insular attack. 3. Enumerate hypothalamic syndromes. 4. Name the symptoms of lesion of limbic-reticular complex. 5. Describe vegetative-trophic disorders in case of lateral horns of spinal cord lesion. 6. Describe the irritation symptoms of sympathetic nerve of vertebral artery. 7. Enumerate hypothalamic realizing-factors. 8. Enumerate hypothalamic inhibits factors. Tests 1. What makes a part of suprasegmental division of autonomic nervous system a) truncus simpaticus; b) Nucleus ruber; c) hypothalamus; d) septum pellucidum; e) substantia nigra. 2. a) b) c) d) e) Sympathetic fibers from the cerebrospinal center innervate: M. ciliaris; M. Sphincter pupillae; M. Dilatator pupillae; M. Rectus medialis; M. Obliquus superior. 3. a) b) c) d) e) In what time after skin irritation red vessel reaction appears 1-5 seconds; 5-11 seconds; 20-30 seconds; 25-35 seconds; 30-40 seconds. Real-life situations: 1. Patient has prosoplegia, xerophtalmia, ageysia of anterior 2/3 of tongue. What vegetative structures are damaged? 2. Patient with spastic paraplegia of lower extremities has centrally uninhibited bladder. What part of nervous system is damaged References: 1. Basic Neurology. Second Edition. John Gilroy, M.D. Pergamon press. McGraw Hill international editions, medical series. – 1990. 2. Clinical examinations in neurology /Mayo clinic and Mayo foundation. – 4th edition. –W.B.Saunders Company, Philadelphia, London, Toronto. – 1976. 3. McKeough, D.Michael. The coloring review of neuroscience /D.Michael McKeough/ - 2nd ed. – 1995. 4. Neurology for the house officer. – 3th edition. – howard L.Weiner, MD and Lawrence P. Levitt, MD, - Williams&Wilkins. – Baltimore. – London. – 1980. 5. Neurology in lectures. Shkrobot S.I., Hara I.I. Ternopil. – 2008. 6. Van Allen’s Pictorial Manual of Neurologic Tests. – Robert L. Rodnitzky. 3th edition. – Year Book Medical Publishers, inc.Chicago London Boca Raton. - 1981.