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1 MENINGITIS Robin Cooke 4 Aug 2010 Meningitis is an inflammation of the membranes that cover the Nervous System. It can occur at all ages but it is more common in children. The presenting symptoms are fever, headache, drowsiness and neck stiffness. Convulsions may occur. Untreated, the patient becomes unconscious and the mortality is high. Antibiotic treatment is highly effective in treating most cases of meningitis. The inflammation causes raised intracranial pressure. This can be seen in infants as a tense or bulging anterior fontanelle. Specifically the acute inflammation of the meninges causes neck stiffness. In advanced cases of meningitis, the irritation of the meninges may cause severe spasm of back muscles (opisthotonos.) The diagnosis of meningitis is confirmed by lumbar puncture. The patient lies on his/her side. Children need to be restrained. After skin preparation, local anaesthetic is injected and the needle is inserted into the subarachnoid space. The stillette is removed and CSF drains from the needle. Note is it under increased pressure is it a clear colour turbid or frankly purulent. Normal CSF is a clear fluid. In meningitis it is turbid. If the lumbar puncture is traumatic, it is blood stained. Tests performed on CSF and results in meningitis Measure pressure (increased) Observe turbidity (colour) [cloudy] Protein usually increased Sugar usually decreased A cell count In bacterial meningitis:an increased cell count, mostly neutrophils. In tuberculous, cryptococcal and viral meningitis: There is an increased cell count, mostly lymphocytes. (While these are the usual results, opposite results may be encountered.) 2 An increased cell count (moderately elevated) An increased cell count (very high) The pathology of meningitis Spinal cord with the dura opened to show the leptomeninges that are filled with pus. The brain from the same patient shows the white pus in the subarachnoid space over the surface of the brain. Pus in the interpeduncular cistern can be seen on the basal surface of the brain. Thick pus along the base of the brain may obstruct the flow of CSF. Microscopic examination shows the purulent infiltration in the subarachnoid space over the surface of the brain. Almost all the cells are neutrophils. Commonest organisms Haemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae Gram stain showing the pleomorphic (that is, some organisms are longer than others) gram negative bacilli of H. influenzae. Gram stain showing the gram negative intracellular diplococci of N. meningitidis. Colonies of N. meningitidis growing on a chocolate agar plate. Gram stain showing the diplococci of S. pneumoniae. Note the unstained halo around each pair of cocci. This is the capsule from which pneumococcal vaccine is made. This vaccine has been shown to reduce the incidence of childhood deaths from pneumococcal pneumonia. A blood agar culture plate showing Optochin inhibition typical of S. pneumoniae. An Optochin disc is placed on the agar plate that has been inoculated with the test organism before the plate is incubated. Less common organisms Staphylococcus aureus Cryptococcus neoformans Mycobacterium tuberculosis Free living amoebae (Naegleria) This CSF is blood stained and purulent. Gram stain shows the clumped gram positive cocci of S. aureus. This CSF came from a 40 year old diabetic man. It was so purulent and viscous that it would barely pass through the needle. In spite of the seriousness of the infection, the patient recovered. Gram stain showing gram negative bacilli consistent with coliforms. E. coli was cultured. In this CSF count, there is an increase in mononuclear cells. 3 Some of these cells are lymphocytes and some are not. They are somewhat smaller. An India Ink stain has been performed on the CSF. One drop of CSF was mixed with a drop of India Ink. This accentuated the thick capsule of the organism Cryptococcus neoformans. The budding yeasts can also be seen in the Gram stain which is a routine test on purulent CSF. Subarachnoid space in a cryptococcal meningitis. It shows the characteristic inflammatory reaction elicited by this organism. There is a minimal amount of cellular reaction with large amounts of mucoid material. Within this, one sees the round yeasts surrounded by an unstained halo which represents the capsule of the yeast. A brain scan of an adult patient with cryptococcal meningitis It shows dilated ventricles (A) and two radio opaque areas (B) that represent cryptococcomas (or by the older name for the organism – torulomas) – inflammatory masses that resemble neoplasms. The brain at post mortem confirms the presence of the two cryptococcomas. The brain from a male aged 50 years who died from cryptococcal meningitis. A cryptococcoma in the thalamic region shows the typical multiloculated mucoid appearance of this condition. ZN stain on the CSF of a patient with tuberculous meningitis showing the presence of acid fast bacilli. Microscopic sections from the brain of a male 6 years who died from amoebic meningitis. The small amoebae of Naegleria fowleri can be seen in the perivascular space. There is also a perivascular infiltration of lymphocytes giving the appearance of an encephalitic reaction. Organisms found particularly in neonates: Coliform organisms Listeria monocytogenes Group B Streptococci Brains from neonates who died from meningitis. Both infections were caused by E. coli. Note the very thick pus in the subarachnoid space. This is a gross feature of fatal neonatal meningitis. Complications of meningitis Waterhouse-Friderichsen Syndrome Septicaemia Cortical infarction Obstructive hydrocephalus Cerebral Abscess 4 Subdural haematoma Waterhouse-Friderichsen Syndrome A female 6 months of age was well in the morning, became febrile at mid-day, developed a red, haemorrhagic rash soon afterwards, and died in the late afternoon. This sequence of events can occur at any age, but it is most common in children. It most often occurs as a complication of N. meningitidis infection but other bacteria may cause the syndrome. This post mortem specimen shows bilateral adrenal haemorrhage, a common complication of this syndrome. The haemorrhage causes adrenal failure which was the mechanism of death. With better treatment of adrenal failure the mortality from this condition has gone down significantly. Septicaemia This patient developed a metastatic abscess in the head of his right femur which resulted in shortening of that leg. Cortical infarction Neonatal meningitis complicated by a cortical infarction. (Note in passing that neonatal brains do not have well demarcated grey matter.) Paediatricians carefully measure the head circumference in children with meningitis to check for this complication. Obstructive hydrocephalus A normal cerebellum showing transparent meninges covering the outlets of the fourth ventricle into the cisterna magna. Obliteration of the cisterna magna by the purulent exudate of acute neonatal meningitis in a female aged 3 months. Dilatation of the fourth ventricle. Dilatation of the cerebral aqueduct. Dilatation of the third and both lateral ventricles. Imaging results from this child A plain X-ray of the skull showed raised intracranial pressure causing widening ‘springing’ of the suture lines of the skull. An air encephalogram showed the obstruction to be in the region of the cerebral aqueduct. (Note this investigation has been superseded by MRIs.) Microscopic examination of the aqueduct after death confirmed the site of the inflammatory obstruction. Cerebral abscess Cerebral abscess in the right temporal lobe of the brain of a male aged 9 years. 5 Subdural haematoma A 9 year old male had had many aspirations of a subdural haematoma. At the time of his death there was a chronic haematoma with multiple layers of fibrous tissue.