Meningeal syndrome/Meningismus



Subarachnoidal hemorrhage (SAH):

A large majority of SAH is caused by ruptured intracranial aneurysm (Berry aneurysm = saccular aneurysm). The prevalence of intracranial saccular aneurysms is around 2%. The mean age of rupture is around 50 years of age. About 85% of aneurysms are located in the anterior circulation. Risk factors for rupture include history of prior SAH, smoking, AHT, alcohol abuse, cocaine use, obesity, pregnancy and positive family history. Besides a positive family history which increases the chances 4x, hereditary diseases are associated with increased risk of aneurysms (e.g. polycystic kidney disease, Ehlers-Danlos syndrome type IV, NF-1, and Marfan syndrome). Most commonly rupture occurs in the morning and the evening. Headache (acute, explosive, severe and continuous) is the most typical manifestation associated with nausea, vomiting, meningismus, focal neurological findings and loss of consciousness. Neck rigidity occurs in 75% of cases during the first 24 hours. About 50% of patients may have a presentation mimicking meningitis. A sentinel headache (or warning leak) occurs in 50% of patients before a major rupture of a saccular aneurysm. These headaches present in the same way as the SAH itself. Accurate diagnosis of a sentinel headache can be lifesaving since the mortality of SAH is between 50 - 70%. Fever in SAH is associated with vasospasm (and subsequently stroke, which appears between 3 to 12 days after rupture) and poor outcome independently of hemorrhage severity or presence of infection. Transcranial doppler is preferred above angiography to verify the diagnosis of vasospasm.  Hydrocephalus (e.g. increasing confusion or stupor) may develop acutely or may appear after 2 - 4 weeks.


SAH can result in RBCs in the CSF, xanthochromia or both, depending on the timing of the LP relative to the SAH. A rule which is applicable here is the “rules of halves”: half an hour after an SAH, RBCs appear in the CSF; at half a day, xanthochromia appears; at half a week, the RBCs disappear; and at half a month the xanthochromia resolves. Immediate centrifugation of the supernatant is the most reliable way to differentiate a “traumatic tap” from preexisting SAH. In the latter, xanthochromia will be observed by spectrophotometry in the supernatant. Hyperbilirubinemia may also result in xanthochromia. (Acute onset headache - SAH) The first day of SAH, CT scan is able to detect 95% of cases and precludes the need for LP. This figure gradually reduces to 30% after 2 weeks. MRI (FLAIR) is more sensitive than CT scan. LP should be done on all patients suspected of SAH but with normal CT scans or MRI. MRI gradient echo has a sensitivity of 94% in early stage and 100% sensitivity after 4 days. In contrast to bloody tap, the CSF is under increased pressure (up to 500 mmH2O) at least during the first day after the event. The blood WBC/RBC ratio (1:1000) is a good indicator of SAH, but leucocytosis up to 18,000 cells/mm3 (with normal ESR) may be found in the early days. Similarly, CSF RBC hemolysis may alter the WBC/RBC ratio, resulting in higher relative WBC count. It is worth mentioning that this procedure may precipitate rebleeding from a ruptured aneurysm. Arteriogram (four vessel angiography) does not reveal the cause of bleeding in 15% of cases (probably due to vasospasm and may require second angiogram in several weeks). In cases with negative angiogram the risk of rebleeding is 4%. Survival rate after 20 years is 69%. To reduce the risk of rebleeding with its high mortality and prevent stroke from vasospasm, Hunt & Hess grade I and II patients should have surgery done within 36 hours after the ictus. Those cases can be related to occult aneurysm, dural or spinal AVM, mycotic aneurysm, sickle cell disease, coagulation disorders, drug abuse (ecstasy, cocaine abuse), intracranial or cervical tumors and HSE. Systemic complications related to SAH, are myocardial ischemia, hyponatremia (SIADH) and leucocytosis (with normal ESR). The patient's state of consciousness (Hunt & Hess grade) at the time of angiography appears to be the best indicator of prognosis. Health outcomes for survivors 1 year after the onset of SAH: 56% are alive after 1 year; 46% recover incompletely (memory impairment (50%)), mood problems (39%), speech problems (14%) and self care (10%). Seizures at onset (observed in 4-16% of patients) are a predictor of poor outcome. Perimesencephalic hemorrhage has a favorable outcome. Headache is mild and vasospasm rarely develops. The aneurysm at the top of the basilar artery is seldom visualized and may be of venous origin.


Acute bacterial meningitis: In adults with hematogenous infection usually a single type of organism is found. The most common pathogenic organisms are S. Pneumoniae, N. meningitides and H. influenza (particularly in chronic lung disease patients, splenectomized patients and immunocompromized patients), accounting for 75% of all sporadic infections. Listeria monocytogenes (chronic illness, malignancy, organ transplantation, AIDS or immunosuppressive therapy), staphylococcus (brain abscess, trauma and neurosurgery), S. agalactiae (elderly with underlying disease), Klebsiella, Proteus and Pseudomonas (LP, spinal anesthesia and shunting for hydrocephalus) are accounting for the remainder. When infection disseminates from the lungs, heart or extends from ears or sinuses more than one type of bacterial flora may be observed. Fever, severe headache, neck stiffness (predominantly on forward flexion unlike the multidirectional rigidity in extrapyramidal disorders or paratonia), seizures (17% in community-acquired forms) and alteration of consciousness are early clinical effects of acute bacterial meningitis. Stiffness can sometimes be mild or absent. Meningococcal meningitis (most commonly serogroups A, B and C) should be suspected in extremely rapidly evolving meningitis with stupor, delirium and when the onset is associated with petechial or purpuric rash, ecchymosae or shock. Pneumococcal meningitis is often preceded by an infection in the lungs, ears, sinuses, or heart valves and should be suspected in alcoholic, splenectomized patients, elderly, sickle cell patients and basilar skull fracture. HIV infection, hematologic neoplasm and metastatic disease, collagen disorders, immunosuppressive therapy are conditions, which favor invasion by Enterobacteriaceae, Listeria, A. calcoaceticus and Pseudomonas. Focal seizures and stroke can occur. Meningeal signs may be absent in half the patients with Listeria infections and the CSF may show mild abnormalities. All febrile patients even those with low-grade fever and those with only lethargy, headache, or confusion of sudden onset should be subjected to LP. CSF opening pressure <250 mm H2O is likely to be viral meningitis while values in bacterial meningitis range between 200-500 mm H2O. When ICHT is suspected (decreased level of consciousness) a 22-gauge needle LP 30 to 60 min after 1g/kg i.v. mannitol infusion in addition to hyperventilation can be performed. Pleocytosis is diagnostic with leucocytes predominantly neutrophils (90%) ranging from 250 to 10,000/mm3. CSF glucose content < 40 mg/dL (or glucose blood/CSF ratio < 0.4). Protein content is > 45 mg/dL (100-500 mg/dL) in 90% of the cases and CSF lactate is increased in bacterial and fungal meningitis (>35 mg/dL). Gram stain examination of CSF allows a rapid and accurate identification of the causative bacterium (N. meningitides, S. pneumoniae and H. influenza) in about 80% of cases (40% for Listeria) and has a specificity of >97%. CSF culture (sheep blood agar, chocolate agar and broth) is positive in 75% of patients with acute bacterial meningitis but may take up to 48 hours for organism identification. Depending on the bacteria the latex agglutination test sensitivity varies between 50-100% (high sensitivity for H. influenza (60-90%) but less sensitive for N. meningitides, S. pneumoniae, S. agalactiae, E. coli) and may be most efficacious in those patients who have received antibiotic therapy prior to lumbar puncture. Limulus lysate may be useful in suspected case of gram-negative meningitis (endotoxin). A negative limulus test does not rule out the diagnosis of gram-negative meningitis and therefore is not used routinely. PCR has been utilized in meningitis caused by common meningeal pathogens, including N. meningitides, S. pneumoniae, H. influenza type b, S. agalactiae and L. monocytogenes. The diagnostic sensitivity and specificity are 94 and 96%, respectively. Patients with bacterial meningitis should have a repeat LP 24 to 36 hours after to initiation of therapy to document sterilization of the CSF.

Blood cultures should always be obtained because they are positive in 50% of the cases with S. Pneumoniae, N. meningitides and H. influenza. Meningitis may be complicated within a few days by hyponatremia due to SIADH. Brain MRI may be normal or show abnormal signals in the brainstem (rhombencephalomeningitis) in Listeria infection. Recurrent bacterial meningitis should suspect congenital neuroectodermal sinus or sinoidal fistula. Empiric intravenous treatment (ceftriaxone 2 g q12h - with ampicillin 3 g q6h if listeria is suspected - and plus vancomycin 1 g q12h with or without rifampicin in penicillin-resistant pneumococci, and acyclovir if herpes is suspected) should be started while awaiting the results of CSF and blood cultures, and subsequently be adjusted, and should last at least 2 weeks. Prolongation of fever or focal neurologic signs may indicate subdural effusion, mastoiditis, venous sinus thrombosis, cortical vein phlebitis or brain abscess.

Meningoencephalitic syndrome may be caused by Mycoplasma pneumoniae, Listeria monocytogenes, and legionnaires disease.

In peumococcal meningitis and all other acute bacterial meningites with moderate to severe Glasgow coma scale on admission, dexamethasone (10 mg qid) should be given 15 to 20 min before the 1st antibiotic dose and continued for 4 days. This reduces seizure frequency, consciousness level and risk of cardiorespiratory failure, unfavorable outcome, and death. A single i.m. dose of an oily suspension of chloramphenicol has been shown to be as effective in meningococcal meningitis as a 5-day course of crystalline penicillin. This approach is often used during an epidemic in a developing country. Rifampicin 600 mg bid for 2 days or ciprofloxacin 500 mg one single dose or ceftriaxone 250 mg one single dose IM is effective for chemoprophylaxis against meningococcal disease. Vaccination against meningococci covers for A, C, Y and W-135 serogroups and may last up to 10 years.

The mortality rate is around 30% in S. Pneumoniae and 10% in N. meningitides. Death occurs in 40% of patients with seizures.


Aseptic meningitis


Viral meningitis: Viral meningitis (most commonly enterovirus in particular echovirus) is characterized by predominantly lymphocytic pleocytosis with normal CSF glucose and small and variable increase in protein, and positive CSF PCR. An exception to this rule are viral infections with HSV-2lymphocytic choriomeningitis (often also associated with 1000s of lymphocytes) and VZV, which may occasionally display CSF glucose levels between 25 and 40 mg/dl. The diagnosis of viral meningitis is finally based on complement fixation or ELISA techniques by showing a 4x increase in titer from acute to convalescent serum drawn at least with 10 days interval. Viral culture sensitivity is only 70%. HSV-2 aseptic meningitis is the main neurologic complication of HSV-2 infection. HSV-2 causes genital herpes and is in the West the 3rd most common cause of benign recurrent aseptic meningitis, accounting for approximately 5% of all cases. Unlike viral meningitides that have a seasonal association, HSV-2 meningitis occurs at any time of year. Meningitis may be preceded by recent symptoms of pelvic inflammatory disease or associated penile or scrotal pain. Careful search for vesicular lesions over the external genitalia and a pelvic examination for lesions in the vagina or on the cervix should be done. PCR has revealed that the primary agent causing benign recurrent lymphocytic meningitis is HSV-2. HSV-2 meningitis is self-limiting; treatment with acyclovir is not required. Occasionally, HSV-1 is the culprit, as evidenced by the detection by CSF PCR of HSV-1 DNA of patients with benign recurrent lymphocytic meningitis. In contrast, low CSF glucose levels are usually observed in TB (lymphocytic pleocytosis + cranial polyneuropathy + low CSF glucose + fever) and fungal meningitis (particularly in later stages of the disease), neoplastic disease (metastatic carcinoma, lymphoma, meningeal carcinomatosis) (lymphocytic pleocytosis + cranial polyneuropathy + normal or slightly decreased CSF glucose + afebrile), and sarcoidosis of the meninges. Mycoplasma infections, cat-scratch fever and Q fever may also result in aseptic meningitis. HIV meningitis (a sign of seroconversion) may often be associated with cauda equina neuritis. Other viruses include CMV (immunocompromised), mumps (unvaccinated), West Nile fever virus (Americas, Africa, West Asia, Australia, mainland Europe), tick-borne encephalitis (mainland Europe and Asia) and St. Louis encephalitis virus (Southern states of the US). Aseptic meningitis can also be caused by infections thought to be induced by viruses such as Kikuchi-Fujimoro disease (histiocytic necrotizing lymphadenitis).


TB meningitis: TB meningitis is usually a reactivation of a dormant subcortical or meningeal focus. Risk factors for TB meningitis are age, malnutrition, alcoholism, diabetes mellitus, chronic corticosteroid therapy and HIV-1. The clinical presentation of TB meningitis consists of the following triad: low-grade fever (up to 98%), meningeal findings (88%) and focal neurologic signs. TB meningitis is usually indolent, with an insidious prodrome characterized by malaise, fatigue, low-grade fever, intermittent headache, vomiting and personality changes. This is followed by development of meningeal syndrome with 2 to 3 weeks. However both extremes are possible: acute bacterial-like meningitis picture or slowly progressive dementia-like syndrome over months or years. Focal neurologic signs consist of uni-or bilateral cranial nerve palsies (VI > III, IV and VIII). Symptoms of tuberculomas are often limited to fits and papilledema. The mean duration of symptoms is weeks to months. Only 30% of patients with tuberculomas have evidence of tuberculous infection outside the CNS. Chest films show abnormalities in about 50-80% of patients with TB meningitis. ESR and WBC may be normal or slightly increased. CSF opening pressure is increased ranging from 180-300 mm H2O. CSF glucose is usually 40 mg/dL (<2.2 mmol/L) and protein 150 or >200 mg/dL. In 10-20% of cases glucose in CSF is normal. CSF contains usually between 50-500 cells, which may be neutrophils and lymphocytes in equal amounts. Later on lymphocytes predominate. CSF acid–fast smears are positive in 8-86% of patients. CSF cultures are positive in <50% of patients. Increased CSF adenine deaminase levels are a sensitive marker for TB meningitis. PCR for detecting fragments of mycobacterial DNA in CSF specimens is positive in 83-100% of cases. No pathognomonic neuroimages exist for TB of the CNS. MRI (T1) may show hydrocephalus, leptomeningeal enhancement postcontrast administration, medium or small vessel infarction or tuberculomas.

The clinical diagnosis may be considered if the three criteria are positive:  CT scan brain suggestive of hydrocephalus, edema or basal enhancement + positive chest X-ray + good response to clinical therapy.

Irrespective of the results of individual tests, if TB meningitis is seriously suspected, it is far better to start treatment immediately and reconsider the diagnosis when the dust has settled. CSF changes remain positive for a period of 10 to 14 days after therapy has been initiated and may increase despite the therapy. Classical tetra therapy (INH, rifampicin, pyrazinamide, ethambutol or streptomycin) is used, some of them for a prolonged period 18-24 months. Steroids should only be used in case of life-threatening subarachnoidal block or raised intracranial pressure (above 20 mmHg). Up to 30% have severe residual sequelae such as mental impairment, seizures, visual and oculomotor disorders, deafness and hemi- or quadriparesis, the latter often as a result of vasculitis in the vessels of the circle of Willis, the vertebrobasilar arteries, and perforating branches of the middle cerebral artery.

Non-TB mycobacteria or atypical mycobacteria include M. avium, M. kansasii and M. fortuitum.  These can occur in immunocompetent or immunocompromized patients.

Treatment consists of quadritherapy: INH (300 mg od plus 50 mg vitamin B6), rifampicin (600 mg od), ethambutol (800 mg od), pyrazinamide (25 mg/kg/d or 1,500 mg/d) for 3 months followed by 6 months tritherapy. Add dexamethasone 10 mg q6h for 5 days to taper gradually over 2 months if increased intracranial pressure, visual failure, CSF protein > 5 g/l, focal CNS signs or prominent encephalitis. A second LP, 48 hours after the first is justified to assess the response to treatment. 30% of patients die despite anti-TB therapy.


Syphilitic meningitis: This type of meningitis presents with meningismus, headache and fever. Cranial nerve palsies are found in 45% of patients. Meningovascular syphilis is characterized by weeks to months of episodic prodromal symptoms and signs, including headache or vertigo, personality and behavioral changes, insomnia and seizures. In addition focal neurologic deficits occur reflecting the vascular ischemic effects. Both serum RPR and VDRL, and FTA have a specificity of 97 to 99%; RPR sensitivity is 71% and FTA-ABS sensitivity is 96%. The diagnostic requirements for neurosyphilis consist of: reactive VDRL and TPA-ABS tests in CSF with compatible case pleocytosis (CSF WBC count >10/mm3) and CSF protein elevated (> 0.50 g/l). CSF VDRL has low sensitivity (22-69%), and may however be positive in only 30% of late syphilis cases. Due to contamination possibility, a reactive VDRL on CSF in the absence of blood contamination is sufficient to diagnose neurosyphilis, but a nonreactive result does not exclude the diagnosis. Hence a positive VDRL always needs to be confirmed by FTA-ABS. Although nonreactive CSF FTA-ABS test rules out the likelihood of syphilis, the diagnosis of neurosyphilis is still based on elevated CSF WBC (>10/mm3) and/or protein CSF in the appropriate clinical and serologic setting. False-negative syphilis tests occur in patients with HIV infection. Treatment consists of 18 to 24 million IU of intravenous penicillin each day for 10 to 14 days. CSF leukocyte count should decrease within 6 months after therapy. Protein levels are expected to drop at a slower rate and normalize within 2 years. CSF VDRL is also useful for monitoring the effect of antibiotic therapy for syphilis. Although CSF VDRL titers decrease, it may be years before they become nonreactive.


Cryptococcal meningitis: This fungal infection is ubiquitous and occurs most commonly in patients who are immunosuppressed (HIV-1, reticuloendothelial malignancies, sarcoidosis, organ transplantation, collagen vascular disease, diabetes mellitus, chronic hepatic failure, chronic renal failure and patients on corticosteroids). Despite this, healthy individuals can be affected too. 5-10% of AIDS patients develop cryptococcal meningitis. In non-AIDS patients, cryptococcal meningitis is typically a subacute process (days or weeks) consisting of headache, fever, meningismus, and personality change. Ocular abnormalities and cranial nerve palsies are common but usually at later stages. In AIDS patients, the presentation is more subtle sometimes presenting with only headache, fever and lethargy, in the absence of meningeal signs. The CSF opening pressure is usually >200 mm H2O.  Most non-AIDS patients have lymphocytic pleocytosis (20-500 cells/mm3), with occasionally eosinophilia. CSF protein is usually increased and glucose normal or subnormal. In AIDS patients CSF may be normal. CSF India ink examination remains a rapid, effective test that is positive in 50-75% of cases. Latex agglutination test is both sensitive and specific and titers of 1/8 are considered diagnostic. The yield of CSF cultures is very high (96%) but requires long time. Alternatively serum and CSF antigen (90% sensitive) detection can be used. MRI may show hydrocephalus, multiple nonenhancing cystic periventricular masses in the basal ganglia but is often normal. Basilar meninges may enhance after gadolinium administration. CSF should be recultured at the end of 10 weeks.


Coccidioidomycosis meningitis:  Most commonly seen in the southwestern US, the Central Valley of California, northern Mexico, and parts of Central and South America. C. immitis rarely disseminated to CNS. Predisposing factors for dissemination are old age, pregnancy, corticosteroids therapy, antitumoral chemotherapy, immunosuppression, and HIV infection. The meningitis is usually subacute or chronic with patients complaining of headache, low-grade fever, weight loss, and mental status changes. Signs of meningismus are usually absent. CSF findings are typical for fungal meningitis (variable opening pressure, moderately elevated (20-500) WBC counts, elevated protein, low CSF glucose (often < 40 mg/dL), and negative gram stains) and can be sometimes normal. The diagnosis depends upon the demonstration of elevated serum concentrations of complement-fixing antibodies (titers >1/32 to 1/64 suggest dissemination). Occasionally CSF may reveal prominent eosinophilia. CSF cultures are positive in 25-50% of patients with meningitis. Fluconazole is effective therapy for coccidioidal meningitis.


Histoplasmosis meningitis: Histoplasmosis is common in the Mississippi and Ohio river valleys. H. capsulatum may develop without evidence of systemic infection and even in immunocompetent patients. Chronic corticosteroid therapy is a risk factor for disseminated histoplasmosis. Meningitis occurs in 10-20% of patients with disseminated histoplasmosis. The symptoms are headache and fever and occasionally focal neurologic deficits. Mental status abnormalities may occur. Pulmonary lesions may be mild, resolving or asymptomatic. Repeated LP may be required. CSF may show signs of chronic meningitis (raised protein, decreased glucose and lymphocytic pleocytosis). CSF and blood cultures may be negative. Immunological studies include yeast phase and mycelial phase. CSF, serum and urinary histoplasma antigen may provide the diagnosis in cases of dissemination. MRI may show hydrocephalus and meningeal enhancement after gadolinium injection. Brain and meningeal biopsy may be required.


Candida meningitis: Candida species are ubiquitous but infections commonly occurs in patients receiving corticosteroids, broad-spectrum antimicrobial therapy; in patients with  malignancies, neutropenia, sarcoidosis, collagen vascular disease, diabetes mellitus, and in patients with central venous catheters. Candidal meningitis is nonspecific. The onset can be either abrupt or insidious and the clinical manifestations can be differentiated from other forms of fungal meningitis. CSF pleocytosis (600 cells/mm3), lymphocytes or neutrophils. Yeast is detected in 50% of cases on direct microscopy of CSF. A single positive culture from a patient with risk factors or symptoms is considered significant when CSF indices are compatible and the fungus is isolated in pure culture.

Actinomycetes, Nocardia, and pseudallescheria occurs almost exclusively in immunocompromised patients (Hodgkin and non-Hodgkin disease, multiple myeloma, solid tumors, long-term use of steroids, chronic obstructive pulmonary disease, alveolar proteinosis, SLE, vasculitis, Cushing disease, chronic liver disease, hemochromatosis, RA, sarcoidosis, TB, diabetes, alcoholism, chronic granulomatous disease, solid organ or bone marrow transplantation, AIDS). Pseudallescheria boydii presents as brain abscess and occasionally as meningitis. The infection becomes manifest 2-3 weeks after an episode of near drowning. Biopsy is diagnostic. Nocardia results in 70% from lung infections. In the presence of nocardia meningitis (CSF show pleocytosis (83%), reduced glucose (64%) and protein >100 (61%)) brain abscesses may result in 20-40% of cases.


Primary amebic meningoencephalitis: Exposure to contaminated pools and water may result in infections with amoebae (Naegleria fowleri and Acanthamoeba). In the acute form, following an incubation period of 3-8 days, there is sudden onset of high fever, photophobia and headache with or without focal neurologic signs. CSF shows neutrophilic pleocytosis, low glucose and elevated protein and red blood cells. Examination of fresh warm specimens of CSF can reveal trophozoites. The subacute or chronic form presents more insidiously, with low-grade fever, headache, and focal neurologic signs. CSF shows predominantly mononuclear cells, normal or subnormal glucose and elevated protein. Serum immunofluorescence amebic immobilization titers and complement-fixing antibodies support the diagnosis. Deterioration occurs over weeks or months can occur.


Toxoplasma encephalitis: CNS toxoplasmosis is usually associated with intracerebral mass lesions or encephalitis in immunocompromised hosts (lymphoma, leukemia, cytotoxic therapy, organ transplantation, treatment of collagen disorders, HIV patients). The clinical manifestations of CNS toxoplasmosis range from insidious onset evolving over weeks to an acute confusional syndrome. Transplant patients often have diffuse and disseminated disease. Early signs and symptoms include weakness, lethargy, confusion, seizures and headache. AIDS patients with CNS toxoplasmosis often present with nonspecific symptoms such as neuropsychiatric complaints, headache, lethargy and confusion. The course is progressive over 2 – 8 weeks. Patients then develop evidence of focal CNS mass lesions. The parasite has a predilection to localize in the basal ganglia, producing an akinetic–rigid syndrome. AIDS patients often develop a chronic encephalopathy with seizures. In AIDS patients, more than 97% of patients with toxoplasmosis encephalitis have serum antibody titers against T. gondii ranging from 1:8 to >1:1,024. Brain CT scan shows multiple rounded isodense or hypodense lesions with ring enhancement after contrast administration affecting particularly the basal ganglia or corticomedullary junction. MRI is more sensitive and is able to demonstrated diffuse toxoplasmic encephalitis. Definitive diagnosis is based on brain biopsy with demonstration of the pseudocysts and tachyzoites. In AIDS patients, positive neuroimaging and positive anti-Toxoplasma IgG serologic tests are sufficient to initiate empiric therapy for toxoplasmic encephalitis. Negative serologic test makes the diagnosis less likely and warrants brain biopsy.


Angiostrongylus cantonensis: This infection leads to eosinophilic meningitis. This parasite is ubiquitous in South East Asia. Typical symptoms of meningitis start 6-30 days after ingestion of raw mollusks. Eosinophilia is found in blood and CSF.


Uveoretinal meningoencephalitis: This form of meningitis may occur in several conditions: a. Inflammatory diseases: 1) SLE; lupus choroidopathy occurs with significant vasculitis, renal complications (including systemic hypertension), and rarely is associated with retinal pigment epithelial disease or secondary retinal detachment; 2) Sarcoidosis: patients may have uveitis and meningoencephalitis with hypothalamic involvement. The uveitis is usually anterior rather than posterior. Moreover, retinal detachment is unusual; 3) Ocular lyme borreliosis: can present with iridocyclitis, vitreitis, and occasionally panuveitis and retinal detachment; 4) Other inflammatory diseases: including MS, neuroBehçet and inflammatory bowel disease; b. Infectious diseases: 1) Syphilis: uveitis, chorioretinitis, and optic neuritis are late manifestations; 2) Tuberculosis: Retinal changes are limited to "multifocal" granulomas, large or small; 3) HSV and VZV can cause uveitis, conjunctivitis, keratitis, and encephalitis follow ophthalmic zoster. HSV intraocular disease is usually a necrotizing retinitis; 4) Whipple disease; 5) Fungal infections; 6) Other: HIV meningitis can cause a similar clinical picture with acute meningitis 3-6 weeks after the primary infection, but the eye findings are varied (cotton-wool spots being the most common). CMV causes retinitis and encephalitis in immunocompromised patients. The same argument follows for toxoplasmosis; c. Eye/CNS diseases: 1) Sympathetic ophthalmia can present with rapid bilateral visual loss associated with anterior segment inflammation, disk edema/hyperemia, choroidal thickening, and serous retinal detachments; 2) Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an acute condition occurring in both men and women from 15-50 years of age classically in the recovery phase after a viral illness and is characterized by loss of central vision associated with the appearance of multiple pale lesions in the retinal pigment epithelium. The patients may occasionally have papillitis and serous detachment of the retina or CNS involvement with headache, transient ischemic attacks, dysacusis and tinnitus. It is a self-limited disease, resolving in 2 to 3 weeks; 3) Multifocal secondary retinal and pigment epithelial detachments are also seen in (Grade IV) systemic hypertension, and pregnancy-induced hypertension; 4) Vogt-Koyanagi-Harada syndrome a recurrent form of aseptic meningitis consists of bilateral, rapid, and painful loss of vision associated with posterior or panuveitis. It is associated with meningitis, dysacusis, tinnitus, uveitis, or cerebrospinal fluid pleocytosis and much later with depigmentation of the uveal tract and skin (alopecia, poliosis, or vitiligo (late)). There is a slight preponderance of females. The age of onset is usually between the 2nd and 5th decades, with a mean age of 30 to 40 years. Multifocal and multiloculated serous pigment epithelial and retinal detachments are seen on ophthalmoscopic exam and documented on fluorescein angiography.


Carcinomatous meningitis: Meninges are involved in 5-15% of all patients with solid or hematological tumors: (leukemia (40%), breast (34%), lymphoma (30%), lung (26%), melanoma (25%) and gastrointestinal (9%). About one third of patients with meningeal carcinomatosis have cranial nerve involvement, but less than 50% of patients have nuchal rigidity, headache or vomiting. MRI (T1) reveals diffuse dural meningeal enhancement (50-90%) and CSF in over 50% of cases elevated protein and reveals aseptic meningitis. CSF cytology is positive in only 50% of cases. Useful tumor makers in CSF are CEA (breast, lung, gastrointestinal tumors), epithelial membrane antigen, β-glucuronidase, β2-microglobulin, and lactate dehydrogenase.