Idiopathic intracranial hypertension (IIH), or pseudotumor cerebri, is a clinical syndrome characterized by headache and increased intracranial pressure, with no focal neurologic signs except for abducens nerve paresis and without any evidence on neuroimaging of structural brain disease, including the lack of ventriculomegaly (1–3). One of the accepted diagnostic criteria strictly specifies normal cerebrospinal fluid (CSF) composition. If white blood cells are found in the CSF, the working diagnosis is meningitis and diagnostic efforts are focused on finding a primary cause for the intracranial hypertension to introduce specific treatment. Although IIH has been associated with diverse etiologic factors, in many instances the association is circumstantial rather than causal, and the mechanism responsible for this condition remains elusive (2). In the majority of patients with IIH, no cause can be identified.
Within the past few years, we have encountered several patients who have fulfilled the criteria required for the diagnosis of IIH except for the presence of CSF pleocytosis. An extensive workup for the cause or origin of the disease did not yield any underlying abnormality, and the patients followed a clinical course typical of IIH. All responded to pharmacological or surgical therapies recommended for the treatment of IIH. The aim of the present report is to draw attention to a disorder of chronic meningitis that mimics the course of IIH and, despite intense diagnostic efforts, remains idiopathic and resolves with treatment that is neither anti-infectious nor anti-inflammatory.
We reviewed the files of all patients who were hospitalized with the diagnosis of IIH from January 1991 to December 1999 in the departments of neurology of Sheba Medical Center, Tel Hashomer (Tel Aviv, Israel) and Hadassah-Hebrew University Hospital (Jerusalem, Israel). All patients who had CSF pleocytosis were identified and included in the present study. For these patients, data were collected from patient charts, including gender, age at presentation, obesity, symptoms and signs, CSF findings on presentation, results of diagnostic workup, and clinical course.
Over a nine-year period, six patients were identified with a clinical picture typical of IIH except for the presence of CSF pleocytosis. There were five women and one man. Mean age at presentation was 25.7 years (range, 17–32 yr). Mean follow-up was 33 months (range, 14–55 mo). Clinical data are summarized in Table 1.
All patients were obese, as defined by body mass index greater than 30 kg/m2. Otherwise, none had associated medical conditions or identifiable risk factors for IIH. All were afebrile throughout the clinical course. Upon presentation, all patients but one had bilateral swollen discs. All patients had elevated opening CSF pressures (range, 380–500 mm H2O) and normal CSF glucose and protein values.
The average number of white blood cells in the CSF on presentation was 77 cells/μL (range, 16–152 cells/μL). In #1, 4, 5, and 6, all cells were lymphocytes; in one patient (#2), 90% were lymphocytes; and in one patient (#3), the CSF contained predominantly polymorphonuclear leukocytes and a few lymphocytes. Five of the six patients had at least one additional CSF examination performed one to seven weeks after the initial spinal tap and performed as late as seven months after presentation (#1). Cerebrospinal fluid pleocytosis persisted in all repeated examinations, with a tendency to decrease in magnitude over time.
All patients underwent a thorough laboratory evaluation (Table 2). In none of the patients did it reveal a primary central nervous system or a systemic cause for the clinical picture.
Computed tomography scans of the brain and orbits were normal in all patients. Brain magnetic resonance imaging in four (#1, 3, 6, and 7) and magnetic resonance venography in one patient (#6) did not identify any cerebral or meningeal abnormalities (including enhancement).
Treatment with 250 mg acetazolamide every six hours resulted in prompt symptomatic relief in three patients (#2, 3, and 6) and gradual improvement over a period of several months in two (#4 and 5). These five patients remained asymptomatic following withdrawal of therapy after four to 12 months. The one man (#1) did not respond adequately to medical treatment, requiring lumboperitoneal shunt.
In the present study, we report six patients who had chronic or subacute meningitis with intracranial hypertension and for whom the cause of CSF pleocytosis remained unexplained. Viewed alternatively, for these patients the criteria required for the diagnosis of IIH were met except for CSF pleocytosis because they presented with headache and papilledema without focal neurologic signs and neuroimaging did not disclose any intracranial abnormality. None of the patients had systemic symptoms or signs of an infectious or an inflammatory process. All underwent a comprehensive workup that did not disclose an infectious, inflammatory, or malignant cause during a mean follow-up period of 33 months.
Our patients had age and sex attributes typical for IIH. All had a course that resembles that of IIH, with five patients responding favorably to treatment with acetazolamide and one patient improving after lumboperitoneal shunt.
The pathogenesis of IIH is unknown. The syndrome may be due to an imbalance between the formation and the egress of CSF or a result of inability of intracranial structures, such as brain parenchyma and blood vessels, to accommodate increased volumes of CSF (1). Many conditions have been associated with the occurrence of the disorder, and in some, a cause-and-effect relationship has been established by clinical recovery following withdrawal of an exogenous causative agent and relapse upon repeat exposure (1).
Especially relevant are systemic conditions associated with the occurrence of IIH that are also capable of causing meningitis. Examples of such possible primary causes for IIH include several inflammatory, immune-mediated, or infectious disorders, such as systemic lupus erythematosus (4), Behçet disease (5), human immunodeficiency virus (HIV) infection (6), and Lyme disease (7). IIH has also been reported in epidemics following viral infection without meningitis (8). However, although all these diseases are recognized causes of meningitis, the cited case reports have not documented CSF pleocytosis.
CSF pleocytosis accompanies systemic infections with nervous system involvement in HIV infection (9), Lyme disease (10), and cryptococcal meningitis (11) and in association with sinusitis (12), but in none of these conditions has IIH been described. The pathogenetic mechanism linking the meningitis in the presented cases and the increased intracranial pressure is unclear. Both could be the independent outcome of a primary systemic condition. As an alternative, the meningitis could be the primary event and contribute to the occurrence of IIH by several mechanisms (such as impeding CSF absorption at the arachnoid villi). Considering that all patients were overweight, which is a known risk factor for IIH, it might be possible that obese patients are predisposed to develop IIH in some cases of meningeal inflammation. Whatever the mechanism, the presenting symptoms and the course of the disease in our patients are typical of IIH, and in all patients therapy for increased intracranial pressure and not for the meningitis led eventually to recovery.
Our series adds another syndrome to the list of conditions simulating IIH. Unquestionably, the presence of meningitis in such patients calls for an intensive evaluation to rule out an infectious, immune-mediated, or malignant underlying condition. However, when no cause for meningitis can be determined and the condition is chronic, we suggest that such idiopathic cases be treated as IIH. The term “pseudo pseudotumor cerebri” might be used to describe these patients. The association between meningitis and increased intracranial pressure may contribute to our understanding of the mechanisms responsible for IIH.
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