Idiopathic intracranial hypertension (IIH) or pseu- dotumor cerebri is manifested in its classic form by continuous headache, visual disturbance, and hearing of intracranial noises, in the absence of localizing signs.1,2 Epileptic seizures seldom occur.1,2 Although papilledema is the clinical hallmark of IIH, this condition may present without papilledema, with unilateral asymptomatic papilledema, or exceptionally, with pseudopapilledema.3-5 Idiopathic intracranial hypertension has been reported in association with endocrine disorders (diabetes, thyroid, parathyroid, obesity), hypertension, and iron deficiency anemia, and after chronic intake of various drugs (antibiotics, multivitamins, vitamin E, oral contraceptives, iron supplements).2,6 An increased incidence of prothrombotic abnormalities, including presence of anticardiolipin antibodies, antithrombin III deficiency, thrombocytosis, polycythemia, and hyperfibrinogenemia, are found in up to a third of patients with IIH.7 A patient with hemophilia A and IIH of many years' duration is described. Cognitive disturbance and headache without visual symptoms manifested his bouts of intracranial hypertension.
Objective.—A patient with hemophilia A and long-standing recurrent symptoms of idiopathic intracranial hypertension is described. During his relapses, he experienced headache, and attention and language disturbance, but no visual symptoms.
Background.—Hemophilia A is a rare inherited coagulation disorder secondary to factor VIII deficiency. Idiopathic intracranial hypertension has been reported in association with prothrombotic conditions and iron deficiency anemia, but not in patients with hemophilia A. Recurrent or chronic headache is not a typical symptom of hemophilia, but headache is a presenting sign of intracranial bleed in persons with hemophilia.
Methods.—Medical history review, clinical neurologic examination, brain magnetic resonance imaging, computed head tomography, and electroencephalogram were performed.
Results.—Neurologic examination revealed bilateral papilledema during relapses of idiopathic intracranial hypertension. Multiple lumbar punctures preceded by the intravenous administration of factor VIII early in the course of the illness confirmed the presence of elevated cerebrospinal fluid pressures and absence of subarachnoid blood. He had no complications from lumbar punctures. Initial electroencephalograms showed background slowing but later normalized. Magnetic resonance imaging of the brain and computerized tomography of the head were normal. Relapses of idiopathic intracranial hypertension were eventually controlled with the administration of acetazolamide.
Conclusion.—Idiopathic intracranial hypertension may develop in patients with hemophilia A in the absence of visual symptoms. Therapeutic and diagnostic lumbar punctures were safe to perform on this patient, following the administration of factor VIII.
idiopathic intracranial hypertension
A 17-year-old adolescent boy was referred to the neurologist because of seizures that began during childhood. He had atonic, absence, and grand mal seizures. His last seizure was 5 years earlier. They had been controlled with carbamazepine, 700 mg per day. He had hemophilia A and chronic hepatitis B and C. He required transfusions with factor VIII intermittently for spontaneous subcutaneous and intra-articular hemorrhages. He had been diagnosed with IIH during childhood because of episodes of nonparoxysmal but intense headache, problems concentrating, language disturbance, personality change, and bilateral papilledema, without visual symptoms. He was not obese and had no history of head trauma. Early in the course of the illness, eight lumbar punctures (LPs) were done in the lateral decubitus position, following standard procedure for diagnostic and therapeutic purposes and after the prophylactic administration of intravenous factor VIII concentrate at a dose of 50 U/kg.
Lumbar punctures confirmed the presence of elevated opening cerebrospinal fluid (CSF) pressures that fluctuated around 280 to 290 mm of water. Closing CSF pressures were variable but in the normal range. Symptoms improved temporarily after LPs until sustained improvement took place. His CSF studies were otherwise normal, with no pleocytosis, normal protein, and no evidence of subarachnoid blood. Several electroencephalograms (EEGs) showed background slowing. General physical examination was normal.
Neurologic examinations were unremarkable except for bilateral papilledema (Figure 1), poor attention span, word-finding difficulties, and flat affect during his relapses. His visual fields were normal. There was no nuchal rigidity. A complete blood count, clinical chemistry profile, liver function tests, and vitamin A serum levels were normal. Carbamazepine levels were therapeutic. Computed tomography of the head and magnetic resonance imaging (MRI) of the brain were normal, showing no signs of subarachnoid hemorrhage or cerebral venous thrombosis. Magnetic resonance angiography was not performed. His most recent EEG was normal. Carbamazepine was slowly discontinued with no seizure recurrence after 3 years of follow-up. Recurrent symptoms of IIH were controlled with the chronic administration of acetazolamide, 500 mg, twice a day. One episode of hip hemarthrosis was treated with an infusion of factor VIII.
Hemophilia A or classic hemophilia is a rare X-link recessive hereditary disorder, manifested by recurrent spontaneous and posttraumatic hemorrhages, secondary to deficiency of factor VIII coagulant protein.8,9 After von Willebrand disease, it is the most frequent congenital bleeding disorder, affecting approximately 1 in 10 000 males.8,9 Although bleeding in patients with hemophilia A may occur anywhere in the body including the central nervous system (CNS), the most common sites are the joints, muscles, and gastrointestinal tract. Periarticular and cranial vault hematomas cause hemophilic pseudotumor (“pseudotumor extracerebri”).10 Chronic headache and IIH are not clinical features of hemophilia A, although 50% of persons with hemophilia with acute intracranial hemorrhage will present with a headache.11 Seizures may complicate the therapeutic administration of intravenous factor VIII or of intranasal desmopressin acetate.12 Lumbar punctures can be safely performed in patients with hemophilia A, if pretreated with factor VIII. The present patient had serial therapeutic and diagnostic LPs during childhood after prophylactic administration of intravenous factor VIII, without complications. Silverman et al reviewed the literature and concluded that the risk for serious complication of LPs in persons with hemophilia ranges from 0% to 5.8%.13 Wilson et al encountered brain abnormalities in a group of 124 children and adolescents with hemophilia that were studied with MRI.14 The overall rate of abnormalities was 20.2%. Five patients had posterior fossa congenital CSF cysts and 14 had acquired lesions consisting of single or multiple high-intensity white matter signals on T2-weighted imaging.14 The subject of the present report had no intracranial lesion that could have explained his symptoms on basis of a different mechanism than IIH including the presence of cerebral venous thrombosis.
The pathogenesis of IIH is based on the elevation of intracranial venous pressure, or increased intra-abdominal and cardiac filling pressures, eventually causing retrograde elevation of CSF pressure.15,16 Jacobson et al recently encountered increased serum vitamin A levels in 16 women with IIH.17 These abnormalities were independent of the presence of obesity. Idiopathic intracranial hypertension in patients with elevated circulating levels of vitamin A is explained by putative membranolytic damage of the arachnoidal granulations of the superior sagittal sinus by lipoprotein-bound retinol. This occurs when the capacity of the retinol-binding protein or the hepatic storage of vitamin A is exceeded.17 The patient described here had no intracranial venous pressure measurements, but had normal serum vitamin A levels. Finally, Tugal et al reported a 14-year-old patient with severe iron deficiency anemia accompanied by IIH and summarized the findings in four similar patients published earlier.6 Although this patient had no anemia, a primary CNS disorder of iron metabolism could not be entirely ruled out without first measuring CSF ferritin and transferrin levels.18 Of interest is the patient's absence of visual symptoms during his relapses; instead, he had striking, but nonspecific, cognitive derangement, personality change, and aphasia. Winner and Bello previously reported in this journal a unique case of IIH exhibiting no visual symptoms and no papilledema.19