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Uncommon Presentations of Uncommon Conditions

Pruitt, Amy MD

doi: 10.1097/WNO.0b013e318235f553

Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania.

Address correspondence to Amy Pruitt, MD, Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104; E-mail:

The author reports no conflicts of interest.

Neuro-ophthalmologists evaluate patients who often baffle other physicians due to unusual presentations of uncommon conditions. Vigilance and suspicion of even minor atypical clinical findings or subtle imaging abnormalities are desirable professional traits. Three articles (1–3) in this issue of the Journal illustrate such uncommon dilemmas and provide instructive caveats.

Zunz et al (1) present a pediatric case of gliomatosis cerebri (GC) initially diagnosed as idiopathic intracranial hypertension (IIH). The child's age was in the demographic in which approximately 50% of IIH patients are male and also in the appropriate demographic for pediatric GC. No seizures or focal deficits hinted at a more typical presentation of GC. We are not told the patient's body mass index, although fewer children with IIH are obese when compared to the adult population. At initial presentation, the results of patient evaluation met the criteria for IIH with bilateral papilledema, a sixth nerve palsy, and normal lumbar puncture results save for elevated opening pressure. Mindful that secondary causes of IIH are more common in pediatric than adult patients (4), the authors attempted to exclude the most treatable mimes of IIH, including cerebral venous sinus thrombosis and infiltrating neoplasm. Initial neuroimaging with CT and CT venography was unremarkable. One month later, when MRI and magnetic resonance venogram (MRV) were performed, only subtle imaging clues pointed to a diagnosis other than IIH.

Histologic diagnosis of GC is essential as new techniques offer additional information of prognostic and possibly therapeutic significance. Mitotic index was high in this patient, signifying aggressive tumor behavior. Although not discussed in the report by Zunz et al (1), the presence of mixed oligodendrocytes may confer a better prognosis, particularly when the genetic alteration 1p/19q codeletion is present. For such patients, initial use of temozolomide chemotherapy may be an option and whole brain radiation can then be deferred until later in the clinical course. Recently, isocitrate dehydrogenase 1 and 2 (IDH 1 and IDH 2) mutations were identified in adult glioblastomas with better prognosis (5). The mutations are not seen in primary glioblastoma but occur in 75% of other adult diffuse astrocytic and oligodendroglial tumors (6). The IDH 1 genetic alteration, seen only in adult patients in a study of GC that included 3 pediatric GC cases, conferred a trend toward longer overall survival (10.5 months in nonmutated vs 43.5 months in mutated GC) (7). GC usually behaves aggressively even when histologic features of high-grade astrocytic tumor are absent. The prognosis among children is 64% with 2-year overall survival (8), approximately the same as adults (9). The impact of adjuvant temozolomide for GC appears to improve survival in some early small studies (10).

Noval et al (2) describe neuro-ophthalmic findings in 24 cases of primary diffuse leptomeningeal gliomatosis (PDLG) without brain parenchymal disease. PDLG has a short aggressive course but initially may cause only nonlocalizing signs and symptoms including headache, altered mental status, papilledema, and sixth nerve palsies. MRI shows nodular meningeal enhancement and communicating hydrocephalus mimicking chronic infectious meningitis with hypoglycorrhachia. If spinal fluid cultures are uninformative, meningeal biopsy may be necessary. The 2 index cases reported by Noval et al (2) make a plausible case for tuberculosis (TB) meningitis, and with institution of steroids along with anti-TB medications, there was transient clinical improvement. However, the patients survived only 5–22 months. Of the 24 cases reviewed, the 3 patients who survived more than 1 year all received corticosteroids, temozolomide, and radiation therapy.

Occasionally, patients with leptomeningeal gliomatosis develop GC (11). This may become more frequent with the new recurrence pattern of brain tumors in patients treated with antiangiogenic agents, such as bevacizumab. Preclinical studies suggest that antiangiogenic therapies promote glioma invasiveness and up to 30% of recurrences may be nonenhancing multilobar infiltrative tumor similar to GC or leptomeningeal dissemination. The combination of headache, sixth nerve palsies, and visual loss in these patients undoubtedly will prompt many referrals for neuro-ophthalmic evaluation (12).

Sudhakar et al (3) confront the great neuro-oncologic mimicker, primary central nervous system lymphoma (PCNSL), and use diffusion-weighted imaging (DWI) to assist in the diagnosis of lymphomatous infiltration of the optic nerve. Their patient developed sudden painful complete loss of vision in the right eye 4 months following the diagnosis of non-Hodgkin B-cell Burkitt-type lymphoma and after 4 cycles of chemotherapy. DWI with apparent diffusion coefficient (ADC) maps was consistent with restricted diffusion. Cerebrospinal fluid (CSF) flow cytometry and cytomorphology were positive for a B-cell neoplasm. While cytologic examination of the CSF was normal 4 months after intrathecal and systemic chemotherapy, vision remained poor, and MRI showed decreased enhancement but persistent restricted diffusion of the right optic nerve. The authors suggest that the duration of the ADC abnormality is atypical for ischemia and possibly due to increased tumor cellularity. This is consistent with prior observations that parenchymal PCNSL is distinguished from glioblastomas by a low signal ADC map images (13).

In summary, these 3 articles together illustrate the utility of diagnostic neuroimaging, CSF cytology, and ultimately tissue biopsy. More importantly, the authors demonstrate that clinical acumen is paramount with a high index of suspicion driving repeat evaluations to provide the most accurate information for timely appropriate therapy in difficult diagnostic situations.

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© 2011 Lippincott Williams & Wilkins, Inc.