Primary melanotic tumors of the nervous system: a consecutive case series.

BACKGROUND AND PURPOSE: Primary melanotic tumors of the nervous system (PMTNS) are thought to be an exceedingly rare group of tumors not captured by tumor registries. We aimed to determine relative incidence, clinical presentation, diagnostic findings, patient management, and outcome. METHODS: We retrospectively searched the database of the Section of Neuro-Oncology at the Yale Cancer Center for patients with primary or metastatic melanotic lesions of the nervous system. For patients with PMTNS, we recorded demographic data, clinical presentation, histopathological and imaging findings, therapy, and outcome. RESULTS: A total of 116 patients with melanotic lesions were identified, including four patients with PMTNS. The relative incidence of PMTNS was therefore calculated as 3.4%. Histology of PMTNS patients revealed melanocytoma in three patients and psammomatous melanotic schwannoma in one patient. Symptoms were non-specific and attributed to tumor mass effect. Magnetic resonance imaging showed hyperintensity on pre-contrast T1-weighted imaging, hypointensity on T2-weighted imaging, and homogenous contrast enhancement in all PMTNS patients. Definitive diagnosis was based on tissue analysis, with detection of melanin-containing cells on conventional histology and S100-positivity on immunohistochemistry. Molecular analysis for GNAQQ209L mutation assisted in establishing diagnosis when only small amounts of tissue were available. Aggressive surgical treatment showed favorable outcomes in all cases; radiation therapy was used for residual or relapsed disease. The median follow-up was 7.5 ± 5 years, and all patients were alive on the day of database closure. CONCLUSION: Primary melanotic tumors of the nervous system are rare nervous system tumors. Outcome appears excellent, and complete surgical resection may form the basis for favorable outcome. Radiation therapy may represent a therapeutic approach for residual or relapsed disease.

Short echo spectroscopic imaging of the human brain at 7T using transceiver arrays.

Recent advances in magnet technology have enabled the construction of ultrahigh-field magnets (7T and higher) that can accommodate the human head and body. Despite the intrinsic advantages of performing spectroscopic imaging at 7T, increased signal-to-noise ratio (SNR), and spectral resolution, few studies have been reported to date. This limitation is largely due to increased power deposition and B(1) inhomogeneity. To overcome these limitations, we used an 8-channel transceiver array with a short TE (15 ms) spectroscopic imaging sequence. Utilizing phase and amplitude mapping and optimization schemes, the 8-element transceiver array provided both improved efficiency (17% less power for equivalent peak B(1)) and homogeneity (SD(B(1)) = +/-10% versus +/-22%) in comparison to a transverse electromagnetic (TEM) volume coil. To minimize the echo time to measure J-modulating compounds such as glutamate, we developed a short TE sequence utilizing a single-slice selective excitation pulse followed by a broadband semiselective refocusing pulse. Extracerebral lipid resonances were suppressed with an inversion recovery pulse and delay. The short TE sequence enabled visualization of a variety of resonances, including glutamate, in both a control subject and a patient with a Grade II oligodendroglioma.

Delayed leukoencephalopathy with stroke-like presentation in chemotherapy recipients.

BACKGROUND: A transient leukoencephalopathy mimicking cerebrovascular accident has been described as a complication of chemotherapy, most commonly in recipients of intrathecal methotrexate for childhood leukaemia. Recently published neuroimaging data suggest a common pathophysiology associated with a variety of chemotherapy agents and modes of administration. METHODS: We reviewed the medical literature for single reports and case series of patients presenting with stroke-like episodes while receiving systemic or intrathecal chemotherapy. We only included studies providing detailed neuroimaging data. Patients with cerebrovascular accidents were excluded. RESULTS: We identified 27 reports of toxic leukoencephalopathy in patients treated with methotrexate (intrathecal, systemic), 5-fluorouracil and its derivative carmofur, and capecitabine. Diffusion weighted imaging (DWI) of all patients revealed well demarcated hyperintense lesions within the subcortical white matter of the cerebral hemispheres and the corpus callosum, corresponding to areas of decreased proton diffusion on apparent diffusion coefficient (ADC) maps (available in 21/27 patients). Lesions exceeded the confines of adjacent vascular territories. Complete resolution of symptoms within 1-4 days was accompanied by normalisation of ADC abnormalities. However, fluid attenuated inversion recovery (FLAIR) sequences frequently revealed persistent white matter abnormalities. CONCLUSIONS: Several pathophysiological models of delayed leukoencephalopathy after exposure to intrathecal or systemic chemotherapy have been proposed. DWI findings in this cohort are indicative of cytotoxic oedema within cerebral white matter and lend support to an at least partially reversible metabolic derangement as the basis for this syndrome.

Multiple strokes and bilateral carotid dissections: a fulminant case of newly diagnosed Ehlers-Danlos syndrome type IV.

Ehlers-Danlos Syndrome is a rare group of inheritable disorders resulting in abnormal collagen production, leading to skin fragility, joint hypermobility and easy bruising. Six major subtypes have been identified, of which Type IV most often leads to neurovascular complications, may lead to inner organ rupture and overall has the worst prognosis. Early recognition followed by genetic testing is key, since this diagnosis will guide decision making in the management of complications, influence the choice of antiplatelet medications versus anticoagulants and allow for potentially affected family members to be identified, undergo genetic testing and reproductive counseling. We here report the case of a 50 year old woman with a fulminant presentation of Ehlers Danlos Syndrome Type IV, including bilateral carotid and vertebral artery dissection, multiple strokes and liver rupture. Of note, this patient did not have a known history or obvious clinical features of connective tissue disease. Genetic testing confirmed the diagnosis. Review of her family history revealed multiple family members with a history of aortic dissection or aneurysm rupture. This case illustrates that Ehlers Danlos Syndrome Type IV is an important differential diagnosis even in adult patients without a known history of connective tissue disease and no prior complications.

Diffusion-weighted MRI correlates of subacute methotrexate-related neurotoxicity.

OBJECTIVES: A delayed stroke-like leukoencephalopathy has been observed in patients receiving methotrexate (MTX) for childhood leukemia. Diffusion-weighted MRI (DWI) may help to distinguish between ischemic stroke and chemotherapy-related leukoencephalopathy. Although conventional MRI correlates have been described for this stroke-like syndrome, DWI data are largely unavailable. Our objective is to present a retrospective analysis of the DWI findings in four patients who suffered subacute neurotoxicity after intrathecal MTX. DESIGN: We reviewed the medical records of four patients, who were seen by us between July 2000 and February 2004 for sudden onset of a central neurological syndrome within days of intrathecal MTX. Patients underwent standardized MRI within 48 h of symptom onset; MRI included DWI and apparent diffusion coefficient (ADC) maps. RESULTS: DWI of all patients revealed well-demarcated hyperintense lesions within the subcortical white matter corresponding to areas of restricted proton diffusion on ADC maps. Lesions exceeded the confines of adjacent vascular territories. Complete resolution of symptoms within 1-4 days was accompanied by normalization of ADC abnormalities. CONCLUSIONS: DWI findings in this cohort seem to reflect cytotoxic edema within cerebral white matter suggesting a reversible metabolic derangement, rather than ischemia, as the basis for this syndrome.

Intravascular lymphoma: magnetic resonance imaging correlates of disease dynamics within the central nervous system.

BACKGROUND: Intravascular lymphoma (IVL) is a rare non-Hodgkin's lymphoma with relative predilection for the central nervous system. In the absence of extraneural manifestations, the disease is not recognised until autopsy in the majority of cases underlining the need for new clinical markers. METHODS: This is a retrospective series of five patients with IVL seen at a single institution over three years. An advanced magnetic resonance imaging (MRI) protocol was performed at various time points prior to diagnosis and during treatment. RESULTS: MRI revealed multiple lesions scattered throughout the cerebral hemispheres; the brainstem, cerebellum, and spinal cord were less frequently involved. On initial presentation, hyperintense lesions were seen on diffusion weighted images suggestive of ischaemia in three of four patients in whom the images were obtained at that time point. In four patients lesions were also identifiable as hyperintense areas on fluid attenuated inversion recovery (FLAIR) sequences. Initial contrast enhancement was encountered in three cases. Diffusion weighted imaging lesions either vanished or followed the typical pattern of an ischaemic small vessel stroke with evolution of abnormal FLAIR signal followed by enhancement with gadolinium in the subacute stage and tissue loss in the chronic stage. Diffusion weighted imaging and FLAIR abnormalities proved to be partially reversible, correlating with the response to chemotherapy. CONCLUSION: We provide the first detailed description of the dynamic pattern of diffusion weighted MRI in IVL. These patterns in combination with systemic findings may facilitate early diagnosis and serve as a new tool to monitor treatment response.

Malignant fibrous histiocytoma presenting as an intraventricular mass five years after incidental detection of a mass lesion.

Malignant fibrous histiocytoma is a rare intracranial neoplasm. It usually presents as a meningeal mass but occurs also intraaxially. Few information is available on cellular origin, premalignant histologic stages and time course of malignant transformation. We report a case of a primary intraventricular malignant fibrous histiocytoma in a patient who five years prior to clinical manifestation of the malignancy was found to have an intraventricular mass with benign CT characteristics.