Numa R. Gottardi-Littell

Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project

Rituximab improves outcomes for persons with lymphoproliferative disorders and is increasingly used to treat immune-mediated illnesses. Recent reports describe 2 patients with systemic lupus erythematosus and 1 with rheumatoid arthritis who developed progressive multifocal leukoencephalopathy (PML) after rituximab treatment. We reviewed PML case descriptions among patients treated with rituximab from the Food and Drug Administration, the manufacturer, physicians, and a literature review from 1997 to 2008. Overall, 52 patients with lymphoproliferative disorders, 2 patients with systemic lupus erythematosus, 1 patient with rheumatoid arthritis, 1 patient with an idiopathic autoimmune pancytopenia, and 1 patient with immune thrombocytopenia developed PML after treatment with rituximab and other agents. Other treatments included hematopoietic stem cell transplantation (7 patients), purine analogs (26 patients), or alkylating agents (39 patients). One patient with an autoimmune hemolytic anemia developed PML after treatment with corticosteroids and rituximab, and 1 patient with an autoimmune pancytopenia developed PML after treatment with corticosteroids, azathioprine, and rituximab. Median time from last rituximab dose to PML diagnosis was 5.5 months. Median time to death after PML diagnosis was 2.0 months. The case-fatality rate was 90%. Awareness is needed of the potential for PML among rituximab-treated persons.

Presenilins Mutated at Asp-257 or Asp-385 Restore Pen-2 Expression and Nicastrin Glycosylation but Remain Catalytically Inactive in the Absence of Wild Type Presenilin

The Presenilins are part of the γ-secretase complex that is involved in the regulated intramembrane proteolysis of amyloid precursor protein and other type I integral membrane proteins. Nicastrin, Pen-2, and Aph1 are the other proteins of this complex. The Presenilins probably contribute the catalytic activity to the protease complex. However, several investigators reported normal Aβ-peptide generation in cells expressing Presenilins mutated at the putative catalytic site residue Asp-257, contradicting this hypothesis. Because endogenously expressed wild type Presenilin could contribute to residual γ-secretase activity in these experiments, we have reinvestigated the problem by expressing mutated Presenilins in a Presenilin-negative cell line. We confirm that Presenilins with mutated Asp residues are catalytically inactive. Unexpectedly, these mutated Presenilins are still partially processed into amino- and carboxyl-terminal fragments by a “Presenilinase”-like activity. They are also able to rescue Pen-2 expression and Nicastrin glycosylation in Presenilin-negative cells and become incorporated into large ∼440-kDa complexes as assessed by blue native gel electrophoresis. Our study demonstrates that the catalytic activity of Presenilin and its other functions in the generation, stabilization, and transport of the γ-secretase complex can be separated and extends the concept that Presenilins are multifunctional proteins.

Bing–Neel syndrome: an illustrative case and a comprehensive review of the published literature

Waldenstrom’s macroglobulinemia (WM) is a chronic lymphoproliferative disorder within the spectrum of lymphoplasmacytic lymphoma characterized by proliferation of plasma cells, small lymphocytes, and plasmacytoid lymphocytes. Central nervous system involvement is very rare (Bing–Neel [BN] syndrome). We present the case of a 62-year-old woman previously diagnosed with WM who presented with Bing–Neel syndrome and review the published literature which consists of only case reports. We performed a Medline search using the terms “Waldenstrom’s macroglobulinemia and central nervous system” and “Bing–Neel” collecting data on presentation, evaluation, treatment, and outcome and summarizing these findings in the largest pooled series to date. Central nervous system manifestations are localization related. Serum laboratory testing reflects systemic disease. Cerebrospinal fluid analysis may show lymphocytic pleocytosis, elevated protein, and IgM kappa or lambda light chain restriction; cytology results are variable. Imaging is frequently abnormal. Biopsy confirms the diagnosis. Treatment data are limited, but responses are seen with radiation and/or chemotherapy. BN syndrome is a very rare complication of WM that should be considered in patients with neurologic symptoms and a history of WM. Treatment should be initiated as responses do occur that may improve quality of life and extend it when limited or no active systemic disease is present.

Multiple brain abscesses due to Actinomyces species

We report a case of multiple brain abscesses due to Actinomyces species in a 35-year-old immunocompetent man who presented with a 2-month history of headache, diplopia, fever, and weight loss. Despite receipt of broad-spectrum antibiotics for over a month, he continued to have headaches and diplopia. He subsequently underwent right anterior temporal lobectomy and evacuation of abscesses. The diagnosis was aided by identification of sulfur granule on histopathological examination of cerebral cavitary lesion and Gram-positive filamentous rods seen on tissue-Gram stain.

Rupture of Cerebral Myxomatous Aneurysm Months After Resection of the Primary Cardiac Tumor

BackgroundThe natural history of cerebral aneurysms derived from metastatic spread of cardiac myxomas is not well known, and their management presents many dilemmas.MethodsCase report and literature review.ResultsAn 18-year-old man presented with an intraparenchymal hemorrhage several months after resection of an atrial myxoma. Angiography showed several myxomatous aneurysms, one of which had bled. The patient had a recurrent hemorrhage before undergoing surgical resection. MRI, angiographic, and pathological data are presented for this rare condition.ConclusionsMyxomatous aneurysms are important entities for neurointensivists to recognize and can present years after diagnosis. Patients presenting with cerebral infarction or hemorrhage of unknown etiology should undergo cardiac imaging to rule out atrial myxoma, as up to 50% of patients with myxomas present initially with stroke.

True aneurysm on the posterior meningeal artery associated with a dural arteriovenous fistula: Case report

BACKGROUNDWe report an unusual case of a true dural aneurysm arising from the posterior meningeal artery that fed a symptomatic dural arteriovenous fistula located at the right transverse-sigmoid sinus junction. CLINICAL PRESENTATIONA 29-year-old right-handed white woman presented with aneurysmal dilatation of hypertrophied posterior meningeal artery feeding a partially treated dural arteriovenous fistula. INTERVENTIONThe aneurysm, which measured approximately 3 mm in width and 5 mm in length, was located in the intracranial space with a thin-walled dome projecting toward the cerebellum. Its afferent and efferent vessels were identified, secured, and the lesion was excised en bloc. CONCLUSIONA thorough evaluation of all diagnostic studies should be performed for patients with vascular malformations to help identify these or other unusual lesions that may aid in the risk stratification process and management plan.

Response of an adult patient with pineoblastoma to vorinostat and retinoic acid.

We report the case of an adult patient with pineoblastoma (PBL) who had a complete radiographic response following treatment with vorinostat and retinoic acid. This regimen was used to treat bulky residual tumor that persisted despite radiation therapy (RT) and two cycles of cytotoxic chemotherapy. Vorinostat and retinoic acid were chosen as an alternative to cytotoxic chemotherapy, which our patient was unable to tolerate, based on preclinical data suggesting efficacy of this combination. MRI demonstrated a complete response to this regimen, which continues to remain stable without evidence of recurrence.

High-grade dural arteriovenous fistula simulating a bilateral thalamic neoplasm

Dural arteriovenous fistulae (dAVF) provide a diagnostic challenge and must be part of a broad differential in pursuit of a difficult diagnosis or unusual presentation. This case report demonstrates an initially misguided diagnosis of bilateral thalamic neoplasm and demonstrates the importance of continued pursuit until the correct diagnosis is obtained. Moreover, to our knowledge, this is the first reported case of a dAVF simulating a bilateral thalamic neoplasm. We present a patient with a provisional diagnosis of bilateral thalamic neoplasm based on clinical history and an advanced imaging workup including MR spectroscopy. Subsequent biopsy suggested venous congestion, hypoxia, and edema without neoplasia. Routine post-operative CT the following day revealed suggestion of dAVF due to the presence of residual contrast from prior unrelated abdominal CT. Cerebral angiography eventually revealed a Cognard grade IIb dAVF. Trans-arterial Onyx embolization resulted in a dramatic clinical and radiographic improvement. This case highlights an unusual presentation and challenging diagnosis of a dAVF and the importance of pursuing the correct diagnosis.

Cytology Features of Bing-Neel Syndrome

nique to clarify the case, using the valuable diagnostic material still present in the vial. Figure 2 shows a tissue fragment in the original Papanicolaou-stained thin-layer slide with nuclear blurring in the central part of the minibiopsy sample. The peripheral nuclei are clearly abnormal and display nucleolar prominence, highly suggestive for their malignant nature. In short, in our opinion this is a truly false negative ThinPrep in which the diagnostic cancerous epithelial fragments were overlooked in the original screening process.