Neurinoma of the oculomotor nerve--case report.
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Only 10 cases of oculomotor nerve neurinoma have been reported previously. The authors report the rarity of a neurinoma originating from Schwann cells of the oculomotor nerve. The diagnosis was based on the initial sign of oculomotor nerve paresis without involvement of other cranial nerves, neuroradiological and surgical findings, and histological features of the specimen obtained at surgery. (+info)
The adult form of Niemann-Pick disease type C.
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Niemann-Pick disease type C (NPC) is a fatal neurovisceral lipid storage disease of autosomal inheritance resulting from mutations in either the NPC1 (95% of families) or NPC2 gene. The encoded proteins appear to be involved in lysosomal/late endosomal transport of cholesterol, glycolipids and other molecules but their exact function is still unknown. The clinical spectrum of the disease ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. Based upon a comprehensive study of 13 unrelated adult patients diagnosed in France over the past 20 years as well as the analysis of the 55 other cases published since 1969, we have attempted to delineate the major clinical, radiological, biochemical and genotypic characteristics of adult NPC. Overall, mean age at onset (+/-SD) of neuropsychiatric symptoms was 25 +/- 9.7 years. The diagnosis of NPC was established after a mean delay of 6.2 +/- 6.4 years and the mean age at death (calculated from 20 cases) was 38 +/- 10.2 years. Major clinical features included cerebellar ataxia (76%), vertical supranuclear ophthalmoplegia (VSO, 75%), dysarthria, (63%), cognitive troubles (61%), movement disorders (58%), splenomegaly (54%), psychiatric disorders (45%) and dysphagia (37%). Less frequent signs were epilepsy and cataplexy. During the course of the disease, clinical features could be subdivided into (i) visceral signs (hepatomegaly or splenomegaly), (ii) cortical signs (psychiatric cognitive disorders and epilepsy); and (iii) deep brain signs (VSO, ataxia, movement disorders, dysarthria, dysphagia, cataplexy) which exhibited different evolution patterns. Asymptomatic and non-evolutive visceral signs were often noticed since early childhood (38.5% of our patients), followed by mild cortical signs in childhood (learning difficulties) and early adulthood (62% of cases among which 38% were psychiatric disorders). Deep brain signs were observed in 96% of patients and were usually responsible for death. In general, there was a good correlation between clinical signs and the localization of brain atrophy on MRI. The 'variant' biochemical phenotype characterized by mild abnormalities of the cellular trafficking of endocytosed cholesterol was over-represented in the adult form of NPC and seemed associated with less frequent splenomegaly in childhood and lesser psychiatric signs. Involvement of the NPC1 gene was shown in 33 families and of the NPC2 gene in one. Improving the knowledge of the disease among psychiatrists and neurologists appears essential since emerging treatments should be more efficient at the visceral or cognitive/psychiatric stages of the disease, before the occurrence of widespread deep brain neurological lesions. (+info)
T-cell lymphoma presenting as painful ophthalmoplegia.
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PURPOSE: To present a case of peripheral T-cell lymphoma presenting as painful ophthalmoplegia. METHODS: A 61-year-old woman presented with a 2-week history of headache and eyeball pain. Examination showed mild exophthalmos, complete ophthalmoplegia, and ptosis of the left eye. Under the impression of nonspecific orbital inflammation, she was treated with oral prednisone with initial response. Two months later, she revisited the clinic with exacerbated symptoms. Anterior orbitotomy and incisional biopsy was performed for the inferior rectus muscle lesion. RESULTS: Histopathologic examination revealed an infiltrate of atypical lymphoid cells between degenerative muscle bundles. It was consistent with peripheral T-cell lymphoma. A metastatic workup was performed without any evidence of extraorbital tumor. The patient was recommended to be treated with chemotherapy, however, refused to take the treatment. The patient died of progression of the disease in a month. CONCLUSIONS: T-cell lymphoma in the orbit can present as painful ophthalmoplegia and take a rapid clinical course. The disease should be regarded as one of the differential diagnosis for painful ophthalmoplegia refractory to corticosteroid therapy. (+info)
Mutations in mitochondrial tRNA genes: a frequent cause of neuromuscular diseases.
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We have sequenced the tRNA genes of mtDNA from patients with chronic progressive external ophthalmoplegia (CPEO) without detectable mtDNA deletions. Four point mutations were identified, located within highly conserved regions of mitochondrial tRNA genes, namely tRNA(Leu)(UAG), tRNA(Ser)(GCU), tRNA(Gly) and tRNA(Lys). One of these mutations (tRNA(Leu)(UAG)) was found in four patients with different forms of mitochondrial myopathy. An accumulation of three different tRNA point mutations (tRNA(Leu)(UAG)), tRNA(Ser)(GCU) and tRNA(Gly) was observed in a single patient, suggesting that mitochondrial tRNA genes represent hotspots for point mutations causing neuromuscular diseases. (+info)
High-resolution magnetic resonance imaging of the extraocular muscles and nerves demonstrates various etiologies of third nerve palsy.
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PURPOSE: The etiology of third nerve palsy is usually diagnosed by history, motility examination, and presence of lid and pupil involvement, as well as cranial and vascular imaging. We used high-resolution magnetic resonance imaging (hrMRI) of the oculomotor nerve and affected extraocular muscles (EOMs) to investigate oculomotor palsy. DESIGN: Prospective, noncomparative, observational case series in an academic referral setting. METHODS: Twelve patients with nonaneurysmal oculomotor palsy of 0.75 to 252 months' duration were studied. In the orbit and along the intracranial oculomotor nerve, hrMRI at 1- to 2-mm thickness was performed. Coronal plane images of each orbit were obtained in multiple, controlled gaze positions. Structural abnormalities of the oculomotor nerve and associated changes in EOM volume and contractility were evaluated. RESULTS: Cases were categorized as tumor related, congenital, diabetic, traumatic, and idiopathic according to clinical characteristics and hrMRI findings. Reduction of volume and contractility of affected EOMs were noted in six patients; however, there was no marked EOMs atrophy in two cases of diabetic oculomotor palsy, and there were four cases of aberrant regeneration. hrMRI demonstrated the oculomotor nerve at the midbrain and at EOMs in all cases, and in two cases with previous normal neuroimaging elsewhere that demonstrated contrast-enhancing tumors on the oculomotor nerve. One patient with apparently unilateral congenital inferior division oculomotor palsy had no detectable ipsilateral and a hypoplastic contralateral oculomotor nerve exiting the midbrain. CONCLUSIONS: hrMRI provides valuable information in patients with oculomotor palsy, such as structural abnormalities of the orbit and oculomotor nerve, and atrophy and diminished contractility of innervated EOMs. This information could be helpful in diagnosis and management of oculomotor palsy. (+info)
Introduction of disease-related mitochondrial DNA deletions into HeLa cells lacking mitochondrial DNA results in mitochondrial dysfunction.
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Mutant mitochondrial DNA with large-scale deletions (delta-mtDNA) has been frequently observed in patients with chronic progressive external ophthalmoplegia (CPEO), a subgroup of the mitochondrial encephalomyopathies. To exclude involvement of the nuclear genome in expression of the mitochondrial dysfunction characteristic of CPEO, we introduced the mtDNA of a CPEO patient into clonal mtDNA-less HeLa cells and isolated cybrid clones. Quantitation of delta-mtDNA in the cybrids revealed that delta-mtDNA was selectively propagated with higher levels of delta-mtDNA correlating with slower cellular growth rate. In these cybrid clones, translational complementation of the missing tRNAs occurred only when delta-mtDNA was less than 60% of the total mtDNA, whereas accumulation of delta-mtDNA to greater than 60% resulted in progressive inhibition of overall mitochondrial translation as well as reduction of cytochrome c oxidase activity throughout the organelle population. Because these cybrids shared the same nuclear background as HeLa cells, these results suggest that large-scale deletion mutations of mtDNA alone are sufficient for the mitochondrial dysfunction characteristic of CPEO. (+info)
Nidal embolization of brain arteriovenous malformations using Onyx in 94 patients.
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BACKGROUND AND PURPOSE: To report our experience in the treatment of brain arteriovenous malformations (BAVMs) using Onyx (ev3, Irvine, Calif). PATIENTS AND METHODS: From January 1999 to October 2004, 94 patients with BAVMs were treated endovascularly in our department. They were 51 (54%) men and 43 (46%) women with a mean age of 32 years. A total of 210 endovascular procedures were performed with Onyx as the sole embolic agent in 88 procedures; Onyx and n-butyl cyanoacrylate (n-BCA) were used in combination in 50 procedures, and n-BCA alone was used in 72 procedures. RESULTS: The course of endovascular treatment was completed in 53 patients. In 26 patients (49%, 26/53) an angiographic cure was achieved using embolization as the sole therapeutic technique. Seven (13%, 7/53) patients underwent a surgical resection of the residual BAVM nidus, 20 (38%, 20/53) patients underwent radiosurgical treatment after nidal size reduction <2 cm was accomplished by endovascular treatment. Further endovascular treatment was planned in 33 patients, whereas in 5 patients, the continuation of embolization was aborted due to difficult nidus catheterization. Procedure-related permanent neurologic deficits were observed in 8 (8.5%, 8/94) patients. There were 3 procedure-related deaths. CONCLUSION: Onyx is suitable for brain BAVM embolizations and allows obtaining higher rates of anatomic cures compared with those obtained previously with other embolic agents. (+info)
Maintaining precursor pools for mitochondrial DNA replication.
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Among the human diseases that result from abnormalities in mitochondrial genome stability or maintenance are several that result from mutations affecting enzymes of deoxyribonucleoside triphosphate (dNTP) metabolism. In addition, it is evident that the toxicity of antiviral nucleoside analogs is determined in part by the extent to which their intracellular conversion to dNTP analogs occurs within the mitochondrion. Finally, recent work from this laboratory has shown considerable variation among different mammalian tissues with respect to mitochondrial dNTP pool sizes and has suggested that natural asymmetries in mitochondrial dNTP concentrations may contribute to the high rates at which the mitochondrial genome undergoes mutation. These factors suggest that much more information is needed about maintenance and regulation of dNTP pools within mammalian mitochondria. This review summarizes our current understanding and suggests directions for future research. (+info)