Impairment of intermediate somatosensory function in corticobasal syndrome.

Corticobasal syndrome (CBS) is characterized by unilateral atrophy of the brain. New diagnostic criteria for CBS include intermediate somatosensory dysfunction. Here, we aimed to carefully examine intermediate somatosensory function to identify tests which can assess impairment in CBS patients. Using voxel-based morphometry (VBM), we also aimed to show the anatomical bases of these impairments. Subjects included 14 patients diagnosed with CBS and 14 patients with Parkinson's disease (PD). Patients were evaluated using intermediate somatosensory tests and neuropsychological assessments. VBM was used to analyze differences in gray matter volumes between CBS and PD patients. In the PD group, no tests showed a significant difference between the dominant-side onset and the non-dominant-side onset. In the CBS group, all tests showed worse scores on the affected side. For detecting intermediate somatosensory dysfunction in CBS, two tests are recommended: tactile object naming and 2-point discrimination. VBM analysis showed that the volume of the left post- and pre-central gyrus, and both sides of the supplementary motor area were significantly decreased in the CBS group compared to the PD group. Although CBS remains untreatable, early and correct diagnosis is possible by performing close examination of intermediate somatosensory function.

Vertebral artery dissection associated with familial Mediterranean fever and Behçet's disease.

Vertebral artery dissection and recurrent meningitis are rare complications in Behçet's disease. Behçet's disease may be associated with familial Mediterranean fever. Here, we describe a 52-year-old woman with severe headache who exhibited recurrent meningitis and vertebral artery dissection. Cerebrospinal fluid showed high levels of interleukin-6. Magnetic resonance imaging revealed right vertebral artery dissection. The patient had three heterozygous mutations in the familial Mediterranean fever gene (MEFV) gene. She fulfilled criteria for diagnosis of Behçet's disease and familial Mediterranean fever. In conclusion, mutations of the MEFV gene may cause neuro-inflammatory disorders and cerebrovascular disorders by reducing anti-inflammatory activity of pyrin.

Diffusion tensor imaging and magnetic resonance spectroscopy in a patient with adult onset tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) 1 or TSC2 is mutated in most TSC patients. TSC2 mutations are more frequently associated with worse outcomes, earlier age at seizure onset, more severe intellectual disability, and higher tuber load than TSC1. The degree of white matter involvement is thought to be associated with the severity of neurological impairment. At present, genotype-phenotype correlations and relationship between tuber burden and neurological disability in TSC are debatable. We presented a 43-year-old patient with TSC2 mutation, whose symptom was only incomplete quadrantic visual field deficit in spite of multiple brain tubers. The visual field deficit was thought to be due to a small lesion in the upper medial part of the optic radiation revealed by diffusion tensor imaging. Her brain tubers showed normal findings in magnetic resonance spectroscopy. Our case suggested that neurological and neuropsychiatric manifestations of TSC are affected by the quality rather than number of the lesions. In addition, MRS may be useful to identify the correlation between brain tubers and neurological disability in TSC patients.

Double-seropositive myasthenia gravis with acetylcholine receptor and low-density lipoprotein receptor-related protein 4 antibodies associated with invasive thymoma.

We describe two cases of myasthenia gravis (MG) with double seropositivity for acetylcholine receptor (AChR) and low-density lipoprotein receptor-related protein 4 (LRP4) antibodies (AChR/LRP4-MG) with invasive thymoma. Both cases showed myasthenic weakness, which was restricted to the ocular muscles for >5 months from onset, and then unprovoked severe clinical deterioration supervened with predominant bulbar symptoms. The patients responded adequately to therapeutic intervention. Serum AChR antibody levels at post-intervention were markedly decreased, whereas LRP4 antibodies were almost unchanged in case 1 and slightly decreased in case 2. Although our results suggest that patients with AChR/LRP4-MG are likely to present with more severe symptoms than those with LRP4-MG, none of the previously reported cases had thymomas. Coexistence of autoantibodies may reflect breakdown of self-tolerance caused by invasive thymomas. The main cause affecting symptoms of MG in our cases was probably AChR antibodies, and anti-LRP4 antibodies might have been an exacerbating factor.

Neuropsychological Features of Microbleeds and Cortical Microinfarct Detected by High Resolution Magnetic Resonance Imaging.

BACKGROUND: Lobar microbleeds (MBs) and cortical microinfarct (CMI) are caused by cerebral amyloid angiopathy in the elderly and increase in number in Alzheimer's disease. OBJECTIVE: The aim of this study is to elucidate the effects of lobar MBs and CMIs on cognitive function. METHODS: The subjects were outpatients who visited the memory clinic of Mie University Hospital. Among 120 subjects, 109 patients fulfilled the inclusion criteria. We quantitatively estimated MBs and CMIs using double inversion recovery and 3D FLAIR images of 3T MRI. Neuropsychological assessments included intellectual, memory, constructional, and frontal lobe function. RESULTS: Of the 109 patients, MBs and CMIs were observed in 68 (62%) and 17 (16%) subjects, respectively. Of the 68 patients with MBs, lobar MBs were found in 28, deep MBs in 8 and mixed MBs in 31. In each age group, the number of MBs increased in patients with CMI (CMI+ group) than those without CMI (CMI- group), and MBs and CMIs additively decreased MMSE scores. In psychological screens, the MBs+ group with more than 10 MBs showed significantly lower scores of category- and letter-WF than MB- group. The CMI+ group showed significantly worse scores than CMI- group in Japanese Raven's coloured progressive matrices, Trail Making Test-A, category- and letter-word fluency and copy and drawing of figures. CONCLUSION: Lobar MBs and CMIs in the elderly frequently coexisted with each other and additively contributed to cognitive impairment, which is mainly predisposed to frontal lobe function.

Statins and myotoxic effects associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies: an observational study in Japan.

Statins have a variety of myotoxic effects and can trigger the development of inflammatory myopathies or myasthenia gravis (MG) mediated by immunomodulatory properties. Autoantibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) have been identified in patients with statin-associated myopathy. The purpose of the present study is to develop an enzyme-linked immunosorbent assay (ELISA) of anti-HMGCR antibodies and to elucidate the clinical significance of anti-HMGCR antibodies in Japanese patients with inflammatory myopathies or MG. We enrolled 75 patients with inflammatory myopathies, who were all negative for anti-signal recognition particle and anti-aminoacyl transfer RNA synthetase antibodies. They were referred to Keio University and National Center of Neurology and Psychiatry between October 2010 and September 2012. We also studied 251 patients with MG who were followed at the MG Clinic at Keio University Hospital. Anti-HMGCR antibodies were detected by ELISA. We investigated demographic, clinical, radiological, and histological findings associated with anti-HMGCR antibodies. We established the anti-HMGCR ELISA with the recombinant protein. Protein immunoprecipitation detected autoantigens corresponding to HMGCR. Immunohistochemistry using muscle biopsy specimens revealed regenerating muscle fibers clearly stained by polyclonal anti-HMGCR antibodies and patients' serum. Anti-HMGCR autoantibodies were specifically detected in 8 patients with necrotizing myopathy. The seropositivity rate in the necrotizing myopathy patients was significantly higher than those in the patients with other histological diagnoses of inflammatory myopathies (31% vs 2%, P = 0.001). Statins were administered in only 3 of the 8 anti-HMGCR-positive patients. Myopathy associated with anti-HMGCR antibodies showed mild limb weakness and favorable response to immunotherapy. All 8 patients exhibited increased signal intensities on short T1 inversion recovery of muscle MRI. Of the 251 patients with MG, 23 were administered statins at the onset of MG. One late-onset MG patient experienced MG worsening after 4-wk treatment with atorvastatin. However, anti-HMGCR antibodies were not detected in the 251 MG patients except for one early-onset MG patient with no history of statin therapy. Anti-HMGCR antibodies are a relevant clinical marker of necrotizing myopathy with or without statin exposure, but they are not associated with the onset or deterioration of MG.

[Diffusion-weighted MR imaging of meningeal involvement in Wegener's granulomatosis].

We report a 65-year-old female with meningeal involvement in Wegener's granulomatosis (WG). At 52 years of age, she was diagnosed as having WG by lung biopsy and elevated proteinase3 anti-neutrophil cytoplasmic antibody titer. She had been maintained on prednisolone. Three weeks before admission, she developed deterioration of mental status. On examination, neurological abnormalities included right hemiparesis, confusion, memory loss, psychomotor slowing and agraphia. CSF was normal. Diffusion-weighted images (DWI) showed high intensity lesions in the subarachnoid space over the left hemisphere. Fluid attenuated inversion recovery (FLAIR) images showed high intensity signal in the subarachnoid space with mild swelling of the cortex and abnormal meningeal enhancement corresponding to the high intensity area on DWI. She was treated with intravenous administration of methylprednisolone (1,000 mg/day for 3 days) and cyclophosphamide, and gradually improved in symptoms and abnormal hyperintensity on DWI. Involvement of the meninges in WG is rare. The dura mater is involved more frequently than the pia mater. Pathological findings of the meninges in WG has been reported to be granulomatous inflammation. Restricted diffusion in the subarachnoid space has been described to occur in a viscous mixture of proteins and inflammatory cells, similarly to the DWI hyperintensity in pyogenic abscesses. In our case, abnormal hyperintensity on DWI was interpreted as a dense inflammatory infiltrate in the leptomeninges. Therefore, DWI and FLAIR image have been shown to be useful for demonstration of leptomeningeal lesions in WG.

Clinical features and underlying causes of cerebral venous thrombosis in Japanese patients.

The clinical symptoms, causative factors, and prognosis in Japanese patients with cerebral venous thrombosis have not been adequately characterized. The present study describes these features in patients in Japan. Twenty-two patients with cerebral venous thrombosis were retrospectively identified. Diagnosis was confirmed by either digital subtraction angiography, magnetic resonance venography, or contrast-enhanced computed tomography. Demographic data and clinical and radiological features were recorded and analyzed for each patient. Prognosis was evaluated by the modified Rankin scale (mRS) at the time of hospital discharge. The most frequent symptom of cerebral venous thrombosis was headache (59.1 %). Causative factors included congenital thrombophilia (31.8 %), acquired thrombophilia (27.3 %), and iron-deficiency anemia (13.6 %). Of seven patients with congenital thrombophilia, four had mutations in the protein S gene, two had mutations in the protein C gene, and one had mutations in the antithrombin gene. All patients were alive at discharge from hospital. Nineteen of the 22 patients (86.4 %) recovered completely or exhibited only mild residual symptoms (mRS 0-2). However, three patients (13.6 %) had a poor prognosis (mRS 3-5). Cerebral venous thrombosis in Japanese patients is frequently associated with congenital thrombophilia and protein S gene mutation.

Global aphasia without hemiparesis: the underlying mechanism examined by transcranial magnetic stimulation.

INTRODUCTION: Global aphasia without hemiparesis (GAWH) is a rare stroke syndrome. Using transcranial magnetic stimulation (TMS), we evaluated 2 possible pathogenic mechanisms for GAWH: sparing of the decussated pyramidal tract, or alternatively, compensation by the ipsilateral pyramidal tract. METHODS: Six patients were diagnosed to have GAWH by the Standard Language Test of Aphasia for Japanese. All patients underwent brain magnetic resonance (MR) imaging and angiography. According to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, stroke subtype was determined as 3 patients with cardioembolic stroke, 2 with large-artery atherosclerosis, and 1 with another type. All patients underwent TMS, using a figure-of-8 coil, from 3 to 12 months after the onset, and motor evoked potentials were recorded on the abductor digiti minimi muscles. RESULTS: All patients had left-sided frontal or temporal lesions that were confirmed by MR diagnostic imaging. No motor evoked potential could be recorded by ipsilateral TMS. In 3 patients, brain stimulation on either side evoked the same amplitude on the contralateral abductor digiti minimi, whereas in the other 3 patients, the amplitude was suppressed on the right side. The infarction in the former patients was caused by cardioembolism and in the latter was not. In serial slices of brain MR imaging, the pyramidal tract was spared in the former and was involved to various degrees in the latter 3 patients. CONCLUSIONS: We recommend that GAWH was caused by the sparing of the decussated pyramidal tract. The pyramidal tract was intact in cases of GAWH caused by cardioembolism and subclinically impaired by other causes.

[Case of ipsilateral monoparesis by lacunar infarction: a consideration on the pathological mechanism].

An 81-year-old man had sudden-onset dysarthria and weakness in the right leg, and was admitted to our hospital in July 2009. Neurological examination showed right leg monoparesis, sensory disturbance on the right limbs, dysarthria, and decreased deep tendon reflexes. Brain MRI revealed an acute lacunar infarction in the right corona radiata and an old lacunar infarction in the left centrum semiovale, which occurred 4 years before. MR tractography disclosed impaired motor fibers in the right corona radiata, and transcranial magnetic stimulation (TMS) suggested diminished innervation from the bilateral cerebral cortices to the right leg. These results collectively indicated that reorganization of the pyramidal fibers were responsible for the monoparesis ipsilateral to the lacunar infarction, although anomalous pyramidal fibers with ipsilateral innervation were responsible for ipsilateral hemiplegia a previous study.