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We herein report a case of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A 24-year-old woman developed unilateral optic neuritis 3 weeks after contracting coronavirus disease 2019 (COVID-19), followed by intracranial demyelinating lesions and myelitis. Since serum anti-MOG antibody was positive, we diagnosed MOG antibody-associated disease. Immunotherapy with steroids resulted in the rapid improvement of neurological symptoms. This is a suggestive case, as there are no reports of MOG antibody-associated disease with multiple neurological lesions occurring after COVID-19. The response to immunotherapy was favorable. This case suggests that it is important to measure anti-MOG antibodies in patients who develop inflammatory neurological disease after COVID-19.

Background and aims We explored the association between the total small vessel disease score obtained from baseline magnetic resonance imaging and subsequent cerebro-cardiovascular events in neurologically healthy Japanese adults. Methods The presence of small vessel disease features, including lacunae, cerebral microbleeds, white matter changes, and basal ganglia perivascular spaces on magnetic resonance imaging, was summed to obtain a “total small vessel disease score” (range, 0–4). After excluding participants with previous stroke or ischemic heart disease, intracranial artery stenosis (≥50%), or cerebral aneurysm (≥4 mm), a total of 1349 participants (mean age, 57.7 years; range, 22.8–85.0 years; 46.9% male) were classified into three groups by total small vessel disease score: 0 ( n = 984), 1 ( n = 269), and ≥2 ( n = 96). Cerebro-cardiovascular events (i.e., any stroke, transient ischemic attack, ischemic heart disease, acute heart failure, and aortic dissection) were defined as the primary end point. The hazard ratio (HR) of events during follow-up was calculated using Cox proportional hazards modeling with adjustments for age, sex, hypertension, diabetes mellitus, and smoking. Cumulative event-free rates were estimated using the Kaplan–Meier method. Results During follow-up (mean, 6.7 years), 35 cerebro-cardiovascular (16 cerebrovascular) events were identified. Higher small vessel disease score was associated with increased risk of cerebro-cardiovascular events (HR per unit increase, 2.17; 95% confidence interval, 1.36–3.46; P = 0.001). Events were more frequent among participants with higher score ( P Conclusions This study offered additional evidence for the clinical relevance of total small vessel disease score, suggesting the score as a promising tool to predict the risk of subsequent vascular events even in healthy populations.

The total cerebral small vessel disease (SVD) score is a proposed comprehensive index of SVD severity in the brain. However, data on lifestyle-related risk factors affecting SVD scores are limited. We conducted a cross-sectional study with 858 neurologically healthy adults who underwent brain magnetic resonance imaging (MRI). Information on clinical and lifestyle-related risk factors was obtained from health screenings. The SVD score (0-4) was calculated from the presence of lacunes, cerebral microbleeds, moderate to severe white matter lesions, and basal ganglia perivascular spaces on MRI. Subjects were divided into two groups by SVD score; potential risk factors and their joint effects in the two groups were assessed by logistic regression. Biologic interactions were estimated using the synergy index. After adjustment for possible confounders, the adjusted odds ratio for moderate to severe SVD scores (SVD score ≥ 2) was 1.12 (95% confidence interval (CI) 1.08-1.16) for age per year, 1.33 (95% CI 1.02-1.74) for body mass index per standard deviation, 3.39 (95% CI 1.90-6.03) for hypertension, 2.31 (95% CI 1.14-4.69) for diabetes, and 2.35 (95% CI 1.10-5.02) for smoking. Hypertension and current smoking had a synergistic effect on the risk of moderate to severe SVD (OR 10.59, 95% CI 3.97-28.3; synergy index 4.03, 95% CI 1.17-28.30), and the combination of hypertension and diabetes had an additive effect on the risk of moderate to severe SVD (OR 9.48, 95% CI 3.80-23.66; synergy index 2.12, 95% CI 0.68-6.67). Therefore, combined strategies for managing hypertension, smoking, and diabetes may be effective for preventing SVD.

Introduction Perry disease (Perry syndrome), a hereditary TAR DNA-binding protein 43 (TDP-43) proteinopathy, is caused by dynactin subunit 1 (DCNT1) mutations and is characterized by rapidly progressive parkinsonism accompanied by depression, apathy, unexpected weight loss, and respiratory symptoms including central hypoventilation and central sleep apnea. Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is considered a diagnostic biomarker for Lewy body disease (LBD), as denervation of cardiac sympathetic nerves is a pathological feature in LBD. However, our previous studies have reported a decreased cardiac uptake of MIBG in patients with Perry disease. In this study, we aimed to correlate the MIBG myocardial scintigraphy findings with clinical features in Perry disease. Methods We evaluated data obtained from a multicenter survey of patients of Japanese origin with suspected Perry disease, who visited neurology departments in Japan from January 2010 to December 2018. We screened each patient's DNA for the DCTN1 mutation using Sanger sequencing and obtained the clinical details of all patients including findings from their MIBG myocardial scintigraphy. Results We identified two novel mutations, p.G71V and p.K68E, in DCTN1 in patients from two different families. The majority of patients (7/8, 87.5%) showed a decrease in cardiac uptake (heart to mediastinum ratio) in MIBG myocardial scintigraphy. These patients commonly presented with symptoms related to autonomic dysfunction: constipation, fecal incontinence, urinary disturbance, and orthostatic hypotension. Conclusions MIBG myocardial scintigraphy may be a useful biomarker of autonomic dysfunction in Perry disease.

Objective We explored the association between the total small vessel disease (SVD) score obtained with magnetic resonance imaging and risk factors and outcomes in the Japanese population. Methods The presence of SVD features, including lacunes, cerebral microbleeds, white matter changes, and basal ganglia perivascular spaces on MRI, was summed to obtain a “total SVD score” (range 0-4). Ordinal and multinomial logistic regression analyses were performed to investigate the association of higher total SVD scores with vascular risk factors, the Mini-Mental State Examination (MMSE) score, and cerebral atrophy. Results We included 1,451 neurologically healthy adults (mean age, 57.1 years; 47% male). A multivariate ordinal logistic regression analysis showed that the total SVD score was associated with aging, hypertension, blood pressure (BP), diabetes mellitus, MMSE score, and deep cerebral atrophy, but the equal slopes assumption between scores did not hold. A multivariate multinomial logistic regression analysis (total SVD score 0=reference) showed that aging, hypertension, and BP were positively associated with scores of 1, 2, or ≥3. These effects, presented as odds ratios (ORs), increased as the score increased and were strongest with a score of ≥3 [aging (per 10-year increment), OR 4.00, 95% confidence interval (CI) 2.47-6.46; hypertension, OR 5.68, 95% CI 2.52-12.80; systolic BP (per standard deviation increase), OR 1.96, 95% CI 1.41-2.74, respectively]. Diabetes mellitus and deep cerebral atrophy tended to be associated with the SVD scores. The MMSE score showed no consistent associations. Conclusion The total SVD score may be a promising tool for indexing SVD, even in the Japanese population.

A hemi-paralyzed 86-year-old man was diagnosed with ischemic stroke and underwent thrombolysis. Pre-thrombolysis brain magnetic resonance imaging revealed extensive strictly lobar cerebral microbleeding (CMB). Post-thrombolytic computed tomography revealed asymptomatic multiple intracerebral hemorrhaging (ICH). His age, CMB topography, and decreased cerebral spinal fluid amyloid-β 40 and 42 levels were compatible with a diagnosis of cerebral amyloid angiopathy (CAA). There is no consensus on the safety of thrombolysis for acute stroke patients with CAA. Patients with CAA might have a higher incidence of thrombolysis-related ICH than those without CAA.

We herein report the case of a 38-year-old man who developed parkinsonism 4 years after ingesting glyphosate. The patient presented with right-sided bradykinesia and cogwheel rigidity without autonomic symptoms. Magnetic resonance imaging of the brain and [123I]-metaiodobenzylguanidine myocardial scintigraphy were normal. A drastic response to levodopa and the presence of levodopa-induced dyskinesia without strong non-motor symptoms were seen in this patient. We considered that young-onset atypical parkinsonism was associated with a history of sublethal glyphosate ingestion. Epidemiologic investigations have shown that exposure to pesticides is a risk factor for Parkinson's disease (PD). Our findings support the notion that glyphosate exposure might be related to the onset of PD.

Objective To characterize the genetic and clinical features of patients with autosomal dominant adult-onset demyelinating leukodystrophy (ADLD) carrying duplication and deletion upstream of lamin B1 (LMNB1). Methods Ninety-three patients with adult-onset leukoencephalopathy of unknown etiology were genetically analyzed for copy numbers of LMNB1 and its upstream genes. We examined LMNB1 expression by reverse transcription-qPCR using total RNA extracted from peripheral leukocytes. Clinical and MRI features of the patients with ADLD were retrospectively analyzed. Results We identified 4 patients from 3 families with LMNB1 duplication. The duplicated genomic regions were different from those previously reported. The mRNA expression level of LMNB1 in patients with duplication was significantly increased. The clinical features of our patients with LMNB1 duplication were similar to those reported previously, except for the high frequency of cognitive impairment in our patients. We found 2 patients from 1 family carrying a 249-kb genomic deletion upstream of LMNB1. Patients with the deletion exhibited relatively earlier onset, more prominent cognitive impairment, and fewer autonomic symptoms than patients with duplication. The presence of cerebellar symptoms and lesions may be characteristic in our patients with the deletion compared with the previously reported family with the deletion. Magnetic resonance images of patients with the deletion exhibited a widespread distribution of white matter lesions including the anterior temporal region. Conclusions We identified 4 Japanese families with ADLD carrying duplication or deletion upstream of LMNB1. There are differences in clinical and MRI features between the patients with the duplication and those with the deletion upstream of LMNB1.

Background: The clinical importance of ovarian teratoma in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been established, however investigations of ovarian teratoma in patients with anti-NMDAR encephalitis remain limited. Objective: To clarify differences in NMDAR distribution and lymphocyte infiltration in ovarian teratoma between patients with and without anti-NMDAR encephalitis. Methods: Participants initially comprised 26 patients with ovarian teratomas. NMDAR distribution and lymphocyte infiltration in ovarian teratomas were examined using immunopathological techniques. Clinical, laboratory, and radiological data were compared between patients showing the features of encephalitis. Anti-NMDAR antibodies in the serum and cerebrospinal fluid were also measured in encephalitis patients. Results: Neuronal tissues were obtained from ovarian teratomas in 22 patients (after excluding 4 patients who did not satisfy the inclusion criteria), and the presence of NMDA receptor subunits was revealed in all patients. Lymphocyte infiltration was more frequent in the encephalitis group (n = 3) than in the non-encephalitis group. In particular, dense B-lymphocyte infiltration near neural tissues was observed in the encephalitis group. Conclusions: Differences in lymphocyte infiltration in ovarian teratomas between anti-NMDAR encephalitis and non-encephalitis patients suggest the immunological importance of the ovarian teratoma as the site of antigen presentation in anti-NMDAR encephalitis.

It is unclear when and which neurologic deficits should be examined within 24 hours after intravenous recombinant tissue plasminogen activator (rt-PA) therapy for acute ischemic stroke. Relationships between serial changes in National Institutes of Health Stroke Scale (NIHSS) subscores and neurologic deterioration (ND) within the first 24 hours after therapy were investigated in 43 consecutive patients. The NIHSS score was measured by neurologists 28 times within 24 hours after therapy. Assessments of subscores associated with ND, defined as the first change 4 or more points from baseline, were performed at 15 minutes (most frequent time of the first ND), 120 minutes (median time of the first ND), and 24 hours after therapy. Seventeen of 43 patients (age range, 55-94 years) showed ND. Of the NIHSS subscores, increases in scores for loss of consciousness (15 minutes, P = .001; 120 minutes, P = .026; 24 hours, P = .018) and motor limbs total (15 minutes, P = .014; 120 minutes, P = .031) were related to deterioration. Items such as questions, gaze, visual fields, ataxia, language, dysarthria, and extinction/inattention were not related to deterioration at any time. In conclusion, ND of ischemic stroke patients treated with intravenous rt-PA therapy was frequently seen within 120 minutes after therapy. Items such as loss of consciousness and motor limbs total may be considered indices for monitoring neurologic deficits after therapy.

Background and Purpose— Brain microbleeds (MBs) are considered to be associated with cognitive decline and can be pathologically and topographically classified as cerebral amyloid angiopathy-related (located in lobar regions) and hypertensive microangiopathy-related (located in deep regions). We examined whether different effects on global cognitive function might be seen with different distributions of MBs. Methods— A total of 1279 adults without neurological disorders were studied prospectively. Subjects were divided into 4 groups: without-MBs group; lobar group; deep group; and with in both areas (diffuse group). The Mini-Mental State Examination was administered to determine global cognitive functions, with scores Results— MBs were detected in 98 subjects (8%): 36 subjects (3%) classified as lobar group, 48 subjects (4%) as deep group, and 14 subjects (1%) as diffuse group. Subnormal scores were found in 76 subjects (5.9%), associated with age, education, hypertension, severe white matter hyperintensities, and distribution and number of MBs. In the final model of logistic regression analysis, the deep group (OR, 2.79; 95% CI, 1.14–6.79) was associated with subnormal scores, whereas the lobar group (OR, 0.77; 95% CI, 0.17–3.44) was not. Trend for the diffuse group did not reach the level of significance (OR, 5.01; 95% CI, 0.88–28.41). These trends were also seen in analysis using another cut-off point for subnormal score. Scores for total Mini-Mental State Examination and attention and calculation were significantly lower in the deep group and the diffuse groups compared with the without-MBs group. Conclusions— This Japanese cross-sectional study demonstrated that MB-related global cognitive dysfunction seems to occur based on hypertensive pathogenesis rather than on cerebral amyloid angiopathy.

Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive disorder characterized by cerebellar ataxia, congenital cataracts, mental retardation, primary hypogonadism, skeletal abnormalities and myopathy, and patients with MSS are considered to be at risk of falls and bone fractures. We report a patient with MSS who received testosterone replacement therapy and risedronate administration. Muscle strength and the MRI features of the skeletal muscles were not changed, but low bone mass was improved by these treatments, and improvement has continued after risedronate treatment alone. This case suggests that treatment of MSS-related low bone mass using bisphosphonates is likely beneficial.

ObjectiveTo characterize the genetic and clinical features of patients with autosomal dominant adult-onset demyelinating leukodystrophy (ADLD) carrying duplication and deletion upstream of lamin B1 (LMNB1).MethodsNinety-three patients with adult-onset leukoencephalopathy of unknown etiology were genetically analyzed for copy numbers of LMNB1 and its upstream genes. We examined LMNB1 expression by reverse transcription-qPCR using total RNA extracted from peripheral leukocytes. Clinical and MRI features of the patients with ADLD were retrospectively analyzed.ResultsWe identified 4 patients from 3 families with LMNB1 duplication. The duplicated genomic regions were different from those previously reported. The mRNA expression level of LMNB1 in patients with duplication was significantly increased. The clinical features of our patients with LMNB1 duplication were similar to those reported previously, except for the high frequency of cognitive impairment in our patients. We found 2 patients from 1 family carrying a 249-kb genomic deletion upstream of LMNB1. Patients with the deletion exhibited relatively earlier onset, more prominent cognitive impairment, and fewer autonomic symptoms than patients with duplication. The presence of cerebellar symptoms and lesions may be characteristic in our patients with the deletion compared with the previously reported family with the deletion. Magnetic resonance images of patients with the deletion exhibited a widespread distribution of white matter lesions including the anterior temporal region.ConclusionsWe identified 4 Japanese families with ADLD carrying duplication or deletion upstream of LMNB1. There are differences in clinical and MRI features between the patients with the duplication and those with the deletion upstream of LMNB1.

Background and Purpose— Increasing attention has been paid to associations between cognitive dysfunction and brain microbleeds (MBs). Because all previous studies have investigated patients with neurological disorders, we examined subjects without neurological disorder in order to clarify pathogenic relationships. Methods— A total of 518 consecutive adults without neurological disorder who had undergone health-screening tests of the brain were studied prospectively. Gradient-echo T2*-weighted MRI using a 1.5-T system was used to detect MBs. The Mini-Mental State Examination (MMSE) was administered to determine cognitive functions. MMSE scores 1.5 SDs below the age-related mean were regarded as subnormal. Results— MBs were found in 35 subjects (6.8%). MMSE score 1.5 SDs below the age-related mean in 34 subjects (6.6%). Univariate analysis showed presence and number of MBs, short duration of education, and severe white matter hyperintensities as significantly associated with subnormal scores. In logistic regression analysis, presence of MBs (odds ratio [OR], 5.44; 95% CI, 1.83 to 16.19) and number of MBs (OR, 1.32; 95% CI, 1.04 to 1.68) still displayed significant associations with MMSE score 1.5 SDs below the age-related mean. Among MMSE subscores, “attention and calculation” was significantly lower in MB-positive subjects ( P =0.017). Conclusions— MBs appear to be primarily associated with global cognitive dysfunction.

Marinesco-Sjögren syndrome (MSS) is an autosomal recessive multisystem disorder characterized by cerebellar ataxia, cataracts, progressive muscular weakness, and developmental and mental retardation. Recently, mutations in the SIL1 gene on chromosome 5q31 have been shown to be a cause of MSS. We sequenced the entire SIL1-coding region in 3 unrelated Japanese patients with classical MSS and identified a novel homozygous frameshift insertion mutation, 936_937insG, in exon 9 in all 3 patients.

Objective To clarify the incidence and clinical significance of HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) showing T2 hyperintensity in the spinal cord on magnetic resonance images (MRI). Patients and Methods We reviewed the spinal cord MRI of 38 HAM/TSP patients and analyzed them in relation to clinical and laboratory findings. Analyzed data were: age at onset, disease duration, disability status, responsiveness to interferon therapy, brain abnormalities on MRI, serum anti-HTLV-I titers, and cerebrospinal fluid (CSF) findings. Results MRI findings of the spinal cord were classified into 3 types, "normal" (n=22, 57.9%), "atrophy" (n=13, 34.2%) and "T2-hyperintensity" (n=3, 7.9%). Patients in the normal and atrophy types showed slowly progressive paraparesis. Significant differences were not found between the normal and atrophy types in any clinical or laboratory data, including disease duration, disability status and responsiveness to interferon-alpha therapy. Meanwhile, all patients showing T2-hyperintensity had severe paraparesis of a rapid progressive nature, with CSF IgG elevation. Conclusion HAM/TSP with T2-hyperintensity on spinal MRI shows a rapid progressive clinical course with severe motor impairment. The incidence of this malignant form of HAM/TSP is estimated to be around 7.9%.

Study design Case report. Objective To report an extremely rare case of stroke-mimicking, cervical spontaneous epidural hematoma (SEH) treated with tissue plasminogen activator (tPA) for hemiparesis followed by emergency cervical decompression. Summary of background data Although hemiparesis caused by cervical SEH is a relatively uncommon symptom compared with tetraparesis, such cases were often misdiagnosed as cerebral infarction and worsened by antithrombic therapy. Methods A case report and literature review are presented. Results A 71-year-old male presented with sudden neck pain followed by left-sided hemiparesis, and was believed to have had a stroke. He was administered tPA as intracranial computed tomography showed no signs of hemorrhage. However, his neurological condition continued to decline, and MRI of the cervical spine revealed a large spontaneous epidural hematoma. He subsequently underwent evacuation of the epidural hematoma and C3-6 laminoplasty, and his clinical status improved after the surgery. Conclusion To our knowledge, only three cases of cervical SEH with hemiparesis erroneously treated with tPA resulting in neurological decline because of the enlargement of an existing hematoma, including the current case, have been reported in the English literature. It is important for physicians, especially those who administer tPA treatment, to include cervical SEH in the differential diagnosis of stroke in patients presenting with sudden back pain followed by the onset of neurological deficits including hemiparesis. Level of evidence 5.

We report computed tomography (CT) features in a case of segmental thrombosis of the superior sagittal sinus. On the initial cranial CT scan, both frontal cortices showed focal areas of slightly increased attenuation. The lesions were isointense on magnetic resonance (MR) images no matter what pulse sequence was used, except on fluid-attenuated inversion recovery images, which showed curvilinear sulcal hyperintensity. On postcontrast T1-weighted images, curvilinearly enhancing structures were apparent in both frontal cortical sulci. No lesion appeared on follow-up CT or in MR images. We speculated that the areas of slightly increased attenuation in the cortices represented blood congestion in the cortical veins, venules and capillaries without serum leakage. Cranial CT images should be carefully interpreted to avoid overlooking subtle lesions.

OBJECTIVE The distribution of the Mini-Mental State Examination (MMSE) scores by age and educational level was investigated in subjects that underwent comprehensive brain examinations. METHODS This cross-sectional study included 1,414 adults without neurological disorders who underwent health-screening tests of the brain, referred to as the "Brain Dock," in our center. The MMSE scores were compared between age groups (40-44, 45-49, 50-54, 55-59, 60-64, 65-69, or ≥70 years) and educational levels [the low education level group (6-12 years) and the high education level group (≥13 years)]. RESULTS The median age was 59 years, and 763 (54%) were women. There was no significant difference in the MMSE total score between women and men. The stepwise method of the multiple linear regression analysis confirmed that a higher age [β value, -0.129; standard error (S.E.), 0.020; p

We investigated whether the topography of MRI-visible perivascular spaces (PVS) is associated with markers of specific underlying small vessel disease, including cerebral microbleed (CMB) distribution, in neurologically healthy adults.We analyzed baseline data of an ongoing Japanese population-based cohort study. PVS were rated in the basal ganglia (BG-PVS) and centrum semiovale (CSO-PVS) on axial T2-weighted MRI using a validated rating scale (score 0-4). BG-PVS degree was classified as low (score2) or high (score ≥2). CSO-PVS degree was classified as low (score3) or high (score ≥3). Independent demographic, clinical, and imaging factors for high degree of BG-PVS and CSO-PVS were investigated.A total of 1,575 neurologically healthy adults were included (mean age 57.1 years, SD 9.7; 47% male). In multivariable analyses, high degree of BG-PVS (n = 212, 14%) was associated with deep or infratentorial CMBs (odds ratio [OR] 2.77, 95% confidence interval [CI] 1.62-4.74), a marker of hypertensive arteriopathy; by contrast, high degree of CSO-PVS (n = 357, 23%) was associated with strictly lobar CMBs (OR 2.49, 95% CI 1.35-4.61), which share risk factors with cerebral amyloid angiopathy. Both high degree of BG-PVS and CSO-PVS were associated with hypertension (OR 2.03, 95% CI 1.46-2.82 and OR 1.39, 95% CI 1.07-1.81, respectively), lacunes (OR 3.35, 95% CI 1.92-5.86; OR 1.83 95% CI 1.08-3.08), and severe white matter hyperintensities (OR 2.17, 95% CI 1.42-3.31; OR 1.35, 95% CI 0.93-1.96), but these associations were stronger for high degree of BG-PVS.In a neurologically healthy cohort, the associations of PVS differ according to their topography. PVS distribution may be useful for the early detection and classification of small vessel disease.

We previously showed that global cognitive function was associated with deep or infratentorial (D/I) cerebral microbleeds (CMBs) in a Japanese healthy cohort. We continually recruited participates and performed further investigation to focus on the impact of different distributions of D/I CMBs on gradient-echo magnetic resonance imaging on global cognitive function.A total of 1392 subjects including subjects without CMBs (n = 1335), with D/I CMBs limited to the basal ganglia (BG; BG group, n = 33), thalamus (thalamus group, n = 14), and infratentorial area (infratentorial group, n = 10) were included in analyses. Subjects with strictly lobar CMBs (n = 43) were excluded, but subjects in the BG, thalamus, and infratentorial groups could also have lobar CMBs. The mini-mental state examination (MMSE) was administered to determine global cognitive function; scores less than 27 or more than 1.5 standard deviations (SDs) below the age-education-related mean were regarded as impaired.In the multivariable logistic regression analyses, hypertension and severe white matter hyperintensities were associated with the BG group and the thalamus group. In multivariable logistic regression analysis of the association between D/I CMBs classification and impaired MMSE score, only the BG group consistently displayed associations with both MMSE score less than 27 (odds ratio [OR], 5.96; 95% confidence interval [CI], 2.08-17.09) and MMSE score more than 1.5 SDs below the age-education-related mean (OR, 3.34; 95% CI, 1.24-8.99). In the BG group, adjusted mean scores of total MMSE and "attention and calculation" were lower compared with subjects without CMBs.In our study of D/I CMBs, only BG CMBs have strong association with global cognitive function. This association was independent of CMBs in other location.

The clinical importance of ovarian teratoma in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been established, however investigations of ovarian teratoma in patients with anti-NMDAR encephalitis remain limited.To clarify differences in NMDAR distribution and lymphocyte infiltration in ovarian teratoma between patients with and without anti-NMDAR encephalitis.Participants initially comprised 26 patients with ovarian teratomas. NMDAR distribution and lymphocyte infiltration in ovarian teratomas were examined using immunopathological techniques. Clinical, laboratory, and radiological data were compared between patients showing the features of encephalitis. Anti-NMDAR antibodies in the serum and cerebrospinal fluid were also measured in encephalitis patients.Neuronal tissues were obtained from ovarian teratomas in 22 patients (after excluding 4 patients who did not satisfy the inclusion criteria), and the presence of NMDA receptor subunits was revealed in all patients. Lymphocyte infiltration was more frequent in the encephalitis group (n = 3) than in the non-encephalitis group. In particular, dense B-lymphocyte infiltration near neural tissues was observed in the encephalitis group.Differences in lymphocyte infiltration in ovarian teratomas between anti-NMDAR encephalitis and non-encephalitis patients suggest the immunological importance of the ovarian teratoma as the site of antigen presentation in anti-NMDAR encephalitis.

Background and Purpose: Brain microbleeds (MBs) have been recognized to be associated with cognitive decline, and can be pathologically and topographically divided into cerebral amyloid angiopathy (CAA)-related MBs (lobar MBs) and hypertensive vasculopathy-related MBs (deep or infratentorial MBs). We assessed the hypothesis that different effects on global cognitive function might be seen with different topographical distributions of MBs. Methods: A total of 1278 consecutive adults (mean age, 58 years) without neurological disorders who had undergone health-screening tests of the brain were studied prospectively. Gradient-echo T2*-weighted MRI using a 1.5-T system was used to detect MBs. Subjects were divided into four groups: without MBs; with lobar MBs; with MBs in deep or infratentorial areas (deep MBs); and with MBs in both areas (diffuse MBs). The Mini-Mental State Examination (MMSE) was administered to determine cognitive functions. MMSE scores Results: MBs were detected in the brain for 98 of 1279 subjects (8%), including 36 subjects (3%) with lobar MBs, 48 (4%) with deep MBs, and 14 (1%) with diffuse MBs. Subnormal MMSE scores were found in 76 subjects (6%), and were significantly associated with higher age, higher systolic blood pressure, shorter duration of education, severe white matter hyperintensities, and presence of MBs. After adjusting for these related factors, presence of any MBs (odds ratio (OR), 2.29; 95% confidence interval (CI), 1.17-4.46), and topographical distributional patterns of deep MBs (OR, 2.86; 95%CI, 1.20-6.78) and diffuse MBs (OR, 5.72; 95%CI, 1.59-20.54) were significantly associated with subnormal MMSE score, whereas lobar MBs were not (OR, 0.79; 95%CI, 0.18-3.47). Scores for total MMSE and “attention and calculation” were significantly lower with deep MBs ( P P Conclusions: Regarding the presence of any MBs, hypertensive vasculopathy-related MBs appear to be the main cause of global cognitive dysfunction in neurologically healthy adults. In most middle-aged subjects, effects of CAA-related MBs on cognitive function might not yet be apparent.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with varied clinical presentations and heterogeneous histopathological features. The underlying immunological abnormalities in MS lead to various neurological and autoimmune manifestations. There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classical autoimmune disease, even though many authors state this in the description of the disease. We show the evidence that both supports and refutes the autoimmune hypothesis. In addition, we present an alternate hypothesis based on virus infection to explain the pathogenesis of MS.

The relationship between kidney dysfunction, such as chronic kidney disease (CKD), and brain morphology has attracted increasing attention, but the association between kidney dysfunction and cerebral atrophy has yet to be determined. The purpose of this study was to clarify the relationship between kidney function and a substantial degree of cerebral atrophy. A total of 610 consecutive Japanese adults without neurological disorders who had undergone health screening tests of the brain were studied prospectively. Magnetic resonance imaging was performed using a 1.5-T scanner. Using a computer-assisted processing system, the percentage of cerebrum atrophy (%Cerebrum atrophy) was calculated as an index of cerebral atrophy. Atrophy was defined as >2 s.d.s below the mean %Cerebrum atrophy. The glomerular filtration rate (GFR) was estimated using the revised equations for estimated GFR from serum creatinine in Japan. Kidney function variables included the GFR value and the prevalence of subjects with GFR

Huntington's disease is caused by polyglutamine-expanded mutant huntingtin (muhtt), an aggregation-prone protein. We identified the Pak-interacting exchange factor (alpha Pix/Cool2) as a novel huntingtin (htt) interacting protein, after screening actin-cytoskeleton organization-related factors. Using immunoprecipitation experiments, we show that alpha Pix binds to both the N-terminal of wild-type htt (wthtt) and mutant htt (muthtt). Colocalization studies revealed that alpha Pix accumulates in muthtt aggregates. Deletion analysis suggested that the dbl homology (DH) and pleckstrin homology (PH) domains of alpha Pix are required for its interaction with htt. Overexpression of alpha Pix enhanced muthtt aggregation by inducing SDS-soluble muthtt-muthtt interactions. Conversely, knocking down alpha Pix attenuated muhtt aggregation. These findings suggest that alpha Pix plays an important role in muthtt aggregation.

We report carotid ultrasonographic findings in moyamoya disease. A 44-year-old man was admitted to our hospital because of fever, headache and nausea. Neurological examination showed neck stiffness and Kernig's sign but he was otherwise normal. Brain computed tomography showed hemorrhage in the right thalamus and the lateral ventricle. Conventional carotid ultrasonography (CCU) detected marked narrowing of the right internal carotid artery (ICA) at the proximal portion without arteriosclerosis, which fulfilled the criteria of bottle neck sign, namely, the ratio of diameter of proximal portion of ICA to that of the distal portion of common carotid artery (CCA) was less than 0.5. Additionally, CCU as well as transoral carotid ultrasonography (TOCU) showed the diameter of the ICA to be smaller than that of the external carotid artery (ECA) (diameter reversal sign). These signs strongly suggested moyamoya disease. Cerebral angiography confirmed the occlusions of intracranial ICA and moyamoya vessels. Bottle neck sign and diameter reversal sign of the carotid artery on carotid ultrasonography are useful for the early detection of moyamoya disease.

A 55-year-old man with chronic alcoholism was first referred to us in 1992 because of spastic quadriparesis. T2-weighted images of MRI showed pontine and extracapsule lesions as central pontine and extrapontine myelinolysis (CPM/EPM). He had macrocytic anemia with normal serum level of vitamin B12 (B12). Gait disturbance was progressively worsened from the end of 2004 and dysuria appeared from June, 2005. Neurological examination on admission in November, 2005, showed mild impairment of recent memory, spastic paraparesis with hyperreflexia in all limbs, loss of deep sensations in lower limbs and urinary disturbance. The low serum level of B12 with marked macrocytic anemia was noted. On MRI. the pontine lesion extended to the midbrain but no abnormality was found in the spinal cord. We intramuscularly administered B12, resulting in marked improvement of both anemia and neurological symptoms. The brainstem lesion on MRI, however, was unchanged. We assume that B12 deficiency was involved in the formation of CPM/EPM and the neurological symptoms in our patient.

Objective: The fukutin gene (FKTN) is the causative gene for Fukuyama-type congenital muscular dystrophy, characterized by rather homogeneous clinical features of severe muscle wasting and hypotonia from early infancy with mental retardation. In contrast with the severe dystrophic involvement of skeletal muscle, cardiac insufficiency is quite rare. Fukuyama-type congenital muscular dystrophy is one of the disorders associated with glycosylation defects of -dystroglycan, an indispensable molecule for intra-extra cell membrane linkage. Methods: Protein and functional analyses of -dystroglycan and mutation screening of FKTN and other associated genes were performed. Results: Surprisingly, we identified six patients in four families showing dilated cardiomyopathy with no or minimal limb girdle muscle involvement and normal intelligence, associated with a compound heterozygous FKTN mutation. One patient died by rapid progressive dilated cardiomyopathy at 12 years old, and the other patient received cardiac implantation at 18 years old. Skeletal muscles from the patients showed minimal dystrophic features but have altered glycosylation of -dystroglycan and reduced laminin binding ability. One cardiac muscle that underwent biopsy showed altered glycosylation of -dystroglycan similar to that observed in a Fukuyama-type congenital muscular dystrophy patient. Interpretation: FKTN mutations could cause much wider spectrum of clinical features than previously perceived, including familial dilated cardiomyopathy and mildest limb girdle muscular dystrophy. Ann Neurol 2006;60:597– 602

We describe a 22-year-old woman with an adult-onset, slowly progressive form of subacute sclerosing panencephalitis (SSPE), who was repeatedly evaluated by brain magnetic resonance spectroscopy (MRS). The brain lesion spectrum showed a decrease in N-acetylaspartate (NAA) resonance, an increase in inositol (Ins) resonance, and an unaltered choline signal. These findings suggest neuronal loss and reactive gliosis without inflammation, consistent with brain biopsy findings showing astrocytic proliferation unaccompanied by lymphocytic infiltrates. The unusually protracted clinical course might be attributable to an absence of inflammatory infiltrates in the brain. Intraventricular interferon injection plus oral inosine pranobex treatment produced a substantial improvement in the MRS findings, suggesting the validity of monitoring MRS in SSPE.