Morinobu Seki

Nuclear transport impairment of amyotrophic lateral sclerosis-linked mutations in FUS/TLS.

The fused in sarcoma/translated in liposarcoma (FUS/TLS) protein was recently identified as a cause of familial amyotrophic lateral sclerosis (ALS), as well as a major component of the inclusion bodies found in subtypes of frontotemporal lobar degeneration (FTLD). These diseases now are collectively known as the novel clinical spectrum, FUS proteinopathy. ALS‐linked mutations of FUS are clustered in the C‐terminal region; however, the molecular properties of mutant FUS remain unclear. To gain insight into the pathogenesis of FUS proteinopathy, we examined the biochemical and cellular characteristics of mutant FUS in expressing cells.

Neurological response to early removal of ovarian teratoma in anti-NMDAR encephalitis

We report an 18-year-old woman with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, who developed psychiatric symptoms, progressive unresponsiveness, dyskinesias, hypoventilation, hypersalivation and seizures. Early removal of an ovarian teratoma followed by plasma exchange and corticosteroids resulted in a prompt neurological response and eventual full recovery. Serial analysis of antibodies to NR1/NR2B heteromers of the NMDAR showed an early decrease of serum titres, although the cerebrospinal fluid titres correlated better with clinical outcome. The patients’ antibodies reacted with areas of the tumour that contained NMDAR-expressing tissue. Search for and removal of a teratoma should be promptly considered after the diagnosis of anti-NMDAR encephalitis.

Camptocormia in Japanese patients with Parkinson's disease: a multicenter study.

The aim of this work was to investigate the prevalence of camptocormia and the clinical characteristics of patients with camptocormia in a large population of PD patients.

Laparoscopic Cystectomy of Ovarian Teratoma in Anti-NMDAR Encephalitis: 2 Case Reports

We present 2 case reports of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis that was successfully treated via laparoscopic ovarian cystectomy. In both cases, resection of an ovarian teratoma resulted in eventual full recovery. Although adnexectomy has been reported for tumor resection in anti-NMDAR encephalitis, we chose ovarian cystectomy to preserve ovarian function. The efficacy of cystectomy is equivalent to that of adnexectomy. This suggests that ovarian adnexectomy may not be necessary in anti-NMDAR encephalitis with ovarian teratoma.

Screening for Impaired Cognitive Domains in a Large Parkinson's Disease Population and Its Application to the Diagnostic Procedure for Parkinson's Disease Dementia

Background: Dementia is a new focus of research on improved treatment for Parkinsons disease (PD). In 2007, a screening tool for PD dementia (PD-D) was developed by the Movement Disorder Society (Level I testing), which still requires verification by a large population study. Methods: We conducted a cross-sectional and multicenter study including 13 institutions administering the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to 304 PD patients (mean age: 70.6 ± 8.3 years; mean Hoehn and Yahr stage: 2.7 ± 0.7). Results: In all, 34.5% of the patients had MMSE scores <26; 94.3% of these patients had impairments in ≥2 cognitive domains and met the criteria for probable PD-D by Level I testing. Executive dysfunction combined with attention and memory impairment was most common (51.4%). In the Level I subtests of executive function, the score for phonemic fluency declined by <50% in patients with high MoCA scores (24-30 points) and lacked specificity for PD-D. No patient had visuospatial impairment (measured by the pentagon copying subtest) alone, and the score for pentagon copying stayed at ≥70% even in patients with low MMSE scores (12-25 points), therefore lacking sensitivity for PD-D. Conclusions: Level I testing with administration of the MMSE and MoCA is a practical and efficient screening tool for PD-D. However, the phonemic fluency and pentagon copying tests should be replaced by more specific/sensitive ones when screening for PD-D.

Perfusion 123IMP‐SPECT shows reversible abnormalities in GABAB receptor antibody associated encephalitis with normal MRI

A new subtype of autoimmune encephalitis associated with antibodies against GABAB receptor was recently identified. Although immune‐mediated functional abnormalities are suggested for the pathogenesis, functional brain imaging such as perfusion SPECT has not been documented. A 62‐year‐old woman with anti‐GABAB receptor associated encephalitis underwent 123I‐IMP SPECT in the beginning and after methylprednisolone pulse therapy. Three‐dimensional stereotactic surface projection analysis was used to evaluate the cortical distribution of perfusion abnormality. The patient presented with clinical features of subacute limbic encephalitis. Antibodies to GABAB receptor were identified in her serum and cerebrospinal fluid (CSF), but no tumor was detected. Despite normal magnetic resonance imaging (MRI) findings, the first SPECT revealed hypoperfusion of the frontal, parietal and medial temporal lobes, as well as thalamus, and cerebellum. These areas are known to contain high levels of GABAB receptors. In contrast, the SPECT revealed hyperperfusion in the motor strip and left temporal lobe, which are areas related to some of the patients symptoms, including seizures, orolingual dyskinesia, and Wernicke aphasia. After treatment with pulses of methylprednisolone, the neuropsychiatric symptoms resolved and the SPECT findings showed substantial improvement in most of these regions. In conclusion, the findings suggest that immunotherapy improved the cortical dysfunction mediated by GABAB receptor antibodies.

Intracerebral Hemorrhage due to Venous Thrombosis of Developmental Venous Anomaly during Pregnancy

BACKGROUND Nowadays, developmental venous anomaly (DVA) is recognized as the most common cerebral vascular malformation. Most DVAs are diagnosed incidentally on routine brain imaging, but they are occasionally symptomatic. We report the case of a 26-year-old Japanese woman with intracerebral hemorrhage due to venous thrombosis of DVA. METHODS We examined her neurologic examinations carefully. We also observed her laboratory data, brain computed tomography (CT), and magnetic resonance imaging (MRI) findings. RESULTS She was 8 weeks pregnant and suffered from nausea, vomiturition, and appetite loss because of hyperemesis gravidarum. She presented with a sudden generalized seizure and was referred to our hospital. Brain CT showed a small hemorrhage and a tubular high-density structure compatible with an acutely thrombosed collecting vein in the right frontal lobe. T2*-weighted MRI also revealed a thrombosed collecting vein along with multiple medullary veins, which looked like caput medusa. She was diagnosed with an intracerebral hemorrhage and symptomatic epilepsy secondary to thrombosis of the DVA. After the acute phase of the disease, systemic anticoagulation therapy was administered to the patient to prevent the recurrence of venous thrombosis. We suspected that hyperemesis gravidarum with intravascular dehydration might have increased the risk of thrombosis in this patient. CONCLUSIONS Thrombosis of the collecting vein of DVA is extremely rare. This is the first report regarding DVA thrombosis during pregnancy, to our knowledge.

Comparison between MMSE and Montreal Cognitive Assessment (MoCA) for detecting cognitive impairments in patients with Parkinson's disease: A multicenter study of Keio PD database

posterior DMN connectivity normalized in the middle and posterior cingulate gyri but remained in the precuneus and retrosplenial cortex after adjusting for global cortical PiB retention in DLB. Conclusions: Patients with DLB are characterized by increases in the anterior DMN and decreases in the posterior DMN and PVN. This reciprocal change in the anterior and posterior DMN identified in patients with DLB closely resemble the DMN changes observed in AD. Although As load modifies the decreases in the middle and posterior cingulate regions in the posterior DMN, connectivity abnormalities in DLB persist even after controlling for As load. The pattern of posterior DMN and PVN connectivity decreases sparing the middle and posterior cingulate gyri after adjusting for As load is consistent with the pattern of regional hypometabolism typically observed in DLB.

Immune-mediated Neuropathy with Anti-disialosyl IgM Antibodies in Diffuse Large B-cell Lymphoma: A Case Report and Literature Review

A 36-year-old man with diffuse large B-cell lymphoma presented with polyneuropathy, and the diagnostic work-up revealed the presence of IgM antibodies against gangliosides with disialosyl residues (GD1b, GD3). He was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone and received high-dose intravenous immunoglobulin for the treatment of neuropathy. After initiating the treatments, the patients neurological impairment improved dramatically. He currently remains in complete remission without a flare-up of the polyneuropathy. Based upon our experience and other case reports of lymphoma with immune-mediated neuropathy caused by anti-disialosyl ganglioside IgM antibodies, we conclude that determining the anti-ganglioside antibody profile and beginning early treatment should be considered promptly for patients with malignant lymphoma who develop polyneuropathy.

Comparing the Montreal Cognitive Assessment with Mini‐Mental State Examination in Japanese Parkinson's disease patients

The Montreal Cognitive Assessment (MoCA) is the most suitable measure for screening cognitive impairment in Parkinsons disease (PD). However, the utility of the MoCA has not been documented sufficiently, especially in Asian populations. The present multicenter study included a large number of Japanese patients, and compared Mini‐Mental State Examination (MMSE) and MoCA scores in PD patients.