Toshimasa Yamamoto

Clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease

Background: No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease (sCJD) has been established except for pathologic examination. Objective: To identify a reliable marker for the clinical diagnosis of MM2-type sCJD. Methods: CSF, EEG, and neuroimaging studies were performed in eight patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western blot analyses. Results: The eight cases were pathologically classified into the cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms. The cortical form was characterized by late-onset, slowly progressive dementia, cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and elevated levels of CSF 14-3-3 protein. The thalamic form showed various neurologic manifestations including dementia, ataxia, and pyramidal and extrapyramidal signs with onset at various ages and relatively long disease duration. Characteristic EEG and MRI abnormalities were almost absent. However, all four patients examined with cerebral blood flow (CBF) study using SPECT showed reduction of the CBF in the thalamus as well as the cerebral cortex. The combined form had features of both the cortical and the thalamic forms, showing cortical hyperintensity signals on DWI and hypometabolism of the thalamus on [18F]2-fluoro-2-deoxy-d-glucose PET. Conclusion: For the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease, cortical hyperintensity signals on diffusion-weighted MRI are useful for the cortical form and thalamic hypoperfusion or hypometabolism on cerebral blood flow SPECT or [18F]2-fluoro-2-deoxy-d-glucose PET for the thalamic form.

Hyperphosphorylated tau deposition parallels prion protein burden in a case of Gerstmann-Sträussler-Scheinker syndrome P102L mutation complicated with dementia

Abstract. Hyperphosphorylated tau (p-tau) deposition has been documented in a limited population of patients with Gerstmann-Sträussler-Scheinker syndrome (GSS) with particular point mutations of the prion protein (PrP) gene. Although its pathogenesis is only poorly understood, p-tau in GSS is known to be identical to that in Alzheimers disease (AD). We conducted immunohistochemical and quantitative image studies on the brain from a 44-year-old man with a 7-year history of dementia, diagnosed as having GSS with a point mutation of the PrP gene at codon 102 (GSS102), the commonest mutation in GSS. Severe spongiform degeneration and numerous PrP plaques were disclosed in the cerebral cortices and hippocampus, consistent with the diagnosis. However, rarely described in GSS102, prominent p-tau deposits as pretangles, neurofibrillary tangles and degenerating neurites were demonstrated adjacent to or around PrP plaques. β-Amyloid protein (Aβ) plaques were generally sparse and appeared invariably to be of a diffuse type. Double-labeling immunohistochemistry yielded co-localization of p-tau with PrP but not with Aβ. Most PrP plaques did not contain Aβ. These results excluded a diagnosis of concomitant AD. Quantitative analysis on a fractional area density of immunoreactive pixels demonstrated that burdens of PrP and p-tau but not Aβ were significantly correlated. These results suggest that p-tau deposition in this GSS102 is secondarily induced by PrP but not by Aβ (secondary tauopathy). Our study also suggests that p-tau deposition might be a more common phenomenon in long-standing GSS.

Fatigue in Japanese patients with Parkinson's disease: a study using Parkinson fatigue scale.

The objective of this multicenter cross‐sectional study was to determine the prevalence of fatigue and factors contributing to it in a large sample of Japanese patients with Parkinsons disease (PD). We used the 16‐item Parkinson Fatigue Scale (PFS‐16), which was designed to assess fatigue exclusively associated with PD. We carried out this study using PFS‐16, the Unified Parkinsons Disease Rating Scale, Zungs Self‐Rating Depression Scale, Parkinsons Disease Sleep Scale (PDSS), and the PD quality of life (QOL) scale (PDQ‐39) by interview using questionnaires and physical examination by neurologists in 361 nondemented PD patients. Fatigue (an average PFS score of 3.3 or greater) was revealed in 151 patients (41.8%). Multiple logistic regression analysis indicated that the significant independent variables related to the presence of fatigue were the scores of PDSS and PDQ‐39. Depression score was not a significant contributing factor. Our study revealed that the prevalence of fatigue in Japanese PD patients is as high as that in Western countries, and that fatigue is a relatively independent symptom, although sleep disturbance may be associated with fatigue. Since fatigue is significantly related to QOL reduction, therapeutic interventions including treatment of sleep disturbance are important.

Secondary SUNCT syndrome caused by viral meningitis

A 49-year-old male had been complaining of general fatigue since July 31, 2007. On August 3, he developed a headache in the forehead bilaterally, and he had a slight fever on the next day. At 3:00 a.m. on August 3, a stabbing pain lasting less than 3 seconds suddenly occurred on the right side of the forehead, cheek, and jaw. He felt pain while he was awake. The pain attacks occurred at least once every two or three minutes, and at most once every 10 seconds; attacks occurred with a frequency from 100 to 200 times per day. During the attacks, he showed dacryorrhea, swelling of the eyelids of the right eye, and rhinorrhea. The patient was not able to keep still because of his severe, stabbing headache. During the daytime of August 6, the pain moved to the right occipital and right upper auricular regions. The symptoms persisted, and he was admitted on August 7. His past history and family history were not contributory. The patient reported a stabbing headache in the right side of the forehead, cheek, and jaw, as well as in the upper auricular and occipital regions. On physical examination, Yasuo Ito Toshimasa Yamamoto Mikiko Ninomiya Yoshikazu Mizoi Kaori Itokawa Naotoshi Tamura Nobuo Araki Kunio Shimazu

Localization of laminin subunits in the central nervous system in Fukuyama congenital muscular dystrophy: an immunohistochemical investigation.

Abstract We have undertaken an immunohistochemical study of laminin subunits in the central nervous system (CNS) of fetuses and patients with Fukuyama congenital muscular dystrophy (FCMD) and of controls including five fetuses. Immunoreaction product deposits with antibodies to laminin α1, α2, β1 and γ1, and β-dystroglycan were detected on the surface and vessels of the CNS of controls. No staining with anti-α-sarcoglycan antibody was detected in the CNS. Neurons and glia did not react with any of the antibodies used. In utero expression of laminin subunits and β-dystroglycan seemed to be lower in the cerebrum than in the spinal cord. Moreover, immunostaining for laminin α2 and β1 tended to be weak on the fetal spinal cord surface. Expression of laminin subunits and dystrophin-associated proteins in the CNS may be modulated during development, as in the skeletal muscle. The distribution of immunoreaction product deposits was basically the same in FCMD and controls, although laminin α2 and β-dystroglycan expression appeared to be decreased in the CNS of the FCMD cases. Defects of the pial-glial barrier of the fetal brain surface have been considered the main cause of micropolygyria in FCMD, and these observations suggest that the co-localization and secondary loss of these proteins in association with the unknown product(s) of the FCMD gene might be involved in the CNS lesions of this disorder.

A case of α-synuclein gene duplication presenting with head-shaking movements

PARK4 is a candidate locus for familial Parkinsons disease (PD), combined with multiplication of the α‐synuclein gene (SNCA). The eventual phenotype is dependent on the copy number of SNCA. Mutations in leucine‐rich repeat kinase 2 (LRRK2) are also causative of parkinsonism. This report describes a man who presented at our hospital complaining of a stagger after running and difficulty in handling the mouse of a personal computer, having suffered tremors since his twenties. Nine months after treatment and discharge, he developed titubation and began to drag his right foot.

Dural arteriovenous fistula as a possible cause of Tolosa-Hunt syndrome: a case report.

THS is a syndrome of painful ophthalmoplegia due to nonspecific inflammation in the cavernous sinus. THS and dAVF in the cavernous sinus may show similar symptoms, but the etiologies seem to differ. Sugano et al. [1] reported a case of dAVF developing from THS, and discussed a possible role of inflammation in the development of dAVF. We report herein an additional case of dAVF in the cavernous sinus due to THS.

Characterizing restless legs syndrome and leg motor restlessness in patients with Parkinson's disease: A multicenter case-controlled study

BACKGROUND We investigated the prevalence and impact of restless legs syndrome (RLS) and leg motor restlessness (LMR) in patients with Parkinsons disease (PD) in a multicenter study. METHODS A total of 436 PD patients and 401 age- and sex-matched controls were included in this study. RLS was diagnosed based on four essential features. LMR was diagnosed when a participant exhibited the urge to move his or her legs but did not meet the four essential features of RLS. RESULTS The RLS prevalence did not differ between PD patients and controls (3.4% vs. 2.7%), while LMR prevalence was significantly higher in PD patients than in controls (12.8% vs. 4.5%). PD patients with RLS or LMR had a higher prevalence of excessive daytime sleepiness (EDS) (50.7%, vs. 6.9%), probable REM sleep behavior disorder (38.0% vs. 3.4%) and PD-related sleep problems (49.3% vs. 20.7%) than controls with RLS or LMR. RLS/LMR preceding PD onset was related to an older age of PD onset. CONCLUSION Our study revealed an increased prevalence of LMR but not RLS in PD patients. LMR could be an early manifestation of PD; however, whether LMR is within the range of RLS or whether LMR and RLS constitute different entities in PD requires further studies.

A case of sick sinus syndrome and autonomic failure with Parkinson's disease

Few case reports have described associations between autonomic failure and sick sinus syndrome.Only 1 report has presented the caseof a patient with pure autonomic failure accompanying sick sinus syndrome (Sakai et al., 1996), but electrophysiological studies (EPS) to evaluate sinus node function were not included. We therefore present herein thefirst case report of autonomic failure associated with Parkinsons disease and sick sinus syndrome, in which sinus node function was confirmed as normal by EPS.

Comparison of Dopamine Transporter SPECT and 123I-MIBG Myocardial Scintigraphy to Assess Clinical Severity in Patients With Parkinson Disease.

Purpose The aim of our study was to evaluate the use of dopamine transporter (DAT) SPECT and 123I-MIBG myocardial scintigraphy to determine the clinical severity of Parkinson disease (PD), with a focus on motor impairments affecting activities of daily living (ADLs). Methods Data for 65 consecutive PD patients who underwent both DAT and MIBG imaging were reviewed. Associations between imaging variables and Hoehn and Yahr (H&Y) staging or self-supportive care ratings were investigated. Univariate and multivariate regression analyses were performed to determine the factors associated with ADLs. Results After applying the exclusion criteria, 45 patients were analyzed (age, 73.1 ± 9.3 years; 23 males; H&Y stage 1: n = 12, stage 2: n = 14, stage 3: n = 10, stage 4: n = 5, and stage 5: n = 4; self-supportive care rating-dependent ADLs: n = 29). Dopamine transporter variables were significantly associated with the clinical severity of PD as assessed by H&Y staging, whereas MIBG variables were not. Dopamine transporter variables gradually decreased throughout progressive stages, whereas the MIBG variables changed only in the advanced stages. In a multivariate analysis including clinical and imaging variables, both lower DAT and MIBG uptakes were significantly associated with dependent ADL status (P = 0.028 and 0.034, respectively). Conclusions In patients with PD, DAT SPECT and MIBG myocardial scintigraphy were associated with ADL status; DAT SPECT was a stronger indicator of severity than MIBG myocardial scintigraphy in the early and middle stages.