Mitsuyoshi Ayabe

Therapeutic effect and mechanism of repetitive transcranial magnetic stimulation in Parkinson's disease

Abstract The therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) on clinical performance was assessed by a double-blind study in 9 patients with Parkinsons disease (PD). Nine other patients underwent sham stimulation as controls. The modified Hoehn and Yahr (H&Y) staging scale, the Schwab and England Activities of Daily Living (ADL) scale, and the Unified Parkinsons disease rating scale (UPDRS) were used to assess changes of clinical performance. Patients were assessed prior to and following 2 months of rTMS. In addition, the mechanism of rTMS was investigated by dopamine and homovanillic acid (HVA) in the lumbar cerebrospinal fluid (CSF) of 17 patients before and after therapeutic rTMS for three or four months. rTMS was applied manually to the frontal areas 60 times per session, i. e., 30 times per side using a large circular coil, a pulse intensity of 700 V, and a frequency of 0.2 Hz. Sessions were continued once a week for 2 months. The 9 control patients showed no changes of symptoms between the initial evaluation and that after 2 months of sham rTMS. In contrast, all 9 patients receiving rTMS showed a significant decrease of the modified H&Y and UPDRS scores after 2 months, while the Schwab and England ADL Scale scores increased significantly. In the second CSF sample from patients receiving rTMS, HVA showed a significant decrease These results suggest that rTMS is beneficial for the symptoms of Parkinsons disease and that it may act via inhibition of dopaminergic systems.

A case of adult-onset Alexander disease with Arg416Trp human glial fibrillary acidic protein gene mutation

Heterozygous point mutations in the coding region of the human glial fibrillary acidic protein (GFAP) gene have been reported in patients with various forms of Alexander disease (AD). We report a case of genetically confirmed adult-onset AD with palatal myoclonus, pyramidal tract signs, cerebellar signs, and marked atrophy of the medulla oblongata and spinal cord, autonomic dysfunction and heterozygous R416W GFAP mutation. Interestingly, this R416W mutation has also been reported in both infantile and juvenile forms of Alexander disease. The fact that a R416W mutation causes various types of AD suggests that clinical severities of AD are due not only to the different sites and nature of mutations in GFAP, but also to other modifying factor(s).

Differentiation of herpes simplex virus 1 and 2 in cerebrospinal fluid of patients with HSV encephalitis and meningitis by stringent hybridization of PCR-amplified DNAs

Differentiation of herpes simplex virus (HSV) types 1 and 2 in cerebrospinal fluid of 17 patients with serological1y diagnosed HSV encephalitis and meningitis or acute limbic encephalitis was determined by stringent hybridization of polymerase chain reaction — amplified DNAs. Ten of 17 patients were positive; six with HSV 1 isolates and four with HSV 2 isolates. We detected HSV type 1 in two cases of meningitis, although meningitis is generally thought to be caused by type 2. Additionally, HSV type 2 was found in one case of acute adult encephalitis, which is generally due to HSV type 1. HSV DNAs could be detected for over I month after onset, although our patients included several prolonged and recurrent cases. HSV DNA genomes were not detected in three cases of acute limbic encephalitis. Our study indicates that this method can be used for type differentiation in HSV CNS infections.

Hereditary motor and sensory neuropathy with proximal dominancy in the lower extremities, urinary disturbance, and paroxysmal dry cough

We studied a four-generation pedigree of a Japanese family with hereditary neuropathy to elucidate the genetic basis of this disease. Twelve members of the family were enrolled in this study. The clinical features were neurogenic muscle weakness with proximal dominancy in the lower extremities, sensory involvement, areflexia, fine postural tremors, painful muscle cramps, elevated creatine kinase levels, recurrent paroxysmal dry cough, and neurogenic bladder. We performed a genome-wide search using genetic loci spaced at about 13 Mb intervals. Although nine chromosomes (1, 3, 4, 5, 6, 10, 17, 19, and 22) had at least one region in which the logarithm of odds (LOD) score was over 1.0, no loci fulfilled the criteria for significant evidence of linkage. Moreover, we analyzed an extra 14 markers on 3p12-q13 (the locus of hereditary motor and sensory neuropathy, proximal dominant form) and an extra five markers on 3p22-p24 (the locus of hereditary sensory neuropathy with chronic cough) and observed LOD scores of <-3 on both 3p12-q13 and 3p22-p24. Mutation scanning of the entire coding regions of the MPZ and PMP22 genes revealed no mutations. We conclude that the disorder described here is a newly classified hereditary motor and sensory neuropathy with autosomal dominant inheritance.

A case of adult influenza A virus-associated encephalitis: magnetic resonance imaging findings.

A 27‐year‐old man presented with fever, convulsive seizure, and sudden impairment of consciousness. Magnetic resonance imaging (MRI) abnormalities were found in the bilateral thalami, including the brain stem and white matter. The possibility of a previous influenza A virus infection was considered, and cerebrospinal fluid cells and interleukin‐6 were elevated. The MRI findings closely resembled those found in cases of childhood acute necrotizing encephalopathy (ANE). The present case suggests that adult influenza A virus‐associated encephalitis/encephalopathy or ANE can occur during winter influenza epidemics.

Inflammatory myopathy associated with hepatitis C virus infection: a report of four cases

Abstract Four patients with inflammatory myopathy positive for anti-hepatitis C virus are described. One male and three females are included in this report. Mean age of the four patients was 50 years (range 42–60 years). They were referred to our hospital with muscle weakness or myalgia. Active hepatitis C virus infection was confirmed by the detection of hepatitis C virus RNA with the polymerase chain reaction method in sera of these patients. Serum muscle enzymes, such as creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and aldolase were elevated. Inflammation in the muscle tissue was demonstrated in the muscle biopsy specimens from these patients. The patients received prednisolone and symptoms and elevated muscle enzymes were improved. It is suggested that hepatitis C virus might be one of the possible etiologic factors responsible for inflammatory myopathy.

Symmetrical brainstem encephalitis caused by herpes simplex virus

We describe a 53-year-old man with herpes simplex virus (HSV) brainstem encephalitis diagnosed based by positive HSV immunoglobulin M antibodies from cerebrospinal fluid. The MRI findings of this case had three unique features. First, the lesions were symmetrical. Second, the lesions may have been associated with reactivation of HSV infection in the region of the trigeminal nerve. Third, diffusion-weighted and apparent diffusion coefficient (ADC) imaging, conducted for the first time on an HSV brainstem encephalitis case, suggested that the lesions were associated with vasogenic edema.

Non-Herpetic Acute Limbic Encephalitis: A New Subgroup of Limbic Encephalitis?

Hiroshi Shoji1, Noriyuki Kimura2, Toshihide Kumamoto2, Takashi Ichiyama3 and Yukitoshi Takahashi4 1Division of Neurology, St. Mary Hospital, Fukuoka 830-8543, 2Department of Internal Medicine III, Faculty of Medicine, Oita University, Oita, 3Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Yamaguchi, 4National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka Japan

Anhedonia in Japanese patients with Parkinson's disease: Analysis using the Snaith-Hamilton Pleasure Scale

BACKGROUND Anhedonia, a lowered ability to experience physical or social pleasure, has recently been recognized as a non-motor symptom of Parkinsons disease. OBJECTIVE To identify the frequency of anhedonia and the factors influencing hedonic tone in Japanese patients with Parkinsons disease. PATIENTS AND METHODS We recruited 86 consecutive outpatients with a clinical diagnosis of PD attending two Japanese hospitals (one university hospital and one community hospital) in February 2010. We used the self-rating Snaith-Hamilton Pleasure Scale (SHAPS) translated into Japanese language from the original English version to assess and quantify hedonic tone as a subjectively experienced phenomenon. We studied the association of anhedonia with the variables age, age at onset, gender, disease duration, disease severity and antiparkinsonian drugs. RESULTS Thirty-nine patients (45%) were male and 47 (55%) were female. Mean age was 72.01±9.07 (49-89) years, with mean age at onset of 64.93±11.42 (31-88) years. Mean disease duration was 7.20±5.54 (1-23) years. The mean Hoehn and Yahr scale was 2.76±0.78. The mean SHAPS score of the total sample was 1.19±1.86. The SHAPS score of 14 patients (16.3%) was 3 or more, indicating anhedonia. The mean SHAPS score was lower in patients taking pramipexole (0.58±0.97) than in patients not taking pramipexole (1.57±2.16). Multiple linear regression analysis identified pramipexole as a significant negative influencing factor on the SHAPS score, while disease severity and entacapone treatment were identified as positive influencing factors. The age, onset age, gender, disease duration, and use of pergolide, amantadine, zonisamide, selegiline, anticholinergic agents and droxidopa did not significantly affect the SHAPS score. CONCLUSION Anhedonia is not rare non-motor symptom in Japanese patients with Parkinsons disease. This study suggests an anti-anhedonic property of pramipexole.

Bell-shaped sensory impairments of all modalities in a neurosarcoidosis patient

We describe a 45-year-old man with neurosarcoidosis complaining of bell-shaped tightening and pain with sensory disturbance of superficial and deep sensations. The patient showed subacute progressive sensory impairment in bilateral C7-Th12 dermatomes. Triceps and patellar tendon reflexes were decreased. Chest X-ray revealed bilateral hilar lymphadenopathy without pleural effusion. There was abnormal accumulation of gallium in the bilateral hilar lymph nodes, parotid glands, and lacrimal glands on scintigraphy. Examination of bronchoalveolar lavage fluid showed an elevated CD4/CD8 ratio. Transbronchial lung biopsy showed non-caseating granulomas with many epitheloid cells and occasional Langhans giant cells without any necrotic lesion. The tuberculin reaction was negative, and elevation of serum lysozyme and IgG level were seen. These findings fulfilled the clinical criteria for sarcoidosis. Spine MRI demonstrated no abnormality. Studies of short-latency somatosensory evoked potentials showed delayed N13 latency and absent N19 and N28 potentials bilaterally. A nerve conduction study revealed no abnormality. The patients muscle strength was normal through the entire clinical course. Therefore, we consider that his sensory impairment was caused by peripheral neuropathy, especially in the dorsal root region. Neurosarcoidosis is important for differentiating bell-shaped sensory impairments of all modalities.