Jun-ichi Ogasawara

A Case of Postprandial Cluster-Like Headache With Prolactinoma: Dramatic Response to Cabergoline

A 17‐year‐old boy without a significant past medical history presented with recurrent cluster‐like headaches induced by meals for 3 years. Magnetic resonance images showed a pituitary tumor. Just after starting treatment with cabergoline, the headaches resolved completely and the patient has been absolutely free from such headache attacks for 2 years.

Autosomal dominant tauopathy with parkinsonism and central hypoventilation

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17T) can show various clinical phenotypes.1 We describe Japanese siblings with the intronic 10 + 14 splice site mutation of the microtubule-associated protein tau (MAPT) gene, showing parkinsonism, depression, weight loss, and central hypoventilation with reduced serotonin concentration suggested by low 5-hydroxyindole acetic acid (5-HIAA) in CSF. These clinical and biochemical features are just shared by Perry syndrome,2–4 although neither DCTN1 gene mutation nor TDP-43 proteinopathy was found. ### Case reports. A Japanese woman (III-5) (figure, A) developed clumsiness, tremor of the upper limbs, appetite loss, and apathy at age 44. She had lost 14 kilograms of body weight during 10 months. Mask-like face, hypophonic voice, bradykinesia, and muscle rigidity with predominance on the right side were observed. Deep tendon reflexes were hyperactive, especially in the right extremities with the Babinski sign. Despite levodopa treatment, her parkinsonism progressed and memory loss, disorientation, and cyanosis became apparent. Blood tests, EKG, and chest X-ray were not remarkable. Arterial blood gases showed reduced oxygen (60.3 Torr) and increased carbon dioxide (55.5 Torr). CSF analysis showed reduced 5-HIAA (5.6 ng/mL [normal 28.5 ± 7.2 ng/mL]). Brain MRI demonstrated mild atrophy in the brainstem tegmentum. Polysomnography revealed central hypoventilation with hypoxia. Although memory loss, disorientation, and …

Neuropathy in chronic graft‐versus‐host disease caused by Donor T cells

Chronic graft-versus-host disease (cGVHD) affects diverse organs, including peripheral nerves. Previous cases of neuropathy accompanied by cGVHD were diagnosed primarily based on electrophysiological studies and showed a favorable response to intravenous immunoglobulins. A case demonstrating infiltration of T cells in the sural nerve has been reported, but it remained unclear whether such neuropathy was caused by cGVHD or was coincidentally coexistent with other autoimmune diseases, including chronic inflammatory demyelinating polyneuropathy (CIDP). We describe direct invasion of the peripheral nervous system by the donor’s T cells in a recipient. A 29-year-old woman, after being diagnosed with acute lymphocytic leukemia (ALL), underwent a gendermismatched allogeneic bone marrow transplantation from her HLA-identical brother. Five months later, she developed cGVHD manifested by hyperkeratotic plaques of mouth ulceration and skin eruption, fulfilling the criteria for GVHD. She was treated with cyclosporine and prednisolone, after which all findings gradually lessened. Seven months later, she felt leg weakness and also noted numbness of all extremities, alopecia, dry eyes, and mouth ulcers. The neurological examination revealed distal-dominant muscle weakness in all limbs with areflexia. Tactile and pain sensations were diminished in all 4 limbs. Cerebrospinal fluid (CSF) analysis showed 13 mononuclear cells per microliter and elevated protein (264 mg/dl). Electromyography (EMG) revealed reduction of motor and sensory action potential amplitudes, decreased conduction velocities, and prolonged latencies with conduction block and abnormal temporal dispersion. The findings were consistent with a diagnosis of demyelinating neuropathy. After intravenous immunoglobulin treatment (400 mg/kg/day for 5 consecutive days), limb weakness gradually improved, and numbness of her extremities resolved. Thereafter, her demyelinating neuropathy relapsed 3 times, and she was treated with intravenous immunoglobulin, resulting in partial remission. After a fourth deterioration of the neurological and electrophysiological abnormalities, she was admitted to our department for a nerve biopsy. Sural nerve specimens showed a severe loss of large fibers and scattered thinly myelinated fibers. The teased fiber analysis showed segmental demyelination and irregular internode length. According to Dyck’s classification, a demyelinating process was seen in 8% of the fibers. Immunohistochemically, scattered CD4þ and CD8þ T cells were observed in the nerve bundles (Fig. 1A and B). The density of lymphocytes in the endoneurial space was 3.1/mm. Fluorescence in situ hybridization (FISH) showed that 15% of the infiltrating T cells carried both Xand Y-chromosomes (Fig. 1C and D), whereas others had two X-chromosomes. These data conclusively demonstrate that the infiltrating T cells were of donor origin, that is, from her brother. Periodic administration of immunoglobulin was effective in maintaining remission of the patient’s neuropathic deficits for 1 year thereafter. Gender-mismatched transplantation allowed us to distinguish the separation of donor and recipient cells using FISH, leading to the diagnosis of cGVHD-related neuropathy, and not CIDP. Arthritis with synovitis that developed in cGVHD after gender-mismatched transplantation for acute myelogenous leukemia has been reported. As in our patient, FISH analysis identified the donor origin of the inflammatory infiltrating T cells within the synovial tissues and confirmed the diagnosis of cGVHD.

Proton magnetic resonance spectroscopy in corticobasal degeneration and progressive supranuclear palsy

Background:  Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) each have distinctive clinical features, but diagnosis is often uncertain. Our purpose was to evaluate whether localized, single‐voxel proton magnetic resonance spectroscopy (1H‐MRS) could distinguish between typical CBD and PSP patients.

Neuromyelitis optica shows hypermetabolism in 18-fluorodeoxyglucose positron emission tomography

Neuromyelitis optica (NMO) is an idiopathic severe necrotic inflammatory disease that mainly causes optic neuritis and myelopathy. Although it usually shows typical magnetic resonance imaging (MRI), the spinal lesions in NMO might sometimes mimic neoplasms or multiple sclerosis (MS) plaques. We present two NMO patients who showed marked hypermetabolism using 18‐fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging at spinal cord lesions, corresponding to the gadolinium‐enhanced site. As MS plaques typically show hypometabolism, FDG‐PET imaging might be a useful and specific tool for the differential diagnosis of MS and NMO. Furthermore, NMO lesions should not be misdiagnosed as neoplasms simply because of the presence of hypermetabolism in FDG‐PET imaging. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759‐1961.2011.00026.x, 2012)

[Systemic vasculitic neuropathy diagnosed by means of (18)F-FDG PET CT].

We report a 43-year-old man experienced numbness in the distal portion of both legs, which progressed over following two months. Neurological examination showed hypesthesia and muscle weakness in the distal portion of both legs. No abnormal findings were seen on blood test and whole-body contrast enhanced computed tomography (CT). Histopathological findings of the sural nerve and the peroneus brevis muscle showed decreased myelinated nerve fibers with scattered myelin ovoids, vascular occlusion in the epineurium, and inflammatory cell around the arteriole in the muscle bundle. These findings suggested falling in the category as non-systemic vasculitic neuropathy (NSVN). (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) revealed the increase of FDG uptake in the rectum. Inflammatory cell infiltration was found around the arteriole with fibrinoid necrosis in the histopathological specimen of the rectal mucosal biopsy. This result represented the diagnosis as systemic vasculitis. The diagnosis of NSVN may depend on the sensitivity of diagnostic procedure, and (18)F-FDG PET CT might be a useful tool to detect small or medium-sized vasculitis.

Novel mutation in the methyltransferase domain of DNMT1 in a hereditary sensory and autonomic neuropathy patient with hearing loss, cataract, and dementia

DNMT1 encodes DNA methyltransferase 1, which is a critical enzyme responsible for conversion of unmethylated DNA into hemimethylated DNA. To date, two phenotypes produced by DNMT1 mutations have been reported, including hereditary sensory and autonomic neuropathy type IE, and autosomal dominant cerebellar ataxia, deafness and narcolepsy. We report a sporadic Japanese patient with dysautonomia, hearing loss, cataract, sensory disturbance and mild dementia. A novel missense mutation, c.4001C>T, was identified in exon 35, which encodes the methyltransferase domain of DNMT1. Until now, all reported mutations of DNMT1 were within the replication focus targeting sequence domain of DNA methyltransferase 1. This is the first report of a mutation in the methyltransferase domain of DNA methyltransferase 1. Our patient showed remarkable autonomic dysfunction along with cataract, a possible new phenotype of DNMT1 mutations.

Cytomegalovirus myositis complicated with hemophagocytic lymphohistiocytosis, acute renal failure, and colitis

A 60-years-old previously healthy man presented with acute renal failure and hemophagocytic lymphohistiocytosis (HLH). Both conditions improved after immunotherapies, but severe limb weakness with elevation of serum CK developed. Needle EMG showed myogenic changes with spontaneous activities and muscle weakness thereafter improved without adding further immunotherapies, suggesting that our patient had viral myositis. After the stabilization of limb weakness, cecal perforation occurred due to cytomegalovirus (CMV) enteritis and temporal significant change of anti-CMV IgG antibody titer was confirmed using paired serum samples. Upregulation of MHC-class I molecule and numerous regenerative muscle fibers were observed in muscle biopsy, but no evidence of direct CMV infection in muscle fibers were seen. Although CMV infection may cause either myositis, acute renal failure, HLH or colitis in individual patient, this is the first case which had been complicated by all these conditions subsequent to CMV infection.

Cortical Activation during Reading Letter String in Normal and Reverse Directions: An fMRI Study

In order to investigate the difference of cortical activation between reading letter string in normal direction and reverse direction, an fMRI study was conducted. In this study, the cortical activations responsible for Japanese string and Chinese string reading were investigated. The subjects performed normal direction reading task (read strings from left to right), and reverse direction reading task (read strings from right to left). According to the experimental results, the activated brain regions during normal direction reading task and reverse direction reading task were almost the same, besides, we found visuospatial transformation was involved in the reverse direction reading task, while this function was not significant during normal direction reading task

Study about the Cognitive Characteristic of Length by the Finger Tactile Sense-Measurement on Human Advanced Function of Brain by fMRI

In this study, in order to clarify the human advanced brain information processing mechanism on tactile cognition, we used functional MRI (fMRI) and the manufactured tactile length stimulus presentation equipment by 12 persons normal subjects identified human brain activity region to tactile length cognition without visual guidance. By the experiment result, activation regions are found in the intra-parietal sulcus (IPS), lateral occipital cortex (LOC), dorsal occipital cortex (DOC), MT/V5, Wernicke, Broca, and right dorsolateral prefrontal area. These brain activation regions showed that tactile cognition closely associated with high order vision information processing areas and language information processing areas. On the tactile length cognition, using tactile mental representation, it is accompanied also by logical intellectual judgment at the same time it makes an intuitive cognitional judgment.