Jin-ichi Nunomura

Quantitative autoradiographic distribution of glutamate receptors in the cervical segment of the spinal cord of the wobbler mouse

The reduction of glutamate content has been observed in the spinal cord of the wobbler mouse, a purported model of amyotrophic lateral sclerosis (ALS). To elucidate glutamate receptors in the wobbler spinal cord, we measured densities of N-methyl-D-aspartate (NMDA), kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) and metabotropic glutamate (mGlu) binding sites using in vitro autoradiography. In wobbler mice, NMDA, kainate, and AMPA binding sites were increased in the dorsal horn and kainate binding sites were also increased in the intermediate zone. However, mGlu binding was unchanged. These results disagree with those observed in ALS spinal cords, in which NMDA and kinate binding sites are decreased. The wobbler mouse may have the glutamate dysfunction, but in a different way from ALS.

Sporadic amyotrophic lateral sclerosis with pallido‐nigro‐luysian degeneration: A TDP‐43 immunohistochemical study

Recently, Nishihira et al. demonstrated the presence of two types of TDP‐43 pathology in sporadic amyotrophic lateral sclerosis (ALS) (Acta Neuropathol 2008; 116: 169–182). Type 1 represents the TDP‐43 distribution pattern observed in classic ALS, whereas type 2 shows the presence of TDP‐43 inclusions in the frontotemporal cortex, hippocampal formation, neostriatum and substantia nigra and is significantly associated with dementia. However, ALS with pallido‐nigro‐luysian degeneration (PNLD) is very rare. We recently encountered a case of ALS with PNLD of 9 years duration, in which the patient received artificial respiratory support for 6 years. In our case, neuronal loss and TDP‐43‐positive neuronal cytoplasmic inclusions were found in the globus pallidus, substantia nigra and subthalamic nucleus. Neither neuronal loss nor TDP‐43‐immunoreactive inclusions were found in the frontotemporal cortex and hippocampus. These findings suggest that the pallido‐nigro‐luysian system is also involved in the disease process of ALS and that ALS with PNLD is different from ALS with dementia based on the distribution pattern of neuronal loss and TDP‐43 accumulation.

Effects of duloxetine on motor and mood symptoms in Parkinson's disease: An open-label clinical experience

• Serotonin and norepinephrine transporters are capable of dopamine reuptake in the parkinsonian striatum.

Venous Cerebral Infarction in a Patient With Peripheral Hemodialysis Shunt and Occlusion of the Left Brachiocephalic Vein

Intracranial venous congestion is a rare condition in hemodialysis patients with central venous occlusion. We report a patient with cerebral venous infarction resulting from high reflex flow into the cranium induced by an arteriovenous hemodialysis shunt in the arm and occlusion of the brachiocephalic vein. This case illustrates that abnormal extracranial venous circulation should be considered when cerebral venous congestion is assumed to produce neurologic symptoms in patients with an arteriovenous shunt.

Cerebral venous thrombosis with dural arteriovenous fistulas and antiphospholipid syndrome: a case report

Dear Editor, Dural arteriovenous fistulas (DAVF) and antiphospholipid syndrome (APS) are important risk factors for cerebral venous thrombosis (CTV). We describe a young patient presenting with CVT with DAVF and APS. However, the combination of the DAVF and APS has not been reported in patients with CVT. A 38-year-old man visited our outpatient clinic because of abnormal behavior. He had no mental retardation. Two weeks before the visit, he drove into a closed ski slope and crashed his car. When he was found, he had been in the car for 2 days in the ski slope. He was confused and then transferred to a local hospital. Examinations including head CT scan showed no abnormality. His daily behavior initially appeared to be normal after the episode. However, he began to demonstrate abnormal activities such as pouring water onto salad and became unable to do easy arithmetic. He did not complain of headache and fever. He showed no nuchal rigidity on admission. He was disoriented and had bradyphrenia. Mini-mental state examination was 22/30 in which he had severe loss of recent memory. The Rey–Osterrieth figure test revealed severe verbal and visual memory deficits along with inattention. He had no abnormality in cranial nerves. D-dimer was normal and b2GPI-dependent IgG antiphospholipid antibody was 54 U/ml (\3.5 U/ml). Brain MRI revealed abnormal high signals in the bilateral thalamus (Fig. 1). Brain MR venography (MRV) revealed thrombosis in the straight sinus. Digital subtraction angiography showed DAVF from marginal tentorial arteries of bilateral internal carotid arteries, bilateral occipital arteries, tentorial branches of bilateral median meningeal arteries, and right lateral posterior choroidal artery. These DAVF flowed into the vein of Galen, and the blood flow of the DAVF regurgitated into bilateral internal cerebral veins. The vein of Galen and the straight sinus were occluded. The patient was diagnosed as CVT with multiple DAVF and APS. Anticoagulant therapy was started from the day of admission, but he fell into stupor. Three times of transarterial embolisation (TAE) were performed on the DAVF and then the DAVF was surgically resected. The specimen showed arteriovenous shunting between dural arteries and veins with multilayered elastic tissue in venous walls. After the operation, attention and verbal memory on the Rey–Osterrieth figure test remarkably improved. A followup brain MRI showed a decrease in the area of abnormal intensity (Fig. 1). He was discharged without aid. We described a patient with CVT, in which cognitive disorder was a prominent symptom due to venous infarction of the bilateral thalamus by the occlusion of the straight sinus. The patient had DAVF draining into the vein of Galen. Additionally APS was found in our patient. APS is also one of the major risk factors of CVT [1]. DAVF and CVT have been closely related to each other. However, it remains to be elucidated whether DAVF is the Y. Miki (&) M. Tomiyama A. Arai T. Kimura C. Suzuki J. Nunomura M. Baba Department of Neurology, Aomori Prefectural Central Hospital, Higashi Tsukurimichi 2-1-1, Aomori, Japan e-mail: yasuomiki@hotmail.com

Downbeat nystagmus as an initial clinical sign in spinocerebellar ataxia type 6

Dear Editor, Spinocerebellar ataxia type 6 (SCA6) is characterized clinically by progressive cerebellar ataxia with cerebellar atrophy, dysarthria, and oculomotor disturbance, and genetically by CAG repeat expansion in the α1A-voltage-dependent calcium channel gene (CACNA1A) on chromosome 19p13 [1]. SCA6 accounts for 15% of all cases of SCAs worldwide [1]. Downbeat nystagmus (DBN) is defined as a vertical spontaneous nystagmus, marked by downward fast phases [2], and is frequently observed in SCA6 [3]. However, the presence of DBN as an initial clinical sign for SCA6 is unknown [3, 4], particularly as accurate SCA6 diagnosis is difficult in isolated DBN cases. Herein, we report an SCA6 patient with DBN as an initial clinical sign, who lacked all other clinically distinguishing signs and symptoms of SCA and who had no family history of SCA. A 71-year-old woman visited our hospital because of positionalor motion-induced dizziness followed by continuous dizziness over 2 months. Her medical history was hypertension, dyslipidemia, and Graves’ disease at 2 years prior, but no cancer. She did not drink alcohol. She had been taking nifedipine, fluvastatin, and thiamazole for 2 years. She had no family history of SCA. Initial neurological examination revealed isolated DBN, but no cerebellar ataxia and dysarthria. The DBN amplitude increased during lateral gaze. Smooth pursuit and saccade were normal. She had no other cranial nerve disturbance, sensory disturbance, or limb weakness, and her deep tendon reflex and gait were normal. As she had only isolatedDBNwithout cerebellar ataxia and no family history of SCA, we initially considered her illness as cerebellar tumor, Arnold–Chiari malformation, cerebrovascular disease, paraneoplastic neurologic syndromes, or Wernicke’s encephalopathy. Laboratory studies showed normal vitamin B1, B12, and glucose. Serum electrolytes, renal and liver function, and complete blood count were normal. Carcinoembryonic antigen, alpha-fetoprotein, pro-gastrin-releasing peptide, and thyroid-stimulating hormone were within normal limits. No onconeural antibodies (anti-glutamic acid decarboxylase, Zic4, titin, SOX1, recoverin, Tr, Hu, Yo, Ri, Ma2/Ta, CV2, amphiphysin) were detected in serum. Chest radiograph andwhole-body computed tomography scans were unremarkable. No cerebellar or brainstem atrophy was observed on magnetic resonance imaging (MRI) (Fig. 1a– c). Therefore, initial differential diagnosis was excluded on the basis of laboratory and imaging studies. As the etiology of DBN was undetermined, we tentatively diagnosed the patient as idiopathic DBN and started clonazepam, betahistine, difenidol, and ifenprodil therapy. However, she visited the hospital irregularly, as these treatments failed to improve her symptoms. Three years after the initial visit, neurological examination revealed DBN in the sitting and supine positions (Online Resource 1). The DBN amplitude increased in lateral gaze and decreased in downgaze. Smooth pursuit was slightly saccadic in all directions, while saccade was normal. The horizontal vestibulo-ocular reflex was impaired. Cancelation of the vestibulo-ocular reflex was also impaired (Online Resource 1). Furthermore, the patient had a mild wide-based gait, and she was unable to perform tandem stand with eye open and stand on one foot. Nevertheless, limb Electronic supplementary material The online version of this article (doi:10.1007/s10072-017-2973-y) contains supplementary material, which is available to authorized users.

The Differential Diagnosis of Acute Onset Truncal Ataxia: The Importance of Dysgeusia in Miller Fisher Syndrome

Miller Fisher syndrome (MFS) can be difficult to diagnose, particularly in mild cases where some of the standard triad of symptoms (external ophthalmoplegia, ataxia, and loss of deep tendon reflex) are absent. We herein report a case of the incomplete form of MFS diagnosed in a 54-year-old Japanese man who presented only with ataxia symptoms and was positive for the anti-GQ1b antibody. However, the patient also suffered from dysgeusia, a significant impairment of taste perception. We propose that dysgeusia in acute-onset ataxia cases may constitute an important clinical feature to aid in the diagnosis of the incomplete form of MFS.

Myelin Oligodendrocyte Glycoprotein-IgG-positive Recurrent Bilateral Optic Papillitis with Serous Retinal Detachment: A Case Report

Autoantibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been detected in inflammatory demyelinating central nervous system diseases. A 30-year-old woman had blurred vision, marked optic nerve disc swelling, serous retinal detachment at the macular on optic coherence tomography, and MOG-IgG seropositivity. The patient was thought to have optic papillitis associated with MOG-IgG. Her symptoms rapidly improved after high-dose methylprednisolone therapy. We hypothesize that serous retinal detachment was secondary, arising from optic papillitis. This is the first report of the concurrence of optic papillitis with MOG-IgG and serous retinal detachment. MOG-IgG should be tested in patients with marked optic disc swelling.

Clinical diagnostic utility of contrast-enhanced three-dimensional fluid-attenuated inversion recovery for selection of brain biopsy sites in neurosarcoidosis: A case report

Neurosarcoidosis is difficult to diagnose, because definite diagnosis requires detailed histology of the central nervous system. Three-dimensional contrast-enhanced fluid-attenuated inversion recovery (CE-FLAIR) is more useful for detecting leptomeningeal lesions compared with 3D CE-T1 weighted imaging. However, the clinical diagnostic utility of 3D CE-FLAIR for neurosarcoidosis is unclear. We describe a case of a 46-year-old Japanese woman who was admitted to our department due to chronic headache with fever and diplopia. Using 3D CE-FLAIR, we performed brain biopsy from right cerebellar lesion. The histological examination revealed typical non-caseating granulomas, indicating neurosarcoidosis. Our findings suggest that 3D CE-FLAIR may detect leptomeningeal lesions that are candidates for biopsy in chronic meningitis undetermined etiology.

Arterial Spin Labeling Imaging of a Giant Aneurysm Leading to Subarachnoid Hemorrhage following Cerebral Infarction

An 83-year-old Japanese man was admitted with dysarthria and right hemiparesis. He had had a large intracranial aneurysm on the left internal carotid artery 5 years before admission and had been followed up under conservative treatment. On admission, diffusion-weighted imaging revealed a hyperintense signal on the left anterior choroidal artery territory. Time-of-flight magnetic resonance angiography demonstrated poor visibility of the middle and anterior cerebral arteries and the inferior giant aneurysm, suggesting distal emboli from aneurysm thrombosis or a reduction of blood outflow due to aneurysm thrombosis. Arterial spin labeling (ASL) signal increased in the giant aneurysm, suggesting blood stagnation within the aneurysmal sac, and decreased in the left hemisphere. We diagnosed cerebral infarction due to aneurysm thrombosis, and started antithrombotic therapy. On day 2, he suddenly died of subarachnoid hemorrhage due to rupturing of the giant aneurysm. When thrombosis occurs in a giant aneurysm, increasing ASL signal within the aneurysm and decreasing ASL signal with poor visibility on magnetic resonance angiography in the same arterial territory may indicate the danger of impending rupture of the giant aneurysm.