We studied the mechanism underlying seizure induction in patients with chronic subdural hematoma. In our study population of 1,009 patients with chronic subdural hematoma, 26 (2.6%) had seizure-related complications. Six of them had already been diagnosed with epilepsy (4 patients) or suspected of having secondary epilepsy (2 patients) after experiencing traffic accidents or cerebral bleeding. Twenty patients (seizure group) had been tentatively diagnosed as having hematoma-induced convulsion. Of the remaining 989 patients without convulsion, 40 randomly sampled patients were included in the non-seizure group by matching with clinical terms. Intergroup comparisons showed that patients with dementia were more common in the seizure group than in the non-seizure group; however, no intergroup differences were observed for other clinical parameters. Radiological examinations showed that bilateral hematomas were relatively more common and sulcal hyperintensity on FLAIR MR images was significantly more frequent in the seizure group than in the non-seizure group. Interestingly, many patients presenting with sulcal hyperintensity exhibited mixed-density hematomas on CT images. These findings suggest the mechanism by which hematoma content infiltrates into the brain parenchyma and the subsequent induction of convulsions by the stimulatory component.

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A 76-year-old man was admitted to our hospital presenting with fever, redness and pain in both the periocular regions, and disturbance of consciousness. He had neck stiffness, and cerebrospinal fluid analysis suggested aseptic meningoencephalitis. Laboratory tests showed increased levels of C-reactive protein, soluble IL-2 receptor (sIL-2R) and MPO-ANCA. Magnetic resonance imaging revealed hyperplastic bone marrow in the clivus and cervical vertebra. Although T-cell receptor gene rearrangement was detected in the bone marrow blood, bone marrow biopsy of the ilium showed no malignant findings. Then he experienced bilateral auricular inflammation and painful erythema of the ankle. A leg skin biopsy demonstrated neutrophilic infiltration into the dermis with no signs of vasculitis. His HLA-type was defined as Cw1. He was subsequently diagnosed with neuro-Sweet disease. Intravenous administration of methylprednisolone (1,000 mg/day) for 5 days and subsequent oral intake of prednisolone (60 mg/day) improved his symptoms. When the prednisolone dose was reduced to 30 mg/day, his symptoms returned and a new lesion was detected in the splenium of the corpus callosum. Upon additional treatment with cyclosporine, the prednisolone dose could be reduced without symptom relapse; sIL-2R and MPO-ANCA levels also decreased to normal. The present case suggested that the activity of neuro-Sweet disease may be associated with myeloid hyperplasia, T-cell receptor gene rearrangement and the amounts of soluble interleukin-2 receptor and MPO-ANCA.

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A 14-year-old girl was referred to us with severe migraine-like headaches associated with vomiting and right homonymous hemianopsia. On admission, MRI examination showed high signals in the left occipital cortex and subcortex on T₂-weighted images, without reduction of apparent diffusion coefficient suggestive of cerebral infarction. Her EEG demonstrated periodic sharp waves in the left posterior region, and laboratory tests revealed she had increased levels of lactic and pyruvic acid both in blood plasma and CSF. Gene analysis confirmed mitochondrial DNA A3243G mutation. Based on this data, we diagnosed her as having mitochondrial myopathy, encephalopathy, lactic acidosis and a stroke-like episode (MELAS). L-arginine infusion was unsuccessful for her severe headaches, which remained prolonged. She received a low dose (0.05 mg/kg/h) midazolam infusion, resulting in immediate improvement and the disappearance of headaches and abnormal EEG findings. By the age of 18, she had been readmitted eight times for stroke-like episodes accompanied by headaches. While L-arginine infusions alleviated her headaches when administered on day 1 of her episodes, they were not effective when started on or after day 2. Her L-arginine-resistant headaches were relieved by midazolam. Although the pathogenesis of headaches in MELAS is still unknown, neuronal hyperexcitability and trigeminovascular activation are considered important. Midazolam may play a role in suppressing neuronal hyperexcitability and trigeminovascular activation. Treatment with midazolam is advisable for headaches in patients with MELAS, in the event that L-arginine therapy is unsuccessful.

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We report a 65-year-old female with meningeal involvement in Wegener’s granulomatosis (WG). At 52 years of age, she was diagnosed as having WG by lung biopsy and elevated proteinase3 anti-neutrophil cytoplasmic antibody titer. She had been maintained on prednisolone. Three weeks before admission, she developed deterioration of mental status. On examination, neurological abnormalities included right hemiparesis, confusion, memory loss, psychomotor slowing and agraphia. CSF was normal. Diffusion-weighted images (DWI) showed high intensity lesions in the subarachnoid space over the left hemisphere. Fluid attenuated inversion recovery (FLAIR) images showed high intensity signal in the subarachnoid space with mild swelling of the cortex and abnormal meningeal enhancement corresponding to the high intensity area on DWI. She was treated with intravenous administration of methylprednisolone (1,000 mg/day for 3 days) and cyclophosphamide, and gradually improved in symptoms and abnormal hyperintensity on DWI. Involvement of the meninges in WG is rare. The dura mater is involved more frequently than the pia mater. Pathological findings of the meninges in WG has been reported to be granulomatous inflammation. Restricted diffusion in the subarachnoid space has been described to occur in a viscous mixture of proteins and inflammatory cells, similarly to the DWI hyperintensity in pyogenic abscesses. In our case, abnormal hyperintensity on DWI was interpreted as a dense inflammatory infiltrate in the leptomeninges. Therefore, DWI and FLAIR image have been shown to be useful for demonstration of leptomeningeal lesions in WG.

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An 18-year-old man was admitted to our hospital because of convulsive seizure. He had psychomotor retardation and intellectual disability from childhood, and had been diagnosed with attention deficit-hyperactivity disorder when he was 12 years old. He showed mental deficit (Wechsler Adult Intelligence Scale-Revised: IQ 52) and tendon hyperreflexia without pathological reflexes, but no involuntary movements or self-injurious behavior. As he had hyperuricemia, we measured the activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) and adenine phosphoribosyltransferase (APRT) in erythrocytes. While HPRT activity had decreased to 57.4% of normal, APRT activity had increased to 140.5% of normal. Genetic analysis revealed a single-base substitution (c.179A>G) in the third exon of the HPRT gene, which resulted in a missense mutation (p.H60R) of the 60th amino acid. His mother was a heterozygous carrier of this mutation and presented partial deficiency (73.3%) of HPRT activity. Lesch–Nyhan disease is a neurogenetic disorder caused by complete deficiency of the enzyme HPRT. Variant forms of the disease caused by partial deficiency of HPRT do not show the typical clinical features, or show only mild neurological manifestations; these diseases are jointly referred to as HPRT-related neurological disease (HRND). The present case was unique in that the patient diagnosed as having HRND showed relatively higher HPRT residual activity in erythrocytes.

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A 39-year-old man was admitted to our hospital because of left frontal subcortical hemorrhage.When he was 22, he underwent an operation for aortic dilatation and aortic valve regurgitation, and he had been taking warfarin since then. At that hospital, he was diagnosed with Marfan syndrome (MFS) on the basis of his clinical features, but the diagnosis was not confirmed genetically. Head radiological imaging did not reveal the abnormal blood vessels causing subcortical hemorrhage, but T₂* magnetic resonance imaging showed many micro-bleeds in the subcortical areas and basal ganglia. Moreover, cerebral angiography showed marked tortuous carotid and vertebral both arteries in his neck; these findings suggested the possibility of Loeys-Dietz syndrome. Genetic analysis revealed a single-base substitution (c.3713-3C>G) at the −3 position in the 29th intron of the FBN1 gene, encoding the fibrillin-1 protein. This mutation was not observed in his parents but was detected in his two sons who manifested the physical features of MFS. Therefore, this mutation was considered to be a de novo mutation exhibiting a new pathogenic mechanism involving abnormal splicing. The presented case is unique in that the patient with MFS showed subcortical hemorrhage and had a novel de novo mutation in the FBN1 gene.

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A 30-year-old woman was admitted to our hospital because of intractable orbital pain and ptosis on the left side. On admission, she had left oculomotor, ophthalmic and maxillary nerves palsy. MRI revealed a contrast enhanced lesion of the left oculomotor and trigeminal nerves through the covernous sinus and orbita. We diagnosed her condition as Tolosa-Hunt syndrome. The orbital pain was resolved within 48-hours by the pulse therapy with intra-venous methylpredonisolone. The cranial nerve palsy was gradually improved, but never reached complete remission. The left oculomotor and trigeminal nerves also remained enhanced on MRI until 200 days from the onset. Although there have been few reports to demonstrate the contrast enhancement of cranial nerves in Tolosa-Hunt syndrome, these MRI findings may be a specific indicator of the pathological process.

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A 68-year-old man, with a history of type 2 diabetes mellitus and chronic kidney impairment, had been suffering from progressive knee joint contracture and dysesthesia of the lower extremities for 4 years. When he walked, his knees remained bent owing to contracture of the knee joints. There was no evidence of muscle pseudohypertrophy, intramuscular nodules, or muscle weakness. Clinical examination revealed IgA λ M-protein, reticular high-signal intensity lesions demonstrated by magnetic resonance T₂-short TI IR(STIR) imaging of the lower extremity muscles, and a mixture of neurogenic and myogenic changes demonstrated by needle electromyography. A biopsy specimen from the vastus lateralis muscle identified Aλ amyloid deposits around the vessels, establishing a diagnosis of amyloid myopathy based on systemic AL amyloidosis. This case demonstrated that joint contracture and reticular lesions shown by magnetic resonance STIR imaging of the muscles can alert the physician to consider muscle biopsy to investigate deposition of amyloid in the skeletal muscles even in the absence of muscle pseudohypertrophy or weakness, both of which are characteristic of amyloid myopathy.

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BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy; symptoms include distal wasting and weakness, usually with some sensory impairment. The clinical course is typically benign and the disease is not life threatening; however, in some cases, severe phenotypes include serious respiratory distress. CASE REPORT: Here we describe a 45-year-old woman with a long course of motor-dominant neuropathy. Distal weakness appeared in childhood and became worse with age. After a diagnosis of CMT type 2, the symptoms progressed, and in her fourth decade, facial and respiratory muscle weakness appeared, ultimately requiring non-invasive mechanical ventilation. There was no family history of CMT. Comprehensive analysis of known CMT-related genes revealed a novel heterozygous c.815T>A, p.L218Q mutation in glycyl-tRNA synthetase (GARS), a causative gene for both CMT type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V). This mutation was considered pathogenic based on molecular evidence; notably, it was unique in that all other reported GARS mutations associated with severe phenotypes are located in an anticodon-binding domain, while in this case in an apparently non-functional region of the GARS gene. Not a simple loss-of-function mechanism, but rather gain-of-function mechanisms have also been reported in GARS mutations. This case provided useful information for understanding the mechanism of CMT2D/dSMA-V.

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A 72-year-old man was transported to our emergency department after rear-ending another vehicle. He presented with acute left hemispatial neglect, left hemianopsia, and mild left hemiparesis. Computed tomography (CT) on admission showed a calcified embolus in the right middle cerebral artery. After intravenous thrombolytic therapy, the patient showed drastic improvement of neurological deficits. Follow-up CT showed disappearance of embolus, but distal migration of emboli to the downstream of the right middle cerebral artery was seen, sparing the massive territory of the right middle cerebral artery. Carotid duplex sonography and 3-dimensional CT angiography showed a calcified plaque with ulceration at the origin of the right internal carotid artery, representing the presumptive origin of the emboli. We report a rare case of effective intravenous thrombolysis for calcified cerebral embolism from the carotid artery. Further consideration of the mechanism, efficacy, and indication of intravenous thrombolysis for calcified cerebral emboli is needed.

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[in Japanese]

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