A 22-year-old man had had difficulty running fast since about he was 10 years old. In June 2011, he was referred to us because of worsened unsteady gait. A neurological examination revealed mild ataxic speech, weakness of the four limbs, with spasticity, and pes cavus. Magnetic resonance T₂-weighted images showed multiple high-intensity lesions in the bilateral periventricular white matter, brainstem, and thoracic spinal cord. Peripheral nerve conduction studies revealed marked motor conduction velocities were markedly reduced and sensory nerve velocities were not evoked in the upper and lower limbs. A sural nerve biopsy showed highly active demyelinating lesions. The patient was treated with high-dose steroid therapy (intravenous methylprednisolone, 1,000 mg/day × 3 days) followed by self-injection of interferon β. With these treatments, his symptoms gradually improved. In this case, we could not detect the causative factors, and all autoantibodies tested, except for the anti-neurofascin antibody, were negative. The anti-neurofascin antibody might induce demyelination in the central and peripheral nervous systems. However, in the literature, the evidence of an association between this antibody and these clinical characteristics is not conclusive. We need more studies on the pathogenesis of combined central and peripheral demyelination to establish more effective therapies.

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A 62-year-old man experienced pain and swelling in both of his auricles. One and a half months later, he was referred to us because of a memory disturbance. A neurological examination revealed disorientation and recent memory impairment. Diffusion-weighted and fluid-attenuated inversion recovery magnetic resonance images showed high intensity and swelling lesions in the bilateral medial temporal regions. In cerebrospinal fluid, mononuclear cell counts and total protein concentration were increased, but a herpes polymerase chain reaction was negative. Thus, he was suspected to have non-herpetic acute limbic encephalitis (NHALE). In addition, relapsing polychondritis (RP) was suspected because of the bilateral auricular chondritis and type-II collagen antibody positivity in the serum. He was treated with high-dose steroid therapy (two cycles of intravenous methylprednisolone, 500 mg per day for 3 days), which was followed by oral steroid therapy. With these treatments, his symptoms, including the painful auricular swelling and memory disturbance, gradually improved. This case exhibited anti-glutamate receptor (GluRε2) antibody positivity in both serum and cerebrospinal fluid, but anti-N-methyl-D-aspartate glutamate receptor antibody (NR1 + NR2) by cell-based assay negative in cerebrospinal fluid. Although a vascular mechanism of NHALE that is associated with RP has been suggested in the literature, this autoantibody might have induced NHALE as the mechanism of neuronal damage to target neuron in our case. More studies on the pathogenesis of NHALE that is associated with RP are needed.

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We, herein, report two independent cases with hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) inherited in an autosomal dominant fashion. Their common clinical features are slowly progressive proximal dominant muscular atrophy, fasciculations and mild to moderate distal sensory disturbance with areflexia. Nerve conduction study revealed an absence of sensory nerve action potentials, in contrast to almost normal compound muscle action potentials. Gene analysis in both patients elucidated heterozygous mutation (c.854C>T, p.Pro285Leu) in the TFG, which is an identical mutation, already described by Ishiura et al. Okinawa and Shiga are two foci of HMSN-P in Japan. Eventually, one patient is from Okinawa and the other is from a mountain village in Shiga prefecture. When we see a patient who has symptoms suggestive of motor neuron disease with sensory neuropathy, HMSN-P should be considered as a differential diagnosis despite the patient’s actual resident place.

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Here we report a case of a 68-year-old man with severe stenosis of the right middle cerebral artery (MCA) following herpes zoster ophthalmicus. He presented with right-sided ptosis and ophthalmoplegia 2 months after herpes zoster ophthalmicus. Cerebrospinal fluid (CSF) analysis revealed monocytosis, increased protein levels, and positivity for herpes zoster virus immunoglobulin M (IgM). Brain magnetic resonance imaging (MRI) revealed a small asymptomatic infarct in the right basal ganglia and severe stenosis of the right MCA (M1 segment). One month later, he presented with muscle weakness of the fingers of the left hand. Repeat CSF analysis revealed similar abnormalities to the previous analysis, and MRI showed a new small infarct in the right-sided motor area corresponding to the left fingers. He was treated with acyclovir (750 mg/day), prednisolone (1 mg/kg/day), and aspirin (100 mg/day). O₂-gas positron emission tomography (PET) revealed decreased cerebral blood flow (CBF) after acetazolamide injection and normal cerebral vascular reactivity (CVR). He was on continuous treatment with prednisolone and aspirin for 1 year. The muscle weakness of the fingers of the left hand and right-sided ophthalmoplegia improved, and magnetic resonance angiography revealed considerable decrease in the stenosis of the right middle cerebral artery. CBF before and after acetazolamide injection and CVR on O₂-gas PET also normalized. These results suggested that long-term treatment may prevent subsequent infarcts following herpes zoster ophthalmics.

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We report the case of a 19-year-old woman who had been suffering from general fatigue and exercise intolerance since 15 years old. At 18 years old, she experienced muscle weakness and myalgia of the calves. Six months later, she was admitted to our hospital. She showed muscle weakness of the neck and proximal limbs, and myalgia of the calves was prominent. Serum levels of creatine kinase (CK) and lactic acid were elevated, as was the level of lactic acid in cerebrospinal fluid. T₂-weighted and short-inversion-time inversion recovery (STIR) imaging of the lower limbs showed hyperintensity on bilateral gastrocnemius muscles, and the region revealed Gd enhancement. Based on histopathological findings from muscle and identification of a m.3271T>C point mutation, mitochondrial myopathy was diagnosed. Rest and administration of vitamins B₁ and B₂, coenzyme Q₁₀, and L-carnitine improved serum CK levels; however, exercise intolerance, myalgia, and lactic acidemia remained. Sodium pyruvate was then administered, and lactic acid levels, exercise intolerance, and findings on magnetic resonance imaging improved. Sodium pyruvate could prove effective in addressing both elevated serum lactic acid levels and exercise intolerance in mitochondrial disease.

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The patient was a 46-year-old woman having a history of multiple sclerosis (MS) for 14 years. She had been treated with interferon β-1b since 2001, but discontinued because of psychiatric problems in 2006. Thereafter relapses were observed 1–2 times a year, and EDSS became 2.5 to 6.5. In April 2012, relapse of MS was noticed and the patient received introduction of fingolimod (FTY) after methylprednisolone (mPSL) pulse therapy. Twenty days later, dysarthria and lower limb weakness were appeared. Brain MRI showed more than 20 several millimeter Gd enhanced lesions in periventricular white matter, juxta-cortical white matter, and cerebellum. Careful determination and observation are required upon the FTY administration into the MS with high frequency of relapse.

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We describe the case of a 29-year-old woman with recurrent aseptic meningitis that was caused by ergot agents. She miscarried at age 27, and the uterus constrictor methylergometrine was prescribed. Three days later, she developed aseptic meningitis and was hospitalized. Two years later, she again developed aseptic meningitis the day after she took ergotamine tartrate. In both events, her symptoms improved rapidly when the medication was stopped. The drug-induced lymphocyte stimulation test for methylergometrine yielded a value of 180%. Drug-induced meningitis is a rare form of recurrent aseptic meningitis. Many studies have reported cases of meningitis caused by non-steroidal anti-inflammatory drugs, but many other drugs can induce aseptic meningitis. To the best of our knowledge, this is the first case of aseptic meningitis induced by ergot agents.

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Creutzfeldt-Jakob disease (CJD) presents with rapidly progressive dementia associated with several symptoms including pyramidal, extrapyramidal, and cerebellar signs. In Japan, patients with PRNP gene mutations comprise 18.3% of CJD cases. In the present study, we report a 74-year-old man with a double mutation in the PRNP gene. He showed dysarthria, gait disturbance, and cognitive impairment. High signal intensity was observed in the bilateral cortex on brain MRI in diffusion-weighted images. There were high total Tau protein and 14-3-3 protein levels in the cerebrospinal fluid. We diagnosed him as having CJD clinically, and analyzed the PRNP gene, which revealed a V180I mutation and a M232R one, i.e., a compound heterozygous status. In our patient, the disease has very slowly progressive (total disease course, 37 months). The V180I and M232R mutations are specific mutations to Japanese CJD patients. For patients with a double PRNP gene mutation, only V180I and M232R have been known. Patients with a double mutation (V180I /M232R) in the PRNP gene might show an atypical disease course with a slow progression.

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A 30-year-old man, who was diagnosed with Behçet disease at 10 years of age, was hospitalized because of transient right hemiparesis after presenting with high fever and scrotal ulcers. Brain MRI revealed ischemic lesions in the area supplied by the anterior cerebral arteries. Analysis of cerebrospinal fluid (CSF) showed pleocytosis and a high interleukin-6 (IL-6) concentration (668 pg/ml). The patient was diagnosed with acute ischemic stroke associated with exacerbation of Behçet disease. After initiation of corticosteroid therapy, his clinical symptoms improved, and the CSF IL-6 concentration decreased. One year later, the patient developed high fever and scrotal ulcers after the onset of transient left upper limb plegia. Brain MRI showed an acute ischemic lesion in the right putamen, and CSF analysis showed an elevated IL-6 concentration (287 pg/ml). Brain CT angiography revealed stenosis of the left anterior cerebral artery and occlusion of the right anterior cerebral artery, which had been well visualized one year previously. Involvement of the intracranial cerebral arteries in Behçet disease is extremely rare. To the best of our knowledge, this is the first case report of a patient with recurrent symptomatic ischemic stroke associated with high fever and scrotal ulcers, which suggests exacerbation of Behçet disease.

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[in Japanese]

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