Treatment of patients with clinically isolated syndrome (CIS) with disease modifying drugs including interferon β delays conversion to clinically definite multiple sclerosis (MS). However, CIS patients do not necessarily develop MS even after 20 years. Brain MRI lesions were required for CIS patients to include in clinical trials such as CHAMPS study and BENEFIT study. CIS patients with brain MRI lesions compatible to MS were considered as high risk to convert to MS in western countries. Previously we reported that asymptomatic enhancing brain lesions (AEBLs) were found in 9/23 (39.1%) of MS patients who had suffered at least one relapse in the preceding year or two relapses in the preceding 2 years, and the number of AEBLs per scan was 0.37, suggesting low disease activity of Japanese MS patients. We examined brain MRI findings in Japanese CIS patients and compared with those of Japanese MS patients at the first presentation.
We reviewed brain MRI of 23 CIS visited our clinic from December 2007 to October 2010 who fulfilled the criteria proposed by Kappos et al. (2006) and Dalton et al (2002). Thirty two clinically definite MS (CDMS) patients fulfilled the first McDonald criteria (two or more attacks and objective clinical evidence of two or more lesions) proposed by Polman et al. (2005). Patients with neuromyelitis optica (NMO) and patients with NMO spectrum proposed by Wingerchuk et al. (2006) and Wingerchuk et al. (2007), respectively, were excluded. Patients with anti-aquaporin4 antibodies or with contiguous spinal cord lesion extending over three vertebral segments on MRI were also excluded.
We could not obtain MRI of 11 patients with CDMS because of very long disease course, and 2 CIS and 13 CDMS patients had not been examined with MRI. So we examined 21 CIS and 8 CDMS patients at the first presentation using Paty criteria and Barkhof criteria. Eleven CIS patients did not meet any of the Barkhof criteria. Seven and 3 CIS patients met one and two of Barkhof criteria, respectively. No CIS patients showed fulfilled more than 3 of Barkhof criteria. Seven of eight CDMS patients at the first presentation showed more than one of the Barkhof criteria, however, only one CDMS patient at the onset fulfilled more than 3 of the Barkhof criteria. Japanese CIS patients seemed to show less brain lesions than those in western countries.

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We conducted a questionnaire survey on 7,500 members of the Societas Neurologica Japonica regarding the carry-over from pediatric to adult epilepsy care. The response rate was 16.9%. Analysis of the responses showed that 46% of the neurologists were aware of the term "carry-over" in epilepsy care, and 78% felt difficulties with epilepsy care in general. The most common reasons included "not familiar with interpreting EEG" and "not familiar with the laws, regulations and medical and welfare systems specific to epilepsy".
Among the neurologists who felt difficulties when accepting epilepsy patients aged 20 years or older referred from the pediatric department, 68% had experienced accepting these patients. The two major reasons for feeling difficulties when accepting these patients were "difficult to have good understanding of the disease course from infancy" and "not familiar with the epilepsy syndrome specific to infancy".
The above findings highlight the importance of recognizing the existence of the issue of carry-over in adult epilepsy care and its significance, and to resolve the factors that hinder the transition of care. To achieve this goal, joint activities of the Japanese Society of Child Neurology and the Japan Epilepsy Society in collaboration with the Societas Neurologica Japonica, the Japanese Society of Psychiatry and Neurology, and the Japan Neurosurgical Society are critical.

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A 75-year-old man was admitted to our hospital with progressive weakness in the lower extremities for 7 months. Immunoelectrophoresis of serum detected IgA λ type M protein and bone marrow examination detected an increase in monoclonal plasma cells, thus leading to a diagnosis of IgA λ type multiple myeloma. Subsequent muscular CT scan showed severe fatty infiltration of vastus lateralis muscles, and histopathological examinations of biopsied muscle specimens an abundance of abnormal "ring-fiber-like" appearance, positive staining by Congo red and the presence of anti-λ light chain antibody. This led to a diagnosis of amyloid myopathy. No depositions were seen in rectal mucosa, cardiac muscle, or sural nerve. The results of double immunohistochemical staining using anti-dystrophin antibody and anti-λ light chain antibody suggested the possibility of direct injury by amyloid to muscle fibers. The case presented here was thus amyloidosis confirmed by deposition of amyloid only in muscles. In conclusion, when amyloidosis is suspected and there is evidence of muscle injury, muscle biopsy should be performed.

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We report a 38-year-old man with vaccine associated paralytic poliomyelitis (VAPP) which showed unusual biphasic worsening. The patient developed mild paresis of left upper and right lower extremities, five weeks after the oral poliovirus vaccination of patient's son and two weeks after the intramuscular injection of mumps/varicella vaccine in the left triceps muscle for himself. Needle electromyography (EMG) of his left arm and right leg was not remarkable, and the weakness recovered almost completely in three weeks. However, four weeks after the needle EMG, severe weakness and muscle atrophy of the four extremities, accentuated at the left arm and right leg, developed again. Cervical MRI showed gadolinium-enhanced, T₂ high-signal intensity area in the left C4-C6 anterior horn, most prominent at the height of C5 spine. Significant elevation of serum anti-poliomyelitis type 2 neutralizing antibody confirmed the diagnosis of VAPP. Immunomodulatory treatment, intravenous immunoglobulin (IVIg), did not improve weakness. We consider that the second clinical worsening of this patient was provoked by the needle EMG performed just after the first exacerbation, which injured the skeletal muscles and might have enhanced the retrograde transport of poliovirus via neural pathway.

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We report an autopsy case of a 74-year-old man with late onset Charcot-Marie-Tooth disease type 1A (CMT1A) diagnosed by genetic screening, later associated with amyotrophic lateral sclerosis (ALS). At the age of 70 years, the patient was admitted to our hospital because of progressive weakness and dysesthesia in the right upper limb. In the early stages of the illness, he was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and transient improvement was achieved with intravenous immunoglobulin. However, the symptoms progressively worsened and became refractory. Gene analysis revealed PMP22 gene duplication, which confirmed CMT1A. On sural nerve biopsy, severe demyelinating neuropathy and abundant onion-bulb formations with endoneurial infiltration of inflammatory cells were observed. Thereafter, pseudo-bulbar palsy and respiratory muscle weakness developed insidiously and progressed rapidly along with muscle weakness in the limbs and trunk. The patient died about four years after the onset of this disease. Postmortem examination showed moderate neuronal cell loss, Bunina bodies, and TDP-43-positive inclusions in the anterior horn cells. The spinal cord revealed axonal loss and extensive macrophage permeation in the corticospinal tracts. On the basis of these findings, the final neuropathological diagnosis was ALS. This is the first report of an autopsy case of CMT1A complicated with ALS. We here discuss the significant clinical and neuropathological findings of this case.

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We report a Japanese breath-hold diver (Ama) who presented neurological disorders after diving. He repeated diving into 25-30 meters depth in the sea for 6 hours. After diving, he felt dizziness and unsteady gait. Neurological examination showed left quadrant hemianopia, bilateral limb ataxia and ataxic gait. Head CT revealed gas bubbles in the left parietal lobe. In CT scan on 3 days after onset, gas bubbles disappeared and low density areas were observed in the bilateral parietal lobes. Brain imaging (DWI, T₂WI and FLAIR) demonstrated high intensity in the parieto-occipital lobes. Neither pulmonary barotrauma nor intracardiac shunt was detected. He was diagnosed as having neurological decompression illness and therefore underwent hyperbaric oxygen therapy. The pathogenesis of this case was considered to be microbubbles induced by decompression. The present case suggests that repetitive rapid surfacing from the deep sea causes neurological decompression illness even in the breath-hold diver.

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A 28-year-old man admitted to our hospital because of severe neck pain, headache, fever and vomiting. He was alert and had no neurological deficit except for nuchal stiffness. Cerebrospinal fluid (CSF) examination showed elevated mononuclear cell counts (68/mm³) and protein levels (300mg/dl). He was diagnosed as having aseptic meningitis and was thereby treated. Two days later, he manifested seizure and on the next day, severe cerebral hemorrhage occurred in the left parietal lobe and decompression surgery was performed. Cerebral venous thrombosis was strongly indicated by operative findings, cerebral angiography and retrospective assessment of MRI images. Genetic testing revealed a novel mutation (p.Cys449Tyr) combined by Protein S Tokushima mutation (p.Lys196Glu) which is frequently observed in Japanese. Possibility of CVT should be noted, even when a patient exhibits clinical symptoms and CSF findings compatible with a diagnosis of aseptic meningitis.

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We present a 39-year-old woman with transient global amnesia (TGA) who showed sudden onset amnesia immediately following sexual intercourse after taking a bath. Her amnesia resolved within 6 hours. Three-Tesla (3T) diffusion weighted magnetic resonance imaging (DWI) taken 80 hours after the onset revealed hyperintense spots in the CA1 subfields of the bilateral hippocampi. No abnormalities were noted in 3T DWI, T₂ weighted imaging (T₂ WI) and fluid attenuated inversion recovery (FLAIR) at 3 weeks after the onset. She had no cardiovascular diseases. Magnetic resonance venography (MRV) revealed hypoplasia of the right transverse sinus and stenosis of the bilateral brachiocephalic veins. Ultrasound sonographic studies revealed a prolonged retrograde flow component of the right internal jugular vein during a Valsalva maneuver.
The vast majority of TGA attacks occur between the ages of 50 and 80, and very rarely under the age of 40 years, which is mostly not exposed to vascular risks. We therefore speculate that in conjunction with a decreased vascular beds from the brain, a Valsalva-like maneuver might have precipitated cerebral venous ischemia in the bilateral hippocampi, which are the most vulnerable to ischemic insults.

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A 53-year-old man presented mild, but gradually worsening, distal-dominant upper bilateral limbs weakness and muscle cramp in both legs from the age of 30. He had no obvious muscle atrophy during the course of the disease. Muscle biopsy of the right lateral vastus muscle showed myopathic changes with round or helical hyaline inclusions in eosinophilic on H&E staining and dark green on modified Gomori trichrome. There were also non-rimmed vacuoles. NADH-TR showed lack of enzymic activity in areas corresponding to the inclusions. Immunohistochemistry demonstrated abnormal accumulation of desmin and myotilin in fibers with inclusions. Given these pathological findings, he was diagnosed with myofibrillar myopathy (MFM). Because MFM is genetically heterogeneous, its clinical manifestations are reported as variable. While MFM patients are sometimes reported to develop serious conditions such as severe weakness, cardiomyopathy or respiratory failure, which require a pacemaker or mechanical ventilator, our case only had mild distal dominant limb weakness and muscle cramps. Our patient suggests that we must consider MFM as a differential diagnosis in adult onset distal myopathies.

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A 94-year-old woman was admitted to our hospital because of altered mental status and cerebellar ataxia of left upper and lower extremities. A brain CT scan revealed a right cerebellar hemorrhage approximately 15cc. Plasma brain natriuretic peptide (BNP) value on admission was 1,064.6pg/ml. Twelve-lead ECG revealed negative T-wave in V3-V5. Transthoracic echocardiology confirmed an ejection fraction of 35%, and left ventricular apical akinesia and basal hyperkinesis were seen. Plasma BNP value was dramatically declined in the subacute phase of cerebellar hemorrhage. On the 14th day, echocardiography showed completely improvement of the left ventricular wall abnormalities. Therefore, we diagnosed having as a Tako-tsubo cardiomyopathy. Tako-tsubo cardiomyopathy is a rare complication of acute intracerebral hemorrhage. In the present case, plasma BNP was effective as a screening marker of Tako-tsubo cardiomyopathy and serial measurement of BNP was made helpful to know cardiac status.

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A 33-year-old man was admitted to our hospital because of right exophthalmos, diplopia and left neck pain. Neurological examination revealed lateral and inferior disturbance of his right eye movement and the meningeal irritation sign. Cerebrospinal fluid showed elevated polynuclear cells. Enhanced CT and MRI revealed thrombophlebitis of the left internal jugular vein and bilateral cavernous sinuses. On the basis of these findings, he was diagnosed as having Lemierre syndrome associated with cavernous sinus thrombophlebitis and bacterial meningitis. After administration of antibiotics, his symptoms disappeared and the data of laboratory analyses also improved. However, after his discharge, he was required re-antibiotics therapy because of septic embolus- induced multiple lung abscesses. Lemierre syndrome is characterized by disseminated abscesses and thrombophlebitis of the internal jugular vein after infection of the oropharynx. Because Lemierre syndrome is potentially life-threatening, early diagnosis and initiation of appropriate therapy are important.

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[in Japanese]

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[in Japanese]

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