Multiple sclerosis is a neurodegenerative and inflammatory immune disorder in the central nervous system (CNS). Most patients show relapse-remitting clinical course. Some disease modifying medications for preventing the relapses including natalizumab (NTZ) are approved in Japan. Natalizumab (NTZ), a monoclonal antibody against α4 integrin present on the surface of lymphocytes, inhibits the binding of lymphocytes to vascular cell adhesion molecule-1 (VCAM-1) of endothelial cells and blocks the penetration of encephalitogenic T cells into the CNS. This review provides an update on the efficacy of an inhibition of relapses, adverse effects including progressive multifocal leukoencephalopathy, treatment after NTZ discontinuation, and body weight based treatment.

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Onabotulinum toxin type A treatment for post-stroke upper limb spasticity was investigated to contribute to establishing a standard dosage for Japanese patients. A total of 100 patients participated in the study. The outcome one month (33.6 ± 6.5 days) after the treatment was assessed by the Modified Ashworth Scale (MAS) to estimate the mean effect with a 10-unit injection and the standard dosage expected to improve MAS 1 degree. Average improvement of 263 muscles treated with a higher concentration of 10 units diluted in 0.2 ml was 0.207 ± 0.414 degrees, and that of 231 muscles treated with a lower concentration of 10 units in 0.4 ml was 0.149 ± 0.244 degrees without significant difference among diluted concentrations. To improve MAS 1 degree, 64.6 ± 31.1 units were required for the pectoralis major, 51.2 ± 21.3 units for the teres major, 111.7 ± 48.0 units for the biceps brachii, 51.6 ± 26.8 units for the brachioradialis, 54.1 ± 23.2 units for the brachialis, 34.4 ± 10.7 units for the pronator teres, 64.6 ± 27.9 units for the flexor carpi radialis, 62.4 ± 26.8 units for the flexor carpi ulnalis, 58.5 ± 31.1 units for the flexor digitorum profundus, 69.7 ± 35.1 units for the flexor digitorum superficialis, 24.6 ± 13.4 units for the flexor pollicis longus, and 15.6 ± 11.3 units for the adductor pollicis. Although the results shown here had no significant differences among concentrations, increasing the volume would disturb injection into small muscles, so we considered that a lower volume with a higher concentration should assure larger benefits. It is difficult to make effective injections into all spastic muscles within the officially permitted health insurance dosage of 240 units. Hence, it is advisable to increase the applicable upper limit based on safely achieved cumulative experience.

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Acute disseminated encephalomyelitis (ADEM) with an anti-galactocerebroside antibody is very rare. We report a case of 82-year-old man with ADEM associated with anti-galactocerebroside antibody in serum. He was admitted to our hospital after developing disturbed consciousness and respiratory failure. A cerebrospinal fluid examination disclosed an albuminocytologic dissociation and elevation of myelin basic protein. Magnetic resonance images revealed lesions in the medulla oblongata, pons, midbrain, bilateral cerebellar hemisphere and thalami. Initially, he was treated with methylprednisolone (1 g/day) for three days. His clinical symptoms improved. We found on 15^th hospital day that an anti-galactocerebroside antibody was positive in serum without serological evidence of Mycoplasma pneumoniae infection. This case can be diagnosed as ADEM associated with an anti-galactocerebroside antibody.

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We report 4 cases of elderly patients with abrupt onset of serious airway obstruction that is presumed to be due to indwelling nasogastric tube. 2 cases are patients of cerebral infarction and 2 cases are patients of Parkinson disease. The average number of days until NGTS is 17.8 days. In all cases, fiber-optic examination revealed complete loss of adduction in both vocal cords. Infection in the posterior cricoid region caused by ulcerative lesions at the upper end of the esophagus has been implicated as a pathophysiological mechanism of this syndrome, but it was not possible to confirm in the 4 cases. Because it is difficult to exactly diagnose with NGTS in clinical practice, there is a need to consider the inducing factor and response. Body mass index is very low in each of the 4 cases, ranging from 14.2 to 18.0, implying a severely malnourished or immunocompromised state, and may represent a high risk factor for this syndrome. Whenever this life-threatening syndrome is suspected, direct vocal cord examination and removal of the tube are recommended. In addition, the clinicians should not hesitate about doing intubation or tracheotomy in emergency.

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A 53-year-old male with a past medical history of hypertension and bipolar disorder gradually developed gait disturbance and cognitive dysfunction over half a year. His cranial MRI showed an area of hyperintensity in the right occipital lobe on T₂ weighted images and the surface of the lesion was enhanced along the sulci. We diagnosed his condition as amyloid-β-related angiitis (ABRA) based on brain biopsy. Repeated, frequent seizures resistant to several antiepileptic drugs (AEDs) occurred after the operation. Steroid therapy was effective and the symptoms, including the intractable seizures and MRI abnormalities dramatically improved. In contrast to the common wild type ε3/ε3 ApoE genotype, a majority of ABRA patients have ε4/ε4. However, in this case the rare ε4/ε2 type was detected. The ε4 allele is considered to promote Aβ deposition on the vessel wall, and ε2 is speculated to trigger vessel ruptures or vascular inflammation. Although seizure is not a common complication of brain biopsy, it occurred repeatedly and responded poorly to AEDs in this case. Surgical stress in this patient with ε2 probably induced the uncontrolled seizures. ApoE genotype may be an effective and low-invasive marker in case of suspected ABRA and in predicting the risks of the complication from brain biopsy.

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We report the case of a 55-year-old immunocompetent female with primary central nervous system lymphoma (PCNSL). Seven years previously, the patient presented with left facial dysesthesia, and a right thalamus lesion was revealed by brain MRI. Both her dysesthesia and the lesion disappeared spontaneously in six months. One year previously, she noted motor disturbance of the right limbs, and brain MRI revealed lesions in the bilateral basal ganglia and the left internal capsule which gradually increased in size. She was admitted to our hospital owing to the brain MRI findings of a white matter lesion in the left occipital lobe and bilateral optic neuritis. Previously, she had experienced two episodes of steroid-responsive uveitis in her left eye. An inflammatory disease such as multiple sclerosis was initially suspected because of the relapsing/remitting clinical course with a long time interval. Treatment with corticosteroids improved her clinical symptoms and decreased the size of the lesions, but the brain lesions and bilateral optic neuritis recurred within one month. At that time, the β₂ microglobulin level in the cerebrospinal fluid was high and the left occipital lobe lesions showed increased ¹⁸F-fluoro-deoxyglucose uptake in positron emission tomography and decreased Cho/NAA ratio in ¹H-MR spectroscopy. These findings suggested PCNSL. A brain biopsy confirmed the presence of diffuse large B cell lymphoma. Both uveitis and optic neuritis were considered to be caused by intraocular lymphoma associated with PCNSL. Although patients with PCNSL may experience temporary spontaneous remission, our present case suggests that the time interval from remission to relapse can be much longer than generally expected. We suggest that it is necessary to consider PCNSL and perform a brain biopsy on patients presenting with atypical clinical manifestations of an inflammatory disease, even in cases with a long clinical course.

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A 62-year-old woman presented at our hospital with a headache, cognitive decline, and fever that had persisted for 3 months. On admission, fever, headache, and mild cognitive dysfunction were all clearly evident, suggesting chronic meningoencephalitis. Laboratory examination showed mild neutrophilia as well as an increase in her erythrocyte sedimentation rate and serum C-reactive protein levels. MRI showed multiple small hyperintense lesions on T₂ weighted image and diffusion weighted image (DWI) in the cerebral cortex and white matter. Contrast-enhanced T₁ weighted image showed the abnormal pial enhancement along the cerebral sulci. Systemic evaluations for infectious organisms, autoantibodies, and malignant tumors were all negative. Her fever and neurological symptoms continued. As a result of worsening MRI findings, a brain biopsy was carried out. Neuropathological analysis revealed neutrophilic infiltration in the subarachnoid space and multinucleated giant cells. However, there was no vasculitis on the histological sections. This pathological finding was reminiscent of rheumatoid meningitis despite articular findings of rheumatoid arthritis, as well as rheumatoid factor (RF) and anti-CCP antibody tests being negative. After oral steroid therapy, her fever and inflammatory reactions by laboratory test diminished and her cognitive function improved remarkably.

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We report a 72-year-old woman with complex partial status epilepticus who showed recurrent episodes of complex visual hallucinations (CVH). Brain diffusion-weighted magnetic resonance images revealed gyriform cortical hyperintensity in the right parietal, occipital and temporal lobes, and brain magnetic resonance angiograhy revealed a hyperintensity in the right dilated middle cerebral artery during ictal period. Ictal N-isopropyl-p-(iodine-123)-iodoamphetamine single photon emission computed tomography (¹²³I-IMP-SPECT) with three-dimensional stereotactic surface projection (3D-SSP) 14 days after the onset of the first CVH revealed hyperperfusion in the right latero-inferior occipito-temporal region with relation to motion. CVH spontaneously subsided 17 days after the onset of the first CVH. CVH recurred one year after the first CVH. Ictal ¹²³I-IMP-SPECT with 3D-SSP revealed marked hyperperfusion in the right lateral parietal region probably with relation to face and figure hallucinations. Ictal scalp EEGs revealed rhythmic polyspikes at 12 Hz with high amplitude (100–200 μV) in bilateral posterior occipital and temporal region with the right side dominance for 20 seconds and more in several occasions. Interictal ¹²³I-IMP-SPECT with 3D-SSP 28 days after recurrence of CVH revealed marked hypoperfusion in the right lateral parietal region, and recovery of hypoperfusion in the right latero-inferior occipito-temporal region. These findings suggest that ictal CVH might be induced by the spread of epileptic discharges from the right parieto-occipito-temporal region with the old brain contusion (epileptogenic region) to the right latero-inferior occipito-temporal region and the right lateral parietal region (symptomatogenic regions).

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We report a 24-year-old Japanese man initially suspected to have Becker’s muscular dystrophy at the age of 6 years, because of a high level of creatine kinase in serum, though he discontinued visiting the hospital. At the age of 23, he was admitted to the hospital for severe dilated cardiomyopathy, and subsequently diagnosed with limb-girdle muscular dystrophy2M (LGMD2M) based on muscle biopsy and gene analysis. It was recently reported that some patients with fukutinopathy develop LGMD. Most of the cases reported in Japan showed mild skeletal muscle involvement despite serious cardiomyopathy, which may sometimes the initial symptom of the disease. Since muscular dystrophy patients can develop severe cardiac failure, irrespective of the severity of skeletal muscle involvement, regular examinations of cardiopulmonary function are necessary.

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A 56-year-old man who underwent a tooth extraction in the previous year presented with weakness of the right upper extremity. Brain CT and MRI scans showed subcortical hemorrhage in the left frontal lobe. His body temperature was 37.5°C. Blood examination revealed anemia, elevated levels of C-reactive protein, and a positive result for PR3-ANCA. Aggregatibacter segnis was identified in the incubated blood cultures, and transesophageal echocardiograms showed infectious growth in the anterior mitral leaflet. He was diagnosed with infectious endocarditis. After treatment with ceftriaxione, the clinical symptoms were improved. We concluded that infectious endocarditis caused cerebral hemorrhage and that the positive result for PR3-ANCA was a false positive. Infectious endocarditis can mimic ANCA-associated vasculitis. When ANCA-associated vasculitis is suspected, infectious endocarditis must be ruled out.

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[in Japanese]

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[in Japanese]

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