[Benign Outcome of Cochlear Implantation in a Patient with Superficial Siderosis].

We report the case of a 38-year-old man with gait disorder and hearing loss. The patient had developed gait disorder due to a cervical meningioma since 4 year-old disappeared for 15 years after the surgical removal of the meningioma. However, at the age of 21 year-old, the gait disorder reappeared and worsened progressively. Sensorineural hearing loss (SNHL) and epileptic seizures developed during the disease course, and he was diagnosed with superficial siderosis (SS). When he was 37 years old, he experienced sudden-onset of right-side hearing impairment and was considered a candidate for cochlear implantation (CI) at the otorhinolaryngology clinic of the nearby University Hospital. He underwent CI in November 2014. Eight months after the operation, his right side hearing improved although ataxia, hearing loss, and pyramidal sign persisted. At the long term follow-up of 29 months after CI, his hearing remained at the improved level. Thus, CI may be an effective long-term treatment for SNHL in patients with SS and could prevent the progression of his hearing loss. (Received February 1, 2017; Accepted August 23, 2017; Published January 1, 2018).

Confirmation of the efficacy of vitamin B6 supplementation for McArdle disease by follow-up muscle biopsy.

No effective treatment for McArdle disease exists.We report a Japanese patient with McArdle disease who was treated with vitamin B(6) supplementation (60-90 mg/day). After treatment, increased muscle phosphorylase activity was confirmed by follow-up muscle biopsy (3.8 times higher than pretreatment levels). Increased lactate levels were seen on the forearm exercise test, and regular work activities could be resumed. Vitamin B(6) supplementation can enhance residual phosphorylase activity and improve insufficient anaerobic glycolysis of skeletal muscle.

LAMP-2 positive vacuolar myopathy with dilated cardiomyopathy.

We report a 46-year-old male patient with late-onset vacuolar myopathy and dilated cardiomyopathy. Acid maltase activity of the muscle was normal, but the biopsied muscle specimen stained for lysosome-associated membrane protein-2 (LAMP-2), which has recently been reported to be deficient in muscles of patients with Danon disease. The clinical features of the patient are distinct from X-linked myopathy with excessive autophagy, infantile autophagic vacuolar myopathy and autophagic vacuolar myopathy with late-onset and multiorgan involvement (Kaneda).

Familial amyotrophic lateral sclerosis with His46Arg mutation in Cu/Zn superoxide dismutase presenting characteristic clinical features and Lewy body-like hyaline inclusions.

We evaluated the characteristic clinical features of one family of familial amyotrophic sclerosis (FALS) with a His46Arg mutation in the enzyme Cu/Zn superoxide dismutase (SOD1). Codon 46 encodes the binding site for copper and the His46Arg mutation may result in decreased copper binding and copper toxicity. The disease duration of this family was 17.8+/-13.2 years (mean+/-S.D.) with the age at onset being 42.9+/-4.7 years old (mean+/-S.D.). The initial sign was distal weakness of the unilateral lower limb, extending to the other lower limb. An autopsy was performed on a 62-year-old female member of the family who had the mutation. Her disease duration was 23 years, and she died of tonsillar herniation caused by metastasis of colon cancer in the cerebellum. Neuropathological findings showed marked loss of large anterior horn cells and very mild degeneration of corticospinal tracts as well as posterior columns. The number of nuclei of Clark's column was reduced. Lewy body-like hyaline inclusion bodies (LBHIs) were frequently seen in the remaining anterior horn cells. Astrocytic hyaline inclusions (Ast-HIs) were also seen. This is the first autopsy report of FALS with a His46Arg mutation presenting neuronal LBHIs and Ast-HIs. The formation of LBHIs and Ast-HIs may be dependent on the phenotype of the preferential lower motor neuron involvement in FALS with a SOD mutation and long disease duration.

Correlation of emmprin expression in vascular endothelial cells with blood-brain-barrier function: a study using magnetic resonance imaging enhanced by Gd-DTPA and immunohistochemistry in brain tumors.

In a previous study, we demonstrated that the expression levels in tumor cells of emmprin (CD147) correlated with the grade of astrocytic tumors. Also, we found that emmprin was expressed in vascular endothelial cells of the non-neoplastic brain and hypothesized that emmprin expression could be associated with normal blood-brain-barrier (BBB) function of vascular endothelial cells. In this study, this possibility was examined in non-neoplastic brain, glioma and metastatic carcinoma tissues by comparing emmprin immunohistochemistry with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement of magnetic resonance imaging (MRI), which is a clinical indicator of the BBB function. This study included 10 cases of non-neoplastic brain tissues, 7 of metastatic carcinoma, 7 of diffuse astrocytoma, 4 of anaplastic astrocytoma and 13 of glioblastoma multiforme. In all the cases, MRI with administration of Gd-DTPA was performed. The lesions were resected using the microdissection method with the help of ultrasonography and a neuronavigator. The tissues from Gd-DTPA-enhanced or non-enhanced areas were processed into frozen sections and subjected to immunohistochemistry with anti-emmprin antibody. The expression of emmprin in brain vascular endothelial cells inversely correlated with Gd-DTPA-enhancement of MRI: emmprin was positive in tissues not enhanced by Gd-DTPA and was negative in DTPA-enhanced tissues. Since BBB function presumably remains unimpaired in regions in which MR images are not Gd-DTPA-enhanced, emmprin expression appears to be associated with unimpaired BBB function. This is the first report to demonstrate a possible correlation between emmprin expression and BBB function in humans.

[Chronic and predominantly sensory polyneuropathy in Toroku Valley where a mining company produced arsenic].

We report 9 patients (5 males, 4 females, ages 63-77) with chronic polyneuropathy. They were exposed to arsenic for about 15-40 years in Toroku Valley, Takachiho-Town, Miyazaki Prefecture, Japan, where a mining company produced arsenic from 1920-1962. Predominantly sensory polyneuropathy was the most significant neurological finding. In 5 of them, superficial and deep sensation was equally affected over the entire body, including head, face, and mucous membranes of the mouth. The corneal reflexes were absent or sluggish. Pin-prick and light-touch perception was absent in their hands and legs. Another sensory disorder such as glove and stocking-type was seen in 4 of them. All 9 patients were comfortable with extremely hot water in their beverages, their baths, and their wash basins compared with controls. But these patients felt that their temperature sensation was normal. Motor involvement was minimal. Although motor-nerve conduction velocities were normal or reduced minimally, sensory-nerve conduction velocities were moderately reduced. Sural-nerve biopsy revealed reduction of both small myelinated and unmyelinated fibers, which occurs with axonal degeneration of peripheral nerves. Other main symptoms and signs were tension-type headaches, non-painful tonic spasms of limbs, and losses or significantly decreased sensations of taste and smell. Dantrolene-sodium was effective for the treatment of their non-painful tonic spasms of limbs. As for the general medical condition of these patients, all of them had suffered from chronic bronchitis and skin eruption during childhood or in their early life or in their young adulthood when the mine was producing arsenic. At the time of this study only four of them suffered from chronic bronchitis and none of them had skin eruptions or discoloration of the skin, 37 years after closure of the mine. These 9 patients were diagnosed as having chronic arsenic poisoning and arsenic polyneuropathy. The multiplicity of symptoms found in these patients--anosmia, ageusia, chronic bronchitis, tension-type headaches, and non-painful tonic spasms of limbs--differs from the symptoms previously reported cases with arsenic poisoning. This may be due to combined overexposure to environmentally hazardous arsenic by effluent gas, dust, and drinking water in Toroku Valley. As concerns the sensory disorders described above, it is necessary to investigate sensory conduction pathways, including cerebral sensory cortex, spinal cord, and skin sensory receptors such as Pacini corpuscles, and Meissner corpuscles. Unfortunately, no information has been obtained about this problem because there were no autopsy cases.