[A case of idiopathic propriospinal myoclonus accompanied by giant somatosensory evoked potential].

A 41-year-old man visited our clinic because of headache with fever, suggestive of aseptic meningitis. His headache improved in a few days. His neurological examination showed positive jolt accentuation and myoclonus of the thoracoabdominal muscles extending to extremities upon patellar tapping. His myoclonus had been occurring spontaneously from early adolescence, especially in relaxed states such as drowsiness. The myoclonus was not triggered by tactile, auditory, or visual stimulation. Polymyography revealed that the myoclonus originated around the T4 spinal level and slowly propagated both upward and downward. These findings were indicative of spontaneous and reflex propriospinal myoclonus (PSM). No abnormalities were seen on brain and spinal MRI. Furthermore, the amplitude of the cortical component of the somatosensory evoked potential (SEP) after electrical stimulation of the tibial nerve was enlarged bilaterally. It was speculated that the ascending signals from the myoclonus generator at T4 to S1 may have modulated the excitability and inhibitory function of S1 in this patient. This report may be the first case of idiopathic PSM accompanied by giant SEP.

Atypical Familial Amyotrophic Lateral Sclerosis with Slowly Progressing Lower Extremities-predominant Late-onset Muscular Weakness and Atrophy.

Objective Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by the progressive loss of the upper and lower motor neurons that progresses to paralysis of almost all skeletal muscles of the extremities, bulbar, and respiratory system. Although most ALS cases are sporadic, about 10% are dominantly inherited. We herein report an atypical phenotype of familial ALS (fALS). To elucidate the phenotype-genotype correlation of this atypical phenotype of fALS, clinical and genetic investigations were performed. Methods and Patients Five sibling patients (three men, two women) from a Japanese family and one healthy sibling (a woman) were clinically interviewed and examined. Genetic analyses, including genome-wide linkage analyses and whole-exome sequencing, were performed using genomic DNA extracted from the peripheral blood samples of these siblings. Results The clinical features of fALS are characterized by slow progression (mean duration of the disease±standard deviation [SD]: 19.6±3.9 years) and lower extremities-predominant late-onset muscular weakness (mean onset of muscular weakness±SD: 52.8±2.6 years). Genetic analyses revealed novel heterozygous missense mutations of c.2668C>T, p.R890C in the PLEC gene and c.421G>C, p.V141L in the ST3GAL6 gene in all affected siblings. Conclusion A new atypical fALS family with a benign clinical course is herein reported. We identified two candidate gene mutations of PLEC and ST3GAL6 linked to this phenotype.

GCH1 mutations in dopa-responsive dystonia and Parkinson's disease.

Guanosine triphosphate cyclohydrolase I (GCH1) mutations are associated with increased risk for dopa-responsive dystonia (DRD) and Parkinson's disease (PD). Herein, we investigated the frequency of GCH1 mutations and clinical symptoms in patients with clinically diagnosed PD and DRD. We used the Sanger method to screen entire exons in 268 patients with PD and 26 patients with DRD, with the examinations of brain magnetic resonance imaging scans, striatal dopamine transporter scans, and [123I] metaiodobenzylguanidine (MIBG) myocardiac scintigraphy scans. We identified 15 patients with heterozygous GCH1 mutations from seven probands and five sporadic cases. The prevalence of GCH1 mutations in probands was different between PD [1.9% (5/268)] and DRD [26.9% (7/26)] (p value < 0.0001). The onset age tends to be different between PD and DRD patients: 35.4 ± 25.3 and 16.5 ± 13.6, respectively (average ± SD; p = 0.08). Most of the patients were women (14/15). Dystonia was common symptom, and dysautonomia and cognitive decline were uncommon in our PD and DRD. All patients presented mild parkinsonism or dystonia with excellent response to levodopa. Seven of seven DRD and three of five PD presented normal heart-to-mediastinum ratio on MIBG myocardial scintigraphy. Five of six DRD and three of four PD demonstrated normal densities of dopamine transporter. Our findings elucidated the clinical characteristics of PD and DRD patients due to GCH1 mutations. PD patients with GCH1 mutations also had different symptoms from those seen in typical PD. The patients with GCH1 mutations had heterogeneous clinical symptoms.

A case of cerebellar ataxia associated with VZV infection.

The varicella zoster virus (VZV) is a neurotropic virus that becomes latent in the sensory ganglia, but later causes various neurologic complications such as meningitis, encephalitis, myelitis, meningoencephalitis, cranial neuropathy, and peripheral neuropathy [1]. While acute cerebellitis is one of the most frequent acute cerebellar diseases associated with VZV in childhood, VZV rarely causes cerebellitis in adults, with or without skin manifestations, and only a few isolated cases of adult VZV cerebellitis have been reported. We report a case of acute cerebellitis associated with VZV infection after a herpetic rash in an 80-year-old male. Functional imaging of his cerebellum showed high blood perfusion during the acute stage of the disease, though perfusion decreased in the subacute stage.

[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).

[A Case of Anti-GQ1b Antibody Syndrome Associated with Pure Bilateral Adie's Pupils].

A 37 year-old Japanese male felt photophobia of both eyes one week following the onset of the common cold. His neurological examination revealed bilateral Adie's tonic pupils, no extraocular movement disorder, normal deep tendon reflexes, and no cerebellar signs. Based on markedly increased blood levels of anti-GQ1b IgG and anti-GT1a IgG antibodies, we diagnosed him as anti-GQ1b antibody syndrome. Bilateral Adie's tonic pupils were improved by IVIg drip infusion and methylprednisolone pulse therapy. This case suggests that we need to investigate anti ganglioside antibody when a patient presents with bilateral Adie's tonic pupils.

Bilateral optic neuropathy with bilateral putaminal lesions: a case report.

Bilateral optic neuropathy with bilateral putaminal lesions may be caused by methanol or cyanide poisoning or mitochondrial disorders including Leber hereditary optic neuropathy and Leigh syndrome. We report the case of a 34-year-old Japanese man who developed bilateral visual loss 5 days after the development of gastrointestinal symptoms. Magnetic resonance imaging of the brain on admission revealed high-intensity signal areas in the bilateral putamina on diffusion-weighted and T2-weighted images as well as a high-intensity signal area in the left middle cerebellar peduncle that had been identified 3 years previously. We diagnosed bilateral optic neuropathy with bilateral putaminal lesions caused by preceding infection-triggered demyelination. We administered methylprednisolone, but his vision did not recover.

Global aphasia without hemiparesis caused by a dural arteriovenous fistula.

A 61-year-old Japanese woman with chronic renal failure suddenly became silent at the end of hemodialysis. On a neurological examination, she was unable to respond to one-step commands, state the names of objects, repeat single words, read words aloud or write her name. Because she exhibited no paralysis of the extremities, we diagnosed her as having global aphasia without hemiparesis (GAWH). Cerebral angiography showed a dural arteriovenous fistula (AVF) in the left isolated transverse sinus with leptomeningeal venous drainage (Borden type 3, Lalwani grade 4). This case highlights dural AVF as an etiology of GAWH.

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.

[Selective impairment and a unique recovery of bilateral horizontal gaze and facial palsy in a discrete pontine lesion: a case report].

A 77-year-old woman with bilateral horizontal gaze palsy, right hemifacial weakness and incomplete quadriplegia was transferred to our hospital. Brain magnetic resonance imaging on the first day revealed a slit-like signal deficit of the basilar artery and an abnormal signal area at the dorsal midline portion of the lower pons. Quadriplegia fluctuated in several days after admission, then disappeared finally. In spite of the recovery of quadriplegia, bilateral facial weakness appeared on Day 14 after the onset. Concerning the impairment of extraocular movements, bilateral adduction restored gradually followed by improvement of the right abduction. The clinical course suggested the involvement of bilateral medial longitudinal fasciculus (MLF) and abducens nuclei (or fibers) as the etiology of gaze palsy. Although bilateral MLF sign recovered within 3 weeks, and the abductor palsy of both eyes was persisted in mild degree. As imaging analysis did not always show the causative lesion, which correlated with the rapidly alternating signs in the patient, and careful neurological observation was therefore useful in the management of patients with brainstem dysfunction.

[Successful treatment of methicillin-resistant staphylococcus aureus meningitis by intrathecal injection of vancomycin].

A 70-year-old Japanese man developed fever, headache, and lumbago, presumably due to an epidural abscess caused by methicillin-resistant Staphylococcus aureus (MRSA) in the L5-S2 region. On the night of admission to our hospital, he showed disorientation to places and abnormal eating behavior, indicating a complication of MRSA meningitis. Cerebrospinal fluid (CSF) examination confirmed this diagnosis. Although he was treated with venous infusion of vancomycin and meropenem, the CSF culture remained positive for MRSA even a week after the treatment, and Gram-positive cocci were also seen in the CSF. An intrathecal injection of vancomycin (10mg/day) was subsequently added, which resulted in absence of the organism on Gram-stained CSF smear and CSF culture a week later. His condition improved without any adverse effects. Vancomycin cannot freely penetrate the blood-brain barrier (BBB); therefore, when administered intravenously, its concentration in the CSF is insufficient. Therefore, intrathecal injection of vancomycin is necessary to achieve the desired bacteriocidal level in the CSF. Thus, intrathecal administration of vancomycin seems a very effective and safe treatment for MRSA meningitis.

Familial Parkinsonism with digenic parkin and PINK1 mutations.

To clarify the genetic correlation between parkin and PINK1, we screened for PINK1 mutations in 175 parkinsonism patients with parkin mutations. We detected two sibling pairs and one sporadic patient carrying both parkin and PINK1 mutations. The age at onset of Parkinsonism of patients with the digenic mutations was lower than that of patients with the same parkin mutation alone. In addition, two of three patients carrying both parkin and PINK1 mutations had schizophrenia. These findings indicate that PINK1 mutation might modify parkin mutation-positive Parkinsonism, and PINK1 mutations might be associated with psychiatric disorders.

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.

[A case of Aspergillus brain abscess presenting angular gyrus syndrome].

A 45-year-old man had been treated for chronic alcoholism and he had fever in September 2000. He was diagnosed as lung aspergillosis from chest X-ray findings, leukocytosis, elevated CRP, and beta-D-glucan. Administration of fluconazole was started and his lung lesion subsided. But, generalized clonic tonic convulsion developed and the brain abscess in the left parietal lobe was found by CT. Therefore we made the diagnosis of brain abscess followed by lung aspergillosis. He also showed angular gyrus syndrome. Its capsule was thick and localized in the left parietal lobe. The patient had the surgical resection in August, 2001. Aspergillus hyphae and infiltration of inflammatory cells were seen in the brain sample, therefore the diagnosis of aspergillosis brain abscess was established. Angular gyrus syndrome was ameliorated after the operation.

[An autopsy case of polymyositis with exacerbation of chronic myocarditis].

A 38-year-old man had suffered from general fatigue, mild weakness of proximal muscles, and dry cough in November, 2000. Serum levels of muscle enzymes were elevated. Computed tomography of the chest revealed reticular appearance in the bilateral dorsal lung areas. He did not show any improvement, therefore he was referred to our hospital in April, 2001. He was diagnosed as mild polymyositis with mild interstitial pneumonia. He was treated intravenously with methylprednisolone pulse therapy. During the pulse therapy serum level of creatine kinase was decreased, but he died because of acute pump failure of the heart. The cause of the heart failure could be an exacerbation of chronic myocarditis associated with polymyositis and it was confirmed by autopsy findings. When a patient with mild polymyositis complains of general fatigue, myocarditis should be carefully evaluated because of the high risk of death.

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.