[Involvement of autonomic nervous system since middle age in elderly patient with giant axonal neuropathy caused by novel genetic mutation].

A 69-year-old man began to experience difficulty with walking at the age of 5 years and started use of a cane at around 13 years, then finally started using a wheelchair at 17 years old. A diagnosis of Charcot-Marie-Tooth disease was previously determined at another hospital, though neither peripheral nerve biopsy nor gene analysis was conducted. He visited our institution at the age of 54 years and irregular outpatient examinations were started, which indicated slowly progressive muscle weakness and sensory disturbance of the limbs, leading to a decline in activities of daily living. Gene analysis at 60 years old identified a novel homozygous missense mutation in the gigaxonin gene, c.1478A>C, p.E493A. Intellectual capacity was preserved and kinky hair was not present, though complications such as vocal cord paralysis, paralytic ileus, and dysarthria were noted starting at age 61. Based on these findings, the patient was diagnosed with a mild form of giant axonal neuropathy.

Immunotherapy-responsive Non-paraneoplastic Encephalitis with Antibodies against GAD, LGI1, and GABAA Receptor.

A 62-year-old man showed abnormal behavior. Brain magnetic resonance imaging revealed multifocal lesions on T2-weighted images. Initial screening revealed that he was seropositive for antibodies against glutamate decarboxylase, which usually indicates treatment resistance to autoimmune encephalitis (AE). Intensive immunosuppressive therapies, however, improved the neurological symptoms. In line with this, we also detected seropositivity for antibodies against leucine-rich glioma-inactivated 1 and gamma-aminobutyric acid A receptor (GABAAR). Brain imaging and treatment responsiveness suggested that antibodies against GABAAR were the main cause of symptoms. Furthermore, the patient showed the presence of triple anti-neural antibodies in the absence of malignancy and had a favorable clinical course.

[Improved instrumental activities of daily living in acquired savant syndrome patient after developing interest in drawing].

We performed examinations of a 73-year-old, right-handed man who developed herpes simplex encephalitis, with cognitive dysfunction including severe Wernicke's aphasia. Although he had never previously been interested in arts, use of a coloring book, recommended by his wife, led him to start drawing. A few years after the onset of brain disease, the patient began to copy pictures of landscapes. The lesion was in the left hemisphere and his work showed a strongly realistic tendency, thus we think that this case demonstrated characteristics of acquired savant syndrome. Along with the increase in drawing ability, instrumental activities of daily living (IADL), such as shopping and use of public transport, were also considerably improved in this patient. On the other hand, results of neuropsychological tests, such as the Standard Language Test of Aphasia, were not improved. We concluded that a sense of accomplishment from the drawing activity and communication with supporters might have led to improvement of IADL in this case.

LAC2 encoding a secreted laccase is involved in appressorial melanization and conidial pigmentation in Colletotrichum orbiculare.

Both Colletotrichum and Magnaporthe spp. develop appressoria pigmented with melanin, which is essential for fungal pathogenicity. 1,8-Dihydroxynaphthalene (1,8-DHN) is believed to be polymerized to yield melanin around the appresorial cell wall through the oxidative activity of laccases. However, no 1,8-DHN laccase has yet been identified in either Colletotrichum or Magnaporthe spp. Here, we report a laccase gene, LAC2, that is involved in the appressorial melanization of Colletotrichum orbiculare, which causes cucumber anthracnose. LAC2 encodes a protein with a signal peptide and has high homology to fungal laccases. The conidial color of lac2 mutants is distinct from that of the C. orbiculare wild type, and the mutants are nonpathogenic. Notably, the mutant appressoria are defective in melanization, and a host invasion assay showed that the appressoria are nonfunctional. LAC2 was induced during appressorial melanization. These results suggest that LAC2 oxidizes 1,8-DHN in the appressoria. The LAC2 homologues of other fungi located in the same phylogenetic clade as LAC2 fully complemented the lac2 mutants. Interestingly, a LAC2 homologue, located in a different clade, complemented the conidial pigmentation but not appressorial melanization of the mutants, suggesting that the LAC2 function in appressorial melanization might only be conserved in laccases of the LAC2 clade.

[Delayed posthypoxic leukoencephalopathy: case reports].

Delayed posthypoxic leukoencephalopathy (DPL) is a rare and less well known complication of hypoxic brain injury. Although it is well known that anoxic or hypoxic injury produces acute neurologic deficits, DPL typically manifests days to weeks after apparent recovery from an obtunded state, and patients with DPL demonstrate cognitive impairment, high brain dysfunction, parkinsonism, or psychosis. MRI findings of the brain demonstrate deep white matter abnormalities. We report 2 cases of DPL after hypoxia due to benzodiazepine overdose. Both of our patients had normal arylsulfatase A activity. Although DPL is seen in carbon monoxide poisoning, pseudodeficiency of arylsulfatase A activity, or drug overdose with heroin or morphine, there are only some previous studies of DPL caused by an overdose with benzodiazepine. It is unclear whether neurotoxicity from the drug in addition to hypoxia alone is involved, however, it is important to note that overdose of common drugs as sleeping medicine can cause DPL. Since DPL may often be misdiagnosed and be subjected to unnecessary treatments, it is also important to understand its unique clinical course and MRI findings. With prompt recognition of DPL, we expect that more cases of DPL caused by overdose with benzodiazepine will be diagnosed, because benzodiazepine overdoses are common.

Clinical features of late-onset poststroke seizures.

BACKGROUND: Compared to the patients with early-onset seizures (ES), those with late-onset seizures (LS) have a high risk of epilepsy that is a feared complication after stroke. However, few studies have described detailed clinical features of LS in Japanese patients. METHODS: To elucidate the clinical features of LS, a series of 448 stroke patients (cerebral infarction n = 286; cerebral hemorrhage n = 162) in our hospital were retrospectively examined in this study. Stroke location was determined by computed tomographic and/or magnetic resonance imaging scans. Lesion size was evaluated using the Alberta Stroke Program Early Computed Tomographic Score. We examined occurrence rate, onset time, and recurrence rate of LS. In addition, clinical features of the infarction of LS and non-LS group were compared on age, gender, laterality, location, and extent, respectively. RESULTS: LS occurred in 18 patients (4.0%). Of these, 17 experienced LS within 1.5 years after stroke. While epilepsy developed in none of the patients with ES, it developed in 33% of those with LS. Patients with cortical and a larger infarction involving the middle cerebral artery had at significantly greater risk of LS (P < .05). CONCLUSIONS: Patients with cortical and a larger infarction involving the middle cerebral artery should be carefully observed because of a high risk of LS.

A 51-year-old man with intramedullary spinal cord abscess having a patent foramen ovale.

The authors report a case of a 51-year-old man with intramedullary spinal cord abscess (ISCA) having a patent foramen ovale (PFO). He developed fever and tetraplegia after a recent dental treatment. MRI showed ISCA with longitudinal swelling from the upper cervical to the lumbar spinal cord. Cerebrospinal fluid (CSF) analysis indicated bacterial meningitis, and the culture of CSF revealed Streptococcus viridans. Transoesophageal echocardiography revealed the existence of a PFO. We suspected another possibility other than systemic bacteraemia, that paradoxical bacteric embolisation through PFO after the dental treatment caused ISCA. While several reports of brain abscess with PFO are available, this is the first report of ISCA with PFO.

Transforming growth factor-beta enhances connective tissue growth factor expression in L6 rat skeletal myotubes.

Transforming growth factor (TGF)-beta plays an important role in fibrosis of various organs and tissues. TGF-beta1 stimulates fibroblastic cells to form extracellular matrix (ECM), and regulates all critical events in wound healing. Connective tissue growth factor (CTGF), a TGF-beta-inducible molecule, has recently been reported to promote fibroblast proliferation, migration, adhesion and extracellular matrix formation, both in vivo and in vitro. In this study, we demonstrated that TGF-beta1 enhances CTGF mRNA and protein levels in L6 rat skeletal muscle myotubes. TGF-beta might, therefore, play a role in fibrosis of skeletal muscle by stimulating CTGF expression in the muscle tissue itself.

Subacute bulbar palsy as the initial sign of follicular thyroid cancer.

We report a 64-year-old woman with follicular thyroid cancer found by subacute bulbar palsy. Progressive bulbar palsy (PBP) was considered the most likely diagnosis, because no abnormal finding was detected on brain CT and blood test except for the decrease of free T4. An echogram of the thyroid revealed a small nodule which was shown to be class IIb by fine needle biopsy. However, 201Tl scintillation examination showed skull base metastasis. Follicular thyroid cancer sometimes seems to manifest as a distant metastasis with no clinically evident thyroid lesion. This case suggested the importance of a detailed survey for malignancy, when subacute bulbar palsy is seen.

Focal myositis in monozygotic twins.

Focal myositis is a rare disease with unknown etiology and a broad spectrum. Here, we present two cases in monozygotic twins who complained of recurrent pain of their calves and showed histological signs of inflammation and MRI image compatible with the diagnosis of focal myositis. The occurrence of twin cases not living in the same household suggests a genetic susceptibility to the disease.

Direct effects of tumor necrosis factor alpha (TNF-alpha) on L6 myotubes.

Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine responsible for a diverse range of signaling events within cells. We studied direct effects of TNF-alpha on skeletal muscle protein content. Incubation of the L6 myotubes with 1 to 10 U/ml of TNF-alpha resulted in a significant increase of total and myofibrillar protein contents as compared with the control. However, incubation with lower (0.001-0.1 U/ ml) or higher (100-300 U/ml) doses of TNF-alpha resulted in a decrease of protein content. These findings suggest that TNF-alpha may elicit both anabolic and catabolic effects on L6 myotubes in a dose dependent manner. The anabolic effect of TNF-alpha was mediated at least in part by mitogen activated protein kinase (MAPK), especially by an extracellular-regulated kinases (ERK). This divergent effect of TNF-alpha may be crucial to elucidate the complexity of TNF-alpha action on the skeletal muscle.

Human herpes virus 6 encephalitis in allopurinol-induced hypersensitivity syndrome.

Hypersensitivity syndrome is one of the most severe forms of drug eruption, and is characterized by a severe, potentially lethal, multiorgan involvement. Recently, reactivation of human herpesvirus 6 (HHV-6) has been suggested to be involved in this syndrome, although the exact role of HHV-6 remains elusive. In addition to exanthem subitum, neurological illnesses, such as infantile febrile illness without rash and encephalitis in immunocompromised patients have been attributed to HHV-6. A 51-year-old man developed a generalized erythematous eruption during treatment with allopurinol. Prednisolone improved his condition, but after the dose of prednisolone was reduced neurological abnormalities such as mental deterioration and positive meningeal signs developed. HHV-6 DNA in his blood by PCR analysis was positive. Furthermore, we detected HHV-6 DNA in the cerebrospinal fluid. The titers of anti-HHV-6-IgG increased during the course. His neurological symptoms gradually improved and no neurological sequelae were noted. Neurological abnormalities associated with hypersensitivity syndrome are very rare. However, the detection of HHV-6 DNA in the cerebrospinal fluid strongly indicates an involvement of reactivated HHV-6 in encephalitis.