[A case of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) with treatment-resistant status epilepticus that was effectively treated with lamotrigine].

A 16-year-old woman with MELAS developed fever and myoclonic epilepsy which improved with conventional anti-epileptic drugs. Since seizures recurred one month after successful treatment, the doses of phenobarbital, clonazepan, and valproate were increased. However, there was no improvement and status epilepticus continued. The addition of lamotrigine resulted in a decreased frequency and good control of seizures. This case is important, showing satisfactory results from the addition of lamotrigine for treatment-resistant status epilepticus.

Novel mutation in the replication focus targeting sequence domain of DNMT1 causes hereditary sensory and autonomic neuropathy IE.

DNMT1, encoding DNA methyltransferase 1 (Dnmt1), is a critical enzyme which is mainly responsible for conversion of unmethylated DNA into hemimethylated DNA. To date, two phenotypes produced by DNMT1 mutations have been reported, including hereditary sensory and autonomic neuropathy (HSAN) type IE with mutations in exon 20, and autosomal dominant cerebellar ataxia, deafness, and narcolepsy caused by mutations in exon 21. We report a sporadic case in a Japanese patient with loss of pain and vibration sense, chronic osteomyelitis, autonomic system dysfunctions, hearing loss, and mild dementia, but without definite cerebellar ataxia. Electrophysiological studies revealed absent sensory nerve action potential with nearly normal motor nerve conduction studies. Brain magnetic resonance imaging revealed mild diffuse cerebral and cerebellar atrophy. Using a next-generation sequencing system, 16 candidate genes were analyzed and a novel missense mutation, c.1706A>G (p.His569Arg), was identified in exon 21 of DNMT1. Our findings suggest that mutation in exon 21 of DNMT1 may also produce a HSAN phenotype. Because all reported mutations of DNMT1 are concentrated in exons 20 and 21, which encode the replication focus targeting sequence (RFTS) domain of Dnmt1, the RFTS domain could be a mutation hot spot.

[Anti-aquaporin-4 antibody autoimmune syndrome with disturbance of consciousness, respiratory failure, and ophthalmoplegia associated with extensive brain stem involvement with intractable hiccup and nausea as an initial manifestation. A case report].

A 45-year-old female was positive for anti-aquaporin-4 antibody with disturbance of consciousness, respiratory failure, and ophthalmoplegia associated with extensive brain stem involvement with intractable hiccup and nausea as an initial manifestation. Her level of consciousness and state of respiration worsened approximately one month later. There was no abnormality in the cerebrospinal fluid examination. A lesion was found in the medullary tegmentum on brain MRI. The patient received steroid pulse therapy and her level of consciousness improved the next day. However, her state of respiration worsened, and she had extensively clinical involvement of the brain stem. Her symptoms gradually improved with intravenous administration of prednisolone and intravenous immunoglobulin therapy (IVIg). The patient had almost completely recovered, but she relapsed with cervical myelitis extending over 3 vertebral segments approximately 10 months later. She underwent steroid pulse therapy, oral prednisolone, and IVIg again and improved.

[A spectrum of neurological diseases with anti-VGKC antibody].

Anti-VGKC antibody causing peripheral nerve hyperexcitability is already an established clinical entity. Recently, many patients with non-herpetic limbic encephalitis (NHLE) with anti-VGKC antibody have been reported. The characteristic clinical features are low serum Na+ concentration and good response to immunotherapy. Anti-VGK antibody positive NHLE is relatively frequent among immune-mediated NHLE. It is important to know that this disease is responsive to immunotherapy. Furthermore, anti-VGKC antibody is also positive in some intractable epilepsies. These findings suggest that anti-VGKC is correlated with hyperexcitability in both the peripheral and central nervous system and that the spectrum of anti-VGKC antibody syndrome is now expanding.

[Late onset epilepsy associated with migration disorder: a case report].

We reported a 57-year-old female patient recently suffering from frequent seizures such as motionless staring and oral automatism. Electroencephalograms showed spikes in the right sphenoidal derivation and magnetic resonance images revealed an abnormal region, most likely related with a migration disorder such as a focal cortical dysplasia. She was diagnosed as mesiotemporal lobe epilepsy associated with a migration disorder. Seizure disappeared after medication therapy was done. No previous literature has described such a case, thus this is the first report of an epilepsy associated with migration disorder newly onset in a patient older than 50 years old.

Mechanism of action of voltage-gated K+ channel antibodies in acquired neuromyotonia.

Acquired neuromyotonia (ANM) is associated with antibodies to voltage-gated K+ channels (VGKCs). ANM sera reduce the number of K+ currents in neuronal cell lines, but it is not clear how the antibodies act. Here, we show by using the NB-1 cell line that the reduction in K+ currents by IgG is independent of added complement. IgG Fc and Fab fragments from ANM sera had no effect, but three of four ANM F(ab')2 fragments significantly reduced K+ currents. Thus, cross-linking of the channels by divalent antibodies is likely to be an important mechanism in reducing K+ currents.

Isaacs' syndrome as a potassium channelopathy of the nerve.

Isaacs' syndrome (acquired neuromyotonia) is an antibody-mediated potassium channel disorder (channelopathy). The target channel proteins of the antigens are voltage-gated potassium channels (VGKCs), especially dendrotoxin-sensitive fast potassium channels. The suppression of voltage-gated outward K(+) current by antibodies induces hyperexcitability of the peripheral nerve. Patch clamp studies show that antibodies may not directly block the kinetics of VGKCs but may decrease channel density. Electrophysiological, pharmacological, and immunological findings indicate that the site of origin of spontaneous discharges is principally in the distal portion of the motor nerve and/or within the terminal arborization. The spectrum of potassium channelopathies is expanding. The existence of antibodies against VGKCs should be considered in patients who present with generalized nerve hyperexcitability of undetermined etiology.