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Biomedical subjects

Yushi Inoue

Publications and source records attributed to Yushi Inoue.

15 recordsLinked to original sources
PubMed2006

A Kv4.2 truncation mutation in a patient with temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) has a multifactorial etiology involving developmental, environmental, and genetic components. Here, we report a voltage-gated potassium channel gene mutation found in a TLE patient, namely a Kv4.2 truncation mutation. Kv4.2 channels, encoded by the KCND2 gene, mediate A currents in the brain. The identified mutation corresponds to an N587fsX1 amino acid change, predicted to produce a truncated Kv4.2 protein lacking the last 44 amino acids in the carboxyl terminal. Electrophysiological analysis indicates attenuated K+ current density in cells expressing this Kv4.2-N587fsX1 mutant channel, which is consistent with a model of aberrant neuronal excitability characteristic of TLE. Our observations, together with other lines of evidence, raise the intriguing possibility of a role for KCND2 in the etiology of TLE.

Action Potentials↗
PubMed2006

Postictal mania versus postictal psychosis: differences in clinical features, epileptogenic zone, and brain functional changes during postictal period.

PURPOSE: To clarify the differences between postictal mania (PIM) and postictal psychosis (PIP). METHODS: Five patients with PIM were compared to 17 patients with PIP, with respect to clinical, epileptological, electrophysiological, and neuroimaging features. PIM was distinguished from PIP by the symptoms observed in the postictal period based on the ICD-10 criteria. RESULTS: Postictal manic episodes lasted for a longer period than postictal psychotic episodes. Patients with PIM had more recurrent postictal episodes than patients with PIP. The age at onset of epilepsy in patients with PIM was older than that in patients with PIP. PIM was associated with frontal lobe and temporal lobe epilepsies, whereas PIP was associated with temporal lobe epilepsy. The estimated epileptogenic zone was on the language dominant side in PIM, whereas there was no predominant hemispheric laterality in PIP. Electroencephalography (EEG) performed during the early period of postictal manic and psychotic episodes showed decreased frequency of interictal epileptiform discharges in both PIM and PIP. Single-photon emission computed tomography (SPECT) during postictal manic and psychotic episodes showed increased perfusion in the temporal and/or frontal lobes in both PIM and PIP. Three patients with PIM showed increased perfusion during postictal episodes on bilateral or the language nondominant side, which were contralateral to the estimated epileptogenic zone, whereas three patients with PIP showed increased perfusion on the areas, which were ipsilateral to the estimated epileptogenic zone. CONCLUSIONS: PIM has a distinct position among the mental disorders observed in the postictal period.

Age of Onset↗
PubMed2005

Mutations in the NHLRC1 gene are the common cause for Lafora disease in the Japanese population.

Lafora disease (LD) is a rare autosomal recessive genetic disorder characterized by epilepsy, myoclonus, and progressive neurological deterioration. LD is caused by mutations in the EMP2A gene encoding a protein phosphatase. A second gene for LD, termed NHLRC1 and encoding a putative E3 ubiquitin ligase, was recently identified on chromosome 6p22. The LD is relatively common in southern Europe, the Middle East, and Southeast Asia. A few sporadic cases with typical LD phenotype have been reported from Japan; however, our earlier study failed to find EPM2A mutations in four Japanese families with LD. We recruited four new families from Japan and searched for mutations in EPM2A . All eight families were also screened for NHLRC1 mutations. We found five independent families having novel mutations in NHLRC1. Identified mutations include five missense mutations (p.I153M, p.C160R, p.W219R, p.D245N, and p.R253K) and a deletion mutation (c.897insA; p.S299fs13). We also found a family with a ten base pair deletion (c.822-832del10) in the coding region of EPM2A. In two families, no EPM2A or NHLRC1 mutation was found. Our study, in addition to documenting the genetic and molecular heterogeneity observed for LD, suggests that mutations in the NHLRC1 gene may be a common cause of LD in the Japanese population.

Amino Acid Sequence↗
PubMed2004

Mutations in EFHC1 cause juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is the most frequent cause of hereditary grand mal seizures. We previously mapped and narrowed a region associated with JME on chromosome 6p12-p11 (EJM1). Here, we describe a new gene in this region, EFHC1, which encodes a protein with an EF-hand motif. Mutation analyses identified five missense mutations in EFHC1 that cosegregated with epilepsy or EEG polyspike wave in affected members of six unrelated families with JME and did not occur in 382 control individuals. Overexpression of EFHC1 in mouse hippocampal primary culture neurons induced apoptosis that was significantly lowered by the mutations. Apoptosis was specifically suppressed by SNX-482, an antagonist of R-type voltage-dependent Ca(2+) channel (Ca(v)2.3). EFHC1 and Ca(v)2.3 immunomaterials overlapped in mouse brain, and EFHC1 coimmunoprecipitated with the Ca(v)2.3 C terminus. In patch-clamp analysis, EFHC1 specifically increased R-type Ca(2+) currents that were reversed by the mutations associated with JME.

Animals↗
PubMed2004

A nonsense mutation of the sodium channel gene SCN2A in a patient with intractable epilepsy and mental decline.

Mutations, exclusively missense, of voltage-gated sodium channel alpha subunit type 1 (SCN1A) and type 2 (SCN2A) genes were reported in patients with idiopathic epilepsy: generalized epilepsy with febrile seizures plus. Nonsense and frameshift mutations of SCN1A, by contrast, were identified in intractable epilepsy: severe myoclonic epilepsy in infancy (SMEI). Here we describe a first nonsense mutation of SCN2A in a patient with intractable epilepsy and severe mental decline. The phenotype is similar to SMEI but distinct because of partial epilepsy, delayed onset (1 year 7 months), and absence of temperature sensitivity. A mutational analysis revealed that the patient had a heterozygous de novo nonsense mutation R102X of SCN2A. Patch-clamp analysis of Na(v)1.2 wild-type channels and the R102X mutant protein coexpressed in human embryonic kidney 293 cells showed that the truncated mutant protein shifted the voltage dependence of inactivation of wild-type channels in the hyperpolarizing direction. Analysis of the subcellular localization of R102X truncated protein suggested that its dominant negative effect could arise from direct or indirect cytoskeletal interactions of the mutant protein. Haploinsufficiency of Na(v)1.2 protein is one plausible explanation for the pathology of this patient; however, our biophysical findings suggest that the R102X truncated protein exerts a dominant negative effect leading to the patient's intractable epilepsy.

Adult↗
PubMed2004

Visual reflex seizures induced by complex stimuli.

Visual reflex seizures induced by complex stimuli may be triggered by patterned and flashing displays that are now ubiquitous. The seizures may be clinically generalized, but unilateral and bilateral myoclonic attacks also may be triggered, especially in patients with juvenile myoclonic epilepsy, and recently, clearly focal reflex occipital lobe seizures have been described. Some seizure-triggering properties of video displays can be identified, such as perceived brightness, pattern, flicker frequency, and color. Knowledge of these is useful in planning individual treatment and in designing regulations for screen content of television broadcasts or for other video displays. Some subjects will also be sensitive to cognitive or action-programming activation, especially when playing video games, and this can increase the chance of seizure triggering. Nonspecific factors such as sleep deprivation, prolonged exposure, and drug or alcohol use also may play a role in reflex seizure occurrence.

Color↗
PubMed2004

Dystonic posturing associated with putaminal hyperperfusion depicted on subtraction SPECT.

PURPOSE: Dystonic posturing (DP) is one of the most reliable lateralizing indicators for temporal lobe epilepsy (TLE). We evaluated the ictal hyperperfusional areas in patients with DP by using ictal-interictal subtraction single-photon emission computed tomography (SPECT). METHODS: Ninety-seven patients were treated surgically for intractable TLE, and 39 patients underwent ictal and interictal SPECT studies with the same isotope. These patients were divided into three groups: group I with DP of the contralateral side extended to the epileptogenic focus, group II with elevated muscle tonus but without DP, and group III without DP or alteration of muscle tonus. Ictal, interictal SPECT and thin-slice magnetic resonance imaging (MRI) were overlaid by using the automatic multimodality registration program to construct ictal-interictal subtracted images of SPECT on MRI. RESULTS: Thirteen patients belonged to group I; 14, to group II; and 12, to group III. A statistically significant difference in hyperperfusion rate was observed in the putamen (10 patients in group I, three in group II and two in group III; p < 0.01) and mesial temporal lobe (10 patients in group I, seven in group II, and two in group III; p < 0.05) on the ipsilateral side of the epileptogenic focus. No statistically significant difference was observed for other ictal symptoms except ipsilateral upper-limb automatism (eight patients in group I, three in group II, and none in group III; p < 0.01). CONCLUSIONS: A strong correlation between DP and hyperperfusion in the putamen and mesial temporal lobe was demonstrated. Some patients showed a wide hyperperfusion area extending from the mesial temporal lobe to putamen, which may correspond to the propagation of epileptic discharges. Our results suggest a correlation between hyperperfusion of putamen and contralateral dystonic posturing.

Adolescent↗
PubMed2004

Epilepsy and driving in Japan.

PURPOSE: The driving regulations in Japan were amended in 2002, which lifted the absolute ban on driving by persons with epilepsy (PWE) and granted licenses to PWE after a 2-year seizure-free period. METHODS: To survey the effect of the new driving regulations, we sent questionnaires both to the driving authorities (DAs) and to doctors of the Japan Epilepsy Society (JES). RESULTS: Around 1,400 PWE legally obtained a driving license within 1 year after the amendment, licenses were rejected in 157, and 61 had the license withheld for <6 months. In most cases, the attending doctor assessed fitness for driving; 171 doctors responded to the questionnaire. One third of them commented on a positive change in attitude of PWE with respect to driving. Their main remarks included the need to shorten the seizure-free period to qualify for fitness to drive and the need for special guidelines for conditions such as rare seizure occurrence, recently diagnosed epilepsy, or reflex epilepsy. Problems of assessment identified included difficulty in deciding the time for reassessment, distress of PWE over cancellation of license, cost of the assessment, responsibility of the assessing doctors in case of seizure recurrence, and protection of privacy. They requested the DAs to promote publicity about the information and asked the JES to establish a guideline for assessing fitness to drive. CONCLUSIONS: The results highlighted the need for cooperation between the DAs and the JES for further amendment of the regulations as well as the importance of education for the public, patients, and professionals.

Accidents, Traffic↗
PubMed2004

[Treatment guidelines for adult epilepsy].

We reviewed the treatment strategies and choices of drugs for adult patients with epilepsy. As evidence from controlled studies for the older drugs is scarcely available from the literature, we added a clinical study performed in our hospital and an expert consensus study. Published randomized clinical studies revealed carbamazepine (CBZ) to be the treatment of choice, but provided little evidence for the differences in efficacy between phenytoin (PHT), valproate (VPA), phenobarbital (PB) and zonisamide (ZNS). The clinical study in our patients with intractable localization-related epilepsy indicated the superior efficacy of CBZ and PHT over VPA or ZNS. Sixty-nine experts converged on the opinion that monotherapy should be started with VPA for seizures of both idiopathic and symptomatic generalized epilepsy, and with CBZ for seizures of localization-related epilepsy. When the trials with 2-3 monotherapy failed, surgery should be considered for localization-related epilepsy. We proposed practical guidelines for treatment of patients with adult epilepsy, including rehabilitation and care for improvement of quality of life.

Adult↗
PubMed2003

Role of primary sensorimotor cortex and supplementary motor area in volitional swallowing: a movement-related cortical potential study.

We investigated the role of the cerebral cortex, particularly the face/tongue area of the primary sensorimotor (SMI) cortex (face/tongue) and supplementary motor area (SMA), in volitional swallowing by recording movement-related cortical potentials (MRCPs). MRCPs with swallowing and tongue protrusion were recorded from scalp electrodes in eight normal right-handed subjects and from implanted subdural electrodes in six epilepsy patients. The experiment by scalp EEG in normal subjects revealed that premovement Bereitschaftspotentials (BP) activity for swallowing was largest at the vertex and lateralized to either hemisphere in the central area. The experiment by epicortical EEG in patients confirmed that face/tongue SMI and SMA were commonly involved in swallowing and tongue protrusion with overlapping distribution and interindividual variability. BP amplitude showed no difference between swallowing and tongue movements, either at face/tongue SMI or at SMA, whereas postmovement potential (PMP) was significantly larger in tongue protrusion than in swallowing only at face/tongue SMI. BP occurred earlier in swallowing than in tongue protrusion. Comparison between face/tongue SMI and SMA did not show any difference with regard to BP and PMP amplitude or BP onset time in either task. The preparatory role of the cerebral cortex in swallowing was similar to that in tongue movement, except for earlier activation in swallowing. Postmovement processing of swallowing was lesser than that of tongue movement in face/tongue SMI; probably suggesting that the cerebral cortex does not play a significant role in postmovement processing of swallowing. SMA plays a supplementary role to face/tongue SMI both in swallowing and tongue movements.

Adult↗
PubMed2003

Nav1.1 channels with mutations of severe myoclonic epilepsy in infancy display attenuated currents.

Severe myoclonic epilepsy in infancy (SMEI) is characterized by intractable febrile and afebrile seizures, severe mental decline, and onset during the first year of life. Nonsense, frameshift, and missense mutations of SCN1A gene encoding the voltage-gated Na(+) channel alpha-subunit type I (Na(v)1.1) have been identified in patients with SMEI. Here, we performed whole-cell patch-clamp analyses on HEK293 cells expressing human Na(v)1.1 channels bearing SMEI nonsense and missense mutations. The mutant channels showed remarkably attenuated or barely detectable inward sodium currents. Our findings indicate that SMEI mutations lead to loss-of-function and may contribute to the development of SMEI phenotypes.

Cell Line↗
PubMed2003

Mutations of sodium channel alpha subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic-clonic seizures.

A group of infant onset epilepsies manifest very frequent generalized tonic-clonic seizures (GTC) intractable to medical therapy, which may or may not be accompanied by minor seizures such as myoclonic seizures, absences and partial seizures. They include severe myoclonic epilepsy in infancy (SMEI) and intractable childhood epilepsy with GTC (ICEGTC). They are commonly associated with fever-sensitivity, family history of seizure disorders and developmental decline after seizure onset. Mutations of the neuronal voltage-gated sodium channel alpha subunit type 1 gene (SCN1A) were recently reported in SMEI patients. To clarify the genotypic differences in this group of epilepsies, we searched for SCN1A abnormalities in 25 patients with SMEI and 10 with ICEGTC, together with the family members of 15 patients. Frameshift mutations in SCN1A were observed in four patients, nonsense mutations in five patients, missense mutations in 21 patients, other mutations in two patients and no mutation in five patients. SMEI patients showed nonsense mutations, frameshifts, or missense mutations, while ICEGTC patients showed only missense mutations. Study of both parents of 11 patients revealed that the mutations in these patients were de novo. However, two mothers had the same missense mutations as their ICEGTC children, and they had generalized epilepsy with febrile seizures plus. Here we suggest that SMEI and ICEGTC represent a continuum with minor phenotypic and genotypic differences.

Adolescent↗