Functional recoveries of patients with branch atheromatous disease after rehabilitation: Comparison with other types of cerebral infarction and importance of stratification by clinical categories.

BACKGROUND: Functional recoveries after rehabilitation of patients with branch atheromatous disease (BAD) have not been well investigated, however, clinical category of cerebral infarction including BAD itself could be a potential predictive factor for functional outcome. OBJECTIVE: To describe characteristics of functional recoveries of patients with BAD through comparison with other types of cerebral infarction. METHODS: We retrospectively compared outcomes of patients with BAD (N = 222), cardioembolic cerebral infarction (CE: N = 177) and atherothrombotic cerebral infarction (AT: N = 219) by using functional independence measure (FIM) and FIM effectiveness (the proportion of potential for improvement achieved). RESULTS: Univariate analysis showed that FIM on discharge was comparable among three types of cerebral infarction, but that FIM effectiveness in patients with BAD was significantly higher than those with CE or AT. Stratified analysis revealed higher FIM effectiveness in patients with BAD compared to patients with CE or AT, if they were male, younger (≤72 years) or had supratentorial brain lesions. Multiple regression analysis demonstrated that location of the brain lesion (supratentorial vs infratentorial) and gender (male vs female) were significantly associated with FIM on discharge, and that cognitive function on admission as well as gender were significantly associated with FIM effectiveness in patients with BAD, but not in patients with CE or AT. CONCLUSIONS: Outcomes after rehabilitation of patients with BAD may be characterized by better functional improvement, especially if patients are male, relatively younger or with supratentorial lesions. The impact and the type of factors related to functional recoveries of patients with BAD may be different from other types of stroke. The present study suggested that clinical category of stroke should be taken into consideration in prediction of outcomes and planning of rehabilitation management.

Functional recovery of patients with intracerebral haemorrhage and cerebral infarction after rehabilitation.

To investigate potential differences in functional recovery after rehabilitation between intracerebral haemorrhage and cerebral infarction, we retrospectively compared the outcomes of patients with intracerebral haemorrhage (N = 208) and cerebral infarction (N = 480) who were consecutively discharged from our convalescent rehabilitation hospital between January 2013 and December 2018. Functional improvement was estimated by functional independence effectiveness measurements (proportion of potential for improvement achieved) upon discharge. Univariate analysis showed no significant differences in functional improvement between the two groups possibly because of the demographic variations upon admission. Multiple regression analysis demonstrated that the impact and type of factors related to functional improvement (functional independence measure upon admission, age, length of hospital stay, and time to admission after onset) were similar in both groups. Nevertheless, stratified analysis revealed, compared with patients with cerebral infarction, better improvement in patients with intracerebral haemorrhage that were admitted early after onset (<20 days), which exhibited high or moderate severity upon admission (functional independence measure: 36-89), or had a long hospital stay (>129 days). The present study showed differences as well as similarities in functional recovery between two stroke subtypes and suggests that better functional improvement might be expected in patients with intracerebral haemorrhage compared with those with cerebral infarction through an earlier start of intensive rehabilitation or longer rehabilitation in the hospital even if they exhibited relatively severe impairment upon admission. The type of stroke should be taken into consideration when predicting functional recovery and planning rehabilitation management in stroke patients.

New mutation of the Na channel in the severe form of potassium-aggravated myotonia.

Myotonia manifests in several hereditary diseases, including hyperkalemic periodic paralysis (HyperPP), paramyotonia congenita (PMC), and potassium-aggravated myotonia (PAM). These are allelic disorders originating from missense mutations in the gene that codes the skeletal muscle sodium channel, Nav1.4. Moreover, a severe form of PAM has been designated as myotonia permanens. A new mutation of Nav1.4, Q1633E, was identified in a Japanese family presenting with the PAM phenotype. The proband suffered from cyanotic attacks during infancy. The mutated amino acid residue is located on the EF-hand calcium-binding motif in the intracellular C-terminus. A functional analysis of the mutant channel using the voltage-clamp method revealed disruption of fast inactivation, a slower rate of current decay, and a depolarized shift in the voltage dependence of availability. This study has identified a new mutation of PAM with a severe phenotype and emphasizes the importance of the C-terminus for fast inactivation of the sodium channel. Muscle Nerve 39: 666-673, 2009.

Class Ic antiarrhythmics block human skeletal muscle Na channel during myotonia-like stimulation.

Flecainide, a class Ic antiarrhythmic drug, has been anecdotally reported to improve myotonia, but little is known about its kinetics on human skeletal muscle sodium channels applicable in vivo. Here we explored the anti-myotonic action of flecainide for human skeletal muscle sodium channels heterologously expressed in cultured cells. Flecainide blocked sodium channels in a highly state-dependent manner with 20-fold difference in IC(50) between use-dependent and tonic blocks. When pulses of brief depolarization simulating myotonia were applied from a holding potential of -90 mV, flecainide at therapeutic concentrations significantly blocked sodium currents. Flecainide slowed the time course of recovery but most channels recovered from block within 10-20 s. In contrast to mexiletine, flecainide did not markedly block sodium current during prolonged depolarization, suggesting an open-channel blocking action. Considering the slow recovery from block and the specific action against repetitive depolarization, flecainide may represent a potent therapeutic agent for myotonia.

Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a debilitating multisystemic disorder caused by a CTG repeat expansion in the DMPK gene. Aberrant splicing of several genes has been reported to contribute to some symptoms of DM1, but the cause of muscle weakness in DM1 and elevated Ca2+ concentrations in cultured DM muscle cells is unknown. Here, we investigated the alternative splicing of mRNAs of two major proteins of the sarcoplasmic reticulum, the ryanodine receptor 1 (RyR1) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) 1 or 2. The fetal variants, ASI(-) of RyR1 which lacks residue 3481-3485, and SERCA1b which differs at the C-terminal were significantly increased in skeletal muscles from DM1 patients and the transgenic mouse model of DM1 (HSA(LR)). In addition, a novel variant of SERCA2 was significantly decreased in DM1 patients. The total amount of mRNA for RyR1, SERCA1 and SERCA2 in DM1 and the expression levels of their proteins in HSA(LR) mice were not significantly different. However, heterologous expression of ASI(-) in cultured cells showed decreased affinity for [3H]ryanodine but similar Ca2+ dependency, and decreased channel activity in single-channel recording when compared with wild-type (WT) RyR1. In support of this, RyR1-knockout myotubes expressing ASI(-) exhibited a decreased incidence of Ca2+ oscillations during caffeine exposure compared with that observed for myotubes expressing WT-RyR1. We suggest that aberrant splicing of RyR1 and SERCA1 mRNAs might contribute to impaired Ca2+ homeostasis in DM1 muscle.