Kenneth Silver

Repetitive Bilateral Arm Training With Rhythmic Auditory Cueing Improves Motor Function in Chronic Hemiparetic Stroke

Background and Purpose Chronic upper extremity hemiparesis is a leading cause of functional disability after stroke. We investigated the hypothesis that bilateral arm training with rhythmic auditory cueing (BATRAC) will improve motor function in the hemiparetic arm of stroke patients. Methods In this single group pilot study we determined the effects of 6 weeks of BATRAC on 14 patients with chronic hemiparetic stroke (median time after stroke, 30 months) immediately after training and at 2 months after training. Four 5-minute periods per session (3 times per week) of BATRAC were performed with the use of a custom-designed arm training machine. Results The patients showed significant and potentially durable increases in the following: Fugl-Meyer Upper Extremity Motor Performance Test of impairment (P <0.0004), Wolf Motor Function Test (performance time measure, P <0.02), and University of Maryland Arm Questionnaire for Stroke measuring daily use of the hemiparetic arm (P <0.002). Isometric strength improved in elbow flexion (P <0.05) and wrist flexion (P <0.02) for the paretic arm and in elbow flexion (P <0.02) and wrist extension (P <0.02) for the nonparetic arm. Active range of motion improved for paretic-side shoulder extension (P <0.01), wrist flexion (P <0.004), and thumb opposition (P <0.002), and passive range of motion improved for paretic wrist flexion (P <0.03). Conclusions Six weeks of BATRAC improves functional motor performance of the paretic upper extremity as well as a few changes in isometric strength and range of motion. These benefits are largely sustained at 8 weeks after training cessation.

Treadmill Exercise Rehabilitation Improves Ambulatory Function and Cardiovascular Fitness in Patients With Chronic Stroke A Randomized, Controlled Trial

Background and Purpose— Physical inactivity propagates disability after stroke through physical deconditioning and learned nonuse. We investigated whether treadmill aerobic training (T-AEX) is more effective than conventional rehabilitation to improve ambulatory function and cardiovascular fitness in patients with chronic stroke. Methods— Sixty-one adults with chronic hemiparetic gait after ischemic stroke (>6 months) were randomized to 6 months (3×/week) progressive T-AEX or a reference rehabilitation program of stretching plus low-intensity walking (R-CONTROL). Peak exercise capacity (Vo2 peak), o2 consumption during submaximal effort walking (economy of gait), timed walks, Walking Impairment Questionnaire (WIQ), and Rivermead Mobility Index (RMI) were measured before and after 3 and 6 months of training. Results— Twenty-five patients completed T-AEX and 20 completed R-CONTROL. Only T-AEX increased cardiovascular fitness (17% versus 3%, &dgr;% T-AEX versus R-CONTROL, P<0.005). Group-by-time analyses revealed T-AEX improved ambulatory performance on 6-minute walks (30% versus 11%, P<0.02) and mobility function indexed by WIQ distance scores (56% versus 12%, P<0.05). In the T-AEX group, increasing training velocity predicted improved Vo2 peak (r=0.43, P<0.05), but not walking function. In contrast, increasing training session duration predicted improved 6-minute walk (r=0.41, P<0.05), but not fitness gains. Conclusions— T-AEX improves both functional mobility and cardiovascular fitness in patients with chronic stroke and is more effective than reference rehabilitation common to conventional care. Specific characteristics of training may determine the nature of exercise-mediated adaptations.

Treadmill Aerobic Exercise Training Reduces the Energy Expenditure and Cardiovascular Demands of Hemiparetic Gait in Chronic Stroke Patients A Preliminary Report

BACKGROUND AND PURPOSE Elevated energy costs of hemiparetic gait contribute to functional disability after stroke, particularly in physically deconditioned older patients. We investigated the effects of 6 months of treadmill aerobic exercise training on the energy expenditure and cardiovascular demands of submaximal effort ambulation in stroke patients with chronic hemiparetic gait. METHODS Nine older stroke patients with chronic hemiparetic gait were enrolled in a 6-month program of low-intensity aerobic exercise using a graded treadmill. Repeated measures of energy expenditure based on steady state oxygen consumption during a standardized 1-mph submaximal effort treadmill walking task were performed before and after training. RESULTS Six months of exercise training produced significant reductions in energy expenditure (n = 9; 3.40 +/- 0.27 versus 2.72 +/- 0.25 kcal/min [mean +/- SEM]; P < .005) during a given submaximal effort treadmill walking task. Repeated measures analysis in the subset of patients (n = 8) tested at baseline and after 3 and 6 months revealed that reductions in energy expenditure were progressive (F = 11.1; P < .02) and that exercise-mediated declines in both oxygen consumption (F = 9.7; P < .02) and respiratory exchange ratio (F = 13.4; P < .01) occurred in a strong linear pattern. These stroke patients could perform the same standardized submaximal exercise task at progressively lower heart rates after 3 months (96 +/- 4 versus 87 +/- 4 beats per minute) and 6 months of training (82 +/- 4 beats per minute; F = 35.4; P < .002). CONCLUSIONS Six months of low-intensity treadmill endurance training produces substantial and progressive reductions in the energy expenditure and cardiovascular demands of walking in older patients with chronic hemiparetic stroke. This suggests that task-oriented aerobic exercise may improve functional mobility and the cardiovascular fitness profile in this population.

De novo mutations in ATP1A3 cause alternating hemiplegia of childhood

Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurological manifestations. AHC is usually a sporadic disorder and has unknown etiology. We used exome sequencing of seven patients with AHC and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation in a case of familial AHC. Notably, most AHC cases are caused by one of seven recurrent ATP1A3 mutations, one of which was observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset dystonia-parkinsonism, AHC-causing mutations in this gene caused consistent reductions in ATPase activity without affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3.

Medical treatment of Rasmussen's syndrome (chronic encephalitis and epilepsy): Effect of high‐dose steroids or immunoglobulins in 19 patients

We treated 19 patients with Rasmussens syndrome (chronic encephalitis and epilepsy)–a rare progressive disorder of unknown etiology causing focal epilepsy, hemiparesis, and intellectual deterioration–with intravenous immunoglobulins, high-dose steroids, or both, to control seizures and improve the end point of the disease. Ten of 17 patients receiving steroids, and eight of nine patients receiving immunoglobulins, had some reduction of seizure frequency in the short term. Improvement in hemiparesis was slight. The effect of these drugs in ameliorating the end point of the disease in the long term remains unknown, and further multicenter studies with standardized protocols are warranted.

Microprocessor-based ambulatory activity monitoring in stroke patients

PURPOSE Recovery of ambulatory function after stroke is routinely assessed using standardized subject- or observer-rated instruments that do not directly measure ambulatory activities in the home-community setting. Accuracy of conventional pedometers in stroke patients is not established, limiting their application in mobility outcomes monitoring. This study investigates the accuracy and reliability of a mechanical pedometer versus microprocessor-based step activity monitoring (SAM) in gait-impaired hemiparetic stroke patients. METHODS Accuracy and test-retest reliability of ankle-worn SAM and belt-worn pedometer were tested directly against hand tallied stride counts and cadence during a battery of timed walks in 16 chronic hemiparetic stroke patients. Patients performed replicate 1-min floor walks at self-selected and fastest comfortable paces, and two 6-min walks on separate days. RESULTS SAM cadence and total stride counts are more accurate than pedometers during 1-min walks at self-selected (99 +/- 1 vs 87 +/- 11.3%, mean +/- SD, P < 0.01); fast pace (98 +/- 2.3% vs 85 +/- 15%, P < 0.01); and repeated 6-min walks performed on separate days (99 +/- 1% vs 89 +/- 12%, P < 0.01). Although SAM is highly reliable (r = 0.97, P < 0.0001) and accurate in all patients under every walking condition tested, the mechanical pedometer demonstrates this high level of accuracy in only half of stroke patients and has poor test-retest reliability (r = 0.64, P < 0.05). CONCLUSION SAM, but not the conventional pedometer, provides accurate and reliable measures of cadence and total stride counts in hemiparetic stroke patients. Portable microprocessor-based gait monitoring offers potential to quantitatively measure home-community-based ambulatory activity levels in this population.

Familial perisylvian polymicrogyria: a new familial syndrome of cortical maldevelopment

Two familial X‐linked dominant syndromes of cortical maldevelopment have recently been described: double cortex/lissencephaly syndrome and bilateral periventricular nodular heterotopia. We report on 12 kindreds with familial perisylvian polymicrogyria (FPP) presenting at 10 centers, examine the clinical presentation in these familial cases, and propose a possible mode of inheritance. The clinical and radiological pattern was variable among the 42 patients, with clinical differences among the families and even within members of the same family. Pseudobulbar signs, cognitive deficits, epilepsy, and perisylvian abnormalities on imaging studies were not found in all patients. When present, they displayed a spectrum of severity. The only clear correlation in this study was between bilateral imaging findings and abnormal tongue movements and/or pronounced dysarthria. Most of the families provided evidence suggestive of, or compatible with, X‐linked transmission. On the other hand, the pedigrees of 2 families ruled out X‐linked inheritance. The most likely mode of inheritance for these 2 families was autosomal dominant with decreased penetrance; however, autosomal recessive inheritance with pseudodominance could not be ruled out in 1 family. We conclude that FPP appears to be genetically heterogeneous. However, most of the families probably represent a third previously undescribed X‐linked syndrome of cortical maldevelopment. Ann Neurol 2000;48:39–48

Split-Belt Treadmill Adaptation Transfers to Overground Walking in Persons Poststroke

Background and Objective. Following stroke, subjects retain the ability to adapt interlimb symmetry on the split-belt treadmill. Critical to advancing our understanding of locomotor adaptation and its usefulness in rehabilitation is discerning whether adaptive effects observed on a treadmill transfer to walking over ground. We examined whether aftereffects following split-belt treadmill adaptation transfer to overground walking in healthy persons and those poststroke. Methods. Eleven poststroke and 11 age-matched and gender-matched healthy subjects walked over ground before and after walking on a split-belt treadmill. Adaptation and aftereffects in step length and double support time were calculated. Results. Both groups demonstrated partial transfer of the aftereffects observed on the treadmill (P < .001) to overground walking ( P < .05), but the transfer was more robust in the subjects poststroke (P < .05). The subjects with baseline asymmetry after stroke improved in asymmetry of step length and double limb support (P = .06). Conclusions. The partial transfer of aftereffects to overground walking suggests that some shared neural circuits that control locomotion for different environmental contexts are adapted during split-belt treadmill walking. The larger adaptation transfer from the treadmill to overground walking in the stroke survivors may be due to difficulty adjusting their walking pattern to changing environmental demands. Such difficulties with context switching have been considered detrimental to function poststroke. However, we propose that the persistence of improved symmetry when changing context to overground walking could be used to advantage in poststroke rehabilitation.

Proton MR spectroscopic characterization of differences in regional brain metabolic abnormalities in mitochondrial encephalomyopathies

Localized brain proton MR spectra were acquired from patients with different mitochondrial encephalomyopathies (myoclonus epilepsy with ragged-red fibers [MERRF], Kearns-Sayre syndrome [KSS], and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes [MELAS]). The regional brain metabolic abnormalities in patients with these syndromes showed different features consistent with the distinct phenotypes. In MERRF, only one of four patients showed an increase in the lactate/creatine resonance intensity ratio (an index of impairment of oxidative metabolism) in spectra from central (supraventricular) or occipital brain volumes, and this was small. There were significant decreases in N-acetylaspartate/creatine (a measure of neuronal loss or dysfunction) in central cerebral volumes of demented patients and, more prominently, in occipital volumes. In the one patient in whom it was studied, the cerebellum also showed a decreased N-acetylaspartate/creatine. Spectra from two patients with KSS both showed large (four- to sevenfold) increases in lactate/creatine and large decreases in N-acetylaspartate/creatine in central brain volumes. Yet another pattern of regional metabolic abnormality was present in the MELAS syndrome, where proton spectroscopic imaging demonstrated focal localization of abnormally increased lactate/creatine and decreased N-acetylaspartate/creatine to the regions of the stroke-like lesions on conventional MR images. Serial studies emphasized that the regional metabolic abnormalities in MELAS are highly variable as the stroke-like lesions appear and evolve.

Alternating hemiplegia of childhood or familial hemiplegic migraine?: A novel ATP1A2 mutation

Alternating hemiplegia of childhood (AHC) is typically distinguished from familial hemiplegic migraine (FHM) by infantile onset of the characteristic symptoms and high prevalence of associated neurological deficits that become increasingly obvious with age. Expansion of the clinical spectrum in FHM recently has begun to blur the distinction between these disorders. We report a novel ATP1A2 mutation in a kindred with features that bridge the phenotypic spectrum between AHC and FHM syndromes, supporting a possible common pathogenesis in a subset of such cases. Mutation analysis in classic sporadic AHC patients and in an additional five kindreds in which linkage to the ATP1A2 locus could not be excluded failed to identify additional mutations. Ann Neurol 2004;55:884–887