Clinically important effect sizes for clinical trials using infarct growth reduction as the primary outcome: a systematic review.

Background: Infarct growth on multimodal imaging is a common lead outcome in phase 2 proof-of-concept and dose-optimization neuroprotective agent stroke trials. However, the effect size in infarct growth reduction that correlates with clinically meaningful differences in clinical global disability outcomes has not been well delineated.

Methods: A systematic literature search identified all endovascular thrombectomy randomized trials reporting magnitude of treatment effect on both infarct growth reduction and increase in functional independence (modified Rankin Scale (mRS) 0-2).

The insidious impact of under-diagnosed proximal weakness induced by statins.

: This Perspective reassesses the consensus opinion that statin-associated muscle symptoms (SAMS) occur in <1% of users and associated myopathic proximal muscle weakness is even more rare.: Of the over 180,000 participants in clinical trials and large registries of statin users, only a few studies have included a standard manual muscle test (MMT), dynamometry or a focused questionnaire to assess for proximal weakness and related disability in daily and recreational activities. Formal strength testing suggests, however, that weakness can be demonstrated in at least 10% of users.

Paired Associative Stimulation as a Tool to Assess Plasticity Enhancers in Chronic Stroke.

Background And Purpose: The potential for adaptive plasticity in the post-stroke brain is difficult to estimate, as is the demonstration of central nervous system (CNS) target engagement of drugs that show promise in facilitating stroke recovery. We set out to determine if paired associative stimulation (PAS) can be used (a) as an assay of CNS plasticity in patients with chronic stroke, and (b) to demonstrate CNS engagement by memantine, a drug which has potential plasticity-modulating effects for use in motor recovery following stroke.

Methods: We examined the effect of PAS in fourteen participants with chronic hemiparetic stroke at five time-points in a within-subjects repeated measures design study: baseline off-drug, and following a week of orally administered memantine at doses of 5, 10, 15, and 20 mg, comprising a total of seventy sessions.

Wearable Sensors to Monitor, Enable Feedback, and Measure Outcomes of Activity and Practice.

Purpose Of Review: Measurements obtained during real-world activity by wearable motion sensors may contribute more naturalistic accounts of clinically meaningful changes in impairment, activity, and participation during neurologic rehabilitation, but obstacles persist. Here we review the basics of wearable sensors, the use of existing systems for neurological and rehabilitation applications and their limitations, and strategies for future use.

Recent Findings: Commercial activity-recognition software and wearable motion sensors for community monitoring primarily calculate steps and sedentary time.

Cost-effectiveness of percutaneous patent foramen ovale closure as secondary stroke prevention.

Objective: Compared to medical therapy alone, percutaneous closure of patent foramen ovale (PFO) further reduces risk of recurrent ischemic strokes in carefully selected young to middle-aged patients with a recent cryptogenic ischemic stroke. The objective of this study was to evaluate the cost-effectiveness of this therapy in the context of the United Kingdom (UK) healthcare system.

Methods: A Markov cohort model consisting of four health states (Stable after index stroke, Post-Minor Recurrent Stroke, Post-Moderate Recurrent Stroke, and Death) was developed to simulate the economic outcomes of device-based PFO closure compared to medical therapy.

Behavioral self-management strategies for practice and exercise should be included in neurologic rehabilitation trials and care.

Purpose Of Review: Rehabilitation trials and postacute care to lessen impairments and disability after stroke, spinal cord injury, and traumatic brain injury almost never include training to promote long-term self-management of skills practice, strengthening and fitness. Without behavioral training to develop self-efficacy, clinical trials, and home-based therapy may fail to show robust results.

Recent Findings: Behavioral theories about self-management and self-efficacy for physical activity have been successfully incorporated into interventions for chronic diseases, but rarely for neurologic rehabilitation.

Curiosity and cure: translational research strategies for neural repair-mediated rehabilitation.

Clinicians who seek interventions for neural repair in patients with paralysis and other impairments may extrapolate the results of cell culture and rodent experiments into the framework of a preclinical study. These experiments, however, must be interpreted within the context of the model and the highly constrained hypothesis and manipulation being tested. Rodent models of repair for stroke and spinal cord injury offer examples of potential pitfalls in the interpretation of results from developmental gene activation, transgenic mice, endogeneous neurogenesis, cellular transplantation, axon regeneration and remyelination, dendritic proliferation, activity-dependent adaptations, skills learning, and behavioral testing.

Behavioral, temporal, and spatial targets for cellular transplants as adjuncts to rehabilitation for stroke.

Stem cell and more differentiated neural cell transplantation strategies are an intriguing approach for neural repair to augment rehabilitation interventions after stroke. In the cortex, exogenous cells could create, augment, or extend in time endogenous peri-infarct and remote molecular signals, such as those for neurogenesis, cell differentiation, axonal and dendritic sprouting, network connectivity, and long-term potentiation, as well as deliver engineered genes and provide replacement cells in a network. If demyelinated axons exist in the periphery of an infarct, they could be targets for remyelination to reestablish conductivity.

Weight-supported treadmill vs over-ground training for walking after acute incomplete SCI.

Objective: To compare the efficacy of step training with body weight support on a treadmill (BWSTT) with over-ground practice to the efficacy of a defined over-ground mobility therapy (CONT) in patients with incomplete spinal cord injury (SCI) admitted for inpatient rehabilitation.

Methods: A total of 146 subjects from six regional centers within 8 weeks of SCI were entered in a single-blinded, multicenter, randomized clinical trial (MRCT). Subjects were graded on the American Spinal Injury Association Impairment Scale (ASIA) as B, C, or D with levels from C5 to L3 and had a Functional Independence Measure for locomotion (FIM-L) score < 4.

Underappreciated statin-induced myopathic weakness causes disability.

Introduction: Myopathic syndromes induced by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) include muscle complaints, myalgia, myositis, and rhabdomyolysis. No prospective study of statins, however, included tests of strength, so the incidence of weakness, with or without muscle symptoms and elevated enzymes, is unknown, and perhaps overlooked.

Methods: From a convenience sample of patients referred to an outpatient neurorehabilitation clinic over the course of 1 year, 8 patients with hemiparetic stroke and 10 patients with other presumed neurologic diseases presented with new difficulty walking by 3 to 12 months after starting one of 3 statins.

Neurobiology of rehabilitation.

Rehabilitation aims to lessen the physical and cognitive impairments and disabilities of patients with stroke, multiple sclerosis, spinal cord or brain injury, and other neurologic diseases. Conventional approaches beyond compensatory adjustments to disability may be augmented by applying some of the myriad experimental results about mechanisms of intrinsic biological changes after injury and the effects of extrinsic manipulations on spared neuronal assemblies. The organization and inherent adaptability of the anatomical nodes within distributed pathways of the central nervous system offer a flexible substrate for treatment strategies that drive activity-dependent plasticity.

Residual motor control and cortical representations of function following hemispherectomy: effects of etiology.

Fifteen posthemispherectomy children were examined to assess residual motor function of the paretic side using the 74-point Fugl-Meyer Assessment of Motor Recovery scale. The degree of residual motor control differed for upper and lower extremities, with hand function being most severely impaired. Posthemispherectomy motor outcomes also differed as a function of etiology: cortical dysplasia, perinatal infarct, and Rasmussen's encephalitis.

Ankle dorsiflexion as an fMRI paradigm to assay motor control for walking during rehabilitation.

The ability to walk independently with the velocity and endurance that permit home and community activities is a highly regarded goal for neurological rehabilitation after stroke. This pilot study explored a functional magnetic resonance imaging (fMRI) activation paradigm for its ability to reflect phases of motor learning over the course of locomotor rehabilitation-mediated functional gains. Ankle dorsiflexion is an important kinematic aspect of the swing and initial stance phase of the gait cycle.

The neural substrates of religious experience.

Religious experience is brain-based, like all human experience. Clues to the neural substrates of religious-numinous experience may be gleaned from temporolimbic epilepsy, near-death experiences, and hallucinogen ingestion. These brain disorders and conditions may produce depersonalization, derealization, ecstasy, a sense of timelessness and spacelessness, and other experiences that foster religious-numinous interpretation.

Localization of partial epilepsy using magnetic and electric measurements.

Dipole methods applied to brain electric and magnetic fields have made several significant advances in investigation of epilepsy and sensorimotor cortex. The magnetoencephalogram (MEG) and the MEG-electroencephalogram (EEG) combination have contributed substantially. The MEG-EEG combination has shown a mean accuracy of somatosensory evoked response (SER) localization of the central fissure similar to electrocorticography (ECoG), resolution of ambiguity in ECoG of alternative configurations of hand sensorimotor cortex, and resolution of ambiguity of the causes of the difference between EEG and ECoG map patterns.

Huntington disease: finding the gene and after.

Huntington disease is an autosomal dominant disorder that usually begins in mid-life and is characterized by progressive choreiform movements and dementia. Approximately 5% of patients develop symptoms prior to 14 years of age. In most juvenile cases, the gene is transmitted from the father.