A Home-Based Telerehabilitation Program for Patients With Stroke.

BACKGROUND: Although rehabilitation therapy is commonly provided after stroke, many patients do not derive maximal benefit because of access, cost, and compliance. A telerehabilitation-based program may overcome these barriers. We designed, then evaluated a home-based telerehabilitation system in patients with chronic hemiparetic stroke. METHODS: Patients were 3 to 24 months poststroke with stable arm motor deficits. Each received 28 days of telerehabilitation using a system delivered to their home. Each day consisted of 1 structured hour focused on individualized exercises and games, stroke education, and an hour of free play. RESULTS: Enrollees (n = 12) had baseline Fugl-Meyer (FM) scores of 39 ± 12 (mean ± SD). Compliance was excellent: participants engaged in therapy on 329/336 (97.9%) assigned days. Arm repetitions across the 28 days averaged 24,607 ± 9934 per participant. Arm motor status showed significant gains (FM change 4.8 ± 3.8 points, P = .0015), with half of the participants exceeding the minimal clinically important difference. Although scores on tests of computer literacy declined with age ( r = -0.92; P < .0001), neither the motor gains nor the amount of system use varied with computer literacy. Daily stroke education via the telerehabilitation system was associated with a 39% increase in stroke prevention knowledge ( P = .0007). Depression scores obtained in person correlated with scores obtained via the telerehabilitation system 16 days later ( r = 0.88; P = .0001). In-person blood pressure values closely matched those obtained via this system ( r = 0.99; P < .0001). CONCLUSIONS: This home-based system was effective in providing telerehabilitation, education, and secondary stroke prevention to participants. Use of a computer-based interface offers many opportunities to monitor and improve the health of patients after stroke.

Dopamine genetic risk score predicts depressive symptoms in healthy adults and adults with depression.

BACKGROUND: Depression is a common source of human disability for which etiologic insights remain limited. Although abnormalities of monoamine neurotransmission, including dopamine, are theorized to contribute to the pathophysiology of depression, evidence linking dopamine-related genes to depression has been mixed. The current study sought to address this knowledge-gap by examining whether the combined effect of dopamine polymorphisms was associated with depressive symptomatology in both healthy individuals and individuals with depression. METHODS: Data were drawn from three independent samples: (1) a discovery sample of healthy adult participants (n = 273); (2) a replication sample of adults with depression (n = 1,267); and (3) a replication sample of healthy adult participants (n = 382). A genetic risk score was created by combining functional polymorphisms from five genes involved in synaptic dopamine availability (COMT and DAT) and dopamine receptor binding (DRD1, DRD2, DRD3). RESULTS: In the discovery sample, the genetic risk score was associated with depressive symptomatology (ß = -0.80, p = 0.003), with lower dopamine genetic risk scores (indicating lower dopaminergic neurotransmission) predicting higher levels of depression. This result was replicated with a similar genetic risk score based on imputed genetic data from adults with depression (ß = -0.51, p = 0.04). Results were of similar magnitude and in the expected direction in a cohort of healthy adult participants (ß = -0.86, p = 0.15). CONCLUSIONS: Sequence variation in multiple genes regulating dopamine neurotransmission may influence depressive symptoms, in a manner that appears to be additive. Further studies are required to confirm the role of genetic variation in dopamine metabolism and depression.

Corticospinal excitability as a predictor of functional gains at the affected upper limb following robotic training in chronic stroke survivors.

BACKGROUND: Robotic training can help improve function of a paretic limb following a stroke, but individuals respond differently to the training. A predictor of functional gains might improve the ability to select those individuals more likely to benefit from robot-based therapy. Studies evaluating predictors of functional improvement after a robotic training are scarce. One study has found that white matter tract integrity predicts functional gains following a robotic training of the hand and wrist. Objective. To determine the predictive ability of behavioral and brain measures in order to improve selection of individuals for robotic training. METHODS: Twenty subjects with chronic stroke participated in an 8-week course of robotic exoskeletal training for the arm. Before training, a clinical evaluation, functional magnetic resonance imaging (fMRI), diffusion tensor imaging, and transcranial magnetic stimulation (TMS) were each measured as predictors. Final functional gain was defined as change in the Box and Block Test (BBT). Measures significant in bivariate analysis were fed into a multivariate linear regression model. RESULTS: Training was associated with an average gain of 6 ± 5 blocks on the BBT (P < .0001). Bivariate analysis revealed that lower baseline motor-evoked potential (MEP) amplitude on TMS, and lower laterality M1 index on fMRI each significantly correlated with greater BBT change. In the multivariate linear regression analysis, baseline MEP magnitude was the only measure that remained significant. CONCLUSION: Subjects with lower baseline MEP magnitude benefited the most from robotic training of the affected arm. These subjects might have reserve remaining for the training to boost corticospinal excitability, translating into functional gains.

Pharmacogenetics of neural injury recovery.

Relatively few pharmacological agents are part of routine care for neural injury, although several are used or under consideration in acute stroke, chronic stroke, traumatic brain injury and secondary stroke prevention. Tissue plasminogen activator is approved for the treatment of acute ischemic stroke, and genetic variants may impact the efficacy and safety of this drug. In the chronic phase of stroke, several drugs such as L-dopa, fluoxetine and donepezil are under investigation for enhancing rehabilitation therapy, with varying levels of evidence. One potential reason for the mixed efficacy displayed by these drugs may be the influence of genetic factors that were not considered in prior studies. An understanding of the genetics impacting the efficacy of dopaminergic, serotonergic and cholinergic drugs may allow clinicians to target these potential therapies to those patients most likely to benefit. In the setting of stroke prevention, which is directly linked to neural injury recovery, the most highly studied pharmacogenomic interactions pertain to clopidogrel and warfarin. Incorporating pharmacogenomics into neural injury recovery has the potential to maximize the benefit of several current and potential pharmacological therapies and to refine the choice of pharmacological agent that may be used to enhance benefits from rehabilitation therapy.

Genetic variation in the human brain dopamine system influences motor learning and its modulation by L-Dopa.

Dopamine is important to learning and plasticity. Dopaminergic drugs are the focus of many therapies targeting the motor system, where high inter-individual differences in response are common. The current study examined the hypothesis that genetic variation in the dopamine system is associated with significant differences in motor learning, brain plasticity, and the effects of the dopamine precursor L-Dopa. Skilled motor learning and motor cortex plasticity were assessed using a randomized, double-blind, placebo-controlled, crossover design in 50 healthy adults during two study weeks, one with placebo and one with L-Dopa. The influence of five polymorphisms with established effects on dopamine neurotransmission was summed using a gene score, with higher scores corresponding to higher dopaminergic neurotransmission. Secondary hypotheses examined each polymorphism individually. While training on placebo, higher gene scores were associated with greater motor learning (p = .03). The effect of L-Dopa on learning varied with the gene score (gene score*drug interaction, p = .008): participants with lower gene scores, and thus lower endogenous dopaminergic neurotransmission, showed the largest learning improvement with L-Dopa relative to placebo (p<.0001), while L-Dopa had a detrimental effect in participants with higher gene scores (p = .01). Motor cortex plasticity, assessed via transcranial magnetic stimulation (TMS), also showed a gene score*drug interaction (p = .02). Individually, DRD2/ANKK1 genotype was significantly associated with motor learning (p = .02) and its modulation by L-Dopa (p<.0001), but not with any TMS measures. However, none of the individual polymorphisms explained the full constellation of findings associated with the gene score. These results suggest that genetic variation in the dopamine system influences learning and its modulation by L-Dopa. A polygene score explains differences in L-Dopa effects on learning and plasticity most robustly, thus identifying distinct biological phenotypes with respect to L-Dopa effects on learning and plasticity. These findings may have clinical applications in post-stroke rehabilitation or the treatment of Parkinson's disease.

The influence of genetic factors on brain plasticity and recovery after neural injury.

PURPOSE OF REVIEW: The fields of clinical genetics and pharmacogenetics are rapidly expanding. Genetic factors have numerous associations with injury and with treatment effects in the setting of neural plasticity and recovery. RECENT FINDINGS: Evidence is reviewed that established genetic variants, as well as some more recently described variants, are related to outcome after neural injury and in some cases are useful for predicting clinical course. In many cases, the interaction of genetics with clinical factors such as experience and therapy may be important. As an extension of this, genetic factors have been associated with differential response to a number of forms of therapy, including pharmacological, brain stimulation, psychotherapy, and meditation. Genetic variation might also have a significant effect on plasticity and recovery through key covariates such as depression or stress. A key point is that genetic associations might be most accurately identified when studied in relation to distinct forms of a disorder rather than in relation to broad clinical syndromes. SUMMARY: Understanding genetic variation gives clinicians a biological signal that could be used to predict who is most likely to recover from neural injury, to choose the optimal treatment for a patient, or to supplement rehabilitation therapy.

Intense training overcomes effects of the Val66Met BDNF polymorphism on short-term plasticity.

The val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene impacts activity-dependent secretion of BDNF and modifies short-term cortical plasticity. The current study examined whether sustained training overcomes polymorphism effects on short-term plasticity and also examined polymorphism effects on long-term plasticity. Twenty-four subjects completed a 12-day protocol of daily training on a marble navigation task that required intense use of the first dorsal interosseus (FDI) muscle. In parallel, transcranial magnetic stimulation (TMS) mapping was used to assess serial measures of short-term cortical motor map plasticity, plus long-term cortical motor map plasticity, of the cortical FDI map. On Day 1, subjects with the polymorphism did not show significant short-term cortical motor map plasticity over 30 min of FDI activity, but subjects without the polymorphism did. After 5 days of intense training, a genotype-based difference in short-term cortical motor map plasticity was no longer found, as both groups showed short-term plasticity across the 30 min of FDI activity. Also, across 12 days of training, map area decreased significantly, in a manner that did not vary in relation to genotype. Training of sufficient intensity and duration overcomes effects that the val(66)met polymorphism has on short-term cortical motor map plasticity. The polymorphism-related differences seen with short-term plasticity are not found with long-term cortical motor map plasticity.

Genetic influences on neural plasticity.

Neural plasticity refers to the capability of the brain to alter function or structure in response to a range of events and is a crucial component of both functional recovery after injury and skill learning in healthy individuals. A number of factors influence neural plasticity and recovery of function after brain injury. The current review considers the impact of genetic factors. Polymorphisms in the human genes coding for brain-derived neurotrophic factor and apolipoprotein E have been studied in the context of plasticity and stroke recovery and are discussed here in detail. Several processes involved in plasticity and stroke recovery, such as depression or pharmacotherapy effects, are modulated by other genetic polymorphisms and are also discussed. Finally, new genetic polymorphisms that have not been studied in the context of stroke are proposed as new directions for study. A better understanding of genetic influences on recovery and response to therapy might allow improved treatment after a number of forms of central nervous system injury.

Brain plasticity and genetic factors.

Brain plasticity refers to changes in brain function and structure that arise in a number of contexts. One area in which brain plasticity is of considerable interest is recovery from stroke, both spontaneous and treatment-induced. A number of factors influence these poststroke brain events. The current review considers the impact of genetic factors. Polymorphisms in the human genes coding for brain-derived neurotrophic factor (BDNF) and apolipoprotein E (ApoE) have been studied in the context of plasticity and/or stroke recovery and are discussed here in detail. Several other genetic polymorphisms are indirectly involved in stroke recovery through their modulating influences on processes such as depression and pharmacotherapy effects. Finally, new genetic polymorphisms that have not been studied in the context of stroke are proposed as new directions for study. A better understanding of genetic influences on recovery and response to therapy might allow improved treatment after stroke.