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Bihemispheric Brain Stimulation Plus Occupational/Physical Therapy Augments Motor Recovery in Chronic Stroke Patients



ARTICLE IN BRIEF

CONTRASTING POST-INTERVENTION VS. PREINTERVENTION

movements of the affected upper limb overlaid onto a standard anatomic template. Both wrist (blue) and elbow (red) movements yielded stronger activations of ipsilesional primary motor/premotor cortex after the five-day intervention. For the elbow movement task, the cluster was located in primary motor cortex. For the wrist movement task, one cluster was located at the border between primary motor and premotor cortex; an additional positive activation change was found in the contralesional inferior frontal gyrus.

The combination of bihemispheric transcranial direct current stimulation and peripheral sensorimotor activies improved motor functions in chronic stroke patients that outlasted the intervention period.

In a randomized, placebo-controlled trial, a combination of non-invasive, bihemispheric brain stimulation and simultaneous physical and occupational therapy (PT/OT) promoted greater motor recovery in chronic stroke patients than PT/OT alone, according to a study that appeared online Nov. 10 in Neurology.

The dual intervention also produced a significantly stronger activation of intact portions of the ipsilesional motor cortex, compared to patients who received sham stimulation. The study authors targeted ipsilesional motor regions because previous functional neuroimaging studies showed that reactivation of intact portions of the ipsilesional motor cortex was associated with better outcome after stroke.

The investigators used transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique that uses low amplitude direct currents applied via scalp electrodes to inject currents in the brain and thus modulate the level of excitability. Electrodes were placed on the arm/hand representation areas of both motor cortices, said senior study author Gottfried Schlaug, MD, PhD, associate professor of neurology at Harvard Medical School, in an e-mail to Neurology Today. Due to the size of the electrodes, adjacent primary and non-primary motor regions, as well as the sensory cortex, were also modulated.

DR. GOTTFRIED SCHLAUG

: “The rationale for applying bihemispheric tDCS and peripherial PT/OT [physical therapy/occupational therapy] was that dual hemispheric stimulation could affect both of these processes in the same sessions...Combining brain stimulation with PT/OT might enhance the therapeutic effects of each intervention by itself and potentiate neuroplastic effects.”

“The rationale for applying bihemispheric tDCS and peripherial PT/OT was that dual hemispheric stimulation could affect both of these processes in the same sessions,” said Dr. Schlaug. “Combining brain stimulation with PT/OT might enhance the therapeutic effects of each intervention by itself and potentiate neuroplastic effects.”

In an accompanying editorial in the same issue, Lalit Kalra, MD, PhD, professor of stroke medicine in the Departments of Diabetes, Endocrinology, and Internal Medicine at King's College in London, and Paolo M. Rossini, MD, PhD, professor of neurology at the University Campus Bio-Medico in Rome, Italy, wrote: “[This] is the first study to combine these [two] approaches in stroke patients undergoing physical rehabilitation. Hence, it illustrates how conceptual advances in the neuroscience of recovery can be translated into clinical practice and used in conjunction with established rehabilitation techniques.”

PROTOCOLS, RESULTS

Investigators randomly assigned 20 chronic stroke patients to receive five-consecutive sessions of either 30 minutes of tDCS or sham stimulation, while simultaneously receiving 60 minutes of PT/OT. Patients had an ischemic stroke at least five months before the study and no subsequent strokes. Subjects in both groups were also similar with regard to lesion size and location, ensuring that all patients had a similar impairment of their corticospinal motor system.

Prior to the study all patients completed two motor impairment assessments: the Upper Extremity Fugl-Meyer (UE-FM) — which assesses single- and multi-joint movements, such as the extension and flexion of the fingers or wrist — and the Wolf Motor Function Test (WMFT), which times proximal and distal movements, including reaching and grasping, and goal-directed movements, such as lifting a pencil, said Robert Lindenberg, MD, professor of neurology at the Beth Israel Deaconess Medical Center and one of the study authors, in an e-mail to Neurology Today.

Participants also underwent a functional MRI at baseline, while performing repetitive elbow and wrist extension and flexion exercises to measure activation of the intact ipsilesional motor regions.

In the dual treatment group, there was a 20 percent improvement in the overall function of the affected arms, and patients could complete tasks in substantially less time, said Dr. Schlaug, as evidenced by scores on the two tests. For example, there was a 20.7 percent increase in UE-FM scores, compared to 3.2 percent in the sham group; and a decrease of 19.1 percent in the WMFT in the experimental group versus 6.0 percent in the sham group. The effects of the stimulation persisted past the study duration by at least a week.

Investigators also observed on fMRI studies significantly greater activation of the ipsilesional motor cortex in the experimental group, while performing extension and flexion exercises. No significant changes were found in the sham cohort.

This suggests that a combined approach of non-invasive brain stimulation targeting both sides of the brain and peripheral sensorimotor stimulation leads to about a threefold higher benefit than sham stimulation with PT/OT. This increase in motor function was shown to be associated with a functional reorganization of the intact portions of the motor cortex on the lesional hemisphere, said Dr. Lindenberg.

BRAIN MODEL OF ALTERED INTERHEMISPHERIC INTERACTION IN PATIENTS WITH A UNIHEMISPHERIC STROKE

: The balance of interhemispheric inhibition becomes disrupted after a stroke (A). This leaves the healthy hemisphere in a position that it could exert too much of an unopposed influence onto the lesional hemisphere and possibly interfere in the recovery process. There are three possible ways to ameliorate this process: either the excitability in the affected (lesional) hemisphere (B) is upregulated, the excitability in the unaffected (normal) hemisphere (C) is downregulated or a combination of both approaches (D).

EXPERTS COMMENT

“Anything that produces this kind of improvement in such a short period of time with a safe, inexpensive treatment has a large clinical potential,” said George Wittenberg, MD, PhD, associate professor of neurology at the University of Maryland School of Medicine and VA Geriatric Research Education and Clinical Center staff physician, who wasn't involved with the study, in an interview with -Neurology Today. He was particularly surprised by the effect size of the UE-FM test since it was “a large and significant change for a relatively short course of therapy.”

Dr. Wittenberg said that a limitation of the study, however, was its small sample size, a view shared by the editorial authors.

“A single-center, small study in a highly selected group of subjects receiving standardized interventions in a homogenous environment and followed up for a relatively short period of time cannot be considered definitive or widely generalizable,” they wrote.

DR.GEORGE WITTENBERG

: “Anything that produces this kind of improvement in such a short period of time with a safe, inexpensive treatment has a large clinical potential.”

Dr. Schlaug acknowledged that longer follow-up studies are needed to determine whether the combination of tDCS with peripheral stimulation yields long-lasting effects. He noted that his group is already investigating other variations of the intervention such as the effects of number of sessions on treatment outcome. He also suggested “combining these studies with brain imaging to determine whether long-lasting effects are supported by functional and structural changes.”

The Neurology editorial authors also indicated that the clinical implications of the study's findings remains to be seen: “Bihemispheric tDCS resulted in significant arm function test scores, but whether these translate into increased independence in activities in daily life is not known. The sustainability of effect also remains unproven; rehabilitation studies require the benefits to be sustained for 12 weeks to one year.”

Dr. Wittenberg stated that since the study was performed on patients who had a stroke at least five months earlier, the results don't reveal possible effects that may have been realized if performed earlier. “They could potentially be greater and that would be very exciting,” he added.

TRANSCRANIAL MAGNETIC STIMULATION VERSUS TRANSCRANIAL DIRECT CURRENT STIMULATION

There are two methods available to stimulate the brain non-invasively: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), said Dr. Schlaug. Compared to TMS, tDCS does not directly lead to neuronal discharges, it only modulates the excitability level of brain tissue.

In tDCS large electrodes are typically used to influence a network of brain regions, which might be particularly useful in stroke recovery research since multiple brain regions have been shown to play a role in the recovery process, he said. tDCS has a sham mode and is portable, which helps to combine non-invasive brain stimulation in real-time with other activities/therapies such as physical/occupational therapy or speech therapy. In addition, tDCS can be used in a dual mode, increasing excitability on one hemisphere and decreasing excitability on the other hemisphere.

FOR MORE ABOUT MOTOR RECOVERY POST-STROKE

Want to hear more about on the effects of bihemispheric brain stimulation on motor recovery post-stroke? Tune in to the extended podcast interview on neurology.org on Dec. 14 when stroke expert Brett Kisella, MD, professor and vice chair of education and clinical services at the University of Cincinnati Neuroscience Institute in Ohio, interviews lead author Gottfried Schlaug, MD, PhD, and his coauthors about their work.

REFERENCES:


Lindenberg R, Renga V, Schlaug G, et al. Bihemispheric brain stimulation facilitates motor recovery in chronic stroke patients. Neurology 2010; E-pub 2010 Nov. 10.
    Kalra L, Rossini PM. Influencing poststroke plasticity with electromagnetic brain stimulation: Myth or reality? Neurology 2010; E-pub 2010 Nov. 10.