Noninvasive Brain Stimulation May Spur Stroke Recovery

CHICAGO—Noninvasive brain stimulation may potentiate rehabilitation training in patients with stroke, according to an overview presented at the 140th Annual Meeting of the American Neurological Association. Heidi Schambra, MD, Assistant Professor of Neurology at Columbia University in New York, described two types of stimulation that hold promise as adjuvants in stroke recovery—repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Large trials of those interventions in patients with stroke are expected to be completed next year.

“To date, the clinical effects seen with noninvasive brain stimulation are modest, but promising,” said Dr. Schambra. “The field of noninvasive brain stimulation is still relatively young, and work is currently under way to identify stimulation parameters that optimize behavioral gains.” The stimulation methods appear to have excellent safety and tolerability profiles and “may well become part of routine clinical treatment in recovering stroke patients,” she said.

Post-Stroke Plasticity

The weeks after stroke are believed to be a critical period of neuroplasticity. Studies suggest, however, that patients may not perform enough repetitions during training sessions to achieve the greatest functional gains. “We’re underdosing our patients probably by an order of magnitude,” Dr. Schambra said. “They’re really not getting that degree of repetition that’s necessary to engender that activity-dependent plasticity.”

As a consequence, researchers hope to identify interventions that amplify activity-dependent plasticity driven by training therapies. Both tDCS and rTMS are painless and produce prolonged changes in cortical excitability, with aftereffects that last between 20 and 40 minutes. “Importantly, both [treatments] must be given in conjunction with physical or cognitive training to yield behavioral improvement,” said Dr. Schambra. While other types of noninvasive stimulation with longer aftereffects (eg, theta-burst stimulation and quadripulse stimulation) may prove beneficial, rTMS and tDCS have been studied the most in clinical settings, she added.

Restoring Inhibitory Balance

Research has suggested that the nonlesioned hemisphere excessively inhibits the lesioned hemisphere following stroke. To restore interhemispheric inhibitory balance, rTMS is used to diminish excitability in the nonlesioned hemisphere or to increase excitability in the lesioned hemisphere. The stimulation is believed to briefly reset the balance and promote the consolidation of motor skill learning.

In a study of rTMS in patients with ischemic stroke that was conducted in Egypt, Eman Khedr, MD, and colleagues randomized 36 patients to 1 Hz (ie, inhibitory) rTMS over the nonlesioned hemisphere, 3 Hz (ie, excitatory) rTMS over the lesioned hemisphere, or sham stimulation. Patients received stimulation daily for five days. Patients also received occupational therapy. Both types of stimulation were effective in improving scores on the pegboard task and Barthel scale, compared with sham stimulation. In addition, researchers found that 1 Hz rTMS over the nonlesioned hemisphere was more effective than 3 Hz rTMS over the lesioned hemisphere. The results persisted at three months. “The gains brought about by training with occupational therapy in the post-stimulated state were a good starting point, and that was improved upon in the months following,” said Dr. Schambra.

Although early studies have been small, a large phase III trial sponsored by Nexstim is under way. The Navigated Inhibitory rTMS to Contralesional Hemisphere (NICHE) trial is an ongoing multicenter, randomized, controlled, double-blind study comparing 1 Hz rTMS and sham rTMS in patients with post-stroke motor impairment. The upper extremity Fugl-Meyer Assessment, an assay of motor impairment, is the primary outcome. Results from the NICHE trial could be reported by the end of next year.

Direct-Current Stimulation

Of all electrical stimulation approaches, tDCS is the most common. It uses a low-intensity constant current passed from an anodal to a cathodal electrode. Evidence suggests that the current flows throughout the brain, that the stimulation preferentially modulates networks that are active during stimulation, and that tDCS facilitates long-term potentiation, said Dr. Schambra.

In a study conducted by Dr. Schambra and colleagues, groups of 12 subjects used a force transducer to control a cursor on a screen. Subjects were trained for five days, during which time they received sham stimulation or tDCS over the primary motor cortex opposite the training hand. The investigators found that the skill level of subjects who received anodal stimulation showed greater improvement over time, relative to sham tDCS and to cathodal stimulation. The differences persisted after three months. In addition, all groups experienced the same rate of decay in skill level over time. This finding indicates that the learning enhancement with anodal stimulation follows the same principles of skill acquisition and decay as normal learning, but the magnitudes are amplified, Dr. Schambra said. The researchers conducted the same experiment in patients with chronic stroke and had the same results.

Investigators plan to evaluate tDCS further in a large, multicenter clinical trial in Europe. The Neuroregeneration Enhanced by tDCS in Stroke (NETS) trial will compare anodal stimulation of the lesioned hemisphere versus sham stimulation in the subacute phase of first-ever stroke. Both interventions will be combined with functional training. The upper extremity Fugl-Meyer Assessment is the primary outcome. The trial is expected to complete by the end of 2016.

Future studies will aim to further understand the optimal stimulation parameters for these types of stimulation, and to identify which patients with stroke are appropriate for these interventions, Dr. Schambra said.

—Jake Remaly

CHICAGO—Noninvasive brain stimulation may potentiate rehabilitation training in patients with stroke, according to an overview presented at the 140th Annual Meeting of the American Neurological Association. Heidi Schambra, MD, Assistant Professor of Neurology at Columbia University in New York, described two types of stimulation that hold promise as adjuvants in stroke recovery—repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Large trials of those interventions in patients with stroke are expected to be completed next year.

“To date, the clinical effects seen with noninvasive brain stimulation are modest, but promising,” said Dr. Schambra. “The field of noninvasive brain stimulation is still relatively young, and work is currently under way to identify stimulation parameters that optimize behavioral gains.” The stimulation methods appear to have excellent safety and tolerability profiles and “may well become part of routine clinical treatment in recovering stroke patients,” she said.

Post-Stroke Plasticity

The weeks after stroke are believed to be a critical period of neuroplasticity. Studies suggest, however, that patients may not perform enough repetitions during training sessions to achieve the greatest functional gains. “We’re underdosing our patients probably by an order of magnitude,” Dr. Schambra said. “They’re really not getting that degree of repetition that’s necessary to engender that activity-dependent plasticity.”

As a consequence, researchers hope to identify interventions that amplify activity-dependent plasticity driven by training therapies. Both tDCS and rTMS are painless and produce prolonged changes in cortical excitability, with aftereffects that last between 20 and 40 minutes. “Importantly, both [treatments] must be given in conjunction with physical or cognitive training to yield behavioral improvement,” said Dr. Schambra. While other types of noninvasive stimulation with longer aftereffects (eg, theta-burst stimulation and quadripulse stimulation) may prove beneficial, rTMS and tDCS have been studied the most in clinical settings, she added.

Restoring Inhibitory Balance

Research has suggested that the nonlesioned hemisphere excessively inhibits the lesioned hemisphere following stroke. To restore interhemispheric inhibitory balance, rTMS is used to diminish excitability in the nonlesioned hemisphere or to increase excitability in the lesioned hemisphere. The stimulation is believed to briefly reset the balance and promote the consolidation of motor skill learning.

In a study of rTMS in patients with ischemic stroke that was conducted in Egypt, Eman Khedr, MD, and colleagues randomized 36 patients to 1 Hz (ie, inhibitory) rTMS over the nonlesioned hemisphere, 3 Hz (ie, excitatory) rTMS over the lesioned hemisphere, or sham stimulation. Patients received stimulation daily for five days. Patients also received occupational therapy. Both types of stimulation were effective in improving scores on the pegboard task and Barthel scale, compared with sham stimulation. In addition, researchers found that 1 Hz rTMS over the nonlesioned hemisphere was more effective than 3 Hz rTMS over the lesioned hemisphere. The results persisted at three months. “The gains brought about by training with occupational therapy in the post-stimulated state were a good starting point, and that was improved upon in the months following,” said Dr. Schambra.

Although early studies have been small, a large phase III trial sponsored by Nexstim is under way. The Navigated Inhibitory rTMS to Contralesional Hemisphere (NICHE) trial is an ongoing multicenter, randomized, controlled, double-blind study comparing 1 Hz rTMS and sham rTMS in patients with post-stroke motor impairment. The upper extremity Fugl-Meyer Assessment, an assay of motor impairment, is the primary outcome. Results from the NICHE trial could be reported by the end of next year.

Direct-Current Stimulation

Of all electrical stimulation approaches, tDCS is the most common. It uses a low-intensity constant current passed from an anodal to a cathodal electrode. Evidence suggests that the current flows throughout the brain, that the stimulation preferentially modulates networks that are active during stimulation, and that tDCS facilitates long-term potentiation, said Dr. Schambra.

In a study conducted by Dr. Schambra and colleagues, groups of 12 subjects used a force transducer to control a cursor on a screen. Subjects were trained for five days, during which time they received sham stimulation or tDCS over the primary motor cortex opposite the training hand. The investigators found that the skill level of subjects who received anodal stimulation showed greater improvement over time, relative to sham tDCS and to cathodal stimulation. The differences persisted after three months. In addition, all groups experienced the same rate of decay in skill level over time. This finding indicates that the learning enhancement with anodal stimulation follows the same principles of skill acquisition and decay as normal learning, but the magnitudes are amplified, Dr. Schambra said. The researchers conducted the same experiment in patients with chronic stroke and had the same results.

Investigators plan to evaluate tDCS further in a large, multicenter clinical trial in Europe. The Neuroregeneration Enhanced by tDCS in Stroke (NETS) trial will compare anodal stimulation of the lesioned hemisphere versus sham stimulation in the subacute phase of first-ever stroke. Both interventions will be combined with functional training. The upper extremity Fugl-Meyer Assessment is the primary outcome. The trial is expected to complete by the end of 2016.

Future studies will aim to further understand the optimal stimulation parameters for these types of stimulation, and to identify which patients with stroke are appropriate for these interventions, Dr. Schambra said.

—Jake Remaly

CHICAGO—Noninvasive brain stimulation may potentiate rehabilitation training in patients with stroke, according to an overview presented at the 140th Annual Meeting of the American Neurological Association. Heidi Schambra, MD, Assistant Professor of Neurology at Columbia University in New York, described two types of stimulation that hold promise as adjuvants in stroke recovery—repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Large trials of those interventions in patients with stroke are expected to be completed next year.

“To date, the clinical effects seen with noninvasive brain stimulation are modest, but promising,” said Dr. Schambra. “The field of noninvasive brain stimulation is still relatively young, and work is currently under way to identify stimulation parameters that optimize behavioral gains.” The stimulation methods appear to have excellent safety and tolerability profiles and “may well become part of routine clinical treatment in recovering stroke patients,” she said.

Post-Stroke Plasticity

The weeks after stroke are believed to be a critical period of neuroplasticity. Studies suggest, however, that patients may not perform enough repetitions during training sessions to achieve the greatest functional gains. “We’re underdosing our patients probably by an order of magnitude,” Dr. Schambra said. “They’re really not getting that degree of repetition that’s necessary to engender that activity-dependent plasticity.”

As a consequence, researchers hope to identify interventions that amplify activity-dependent plasticity driven by training therapies. Both tDCS and rTMS are painless and produce prolonged changes in cortical excitability, with aftereffects that last between 20 and 40 minutes. “Importantly, both [treatments] must be given in conjunction with physical or cognitive training to yield behavioral improvement,” said Dr. Schambra. While other types of noninvasive stimulation with longer aftereffects (eg, theta-burst stimulation and quadripulse stimulation) may prove beneficial, rTMS and tDCS have been studied the most in clinical settings, she added.

Restoring Inhibitory Balance

Research has suggested that the nonlesioned hemisphere excessively inhibits the lesioned hemisphere following stroke. To restore interhemispheric inhibitory balance, rTMS is used to diminish excitability in the nonlesioned hemisphere or to increase excitability in the lesioned hemisphere. The stimulation is believed to briefly reset the balance and promote the consolidation of motor skill learning.

In a study of rTMS in patients with ischemic stroke that was conducted in Egypt, Eman Khedr, MD, and colleagues randomized 36 patients to 1 Hz (ie, inhibitory) rTMS over the nonlesioned hemisphere, 3 Hz (ie, excitatory) rTMS over the lesioned hemisphere, or sham stimulation. Patients received stimulation daily for five days. Patients also received occupational therapy. Both types of stimulation were effective in improving scores on the pegboard task and Barthel scale, compared with sham stimulation. In addition, researchers found that 1 Hz rTMS over the nonlesioned hemisphere was more effective than 3 Hz rTMS over the lesioned hemisphere. The results persisted at three months. “The gains brought about by training with occupational therapy in the post-stimulated state were a good starting point, and that was improved upon in the months following,” said Dr. Schambra.

Although early studies have been small, a large phase III trial sponsored by Nexstim is under way. The Navigated Inhibitory rTMS to Contralesional Hemisphere (NICHE) trial is an ongoing multicenter, randomized, controlled, double-blind study comparing 1 Hz rTMS and sham rTMS in patients with post-stroke motor impairment. The upper extremity Fugl-Meyer Assessment, an assay of motor impairment, is the primary outcome. Results from the NICHE trial could be reported by the end of next year.

Direct-Current Stimulation

Of all electrical stimulation approaches, tDCS is the most common. It uses a low-intensity constant current passed from an anodal to a cathodal electrode. Evidence suggests that the current flows throughout the brain, that the stimulation preferentially modulates networks that are active during stimulation, and that tDCS facilitates long-term potentiation, said Dr. Schambra.

In a study conducted by Dr. Schambra and colleagues, groups of 12 subjects used a force transducer to control a cursor on a screen. Subjects were trained for five days, during which time they received sham stimulation or tDCS over the primary motor cortex opposite the training hand. The investigators found that the skill level of subjects who received anodal stimulation showed greater improvement over time, relative to sham tDCS and to cathodal stimulation. The differences persisted after three months. In addition, all groups experienced the same rate of decay in skill level over time. This finding indicates that the learning enhancement with anodal stimulation follows the same principles of skill acquisition and decay as normal learning, but the magnitudes are amplified, Dr. Schambra said. The researchers conducted the same experiment in patients with chronic stroke and had the same results.

Investigators plan to evaluate tDCS further in a large, multicenter clinical trial in Europe. The Neuroregeneration Enhanced by tDCS in Stroke (NETS) trial will compare anodal stimulation of the lesioned hemisphere versus sham stimulation in the subacute phase of first-ever stroke. Both interventions will be combined with functional training. The upper extremity Fugl-Meyer Assessment is the primary outcome. The trial is expected to complete by the end of 2016.

Future studies will aim to further understand the optimal stimulation parameters for these types of stimulation, and to identify which patients with stroke are appropriate for these interventions, Dr. Schambra said.

—Jake Remaly