[Drugs for improvement of motor deficits after stroke]. / Pharmaka zur Verbesserung motorischer Defizite nach einem Schlaganfall.

Randomized controlled trials with a variety of drugs have been performed for approximately 20 years in order to support functional restitution of motor deficits after a stroke. Nowadays, serotonin reuptake inhibitors show the highest level of evidence due to the largest number of positive studies and L­dopa also seems to be effective; however, much fewer studies have been conducted. In the majority of trials amphetamines provided no additional benefits and D­cycloserine cannot be recommended either. Future therapeutic approaches, e.g. anti-nogo antibodies and cell therapy are presented.

[New aspects of neurorehabilitation: motor and language]. / Neues zur Neurorehabilitation: Motorik und Sprache.

Advancements in medical care over the last decades have contributed to a continuous decline in immediate post-stroke mortality. The flipside of this development is that patients surviving the initial stroke are forced to live with sometimes extreme functional motor and/or language limitations for the remaining life span. The following overview presents evidence-based neurorehabilitative interventions to promote motor and language recovery in the acute and chronic post-stroke stages. Therapeutic approaches comprise intensive training, neuropharmacological drugs and non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) or direct current stimulation (tDCS). Additionally, an outlook on promising future interventions for stroke neurorehabilitation is provided.

[Neurofeedback-based motor imagery training for rehabilitation after stroke]. / Neurofeedback-gestütztes Bewegungsvorstellungstraining zur Rehabilitation nach einem Schlaganfall.

Mental training, including motor observation and motor imagery, has awakened much academic interest. The presumed functional equivalence of motor imagery and motor execution has given hope that mental training could be used for motor rehabilitation after a stroke. Results obtained from randomized controlled trials have shown mixed results. Approximately half of the studies demonstrate positive effects of motor imagery training but the rest do not show an additional benefit. Possible reasons why motor imagery training has so far not become established as a robust therapeutic approach are discussed in detail. Moreover, more recent approaches, such as neurofeedback-based motor imagery or closed-loop systems are presented and the potential importance for motor learning and rehabilitation after a stroke is discussed.

[Polymorphism of brain derived neurotrophic factor and recovery of functions after ischemic stroke]. / Polymorphismus des "brain derived neurotrophic factor" und Erholung nach Schlaganfall.

BACKGROUND: After ischemic stroke, many factors influence the restitution of functions. In particular they include the patient age, the initial stroke severity and the presence of cognitive and neuropsychological deficits. In this study we investigated whether a polymorphism in the gene encoding for brain derived neurotrophic factor (BDNF) influences improvements of motor functions and everyday activities. METHODS: Patients with subacute ischemic stroke (n = 67) were examined at the beginning of an inpatient neurological rehabilitation, after 4 weeks of treatment and after 6 months. The Barthel index (BI) and the Rivermead motor assessment (RMA) were used to measure motor functions and everyday activities. Patients were allocated to three groups (valine [Val]/valine, val/methionine [Met] and Met/Met) depending on the BDNF polymorphism at codon 66. RESULTS: The 3 groups (Val/Val, n = 34 patients, Val/Met, n = 26 and Met/Met, n = 7) showed significant improvements in BI and RMA after 4 weeks and after 6 months as compared to the preceding measurements. The BI and RMA were positively correlated. The three groups did not differ with respect to the extent of improvement. CONCLUSION: After ischemic stroke, motor functions and everyday activities improved continuously over a period of at least 6 months. The BDNF polymorphism did not influence this development.

Clinical neurophysiology of functional motor disorders: IFCN Handbook Chapter.

Functional Motor Disorders are common and disabling. Clinical diagnosis has moved from one of exclusion of other causes for symptoms to one where positive clinical features on history and examination are used to make a "rule in" diagnosis wherever possible. Clinical neurophysiological assessments have developed increasing importance in assisting with this positive diagnosis, not being used simply to demonstrate normal sensory-motor pathways, but instead to demonstrate specific abnormalities that help to positively diagnose these disorders. Here we provide a practical review of these techniques, their application, interpretation and pitfalls. We also highlight particular areas where such tests are currently lacking in sensitivity and specificity, for example in people with functional dystonia and functional tic-like movements.

Motor imagery in stroke patients, or plegic patients with spinal cord or peripheral diseases.

OBJECTIVES: When motor imagery (MI) is impaired in stroke patients, it is not clear, whether this is caused by the central lesion with a disruption of networks or this may be due to inactivity/lack of practice following hemiparesis. To answer this question, we investigated MI in two groups of patients: stroke patients and patients with no central lesion, who suffered high-grade tetraparesis caused by myopathy or spinal muscular atrophy. MATERIALS AND METHODS: The first study measured MI in 31 sub-acute and chronic stroke patients with hand paresis. We used self-assessment questionnaires [Kinaesthetic and Visual Imagery Questionnaire (KVIQ), the Vividness of Motor Imagery Questionnaire (VMIQ)] as well as a new chronometric test (mental version and normal/physical version of Box and Block Test). The second study assessed MI in 10 patients without a central lesion, but with severe tetraparesis of peripheral origin. They were incapable of performing the requested task physically. RESULTS: MI in patients was better (i) for the third-person (VMIQ(3.P) ) compared to the first-person perspective (VMIQ(1.P) ), (ii) in patients without sensory impairment compared to those with impaired proprioception, (iii) in patients with light paresis compared to severe paresis and (iv) for the non-affected than the affected hand (KVIQ-10). Patients with severe tetraparesis were able to imagine another person's knee bends, but were not capable of imagining themselves performing knee bends. CONCLUSIONS: MI may be hampered on the affected side in severely paretic patients, particularly in the presence of impaired proprioception. Remarkably, the second study illustrates that motor experiences shape MI. This confirms the close relationship between MI and movement execution. The study advocates the careful use of test batteries for assessment of MI when investigating mental training in clinical trials. Not all patients might benefit to the same extent from MI training. This is possibly contingent on intact proprioception and preserved MI.

[Evidence-based methods in motor rehabilitation after stroke]. / Evidenzbasierte Verfahren in der motorischen Rehabilitation nach Schlaganfall.

In this review, treatments for motor rehabilitation after stroke will be presented. In particular, randomised, controlled trials, meta-analyses and systematic reviews, mainly from the years 2009 - 2011, were taken into consideration. In summary, evidence is best for constraint-induced movement therapy and Botulinum toxin type A in patients with focal spasticity. Superiority has been demonstrated for the administration of drugs (serotonin re-uptake inhibitors and L-dopa), mirror therapy, the use of virtual reality, electromechanical devices to restore independent walking, and fitness and circuit training. Other therapies (bilateral arm training, treadmill therapy, robot-assisted arm therapy) did not show superiority. For sensory training and repetitive transcranial magnetic stimulation large clinical studies still need to be done.

No effect of a levodopa single dose on motor performance and motor excitability in chronic stroke. A double-blind placebo-controlled cross-over pilot study.

PURPOSE: Drugs that modulate neuronal transmission can influence motor recovery after stroke. Here, we tested if a single dose of levodopa could improve motor functions and change motor excitability in a group of chronic stroke patients. METHODS: Ten patients > 6 months after their stroke participated in a placebo-controlled double-blind trial. On two different occasions, they received either 100 mg levodopa or placebo in a randomized order. After drug intake, they participated in one hour of physiotherapy aimed at an improvement of dexterity. Motor functions were tested by application of the Nine-Hole-Peg Test, a dynamometer measuring grip strength and the Action Research Arm Test. In addition, transcranial magnetic stimulation (TMS) was applied to study intracortical excitability, stimulus response curves and silent periods. TMS studies and motor function measurements were performed before drug intake, 45 minutes after drug ingestion and after the physiotherapy. RESULTS: Compared to placebo, levodopa neither improved motor functions nor changed motor excitability as tested by TMS. CONCLUSION: These findings suggests that a single levodopa dose is not sufficient to improve motor function in chronic stroke. However, it cannot be excluded that the lack of a beneficial effect is related to the small study sample.

Acupuncture treatment improves nerve conduction in peripheral neuropathy.

The etiology of peripheral neuropathy (PN) often remains elusive resulting in a lack of objective therapeutic strategies. We conducted a pilot study to evaluate the therapeutic effect of acupuncture on PN as measured by changes in nerve conduction and assessment of subjective symptoms. One hundred and ninety-two consecutive patients with PN as diagnosed by nerve conduction studies (NCS) were evaluated over a period of 1 year. Of 47 patients who met the criteria for PN of undefined etiology, 21 patients received acupuncture therapy according to classical Chinese Medicine as defined by the Heidelberg Model, while 26 patients received the best medical care but no specific treatment for PN. Sixteen patients (76%) in the acupuncture group improved symptomatically and objectively as measured by NCS, while only four patients in the control group (15%) did so. Three patients in the acupuncture group (14%) showed no change and two patients an aggravation (10%), whereas in the control group seven showed no change (27%) and 15 an aggravation (58%). Importantly, subjective improvement was fully correlated with improvement in NCS in both groups. The data suggest that there is a positive effect of acupuncture on PN of undefined etiology as measured by objective parameters.

Influence of cabergoline on motor excitability in patients with restless legs syndrome.

To investigate whether the increased urge to move the legs in restless legs syndrome (RLS) corresponds to an electrophysiological phenomenon and whether motor excitability or behavior is influenced by the treatment with a dopamine agonist. We examined 10 patients who had RLS with transcranial magnetic stimulation (TMS) before and during treatment with the dopamine agonist cabergoline. Results were compared with data obtained from healthy subjects. Inhibitory mechanisms were explored by measurement of the cortical silent period (cSP). Recordings were obtained from the right anterior tibial muscle. Clinical severity of RLS was rated using the International Restless Legs Syndrome Study Group Rating Scale (IRLSSGRS). During therapy with cabergoline, all patients reported a significant improvement of RLS symptoms. Before medication, patients showed a significant shortening of cSP compared with healthy subjects. After 14 days of treatment with cabergoline, cSP normalized in RLS patients; 90 days after the start of daily cabergoline, cSP tended to shorten again, whereas RLS symptoms further improved. There was no correlation between cSP duration and IRLSSGRS results. There were no differences in patient and control motor thresholds. These thresholds remained unchanged during treatment with cabergoline. RLS patients have a disturbance of inhibitory neurons that can temporarily be reversed with a dopamine agonist. However, the cSP does not correlate with the clinical symptoms.

Motor cortex excitability after thalamic infarction.

OBJECTIVE: We examined 8 patients with hemihypesthesia due to an ischemic thalamic lesion to explore the effects of a central sensory dysfunction on motor cortex excitability. METHODS: Motor excitability was assessed using transcranial magnetic stimulation techniques and electrical peripheral nerve stimulation. Motor function was evaluated by the Nine-Hole-Peg Test and measurement of hand grip strength. The affected side was compared with the non-lesioned side and with an age-matched control group. RESULTS: Patients had a loss of inhibition and an increase of facilitation in the motor cortex of the affected side. The silent period was prolonged and motor function was impaired on the affected side. CONCLUSIONS: A thalamic lesion can modulate motor cortical excitability. SIGNIFICANCE: This study suggests that, under normal conditions, somatosensory afferents influence inhibitory and excitatory properties in the motor cortex.

Transcranial magnetic stimulation in neurorehabilitation.

In neurorehabilitation, transcranial magnetic stimulation (TMS) offers information regarding prognosis and pathophysiology and could also be useful for therapeutic purposes. Numerous studies have indicated that, after stroke, the absence of motor evoked potentials is associated with a poor motor recovery. In contrast, MEPs obtained in the paretic muscle with low stimulus intensities suggest a good restitution of motor function. TMS studies have shown that the location of a brain lesion determines motor cortex excitability changes: Patients with central somatosensory lesions show a disinhibition in the ipsilesional motor cortex. Lesions in the territory of the superior cerebellar artery are associated with a loss of motor cortex excitability. Stroke patients participating in a Constraint-induced movement therapy show an enlargement of the motor output area in the affected hemisphere after therapy. This enhancement of motor excitability is associated with an improvement of motor function. Some evidence is emerging that the application of low frequency repetitive TMS over the non-lesioned hemisphere improves neglect phenomena by down-regulation of the excitability of the non-lesioned hemisphere.

Motor cortex excitability after cerebellar infarction.

BACKGROUND AND PURPOSE: The cerebellum has an influence on motor excitability. We investigated if the location of a cerebellar infarction was crucial for changes of motor cortex excitability and if the electrophysiological findings were correlated with motor performance. METHODS: Transcranial magnetic stimulation was applied to study intracortical inhibition (ICI), intracortical facilitation (ICF), motor thresholds, and corticospinal excitability. Dexterity as a measure of motor performance was tested with the Nine-Hole-Peg Test (9HPT). Ratios (affected/unaffected) were also calculated. RESULTS: ICI and ICF ratios were negatively correlated with 9HPT ratios in all patients (n=9). Compared with an age-matched control group, patients with lesions in the territory of the superior cerebellar artery (SCA) (n=3) or a lesion rostral of the dentate nucleus (n=1) had abnormally enhanced ICI and a loss of ICF (3 patients). Dexterity was impaired in all 4 patients. Motor excitability and motor performance normalized over the subsequent weeks. Patients with an infarct either in the territory of the anterior inferior cerebellar artery (n=2) or in the territory of the posterior inferior cerebellar artery (n=3) displayed motor excitability and motor performance within the normal range. CONCLUSIONS: The superior part of the cerebellum has a strong influence on motor cortex excitability. We suggest that the enhancement of motor inhibition and reduction of motor facilitation is mediated by an impairment of the deep cerebellar nuclei.

Lesion-induced and training-induced brain reorganization.

INTRODUCTION: A stroke may modulate motor cortex excitability. We examined if distinct ischemic brain lesions are associated with a specific pattern of excitability changes. We also investigated the effects of a rehabilitative therapy on motor excitability. METHODS: In stroke patients, the consequences of a) a lesion in the central somatosensory system, b) a cerebellar lesion and c) a two week period of Constraint-induced movement therapy (CIMT), on motor cortex excitability were studied. Transcranial magnetic stimulation techniques and functional magnetic resonance imaging (fMRI) were employed. RESULTS: Patients with a lesion in the primary somatosensory cortex or in the ventroposterolateral nucleus of the thalamus had a decreased intracortical inhibition on the affected side. Patients with lesions in the territory of the superior cerebellar artery had a loss of intracortical facilitation and an increase of intracortical inhibition. Patients with cortical lesions undergoing CIMT had a loss of intracortical inhibition prior to therapy. After CIMT, changes of ICI were stronger in the lesioned than in the non-lesioned hemisphere but could result either in an increase of ICI or a reduction of ICI. In three patients fMRI results showed that cortical activation was less post CIMT as compared to pre-treatment activation. In parallel, ICI was reduced after treatment. CONCLUSIONS: Our results suggest that, physiologically, central somatosensory influence on the motor cortex is inhibitory. In contrast, the cerebellum normally exerts a facilitatory influence on the motor cortex. CIMT induces changes of intracortical excitability mainly in the affected hemisphere.

Effects of passive tactile co-activation on median ulnar nerve representation in human SI.

In animals simple passive co-activation causes a fusion and expansion of the involved cortical representations. We used passive tactile finger co-activation for 40 min to investigate cortical representational changes in the human somatosensory cortex. Magnetic source imaging revealed that the euclidean distance between median and ulnar nerve somatosensory evoked fields (SEF) was significantly reduced after application of 600 synchronous airpuff stimuli to the fingertips of four fingers. In the control experiment without co-activation no significant change in distance was observed. Perception threshold and spatial two-point discrimination were not affected by the synchronous stimulation. This is in contrast to blind three-finger Braille readers who frequently mislocalize stimuli applied to the reading fingers. This points to a lack of behavioural relevance or the short duration of co-activation.

Structural and functional cortical abnormalities after upper limb amputation during childhood.

Functional reorganization has been well documented in the human adult brain after amputation of the arm. To assess the effects of amputation on the developing brain, we investigated six patients with upper limb amputation in early childhood and one with right dysmelia. Transcranial magnetic stimulation indicated contralateral cortical disinhibition and enlargement of the excitable area of the stump. FMRI data corroborated these plastic changes and also showed an ipsilateral functional reorganization. In the T1-weighted MRI, we found structural deformities of the contralateral and ipsilateral central sulcus in three patients and a contralateral atrophic parietal lobule in two patients. Therefore, arm amputation in childhood affects functional organization as well as anatomical structure in both hemispheres.

The influence of lorazepam on somatosensory-evoked fast frequency (600 Hz) activity in MEG.

The generators of high frequency bursts (600-Hz activity) detected at the parietal scalp over the primary somatosensory cortex after electrical stimulation of peripheral nerves are not yet known. We investigated the influence of benzodiazepine on the somatosensory-evoked 600-Hz activity by means of neuromagnetic measurements and source analysis. After oral administration of lorazepam, the latency of the 600-Hz burst activity was increased; specifically later peaks were delayed more than earlier peaks. In contrast, the latency of the concurrent primary cortical low frequency response (N20m) was not significantly changed. The source strengths of both N20m and 600-Hz bursts were significantly increased. Our results provide evidence for two components of the 600-Hz activity with a different generator structure.

Motor cortex plasticity during forced-use therapy in stroke patients: a preliminary study.

Treatment-induced plastic changes were investigated in the brains of stroke patients in the subacute stage of illness. Nine patients participated in 1 week of conventional physiotherapy. In the subsequent week conventional physiotherapy was combined with forced-use therapy. Focal transcranial magnetic stimulation was used to determine the motor output areas of the abductor pollicis brevis muscles prior to the treatment and after the first and after the second week. Motor performance was evaluated using the Nine Hole Peg Test, the Frenchay Arm Test and vigorometry to measure the grip strength. Before treatment the cortical representation area of the paretic hand muscle was significantly smaller than the contralateral side. This difference persisted after the first week of physiotherapy. In contrast, the motor output map in the affected hemisphere was significantly enlarged after forced-use therapy. This increase in motor cortex excitability was accompanied by a significant improvement in dexterity. Across the two treatment weeks the centres of the motor output maps shifted significantly stronger in the affected hemisphere than in unaffected hemisphere, suggesting the recruitment of adjacent brain areas. We conclude that the combination of forced-use therapy and conventional physiotherapy enhances motor cortex excitability and improves motor performance compared to a preceding conventional physiotherapy alone. Due to the small number of patients and the lack of a control group, these results are preliminary observations and require replication in a larger sample.

Inhibition of ipsilateral motor cortex during phasic generation of low force.

OBJECTIVE: To study the effect of different types of unilateral pinch grips on excitability of the ipsilateral motor cortex. METHODS: In 9 healthy volunteers, transcranial magnetic stimuli (TMS) were applied over one motor cortex while the subjects performed either phasic or tonic ipsilateral pinch grips with different force levels (range 1-40% maximum voluntary contraction, MVC). Motor evoked potentials (MEP) were recorded from the relaxed contralateral first dorsal interosseous muscle (FDI) and were compared to MEPs obtained during muscle relaxation of both hands. In additional experiments, transcranial electrical stimuli (TES) were administered and F waves were recorded after electrical stimulation of the ulnar nerve. RESULTS: Phasic pinch grips with low force (1 and 2% MVC) induced a significant decrease of TMS-induced MEP amplitudes. The effect lasted for about 100 ms after reaching the force level and was similar for both right and left-handed pinch grips. TES-induced MEPs and F waves remained unchanged. In contrast, tonic contractions (20 and 40% MVC) enhanced MEPs in the homologous FDI. CONCLUSIONS: Phasic pinch grips with low force inhibit the motor cortex responsible for the contralateral homologous hand muscle. This effect, which is probably mediated transcallosally, might act at the level of the motor cortex.

Disinhibition of somatosensory and motor cortex in mitochondriopathy without myoclonus.

OBJECTIVE: To test electrophysiologically, if patients with mitochondriopathy but without evidence of myocloni have subclinical signs of disinhibition in motor and somatosensory cortices. METHODS: Two patients were studied and compared with age-matched control groups. RESULTS: In both patients, giant somatosensory evoked potentials after median nerve stimulation and a reduced intracortical inhibition tested by transcranial magnetic stimulation in a paired pulse paradigm indicated a dysfunction of inhibitory circuits in the motor as well as the somatosensory cortex. In addition, the somatosensory evoked 600 Hz activity recorded by magnetoencephalography was abolished. CONCLUSIONS: Patients with mitochondriopathy may suffer from a subclinical disturbance of inhibition in the sensorimotor cortex. The loss of 600 Hz activity indicates that these high-frequency oscillations could reflect the activity of inhibitory neurons in the somatosensory cortex.