Cortical somatosensory processing after botulinum toxin therapy in post-stroke spasticity.

ABSTRACT: In dystonic and spastic movement disorders, abnormalities of motor control and somatosensory processing as well as cortical modulations associated with clinical improvement after botulinum toxin A (BoNT-A) treatment have been reported, but electrophysiological evidence remains controversial. In the present observational study, we aimed to uncover central correlates of post-stroke spasticity (PSS) and BoNT-A-related changes in the sensorimotor cortex by investigating the cortical components of somatosensory evoked potentials (SEPs). Thirty-one chronic stroke patients with PSS of the upper limb were treated with BoNT-A application into the affected muscles and physiotherapy. Clinical and electrophysiological evaluations were performed just before BoNT-A application (W0), then 4 weeks (W4) and 11 weeks (W11) later. PSS was evaluated with the modified Ashworth scale (MAS). Median nerve SEPs were examined in both upper limbs with subsequent statistical analysis of the peak-to-peak amplitudes of precentral P22/N30 and postcentral N20/P23 components. At baseline (W0), postcentral SEPs were significantly lower over the affected cortex. At follow up, cortical SEPs did not show any significant changes attributable to BoNT-A and/or physiotherapy, despite clear clinical improvement. Our results imply that conventional SEPs are of limited value in evaluating cortical changes after BoNT-A treatment and further studies are needed to elucidate its central actions.

Contemporary clinical neurophysiology applications in dystonia.

The complex phenomenological understanding of dystonia has transcended from the clinics to genetics, imaging and neurophysiology. One way in which electrophysiology will impact into the clinics are cases wherein a dystonic clinical presentation may not be typical or a "forme fruste" of the disorder. Indeed, the physiological imprints of dystonia are present regardless of its clinical manifestation. Underpinnings in the understanding of dystonia span from the peripheral, segmental and suprasegmental levels to the cortex, and various electrophysiological tests have been applied in the course of time to elucidate the origin of dystonia pathophysiology. While loss of inhibition remains to be the key finding in this regard, intricacies and variabilities exist, thus leading to a notion that perhaps dystonia should best be gleaned as network disorder. Interestingly, the complex process has now spanned towards the understanding in terms of networks related to the cerebellar circuitry and the neuroplasticity. What is evolving towards a better and cohesive view will be neurophysiology attributes combined with structural dynamic imaging. Such a sound approach will significantly lead to better therapeutic modalities in the future.

Somatosensory cortical activation in cervical dystonia and its modulation with botulinum toxin: an fMRI study.

Converging data on focal dystonias suggest a widespread disorder of somatosensory processing. The aims of our study were, first, to assess somatosensory activation patterns in cervical dystonia (CD) beyond the representation of the affected body parts and, second, to search for task-related activation changes induced by botulinum toxin type-A (BoNT-A) therapy. Functional magnetic resonance imaging (MRI) during electrical median nerve stimulation was employed in seven CD patients and nine controls; the examination was repeated 4 weeks after BoNT-A application to dystonic neck muscles. The pretreatment activation map of patients showed activation in the contralateral primary somatosensory cortex, but missing activation in the secondary somatosensory cortex and insula, in contrast to controls and patients after treatment. Clinically significant effect of BoNT-A therapy was associated with a significant increase of BOLD response in the contralateral secondary somatosensory, insular, and inferior parietal cortices. The posttreatment somatosensory maps of patients did not significantly differ from controls. This study has brought evidence of widespread disruption of somatosensory processing in CD and its modification with BoNT-A therapy.

The role of the cerebellum in 'real' and 'imaginary' line bisection explored with 1-Hz repetitive transcranial magnetic stimulation.

The role of the cerebellum is well characterized for many motor processes and for some cognitive tasks, although its contribution to lateralized spatial judgement has never been probed directly. To address this omission, we investigated the effects of cerebellar disruption on two different line bisection tasks in eight healthy subjects. Based on previous evidence of crossed cerebellar-cortical connections we predicted a shift in the perceived midline that would occur in opposite directions depending on the cerebellar hemisphere targeted. Repetitive transcranial magnetic stimulation (rTMS), given at 1-Hz (600 pulses), was used as a non-invasive way to interfere with processing in the cerebellar cortex. Performance was assessed for both 'physical' line bisection using a newly developed Landmark variant task and for 'mental' line bisection using number pairs. The effects for number line bisection were lateralized--left but not right cerebellar rTMS increased rightward errors, whereas for physical line bisection rTMS to either hemisphere did not affect performance. Effects due to neck muscle contraction and changes in eye position were ruled out with appropriate control stimulation sites, and eye-tracking. The results confirm the role of the cerebellum in spatial judgement, and, for the first time, demonstrate direct cerebellar involvement in the generation of the midline in 'imaginal' (number) space. The difference between number line and physical line bisection effects is discussed with reference to pre-existing models of cerebellar hemispheric specialization and functional topography.

Sensorimotor network in cervical dystonia and the effect of botulinum toxin treatment: a functional MRI study.

BACKGROUND: The evidence suggests that the origin of primary dystonia is at least partly associated with widespread dysfunction of the basal ganglia and cortico-striato-thalamo-cortical circuits. The aim of the study was to assess the sensorimotor activation pattern outside the circuits controlling the affected body part in cervical dystonia, as well as to determine task-related activation changes induced by botulinum toxin type A (BoNT-A) treatment. METHODS: Seven patients suffering from cervical dystonia and nine healthy controls were examined with functional MRI during skilled hand motor task; the examination was repeated 4 weeks after BoNT-A application to dystonic neck muscles. RESULTS: Functional MRI data demonstrated overall reduced extent of hand movement-related cortical activation but greater magnitude of blood oxygenation level dependent signal change in the contralateral secondary somatosensory cortex in patients compared to controls. Effective BoNT-A treatment led to reduced activation of the ipsilateral supplementary motor area and dorsal premotor cortex in patients. The patients' post-treatment sensorimotor maps showed significantly smaller basal ganglia activation compared to controls. CONCLUSIONS: These results provide imaging evidence that abnormalities in sensorimotor activation extend beyond circuits controlling the affected body parts in cervical dystonia. The study also supports observations that BoNT-A effect has a correlate at central nervous system level, and such effect may not be limited to cortical and subcortical representations of the treated muscles.

Cortical plasticity and its implications for focal hand dystonia.

BACKGROUND: The exact origin of focal dystonias has not been elucidated so far. Aberrant plasticity of the brain cortex is suspected to be a crucial factor in the development of this group of movement disorders. The aim of this article is to summarize recent findings on the etiopathogenesis of focal hand dystonias with a focus on the role of abnormal cortical plasticity. METHODS AND RESULTS: A search of the literature mainly from 1995 to 2005 was done using the PubMed and Ovid search engines. English-language articles were identified using the following keywords: focal hand dystonia or writer's cramp and cortical plasticity, sensorimotor, imaging. Additional references were found through bibliography reviews of relevant articles. The data from neurophysiological and imaging studies, as well as clinical observation, in focal hand dystonia suggest multiple failures at different levels of the somatosensory and motor systems, particularly in the brain cortex. This disorders lead to attenuation of inhibitory and fortification of excitatory processes. CONCLUSIONS: The emerging theory presumes that a maladaptive plasticity of brain cortex with abnormal sensorimotor intergration can evolve in predisposed individuals. Consequent methods of management of focal hand dystonias are outlined.