White Matter Integrity and Chronic Poststroke Upper Limb Function: An ENIGMA Stroke Recovery Analysis.

BACKGROUND: Integrity of the corticospinal tract (CST) is an important biomarker for upper limb motor function following stroke. However, when structurally compromised, other tracts may become relevant for compensation or recovery of function. METHODS: We used the ENIGMA Stroke Recovery data set, a multicenter, retrospective, and cross-sectional collection of patients with upper limb impairment during the chronic phase of stroke to test the relevance of tracts in individuals with less and more severe (laterality index of CST fractional anisotropy ≥0.25) CST damage in an observational study design. White matter integrity was quantified using fractional anisotropy for the CST, the superior longitudinal fascicle, and the callosal fibers interconnecting the primary motor cortices between hemispheres. Optic radiations served as a control tract as they have no a priori relevance for the motor system. Pearson correlation was used for testing correlation with upper limb motor function (Fugl-Meyer upper extremity). RESULTS: From 1235 available data sets, 166 were selected (by imaging, Fugl-Meyer upper extremity, covariates, stroke location, and stage) for analyses. Only individuals with severe CST damage showed a positive association of fractional anisotropy in both callosal fibers interconnecting the primary motor cortices (r[21]=0.49; P=0.025) and superior longitudinal fascicle (r[21]=0.51; P=0.018) with Fugl-Meyer upper extremity. CONCLUSIONS: Our data support the notion that individuals with more severe damage of the CST depend on residual pathways for achieving better upper limb outcome than those with less affected CST.

Interhemispheric parietal cortex connectivity reflects improvement in post-stroke spasticity due to treatment with botulinum toxin-A.

In post-stroke spasticity (PSS), effective treatment with botulinum neurotoxin (BoNT) is associated with transient decrease in activation of the ipsilesional superior parietal lobule (SPL) and intraparietal sulcus (IPS). We hypothesized that this would be reflected in changes in resting-state functional connectivity (rsFC) of the SPL/IPS. Our aim was therefore to assess rsFC of the ipsilesional SPL/IPS in chronic stroke patients with hemiparesis both with and without PSS and to explore the relationship between SPL/IPS rsFC and PSS severity. To this end, fourteen chronic stroke patients with upper limb weakness and PSS (the PSS group) and 8 patients with comparable weakness but no PSS (the control group) underwent clinical evaluation and 3 fMRI examinations, at baseline (W0) and 4 and 11 weeks after BoNT (W4 and W11, respectively). Seed-based rsFC of the atlas-based SPL and IPS was evaluated using a group×time interaction analysis and a correlation analysis with PSS severity (modified Ashworth scale), integrity of the ipsilesional somatosensory afferent pathway (evoked potential N20 latency), and age. In the PSS group, transient improvement in PSS was associated with increase in rsFC between the ipsilesional IPS and the contralesional SPL at W4. The interhemispheric connectivity was negatively correlated with PSS severity at baseline and with PSS improvement at W4. We propose adaptation of the internal forward model as the putative underlying mechanism and discuss its possible association with increased limb use, diminished spastic dystonia, or improved motor performance, as well as its potential contribution to the clinical effects of BoNT.

Polypharmacy in patients with multiple sclerosis and the impact on levels of care and therapy units.

Background: The aim of this study was to examine the societal costs of polypharmacy in patients with multiple sclerosis (MS). We therefore focused on the association between the number of medications on the level of care (LOC), the German classification of the need for care, and the number of therapy sessions (TTU). Methods: In addition to demographic information and medication, 101 MS patients performed the Multiple Sclerosis Health Resource Utilization Survey (MS-HRS). Medications were subdivided into a total number of medications (TD), MS-related medication [MSD, i.e., disease-modifying drugs (DMDs) and symptomatic treatment (SD)], and medication for comorbidities (CDs). Multivariate linear regression models were performed to estimate if the amount of each medication type affects LOC or TTU. Results: Polypharmacy appeared in 54 patients at the time of the survey. The relative risk (RR) of LOC 1 increased significantly by 2.46 (p = 0.001) per TD and by 2.55 (p = 0.004) per MSD, but not per CD (RR 1.44; p = 0.092). The effect of RR on MSD was driven by SD (RR 2.2; p = 0.013) but not DMD (RR 2.6; p = 0.4). RR of MSD remained significant for LOC 2 (1.77; p = 0.009) and LOC 3/4 (1.91; p = 0.015), with a strong trend in RR of SD, but not DMD. TTU increased significantly per MSD (p = 0.012), but not per TD (p = 0.081) and CD (p = 0.724). Conclusion: The number of MSDs is related to the likelihood of a higher level of care and the number of therapy sessions and is therefore a good indication of the extent of the societal costs.

Correlation between retinal oxygen saturation and the haemodynamic parameters of the ophthalmic artery in healthy subjects.

PURPOSE: The aim of the study was to obtain the values of oxygen saturation in retinal vessels and ophthalmic blood flow parameters in a healthy Caucasian population and assess whether the oximetry parameters are affected by the flow rate or the vascular resistance. METHODS: The spectrophotometric retinal oximetry and colour Doppler imaging (CDI) of retinal vessels were successfully performed with 52 healthy subjects (average age 29.7 ± 5.6 years). The retinal oximeter simultaneously measures the wavelength difference of haemoglobin oxygen saturation in retinal arterioles and venules. The arteriolar and venular saturation in both eyes was measured. The peak systolic (PSV) end diastolic (EDV) velocities, resistive (RI) and pulsatility (PI) indices were obtained for both eyes using CDI in the ophthalmic artery. A paired t-test and two sample t-tests were used for statistical analyses. The correlation was assessed using the Pearson coefficient correlation. RESULTS: The mean oxygen saturation level was 96.9 ± 3.0% for the retinal arterioles and 65.0 ± 5.1% for the retinal venules. The A-V difference was 31.8 ± 4.6%. The mean of the measured haemodynamic parameters was PSV 46.6 ± 9.4 cm/s, EDV 12.0 ± 3.5 cm/s, PI 1.68 ± 0.38 and RI 0.74 ± 0.05. No significant difference in oxygen saturation and haemodynamic parameters was found between the left and the right eyes or the dominant and non-dominant eye. The oximetry and ultrasound values were sex independent. The Pearson correlation coefficient demonstrated a significant yet weak negative correlation between A-V difference and RI (r = -0.321, p = 0.020). CONCLUSIONS: A negative correlation between A-V difference and resistance index was observed, suggesting that reduced oxygen consumption may reflect the increased vascular tone of the ophthalmic vessels, which is likely determined by autoregulatory mechanisms.

Very late complications of oncotherapy in glioblastoma patients: A case series.

BACKGROUND: Stroke-like syndrome is defined as a rare, delayed complication of brain oncotherapy. Cases with more favorable brain cancer diagnoses and longer life expectancy have been previously reported, but here we present, for the first time, three long-term survivors of glioblastoma with stroke-like syndromes. METHODS AND RESULTS: Three young or middle-aged patients underwent tumor resection and chemoradiotherapy. They received regular clinical and imaging follow-up with stable neurological status and no signs of tumor recurrence. They exhibited varied signs and symptoms (motor and sensory deficits, aphasia, memory and cognitive disorders, seizures, and headache) accompanied by imaging abnormalities. Stroke-like syndromes developed within 2-5 days and resolved in 2-6 weeks. Diffusion-weighted MRI and T2 brain perfusion abnormalities were demonstrated in all patients. In addition, there was focal T1 MRI contrast enhancement due to blood-brain barrier disruption. In addition to tumor recurrence, classic stroke, encephalitis, metabolic and mitochondrial disorders, and post-seizure swelling should be excluded. The imaging indicated intensive MRI scanning and symptomatic medication (steroids supplemented by antiepileptics, vasoactive agents, etc.) for judicious management. With respect to the course, an invasive procedure was still considered an option. CONCLUSION: All stroke-like syndromes are diagnoses of exclusion. To avoid misinterpretation of imaging findings as glioblastoma recurrence and avert recall oncotherapy or redundant interventions, better understanding of delayed complications of brain tumor therapy is crucial.

Changes in Brain Responses to Music and Non-music Sounds Following Creativity Training Within the "Different Hearing" Program.

The "Different Hearing" program (DHP) is an educational activity aimed at stimulating musical creativity of children and adults by group composing in the classroom, alternative to the mainstream model of music education in Czechia. Composing in the classroom in the DHP context does not use traditional musical instruments or notation, instead, the participants use their bodies, sounds originating from common objects as well as environmental sounds as the "elements" for music composition by the participants' team, with the teacher initiating and then participating and coordinating the creative process, which ends with writing down a graphical score and then performing the composition in front of an audience. The DHP methodology works with a wide definition of musical composition. We hypothesized that the DHP short-term (2 days) intense workshop would induce changes in subjective appreciation of different classes of music and sound (including typical samples of music composed in the DHP course), as well as plastic changes of the brain systems engaged in creative thinking and music perception, in their response to diverse auditory stimuli. In our study, 22 healthy university students participated in the workshop over 2 days and underwent fMRI examinations before and after the workshop, meanwhile 24 students were also scanned twice as a control group. During fMRI, each subject was listening to musical and non-musical sound samples, indicating their esthetic impression with a button press after each sample. As a result, participants' favorable feelings toward non-musical sound samples were significantly increased only in the active group. fMRI data analyzed using ANOVA with post hoc ROI analysis showed significant group-by-time interaction (opposing trends in the two groups) in the bilateral posterior cingulate cortex/precuneus, which are functional hubs of the default mode network (DMN) and in parts of the executive, motor, and auditory networks. The findings suggest that DHP training modified the behavioral and brain response to diverse sound samples, differentially changing the engagement of functional networks known to be related to creative thinking, namely, increasing DMN activation and decreasing activation of the executive network.

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.

Botulinum toxin injection changes resting state cerebellar connectivity in cervical dystonia.

In cervical dystonia, functional MRI (fMRI) evidence indicates changes in several resting state networks, which revert in part following the botulinum neurotoxin A (BoNT) therapy. Recently, the involvement of the cerebellum in dystonia has gained attention. The aim of our study was to compare connectivity between cerebellar subdivisions and the rest of the brain before and after BoNT treatment. Seventeen patients with cervical dystonia indicated for treatment with BoNT were enrolled (14 female, aged 50.2 ± 8.5 years, range 38-63 years). Clinical and fMRI examinations were carried out before and 4 weeks after BoNT injection. Clinical severity was evaluated using TWSTRS. Functional MRI data were acquired on a 1.5 T scanner during 8 min rest. Seed-based functional connectivity analysis was performed using data extracted from atlas-defined cerebellar areas in both datasets. Clinical scores demonstrated satisfactory BoNT effect. After treatment, connectivity decreased between the vermis lobule VIIIa and the left dorsal mesial frontal cortex. Positive correlations between the connectivity differences and the clinical improvement were detected for the right lobule VI, right crus II, vermis VIIIb and the right lobule IX. Our data provide evidence for modulation of cerebello-cortical connectivity resulting from successful treatment by botulinum neurotoxin.

The Central Effects of Botulinum Toxin in Dystonia and Spasticity.

In dystonic and spastic movement disorders, however different in their pathophysiological mechanisms, a similar impairment of sensorimotor control with special emphasis on afferentation is assumed. Peripheral intervention on afferent inputs evokes plastic changes within the central sensorimotor system. Intramuscular application of botulinum toxin type A (BoNT-A) is a standard evidence-based treatment for both conditions. Apart from its peripheral action on muscle spindles, a growing body of evidence suggests that BoNT-A effects could also be mediated by changes at the central level including cerebral cortex. We review recent studies employing electrophysiology and neuroimaging to investigate how intramuscular application of BoNT-A influences cortical reorganization. Based on such data, BoNT-A becomes gradually accepted as a promising tool to correct the maladaptive plastic changes within the sensorimotor cortex. In summary, electrophysiology and especially neuroimaging studies with BoNT-A further our understanding of pathophysiology underlying dystonic and spastic movement disorders and may consequently help develop novel treatment strategies based on neural plasticity.

Multiparametric Quantitative MRI in Neurological Diseases.

Magnetic resonance imaging (MRI) is the gold standard imaging technique for diagnosis and monitoring of many neurological diseases. However, the application of conventional MRI in clinical routine is mainly limited to the visual detection of macroscopic tissue pathology since mixed tissue contrasts depending on hardware and protocol parameters hamper its application for the assessment of subtle or diffuse impairment of the structural tissue integrity. Multiparametric quantitative (q)MRI determines tissue parameters quantitatively, enabling the detection of microstructural processes related to tissue remodeling in aging and neurological diseases. In contrast to measuring tissue atrophy via structural imaging, multiparametric qMRI allows for investigating biologically distinct microstructural processes, which precede changes of the tissue volume. This facilitates a more comprehensive characterization of tissue alterations by revealing early impairment of the microstructural integrity and specific disease-related patterns. So far, qMRI techniques have been employed in a wide range of neurological diseases, including in particular conditions with inflammatory, cerebrovascular and neurodegenerative pathology. Numerous studies suggest that qMRI might add valuable information, including the detection of microstructural tissue damage in areas appearing normal on conventional MRI and unveiling the microstructural correlates of clinical manifestations. This review will give an overview of current qMRI techniques, the most relevant tissue parameters and potential applications in neurological diseases, such as early (differential) diagnosis, monitoring of disease progression, and evaluating effects of therapeutic interventions.

[Aphasia associated with lacunar infarctions]. / Aphasien bei lakunären Hirninfarkten.

BACKGROUND: Typical lacunar syndromes do not include aphasia but aphasia has been reported in rare atypical lacunar syndromes. OBJECTIVE: Description of the phenomenology and of affected fiber tracts. MATERIAL AND METHODS: Case series of three patients with lacunar stroke as evidenced by magnetic resonance imaging. Identification of affected fiber tracts via fiber tracking from coregistered lesion sites in brains of two healthy participants. RESULTS: The lacunar strokes that produced aphasia were located in the very lateral territory of perforating branches of the middle cerebral artery and extended along the external capsule into its most rostrodorsal aspect. Even though the cortex, thalamus and most parts of the basal ganglia were unaffected, patients exhibited a mild to moderate nonfluent aphasia with syntactic deficits. Fiber tracking revealed that in contrast to the nonaphasic control patient with a neighboring lacunar stroke, the aphasic patient strokes involved particularly fibers of the left arcuate fascicle as well as fibers of the frontostriatal and frontal aslant tracts. CONCLUSION: Left lateral lacunar stroke can cause clinically relevant aphasia through disruption of speech-relevant fiber tracts.

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.

Modulation of the human sensorimotor system by afferent somatosensory input: evidence from experimental pressure stimulation and physiotherapy.

Peripheral afferent input is critical for human motor control and motor learning. Both skin and deep muscle mechanoreceptors can affect motor behaviour when stimulated. Whereas some modalities such as vibration have been employed for decades to alter cutaneous and proprioceptive input, both experimentally and therapeutically, the central effects of mechanical pressure stimulation have been studied less frequently. This discrepancy is especially striking when considering the limited knowledge of the neurobiological principles of frequently used physiotherapeutic techniques that utilise peripheral stimulation, such as reflex locomotion therapy. Our review of the available literature pertaining to pressure stimulation focused on transcranial magnetic stimulation (TMS) and neuroimaging studies, including both experimental studies in healthy subjects and clinical trials. Our search revealed a limited number of neuroimaging papers related to peripheral pressure stimulation and no evidence of effects on cortical excitability. In general, the majority of imaging studies agreed on the significant involvement of cortical motor areas during the processing of pressure stimulation. Recent data also point to the specific role of subcortical structures, such as putamen or brainstem reticular formation. A thorough comparison of the published results often demonstrated, however, major inconsistencies which are thought to be due to variable stimulation protocols and statistical power. In conclusion, localised peripheral sustained pressure is a potent stimulus inducing changes in cortical activation within sensory and motor areas. Despite historical evidence for modulation of motor behaviour, no direct link can be established based on available fMRI and electrophysiological data. We highlight the limited amount of research devoted to this stimulus modality, emphasise current knowledge gaps, present recent developments in the field and accentuate evidence awaiting replication or confirmation in future neuroimaging and electrophysiological studies.

Changes in oxygen saturation and the retinal nerve fibre layer in patients with optic neuritis associated with multiple sclerosis in a 6-month follow-up.

PURPOSE: Optic neuritis (ON) is an inflammatory demyelinating disorder of the optic nerve, which can be the first manifestation of multiple sclerosis (MS). The main goal was to assess changes in the retinal nerve fibre layer (RNFL) and in retinal oxygen saturation [arterial (AS), venous (VS) and arterio-venous (A-V) difference] in the affected and unaffected eye. METHODS: Fifty patients with ON due to MS within 3 months of onset of symptoms were enrolled (17 males, mean age 35.3). All patients were examined at baseline (V1) and after 6 months (V2) using optical coherence tomography (OCT) to get RNFL values; automatic retinal oximetry to obtain saturation values; and ultrasound to exclude arterial stenosis, and orbital colour Doppler imaging was performed in the ophthalmic artery. RESULTS: At V1, AS was significantly increased in affected eye compared to unaffected eye (99.5% versus 98.0%, p = 0.03). Significant decrease in A-V difference from baseline was detected in both eyes for ON eye: 32.0% versus 29.0%, p = 0.004; for fellow eye: 31.4% versus 30.0%, p = 0.04. We did not observe any changes in retinal vessel diameter. There were no changes observed in blood flow in ophthalmic artery. At V1, there were no significant differences in RNFL, and significant loss of RNFL was confirmed in the affected eye at V2 (95 µm versus 86 µm, p = 0.0002) and in comparison with the fellow eye (86 µm versus 94 µm, p = 0.0002). There were no correlations between RNFL and saturation values at V1, although at V2, there was a negative correlation between the RNFL and AS (Spearman's rho = -0.480, p = 0.003) and between the RNFL and VS (rho = -0.620, p = 0.00007). CONCLUSION: Retinal oximetry is altered in both eyes in MS patients with unilateral ON. During the course of the disease, the retinal oxygen consumption decreases to a different degree in each eye and this change is not completely followed by changes in the RNFL thickness, suggesting either sub-clinical ON or systemic effects in the clinically unaffected eye. Since this is the first and initial longitudinal evaluation of the saturation changes in MS patients, the clinical value of these findings needs to be deeper evaluated in the future studies.

Multimodal Quantitative MRI Reveals No Evidence for Tissue Pathology in Idiopathic Cervical Dystonia.

Background: While in symptomatic forms of dystonia cerebral pathology is by definition present, it is unclear so far whether disease is associated with microstructural cerebral changes in idiopathic dystonia. Previous quantitative MRI (qMRI) studies assessing cerebral tissue composition in idiopathic dystonia revealed conflicting results. Objective: Using multimodal qMRI, the presented study aimed to investigate alterations in different cerebral microstructural compartments associated with idiopathic cervical dystonia in vivo. Methods: Mapping of T1, T2, T 2 * , and proton density (PD) was performed in 17 patients with idiopathic cervical dystonia and 29 matched healthy control subjects. Statistical comparisons of the parametric maps between groups were conducted for various regions of interest (ROI), including major basal ganglia nuclei, the thalamus, white matter, and the cerebellum, and voxel-wise for the whole brain. Results: Neither whole brain voxel-wise statistics nor ROI-based analyses revealed significant group differences for any qMRI parameter under investigation. Conclusions: The negative findings of this qMRI study argue against the presence of overt microstructural tissue change in patients with idiopathic cervical dystonia. The results seem to support a common view that idiopathic cervical dystonia might primarily resemble a functional network disease.

Differential Effects of Sustained Manual Pressure Stimulation According to Site of Action.

Sustained pressure stimulation of the body surface has been used in several physiotherapeutic techniques, such as reflex locomotion therapy. Clinical observations of global motor responses and subsequent motor behavioral changes after stimulation in certain sites suggest modulation of central sensorimotor control, however, the neuroanatomical correlates remain undescribed. We hypothesized that different body sites would specifically influence the sensorimotor system during the stimulation. We tested the hypothesis using functional magnetic resonance imaging (fMRI) in thirty healthy volunteers (mean age 24.2) scanned twice during intermittent manual pressure stimulation, once at the right lateral heel according to reflex locomotion therapy, and once at the right lateral ankle (control site). A flexible modeling approach with finite impulse response basis functions was employed since non-canonical hemodynamic response was expected. Subsequently, a clustering algorithm was used to separate areas with differential timecourses. Stimulation at both sites induced responses throughout the sensorimotor system that could be mostly separated into two anti-correlated subsystems with transient positive or negative signal change and rapid adaptation, although in heel stimulation, insulo-opercular cortices and pons showed sustained activation. In direct voxel-wise comparison, heel stimulation was associated with significantly higher activation levels in the contralateral primary motor cortex and decreased activation in the posterior parietal cortex. Thus, we demonstrate that the manual pressure stimulation affects multiple brain structures involved in motor control and the choice of stimulation site impacts the shape and amplitude of the blood oxygenation level-dependent response. We further discuss the relationship between the affected structures and behavioral changes after reflex locomotion therapy.

Low-Frequency Oscillations Code Speech during Verbal Working Memory.

The way the human brain represents speech in memory is still unknown. An obvious characteristic of speech is its evolvement over time. During speech processing, neural oscillations are modulated by the temporal properties of the acoustic speech signal, but also acquired knowledge on the temporal structure of language influences speech perception-related brain activity. This suggests that speech could be represented in the temporal domain, a form of representation that the brain also uses to encode autobiographic memories. Empirical evidence for such a memory code is lacking. We investigated the nature of speech memory representations using direct cortical recordings in the left perisylvian cortex during delayed sentence reproduction in female and male patients undergoing awake tumor surgery. Our results reveal that the brain endogenously represents speech in the temporal domain. Temporal pattern similarity analyses revealed that the phase of frontotemporal low-frequency oscillations, primarily in the beta range, represents sentence identity in working memory. The positive relationship between beta power during working memory and task performance suggests that working memory representations benefit from increased phase separation.SIGNIFICANCE STATEMENT Memory is an endogenous source of information based on experience. While neural oscillations encode autobiographic memories in the temporal domain, little is known on their contribution to memory representations of human speech. Our electrocortical recordings in participants who maintain sentences in memory identify the phase of left frontotemporal beta oscillations as the most prominent information carrier of sentence identity. These observations provide evidence for a theoretical model on speech memory representations and explain why interfering with beta oscillations in the left inferior frontal cortex diminishes verbal working memory capacity. The lack of sentence identity coding at the syllabic rate suggests that sentences are represented in memory in a more abstract form compared with speech coding during speech perception and production.

Botulinum Toxin Modulates Posterior Parietal Cortex Activation in Post-stroke Spasticity of the Upper Limb.

Post-stroke spasticity (PSS) is effectively treated with intramuscular botulinum toxin type A (BoNT-A), although the clinical improvement is likely mediated by changes at the central nervous system level. Using functional magnetic resonance imaging (fMRI) of the brain, this study aims to confirm and locate BoNT-A-related changes during motor imagery with the impaired hand in severe PSS. Temporary alterations in primary and secondary sensorimotor representation of the impaired upper limb were expected. Thirty chronic stroke patients with upper limb PSS undergoing comprehensive treatment including physiotherapy and indicated for BoNT treatment were investigated. A change in PSS of the upper limb was assessed with the modified Ashworth scale (MAS). fMRI and clinical assessments were performed before (W0) and 4 weeks (W4) and 11 weeks (W11) after BoNT-A application. fMRI data were acquired using 1.5-Tesla scanners during imagery of finger-thumb opposition sequences with the impaired hand. At the group level, we separately modeled (1) average activation at each time point with the MAS score and age at W0 as covariates; and (2) within-subject effect of BoNT-A and the effect of time since W0 as independent variables. Comprehensive treatment of PSS with BoNT-A significantly decreased PSS of the upper limb with a maximal effect at W4. Task-related fMRI prior to treatment (W0) showed extensive activation of bilateral frontoparietal sensorimotor cortical areas, bilateral cerebellum, and contralesional basal ganglia and thalamus. After BoNT-A application (W4), the activation extent decreased globally, mostly in the bilateral parietal cortices and cerebellum, but returned close to baseline at W11. The intra-subject contrast revealed a significant BoNT-A effect, manifesting as a transient decrease in the activation of the ipsilesional intraparietal sulcus and superior parietal lobule. We demonstrate that BoNT-A treatment of PSS of the upper limb is associated with transient changes in the ipsilesional posterior parietal cortex, possibly resulting from temporarily altered sensorimotor upper limb representations.

Changes in sensorimotor network activation after botulinum toxin type A injections in patients with cervical dystonia: a functional MRI study.

Botulinum toxin type A (BoNT) is considered an effective therapeutic option in cervical dystonia (CD). The pathophysiology of CD and other focal dystonias has not yet been fully explained. Results from neurophysiological and imaging studies suggest a significant involvement of the basal ganglia and thalamus, and functional abnormalities in premotor and primary sensorimotor cortical areas are considered a crucial factor in the development of focal dystonias. Twelve BoNT-naïve patients with CD were examined with functional MRI during a skilled hand motor task; the examination was repeated 4 weeks after the first BoNT injection to the dystonic neck muscles. Twelve age- and gender-matched healthy controls were examined using the same functional MRI paradigm without BoNT injection. In BoNT-naïve patients with CD, BoNT treatment was associated with a significant increase of activation in finger movement-induced fMRI activation of several brain areas, especially in the bilateral primary and secondary somatosensory cortex, bilateral superior and inferior parietal lobule, bilateral SMA and premotor cortex, predominantly contralateral primary motor cortex, bilateral anterior cingulate cortex, ipsilateral thalamus, insula, putamen, and in the central part of cerebellum, close to the vermis. The results of the study support observations that the BoNT effect may have a correlate in the central nervous system level, and this effect may not be limited to cortical and subcortical representations of the treated muscles. The results show that abnormalities in sensorimotor activation extend beyond circuits controlling the affected body parts in CD even the first BoNT injection is associated with changes in sensorimotor activation. The differences in activation between patients with CD after treatment and healthy controls at baseline were no longer present.

The effects of sustained manual pressure stimulation according to Vojta Therapy on heart rate variability.

BACKGROUND: The physiotherapeutic technique of Vojta reflex locomotion is often accompanied by various autonomic activity changes and unpleasant sensations. It is unknown whether these effects are specific to Vojta Therapy. Therefore, the aim of this study was to compare changes in cardiac autonomic control after Vojta reflex locomotion stimulation and after an appropriate sham stimulation. METHODS: A total of 28 young healthy adults (20.4 - 25.7 years) were enrolled in this single-blind randomized cross-over study. Participants underwent two modes of 20-minute sustained manual pressure stimulation on the surface of the foot on two separate visits. One mode used manual pressure on the lateral heel, i.e., in a zone employed in the Vojta Therapy (active stimulation). The other mode used pressure on the lateral ankle (control), in an area not included among the active zones used by Vojta Therapy and whose activation does not evoke manifestations of reflex locomotion. Autonomic nervous system activity was evaluated using spectral analysis of heart rate variability before and after the intervention. RESULTS: The active stimulation was perceived as more unpleasant than the control stimulation. Heart rate variability parameters demonstrated almost identical autonomic responses after both stimulation types, showing either modest increase in parasympathetic activity, or increased heart rate variability with similar contribution of parasympathetic and sympathetic activity. CONCLUSION: The results demonstrate changes of cardiac autonomic control in both active and control stimulation, without evidence for a significant difference between the two.