Explore the vast range of titles available.

Alterations in the default mode network (DMN) are associated with aging. We assessed age-dependent changes of DMN interactions and correlations with a battery of neuropsychological tests, to understand the differences of DMN directed connectivity between young and older subjects. Using a novel multivariate analysis method on resting-state functional MRI data from fifty young and thirty-one healthy older subjects, we calculated intra- and inter-DMN 4-nodes directed pathways. For the old subject group, we calculated the partial correlations of inter-DMN pathways with: psychomotor speed and working memory, executive function, language, long-term memory and visuospatial function. Pathways connecting the DMN with visual and limbic regions in older subjects engaged at BOLD low frequency and involved the dorsal posterior cingulate cortex (PCC), whereas in young subjects, they were at high frequency and involved the ventral PCC. Pathways combining the sensorimotor (SM) cortex and the DMN, were SM efferent in the young subjects and SM afferent in the older subjects. Most DMN efferent pathways correlated with reduced speed and working memory. We suggest that the reduced sensorimotor efferent and the increased need to control such activities, cause a higher dependency on external versus internal cues thus suggesting how physical activity might slow aging.

Studies in the sensorimotor system of older versus young individuals have shown alterations in functional connectivity and organization. Our objective was to explore the implications of these differences in terms of local organizations, and to identify processes that correlate with neuropsychological parameters.Using a novel multivariate analysis method on resting-state functional MRI data obtained from 50 young and 31 older healthy individuals, we identified directed 4-node functional pathways within the sensorimotor system and examined their correlations with neuropsychological assessments.In young individuals, the functional pathways were unidirectional, flowing from the primary motor and sensory cortices to higher motor and visual regions. In older individuals, the functional pathways were more complex. They originated either from the calcarine sulcus or the insula and passed through mutually coupled high-order motor areas before reaching the primary sensory and motor cortices. Additionally, the pathways in older individuals that resembled those found in young individuals exhibited a positive correlation with years of education.The flow pattern of young individuals suggests efficient and fast information transfer. In contrast, the mutual coupling of high-order motor regions in older individuals suggests an inefficient and slow transfer, a less segregated and a more integrated organization. The differences in the number of sensorimotor pathways and of their directionality suggests reduced efferent degenerated pathways and increased afferent compensated pathways. Furthermore, the positive effect of years of education may be associated with the Cognitive Reserve Hypothesis, implying that cognitive reserve could be maintained through specific information transfer pathways.

Resistance from antagonistic muscle groups might be a crucial factor reducing function in chronic hemiparesis. The resistance due to spastic co-contraction might be reduced by botulinum toxin injections. We assessed the effects of abobotulinumtoxinA injection in the upper limb muscles on muscle tone, spasticity, active movement, and function. In this randomised, placebo-controlled, double-blind study, we enrolled adults (aged 18–80 years) at least 6 months after stroke or brain trauma from 34 neurology or rehabilitation clinics in Europe and the USA. Eligible participants were randomly allocated in a 1:1:1 ratio with a computer-generated list to receive a single injection session of abobotulinumtoxinA 500 U or 1000 U or placebo into the most hypertonic muscle group among the elbow, wrist, or finger flexors (primary target muscle group [PTMG]), and into at least two additional muscle groups from the elbow, wrist, or finger flexors or shoulder extensors. Patients and investigators were masked to treatment allocation. The primary endpoint was the change in muscle tone (Modified Ashworth Scale [MAS]) in the PTMG from baseline to 4 weeks. Secondary endpoints were Physician Global Assessment (PGA) at week 4 and change from baseline to 4 weeks in the perceived function (Disability Assessment Scale [DAS]) in the principal target of treatment, selected by the patient together with physician from four functional domains (dressing, hygiene, limb position, and pain). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01313299. 243 patients were randomly allocated to placebo (n=81), abobotulinumtoxinA 500 U (n=81), or abobotulinumtoxinA 1000 U (n=81). Mean change in MAS score from baseline at week 4 in the PTMG was −0·3 (SD 0·6) in the placebo group (n=79), −1·2 (1·0) in the abobotulinumtoxinA 500 U group (n=80; difference −0·9, 95% CI −1·2 to −0·6; p<0·0001 vs placebo), and −1·4 (1·1) in the abobotulinumtoxinA 1000 U group (n=79; −1·1, −1·4 to −0·8; p<0·0001 vs placebo). Mean PGA score at week 4 was 0·6 (SD 1·0) in the placebo group (n=78), 1·4 (1·1) in the abobotulinumtoxinA 500 U group (n=80; p=0·0003 vs placebo), and 1·8 (1·1) in the abobotulinumtoxinA 1000 U group (n=78; p<0·0001 vs placebo). Mean change from baseline at week 4 in DAS score for the principal target of treatment was −0·5 (0·7) in the placebo group (n=79), −0·7 (0·8) in the abobotulinumtoxinA 500 U group (n=80; p=0·2560 vs placebo), and −0·7 (0·7) in the abobotulinumtoxinA 1000 U group (n=78; p=0·0772 vs placebo). Three serious adverse events occurred in each group and none were treatment related; two resulted in death (from pulmonary oedema in the placebo group and a pre-existing unspecified cardiovascular disorder in the abobotulinumtoxinA 500 U group). Adverse events that were thought to be treatment related occurred in two (2%), six (7%), and seven (9%) patients in the placebo, abobotulinumtoxinA 500 U, and abobotulinumtoxinA 1000 U groups, respectively. The most common treatment-related adverse event was mild muscle weakness. All adverse events were mild or moderate. AbobotulinumtoxinA at doses of 500 U or 1000 U injected into upper limb muscles provided tone reduction and clinical benefit in hemiparesis. Future research into the treatment of spastic paresis with botulinum toxin should use active movement and function as primary outcome measures. Ipsen.

Background While immediate benefits of levodopa–carbidopa intestinal gel (LCIG) are evident in patients with Parkinson’s disease (PD), long-term LCIG effects require further study. Objectives We explored long-term LCIG on motor symptoms, nonmotor symptoms (NMS), and LCIG treatment settings in patients with advanced PD (APD). Methods Data were obtained (medical records and patient visit) from COSMOS, a multinational, retrospective, cross-sectional post-marketing observational study in patients with APD. Patients were stratified into 5 groups based on LCIG treatment duration at the patient visit, from 1–2 to > 5 years LCIG. Between-group differences were assessed for changes from baseline in LCIG settings, motor symptoms, NMS, add-on medications, and safety. Results Out of 387 patients, the number of patients per LCIG group was: > 1– ≤ 2 years LCIG ( n  = 156); > 2– ≤ 3 years LCIG ( n  = 80); > 3– ≤ 4 years LCIG ( n  = 61); > 4– ≤ 5 years LCIG ( n  = 30); > 5 years LCIG ( n  = 60). Baseline values were similar; data reported are changes from the baseline. There were reductions in “off” time, dyskinesia duration, and severity across LCIG groups. Prevalence, severity, and frequency of many individual motor symptoms and some NMS were reduced amongst all LCIG groups, with few differences between groups. Doses for LCIG, LEDD and LEDD for add-on medications were similar across groups both at LCIG initiation and patient visit. Adverse events were similar across all LCIG groups and consistent with the established safety profile of LCIG. Conclusions LCIG may provide sustained, long-term symptom control, while potentially avoiding increases in add-on medication dosages. Trial registration ClinicalTrials.gov Identifier: NCT03362879. Number and date: P16-831, November 30, 2017.

Tools for post-operative localization of deep brain stimulation (DBS) electrodes may be of major benefit in the evaluation of the stimulation area. However, little is known about their precision. This study compares 3 different software packages used for DBS electrode localization. T1-weighted MRI images before and after the implantation of the electrodes into the subthalamic nucleus for DBS in 105 Parkinson’s disease patients were processed using the pipelines implemented in Lead-DBS, SureTune4, and Brainlab. Euclidean distance between active contacts determined by individual software packages and in repeated processing by the same and by a different operator was calculated. Furthermore, Dice coefficient for overlap of volume of tissue activated (VTA) was determined for Lead-DBS. Medians of Euclidean distances between estimated active contact locations in inter-software package comparison ranged between 1.5 mm and 2 mm. Euclidean distances in within-software package intra- and inter-rater assessments were 0.6–1 mm and 1–1.7 mm, respectively. Median intra- and inter-rater Dice coefficients for VTAs were 0.78 and 0.75, respectively. Since the median distances are close to the size of the target nucleus, any clinical use should be preceded by careful review of the outputs.

Gait disturbances have emerged as some of the main therapeutic concerns in late-stage Parkinson's disease (PD) treated with dopaminergic therapy and deep brain stimulation (DBS). External cues may help to overcome freezing of gait (FOG) and improve some of the gait parameters. To evaluate the effect of 3D visual cues and STN-DBS on gait in PD group. We enrolled 35 PD patients treated with DBS of nucleus subthalamicus (STN-DBS). Twenty-five patients (5 females; mean age 58.9 ±6.3) and 25 sex- and age-matched controls completed the gait examination. The gait in 10 patients deteriorated in OFF state. The severity of PD was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (HY). The PD group filled the Falls Efficacy Scale-International (FES) and Freezing of Gait Questionnaire (FOGQ). Gait was examined using the GaitRite Analysis System, placed in the middle of the 10m marked path. The PD group was tested without dopaminergic medication with and without visual cueing together with the DBS switched ON and OFF. The setting of DBS was double-blind and performed in random order. The UPDRS was 21.9 ±9.5 in DBS ON state and 41.3 ±13.7 in DBS OFF state. HY was 2.5 ±0.6, FES 12.4 ±4.1 and FOGQ 9.4 ±5.7. In the DBS OFF state, PD group walked more slowly with shorter steps, had greater step length variability and longer duration of the double support phase compared to healthy controls. The walking speed and step length increased in the DBS ON state. The double support phase was reduced with 3D visual cueing and DBS; the combination of both cueing and DBS was even more effective. Cueing with 3D visual stimuli shortens the double support phase in PD patients treated with DBS-STN. The DBS is more effective in prolonging step length and increasing gait speed. We conclude that 3D visual cueing can improve walking in patients with DBS.

Mixed movement disorder due to pathogenic variants in the gene (MxMD- ) is a rare condition characterized predominantly by paroxysmal involuntary choreiform movements involving the limbs, face, and neck, often accompanied by dystonia and myoclonus. Speech disturbances, delayed motor development, cognitive impairment, axial hypotonia, and episodic exacerbations of dyskinesia are also common features. Currently, treatment strategies remain limited; however, several studies indicate a beneficial effect of caffeine in the management of dyskinesia. This clinical report aims to present a case of MxMD- showing a high therapeutic response to caffeine. To our knowledge, this is the first reported Ukrainian patient with this condition demonstrating dramatic improvement in paroxysmal dyskinesia after treatment with high-dose caffeine. In our clinical observation, administration of caffeine at a total daily dose of 600 mg resulted in significant clinical improvement in an adult patient with MxMD over a follow-up period of at least 6 months. No adverse events or side effects were reported.

Electrode implantation into the subthalamic nucleus for deep brain stimulation in Parkinson's disease (PD) is associated with a temporary motor improvement occurring prior to neurostimulation. We studied this phenomenon by functional magnetic resonance imaging (fMRI) when considering the Unified Parkinson's Disease Rating Scale (UPDRS-III) and collateral oedema. Twelve patients with PD (age 55.9± (SD)6.8 years, PD duration 9-15 years) underwent bilateral electrode implantation into the subthalamic nucleus. The fMRI was carried out after an overnight withdrawal of levodopa (OFF condition): (i) before and (ii) within three days after surgery in absence of neurostimulation. The motor task involved visually triggered finger tapping. The OFF/UPDRS-III score dropped from 33.8±8.7 before to 23.3±4.8 after the surgery (p<0.001), correlating with the postoperative oedema score (p<0.05). During the motor task, bilateral activation of the thalamus and basal ganglia, motor cortex and insula were preoperatively higher than after surgery (p<0.001). The results became more enhanced after compensation for the oedema and UPDRS-III scores. In addition, the rigidity and axial symptoms score correlated inversely with activation of the putamen and globus pallidus (p<0.0001). One month later, the OFF/UPDRS-III score had returned to the preoperative level (35.8±7.0, p = 0.4).In conclusion, motor improvement induced by insertion of an inactive electrode into the subthalamic nucleus caused an acute microlesion which was at least partially related to the collateral oedema and associated with extensive impact on the motor network. This was postoperatively manifested as lowered movement-related activation at the cortical and subcortical levels and differed from the known effects of neurostimulation or levodopa. The motor system finally adapted to the microlesion within one month as suggested by loss of motor improvement and good efficacy of deep brain stimulation.

The effects of dopaminergic therapy for Parkinson’s disease (PD) on the brain functional architecture are still unclear. We investigated this topic in 31 PD patients (disease duration: 11.2 ± (SD) 3.6 years) who underwent clinical and MRI assessments under chronic dopaminergic treatment (duration: 8.3 ± (SD) 4.4 years) and after its withdrawal. Thirty healthy controls were also included. Functional and morphological changes were studied, respectively, with eigenvector centrality mapping and seed-based connectivity, and voxel-based morphometry. Patients off medication, compared to controls, showed increased connectivity in cortical sensorimotor areas extending to the cerebello-thalamo-cortical pathway and parietal and frontal brain structures. Dopaminergic therapy normalized this increased connectivity. Notably, patients showed decreased interconnectedness in the medicated compared to the unmedicated condition, encompassing putamen, precuneus, supplementary motor and sensorimotor areas bilaterally. Similarly, lower connectivity was found comparing medicated patients to controls, overlapping with the within-group comparison in the putamen. Seed-based analyses revealed that dopaminergic therapy reduced connectivity in motor and default mode networks. Lower connectivity in the putamen correlated with longer disease duration, medication dose, and motor symptom improvement. Notably, atrophy and connectivity changes were topographically dissociated. After chronic treatment, dopaminergic therapy decreases connectivity of key motor and default mode network structures that are abnormally elevated in PD off condition.

Background  There are gaps in our neurobiological understanding of functional movement disorder (FMD). Objectives We investigated gray matter volumetric profiles in FMD, and related findings to resting‐state functional connectivity (rsFC) profiles using Human Connectome Project data. Methods Volumetric differences between 53 FMD patients and 50 controls were examined, as well as relationships between individual differences in FMD symptom severity and volumetric profiles. Atrophy network mapping was also used to probe whether FMD‐related structural alterations preferentially impacted brain areas with dense rsFC. Results Compared to controls without neurological comorbidities (albeit with mild depression and anxiety as a group), the FMD cohort did not show any volumetric differences. Across patients with FMD, individual differences in symptom severity negatively correlated with right supramarginal and bilateral superior temporal gyri volumes. These findings remained significant adjusting for FMD subtype or antidepressant use, but did not remain statistically significant adjusting for depression and anxiety scores. Symptom severity‐related structural alterations mapped onto regions with dense rsFC—identifying several disease epicenters in default mode, ventral attention, and salience networks. Conclusions This study supports that FMD is a multinetwork disorder with an important role for the temporoparietal junction and its related connectivity in the pathophysiology of this condition. More research is needed to explore the intersection of functional neurological symptoms and mood. This study examined relationships between individual differences in FMD symptom severity and volumetric profiles. Atrophy network mapping also probed whether FMD‐related structural alterations preferentially impacted brain areas with dense rsFC. This study supports that FMD is a multi‐network disorder with an important role for the temporoparietal junction.