BMC Neurology

Individuals with cerebral palsy have smaller muscle volumes normalised to body mass than their typically developing peers. The aim of this study is to investigate the relationship between lower limb muscle volume and body mass in young people with bilateral cerebral palsy and their typically developing peers. Twenty-five participants with bilateral cerebral palsy (aged 14.7±3.0 years, GMFCS level I-III) and 25 of their typically developing peers (aged 16.8±3.3 years) took part in this study. None of the participants had undergone orthopaedic surgery, botulinum toxin injections, or serial casting in the previous year. All participants underwent magnetic resonance imaging of both lower limbs. Nine major muscles of each lower limb were individually manually segmented and the muscle volumes calculated. Body mass and total lower limb muscle volume were significantly linearly related in both the cerebral palsy (R2 = 0.75, p<0.001) and typically developing (R2 = 0.77, p<0.001) groups. The slope of the relationship between muscle volume and body mass was significantly shallower in the cerebral palsy group compared to the typically developing group (p=0.007). This cross-sectional study suggests that the increase in size of lower limb muscles relative to body mass is reduced in adolescents and young adults with cerebral palsy. Longitudinal studies are required to further investigate altered muscle growth trajectories in this group and their impact on long-term mobility.

Conversion disorder (CD) is a psychiatric disorder, yet the diagnosis cannot be established without the expertise of a neurologist, as distinguishing a functional from an organic symptom relies on careful bedside examination. Joseph Babinski considered the absence of pronator drift as a ‘positive sign’ for hysterical paresis but the validity of this sign has never been evaluated. The aim of this study was to examine the sensitivity and specificity of the “drift without pronation” sign. Twenty-six patients with unilateral functional upper limb paresis diagnosed with CD (DSM-IV) and a control group of 28 patients with an organic neurological condition were consecutively included. The arm stabilisation test was performed with arms stretched out in full supination, fingers adducted, eyes closed for 10 seconds. A positive “drift without pronation” sign was defined by the presence of a downward drift without pronation. All CD subjects (100%) displayed a positive sign when only 7.1% of organic subjects did (Fisher’s p < 0.001). The sign yielded a sensitivity of 100% (95% CI:84%-100%) and a specificity of 93% (95% CI:76%-98%). The observation of a “drift without pronation” sign is specific for Conversion Disorder and can be of help in making a quick distinction between organic and functional paresis at the bedside.

Exercise has various health benefits for people with Parkinson’s disease (PD). However, implementing exercise into daily life and long-term adherence remain challenging. To increase a sustainable engagement with physical activity of people with PD, interventions that are motivating, accessible, and scalable are needed. We primarily aim to investigate whether a smartphone app (STEPWISE app) can increase physical activity (i.e., step count) in people with PD over one year. Our second aim is to investigate the potential effects of the intervention on physical fitness, and motor- and non-motor function. Our third aim is to explore whether there is a dose-response relationship between volume of physical activity and our secondary endpoints. STEPWISE is a double-blind, randomized controlled trial. We aim to include 452 Dutch people with PD who can walk independently (Hoehn & Yahr stages 1–3) and who do not take more than 7,000 steps per day prior to inclusion. Physical activity levels are measured as step counts on the participant’s own smartphone and scaled as percentage of each participant’s baseline. Participants are randomly assigned to an active control group with an increase of 5–20% (active controls) or any of the three intervention arms with increases of 25–100% (intermediate dose), 50–200% (large dose), or 100–400% (very large dose). The primary endpoint is change in step count as measured by the STEPWISE smartphone app from baseline to 52 weeks. For our primary aim, we will evaluate the between-group difference in average daily step count change from baseline to 52 weeks. For our second aim, measures of physical fitness, and motor- and non-motor function are included. For our third aim, we will associate 52-week changes in step count with 52-week changes in secondary outcomes. This trial evaluates the potential of a smartphone-based intervention to increase activity levels in people with PD. We envision that motivational apps will increase adherence to physical activity recommendations and could permit conduct of remote clinical trials of exercise for people with PD or those at risk of PD. ClinicalTrials.gov; NCT04848077; 19/04/2021. Clinicaltrials.gov/ct2/show/NCT04848077.

Strokes have recently become a leading cause of disability among Thai people. Non-invasive brain stimulation (NIBS) seems to give promising results in stroke recovery when combined with standard rehabilitation programs. To evaluate the combined effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) and cathodal transcranial direct current stimulation (tDCS) over the non-lesional primary motor cortex on upper limb motor recovery in patients with subacute stroke. No reports of a combination of these two techniques of NIBS were found in the relevant literature. This pilot study was a double-blinded, randomized controlled trial of ten patients with subacute stroke admitted to the Rehabilitation Medicine Inpatient Unit, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University. They were randomized into two groups: five in an active and five in a sham intervention group. Fugl-Meyer’s upper extremity motor score (FMA-UE) and Wolf Motor Function Test (WMFT) were used to assess motor recovery at baseline, immediately, and 1 week after stimulation. A two-way repeated ANOVA (mixed design) showed a significant improvement in FMA-UE scores in the active intervention group both immediately and 1 week after stimulation in comparison to the baseline, [time, F (2, 16) = 27.44, p < 0.001, time x group interaction, F (2, 16) = 13.29, p < 0.001]. Despite no statistical significance, a trend toward higher WMFT scores was shown in the active intervention group. A single session of low-frequency rTMS and cathodal tDCS over the non-lesional primary motor cortex may enhance upper limb motor recovery in patients with subacute stroke.

X-linked Charcot-Marie Tooth (CMT) is caused by mutations in the connexin32 gene that encodes a polypeptide which is arranged in hexameric array and form gap junctions. We describe two novel mutations in the connexin32 gene in two Norwegian families. Family 1 had a c.225delG (R75fsX83) which causes a frameshift and premature stop codon at position 247. This probably results in a shorter non-functional protein structure. Affected individuals had an early age at onset usually in the first decade. The symptoms were more severe in men than women. All had severe muscle weakness in the legs. Several abortions were observed in this family. Family 2 had a c.536 G>A (C179Y) transition which causes a change of the highly conserved cysteine residue, i.e. disruption of at least one of three disulfide bridges. The mean age at onset was in the first decade. Muscle wasting was severe and correlated with muscle weakness in legs. The men and one woman also had symptom from their hands. The neuropathy is demyelinating and the nerve conduction velocities were in the intermediate range (25–49 m/s). Affected individuals had symmetrical clinical findings, while the neurophysiology revealed minor asymmetrical findings in nerve conduction velocity in 6 of 10 affected individuals. The two novel mutations in the connexin32 gene are more severe than the majority of previously described mutations possibly due to the severe structural change of the gap junction they encode.

Patients with hereditary transthyretin amyloidosis (ATTRv) frequently experience symptoms of polyneuropathy (PN) that worsen over time and impair daily functioning. Previous analyses supported efficacy of inotersen, an antisense oligonucleotide, to slow neuropathic progression in patients with ATTRv-PN, as indicated by larger mean changes, relative to placebo, in total score and several subscales of the Neuropathy Impairment Score (NIS), and for the subset of NIS items specific to lower limbs (NIS-LL) for the overall study sample. A key objective of the current study was to evaluate efficacy of inotersen for slowing neuropathic progression in NIS/NIS-LL within key clinical subgroups of patients with ATTRv-PN. Additionally, for this study, responder definition (RD) thresholds were estimated for NIS/NIS-LL total and subscale scores, for the purpose of evaluating clinically meaningful benefit of inotersen at the individual patient-level. Post hoc analyses used data from the NEURO-TTR phase 3 trial of inotersen in patients with ATTRv-PN (NCT01737398). Treatment differences in mean changes on NIS/NIS-LL total and subscale scores from baseline to week 65 were examined within patient subgroups defined by clinical characteristics. Anchor- and distribution-based approaches estimated RDs for NIS/NIS-LL scores, with responders defined as patients who did not experience clinically meaningful neuropathic progression. Responder analyses compared the proportion of patients classified as responders for each NIS/NIS-LL score between treatment arms. Within each patient subgroup, mean increases in NIS/NIS-LL total and muscle weakness subscales were significantly smaller after 65 weeks of treatment with inotersen compared to placebo. Similar patterns were observed for some, but not all, subgroups on NIS/NIS-LL reflex subscale scores. Recommended RDs were 8.1 points for NIS total and 4.7 points for NIS-LL total. Patients receiving inotersen for 65 weeks were significantly less likely than those receiving placebo to exhibit clinically meaningful increases on NIS/NIS-LL total, muscle weakness, and sensation subscales. This study supports previous evidence for efficacy of inotersen in this patient population and provides interpretation guidelines for clinically meaningful changes in NIS/NIS-LL scores.