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Sustained involuntary muscle activity (IMA) is a highly disabling and not completely understood phenomenon that occurs after a central nervous system lesion. We tested the feasibility of in-field IMA measuring at an acute rehabilitation ward. We used wearable probes for single differential surface EMG (sEMG), inclusive of a 3D accelerometer, onboard memory and remote control. We collected 429 h of data from the biceps brachii of 10 patients with arm plegia. Data quality was first verified in the time and frequency domains. Next, IMA was automatically identified based on the steady presence of motor unit action potential (MUAP) trains at rest. Feasibility was excellent in terms of prep time and burden to the clinical staff. A total of 350.5 h of data (81.7%) were reliable. IMA was found in 85.9 h (25%). This was often present in the form of exceedingly long-lasting trains of one or a few MUAPs, with differences among patients and variability, both within and between days in terms of IMA duration, root mean square (RMS) and peak-to-peak amplitude. Our results proved the feasibility of using wearable probes for single differential sEMG to identify and quantify IMA in plegic muscles of bedridden acute neurological patients. Our results also suggest the need for long-lasting acquisitions to properly characterize IMA. The possibility of easily assessing IMA in acute inpatients can have a huge impact on the management of their postures, physiotherapy and treatments.

This observational study aimed at investigating pain in stroke patients with upper limb spastic dystonia. Forty-one consecutive patients were enrolled. A 0–10 numeric rating scale was used to evaluate pain at rest and during muscle tone assessment. Patients were asked to indicate the most painful joint at passive mobilization (shoulder, elbow, wrist-fingers). The DN4 questionnaire was administered to disclose neuropathic pain. All patients were assessed just before and 1 month after incobotulinumtoxin-A treatment. Pain was present in 22 patients, worsened or triggered by passive muscle stretching. DN4 scored < 4 in 20 patients. The most painful joints were wrist–fingers in 12 patients, elbow in 5 patients and shoulder in the remaining 5 patients. Both elbow and wrist–fingers pain correlated with muscle tone. BoNT-A treatment reduced pain in all the joints, including the shoulder. We discussed that nociceptive pain is present in a vast proportion of patients with upper limb spastic dystonia. BoNT-A treatment reduced both spastic dystonia and pain in all the joints but the shoulder, where the effect on pain could be mediated by the reduction of pathological postures involving the other joints.

Keywords: 3D printing, finger splints, hand function, Sollerman scale, spastic dystonia

By blocking the release of neurotransmitters, botulinum toxin A (BoNT-A) is an effective treatment for muscle over-activity and pain in stroke patients. BoNT-A has also been reported to increase passive range of motion (p-ROM), the decrease of which is mainly due to muscle shortening (i.e., muscle contracture). Although the mechanism of action of BoNT-A on p-ROM is far from understood, pain relief may be hypothesized to play a role. To test this hypothesis, a retrospective investigation of p-ROM and pain was conducted in post-stroke patients treated with BoNT-A for upper limb hypertonia. Among 70 stroke patients enrolled in the study, muscle tone (Modified Ashworth Scale), pathological postures, p-ROM, and pain during p-ROM assessment (Numeric Rating Scale, NRS) were investigated in elbow flexors (48 patients) and in finger flexors (64 patients), just before and 3–6 weeks after BoNT-A treatment. Before BoNT-A treatment, pathological postures of elbow flexion were found in all patients but one. A decreased elbow p-ROM was found in 18 patients (38%). Patients with decreased p-ROM had higher pain-NRS scores (5.08 ± 1.96, with a pain score ≥8 in 11% of cases) than patients with normal p-ROM (0.57 ± 1.36) (p < 0.001). Similarly, pathological postures of finger flexion were found in all patients but two. A decreased finger p-ROM was found in 14 patients (22%). Pain was more intense in the 14 patients with decreased p-ROM (8.43 ± 1.74, with a pain score ≥ 8 in 86% of cases) than in the 50 patients with normal p-ROM (0.98 ± 1.89) (p < 0.001). After BoNT-A treatment, muscle tone, pathological postures, and pain decreased in both elbow and finger flexors. In contrast, p-ROM increased only in finger flexors. The study discusses that pain plays a pivotal role in the increase in p-ROM observed after BoNT-A treatment.

Background Hereditary spastic paraplegia type 56 (HSP56) is a rare, autosomal recessive neurodegenerative disorder caused by pathogenic variants in the CYP2U1 gene which encodes a cytochrome P450 enzyme that is critical for fatty acid metabolism and mitochondrial function. Herein, we explore the diagnosis and management of three patients with novel variants in CYP2U1 and review the literature on phenotype-genotype correlations in CYP2U1 -related disorders. Through whole-genome sequencing and targeted validation by Sanger sequencing, we identified novel causative CYP2U1 variants in three female patients from two families who presented with early-onset spastic paraplegia. Case presentation Twin sisters of Middle Eastern descent were found to carry a novel, homozygous in-frame deletion, c.367_375del (p.Gly123_Tyr125del), that was predicted to disrupt CYP2U1 protein structure and enzymatic stability. A third patient of South Asian descent carried a homozygous missense variant in CYP2U1 , c.1355 A > T (p.Asp452Val), also not previously reported in public databases. This patient also had axonal sensory motor polyneuropathy. Clinically, all the patients presented with progressive lower-limb spasticity and delayed motor milestones. Cognitive impairment and brain magnetic resonance imaging (MRI) findings of hypomyelination were observed in both twins, but not in the third patient. Comprehensive metabolic panels for all three patients showed no evidence of folate deficiency. A literature review revealed no genotype–phenotype correlation for CYP2U1 , as both truncating and missense variants can present with clinical findings of variable severity and age of onset. Conclusions These findings document the CYP2U1 genotypic and phenotypic spectrum and reinforce the need for early recognition and metabolic monitoring for patients with HSP56. Further studies are warranted to evaluate whether interventions targeting nutrition or mitochondrial function can improve outcomes in CYP2U1 -related neurodegeneration.

Spastic paraplegia type 3A (SPG3A) is the second most common form of hereditary spastic paraplegia (HSP). This autosomal-dominant-inherited motor disorder is caused by heterozygous variants in the ATL1 gene which usually presents as a pure childhood-onset spastic paraplegia. Affected individuals present muscle weakness and spasticity in the lower limbs, with symptom onset in the first decade of life. Individuals with SPG3A typically present a slow progression and remain ambulatory throughout their life. Here we report three unrelated individuals presenting with very-early-onset (before 7 months) complex, and severe HSP phenotypes (axial hypotonia, spastic quadriplegia, dystonia, seizures and intellectual disability). For 2 of the 3 patients, these phenotypes led to the initial diagnosis of cerebral palsy (CP). These individuals carried novel ATL1 pathogenic variants (a de novo ATL1 missense p.(Lys406Glu), a homozygous frameshift p.(Arg403Glufs*3) and a homozygous missense variant (p.Tyr367His)). The parents carrying the heterozygous frameshift and missense variants were asymptomatic. Through these observations, we increase the knowledge on genotype–phenotype correlations in SPG3A and offer additional proof for possible autosomal recessive forms of SPG3A, while raising awareness on these exceptional phenotypes. Their ability to mimic CP also implies that genetic testing should be considered for patients with atypical forms of CP, given the implications for genetic counseling.

Siddiqi syndrome is a rare autosomal recessive deafness-dystonia disorder caused by pathogenic variants in the FITM2 gene. To date, only 5 unrelated families have been reported in the literature carrying loss-of-function variants in FIMT2 gene. In this report, we describe a 29-year-old woman with compound heterozygous novel variants identified by trio-based exome sequencing. She carries the paternally inherited delins variant c.158_161delinsTCAT, p.(Arg53_Asn54delinsLeuIle) and the maternally inherited frameshift variant c.567del, p.(Thr190ProfsTer9) in FITM2 gene. The patient exhibits the main features of the disease, including deafness, intellectual disability, regression of motor skills and poor overall growth. Additionally, she presents with spastic paraplegia which supports recent phenotypic expansion. We describe for the first time, novel brain magnetic resonance imaging signal alterations, not previously associated with this disorder. These neuroimaging findings may provide new insights into the neurological manifestations of Siddiqi syndrome. This case expands the phenotypic and molecular spectrum of FITM2 associated disease and emphasizes the adult-features of this syndrome. Graphical abstract

ObjectivesMaximum phonation time is a simple test used to assess glottic competency. Our objective was to evaluate any correlation between maximum phonation time and spasmodic dysphonia as adductor spasmodic dysphonia and abductor spasmodic dysphonia have an adductor and abductor overdrive, respectively.MethodsA 3-year data-review was performed for patients diagnosed with adductor spasmodic dysphonia, abductor spasmodic dysphonia and mixed spasmodic dysphonia. Maximum phonation time was noted on the first visit and compared with a control group.ResultsAverage maximum phonation time in adductor spasmodic dysphonia, abductor spasmodic dysphonia and control group was 25 seconds, 9 seconds and 16 seconds. A significant difference was found for adductor spasmodic dysphonia and abductor spasmodic dysphonia. A receiver operating characteristic curve analysis between adductor spasmodic dysphonia and control groups showed a positive predictive value of 81.3 per cent, negative predictive value of 83.9 per cent, sensitivity of 79.6 per cent and specificity of 85.2 per cent. Level of evidence = 4.ConclusionWe recommend that maximum phonation time be added to the diagnostic armamentarium of spasmodic dysphonia. This correlation between maximum phonation time and spasmodic dysphonia has not been previously published.

Background Hereditary spastic paraplegia (HSP) is a rare genetic disorder associated with mutations in > 80 loci designated SPG (SPastic parapleGia). The phenotypic spectrum of HSP can extend to include other neurologic features, including movement disorders. Our aim was to investigate genotype–phenotype associations in HSP with a focus on movement disorders.MethodsWe performed a systematic review and individual participant data (IPD)-level meta-analysis by retrieving publications from Medline/EMBASE/Web of Science on HSP with a SPG genotype. Studies were included only if individual-level information was accessible and at least one patient with a movement disorder was reported for that genotype. Out of 21,957 hits, 192 manuscripts with a total of 1413 HSP cases were eligible. Data were compared between two HSP groups: manifested with (HSP-MD, n = 767) or without (HSP-nMD, n = 646) a movement disorder.ResultsThe HSP-MD group had an older age of onset (20.5 ± 16.0 vs. 17.1 ± 14.2 yr, p < 0.001) and less frequent autosomal dominant inheritance (7.6% vs. 30.1%, p < 0.001) compared to HSP-nMD. SPG7 (31.2%) and SPG11 (23.8%) were the most frequent genotypes in the HSP-MD group. HSP-MD with SPG7 had higher frequency of later onset during adulthood (82.9% vs. 8.5%), ataxia (OR = 12.6), extraocular movement disturbances (OR = 3.4) and seizure (OR = 3.7) compared to HSP-MD with SPG11. Conversely, SPG11 mutations were more frequently associated with consanguinity (OR = 4.1), parkinsonism (OR = 7.8), dystonia (OR = 5.4), peripheral neuropathy (OR = 26.9), and cognitive dysfunction (OR = 34.5).ConclusionThis systematic IPD-level meta-analysis provides the largest data on genotype–phenotype associations in HSP-MD. Several clinically relevant phenotypic differences were found between various genotypes, which can possibly facilitate diagnosis in resource-limited settings.

Hereditary Spastic Paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders primarily characterized by progressive lower limb spasticity and weakness. Among them, Spastic Paraplegia Type 56 (SPG56) is a rare autosomal recessive form caused by CYP2U1 mutations. While spasticity is the hallmark of SPG56, recent reports have shown expanding phenotypic variability, including dystonia. We report an 8-month-old Arab male who presented with generalized tonic seizures and abnormal head movements, later identified as dystonic in nature. MRI revealed cerebral atrophy and delayed myelination. Given the early symptom onset and unexplained neurodevelopmental presentation, exome-based next-generation sequencing was performed. This identified a homozygous missense variant in CYP2U1 (c.947 A > T; p.Asp316Val), classified as likely pathogenic. This variant has previously been associated with SPG56 but rarely with dystonia as a predominant feature. Over 6 months of follow-up, seizure frequency decreased markedly and dystonia improved substantially on sodium valproate and levetiracetam, although mild dystonic movements persisted and no lower-limb spasticity was observed. This case highlights the diagnostic value of exome-based genetic testing in unexplained early-onset neurodevelopmental disorders. It also underscores the phenotypic heterogeneity of SPG56 and suggests that dystonia may, in some cases, be an early and dominant manifestation of CYP2U1-related pathology. Reporting such rare presentations is essential to broaden our understanding of the clinical spectrum of CYP2U1 mutations.