Spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) is a rare autosomal recessive neurodevelopmental disorder linked to biallelic variants in the SLC1A4 gene, which encodes the ASCT1 amino acid transporter critical for neutral amino acid uptake in neurons. While SLC1A4 mutations are well established in SPATCCM, the potential impact of additional genetic factors on disease progression remains unexplored. We report a rare case of an 8-month-old male with severe global developmental delay and progressive microcephaly, identified with whole-exome sequencing to have a novel combination of homozygous SLC1A4 (p.Arg457Trp) and heterozygous APOE (p.Cys130Arg) mutations. Neuroimaging revealed severe hypomyelination and diffuse white matter abnormalities. This is the first reported case of SPATCCM with an APOE variant, implicating a potential interplay between amino acid transport deficiencies and lipid metabolism in brain development.

TPK1-related thiamine metabolism dysfunction syndrome (TPK1 deficiency) is characterized by mild-to-profound developmental delay and intellectual disability with or without regression, dystonia, episodes of encephalopathy, spasticity, ataxia, seizures, and abnormal muscle tone. Most individuals have normal initial achievement of developmental milestones followed by a febrile illness precipitating episodic encephalopathy and neuroregression. Less commonly, developmental delay is observed prior to the onset of encephalopathy episodes. Early treatment with thiamine supplementation can lead to partial or near-complete alleviation of neurologic manifestations. Untreated individuals often experience significant neurologic morbidity.

Cerebral palsy (CP) is traditionally characterized as a disorder of motor impairment; however, growing evidence suggests it reflects broader dysregulation across multiple physiological systems. We present a longitudinal case study examining whether pairing transcutaneous spinal neuromodulation (TSN) with a proprioceptive-derived intervention (PDI) can engage systems-level functional adaptation in an adolescent with CP spastic diplegia, whose progress had plateaued after years of conventional therapy. Across two years of the intervention, structured clinical observations revealed progressive and reversible improvements spanning posture, locomotion, fine motor control, speech, vision, hearing, sleep, endurance, executive function, and psychosocial engagement. Motor coordination often changed rapidly with stimulation, autonomic functions evolved over intermediate timescales, and longer-lasting changes consistent with support of physiological capacity and recovery emerged more gradually. The task specificity, state dependence, and reversibility of these effects are consistent with activity-dependent processes guided by enhanced proprioceptive signaling during TSN + PDI. Importantly, these adaptations did not emerge uniformly across domains. These findings support a reconceptualization of CP not solely as an isolated motor disorder, but as a condition of maladaptive multisystem regulation that may be amenable to noninvasive, proprioceptively derived neuromodulatory rehabilitation strategies. While limited to a single case, this work highlights underappreciated neuroadaptive potential in CP and motivates future controlled studies targeting systems-level recovery.

Canavan disease is a leukodystrophy characterized by neurodevelopmental delays, macrocephaly, and tone abnormalities. The phenotypic spectrum ranges from the more severe typical Canavan disease (85%-90% of individuals) to the less severe atypical Canavan disease (10%-15%). Typical Canavan disease is characterized by neurodevelopmental impairment evident by ages three to five months, followed by neurodegeneration and developmental regression. The clinical course of atypical Canavan disease is more variable, with neurodevelopmental delay usually becoming evident in the first years of life and frequently followed by developmental regression later in childhood or adolescence. All individuals with Canavan disease have reduced life expectancy, with the majority surviving to age ten years and the minority living to adulthood.

Spasticity assessment after stroke requires objective measures of stretch reflex excitability, yet clinically practical and structurally interpretable approaches for identifying stretch reflex thresholds (SRTs) remain limited. We present an ultrasound-derived method for quantifying SRTs during controlled tendon tapping by tracking tendon-to-bone (T2B) displacement, which reflects local musculotendon deformation. Ten individuals with chronic stroke participated. A LinMot tapper delivered graded mechanical taps to the distal biceps tendon. A B-mode ultrasound probe integrated into the tapper tip tracked T2B displacement, while a force sensor and surface electromyograms (EMG) recorded reflex responses. T2B reflex amplitude was defined as the post-tap peak tendon displacement relative to its pre-tap position. As indentation depth increased, T2B reflex amplitude exhibited a nonlinear-to-linear pattern, enabling clear identification of SRT as the transition point between the two. T2B reflex amplitude showed strong within-subject correlations with reflex force and rectified integrated EMG (RIEMG) (force: mean r = 0.86; RIEMG: mean r = 0.82), comparable to the force-RIEMG correlation. T2B-based SRT estimates demonstrated within-session repeatability (CV = 10.48 ± 10.06%), comparable to force-based SRTs and lower than RIEMG-based SRTs. Baseline T2B preload distance varied across individuals and was positively associated with SRT, suggesting that a structure-informed interpretation may provide physiological context beyond externally imposed indentation depth.

BackgroundAlthough several studies have examined gait changes associated with continuous intrathecal baclofen (CITB) infusion for spasticity in ambulatory patients with acquired brain injury (ABI), none has included a control group.ObjectiveTo assess long-term changes in gait kinematics associated with CITB infusion for post-ABI spasticity.MethodsForty-three consecutive ABI patients underwent gait evaluations during an ITB bolus trial, with follow-up gait data available in 17 pump recipients (re-evaluated 24 ± 17 months after implantation, dose range 95-590 µg/day) and 8 non-recipients (re-evaluated 30 ± 19 months after screening). Temporospatial gait parameters and lower extremity joint range of motion (ROM) were analyzed.ResultsChanges in temporospatial gait parameters from baseline to follow-up did not differ significantly between pump recipients and non-recipients. Likewise, there were no significant between-group differences in changes in ROM over time except for a 7.5° increase in more-affected (MA) knee ROM during swing in pump recipients, compared with a 2.4° decrease in non-recipients (ANOVA group×time interaction, P = 0.027). Secondary analyses showed that baseline average Ashworth score in the MA leg correlated significantly with changes in MA stance time and less-affected initial double support time (r ≥ |0.56|, P ≤ 0.029) in pump recipients only.ConclusionsThe modest improvements in gait kinematics in pump recipients appeared to have limited clinical significance, considering no concurrent improvements in average gait speed and the study limitations. The overall results suggest that gait speed may be useful for goal setting, but it should not be considered the sole measure of CITB efficacy.

Vanishing white matter (VWM) disease is a leukodystrophy caused by mutations in EIF2B1-5 genes, which impair cellular stress responses and protein synthesis regulation, leading to astrocytic dysfunction and white matter degeneration. While typically a pediatric condition, adult-onset cases are increasingly recognized. We report a 39-year-old Brazilian woman with a six-year history of progressive cognitive decline, gait impairment, and rapid deterioration following an infection. Neurological examination revealed spastic tetraparesis and severe cognitive impairment. Brain magnetic resonance imaging (MRI) showed diffuse white matter abnormalities with cystic degeneration. Whole-exome sequencing identified a homozygous EIF2B3 c.260C>T (p.Ala87Val) variant, previously associated with a founder effect in Quebec but not reported in Brazil. This case highlights the phenotypic variability of VWM, stress-triggered exacerbations, and the importance of genetic testing in adult patients with cognitive decline. It also expands the genotypic diversity of VWM in Brazil and underscores the need for multidisciplinary care.