Most individuals with spinal muscular atrophy (SMA) on disease-modifying therapies continue to have chronic motor impairment. Insights into brain involvement in SMA may open new pathways for adjunctive therapies to optimize outcomes. We aimed to characterize macrostructural brain abnormalities detected by MRI in individuals with SMA compared with peer controls. We conducted a cross-sectional case-control study of children and adults with a confirmed genetic diagnosis of 5q SMA, and peer controls matched by age and sex. Brain MRIs acquired on a 3T MRI scanner through a standardized research protocol were reviewed to qualitatively assess the presence of macrostructural changes. The primary outcome was the presence of any structural brain anomaly on MRI. In addition, the total volume of each participant's lateral ventricles was quantified by volumetry using MRIcron. Genetic and clinical variables, including SMN2 copy number and motor function (Hammersmith Functional Motor Scale Expanded and Revised Upper Limb Module scores), were then correlated with neuroimaging findings. A total of 42 participants completed the study (mean age 17.4, range 7–40; 67% male). Of the 21 individuals with 5q SMA, 9 (43%) had macrostructural brain abnormalities identified on MRI compared with 2 of 21 (10%) peer controls (odds ratio 7.1, 95% confidence interval 1.4–34.0). In patients with SMA, the most common structural changes were widening of the arachnoid spaces (n = 4) and ventriculomegaly (n = 4). Individuals with SMA had larger median lateral ventricular volume than their normally developing peers (9.3 mL, interquartile range [IQR] 5.5–13.1 vs 5.3 mL, IQR 3.8–9.8; p = 0.034). Structural brain abnormalities were more frequent in those with 2 SMN2 copies (3/5, 60%) compared with 3 or 4 SMN2 copies (4/10, 40% and 2/6, 33% respectively), not reaching significance. We found no association between structural changes and motor function scores. Individuals with SMA have higher rates of macrostructural brain abnormalities than their neurotypical peers, suggesting CNS involvement in SMA. Understanding changes in the brain architecture of the SMA population can inform the development of adjunct therapies targeting the CNS and potentially guide rehabilitation strategies.

Absence seizures are classically associated with behavioral arrest and transient deficits in consciousness, yet substantial variability exists in the severity of the impairment. Despite several decades of research on the topic, the pathophysiology of absence seizures and the mechanisms underlying behavioral impairment remain unclear. Several rationales have been proposed including widespread cortical deactivation, reduced perception of external stimuli, and transient suspension of the default mode network, among others. This review aims to summarize the current knowledge on the neural correlates of impaired consciousness in absence seizures. We review evidence from studies using animal models of absence epilepsy, electroencephalography, functional magnetic resonance imaging, magnetoencephalography, positron emission tomography, and single photon emission computed tomography.

Clinical trials in spinal muscular atrophy (SMA) have shown that early treatment improves outcomes, prompting inclusion in newborn screening (NBS) programs worldwide. The province of Quebec launched its SMA NBS program in October 2023, with a rapidly progressive implementation. We describe the program’s first-year experience, focusing on screening yield, birth prevalence, clinical outcomes, and challenges. In the first year, 6 of 67,933 newborns screened positive for SMA, all subsequently confirmed by diagnostic testing. Of these, 4 newborns (67%) had two SMN2 copies and 2 newborns (33%) had four copies. Additionally, one symptomatic compound heterozygote infant presented during this period, indicating a provincial birth prevalence of 1 in 9705 live births (95% CI: 1:20,032–1:4701). Two newborns with two SMN2 copies were symptomatic at initial consultation; one transitioned to palliative care and died at 43 days of life. Surviving newborns initiated treatment at a median age of 30 days (range: 9–103 days), with four receiving onasemnogene abeparvovec and one nusinersen. Motor outcomes at three or six months were stable or improved among treated infants. Overall, the Quebec SMA NBS pilot program successfully identified affected newborns, facilitated early access to therapy, and provided the first provincial estimate of SMA birth prevalence. Improved sample shipping and processing times are needed to maximize the program’s impact, which is expected with full automation.

Despite the use of disease-modifying therapies, many individuals with spinal muscular atrophy (SMA) have chronic motor impairments. Although neuromodulation therapies have been used successfully in other neurological disorders to optimize outcomes, the effects of early motor unit dysfunction on brain connectivity in SMA remain largely unknown. This study aimed to investigate differences in resting-state functional connectivity between individuals with SMA and peer controls. We conducted a multicenter cross-sectional case control study of children and adults with 5q SMA, and controls matched by age and sex. Blood oxygen level dependent (BOLD) fluctuations at rest were acquired on 3T magnetic resonance imaging (MRI) scanners. Seed-to-voxel functional connectivity analyses were performed using the connectivity toolbox (CONN), with site as a covariate. Twenty-five seeds of interest were selected a priori based on functional relevance and prior literature, using regions of interest defined by the Harvard-Oxford atlas. Connectivity between regions of interest identified on primary analysis, expressed as Fisher-transformed correlation coefficients, were then assessed for correlation with motor function, SMN2 copy number, and SMA type. Forty-two participants (21 with SMA and 21 peer controls) completed the study (mean age 17.4 years, range 7-40; 67% males). At the time of the study, 24% of individuals with SMA were independently ambulant. Compared to controls, individuals with SMA demonstrated lower functional connectivity within the cerebellum and within salience network regions, alongside higher functional connectivity between the precentral gyri and areas of the default mode network (corrected p<0.05). No association between the connectivity values and motor function, SMN2 copy number, or SMA type was observed when controlling for age at MRI and site. Differences in resting-state functional connectivity in individuals with SMA encompass various brain networks, extending beyond motor areas. Insights into the reorganization of brain networks in SMA may open new pathways for adjunctive therapies to optimize outcomes.

Post-hemorrhagic ventricular dilatation (PHVD) is a serious complication of intraventricular hemorrhage (IVH) in preterm newborns and is associated with significant impairments. The natural evolution of PHVD and developmental implications of spontaneous resolution are not well established. To investigate the natural evolution of PHVD and compare neurodevelopmental impairments in newborns with (1) spontaneous resolution of PHVD; (2) persistent PHVD and (3) PHVD who underwent neurosurgical intervention. We conducted a multicenter retrospective cohort study of 5238 newborns born at ≤34 weeks’ gestational age (GA) admitted to two tertiary Neonatal Intensive Care Units (NICU) between 2012 and 2020. Head ultrasounds (HUS) of 476 newborns with IVH grade ≥2 were reviewed to identify PHVD, defined as ventricular index (VI) >97^th centile (p97) for GA and anterior horn width (AHW) >6mm on any HUS in the first 6 weeks of life. Newborns with PHVD were divided into three groups, Group 1: newborns with spontaneous resolution of PHVD, defined as the regression of both lateral ventricles below the VI and AHW thresholds, Group 2: newborns with persistent PHVD absent neurosurgical intervention and Group 3: newborns who underwent any neurosurgical intervention. Neurodevelopmental outcomes at 18 months corrected, obtained through chart review, were compared. Of 108 newborns with PHVD, 88 survived to NICU discharge (mean GA 28.4 weeks, SD 2.8; median age at PHVD diagnosis 8.0 days, IQR 5.0-12.8). Overall, 34/88 (38.6%) newborns had spontaneous resolution of PHVD (Group 1). The median time between PHVD diagnosis and spontaneous resolution was 14.0 days (IQR 6.8-32.3) (Figure). In Group 3, the median time between PHVD diagnosis and the first neurosurgical intervention was 14.0 days (IQR 7.0-23.0). Group 1 had significantly smaller maximal VI (1.8, 3.4, and 11.1mm above p97, p<0.001) and AHW (7.2, 10.8, and 20.3mm, p<0.001) than Groups 2 and 3, respectively, and were less likely to have bilateral PHVD (OR 0.47, 95% CI 0.33-0.67) than Group 3. Neurodevelopmental outcome data at 18 month were available for 53/88 (60.2%) survivors (Table). Group 1 had lower rates of cerebral palsy (17.4% vs 45.8%; p=0.037), global developmental delay (17.4% vs 50.0%; p=0.018), epilepsy (4.3% vs 29.2%; p=0.048) and involvement of ≥3 allied health professionals (34.8% vs 70.8%; p=0.013) compared to Group 3. Newborns with PHVD without spontaneous resolution are at higher risk for significant neurodevelopmental impairments despite neurosurgical interventions, which may be due to more prominent ventricular dilatation. Strategies aimed at mitigating the burden of impairments in patients without spontaneous resolution are needed.

Transient global amnesia (TGA) is a benign clinical syndrome characterized by the sudden onset of anterograde amnesia with preserved consciousness and no focal neurologic deficits, resolving within...