Continued benefit of nusinersen initiated in the presymptomatic stage of spinal muscular atrophy: 5-year update of the NURTURE study.

INTRODUCTION/AIMS: NURTURE (NCT02386553) is an open-label study of nusinersen in children (two SMN2 copies, n = 15; three SMN2 copies, n = 10) who initiated treatment in the presymptomatic stage of spinal muscular atrophy (SMA). A prior analysis after ~3 y showed benefits on survival, respiratory outcomes, motor milestone achievement, and a favorable safety profile. An additional 2 y of follow-up (data cut: February 15, 2021) are reported. METHODS: The primary endpoint is time to death or respiratory intervention (≥6 h/day continuously for ≥7 days or tracheostomy). Secondary outcomes include overall survival, motor function, and safety. RESULTS: Median age of children was 4.9 (3.8-5.5) y at last visit. No children have discontinued the study or treatment. All were alive. No additional children utilized respiratory intervention (defined per primary endpoint) since the prior data cut. Children with three SMN2 copies achieved all World Health Organization (WHO) motor milestones, with all but one milestone in one child within normal developmental timeframes. All 15 children with two SMN2 copies achieved sitting without support, 14/15 walking with assistance, and 13/15 walking alone. Mean Hammersmith Functional Motor Scale Expanded total scores showed continued improvement. Subgroups with two SMN2 copies, minimum baseline compound muscle action potential amplitude ≥2 mV, and no baseline areflexia had better motor and nonmotor outcomes versus all children with two SMN2 copies. DISCUSSION: These results demonstrate the value of early treatment, durability of treatment effect, and favorable safety profile after ~5 y of nusinersen treatment. Inclusion/exclusion criteria and baseline characteristics should be considered when interpreting presymptomatic SMA trial data.

An eight-camera fall detection system using human fall pattern recognition via machine learning by a low-cost android box.

Falls are a leading cause of unintentional injuries and can result in devastating disabilities and fatalities when left undetected and not treated in time. Current detection methods have one or more of the following problems: frequent battery replacements, wearer discomfort, high costs, complicated setup, furniture occlusion, and intensive computation. In fact, all non-wearable methods fail to detect falls beyond ten meters. Here, we design a house-wide fall detection system capable of detecting stumbling, slipping, fainting, and various other types of falls at 60 m and beyond, including through transparent glasses, screens, and rain. By analyzing the fall pattern using machine learning and crafted rules via a local, low-cost single-board computer, true falls can be differentiated from daily activities and monitored through conventionally available surveillance systems. Either a multi-camera setup in one room or single cameras installed at high altitudes can avoid occlusion. This system's flexibility enables a wide-coverage set-up, ensuring safety in senior homes, rehab centers, and nursing facilities. It can also be configured into high-precision and high-recall application to capture every single fall in high-risk zones.

Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study.

Spinal muscular atrophy (SMA) is a neurodegenerative disease associated with severe muscle atrophy and weakness in the limbs and trunk. We report interim efficacy and safety outcomes as of March 29, 2019 in 25 children with genetically diagnosed SMA who first received nusinersen in infancy while presymptomatic in the ongoing Phase 2, multisite, open-label, single-arm NURTURE trial. Fifteen children have two SMN2 copies and 10 have three SMN2 copies. At last visit, children were median (range) 34.8 [25.7-45.4] months of age and past the expected age of symptom onset for SMA Types I or II; all were alive and none required tracheostomy or permanent ventilation. Four (16%) participants with two SMN2 copies utilized respiratory support for ≥6 h/day for ≥7 consecutive days that was initiated during acute, reversible illnesses. All 25 participants achieved the ability to sit without support, 23/25 (92%) achieved walking with assistance, and 22/25 (88%) achieved walking independently. Eight infants had adverse events considered possibly related to nusinersen by the study investigators. These results, representing a median 2.9 years of follow up, emphasize the importance of proactive treatment with nusinersen immediately after establishing the genetic diagnosis of SMA in presymptomatic infants and emerging newborn screening efforts.

Effectiveness of multimodality treatment for autoimmune limbic epilepsy.

We evaluated the outcome of multimodality treatment in autoimmune limbic epilepsy in 3 consecutive patients (2 male and 1 female; age 33-55 years) presenting with a combination of focal non-convulsive status epilepticus, memory impairment, and psychosis. MRI showed right or bitemporal T2 or FLAIR hyperintensity. Video-EEG showed seizures of right temporo-occipital or bitemporal independent onset. Extensive workup failed to reveal infectious aetiology or an underlying tumour. However, the autoantibody panel was positive for one or more of these antibodies: anti-VGKC, anti-GABAB, anti-VGCC (P/Q, N types), and anti-GAD65. All patients received: (1) conventional antiepileptic drugs including levetiracetam, lacosamide, phenobarbital, lamotrigine, and valproate; (2) immunomodulatory therapy including methylprednisolone, plasmapheresis, and intravenous immunoglobulin; and (3) rituximab. After a 4-6-week in-hospital course, the seizures resolved in all patients but 2 had persistent memory impairment. None had treatment-related complications. At the time of last follow-up, 2-3 months later, 2 patients remained seizure-free while 2 had residual memory impairment. Our findings suggest that multimodality treatment with a combination of conventional AEDs, immunomodulatory therapy, and rituximab is effective and safe in autoimmune limbic epilepsy.

A rare adult cause of dizziness.

A 55-year-old man was seen with progressively worsening dizziness over 10 months. The initial assessment with unremarkable laboratory and imaging studies suggested a peripheral vestibular disorder. He was then lost to follow-up but later was seen with worsening ataxia. Additional imaging studies showed subtle parenchymal lesions in the posterior fossa. The differential diagnoses included nutritional deficiencies, autoimmune disorders, systemic malignancies, and intracranial tumors. The final diagnosis was confirmed by a biopsy.