Leonardo Lapenta

Developmental milestones in type I spinal muscular atrophy

Highlights • This paper reports patterns of natural progression in type I SMA.• The HINE is used to capture motor developmental milestones in SMA.• Motor developmental milestones are rarely acquired in type I SMA infants.

Rivastigmine for Refractory REM Behavior Disorder in Mild Cognitive Impairment.

BACKGROUND Mild Cognitive Impairment (MCI) and REM Behavior Disorder (RBD) are both associated with a degeneration of ponto-medullary cholinergic pathways. METHODS We conducted a placebo-controlled, cross-over pilot trial of Rivastigmine (RVT) in 25 consecutive patients with MCI, who presented RBD refractory to conventional first-line treatments (melatonin up to 5 mg/day and clonazepam up to 2 mg/day). RESULTS RVT treatment was followed by a significant reduction of RBD episodes when compared with placebo. CONCLUSIONS Our data suggest that, in MCI patients with RBD resistant to conventional therapies (muscle relaxants benzodiazepines or melatonin,) treatment with RVT may induce a reduction in the frequency of RBD episodes compared to placebo.

Content validity and clinical meaningfulness of the HFMSE in spinal muscular atrophy

BackgroundReports on the clinical meaningfulness of outcome measures in spinal muscular atrophy (SMA) are rare. In this two-part study, our aim was to explore patients’ and caregivers’ views on the clinical relevance of the Hammersmith Functional Motor Scale Expanded- (HFMSE).MethodsFirst, we used focus groups including SMA patients and caregivers to explore their views on the clinical relevance of the individual activities included in the HFMSE. Then we asked caregivers to comment on the clinical relevance of possible changes of HFMSE scores over time. As functional data of individual patients were available, some of the questions were tailored according to their functional level on the HFMSE.ResultsPart 1: Sixty-three individuals participated in the focus groups. This included 30 caregivers, 25 patients and 8 professionals who facilitated the discussion.The caregivers provided a comparison to activities of daily living for each of the HFMSE items.Part 2: One hundred and forty-nine caregivers agreed to complete the questionnaire: in response to a general question, 72% of the caregivers would consider taking part in a clinical trial if the treatment was expected to slow down deterioration, 88% if it would stop deterioration and 97% if the treatment was expected to produce an improvement.Caregivers were informed of the first three items that their child could not achieve on the HFMSE. In response 75% indicated a willingness to take part in a clinical trial if they could achieve at least one of these abilities, 89% if they could achieve two, and 100% if they could achieve more than 2.ConclusionsOur findings support the use of the HFMSE as a key outcome measure in SMA clinical trials because the individual items and the detected changes have clear content validity and clinical meaningfulness for patients and their caregivers.

Sleep disorders in spinal muscular atrophy

OBJECTIVE To estimate the frequency of sleep disorders in young persons with type 2 and type 3 spinal muscular atrophy (SMA), and to evaluate the relationship between sleep disorders and different variables such as motor impairment, age, use of ventilation, and use of night orthoses. METHODS A total of 85 young persons (6-25 years of age) with type 2 and type 3 SMA were assessed using the Sleep Disturbance Scale for Children (SDSC), a scale assessing different sleep factors, and the Hammersmith Functional Motor Scale Expanded (HFMSE), a scale evaluating motor impairment. RESULTS An abnormal total sleep score was found in 16.4% of children with SMA; an additional 16.7% had an abnormal score on at least one of the sleep factors assessed by the SDSC. No specific correlation was observed between sleep disturbances and functional level as expressed by the SDSC and total HFMSE scores, but the relationship with individual items on the scale was different. The SDSC total score was significantly associated with the ability to half roll on both sides and to roll from prone to supine on the HMFSE. CONCLUSION Our results demonstrate that sleep disorders are common in children with SMA.

Super-Refractory Status Epilepticus Report of a Case and Review of the Literature

Super-refractory status epilepticus (SE; ie, SE continuing or recurring despite 24 hours of general anesthesia) is a severe condition with high percentage of mortality and morbidity. Usually, this condition occurs because of serious brain damage; nevertheless, some patients develop super-refractory SE without identifiable etiology. Although not uncommonly encountered in neurointensive care, scientific data on this condition are still lacking in terms of treatment and prognosis. Herein, we report a case of super-refractory SE with recovery after 50 days, despite electroencephalographic (EEG) and magnetic resonance imaging (MRI) signs traditionally related to poor prognosis. A review of the literature on super-refractory SE is also presented.

Transient epileptic amnesia: clinical report of a cohort of patients

Transient epileptic amnesia is a seizure disorder, usually with onset in the middle-elderly and good response to low dosages of antiepileptic drugs. We describe the clinical, electroencephalography (EEG), and neuroimaging features of 11 patients with a temporal lobe epilepsy characterized by amnesic seizures as the sole or the main symptom. We outline the relevance of a detailed clinical history to recognize amnesic seizures and to avoid the more frequent misdiagnoses. Moreover, the response to monotherapy was usually good, although the epileptic disorder was symptomatic of acquired lesions in the majority of patients.

Longitudinal assessments in discordant twins with SMA

We report longitudinal clinical and neurophysiological assessments in twins affected by spinal muscular atrophy (SMA) with discordant phenotypes. The boy had the homozygous deletion of SMN1, a typical type 1 SMA course, and died at the age of eight months. His twin sister, asymptomatic at the time of the diagnosis in her brother, had the same genetic defect but she developed clinical and electrophysiological signs of type 2 SMA. The reduction of tendon reflexes was the first clinical sign at the age of 4 months, followed within few weeks, by a mild decrement in the amplitude of the compound motor action potentials. After the age of 9 months, she showed a sudden clinical and electrophysiological deterioration. Among molecular tests, we determined SMN2 copy number, SMN2 and Plastin 3 transcript levels in peripheral blood, and observed no relevant differences between twins.

6MWT can identify type 3 SMA patients with neuromuscular junction dysfunction

The aim of the study was to establish if the decrease in gait velocity on the 6 minute walk test relates to signs of neuromuscular junction dysfunction in spinal muscular atrophy type 3 patients. 6 minute walk test and low-rate repetitive nerve stimulation test were performed in fifteen ambulant patients with spinal muscular atrophy type 3 of age between 9 and 66 years. The 6 minute walk distance ranged between 66 and 575 m. The difference between the first and the 6th minute ranged between 0 and -69%. The low-rate repetitive nerve stimulation test measured in % of loss ranged between -31.7% to +4.2% to the axillary nerve. The correlation between 6 minute walk test changes and low-rate repetitive nerve stimulation test changes was 0.86. Our data suggest that the 6 minute walk test can identify fatigue in the ambulant type 3 patients who have a concurrent neuromuscular junction dysfunction. The identification of fatigue with a simple clinical test may help to target patients who may benefit from drugs that facilitate neuromuscular transmission.

Hyperventilation in patients with focal epilepsy: electromagnetic tomography, functional connectivity and graph theory. A possible tool in epilepsy diagnosis?

Purpose: Hyperventilation (HV) is a commonly used electroencephalogram activation method. Methods: We analyzed EEG recordings in 22 normal subjects and 22 patients with focal epilepsy of unknown cause. We selected segments before (PRE), during (HYPER), and 5 minutes after (POST) HV. To analyze the neural generators of EEG signal, we used standard low-resolution electromagnetic tomography (sLORETA software). We then computed EEG lagged coherence, an index of functional connectivity, between 19 regions of interest. A weighted graph was built for each band in every subject, and characteristic path length (L) and clustering coefficient (C) have been computed. Statistical comparisons were performed by means of analysis of variance (Group X Condition X Band) for mean lagged coherence, L and C. Results: Hyperventilation significantly increases EEG neural generators (P < 0.001); the effect is particularly evident in cingulate cortex. Functional connectivity was increased by HV in delta, theta, alpha, and beta bands in the Epileptic group (P < 0.01) and only in theta band in Control group. Intergroup analysis of mean lagged coherence, C and L, showed significant differences for Group (P < 0.001), Condition (P < 0.001), and Band (P < 0.001). Analysis of variance for L also showed significant interactions: Group X Condition (P = 0.003) and Group X Band (P < 0.001). Conclusions: In our relatively small group of epileptic patients, HV is associated with activation of cingulate cortex; moreover, it modifies brain connectivity. The significant differences in mean lagged coherence, path length, and clustering coefficient permit to hypothesize that this activation method leads to different brain connectivity patterns in patients with epilepsy when compared with normal subjects. If confirmed by other studies involving larger populations, this analysis could become a diagnostic tool in epilepsy.

EPA-0267 – Polysomnographic findings in a cohort of chronic insomnia patients with benzodiazepines abuse

Study objectives to evaluate sleep modifications induced by chronic benzodiazepines (BDZs) abuse. Methods cohort study, comparison of sleep measures between BDZs abusers and controls. Drug Addiction Unit (Institute of Psychiatry) and Unit of Sleep Disorder (Institute of Neurology) of the Catholic University in Rome. Six outpatients were enrolled, (4 men and 2 women, mean age 53.3±14.8, range: 34 - 70 years) affected by BDZ chronic abuse; 55 healthy controls (23 men and 32 women, mean age 54.2 ±13.0, range: 27–76 years). All patients underwent clinical evaluation, psychometric measures, ambulatory polysomnography, scoring of sleep macrostructure and microstructure (power spectral fast-frequency EEG arousal, Cyclic Alternating Pattern - CAP), Heart Rate Variability. Results BDZs abusers had relevant modification of sleep macrostructure and a marked reduction of fast-frequency EEG arousal in NREM (Patients: 6.6±3.7 events/hour, Controls 13.7±4.9 events/hour, U-test: 294, p=0.002) and REM (Patients: 8.4±2.4 events/hour, Controls 13.3±5.1 events/hour, U-test: 264, p=0.016), and of CAP rate (Patients: 15.0±8.6%, Controls: 51.2±12.1%, U-test: 325, p Discussion BDZs abusers have reduction of arousals associated with increased number of nocturnal awakenings and severe impairment of sleep architecture. The effect of chronic BDZs abuse on sleep may be described as a severe impairment of arousal dynamics; the result is the inability to modulate levels of vigilance.