A new score combining compound muscle action potential (CMAP) amplitudes and motor score is predictive of motor outcome after AVXS-101 (Onasemnogene Abeparvovec) SMA therapy.

Spinal muscular atrophy 1 (SMA1) is a severe early genetic disease with degeneration of motor neurons. Motor development is still suboptimal after gene replacement therapy in symptomatic patients. In this study, compound muscle action potential (CMAP) amplitudes were explored as predictors of motor recovery after gene therapy. Thirteen symptomatic SMA1 patients were prospectively included at the Necker Enfants Malades Hospital, Paris, France (Cohort 1) and 12 at the other pediatric neuromuscular reference centers of the French Filnemus network (Cohort 2). In Cohort 1, median CMAP amplitudes showed the best improvement between baseline and the 12 months visit compared to the other tested nerves (ulnar, fibular and tibial). High median CMAP amplitudes at baseline was associated with unaided sitting achievement at M6 (AUC 90%). None of the patients with CHOPINTEND at M0 < 30/64 and median CMAP < 0.5 mV achieved unaided sitting at M6 and this result was confirmed on Cohort 2 used as an independent validation data. Thus, median CMAP amplitude is a valid biomarker for routine practice to predict sitting at M6. A median CMAP amplitude over 0.5 mV at baseline may predict better motor recovery.

[Pharyngeal-cervical-brachial syndrome: A rare form of Guillain-Barré syndrome with severe acute bulbar palsy]. / Le syndrome pharyngo-cervico-brachial: un tableau de syndrome de Guillain-Barré atypique avec paralysie bulbaire sévère.

The pharyngeal-cervical-brachial (PCB) variant of Guillain-Barré syndrome is rare in children. It is characterized by oropharyngeal, neck, and upper limb muscle involvement, without ataxia and disturbed consciousness. Although associated with anti-GT1a antibodies, there is no single clinical or serological marker of PCB syndrome. We report on two cases in a 14-year-old and a 15-year-old females. The first symptom was acute dysphonia followed by severe bulbar palsy with deglutition disorders, associated with involvement of other cranial nerves and arm and leg weakness. One of the girls had normal deep tendon reflexes. Both had normal cerebral imaging and normal cerebrospinal fluid. No sign of neuropathy was found on nerve conduction studies. The diagnosis of PCB syndrome was established based on the presence of antiganglioside antibodies. Both adolescents had IgG anti-GT1a antibodies. Anti-GQ1b and anti-GT1b antibodies were associated in the first case, anti-GM1 and anti-GD1a in the second case. Clinical improvement was fast after treatment with intravenous immunoglobulin therapy. Recovery was complete. Only a few cases of children and adolescents with PCB syndrome have been reported. The main differential diagnoses were excluded with brain MRI. The neurophysiological findings in PCB syndrome are axonal neuropathy rather than demyelinating neuropathy, which might be normal in the early stages of the disease. Positivity of anti-GT1a IgG antibodies is very helpful for the diagnosis of PCB syndrome. In atypical cases of bulbar palsy with other cranial nerve involvement and normal brain MRI, diagnosis of PCB syndrome should be considered. Recognizing the atypical cases of Guillain-Barré syndrome enables anticipatory monitoring for disease complications and identifies therapeutic options. The short- and long-term outcome of the PCB syndrome after intravenous immunoglobulin treatment seems favorable.

Optimal parameters of transcranial electrical stimulation for intraoperative monitoring of motor evoked potentials of the tibialis anterior muscle during pediatric scoliosis surgery.

OBJECTIVE: Transcranial electric stimulation elicited muscle motor evoked potentials (TESmMEPs) is one of the best methods for corticospinal tract's function monitoring during spine and spinal cord surgeries. A train of multipulse electric stimulation is required for eliciting TESmMEPs under general anaesthesia. Here, we investigated the best stimulation parameters for eliciting and recording tibialis anterior's TESmMEPs during paediatric scoliosis surgery. PATIENTS AND METHODS: Numbers of pulses (NOP), inter-stimulus intervals (ISI) and current intensities allowing the best size tibialis anterior muscle's TESmMEPs under general anaesthesia, were tested and collected during 77 paediatric scoliosis surgery monitoring procedures in our hospital. Individual pulse duration was kept at 0.5 ms and stimulating electrodes were positioned at C1 and C2 (International 10-20-EEG-System) during all the tests. RESULTS: The NOP used for eliciting the best tibialis anterior TESmMEPs response was 5, 6, and 7 respectively in 21 (27%), 47 (61%) and 9 (12%) out of the 77 patients. The ISI was 2, 3 and 4 ms respectively in 13 (17%), 55 (71%) and 9 (12%) of them. The current intensity used varied from 300 to 700 V (mean: 448±136 V). CONCLUSION: Most patients had 6 as best NOP (61%) and 3 ms as best ISI (71%). These findings support that a NOP of 6 and an ISI of 3 ms should be preferentially used as optimal stimulation settings for intraoperative tibialis anterior muscle's TESmMEPs eliciting and recording during paediatric scoliosis surgery.

Intraoperative neurophysiologic monitoring in spine surgery. Developments and state of the art in France in 2011.

Intraoperative spinal cord monitoring consists in a subcontinuous evaluation of spinal cord sensory-motor functions and allows the reduction the incidence of neurological complications resulting from spinal surgery. A combination of techniques is used: somatosensory evoked potentials (SSEP), motor evoked potentials (MEP), neurogenic motor evoked potentials (NMEP), D waves, and pedicular screw testing. In absence of intraoperative neurophysiological testing, the intraoperative wake-up test is a true form of monitoring even if its latency long and its precision variable. A 2011 survey of 117 French spinal surgeons showed that only 36% had neurophysiological monitoring available (public healthcare facilities, 42%; private facilities, 27%). Monitoring can be performed by a neurophysiologist in the operating room, remotely using a network, or directly by the surgeon. Intraoperative alerts allow real-time diagnosis of impending neurological injury. Use of spinal electrodes, moved along the medullary canal, can determine the lesion level (NMEP, D waves). The response to a monitoring alert should take into account the phase of the surgical intervention and does not systematically lead to interruption of the intervention. Multimodal intraoperative monitoring, in presence of a neurophysiologist, in collaboration with the anesthesiologist, is the most reliable technique available. However, no monitoring technique can predict a delayed-onset paraplegia that appears after the end of surgery. In cases of preexisting neurological deficit, monitoring contributes little. Monitoring of the L1-L4 spinal roots also shows low reliability. Therefore, monitoring has no indication in discal and degenerative surgery of the spinal surgery. However, testing pedicular screws can be useful. All in all, thoracic and thoracolumbar vertebral deviations, with normal preoperative neurological examination are currently the essential indication for spinal cord monitoring. Its absence in this indication is a lost opportunity for the patient. If neurophysiological means are not available, intraoperative wake-up test is a minimal obligation.

Severe neonatal episodic laryngospasm due to de novo SCN4A mutations: a new treatable disorder.

BACKGROUND: Myotonia is unusual in infants, and not well-known. METHODS: We describe neonatal life-threatening features of myotonia caused by de novo mutations in the muscle sodium channel gene SCN4A. RESULTS: Three male neonates initially displayed episodic laryngospasms, with face and limb myotonia appearing later. We found SCN4A de novo mutations in these neonates: p.Gly1306Glu in 2 unrelated cases and a novel mutation p.Ala799Ser in the third. Two patients survived their respiratory attacks and were efficiently treated by sodium channel blockers (mexiletine, carbamazepine) following diagnosis of myotonia. CONCLUSION: Severe neonatal episodic laryngospasm is a new phenotype caused by a sodium channelopathy, which can be alleviated by channel blockers.

[Ketogenic regime as anti-epileptic treatment: its use in 29 epileptic children]. / Le régime cétogène à visée anti-épileptique: son utilisation chez 29 enfants épileptiques.

INTRODUCTION: The ketogenic diet is a treatment option for patient with intractable or refractory epilepsy. It is a high-fat, low protein, low carbohydrate diet developed in 1920s. Recent research publications and media interest have renewed debate on the merits of ketogenic diet. POPULATION: We report our experience with 29 children suffering from refractory epilepsy, treated with the ketogenic diet. No surgical option was available. Modalities are explained. RESULTS: The ketogenic diet improved seizure control in 12/29 cases. It appeared effective in infants with infantile spasms. Refractory-status epilepticus responded to the ketogenic diet (3/6 cases). Migrating partial seizures in infancy were always refractory to the diet. Compliance with the diet was good. Adverse effects must be compared with the toxicity of antiepileptic drugs. One child had hypokaliemia with cardiac complication. CONCLUSION: The ketogenic diet should be continued during one or 2 years when it is effective. It should be considered as an alternative therapy for children with refractory epilepsy.