Neurocognition in Congenital Central Hypoventilation Syndrome: influence of genotype and ventilation method.

BACKGROUND: Congenital Central Hypoventilation Syndrome (CCHS) is characterized by central hypoventilation due to abnormal autonomic control of breathing and global dysautonomia. Patients harbour heterozygous PHOX-2B gene mutations which are polyalanine repeats of various lengths in most of the cases. A few previous studies have reported learning difficulties and neuropsychological disorders in patients with CCHS. The aims of the present study were (1) to explore the intellectual abilities of a group of children with CCHS followed up in the centre of reference for CCHS in France using the Wechsler batteries of tests, (2) and to assess whether there was any association between CCHS characteristics and various domains of the intellectual functioning. RESULTS: There were 34 consecutive patients (15 males, 19 females) of mean (SD) age of 7.8 (3.8) years, ranging from 4 to 16 years and 6 months. Mean score of full-scale intelligence quotient was 82 (20), being in the low average range. Indexes of working memory and processing speed were significantly lower as compared to the other Wechsler indexes. There were two important findings: (1) full-scale intelligence quotient as well as indexes of verbal comprehension and processing speed were significantly greater in patients with mask ventilation than in those with tracheostomy ventilation (p = 0.012, 0.032 and 0.042 respectively); (2) most interestingly, in the patients with polyalanine repeats mutations, all intellectual indexes negatively correlated with the number of polyalanine expansion, with statistical significance reached for indexes of fluid reasoning and working memory (R = - 0.449, p = 0.032 and R = - 0.562, p = 0.012 respectively). CONCLUSIONS: CCHS increased the risk to develop neurocognitive deficiencies, affecting particularly speed of processing and working memory. Our results suggested that both genetics and ventilation method could be also involved in the physiopathology of neurocognitive impairment. Further investigations were required to untangle the complex underlying processes. Neurocognitive assessments should be performed regularly in children with CCHS in order to plan re-education programs, adapt school integration and improve quality of life.

Early Onset of Sleep-Disordered Breathing in Two Children With SEPN1-Related Myopathies.

ABSTRACT: Selenoprotein-related myopathy (SEPN1-RM) is a rare disease with a variable clinical presentation. The selenoprotein N1 gene (SEPN1) mutation causing this congenital muscular dystrophy was identified in 2001. Sleep-disordered breathing (SDB) may occur in young patients with SEPN1-RM who are still able to walk. We report the cases of two children with SEPN1-RM who presented with SDB at the ages of 7 and 12 years and for whom long-term nocturnal noninvasive ventilation yielded significant improvement. Based on literature review and our current cases, it seems that there is no obvious relationship between the time since SDB onset and outcome of pulmonary function tests or limb muscle weakness. We therefore suggest that SDB should be systematically screened for in patients with SEPN1-RM, at regular intervals using nocturnal polysomnography.

Snoring and Obstructive Sleep Apnea: Objective Efficacy and Impact of a Chairside Fabricated Mandibular Advancement Device.

PURPOSE: Obstructive sleep apnea (OSA) has been described as a common sleep respiratory disorder. Its prevalence in the adult population has been reported to be high, varying from 3% to 28%. Dental practitioners play a key role in the treatment of this disease, using tailor-made mandibular advancement devices (MADs). This pilot study assessed the efficacy and compliance of a custom-fitted thermoplastic MAD for the treatment of moderate to severe OSA syndrome. MATERIALS AND METHODS: In this open study without a control group, OSA syndrome sufferers were enrolled by four centers. One specific MAD was custom fitted to the patients. Polysomnography, Epworth, and snoring scales were administered from inclusion to 45 days postinclusion. RESULTS: The study population consisted of 33 men and 8 women; 35 patients completed the study. Patient response was high with 69% of them considered as responders, and 60% showing a complete response. Also, 77.3% of patients with moderate OSA syndrome presented a complete response. An improvement was observed in the apnea hypopnea index, which decreased from 34.1 ± 18.9 to 12.8 ± 14.1. The Epworth Sleepiness Scale score, snoring, and quality of sleep scores decreased with the device (p < 0.0001). Compliance rates were high, with patients wearing the device 6.5 nights a week. Side effects and patient complaints were minor and transient. CONCLUSION: This custom-fitted MAD improved respiratory and somnolence parameters, with response rates similar to those published in the literature with other devices.

Sleep architecture impairment in epileptic children and putative role of anti epileptic drugs.

The comorbidity between epilepsy and sleep disorders is well documented. However, the mechanisms underlining this comorbidity are not fully understood. The putative role of anti epileptic drugs in sleep architecture disturbances in epileptic children needs to be explored. In this study, we analysed sleep architecture of 75 epileptic children (30 females and 45 males), aged from 4 to 15 years (mean-age: 8.3 years). They were divided in three groups according to their antiepileptic treatments: NT group: no antiepileptic treatment (n = 20), MT group: monotherapy (n = 29) and PT group: polytherapy (n = 26). All underwent video-polysomnographic recordings to assess main sleep parameters: stages of light sleep and slow waves sleep, REM sleep, total sleep time and awakenings. Percentages of paroxystic activity duration (PA) on TST were also calculated and classified in three subgroups: (<5%, 5% ≤ PA ≤ 20% and >20%). As result, significant decreases of REM sleep and of the sleep efficiency as well as significant increased awakenings were observed in PT group comparing to the NT group. No significative difference was found concerning the light sleep and slow waves sleep. A correlation was also observed between awakenings and PA. First, our data confirm that sleep disorders remain a hidden companion of childhood epilepsy. Second, we demonstrate that anti epileptic drugs may have some causal contribution. Diagnosing sleep disturbances should be part of the management of childhood epilepsy and should be taken into account in the choice of therapeutic strategy.

Sleep-disordered breathing in children with congenital muscular dystrophies.

OBJECTIVE: Most types of neuromuscular diseases are known to be associated with a high risk of sleep-disordered breathing. We performed a prospective study in a well individualized group of muscular disorders, congenital muscular dystrophies (CMD), to characterize the frequency of sleep-disordered breathing and thereby to determine the potential usefulness of sleep studies in such patients. METHODS: Twenty CMD children (12 F, 8 M, aged 4-17 years) were included. Using overnight polysomnography, we determined the following parameters: sleep stages, sleep latency, sleep efficiency index, wake time duration, total sleep time (TST), apnea/hypopnea index (AHI), arterial blood oxygen saturation, and nocturnal paroxysmal EEG activity. RESULTS: As compared to healthy controls, we detected in our study group frequent awakenings, a decreased TST (mean 448 ± 44.4 min) and a decreased REM duration (mean 11.5 ± 3.5% of TST). Significant increase in wake time duration (28-90 min) and decrease in REM duration were observed in 12 patients. An apnea/hypopnea syndrome was detected in 13 patients (65%) with central apneas in 8, obstructive apneas in 2 and 3 mixed apneas in 3 patients. AHI was >10 in 3 cases, <10> 5 in 4 cases and were concomitant with blood oxygen de-saturation in four cases. NPA were detected in 10 patients ranging from 10 to 40% of TST. INTERPRETATION: Our results confirm the high incidence of sleep disordered breathing in children with CMD, and thereby, the usefulness of overnight polysomnography recordings in such patients.

Sleep disorders in succinic semialdehyde dehydrogenase deficiency: a family report.

BACKGROUND: Succinic semialdehyde dehydrogenase deficiency (SSADH) is a rare neurometabolic disorder involving the degradation of gamma-aminobutyric acid. Clinically, SSADH deficiency causes progressive or static encephalopathy with late infantile to early childhood onset. It is known that sleep disorders are a common clinical finding in these patients. However, very few studies have investigated sleep disorders with polysomnographies. AIM OF THE STUDY: To analyze sleep disorders breathing, sleep architecture and paroxysmal EEG activity through polysomnographic recordings of two siblings suffering from SSADH deficiency METHOD: Each patient underwent laboratory diurnal and overnight video-polysomnographic recordings in a room specially dedicated to mothers and their children. RESULTS: The background EEG activity during quiet wakefulness consisted in abnormal, diffuse, low-voltage, disorganized slow theta waves. In both patients there was a general disorganisation of the sleep architecture with an increase of light sleep and a decrease of REM sleep. In patient 1, during sleep, there were 36 hypopneas, 13 central apneas and one obstructive apnea with a variable duration of 7-30s. The apnea/hypopnea index (AHI) was 7/h and oxygen saturation dropped to 80% during the respiratory events. In patient 2, the respiratory events consisted in 8 central apneas and 23 hypopneas of 6-20s; no obstructive apneas or hypopneas were observed. The oxygen saturation dropped to 90% during the apneas and the AHI was 5/h. CONCLUSION: Sleep-disordered breathing (SDB) is a common finding in patients with SSADH deficiency and polysomnography recording is a useful tool for its diagnosis.

Exploration of small fibers for testing diabetic neuropathies.

INTRODUCTION: Electrophysiological exploration of neuropathies is a standard method of investigating the dysfunction of myelinated larger fibers (Aalpha, Abeta). However, this method cannot test dysfunctions in other fibers. To evaluate the smaller (Adelta) and unmyelinated fiber (C-fibers) lesions a quantitative method has been perfected: the study of the sensory thresholds (quantitative sensory testing: QST). It allows the investigation of the sensory symptoms and is a reproducible, non-invasive and painless method. It is used above all in patients suffering from diabetic neuropathy ('Diabetes Care 9 (1987) 432'). PATIENTS AND METHODS: We used the QST testing in comparison with nerve conduction velocities in 40 Non-Insulin-Dependent Diabetes Mellitus (NIDDM or Type II) patients in their 60s (+/-10 years). Depending on the duration of their diabetes (dd), we distinguished three groups: dd < 5 years (GI) dd from 5 to 15 years (GII) and dd > 15 years (GIII). All the patients underwent a clinical neurological examination, which enabled us to establish a gravity score comparable to the NDS (Neuropathy Disability Score: 'Muscle Nerve 10 (1988) 21'). RESULTS: Nerve conduction velocities and QST were studied for each group of patients. Electrophysiological alterations were connected to the gravity clinical score and in some asymptomatic patients a higher QST heat threshold could be observed. DISCUSSION: These results indicate that QST can detect the early dysfunction of the unmyelinated fibers in this kind of neuropathy. Subclinical detection can reduce severe neurological complications and make possible an early and effective treatment.

Evoked potentials in spinal muscular atrophy.

Visual evoked potentials, brainstem evoked responses, and somatosensory evoked potentials were evaluated in 22 children with spinal muscular atrophy, types I and II. Eleven of the children had the severe form of spinal muscular atrophy (type I) and 11 children had the intermediate form (type II). The results of visual evoked potentials, brainstem evoked responses, and somatosensory evoked potentials were compared with those obtained in a control group. Statistical analysis showed abnormalities in the different sensory modalities. A significant increase in the visual evoked potential latencies was observed and was found more often in patients with spinal muscular atrophy type I. Alterations of the somatosensory thalamocortical responses were also observed, as well as a delay in the central conduction time. Although spinal muscular atrophy is usually considered to be a purely motor disorder involving neurons of the spinal anterior horn and nuclei of the lower cranial nerves, lesions of the posterior roots, spinal ganglia, ascending tracts, lateral geniculated corpus, and thalamus have been reported. Our results suggest that sensory neuron degeneration occurs more commonly in spinal muscular atrophy than previously thought and that this process probably develops more slowly than motoneuron degeneration. Such degeneration may be associated with brain atrophy.

Severe progressive form of congenital muscular dystrophy with calf pseudohypertrophy, macroglossia and respiratory insufficiency.

A novel form of congenital muscular dystrophy in four unrelated patients is proposed. Congenital hypotonia, markedly increased CK, calf pseudohypertrophy and proximal weakness were common early findings. Two cases were severely affected since infancy and never walked. The phenotypical homogeneity was not very evident until advanced stages of the disease. All the patients showed catastrophic progression of the weakness, severe restrictive respiratory insufficiency, macroglossia, peculiar extreme amyotrophy of hands and feet, and a round and 'puffy' face. All patients became tetraplegic and required mechanical ventilation. Two cases had signs of mild cardiac involvement. The only non-tracheotomised patient died of respiratory complications. No mental retardation or specific brain abnormalities were observed. All patients showed secondary deficit of laminin 2 and up-regulation of laminin 5 in muscle. Expression of -dystroglycan was severely reduced in two available muscle samples. The known loci for congenital muscular dystrophies were excluded in the only consanguineous case by linkage analysis. Clinical, immunohistochemical and genetic findings strongly suggest a distinct entity.