Vagus nerve stimulation for treatment of drug-resistant epilepsy: a systematic review and meta-analysis.

To analyze the efficacy and safety of high-frequency VNS versus control (low-frequency VNS or no VNS) in patients with DRE using data from randomized controlled trials (RCTs). An electronic literature search was conducted on PubMed, EMBASE, and Cochrane Controlled Register of Trials (CENTRAL); 12 RCTs reporting seizure frequency or treatment response in studies containing a high-frequency VNS treatment arm (conventional VNS or transcutaneous VNS [tVNS]) compared to control (low-frequency VNS or no VNS) were included. Seizure frequency, treatment response (number of patients with ≥ 50% reduction in seizure frequency), quality of life (QOL), and adverse effects were analyzed. Seizure frequency was reported in 9 studies (718 patients). Meta-analysis with random-effects models favored high-frequency VNS over control (standardized mean difference = 0.82, 95%-CI = 0.39-1.24, p < .001). This remained significant for subgroup analyses of low-frequency VNS as the control, VNS modality, and after removing studies with moderate-to-high risk of bias. Treatment response was reported in 8 studies (758 patients). Random-effects models favored high-frequency VNS over control (risk ratio = 1.57, 95%-CI = 1.19-2.07, p < .001). QOL outcomes were reported descriptively in 4 studies (363 patients), and adverse events were reported in 11 studies (875 patients). Major side effects and death were not observed to be more common in high-frequency VNS compared to control. High-frequency VNS results in reduced seizure frequency and improved treatment response compared to control (low-frequency VNS or no VNS) in patients with drug-resistant epilepsy. Greater consideration for VNS in patients with DRE may be warranted to decrease seizure frequency in the management of these patients.

Long-term Follow-up of Pulmonary Function and Scoliosis in Patients With Duchenne's Muscular Dystrophy and Spinal Muscular Atrophy.

BACKGROUND: Spine surgery for neuromuscular scoliosis in patients with Duchenne's Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA) remained controversial. This study aimed to review the long-term results of spine surgery and its effect on pulmonary function in these patients. METHODS: A retrospective review was conducted for the above patients who had undergone surgery from 1990 to 2006 in a tertiary hospital. Their yearly lung function tests, clinical records, and x-ray films before and after surgery were reviewed. All patients had at least 2 lung function tests performed before surgery and at least 3 lung function tests performed after surgery. Records of perioperative pulmonary infections that resulted in hospital admissions were also retrieved from the hospital computer system. RESULTS: Forty patients were reviewed: 29 with DMD, 11 with SMA. The mean follow-up period was 11.6 years. For patients with DMD, the mean correction of Cobb's angle from surgery was 34.1 degrees. The rate of decline of the predicted forced vital capacity preoperatively was 7.80% per year, and was reduced to 4.26% per year postoperatively (P<0.001). For patients with SMA, the mean correction of Cobb's angle from surgery was 44.1 degrees. The rate of decline of the predicted forced vital capacity preoperatively was 5.31% per year, and was reduced to 1.77% per year postoperatively (P<0.001). For both DMD and SMA patients, the difference between the rate of preoperative and postoperative pulmonary infections that resulted in hospital admission were, however, not significant (P=0.433 and 0.452, respectively). CONCLUSIONS: Scoliosis surgery in patients with DMD and SMA results in a long-term decreased rate of decline in pulmonary function over a follow-up period of more than 10 years. The level of the apical vertebrae of the scoliosis did not demonstrate a significant trend on the pulmonary function. The frequency of chest infections did not improve by scoliosis surgery. LEVEL OF SIGNIFICANCE: Level III­Retrospective study.

Causes, functional outcomes and healthcare utilisation of people with cerebral palsy in Singapore.

INTRODUCTION: A voluntary cerebral palsy (CP) registry was established in 2017 to describe the clinical characteristics and functional outcomes of CP in Singapore. METHODS: People with CP born after 1994 were recruited through KK Women's and Children's Hospital, National University Hospital and Cerebral Palsy Alliance Singapore. Patient-reported basic demographics, service utilisation and quality of life measures were collected with standardised questionnaires. Clinical information was obtained through hospital medical records. RESULTS: Between 1 September 2017 and 31 March 2020, 151 participants were recruited. A majority (n=135, 89%) acquired CP in the pre/perinatal period, where prematurity (n=102, 76%) and the need for emergency caesarean section (n=68, 50%) were leading risk factors. Sixteen (11%) of the total participants had post-neonatally acquired CP. For predominant CP motor types, 109 (72%) had a spastic motor type; 32% with spastic mono/hemiplegia, 41% diplegia, 6% triplegia and 21% quadriplegia. The remaining (42, 27.8%) had dyskinetic CP. Sixty-eight (45.0%) participants suffered significant functional impairment (Gross Motor Functional Classification System levels IV-V). Most participants (n=102, 67.5%) required frequent medical follow-up (≥4 times a year). CONCLUSION: Optimisation of pre- and perinatal care to prevent and manage prematurity could reduce the burden of CP and their overall healthcare utilisation.

Perspectives on Palliative Care Among Duchenne Muscular Dystrophy Patients and Their Families in Singapore.

INTRODUCTION: With better medical care, patients with Duchenne muscular dystrophy (DMD) now live longer but face more complex medical and social needs. This study described the perceptions of DMD patients and their families of disease-specific palliative care services in Singapore. MATERIALS AND METHODS: A multicentre, cross-sectional study involving DMD patients and their families was carried out. Structured questionnaires were administered to them to collect data on their understanding of palliative care, health services accessed and desired by them and quality of life. RESULTS: A total of 30 pairs of DMD patients and their caregivers responded. Most patients were >13 years old (70%) and non-ambulant (86%). Most of them and their families (70%) were also not aware of palliative care and support services that were available to them in Singapore. Additionally, they perceived greater financial assistance and better transport services as resources that could better meet their care needs. The presence of scoliosis and need for ventilatory support were associated with lower quality of life in patients. CONCLUSION: There is a need to improve awareness and provision of palliative care services for DMD patients in Singapore where discussion of end-of-life care is often considered taboo. Prevention and correction of scoliosis and provision of appropriate ventilatory support may improve quality of life in DMD patients.

Influence of visual-coupling on bimanual coordination in unilateral spastic cerebral palsy.

Controlling two objects simultaneously during a bimanual task is a cognitively demanding process; both hands need to be temporally and spatially coordinated to achieve the shared task goal. Children with unilateral spastic cerebral palsy (USCP) exhibit severe sensory and motor impairments to one side of their body that make the process of coordinating bimanual movements particularly exhausting. Prior studies have shown that performing visually-coupled task could reduce cognitive interference associated with performing 'two tasks at once' in an uncoupled bimanual task. For children with USCP, who also present with cognitive delay, performing this type of task may allow them to process and plan their movement faster. We tested this hypothesis by examining the grip force control of 7 children with USCP during unimanual and visually-coupled bimanual tasks. Results demonstrated that despite the visual coupling, the bimanual coordination of these children remained impaired. However, there may be a potential benefit of visually-coupled task in encouraging both hands to initiate in concert. The implication of the study for children with USCP is discussed.

Urea cycle disorder presenting as bilateral mesial temporal sclerosis - an unusual cause of seizures: a case report and review of the literature.

BACKGROUND: Urea cycle disorders are secondary to defects in the system converting ammonia into urea, causing accumulation of ammonia and other byproducts which are neurotoxic. Ornithine transcarbamylase deficiency is the most common of the urea cycle disorders and frequently presents with coma or seizures during hyperammonemia. However, seizures can also occur without metabolic decompensation. CASE PRESENTATION: We describe a 23-year-old Chinese woman with urea cycle disorder who presented with confusion due to focal seizures arising from the left frontotemporal region. Interestingly, her ammonia levels remained normal during the seizures. Neuroimaging showed bilateral mesial temporal sclerosis. Her seizures were successfully controlled with two anti-epileptic medications. CONCLUSIONS: This case adds evidence of the predisposition of the temporal lobe to injury in urea cycle disorder. Urea cycle disorder can lead to mesial temporal sclerosis which leads to increased susceptibility of patients to seizures regardless of their metabolic state.

Pediatric rehabilitation with the reachMAN's modular handle.

This paper presents the results of a preliminary study with one cerebral palsy child using the ReHaptic Handle, a novel robotic device for the pediatric rehabilitation of upper limb function. The device has two degrees-of-freedom to train pinching, forearm supination/pronation and wrist flexion/extension movements. Interactive computer games have been implemented to increase subjects' participation and engagement, thus promoting motor recovery. Pinching, with the index finger and thumb, forearm supination/pronation as well as wrist flexion/extension were trained two or three times a week for 15 minutes each. An increase in forearm supination/pronation movement precision and smoothness was observed with the subject, as well as a reduction in the movement duration.

Simple instructions for partial sleep deprivation prior to pediatric EEG reduces the need for sedation.

OBJECTIVE: To study the effects of providing simple instructions for partial sleep deprivation on the necessity for sedation in children and adolescents undergoing electroencephalography (EEG). METHODS: Children and adolescents below 18 years undergoing non-urgent routine EEG were studied for the need for sedation during the EEG test. Two consecutive 3-year periods were reviewed. During the first 3 years no instructions for sleep deprivation were given, and during the second 3-year period, simple instructions were given to the patient or parents of young children to have less sleep prior to the EEG test. This was achieved by using the same sleep deprivation schedule irrespective of the age of the patient. RESULTS: In the first 3-year period between January 1996 and December 1998, 785 non-urgent routine EEG recordings were performed in which only 146 (19%) pediatric patients managed to fall asleep without the need for any sedation within 30 min of being ready for the sleep recording. When partial sleep deprivation was implemented in the 3-year period between January 2000 and December 2002, 449 (55%) out of 821 patients undergoing the test fell asleep in the laboratory without sedation, an overall increase of 36%. Analyzing the different age-specific groups, the maximal increase in the success for natural sleep following partial sleep deprivation was 44% for pediatric patients aged above 10 years. CONCLUSIONS: Simple instructions for partial sleep deprivation prior to the EEG reduced the need for sedation in children and adolescents undergoing the test.

Afebrile seizures associated with minor infections: comparison with febrile seizures and unprovoked seizures.

This study aimed to demonstrate that afebrile seizures provoked by minor infections constitute a distinct epilepsy syndrome different from febrile seizures and unprovoked afebrile seizures. Of the children who were admitted to hospitals for their first seizure, 1170 had febrile seizures, 286 had provoked seizures, and 125 had unprovoked afebrile seizures. Children with provoked seizures were afebrile at the time of seizure but manifested definite symptoms or signs of minor infection, for example, cough, coryza, vomiting or diarrhea, normal metabolic and cerebrospinal fluid investigations, and no obvious cause for their seizures. The average follow-up was 6.1 years. The Kaplan-Meier estimate of risk at 5 years for subsequent unprovoked afebrile seizures after a first febrile seizure, provoked seizure, or unprovoked afebrile seizure was 1.6%, 5.7%, and 65.7% respectively. All differences were statistically significant (P < 0.0014). In conclusion, afebrile seizures provoked by minor illnesses constitute a distinct type of situation-related seizures, which have not been previously described. Children with provoked seizures have a much lower risk of subsequent unprovoked afebrile seizures than patients with the first afebrile seizure. Careful inquiry for symptoms of minor infections when children present with their first afebrile seizure will help determine the risk for subsequent seizures and the need for antiepileptic drugs.

Microarray analysis unmasked paternal uniparental disomy of chromosome 12 in a patient with isolated sulfite oxidase deficiency.

BACKGROUND: In the investigation of a proband with a biochemical diagnosis of isolated sulfite oxidase deficiency, we identified a homozygous nonsense mutation of the SUOX gene in the proband. However, the mutation was only detected in the father and not the mother. Deletion of the SUOX gene of the mother and paternal disomy of chromosome 12, where the SUOX gene is located, were suspected in view that allele dropout of the mother non-amplified wild-type allele is unlikely. METHODS: To distinguish the two possible causes, we performed a genome wide microarray analysis in the patient and parents using high-density single-nucleotide microarrays. Whole genome allele sharing of the genomes of the patient and parents were performed by dChip. RESULTS: In the proband, the whole genome scan showed loss of heterozygosity (LOH) of the entire chromosome 12. However, the LOH is copy neutral and deletion of the SUOX gene of the mother was thus excluded. On whole genome allele sharing analysis, the proband showed a high degree of allele sharing with the father and a very low allele sharing with the mother only in chromosome 12. The cause of the homozygosity of the mutation of the patient is UPD (12) pat. CONCLUSIONS: To the best of our knowledge, this study is the first UPD (12) pat causing isolated sulfite oxidase deficiency in humans. Even with one parent being a carrier of an autosomal recessive disease, a fetus with the autosomal recessive disease is still possible. This will have clinical impact on genetic counseling.

Central nervous system side effects of first- and second-generation antihistamines in school children with perennial allergic rhinitis: a randomized, double-blind, placebo-controlled comparative study.

OBJECTIVE: Allergic rhinitis is common and on the rise. Antihistamines are the mainstay of treatment and are the most commonly prescribed drugs in Singapore. Treatment-related sedation and its effect on cognition are a major concern. First- and second-generation antihistamines show varying degrees of sedation, but to date, objective studies in children are lacking. The objective of this study was to assess the sedating effect of cetirizine (second-generation antihistamine) and chlorpheniramine (first-generation antihistamine) compared with placebo using an objective neurophysiological test. METHODS: This was a prospective, double-blind, placebo-controlled, randomized, single-dose, 3-way crossover study. Twenty-four children aged 7 to 14 years with allergic rhinitis completed the study. All children were randomly allocated to medication sequences and received 3 different drugs on 3 different days, at least 1 week apart. The P300 event-related potential was used as an objective test of sedation. Subjective assessment was by a visual analog scale. RESULTS: Chlorpheniramine and cetirizine increased P300 latency when compared with baseline. No significant increase was obtained with placebo. The significant increase in P300 latency was not accompanied by significant change in subjective somnolence as measured by the visual analog scale. CONCLUSION: We have shown that cetirizine has sedative properties in children. The lack of correlation between P300 latency and the visual analog scale indicates that sedation induced by these drugs may not be subjectively noted.