Adverse Events and Complications Associated With Vagal Nerve Stimulation: An Analysis of the Manufacturer And User Facility Device Experience Database.

OBJECTIVE: Drug-resistant epilepsy (DRE) can have devastating consequences for patients and families. Vagal nerve stimulation (VNS) is used as a surgical adjunct for treating DRE not amenable to surgical resection. Although VNS is generally safe, it has its inherent complications. With the increasing number of implantations, adequate patient education with discussion of possible complications forms a critical aspect of informed consent and patient counseling. There is a lack of large-scale reviews of device malfunction, patient complaints, and surgically related complications available to date. MATERIALS AND METHODS: Complications associated with VNS implants performed between 2011 and 2021 were identified through a search of the United States Food and Drug Administration Manufacturer And User Facility Device Experience (MAUDE) data base. We found three models on the data base, CYBERONICS, INC pulse gen Demipulse 103, AspireSR 106, and SenTiva 1000. The reports were classified into three main groups, "Device malfunction," "Patient complaints," and "Surgically managed complications." RESULTS: A total of 5888 complications were reported over the ten-year period, of which 501 reports were inconclusive, 610 were unrelated, and 449 were deaths. In summary, there were 2272 reports for VNS 103, 1526 reports for VNS 106, and 530 reports for VNS 1000. Within VNS 103, 33% of reports were related to device malfunction, 33% to patient complaints, and 34% to surgically managed complications. For VNS 106, 35% were related to device malfunction, 24% to patient complaints, and 41% to surgically managed complications. Lastly, for VNS 1000, 8% were device malfunction, 45% patient complaints, and 47% surgically managed complications. CONCLUSION: We present an analysis of the MAUDE data base for adverse events and complications related to VNS. It is hoped that this description of complications and literature review will help promote further improvement in its safety profile, patient education, and management of both patient and clinician expectations.

Parents' priorities for decision-making of pediatric epilepsy treatments and perceived needs for decision support in multi-ethnic Asian clinical setting: A qualitative analysis.

OBJECTIVE: To identify parents' priorities when making a decision on genetic testing and antiseizure drug (ASD) options for pediatric epilepsy and their support needs for informed decision-making in multi-ethnic Asian clinical settings. METHODS: Qualitative in-depth interviews, using a semi-structured interview guide, were conducted with purposively selected parents of pediatric patients with newly diagnosed epilepsy or known diagnosis of epilepsy (n = 26). Interviews were audio recorded and transcribed verbatim. Thematic analysis was undertaken to generate themes. RESULTS: Parents' narratives showed difficulty assimilating information, while knowledge deficit and emotional vulnerability led parents' desire to defer a decision for testing and ASDs to mitigate decisional burden. Priorities for decisions were primarily based on intuitive ideas of the treatment's risks and benefits, yet very few could elaborate on tradeoffs between risks and efficacy. Priorities outside the purview of the healthcare team, such as children's emotional wellbeing and family burden of ASD administration, were also considered important. Authority-of-medical-professional heuristic facilitated the ASD decision for parents who preferred shared rather than sole responsibility for a decision. Importantly, parents' support needs for informed decision-making were very much related to the availability of support mechanisms in post-treatment decisions owing to perceived uncertainty of the chosen ASD. CONCLUSIONS: Findings suggest that multiple priorities influenced ASD decision process. To address support needs of parents for informed decision-making, more consideration should be given to post-treatment decision support through the provision of educational opportunities, building peer support networks, and developing a novel communication channel between healthcare providers and parents.

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.

Right middle cerebral artery infarct after minor head trauma in an infant: Case report and literature review.

Ishaemic stroke (IS) in the paediatric population is extremely rare. In this age group, the occurrence of IS often concurs with underlying congenital heart disease, haematological, metabolic or immunological conditions. In contrast, the association between IS and minor head injury in children has been sparse in current literature. The authors report a case of a healthy 9-month-old male who was found to have a right middle cerebral artery territory infarct after a minor head injury. An extensive medical workup was performed, and it was negative for any previously undiagnosed co-morbidities. Given the paucity of such cases, the condition and its management are discussed in corroboration with current literature.

Review of clinical studies of perampanel in adolescent patients.

AIM: To assess the clinical trial and real-world data for adjunctive perampanel in adolescents and develop consensus recommendations to guide the use of perampanel in this population in clinical practice. METHODS: In May 2015, 15 epilepsy experts attended a Consensus Development Meeting to assess the clinical trial data for perampanel, specific to the adolescent age group (12-17 years) and develop consensus treatment recommendations. RESULTS AND DISCUSSION: Analysis of the adolescent subgroup data of three pivotal placebo-controlled, double-blind, phase 3 trials investigating perampanel in patients with ongoing focal epileptic seizures despite receiving one to three antiepileptic drugs found that perampanel 4-12 mg was superior to placebo. The tolerability profile of perampanel was generally acceptable. Adolescent patients receiving long-term treatment with perampanel in an open-label extension study maintained improvements in seizure control compared with baseline, with a favorable risk-benefit profile. A phase 2 study showed that perampanel had no clinically important effects on cognitive function, growth, and development. CONCLUSION: Perampanel is a welcome addition to the armamentarium of existing antiepileptic drugs as it represents a new approach in the management of epilepsy, with a novel mechanism of action, and the potential to have a considerable impact on the treatment of adolescents with epilepsy.

Neurology of the H1N1 pandemic in Singapore: a nationwide case series of children and adults.

Neurologic complications have long been associated with influenza. A novel strain of influenza A (H1N1) first described in humans to have outbreak potential in 2009 in Mexico went on to become the first influenza pandemic of this century. We evaluated the neurologic complications of the novel influenza A (H1N1) 2009 in children and adults admitted to all public hospitals in Singapore during the influenza A (H1N1) 2009 pandemic between May 2009 and March 2010. All patients were positive for novel H1N1 infection and presented with neurologic symptoms prior to oseltamivir treatment. Ninety-eight patients (median age 6.6 years, range 0.4-62.6) were identified; 90 % were younger than 18 years; 32 % suffered from preexisting neurological, respiratory, or cardiac disease; and 66 % presented with seizures. Of those presenting with seizures, new onset seizures were the most common manifestation (n = 40, 61.5 %), followed by breakthrough seizures (n = 18, 27.7 %) and status epilepticus (n = 7, 10.8 %). Influenza-associated encephalopathy occurred in 20 %. The majority of children (n = 88) presented with seizures (n = 63, 71.6 %), encephalopathy (n = 19, 21.6 %), and syncope (n = 4, 4.5 %). Among adults, a wider range of neurological conditions were seen, with half of them presenting with an exacerbation of their underlying neurological disease. The neurological symptoms developed at a median of 2 days after the onset of systemic symptoms. The median length of hospital stay was 3 days, and 79 % were monitored in general wards. Neurologic complications associated with the novel influenza A (H1N1) 2009 strain were generally mild and had a good outcome. They occurred more frequently in patients with underlying neurological disorders. Seizures and encephalopathy were the most common manifestations, similar to other influenza virus strains.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome may have a hypothalamus-periaqueductal gray localization.

BACKGROUND: Anatomical localization of the rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome has proved elusive. Most patients had neuroimaging after cardiorespiratory collapse, revealing a range of ischemic lesions. PATIENT DESCRIPTION: A 15-year-old obese boy with an acute febrile encephalopathy had hypoventilation, autonomic dysfunction, visual hallucinations, hyperekplexia, and disordered body temperature, and saltwater regulation. These features describe the ROHHAD syndrome. Cerebrospinal fluid analysis showed pleocytosis, elevated neopterins, and oligoclonal bands, and serology for systemic and antineuronal antibodies was negative. He improved after receiving intravenous steroids, immunoglobulins, and long-term mycophenolate. Screening for neural crest tumors was negative. CONCLUSION: Magnetic resonance imaging of the brain early in his illness showed focal inflammation in the periaqueductal gray matter and hypothalamus. This unique localization explains almost all symptoms of this rare autoimmune encephalitis.

Use of Magnesium Sulfate Infusion for the Management of Febrile Illness-Related Epilepsy Syndrome: A Case Series.

Febrile illness-related epilepsy syndrome is a catastrophic epileptic encephalopathy that is highly refractory to most antiepileptic drugs leading to high morbidity and mortality. The authors report the use of a pediatric infusion protocol of continuous intravenous magnesium sulfate for the control of seizures in 2 children with febrile illness-related epilepsy syndrome refractory to multiple antiepileptic drugs in a pediatric intensive care unit of a tertiary care children's hospital. Both patients, 2 and 16 years of age, respectively, were treated with continuous magnesium sulfate infusion. Serum magnesium concentrations ranging from 2.1 to 5 mmol/L were achieved. Seizure reduction and cessation were noted in 1 patient with magnesium more than 3.0 mmol/L. No significant adverse effects were observed. Magnesium sulfate infusions can be safely used in pediatric refractory status epilepticus. Magnesium sulfate can be considered in the management of children with febrile illness-related epilepsy syndrome.

Association of carbamazepine-induced severe cutaneous drug reactions and HLA-B*1502 allele status, and dose and treatment duration in paediatric neurology patients in Singapore.

OBJECTIVES: To determine the association between severe cutaneous drug reactions (SCDR), HLA-B*1502 allelism, carbamazepine dose and treatment duration in a Singapore paediatric population. METHOD: Case-control study of SCDR with carbamazepine and HLA-B*1502. We recruited 32 cases, 5 with Steven Johnson Syndrome/Toxic Epidermolytic Necrolysis (SJS/TEN) (2 Chinese, 3 Malay), 6 with hypersensitivity syndrome (HSS) (5 Chinese, 1 Indian), 11 with minor drug reactions (9 Chinese, 2 Malay) and 10 controls (7 Chinese, 2 Malay, 1 Indian). HLA-B*1502 allelism was assayed. HLA-B*1502 status and the type of drug reaction were compared using univariate analysis. The time-span from treatment onset to reaction and the dose-time to reaction association in the 3 groups were analysed. RESULTS: HLA-B*1502 was positive in: 5/5 (SJS/TEN), 0/6 (HSS), 1/11 (minor drug reactions) and 1/10 controls. OR for SJS/TEN in HLA-B*1502-positive patients relative to that in HLA-B*1502-negative patients was estimated by exact logistic regression to be 27.20 (95% CI 2.67 to ∞). Median treatment duration (days) until allergic reactions was 12 (range 11-13), 16 (range 10-37) and 11 (range 0-63) for SJS/TEN, HSS and minor drug reactions, respectively. Median dose at onset of reactions was 6.2 mg/kg/day (range 4.6-7.4), 9.8 mg/kg/day (range 7.7-12.2) and 6.7 mg/kg/day (range 3.6-20.0) for the 3 groups, respectively. CONCLUSIONS: HLA-B*1502 positivity increases the odds of carbamazepine-induced SCDR in Singapore children of Chinese and Malay ethnicity. Adverse drug reactions to carbamazepine occurred within 2 weeks and at low doses.

Quantifying limb movements in epileptic seizures through color-based video analysis.

This paper proposes a color-based video analytic system for quantifying limb movements in epileptic seizure monitoring. The system utilizes colored pyjamas to facilitate limb segmentation and tracking. Thus, it is unobtrusive and requires no sensor/marker attached to patient's body. We employ Gaussian mixture models in background/foreground modeling and detect limbs through a coarse-to-fine paradigm with graph-cut-based segmentation. Next, we estimate limb parameters with domain knowledge guidance and extract displacement and oscillation features from movement trajectories for seizure detection/analysis. We report studies on sequences captured in an epilepsy monitoring unit. Experimental evaluations show that the proposed system has achieved comparable performance to EEG-based systems in detecting motor seizures.

Developing a nomogram for dose individualization of phenytoin in Asian pediatric patients derived from population pharmacokinetic modeling of saturable pharmacokinetic profiles of the drug.

BACKGROUND: A population pharmacokinetic model for phenytoin in Asian pediatric patients was developed to determine the influence of concurrent medications, patient demographics, and blood biochemistry on the pharmacokinetic profile of phenytoin. METHODS: Retrospective clinical data were obtained from 66 patients (age, 1-16 years) for the determination of pharmacokinetic parameters of phenytoin using WinNonmix. Data from 49 patients (74.2%) were allocated in the "index" group, and the other 17 patients (25.8%) in the "validation" group. Models were compared by final log likelihood, mean error as a measure of bias, and root-mean-squared error as a measure of precision. RESULTS: The Michaelis-Menten constant (km) and volume of distribution (V) were fixed at 9.08 mg/L and 1.23 L/kg, respectively. The saturated elimination rate (V × Vmax) of phenytoin was then found to be 0.525 mg/kg per hour (352.9 4 mg/d for a 28.0 kg individual). Patients' body surface area (in square meter) and catalytic activities of liver enzymes aspartate aminotransferase (U/L) and alkaline phosphatase (U/L) appeared to have significant correlation with Vmax, whereas coadministrating drugs with phenytoin did not yield any significant effect. The final model for the saturated elimination rate was (Equation is included in full-text article.) In validation of the final model, the mean error was found to be -0.805 (95% confidence interval, -3.67 to 2.06), and the root-mean-squared error was 7.92 (95% confidence interval, 3.41-12.43). CONCLUSIONS: The obtained results indicated the need to consider patients' body surface area and the catalytic activities of liver enzymes aspartate aminotransferase and alkaline phosphatase when dosing phenytoin. Based on the population pharmacokinetic parameters, a nomogram was subsequently developed for dose individualization of phenytoin in Asian pediatric patients.

A retrospective study on the usage of antiepileptic drugs in Asian children from 2000 to 2009 in the largest pediatric hospital in Singapore.

PURPOSE: In light of the increasing usage of the newer antiepileptic drugs (AEDs) in other countries, we reviewed the prescribing pattern of AEDs in Singapore over the last 10 years (2000-2009). METHODS: A retrospective review of pharmacy dispensing records solicited from the only children's hospital in Singapore was performed to analyze the trend in AEDs prescribing in the last 10 years. We also examined the correlation between the serum concentrations of valproic acid (VPA), the most-prescribed AED, and seizure control. Descriptive and inferential statistical analyses were then performed on the findings. RESULTS: A total of 41 671 prescriptions on AEDs were retrieved and analyzed. Despite the introduction of the second-generation AEDs, the first generation AEDs still dominate epilepsy treatment in Asian children, with VPA being the mostly prescribed AED (about 40% of the total AEDs usage). The majority of patients (62.8%) were on monotherapy. The mean VPA serum concentration in patients with good seizure control was 68.6 µg/ml (SD = 26.4 µg/ml; range = 12.2-138.0 µg/ml), which was statistically higher than the mean VPA concentration of 57.7 µg/ml (SD = 27.1 µg/ml; range = 11.1-149.0 µg/ml) in patients with poor seizure control (p < 0.0001). CONCLUSION: With VPA being the most prescribed AED in our clinical practice, and the finding in this study that with careful classification of the patients' condition, serum concentrations of VPA generally correlate well with the seizure control, the correct dose titration of VPA with therapeutic drug monitoring is still of paramount importance.

Non-intrusive head movement analysis of videotaped seizures of epileptic origin.

In this work we propose a non-intrusive video analytic system for patient's body parts movement analysis in Epilepsy Monitoring Unit. The system utilizes skin color modeling, head/face pose template matching and face detection to analyze and quantify the head movements. Epileptic patients' heads are analyzed holistically to infer seizure and normal random movements. The patient does not require to wear any special clothing, markers or sensors, hence it is totally non-intrusive. The user initializes the person-specific skin color and selects few face/head poses in the initial few frames. The system then tracks the head/face and extracts spatio-temporal features. Support vector machines are then used on these features to classify seizure-like movements from normal random movements. Experiments are performed on numerous long hour video sequences captured in an Epilepsy Monitoring Unit at a local hospital. The results demonstrate the feasibility of the proposed system in pediatric epilepsy monitoring and seizure detection.

Markerless video analysis for movement quantification in pediatric epilepsy monitoring.

This paper proposes a markerless video analytic system for quantifying body part movements in pediatric epilepsy monitoring. The system utilizes colored pajamas worn by a patient in bed to extract body part movement trajectories, from which various features can be obtained for seizure detection and analysis. Hence, it is non-intrusive and it requires no sensor/marker to be attached to the patient's body. It takes raw video sequences as input and a simple user-initialization indicates the body parts to be examined. In background/foreground modeling, Gaussian mixture models are employed in conjunction with HSV-based modeling. Body part detection follows a coarse-to-fine paradigm with graph-cut-based segmentation. Finally, body part parameters are estimated with domain knowledge guidance. Experimental studies are reported on sequences captured in an Epilepsy Monitoring Unit at a local hospital. The results demonstrate the feasibility of the proposed system in pediatric epilepsy monitoring and seizure detection.

Rapid oscillatory activity in delta brushes of premature and term neonatal EEG.

We compared frequency and power of neonatal EEG delta brush rapid oscillatory activity (ROA) using multiple band frequency analysis (MBFA) in three groups; pre-term (PT, post-conceptional age 33-35.6 weeks, n=5); full-term (FT, 39.4-40.6 weeks, n=5) and pre-term or full-term with phenobarbital exposure (PB, n=5). Mean number of delta brushes analyzed was 29.4 (range 26-47) in PT, 20.8 (14-33) in FT and 20 (7-37) in PB. Mean frequency+/-standard deviation (s.d.) was 16.9+/-2.1 Hz (range 15-20 Hz) in PT, 17.3+/-1.9 Hz (15-20 Hz) in FT and 16.1+/-1.6 Hz (14-19 Hz) in PB. Mean power+/-s.d. was 22.9+/-6.2 microV(2) (range 16-39 microV(2)) in PT, 11.9+/-4.1 microV(2) (7-19 microV(2)) in FT and 17.1+/-6.2 microV(2) (9-26 microV(2)) in PB. Power was significantly higher in PT than FT (p<0.005). Power after merging PB into respective PT (PT', n=8) and FT (FT', n=7) groups, remained significantly higher in PT' (mean+/-s.d. 21.8+/-7.4 microV(2)) than FT' (11.4+/-3.6 microV(2)) (p<0.05). We characterise ROA in delta brushes in maturing neonates using MBFA, which may provide additional information for assessing future seizure recurrence and epilepsy risk.

Elevated thyroid peroxidase antibodies with encephalopathy in MELAS syndrome.

Both the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) and Hashimoto's encephalopathy can present with nonspecific encephalopathy. Hashimoto's encephalopathy is an association of steroid-responsive encephalopathy with elevated thyroid peroxidase antibodies. Steroid-responsive encephalopathy, however, is not characteristic of the MELAS syndrome, which typically presents with stroke-like episodes and lactic acidosis in cerebrospinal fluid and blood. Here, a patient is described with goiter, recurrent encephalopathy and elevated thyroid peroxidase antibodies who apparently responded to steroid therapy; however, magnetic resonance imaging was atypical for Hashimoto's encephalopathy, and she was diagnosed with MELAS syndrome. This syndrome can present with apparent steroid-responsive encephalopathy and elevated thyroid peroxidase antibodies, mimicking Hashimoto's encephalopathy, and should be suspected if lactic acidosis is present and typical features are detected on magnetic resonance imaging.