Case report: Dihydropyridine receptor (CACNA1S) congenital myopathy, a novel phenotype with early onset periodic paralysis.

Introduction: CACNA1S related congenital myopathy is an emerging recently described entity. In this report we describe 2 sisters with mutations in the CACNA1S gene and the novel phenotype of congenital myopathy and infantile onset episodic weakness. Clinical description: Both sisters had neonatal onset hypotonia, muscle weakness, and delayed walking. Episodic weakness started in infancy and continued thereafter, provoked mostly by cold exposure. Muscle imaging revealed fat replacement of gluteus maximus muscles. Next generation sequencing found the missense p.Cys944Tyr variant and the novel splicing variant c.3526-2A>G in CACNA1S. Minigene assay revealed the splicing variant caused skipping of exon 28 from the transcript, potentially affecting protein folding and/or voltage dependent activation. Conclusion: This novel phenotype supports the notion that there are age related differences in the clinical expression of CACNA1S gene mutations. This expands our understanding of mutations located in regions of the CACNA1S outside the highly conserved S4 segment, where most mutations thus far have been identified.

A 5-Year-Old Palestinian Bedouin Girl with Repeated Self-Induced Injuries to the Digits, a Diagnosis of Congenital Insensitivity to Pain, and Anhidrosis.

BACKGROUND Congenital insensitivity to pain with anhidrosis (CIPA), also referred to as hereditary sensory and autonomic neuropathy type IV, is a rare autosomal recessive disease caused by mutations in the NTRK1 gene. The inability to feel pain and temperature often leads to repeated severe and unintentional self-inflicted injuries; these can result in severe complications, as patients heal slowly from skin and bone injuries. This case report describes a 5-year-old Palestinian girl with self-inflicted injury to the digits, a dislocated distal inter-phalangeal joint of the left big toe, and a diagnosis of CIPA. CASE REPORT A 5-year-old girl, a daughter of related Palestinian Bedouin parents, presented with a chronic unhealed wound over the planter surface of the left foot. Painless repetitive minor traumata over the same area badly affected wound healing and this led to wound dehiscence and dislocation of the distal inter-phalangeal joint of the left big toe. Surgical fixation of the dislocated joint along with intravenous antibiotics and close follow-up resulted in eventual improvement and near complete wound healing despite the obviously slow healing process. The girl also displayed evidence of unintentional self-inflicted injury, which within the overall clinical context warranted a clinical suspicion of CIPA. This was confirmed by genetic testing for the presence of a homozygous frameshift mutation in the NTRK1 gene (c.1842_1843insT; p.Pro615Serfs*12). CONCLUSIONS This case report shows that a physician should have a low threshold of suspicion to investigate for CIPA when managing children with multiple unintentional self-inflicted injuries, anhidrosis, and pain insensitivity, mainly through genetic testing to detect mutations in the NTRK1 gene.

Social impairment in children with epilepsy assessed by the social responsiveness scale.

Children with epilepsy are at risk for impaired social cognition and autism. We aimed at evaluating the utility of the social responsiveness scale (SRS) for assessment of social impairment in these children. Prospective study; the SRS was applied to a group of children with epilepsy and a healthy control group. Intellectual disability in the epilepsy group was assessed utilizing adapted versions of the Wechsler Intelligence and adaptive behavior scales. One hundred and one children with epilepsy and 92 healthy children were included. The majority of children in both groups had normal SRS scores. Significant differences were identified in children with high total scores indicating significant deficiencies in reciprocal social behavior; high scores were found in 16% of children with epilepsy versus 7% of normal children, p < .05, particularly involving social communication, p < .05. Intellectual disability was identified in 42% of children with epilepsy, particularly processing speed index, p < .001. Intellectual disability had a significant effect on total scores, p = .016. Children with epilepsy have increased risk of social impairments. Social impairments are more likely in the presence of intellectual disability. The SRS is a quick identification tool that can be employed in the outpatient setting.

Dental health status and hygiene in children with cerebral palsy: A matched case-control study.

BACKGROUND: Children with cerebral palsy (CP) are at risk for oral pathology and parafunctional habits, and are reliant on caregivers for oral hygiene. AIM: To evaluate oral hygiene habits and oral examination findings among a group of children with CP and a healthy age- and gender-matched control group. DESIGN: A comparative, cross-sectional study, consisting of a questionnaire component and a standard dental examination component, each applied to both groups. RESULTS: Eighty-three children with CP and 84 healthy children were included. Parents of children with CP were more likely to be of low educational level and lack a professional line of occupation (P < .05). Children with CP were less likely to be responsible for oral hygiene maintenance, adhere to toothbrushing, or receive procedural dental care (P < .001). Food packing and drooling were significantly more likely in children with CP. Malocclusion type III was more prevalent among children with CP, as was higher gingival index and gingival enlargement index-horizontal component (P < .001). There were no differences in caries experience between the CP and control groups. CONCLUSIONS: Children with CP have suboptimal oral hygiene habits, limited access to procedural dental care, higher parafunctional habits, and increased periodontal pathology.

Take two: Utility of the repeat skeletal muscle biopsy.

INTRODUCTION: The utility of repeat muscle biopsy has not been adequately evaluated. METHODS: A retrospective review was undertaken of 144 repeat muscle biopsies performed from 1980 to 2017. Repeat biopsy was considered clinically relevant if it provided a new diagnosis, changed the existing diagnosis, or led to treatment changes or further investigations. RESULTS: Repeat biopsy was abnormal in 118 cases, different from the initial biopsy in 67 cases, and specific in 40 cases. Factors with a significant effect on clinical relevance of the repeat biopsy (P < 0.05) were an abnormal, specific, or inflammatory initial biopsy, proximal muscle weakness, absence of myalgia, and a repeat biopsy that is different, specific, or consistent with polymyositis or inclusion body myositis. CONCLUSIONS: Utility of repeat biopsy was limited to weak patients whose initial biopsy showed inflammatory myositis. Ongoing advances in the diagnosis of immune inflammatory myopathies have led to evolution of the role of repeat biopsy. Muscle Nerve, 2019.

The vagal nerve stimulation outcome, and laryngeal effect: Otolaryngologists roles and perspective.

INTRODUCTION: Epilepsy is one of the most common neurologic disorders. Vagus nerve stimulation (VNS), first investigated in 1938 and subsequently studied as a potential therapy for epilepsy. The FDA approved the use of VNS in 1997 as an adjunctive non-pharmacologic symptomatic treatment option for refractory epilepsy for adults and adolescents over 12years. VNS can cause laryngeal and voice side effects that can be managed by otolaryngologists safely and effectively. OBJECTIVES: This study is to review the outcomes of vagal nerve stimulator (VNS) implantation in terms of the surgical procedures, complications, seizure frequency, and the clinical effect on larynx and vocal folds motion. METHODS: Series of thirty consecutive patients who had VNS implantation between 2007 and 2014 were recruited. Seizure-frequency outcome, surgical complications and device adverse effects of VNS were retrospectively reviewed. Additional evaluation included use of the Voice Handicap Index and Maximum Phonation Time (MPT) were conducted before and after the implantation. Videolaryngoscopy was used to evaluate the vocal fold mobility before and after the VNS implantation. RESULTS: Seizure frequency reduction over a minimum of 2years of follow up demonstrated: 100% in seizure frequency reduction in 1 patient, drastic reduction in seizure frequency (70-90%) in 9 patients, a good reduction in terms of seizure frequency (50%) in 8 patients, a 30% reduction in 5 patients, no response in 6 patients, and 1 patient had increased frequency. The most commonly reported adverse effects after VNS activation were coughing and voice changes with pitch breaks, as well as mild intermittent shortness of breath in 33% of patients. For those patients secondary supraglottic muscle tension and hyper function with reduced left vocal fold mobility were noticed on videolaryngoscopy, though none had aspiration problems. Surgical complications included a wound dehiscence in one patient (3%) which was surgically managed, minor intra-operative bleeding 3%; a superficial wound infection in one patient (3%) which was treated conservatively, none of the complications necessitated VNS removal. CONCLUSIONS: VNS appears to be an effective non-pharmacologic adjuvant therapy in patients with medically refractory seizures. With the favorable adverse-effect profile previously described, VNS is generally well tolerated and of a great benefit to such patients. Laryngeal side effects, of which hoarseness being of the greatest repetition, are the most common after the VNS implantation. VNS can affect the voice and reduced vocal cord motion on the implantation side with secondary supraglottic muscle tension. Otolaryngologists are not only capable of performing VNS implantation, but can also manage surgical complications, assess laryngeal side effects and treat them as needed.

Novel mutations in WWOX, RARS2, and C10orf2 genes in consanguineous Arab families with intellectual disability.

Intellectual disability is a heterogeneous disease with many genes and mutations influencing the phenotype. Consanguineous families constitute a rich resource for the identification of rare variants causing autosomal recessive disease, due to the effects of inbreeding. Here, we examine three consanguineous Arab families, recruited in a quest to identify novel genes/mutations. All the families had multiple offspring with non-specific intellectual disability. We identified homozygosity (autozygosity) intervals in those families through SNP genotyping and whole exome sequencing, with variants filtered using Ingenuity Variant Analysis (IVA) software. The families showed heterogeneity and novel mutations in three different genes known to be associated with intellectual disability. These mutations were not found in 514 ethnically matched control chromosomes. p.G410C in WWOX, p.H530Y in RARS2, and p.I69F in C10orf2 are novel changes that affect protein function and could give new insights into the development and function of the central nervous system.

Vagus nerve stimulation therapy in a developing country: a long term follow up study and cost utility analysis.

PURPOSE: To evaluate clinical outcomes, quality-adjusted life years (QALY), cost effectiveness and cost utility associated with VNS therapy in children with refractory epilepsy in a developing country. METHODS: Retrospective review of all children who underwent VNS implantation at King Abdullah University Hospital and Jordan University Hospital in Jordan. RESULTS: Twenty eight patients (16 males) had implantation of the VNS therapy system between the years 2007 and 2011. Mean age at implantation was 9.4 years. Mean duration of epilepsy prior to implantation was 6.5 years. The most common seizure type was generalized tonic clonic seizures. Fifteen patients showed a 50% or more reduction in seizure frequency. There was a significant reduction in total number of seizures (p=0.002) and emergency room (ER) visits (p=0.042) after VNS therapy. Atonic seizures were more likely to respond than generalized tonic clonic seizures, p=0.034. Direct hospital costs prior to VNS implantation were analyzed in relation to ER visits and intensive care unit (ICU) admissions. Cost savings per patient did reduce the financial burden of the device by about 30%. There was a QALY gain per lifetime of 3.78 years for children and 1 year for adolescents. CONCLUSION: Response to VNS implantation in Jordan was favorable and similar to what has been previously reported. QALY gain and cost per QALY analysis were encouraging. Cost savings were related to reduction in seizure severity. In circumstances of limited resources as in developing countries, targeting patients with frequent utilization of health services would improve cost effectiveness.

Complementary and alternative medicine use in a pediatric neurology clinic.

To evaluate the frequency and determinants of complementary and alternative medicine (CAM) use in children attending a pediatric neurology clinic in North Jordan, a parent completed questionnaire survey of children attending the pediatric neurology clinic at King Abdullah University Hospital from March to July 2008 was conducted. A review of 176 completed questionnaires showed that 99 parents (56%) had used CAM for their child's specific neurological illness. The most common modalities were prayer/reciting the Quran (77%), religious healers (30%), massage with olive oil (32%), and consumption of honey products (29%). The most common reason was religious beliefs in 68%. None reported lack of trust in conventional medicine as the reason behind seeking CAM. Factors significantly associated with CAM use were speech delay, belief in its usefulness, father's age more than 30 years, and mothers with education less than high school. CAM had a supplementary role in relation to traditional western medicine use.

Idiopathic hypertrophic pachymeningitis in a child with hydrocephalus.

Idiopathic hypertrophic pachymeningitis is a rare but increasingly recognized disorder characterized by diffuse thickening of the dura mater of unknown etiology. The inflammation usually involves the cranial or spinal dura mater, with resultant neurologic deficits. Although it is reported primarily in adults, there is one previous report describing the condition in a child. Described here is the case of a child who presented at the age of 3.5 years with idiopathic hypertrophic pachymeningitis involving the entire central nervous system, with poor response to steroids, cyclophosphamide, and intraventricular cytarabine.

Treatment of sialorrhea in children with cerebral palsy: a double-blind placebo controlled trial.

OBJECTIVES: To prospectively study the efficacy and safety of intraparotid gland injection of Botulinum neurotoxin serotype A (Dysport) for the treatment of sialorrhea (drooling) in children with cerebral palsy (CP). PATIENTS AND METHODS: Twenty-four children, ages 21 months to 7 years, were recruited and randomized to receive either treatment with 100U Botulinum toxin or placebo. Rating scales for the frequency and severity of drooling were performed at the time of injection, at 1 month, and at baseline prior to the second injection. A second set of injections of either 140U of drug or placebo was given 4 months later, and the same rating scales were used. Eight patients declined the second injection. Due to high dropouts in the placebo group in second set of injections, statistical analysis was performed for the results of the initial injection only. RESULTS: Scores of the median frequency (p=0.034) and severity (p=0.026) of drooling were reduced in the treatment group. Median total score also declined in the treatment group (p=0.027). After the second injection, five out of nine patients injected with the drug showed a decline in the total score; including three patients who did not respond to the first injection. Only two patients experienced transient increase in drooling after the treatment with the drug. CONCLUSION: Botulinum toxin is an effective and safe treatment option for drooling in children with CP.