Clinical features and outcomes in children with seronegative autoimmune encephalitis.

AIM: To characterize the presenting features and outcomes in children with seronegative autoimmune encephalitis, and to evaluate whether scores at nadir for the Modified Rankin Scale (mRS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) or its paediatric-specific modification (ped-CASE) are predictive of outcomes. METHOD: This observational study included children younger than 18 years of age with seronegative autoimmune encephalitis. Demographics and clinical data were collected. The mRS and CASE/ped-CASE scores were used to evaluate disease severity. Descriptive statistics and logistic regression were used for data analysis and to evaluate associations between scale scores and outcomes. RESULTS: Sixty-three children were included (39 [62%] females, median age 7 years, interquartile range [IQR] 4 years 1 months-11 years 6 months), with follow-up available for 56 out of 63 patients (median follow-up 12.2 months, IQR 13.4-17.8). The most frequent presenting neurological manifestation was encephalopathy (81%). Median CASE/ped-CASE and mRS scores at nadir were 12.0 (IQR 7.0-17.0) and 1.0 (IQR 0-2.0) respectively. Thirty-three patients (59%) had persistent neurological deficits at follow-up. Both scoring systems suggested good functional recovery (mRS score ≤2, 95%; CASE/ped-CASE score <5, 91%). CASE/ped-CASE score was more likely than mRS to distinguish children with worse outcomes. INTERPRETATION: Children with seronegative autoimmune encephalitis are likely to have neurological deficits at follow-up. CASE/ped-CASE is more likely to distinguish children with worse outcomes than MRS.

Expanding the phenome and variome of skeletal dysplasia.

PURPOSE: To describe our experience with a large cohort (411 patients from 288 families) of various forms of skeletal dysplasia who were molecularly characterized. METHODS: Detailed phenotyping and next-generation sequencing (panel and exome). RESULTS: Our analysis revealed 224 pathogenic/likely pathogenic variants (54 (24%) of which are novel) in 123 genes with established or tentative links to skeletal dysplasia. In addition, we propose 5 genes as candidate disease genes with suggestive biological links (WNT3A, SUCO, RIN1, DIP2C, and PAN2). Phenotypically, we note that our cohort spans 36 established phenotypic categories by the International Skeletal Dysplasia Nosology, as well as 18 novel skeletal dysplasia phenotypes that could not be classified under these categories, e.g., the novel C3orf17-related skeletal dysplasia. We also describe novel phenotypic aspects of well-known disease genes, e.g., PGAP3-related Toriello-Carey syndrome-like phenotype. We note a strong founder effect for many genes in our cohort, which allowed us to calculate a minimum disease burden for the autosomal recessive forms of skeletal dysplasia in our population (7.16E-04), which is much higher than the global average. CONCLUSION: By expanding the phenotypic, allelic, and locus heterogeneity of skeletal dysplasia in humans, we hope our study will improve the diagnostic rate of patients with these conditions.

Gaucher disease. Unusual presentation and mini-review.

We aim to describe an 8-year-old boy with an unusual clinical presentation of Gaucher disease (GD). Gaucher disease is a progressive lysosomal storage disorder due to deficiency of the specific enzyme glucocerebrosidase with varying clinical features, but often involving the monocytes-macrophages systems. This child ran a progressive course with a devastating outcome. Three distinct GD subtypes have been described with varying clinical features based on the presence or absence of neurologic involvement. Gaucher disease diagnosis is obtained via: enzyme activity assay, gene mutation study, bone marrow aspiration in addition to multiple other tests that have been successfully used in diagnosis of cases of GD. Treatment modalities include enzyme replacement treatment, substrate reduction therapy, bone marrow transplantation, blood transfusion, and surgery are available management modalities for GD. Gaucher disease is a chronic disease requiring a multidisciplinary team approach with regular follow up with multiple subspecialties.

Ineffectiveness of topiramate and levetiracetam in infantile spasms non-responsive to steroids. Open labeled randomized prospective study.

OBJECTIVE: To compare the effectiveness of 2 novel antiepileptic drugs, topiramate and levetiracetam, as a second line treatment for infantile spasm when oral steroids fail. METHODS: Forty infants under 2 years with clinically- and EEG-proven infantile spasms that did not respond to prednisone (2mg/kg/day in 2 divided doses) were recruited and randomized into 2 groups. They were randomly assigned to either topiramate (group 1; 1mg/kg/day for 3 days then increased by 1mg/kg/day every third day up to 6mg/kg/day) or levetiracetam (group 2; 10mg/kg/day for 5 days and then increased by 10mg/kg/day every 5 days up to 60mg/kg/day). The study was conducted in the Pediatric Neurology Department at the National Neuroscience Institute of King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia between January 2008 and December 2010. RESULTS: Of the 20 patients included in the final data analysis, 11 (55%) were administered topiramate and 9 (45%) levetiracetam. Eighteen patients did not respond to the first drug, and subsequently to the other drug when crossed-over. Two patients with infantile spasm responded to either one drug without crossover. Their EEGs improved with time. CONCLUSION: The present study demonstrated the ineffectiveness of topiramate and levetiracetam suggesting current treatment modalities are grossly inadequate underscoring the urgent need for more research efforts to overcome current deficiencies. Two patients with cryptogenic infantile spasm responded to treatment suggesting the potential for treatment of such patients with these 2 drugs, and merits further multicenter investigation.

A case of extreme prematurity and delayed diagnosis of pyridoxine-dependent epilepsy.

Pyridoxine-dependent epilepsy presents early in life, even in utero. It is usually refractory to conventional antiepileptic medications and responds only to lifelong pyridoxine supplementation. Seizures are usually generalized tonic clonic. We report a 3-year-old child that was born prematurely at 25 weeks of gestation. He presented with abnormal movements in the second month of life. At 10 months of age he presented with status epilepticus, which was refractory to multiple antiepileptic medications and was controlled with intravenous pyridoxine. An elevated level of a-aminoadipic semialdehyde excretion in the urine supported the diagnosis of pyridoxine-dependent epilepsy. Subsequently, a c.1195G>C homozygous mutation in the 5q31 aldehyde dehydrogenase 7A1 gene was confirmed. This case calls for considering pyridoxine-dependent epilepsy and its early management in cases with resistant seizures; even in the presence of extreme prematurity with its neurological consequences.

Incidence of kidney stones with topiramate treatment in pediatric patients.

PURPOSE: We ran this study to assess the incidence of nephrolithiasis in a group of children on topiramate (TPM) therapy for at least 1 year. METHODS: In this retrospective observational surveillance study, we reviewed the medical charts of children on TPM for at least 1 year seen at the pediatric neurology department during the period from 2005 to 2010 at King Fahad Medical City. Children with a normal baseline ultrasound report were included. Follow-up ultrasound reports after at least 1 year were collected. However, patients with any evidence of chronic illness or medications that may affect the kidney functions in addition to those who are not compliant with the prescribed dose were excluded. Family history of renal stones, symptoms suggestive of urologic disorders, and comorbidities were recorded. KEY FINDINGS: Medical charts of 96 children on TPM with a mean age of 6.9 (±3.8) years were reviewed; 52 (54.2%) of the children were male. The follow-up ultrasound showed that five children (5.2%) had developed kidney stones. The occurrence of kidney stones was found in four female patients (80%) versus one male (20%) (p > 0.05). SIGNIFICANCE: Long-term use of TPM may result in increased incidence of asymptomatic kidney stones in the pediatric population. Hence, routine baseline and follow-up ultrasound of the urinary system should be recommended during the use of TPM in children.

Moyamoya Disease in a Six Month Caucasian Female.

Moyamoya disease (MMD) is a progressive cerebral arteriopathy characterized by stenosis and/or occlusion of the internal carotid arteries and the arteries around the Circle of Willis, with the development of "moyamoya" vessels, which are an attempt at revascularization at the base of the brain. In this paper we describe a 6 month, 3-week-old girl who presented with seizures and strokes due to moyamoya disease. The diagnosis of early onset MMD was made due to the magnetic resonance angiography results showing severe stenosis of the terminal/supraclinoid carotid arteries bilaterally with moyamoya vessels, and a completely novel de novo mutation in the RNF213 gene. She underwent bilateral encephaloduroarteriosynangiosis (EDAS) five months after her initial presentation and she did pretty well subsequently. She has shown no episodes suggestive of further strokes up to one year after surgery.

Menkes disease presenting with epilepsia partialis continua.

Aim. We aim to describe a female patient with Menkes disease who presented with epilepsia partialis continua. Case Presentation. Seventeen-months-old Saudi infant was presented with repetitive seizures and was diagnosed to have epilepsia partialis continua. Discussion. Menkes disease (OMIM: 309400) is considered a rare, X-linked recessive neurodegenerative disorder resulting from a mutation in the gene coding for the copper transporting ATPase (ATP7A). Affected individuals usually present with kinky hair, skeletal changes, prolonged jaundice, hypothermia, developmental regression, decreased tone, spasticity, weakness, and therapy resistant seizures. Conclusion. Raising awareness of abnormal presentation of this rare disease may help in the control of seizures through subcutaneous copper supplementation.

Complications of intrathecal baclofen pump: prevention and cure.

Increasingly, spasticity is managed with surgically implanted Intrathecal Baclofen pumps. Intrathecal Baclofen pump revision surgery unrelated to programmable pump end-of-life is not uncommon, requiring special attention during pre-, intra-, and postoperative management. We aimed to identify and describe complications of Intrathecal Baclofen pump as well as to report avoidance and management of complications. Methods and Materials. Through 2002-2006, at the department of neurosurgery, Henry Ford and Oakwood Health Systems, Intrathecal Baclofen pumps were implanted in 44 patients: 24 children versus 20 adults; 30 "primary-implant-patients"; 14 "revision-only patients". We evaluated reasons for revision surgeries and diagnostic workup requirements. Results. Eight primary-implant-patients required 14 revisions and 7 of revision-only patients needed 13 procedures. Seven patients with slowly increasing baclofen-resistant spasticity had either (i) unsuspected pump-catheter connector defects, (ii) an X-ray-documented pump-catheter connector defect, (iii) X-ray-demonstrated fractured catheter with intrathecal fragment. Implant infections occurred in 4 cases. Scintigraphy revealed occult CSF leakage N=1 and intrinsic pump failure N=1. Conclusion. Intrathecal Baclofen pumps, although very gratifying, have a high, technique-related complication incidence during implant life. Meticulous technique, high clinical suspicion, appropriate workup, and timely surgical management can reduce surgical complications of Intrathecal Baclofen pump implantation.