Consanguinity in patients with mesial temporal lobe epilepsy due to hippocampal sclerosis in a Saudi population.

OBJECTIVE: To investigate if there is an association between consanguinity and hippocampal sclerosis (HS) in the Saudi population. METHODS: A retrospective case-control study was conducted by assessing the prevalence of consanguinity in patients with pathologically proven HS, who underwent epilepsy surgery at King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia, between January 2004 and December 2015. We reviewed the medical records to extract data, which included; age, gender, duration of epilepsy, history of febrile seizure, family history of epilepsy in a first or second-degree relative, and pathology reports. RESULTS: A total of 120 patients, out of which 40 patients (65% male) having mesial temporal lobe epilepsy due to HS, and 80 controls (56% male) with cryptogenic epilepsy, were identified. Twenty-two patients (53.5%) in the HS group had a history of consanguinity. In the control group, 30 patients (37.5%) had a history of consanguinity. The odds ratio was 2.04 (95% confidence interval = 0.94 - 4.4, p=0.052). A family history of epilepsy was found in 28% of the patients with HS and 32.5% cryptogenic epilepsy. Only 8 patients (19.5%) with HS reported a history of febrile seizure. CONCLUSION: Our retrospective case-control study suggests that consanguinity might increase the likelihood of developing HS.

Autozygome and high throughput confirmation of disease genes candidacy.

PURPOSE: Establishing links between Mendelian phenotypes and genes enables the proper interpretation of variants therein. Autozygome, a rich source of homozygous variants, has been successfully utilized for the high throughput identification of novel autosomal recessive disease genes. Here, we highlight the utility of the autozygome for the high throughput confirmation of previously published tentative links to diseases. METHODS: Autozygome and exome analysis of patients with suspected Mendelian phenotypes. All variants were classified according to the American College of Medical Genetics and Genomics guidelines. RESULTS: We highlight 30 published candidate genes (ACTL6B, ADAM22, AGTPBP1, APC, C12orf4, C3orf17 (NEPRO), CENPF, CNPY3, COL27A1, DMBX1, FUT8, GOLGA2, KIAA0556, LENG8, MCIDAS, MTMR9, MYH11, QRSL1, RUBCN, SLC25A42, SLC9A1, TBXT, TFG, THUMPD1, TRAF3IP2, UFC1, UFM1, WDR81, XRCC2, ZAK) in which we identified homozygous likely deleterious variants in patients with compatible phenotypes. We also identified homozygous likely deleterious variants in 18 published candidate genes (ABCA2, ARL6IP1, ATP8A2, CDK9, CNKSR1, DGAT1, DMXL2, GEMIN4, HCN2, HCRT, MYO9A, PARS2, PLOD3, PREPL, SCLT1, STX3, TXNRD2, WIPI2) although the associated phenotypes are sufficiently different from the original reports that they represent phenotypic expansion or potentially distinct allelic disorders. CONCLUSIONS: Our results should facilitate the timely relabeling of these candidate disease genes in relevant databases to improve the yield of clinical genomic sequencing.

Atypical Neurologic Phenotype and Novel SLC30A10 Mutation in Two Brothers with Hereditary Hypermanganesemia.

Manganese (Mn) is an essential element in trace quantity but large amounts are toxic. A novel hereditary disorder encompassing high blood Mn levels, dystonia, polycythemia, distinctive T1 hyperintense signals in the basal ganglia on magnetic resonance imaging (MRI) brain, and chronic liver disease was recently described. The disorder is caused by mutations in a Mn transporter encoding gene SLC30A10. We are reporting the clinical features of this rare disorder in two Saudi brothers. The older brother presented with progressive gait difficulties, hypotonia, intermittent dystonia, polycythemia, and characteristic T1-hyperintense lesions on MRI brain. SLC30A10 sequencing identified a novel missense mutation. The younger brother was identified in presymptomatic phase on family screening. Chelation therapy with disodium calcium edetate (ethylenediaminetetraacetic acid, EDTA) led to stabilization of gait, reduction in Mn levels, and resolution of polycythemia. We wish to highlight the atypical neurologic presentation, a novel missense mutation, and beneficial effect of EDTA in this rare disease.

Cerebral venous thrombosis after immune thrombocytopenic purpura and anti-D immune globulin therapy.

Cerebral venous thrombosis has multiple etiologies and a wide variety of clinical manifestations. This article reports on a young girl who developed cerebral venous thrombosis after intravenous anti-D immune globulin therapy for immune thrombocytopenic purpura. In this case, venous infarction was manifested by an unusual pattern of restricted diffusion limited to the corpus callosum. The cause of cerebral venous thrombosis in this patient may be related to both immune thrombocytopenia and immunoglobulin therapy.

Ketogenic Diet Decreases Emergency Room Visits and Hospitalizations Related to Epilepsy.

Background. Approximately, one-third of patients with epilepsy are refractory to pharmacological treatment which mandates extensive medical care and imposes significant economic burden on patients and their societies. This study intends to assess the impact of the treatment with ketogenic diet (KD) on reducing seizure-related emergency room visits and hospitalizations in children with refractory epilepsy. Methods. This is a retrospective review of children treated with the KD in one tertiary center. We compared a 12 months' period prior to KD with 12 months after the diet was started in regard to the number of emergency department (ED) visits, hospitalizations, and hospital days as well as their associated charges. Results. 37 patients (57% males) were included. Their ages at time of KD initiation were (4.0 ± 2.78) years. Twelve months after the KD initiation, the total number of ED visits was reduced by 36% with a significant decrease of associated charges (p = 0.038). The number of hospital admissions was reduced by 40% and the number of hospital days was reduced by 39%. The cumulative charges showed net cost savings after 9 months when compared to the prediet baseline. Conclusion. In children with refractory epilepsy, treatment with the ketogenic diet reduces the number of ED visits and hospitalizations and their corresponding costs.

Vagus nerve stimulation for refractory epilepsy: experience from Saudi Arabia.

BACKGROUND: Vagus nerve stimulation (VNS) has been approved for the treatment of refractory partial epilepsy in adults and children over 12 years of age. Later on, its application expanded to include younger children and other types of epilepsy. We report our experience with this treatment modality for refractory epilepsy in Saudi Arabia. DESIGN AND SETTINGS: Open-label, uncontrolled, retrospective study of patients with refractory epilepsy, who were treated with VNS in a tertiary care hospital from January 2010 to June 2013. PATIENTS AND METHODS: Collected data included 26 patients' demographics, epilepsy characteristics, seizure frequency, and treatment history. Patients with a follow-up duration of minimum 12 months were included in the analysis. The examined outcome measures were seizure reduction rates, antiepileptic drugs (AEDs) burden, and impact on patients' quality of life (QOL). RESULTS: Onset of seizures was from birth to 30 years. Patients' ages at VNS implantation ranged from 4 to 38 years (18.9 [8.7] years). Epilepsy was classified as focal in 8 patients (30%), multifocal in 9 patients (35%), and generalized in 9 patients (35%). The average number of AEDs failed before VNS was 4.2 (1.4). Greater than 50% seizure reduction was achieved in 50% of patients at 3 months, 67% at 6 months, 73% at 12 months, and 78% at 24 months. There was no significant reduction in AEDs burden during the same period. Subjective QOL improvement was reported by 72% of patients at 3 months, 83% at 6 months, 78% at 12 months, and 73% at 24 months after VNS. Minor adverse effects were reported in 27% of patients. One patient had the device replaced due to malfunction. CONCLUSION: The experience with VNS in a single center in Saudi Arabia confirms that it is a safe and effective adjunctive therapy for refractory epilepsy in adult and pediatric patients.

Cerebellar swelling due to familial hemophagocytic lymphohistiocytosis: An unusual presentation.

BACKGROUND: Cerebellar swelling with obstructive hydrocephalus is a rare but life threatening condition, associated with different etiologies, familial hemophagocytic lymphohistiocytosis (HLH) being rarely one of them. PATIENT: 2-year-7-month old boy presented with irritability, cerebellar dysfunction, and somnolence. Brain MRI showed marked diffuse cerebellar swelling and obstructive hydrocephalus with mild tonsillar herniation. Laboratory testing revealed pancytopenia, elevated liver enzymes, elevated ferritin and triglycerides levels and decreased fibrinogen. The diagnosis of familial HLH was confirmed by the presence of homozygous missense mutation of Syntaxin 11 gene. The child was treated with HLH-2004 protocol of chemotherapy followed by allogenic stem cell transplantation. His neurological condition improved significantly after treating the underlying disease. CONCLUSION: Cerebellar swelling is a rare manifestation of familial HLH. High degree of clinical suspicion may allow a timely diagnosis and appropriate therapy.

Ketogenic diet efficacy in the treatment of intractable epileptic spasms.

OBJECTIVE: To determine the efficacy of the ketogenic diet in controlling epileptic spasms after failing traditional antiepileptic medication therapy. METHODS: This is a prospective, case-based study of all infants with epileptic spasms who were referred for treatment with the ketogenic diet at our hospital between 2009 and 2012. All subjects continued to have epileptic spasms with evidence of hypsarrhythmia or severe epileptic encephalopathy on electroencephalography despite appropriate medication treatments. The diet efficacy was assessed through clinic visits, phone communications, and electroencephalography. Quality of life improvement was charted based on the caregiver's perspective. RESULTS: Twenty infants (15 males) were included in the study. The mean age at seizure onset was 4.5 months. Age at ketogenic diet initiation was 0.3 to 2.9 years (mean 1.20, standard deviation 0.78). Fifteen patients had epileptic spasms of unknown etiology; three had perinatal hypoxic ischemic encephalopathy, one had lissencephaly, and one had STXBP1 mutation. Fifteen infants failed to respond to adrenocorticotropin hormone and/or vigabatrin before going on the ketogenic diet. Three months after starting the diet, >50% seizure reduction was achieved in 70% of patients (95% CI 48-86). These results were maintained at 6- and 12-month intervals. All eight of the patients followed for 24 months had >50% seizure reduction (95% CI 63-100). At least 90% seizure reduction was reported in 20% of patients at 3 months (95% CI 7-42), 22% (95% CI 8-46) at 6 months, and 35% (95% CI 17-59) at 12 months. The majority of patients (63%) achieved improvement of their spasms within 1 month after starting the diet. Sixty percent of patients had electroencephalographic improvement. All caregivers reported improvement of the quality of life at the 3-month visit (95% confidence interval 81-100). This ratio was 94% at 6 months (95% CI 72-99) and 82% at 12 months (95% CI 58-95). CONCLUSION: The ketogenic diet is a safe and potentially effective method of treatment for patients with epileptic spasms, especially those who do not respond to customary medication therapies.

The role of epilepsy surgery in the treatment of childhood epileptic encephalopathy.

Children with epileptic encephalopathy often have global impairment of brain function and frequent intractable seizures, which contribute further to their developmental disability. Many of these children have identifiable brain lesion on neurological imaging. In such cases, epilepsy surgery may be considered as a treatment option despite the lack of localized epileptic pattern on electroencephalogram (EEG). In this paper, we summarize the clinical features of epileptic encephalopathy syndromes and review the reported literature on the surgical approach to some of these disorders.

Incidental neuroimaging findings in nonacute headache.

We studied the frequency and consequences of incidental neuroimaging findings in 400 otherwise healthy, nonacute pediatric headache patients through a retrospective, cross-sectional analysis. We excluded patients with currently recommended clinical criteria to consider diagnostic neuroimaging. We categorized neuroimaging results as normal, remarkable without clinical action, remarkable with clinical follow-up action, and abnormal. One hundred eighty-five of 400 patients (46%) had neuroimaging. Of these, 78.4% of neuroimaging studies were normal, and none was considered abnormal. Also, 21.5% had remarkable findings in the neuroradiology report. The frequency and types of all incidental findings were generally comparable to previous studies. One third of these patients received further consultation or neuroimaging because of incidental findings. In the evaluation of nonacute pediatric headache, overuse of neuroimaging leads to frequent discovery of incidental findings and increased testing. Individualized health care calls for physician-consumer discussions about current indications for neuroimaging, the general frequency of incidental findings, and potential difficulties in their interpretation.

Neuroimaging-use trends in nonacute pediatric headache before and after clinical practice parameters.

OBJECTIVES: The objective of this study was to determine trends in diagnostic neuroimaging-use rates in nonacute pediatric headache before and after publication of clinical practice guidelines. METHODS: Retrospective, cross-sectional analysis was conducted of neuroimaging rates for 725 children and adolescents who were aged 3 to 18 years with nonacute headache and normal neurologic examination and were evaluated in a single pediatric neurology clinic during study years 1992, 1996, 2000, and 2004. Following recommendations of current practice parameters, patients with conditions that justify consideration for neuroimaging (eg, progressive headache, abnormal neurologic examination) were excluded from this analysis. We recorded the origin of any neuroimaging request at the time of the clinic visit and any abnormal neuroimaging findings that led to major clinical consequences. RESULTS: Overall, the mean rate of neuroimaging for patients with nonacute headache was 45%. Use rates remained steady during the 13-year study period (range: 41%-47%). The majority of neuroimaging studies were ordered originally by primary care providers. The proportion of neuroimaging studies that were ordered by primary care providers increased significantly from 1992 to 2004. CONCLUSIONS: In the evaluation of patients who had nonacute pediatric headache and were referred to a child neurology clinic, neuroimaging-use rates remained stable during the past decade. An increasing proportion of neuroimaging studies are ordered by primary care providers. The influence of evidence-based medicine on medical decision-making may be partly responsible for curbing increases in neuroimaging overuse. The perceived value of neuroimaging by physicians and consumers deserves ongoing study.