A. Ahmed

A novel nonsense mutation in DNAJC6 expands the phenotype of autosomal recessive juvenile‐onset Parkinson disease

We appreciate Dr. Jiang’s and Liu’s interest in our recent study, where we reported that the minor allele of a missense variant (rs3796529) in the REST gene may be protective for rate of hippocampal volume loss in individuals with mild cognitive impairment (MCI) with APOE E3/E3 genotype. In their letter, the authors reported that rs3796529 was not significantly associated with the volumes of 7 subcortical regions of human brain determined by magnetic resonance imaging using data from the large-scale genome-wide association study (GWAS) summary statistics from the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium. The authors’ negative findings in contrast to the association we reported may be due to numerous differences, including the following factors. First, the ENIGMA consortium included patients diagnosed with anxiety, Alzheimer disease (AD), epilepsy, major depressive disorder, or schizophrenia (>20% of the discovery participants). Although the presence of any diagnosis was used as a covariate in ENIGMA, various neurologic and psychiatric disorders may have differential effects on brain structure volumes, and this may have averaged out any influence of the REST variant. In contrast, the discovery samples in our study included only individuals with MCI, often representing a prodromal stage of AD. Second, the participants of the ENIGMA consortium were aged 9 to 97 years, covering most of the human lifespan, whereas the participants in our study were older adults (mean age 5 74.4 years, range 5 57.8–85.7 years). Finally, it should be noted that our sample included only participants with APOE E3/E3 genotype, as it was designed to identify variants independent of the well-established APOE E4 AD risk factor. In contrast, Dr. Jiang and Liu examined GWAS summary statistics obtained using all ENIGMA samples regardless of APOE E4 genotype. We believe Dr. Jiang’s and Liu’s negative findings are interesting yet should be interpreted with caution given the marked differences in sample characteristics and study design from the Alzheimer’s Disease Neuroimaging Initiative report that addressed a very specific older adult population. The large sample size in ENIGMA should not dissuade further studies, which we believe are warranted to more precisely characterize the association of this and other REST variants with subcortical brain structure volumes in cognitively normal older adults as well as those with neurodegenerative disorders.

Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan

Hereditary spastic paraplegias (HSP) are the second most common type of motor neuron disease recognized worldwide. We investigated a total of 25 consanguineous families from Sudan. We used next-generation sequencing to screen 74 HSP-related genes in 23 families. Linkage analysis and candidate gene sequencing was performed in two other families. We established a genetic diagnosis in six families with autosomal recessive HSP (SPG11 in three families and TFG/SPG57, SACS and ALS2 in one family each). A heterozygous mutation in a gene involved in an autosomal dominant HSP (ATL1/SPG3A) was also identified in one additional family. Six out of seven identified variants were novel. The c.64C>T (p.(Arg22Trp)) TFG/SPG57 variant (PB1 domain) is the second identified that underlies HSP, and we demonstrated its impact on TFG oligomerization in vitro. Patients did not present with visual impairment as observed in a previously reported SPG57 family (c.316C>T (p.(Arg106Cys)) in coiled-coil domain), suggesting unique contributions of the PB1 and coiled-coil domains in TFG complex formation/function and a possible phenotype correlation to variant location. Some families manifested marked phenotypic variations implying the possibility of modifier factors complicated by high inbreeding. Finally, additional genetic heterogeneity is expected in HSP Sudanese families. The remaining families might unravel new genes or uncommon modes of inheritance.

Prevalence of epilepsy in 74,949 school children in Khartoum State, Sudan

Abstract Background: Data on childhood epilepsy in Sudan are scarce and the only published study on its prevalence was published in 1983. This study aimed to determine the current prevalence of epilepsy in school children in Khartoum State. Methods: This is an analytical population-based, cross-sectional study conducted in Khartoum State, Sudan. The study included students in the basic (primary) schools aged 6–14 years. Simple random sampling was used to draw a cluster of four of the seven localities comprising Khartoum State. The sample frame consisted of 1609 public schools (808,624 pupils) and 787 private schools (194,613 pupils), a total of 2396 schools (1,003,237 pupils). A sample size of 75 940 pupils was estimated and 250 schools were drawn from a sample frame of 2396 schools using a stratified random sampling technique. Consent was obtained from the headmaster/head teacher of the selected schools who arranged a meeting with the tutor/teacher responsible for each class. The study team asked whether any of the pupils was ever noticed or known to have had any kind of seizures, and a confidential letter was sent to the parents of each identified pupil. The letter included an explanation of the aims of the study, information on the research group and the kind of help the research group could offer; contact numbers and email addresses were made available if they wished to participate in this study. Those who consented to participate were then given an appointment at the Epilepsy Outpatient Department, Gaafar Ibnauf Children’s Hospital, Khartoum where they were evaluated by the paediatric neurologist. Results: Altogether, 74,949 pupils were enrolled for the study, 398 of whom were identified initially as having seizures and 332 of whom (83.4%) were identified by a paediatric neurologist. Of the 332, 303 (91.3%) proved to have epileptic seizures, 250 (82.5%) were known to have epilepsy, and 53 (17.5%) were newly diagnosed during the survey. The male to female ratio was 1.5:1. The total prevalence of epilepsy in Khartoum State was estimated to be 4/1000. The highest prevalence was in Jabal Awliya Locality (4.87/1000) and the lowest was in Khartoum Locality (3.35/1000). Twenty-nine (8.7%) patients proved to have non-epileptic seizures. The majority (15, 51.6%) had psychogenic non-epileptic seizures, and four (13.6%) had syncope. The majority (171, 56.43%) of patients had generalised epilepsy, 109 (35.97%) had focal epilepsy, and 23 (7.6%) had unclassified epilepsy. Conclusion: The prevalence of epilepsy in school children in Khartoum State (4/1000) is higher than that reported previously from Khartoum Province in 1983 (0.9/1000).

S134. A comparative study of sensory nerve conduction velocity between right handed and left handed subjects

Introduction Motor Nerve conduction study is one of the electrophysiological tests performed to evaluate electrical conduction of motor nerves. Many studies involved nerve conduction velocity of peripheral nerves, but only few addressed this issue in relation to handedness with lots of controversies in their results. This Study was conducted to compare motor nerve conduction velocity between right-handed and left-handed subjects in large sample size. Methods The study was carried as analytical cross-sectional study at the department of physiology, Faculty of Medicine, University of Khartoum and involved 120 healthy students from the medical campus, of whom 60 were right-handed and 60 were left-handed. Nerve conduction studies were performed using Medelec-Synergy machine. Two peripheral motor nerves of the upper limb (Median & Ulnar nerves) were investigated in each subject of the two groups bilaterally. Results The study revealed no significant difference in motor nerve conduction velocities of the investigated motor nerves (right-median, left-Median, right-ulnar & left-ulnar nerves) between the right-handed and the left-handed groups (P value > 0.05). Also when testing each group separately, no significant difference was found in motor nerve conduction velocities of the motor nerves (median, ulnar) between the right and left sides of the same subject, (P value > 0.05). Conclusion The study concluded that there is no significant difference in nerve conduction velocity between right-handed and left-handed subjects. Same finding was found between right and left sides of the same subject, in both right-handed and left-handed groups. This proved that nerve conduction velocity has no relation with handedness.

S40. Acute and subacute motor neuropathy in type II diabetic patients

Introduction Diabetic neuropathy is the most common complication of diabetes mellitus (DM), affecting as many as 50% of patients with type 1 and type 2 DM. There are four main types of diabetic neuropathy; Peripheral neuropathy, autonomic neuropathy, radiculo-plexus neuropathy (diabetic-amyotrophy) and mononeuropathy. The aim of the study was to describe the clinical presentation, electrophysiological investigations and in the future the immunological profile of such patients. Methods Seven type II diabetic patients were selected for the study. Ethical approval and patients’ informed consent have been obtained. They are all presented with acute and subacute onset of predominantly lower limb distal muscle weakness, on occasion proximal. The onset of this weakness was not preceded by upper respiratory tract infection, diarrhea or febrile illness. Results On examination there was symmetrical weakness of the distal foot flexors and extensors (power ranges 0–3), lower limb reflexes varies from diminished to absent. Tone was normal in the majority and flaccid in some of the patients. All modalities of sensation are intact except for disturbance of light touch in two patients. All patients were investigated for other causes of neuropathies. Neurophysiological investigations revealed signs of predominant demyelination with axonal degeneration. Patients showed very good response to immunoglobulin infusion (i.e. recovery of weakness after one to three months). Immunological studies are undergoing. Conclusion This was a preliminary report of a very uncommon presentation of acute motor neuropathy in diabetic patients. The cause possibly might be immune-mediated nerve damage but this has to be confirmed when we recruit more patients with detailed immune-profile studies.