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Background Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). Aberrant expression of transcription factor forkhead box P3 (FoxP3) has been suggested to underlie different immunological disorders as FOXP3 expression is essential for T regulatory cells (Tregs) to maintain their suppressive and anti-inflammatory functions and exert immunologic self-tolerance. Interleukin-35 (IL-35) is an important immunosuppressive cytokine that is produced mainly by CD4+ FOXP3+ Tregs. Objectives To assess the possible role of the FOXP3 rs3761548 (C/A) single-nucleotide variation (SNV) in relapsing-remitting multiple sclerosis (RRMS). Also, measurement of the serum IL-35 concentration and study its relation to different genotypes and the degree of disease-related disability. Methods A total of 100 RRMS patients and 90 healthy control subjects were subjected to genotyping for the FOXP3 (rs3761548) variant by TaqMan real-time PCR, and measurement of the IL-35 level in their sera by Elisa. Results The frequencies of the AA genotype and A allele were significantly higher in the MS patients than in the healthy controls (P = 0.008, OR = 2.53, 95% CI = 1.27–5.04; P = 0.001, OR = 1.98, 95% CI = 1.31–3.00, respectively). There was a significant association between FOXP3 rs3761548 variant and female MS patients. The serum IL-35 level was significantly higher in MS patients (1372 [575–2192] pg/mL) compared to healthy controls (604 [454–696] pg/mL) (P 0.0001). No significant differences were found between the different FOXP3 genotypes and EDSS score ( P = 0.730). Conclusion The FOXP3 rs3761548 gene variant may influence the genetic susceptibility to MS rather than affecting its course, severity or progression. The serum IL-35 level might have a role in the development of the disease, however its role in disease-related disability is questionable.

Background Given the diversity of multiple sclerosis (MS) symptoms including cognitive impairment in certain domains, the need to develop a rapid and at the same time thorough tool for cognitive assessment is mandatory and represents an unmet need in the clinical and research fields of MS. The Brief International Cognitive Assessment for MS (BICAMS) is a good and practical tool to achieve this mission but is not present in the Arabic language for Arabic speaking countries yet. Objectives To assess the reliability and validity of Arabic version of the BICAMS (Egyptian dialect). Methods Ninety Egyptian MS patients and 85 matched healthy controls underwent neuropsychological testing using the BICAMS Arabic version (Egyptian dialect) battery including the Symbol Digit Modality Test (SDMT), California Verbal Learning Test 2nd edition (CVLT-II), and revised Brief Visuospatial Retention Test- (BVRT-R). Test–retest data were obtained from MS patients 2 weeks after the initial assessment. Mean differences between both groups were assessed controlling for age, gender, and educational level. Results The MS patients scored significantly lower on the SDMT, CVLT-II, and BVMT-R tests compared to healthy controls (pr values of 0.85, 0.61, and 0.68, respectively. Conclusion BICAMS Arabic version is a reliable and valid tool for cognitive assessment of Arabic speaking MS patients in different clinical and research settings.

BackgroundMultiple sclerosis (MS) is a major cause of neurological disability in adults. Depression is one of the most common psychiatric comorbidities in MS patients with negative impact on patients’ quality of life. The aim of the study is to evaluate the role of diffusion tensor imaging (DTI) in monitoring the therapeutic response after high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) versus selective serotonin reuptake inhibitor (SSRI) therapy for relapsing remitting multiple sclerosis (RRMS) patients presenting with depression by measuring the factional anisotropy of the dorsolateral prefrontal cortex (DLPFC) before and after treatment and also to assess the treatments’ impact on patients’ cognitive functions and depression.ResultsFractional anisotropy (FA) only increased in rTMS group (0.44 ± 0.03 pre-rTMS vs 0.53 ± 0.05 post-rTMS,P< 0.001), but there were no significant changes in the SSRI group (0.44 ± 0.04 pre-SSRIs vs 0.45 ± .37 post-SSRIs,P= 0.072). Both rTMS and SSRI groups showed significant clinical improvement in Beck Depression Inventory (BDI) and Paced Auditory Serial Addition Test (PASAT) after either intervention (17.6 ± 3.25 pre-rTMS vs 10.6 ± 1.89 post-rTMS and 23 ± 6.36 pre-rTMS vs 24.87 ± 6.6 post-rTMS, respectively,P< 0.001; 17.67 ± 3.15 pre-SSRIs vs 0.6 ± 1.84 post-SSRIs and 23.8 ± 6.45 pre-SSRIs vs 25.07 ± 7.02 post-SSRIs, respectively,P< 0.001).ConclusionDTI is an ideal non-invasive tool for examining white matter integrity and can detect microstructural changes in the dorsolateral prefrontal cortex after rTMS and SSRI therapies for patients with MS and depression. FA increased only with rTMS denoting positive alteration in white matter microstructure. Both rTMS and SSRIs were equally effective in improving depression and cognition.

The ongoing coronavirus (COVID-19) pandemic is a global health emergency of international concern and has affected management plans of many autoimmune disorders. Immunosuppressive and immunomodulatory therapies are pivotal in the management of neuromyelitis optica spectrum disorder (NMOSD), potentially placing patients at an increased risk of contracting infections such as COVID-19. The optimal management strategy of NMOSD during the COVID-19 era remains unclear. Here, however, we examined the evidence of NMOSD disease-modifying therapies (DMTs) use during the present period and highlighted different scenarios including treatment of relapses as well as initiation and maintenance of DMTs in order to optimize care of NMOSD patients in the COVID-19 era.

Background Studies have shown that interferon-beta (IFN-β) treatment is associated with headaches in patients with multiple sclerosis (MS). Headaches can affect quality of life and overall function of patients with MS. We examined the frequency, relationships, patterns, and characteristics of headaches in response to IFN-β in patients with relapsing-remitting multiple sclerosis (RRMS). Patients and Methods This study was a prospective, longitudinal analysis with 1-year follow-up. The study comprised 796 patients with RRMS treated with IFN-β (mean age 30.84±8.98 years) at 5 tertiary referral center outpatient clinics in Egypt between January 2015 and December 2017. Headaches were diagnosed according to the International Classification of Headache Disorders ICHD-3 (beta version), and data were collected through an interviewer-administered Arabic-language-validated questionnaire with an addendum specifically designed to investigate the temporal relationship between commencement of interferon treatment, and headache onset and characteristics. Results Two hundred seventy-six patients had pre-existing headaches, and 356 experienced de novo headaches. Of 122 patients who experienced headaches before IFN-β treatment, 55 reported headaches that worsened following onset of IFN-β treatment. In patients with post-IFN-β headaches, 329 had headaches that persisted for >3 months, 51 had chronic headaches, and 278 had episodic headaches, and 216 of these patients required preventive therapies. Univariate analysis showed a >6- and an approximately 5-fold increased risk of headache among those treated with intramuscular (IM) INF-β-1a (OR 6.51; 95% CI: 3.73-10.01; P-value

In epilepsy, early diagnosis, accurate determination of epilepsy type, proper selection of anti-seizure treatment, and monitoring; all are essential. However, despite recent therapeutic advances and conceptual reconsiderations in the classification and management of epilepsy, serious gaps are still encountered in day-to-day practice in Egypt as well as several other limited resources countries. Premature mortality, poor quality of life, disabilities, diminished family function, cognitive problems, poor treatment outcomes, comorbidities, and significant economic burden are major challenges that impose urgent actions to be implemented at all levels. In recognition of this, a group of Egyptian epilepsy experts met through a series of consecutive meetings to specify main concepts and questions concerning the diagnosis, evaluation, and management of Epilepsy, with an ultimate goal of establishing a nationwide Egyptian consensus to guide health care professionals in the management of patients with epilepsy in general and to declare a pragmatic pathway for patients with drug-resistant epilepsy. The consensus was developed through a modified Delphi methodology. A thorough review of the most recent relevant literature and international guidelines was performed to evaluate their applicability to the Egyptian situation. Afterward, several remote and live rounds were scheduled to reach a final agreement for all listed statements. With the implementation of these unified recommendations, we believe this will bring about substantial improvements in both the quality of care and treatment outcomes for persons with epilepsy in Egypt.

BACKGROUND The safety of Ramadan fasting for Muslim patients suffering from multiple sclerosis (MS) is still a matter of debate. This work aimed to study the clinical course of MS during Ramadan fasting and to clarify the predictors of relapses and symptoms exacerbation. METHODS This retrospective study included 153 Muslim patients with MS. Data related to the disease course before Ramadan were obtained from patients' files, whereas data related to the disease activity during Ramadan, were collected from patients over the two months following Ramadan. RESULTS Patients with MS who experienced relapses, exacerbation of symptoms and development of new symptoms during Ramadan had a statistically significant longer disease duration compared to those who did not experience (P < 0.001

OBJECTIVE To study Ramadan's effect on migraine from the start to the end of the month and the tolerability of patients with migraine to fasting. BACKGROUND Fasting is a well-known trigger for migraine. Whether this effect on migraine is the same throughout the whole month, or whether it varies from the first to the last days of the month, has not been studied yet. METHODS A prospective cohort observational study was carried out on persons with migraine who fasted from 24 April to 23 May during Ramadan 2020. Each patient was asked to fill out their headache diary starting from Shaaban (the month before Ramadan) to the end of Ramadan. The Ramadan diary was divided by 10 days each, by which the patient was asked to accurately describe their migraine attacks in terms of frequency, duration, and intensity by using the Visual Analog Scale. Migraine attacks during the first day of fasting were assessed separately. RESULTS A total of 292 known persons with migraine from Egypt completed the study. Their median age was 33 years; 72/292 (24.7%) were male, and 220/292 (75.3%) were female. About 126/236 (53.4%) of the patients had migraine attacks on Ramadan's first day, most of them during fasting. The frequency of migraine attacks was significantly increased in Ramadan (median 4, interquartile range [IQR] 2-7) compared with Shaaban (median 3, IQR 1-6), p = 0.009. The number of attacks was significantly reduced in both the second (median 1, IQR 0-2.25) and the third 10 days of Ramadan (median 1, IQR 1-3) compared with the first 10 days (median 3, IQR 1-5) (p

Background and purpose The development of new biomarkers for multiple sclerosis (MS) is of paramount importance to improve our ability to predict disease progression and disability. The aim of this study was to evaluate the potential role of the optic nerve diameter (OND) measured by ultrasonography as a biomarker of early disability in patients with relapsing-remitting multiple sclerosis (RRMS). Methods Forty-nine RRMS patients, 23 with a history of optic neuritis (MS-ON) and 26 without a history of optic neuritis (MS N-ON), and 50 age- and sex-matched healthy control subjects were included in the study. The OND and optic nerve sheath diameter (ONSD) were measured by transorbital sonography (TOS), and the retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) thicknesses were measured by optical coherence tomography (OCT) using the Optovue RTVue™ system (Optovue, Inc., Fremont, CA, USA). Results There was no significant difference between the patient (whether ON or N-ON eyes) and control groups in either the OND (p=0.979) or the ONSD (p=0.911). However, patients with an expanded disability status scale (EDSS) score >2 had a significantly lower OND and RNFL thicknesses (p=0.014, p=0.010 respectively) than patients with an EDSS score ≤2. Statistical logistic regression revealed that OND was an independent predictor of EDSS>2 (p=0.044, OR =0.000, 95% CI=0.000-0.589). Conclusion The OND, as measured by ultrasonography, could be potentially used as a biomarker for the detection of early disability in RRMS patients.

Background Micro-RNAs (miRNAs) are evolving as biological markers for multiple sclerosis (MS) both in activity and remission. miR-96 is associated with remission, however, the exact mechanism through which it contributes to the anti-inflammatory pathway is not clear. Objective To study the expression of miR-96 and IL-10 (anti-inflammatory mediator) in relapsing remitting (RR) MS. Subjects and methods A case control study including 32 RRMS patients from Kasr Al-Ainy MS clinic, Cairo University, Egypt, and 26 healthy controls (HC). Assessment of serum IL-10 by ELISA, and miR-96 via real time PCR was done during relapse and remission in patients, and in HC. Results IL-10 was higher in RRMS patients during remission and in HC compared with relapse (P ˂ 0.001). miR-96 expression was higher in RRMS patients during remission compared with relapse and HC, and was higher in HC than in relapse (P ˂ 0.001). IL-10 level in remission correlated positively with disease duration (r = 0.41; P = 0.02). Otherwise, no correlation was found between IL-10 and relapse number or EDSS (P>0.05). miR-96 in relapse negatively correlated with EDSS in relapse (r=−0.47; P=0.007), but no correlation was found with disease duration or relapse number, whereas, miR-96 in remission did not correlate with any clinical parameters (P>0.05). No correlation was found between IL-10 and miR-96 either in relapse or remission (P>0.05). Conclusion IL-10 and miR-96 are associated with MS quiescence, however, the lack of a significant correlation between them implicates that the influence of miR-96 may be exhibited through some pathway other than IL-10.

During the current COVID-19 pandemic, many queries are raised regarding its nature, outcome, and sequelae. This letter raises the concern of potential impact on increasing the incidence of multiple sclerosis whose pathology involves a possible viral etiology. Besides, the potential neurotropism of the acute respiratory distress syndrome corona virus-2 (SARS-CoV-2), which is still not established, may raise concerns about the use of certain disease modifying therapies namely natalizumab.

Background In Egypt, the characterization of Neuromyelitis Optica Spectrum Disorder (NMOSD) is lacking. Objectives To determine the demographics, clinical features, aquaporin4 antibodies (AQP4-IgG) status, and neuroimaging of Egyptian NMOSD patients. Methods Retrospective analysis of 70 NMOSD patients’ records from the MS clinic, Kasr Alainy hospital, between January 2013 and June 2018. Results Patients’ mean age was 34.9 ± 9.2 years, and the mean at disease onset was 28.9 ± 10.5 years. Fifty-nine patients had an initial monosymptomatic presentation. AQP4-IgG was measured using either enzyme-linked immunosorbent assay (ELISA) (22 patients) or cell-based assay (CBA) (34 patients). Six and 29 patients had positive results, respectively (p < 0.001). 84% had typical NMOSD brain lesions. Longitudinally extensive myelitis was detected in 49 patients, and 9 had either short segments or normal cords. Treatment failure was higher in seropositive patients. Rituximab significantly reduced the annualized relapse rate (ARR) compared to Azathioprine with a percentage reduction of (76.47 ± 13.28) and (10.21 ± 96.07), respectively (p = 0.04). Age at disease onset was the only independent predictor for disability (p < 0.01). Conclusion Treatment failure was higher in seropositive patients. However, there was no difference in clinical or radiological parameters between seropositive and seronegative patients. Patients, who are polysymptomatic or with older age of onset, are predicted to have higher future disability regardless of the AQP4-IgG status.

The ongoing coronavirus (COVID-19) pandemic is a global health emergency of international concern and has affected management plans of many autoimmune disorders. Immunosuppressive and immunomodulatory therapies are pivotal in the management of neuromyelitis optica spectrum disorder (NMOSD), potentially placing patients at an increased risk of contracting infections such as COVID-19. The optimal management strategy of NMOSD during the COVID-19 era remains unclear. Here, however, we examined the evidence of NMOSD disease-modifying therapies (DMTs) use during the present period and highlighted different scenarios including treatment of relapses as well as initiation and maintenance of DMTs in order to optimize care of NMOSD patients in the COVID-19 era.

The emergence of the novel coronavirus disease 2019 (COVID-19) pandemic has become a major public health challenge of global concern since December 2019, when the virus was recognized in Wuhan, the capital city of Hubei province in China and epicenter of the COVID-19 epidemic. Given the novelty of COVID-19 and the lack of specific anti-virus therapies, the current management is essentially supportive. There is an absence of consensus on guidelines or treatment strategies for complex disorders such as multiple sclerosis (MS), in which the risk of infections is higher than in the general population. This is due to the overall impairment of the immune system typical of autoimmune diseases, in addition to accumulation of disabilities, and the iatrogenic effect generated by corticosteroids and the recommended disease-modifying therapies (DMTs). DMTs have different modes of action, but all modulate and interfere with the patient’s immune response, thereby raising concerns about adverse effects, such as an increased susceptibility to infections. In this review, we analyze the evidence for use of DMTs during the current critical period and ratify an algorithmic approach for management to optimize care between keeping DMTs, with their infection hazards, or coming off them, with the risk of disease activation. We also provide an algorithmic approach to the management of breakthrough activity during the COVID-19 pandemic.

Objective : This study aimed to report the severity of COVID-19 in a cohort of Egyptian patients with multiple sclerosis (MS) with particular attention on the impact of disease modifying drugs (DMDs). Methods and study population : We included 119 MS patients recruited from two centers, Ain-Shams university and Cairo university with confirmed or suspected COVID-19 during the period from May to September 2020 as a part of the MuSC-19 project. Univariate logistic regression was fitted to assess risk factors for severe COVID-19 (at least one outcome among hospitalization, ICU admission and death). Results : Females were 77%, mean age was 34 years, mean duration of MS was 5.28 years, median EDSS was 3, most of the patients (83%) had RRMS, while 15% and 2% had respectively SPMS and PPMS. Only eleven patients (9% of study population) had a severe outcome and 3 patients (3%) died. Headache was the only symptom significantly associated with the severity of COVID-19 (OR=10.85, P = 0.001). There was no association between any of the DMDs and severe COVID-19 outcome. Conclusion : This study showed an acceptable safety profile of DMDs in Egyptian MS patients who developed COVID-19, as 91% of the cohort had a favorable outcome. Headache as a symptom associated with severe outcome in Egyptian patients’ needs further validation.

Hatem S Shehata,1 Hadeer Mahmoud AbdelGhaffar,2 Mohammed Nasreldin,3 Alaa Elmazny,1 Ahmed Abdelalim,1 Asmaa Sabbah,1 Nevin M Shalaby1 1Department of Neurology, Cairo University, Giza, 2Department of Paediatrics, Fayoum University, Fayoum, 3Department of Psychiatrics, Cairo University, Giza, Egypt Introduction: Refractory epilepsy is a common clinical manifestation in patients with tuberous sclerosis complex (TSC), which can be complicated by many life-threatening conditions, such as status epilepticus (SE). However, very few reports mention the patterns and semiology of SE in those patients.Objective: To study the clinical characteristics and outcomes of SE in TSC patients.Materials and methods: This observational, prospective study was carried out on 36Egyptian children with definite TSC. Clinical history, general and neurological examination and psychometric evaluation by standard questionnaires were used to explore characteristics of epileptic manifestations and clinical patterns of SE. All included patients were required to have long-term video electroencephalograms (EEGs) and brain MRI performed.Results: A total of 32 attacks of SE were recorded in 21 patients (58.3%) in our cohort during a follow-up period of 2.8±1.1 years; of those patients, 15 had convulsive status, 7 had non-convulsive SE, 6 had refractory/super-refractory SE and 14 patients had a history of infantile spasms (epileptic spasms). The duration of status ranged from 40 to 150 min (mean ± standard deviation: 90±15). Fourteen patients with SE had severe mental retardation, 9 had autistic spectrum disorder and 22 had severe epileptogenic EEG findings. Patients with SE had higher tuber numbers (mean: 9.6), 5patients had subependymal giant cell astrocytomas and 2 patients had their SE after receiving everolimus.Conclusions: The incidence of SE in our patient sample is high (>50%); severe mental retardation, autistic features, history of infantile spasm (epileptic spasms) and high tuber burden are risk factors for developing SE. Keywords:Egyptian children, tuberous sclerosis, status epilepticus, infantile spasms, autistic spectrum

Naglaa A El-Sherbiny,1 Hatem Samir Shehata,2 Hanan Amer,2 Alaa Elmazny,2 Mohamed Masoud,1 Hanan Helmy,2 Nevin M Shalaby2 1Faculty of Medicine, Fayoum University, Faiyum, Egypt; 2Faculty of Medicine, Cairo University, Cairo, Egypt Background: The reported prevalence of headache disorders in Arab regions varies considerably between countries. This may be due to a lack of standardized survey instruments that capture the prevalence. Purpose of the study: Our goal was to construct and validate a structured headache questionnaire for Arabic-speaking headache patients to be used as an epidemiological survey instrument. Methods: We developed a culturally adapted interviewer-administered questionnaire in Arabic language comprising two sets of questions. The first set included personal and sociodemographic data together with a screening question regarding the presence of headaches over the last year. The second set was designed to define the type and pattern of headaches according to the International Classification of Headache Disorders criteria (for subjects with “yes” answers on the screening question). Validation process took place in two phases through probability random sampling selected from 1,221 headache subjects collected in an epidemiological survey 3 (n=70) and 6 months (n=232) later. A detailed assessment of patients’ headaches was performed by neurologists (blinded from the questionnaire diagnosis) who clinically assessed the patients’ headache. Results: The validity of the questionnaire was tested in 232 subjects with a mean age of 41.2±10.9 years, 72.8% of whom were females. The mean time to complete the questionnaire was 8.4±1.7 minutes. The intraclass correlation coefficient was 0.903 (95% confidence interval: 0.875–0.925), the Cronbach κ coefficient was 0.775 (95% confidence interval: 0.682–0.837), and the percentage of agreement was 84.5%.Conclusion: Our results support the use of this comprehensive questionnaire as a valid tool for headache assessment among Arabic-speaking patients. Keywords: Arabic, Egypt, headache, questionnaire, validation&nbsp

Background: Oral rehydration solution (ORS) is a form of oral rehydration therapy (ORT) for diarrhoea that has the potential to drastically reduce child mortality; yet, according to UNICEF estimates, less than half of children younger than 5 years with diarrhoea in low-income and middle-income countries (LMICs) received ORS in 2016. A variety of recommended home fluids (RHF) exist as alternative forms of ORT; however, it is unclear whether RHF prevent child mortality. Previous studies have shown considerable variation between countries in ORS and RHF use, but subnational variation is unknown. This study aims to produce high-resolution geospatial estimates of relative and absolute coverage of ORS, RHF, and ORT (use of either ORS or RHF) in LMICs. Methods: We used a Bayesian geostatistical model including 15 spatial covariates and data from 385 household surveys across 94 LMICs to estimate annual proportions of children younger than 5 years of age with diarrhoea who received ORS or RHF (or both) on continuous continent-wide surfaces in 2000-17, and aggregated results to policy-relevant administrative units. Additionally, we analysed geographical inequality in coverage across administrative units and estimated the number of diarrhoeal deaths averted by increased coverage over the study period. Uncertainty in the mean coverage estimates was calculated by taking 250 draws from the posterior joint distribution of the model and creating uncertainty intervals (UIs) with the 2·5th and 97·5th percentiles of those 250 draws. Findings: While ORS use among children with diarrhoea increased in some countries from 2000 to 2017, coverage remained below 50% in the majority (62·6%; 12 417 of 19 823) of second administrative-level units and an estimated 6 519 000 children (95% UI 5 254 000-7 733 000) with diarrhoea were not treated with any form of ORT in 2017. Increases in ORS use corresponded with declines in RHF in many locations, resulting in relatively constant overall ORT coverage from 2000 to 2017. Although ORS was uniformly distributed subnationally in some countries, within-country geographical inequalities persisted in others; 11 countries had at least a 50% difference in one of their units compared with the country mean. Increases in ORS use over time were correlated with declines in RHF use and in diarrhoeal mortality in many locations, and an estimated 52 230 diarrhoeal deaths (36 910-68 860) were averted by scaling up of ORS coverage between 2000 and 2017. Finally, we identified key subnational areas in Colombia, Nigeria, and Sudan as examples of where diarrhoeal mortality remains higher than average, while ORS coverage remains lower than average. Interpretation: To our knowledge, this study is the first to produce and map subnational estimates of ORS, RHF, and ORT coverage and attributable child diarrhoeal deaths across LMICs from 2000 to 2017, allowing for tracking progress over time. Our novel results, combined with detailed subnational estimates of diarrhoeal morbidity and mortality, can support subnational needs assessments aimed at furthering policy makers' understanding of within-country disparities. Over 50 years after the discovery that led to this simple, cheap, and life-saving therapy, large gains in reducing mortality could still be made by reducing geographical inequalities in ORS coverage. This work was primarily supported by a grant from the Bill & Melinda Gates Foundation (OPP1132415). L G Abreu has received support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Finance Code 001), Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Estado de Minas Gerais. O O Adetokunboh acknowledges the South African Department of Science and Innovation and the National Research Foundation. S M Aljunid acknowledges the Department of Health Policy and Management, Faculty of Public Health, Kuwait University and International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia for the approval and support to participate in this research project. H T Atalay acknowledges Aksum University. M Ausloos and C Herteliu are partially supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. P S Azzopardi was supported by an Australian National Health and Medical Research Council (NHMRC) early career fellowship. A Badawi is supported by the Public Health Agency of Canada. T W Bärnighausen was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research; the EU; the Wellcome Trust; and from National Institute of Child Health and Human Development of National Institutes of Health (NIH; R01-HD084233), National Institute on Aging of NIH (P01-AG041710), National Institute of Allergy and Infectious Diseases of NIH (R01-AI124389 and R01-AI112339), as well as Fogarty International Center of NIH (D43-TW009775). G B Britton is supported by Sistema Nacional de Investigación (SNI) de la Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT) of Panamá. A Barac is funded by the Project of Ministry of Education, Science and Technology of the Republic of Serbia (number III45005). D A Bennett was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the UK Department of Health and Social Care. V M Costa acknowledges her grant (SFRH/BHD/110001/2015), received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006. F Carvalho acknowledges UID/MULTI/04378/2019 and UID/QUI/50006/2019 support with funding from FCT/Ministério da Ciência, Tecnologia e Ensino Superior through national funds. K Deribe is supported by a Wellcome Trust grant (number 201900/Z/16/Z) as part of his International Intermediate Fellowship. C Herteliu is partially supported by a grant co-funded by European Fund for Regional Development through the Operational Program for Competitiveness (project ID P_40_382). P Hoogar thanks Centre for Bio Cultural Studies, Directorate of Research, Manipal Academy of Higher Education, Manipal and Centre for Holistic Development and Research, Kalaghatgi-Karnataka. S M S Islam is funded by a Fellowship from National Heart Foundation of Australia and Deakin University. M Jakovljevic and the Serbian part of this GBD contribution was co-funded through grant OI175014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. A P Kengne is supported by the South African Medical Research Council. Y J Kim's work was supported by the Research Management Centre, Xiamen University Malaysia, grants number XMUMRF/2018-C2/ITCM/0001. K Krishan is supported by a DST PURSE grant and UGC Center of Advanced Study awarded to the Department of Anthropology, Panjab University, Chandigarh, India. M Kumar acknowledges K43 TW010716-03. B Lacey acknowledges support from the NIHR Oxford Biomedical Research Centre and the British Heart Foundation Centre of Research Excellence, Oxford. P T N Memiah acknowledges the Council for the Development of Social Science Research in Africa. M Molokhia is supported by the NIHR Biomedical Research Center at Guy's and St Thomas' National Health Service Foundation Trust and King's College London. I Moreno Velásquez is supported by the Sistema Nacional de Investigación (SENACYT, Panamá). G C Patton is funded by an NHMRC Fellowship. A M Samy received a fellowship from the Egyptian Fulbright Mission programme. M M Santric-Milicevic acknowledges the support of the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract number 175087). A Sheikh acknowledges the support of Health Data Research UK. M R Sobhiyeh acknowledges the Clinical Research Development Center of Imam Reza Hospital, Kermanshah University of Medical Sciences for their wise advice. R Tabarés-Seisdedos was supported in part by grant PI17/00719 from Instituto de Salud Carlos III–FEDER. B Unnikrishnan acknowledges Manipal Academy of Higher Education, Manipal. M R Weaver was supported by the Bill & Melinda Gates Foundation grant OPP1127433. C S Wiysonge was supported by the South African Medical Research Council.

Background and purpose The development of new biomarkers for multiple sclerosis (MS) is of paramount importance to improve our ability to predict disease progression and disability. The aim of this study was to evaluate the potential role of the optic nerve diameter (OND) measured by ultrasonography as a biomarker of early disability in patients with relapsing-remitting multiple sclerosis (RRMS). Methods Forty-nine RRMS patients, 23 with a history of optic neuritis (MS-ON) and 26 without a history of optic neuritis (MS N-ON), and 50 age- and sex-matched healthy control subjects were included in the study. The OND and optic nerve sheath diameter (ONSD) were measured by transorbital sonography (TOS), and the retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) thicknesses were measured by optical coherence tomography (OCT) using the Optovue RTVue™ system (Optovue, Inc., Fremont, CA, USA). Results There was no significant difference between the patient (whether ON or N-ON eyes) and control groups in either the OND (p=0.979) or the ONSD (p=0.911). However, patients with an expanded disability status scale (EDSS) score >2 had a significantly lower OND and RNFL thicknesses (p=0.014, p=0.010 respectively) than patients with an EDSS score ≤2. Statistical logistic regression revealed that OND was an independent predictor of EDSS>2 (p=0.044, OR =0.000, 95% CI=0.000–0.589). Conclusion The OND, as measured by ultrasonography, could be potentially used as a biomarker for the detection of early disability in RRMS patients.

Background Chronic migraine is a prevalent disabling disease, with major health-related burden and poor quality of life. Long-term use of preventive medications carries risk of side effects. Objectives The aim of this study was to compare repetitive transcranial magnetic stimulation (rTMS) to botulinum toxin-A (BTX-A) injection as preventive therapies for chronic migraine. Methods A pilot, randomized study was conducted on a small-scale sample of 29 Egyptian patients with chronic migraine, recruited from Kasr Al-Aini teaching hospital outpatient clinic and diagnosed according to ICHD-III (beta version). Patients were randomly assigned into two groups; 15 patients received BTX-A injection following the Phase III Research Evaluating Migraine Prophylaxis Therapy injection paradigm and 14 patients were subjected to 12 rTMS sessions delivered at high frequency (10 Hz) over the left motor cortex (MC, M1). All the patients were requested to have their 1-month headache calendar, and they were subjected to a baseline 25-item (beta version) Henry Ford Hospital Headache Disability Inventory (HDI), Headache Impact Test (HIT-6), and visual analogue scale assessment of headache intensity. The primary efficacy measures were headache frequency and severity; secondary measures were 25-item HDI, HIT-6, and number of acute medications. Follow-up visits were scheduled at weeks 4, 6, 8, 10, and 12 after baseline visit. Results A reduction in all outcome measures was achieved in both the groups. However, this improvement was more sustained in the BTX-A group, and both the therapies were well tolerated. Conclusion BTX-A injection and rTMS have favorable efficacy and safety profiles in chronic migraineurs. rTMS is of comparable efficacy to BTX-A injection in chronic migraine therapy, but with less sustained effect.

Corticobasal syndrome (CBS) is a sporadic tauopathy that manifests by a various combination of motor and cognitive deficits, which makes its diagnosis challenging. Treatment of CBS is symptomatic and based on evidence from other similar disorders due to the lack of studies on CBS. The aim of the study was to investigate low-frequency repetitive transcranial magnetic stimulation (rTMS) as a therapeutic tool in CBS. Twenty-six patients with clinically evident CBS according to Cambridge criteria were followed for 12–18 months while receiving low-frequency rTMS combined with pharmacological, rehabilitation treatment and botulinum toxin injection. The majority of patients are manifested with akinetic-rigid syndrome and cognitive dysfunction. There was improvement of the UPDRS and quality of life after 3 months of therapeutic interventions (P

Sherif M Hamdy,1 Maged Abdel-Naseer,1 Nevin M Shalaby,1 Alaa Elmazny,1 Marian Girgis,2 Mona A Nada,1 Amr Hassan,1 Husam S Mourad,1 Mohamed I Hegazy,1 Ahmed Abdelalim,1 Nirmeen A Kishk,1 Noha T Abokrysha,1 Shaimaa A Genedy,1 Ehab A Essawy,3 Hatem S Shehata1 1Neurology Department, Cairo University, Cairo, Egypt; 2Pediatric Department, Cairo University, Cairo, Egypt; 3Division of Biochemistry, Chemistry Department, Faculty of Science, Helwan University, Helwan, Egypt Introduction: Although the frequency of pediatric-onset multiple sclerosis (POMS) has increased in recent decades, it is still highly uncommon, which creates a need for the involvement of more registries from various clinical centers.Objective: To characterize the demographic, clinical, and paraclinical features of Egyptian patients with POMS.Patients and methods: A retrospective chart review study was undertaken on 237 Egyptian patients with demyelinating events which started before the age of 18 years who attended one of five tertiary referral centers in Cairo, Egypt.Results: Multiple sclerosis was diagnosed in 186 patients, 47 (25.27%) patients had disease onset before the age of 12 years; “early-onset pediatric multiple sclerosis (EOPMS)”. The mean age of disease onset was (14.13±2.49years), with a female:male ratio of 1.62:1, none of the enrolled patients had a primary progressive course (PPMS), whereas 10 patients (5.38%) had a secondary progressive form. Approximately two-thirds of the patients had monofocal disease onset, and less than 10% presented with encephalopathy; most of them had EOPMS. Motor weakness was the presenting symptom in half of the patients, whereas cerebellar presentation was detected in 34.95%, mainly in EOPMS. Seizures (not related to encephalopathy) were more frequent in those with EOPMS. Initial brain magnetic resonance images were positive in all patients, with detected atypical lesions in 29.03%, enhanced lesions in 35.48%, black holes in 13.98%, and infratentorial in 34.41%. Cervical cord involvement was found in 68.28%. More than two-thirds of the patients received either immunomodulatory or immunosuppressant (IS) treatment throughout their disease course, and about half of them received their treatment within the first year from symptoms onset, with a more favorable outcome, and patients with highly active disease received natalizumab, fingolimod, or other IS.Conclusion: The results from this registry – the largest for MS in the Arab region to date – are comparable to other registries. Immunomodulatory therapies in POMS are well tolerated and efficacious and they can improve the long-term outcome in children. Keywords: multiple sclerosis, pediatric onset, early onset, registry, Egypt&nbsp

Sherif M Hamdy,1 Maged Abdel-Naseer,1 Nevin M Shalaby,1 Alaa N Elmazny,1 Ahmed A Nemr,2 Amr Hassan,1 Mohamed I Hegazy,1 Husam S Mourad,1 Nirmeen A Kishk,1 Mona A Nada,1 Ahmed Abdelalim,1 Amr M Fouad,1 Hatem S Shehata1 1Neurology Department, Cairo University, 2Neurology Department, Maadi Military Hospital, Cairo, Egypt Background: Multiple sclerosis (MS) is a complex autoimmune disease with a heterogeneous presentation and diverse disease course. Recent studies indicate a rising prevalence of MS in the Middle East.Objective: To characterize the demographics and disease features of Egyptian patients attending four tertiary referral MS centers in Cairo.Materials and methods: This was a retrospective, observational study on 1,581 patients between 2001 and 2015. Medical records were reviewed and data were identified and extracted in a standardized electronic registry.Results: The mean age of disease onset was 26.6±7.8 years, with the majority being female (2.11:1). Relapsing–remitting MS was the most common type (75.1%). The main presenting symptom was motor weakness (43.9%), which was also the most frequent symptom during the disease course. Family history of MS was found in 2.28%. Higher initial Expanded Disability Status Scale score, black holes, and infratentorial lesions on initial magnetic resonance imaging were independent factors for disease progression by univariate analysis (OR 3.87 [95% CI 1.84–6.51], 4.14 [95% CI 3.08–5.58], 4.07 [95% CI 3.21–4.99], respectively); however, in multivariate analysis, only infratentorial lesions were an independent risk for disease progression (OR 6, 95% CI 2.99–12.02; P=0.0005).Conclusion: The results from this registry – the largest for MS in the Arab region to date – are comparable to other registries with slight differences. Keywords: multiple sclerosis, MS registry, epidemiology, Middle East, North Africa, Egypt&nbsp

Background Cytokines are major contributors in the immune disruption in multiple sclerosis (MS). Objective Evaluating the proinflammatory (IL-17A) and anti-inflammatory (IL-10) cytokines in relapsing-remitting (RR) MS patients at time of relapse and during remission. Subjects and method A case-control study including 30 RRMS patients and 15 controls. Patients were recruited from the Kasr Al-Ainy MS research unit (KAMSU), Cairo University, Egypt. Levels of IL-17A and IL-10 were assessed in patients' sera, during relapse and 30 days after IV methylprednisolone, and in control subjects using enzyme linked immunosorbent assays (ELISA). Results IL-17 was higher in patients during relapse and remission phases when compared with controls (P = 0.001), whereas, IL-10 was higher in patients during remission but normal during relapse (P = 0.01; 0.86 respectively). IL-17 increased during relapses (P = 0.001) while IL-10 increased during remissions (P = 0.028). No significant correlations were found between both interleukins and age at onset; disease duration, number of relapses; or EDSS. Conclusion RRMS patients can have a regulatory imbalance between both pro-and antiinflammatory cytokines, which could be a target for treatment strategies rather than focusing on a single cytokine.

Background There is abundance of epidemiological studies of headache in developed and western countries; however, data in developing countries and in Egypt are still lacking. This study aims to detect the prevalence of primary headache disorders in both urban and rural sectors in Fayoum governorate, Egypt. Methods A total of 2600 subjects were included using multi-stage stratified systematic random sampling, with respondent rate of 91.3 %. A pre-designed Arabic version, interviewer-administered, pilot tested structured questionnaire was developed according to The International Classification of Headache Disorders, 3rd edition (beta version), and this questionnaire was validated and the strength of agreement in headache diagnosis was good. Results The 1-year headache prevalence was 51.4 %, which was more prevalent in urban dwellers. The most common primary headache type was episodic tension type headache (prevalence; 24.5 %), followed by episodic migraine (prevalence; 17.3 %), both types peaked in midlife. Headache disorders were more common in females with exception of cluster headache that showed the expected male dominance. The risk of chronic headache increased more than one fold and half when the participants were females, married, and in those with high education. More than 60 % of our participants did not seek medical advice for their headaches problem; this percentage was higher in rural areas. Conclusions Primary headache disorders are common in Egypt; prevalence rate was comparable with western countries with exception of episodic tension headache. Still headache is under-estimated and under-recognized in Egypt and this problem should be targeted by health care providers.

Background Stroke is a major cause of mortality and morbidity worldwide. Poor knowledge of stroke risk factors, symptoms and appropriate response to stroke are possible causes of poor outcome. Objective The aim of this study was to evaluate the knowledge and attitude towards different aspects of stroke in a sample of Cairo University Hospitals' workers. Patients and methods A structured self-administered questionnaire was administered by 111 workers who were classified into clinical workers (physicians, house officers, nurses, laboratory technician and pharmacists) and nonclinical workers (administrative, sanitary and security workers). Results Out of 111 participants, 92 completed the questionnaire. Most participants had heard of stroke (91.3%), mostly through encountering a family member with a stroke rather than through mass media (10.9%). Hypertension was the most common identified stroke risk factor (66.3%). Clinical workers were more likely to identify risk factors. The most common identified stroke symptoms were slurring of speech (38.5%) and elevated blood pressure (38.5%). Clinical workers were more likely to identify symptoms such as slurring of speech (P = 0.042) and altered state of consciousness (P Conclusion Knowledge and perception of stroke in Cairo University Hospitals' workers appear to be poor, especially among nonclinical workers. Planning educational programs for raising the level of knowledge and awareness of stroke, both on the level of hospital workers and on the public level, is important to improve stroke management and outcome.

Background Multiple sclerosis (MS) is the quintessential neurologic disorder from which one can gain insights into the principles of afferent and efferent neuro-ophthalmology. The popularity of eye movements as an experimental tool can be partly attributed to the fact that they can be conveniently and accurately measured and analyzed, and also because much is known about their neural substrate. It is therefore no surprise that eye movements have been commonly applied to better understand the visual and motor disorders in patients with MS. Objectives The aim of this study was to demonstrate the vast ocular motor abnormalities that occur in this disease using videonystagmography as our tool of description and determine the relationship with Expanded Disability Status Scale (EDSS) and MRI findings. Materials and methods The current study included 76 patients who were divided into two groups. Group I comprised 54 patients with relapsing-remitting multiple sclerosis who fulfilled the Revised Mcdonald's criteria for diagnosis of MS. The age of the patients in group I ranged from 20 to 68 years, with a mean of 35.13 ± 9.42 SD (23 men and 31 women). Group II comprised 22 healthy age-matched and sex-matched individuals who were recruited from the general population and were not relatives of the patients. Their ages ranged from 19 to 54 years, with a mean of 33.81 years ± 10.07 SD (11 men and 11 women). Video-nystagmography, saccadic tracking, random horizontal saccades, optokinetic tracking (at 20, 40, and 60΀/s), smooth pursuit (0.2, 0.3, 0.4, 0.5, 0.6, and 0.7 Hz), and gaze-evoked nystagmus were examined in both groups. Group I, in addition, was subjected to a thorough neurological history and neurological examination, EDSS assessment, ophthalmologic examination (visual acuity and ocular motility), and radiological assessment by MRI with and without contrast. Results The eye movement disorders most commonly noted are saccadic dysmetria, followed by gaze-evoked nystagmus and pendular nystagmus. They are caused by disease affecting the brain stem and cerebellar circuits. Reduced pursuit gain and saccadic pursuit were also noted. A strong correlation between brainstem and cerebellar MRI lesions and the affection of the ocular motor system was well noted. A high EDSS score was well correlated with abnormal ocular motor test findings. Conclusion Ocular motor system tests are more sensitive than conventional clinical examinations in identifying abnormalities in MS.

WCN 2013 No: 382 Topic: 2 — Movement Disorders Long-term complications of Parkinson's disease — 15th year, 20th year, and beyond; A hospital-based observational study H. Shibayama, S. Kaji, D. Nishida, S. Hirata, F. Katada, S. Sato, T. Fukutake. Neurology, Kameda Medical Center, Kamogawa, Japan Background: Long-term complications of Parkinson's disease (PD) based on regular follow-up in a local neurological center is insufficiently appreciated. Patients and methods: From registered PD patients, we selected those who have been examined in 15th and/or 20th year of the disease (YD) and information about motor status, levodopa equivalent daily dosage (LEDD), hallucination, cognitive disturbance, and dysphagia in each year was collected. Results: Of all PD patients between April 1995 and December 2012 (n = 538, male/female 222/316), 72 patients (13.4%) were examined in their 15th YD (Group PD ≥ 15; age at onset (AO) 58.1 ± 8.1 yearold; modified Hoehn and Yahr stage (mHY) at on/off, 3.3 ± 0.9/3.9 ± 0.9; LEDD 567 ± 239 mg/day) and only 18 patients (3.3%) have taken their 20th YD examination (Group PD ≥ 20; AO 53.4 ± 6.6, mHY at on/off, 3.8 ± 0.9/4.4 ± 0.7; LEDD 703 ± 208 mg/day). Groups PD ≧ 15 and PD ≥ 20 have significantly younger AO (p = 0.0001, p b 0.0001) than patients who have less than 15th YD history (PD b 15, n = 466, AO 67.4 ± 8.8). In Group PD ≥ 15/PD ≥ 20, troublesome hallucination (mainly visual, n = 36/13, 50.0/72.2%) appeared in 15.1 ± 2.8/17.7 ± 2.6th year, cognitive disturbance (n= 27/10, 37.5/55.6%) in 16.0 ± 2.9/18.0 ± 2.5th year, and dysphagia (n= 29/ 13, 40.3/72.2%) in 18.1 ± 3.4/21.0 ± 2.3th year. Follow-up periods after appearance of hallucination, cognitive disturbance, and dysphagia in Group PD ≧ 15 are 4.2 ± 2.7, 3.2 ± 2.6, 1.7 ± 2.1 years, respectively. The longest treated patient had AO at 54 year-old and was in mHY 3/0/ 4.0 in 29th YD without these 3 complications. Conclusions: During long-term treatment of PD, hallucination, cognitive disturbance and swallowing problem appear in near half ormore of the patients after 15th YD and seem to contribute to lost follow-up. doi:10.1016/j.jns.2013.07.424 Abstract — WCN 2013 No: 995 Topic: 2 — Movement Disorders Role of magnetic resonance spectroscopy in differentiating parkinsonian syndromes of various etiologies WCN 2013 No: 995 Topic: 2 — Movement Disorders Role of magnetic resonance spectroscopy in differentiating parkinsonian syndromes of various etiologies I. El-Banhawy, M. El-Toukhy, I. Fahmy, N.M. Shalaby, M.A. Nada, H.S. Shehata, I. Ismaiel. Neurology, Cairo University, Cairo, Egypt; Radiology, Cairo University, Cairo, Egypt Background: Parkinsonism is not a single disease entity as it has a number of causes that differ in the pathology according to the affected brain region. To our knowledge, no previous studies have beenpublished to investigate the role of magnetic resonance spectroscopy (MRS) in the differentiation between idiopathic Parkinson's disease (IPD), druginduced parkinsonism (DIP) and Wilson's disease (WD). Objective: Investigating the role of MRS in the differentiation between various parkinsonian syndromes. Subjects & methods: The study was conducted on 40 parkinsonian patients: 27 patients with IPD, 6 patients with DIP, and 7 patients with WD, and 15 normal control subjects. All were examined using single voxel protonMRS study of striatum, frontal cortex and subcortical white matter. Measured MRS parameters were N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine–phosphocreatine (Cr) and with peak area ratios (NAA/Cr, Cho/Cr, NAA/Cho ratios). Results: Patients with parkinsonism had significantly more cortical Cr and less NAA/Cr ratio and more subcortical NAA, Cr, Cho, and Cho/Cr ratios compared to control subjects. DIP patients showed significantly lower striatal Cho/Cr ratio and significantly higher subcortical Cho/Cr ratio compared to IPD. While comparing WD and IPD patients, a significantly lower cortical Cho/Cr ratio and significantly higher subcortical NAA/Cr and cortical NAA/Cho ratios were found inWD. Patients withWD had significantly higher cortical and subcortical NAA/Cho and striatal NAA/Cr ratios compared to DIP patients. Conclusion: MRS can be used as a useful in vivo investigative tool in differentiating between parkinsonian syndromes of various etiologies. doi:10.1016/j.jns.2013.07.425 Abstract — WCN 2013 No: 203 Topic: 2 — Movement Disorders A long-term, open-label study of levodopa–carbidopa intestinal gel in advanced Parkinson's disease patients: safety and motor-symptom endpoints WCN 2013 No: 203 Topic: 2 — Movement Disorders A long-term, open-label study of levodopa–carbidopa intestinal gel in advanced Parkinson's disease patients: safety and motor-symptom endpoints A.J. Espay, P. Odin, H.H. Fernandez, R.A. Hauser, D.G. Standaert, A.E. Lang, V.S. Fung, F. Klostermann, W.Z. Robieson, K. Chatamra, J. Benesh. University of Cincinnati Academic Health Center, Cincinnati, OH, USA; Klinikum-Bremerhaven, Bremerhaven, Germany; Skane University Hospital, Lund, Sweden; Cleveland Clinic, Cleveland, OH, USA; University of South Florida, Tampa, FL, USA; University of Alabama at Birmingham, Birmingham, AL, USA; University of Toronto, Toronto, ON, Canada; Westmead Hospital and Sydney Medical School, Sydney, NSW, Australia; Charite-University Medicine Berlin, Berlin, Germany; AbbVie Inc., North Chicago, IL, USA Background: Motor complications in Parkinson's disease (PD) are associated with pulsatile dopaminergic stimulation. Levodopa– carbidopa intestinal gel (LCIG) provides continuous drug infusion via an intrajejunal percutaneous gastrostomy tube. Objective: To present safety and efficacy results of an international, 54-week, open-label study of LCIG in patients with advanced PD. Patients and methods: PD patients experiencing severe motor fluctuations (≥3 h/d OFF-time) despite optimized medical therapy were enrolled. Individualized LCIG dosingwas permitted up to 16 h/d; other PD medications were allowed after 28 days. Efficacy outcomes included OFF-time, ON-time withand ON-time without troublesome dyskinesias (TSD) (patient-diary-assessed), and UPDRS. AEs were monitored. Results: 272 (76.8%) of 354 patients completed the study. Mean (SD) exposure to LCIG was 328.5 (132.3) days. Mean [SD] OFF-time (baseline = 6.8[2.4] h/d, endpoint = 2.3[2.1], P b .001) and ON-time with TSD (baseline = 1.6[2.0], endpoint = 1.2[2.1], P= .002) were reduced, while ON-time without TSD (baseline = 7.6[2.5], endpoint = 12.4[2.6], P b .001) was increased. UPDRS scores were improved (Part II: change at endpoint = -4.4[6.5]; Part III: change=−7.4[13.2]; P b .001 both). Mean total daily dose of levodopa (mg) was steady (Week 4= 1613.7; Endpoint = 1620.9). Ninety subjects (27.8%) took only LCIG; 158 (48.8%) took only concomitant oral levodopa formulations. While AEs occurred in 323 (91.2%) patients, most weremild ormoderate and transient, and only 27 (7.6%)withdrewdue to an AE. Complication of device insertion (34.9%) and abdominal pain (31.2%) wasmost common. Conclusion: In this large, long-term, prospective study, LCIG provided advanced PD patients with significant and clinically meaningful improvements in motor function and acceptable safety. Support: AbbVie. doi:10.1016/j.jns.2013.07.426 Abstracts / Journal of the Neurological Sciences 333 (2013) e109–e151 e127

Background Botulinum toxin type A (BTX-A) has been reported to have analgesic effects independent of its action on muscle tone, mostly by acting on neurogenic inflammatory mediators and controlling the neurotransmitter release of sensory and autonomic nerve terminals that are involved in many chronic painful conditions as chronic intractable trigeminal neuralgia (TN). The aim of our work was evaluating the efficacy, safety, and tolerability of BTX-A for the treatment of intractable idiopathic TN. Methods This was a randomized, single-blinded, placebo-control study carried out on 20 Egyptian patients with intractable TN. Patients received a one-time subcutaneous administration of BTX-A using “follow the pain” method. The primary efficacy measure was reduction in pain severity on the 10-cm VAS score as well as in paroxysms frequency from the baseline to week 12 (endpoint last observation carried forward [LOCF]). Secondary efficacy measures included QoL assessment and number of acute medications received from baseline to the endpoint. Results Pain reduction at the 12-week endpoint was significant in BTX-A group (p