Hatem S Shehata

Botulinum toxin-type A: could it be an effective treatment option in intractable trigeminal neuralgia?

BackgroundBotulinum 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.MethodsThis 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.ResultsPain reduction at the 12-week endpoint was significant in BTX-A group (p<0.0001); VAS scores at endpoint LOCF relative to baseline for BTX-A group showed a decrease of 6.5 compared with a decrease of 0.3 for placebo, also there was a significant decrease in the number of acute medications and an increase in QoL functioning scale.ConclusionThese results indicate that BTX-A has a direct analgesic effect in patients with TN and can represent a therapeutic option for intractable cases.

Repetitive transcranial magnetic stimulation versus botulinum toxin injection in chronic migraine prophylaxis: a pilot randomized trial

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.

Oromandibular dystonia in Yemeni patients with khat chewing: a response to botulinum toxin treatment

Khat-(Catha edulis)related oromandibular dystonia is a difficult-to-treat subset of movement disorders that involve masticatory muscles with diverse and incapacitating manifestations. The aim of this study was to evaluate the efficacy of Botulinum toxin-type A therapy in khat chewer Yemeni patients with oromandibular dystonia. This prospective study included 18 khat-chewers Yemeni patients with refractory oromandibular dystonia, who were subjected to Botulinum toxin-A injection and followed up for 3 months thereafter. Primary efficacy outcome was the global impression scale, and secondary outcome measure was the Unified Dystonia Rating Scale. Patients showed improvement of both efficacy measures, maximum satisfactory responses were detected at the forth week after injection. No major adverse events were detected. Botulinum toxin-A is considered an effective and safe treatment option for refractory oromandibular dystonia in khat-chewers

Clinical patterns and outcomes of status epilepticus in patients with tuberous sclerosis complex

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 36 Egyptian 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), 5 patients 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.

Characteristics and predictors of progression in an Egyptian multiple sclerosis cohort: a multicenter registry study

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.

Pediatric-onset multiple sclerosis in Egypt: a multi-center registry of 186 patients

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±2.49 years), 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.

Development and validation of an Arabic-language headache questionnaire for population-based surveys

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.

Ocular motor tests in relapsing remitting multiple sclerosis

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.

Role of magnetic resonance spectroscopy in differentiating parkinsonian syndromes of various etiologies

WCN 2013 No: 382 Topic: 2 — Movement Disorders Long-term complications of Parkinsons 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 Parkinsons 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 Parkinsons disease (IPD), druginduced parkinsonism (DIP) and Wilsons 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 Parkinsons 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 Parkinsons 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 Parkinsons 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