Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson's disease in an Egyptian cohort.

Introduction: Parkinson's disease (PD) is the most common motor neurodegenerative disease worldwide. Given the complexity of PD etiology and the different metabolic derangements correlated to the disease, metabolomics profiling of patients is a helpful tool to identify patho-mechanistic pathways for the disease development. Dopamine metabolism has been the target of several previous studies, of which some have reported lower phenylalanine and tyrosine levels in PD patients compared to controls. Methods: In this study, we have collected plasma from 27 PD patients, 18 reference controls, and 8 high-risk controls to perform a metabolomic study using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Results: Our findings revealed higher intensities of trans-cinnamate, a phenylalanine metabolite, in patients compared to reference controls. Thus, we hypothesize that phenylalanine metabolism has been shifted to produce trans-cinnamate via L-phenylalanine ammonia lyase (PAL), instead of producing tyrosine, a dopamine precursor, via phenylalanine hydroxylase (PAH). Discussion: Given that these metabolites are precursors to several other metabolic pathways, the intensities of many metabolites such as dopamine, norepinephrine, and 3-hydroxyanthranilic acid, which connects phenylalanine metabolism to that of tryptophan, have been altered. Consequently, and in respect to Metabolic Control Analysis (MCA) theory, the levels of tryptophan metabolites have also been altered. Some of these metabolites are tryptamine, melatonin, and nicotinamide. Thus, we assume that these alterations could contribute to the dopaminergic, adrenergic, and serotonergic neurodegeneration that happen in the disease.

Reliability and validity of the Arabic version of brief international cognitive assessment for multiple sclerosis in Egyptian pediatric multiple sclerosis patients.

BACKGROUND & OBJECTIVES: About one-third of pediatric-onset MS (POMS) patients report cognitive impairment. This case-control study aimed to assess the reliability and validity of the Arabic version of the Brief International Cognitive Assessment for MS (BICAMS) in Egyptian POMS patients. METHODS: A case-control study was conducted on 30 POMS patients aged 9 to 17 years old and 30 healthy controls. Both groups underwent the following tests: neuropsychological testing using the BICAMS-validated Arabic version battery involving 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 and controls 2 weeks following the primary evaluation. Mean variances between both groups were evaluated, controlling for age, gender, and educational level. RESULTS: MS patients scored significantly lower on the SDMT, CVLT-II, and BVMT-R tests than healthy controls (P-value <0.001). Test-retest reliability was satisfactory for SDMT, CVLT-II total, and BVRT-R in MS patients and controls with r values of 0.73, 0.83, and 0.80, respectively. CONCLUSION: BICAMS is a feasible approach to cognitive screening in POMS and adults. The Arabic version of BICAMS is a reliable and valid tool for the cognitive assessment of pediatric MS patients in different clinical and research settings.

Hope for brain health: impacting the life course and society.

Hope is a cognitive process by which an individual can identify their personal goals and develop actionable steps to achieve results. It has the potential to positively impact people's lives by building resilience, and can be meaningfully experienced at both the individual and group level. Despite this significance, there are sizable gaps in our understanding of the neurobiology of hope. In this perspective paper, the authors discuss why further research is needed on hope and its potency to be harnessed in society as a "tool" to promote brain health across healthy and patient populations. Avenues for future research in hope and the brain are proposed. The authors conclude by identifying strategies for the possible applications of hope in brain health promotion within the areas of technology, arts, media, and education.

Clinical and paraclinical predictors of early neurological deterioration and poor outcome in spontaneous intracerebral hemorrhage.

Background: Spontaneous intracerebral hemorrhage (sICH) is the second most common form of stroke. It is a major cause of morbidity and mortality. Several clinical and radiological parameters are related to its poor outcome. The aim of this study is to elucidate the clinical, laboratory, and radiological factors associated with early neurological deterioration and poor outcome in patients with ICH. Results: seventy patients diagnosed with sICH were evaluated within the first 72 h from the onset of symptoms by Clinical, radiological, and laboratory parameters. Patients were assessed for early neurological deterioration (END) during the hospital stay (up to 7 days from admission) using Glasgow coma scale (GSC), and the National Institutes of Health Stroke Scale (NIHSS), and within 3 months from stroke onset using modified Rankin scale (mRS). ICH score and Functional Outcome in Patients with Primary Intracerebral Hemorrhage (FUNC) Score were calculated for prognostication. 27.1% and 71.42% of patients had END and showed unfavorable outcome, respectively. Clinical indices, as NIHSS > 7 on admission and age > 51 years, radiological characteristics, as large hematoma size, leukoaraiosis, and mass effect detected on CT scan, as well as serum biomarkers; serum urea level > 50 mg/dL, high neutrophil:lymphocyte ratio on admission, high ALT and AST, as well as low total, LDL, and HDL cholesterol levels, all were significantly associated with poor outcome in the patients. Stepwise multivariate logistic regression analysis found the presence of aspiration to be an independent predictor of END, and the scores of NIHSS > 7 on admission, age > 51 years, and urea level > 50 mg/dL were independent predictors of poor outcome. Conclusions: There are several predictors for END as well as poor outcome in ICH. Some are clinical, others are radiological and laboratory. Aspiration was an independent predictor of END during hospital stay (3-7 days) in patients with ICH, while older age, high NIHSS and urea level on admission were independent predictors of poor outcome.

Management of rare movement diseases in different world regions.

To evaluate the management of rare movement disorders (RMD) at the international level and identify care needs to be addressed, the Rare Movement Disorders Study Group of the International Parkinson and Movement Disorders Society (MDS) has conducted an exploratory survey. We sent an online survey to experts in Africa, Asia, Oceania and American continents following the classification of the MDS Regional Sections: Africa, Asia and Oceania (A&O), and Pan-America. We did not include Europe as the European Reference Network for Rare Neurological Diseases recently performed a similar care needs survey across European countries. We obtained responses from experts from 20 African, 26 A&O and 19 Pan-American countries. According to the respondents, only 55% of African countries had movement disorders experts, while these were present in 96% of A&O and 91% of Pan-American. Access to care for patients with RMD was stated difficult in 70% of African, 54% of A&O, and 65% of Pan-American countries. Africa was the region with greatest difficulties in accessing diagnostic tests. However, in Pan-America and A&O, large inequalities were observed between countries with quite variable access to therapeutic options such as deep brain stimulation. The survey results reflect wide variability in the management of RMD and provide evidence that a worldwide care-focused network is highly warranted. Scientific and medical organisations should raise awareness of deficits in managing RMD and care disparities among regions. The goals should be to facilitate the training of professionals, establish improvement strategies, and increase support and budgeting for these diseases.

Validation of the Arabic Version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale.

BACKGROUND: The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has become the gold standard for evaluating different domains in Parkinson's disease (PD), and it is commonly used in clinical practice, research, and clinical trials. OBJECTIVES: The objectives are to validate the Arabic-translated version of the MDS-UPDRS and to assess its factor structure compared with the English version. METHODS: The study was carried out in three phases: first, the English version of the MDS-UPDRS was translated into Arabic and subsequently back-translated into English by independent translation team; second, cognitive pretesting of selected items was performed; third, the Arabic version was tested in over 400 native Arabic-speaking PD patients. The psychometric properties of the translated version were analyzed using confirmatory factor analysis (CFA) as well as exploratory factor analysis (EFA). RESULTS: The factor structure of the Arabic version was consistent with that of the English version based on the high CFIs for all four parts of the MDS-UPDRS in the CFA (CFI ≥0.90), confirming its suitability for use in Arabic. CONCLUSIONS: The Arabic version of the MDS-UPDRS has good construct validity in Arabic-speaking patients with PD and has been thereby designated as an official MDS-UPDRS version. The data collection methodology among Arabic-speaking countries across two continents of Asia and Africa provides a roadmap for validating additional MDS rating scale initiatives and is strong evidence that underserved regions can be energically mobilized to promote efforts that apply to better clinical care, education, and research for PD. © 2022 International Parkinson and Movement Disorder Society.

Parkinson's Disease in the Middle East, North Africa, and South Asia: Consensus from the International Parkinson and Movement Disorder Society Task Force for the Middle East.

BACKGROUND: Understanding the regional needs and available healthcare resources to treat Parkinson's disease (PD) is essential to plan appropriate future priorities. The International Parkinson and Movement Disorder Society (MDS) Task Force for the Middle East was established to raise awareness and promote education across the region on PD and other movement disorders. Broadly, the task force encompasses the countries of the Middle East but has included North Africa and South Asia as well (MENASA). OBJECTIVE: To create a list of needs and priorities in the advancement of PD in MENASA countries based on consensuses generated by the MDS task force for the Middle East. METHODS: A Strengths Weaknesses-Opportunities-Threats (SWOT) analysis was conducted by the task force members to generate consensus about PD care this region. RESULTS: Eight overarching principles emerged for the consensus statement on current needs: more movement disorders specialists, multidisciplinary care, accurate epidemiologic data, educational programs, availability of drugs, and availability of more advanced therapy, enhanced health care resources and infrastructure, and greater levels of awareness within the general population and among health care professionals. CONCLUSION: This pilot study sheds light on unmet needs for providing care to people with PD in the MENASA region. These data offer directions on priorities to increase awareness of PD, to develop better infrastructure for research and management of PD, to foster healthcare policy discussions for PD and to provide educational opportunities within these countries.

Trans-orbital sonography versus visual evoked potentials in acute demyelinating optic neuritis.

Optic neuritis (ON) is an inflammatory demyelinating condition that causes acute - usually monocular - visual loss. It is highly associated with multiple sclerosis (MS). In general, ON is a clinical diagnosis based upon the history and examination findings. OBJECTIVE: The aim was to assess the diagnostic accuracy of measuring optic nerve sheath diameter (ONSD) by ultrasound in acute optic neuritis. METHODS: This is a prospective observational study with matched controls carried out on 25 patients and 25 controls. All patients presented with first attack of an acute demyelinating ON. Both patients and controls were submitted to clinical assessment, pattern and flash visual evoked potential and trans-orbital sonography (TOS) to measure the optic nerve sheath diameter (ONSD). RESULTS: The ONSD was significantly thicker in patients with unilateral (0.6 ± 0.05 cm) and bilateral (0.6 ± 0.1 cm) optic neuritis compared to controls (0.52 ± 0.06 cm). P-value was < 0.001 and 0.04 respectively, with a cutoff value 0.57 cm. A significant negative correlation was found between the thickness of the ONSD and the visual acuity (r= -0.613, P-value <0.05). No correlation was found between the age of the patients and ONSD or between ONSD and latency of P-VEP. TOS showed 68% sensitivity and 88% specificity in diagnosing cases of ON. CONCLUSION: ONSD measured by TOS is a noninvasive, inexpensive bed-side test, which represent a supporting tool to confirm the clinical diagnosis of ON. Yet its sensitivity and specificity are lower than P-VEP.

Occupational metals exposure and cognitive performance among foundry workers using tau protein as a biomarker.

INTRODUCTION: Human exposure to heavy metals is a potential risk for developing cognitive impairment. Aluminum (Al) foundry is one of industries that involve occupational exposure to different metals. AIM OF THE WORK: to evaluate the cognitive performance of Aluminum foundry workers in relation to different metals exposure. MATERIALS AND METHODS: a cross sectional study conducted on 75 Al foundry workers and 75 non-occupationally exposed subjects as controls. Personal interview with specially designed questionnaire, Assessment of cognitive functions done using Montreal cognitive assessment (MocA), Stress, depression and sleep were also assessed. Serum levels of Aluminum (AL), Lead (Pb), manganese (Mn), Zinc (Zn) and tau protein were measured. RESULTS: Exposed group showed significant increase in serum levels of Aluminum, lead, Manganese and tau protein, p value < 0.005 (mean ±â€¯SD 0.56 ±â€¯0.18, 22.3 ±â€¯5.01, 42.04 ±â€¯7.4, 1.53 ±â€¯0.58 Vs 0.36 ±â€¯0.11, 13.4 ±â€¯1.29, 39.4 ±â€¯4.4, 1.03 ±â€¯0.44 respectively) with significant decrease of zinc level compared to control (mean ±â€¯SD 46.4 ±â€¯5.2 Vs 88.8 ±â€¯6.04, p value 0.005). There was a significant decrease MocA scores among exposed population, (mean ±â€¯SD 24.4 ±â€¯3.4 compared to 28.4 ±â€¯1.3 in non exposed, p value < 0.005). which was affected by serum levels of lead, aluminum, manganese and tau protein (ß -0.165, -8.958, -.286, -2.341 respectively and p < 0.005).Stress scores was higher in exposed workers than control but not affecting cognitive performance. CONCLUSION: occupational exposure to metals can cause cognitive dysfunction which may be subtle, so there is a need for formal cognitive testing at baseline, and on regular intervals during working period. Serum tau protein could be used as a prognostic biomarker for the hazardous effect of occupational exposure to these metals on the neuronal cells.

Validation of Montreal Cognitive Assessment-Basic in a sample of elderly Egyptians with neurocognitive disorders.

BACKGROUND AND OBJECTIVES: Montreal Cognitive Assessment-Basic (MoCA-B) is a modified version of the MoCA that is especially suitable for use in elderly subjects with low education. The Authors translated the tool into Arabic and they aimed at validation of this tool in a sample of elderly Egyptians. METHODS: The study included 93 patients, 60 years and older, fulfilling the DSM-5 criteria of Mild Neurocognitive Disorder (NCD) (39 patients) and Major Neurocognitive Disorder (54 patients) that were compared to 112 community dwelling elder subjects. All subjects were assessed using the MoCA-B, Mini-Mental State Examination (MMSE), and the Clinical Dementia Rating Scale (CDR) in addition to the required laboratory and radiological investigations. RESULTS: MoCA-B demonstrated good internal consistency (Cronbach's alpha = 0.915) and content validity in discrimination between normal and diseased subjects. It showed superior sensitivity and specificity when compared to MMSE in screening for Mild NCD (AUC MoCA-B = 0.988 versus MMSE = 0.939). The recommended cut-off was 21/22 with sensitivity of 92.5% and specificity of 98.2% for detecting Mild NCD and 16/17 with sensitivity of 90.7% and specificity of 97.4% for detecting Major NCD (dementia). CONCLUSION: The Arabic MoCA-B is a valid cognitive assessment tool in elderly Egyptian subjects.

Targeting Future Customers: An Introductory Biobanking Course for Undergraduate Students of Life Sciences.

INTRODUCTION: Biobanking is a relatively new concept in the Arab region. Targeting different stakeholders to introduce the concept of biobanking and develop an acceptance of it among them is important for the growth of biobanking in the region. Undergraduate students of life sciences represent an important segment of stakeholders, since they constitute potential future biobank customers. Limited funding, lack of awareness of the existence of the term "biobanking" itself among these students, and questions regarding best marketing strategies presented challenges to planning for the most effective message delivery to this target group. METHODS: A specific course was designed for undergraduate students of life sciences, which was conducted at the Faculty of Medicine, Cairo University, Egypt. The course was conducted twice in 2016 and included lectures covering biobanking, quality, ethics, information technology, and translational research. Facebook and word-of-mouth were used for marketing and advertising. RESULTS: A total number of 125 participants attended both courses cumulatively. Facebook appeared to have been an effective marketing outlet, especially when paid advertisements were used. Evaluation of knowledge, measured using a pretest and posttest, demonstrated some improvement in knowledge of participants. Evaluation forms filled after the course showed positive attitude toward content and message delivery by a majority of participants. Facebook was also used as an evaluation method through analysis of engagement with posts created after course completion. CONCLUSIONS: Biobanking education can be carried out effectively with limited resources. Understanding the needs of the target group and using appropriate methods of communication are essential prerequisites to a well-tailored curriculum and effective message delivery. Using Facebook appears to be an effective and affordable method of communication and advertising. Targeting undergraduate students of life sciences interested in research is a good investment and can be very effective in increasing awareness about biobanking inside the research community.

Enhancement of neural regeneration after spinal cord injury using muscle graft in experimental dogs.

AIMS: Spinal cord injuries (SCIs) can cause severe disability or death. The principal treatments for traumatic SCI include surgical stabilization and decompression. Using muscle as a scaffold is a new approach. The aim of this work is to evaluate the clinical efficacy of muscle graft as a scaffold for the growing axons organizing their growth, preventing gliosis in the damaged area and enhancing neural recovery in canine model of traumatic spinal cord injury. METHODS: 14 dogs were divided into group I (Control group) 4 control dogs subjected to Sham operation, group II (Trauma control group) 5 dogs subjected to dorsal laminectomy with excision of 1 cm segment of the spinal cord and group III (Muscle graft group) 5 dogs subjected to dorsal laminectomy then muscle graft was taken from the longissimus thoraces and inserted into the spinal cord gap. The animals of all groups were euthanatized after 8 weeks. Olby and modified Tarlov scores were used to clinically evaluate the therapeutic effects. Spinal cord specimens were subjected to histological, morphometric and statistical studies. RESULTS: Olby and modified Tarlov scores revealed significant clinical improvement in the muscle graft group. Histological sections showed overgrowth of axons on the muscle graft and the sections started to organize as central gray matter and peripheral white matter. CD44 & CD105 stains were positive for endogenous stem cells. CONCLUSIONS: This study proved the clinical efficacy of muscle grafting as a tool for induction of neuroregeneration after traumatic spinal cord injury.

Meta-Analysis of Creatine for Neuroprotection Against Parkinson's Disease.

BACKGROUND: Creatine is an antioxidant agent that showed neuroprotective effects in animal models of Parkinson's disease (PD). Creatine was selected by the National Institute of Neurological Disorders and Stroke as a possible disease modifying agent for Parkinson's disease. Therefore, many clinical trials evaluated the efficacy of creatine for patients with PD. The aim of this systematic review and meta-analysis is to synthesize evidence from published randomized controlled trials (RCTs) about the efficacy of Creatine for patients with PD. METHODS: We followed PRISMA statement guidelines during the preparation of this systematic review and meta-analysis. A computer literature search for PubMed, EBSCO, web of science and Ovid Midline was carried out. We included RCTs comparing creatine with placebo in terms of motor functions and quality of life. Outcomes of total Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS I, UPDRS II, and UPDRS III were pooled as mean difference (MD) between two groups from baseline to the endpoint. Statistical heterogeneity was assessed by visual inspection of the forest plot and measured by chi-square and I square tests. RESULTS: Three RCTs (n=1935) were included in this study. The overall effect did not favor either of the two groups in terms of: UPDRS total score (MD 1.07, 95% CI [3.38 to 1.25], UPDRS III (MD 0.62, 95% CI [2.27 to 1.02]), UPDRS II (MD 0.03, 95% CI [0.81 to 0.86], or UPDRS I (MD 0.03, 95% CI [0.33 to 0.28]). CONCLUSION: Current evidence does not support the use of creatine for neuroprotection against PD. Future well-designed, randomized controlled trials are needed.

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.

Epilepsy and antiepileptic drugs: risk factors for atherosclerosis.

INTRODUCTION: Epilepsy is a chronic disease that affects metabolism either alone or through the antiepileptic drug (AED) treatment. A risk of atherosclerosis has been found in epileptic patients. AIM: Prove the potential role of epilepsy and/or its treatment as atherosclerotic risk factors. SUBJECT AND METHODS: Forty Egyptian patients with primary idiopathic epilepsy were compared to 20 healthy controls. B-mode ultrasound examination of the common carotid artery intima-media thickness (CCA IMT), measurement of serum lipid profile, fibrinogen and high sensitive C-reactive protein were performed to both groups. RESULTS: Patients had significantly increased right and left CCA IMT (p < 0.05); elevated levels of HDL (p < 0.01) and hs-CRP (p = 0.009) in comparison to control subjects. Positive correlation was found between IMT and hs-CRP (p < 0.05) as well as fibrinogen level (p < 0.05). Carbamazepine level was positively correlated to triglycerides (r = 0.748, p = 0.013) and Valproate level was positively correlated to hs-CRP serum level (r = 0.556, p = 0.032). CONCLUSION: Epilepsy and AED's are potential risk factors for atherosclerosis. Weak relation between epilepsy and/or AED's and lipid profile was found. Hs-CRP may be implicated in atherosclerosis in epileptic patients.