Ali S. Shalash

Effect of high‐frequency subthalamic neurostimulation on gait and freezing of gait in Parkinson's disease: a systematic review and meta‐analysis

The aim of this meta‐analysis was to summarize the short‐ and long‐term effects of bilateral deep brain stimulation of the subthalamic nucleus (STN‐DBS) on gait and freezing of gait (FOG) in Parkinsons disease and to detect predictors of post‐stimulation outcome. A comprehensive review of the literature was conducted up to October 2015 using Medline Ovid databases for studies analyzing the effect of bilateral STN‐DBS on FOG and/or gait. Sixteen studies with available data for the gait item (no. 29) of the Unified Parkinsons Disease Rating Scale (UPDRS) and six studies with the FOG item (no. 14) were included. Data were summarized for the following follow‐up periods: 6–15, 24–48 and >48 months. For the medication (Med)‐Off/stimulation(Stim)‐On condition compared with baseline Med‐Off, STN‐DBS significantly improved gait on average from 2.43 to 0.96, 2.53 to 1.31 and 2.56 to 1.40 points at 6–15, 24–48 and >48 months, respectively (P < 0.05). Pre‐operative levodopa responsiveness of UPDRS‐III and Med‐Off severity of gait were the predictors of this beneficial effect. STN‐DBS significantly improved FOG for the Med‐Off/Stim‐On condition compared with baseline on average from 2.26 to 0.82, 2.43 to 1.13 and 2.48 to 1.38 points at 6–15, 24–48 and >48 months, respectively (P < 0.05). There was no significant effect in the Med‐On/Stim‐On condition. This meta‐analysis showed a robust improvement of gait and FOG by STN‐DBS for more than 4 years in the Med‐Off/Stim‐On condition. No beneficial effect was found for the On state of medication. Pre‐operative levodopa responsiveness of global motor performance (UPDRS‐III) is the strongest predictor of the effect of deep brain stimulation on gait.

Effect of intranasal stem cell administration on the nigrostriatal system in a mouse model of Parkinson's disease

Parkinsons disease (PD) is the second most common neurodegenerative disease worldwide. It affects the locomotor system, leading to a final severe disability through degeneration of dopaminergic neurons. Despite several therapeutic approaches used, no treatment has been proven to be effective; however, cell therapy may be a promising therapeutic method. In addition, the use of the intranasal (IN) route has been advocated for delivering various therapies to the brain. In the present study, the IN route was used for administration of mesenchymal stem cells (MSCs) in a mouse model of PD, with the aim to evaluate IN delivery as an alternative route for cell based therapy administration in PD. The PD model was developed in C57BL/6 mice using intraperitoneal rotenone administration for 60 consecutive days. MSCs were isolated from the mononuclear cell fraction of pooled bone marrow from C57BL/6 mice and incubated with micrometer-sized iron oxide (MPIO) particles. For IN administration, we used a 20 µl of 5×105 cell suspension. Neurobehavioral assessment of the mice was performed, and after sacrifice, brain sections were stained with Prussian blue to detect the MPIO-labeled MSCs. In addition, immunohistochemical evaluation was conducted to detect tyrosine hydroxylase (TH) antibodies in the corpus striatum and dopaminergic neurons in the substantia nigra pars compacta (SNpc). The neurobehavioral assessment revealed progressive deterioration in the locomotor functions of the rotenone group, which was improved following MSC administration. Histopathological evaluation of brain sections in the rotenone+MSC group revealed successful delivery of MSCs, evidenced by positive Prussian blue staining. Furthermore, rotenone treatment led to significant decrease in dopaminergic neuron number in SNpc, as well as similar decrease in the corpus striatum fiber density. By contrast, in animals receiving IN administration of MSCs, the degeneration caused by rotenone treatment was significantly counteracted. In conclusion, the present study validated that IN delivery of MSCs may be a potential safe, easy and cheap alternative route for stem cell treatment in neurodegenerative disorders.

Intracranial Steno-Occlusive Arterial Disease and its Associations in Egyptian Ischemic Stroke Patients

Background and Purpose— Intracranial arterial steno-occlusive disease is prevalent among non-white populations. We explored whether a similar pattern exists in Egyptians and assessed its clinical-radiological associations. Methods— Consecutive acute ischemic stroke patients were recruited for 6 months and had magnetic resonance imaging/magnetic resonance angiography of brain within 2 days of the event. Magnetic resonance angiography was analyzed for significant stenosis (>50%), flow gaps, and complete occlusions in the major intracranial arteries. Results— A total of 143 patients completed the study (62.4±12.6 years, 58.7% males). Magnetic resonance angiography showed symptomatic arterial stenosis in 27.3%, asymptomatic stenosis in 16.1%, and occlusions in 23.7% patients. Carotid duplex showed stenosis >70% in only 7.7% patients. Patients with intracranial arterial steno-occlusive disease had higher National Institutes of Health Stroke Score at admission (10.9±7 versus 8±5.6; P=0.01). Conclusion— Symptomatic and asymptomatic intracranial arterial steno-occlusive disease was prevalent in this Egyptian acute stroke sample. This might have important implications on stroke management in this population.

Retinal changes in children and adolescents with sickle cell disease attending a paediatric hospital in Cairo, Egypt: risk factors and relation to ophthalmic and cerebral blood flow

BACKGROUND Sickle cell disease (SCD) is characterised by occlusion of small blood vessels. This study aimed to assess retinal changes in patients with SCD and its correlation with time-averaged mean flow velocity (TAMV) in middle cerebral arteries (MCA) and ophthalmic arteries (OA). METHODS Sixty SCD patients (aged 3-18 years) attending a paediatric hospital in Cairo, Egypt, during March 2010 to November 2011, were compared with 30 healthy controls. All underwent clinical and fundus examination by indirect ophthalmoscopy, and assessment of TAMV in MCAs and OAs by transcranial Doppler, repeated 1 year later for those with conditional velocities. RESULTS HbS/β was diagnosed in 32 patients and HbSS in 28; 50 patients had normal fundus and 10 had bilateral non-proliferative retinopathy. Risk factors for retinopathy included HbSS, age, previous stroke, non-compliant hydroxyurea (HU) therapy, frequency of sickling crises and HbS level. TAMVs were increased in MCAs, but not in OAs, in sicklers. TAMVs in MCAs and OAs increased with non-compliant HU therapy, previous stroke, age, frequency of sickling crises and level of HbS. No significant interhemispheric difference was found. CONCLUSION Sickle retinopathy was correlated with TAMV in MCAs but not in OAs. A significant difference was found between initial and follow-up TAMVs in the MCAs, after 1 year of regular HU and transfusion therapy, in those with conditional velocities.

Auditory- and Vestibular-Evoked Potentials Correlate with Motor and Non-Motor Features of Parkinson’s Disease

Degeneration of several brainstem nuclei has been long related to motor and non-motor symptoms (NMSs) of Parkinson’s disease (PD). Nevertheless, due to technical issues, there are only a few studies that correlate that association. Brainstem auditory-evoked potential (BAEP) and vestibular-evoked myogenic potential (VEMP) responses represent a valuable tool for brainstem assessment. Here, we investigated the abnormalities of BAEPs, ocular VEMPs (oVEMPs), and cervical VEMPs (cVEMPs) in patients with PD and its correlation to the motor and NMSs. Fifteen patients diagnosed as idiopathic PD were evaluated by Unified Parkinson’s Disease Rating Scale and its subscores, Hoehn and Yahr scale, Schwab and England scale, and Non-Motor Symptoms Scale. PD patients underwent pure-tone, speech audiometry, tympanometry, BAEP, oVEMPs, and cVEMPs, and compared to 15 age-matched control subjects. PD subjects showed abnormal BAEP wave morphology, prolonged absolute latencies of wave V and I–V interpeak latencies. Absent responses were the marked abnormality seen in oVEMP. Prolonged latencies with reduced amplitudes were seen in cVEMP responses. Rigidity and bradykinesia were correlated to the BAEP and cVEMP responses contralateral to the clinically more affected side. Contralateral and ipsilateral cVEMPs were significantly correlated to sleep (p = 0.03 and 0.001), perception (p = 0.03), memory/cognition (p = 0.025), and urinary scores (p = 0.03). The oVEMP responses showed significant correlations to cardiovascular (p = 0.01) and sexual dysfunctions (p = 0.013). PD is associated with BAEP and VEMP abnormalities that are correlated to the motor and some non-motor clinical characteristics. These abnormalities could be considered as potential electrophysiological biomarkers for brainstem dysfunction and its associated motor and non-motor features.

Bee venom for the treatment of Parkinson’s disease: How far is it possible?

Parkinsons disease (PD) is the second most common neurodegenerative disease, characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta leading to depletion of striatal dopamine and motor symptoms as bradykinesia, resting tremors, rigidity, and postural instability. Current therapeutic strategies for PD are mainly symptomatic and may cause motor complications, such as motor fluctuations and dyskinesia. Therefore, alternative medicine may offer an effective adjuvant treatment for PD. Bee venom therapy (BVT) has long been used as a traditional therapy for several conditions, such as rheumatoid arthritis, asthma, and skin diseases. Experimental and clinical studies showed that BVT could be an effective adjuvant treatment for PD. Several mechanisms were suggested for these findings including the ability of BVT to attenuate neuroinflammation, inhibit apoptosis of dopaminergic neurons, protect against glutamate-induced neurotoxicity, and restore normal dopamine levels in the nigrostriatal pathway. In this article, we reviewed and summarized the literature regarding the potential of BVT for the treatment of PD.

Elevated Serum α-Synuclein Autoantibodies in Patients with Parkinson’s Disease Relative to Alzheimer’s Disease and Controls

Early diagnosis of neurodegenerative diseases is of paramount importance for successful treatment. Lack of sensitive and early biomarkers for diagnosis of diseases like Parkinson’s disease (PD) is a handicapping problem for all movement disorders specialists. Using serum autoimmune antibodies (AIAs) against neural proteins is a new promising strategy to diagnose brain disorders through non-invasive and cost-effective method. In the present study, we measured the level of AIAs against α-synuclein (α-syn), which is an important protein involved in the pathogenesis of PD. In our study patients with PD (46 patients), Alzheimer’s disease (AD) (27 patients) and healthy controls (20 patients) were evaluated according to their sera α-syn AIAs levels. Interestingly, α-syn AIAs were significantly elevated in PD group compared to AD and healthy controls, which advocates their use for diagnosis of PD.

Arabic cross cultural adaptation and validation of the National Institutes of Health Stroke Scale

INTRODUCTION The National Institutes of Health Stroke Scale (NIHSS), the most commonly used tool to quantify neurological deficit in acute stroke, was initially developed in English. We present our experience in developing and validating an Arabic version of the NIHSS (arNIHSS). METHODS RESULTS In 6months, 137 patients were recruited (mean age±standard deviation 62±12years; 48 women). For interrater agreement, weighted kappa value ranged from 0.36 to 0.66 and intraclass correlation coefficient (ICC) for the whole scale was excellent at 0.95 (95% confidence interval [CI] 0.94-0.97). For intrarater agreement, weighted kappa ranged from 0.52 to 1.0 and the ICC was 0.94 (95% CI 0.87-0.98). The construct validity of the arNIHSS is demonstrated by its correlation with the DWI-ASPECT and the 3months mRS score (Spearman correlation -0.46 and 0.58 respectively; P<0.001 for both). CONCLUSION We developed and validated a culturally adapted Arabic version of the NIHSS. Further validation in other Arab countries is recommended.

Tubulin and Tau: Possible targets for diagnosis of Parkinson’s and Alzheimer’s diseases

Neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by progressive neuronal loss and pathological accumulation of some proteins. Developing new biomarkers for both diseases is highly important for the early diagnosis and possible development of neuro-protective strategies. Serum antibodies (AIAs) against neuronal proteins are potential biomarkers for AD and PD that may be formed in response to their release into systemic circulation after brain damage. In the present study, two AIAs (tubulin and tau) were measured in sera of patients of PD and AD, compared to healthy controls. Results showed that both antibodies were elevated in patients with PD and AD compared to match controls. Curiously, the profile of elevation of antibodies was different in both diseases. In PD cases, tubulin and tau AIAs levels were similar. On the other hand, AD patients showed more elevation of tau AIAs compared to tubulin. Our current results suggested that AIAs panel could be able to identify cases with neuro-degeneration when compared with healthy subjects. More interestingly, it is possible to differentiate between PD and AD cases through identifying specific AIAs profile for each neurodegenerative states.

Self-reported quality of life of patients with multiple sclerosis with mild disability

Background The quality of life (QoL) of the patient is a reflection of the severity of multiple sclerosis (MS) and predicts its prognosis; it is related to various factors that vary across cultures. Objective The aim of the current study was to evaluate the QoL of ambulatory and mildly disabled patients with relapsing remitting multiple sclerosis (RRMS), and explore the related factors and cultural characteristics. Patients and methods Sixty Egyptian patients with a definitive diagnosis of RRMS were recruited and assessed for disability using Expanded Disability Status Scale, their QoL using Multiple Sclerosis Quality of Life Inventory (MSQLI), and depression using the Beck Depression Inventory scale. Patients’ QoL was compared with that of 30 matched controls. Results The QoL of MS patients was significantly impaired in all domains compared with that of controls (P<0.001), except for Social Functioning. Most of the physical components of the QoL were strongly correlated with Expanded Disability Status Scale, fatigue, and perceived cognitive impairment, and mental components were correlated with depression (P<0.001), fatigue, and perceived cognitive impairment. An overall 81% of MS patients had depression that correlated with disability (P=0.012) and fatigue (P=0.001), and correlated moderately with perceived cognitive impairment. Women reported more anxiety (P=0.038) and less perceived social support (P=0.012), whereas men stated more sexual dissatisfaction (P=0.001). Conclusion Mildly disabled Egyptian patients with RRMS have a high prevalence of depression and considerable impairment of mental and physical components of the QoL, such as disease disability, depression, fatigue, and perceived cognitive impairment.