Muhammad Saad Yousuf

Impact of Progression of Parkinson’s Disease on Drooling in Various Ethnic Groups

Background/Aims: Drooling or sialorrhea is a common non-motor symptom of Parkinson’s disease (PD), and is reported by 35–75% of patients. Drooling is primarily due to impaired swallowing rather than hypersecretion of saliva. In this study, we examined the prevalence of drooling in PD and its relation to various factors such as age, stage of disease, gender and ethnicity. Methods: A retrospective cohort chart analysis of 307 patients with idiopathic PD was conducted. These patients were seen in the Parkinson’s Disease and Movement Disorders Clinic between 2005 and 2010. Results: 123 (40%) patients exhibited drooling. No correlation between age and development of drooling was observed. However, gender was found to be a significant factor in developing sialorrhea. Males are twice as more likely to develop sialorrhea than females. In addition, drooling becomes more prevalent with disease progression; Hoehn and Yahr stage 4 patients being the most at risk. Ethnicity and immigration status have no relationship in developing drooling. Conclusions: Sialorrhea is seen in a significant number of PD patients. This study, to the best of our knowledge, is the most extensive clinical assessment of drooling in PD to date.

Prevalence and relation of dementia to various factors in Parkinson's disease

Aims:  Parkinsons disease is a chronic neurodegenerative disorder characterized by bradykinesia, rigidity, and resting tremor. Dementia, among its non‐motor symptoms, is a debilitating complication affecting intellectual functioning. The aim of the present study was to determine the prevalence of dementia in Parkinsons disease and its relation to age, gender and stage of the disease.

Prevalence of nocturia in Parkinson's disease patients from various ethnicities

Abstract Objectives: One of the most common non-motor symptoms in Parkinson’s disease (PD) is nocturia. This paper seeks to address the prevalence of nocturia in PD and correlate it to various factors such as gender, Hoehn and Yahr (H&Y) stage, age, and ethnicities. Methods: In particular, 332 PD patients were seen in a community movement disorders clinic and their charts were analyzed from 2005 to 2010. Within this population, more than one-third (34·9%) patients were diagnosed with nocturia. Results: Age, gender, and PD stage were significant predictors of nocturia in PD. With every one-year increase in age, the odds of developing nocturia in PD increases by 3·1% while an increase in H&Y stage increases the odds of nocturia in PD by 1·645 times. Also, males had greater odds of experiencing nocturia in PD. Ethnicities alone were of no significant importance. However, after performing interaction analyses, Asian and Indian males, especially, were at significantly greater risk than other ethnicities. Discussion: Future research is indeed required to understand why certain ethnicities are especially at risk. Clinicians must also be aware of the epidemiology of nocturia in PD to prevent and treat this debilitating symptom.

The Role of Regulatory Transporters in Neuropathic Pain.

Neuropathic pain arises from an injury or disease of the somatosensory nervous system rather than stimulation of pain receptors. As a result, the fine balance between excitation and inhibition is perturbed leading to hyperalgesia and allodynia. Various neuropathic pain models provide considerable evidence that changes in the glutamatergic, GABAergic, and monoaminergic systems. Neurotransmitter reuptake transporter proteins have the potential to change the temporal and spatial profile of various neurotransmitters throughout the nervous system. This, in turn, can affect the downstream effects of these neurotransmitters and hence modulate pain. This chapter explores various reuptake transporter systems and implicates their role in pain processing. Understanding the transporter systems will enhance drug discovery targeting different facets of neuropathic pain.

The chloride co-transporters, NKCC1 and KCC2, in experimental autoimmune encephalomyelitis (EAE).

Patients with multiple sclerosis (MS) often complain of neuropathic pain. According to the Gate Control Theory of Pain, spinal networks of GABAergic inhibitory interneurons are important in modulating nociceptive inputs from the periphery. Na+-K+-2Cl- co-transporter 1 (NKCC1) and K+-Cl- co-transporter 2 (KCC2) generally dictate the tone of GABA/glycine inhibition by regulating intracellular chloride concentrations. In this study, we investigated the role of NKCC1 and KCC2 in neuropathic pain observed in the animal model, experimental autoimmune encephalomyelitis (EAE), a commonly used model to study the pathophysiology of MS. Quantitative real-time polymerase chain reactions (qRT-PCR) analysis revealed no change in NKCC1 mRNA transcripts in dorsal root ganglia throughout EAE disease course. However, NKCC1 and KCC2 mRNA levels in the dorsal spinal cord were significantly reduced at disease onset and peak only to recover by the chronic time point. Similarly, Western blot data revealed a significant downregulation of NKCC1 and KCC2 in the dorsal spinal cord at disease onset but an upregulation of NKCC1 protein in the dorsal root ganglia at this time point. Treatment with bumetanide, an NKCC inhibitor, had no effect on mechanical hypersensitivity seen in mice with EAE even though it reversed the changes in the levels of NKCC1 and KCC2. We noted that bumetanide treatment, while effective at reversing the changes in monomeric KCC2 levels was ineffective at reversing the changes in oligomeric KCC2 which remained repressed. These results indicate that mechanical hypersensitivity in EAE is not mediated by altered levels of NKCC1.

A chronic case of adult-onset Sandifer syndrome.

Sandifer syndrome (SS), named after Dr. Paul Sandifer, is a rare disorder usually occurring in infants and young children. It is primarily characterised by dystonic movements of head and neck associated with gastroesophageal reflux disease (GERD) and it is considered as a neurological disorder [1]. Very rarely SS has been recognized in adults, and to the best of our knowledge, only two case reports have been published in this regard [2, 3]. Shahnawaz et al. [2] reported a 58-year-old African woman with SS which acutely manifested itself 3 months prior to diagnosis. Dystonic symptoms of the disorder began in close proximity to her facial palsy. Somjit et al. [3] presented a case of a 27-year-old male with intellectual disability who had episodes of acute pain, and head and eye deviation to one side which was incorrectly diagnosed to have refractory partial seizures. We present an atypical case of SS in an adult male with a longstanding history of dystonic symptoms associated with GERD. In this regard, he remained undiagnosed and untreated for 21 years. A 61-year-old right-handed male was referred for symptoms of cervical dystonia. The patient complained of paroxysmal tightness affecting the left side of his neck and left shoulder, since he was 40 years old. During these episodes, he had the feeling that his neck was pulled towards the left side. Symptoms usually lasted for 15 min to half an hour, with occasional short episodes lasting only 2–3 min. From the onset to the time of diagnosis, these episodes occurred on average of 2 times per week. Further, they were associated with the symptoms of GERD (e.g., epigastric pain, burning, nausea, regurgitation,). Eating would trigger his GERD symptoms which originated in the epigastrium and spread towards his neck behind the sternum inducing the spasms of the muscles and pulling of neck. In between the episodes, he was normal and there was no effect of sensory tricks. Upon examination (see video) during one of his typical episodes, his head was being pulled towards his left side. There was a tilt of his head as well as spasms of muscles of the left side of neck including sternocleidomastoid and platysma (Fig. 1). There were spasms of the muscles of the antero-lateral compartment of the neck in the left side along with contraction of the scalene muscles. In between the spasm, patient’s head was slightly deviated to the opposite side which was a result of the compensatory mechanism causing lateral deviation. Moreover, tonic contraction of the right sternocleidomastoid was visible which might also be compensatory to the spasms. Simultaneously, he experienced epigastric pain, discomfort and burning. In between his typical episodes, his neurological examination was completely unremarkable. A routine EEG with one typical episode of his symptoms and a 48-hour EEG with two episodes of pseudodystonic symptoms induced by GERD were normal. Brain and spine MRI revealed no abnormality. He was further assessed by the gastroenterology consultation service in our hospital. A gastroscopy was unremarkable but barium swallow study revealed significant early termination of primary peristaltic wave. For GERD, he was prescribed Electronic supplementary material The online version of this article (doi:10.1007/s10072-012-1005-1) contains supplementary material, which is available to authorized users.

Characterization of the Nile Grass Rat as a Unique Model for Type 2 Diabetic Polyneuropathy.

Type 2 diabetes (T2D) has reached pandemic proportions worldwide. Almost half of T2D patients suffer from polyneuropathy that can present as paresthesia, hyperalgesia, allodynia, or hypoesthesia. Therapeutic treatment options are largely incomplete, suggesting new avenues of research are needed. Herein, we introduce the African Nile Grass rat (NGR), which develops T2D solely by diet manipulation, as a novel T2D polyneuropathy model. The purpose of this study was to first characterize T2D-induced polyneuropathy in the NGRs before highlighting their strength as a potential prediabetic model of T2D. NGRs with long-term T2D exhibit hallmark features of polyneuropathy such as decreased motor nerve conduction velocity, intraepidermal denervation, and hyposensitivity to noxious mechanical and thermal stimulation. At the dorsal root ganglia, T2D neurons have altered sodium channel expression, specifically increased Nav1.7 and Nav1.9, and their surrounding satellite glial cells express glial fibrillary acidic protein. Now that these T2D NGRs have been characterized and shown to have a similar presentation to human and other animal models of T2D, the strength of this diet-induced model can be exploited. The prediabetic changes can be observed over their long progression to develop T2D which may allow for a therapeutic window to prevent T2D before permanent damage occurs.

DOPA-sparing strategy in the treatment of young onset Parkinson's disease

Context: Late onset Parkinsons disease (LOPD) is a neurodegenerative disorder afflicting individuals of ages 60 and older. However, 5–10% of cases can begin earlier between the ages 20 to 40, and are classified as young onset Parkinson disease (YOPD). Aim: In turn, this study aims to observe the trend in the choice of drug administered to patients with both YOPD and LOPD, with particular emphasis on this trend in its relation to the practice background of the neurologist. Settings and Design: A cross-sectional study was conducted in a community based Parkinsons disease and movement disorder clinic. Statistical Analysis Used: Using a retrospective chart review data was obtained and analysed. Results: The results showed that 83% of general neurologists prescribed levodopa to their patients with YOPD, whereas movement-disorder specialists took a different approach altogether. They opted not to use levodopa and, in its stead, prescribed a mixture of alternate drugs.