Spinocerebellar ataxia type 12 (SCA12) is a progressive neurological disorder with a unique prevalence in North Indian population. Trinucleotide CAG repeat expansion beyond certain threshold (>43 repeats) in the upstream region of PPP2R2B gene is associated with cerebello-cortical atrophy in disease affected individuals. Patients with SCA12 predominantly manifest unique distinguishable feature of early slow and progressive action tremor in upper extremities followed by other variable symptoms such as mild to moderate gait ataxia, speech disturbances with tremulous voice, head tremor, and autonomic abnormalities. At present, there is no definite treatment available to cure this disease and the underlying disease mechanism at molecular level largely remains undetermined. This review focuses on epidemiology, clinico-genetic advancements, and therapeutics interventions emerged over the time in this field.

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Bupropion (BPP) was originally an antidepressant, but now it is also used for seasonal affective disorder and smoking cessation. The aim of this systematic review was to evaluate the clinical epidemiological profile, pathological mechanisms, and management of BPP-associated movement disorders. Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 63 reports of 710 cases from 16 countries were assessed. The movement disorders associated with BPP found clearly defined were: dyskinesia (8), dystonia (7), parkinsonism (7), myoclonus (6), tic (6), stuttering (3), rapid eye movement sleep disorders (2), and ballism (1); the not clearly defined cases included 488 tremors, 80 slurred speech, 48 ataxia, 20 abnormal movements, 19 falls, 4 akathisia, 3 dyskinesia, 2 hyperkinesia, 2 poor coordination, and the rest was only reported once (dystonia, myoclonus, motor tic, and rigidity). The mean age was 46 years (7–85 years). The male was predominant sex (52.77%). The mean BPP dose was 248.38 mg, and the most common indication was a major depressive disorder (73.68%). The average time of onset was 3.47 weeks and of recovery was 2.71 weeks. The most common management was BPP withdrawal. In the literature, the majority of the cases did not clearly report the clinical neurological examination and lacked electrodiagnostic studies. Future studies about adverse effects with BPP should describe at least the clinical characteristics and the physical exam of the individuals, especially when fall and slurred speech are observed.

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Gene therapy has proven its potential in treatment of several human diseases. Most recent method in a long line of genome-editing techniques is Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system. This CRISPR–Cas9 technology uses a ribonucleic acid (RNA)-guided deoxyribonucleic acid (DNA) endonuclease, Cas9, which induces double-strand breaks (DSBs) in target site. These DSBs are repaired by various cellular DNA repair mechanisms leading to changes in target sites. This revolutionary technique has unraveled several mysteries not only in pathogenesis of several human diseases but also proved its high potential in developing disease models ranging from cell lines to large animals. The number of neurodegenerative disorders linked with mutations has been increasing every day. Several such monogenic disorders provide opportunities for gene therapy using CRISPR–Cas9 method. Translational gap toward developing highly precise and personalized medicine for several neurodegenerative disorders has been reduced by CRISPR–Cas9 technology. Recent advancements in this technique have reduced the adverse effects on targets also. In this review, we have summarized recent achievements of CRISPR–Cas9 technology in common neurological disorders aiming clinicians to understand the technology.

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A scale is critical for an objective and standardized process in which the purpose involves measuring differences between various individuals and determining priorities such as primary treatment goals. The aim of this study was to describe and analyze the most common Parkinson’s disease (PD) scales already used for research and clinical practice. We searched three databases in an attempt to locate existing scales about PD published until 2017 in electronic form, only the articles in English, Spanish, and Portuguese were reviewed. In sum, 114 scales were evaluated and divided into 6 types representing a general evaluation, such as staging, health-related quality of life, evaluation of the impact on activities of daily living, loss of functionality aimed at evaluation of the signs and symptoms of the disease, evaluation of functioning and disability loss, and other specific evaluations. Other specific evaluations include the following: fear of falling, depression, psychosis, sleep, apathy and anhedonia, anxiety, dysautonomia, dyskinesia, fatigue, motor fluctuations, psychosocial problems, secondary levodopa effects, Scales for Outcomes in Parkinson’s disease (SCOPA) studies, and cognitive impairment screening. When required, more specific characteristics of each scale were included: time to apply, the number of items, advantage, and disadvantage. In the literature, there are a large number of scales, but the majority of them were created for other diseases and only later studied for PD. Also, more than half have only a small number of studies with psychometric evaluation and others can be used for only a specific portion of the general population due to their specific feature assessment or language availability.

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Thermoregulatory abnormalities, especially sweating disorders, are very common in Parkinson’s disease (PD). The estimated prevalence of sweating abnormalities ranges from 5.5% to 12.9% in de novo, newly diagnosed patients with PD and up to 64% during later stages of the disease. The range of thermoregulatory abnormalities in PD is broad, and includes hyperhidrosis, hypohidrosis, and hypothermia. In addition, the way in which these symptoms present themselves varies between patients and they can be chronic or fluctuating, local or generalized affecting the whole body, and related to motor complications or medication. Often there is a strong link to other autonomic symptoms, yet the exact pathogenesis behind these overlapping symptoms remains largely elusive, although current evidence points toward both central and peripheral involvement. Treatment remains difficult because of the lack of understanding of pathophysiology as well as specific clinical trials needed for evidence base. In this review, we have identified 43 studies in English language assessing sweating disorders in idiopathic PD. Here, we summarize knowledge gleaned from these reports and discuss current understanding of thermoregulatory dysfunction in PD, its phenomenology, pathophysiology, and management options.

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Parkinson’s disease is a common progressive neurodegenerative disease. Apart from pharmacological treatment, nonpharmacological management in the form of rehabilitation, counselling, and supportive care is an equally important therapeutic pillar. A MEDLINE search strategy using the following terms (1998–2019) was adopted for this review. Limits of “Human” and “English” were applied. Search terms included “Parkinson’s Disease” AND “rehabilitation,” “physical therapy,” “exercise therapy,” “physiotherapy,” and “dance.” Review articles, practice parameters, guidelines, systematic reviews, meta-analyses, randomized controlled trials, and cohort studies were included. Rehabilitation strategies in the management of Parkinson’s disease form a vital component of therapy. There is mounting evidence to support physical therapy in these patients. Rehabilitation should be offered to these patients right from the start to encourage an active lifestyle and to improve quality of life.

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OBJECTIVE: To elucidate the effect of step-synchronized vibration training using PDShoe on balance, gait, and quality of life in patients of Parkinson’s disease (PD) with freezing of gait (FOG).MATERIALS AND METHODS: In a pilot study, 17 patients of PD with FOG were recruited for step-synchronized vibration training. The training involved 10 sessions of gait training over 2 weeks. Each session included three 6-min bouts of walking with step-synchronized vibration applied to the second metatarsal head and medial surface of calcaneus. Participants were assessed with the Unified Parkinson’s Disease Rating Scale-III (UPDRS III), Timed Up and Go (TUG) test, Berg Balance Scale (BBS), Timed 10-Meter Walk Test, Freezing of Gait Questionnaire (FOG-Q), Falls Efficacy Scale-International (FES-I), and Parkinson’s Disease Questionnaire-39 (PDQ-39). Measurements were collected pre-intervention, post-intervention, and at a 2-week follow-up. Friedman test followed by Wilcoxon signed-rank test were used for statistical analysis.RESULTS: All participants completed the intervention without any adverse effects. Fifteen participants reported for a follow-up evaluation 2 weeks after intervention. There was statistically significant improvement in UPDRS III (P = 0.044) and significant improvement in TUG test (P = 0.005), BBS (P = 0.026), FES-I (P = 0.041), and PDQ-39 (P = 0.021) scores between pre and follow-up evaluations. No significant changes were seen in FOG-Q and Timed 10-Meter Walk Test.CONCLUSION: Step-synchronized vibration is a novel intervention to improve balance, gait, motor features, and quality of life in patients of PD with FOG. Further research is warranted to confirm the results found in this pilot study.

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Psychosis is a common and often debilitating non-motor symptom of Parkinson’s disease (PD). It typically manifests in the form of well-formed visual hallucinations and minor hallucinations, and, at times, can present with delusions and nonvisual hallucinations. Psychosis is associated with many adverse outcomes in PD, and for that reason, it is essential to recognize and treat the symptoms early. The objective of this review article is to highlight the phenomenology, diagnosis, and pathophysiology of PD-associated psychosis (PD-P) and discuss a step-by-step approach to its management. One of the critical steps in managing PD-P is the identification of potential non-PD causes of psychosis, which often require conservative measures. If no secondary causes are identified, pharmacotherapy should be considered. Role of several drugs including pimavanserin (the only FDA-approved agent for the treatment of PD-P), atypical antipsychotics such as quetiapine and clozapine, and cholinesterase inhibitors such as rivastigmine and donepezil are discussed in this review. In addition, we also highlight the potential role of noninvasive brain stimulation (electroconvulsive therapy and transcranial magnetic stimulation) for the treatment of medication-refractory psychosis.

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Tremor is now considered an important phenotypic feature of dystonia. Tremor in dystonia is of two types: dystonic tremor, where tremor occurs at the same site that involves dystonia, and tremor associated with dystonia, where tremor occurs at a site other than that involving the dystonic region. A patient may be found to have both the conditions together, and different syndromes are separated on clinical grounds. The aim of this review was to discuss the definition, clinical spectrum, pathophysiology, and treatment of dystonic tremor.

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Understanding of Huntington’s disease (HD) has been evolving since its early descriptions from nineteenth century. Significant breakthroughs into HD pathophysiology and therapeutic targets have been seen in last 50 years. Most of the publications in relation to HD are from European and American continents, indicating geographical higher prevalence. HD in India has been reported since early 1950s in the form of case reports and series, with exception of varying references in ancient Indian literature as “Tandavaroga.” In this review, we have amalgamated the various Indian publications on HD till date.

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INTRODUCTION: Ataxia telangiectasia (AT) is an autosomal-recessive disease, characterized by progressive cerebellar degeneration, mucocutaneous telangiectasia, immunodeficiency, recurrent sinopulmonary infections, sensitivity to radiation, and increased risk of malignancy. The objective of this study was to report the clinical profile of a large cohort of patients with AT seen in a tertiary care referral center. METHODS: This study was a chart review of 100 patients with AT seen by the department of neurology at the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India, which is a tertiary care referral center. Detailed demographic, clinical, laboratory, and electrophysiological data were collected from the case records. RESULTS: The mean age of presentation was 9.04 ± 3.52 years. Females (n = 40) had earlier age of presentation (8.87 ± 3.09 years) when compared to males (9.15 ± 3.80 years). The mean age for onset of illness was 3.9 ± 2.84 years, and the mean duration of illness was 4.81 ± 3.30 years. A positive family history was obtained in 20% and consanguinity in 60%. Oculomotor abnormalities included impaired pursuit and slow saccades in 60%, oculomotor apraxia in 84%, and nystagmus in 23%. All the patients had cerebellar ataxia. Extrapyramidal features such as dystonia, choreoathetosis, tremors, and myoclonus were observed in 31% of patients. CONCLUSION: Progressive cerebellar ataxia and telangiectasias were the consistent findings observed in all our patients. Dystonia and chorea were the other extrapyramidal features observed. Owing to increased risk of malignancies, screening should be an integral part of management.

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Syphilis is a well-known “great simulator/mimicker” of other diseases. Over the last decades, the clinical features of neurosyphilis have changed with an increasing percentage of atypical manifestations. In this context, movement disorders caused by neurosyphilis are rare and challenging to diagnose. This literature review aimed to evaluate the clinical epidemiological profile, pathological mechanisms, and historical features of neurosyphilis-associated movement disorders. Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 84 reports containing 168 cases who developed a movement disorder related to neurosyphilis were reported. The mean and the median reported ages were 40.50 (standard deviation [SD], 20.30) and 43 years (2.5–72.5 years). The predominant sex was male (79.16%). Argyll Robertson pupils were found in 54.90% of the individuals. The movement disorders reported were tremor, chorea, parkinsonism, ataxia, myoclonus, dystonia, athetosis, and ballism. In the literature, we have a large number of reports about movement disorder associated with neurosyphilis. But, in the majority of them, the individuals had the syphilitic diagnosis based on unspecific methods, electrodiagnostic studies were not performed, or penicillin therapy was unavailable. Also, we believe that any patient presenting with a movement disorder should have a thorough neurological examination of pupillary reflex, and if any abnormality is present, syphilitic laboratorial tests should be done.

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Although subcutaneously administered apomorphine is widely used as an effective adjunct therapy for Parkinson’s disease (PD), it was approved for use in India only in 2019. This review summarizes the history, pharmacology, clinical spectrum, indications, efficacy, and side effects of subcutaneous apomorphine use in patients with PD along with clinical recommendations for its use in Indian context. Intermittent subcutaneous apomorphine injection or continuous subcutaneous apomorphine infusion is effective adjunctive treatments for patients with advanced PD with levodopa-related refractory motor complications and some specific nonmotor symptoms (NMS) as growing evidence shows apomorphine also improves aspects of NMS of PD. Common side effects of subcutaneous apomorphine are skin nodules, nausea, and somnolence with incidence being higher with infusion than that with injection. Impulse control disorders and neuropsychiatric complications common to most dopamine agonists can also occur. As per National Institute for Health and Care Excellence (NICE), United Kingdom, apomorphine, as intermittent injection or continuous subcutaneous infusion, is one of the best medical therapies and may be considered before using deep brain stimulation (DBS) or levodopa/carbidopa intestinal gel (LCIG). Head-to-head open-label comparative multicenter data suggest that apomorphine is at least as effective as DBS or LCIG in relation to nonmotor and motor benefit. More studies are needed to reduce the paucity of apomorphine data in Indian population. We also discuss criteria to select one device therapy over another and newer apomorphine delivery strategies in the pipeline.

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Neurogenic orthostatic hypotension is a common disorder often seen in elderly patients affected with neurodegenerative disorders and peripheral neuropathies. Defective baroreflex-mediated sympathetic activation in response to standing results in neurogenic orthostatic hypotension. Lightheadedness, dizziness, blurring of vision, palpitations, and/or recurrent syncope in response to sudden postural change or prolonged standing are the characteristic symptoms presented by patients with orthostatic hypotension. Orthostatic symptoms may be further aggravated by certain medications, fluid depletion, food intake, increased temperature, or physical deconditioning. Bedside orthostatic test, head-up tilt table test, and 24-h ambulatory blood pressure monitoring are the important tests to diagnose orthostatic hypotension. Discontinuation of medications that cause or exacerbate orthostatic hypotension and non-pharmacological approaches should be initially tried to treat neurogenic orthostatic hypotension. If the patient does not have significant improvement, add-on pharmacotherapy should be administered. Midodrine, droxidopa, and fludrocortisone are the commonly administered medications for treating neurogenic orthostatic hypotension. Systematic reviews have shown that there is moderate level of evidence that droxidopa and midodrine improve orthostatic hypotension in the short term. Fludrocortisone is included in the treatment guidelines based on expert opinion, despite having low level of evidence. However, there is no much evidence for the long-term efficacy of any pharmacological agent used to treat orthostatic hypotension. Treatment of neurogenic orthostatic hypotension should be periodically assessed. Predominantly, it involves measuring symptomatic benefit including impact on activities of daily living as well as blood pressure monitoring.

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OBJECTIVES: To compare the sleep profiles of genetically proven cases of Huntington’s disease (HD) with healthy controls and to correlate the results of various sleep-related parameters with disease severity, duration, and length of cytosine–adenine–guanosine repeats.METHODS: This prospective study was conducted at the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India, which included 31 genetically confirmed patients with HD and 50 controls. All the subjects were evaluated for sleep disturbances using standardized sleep questionnaires (Pittsburgh Sleep Quality Index [PSQI] and Epworth Sleepiness Scale [ESS]).RESULTS: The mean age of the patients during the first consultation was 46.0±12.7 years (range: 28–80). The mean age at onset of symptoms was 40.5±13.8 years. Nineteen patients (61.2%) gave history of sleep disturbances. Symptom suggestive of rapid eye movement sleep behavior disorder was present in 8 patients (25.8%). Difficulty in falling asleep was the most common sleep-related disturbance reported by 16 patients (51.6%). The mean ESS score of the patients was 6.22±2.89 and that of the control population was 3.00±2.8 (P value < 0.001). The mean PSQI score of the patients was 8.90±3.50 and that of the control population was 3.3±2.9 (P value < 0.001).CONCLUSIONS: This study demonstrates sleep disturbances in patients with HD compared to healthy controls and the sleep disturbances correlated significantly with the disease duration, severity, and coexistent anxiety and depression.

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Movement Disorders are currently growing to be one of the major subspecialties of neurology worldwide, primarily by developments of research and therapeutics in this field. As any specialty grows, it leads to the formation of its society and the publication of journal to disseminate the knowledge. The International Parkinson’s Disease and Movement Disorders Society (IPMDS, formerly known as Movement Disorders Society) played its role with inception since 1980s. Further development of Movement Disorders subspecialty leads each region and country to have their own national societies and publications. Similarly, the seeds of Movement Disorders were sown in India in mid-1980s but it took a major stride in last few years with the formation of Movement Disorders Society of India (MDSI) in 2014 and following this, it is now at the crux of starting its journal—Annals of Movement Disorders (AOMD). This would be a right time to look back into the history of Indian Neurology with specific reference to the Movement Disorders and pen down these chronicles since the inception of modern neurology in India. The current chronicles of Indian Movement Disorders is penned based on personal interviews with various senior Movement Disorder specialists of India. However, it should also be remembered that many of the chronicles are limited by the memories of people and their biases with whom the interviews are conducted.

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Patients with Parkinson’s disease (PD) develop a range of non-motor symptoms (NMS). Sleep disturbance is one of the common NMS of PD and the onset of sleep disorders often precede the onset of motor symptoms of PD. Motor symptoms of PD often receive the main clinical focus and the sleep disturbances often go unnoticed in clinical practice. Given that the prevalence of PD is higher in the elderly population, primary care physicians, geriatricians, and gerontologists are usually the first point of contact for a majority of patients with PD. Because of this, it is important that they have a clear understanding about the diagnosis and management of the sleep disturbances in PD. This review provides an overview of the full spectrum of sleep disturbances in PD that includes insomnia, excessive daytime sleepiness, rapid eye movement sleep behavior disorder, restless leg syndrome, periodic limb movements, and obstructive sleep apnea. Although these sleep disorders may be primarily associated with PD, it is crucial to delineate the other treatable causes of sleep disturbances such as side effects of medications and physical symptoms not related to PD. This review highlights the major sleep disorders observed in patients with PD and succinctly discusses their management aspects. In addition, we have briefly described the effect of deep brain stimulation on the natural course of several sleep disorders in PD in this article.

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Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting 1%–2% people over the age of 65 years and up to 4% population over 85 years of age. Herein, we present four separate case-based scenarios commonly encountered in the neurology practice and provide the current evidence-based answers to commonly asked questions by patients, caregivers, and primary care physicians regarding the diagnosis and management of patients with PD, separating issues pertaining to early- versus late-onset PD, and management throughout various stages of disease. The discussion points within each case may apply across all cases.

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BACKGROUND: Non-motor symptoms (NMSs) were a real burden in Parkinson’s disease (PD) and contributed to severe disability, impaired quality of life (QoL), and shortened life expectancy. AIM: The aim of this study was to investigate the prevalence of NMSs in PD and their correlation of NMS with disease duration, severity, and Unified Parkinson's Disease Rating Scale (UPDRS) motor score and their impact on patient’s QoL. MATERIALS AND METHODS: This was a prospective cross-sectional study. Sixty-four patients who were diagnosed by United Kingdom Parkinson's Disease Brain Bank criteria were studied. Non-motor symptom scale (NMSS) analyzed NMS, and motor dysfunction was assessed by the UPDRS II and III during OFF condition and QoL by Parkinson’s Disease Questionnaire-39 (PDQ-39) questionnaire. RESULTS: The prevalence of NMS was 93.75% (n = 60). Most frequent NMS was difficulty in falling asleep (54.7%), urinary urgency (39%), and memory impairment (37.5%). Most disabling symptoms are difficulty in falling asleep (3.34 ± 4.1) and fatigue (2.48 ± 4.2). The total NMSS scores were correlated with Hoehn and Yahr stage, and Movement Disorder Society UPDRS and PDQ-39 scores, but not with duration of disease. Correlation between NMSS and PDQ-39 scores was stronger as compared to the relationship between UPDRS and PDQ-39 scores (r = 0.71 and 0.58, respectively, P = 0.00). CONCLUSION: This study showed the high prevalence of NMSs and value of NMS as predictors of QoL in patients with PD. Therefore, understanding the pathophysiology of these NMSs should be placed at the forefront to develop new therapeutic approaches by improving the QoL of patients with PD.

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Insidious-onset progressive dystonias are rarely described as a sequelae of stroke. Their pathological basis consists of axonal degeneration and neuronal plasticity secondary to the initial vascular damage. This case series describes four cases of poststroke dystonias. Although clinical and radiological findings suggest their cause–effect relationship, we have performed genetic testing using clinical exome sequencing to rule out incidental co-occurrence of genetic dystonic syndrome in a patient with stroke. We have documented the clinical evolution of the dystonic features and attempted clinico-radiological correlations using magnetic resonance imaging. A video document of all the cases is provided, highlighting the clinical distribution of the dystonic features and unusual findings. Treatment aspects are briefly discussed.

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Recently it has become increasingly apparent that neurobiological processes can be modified by the bidirectional communication occurring along the brain–gut axis. The microbiota play an important role in this communication through different routes in both physiological and pathological conditions. Gut microbia constitute approximately 100 trillion diverse array of microbes—around 1000 species having greater than 7000 strains—which includes bacteria, yeast, helminthes, protozoa, and viruses. They outnumber human cells and are 150 times the human genes. Most bacteria live in large intestine. There are different causes for the possible gut and Parkinson’s disease (PD) link. Gut is the entry point of many environmental toxins such as pesticides. Pathological deposition of alpha-synuclein starts in the gut several years before the onset of Parkinson symptoms. Constipation is reported as one of the earliest symptoms of PD (4–5 years). Alpha-synuclein is the protein expressed normally in the enteric nervous system (ENS). The level increases by age, but patients with PD have much higher level and early appearance of alpha-synuclein aggregation. Patients with PD show an increased intestinal permeability than the controls due to the defects in intestinal tight junctions. The phenotype is consistent with low-grade intestinal inflammation. Pro-inflammatory immune activity increases the level of alpha-synuclein in gut. Alpha-synuclein can migrate through vagus. It can also enter through circulation into the brain through disrupted blood–brain barrier. Systemic inflammation itself can modify alpha-synuclein in central nervous system. Several strategies are used to prove the gut–brain connection, which could in future be a potential therapeutic option in PD. These include influence of the gut microbiota on brain (viz, germ-free/gnotobiotic animals), use of oral antibiotics (e.g., minocycline, ampicillin to alter gut flora), use of probiotics, and fecal microbiota transplantation.

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