Deep Brain Stimulation for Parkinson's Disease-the Developing World's Perspective.

Background: Deep brain stimulation (DBS) is the most widely used device-assisted therapy in patients with moderately advanced stages of Parkinson's disease (PD) experiencing motor complications. Only a minority of eligible patients get the opportunity to undergo DBS in the developing world. Objectives: To examine the proportion and characteristics of patients with motor complications of PD who are willing for DBS and who undergo surgery. Methods: Patients with motor complications of PD eligible for DBS over a five-year study period (2016-2020) were included. The demographic, clinical and socio-economic characteristics and information on their status in 2021 were collected and analyzed. Results: Among 1017 patients, 223 had motor symptoms qualifying for DBS and follow-up information available. Only 78 (35%) opted for surgery. The willing patients had higher socioeconomic status, were older and had longer duration of PD and motor complications, more freezing of gait, cognitive symptoms, and neuropsychiatric disturbances. 37 of them were found unfit during pre-operative work-up; only 41 (18%) with motor complications were finally taken up for DBS. Age, duration or severity of motor symptoms did not differ between patients who were finally selected for surgery and those who were not. Conclusions: Less than one-fifth of our patients with motor complications of PD finally underwent DBS. The patients appeared to wait till the late stages of PD, before making a decision on availing surgical treatment. The delay resulted in nearly half of them being found unfit in pre-operative work-up. Our findings may enable clinicians to counsel eligible patients more efficiently.

Parkinson's disease - genetic cause.

PURPOSE OF REVIEW: Our knowledge of the genetic architecture underlying Parkinson's disease has vastly improved in the past quarter century. About 5-10% of all patients suffer from a monogenic form of Parkinson's disease. RECENT FINDINGS: Mutations in autosomal dominant genes (e.g. SNCA, LRRK2, VPS35) or autosomal recessive genes (e.g. PRKN, PINK1, DJ-1) can cause genetic Parkinson's disease. Recessive DNAJC6 mutations can present predominantly as atypical parkinsonism, but also rarely as typical Parkinson's disease. Majority of Parkinson's disease is genetically complex. Mutation in RIC3 , a chaperone of neuronal nicotinic acetylcholine receptor subunit α-7 (CHRNA7), provides strong evidence for the role of cholinergic pathway, for the first time, in cause of Parkinson's disease. X-linked parkinsonism manifests at a young age accompanied by many (atypical) features such as intellectual disability, spasticity, seizures, myoclonus, dystonia, and have poor response to levodopa. SUMMARY: This review article aims to provide a comprehensive overview on Parkinson's disease genetics. MAPT , which encodes the microtubule associated protein tau, TMEM230, LRP10, NUS1 and ARSA are the five new putative disease-causing genes in Parkinson's disease. The validation of novel genes and its association with Parkinson's disease remains extremely challenging, as genetically affected families are sparse and globally widespread. In the near future, genetic discoveries in Parkinson's disease will influence our ability to predict and prognosticate the disease, help in defining etiological subtypes that are critical in implementation of precision medicine.

Pearls & Oy-sters: SCA21 Due to TMEM240 Variation Presenting as Myoclonus Dystonia Syndrome.

Spinocerebellar ataxia 21 due to TMEM240 disease-associated variation characteristically presents insidiously with a delay in language, motor, and social skill acquisition. The condition typically progresses to severe cognitive impairment. We report a patient with SCA21 who presented with myoclonus dystonia (M-D) syndrome and whose dystonia showed a modest response to levodopa. Affected family members (mother and sibling of the proband) also had a similar phenotype. Neuropsychology evaluation of the proband and afflicted family members revealed moderate impairments in attention, executive function, short-term and episodic memory, and marked impairments in planning, abstract reasoning, language, and visuospatial functions. Normal EEG, α-fetoprotein levels, and somatosensory evoked potentials helped to delineate SCA21 from other differential diagnoses. Motor impairment, pyramidal signs, and sensory impairment are usually absent in SCA21. This case highlights the importance of genetic testing in patients with M-D syndrome and supports a trial of levodopa for patients with dystonia from SCA21 due to TMEM240 variation.

Utility of Serial Nerve Conduction Studies in the Electrodiagnosis of Guillain-Barre Syndrome.

BACKGROUND: Guillain-Barre syndrome can be electrophysiologically classified into demyelinating and axonal subtypes and nerve conduction studies remain the mainstay in electrodiagnosis. Accurate electrodiagnosis has both therapeutic and prognostic significance and different criteria sets have been proposed for classification. OBJECTIVES: To electrophysiologically classify GBS patients into AIDP and axonal subtypes according to various published criteria (Cornblath, 1990: Hadden, 1998, Rajabally, 2015), investigate if serial NCS changes the classification, and to identify additional parameters which may support the electrodiagnosis. MATERIALS AND METHODS: In a retrospective study, we included all patients aged 15 to 80 years, admitted with a diagnosis of GBS between August 2015 and July 2017, who had at least two serial NCS. The various published criteria were applied to the two serial NCS and subtype classification along with diagnostic shifts on serial NCS were ascertained. RESULTS: At the first test, the established criteria gave a yield of 45.2% to 71% for AIDP, while 29% to 54.8% of patients were classified as axonal GBS. In the second study, there was a change in electrodiagnosis, ranging from 9.6% to 16.1%. The resolution of reversible conduction failure and misclassification of subtypes were the major reason for diagnostic shifts. Sural sparing pattern, facial nerve dysfunction, abnormal blink reflex, and phrenic nerve dysfunction were more common in AIDP. CONCLUSIONS: Serial nerve conduction studies allow an accurate electrodiagnosis of GBS subtypes, which has both therapeutic and prognostic implications. Also, the use of additional parameters such as blink reflex facial and phrenic nerve conduction may supplement routine NCS.

Clinical Spectrum, Therapeutic Outcomes and Prognostic predictors in Paraneoplastic Neurological Syndromes - Experiences from a Tertiary Care Center in India.

BACKGROUND: Paraneoplastic Neurological Syndromes (PNSs) are a heterogeneous group of immune-mediated disorders that often precede tumor diagnosis. There are few systematic studies on the spectrum and follow-up of PNSs. OBJECTIVE: To analyze the clinical spectrum, associated tumors, antibody profile, outcomes, and prognostic predictors in a cohort of PNSs admitted in a tertiary care center. METHODS: This retrospective study included 97 patients (2008-2019). PNSs were further classified as "classical," "nonclassical," "definite," and "possible." Clinical profile, diagnostic strategies, therapeutic options, and predictors of outcomes were identified. RESULTS: The median age was 54 years (range 17-81). Thirty-nine (40.2%) had classical PNS, and 58 (59.8%) had nonclassical PNS, 74 (76.3%) had "Definite" PNS while 23 (23.7%) had "Possible" PNS. Cerebellar degeneration, peripheral neuropathy, and encephalopathy were the three most common neurological syndromes. Tumors were diagnosed in 66 (68%) patients; Lung cancer was the most common primary tumor. Antibodies were positive in 52 (53.6%). Anti-Yo antibody and anti-Ma2 antibody were the most common antibodies. The majority (57.7%) received immunotherapy in addition to definitive treatment for the tumor. A good outcome was seen in 53 (54.6%). Factors associated with good outcome were: early diagnosis, mRS <3 at presentation, absence of metastatic disease, and adjuvant immunotherapy. CONCLUSION: A high index of clinical suspicion is essential for early diagnosis and prompt management of PNS, especially the nonclassical syndromes. Multimodality diagnostic imaging techniques and antibody profiling play a crucial role in the diagnosis. A favorable prognosis can be expected with the judicious use of immunotherapy and definitive treatment of malignancy.

Utility of stimulus induced after discharges in the evaluation of peripheral nerve hyperexcitability: Old wine in a new bottle?

Limited literature is available on stimulus induced after discharges (SIAD) in patients with peripheral nerve hyperexcitability (PNH). The aim of the study was to examine the diagnostic utility of SIAD in the diagnosis and monitoring of primary PNH disorders. In this retrospective study, we studied 26 patients who were admitted with a diagnosis of primary PNH to the department of Neurology from January 2013 to April 2019. Their clinical profile, immunological characteristics were extracted from the database and nerve conduction studies were relooked for the presence of SIAD. 76% of patients in the primary PNH cohort had SIAD with 90% of them being voltage-gated potassium channel complex antibody positive; predominantly against contactin-associated protein-2 antigen and rest being paraneoplastic. There was also resolution of SIAD following treatment indicating reversible hyperexcitability. SIAD is a sensitive marker for Primary PNH syndrome with monitoring and diagnostic implications.

Clinical Spectrum and Outcome of Neurosarcoidosis: A Retrospective Cohort Study from a Teaching Hospital in India.

CONTEXT: Neurosarcoidosis (NS) is a chronic disease with a diverse clinical spectrum, therapeutic response, and outcome. There is scarce literature from our country regarding the same. AIMS: The aim of this study was to evaluate the clinical spectrum, therapeutic responses, and outcomes of NS in an Indian cohort. SETTINGS AND DESIGN: In a cross-sectional study, we included all patients with NS treated at a quaternary care teaching hospital in India from January 2007 to October 2019. SUBJECTS AND METHODS: Patients older than 18 years of age fulfilling the diagnostic criteria for NS from the Neurosarcoidosis Consortium Consensus Group were included in the study. The therapeutic response and the degree of disability at last follow-up were assessed. RESULTS: We identified 48 patients, among them 3 were categorized as having definite NS, 30 probable NS, and 15 possible NS. Cranial neuropathy was the most common presentation (47.9%), followed by myelopathy (25%). Systemic involvement was identified in 95.83% and mediastinal lymph nodes were the most common site. Clinical improvement was seen in 65.8% and disease stabilized in 28.9%, while 5.26% deteriorated. Fifty percent recovered without any residual disability, while 26.3% had minor and 23.7% had major residual sequelae. CONCLUSIONS: NS is a diverse illness, with a heterogeneous spectrum of clinical presentation, treatment response, and outcome. Cranial neuropathy is the most common presenting feature and has a good prognosis while myelopathy has an unfavorable prognosis. Meningeal and brain parenchymal disease is difficult to diagnose accurately unless systemic involvement is present. The diagnosis of NS should be clinically suspected in the appropriate clinical setting, the presence of systemic involvement should be investigated, and histologic confirmation should be attempted.