Endovascular Treatment for Cerebral Venous Sinus Thrombosis: Comparison among Different Endovascular Procedures.

Background: Cerebral venous sinus thrombosis (CVST) is a rare, treatable cause of stroke. Even though CVST has an established medical treatment, 15% of patients remain refractory to treatment. These patients may be candidates for endovascular treatment (EVT), yet the selection of patients remains a challenge. The study aims to understand the profile and outcome of patients treated with EVT and the type of procedure associated with good outcomes. Methods: This is a single-center, retrospective analysis of CVST patients who underwent EVT from 2009 till 2022. Patients who received only medical management were excluded. Modified Rankin Scale (mRS) ≤2 at 3 months was taken as the primary outcome. Secondary outcomes assessed were hospital stay, death, recurrence, mRS ≤ 2 at discharge, and angiographic recanalization. Results: Fifty-two patients were included. Twenty-eight (53.8%) were males; the mean age was 33.3 ± 12.3 years. Headache (n = 44, 84.6%) predominated among the symptoms. The common risk factors were anemia (n = 13, 25.5%) and hyperhomocysteinemia (n = 13, 25.5%). Worsening of sensorium (n = 21, 40.3%) and non-improvement of symptoms (n = 15, 28.8%) were the common indications for the procedure. Twenty-five (48.1%) people underwent in situ thrombolysis (IST). Death occurred in eight (15.3%) patients. Thirty-six (73.5%; 36/49) patients had a good outcome at 3 months. IST had a significantly better outcome (mRS ≤ 2, n = 20, 80%) compared to other procedures (P = 0.04). Hospital stay was lesser in the IST subgroup, but without statistical significance. Midline shift >5 mm (odds ratio [OR] 6.8 [1.5-30.9], P = 0.01) and Glasgow Coma Scale <9 before the procedure (OR 27.2 [3.1-236.4], P = 0.002) predicted bad outcomes at 3 months. Female gender (OR 4.5 [1.07-8.8], P = 0.03), presence of altered sensorium (OR 10.2 [1.2-87.5], P = 0.01), encephalopathic syndrome (P = 0.02), presence of parenchymal bleed (OR 3.7 [0.9-4.5], P = 0.04), and midline shift (OR 4.8 [1.1-20.2], P = 0.03) were associated with poor outcome at discharge. Conclusion: EVT yielded good outcomes in carefully selected, medically refractory patients of CVST. IST performed well compared to other procedures.

Endovascular Therapy in Large Core Ischemic Strokes: Real-World Indian Experience.

BACKGROUND: Large core acute ischemic strokes have predominantly been excluded from endovascular therapy (EVT) studies due to perceived higher risks of hemorrhage and poorer functional outcomes. However, recent randomized controlled trials (RCTs) indicate that EVT for large vessel occlusion (LVO) strokes improves functional outcomes compared to medical management alone, despite higher hemorrhagic transformation rates, with no corresponding increase in symptomatic intracerebral hemorrhage (sICH) rates. The real-world outcomes of this intervention in Indian patients remain underexplored. OBJECTIVES: To evaluate the real-world outcomes of EVT for large core acute ischemic strokes with LVO in an Indian population. METHODS: We conducted a single-center, retrospective observational study using a 7 years prospective database of EVT in anterior circulation stroke patients. Patients with Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 3-5 were included. Clinical and radiologic data were analyzed, with the primary endpoint being 90-day modified Rankin scale (mRS) scores. Safety outcomes included rates of sICH and mortality. Descriptive statistical analysis was done using Microsoft Excel. RESULTS: The study included 25 patients who met the inclusion criteria. Mean age of patients was 52.9 ± 14.3 years, and there were 13 (52%) males. Median ASPECTS was 5 (interquartile range 4-5). Successful recanalization, classified by modified Thrombolysis in Cerebral Infarction score, was 92%. Good functional recovery, that is, 90-day mRS 0-3, was achieved in nine (36%) patients. Safety outcomes: sICH was seen in four (16%) and mortality was reported in nine (36%) patients. CONCLUSIONS: Our results reaffirm findings from RCTs, provide updated real-world evidence, and suggest that EVT is a viable option to be considered in selected patients with large core ischemic infarcts.

Calcific Miliary Brain Metastasis in Adenocarcinoma Lung Treated with Gefitinib.

Calcific miliary brain metastasis is an extremely rare form of brain secondaries. A 52-year-old man diagnosed with lung adenocarcinoma, on oncotherapy with gefitinib had a partial initial response to treatment. Later he was readmitted with seizures and cognitive dysfunction. His initial brain computed tomography (CT) and magnetic resonance imaging (MRI) were normal. However, his later CT images revealed multiple small calcified lesions over both hemispheres and contrast MRI revealed scattered tiny miliary nodules enhanced by gadolinium over bilateral cerebral, cerebellar hemispheres, thalami, and basal ganglia with foci of hypointensity in susceptibility-weighted images (SWI) and phase imaging suggesting calcification. A diagnosis of calcific miliary brain metastasis was made. Miliary calcification as an initial presentation of brain metastases in patients with lung cancer is uncommon. Use of oral tyrosine kinase inhibitor like gefitinib increases the likelihood development of calcific brain metastases due to the prolonged survival time contributed by its use.

Efficacy of Caffeine in ADCY5-Related Dyskinesia: A Retrospective Study.

BACKGROUND: ADCY5-related dyskinesia is characterized by early-onset movement disorders. There is currently no validated treatment, but anecdotal clinical reports and biological hypotheses suggest efficacy of caffeine. OBJECTIVE: The aim is to obtain further insight into the efficacy and safety of caffeine in patients with ADCY5-related dyskinesia. METHODS: A retrospective study was conducted worldwide in 30 patients with a proven ADCY5 mutation who had tried or were taking caffeine for dyskinesia. Disease characteristics and treatment responses were assessed through a questionnaire. RESULTS: Caffeine was overall well tolerated, even in children, and 87% of patients reported a clear improvement. Caffeine reduced the frequency and duration of paroxysmal movement disorders but also improved baseline movement disorders and some other motor and nonmotor features, with consistent quality-of-life improvement. Three patients reported worsening. CONCLUSION: Our findings suggest that caffeine should be considered as a first-line therapeutic option in ADCY5-related dyskinesia. © 2022 International Parkinson and Movement Disorder Society.

Apraxia of Lid Opening in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease-Frequency, Risk Factors and Response to Treatment.

BACKGROUND: New-onset apraxia of lid opening (ALO) is reported to occur in Parkinson's disease (PD) patients following Deep Brain Stimulation (DBS). There are only few systematic studies on this uncommon disorder of eyelid movements. OBJECTIVES: We aimed to examine the frequency, temporal evolution, predisposing factors and response to treatment, of new-onset ALO in PD patients who underwent bilateral subthalamic nucleus (STN) DBS. METHODS: We retrospectively reviewed the data of patients who underwent STN DBS at our centre between 1999 and 2017, with a minimum of 2 years of follow up after surgery. RESULTS: New-onset ALO was seen in 17 (9.1%) of the 187 patients after an average of 16.9 months (Range - 6-36 months). Comparison of the groups with and without ALO revealed that ALO occurred more often in older patients, both at the onset of PD symptoms and at surgery and in those with non-tremor dominant subtypes of PD and freezing of gait at baseline. The extent of levodopa dose reduction after surgery and the pre-operative severity of motor symptoms were not risk factors. Response to adjustments of dopaminergic medications and stimulation parameters was ill-sustained or nil. Botulinum toxin therapy resulted in satisfactory improvement in the majority. CONCLUSIONS: New-onset ALO is an uncommon phenomenon that manifests months after STN DBS. Development of ALO is likely to be due to the effects of chronic stimulation of basal ganglia-thalamo-cortical or brain stem circuits controlling lid movements in susceptible patients. Botulinum toxin therapy offers relatively better relief of symptoms than other strategies.

Myoclonus-Ataxia Syndrome Associated with COVID-19.

Neurological manifestations of coronavirus disease (COVID-19) have increasingly been reported since the onset of the pandemic. Herein, we report a relatively new presentation. A patient in the convalescence period following a febrile illness with lower respiratory tract infection (fever, myalgia, nonproductive cough) presented with generalized disabling myoclonus, which is phenotypically suggestive of brainstem origin, along with additional truncal cerebellar ataxia. His neurology work-ups, such as brain MRI, electroencephalography, serum autoimmune and paraneoplastic antibody testing, were normal. His CT chest scan revealed right lower lung infiltrates, and serological and other laboratory testing did not show evidence of active infection. COVID-19 titers turned out to be strongly positive, suggestive of post-COVID-19 lung sequelae. He responded partially to antimyoclonic drugs and fully to a course of steroids, suggesting a para- or postinfectious immune-mediated pathophysiology. Myoclonusataxia syndrome appears to be a neurological manifestation of COVID-19 infection, and knowledge regarding this phenomenon should be increased among clinicians for better patient care in a pandemic situation.

Genetic Architecture of Parkinson's Disease in the Indian Population: Harnessing Genetic Diversity to Address Critical Gaps in Parkinson's Disease Research.

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our "hub-spoke" model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD.

Asymptomatic Hearing Impairment Frequently Occurs in Early-Onset Parkinson's Disease.

OBJECTIVE: Recent reports of hearing impairment in Parkinson's disease (PD) have suggested that auditory dysfunction could be a non-motor manifestation of PD. These reports were based on observations of elderly patients for whom presbycusis may, to some extent, have contributed to hearing dysfunction. Therefore, we aimed to explore the auditory functions in younger patients with PD. METHODS: We conducted a case-control study in a relatively younger (< 55 years of age at study time) population of PD patients and healthy volunteers to test whether auditory dysfunction is a significant non-motor dysfunction in PD. Pure tone audiometry (PTA) and brainstem evoked response audiometry (BERA) were performed in all participants. RESULTS: None of the patients or controls reported hearing deficits. Fifty-one patients with PD and 50 healthy volunteers who were age- and gender-matched to the patients participated. PTA-detected hearing impairment was found in 64.7% of patients and 28% of controls (p < 0.001) for both low-mid and/or high frequencies. Hearing impairment was more frequent in the younger subgroups of patients than age-matched controls, while the frequency of hearing impairment was similar in older groups of subjects. BERA was not different between patients and controls. CONCLUSION: Asymptomatic auditory dysfunction is a common non-motor manifestation of early-onset PD and more frequent in younger patients, indicating that it may be independent of aging. The mechanism underlying this dysfunction appears to be peripheral, although a central dysfunction cannot be ruled out based on the findings of this study.

Deep brain stimulation for movement disorders.

Deep Brain Stimulation (DBS) was introduced into clinical practice nearly four decades ago and is currently the standard of care for patients with Parkinson's disease experiencing motor complications. Apart from this, it has several other established and emerging applications in movement disorders. The exact mechanisms by which DBS provides relief in movement disorders are still unclear; disruption of pathological neuronal synchrony and abnormal information flow through the neuronal circuits involved, are the most likely underlying mechanisms. DBS has been established to be a relatively safe procedure if patients are carefully selected and followed up by experienced multidisciplinary teams. Alternatives to the traditional stereotactic frame based techniques of lead implantation are emerging, and these, along with the other recent technological advances, are likely to extend the availability of this therapy to an increasing number of patients in the future.