Epidemiology of Motoric Cognitive Risk Syndrome in the Kerala Einstein Study: Protocol for a Prospective Cohort Study.

BACKGROUND: The southern India state of Kerala has among the highest proportion of older adults in its population in the country. An increase in chronic age-related diseases such as dementia is expected in the older Kerala population. Identifying older individuals early in the course of cognitive decline offers the best hope of introducing preventive measures early and planning management. However, the epidemiology and pathogenesis of predementia syndromes at the early stages of cognitive decline in older adults are not well established in India. OBJECTIVE: The Kerala Einstein Study (KES) is a community-based cohort study that was established in 2008 and is based in the Kozhikode district in Kerala state. KES aims to establish risk factors and brain substrates of motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by the presence of slow gait and subjective cognitive concerns in individuals without dementia or disability. This protocol describes the study design and procedures for this KES project. METHODS: KES is proposing to enroll a sample of 1000 adults ≥60 years old from urban and rural areas in the Kozhikode district of Kerala state: 200 recruited in the previous phase of KES and 800 new participants to be recruited in this project. MCR is the cognitive phenotype of primary interest. The associations between previously established risk factors for dementia as well as novel risk factors (apathy and traumatic brain injury) and MCR will be examined in KES. Risk factor profiles for MCR will be compared between urban and rural residents as well as with individuals who meet the criteria for mild cognitive impairment (MCI). Cognitive and physical function, medical history and medications, sociodemographic characteristics, lifestyle patterns, and activities of daily living will be evaluated. Participants will also undergo magnetic resonance imaging and electrocardiogram investigations. Longitudinal follow-up is planned in a subset of participants as a prelude to future longitudinal studies. RESULTS: KES (2R01AG039330-07) was funded by the US National Institutes of Health in September 2019 and received approval from the Indian Medical Council of Research to start the study in June 2021. We had recruited 433 new participants from urban and rural sites in Kozhikode as of May 2023: 41.1% (178/433) women, 67.7% (293/433) rural residents, and 13.4% (58/433) MCR cases. Enrollment is actively ongoing at all the KES recruitment sites. CONCLUSIONS: KES will provide new insights into risk factors and brain substrates associated with MCR in India and will help guide future development of regionally specific preventive interventions for dementia. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49933.

Skin biopsy as an aid to diagnosis of disorders of the nervous system without cutaneous manifestations.

There are several neurological diseases wherein skin biopsy is useful for diagnosis, even in the absence of skin involvement. Skin biopsy is especially relevant in diseases in which the metabolic error is unknown or has no available diagnostic biochemical test. Skin biopsy, being relatively noninvasive, obviates the need for an invasive procedure such as a brain biopsy. These disorders wherein skin biopsies are particularly useful include the progressive myoclonic epilepsies, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), neuroaxonal dystrophy, and small fiber neuropathies (SFN). We review the role of skin biopsy in such conditions with notes on preferred sites and techniques.

Mobile App Based Strategy Improves Door-to-Needle Time in the Treatment of Acute Ischemic Stroke.

BACKGROUND: Time to revascularization is critical in improving outcomes in stroke thrombolysis. We studied the effectiveness of a mobile app based strategy to improve door-to-needle time (DNT) in treatment of acute ischemic stroke. METHODS: Consecutive patients presenting with acute ischemic stroke to the emergency department at a tertiary care hospital in Southern India between April 2017 - September 2018 were included. The app enabled rapid entry of patient parameters, the NIH stroke scale (NIHSS), thrombolysis checklist and dose calculation along with team synchronization, notifying all on-call members and team leaders of the patient movement, and sharing of radiological images. DNT captured from the app was compared to previous values from our center using one-way Analysis of Variance (ANOVA) after adjusting for differences in baseline variables. RESULTS: A total of 76 patients were thrombolysed during the study period, while using the mobile app. The mean DNT was 41 min, with 89% being thrombolysed within 60 min and 57% being thrombolysed within 45 min. Compared to 100 consecutive patients thrombolysed in the months prior to April 2017 where the mean DNT was 57 min, with 67% thrombolysed within 60 min and 47% being thrombolysed within 45 min, there was a mean DNT decrease of 16 min with 1.3x increase in DNT < 60 min. This difference was statistically significant after adjusting for age, sex and NIHSS Score (p=0.005, One-Way ANOVA). CONCLUSION: We have been able to demonstrate a significant improvement in DNT using mobile app as a tool to improve team performance.

Epidural blood patch for spontaneous intracranial hypotension.

A 32-year-old woman presented to the neurology department with complaints of holocranial headache of 1-month duration, which was getting worse on sitting up and standing. Headache was not relieved with analgesics but on lying down. A provisional diagnosis of spontaneous intracranial hypotension was considered, which was confirmed by the findings on magnetic resonance imaging. She was given an epidural blood patch, which relieved her symptoms.

Magnetic resonance imaging findings in brain resulting from high-voltage electrical shock injury of the scalp.

We report a case of high-voltage electrical injury to scalp, focusing on the magnetic resonance imaging (MRI) findings in brain. A 51-year-old male suffered burns to the right side of scalp and loss of consciousness following electric shock. Brain abnormalities were detected on MRI taken 4 days after the insult. Right parietal lobe neuroparenchyma beneath the scalp burn defect demonstrated homogeneous hypointensity on T1-weighted MR images, while T2-weighted images depicted hyperintensity mainly in white matter forming finger-like projections. Follow-up MRI showed that the abnormality had disappeared, indicating that the cerebral edema was reversible.

Histology of Thrombectomy Specimen Reveals Cardiac Tumor Embolus in Cryptogenic Young Stroke.

A 25-year-old woman presented with acute onset of right hemiplegia and global aphasia with National Institutes of Health Stroke Scale score of 19. Computed tomography angiography demonstrated occlusion of the left proximal middle cerebral artery. She was thrombolysed with intravenous recombinant tissue plasminogen activator (0.6 mg/kg) within 3 hours of onset of symptoms and was taken up for mechanical thrombectomy. The retrieved specimen appeared pale white and soft; histopathologic examination revealed a papillary neoplasm composed of papillae with hyalinized cores lined by endothelium, consistent with papillary fibroelastoma of cardiac origin. Transesophageal echocardiography showed no abnormalities, which can be explained by complete embolization of the mass into the cerebral circulation. On follow-up after 5 months, the patient recovered with only minimal aphasia and no cardiac symptoms. Our experience with this case highlights the importance of histopathologic examination of the mechanical thrombectomy specimen, as it provided the only clue to the etiology of stroke.

Cerebral Small Vessel Disease and Motoric Cognitive Risk Syndrome: Results from the Kerala-Einstein Study.

BACKGROUND: The contribution of cerebral small vessel disease to cognitive decline, especially in non-Caucasian populations, is not well established. OBJECTIVE: We examined the relationship between cerebral small vessel disease and motoric cognitive risk syndrome (MCR), a recently described pre-dementia syndrome, in Indian seniors. METHODS: 139 participants (mean age 66.6 ± 5.4 y, 33.1% female) participating in the Kerala-Einstein study in Southern India were examined in a cross-sectional study. The presence of cerebral small vessel disease (lacunar infarcts and cerebral microbleeds (CMB)) and white matter hyperintensities on MRI was ascertained by raters blinded to clinical information. MCR was defined by the presence of cognitive complaints and slow gait in older adults without dementia or mobility disability. RESULTS: Thirty-eight (27.3%) participants met MCR criteria. The overall prevalence of lacunar infarcts and CMB was 49.6% and 9.4% , respectively. Lacunar infarcts in the frontal lobe, but no other brain regions, were associated with MCR even after adjusting for vascular risk factors and presence of white matter hyperintensities (adjusted Odds Ratio (aOR): 4.67, 95% CI: 1.69-12.94). Frontal lacunar infarcts were associated with slow gait (aOR: 3.98, 95% CI: 1.46-10.79) and poor performance on memory test (ß: -1.24, 95% CI: -2.42 to -0.05), but not with cognitive complaints or non-memory tests. No association of CMB was found with MCR, individual MCR criterion or cognitive tests. CONCLUSIONS: Frontal lacunar infarcts are associated with MCR in Indian seniors, perhaps, by contributing to slow gait and poor memory function.

Motoric cognitive risk syndrome: multicountry prevalence and dementia risk.

OBJECTIVES: Our objective is to report prevalence of motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints, in multiple countries, and its association with dementia risk. METHODS: Pooled MCR prevalence analysis of individual data from 26,802 adults without dementia and disability aged 60 years and older from 22 cohorts from 17 countries. We also examined risk of incident cognitive impairment (Mini-Mental State Examination decline ≥4 points) and dementia associated with MCR in 4,812 individuals without dementia with baseline Mini-Mental State Examination scores ≥25 from 4 prospective cohort studies using Cox models adjusted for potential confounders. RESULTS: At baseline, 2,808 of the 26,802 participants met MCR criteria. Pooled MCR prevalence was 9.7% (95% confidence interval [CI] 8.2%-11.2%). MCR prevalence was higher with older age but there were no sex differences. MCR predicted risk of developing incident cognitive impairment in the pooled sample (adjusted hazard ratio [aHR] 2.0, 95% CI 1.7-2.4); aHRs were 1.5 to 2.7 in the individual cohorts. MCR also predicted dementia in the pooled sample (aHR 1.9, 95% CI 1.5-2.3). The results persisted even after excluding participants with possible cognitive impairment, accounting for early dementia, and diagnostic overlap with other predementia syndromes. CONCLUSION: MCR is common in older adults, and is a strong and early risk factor for cognitive decline. This clinical approach can be easily applied to identify high-risk seniors in a wide variety of settings.

Intravenous thrombolysis for acute ischemic stroke in the 3- to 4·5-hour window--the Malabar experience.

BACKGROUND: Intravenous thrombolysis for acute ischemic stroke with recombinant tissue plasminogen activator has been shown to be beneficial up to 4.5-hours of symptom onset. AIMS: The study aims to review our experience with thrombolysis with recombinant tissue plasminogen activator in the 3- to 4.5-hours window in acute ischemic stroke. SETTINGS AND DESIGN: Prospective observational study of patients with acute ischemic stroke thombolysed between 3- and 4.5-hours after onset from July 2009 to October 2012 at a tertiary-care center in the Malabar region of South India. MATERIALS AND METHODS: The dose of recombinant tissue plasminogen activator used was 50 mg in all patients. Inclusion and exclusion criteria were similar to European Co-operative Acute Stroke Study-3 criteria, with the exceptions that we did not use an age cutoff of 80 years and did not restrict thrombolysis for previous stroke with diabetes or elevated blood glucose levels. STATISTICAL ANALYSIS USED: Good outcome was defined as a three-month modified Rankin Score of 2 or less. The chi-square test was used to compare the outcome among various sub-types of ischemic stroke. The age, blood glucose, National Institute of Health Stroke Scale Score, and time to thrombolysis were compared between groups with the nonparametric Mann-Whitney U-test. RESULTS: Thirty-one patients (median age 65 years, range 44-85, and median National Institute of Health Stroke Scale Score 10, range 5-22) were thrombolysed in the 3- to 4.5-hours window after stroke onset during the study period. In the first 24 h, 16 patients (52%) improved in National Institute of Health Stroke Scale Score by 4 or more points while three worsened by 4 or more points. At the three-month follow up, 15 patients (48%) were functionally independent (modified Rankin Score ≤ 2). None had symptomatic intracerebral hemorrhage. There was no significant difference in outcome between the various ischemic stroke sub-types. The baseline age, National Institute of Health Stroke Scale Score, blood glucose, and onset to treatment time did not differ significantly between the groups with good and poor outcome. CONCLUSION: Our initial experience confirms that thrombolysis for ischemic stroke in the extended window is safe and beneficial.

Picture-based memory impairment screen for dementia.

OBJECTIVES: To develop and validate a picture-based memory impairment screen (PMIS) for the detection of dementia. DESIGN: Cross-sectional. SETTING: Outpatient clinics, Baby Memorial Hospital, Kozhikode city in the southern Indian state of Kerala. PARTICIPANTS: Three hundred four community-residing adults aged 55 to 94 with a mean education level of 8 years; 65 were diagnosed with dementia. MEASUREMENTS: PMIS: a culture-fair picture-based cognitive screen designed to be administered by nonspecialists. Diagnostic accuracy estimates (sensitivity, specificity, positive and negative predictive power) of PMIS cut-scores in detecting dementia (range 0-8). RESULTS: PMIS scores were worse in participants with dementia (1.5) than in controls (7.7, P < .001). At the optimal cut-score of 5, PMIS had a sensitivity of 95.4% (95% confidence interval (CI) = 90.3-100.0%) and a specificity of 99.2% (95% CI = 98.0-100.0%) for detecting dementia. In the 167 participants with <10 years of education, PMIS scores of five or less had a sensitivity of 97.8% (95% CI = 93.6-100.0%) and specificity of 99.2% (95% CI = 97.6-100.0%). The PMIS had better specificity than the Mini-Mental State Examination in detecting dementia, especially in older adults with low education. CONCLUSION: The PMIS is a brief and reliable screen for dementia in elderly populations with variable literacy rates.

Leukoencephalopathy with intracranial calcifications and cysts in an adult: Case report and review of literature.

Leukoencephalopathy, intracranial calcifications, and cysts (LCC) is a very rare cerebral disorder, first described in 3 children in 1996. It has subsequently been reported in adults and children from Europe and America, but has not so far been reported from Asia. We report an adult patient with pathologically proven LCC from a tertiary care hospital in South India. He presented with features of ataxia and raised intracranial pressure. Magnetic resonance imaging of the brain showed multiple bilateral cerebral cystic lesions along with diffuse white matter lesions in the cerebral and cerebellar white matter, and computed tomography of brain showed multiple calcifications in the white matter and basal ganglia. A large right cerebellar cyst causing mass effect was surgically excised. Histopathologic features were consistent with earlier reports of LCC and showed Rosenthal fibers, angiomatous changes, and calcifications. Our report suggests that although it is rare, LCC has a global distribution.

Gait and cognition in older adults: Insights from the Bronx and Kerala.

BACKGROUND: Recent reports indicate that gait dysfunction can occur early in the course of cognitive decline suggesting that motor and cognitive functions in older adults may share common underlying brain substrates, pathological processes, and risk factors. OBJECTIVE: This study was designed to report the association between gait and cognition in older adults in USA and the southern Indian state of Kerala. MATERIALS AND METHODS: Literature review of gait and cognition studies conducted in Bronx County, USA as well as preliminary results from the Kerala-Einstein study (Kozhikode city, Kerala). RESULTS: Review of published studies based in the Bronx shows that both clinical and quantitative gait dysfunction are common in older adults with cognitive impairment. Furthermore, clinical and quantitative gait dysfunction in cognitively normal older adults was a strong predictor of future cognitive decline and dementia. Our preliminary study in Kozhikode city shows that timed gait is slower in older adults diagnosed with dementia and mild cognitive impairment syndrome compared to healthy older controls. CONCLUSIONS: A strong association between gait and cognition is seen in seniors in USA as well as Kerala. A better understanding of the relationship between gait and cognition may help improve current diagnostic and therapeutic approaches globally.

Homocysteine, folate and vitamin B(12) in puerperal cerebral venous thrombosis.

BACKGROUND AND OBJECTIVE: Hyperhomocysteinemia (hyper-Hcy) is a known risk factor for venous thrombosis, but few studies document the risk in puerperal cerebral venous thrombosis (CVT). Nutritional folate and vitamin B(12) deficiency can cause hyper-Hcy and pregnancy may contribute to this deficiency. We studied the association of plasma total homocysteine (tHcy), folate and vitamin B(12) levels with puerperal CVT through a case-control study. METHODS: Sixty women with puerperal CVT and 64 healthy puerperal controls were recruited. Plasma fasting tHcy was estimated by high pressure liquid chromatography using coulometric electrochemical detection. Vitamin B(12) and folate were measured by radioimmunoassay. Risk of puerperal CVT was estimated for each of the three variables. RESULTS: Adjusted odds ratio for the risk of puerperal CVT with hyper-Hcy (>90th percentile) was 10.8 (95% CI: 4.0-29.4; adjusted for vitamin B(12) and folate levels). Low folate and vitamin B(12) levels (<10th percentile) did not increase the risk for puerperal CVT. There was a significant inverse correlation between folate and tHcy levels (rho=-0.471, p<0.001). CONCLUSIONS: Hyperhomocysteinemia is associated with an increased risk of puerperal CVT occurring in Indian women and low folate levels contribute significantly to hyper-Hcy. Regular antenatal folate and vitamin B(12) supplementation is likely to lower puerperal tHcy levels, but its clinical benefit needs to be tested by large therapeutic trials.

Primary cardiac cytotoxic T-cell lymphoma presenting with neurological deficits: a case report.

BACKGROUND: Primary cardiac lymphoma is extremely rare in immunocompetent patients. Clinical manifestations vary, and, most often, diagnosis is not made until autopsy. The majority of reported primary cardiac lymphoma cases have been of B-cell origin, while T-cell cardiac lymphomas have been extremely rare. Occasionally, lymphomas and other systemic malignancies clinically present as paraneoplastic neurological syndromes. METHODS: We report a unique case of primary cardiac peripheral T-cell lymphoma of cytotoxic phenotype, clinically presenting with neurological features of external ophthalmoplegia and lower cranial nerve paresis mimicking mitochondrial cytopathy, that was recognized at autopsy. Brain and thoracoabdominal viscera retrieved at autopsy were fixed in 10% buffered formalin and processed for paraffin embedding. In addition to routine histology, immunohistochemistry for immunophenotypic characterization of lymphoma cells was performed. Fresh skeletal muscle was processed for cryosectioning and histochemical staining. RESULTS: On gross examination, the heart showed multiple circumscribed, whitish nodules on both sides. Histological examination of these nodules revealed lymphomatous deposits-cells expressing CD45, CD2, CD3, CD5, CD7, CD8, perforin, and granzyme B. Histological sections from the brain showed foci of demyelination and patchy perivascular lymphoid cell aggregates in leptomeninges and within the parenchyma. These lymphoid cells expressed CD2, CD3, and CD5, with the T cells being predominantly CD4 (CD4:CD8>2), which was unlike the CD8-predominant lymphomatous infiltrate in the heart. Hence, these lymphoid cells in the brain, rather than disseminated lymphoma cells, were considered to be related to the demyelinating process. There was no evidence of lymphomatous deposits in the rest of the viscera examined. CONCLUSION: A diagnosis of primary cardiac peripheral T-cell lymphoma of cytotoxic phenotype clinically manifesting as paraneoplastic demyelinating lesions in the brain was described.

Cirrhosis presenting as Parkinsonism.

Cirrhosis presenting as Parkinsonism is a distinct subset of acquired chronic hepatocerebral degeneration. The entity is not rare, and unless suspected, cirrhosis can easily be overlooked. We report our experience with three such patients. They presented to us, over a period of two years, with symmetrical Parkinsonism and were later diagnosed to have cirrhosis with portal hypertension. All patients had minimal or absent tremors. Reversal of serum albumin to globulin ratio and evidence of cirrhosis on abdominal ultrasound were consistent. All three patients had the characteristic MRI abnormality of symmetrical T1 hyperintensity in basal ganglia and anterior midbrain. They improved to variable extents after treatment for cirrhosis, along with dopa agonists. We stress the importance of recognizing this syndrome and briefly review the relevant literature.

Stroke with supernumerary phantom limb: case study, review of literature and pathogenesis.

OBJECTIVE: Constitute hypothesis for origin of supernumerary phantom limb (SPL) after stroke. METHOD: Single case description, review of literature and formulation of hypothesis. RESULTS: A 59-year-old lady was evaluated for complaints of left-sided hemiparesis and extra limbs attached to her left shoulder for the past 7 months. Neuropsychological assessment revealed left hemineglect with SPL, and profile suggested bilateral frontal, right parietotemporal and basal ganglia involvement. Magnetic resonance imaging brain scan showed gliotic cavity secondary to the old haematoma in right putamen with white matter changes in the right frontoparietotemporal lobes. CONCLUSIONS: The conceptual framework of body schema can be used to classify many of the neurological disorders of body representation. Generation of SPL comes under the subtype of pathology of updating among the disorders of body schema. The continuous updating allows the body schema to modulate perceptual processing of objects according to their position in space. Brain areas classified as parts of motor system can, under pathological conditions (haemorrhage), influence body perception. So, when she used to move her arm, the representation of the estimated position was not updated by the motor commands. Sensory and motor information therefore becomes discrepant, and failure to integrate these two sources of information leads to loss of normal coherence, and the perceived shape of the body was altered by adding a SPL to accommodate the discrepancy.

Periodic lateralized epileptiform discharges in neurosyphilis.

We report two patients of neurosyphilis with periodic lateralized epileptiform discharges (PLEDs) in the EEG. Patient 1, a 32-yr-old man manifested with rapidly progressive cognitive decline and abnormal behavior and recurrent generalized tonic-clonic seizures. EEG revealed periodic epileptiform discharges arising from the anterior temporal and frontal region, predominantly from the right. Diffusion weighted MRI of brain did not show any focal restricted diffusion. Patient 2, a 33-yr-old woman presented with 2-year history of behavioral abnormalities, generalized tonic-clonic seizures and unconcerned urinary incontinence. EEG revealed PLEDS arising from the left anterior temporal region. Her CT scan showed gross cerebral atrophy. Both the patients improved partially with treatment and PLEDs resolved completely. PLEDs may be recorded in EEG of patients with neurosyphilis without imageological evidence of focal cerebral lesion.