Mohan Leslie Noone

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.

Homocysteine, folate and vitamin B12 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.

Picture-Based Memory Impairment Screen for Dementia

To develop and validate a picture‐based memory impairment screen (PMIS) for the detection of dementia.

Intravenous thrombolysis for acute ischemic stroke: The Malabar experience 2003 to 2008

We report the 5-year experience with thrombolysis in acute ischemic stroke from a tertiary care hospital in the Malabar region of South India. All stroke patients thrombolyzed with intravenous recombinant tissue plasminogen activator (rt-PA) from May 2003 to May 2008 were studied in an open, non-randomized, prospective study. Of 2,308 ischemic stroke patients admitted, 57 patients (2.5%) were thrombolyzed with rt-PA (age range, 35-78 years: 40 males, 17 females). The time from presentation at the hospital to initiation of thrombolysis ranged from 15 to 120 minutes (median 50 minutes). The dose of rt-PA used was from 0.6 mg/kg to 0.9 mg/kg. At 3 months 29 patients (51%) were functionally independent, with a modified Rankin scale score of 2 or less. Seven patients (12%) died within 3 months; one had an intracerebral hemorrhage (1.7%). The benefit of treatment was seen in all stroke subtypes. We have been able to show that intravenous thrombolysis in acute ischemic stroke is safe, effective and feasible in our part of the world.

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.

Biotin-responsive basal ganglia disease: a treatable and reversible neurological disorder of childhood.

Biotin-responsive basal ganglia disease is a rare childhood neurological disorder of uncertain etiology that is treatable if suspected and diagnosed. Only few cases have been reported earlier in literature. We report a case of biotin-responsive basal ganglia disease suspected clinically, corroborated by neuroimaging and a dramatic response to biotin therapy.

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.

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

Summary:  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.

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.