16 results on '"Wijesekera, L"'
Search Results
2. Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials
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van Eijk, Ruben P. A, Jones, Ashley R., Sproviero, William, Shatunov, Aleksey, Shaw, Pamela J., Leigh, P. Nigel, Young, Carolyn A., Shaw, Christopher E., Mora, Gabriele, Mandrioli, Jessica, Borghero, Giuseppe, Volanti, Paolo, Diekstra, Frank P., van Rheenen, Wouter, Verstraete, Esther, Eijkemans, Marinus J. C, Veldink, Jan H., Chio, Adriano, Al-Chalabi, Ammar, van den Berg, Leonard H., van Es, Michael A, For UKMND-LiCALS and LITALS Study Group: Allen C, Counsell C, Farrin A, Al-Chalabi A, Dickie B, Kelly J, Leigh PN, Murphy CL, Payan C, Reynolds G, Shaw P, Steen IN, Thornhill M, Waters J, Zajicek J, Shaw PJ, Young CA, Morrison KE, Dhariwal S, Hornabrook R, Savage L, Burn DJ, Khoo TK, Dougherty A, Wijesekera L, Ellis CM, Ali R, O'Hanlon K, Panicker J, Pate L, Ray P, Wyatt L, Copeland L, Ealing J, Hamdalla H, Leroi I, Murphy C, O'Keeffe F, Oughton E, Partington L, Paterson P, Rog D, Sathish A, Sexton D, Smith J, Vanek H, Dodds S, Williams TL, Clarke J, Eziefula C, Howard R, Orrell R, Sidle K, Sylvester R, Barrett W, Merritt C, Talbot K, Turner MR, Whatley C, Williams C, Williams J, Cosby C, Hanemann CO, Imam I, Phillips C, Timings L, Crawford SE, Hewamadduma C, Hibberd R, Hollinger H, McDermott C, Mills G, Rafiq M, Taylor A, Waines E, Walsh T, Addison-Jones R, Birt J, Hare M, Majid T, Tortelli R, D'Errico E, Bartolomei I, Barbarossa E, Depau B, Costantino E, D'Amico E, Uncini A, Manzoli C, Quatrale R, Sette E, Montanari E, Merello M, Zarcone D, Mascolo M, Vignolo M, Messina S, Morelli C, Marinou K, Papetti L, Lunetta C, Gorni K, De Cicco D, Pipia C, Sola P, Georgoulopoulou E, Sagnelli A, Tedeschi, Gioacchino, Oggioni G, Nasuelli N, D'Ascenzo C, Cima V, Aiello M, Rizzi R, Rinaldi E, Luigetti M, Conte A, Torzini A, Greco G, Mutani R, Fuda G, Tommasi MA, van Eijk, Ruben P. A, Jones, Ashley R., Sproviero, William, Shatunov, Aleksey, Shaw, Pamela J., Leigh, P. Nigel, Young, Carolyn A., Shaw, Christopher E., Mora, Gabriele, Mandrioli, Jessica, Borghero, Giuseppe, Volanti, Paolo, Diekstra, Frank P., van Rheenen, Wouter, Verstraete, Esther, Eijkemans, Marinus J. C, Veldink, Jan H., Chio, Adriano, Al-Chalabi, Ammar, van den Berg, Leonard H., van Es, Michael A, For UKMND-LiCALS and LITALS Study Group: Allen, C, Counsell, C, Farrin, A, Al-Chalabi, A, Dickie, B, Kelly, J, Leigh, Pn, Murphy, Cl, Payan, C, Reynolds, G, Shaw, P, Steen, In, Thornhill, M, Waters, J, Zajicek, J, Shaw, Pj, Young, Ca, Morrison, Ke, Dhariwal, S, Hornabrook, R, Savage, L, Burn, Dj, Khoo, Tk, Dougherty, A, Wijesekera, L, Ellis, Cm, Ali, R, O'Hanlon, K, Panicker, J, Pate, L, Ray, P, Wyatt, L, Copeland, L, Ealing, J, Hamdalla, H, Leroi, I, Murphy, C, O'Keeffe, F, Oughton, E, Partington, L, Paterson, P, Rog, D, Sathish, A, Sexton, D, Smith, J, Vanek, H, Dodds, S, Williams, Tl, Clarke, J, Eziefula, C, Howard, R, Orrell, R, Sidle, K, Sylvester, R, Barrett, W, Merritt, C, Talbot, K, Turner, Mr, Whatley, C, Williams, C, Williams, J, Cosby, C, Hanemann, Co, Imam, I, Phillips, C, Timings, L, Crawford, Se, Hewamadduma, C, Hibberd, R, Hollinger, H, Mcdermott, C, Mills, G, Rafiq, M, Taylor, A, Waines, E, Walsh, T, Addison-Jones, R, Birt, J, Hare, M, Majid, T, Tortelli, R, D'Errico, E, Bartolomei, I, Barbarossa, E, Depau, B, Costantino, E, D'Amico, E, Uncini, A, Manzoli, C, Quatrale, R, Sette, E, Montanari, E, Merello, M, Zarcone, D, Mascolo, M, Vignolo, M, Messina, S, Morelli, C, Marinou, K, Papetti, L, Lunetta, C, Gorni, K, De Cicco, D, Pipia, C, Sola, P, Georgoulopoulou, E, Sagnelli, A, Tedeschi, Gioacchino, Oggioni, G, Nasuelli, N, D'Ascenzo, C, Cima, V, Aiello, M, Rizzi, R, Rinaldi, E, Luigetti, M, Conte, A, Torzini, A, Greco, G, Mutani, R, Fuda, G, and Tommasi, Ma more...
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Oncology ,R853.C55 ,medicine.medical_specialty ,Genotype ,Neuroprotective Agent ,Clinical Neurology ,Nerve Tissue Proteins ,Review ,Amyotrophic Lateral Sclerosis ,C9orf72 Protein ,Lithium Carbonate ,Neuroprotective Agents ,Proportional Hazards Models ,Proteins ,Pharmacogenetics ,Randomized Controlled Trials as Topic ,Neurology (clinical) ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Journal Article ,030212 general & internal medicine ,Amyotrophic lateral sclerosis ,business.industry ,Protein ,Pharmacogenetic ,medicine.disease ,Clinical trial ,RC0346 ,Meta-analysis ,Nerve Tissue Protein ,Proportional Hazards Model ,business ,030217 neurology & neurosurgery ,Meta-Analysis ,Amyotrophic Lateral Sclerosi - Abstract
OBJECTIVE\ud \ud To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders.\ud \ud METHODS\ud \ud Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype.\ud \ud RESULTS\ud \ud Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3).\ud \ud CONCLUSIONS\ud \ud This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials. more...
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- 2017
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Catalog
3. Nutritional factors associated with survival following enteral tube feeding in patients with motor neurone disease
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Rio, A., Ellis, C., Shaw, C., Willey, E., Ampong, M. A., Wijesekera, L., Rittman, T., Leigh, Nigel P., Sidhu, P. S., and Al-Chalabi, A.
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- 2010
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4. Neurosarcoidosis presenting as ghost lesions in the CNS: a diagnostic dilemma
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Wijesekera L, Crocker M, Silber E, deSouza Rm, Chandler C, and Hampton T
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medicine.medical_specialty ,Stereotactic biopsy ,Sarcoidosis ,Fourth ventricle ,Dizziness ,Diagnosis, Differential ,Central Nervous System Diseases ,medicine ,Humans ,Past medical history ,medicine.diagnostic_test ,business.industry ,Headache ,Neurosarcoidosis ,Magnetic resonance imaging ,General Medicine ,Middle Aged ,medicine.disease ,Pronator drift ,Magnetic Resonance Imaging ,Gait Ataxia ,Female ,Radiology ,Headaches ,medicine.symptom ,business - Abstract
A 50-year-old woman presented with a short history of headaches and dizziness. One week earlier she noticed impaired right leg coordination and had fallen twice. She had no significant past medical history. Examination showed impaired right arm and leg coordination, mild pronator drift and gait ataxia with no other neurological deficits. A magnetic resonance imaging scan of the brain showed an intra-axial mass lesion centred on the right middle cerebellar peduncle with partial effacement of the fourth ventricle and an unusual, slightly nodular pattern of enhancement (Figure 1). A computed tomography scan of the chest demonstrated bilateral nodular hilar masses felt consistent with reactive lymphadenopathy. No single large mass was present. Brain magnetic resonance imaging was consistent with either a primary lesion or atypical metastasis. She commenced dexamethasone 4 mg four times per day and stereotactic biopsy was scheduled. The planning magnetic resonance imaging, 2 weeks later, demonstrated marked reduction in the lesion's size raising the possibility of CNS lymphoma. Surgery was cancelled. Lumbar puncture showed no abnormalities. The steroid dose was reduced as a result of cushingoid sequelae and to establish if the lesion would re-expand. Interval scans showed progressive reduction in mass size despite decreasing steroid doses. Partial signal normalization within the cerebellum with resolution of mass effect and enhancement was observed (Figure 2). Repeat computed tomography of the chest (Figure 3) showed new, small, peripheral, left and right upper lobe pulmonary lesions. Histology following open biopsy of the left-sided lesion showed noncoalescent non-necrotizing granulomata consistent with sarcoidosis. Six months later the patient remains symptom free on prednisolone 2.5 mg once per day. more...
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- 2008
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5. A proposed staging system for amyotrophic lateral sclerosis
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Roche, J. C., primary, Rojas-Garcia, R., additional, Scott, K. M., additional, Scotton, W., additional, Ellis, C. E., additional, Burman, R., additional, Wijesekera, L., additional, Turner, M. R., additional, Leigh, P. N., additional, Shaw, C. E., additional, and Al-Chalabi, A., additional more...
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- 2012
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6. The risk to relatives of patients with sporadic amyotrophic lateral sclerosis
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Hanby, M. F., primary, Scott, K. M., additional, Scotton, W., additional, Wijesekera, L., additional, Mole, T., additional, Ellis, C. E., additional, Nigel Leigh, P., additional, Shaw, C. E., additional, and Al-Chalabi, A., additional more...
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- 2011
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7. Natural history and clinical features of the flail arm and flail leg ALS variants
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Wijesekera, L. C., primary, Mathers, S., additional, Talman, P., additional, Galtrey, C., additional, Parkinson, M. H., additional, Ganesalingam, J., additional, Willey, E., additional, Ampong, M. A., additional, Ellis, C. M., additional, Shaw, C. E., additional, Al-Chalabi, A., additional, and Leigh, P. N., additional more...
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- 2009
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8. Neurosarcoidosis presenting as ghost lesions in the CNS: a diagnostic dilemma
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deSouza, RM, primary, Crocker, M, additional, Wijesekera, L, additional, Hampton, T, additional, Silber, E, additional, and Chandler, C, additional
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- 2008
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9. Multisystem pathology in McLeod syndrome.
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Schon KR, O'Donovan DG, Briggs M, Rowe JB, Wijesekera L, Chinnery PF, and van den Ameele J
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- Male, Humans, Middle Aged, Basal Ganglia pathology, Atrophy pathology, Neuroacanthocytosis genetics, Neuroacanthocytosis diagnosis, Neuroacanthocytosis pathology, Muscular Diseases pathology
- Abstract
We present a comprehensive characterization of clinical, neuropathological, and multisystem features of a man with genetically confirmed McLeod neuroacanthocytosis syndrome, including video and autopsy findings. A 61-year-old man presented with a movement disorder and behavioral change. Examination showed dystonic choreiform movements in all four limbs, reduced deep-tendon reflexes, and wide-based gait. He had oromandibular dyskinesia causing severe dysphagia. Elevated serum creatinine kinase (CK) was first noted in his thirties, but investigations, including muscle biopsy at that time, were inconclusive. Brain magnetic resonance imaging showed white matter volume loss, atrophic basal ganglia, and chronic small vessel ischemia. Despite raised CK, electromyography did not show myopathic changes. Exome gene panel testing was negative, but targeted genetic analysis revealed a hemizygous pathogenic variant in the XK gene c.895C > T p.(Gln299Ter), consistent with a diagnosis of McLeod syndrome. The patient died of sepsis, and autopsy showed astrocytic gliosis and atrophy of the basal ganglia, diffuse iron deposition in the putamen, and mild Alzheimer's pathology. Muscle pathology was indicative of mild chronic neurogenic atrophy without overt myopathic features. He had non-specific cardiomyopathy and splenomegaly. McLeod syndrome is an ultra-rare neurodegenerative disorder caused by X-linked recessive mutations in the XK gene. Diagnosis has management implications since patients are at risk of severe transfusion reactions and cardiac complications. When a clinical diagnosis is suspected, candidate genes should be interrogated rather than solely relying on exome panels., (© 2023 The Authors. Neuropathology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Neuropathology.) more...
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- 2024
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10. Machine learning and clinical neurophysiology.
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Ray J, Wijesekera L, and Cirstea S
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- Humans, Algorithms, Neurophysiology, Machine Learning
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Clinical neurophysiology constructs a wealth of dynamic information pertaining to the integrity and function of both central and peripheral nervous systems. As with many technological fields, there has been an explosion of data in neurophysiology over recent years, and this requires considerable analysis by experts. Computational algorithms and especially advances in machine learning (ML) have the ability to assist with this task and potentially reveal hidden insights. In this update article, we will provide a brief overview where such technology is being applied in clinical neurophysiology and possible future directions., (© 2022. Crown.) more...
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- 2022
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11. Healthcare professionals' views on the provision of gastrostomy and noninvasive ventilation to amyotrophic lateral sclerosis patients in England, Wales, and Northern Ireland.
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Ruffell TO, Martin NH, Janssen A, Wijesekera L, Knights C, Burman R, Oliver DJ, Al-Chalabi A, and Goldstein LH
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- Adult, Allied Health Personnel psychology, England, Female, Humans, Male, Northern Ireland, Palliative Care, Quality of Life, Surveys and Questionnaires, Wales, Amyotrophic Lateral Sclerosis complications, Attitude of Health Personnel, Gastrostomy statistics & numerical data, Noninvasive Ventilation statistics & numerical data, Practice Patterns, Physicians' statistics & numerical data
- Abstract
Gastrostomy and noninvasive ventilation (NIV) are recommended interventions for the management of symptoms associated with amyotrophic lateral sclerosis (ALS). This study aimed to quantify the views of a range of healthcare professionals (HCPs) on the provision of these interventions in the United Kingdom. A total of 177 HCPs participated in an online survey. Significant differences were found between medical and allied HCPs' views on: whether HCPs adhere to policy and accept legal constraints when it comes to making gastrostomy available to people with ALS; the impressions that HCPs receive of the way patients and caregivers understand the effects of gastrostomy and NIV on symptoms and quality of life; and the challenges HCPs face when caring for patients who have refused gastrostomy. More widely available guidelines for the provision of gastrostomy and advice on the best way to impart information to patients and caregivers about gastrostomy and NIV appear to be needed. more...
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- 2013
12. Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial.
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Morrison KE, Dhariwal S, Hornabrook R, Savage L, Burn DJ, Khoo TK, Kelly J, Murphy CL, Al-Chalabi A, Dougherty A, Leigh PN, Wijesekera L, Thornhill M, Ellis CM, O'Hanlon K, Panicker J, Pate L, Ray P, Wyatt L, Young CA, Copeland L, Ealing J, Hamdalla H, Leroi I, Murphy C, O'Keeffe F, Oughton E, Partington L, Paterson P, Rog D, Sathish A, Sexton D, Smith J, Vanek H, Dodds S, Williams TL, Steen IN, Clarke J, Eziefula C, Howard R, Orrell R, Sidle K, Sylvester R, Barrett W, Merritt C, Talbot K, Turner MR, Whatley C, Williams C, Williams J, Cosby C, Hanemann CO, Iman I, Philips C, Timings L, Crawford SE, Hewamadduma C, Hibberd R, Hollinger H, McDermott C, Mils G, Rafiq M, Shaw PJ, Taylor A, Waines E, Walsh T, Addison-Jones R, Birt J, Hare M, and Majid T more...
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- Aged, Double-Blind Method, Female, Humans, Lithium Carbonate therapeutic use, Male, Middle Aged, Neuroprotective Agents therapeutic use, Survival Rate trends, Treatment Outcome, Amyotrophic Lateral Sclerosis drug therapy, Amyotrophic Lateral Sclerosis mortality
- Abstract
Background: Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival. We aimed to assess whether lithium improves survival in patients with ALS., Methods: The lithium carbonate in amyotrophic lateral sclerosis (LiCALS) trial is a randomised, double-blind, placebo-controlled trial of oral lithium taken daily for 18 months in patients with ALS. Patients aged at least 18 years who had ALS according to the revised El Escorial criteria, had disease duration between 6 and 36 months, and were taking riluzole were recruited from ten centres in the UK. Patients were randomly assigned (1:1) to receive either lithium or matched placebo tablets. Randomisation was via an online system done at the level of the individual by block randomisation with randomly varying block sizes, stratified by study centre and site of disease onset (limb or bulbar). All patients and assessing study personnel were masked to treatment assignment. The primary endpoint was the rate of survival at 18 months and was analysed by intention to treat. This study is registered with Eudract, number 2008-006891-31., Findings: Between May 26, 2009, and Nov 10, 2011, 243 patients were screened, 214 of whom were randomly assigned to receive lithium (107 patients) or placebo (107 patients). Two patients discontinued treatment and one died before the target therapeutic lithium concentration could be achieved. 63 (59%) of 107 patients in the placebo group and 54 (50%) of 107 patients in the lithium group were alive at 18 months. The survival functions did not differ significantly between groups (Mantel-Cox log-rank χ(2) on 1 df=1·64; p=0·20). After adjusting for study centre and site of onset using logistic regression, the relative odds of survival at 18 months (lithium vs placebo) was 0·71 (95% CI 0·40-1·24). 56 patients in the placebo group and 61 in the lithium group had at least one serious adverse event., Interpretation: We found no evidence of benefit of lithium on survival in patients with ALS, but nor were there safety concerns, which had been identified in previous studies with less conventional designs. This finding emphasises the importance of pursuing adequately powered trials with clear endpoints when testing new treatments., Funding: The Motor Neurone Disease Association of Great Britain and Northern Ireland., (Copyright © 2013 Elsevier Ltd. All rights reserved.) more...
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- 2013
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13. An MND/ALS phenotype associated with C9orf72 repeat expansion: abundant p62-positive, TDP-43-negative inclusions in cerebral cortex, hippocampus and cerebellum but without associated cognitive decline.
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Troakes C, Maekawa S, Wijesekera L, Rogelj B, Siklós L, Bell C, Smith B, Newhouse S, Vance C, Johnson L, Hortobágyi T, Shatunov A, Al-Chalabi A, Leigh N, Shaw CE, King A, and Al-Sarraj S
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- Age of Onset, Blotting, Western, Brain pathology, C9orf72 Protein, DNA genetics, Female, Fluorescent Antibody Technique, Humans, Immunohistochemistry, Male, Microscopy, Electron, Middle Aged, Spinal Cord pathology, Tissue Banks, Trinucleotide Repeat Expansion, Amyotrophic Lateral Sclerosis genetics, Amyotrophic Lateral Sclerosis psychology, Cerebellum pathology, Cerebral Cortex pathology, Cognition Disorders genetics, Cognition Disorders pathology, DNA-Binding Proteins genetics, Hippocampus pathology, Inclusion Bodies pathology, Motor Neuron Disease genetics, Motor Neuron Disease psychology, Proteins genetics, Proto-Oncogene Proteins c-myc genetics
- Abstract
The transactive response DNA binding protein (TDP-43) proteinopathies describe a clinico-pathological spectrum of multi-system neurodegeneration that spans motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) and frontotemporal lobar degeneration (FTLD). We have identified four male patients who presented with the clinical features of a pure MND/ALS phenotype (without dementia) but who had distinctive cortical and cerebellar pathology that was different from other TDP-43 proteinopathies. All patients initially presented with weakness of limbs and respiratory muscles and had a family history of MND/ALS. None had clinically identified cognitive decline or dementia during life and they died between 11 and 32 months after symptom onset. Neuropathological investigation revealed lower motor neuron involvement with TDP-43-positive inclusions typical of MND/ALS. In contrast, the cerebral pathology was atypical, with abundant star-shaped p62-immunoreactive neuronal cytoplasmic inclusions in the cerebral cortex, basal ganglia and hippocampus, while TDP-43-positive inclusions were sparse. This pattern was also seen in the cerebellum where p62-positive, TDP-43-negative inclusions were frequent in granular cells. Western blots of cortical lysates, in contrast to those of sporadic MND/ALS and FTLD-TDP, showed high p62 levels and low TDP-43 levels with no high molecular weight smearing. MND/ALS-associated SOD1, FUS and TARDBP gene mutations were excluded; however, further investigations revealed that all four of the cases did show a repeat expansion of C9orf72, the recently reported cause of chromosome 9-linked MND/ALS and FTLD. We conclude that these chromosome 9-linked MND/ALS cases represent a pathological sub-group with abundant p62 pathology in the cerebral cortex, hippocampus and cerebellum but with no significant associated cognitive decline., (© 2011 Japanese Society of Neuropathology.) more...
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- 2012
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14. The sex ratio in amyotrophic lateral sclerosis: A population based study.
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Manjaly ZR, Scott KM, Abhinav K, Wijesekera L, Ganesalingam J, Goldstein LH, Janssen A, Dougherty A, Willey E, Stanton BR, Turner MR, Ampong MA, Sakel M, Orrell RW, Howard R, Shaw CE, Leigh PN, and Al-Chalabi A more...
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- Adolescent, Adult, Aged, England epidemiology, Female, Humans, Male, Middle Aged, Risk Factors, Sex Factors, Young Adult, Amyotrophic Lateral Sclerosis epidemiology, Sex Ratio
- Abstract
Replicable risk factors for ALS include increasing age, family history and being male. The male: female ratio has been reported as being between 1 and 3. We tested the hypothesis that the sex ratio changes with age in a population register covering the south-east of England. The sex ratio before and after the age of 51 years was compared using a Z-test for proportions. Kendall's tau was used to assess the relationship between age group and sex ratio using incidence and prevalence data. Publicly available data from Italian and Irish population registers were compared with results. There was a significant difference in the proportion of females with ALS between those in the younger group (30.11%) and those in the older group (43.66%) (p = 0.013). The adjusted male: female ratio dropped from 2.5 in the younger group to 1.4 in the older group using prevalence data (Kendall's tau = -0.73, p = 0.039). Similar ratios were found in the Italian but not the Irish registry. We concluded that sex ratios in ALS may change with age. Over-representation of younger patients in clinic registers may explain the variation in sex ratios between studies. Menopause may also play a role. more...
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- 2010
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15. The association between ALS and population density: A population based study.
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Scott KM, Abhinav K, Wijesekera L, Ganesalingam J, Goldstein LH, Janssen A, Dougherty A, Willey E, Stanton BR, Turner MR, Ampong MA, Sakel M, Orrell R, Howard R, Shaw CE, Nigel Leigh P, and Al-Chalabi A more...
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- Amyotrophic Lateral Sclerosis etiology, England epidemiology, Female, Humans, London epidemiology, Male, Rural Population, Urban Population, Amyotrophic Lateral Sclerosis diagnosis, Amyotrophic Lateral Sclerosis epidemiology, Population Density, Registries
- Abstract
We aimed to assess whether rural residence is associated with amyotrophic lateral sclerosis in the south-east of England using a population based register. Previous studies in different populations have produced contradictory findings. Residence defined by London borough or non-metropolitan district at time of diagnosis was recorded for each incident case in the South-East England ALS Register between 1995 and 2005. Each of the 26 boroughs or districts of the catchment area of the register was classified according to population density. Age- and sex-adjusted incidence of ALS was calculated for each region and the relationship with population density tested by linear regression, thereby controlling for the underlying population structure. We found that population density in region of residence at diagnosis explained 25% of the variance in ALS rates (r = 0.5, p < 0.01). Thus, in this cohort in the south-east of England, people with ALS were more likely to be resident in areas of high population density at diagnosis. more...
- Published
- 2010
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16. Latent cluster analysis of ALS phenotypes identifies prognostically differing groups.
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Ganesalingam J, Stahl D, Wijesekera L, Galtrey C, Shaw CE, Leigh PN, and Al-Chalabi A
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- Adult, Age of Onset, Aged, Amyotrophic Lateral Sclerosis classification, Amyotrophic Lateral Sclerosis mortality, Cluster Analysis, Female, Humans, Male, Middle Aged, Phenotype, Prognosis, Regression Analysis, Survival Analysis, Amyotrophic Lateral Sclerosis diagnosis, Amyotrophic Lateral Sclerosis genetics, Motor Neurons metabolism
- Abstract
Background: Amyotrophic lateral sclerosis (ALS) is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes., Methods: Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method., Results: The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001). Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb) and time from symptom onset to diagnosis (p<0.00001)., Conclusion: The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research. more...
- Published
- 2009
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