RESUMO
PURPOSE: In preclinical studies, many stem cell/cellular interventions demonstrated robust regeneration and/or repair in case of SCI and were considered a promising therapeutic candidate. However, data from clinical studies are not robust. Despite lack of substantial evidence for the efficacy of these interventions in spinal cord injury (SCI), many clinics around the world offer them as "therapy." These "clinics" claim efficacy through patient testimonials and self-advertisement without any scientific evidence to validate their claims. Thus, SCS established a panel of experts to review published preclinical studies, clinical studies and current global guidelines/regulations on usage of cellular transplants and make recommendations for their clinical use. METHODS: The literature review and draft position statement was compiled and circulated among the panel and relevant suggestions incorporated to reach consensus. This was discussed and finalized in an open forum during the SCS Annual Meeting, ISSICON. RESULTS: Preclinical evidence suggests safety and clinical potency of cellular interventions after SCI. However, evidence from clinical studies consisted of mostly case reports or uncontrolled case series/studies. Data from animal studies cannot be generalized to human SCI with regard to toxicity prediction after auto/allograft transplantation. CONCLUSIONS: Currently, cellular/stem cell transplantation for human SCI is experimental and needs to be tested through a valid clinical trial program. It is not ethical to provide unproven transplantation as therapy with commercial implications. To stop the malpractice of marketing such "unproven therapies" to a vulnerable population, it is crucial that all countries unite to form common, well-defined regulations/legislation on their use in SCI. These slides can be retrieved from Electronic Supplementary Material.
Assuntos
Traumatismos da Medula Espinal/cirurgia , Transplante de Células-Tronco , Animais , Humanos , Guias de Prática Clínica como Assunto , Transplante de Células-Tronco/legislação & jurisprudência , Transplante de Células-Tronco/métodos , Transplante de Células-Tronco/normasRESUMO
BACKGROUND: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. METHODS AND FINDINGS: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population. CONCLUSIONS: The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions.
Assuntos
Transtornos do Neurodesenvolvimento/epidemiologia , Distribuição por Idade , Criança , Comportamento Infantil , Desenvolvimento Infantil , Pré-Escolar , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Índia/epidemiologia , Masculino , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/fisiopatologia , Transtornos do Neurodesenvolvimento/psicologia , Prevalência , Medição de Risco , Fatores de RiscoRESUMO
The Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka has a long tradition of excellence in education, teaching, research, and patient care. Its exceptional alumni, as well as current and past faculty members, have made considerable contributions to the development of neurological services throughout the world. The six decades of its existence have seen a momentous growth in clinical, investigative, and community Neurology. As a result of the immense scientific individual as well as collaborative contributions of the faculty members in various departments, the Institute has had the honour of attaining the status of an autonomous 'Institute of National Importance' under the Ministry of Health, Government of India, through a novel concept of collaboration and partnership of central and state governments. This article traces the dedicated pursuit of members of the Department of Neurology, NIMHANS, in managing neurologic diseases through compassionate patient-centred care, transformative research and education.
Assuntos
Doenças do Sistema Nervoso , Neurologia/história , Neurologia/métodos , Neurociências/história , Academias e Institutos , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Índia , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/história , Doenças do Sistema Nervoso/terapia , Neurociências/métodos , FotografaçãoRESUMO
While the past 2 decades have witnessed an increasing understanding of amyotrophic lateral sclerosis (ALS) arising from East Asia, particularly Japan, South Korea, Taiwan and China, knowledge of ALS throughout the whole of Asia remains limited. Asia represents >50% of the world population, making it host to the largest patient cohort of ALS. Furthermore, Asia represents a diverse population in terms of ethnic, social and cultural backgrounds. In this review, an overview is presented that covers what is currently known of ALS in Asia from basic epidemiology and genetic influences, through to disease characteristics including atypical phenotypes which manifest a predilection for Asians. With the recent establishment of the Pan-Asian Consortium for Treatment and Research in ALS to facilitate collaborations between clinicians and researchers across the region, it is anticipated that Asia and the Pacific will contribute to unravelling the uncertainties in ALS.
Assuntos
Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/epidemiologia , Doença dos Neurônios Motores/complicações , Doença dos Neurônios Motores/epidemiologia , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/mortalidade , Ásia/epidemiologia , Progressão da Doença , Humanos , Doença dos Neurônios Motores/genética , Doença dos Neurônios Motores/mortalidade , Fenótipo , SíndromeRESUMO
Growth and development of neuroepidemiology in India during the last four decades has been documented highlighting the historical milestones. The prevalence rates of the spectrum of neurological disorders from different regions of the country ranged from 967-4,070 with a mean of 2394 per 100,000 population, providing a rough estimate of over 30 million people with neurological disorders (excluding neuroinfections and traumatic injuries). Prevalence and incidence rates of common disorders including epilepsy, stroke, Parkinson's disease and tremors determined through population-based surveys show considerable variation across different regions of the country. The need for a standardized screening questionnaire, uniform methodology for case ascertainment and diagnosis is an essential requiste for generating robust national data on neurological disorders. Higher rates of prevalence of neurological disorders in rural areas, 6-8 million people with epilepsy and high case fatality rates of stroke (27-42%) call for urgent strategies to establish outreach neurology services to cater to remote and rural areas, develop National Epilepsy Control Program and establish stroke units at different levels of health care pyramid.
Assuntos
Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/epidemiologia , Epilepsia/epidemiologia , Humanos , Incidência , Índia/epidemiologia , Doença de Parkinson/epidemiologia , Prevalência , Acidente Vascular Cerebral/epidemiologia , Tremor/epidemiologiaRESUMO
Although the Madras motor neuron disease (MMND) was found three decades ago, its genetic basis has not been elucidated, so far. The symptom at onset was impaired hearing, upper limb weakness and atrophy. Since some clinical features of MMND overlap with mitochondrial disorders, we analyzed the complete mitochondrial genome of 45 MMND patients and found 396 variations, including 13 disease-associated, 2 mt-tRNA and 33 non-synonymous (16 MT-ND, 10 MT-CO, 3 MT-CYB and 4 MT-ATPase). A rare variant (m.8302A>G) in mt-tRNA(Leu) was found in three patients. We predict that these variation(s) may influence the disease pathogenesis along with some unknown factor(s).
Assuntos
DNA Mitocondrial/genética , Doença dos Neurônios Motores/genética , Adulto , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
Tuberculous meningitis (TBM) is a serious meningitic infection commonly found to occur in the developing countries endemic to tuberculosis. Based on the clinical features alone, the diagnosis of TBM can neither be made nor excluded with certainty. Unfortunately there is still no single diagnostic method that is both sufficiently rapid and sensitive. Most factors found to correlate with poor outcome can be directly traced to the stage of the disease at the time of diagnosis. The only way to reduce the mortality and morbidity is by early diagnosis and timely recognition of complications and institution of the appropriate treatment strategies.
Assuntos
Aracnoidite/diagnóstico , Quiasma Óptico/patologia , Tuberculose Meníngea/diagnóstico , Aracnoidite/terapia , Humanos , Prognóstico , Tuberculose Meníngea/terapiaRESUMO
Over-expression of efflux transporter P-glycoprotein (PgP) encoded by ABCB1 gene has been implicated in poor responsive epilepsy. Several genetic variants have been shown to influence the expression levels of P-glycoprotein. The aim of the present study was to investigate the role of ABCB1 polymorphisms: C1236T, G2677T/A and C3435T in determining drug response to first line antiepileptic drugs (AEDs) namely phenobarbitone, phenytoin, carbamazepine and valproate in North Indian cohort of epilepsy patients. DNA samples were obtained from 392 consecutive epilepsy patients, out of which 228 had completed follow-up evaluation at 12 months. After attaining steady state of the AEDs in the first two months of study, 133 patients showed complete freedom from seizures (no-seizure group) and 95 patients continued to have seizures (recurrent-seizures group) in the remaining period of study. Comparison of "no-seizure" and "recurrent-seizures" groups revealed no significant differences in allelic, genotypic and haplotypic frequencies for all the studied variants. In conclusion, our finding disproves a general association between ABCB1 polymorphisms and drug response in epilepsy patients.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adolescente , Adulto , Carbamazepina/uso terapêutico , Feminino , Genótipo , Humanos , Masculino , Farmacogenética , Fenobarbital/uso terapêutico , Fenitoína/uso terapêutico , Ácido Valproico/uso terapêutico , Adulto JovemAssuntos
Braço/fisiopatologia , Doença dos Neurônios Motores/classificação , Doença dos Neurônios Motores/diagnóstico , Músculo Esquelético/fisiopatologia , Atrofia Muscular/classificação , Atrofia Muscular/diagnóstico , Adulto , Fatores Etários , Idade de Início , Braço/inervação , Diagnóstico Diferencial , Progressão da Doença , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/fisiopatologia , Músculo Esquelético/inervação , Atrofia Muscular/fisiopatologia , Fenótipo , Fatores de Tempo , Adulto JovemRESUMO
Amyotrophic Lateral Sclerosis is a progressive disease causing degeneration of upper and lower motor neurons with an average survival of 2 to 3 years. We retrospectively analyzed 1,153 patients of classical sporadic ALS seen over 30 years for the clinical manifestations and survival pattern. There were 855 (74.2%) men and 298 (25.8%) women with a M:F ratio of 3:1. The mean age of onset was 46.2+/-14.1 years (18-85) and the mean duration of illness at evaluation was 17.7+/-20.7 months (0.5-180). Mean age of onset for bulbar onset group was 52.8+/-11.6 and for limb onset was 43.7+/-14.1 (p<0.0001). One third of patients had onset before 40 years of age. The overall median survival duration (MSD) was 114.8+/-25.9(SE) months (3.3-194.4). Survival did not differ between the men [101.7+/-27.4(SE)] and women [118.9+/-6.3(SE)]. Information on death was available in 124 patients. The mean age at death was 52.95 years (25.7-82.6). The MSD for bulbar onset group was 55.9+/-2.9(SE) months and for limb onset group 177.9+/-3.2(SE) (p<0.0001). Gender did not have an effect on the survival period. The clinical manifestations are similar to findings from other developing countries with regards to age of onset, sex ratio and survival. When compared to studies among Caucasians the age of onset was one to two decades earlier and the male preponderance was more. The survival pattern is close to those reported from developing countries particularly from Africa and among Asian immigrants to the West, while it is significantly longer compared to Caucasians who generally have a dismal prognosis. Thus, Indians appear to have a relatively younger age of onset and prolonged survival suggesting the relatively slow course of ALS among Indian patients.
Assuntos
Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/mortalidade , Adolescente , Adulto , Fatores Etários , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/fisiopatologia , Esclerose Lateral Amiotrófica/terapia , Estudos Transversais , Feminino , Seguimentos , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Análise de SobrevidaRESUMO
We have previously shown in our laboratory that cerebrospinal fluid from ALS patients (ALS-CSF) contains putative toxic factor(s). In the present study we determined the effect of ALS-CSF on the integrity of the Golgi apparatus of spinal motor neurons in the neonatal rats. CSF was injected intrathecally into three-day-old rat pups and subsequently the ultrastructural changes in the motor neurons were studied after 48 h, 1, 2 and 3 weeks. We observed that ALS-CSF causes fragmentation of the Golgi apparatus in a considerable number of motor neurons in the spinal cord. This was further confirmed when motor neurons were stained with an antibody against a medial Golgi protein (MG160). Thus, we suggest that the putative toxin(s) present in ALS-CSF may cause impairment in the protein processing leading to motor neuron death.