RESUMEN
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.
Asunto(s)
Traumatismos de la Médula Espinal/cirugía , Trasplante de Células Madre , Animales , Humanos , Guías de Práctica Clínica como Asunto , Trasplante de Células Madre/legislación & jurisprudencia , Trasplante de Células Madre/métodos , Trasplante de Células Madre/normasRESUMEN
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.
Asunto(s)
Trastornos del Neurodesarrollo/epidemiología , Distribución por Edad , Niño , Conducta Infantil , Desarrollo Infantil , Preescolar , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , India/epidemiología , Masculino , Trastornos del Neurodesarrollo/diagnóstico , Trastornos del Neurodesarrollo/fisiopatología , Trastornos del Neurodesarrollo/psicología , Prevalencia , Medición de Riesgo , Factores de RiesgoRESUMEN
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.
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Enfermedades del Sistema Nervioso , Neurología/historia , Neurología/métodos , Neurociencias/historia , Academias e Institutos , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Humanos , India , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/historia , Enfermedades del Sistema Nervioso/terapia , Neurociencias/métodos , FotograbarRESUMEN
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.
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Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/epidemiología , Enfermedad de la Neurona Motora/complicaciones , Enfermedad de la Neurona Motora/epidemiología , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/mortalidad , Asia/epidemiología , Progresión de la Enfermedad , Humanos , Enfermedad de la Neurona Motora/genética , Enfermedad de la Neurona Motora/mortalidad , Fenotipo , SíndromeRESUMEN
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.
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Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/epidemiología , Epilepsia/epidemiología , Humanos , Incidencia , India/epidemiología , Enfermedad de Parkinson/epidemiología , Prevalencia , Accidente Cerebrovascular/epidemiología , Temblor/epidemiologíaRESUMEN
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.
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Aracnoiditis/diagnóstico , Quiasma Óptico/patología , Tuberculosis Meníngea/diagnóstico , Aracnoiditis/terapia , Humanos , Pronóstico , Tuberculosis Meníngea/terapiaRESUMEN
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.
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Esclerosis Amiotrófica Lateral/epidemiología , Esclerosis Amiotrófica Lateral/mortalidad , Adolescente , Adulto , Factores de Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/terapia , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , Análisis de SupervivenciaRESUMEN
From 1977 through 1981, we examined 23 patients with single-limb atrophy. Thirteen had upper-limb and ten had lower-limb involvement. The characteristic clinical features were insidious onset in the second and third decades, male preponderance, sporadic occurrence, wasting and weakness confined to one limb, and absence of involvement of the cranial nerves, cerebrum, brain stem, and sensory system. The electromyographic features, along with histologic features of neurogenic atrophy, were suggestive of an anterior horn cell lesion. The slow progression of illness for two to four years followed by a stationary phase was observed. There was no clinical evidence of involvement of the other three limbs even in patients with long-standing illness of ten to 15 years' duration.
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Atrofia Muscular/fisiopatología , Adolescente , Adulto , Brazo , Femenino , Humanos , Pierna , Masculino , Neuronas Motoras , Atrofia Muscular/diagnóstico , Atrofia Muscular/patología , Conducción Nerviosa , Enfermedades Neuromusculares/fisiopatologíaRESUMEN
Madras motor neuron disease (MMND) has the characteristic features of onset in the young, atrophy and weakness of the limbs, multiple cranial nerve palsies particularly the seventh, ninth to twelfth and sensorineural hearing loss with unique geographic distribution to southern part of India. During a period of 28 years (1974-2001), 7 (13%) among 54 patients of MMND seen at a tertiary referral center at Bangalore, India, had the additional features of optic atrophy in all and cerebellar involvement in three of them. There were three males and four females, the mean age at onset was 11.7 years, with a mean duration of illness of 6.4 years. All except one patient were ambulant and independent in the activities of daily living. Family history of MMND was present in more than a quarter (28.6%) of patients. Compared to MMND, these patients had onset of illness at a younger age and family history was more frequently observed, however, these differences were not statistically significant. Bulbar palsy was an invariable feature, being present in all patients compared to 38.3% of MMND and the difference was statistically significant (p=0.003). This clinical profile may be considered to be a variant of Madras motor neuron disease (MMNDV).
Asunto(s)
Enfermedad de la Neurona Motora/diagnóstico , Adolescente , Adulto , Edad de Inicio , Parálisis Bulbar Progresiva/etiología , Enfermedades Cerebelosas/etiología , Niño , Preescolar , Consanguinidad , Progresión de la Enfermedad , Resultado Fatal , Femenino , Pérdida Auditiva Sensorineural/etiología , Humanos , India , Masculino , Enfermedad de la Neurona Motora/complicaciones , Debilidad Muscular/etiología , Atrofia Óptica/etiología , LinajeRESUMEN
Spinal arachnoiditis, a complication of tuberculous meningitis, is not uncommon; it may develop despite specific chemotherapy and steroids, and existing avenues of treatment for it are unsatisfactory. The enzyme hyaluronidase, by virtue of its action of hydrolysing the glucosaminidic bonds of hyaluronic acid and other mucopolysaccharides of the ground substance, offers a promising mode of treatment. Sixty-six patients with spinal arachnoiditis secondary to tuberculous meningitis were seen over an 8-year period. All these patients received antituberculous drugs and steroids; 39 of them (group A), who, in addition, were given intrathecal hyaluronidase, fared better than the remaining 27 (group B), who did not receive this enzyme. This study was non-randomised. The disability and functional deficit score showed a significant decrease from 7.6 to 3.7 in the enzyme-treated group in contrast to a mild change from 8.1 to 6.9 in the untreated group. Further, in group A the mortality was 5.2% whereas in group B it was 25.9%. There was a marked 5-fold decrease in mean CSF protein in group A while in group B there was no significant change. There were no serious side effects due to repeated administration of intrathecal hyaluronidase. Thus this study provides convincing evidence of the therapeutic role of hyaluronidase in the management of tuberculous spinal arachnoiditis and replicates our earlier observation of the safety of hyaluronidase given intrathecally.
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Aracnoiditis/tratamiento farmacológico , Hialuronoglucosaminidasa/uso terapéutico , Tuberculosis Meníngea/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antituberculosos/uso terapéutico , Aracnoiditis/líquido cefalorraquídeo , Aracnoiditis/mortalidad , Niño , Evaluación de Medicamentos , Proteínas de la Matriz Extracelular/efectos de los fármacos , Femenino , Humanos , Hialuronoglucosaminidasa/farmacología , India/epidemiología , Inyecciones Espinales , Masculino , Persona de Mediana Edad , Prednisolona/uso terapéutico , Índice de Severidad de la Enfermedad , Tuberculosis Meníngea/líquido cefalorraquídeo , Tuberculosis Meníngea/mortalidadRESUMEN
Based on the evidence that autoimmunity may play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS), a variety of immunomodulating agents have been used in the treatment. In an uncontrolled trial we treated 44 patients of ALS with intravenous cyclophosphamide (IVCP) at a total dose of 1.5 g/m2 given over a period of 8 to 10 days. The patients were evaluated using neurological score which included bulbar, motor and daily activity scores before and following treatment. Twenty three patients showed a significant improvement (P=<0.001) in the composite and the individual scores. The improvement persisted only for 2 to 3 months. Amongst them the severely (7) and moderately (16) affected (score less than or more than 150) showed almost a similar response to treatment. A comparison of the improved group of 23 patients with the unimproved group of 21 patients did not reveal any significant factors which influenced the response to IVCP. However, there was a suggestion that patients below the age of 60 years and a duration of illness less than 12 months may respond to the drug. In conclusion, treatment with intravenous cyclophosphamide resulted in mild and temporary improvement in clinical status of the patients with amyotrophic lateral sclerosis. This may be considered as an alternative method of treatment in developing countries where newer drugs are not available and affordable.
Asunto(s)
Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Inmunosupresores/uso terapéutico , Adulto , Anciano , Esclerosis Amiotrófica Lateral/fisiopatología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Sistema Nervioso/efectos de los fármacos , Sistema Nervioso/fisiopatología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Our earlier studies have shown that cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS), when intrathecally injected into the neonatal rats, produces an aberrant phosphorylation of neurofilaments (NF) in the ventral horn neurons and reactive astrogliosis in the spinal cord. We wanted to investigate the effect of cyclophosphamide in the spinal cords of neonatal rats exposed to ALS-CSF. A single dose (5 microg in 5 microl saline) of cyclophosphamide was injected, 24 h after the administration of CSF samples from ALS and non-ALS neurological patients into the spinal subarachnoid space of 3-day-old rat pups. Rats were sacrificed after a period of 24 h, and stained with antibodies against the phosphorylated NF (SMI-31 antibody) and glial fibrillary acidic protein (GFAP). Cyclophosphamide treatment resulted in a 50% decrease in the number of SMI-31 stained neuronal soma in ventral horns of spinal cords of ALS-CSF exposed rats. This was accompanied by a decrease in the number of GFAP immunoreactive astrocytes. Furthermore, lactate dehydrogenase (LDH) activity was also decreased significantly, following cyclophosphamide treatment. These results suggest that cyclophosphamide could exert a neuroprotective effect against the neurotoxic action of factor(s) present in the ALS-CSF.
Asunto(s)
Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Células del Asta Anterior/efectos de los fármacos , Proteínas del Líquido Cefalorraquídeo/farmacología , Ciclofosfamida/farmacología , Inmunosupresores/farmacología , Degeneración Nerviosa/prevención & control , Fármacos Neuroprotectores/farmacología , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/fisiopatología , Animales , Animales Recién Nacidos/metabolismo , Células del Asta Anterior/patología , Astrocitos/efectos de los fármacos , Astrocitos/patología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Proteína Ácida Fibrilar de la Glía/efectos de los fármacos , Proteína Ácida Fibrilar de la Glía/metabolismo , Gliosis/inducido químicamente , Gliosis/fisiopatología , Gliosis/prevención & control , Inmunohistoquímica , L-Lactato Deshidrogenasa/efectos de los fármacos , L-Lactato Deshidrogenasa/metabolismo , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/fisiopatología , Proteínas de Neurofilamentos/efectos de los fármacos , Proteínas de Neurofilamentos/metabolismo , Fosforilación/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Congenital muscular dystrophy (CMD) is a relatively uncommon disease with a controversial nosological status. That collagen synthesis could be the primary abnormality has been suggested earlier (Fidzianska et al., 1982). Amongst eighteen cases of CMD diagnosed during the past twelve years, muscle biopsy in three cases revealed prominence of myofibre necrosis and phagocytosis, and serum CPK was markedly elevated suggesting a rapidly progressive form. In twelve cases, marked increase in endomysial collagen, pronounced fallout of myofibres and significant fibre diameter variation was seen. This was associated with myonecrosis and regenerative activity of mild degree resembling the classical form of CMD. In the remaining three cases, polyfocal, polyphasic necrosis was noticed. Fibre splitting was more frequently observed, better delineated in the enzyme histochemical preparations, affecting both fibre types, while endomysial fibrofatty tissue was only moderately increased. The histomorphology in the latter group resembled that of limb girdle dystrophy. Ultrastructural findings in all the eighteen cases correlated well with light microscopic observations. lmmunohistochemical studies done on three of the eighteen cases showed normal localization of dystrophin protein. Such variable histomorphology, revealing a spectrum of myopathic features, suggests that the primary change in CMD is likely to be in the myofibre rather than in collagen synthesis.
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Músculo Esquelético/patología , Distrofias Musculares/patología , Biopsia , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Microscopía Electrónica , Fibras Musculares Esqueléticas/patología , Fibras Musculares Esqueléticas/ultraestructura , Músculo Esquelético/ultraestructura , Distrofias Musculares/congénitoRESUMEN
This study reports the detection of autoantibodies to myelin basic protein (MBP) and neurofilament proteins (NFP) in serum and cerebrospinal fluid (CSF) of Japanese encephalitis patients. The diagnosis of Japanese encephalitis was confirmed in 72 patients by the presence of virus specific antibodies to JEV in the CSF (28/72), viral antigen in the CSF (19/72) and simultaneous presence of both antigen and JEV antibodies in the CSF in 25/72 patients. Autoantibodies to either purified NFP (10) or MBP (8) or both (17) were detected in the CSF of 35 patients by ELISA in contrast with the control CSF samples. Amongst them 20 had similar antibodies in the serum as well. Correlation of immunological findings with the clinical outcome revealed that the presence of autoantibodies in the CSF especially to NFP was associated with a fatal outcome (P < 0.05).
Asunto(s)
Autoanticuerpos/líquido cefalorraquídeo , Encefalitis Japonesa/líquido cefalorraquídeo , Neuronas/inmunología , Adolescente , Adulto , Antígenos Virales/análisis , Western Blotting , Niño , Preescolar , Virus de la Encefalitis Japonesa (Especie)/inmunología , Encefalitis Japonesa/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Lactante , Masculino , Proteína Básica de Mielina/inmunología , Proteínas de Neurofilamentos/inmunología , Pruebas de Neutralización , Resultado del TratamientoRESUMEN
A patient with a rare case of Klippel-Trenaunay-Weber syndrome presented with paraplegia due to compression by a vertebral and epidural cavernous hemangioma. The metameric distribution of the large cutaneous vascular nevus provided the clinical clue to the nature of the spinal lesion. The association of the two lesions is explained in the basis of developmental anomaly.