RESUMO
Mutations in the SPG7 gene were initially reported in patients with autosomal recessive hereditary spastic paraplegia (HSP). Recent works suggested a dominant effect for some SPG7 mutations. To characterize the SPG7 mutational spectrum in a large cohort of Spanish HSP patients, we sequenced the whole SPG7 gene in a total of 285 Spastic Paraplegia patients. Large gene rearrangements were also ascertained in some patients. We found a total of 14 SPG7 mutations (12 new) in 14 patients; 2 were large deletions. All the mutation carriers had an adult onset age but only five (35%) had a complicated phenotype. We identified a single mutation in 13 patients. Familial analysis suggested a dominant inheritance for one (p.Leu78*) of these mutations. Carriers of the rare p.A510V variant were significantly more frequent in patients vs healthy controls (3% vs 1%), suggesting a pathogenic role for this SPG7 variant. We reported a high frequency of patients with only one SPG7 mutation, and a putative pathogenic role for the p.A510V variant.
Assuntos
Substituição de Aminoácidos , Metaloendopeptidases/genética , Mutação , Paraplegia Espástica Hereditária/genética , ATPases Associadas a Diversas Atividades Celulares , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Análise Mutacional de DNA , Frequência do Gene , Genes Dominantes , Predisposição Genética para Doença , Testes Genéticos , Genótipo , Humanos , Lactente , Pessoa de Meia-Idade , Fenótipo , Espanha , Paraplegia Espástica Hereditária/diagnóstico , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: the study is aimed to report neurologic manifestations in a population of patients with inflammatory bowel disease in order to address its clinical characteristics. METHODS: we conducted a retrospective study based on a computer-guided search, of patients with Crohn's disease or ulcerative colitis diagnosed at three hospitals in Spain spanning from 2000 through 2008. Patients were classified into different clinical groups based on the type of neurologic involvement. Only patients without iatrogenic complications, vitamin deficiencies, or known cerebrovascular risk factors were included. RESULTS: we identified and reviewed the records of eighty-four inflammatory bowel disease patients with neurologic symptoms: thirteen patients with ulcerative colitis and twelve patients with Crohn's disease associated with neurologic complications were identified. Their ages ranged from 17 to 74 years. There was a slight predominance of women. Only four of them have another extra-intestinal manifestation. Most of the patients developed neurologic manifestations coincidental or after digestive symptoms appeared. Demyelinating disease was the most frequent manifestation observed (8 patients). Cerebrovascular, peripheral nerve, and epilepsy disorders were diagnosed in 6, 5, and 3 patients, respectively. One patient with myoclonus, one with amyotrophic lateral sclerosis, and one with sensorineural hearing loss were found. CONCLUSIONS: although an incidence could not be obtained, this population of patients with inflammatory bowel disease have a low frequency of severe neurologic disorders. Neurologic diseases, such as cerebrovascular disease, demyelinating disease, and peripheral neuropathy, could be associated with Crohn's disease and ulcerative colitis.
Assuntos
Colite Ulcerativa/complicações , Doença de Crohn/complicações , Doenças do Sistema Nervoso/complicações , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , EspanhaRESUMO
A monophasic Salmonella enterica serovar 4,[5],12:i:- phage type DT193 emerged as the dominant serovar in Luxembourg in 2006, when it caused two major outbreaks involving 133 laboratory-confirmed human cases, 24 hospitalisations, and one death. The outbreak strain had an uncommon pulsed-field gel electrophoresis pattern STYMXB.0031 and antibiotic resistance profile ASSuT. A high proportion of cases were clustered in institutions for the elderly and in day-care centers. Strains identical to the outbreak strain were recovered from two control meals, a nappy changing table, retail sausages and caecal porcine samples at an abattoir. Locally produced pork meat is strongly suspected to have been the vehicle for the outbreaks, although the precise mechanisms remain unclear.
Assuntos
Surtos de Doenças/estatística & dados numéricos , Contaminação de Alimentos/estatística & dados numéricos , Gastroenterite/epidemiologia , Vigilância da População , Intoxicação Alimentar por Salmonella/epidemiologia , Salmonella enterica/isolamento & purificação , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Gastroenterite/microbiologia , Humanos , Incidência , Luxemburgo/epidemiologia , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Fatores de Risco , Intoxicação Alimentar por Salmonella/microbiologiaRESUMO
INTRODUCTION: Although spinal fistulas account for 70% of all spinal arteriovenous malformations, they are an underdiagnosed condition. The arteriovenous shunt produces vascular congestion that gives rise to a progressive myelopathy, sometimes irreversible if it is not treated in the early stages. AIM: To describe the clinicoradiological characteristics of a series of patients with spinal fistulas. PATIENTS AND METHODS: A retrospective search was conducted for patients diagnosed with a spinal fistula who were hospitalised in the neuroscience area of a tertiary care hospital. RESULTS: A total of 19 patients (7 females and 12 males) were identified, with a mean age of 56 years. The spinal fistula was type I in 79% of patients, and a dorsal location was the most frequent. Most of the cases (90%) presented a progressive course. Magnetic resonance imaging was used in the diagnosis in 74% of the patients. In four cases angiography was required to reach a diagnosis, and in one of them it was necessary to perform an intraoperative biopsy. Three lumbar punctures were performed, two of which revealed lymphocytic pleocytosis and high protein levels in cerebrospinal fluid. The average diagnostic delay was nine months. Seventy-nine per cent of the patients were treated and only 10% of them improved. CONCLUSIONS: When faced with a clinical picture suggestive of a spinal fistula, a diagnostic spinal angiography must be carried out, although the patient under study may present atypical cerebrospinal fluid characteristics and normal results in magnetic resonance imaging of the spinal cord.
TITLE: Descripcion de una serie hospitalaria de pacientes con fistula espinal.Introduccion. Aunque las fistulas espinales suponen el 70% de las malformaciones arteriovenosas espinales, son una entidad infradiagnosticada. El shunt arteriovenoso produce una congestion vascular que da lugar a una mielopatia progresiva, en ocasiones irreversible si no se trata de forma precoz. Objetivo. Describir las caracteristicas clinicorradiologicas de una serie de pacientes con fistula espinal. Pacientes y metodos. Se realizo una busqueda retrospectiva de pacientes con diagnostico de fistula espinal ingresados en el area de neurociencias de un hospital de tercer nivel asistencial. Resultados. Se identificaron 19 pacientes (7 mujeres y 12 varones) con una edad media de 56 años. La fistula espinal fue de tipo I en un 79% de los pacientes y la localizacion dorsal fue la mas frecuente. La mayoria de los casos presento un curso progresivo (90%). Un 74% de los pacientes se diagnostico mediante resonancia magnetica. En cuatro casos fue necesaria la realizacion de una angiografia para llegar al diagnostico, y en uno de ellos se preciso una biopsia intraoperatoria. Se realizaron tres punciones lumbares, en dos de las cuales se objetivo pleocitosis linfocitaria e hiperproteinorraquia. El retraso diagnostico medio fue de nueve meses. Se trato a un 79% de los pacientes, y de ellos solo mejoro el 10%. Conclusiones. Ante una clinica sugestiva de fistula espinal, debe realizarse una angiografia espinal diagnostica aunque el paciente estudiado pueda presentar caracteristicas licuorales atipicas y normalidad en la resonancia magnetica medular.
Assuntos
Fístula Arteriovenosa/patologia , Malformações Vasculares do Sistema Nervoso Central/patologia , Medula Espinal/patologia , Diagnóstico Tardio , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Several drugs can induce the development of aseptic meningitis. Drug-induced aseptic meningitis (DIAM) can mimic an infectious process as well as meningitides that are secondary to systemic disorders for which these drugs are used. Thus, DIAM constitutes a diagnostic and patient management challenge. Cases of DIAM were reviewed through a MEDLINE literature search (up to June 1998) to identify possible clinical and laboratory characteristics that would be helpful in distinguishing DIAM from other forms of meningitis or in identifying a specific drug as the culprit of DIAM. Our review showed that nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, intravenous immunoglobulins, and OKT3 antibodies (monoclonal antibodies against the T3 receptor) are the most frequent cause of DIAM. Resolution occurs several days after drug discontinuation and the clinical and cerebrospinal fluid profile (neutrophilic pleocytosis) do not allow DIAM to be distinguished from infectious meningitis. Nor are there any specific characteristics associated with a specific drug. Systemic lupus erythematosus seems to predispose to NSAID-related meningitis. We conclude that a thorough history on prior drug intake must be conducted in every case of meningitis, with special focus on those aforementioned drugs. If there is a suspicion of DIAM, a third-generation cephalosporin seems a reasonable treatment option until cerebrospinal fluid cultures are available.
Assuntos
Meningite Asséptica/induzido quimicamente , Antibacterianos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Diagnóstico Diferencial , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Imunossupressores/efeitos adversos , Meningite Asséptica/líquido cefalorraquidiano , Meningite Asséptica/diagnóstico , Muromonab-CD3/efeitos adversos , Fatores de RiscoRESUMO
The use of 30 to 50% ethanol solutions to extract the nucleotides from HTC and A-459 cells results in dinucleoside tetraphosphate (Ap4X) levels 3-30-fold as high as those obtained by 5% classical trichloracetic acid extraction, while ATP levels are identical in both cases. The amplification factor varies with the percentage of ethanol and duration of contact between the cells and the extraction mixture. It remains constant for the HTC cells during cell growth, but exhibits a maximum for the A-459 cells towards the end of the exponential growth period. The incorporation of radioactivity in Ap4X when [alpha-32P]ATP is added to the extraction mixture suggests an Ap4X neosynthesis in the presence of ethanol. The results carried out in the presence of pyrophosphate, EDTA and zinc acetate strongly suggest that aminoacyl-tRNA synthetases could be responsible for the increase in Ap4A content with ethanol treatment. Nevertheless, the effect of ethanol is probably not the result of an activation of these enzymes, but rather, as already suggested by earlier results in our laboratory, the result of a fast inactivation of the degradation enzymes.
Assuntos
Fosfatos de Dinucleosídeos/metabolismo , Etanol/farmacologia , Trifosfato de Adenosina/metabolismo , Difosfatos/metabolismo , Humanos , Técnicas In Vitro , Fenilalanina-tRNA Ligase/metabolismo , Células Tumorais Cultivadas , Zinco/farmacologiaRESUMO
Asynchronous and synchronized cultures of A549 and HTC cells were used to detect possible, cell cycle or cell density specific variations in the intracellular pools of dinucleoside tetraphosphates (Ap4X). No important variations of the nucleotide pools were observed during cell growth. When HTC cells were released from mitotic arrest, a decrease by a factor of N3 Ap4X and ATP levels was observed when the cells entered the G1 phase. This decrease is essentially due to cell doubling. When A549 cells were released from an arrest at the G1/S boundary, the nucleotide pool size increased slightly during the G2 phase just before mitosis. This result is in agreement with both earlier data from our laboratory and the observed decrease in Ap4X pool after release from mitotic-arrested HTC cells. These results suggest that the Ap4X and ATP pools are only subjected to very small variations during the cell cycle, essentially in the G2 phase and after mitosis.
Assuntos
Ciclo Celular , Divisão Celular , Oligonucleotídeos/metabolismo , Trifosfato de Adenosina/metabolismo , Benzimidazóis/farmacologia , Carcinoma Hepatocelular , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Fosfatos de Dinucleosídeos , Humanos , Neoplasias Hepáticas , Neoplasias Pulmonares , Mitose , NocodazolRESUMO
BACKGROUND: Patients with late-onset Alzheimer's disease show a higher frequency of the APOE-4 than controls. The usefulness of the APOE genotyping in the diagnosis of the disease is controversial. Recently, an age dependent prevalence of APOE-4 in Alzheimer's disease has been described, with a maximum frequency for patients with an age at onset between 65 and 80 years. Additionally, the APOE-4 frequency in healthy controls is similar among the different age-groups, including healthy octogenarians. These data suggest that APOE-4 determines when and not who will develop the disease. PATIENTS AND METHODS: The APOE genotype was defined following a previously described PCR-protocol. We analysed 120 patients with clinically defined probable Alzheimer's disease and 250 controls from the same Caucasian population (Austrias, Northern Spain). RESULTS: We found a significantly higher frequency of the APOE-4 in patients, compared to controls (p = 0.00001). The prevalence of this allele was 65% among patients with an age at onset 66-70, falling to 36% and 18% in patients younger than 65 and older than 80 years, respectively. The average age (SD) at onset did not differ between the E-44 (69 years), E-34 (73 years) and E-33 (73 years). APOE-4 frequency was similar between the different age-groups of controls, including healthy octogenarians. CONCLUSIONS: In Asturias, APOE genotyping can not be used for the presimptomatic diagnosis of Alzheimer's disease. However, individuals carrying this allele would have a higher probability of developing the disease at an age between 65 and 80 years if they are predisposed (genetically and/or environmentally) to the disease.
Assuntos
Alelos , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Apolipoproteínas E/genética , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Área Programática de Saúde , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Espanha/epidemiologiaRESUMO
Pathogenic mutations in the leucine-rich repeat kinase 2 gene (LRRK2; PARK8) have been implicated in autosomal dominant, late-onset parkinsonism. The LRRK2 6055G > A (G2019S) mutation is the most common reported to date, and has been observed in a number of different European populations. So far, only the LRRK2 4321C > G (R1441G) mutation has been identified in the Spanish population. Herein we have assessed the frequency of G2019S in a referral-based series of 225 patients with Parkinson's disease (PD) from the region of Asturias, Northern Spain. The mutant allele was identified in five (2.7%) of the sporadic late-onset patients and was not present in control subjects. All carriers displayed genetic profiles consistent with the same haplotype, as previously reported for Lrrk2 G2019S-positive subjects. None of these patients presented with a family history of parkinsonism at the time of diagnosis. Thus, approximately 5% of sporadic patients with PD from the North of Spain have either Lrrk2 G2019S or R1441G substitutions.
Assuntos
Predisposição Genética para Doença , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Idoso , Análise Mutacional de DNA , Feminino , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Mutação , Polimorfismo de Nucleotídeo Único , EspanhaRESUMO
INTRODUCTION: There are many studies that analyze the clinical course of multiple sclerosis (MS), but only a few of them observed patients from their first episode. We report a MS series of patients longitudinally evaluated from the onset of the disease and compare outcome between immunosuppressive treatment and non-treatment groups. PATIENTS AND METHODS: Patients were included when their follow-up was at least three years and serial examination was available. Poser's criteria were used for diagnosis. We measured neurological impairment according to Kurtzke's expanded disability status scale (EDSS). RESULTS: Fifty-five MS patients were followed-up. Forty-six had clinically defined and nine clinically probable MS. Thirty-three patients had relapsing-remitting, 11 had secondary-progressive and 11 had primary-progressive MS. Mean age of onset of the disease was 31.1 years and mean duration of follow-up was seven years. Pyramidal weakness and sensory symptoms were the most common initial manifestations. Median time to reach EDSS-3 and EDSS-6 from onset was 4.5 and 7.5 years, respectively. From a total of 23 patients with follow-up of 10 or more years, 11 (48 %) had benign MS. The average time from onset of MS to secondary-progressive was 6.1 years. There were no significant differences between treatment and non-treatment patients. CONCLUSION: Longitudinal studies starting from early clinical course of MS are most useful in determining its semeiology, clinical pattern and outcome. Our results call for caution in initiating early immunosuppressive or immunomodulatory therapy.
Assuntos
Esclerose Múltipla/fisiopatologia , Adulto , Área Programática de Saúde , Avaliação da Deficiência , Humanos , Estudos Longitudinais , Esclerose Múltipla/epidemiologia , Espanha/epidemiologiaRESUMO
Neurotrophic factors are molecules that regulate neuronal survival, nervous system plasticity and many other physiological functions of neuronal and glial cells, as well as some non-neuronal tissues. They have been involved in the etiopathogenesis of some neurodegenerative disorders, and some of them have been proposed as potential treatments for these diseases on the basis of in vitro experiments and animal models. The main neurotrophic factor families with potential therapeutic applications include the family of neurotrophins (NGF, BDNF or NT-3), GDNF and related neurotrophic factor, CNTF and the members of the IGF family. Some of these molecules have already been tested in clinical trials with contradictory results. One of the major challenges to their clinical use is the difficulty to deliver them into the central nervous system. Nevertheless, solid rational exists for the possible use of neurotrophic factors in the treatment of Alzheimer's and Parkinson's diseases, peripheral neuropathies or amyotrophic lateral sclerosis. This review compiles the essential aspects of neurotrophic factors and the current studies of their clinical relevance and therapeutic potentialities. Future directions for further research are also discussed.
Assuntos
Fatores de Crescimento Neural/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Animais , Lesões Encefálicas/tratamento farmacológico , Ensaios Clínicos como Assunto , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Humanos , Fatores de Crescimento Neural/metabolismo , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Somatomedinas/metabolismoRESUMO
Mirror writing is inverse writing that can only be read with the help of a mirror. It is generally associated with dominant hemisphere lesions and affects only one hand. We describe the case of a patient who, after cranial injury, developed bimanual mirror writing for letters but no other focal neurological symptom. The only abnormal complementary finding was a zone of left parieto-occipital hypoperfusion visibly by SPECT. No signs of psychological disorder were present to which the dysgraphia could be attributed. Symptoms disappeared after three months. We conclude that isolated bimanual mirror letter writing may be an expression of reversible parieto-occipital dysfunction of the dominant hemisphere.
Assuntos
Lesões Encefálicas/complicações , Dominância Cerebral , Redação , Adolescente , Feminino , Humanos , Lobo Occipital/irrigação sanguínea , Lobo Parietal/irrigação sanguínea , Fluxo Sanguíneo RegionalRESUMO
Four examples of occipital condyle syndrome, that is, unilateral occipital pain and ipsilateral tongue paralysis due to selective erosion of the occipital condyle, are reported. The four patients complained of a continuous, severe, unilateral, occipital pain which kept them with the head rotated to the side of the pain and held with their hands. The pain became unbearable with head rotation to the nonpainful side and with unilateral suboccipital palpation. The onset of this very characteristic unilateral headache antedated by as long as 2 1/2 months the ipsilateral hypoglossal paralysis. The occipital condyle syndrome may be the first manifestation of cancer or of chronic inflammatory lesions; recognition of this distinctive headache enables the clinical diagnosis to be made.
Assuntos
Cefaleia/etiologia , Nervo Hipoglosso , Paralisia/etiologia , Neoplasias Cranianas/complicações , Crânio , Língua , Idoso , Doenças dos Nervos Cranianos , Feminino , Cefaleia/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Cranianas/diagnóstico , Neoplasias Cranianas/secundário , SíndromeRESUMO
An association between a five-base-pair deletion/insertion DNA polymorphism at the alpha(2) macroglobulin gene (A2M) and late-onset Alzheimer's disease (LOAD) has been recently described. We developed a PCR assay to analyze this polymorphism in 190 LOAD patients (older than 65 years) and 400 controls from Spain. Controls were stratified into three groups: <65 years (n = 200), 65 to 80 years (n = 100), and 81 years or older (n = 100). We found a significantly higher frequency of carriers of the D allele in patients older than 81 years compared to controls older than 81 years (p = 0.0012). In addition, the frequency of the D allele was significantly lower in controls older than 81 years compared to controls younger than 65 (p = 0.048). Our work suggests that the D allele confers an age-dependent increased risk to develop late-onset Alzheimer's disease.
Assuntos
Doença de Alzheimer/genética , Polimorfismo Genético , alfa-Macroglobulinas/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Alelos , Cromossomos Humanos Par 12 , Deleção de Genes , Genótipo , Humanos , Mutagênese Insercional , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVES: Several lines of evidence suggest that the endothelial constitutive nitric oxide synthase (ecNOS) and angiotensin converting enzyme (ACE) may have a role in Alzheimer's disease. ACE is widely expressed in the brain, and a DNA polymorphism at the ACE gene has been linked to the risk for late onset Alzheimer's disease. Nitric oxide (NO) production by microglial cells, astrocytes, and brain microvessels is enhanced in patients with Alzheimer's disease. There is a growing evidence that NO is involved in neuronal death in Alzheimer's disease, and the oxidative stress caused by NO in the brain could be a pathogenic mechanism in Alzheimer's disease. The objective was to determine if two DNA polymorphisms at the ecNOS and ACE genes that have been linked with different levels of enzyme expression, have some effect on the risk of developing late onset Alzheimer disease. METHODS: A total of 400 healthy controls younger than 65 years and 350 patients with Alzheimer's disease (average age 72 years) were genotyped for the ACE and ecNOS polymorphisms. To define a possible role for these polymorphisms in longevity 117 healthy controls older than 85 years were also analysed. Genomic DNA was obtained and amplified by polymerase chain reaction, and genotypes were defined following a previously described procedure. Gene and genotype frequencies between patients and controls were compared statistically. RESULTS: Gene and genotype frequencies for the ecNOS and ACE polymorphisms did not differ between both groups of healthy controls (<65 years and >85 years). EcNOS gene and genotype frequencies were similar between patients and controls. There was a slight but significantly increased frequency of the ACE-I allele among patients with Alzheimer's disease compared with controls (p=0.03; OR=1.28, 95%CI= 1.04;1.58). CONCLUSIONS: The ACE-I allele was associated with a slightly increased risk of developing late onset Alzheimer's disease.
Assuntos
Doença de Alzheimer/enzimologia , Doença de Alzheimer/genética , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Polimorfismo Genético/genética , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alelos , Apolipoproteínas E/genética , DNA/genética , Endotélio Vascular/metabolismo , Feminino , Genótipo , Humanos , Masculino , Neuroglia/metabolismo , Estresse Oxidativo/fisiologia , Reação em Cadeia da PolimeraseAssuntos
Craniossinostoses/diagnóstico , Dermatite Seborreica/diagnóstico , Transtornos de Enxaqueca/diagnóstico , Neuralgia do Trigêmeo/diagnóstico , Adulto , Doenças do Sistema Nervoso Autônomo/diagnóstico , Encéfalo/patologia , Feminino , Lateralidade Funcional , Humanos , Imageamento por Ressonância Magnética , Exame Neurológico , Crânio/patologia , SíndromeRESUMO
Los factores neurotróficos son moléculas que regulan la supervivencia neuronal, la plasticidad del sistema nervioso y otras funciones de las neuronas y células gliales, así como de algunos tejidos no nerviosos. Han sido implicados en la etiopatogenia de algunas enfermedades neurodegenerativas, y algunos de ellos han sido propuestos como agentes terapéuticos para estas enfermedades, basándose en estudios in vitro y en modelos animales. Las principales familias de factores neurotróficos con potencial terapéutico son la de las NT (NGF, BDNF y NT-3), la del GDNF, CNTF e IGF. Algunas de estas moléculas ya han sido utilizadas en ensayos clínicos con resultados contradictorios. Una de las mayores dificultades para su posible uso clínico es conseguir una liberación adecuada en el sistema nervioso central. No obstante, los datos disponibles refrendan su uso en el tratamiento de algunas patologías como la enfermedad de Alzheimer, la enfermedad de Parkinson, las neuropatías periféricas o la esclerosis lateral amiotrófica. Esta revisión recopila los aspectos esenciales de los factores neurotróficos así como su importancia clínica y potencial terapéutico. También se discuten las futuras direcciones de las próximas investigaciones (AU)
Assuntos
Animais , Humanos , Somatomedinas , Fármacos Neuroprotetores , Doenças Neurodegenerativas , Fatores de Crescimento Neural , Lesões Encefálicas TraumáticasRESUMO
Introducción: Hay un estimable número estudios de los que se analiza el curso clínico de la esclerosis múltiple (EM), sin embargo, sólo una minoría parten del momento del inicio sintomático. Se presentan una serie de pacientes diagnosticados de EM y evaluados de forma longitudinal desde el comienzo de la enfermedad. Se planteó como objetivo secundario un estudio comparativo de la incapacidad entre un grupo de pacientes tratados con inmunosupresores y aquellos que no recibieron tratamiento. Pacientes y métodos: Los pacientes fueron incluidos si disponían de un seguimiento clínico consecutivo superior a 3 años. Para su diagnóstico se utilizaron los criterios de Poser. Se calculó la incapacidad neurológica según la escala ampliada de discapacidad de Kurtzke (EDSS). Resultados: Se examinaron 55 pacientes, de los cuales 46 presentaban una forma clínicamente definida y 9 casos una forma clínicamente probable de EM. Treinta y tres enfermos tenían una forma remitente recidivante, 11 secundaria progresiva y 11 primaria progresiva. La edad media de inicio de la enfermedad fue de 31,1 años y la duración media del seguimiento clínico de 7 años. Los síntomas piramidales y sensitivos fueron las manifestaciones iniciales más comunes. El tiempo que tardaron en alcanzar un EDSS-3 y un EDSS-6 fue 4,5 y 7,5 años, respectivamente. De un total de 23 pacientes evaluados durante 10 o más años, 11 (48 por ciento) presentaban una EM benigna. El tiempo medio para llegar a una forma secundaria progresiva fue de 6 años. No hubo diferencias significativas entre el grupo tratado y los pacientes no tratados con inmunosupresores. Conclusiones: Los estudios longitudinales que parten de estadios clínicos iniciales son los más útiles para conocer la semiología, patrón clínico y pronóstico de la EM. Nuestros resultados aconsejan cautela antes de iniciar una terapia inmunosupresora o inmunomoduladora temprana (AU)