After the first description of TSP/HAM in 1985 and the elaboration of WHO's diagnostic criteria in 1988, the experience of the professionals in this field has increased so that a critical reappraisal of these diagnostic guidelines was considered timely. Brazilian neurologists and observers from other countries met recently to discuss and propose a modified model for diagnosing TSP/HAM with levels of ascertainment as definite, probable, and possible, according to myelopathic symptoms, serological findings, and/or detection of HTLV-I DNA and exclusion of other disorders.
The first description of the human T-lymphotropic virus type 1 (HTLV-1) was made in 1980, followed closely by the discovery of HTLV-2, in 1982. Since then, the main characteristics of these viruses, commonly referred to as HTLV-1/2, have been thoroughly studied. Central and South America and the Caribbean are areas of high prevalence of HTLV-1 and HTVL-2 and have clusters of infected people. The major modes of transmission have been through sexual contact, blood, and mother to child via breast-feeding. HTLV-1 is associated with adult T-cell leukemia/lymphoma (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and HTLV-associated uveitis as well as infectious dermatitis of children. More clarification is needed in the possible role of HTLV in rheumatologic, psychiatric, and infectious diseases. Since cures for ATL and HAM/TSP are lacking and no vaccine is available to prevent HTLV-1 and HTLV-2 transmission, these illnesses impose enormous social and financial costs on infected individuals, their families, and health care systems. For this reason, public health interventions aimed at counseling and educating high-risk individuals and populations are of vital importance. In the Americas this is especially important in the areas of high prevalence.
A high human T-cell lymphotropic virus type 1 (HTLV-1) proviral load is described in HTLV-1-associated diseases, especially HAM/TSP. However, the cut-off value to define high levels of HTLV-1 proviral load is not well established. 281 HTLV-1-infected patients from the HTLV reference center in Salvador, Brazil, were followed from 2005 to 2008. Patients were classified as asymptomatic, possible-, probable-, and definite-HAM/TSP, in accordance with diagnostic criteria proposed by De Castro-Costa et al. (2006): AIDS Res Hum Retroviruses 22:931-935. HTLV-1 proviral load was determined using real-time PCR. A receiver operator characteristic (ROC) curve was constructed using only asymptomatic individuals and definite-HAM/TSP patients. The ROC curve was used to predict the proviral load level that differentiates these two groups. Out of 281 patients, 189 were asymptomatic and 92 were diagnosed with HAM/TSP (22 possible, 23 probable, 47 definite). The mean HTLV-1 proviral load was higher in possible- (89,104 ± 93,006 copies/106 PBMC), -probable (175,854 ± 128,083 copies/106 PBMC), and definite-HAM/TSP patients (150,667 ± 122,320 copies/106 PBMC),when compared to asymptomatic individuals (27,178 ± 41,155 copies/106 PBMC) (P < 0.0001). A comparison of all HAM/TSP groups showed the highest proviral loads in probable-HAM/TSP patients, yet the differences in mean values were not statistically significant. The ROC curve suggested a value of 49,865 copies/106 PBMC, with 87% sensitivity (95% CI ¼ 74-95) and 81% specificity (95% CI ¼ 75-86), as the best proviral load cut-off point to differentiate definite HAM/TSP patients from asymptomatic individuals. HTLV-1 proviral loads are higher in groups of infected patients with eurological symptoms and may represent a relevant biological marker of disease progression.
To study the epidemiology of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Brazil, we conducted a nationwide survey between March 1994 and April 1995. Five centers from three regions of the country participated, enrolling 163 patients. Most patients came from the northeastern and southeastern regions (93.2%). Most enrollees were white women, 42.9% and 64.4%, respectively. The most common risk factors for infection included a history of venereal diseases (30.6%) and blood transfusion (21.6%). The median age at the beginning of the disease was 42 years. The main neurologic findings were spastic paraparesis, widespread brisk tendon jerks, bilateral Babinski's sign, and bladder dysfunction. Some interregional differences reached statistical significance. The ratio of females over males increased from south to north. In addition, in both southern and southeastern regions, whites prevailed, whereas in the northeast, mulattos predominated. This follows the normal distribution of the population in these regions. A significantly higher rate of venereal diseases was found in the southeast compared with the other regions studied. A history of intravenous drug use was more frequent among patients as the sample moves south. Finally, a fluctuating course of the disease was proportionally more frequent in the southern region.
-We report on the clinical characteristics of amyotrophic lateral sclerosis (ALS) in Fortaleza (Northeastern Brazil). For this, we analyzed retrospectively (from 1980 to 1999) 78 cases of ALS from the Service of Neurology of the University Hospital of Fortaleza diagnosed clinically and laboratorially (EMG, muscle biopsy, myelography, blood biochemistry, muscle enzymes and cranio-cervical X-ray). The results showed that they were mostly sporadic ALS (76/78), and they were divided into definite (n= 36), probable (n= 20), possible (n= 15) and suspected (n= 7), according to the level of diagnostic certainty. They were also subdivided into juvenile (n= 17), early-onset adult (n= 18), age-specific (n= 39) and late-onset (n= 4) groups. Clinically, they presented as initials symptoms, principally, asymmetrical (30/78) and symmetrical (24/78) weakness of extremities, besides bulbar signs, fasciculations, and atrophy. Curiously, pain as first symptom occurred in an expressive fashion (17/78). The predominant initial anatomic site, in this series, was the spinal cord, and mainly affecting the arms. As to the symptom accrual from region to region, this occurs more quickly in contiguous areas, and fasciculations are predominant when bulbar region was associated.KEY WORDS: ALS, sporadic, early-onset, pain, anatomy, symptom accrual, fasciculations. Esclerose lateral amiotrófica: análise clínica de 78 casos de Fortaleza (Nordeste Brasileiro)RESUMO -Descrevemos as características clínicas da esclerose lateral amiotrófica (ELA) em Fortaleza (Nordeste Brasileiro). Para isso, fizemos uma análise retrospectiva (de 1980 a 1999) de 78 casos de ELA do Serviço de Neurologia do Hospital Universitário de Fortaleza, diagnosticados do ponto de vista clínico e laboratorial (EMG, biópsia de músculo, mielografia, análises hematológica e bioquímica, e raio X da junção crânio-cervical). Os resultados mostraram que esses casos eram principalmente da forma esporádica (76/78), e estes foram divididos, de acordo com o nível de certeza diagnóstica, em definidos (n= 36), prováveis (n= 20), possíveis (n= 15) e suspeitos (n= 7). Eles foram também subdivididos nos grupos juvenil (n= 17), adulto jovem (n= 18), idadeespecífico (n= 39) e tardio (n= 4). Clinicamente, os principais sintomas iniciais foram fraqueza assimétrica (38/ 78) e simétrica (24/78) das extremidades, além de sinais bulbares, fasciculações e atrofia. Curiosamente, dor como sintoma inicial ocorria de maneira expressiva (17/78). O local anatômico inicial predominante foi, nessa série, a medula espinhal, afetando principalmente os braços. O avanço regional de sintomas ocorreu mais rapidamente em áreas contíguas, e as fasciculações eram predominantes quando a região bulbar estava associada. PALAVRAS-CHAVE: ELA, esporádica, início precoce, dor, anatomia, avanço dos sintomas, fasciculações.Amyotrophic lateral sclerosis (ALS) is a condition of undetermined cause, which affects the anterior horn cells and the corticospinal tract.The etiology is manifold so that different causes have been...
Objective-The effect of zinc and glutamine on brain development was investigated during the lactation period in Swiss mice.Methods-Malnutrition was induced by clustering the litter size from 6-7 pups/dam (nourished control) to 12-14 pups/dam (undernourished control) following birth. Undernourished groups received daily supplementation with glutamine by subcutaneous injections starting at day 2 and continuing until day 14. Glutamine (100 mM, 40-80μl) was used for morphological and behavioral studies. Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams. Synaptophysin (SYN) and myelin basic protein (MBP) brain expressions were evaluated by immunoblot. Zinc serum and brain levels and hippocampal neurotransmitters were also evaluated. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.FVLD, AABLD, and AAMCR contributed with the stereological studies. SBCC, BPC, ICC, BBO, and CMCC contributed with the behavioral studies AAML, RLG, and RBO contributed with the study design, study analysis and manuscript preparation GAM and CECM contributed with neurochemical and zinc measurements. NIH Public Access Author ManuscriptNutrition. Author manuscript; available in PMC 2011 June 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptResults-Zinc with or without glutamine improved weight gain as compared to untreated, undernourished controls. In addition, zinc supplementation improved cliff avoidance and head position during swim behaviors especially on days 9 and 10. Using design-based stereological methods, we found a significant increase in the volume of CA1 neuronal cells in undernourished control mice, which was not seen in mice receiving zinc or glutamine alone or in combination. Undernourished mice given glutamine showed increased CA1 layer volume as compared with the other groups, consistent with the trend toward increased number of neurons. Brain zinc levels were increased in the nourished and undernourished-glutamine treated mice as compared to the undernourished controls on day 7. Undernourished glutamine-treated mice showed increased hippocampal GABA and SYN levels on day 14.Conclusion-We conclude that glutamine or zinc protects against malnutrition-induced brain developmental impairments.
-Objective: Tropical Spastic Paraparesis/HTLV-I Associated Myelopathy (TSP/HAM) is a chronic myelopathy, and pain has been mentioned as a frequent sensory symptom in this condition. The authors aimed at analyzing this symptom in a TSP/HAM patients series. Method: For this, 46 patients were analyzed considering demographic and clinical characteristics and complaint of pain as to verbal description, time of onset and classification, correlated with the degree of motor disability and type of pain. Results: Among the 46 TSP/HAM patients, 28 (60.8%) complained of pain, predominant in the early phase of the disease. Most of the patients exhibited neuropathic characteristics of pain, correlated with increased motor disability. Conclusion: Pain in TSP/HAM patients is a frequent and early symptom, and the neuropathic type is predominant (57.1%) and paralleled with increased incapacitation. The pathogenic involvement of cytokines may possibly be involved in the meaning of this symptom in this condition.Key wordS: TSP/HAM, HTLV-I, pain, inflammatory nociceptive and neuropathic, cytokines.dor em pacientes com paraparesia espástica tropical/mielopatia associada ao HTlV-i resumo -Objetivo: A Paraparesia espástica Tropical/Mielopatia Associada ao HTLV-I (PeT/MAH) é uma mielopatia crônica, e a dor tem sido mencionada como um sintoma sensitivo freqüente nessa condição. os autores objetivam analisar esse sintoma numa série de pacientes com PeT/MAH. Método: Para isso, 46 pacientes foram analisados considerando características demográficas e clínicas, e queixa de dor do ponto de vista da descrição verbal, tempo de início e classificação, correlacionados com o grau de incapacitação motora e o tipo de dor. Resultados: dentre os 46 pacientes com PeT/MAH, 28 (60,8%) se queixavam de dor, predominando na fase inicial da doença. A maioria dos pacientes evidenciou características de dor neuropática, correlacionada com aumento da incapacitação motora. Conclusão: A dor em pacientes com PeT/MAH é um sintoma freqüente e inicial, sendo o tipo neuropático predominante (57,1%) e em paralelo com maior incapacitação. o envolvimento patogênico das citocinas poderá possivelmente estar relacionado com o significado desse sintoma nessa condição clínica.PALAVrAS-CHAVe: PeT/MAH, HTLV-I, dor, nociceptiva inflamatória e neuropática, citocinas.
-Since anticonvulsants have been used for treating neuralgias, an interest has arisen to experimentally test vigabatrin for its gabaergic mechanism of action. For this, 41 Wistar rats were used, and in 25 of them a constrictive sciatic neuropathy was induced (Bennet & Xie model). For testing pain symptoms, spontaneous (scratching) and evoked behaviors to noxious (46 o C) and non-noxious (40 o C) thermal stimuli were quantified. Moreover, a comparative pharmacological study of vigabatrin with other analgesic anticonvulsant drugs was also performed. The results showed a possible dose-dependent analgesic effect of vigabatrin (gamma-vinyl-GABA) on experimental neuropathic pain, as shown by the significant (p<0.05) decreasing effect of vigabatrin on scratching and by its significant (p<0.05) increasing effect on the latency of the right hindpaw withdrawal of the animals to noxious thermal stimulus. This was corroborated by similar findings with analgesic anticonvulsants (carbamazepine, phenytoin and valproic acid). This possible and not yet described analgesic effect of vigabatrin seems not to be opioid mediated.KEY WORDS: vigabatrin, experimental, neuropathic pain, scratching behavior, thermal tests, Wistar rats, analgesia. Possível efeito analgésico da vigabatrina na dor neuropática crônica experimental animalRESUMO -O uso de anticonvulsivantes no tratamento de neuralgias despertou um interesse em testar novas drogas anticonvulsivantes, e dentre essas a vigabatrina por possuir mecanismo de ação gabaérgico. Para isso, foram usados 41 ratos Wistar e em 25 deles induziu-se neuropatia ciática constritiva (modelo de Bennett & Xie). Para testar sintomas de dor, foram quantificados comportamentos espontâneos (coçar-se) e evocados, por meio de estímulos térmicos nocivos (46 o C) e não-nocivos (40 o C). Além disso, realizou-se estudo comparativo da vigabatrina com outros anticonvulsivantes analgésicos. Os resultados mostraram um possível efeito analgésico, dose-dependente, de vigabatrina (gama-vinil-GABA) em dor neuropática experimental. Isso foi evidenciado pela diminuição significativa (p<0,05) do comportamento de coçar-se e pelo aumento significativo (p<0,05) da latência de retirada da pata posterior direita a estímulos térmicos nocivos. Isso foi corroborado por achados semelhantes em experimentos com anticonvulsivantes (carbamazepina, fenitoína e ácido valpróico) analgésicos. Esse possível efeito analgésico da vigabatrina (ainda não descrito na literatura) não é mediado pelo sistema opióide. PALAVRAS-CHAVE: vigabatrina, experimental, dor neuropática, comportamento de coçar-se, testes térmicos, ratos Wistar, analgesia.The treatment of chronic neuropathic pain is varied and only partially effective 1 . Davies et al.2 have reported on the use of anticonvulsant and antidepressive drugs in the treatment of chronic neuropathic pain. The anticonvulsant drugs are able of reverting or avoiding seizures. These drugs act by decreasing the neuronal response to seizures-inducing stimuli. Since it is known that in neuropathi...
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