Towards establishing MS prevalence in Latin America and the Caribbean.

A very high prevalence of multiple sclerosis (MS) has been reported in some Western European and North American countries. The few surveys of MS epidemiology in South America reveal lower prevalence rates, implying that susceptibility varies between distinct ethnic groups, thus forming an important determinant of the geographic distribution of the disease. The objective of this study is to review MS prevalence estimates in different Latin American and Caribbean countries. We reviewed surveys of regional MS prevalence from 1991 to 2011. Sources included an online database, authors' reports and proceedings or specific lectures from regional conferences. We obtained a total of 30 prevalence surveys from 15 countries, showing low/medium MS prevalence rates. Both the number and the quality of prevalence surveys have greatly improved in this region over recent decades. This is the first collaborative study to map the regional frequency of MS. Establishment of standardized methods and joint epidemiological studies will advance future MS research in Latin America and the Caribbean.

Fluctuations of MS births and UV-light exposure.

BACKGROUND: Patients with multiple sclerosis (MS) are more frequently born in spring when compared to autumn. Fluctuation of UV-light has been hypothesized to drive this phenomenon. AIM: To assess the correlation between fluctuation of sunlight and birth season in persons with MS. METHODS: For this record-linkage study, we collected from the international MSBase and the Italian MS iMed-web databases the dates of birth of 11,415 patients with MS from 36 centres from 15 countries worldwide and compared these to dates of live-births from national registries. From all participating sites, we collected data on UV-light fluctuation and assessed its correlation with seasonal fluctuation in MS births. RESULTS: Compared with the reference cohort, an increased proportion of persons with MS were born in spring and a decreased proportion in autumn (odds ratio (OR) to be born in spring versus autumn = 1.158, χ² = 36.347, P < 0.001). There was no significantly increased fluctuation of MS births with increased quartile of ambient UV-light fluctuation (Ptrend = 0.086). CONCLUSION: Seasonal fluctuation of MS births as found in this worldwide cohort of patients with MS did not correlate with variation in seasonal fluctuation of UV-light. Most likely, it results from a complex interplay between fluctuation of sunlight, behavioural factors, other environmental factors and (epi)genetic factors.

Conventional brain MRI in neuromyelitis optica.

BACKGROUND AND PURPOSE: Numerous case series have demonstrated that lesions on brain MRI are common in neuromyelitis optica (NMO), but there has not been an attempt to survey and synthesize the literature on neuro-radiology of brain findings in NMO. OBJECTIVES: To review the studies on conventional brain MRI in NMO and to propose to incorporate characteristic brain MRI lesions into the diagnostic criteria of NMO. METHODS: We searched for articles with descriptions of brain MRI findings in NMO in EBSCO, EMBASE, PubMed/Medline, Science Citation Index, and SCOPUS. RESULTS: Brain abnormalities are seen in majority of NMO patients as disease duration increases. A minority of NMO patients meet Barkhof criteria for space dissemination in multiple sclerosis (MS), and these criteria should not be used to exclude NMO diagnosis. Distinctive brain lesions of NMO are cataloged and described. CONCLUSIONS: Brain lesions in NMO are a consistent feature of the disease. International consensus MRI criteria are needed for NMO analogous to the existing criteria for MS.

Multiple sclerosis and solar exposure before the age of 15 years: case-control study in Cuba, Martinique and Sicily.

Few studies report a protective role of childhood solar exposure to multiple sclerosis. Our objective was to confirm the protective role of childhood solar exposure in multiple sclerosis in Cuba, Martinique and Sicily. This was a matched case- control study, and cases met Poser criteria for clinically, laboratory (definite, probable) multiple sclerosis. Controls were resident population, without neurological disorder, living close to cases (within 100 km), matched for sex, age (+/-5 years), residence before age 15. We recruited 551 subjects during a 1-year period (193 cases, Cuba n = 95, Sicily n = 50, Martinique n = 48; 358 controls). Some (89%) met definite clinical multiple sclerosis criteria (relapsing remitting form (with and without sequel) (74%), secondary progressive (21%), primary progressive (5%)). Odds ratios in a uni-variate analysis were: family history of multiple sclerosis (5.1) and autoimmune disorder (4.0); wearing shirt (3.5), hat (2.7), pants (2.4); sun exposure causing sunburn (1.8); sun exposure duration (1 h more/day; weekends 0.91, weekdays 0.86); bare-chested (0.6); water sports (0.2). Independent factors in the multivariate analysis were family history of multiple sclerosis (4.8 (1.50-15.10)), wearing pants under sunlight (1.9 (1.10-3.20)), sun exposure duration (1 h more/ day, weekdays 0.90 (0.85-0.98), weekends 0.93 (0.87-0.99)), water sports (0.23 (0.13-0.40)). We conclude that outdoor leisure activities in addition to sun exposure reports are associated with a reduced multiple sclerosis risk, with evidence of dose response.

Relapsing neuromyelitis optica: long term history and clinical predictors of death.

BACKGROUND: Relapsing neuromyelitis optica (RNMO) is an uncommon but devastating inflammatory disorder of the central nervous system. Long term history in a wide series of RNMO is required for better knowledge of the course of the disease and identification of patients at high risk of death. METHODS: Clinical features of patients with RNMO (88 women/eight men) obtained from the geographic Caribbean database (Cuba and French West Indies) were used to determine the progression of disability and to identify clinical predictors of death. RESULTS: Median age at onset of RNMO was 29.5 years (range 11-74). Median duration of disease was 9.5 years (1-40). Median relapse rate was 0.7 attack/patient/year (0.1-3). 66 patients experienced severe visual loss in at least one eye and 46 in both eyes. Median time from onset to unilateral and bilateral severe visual loss was 3 and 15 years, respectively. Median times to reach Kurtzke Disability Status Scale 3, 6 and 8 from onset of RNMO were 1, 8 and 22 years. There were 24 deaths (25%); within 5 years in 63% of cases. A higher attack frequency during the first year of disease (p = 0.009), blindness (p = 0.04) and sphincter signs at onset (p = 0.02) and lack of recovery of first attack (p = 0.003) were independently associated with a shorter time to death. CONCLUSION: RNMO is a very rapidly disabling disease affecting primarily young women. This study has identified clinical features that predict a poor outcome. These findings suggest that early and aggressive immunotherapy might be warranted in RNMO.

Treatment with type I interferons induces a regulatory T cell subset in peripheral blood mononuclear cells from multiple sclerosis patients.

Type I Interferon (IFN-alpha/beta) therapy has altered the natural course of multiple sclerosis. In this paper we evaluate the possible molecular mechanisms involved in the in vitro effects of IFN-alpha/beta on peripheral blood mononuclear cells from patients with clinically definite Relapsing-Remitting Multiple Sclerosis. The total RNA from IFN-alpha, IFN-beta treated cells and untreated cells was extracted and amplified for CD86, CD28, CTLA-4, TNF-alpha, IFN-gamma, CCL2, CCR5, IL-13, MMP-9, TIMP-1, CD25, TGF-beta, IL-10 and the transcriptional factor Foxp3 by Reverse Transcription-Polymerase Chain Reaction and the CD4+CD25high subset was evaluated using flow cytometry. In general, there were no significant differences concerning the modulation of the genes studied in the response to IFN-alpha and IFN-beta treatments, which suggest a similar mechanism of action for both interferons. However, we found a significant increment in IFN-gamma expression after IFN-alpha but not after IFN-beta treatments. The in vitro treatment of mononuclear cells from multiple sclerosis patients with both interferons significantly increased the CD25 mRNA. Furthermore, we observed a CD25/Foxp3 correlation and an increment of the CD4+CD25high subset, indicating that the induction of regulatory T cells could be a crucial mechanism involved in the type I interferon effects.

[The influence of geographical background on the clinical and neurophysiological characteristics of patients with multiple sclerosis in Cuba]. / Influencia del origen geográfico en las características clínicas y neurofisiológicas de pacientes con esclerosis multiple en Cuba.

INTRODUCTION: Multiple sclerosis (MS) was first described by Charcot in 1868 and the first case in Cuba was reported in 1965. Prevalence rate is now considered to be about 10 cases/100,000 inhabitants. Cuba is an island that can be divided into three different geographical regions and a comparison of these areas is interesting because it is known that geographical features exert an influence on MS. Demographic differences are also present. AIMS: The purpose of this study was to evaluate a sample of cases from the Western part of the country as regards their results on two important scales and the results of evoked potentials (EP), and to compare them with two samples of patients from the other two regions. PATIENTS AND METHODS: The first sample was made up of 50 patients living in the western region; their diagnosis was confirmed, the scales were applied and the EP test was performed because of its high degree of sensitivity, objectivity and reproducibility. Results were then compared with the other two studies that had already been reported. RESULTS: Most cases had a score of between 0.5 and 5.5 points on the EDSS and only 6% scored above 7.0 points. Patients with PP type MS obtained higher scores. More than half the cases had more than 80 points on the Scripps scale and the second largest group had between 61 and 80 points; the two progressive forms behaved in a similar manner. The most sensitive EP are visual, followed by somatosensory and, lastly, by brain stem auditory EP (BAEP). The vast majority of the results compared with the series from the central region and from Santiago de Cuba were similar, yet some significant differences were found: progression time is longer in the West, EDSS scores were higher in the primary progressive form in the East and the BAEP were less sensitive in the West. CONCLUSIONS: Our findings correspond to those available from other countries around the world and it can be seen that some of the parameters differ between the three regions.

[Alpha interferon and Alzheimer's disease]. / Interferón alfa y enfermedad de Alzheimer.

INTRODUCTION: Alzheimer's disease (AD) is the commonest cause of dementia; its aetiology is unknown and there is non-specific treatment to detain the course of the disease. The interferons (IFN) are proteins which have antiviral, antiproliferative and immuno-modulating effects, and in the central nervous system these effects are mediated through the opiate receptors and the dopaminergic system. There is evidence that AD may be related to certain prion diseases and certain viruses, and that the IFN system has become deteriorated in this condition. OBJECTIVE: We present a review of patients with AD treated with alpha interferon. DEVELOPMENT: The first known case in the literature was that of a 69 year old man with definite AD (NINCDS-ADRDA) who was given alpha leucocytic IFN intrathecally and who initially was suspected of having Creutzfeldt-Jakob disease; after his treatment with IFN-alpha, his neurological signs were observed to have stabilized. Subsequently, the results of a controlled, randomized, clinical trial were analyzed for 16 patients with probable EA (NINCDS-ADRDA) treated with recombinant IFN-alpha 2b intramuscularly, in whom no changes in clinical and neurophysiological assessment were observed after a year of treatment. However, there was a significant improvement in one of the variables used to measure quality of life, together with a certain reduction in mortality in the patients treated with IFN-alpha. CONCLUSION: These results should be investigated in future studies in the light of current findings concerning the fact that, in the neurophysiological changes in AD, the pro-inflammatory cytokines, of which some of their numerous actions are blocked by IFN-alpha, may produce a deleterious effect on the course of AD.

[Alpha interferon in the treatment of multiple sclerosis. Update and experience in Cuba]. / Interferón alfa en el tratamiento de la esclerosis múltiple. Actualización y experiencia en Cuba.

OBJECTIVES: We present an update of specific treatment for multiple sclerosis (MS), especially the form with a clinical course of exacerbation-remission (ER), in which we consider the benefits of beta interferons, copolymer 1 and intravenous immunoglobulin. We discuss the properties of alpha interferon and its modes of action which are very similar to those of beta interferon. The main clinical trials in which various subtypes of alpha interferons were used are summarized. PATIENTS AND METHODS: We establish the elements which justify interest in studying this substance and present the main trials carried out in Cuba. These consist in an initial trial in 9 patients, with encouraging results in the clinical course ER-MS and following this, the findings of a preliminary study of the first 17 patients of a randomized, double-blind National Clinical Trial, in which a placebo was used for control. CONCLUSIONS: In view of these results we recommend that the study being carried out in Cuba to confirm the efficacy of alpha interferon in the ER-MS form be continued.

[Recent advances in the treatment the nervous system disorders with interferon-alpha]. / Actualización del tratamiento con interferón alfa en las enfermedades del sistema nervioso.

INTRODUCTION: The interferons (IFN) have had considerable effect on the course of relapses and the natural course of the disability of patients with multiple sclerosis (MS). However, the effects of IFN in other neurological disorders are little known. OBJECTIVES: To review the literature on the experimental and clinical applications of the IFN in disorders of the nervous system excluding MS. DEVELOPMENT: We reviewed studies of the applications of the IFN in viral diseases (experimental and human rabies, herpes zoster, herpes virus, non-herpetic meningoencephalitic viruses, HTLV-I myelopathy, arbovirus in animals, subacute sclerosing panencephalitis (SSPE), progressive multifocal leukoencephalopathy); supposedly viral diseases (Reye's syndrome), continuous partial epilepsy (Kojewnikoff's syndrome); prion diseases (Creutzfeldt-Jakob disease); degenerative-hereditary diseases (amyotrophic lateral sclerosis, Alzheimer's disease, schizophrenia, Sturge-Weber-Dimitri syndrome); immuno-allergic disorders (experimental myasthenia gravis, chronic inflammatory demyelinating polyneuropathy-CIDP-); Landry-Guillain-Barré-Strohl syndrome, polyneuropathy associated with IgM monoclonal gammapathy; tumour disorders (benign and malignant primary tumours of the brain, metastatic tumours, meningeal carcinomatosis, extra-intracranial haemangiomas, meningiomas), and other causes (cuban epidemic neuropathy, neuro-Becçet). CONCLUSIONS: Disorders of the nervous system in which IFN may be used in a clinical trial include: herpes zoster and herpes simplex infections, HTLV-I myelopathy; subacute sclerosing leukoencephalopathy, continuous partial epilepsy (Kojewnicoff's syndrome), intra-extracranial haemangiomas, CIDP, polyneuropathy associated with IgM gamma monoclonal disorder, malignant primary tumours, recurrent meningiomas, some cerebral metastases, Behçet's disease and schizophrenia.

[Clinical features of multiple sclerosis in Western Cuba. A comparison with two other regions in the country]. / Características clínicas de la esclerosis múltiple en el Occidente de Cuba. Comparación con otras dos regiones del país.

INTRODUCTION: Multiple sclerosis (MS) is an inflammatory disease in its early stages whose primary or secondary immunological mechanisms produce reversible or irreversible lesions in the myelin and axons in the central nervous system. The first case of MS in Cuba was reported in 1965. Current prevalence of MS is considered to be 10 cases/100,000 inhabitants. AIMS: The aim of this study was to characterise MS in Western Cuba from a clinical point of view and in comparison with other similar studies carried out in two other regions in the country. PATIENTS AND METHODS: 50 patients living in the western region were clinically assessed. Statistical tests were carried out to compare this survey with two similar studies conducted in the central and eastern regions. RESULTS: 80% of our patients were females, predominantly white skinned, the main events in their family histories were neurological diseases and psychiatric diseases, essentially schizophrenia, the chief triggering event being psychic tension, the most frequent form of progression was the remittent recurring form, followed by secondary progressive form, and then the primary progressive; the main symptoms at onset were visual, followed by pyramidal and sensory; the most strongly affected functional system was the pyramidal and then the sensory system; the functional systems are more affected in the primary progressive form, except the visual and the brainstem; the largest group of patients corresponded to those that had a history of over 10 years with the disorder. By far the majority of results compared with the series from the central region and from Santiago de Cuba were similar, but some significant differences did appear on comparing these two series. CONCLUSIONS: The study shows the characteristics of the disease in the Western region valuated using distinct parameters and several differences between the three series can be observed fundamentally with regard to skin colour, triggering events, symptoms at onset and functional involvement in the forms of progression.

[Sensitivity of motor evoked potentials in detecting cortico-spinal lesions in patients with multiple sclerosis]. / Sensibilidad de los potenciales evocados motores en la detección de lesiones corticospinales en pacientes con esclerosis múltiple.

INTRODUCTION: Motor evoked potentials (MEP) are very useful for the evaluation of multiple sclerosis patients. OBJECTIVE: To know the sensibility of MEP in a group of patients with diagnosis of multiple sclerosis. PATIENTS AND METHODS: A transversal and descriptive study was done in 56 patients with definite multiple sclerosis (MS). MEP using magnetic stimulation were carried out in all of them, with recordings over abductor pollicis brevis and tibialis anterioris. We analyzed the sensibility of MEP and the clinical correlation of this study. In 22 patients the sensibility of MEP and somatosensory, auditory and visual evoked potentials was compared. RESULTS: Abnormalities were detected in the 87% of records, and in 18% with absences of clinical signs of corticospinal lesion. We found statistically significant differences between relapsing-remitting form and primary chronic and progressive form (Wilk's lambda = 0.606, p = 0.00), with a high lineal relation to Kurtzke Scale (p < 0.05). In relation to the other modalities of evoked potentials, MEP were the most sensible study (68.1%), followed by somatosensory (59%), visual (45.4%) and auditory (22.5%) evoked potentials. CONCLUSIONS: MEP are a very sensible modality of evoked potentials for the detection of corticospinal lesions in MS patients, with a high degree of clinical correlation.

[Neurophysiological assessment in patients with clinically defined multiple sclerosis with special reference to P300 wave study]. / Evaluación neurofisiológica en pacientes con esclerosis múltiple clínica definida con especial referencia al estudio de la onda P300.

INTRODUCTION: In the cognitive sphere, alterations have been found in up to 65% of patients with multiple sclerosis (MS). Study of the P300 wave is a positive component of long latency related to cognitive function: amplitude with attention, and latency with the ability to process information. OBJECTIVE: To assess a study of the P300 wave in a group of patients with MS. PATIENTS AND METHODS: The P300 wave was studied in 26 patients, 22 women and 4 men, with definite clinical MS (on criteria of Poser et al), with normal motor and sensory conduction velocity studies. All patients had a battery of multi-modal evoked potentials (MEP), nuclear magnetic resonance imaging and immunological study of the cerebrospinal fluid. Seventeen patients had the exacerbation-remission (ER) and nine the primary progressive (PP) clinical forms of the disorder. RESULTS: The most markedly altered MEP were the visual and somatosensory evoked potentials (SSEP) of the patients with MS. When the types of clinical course were compared, the SSEP were statistically significant in the PP form, which may be explained by the greater spinal involvement of these patients. Comparative analysis of the P300 wave was done for 26 healthy patients of similar age and sex to that of the patients, and significant differences were found in P300 latency and amplitude between the MS and control groups. The patients who had had the disease for longer had significantly greater anomalies in the P300 waves. CONCLUSION: Study of the evolution of the P300 wave, which is cheap and easy to do, may be valuable in the evolutional assessment of cognitive changes in patients with MS.

[Interferon-alpha2b recombinant improved the cognitive dysfunction in patients with relapsing remitting multiple sclerosis]. / El interferón-alpha2b recombinante mejora la disfunción cognitiva en pacientes con esclerosis múltiple.

INTRODUCTION: Some experimental, Phase II clinical trials and the preliminary reports of the Cuban Phase III clinical trial indicate that alpha-IFN (IFN) may be useful in relapsing remitting (RR) multiple sclerosis (MS). The reports in Cuba showed that 70% of the MS patients have cognitive dysfunction. OBJECTIVE: To assess the efficacy of IFN-alpha2b recombinant in the cognitive dysfunction of RR MS. PATIENTS AND METHODS: 57 RR-MS clinical definite patients from the randomised, double blind, placebo controlled study of 225 patients with RR-MS and brain MRI confirmed. Patients were randomly assigned to receive intramuscular IFN-alpha2b (Heberon R) 10 million IU (high dose), 3 million IU (low dose) or placebo twice week for 2 years. Outcome results were blinding evaluated considering changes in the following tests: Luria, WAIS, Benton and PASAT-3. Adverse events and side effects were not evaluated to maintain physician blinding. RESULTS: The initial comparison of the groups did not show any differences among the placebo (n=20), low dose (n=18) and high dose (n=19) considering age (p=0.234), gender, ethnic group (p=0.012), years ill (p=0.787), EDSS (p=0.203) and rate of relapses (p=0.432). The Luria's Test showed an improved in the low dose group from 2.50 +/- 1.34 to 1.39 +/- 1.85 (p=0.029) and in the high dose group from 3.22 +/- 1.89 to 2.17 +/- 1.50 (p=0.006) vs placebo 2.85 +/- 1.66 to 2.90 +/- 1.97 (p=0.723). The results of the Benton's test demonstrated that the low dose group had an improved from 5.50 +/- 1.10 to 6.22 +/- 1.31 (p=0.047), in the high dose group from 4.87 +/- 1.85 to 5.78 +/- 1.35 (p=0.005) where as in the placebo group worse from 5.15 +/- 1.76 to 5.05 +/- 2.11 (p=0.893). The WAIS test showed the same results, the low dose group increased from 5.17 +/- 1.34 to 6.06 +/- 1.21 (p=0.022), the high dose group from 4.56 +/- 1.38 to 5.39 +/- 1.29 (p=0.007) and the placebo group worse from 5.25 +/- 1.25 to 5.05 +/- 1.57 (p=0.354). Finally, the PASAT-3 test increased in the IFNs groups: from 45.72 +/- 10.61 to 49.94 +/- 11.68 (p=0.015) in the low dose group, from 42.67 +/- 11.04 to 48.72 +/- 8.84 (p=0.03) in the high dose group, but in the placebo group worse from 44.55 +/- 10.86 to 41.95 +/- 13.74 (p=0.655). CONCLUSION: IFN-alpha improved the cognitive dysfunction in RR-MS patients. The higher dose is more beneficial.

[Clinical characterization of patients with multiple sclerosis defined in Cuba]. / Caracterización clínica de pacientes con esclerosis múltiple definida en Cuba.

INTRODUCTION: Since 1975 no studies have been done in Cuba defining the clinical characteristics of patients with multiple sclerosis (MS). OBJECTIVE: To describe the characteristics of a group of Cuban patients with definite clinical MS. MATERIAL AND METHODS: Fifty eight patients with definite clinical MS were studied (Poser et al) with normal motor (VCM) and sensory (VCS) conduction velocities. Tests were done on them: clinical scale (Scripps), incapacity (EDSS) and quality of life (Steps), together with various complementary tests. Each patient was classified according to the way in which the disease evolved. Also the two commonest clinical types were compared and we applied the difference test between percentages of non-paired samples with an alfa level of 0.05. RESULTS: Onset of the illness in most cases was before the age of 40 (86.1%), 75.9% were women and 82.8% were white. In 15.3% there was a family history of MS. In 25.9% there were psychiatric disorders and trigger factors (43.1%. The most frequent initial symptoms were pyramidal (48.3%) sensorial (41.4%) and cerebellar (39.7%). Scripps scale scores were < 80 in 60.2%, in EDSS < 5 (61.9%) and in the Clinical Steps < 3 in 65.4%). Motor potentials (81.9%) somatosensory potential (PESS) (72.3%) and magnetic resonance imaging (MR) (76.4%) were the most abnormal results. Exacerbation-remission (ER) was the most frequent type of evolution (53.4%) generally affecting patients aged under 40 years old (p = 0.02), EDSS < 5 (64.4%), Scripps > 80 (61.2%), Steps < 3 (95.6%), pyramidal system involvement (58.5%), cerebellar (29.2%) and MRI abnormality (80%). The progressive primary form (PP) was the second most frequent (29.3%); 29.4% were under 40 years of age, had more marked changes in all functional system (100%), degree of incapacity and quality of life (100%). PESS (92.5%); the urodynamic tests 58.85%) were less positive on MRI (54.5%) as compared with the ER form. CONCLUSIONS: The differences found between the clinical forms ER and II indicate that there is greater deterioration in the PP form, probably due to age and more cerebellar and spinal cord involvement.

[A severe episode in a patient with recurrent disseminated acute encephalitis due to vaccination against hepatitis B. For or against vaccination?]. / Brote grave en paciente con encefalitis aguda diseminada recurrente por vacuna contra LA hepatitis B: A favor o en contra de la Vacunación?

INTRODUCTION: Several reports of new cases of CNS demyelination or reactivation of MS after hepatitis B vaccination have raised the possibility of a causal relationship. Conversely, some authors have concluded that the risk of developing a demyelinating CNS event after a hepatitis B vaccination is unknown. PATIENTS AND METHODS: We have observed a 40 year old man, with diabetes mellitus (DM) type 1 and a previous history of recurrent acute demyelinating encephalomyelitis (rADEM). The patient had experienced three episodes of neurological dysfunction and he fulfilled the criteria for definite clinical MS but MRI showed demyelinating lesions in the pons and cerebellum without MRI criteria of MS. CSF analysis showed oligoclonal banding. The patient had been clinically stable during the last 6 years. Yearly MRI during this period had not shown any new disease activity. He was admitted in our MS Clinic due to dizziness, nausea, vomiting and diplopia, 6 weeks after the first of the two injections for hepatitis B vaccine after participating in the national programme of vaccination in DM type 1 patients. Clinical examination showed intranuclear ophtalmoplegia, visual loss in the left eye and worsening of the previous cerebellar and pyramidal signs. MRI showed an increase in the old lesions with high intensity signals on T2 weighted sequences with post gadolinium enhancement on T1 weighted sequences located in the brainstem and mesencephalon. The patient s diabetes mellitus deteriorated with ketoacidosis that needed increased doses of insulin. His condition worsened and he developed partial motor seizures. He improved 15 days later but he still had involvement of the cerebellar and pyramidal systems and occasional dizziness. CONCLUSIONS: As pointed out by some authors and in view of this observation, it would seem reasonable, as a precautionary measure, to avoid hepatitis B vaccination in patients with a personal or family history of symptoms suggestive of a demyelinating disease of the CNS.

[Exogenous factors in the aetiology of multiple sclerosis in Cuba. A study of cases and controls]. / Factores exógenos en la etiología de la esclerosis múltiple en Cuba. Estudio de casos y controles.

INTRODUCTION: Descriptive epidemiological studies indicate that the prevalence of multiple sclerosis (MS) in Cuba is in the mid range of risk. It is not known what exogenous factors may be related to the aetiology of MS. OBJECTIVE: To study the exogenous factors possibly related to the aetiology of MS in the central provinces of Cuba. PATIENTS AND METHODS: We studied all the patients with definite clinical MS (Poser et al) with positive MR who came from the provinces of Cienfuegos, Villa Clara and Sancti Spiritus. The protocol was approved by the Medical Ethics Committees of each of the three institutions and reviewed by two international authorities on the subject. Each of the patients (cases) and one member of their family (control), after written consent, when they fulfilled the criteria for inclusion in the study, were personally interviewed by trained persons and the questionnaire for studying cases and controls of Boiko et al was completed. The questionnaire had been adapted for use in Cuba. The main data obtained were: demographic data, history of occupation and residence, personal medical history, exposure to possibly toxic substances, diet and nutrition, contact with animals and life style. For measurement of risk we used the risk of the results of the crossed products odds ratio (OR) with its confidence interval (CI), always insisting on precision of 95%. RESULTS: High educational level (OR= 2.293; 95% CI= 0.9 5.4), two or more children (OR= 2.84; 95% CI= 1.22 6.59), four or more pregnancies (OR= 3.60; 95% CI= 0.69 18.7), three or more deliveries (OR= 1.939, 95% CI= 0.44 8.4); previous measles infection (OR= 2.042; 95% CI= 0.76 5.47), a history of migraine (OR= 2.538; 95% CI= 0.81 7.94); stress (OR= 3.768; 95% CI= 1.64 8.62) and insomnia (OR= 2.95; 95% CI= 1.14 7.14) were the factors related to MS. CONCLUSIONS: This study confirmed the existence of exogenous factors in the aetiology of patients with clinically defined MS and positive MR findings who lived in the provinces studied in Cuba. The exogenous factors found in this population of patients with MS were: high educational level, two or more children, four or more pregnancies, three or more deliveries, previous measles, a history of migraine, stress and insomnia.

[Actual status of multiple sclerosis in Cuba. National cooperative group for the clinical trial "Recombinant interferon alpha-2b in multiple sclerosis"]. / Estado actual de la esclerosis múltiple en Cuba. Grupo Cooperativo Nacional para el Ensayo Clínico 'Interferón alfa-2b recombinante en la esclerosis múltiple'.

INTRODUCTION: Multiple sclerosis (MS) has been considered to be an uncommon disorder in Cuba. In recent years many Cuban investigators have worked hard studying MS in Cuba. DEVELOPMENT: We review the history, epidemiology, clinical characteristics, complementary investigations and clinical trials of recent studies published in national and international journals on the most important investigations done on MS in Cuba. There is an outstanding placebo-controlled, double blind, multicentric randomised clinical trial using recombinant alpha 2b-IFN in the relapsing-remitting clinical form in which the results obtained in the first 30 patients who completed 2 years treatment show a statistically significant reduction in the frequency of relapses and the number of patients free of relapses in patients who received alpha-IFN as compared with those given placebo treatment. CONCLUSIONS: There has been an increase in the number of studies made on MS in Cuba in the past two years. Numerous clinical, neuroepidemiological, neurophysiological, biochemical, immunological, imaging and neuropsychological investigations and clinical trials indicate a marked increase in understanding of MS. The results of all these studies indicated the need for the creation of a National Reference Centre for Patients with Multiple Sclerosis, due to the complexity of this type of patients and the need to offer improved medical attention from a specialist team and to integrate the investigations in Cuba and internationally so as to reach the level of more developed countries.

[Clinical characteristics of the peripheral form of epidemic neuropathy in the province of Cienfuegos]. / Características clínicas de la neuropatía epidémica, forma periférica, en la provincia de Cienfuegos.

INTRODUCTION: From October 1992 to September 1993 clinical observations of the civil population of Cienfuegos revealed the presence of epidemic neuropathy (EN) reaching about 2,000 patients. The clinical manifestations were not uniform. Although numerous studies have been carried out in our country, none have established the characteristics of EN 'the peripheral form'. MATERIAL AND METHODS: We studied the first 50 patients assisted by the neurological services of the clinical surgical hospital Dr. Gustavo Aldereguia Lima of Cienfuegos diagnosed of EN 'peripheral form' according to the procedure established by Ministry of Public Health of Cuba. A clinical history was made for each patient consisting of: General data, history of toxic, nutritional, malabsorption factors and chronic illnesses; symptoms and a neurological examinations. Laboratory test, in a group of patients, were done in sera, urine, cerebrospinal fluid (CSF), gastric juice and neurophysiological studies that included computerized evoked potentials and electroencephalograms registers. RESULTS: Upon analysis of the clinical history, nutritional factors was common to all the patients associated to toxic and malabsorption. The clinical forms were neuropathy (NP) 48%, myeloneuropathy (MNP) 42% and myelopathy (MP) 10%. Retrobulbar optic neuropathy was observed in 42% of the patients and auditory neuropathy in 22%. CONCLUSIONS: The clinical characteristics of NP, in our cases, indicated that this disease fundamentally affects the sensorial neurons and the sensitive peripheral nerves, bilaterally, symmetrically, distally and predominantly in lower limbs. The pathological process has been associated with a distal axonopathy. However, clinic signs of myelopathy can be found up to 40% frequently combined with neuropathy or in isolated form, and seems to affect the posterior and lateral columns of the spinal cord, mainly at thoraciclumbar level. Neuropathy of central nervous system is unknown since no patient has died of EN.

Neuromyelitis optica unique area postrema lesions: nausea, vomiting, and pathogenic implications.

OBJECTIVE: To characterize the neuropathologic features of neuromyelitis optica (NMO) at the medullary floor of the fourth ventricle and area postrema. Aquaporin-4 (AQP4) autoimmunity targets this region, resulting in intractable nausea associated with vomiting or hiccups in NMO. METHODS: This neuropathologic study was performed on archival brainstem tissue from 15 patients with NMO, 5 patients with multiple sclerosis (MS), and 8 neurologically normal subjects. Logistic regression was used to evaluate whether the presence of lesions at this level increased the odds of a patient with NMO having an episode of nausea/vomiting. RESULTS: Six patients with NMO (40%), but no patients with MS or normal controls, exhibited unilateral or bilateral lesions involving the area postrema and the medullary floor of the fourth ventricle. These lesions were characterized by tissue rarefaction, blood vessel thickening, no obvious neuronal or axonal pathology, and preservation of myelin in the subependymal medullary tegmentum. AQP4 immunoreactivity was lost or markedly reduced in all 6 cases, with moderate to marked perivascular and parenchymal lymphocytic inflammatory infiltrates, prominent microglial activation, and in 3 cases, eosinophils. Complement deposition in astrocytes, macrophages, and/or perivascularly, and a prominent astroglial reaction were also present. The odds of nausea/vomiting being documented clinically was 16-fold greater in NMO cases with area postrema lesions (95% confidence interval 1.43-437, p = 0.02). CONCLUSIONS: These neuropathologic findings suggest the area postrema may be a selective target of the disease process in NMO, and are compatible with clinical reports of nausea and vomiting preceding episodes of optic neuritis and transverse myelitis or being the heralding symptom of NMO.