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CUBAN MEDICAL LITERATURE International Workshop on
The International Workshop on Epidemic Neuropathy in Cuba was held at the Havana Convention Center from July 12th to 15th, 1994. Cuban President Fidel Castro attended the plenary session that opened this meeting and accompanied us throughout the workshop. The background and objectives of this workshop were put forward in the welcome speech given by the First Vice-Minister of Public Health, Dr. Abelardo Ramírez. He emphasized the complex nature of the epidemic and the multidisciplinary, cross sector and collaborative character of the research carried out. He explained this meeting was necessary to integrate all the experiences and results gathered, urging us to carry out rigorous scientific work sessions. He noted that although definitive results would not be obtained, we would still be able to analyze in depth the results obtained so far. Dr. Carlyle Guerra de Macedo, Director of the Pan American Health Organization (PAHO), delivered the opening speech. He stated this would probably be his last official activity in Cuba as director of the organization. He emphasized the excellent relations, cooperation and deep ties of friendship he experienced with our country during his office. He referred to the great significance of this workshop, as well as to the cost and suffering the epidemic had meant for our country. He pointed out it was an excellent opportunity to express the communion of principles and objectives of health workers and scientists working in related activities all over the world, which overcomes difficulties imposed by the global political situation. He described as extraordinary the response to Cuba’s request for collaborative work to confront this problem, and urged that the solidarity initially expressed be maintained and increased. The plenary session began with a wide and detailed conference including, briefly, the main issues and management of the epidemic in Cuba. Several experiences of epidemic management in the provinces were presented as well. Thereafter, a series of ideas was presented based on different hypotheses on the role of vitamins in the development of the epidemic and of vitamin therapy in reducing its incidence. The presence of toxic substances related to the epidemic was also discussed. Participants highlighted the special protection of priority groups - children, seniors and pregnant women. Data on the present state of the 50,945 patients reported by the end of May 1994 were presented. The illness was controlled in 85.9% of the patients, 87.2% of those with optical neuropathy, and 84.4% with peripheral neuropathy. During the afternoon, sessions were held in three work groups: clinical-therapeutic, toxic-nutritional and virological. The main papers presented at the workshop were analyzed in the groups, as well as the research results related to the subjects discussed. Clinical-Therapeutic Group This group debated aspects related to the characterization of the disease. The fundoscopic and electrophysiological findings in optical neuropathy and the clinical neurological, physiopathological and systemic symptoms of peripheral neuropathy were summarized. The anatomo-pathological and neurophysiologic results were presented. The pathogenic outline of the damage was explained. The session concluded with a summary of the multi-center controlled therapeutic trials. Due to the similarity of the clinical picture and the fundoscopic appearance to Leber’s optic neuropathy, an inherited mitochondrial disease, a DNA study was carried out by Wallace et al. on a group of these patients and their controls, looking for the mutations in this neuropathy. They concluded that there was no relation between the epidemic neuropathy and this disease. Peripheral neuropathy includes all clinical symptoms, except those dependent on the lesion of the optical nerve. The fundamental symptom was general irritation, along with irritability and passivity, which marked the beginning of the clinical picture early on. In the groups with visual and peripheral neuropathy, a short-term memory problem was found. The uniformity of the morphological lesions described in patients with different clinical pictures suggests that all the clinical types correspond to a common pathogenic mechanism. In the material studied, there are no elements indicating an inflammatory or infectious cause. The morphological changes correspond to an axon type of neuropathy, similar to the one observed in toxic-metabolic, or nutritional deficiency processes, with changes in the myelin sheath, probably of a secondary nature. A basic treatment of vitamins and, in severe cases, of hydroxocobalamin is recommended. Patients with unsatisfactory evolution merit in-depth study to determine the existence of individual predisposing factors, toxic habits, or other risk elements that may explain this response; epidemiological control involving primary care is also required. Virology Group In the virology group, the main report was presented with results obtained by Cuban institutions; participants also debated illustrative lectures related to the subject. Certain similarities between the Japanese and the Cuban epidemic were shown. Researchers from the Pedro Kourí Institute of Tropical Medicine (IPK, according to the acronym in Spanish), the Center for Genetic Engineering and Biotechnology (CIGB), and Labor 1 presented 15 papers. They all showed the unquestionable presence of viral agents (Coxsackie A9, IMV) and an agent that was not classified, but that produced a slow cytopathogenic effect. Results obtained by three Cuban laboratories working independently coincided almost completely. There were clear virological, serological, molecular, electron microscopy and pathological evidence in human samples, demonstrating the unmistakable presence of viral agents involved in the epidemic neuropathy. Samples taken from laboratory animals showed the same results. Antibodies that recognize Coxsackie A9 virus have been detected in apparently healthy populations, which speak in favor of its increasing circulation during the last years. It was concluded that:
The cause of epidemic neuropathy was considered multifactorial. Furthermore, there was no contradiction with the presence of toxic-nutritional and metabolic factors since there are many interrelating elements between these and the appearance of infections in humans. Besides, certain deficiencies in the host may trigger the virulence of viral agents. The group considers that, despite the apparent contradictions, we may be facing new situations, and that the presence of viruses in most patients forces us to consider them as a co-factor in the cause of epidemic neuropathy. Toxic-Nutritional Group In the roundtable of the toxic-nutritional group, the main work carried out by participating institutions was presented, including a summary of the different epidemiological studies performed and the main results. These showed that major associations were found with diet-related factors; smoking was found to be an important risk factor. They analyzed how the disappearance of the socialist bloc and the worsening of the U.S. embargo critically reduced food supplies since 1990, and how this was more evident in the western provinces, even though historically the eastern provinces had lower consumption levels. The diet study showed a major effect on food consumption, a less varied diet, a smaller body mass index and greater loss of body weight. The main findings of the PAHO-Ministry of Public Health-CDC study carried out in Pinar del Río were presented (see Abstract). Their analysis demonstrated that the patients consumed less meat, milk products, cereals, eggs and leafy vegetables than the control group. Nutrients and energy consumption, animal proteins, animal fats, methionine, retinol and all the vitamins in the B complex were lower in patients than in the control group. Cigar and cigarette smoking is the most important risk factor in these analyses. Eating yucca [cassava, eds] is a risk factor only in energy-adjusted models. Although it may have a direct effect, an alternative explanation is that it is a marker of a diet pattern associated with risk. Several nutritional factors were protective. Lycopene and other carotenoids having antioxidant effects displayed a very strong protective association. The administration of B complex vitamins, especially riboflavine and nutrients associated with consumption of animal products, gives strong protection, but as they are interrelated, it is difficult to separate their effects. Biochemical tests showed much higher serum creatinine levels in the urine of the patients than the controls; lower serum levels of alpha carotenoids, lycopene, beta carotenes, cryptoxanthins and selenium were found in the patients than in control groups. The results of ecological studies carried out in Pinar del Río were also shown. They indicated that rural areas with high disease rates had a higher population density, substantial state tobacco production with little land access for production of food to complement limited food supplies, and a monotonous carbohydrate-based diet. The adjacent areas with low disease rates were less populated, had private-farms or aquaculture. They sold their surplus in the market and had a less monotonous diet. At the same time, significantly higher disease rates were confirmed in areas dominated by state tobacco plantations as compared to areas with mainly private farms, after population density stratification. After temporal and social distribution was explained, a possible causal chain was discussed. It started with economic recession, changes in food distribution and little access to complementary sources of food. This led to a monotonous carbohydrate diet and an unbalanced nutritional state, where tobacco and other toxins may have interacted with the metabolic disorder to induce neuronal damage. The disease distribution found was difficult to explain as the isolated effect of a toxin or infectious agent. The conceptual outline of the toxic-nutritional hypothesis was also expounded, using the works of Dr. Madam as historical background. The disease was considered an optic-peripheral neuropathy, that could be associated to dorsal lateral myelopathy. Starting from the known causes of optic and peripheral neuropathies, other causes of genetic origin were ruled out, as well as those due to systemic metabolic diseases, since they are not epidemic. Acquired causes of epidemic behavior were proposed, such as: toxics, deficiencies, association of both (toxic-nutritional) and infections. In this sense, the etiopathogenic hypothesis proposed that the altered nutritional state adversely affected the detoxification mechanisms and the antioxidizing systems. Together with the aforementioned exposure to toxic substances from smoking, which contributes to depressing defense mechanisms, this may have triggered metabolic stress at the cellular level, disturbing the energy-producing mechanisms required to maintain adequate functioning of the nerve fibers. Considering the results obtained in the multiple studies carried out, two pathogenic mechanisms may be responsible for the neuronal damage characterizing this disease: oxidative stress, because of a lack of antioxidants and a disturbance of the antioxidizing systems, and the exposure to toxic substances from smoking that causes an increased depression of the cyanide detoxifying mechanisms. To sum up, the neuropathy epidemic in Cuba cannot be attributed exclusively to the damage caused by depressed nutritional state. However, this state created the conditions necessary for the development of the aforementioned mechanisms. Thus, we can define it as a toxic-nutritional neuropathy. Toxic-Nutritional Neuropathy The joint discussion session exceeded all expectations. Different and controversial ideas were exchanged, which, at times, were compared to the Italy-Brazil World Championship soccer match. The essential discussion dealt with the primary hypotheses about the cause of the disease: toxic-nutritional and viral. According to some, the methodology for demonstrating the presence of viruses was correct: the virus may be latent and act as a cofactor, together with the nutritional or toxic factors. Another aspect discussed was patient follow-up, which will clear up some unknown facts. In this regard, continued collaboration would be helpful. The National Follow-up Program for epidemic neuropathy patients includes three main elements:
Despite follow-up and the best therapeutic protocols, some patients do not recover. Patients maintaining a static course is presented. It is necessary to analyze the causes contributing to this. The participation of the Cuban President, who took interest in the results of other treatments including spa treatment, the role of vitamin therapy in disease control, the behavior of new cases and whether they were taking vitamins prophylactically, led to new explanations on this subject. The Cuban President pointed out how much has been achieved since the beginning of the epidemic and the need to continue looking closely into the causal factors, as well as follow-up and control of the patients. The role of the family doctor was analyzed--in follow-up, control and prevention of cases, as a researcher into the epidemic’s causes and as a care provider for the patients. About spa therapy, some data demonstrated positive results in patients treated at the San Diego de los Baños spa in Pinar del Río province. A therapeutic protocol including vitamins, methionine and sulfur baths was used. The application of rehabilitation protocols for the most severe cases was recommended here, as it was in the Elguea spa in Santiago de Cuba province. Collaboration projects with international organizations were detailed and rehabilitation was emphasized. Final Considerations This meeting efficiently summarized studies of this disease to date by specialists from prestigious national and international institutions. The results obtained will enrich knowledge about the different aspects related to it, as well as enable their application to the integral development of science. The objectives of the workshop were achieved and expectations exceeded. Nevertheless, pursuing investigations and designing other research that responds to present needs was recommended. A more integral character in the multidisciplinary and multi-centered approach with which these studies have been carried out was also recommended. These four days of work have signaled the climax of a prolonged, intense and fruitful stage of scientific and medical cooperation. At the same time, the workshop defined new joint tasks to be developed in the future, both as regards organization, medical care and research. This text was originally published in Neuropatía epidémica en Cuba, 1992-1994. Rojas Ochoa, F. ed., La Habana, Editorial de Ciencias Médicas, 1995: 219-227. |
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