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ABSTRACT Retroviruses are common in the African continent. The roles of HIV-1 & 2 HTLV – I in the pathogenesis of disorders of the nervous system in Africa have not been well elucidated. To evaluate the individual roles and the interplay of these retroviruses in the pathogenesis of the nervous system morbidity, we studied 1872 patients admitted with neurological disorders in the national hospitals in 6 African countries in a period of 4 years. Keywords: HTLV-1, HIV, neurology, Africa RESUME Les rétrovirus sont fréquents sur le continent africain. Les rôles du VIH-I et de HTLV-1 dans la pathogénèse des troubles du système nerveux en Afrique n’ont pas été clairement élucidés. Pour évaluer leur role et les interrelations existantes entre ces retrovirus dans cette pathogénèse, nous avons étudié 1872 patients atteints d’affection neurologique hospitalisés dans les hopitaux nationaux de six pays africains sur une période de quatre ans. Mots clés : Afrique, HTLV1, HIV INTRODUCTION The Human Adult T Cell Leukemia Virus type-1 (HTLV-1 ) has been definitely associated with two diseases: adult T cell leukemia/lymphoma (ATL) and the HTLV – 1 associated myelopathy/Tropical spastic-paraparesis(HAM/TSP), although most infected persons are asymptomatic. The syndrome of HAM/TSP has been reported in both HTLV -1 endemic and non-endemic zones throughout the world with an estimated lifetime risk of 0.25% in persons infected with HTLV – I (Aboulafia 1995). As these viruses have similar routes of transmission (Preux et al. 1995, Suzuki and: Gojobori, 1998), it is that patients infected with HTLV – I will be coinfected with HIV -I, or 2. These viruses can be transmitted in utero and by transfusion of contaminated blood and cellular products, sharing of needles among the intravenous drug users, sexual intercourse and breastfeeding. In many parts of Africa, the use of unsterile or inadequately sterilized – needles and other surgical equipment in under equipped medical centers, and by traditional medicinemen, are important means of viral transmission that are particularly confined to this part of the world. The role of coinfections is not clear: HTLV- I may accelerate the progression of HIV but whether the emergence and the spread of HIVs has had any effect on HTLV – I is still debated (Preux et al. 1995). Beilke et al. (1998) suggested that the presence of one virus may activate the emergence of clinical disorders in the other probably due to up-regulation of the coinfecting retrovirus. In HTLV – I infection, histopathological studies of the spinal cord have demonstrated demyelination lesions; a chronic inflammatory reaction with mononuclear cells and perivascular cuffing. This means that HTLV-1 may not only be lymphotrophic but also neurotrophic (Aboulafia 1995). Due to the long latency between the viral infection and the development of disease, the implication of this virus in the pathogenesis of neurological disorders in Africa may be very important considering its relatively elevated endemicity in some parts of this continent (de The et al. 1989 and Verdier et al. 1994). Recently, for instance Bartholomew and collegues (1997) suggested a possible causal association between this virus and lower motor neuron facial nerve palsy, mainly among the people of African descent, living in Tobago and Trinidad. In Africa, the range of HTLV – I associated neurological syndromes remains to be determined. To determine the roles ofHTLV-l, HIV – 1 and 2 and their coinfections in the etiology of the nervous system morbidity in Africans, we studied 1872 neurological patients admitted in the neurology and general medical wards in six African countries between 1987 and 1991. The initial phase of this work was published by Ramiandrisoa et al. (1991). PATIENTS AND METHODS Clinical Analysis Between March 1987 and July 1991, all patients with neurological disorders admitted to neurology wards or general medical wards in University Hospitals of Brazzaville, Lome, Dakar, Abidjan, Ouagadougou, and Conakry were evaluated. These hospitals are found in the administrative capitals of Congo, Togo, Senegal, Ivory Coast, Burkina Faso and Guinea respectively. The neurological diagnoses were established by the responsible neurologist in each of these centers. In total, 1872 patients were included in this series. The sex ratio was 1.8 with 1214 (64.9%) males and 658 (35.1%) females. The mean age was 43.9 ±17.5 years. After the clinical and paraclinical data (total blood count with and white cells differential count, urea and electrolytes analysis, cervical-spine and/or thoraco-lumbar X-rays, CSF studies and myelography when indicated) were analysed, patients were grouped in six clinically homogeneous disease groups . Those with spatic paraparesis of unknown aetiology having an insidious onset, slowly and chronically progressive, without remission or acute on chronic episodes, frequently associated with paraesthesiae and hypoesthesiae of the lower limbs, lumbago and sphincter dysfunctions were classified as tropical spastic paraplegia or paraparesis (TSP). Peripheral neuropathies from diverse causes including vitamin deficiencies, chronic alcoholism and dietary toxicities were identified. These mainly presented as tropical ataxias (the principal presentation of tropical myeloneuropathies). Isolated cranial nerve palsies were notably represented by facial palsy of lower motor neuron type and the oculo-motor nerve palsy. Meningo-encephalitis was diagnosed on clinical and CSF study and classified appropriately. All medullary disorders of diverse causes such amyotrophic lateral sclerosis, idiopathic myelopathies other that TSP were classified as myelopathies. Strokes, parkinsonism, Parkinson’s disease, dementias, epilepsies, and other diseases were classified together. Laboratory analysis Ten milliliters of venous blood were drawn from each patient and immediately centrifuged. The sera were then deep-frozen to negative 20°C and airlifted to France in dry-ice isothermal containers. The cold chain was maintained as such, and the samples were analysed in the Department of Bacteriology and Virology in the Faculty of Medicine in Limoges University. Screening for HTLV-l Screening for HIV Statistical Analysis The Mantel-Haenzel chi(2) method was used for group comparisons. Fisher’s exact-test was applied when the theoretical size was below 5. Given the high numbers of comparisons to be done, the threshold of significance was maintained at 1%o. RESULTS Myelopathies form the most frequently observed disorder (n=425) in this hospital based study, among which 107 had TSP. Peripheral neuropathies are the second commonest presenting disorder (n=254). These were mainly due to chronic alcoholism and dietary toxicities. Isolated cranial nerve palsies were less frequently encountered (n=74) probably because people will tend not to consult for this seemingly minor health problem infront of other serious medical and economic difficulties that engulf majority of people living in these countries. Table 1 and Table 2 illustrated the retroviral seroprevalences; 246 (13.1%) wee seropositive for at least one of the viruses. There was a high co-infection rate as 23.6% seropositive patients had multiple infections. HIV-1 was significantly responsible for the majority of the neuromorbidity. Patients mainly presented with meningoencephalitis with 27.7% being seropositive. 13% of those with cranial nerve palsies were seropositive for HIV-1, while a non significant 1.9% of patients with TSP was HIV – I positive. A marginal, statistically nonsignificant group of patients with myelopathies were HIV-2 positive (1.6%). Only 0.3% were indeterminate for HTLV-1. These were treated as negative in subsequent analysis. HTLV-1 alone, or in association with HIV-1, or HIV 2, was found in 20 (18.7%) patients with TSP. This was significantly high when compared to the other clinical categories (p < 0.00l). In 28% of the cases infected by HIV-1, another retrovirus was present. This was the case in 64% of HIV - 2 positive patients and 43% of HTLV-1 positive patients. The co-infection.rates differed significantly (p<0.0001) among the three retroviruses. DISCUSSION Retroviruses so called because of their genome which is composed ofRNA were among the first viruses to infect mammals. Their implication in human disease was not known untill early 80s when HTLV – I was identified by Poiesz and coworkers (1980) from a patient with cutaneous T cell lymphoma. Since then, the development of sero-epidemiological and molecular studies has provided great insight into the biology and transmissibility of these viruses. Though the present study was not random, it was quite exhaustive as it covered a large zone of.the Sub-Saharan Africa endemic for these retrovirusesand involved a large number of patients. Moreover strict clinical and laboratory criteria applied minimised the possible inclusion biases. WHO criteria (September 1990) for positivity by Western Blot method was used. As from 1991 the new method targeting the recombinant envelop proteins has allowed the possibility to differentiate between the formally cross reacting HTLV -1 & 11. It is admitted that some samples which were actually HTLV – 11 positive could have been classed as indeterminate using the older method. We excluded all indeterminate samples in the final analysis, and therefore HTLV – Tl effect would not affect the final results. Apart from a few clusters found among the Congolese Bambuti Efe Pygmies (Vandamme, 1998), the occurrence of HTLV – II is very low in Africa (Bonis et al. 1994) and this virus has not been etiologically linked with any disease although an increasing number of case reports suggests its possible associations with several clinical conditions (see Abiad and Hershaw, 1997) Several workers have in the past demonstrated a significant association between HTLV- I andTSP though the discordance rate has been quite high among authors. In Martinique, Gessain et al (1985) described for the first time the association between HTLV – I and TSP. In their series, 59% of people with TSP were seropositive for HTLV – 1. In high endemicity zones for HTLV -4, the endemicity for TSP was also high. In a separate study, in Martinique, Vernant and his colleagues (1987)found78%positivityforHTLV-l inTSP patients. Roman and co-workers (1987) in Seychelles, found 85% of the patients seropositive for HTLV – I presented with TSP. In Jamaica Rodger-Johnson and co-workers (1988) found 67%. In Africa the relationship HTLV – I /TSP is much less evident than in other regions with high endemicity for this virus. Only 18.7% ofthe patients with TSP in this study were seropositive for HTLV – 1. Delaporte et al. (1989) had found only between 3 and 7% of TSP patients to be seropositive for HTLV -I in the humid tropical forest in Gabon. None ofthe TSP patients investigated by de The .and co-workers (1989) in Ivory Coast and Zaire were seropositive. Hugon and colleagues (1990) reported only some sporadic cases. The reasons for this discrepancy between Africa and other regions are not clear but it may be that the HTLV – I is not be playing an important role in the causation of TSP in the Africans. Errors arising from the sampling and analytical techniques, false negativity of the screening methods (notably in some subjects seropositive by PCR), the long latency going to several years be- tween infection and first clinical symptoms, the short life expectancy among the Africans are some of the factors that could explain these discrepancies. However, other unidentified factors like toxic substances, nutritional disorders, genetic susceptibility, climatic and geographical conditions, infections or co-infections with bacteria or other viruses or even parasitic infestations could be responsible for the pathogenesis of TSP/HAM rather that HTLV-1 (Montgomery, 1993). Though HTLV-1 has been implicated in other disorders like polyradiculoneuropathies and polymyositis (Vernant et al, 1991) its exact role in the pathogenesis of these illnesses has not been clearly demonstrated. We did not find in this study any demonstrable relationship between HTLV-1 and other neurological disorders. The other retroviruses on the other hand seem to play a relatively bigger role in pathogenesis of disorders of the nervous system. HIV is responsible for peripheral neuropathies, myelopathies and meningoencephaUtis. We found a significant association between HIV-1 and meningoencephalitis. HIV – 2 did not seem to be of any significant contributory value. The interplay of HTLV-1 virus in the disease pathogenesis in the HiV epidemic remains unclear. While there are several reports of pathogenic potentialization by this virus in HIV infection, viable evidence is lacking. The role of the interplay of these viruses in the pathogenesis of neurological disorders in the African continent, where there is a major coexistence of these viruses, is a subject of major interest, particularly because of their neurotropism. Superinfection withHIVs may accelerate the occurrence of clinical symptomatology of paraplegia in HTLV – I infected patients probably secondary to.an immunological reaction (Preux et al. 1995). Our study found a high coinfection rate in a small group of patients, and even where coinfection was found, higher chances of developing a neurological complication in patients was not evident. Other independent cofactors are probably responsible for the clinical evolution in patients infected with these retroviruses and need to be investigated.
Table 1: Patients distribution against towns in different countries.
Table 2: Seroprevalence by clinical categories against the retroviruses.
SUMMARY Recent studies have suggested a possible relationship between onchocerciasis and epileptic seizures. In 1996, we identified 344 epileptics in the North Western region of Central African Republic in the Ngaoundaye sub-prefecture (44100 persons). The prevalence of epilepsy was therefore 10.9%o. This prevalence varied positively with the onchocerciasis association between onchocerciasis and epilepsy. However this survey was subjected to biases and other studies are needed to confirm this results. Keywords: Africa, Central African Republic, Epilepsy, Onchocerciasis RESUME Des études recentes ont suggére une relation possible entre l’onchocercose et la survenue de crises épileptiques. En 1996, 344 épileptiques ont été identifiés dans la région Nord-Ouest de la République Centrafricaine, dans la sous-préfecture de Ngaoundaye (44.l00 personnes). La prévalence de l’épilepsie etait par conséquent de 0,9%o habitants. Cette prévalence variait positivement avec le niveau d’endémicite onchocerquienne dans les villages (r=0,73 ; p<0,001). Ces résultats descriptifs sont en favour d'une association entre l'onchocercose et l'épilepsie. Toutefois cette étude était sujette à des biais et d'autres études sont nécessaires afin de confirmer ces resultats. Mots clés : Afrique, Onchocercose, Epilepsie, République Centraficaine INTRODUCTION Recent studies done in Uganda(1) and Burundi (2), have suggested a possible relationship between onchocerciasis, a dermal cutaneous filariasis causing river blindness, and epileptic seizures. However, this relationship was not found in a study done by our team in Burkina-Faso3 in an onchocerciasis hypoendemic region. Certain authors indicated the need for further investigations4, ln l996,a census carried out by health agents in 40 villages in the Ngaoundaye sub-prefecture of 44 100 persons, in the North Western region endemic for onchocerciasis of Central African Republic, identified as well, people with epilepsy in the region. A positive correlation between the onchocercal endemicity and the prevalence of epilepsy (r=0.73; p<0.001) and a negative correlation between epilepsy prevalence and the mean distance of the villages from the nearest river (r=-0.34; p<0.03) were evident. These descriptive results are in favour of an association between onchocerciasis and epilepsy. This study has certain biases: the number of epilepsy cases was probably underestimated, however, this underestimation was uniform among areas of different onchocerciasis endemicities; distances were estimated but not accurate measurements; endemicities were assessed using a rapid method on a community basis and not on individuals; the analytical method was cross-sectional which does not eliminate other confounding factors. Despite all these limitations, these results seem particularly interesting and indicate to set up a detailed study in this country, with epilepsy being confirmed by a neurologist and onchocerciasis confirmed by skin biopsies. Table: Prevalence of epilepsy and mean distance from the nearest river according to onchocerciasis endemicity. Central African Republic, 1996
Onchocerciasis endemicity THE VALIDITY OF FILTER PAPER BLOOD SAMPLING FOR THE DETECTION OF HTLV-I SEROPOSITIVITY: A BENIN STUDYABSTRACT Screening for HTLV-I requires a venous blood sampling, which can be difficult during large scale epidemiologic surveys. The aim of this study was to assess the ability to detect antibodies to HTLV- 1 from blood collected on filter paper. This study was conducted in Benin and comprised of 109 subjects. The sensitivity of the method was 81%. The specificity was 100%. Concordance between serologic testing for HTLV-I by venipuncture as compared with collection on filter paper was poor. Other kits must be tested to evaluate if structural or functional differences diagnostic kits may explain this lack of sensitivity. Keywords: Africa, Benin, HTLV-l,Filter paper, Benin, Africa, epidemiology, Evaluation RESUME Le depistage d’HTLV-l requiert un prélèvement de sang veineux, ce qui pent être difficile dans le déroulement d’études épidémiologiques a large échelle. Le but de cette étude était d’évaluer.la possibilité de détecter des anticorps centré HTLV-1 sur du sang collecté sur papier filtre. Cette etude a été conduite au Bénin et incluait 109 sujets. La sensibilité de la méthode était de 81%. Sa spécificité était de 100%. La concordance entre les sérologies réalisées sur du sang veineux et celles réalisées sur papier filtre était mauvaise. D’autres kits devaient être testeés afin d’évaluer si des differences structurelles ou fonctionnelles entre ces kits de dépistage peuvent expliquer ce .manque de sensibilité. Mots clés : Afrique, Benin, HTLV1, Evaluation, Epidémiologie, Papier filtre INTRODUCTION Screening for HTLV-I requires a venous blood sampling, which can have certain drawbacks during large-scale epidemiologic surveys. Our aim was to assess the ability to detect antibodies to HTLV-I from blood collected on filter paper, a more convenient method that is already in use and has been validated in screening for the human immunodeficieney virus (HIV) [1]. A previous study was conducted by our team in Burundi and showed that the agreement between the two sampling methods to detect the seropositivity for HTLV-I was poor [2]. In order to assess this method on a higher number of patients, the present study was conducted in Benin in March 1995 where a cohort of HTLV-I positive subjects is surveyed since 1991 [3]. The study group was comprised of 109 subjects. Paired specimens were obtained: 10 ml of blood by venipuncture, and capillary blood obtained by lancet finger puncture which provided three blood spots, each I cm indiameter on chromatography paper (Whatman 311, Polylabo). The filter paper was let to dry in ambient air and then kept in a refrigerator at 40 Celsius in an air-tight container with desiccant. The biological analysis were performed within three weeks in Limoges (France) in the same laboratory without patient identification. Serologic testing for HTLV-I was performed using the same diagnostic kits for the serum and filter paper (screening with ELISA technique-HTLV-1/11, Abbott Laboratories, Chicago, USA-and confirmation of the samples considered positive using a Western Blot assay – Bioptim 2.3, Diagnostic Biotechnology, Singapore-). A 5mm diammeter punch from a filter paper spot of capillary blood was obtained and eluted in 200 microliters of the diluent supplied with the kit over a 12 hours period preceding the serologic testing. The tests were performed on the eluate thus obtained. Criteria for HTLV-I seropositivity were lhe recognition of two different proteins: gag (pl9 and/or p24) and env (gp46 and/or rgp21) [4]. The sensitivity of the method was 81% (Table 1). The specificity was 100%. HTLV-I: Human T cell Leukemia Virus type 1; WB: Western Blot; ELISA: Enzyme Linked ImmunoSorbentAssay. Concordance between serologic testing for HTLV-1 by venipuncture as compared with collection on filter paper was poor. The latter technique has the disadvantage of global decrease in sensitivity. These results do not confirm those by Jeannel et al. [5] who found complete concordance between the two serologic testing methods for HTLV during a study conducted in Zaire in 122 subjects. However, details on the sampling method used by these authors and the number of seropositive subjects in their study were not given. Compared to our previous study in Burundi [2] carried out with a smaller sample of positive subjects, the sensitivity of filter paper has increased from 66.7% to 81.0%. Difference in the methods of conversation of the samples could explain this improvement (shorter delay to perform biological analysis; filter papers kept in a refrigerator). However, this sensitivity is still too low for screening purposes. To evaluate if structural or functional differences between diagnostic kits may explain this lack of sensitivity, other kits must be tested. It may be also be useful to assess antibodies stability under various conditions, particularly climatic. Table 1: Serologic testing for HTLV-I using filter paper and serum after confirmation by WB in subjects that tested positive by ELISA in 109 subjects, Benin. March 1995.
RESUME Les auteurs rapportent les cas cliniques de 12 patients mauritaniens atteints d’une pathologie hérédodégénérative du système nerveux. Ces 12 patients se répartissent en deux groupes: un premier groupe de 9 patients pour lequel un caractère familiar est retrouvé et un deuxieme groupe ou l’affection semble présenter un caractère sporadique. Les affections neurologiques du premier groupe sont lamaladie de Friedreich et l’atrophie olivo-ponto-cérébelleuse; dans le deuxieme groupe, l’hérédo-ataxie de Pierre-Marie, la maladie de Ramsay-Hunt et la maladie de Friedreich. Les partictilarités cliniques sont relevées. Les auteurs attirent l’attention sur cette pathologie hérédodegenerative mal connue en Mauritanie. Mots clés : Afrique, neuropathies hérédo-dégénératives, Mauritanie SUMMARY The authors report 12 clinical cases of Mauritanian patients suffering from heredodegenerative diseases of the nervous system. These patients could be separated in two groups: the first group of nine patients for whom a family history of heredo-de-generative disorders was found and a second group where the diseases seemed sporadic. The disorders in the first group were Friedreich disease, olivo-ponto-cerebellar atrophy and in the second group an heredo-ataxia (Pierre-Marie disease), a Ramsay-Hunt disease and a Friedreich disease. The clinical charateristics are noted. For the first time, the authors underline the presence ofheredo-degenerative disorders in Mauritania. Keywords: Africa, Heredo-degenerative diseases, nervous system, Mauritania INTRODUCTION Le service de Neurologie du Centre Neuro-Psychiatrique (CNP) de Nouakchott a été crée en 1991 avec une capacité d’hospitalisation de 20 lits, une division de kinésithérapie et une division d’electrophysiologie (EEG, EMG). La moyenne annuelle des consultants est de 2.500 malades et 250 patients sont admis en hospitalisation par an. Malgré la prédominance de A.V.C, des épilepsies et de la pathologie périphérique, on rencontre comme partout ailleurs des pathologies rares parmi lesquelles les hérédodegenerescences du système nerveux central (S.N.C). Cette pathologie de plus en plus étudiee grâce à la génétique moléculaire demeure un problème médico-social réel du fait de ses conséquences physiques. Cette étude qui porte sur 12 patients, a pour but de rapporter les aspects cliniques de cette pathologie mal connue en Mauritanie. PATIENTS ET METHODES Méthodologie Notre étude représente une série prospective de 12 cas de pathologie hérédodégénérative du S.N.C colligés de Mai à Decembre 1997 dans le Service de Neurologie du Centre Neuro-Psychiatrique de Nouakchott en Mauritanie. Notre travail s’appuie sur l’étude clinique des patients: neurologique, ophtalmologique et cardiaque. Les explorations complémentaires (scanner cerebral, électromyogramme) ont ete réalisees chez certains patients. Patients Les 12 patients se repartissent en deux groupes:
-un deuxieme groupe ou l’affection semble présenter un caractère sporadique et qui est composé de 3 patients agés de 10 ans, 20 ans et 49 ans. Dans les antécédents familiaux de ce groupe, seul un patient suspect de maladie de Friedreich a des parents qui sont cousins au 3e degre . RESULTATS Les différentes manifestations cliniques des patients sont décrites ci-dessous: 1. une premiere serie familiale de l’ethnie maure noire ou 4 enfants, tous de sexe masculin, sont atteints de la maladie de Friedreich; – leur âge est de 18 ans, 16 ans, 12 ans et 3 ans; – le motif de consultation est d’ordre social les parents de ces enfants désirant une aide des pouvoirs pour leur prise en charge médico-sociale et scolaire; – le début des troubles se situerait à l’age de 3 à 4 ans pour l’ainé, à l’age de 3 ans pour le second et le quatrieme et à l’âge de 4 ans pour le troisième frère. Les symptomes cliniques étaient faits de tremblements du chef, d’un retard de la marche et d’une instabilité du regard. Au fil des années, il s’installa un tremblement d’action et d’attitude, une dysarthrie et une difficulté accrue à la marche. L’ainé de ces 4 enfants est grabataire au moment de l’examen. Le cadet de cette fratrie présente un début de signes semblables: tremblement du chef, retard a la marche et instabilite du regard. Leurs parents sont vivants et bien portants sans lien de consanguinité. Dans la fratrie, il existe une fille ainée qui ne présente aucun élement significatif de cette maladie. A l’examen neurologique, on note un syndrome cérébelleux cinetique et statique aux différentes épreuves: adiadococinesie, hypermétrie, instabilité à la marche. Une dysarthrie est presente chez les 3 patients plus âges avec une voie explosive. Un syndrome pyramidal est quasi-constant avec des réflexes ostéo-tendineux vifs, diffusés, polycinétiques avec trépidation épileptoide et clonus de la rotule et un signe de Babinski bilateral. Les second et troisieme frères ont une démarche ataxique avec fauchage. L’examen general montre unsyndrome dysmorphiqueavec des pieds creux chez les 3 frères les plus âges. L’examen ophtalmologique est normal chez les 4 patients en dehors d’un nystagmus d’installation precoce. L’examen cardiologique ne montre pas d’anomalie clinique. L’association d’un syndrome cérébelleux statique et cinetique, d’un syndrome pyramidal d’aggravation progressive et d’un syndrome dysmorphique fait évoquer le diagnostic d’heredodenerescence, imposant des explorations complementaires: – Electromyogramme montrant une atteinte axonomyélinique proximale chez les 3 patients plus ages. 2. Une deuxieme série familiale d’ethnie maure blanche composée de 4 patients, un de sexe feminin âgé de 29 ans et trois de sexe masculin, âgés de 27, 22et 18 ans. Le motif deconsultation est lie a une inquietude des parents devant des troubles divers d’aggravation progressive: tremblements, troubles de la deglutition. – Le debut des troubles se situerait a l’adolescence avec des ages differents: 17 ans pour l’aine, 15 ans pour le second, 18 ans pour le troisieme et 11 ans pour le 4e frère. Les symptomes de début étaient des tremblements des le moindre mouvement avec installation progressive d’une dysarthrie chez le 3e et le 4e frere, des troubles de la déglutition chez les 2e et 4e et des troubles de la marche aggravés par le syndrome cérébelleux chez l’ainee. – Leur père est vivant et bien portant et la mère est décédée alors qu’elle semblait etre atteinte d’un syndrome cérébelleux et des troubles de la déglutition. Chez ces parents il existe une consanguinité vers la 7e génération. Cette famille a 6 enfants dont une fille et un garcon qui ne présentent aucun symptome particulier. – L’examen neurologique montre un syndrome cérébélleux cinetique et statique chez tous les patients avec un tremblement d’action et une dyssynergie. Ce syndrome cérébelleux est plus accentué chez l’ainée entreinant un trouble de la marche. La dysarthrie est cérébelleuse avec une voie scandée et explosive; cette dysarthrie cérébelleuse est retrouvée chez deux patients (3e et 4e freres). II existe de plus un trouble de la L’examen général ne montre aucun syndrome dysmorphique. L’examen ophtalmologique revèle une ophtalmoplegie supranucléaire. L’examen cardio-vasculaire est normal. Devant ces différents syndromes (syndrome cérébelleux cinetique et statique, une ophtalmoplegie et des troubles inconstants de la déglutition), des explorations complémentaires ont ete realisees: – Electrocardioographie et echographie cardiaques normales chez les 4 patients.
-Tomodensitometrie cérébrale réalisee chez 1’ainée montrant une atrophie pontique et chez le deuxieme patient une atrophie cérébelleuse. Le diagnostic d’atrophie olivo-ponto-cérébelleuse est retenu dans cette famille. 3. Une patiente, fille unique âgée de 18 and, d’ethnie soninke est née de parents cousins au premier degré. Son père vivant est bien portant et sa mère est décédée d’une affection s’exprimant par une ataxie à la marche aggravée par la grossesse, des troubles du langage et de la deglutition. Son décès etait survenu apres un accouchement. Le début des troubles chez cette patiente serait survenu à l’âge de 18 ans, marqué par une instabilite à la marche et des tremblements. Progressivement, ces symptomes s’aggravèrent avec au moment de l’examen une grande difficulté à se tenir debout et à marcher. L’examen neurologique met en évidence un syndrome cérébelleux statique et cinetique très marqué. L’exploration ophtalmologique est normale. L’exploration scanographique cébrale montre une atrophie cérébelleuse. Cette symptomatologie fait évoquer le diagnostic d’atrophie olivo-ponto-cérébelleuse. 4. Une série de 3 patients dans laquelle la survenue des différentes symptomatologies est sporadique. Patient 1 Un premier patient de 50 ans, maure blanc, de sexe masculin, cadre supérieur, ne présente pas d’antécédents pathologiques notables en dehors d’une notion de dysarthrie de survenue tardive chez la mère et un oncle maternel. II n’existe pas de consanguinité des parents. Le début de sa maladie remonterait à 1969 à l’age de 20 ans avec apparition lentement progressive de troubles de l’équilibre et de la marche. II s’installa quelques années plus tard des troubles de la coordination aux membres supérieurs et des troubles de la parole. Ces troubles ont occasionneé de nombreuses consultations chez divers medicins et devant la normalité du bilan biologique et radiologique, le diagnostic d’une affection hérédodegénérative du systeme nerveux était evoque. Depuis trois ans, le patient rapporte une aggravation de troubles de la parole surtout en fin de joumée, des difficultés d’écriture et de déplacement sans aide. L’examen neurologique montre une importante ataxie à la marche, un syndrome tétrapyramidal et un syndrome cérébelleux stato-cinétique. II n’existe par ailleurs ni trouble sensitif ni trouble de la déglutition. Le réflexe photmoteur est present Le voile est mobile et le réflexe nauséeux est présent. L’examen ophtairnologique met en évidence une ophtalmoplégie supranucléaire. Les examens biologiques réalises à Rabat au Maroc out montré un bilan lipidique normal; un taux de vitamine B12 a la limite inférieure de la normale; une électrophorese des protides sériquesvnormale; un bilan thyroidien normal; une glycémie à jeun et post-prandiale normale; une numération formule sanguine, une vitesse de sédimentation, un ionogramme sanguin et un bilan hépatique normaux: le dosage de la vitamine E à la limite inférieure de la normale; des dosages de apolipoproteines A et B normaux; un cuivre sérique et urinaire normal; une céruleoplasmine normale. Patient 2 Un deuxieme patient âgé de 19 ans, d’ethnie maure noire et de sexe masculin, est vu en consultation de Neurologie pour la premiere fois en 1995 pour tremblement. Ce patient a présenté des crises convulsives depuis 1986 avec mise en route de traitement ambulatoire anticomitial sans grande efficacité. C’est l’aggravation des tremblements de facon progressive associée a une agressivite vis a vis de sa mère qui amène les parents a presenter ce patient en consultation de facon plus reguliere. Aucune consanguinite n’est retrouvée chez les parents qui sont vivants et bien portants. L’examen neurologique montre unquotient intellectuel bas, un syndrome cérébelleux cinetique avec dysmetrie, adiadococinesie et dvsarthrie cérébelleuse. L’examen général est strictement normal. L’électroencéphalographie montre des anomalies irritatives survenant parfois par bouffées bilaérales pseudopériodiques. L’exploration tomodensitométrique encéphalique est normale. Devant cette triade constituée d’une épilepsie, d’un syndrome cérébelleux et d’une démence, une maladiede Ramsay’ Hunt est évoquee. Lévolution de la comitialité est bonne sous carbamazépine et clonazépam. Patient3 Un troisieme patient, né en 1988, de l’ethnie maure blanche, est venu en consultation de neurologie pour troubles de la marche atype d’instabilité. Le debut en fait se situerait a l’âge de 5 ans et l’évolution a été progressive. Dans les antécédents, il existe une consanguinité au 3e degre entre les parents. Ce patient a deux soeurs indemnes de toute maladie. L’examen neurologique montre un syndrome cérébelleux statique et cinétique, une ataxie mixte cérébelleuse et sensitive, des réflexes ostéo-tendineux abolis aux 4 membres, un signe de Babinski bilatéral. L’examen géneral montre un syndrome dysmorphique avec des pieds creux et une scoliose verteébrale. II s’agit probablement d’une maladie de Friedreich. DISCUSSION L’existence d’un syndrome cérébelleux statique et cinétique d’évolution chronique et lentement progressifchez laplupart de nos patients est très evocatrice d’une dégénérescence du S.N.C. Les donnees de la litterature concernant la pathologie hérédodégénérative sont nombreuses et les études portent actuellement sur les aspects genetiques. Cette première étude réalisée en Mauritanie porte sur les données cliniques. Chez les patients qui presentent des signes evocateurs de maladie de Friedreich, plusieurs – L’age de survenue précoce (entre 3 et 4 ans) de la maladie chez les 5 patients differe de ce qui est classiquement decrit. En effet, cet age de début se situe habituellement autour de l’adolescence notamment vers 10-12 ans(2). – Les signes dysmorphiques à type de pieds creux ne sont retrouves chez tous les patients presentant cette affection, alors que la scoliose n’est retrouvée que chez le patient presentant le caractère sporadique. -Les signes cliniques sont dominés par ie syndrome cérébelleux et le syndrome pyramidal qui alterent considérablement la marche. L’électromyographie faite chez 2 patients de cette famille retrouve une atteinte axonomyelinique avec atteinte proximale. Cet aspect pathologique de l’électromyographie de stimulation est frequemment rencontre dans la maladie de Friedreich. La maladie de Freidreich fait partie des ataxie autosomiques récessives précoces et n’a pas, dans cette étude un caractère génétique défini. En effet, dans les 2 types de cette affection (type I lie au chromosome 9 et type II avec déficit isolé en vitamine E lié au chromosome 8), le tableau clinique est globalement similaire en dehors de quelques particularités comme le tremblement du chef retrouvé chez 4 malades. Les dosages biochimiques plus approfondis (vitaminiques notamment), et l’étude chromosomique ne peuvent être réalises actuellement à Nouakchott. L’age de début des symptomes du patient atteint d’une de Pierre-Marie se situe a 29 ans. L’evolution lentement progressive a abouti actuellement a la dépendance du sujet vis a vis de son entourage pour toutes ses activités de la vie quotidienne. L’existence d’un syndrome tétrapyramidal et d’une ophtalmoplégie les supranucléaire est de description classique. Les explorations complèmentaires ont ete plus poussées chez ce patient ou l’on retrouve: II a été possible de détecter une discrète fuite mitrale sur un ventricule gauche hyperkinetique, associee à une hypertrophie ventriculaire gauche. L’hérédo-ataxie de Pierre-Marie fait partie des ataxies autosomiques récessives précoces. Même si les ataxies héréditaires représentent un groupe hétérogène difficilement classable, l’étude génotypique semble mieux conforme à une classification acceptable que les études anatopathologiques et phénotypiques (7). On distingue les ataxies héréditaires (de type autosornal récessif et un type autosomal dominant) et les ataxies no héréditaires de type symptomatique et de type idiopathique (4). Chez les patients considerés comme attemts d’une atrophie-olivo-ponto-cérébelleuse (AOPC), la precocite des signes de debut (8-17 ans) semble différent des données de la littérature ou le début se situe habituellement entre les 3e et qe décennies (2). Les troubles ophtalmologiques rencontres chez les 4 patients de la même famille sont marqués par unedegenerescence retinienne avec myopie. Dans cette fratrie, la soeur présente en plus une atrophie optique. II est classique de retrouver dans cette pathologie une baisse de l’acuité visuelle avec ophtalmoplegie supranlicléaire et atrophie optique. L’absence de signe extrapyramidal de démence et de mouvements anormaux de type choréique et dystonique, rapproche ces patients du type III de l’AOPC où ie support génétique est encore inconnu. Cependant d’autres tableaux cliniques décrits ailleurs avec une démence, des signes cérébelleux et des signes extrapyramidaux ont montré un déficit héréditaire en céruleoplasmine en association avec une hémosidérose (5). La tomodensitométrie cérébrale réalisee chez deux des patients de ce groupe montre une atrophie cérébelleuse. Dans le syndrome de Ramsay-Hunt, la précocite des signes de début est retrouvée classiquement (6). Les crises epileptiques avec un électroencéphalogramme qui montre des bouffées irritatives bilatérales pseudo-périodiques, le syndrome cérébelleux et un profil intellectuel has caractérisent ce syndrome. CONCLUSION La pathologie hérédodegénérative du systeme nerveux central est bruyante par les signes cliniques qu’elle représente et dramatique par ses conséquences sociales. Le développment actuel de la génétique, les progrès de la recherche médicale entrament un regain d’intéret pour cette pathologie. Si l’apport de la tomodensitometrie et de l’imagerie par resonance magnetique est remarquable, car pouvant montrer une atrophie cérébelleuse (3), l’intéret de la tomodensitomérie a également permis dans cette étude, d’éliminer une autre pathologie evolutive notamment tumorale. Quant aux»problèmes socioprofessionnels qui découlerait de ces affections, seule une prise en charge spécifique pent apporter un certain confort chez ces patients souvent grabataires et dépendants. IDIOPATHIC HYPERTROPHIC SPINAL PACHYMENINGITIS OF THE CERVICAL SPINEABSTRACT A case of idiopathic hypertrophic spinal pachymeningits of the cervical spine is discussed (IHSP). IHSP is a rare cause of spinal cord compression due to dural thickening. Magnetic resonance imaging was utilized to make the diagnosis. The patient improved with decompressive surgery. The etiology, diagnosis and treatment (IHSP) is reviewed. Keywords: Pachymeningitis, Spine, Magnetic Resonance Imaging RESUME Un cas de pachyméningite idiopathique médullaire hypertrophique de la moelle epiniere cervicale est rapporté. II s’agit d’une cause rare de compression de la moelle épiniere due a un rétrécissement du fourreau dural. L’imagerie par resonance magnétique a été pratiquée pour faire le diagnostic. Le patient s’est améliore après chirurgie décompressive. L’étiologie, le diagnostic et le traitement de la pachymeningite spinale hypertrophique idiopathique sont revus. Mots clés : Pachyméningite, Rachis, IRM INTRODUCTION Hypertrophic spinal pachymeningitis (HSP) is an uncommon cause of spinal cord compression. Spinal cord compression is due to dural thickening. A number of etiologies have been attributed to its development including infection (tuberculosis, fungi, syphilis); however, in most cases the cause of spinal pachymeningitis is vague or idiopathic. In this report, we describe our experience with this entity and-review the world’s literature regarding this condition. CASE REPORT A 28 year old female presented with weakness of all extremities. She noted the onset of symptoms after a MI, one month prior to presentation at our institution. She hyperextended her neck during the fall. Immediately following the fall she was unable to move due to .paralysis. She gradually improved and was subsequently transferred to our institution. The patient was treated with intravennous steroids prior to transfer. Initial physical examination upon transfer revealed 4/5 strength in all extremities. A patchy hyperesthesia to pinprick was noted diffusely without evidence of a sensory level, the patient was diffusely hyperreflexic with bilateral Babinski signs. Bilateral Hoffmann signs of the upper extremities were present. The patient also exhibited a positive L’hermitte’s sign. The patient was afebrile. Plain radiographs of the cervical spine were normal including flexion-extension views. Magnetic resonance imaging (MRI) of the cranial cervical region was obtained, which demonstrated compression of the spinal cord at CI-C2 due to a dural based process. (See Fig. 1) There was no enhancement of the dura after gadolmium injection. A brain MRI was also performed and was normal. Computerized tomogaphy (CT) obtained after intrathecal contrast injection demonstrated circumferential compression of the spinal cord. (See fig.2) CT with sagittal reconstruction at the cranial cervical junction was normal. (See Fig. 3) Cerebrospinal fluid analysis was normal (WBC – 5mm3, RBC – 10mm3, CSF glucose 64 mg/dl, serum glucose 103 mg/dl), except for an elevated CSF proteins (104 mg/dl). Cerebral spinal fluid cultures were negative for bacteria or parasites. Peripheral white blood cell count and erythrocyte sedimentation rate were normal. Serum testing for syphilis, HIV, plus lupus and rheumatoid factor were normal. Skin testing for tuberculosis (PPD) was normal. The diagnosis of(IHSP) was made based on radiographic studies and the absence of known risk factors for development of pachymeningitis. The patient was taken to surgery where a foramen magnum Cl and C2 posterior decompression was performed. A midline incision in the dura was performed. The dura was found to be thickened (approximately I cm). The thickened dura was partially excised and the specimen was sent for culture and pathology. A dural patch was used to repair the dural defect and to allow for a patulous closure. Fascia lata was used for dural repair. The patient’s postoperative recovery was uneventful. Followup at one year revealed normal strength. The patchy sensory hypestesia had improved. She no longer exhibited a positive L’hermitte’s sign. Pathologic examination of the dura revealed dense collagen bundles with lymphocyte and histiocyte infiltration. There was no evidence of tumor, granuloma, acid fast organisms or fungi. (See fig. 4) Cultures of the excised dura were negative. DISCUSSION Hypertrophic spinal pachymeningitis (HSP) was first described by Joffroy and Charcot in 1869. (6, 17) It is characterized by an inflammatory hypertrophy of the ineninges. We were able to identify 74 cases of idiopathic hypertrophic spinal pachymeningitis in the world’s literature. (2,3,5,8,2,13,16,24,25) Charcot and Joffroy described three stages of the disease. The first stage is characterized by pain (either local or radicular). The second stage is characterized by clinical signs of nerve root compression. The third stage is characterized by spinal cord compression. (6). Pachymeningitis most commonly involves the cervical and thoracic regions. (10). However, it has been described intracranially.(15). In most case, the cause in unknown; however, it has been associated with trauma, metabolic diseases, intrathecal injections (steroids), rheumatoid arthritis, thrombophlebitis. (4,7,11,14,18,20) Infectious etiologies have also been associated with it, including syphilis, tuberculosis and fungi. Tuberclosis and syphilis are the most common identifiable causes of HSP. (1,9,22,23,27) Surgical decompression involving both laminectomy and excision of the dura is advised in most cases since the condition can be progressive. (19,21,26) When patients present with frank clinical evidence of cord compression, the indications for surgery are more compelling. Whether or not the excised dura should be repaired with a graft’ or left open is a subject of debate. Review of the literature shows that success has been achieved with both methods. (6) Kanamori utilized a laminoplasty technique in addition to dural excision. (12) Some cases have been successfully treated with the use of prolonged steroids, immunosupression (cyclophosphamide) and radiation therapy, but the role of these modalities is controversial. (6) Thickening of the dura is the most salient feature on pathologic examination. Dural thickening can range, from 5 to 15 mm. Histologic examination typically reveals a non-specific inflammatory response characterized by dense fibrous tissue with lymphocytic infiltration; however, plasma cells and foreign body giant cells have also been described. (21) When cord compression has been chronic and severe, softening of the spinal cord can occur with formation of the syringomyelia cavities. IHSP does not exhibit a sexual predominance. Cases have been reported in all age groups, except young children. The youngest reported case in 15 and the oldest is 77. (12) Patients can present with both acute spinal cord dysfunction or a more prolonged clinical course taking years to come to a diagnosis. Most patients improve after decompressive surgery; however, continued progression after surgical treatment has been reported. Moreover, some cases have resulted in death either due directly to pachymeningitis or from sequelae of spinal cord compression (e.g. pulmonary embolus). The presence of inflammatory signs (fever, leukocytosis, elevated sedimentation rate) may be associated with a poorer prognosis when compared to cases in which these signs are absent. (12). The diagnosis of HSP should be considered in patients with clinical evidence of cord compression without bony changes on plain radiographs. Both MRI and CT are definitive in making the diagnosis; however, MRI with gadolinium injection is the diagnostic procedure of choice. Decompressive surgery with excision ofthe thickened dura is the treatment of choice in most cases. Articles récents
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