Persistence of tropical ataxic neuropathy in a Nigerian community

OBJECTIVES—The termtropical ataxic neuropathy (TAN) is currently used to describe severalneurological syndromes attributed to toxiconutritional causes. However,TAN was initially proposed to describe a specific neurological syndromeseen predominantly among the Ijebu speaking Yorubas in south westernNigeria. In this study, the prevalence of TAN was determined in Ososa,a semiurban community in south western Nigeria described as endemic forTAN in 1969, and its neurological features were compared withStrachan's syndrome, prisoners of war neuropathy, the epidemicneuropathy in Cuba, and konzo.
METHODS—A census ofOsosa was followed by door to door screening of all subjects aged 10 years and above with a newly designed screening instrument. Subjectswho screened positive had a neurological examination, and the diagnosisof TAN was made if any two or more of bilateral optic atrophy,bilateral neurosensory deafness, sensory gait ataxia, or distalsymmetric sensory polyneuropathy were present.
RESULTS—A total of4583 inhabitants were registered in the census. Of these, 3428 subjectsaged 10 years and above were screened. The diagnosis of TAN was made in206 of 323 subjects who screened positive for TAN. The prevalence ofTAN was 6.0%, 3.9% in males and 7.7% in females. The highest agespecific prevalence was 24% in the 60-69 years age group in women.
CONCLUSION—Theoccurrence of TAN in Ososa continues at a higher prevalence than wasreported 30 years ago. Its neurological features and natural history donot resemble those described for Strachan syndrome, epidemic neuropathyin Cuba, or konzo. The increasing consumption of cassava foods linkedto its causation makes TAN of public health importance in Nigeria, themost populous African country.

     

Controlled trial of hydroxocobalamin and riboflavine in Nigerian ataxic neuropathy

The results are presented of a double-blind therapeutic trial of hydroxocobalamin and riboflavine in Nigerian patients suffering from a degenerative neuropathy. Although no benefit from either vitamin was demonstrated, this may reflect the inadequacy of the dosages used. The results are discussed in relation to the hypothesis that dietary cyanide and cyanogens are responsible, at least in part, for the occurrence of this disease in a malnourished population.     

Biochemical studies in Tanzanian patients with ataxic tropical neuropathy

Data on thiocyanate and vitamin B₁₂ concentrations in plasma from Tanzanian patients with ataxic tropical neuropathy are presented and support the hypothesis that, as in Nigeria, the condition may result from chronic exposure to cyanide or cyanogens from a diet including large amounts of cassava.     

Controlled trial of combinations of hydroxocobalamincystine and riboflavine-cystine, in Nigerian ataxic neuropathy

Chronic cyanide intoxication of dietary origin and riboflavine deficiency are believed to be major aetiological factors in Nigerian tropical ataxic neuropathy. The results are presented of a double-blind controlled therapeutic trial of combinations of large doses of hydroxocobalamin and cystine as cyanide binding agents together with riboflavine or placebos in Nigerian patients suffering from the tropical ataxic neuropathy. No clinical benefit was demonstrable with any of the treatments.     

Sensory conduction study in chronic sensory ataxic neuropathy.

Sensory conduction was studied in six patients with chronic sensory ataxic neuropathy of an idiopathic type and associated with Sjögren's syndrome. Motor nerve conduction velocities were normal in most cases, but sensory nerve potentials could not be evoked in a routine peripheral nerve conduction study. Cortical and cervical somatosensory evoked potentials (SEPs) and evoked potentials from Erb's point were barely recorded by median nerve stimulation at the wrist. When the median nerve was stimulated at more proximal points, clear potentials were recorded from Erb's point, but cortical SEPs were still hardly elicited. Thus the sensory nerves are centrally and peripherally involved in this condition, and the involvement is more prominent in the distal portion in the peripheral nerve. These findings suggest that central-peripheral distal axonopathy is a process involved in this illness and that the dorsal root ganglia may be primarily involved, in accord with previous pathological studies.     

Antidisialosyl antibodies in chronic idiopathic ataxic neuropathy

Antidisialosyl antibodies were found in two out of 13 patients with chronic idiopathic ataxic neuropathy (CIAN) and not in 32 patients with different sensory neuropathies of known cause. This finding confirms the association of antidisialosyl antibodies and CIAN regardless of the absence of the M band. These antibodies may have pathogenic relevance; however, larger series are needed to establish their clinical significance.     

Antiganglioside antibodies in acute self-limiting ataxic neuropathy: incidence and significance

Antidisialosyl antibodies have been previously associated to chronic and acute ataxic neuropathies. We studied the presence of these antibodies in nine patients with acute self-limiting ataxic neuropathy (ASLAN) using ELISA and TLC immunodetection. One patient showed serum IgG immunoreactivity against gangliosides GD3 and GQ1b. The patient's IgG was able to bind to the nodes of Ranvier on frozen human dorsal root. Our studies confirmed that antidisialosyl reactivity is associated to ataxic neuropathy and its specific binding to the dorsal root could explain the predominant sensory involvement. Nevertheless, the low incidence of this reactivity indicates that a different pathogenic mechanism should be involved in most ASLAN patients.     

Sensory ataxic neuropathy and esophageal achalasia in a patient with Sjogren's syndrome

We describe a patient who developed an ataxic sensory syndrome associated with xerophthalmia and progressive dysphagia with regurgitation. Electrophysiological findings were consistent with an axonal sensory neuropathy, and superficial peroneal nerve biopsy showed a reduction in number of myelinated fibers with epineurial inflammation. Rheumatoid factor, anti-SSA/SSB and antinuclear antibodies were positive and a diagnosis of Sjogren's syndrome was made. An endoscopic investigation revealed esophageal achalasia. We suggest that there may be a common autoimmune mechanism directed to different targets on the basis of this rare association.     

Apoptosis of primary sensory neurons in GD1b-induced sensory ataxic neuropathy

Experimental autoimmune sensory ataxic neuropathy was induced in three of six rabbits sensitized with GD1b ganglioside (GD1b-SAN). TUNEL assay was performed on sections of dorsal root ganglia in the cauda equina. The results showed the presence of TUNEL-positive neurons in all three rabbits affected with GD1b-SAN. In contrast, no such neurons were observed in any of the sections from the unaffected rabbits that had been inoculated with GD1b, rabbits inoculated with adjuvant alone or those without inoculation. These data support that an apoptotic mechanism is involved in the pathogenesis of GD1b-SAN.     

Chronic idiopathic sensory ataxic neuropathy: immunological aspects of a series of 17 patients.

Sensory ataxic neuropathies (SANs) are characterized by loss of proprioceptive sensations and preservation of muscle strength. They may be idiopathic or associated with different toxic, infectious or autoimmune causes. Reactivity against gangliosides containing disialosyl groups, particularly GD1b, has been reported in isolated cases of acute and chronic idiopathic ataxic neuropathies (iSAN) and different experimental findings (in vivo animal models and in vitro preparations) suggest that antidisialosyl or antiGD1b antibodies could play a role in the pathogenesis of some ataxic neuropathies. We present the clinical, immunological and immunohistochemical characteristics of 17 patients who had a chronic iSAN without gammopathy. Patients were selected from a large group of 130 subjects with SAN: 93 with known etiology and 37 with iSAN. IgM and IgG antibodies to GM1, GM2, GM3, aGM1, GD1a, GD1b, GD3, GT1b and GQ1b were investigated by ELISA (INCAT protocol) and thin layer chromatography. Immunohistochemistry, using biotinylated Ig extracted from the patientś serum, was performed on human dorsal root ganglia (DRG), spinal cord, anterior and posterior roots, sural nerve and muscle tissue. The mean age of the 17 patients was 62 (37-80 years). The most disabling features were unsteadiness and severe ataxia of gait. Only one patient of this group was wheelchair-bound. The clinical data of these 17 patients were similar to those of the other patients with SAN, except that progression was slower. Antibodies to GD1b, GD3 and GT1b were found in 1/17. Two more patients (one with an acute iSAN and one with chronic iSAN and gammopathy), also had antibodies to disialosyl or GD1b. No immunohistochemical pattern of reactivity was found in any of the tissues tested with the 17 sera. In summary, this study demonstrates antidisialosyl or anti GD1b antibodies only in 3/37 (8.1p. cent) of patients with iSAN, either acute, chronic, or with gammopathy. However, their value seems to be reinforced by the negativity of antiganglioside antibodies in the large group of patients with SAN of known etiology (0/93). Further studies will be necessary to confirm the importance of target antigens containing disialosyl moieties in a subset of iSAN patients. However, the negativity of antiganglioside antibodies in most cases suggests that the pathology of the sensory neurons and/or axons is probably not humorally mediated in the majority of patients with iSAN.     

维生素B12与丁咯地尔治疗糖尿病周围神经病变临床观察

目的 观察维生素B12、丁咯地尔对糖尿病周围神经病变患者症状缓解和神经传导速度的影响.方法 116例周围神经病变患者分为治疗组和对照组,分别给予维生素B12、丁咯地尔和前列腺素E1静滴,给药前及给药2周后观察症状缓解情况和四肢神经传导速度. 结果 给药2周后,对照组各神经传导速度均明显增快(P<0.01),治疗组各神经传导速度亦增快(P<0.01),治疗组与对照组比较差异无统计学意义(P>0.05).治疗组总有效率为80.0%,对照组为89.3%,2组比较差异无统计学意义(P>0.05).结论 维生素B12、丁咯地尔治疗糖尿病周围神经病变具有较好的安全性和有效性.     

Balance exercise in patients with chronic sensory ataxic neuropathy: a pilot study

Although exercise therapy is considered part of the treatment of neuropathic patients, and somatosensory input is essential for motor learning, performance and neural plasticity, rehabilitation of patients with sensory ataxia has received little attention so far. The aim of this prospective pilot study was to explore the short‐ and medium‐term efficacy of a 3‐week intensive balance and treadmill exercise program in chronic ataxic neuropathy patients; 20 consecutive patients with leg overall disability sum score (ODSS‐leg) ≥2, absent/mild motor signs, clinical and therapeutic stability ≥4 months were enrolled. Evaluations were done at baseline, at the end of treatment and at 3‐ and 6‐month follow‐up. Outcome measurements included: ODSS‐leg, Berg balance scale, 6‐min walk distance, and the functional independence measure (FIM) scale. The short‐form‐36 health status scale (SF‐36) was used to measure health‐related quality of life (HRQoL). ODSS‐leg improved significantly compared with baseline, 3 weeks, 3 months (primary outcome), and 6 months follow‐up. A significant improvement in all functional secondary outcome measurements and in some SF‐36 subscales was also observed. This pilot study suggests that balance exercise is safe and well tolerated and might be effective in ameliorating disability and HRQoL in patients with chronic peripheral sensory ataxia.     

Incidence of endemic ataxic polyneuropathy and its relation to exposure to cyanide in a Nigerian community

BACKGROUND: The occurrence of ataxic polyneuropathy in an endemic area in south west Nigeria has been attributed to exposure to cyanide from cassava foods. However, it has been shown that the prevalence of ataxic polyneuropathy is not high in several communities in the tropics where exposure to cyanide from cassava foods is high. OBJECTIVES: To determine the incidence of ataxic polyneuropathy in an endemic community, and to compare the intake of cassava foods, exposure to cyanide, and levels of thiols in cases and controls. METHODS: A cohort of 3167 healthy subjects aged 10 years and over in Ososa, Nigeria, was followed for two years, screened, and examined neurologically. Ataxic polyneuropathy was diagnosed if sensory polyneuropathy and sensory gait ataxia were both present. Controls were selected randomly within 10 year age groups of subjects who screened negative. Intake of cassava foods, exposure to cyanide, concentrations of thiols (glutathione, cysteine, and gamma glutamylcysteine) in plasma, and visual evoked potentials were measured. RESULTS: Person-years of follow up were 6246 for 1469 male and 1698 female subjects in the cohort. The incidence of ataxic polyneuropathy was 64 per 10,000 person-years (31 for male and 93 for female subjects). Multivariate odd ratios were 0.78 (95% CI 0.23 to 2.61) for intake of the commonest cassava food, and 1.64 (0.56 to 5.09) for concentration of thiocyanate in plasma. The concentration of thiols was less than the reference limits in two controls, but in none of the cases. The latency of P100 was prolonged in 20 cases (69%) compared with 14 controls (42%) (p<0.05). CONCLUSIONS: The incidence of ataxic polyneuropathy is high in Ososa, Nigeria, but the intake of cassava foods, exposure to cyanide, and levels of thiols, are not related to the occurrence. These findings do not suggest that cyanide is the cause of endemic ataxic polyneuropathy.     

SIADH in a patient with sensory ataxic neuropathy with anti-disialosyl antibodies (CANOMAD)

Journal of Neurology -     

Dorsal-roots enhancement and Wallerian degeneration of dorsal cord in the patient of acute sensory ataxic neuropathy

Journal of Neurology -     

Vitamin B12 neuropathy is not due to failure to methylate myelin basic protein

It has been proposed that the biochemical lesion in subacute combined degeneration of the cord due to vitamin B12 deficiency, is impaired methylation of residue 107 (arginine) in myelin basic protein. We have examined myelin basic protein in brains of rats in which vitamin B12 was inactivated by exposure to nitrous oxide for up to 7 days. In addition brains of fruit bats in which vitamin B12 neuropathy had been produced by feeding washed, and hence vitamin B12-free fruit, were examined. There was no difference in the methylation of arginine 107 in myelin basic protein in these animals as compared to healthy control animals. Rats given an inhibitor of transmethylation reactions (cycloleucine) showed the expected fall in methylation of myelin basic protein.