Paraplegia 32 (1994) 193-195 © 1994 International Medical Society of Paraplegia

New findings and symptomatic treatment for , a disease occurring in North West

A Haque MD,! M Hossain MD,! JK Khan DPharm,2 YH Kuo PhD,2 F Lambein PhD,2 J De Reuck MD3

I Department of , Institute of Postgraduate Medicine and Research, Dhaka, Bangladesh; 2 Laboratory of Physiological Chemistry, Faculty of Medicine, University of Ghent, KL Ledeganckstraat 35, B-9000, Gent, Belgium; 3 Department of Neurology, Faculty of Medicine, University of Ghent, De Pintelaan 185, B-9000, Gent, Belgium.

Neurolathyrism is a form of spastic paraparesis caused by the neuroexcitatory 3-N-oxalyl-L-2,3-diaminopropanoic acid (f3-0DAP) present in the seeds and foliage of sativus. The disease is irreversible and usually nonprogressive. Tolperisone HCI, a centrally acting muscle relaxant, has been shown to reduce significantly the spasticity in neurolathyrism patients. Sporadic occurrence of HTLV-l infection (0.9% ) and of was found among the neurolathyrism patients. Osteolathyrism is linked to the consumption of the green shoots of .

Keywords: neurolathyrism; Lathyrus sativus; HTLV-I; osteolathyrism; tolperisone HCI; motor neuron disease.

Introduction of these patients were affected during the epidemic of 1970-74. Patients were selected Neurolathyrism is a motor neuron disease for treatment with tolperisone HCI (Mydo­ caused by overconsumption of the seeds of calm, chemical name: 2,4-dimethyl-3-pipe­ Lathyrus sativus, 1 a pulse grown and con­ ridinopropiophenone, Gedeon Richter, sumed in some Asian and African countries. Budapest, Hungary) along with controls. A The most recent epidemics occurred be­ permuted block randomisation chart was tween 1970 and 1974 in Bangladesh, China, followed, taking z value of 8, sample size of Ethiopia and . The disease affects 40. The study was conducted for a period of pyramidal cells and tracts leading to an 3 months. The parameters followed for irreversible condition.2 The respons­ symptoms were flexor spasm, muscle ible is the neuroexcitatory nonprotein cramp, repeated fall, heavy legs, startle amino acid 3-N-oxalyl-L-2, 3-diaminopropa­ attack, automatic clonus, stiffness of adduc­ noic acid (f3-0DAP, sometimes referred to tor muscles, stiffness of Achilles tendon, as f3-oxalylamino-alanine or BOAA) which speed of walk. The signs that were con­ is structurally and neuropharmacologically a sidered are tone, tendon reflexes, clonus glutamate analog. The green shoots of L. and power. sativus contain an additional and An ELISA test (Vironostika HTL VII 92 an osteotoxin.J Most of the patients develop T) from Organon Technica (Turnhout, heavy legs, spasms of the muscles of the legs Belgium) was used to detect HTLV-l anti­ and spasticity. At present there is no treat­ bodies in serum and cerebrospinal fluid. ment available for neurolathyrism.

Methods Results We have diagnosed 882 neurolathyrism pa­ tients recorded in three districts in Rajshahi In about 30% of the patients examined the Division of North West Bangladesh. Most disease has been progressing for the last 4-6 194 Haque et al Paraplegia 32 (1994) 193-195 years after about 15 years of static condi­ reduces the convulsive effect of electro­ tion, even after discontinuation of consump­ shock and has a marked anti nicotinic activ­ tion of L. sativus. The follow up study after ity. Tolperisone HCI also has an inhibitory the patients had been on a dose of effect on muscle contraction.4 150 mg/day of tolperisone HCI in divided In some patients affected by tropical dose for a period of 3 months indicated spastic paraperesis (TSP), a disease compar­ improvement of varying degrees in all the able to neurolathyrism, an association with symptoms mentioned. Among the patients HTLV-1 was observed.s In Ethiopia, Hai­ treated 60% had normal tone after 3 manot et al examined 115 neurolathyrism months. In 70% of the patients who had patients for HTLV-1 association, with nega­ spontaneous clonus before treatment, this tive results.6 We examined 444 patients for symptom disappeared whilst in the other the presence of antibodies against HTLV-1. patients its occurrence was drastically re­ Four patients were found to be seropositive. duced. The time to walk 100 meters de­ Although HTLV related myelopathy has creased for all treated patients but for none sensory symptoms, no such symptoms were of the control group. All treated patients observed in the above patients, who perhaps had increased power and improved physical may be considered as carriers only of the abilities. virus. This should not be surprising con­ Four patients out of 444 patients tested sidering the low rate of HTLV -I-associated for HTLV-1 infection were seropositive. myelopathy in relation to the seropreval­ In a radiological survey of 60 neuro­ ence of HTL V- J.7 Because of this low patients, who had skeletal defor­ pre valance of HTL V-I infection we can mity and who had developed the disease state that this virus cannot be responsible before the age of 18 years, it was found that for the spastic paraparesis attributed to two patients had lack of union of ossification neurolathyrism in Bangladesh. centres of vertebrae and pelvis, indicative of It is known that (3- osteolathyrism (details to be published sep­ (BAPN) present in L. odoratus can produce arately). the -deforming osteolathyrism by in­ hibiting the cross-linking in and elastin.8 Cohn & Streifler had also reported the occurrence of minor skeletal lesions in Discussion neurolathyrism patients.9 L. sativus does Although the disease is supposed to be not contain free BAPN but Lambein & epidemic in nature, 2% of the cases were coworkers detected an unstable isoxazoli­ affected before the epidemic of 1970-74 and none derivative (2-cyanoethyl-isoxazolin-5- 7% of the cases were affected after the one) in the shoots of L. sativus that can be epidemic, suggesting that the disease can metabolised into BAPN and produce osteo­ 111.11 also occur sporadically. It should be men­ lathyrism in experimental animals. The tioned that in the afflicted areas most people concentration of this osteotoxin in the seed­ also consume the green shoots as a veget­ lings of different varieties of L. sativus able, unaware of the in the shoot. seems not to be correlated to the concentra­ These patients also have some degree of tion of the neurotoxin in the seeds.' As the wasting of the small muscles of legs which is green shoots of L. sativus are a popular difficult to explain by disuse only. vegetable in L. sativus growing areas of There has been no radical treatment for Bangladesh, we suggest that this habit may neurolathyrism patients reported. To our be associated with osteolathyrism, which in knowledge the only symptomatic treatment many cases might remain undiagnosed. The that is available in an experimental stage is a two cases identified as clinical osteolathy­ surgical incission in the aductor muscles to rism are the first reports on the occurrence release contracture (Dwivedi & Spencer, of osteolathyrism in Bangladesh. Further personal communication). Tolperisone HCl surveys might indicate a different susceptib­ inhibits multisynaptic reflex activity and ility to osteolathyrism as compared to that reduces strychnine induced hyperreflexia. It to neurolathyrism. Paraplegia 32 (1994) 193-195 New findings in neurolathyrism 195

Acknowledgement

This work was supported by a Bangladeshi Belgian Authority for Development Coopera­ Belgium interuniversity project, financed by the tion.

References

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