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Konzo: a Distinct Disease Entity with Selective J Neurol Neurosurg Psychiatry: First Published As 10.1136/Jnnp.56.6.638 on 1 June 1993

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Konzo: a Distinct Disease Entity with Selective J Neurol Neurosurg Psychiatry: First Published As 10.1136/Jnnp.56.6.638 on 1 June 1993 63868ournal ofNeurology, Neurosurgery, and Psychiatry 1993;56:638-643 Konzo: a distinct disease entity with selective J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.6.638 on 1 June 1993. Downloaded from upper motor neuron damage T Tylleskar, W P Howlett, H T Rwiza, S-M Aquilonius, E Stalberg, B Linden, A Mandahl, H C Larsen, G R Brubaker, H Rosling Abstract Histories were taken and neurological Two Tanzanian patients with konzo were examinations were carried out on both severely disabled by a non-progressive patients during visits in their homes in May spastic paraparesis, since the sudden 1985 and repeated in 1986, 1988 (WPH), onset during an epidemic six years ear- and again in Sweden in 1991 (S-M A). lier. At the time of onset they had a high Magnetic resonance imaging (spin echo) of dietary intake of cyanide from exclusive the brain and spinal cord was performed with consumption of insufficiently processed a Philips T5 MR-scanner (05 Tesla unit) bitter cassava roots. MRI of brain and without use of intravenous contrast. Ti spinal cord were normal but motor weighted, proton density, and T2 weighted evoked potentials on magnetic brain images were obtained in sagittal, coronal, and International Child Health Unit, stimulation were absent, even in the only axial planes of the brain and in the sagittal Department of slightly affected upper limbs. Other neu- plane of the whole spinal cord. Axial proton Pediatrics, University rophysiological investigations were density and T2 weighted images over the Hospital, Uppsala, Sweden largely normal but the more affected conus medullaris were also obtained. T Tylleskar patient had central visual field defects. Neurophysiological investigations were H Rosling Konzo is a distinct disease entity with performed with conventional techniques Kilimanjaro Christian selective type upper motor neuron dam- including motor and sensory nerve conduc- Medical Center, age. tion, small fibre tests such as respiratory Moshi, Tanzania W P Howlett dependent heart rate variation,4 thermal per- Department of (7 Neurol Neurosurg Psychiary 1993;56:638-643) ception thresholds for warmth and cold and Internal Medicine, pain threshold for heat and cold; concentric Muhimbili Medical electromyography (EMG) both at rest, at Center, Dar-es- maxi- Salaam, Tanzania Konzo is an upper motor neuron disease, slight voluntary contraction and during H T Rwiza characterised by abrupt onset of a varying mal contraction (automatic turn/amplitude Department of degree of symmetrical, isolated, and perma- analysis,5 single fibre EMG, fibre density Neurology, University nent but non-progressive spastic paraparesis. measurement, jitter analysis, blink reflexes, Hospital, Uppsala, It was first described in Zaire in 1938 and is electroenchephalography (EEG), somatosen- Sweden S-M Aquilonius named after the local designation in the first sory evoked potentials (SEP), full field visual and brainstem http://jnnp.bmj.com/ Department of report.' In the last decade it has been evoked potentials (VEP), Clinical reported from remote rural areas of evoked response audiometry (BERA). Neurophysiology, Mozambique, Tanzania, and Zaire. The uni- Transcranial stimulation of the motor cortex University Hospital, and clinical was performed with a magnetic stimulator to Uppsala, Sweden form epidemiological findings E Stalberg have identified konzo as a distinct disease elicit motor evoked potentials (MEP). Department of entity induced by a combined effect of high Stimulation was also performed over the C7 Radiology, Falun cyanide and low sulphur intake from exclu- vertebra. Pure tone audiometry and caloric Hospital, Falun, sive consumption of insufficiently processed stimulation of the vestibularis were studied in Sweden on September 29, 2021 by guest. Protected copyright. B linden bitter cassava roots.2 The study of konzo has conventional ways. Electronystagmography been limited to clinical examinations (ENG) in a dark room supervised by an Department of formerly Ophthalmology, during field surveys. infrared camera was used for the registration University Hospital, of spontaneous nystagmus, head shake nys- Uppsala, Sweden tagmus, positional nystagmus, and gaze nys- A Mandahl Subjects and methods tagmus at 300 eye deviation. Smooth pursuit Department of Audiology, University Two male konzo patients aged 25 and 19 movements of 600 with a fixed velocity of Hospital, Uppsala, years were invited to Sweden in October 20°/s 10 movement to the right and 10 to the Sweden 1991. They were diagnosed in 1985 during left was recorded with ENG and analysed by H C Larsen an epidemic in Tarime district,"3situated east computer for velocity, accuracy, and superim- Shirati Hospital, of Lake Victoria in the northern part of posed saccades according to standardised Musoma, Mara Region, Tanzania Tanzania. procedure.6 Voluntary saccades (that is, rapid G R Brubaker The study was approved by the ministry of eye movements) of 600 was performed 20 Correspondence to: health of Tanzania and the ethical committee times to the right and 20 times to the left Dr T Tylleskiir, International Child Health of Uppsala University. Local civil and health analysed by computer for start latency, accu- Unit (ICH), Departnent of authorities informed the patients and their racy, and velocity.6 Pediatrics, University Hospital, S-751 85 Uppsala, families about the aim and procedures to be Conventional ophthalmological investiga- Sweden. undertaken and obtained written consent tions included: visual acuity, eye pressure, Received 18 May 1992 from the patients to participate. A local direct/consensual pupillary reflex, corneal and in revised form 16 October 1992. health worker accompanied the patients to sensitivity, colour vision, dark adaptation, Accepted 28 October 1992 Sweden and acted as interpreter. and binocularity. Visual fields were examined Konzo: a distinct disease entity with selective upper motor neuron damage 639 with Goldmann perimetry. The ocular fundi months. He is able to move around with a J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.6.638 on 1 June 1993. Downloaded from were photographed and scrutinised for four point walking frame and he makes his defects in the nerve fibre layer. living as a shoe maker. Serum thiocyanate was used as biomarker In the month preceding the onset the fam- for dietary cyanide exposure.2 An extensive ily was almost exclusively eating cassava, the battery of haematological and biochemical only crop to survive the drought in 1985. His routine analyses were carried out including youngest brother, born in 1973, was similarly analyses of blood cells, platelets, haemoglo- but less severely affected in March 1985. bin, serum levels of electrolytes, different pro- teins, enzymes, vitamin B6, B12, thyroid PATENT 2 hormones, a plasma electrophoresis, and rou- This man was born in 1972 as the fifth born tine urine tests. Serological testing included: in a family of 12 children. There was no fam- IgM anti-hepatitis A virus, hepatitis B surface ily history of neurological disorder. He was antigen, anti-hepatitis C virus, antibodies to healthy until March 1985 when one night he syphilis, retroviruses HIV-1 + 2 (Enzygnost noticed weakness in both legs while walking AntiHIVi + 2 EIA, Wellcosyme Recom- to the latrine. He returned to bed with diffi- binant HIV-1 EIA, PCR HIV-1), HTLV-I culty but in the morning he was unable to (Abbot HTLV-I EIA, PCR HTLV-I). stand, and over the next three days the weak- Characterisation of lymphocyte subpopula- ness increased and he was unable to get out tions by immunofluorescence and flow of bed. At this stage he also experienced diffi- cytometry as well as an attempt to isolate culties in speaking, visual disturbances and HIV-1 and HTLV-I from blood specimens some tingling sensations in his legs, and a was performed. Direct microscopy of faeces cold feeling in his feet. He also experienced was performed for cysts and eggs of intestinal clumsiness in his hands. He improved over parasites and direct microscopy of blood films some weeks and since May 1985 he is able to for malaria parasites, trypanosomes, and stand and to walk with the help of two sticks. filaria. ELISA serology for amoeba, His hoarseness cleared and his vision echinococcus, filaria, schistosoma, and improved. immunofluorescence for leishmania, try- At the time of onset of the paralysis the panosomes, giardia, and malaria was per- diet of the family consisted almost exclusively formed. The cerebrospinal fluid was screened of cassava because of drought. Out of the for syphilis and examined for cells, protein, total household of two parents and eight liv- glucose, and lactate. A protein electrophoresis ing children four other siblings aged 6, 11, 12 and an isoelectric focusing was done. and 14 were similarly affected in March-April 1985. The only three to escape the disease were the oldest child who was away at a Results boarding school, the youngest who was still PATIENT 1 breast-feeding, and a four year old boy. This man was born in 1966, the eldest of three children. There was no family history of CLINICAL FINDINGS* neurological disorder. He was healthy until Figure 1 shows the two patients in October the 16 March 1985. The night before the 1991, six years after onset. The clinical find- http://jnnp.bmj.com/ onset of his illness he attended a local dance ings from the initial examination in May and experienced no difficulties with his legs. 1985, six weeks after the onset, and the Later that night at home on the way to the examination in October 1991 were almost latrine he noticed a weakness of the legs. The identical. Both patients were unable to walk following morning the weakness was more unaided because of severe spastic paraparesis. pronounced and the legs were trembling on The degree of disability on the expanded dis- standing. He also experienced some sensa- ability status scale (EDSS) was rated at 7-0 on September 29, 2021 by guest. Protected copyright. tions in the legs, and felt "as if the skin was for patient 1 and 6-5 for patient 2.
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