Neurol Sci (2007) 28:205208 DOI 10.

1007/s10072-007-0822-0 C A S E R E P O RT

A. Ammendola E. Ammendola F. Argenzio G. Tedeschi

Clinical and electrodiagnostic follow-up of an adolescent poisoned with thallium

Received: 5 March 2007 / Accepted in revised form: 21 June 2007

Abstract We report a six-year clinical and electrodiagnostic follow-up of an adolescent patient with acute thallium poisoning from attempted suicide. During the acute stage the patient showed gastrointestinal disturbances, alopecia, and clinical and electrodiagnostic signs of severe polyneuropathy. Three years after poisoning, his neurological symptomatology was making progress, and electrophysiologic signs of peripheral neuropathy were mainly confined to lower limbs. Six years after intoxication, he was still complaining of weakness and sensory disturbances at the level of distal lower extremities; his neurologic and electrodiagnostic abnormalities affected mainly the feet. In this case report we underline the importance of early diagnosis and treatment to prevent neurological damage and the role of serial electromyographic and nerve conduction studies in thallium poisoning. These investigations allowed the authors to depict the electrophysiologic course of peripher-

al nervous system involvement over six years following poisoning. Key words Thallium poisoning Electrophysiologic follow-up

Peripheral neuropathy

Introduction Thallium poisoning, resulting from accidental ingestion or from attempts at homicide or suicide, is relatively rare [14]. Initial clinical features are gastrointestinal disturbances (nausea, vomiting, epigastric pain, diarrhoea) followed by neurologic manifestations involving the peripheral (sensorimotor neuropathy) and/or central (confusion, convulsions, psychosis, choreiform movements) and/or autonomic (tachycardia, hypertension, dry skin) nervous systems. Skin lesions are commonly present (loss of hair, eruptions and atrophic changes of skin). In severe cases, cranial nerve involvement may also be present. With massive doses, coma and death may occur [5]. We report the case of an adolescent who had severe peripheral neuropathy induced by thallium poisoning, in whom clinical and electrophysiological data were obtained over a period of six years from toxic ingestion.

A. Ammendola () G. Tedeschi Department of Neurological Sciences Second University of Naples Piazza Miraglia 2, I-80138 Naples, Italy e-mail: angelo.ammendola@unina2.it E. Ammendola Clinic of Child Neuropsychiatry Second University of Naples, Naples, Italy F. Argenzio Department of Clinical Toxicology Second University of Naples, Naples, Italy G. Tedeschi Institute Hermitage Capodimonte Naples, Italy

Clinical case A 16-year-old patient, suffering from non-pharmacologically treated anxiety and depressive disturbances, attempted suicide by ingesting some grains of zelio (a rodent and ant poison) containing 1.3 g of thallium sulphate. Three days after the ingestion of the toxic metal, the patient was hospitalised because of severe lower limb pains, abdominal cramps and breathing difficulties. Complete

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loss of hair occurred during the second week of the illness. Three weeks after poisoning the patient appeared weak, tired, dyspnoeic and tachycardic, with dry skin and alopecia. A neurologic examination was characterised by severe and widespread hyperalgesia, distal tremor of the upper limbs, diffuse muscle weakness and atrophy, with absent tendon reflexes and sensory deficit mainly involving the lower limbs. Cranial nerves were not involved; in particular, although a VEP study was not performed, symptoms and/or clinical signs of optic neuropathy were not found. The electroencephalogram revealed mild generalised slowing in the theta range without focal abnormalities and CT scan was unremarkable. The clinical picture suggested thallium poisoning, which was confirmed by the presence of a high concentration of thallium in the urine (3.4 mg/l). Nerve and/or cutaneous nerve biopsy were not accepted by patient. Other causes of neuropathy were ruled out, and the sensorimotor neuropathy was attributed to thallium intoxication. An appropriate regimen of diuretics and Prussian blue was started. After three months neurologic examination showed: normal consciousness, loss of upright position, inability to walk, diffuse hyperalgesia and sensory loss involving all sensory modalities with glove-and-stocking distribution, motor weakness (according to the Medical Research Council [MRC] manual, muscle score was 5/5 in proximal
Table 1 Main findings of electromyographic follow-up of patient Muscles 3 months after poisoning Abnormal spontaneous activity EDB, L and R AH, L and R Fibrillation+++ Fibrillation+++ Voluntary activity

and 4/5 in distal upper limbs; 3/5 in proximal and 0/5 in distal lower extremities), muscle atrophy (greater in lower than upper limb muscles and more severe distally) and absent lower limb tendon reflexes. At the same time, electromyography (extensor digitorum brevis, abductor hallucis, tibialis anterior, vastus lateralis and abductor digiti V muscles on both sides) and nerve conduction studies (peroneal, posterior tibial, sural and median nerves bilaterally), performed with skin temperature maintained above 34C by a thermostat infrared lamp, showed findings compatible with a diffuse axonal degeneration of sensory and motor nerve fibres, more severe in distal lower limbs (Tables 1 and 2). After discharge from the hospital, the patient underwent periodic neurologic examinations while electrodiagnostic tests (performed on the same muscles and nerves) were performed at three and six years after toxic ingestion. Three years after poisoning, during which the patient underwent continuous pharmacological and physiotherapeutic treatments, hair returned to normal and motor and sensory functions of limbs improved, as well as neurologic examination. Walking was possible with the assistance of ankle-foot orthoses; motor deficit (MRC manual muscle score was 5/5 in upper limbs, 4/5 in proximal and 0/5 in distal lower extremities) and muscle atrophy only persisted in lower limbs with increased severity at distal level.

3 years after poisoning Abnormal spontaneous activity Fibrillation++ Fibrillation++ Voluntary activity

6 years after poisoning Abnormal spontaneous activity No No Voluntary activity

Absence Absence

Absence Absence

Absence Severe loss of MU; long duration, polyphasic MUAP Moderate loss of MU; long duration, highamplitude MUAP Moderate loss of MU; long duration, highamplitude MUAP No loss of MU; long duration, high-amplitude MUAP

TA, L and R

Fibrillation+++

Absence

Fibrillation++

Absence

No

VL, L and R

Fibrillation+++

Moderate loss of MU; long duration, highamplitude MUAP

No

Moderate loss of MU; long duration, highamplitude MUAP

No

ADV, L and R

Fibrillation+++

Slight loss of MU; Fibrillation++ long duration, highamplitude MUAP

Slight loss of MU; No long duration, highamplitude MUAP

EDB, extensor digitorum brevis; AH, abductor hallucis; TA, tibialis anterior; VL, vastus lateralis; ADV, abductor digit V; R, right; L, left; MU, motor units; MUAP, motor unit action potentials; ++, moderate numbers of fibrillations in 3 or more regions of the muscle; +++, many fibrillations in all regions of muscle

A. Ammendola et al.: Adolescent poisoned with thallium Table 2 Main findings of nerve conduction follow-up of patient 3 months after poisoning Conduction Evoked potential velocity amplitude (m/s) Motor nerves Peroneal (HF-A) Posterior tibial (PF-MM) Median (E-W) Sensory nerves Posterior tibial (TI-MM) Sural (LM-S) Median (DIII-W) 3 years after poisoning Conduction velocity (m/s) Evoked potential amplitude 6 years after poisoning Conduction velocity (m/s)

207

Evoked potential amplitude

L=47.0 R=48.5

Absence bilaterally Absence bilaterally L=4.3 mV R=5.2 mV Absence bilaterally L=1.5 V R=1.0 V L=3.5 V R=3.0 V

L=48.5 R=48.0

Absence bilaterally Absence bilaterally L=5.8 mV R=6.2 mV Absence bilaterally L=1.8 V R=1.5 V L=6.0 V R=5.7 V

L=50.8 R=49.5

Absence bilaterally Absence bilaterally L=6.0 mV R=6.8 mV Absence bilaterally L=2.0 V R=1.7 V L=6.1 V R=5.8 V

L=40.5 R=41.6 L=38.6 R=37.4

L=42.8 R=43.0 L=43.6 R=42.2

L=43.2 R=43.0 L=45.5 R=44.6

HF-A, head fibula-ankle; PF-MM, popliteal fossa-medial malleolus; E-W, elbow-wrist; TI-MM, toe I-medial malleolus; LM-S, lateral malleolus-sura; DIII-W, digit III-wrist; R, right; L, left

Electrophysiologic study showed normal electroencephalography and electrodiagnostic findings compatible with the persistence of sensorimotor polyneuropathy (Tables 1 and 2). Six years after intoxication, the patient complained only of weakness and sensory disturbances at the level of the feet. At this time, his walking was possible without ankle-foot orthoses, flexion and extension of toes were difficult bilaterally and light touch evoked complaint of burning pain from the feet. Neurologic examination showed bilateral distal weakness (MRC manual muscle score was 5/5 in upper limbs, 4/5 in proximal and 0/5 to 3/5 in distal lower extremities), moderate in tibialis anterior and gastrocnemius muscles and severe in toes flexor and extensor muscle groups; bilaterally attenuated patellar and achilles reflexes; and feet hypoaesthesia involving all sensory modalities, with painful paraesthesias. Electrodiagnostic study showed signs of electrophysiologic improvement compared to previous investigations: voluntary activity of distal lower limb muscles was improved bilaterally, and median and sural response amplitudes were increased on both sides.

Discussion An early characteristic of acute thallium intoxication is the involvement of the peripheral nervous system, consisting of a dying back axonal degenerative process involving sensory and motor fibres [6, 7]. Axonal degeneration may be attributable to dephosphorylation of the Na/K-activated ATPase induced by thallium ions, which take the place of potassium ions in this enzymatic complex, due to a tenfold higher affinity compared to potassium ions [8].

Although the progression of clinical involvement in thallium poisoning has been described in a number of cases, serial nerve conduction and electromyographic studies have rarely been documented. Yokoyama et al. [9] assessed the effects of thallium on the conduction velocities of faster and slower nerve fibres in a patient with acute thallium poisoning at two and eleven months from symptom onset. They concluded that in the early stage of intoxication the conduction velocities of faster fibres are significantly decreased and then they slowly return to normal, while those of slower fibres are minimally affected and quickly improve. Dumitru and Kalantri [10] described electrodiagnostic abnormalities of plantar nerves in a patient 24 months after symptom onset. The authors diagnosed a primarily distal axonopathy, affecting the lower more than upper extremities, and requiring more than two years for recovery. In our case report the 3month follow-up revealed the absence of voluntarily activated motor units in extensor digitorum brevis, abductor hallucis and tibialis anterior bilaterally (Table 1). Additionally, peroneal motor, posterior tibial motor and posterior tibial sensory responses could not be elicited on either side (Table 2). The electromyographic findings demonstrated the typical evolution of an acute axonal damage and were stabilised over the 6-year follow-up. On the other hand, nerve conduction studies showed that normalisation did not occur in any nerve while the baseline data slightly improved only for the median nerve, with the improvement occurring mainly between the first and the second examination. The presence of electrodiagnostic signs of nerve damage 6 years after acute thallium poisoning at the level of the lower extremities is most likely due to a more difficult recovery of distal extremity muscles and nerve segments. Finally, it is noteworthy to underline that in our case report the diagnosis was made after three weeks, and early diagnosis and treatment (within 72 h) is important to prevent neurological damage [11].

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To summarise, neurologic and electrophysiologic follow-up of an adolescent poisoned with thallium was examined, and the role of serial electromyographic and nerve conduction studies is discussed. This case report reminds us of the importance of early diagnosis and treatment to prevent neurological damage and his serial electrodiagnostic investigations allowed the authors to depict the electrophysiologic course of peripheral nervous system involvement over six years following thallium poisoning.

References
1. Desenclos JC, Wilder MH, Coppenger GW et al (1992) Thallium poisoning: an outbreak in Florida, 1988. South Med J 85:12031206 2. Gergont A, Lankosz-Lauterbach J, Pietrzyk JJ, Kacinski M (2004) Nervous system involvement in three children poisoned with thallium. Przegl Lek 61:371373 3. Lukacs M (2003) Thallium poisoning induced polyneuropathy clinical and electrophysiological data. Iddeggyogy Sz 56:407414 4. Nordentoft T, Andersen EB, Mogensen PH (1998) Initial sensorimotor and delayed autonomic neuropathy in acute thallium poisoning. Neurotoxicology 19:421426 5. Windebank AJ (1993) Metal neuropathy. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 3rd edn. WB Saunders Co, Philadelphia, pp 15491570 6. Cavanagh JB, Fuller NH, Johnson HRM, Peter R (1974) The effects of thallium salts with particular reference to the nervous system changes. A report of three cases. Q J Med 43:293319 7. Davis LE, Standefer JC, Kornfeld M et al (1981) Acute thallium poisoning: toxicological and morphological studies of the nervous system. Ann Neurol 10:3844 8. Nielsen VK, Wright KC (1987) Toxic polyneuropathies. In: Brown WF, Bolton CF (eds) Clinical electromyography. Butterworth Publishers, Boston, pp 283303 9. Yokoyama K, Araki S, Abe H (1990) Distribution of nerve conduction velocities in acute thallium poisoning. Muscle Nerve 13:117120 10. Dumitru D, Kalantri A (1990) Electrophysiologic investigation of thallium poisoning. Muscle Nerve 13:433437 11. Pau PW (2000) Management of thallium poisoning. Hong Kong Med J 6:316318

Sommario Viene riportato uno studio clinico ed elettrodiagnostico di un giovane paziente con intossicazione acuta da tallio a scopo suicida, seguito per sei anni. Durante la fase acuta il paziente presentava disturbi gastrointestinali, alopecia, e segni clinici ed elettrofisiologici di una severa polineuropatia. Tre anni dopo lavvelenamento, la sua sintomatologia neurologica migliorava ed i segni elettrofisiologici di neuropatia periferica erano principalmente confinati agli arti inferiori. Sei anni dopo lintossicazione, il paziente lamentava ancora debolezza e disturbi sensitivi a carico dei tratti distali degli arti inferiori; dove persistevano segni neurologici ed elettrodiagnostici di danno neurologico. In questo caso noi evidenziamo limportanza di una diagnosi e trattamento precoci per prevenire il danno neurologico ed il ruolo degli studi elettromiografico e di conduzione nervosa nellavvelenamento da tallio. Queste indagini ci permettevano di descrivere il decorso elettrofisiologico del coinvolgimento del sistema nervoso e di confermare segni elettrodiagnostici di danno neurologico anche dopo sei anni dalla intossicazione.