Case report -.-.. -___ _.__ --- _. Acute systemic vanadate poisoning presenting as cerebrovascular &hernia with prolonged reversible neurological deficits (PRIND) Hans-Peter S&lake”?*, Hans Peter Bertramb, Ingo ~ilhe~ Husstedt” and Gerhard Schuierer” ‘Department of Neurosurgery, University of Wtirzburg, Josef-Schneider-Strujle II. D-97080 Wiirzburg. Germon); bltistitute of Pharmacology and Toxicology, ‘Department of’ Neurology, ‘Department of Radiology, L~niversit~~ qf Mtinster, D-481 49 punster German,v (Received 26 January, 1993) (Rev&d, received 26 April, 1993) (Accepted 30 September, 1993) Key words: Vanadium intoxication; Ammonium metavanadate; Na’,K’-ATPase Summary A 22-year-old woman is reported who attempted suicide by oral ingestion of approximately IO-15 g ammonium metavanadate (NH,VO,). A few hours later she developed gastrointestinal symptoms followed by a transient right sensomotor hemiparesis and aphasic disturbances. Brain MRI and SPECT with 99mTc-HMPA0 revealed a lesion in the left parietal cortex. Plasmapheresis, ascorbic acid and desferoxamine led to a complete clinical recovery within a few days. Vanadium (V), a metallic group Vb element (molecular weight 50.9) of the first transition series, is widely distributed in the environment, exerting various effects on enzymatic processes and biological membranes [l-7]. It is supposed to be an essential trace element in some higher animals, and probably in man [2,4,5]. Toxic effects have been described, mainly occurring in oil industry workers and miners after chronic inhalation of dust containing vanadium pentoxide (V,O,), which results from the combustion of petroleum and coal f6-lo]. These toxic effects chiefly include local inflammatory changes of mucous membranes, particularly of the respiratory tract. More recently, vanadium has also been postulated *Corresponding author. Fax: (+49 931) 201 2635. to play a role in the pathogenesis of manic depressive illness [11,12]. We report here a patient who developed transient hemiplegia and aphasia after oral ingestion of a single high dose of ammonium metavanadate. Case repuft A 22-year-old woman attempted suicide by oral intake of a spoonful (approximately lo-15 g) ammonium metavanadate (NH,VO,), which was available in her workshop place in the pharmaceutical industry (heparin production). After 2 h she developed gastrointestinal symptoms such as nausea, vomiting and diarrhoea. One hour later a right-sided brachiofacial paresis manifested, followed by a right hemihypesthesia and sensomotor paresis of the right lower limb as well as mixed amnestic and sensorimotor aphasia. 93 Fig. 1. T,-weighted axial MRI (TR = 2,800, T, = 90) showing a high-intensity signal lesion in the left parietal cortex (+) with slight edema (+) in the adjacent subcortical white matter (R = right, L = left). Thirty-six hours after vanadate intake only a pronation and drop tendency in the right arm and a slight amnestic aphasia were detectable. Physical examination was normal except for a green discoloration of the tongue and gums. Internal screening investigations such as ECG, chest X-ray and abdominal sonography were normal. Gastroscopy showed an acute erosive gastritis, which healed completely under antacid therapy. All routine laboratory tests revealed normal values except some parameters of blood coagulation. There was a decrease of prothrombin time to 32% (normal value: 70100%); the platelet count was 73 OOO/pl(n.v.: 150 OOO350 OOO/~I).Fibrinogen plasma levels fell to I. 18 g/l (n.v.: 1.70-4.10 g/l) 72 h after intoxication. PTT (partial thromboplastin time), thrombin time and antithrombin III were within normal range. After administration of 750 ml fresh frozen plasma all coagulation tests including platelet counts returned to normal values over the next 5 days. Urinalysis showed a erythrocyturia and leucocyturia, slight proteinuria, which subsided spontaneously. CSF protein was increased (1070 mgll) with normal cell counts. Brain T,-weighted MRI (TR = 2800: T, 1S/9) revealed a cortical and a subcortical area of increased signal intensity along the dorsal part of the sylvian fissure, the cortical lesions being more pronounced than those in the adjacent subcortical white matter (Fig. 1f. SPECT (370 MBq 99mTc-HMPAO) revealed localized hypoperfusion in the corresponding area. Electroencephalography (EEG) revealed distinct focal delta activity in the left parieto-temporal region. Central latencies of somatosensory evoked potentials (SEP) after tibia1 nerve stimulation were asymmetrical, yielding delayed latencies over the left sensory cortex (P,,: 43.9 msec) as compared to the right (PbO:38.0 msec). Visual and brainstem auditory evoked potentials as wellas SEP from the median nerve and motor evoked potentials (recorded from m. abductor pollicis brevis and m. tibialis anterior) showed bilaterally normal latencies. Nerve conduction velocities of median, peroneal and sural nerve were normal. Detoxification was based on data from animal experimental studies [13-171. Treatment included i.v. administration of desferoxamine mesylate (Desferal”) at a daily single dose of 500 mg and high oral doses of ascorbic acid (3 x 1.5 g/day), in order to reduce V” to less toxic V3+compounds, followed by plasmapheresis (plasma exchange 2100-2300 ml) at each of the following 3 days. Decadrone phosphate (3 x 8 mg/day) was given to prevent lung edema. Fig. 2 shows plasma and urine vanadium levels and +-plasma cont. pg V/ml El- urine 00°C. 16 0.61 ‘\ I \O I time (h) after V intake Fig. 2. Time course of vanadium (V) levels in plasma and urine in relation to detoxification therapy D = i.v. administration of a single dose of 500 mg desferoxamine mesylate (Desferal”) P = plasmapheresis. 94 their time course in relation to detoxification therapy, obtained by means of atomic emission spectroscopy; after 36 h the CSF vanadium level was ~20 p V/l. In non-exposed man normal values are 0.016.-0.939 ,ug V/l in plasma and ~1 ,ug V/l in urine [4]. All clinical symptoms subsided within 10 days. Follow-up during one year confirmed the complete recovery. Vanadium levels in plasma 3 and 9 months later showed normal values, whereas urinary vanadium content was still increased with 61.5 and 12.3 ,ug V/l, respectively. stand, how this acute intoxication caused a unilateral lesion. On the other hand, the observed cerebrovasculai manifestations occurred only few hours after vanadato ingestion. Except from a moderate nicotine abuse (about 5 cigarettes/day), there were no cerebrovascular risk factors perceptible in the patient’s personal or familiar history, i.e. there was no use of oral contraceptives other drug treatment. cerebral ischemia It seems blood Thus, an accidental with vanadate possible, coagulation that played poisoning the observed a primary or any coincidence of is unlikely. alterations of role in the patho- genesis of cerebrovascular ischemia - for instance. by stimulating fibrinogen activation and causing a disseminated intravasal coagulopathy. However, such effects Discussion have not been observed after acute or chronic in animal exposure The present case is, to our awareness, the first of acute vanadate poisoning in man. The clinical symptoms were unlike those of human cases with chronic vanadium exposure, in whom renal and cardiac disturbances as well as a decrease of blood cholesterol have been described [5,6]. With concern to the central nervous system, only slight and rather unspecific complaints (i.e. tiredness, giddiness and tremor) were observed in a few industrial workers after chronic exposure to vanadium and its compounds [8-IO]. Numerous animal experimental studies did not reveal any distinct neurological symptomatology after acute or chronic vanadate administration [ l-6,15]. Yet, these investigations showed vanadium compounds to exert a variety of in vivo and in vitro effects on enzymes and biological membranes [2,4-7,131. Vanadate (VO,)- and vanadyl (VO,)’ are very potent inhibitors of Na+,K+ATPase [ 11. Low vanadate concentrations stimulate membrane-bound adenylate cyclase and NADH oxidase, whereas high concentrations lead to enzyme inhibition [2,4,5]. In rat cerebral cortex, both vanadate and vanadyl stimulate phosphorylation of proteins and synaptic membranes, but cause a dose-dependent inhibition of mitochondrial phosphorylation [3]. The clinical symptoms and their course of the present case resemble those of a prolonged reversible ischemia (PRIND) in the area of supply of left middle cerebral artery. The MRI finding of an increased T,-weighted signal intensity in the corresponding cortical area is compatible with a vascular lesion. This view was supported by the detection of a focal hypoperfusion left-parietal in SPECT with the flow tracer g9mTc-HMPA0. Toxic substances usually produce acute bilateral cerebral and/or cerebellar symptoms. It is difficult to under- pounds. Altogether, pathomechanisms the exact experimental studies to vanadium com- served cerebrovascular disturbances remain cal. Considering the fact, that spontaneous of the obhypotheti- course of acute vanadate poisoning in man is still unknown, it should be emphasized, that no distinct cause-and-effect relationship can be claimed for the detoxification treatment applied. 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