Catatonia in disulfiram intoxication - a case report and a brief overview of the literature.

Catatonic syndromes could accompany a variety of psychiatric and medical conditions. The most common conditions underlying catatonia are affective disorders followed by schizophrenia, but several medical conditions including intoxications affecting the central nervous system can also present with catatonic signs and symptoms. Therapeutic doses of disulfiram could induce catatonia with or without accompanying psychosis or mood disorder. A case of disulfiram intoxication manifesting with catatonia is reported here together with a brief overview of the literature. A patient was admitted to the toxicology ward after a suicide attempt with approximately 20 g of disulfiram. On transfer to the psychiatric ward, she was sitting still, in a semi-stuporous state and displayed motiveless resistance to instructions or attempts to move (active negativism). She was unresponsive to most of the questions (mutism), occasionally verbigerated 1-2 words and stared for more than 20 seconds between shifting attention. After developing a comatosus state her treatment continued at the toxicology ward, where a contrast-enhanced computer tomography scan revealed bilateral emollition of 1.5 cm diameter in both nucleus lentiformis at the level of the third ventricle. Following treatment her condition improved and she benefited of rehabilitation facility and a second psychiatric treatment. She was discharged free of neurological and psychiatric symptoms. In conclusion, we underscore the importance of accurate diagnosis of the underlying psychiatric or medical condition when encountering a fast emerging catatonic syndrome and focus first on treating the causative condition while simultaneously attempting symptomatic treatment of catatonia.

A case of Wernicke encephalopathy combined with disulfiram intoxication.

There have been several reports of disulfiram intoxication, but little evidence of neurologic conditions resulting from disulfiram-induced brain damage combined with Wernicke encephalopathy-associated lesions. We report a rare patient with both Wernicke encephalopathy and disulfiram intoxication. This 50-year-old woman, who was taking disulfiram for chronic alcohol abuse, presented with an acute confusional state, dysarthria, nystagmus, supranuclear ophthalmoplegia, and paraparesis. Biochemical serum and cerebrospinal fluid analyses were normal. An electromyogram detected a motor polyneuropathy. Cognitive assessment revealed severe impairment of memory, attention, and logical and executive abilities. Magnetic resonance imaging with gadolinium enhancement showed brain lesions consistent with Wernicke encephalopathy, but also symmetric hyperintensities on T2-weighted images in the globus pallidus. Stopping the disulfiram and treating with hydration, high-dose thiamine supplements, and benzodiazepines significantly improved the patient's consciousness and oculomotor function. A magnetic resonance imaging scan after 1 month of treatment showed complete disappearance of the brain lesions and the hyperintensities in the globus pallidus. After a further month of intensive neurorehabilitation, the patient was able to interact with the medical staff, and her neuropsychological tests showed only mild memory impairment. Patients with alcoholism who present at emergency departments are at high risk for misdiagnosis, especially because there is no specific routine laboratory test for detecting asymptomatic disulfiram intoxication. Although uncommon, the combination of Wernicke encephalopathy and disulfiram intoxication should be suspected in patients with alcoholism. The disorder can be detected through a careful history and prompt clinical evaluation, together with characteristic magnetic resonance imaging findings.

Disulfiram ethanol reaction mimicking anaphylactic, cardiogenic, and septic shock.

Shock is a common reason for medical intensive care unit admission, with septic and cardiogenic accounting for most of the etiologies. However, the potential severity of adverse side effects of drugs indicates that any medication should be carefully scrutinized for potential pharmacokinetic and pharmacodynamic interactions that may result. We herein report the case of a life-threatening shock mimicking successively anaphylactic, cardiogenic, and septic shock, which was finally related to disulfiram ethanol reaction. Indeed, disulfiram ethanol reaction is known to provoke unpleasant symptoms through vasodilatation in various organs. However, extreme manifestations of vasodilatory shock may lead to circulatory failure and lactic acidosis. Because of large prevalence of alcoholism and disulfiram medication, emergency physicians and medical specialists should be aware of this life-threatening condition, with its misleading presentation.

Delayed and prolonged coma after acute disulfiram overdose.

We report the case of a 35-year-old man presenting with a delayed and prolonged coma due to an intentional overdose with disulfiram without simultaneous alcohol ingestion. The clinical features--comprising a severe toxic encephalopathy with coma and convulsions, in combination with a quadriparesis outlasting the loss of consciousness--are summarized, and the physiopathology is reviewed.

Cardiogenic shock caused by disulfiram.

Drug intoxication with disulfiram is a rare condition that may lead to severe and potentially fatal cardiovascular manifestations such as cardiogenic shock. We report the case of a female patient with refractory shock after deliberate self-poisoning with disulfiram. Clinical, biochemical and echocardiographic assessment, as well as invasive monitoring confirmed cardiogenic shock associated with this drug. The known mechanisms of action of disulfiram are discussed, and the major collateral effects, especially cardiovascular effects, are described. We underscore the importance of suspecting this diagnosis and of adopting prompt and the most adequate therapeutic approach in this context.

Choque cardiogênico por dissulfiram / Cardiogenic shock caused by disulfiram / Shockcardiogénico por disulfiram

A intoxicação medicamentosa por dissulfiram é uma situação rara, mas, que pode se apresentar com manifestações cardiovasculares graves e potencialmente fatais, como choque cardiogênico. É apresentado o caso de uma paciente com choque refratário, após intoxicação voluntária por dissulfiram. A avaliação clínica e bioquímica, junto à avaliação ecocardiográfica e à monitorização invasiva, confirmaram tratar-se de um choque cardiogênico associado a esse fármaco. São discutidos os mecanismos de ação conhecidos do dissulfiram e descritos os principais efeitos colaterais, especialmente os cardiovasculares, alertando para a importância da suspeição diagnóstica e da abordagem terapêutica imediata mais adequada nesse contexto.

Drug intoxication with disulfiram is a rare condition that may lead to severe and potentially fatal cardiovascular manifestations such as cardiogenic shock. We report the case of a female patient with refractory shock after deliberate self-poisoning with disulfiram. Clinical, biochemical and echocardiographic assessment, as well as invasive monitoring confirmed cardiogenic shock associated with this drug. The known mechanisms of action of disulfiram are discussed, and the major collateral effects, especially cardiovascular effects, are described. We underscore the importance of suspecting this diagnosis and of adopting prompt and the most adequate therapeutic approach in this context.

La intoxicación medicamentosa por disulfiram es una situación rara, aunque puede presentarse con manifestaciones cardiovasculares graves y potencialmente fatales, como el shock cardiogénico. Este relato presenta el caso de una paciente con shock refractario, tras intoxicación voluntaria por disulfiram. La evaluación clínica y bioquímica, junto a la evaluación ecocardiográfica y el monitoreo invasivo, confirmaron tratarse de un shock cardiogénico asociado a ese fármaco. A lo largo del presente relato se discuten los mecanismos de acción del disulfiram conocidos, así como se describen los principales efectos colaterales, específicamente los cardiovasculares. En este sentido, también se alerta para la importancia de la sospecha diagnóstica y del abordaje terapéutico inmediato más adecuado a este contexto.

Acute vocal fold palsy after acute disulfiram intoxication.

Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.

[Wernicke's encephalopathy associated with chronic disulfiram intoxication]. / Encéphalopathie de Gayet-Wernicke associée a une intoxication chronique au disulfiram.

INTRODUCTION: We report the case of a patient with an unusual association of Wernicke encephalopathy and chronic disulfiram intoxication. CASE REPORT: A 41-year-old man presented with progressive frontal decline and akineto-rigid parkinsonism under chronic disulfiram therapy. He also developed acute confusion with ataxia, blepharospasm, and supranuclear ophthalmoplegia following a severe malnutrition due to refusal of food intake. Brain MRI revealed symmetrical and reversible hyperintense lesions on T2 and FLAIR in the posterior putaminal regions, dorso-medial thalamic and subthalamic nuclei, the periaqueducal gray matter, the cerebellar peduncles, and the pontine tegmentum. A slow partial clinical recovery with persistent frontal syndrome was observed after discontinuation of disulfiram and parenteral administration of thiamine. DISCUSSION: The symmetry and reversibility of the MRI lesions in the basal ganglia and brain stem were suggestive of a deficiency, a toxic or a metabolic neurological disease. The dorso-medial thalamo-subthalamic and brainstem localizations, as well as their occurrence in a state of malnutrition, were consistent with Wernicke encephalopathy. Moreover, chronic disulfiram intoxication might explain the frontal syndrome and the akineto-rigid parkinsonism, associated with MRI putaminal lesions. Similar MRI lesions have been described in the so-called "energy deprivation syndromes", which are toxic, genetic or nutritional disorders that disrupt enzymes involved in energy generating metabolic pathways such as glycolysis and pyruvate oxidation.

Mycotoxins revisited: Part II.

Mushrooms are ubiquitous in nature. They are an important source of nutrition, however, certain varieties contain chemicals that can be highly toxic to humans. Industrially cultivated mushrooms are historically very safe, whereas foraging for mushrooms or accidental ingestion of mushrooms in the environment can result in serious illness and death. The emergency department is the most common site of presentation for patients suffering from acute mushroom poisoning. Although recognition can be facilitated by identification of a characteristic toxidrome, the presenting manifestations can be variable and have considerable overlap with more common and generally benign clinical syndromes. The goal of this two-part article is to review the knowledge base on this subject and provide information that will assist the clinician in the early consideration, diagnosis and treatment of mushroom poisoning. Part I reviewed the epidemiology and demographics of mushroom poisoning, the physical characteristics of the most toxic varieties, the classification of the toxic species, and presented an overview of the cyclopeptide-containing mushroom class. Part II is focused on the presentation of the other classes of toxic mushrooms along with an up-to-date review of the most recently identified poisonous varieties.

[Imaging in acute toxic encephalopathy]. / Imagerie des encephalopathies toxiques aigues.

Neuroimaging, particularly MR imaging, plays a major role for the diagnosis of many acute toxic encephalopathies. Toxic disorders are related to drugs (immunosuppressive agents, chemotherapeutic agents, anti-epileptic drugs, heroin...), to metals (lead, manganese, mercury...), and to industrial and environmental chemicals (solvent, carbon monoxide...). MR imaging with diffusion and perfusion imaging provides information regarding brain lesions induced by the toxic agents (vasogenic edema, cytotoxic edema, infarction, hemorrhage, demyelination...).

Systemic hemodynamic effects of treatment with the molecular adsorbents recirculating system in patients with hyperacute liver failure: a prospective controlled trial.

The aim of the study is to evaluate the effect of a single treatment with the molecular adsorbents recirculating system (MARS) on systemic hemodynamics and oxygen consumption (VO(2)) in patients with hyperacute liver failure (HALF). In a controlled design, eight patients with HALF were assigned to a 6-hour MARS treatment, and five patients, to a control group that was mechanically cooled to match the MARS group. Systemic hemodynamic variables were determined hourly during the study period. In the MARS group, systemic vascular resistance index increased by 46% from 1,215 +/- 437 to 1,778 +/- 710 dynes x s x cm(-5) x m(-2) (P <.0001), which significantly exceeded a 6% increase in the control group. Mean arterial pressure increased from 69 +/- 5 to 83 +/- 11 mm Hg in the MARS group (P <.0001) and was unchanged in the control group. Cardiac index decreased by 20% from 4.6 +/- 1.8 to 3.7 +/- 1.1 L/min x m(-2) (P =.0007) in the MARS group and by 7% in the control group. Heart rate decreased from 105 +/- 21 to 85 +/- 15 beats/min in the MARS group (P <.0001) and was unchanged in the control group. In the MARS group, oxygen delivery decreased from 621 +/- 198 to 486 +/- 141 mL/min x m(-2) (P <.05), and VO2, from 142 +/- 31 to 112 +/-21 mL/min x m(-2) (P <.05). Arterial lactate and pH levels were unchanged. In conclusion, systemic hemodynamic values tend to normalize, whereas systemic VO(2) decreases during MARS treatment in patients with HALF. These effects cannot be explained by the degree of cooling associated with MARS.

[Acute disulfiram intoxication with severe neurological sequaelae and presenting misleading psychiatric deficiency]. / Intoxication aiguë au disulfirame avec séquelles neurologiques graves et présentation psychiatrique déficitaire trompeuse.

Disulfiram self poisoning is exceptional. The authors report on the case of such an intoxication related to the ingestion of a potentially lethal dose of this drug (30 g) and draw the attention on the following points: 1) The initial signs may be misleading because they include both psychiatrics and neurological signs such as phonation abnormalities, myoclonias and tetraparesia. 2) The evolution is unforseeable with the possible occurrence of severe psychological and motricity sequaelae, associated with bilateral and symetric injuries of the putamen, the palladium and the basal nuclei on CT-scan (or MRI). The pathophysiologic al mechanisms of theses signs are discussed, and the need for disulfiram in the care of alcoholic patients seeking for withdrawal as well.

[Suicidal self poisoning with disulfiram in a 15-year old boy with resulting encephalopathy]. / Samobójcze ostre zatrucie disulfiramem u 15-letniego chlopca z nastepowa encefalopatia.

Acute intentional overdoses of disulfiram (app. 30 g) is reported in 15-years-old boy. The neurological disturbances as nystagmus, coma, seizures and than impairment of memory and perception were dominated in the clinical picture. During MRI examination the areas of different signal from corpus callosum were detected which can be referred to focus of demyelinisation. The patient recovered and was discharged from the hospital after 30 days. Neuropsychological examinations have suggested dysfunction of CNS. The control MRI examination 90 days later, did not reveal any pathological changes in the brain.

Differential mechanisms in the effects of disulfiram and diethyldithiocarbamate intoxication on striatal release and vesicular transport of glutamate.

Intoxication with the alcohol-aversive drug disulfiram (Antabuse) and related dithiocarbamates may provoke neuropathies and, in some cases, damage the basal ganglia. Rats received a single administration of disulfiram (7 and 500 mg kg-1 i.p.) and equimolar doses (4 and 290 mg kg-1 i.p.) of its metabolite diethyldithiocarbamate (DDC), roughly corresponding to the daily maximum dose in alcohol abusers or to an estimated nonlethal overdose, respectively. The striatal, extracellular levels of glutamate in freely moving rats previously implanted with a microdialysis probe increased after low and intoxicating doses of disulfiram (126 +/- 3% and 154 +/- 10% of basal values, respectively) and DDC as well (135 +/- 10% and 215 +/- 14%, respectively), a partially Ca++-dependent effect. The prolonged (>7 hr) disulfiram-induced increase in glutamate observed in vivo may reflect the in vitro disulfiram-evoked release of glutamate from striato-cortical synaptic vesicles, where the drug nonspecifically inhibited (Ki approximately 4 microM) the uptake function and abolished the transmembrane proton gradient (DeltapH). In contrast, DDC did not seem to affect DeltapH. The prompt DDC-provoked increase in extracellular levels of glutamate was prevented by 7-nitroindazole, an in vivo specific inhibitor of neuronal nitric oxide synthase, which suggests that the thiol metabolite also acts via the nitric oxide synthesis. At variance, the short-acting 7-nitroindazole did not prevent the sustained in vivo effects of disulfiram and of DDC putatively formed with time. These findings provide new evidence for differential mechanisms underlying disulfiram- and DDC-induced increases in striatal glutamate release. Present glutamatergic changes, although not appearing dramatic enough to represent the only cause for neuronal damage from disulfiram overdose, might contribute to the drug neurotoxicity.