ABSTRACT
El metotrexato es un fármaco análogo del ácido fólico ampliamente utilizado en el tratamiento de enfermedades autoinmunes, leucemias y linfomas. Su uso puede ocasionar la aparición de múltiples efectos adversos entre los que se encuentran aquellos relacionados con la presencia de toxicidad neurológica, que puede presentarse de forma aguda, subaguda o crónica. La neurotoxicidad subaguda es aquella que ocurre típicamente entre los 2 y los 14 días posteriores a la administración y puede manifestarse con una amplia gama de síntomas neurológicos. En la mayoría de los casos, no recurre con futuras exposiciones al medicamento. Presentamos tres casos de neurotoxicidad subaguda por metotrexato con manifestaciones clínicas diferentes en pacientes oncohematológicos que se internaron entre los años 2018 y 2020. Dos de ellos presentaron recurrencia frente a la nueva administración del fármaco y todos evidenciaron lesiones en resonancia magnética nuclear.
Methotrexate is a folic acid analogue widely used in the treatment of autoimmune diseases, leukemias, and lymphomas. Methotrexate use may cause multiple adverse effects, including those related to the presence of neurological toxicity, which may be acute, subacute, or chronic. Subacute neurotoxicity typically occurs between 2 and 14 days after administration and may present as a wide range of neurological symptoms. In most cases, it does not recur with future exposures to the drug. Here we describe 3 cases of subacute methotrexate neurotoxicity with different clinical manifestations in patients with oncohematological disease who were hospitalized between 2018 and 2020. Two of them showed recurrence with a new drug administration. Lesions were observed in the magnetic resonance imaging tests of all of them.
Subject(s)
Humans , Male , Child , Adolescent , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/pathology , Neurotoxicity Syndromes/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Lymphoma , Magnetic Resonance Imaging , Methotrexate/adverse effects , Antimetabolites, Antineoplastic/adverse effectsABSTRACT
La neurotoxicidad de la isoniazida (INH) frecuentemente no es tenida en cuenta por el pediatra ante un paciente con un cuadro convulsivo agudo. La INH es uno de los fármacos más indicados en el tratamiento y quimioprofilaxis de la tuberculosis. Habitualmente se la indica al grupo familiar, debido a las características epidemiológicas de esta enfermedad, lo cual permite una amplia disponibilidad en los hogares, pudiendo originar intoxicaciones accidentales o intencionales. La intoxicación severa se caracteriza por un cuadro neurotóxico agudo, expresado en un síndrome convulsivo o coma, que no cede con el tratamiento habitual. Se presenta un caso clínico de una paciente intoxicada grave con isoniazida, habiendo sido la anamnesis dirigida ampliada junto con un diagnóstico precoz y el tratamiento específico con el antídoto, la base fundamental para la evolución favorable de la paciente.
Pediatricians do not usually considered isoniazid (INH) neurotoxicity in cases of patients with severe seizure disorders. INH is one of the most suitable drugs in the treatment and chemoprophylaxis of tuberculosis. It is usually indicated to the family group, due to the epidemiological characteristics of this disease, allowing a wide availability in homes and being able to cause accidental or intentional poisoning. An acute neurotoxic picture, expressed as a convulsive syndrome or coma, which does not improve with the usual treatments, characterized severe intoxication. A case of a patient with severe intoxication with isoniazid is presented. The extended anamnesis, along with an early diagnosis and the specific antidote treatment, set the fundamental basis for the favorable evolution of the patient.
Subject(s)
Humans , Female , Adolescent , Isoniazid/toxicity , Pyridoxine/administration & dosage , Neurotoxicity Syndromes/drug therapy , Seizures/diagnosisABSTRACT
BACKGROUND: Paclitaxel, an anti-neoplastic agent effective against several solid tumors, has several side effects including peripheral neuropathy. So far, there are no effective treatments for this complication. Monosialic acid ganglioside (GM1) has been shown to protect neurons against injuries and degeneration. However, its efficacy in the treatment of paclitaxel-induced neuropathy has not been verified. OBJECTIVE: To evaluate the effect of porcine GM1 on neurophysiological abnormalities in rats receiving paclitaxel. MATERIAL AND METHOD: Fifty-four Wistar rats were divided into control, vehicle for paclitaxel (Cremophor EL), paclitaxel, and paclitaxel + GM1 groups. Paclitaxel 16 mg/kg/week for five consecutive weeks was given intraperitoneally. Treatment with 30 mg/kg 5 days per week of GM1 was started 3 days prior to the first dose and continued until 3 days after the last dose of paclitaxel. Tail and hind paw thermal thresholds including tail motor nerve conduction velocity (MNCV) were measured prior to and after the start of treatments. Histopathology of the sciatic nerve was also examined. RESULTS: Paclitaxel alone induced thermal hypoalgesia and reduced tail MNCV Less severe abnormalities were also found with the vehicle. GM1 appeared to prevent the development of hypoalgesia and ameliorated the decreased MNCV without any evidence of Guillain-Barre Syndrome. Mild endoneurial edema and axonal degeneration in the sciatic nerve sections were seen in paclitaxel treated rats. Microtubule accumulation and activated Schwann cell were also presented in the paclitaxel treated groups. CONCLUSION: These data suggest that porcine GM1 may be useful in the prevention and treatment of paclitaxel-induced neuropathy. However the adverse effect of Cremophor EL should be of concern.
Subject(s)
Animals , Antineoplastic Agents, Phytogenic/toxicity , Dose-Response Relationship, Drug , G(M1) Ganglioside/adverse effects , Neurotoxicity Syndromes/drug therapy , Paclitaxel/toxicity , Peripheral Nervous System Diseases/chemically induced , Rats , Rats, Wistar , Sensation/drug effectsABSTRACT
Acute poisoning by organophosphorus (OP) compounds is a major global clinical problem, with thousands of deaths occurring every year. Most of these pesticide poisoning and subsequent deaths occur in developing countries following a deliberate self ingestion of the poison. Metacid (Methyl parathion) and Nuvan (Dichlorovos) are commonly ingested OP pesticides; Dimethoate, Profenofos, and Chlorpyrifos are other less frequently ingested compounds in Nepal. The toxicity of these OP pesticides is due to the irreversible inhibition of acetylcholinesterase (AChE) enzyme leading to accumulation of acetylcholine and subsequent over-activation of cholinergic receptors in various parts of the body. Acutely, these patients present with cholinergic crisis; intermediate syndrome and delayed polyneuropathy are other sequel of this form of poisoning. The diagnosis depends on the history of exposure to these pesticides, characteristic manifestations of toxicity and improvements of the signs and symptoms after administration of atropine. The supportive treatment of OP poisoning includes the same basic principles of management of any acutely poisoned patient i.e., rapid initial management of airways, breathing, and circulation. Gastric lavage and activated charcoal are routinely used decontamination procedures, but their value has not been conclusively proven in this poisoning. Atropine is the mainstay of therapy, and can reverse the life threatening features of this acute poisoning. However, there are no clear cut guidelines on the dose and duration of atropine therapy in OP poisoning. Cholinesterase reactivators, by regenerating AChE, can reverse both the nicotinic and muscarinic effects; however, this benefit has not been translated well in clinical trials. All these facts highlight that there are many unanswered questions and controversies in the management of OP poisoning and there is an urgent need for research on this aspect of this common and deadly poisoning.
Subject(s)
Antidotes/therapeutic use , Decontamination/methods , Humans , Incidence , Neurotoxicity Syndromes/drug therapy , Organophosphorus Compounds/poisoning , Global HealthABSTRACT
Isoniazid is an effective and widely used drug in tuberculosis treatment. The administration of toxic amounts of INH causes recurrent seizures, profound metabolic acidosis, coma and even death but therapeutic dose of isoniazid is a very rare cause of seizures. We present a case of 44-year-old HIV positive African-American female who was recently started on a preventive dose of INH after being found purified protein derivative (PPD) positive. She developed status-epilepticus that did not respond to most of the antiepileptics. As soon as she received intravenous pyridoxine, the seizures terminated abruptly.