RESUMEN
Metronidazole can cause adverse effects both in the central and peripheral nervous system. We report a 34-year-old female who presented a reversible cerebellar syndrome and peripheral neuropathy as an adverse effect associated with the use of metronidazole. Brain magnetic resonance imaging (MRI) showed hyperintense T2 and FLAIR bilateral symmetrical cerebellar lesions, without contrast enhancement or mass effect, isointense in diffusion-weighted imaging and hypointense in apparent diffusion coefficient sequences. Also, electrophysiological evaluation was consistent with axonal polyneuropathy. She had received metronidazole for a liver abscess during 49 days. After discontinuation of metronidazole, she had rapid regression of cerebellar symptoms and normalization of MRI, with subsequent disappearance of peripheral symptoms. The brain MRI, electromyography and nerve conduction studies performed at 35 months later showed complete resolution of the lesions. Although metronidazole neurotoxicity is a rare event, it must be borne in mind because the prognosis is usually favorable after stopping the drug.
Asunto(s)
Antiprotozoarios/efectos adversos , Enfermedades Cerebelosas/inducido químicamente , Metronidazol/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Adulto , Femenino , Humanos , Absceso Hepático/tratamiento farmacológico , Imagen por Resonancia MagnéticaRESUMEN
Metronidazole can cause adverse effects both in the central and peripheral nervous system. We report a 34-year-old female who presented a reversible cerebellar syndrome and peripheral neuropathy as an adverse effect associated with the use of metronidazole. Brain magnetic resonance imaging (MRI) showed hyperintense T2 and FLAIR bilateral symmetrical cerebellar lesions, without contrast enhancement or mass effect, isointense in diffusion-weighted imaging and hypointense in apparent diffusion coefficient sequences. Also, electrophysiological evaluation was consistent with axonal polyneuropathy. She had received metronidazole for a liver abscess during 49 days. After discontinuation of metronidazole, she had rapid regression of cerebellar symptoms and normalization of MRI, with subsequent disappearance of peripheral symptoms. The brain MRI, electromyography and nerve conduction studies performed at 35 months later showed complete resolution of the lesions. Although metronidazole neurotoxicity is a rare event, it must be borne in mind because the prognosis is usually favorable after stopping the drug.
Asunto(s)
Adulto , Femenino , Humanos , Antiprotozoarios/efectos adversos , Enfermedades Cerebelosas/inducido químicamente , Metronidazol/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Absceso Hepático/tratamiento farmacológico , Imagen por Resonancia MagnéticaRESUMEN
The present work reports cerebellar degeneration in cattle associated with the ingestion of Solanum subinerme in northern Brazil. The main clinical signs were periodic crises with loss of balance, falls, opisthotonus, and nystagmus. The histological lesions consisted of diffuse vacuolation of the perikaryon of the Purkinje neurons, followed by the loss of these cells and their substitution by Bergman glia. It is concluded that S. subinerme is another species of Solanum that causes cerebellar degeneration in cattle.
Asunto(s)
Enfermedades de los Bovinos/patología , Corteza Cerebelosa/patología , Enfermedades Cerebelosas/inducido químicamente , Enfermedades Cerebelosas/veterinaria , Enfermedades Neurodegenerativas/inducido químicamente , Enfermedades Neurodegenerativas/veterinaria , Intoxicación por Plantas/patología , Intoxicación por Plantas/veterinaria , Solanum/toxicidad , Animales , Conducta Animal , Brasil , Bovinos , Enfermedades Cerebelosas/patología , Femenino , Masculino , Enfermedades Neurodegenerativas/patología , Células de Purkinje/patologíaRESUMEN
PURPOSE: Phenytoin is known to be able to induce cerebellar atrophy in patients with epilepsy. It is also known that a CYP2C9 mutation (*2 or *3) reduces phenytoin metabolism by 25-50% and can increase the risk of phenytoin-related side effects. We examined the influence of CYP2C9 polymorphisms on total cerebellar volume and cerebellar gray and white matter volumes in patients with epilepsy taking phenytoin. METHODS: For the genotyping, 100 adult patients with documented epilepsy who had been taking phenytoin for >1 year were selected. From this group, we randomly selected 19 mutant individuals (MT group; CYP2C9*2 and *3) for a whole-brain volume measurement using MRI and 19 wild-type individuals (group WT; CYP2C9*1) with similar clinical and demographic characteristics to those in the MT group for comparison. Total intracranial volume measurements were used to normalize the acquired volumes, which were separated into gray matter volume, white matter volume, and total volume. RESULTS: The MT group exhibited a significant reduction in cerebellar white matter volume (p=0.002) but not in total cerebellar volume. CONCLUSION: Our study is the first to report evidence linking CYP2C9 polymorphism and a reduction in cerebellar volume in epileptic users of phenytoin.
Asunto(s)
Anticonvulsivantes/efectos adversos , Hidrocarburo de Aril Hidroxilasas/genética , Atrofia/genética , Enfermedades Cerebelosas/genética , Epilepsia/genética , Fenitoína/efectos adversos , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Anciano , Alelos , Anticonvulsivantes/uso terapéutico , Atrofia/inducido químicamente , Enfermedades Cerebelosas/inducido químicamente , Citocromo P-450 CYP2C9 , Epilepsia/tratamiento farmacológico , Femenino , Interacción Gen-Ambiente , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenitoína/uso terapéuticoRESUMEN
Heme oxygenase (HO) catalyses the breakdown of heme to iron, carbon monoxide and biliverdin, the latter being further reduced to bilirubin. A protective role of the inducible isoform, HO-1, has been described in pathological conditions associated with the production of reactive oxygen species (ROS). The aim of this study was to investigate the role of HO-1 in the neurotoxicity induced by iodoacetate (IAA) in primary cultures of cerebellar granule neurons (CGNs). IAA, an inhibitor of the glycolysis pathway, reduces cell survival, increases ROS production and enhances HO-1 expression in CGNs. Furthermore, the induction of HO-1 expression by cobalt protoporphyrin (CoPP) prevented cell death and ROS production induced by IAA, whereas the inhibition of HO activity with tin mesoporphyrin exacerbated the IAA-induced neurotoxicity. The protective effect elicited by CoPP was reproduced by bilirubin addition, suggesting that this molecule may be involved in the protective effect of HO-1 induction in this experimental model.
Asunto(s)
Bilirrubina/farmacología , Cerebelo/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Ácido Yodoacético/toxicidad , Neuronas/efectos de los fármacos , Neuronas/enzimología , Animales , Bilirrubina/metabolismo , Western Blotting , Enfermedades Cerebelosas/inducido químicamente , Enfermedades Cerebelosas/enzimología , Enfermedades Cerebelosas/prevención & control , Cerebelo/citología , Cerebelo/enzimología , Inducción Enzimática , Hemo-Oxigenasa 1/antagonistas & inhibidores , Hemo-Oxigenasa 1/biosíntesis , Metaloporfirinas/farmacología , Neuronas/metabolismo , Protoporfirinas/farmacología , Ratas , Ratas Endogámicas BB , Especies Reactivas de Oxígeno/metabolismo , Tubulina (Proteína)/metabolismoRESUMEN
In this article, we report the case history of a 44-year-old female patient with bipolar disorder who developed the so-called Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT). A detailed description of our patient's neurologic status is provided at baseline (i.e. during lithium intoxication) and after one year of follow-up, confirming the persistency of cerebellar signs and symptoms. Although rare, our report - which shows a severe and disabling form of SILENT - underscores the need to perform a strict control of the putative risk factors argued to be associated with the development of this syndrome. In our case, the presence of fever and the administration of multiple doses of antipsychotics may have contributed to the poor outcome exhibited by the patient.
Asunto(s)
Antimaníacos/efectos adversos , Trastorno Bipolar/tratamiento farmacológico , Enfermedades Cerebelosas/inducido químicamente , Compuestos de Litio/efectos adversos , Síndromes de Neurotoxicidad/etiología , Adulto , Femenino , HumanosAsunto(s)
Antimaníacos/envenenamiento , Encéfalo/patología , Enfermedades Cerebelosas/inducido químicamente , Carbonato de Litio/envenenamiento , Adulto , Ataxia/inducido químicamente , Atrofia , Trastorno Bipolar/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Enfermedades Cerebelosas/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Convulsiones/inducido químicamenteAsunto(s)
Adulto , Femenino , Humanos , Antimaníacos/envenenamiento , Encéfalo/patología , Enfermedades Cerebelosas/inducido químicamente , Carbonato de Litio/envenenamiento , Atrofia , Ataxia/inducido químicamente , Trastorno Bipolar/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Enfermedades Cerebelosas/patología , Imagen por Resonancia Magnética , Convulsiones/inducido químicamenteRESUMEN
Chelating therapy has been reported as a useful approach for counteracting mercurial toxicity. Moreover, 2,3-dimercapto-1-propanesulfonic acid (DMPS), a tissue-permeable metal chelator, was found to increase urinary mercury excretion and decrease mercury content in rat brain after methylmercury (MeHg) exposure. We evaluated the capability of DMPS to reduce MeHg-induced motor impairment and cerebellar toxicity in adult mice. Animals were exposed to MeHg (40 mg/L in drinking water, ad libitum) during 17 days. In the last 3 days of exposure (days 15-17), animals received DMPS injections (150 mg/kg, i.p.; once a day) in order to reverse MeHg-induced neurotoxicity. Twenty-four hours after the last injection (day 18), behavioral tests related to the motor function (open field and rotarod tasks) and biochemical analyses on oxidative stress-related parameters (cerebellar glutathione, protein thiol and malondyaldehyde levels, glutathione peroxidase and glutathione reductase activities) were carried out. Histological analyses for quantifying cellular damage and mercury deposition in the cerebellum were also performed. MeHg exposure induced a significant motor deficit, observed as decreased locomotor activity in the open field and decreased falling latency in the rotarod apparatus. DMPS treatment displayed an ameliorative effect toward such behavioral parameters. Cerebellar glutathione and protein thiol levels were not changed by MeHg or DMPS treatment. Conversely, the levels of cerebellar thiobarbituric acid reactive substances (TBARS), a marker for lipid peroxidation, were increased in MeHg-exposed mice and DMPS administration minimized such phenomenon. Cerebellar glutathione peroxidase activity was decreased in the MeHg-exposed animals, but DMPS treatment did not prevent such event. Histological analyses showed a reduced number of cerebellar Purkinje cells in MeHg-treated mice and this phenomenon was completely reversed by DMPS treatment. A marked mercury deposition in the cerebellar cortex was observed in MeHg-exposed animals (granular layer>Purkinje cells>molecular layer) and DMPS treatment displayed a significant ameliorative effect toward these phenomena. These findings indicate that DMPS displays beneficial effects on reversing MeHg-induced motor deficits and cerebellar damage in mice. Histological analyses indicate that these phenomena are related to its capability of removing mercury from cerebellar cortex.
Asunto(s)
Enfermedades Cerebelosas/prevención & control , Compuestos de Metilmercurio/toxicidad , Trastornos de la Destreza Motora/prevención & control , Unitiol/farmacología , Análisis de Varianza , Animales , Antídotos/administración & dosificación , Antídotos/farmacología , Antídotos/uso terapéutico , Conducta Animal/efectos de los fármacos , Enfermedades Cerebelosas/inducido químicamente , Enfermedades Cerebelosas/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Inyecciones Intraperitoneales , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Trastornos de la Destreza Motora/inducido químicamente , Trastornos de la Destreza Motora/fisiopatología , Células de Purkinje/efectos de los fármacos , Células de Purkinje/metabolismo , Células de Purkinje/patología , Compuestos de Sulfhidrilo/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Factores de Tiempo , Unitiol/administración & dosificación , Unitiol/uso terapéuticoRESUMEN
Cerebellar morphogenesis as well as somatometric parameters of progenies from mothers exposed to ethyl-ether, chloroform, turpentine or thinner were registered a 24, 48 and 7 hours of age. 1. Mortality rate of 20 and 59% was observed in progenies of thinner or turpentine exposed mothers, correspondingly. 2. Delay of intrauterine growth manifested by body weight, size and cephalic diameter was evident in chloroform exposed groups (P < 0.01). 3. Cerebellar maturation delay was found in thinner or turpentine prenatally exposed litters. 4. The number of Purkinje cells was significantly reduced in ethyl-ether and chloroform exposed groups (P < 0.01). These cells were found less affected by thinner or turpentine exposure (P < 0.01).
Asunto(s)
Anomalías Inducidas por Medicamentos/etiología , Enfermedades Cerebelosas/inducido químicamente , Retardo del Crecimiento Fetal/inducido químicamente , Preñez/efectos de los fármacos , Solventes/toxicidad , Administración por Inhalación , Animales , Animales Recién Nacidos , Cefalometría , Enfermedades Cerebelosas/embriología , Enfermedades Cerebelosas/patología , Cloroformo/administración & dosificación , Cloroformo/toxicidad , Éter/administración & dosificación , Éter/toxicidad , Femenino , Masculino , Intercambio Materno-Fetal , Vehículos Farmacéuticos/administración & dosificación , Vehículos Farmacéuticos/toxicidad , Embarazo , Células de Purkinje/efectos de los fármacos , Células de Purkinje/patología , Ratas , Ratas Sprague-Dawley/embriología , Solventes/administración & dosificación , Trementina/administración & dosificación , Trementina/toxicidadRESUMEN
En el presente trabajo se realiza una puesta al día de la Encefalopatía o Demencia Dialítica (ED) trastorno neurológico de gran interés, eminentemente asociado a la hemodiálisis crónica. Se revisan las diversas etiologías implicadas, destacando en particular la toxicidad por aluminio como causa de mayor relevancia a la luz de la información actual. Se describe el cuadro clínico en extensión, con sus variadas manifestaciones semiológicas, su evolución, los estudios complementarios de mayor utilidad en su diagnóstico, los hallazgos neuropatológicos, los variados diagnósticos diferenciales, así como las medidas profilácticas y terapéuticas pertinentes. Además, se establecen algunos alcances con patologías asociadas tanto a la ED como a la toxicidad por aluminio. Finalmente se presentan 6 casos clínicos documentados estudiados por el autor, con especial énfasis en su expresión clínica, su evolución, los hallazgos del laboratorio, las terapias aplicadas y su relación con elevadas concentraciones de alumninio en la solución de diálisis como en el suero de los pacientes