Cerebellar syndrome caused by metronidazole Translated title: Síndrome cerebeloso secundario a metronidazol

The clinical manifestations of antibiotic-induced neurotoxic effects, the underlying mechanisms and management strategies have been reviewed. PubMed and OVID searches (January 1960-June 2010) were conducted using search terms such as antibiotics, side effects, neurotoxicity and encephalopathy which yielded approximately 300 articles. All relevant case reports, case series, letters and retrospective reviews describing neurotoxic effects and those discussing mechanisms of neurotoxicity were included. Antibiotic-induced neurotoxic side effects can have a myriad of neurologic presentations. Patients with prior central nervous system (CNS) disease, renal insufficiency and advanced age may be particularly vulnerable. Treatment consists of discontinuation of the offending agent, use of antiepileptic drugs in the case of seizures or status epilepticus and haemodialysis in certain cases. The risk of CNS toxicity may be reduced via dosage adjustments in high risk populations. Awareness of the potential neurotoxic clinical manifestations of various antibiotics and high degree of vigilance in critically ill patients is essential in identifying a potentially serious, though reversible complications of antibiotic therapy particularly with the advent of newer antimicrobial agents. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

MR imaging features of metronidazole-induced encephalopathy (MIE) have not been fully established. This study was undertaken to determine the topographic distributions and diffusion-weighted imaging (DWI) findings of MIE. We retrospectively evaluated the initial MR images (n = 7), including DWI (n = 5), and follow-up MR images (n = 4) after drug discontinuation in 7 patents with clinically diagnosed MIE. The topographic distributions of lesions were evaluated on MR images, and DWI signal intensities and apparent diffusion coefficient (ADC) values of the lesions were assessed. MR images demonstrated bilateral symmetric T2 hyperintense lesions in the cerebellar dentate nucleus (n = 7), midbrain (n = 7), dorsal pons (n = 6), medulla (n = 4), corpus callosum (n = 4), and cerebral white matter (n = 1). Brain stem lesions involved the following: tectum (n = 5), tegmentum (n = 4), red nucleus (n = 3) of the midbrain, vestibular nucleus (n = 6), and a focal tegmental lesion involving the superior olivary nucleus (n = 6) and abducens nucleus (n = 4) of the pons and vestibular nucleus (n = 4) and inferior olivary nucleus (n = 1) of the medulla. DWI (n = 5) showed isointensity or hyperintensity of lesions, and the decreased ADC value was found only in the corpus callosum lesions (n = 2). All detected lesions were completely reversible at follow-up except for the single corpus callosum lesion with an initial low ADC value. Brain lesions were typically located at the cerebellar dentate nucleus, midbrain, dorsal pons, medulla, and splenium of the corpus callosum. According to DWI, most of the lesions in MIE probably corresponded to areas of vasogenic edema, whereas only some of them, located in the corpus callosum, corresponded to cytotoxic edema.

Sir, I read with interest the articles by Gupta et al and Gulati et al on adverse drug reactions of antituberculous drugs.[1 2] I would like to make the following comments. Adverse drug reactions (ADRs) are a major cause of morbidity, hospital admission, and even death. Hence it is essential to recognise ADRs and to establish a causal relationship between the drug and the adverse event. It is desirable that ADRs should be objectively assessed and presented based on an acceptable “Probability Scale.” Many causality methods have been proposed to assess the relationship between a drug and an adverse event in a given patient, ranging from short questionnaires to comprehensive algorithms. The idea of creating a standardized assessment for the relationship-likelihood of case reports of suspected ADRs was in the hope that this would, in a structured way, lead to a reliable reproducible measurement of causality. The causality assessment system proposed by the World Health Organization Collaborating Centre for International Drug Monitoring, the Uppsala Monitoring Centre (WHO–UMC), and the Naranjo Probability Scale are the generally accepted and most widely used methods for causality assessment in clinical practice as they offer a simple methodology.[3 4] The above scales are structured, transparent, consistent, and easy to apply assessment methods. Table 1 summarizes the “Naranjo ADR Probability Scale,” which has gained popularity among clinicians because of its simplicity.[3] The WHO–UMC causality system takes into account the clinical-pharmacologic aspects, whereas previous knowledge of the ADR plays a less prominent role. Table 2 summarizes the WHO–UMC Probability Scale.[4] Table 1 Naranjo ADR probability scale—items and score Question Yes No Don’t know Are there previous conclusion reports on this reaction? +1 0 0 Did the adverse event appear after the suspect drug was administered? +2 –1 0 Did the AR improve when the drug was discontinued or a specific antagonist was administered? +1 0 0 Did the AR reappear when drug was re-administered? +2 –1 0 Are there alternate causes [other than the drug] that could solely have caused the reaction? –1 +2 0 Did the reaction reappear when a placebo was given? –1 +1 0 Was the drug detected in the blood [or other fluids] in a concentration known to be toxic? +1 0 0 Was the reaction more severe when the dose was increased or less severe when the dose was decreased? +1 0 0 Did the patient have a similar reaction to the same or similar drugs in any previous exposure? +1 0 0 Was the adverse event confirmed by objective evidence? +1 0 0 Scoring for Naranjo algorithm: >9 = definite ADR; 5–8 = probable ADR; 1–4 = possible ADR; 0 = doubtful ADR. Table 2 WHO–UMC causality categories Causality term Assessment criteria (all points should be reasonably complied) Certain Event or laboratory test abnormality, with plausible time relationship to drug intake Cannot be explained by disease or other drugs Response to withdrawal plausible (pharmacologically, pathologically) Event definitive pharmacologically or phenomenologically (ie, an objective and specific medical disorder or a recognized pharmacologic phenomenon) Rechallenge satisfactory, if necessary Probable/likely Event or laboratory test abnormality, with reasonable time relationship to drug intake Unlikely to be attributed to disease or other drugs Response to withdrawal clinically reasonable Rechallenge not required Possible Event or laboratory test abnormality, with reasonable time relationship to drug intake Could also be explained by disease or other drugs Information on drug withdrawal may be lacking or unclear Unlikely Event or laboratory test abnormality, with a time to drug intake that makes a relationship improbable (but not impossible) Disease or other drugs provide plausible explanation Conditional/unclassified Event or laboratory test abnormality More data for proper assessment needed, or Additional data under examination Unassessable/unclassifiable Report suggesting an adverse reaction Cannot be judged because information is insufficient or contradictory Data cannot be supplemented or verified I humbly request the Editors that Lung India should use either of the above two scales while reviewing articles related to ADRs.