Metronidazole-induced Neurotoxicity Research Articles

Metronidazole-induced neurotoxicity: Possible central serotonergic and noradrenergic system involvement

Background: Metronidazole is a synthetic 5-nitroimidazole antibiotic. It remains a first-line therapy for anaerobic, parasitic, and bacterial infections in human and veterinary medicine. However, Metronidazole-induced neurotoxicity is a rising challenge. The mechanism of neurotoxicity induction is still unknown. Objective: To investigate a possible interference of metronidazole with central monoaminergic mechanisms using the Forced Swim Test. Methods: sixty adult rats were divided into 10 groups (n=10 for metronidazole and saline, n=5 for other groups). Group 1 = 5 ml/kg normal saline; Group 2 = 50 mg/kg metronidazole; group 3= 15 mg/kg imipramine; Group 4 =15 mg/kg imipramine + 50 mg/kg metronidazole. Group 5 = 5 mg/kg fluoxetine; Group 6 received 5 mg/kg fluoxetine + 50 mg/kg metronidazole; Group 7 = labetalol 10 mg/kg; Groups 8, 9 and 10 received labetalol 10 mg/kg + 50 mg/kg metronidazole, PCPA (p-chlorophenylalanine) 100 mg/kg and PCPA 100 mg/kg + 50 mg/kg metronidazole daily X 28 days. On day 28, FST was done 1h after the respective treatments. On day 29, blood samples were collected under halothane anesthesia for hematological assessment. Results: Immobility time increased (P<0.01) in the groups treated with metronidazole, labetalol, PCPA, labetalol + metronidazole, and PCPA+ metronidazole. Swimming was reduced by metronidazole, PCPA, metronidazole + PCPA and metronidazole + labetalol. Metronidazole + labetalol reduced climbing. These effects were not reduced by co-treatment with imipramine or fluoxetine. White blood cell count increased (p<0.01) in all treatment groups. Lymphocyte percent increased in the metronidazole-treated groups. Conclusion: Interference with postsynaptic central monoaminergic neurotransmission and immunomodulation may contribute to metronidazole-induced neurotoxicity.

Mechanistic Assessment of Anise Seeds and Clove Buds against the Neurotoxicity Caused by Metronidazole in Rats: Possible Role of Antioxidants, Neurotransmitters, and Cytokines.

Long-term use of the nitroimidazole-derived antibiotic metronidazole has been associated with neuronal damage due to its ability to cross the blood-brain barrier. Polyphenol-rich plants, such as anise seeds and clove buds, are suggested to have neuroprotective effects. However, their intracellular protective pathway against metronidazole-induced neurotoxicity remains unexplored. This study aims to evaluate the potential neuroprotective benefits of anise seeds and clove buds and elucidate the proposed metronidazole-induced neurotoxicity mechanism. This study divided rats into six groups, each containing six rats. In Group I, the control group, rats were administered saline orally. Group II rats received 200 mg/kg of metronidazole orally. Group III rats received 250 mg/kg b.w. of anise seed extract and metronidazole. Group IV rats received 500 mg/kg b.w. of anise seed extract (administered orally) and metronidazole. Group V rats received 250 mg/kg b.w. of clove bud extract (administered orally) and metronidazole. Group VI rats were administered 500 mg/kg b.w. of clove bud extract and metronidazole daily for 30 consecutive days. The study evaluated the phenolic compounds of anise seeds and clove buds. Moreover, it assessed the inflammatory and antioxidant indicators and neurotransmitter activity in brain tissues. A histological examination of the brain tissues was conducted to identify neuronal degeneration, brain antioxidants, and apoptotic mRNA expression. The study found that metronidazole treatment significantly altered antioxidant levels, inflammatory mediators, and structural changes in brain tissue. Metronidazole also induced apoptosis in brain tissue and escalated the levels of inflammatory cytokines. Oral administration of metronidazole resulted in a decrease in GABA, dopamine, and serotonin and an increase in ACHE in brain tissue. Conversely, oral administration of anise and clove extracts mitigated the harmful effects of metronidazole. The neurotoxic effects of metronidazole appear to stem from its ability to reduce antioxidants in brain tissue and increase nitric oxide production and apoptosis. The study concludes that neuronal damage caused by metronidazole is significantly mitigated by treatment with anise and clove extracts.

Metronidazole-induced neurotoxicity

Rationale: Nervous system toxicity is a rare complication of metronidazole. Prompt identification of metronidazole toxicity combined with a comprehensive physical rehabilitation program is essential to maximizing the patient’s functional outcome. Patient concerns: A 58-year-old female was treated with metronidazole for embolic versus hematogenous spread of bacteria resulting in multifocal brain abscesses. Two weeks after discharge, the patient returned to the emergency department with slurred speech, muscle aches, generalized weakness, inability to ambulate, and poor oral intake. Diagnosis: Head magnetic resonance imaging revealed symmetric enhanced T2/FLAIR signaling in the dentate nuclei were also present bilaterally, a finding pathognomonic for metronidazole toxicity. Intervention: Metronidazole was discontinued, and the patient was enrolled in a comprehensive rehabilitation program. Outcomes: She began inpatient rehabilitation dependent for all activities of daily living and requiring moderate assistance for transfers. She could only walk 10 feet with a front-wheeled walker with a 2-person assist. The patient rapidly improved with a comprehensive rehabilitation program, and due to these improvements, she was discharged after 5 days of inpatient rehabilitation. At the time of discharge, she was independent with all activities of daily living and could walk 160 feet independently with a front-wheeled walker. Lessons: Prompt recognition and discontinuation of metronidazole remains the only known effective treatment. A comprehensive approach to treatment and rehabilitation is achieved with an early referral to rehabilitation services. This is crucial to minimize morbidity and optimize functional outcomes in this patient population.

Metronidazole-induced Neurotoxicity: A Case Report

Metronidazole-induced Neurotoxicity: A Case Report

Metronidazole-induced neurotoxicity.

Metronidazole, usually prescribed for anaerobic and protozoal infections, can uncommonly cause adverse effects involving the central nervous system. The exact mechanism is unclear. In 1 case–control study, the incidence of neurologic events was 0.25%, although this is likely an underestimate.[1][1

Long-term Implication of Metronidazole Induced Reversible Cerebellar Toxicity and Peripheral Neuropathy- A Case Report

Metronidazole Induced Encephalopathy (MIE) is rare and serious central nervous system toxicity. A 40-year-old male, on long-term self treatment with metronidazole (cumulative dose: 102 gm) presented with dysarthria, nystagmus, unsteadiness, and numbness in both legs. A Magnetic Resonance Imaging (MRI) scan of the brain revealed a symmetric hyperintensity in both the dentate nuclei of cerebellum on both T2 weighted and Fluid-Attenuated Inversion-Recovery (FLAIR) imaging. Discontinuation of metronidazole resulted in resolution of the imaging findings and clinical improvement occurred within one month. Metronidazole-induced neurotoxicity should be considered in patient who present with cerebellar symptoms and characteristic lesion on MRI in close temporal relation with metronidazole intake and drug should be discontinued to prevent permanent neurological deficit.

Long-term Implication of Metronidazole Induced Reversible Cerebellar Toxicity and Peripheral Neuropathy- A Case Report

Metronidazole Induced Encephalopathy (MIE) is rare and serious central nervous system toxicity. A 40-year-old male, on long-term self treatment with metronidazole (cumulative dose: 102 gm) presented with dysarthria, nystagmus, unsteadiness, and numbness in both legs. A Magnetic Resonance Imaging (MRI) scan of the brain revealed a symmetric hyperintensity in both the dentate nuclei of cerebellum on both T2 weighted and Fluid-Attenuated Inversion-Recovery (FLAIR) imaging. Discontinuation of metronidazole resulted in resolution of the imaging findings and clinical improvement occurred within one month. Metronidazole-induced neurotoxicity should be considered in patient who present with cerebellar symptoms and characteristic lesion on MRI in close temporal relation with metronidazole intake and drug should be discontinued to prevent permanent neurological deficit.

Acute metronidazole-induced neurotoxicity: an update on MRI findings

To describe a series of 10 cases of metronidazole-induced neurotoxicity (MIN) and review the established literature to better define its clinical and imaging findings. The clinical presentations and magnetic resonance imaging (MRI) images of 10 patients with clinically diagnosed MIN were reviewed retrospectively. A review of an additional 31 cases from prior published case series was performed. The median age of patients from the authors' institutions with MIN was 54 (range 8-84) years. The median cumulative dose of metronidazole received was 64.5 g (range 7.5-1,380 g). Common presenting neurological symptoms were ataxia (n=6) and altered mental status (n=3). All of the patients (n=10) had symmetric T2 hyperintense lesions in the dentate nuclei at presentation. Other involved structures included the midbrain, corpus callosum, pons, medulla, basal ganglia, and supratentorial white matter. True restricted diffusion was seen in the corpus callosum (n=6). Symptoms resolved in all patients except for one. For the patients with available follow up MRI (n=4), the observed lesions resolved. MIN affects both adult and paediatric patients. Symptoms typically occur after prolonged exposure to the antibiotic, but can occur at low cumulative doses. Most frequently involved structures are the dentate nucleus, midbrain, and splenium corpus callosum. Restricted diffusion within the corpus callosum is likely due to cytotoxic oedema. Symptoms typically resolve after cessation of metronidazole, and lesions typically resolve on follow-up imaging.

Sequential MR imaging (with diffusion-weighted imaging) changes in metronidazole-induced encephalopathy.

Metronidazole-induced neuro-toxicity, though rare, is known. A characteristic spatial distribution of lesions in cerebellar dentate nuclei and dorsal pons is known. However, temporal progression of lesions on magnetic resonance imaging (MRI) has not been described previously. We describe two such cases which presented initially with splenial hyperintesity and showed progression to characterstic lesions. Both cases improved with stoppage of metronidazole.

Predominant Jaw Myoclonus from Cefepime Toxicity: A Case Report and a Review of the Literature.

Predominant Jaw Myoclonus from Cefepime Toxicity: A Case Report and a Review of the Literature.

Neurologic Complications of Metronidazole

Metronidazole (Flagyl®) is an antimicrobial agent commonly used in clinical practice. Although it is generally well tolerated with minimal side effects, there are a host of still under-recognized neurologic complications of metronidazole treatment. The following review is aimed at summarizing current literature pertaining to metronidazole-induced neurotoxicity including clinical syndromes, neuroradiological findings, prognosis and proposed pathophysiology. Recognition of the neurotoxic effects of metronidazole is critical as prompt discontinuation is generally associated with full clinical recovery and radiological resolution.

Metronidazole Toxicity: A Case Series (P04.159)

Objective: To describe four new cases of metronidazole toxicity. To correlate clinical findings with radiologic diagnoses of patients who presented with neurotoxicity as a direct result of their exposure to metronidazole. To review the characteristic MRI findings of metronidazole-induced neurotoxicity in order to aid in diagnosis of this potentially reversible condition. Background Metronidazole is a medication used frequently for treatment of infections caused by anaerobic bacteria and protozoa in multiple organ systems. With extended use, metronidazole can lead to neurotoxicity. There have been few reports in the literature demonstrating the classical MRI findings associated with metronidazole-induced cerebellar toxicity and the reversal of both clinical symptoms and imaging findings with cessation of the medication. Design/Methods: Retrospective case series. Results: We will review the pathophysiology of metronidazole-induced toxicity and present four novel cases of metronidazole-induced cerebellar toxicity with corresponding MR imaging. Conclusions: Patients with metronidazole-induced neurotoxicity present with bilateral cerebellar findings, correlating to abnormal signal in bilateral dentate nuclei. Bilateral dentate nuclei demonstrate hyperintensity on T2-weighted MR images, with increased DWI and ADC signal in metronidazole-induced neurotoxicity. In addition to resolution of clinical symptoms, the imaging findings reverse with cessation of metronidazole treatment. Correlation of clinical presentation with classic MRI findings can lead to more rapid and accurate diagnosis of this potentially reversible condition. Disclosure: Dr. Reaven has nothing to disclose. Dr. Reaven has nothing to disclose. Dr. Kouo has nothing to disclose. Dr. Shin has nothing to disclose.

Metronidazole-Induced Neurotoxicity Developed in Liver Cirrhosis

A 68 year-old-male with hepatitis C-positive liver cirrhosis was admitted because of liver abscess. After metronidazole was initiated against the infection, mental disturbance appeared. Hepatic encephalopathy was suspected at first, however, the brain MRI showed hyperintense lesion of the bilateral basal dendric nuclei which indicated metronidazole-associated encephalopathy. The symptoms became well after cessation of the drug. Metronidazole is a widely used medicine against various infections. Recent case reports describe that this medicine can induce reversible encephalopathy. However, there have been few reports regarding metronidazole-induced encephalopathy occurred in patients with cirrhosis. Here we report on a case of hepatic cirrhosis and abscess in which reversible metronidazole-induced encephalopathy developed.

A mechanism for metronidazole-induced neurotoxicity

A mechanism for metronidazole-induced neurotoxicity