Why Would Methodrozole Treatment Mwke Me Ffel Well for a Couple Days Then Hurt Again After Taking It
CMAJ. 2009 Oct 27; 181(ix): 611–613.
Reversible cerebellar syndrome caused by metronidazole
Patient 1
A 54-year-old man presented with a iii-24-hour interval history of difficulty speaking and an unsteady gait after having a generalized tonic-clonic seizure. He had been taking oral metronidazole for bronchiectasis for 2 months earlier presentation (estimated cumulative dose of about 60 thou). His medical history included recently diagnosed type 2 diabetes mellitus and dyslipidemia. He had no family history of neurologic disorders.
Neurological examination showed cerebellar dysarthria, bilateral dysmetria and an ataxic broad-based gait. The rest of the test was unremarkable. The results of magnetic resonance imaging (MRI) of the patient's encephalon were reported to be normal, although, in hindsight, faint hyperintensities within the dentate nuclei could be seen on the T 2-weighted fluid-attenuated inversion recovery (FLAIR) scans. The patient's symptoms and signs improved over the adjacent four days.
One week later, the patient's dysarthria and ataxia (gait and appendicular) worsened, and he was admitted to hospital. Echo T 2-weighted FLAIR MRI showed obvious bilateral symmetric hyperintensities inside the dentate nuclei of the cerebellum (Effigy 1A). The results of a thorough work-up for cerebellar disorders were negative: nutritional causes (vitamin B12 and vitamin E deficiencies) and genetic disorders (Friedreich clutter, spinocerebellar ataxias 1, 2, 3, 6, seven and 8, cerebrotendinous xanthomatosis) were ruled out. About 1 month later on access, phenytoin was initiated after a second seizure.
Axial magnetic resonance images of the first patient's brain while taking metronidazole (A) and afterward discontinuation of metronidazole (B), and of the second patient's encephalon while on metronidazole (C) and after disconntinuation of metronidazole (D). Cerebellar dentate hyperintensities (arrowheads) on fluid-attenuated inversion recovery imaging are visible for both patients while taking metronidazole (A, C), which resolved after the drug was stopped (B, D).
At the initial presentation, the cause of the patient's difficulties was not recognized, and he connected to take metronidazole for bronchiectasis until this therapy was discontinued about 2 months later on. At a follow-upward examination 3 months subsequently discontinuation of metronidazole, the patient's cerebellar syndrome had resolved. A repeat MRI scan of the patient'south brain showed complete resolution of signal changes within the dentate nuclei (Figure 1B).
Patient 2
A 72-year-sometime woman was admitted with pain in her left leg and flank from an intra-intestinal abscess. Her medical history included coronary avenue affliction with a remote myocardial infarction and subsequent coronary artery featherbed graft surgery. Her history also included hypothyroidism, a left nephrectomy for a renal abscess and a remote history of smoking.
About 3 weeks afterwards initiation of metronidazole (500 mg twice a day, cumulative dose of well-nigh 25 one thousand), she developed a cerebellar syndrome with cerebellar dysarthria, dysmetria and gait ataxia. An MRI scan of her brain taken nearly 2 months after the onset of this syndrome showed aberrant betoken within the cerebellar dentate nuclei bilaterally on T 2-weighted FLAIR imaging (Figure 1C), which was virtually identical to the findings for patient 1. Based on these findings, metronidazole toxicity was suspected, and the drug was discontinued. The patient'southward symptoms gradually resolved over the next few weeks. An MRI scan of her brain taken 1 calendar month after metronidazole was stopped showed complete resolution of the cerebellar dentate lesions (Figure 1D). The patient died ii months later of unrelated causes.
Discussion
Metronidazole is an antibody widely used in clinical exercise, only example reports1 – 4 take shown that both peripheral and central nervous organization–associated neurotoxicity tin can occur with metronidazole utilise (Box 1). Peripheral neuropathy is the virtually common agin neurologic effect caused past metronidazole. Most of the adverse effects are reversible within weeks of discontinuation of treatment.
A reversible cerebellar syndrome with characteristic cerebellar dentate nuclei lesions on T 2-weighted FLAIR MRI scans has been attributed to metronidazole use, equally described for our 2 patients and by others.4 – seven Patients usually present with cerebellar dysarthria and ataxia that may occasionally fluctuate, every bit in our start patient. The duration of treatment with metronidazole before cerebellar symptoms manifest is variable, ranging from 28 days6 to 3 months,7 and cumulative doses range from 25 k (as in our 2d patient) to 90 1000.seven Patients ordinarily experience complete resolution of the symptoms later discontinuation of metronidazole, sometimes inside a few days. To our knowledge, there accept been no published reports of cerebellar syndrome associated with metronidazole that take not improved after discontinuation of metronidazole therapy. Our patients' symptoms and signs resolved within weeks of stopping metronidazole. The MRI changes also resolved in both patients, thereby implicating the drug as the causative agent.
The reversible cerebellar syndrome described by us and by others is correlated with striking and symmetric MRI T two–FLAIR hyperintensities inside the dentate nuclei of the cerebellum. Other areas of the brain may too be affected by metronidazole use, including the midbrain, pons, medulla, corpus callosum and other brainstem regions.8 The cerebellar dentate nuclei is the about normally affected area.
The mechanism of action of metronidazole-induced neurotoxicity on the central and peripheral nervous systems is not well understood. Proposed mechanisms include bounden of metronidazole to RNA, DNA and inhibitory neurotransmitters, besides every bit inducing both vasogenic and cytotoxic edema.6 Metronidazole is structurally similar to the thiazole precursor of thiamine and could thereby lead to a reduction in thiamine absorption by acting as a thiamine analog.nine
The propensity to develop these agin effects is poorly understood. In that location may be some relation to dose, but in both of our patients, the administered dose was within the recommended range. Patient 2 developed the syndrome later a relatively depression cumulative dose of just 25 grand, which is at the low cease of the range of doses associated with cerebellar syndrome. Synergistic toxicity with other medications is also possible.x
The neurotoxic adverse furnishings of metronidazole go along to be underrecognized despite its widespread use. Our recognition of the cause for the dentate lesions in our get-go patient was delayed until one of us (S.F.) came across a example description in a specialty journal. Recognition of the syndrome prompted discontinuation of metronidazole for patient two.
Adverse side effects from medications, particularly when unexpected and serious, should be reported to the Canada Vigilance Programme (www.healthcanada.gc.ca/medeffect).
Footnotes
This article has been peer reviewed.
Previously published at world wide web.cmaj.ca
Competing interests: None declared.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764756/
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