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Table of Contents    
CASE REPORT
Year : 2021  |  Volume : 69  |  Issue : 1  |  Page : 174-176

Metronidazole-Induced Recurrent Paresthesia: A Case Report


Department of Physical Medicine and Rehabilitation, Kyung-Hee Medical Center, 23, Kyungheedae-ro, Dongdaemun-gu, Seoul, Korea

Date of Submission12-Jun-2018
Date of Decision07-Apr-2020
Date of Acceptance05-Jun-2020
Date of Web Publication24-Feb-2021

Correspondence Address:
Yunsoo Soh
Department of Physical Medicine and Rehabilitation, Kyung-Hee Medical Center, 23, Kyungheedae-ro, Dongdaemun-gu, Seoul
Korea
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.310097

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 » Abstract 


A 54-year-old woman presented with a 1-month history of pain and numbness in both feet. She had taken metronidazole for over 4 years previously to treat vaginitis. On nerve conduction studies (NCS), neither the sural nor right superficial peroneal nerve (SPN) was evoked, nor did the left SPN have small amplitude, suggesting axonal peripheral polyneuropathy with sensory fiber involvement. When she restarted metronidazole, she immediately complained of recurrent paresthesia of the feet. We performed three electromyography (EMG) studies and followed the patient for 6 months.


Keywords: Electromyography, metronidazole, nerve conduction studies, peripheral neuropathy,
Key Message: Metronidazole can cause recurrent peripheral neuropathy and should be used with caution, particularly during prolonged and large doses. We report the patient with metronidazole-induced recurrent peripheral neuropathy confirmed by three times EMG studies.


How to cite this article:
Soh Y. Metronidazole-Induced Recurrent Paresthesia: A Case Report. Neurol India 2021;69:174-6

How to cite this URL:
Soh Y. Metronidazole-Induced Recurrent Paresthesia: A Case Report. Neurol India [serial online] 2021 [cited 2021 Apr 11];69:174-6. Available from: https://www.neurologyindia.com/text.asp?2021/69/1/174/310097




Metronidazole is a 5-nitroimidazole derivative with potent activity against anaerobic bacteria, and it is also used to treat protozoa infections, including Trichomonas, Entamoeba, and Giardia, and Escherichia coli, Helicobacter pylori, and Guinea worm (Dracunculus medinensis). Trichomonas vaginitis can be treated with metronidazole for many years without causing major adverse drug reactions. The major adverse reactions are generally tolerable and include nausea, abdominal discomfort, dizziness, diarrhea, and a metallic taste in the mouth. Serious, less common, side-effects include pseudomembranous colitis, seizures, ataxia, and central neurotoxicity.[1],[2],[3],[4] Peripheral polyneuropathy is an uncommon side effect. Electromyography (EMG) is the most informative part of the electrodiagnostic evaluation and commonly includes both needle EMG and nerve conduction studies (NCS).[5] For needle EMG, it is necessary to insert thin needles into the muscles. NCS delivers a small electric shock, and the electric signals are detected via small electrodes attached to the skin. Due to its objectivity, reliability, and sensitivity in the measurement of peripheral nerve function, EMG has long been a standard tool for confirming peripheral neuropathies.[6] We report a patient who developed peripheral polyneuropathy confirmed with an EMG study following the prolonged intake of metronidazole. Three EMG studies were performed and the patient was followed for six months.


 » Case Report Top


A 54-year-old woman presented with a 1-month history of pain and paresthesia in both feet. Her symptoms were aggravated when she stepped on the floor. At her first visit, the visual analog scale (VAS) score of the paresthesia was 9. There was no pallor or hyperpigmentation of her skin. She had no history of hypertension, diabetes, or tuberculosis medication. Her surgical history comprised a hysterectomy for a large uterine myoma ten years previously and oophorectomy and salpingectomy for pelvic inflammatory disease 3 years ago. She had taken metronidazole 500 mg twice daily for more than a year, four years earlier, to treat vaginitis. There was sensory disturbance but no definite motor weakness or vascular claudication. The deep tendon reflexes were normal. We investigated the patient's familial history, blood tests including thyroid function test, toxic or drug exposure history except metronidazole to investigate other possible polyneuropathy causes but no remarkable findings. Lumbar spine magnetic resonance imaging (MRI) performed to rule out radiculopathy but only mild bulging of the lumbosacral discs observed without compression of the nerve root. We performed three electromyography (EMG) studies when she visited with paresthesia. At the first nerve conduction study (NCS), the motor NCS was normal, but in the sensory NCS neither the sural nor the right superficial peroneal nerve (SPN) were evoked, and the left SPN showed small amplitude. The F wave showed slightly delayed latency at the left common peroneal nerve, and the H reflex was normal. Needle EMG showed no abnormal spontaneous activity and normal motor unit action potentials. These findings suggested axonal peripheral polyneuropathy with sensory fiber involvement [Table 1].
Table 1: The results of the initial sensory nerve conduction study

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After excluding other causes of polyneuropathy, we diagnosed metronidazole-induced peripheral neuropathy. She was asked to stop taking metronidazole. One month later, her symptoms had improved to VAS 2. Two months later, she visited a gynecologist at a local clinic because of vaginal itching and was prescribed metronidazole again. Within four days, she complained of paresthesia of the feet and her VAS score for the paresthesia had worsened to 5. To evaluate her symptoms, a follow-up NCS was done. In this study, the sural and right SPN was not evoked. The sensory NCS findings had worsened when she restarted oral metronidazole. Although the paresthesia had improved, she experienced immediate paresthesia associated with the resumption of metronidazole [Table 2].
Table 2: The results of the follow.up sensory nerve conduction study done after 4 days of metronidazole intake

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A third NCS was done six months after the first EMG study. Her paresthesia had improved and the VAS score was two. Although the sensory NCS study showed decreased amplitudes at both the sural nerve and right SPN, both nerves were evoked, showing improved axonal polyneuropathy compared with the previous NCS studies [Table 3].
Table 3: The results of the last follow up sensory nerve conduction study, done 6 months after the first NCS study

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 » Discussion Top


Metronidazole-induced peripheral neuropathy is a complication of prolonged treatment with high doses of metronidazole. The peripheral neuropathy is typically characterized by numbness, paresthesia, and neuropathic pain in the distal limbs. Patients may also have decreased reflexes, muscle weakness or atrophy, and abnormal nerve conduction in NCS. EMG is the most useful test for determining the localization, pathophysiology (axonal or demyelinating), acuity, and severity of peripheral neuropathies.[6] Some studies have used NCS to evaluate the peripheral neuropathy caused by metronidazole. Duffy et al. performed NCS on 13 pediatric Crohn's disease patients on long-term metronidazole and found that 11 of the patients had findings consistent with peripheral neuropathy.[7] Kapoor et al. performed NCS on 17 patients and found that the NCS results for the peripheral nerves of the lower limbs changed significantly after three weeks of treatment.[8] Peripheral neuropathy can be divided into neuropathy that primarily affects axons or the myelin sheath. Axon loss may be seen after toxin exposure.[6] In animal experiments, Bradley et al. found that metronidazole and its metabolic product could bind to RNA and inhibit protein synthesis, resulting in axonal denervation in nerve fibers.[3] In our case, the paresthesias were somewhat correlated with the amplitude of the sensory NCS. These findings imply that metronidazole has a role in axonal denervation. In conclusion, we report an unusual case of recurrent paresthesia associated with the intake of metronidazole. The patient experienced immediate paresthesia when she restarted metronidazole, and we performed three EMG studies over six months. In a systemic review of metronidazole-induced peripheral neuropathy, Goolsby et al. suggested that peripheral neuropathy is best expressed in terms of the total dose in grams.[9] Metronidazole should be used with caution and clear indications, particularly during prolonged courses and when prescribed in large doses. We suggest that a careful neurological examination and EMG study should be performed in patients who complain of symptoms of peripheral neuropathy during treatment with metronidazole.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Gupta B, Baldwa S, Verma S, Gupta J, Singhal A. Metronidazole induced neuropathy. Neurol India 2000;48:192-3.  Back to cited text no. 1
[PUBMED]  [Full text]  
2.
Andersson K. Pharmacokinetics of nitroimidazoles. Spectrum of adverse reactions. Scandinavian journal of infectious diseases Supplementum 1981;26:60-7.  Back to cited text no. 2
    
3.
Bradley W, Karlsson I, Rassol C. Metronidazole neuropathy. Br Med J 1977;2:610-1.  Back to cited text no. 3
    
4.
Ferris DG, Litaker MS, Woodward L, Mathis D, Hendrich J. Treatment of bacterial vaginosis: A comparison of oral metronidazole, metronidazole vaginal gel, and clindamycin vaginal cream. J Fam Pract 1995;41:443-50.  Back to cited text no. 4
    
5.
Yang Z, Zhang Y, Chen R, Huang Y, Ji L, Sun F, et al. Simple tests to screen for diabetic peripheral ne?uropathy. Cochrane Database Syst Rev. 2018 Jul; 2018 (7): CD010975.  Back to cited text no. 5
    
6.
Chung T, Prasad K, Lloyd TE. Peripheral neuropathy–Clinical and electrophysiological considerations. Neuroimaging Clin N Am 2014;24:49-65.  Back to cited text no. 6
    
7.
Duffy LF, Daum F, Fisher SE, Selman J, Vishnubhakat SM, Aiges HW, et al. Peripheral neuropathy in Crohn's disease patients treated with metronidazole. Gastroenterology 1985;88:681-4.  Back to cited text no. 7
    
8.
Kapoor K, Chandra M, Nag D, Paliwal J, Gupta R, Saxena R. Evaluation of metronidazole toxicity: A prospective study. Int J Clin Pharmacol Res 1998;19:83-8.  Back to cited text no. 8
    
9.
Goolsby TA, Jakeman B, Gaynes RP. Clinical relevance of metronidazole and peripheral neuropathy: A systematic review of the literature. Int J Antimicrob Agents 2018;51:319-25.  Back to cited text no. 9
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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