CASE PRESENTATION

1. CASE PRESENTATION DR. GAURAV KHATANA MAULANA AZAD MEDICAL COLLEGE

2. Patient X, 45 years/Male resident of UP presented to the Medicine Emergency with Chief Complaints of: • Tingling and numbness in all four limbs for 10 days • Difficulty in walking for 3 days • Slurring of speech for 2 days

3. HISTORY OF PRESENT ILLNESS • Tingling and numbness- insidious in onset, gradually progressive limited to glove and stocking distribution In distal part of all four limbs, no weakness. • Difficulty in walking - insidious in onset, gradually progressive swaying while standing and walking , no history of falls walk with adjustment of gait without any support was not exacerbated in dark abnormal body or head movements. • Slurring of speech - slow with multiple pauses no difficulty in understanding or following commands.

4. PAST HISTORY : Patient was suffering from fever, recurrent vomiting, RUQ 2month back for which he visited local doctor. An USG abdomen was done of which the report is not available but patient had been prescribed tablet metronidazole 800 mg twice daily which he was still continuing till presentation. Patient was afebrile for last 2 weeks. • No h/o tuberculosis diabetes, hypertension. • No h/o any other long term drug intake apart from metronidazole. • PERSONAL HISTORY : Non smoker, Alcoholic for 5 years, moderate amount 3 to 4 times a month, No history of high risk behavior. • FAMILY HISTORY : No significant family history.

5. No H/O : • diminution in vision, diplopia. • headache, vomiting, loss of consciousness, seizure episode. • deviation of mouth, nasal regurgitation of food, nasal intonation of voice. • hearing difficulty or tinnitus. • jaundice, abdominal distension • bladder bowel incontinence, burning micturition. • rash, swelling , back pain, arthralgia. • anorexia and significant weight loss. • similar episode in past.

6. GENERAL PHYSICAL EXAMINATION • Conscious, oriented and cooperative. • BP : 130/90 mmHg Pulse : 84/min • Temp : 98.2 • Pallor -ve Icterus −ve • Cyanosis −ve Edema −ve • Clubbing −ve Lymphadenopathy −ve • JVP - NR • PE −ve • No rash, skin/nail changes. • Thyroid -NAD • No stigmata of chronic liver disease.

7. SYSTEMIC EXAMINATION CNS EXAMINATION • Higher functions/ Cranial nerve examination/ Motor functions -WNL • Sensory system : pain and temp sensation diminished in B/L lower limb below ankle. Sensations ,Vibration, proprioception and joint position- WNL Romberg's sign - negative. • Cerebellar signs: Intention tremors – present. Finger nose test – positive for dysmetria and past pointing bilaterally Disdiadochokinesia– present bilaterally Heel knee test - positive bilaterally. • Reflexes: B/L ankle jerk absent rest all other DTR – WNL, B/L Plantar – flexor. • Gait - Broad based with B/L swaying, Tandem walking - impaired

8. ACUTE ONSET SENSORY POLYNEUROPATHY WITH CEREBELLAR ATAXIA • Alcohol induced neurotoxicity. • Viral infection with viral cerebellitis • Drug (? Metronidazole) induced neurotoxicity. • Posterior circulation stroke • Malignancy with paraneoplastic syndrome.

9. INVESTIGATIONS :

10. USG ABDOMEN : • Liver: shows two heterogenoushypoechoic lesion Right lobe of liver, largest meas. 90 cc in seg vii with liquefied contents. • Urine R/M : WNL • Peripheral Smear : WNL • Chest X Ray : WNL • ECG : WNL • NCCT HEAD: WNL • HIV/HBsAg/Anti HCV- NR. • CSF: no cells, sugar 72, protein 61 • Amoebic serology: positive • Vit B12 levels : 377 pg /ml. Serum AFP - normal.

11. CECT ABDOMEN: Two hypodense lesion in right lobe of liver with liquefied content, without any contrast enhancement. s/o liver abscess. NCV test: S/O bilateral axonal sensory neuropathy. MRI BRAIN:

15. MRI BRAIN : • Areas of confluent T2/ FLAIR W hyper intensities shows restriction over DW images involving the dentate nuclei and body and splenium of corpus callosum ( BOOMERANG SIGN) not associated with any significant mass effect. S/o encephalitis- ? Drug induced ? viral etiology. • Differential Diagnosis : - Acute infectious encephalitis (influenza, mumps, adenovirus, EBV and rotavirus) • Osmotic myelinosis • Maple Syrup Urine Disease • Drug induced (methyl bromide intoxication, methotrexate,5- fluorouracil ).

16. Final diagnosis– Metronidazole induced cerebellar toxicity and peripheral neuropathy.

17. Further clinical course: • Within 10 days of stopping of metronidzole, patient started improving. • 2- 3 weeks later showed complete clinical improvement with no cerebellar signs or symptoms of peripheral neuropathy. • Repeat MRI brain and NCV are planned.

18. REVIEW OF LITERATURE: • Metronidazole is a 5-nitroimidazole compound , exerts its antimicrobial effects through the production of free radicals that are toxic to the microbes & is used to treat Aspiration pneumonias, intra-abdominal abcess, pseudomembranous colitis, amoebiasis and other anaerobic infections. • Common adverse drug reactions are nausea, diarrhea, weight loss, abdominal pain, vomiting, headache, dizziness, and metallic taste in the mouth. • High doses and long-term systemic treatment s/e are leucopenia, neutropenia, peripheral neuropathy, and central nervous system toxicity. Neurotoxicity – • It produces various neurologic features such as seizure, peripheral neuropathy, autonomic neuropathy, optic neuropathy ,cerebellar syndrome, encephalopathy.

19. DOSE : In a study by Kim et al. the duration of treatment with metronidazole before cerebellar symptoms manifest is variable, and cumulative doses range from 25 g to 110 g. (Journal of Medical Case Reports 2011) • DURATION: Most of the reported patients with metronidazole induced encephalopathy presented within 1-12 weeks following metronidazole exposure and the imaging abnormalities resolve between 3 and 16 weeks after stopping metronidazole. (Neurol India 2011;59:4-5) • Although the CNS toxicity is not perfectly dose and duration related, metronidazole induced peripheral neuropathy is dose related. Generally it occurs after 10-14 days of high dose metronidazole therapy and it is axonal sensorimotor neuropathy. (Gupta B S.Neurol India 2000;48:192)

20. Magnetic resonance imaging (MRI) abnormalities have been described with metronidazole overdosage; however, it is not clear why only few patients develop these abnormalities and also with serum levels in the therapeutic range. • MRI brain lesions are hyperintense on T-2 with no mass effect. Characteristically, these lesions are mostly symmetric and bilateral involving cerebellar dentate nuclei, midbrain, dorsal pons, splenium of the corpus callosum, and the dorsal medulla.(Neuroradiol 2003;24:1615-7)

21. TAKE HOME MESSAGE : • Metronidazole used commonly to treat various anaerobic infections is considered to be safe but is not entirely benign. • Whenever patient presents with these symptoms, they should not be ignored and should be further workup thoroughly. • This kind of toxicity seen with metronidazole is not seen with other imidazoles like tinidazole and secnidazole. • Reversal of clinical as well as MRI abnormalities after cessation of drug intake is characteristic feature of metronidazole intoxication.

22. THANK YOU