[Table/Fig-5]:
Case studies of Metronidazole induced encephalopathy
| Country, Author, Year (in chronological order) | Age (Years) /Sex | Indication | Duration (days) | Cumulative Dose (grams) | Presentation | MRI Findings (T2 and FLAIR) | MRI Findings Diffusion restriction and ADC |
Follow up MRI Findings {Weeks after} | Neurological Outcome |
|---|---|---|---|---|---|---|---|---|---|
| USA, Frytak et al., [2], 1978(3 cases) | 77/F 75/F 52/F |
Inoperable pancreatic carcinoma Hepatic and pulmonary metastasis of rectal carcinoma Sensitizer for metastatic carcinoma of the stomach |
5 7 5 |
Not Mentioned 42 52 |
Seizures Seizures seizures |
Not done | Not done | Not done | Resolution Resolution Resolution |
| USA, Kusumi et al., [1], 1980 | 45/F |
B. fragilis anterior mediastinal abscess |
28 | 84.0 | Cerebellar dysfunction Alteration in mental status |
Not done | Not done | Not done | Resolution |
| USA, Ahmed et al., [8],1995 | 45/F | Blastocystis hominis diarrhea | 30 | 35.0 | Cerebellar dysfunction Alteration in mental status |
Symmetric Hyperintensities in cerebellar nuclei, genu and splenium of the corpus callosum and within frontal and parietal subcortical white matter |
Not mentioned | Complete and near complete normalization of lesions of corpus callosum and subcortical white matter respectively | Resolution |
| USA, Uhl et al., [49], 1996 | 65/F | Portosystemic encephalopathy | 90 | NS | Alteration in mental status | Not done | Not done | Not done | Resolution |
| USA, Horlen et al., [9], 2000 | 34/M |
B. fragilis meningitis + Bacteremia |
50 | 75.0 | Cerebellar dysfunction Alteration in mental status |
Hyperintensities in the inferior basal ganglia lateral to the hypothalamus and also below, behind, and lateral to the fourth ventricle | Not mentioned | Not done | Resolution |
| USA, Cecil et al., [21], 2002 | 17/M | Crohn disease | NS | NS | Cerebellar dysfunction | Symmetrical hyperintensities in the pars compacta of the substantia nigra, red nucleus, globus pallidus, putamen, caudate body, caudate heads and medial thalami. Faint contrast enhancement of the lesions in the red nucleus and cerebral peduncles. Proton MRS performed in the splenium and in the basal ganglia showed an elevated lactate resonance. | Not mentioned | Near-complete resolution of the previous abnormalities {after 13 weeks} | Resolution |
| USA, Woodruff et al., [50], 2002 | 74/M | Intra-abdominal abscesses | 28 | 42.0 | Cerebellar dysfunction | Hyperintensities in subcortical white matter and cerebellar dentate nuclei | Not mentioned | Complete normalization {after 5 weeks} | Resolution |
| Korea, Seok et al., [29], 2003 | 74/F | Rectovaginal fistula associated with Crohn disease | 90 | 90.0 | Cerebellar dysfunction | Hyperintensities in diffuse subcortical white matter, splenium, anterior commissure, basal ganglia, midbrain, cerebellar white matter and inferior olivary nuclei. (FLAIR) | Diffusion restriction in similar areas. ADC- Low | Complete normalization {after 17.5 weeks} | Near resolution |
| USA, Heaney et al., [32], 2003 | 74/M | Abdominal purulent abscess | 56 | 84.0 | Cerebellar dysfunction | Hperintensities in dentate nuclei, focal and confluent areas of nonenhancing signal intensity abnormality in the periventricular regions(believed to be related to chronic small vessel ischemic changes) | Diffusion restriction in dentate nuclei ADC-High |
Complete normalization {after 8 weeks} | Resolution |
| Japan, Ito et al., [51], 2004 | 54/F | H. pylori | 66 | 660.0 | Cerebellar dysfunction | Hperintensities in dentate nuclei | Not mentioned | Complete normalization {after 12 weeks} | Resolution |
| Korea, Kim et al., [43], 2004(2 cases) | a. 31/M | a. Crohn disease. | a. 6 + chronic use | a. 3 times usual dose + chronic use | a. Alteration in mental status | Hyperintensities in subcortical white matter and cerebellar dentate nuclei | Diffusion Restriction only in the subcortical white matter ADC- Low |
Complete normalization {after 8 weeks} | a. Impaired cognition |
| b. 46/M | b. Acute Cholangitis | b. 6 | b. Not Mentioned | b. Alteration in mental status | Hyperintensities in subcortical white matter and cerebellar dentate nuclei | Diffusion Restriction only in the subcortical white matter ADC- Low | Not mentioned | b. Vegetative state | |
| Belgium, De Bleecker et al., [6], 2005 | 20/M | Ulcerative colitis | 730 | 1110 | Cerebellar dysfunction | Hyperintensities in splenium and less conspicuously in the truncus and genu of the corpus callosum | Not mentioned | Partial resolution of the previous abnormalities{ after 8 months} | Impaired visual acuity |
| USA, Deenadayalu et al., [52], 2005 | 50/M | Peritonitis + hepatic Encephalopathy |
5 | 7.5 | Cerebellar dysfunction | Hyperintensities in cerebellar dentate nuclei | Not mentioned | Complete normalization {Time not mentioned} | Improvement |
| Korea, Kim et al., [28], 2007 (7 cases) | a. 54/M | a. Spontaneous bacterial Peritonitis | a. 15 | a. 22.5 | a. Cerebellar dysfunction Alteration in mental status |
Hyperintensities in B/L dentate nuclei, dorsal medulla, vestibular nucleus, abducens nucleus, superior olivary nucleus, tegmentum of midbrain, red nucleus and corpus callosum | Diffusion restriction in peripheral part of dentate nuclei, central part of splenium, pons and midbrain ADC- low in splenium; rest areas- high. | Not available | a. Improvement |
| b. 64/M | b.Intra-abdominal abscess | b. 17 | b. 25.5 | b. Cerebellar dysfunction | Hyperintensities in B/L dentate nuclei, dorsal medulla, inferior olivary nucleus, vestibular nucleus, superior olivary nucleus, tectum and tegmentum of midbrain, corpus callosum and subcortical white matter | Not available | Complete normalization {After 2 weeks 3 days} | b. Improvement | |
| c. 55/M | c. Ischemic colitis | c. 11 | c. 16.5 | c. Cerebellar dysfunction | Hyperintensities in B/L dentate nuclei, dorsal medulla, vestibular nucleus, abducens nucleus, superior olivary nucleus, tegmentum of midbrain, corpus callosum | Diffusion restriction in splenium and dentate nuclei ADC-Low in splenium and High in dentate |
Complete resolution of the hyperintense lesions in the dentate and pons but residual hyperintensity in splenium {After 2 weeks} | c. Improvement | |
| d. 71/M | d. DM foot | d. 17 | d. 25.5 | d. Cerebellar dysfunction | Hyperintensities in B/L dentate nuclei, dorsal medulla, vestibular nucleus, abducens nucleus, superior olivary nucleus and tectum | Diffusion restriction in dorsal medulla ADC-High |
Complete normalization {After 5 weeks} | d. Improvement | |
| e. 61/F | e. Pseudomembranous colitis | e. 24 | e. 36.0 | e. Cerebellar dysfunction | Hyperintensities in B/L dentate nuclei, tectum of midbrain | Diffusion restriction in tectum ADC- High |
Not available | e. Improvement | |
| f. 49/M | f. Crohn disease | f. 52 | f. 78.0 | f. Cerebellar dysfunction | Hyperintensities in B/L dentate nuclei, vestibular nucleus, abducens nucleus, superior olivary nucleus, tegmentum of midbrain and red nucleus | Diffusion restriction in tegmentum, red nucleus of midbrain and dorsal pons ADC- High |
Complete normalization {After 2 weeks} | f. Improvement | |
| g. 70/M | g. Brain abscess | g. 22 | g. 33.0 | g. Cerebellar dysfunction | Hyperintensities in B/L dentate nuclei, vestibular nucleus, superior olivary nucleus, tectum and tegmentum of midbrain, red nucleus and corpus callosum | Not available | Not available | g. Improvement | |
| Tunisia, Hammami et al., [53], 2007 | 51/M | Anal fistula | 21 | 31.5 | Cerebellar dysfunction Alteration in mental status |
Hyperintensities in B/L dentate nuclei, splenium, locus niger, periaqueductal region and bulbar region. | Diffusion restriction in dentate nuclei and splenium ADC- Low |
Complete normalization {after 4 weeks} | Resolution |
| Canada, Sarna et al., [54], 2009 (2 cases) | a. 72/F | a. Intra-abdominal abscess | a. 25 | a. 25.0 | a. Cerebellar dysfunction | a. Hyperintensities in B/L dentate nuclei | Not mentioned | Complete normalization {after 4 weeks} | a. Resolution |
| b. 54/M | b. Bronchiectasis | b. 60 | b. 60.0 | b. Cerebellar dysfunction, Seizure |
b. Hyperintensities in B/L dentate nuclei | Not mentioned | Complete normalization {after 12 weeks} | b. Resolution | |
| Korea, Lee et al., [30], 2009(9 cases) | a. 47/M | a. Decubitus ulcer | a. 50 | a. 100 | a. Cerebellar dysfunction | Hyperintensities in b/l dentate nucleus | Diffusion restriction was present in similar areas in 4 patients, in other 2 patients the sites of diffusion restriction and sites of T2/FLAIR hyperintensity did not match. ADC- obtained in 4 patients; In 3 patients low values were obtained in dentate, splenium and inferior colliculus and in 1 patient high value was noted in dentate nucleus |
a. Not available | a. Improvement |
| b. 61/M | b. Liver abscess | b. 60 | b. 120 | b. Cerebellar dysfunction | Hyperintensities in b/l dentate nucleus, Corpus Callosum | b. Complete normalization except for lesion of corpus callosum {After 3 days} | b. Improvement | ||
| c. 76/F | c. Liver abscess | c. 50 | c. 100 | c. Cerebellar dysfunction | Hyperintensities in b/l dentate nucleus, inferior colliculus, | c. Complete normalization {After 8 days} | c. Improvement | ||
| d. 78/F | d. Lung abscess | d. 40 | d. 80 | d. Cerebellar dysfunction | Hyperintensities in b/l dentate nucleus, inferior colliculus, corpus callosum, cerebral white matter | d. Not available | d. Improvement | ||
| e. 64/F | e. Peritoneal abscess | e. 50 | e. 100 | e. Cerebellar dysfunction | Hyperintensities in b/l dentate nucleus, inferior colliculus, Pons | e. Complete normalization {After 15 days} | e. Improvement | ||
| f. 68/M | f. Lung abscess | f. 44 | f. 88 | f. Cerebellar dysfunction | Hyperintensities in b/l dentate nucleus, inferior colliculus | f. Complete normalization {After 4 days} | f. Improvement | ||
| g. 60/M | g. Brain abscess | g. 60 | g. 120.0 | g. Cerebellar dysfunction | Hyperintensities in b/l dentate nucleus, inferior colliculus, medulla | g. Complete normalization {After 15 days} | g. Improvement | ||
| h. 43/M | h. Peritoneal abscess | h. 30 | h. 45 | h. Cerebellar dysfunction | Hyperintensities in b/l dentate nucleus, inferior colliculus, pons | h. Not available | h. Improvement | ||
| UK, Graves et al., [55], 2009 | 61/M | Klebsiella wound infection | 77 | 92.4 | Cerebellar dysfunction | Hyperintensities in cerebellar dentate nuclei | Not mentioned | Not done | Resolution |
| Chile, Galvez et al., [14], 2009 | 60/M | Hepatic encephalopathy (Known case of Hepatitis C) | Not Mentioned | Not Mentioned | Cerebellar dysfunction, increase in gait ataxia, chorea of the face and limb and myoclonus |
FLAIR image- Hyperintense lesions on cerebellum dentate nuclei. T2-weigthed images - hyperintense lesions involving the bilateral cerebellum dentate nuclei, inferior colliculus, and corpus callosum | Diffusion-restriction in cerebellar dentate nuclei and inferior colliculus | Complete resolution of the hyperintense lesions in the cerebellum and brainstem {after 4 weeks} | Improvement |
| Korea, Bahn et al., [33], 2010 | 52/M | Brain Abscess | 20 | 40 | Cerebellar dysfunction | Hyperintensities in B/L dentate nuclei of cerebellum and splenium | Diffusion-restriction in pons, splenium , and the right trigone peri-ventricular white matter ADC- low in the splenium and right trigone peri-ventricular white matter |
Complete normalization | Resolution |
| Netherlands, Groothoff et al., [31], 2010 | 38/F |
B. fragilis wound of Osteomyelitis |
70 | 132.0 | Cerebellar dysfunction alteration in mental status, seizures |
FLAIR Hyperintensities in bilateral centrum semiovale and cerebellar peduncles. | Not mentioned. | No improvement(CT scan at 7 week) | Died |
| India, Kalia et al., [56], 2010 | 43/M | Amoebic liver abscess | 60 | 72.0 | Cerebellar dysfunction | Symmetrical hyperintensities of dentate nuclei, dorsal pons, and splenium | Diffusion restriction in similar areas. ADC- Low | Not available | Resolution |
| Korea, Cheong et al., [46], 2011 | 57/M | Alchoholic cirrhosis, hepatic encephalopathy | 26 | 30 | Cerebellar dysfunction, alteration in mental status | Hyperintensity in B/L dentate nuclei, splenium | Diffusion restriction in corpus callosum ADC: Not Mentioned |
Complete normalization {after 5 weeks} | Resolution |
| Sweden, Khodakaram et al [57], 2011 | 50/M | Abscess of appendix | 7 | 8 | Cerebellar dysfunction, loss of hearing and vertigo | Hyperintensity in B/L dentate | Not Mentioned | Complete normalization { after 8 weeks} | Resolution |
| Korea, Park et al., [58], 2011 | 67/M | Liver abscess | 83 | 127.5 | Cerebellar dysfunction | Hyperintensity in B/L dentate nuclei, splenium (FLAIR) | Diffusion restriction in Splenium; ADC: low |
Near normalization of dentate, but residual hyperintensity of splenium(FLAIR and DWI); Normalization of ADC { after 1 week} | Improvement |
| Japan, Yamamoto et al., [59], 2012 | 68/M | Liver Abscess | 19 | 28.5 | Cerebellar dysfunction, alteration in mental status | Hyperintensity in B/L dentate nuclei, (and hyperintensity of basal ganglia on T1) | Not Mentioned | Complete normalization of dentate lesions, basal ganglia lesions: Not Mentioned {after 4 weeks} | Resolution |
| Korea, Jang et al., [48], 2012 | 60/F | Anaerobic Brain Abscess(known case of Chronic hepatitis B, Liver cirrhosis) | 77 | 171.5 | Cerebellar dysfunction, hemiparesis | Hyperintensity in B/L dentate nuclei, dorsal medulla, pons, splenium, asymmetric lesions in midbrain, thalamus, putamen, subcortical white matter | Diffusion restriction in splenium, midbrain, thalamus, subcortical white matter. ADC low in subcortical white matter |
Complete normalization except for lesion of splenium { after 4 weeks} | Resolution |
| USA, Knorr et al., [7], 2012 | 63/M | Clostridium difficile associated diarrhea (Known patient of ESLD with Hepatitis C) | 14 | 7.5 | Cerebellar dysfunction, diplopia, facial palsy | Hyperintensity in B/L dentate nuclei, inferior colliculi and splenium | Diffusion restriction in the splenium | Complete normalization {after 6 weeks} | Resolution |
| Turkey, Erdener et al., [41], 2013 | 64/F | Ulcerative colitis | 315 | 450 | Intermittent ataxia and dysarthria | Hyperintensity of corpus Callosum, dentate nuclei |
Diffusion restriction of corpus Callosum, ADC- low |
Complete normalization of lesions of Dentate nuclei, Less prominent hyperintensity of corpus callosum, cystic degeneration in the genu of the corpus callosum. {13 weeks later} |
Not Mentioned |
| India, Iqbal et al., [60], 2013 | 78/M | Amoebic liver abscess | 35 | 84 | Cerebellar dysfunction, headache and Seizures | Hyperintensity in B/L dentate nuclei, dorsal midbrain and pons | Diffusion restriction in B/L dentate nuclei, dorsal midbrain and pons, ADC- Normal | Complete normalization {12 days later} | Improvement |
| USA, Godfrey et al., [61], 2015 | 65/F | Clostridium difficile colitis | 42 | 63 | Alteration in mental status | Hyperintensity in B/L dentate nuclei, superior cerebellar peduncle, splenium and parietal subcortical white matter | Diffusion restriction in superior cerebellar peduncle, splenium and parietal subcortical white matter | Resolution of signal intensity of cerebellar peduncles and dentate nuclei {17.5 weeks later} | Resolution |
| India, Haridas et al., [62], 2015 | 51/F | Irritable bowel syndrome | 5 | 7.5 | Alteration in mental status | Hyperintensity in B/L dentate nuclei | Not Mentioned | Not done | Resolution |
| Japan, Yagi et al., [15], 2015 | 36/M | Intractable pulmonary empyema (Known case of Alcoholic liver cirrhosis) | 21 | 42 | Cerebellar dysfunction, Alteration in mental status, Myoclonus |
Hyperintensities of Dentate nucleus, superior cerebellar peduncles, dorsal pons, periaqueductal area, splenium of the corpus callosum (FLAIR) |
Diffusion restriction in similar areas hyperintense in FLAIR | Reduction in hyperintensities {at 9 weeks} | Myoclonus disappeared 3 days after the discontinuation of Metronidazole. There was slight neurological improvement, but deteriorated due to liver failure and died about 2 months later |
| India, Senthilkumaran et al., [63], 2015 | 39/M | Amoebic liver abscess | 28 | 67.2 | Cerebellar dysfunction, alteration in mental status |
Hyperintensity in B/L dentate nuclei, splenium | Diffusion restriction in B/L dentate nuclei, splenium | Complete normalization {17.5 weeks later} | Resolution |
| USA, Hobbs et al., [42], 2015 | 69/F | Spontaneuos bacterial peritonitis, gangrenous cholangitis (known case of Chronic hepatitis B, Liver cirrhosis) | 22 | 33 | Alteration in mental status | B/L symmetrical hyperintensities of subcortical white matter, corpus callosum, internal capsule, midbrain, superior cerebellar peduncles and bilateral dentate nuclei |
Perfusion arterial spin labeling revealed hyperintensity in bilateral dentate nuclei. |
Relative improvement of Diffusion restriction in the dentate nuclei but persistent T2 hyperintensity in this area. New restricted diffusion in the cortex in a middle cerebral artery- posterior cerebral artery border zone pattern bilaterally, right worse than left. Perfusion arterial spin labeling imaging demonstrated hyperperfusion of uncertain significance in these regions.{ 1 week later) |
Died on hospital day 31 (24 days from metronidazole discontinuation). |
| Japan, Furukawa et al., [34], 2015 | 52/M | Retroperitoneal abscess | 120 | 250 | Cerebellar dysfunction, cognitive impairment | Hyperintense lesions in the bilateral cerebellar dentate nucleus, corpus callosum, and subcortical white matter . Multiple contrast-enhanced T1-weighted lesions observed in the corpus callosum. |
Diffusion- Not mentioned. ADC-low in corpus callosum and white matter | Near normalization of lesions in the bilateral dentate nucleus, and decrease in size of lesions in corpus callosum and white matter, Multiple cystic lesions in the corpus callosum and bilateral white matter |
Improvement |
| India, Roy et al., 2015(this study-4 cases) | 43/M | Recurrent Amoebic dysentery(1st episode resolved after 7 days of therapy but recurred after a gap of 1 week) | 6 | 15.6 | Cerebellar dysfunction, alteration in mental status | Hyperintense lesions in the bilateral cerebellar dentate nucleus, splenium of corpus callosum, bilateral caudate head and body, lentiform nuclei and inferior olive, and subcortical white matter . | Diffusion restriction in bilateral cerebellar dentate nucleus, splenium of corpus callosum, bilateral caudate head and body, lentiform nuclei and and subcortical white matter. ADC-Not available |
Complete normalization {4 weeks later} | Resolution |
| 50/M | Irritable bowel syndrome(chronic intermittent intake(~400 mg/day)-self medication for 18 months), recent increase in dose(2g/day) | ~554 | 244 | Alteration in mental status, peripheral neuropathy | Hyperintense lesions in the splenium of corpus callosum |
Diffusion restriction in splenium of corpus Callosum ADC-Black |
Complete normalization {3 weeks later} | Resolution of alteration in sensorium and improvement in symptoms of neuropathy | |
| 40/M | Irritable bowel syndrome(chronic intermittent intake(~400 mg/day)-self medication for 8 years) | ~2848 | 1139.2 | Episodic dysarthria and ataxia, peripheral neuropathy | Hyperintense lesions in the genu and body of corpus callosum |
Diffusion restriction in the genu and body of corpus callosum ADC-White |
Minimal Resolution {8 weeks later} | No further episodic ataxia and improvement in symptoms of neuropathy | |
| 69/M | Amoebic liver abscess | 7 | 14 | Cerebellar dysfunction, alteration in mental status | Hyperintense lesions in the bilateral cerebellar dentate nucleus (faint), splenium of corpus callosum, and inferior colliculus. | Diffusion restriction in splenium of corpus callosum ADC-Black | Not available | Resolution |
M- male, F-female, Cerebellar dysfunction- Dysarthria, ataxia, ESLD-End Stage Liver Disease, B/L- Bilateral, ADC- Apparent diffusion coefficient, FLAIR- Fluid-attenuated inversion recovery