Metronidazole Encephalopathy EEG Features: A Case Report with Systematic Review of the Literature

Abstract

Metronidazole-induced encephalopathy (MIE) is a rare and often under-recognized iatrogenic condition. The diagnosis should be considered in metronidazole-treated patients presenting with acute encephalopathy, unprovoked seizures and cerebellar signs. While typical magnetic resonance imaging (MRI) findings strongly support the diagnosis, electroencephalography (EEG) features have been rarely reported and poorly described. We present a longitudinal EEG assessment in one patient with encephalopathy due to metronidazole toxicity who presented a peculiar EEG pattern presentation and evolution. During the acute phase of encephalopathy, the EEG showed a monomorphic, sharply contoured theta activity symmetrically represented over frontal regions with an anterior-posterior progression which evolved in parallel with clinical worsening. Together with a systematic review of the literature, we discuss whether this EEG activity may represent a distinct neurophysiological correlate of 'cerebellar encephalopathy'.

Keywords: EEG; MIE; drug-induced seizure; metronidazole; metronidazole-induced encephalopathy.

Figure 1

Standard 19-channel electroencephalography (EEG) recordings of our patient (high pass filter: 1.6 Hz; low pass filter: 50 Hz; left panel), standardized low-resolution brain electromagnetic tomography (sLORETA) distributed solution of normalized relative theta (5–7 Hz) power density at the cortical voxels (middle panel) and source analysis of averaged theta waves (right panel). LORETA computes 3D linear solutions for the EEG inverse problem within a 3-shell spherical head model including scalp, skull and brain compartments. (A) shows the EEG obtained after our first examination characterized by frequent and very brief runs of bilateral and symmetric monomorphic sharp theta activity over frontal regions. Serial EEGs, performed 8 (B) and 12 days (C) later, confirmed the presence of rhythmic monomorphic sharp theta activity, organized in more prolonged sequences. sLORETA distributed solution for theta frequency power spectrum confirms the anterior distribution of slow activity. sLORETA source analysis of averaged theta waves shows an anterior distribution of electrical generators for the first 2 EEGs as well (A,B); while the last EEG displays deeper electrical generators (bilateral thalami and subcortical white matter, (C)) which may suggest the involvement of dentate-thalamo-cortical tracts. Values in this figure represent the relative power of each source. At each vertex of the cortex surface, the value between 0 and 1 indicates the contribution of the current frequency band to the total power in the signal. Panel (D) shows a 1-month follow-up EEG. No abnormalities are noticed. sLORETA solution shows normalization of the theta-band anterior distribution as well. sLORETA solution was performed using the Brainstorm toolbox for Matlab and age-appropriate head templates [7]. The left side of cortical images and 2D magnetic resonance imaging (MRI) corresponds to the left hemisphere.

Figure 2

A 1.5 Tesla brain MRI. Fluid-attenuated inversion recovery (FLAIR) sequences showing hyperintensity in (A) bilateral dentate nuclei of the cerebellum (arrows) and (B) dorsal midbrain (arrowhead). A follow-up MRI performed one month after metronidazole discontinuation did not show any abnormalities (C,D).

Figure 3

PRISMA flowchart of the selection of the studies for this review.