Case: 53-year-old Man with Ataxia

00:01 Let's start with a case to understand why this information is important.

00:05 This is a 53-year-old man with liver disease and recent hospitalization for osteomyelitis, who was placed on metronidazole and moxifloxacin for six weeks.

00:17 The patient was recovering well until about two weeks ago, when he began to develop gait ataxia and dysarthria.

00:23 So some cerebellar signs.

00:26 This is slowly worsened to the point that he is having trouble walking.

00:29 Exam shows truncal ataxia, difficulty with keeping himself upright dysarthric speech, saccadic overshoot on eye movement examination, so he's having trouble coordinating his eye movements.

00:41 Otherwise, neurologic exam is unremarkable.

00:44 MRI is performed and reveals T2-weighted hyperintense lesions in the bilateral deep cerebellar gray matter.

00:52 So what's the most likely diagnosis? Well, as with other cases of the brain and cerebellum, the timeline of onset is important.

01:00 This is a subacute onset condition.

01:03 It's not acute like a stroke, or an intoxication or trauma, not chronic, like a degenerative cerebellar disease.

01:09 This sounds like something more in the inflammatory, toxic, or metabolic category.

01:16 The patient's description is that of cerebellar disequilibrium.

01:20 There's prominent gait ataxia and imbalance, dysarthric of speech.

01:24 And on examination, we find all of those cerebellar findings.

01:28 So this isn't vertigo. It's not syncope, we're dealing with disequilibrium.

01:34 And then importantly, for this case, are the imaging findings.

01:37 We see edema or problems in the deep cerebellar nuclei, not in the hemispheres of the white matter, but in those deep cerebellar nuclei.

01:46 So we're looking for a problem that has a predilection for the nuclei of the cerebellum.

01:52 So what is the most likely diagnosis? Is this metronidazole-induced to cerebellar toxicity? Is this a post-infectious cerebellitis? Is this a cerebellar stroke? Or could this be hepatic encephalopathy? We don't like hepatic encephalopathy.

02:08 In liver disease, which the patient has can cause hyperammonemia and hepatic encephalopathy.

02:14 But that's an encephalopathy syndrome.

02:17 Patients are confused and altered with varying degrees of sedation.

02:21 This patient has no encephalopathy, and isolated cerebellar signs.

02:26 So this is inconsistent with hepatic encephalopathy.

02:30 This doesn't sound like a cerebellar stroke.

02:32 Strokes again, are acute in onset, and this was more subacute in its onset.

02:37 In addition, the MRI changes are very specific to the deep cerebellar gray matter nuclei.

02:42 Their bilateral and symmetric.

02:44 And typically we think of a stroke as being asymmetric on one side of the other, and often affecting the circumferential vessels as they course around the cerebellum and affecting the hemispheres and hemispheric function.

02:58 Post infectious cerebellitis can be seen after an infection, but that's typically not something we see after an osteomyelitis.

03:05 Typically, we see this after some type of viral infection.

03:08 And importantly, post-infectious cerebellitis affects the hemispheres.

03:13 Sometimes one or the other hemispheres, and sometimes bilaterally, but the hemispheres of the predominant area that are affected.

03:20 And here we have a specific process that has a tropism or predilection for the deep gray matter of the cerebellum.

03:28 And this is a typical case of metronidazole-induced cerebellar neurotoxicity.

03:34 This is an uncommon condition, but we see it frequently.

03:37 Metronidazole has a predilection for the dentate nucleus, and the deep gray matter structures.

03:42 And so as neurologist, and when evaluating neurologic patients with neurologic disease, this is a condition we want to understand.

03:50 Let's talk for a minute about Metronidazole-Associated Cerebellar Neurotoxicity.

03:55 It's one of those conditions that reminds us of the importance for understanding, what those deep cerebellar nuclei are? This is a subacute onset cerebellar ataxia.

04:05 That presents in patients who have been taking metronidazole.

04:08 Often at moderate to high doses for a extended period of time.

04:12 Patients present in a subacute fashion over several days to weeks, with primary ataxia.

04:18 Both affecting the trunk, as well as appendicular function.

04:22 And symptoms occurred during a prolonged course of metronidazole.

04:27 Imaging is very specific and shows us the T2-weighted or FLAIR hyperintensity, as we saw in this case, that affects the bilateral dentate nuclei.

04:35 Those are susceptible to this metronidazole induced toxicity.

04:40 What's going on pathologically? Well we see edema or swelling within the dentate nuclei that caused this characteristic imaging finding.

04:47 Typically this resolves with removal of the offending agent stopping the metronidazole, and in patients improve gradually, over the next several weeks and sometimes months.

04:57 Many returning back to normal function.