Table 2.
Summary of neurological features, investigations, treatments, and outcomes
| Publication | Age | Sex | Myoclonus | Cerebellar ataxia | Other neurological features | Brain Imaging | Electrophysiology | Treatment | Outcome | Proposed etiology | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Latency | Distribution | Activation | Latency | Distribution | |||||||||
| Cases with myoclonus and ataxia | |||||||||||||
| Chan et al. (case report) | 44 | M | 12 days | Face, upper extremities, lower extremities | Action, posture, tactile stimuli | 12 days | Limbs, gait | Saccadic intrusions, attention and memory impairment |
CT: Unremarkable MRI: Unremarkable |
EEG: Minor generalized slowing | Methylprednisolone 1000 mg IV daily for 5 days (day 6–10 after symptom onset); clonazepam 0.75 PO BID starting day 10; levetiracetam 1000 mg PO BID starting day 14 | Improvement of spontaneous myoclonus after methylprednisolone. Myoclonus improved after clonazepam and levetiracetam. Discharged day 18 after symptom onset, myoclonus and ataxic gait resolved within 1 week after discharge | Post-infectious |
| Anand et al. 2020 [9] | 71 | M | Unclear | Generalized | Action | Onset | Gait | Confusion | MRI: Diffuse pachymeningeal enhancement | EEG: Mild diffuse background slowing | Levetiracetam, valproic acid |
Myoclonus: Resolved after 14 days Ataxia: Not reported |
Myoclonus: Post-infectious, metabolic, hypoxic Ataxia: COVID-19 presentation |
| Chaumont et al. 2020 [10] | 62 | M | Unclear, immediately after extubation | Upper extremities | Posture, action | Unclear, immediately after extubation | Unspecified | Confusion, dysexecutive syndrome, memory deficit, swallowing disorder, left facial palsy, right upper limb and left-sided weakness, lower limb areflexia, upper limb hyperreflexia, dysautonomia | MRI: Small subcortical ischemic stroke in right middle cerebral artery territory |
EEG: Global slowing EMG: Demyelinating asymmetric motor polyradiculoneuropathy of limbs and axonal sensorimotor neuropathy of limbs |
IVIG 0.4 mg/kg daily for 5 days (day 23–27 after symptom onset) |
Myoclonus: Unclear, persisted 3 weeks after discharge Ataxia: Not reported |
Post-infectious |
| Chaumont et al. 2020 [10] | 72 | M | Unclear, immediately after extubation | Upper extremities | Posture, action | Unclear, immediately after extubation | Unspecified | Confusion, paranoid delusion, visual and auditory hallucinations, frontal syndrome, memory deficit, swallowing disorder, tetraparesis, slowed saccades, generalized hyperreflexia, neurogenic pain, dysautonomia | MRI: Unremarkable |
EEG: Global slowing EMG: Demyelinating motor polyradiculoneuropathy and axonal sensorimotor neuropathy of limbs |
IVIG 0.4 mg/kg daily for 5 days (day 18–22 after symptom onset) |
Myoclonus: Unclear, persisted 3 weeks after discharge Ataxia: Not reported |
Post-infectious |
| Chaumont et al. 2020 [10] | 50 | M | 48 days | Upper extremities | Posture, action | 48 days | Unspecified | Confusion, paranoid delusion, frontal syndrome, memory deficit, swallowing disorder, tetraparesis, slowed saccades, generalized hyperreflexia, dysautonomia | MRI: Unremarkable |
EEG: Global slowing EMG: Motor denervation of limbs. Normal motor evoked potential amplitude |
IVIG 0.4 mg/kg daily for 5 days (day 23–27 after symptom onset) |
Myoclonus: Unclear, persisted 3 weeks after discharge Ataxia: Not reported |
Post-infectious |
| Chaumont et al. 2020 [10] | 66 | M | 40 days | Upper extremities | Posture, action | 20 days | Unspecified | Confusion, paranoid delusion, visual hallucinations, frontal syndrome, memory deficit, tetraparesis, upper limb hyperreflexia, lower limb areflexia, dysautonomia | MRI: Unremarkable |
EEG: Normal EMG: Demyelinating motor polyradiculoneuropathy of limbs |
IVIG 0.4 mg/kg daily for 5 days (day 6–10 after symptom onset) |
Myoclonus: Unclear, persisted 3 weeks after discharge Ataxia: Not reported |
Post-infectious |
| Delorme et al. 2020 [11] | 72 | M | 15 days | Upper extremities | None | 15 days | Unspecified | Psychomotor agitation, cognitive and behavioural frontal lobe syndrome |
MRI: Unremarkable FDG-PET: Bilateral prefrontal and left parietotemporal hypometabolism, cerebellar vermis hypermetabolism |
EEG: Normal | IVIG 2 g/kg | Myoclonus and ataxia: Resolved | Post-infectious |
| Dijkstra et al. 2020 [12] | 44 | M | 2 weeks | Face, speech, arms, trunk | Action, tactile stimuli, auditory stimuli | 2 weeks | Limbs, gait | Saccadic intrusions, ocular flutter, attention and memory deficits, perseveration, impulsivity, anxiety, hypervigilance, insomnia | MRI: Unremarkable | N/A | Methylprednisolone 1000 mg IV daily for 5 days (day 7–11 after symptom onset); IVIG 0.4 g/kg daily for 3 days (day 15–17 after symptom onset) | Myoclonus and ataxia: Slow response to methylprednisolone, resolved within 2 months | Post-infectious |
| Grimaldi et al. 2020 [13] | 72 | M | 17 days | Proximal limbs | Action, stimuli | 17 days | Limbs | Dysarthria |
MRI: Unremarkable FDG-PET: Putamen and cerebellum hypermetabolism, diffuse cortical hypometabolism |
EEG: Diffuse background slowing | IVIG 0.4 g/kg daily for 5 days (day 6–10 after symptom onset); methylprednisolone 1000 mg IV daily for 5 days (day 13–17 after symptom onset) | Myoclonus and ataxia: No response to IVIG; cessation of myoclonus and upper limb dysmetria by day 20 after symptom onset | Post-infectious |
| Sanguinetti and Ramdhani 2020 [14] | 57 | M | Unclear, at least 5 days | Upper extremities, lower extremities | Action | Unclear, at least 5 days | Gait | Opsoclonus | MRI: Unremarkable | N/A | Clonazepam; IVIG 0.4 g/kg daily for 5 days; methylprednisolone 40 mg BID | Myoclonus and ataxia: Improved over hospitalization | Post-infectious |
| Schellekens et al. 2020 [15] | 48 | M | 13 days | Face, trunk, limbs | Posture, action | 13 days | Limbs, gait | Saccadic intrusions, hypermetric saccades | MRI: Unremarkable | N/A | Levetiracetam |
Myoclonus: Resolved within days of starting levetiracetam Ataxia: Improved by 49 days after symptom onset |
Post-infectious |
| Shah and Desai 2020 [16] | Middle-aged | M | Unclear, at least 3 weeks | Unspecified | None | Unclear, at least 3 weeks | Speech, limbs, trunk, gait | Opsoclonus | MRI: Unremarkable | N/A | Methylprednisolone 1000 mg IV daily, valproate 20 mg/kg/day, clonazepam 2 mg/day, levetiracetam 2000 mg/day | Myoclonus and ataxia: Resolved in 1 week after treatment | Post-infectious |
| Cases with myoclonus, without ataxia | |||||||||||||
| Anand et al. 2020 [9] | 47 | M | 8 days | Generalized | Stimuli | None | CT: No acute | N/A | Ketamine, dexmedetomidine | Resolved after 2 days | Post-infectious, metabolic, medication, hypoxic | ||
| Anand et al. 2020 [9] | 28 | M | 8 days | Generalized | Stimuli | None | CT: No acute | N/A | Lorazepam, midazolam, dexmedetomidine | Resolved after 1 day | Post-infectious, metabolic, medication, hypoxic | ||
| Anand et al. 2020 [9] | 73 | M | 10 days | Torso, upper extremities | Stimuli | None | CT: No acute | N/A | Levetiracetam | Resolved after 2 days | Post-infectious, metabolic, medication, hypoxic | ||
| Anand et al. 2020 [9] | 64 | M | 11 days | Upper extremities | Stimuli | None | MRI: Equivocal right temporal T2 hyperintensity | N/A | Dexmedetomidine | Resolved after 1 day | Post-infectious, metabolic, medication, hypoxic | ||
| Anand et al. 2020 [9] | 66 | M | 12 days | Upper extremities, face | None | None | CT: No acute | N/A | Dexmedetomidine | Resolved after 2 days | Post-infectious, metabolic, medication, hypoxic | ||
| Anand et al. 2020 [9] | 72 | M | 16 days | Generalized | Stimuli | None | CT: No acute | EEG: Muscle artifact | Valproic acid, levetiracetam, lorazepam, dexmedetomidine | Improved myoclonus, though reintubated | Post-infectious, metabolic, medication, hypoxic | ||
| Anand et al. 2020 [9] | 62 | M | 12 days | Generalized | Stimuli | None | N/A | EEG: Generalized dysfunction, occasional low-amplitude sharp transients, myogenic activity | Valproic acid, primidone, clonazepam, lorazepam | Improved starting at least 10 days after symptom onset | Post-infectious, metabolic, medication, hypoxic | ||
| Borroni et al. 2020 [17] | 54 | F | Within 2 weeks | Diaphragm, left limbs | Posture | None | MRI: Unremarkable |
EEG: Normal EMG: Rhythmic and synchronous contractions of diaphragm at 3 Hz with abdominal contractions |
Clonazepam 0.5 mg TID | Significant benefit of clonazepam | Post-infectious | ||
| Borroni et al. 2020 [17] | 80 | M | 23 days | Diaphragm | None | None | CT: No acute | EEG: Lateralized periodic discharges synchronous and asynchronous with diaphragmatic myoclonus | Levetiracetam 1000 mg BID | Resolved after 3 days of levetiracetam, with improvement of EEG features | Post-infectious | ||
| Cuhna et al. 2020 [18] | 67 | M | Unclear, after ICU discharge | Extremities | None | Mild right hemiparesis |
MRI: Corpus callosum microbleeds DaTScan: Normal |
EMG: Myoclonus with 24–44 ms duration and post-myoclonic inhibition 36–86 ms. Duration consistent with cortical–subcortical myoclonus | Not reported | Not reported | Post-infectious, metabolic, hypoxic | ||
| Cuhna et al. 2020 [18] | 66 | F | Unclear, after ICU discharge | Upper extremities | Posture, action | Critical illness myopathy |
MRI: Deep and peripheral microbleeds DaTScan: Normal |
EMG: Myoclonus with 70–94 ms duration and long loop C-reflex with 50 ms latency. Duration consistent with cortical-subcortical myoclonus, long loop C-reflex consistent with cortical myoclonus | Not reported | Not reported | Post-infectious, metabolic, hypoxic | ||
| Khoo et al. 2020 [19] | 65 | F | 7 days | Face, tongue, upper extremities, lower extremities | Tactile stimuli, visual stimuli, auditory stimuli | Confusion, ocular flutter, convergence spasm with miosis, expressive aphasia, perseveration, echopraxia, visual hallucinations | MRI: Unremarkable | N/A | Levetiracetam 750 mg BID and clonazepam 0.25 mg BID; methylprednisolone 1000 mg IV daily for 3 days (day 14–16 after symptom onset), then prednisone 1 mg/kg PO daily | Partially improved after levetiracetam and clonazepam. Progressively improved after corticosteroids, discharged 10 days after | Post-infectious | ||
| Méndez-Guerro et al. 2020 [20] | 58 | M | 34 days | Upper extremities | Action | Postural tremor upper extremities, decreased consciousness, opsoclonus, upgaze restriction, round the house vertical saccades, impaired smooth pursuit, tetraparesis, right-sided hypokinetic-rigid syndrome, hypomimia, decreased blinking, glabellar tap |
CT/CTA: Unremarkable MRI: Normal DaTSPECT: Bilateral decrease in presynaptic dopamine uptake in putamen |
EEG: Unremarkable EMG: 7 Hz rest tremor (completed after myoclonus resolved) |
None | Spontaneously resolved | Post-infectious | ||
| Muccioli et al. 2020 [21] | 58 | M | At least 23 days | Multifocal | Action, tactile stimuli | None | MRI: Cerebral small-vessel disease |
EEG: Unremarkable EMG: Myoclonus with 140–220 ms duration. Duration consistent with subcortical myoclonus |
Clonazepam and levetiracetam | Marked improvement within 5 days of starting treatment | Post-infectious | ||
| Rábano-Suárez et al. 2020 [22] | 63 | M | 9 days | Face, limbs (positive, negative) | None | None |
CT: Unremarkable MRI: Unremarkable |
EEG: Mild diffuse slowing | Propofol; levetiracetam, valproic acid, clonazepam; methylprednisolone 1000 mg IV daily for 5 days; plasmapheresis, 5 treatments | No improvement with levetiracetam, valproic acid, clonazemam. Slight improvement with methylprednisolone. Improvement after plasmapheresis | Post-infectious | ||
| Rábano-Suárez et al. 2020 [22] | 88 | F | 3 weeks | Face, limbs (positive, negative) | Action, tactile stimuli, auditory stimuli | None | CT: Unremarkable | EEG: Mild diffuse slowing | Methylprednisolone 250 mg IV for 3 days | Resolved after methylprednisolone | Post-infectious | ||
| Rábano-Suárez et al. 2020 [22] | 76 | M | 11 days | Face, limbs (positive, negative) | Action, tactile stimuli, auditory stimuli | None |
CT: Unremarkable MRI: Unremarkable |
EEG: Mild diffuse slowing | Clonazepam and levetiracetam; methylprednisolone 250 mg IV for 3 days | No improvement with clonazepam or levetiracetam. Spontaneous progressive improvement, 2 weeks after methylprednisolone | Post-infectious | ||
| Ros-Castelló et al. 2020 [23] | 72 | F | 35 days | Upper extremities (positive), lower extremities (negative) | Action, tactile stimuli, auditory stimuli | None | MRI: Cortical and brainstem ischemic lesions | N/A | Clonazepam | Almost resolved after 2 days of clonazepam | Hypoxic | ||
| Cases with ataxia, without myoclonus | |||||||||||||
| Ashraf and Sajed 2020 [24] | 26 | F | Onset | Right limb, gait | Headache, vomiting, right numbness and tingling, right weakness, dysarthria |
CTA: Unremarkable MRI: Acute right cerebellar and cerebellar peduncle infarct MRA: Narrowing of right superior cerebellar artery |
N/A | Aspirin, clopidogrel, statin | Not reported | Ischemic stroke | |||
| Balestrino et al. 2020 [25] | 73 | M | Onset | Gait | Confusion, drowsiness | CT: Unremarkable | EEG: Sporadic, focal polymorph delta in anterior-frontal left, sporadic spikes without epileptic correlate in frontotemporal lobe, predominately left | No specific neurological treatment. Treatment with lopinavir/ritonavir, chloroquine, steroids, levofloxacin | Resolved within 6 weeks | COVID-19 presentation | |||
| Delorme et al. 2020 [11] | 60 | F | Onset | Limbs, gait | Psychomotor agitation, anxiety, depressed mood, dysexecutive syndrome, dysarthria, nysgtagmus |
MRI: Right mesial sclerosis (known) FDG-PET: Hypometabolism in bilateral orbitofrontal cortices, hypermetabolism in bilateral striatum and cerebellar vermis |
EEG: Normal | Pulse corticosteroids 2 mg/kg daily for 3 days | Resolved within a few days of starting corticosteroids | COVID-19 presentation | |||
| Diezma-Martín et al. 2020 [26] | 70 | M | 17 days | Ataxia/tremor of voice, upper extremities, lower extremities, gait | Orthostatic tremor | MRI: Unremarkable | N/A | Clonazepam | Slight improvement with clonazepam. Improved slowly in month after discharge | Post-infectious | |||
| Fadakar et al. 2020 [27] | 47 | M | 3 days | Limbs, gait, trunk | Vertigo, headache, dysarthria, hypermetric saccades, saccadic pursuit, loss of optokinetic nystagmus, impaired vestibular suppression response, end-gaze rotational nystagmus | MRI: FLAIR hyperintensities in bilateral cerebellar hemispheres and vermis, cerebellar cortical meningeal enhancement | N/A | No specific neurological treatment. Treatment with lopinavir/ritonavir 400/100 mg BID for 14 days | Marked improvement, within 14 days of treatment start, continuing to 1 month | Para-infectious, acute cerebellitis | |||
| Fernández-Domínguez et al. 2020 [28] | 74 | F | 12–15 days | Gait | Lower extremity areflexia | MRI: Unremarkable | EMG: Slight F-wave delay in upper limbs | IVIG 20 g daily for 5 days | Improvement after IVIG | Miller Fisher syndrome variant | |||
| Gutiérrez-Ortiz et al. 2020 [29] | 50 | M | 3 days | Gait | Right internuclear ophthalmoplegia, right oculomotor nerve palsy, perioral paresthesia, generalized areflexia | CT: Unremarkable | N/A | IVIG 0.4 g/kg daily for 5 days (day 5–9 after symptom onset) | Resolved within 2 weeks after IVIG | Miller Fisher syndrome variant | |||
| Hayashi et al. 2020 [30] | 75 | M | Onset | Limbs, gait | None | MRI: Diffusion restriction in the splenium of corpus callosum | N/A | No specific neurological treatment | Resolved 2 days after onset | COVID-19 presentation | |||
| Kopscik et al. 2020 [31] | 31 | M | Onset | Limbs, gait | Bilateral cranial nerve VI palsy, vertical nystagmus, left cranial nerve VII palsy, left cranial nerve XII dysfunction, numbness, upper and lower extremities, lower extremity areflexia | MRI: Unremarkable | N/A | IVIG | Improvement and return of patellar reflexes after IVIG | Miller Fisher syndrome | |||
| Lahiri and Ardila 2020 [32] | 72 | M | Onset | Unspecified | Encephalopathy | N/A | N/A | Not reported | Not reported | COVID-19 presentation | |||
| Lantos et al. 2020 [33] | 36 | M | 4 days | Gait | Partial left cranial nerve III palsy, decreased sensation in lower extremities, areflexia | MRI: Enlargement and enhancement of left cranial nerve III | N/A | IVIG | Improvement after IVIG | Miller Fisher syndrome variant | |||
| Lowery et al. 2020 [34] | 45 | M | 2 weeks | Gait | Left facial and bilateral lower extremity numbness, dysgeusia, dysphagia, quadriparesis, bilateral ptosis, cranial nerve III, IV, and VI weakness, generalized areflexia | MRI: Unremarkable | N/A | IVIG 0.4 g/kg daily (day 1 of ICU admission, then days 6–8) | Improvement, noted 5.5 months after diagnosis | Miller Fisher syndrome, Guillain-Barré syndrome overlap | |||
| Manganotti et al. 2020 [35] | 49 | F | 14 days | Limbs | Bilateral ophthalmoplegia, generalized areflexia, right face hypoesthesia, mild right facial deficit | MRI: Unremarkable |
EMG: Increased distal latency for facial nerve recorded from orbicularis oris and decreased amplitude on right |
IVIG 0.4 g/kg daily for 5 days | Improvement after IVIG | Miller Fisher syndrome variant | |||
| Manganotti et al. [36] | 50 | F | 16 days | Gait, left upper extremity | Opthalmoplegia, generalized areflexia, lower facial deficits, left face hypoesthesia | MRI: Unremarkable | N/A | IVIG 0.4 g/kg daily for 5 days | Resolved, 7 days after IVIG start | Miller Fisher syndrome variant | |||
| Perrin et al. [37] | 64 | M | 13 days | Unspecified | Confusion, agitation, tremor, aphasia, apraxia, pyramidal syndrome, coma, dysautonomia | MRI: FLAIR and DWI white matter hyperintensities in middle cerebellar peduncles, persistent cytotoxic edema on posterior left frontal lobe |
EEG: Global and diffuse slowing EEG2: Bilateral delta organized in bursts or predominant opposite bifrontal diversions with bilateral theta |
Dexamethasone for 5 days; IVIG for 5 days | Improvement with dexamethasone, then relapse, then rapid improvement with IVIG | Para-infectious, cytokine release syndrome | |||
| Perrin et al. [37] | 53 | F | Unclear, immediately after extubation | Unspecified | Confusion, agitation, tremor, aphasia, behavioural alterations, cognitive disturbances | MRI: Unremarkable | EEG: Normal | No specific neurological treatment | Spontaneous and gradual improvement, 7 days after symptom onset | Para-infectious, cytokine release syndrome | |||
| Perrin et al. [37] | 51 | M | Unclear, immediately after extubation | Unspecified | Confusion, agitation, tremor, pyramidal syndrome, behavioural alterations, cognitive disturbances | MRI: FLAIR hyperintensities and microhemorrhages in splenium of corpus callosum | N/A | No specific neurological treatment | Spontaneous and gradual improvement | Para-infectious, cytokine release syndrome | |||
| Perrin et al. [37] | 67 | M | 11 days | Unspecified | Decreased visual acuity, cranial nerve VI palsy, behavioural alterations, pyramidal syndrome | MRI: Unremarkable | N/A | Methylprednisolone 500 mg daily for 3 days | Rapid improvement with methylprednisolone | Para-infectious, cytokine release syndrome | |||
| Povlow and Auerbach [38] | 30 | M | Onset | Limbs, gait | Dysarthria, direction-changing nystagmus horizontally |
CTA: Unremarkable MRI: Unremarkable MRA: Unremarkable |
N/A | No specific neurological treatment | Some improvement by hospital day 10 | COVID-19 presentation | |||
| Sartoretti et al. [39] | 60 | M | 17 days | Unspecified | Vertigo, headache, nystagmus |
CT: Hyperdense right vertebral artery CTA: Right vertebral artery and posterior infereior cerebellar artery (PICA) occlusion MRI: Susceptibility weighted, long-segment vessel occlusion with blooming artifact in right vertebral artery and PICA. Diffusion restriction in cerebellar hemispheres and vermis |
N/A | Aspirin, atorvastatin | Not reported | Ischemic stroke | |||
| Wright et al. 2020 [40] | 79 | M | 8 days | Trunk, gait | Confusion, agitation, ocular flutter, opsoclonus | MRI: Unremarkable | N/A | None | Opsoclonus resolved 17 days after onset | Post-infectious | |||