Figure 1
Prisma flowchart for a systematic review of articles on new-onset movement disorders and COVID-19 from PubMed database on January 25, 2021. Search criteria used: “COVID-19” OR “SARS-CoV-2” OR “Coronavirus Disease 2019” OR “2019 n-CoV” OR “2019 Novel Coronavirus” AND (“movement disorders” OR “myoclonus” OR “ataxia” OR “parkinsonism” OR “Parkinson’s disease” OR “chorea” OR “dystonia” OR “myoclonus” OR “catatonia” OR “tremor”).
Table 1
Comprehensive description of COVID-19 cases presenting with movement disorders phenomenology.
| AUTHORS, YEAR, COUNTRY, STUDY DESIGN | CLINICAL SCENARIO, CASE COUNT, METHOD, SEVERITY | MOV. DISORDERS PRESENTATION | NEUROIMAGING | CSF OR RELEVANT LAB STUDIES | NEUROPHYSIOLOGICAL STUDIES | TREATMENT |
|---|---|---|---|---|---|---|
| Romero-Sánchez et al., [3], Spain, Retr., Obs., | Hospital setting, 6 cases, RT-qPCR or serology | 6 cases: hyperkinetic mov.. 3 patients w/ mostly myoc. tremor and 3 w/ tardive synd. w/ oromandibular dyskinesia and tremor (related to neuroleptics) | N/A | N/A | N/A | N/A |
| Studart-Neto et al., [4], Brazil, Retr., Obs. | Hospital setting, 6 cases, RT-qPCR, 2 inpatient, 4 ICU – mechanical ventilation | 6 cases: hyperkinetic mov. (myoc.); 4 of those w/ encephalopathy and one w/ a cerebrovascular disorder | N/A | N/A | N/A | N/A |
| Faber et al., [10], Brazil, Case report | Hospital setting, 1 case, RT-qPCR, Inpatient | Anosmia and acute levodopa-responsive parkinsonism | FDG-PET: Normal glucosemetab. in MRI (3T), normal neuromelanin and nigrosome1 imaging; TRODAT-1 SPECT: Nigrostriatal denervation | Unremarkable | N/A | levodopa-responsive |
| Méndez-Guerrero et al., [11], Spain, Case report | Hospital setting, 1 case, RT-qPCR, ICU w/ mechanical ventilation | Hyposmia, generalized rest and postural myoc., fluctuating consciousness, opsoclonus, and an asymmetric parkinsonian synd. | DaT-SPECT: Bilat. decrease in presynaptic dopamine uptake asymmetrically involving both putamina; CT: unremarkable MRI: unremarkable | Unremarkable | EEG: diffuse mild and reactive slowing | Levetiracetam, not-responsive to apomorphine |
| Piscitelli et al. [12] Italy, Case report | Hospital setting, 1 case, RT-qPCR, Inpatient | Functional tremor w/ entrainment phenomenon and distractibility | Normal brain and spine MRI | N/A | SSEP: normal in legs | Supportive |
| Mas Serrano et al., [13], Spain, Case report | Hospital setting, 2 cases, RT-qPCR, Inpatient | Serotonergic synd. (w/ myoc.) due to association of lopinavir/ritonavir and psychotropic drugs (duloxetine, lithium, risperidone, haloperidol, morphine) | Case 1: normal MRI Case 2: normal CT | High levels of CPK. | EEG w/ encephalopathic findings (both cases) | Case 1: cyproheptadine Case 2: clonazepam |
| Rábano-Suárez et al., [14], Spain, Case series | Hospital setting, 3 cases (2 w/ a typical clinical scenario and lung CT scan, 1 RT-qPCR), 1 ICU and mechanical ventilation, 2 inpatient | Generalized myoc. and hypersomnia | Case 1, 3: normal MRI, Case 2: normal head CT; | Case 1: Unremarkable Case 2, 3: not reported | EEG: mild background slowing (3) | 3 cases w/ CS (MP), 2 cases w/ clonazepam and levetiracetam, 1 case w/ valproic acid |
| Cuhna et al. [15], France, Case series | Hospital, 5 cases, RT-qPCR, ICU w/ mechanical ventilation | 3 subjects w/ act. and postural tremor in UL, one patient w/ hemicorporal act. tremor, one w/ jerky tremor; All w/ mild motor deficit | MRI: microbleeds (4), unilateral nigrossomal abnormality (1) SPECT: frontotemporal hypoperfusion (1) DAT-Scans: normal (4). | N/A | EEG/ENMG: cortical/subcortical myoc. (2), short myoclonic bursts. | N/A |
| Paterson et al., [16], United Kingdom, Retr., Obs. | Hospital, 2 cases RT-qPCR, Inpatient | Case 1: encephalopathy case w/ act. tremor and LL ataxia; Case 2: opsoclonus, stimulus sensitive myoc., hyperekplexia, and convergence spasm | Case 1: neuroimaging within normal limits; Case 2: normal Brain MRI; | Case 2: unremarkable | Case 2: EEG: unremarkable | Case 1: supportive; Case 2: steroids, levetiracetam, clonazepam |
| Chaumont et al. [17], France, Case series | Hospital 4 cases, RT-qPCR, ICU w/ mechanical ventilation | Mixed central and peripheral features: encephalopathy (4), ataxia (4), postural and act. myoc. (4), and polyneuropathy (4) | MRI: 3 cases w/ normal brain imaging, one w/ recent stroke in MCA territory; | Mildly elevated protein levels (2) | EEG: background slowing (3); normal (1). ENMG: motor demyelinating polyradiculoneuropathy (3) or diffuse lower motor neuron involvement (1) | IVIg 0.4 g/kg (4), steroids (3) |
| Dijkstra et al. [18], Belgium, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Action-induced myoclonic jerks, stuttering speech hyposmia, transient ocular flutter, gait ataxia, attention and memory deficits, hypervigilance, and insomnia. | Normal brain and spinal MRI PET-CT: neg. screening for neoplasia. | Unremarkable, neg. autoimmune and paraneoplastic antineuronal Abs | N/A | CS and IVIg |
| Gutiérrez-Ortiz et al. [19], Spain, Case report | Hospital, 2 cases, RT-qPCR, Inpatient | Anosmia, ageusia, right internuclear ophthalmoparesis, right fascicular oculomotor palsy, ataxia, areflexia, (Miller-Fisher synd.) | Head CT: normal (2) | Pos. GD1b-IgG (1), albuminocytologic dissociation (2), mildly elevated CSF protein levels. | N/A | Case 1: IVIg Case 2: supportive, spontaneous recovery |
| Lantos et al., [20], USA, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Progressive ophthalmoparesis (left CN III and Bilat. CN VI palsies), ataxia, and hyporeflexia (Miller-Fisher synd.) | MRI: prominent enhancement w/ gadolinium, T2 hyperintense left oculomotor nerve (CN III) | Neg. GD1b-IgG, | N/A | IVIg |
| Balestrino et al., [21], Italy, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Asthenia, gait ataxia, balance impairment, confusion, and drowsiness | Head CT: Unremarkable | N/A | EEG: focal delta slowing, sporadic spikes | Lopinavir/ritonavir, chloroquine, CS and levofloxacin |
| Mao et al. [22], China, Retr., Obs. | Hospital, 1 case, RT-qPCR, ICU w/ mechanical ventilation | Ataxia and severe COVID-19 infection | N/A | N/A | N/A | N/A |
| Fadakar et al., [23], Iran, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Myalgia, progressive vertigo, headache, dysarthria, and cerebellar ataxia. | MRI: edema of cerebellar hemispheres and vermis, leptomeningeal enhancement. | Mild lymphocytic pleocytosis, elevated protein, and lactate dehydrogenase and pos. for SARS-CoV-2, Neg. antineuronal Abs panel | N/A | Lopinavir/ritonavir |
| Xiong et al. [24], China, Retr., Obs. | Hospital, 2 cases, RT-qPCR Inpatient | Tics/tremor (functional?). Case 1: 8 days after initial symptoms Case 2: 41 days after initial symptoms | N/A | N/A | N/A | N/A |
| Klein et al. [25], USA, Case report | Hospital, 1 case, diagnostic method not available, Inpatient | Bilat. intention tremor and wide-based gait (ataxia) | Head CT and angioCT: no abnormalities; Brain MRI: no acute findings | N/A | N/A | Propranolol |
| Cohen et al., [26], Israel, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Hypomimia and hypophonia. Cogwheel rigidity in neck, right arm, left arm, Asymmetric bradykinesia, no tremor. Slow gait, no right arm swing. No postural instability. | MRI: unremarkable ¹⁸F-DOPA PET: asymmetrically decreased uptake in putamens, more apparent on the left side. | Unremarkable, Neg. for GABA type B receptors, NMDAR, CASPR2, AMPA receptor type 1, AMPA receptor type 2, and LGI1. | EEG: unremarkable | Low-dose pramipexol |
| Sanguinetti & Ramdhani., [27], USA, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Appendicular and axial ataxia, act. myoc., act. tremor, Spontaneous horizontal and vertical eye oscillations (opsoclonus-myoclonus-ataxia synd.) | Brain MRI- normal | N/A | N/A | CS and IVIG (400mg/kg/d, 5d) |
| Ros-Castelló et al. [28], Spain, Case report | Hospital, 1 case, RT-qPCR ICU w/ mechanical ventilation | Myoc. in UL and neg. myoc. in LL, leading to falls, delayed onset | Brain MRI: cortical and brainstem ischemic lesions (hyperintensities in DWI and FLAIR) | N/A | N/A | Low-dose clonazepam |
| Wright et al., [29], New Zealand, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Saccadic oscillations (ocular flutter and opsoclonus) and gait ataxia, w/ no myoc., encephalopathy | Brain MRI: chronic white matter changes | N/A | N/A | Supportive, deceased |
| Muccioli et al. [30], Italy, Case report | Hospital, 1 case, RT-qPCR, ICU w/ mechanical ventilation | Multifocal myoc. elicited by act. and tactile stim., predominant in the right proximal LL | Brain MRI: chronic white matter changes | Mild pleocytosis (5 cells/μL), elevated protein (75mg/dL), neg. SARS-CoV2 PCR, elevated IL-8. Neg. antineuronal Abs. | EEG: normal; PolyEMG: multifocal positive myoc. w/ a burst of 140 -220 milliseconds EEG-EMG back-averaging: no jerk-locked discharges. | Levetiracetam and clonazepam |
| Borroni et al., [31], Italy, Case series | Hospital, 2 cases, RT-qPCR, Inpatient | Diaphragmatic myoc. (jerky contractions of abdominal muscles, diaphragm); | Case 1: Brain MRI: normal Case 2: Head CT: normal; | Case 1: mild pleocytosis (8 cells/mm3). Case 2: lymphocytosis (24 cell/mm3), increased protein (46 mg/dL). | Case 1: EMG: 3 Hz synchronous discharges EEG: normal; SSEP: normal Case 2: EEG: synchronous and asynchronous LPDs (w/ myoc.); | Case 1: low dose clonazepam Case 2: levetiracetam |
| Schellekens et al., [32], Netherlands, Case report | Outpatient, 1 case, RT-qPCR, Inpatient | Generalized myoc. jerks of trunk, face, and limbs, particularly UL, at rest, worsened w/ posture and action. Cerebellar ataxia. | Brain MRI: unremarkable. | Normal routine profile; neg. for Paraneoplastic antineuronal Abs. | N/A | Levetiracetam |
| Anand et al., [33], USA, Case series | Hospital, 8 cases, RT-qPCR, 7 ICU w/ mechanical ventilation, 1 inpatient | Stimulus- or action-induced myoc. (7) and spontaneous myoc. (1). Generalized (5) and UL myoc. (3). | Head CTs: unremarkable (5) MRI: unspecific temporal T2 hyperintensity (1) MRI: Diffuse pachymeningeal enhancement (1) | Normal protein (2), High protein levels (83 mg/dL) (1), normal cell count (3) | EEG: Bifrontal sharp waves (1), background slowing (2) | Levetiracetam (3), Ketamine (1), dexmedetomidine (5), midazolam (1), lorazepam (3), primidone (1), clonazepam (1), valproic acid (3) |
| Grimaldi et al., [34], France, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Act. tremor, cerebellar ataxia, stimulus-sensitive and spontaneous diffuse myoc. | Brain MRI: Unremarkable ¹⁸F-FDG PET: Putaminal and cerebellum hypermetab., diffuse cortical hypometab. | Normal cell count, mildly elevated protein level (49 mg/dL), neg. RT-qPCR, and neg. OCBs. Immunostaining: Abs against nuclei of Purkinje, striatal and hippocampal neurons. | EEG: background slowing, reactive to stimulation (1) | IVIg, IV CS, Low-dose clonazepam |
| Byrnes et al., [35], USA, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Homeless and drug-addicted. Encephalopathy and choreiform mov. | Brain MRI: Multiple focal enhancing lesions: Bilat. putamen and cerebellum. Several cortical and subcortical lesions, hippocampus, right basal ganglia. | Mildly lymphocytic pleocytosis and increased myelin basic protein. | N/A | IV CS, IVIg, oral CS Chorea improved on day 15, w/ an immediate resolution on day 22. |
| Kopscik et al. [36], USA, Case report | Hospital, 1 case, RT-qPCR and serology, Inpatient | Multiple cranial nerve abnormalities, dysmetria, sensory ataxia, and absent LL reflexes | Brain MRI: unremarkable | Anti-GQ1b IgG Abs (1:100), w/ lymphocytic predominance, normal protein | N/A | Convalescent plasma, tocilizumab, and intravenous immunoglobulin. |
| Fernández-Domínguez et al., [37], Spain, Case report | Hospital, 1 case, RT-qPCR and serology, Inpatient | LL areflexia, sensory gait ataxia. | Brain MRI: unremarkable | Increased protein level (110 mg/dl) Normal cell count. Neg. antiganglioside Abs. SARS-CoV-2 neg.. | EMG: slight F-wave delay in ULs. Visual evoked potential: unremarkable | IVIg, w/ improv.. |
| Dinkin et al., [38], USA, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Partial unilat. oculomotor palsy, Bilat. abducens palsies. LL hyporeflexia and hypesthesia, and gait ataxia. | Brain MRI: enhancement, T2-hyperintensity, and enlargement of oculomotor nerve | Ganglioside Abs: neg. | N/A | IVIg, w/ improv.. |
| Perrin et al., [39], France, Retr., Obs. | Hospital, 5 cases, RT-qPCR, ICU, 2 w/ mechanical ventilation | Confusion (n = 5), tremor (n = 5), cerebellar ataxia (n = 4), behavioral alterations (n = 5), aphasia (n = 4), pyramidal synd. (n = 4), coma (n = 2), cranial nerve palsy (n = 1), | Brain MRI: acute leukoencephalitis (cases 1, 2, and 4), microbleeds in the corpus callosum (1); cytotoxic edema mimicking stroke (case 2), and normal results (cases 3 and 5); | SARS-CoV-2 PCR: neg.. CSF/serum albumin index increased (3), Normal cell count (5), Absent IgG intrathecal synthesis (5), OCBs (3), Antineuronal Abs absent (5). | Case 1: EEG: asymmetric slow-wave spikes and occipital focus Case 2: EEG: slow Bilat. delta bursts or predominant opposite bifrontal diversions w/ Bilat. 5–6 Hz theta Case 3: normal | Case 1: CS (DM) Case 2: CS (DM) + IVIg w/ improv. Case 3, 4: spontaneous recovery Case 3: CS (DM + MP) w/ improv. |
| Hayashi et al., [40], Japan, Case report | Hospital, 1 case, RT-qPCR, ICU | Marked dysmetria and mild ataxic gait | Brain MRI: hyperintensity in splenium of corpus callosum on DWI [mild encephalitis/encephalopathy w/ a reversible splenial lesion (MERS)] | N/A | N/A | Spontaneous recovery of neurologic symptoms |
| Khoo et al., [41], England, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Myoc., ocular flutter, convergence spasm, hyperekplexia, confusion | Brain MRI: normal | Unremarkable. Neg. viral PCR panel. Neg. SARS-CoV-2 PCR. Neg. antineuronal Abs. | EEG: normal | Levetiracetam, clonazepam w/ partial improv. in myoc. and hyperekplexia. CS (MP and prednisone); all neurological symptoms improved |
| Pilotto et al., [42], Italy, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Irritability, confusion, and asthenia. Severe akinetic synd. and mutism; Frontal release signs, nuchal rigidity. | Head CT: unremarkable Brain MRI: unremarkable | Lymphocytic pleocytosis (18/uL), increased protein (69.6 mg/dL). Neg. viral panel. Neg. SARS-CoV-2 PCR. Neg. OCBs and antineuronal Abs. | EEG: Generalized background slowing, decreased reactivity | CS (MP 1 g/day (five days), prednisone, w/ improv. |
| Delorme et al., [43], France, Case series | Hospital, 2 cases, RT-qPCR, Inpatient | Case 1: psychomotor agitation, cognitive/behavioral frontal synd., UL myoc., cerebellar ataxia. Case 2: psychomotor agitation, anxiety, depressed mood, dysexecutive and cerebellar synd. (hypotonia, gait ataxia, dysmetria, dysarthria, nystagmus) | Brain FDG-PET: Bilat. prefrontal and left parieto-temporal hypometab., hypermetab. in vermis Brain FDG-PET: bilat. Orbitofrontal hypometab., Bilat. Hypermetab. in striatum and vermis. | CSF 1: Mild pleocytosis (6 cells/mm3), normal protein. CSF 2: 0 cells/m3, normal protein. | EEG: normal in both cases | 1: IVIg 2 g/kg. Gradual improv., up to 6 weeks long. 2: CS (2 mg/kg/day for 3 days). Improved cerebellar symptoms. Antidepressants (paroxetine and mirtazapine) |
| Caan et al., [44], USA, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Hallucinations, delusions, apathy, muscle rigidity and diaphoresis, catatonia. | Brain MRI: unremarkable | Normal cell count, protein, and gluc. level. | N/A | Lorazepam with partial recovery |
| Pilotto et al., [45], Italy, Longitudinal, multicentric | Hospital, 25 encephalitis cases, 1 w/ a mov. disorder, RT-qPCR, Inpatient | Altered mental status w/ extrapyramidal synd. (parkinsonian synd.) | Brain MRI: frontal T2 hyperintensities | Cels.: 4/mm3; mildly elevated protein; | N/A | N/A |
| Povlow et al., [46], USA, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Nausea, dysarthria, dysmetria, dysdiadochokinesia, mod. appendicular ataxia, unable to stand unassisted. | Brain MRI: unremarkable | Mild lymphocytic pleocytosis (7 cells/mm3), normal protein, neg. meningitis/encephalitis panel; neg. OCBs. | N/A | Spontaneous partial recovery |
| Franke et al., [47], Germany, Retrospective case series | Hospital, 8 cases w/ a mov. disorder, RT-qPCR, ICU – respiratory status not available | Case 1: nystagmus, orofacial myoc., delirium Case 2: nystagmus, generalized stimulus-sensitive myoc. Case 3: unilat. stimulus-sensitive myoc. Case 4: unilat. orofacial myoc. Case 5: Delirium, myoc., epileptic seizures Case 6: unilat. faciobrachial myoc., multifocal strokes Case 7: Oculomotor paresis, transient generalized myoc., prolonged awakening Case 8: Asym. Dystonia (UL), delirium | Head CT: Normal (4); PET-FDG: increased metab. in basal ganglia, limbic system, and cerebellum (1). Brain MRI: Marked fornix edema (1), right middle cerebral artery (MCA) ischemia (1) | N/A | N/A | N/A |
| Fernando et al., [48], Philippines, Case report | Hospital, 1 case, RT-qPCR, Inpatient | Bilat., asynchronous, irregular myoc. (UL, LL) | Brain MRI: unremarkable | N/A | N/A | Resolution 2 weeks after hydroxychloroquine withdraw |
| Deocleciano de Araujo et al., [49], Brazil, Case report | Hospital, 1 case, RT-qPCR, ICU | Disorganized behavior, social withdrawal, reduced motor output, body stiffness, negativism, refusal to feed, weight loss. | Head CT: normal | Protein 55 mg/dL | N/A | Lorazepam, sertraline, Electroconvulsive therapy, resolution after 50 days |
| Emamikhah et al., [50], Iran, Case series | Hospital, 7 cases, Rt-qPCR (5 cases), serology (1 case), clinical (1 case) Inpatient | Myoc. (7), opsoclonus (3), ataxia (7), voice tremor (6). | Head CT: normal (2); Brain MRI: normal (4) | Normal cell count (3), protein (3), gluc. (3). Neg. OCBs (1). | EEG: normal (1). | Clonazepam (6), Levetiracetam (3), Valproate(5), IVIg (5), CS (1) |
| Urrea-Mendoza et al., [51], USA, Case report | Hospital, 1 case, RT-qPCR Inpatient | Opsoclonus, myoc., and ataxia | Brain MRI: normal | N/A | N/A | Clonazepam, valproate (divalproex), steroids |
[i] PET – positron emission tomography; SPECT – Single-photon emission computed tomography, CSF – cerebrospinal fluid, COVID-19 – Coronavirus Disease-2019, RT-qPCR – Quantitative reverse transcription PCR, UL – upper limb; MRI – magnetic resonance imaging, EEG – electroencephalogram; ENMG – electroneuromyography, DAT-Scan: dopamine transporter imaging; LL – lower limb; Abs – antibodies; MCA – middle cerebral artery; DWI – diffusion-weighted imaging; FLAIR – fluid-attenuated inversion recovery; SSEP – somatosensory evoked potential; LPDs – lateralized periodic discharges; DM – dexamethasone, MP – methylprednisolone, IVIg – Intravenous immunoglobulin, ICU – Intensive care unit; Gluc: glucose; Prot: protein; CS: corticosteroids; OCB: oligoclonal bands; Abs: antibodies; N/A: Not available.
Retr. – retrospective, Obs. – observational, Myoc.- myoclonus, Bilat. – bilateral., Unilat. – unilateral, Pos. – positive, Neg. – negative.
Figure 2
COVID-19-associated new-onset movement disorders: case counts in the reported original articles sample. A scale measuring total case counts ranges from 0 to 17 and is visually represented using a color scale ranging from light green to dark blue.
Figure 3
The bar plots’ numbers depict the Bayesian binomial posterior proportion of the described movement disorders or associated phenomenology to the total number of described cases (N = 93) in the reviewed articles. The error bar reflects the error in the posterior estimates. Data source: extracted from individual patients, original articles.
Figure 4
Posterior beta densities from the Bayesian zero-inflated Poisson (ZIP) regressions. The thick segments indicate 50% intervals, while the thinner outer lines indicate 90% intervals. The points in the above plot indicate the posterior medians. Data source: extracted from individual cases, original articles.