Table 1.
Clinical summary of the selected cases included in the review which include 28 case reports and 2 limited case series
| No | Article | Age, Gender | Neurological presentation | Investigation results | Treatment | Outcome |
|---|---|---|---|---|---|---|
| 1 | Panariello A, et al. (2020) [14] | 23, male |
Occurred during acute infection before typical COVID-19 symptoms; psychomotor agitation, anxiety, thought disorganization, persecutory delusions, hallucinations and insomnia |
MRI brain did not show significant finding |
Corticosteroid; IVIG |
Clinical conditions are ameliorating to date |
| EEG showed theta activity, unstable, non-reactive to visual stimuli and no significant asymmetries | ||||||
| CSF analysis raised IL-6, no elevated protein and cell counts | ||||||
| Anti-NMDAR antibodies positive in CSF | ||||||
| 2 | Bravo GA, et al. (2020) [15] | 30, female |
Occurred during acute infection before typical COVID-19 symptoms; psychomotor agitation, paranoid ideation, dysarthria, visual hallucinations and seizure |
MRI brain showed hyperintensities in the left hippocampus |
Corticosteroid; IVIG; surgical removal of ovarian teratoma |
Incomplete recovery; with cognitive sequelae and memory disorder |
| EEG showed epileptic discharges in the left frontotemporal region | ||||||
| Repeated EEG showed delta brush pattern together with spike-and-wave discharges in anterior regions | ||||||
| CSF showed high protein and pleocytosis (lymphocyte predominance) | ||||||
| Anti-NMDAR antibodies positive in serum and CSF | ||||||
| 3 | Monti G, et al. (2021) [16] | 50, male |
Occurred during acute infection with no fever or respiratory symptoms; acute psychosis, later developed focal motor seizures and progressed into refractory status epilepticus |
Serial MRI brain was normal |
IVIG; PLEX; corticosteroid |
Complete recovery |
| EEG showed diffuse delta activity (delta brush pattern) | ||||||
| CSF analysis raised IL-6 (also in serum), mild elevated protein and mild pleocytosis | ||||||
| Anti-NMDAR antibodies positive in CSF | ||||||
| 4 | Allahyari F, et al. (2021) [17] | 18, female |
Occurred before acute infection; lack of concentration, anhedonia and seizure |
CT brain showed brain oedema |
Corticosteroids; IVIG |
Complete recovery |
| MRI brain normal | ||||||
| EEG not available | ||||||
| CSF showed high protein and pleocytosis (lymphocyte predominance) | ||||||
| Anti-NMDAR antibody positive in CSF | ||||||
| 5 | Guilmot A, et al. (2021) [20] | 80, male |
Occurred during acute infection with mild respiratory symptoms; short-term memory disturbances, visual hallucinations, anxiety and seizure |
MRI brain normal | Corticosteroid PLEX | Complete recovery |
| EEG show generalized slowing | ||||||
| CSF analysis elevated protein and positive oligoclonal band with normal cell counts | ||||||
| Anti CASPR2 antibody was positive in CSF and serum | ||||||
| 6 | Gaughan M, et al. (2021) [23] | 16, female |
Occurred during acute infection with no fever or respiratory symptoms; hallucinations and ritualistic behaviours, subsequently severe encephalopathy with akinetic mutism. She then developed bilateral limb rigidity with subtle high frequency tremor |
MRI brain showed 2 tiny punctate T2/FLAIR hyperintensities in the centrum semi-ovale bilaterally, with no diffusion restriction or contrast enhancement |
IVIG; corticosteroid |
Complete recovery |
| CSF analysis normal | ||||||
| EEG delta slowing, more prominent in the right hemisphere posteriorly | ||||||
| Anti-GAD antibody level was positive in serum but negative in CSF | ||||||
| 7 | Ayuso LL, et al. (2020) [24] | 71, female |
Occurred after acute infection; unsteadiness, dizziness and severe truncal ataxia |
MRI brain showed hyperintense lesions in the caudal vermis and right flocculus, and contrast enhancement was observed in the floor of the fourth ventricle | Corticosteroid | Almost complete recovery with mild unsteadiness |
| EEG was normal | ||||||
| CSF was normal | ||||||
| Anti-GD1a IgG antibodies positive in serum | ||||||
| 8 | Yousuf F, et al. (2021) [30] | 60, male |
Occurred after acute infection; Altered mental status, memory impairment and aphasia |
PET scan of brain showed abnormal mixed brain hypometabolism and hypermetabolism (suggesting an early pattern of autoimmune encephalitis) | IVIG | Almost complete recovery |
| 48 h of video EEG showed severe diffuse encephalopathy, no seizures or epileptiform discharges | ||||||
| CSF analysis elevated protein | ||||||
| Autoantibody panel negative | ||||||
| 9 | Grimaldi S, et al. (2020) [31] | 72, male |
Occurred during acute infection before typical COVID-19 symptoms; subacute cerebellar syndrome and myoclonus |
MRI brain normal |
IVIG corticosteroid |
Complete recovery |
| PET scan of brain showed a diffuse pattern compatible with encephalitis and cerebellitis | ||||||
| EEG showed symmetric diffuse background slowing and reactive to stimulation without interictal paroxysm | ||||||
| CSF analysis no elevated protein and cell counts | ||||||
| High titres of autoantibodies directed against the nuclei of Purkinje cells, striatal and hippocampal neurons | ||||||
| 10 | McAlpine LS, et al. (2021) [32] | 60, male |
Occurred during acute infection before typical COVID-19 symptoms; confusion and cognitive decline concerning for encephalopathy |
MRI brain showed scattered foci of FLAIR hyperintensity in the periventricular and subcortical white matter (likely sequelae of chronic small vessel disease) | None | Ongoing improvement |
| EEG showed mild to moderate generalized slowing without seizures or epileptiform patterns | ||||||
| CSF analysis not available | ||||||
| Autoantibody panel not available | ||||||
| 11 | Oosthuizen K, et al. (2021) [33] | 52, male |
Occurred during acute infection with no fever or respiratory symptoms; progressive gait instability with other cerebellar signs, including nystagmus, dysarthria and truncal ataxia |
MRI brain showed features consistent with brainstem encephalitis | Corticosteroid | Almost complete walking independently with dysarthria, broad-based gait |
| EEG not available | ||||||
| CSF analysis revealed pleocytosis with normal protein. PCR for SARS-CoV-2 RNA was positive | ||||||
| Anti-amphiphysin antibody positive in the serum | ||||||
| 12 | Zambreanu L, et al. (2021) [36] | 66, female |
Occurred during acute infection with mild respiratory symptoms; confusion, memory deficits and seizure |
MRI brain showed T2 hyperintensities in limbic lobes, upper pons and medial thalami, without gadolinium enhancement (consistent with limbic encephalitis) |
Corticosteroid IVIG |
Incomplete recovery; ongoing cognitive impairment |
| EEG not available | ||||||
| CSF analysis elevated protein | ||||||
| Autoantibody panel negative | ||||||
| 13 | Pilotto A, et al. (2020) [37] | 68, male |
Occurred during acute infection with severe respiratory symptoms; altered mental state, status epilepticus and dysarthria |
MRI consistent with limbic encephalitis | None | Complete recovery |
| EEG was abnormal, but no detail | ||||||
| CSF analysis elevated protein and pleocytosis | ||||||
| Autoantibody panel negative | ||||||
| 76, female |
Occurred during acute infection with severe respiratory symptoms; altered mental state, and aphasia |
MRI consistent with limbic encephalitis | Corticosteroid |
Incomplete recovery; unable to perform all previous activities |
||
| EEG was abnormal, but no detail | ||||||
| CSF analysis elevated protein | ||||||
| Autoantibody panel negative | ||||||
| 14 | Hamill A (2021) [38] | 59, female |
Occurred during acute infection before typical COVID-19 symptoms; altered mental status and syncopal attack |
MRI brain showed diffuse abnormal hyperintensities over right hippocampus (consistent with limbic encephalitis) |
Not available | Still in ICU |
| EEG normal | ||||||
| CSF analysis elevated protein | ||||||
| Autoantibody panel not available | ||||||
| 15 | Chenna V, et al. (2021) [39] | 58, male |
Occurred after acute infection; altered sensorium (during his admission for COVID-19 and was intubated) |
MRI brain showed bilateral cerebellar, parietooccipital hyperintensities on T2/FLAIR mode | IVIG | Complete recovery, able to walk |
| EEG not available | ||||||
| CSF analysis normal | ||||||
| Autoantibody panel not available | ||||||
| 16 | Khoo A, et al. (2020) [40] | 65, female |
Occurred after acute infection; generalized myoclonus, ocular flutter with convergence spasm and acquired hyperekplexia |
MRI brain normal | Corticosteroid |
Incomplete recovery; walking with stick ongoing fine myoclonus |
| EEG not available | ||||||
| CSF analysis normal | ||||||
| Autoantibody panel negative | ||||||
| 17 | Dono F, et al. (2021) [41] | 81, male |
Occurred after acute infection; altered mental status, fever, then reduced consciousness with recurrent myoclonic jerk |
MRI brain showed multiple hyperintense areas in T2-FLAIR and axial DWI in the bilateral parietal cortex, left temporal cortex and right cingulate cortex with no contrast enhancement after gadolinium injection |
Corticosteroids; IVIG |
Minimal recovery; myoclonic jerk stops, then the patient succumbs to hospital acquired infection |
| EEG showed lateralized periodic discharges plus superimposed fast activity over the left frontocentrotemporal regions | ||||||
| CSF showed high protein and pleocytosis (lymphocyte predominance) | ||||||
| Autoimmune panel negative | ||||||
| 18 | Pizzanelli C, et al. (2021) [42] | 74, female |
Occurred after acute infection; subacute confusion and focal motor seizures with impaired awareness |
MRI brain showed bilateral T2/FLAIR hyperintensities in both hippocampi (consistent with limbic encephalitis) |
Corticosteroid; antiseizure medications |
Almost complete recovery with slight verbal deficits |
| EEG showed focal seizure with onset in left temporal lobe | ||||||
| CSF analysis elevated protein | ||||||
| Autoantibody panel negative | ||||||
| 19 | Hosseini AA, et al. (2020) [43] | 79, female |
Occurred during acute infection with fever and no respiratory symptoms; acute confusion, dysphasia and seizure |
MRI brain showed partial diffusion restriction in limbic system (suggestive of limbic encephalitis) | Antiseizure medications | Poor recovery with impaired verbal fluency, delayed recall memory |
| EEG not available | ||||||
| CSF analysis was normal | ||||||
| Autoantibody panel not available | ||||||
| 20 | Zuhorn F, et al. (2020) [44] | 54, male |
Occurred during acute infection with no fever or respiratory symptoms; altered mental state, disorientated and stupor prior to respiratory failure and intubated |
MRI brain showed signal alterations at the claustrum/external capsule region, showing reduced diffusion | None | Almost complete recovery with mild cognitive impairment |
| EEG not available | ||||||
| CSF analysis revealed pleocytosis with normal protein | ||||||
| Autoantibody panel not available | ||||||
| 21 | Bhagat, et al. (2021) [45] | 54, male |
Occurred during acute infection before typical COVID-19 symptoms; headache, loss of consciousness and seizure |
MRI brain showed increased signal in DWI without ADC correlation in the posterior aspect of right medial temporal lobe and para-hippocampal gyrus with associated T2-weighted-FLAIR signal hyperintensity | Antiseizure medications | Complete recovery |
| EEG showed lateralized periodic discharges and focal delta slowing over right posterior quadrant | ||||||
| CSF analysis normal | ||||||
| Autoantibody panel negative | ||||||
| 22 | McAlpine LS, et al. (2021) [46] | 30, male |
Occurred during acute infection after typical COVID-19 symptoms; bizarre delusion, sleep disturbance and hallucination |
MRI brain normal | IVIG | Complete recovery |
| EEG was normal | ||||||
| CSF analysis was normal | ||||||
| Anti-neural autoantibodies test on CSF revealed a novel immunostaining pattern | ||||||
| 23 | Ayatollahi P, et al. (2021) [47] | 18, female |
Occurred during acute infection before typical COVID-19 symptoms; Drowsiness, confusion and seizure |
MRI brain showed signal hyperintensities on FLAIR and T2-weighted sequences in the claustrum bilaterally and extended to the external capsules and anterior insular cortex, sparring mesial temporal structures |
Corticosteroid; antiseizure medications |
Almost complete recovery with persistent recent memory deficit |
| EEG showed intermittent non-epileptiform abnormalities over the both frontocentrotemporal regions | ||||||
| CSF analysis no elevated protein and cell counts | ||||||
| Autoantibody panel negative | ||||||
| Paediatric | ||||||
| 24 | Burr T, et al. (2021) [18] | 23-month girl |
Occurred during acute infection with fever and no respiratory symptoms; communication and movement disorders, multiple seizures and gradual worsening of encephalopathy |
MRI brain was normal | IVIG | Complete recovery |
| EEG not available | ||||||
| CSF analysis no elevated protein and cell counts | ||||||
| Anti-NMDAR antibodies positive in serum and CSF | ||||||
| 25 | Sarigecili E, et al. (2021) [19] | 7-year-old boy |
Occurred during acute infection with no fever or respiratory symptoms; unsteady gait, then progressed to choreiform movements, tongue protrusion, bruxism and lip smacking |
MRI brain was normal |
IVIG corticosteroid |
Almost complete recovery with mild ataxia |
| Awake and sleep EEGs were encephalopathic with widespread delta waves | ||||||
| CSF analysis no elevated protein and cell counts | ||||||
| Anti-NMDAR antibody positive in CSF | ||||||
| 26 | Vraka K, et al. (2021) [21] | 13-month girl |
Occurred during acute infection before typical COVID-19 symptoms; impaired consciousness, seizures with decorticated posturing |
MRI brain showed bilateral widespread high signal abnormalities over white matter, including the splenium of the corpus callosum with associated diffusion restriction and high signal in the thalami and pons | Corticosteroid | Complete recovery |
| EEG showed diffuse slow-wave background activity (encephalopathy), but no epileptiform discharge | ||||||
| CSF analysis not available | ||||||
| Anti-MOG antibody detected in serum | ||||||
| 10-year-old girl |
Occurred during acute infection with fever and no respiratory symptoms; headache, fluctuating sensorium and right-hand weakness |
MRI brain showed asymmetric bilateral high-signal lesions in the basal ganglia and the subcortical white matter in the frontal and temporal lobes, with involvement of the left internal capsule and left hippocampus | Not available |
Incomplete recovery; neglect right upper limb impairment of verbal memory |
||
| EEG normal | ||||||
| CSF analysis was normal | ||||||
| Autoantibody panel negative | ||||||
| 27 | Ahsan N, et al. (2021) [22] | 7-year-old girl |
Occurred during acute infection with fever and no respiratory symptoms; aphasia, encephalopathy, status epilepticus and prolonged Todd’s paralysis |
MRI brain revealed peri Rolandic and posterior parietal lobe restricted diffusion and cortical oedema |
Antiseizure medications; IVIG |
Almost complete recovery with mild dysarthria |
| EEG showed cerebral slowing with left focal slowing | ||||||
| CSF analysis not available | ||||||
| Anti-MOG antibody detected in serum | ||||||
| 28 | McLendon LA, et al. (2021) [26] | 17-month girl |
Occurred during acute infection before typical COVID-19 symptoms; upper limb weakness, gait disturbance and truncal ataxia |
MRI brain showed multifocal hyperintense T2-FLAIR signals in bilateral subcortical and periventricular white matter without contrast enhancement |
IVIG corticosteroid |
Complete recovery |
| EEG showed diffuse slowing consistent with encephalopathy but no seizures or epileptiform activity | ||||||
| CSF analysis not available | ||||||
| Autoantibody panel not available | ||||||
ADC apparent diffusion coefficient, CASPR2 contactin-associated protein-like-2, CSF cerebral spinal fluid, DWC diffusion weighted imaging, EEG electroencephalogram, FLAIR fluid-attenuated inversion recovery, GAD glutamic acid decarboxylase, IL-6 interleukin-6, IVIG intravenous immunoglobulin G, MOG myelin oligodendrocyte glycoprotein, MRI magnetic resonance imaging, NMADR N-methyl-D-aspartate-receptor, PCR polymerase chain reaction, PET positron emission tomography, PLEX plasma exchange, RNA ribonucleic acid, T2 T2-weighted image