Table 3.
Literature review of neurological manifestations associated with SARS-CoV-2 in pediatric patients [[15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53]].
| First author [reference number] | Type of study, Country | Journal | Patients with Severe Neurological Manifestations, Sex, Ages | Severe Neurological Manifestations | EEG/EMG | Neuroimaging CT and/or MRI | Outcome |
|---|---|---|---|---|---|---|---|
| Aghdam et al., 2020 [30] | Case report, Iran | Journal of Pediatric Neurology | n = 1 2-month-old female |
COVID-19: Seizures | EEG: low voltage slow wave activity | Brain CT: a hyperdense center with diameter of 5 mm in left temporal lobe cortex, hemorrhages | Discharged with neurologic baseline |
| Enner et al., 2020 [19] | Clinical letter, United States of America | Pediatric Neurology | n = 1 14-year-old female |
COVID-19: Seizures and apneic episodes | EEG: epileptiform activity | Brain and Spine MRI: normal | Discharged well with no apneic episodes after antiepileptics |
| McAbee et al., 2020 [31] | Correspondence, United States of America |
Pediatric Neurology | n = 1 11-year-old male |
COVID-19: Encephalitis, status epilepticus | EEG: Frontal intermittent delta activity | Head CT: normal | Recovered |
| Frank et al., 2020 [28] | Case report, Brazil | Journal of Tropical Pediatrics | n = 1 15-year-old male |
COVID-19: Guillain-Barré syndrome | EMG: Compatible with GBS, acute motor axonal neuropathy (AMAN type GBS) | Brain MRI: normal | Currently undergoing motor physiotherapy |
| Khalifa et al., 2020 [29] | Case report, Egypt |
Journal of Pediatric Infectious Diseases Society | n = 1 11-year-old male |
COVID-19: Guillain Barre syndrome |
EMG: Compatible with GBS (Acute inflammatory demyelinating polyneuropathy variant) | Brain and Spine MRI: Contrast enhancement of cauda equina nerve roots | Discharged with improved motor activity, but still deep tendon reflexes were hypoactive. |
| Bektaş et al., 2020 [32] | Original article, Turkey | Brain and Development | n = 2 10-year-old male 11-year-old female |
MIS-C: Reversible corpus callosum splenial lesions |
EEG: 1 diffused slowed background activity | Brain MRI: hyperintensity on T2-weighted images in the splenium of the corpus callosum with restricted diffusion | Recovered |
| Abdel-Mannan et al., 2020 [24] | Case series, United Kingdom | JAMA Neurology | n = 4 2 male, 2 female 11.75 years (min-max, 8-15) |
4 MIS-C: 4 encephalopathy, 2 global proximal weakness 1 global flaccid paralysis 1 proximal leg weakness |
EEG: 2 diffuse slow activity, 1 slow activity over the anterior regions EMG: 2 myopathic changes 1 myopathic and neuropathic changes |
Brain MRI: 3 patients have signal changes in the splenium of the corpus callosum on MRI, | No death Encephalopathy resolved. 2 fully ambulant 2 wheelchairs bound |
| de Miranda Henriques-Souza et al., 2020 [33] | Case report, Brazil |
Neuroradiology | n = 1 12-year-old female |
COVID-19: ADEM Acute bilateral progressive weakness |
N/A | Brain MRI: extensive bilateral and symmetric restricted diffusion involving the subcortical and deep white matter. Cervical Spine MRI: longitudinally extensive cervical myelopathy involving both white and gray matter |
Recovered |
| Kaur et al., 2020 [34] | Clinical letter, New Mexico | Pediatric Neurology | n = 1 3-year-old female |
COVID-19: Transverse Myelitis | N/A | Brain & Orbital MRI: normal Spine MRI: swelling of the cervical spinal cord with T2-hyperintense edema involving most of the transverse aspect of the spinal cord, extending from the lower medulla to the midthoracic level. |
Still hospitalized |
| Basirjafari et al., 2020 [35] | Case report, Iran | Journal of Medical Virology | n = 1 9-year-old male |
COVID-19: Subarachnoid hemorrhage Low level of consciousness |
N/A | Brain CT: hyperdensity at basal cisterns, interhemispheric, and bilateral Sylvian fissures in favor of subarachnoid hemorrhage, without intraventricular hemorrhage and hydrocephalus (green arrow); decreased density of white matter in favor of brain edema | Died |
| García-Howard et al., 2020 [20] | Case report, Spain | Frontiers in Pediatrics | n = 1 3-month-old female |
COVID-19: Repeated afebrile seizures | EEG: normal | Brain MRI: normal | Recovered |
| Appavu et al., 2021 [36] | Case report, United States of America | Pediatrics | n = 2 8-year-old female 16-year-old male |
COVID-19: Arteritis and large vessel occlusive stroke 2 acute hemiplegia |
N/A | Case 1, Brain MRI: small completed infarctions in the middle cerebral artery (MCA) territories bilaterally. MRA: proximal left M1 occlusion. Case 2, Brain MRI and MRA: complete left MCA territory infarction, irregularity of left M1 (suggestive of arteritis), and occlusion of left MCA bifurcation. |
No death. Both discharged with need for rehabilitation |
| Bhatta et al., 2020 [21] | Case report, United States of America | Cureus | n = 1 11-year-old male |
COVID-19: seizure | N/A | Head CT: normal | Recovered |
| Bhavsar et al., 2020 [25] | Case report, United States of America | Neurology Clinical Practice | n = 1 16-year-old male |
COVID-19: Encephalitis Low level of consciousness |
EEG: encephalopathy with no seizure findings | Head CT: normal | Recovered |
| Ippolito Bastidas et al., 2020 [18] | Case report, Spain | Neurology Clinical Practice | n = 1 13-year-old female |
COVID-19: Cerebral sinus vein thrombosis Headache, impaired consciousness |
N/A | Head CT: Right occipital intracerebral hemorrhage Brain MRA: bilateral transverse sinus thrombosis with extension to the right sigmoid sinus and internal jugular vein |
Recovered |
| Kihira et al., 2020 [37] | Case report, United States of America | Pediatric Radiology | n = 1 5-year-old male |
COVID-19: Cerebral infarct | N/A | Head CT: large acute right anterior and middle cerebral artery territory infarction and subarachnoid hemorrhage in the left hemisphere. | Death |
| Dugue et al., 2020 [38] | Case report, United States of America | Neurology | n = 1 6-week-old male |
COVID-19: Seizure | EEG: an excess of temporal sharp transients for age and intermittent vertex delta slowing with normal sleep-wake cycling | Brain MRI: normal | Recovered |
| Gaur et al., 2020 [39] | Brief report, United Kingdom | American Journal of Neuroradiology | n = 2 9-year-old male 12-year-old male |
MIS-C & COVID-19: Cytotoxic lesions of corpus callosum Lethargy and headache |
N/A | Case 1, Brain MRI: hyperintense lesion in the splenium of the corpus callosum that exhibited restricted diffusion Case 2, Brain MRI: extensive abnormal T2-weighted hyperintense signal and restricted diffusion in the entire corpus callosum and frontoparietal cerebral white matter |
|
| Abel et al., 2020 [40] | Case report, United States of America | Neurology | n = 1 33-month-old male |
MIS-C: Encephalopathy and bilateral thalamic lesions | İnitial Video EEG: moderate background slowing Control EEG on day 12: mild diffuse slowing |
First Brain MRI: restricted diffusion in the bilateral lateral thalamic nuclei without T2/fluid-attenuated inversion recovery changes. Control MRI on day 15: resolution of thalamic lesions. |
Recovered Discharged with mild residual weakness |
| Verkuil et al., 2020 [41] | Case report, United States of America | The Lancet | n = 1 14-year-old female |
MIS-C: Pseudotumor cerebri Papilledema and abducens nerve paralysis |
N/A | MRI and MRV: revealed abnormalities consistent with increased intracranial pressure | Recovered |
| Swarz et al., 2020 [22] | Correspondence, United States of America | Pediatric Neurology | n = 1 9-year-old female |
COVID-19: Focal status epilepticus | Video EEG: continuous delta slowing throughout the right hemisphere without epileptiform features. | Head CT: normal Brain MRI: normal |
Recovered |
| Mirzaee et al., 2020 [42] | Case report, Iran | Radiology | n = 1 9-year-old male |
COVID-19: Focal cerebral arteriopathy Generalized seizures |
N/A | Brain MRI: acute infarction without microhemorrhages, along with focal irregular narrowing and banding of the proximal M1 segment of the left middle cerebral artery with a slightly reduced distal flow | Discharged with hemiparesis |
| Ahsan et al., 2021 [26] | Case report, United States of America | Clinical Experimental Pediatrics | n = 1 7-year-old female |
COVID-19: Myelin oligodendrocyte glycoprotein antibody encephalitis Status epilepticus |
EEG: cerebral slowing with left focal slowing | Brain MRI: Left perirolandic cortex and posterior parietal lobe cerebral edema | Discharged |
| Sandoval et al., 2021 [23] | Original article, Chile | Journal of Child Neurology | n = 13 8 female, 5 male, 6.5 years (min-max, 1-17) |
8 MIS-C: 6 acute flaccid tetra paresis, 1 seizure, 1 ageusia 5 COVID-19: 1 anosmia and ageusia, 1 febrile seizure, 1 status epilepticus, 1 Guillain Barre Syndrome |
EEG: 2 normal, 1 severely abnormal with slow continuous background activity EMG: 1 moderate acute motor axonal neuropathy (AMAN) |
3 normal CT findings 1 Brain MRI: unenhanced right frontal nodular white matter hypo intensity. 1 Brain and spine MRI: multifocal demyelinating lesions |
No death 2 dysgeusia, 3 no new seizure, 7 complete strength recovery |
| Becker et al., 2021 [43] | Brief report, United States of America | The Journal of Pediatrics | n = 4 3 female, 1 male, 11,25 years (min-max, 6-14) |
4 MIS-C: increased intracranial pressure | 3 EEG: no seizures | 3 Brain CT: normal 1 Brain CT: cerebral edema 1 MRI: normal 1 MRI: papilledema, flattened sinuses |
No death, Discharged with neurologic baseline |
| Saeed et al., 2020 [44] | Case report, Iran | IDCases | n = 1 3-year-old male |
MIS-C: Status epilepticus | N/A | Brain CT on day 1: diffuse cerebral edema Brain MRI: intracerebral hemorrhage in the right occipital lobe. |
Discharged with neurologic baseline |
| Shupper et al., 2020 [45] | Letter to editor, United States of America | Child's Nervous System | n = 1 5-year-old male |
MIS-C: MCA Infarction and Subarachnoid hemorrhage during ECMO | EEG: nonconvulsive status epilepticus | Head CT: a right middle cerebral artery (MCA) infarction, cerebral edema, and diffuse contralateral subarachnoid hemorrhage | Still in ICU |
| Tiwari et al., 2021 [46] | Case report, India |
Lancet Child Adolescent Health | n = 1 9-year-old female |
MIS-C: Acute ischemic stroke | N/A | Head CT: infarct in the genu and adjacent body of the corpus callosum, left basal ganglia and bilateral thalami. CT angiography: multifocal smooth stenosis of intracranial ICAs, right MCA and both A2 segments of ACA. Diffuse narrowing of M2 and M3 segment branches of both MCA. |
No death. Followed up for rehabilitation |
| Regev et al., 2020 [47] | Case report, Israel | The Pediatric Infectious Journal | n = 1 16-year-old male |
MIS-C: central nervous system involvement | N/A | Brain MRI and MRA: diffuse small low signal foci of hemosiderosis in subcortical White matter of both hemispheres and the corpus callosum. | Discharged with improved muscle strength and consciousness |
| De Paulis et al., 2020 [48] | Brief report, Brazil | The Pediatric Infectious Disease Journal | n = 1 4-year-old female |
MIS-C: Confusion and mental somnolence | N/A | Head CT: normal | Recovered |
| Hutchison et al., 2020 [49] | Case report, United States of America |
Psychosomatics | n = 1 14-year-old male |
MIS-C: Delirium | N/A | N/A | Recovered |
| Yousefi et al., 2021 [50] | Case report, Iran |
The Pediatric Infectious Disease Journal | n = 1 9-year-old female |
COVID-19: viral meningitis | N/A | N/A | Recovered |
| Sa et al., 2021 [51] | Case series, United Kingdom |
Neurology, Neuroimmunology and Neuroinflammation | n = 9 5 female, 4 male, 10 years (min-max, 2-15) |
9 MIS-C: 3 altered consciousness 3 acute behavioral changes 2 headache 1 Encephalopathy |
4 patients had EEG and 3 of them were abnormal (2 EEG were compatible with encephalopathy and 1 with seizure) | 4 abnormal neuroimaging 1 acute infarction 1 subtle cortical change 1 splenial and hippocampal changes 1 intraparenchymal hemorrhage and infarction |
1 patient with extensive infarction died, 4 completely recovered, 3 had problems with memory and behavior |
| Akhondian et al., 2021 [52] | Case series, Iran |
International Clinical Neuroscience Journal | n = 5 3 female, 2 male, 7 years (min-max, 5m-12) |
COVID-19: 3 febrile seizures 1 ataxia and drowsiness 1 low level of consciousness and ischemia |
N/A | Brain MRI: 1; consistent with acute infarctions in bifrontal and biparietal lobes 1; hyperintense signals in the brain stem and deep gray matter 1; a small ischemic area in the left centrum semi-oval 1; bilateral scattered subcortical white matter involvement 1; Brain CT scan revealed intraventricular hemorrhage. And had multiple ischemic regions on MRI |
1 died 3 recovered |
| Sánchez-Morales et al., 2021 [27] | Case series, Mexico | Child's Nervous System | n = 10 5 female, 5 male, 13 years (min-max, 2-16) |
3 Guillain Barre Syndrome 2 Optic Neuritis 1 Anti NMDA encephalitis 1 Myositis, 2 Ischemic stroke, 1 infection related ataxia |
3 NCS: AIDP | 2 MRI: optic nerve hyperintensities 2 MRI: Acute Ischemic Stroke 1 CT: normal |
8 recovered 1 Dysphasia, hemicorporeal weakness 1 died |
| Yea et al., 2021 [15] | Preprint, International | Preprint with The Lancet | n = 51 21 female, 30 male 6.6 y (IQR; 3.7–9.7) |
31 patients had only headache 12, Seizure 1, Encephalopathy 3, altered mental status 1 psychosis 1, cranial neuropathy 1, speech impairment |
N/A | 1, Brain and Spine MRI: T2/FLAIR signal hyperintensity in the deep cerebellar hemispheres. Abnormal enhancement of the cauda equina associated with mild thickening of the nerve roots. 1, Brain MRI: diffusion changes in the subcortical white matter |
2 died Others' outcome was not mentioned. |
| LaRovere et al., 2021 [16] | Case series, United States of America | JAMA Neurology | n = 43 16 female, 27 male 12 years (min-maz, 7-15) |
15, Severe encephalopathy (8 MIS-C) 12, Ischemic or hemorrhagic stroke (3 MIS-C) 8, Acute CNS infection or ADEM (6 MIS-C) 4, Acute fulminant cerebral edema (2 MIS-C) 4, Gullian Barré Syndrome (1 MIS-C) |
N/A | Brain CT: 23 Brain MRI:26 5 patients with encephalopathy had brain MRI with abnormal signal intensity and restricted diffusion in corpus callosum and periventricular white matter. 3 fulminant cerebral edema with uncal/tonsillar herniation on imaging (MRI/CT) |
n = 15; Discharged home n = 17; new CNS deficits required rehabilitation n = 11; died |
| Lindan et al., 2020 [17] | Case series, International | The Lancet Child & Adolescent Health | n = 38 18 female, 20 male |
16, ADEM-like disease pattern 12, neuritis 8, myelitis 7, Thrombotic/vasculitis |
N/A | Category 1 (acute COVID-19): 4 patients had patchy T2 hyperintensity involving gray and white matter which was referred to ADEM. 2 patients with myelitis 2 patients with enhancement of CN VII & XII; CN V &VIII 4 patients with co-infections and 3 of them had vasculitic/thrombotic findings. Category 2 (acute/subacute COVID-19): 3 patients had patchy T2 hyperintensity referred to ADEM and 2 had myelitis. 3 patients had enhancement of CN and cauda equina 1 patient with superior sagittal sinus thrombosis Category 3 (MIS-C): 7 had CC Splenial lesion T2 hyperintensity. 4 of them with ADEM like lesions; 2 had CN enhancement and 1 had enhancement of cauda equina Category 4 (indeterminate): 4 patients had enhancement of CN and/or cauda equina. 1 patient with infarction 2 patients with ADEM-like lesions | n = 27; normal at discharge/improvement at follow-up n = 4; died n = 5; residual neurological deficits |
| Baccarella et al., 2021 [53] | Clinical Letter, United States of America | Pediatric neurology | n = 2 9-year-old male 6-year-old male |
MIS-C: increased intracranial pressure Case 2 was with abducens palsy |
N/A | Brain MRI and MR venography of case1: normal Brain MRI of case 2: Magnetic resonance imaging of the brain and orbits was notable for kinking and distention of both optic nerve sheaths with protrusion of the optic discs into the globes, consistent with increased ICP. |
Resolved |
aAnterior cerebral artery (ACA); Acute disseminated encephalomyelitis (ADEM); acute inflammatory demyelinating polyneuropathy (AIDP); acute motor axonal neuropathy (AMAN); Corpus Callosum (CC); Cranial nerve (CN); Central nervous system (CNS); Computed tomography (CT); Electroencephalography (EEG); Electromyography (EMG); Extracorporeal membrane oxygenation (ECMO); Guillain-Barré syndrome (GBS); Magnetic resonance imaging (MRI); Magnetic resonance angiography (MRA); Middle cerebral arteria (MCA); Multisystem inflammatory syndrome in children (MIS-C); Month/year (m/y); Not available (N/A); Number (n); Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Status Epilepticus (SE).