Table 1 Reported cases of neurological involvement during SARS-CoV-2 infection in children
Author/Country [Ref.] | Age/sex | Pre-existing medical conditions | Neurological symptoms | Respiratory symptoms | Other symptoms | Diagnosis of MIS-C | NP/CSF/Serology SARS-CoV-2 | Radiology and other neurological investigations | Outcome |
|---|---|---|---|---|---|---|---|---|---|
Abdel-Mannan et al./UK [12] 4 cases | 8 y/M | No | Headache, meningism, confusion, muscular weakness | No | Fever, rash, abdominal pain, emesis, shock | Yes | Pos/Neg/ND | CT: hypodensity of the splenium of the corpus callosum | Improved |
9 y/M | No | Headache, confusion, ataxia, dysarthria, muscular weakness | No | Fever, rash, emesis, shock | Yes | Pos/Neg/ND | MRI: signal changes of the genu and splenium of corpus callosum and bilateral centrum semiovale with restricted diffusion | Recovered | |
15 y/F | No | Confusion, dysarthria, dysphagia, muscular weakness | Yes | Fever, rash, emesis, shock | Yes | Pos/ND/Pos | MRI: signal changes in the splenium of corpus callosum and bilateral centrum semiovale with restricted diffusion | Improved | |
15 y/F | No | Headache, confusion, muscular weakness | Yes | Fever, rash, emesis, shock | Yes | Pos/ND/Pos | MRI: signal change in the splenium of corpus callosum with restricted diffusion | Recovered | |
Abel et al./USA [13] | 3 y/M | No | Irritability, hypotonia, muscular weakness | Yes | Fever, rash, emesis | Yes | Neg/Neg/Pos | MRI: restricted diffusion in the bilateral lateral thalamic nuclei EEG: moderate slow background activity | Improved, under physiotherapy |
Asif et al./UK [14] | 18 y/M | No | Headache, photophobia | No | Fever, cough and myalgia before neurological manifestations | No | Neg/ND/ND (previous diagnosis of COVID-19) | CT venogram: filling defects in the sigmoid and transverse sinuses bilaterally and in the straight and superior sagittal sinuses | Improved |
Baccarella et al./US A[15]2 cases | 9 y/M | No | Headache, diplopia, right abducens nerve palsy | No | Fever, abdominal pain | Yes | Neg/Neg/Pos | MRI: normal LP: elevated opening pressure | Recovered |
6 y/M | No | Headache, diplopia, right abducens nerve palsy | No | NR | Yes | Pos/Neg/Pos | MRI: finding consistent with elevated intracranial pressure | Recovered | |
Basirjafari et al./Iran [16] | 9 y/M | No | Headache, bilateral fixed mydriasis | Yes | Fever, abdominal pain | No | Pos/ND/ND | CT: hyperdensity at basal cisterns, interhemispheric and bilateralSylvian fissures suggesting of subarachnoid hemorrhage and reduction of white matter density (brain edema) | Died |
Bektas et al./Turke y[17]2 cases | 10 y/M | No | Visual hallucinations, personality changes | Yes | Fever, diarrhea, rash, hands and feet edema | Yes | Neg/ND/Pos | MRI: hyperintensity in the splenium of corpus callosum with restricted diffusion EEG: slowed background activity | Recovered |
11 y/F | No | Personality changes | Yes | Fever, diarrhea, rash, conjunctivitis, hypotension | Yes | Neg/ND/Pos | MRI: hyperintensity in the splenium of corpus callosum with restricted diffusion EEG: slowed background activity | Recovered | |
Bhatta et al./USA [18] | 11 y/M | No | Seizure | No | No | No | Pos/NR/ND | CT: normal | Recovered |
Burr et al./USA [19] | 23 m/F | No | Irritability, hyperkinetic movements of head, arms and legs | No | Fever | No | Pos/Neg/Pos | MRI: normal NMDAR-IgG positivity | Recovered |
Chiotos et al./US A[20]4 cases | 14 y/F | No | Headache | Yes | Fever, rash, diarrhea | Yes | Neg/ND/Pos | ND | Recovered |
12 y/M | No | Altered mental status, irritability | Yes | Fever, fissured lips, abdominal pain, diarrhea, shock | Yes | Neg/ND/Pos | ND | Recovered | |
5 y/F | No | Altered mental status, irritability, nuchal rigidity | No | Fever, conjunctivitis, shock | Yes | Neg/ND/Pos | ND | Recovered | |
5 y/F | No | Irritability, nuchal rigidity | No | Fever, rash, conjunctivitis, fissured lips, swollen hands, emesis, diarrhea, shock | Yes | Pos/ND/Pos | CT: diffuse cerebral edema | Recovered | |
Curtis et al./India [21] | 8 y/M | No | Muscolar weakness, paralysis and paresthesia of the lower limbs | No | No | No | Pos/Neg/Pos | MRI: enhancement of the posterior nerve roots from T11 to cauda equine LP: albuminocytologic dissociation | Improved |
de Miranda Henriques-Souza et al./Brazil [22] | 12 y/F | No | Headache, muscular weakness, tetraplegia | Yes | Fever, rash | Yes | Pos/Neg/ND | MRI: bilateral and symmetric areas of restricted diffusion involving the subcortical and deep white matter. Extensive cervical myelopathy | Improved |
De Paulis et al./Brazil [23] | 4 y/F | No | Confusion, lethargy | Yes | Fever, emesis, rash, palpebrae, hands and feet edema, cracked lips, shock | Yes | Neg/Neg/Pos | CT: normal LP: pleiocytosis and elevated protein | Improved |
Emami et al./Iran [24] | 2.9 y/M | Allergy to cow milk | Seizure, altered mental status, dysarthria | No | Fever | No | Pos/ND/NR | MRI: right occipital mass andintracerebral hemorrhage EEG: generalized slowing (pathology of the mass: normal brain tissue with dilated vessels and haemorrhage) | Recovered |
Enner et al./USA [25] | 14 y/F | No | Seizure and central apnea | Yes | Fever, nasal congestion, myalgia | No | Pos/Neg/ND | MRI: normal EEG: epileptiform abnormalities | Improved |
Frank et al./Brazil [26] | 15 y/M | No | Ascending weakness froma the lower to the upper limbs, headache | No | Fever | No | Pos/Neg/Pos | MRI: normal Electroneurography: acute motor axonal neuropathy | Improved, under physiotherapy |
Gaur et al./ U K[27]2 cases | 12 y/M | NR | Headache, lethargy | No | Fever, diarrhea, conjunctivitis, shock | Yes | Neg/ND/Pos | MRI: hyperintensity in the splenium of corpus callosum with restricted diffusion | Recovered |
9 y/M | NR | Lethargy, ataxia, dysarthria | No | Fever | No | Neg/ND/NDPos broncho-alveolar lavage | MRI: hyperintensity in the splenium of corpus callosum and in the deep cerebral white matter with restricted diffusion | Recovered | |
Gulko et al./USA [28] | 13 y/F | No | Headache, muscular weakness, speech difficulty | No | No | No | Pos/ND/ND | CT: left frontal hypodensity concerning for ischemic infarct. MRI: hyperintensity with restricted diffusion in the left frontal, parietal and temporal lobes; stenosis of the left middle cerebral artery | Improved |
Kaur et al./Mexico [29] | 3 y/F | No | Quadriparesis and paresthesia | Yes | Neurogenic respiratory failure | No | Pos/Neg/ND | MRI: swelling of the cervical spinal cord involving most of the transverse aspect of the spinal cord, extending from the lower medulla to the midthoracic level | Quadriparesis |
Khalifa et al./Saudi Arabia [30] | 11 y/M | No | Muscular weakness, hypotonia, paresthesia in the lower limbs | Yes | Fever and cough before neurological manifestations | No | Pos/NR/ND | MRI: cauda equina nerve root enhancement LP: albuminocytologic dissociation | Recovered |
Kim et al./USA [31] | 7 y/M | No | Headache, emesis | No | Fever, abdominal pain | Yes | Pos/Neg/ND | CT: diffuse cerebral edema EEG: generalized voltage attenuation | Died |
Lin et al./USA [32] | 13 y/F | No | Dizziness, gait instability, auditory hallucinations | Yes | Fever, diarrhea, emesis, hypotension | Yes | Pos/Neg/Pos | MRI: hyperintensity in the splenium of corpus callosum with restricted diffusion EEG: slow background activity | Recovered |
Lorenz et al./Germany [33] | 40 w/F | No | Lethargy, hyperexcitable | Yes | Fever | No | Pos/Neg/ND | US: normal | Recovered |
Manji et al./Tanzania [34] | 12 y/M | No | Progressive paresis, bilateral facial nerve paresis | Yes | Fever and cough before neurological manifestations | No | Pos/ND/ND | ND | Died |
McAbee et al./ USA [35] | 11 y/M | No | Seizure | No | Fever | No | Pos/Neg/ND | CT: normal EEG: intermittent frontal delta activity LP: pleiocytosis | Recovered |
Mirzaee et al./Iran [36] | 12 y/M | No | Seizure, dysarthria, hemiparesis | No | No | No | Pos/Pos/ND | MRI: acute infarction with narrowing of the left middle cerebral artery | Improved, under rehabilitation |
Moreno-Galarraga et al./Spain [37] | 2 m/F | No | Headache, seizure | No | Diarrhea Flu-like symptoms before neurological manifestations | No | Pos/NR/ND | MRI: normal LP: normal | Recovered |
Natarajan et al./India [38] | 13 y/F | No | Headache, irritability, seizure | No | Fever | No | Pos/Neg/ND | MRI: normal LP: pleiocytosis | Recovered |
Paybast et al./Iran [39] | 14 y/F | NR | Progressive paresthesia, muscular weakness, headache, dizziness | No | Flu-like symptoms before neurological manifestations | No | Pos/ND/ND | LP: albuminocytologic dissociation | Improved |
Raj et al./India [40] | 2 y/M | No | Seizure | No | Fever, diarrhea, hypotension | Yes | Pos/Neg/Neg | ND | Recovered |
15 m/M | No | Seizure | No | Fever, rash, conjunctivitis, cheilitis | Yes | NR/ND/NR(COVID-19 contact) | ND | Recovered | |
8 m/M | NR | Seizure | No | Fever | No | Pos/ND/ND | ND | Recovered | |
Regev et al./Israel [41] | 16 y/M | No | Headache, nuchal rigidity | No | Fever, abdominal pain, rash, conjunctivitis, pharyngitis, shock | Yes | Pos/ND/Pos | MRI: multiple low attenuating small lesionsin the subcortical white matter, internal and external capsule and in the anterior and posterior part of the corpus callosum, suggesting microhemorrhages | Recovered |
Roussel et al./France [42] | 6 y/F | Sickle cell disease, cerebral vasculopathy, HSCT | Impairment of V-VII-IX cranial nerves | Yes | No | No | Pos/Neg/ND | MRI: cranial nerves enhancement (left hypoglossal nerve and bilateral facial nerves) | Improved |
Saeed et al./Iran [43] | 3 y/M | No | Seizure | No | Fever, hypotension | Yes | Pos/Neg/ND | CT: cerebral edema MRI: intracerebral hemorrhage in the right occipital lobe | Recovered |
Savić et al./Kuwait [44] | 13 y/F | No | Altered mental status, right side weakness | No | No | No | Pos/ND/ND | CT: left side frontoparietal intracerebral hematoma with intraventricular extension CT angiography: pseudoaneurysm of the frontoparietal branch of the left middle cerebral artery | Not improved |
Schupper et al./USA [45] | 5 y/M | No | Right mydriasis | Yes | Fever, abdominal pain, shock | Yes | NR/NR/Pos | CT: a right middle cerebral artery infarction, cerebral edema and diffuse contralateral subarachnoid hemorrhage | Died |
Seth et al./India [46] | 15 y/M | NR | Headache, emesis, photophobia | No | Fever before neurological manifestations | No | Pos/Neg/ND | MRI: normal LP: elevated opening pressure and pleiocytosis | Recovered |
Shenker et al./USA [47] | 12 y/M | NR | Seizure | No | Fever, rash, conjunctivitis, neck swelling, cracked lips, hypotension | Yes | Pos/Neg/ND | MRI: normal EEG: focal epilepsy arising in the central region | Recovered |
Swarz et al./USA [48] | 9 y/M | No | Seizure | No | Fever, emesis | No | Pos/ND/ND | MRI: normal EEG: delta activity in the right hemisphere | Recovered |
Theophanous et al./USA [49] | 6 y/M | Prematurity, chromosome 17 and 19 deletions, submucosal palate cleft, atrial and ventricular septal defects, agammaglobulinemia with hyper-IgM, hypospadias, asthma, OSAS, gastrostomy | Right facial nerve palsy | No | No | No | Pos/ND/ND | ND | Recovered |
Tiwari et al./India [50] | 9 y/F | No | Headache, right hemiplegia, right facial nerve palsy | Yes | Fever, conjunctivitis, emesis | Yes | Pos/Neg/Pos | CT: multifocal hypodensities in the genu and body of corpus callosum, left basal ganglia and bilateral thalami suggestive of infarcts CT angiography: multifocal stenosis of both intracranial internal carotid arteries, right middle cerebral artery, both A2 segments of the anterior cerebral arteries and M2/M3segments of both middle cerebral arteries | Improved, under rehabilitation |
Verdoni et al./Ital y[5]5 cases | 7 y/M | No | Meningism | Yes | Fever, conjunctivitis, changes in lips and oral cavity, diarrhea | Yes | Pos/ND/Pos | ND | Recovered |
7.7 y/F | Congenital adrenal hyperplasia | Meningism | No | Fever, conjunctivitis, changes in lips and oral cavity, diarrhea | Yes | Neg/ND/Pos | ND | Recovered | |
5 y/M | No | Meningism | No | Fever, rash, conjunctivitis hands and feet anomalies | Yes | Neg/ND/Pos | ND | Recovered | |
5.5 y/M | No | Meningism | No | Fever, rash, conjunctivitis hands and feet anomalies | Yes | Neg/ND/Pos | ND | Recovered | |
5.5 y/M | No | Drowsiness | Yes | Fever, rash, conjunctivitis hands and feet anomalies, diarrhea | Yes | Neg/ND/Pos | ND | Recovered | |
Verkuil et al./USA [51] | 14 y/F | No | Headache, right abducens nerve palsy | Yes | Fever, diarrhea, rash, shock | Yes | Neg/ND/Pos | MRI: finding consistent with elevated intracranial pressure LP: elevated opening pressure | Recovered |
Vivanti et al./Francea [52] | 3 d/M | Prematurity | Irritability, opisthotonos | No | Feeding difficulty | No | Pos/Neg/ND | MRI: hyperintensity of the periventricular and subcortical frontal and parietal white matter | Improved |
Yousefi et al./Iran [53] | 9 y/F | NR | Headache, diplopia, photophobia, meningism | No | Fever | No | Neg/Pos/ND | LP: pleiocytosis, elevated protein, decreased glucose | Recovered |
Zombori et al./UK [54] | 17 y/F | Cornelia de Lange syndrome | Seizure | Yes | Fever | Yes | Pos/ND/ND | MRI: multifocal cortical, cerebellar and thalamic swelling areas EEG: bilateral independent periodic lateralized epileptiform discharges | Improved, under rehabilitation |
Our case | 5 y/F | No | Irritability, nuchal rigidity | No | Fever, rash, diarrhea, neck swelling | Yes | Pos/ND/Pos | MRI: two lesions, one in the splenium of the corpus callosum and the other in the subcortical white matter of the left parietal lobe, with restricted diffusion | Recovered |