Clinical features of SARS-CoV-2-associated encephalitis and meningitis amid COVID-19 pandemic

Table 1 Demographic and clinical characteristics of acute neurologic illness among patients with confirmed encephalitis/meningitis with evidence of severe acute respiratory syndrome coronavirus 2 infection

No.	Ref.	Age/Sex	Area	Past medical history	Viral syndrome	Diagnosis of COVID-19	TVC (d)	Neurological symptoms	Neurological signs	TVN (d)	Subtype	Primary target	Treatment	Outcome
1	16	NA/male	China	N/A	Fever, shortness of breath, myalgia	(+) RT-PCR/PS	N/A	Consciousness confusion	(+) Meningeal irritation signs (including nuchal rigidity, Kernig sign and Brudzinski sign) and extensor plantar response	14	ME	N/A	Supportive therapy (mannitol infusion, oxygen therapy), arbidol	Good: Consciousness was completely clear, hospital discharged
2	9	24 yr/male	Japan	N/A	Headache, fatigue, fever	(-) RT-PCR/NPS	N/A	Consciousness disturbance, seizures	(+) Neck stiffness	9	ME	Right lateral ventricle, mesial temporal lobe, hippocampus	N/A	N/A
3	2	23 yr/male	Italy	Substance abuse	Psychomotor agitation, thought disorganization, persecutory delusions, auditory hallucinations, anxiety, insomnia	(+) RT-PCR/PS	N/A	Dysphagia, dyskinesias, autonomic instabilities	Non responsive to commands, non-verbal, despite being able to move all his extremities and reacting to noxious stimuli	8	E	N/A	High doses of DEX, IVIg	Good: Clinical conditions are ameliorating
4	17	35 yr/female	Turkey	N/A	Mild flu-like complaints	(+) RT-PCR/PS	N/A	Headache, nausea, dizziness, seizure	N/A	14	E	Left anterior temporal lobe	Left anterior temporal lobectomy	Good: No post-operative neurological deficits, symptoms improved completely
5	36	36 yr/male	United Arab Emirates	N/A	Fever, headache, myalgia, cough, diarrhea, vomiting	(+) RT-PCR/PS	5	Drowsiness, consciousness confusion	(+) Mild neck stiffness	5	ME	Supratentorial leptomeningeal, right frontal lobe	N/A	Poor: The patient’s neurological symptoms was not improved
6	19	75 yr/male	Japan	Alzheimer’s disease	Diarrhea	(+) RT-PCR/PS	6	Left hand kinetic tremor, walking instability, urinary incontinence	(+) Finger-to-nose test; (+) ataxic gait was observed	6	E	Corpus callosum	Sulbactam/ampicillin, favipiravir, corticosteroid pulse, ciclesonide, meropenem	Dead
7	20	31 yr/female	United States	Sickle cell disease	Progressive dyspnea	(+) RT-PCR/NPS	5	Paralysis	Coma	11	EM	Right cerebral hemisphere, cervical spinal cord	Hydroxychloroquine, peramivir	Dead
8	20	34 yr/male	United States	Hypertension	Fever, shortness of breath, cough	(+) RT-PCR/NPS	2	Consciousness disturbance, myoclonus	Absent corneal and gag reflexes, absent withdrawal to painful stimuli	9	E	Corpus callosum	Hydroxychloroquine	N/A
9	20	64 yr/male	United States	Hypertension	Cough, dyspnea, fever	(+) RT-PCR/NPS	N/A	Myoclonus	Absent oculocephalic reflex and withdrawal to pain, diminished deep tendon reflexes	N/A	E	Right temporal lobe	Hydroxychloroquine	Good: Hospital discharged without major neurologic sequelae
10	21	11 yr/male	United States	N/A	Generalized weakness, fever	(+) RT-PCR/PS	3	Status epilepticus	N/A	3	E	Frontal lobe	Anticonvulsant medications	Good: Recovery
11	22	39 yr/female	Iran	N/A	Fever, myalgia, dry cough	(+) Anti-SARS- CoV-2-IgM, IgG in serum	10	Drowsiness, decline unconsciousness, seizure, headaches	N/A	10	E	Temporal lobe, pontine, thalami	Broad-spectrum IV antibiotics, hydroxychloroquine, atazanavir, IVIg, levetiracetam, methylprednisolone	Good: Normal consciousness, no diplopia or other abnormal findings
12	37	42 yr/female	Brazil	N/A	Coryza, nasal obstruction	(-) RT-PCR/NPS	N/A	Paresthesias (left upper limb, left hemithorax, and hemiface)	Hypoesthesia in left upper limb, left hemithorax, and hemiface	21	EM	Cervical spinal cord	Corticosteroids	Good: Recovery
13	23	40 yr/male	United Kingdom	Hypertension, glaucoma	Fever, progressive dyspnea, cough, diarrhea	(+) RT-PCR/NPS	11	Unsteady gait, diplopia, oscillopsia, limb ataxia, altered sensation in right arm, hiccups and dribbling when eating or drinking	Facial weakness, reduced tongue movements, limb ataxia	13	RE, myelitis	Brain stem; cervical spine	Gabapentin	Good: Neurological symptoms improved steadily and hospital discharged
14	24	41 yr/female	United States	Diabetes	Headache, fever	(+) RT-PCR/PS	3	Headache, seizure	(+) Neck stiffness, photophobia	2	ME	N/A	Antibiotics, acyclovir, anti-epileptic medication, hydroxychloroquine	Good: The patient's mentation improved and was able to ambulate, eat and use the bathroom, but the hallucinations remained intermittently
15	25	69 yr/male	France	Diabetes, hypertension	Cough, fever, anosmia	(+) RT-PCR/tracheal aspirate	5	Status epilepticus	N/A	5	E	Right frontal lobe	IVIg	Good: Improved
16	26	49 yr/male	Turkey	N/A	Dyspnea	(+) RT-PCR/PS	N/A	Consciousness disturbance, delirium	N/A	N/A	E	White matter, cortical	Plasmapheresis treatment, LOP/RIT, AZI, CEF	Good: Consciousness was improved
17	26	59 yr/male	Turkey	Hypertension	Dyspnea	(+) RT-PCR/PS	N/A	Consciousness disturbance, delirium	N/A	N/A	E	White matter, cortical	Plasmapheresis treatment, AZI, HC, FAV	Good: Consciousness was improved
18	26	59 yr/male	Turkey	Hypertension, diabetes, obesity	Dyspnea	(+) RT-PCR/PS	N/A	Consciousness disturbance, delirium	N/A	N/A	M	N/A	Plasmapheresis treatment, AZI, HC, FAV	Dead: Cardiac arrest
19	26	51 yr/female	Turkey	Hypertension, diabetes	Dyspnea	(+) RT-PCR/PS	N/A	Consciousness disturbance, delirium	N/A	N/A	M	N/A	Plasmapheresis treatment, AZI, HC, FAV	Good: Consciousness was improved
20	26	55 yr/male	Turkey	Hypertension	Dyspnea	(+) RT-PCR/PS	N/A	Consciousness disturbance, delirium	N/A	N/A	M	N/A	Plasmapheresis treatment, AZI, HC, FAV	Poor: Subsequent infection
21	26	22 yr/male	Turkey	Autism	Dyspnea	(+) RT-PCR/PS	N/A	Consciousness disturbance, delirium	N/A	N/A	E	White matter	Plasmapheresis treatment, AZI, HC, FAV	Good: Consciousness was improved
22	33	40 yr/female	United States	Obesity, diabetes mellitus	Fever	(+) RT-PCR/NPS	N/A	Syncope	N/A	1	E	N/A	Hydroxychloroquine	Good: Recovery without neurological deficits
23	27	60 yr/male	United Kingdom	N/A	Fever, cough, cognitive fluctuations	(+) RT-PCR/NPS	5	Irritability, confusion, asthenia, consciousness	(+) Palmomental and glabella reflexes, mutism, (+) moderate nuchal rigidity, severe akinetic syndrome	1	E	N/A	Lopinavir/ritonavir, hydroxychloroquine, ampicillin, acyclovir	Good: Normal neurological examination and hospital discharged
24	28	64 yr/female	Switzerland	N/A	Weakness, cough, myalgia	(+) RT-PCR/NPS	N/A	Tonico-clonic seizure	Disoriented, attention deficit, bilateral grasping, psychotic symptoms (hyper-religiosity with mystic delusions, visual hallucinations), averbal and motor perseverations	6	E	N/A	Clonazepam, valproate, acyclovir	Good: Improved
25	28	67 yr/female	Switzerland	N/A	Cough	(+) RT-PCR/NPS	N/A	Headache, syncope	Motor perseverations, bilateral grasping, aggressiveness, left hemianopia and sensory hemineglect	18	E	N/A	Ceftriaxone, amoxicillin, acyclovir	Good: Neurological symptoms resolved, except for a mild headache, hospital discharged
26	29	8 yr/male	South Asian	N/A	Fever, abdominal pain, palmar rash, vomiting	(+) RT-PCR/NPS	N/A	Confused, agitated, headache	(+) Meningeal irritation signs (including nuchal rigidity, Kernig sign and Brudzinski sign), generalized proximal weakness	1	ME	Corpus callosum	IVIg, dexamethasone, anakinra	Poor: Still inpatient, wheelchair bound
27	29	9 yr/male	Caribbean	N/A	Fever, palmar rash, vomiting	(+) RT-PCR/NPS	N/A	Confused, ataxia, dysarthria, headache	Urinary retention, bilateral proximal leg weakness	1	E	Corpus callosum	N/A	Good: Hospital discharged
28	30	64 yr/male	China	Health	Fever, cough	(+) RT-PCR/PS	15	Lethargic, unresponsive	(+) Meningeal irritation signs (nuchal rigidity, Kernig sign, Brudzinski sign), consciousness alternating between lethargy and irritability, responses to questions were incorrect, (+) ankle clonus, Babinski sign and Chaddock sign	14	M	N/A	Oxygen inhalation, arbidol, ribavirin, traditional Chinese medicine	Good: Clear consciousness, limb reflexes were relatively active, left lower limb was positive for pathological signs
29	31	50 yr/female	United States	N/A	Cough, fever	(+) RT-PCR/PS	2	Altered mental status	N/A	2	E	Thalami, temporal lobe, insular lobe	IVIg	N/A
30	18	56 yr/male	China	N/A	N/A	(+) RT-PCR/PS	N/A	Consciousness confusion	N/A	N/A	M	N/A	N/A	Good: Neurological symptoms gradually disappeared
31	33	65 yr/female	United Kingdom	N/A	N/A	(+) RT-PCR/NPS	N/A	Reducedconsciousness	N/A	N/A	E	N/A	1 g IVMP 3 d, oral prednisolone taper, levetiracetam, clonazepam	Poor: Incomplete, partial recovery
32	33	66 yr/female	United Kingdom	N/A	N/A	(+) RT-PCR/NPS	N/A	Reducedconsciousness	N/A	N/A	E	Upper pons, limbic lobes, medial thalami, subcortical cerebral white matter	1 g IVMP 3 d then oral prednisolone taper, IVIg	Poor: Incomplete, partial recovery

NA: Not available; M: Male; F: Female; (+): Positive; TVC: Time between reported viral syndrome and confirmed coronavirus disease-19; TVN: Time between reported viral syndrome and onset of neurological symptoms (d); PS: Pharyngeal swab; NPS: Nasopharyngeal swab; E: Encephalitis; M: Meningitis; ME: Meningoencephalitis; EM: Encephalomyelitis; RE: Rhombencephalitis; WBCs: White blood cells; CRP: C-reactive protein; LDH: Lactate dehydrogenase; CSF: Cerebrospinal fluid; LOP: Lopinavir; RIT: Ritonavir; AZI: Azitromisin; HC: Hydroxychloroquine; CEF: Ceftriaxone; FAV: Faviripavir; IL-6: Interleukin-6; MRI: Magnetic resonance imaging; AlbQ: Albumin quotient; IVIg: Intravenous immune globulin.