Table 1.

Summary of case reports (n = 19) which met all criteria for this meta-analysis.

Patient 1	Sanchez-Larsen et al. [67]	Female (22 years old). Known non-lesional focal right frontal lobe epilepsy since 2 years
	Reason for hospitalisation	4 focal to bilateral tonic-clonic seizures
	Respiratory (other) symptoms	COVID-19 positive (test method not mentioned) with mild flu-like symptoms Examination revealed no teratoma
	Neuropsychiatric symptoms	Severe anxiety, dysphoric mood, insomnia, motor aphasia, visual hallucination, three focal to bilateral tonic-clonic seizures within several hours, bradyphrenia, psychomotoric agitation
	Blood test	Normal
	CSF examination	White cell count 7/µl, normal protein and glucose levels. SARS-CoV-2 not mentioned. Additional virological and microbiological diagnostics negative. NMDAR-antibodies positive (Ig class and test method not mentioned).
	EEG	Frontal intermittent rhythmic delta activity, with no other relevant findings
	Brain imaging	MRI: normal (unclear if contrast agent was used)
	Therapy	Antiseizure therapy, benzodiazepines and antipsychotics administered After NMDAR encephalitis diagnosis, methylprednisolone, intravenous immunoglobulin and rituximab administered
	Course	Not mentioned
Patient 2	Valadez-Calderon et al. [79]	Male (28 years old)
	Reason for hospitalisation	Fronto-orbital syndrome characterized by catatonic symptoms
	Respiratory (other) symptoms	Mild COVID-19 (test method not mentioned)
	Neuropsychiatric symptoms	Incoherent speech, somnolence, auditory hallucinations, suicidal ideations and generalized tonic-clonic seizures, status epilepticus
	Blood test	Normal
	CSF examination	Initial CSF analysis was normal (white cell count not mentioned). SARS-CoV-2 PCR and anti-SARS-CoV-2 IgG negative. Additional virological and microbiological diagnostics negative. NMDAR- and GAD-65- antibodies positive (immunoblotting revealed IgG against NMDA receptor and GAD65/67 -> cell-based indirect immunofluorescence assay revealed cell-surface and intracellular antibody binding).
	EEG	Subcortical dysfunction in frontal, temporal and occipital regions
	Brain imaging	MRI: T2 FLAIR and diffusion-weighted imaging: bilateral hyperintensities in the anterior cingulated cortex and temporal lobes
	Therapy	Anti-seizure treatment After NMDAR encephalitis diagnosis, methylprednisolone and intravenous immunoglobulin
	Course	Physical rehabilitation, presents neurological sequelae related to mood disorders, irritability and agitation
Patient 3	Khoreva et al. [70]	Female (16 years old)
	Reason for hospitalisation	Fever
	Respiratory (other) symptoms	COVID-19 positive (SARS-CoV-2 PCR positive), mild symptoms, fever, headache, nausea, tachycardia and tachypnoea. Ovarian teratoma
	Neuropsychiatric symptoms	Personality changes, aggression, visual hallucinations, agitation, memory impairment, catatonia, epileptic seizure, coma
	Blood test	Not mentioned
	CSF examination	Lymphocytic pleocytosis (62 cells/µl), normal white cell count in second lumbar puncture, normal protein. No SARS-CoV-2 PCR testing performed. Additional virological and microbiological diagnostics negative, IgG-NMDAR-antibodies positive (cell-based indirect immunofluorescence assay)
	EEG	Not explicitely mentioned, likely abnormal due to multiple seizures.
	Brain imaging	MRI: normal (contract agent was used); FDG-PET: hyper-metabolism in the basal nuclei and cerebellum, diffuse cortical hypometabolism.
	Therapy	Antiviral, antibacterial, antipsychotic and antiseizure therapy Methylprednisolone and intravenous immunoglobulin Removal of teratoma
	Course	Antiseizure therapy and rehabilitation
Patient 4	Bazalar et al. [71]	Female (19 years old)
	Reason for hospitalisation	Psychiatric symptoms
	Respiratory (other) symptoms	COVID-19 positive (SARS-CoV-2 PCR positive), mild flu symptoms. Examination for ovarian teratoma not mentioned.
	Neuropsychiatric symptoms	Personality changes, aggression, audio-visual hallucinations, agitation, catatonia, epileptic seizure, coma
	Blood test	Leucocytosis and elevated CRP
	CSF examination	White celll count 95/µl, 70% lymphocytes. SARS-CoV-2 not mentioned. Additional virological and microbiological diagnostics negative. IgG-NMDAR-antibodies positive (cell-based indirect immunofluorescence assay).
	EEG	Diffuse, slow activity, intermittent delta waves
	Brain imaging	MRI: normal (no contrast agent was used)
	Therapy	Antipsychotic treatment Antiviral prophylactic and antiseizure therapy Methylprednisolone, intravenous immunoglobulin and rituximab
	Course	marked improvement, after sixth dose of rituximab, discharged
Patient 5	Gillentine et al. [73]	Female (37 years-old)
	Reason for hospitalization	Headache, general malaise, fever and upper respiratory tract symptoms COVID-19-positive (test method not mentioned) 6 weeks earlier with uncomplicated course
	Respiratory (other) symptoms	Severe respiratory distress, subsequently intubated Benign ovarian teratoma of left ovary
	Neuropsychiatric symptoms	Visual hallucinations and paranoid behaviour, increased agitation, catatonia
	Blood test	Leucocytosis
	CSF examination	Lymphocytic pleocytosis (white cell count not shown) and elevated protein. SARS-COV-2 antibodies negative. Additional virological and microbiological diagnostics negative. IgG NMDAR-antibodies positive (cell-based indirect immunofluorescence assay).
	EEG	Epileptic focus in the right parietal region
	Brain imaging	MRI: normal (unclear if contrast agent was used)
	Therapy	Antiviral and antibacterial treatment Later steroids, intravenous immunoglobulins and rituximab Prophylactic bilateral salpingo-oophorectomy
	Course	After 56 hospital days the patient died
Patient 6	Kaur et al. [80]	Male (10 months old)
	Reason for hospitalization	Poor feeding and irritability for 5 days, 2 episodes of convulsion
	Respiratory (other) symptoms	Moderate symptoms: 40 days before admission upper respiratory tract infection, SARS-COV-2 IgG strongly positive
	Neuropsychiatric symptoms	Poor interactions with caregivers Extrapyramidal movements with generalized and oro –linguo-buccal dystonia with athetosis
	Blood test	Leucocytosis, SARS-COV-2 IgG strongly positive
	CSF examination	White cell count 20/µl, 95% lymphocytes. SARS-CoV-2 not mentioned. Additional virological and microbiological diagnostics negative. NMDAR-antibodies positive (Ig class unclear, cell-based indirect immunofluorescence assay).
	EEG	Not mentioned
	Brain imaging	MRI: normal (unclear if contrast agent was used)
	Therapy	Methylprednisolone, intravenous immunoglobulin and rituximab Azathioprine, cyclophosphamide and extrapyramidal movements treatment
	Course	Extrapyramidal movements well controlled and baby regained age-appropriate milestones
Patient 7	Alvi et al. [74]	Female (13 years old)
	Reason for hospitalization	Behavioural issues for one week with intermittent aggression and irritability with disturbed sleep/wake cycle No CoViD-19 vaccination
	Respiratory (other) symptoms	No respiratory or gastrointestinal symptoms, tachycardiac MRI of pelvis and abdomen were unremarkable
	Neuropsychiatric symptoms	Three episodes of generalized tonic clonic seizures with worsened conscious level
	Blood test	SARS-COV-2 antibodies (type of antibodies not mentioned) positive
	CSF examination	Normal protein and cell quantity. SARS-CoV-2 not mentioned. Additional virological and microbiological diagnostics negative. NMDAR-antibodies positive (Ig class and test method not mentioned).
	EEG	Delta brush pattern
	Brain imaging	MRI: normal (unclear if contrast agent was used)
	Therapy	Anti-seizure treatment Methylprednisolone, plasmapheresis and rituximab
	Course	Residual deficit in executive function still present
Patient 8	Naidu and Tayler [75]	Female (50 years old)
	Reason for hospitalization	Fever, cough, myalgia
	Respiratory (other) symptoms	COVID-19 positive (test method not mentioned). No respiratory symptoms. Severe nausea and vomiting Ovarian tumors were excluded
	Neuropsychiatric symptoms	Progressive weakness of all limbs, confusion and disorganised behaviour Later emotional lability, quadriparesis, left sided sensory deficits, slurred speech, urinary retention and cognitive impairment
	Blood test	Elevated CRP, increased D-dimer
	CSF examination	White cell count 0/µL (no pleocytosis), elevated protein and IgG. SARS-CoV-2 not mentioned. Additional virological and microbiological diagnostics negative. IgG NMDAR-antibodies positive (cell-based indirect immunofluorescence assay).
	EEG	Abnormal EEG: bilateral fronto-central delta to theta slowing noted intermittently. No delta brushes seen. Intermittent right sided P4 epileptiform sharp wave activity with field spread.
	Brain imaging	MRI with gadolinium: bilateral hyper-intense T2 and FLAIR lesions in the corticospinal tracts
	Therapy	Valproate, corticosteroids, intravenous immunoglobulin and plasmapheresis Rituximab as long term therapy
	Course	Significant improvement of symptoms.
Patient 9	Khubetova [81]	Male (45 years old). Chronic kidney failure Dialysis
	Reason for hospitalization	Severe lethargy, speech and swallowing disorders
	Respiratory (other) symptoms	No respiratory symptoms. COVID-19 positive (test method not mentioned), creatinine increase
	Neuropsychiatric symptoms	Bradyphrenia, bradylalia, bradykinesia, hyposmia, bilateral achyrokinesis
	Blood test	Elevated CRP and IL-6. NMDAR-antibodies positive (Ig class and test method not mentioned).
	CSF examination	Unclear if NMDAR-antibodies were tested in CSF or only in blood (see above).
	EEG	Not mentioned
	Brain imaging	MRI: multiple foci of gliosis in both hemispheres, probably of vascular origin (unclear if contrast agent was used)
	Therapy	Amantadine, citicoline
	Course	Improvement of neurological symptoms
Patient 10	Lee et al. [68]	Female (20 years old)
	Reason for hospitalisation	Convulsive seizure
	Respiratory (other) symptoms	No symptoms, COVID-19 negative 3 days before admission: vaccination with BNT162b2, expression of SARS-CoV-2 spike protein in cells by vaccination with mRNA (Pfizer-BioNTech) Bilateral ovarian teratoma
	Neuropsychiatric symptoms	Repetitively asking the same questions, Sent inappropriate text messages to friends Disturbances of comprehension and reading, seizure.
	Blood test	NMDAR-antibodies positive (test method or type of antibodies not mentioned)
	CSF examination	White cell count 58/µl, mainly lymphocytic, mild elevation of protein, Virological diagnostics negative. IgG NMDAR-antibodies positive (cell-based indirect immunofluorescence assay).
	EEG	Frequent spike-and-waves in bilateral temporal areas
	Brain imaging	MRI: normal except leptomeningeal enhancement and gyral swelling in both cerebral convexity on T1-weighted contrast-enhanced images and subtle signal change on T2-weighted and FLAIR images
	Therapy	Antiviral prophylactic therapy After NMDAR encephalitis diagnosis, methylprednisolone, intravenous immunoglobulin and rituximab Removal of teratoma
	Course	Fully recovered
Patient 11	Flannery et al. [69]	Female (in her 20’s)
	Reason for hospitalisation	Urinary frequency (subjective reason) and anxiety
	Respiratory (other) symptoms	No symptoms, COVID-19 negative 1 week before admission: vaccination with BNT162b2, expression of SARS-CoV-2 spike protein in cells by vaccination with mRNA (Pfizer-BioNTech) Chest x-ray and CT, and MRI of the chest, pelvis (exclusion of ovarian teratoma), and abdomen were unremarkable During admission, tachycardia and hypertension
	Neuropsychiatric symptoms	Anxiety, decreased mentally acuity, insomnia and fixation that she suffered from irritable bowel and kidney disease Motor dysfunction and transient aphasia Later auditory hallucinations, psychotic symptoms and catatonia
	Blood test	Mild leucocytosis, increased alanine aminotransferase and aspartate aminotransferase. NMDAR-antibodies positive (commercial IgG assay)
	CSF examination	White cell count 7/µL, 89% lymphocytes. Virological diagnostics negative. IgG NMDAR-antibodies positive (cell-based indirect immunofluorescence assay).
	EEG	No abnormalities
	Brain imaging	MRI: normal (unclear if contrast agent was used)
	Therapy	Antipsychotic treatment Methylprednisolone, intravenous immunoglobulin and rituximab Metoprolol to manage tachycardia and hypertension
	Course	Absence of seizures, improvement of neurological symptoms
Patient 12	Hina Naz et al. [72]	Female (33 years old)
	Reason for hospitalisation	Psychiatric symptoms
	Respiratory (other) symptoms	COVID-19 negative 1 day before admission: vaccination with BBIBP-CorV, whole inactivated virus (Sinopharm). Mild flu-like symptoms. Pelvis MRI was unremarkable
	Neuropsychiatric symptoms	Personality changes, memory impairment, aggression, audio-visual hallucinations, agitation, catatonia, epileptic seizure, coma
	Blood test	Polyclonal IgG bands
	CSF examination	White cell count 363/µl, 94% lymphocytes, elevated protein. Oligoclonal IgG bands positive in CSF. Virological and microbiological diagnostics negative. NMDAR-antibodies positive (Ig class and test method not mentioned).
	EEG	Diffuse, slow activity, bilateral spikes and slow waves discharges in frontocentral regions
	Brain imaging	MRI: normal (contract agent was used)
	Therapy	Antiviral prophylactic and antiseizure therapy Methylprednisolone, intravenous immunoglobulin and rituximab
	Course	Fully recovered
Patient 13 (Patient 1 in [45])	Panariello et al. [82]	Male (23 years-old). History of drug abuse
	Reason for hospitalisation	Psychomotor agitation, anxiety, formal thought disorder, persecutory delusions and auditory hallucinations and global insomnia. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing
	Respiratory (other) symptoms	Moderate fever, drop in O2 saturation, chest X-ray: bilateral milk glass opacities, chest CT: patchy bibasilar consolidation
	Neuropsychiatric symptoms	Confusion, disorganization of speech, thought/behaviour, auditory hallucinations and insomnia. Week 2: mutistic/non-responsive. Week-3: dysphagia, dyskinesia, autonomic instability, fluctuations in body temperature, blood pressure, pulse and respiratory rate
	Blood test	CRP elevated, leukocytosis, hyponatremia at time of NMDAR encephalitis diagnosis
	CSF examination	Red and white cell count elevated (960/µL, artificial?), elevated protein. SARS-CoV-2 negative (PCR test). Additional virological and microbiological diagnostics negative. IL-6 elevated, IgG-NMDAR-antibodies positive (cell-based indirect immunofluorescence assay).
	EEG	Theta activity, unstable, non-reactive to visual stimuli
	Brain imaging	CT scan was negative for neuroanatomical acute abnormalities.
	Therapy	Seizure prophylaxis. No symptom improvement with antipsychotics. COVID-19 therapy with hydroxychloroquine and darunavir/cobicistat. Antibiotic prophylactic therapy. After NMDAR encephalitis diagnosis, dexamethasone and intravenous immunoglobulin
	Course	Clinical symptoms improved
Patient 14 (Patient 2 in [45])	Alvarez Bravo and Ramio [76]	Female (30 years-old). No previous medical history. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing
	Reason for hospitalisation	Behavioral changes
	Respiratory (other) symptoms	Severe fever, pneumonia, thrombosis of the left iliac vein, and bilateral pulmonary embolism attributed to SARS-CoV-2 infection. Ovarian teratoma
	Neuropsychiatric symptoms	Psychomotor agitation, paranoid ideation, dysarthria with dysprosody, and visual hallucinations, focal and generalised seizures
	Blood test	Routine blood test: normal.
	CSF examination	White cell count 44/µL, 90% lymphocytes, protein elevated. SARS-CoV-2 negative (PCR test), Additional virological and microbiological diagnostics negative. IgG NMDAR antibodies positive (cell-based indirect immunofluorescence assay).
	EEG	Delta brush pattern, epileptic discharges in the left frontotemporal region
	Brain imaging	Hyperintensities in the left hippocampus in T2-weighted FLAIR sequences
	Therapy	After NMDAR encephalitis diagnosis, 5 days of methylprednisolone and immunoglobulins administered. Ovarian teratoma was removed by laparotomy.
	Course	Hypoprosexia, emotional lability and memory disorder, Stabilised systemic and respiratory symptoms
Patient 15 (Patient 3 in [45])	Allahyari et al. [77]	Female (18 years-old). No previous medical history. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing
	Reason for hospitalisation	Generalized tonic-clonic seizures
	Respiratory (other) symptoms	Moderate fever, pneumonia, hypotonia, tachycardia, tachypnea, oxygen saturation of 90%, bilateral pulmonary crackles in lower lung zones, Examination for ovarian teratoma not mentioned.
	Neuropsychiatric symptoms	3-week history of mood change as depression and anhedonia accompanied by lack of concentration, generalized tonic–clonic seizures
	Blood test	Neutrophilia, lymphopenia, CRP elevated
	CSF examination	White cell count 27/µL, 93% lymphocytes. SARS-CoV-2 positive (PCR test). Additional virological and microbiological diagnostics negative. IgG NMDAR antibodies positive (cell-based indirect immunofluorescence assay).
	EEG	Epileptic discharges in the left frontotemporal region
	Brain imaging	MRI: normal
	Therapy	Seizure prophylaxis. COVID-19 therapy with Remdesivir, Lopinavir/Ritonavir, and Interferon b1a (Resi- gen). Antibiotic prophylactic therapy. After NMDAR encephalitis diagnosis, methylprednisolone and intravenous immunoglobulin
	Course	After 2 months of hospitalization discharged with full recovery
Patient 16 (Patient 5 in [45])	Monti et al. [83]	Male (50 years-old). Moderate arterial hypertension
	Reason for hospitalisation	Acute psychiatric symptoms. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing
	Respiratory (other) symptoms	No respiratory symptoms. No diarrhoea. Fever present
	Neuropsychiatric symptoms	Confabulations and delirium. Day-4: focal motor seizures with reduced consciousness, orofacial dyskinesia, automatisms. Sudden refractory status epilepticus
	Blood test	IL-6 elevated. No CRP elevation or leukocytosis
	CSF examination	Three lumbar punctures: White cell count 76/µL and 25/µL, oligoclonal bands. SARS-CoV-2 not mentioned. Additional virological and microbiological diagnostics negative. Third lumbar puncture: IgG NMDAR antibodies positive (cell-based indirect immunofluorescence assay), IL-6 elevated.
	EEG	Diffuse delta activity with extreme delta brush pattern. Anterior subcontinuous periodic theta activity
	Brain imaging	MRI: normal
	Therapy	Antiepileptics and anaesthetics. COVID-19 therapy with hydroxychloroquine and lopinavir/ritonavir. After diagnosis of NMDAR encephalitis: corticosteroids, immunoglobulins and plasmapheresis
	Course	4 months after symptom onset patient discharged in good condition with no neuropsychiatric symptoms
Patient 17 (Patient 6 in [45])	Burr et al. [78]	Female (23 months-old). Vaccinated. No previous diseases. Family history unremarkable
	Reason for hospitalisation	Fever, psychomotor agitation, was no longer talking, sleep disturbances, constipation, decreased oral intake. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing
	Respiratory (other) symptoms	No respiratory symptoms. Fever, dehydration present. Examination for ovarian teratoma not mentioned.
	Neuropsychiatric symptoms	Agitation, poor sleep, mood swings, mutism, regular kicking/ fapping of extremities. Day-2: multiple epileptic seizures. Week 2: worsening encephalopathy with persistent hyperkinetic movements of extremities and head
	Blood test	CRP normal, NMDAR antibodies (IgG) positive (test method not mentioned).
	CSF examination	White cell count 7/µL, 89% lymphocytes, oligoclonal bands not tested. SARS-CoV-2 negative (PCR test). Additional virological and microbiological diagnostics negative. IgG NMDAR antibodies positive (cell-based indirect immunofluorescence assay).
	EEG	Not mentioned
	Brain imaging	MRI with and without contrast: normal
	Therapy	Antiepileptics. After NMDAR encephalitis diagnosis, corticosteroid therapy for 5 days with no improvement, followed by intravenous immunoglobulin administration
	Course	Remission within one week after immunoglobulin therapy
Patient 18 (Patient 7 in [45])	Sanchez-Morales et al. [84]	Male (14 years-old). No previous medical history. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing
	Reason for hospitalisation	Behavioural changes and neurological symptoms
	Respiratory (other) symptoms	None
	Neuropsychiatric symptoms	Altered behaviour and mental status, epileptic seizures, insomnia, orolingual dyskinesia
	Blood test	SARS-CoV-2 IgM and IgG negative
	CSF examination	White cell count 2/µL (no pleocytosis). SARS-CoV-2 positive (PCR test and IgG). Additional virological and microbiological diagnostics negative. NMDAR antibodies positive (Ig class and test method not mentioned).
	EEG	Not mentioned
	Brain imaging	MRI was done, findings were not mentioned
	Therapy	After NMDAR encephalitis diagnosis, methylprednisolone and immunoglobulins administered
	Course	Complete remission of neurological impairment. Control of epilepsy. Persistence of psychiatric symptoms
Patient 19 (Patient 8 in [45])	Sarigecili et al. [85]	Male (7 years-old). Vaccinated. No previous diseases. No abnormal family history
	Reason for hospitalisation	Gait disorder. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing
	Respiratory (other) symptoms	None. No headache, fever, or cold symptoms. Day 8: tachycardia
	Neuropsychiatric symptoms	Ataxia and broad-based gait with poor muscle reflexes. Day-2: somnolence and epileptic seizures. Day 8: choreiform movements of extremities, tongue protrusion, bruxism, smacking, psychomotor agitation, catatonia, echolalia
	Blood test	CRP elevated, lymphopenia. IL-6 not mentioned
	CSF examination	No cells present, oligoclonal bands negative. SARS-CoV-2 not mentioned. Additional virological and microbiological diagnostics negative. IgG NMDAR antibodies positive (test method not mentioned). IL-6 not mentioned
	EEG	Encephalopathic pattern with disseminated delta waves
	Brain imaging	MRI: normal
	Therapy	Antiepileptics after onset of seizures. Initial therapy with antibiotics/antivirals. After diagnosis of NMDAR encephalitis: plasmapheresis three times, corticosteroid 7 days, immunoglobulins 5 days followed by corticosteroid again
	Course	Day 31: patient discharged walking but mildly ataxic with prednisolone and antiepileptic treatment. Possibility of repeat immunoglobulin administration