Table 1 Summary of COVID-19 cases identified involving anti-NMDAR encephalitis with neuropsychiatric symptoms
Patient 1 | Panariello et al., 2020 [10] | Male (23Â years-old). History drug abuse |
| Â | Reason for hospitalization | Psychomotor agitation, anxiety, formal thought disorder, persecutory delusions and auditory hallucinations and global insomnia. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing |
| Â | Respiratory (other) symptoms | Fever, drop in O2 saturation, chest X-ray: bilateral milk glass opacities, chest CT: patchy bibasilar consolidation |
| Â | 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 |
| Â | Blood test | IL-6 not mentioned, no lymphopenia at anti-NMDAR encephalitis diagnosis, hyponatremia |
| Â | CSF examination | SARS-CoV-2 negative. IL-6 elevated, NMDAR-antibodies positive. Virological and microbiological diagnostics negative. Elevated red and white cells |
| Â | EEG | Theta activity, unstable, non-reactive to visual stimuli |
| Â | Therapy | Seizure prophylaxis. No symptom improvement with antipsychotics. COVID-19 therapy with hydroxychloroquine and darunavir/cobicistat. Antibiotic prophylactic therapy. After anti-NMDAR encephalitis diagnosis, dexamethasone and intravenous immunoglobulin |
| Â | Course | Clinical symptoms improved |
Patient 2 | Alvarez Bravo and Ramio, 2020 [11] | Female (30Â years-old). No previous medical history. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing |
| Â | Reason for hospitalization | Behavioral changes |
| Â | Respiratory (other) symptoms | Fever, pneumonia, thrombosis of the left iliac vein, and bilateral pulmonary embolism attributed to SARS-CoV-2 infection (Ovarian teratoma) |
| Â | Neuropsychiatric symptoms | Psychomotor agitation, paranoid ideation, dysarthria with dysprosody, and visual hallucinations, focal and generalised seizures |
| Â | Blood test | SARS-CoV-2 positive |
| Â | CSF examination | Cells count and protein elevated. SARS-CoV-2 negative, NMDAR antibodies positive. Virological and microbiological diagnostics negative |
| Â | EEG | Epileptic discharges in the left frontotemporal region |
| Â | Therapy | After anti-NMDAR encephalitis diagnosis, 5Â days of methylprednisolone and immunoglobulins administered |
| Â | Course | Hypoprosexia, emotional lability and memory disorder, Stabilised systemic and respiratory symptoms |
Patient 3 | Allahyari et al., 2021 [12] | Female (18Â years-old). No previous medical history. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing |
|  | Reason for hospitalization | Generalized tonic–clonic seizures |
| Â | Respiratory (other) symptoms | Fever, pneumonia, hypotonia, tachycardia, tachypnea, oxygen saturation of 90%, bilateral pulmonary crackles in lower lung zones, |
|  | Neuropsychiatric symptoms | 3-week history of mood change as depression and anhedonia accompanied by lack of concentration, generalized tonic–clonic seizures |
| Â | Blood test | Neutrophilia, lymphopenia, CRP normal |
| Â | CSF examination | Cells count elevated. SARS-CoV-2 positive, NMDAR antibodies positive. Virological and microbiological diagnostics negative |
| Â | EEG | Epileptic discharges in the left frontotemporal region |
| Â | Therapy | Seizure prophylaxis. COVID-19 therapy with Remdesivir, Lopinavir/Ritonavir, and Interferon b1a (Resigen). Antibiotic prophylactic therapy. After anti-NMDAR encephalitis diagnosis, methylprednisolone and intravenous immunoglobulin |
| Â | Course | After 2Â months of hospitalization discharged with full recovery |
Patient 4 | McHattie et al., 2021 [13] | Female (53Â years-old). Ductal carcinoma of breast in remission. History of depression and psoriasis. Medications: sertraline, ciclosporin |
| Â | Reason for hospitalization | 2-week confusion, fever and myalgias. SARS-CoV-2 negative on admission, positive on day-14 in nasopharyngeal swab RT-PCR testing |
| Â | Respiratory (other) symptoms | Severe hypoxemia with O2 dependency. Chest X-ray: bilateral infiltrations |
| Â | Neuropsychiatric symptoms | Day-5: catatonic symptoms of severe echolalia, palilalia, perseverations and echopraxia. Speech high-pitched and behavioural disinhibition. Left-side discrete hemiparesis, non-responsive to commands. Day-17: focal seizures, marked dysautonomia (increasingly hypotensive with bradycardia). Hyperkinetic movement disorder not present |
| Â | Blood test | CRP elevated with lymphopenia. NMDAR antibodies negative |
| Â | CSF examination | SARS-CoV-2 negative. Leukocytes high. Low glucose and high protein. Virological and microbiological diagnostics negative. NMDAR antibodies positive |
| Â | EEG | Slow activity on admission. No evidence of epileptiform discharges |
| Â | Therapy | Antiepileptic treatment. For suspected viral encephalitis, initial therapy with aciclovir and steroids. COVID-19 therapy with hydroxychloroquine, antibacterial and antifungal treatment. After anti-NMDAR encephalitis diagnosis, steroids, intravenous immunoglobulins and tocilizumab |
| Â | Course | Worsening symptoms with steroids. 1-month therapy: neuropsychiatric symptoms improved but persistence of left-side weakness. Cardiac MRI day 70: regression of signal changes. Brain MRI: atrophy of left amygdala and left hippocampus |
Patient 5 | Monti et al., 2020 [14] | Male (50Â years-old). Moderate arterial hypertension |
Reason for hospitalization | Acute psychiatric symptoms. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing | |
Respiratory (other) symptoms | None. 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 | SARS-CoV-2 not mentioned. Third lumbar puncture: NMDAR antibodies positive, cell count and IL-6 elevated. Oligoclonal bands positive. Virological and microbiological diagnostics negative | |
EEG | Diffuse delta activity with extreme delta brush pattern.Anterior subcontinuous periodic theta activity | |
Therapy | Antiepileptics and anaesthetics. COVID-19 therapy with hydroxychloroquine and lopinavir/ritonavir. After diagnosis of anti-NMDAR encephalitis: corticosteroids, immunoglobulins and plasmapheresis | |
Course | 4Â months after symptom onset patient discharged in good condition with no neuropsychiatric symptoms | |
Patient 6 | Burr et al., 2021 [15] | Female (23Â months-old). Vaccinated. No previous diseases. Family history unremarkable |
Reason for hospitalization | Fever, psychomotor agitation, sleep disturbances, constipation, decreased oral intake. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing | |
Respiratory (other) symptoms | None. Fever, dehydration present | |
Neuropsychiatric symptoms | Agitation, poor sleep, mood swings, mutism, regular kicking/ flapping 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 positive, IL-6 not mentioned | |
CSF examination | SARS-CoV-2 negative. Mild elevation of leukocytes. Oligoclonal bands negative. Virological and microbiological diagnostics negative. NMDAR antibodies positive. IL-6 not mentioned | |
EEG | Not mentioned | |
Therapy | Antiepileptics. After anti-NMDAR encephalitis diagnosis, corticosteroid therapy for 5Â days with no improvement, followed by intravenous immunoglobulin administration | |
Course | Remission within one week after immunoglobulin therapy | |
Patient 7 | Sanchez-Morales et al., 2021 [18] | Male (14Â years-old). No previous medical history. SARS-CoV-2 positive nasopharyngeal swab RT-PCR testing |
Reason for hospitalization | Behavioral 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 negative | |
CSF examination | SARS-CoV-2 positive, NMDAR antibodies positive. Virological and microbiological diagnostics negative | |
EEG | Not mentioned | |
Therapy | After anti-NMDAR encephalitis diagnosis, methylprednisolone and immunoglobulins administered | |
Course | Complete remission of neurological impairment. Control of epilepsy. Persistence of psychiatric symptoms | |
Patient 8 | Sarigecili et al., 2021 [16] | Male (7Â years-old). Vaccinated. No previous diseases. No abnormal family history |
Reason for hospitalization | 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. Virological and microbiological diagnostics negative. NMDAR antibodies positive. IL-6 not mentioned | |
EEG | Encephalopathic pattern with disseminated delta waves | |
Therapy | Antiepileptics after onset of seizures. Initial therapy with antibiotics/antivirals. After diagnosis of anti-NMDAR encephalitis: plasmapheresis three times, corticosteroid 7Â days, immunoglobulins 5Â days followed by corticosteroid again | |
Course | Day 31: patient discharged walking but mildly ataxic with prednisolone and antiepileptic treatment. Possibility of repeat immunoglobulin administration |