RARE DISEASE
NMDA receptor encephalitis
NMDA receptor encephalitis
NMDA receptor encephalitis
Synonyms: Limbic encephalitis with N-methyl-D-aspartate receptor antibodies, Limbic encephalitis with NMDA receptor antibodies, N-methyl-D-aspartate receptor encephalitis, NMDARE, anti-NMDA receptor encephalitis
Synonyms: Limbic encephalitis with N-methyl-D-aspartate receptor antibodies, Limbic encephalitis with NMDA receptor antibodies, N-methyl-D-aspartate receptor encephalitis, NMDARE, anti-NMDA receptor encephalitis
Synonyms: Limbic encephalitis with N-methyl-D-aspartate receptor antibodies, Limbic encephalitis with NMDA receptor antibodies, N-methyl-D-aspartate receptor encephalitis, NMDARE, anti-NMDA receptor encephalitis
Drug discovery
2
drugs
With orphan designations
Overview
Anti-NMDA receptor encephalitis is an autoimmune disorder mediated by IgG antibodies against the GluN1 subunit of NMDA receptors, causing synaptic dysfunction and neuropsychiatric symptoms (e.g., psychosis, seizures, dyskinesias, autonomic instability, and coma). Diagnosis requires CSF antibody testing, though MRI/EEG may support evaluation. Early immunotherapy (corticosteroids, IVIG, plasma exchange) and tumor resection (if present) improve outcomes, though recovery often spans months to years [1][4][8][17].
Population
Primarily affects young adults (median age 23–24 years) and children, with 4:1 female predominance [6][10].
Racial disparities: Higher incidence in Black (2.94/million/year), Hispanic (2.17), and Asian/Pacific Islander (2.02) vs. White individuals (0.40) [2][6].
Ovarian teratomas are identified in ~31% of cases, particularly in Black females (58%) [2][6][13].
Therapies
First-line: High-dose corticosteroids, IVIG, and plasmapheresis [3][5][17].
Second-line: Rituximab or cyclophosphamide for refractory cases [3][7][9].
Tumor-directed: Resection of ovarian teratomas improves prognosis [6][13].
- Maintenance immunosuppression (e.g., mycophenolate) is reserved for relapsing/severe cases [3][7].
Categories: rare neurological diseases
Research Papers
1,107 drug discovery papers about NMDA receptor encephalitis, with 4 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,107 drug discovery papers about NMDA receptor encephalitis, with 4 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-17 | Clinical characteristics and outcomes of patients with autoimmune encephalitis at a tertiary center in Saudi Arabia.
Autoimmune encephalitis (AE) is an important cause of subacute encephalopathy and seizure. Regional cohort-level data are limited. We aimed to characterize the clinical presentation, antibody profiles, neuroimaging findings, treatment, and outcomes of patients with AE managed at a tertiary referral center in Saudi Arabia. This single-center retrospective study included patients who fulfilled the 2016 Graus diagnostic criteria for AE. Patients were identified using the EPIC platform, and clinical, serological, magnetic resonance imaging, treatment, and modified Rankin scale data were reviewed. Among 148 patients screened, 18 met the inclusion criteria, including 12 with antibody-positive AE, 5 with seronegative limbic encephalitis (LE), and 1 with probable AE. Anti-N-methyl-D-aspartate receptor encephalitis (n=9) occurred exclusively in young women (mean 17.2 years), with orofacial dyskinesia (44.4%) and one ovarian teratoma. Two patients with anti-glutamic acid decarboxylase 65 (GAD65)-associated disease presented after 2 to 8 years with refractory status epilepticus and mesiotemporal abnormalities. One patient with dual antibdies anti-gamma-aminobutyric acid B receptor encephalitis with anti-GAD65 had small cell lung cancer. Seronegative AE (n=5, mean 40.4 years) presented acutely (<14 days) with mesiotemporal abnormalities, and all patients received pulse steroids. One patient with seronegative LE died from cyclophosphamide toxicity. At ≥3 months, 77.8% achieved a modified Rankin scale score of 0 to 2. This single-center Saudi cohort included seropositive and seronegative AE. Anti-GAD65-associated disease was characterized by delayed presentation and refractory seizures, whereas seronegative LE showed a uniform acute mesiotemporal pattern responsive to first-line immunotherapy. Outcomes were comparable with those of international cohorts, supporting early recognition and larger regional studies.
2026-08-15 | Symptom evolution, persistence, and pharmacological management in paediatric NMDA receptor antibody encephalitis.
To characterise symptom onset, progression, and persistence in paediatric N-methyl-D-aspartate receptor antibody encephalitis (NMDARE) using the Paediatric Autoimmune encephalitis Severity Scale (PASS), and to describe real-world symptomatic pharmacological management. We performed a retrospective study of children (<18 years) with confirmed NMDARE admitted to two tertiary centres (2012-2024). Disease severity was assessed using the modified Rankin Scale (mRS) and PASS at nadir, discharge, one year, and last follow-up. Symptomatic treatments and their timings, clinician-rated benefits and adverse events were recorded, with adverse event:benefit ratios calculated. Thirty-five patients were included (median age 8 years [IQR 4-13]; 71% female). Median peak severity was mRS 5 and PASS 22/30. Seizures and psychiatric manifestations were the most frequent presenting symptoms, whereas movement disorders, motor deficits, and autonomic dysfunction typically appeared later. Younger children (<12 years) presented with a more florid neurological picture, whereas older patients more often presented with psychiatric features; both groups progressed to similar multisystem severity at nadir. At one year, 68% achieved mRS 0-1 (median PASS 3/30), increasing to 87% at last follow-up (median 5 years). PASS identified persistent impairments in activities of daily living (26%), speech/communication (17%), and sleep (14%) at last follow-up. Symptom-directed treatments showed high perceived benefit across drug classes; second-generation antipsychotics were generally well tolerated, except risperidone, which showed higher adverse event rates. Persistent neurocognitive and functional deficits are common following NMDARE, captured better by PASS than mRS. Symptom-directed treatments showed overall favourable tolerability, with second-generation antipsychotics except risperidone demonstrating good safety.
2026-08-10 | [A case of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis presenting with characteristic symptoms such as altered sense of time, visual distortion and hallucinations].
A previously healthy 20-year-old woman was admitted to our hospital because of psychobehavioral alterations, generalized seizure, and post-ictal drowsiness. Six weeks before this admission, depression developed, followed by dysgeusia, anorexia, hearing loss, auditory hallucinations, logoclonia, and generalized seizures, leading to the first hospitalization. On admission, the temperature was 37°C. She was awake, well oriented, but had logoclonia. Brain MRI and electroencephalography (EEG) were both unremarkable, but cerebrospinal fluid (CSF) analysis revealed 7 cells/μl. After admission, she began to exhibit a variety of psychosomatic symptoms, such as altered sense of time, visual disturbances, visual hallucinations, and phonological paraphasia, and logoclonia. On day 4 she was once discharged home, but 4 days later, she was re-admitted to the hospital because of recurrence of seizure. An EEG recorded on day 1 revealed epileptiform discharges arising from the Cz and Pz. CSF-restricted oligoclonal bands were detected. Because of the suspicion of autoimmune encephalitis, the patient was treated with 3 cycle of intravenous high-dose methylprednisolone and 4 rounds of plasma exchanges, resulting in resolution of seizures; however, cognitive impairment and an altered sense of time persisted. Antibody test results came back positive for GluN1 (estimated CSF antibody titers, 1:4) with neuropil staining on rat brain immunohistochemistry, confirming the diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, but no myelin oligodendrocyte glycoprotein antibodies were detected. No ovarian teratoma was found. Following rituximab therapy, cognitive function improved. This case highlights that a forme fruste of anti-NMDAR encephalitis can be attributed to low titers of GluN1 antibodies, and cause a variety of psychosomatic symptoms, without development of typical spectrum of anti-NMDAR encephalitis. Careful assessment is required for appropriate diagnosis and treatment.
2026-07-31 | When mania is not primary: A case report on anti-NMDA receptor encephalitis presenting during early pregnancy
Anti-NMDA receptor encephalitis is the most common subtype of autoimmune encephalitis, predominantly affecting young females and often presenting with psychiatric symptoms, leading to diagnostic challenges. We report a 27-year-old pregnant female presenting with first-episode mania and recurrent seizures. During hospitalisation, she developed drowsiness, orofacial dyskinesia and emerging catatonia, raising suspicion of autoimmune encephalitis. Initial EEG, MRI brain and CSF studies were normal, but CSF testing later confirmed anti-NMDA receptor antibodies. She was treated with intravenous methylprednisolone followed by mycophenolate mofetil resulting in significant recovery. This case highlights the need to consider autoimmune encephalitis in new-onset psychiatric presentations with neurological features.
2026-07-30 | Lethargy With Reversible Bilateral Basal Ganglia and Substantia Nigra Lesions in Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Case Report
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a neuroinflammatory disorder characterized by a broad spectrum of neuropsychiatric symptoms, and the optimal treatment strategy for atypical or refractory cases has not been well established. We report the case of a 26-year-old woman with anti-NMDAR encephalitis associated with an ovarian teratoma who presented with acute psychiatric and neurological manifestations. The patient underwent tumor resection followed by first-line immunotherapies, including corticosteroids, intravenous immunoglobulin, and plasma exchange. Because of persistent neurological symptoms, second-line immunotherapy with cyclophosphamide was initiated, leading to gradual clinical improvement. However, she subsequently developed lethargy and upper-limb tremors, accompanied by bilateral basal ganglia and substantia nigra abnormalities on MRI. Notably, both her clinical symptoms and radiological abnormalities improved following an additional course of cyclophosphamide treatment. This report highlights a rare clinical and radiological manifestation and suggests that additional immunotherapy may be effective for delayed neurological worsening.
2026-08-17 | Clinical characteristics and outcomes of patients with autoimmune encephalitis at a tertiary center in Saudi Arabia.
Autoimmune encephalitis (AE) is an important cause of subacute encephalopathy and seizure. Regional cohort-level data are limited. We aimed to characterize the clinical presentation, antibody profiles, neuroimaging findings, treatment, and outcomes of patients with AE managed at a tertiary referral center in Saudi Arabia. This single-center retrospective study included patients who fulfilled the 2016 Graus diagnostic criteria for AE. Patients were identified using the EPIC platform, and clinical, serological, magnetic resonance imaging, treatment, and modified Rankin scale data were reviewed. Among 148 patients screened, 18 met the inclusion criteria, including 12 with antibody-positive AE, 5 with seronegative limbic encephalitis (LE), and 1 with probable AE. Anti-N-methyl-D-aspartate receptor encephalitis (n=9) occurred exclusively in young women (mean 17.2 years), with orofacial dyskinesia (44.4%) and one ovarian teratoma. Two patients with anti-glutamic acid decarboxylase 65 (GAD65)-associated disease presented after 2 to 8 years with refractory status epilepticus and mesiotemporal abnormalities. One patient with dual antibdies anti-gamma-aminobutyric acid B receptor encephalitis with anti-GAD65 had small cell lung cancer. Seronegative AE (n=5, mean 40.4 years) presented acutely (<14 days) with mesiotemporal abnormalities, and all patients received pulse steroids. One patient with seronegative LE died from cyclophosphamide toxicity. At ≥3 months, 77.8% achieved a modified Rankin scale score of 0 to 2. This single-center Saudi cohort included seropositive and seronegative AE. Anti-GAD65-associated disease was characterized by delayed presentation and refractory seizures, whereas seronegative LE showed a uniform acute mesiotemporal pattern responsive to first-line immunotherapy. Outcomes were comparable with those of international cohorts, supporting early recognition and larger regional studies.
2026-08-15 | Symptom evolution, persistence, and pharmacological management in paediatric NMDA receptor antibody encephalitis.
To characterise symptom onset, progression, and persistence in paediatric N-methyl-D-aspartate receptor antibody encephalitis (NMDARE) using the Paediatric Autoimmune encephalitis Severity Scale (PASS), and to describe real-world symptomatic pharmacological management. We performed a retrospective study of children (<18 years) with confirmed NMDARE admitted to two tertiary centres (2012-2024). Disease severity was assessed using the modified Rankin Scale (mRS) and PASS at nadir, discharge, one year, and last follow-up. Symptomatic treatments and their timings, clinician-rated benefits and adverse events were recorded, with adverse event:benefit ratios calculated. Thirty-five patients were included (median age 8 years [IQR 4-13]; 71% female). Median peak severity was mRS 5 and PASS 22/30. Seizures and psychiatric manifestations were the most frequent presenting symptoms, whereas movement disorders, motor deficits, and autonomic dysfunction typically appeared later. Younger children (<12 years) presented with a more florid neurological picture, whereas older patients more often presented with psychiatric features; both groups progressed to similar multisystem severity at nadir. At one year, 68% achieved mRS 0-1 (median PASS 3/30), increasing to 87% at last follow-up (median 5 years). PASS identified persistent impairments in activities of daily living (26%), speech/communication (17%), and sleep (14%) at last follow-up. Symptom-directed treatments showed high perceived benefit across drug classes; second-generation antipsychotics were generally well tolerated, except risperidone, which showed higher adverse event rates. Persistent neurocognitive and functional deficits are common following NMDARE, captured better by PASS than mRS. Symptom-directed treatments showed overall favourable tolerability, with second-generation antipsychotics except risperidone demonstrating good safety.
2026-08-10 | [A case of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis presenting with characteristic symptoms such as altered sense of time, visual distortion and hallucinations].
A previously healthy 20-year-old woman was admitted to our hospital because of psychobehavioral alterations, generalized seizure, and post-ictal drowsiness. Six weeks before this admission, depression developed, followed by dysgeusia, anorexia, hearing loss, auditory hallucinations, logoclonia, and generalized seizures, leading to the first hospitalization. On admission, the temperature was 37°C. She was awake, well oriented, but had logoclonia. Brain MRI and electroencephalography (EEG) were both unremarkable, but cerebrospinal fluid (CSF) analysis revealed 7 cells/μl. After admission, she began to exhibit a variety of psychosomatic symptoms, such as altered sense of time, visual disturbances, visual hallucinations, and phonological paraphasia, and logoclonia. On day 4 she was once discharged home, but 4 days later, she was re-admitted to the hospital because of recurrence of seizure. An EEG recorded on day 1 revealed epileptiform discharges arising from the Cz and Pz. CSF-restricted oligoclonal bands were detected. Because of the suspicion of autoimmune encephalitis, the patient was treated with 3 cycle of intravenous high-dose methylprednisolone and 4 rounds of plasma exchanges, resulting in resolution of seizures; however, cognitive impairment and an altered sense of time persisted. Antibody test results came back positive for GluN1 (estimated CSF antibody titers, 1:4) with neuropil staining on rat brain immunohistochemistry, confirming the diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, but no myelin oligodendrocyte glycoprotein antibodies were detected. No ovarian teratoma was found. Following rituximab therapy, cognitive function improved. This case highlights that a forme fruste of anti-NMDAR encephalitis can be attributed to low titers of GluN1 antibodies, and cause a variety of psychosomatic symptoms, without development of typical spectrum of anti-NMDAR encephalitis. Careful assessment is required for appropriate diagnosis and treatment.
2026-07-31 | When mania is not primary: A case report on anti-NMDA receptor encephalitis presenting during early pregnancy
Anti-NMDA receptor encephalitis is the most common subtype of autoimmune encephalitis, predominantly affecting young females and often presenting with psychiatric symptoms, leading to diagnostic challenges. We report a 27-year-old pregnant female presenting with first-episode mania and recurrent seizures. During hospitalisation, she developed drowsiness, orofacial dyskinesia and emerging catatonia, raising suspicion of autoimmune encephalitis. Initial EEG, MRI brain and CSF studies were normal, but CSF testing later confirmed anti-NMDA receptor antibodies. She was treated with intravenous methylprednisolone followed by mycophenolate mofetil resulting in significant recovery. This case highlights the need to consider autoimmune encephalitis in new-onset psychiatric presentations with neurological features.
2026-07-30 | Lethargy With Reversible Bilateral Basal Ganglia and Substantia Nigra Lesions in Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Case Report
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a neuroinflammatory disorder characterized by a broad spectrum of neuropsychiatric symptoms, and the optimal treatment strategy for atypical or refractory cases has not been well established. We report the case of a 26-year-old woman with anti-NMDAR encephalitis associated with an ovarian teratoma who presented with acute psychiatric and neurological manifestations. The patient underwent tumor resection followed by first-line immunotherapies, including corticosteroids, intravenous immunoglobulin, and plasma exchange. Because of persistent neurological symptoms, second-line immunotherapy with cyclophosphamide was initiated, leading to gradual clinical improvement. However, she subsequently developed lethargy and upper-limb tremors, accompanied by bilateral basal ganglia and substantia nigra abnormalities on MRI. Notably, both her clinical symptoms and radiological abnormalities improved following an additional course of cyclophosphamide treatment. This report highlights a rare clinical and radiological manifestation and suggests that additional immunotherapy may be effective for delayed neurological worsening.
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Drug Discovery Landscape
2 orphan drug designations for NMDA receptor encephalitis.
2 orphan drug designations for NMDA receptor encephalitis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Humanized one-armed monoclonal antibody | antibodies | FDA | 2022-12-29 | — | Arialys Therapeutics, Inc. |
satralizumab-mwge | antibodies | FDA | 2022-07-18 | — | Genentech, Inc. |
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