Anti-NMDA Receptor Antibody Positivity and Presentations Without Seizure, Involuntary Movement, Hypoventilation, or Tumor: A Systematic Review of the Literature
Abstract
Materials and Methods
Search
Study Selection
Data Extraction
Results
Literature Search
Case No./Author/Publication Year | Sex/Age (Years) | Duration of Illness | Initial Diagnosis/Comorbidity | Psychiatric and Cognitive Symptoms | Neurological and Motor Symptoms | Abnormal Results for CSF/MRI/EEG | Anti-NMDAR/Abnormal Serum CSF | Immunotherapy (Order of Treatment) | Time From Initial Immunotherapy Until Clinical Improvement | Immunotherapy Response |
---|---|---|---|---|---|---|---|---|---|---|
1. Zandi et al./20117 | Male/19 | 3 months | SCZ/– | Auditory hallucinations, thought disorder, grandiose delusions, deficits of recall and verbal fluency | Nil | NA/NA/NA | +/NA | PE, steroids | 3 weeks | Very much improved |
2. Suzuki et al./20118 | Female/70 | 6 months | NA/SSc | Dementia (10/30 on MMSE) | Ataxia, tremor, rigidity, muscle weakness | +/+/ NA | +/+ | Steroids, CTX | NA | Very much improved |
3. Lekoubou et al./20129 | Female/34 | 1 month | ADEM/– | Psychomotor agitation, echolalia and echopraxia, incoherent speech, delusions of persecution | Walking difficulties, disorientation, cerebellar ataxia, hemiparesis | +/+/NA | NA/+ | IVIg, steroids, RTX | <6 months | Much improved |
4. Lebon et al./201210 | Female/16 | 2 months | Primary psychotic disorder/– | Mutism, refusal to eat, infantile behavior, auditory hallucinations, incoherent speech, memory impairment, executive deficit, attention deficit | Nil | –/–/+ | +/NA | Steroids, IVIg | 9 months | Very much improved |
5. Yuan et al./201311 | Female/22 | 3 weeks | NA/– | Affective lability, grandiose thoughts, paranoid delusion, auditory and visual hallucinations, deficits of verbal fluency, visuospatial deficit, hemispatial neglect, memory impairment | Nil | +/–/+ | NA/NA (Positive in serum or CSF or both) | Steroids, IVIg, PE, RTX | 6 months | Much improved |
6. Yau et al./201312 | Female/5 | 1 week | NA/– | Fluctuating level of consciousness, mutism, impaired speech, irritability | Nil | +/–/+ | –/+ | IVIg | 1 week | Very much improved |
7. Tüzün et al./201313 | Female/42 | 2 weeks | NA/– | Mild Executive Deficit | Double vision, difficulty walking, limited vertical gaze | +/+/– | +/+ | Steroids | 2 months | Very much improved |
8. Leypoldt et al./201314 | Male/24 | 1 day | Relapse of HSVE/– | Mania, irritability, racing thoughts, pressured speech, memory impairment, attention deficit | Nil | +/+/– | +/+ | Steroids | 1 week | Much improved |
9. Kayser et al./20135 | Male/19 | 2–3 months | Demyelinating disease/– | Aggression, excessive eye blinking, grandiosity, delusional thinking | Nil | +/+/– | +/NA | Steroids, AZA | 9 months | Very much improved |
10. Kayser et al./20135 | Female/20 | NA | NA/– | Delusion, depression | Nil | +/+/NA | +/+ | Steroids, IVIg, RTX, MMF | NA | Very much improved |
11. Kuppuswamy et al./201415 | Male/35 | 2 weeks | Primary psychotic disorder/– | Depression, suicidality, grandiosity, impulsivity, mutism, posturing, staring, ambitendency | Nil | –/–/– | +/+ | Steroids, PE, AZA | 4 months | Very much improved |
12. Finke et al./201416 | Male/67 | 2 weeks | HaNDL/– | Confusion, agitation, aggressiveness, retrograde amnesia, memory impairment, attention deficit | Transient hemiparesis, transient aphasia | +/–/+ | –/+ | Steroids, PE, AZA | 6 weeks | Much improved |
13. Byrne et al./201417 | Male/4 | 2 days | NA/– | Confusion, agitation | Dysphasia, coma | –/+/+ | +/NA | Steroids | 4 days | Very much improved |
14. Takeda et al./201418 | Male/35 | 6 days | Herpes encephalitis/– | Delirium, violent behavior, delusions, disorientation | Diplopia, paraparesis, hypoesthesia, ptosis | +/+/NA | NA/+ | Steroids, PE, CTX | 12 months | Much improved |
15. Fleischmann et al./201519 | Female/37 | 5.5 years | NA/MS and SS | Delusions, bizarre behavior, aggressiveness, memory impairment, Dementia (14/30 on MMSE), disorientation, executive deficit | Gait ataxia, dysarthria | +/+/ NA | +/+ | Steroids, AZA, CTX, NTL, PE, MTX | Nonresponse | Death (urosepsis) |
16. Cuende et al./201520 | Female/61 | 3 months | NA/RA | Memory loss | Dizziness, unsteady gait, muscle weakness, speech problems | +/–/NA | +/+ | IVig | NA | Very much improved |
17. Kruse et al./201521 | Female/14 | NA | NA/– | Anxiety, depressed mood, disinhibited and disorganized behavior, reduced verbal output, slow speech, learning difficulty | Transient arm numbness, difficulty with complex motor tasks | +/–/+ | –/+ | NA | NA | Very much improved |
18. Sühs et al./201522 | Female/23 | 2 years | Psychiatric disorder/– | Fearful behavior, stereotypical repetitive movements, loss of orientation, memory impairment, executive deficit | Nil | +/–/+ | +/NA | Steroids | 1 month | Very much improved |
19. Orengo et al./201523 | Female/29 | 3 months | NA/serum aquaporin-4 antibody positive | Anorexia, abulia, mutism, immobility, nonsensical speech, memory impairment | Imbalance and vertigo, facial numbness, ataxia | +/+/NA | –/+ | Steroids, PE, RTX | NA | Much improved |
20. Gahr et al./201524 | Male/34 | 1 week | Psychotic mania/– | Impulsivity, aggressiveness, hostility, dysphoric mania paranoid ideation hyper-religiosity | Nil | +/+/NA | +/+ | Steroids, IVIg | NA | Very much improved |
21. Senda et al./Epub ahead of print 20156 | Female/33 | 2 years | SCZ/HT | Auditory and visual hallucination, delusions of persecution, delusion of control agitation, memory impairment, executive deficit | Nil | –/–/– | NA/+ | Steroids, IVIg | 3 months | Much improved |
22 Lalanne et al./201525 | Female/31 | NA | Psychotic depression | Melancholia, depression, cenesthopathy, memory impairment, attention deficit | Nil | NA/+/+ | NA/+ | Steroids, IVIg | 5 weeks | Very much improved |
Clinical Characteristics
Test Results
Immunotherapy and Outcome
Discussion
Diversity of Clinical Characteristics
Response to Immunotherapy
Detection of Anti-NMDAR Antibodies
Definition of Atypical Presentations
Conclusions
References
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Competing Interests
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