Top

Published in:

01-11-2020 | Cranial MRI | Original Article

Anti-N-methyl-D-aspartate receptor encephalitis: a prospective study focused on cerebrospinal fluid and clinical symptoms

Authors: Shouyi Wu, Huiqin Li, Yajun Lian, Yuan Chen, Yake Zheng, Chengze Wang, Qiaoman Zhang, Zhi Huang, Zhengrong Mao, Kai Pang

Published in: Neurological Sciences | Issue 11/2020

Abstract

Background and objective

To analyze the relationship between brain MRI, clinical symptoms, and cerebrospinal fluid (CSF) and to provide a reference for early diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.

Materials and Methods

A total of 62 patients with anti-NMDAR encephalitis in Zhengzhou, China (2016–2018) were observed and registered prospectively. First, we analyzed the characteristics of clinical symptoms. Second, according to the disease duration, patients were divided into two groups, and then we analyzed the CSF features. In addition, they were divided into two groups according to the brain MRI, and then the CSF features were analyzed. Finally, the characteristics of cerebrospinal fluid in patients with seizure as the initial symptom were analyzed.

Results

Seizure presents as the initial symptom in 14 patients (22.5%), including 11 males (78.57%). The proportion and concentration of CSF total protein abnormalities in the early stage group were significantly higher than those in the middle and late group (P < 0.05). The total protein concentration in the abnormal brain MRI group was significantly higher than that in the normal MRI group (P < 0.05).

Conclusion

Anti-NMDAR encephalitis should be suspected, when male patients complain of seizure as an initial symptom and have simultaneously had headaches or fever prior to onset. The sensitivity of anti-NMDAR antibody is higher in CSF than in serum. Total CSF protein is more prone to elevation in the middle and late stages of anti-NMDAR encephalitis. Brain MRI abnormalities with anti-NMDAR encephalitis are related to the total protein concentration of CSF, which may be related to the disease duration.

Available only for authorised users

Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, Dessain SK, Rosenfeld MR, Balice-Gordon R, Lynch DR (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7:1091–1098. https://doi.org/10.1016/S1474-4422(08)70224-2CrossRefPubMedPubMedCentral

Armangue T, Titulaer MJ, Málaga I, Bataller L, Gabilondo I, Graus F, Dalmau J, Spanish Anti-N-methyl-D-Aspartate Receptor (NMDAR) Encephalitis Work Group (2013) Pediatric anti-N-methyl-D-aspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients. J Pediatr 162:850–856. https://doi.org/10.1016/j.jpedsCrossRefPubMed

Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Höftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Prüss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostásy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, Dalmau J (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15:391–404. https://doi.org/10.1016/S1474-4422(15)00401-9CrossRefPubMedPubMedCentral

Titulaer MJ, McCracken L, Gabilondo I et al (2013) Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis:an observational cohort study. Lancet Neurol 12:157–165. https://doi.org/10.1016/S1474-4422(12)70310-1CrossRefPubMedPubMedCentral

Wang R, Guan HZ, Ren H, Wang W, Hong Z, Zhou D (2015) CSF findings in patients with anti-N-metIlyl-D-aspartate receptor-encephalitis. Seizure 29:137–142. https://doi.org/10.1016/j.seizure.2015.04.005CrossRefPubMed

Deng B, Chen XJ, Li X et al (2016) Analysis of the cerebrospinal fluid abnormalities and their correlation with disease course in patients with anti-N-methyl-D-aspartate receptor encephalitis. Chin J Clin Neurosci 24:528–534

Gastaldi M, Zardini E, Leante R et al (2017) Cerebrospinal fluid analysis and the determination of oligoclonal bands. Neurol Sci 38:217–224. https://doi.org/10.1007/s10072-017-3034-2CrossRefPubMed

Malter MP, Elger CE, Surges R (2013) Diagnostic value of CSF findings in antibody associated limbic and anti-NMDAR-encephalitis. Seizure 22:136–140. https://doi.org/10.1016/j.seizure.2012.12.013CrossRefPubMed

Reiber H (1998) Cerebrospinal fluid--physiology, analysis and interpretation of protein patterns for diagnosis of neurological diseases. Mult Scler 4:99–107. https://doi.org/10.1177/135245859800400302CrossRefPubMed

10.

Freedman MS, Thompson EJ, Deisenhammer F, Giovannoni G, Grimsley G, Keir G, Öhman S, Racke MK, Sharief M, Sindic CJM, Sellebjerg F, Tourtellotte WW (2005) Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement. Arch Neurol 62:865–870. https://doi.org/10.1001/archneur.62.6.865CrossRefPubMed

11.

Zuliani L, Zoccarato M, Gastaldi M et al (2017) Diagnostics of autoimmune encephalitis associated with antibodies against neuronal surface antigens. Neurol Sci 38:225–229. https://doi.org/10.1007/s10072-017-3032-4CrossRefPubMed

12.

Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R (2011) Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 10:63–74. https://doi.org/10.1016/S1474-4422(10)70253-2CrossRefPubMedPubMedCentral

13.

Viaccoz A, Desestret V, Ducray F et al (2014) Clinical specificities of adult male patients with NMDA receptor antibodies encephalitis. Neurology 82:556–563. https://doi.org/10.1093/cid/cir1038CrossRefPubMed

14.

Woolley CS, McEwen BS (1994) Estradiol regulates hippocampal dendritic spine density via an N-methyl-D-aspartate receptor dependent mechanism. J Neurosci 14:7680–7687CrossRef

15.

Lynch JJ 3rd, Shek EW, Castagne V, Mittelstadt SW (2010) The proconvulsant effects of leptin on glutamate receptor mediated seizures in mice. Brain Res Bull 82:99–103. https://doi.org/10.1016/j.brainresbull.2010.02.003CrossRefPubMed

16.

Pennell PB (2009) Hormonal aspects of epilepsy. Neurol Clin 27:941–965. https://doi.org/10.1016/j.ncl.2009.08.005CrossRefPubMedPubMedCentral

17.

Kalkbrenner KA, Standley CA (2003) Estrogen modulation of NMDA-induced seizures in ovariectomized and non-ovariectomized rats. Brain Res 964:244–249. https://doi.org/10.1016/s0006-8993(02)04065-9CrossRefPubMed

18.

Wang Y, Xueqiang H, Xueping Z et al (2013) The clinical significance of cerebrospinal fluid oligoclonal bands for multiple sclerosis. Chin J Neuroimmunol 20:153–155

19.

Dalmau J, Graus F (2018) Antibody-mediated encephalitis. N Engl J Med 378:840–851. https://doi.org/10.1056/NEJMra1708712CrossRefPubMed

20.

Steiner J, Walter M, Glanz W, Sarnyai Z, Bernstein HG, Vielhaber S, Kästner A, Skalej M, Jordan W, Schiltz K, Klingbeil C, Wandinger KP, Bogerts B, Stoecker W (2013) Increased prevalence of diverse N -methyl-D-aspartate glutamate receptor antibodies in patients with an initial diagnosis of schizophrenia: specific relevance of IgG NR1a antibodies for distinction from N-methyl-D-aspartate glutamate receptor encephalitis. JAMA Psychiatry 70:1–8. https://doi.org/10.1001/2013.jamapsychiatry.86CrossRef

21.

Zerche M, Weissenborn K, Ott C, Dere E, Asif AR, Worthmann H, Hassouna I, Rentzsch K, Tryc AB, Dahm L, Steiner J, Binder L, Wiltfang J, Sirén AL, Stöcker W, Ehrenreich H (2015) Preexisting serum autoantibodies against the NMDAR subunit NR1 modulate evolution of lesion size in acute ischemic stroke. Stroke 46:1180–1186. https://doi.org/10.1161/STROKEAHA.114.008323CrossRefPubMed

22.

Busse S, Busse M, Brix B, Probst C, Genz A, Bogerts B, Stoecker W, Steiner J (2014) Seroprevalence of N-methyl-D-aspartate glutamate receptor (NMDA-R) autoantibodies in aging subjects without neuropsychiatric disorders and in dementia patients. Eur Arch Psychiatry Clin Neurosci 264:545–550. https://doi.org/10.1007/s00406-014-0493-9CrossRefPubMed

23.

Dahm L, Ott C, Steiner J, Stepniak B, Teegen B, Saschenbrecker S, Hammer C, Borowski K, Begemann M, Lemke S, Rentzsch K, Probst C, Martens H, Wienands J, Spalletta G, Weissenborn K, Stöcker W, Ehrenreich H (2014) Seroprevalence of autoantibodies against brain antigens in health and disease. Ann Neurol 76:82–94. https://doi.org/10.1002/ana.24189CrossRefPubMed

24.

Titulaer MJ, Hoftberger R, Iizuka T et al (2014) Overlapping demyelinating syndromes and anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol 75:411–428. https://doi.org/10.1002/ana.24117CrossRefPubMedPubMedCentral

25.

Dalmau J, Rosenfeld MR (2008) Paraneoplastic syndromes of the CNS. Lancet Neurol 7:327–340. https://doi.org/10.1016/S1474-4422(08)70060-7CrossRefPubMedPubMedCentral

26.

Dalmau J, Tüzün E, Wu HY, Masjuan J, Rossi JE, Voloschin A, Baehring JM, Shimazaki H, Koide R, King D, Mason W, Sansing LH, Dichter MA, Rosenfeld MR, Lynch DR (2007) Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 61:25–36. https://doi.org/10.1002/ana.21050CrossRefPubMedPubMedCentral

Title: Anti-N-methyl-D-aspartate receptor encephalitis: a prospective study focused on cerebrospinal fluid and clinical symptoms
Authors: Shouyi Wu
Huiqin Li
Yajun Lian
Yuan Chen
Yake Zheng
Chengze Wang
Qiaoman Zhang
Zhi Huang
Zhengrong Mao
Kai Pang
Publication date: 01-11-2020
Publisher: Springer International Publishing
Keywords: Cranial MRI
Anti-NMDA Receptor Encephalitis
Intracranial Hypertension
Autoimmune Encephalitis
Encephalitis
Published in: Neurological Sciences / Issue 11/2020
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-020-04451-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Anti-N-methyl-D-aspartate receptor encephalitis: a prospective study focused on cerebrospinal fluid and clinical symptoms

Abstract

Background and objective

Materials and Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background and objective

Materials and Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 11/2020

Incidence of stroke among Saudi population: a systematic review and meta-analysis

Tarlov’s cyst as an underestimated cause of persistent genital arousal disorder: a case report and review

Effects of 2-year treatment with dimethyl fumarate on cognition and functional impairment in patients with relapsing remitting multiple sclerosis

Dysphagia in neurological diseases: a literature review

Clinical RoPE (cRoPE) score predicts patent foramen ovale detection among stroke patients: a multicenter observational study

Muscle echo intensity of abdominal wall in Parkinson’s disease and healthy controls: a cross sectional study