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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 11  |  Issue : 2  |  Page : 30-36

Clinical profile of autoimmune encephalitis: Hospital-based study


Department of Neurology, Gauhati Medical College and Hospital, Guwahati, Assam, India

Date of Submission23-Jul-2021
Date of Acceptance27-Jul-2021
Date of Web Publication05-Oct-2021

Correspondence Address:
Dr. Satish Bawri
A2, Crishna Caveri, GMCH Road Ghy-05, Guwahati 781007, Assam
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ajoim.ajoim_2_21

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  Abstract 

Background: Autoimmune encephalitis causes subacute deficits of memory and cognition, often followed by suppressed level of consciousness or coma. It is a difficult clinical situation due to the similarities in the clinical, imaging, and laboratory findings with many forms of other encephalitides. Materials and Methods: The aim of this article is to study the clinical profile of autoimmune encephalitis. This is a prospective observational study and conducted from August 2014 to July 2017 at Gauhati Medical College, Guwahati. Detailed neurological evaluation along with investigation was done in all the patients. Results and Observation: All patients are diagnosed and categorized as per diagnosis criteria led done by Graus et al. A total of 18 patients were included among which 13 (72%) patients were definite, 3 (16.66%) on probable, and 2 (11%) were possible. Out of the 18 patients, 8 (44%) were males and 10 (56%) were females. The average mean age was 31 ± 4 years and the duration of symptom was 7 weeks ± 4 days. Most common findings were psychiatric symptoms 16 (89%), cognitive decline and short-term memory loss 15 (83%), seizure 14 (78%), movement disorders (hyperkinetic) 13(72%), speech abnormalities 12 (67%), and autonomic dysfunction 4 (22%). Baseline investigations and cerebrospinal fluid analysis revealed pleocytosis along with neural autoantibodies positive in 13 (72%) patients. Electroencephalogram showed epileptiform discharges along with slowing. Magnetic resonance imaging is done in every patient and consistent with the finding of autoimmune encephalitis. Discussion and Conclusion: In the present study, patients presented with varied clinical features with positive neural autoantibodies. A broad approach to testing for infectious diseases and various autoantibodies can lead to the correct diagnosis.

Keywords: Autoimmune encephalitis, immunotherapy, neural autoantibodies


How to cite this article:
Bawri S, Goswami M, Kayal AK, Das M. Clinical profile of autoimmune encephalitis: Hospital-based study. Assam J Intern Med 2021;11:30-6

How to cite this URL:
Bawri S, Goswami M, Kayal AK, Das M. Clinical profile of autoimmune encephalitis: Hospital-based study. Assam J Intern Med [serial online] 2021 [cited 2021 Oct 18];11:30-6. Available from: http://www.ajimedicine.com/text.asp?2021/11/2/30/327516


  Introduction Top


Encephalitis is characterized by inflammation of brain probably because of direct infection, a post-infectious process, or a non-infectious condition such as autoimmune encephalitis.[1] In the past 10 years, advance research gives clues of new syndromes and biomarkers that have transformed the diagnostic approach and helps in the diagnosis of autoimmune encephalitis. Autoimmune encephalitis is categorized into three groups: (1) definite, (2) probable, and (3) possible.[2],[3]

Aim of the study

The aim of the article was to study the clinical profile of autoimmune encephalitis.


  Materials and Methods Top


Inclusion criteria

All patients irrespective of age and sex present with features suggestive of encephalitis.

Exclusion criteria

Patients with tumors, trauma, diagnosed, bacterial, fungal, and viral meningoencephalitis were excluded.

It was a prospective observational study at Gauhati Medical College, Guwahati, Assam. It was conducted from August 2014 to July 2017. Detailed neurological evaluation along with routine blood, liver function test (LFT), renal function test (RFT), electrolytes, Venereal Disease Research Laboratory (VDRL) test, human immunodeficiency virus (HIV), antinuclear antibody (ANA), and chest X-ray (CXR) were done in every patient. The cerebrospinal fluid (CSF) study consisted of total count including differential count, sugar, protein, acid fast bacilli (AFB) stain, Gram’s stain, fungal stain, adenosine deaminase (ADA), VDRL, cryptococcal antigen polymerase chain reaction (PCR) for herpes simplex virus (HSV), tuberculosis (TB), Japanese encephalitis (JE), and neural autoantibodies, done in every patient. Electroencephalograph (EEG) and magnetic resonance imaging (MRI) were done in every patient of the study.


  Results and Observation Top


A total of 18 patients were included, among which 13 (72%) patients were definite, 3 (17%) on probable, and 2 (11%) were possible. [Table 1] showed the age distribution of the patients of the study. Out of the 18 patients, 8 (44%) were males and 10 (56%) were females [Figure 1]. The average mean age of patients was 31 ± 4 years. The average mean duration of symptom was 7 weeks ± 4 days. Among the 18 patients studied, the most common findings were psychiatric symptoms 16 (89%), cognitive decline and short-term memory loss 15 (83%), seizure 14 (78%), movement disorders (hyperkinetic) 13 (72%), speech abnormalities 12 (67%), and autonomic dysfunction 4 (22%) [Table 2]. Baseline routine blood along with LFT, RFT, and electrolytes was normal. ANA was positive in 2 (11%) patients. CXR showed increased bronchopulmonary vascular marking in 2 of 18 (11%) patients, fibrotic band in the left upper zone in 3 of 18 (17%) patients, and no abnormality detected in 13 of 18 (72%) patients. CSF analysis revealed pleocytosis (more than 5 cells/mm3) with low-to-normal sugar and normal-to-high protein with normal ADA, non-reactive VDRL, cryptococcal antigen, negative PCR for HSV, TB, and JE. Neural autoantibodies present in 13 patients [N-methyl-D-aspartate receptor (NMDAR)-positive in 12 patients and voltage-gated potassium channel (VGKC) complex antibodies positive in 1 patient]. Other antibodies are negative [Table 3]. EEG of the patients showed generalized epileptiform discharge pattern, diffuse cortical dysrrthymia in the form of slowing, right temporo-parietal epileptiform discharge pattern with secondary generalization and generalized theta slowing ([Figure 2] – EEG finding of one of the patients). MRI brain done in every patients of the study and consistent with the finding of the autoimmune encephalitis and some of the findings mentioned in [Figure 3]A-C, [Figure 4]A-C, and [Figure 5]A and B. Patients were started with Inj. methylprednisolone pulse dose (1 g/day) followed by oral steroid with tapering doses up to 3 months in 15 patients, Inj. methylprednisolone pulse dose (1 g/day) followed by Inj. rituximab in 3 patients. Out of the 18 patients, 17 (94%) patients improved and 1 (6%) patient in the definite autoimmune encephalitis group succumbed due to super-refractory seizures and aspiration pneumonitis.
Table 1: Age distribution of patients according to gender

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Figure 1: Sex distribution of patients

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Table 2: Most common findings of the studied patients

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Table 3: CSF finding of patients

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Figure 2: A. EEG of the patients showing spontaneous intermittent high amplitude, generalized spike, and sharp discharge pattern (before treatment). B. Intermittent generalized theta slowing with epileptiform-like discharge pattern at places (after treatment)

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Figure 3: (A-C) MRI shows T2 and FLAIR (fluid-attenuated inversion recovery) hyper-intensities in left temporoparietal extending to insular cortex and medial temporal lobe

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Figure 4: (A-C) MRI shows T2 and FLAIR hyper-intensities in right medial temporal lobe, hypothalamus, and possible involvement of left medial temporal lobe

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Figure 5: (A and B) MRI shows T2 and FLAIR hyper-intensities in bilateral temporal lobe involving left hippocampus

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  Discussion Top


Autoimmune encephalitis causes subacute deficits of memory and cognition, often followed by the suppressed level of consciousness or coma. It is a difficult clinical situation due to the similarities in the clinical, imaging, and laboratory findings with many forms of other encephalitides.[4],[5] Advance research transformed the diagnostic approach of autoimmune encephalitis and categorized into three groups: (1) definite, (2) probable, and (3) possible, as done by Graus et al.[2] in the position paper.

In the absence of evidence of brain inflammation, an abnormality in the CSF and in brain neuroimaging helps to point toward non-infectious etiology.[3] Both antibody status and use of the response to immunotherapy as diagnostic criteria are not used for diagnosis of autoimmune encephalitis as, first, antibody testing is not readily accessible and results can take unusual long time and secondly, immunotherapy is not available at the time of symptom onset or early clinical evaluation.[2] Neural autoantibodies are associated with a spectrum of clinical features and relative response to immunotherapy and are calculated into three groups: (i) synaptic receptor or cell surface, (ii) synaptic antigen (intracellular), and (iii) onconeuronal antigen (intracellular).[6],[7] Differences are summarized in [Table 4].
Table 4: Neural autoantibodies (intracellular vs. cell surface antigens)

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Altered sensorium, sleep disturbances, abnormal movement, and seizures are some of the key features of autoimmune encephalitis. Seizures in autoimmune encephalitis may be focal or generalized and are often multifocal.

Diagnostic criteria for anti-NMDA receptor autoimmune encephalitis are mentioned by the position paper by Graus et al.[2]

Probable*

All three criteria met:

  1. Rapid onset (<3 months) of four of the six following major groups of symptoms:
    • Abnormal (psychiatric) behavior or cognitive dysfunction
    • Speech dysfunction (pressured speech, verbal reduction, and mutism)
    • Seizures
    • Movement disorder, dyskinesias, or rigidity/abnormal postures
    • Decreased level of consciousness
    • Autonomic dysfunction or central hypoventilation
  2. At least one of the following laboratory study results:
    • Abnormal EEG (focal or diffuse slow or disorganized activity, epileptic activity, or extreme delta brush)
    • CSF with pleocytosis or oligoclonal bands
  3. Reasonable exclusion of other disorders.


Also the presence of the three of the above groups of symptoms accompanied by a systemic teratoma also led to diagnosis of probable autoimmune encephalitis

Definite*

Diagnosis can be made in the presence of one or more of the six major groups of symptoms, antibodies**, and after reasonable exclusion of other disorders.

• Patients with a history of herpes simplex encephalitis (HSE) in the previous weeks might have relapsing immune-mediated neurological symptoms (post-HSE).

•• Antibody testing should include testing of CSF. If only serum is available, confirmatory tests should be included (e.g., live neurons or tissue immunohistochemistry, in addition to cell-based assay).

Possible

Diagnosis can be made when all three of the following criteria have been met:

  1. Rapid onset (<3 months) of working memory deficits (short-term memory loss), altered mental status*, or psychiatric symptoms.
  2. At least one of the following:
    • New focal central nervous system (CNS) findings
    • Seizures not explained by a previously known seizure disorder
    • CSF pleocytosis (white blood cell count of more than 5 cells/mm³)
    • MRI features**
  3. Reasonable exclusion of alternative causes


• Altered mental status defined as decreased or altered level of consciousness, lethargy, or personality change.

• • Brain MRI hyperintense signal on T2-weighted and FLAIR sequences highly restricted to one or both medial temporal lobes, or in multifocal areas involving gray matter, white matter, or both compatible with demyelination or inflammation.[8],[9]

Among the 18 patients studied, most common combined presentation of the patients was psychiatric symptoms along with seizure in 16 (89%) patients, psychiatric symptoms along with hyperkinetic movement in 14 (78%) patients, seizures along with hyperkinetic movement in 13 (72%) patients, altered sensorium, seizure, and hyperkinetic movement in 11 (61%) patients, and psychiatric symptoms and speech abnormalities along with hyperkinetic movement in 6 (33%) patients [Table 5].
Table 5: Most common combined presentation of the patients

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EEG is suggestive of epileptiform-like discharge pattern and neural autoantibodies (NMDAR antibodies in 12 patients and VGKC-complex antibodies in 1 patient and other antibodies are negative) in CSF analysis. Out of the 18 patients, 6 (5 patients in the definite group and 1 patient in the probable group) patients have ovarian teratoma and 2 patients have small cell carcinoma of lungs. Patients were started with antiepileptic, intravenous methylprednisolone, antipsychotic, and other supportive treatment. Out of the 18 patients, subsequent intravenous immunoglobulin (IvIg) in 3 patients, plasma paresis in 2 patients and injection rituximab in 2 patients were considered. Seizure was not controlled in 5 out of 18 patients and subsequent 3 antiepileptics were considered (1 patient out of these 3 patients needs addition of fourth antiepileptic for focal seizure). Out of the 18 patients, 10 patients were put on ventilators and average stay on ventilator was 2 weeks ± 3 days, of which 1 patient succumbed due to aspiration pneumonia and super-refractory seizures.

In the study by Vitaliani et al.,[10] anti-NMDA receptor autoimmune encephalitis is presented as syndrome of encephalitis, psychiatric symptoms, hypoventilation and associated with ovarian teratoma.

In the study by Dalmau et al.,[11] anti-NMDA receptor autoimmune encephalitis is reported in all ages, most common in the age range 18–35 years (Female>Male), and 20–60% have a tumor and also reported after HSE. Tremor, writhing, rigidity, abnormal eye movements, abnormal posture, elaborate motions of arms and legs presented as abnormal movement, and atypical features such as hemiparesis and cerebellar ataxia were also seen more common in children. In 2009, Florance et al.[12],[13] reported that one-third of the patients have abnormal movements such as ataxia, chorea, dystonia, myoclonus, or tremors.

In the study by Irani et al.,[14] VGKC receptor autoimmune encephalitis presented as limbic encephalitis (amnesia, confusion, neuropsychiatric disturbance, seizures), acquired neuromyotonia (peripheral nerve hyperexcitability, muscle cramps and stiffness, slow relaxation, twitching), Morvan’s syndrome (neuromyotonia, autonomic dysfunction, insomnia) and associated with <20% tumor of thymoma and lung. In the same year, Malter et al.[15] describe that seizures and movement disorder are shown to be highly refractory to immunotherapy. Hacohen et al.[12],[16] in 2013 reported that psychiatry symptoms vary from mood swings to fulminant psychosis in 50% of the autoimmune encephalitis patients.

Determination of “VGKC-complex antibodies” should be complemented with molecular characterization of the antigens (LGI1, Caspr2, unknown). While antibodies to LGI1 or Caspr2 have syndrome specificity and the associated symptoms often respond to immunotherapy, antibodies to unknown antigens lack syndrome specificity and the response to immunotherapy is less predictable.[17]

Autoimmune encephalitis in children has different clinical presentations due to neuronal circuit’s evolution, neuroreceptor densities, and myelination because of normal development. Prognosis of autoimmune encephalitis has considerable outcome from patients of severe impairment with noticeable improvements over the period of 1–2 years. Relapses are seen in 57%, and long-term (> 1 year) maintenance immunotherapy was required in 81%.[18],[19]


  Conclusion Top


One of the treatable causes of acute encephalitis is autoimmune encephalitis. Although diagnosis is a bit challenging but with the help of combination of clinical history and supportive investigation, diagnosis of autoimmune encephalitis can be made. Autoimmune encephalitis needs to be recognized early as treatment delays worsen prognosis and increase the chance of permanent neurological deficits.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Lancaster E . The diagnosis and treatment of autoimmune encephalitis. J Clin Neurol 2016;12:1-13.  Back to cited text no. 1
    
2.
Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391-404.  Back to cited text no. 2
    
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Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: Consensus statement of the International Encephalitis Consortium. Clin Infect Dis 2013;57:1114-28.  Back to cited text no. 3
    
4.
Sejvar JJ, Kohl KS, Bilynsky R, Blumberg D, Cvetkovich T, Galama J, et al; Brighton Collaboration Encephalitis Working Group. Encephalitis, myelitis, and acute disseminated encephalomyelitis (ADEM): Case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine 2007;25:5771-92.  Back to cited text no. 4
    
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Bloch KC, Glaser C. Diagnostic approaches for patients with suspected encephalitis. Curr Infect Dis Rep 2007;9:315-22.  Back to cited text no. 5
    
6.
Bera KD, Vincent A, Irani SR, et al. Autoimmune encephalitis—Antibody targets and their potential pathogenicity in immunotherapy-responsive syndromes. US Neurol 2013;9:55-60.  Back to cited text no. 6
    
7.
Rosenfeld MR, Titulaer MJ, Dalmau J. Paraneoplastic syndromes and autoimmune encephalitis. Neurol Clin Pract2012;2:215-23.  Back to cited text no. 7
    
8.
Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis: Neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000;123:1481-94.  Back to cited text no. 8
    
9.
Graus F, Delattre JY, Antoine JC, Dalmau J, Giometto B, Grisold W, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004;75:1135-40.  Back to cited text no. 9
    
10.
Vitaliani R, Mason W, Ances B, Zwerdling T, Jiang Z, Dalmau J. Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma. Ann Neurol 2005;58:594-604.  Back to cited text no. 10
    
11.
Dalmau J, Tüzün E, Wu H-y, Masjuan J, Rossi JE, Voloschin A . Paraneoplastic anti–N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007;61:25-36.  Back to cited text no. 11
    
12.
Cellucci T, Van Mater H, Graus F, Muscal E, Gallentine W, Klein-Gitelman MS. Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient. Neurol Neuroimmunol Neuroinflamm 2020;7:e663.  Back to cited text no. 12
    
13.
Florance NR, Davis RL, Lam C, Szperka C, Zhou L, Ahmad S, et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009;66:11-8.  Back to cited text no. 13
    
14.
Irani SR, Alexander S, Waters P, Kleopa KA, Pettingill P, Zuliani L. Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia. Brain 2010:133;2734-48.  Back to cited text no. 14
    
15.
Malter MP, Helmstaedter C, Urbach H, Vincent A, Bien CG. Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol 2010;67:470-8.  Back to cited text no. 15
    
16.
Hacohen Y, Wright S, Waters P, Agrawal S, Carr L, Cross H, et al. Paediatric autoimmune encephalopathies: Clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry 2013;84:748-55.  Back to cited text no. 16
    
17.
Lai M, Huijbers MG, Lancaster E, Graus F, Bataller L, Balice-Gordon R, et al. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: A case series. Lancet Neurol 2010;9:776-85.  Back to cited text no. 17
    
18.
Flanagan EP, McKeon A, Lennon VA, Boeve BF, Trenerry MR, Tan KM, et al. Autoimmune dementia: Clinical course and predictors of immunotherapy response. Mayo Clin Proc 2010;85:881-97.  Back to cited text no. 18
    
19.
Flanagan EP, Caselli RJ. Autoimmune encephalopathy. Semin Neurol 2011;31:144-57.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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