Atypical Association of Autoimmune Limbic Encephalitis with Anti-NMDA Receptor Antibodies in a Young Male Patient: Clinical, Imaging, and Neuropsychological Characteristics

The spectrum of autoimmune encephalitis (AE) encompasses several entities characterized by a variable frequency of psychiatric symptoms, cognitive dysfunction, focal deficits, and seizures. Although patients with AE can be categorized in specific syndromes, overlapping manifestations are also common. Furthermore, atypical correlations between clinical phenotypes and autoantibody profiles could occur in rare cases. Here, we report the rare case of a young adult man attending due to new-onset seizures and a history of memory loss, autonomic disturbances, headache, behavioral changes, and visual and olfactory hallucinations. The patient was subjected to a complete diagnostic approach that included a comprehensive laboratory workup, neuropsychological testing, electroencephalogram, cerebrospinal fluid (CSF) analysis, brain MRI, and positron emission tomography/computed tomography scan that revealed a functional and structural compromise of the bilateral medial temporal lobes. Together with the clinical manifestations of the patient, these findings were compatible with the diagnosis of autoimmune limbic encephalitis (ALE). Strikingly, further analysis of the CSF showed autoantibodies against the N-methyl-D-aspartate (NMDA) receptor. We found very few cases of the co-occurrence of anti-NMDA receptor antibodies and nonparaneoplastic ALE in the literature, especially in male patients. Our report exemplifies the complicated differential diagnosis of ALE and adds clinical information of the association with anti-NMDA receptor antibodies.

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Anti-N-Methyl-D-Aspartate Encephalitis as Paraneoplastic Manifestation of Germ-Cells Tumours: A Cases Report and Literature Review

Case Reports in Immunology ◽

10.1155/2019/4762937 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Claudia Geraldine Rita ◽

Israel Nieto Gañan ◽

Adriano Jimenez Escrig ◽

Ángela Carrasco Sayalero

Keyword(s):

Nmda Receptor ◽

Germ Cell ◽

Germ Cells ◽

Germ Cell Tumour ◽

Clinical Manifestations ◽

Autoimmune Encephalitis ◽

Cell Tumour ◽

Ovarian Teratoma ◽

Surgical Removal ◽

Receptor Antibodies

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is the most common form of autoimmune encephalitis, caused by the interaction between an antibody and its target, located on glutamate receptor type N-methyl-D-aspartate (NMDA) of neuronal surface. There is a wide spectrum of clinical features starting by a viral-like prodrome, followed by symptoms such as psychosis, aggressive behaviour, memory loss, seizures, movement disorders, and autonomic instability. Up to 50% of the affected young female patients have germ-cells tumours as ovarian teratoma, making it essential to establish an early diagnosis through detection of specific antibodies in serum and cerebrospinal fluid (CSF). This retrospective observational study was performed in patients whom positive anti-NMDA receptor antibodies have been tested, associated with clinical manifestations that suggest autoimmune encephalitis and a germ-cell tumour confirmed by pathology. Six patients have tested positive for anti-NMDA receptor antibodies associated with a germ-cell tumour and clinical manifestations of autoimmune encephalitis. Management includes aggressive immunosuppression and surgical removal.

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Antibody-associated CNS syndromes without signs of inflammation in the elderly

Neurology ◽

10.1212/wnl.0000000000004541 ◽

2017 ◽

Vol 89 (14) ◽

pp. 1471-1475 ◽

Cited By ~ 34

Author(s):

Domingo Escudero ◽

Mar Guasp ◽

Helena Ariño ◽

Carles Gaig ◽

Eugenia Martínez-Hernández ◽

...

Keyword(s):

Neurodegenerative Disorder ◽

Brain Mri ◽

Clinical Manifestations ◽

Memory Loss ◽

Autoimmune Encephalitis ◽

Surface Antigens ◽

Clinical Analysis ◽

Correct Identification ◽

Cognitive Deterioration ◽

Antibody Testing

Objective:To report the CNS syndromes of patients ≥60 years of age with antibodies against neuronal surface antigens but no evidence of brain MRI and CSF inflammatory changes.Methods:This was a retrospective clinical analysis of patients with antibodies against neuronal surface antigens who fulfilled 3 criteria: age ≥60 years, no inflammatory abnormalities in brain MRI, and no CSF pleocytosis. Antibodies were determined with reported techniques.Results:Among 155 patients ≥60 years of age with neurologic syndromes related to antibodies against neuronal surface antigens, 35 (22.6%) fulfilled the indicated criteria. The median age of these 35 patients was 68 years (range 60–88 years). Clinical manifestations included faciobrachial dystonic seizures (FBDS) in 11 of 35 (31.4%) patients, all with LGI1 antibodies; a combination of gait instability, brainstem dysfunction, and sleep disorder associated with IgLON5 antibodies in 10 (28.6%); acute confusion, memory loss, and behavioral changes suggesting autoimmune encephalitis (AE) in 9 (25.7%; 2 patients with AMPAR, 2 with NMDAR, 2 with GABAbR, 2 with LGI1, and 1 with CASPR2 antibodies); and rapidly progressive cognitive deterioration in 5 (14.3%; 3 patients with IgLON5 antibodies, 1 with chorea; 1 with DPPX antibody–associated cerebellar ataxia and arm rigidity; and 1 with CASPR2 antibodies).Conclusions:In patients ≥60 years of age, the correct identification of characteristic CNS syndromes (FBDS, anti-IgLON5 syndrome, AE) should prompt antibody testing even without evidence of inflammation in MRI and CSF studies. Up to 15% of the patients developed rapidly progressive cognitive deterioration, which further complicated the differential diagnosis with a neurodegenerative disorder.

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Anti-NMDA Receptor Encephalitis in a Patient with Previous Psychosis and Neurological Abnormalities: A Diagnostic Challenge

Case Reports in Psychiatry ◽

10.1155/2015/253891 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

R. David Heekin ◽

Maria C. Catalano ◽

Alfred T. Frontera ◽

Glenn Catalano

Keyword(s):

Nmda Receptor ◽

Psychiatric Symptoms ◽

Neuropsychiatric Symptoms ◽

Memory Loss ◽

Autoimmune Disorder ◽

Diagnostic Challenge ◽

Manic Symptoms ◽

Nmda Receptor Encephalitis ◽

Autonomic Instability ◽

Receptor Antibodies

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder characterized by IgG autoantibodies directed against the NR1 subunit of the NMDA glutamate receptor. Psychiatric symptoms are common and include psychosis, mania, depressed mood, aggression, and speech abnormalities. Neurological symptoms such as seizures, decreased responsiveness, dyskinesias, and other movement abnormalities and/or autonomic instability are frequently seen as well. We present the case of a woman who was followed up at our facility for over 14 years for the treatment of multiple neuropsychiatric symptoms. Initially, she presented with paresthesias, memory loss, and manic symptoms. Nine years later, she presented to our facility again, this time with left sided numbness, left eyelid droop, and word finding difficulties. Finally, five years later, she presented with manic symptoms, hallucinations, and memory impairment. During her hospitalization, she subsequently developed catatonic symptoms and seizures. During her stay, it was discovered that she was positive for anti-NMDA receptor antibodies and her symptoms responded well to appropriate therapy. This case demonstrates that it may be useful for clinicians to consider screening for anti-NMDA receptor antibodies in long-term patients with neuropsychiatric symptoms that have not adequately responded to therapy.

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Solitary juxtacortical lesion associated with anti-N-methyl-D-aspartate receptor encephalitis: a case report

BMC Neurology ◽

10.1186/s12883-020-01997-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Rupan Gao ◽

Xiang Zhang ◽

Abhijeet Kumar Bhekharee ◽

Yue Zhang

Keyword(s):

Nmda Receptor ◽

Frontal Lobe ◽

Brain Mri ◽

Brain Lesion ◽

Autoimmune Encephalitis ◽

Left Frontal Lobe ◽

Solitary Lesion ◽

Nmda Receptor Encephalitis ◽

Epileptiform Discharges ◽

Receptor Antibodies

Abstract Background Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a severe autoimmune encephalitis mediated by anti-NMDA receptor antibodies. Brain MRI manifestations vary and are non-specific. If there are any lesions, they tend to be diffusely or multifocally distributed. Solitary lesion is relatively rare. Case presentation We report a 16-year-old girl who initially presented with focal seizures but developed severe psychiatric and extrapyramidal symptoms later on. Brain MRI revealed a solitary juxtacortical demyelinating lesion in the left frontal lobe. No enhancement was noted. Electroencephalogram captured epileptiform discharges in the same region. NMDAR IgGs were tested positive in the serum and cerebrospinal fluid. Corticosteroid and intravenous IgG were administered and the patient completely recovered. Brain MRI revealed a fainter lesion in the left frontal lobe. Conclusion In very rare instances, anti-NMDA receptor encephalitis can present with a solitary brain lesion. A full panel of antibodies for autoimmune encephalitis is the key leading to the diagnosis.

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Autoimmune Limbic Encephalitis: When Psychiatric Symptoms Are Not What They Seem

10.26226/morressier.588f064fd462b8028d891808 ◽

2017 ◽

Author(s):

Ana Samico

Keyword(s):

Limbic Encephalitis ◽

Psychiatric Symptoms ◽

Autoimmune Limbic Encephalitis

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Autoimmune encephalitis in a South Asian population

BMC Neurology ◽

10.1186/s12883-021-02232-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Nilanka Wickramasinghe ◽

Dhanushka Dasanayake ◽

Neelika Malavige ◽

Rajiva de Silva ◽

Thashi Chang

Keyword(s):

Sri Lanka ◽

Psychiatric Symptoms ◽

South Asians ◽

Laboratory Data ◽

Clinical Manifestations ◽

Autoimmune Encephalitis ◽

Asian Population ◽

South Asian Population ◽

Clinical Presentations

Abstract Background Autoimmune encephalitis (AE) is now considered a main, potentially curable cause of encephalitis, but remains conspicuously underreported from South Asia. We studied the clinical characteristics in relation to their antibody status and outcomes of patients presenting with AE in Sri Lanka. Methods Patients admitting to government hospitals who were clinically suspected of AE by an on-site neurologist were prospectively recruited over a period of 12 months. Sera and cerebrospinal fluid were tested for NMDAR, AMPAR1, AMPAR2, LGI1, CASPR2, GABARB1/B2 antibodies (Ab) using commercial cell-based assays. Demographic, clinical and laboratory data were compiled into an investigator-administered proforma. Patients were reviewed at 1 year follow up either in person or via telephone. Results One-hundred and forty-two patients from 21 of 25 districts in Sri Lanka (median age = 20.5 years; range 1–86 years; females = 61.3%) were recruited. Of them, 65 (45.8%; median age = 19 years; range 1–86 years; females = 64.6%) fulfilled diagnostic criteria for probable NMDAR-antibody encephalitis (NMDARE) and 6 (4.2%; median age = 44 years; range 28–71 years; females = 83.3%) limbic encephalitis (LE). Abnormal behaviour (95.3%), seizures (81.5%) and movement disorders (69.2%) were the most frequent clinical manifestations of probable NMDARE. NMDAR-antibodies were detectable in 29 (44.6%) and not detectable in 36 in CSF of probable-NMDARE patients. Abnormal EEG was more frequent (p = 0.003) while a worse outcome (OR = 2.78; 95% CI = 0.88–9.09) and deaths (OR = 2.38; 95% CI = 0.67–8.33) were more likely in antibody-negative than antibody-positive probable-NMDARE. Most patients with LE had amnesia (50%) and/or confusion (100%) with agitation (83.3%) and seizures (100%) but none had detectable antibodies to any of the antigens tested. Conclusions NMDARE is the commonest type of AE among South Asians as is the case worldwide. Clinical presentations of NMDARAb-positive and NMDARAb-negative AE patients do not significantly differ but EEG may be a useful marker of an autoimmune basis for psychiatric symptoms.

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Enoxaparin-induced Wunderlich syndrome in a young patient with anti-GAD 65-associated opsoclonus and limbic encephalitis: a rare complication in a rare disease

BMJ Case Reports ◽

10.1136/bcr-2021-244916 ◽

2021 ◽

Vol 14 (10) ◽

pp. e244916

Author(s):

Saranya B Gomathy ◽

Animesh Das ◽

Awadh Kishor Pandit ◽

Achal Kumar Srivastava

Keyword(s):

Rare Disease ◽

Young Patient ◽

Clinical Condition ◽

Limbic Encephalitis ◽

Rare Complication ◽

Clinical Manifestations ◽

Autoimmune Encephalitis ◽

Rare Condition ◽

Gad 65 ◽

Good Improvement

Wunderlich syndrome is a rare condition characterised by acute spontaneous non-traumatic renal haemorrhage into the subcapsular and perirenal spaces. Our case of anti-GAD65-associated autoimmune encephalitis (AE), aged 30 years, developed this complication following use of enoxaparin and was managed by selective glue embolisation of subsegmental branches of right renal cortical arteries. Our case had opsoclonus as one of the clinical manifestations, which has till now been described in only two patients of this AE. This patient received all forms of induction therapies (steroids, plasmapheresis, intravenous immunoglobulin and rituximab) following which she had good improvement in her clinical condition. The good response to immunotherapy is also a point of discussion as this has been rarely associated with anti-GAD65 AE.

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Frequency and temporal sequence of clinical features in adults with anti-NMDA receptor encephalitis presenting with psychiatric symptoms

Psychological Medicine ◽

10.1017/s0033291718003665 ◽

2018 ◽

Vol 49 (16) ◽

pp. 2709-2716 ◽

Cited By ~ 3

Author(s):

Ronald J. Gurrera

Keyword(s):

Nmda Receptor ◽

Clinical Features ◽

Psychiatric Symptoms ◽

Autoimmune Encephalitis ◽

Signs And Symptoms ◽

Nmda Receptor Encephalitis ◽

Nmdar Encephalitis ◽

Unexplained Fever ◽

Study Inclusion

AbstractBackgroundAnti-NMDA receptor (NMDAr) encephalitis is the most common autoimmune encephalitis in adults. It mimics psychiatric disorders so often that most patients are initially referred to a psychiatrist, and many are misdiagnosed. Without prompt and effective treatment, patients are likely to suffer a protracted course with significant residual disability, or death. This study focuses on the frequency and chronology of salient clinical features in adults with anti-NMDAr encephalitis who are likely to be first evaluated by a psychiatrist because their presentation suggests a primary psychiatric disorder.MethodsA systematic search of PubMed and EMBASE databases identified published reports of anti-NMDAr encephalitis associated with prominent behavioral or psychiatric symptoms. After eliminating redundancies, the frequencies and relative timing of clinical features were tabulated. Signs and symptoms were assigned temporal ranks based on the timing of their first appearance relative to the first appearance of other signs and symptoms in each patient; median ranks were used to compare temporal sequencing of both individual features and major symptom domains.ResultsTwo hundred thirty unique cases (185 female) met study inclusion criteria. The most common features were seizures (60.4%), disorientation/confusion (42.6%), orofacial dyskinesias (39.1%), and mutism/staring (37.4%). Seizures, fever, and cognitive dysfunction were often the earliest features to emerge, but psychiatric features predominated and sequencing varied greatly between individuals.ConclusionsClinicians should consider anti-NMDAr encephalitis when new psychiatric symptoms are accompanied by a recent viral prodrome, seizures or unexplained fever, or when the quality of the psychiatric symptoms is unusual (e.g. non-verbal auditory hallucinations).

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Neurobrucellosis mimicking primary vasculitis of the central nervous system: we should perform a metagenomic analysis of the cerebrospinal fluid prior to brain biopsy

10.5327/1516-3180.422 ◽

2021 ◽

Author(s):

Marina Barrionuevo Mathias ◽

Fernando Gatti ◽

Gustavo Bruniera ◽

Vitor Paes ◽

Gisele Sampaio Silva ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Psychiatric Symptoms ◽

Brain Mri ◽

Genetic Material ◽

Clinical Manifestations ◽

Brain Biopsy ◽

Metagenomic Analysis ◽

Normal Brain ◽

The Central Nervous System

Context Primary angiitis of the central nervous system (PACNS) is characterized by the inflammation of small and medium CNS arteries; the clinical manifestations include headache, cognitive impairment and focal neurological deficits. The gold standard test for diagnosis is brain biopsy. Neurobrucellosis is an infection associated with cattle farming, which leads to neurological and psychiatric symptoms. We report a case of neurobrucellosis mimicking PACNS. Case report Male, 32 years old, with fever, headache, dizziness and cognitive impairments for 30 days. History of stroke 2 years before, with mild sequelae right hemiparesis; investigation showed suspected intracranial dissection. On physical examination, he had apathy, preserved strength, reduced reflexes with plantar flexor responses. General laboratory tests, autoantibodies and serology were normal. Brain MRI showed deep left nucleocapsular gliosis and cerebral angiography revealed stenosis of the ICA and MCA. CSF showed 42 cells/ mm³, glucose 46 mg/dL, protein 82 mg/dL. Blood PCR was negative for Brucella. Immunophenotyping of the CSF and PET-CT excluded neoplasia. Brain biopsy was inconclusive for vasculitis. Metagenomic analysis of the CSF detected 78% of Brucella genetic material. Serum agglutination test was 1:40 for brucella. Conclusions PACNS is diagnosed by exclusion. The patient filled criteria for possible PACNS, image compatible with vascular stenosis, but inconclusive brain biopsy. Brucellosis is an endemic disease in underdeveloped countries that can present as CNS vasculitis. Metagenomic analysis allows the detection of different pathogens using a single method. The case illustrates the use of metagenomics in rare diseases characterized by vasculitis, with change in clinical outcomes and conduct.

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