Delta brush on EEG: a characteristic EEG finding in autoimmune encephalitis
- 1 Neurology, The Aga Khan University Hospital, Main Campus Karachi, Karachi, Sindh, Pakistan
- 2 Neurophysiology, The Aga Khan University Hospital, Main Campus Karachi, Karachi, Sindh, Pakistan
- Correspondence to Dr Shafaq Saleem; drshafaqsaleem@gmail.com
Abstract
A woman in her late 20s was admitted via the emergency department in the psychiatric ward with acute-onset behavioural changes and suicidal thoughts in the past 2 weeks. Workup revealed positive N-methyl-D-aspartate (NMDA) receptor antibodies in cerebrospinal fluid and electroencephalogram (EEG) showing a specific pattern of delta brush on bilateral frontal regions. Other investigations were unremarkable. The patient was started on intravenous methylprednisolone 1000 mg for 5 days with oral steroids. She responded on steroids. She has been recommended for workup for teratoma/mediastinal tumours with NMDA receptor encephalitis is an autoimmune disorder predominantly affecting women of childbearing age. Delta brush pattern on EEG is specific for NMDA receptor encephalitis hence can be used as a diagnostic tool. It is advisable to investigate any patient with the presentation of mental deterioration for pathological causes. However, treatment with immunotherapy increases the chance of survival and may prevent cognitive impairment.
Background
N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder that predominantly affects young women. It poses a challenge to neurologists and psychiatrists presenting with acute psychiatric symptoms, seizures and encephalopathy. Diagnosis of this treatable encephalitis depends on positive cerebrospinal fluid (CSF) NMDA receptor antibodies. Electrographical delta brush pattern in adults is a useful diagnostic investigation that is also a prognostic indicator.
Case presentation
A woman in her 20s, with no psychiatric history, was primigravida with a gestational age of 6 weeks when brought to the emergency department with acute-onset confusion, restlessness and erratic behaviour. Prior to the presentation, she also attempted suicide at home. Symptoms progressively increased over the days, so she was finding it difficult to do her daily tasks like calculations and signing forms. On admission, the patient was agitated and restless. The examination was unremarkable except for the irrelevant talk and inability to follow complex commands. Due to acute psychosis, she was admitted to the psychiatry department. MRI of the brain including T1-weighted, T2-weighted, diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) was negative for abnormal signals or enhancement. CSF examination showed lymphocytic pleocytosis (white cell count 12 x 109/L with 100% lymphocytes), proteins 55 mg/dL and glucose 55 mg/dL (random blood glucose 177 mg/dL). CSF culture was negative. Laboratory investigations including complete blood count, renal function tests, liver function tests and thyroid profile were negative for any abnormality. Ultrasound of the pelvis was negative for any abnormality. The serum antinuclear antibodies profile showed insignificant positivity for anti-Ro. A 30-minute recording of an electroencephalogram (EEG) showed a bifrontal delta brush pattern superimposed on delta troughs and peaks suggesting NMDA encephalitis (figure 1). Later, fluorescein staining of CSF revealed NMDA receptor antibody-positive titres (+++) (figure 2). She was transferred under neurology services and was started on a 5-day course of intravenous 1000 mg methylprednisolone. The patient showed improvement after five doses of methylprednisolone. After 5 days of inpatient stay, she was discharged home on oral prednisolone 60 mg/day in tapering doses of 10 mg/week for 6 weeks. A discharge examination showed improvement in her agitation and confusional state.
Bilateral longitudinal montage of a standardised 30-minute electroencephalogram showing bihemispheric cortical dysfunction most prominent in bilateral frontal region. Superimposed faster activity on delta waves predominantly over bilateral frontal region noted (extreme delta brush pattern), which is suggestive of an N-methyl-D-aspartate receptor encephalitis.
Immunostaining with fluorescein-labelled green dye of cerebrospinal fluid showing green-coloured antigen-antibody complex in dark background of non-reactive cells showing positive N-methyl-D-aspartate receptor antibodies.
Treatment
She was started on a 5-day course of intravenous 1000 mg methylprednisolone. The patient showed improvement after five doses of methylprednisolone. After 5 days of inpatient stay, she was discharged home on oral prednisolone 60 mg/day in tapering doses of 10 mg/week for a period of a total of 6 weeks.
Outcome and follow-up
She showed improvement in her agitation and confusional state after five doses of methylprednisolone. On the outpatient follow-up visit, she talked about resuming her work and was back to her previously pre-diseased condition. She has been recommended further imaging to exclude the possibility of teratoma/mediastinal tumours in consideration of the association with the disease. A repeat EEG was not performed.
Discussion
NMDA receptor encephalitis, a common cause of non-viral encephalitis, manifests as a psychological and cognitive decline in women of childbearing age.1 Pathogenesis reveals antibodies are expressed in the prefrontal nerve cell membrane and the hippocampus leading to the term ‘limbic encephalitis’. The disorder is rare in pregnancy and the postpartum period. It is associated with paraneoplastic ovarian teratomas, small cell lung carcinomas, neuroblastomas and mediastinal tumours.2
The disorder can occur at any time during pregnancy. Recurrences in pregnancy may also occur. It has a variable clinical course and prognosis in pregnancy. Xiao et al reported a case of a woman in her 20s who was in 28 weeks of gestation, and delivered a healthy baby after responding to treatment on steroids and plasmapheresis.2 Joubert et al, in a case series, reported no cognitive decline or neurological deficit in infants born to NMDA receptor-positive mothers. A retrospective analysis of 13 patients with NMDA receptor encephalitis in pregnancy was analysed; the majority of cases occurred in the first trimester followed by second trimester occurrences.3
However, the disease is treatable, with most patients recovering without any neurological disability. Most of the patients respond to first-line immunotherapy with steroids/immunoglobulins and plasmapheresis.4 Those not responding to first-line therapy showed better outcomes with second-line therapy, which includes rituximab and cyclophosphamide. It is observed that those given treatments with first-line immunotherapy do better than those without. Second-line therapy has been effective in refractory cases with a good prognosis among receivers,4–7 as illustrated in the algorithm by SS (figure 3). Research has given us some insight into the pathogenesis and treatment during pregnancy but still, the disease course and outcome need to be further explored. Limbic encephalitis in pregnancy follows a variable course during pregnancy.8
Treatment algorithm for NMDA encephalitis by Shafaq Saleem. IV, intravenous; NMDA, N-methyl-D-aspartate.
Diagnosis of the disease is based on extensive workup excluding all other causes of encephalitis. Lumbar puncture results show non-specific lymphocytic pleocytosis and increased proteins as we also observed in our patient, but CSF results showing positive NMDA receptor antibodies are diagnostic. Literature search has revealed non-specific MRI of the brain features varying from T2 and FLAIR hyperintensities with occasional findings of subtle enhancement in areas involving both cerebral cortices and brainstem, but medial temporal lobes are frequently affected.9
Electrodiagnostic testing in patients with NMDA receptor encephalitis shows broad EEG features correlating with disease features of encephalitis. EEG of diagnosed patients is most of the time abnormal, showing non-specific slowing in the theta and delta range. However, some patients present with clinical and electrographical seizures. A systematic review by Gillinder et al showed encephalopathic changes along with other findings like generalised rhythmic delta activity, extreme delta brush (EDB), sharp waves, periodical lateralised discharges and status epilepticus.10–12
EDB on EEG, though not being the most frequent finding in patients with NMDA receptor encephalitis, is highly specific for the diagnosis with a prevalence of 30% in patients.12–15 However, the results of an observational study showed detection in 42.9% of the patients.16 It is considered to be the electrographical marker of NMDA receptor encephalitis, characterised by delta activity with a frequency of 1–3 Hz superimposed with a brush pattern of a rhythmic burst of 20–30 Hz.13 It is so named due to the symmetrical pattern normally observed in premature infants where it can arise in any region of the brain. Pathogenesis though is still unclear, but a hypothesis postulates that blocking NMDA receptors by antibodies leads to interference in rhythmic pattern, giving rise to EDB. EDB is a normal EEG finding in premature infants and persists up to neonatal age. Nevertheless, it may predict forthcoming seizures.14 Despite being the sensitive marker to guide towards NMDA encephalitis diagnosis, EDB pattern can rarely be seen with other diagnostic aetiologies like hypoxic brain injury, brain tumour, stroke and mesial temporal lobe epilepsy.17
EDB on EEG in observational studies has usually revealed resistance in response to first-line immunotherapy and the need for aggressive escalation to other therapeutic measures,18 unlike in our patient. This unique pattern shows improvement with treatment in patients whose repeat EEG was done. Patients with EDB follow a more severe clinical course,19 which has been associated with prolonged hospital admission and a poorer outcome.10 16 20
Therefore, the delta brush pattern can aid in diagnosing NMDA encephalitis. It has diagnostic and treatment implications leading to a favourable outcome if treated early.
Learning points
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This case highlights the unique electroencephalogram (EEG) feature of extreme delta brush occasionally seen in patients with N-methyl-D-aspartate (NMDA) receptor encephalitis.
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Neuropsychiatric manifestations can be a presentation of many neurological diseases with or without pregnancy, but NMDA receptor encephalitis is rare with the possibility of a specific pattern of extreme delta brush on electrodiagnostic testing.
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Therefore, electrographical findings of EEG can be used as a diagnostic tool in patients with NMDA receptor encephalitis, as well as an aid in prognostication of patients in certain cases.
Ethics statements
Patient consent for publication
Footnotes
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Twitter @FaizanAbdulla11
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Contributors Supervised by SJS. The patient was admitted under SJS. This case report was written, drafted and edited by SS. FAQ and DK contributed to article writing. Critical analysis was done by DK. EEG contribution was done by FAQ.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.
References
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