Extreme Delta Brush Pattern Research Articles

Persistent psychosis associated with extreme delta brush in anti-NMDA receptor encephalitis: a case report

BackgroundAnti-NMDAR encephalitis is an emerging differential diagnosis of first episode and persistent psychosis in the psychiatric community, as clinical manifestations include psychiatric symptoms, cognitive dysfunction, seizures, decreased consciousness, and dyskinesias. This disease is associated with extreme delta brush (EDB), but the significance and temporal course of this EEG pattern still needs to be determined. Herein, we report a case of anti-NMDAR encephalitis with persistent psychosis associated with EDB occurrence on multiple occasions during a 5-year disease course.Case presentationA 15-year-old girl was diagnosed with anti-NMDAR encephalitis and treated with progressive improvement. Four years after initial manifestations, an EDB pattern was seen on electroencephalogram (EEG) without new neurological symptoms. She had residual symptoms of episodic auditory hallucinations and impulsivity. One year later, the patient had a recurrence of neurological symptoms (seizures, dyskinesias and impaired attention), persisting with EDB on EEG. Clinical symptoms and EDB resolved after second-line treatment with rituximab.ConclusionWe describe the first case of persistent psychosis in anti-NMDAR encephalitis associated with extreme delta brush on multiple EEGs on prolonged follow-up. Electroencephalographic patterns such as EDB may serve as markers of residual disease activity, including psychiatric symptoms. Further studies with prolonged EEG monitoring are needed to better understand these findings.

КЛИНИЧЕСКИЕ ПРОЯВЛЕНИЯ АНТИ-NMDA-РЕЦЕПТОРНОГО ЭНЦЕФАЛИТА У ДЕТЕЙ

The aim of the study was to determine the clinical features of anti-NMDAR encephalitis in children. Materials and methods of research: 11 patients were selected from the group of children with autoimmune encephalitis, who met the diagnostic criteria for reliable anti-NMDAR encephalitis. A retro-prospective analysis of clinical symptoms, laboratory, neurophysiological and neuroimaging data, treatment, duration of primary hospitalization and long-term results of treatment was carried out, neuropsychological testing of patients was performed in the follow-up. Results: the age of the patients was 8.5±4.4 years, the gender composition of boys/girls was 1/10 (9.1%/90.9%). The average follow-up period was 17±12 months. In 73% of cases, there was an acute onset of the disease without a prodromal phase and with rapidly growing signs of neurological dysfunction: behavior change (11/100%), epileptic seizures (11/100%), speech impairment (10/90.9%), movement disorders (10/90.9%), disturbed sleep/wakefulness rhythm (9/81.8%), hallucinations (5/45.5%), autonomic disorders (6/54.5%), sensory disturbance (1/9,1%). In 82% of cases, therapy was required in the intensive care unit. When analyzing EEG monitoring in children, the extreme delta brush pattern was revealed in only one patient. Neuroimaging revealed no specific changes in the substance of the brain. The paraneoplastic nature of the disease could not be established in any case. 4 patients (36.36%) had relapses of the disease after 1.5–27 months. from the onset of the disease. All children showed a favorable outcome without a gross neurological deficit, but complaints of increased fatigue, headaches, poor memory, a decrease in vocabulary, and impulsive behavior persisted.

Understanding Seizures and Prognosis of the Extreme Delta Brush Pattern in Anti-N-Methyl-D-Aspartate (NMDA) Receptor Encephalitis: A Systematic Review.

Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (ANMDARE) is an autoimmune disorder with neurological and psychiatric features. The disease presents with a viral prodrome, followed by psychiatric manifestations. In the next phase, movement disorders or/and seizures occur. Finally, in the last phase, there is a decrease in the level of consciousness. Central hypoventilation and autonomic dysfunction can occur. Recently a unique EEG (electroencephalogram) pattern has been associated with anti-NMDA receptor encephalitis, the extreme delta brush (EDB). Although the association of the EDB with ANMDARE is known by the medical community, its significance is mainly unknown. A systematic review on NMDARE is also scarce. We decided to conduct a systematic review on this topic to consolidate the knowledge and establish the importance of the EDB as a prognostic factor. To conduct this systematic review, we used only studies conducted in humans, written in English, and published in the last 20 years. We used PubMed as a database and searched the following search terms: ("NMDA encephalitis"[Title/] AND "Epilepsy"[Title/]) OR (NMDA encephalitis"[Title/] AND "seizures" [Title/]) OR ("NMDA encephalitis"[Title/] AND "extreme delta brush"[Title/]). The protocol used for this systematic review was the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) protocol, and to analyze the bias of the studies, we used the ROBINS-1 tool.Eight studies were collected from our search strategy. Our data pulling showed that seizures were present in 178/249 (71.48%) patients. Status Epilepticus was reported in 29/96 (30.20%), and the EBD was seen in 30.89% (55/178) patients with seizures. The range of EDB was 5.9%-33% among the studies. Because the sample size was small, the statistical power was decreased. We had a low overall risk of bias. The wide range in the results could be related to the timing of the EEG recording. EDB was associated overall with increased length of hospital stay, increased ICU admission, and incidence of status epilepticus. The etiology of the EDB remains mainly unknown. However, it has been postulated that in NMDAR encephalitis, there is a disruption of the rhythmic neuronal activity. When antibodies block/target the NMDAR, the rhythmic neuronal activity is disrupted, leading to the unique EDB pattern. Another theory suggests that delta activity is caused because of focal abnormalities in the brain, and the superimposition of the beta waves is related to the alterations of the NMDA receptors.

Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis

Overall, immunotherapy has been shown to improve outcomes and reduce relapses in individuals with N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis (NMDARE); however, the superiority of specific treatments and combinations remains unclear. To map the use and safety of immunotherapies in individuals with NMDARE, identify early predictors of poor functional outcome and relapse, evaluate changes in immunotherapy use and disease outcome over the 14 years since first reports of NMDARE, and assess the Anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score. Systematic search in PubMed from inception to January 1, 2019. Published articles including patients with NMDARE with positive NMDAR antibodies and available individual immunotherapy data. Individual patient data on immunotherapies, clinical characteristics at presentation, disease course, and final functional outcome (modified Rankin Scale [mRS] score) were entered into multivariable logistic regression models. The planned study outcomes were functional outcome at 12 months from disease onset (good, mRS score of 0 to 2; poor, mRS score greater than 2) and monophasic course (absence of relapse at 24 months or later from onset). Data from 1550 patients from 652 articles were evaluated. Of these, 1105 of 1508 (73.3%) were female and 707 of 1526 (46.3%) were 18 years or younger at disease onset. Factors at first event that were significantly associated with good functional outcome included adolescent age and first-line treatment with therapeutic apheresis, corticosteroids plus intravenous immunoglobulin (IVIG), or corticosteroids plus IVIG plus therapeutic apheresis. Factors significantly associated with poor functional outcome were age younger than 2 years or age of 65 years or older at onset, intensive care unit admission, extreme delta brush pattern on electroencephalography, lack of immunotherapy within the first 30 days of onset, and maintenance IVIG use for 6 months or more. Factors significantly associated with nonrelapsing disease were rituximab use or maintenance IVIG use for 6 months or more. Adolescent age at onset was significantly associated with relapsing disease. Rituximab use increased from 13.5% (52 of 384; 2007 to 2013) to 28.3% (311 of 1100; 2013 to 2019) (P < .001), concurrent with a falling relapse rate over the same period (22% [12 of 55] in 2008 and earlier; 10.9% [35 of 322] in 2017 and later; P = .006). Modified NEOS score (including 4 of 5 original NEOS items) was associated with probability of poor functional status at 1 year (20.1% [40 of 199] for a score of 0 to 1 points; 43.8% [77 of 176] for a score of 3 to 4 points; P = .05). Factors influencing functional outcomes and relapse are different and need to be considered independently in development of evidence-based optimal management guidelines of patients with NMDARE.

Anti-N-methyl-d-aspartate Receptor Encephalitis Related Sinus Node Dysfunction and the Lock-Step Phenomenon.

Described in 2007, anti-N-methyl-d-aspartate receptor encephalitis (ANMDARE) is a rare autoimmune limbic encephalitis affecting young adults (predominantly women of reproductive age) and is a paraneoplastic manifestation of ovarian teratoma in about half of the cases. ANMDARE is characterized by psychiatric changes, neurological changes, autonomic instability and cardiac dysrhythmias. In this report, we present a 36-year-old woman who was 16 weeks pregnant and brought to the hospital with confusion and subsequently had a seizure with Electroencephalography (EEG) demonstrated an extreme delta brush pattern consistent with ANMDARE. Patient developed sinus nodal dysfunction and was also found to have ovarian teratoma, a rather typical presentation for ANMDARE, that is considered a paraneoplastic syndrome for ovarian teratoma. In this report, we highlight the cardiac manifestation of ANMDARE, the pathophysiology associated with autonomic instability, and management strategies of this rare, and largely devastating illness.

Characterization and Outcomes of Epileptic Seizures in Mexican Pediatric Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

IntroductionAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most common autoimmune encephalitides. The frequency of anti-NMDAR encephalitis is known to exceed the frequency of any individual viral encephalitis in young subjects. Epileptic seizures are a cardinal symptom in anti-NMDAR encephalitis; a significant amount of pediatric patients exhibit seizures as the first symptom of the disease, and most of them will develop them during the acute phase. The use of antiepileptic drugs (AEDs) is a cornerstone of the treatment of these patients, but the choice of agent and duration of treatment is currently unknown.Materials and methodsThis was a single-center retrospective review case series of all pediatric patients with a confirmed diagnosis of anti-NMDAR encephalitis and epileptic seizures admitted to the National Institute of Pediatrics in Mexico City from January 2012 to July 2019.ResultsWe included a total of 31 patients (males 64.5%, median age: 10 years). No patient showed evidence of teratoma; only 38% of cases had a viral prodrome. Most patients initially exhibited psychiatric symptoms (51%), but the leading cause in soliciting medical assistance was the presence of epileptic seizures (71%). About 85% of patients presented epileptic seizures during the course of the illness, predominantly focal onset seizures (42% focal to bilateral tonic-clonic seizures, 32% focal seizures with impaired awareness). Electroencephalogram (EEG) was abnormal in 97% of patients; the characteristic extreme delta brush pattern was found in 9% of patients. Two AEDs on average were required to control seizures during the acute stage. In six (19%) patients, human herpesvirus (HHV) was detected in cerebrospinal fluid (CSF); all of them had epileptic seizures, which were more resistant to pharmacological treatment during the acute phase, requiring a higher number of AED (median 2.5 vs. 2). The development of epilepsy after acute encephalitis was uncommon; at 24 months, only one patient continued to have epileptic seizures. One of the factors most closely related to the persistence of epileptic seizures was the inadequate response to immunotherapy after four weeks. The functional prognosis was generally good; at a two-year follow-up, only two (10%) patients had a significant disability [modified Rankin Scale (mRS) score: 3-5]; both patients had seizures at a one-year follow-up.ConclusionsSustained use of AEDs after the acute phase of anti-NMDAR encephalitis is controversial. We found that the continuation of AEDs after the acute phase could be considered in the following scenarios: status epilepticus (SE), inadequate response to immunotherapy at four weeks, and a high mRS score at discharge and during follow-up. In other cases, discontinuation of AED may be warranted. More studies are needed in our country to replicate these results.

Effects of Rapid Eye Movement Sleep in Anti-NMDAR Encephalitis With Extreme Delta Brush Pattern

Effects of Rapid Eye Movement Sleep in Anti-NMDAR Encephalitis With Extreme Delta Brush Pattern

P.080 Effects of REM sleep in anti-NMDA receptor encephalitis with extreme delta brush pattern

Background: Seizures are rare in REM sleep. To our knowledge, the effects of different sleep stages in anti-NMDA encephalitis have not been studied. Methods: Case report. Results: 32 year-old healthy female presented with acute fluctuating level of consciousness with episodic impulsivity, disorientation, and emotional outbursts following 3 days of headache. Her temperature was 37.8°C and she was started on ceftriaxone, vancomycin, and acyclovir. CSF only showed a total nuclear cell count of 182 and pleocytosis. MRI revealed increased T2 hyperintense right lateral temporal and parietal cortical thickening. EEG revealed right frontotemporal seizures with left sided rhythmic jerking, and an extreme delta brush pattern. Interestingly, seizures and extreme delta brush disappeared in REM sleep. After HSV PCR was negative, she was immunosuppressed with corticosteroids, IVIG, rituximab, and cyclophosphamide, given the extreme delta brush pattern. Repeat CSF analysis eventually yielded highly positive anti-NMDA antibodies. Ten weeks later, she became seizure free. Conclusions: For the first time, we report REM sleep in a case of anti-NMDA encephalitis during which there was absence of extreme delta brush and ictal EEG patterns. This observation may provide insight into the ongoing debate over whether extreme delta brush is an ictal EEG pattern.

Confusional state in a pregnant woman: A case of NMDA receptor encephalitis during pregnancy

We report the case of a pregnant female presenting with behavioral change and hallucinations followed by focal seizures with impaired awareness. EEG revealed generalized slowing interspersed with extreme delta-brush pattern and MRI brain was normal. Both Serum and CSF anti-N-methyl-d-aspartate receptor (NMDAR) antibodies were positive. Patient had a prolonged hospital stay with full recovery and delivered a healthy baby, highlighting the significance of early diagnosis and management in this disorder.

EEG Findings May Serve as a Potential Biomarker for Anti-NMDA Receptor Encephalitis.

Objective To determine if an electroencephalographic (EEG) characteristic, beta:delta power ratio (BDPR), is significantly higher for N-methyl-d-aspartate receptor encephalitis (NMDARE) patients than for non-NMDARE patients on presenting EEG. Identification of an additional EEG biomarker with significant specificity for NMDARE (in the absence of frank delta brush) could potentially allow for early identification of at-risk patients. Methods Single center retrospective comparison of NMDARE and non-NMDARE consecutive cases of encephalitis, collated over a 6-year period (from 2008 to 2014). Results None of the 10 NMDARE patients displayed the extreme delta brush pattern on EEG previously described, but the ratio of BDPR was significantly higher for NMDARE patients (P < .005). There was no significant relationship between BDPR and the time of recording from symptom onset. Additional analysis of clinical characteristics also indicated that the patients with NMDARE (median age 19.5 years) were younger than the 5 patients with non-NMDARE (median age 36 years). Encephalopathy, seizure, and psychiatric complaints were the most common diagnoses at time of first health care presentation and did not favor a single etiology, though the latter was present only in the NMDARE population (50% at T0). Prodromal illness featuring headache was more common in the non-NMDARE population. Outcomes, as measured by the Modified Rankin Scale, were globally better in the NMDARE group. Conclusions Patients with NMDARE had a significantly higher BDPR on EEG when compared with non-NMDARE patients even in the absence of extreme delta brush. This suggests that early EEG characteristics may be helpful in distinguishing NMDARE from non-NMDARE.

Extreme delta brush guides to the diagnosis of anti-NMDAR encephalitis

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a treatable but often misdiagnosed autoimmune encephalitis. Diagnosis depends on NMDAR antibody testing, which may not be readily available. Alternatively, the electroencephalogram (EEG) extreme delta brush pattern may provide a valuable immediate indicator for the diagnosis of anti-NMDAR encephalitis. A 32-year-old female (case 1) presented with fever, headache, behavioral changes, confusion, intractable seizures, central hypoventilation, dysautonomia, facial and limb dyskinesias, and comorbid ovarian teratoma. Cerebral spinal fluid (CSF) testing revealed mild lymphocytic pleocytosis while brain MRI results were normal. A 45-year-old male (case 2) presented with major behavioral changes and rare seizures. Results of routine CSF testing and brain MRI scanning were unremarkable. In both cases, EEG initially revealed the extreme delta brush (EDB) pattern of beta bursting on the peaks and/or the troughs of delta waves, which led to subsequent NMDAR antibody testing and the confirmative diagnosis. Thus, EDB may be a readily accessible sign for suspected anti-NMDAR encephalitis.

Extreme delta brush

To determine continuous EEG (cEEG) patterns that may be unique to anti-NMDA receptor (NMDAR) encephalitis in a series of adult patients with this disorder. We evaluated the clinical and EEG data of 23 hospitalized adult patients with anti-NMDAR encephalitis who underwent cEEG monitoring between January 2005 and February 2011 at 2 large academic medical centers. Twenty-three patients with anti-NMDAR encephalitis underwent a median of 7 (range 1-123) days of cEEG monitoring. The median length of hospitalization was 44 (range 2-200) days. Personality or behavioral changes (100%), movement disorders (82.6%), and seizures (78.3%) were the most common symptoms. Seven of 23 patients (30.4%) had a unique electrographic pattern, which we named "extreme delta brush" because of its resemblance to waveforms seen in premature infants. The presence of extreme delta brush was associated with a more prolonged hospitalization (mean 128.3 ± 47.5 vs 43.2 ± 39.0 days, p = 0.008) and increased days of cEEG monitoring (mean 27.6 ± 42.3 vs 6.2 ± 5.6 days, p = 0.012). The modified Rankin Scale score showed a trend toward worse scores in patients with the extreme delta brush pattern (mean 4.0 ± 0.8 vs 3.1 ± 1.1, p = 0.089). Extreme delta brush is a novel EEG finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness. Although the specificity of this pattern is unclear, its presence should raise consideration of this syndrome.