2017-18Research/Prognosis/PR

The NEOS score reliably predicted poor clinical outcome (mRS ≥3) in children in the first year after diagnosis (p = 0.0014) and beyond (p = 0.036, 16 months after diagnosis). A score adapted to the pediatric cohort by adjusting the cutoffs of the 5 NEOS components did not improve predictive power. In addition to these 5 variables, further patient characteristics such as the “Herpes simplex virus encephalitis (HSE) status” and “age at disease onset” influenced predictability and could potentially be useful to define risk groups. NEOS also predicted cognitive outcome with higher scores associated with deficits of executive function (p = 0.048) and memory (p = 0.043).

Conclusion: CASE score can be used for monitoring the severity of pediatric AE patients. It also has prognostic usefulness for predicting functional independence on follow-up.

103 pediatric AE patients participated in the study. AE is a treatable disease that can occur in children of all ages. The mortality rate is low, as most patients have a good response to immune therapy. Compared with the older children, infants and young children (≤ 3 years old) with anti-NMDAR encephalitis have a higher incidence of fever and status epilepticus, more severe condition, higher PICU admission rate and worse prognosis. AE patients with high maximum mRS scores and PICU admissions may require second-line immunotherapy.

CONCLUSION: There is a close correlation between modified Rankin Scale (mRS) scores and the immune function index CD4/CD8 in children with autoimmune encephalitis (AE) when they are admitted to the hospital. A young age, disturbance of consciousness, limb dyskinesia, abnormal immune function in remission and anti-NMDAR encephalitis are risk factors for poor prognoses in children with autoimmune encephalitis (AE). Clinical treatment requires more attention.

Antibody-negative but possible AE is frequent in children who may have a more severe neurological impairment and higher NLR than antibody-positive AE. Aggressive immunotherapy in antibody-negative AE is essential to achieve a good prognosis.

This retrospective study analyzed the clinical characteristics of autoimmune encephalitis (AE) patients to explore the predictors of poor prognosis. According to the modified Rankin scale score at the last follow-up, the functional prognosis of the patients was reflected. And the prognosis of the patients was comprehensively evaluated by the functional prognosis and the relapse of the patients. The results showed that disturbance of consciousness and delayed first-line immunotherapy were independent risk factors for the poor functional prognosis of AE. In addition, patients with psychiatric symptoms, should be alert for relapse.

 Cognitive impairment, fatigue, and sleep disturbances affect most recovering AME patients. This realization highlights the need for outcome measures that encompass more than motor function. 

Summary: Good outcomes continue to be reported in recovering patients, emphasizing the high potential for recovery following antibody-mediated encephalitis(AME). However, cognitive, behavioral, and physical sequelae may limit the potential for great outcomes following AME. Multidisciplinary follow-up is needed to recognize and treat sequelae that compromise long-term recovery and limit quality of life in recovering patients.

In this institutional cohort study, patients diagnosed with seronegative AE with available 2-year outcomes were analysed for the disease course, 2-year outcome prediction system, effect of immunotherapy, necessity of further immunotherapy at 6 or 12 months, and pattern of brain atrophy. Seronegative AE was subcategorized into antibody-negative probable AE (ANPRA), autoimmune limbic encephalitis (LE), and acute disseminated encephalomyelitis (ADEM). Poor 2-year outcome was defined by modified Rankin scale [mRS] scores 3‒6, and the 2-year serial data of Clinical Assessment Scales in Autoimmune Encephalitis (CASE) score was used for longitudinal data analyses. A total of 147 patients were included. The frequency of achieving a good 2-year outcome (mRS 0‒2) was 56.5%. The ANPRA subtype exhibited the poorest outcomes, although the baseline severity was similar among the subtypes.

In patients with persistent disease at 6 months, continuing immunotherapy was associated with more improvement, while the effect of continuing immunotherapy for more than 12 months was unclear. In the longitudinal analysis of MRI, the development of cerebellar atrophy indicated poor outcomes, while the absence of diffuse cerebral atrophy or medial temporal atrophy indicated the possibility of a good outcome.

Conclusions: (1) Elderly patients with anti-GABA_BR antibodies, especially those with severe symptoms, serum tumor markers, and additional onconeuronal antibodies, should be screened for lung cancer. (2) Anti-GABA_BR encephalitis with tumors has a poor prognosis. (3) Most patients without tumors achieve self-care, but some still experience remaining neurological deficits.

Ab-negative AE was associated with poorer cognitive outcomes than NMDARE at 1-year follow-up. Further studies are required to evaluate if immunotherapy can be optimized to improve outcome.

The primary goals of the study were: (1) to develop early predictive model which distinguished poor from good prognosis of patients with AE using a nomogram; and (2) to evaluate nomogram performance using patient-level independent data.  173 subjects were included in the final analysis. 

In this study, we identified age, viral prodrome, consciousness impairment, memory dysfunction and autonomic dysfunction for predicting poor prognosis of AE at discharge using a multivariable regression model. We found that elderly patients were more likely to have poor prognosis than younger individuals. The nomogram, deriving from the model, could accurately predict prognosis in patients with AE graphically and provided a personalized outlook. Our study creates a novel model to pick up patients who probably receive poor prognosis and allows physicians to provide a tailored clinical therapeutic regimen for each patient. Precision medicine for AE patients would lead to favorable prognosis and save their medical cost.

This article explains different antibodies and the course of recovery that is currently understood.

Each neuronal antibody exerts a distinct mechanistic effect and while the downstream effects all include cognitive dysfunction, the affected domains vary between subtypes. However, there is much work to be done in fully
characterizing both the acute and chronic impairments of the  encephalitic syndromes; current descriptions tend to
be mostly qualitative and for the less common subtypes, data is sparse.

Results

Seventy-five patients (23 ADEM and 52 AE) were identified. ADEM patients had a higher percentage of abnormal magnetic resonance imaging (MRI) findings (100% vs. 60.8%; p < 0.001) and a shorter time from symptom onset to diagnosis (6 vs. 14 days; p = 0.024). Oligoclonal bands, serum and cerebrospinal fluid (CSF) inflammatory indices were notably higher in AE patients. Nearly all patients received corticosteroids followed by plasmapheresis (PLEX) or intravenous immunoglobulin (IVIG) as first-line therapies, and treatment strategies did not differ significantly between groups. Second-line immune therapies were commonly employed in AE patients. Finally, AE patients had non-significant trends toward longer hospital lengths of stay (21 vs. 13 days) and a higher percentage of neurological disability (mRS greater than 2) at hospital discharge (59.6% vs. 34.8%).

Conclusions

Although ADEM and AE patients may have similar presenting symptoms, we found significant differences in frequency of imaging findings, symptom duration, laboratory and CSF profiles which can assist in distinguishing between the diagnoses. Patients in both groups were treated with a combination of immunomodulating therapies and neurological disability was common at hospital discharge.

Highlights

Decreased consciousness, ICU admission, a higher Neutrophil-to-lymphocyte ratio (NLR), and CSF protein are related to the integrity of the BBB in anti-NMDAR encephalitis patients.

Highlights 

Here, we review the current advances of prognosis-related research from the clinical manifestations of the disease and auxiliary examinations such as EEG, magnetic resonance imaging (MRI), 18F fluorodeoxyglucose positron emission tomography (FDG-PET), and antibody measurement. In addition, we also discuss the impact of different treatment options on prognosis. In-depth research on the prognosis of patients with anti-NMDAR encephalitis will contribute to a better understanding of this disease, leading to better treatments options and, ultimately, a better prognosis.

We found that NMDARE had a severe impact on the developing brain of children, resulting in brain volume loss and failure of age‐expected brain growth over time.  Further analyses of our pediatric patients revealed reduced cortical and deep gray matter volume with reduced volumes of hippocampus, thalamus, and basal ganglia. This is in line with findings from adult NMDARE patients that identified atrophy and impaired functional connectivity of the hippocampus that correlated with memory impairment. Interestingly, recent studies showed that many children similarly suffer from significant cognitive impairment following NMDARE, suggesting that the hippocampal volume loss found in our study might associate with impaired cognitive recovery.  Future studies are therefore warranted to assess the relationship of MRI changes and persistent cognitive deficits in pediatric NMDARE.

Conclusion In patients with AE, mechanical ventilation, sepsis, and autonomic dysregulation appear to indicate longer or incomplete convalescence. Classic ICU complications better serve as prognostic markers than the individual subtype of AE. Increased awareness and effective management of these AE-related complications are warranted, and further prospective studies are needed to confirm our findings and to develop specific strategies for outcome improvement.