Pharmacologic Treatment and Early Rehabilitation Outcomes in Pediatric Patients With Anti-NMDA Receptor Encephalitis.

OBJECTIVES: To describe the immunotherapy and pharmacologic treatments administered to pediatric patients with N-methyl-D-aspartate receptor encephalitis (NMDARE) during inpatient rehabilitation as well as to examine clinical and demographic variables associated with early functional outcomes. DESIGN: Retrospective chart review and post hoc analysis. SETTING: Pediatric inpatient rehabilitation unit. PARTICIPANTS: Pediatric patients (N=26; mean age, 10.79±5.17y) admitted to an inpatient rehabilitation unit with a confirmed diagnosis of NMDARE. INTERVENTIONS: Inpatient rehabilitation; pharmacologic treatments. MAIN OUTCOME MEASURE: FIM for Children (WeeFIM) Developmental Functional Quotient (DFQ). RESULTS: All patients received first-line immunotherapies to treat NMDARE, and 69% also received second-line immunotherapies. Patients were prescribed an average of 8 medications for symptom management (range, 3-15 per patient), most often for the treatment of agitation (100%), psychiatric symptoms (92%), and seizures (65%). Sixty-five percent of patients demonstrated an improvement in Total WeeFIM DFQ over the course of inpatient rehabilitation, with 35% demonstrating limited to no change in Total WeeFIM DFQ ("unfavorable early outcome"). Those with unfavorable early outcome were significantly younger than those showing more favorable outcome. Pharmacologic treatment for seizures, movement disorders, and decreased arousal or level of consciousness were each associated with unfavorable early outcome independent of age differences. CONCLUSION: Findings highlight the symptomatic heterogeneity and polypharmacy involved in the care and treatment of patients with NMDARE, with patients receiving a variety of immunotherapies and medications for symptom management. The presence of (and treatment for) seizures, movement disorders, and deteriorated neurologic status may each be associated with poor early outcomes in this population. Further investigation is needed to better classify presentations and treatments for this disease and to determine how differences are associated with long-term outcomes.

Multistage neurorehabilitation of an adolescent with severe anti-N-methyl-D-aspartate receptor encephalitis: a case report.

We report on a 15-year-old girl with severe anti-N-methyl-D-aspartate receptor encephalitis who had initial poor prognostic factors. We delineate the unique challenges faced in the rehabilitation of our patient including sleep disruption and food aversion. After 20 months of hospitalization and intensive rehabilitation, there was a significant improvement in functional abilities and self-care skills. However, she had residual neurocognitive deficits, visual perceptual, and motor coordination difficulties that continued to improve after discharge, attesting to the need for long-term rehabilitation. The case showed the need for a coordinated multidisciplinary approach, with both targeted therapies and neuropharmacology, tailored to facilitate the different stages of recovery unique to anti-N-methyl-D-aspartate receptor encephalitis patients.

Early Functional Outcomes for Pediatric Patients Diagnosed with Anti-N-Methyl-D-Aspartate Receptor Encephalitis during Inpatient Rehabilitation.

OBJECTIVE: The aims of the current study were to characterize the demographic and clinical presentation of pediatric patients diagnosed with anti-N-methyl-D-aspartate receptor encephalitis who require inpatient rehabilitation, to examine early functional outcomes, and to investigate predictors of early recovery. DESIGN: A retrospective chart review was conducted for 27 pediatric patients diagnosed with anti-N-methyl-D-aspartate receptor encephalitis who received intensive inpatient neurorehabilitation. RESULTS: On average, patients were 10.6 yrs of age (range, 2-18 yrs) at the time of symptom onset. Average time to treatment from symptom onset was 27.2 days (range, 5-91 days). Patients displayed significant improvements between admission and discharge Functional Independence Measure for Children (WeeFIM) Developmental Functional Quotient (DFQ) scores across patients (P < 0.01). Mean Functional Independence Measure for Children Total Developmental Functional Quotient score at admission was 28.6 (range, 15.0-62.6) and at discharge was 54.3 (range, 14.2-91.9). Younger age at onset, seizures, and number of treatments received were associated with worse functional outcomes at discharge. Time to initiate treatment was not found to be associated with early functional outcomes. CONCLUSION: Pediatric patients diagnosed with anti-N-methyl-D-aspartate receptor encephalitis displayed significant functional gains during inpatient rehabilitation, despite persistent functional deficits at discharge, suggesting the need for ongoing monitoring and intervention. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to (1) Recognize the clinical presentation of anti-N-methyl-D-aspartate receptor encephalitis in pediatric patients, (2) Appreciate the role of rehabilitation in the care of the pediatric patient with anti-N-methyl-D-aspartate receptor encephalitis, and (3) Identify demographic and clinical variables that predict poor functional outcomes after rehabilitation in pediatric patients with anti-N-methyl-D-aspartate receptor encephalitis. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The Challenge of Integrating Care in Dual Diagnosis; Anti-NMDA-Receptor Encephalitis; Presentation And Outcome In 3 Cases Referred For Complex Specialist Rehabilitation Services.

The successful implementation of an integrated care pathway (ICP) for any given condition is a challenge. Even more challenging is successful ICP implementation for individuals who have multiple co-morbidities. This is further compounded when there are dual mental health and physical disabilities that require integrated working across multiple disciplines, specialties, institutions and organisations. Anti-NMDA-Receptor encephalitis (aNMDARe) is a relatively new diagnostic entity with patients typically presenting with significant psychiatric symptoms followed by progressive neurological deterioration. In this case series, we describe 3 cases of females with aNMDARe who were referred for complex specialist rehabilitation (CSR) to The National Rehabilitation Hospital. CSR is the total active care of patients with a disabling condition, and their families, by a multi-professional team who have undergone recognised specialist training in rehabilitation, led /supported by a consultant trained and accredited in rehabilitation medicine (RM). These services provide for patients with highly complex rehabilitation needs that are beyond the scope of local services. In these cases, referral to CSR resulted in the construction of a bespoke integrated care pathway (ICP) that transcended the barriers between primary, secondary and tertiary care and across the boundaries of physical and mental health. A care pathway is a complex intervention for the mutual decision-making and organisation of care processes Rehabilitation services acted as the coordinator of services in these cases to ensure implementation of the care plan and to ensure successful transitions of care and supported local specialist and general teams in the management of these complex cases.

Autoimmune anti-N-methyl-D-aspartate receptor encephalitis - the current state of knowledge based on a clinical case.

The aim of this article is to conduct an overview of the current state of knowledge about patients presenting anti-Nmethyl- D-aspartate receptor encephalitis associated with neoplastic process, as well as diagnosis and treatment. This disease concerns mainly young women and correlates with ovarian teratoma. Most important problems seems to be the difficulties in making a proper diagnosis ensuing from the rarity of this syndrome, the period from the appearance the first symptoms to starting treatment and the correct handling of intensive care complications. There are only a few articles describing severe, complicated cases of this type of encephalitis, requiring treatment in an intensive care unit.

Pediatric Herpes Simplex Virus Encephalitis Complicated by N-Methyl-D-aspartate Receptor Antibody Encephalitis.

N-methyl-D-aspartate receptor antibodies (NMDAR-Abs) can contribute to neurological relapse after herpes simplex virus encephalitis (HSE). We describe a child with NMDAR-Ab encephalitis after HSE, which was recognized and treated early. We discuss the case in the context of existing reports, and we propose a modified immunotherapy strategy to minimize risk of viral reactivation.

Rehabilitation following anti-NMDA encephalitis.

BACKGROUND: Anti-NMDA (N-methyl D-Aspartate) encephalitis is an autoimmune disorder of the central nervous system which presents acutely with seizures, disturbances in consciousness and behavioural change. Although there is an increasing amount of information about the diagnosis and acute treatment strategies, little is known about rehabilitation needs and outcomes for this patient group. CASE REPORT: This study presents a 52-year old woman who initially presented with generalized seizures and drowsiness. She was admitted to hospital where autoimmune encephalitis was diagnosed based on a positive serum anti-NMDA antibody titre. When medically stabilized, she was transferred to a specialist neurorehabilitation unit for ongoing care. Her main clinical issues were around behavioural disturbance, communication, continence, mobility and cognition. A multi-disciplinary approach was taken to her problems and she was eventually discharged back to community living having made substantial improvements in all domains of functioning. The clinical challenges encountered throughout her rehabilitation and the approach to ameliorating these is described. CONCLUSION: Although having a relatively rare diagnosis, the specific rehabilitation needs of this patient were met through an existing specialist neurorehabilitation service. A broader case series is required to determine needs and effective approaches across this patient group as a whole.

Long term rehabilitation management and outcome of anti-NMDA receptor encephalitis: case reports.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an auto immune-disorder. It is a life threatening condition that typically presents with viral illness, headaches, severe psychiatric symptoms, seizures, behavioural changes, decreasing levels of unconsciousness and progressive unresponsiveness, cognitive impairment, abnormal movements (e.g., dyskinesia), ataxia and hypoventilation. OBJECTIVE: This paper describes the long term outcome and rehabilitation management of patients with NMDAR encephalitis and highlights the diverse outcome of this condition and the unique and individual long term management needs associated with this disorder. METHODS: This is a case report study of three different patients with NMDAR encephalitis. All three cases are young women, two of whom presented with ovarian teratoma. Patient KH is the most impaired and was resident in a slow stream rehabilitation care home and presented with challenging behaviour. Patients RM and OA both lived in the community and presented with similar anxieties but diverse levels of cognition and motivation. A review of the literature is provided summarizing the disorder, interventions, management and challenges of this varied and complex condition. Standard neuropsychological tests and questionnaires to assess community integration (BICRO-39), quality of life (QOLIBRI-OS) and mood (HADS) were administered. RESULTS: Positive outcomes were achieved for all three patients using a variety of interventions which included behavioural management, family psycho-education and an integrated holistic multi-disciplinary team community approach. Memory and executive deficits were persistent in the long term and severity of impairments showed wide variability between patients. Emotional distress and behavioural difficulties were prominent and persistent and had a pronounced impact on rehabilitation. Continence issues were also a major factor impacting on the rehabilitation. CONCLUSIONS: Long term integrated and multi-disciplinary input by a variety of therapies and health disciplines is required in order to improve the long term outcome and quality of life for NMDAR patients and their families, and ultimately leads to improved positive outcomes. Each of these cases had markedly differing cognitive profiles suggesting that in the context of long term rehabilitation outcome, cognition may have less valence than emotional and behavioural factors. Guidelines and standardised procedures for ethical issues and counselling for iatrogenic infertility should be developed and integrated into long term programmes of rehabilitation care.

The rehabilitation of children with anti-N-methyl-D-aspartate-receptor encephalitis: a case series.

Anti-N-methyl-D-aspartate (NMDA)-receptor encephalitis is a serious, complex, and potentially fatal disease in children. Children with this condition frequently present with altered mental status, rapid functional deterioration, and seizures. Despite aggressive treatment with immune therapy such as corticosteroids, intravenous immunoglobin, and plasmapheresis, children often need extensive rehabilitative services and can be left with lasting deficits. In this case series, we report on six known consecutive pediatric cases of N-methyl-D-aspartate-receptor antibody encephalitis in Northern California requiring comprehensive inpatient rehabilitation. The children presented with a variety of symptoms and had waxing and waning clinical courses. All children progressed well through their rehabilitation programs but were discharged home with persistent functional deficits. At follow-up, all but one child had lasting deficits. Because of the complicated management and extensive rehabilitation needs of children with anti-N-methyl-D-aspartate-receptor encephalitis, physiatrists and other rehabilitation providers should be knowledgeable about this complex condition.