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1.
Tijdschr Psychiatr ; 66(4): 221-225, 2024.
Artículo en Holandés | MEDLINE | ID: mdl-38650533

RESUMEN

Anti-NMDA receptor encephalitis is an auto-immune disorder often presenting with non-specific and heterogeneous neuropsychiatric symptoms at onset. This complicates a quick and accurate diagnosis. However, a tardy diagnosis has a negative impact on morbidity and mortality. We report about a patient with the clinical presentation of a psychotic depression, who was diagnosed with anti-NMDA receptor encephalitis only after a thorough diagnostic work-up. Neurological symptoms were wrongly attributed to the psychiatric syndrome or considered as side-effects of its treatment. We present an overview of clinical aspects of the disorder, distinctive psychiatric symptoms, diagnostic tools, treatment and prognosis.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Humanos , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Diagnóstico Diferencial , Pronóstico , Femenino , Diagnóstico Tardío , Masculino
2.
Clin Child Psychol Psychiatry ; 29(2): 648-660, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37915202

RESUMEN

OBJECTIVES: Explore psychosocial outcome and impact of persisting deficits on quality of life (QoL) and global functioning after anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) in children and adolescents. METHODS: Four female patients (age 7-16y) and their caregivers participated in the study. Information was collected from the medical records and the caregivers via a questionnaire. Both the patients and their caregivers were interviewed by means of the structured clinical interview for DSM-5 disorders, junior version (SCID-5 junior). CGAS and mRS scores were defined and the Pediatric Quality of Life Inventory (PedsQL) was used to assess quality of life of patients and caregivers. RESULTS AND CONCLUSION: After the acute phase of the disease patients go through a post-acute phase in which several persisting physical, cognitive and psychiatric symptoms gradually resolve during the following months to a year. In long-term follow up these symptoms partly resolved, but deficits persisted on several domains. Psychiatric symptoms, fatigue and mild cognitive deficits were present in three out of four patients at current assessment. In three patients their academic trajectory was altered. These deficits can have an impact on the quality of life and the global functioning of the patients and caregivers.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Trastornos Mentales , Niño , Humanos , Adolescente , Femenino , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Calidad de Vida , Progresión de la Enfermedad , Cuidadores
3.
J Neurol ; 270(1): 402-412, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36112199

RESUMEN

The objective of this study was to describe neuropsychological functioning and associated medical features in pediatric patients with anti-NMDA receptor encephalitis (anti-NMDARE). Retrospective data were collected from electronic medical records and neuropsychological reports of 15 children and adolescents with cerebral spinal fluid antibody-confirmed anti-NMDARE who were 7-21 years old at the time of the neuropsychological evaluation. The median time between treatment initiation for anti-NMDARE and neuropsychological testing was 228 days (IQR 431, range 41-927). Consistent with the limited literature, this pediatric sample with anti-NMDARE generally had average IQs, but had scores falling in the low average range on tests of verbal and visual memory as well as aspects of executive functioning (set shifting and phonemic verbal fluency). Other relative weaknesses were observed in visuo-constructional ability and reading comprehension. Future prospective studies are needed to replicate these data and explore disease and treatment variables that reduce or exacerbate the risk for neuropsychological sequelae, while longitudinal analyses are required to better characterize academic, vocational, and social outcomes.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Estudios Retrospectivos , Cognición , Función Ejecutiva , Memoria , Pruebas Neuropsicológicas
4.
Expert Rev Neurother ; 22(2): 155-167, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35130814

RESUMEN

INTRODUCTION: Autoimmune encephalitis (AIE) is a group of immune-mediated inflammatory processes of the brain with marked psychiatric features. Although relatively rare, they might offer difficult differential diagnosis with psychiatric conditions, especially catatonia and psychotic syndromes. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is the most common AIE, presenting with psychiatric syndromes in 90% of cases. The associated psychopathology is complex, pleomorphic, and best characterized when there is involvement of a psychiatrist in the assessment. AREAS COVERED: This text will review the main aspects of AIE to psychiatrists and/or neuropsychiatrists. EXPERT OPINION: Immune system dysfunction has been implicated in the pathophysiology of psychiatric symptoms and disorders. The use of diagnostic criteria for possible AIE, especially when specific antibodies of AIE are not available, allows early diagnosis and prompt treatment which are associated with better clinical outcomes. The study of the psychiatric aspects of AIE can broaden our knowledge of the underlying mechanisms of various psychiatric manifestations.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Catatonia , Enfermedad de Hashimoto , Trastornos Mentales , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Catatonia/complicaciones , Enfermedad de Hashimoto/diagnóstico , Enfermedad de Hashimoto/psicología , Humanos , Trastornos Mentales/complicaciones , Psiquiatría , Receptores de N-Metil-D-Aspartato
5.
Eur Arch Psychiatry Clin Neurosci ; 272(3): 477-482, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34272976

RESUMEN

Autoimmune encephalitis (AE) can present like a psychiatric disorder. We aimed to illustrate the psychiatric manifestations, course and management of AE in a paediatric cohort. Neuropsychiatric symptoms, investigations and treatment were retrospectively retrieved in 16 patients (mean age 11.31, SD 2.98) with an AE diagnosis at the liaison psychiatry services in two UK tertiary paediatric centres. Psychiatric presentation was characterised by an acute polysymptomatic (predominantly agitation, anger outbursts/aggressiveness, hallucinations, and emotional lability) onset. Antipsychotics produced side effects and significant worsening of symptoms in four cases, and benzodiazepines were commonly used. This psychiatric phenotype should make clinicians suspect the diagnosis of AE and carefully consider use of treatments.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Enfermedad de Hashimoto , Trastornos Mentales , Adolescente , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Encefalitis Antirreceptor N-Metil-D-Aspartato/terapia , Niño , Alucinaciones , Enfermedad de Hashimoto/diagnóstico , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/etiología , Estudios Retrospectivos
6.
Psychiatr Pol ; 56(6): 1315-1326, 2022 Dec 31.
Artículo en Inglés, Polaco | MEDLINE | ID: mdl-37098200

RESUMEN

In recent years, the frequency of diagnosing autoimmune encephalitis has increased significantly, both in the population of adults and children and adolescents. This fact is undoubtedly related to the dynamic development of new diagnostic methods, as well as the progress of medical knowledge. A particular type of this condition is anti-NMDA receptor encephalitis. Due to the presence of psychiatric symptoms in this disease, psychiatrists are often the first specialists who treat a patient with the above diagnosis. Differential diagnosis is extremely difficult and primarily based on the history and presence of typical clinical symptoms. Therefore, based on a narrative review of the literature on the subject searched by the PubMed, EMBASE, and Cochrane library databases from 2007-2021 with the keywords "anti-NMDAR encephalitis", "children", and "adolescents", the author described the characteristic course of the disease, diagnostic methods used to confirm the diagnosis, and presents current treatment guidelines. Due to high prevalence, anti-NMDA receptor encephalitis is a diagnosis that should be considered in the differential diagnosis in everyday psychiatric practice.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Trastornos Mentales , Adulto , Adolescente , Humanos , Niño , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/terapia , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Trastornos Mentales/diagnóstico , Diagnóstico Diferencial , Prevalencia
7.
Rev Alerg Mex ; 68(4): 251-263, 2021.
Artículo en Español | MEDLINE | ID: mdl-34904561

RESUMEN

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a potentially lethal clinical entity that belongs to the group of antibody-mediated encephalitis against synaptic proteins. It shows IgG antibodies against the NR1 subunit of the NMDA receptor (NMDA-R), which have been associated with psychiatric and neurological symptoms that develop in stages in the course of the disease. The predominance of neuropsychiatric symptoms in the early stages of the disease results in an increased number of patients that search for psychiatric evaluation as their first contact with the health system. For this reason, it is vital for physicians to recognize this entity as an important differential diagnosis in their clinical practice because, despite the severity of this condition, more than 75 % of patients achieve a substantial recovery with appropriate and timely treatment. We present a review of the literature on this disease, with special emphasis on the neuropsychiatric aspects.


La encefalitis por anticuerpos contra el receptor anti-N-metil-D-aspartato (NMDA) es una entidad clínica potencialmente letal perteneciente al grupo de las encefalitis mediadas por anticuerpos contra proteínas sinápticas. En esta se demuestran anticuerpos IgG contra el receptor de NMDA (NMDAr), asociados con síntomas psiquiátricos y neurológicos que se desarrollan por estadios en el curso de la enfermedad. El predominio de síntomas neuropsiquiátricos en las etapas tempranas provoca que un elevado porcentaje de pacientes busquen evaluación psiquiátrica como un primer contacto con el sistema de salud. Por esta razón, es vital que los médicos reconozcan esta entidad como un diagnóstico diferencial importante en la práctica clínica, puesto que, a pesar de la gravedad de esta condición, más de 75 % de los pacientes logra una recuperación sustancial con un tratamiento adecuado y oportuno. Presentamos una revisión de la literatura sobre esta enfermedad, con especial énfasis en los aspectos neuropsiquiátricos.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Autoanticuerpos , Diagnóstico Diferencial , Humanos , Inmunoglobulinas , Receptores de N-Metil-D-Aspartato
8.
Ann Neurol ; 90(6): 949-961, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34595771

RESUMEN

OBJECTIVE: Cognitive dysfunction is a core symptom of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, but detailed studies on prevalence, characteristics of cognitive deficits, and the potential for recovery are missing. Here, we performed a prospective longitudinal study to assess cognitive long-term outcome and identify clinical predictors. METHODS: Standardized comprehensive neuropsychological assessments were performed in 43 patients with NMDAR encephalitis 2.3 years and 4.9 years (median) after disease onset. Cognitive assessments covered executive function, working memory, verbal/visual episodic memory, attention, subjective complaints, and depression and anxiety levels. Cognitive performance of patients was compared to that of 30 healthy participants matched for age, sex, and education. RESULTS: All patients had persistent cognitive deficits 2.3 years after onset, with moderate or severe impairment in >80% of patients. Core deficits included memory and executive function. After 4.9 years, significant improvement of cognitive function was observed, but moderate to severe deficits persisted in two thirds of patients, despite favorable functional neurological outcomes (median modified Rankin Scale = 1). Delayed treatment, higher disease severity, and longer duration of the acute phase were predictors for impaired cognitive outcome. The recovery process was time dependent, with greater gains earlier after the acute phase, although improvements were possible for several years after disease onset. INTERPRETATION: Cognitive deficits are the main contributor to long-term morbidity in NMDAR encephalitis and persist beyond functional neurological recovery. Nonetheless, cognitive improvement is possible for several years after the acute phase and should be supported by continued cognitive rehabilitation. Cognition should be included as an outcome measure in future clinical studies. ANN NEUROL 2021;90:949-961.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Atención/fisiología , Cognición/fisiología , Disfunción Cognitiva/complicaciones , Memoria/fisiología , Adolescente , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Disfunción Cognitiva/psicología , Función Ejecutiva/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estudios Prospectivos , Adulto Joven
9.
Hosp Pediatr ; 11(7): 743-750, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34103402

RESUMEN

OBJECTIVES: Patients with autoimmune encephalitis (AE) often present with symptoms that are broadly characterized as psychiatric or behavioral, yet little attention is given to the precise symptomatology observed. We sought to more fully define the psychiatric symptoms observed in patients with anti-N-methyl-D-aspartate receptor (NMDAR), anti-glutamic-acid-decarboxylase 65 (GAD65), and anti-voltage-gated-potassium-channel complex (VGKC) antibody-mediated AE using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition nomenclature. METHODS: We present a case series (n = 25) using a retrospective chart review of 225 patients evaluated for AE in a tertiary care academic medical center between 2014 and 2018. The included patients were ≤18 years old with anti-NMDAR AE (n = 13), anti-GAD65 AE (n = 7), or anti-VGKC AE (n = 5). The frequency of neuropsychiatric symptoms present at the onset of illness and time to diagnosis were compared across groups. RESULTS: Psychiatric symptoms were seen in 92% of patients in our cohort. Depressive features (72%), personality change (64%), psychosis (48%), and catatonia (32%) were the most common psychiatric symptoms exhibited. On average, patients experienced impairment in ≥4 of 7 symptom domains. No patients had isolated psychiatric symptoms. The average times to diagnosis were 1.7, 15.5, and 12.4 months for anti-NMDAR AE, anti-GAD65 AE, and anti-VGKC AE, respectively (P < .001). CONCLUSIONS: The psychiatric phenotype of AE in children is highly heterogenous. Involving psychiatry consultation services can be helpful in differentiating features of psychosis and catatonia, which may otherwise be misidentified. Patients presenting with psychiatric symptoms along with impairments in other domains should prompt a workup for AE, including testing for all known antineuronal antibodies.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Enfermedad de Hashimoto , Adolescente , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Catatonia/etiología , Niño , Encefalitis , Enfermedad de Hashimoto/complicaciones , Enfermedad de Hashimoto/psicología , Humanos , Fenotipo , Trastornos Psicóticos/etiología , Estudios Retrospectivos
10.
Neurology ; 97(1): e61-e75, 2021 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-33980703

RESUMEN

OBJECTIVES: To report the neuropsychiatric features and frequency of NMDA receptor (NMDAR) and other neuronal immunoglobulin G antibodies in patients with first episode psychosis (FEP) and to assess the performance of reported warning signs and criteria for autoimmune psychosis (AP). METHODS: This was a prospective observational study of patients with FEP assessed for neuropsychiatric symptoms, serum and CSF neuronal antibodies (brain immunohistochemistry, cell-based assays, live neurons), and warning signs and criteria of AP. Previous autoimmune FEP series were reviewed. RESULTS: One hundred five patients were included; their median age was 30 (range 14-75) years, and 44 (42%) were female. None had neuronal antibodies. Two of 105 (2%) had CSF pleocytosis, 4 of 100 (4%) had brain MRI abnormalities, and 3 of 73 (4%) EEG alterations. Thirty-four (32%) and 39 (37%) patients fulfilled 2 sets of warning signs of AP, and 21 (20%) fulfilled criteria of possible or probable AP, yet none developed AP. The cause of FEP was psychiatric in 101 (96%) and nonpsychiatric in 4 (4%). During this study, 3 patients with psychosis caused by anti-NMDAR encephalitis were transferred to our center; 2 did not meet criteria for possible AP. Of 1,159 reported patients with FEP, only 7 (1%) had CSF studies; 36 (3%) had serum NMDAR antibodies (without definite diagnosis of AP), and 4 had CSF NMDAR antibodies (3 classic anti-NMDAR encephalitis and 1 with isolated psychiatric features). CONCLUSIONS: NMDAR antibodies were not found in patients with FEP unless they had anti-NMDAR encephalitis. Warning signs and criteria for AP have limited utility when neurologic symptoms are absent or paraclinical tests are normal. A diagnostic algorithm for autoimmune FEP is provided.


Asunto(s)
Trastornos Psicóticos/líquido cefalorraquídeo , Trastornos Psicóticos/psicología , Adolescente , Adulto , Anciano , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Anticuerpos/análisis , Autoanticuerpos/análisis , Enfermedades Autoinmunes/líquido cefalorraquídeo , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/psicología , Electroencefalografía , Femenino , Humanos , Inmunoglobulina G/inmunología , Inmunohistoquímica , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Trastornos Psicóticos/inmunología , Receptores de N-Metil-D-Aspartato/inmunología , Adulto Joven
11.
CNS Neurosci Ther ; 27(6): 652-663, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33713553

RESUMEN

AIMS: To explore large-scale brain network alterations and examine their clinical and neuropsychological relevance in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: Twenty-four patients with anti-NMDAR encephalitis and 26 matched healthy controls (HCs) were enrolled in our study. Based on the multimodal MRI dataset, individual morphological, structural, and functional brain networks were constructed and compared between the two groups at multiple levels. The associations with clinical/neuropsychological variables and the discriminant ability of significant alterations were further studied. RESULTS: Multimodal network analysis revealed that anti-NMDAR encephalitis mainly affected morphological and structural networks, but subtle alterations were observed in functional networks. Intriguingly, decreased network local efficiency was observed for both morphological and structural networks and increased nodal centrality in the lateral orbital gyrus was convergently observed among the three types of networks in the patients. Moreover, the alterations, particularly those from structural networks, accounted largely for cognitive deficits of the patients and could distinguish the diseased individuals from the HCs with excellent performance (area under the curve =0.933). CONCLUSIONS: The current study provides a comprehensive view of characteristic multimodal network dysfunction in anti-NMDAR encephalitis, which is crucial to establish new diagnostic biomarkers and promising therapeutic targets for the disease.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico por imagen , Encefalitis Antirreceptor N-Metil-D-Aspartato/patología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/patología , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Encéfalo/fisiopatología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/psicología , Imagen de Difusión Tensora , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Imagen Multimodal , Pruebas Neuropsicológicas , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/patología , Corteza Prefrontal/fisiopatología , Adulto Joven
12.
Neurosci Lett ; 746: 135650, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33485991

RESUMEN

OBJECTIVE: Serum creatinine (SCR) has been shown to be associated with many neurodegenerative diseases. In this study, we investigated the relationship between SCR levels and the incidence of psychiatric symptoms in patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. METHODS: The SCR levels were tested in 69 patients with anti-NMDAR encephalitis at admission. Clinical characteristics and blood and CSF parameters were compared between the group of patients with psychiatric symptoms (P + group) and the group of those without psychiatric symptoms (P- group). The association between SCR and the incidence of psychiatric symptoms was determined by multivariate-adjusted linear regression analyses. RESULTS: The SCR levels in the P + group were significantly lower than those in the P- group (P < 0.001). In the female subgroup, the SCR levels in the P + group were significantly lower compared to the P- group (P < 0.001), whereas in the male subgroup, the SCR levels did not differ between the two groups (P = 0.084). Furthermore, the highest SCR tercile overall had a significantly lower incidence of psychiatric symptoms than the lowest tercile (P < 0.001), and a significant negative correlation between the SCR levels and the occurrence of psychiatric symptoms was observed (r = -0.392, P < 0.001). Multivariate logistic regression analysis showed that the association was independent after adjusting for age, cystatin C and the modified Rankin Scale (mRS) score (P = 0.001). A similar result was found in the female subgroup (P = 0.010), but not in the male subgroup (P = 0.225). CONCLUSION: Our study indicated that the SCR level was negatively correlated with incidence of psychiatric symptoms in female patients, and higher SCR level could be a protective factor for psychiatric symptoms in female patients with anti-NMDAR encephalitis.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/sangre , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Creatinina/sangre , Trastornos Mentales/sangre , Trastornos Mentales/psicología , Caracteres Sexuales , Adolescente , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Biomarcadores/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Trastornos Mentales/diagnóstico , Persona de Mediana Edad , Adulto Joven
13.
Psychol Med ; 51(3): 435-440, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-31739809

RESUMEN

BACKGROUND: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disorder which requires multi-disciplinary treatment including immunomodulation therapy. First presentation is most commonly to psychiatric services and continuing psychiatric care is required to treat disabling symptoms, such as behaviour disturbance, psychosis and catatonia. There is minimal available evidence to guide symptomatic treatment and concern for increased sensitivity to antipsychotics complicates traditional approaches. METHODS: All cases of cerebrospinal fluid positive anti-NMDAR encephalitis tested in Queensland, Australia were identified. Demographic, clinical and therapeutic data were collected and reviewed by two independent clinicians. Pre-specified variables reflecting possible treatment side effects were compared. RESULTS: The majority of the 30 cases (83%) had early psychiatric symptoms and were treated with antipsychotics (67%), average daily olanzapine equivalence dose of 11.5 mg, prior to immunomodulation therapy. Although there was an 88% reduction in cases with aggression, there was little improvement in psychosis, affective symptoms or catatonia with antipsychotics alone. In the cases with psychiatric symptoms, there was no significant difference in the rate of occurrence of neurological and autonomic symptoms between cases prescribed and not prescribed antipsychotics. CONCLUSIONS: Psychiatric input is imperative for both acute and longer-term management of anti-NMDAR encephalitis. Primary symptomatic treatment should remain immunotherapy and surgery. Antipsychotic medications have particular value in managing agitation and aggression. Potential side effects from antipsychotic treatment are difficult to differentiate from progression of anti-NMDAR encephalitis but there was no evidence in this cohort of increased antipsychotic sensitivity. Treatment with psychotropic medication should be individualised and adjusted during the course of the illness.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Antipsicóticos/uso terapéutico , Catatonia/tratamiento farmacológico , Trastornos Psicóticos/tratamiento farmacológico , Adulto , Agresión/efectos de los fármacos , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Catatonia/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Psicóticos/etiología , Queensland , Estudios Retrospectivos , Adulto Joven
14.
Nat Commun ; 11(1): 4250, 2020 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-32843635

RESUMEN

A mechanistic understanding of core cognitive processes, such as working memory, is crucial to addressing psychiatric symptoms in brain disorders. We propose a combined psychophysical and biophysical account of two symptomatologically related diseases, both linked to hypofunctional NMDARs: schizophrenia and autoimmune anti-NMDAR encephalitis. We first quantified shared working memory alterations in a delayed-response task. In both patient groups, we report a markedly reduced influence of previous stimuli on working memory contents, despite preserved memory precision. We then simulated this finding with NMDAR-dependent synaptic alterations in a microcircuit model of prefrontal cortex. Changes in cortical excitation destabilized within-trial memory maintenance and could not account for disrupted serial dependence in working memory. Rather, a quantitative fit between data and simulations supports alterations of an NMDAR-dependent memory mechanism operating on longer timescales, such as short-term potentiation.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/fisiopatología , Memoria a Corto Plazo/fisiología , Esquizofrenia/fisiopatología , Sinapsis/fisiología , Adolescente , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Femenino , Humanos , Masculino , Modelos Neurológicos , Red Nerviosa/fisiopatología , Plasticidad Neuronal , Corteza Prefrontal/fisiopatología , Receptores de N-Metil-D-Aspartato/fisiología , Psicología del Esquizofrénico , Adulto Joven
15.
Psychosomatics ; 61(5): 456-466, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32507506

RESUMEN

BACKGROUND: The novelty of anti-NMDA receptor encephalitis, for which somatic treatments have only recently been developed, has led to a lack of information on assessment and treatment of its variable behavioral manifestations. METHOD: In this article, we discuss 4 challenging cases of anti-NMDAR encephalitis, focusing on the importance of a multidisciplinary approach to identification and management of the disorder and the necessity of close collaboration in the acute hospital setting for management of the behavioral symptoms. CONCLUSION: The cases we discuss highlight some of the medication and nonpharmacologic treatment strategies that may facilitate management of psychiatric symptoms, both while the medical workup is ongoing and after the diagnosis has been confirmed.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Trastornos Psicóticos/etiología , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Femenino , Humanos , Persona de Mediana Edad
16.
Neurology ; 95(6): e671-e684, 2020 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-32576635

RESUMEN

OBJECTIVE: To describe the sleep disorders in anti-NMDA receptor encephalitis (anti-NMDARe). METHODS: Patients recovering from anti-NMDARe were invited to participate in a prospective observational single-center study including comprehensive clinical, video-polysomnography (V-PSG) sleep assessment, and neuropsychological evaluation. Age- and sex-matched healthy participants served as controls. RESULTS: Eighteen patients (89% female, median age 26 years, interquartile range [IQR] 21-29 years) and 21 controls (81% female, median age 23 years, IQR 18-26 years) were included. In the acute stage, 16 (89%) patients reported insomnia and 2 hypersomnia; nightmares occurred in 7. After the acute stage, 14 (78%) had hypersomnia. At study admission (median 183 days after disease onset, IQR 110-242 days), 8 patients still had hypersomnia, 1 had insomnia, and 9 had normal sleep duration. Patients had more daytime sleepiness than controls (higher Barcelona Sleepiness Index, p = 0.02, and Epworth Sleepiness Score, p = 0.04). On V-PSG, sleep efficiency was similar in both groups, but patients more frequently had multiple and longer confusional arousals in non-REM (NREM) sleep (videos provided). In addition, 13 (72%) patients had cognitive deficits; 12 (67%) had psychological, social, or occupational disability; and 33% had depression or mania. Compared with controls, patients had a higher body mass index (median 23.5 [IQR 22.3-30.2] vs 20.5 [19.1-21.1] kg/m2; p = 0.007). Between disease onset and last follow-up, 14 (78%) patients developed hyperphagia, and 6 (33%) developed hypersexuality (2 requiring hospitalization), all associated with sleep dysfunction. CONCLUSIONS: Sleep disturbances are frequent in anti-NMDARe. They show a temporal pattern (predominantly insomnia at onset; hypersomnia during recovery), are associated with behavioral and cognitive changes, and can occur with confusional arousals during NREM sleep.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Trastornos Intrínsecos del Sueño/etiología , Adolescente , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Estudios de Casos y Controles , Niño , Trastornos de Somnolencia Excesiva/etiología , Trastornos de Somnolencia Excesiva/fisiopatología , Sueños , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Polisomnografía , Estudios Prospectivos , Trastornos del Despertar del Sueño/etiología , Trastornos del Despertar del Sueño/fisiopatología , Trastornos Intrínsecos del Sueño/fisiopatología , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología , Fases del Sueño , Sueño de Onda Lenta , Grabación en Video , Adulto Joven
17.
Epilepsy Behav ; 108: 107088, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32375094

RESUMEN

PURPOSE: The purpose of this study was to assess long-term psychosocial outcomes of anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (anti-NMDARE). METHODS: Adolescents and adults with self-reported anti-NMDARE were invited to complete an online survey distributed by relevant patient organizations. Demographic and clinical information was collected, including the diagnoses initially given for anti-NMDARE symptoms and posthospital care received. Patient-Reported Outcomes Measurement Information System (PROMIS) Psychosocial Impact Illness - Negative short form (Negative PSII) was administered to assess psychosocial outcome of anti-NMDARE. Associations between clinical factors and psychosocial outcomes were evaluated. RESULTS: Sixty-one individuals with anti-NMDARE age 15 years and above participated. Mean age was 33.7 years (standard deviation [SD]: 12.8), and participants were predominantly female (90.2%, n = 55). Mean T-score on PROMIS Negative PSII was 60.7, >1 SD higher (worse psychosocial function) than that of the provided normalized sample enriched for chronic illness (50, SD: 10). Initial misdiagnosis of anti-NMDARE symptoms was associated with decreased odds (odds ratio [OR]: 0.11, p < 0.05), and follow-up with a psychiatrist after hospitalization with increased odds (OR: 8.46, p < 0.05), of return to work/school after illness. Younger age of symptom onset and presence of ongoing neuropsychiatric issues were predictive of worse Negative PSII scores (p < 0.05). CONCLUSION: Individuals with anti-NMDARE demonstrate poor psychosocial outcomes, yet there are no current standards for long-term assessment or management of such symptoms in this population. These findings highlight the need for use of more comprehensive outcome measures that include assessment of psychosocial function and the importance of developing interventions that address this domain for individuals with anti-NMDARE.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Medición de Resultados Informados por el Paciente , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Adulto Joven
18.
Epilepsy Behav ; 108: 107066, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32375097

RESUMEN

PURPOSE: The purpose of the study was to assess care transitions and caregiver burden among caregivers of individuals with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (anti-NMDARE). METHODS: Caregivers of individuals with anti-NMDARE were recruited via patient organization websites. Demographic and clinical information as well as responses to the Care Transition Measure 15 (CTM-15) and Zarit Burden Interview (ZBI) were collected. Exploratory factor analysis (EFA) was conducted on the ZBI, and underlying constructs were analyzed for associations with the CTM-15 and clinical characteristics. RESULTS: Seventy-six caregivers participated. On the CTM-15, the top items where caregivers disagreed or strongly disagreed were the following: "when the patient left the hospital, I had a readable and easily understood written plan that described how all of their healthcare needs were going to be met" (73%), "when the patient left the hospital, I was confident that I know how to manage their health" (62%), and "when the patient left the hospital, I had all the information I needed to be able to take care of them" (58%). Worse care transitions significantly predicted higher caregiver burden scores. Mean ZBI score was 44, falling in the moderate to severe burden range. Exploratory factor analysis was conducted and found four common underlying factors associated with total score. Factor 1, the impact of caring on caregivers' personal lives (accounting for 51% of total score variance), was selected for further analysis because of its modifiable nature. Higher ZBI scores were associated with lower CTM-15 scores (p < 0.003) and the individual with anti-NMDARE not returning to driving (p < 0.002). CONCLUSION: This study identified specific elements of care transitions and caregiver burden that are not currently being addressed for individuals with anti-NMDARE. Attention to these aspects of care in the development of targeted interventions may improve outcomes in individuals with anti-NMDARE and their caregivers.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Carga del Cuidador/psicología , Cuidadores/psicología , Costo de Enfermedad , Transferencia de Pacientes/métodos , Autoinforme , Adolescente , Adulto , Anciano , Encefalitis Antirreceptor N-Metil-D-Aspartato/epidemiología , Encefalitis Antirreceptor N-Metil-D-Aspartato/terapia , Carga del Cuidador/diagnóstico , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
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