Suicidal Thoughts and Behaviors in Anti-NMDA Receptor Encephalitis: Psychopathological Features and Clinical Outcomes.

OBJECTIVE: A wide variety of neuropsychiatric symptoms are described during the acute phase of anti-N-methyl-d-aspartate receptor encephalitis (ANMDARE), including psychosis, mania, depression, and catatonia, but there are few reports on suicidal thought and behaviors in ANMDARE. To address this gap in the literature, the authors measured the presence of suicidal thoughts and behaviors among a large cohort of Mexican patients diagnosed with definite ANMDARE. METHODS: This observational and longitudinal study included patients with definite ANMDARE hospitalized at the National Institute of Neurology and Neurosurgery of Mexico between 2014 and 2021. Suicidal thoughts and behaviors were assessed before and after treatment by means of a clinical interview with relatives and a direct clinical assessment with each patient. Thoughts of engaging in suicide-related behavior and acts of suicidal and nonsuicidal self-directed violence before and during hospitalization were recorded. RESULTS: From a total sample of 120 patients who fulfilled the diagnostic criteria for definite ANMDARE, 15 patients (13%) had suicidal thoughts and behaviors during the acute phase of the disease. All 15 of these patients experienced psychosis and had suicidal ideation with intention. Three patients engaged in preparatory behaviors and seven carried out suicidal self-directed violence. Psychotic depression and impulsivity were more frequent among those patients with suicidal thoughts and behaviors than among those without any form of suicidality. Four patients engaged in self-directed violence during hospitalization. Remission was sustained in 14 of 15 patients, with suicidal ideation and self-directed violence persisting during follow-up in only one patient. CONCLUSIONS: Suicidal thoughts and behaviors are not uncommon during the acute phase of ANMDARE. On the basis of our sample, the persistence of these features after immunotherapy is rare but may be observed. A targeted assessment of suicidal risk should be strongly considered in this population.

Clinical Significance of Delirium With Catatonic Signs in Patients With Neurological Disorders.

OBJECTIVE: According to DSM-5, catatonia and delirium are mutually exclusive clinical syndromes. The investigators explored the co-occurrence of delirium and catatonia (i.e., catatonic delirium) and the clinical significance of this syndrome with a sample of neurological patients. METHODS: This prospective study with consecutive sampling included patients diagnosed with delirium at the National Institute of Neurology and Neurosurgery of Mexico. DSM-5 criteria for delirium, the Confusion Assessment Method, and the Delirium Rating Scale-Revised-98 were used to select and characterize patients. Catatonia was assessed using the Bush-Francis Catatonia Rating Scale and DSM-5 diagnostic criteria. Logistic regression analysis was performed to identify etiological factors associated with catatonic delirium. RESULTS: A total of 264 patients with delirium were included, 61 (23%) of whom fulfilled the criteria for catatonia and delirium simultaneously. Brain tumors, subarachnoid hemorrhage, acute hydrocephalus, and ischemic stroke were associated with delirium without catatonic signs. Catatonic delirium was observed among patients with encephalitis, epilepsy, brain neoplasms, and brain tuberculosis. After multivariate analysis, the association between catatonic delirium and encephalitis (both viral and anti-N-methyl-d-aspartate receptor [NMDAR]) was confirmed. CONCLUSIONS: Delirium is a common complication of neurological diseases, and it can coexist with catatonia. The recognition of catatonic delirium has clinical significance in terms of etiology, as it was significantly associated with viral and anti-NMDAR encephalitis.

A Metabolic Brain Pattern Associated With Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis causes substantial neurological disability. Autoantibodies causing encephalitis directed against the neuronal cell surface or synapse are of diagnostic importance giving the possibility of successful immunotherapy. OBJECTIVE: In this study, we aim to provide supporting evidence that brain 18F-FDG-PET may be helpful in identifying likely patterns of regional brain glucose metabolism. METHODS: Thirty-three patients (18 men and 15 women; age range of 17-55 y) with positive NMDA receptor antibody encephalitis that underwent an 18F-FDG-PET imaging examination were prospectively selected and compared with a reference group of 14 brain 18F-FDG-PET scans from healthy volunteers using voxel-based statistical analysis. Clusters of hyper- and hypo-metabolism were reported for the whole sample of patients (FWE-corrected P < 0.05), and uncorrected at P < 0.005 for a group of relapsed patients. RESULTS: Mixed metabolic patterns (focal/bilateral hypermetabolism in the temporal lobe, insula, and cerebellum; associated with severe bilateral hypometabolism in the occipital and parietal lobes) were found. CONCLUSIONS: Our findings suggest that 18F-FDG-PET should be included as an imaging tool when assessing affected patients in the clinical workup to rule out anti-NMDA encephalitis and help determine the most effective treatment.

Characterisation and outcome of neuropsychiatric symptoms in patients with anti-NMDAR encephalitis.

BACKGROUND: Encephalitis due to anti-N-methyl-D-aspartate receptor antibodies (ANMDARE) is the most frequent immune-mediated encephalitis. It is distinguished by the subacute onset of neuropsychiatric symptoms. OBJECTIVE: To evaluate the characteristic neuropsychiatric symptoms and their outcome in patients diagnosed with ANMDARE. METHODS: This was a prospective, longitudinal study in patients with a diagnostic suspicion of ANMDARE that presented to the National Institute of Neurology from March 2018 to February 2019. A comparative analysis of two groups (positive N-methyl-D-aspartate receptor [NMDAR] vs. negative NMDAR antibodies in cerebrospinal fluid [CSF]) was done on admission and at discharge. Neuropsychiatric systematic assessments included the Neuropsychiatric Inventory Questionnaire, the Bush Francis Catatonia Rating Scale, the Confusion Assessment Method Severity, the Montreal Cognitive Assessment, and the Overt Agitation Severity Scale. RESULTS: 24 individuals were analysed: 14 had positive NMDAR antibodies, and 10 had negative NMDAR antibodies in CSF. On admission, agitation/aggression, euphoria/exaltation, and disinhibition were more common in patients with positive antibodies. Excited catatonia and delirium were diagnosed more frequently in patients with positive antibodies. At discharge, there was an important decrease in neuropsychiatric symptoms, but substantial cognitive impairment remained. The mean hospitalisation length was 41.71 (SD 39.33) days for patients with definitive ANMDARE (p 0.259). CONCLUSIONS: Neuropsychiatric symptoms profile in ANMDARE was associated with the early onset of euphoria/exaltation and disinhibition, accompanied by marked psychomotor agitation. When ANMDARE was suspected, the presence of excited-type catatonia and delirium showed a tendency to predict definitive ANMDARE. At discharged, most patients recovered from catatonia, delirium, and psychosis, but marked cognitive symptoms, anxiety, and depression persisted at discharge.

FDG-PET in Cotard syndrome before and after treatment: can functional brain imaging support a two-factor hypothesis of nihilistic delusions?

Introduction: Cotard syndrome is a neuropsychiatric entity recognised by the presence of nihilistic delusions. Although different models have been proposed for the development of monothematic delusions, including Cotard syndrome, functional neuroanatomical models are lacking.Methods: A case report of a 19-year old male with autoimmune encephalitis and Cotard syndrome, in whom Positron Emission Tomography (18F-FDG-PET) scans were performed before and after successful treatment with electroconvulsive therapy (ECT), is presented. Literature review on brain imaging is provided to discuss a functional neuroanatomical model of Cotard syndrome, in accordance with the two-factor theory of delusions.Results: The patient's 18F-FDG-PET showed marked insular and prefrontal metabolic abnormalities. Except for insular hypometabolism, metabolic abnormalities improved after ECT. Previously reported structural neuroimaging studies in Cotard syndrome showed a predominance of right hemisphere lesions, in which frontal lobes were more frequently involved, followed by parietal and temporal lesions. Functional neuroimaging studies reported abnormalities in frontoparietal circuits as well as midline structures included in the "default mode network".Conclusions: Abnormalities in the functioning of the insular cortex and the prefrontal cortex could be related to the development of nihilistic delusions when a two-factor theory of delusions is considered.

Catatonia in patients with anti-NMDA receptor encephalitis.

AIM: There is a lack of studies related to the frequency, phenomenology, and associated features of catatonic syndrome in patients with anti-NMDA receptor encephalitis (ANMDARE). This study aimed to measure the frequency of catatonia in this condition and to delineate its particular symptoms. METHODS: A prospective study was done with all inpatients who fulfilled the criteria of definite ANMDARE admitted to the National Institute of Neurology and Neurosurgery of Mexico from January 2014 to September 2018. The Bush-Francis Catatonia Rating Scale and Braünig Catatonia Rating Scale were administered at admission. RESULTS: Fifty-eight patients were included and catatonia was diagnosed in 41 of these patients (70.6%). Immobility, staring, mutism, and posturing were the most frequent catatonic signs. Catatonia was associated with delirium, hallucinations, psychomotor agitation, generalized electroencephalography dysfunction, and previous use of antipsychotics. Mortality was present in 10% of the total sample; it was associated with status epilepticus, and was less frequent in the catatonia group. After immunotherapy, all cases showed a complete recovery from catatonic signs. CONCLUSION: This systematic assessment of catatonic syndrome shows that it is a frequent feature in patients with ANMDARE as part of a clinical pattern that includes delirium, psychomotor agitation, and hallucinations. The lack of recognition of this pattern may be a source of diagnostic and therapeutic errors, as most physicians associate catatonia with schizophrenia and affective disorders.

Catatonia in Neurologic and Psychiatric Patients at a Tertiary Neurological Center.

This study describes the prevalence, phenomenology, treatment, and outcome of neurological patients and psychiatric patients with catatonia at a tertiary neurological center. Clinical variables included nosological diagnoses and complications. Admission length and days with catatonia were used as outcome measures. Of 2,044 patients who were evaluated prospectively, 68 (3.32%) had catatonia, 42 (61.7%) were neurological patients, 19 (27.9%) were psychiatric patients, and 7 (10.2%) had drug-related diagnoses. Of all patients, the ratio of neurological to psychiatric patients was 3:1. Encephalitis was the most common diagnosis (N=26 [38.2%]), followed by schizophrenia (N=12 [17.6%]). Psychiatric patients exhibited a stuporous type of catatonia (15 [83.3%] versus 14 [33.3%], p>0.001), whereas neurological patients exhibited a mixed form of catatonia (25 [59.5%] versus 1 [5.6], p<0.001). Neurological patients had more complications, longer hospitalizations, and more days with catatonia. A total of 56 patients (82.3%) received lorazepam, and 14 patients (20.5%) underwent ECT. Second- and third-line treatments included amantadine, bromocriptine, and levodopa. Catatonia is a prevalent syndrome that can remit with proper and opportune treatment.

[Domestic violence in patients and caregivers dyads in neurological diseases]. / Violencia doméstica en díadas paciente-cuidador de enfermedades neurológicas.

INTRODUCTION: Patients with neurological diseases are susceptible to abuse and neglect. Studies on violence in this context have mainly focused on abuse perpetrated by a caregiver to the patient directionally. In this study we describe violence in dyads of caregivers and patients with neurological disorders according to frequency, directionality, and type of relation. METHODS: One-hundred-and-eighty-five caregiver-patient dyads were assessed by means of the National Survey of Violence Against Women (NSVAW) guidelines and the Zarit and Pfeiffer questionnaires. Bivariate analysis and Spearman correlation tests were performed. RESULTS: Violence was reported by 32.5% of caregivers and 33.5% of patients. In both groups, psychological abuse was the most common. Mutual violence (54.5%) is the most common type of abuse and the caregiver reported as having more violent behavior is the intimate partner. Epilepsy was the neurological disorder where violence was more prevalent (47.6%). CONCLUSIONS: The prevalence of violence in our sample is higher than the one for the general population of 21%, as reported by the NSVAW. Clinical neurologists and healthcare services are key elements for the detection of abuse in this context.

Stigma experience of people with epilepsy in Mexico and views of health care providers.

Epilepsy is a neurological disorder with neurobiological, cognitive, psychological, and social consequences. Epilepsy stigma is a social determinant of ill health that affects the quality of life of people who suffer from epilepsy and that renders a poor social prognosis even worse than the clinical one. From a phenomenological approach, between January and July 2011, we explored the experience of epilepsy stigma through 25 in-depth qualitative interviews with 10 persons with temporal lobe epilepsy (PWE) (we avoided terms such as "epileptics" or "epileptic patients" because they can be labeling and stigmatizing), 10 carers (CEs) of PWE who attended the epilepsy clinic of the Institute of Neurology and Neurosurgery of Mexico, and 5 physicians specialized in epilepsy. The objective of the study was to identify the following: perceptions that could indicate any form of discrimination due to having epilepsy, reactions of people in front of a person having seizures, and social functioning of PWE since epilepsy onset, particularly their interpersonal relationships and participation in educational or working activities. Through the health providers' narratives, we explored the mainstream care practices, their perspectives on epilepsy, and their views about how the disease should be addressed. Thematic guidelines were elaborated for each type of participant. All information was processed with the use of the computer-assisted data analysis, Atlas.ti5. We made a codification of broad themes that corresponded to the main topics of the interview guidelines and then proceeded to finer categorization to elaborate the analytical categories. Epilepsy was attached to a powerful stereotype that includes notions of contamination, danger, sin, divine punishment, supernatural forces, and madness. Internalized, interpersonal, and institutional stigma prevents PWE from participating in school and employment and reduces their opportunities to establish peer and couple relationships. Mexican's overt impunity of structural discrimination towards PWE shows a lack of available legal resources that protect their human rights. The narrow biomedical concept that physicians have of epilepsy is consistent with the limited medical practices that are offered to treat epilepsy at the health services in Mexico. Comprehensive treatment and integrated services for epilepsy must incorporate psychosocial programs that include epilepsy stigma as a major component of the disease.

Examining the Features of Neuroleptic Malignant Syndrome in Anti-NMDA Receptor Encephalitis: A Case-Control Study.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE) is a neuroimmunological disorder that frequently improves with immunotherapy. Symptomatic treatment with antipsychotics is common in the early stages when psychiatric symptoms predominate, and their use has been associated with serious side effects including neuroleptic malignant syndrome (NMS). The observation of an adverse response to antipsychotics, raising the suspicion of NMS, has been included as a criterion for possible autoimmune psychosis. METHODS: This case-control study included patients who received antipsychotics before referral to the National Institute of Neurology and Neurosurgery of Mexico, where they were diagnosed as having definite ANMDARE, and patients with ANMDARE who did not receive antipsychotics before referral. The neurologic and systemic features that are used to measure an adverse response to antipsychotics, raising the suspicion of NMS, were measured in both groups, including akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, and hyperthermia. A logistic regression analysis was used to determine the relationship between the previous use of antipsychotics and the occurrence of NMS-like reactions. RESULTS: A total sample of 112 patients with definite ANMDARE were included in the study. Fifty patients received antipsychotics before being referred to our institution. In this group, thirty-six patients (72%) were initially classified as having an adverse response, raising the suspicion of NMS, with the following features: akinesia (64%), autonomic instability (58%), generalized rigidity (52%), elevated concentrations of creatine phosphokinase (50%), and hyperthermia (14%). Six patients fulfilled the criteria for NMS (12%). The comparison with patients who did not receive antipsychotics before the clinical assessment did not show a significant difference between groups regarding the frequency of akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, or hyperthermia. Among different antipsychotics, only haloperidol was significantly associated with generalized rigidity as compared to patients who did not receive antipsychotics. CONCLUSIONS: Our study supports previous observations about the high frequency of autonomic dysfunction, hyperthermia, tachycardia, rigidity, and elevated creatine phosphokinase levels in patients with anti-NMDAR encephalitis following the administration of antipsychotic medications. Nevertheless, our study does not suggest a causal link between atypical antipsychotics and the onset of these neurological symptoms, as they were equally frequent among the group of patients who did not receive antipsychotic treatment.

Intimate Partner Violence in Persons With Parkinson's Disease.

Recent studies have reported that older adults with cognitive or physical disabilities are at risk to suffer intimate partner violence. This article investigates the intimate partner violence among caregivers and persons with Parkinson's disease (PD). We used qualitative methods to investigate whether the presence of violence was related to the type of couple relationship before the disease onset. We used a survey, in-depth interviews, and focus groups in 20 dyads of caregivers and patients. Twelve (60%) persons with PD and nine (45%) caregivers reported receiving violence. Considering their relationships previous to disease onset, we describe three typologies of violence in PD: (a) disease and history of violence, (b) disease as a buffer of violence, and (c) the burden of disease as an inductor of violence. Previous relationships and the couple's biographical trajectories influence the types of violence and its nature. This study is relevant as it considers time as a crucial factor in both the violence and suffering of PD and its caregiving.

Westphal variant Huntington disease and refractory catatonia: a case report.

A young woman with Westphal variant (juvenile) Huntington disease (HD) also developed catatonia. Catatonia is an underdiagnosed psychomotor syndrome often associated with neurological and psychiatric disorders, but it has rarely been documented in patients with HD. Catatonia usually responds to standard treatment with benzodiazepines and electroconvulsive therapy; however, this patient's catatonic syndrome did not improve until we augmented the standard treatment with amantadine and levodopa. The underlying pathophysiology and a neurochemical hypothesis of HD and catatonia can explain their comorbidity and the refractoriness of catatonia to treatment. Both conditions are linked to dysregulation of neurotransmitters in the striatocortical and corticocortical pathways. This understanding may serve as a guide for the use of nonstandard treatments. Our evidence also suggests that electroconvulsive therapy can be useful and safe in the treatment of HD.

[Neuropsychiatric aspects of anti-NMDA receptor encephalitis]. / Aspectos neuropsiquiátricos de la encefalitis por anticuerpos contra el receptor NMDA.

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.

[Autoinmune psychosis]. / Psicosis autoinmune.

With the advent of the description of autoimmune encephalitis by different neuronal cell-surface antibodies (anti-NMDAr, among others) and that psychosis may be the only manifestation without neurological symptoms (epilepsy, movement disorders, autonomic dysfunction, altered state of consciousness) in 6.5 % of patients, the term "autoimmune psychosis" has become remarkably interesting among researchers. In 2020, an international consensus for the description and diagnostic approach of autoimmune psychosis was created. Through this consensus, by taking different criteria into account, the definition of autoimmune psychosis was proposed at different degrees of certainty (possible, probable, and defined). The purpose of these criteria is to underpin the autoimmune origin in patients who present psychosis with atypical characteristics, thus justifying the realization of laboratory studies and complementary clinical tests (lumbar puncture, electroencephalogram, and magnetic resonance imaging of the brain); in addition, these criteria are applied in patients with psychosis without neurological symptoms that do not fully meet the criteria of autoimmune encephalitis. As in autoimmune encephalitis, the early initiation of immunotherapy has a direct impact on the functional prognosis of patients, so an early initiation of treatment must be considered in clinical scenarios of probable or definite autoimmune psychosis.

Con el advenimiento de la descripción de las encefalitis autoinmunes por diferentes anticuerpos neuronales de superficie (anti-NMDAr, entre otros) y que la psicosis puede ser la única manifestación sin síntomas neurológicos (epilepsia, alteraciones del movimiento, disautonomías, alteración del despierto) en 6.5 % de los pacientes, el término psicosis autoinmune ha retomado gran interés entre los investigadores. En 2020 se creó un consenso internacional para la descripción del término "psicosis autoinmune" y su abordaje diagnóstico. A través de este consenso, considerando diferentes criterios, se propone la definición de psicosis autoinmune en diferentes grados de certeza (posible, probable y definida). La finalidad de estos criterios es sustentar el origen autoinmune en pacientes que presenta psicosis con características atípicas, justificando así la realización de estudios de laboratorio y gabinete complementarios (punción lumbar, electroencefalograma, imagen de resonancia magnética de encéfalo); además, estos criterios se aplican a pacientes con psicosis sin síntomas neurológicos que no cumplen completamente con los criterios de encefalitis autoinmune. El inicio temprano de la inmunoterapia impacta directamente en el pronóstico funcional de los pacientes; se debe considerar el inicio temprano de tratamiento en cuadros clínicos de psicosis autoinmune probable o definida.

Brain MRI volumetric changes in the follow-up of patients with anti-NMDAr encephalitis.

INTRODUCTION: Autoimmune anti-NMDAr encephalitis is an antibody-mediated disorder characterized by psychiatric symptoms followed by decreased consciousness, dysautonomia and seizures. The pathophysiology of the disease is related to the internalization of NR1 subtype NMDA receptors and the dysfunction of structures where they are abundant (frontotemporal and insular regions). Some reports suggest the existence of cerebral atrophy in the follow-up of these patients, with conflicting evidence regarding its presence and usefulness as a marker of prognosis. METHODS: In a longitudinal, observational study, all patients with the diagnosis of definite anti-NMDAr autoimmune encephalitis with initial and control MRI studies were included. Conventional MR Brain acquisition was performed using a 3-Tesla Skyra MRI System. Automated brain segmental analysis was performed using the Volbrain volumetry system. The differences between baseline MRI volumetric characteristics and volumetric measures at follow-up was assessed. RESULTS: 25 patients were included (mean age 26.6, SD 9.6). 44% were females. The mean time between the studies was 24 (SD 21.4, 3-24) months. Significant volume loss was identified in the total brain volume (- 0.02%, p = 0.029), cerebellar volume (- 0.27%, p = 0.048) and brainstem volume (- 0.16%, p = 0.021). CONCLUSIONS: This study supports previous observations regarding volume loss in several brain regions of patients with antiNMDAr encephalitis. Further analyses are required to understand the role of treatment and severe clinical forms, as well as the relationship between volume loss and functional outcome.

Cotard syndrome in neurological and psychiatric patients.

The authors describe the frequency and characteristics of Cotard syndrome among neurological and psychiatric inpatients at a tertiary referral center. All inpatients from the National Institute of Neurology of Mexico (March 2007-May 2009) requiring neuropsychiatric consultation were reviewed. Among 1,321 inpatient consultations, 63.7% had neurological disease and one (0.11%) had viral encephalitis and Cotard syndrome. Of inpatients, 36.2% had pure psychiatric disorders and three (0.62%) had Cotard syndrome, associated with psychotic depression, depersonalization, and penile retraction (koro syndrome). This review discusses potential mechanisms for Cotard syndrome, including the role of a perceptual-emotional dissociation in self-misattribution in the deliré des negations.