Immunopsychiatry: an update on autoimmune encephalitis for neuropsychiatrists.

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.

Are Nutritional Patterns among Polish Hashimoto Thyroiditis Patients Differentiated Internally and Related to Ailments and Other Diseases?

There is not any diet recommended for Hashimoto's disease, despite that those patients are often undernourished. Because of the high heterogeneity of Hashimoto's patients, insight into dietary patterns might shed some light on the patient-tailored dietary approach, thus improving their treatment and helping to identify patients with the highest probability of particular nutritional deficiencies. The aim of this study was to identify Hashimoto's patients' dietary patterns and their characterization based on both socio-demographic variables and dietary self-assessment. We collected data online from patients with Hashimoto's disease. The questionnaire formula used in the study was developed based on a validated food frequency questionnaire KomPAN®. K-means pattern analyses were used to characterize patients into patterns based on the frequency of particular types of foods consumption and socio-demographic factors. Four patterns were identified. We labeled them as 'Convenient', 'Non-meat', 'Pro-healthy', and 'Carnivores' with participants proportions at approximately one-fourth per each pattern. The patients were mainly of the female gender (94.08%), with a female: male ratio of 15.9. Hashimoto's patients differed in their food product choices, food choice motives, dieting experience, nutritional knowledge, smoking habits, food allergies and intolerances, and lipid disorders, and thus represent different eating patterns. However, these patterns were not determined by comorbidities or the majority of ailments.

Psychiatric Phenotypes of Pediatric Patients With Seropositive Autoimmune Encephalitis.

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.

Psychiatric autoimmune conditions in children and adolescents: Is catatonia a severity marker?

OBJECTIVES: Patients with autoimmune encephalitis (AE) are likely to exhibit an acute onset of severe psychiatric features, including psychosis and/or catatonia. Based on the high prevalence of catatonia in AE and our clinical experience, we hypothesized that catatonia might be a marker of severity requiring more aggressive treatment approaches. METHODS: To reach a sufficient number of cases with brain-autoimmune conditions, we pooled two samples (N = 58): the first from the French National Network of Rare Psychiatric diseases and the second from the largest Italian neuro-pediatrics center for encephalopathies. Autoimmune conditions were diagnosed using a multidisciplinary approach and numerous paraclinical investigations. We retrospectively compared patients with and without catatonia for psychiatric and non-psychiatric clinical features, biological and imaging assessments, type of immunotherapy used and outcomes. RESULTS: The sample included 25 patients (43%) with catatonia and 33 (57%) without catatonia. Forty-two patients (72.4%) had a definite AE (including 27 anti-NMDA receptor encephalitis) and 16 (27.6%) suspected autoimmune encephalitis. Patients with catatonia showed significantly more psychotic features [18 (72%) vs 9 (27.3%), p < 0.001)] and more movement disorders [25 (100%) vs 20 (60.6%), p < 0.001] than patients without catatonia. First line (corticoids, immunoglobulin and plasma exchanges) and second line (e.g., rituximab) therapies were more effective in patients with catatonia, with 24 (96%) vs 22 (66.7%) (p = 0.006) and 17 (68%) vs 9 (27.3%) (p = 0.002), respectively. However, those with catatonia received more combinations of first and second line treatments and had more relapses during outcomes. CONCLUSION: Despite its exploratory design, the study supports the idea that autoimmune catatonia may be a marker of severity and morbidity in terms of initial presentation and relapses, requiring the need for early and aggressive treatment.

[Neuropsychopathology of autoimmune encephalitis with anti-NMDA receptor antibodies]. / Neuropsychopathologie de l'encéphalite auto-immune à anticorps anti-récepteurs NMDA.

Autoimmune encephalitis with anti-N-methyl-D-aspartate receptor antibodies is a neuropsychiatric disorder, with a psychopathological aspect in its early evolutionary phases, which often leads to psychiatric hospitalizations. This pathology is usually curable without sequelae. Its prognosis depends on the early diagnosis and therapeutic management. It is therefore important to mention this disorder when faced with any sudden neuropsychiatric presentation, especially if it is somewhat atypical and the subject is young.

The neuropsychological spectrum of anti-LGI1 antibody mediated autoimmune encephalitis.

Anti-Leucine Glioma Inactivated 1 (LGI-1) autoimmune encephalitis (AE) is a rare neuroinflammatory brain condition. Individuals afflicted with this condition can present with cognitive and psychological manifestations that can impact the individual's quality of life, day to day functioning, independence, return to work and interpersonal relationships. Our knowledge of the cognitive profiles and disease associated psychopathology is severely lacking. This review provides a comprehensive summary of the currently available literature, conceptualising our current understanding of the neuropsychological manifestations of anti LGI-1 AE and summarises methodological limitations of the current research to inform and improve future investigations. Key Terms: Autoimmune Diseases; Neuroimmunology; Autoimmune Encephalitis, Limbic Encephalitis; Anti-LGI1 Encephalitis, LGI1; Neuropsychology, Cognitive Assessment.

Thyroid gland and brain: Enigma of Hashimoto's encephalopathy.

The versatile clinical manifestations of the Hashimoto's chronic autoimmune thyroiditis often include psycho-neurological disorders. Although hypothyroidism disturbs significantly the ontogenesis and functions of central nervous system, causing in severe cases of myxedema profound impairment of cognitive abilities and even psychosis, the behavioral, motor and other psychoneurological disorders accompany euthyroid and slightly hypothyroid cases and periods of Hashimoto's disease as well, thus constituting the picture of so called "Hashimoto's encephalopathy". The entity, although discussed and explored for more than 50 years since its initial descriptions, remains an enigma of thyroidology and psychiatry, because its etiology and pathogenesis are obscure. The paper describes the development of current views on the role of thyroid in ontogeny and functions of brain, as well as classical and newest ideas on the etiology and pathogenesis of Hashimot's encephalopathy. The synopsis of the world case reports and research literature on this disorder is added with authors' own results obtained by study of 17 cases of Hashimoto's thyroiditis with schizophrenia-like clinical manifestations. The relation of the disease to adjuvant-like etiological factors is discussed. Three major mechanistic concepts of Hashimoto's encephalopathy are detailed, namely cerebral vasculitis theory, hormone dysregulation theory and concept, explaining the disease via direct action of the autoantibodies against various thyroid (thyroperoxidase, thyroglobulin, and TSH-receptor) and several extrathyroid antigens (alpha-enolase and other enzymes, gangliosides and MOG-protein, onconeuronal antigens) - all of them expressed in the brain. The article demonstrates that all above mentioned concepts intermingle and prone to unification, suggesting the unified scheme of pathogenesis for the Hashimoto's encephalopathy. The clinical manifestations, criteria, forms, course, treatment and prognosis of Hashimoto's encephalopathy and its comorbidity to other diseases - are also discussed in brief. The relation between Hashimoto's encephalopathy and non-vasculitis autoimmune encephalomyelitides of paraneoplastic and non-paraneoplastic origin is emphasized [1 figure, bibliography - 200 references].

Psychiatric manifestations and psychopharmacology of autoimmune encephalitis: A multidisciplinary approach.

The clinical presentations of autoimmune encephalitides tend to be a mixture of neuropsychiatric and somatic symptoms. The focus of this chapter concerns these clinical problems: the clinical phenomenology, the prevalence, and the possible pathophysiologies of anti-NMDAR or the other types of autoimmune encephalitis. We also specifically address the psychopharmacologic and nonpsychopharmacologic treatments. Our main questions are: What are the most used and best justified drug treatments? What are the most frequent side effects? And which other treatment options, such as ECT, are available? We discuss the main findings, present limitations, and we conclude by giving recommendations and presenting two algorithms.

Stress-induced hashitoxicosis: case report and relative HLA serotype and genotype

SUMMARY OBJECTIVE Even though stress has been long known as a provocative factor for Graves' disease, its relationship with Hashimoto's thyroiditis is more controversial. Studies on this topic are scanty. This paper aims to report a case of stress-induced Hashitoxicosis. RESULTS Here we report a case of Hashitoxicosis induced by a psychological stressful event in a 28-year-old woman with Hashimoto's thyroiditis. She had remained stably euthyroid for 12 years. She was first observed in April 2016, while euthyroid. She came back after 11 months because of fatigue and palpitations, in the absence of neck pain. Thyroid function tests revealed moderate thyrotoxicosis (undetectable TSH; FT4 36.94 pmol/L, normal values 9.0-24.46; FT3 13.50 pmol/L, normal values 3.07-6.14) with negative TSH-receptor antibodies. In the previous three months, she had experienced a psychological stressful event. Inflammatory markers were negative, and the white cell count was normal. Thyroid ultrasound revealed a modest increase in vascularization. Transient subclinical hypothyroidism ensued after seven weeks and spontaneously recovered. On the last visit, the patient was still on euthyroidism. (TSH 1.01 mU/L; FT4 9.22 pmol/L; FT3 3.98 pmol/L). We also performed HLA serotyping and genotyping. CONCLUSION This case demonstrates that, similarly to Graves' disease, Hashitoxicosis can also be triggered by stressful life events.

RESUMO OBJETIVO Mesmo que o estresse seja conhecido há muito tempo como um fator provocativo para a doença de Graves, sua relação com a tireoidite de Hashimoto é mais controversa. Estudos sobre esse tema são escassos. O objetivo deste artigo é relatar um caso de Hashitoxicose induzida por estresse. RESULTADOS Aqui nós relatamos um caso de Hashitoxicose induzido por um evento psicológico estressante em uma mulher de 28 anos com tireoidite de Hashimoto. Ela permaneceu estável eutireoidiana por 12 anos. Ela veio a nossa observação pela primeira vez em abril de 2016, enquanto eutireoidiana. Voltou após 11 meses por causa de fadiga e palpitações, na ausência de dor no pescoço. Testes de função tireoidiana revelaram uma tireotoxicose moderada (TSH indetectável; T4F 36,94 pmol/L, valores normais 9,0-24,46; FT3 13,50 pmol/L, valores normais 3,07-6,14) com anticorpos negativos para o receptor de TSH. Nos últimos três meses ela experimentou um evento psicológico estressante. Os marcadores inflamatórios foram negativos e a contagem de leucócitos foi normal. A ultrassonografia da tireoide revelou um aumento modesto da vascularização. Hipotireoidismo subclínico transitório ocorreu após sete semanas e se recuperou espontaneamente. Na última visita, a paciente ainda estava em eutireoidismo. (TSH 1,01 mU/L; FT4 9,22 pmol/L; FT3 3,98 pmol/L). Também realizamos a sorotipagem e a genotipização do HLA. CONCLUSÃO Este caso demonstra que, similarmente à doença de Graves, também a Hashitoxicose pode ser desencadeada por eventos estressantes da vida.

Calidad de vida en pacientes con hipotiroidismo / Quality of life in patients with Hypothyroidism

Introduction: Patients with hypothyroidism may have worse quality of life, specially in Hashimoto's Thyroiditis (HT). Objective: Describe differences in the quality of life in patients with HT, compared to other causes of hypothyroidism in ambulatory patients. Method: Cross sectional, observational and descriptive study. The survey SF36 was applied, with prior authorization, to hypothyroid outpatients over 18 years without psychiatric, physical or mental disorder, dividing the sample into two groups: patients with TH and other causes of hypothyroidism. We used QualityMetric Health OutcomesTM Scoring Software 5.0, that gives a descriptive analysis of each area included in the instrument. Results: 53 patients, of whom 30 where diagnosed with TH, and 23 with other causes of hypothyroidism were surveyed. The characteristics were similar in both groups. The total group of hypothyroid patients had mental component under the average. In the specific analysis of the groups, the physical component was within the average general population. The mental component, was decreased in patients with other causes of hypothyroidism, but not in patients with TH. Conclusion: Comparing both groups, there were no differences in the physical component of patients with hypothyroidism. The mental component of the total group of hypothyroid patients compared to the general population was below average, especially in patients with other causes of hypothyroidism. The reason is unclear, but could be related to the absence of endogenous thyroid hormones

Six autoantibodies associated with autoimmune encephalitis are not detectable in the cerebrospinal fluid of suicide attempters.

Previous findings suggest a link between neuroinflammatory processes and suicidality. Despite several lines of evidence supporting this link, including increased pro-inflammatory markers in blood-, cerebrospinal fluid (CSF)- and in post-mortem brain samples from suicidal individuals, the underlying mechanisms remain poorly understood. In this pilot study, we explored the possibility that autoimmune encephalopathies might be found among suicide attempters. We analysed the presence of six different autoantibodies (N-methyl-D-aspartate receptor, the α-amino-3-hydroxy-5-methyl-4-isoxazol-propionic acid receptor, the γ-amino-butyric acid B-receptor, the leucine-rich, glioma-inactivated 1, the contactin-associated protein-like 2, and the dipeptidyl-peptidase-like protein-6), all previously associated with psychopathology, in CSF samples from 29 unmedicated suicide attempters. Five of these subjects had high CSF/serum albumin ratio, indicative of increased blood-brain-barrier permeability. We were not able to detect any of these autoantibodies in the CSF samples. These pilot data do not support a role for autoimmune encephalopathies in suicidal behaviour, although the presence of lower levels of these autoantibodies cannot be ruled out in these patients.

Hashimoto's encephalopathy mimicking Creutzfeldt-Jakob disease.

Hashimoto's encephalopathy is a rare, imprecisely defined autoimmune neurologic syndrome associated with Hashimoto's thyroiditis that normally responds to corticosteroids. Here, we describe the case of a 55-year-old woman who presented with subacute cognitive decline and ataxia. Neoplastic, paraneoplastic, infectious, and metabolic etiologies were ruled out. Anti-TPO antibody level was markedly elevated at 966U/mL. After one month of 60mg/day of oral prednisone, she felt back to baseline and her Montreal Cognitive Assessment dramatically improved. Physicians should strongly consider this uncommon diagnosis in patients with rapid cognitive decline and no other clear etiology.

Attempted infanticide and suicide inaugurating catatonia associated with Hashimoto's encephalopathy: a case report.

BACKGROUND: Catatonia is a neuropsychiatric syndrome with motor and behavioural symptoms. Though usually occurring in patients with schizophrenia and mood disorders, this syndrome may also be associated with neurological diseases or general medical conditions. Few cases of catatonia associated with autoimmune disorders have been described. CASE PRESENTATION: Here, we report the case of a 27-year-old woman diagnosed with Hashimoto's encephalitis (HE) who attempted suicide and infanticide by defenestration. As she presented risk factors for postpartum psychosis, she was treated principally with antipsychotics. Despite adequate treatment for psychosis, symptoms worsened and she developed catatonia. Complementary investigations showed elevated titres of anti-thyroglobulin and anti-thyroperoxidase antibodies (200 and 10 times, respectively, as compared to normal levels) and electroencephalography were suggestive of encephalopathy. In the presence of an otherwise unexplained neuropsychiatric condition, HE was suspected and oral prednisolone was introduced. Psychiatric symptoms improved dramatically within 72 h and the patient was still free of any symptom 3 years later. CONCLUSION: Catatonia of organic aetiology should always be considered before a psychiatric aetiology especially in case of clinical worsening in spite of adequate psychotropic treatment. To our knowledge, this is the first description of catatonia associated with HE.

Sexual function and depressive symptoms in young women with thyroid autoimmunity and subclinical hypothyroidism.

OBJECTIVE: The results of few studies conducted to date suggest an increased prevalence of sexual dysfunction in patients with thyroid disorders. DESIGN: The aim of this study was to compare female sexual function and depressive symptoms between women with autoimmune thyroid disease and with mild thyroid failure. PATIENTS: The study included four groups of young women: euthyroid women with Hashimoto's thyroiditis (Group 1), women with nonautoimmune subclinical hypothyroidism (Group 2), women with autoimmune subclinical hypothyroidism (Group 3) and healthy euthyroid females without thyroid autoimmunity (Group 4). MEASUREMENTS: Beyond measuring serum hormone levels and thyroid antibody titres, all enrolled women completed questionnaires evaluating female sexual function (Female Sexual Function Index - FSFI) and the presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition - BDI-II). RESULTS: The mean total FSFI score was lower in women with autoimmune hypothyroidism than in the remaining groups of women, as well as lower in Groups 1 and 2 than in Group 4. Compared to Group 4, three domains (sexual desire, lubrication and sexual satisfaction) were lower in Group 1, four domains (desire, arousal, lubrication and dyspareunia) in Group 2 and all FSFI domain scores in Group 3. The total BDI-II score was higher in Groups 1 and 2 than in Group 4, as well as higher in Group 3 than in the other groups of women. CONCLUSIONS: The obtained results suggest that both thyroid autoimmunity and mild thyroid failure, particularly if they occur together, may negatively affect female sexual function and depressive symptoms.

Quality of life improvement in patients with Hashimoto thyroiditis and other goiters after surgery: A prospective cohort study.

INTRODUCTION: Hashimoto thyroiditis (HT) and other benign goiters (BG) might influence patients' quality of life (QoL). The objective of this study was to analyze influence of surgery on these patients' QoL. METHODS: A prospective cohort study was conducted. The ThyPRO questionnaire was used in the QoL assessment. RESULTS: The HT patients experienced significantly worse hypothyroid symptoms and sex life than the BG patients. The improvement in QoL in the BG patients was significant after surgery in all ThyPRO domains. In the HT patients, the improvement was significant in all but two domains, eye symptoms and cognitive impairment. The best improvement in both groups was in overall QoL. None of the patients developed permanent consequences. CONCLUSIONS: The QoL of HT and BG patients is impaired and improves significantly after surgical treatment. Thyroidectomy should be considered as a treatment option in the HT patients more often as in the BG patients.

Anti-Ma2-encephalitis in a 2 year-old child: A newly diagnosed case and literature review.

BACKGROUND: Anti-Ma2-associated encephalitis is a rare paraneoplastic neurological syndrome characterized by isolated or combined limbic, diencephalic, or brainstem dysfunction. It is rarely reported in children. CASE STUDY: We describe the clinical data of a 2-year-old girl referred to our department for refractory focal seizures associated with fever, followed by behavioural changes, speech disturbances and confusional episodes. Brain magnetic resonance imaging (MRI) showed left temporoparietal brain involvement. Haematological, biochemical and infectious evaluations were unremarkable. Autoimmune encephalitis was suspected. Paraneoplastic antibodies tests showed positive results for anti-Ma2 antibodies. Screening for underlying tumour was negative. Immunomodulatory treatment was administrated. The patient showed improvement of vigilance and behaviour. However, she kept refractory epilepsy. CONCLUSION: Although poor response to immunotherapy, early diagnosis and appropriate treatment of this disorder may prevent irreversible sequelae.

[The polyglandular autoimmune syndrome--quality of life and family clustering]. / Das polyglanduläre Autoimmunsyndrom--Lebensqualität und familiäre Beteiligung.

BACKGROUND AND AIM: For patients with polyglandular autoimmune syndrome (PGA), data pertaining to familial clustering and quality of life are missing. Therefore, we performed a prospective and controlled study to collect this information. PATIENTS AND METHODS: Clinical and serological evaluation of 75 consecutively recruited patients with PGA (mean age 47,5 ± 15,3 years; 65,3% women) and their 108 relatives (mean age 33,13 ± 20,08 years; 65,7% women) was performed. Three validated questionnaires for psychosocial evaluation (quality of life short form 36 [SF-36], hospital anxiety and depression scale [HADS] and the Gießener Beschwerdebogen [GBB]) were answered by patients and relatives. RESULTS: 47 (62%) patients with PGA had type 1 diabetes and autoimmune thyroid disease. 56 (52%) of their relatives had an autoimmune disease whereas Hashimoto's thyroiditis and type-A-gastritis were the most prevalent endocrine and non-endocrine components. Thyroid peroxidase autoantibodies were most prevalent in patients and involved relatives. Compared to a German reference group, all scales of the SF-36 were markedly decreased in patients and involved relatives (p < 0.001). Anxiety and depression scales were pathologically increased in patients and relatives (p < 0.001). Also, all GBB scales were elevated for patients and relatives (p < 0.001). Patients with both glandular and non-glandular autoimmune diseases showed the most pathological psychosocial results. CONCLUSION: Familial clustering is high in patients with PGA. Quality of life and psychosocial status are poor in patients and involved relatives. Multidisciplinary management of the multiplex families in specialized centers is warranted.

Cognitive and affective dysfunctions in autoimmune thyroiditis.

Hashimoto's thyroiditis (HT) is the most frequent cause of hypothyroidism in areas with sufficient iodine intake. While the impact of thyroid function on mood and cognition is well known, only in the recent years, an increasing number of studies report on the association of HT with cognitive and affective disturbances also in the euthyroid state. Recent imaging studies have shown that these impairments are accompanied by altered brain perfusion, in particular, in the frontal lobe and a reduced gray matter density in the left inferior gyrus frontalis. Brain function abnormalities in euthyroid patients with HT may be subtle and only detected by specific testing or even severe as it is the case in the rare neuropsychiatric disorder Hashimoto's encephalopathy (HE). The good response to glucocorticoids in patients with HE indicates an autoimmune origin. In line with this, the cognitive deficits and the high psycho-social burden in euthyroid HT patients without apparent signs of encephalopathy appear to be associated with anti-thyroid peroxidase auto-antibody (TPO Abs) levels. Though in vitro studies showing binding of TPO Abs to human cerebellar astrocytes point to a potential direct role of TPO Abs in the pathogenesis of brain abnormalities in HT patients, TPO Abs may function only as a marker of an autoimmune disorder of the central nervous system. In line with this, anti-central nervous system auto-antibodies (CNS Abs) which are markedly increased in patients with HT disturb myelinogenesis in vitro and, therefore, may impair myelin sheath integrity. In addition, in HT patients, production of monocyte- and T-lymphocyte-derived cytokines is also markedly increased which may negatively affect multiple neurotransmitters and, consequently, diverse brain neurocircuits.