Cardiopulmonary Coupling Spectrogram as an Ambulatory Method for Assessing Sleep Disorders in Patients With Autoimmune Encephalitis.

BACKGROUND AND OBJECTIVES: Sleep disorders are a common and important clinical feature in patients with autoimmune encephalitis (AE); however, they are poorly understood. We aimed to evaluate whether cardiopulmonary coupling (CPC), an electrocardiogram-based portable sleep monitoring technology, can be used to assess sleep disorders in patients with AE. METHODS: Patients fulfilling the diagnostic criteria of AE were age- and sex-matched with recruited healthy control subjects. All patients and subjects received CPC testing between August 2020 and December 2022. Demographic data, clinical information, and Pittsburgh Sleep Quality Index (PSQI) scores were collected from the medical records. Data analysis was performed using R language programming software. RESULTS: There were 60 patients with AE (age 26.0 [19.8-37.5] years, male 55%) and 66 healthy control subjects (age 30.0 [25.8-32.0] years, male 53%) included in this study. Compared with healthy subjects, patients with AE had higher PSQI scores (7.00 [6.00-8.00] vs 3.00 [2.00-4.00], p < 0.001), lower sleep efficiency (SE 80% [71%-87%] vs 92% [84%-95%], p < 0.001), lower percentage of high-frequency coupling (25% [14%-43%] vs 45% [38%-53%], p < 0.001), higher percentage of REM sleep (19% ± 9% vs 15% ± 7%, p < 0.001), higher percentage of wakefulness (W% 16% [11%-25%] vs 8% [5%-16%], p = 0.074), higher low-frequency to high-frequency ratio (LF/HF 1.29 [0.82-2.40] vs 0.91 [0.67-1.29], p = 0.001), and a higher CPC-derived respiratory disturbance index (9.78 [0.50-22.2] vs 2.95 [0.40-6.53], p < 0.001). Follow-up evaluation of 14 patients showed a decrease in the PSQI score (8.00 [6.00-9.00] vs 6.00 [5.00-7.00], p = 0.008), an increased SE (79% [69%-86%] vs 89% [76%-91%], p = 0.030), and a decreased W% (20% [11%-30%] vs 11% [8%-24], p = 0.035). Multiple linear regression indicated that SE (-7.49 [-9.77 to -5.21], p < 0.001) and LF/HF ratio (0.37 [0.13-0.6], p = 0.004) were independent factors affecting PSQI scores in patients with AE. DISCUSSION: Sleep disorders with autonomic dysfunction are common in patients with AE. Improvements in the PSQI score and SE precede the restoration of sleep microstructural disruption in the remission stage. CPC parameters may be useful in predicting sleep disorders in patients with AE.

Sudden unexpected death in epilepsy and ictal asystole in patients with autoimmune encephalitis: a systematic review.

OBJECTIVE: As autoimmune encephalitis (AE) often involves the mesial temporal structures which are known to be involved in both sudden unexpected death in epilepsy (SUDEP) and ictal asystole (IA), it may represent a good model to study the physiopathology of these phenomena. Herein, we systematically reviewed the occurrence of SUDEP and IA in AE. METHODS: We searched 4 databases (MEDLINE, Scopus, Embase, and Web of Science) for studies published between database inception and December 20, 2022, according to the PRISMA guidelines. We selected articles reporting cases of definite/probable/possible/near-SUDEP or IA in patients with possible/definite AE, or with histopathological signs of AE. RESULTS: Of 230 records assessed, we included 11 cases: 7 SUDEP/near-SUDEP and 4 IA. All patients with IA were female. The median age at AE onset was 30 years (range: 15-65), and the median delay between AE onset and SUDEP was 11 months; 0.9 months for IA. All the patients presented new-onset seizures, and 10/11 also manifested psychiatric, cognitive, or amnesic disorders. In patients with SUDEP, 2/7 were antibody-positive (1 anti-LGI1, 1 anti-GABABR); all IA cases were antibody-positive (3 anti-NMDAR, 1 anti-GAD65). Six patients received steroid bolus, 3 intravenous immunoglobulin, and 3 plasmapheresis. A pacemaker was implanted in 3 patients with IA. The 6 survivors improved after treatment. DISCUSSION: SUDEP and IA can be linked to AE, suggesting a role of the limbic system in their pathogenesis. IA tends to manifest in female patients with temporal lobe seizures early in AE, highlighting the importance of early diagnosis and treatment.

How does Hashimoto's thyroiditis affect bone metabolism?

Bone marrow contains resident cellular components that are not only involved in bone maintenance but also regulate hematopoiesis and immune responses. The immune system and bone interact with each other, coined osteoimmunology. Hashimoto's thyroiditis (HT) is one of the most common chronic autoimmune diseases which is accompanied by lymphocytic infiltration. It shows elevating thyroid autoantibody levels at an early stage and progresses to thyroid dysfunction ultimately. Different effects exert on bone metabolism during different phases of HT. In this review, we summarized the mechanisms of the long-term effects of HT on bone and the relationship between thyroid autoimmunity and osteoimmunology. For patients with HT, the bone is affected not only by thyroid function and the value of TSH, but also by the setting of the autoimmune background. The autoimmune background implies a breakdown of the mechanisms that control self-reactive system, featuring abnormal immune activation and presence of autoantibodies. The etiology of thyroid autoimmunity and osteoimmunology is complex and involves a number of immune cells, cytokines and chemokines, which regulate the pathogenesis of HT and osteoporosis at the same time, and have potential to affect each other. In addition, vitamin D works as a potent immunomodulator to influence both thyroid immunity and osteoimmunology. We conclude that HT affects bone metabolism at least through endocrine and immune pathways.

Thyroiditis: Evaluation and Treatment.

Thyroiditis is a general term for inflammation of the thyroid gland. The most common forms of thyroiditis encountered by family physicians include Hashimoto, postpartum, and subacute. Most forms of thyroiditis result in a triphasic disease pattern of thyroid dysfunction. Patients will have an initial phase of hyperthyroidism (thyrotoxicosis) attributed to the release of preformed thyroid hormone from damaged thyroid cells. This is followed by hypothyroidism, when the thyroid stores are depleted, and then eventual restoration of normal thyroid function. Some patients may develop permanent hypothyroidism. Hashimoto thyroiditis is an autoimmune disorder that presents with or without signs or symptoms of hypothyroidism, often with a painless goiter, and is associated with elevated thyroid peroxidase antibodies. Patients with Hashimoto thyroiditis and overt hypothyroidism are generally treated with lifelong thyroid hormone therapy. Postpartum thyroiditis occurs within one year of delivery, miscarriage, or medical abortion. Subacute thyroiditis is a self-limited inflammatory disease characterized by anterior neck pain. Treatment of subacute thyroiditis should focus on symptoms. In the hyperthyroid phase, beta blockers can treat adrenergic symptoms. In the hypothyroid phase, treatment is generally not necessary but may be used in patients with signs and symptoms of hypothyroidism or permanent hypothyroidism. Nonsteroidal anti-inflammatory drugs and corticosteroids are indicated for the treatment of thyroid pain. Certain drugs may induce thyroiditis, such as amiodarone, immune checkpoint inhibitors, interleukin-2, interferon-alfa, lithium, and tyrosine kinase inhibitors. In all cases of thyroiditis, surveillance and clinical follow-up are recommended to monitor for changes in thyroid function.

Clinical Characteristics and Follow-Up of 19 Children With Hashimoto's Thyroiditis Aged Below 3 Years: A Single-Center Retrospective Analysis.

Aim: To analyze the clinical characteristics of Hashimoto's thyroiditis (HT) in children below 3 years of age in order to improve the understanding of the disease, avoid misdiagnosis, and achieve early diagnosis and treatment. Methods: The study retrospectively analyzed the clinical data of 19 patients diagnosed with HT in the first three years of life. Results: The patients (12 female, 7 male) had an average age of 26.1 ± 8.2 months (range 10-36 months). At presentation, one patient had euthyroidism, ten had hypothyroidism, seven had subclinical hypothyroidism, and one had hyperthyroidism. The most common reasons for doctor's visits were thyroid enlargement (21.1%), global developmental delay (21.1%), and routine thyroid function tests in patients with type 1 diabetes (26.3%). Sixteen patients provided follow-up data, and the mean follow-up time was 23.31 ± 16.44 months (range 1-48 months). In the hypothyroidism group, one patient stopped levothyroxine (LT4) treatment after 2 months; the remaining patients had been treated with LT4 since their diagnosis. In the subclinical hypothyroidism group, one patient whose thyroid function returned to normal after 1 month of being diagnosed was not treated. The remaining patients received LT4 treatment at their diagnosis or during follow-up. The patient with hyperthyroidism was treated with methimazole after diagnosis, but treatment was discontinued 11 months later and LT4 was initiated 26 months after diagnosis. One in four patients with global developmental delay approached normal mental development after LT4 treatment. Four in six patients with short stature achieved height catch-up. Conclusion: At their initial HT diagnosis, most of the children showed hypothyroidism or subclinical hypothyroidism. Children with global developmental delay require continual screening, even if the thyroid function is normal after birth, to determine whether they have HT-induced hypothyroidism. Thyroxine replacement could partially relieve the clinical manifestations of hypothyroidism and early diagnosis and treatment are essential for improving patient prognosis.

Body Composition and Serum Anti-Müllerian Hormone Levels in Euthyroid Caucasian Women With Hashimoto Thyroiditis.

Objective: Women with Hashimoto thyroiditis (HT) are characterized by increased incidence of infertility and disturbances in body composition. Serum anti-Müllerian hormone (AMH), which reflects functional ovarian reserve, is decreased in women with HT and it be related to body mass. The aim of the present study was to investigate the relation between serum levels of AMH and body composition in HT compared to control group. Patients and Methods: We examined 85 euthyroid women: 39 subjects with HT and 46 control women. Body composition was analysed by dual-energy X-ray absorptiometry and with bioimpedance method. Serum concentrations of AMH, leptin, TSH, thyroid hormones were assessed. Results: We observed lower serum concentration of AMH in women with HT in comparison to the control group (p=0.01), but without differences in serum concentration of leptin between studied groups (p=0.28). Women with HT were characterized by higher %body fat (p=0.01) estimated with bioimpedance method without differences in BMI, android and gynoid fat mass and visceral adipose tissue (VAT) mass estimated with DXA method when compared to the control group (all p>0.05). We found a negative relationship between serum concentration of AMH and %body fat (r=-0.38,p=0.03) in women with HT. Additionally, in HT group, the relationship between serum levels of AMH and leptin was not statistically significant (r=0.01,p=0.96). We observed a relationship between serum concentration of leptin and BMI, %body fat mass, android, gynoid and VAT mass in HT and in the control group (all p<0.01). Conclusions: Women with HT are characterized by lower levels of AMH and it is associated with higher fat mass, independently of serum levels of leptin.

Influence of thyroid hormone in the expression of the marker pro-apoptosis BID, in spite of the predominance of anti-apoptosis activation in intratiroidal lymphocytic infiltration in Hashimoto's thyroiditis.

Cell destruction in Hashimoto's thyroiditis (HT) involves autoantibodies and cytotoxic T lymphocytes. Thyrocytes maintenance occurs by pro-apoptotic, anti-apoptotic and cell proliferation balance. OBJECTIVES: To characterize factors related to the mechanisms of apoptosis and cell proliferation in thyroid cells and intrathyroid lymphocytic infiltrate in HT. METHODS: We assessed lymphocytic infiltrate and thyroid cells from HT and normal thyroid by immunohistochemical analysis of cell proliferation (Ki-67), antiproliferation (p27Kip1), pro-apoptosis (Fas, Fas-ligand, BID) and anti-apoptosis (MCL-1, BCL2) markers. RESULTS: Lymphocytic infiltrate presented BCL2 and MCL-1 higher expression, Ki-67 and p27kip1 balance. Thyrocytes exhibited Fas and FasL balance, higher BID expression; MCL-1, BCL-2, Ki-67 similar to the normal thyroid. T4 and higher lymphocytes BID expression were associated. CONCLUSIONS: In lymphocytic infiltrate predominated anti-apoptosis in relation to pro-apoptosis except for BID. Thyrocytes presented pro-apoptosis and anti-apoptosis balance and cell proliferation similar to normal thyroid. T4-associated BID expression in HT lymphocytes suggests the influence of thyroid hormone as a signal to up-regulate the BID pro-apoptotic protein and thus increase lymphocytic apoptosis rates.

Cytokine/Chemokine/Growth Factor Profiles Contribute to Understanding the Pathogenesis of the Salivary Gland Dysfunction in Euthyroid Hashimoto's Thyroiditis Patients.

Hashimoto's thyroiditis (HT) is one of the most common autoimmune diseases. It is suggested that, in addition to thyroid gland dysfunction, HT is responsible for impaired secretion from the salivary glands. The aim of this study was to evaluate the extent of symptoms of salivary gland dysfunction. We also assessed the relationship between the levels of selected cytokines, chemokines, and growth factors in unstimulated whole saliva (UWS) and the rate of UWS secretion and symptoms of xerostomia in HT patients. The study group consisted of 25 female patients diagnosed with Hashimoto's disease in its spontaneous euthyroid state who had never received hormonal treatment. In more than half of the examined patients, we observed the level of UWS secretion below 0.2 mL/min, indicating impaired secretory function of the salivary glands. Moreover, we demonstrated that the clinical symptoms of salivary gland dysfunction worsen with disease duration. Nevertheless, the inflammatory changes occurring in these glands are independent of general inflammation in the course of HT. Our results clearly indicate an abnormal profile of cytokines, chemokines, and growth factors in the UWS of HT euthyroid women as well as the fact that concentrations of IL-6 and IL-1 as well as INF-γ, TNF-α, and IL-12 may be potential biomarkers for salivary gland dysfunction in the course of HT. Furthermore, salivary IL-12 (p40) may be helpful in assessing the progression of autoimmunity-related inflammation in the course of HT. In conclusion, secretory dysfunction of the salivary glands is closely related to autoimmunity-related inflammation in the course of HT, which leads to objective and subjective symptoms of dry mouth.

Reversal of Abnormal CD4+ T Cell Metabolism Alleviates Thyroiditis by Deactivating the mTOR/HIF1a/Glycolysis Pathway.

Background: Hashimoto's thyroiditis (HT) is an autoimmune disease that features activation of thyroid antigen-specific helper T cells. HT patients have increased Th1 and Th17 T cell subsets. Glycolysis supports chronic activation of Th1 and Th17 T cells, but how this contributes to HT remains unknown. Methods: The metabolism of CD4+ T cells from 30 HT patients and 30 healthy controls was evaluated by determining the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR). Mice in a subacute thyroiditis (SAT) model were treated with 2DG, metformin, or combination. Metrics of mTOR/HIF-1α/HK2/glycolysis were measured by western blot and Seahorse assay methods. The severity of SAT was measured by flow cytometry and HE staining. Results: CD4+ T cells from HT patients had enhanced ECAR and OCR. Levels of Glut1, HK2, PKM2, and LDHA in cultured HT CD4+ T cells were elevated. The expression of HK2 and PKM2 in cultured SAT CD4+ T cells was elevated compared with the control group. Activation of the mTOR and HIF-1α pathways was significant in SAT mice, and expression of HIF-1α in the 2DG treated group was reduced. Treatment with 2DG and/or metformin significantly decreased the ratio of Th17 and Th1 T cells. Conclusions: Thyroiditis results in elevation of the mTOR/HIF-1α/HK2/glycolysis pathway in CD4+ T cells. The activation of this pathway is reduced by treatment with 2DG and metformin, which also reverted imbalances in CD4+ T cell differentiation.

Clinical, biochemical, and radiological follow-up results of children and adolescents with Hashimoto's thyroiditis: a single-center experience.

OBJECTIVES: Hashimoto's thyroiditis (HT) is the most common cause of goiter and acquired hypothyroidism in children and adolescents, especially in areas without endemic iodine deficiency. We aimed to evaluate the follow-up results of children and adolescents diagnosed with HT, including clinical, biochemical, and radiological findings and treatment approaches. METHODS: HT patients, who were diagnosed between 2012 and 2018 years in a single-center, were assessed retrospectively. RESULTS: Two hundred and twenty-four cases were included in the study, 75.9% of whom were girls (female/male ratio: 3.1) and 66.5% were pubertal. The median age of the cases at first admission was 12.5 (9.2-15) years. The median follow-up period of 196 patients, who continued their follow-up regularly, was 2.1 (0.7-4.8) years. When autoantibody levels were analyzed according to gender, mean anti-Tg levels were higher in girls (p=0.028), whereas anti-TPO levels were similar (p=0.372). A nodule was detected in the ultrasonographic follow-up of 29 (13%) patients. Papillary thyroid carcinoma was observed in 10.3% (n=3) of those with nodules. When the last ultrasonography findings of 188 patients with available radiological follow-up data were compared with their initial evaluation, the rate of heterogeneous parenchymal echogenicity increased significantly (p=0.008). The need for l-thyroxine dosage augmented over time. CONCLUSIONS: Although HT is more common in adolescent girls, it can be encountered in both genders and at all ages in childhood. The incidence of malignancy was not higher in patients with nodules associated with HT than the reported incidences of malignancy in nodules not associated with HT.

Assessment of Visual and Brainstem Auditory Evoked Potentials in Patients with Hashimoto's Thyroiditis.

BACKGROUND: The present study was aimed to evaluate parameters of visual and brainstem auditory evoked potentials (VEP, BAEP) in euthyreotic Hashimoto's thyroiditis (HT) patients without central nervous system involvement. METHODS: 100 HT patients (92 women, 8 men), mean age 46.9 years, and 50 healthy controls. They underwent a neurological examination, thyroid hormone levels, thyroid autoantibody titers, and brain imaging. Latencies and amplitudes of the N75, P100, and N145 component of VEP and the I-V components of BAEP were analyzed. RESULTS: The neurological examination revealed in 31 patients signs of increased neurovegetative excitability. Brain resonance imaging showed no abnormalities in HT patients. The mean P100, relative P100, and N145 VEP latencies were significantly longer, and P100 amplitude significantly higher in HT patients than the controls. HT patients also had a longer mean wave BAEP V latency and mean wave III-V and I-V interpeak latencies, and significantly lower mean wave I and V amplitudes. Abnormal VEP and BAEP were recorded in 34% of the patients. There were no statistically significant correlations between the mean VEP parameters and thyroid profile and the applied dose of L-thyroxine. There was a relationship between the level of TSH and the wave BAEP III-V interpeak latency. CONCLUSIONS: There were changes in the brain's bioelectrical activity in one-third of the patients with HT without nervous system involvement. The increased amplitude of the VEP may indicate increased cerebral cortex activity. Disorders of the brain's bioelectrical activity in the course of HT may be associated with an autoimmune process.

Immunomodulatory Function of Vitamin D and Its Role in Autoimmune Thyroid Disease.

Vitamin D is one of the most important nutrients required by the human body. It is a steroid hormone that plays an important role in regulating calcium and phosphorus metabolism, and bone health. Epidemiological studies have revealed a close correlation between vitamin D and many common chronic diseases. Additionally, vitamin D has recently been shown to act as an immunomodulatory hormone, and, accordingly, vitamin D deficiency was uncovered as a risk factor for autoimmune thyroid diseases, although the underlying mechanisms are still unknown. It is therefore necessary to disclose the role and mechanism of action of vitamin D in the occurrence and development of autoimmune thyroid diseases. This knowledge will help design intervention and early treatment strategies for patients with autoimmune thyroid diseases who present with low levels of vitamin D.

Seizures in autoimmune encephalitis-A systematic review and quantitative synthesis.

OBJECTIVE: This study aimed to evaluate the proportion of patients with seizures and electroencephalography (EEG) abnormalities in autoimmune encephalitis (AE) and its most common subtypes. METHODS: This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standards and was registered with the International Prospective Register of Systematic Reviews (PROSPERO). We searched Medline All, Embase, and PsychINFO in Ovid from inception to June 2019 for articles pertaining to AE and seizure. Included studies reported seizure and/or EEG data in cohorts of ≥10 AE patients. Patient demographics, antibody type, seizure incidence, and EEG findings were extracted. Review of studies and data extraction were performed in duplicate. In addition to descriptive analysis, quantitative synthesis stratified by autoantibody subtype was performed with logistic regression and chi-square analyses. RESULTS: Our search yielded 3856 abstracts: 1616 were selected for full-text review and 118 studies met eligibility criteria. Of 3722 antibody-positive AE patients, 2601 (69.9%) had clinical seizures during the course of their illness. Of the 2025 patients with antibody-positive AE and available EEG data, 1718 (84.8%) had some EEG abnormality (eg, epileptiform discharges, slowing, and so on). Anti- N-methyl-d-aspartate (NMDA) receptor encephalitis (anti-NMDARE) was the most commonly reported type of AE (1985/3722, 53.3%). Of the anti-NMDARE patients with available seizure or EEG data, 71.8% (n = 1425/1985) had clinical seizures during their illness, and 89.7% (n = 1172/1306) had EEG abnormalities. For all AE patients and in the anti-NMDARE subpopulation, seizures were more common in younger patients (p < .05). SIGNIFICANCE: This systematic review provides an estimate of the proportion of AE patients with seizures, confirming the magnitude of seizure burden in this population. Prospective studies are needed to understand population-based prevalence of seizures, identify factors associated with seizures, and evaluate particular EEG findings as biomarkers of seizures and outcomes in AE.

The evaluation of Hashimoto's thyroiditis with event-related potentials and magnetic resonance spectroscopy and its relation to cognitive function.

Thyroid dysfunction is very often accompanied by cognitive and affective disorders. The frequency of these disorders in patients with compensated Hashimoto's thyroiditis (HT) is unknown. The aim of the present study was to evaluate brain dysfunction in euthyroid HT patients by means of event-related potentials (ERP) and magnetic resonance spectroscopy (MRS) and to correlate it with cognitive function. 68 patients with HT (59 female, 9 male) and 45 healthy controls were included in the study. All the patients underwent ERP including an analysis of N200 and P300 response parameters. MRS voxels were located in the posterior cingulate gyrus (PCG) and the left parietal white matter (PWM). The NAA/Cr, mI/Cr, and Cho/Cr ratios were analysed. The ERP parameters, MRS metabolite ratios and hormonal concentrations (TSH, fT3, fT4) as well as TGAb and TPOAb titer were also correlated. There was a significant prolongation of the latencies of N200 and P300 potentials and a significant decrease of P300 amplitude in HT patients than in the control group. There was a significant positive correlation between the mI/Cr ratio in the PCG area and P300 latencies. NAA/Cr ratio in the PCG region showed significant negative correlations with all N200 latencies. The results may suggest brain dysfunction in neurologically asymptomatic HT patients. ERPs undergo significant changes in patients with HT and may, in combination with MRS, constitute an important element in the recognition and monitoring of cognitive functions in this group of patients.

Lateralized Rhythmic Delta Activity in Patients With Infectious or Autoimmune Insular Lesions.

INTRODUCTION: Lateralized rhythmic delta activity (LRDA) is a rare pattern on the ictal-interictal continuum (IIC) encountered in critically ill patients. Its association with acute seizures is yet to be fully explored. Insular involvement is a common finding in patients with infectious and autoimmune encephalitis. The association between acute insular lesions and the ictal-interictal continuum, particularly LRDA, has not been explored before. METHODS: A case series of 4 patients with either herpetic or autoimmune encephalitis and prominent insular cortex involvement who had LRDA when monitored on continuous EEG is being presented. RESULTS: Two patients had herpetic encephalitis and 2 patients had autoimmune encephalitis. All patients had either clinical or electrographic seizures with 1 patient progressing into new-onset refractory status epilepticus. CONCLUSION: LRDA can be seen in patients with insular cortex acute inflammation. In this group of patients, LRDA may be associated with a higher risk of acute seizures. The presence of this otherwise not clearly epileptiform pattern should raise the clinical suspicion for the development of acute seizures. Patients with LRDA and ipsilateral insular lesions should be carefully monitored for the development of recurrent electrographic or electroclinical seizures and status epilepticus.

An update on the pathogenesis of Hashimoto's thyroiditis.

It is 70 years since Noel Rose embarked on his pioneering studies that lead to the discovery of autoimmune thyroiditis and the elucidation of Hashimoto's thyroiditis. This short review to honour his passing focuses on the developments in our understanding of the causes and pathogenesis of HT over the last five years. Recent genetic studies have reported heritability estimates for HT and associated diseases for the first time, and emphasised the complexity of the genetic factors involved, including monogenic forms of HT. Environmental factors continue to be elucidated, especially as a side effect of drugs which modulate the immune system therapeutically. Regarding pathogenetic mechanisms, multiple cytokine networks have been identified which involve the thyroid cells in a circuit of escalating proinflammatory effects, such as the expression of inflammasome components, and an array of different defects in T regulatory cells may underlie the loss of self-tolerance to thyroid autoantigens. Finally, a number of studies have revealed fresh insights into disease associations with HT which may have both pathological and clinical significance, the most intriguing of which is a possible direct role of the autoimmune process itself in causing some of the persistent symptoms reported by a minority of patients with levothyroxine-treated HT.

Salivary gland function in women with Hashimoto's thyroiditis without xerostomia and the correlation with auto-thyroid antibodies.

BACKGROUND: Hashimoto's thyroiditis (HT) may cause salivary dysfunction in patients resulting in xerostomia, but little is known about changes in salivary function in patients with no obvious dry mouth symptoms. In this study we assessed salivary function in women with HT, who had not experienced xerostomia and, for the first time, evaluated the effects of thyroid auto-antibodies on this function.: METHODS: Sixty consecutive subjects were included, comprising 32 women (mean age, 36 ±â€Š12 years) diagnosed with HT accompanied by differentiated thyroid cancer (DTC) in the study group (HT group), along with a control group (DTC group) of 28 women (mean age, 40 ±â€Š12 years) diagnosed with DTC only. Salivary gland scintigraphy was used to assess salivary function with the semi-quantitative parameters of maximum absorption ratio and maximum secretion ratio, the decrease of which indicate impaired salivary function. Moreover, the HT and DTC groups were divided into four subgroups (Anti- HT, Anti+ HT, Anti- DTC, and Anti+ DTC), based on the presence of anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb). Finally, salivary gland semi-quantitative parameters were correlated with levels of thyroid-stimulating hormone (TSH), TGAb, and TPOAb in the HT and DTC groups. RESULTS: None of the semi-quantitative parameters examined in parotid or submandibular glands differed significantly between the HT and DTC groups. However, the maximum secretion ratio for the parotid and submandibular glands were significantly different in the subgroup comparison (p < 0.05). Furthermore, the TgAb, TPOAb, and TSH values correlated significantly with salivary excretive function (p ≤ 0.05). CONCLUSION: Women with HT without xerostomia may not have salivary functional impairment during hypothyroidism. Serum thyroid autoantibody and TSH levels may mainly influence salivary excretive function but not uptake function.

Continuous EEG Findings in Autoimmune Encephalitis.

PURPOSE: Autoimmune encephalitis (AE) is a cause of new-onset seizures, including new-onset refractory status epilepticus, yet there have been few studies assessing the EEG signature of AE. METHODS: Multicenter retrospective review of patients diagnosed with AE who underwent continuous EEG monitoring. RESULTS: We identified 64 patients (male, 39%; white, 49%; median age, 44 years); of whom, 43 (67%) were antibody-proven AE patients. Of the patients with confirmed antibody AE, the following were identified: N-methyl-D-aspartate receptor (n = 17, 27%), voltage-gated potassium channel (n = 16, 25%), glutamic acid decarboxylase (n = 6, 9%), and other (n = 4, 6%). The remaining patients were classified as probable antibody-negative AE (n = 11, 17%), definite limbic encephalitis (antibody-negative) (n = 2, 3%), and Hashimoto encephalopathy (n = 8, 13%). Fifty-three percent exhibited electrographic seizures. New-onset refractory status epilepticus was identified in 19% of patients. Sixty-three percent had periodic or rhythmic patterns; of which, 38% had plus modifiers. Generalized rhythmic delta activity was identified in 33% of patients. Generalized rhythmic delta activity and generalized rhythmic delta activity plus fast activity were more common in anti-N-methyl-D-aspartate AE (P = 0.0001 and 0.0003, respectively). No other periodic or rhythmic patterns exhibited AE subtype association. Forty-two percent had good outcome on discharge. Periodic or rhythmic patterns, seizures, and new-onset refractory status epilepticus conferred an increased risk of poor outcome (OR, 6.4; P = 0.0012; OR, 3; P = 0.0372; OR, 12.3; P = 0.02, respectively). CONCLUSION: Our study confirms a signature EEG pattern in anti-N-methyl-D-aspartate AE, termed extreme delta brush, identified as generalized rhythmic delta activity plus fast activity in our study. We found no other pattern association with other AE subtypes. We also found a high incidence of seizures among patients with AE. Finally, periodic or rhythmic patterns, seizures, and new-onset refractory status epilepticus conferred an increased risk of poor outcome regardless of AE subtype.

Seizures in autoimmune encephalitis: Findings from an EEG pooled analysis.

PURPOSE: Seizures are common in autoimmune encephalitis (AE), and an extensive work-up is required to exclude alternative etiologies. The aim of our study was to identify possible clinical/EEG peculiarities suggesting the immune-mediated origin of late-onset seizures. METHODS: Thirty patients diagnosed with AE (19 men, median age 68 years, 18 seronegative) were included. Overall 212 video-electroencephalographic (EEG) and 31 24-h ambulatory EEG (AEEG) recordings were retrospectively reviewed. Posterior dominant rhythm, interictal epileptiform discharges (IEDs), clinical (CSs) and subclinical seizures (SCSs) were analyzed. RESULTS: Six-hundred-nineteen ictal events were recorded in 19/30 subjects, mostly (568/619) during AE acute stage. Among ten patients with CSs other than faciobrachial dystonic seizures, 7 showed prominent autonomic and emotional manifestations. SCSs were detected in 11 subjects, mainly via AEEG (260/287 SCSs vs 150/332 CSs, p < 0.001). Eight patients presented seizures during hyperventilation. IEDs, documented in 21 cases, were bilateral in 14 and focal temporal in 13. Multiple ictal EEG patterns were detected in 9/19 patients, 6 of whom had both CSs and SCSs, bilateral asynchronous seizures and ictal activities arising from temporal and extra-temporal regions. No correlation was found between the lateralization of MRI alterations and that of EEG findings. CONCLUSION: Our study confirms that adult-onset, high frequency focal seizures with prominent autonomic and emotional manifestations should be investigated for AE. Multiple ictal EEG patterns could represent a 'red flag', reflecting a widespread neuronal excitability related to the underlying immune-mediated process. Finally, our work enhances the crucial role of long-lasting EEG monitoring in revealing subclinical and relapsing seizures.