Maternal Rheumatoid Arthritis (RA) is suggested to increase the risk of Autism Spectrum Disorder (ASD) in the offspring, mainly through inflammation/autoimmunity, but the association is unclear. A prospective population-based cohort study was implemented to examine the association between maternal RA and offspring ASD.

We included all children born alive in Sweden from 1995 to 2015, followed up through 2017. Diagnoses of ASD and RA were clinically ascertained from National Patient Register. We quantified the association by hazard ratios (HR) and two-sided 95% confidence intervals (CI), from Cox regression after detailed adjustment for potential confounders. We examined RA serostatus, etiological subgroups and the timing of exposure. To closer examine the underlying mechanism for the association, we included a negative control group for RA, arthralgia, with similar symptomology as RA but free from inflammation/autoimmunity.

Of 3629 children born to mothers with RA, 70 (1.94%) were diagnosed with ASD, compared to 28 892 (1.92%) of 1 503 908 children born to mothers without RA. Maternal RA before delivery was associated with an increased risk of offspring ASD (HR = 1.43, 95% CI 1.11–1.84), especially for seronegative RA (HR = 1.61, 95% CI 1.12–2.30). No similar association was observed for paternal RA, maternal sisters with RA, or RA diagnosed after delivery. Maternal arthralgia displayed as high risks for offspring ASD as did maternal RA (HR = 1.41, 95% CI 1.24–1.60).

In Sweden, maternal RA before delivery was associated with an increased risk of offspring ASD. The comparable association between maternal arthralgia and ASD risk suggests other pathways of risk than autoimmunity/inflammation, acting jointly or independently of RA.

Autoimmune encephalitis are inflammatory diseases of the CNS mediated by antibodies that attack neurotransmitter receptors or proteins on the surface of neurons, usually in the limbic system. The clinic is different according to the antineuronal Ac involved.

To make a correct differential diagnosis between autoimmune encephalitis and primary psychiatric pathologies that may be similar in symptoms through a complete study of the patient including anamnesis, physical examination, imaging tests, cerebrospinal fluid and serum studies.

Description of a clinical case. A 31-year-old female patient, with no previous history of interest, was brought to the emergency department for a suspected seizure. The previous days she had presented emotional lability, difficulty in concentration and reading, blurred vision, confusion and hemicranial headache. Two days later she returned to the emergency room for insomnia, dysarthria, difficulty in reading, comprehension, naming, and excessive rumination of her problems. Incoherent and repetitive language. The Emergency service requested to rule out a conversive disorder.

Neuropsychiatric manifestations (anxiety, depression, behavioral disturbances, insomnia, memory deficits, psychomotor agitation, mania, auditory and visual hallucinations, delusions) are the first symptom in 70% of autoimmune encephalitis due to anti-NMDA antibodies and usually respond poorly to psychiatric treatment, making the treatment of the primary cause necessary for the remission of these symptoms.

Given their increasing recognition and prevalence, autoimmune causes should always be taken into account in behavioral changes, cognitive or consciousness impairment of subacute installation, especially in young patients and once infectious, metabolic and vascular causes have been ruled out with an appropriate complementary study.

No significant relationships.

There are extremely few reported cases of OCD causing catatonia and some of those cases are possibly associated with the somewhat contentious diagnosis of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus. As there is a symptom overlap between OCD and catatonia some cases of catatonia are possibly being missed, warranting discussion regarding differential diagnosis, symptomatology, and treatment of catatonia and OCD.

We describe a case of a 18-year-old patient who developed severe catatonia secondary to OCD, possibly related to PANDAS/PANS. We discuss the complex work-up, differential diagnosis, and treatment of this patient.

Discussion of a single case and a review of catatonia literature as it relates to OCD and autoimmune disorders.

Our patient was an 18-year-old Ukrainian male who presented with sub-acute onset of decreased movement, decreased oral intake, and inability to speak. He was diagnosed with catatonia of an unclear etiology and treated with high-dose lorazepam at an outside hospital then transferred to our care. Presenting symptoms were then clarified and found to be consistent with OCD, upon which OCD treatment was initiated. The patient’s sub-acute and severe onset of OCD raised the question of a PANDAS/PANS diagnosis, which was further investigated. Ultimately, his symptoms improved with ongoing lorazepam and he was transferred to another hospital for ECT treatment.

OCD has been observed to cause catatonia in extremely rare cases. Diagnosing catatonia associated with OCD is challenging and important as catatonia is associated with significant morbidity and mortality if left untreated. Our patient improved with concurrent treatment of catatonia and OCD.

No significant relationships.

. Autoimmune encephalitis is a difficult-to-recognize, complex disease that can present with various neuropsychiatric symptoms. N-methyl-D-aspartate receptor (NMDA-r) and anti-leucine-rich glioma-inactivated 1 protein (LGI-1) subtypes of autoimmune encephalitis may present with psychiatric symptoms.

We would like to present an autoimmune encephalitis case that can be confused with conversion disorder.

A 54-year-old, female patient started to have forgetfulness ten months ago, and convulsions started five months ago. The patient had disorganized behaviors and contractions in the extremities. Diffusion MRI and brain CT images were normal. The patient had low blood sodium level. In the follow-up, her orientation was impaired and she could hardly make eye contact. As the patient’s contractions were evaluated as conversion in the first stage, 50mg/day sertraline was added to the treatment.

After cranial MRI and EEG recordings were completed, the patient was referred to the neurology department due to the suspicion of autoimmune encephalitis. In the cerebrospinal fluid examination anti-LGI-1 and anti-yo antibodies were positive. Thereupon, IV pulse steroid was given. After that her orientation and disorganized behavior improved. Then, the patient was referred to oncology department.

Limbic encephalitis may manifest as sleep disorders, short-term memory loss, conversion disorder, disorganized behaviors, slurred speech, non-epileptic seizures, sensory and motor defects. Delay in diagnosis may worsen the prognosis of possible malignancy. It should be kept in mind that the patient with a suspected conversion disorder may have limbic encephalitis.

No significant relationships.

To investigate the effect of the time spent on quarantine on distress, anxiety, depression, and somatization of chronic disease patients during the COVID-19 quarantine in Greece and the differences in these parameters between healthy individuals and chronic disease patients.

The sample consisted of 943 healthy individuals and 163 patients (respiratory, autoimmune, cardiovascular, endocrine, patients with other diseases, and patients with more than one disease) completing sociodemographic assessments as well as the 4-Dimensional Symptom Questionnaire (4DSQ) during March 30, 2020 to May 3, 2020. Pearson's correlation was used to search for the association between time spent on quarantine and the 4DSQ subscales (distress, anxiety, depression, and somatization). Independent sample T-test and Glass's Δ were used for differences between healthy individuals and chronic disease patients in these subscales, an analysis also carried out between healthy individuals and all patient subgroups.

No statistically significant correlations were noted between the 4DSQ subscales and the quarantine duration, both for the patient and the healthy individuals’ group. Chronic disease patients had significantly higher levels of distress (p = 0.001, Δ = 0.28) and somatization (p = 0.000, Δ = 0.47), but not there were no significant differences in anxiety (p = 0.098, Δ = 0.14) and depression (p = 0.052, Δ = 0.19). Concerning head-to-head comparisons between the healthy individuals’ group and each patient group, significantly higher scores in distress were found only for patients with respiratory diseases (p = 0.028, Δ = 0.42). Regarding somatization, significantly higher scores were noted for the healthy individuals’ group compared with patients with autoimmune diseases (p = 0.010, Δ = 0.62), respiratory diseases (p = 0.027, Δ = 0.42), other diseases (p = 0.003, Δ = 0.55), and more than one disease (p = 0.012, Δ = 0.60). No statistically significant differences were found in anxiety and depression.

The results of this study indicate that interventional programs for chronic disease patients during quarantine should focus on distress and somatization, not on anxiety and depression. Respiratory patients might have more supportive care needs compared with patients with other diseases.

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.

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.

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.

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.

Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) is a multifunctional ubiquitin binding and editing enzyme that regulates inflammation. Genetic studies have implicated polymorphisms within the TNFAIP3 locus to the development of numerous immune-related diseases. This study evaluated the frequencies of single-nucleotide polymorphism (SNPs) within the exonic regions of the TNFAIP3 gene and an associated point mutation from the Illumina array among a predominantly Hispanic cohort.

Genomic DNA was obtained from 721 participants and sequencing of all TNFAIP3 exons and an intergenic point mutation (rs6920220) was performed. In-vitro functional assessment was performed by transfecting mutated TNFAIP3 constructs into TNFAIP3 knockout cells containing the NF-kB luciferase reporter and stimulating with TNFα. Comparative statistics were performed with Student’s t-test for continuous variables and chi-squared test for categorical variables.

Sequencing revealed two missense SNPs, rs146534657:A>G and rs2230926:T>G, both within exon 3 of TNFAIP3, which encodes the protein’s deubiquitinating enzymatic domain. Frequencies of all three point mutations differed significantly across racial groups (χ2-test, P = 0.014 to P < 0.001). Compared to Caucasians, rs146534657:A>G was overrepresented among Hispanics (odds ratio (OR) [95% CI] 4.05 [1.24−13.18]), and rs2230926:T>G was more prevalent among African-Americans (OR [95% CI] 3.65 [1.58−8.43]). In-vitro assays confirm rs146534657:A>G and rs2230926:T>G decrease the ability of TNFAIP3 to abrogate NF-κB activation by 2-fold (P < 0.01) and 1.7-fold (P < 0.01), respectively.

This study reports the frequency of rs146534657:A>G among Hispanics and is the first to evaluate its potential physiologic impact, establishing a basis for future research as a potential biomarker among this population.

The aim of this study was to identify and evaluate demographic and clinical features of paediatric patients with postural orthostatic tachycardia syndrome in a tertiary hospital speciality clinic.

This is a retrospective review of clinical data obtained during initial outpatient evaluation.

A total of 708 patients met the evaluation criteria. Female patients outnumbered males, 3.45:1. Caucasians were over-represented at 94.1% of patients. Median age at diagnosis was 15.7 years. Joint hypermobility occurred in 57.3% of patients; 22.4% had hypermobile Ehlers–Danlos syndrome; and 34.9% had hypermobility spectrum disorder. Median age of onset of symptoms was 12.6 years in patients with hypermobility versus 13.7 years in those without (p=0.0001). Median duration of symptoms was 3.3 years with hypermobility versus 1.5 years without (p<0.00001). Putative triggers included infection in 23.6% of patients, concussion in 11.4%, and surgery/trauma in 2.8%. Concurrent inflammatory disorders were noted in 5.2% of patients. Six symptoms comprised 80% of initial patient complaints. Overall, 66% of patients subsequently had at least 10 symptoms, 50% had at least 14 symptoms, and 30% reported at least 26 symptoms. Symptoms were largely cardiovascular, gastrointestinal, and neurological. Paediatric patients with postural orthostatic tachycardia syndrome seen in a large speciality clinic are predominantly female, are mostly Caucasian, have onset of symptoms in early adolescence, and have symptoms for over two years before diagnosis. Over half of patients have joint hypermobility. More than one-third of patients have a possible autoimmune or inflammatory trigger, including infection, concussion, or surgery/trauma. Patients experience symptoms that are highly variable and multi-system in origin over the course of illness.

Statins have recently been reported to cause a rare autoimmune inflammatory and/or necrotic myopathy that begins or persists after drug cessation.

We report on 26 patients seen at a neuromuscular centre between 2005 and 2011 who demonstrated muscle weakness/myalgias and creatine kinase elevations during or after statin treatment with continuation of signs and symptoms despite statin withdrawal.

All patients were treated with immunosuppressive therapy with good response; all improved biochemically and 86% improved clinically. Sixty-five percent of patients who attempted to taper off immunosuppressive therapy relapsed. We report on a novel finding whereby five of the seven patients who underwent multiple biopsies throughout their disease demonstrated a transformation of their histological diagnosis, with four progressing from having myofibre necrosis with minimal or no inflammation to a diagnosis of polymyositis.

This study offers preliminary evidence that statin-associated necrotizing myopathy and statin-associated polymyositis may not be separate entities but are part of the same pathophysiological spectrum. Both entities respond well to immunosuppression.