Epilepsy and other seizure disorders in acute psychiatric inpatients.

BACKGROUND: It is well known that patients with epilepsy have a high rate of psychiatric comorbidity. However, studies exploring epilepsy in psychiatric cohorts are scarce. The aim of this study was to examine the prevalence of seizure disorders in acute psychiatric inpatients. METHODS: This is a cross-sectional study performed in a catchment-area based acute psychiatric department. All patients (age > 18) admitted during September 2011 - March 2012 were eligible for inclusion. Consenting patients were screened for a life-time history of epilepsy or seizures using self-reported questionnaire data and diagnostic codes for epilepsy in hospital and National registries. Patients scoring positive to one or more of these screening criteria underwent a thorough diagnostic validation (chart review), and the seizure disorders were classified as epilepsy, acute symptomatic seizures and/or psychogenic non-epileptic seizures according to current definitions. RESULTS: A total of 380 out of 591 (64.3%) consecutively admitted patients consented to participate in the study. Eighty-nine patients (23.4%) scored positive to one or more screening criteria. Fifteen (3.9%) were classified with epilepsy, 21 (5.5%) with acute symptomatic seizures and 9 (2.4%) with psychogenic non-epileptic seizures. CONCLUSIONS: This is the first study to report on the prevalence of seizure disorders in acute psychiatric inpatients. The life-time prevalence of epilepsy in this cohort of patients is five - six times as high as reports in the general population. These findings underscore the need for the clinical psychiatrist to have comprehensive knowledge on the interface between epileptology and psychiatry. TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT01415323 .

A young man with convulsive laughter. / En ung mann med krampaktig latter.

BACKGROUND: Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) can manifest with a wide range of neurological and psychiatric symptoms. CASE PRESENTATION: A previously healthy man in his late twenties was admitted several times over the course of half a year. He had acute episodes of reduced consciousness, involuntary movements and psychotic symptoms (e.g. hallucinations and delusions). Initial examinations were normal except for a positive urine drug screen (tetrahydrocannabinol), and the patient was diagnosed with cannabinoid intoxication. During the next admission cerebrospinal fluid analysis showed mild pleocytosis. Screening for anti-neuronal antibodies was negative, but anti-thyroid peroxidase antibodies were detected in serum and cerebrospinal fluid. He was successfully given steroid treatment on a tentative diagnosis of SREAT, but relapsed when the steroids were discontinued. After receiving a prolonged steroid treatment with gradual dose reduction over a year, he remains symptom-free 18 months after treatment discontinuation. INTERPRETATION: The diagnostic delay might have been mitigated with an earlier inclusion of neuroimmunological disorders in the differential diagnosis. Unexplained pleocytosis in the cerebrospinal fluid in the presence of paroxysmal neuropsychiatric symptoms should trigger an investigation that includes autoimmune encephalopathies.

Biomarkers of Autoimmunity in Acute Psychiatric Disorders.

OBJECTIVE: Previous studies have suggested that autoantibodies associated with systemic autoimmune disorders are more prevalent in patients with psychotic and affective disorders compared with healthy control subjects. However, most positive studies addressing this issue have been limited by small sample sizes and lack of correction for confounding factors. The authors aimed to assess the prevalence of several autoantibodies in patients admitted to acute psychiatric inpatient care and investigate whether patients with psychotic and affective disorders have an increased prevalence of autoantibodies compared with psychiatric patients admitted for other reasons. METHODS: Five hundred eighty-five patients were screened for the presence of antinuclear antibodies (ANA), anticardiolipin and antibeta2-glycoprotein, antithyroid peroxidase (anti-TPO), antitissue transglutaminase IgA, antigliadin deamidated peptide IgG, and rheumatoid factor IgM (RF). Differences in prevalence between patients with nonaffective psychoses (N=105), bipolar disorders (N=78), unipolar depressive disorders (N=146), and other reasons for admission (N=256) were assessed using chi-square tests and logistic regression models. RESULTS: One or more autoantibodies were present in 26.2% of the patients, including ANA (9.4%), RF (9.2%), and anti-TPO (5.6%). Autoantibody prevalence increased with age (odds ratio=1.21, 95% CI=1.09-1.35) and smoking status (odds ratio=1.99, 95% CI=1.04-3.82) but was not associated with a diagnosis of a psychotic or affective disorder. CONCLUSIONS: Autoimmune autoantibodies seem to be equally prevalent in patients with acute psychiatric conditions with and without psychotic and affective disorders. This result challenges the idea that these autoantibodies have specificity for certain psychiatric disorders.

Differences between counties in the prescribing of clozapine. / Fylkesvise forskjeller i forskrivning av klozapin.

BACKGROUND: Norwegian national guidelines recommend that clozapine be offered to patients with schizophrenia after two failed attempts with other antipsychotic drugs. One of the main objectives for the introduction of clinical pathways in mental health care is to provide an equal service to patients irrespective of where in the country they live. We wished to investigate the prescribing level of clozapine in various Norwegian counties. MATERIAL AND METHOD: We retrieved aggregated data from the Norwegian Prescription Database, the Norwegian Patient Registry and Statistics Norway on prescribing of clozapine, number of patients in contact with the specialist health service with the diagnosis schizophrenia, and population figures for 2016. RESULTS: Nationwide in 2016, there were 50 users of clozapine per 100 000 inhabitants (95 % confidence interval (CI) 48-52). The number of users was highest in Troms county (76 (95 % CI 63-89) per 100 000 inhabitants) and lowest in Akershus county (38 (95 % CI 33-43) per 100 000 inhabitants). We found no significant correlation between the prescribing rate for clozapine and the proportion of the population in the county who were undergoing treatment for schizophrenia in the specialist health service. INTERPRETATION: Prescribing of clozapine varies among Norwegian counties and is not correlated with the proportion of the population who are undergoing treatment for schizophrenia in the specialist health service. Different levels of implementation of the national guidelines constitute a possible explanation for the geographic differences.

The significance of anti-neuronal antibodies for acute psychiatric disorders: a retrospective case-controlled study.

BACKGROUND: The clinical significance of anti-neuronal antibodies in patients with psychiatric disorders, but without encephalitis, remains unknown. In patients admitted to acute psychiatric inpatient care we aimed to identify clinical features distinguishing anti-neuronal antibody positive patients from matched controls. RESULTS: Patients who were serum-positive to N-methyl D-aspartate receptor (NMDAR) (n = 21), contactin-associated protein 2 (CASPR2) (n = 14) and/or glutamic acid decarboxylase 65 (GAD65) (n = 9) antibodies (cases) were age and sex matched (1:2) with serum-negative patients from the same cohort (controls). The prevalence and severity of psychiatric symptoms frequently encountered in NMDAR, CASPR2 and GAD65 antibody associated disorders were compared in cases and controls. NMDAR, CASPR2 and GAD65 antibody positive patients did not differ in their clinical presentation from matched serum negative controls. CONCLUSION: In this cohort, patients with and without NMDAR, CASPR2 and GAD65 antibodies admitted to acute psychiatric inpatient care had similar psychiatric phenotypes. This does not exclude their clinical relevance in subgroups of patients, and studies further investigating the clinical significance of anti-neuronal antibodies in patients with psychiatric symptomatology are needed.

Synapsin-antibodies in psychiatric and neurological disorders: Prevalence and clinical findings.

OBJECTIVE: To study the prevalence of autoantibodies to synapsin in patients with psychiatric and neurological disorders and to describe clinical findings in synapsin antibody positive patients. METHODS: Sera of 375 patients with different psychiatric and neurological disorders and sera of 97 healthy controls were screened (dilution 1:320) for anti-synapsin IgG using HEK293 cells transfected with rat synapsin Ia. Positive sera were further analyzed by immunoblots with brain tissue from wild type and synapsin knock out mice and with HEK293 cells transfected with human synapsin Ia and Ib. Binding of synapsin IgG positive sera to primary neurons was studied using murine hippocampal neurons. RESULTS: IgG in serum from 23 (6.1%) of 375 patients, but from none of the 97 healthy controls (p=0.007), bound to rat synapsin Ia transfected cells with a median (range) titer of 1:1000 (1:320-1:100,000). Twelve of the 23 positive sera reacted with a protein of the molecular size of synapsin I in immunoblots of wild type but not of synapsin knock out mouse brain tissue. Out of 19/23 positive sera available for testing, 13 bound to human synapsin Ia and 16 to human synapsin Ib transfected cells. Synapsin IgG positive sera stained fixed and permeabilized murine hippocampal neurons. Synapsin IgG positive patients had various psychiatric and neurological disorders. Tumors were documented in 2 patients (melanoma, small cell lung carcinoma); concomitant anti-neuronal or other autoantibodies were present in 8 patients. CONCLUSIONS: Autoantibodies to human synapsin Ia and Ib are detectable in a proportion of sera from patients with different psychiatric and neurological disorders, warranting further investigation into the potential pathophysiological relevance of these antibodies.

Onconeural Antibodies in Acute Psychiatric Inpatient Care.

Paraneoplastic neurological disorders associated with onconeural antibodies often appear with neuropsychiatric symptoms. To study the prevalence of onconeural antibodies in patients admitted to acute psychiatric inpatient care, the serum of 585 such patients was tested for antibodies targeting MOG, GLRA1B, DPPX, GRM1, GRM5, DNER, Yo, ZIC4, GAD67, amphiphysin, CV2, Hu, Ri, Ma2, and recoverin. Only one sample was positive (antirecoverin IgG). The present findings suggest that serum onconeural antibody positivity is rare among patients acutely admitted for inpatient psychiatric care. The clinical implications of this finding are discussed.

What is the significance of onconeural antibodies for psychiatric symptomatology? A systematic review.

BACKGROUND: Patients with intracellular onconeural antibodies may present with neuro-psychiatric syndromes. We aimed to evaluate the evidence for an association between well-characterized onconeural antibodies and psychiatric symptoms in patients with and without paraneoplastic central nervous system syndromes. METHODS: Eligible studies were selected from 1980 until February 2017 according to standardized review criteria and evaluated using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). We included studies describing the psychiatric symptomatology of onconeural antibody positive patients and the prevalence of onconeural antibodies in patients with psychiatric disorders. RESULTS: Twenty-seven studies met the inclusion criteria. Six studies reported on the prevalence of well-characterized onconeural antibodies in patients with different psychiatric disorders, ranging from 0% to 4.9%. Antibody prevalence in controls was available from three studies, ranging from 0% to 2.8%. Data heterogeneity precluded a meta-analysis. Two cerebrospinal fluid studies found well-characterized onconeural antibodies in 3.5% and 0% of patients with psychotic and depressive syndromes, respectively. CONCLUSIONS: The available evidence suggests that the prevalence of well-characterized onconeural antibodies in patients with psychiatric disorders is generally low. However, the question whether onconeural antibodies are important in select patients with a purely psychiatric phenotype needs to be addressed by appropriately designed studies in the future.

Cerebrospinal fluid cytokines in geriatric patients with depressive disorders: A retrospective case-control study.

Central nervous system inflammation might play a role in patients with depressive disorders. This hypothesis is supported by studies reporting increased cerebrospinal fluid levels of the inflammatory markers interleukin (IL)-6, IL-8 and tumor necrosis factor alpha (TNF-α) in patients with ongoing depression. In this case-control study, we aimed to examine whether these findings also applied to depressed patients in a geriatric population. Cerebrospinal fluid cytokine analyses were performed on 15 patients (age >60 years) with depressive disorders and 45 age- and sex matched controls (patients with headache or idiopathic facial palsy). IL-6, IL-8, IL-10, TNF-α, monocyte chemoattractant protein-1 and transforming growth factor beta 1 were included in the statistical analyses. Patients with depression had significantly lower cerebrospinal fluid levels of IL-6 as compared to controls (p = 0.014) in the univariate analysis. The finding was, however, no longer statistically significant after correction for age and body mass index (p = 0.097). Overall, this study indicates that the cytokines included in this study are not significantly altered in geriatric patients with depression. Future studies exploring cerebrospinal fluid cytokine levels should include corrections for possible confounding factors.

High prevalence of subclinical rheumatic heart disease in pregnant women in a developing country: an echocardiographic study.

OBJECTIVES: Pregnant women with rheumatic heart disease (RHD) carry a high risk of morbidity and mortality. In this study the prevalence of subclinical RHD in pregnant women in Keren, Eritrea was assessed using echocardiography. METHODS AND RESULTS: A prospective cross sectional survey of pregnant women attending a midwife consultation was carried out by two specially trained medical students and an experienced cardiologist. The women were screened by the medical students using echocardiography. All recordings were reviewed and evaluated by the experienced cardiologist before a final diagnosis was given. Eight of the 348 screened women had definite RHD. This corresponds to a prevalence of 2.3%, 95% CI (0.7-3.9). CONCLUSION: 2.3% of the pregnant women in Keren were found to have subclinical RHD.

Subtle Phenotype Differences in Psychiatric Patients With and Without Serum Immunoglobulin G Antibodies to Synapsin.

The discovery that antibodies targeting neuronal antigens can induce severe psychiatric symptoms has been a significant progress in the understanding of psychiatric disorders. Antibodies targeting synapsin I in serum and cerebrospinal fluid (CSF) were first reported in 2015 in a patient with limbic encephalitis. Because of its regulatory function for neurotransmitter release, synapsin I has been suggested to play a role in psychiatric disorders. It is, however, unknown whether or not synapsin antibodies are of clinical significance in patients with psychiatric disorders. In the present study, we aimed to investigate if synapsin I immunoglobulin (Ig)G serum antibody positive patients admitted to acute psychiatric care have a different psychiatric phenotype than synapsin IgG antibody negative patients. A total of 13 anti-synapsin positive patients were matched for age, sex, and psychiatric diagnosis with 39 anti-synapsin negative patients from the same cohort. The groups were compared regarding 11 clinical features frequently seen in anti-neuronal antibody associated disorders. Anti-synapsin positive patients had higher agitation scores as measured with the Positive and Negative Syndrome Scale Excited Component [median (interquartile range) 11 (8) versus 7 (7), p = 0.04] compared to controls. However, the absolute scores were low in both groups, and the difference may not be clinically significant. Other clinical features assessed (e.g. hallucinations, delusions) did not differ between groups. We conclude that synapsin serum IgG antibodies lack syndrome specificity in patients admitted to acute psychiatric inpatient care. However, further studies addressing functional effects of synapsin antibodies are needed to conclude whether or not they have a pathophysiological relevance.

Epitope specificity of anti-synapsin autoantibodies: Differential targeting of synapsin I domains.

OBJECTIVE: To identify the specific domains of the presynaptic protein synapsin targeted by recently described autoantibodies to synapsin. METHODS: Sera of 20 and CSF of two patients with different psychiatric and neurological disorders previously tested positive for immunoglobulin (Ig)G antibodies to full-length synapsin were screened for IgG against synapsin I domains using HEK293 cells transfected with constructs encoding different domains of rat synapsin Ia. Additionally, IgG subclasses were determined using full-length synapsin Ia. Serum and CSF from one patient were also screened for IgA autoantibodies to synapsin I domains. Sera from nine and CSF from two healthy subjects were analyzed as controls. RESULTS: IgG in serum from 12 of 20 IgG synapsin full-length positive patients, but from none of the healthy controls, bound to synapsin domains. Of these 12 sera, six bound to the A domain, five to the D domain, and one to the B- (and possibly A-), D-, and E-domains of synapsin I. IgG antibodies to the D-domain were also detected in one of the CSF samples. Determination of IgG subclasses detected IgG1 in two sera and one CSF, IgG2 in none of the samples, IgG3 in two sera, and IgG4 in eight sera. One patient known to be positive for IgA antibodies to full-length synapsin had IgA antibodies to the D-domain in serum and CSF. CONCLUSIONS: Anti-synapsin autoantibodies preferentially bind to either the A- or the D-domain of synapsin I.