Inflammatory cerebrospinal fluid markers in schizophrenia spectrum disorders: A systematic review and meta-analysis of 69 studies with 5710 participants.

BACKGROUND: There is increasing evidence of immune dysregulation and neuroinflammation occurring in schizophrenia. The aim of this study is to combine studies on routine CSF parameters, as well as cytokines and inflammatory proteins, in individuals with schizophrenia spectrum disorders. METHODS: CSF parameters were summated and inverse variance meta-analyses using a random effects model were performed comparing mean difference or odds ratios. Between study heterogeneity was assessed using the I2 statistic. Quality assessment and sensitivity analyses were performed. RESULTS: There were 69 studies of 5710 participants, including 3180 individuals with schizophrenia spectrum disorders. Averaged CSF parameters were within normal limits, however, between 3.1 % and 23.5 % of individual cases with schizophrenia spectrum disorders had an abnormal CSF result: Protein (abnormal in 23.5 % cases), albumin (in 18.5 %), presence of oligoclonal bands (in 9.3 %), white blood cell count (in 3.6 %), and IgG levels (3.1 %). Meta-analysis of 55 studies with non-psychiatric controls demonstrated a significant increase in CSF total protein (MD: 3.50, CI: 0.12-6.87), albumin ratio (MD: 0.55, CI: 0.02-0.09), white cell count (MD: 0.25, CI: 0.05-0.46), IL-6 (SMD: 0.53, CI: 0.29 to 0.77) and IL-8 (SMD: 0.56, CI: 0.11 to 1.01). Sensitivity analysis did not alter findings. CONCLUSION: Abnormal CSF parameters, cytokines and inflammatory proteins were found in a significant proportion of individuals with schizophrenia spectrum disorders. This may indicate alterations to blood brain barrier function and permeability, CSF flow dynamics or neuroinflammation. Further research is needed to explore these potential mechanisms.

Anti-glutamic acid decarboxylase antibody screening in first-episode psychosis.

OBJECTIVE: The Royal Australian and New Zealand College of Psychiatrists recommends screening for a range of antibodies in first-episode psychosis, including anti-glutamic acid decarboxylase antibodies. Glutamic acid decarboxylase antibody-associated encephalitis occurs with high antibody titres and may cause cognitive dysfunction, seizures and psychiatric symptoms. However, glutamic acid decarboxylase antibodies are more frequently found in lower titre in association with other autoimmune disorders (such as diabetes mellitus type 1) and in healthy individuals. The utility of testing unselected populations of consumers with psychosis is unclear. The psychiatric manifestations of this disorder are also poorly described. METHODS: First, systematic review of cohort and case-control studies that tested for IgG glutamic acid decarboxylase antibodies in psychiatric populations was conducted. Random-effects meta-analysis of odds ratio for antibody positivity in cases with psychosis and controls assessed prevalence. Second, literature review of all published cases and case series of glutamic acid decarboxylase antibody-associated limbic encephalitis was assessed for frequency and description of psychotic symptoms. RESULTS: There were 17 studies, in which 2754 individuals with psychotic disorders were tested for glutamic acid decarboxylase IgG antibodies. Thirty-one consumers with psychosis (0.7%) had positive glutamic acid decarboxylase antibodies compared to 24 controls (1.0%), all at low titre and not fulfilling diagnostic criteria for autoimmune encephalitis. Meta-analysis found no significant difference in rates of glutamic acid decarboxylase antibody positivity (odds ratio = 1.8, 95% confidence interval: [0.90, 3.63]). Literature review found 321 cases of glutamic acid decarboxylase antibody-associated limbic encephalitis, with psychosis in 15 (4.3%) cases. Clinical screening would have identified all cases that presented to psychiatric services. CONCLUSION: Glutamic acid decarboxylase antibodies were uncommon in consumers with psychosis, with no significant difference in prevalence from controls and no cases of encephalitis identified. In cases with established glutamic acid decarboxylase antibody-associated limbic encephalitis, psychotic symptoms were uncommon and identifiable by clinical assessment. Targeted antibody testing guidelines should be further considered.

Multiterritorial strokes in the setting of spontaneous heparin-induced thrombocytopaenia syndrome.

We present a case study of a 38-year-old man who developed arterial and venous thrombi, resulting in multiterritorial strokes, a pulmonary embolus and a cerebral venous sinus thrombosis in the setting of spontaneous heparin-induced thrombocytopaenia syndrome.

Response to treatment in NMOSD: the Australasian experience.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is associated with significant morbidity and mortality. Several therapies have been recommended for NMOSD and more recently clinical trials have demonstrated efficacy for three monoclonal antibody therapies. We present a retrospective observational study of treatment response in NMOSD. METHODS: This was a retrospective, unblinded, observational study of treatment efficacy for rituximab and traditional immunosuppressive therapy in patients with AQP4 antibody positive NMOSD. Treatment efficacy was assessed using annualised relapse rates (ARR), time to first relapse and expanded disability status scale (EDSS) scores. RESULTS: Complete relapse and treatment data were available for 43/68 (63%) of AQP4 antibody positive NMOSD cases covering 74 episodes of treatment. In a time to first relapse analysis rituximab showed a risk ratio of 0.23 (95% CI 0.08 - 0.65) when compared with no treatment and there was a non-significant reduction in ARR of 35% compared to pre-treatment. ß-interferon (p = 0.0002) and cyclophosphamide (p = 0.0034) were associated with an increased ARR compared to pre-treatment. Rituximab (median 4.0 [range 0.0 - 7.0]; p = 0.042) and traditional immunosuppressive therapy (median 4.0 [range 0.0 - 8.0]; p = 0.016) were associated with a lower final EDSS compared to ß-interferon (median 6.0 [range 4.0 - 7.5]). CONCLUSIONS: These data provide additional support for the use of rituximab in preference to traditional immunosuppressive agents and MS disease modifying therapies as first line treatment of NMOSD.

Tardive Seizures After Electroconvulsive Therapy.

OBJECTIVES: Seizures that occur spontaneously after termination of an electroconvulsive therapy (ECT) seizure are termed tardive seizures. They are thought to be a rare complication of ECT, influenced by risk factors that affect seizure threshold. However, there has been limited review of tardive seizures with modified ECT. We aimed to review the literature to provide clinical guidance for the use of ECT after tardive seizures. METHODS: PubMed, EMBASE, PsycInfo, and CINAHL databases were searched from inception to May 2021 to identify cases of modified ECT, with evidence of a seizure occurring within 7 days of a terminated ECT seizure. Data for demographic, medical, pharmacological, anesthetic, and ECT variables as well as management strategies were collected. RESULTS: There have been 39 episodes of modified ECT-related tardive seizures published over a period of 40 years. In 97.4% of cases, there was at least 1 identified potential risk factor for seizures, including use of a seizure-lowering medication and/or preexisting neurological injury. Major complications were uncommon (<15% of cases); however, 1 fetal death and 1 subsequent suicide were reported. No case was diagnosed with epilepsy, although around 20% continued on antiepileptic medications. More than half of the included patients were retrialed on ECT, with only 15% developing further tardive seizures. CONCLUSIONS: Seizures that occurred spontaneously after the termination of an ECT seizure are a rare complication of modified ECT. Recommencing ECT after a tardive seizure may occur after review of modifiable seizure risk factors and with consideration of antiepileptic medication and extended post-ECT monitoring.

Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis.

Rhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety of genetic disorders predispose to rhabdomyolysis through different pathogenic mechanisms, particularly in patients with recurrent episodes. However, most cases remain without a genetic diagnosis. Here we present six patients who presented with severe and recurrent rhabdomyolysis, usually with onset in the teenage years; other features included a history of myalgia and muscle cramps. We identified 10 bi-allelic loss-of-function variants in the gene encoding obscurin (OBSCN) predisposing individuals to recurrent rhabdomyolysis. We show reduced expression of OBSCN and loss of obscurin protein in patient muscle. Obscurin is proposed to be involved in sarcoplasmic reticulum function and Ca2+ handling. Patient cultured myoblasts appear more susceptible to starvation as evidenced by a greater decreased in sarcoplasmic reticulum Ca2+ content compared to control myoblasts. This likely reflects a lower efficiency when pumping Ca2+ back into the sarcoplasmic reticulum and/or a decrease in Ca2+ sarcoplasmic reticulum storage ability when metabolism is diminished. OSBCN variants have previously been associated with cardiomyopathies. None of the patients presented with a cardiomyopathy and cardiac examinations were normal in all cases in which cardiac function was assessed. There was also no history of cardiomyopathy in first degree relatives, in particular in any of the carrier parents. This cohort is relatively young, thus follow-up studies and the identification of additional cases with bi-allelic null OBSCN variants will further delineate OBSCN-related disease and the clinical course of disease.

MRI Patterns Distinguish AQP4 Antibody Positive Neuromyelitis Optica Spectrum Disorder From Multiple Sclerosis.

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the CNS. Overlap in the clinical and MRI features of NMOSD and MS means that distinguishing these conditions can be difficult. With the aim of evaluating the diagnostic utility of MRI features in distinguishing NMOSD from MS, we have conducted a cross-sectional analysis of imaging data and developed predictive models to distinguish the two conditions. NMOSD and MS MRI lesions were identified and defined through a literature search. Aquaporin-4 (AQP4) antibody positive NMOSD cases and age- and sex-matched MS cases were collected. MRI of orbits, brain and spine were reported by at least two blinded reviewers. MRI brain or spine was available for 166/168 (99%) of cases. Longitudinally extensive (OR = 203), "bright spotty" (OR = 93.8), whole (axial; OR = 57.8) or gadolinium (Gd) enhancing (OR = 28.6) spinal cord lesions, bilateral (OR = 31.3) or Gd-enhancing (OR = 15.4) optic nerve lesions, and nucleus tractus solitarius (OR = 19.2), periaqueductal (OR = 16.8) or hypothalamic (OR = 7.2) brain lesions were associated with NMOSD. Ovoid (OR = 0.029), Dawson's fingers (OR = 0.031), pyramidal corpus callosum (OR = 0.058), periventricular (OR = 0.136), temporal lobe (OR = 0.137) and T1 black holes (OR = 0.154) brain lesions were associated with MS. A score-based algorithm and a decision tree determined by machine learning accurately predicted more than 85% of both diagnoses using first available imaging alone. We have confirmed NMOSD and MS specific MRI features and combined these in predictive models that can accurately identify more than 85% of cases as either AQP4 seropositive NMOSD or MS.

An Australian State-Based Cohort Study of Autoimmune Encephalitis Cases Detailing Clinical Presentation, Investigation Results, and Response to Therapy.

Introduction: Autoimmune encephalitis is a disorder associated with antibodies directed against central nervous system proteins with variable clinical features. This study aims to add to knowledge of the disease by reporting the details of a cohort of patients with autoimmune encephalitis in Queensland, Australia. Methodology: We surveyed patients with autoimmune encephalitis diagnosed and managed through public hospitals in Queensland, Australia between 2010 and the end of 2019. Cases were identified via case detection through a centralized diagnostic neuroimmunology laboratory (Division of Immunology, HSQ Pathology Queensland Central Laboratory, Brisbane, Queensland, Australia) and a survey of neurologists. Data including demographic details, clinical presentation, investigation results, treatments including immune therapy and outcomes was collected. Results: Sixty cases of antibody positive autoimmune encephalitis were identified. Twenty-eight were of anti-NMDA-receptor encephalitis with other cases associated with antibodies against LGi1, Caspr2, glycine receptor, DPPX, GABAB receptor, IgLON5, GFAP, and SOX1. The number of diagnosed cases, especially of anti-NMDA-receptor encephalitis has markedly increased over the period 2017 to 2019. Clinical presentations were marked by heterogeneous symptom complexes and prolonged hospital admissions. Imaging studies were largely normal or non-specific. There was a response to immune therapy and a low mortality rate. Most cases affected by this disorder were left with ongoing symptoms associated with mild disability. Conclusion: Autoimmune encephalitis in Queensland, Australia is an increasingly common but complex clinical entity marked by heterogeneous presentations, response to immune therapy and outcome results marked by low mortality and incomplete recovery.

A case of IVIg responsive paraneoplastic SOX1 peripheral neuropathy in a male with breast carcinoma.

BACKGROUND AND AIMS: SOX1 antibodies are generally associated with small cell lung cancer and anti-Hu antibody overlap is common. This case demonstrates isolated anti-SOX1 antibodies with an uncommon tumor type, and relapse of a paraneoplastic syndrome with recurrence of tumor. METHODS: We describe a case of a 65-year-old male with a paraneoplastic peripheral neuropathy and anti-SOX1 antibody positivity in the context of a prior male breast Grade 2 ductal carcinoma, in remission at the time of the initial neurological presentation. RESULTS: Treatment response to intravenous immunoglobulin (IVIg) was demonstrated. After period of clinical stability on IVIg in the context of remission of breast carcinoma, the patient experienced a relapse of his neuropathy. This was associated with tumor recurrence and again responded to tumor excision, radiotherapy and IVIg. INTERPRETATION: Male breast carcinoma has not previously been associated with anti-SOX1 antibody positive paraneoplastic neuropathy.

Voltage-gated potassium channel blanket testing in first-episode psychosis: Diagnostic nihilism?

OBJECTIVE: Voltage-gated potassium channel antibodies are implicated in limbic encephalitis and currently included in first-episode psychosis organic screening guidelines. Individuals with high-positive voltage-gated potassium channel titres most commonly present with neurological symptoms as well as sleep, cognitive, behaviour, psychosis and mood disturbance. The significance of low-positive voltage-gated potassium channel antibody titres in psychiatric patients is unclear and has not been previously examined. We aim to describe a statewide cohort of psychiatric patients with low- and high-positive voltage-gated potassium channel titres and explore if this finding influenced clinical management and patient outcomes. METHODS: A retrospective review of all voltage-gated potassium channel antibodies testing performed in public psychiatric services in Queensland, Australia, with comparison of the clinical presentation and long-term outcomes of low- and high-positive voltage-gated potassium channel titre cases. Specific antigen targets (leucine-rich glioma-inactivated protein 1 and contactin-associated protein 2 antibodies) were also assessed. RESULTS: The overall prevalence of voltage-gated potassium channel antibody positivity in Queensland, public, psychiatric service testing was 0.3% (14/4098), with 12 cases of low-positive voltage-gated potassium channel titre, 2 cases of high-positive (leucine-rich glioma-inactivated protein 1 antibody positive) cases and a voltage-gated potassium channel negative contactin-associated protein 2 antibody positive case. No low-positive case developed neurological abnormalities or had abnormal paraclinical investigations. In comparison, both high-positive voltage-gated potassium channel/leucine-rich glioma-inactivated protein 1 cases and the contactin-associated protein 2 antibody positive case rapidly developed neurological symptoms, had abnormal paraclinical testing and improved only with immunotherapy. There was no later development of encephalitic symptoms in the low-positive cases over an average of 1067 days follow-up. CONCLUSION: Voltage-gated potassium channel antibody-associated limbic encephalitis was rare, and always associated with high antibody titres. Low-positive titres were not associated with the development of encephalitis over a long period of follow-up. The value of universal voltage-gated potassium channel antibody screening is unclear, and further prospective studies in first-episode psychosis populations are required.

Psychiatric management of anti-NMDAR encephalitis: a cohort analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Status epilepticus from GABABR antibody positive encephalitis due to de novo mixed small cell and adenocarcinoma of the prostate.

We present a case study of a 67-year-old man who presented with a new onset of recurrent tonic-clonic seizures. He had tested positive to gamma-aminobutyric acid B receptor antibodies in his blood and cerebrospinal fluid, and subsequent CT imaging and transrectal biopsy confirmed the presence of a locally advanced mixed small cell and Gleason 9 adenocarcinoma of the prostate. His seizures remained resistant to treatment with multiple antiepileptic drugs, including sodium valproate, clobazam, topiramate, carbamazepine, phenytoin and lacosamide. He progressed to status epilepticus, which required intravenous immunoglobulin and steroids, followed by plasma exchange 1 week later. The status epilepticus was refractory and required multiple admissions to the intensive care unit.

Relapse Patterns in NMOSD: Evidence for Earlier Occurrence of Optic Neuritis and Possible Seasonal Variation.

Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) show overlap in their clinical features. We performed an analysis of relapses with the aim of determining differences between the two conditions. Cases of NMOSD and age- and sex-matched MS controls were collected from across Australia and New Zealand. Demographic and clinical information, including relapse histories, were recorded using a standard questionnaire. There were 75 cases of NMOSD and 101 MS controls. There were 328 relapses in the NMOSD cases and 375 in MS controls. Spinal cord and optic neuritis attacks were the most common relapses in both NMOSD and MS. Optic neuritis (p < 0.001) and area postrema relapses (P = 0.002) were more common in NMOSD and other brainstem attacks were more common in MS (p < 0.001). Prior to age 30 years, attacks of optic neuritis were more common in NMOSD than transverse myelitis. After 30 this pattern was reversed. Relapses in NMOSD were more likely to be treated with acute immunotherapies and were less likely to recover completely. Analysis by month of relapse in NMOSD showed a trend toward reduced risk of relapse in February to April compared to a peak in November to January (P = 0.065). Optic neuritis and transverse myelitis are the most common types of relapse in NMOSD and MS. Optic neuritis tends to occur more frequently in NMOSD prior to the age of 30, with transverse myelitis being more common thereafter. Relapses in NMOSD were more severe. A seasonal bias for relapses in spring-summer may exist in NMOSD.

Screening for anti-NMDAR encephalitis in psychiatry.

Anti-NMDAR encephalitis most commonly presents to psychiatric services, so early identification of this disorder is essential. We aim to validate the two screening criteria (Scott et al. and Herken and Pruss) which have been proposed to identify first episode psychosis patients who should have anti-NMDAR antibody testing. The performance of the screening criteria were assessed using anti-NMDAR encephalitis cases published in the literature, and antibody positive and negative cases from a state-wide cohort (Queensland, Australia). Sensitivity, specificity and area under receiver operator characteristic curve analysis was performed. There were 258 anti-NMDAR encephalitis cases and 103 control cases, which demonstrated high performance of both Scott et al. "screening recommended" criteria (sensitivity 97.3%, specificity 85.4%, AUC 0.914) and Herken and Pruss "yellow flags" criteria (sensitivity 91.5%, specificity 83.5%, AUC 0.875). These criteria remained accurate when neurological variables were excluded, and in cases without psychosis. The Scott et al. "screening not recommended", and Herken and Pruss "red flags" criteria did not demonstrate clinical utility for first episode psychosis case screening. The screening criteria with good performance identify an atypical picture of psychiatric presentation with increased risk of anti-NMDAR positivity prior to overt neurological symptoms or investigations and may be beneficial to include in the routine psychiatric assessment process.

The clinical profile of NMOSD in Australia and New Zealand.

Neuromyelitis optica spectrum disorders (NMOSD) are an inflammation of the central nervous system associated with autoantibodies to aquaporin-4. We have undertaken a clinic-based survey of NMOSD in the Australia and New Zealand populations with the aim of characterising the clinical features and establishing the value of recently revised diagnostic criteria. Cases of possible NMOSD and age and sex-matched controls with multiple sclerosis (MS) were referred from centres across Australia and New Zealand. Cases were classified as NMOSD if they met the 2015 IPND criteria and remained as suspected NMOSD if they did not. Clinical and paraclinical data were compared across the three groups. NMOSD was confirmed in 75 cases and 89 had suspected NMOSD. There were 101 controls with MS. Age at onset, relapse rates and EDSS scores were significantly higher in NMOSD than in MS. Lesions and symptoms referable to the optic nerve were more common in NMOSD whereas brainstem, cerebellar and cerebral lesions were more common in MS. Longitudinally extensive spinal cord lesions were seen in 48/71 (68%) of cases with NMOSD. Elevations of CSF, white cell count and protein were more common in NMOSD. We have confirmed a clinical pattern of NMOSD that has been seen in several geographical regions. We have demonstrated the clinical utility of the current diagnostic criteria. Distinct patterns of disease are evident in NMOSD and MS, but there remains a large number of patients with NMOSD-like features who do not meet the current diagnostic criteria for NMOSD and remain a diagnostic challenge.

Serum and CSF Anti-NMDAR Antibody Testing in Psychiatry.

OBJECTIVE: The authors examined and compared the clinical presentation of CSF positive and negative N-methyl-d-aspartate receptor (NMDAR) antibody. METHODS: The investigators performed a retrospective chart review of NMDAR-antibody-positive cases (serum or CSF) involving patients presenting to psychiatric services from 2010 to 2018 in Queensland, Australia. Presentation, progress, investigations, and efficacy of treatment are detailed. RESULTS: There were 24 serum or CSF NMDAR-antibody-positive cases and three equivocal serum results. High rates of prodromal cognitive deficits, catatonia, speech disturbance, and antipsychotic sensitivity were observed in the 16 CSF NMDAR-antibody-positive case patients and two CSF NMDAR-antibody-negative case patients, all evident before neurological deterioration with seizures, movement disorder, and autonomic disturbance occurring in the weeks following admission. The majority of these patients (N=17) were treated successfully with immunomodulatory therapy. The nine remaining patients, who were CSF NMDAR antibody negative or equivocal, did not demonstrate any of these features and improved with psychiatric care alone. CONCLUSIONS: These findings suggest that traditional psychiatric care may be appropriate for patients with isolated psychiatric symptoms who have positive serum NMDAR testing when CSF is negative and there are no key clinical features such as cognitive deficits, catatonia, speech disturbance, and antipsychotic sensitivity. However, if these key features are present, a trial of immunomodulatory treatment should be considered with repeated examination of CSF for neuronal antibodies.

EEG findings in NMDA encephalitis - A systematic review.

PURPOSE: The clinical utility of EEG in cases of NMDA encephalitis is broad with many findings indicating not just epileptiform activity but also encephalopathy and potentially providing insights into pathophysiologic mechanisms of disease. We aimed to determine the frequency of different abnormalities described on EEG and their association with outcome in patients affected by NMDARE through a systematic review of all cases published. METHOD: A systematic literature review of PubMed and Embase of all published cases of anti-NMDA receptor encephalitis with EEG results, was performed from inception to January 2018. RESULTS: A total of 446 cases of anti-NMDA receptor encephalitis with reported EEG findings were identified. 373 EEGs were abnormal, and this strongly correlated with ICU admission and time to recovery (p = 0.014 and 0.04 respectively). ICU admission and recovery were also correlated with delta range abnormalities including extreme delta brush (p = 0.007 and 0.03). Electrographic seizures correlated strongly with clinical seizures (p < 0.0001), however only 39 cases had EEG seizures captured, while there were 294 cases with clinical seizures. CONCLUSIONS: EEG is useful in the clinical management and prognostication of cases on NMDA encephalitis. This is particularly true of certain findings which portend a higher likelihood of ICU admission or poorer outcome and this may assist in the decision to pursue more aggressive treatment options.

A case of immune-mediated encephalitis related to daclizumab therapy.

This report will detail a case of immune-mediated encephalitis in the context of daclizumab therapy. Daclizumab is a humanised monoclonal antibody which, prior to its recent worldwide withdrawal due to safety concerns, was utilised as a disease-modifying therapy in relapsing-remitting multiple sclerosis. The withdrawal of this therapy was prompted by concerns over 12 cases of serious immune-mediated adverse reactions in the central nervous system. We report an additional case, including clinical data and results of neuroimaging, cerebrospinal fluid (CSF) examination and brain biopsy.

Electroconvulsive therapy for anti-N-methyl-d-aspartate (NMDA) receptor encephalitis: A systematic review of cases.

BACKGROUND: Anti-NMDA receptor encephalitis most commonly presents with psychiatric symptoms such as behavioural disturbance, catatonia and psychosis. Although the primary treatment is with immunomodulatory therapy, psychiatric symptoms often require adjuvant management. Side effects and treatment resistance limits the use of psychotropics, but the role of ECT has been minimally reviewed. OBJECTIVE: To review the safety and effectiveness of ECT for treatment of psychiatric symptoms in anti-NMDA receptor encephalitis. METHODS: A systematic literature review of PubMed, Embase and PsycInfo was performed from inception to June 2018. RESULTS: There were 30 cases of ECT used in anti-NMDA receptor encephalitis. Cases were typically young (mean age 27.7 years, SD 15.2) females (73.3%) with catatonia (86.7%). There was improvement of these symptoms in 65.2% of cases, interestingly without immunomodulatory therapy in 17.4%. ECT proceeded without complication in 86.7% of cases, with four cases prematurely ceasing ECT with further encephalitic deterioration. There were no anaesthetic complications. CONCLUSIONS: ECT appears to be an effective and safe adjuvant treatment in anti-NMDA receptor encephalitis, particularly for catatonia.

Delusions in Parkinson's Disease: A Systematic Review of Published Cases.

Delusions in Parkinson's disease (PD) are thought to be associated with disease progression and cognitive impairment. However, this symptom description is not consistent in the literature and there is a suggestion that different subgroups of psychotic patients occur in PD, which we aimed to clarify. Case reports were identified through a systematic search of databases (PUBMED, EMBASE, PsychInfo). Cases with isolated delusions were compared to those with both delusions and hallucinations. We identified 184 cases of delusions in PD. Delusions were primarily paranoid in nature (83%) and isolated in 50%. Those with isolated delusions had an earlier onset of PD (46 years vs 55 years), higher rates of impulse control disorders (40.2 vs 10.3%), dopamine dysregulation (29.9 vs 11.3%) and lower rates of cognitive impairment (8.0 vs 26.8%). There is unexpected heterogeneity amongst cases of delusional psychosis, that cannot adequately be explained by existing models of PD psychosis.