1. With thanks to Dr Paul Goldsmith (RVI, Newcastle) Dr Neil Archibald (JCUH Middlesbrough) & Dr Belinda Lennox (Oxford) for development & review January 2016 Screening in First episode Psychosis

2. Physical Screening for psychosis Only guidelines seem to be for pre-prescribing Since 2008 no recommendations re neuroimaging National Audit of Schizophrenia consistently reports appalling monitoring and interventions of basic physical parameters

3. Crawford et al Dec 2014 BMI in 51.1% Blood sugar intervention 53.5% Dyslipidaemia intervention 19.9%

4. New disorders antibody mediated encephalitis Voltage Gated Potassium Channel complex (LGI1, CASPR2, contactin-2) 2001 N-Methyl-D-aspartate receptor (NMDA) 2007 GABA-B 2008 AMPA receptor 2009 Glycine receptor 2012 D2 receptor 2013 GABA-A receptor 2014

5. NMDA encephalitis first reported 2007 Psychiatric prodrome seizures rhythmic movement disorder dysautonomia Coma Ovarian teratoma Dalmau J, Tuzun E, Wu HY, et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007;61:25–36

6. NMDAr AND PSYCHOSIS Ketamine can cause hallucinosis NMDAr hypofunction related to psychosis Glutamate xs implicated in psychosis NMDAr functioning related to trauma NMDAr functioning affects hippocampus and learning NMDA Receptors and Metaplasticity: Mechanisms and Possible Roles in Neuropsychiatric Disorders. Zorumski and Izumi. Neurosci Biobehav Rev. 2012 March ; 36(3): 989–1000.

7. Autoimmunity and Psychosis 6.3% prospective cohort 1 st episode +ve NMDAr antibodies 9.9% acutely ill psychosis 7% of refractory psychosis patients Zandi et al J Neurol 2011;258:686-8 Steiner et al JAMA Psychiatry 2013 ;70: 271-8 Beck et al BJ Psych 2015; 206: 164-165

8. Core clinical features of NMDAR-Ab encephalitis encephalopathy psychiatric symptoms cognitive symptoms seizures extrapyramidal movement disorder Autonomic instability CAN ONLY BE ONE FEATURE!

9. DIAGNOSIS – Auto-immune Clinical features plus EEG – slow waves Autoantibodies – eg NMDA MRI – high signal medial temporal lobes

10. Red Flags sudden-onset paranoid psychosis or rapid deterioration prodromal headache or raised temperature prior to onset cognitive impairment/delirium (short-term memory, disorientation) catatonia, particularly orofacial dyskinesia seizures, particularly faciobrachial seizures

11. Red Flags Changed sleep pattern autonomic disturbance e.g. hypo-/hyperthermia, unstable blood pressure, raised respiratory rate, tachycardia Suspected neuroleptic malignant syndrome Hyponatraemia (an indicator of anti-VGKC complex (LGI1) antibody encephalitis)

12. Aetiology Inflammatory process affecting BBB integrity Classic is Ovarian teratoma (brain tissue!) Paraneoplastic – Ca Lung, ovaries, testis, thymus, Uterus, Colon and Larynx. Post viral (?related to intra-uterine exposure)

13. Investigations for everyone U+Es (eGFR) – watch for low Sodium LFTs (gamma GT) TFTs Prolactin – if raised then gonadal hormones FBC Inflammatory screen - CRP and ESR Random Blood glucose ECG Urine screening for cannabinoids

14. If Psychosis plus Red Flags EEG MRI Autoantibodies (Anti neuronal Anti-VGKC-complex and anti-NMDA receptor)

15. Neurology referral Seizures plus psychosis Positive screening plus psychosis Seek advice if negative screening but still red flags N.B. if patient has a typical presentation – neurology often treat before the antibodies are back!

16. Treat with assertive immunotherapy when: psychosis plus: any other features of encephalopathy (reduced consciousness level, seizures, autonomic instability, catatonia) or investigations to support encephalitis (abnormality in EEG, MRI or CSF) Advances in psychiatric treatment (2014), vol. 20, 92–100

17. 1 st Episode Psychosis Screening and Guide for Neurology Referral 1 st Episode Psychosis Pathway Version 1.0 June 2015 Neurology Auto Immune Encephalitis Seizures and Psychosis  Neurology Referral Core Clinical Features: Seizures Encephalopathy Psychiatric symptoms Cognitive symptoms Movement disorder Autonomic instability Investigations for all: U&Es & EGFR TFTs Prolactin (if raised then Gonadal hormones) LFTs FBC Random Blood Glucose ECG Urine drug screening Inflammatory markers eg CRP First Day Best Average time in days Red Flags: Sudden onset psychosis Rapid deterioration in functioning Prodromal headache or fever Delirium or cognitive impairment Movement disorder e.g. facial dyskinesia Seizures (particularly faciobrachial seizures) Changed sleep pattern Autonomic disturbance (temp/BP/pulse/resp rate/fluctuations) Suspected NMS Red flags + Psychosis  Investigations: EEG MRI Autoantibodies (antineuronal, an17ti-VGKC and anti- NMDA)., Negative screening and no clinical improvement  Neurology advice If positive results  neurology referral 3 weeks Consider referral if multiple red flags before screening back

18. Summary by a neurologist Although it seems likely that the majority of patients presenting with first episode psychosis will not have an autoimmune encephalitis, the algorithm is simple and the cost of missing the diagnosis is tremendously high. Neurology and psychiatry are comfortable bedfellows every else in the world but the UK. Models and opportunities for closer working can only be a good thing. Regardless of aetiology, these are patients with abnormal brain function, after all.