1. Investigating Psychosis R.J.Hackett

2. This presentation concerns: 1) investigation of acute psychoses that may arrive acutely on an adult or adolescent psychiatry ward or EIT and 2) investigation of chronic or recurring psychoses, often with negative symptoms. These are patients who one often takes over, but in whom you start to question the cause. I have not covered late-onset psychoses in patients with Parkinson’s disease or degenerative disorders.

3. Traditional Psychiatric Approach Psychiatric diagnoses are syndromes – symptoms that occur together. Underlying causes are not exhaustively sought. Treatments are symptomatic. Psychological theories of cause are widely held.

4. Neurological Approach Underlying medical causes of syndromes are always investigated. Extensive search for pathological cause. Extensive use of medical tests. Where possible treatment directed at underlying cause.

5. Schizophrenia A syndrome of positive psychotic symptoms: Auditory hallucinations (often) Delusions Patient often lacks insight (this can change with treatment). With or without negative symptoms (apathy, blunt affect, poverty of thought).

6. Considerations in Investigations Cost of the test? Yield? Cost of failing to identify treatable cause? How common are the treatable causes?

7. Current standard admission work up for new psychosis Urine for drugs. FBC, biochemistry, LFT, Thyroid, bone profile. Vitamin B12, serum folate (a recognised co- factor in psychosis).

8. Infective causes HIV Neurosyphilis

9. Recognised causes of syndrome of schizophrenia Toxic causes: recreational Autoimmune brain disease (5-10%?). Medication. Metabolic disorders. Infection. NB. Structural brain lesions (tumour, trauma, stroke, MS plaque) very rarely cause psychosis.

10. Examination Full neurological examination. History must include medications. Brief test of anterograde memory. History of stable learning difficulty or of cognitive decline. Mental state examine for catatonic features.

11. Toxic Causes Recreational drugs: Urine drug screen. Cannabis Amphetamine Cocaine Psilocybin (august to 1 st frost)

12. Autoimmune causes Features to look out for: Impaired recall for onset/admission. Impaired anterograde memory. Facial dyskinesia. Catatonic symptoms. Personal/family history autoimmune disease. Note autoimmune causes can (often) be present without any of these features.

13. Autoimmune causes NMDA receptor antibodies. Voltage gated potassium channel antibodies. Anti GAD antibodies. Hashimoto’s encephalopathy (anti-thyroid peroxidase antibodies) SLE.

14. Further evidence for CNS inflammation in psychosis can be obtained from: CSF – oligoclonal bands, lymphocytosis. MR brain – high signal on FLAIR sequences.

15. Infective causes HIV Neurosyphilis

16. Special situations Psychosis immediately after childbirth and other physiological stresses. Often accompanied by confusion. Consider urea cycle disorders (plasma ammonia↑, urinary orotic acid, plasma urea↓)

17. Special situations Psychosis accompanying epilepsy Post-ictal psychosis (history typical, no available test If ictal or interictal consider: Porphyria (other metabolic causes usually associated with learning difficulties)

18. Limbic encephalitis full syndrome acute psychosis + amnesia + seizures. Usually middle age or older. Occult malignancy (most commonly lung) Other neurological deficits common (eg periferal neuropathy) Paraneoplastic antibody screen, imaging screen for malignancy.

19. Summary: investigations for acute psychosis Routine Bloods inc. B12, folate. Urine drug screen If negative Antibodies NMDA receptor/voltage gated K channel, GAD. Thyroid peroxidase antibodies, ANA. MR with flair sequences Plasma ammonia

20. Summary: investigation of acute psychosis HIV/syphilis serology – depends on risk factors. Consider CSF for oligoclonal bands.

21. Chronic psychosis – identifiable causes Consider metabolic disorders. Adult onset inborn errors of metabolism (IEM). Many of the lethal infantile IEMs can present in attenuated forms from adolescence until middle age. Psychosis (sometimes on its own) is common presentation.

22. Prevalence is unknown because they are never looked for. Rarely diagnosed ≠ Rare. i.e.probably many unidentified cases in psychiatric populations. Some are treatable.

23. Investigation of chronic psychosis Consider metabolic disorder if: Evidence of progressive cognitive decline. Ataxia. Movement disorder esp. dystonia (i.e. don’t just blame antipsychotics!). Spasticity.

24. Metabolic disorders to consider Nieman Pick disease type C Juvenile metachromatic leukodystrophy Adult-0nset Tay Sach disease. Fabry disease Alpha mannosidosis Cerebrotenindous xanthomatosis Adrenoleukodystrophy

25. Homocystinuria cystathionine beta synthase def. methylene tetrahydrofolate reductase def. Wilson’s disease.

26. Neiman Pick disease type C cognitive impairment, vertical gaze palsy, ataxia. Test: Oxysterols (blood)

27. Lysosomal storage disease Test: white cell enzymes Juvenile metachromatic leukodystrophy psychosis for years →spasticity, ataxia. Tay Sach’s disease. Ataxia, spasticity, LMN signs, dystonia. Fabry disease. painful neuropathy, young stroke. Alpha mannosidosis. pre-existing LD, ataxia, spastic, dysmorphic.

28. Test: very long chain fatty acids (blood) Adrenoleukodystrophy. spasticity, seizures Test: plasma cholestanol Cerebrotendinous xanthomatosis tendon xanthomas, cataract, spasticity, ataxia.

29. Test: plasma amino acids + urinary amino acids (homocysteinuria) + urinary organic acids. Cystathionine β synthase def. marfanoid, young stroke, ataxia. Methylenetetrahydrofolate reductase def. spasticity, young stroke, perif. Neuropathy.

30. Test: Plasma copper + caeruloplasmin Wilson’s disease

31. Summary: tests for chronic psychosis MR brain (for space occupying lesion or leukodystrophy) Oxysterols White cell enzymes Plasma amino acids Urinary amino acids Urinary organic acids Very long chain fatty acids Plasma cholastanol Serum copper + caeruloplasmin