Prof K Ray Chaudhuri

Acute Psychosis in Parkinson’s Disease : Pre and Post Covid

Causes of psychosis and psychotic symptoms

Secondary Psychosis or Symptoms

• Sensory Sensory loss or deprivation

• Arousal state Entering/leaving sleep state; sleep deprivation

• Stress Extreme emotional stress, food/water deprivation, bereavement

• Acute infection Delirium, fever

• Intoxication and CNS agents Psychoactive effects of drugs; exogenous/endogenous toxins; toxic delerium

• Medical conditions Neurodegenerative disease; epilepsy; endocrine disorder; metabolic disorder; autoimmune disorder

And wait, there’s more...

Overactivation of downstream glutamate signaling to the Ventral Tegmental Area may

result in excess dopamine in the ventral striatum via the mesolimbic pathway

2017

Delirium

76 year old man Living alone with PD Levodopa COMT I Amantadine Poor self care Presented : Confused Incoherent “catching fish and flies” Aggressive Restless

Severe constiption Severe dehydration Low grade temperature UTI

Delirium – Clinical Presentation in PD

https://oncohemakey.com/delirium-6/

• Reported duration of delirium in PD: from 24 hours or less to under 30 days. Delirium was associated with prolonged hospital stay compared to PD patients without delirium.

Lawson et al. Parkinsonism and Related Disorders (2018)

et al

Is PD a risk factor for delirium?

Patient was on Pergolide Stopped suddenly for fear of valvulopathy Also had swollen red limb with burning pain Presents with high fever, confusion, hallucinations Recovery with supportive treatment but progressive worsening of Parkinsonian state

Delirium – Outcome in PD

DeMuro et al. Delirium. Chapter 1.

(2014)

DRUGS TO AVOID

Hellish Holidays

A Case:

• Stable PD on levodopa, rasagiline and comt inhibtors

• Long distance travel to sri lanka for holiday

• On arrival: • Acutely confused • Severely bradykinetic • Hallucinating • Hospitalised • Unable to swallow

Aggressive Rehydration Adjust medication time Soluble levodopa ? TD patch use Short term hypnotic

2011

PD for 15 years Living with partner Acutely admitted Severe self neglect Convinced about infidelity of spouse Aggressive and physically threatening

Pimavanserin (5-HT2A ) inverse agonist

Psychosis improved at 6 weeks / no motor worsening: Cummings et al. 2014

• First real-life case series of PD patients with COVID-19

• Older PD patients with comorbidity and possibly those on advanced therapies should be recognised as

a high-risk group (mortality rate of 50% among our 4 patients on advanced treatments)

• Motor and non-motor features, such as anxiety, fatigue, orthostatic hypotension, cognitive

impairment, and psychosis, worsened during the infection

• Need for setting a roadmap for health care professionals to the specific needs and therapeutic

decisions required to personalise management

May 2020 2020

Age > 75 years Advanced therapies (IJLI+DBS) Severe fatigue Anxiety Increasing LED requirement Hallucinations and Delirium Mortality

Mov Disord 2021

Fatigue Cognitive disturbances Pain Insomnia Anxiety

Spectrum of effects according to the triad of common clinical features in serotonin syndrome

The Hunter serotonin toxicity criteria – flowchart to guide clinical confirmation of diagnosis

Buckley N.A., Dawson A.H., Isbister G.K. Serotonin syndrome. BMJ. 2014;348:g1626.

Management

• Stop offending drug

• intensive care

• Active cooling

*Little evidence for anti-serotonergic drugs

Acute Psychosis and PD

• Pre Covid

• Severe stress • Acute Infection (UTI/RTI) • Acute Trauma • Drug interaction (Serotonin syndrome) • Drug withdrawal (DAWS, Infusion discontinuation) • Long distance high altitude flying • Dehydration • Procedural : DBS/IJLI/Apomorphine • Non Motor Fluctuation: Hypomania/Mania/Anxiety/Pain

• Post Covid

• Lockdown anxiety • Covid infection

• High viral load • Older age and comorbidites • Infusion therapies

Clinical and Research Team • Prof K Ray Chaudhuri, Director

• Dr D van Wamelen, Post-doc Clinical Research Fellow

• Dr V Metta, Consultant Researcher

• Dr V Leta, Clinical Research Fellow

• Dr K Rukavina Clinical Research Fellow

• Dr N Dimitrov, Clinical Fellow

• Dr P Reddy, Consultant Liaison

• Dr YM Wan, Clinical PhD Fellow

• Dr D Urso Clinical Research Fellow

• Dr Lucia Batzu Clinical Research Fellow

• Dr S Rota Clinical Research Fellow

• Dr A Sauerbier, Post Doc Clinical Research Fellow

Statistical and Data Support Prof P Martinez-Martin and team (Madrid)

King’s Stereotactic Surgery Group • Mr K Ashkan

• Dr M Samuel

• Dr R Saha

Research Management

• Ms A Rizos, EUROPAR European Manager

• Mr D Trivedi, Research Coordinator

• Ms A Podlewska, Research Coordinator and PhD Fellow

• Ms Juliet Staunton Research Coordinator

Nurse-led COE Research Programme

Miriam Parry, PD Nurse Specialist

Jenny Natividad PD NS

Virtual Technology Team Lead

Dr Dhaval Trivedi

Animal Model Team Lead

Prof Peter Jenner

King’s PAR-COG Group

Prof Dag Aarsland

King’s Parkinson’s Centre of Excellence Research Team

SPECIAL THANKS Dr Yi Min Wan Dr Silvia Rota