ASSOCIATION OF BRITISH NEUROLOGISTSACUTE NEUROLOGY BOOTCAMP 2020

Wednesday 10 June 2020

Dr Kuven Moodley, St George’s Hospital

Delirium and Coma

DISCLOSURES

• I have no actual or potential conflict of interest in relation to this presentation

OUTLINE

• Coma in the ED

• Coma caveats for ITU

• Pitfalls in coma prognostication

• Acute confusion, delirium and encephalopathy

• Cases

COMA IN THE EMERGENCY DEPARTMENT

• Recognise coma i.e. coma or coma-mimic?

• Is the pathology brainstem or cortical? This is answered clinically

• Empiric management principles

• Is the pathology structural? This is answered with neuro-imaging

• Make an estimate of the cause/causes of coma

• Specific management principles

e.g. hypertensive encephalopathy, subarachnoid haemorrhage, encephalitis

COMA: DEFINITION (≠ GCS OF 7 OR LESS)

• A state of unawareness of one’s self and one’s environment

• … in which the affected individual is completely unresponsive

• … and from which the individual cannot be aroused

• Lack of purposeful responses to external stimuli (visual, auditory, tactile)

• Eyes do not open (or close) in response to stimuli

• Remember: brainstem reflexes and posturing movements are not purposeful

CAUSES OF GCS < 8

• Coma from any cause

• Stroke: locked in syndrome, bilateral/multi-focal simultaneous/consecutive strokes

• Encephalopathy/ delirium

• Severe neuromuscular weakness

• Hypersomnolent stupor

•Akinetic-mutism

• Agrypnia excitata/ status dissociatus

• Catatonia

• Psychogenic coma

• Malingering

THE SURGICAL SOLUTION

THE FOUR SCORE

• Coma with focal signs

-Structural (ICH, SOL, CVA, TBI…)

-Neuro-infection/-inflammation

- Ictal/ post-ictal

• Coma without focal signs

- Toxic-metabolic

- Endocrine

-Organ failure

(Wijdicks et al., 2005).

A SUGGESTED APPROACH

• Is it a coma?

• Are there focal signs?

• Is there meningism?

• Observe (posturing, signs of external injury, pattern of breathing, vital signs)

• GCS

• Eyes: gaze conjugate/deconjugate, gaze deviation, eye movements

• Pupils: size and responses (bright light, dark room, may need magnifying glass)

• Oculo-cephalic reflexes, Optic discs

• Motor function: motor responses, DTRs, tone, plantar responses

PUPILS

PUPILS

Pinpoint

• Bilateral: drugs, hypercapnia, pontine pathology

• Drugs: narcotics, phenothiazines, barbiturates, clonidine, organophosphates (note: ITU meds)

•Unilateral: lateral medullary syndrome, hypothalamic injury

Dilated

• Bilateral: cerebral hypoxia, drugs and toxins

• Drugs: LSD, cocaine, anticholinergics, diphenhydramine, NE infusion, hyperMg2+, aminoglycoside toxicity

• Unilateral: CNIII (may be false-localising), eye drops, ‘nebulised’ eye

BREATHING

OCRS (MEDIAL MIDBRAIN AND PONTINE FUNCTION)

FALSE-LOCALIZING SIGNS

• Acute shift > 1cm

• Subfalcine (ACA)

• Transtentorial

• Kernohan’s notch

Ipsilateral weakness

Contralateral HH (PCA)

•Cerebellar

SPONTANEOUS EYE MOVEMENTS IN COMA I.E. NON-PURPOSEFUL

• Ocular bobbing (pons)

• Inverse bobbing (diffuse cerebral)

• Windshield wiper eyes (CN3 lesions)

• Ping-pong gaze (metabolic/bicortical)

Roving EMs: are horizontal by definition and are a marker of intact brainstem function.

PUTTING IT ALL TOGETHER WITH SOME MEDICINE

• Airway

• Breathing: rate, rhythm and depth. ABG if tachypnoea (hypoxia, gradient vs. acidosis vs. hyperventilation-hypocarbia) or hypopnoea (CO2, ? Cushing’s triad)

• Circulation: Remember Cushing’s triad, hypertension with blindness, dysautonomia

• Disability

Alert vs. lethargy

Obtundation: rouse to touch. Verbal responses usually slow, and incoherent

Stupor: rouse to pain. Verbal responses usually incomprehensible

Coma: not rousable. Remember to expose skin.

MEDICAL CAUSES OF IMPAIRED CONSCIOUSNESS

-Hypoglycaemia (<3.3 mmol/L)*

-Hypertension

-Hyperglycaemia (hyperosmolar)

-Hypoxia/stroke

-HIV + infections + post-infectious

-Hypovitaminosis (Thiamine*)

-HAGMA (causes of)

-Hyponatraemia (<120 mmol/L)

Toxins and Medication

Trauma (#-Fat embolism)

Hypercarbia (acute)

Hypercalcaemia (>2.80mmol/L)

(Hyper)Uraemia (>20mmol/L)

Hypothyroidism

Hyperammonaemia (>50 fasted)

COMA IN THE ED

• Review the patient. Look at BM, blood gas and CT scan in-person

• If severe metabolic acidosis (pH < 7.3), check AG, serum osmolality, ? osmolar gap.

HAGMA:

Lactic acidosis (remember Type A and Type B)

Uraemia, DKA/AKA

CO/Salicylates/Theophylline/Ethanol/Iron/INH/Ethyl glycol/glue/cyanide etc

D-lactic acidosis (short bowel syndrome, propylene glycol)

MRI/LP/EEG is not needed in all cases

Take ownership of the patient, even if you think its ‘medical’

MANAGEMENT: EMPIRIC MEASURES

Protect airway

If BM low, give glucose and thiamine

If pupils pinpoint, give trial of naloxone

If CT is surgical, consider hyperosmolar therapy (0.5-1g of mannitol)

If vasogenic oedema, consider steroids

Maintain head-up (30-40 degrees) if possible

Treat seizures and fever aggressively

Maintain euglycaemia

A STRUCTURED APPROACH IS NEEDED

Acute Sub-acute

Vascular Multi-infarct, Strategic infarct

ICH (including RVCS-related)

Angiitis: primary, toxic, infectious

PRES/eclampsia

Hyperviscosity syndromes

Angiitis, ventriculitis, other vasculopathies

ICH (including CVST-related)

Intravascular lymphoma

PRES/eclampsia

Hyperviscosity syndromes

Infectious HSV, HZV, enterovirus etc. HIV, PML, SSPE etc.

Toxic-Metabolic Hypoxia

Wernicke’s (3%)

Toxins

Porphyria

Any of the causes of asterixis

Vitamin deficiencies (B6, B12)

Osmotic demyelination

Mitochondrial disease decompensation

Auto-immune Cell mediated e.g. ADEM

Antibody-mediated e.g. anti-NMDA ab, anti-AMPAR ab

Cell mediated e.g. Sarcoid

Antibody-mediated e.g. anti-VGKC-Ab,

Anti-TPO Ab

Metastases and Cancer Metastases Infiltrating tumours

Lymphoma

Pseudotumour e.g. CNS castelman’s

Iatrogenic Medications

Exposure vs. withdrawal

Polypharmacy + clearance

Medications

Neurodegenerative

Seizures/Episodic Symptomatic seizures vs epilepsy

Familial hemiplegic migraine (CACNA1A)

Psychiatric

RECAP

• Is the BM normal

• Coma or not

• If Coma, can you determine if cortical or brainstem

• Is it structural, ischaemic or toxic-metabolic

• What empiric therapies are needed?

e.g. antivirals, antibiotics, anti-epileptics, thiamine…… Bateman, 2001

CASE 1

•50-60M

•Auto-immune pancreatitis, malabsorption

•Abdominal pain, vomiting: anti-emetic + opiate

•Sweaty, tachycardia

•BM: 3.3 mmol/l - given dextrose

•PTWR: ‘looks drunk’, ‘sleepy’, disorientated to place

•Neuro r/v (14:00; referred at 09:30)

•E2M4V3, stupor

•PEARL (3, sluggish)

•Nystagmus, dysarthric, cold + sweaty

WERNICKE’S ENCEPHALOPATHY

Alcohol, chronic malnutrition, bariatric surgery, recurrent hypoglycaemia, rapid weight loss, anorexia , Hyperemesis gravidarum, frailty, post-chemo, peritoneal dialysis, chronic magnesium deficiencies, refeeding

Classic triad: confusion, ataxia, ophthalmoplegia. 10% have all three features

15% have none of the triad

Other features: nystagmus, miosis, sluggish pupillary responses, optic neuropathy, vestibulocochlear impairment, hypothermia, autonomic instability, changes in behaviour (apathy psychosis)

Equivalent of 500mg iv tds for 5 days if diagnosis suspected. Prevention is better than cure

CASE 2

70-80F.

Last seen normal at dentist

Seen neighbour some six hours later – collapsed in garden

Stroke call

E1V4M2. Varying motor responses to pain

No response to commands/ pantomime/ visual threat

Anisocoria R5/L3, right non-reactive

Moving all four limbs, non-purposeful.

NIHSS 20-22

BP: 200/140. P: 70bpm, regular. BM: 4.2mmol/L. Afebrile.

CT/A: normal

DW-MRI @ c20 hours post-onset

Simultaneous thalamic infarction

CASE 3

50M, fit and well

2 days of fatigue, fugue, headache, then vomiting

Intractable vomiting in ED, then seizures

Intubated at E2M4V1

Normal CT

You are asked to see him

You do – there is not much to find!

What next?

ABG (FIO2 0.4) – ON ARRIVAL, BEFORE CONVULSIVE SEIZURES

pH: 7.465

PaCO2: 2.8 kPa/ PaO2: 18.7 kPa

HCO3: 14.2 mmol/l

BE: -0.6

Lactate: 9.5 mmol/L

FIRST LINE TESTS

Bloods: normal

LP: normal

Review of CT: maybe swelling

FORMULATION

-Acute encephalopathy, pre-coma, medically-induced coma

-Cerebral oedema associated with acute HAGMA

-EEG, on sedation hold, identified triphasic waves

Metabolic: liver failure, renal failure, hyperammonaemia

Anoxic brain injury

Endocrine: Hashimoto’s, hypercalcaemia

Undisclosed poisoning (Lithium, Naproxen, SSRI-serotonin syndrome)

Infective

CASE FOUR

22F, Day 7 post caesarean (breech presentation), otherwise well in pregnancy

Presented to ED with headache, confusion, vomiting and blurred vision

BP: 160/90 (around 100/60 during last trimester). BM 6.3 mmol/l

Generalised convulsive seizures in ED – settled with Lorazepam

Post-seizure: GCS E2M3V2, pupils dilated but reactive.

No improvement over next 30mins. Further seizures- intubated

CT normal. Treated with magnesium, acyclovir and Keppra.

FORMULATION

22F, with hypertension and encephalopathy progressing to seizures. Postpartum

PRES/ Hypertensive encephalopathy

Central venous sinus thrombosis

Eclampsia of post-partum onset

Viral Encephalitis

CASE FIVE

36F

Health care assistant

ED: ‘acute psychosis’

Hearing voices, thought insertion, agitated, combative

Hypervigilant. Pressured, perseverative speech

Paranoid. Tangential

Temp: 37.7; P: 90; BP: 140/90; sweating

Pupils dilated but reactive

Symmetric spontaneous, non-purposeful movements

CASE FIVE

Bloods/CT head normal

Admitted to psychiatry

Transferred to medicine: drowsy, unable to easily rouse

E2M4V1, PEARL, conjugate gaze, OCRs intact

No meningism

Temp: 37.7/ Pulse: 100/ BP: 140 over 80/ RR: 8, irregular and shallow

Intubated: ? Central apnoea, GCS concerns, started on anti-virals

CASE FIVE: MRI

ANTI-NMDAR AB-MEDIATED ENCEPHALITIS

S1: (70%): ‘flu-like’ prodrome +/- fever (days-weeks)

S2: Acute psychosis + decline in episodic memory, verbal fluency

S3: Akinetic-mute/catatonic; hypoventilation/dysautonomia

S4: dyskinesia, dystonia and choreo-athetoid movements

S5: slow recovery if treated

> 80%: ITU support: autonomic instability and apnoea

But… spontaneously remitting + incomplete forms

LIMBIC ENCEPHALITIS (LE)

Classic limbic encephalitis:

subacute episodic memory loss accompanied by disorientation, depression, irritability and seizures

In addition: agitation, sleep Δ’s, autonomic arousal, hallucinations

Histologically: medial temporal lobe inflammation

MRI: T2 + FLAIR Δ’s: MTLs and/or hippocampi (>90%)

Infective: HSV, VZV, HHV6 (renal transplants), others

Paraneoplastic (PLE)

Auto-immune (AILE)

AUTO-IMMUNE LIMBIC ENCEPHALITIS

1970-2000

• Paraneoplastic: neurological syndrome can precede tumour detection by 3 years

• Antibody (Ab) to intracellular antigens e.g. Anti-Hu Ab in Lung Cancer

• Poorly responsive to treatment even with removal of tumour

2000

• First report (2 patients) fully reversible steroid-responsive LE

• Patients with episodic memory loss and refractory seizure disorders

• Ab to VGKC Ab (cell surface receptor)- titres correlate to disease

2005

• Other Steroid-responsive LE reported- VGKC Ab negative, thyroid Ab negative

• Acute neuropsychiatric presentations

• 2007: Ab to NMDA receptor (a synaptic protein)

It is increasingly recognised that the antibody-mediated

diseases can affect extra-medial temporal structures.

There are no rules!

SCOPE OF THE PROBLEM

England: 4% of all ITU encephalitis admissions

California Encephalitis project: est. 1998 NMDAR Ab – most common single cause of encephalitis

65 % of paediatric cases

66% of all patients with psychotic features

10% of previously undiagnosed cases

Take home: NMDAR Ab is a first line test for encephalitis. Send it with viral PCR, early!

Depressed vs agitated phenotypes

PNS: CELL-SURFACE ANTIGENSCNS synaptic Ab Syndrome Tumour Tumour frequency

VGKC Ab

LGI 1

Classic LE, hyponatraemia (60%),

faciobrachial dystonic seizures (40%)

Thymus, Lung < 20%

VGKC Ab

CASPR2

Neuromyotonia, LE

(higher relapse rates)

Thymus < 20%

NMDAR Ab Psychiatric, seizures, dyskinesia,

autonomic

Ovarian teratoma < 18 y.o: 10%

>/= 18 y.o: 50-60%

AMPAR Ab Classic LE, mania, atypical psychosis Lung, Breast, Thymus 70%

GABAbR Ab Seizures (almost all), Paranoid

Schizophrenia

SCLC 60%

GlyR Ab Encephalomyelitis with muscle

spasms, rigidity, myoclonus,

hyperekplexia

Rare

mGluR5 Ab Limbic Encephalitis

Orphelia syndrome

Hodgkin’s Lymphoma 100%

CASE SIX

• 60-70M

• D&D referral.

• Admitted from clinic with suspected Ca penis (mass + pain + discharge)

• Seemed ‘okay’ at the time, history of anxiety (no Rx)

• Changed during admission. Rx for secondary infection of fungating mass (quinolones)

• Changes in behaviour at some point. Escalated quickly.

• Behaviour an ongoing issue despite CRP/fever settling.

• Unable to advance care

CASE SIX

IP Psych review

Undisclosed et-OH use (started on thiamine)

Childhood abuse, anxieties about being examined

Later, delusional ideas (persecutory) + irritability

IP Pain team review

Opiates + escalation (gabapentin, amitriptyline, buprenorphine, lorazepam)

Increasingly agitated, restless on ward. Haloperidol prn.

Violent episode, with staff injury, prior to review

E3M5V3. Myoclonus. Sluggish, small pupils. No asymmetry otherwise

DELIRIUM (PAIN-RELATED) AND MYOCLONUS (IATROGENIC)

• 3/12 of pain. Local pain (burning-aching) with tactile hypersensitivity

• Burning worsens during day, then less aware of nocturnal events

• BNO (days)

• Clear collateral of fluctuating behavioural changes, associated with disorientation

• Local anaesthetic. Increased mirtazapine. High dose thiamine. Reduce Gabapentin.

• Switched to prn sedation policy.

• NB of timing of pain meds emphasized (team advised to tally and switch to patch)

• Laxatives

• Improved and surgery performed without need for IMCA etc.

CASE SEVEN

• 67 M, T2DM (2 years, no end-organ damage)

• B12 deficiency ffg. Previous gastrectomy (B12 normal now)

• Several medical admissions for ‘confusion’ attributed to UTI.

• Deep sleep Irritable, tremulous, slurred speech. Asterixis. E2M4V2 (worse)

• Urine: pyuria. No growth (>5 occasions)

• Family demand neurology review……

• NH4+ 74 mmol/L; LFTs+INR negative

DELIRIUM/COMA SPECIAL CASES

• small bowel bacterial overgrowth syndrome

• pancreatic encephalopathy

• fat embolism syndrome in the context of fractures/pancreatitis/ burns

• Uraemic encephalopathy

DELIRIUM: DEFINITIONS + HISTORY

• deliriare: “to go off the furrow”

• DSM IV:

• “an acute, fluctuating disturbance of consciousness with impairment of attention and cognition that results from a medical condition”

• Introduced in DSM III (1980)

• Acute confusional state, encephalopathy, acute brain failure, ICU psychosis….

Hypoactive --- Hyperactive

DELIRIUM (DSM-5 VS DSM-IV)

NUMBERS + EVIDENCE

20% of acute, old-age admissions.

Arises as a complication in 10% of all acute medical admissions

Frequent complication of surgery (15-50%; higher in neurosurgery and orthopaedic surgery)

Frequent complication of ITU admission (70-90%)

Associated with increased mortality, morbidity and institutionalisation

Cole MG et al. Systematic detection and multidisciplinary care of delirium in older medical inpatients: a randomized trial. CMAJ 2002;167(7):753-9

Cole MG et al. Delirium: prevention, treatment, and outcome studies. J Geriatr Psychiatry Neurol1998;11:126-37

Prevention is definitely better than cure

NICE Quality standard: You are obliged to screen, assess and implement prevention plans

Up to 30% of cases are preventable

THE SOCIO-ECONOMIC IMPACT…

Beyond acute:

- 4 in 5 delirium patients

have ongoing cognitive

symptoms at three months

Sheehan et al. 2013

- 60-70% of inpatients

with delirium have

concurrent dementia

Morandi et al. 2011

Mortality

Falls

Dementia

Institutionalization

Death

Delirium is hardly mentioned in

UK National Dementia Strategy.

It is under-recognized

SEVERAL SCREENING TOOLS

• CAM

• 4AT

• Confusion rating scale

• Delirium index

• Single Question in Delirium

• Bedside Confusion Screen

• Screen everyone or those with Risks only? Early diagnosis vs. increased care utilization

Screening of all adult patients

is meant to occur at the point

of entry to hospital

Ideally, within 2 hours in ED, or

within 24 hours of hospital

admission

TOXIC ENCEPHALOPATHY: SPECTRUM

• Delirium: waxing-waning consciousness, spatiotemporal disorientation, impaired vigilance (+/-fear, anxiety, hallucinations, altered sleep/wake).

• Obtundation: drowsy but rousable (differentiate from apathetic delirium)

• Stupor: Repeated, rigorous stimuli to need to rouse patient.

• Coma from toxin/ metabolic effects of toxin/metabolites

• Organic psychosis: impaired reality monitoring, disorganised thinking (differentiate from agitated delirium)

• Coma for therapeutic purposes

CONCLUSION

Causes of delirium, encephalopathy are interchangeable

Coma can be downstream to both

Coma has a differential… there is much to read

Having an organised clinical approach is more important than agonising over (perceived gaps) in knowledge

Common things are common

Empiric treatment must cover the common

Urgency is in the eye of the beholder!

Front Hum Neurosci. 2015; 9: 105.

FAILURE TO WAKE ON ITU

RICHMOND AGITATION-SEDATION SCALE (RASS)

YOU MUST SEDATION HOLD TO PROGNOSTICATE

ASSOCIATION OF BRITISH NEUROLOGISTSACUTE NEUROLOGY BOOT CAMP 2020

Week 1

08 June 7 – 7.15pm

7.15 - 8pm

Imposter syndrome & ‘The Bag’ – Dr Richard Rees, London

Headache – Dr Barney Fiddes, Cambridge

09 June 7 – 8 pm Acute functional neurology – Dr Biba Stanton, London

10 June 7 – 8 pm Delirium & Coma – Dr Kuven Moodley, London

11 June 7 – 8 pm Seizures – Dr Ann Johnston, Cardiff

Association of British Neurologists, Ormond House, 27 Boswell Street, London WC1N 3JZ

Email: info@abn.org.uk. Telephone: 02074054060

Week 2

15 June 7 – 8 pm Stroke - Dr Akram Hosseini, Birmingham

16 June 7 – 8 pm The Dizzy Patient - Dr Diego Kaski, London

17 June 7 – 8 pm Acute neuromuscular weakness - Dr Aisling Carr, London

18 June 7 – 8 pm Surviving your first year as registrar - Dr Alex Foulkes, London