ACUTE CONFUSION

Dr Apeksha Shah, Consultant Neurologist

11 th September 2020
Objectives

1. Neuroanatomy and physiology of

wakefulness and coma

2. A systematic approach to the confused

patient including diagnosis and
management
NEURONATOMY AND
PHYSIOLOGY OF
WAKEFULNESS AND
COMA
What is consciousness?
◦ Consciousness = wakefulness + awareness

◦ Wakefulness (or alertness) describes the level of consciousness

or arousal

◦ Awareness and thought make up the content of consciousness:

the perception of self and the surroundings. ‘The subjective
character of experience’ (Nagel).
 Wakefulness
Wakefulness/ Alertness maintained by the
ascending reticular activating system (upper
brainstem and thalamus), projecting to the
cerebral hemispheres
Cholinergic and monoaminergic pathways are
both active during wakefulness, and have
differing activity levels during REM and
NREM sleep

Curr Neuropharmacol. 2008 Dec; 6(4): 367–378;

adapted from Saper 2005, pg 1258
 Awareness
◦ Awareness/ thinking is dependent on large-
scale frontoparietal networks, encompassing
the multimodal association cortices, and
their thalamic connections
◦ Default mode network (or internal awareness
network) is involved in self-related processes
and ‘thinking’
◦ Central executive network (or external
awareness network) is involved in attention-
demanding cognitive tasks
By Nekovarova, Fajnerova, Horacek, Spaniel - Bridging disparate symptoms of schizophrenia: a triple
network dysfunction theory, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=62546913
Coma and confusion
◦ Coma/ Stupor/ Drowsiness = diminished level of consciousness

◦ Confusion = clouding of the content of consciousness: inability to

maintain a coherent sequence of thoughts, usually accompanied by
inattention and disorientation
 Coma and
confusion
◦ We will consider confusion and reduced
level of consciousness together, since they
are often correlated with each other, and
have the same causes
◦ These are caused by generalised or
widespread/multifocal brain processes
◦ NOT focal brain processes (with a few
notable exceptions)

Perri, Stender, Laureys and Gosseries. Functional Neuroanatomy of disorders of

consciousness. Epilepsy and Behaviour 2014;30:28-32
Pathophysiology of
confusion and coma
◦ Interruption of energy substrate delivery
◦ Hypoxia, ischaemia, hypotension
◦ Hypoglycaemia
◦ Alteration of the neurophysiological responses of neuronal membranes
◦ Drugs
◦ Alcohol intoxication
◦ Epilepsy
◦ Hypothermia
◦ Na, osmolarity, CO2, Ca, toxic endogenous metabolites (urea, NH3),
hyperglycaemia
◦ Hypertension
◦ Humoral disturbances
 Pathophysiology of
confusion and coma
◦ Aberrant stress responses
◦ Systemic infection (UTI, LRTI), systemic illness
e.g. cancer, post-surgery, ITU
◦ Exaggerated response to normal levels of stress
or inflammation, in patients with background of
vulnerable brain
◦ Abnormally intense stress or inflammatory
response (changes in HPA axis)

Maclullich, Alasdair M J et al. “Unravelling the pathophysiology of delirium: a focus on the role of
aberrant stress responses.” Journal of psychosomatic research vol. 65,3 (2008): 229-38.
doi:10.1016/j.jpsychores.2008.05.019
Pathophysiology of
confusion and coma
◦ Other direct brain injury
◦ Traumatic brain injury
◦ Note post-traumatic amnesia
◦ Intracranial haemorrhage
◦ Primary CNS infection/ inflammation
◦ Mass lesions with oedema
◦ Hydrocephalus
◦ Strategic discrete structural causes:
◦ Brainstem infarction/ haemorrhage
◦ [Right parietal stroke]
 SYSTEMATIC
APPROACH TO THE
CONFUSED PATIENT
Case KR
◦ 62yo right-handed woman
◦ Presented to A&E with vomiting and headache. Given paracetamol and metoclopramide, felt much better, and went
home with some more metoclopramide
◦ Over the following 2 weeks became increasingly sleepy
◦ Not eating much, not drinking, sleeping 23 hours per day
◦ No further reports of headache or vomiting. One recorded fever.

◦ PMHx: nil
◦ DHx: metoclopramide prn (recent)
◦ Lives with husband and son, works in a care home
It’s all in the history
◦ Collateral, collateral, collateral
◦ Predisposing factors?
◦ Elderly
◦ Underlying dementia (acute-on-chronic
confusion)
◦ Comorbidities

◦ Drug history
Case KR

◦ RR 20 br/min, Sats 95 % (OA), Temp 36.0 DegC, HR 76 bpm, BP 107/72 mmHg

◦ Drowsy but rousable. Responses very slow, orientated to person and place but not time. No focal
neurological signs.
◦ Bloods: Na 128mmol/l (NR 133-146), K 4.9 mmol/L, lymphopaenic, CRP 69, raised D-dimer, ferritin
and LDH
◦ Normal LFTs, TFTs, bone profile
◦ Normal CXR
◦ COVID PCR negative but Ab positive
What’s in a name?
◦ Acute confusional state
◦ Delirium
◦ Encephalopathy
◦ Acute brain injury
What’s in a name?
◦ Inattention and fluctuating course
◦ Altered arousal
◦ Disorganised thinking
◦ Disorientation
◦ Perceptual disturbances
◦ Psychosis
◦ Sleep-wake disturbance
Detecting delirium: Confusion Assessment
Method

Includes hypervigilance.

Adapted from Inouye et al, 1990, Annals of Internal Medicine

www.the4at.com
Differential diagnosis
◦ Chronic “confusion”/ cognitive impairment
◦ Get a collateral
◦ Some patients with dementia do fluctuate (esp DLB)

◦ Aphasia
◦ Should be no clouding of consciousness/ fluctuations/ agitation
◦ Acute stroke causing aphasia may show other left hemisphere signs,
or the story may be hyperacute
Causes of DELIRIUM
◦ Drugs
◦ Eyes or ears
◦ Low oxygen
◦ Infection
◦ Retention (urinary/ constipation)
◦ Ictal states
◦ Under-nutrition
◦ Metabolic
Causes of DELIRIUM
◦ Drugs
◦ Eyes or ears
◦ Low oxygen
◦ Infection
◦ Retention (urinary/ constipation)
◦ Ictal states
◦ Under-nutrition
◦ Metabolic
Case KR

◦ CT head showed appearances of an empty sella

◦ The medical team suspected that 2 weeks ago she had had pituitary apoplexy (to account for the
headache and vomiting), and treated her with hydrocortisone for suspected hypopituitarism.
◦ The differential diagnosis included viral encephalitis, so aciclovir was started
◦ CSF examination was delayed by 24 hours, but was normal
◦ Repeat tests showed new hyperglycaemia, with hyperosmolarity, and she was diagnosed with HHS
◦ She developed an AKI (which gradually improved on cessation of aciclovir).
Case KR

She continued to deteriorate and became more and more drowsy. Intermittent jerking and gaze deviation
was noted and she was started on anticonvulsants.
By day 6: E2V2M5
Regular symmetric myoclonic jerks of both upper limbs and peri-oral muscles
No clear dystonic posturing or other ictal movements
Pupils slightly dilated, symmetrical, reactive
Dysconjugate gaze – oculocephalic reflex preserved.
No clear facial asymmetry
Mildly increased tone all four limbs
Plantars down
Reflexes globally brisk, Hoffman's present bilaterally, symmetrical
Clinical signs in encephalopathic patients
◦ Stigmata of systemic disease (hepatic disease, infection etc)
◦ Conscious level
◦ Pupillary size and responses (pinpoint pupils in narcotic overdose/
pontine haemorrhage; dilated in TCA overdose; single enlarged
unreactive pupil from stretching of third nerve by mass effect; both
dilated and unreactive in midbrain compression/ infarction)
◦ Eye movements/ OCR (drowsy patients may have dysconjugate gaze;
with deeper coma this corrects; absent OCR suggests severe brainstem
damage; tonic eye deviation may suggest focal brain pathology or
seizure activity)
◦ Myoclonus (including asterixis)
Case KR

◦ MRI brain: normal apart from partially empty

sella
◦ EEG (to rule out non-convulsive status):
diffusely slow (encephalopathic)

https://emedicine.medscape.com/article/1140530-overview
Causes
◦ Vascular ◦ Drugs, CO, Alcohol
intoxication
◦ Hypertensive
encephalopathy, hypoxic ◦ Anaesthesia
ischaemic brain injury, ◦ Urinary retention/
right parietal stroke constipation

◦ Infective ◦ Autoimmune
◦ Systemic infection (esp ◦ TTP
UTI, LRTI) ◦ Autoimmune (limbic)
◦ CNS infection encephalitis, CNS lupus
◦ HIV

◦ Trauma/ Toxins
◦ Traumatic brain injury
Causes
◦ Metabolic
◦ Hyper/Hypo Na,
◦ Congenital/ Degenerative
hypercalcaemia,
hyperglycaemia ◦ Epilepsy, Dementia with
(especially if Lewy Bodies
hyperosmolar), uraemia,
hepatic encephalopathy ◦ Endocrine
◦ Hyper/hypothyroidism,
◦ Iatrogenic hypopituitarism
◦ Drugs
◦ Functional
◦ Neoplastic
◦ CNS mets with mass
effect
Tests to consider in encephalopathy
First line: FBC, U&Es, LFTs, bone profile, Glucose, TFTs, B12, CRP, HIV, blood cultures
ABG
Urine dip, CXR
Second line: Toxicology, 9am cortisol, short synacthen test
Plasma and urine osmolalities
CT head
CSF (may be first line depending on history)
Third line: MRI brain
EEG (to rule out subclinical seizures, or functional pseudocoma)
Case KR

◦ Further endocrine testing and opinion did not suggest panhypopituitarism

◦ She was treated with fluids and insulin for HHS, and aciclovir was withdrawn with resolution of the
AKI
◦ (Don’t forget thromboprophylaxis!)
Case KR

◦ Further endocrine testing and opinion did not suggest panhypopituitarism

◦ She was treated with fluids and insulin for HHS, and aciclovir was withdrawn with resolution of the
AKI
◦ (Don’t forget thromboprophylaxis!)
◦ 3 days later she was awake and smiling, eating and drinking, talking and walking!
◦ Her anticonvulsant was stopped and she is going home today
Case KR: causes of encephalopathy?

◦ Prolonged systemic inflammatory response following COVID-19 infection

◦ Drugs (metoclopramide)
◦ Under-nutrition and hydration
◦ HHS (iatrogenic)
◦ AKI (iatrogenic)
Delirium: why does it matter?
◦ Very very common
◦ ‘Confused ? Cause’ forms a large part of the medical take
◦ 1/3 of over-65s in hospital will develop delirium
◦ People in ITU, post-stroke, post-hip fracture, people with terminal illness
Why does it matter?
◦ Risk of self-harm (falls, prevention of proper care)
◦ 1/3 of patients over 65 admitted to hospital will experience
delirium
◦ 50% mortality at 1 year
◦ Risk of institutionalization
◦ Increased length of stay (and hence complications etc)

◦ Delirium is an independent risk factor for these poor outcomes

Why does it matter?
◦ Very frightening
◦ As distressing as pain
◦ For loved ones, can be even more distressing than pain
◦ May not all be forgotten
VENGEANCE, PLAGUE,
DEATH, CONFUSION!
Shakespeare, King Lear
Management
◦ Maximise orientation: make sure they have their glasses, hearing aids etc
◦ Make sure they can see a clock; orientation board with day, date, location
◦ Familiar pictures etc
◦ Encourage family visits, involve families in care
◦ Good lighting
◦ Consistent nursing staff; consider 1:1 nursing
◦ Side-room (but beware of falls)
◦ Minimise bed moves
◦ Pain relief
◦ Good nutrition and hydration
◦ Find a staff-member who speaks their language
Medication
◦ Only if absolutely necessary (if agitation is causing a risk to self or others, and simple measures are not
helping)
◦ Consider 1:1 special instead
◦ Lowest effective dose, ideally oral rather than IM
◦ Benzos (can worsen / cause delirium)
◦ Haloperidol (but dangerous for those with dementia, especially DLB)
Take home points
◦ Think of delirium
◦ Identify the cause
◦ Treat the cause
◦ Supportive management is key
EXPERIENCE IS NOT WHAT HAPPENS TO
A MAN; IT IS WHAT A MAN DOES WITH
WHAT HAPPENS TO HIM
ALDOUS HUXLEY