Differentials

Common

Dementia

History

chronic impairment of memory with 1 or more of the following criteria: aphasia, apraxia, agnosia, and disturbances in executive function; usually not acute and not associated with changes in attention; chronic confusion not associated with changes in alertness and coherence except in the most severe cases; history of long-term cognitive decline from caregivers[89]

Exam

previous cognitive status examination (e.g., Folstein Mini-Mental Examination, Montreal Cognitive Assessment) helpful to establish the chronicity of confusional states; chronic confusion more likely dementia; acute on chronic changes can occur in mixed delirium/dementia states[13][52]

1st investigation
  • the diagnosis of dementia is based predominantly on historical factors:

    diagnosis is clinical

Other investigations

    Pain

    History

    pain; may be history of falls or trauma (e.g., causing hip fracture)

    Exam

    tachycardia, tachypnoea, sweating, reluctance to move and distress on movement

    1st investigation
    • diagnosis is clinical:

      causes of underlying pain should be sought (e.g., hip fracture)

    Other investigations

      Stroke and transient ischaemic attack

      History

      acute changes in mental status likely; associated with neurological symptoms: unilateral weakness or numbness; change in vision (unilateral or bilateral); difficulty with speech, comprehension; loss of co-ordination, difficulty walking; severe headache[90]

      Exam

      confusion frequently noted; focal neurological signs include: unilateral hemiparesis, hemianopia, aphasia, ataxia[90]

      1st investigation
      • neuroimaging (CT and/or MRI):

        ischaemic stroke: hyperdense vessels at the site of blood clot in middle cerebral artery (MCA), posterior cerebral artery (PCA) or anterior cerebral artery (ACA); loss of insular stripe located between Sylvian fissure and basal ganglia is frequently associated with early MCA stroke; subtle mass effect; haemorrhagic stroke: hyperdense to grey matter lesion at the site of haemorrhage; mass effect may also be evident but frequently subtle in early stroke[91]

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      Other investigations

        Myocardial infarction

        History

        history of risk factors for CAD (e.g., smoking, hyperlipidaemia, diabetes, family history of CAD); chest pain (often described as heavy, or tight) radiating to arms, back, neck, or jaw; chest pain may be absent in older adults and people with diabetes; dyspnoea; nausea; diaphoresis

        Exam

        delirium is often the only identifiable sign in older patients; other signs may include hypotension; diaphoretic appearance; pallor; tachycardia; bradycardia; new abnormal pulse rhythm; distended jugular veins; other signs of heart failure (e.g, dyspnoea, crackles at lung bases); new heart murmur

        1st investigation
        • ECG:

          ST segment elevation or depression, or T-wave changes

        • serum troponin:

          elevated

        • chest x-ray:

          evidence of pulmonary congestion/ pleural effusion if secondary heart failure; may show enlarged cardiac shadow

        • coronary angiogram:

          presence of thrombus with occlusion of the artery

        Other investigations

          Acute systemic infection

          History

          cough, sputum production, dyspnoea, chest pain, and urinary incontinence; common causes, especially in older people, are pneumonia and urinary tract infections; systemic infections and sepsis can cause delirium separate from their hypoxic effect[92][93][94][95][96]

          Exam

          pyrexia, rigors, rales, and crackles on auscultation of chest; cloudy urine with offensive odour, hypotension

          1st investigation
          • basic test panel (FBC, serum electrolytes, blood glucose, serum liver function tests, coagulation profile):

            elevated WBC count or leukopenia with sepsis; may be elevated urea and creatinine with sepsis; may be low platelets with sepsis; blood glucose may be elevated or, more rarely, low with sepsis; serum transaminases and serum bilirubin may be elevated with sepsis; may be prolonged or elevated INR, PT, aPTT

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          • ECG:

            normal; may demonstrate tachycardia

          • chest x-ray:

            consolidation from pneumonia

          • blood cultures:

            identification of pathogens

          • arterial blood gas:

            may be hypoxia, hypercapnia, elevated anion gap, metabolic acidosis with sepsis

          • serum lactate:

            may be elevated: >2 mmol/L (>18 mg/dL)

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          • sputum culture:

            identification of pathogens

          • urinalysis and urine culture:

            identification of pathogens; increased white cell count

          Other investigations

            Hypoglycaemia

            History

            confusion, sweating, nausea, headache, drowsiness, and seizures; usually a history of taking medication for diabetes, or alcohol abuse

            Exam

            tremor, sweating, tachycardia

            1st investigation
            • plasma glucose:

              diabetes-related hypoglycaemia: <3.9 mmol/L (70 mg/dL)

              More
            Other investigations

              Hyperglycaemia

              History

              polyuria, polydipsia, weakness, nausea, vomiting, drowsiness, and weight loss, developing rapidly over a day or less; may be precipitated by infection, MI, stroke, or other endocrine disorders

              Exam

              signs of volume depletion, including tachycardia and hypotension, Kussmaul's respiration, acetone breath, stupor, or coma

              1st investigation
              • plasma glucose:

                elevated

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              • serum electrolytes:

                low sodium, chloride, magnesium and calcium; elevated potassium

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              • urinalysis:

                positive for glucose and ketones (DKA)

              Other investigations
              • ABG:

                pH 7.0 to 7.3

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              Hypoxia

              History

              usually secondary to underlying disease such as sepsis, pneumonia, pulmonary embolism, severe asthma attack, COPD, cardiac failure or arrhythmia, or carbon monoxide poisoning; symptoms include inco-ordination, confusion, poor judgement, seizures, myoclonic jerks, euphoria, nausea, visual impairment, coma

              Exam

              increased respiratory rate, tachycardia, cyanosis, poor co-ordination

              1st investigation
              • pulse oximetry:

                <95% oxygen saturation

              • ECG:

                tachycardia, arrhythmia, or ischaemia/infarction

              • chest x-ray:

                consolidation due to pneumonia, signs of infarction from pulmonary embolus, hyperinflation from COPD, cardiomegaly from congestive cardiac failure

              Other investigations
              • D-dimer:

                positive if thromboembolic disorder

              • multidetector computed tomographic pulmonary angiography (CTPA):

                detection of thrombus in pulmonary artery

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              Hypercapnia

              History

              history of abnormal respiratory function (e.g., COPD)

              Exam

              dyspnoea, cyanosis; may have a flapping tremor of the hands, warm peripheries, bounding pulse, and occasionally papilloedema

              1st investigation
              • ABG:

                PaCO2 >6.5 KPa (49 mmHg), when breathing room air at sea level

              Other investigations

                Acute urinary obstruction

                History

                inability to urinate, abdominal pain; may be history of poor urinary stream, hesitancy, dribbling, nocturia, dysuria

                Exam

                bladder distension, may be enlarged prostate

                1st investigation
                • trial of catheter:

                  rapid improvement of symptoms with drainage of urine

                Other investigations
                • pelvic ultrasound:

                  enlarged bladder

                Medication- or illicit drug-related

                History

                overdoses with anticholinergics, tricyclic antidepressants, stimulants, opiates, steroids, analgesics, cardiac glycosides, and anti-Parkinson drugs can be associated with delirium; there may be a history of known illicit drug abuse[52]

                Exam

                may be signs of underlying illnesses requiring predisposing medication; may be signs of illicit drug overdose (e.g., agitation, tachycardia, hyperthermia, mydriasis with amphetamine or cocaine overdose; decreased respiratory rate and miosis with opiate overdose)

                1st investigation
                • ECG:

                  arrhythmias associated with drug toxicity

                Other investigations
                • serum levels of drugs:

                  may be elevated

                • urine levels of drugs:

                  may be elevated

                Alcoholic ketoacidosis

                History

                may be history of recent heavy consumption of alcohol; symptoms of ketoacidosis include nausea and vomiting, abdominal pain, fatigue, poor appetite, lethargy, and confusion

                Exam

                alcoholic ketoacidosis causes reduced consciousness, agitation, rapid ventilation rate, and signs of dehydration

                1st investigation
                • urine ketones:

                  positive

                • blood alcohol level:

                  may be elevated

                • serum electrolytes and urea:

                  high anion gap metabolic acidosis; low potassium, magnesium, and phosphorus

                Other investigations
                • ABG:

                  pH 7.0 to 7.3

                • liver function tests, gamma GT:

                  abnormal if alcoholic liver disease

                Hepatic encephalopathy

                History

                history of hepatitis infection, alcohol use, and/or drug use may be present

                Exam

                hallmark finding in metabolic encephalopathies is asterixis; features of chronic liver disease, encephalopathy, jaundice, hepatomegaly, and ascites may be present

                1st investigation
                • liver tests:

                  elevated or normal liver enzymes; elevated or normal bilirubin; decreased or normal albumin

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                • coagulation tests:

                  elevated or normal prothrombin time

                Other investigations

                  Renal failure

                  History

                  historical findings might include a change in the quantity or quality of urine output, anorexia, and/or NSAID use

                  Exam

                  hallmark finding in metabolic encephalopathies is asterixis; myoclonic jerks may be evident in uraemia; pallor, oedema, pleural effusion, pericarditis, neuropathy, and hypertension may be found

                  1st investigation
                  • renal tests:

                    creatinine >884 micromol/L (10.0 mg/dL); elevated urea

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                  Other investigations

                    Hypernatraemia

                    History

                    recent changes in hypertensive medications, dehydration, inability to obtain water (e.g., as evident with stroke, dementia)[22]

                    Exam

                    mental status changes, weakness, neuromuscular irritability, and or coma/seizures[22]

                    1st investigation
                    • serum electrolytes:

                      Na >145 mmol/L (145 mEq/L)

                    Other investigations

                      Hyponatraemia

                      History

                      recent infection, recent medication change and/or free water intoxication, history of hypotonic intravenous infusions; symptoms of headaches, nausea, confusion, lethargy[22]

                      Exam

                      confusion, seizures, coma[22]

                      1st investigation
                      • serum electrolytes:

                        Na <135 mmol/L (135 mEq/L)

                      Other investigations

                        Hypercalcaemia

                        History

                        history of hyperparathyroidism, malignancy, and/or thiazide diuretic use; symptoms of fatigue, anorexia, nausea, constipation, and polyuria[99]

                        Exam

                        confusion[99]

                        1st investigation
                        • serum calcium (Ca):

                          Ca >2.88 mmol/L (11.5 mg/dL)

                        Other investigations

                          Meningitis/encephalitis

                          History

                          headache, neck stiffness, photophobia, and acute mental status changes; fevers, chills, nausea, and other evidence of illness also common; mental status changes acute or subacute

                          Exam

                          findings associated with meningeal inflammation: acute fulminant illness and triad of fever, headaches, and nuchal rigidity; in meningococcaemia, maculopapular rash and/or petechial rash[100]

                          1st investigation
                          • lumbar puncture and culture of CSF:

                            opening pressure >180 mm H20, elevated WCC count present in CSF, pathogens identified on culture[100]

                          • CT head:

                            consider prior to lumbar puncture to evaluate for intracranial pathology depending on the clinical situation

                          Other investigations

                            Brain tumour

                            History

                            delirium can occur in people with malignant disease either because of structural brain lesions, infection, drugs (especially opioids), or metabolic encephalopathy; symptoms include lethargy, coma, agitation, disorientation, delusions, hallucinations, and seizures[55][56]

                            Exam

                            lateralising neurological signs, papilloedema

                            1st investigation
                            • serum electrolytes:

                              abnormal calcium, sodium, potassium

                              More
                            Other investigations
                            • CT or MRI head:

                              presence of tumour

                            Post-ictal state

                            History

                            loss of consciousness, observed seizure activity, urinary incontinence, tongue trauma may be reported; premonitory symptoms or signs

                            Exam

                            observed tonic-clonic seizure or abnormal movements followed by drowsiness

                            1st investigation
                            • EEG:

                              synchronous epileptiform activity during a seizure; slowing of background elements, dampened reactivity and loss of normal architecture immediately after a seizure

                            Other investigations
                            • head MRI or CT:

                              usually normal, may show focal abnormalities

                            Dehydration (volume depletion)

                            History

                            thirst; fatigue; muscle cramps; abdominal pain; chest pain; confusion; loss of weight; underlying cause of volume loss including diarrhoea, vomiting, burns, poor oral intake, severe sweating, severe pancreatitis, GI or intra-abdominal haemorrhage; polyuria from diabetes; crush injury, intestinal obstruction

                            Exam

                            dry mucous membranes; orthostatic hypotension; postural tachycardia; shock; decreased skin turgor; decreased urine output

                            1st investigation
                            • FBC:

                              increased haematocrit; high haemoglobin

                            • serum electrolytes:

                              hyper- or hypokalaemia; hyponatraemia

                            • urinalysis:

                              specific gravity >1.010

                            • serum creatinine, urea:

                              urea/creatinine ratio >20

                            Other investigations

                              Constipation

                              History

                              altered bowel habits; abdominal pain; pain on defecation

                              Exam

                              tender abdomen; mass on palpation

                              1st investigation
                              • abdominal x-ray:

                                dilated loops of bowel; faecal loading in right colon

                              Other investigations

                                Uncommon

                                Traumatic head injury

                                History

                                loss of consciousness, anterograde and retrograde amnesia, vomiting, headache

                                Exam

                                deformity of skull or open fracture, reduced Glasgow coma scale (based on eye, verbal, and motor response), abnormal or unequal pupil reflexes, bruising around eyes or ears, bleeding or leakage of CSF from nose or ears, associated injuries to other parts of the body

                                1st investigation
                                • head CT:

                                  fracture of skull, intracranial bleeds and microhaemorrhage

                                  More
                                Other investigations

                                  Adrenal crisis

                                  History

                                  caused by stress, trauma, or infection in a patient with Addison's disease, or damage to the adrenal gland or pituitary; symptoms include headache, weakness, nausea, vomiting, fatigue, confusion, sweating, joint pain, abdominal pain, and weight loss

                                  Exam

                                  tachycardia, increased respiratory rate, hypotension, rash or darkening of the skin

                                  1st investigation
                                  • serum electrolytes:

                                    high potassium, low sodium

                                  • plasma glucose:

                                    low

                                    More
                                  Other investigations
                                  • ACTH stimulation test:

                                    low cortisol levels

                                  Thyrotoxicosis

                                  History

                                  change in appetite, weight loss, anxiety, palpitations, sweating and heat intolerance, oligomenorrhoea, mood change, and fatigue

                                  Exam

                                  goitre, lid lag, exophthalmos, tachycardia, proximal muscle weakness, and tremor; thyroid storm also causes high fever and coma

                                  1st investigation
                                  • thyroid function tests:

                                    elevated free T4 and/or free T3; suppressed TSH

                                  Other investigations

                                    Myxoedema coma

                                    History

                                    reduced consciousness, usually in older patient with infection or over-sedation; may also be weight gain, depression, lethargy, feeling cold, forgetfulness, and constipation

                                    Exam

                                    coma, hypothermia, bradycardia, signs of cardiac and respiratory failure, dry skin, facial and eyelid oedema, and thick tongue

                                    1st investigation
                                    • TSH:

                                      elevated in primary hypothyroidism; may be low, normal, or slightly elevated in central hypothyroidism

                                    • free T4:

                                      low

                                    Other investigations

                                      Brain abscess

                                      History

                                      fever, headache, motor weakness, neck stiffness, vomiting, visual disturbance, seizures, impaired consciousness[102]

                                      Exam

                                      pyrexia, hemiparesis, focal neurological abnormalities, septic shock, meningism, papilloedema[102]

                                      1st investigation
                                      • CT or MRI head:

                                        identification of abscess

                                      Other investigations
                                      • CSF culture:

                                        isolation of pathogens

                                      • blood culture:

                                        isolation of pathogens

                                      Neurosyphilis

                                      History

                                      personality change, gait impairment, incontinence, headache, lightning pains, blurred vision, photophobia, reduced colour perception

                                      Exam

                                      hyporeflexia, ataxia, anisocoria, Argyll Robertson pupils, cranial neuropathy, dementia, paranoia, Charcot's joint

                                      1st investigation
                                      • cerebrospinal fluid examination and Venereal Disease Research Laboratory (VDRL):

                                        lymphocytic pleocytosis, elevated protein, reactive VDRL

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                                      Other investigations
                                      • fluorescent treponemal antibody test-absorption (FTA-abs):

                                        positive

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                                      • CT or MRI head:

                                        generalised cerebral atrophy with ventricular dilatation

                                      Wernicke's encephalopathy

                                      History

                                      may be history of long-term, heavy consumption of alcohol or recent withdrawal; Wernicke's encephalopathy and Korsakoff's syndrome can be caused by thiamine deficiency and can contribute to delirium; symptoms include loss of co-ordination, confusion, memory impairment, change in vision, anxiety, delusions, insomnia, and delirium

                                      Exam

                                      confusion, nystagmus, conjugate gaze palsy, ataxia, short-term memory loss, hypothermia, hypotension, peripheral neuropathy, confabulation

                                      1st investigation
                                      • therapeutic trial of parenteral thiamine:

                                        clinical response to treatment

                                      Other investigations
                                      • blood alcohol level:

                                        may be elevated

                                      • liver function tests, gamma GT:

                                        abnormal if alcoholic liver disease

                                      • blood thiamine and its metabolites:

                                        usually low

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