4.3.3 Physical assessment and investigations

Assessment of physical factors and investigations

Why assess physical health

• Physical assessment finds medical causes of psychiatric symptoms, coexisting illness, emergencies and treatment effects, and it sets baselines for later monitoring.

• Diagnostic overshadowing happens when a psychiatric diagnosis stops clinicians from investigating new physical symptoms.

Red flags for an organic cause

Bedside observations and conscious level

• Record vital signs, oxygen saturation, glucose, hydration and conscious level, and check glucose promptly in any altered mental state.

Glasgow Coma Scale

The Glasgow Coma Scale (GCS) total is the sum of the best eye, verbal and motor responses. It runs from 3 to 15 because no component has a zero grade.

• Abnormal flexion (decorticate posturing, with the arms drawn towards the chest) scores M3.

• Abnormal extension (decerebrate posturing, with the arms extended and rotated inwards) scores M2.

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• Report the three components as well as the total, and note anything that stops a component being tested.

• A score band alone does not decide airway protection: assess airway, breathing and circulation directly and escalate reduced consciousness.

Caloric testing

• Caloric testing separates psychogenic unresponsiveness from organic coma: if cold water in one ear produces nystagmus with its fast phase away from that ear, the patient is physiologically awake.

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General examination

• Look for commonly missed problems: infection, injury, urinary retention, constipation, dehydration, pressure damage and drug effects.

Body mass index and body measures

• Body mass index (BMI) is weight in kilograms divided by the square of height in metres, in kg/m squared.

• Square the exact height; rounding it first gives the wrong answer.

• Weight can be recovered by rearranging the formula: weight equals BMI times height in metres squared.

The World Health Organization (WHO) adult bands have cut-offs at 18.5, 25, 30, 35 and 40.

• Interpret BMI alongside ethnicity and body composition; children need age-adjusted measures.

• Waist-to-height ratio measures central adiposity: 0.4 to 0.49 carries no increased risk, 0.5 to 0.59 increased risk and 0.6 or more high risk.

Eating disorders

• Lanugo is fine, soft, downy body hair that grows in starvation, as in restricting anorexia nervosa without purging.

• Russell's sign is callusing or abrasion over the knuckles of the dominant hand, where the incisors graze it during repeated self-induced vomiting, as in bulimia nervosa.

• Anorexia nervosa also causes bradycardia and hypothermia.

• A BMI below 16 makes an electrocardiogram (ECG) a routine part of the initial physical risk assessment in anorexia nervosa.

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Physical effects of psychotropic drugs

Medical causes of psychiatric presentations

• Goitre, proximal weakness, hair thinning and menstrual disturbance occur in both hyperthyroidism and hypothyroidism, so they do not separate the two, whereas the deep tendon reflexes change in opposite directions.

• B12 deficiency can occur without anaemia or macrocytosis, so a normal blood count does not exclude it.

Wilson's disease

• Wilson's disease (older name, hepatolenticular degeneration) is copper damage to the liver and the lenticular nucleus, which is the putamen with the globus pallidus.

• It presents in adolescence or early adulthood with psychiatric change, cognitive decline and involuntary movements, linking liver abnormality with a basal ganglia movement disorder in a young person.

• It is autosomal recessive, so each sibling has a 1 in 4 risk; juvenile Huntington's disease is autosomal dominant, with a 50% risk.

• The Kayser-Fleischer ring is a golden-brown ring of copper in Descemet's membrane at the corneal margin, seen on slit-lamp examination, and is the diagnostic eye sign.

• Only Wilson's disease deposits copper in the cornea, which separates it from haemochromatosis.

• Caeruloplasmin is low, so total serum copper is low, while urinary copper is raised and free copper accumulates in liver and brain.

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Neurological examination

• Examine mental state, cranial nerves, visual fields, eye movements, motor and sensory systems, reflexes, coordination and gait, adding fundoscopy where indicated.

• Confrontation testing examines the visual fields at the bedside and detects defects from lesions along the visual pathway, such as the bitemporal hemianopia of a chiasmal lesion.

Pupils

Light-near dissociation is a pupil that constricts to a near target but not to light.

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• Opioid intoxication causes pinpoint pupils, which naloxone reverses.

Cerebellar and pyramidal signs

• Limb ataxia with dysmetria and dysdiadochokinesia localises to the cerebellar hemisphere on the same side, with power, reflexes and proprioception intact.

• Dysmetria and intention tremor on the finger-nose test come from a lesion of the dentate nucleus, in the cerebellar circuit that coordinates limb movement.

• Pronator drift is an outstretched arm that pronates and sinks on one side; it marks mild upper motor neurone weakness from the contralateral cerebral hemisphere.

• In a heavy drinker with fluctuating confusion and new one-sided weakness, pronator drift supports a chronic subdural haematoma.

Gait and balance

• Romberg's sign is positive when the patient stands steady with eyes open but becomes unsteady with eyes closed, with normal limb coordination.

• A positive Romberg's sign indicates sensory (proprioceptive) ataxia, as in tabes dorsalis, not cerebellar ataxia.

• A steppage gait, with high knee lift and forefoot slap but balance kept with eyes closed, signals foot drop from weak ankle dorsiflexion.

• Steppage gait is a motor gait, not a sensory, cerebellar, spastic or waddling one.

Asterixis

• Asterixis is a flapping tremor and the bedside sign of hepatic encephalopathy, as after a variceal bleed in cirrhosis, and of other metabolic organ failure.

• Elicit it with the arms outstretched and wrists extended: the sustained posture reveals negative myoclonus as lapses in that posture.

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Reflexes and other named signs

• Frontal release (primitive) reflexes re-emerge when frontal inhibition is lost, though their specificity for frontal disease varies.

• Superficial cutaneous reflexes are distinct: they are normally present in adults and are lost with corticospinal disease.

• The knee-extension test is Kernig's sign, not Brudzinski's, Lasègue's or Romberg's sign.

• Absent meningeal signs do not exclude meningitis.

Localising syndromes

Alcohol misuse

Signs

• Alcohol-related signs arise from liver disease, altered sex hormone handling and direct tissue effects: liver and nutritional signs, parotid swelling, Dupuytren's contracture and gynaecomastia.

• No single sign proves that alcohol caused the problem.

• Gynaecomastia reflects a specific alcohol-related endocrine and hepatic mechanism.

• Abdominal striae are the least reliable sign, because pregnancy, puberty, weight change, Cushing's syndrome and steroids all stretch the dermis.

• Exophthalmos is an eye sign of Graves' disease and has no link with alcohol misuse.

Wernicke encephalopathy and delirium tremens

• Wernicke encephalopathy comes from thiamine deficiency (alcohol, hyperemesis, bariatric surgery) and gives confusion, wide-based gait ataxia and eye signs.

• Nystagmus is the commonest eye sign; ophthalmoplegia, often a lateral rectus palsy, also occurs.

• Never delay urgent thiamine to wait for a test.

• Delirium tremens usually starts 2 to 3 days after the last drink, with coarse tremor, sweating, tachycardia, fever and raised blood pressure.

Screening and blood markers

• The AUDIT (Alcohol Use Disorders Identification Test) is a ten-item WHO questionnaire on consumption, dependence symptoms and harm, and the recommended screen in UK primary care.

• An AUDIT score of 8 or more suggests hazardous or harmful drinking.

• Platelets tend to fall, not rise as MCV, GGT and transaminases do, through marrow toxicity to megakaryocytes, folate deficiency and splenic sequestration in cirrhosis.

• These markers support an assessment of alcohol-related harm but cannot diagnose dependence or measure intake accurately.

Blood and targeted investigations

• Toxicology shows exposure, not causation, and assays have timing limits.

• Urine dipstick testing should not be used routinely to diagnose infection in older adults.

• Valproate carries strict reproductive restrictions, and its psychiatric use in pregnancy is contraindicated.

• Interpret every result against pre-test probability, clinical features, medicines and trends, because reference intervals do not perfectly divide health from disease.

Electrocardiography

• An ECG assesses rhythm, conduction and the corrected QT interval (QTc) when a medicine, cardiac history, symptoms, overdose or electrolyte risk calls for it.

• In eating disorders, rapid weight loss, bradycardia, purging and medicines also prompt an ECG.

• Bazett's formula overcorrects the QT at fast heart rates and undercorrects at slow rates.

Electroencephalography

• Electroencephalography (EEG) helps with suspected seizures, including non-convulsive status, and selected encephalopathies.

• A normal routine EEG does not exclude epilepsy.

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• Sawtooth waves occur only in rapid eye movement (REM) sleep and are absent from every non-REM stage.

• Typical absence seizures give generalised spike-and-wave at about 3 Hz on a normal background.

• Lennox-Gastaut syndrome gives slow spike-and-wave below 2.5 Hz on an abnormal background.

Lumbar puncture

• Cerebrospinal fluid examination helps in suspected central nervous system infection, inflammation and autoimmune encephalitis.

• Before lumbar puncture, check bleeding risk, local infection, instability and signs of brain shift or a mass lesion.

• Imaging before lumbar puncture is needed only in selected cases.

• Never delay antimicrobial treatment to complete investigations.

Neuroimaging

• Request imaging to answer a stated question: focal disease, trauma, unexplained deterioration, rapid cognitive change or atypical presentation.

• Scanning without an indication uncovers incidental findings and may not improve care.

Working knowledge of medicine

Recognising the deteriorating patient

• ABCDE (airway, breathing, circulation, disability, exposure) is the order in which immediate threats are assessed and treated, while help is called.

• Check glucose promptly in any altered mental state and treat hypoglycaemia at once. Do not assume agitation or drowsiness is psychiatric or substance related.

• Sepsis is suspected when infection comes with acute deterioration: altered consciousness, abnormal temperature, rapid breathing, hypotension or hypoxia. Fever may be absent.

• Diagnostic overshadowing is blaming new physical symptoms on an established psychiatric diagnosis. In people who communicate differently, behavioural change may be the first sign of pain or illness.

• Use controlled oxygen targets in people at risk of hypercapnic respiratory failure, but do not withhold oxygen from severe hypoxaemia.

Motor signs and localisation

• Weakness is the only sign the two share.

• Wasting and fasciculation are signs of denervation, so they belong to the LMN and are absent in a pure UMN lesion. Marked wasting cannot occur without denervation.

• Bulbar palsy is an LMN lesion of cranial nerves IX to XII, with an absent gag reflex and a wasted, fasciculating tongue. Pseudobulbar palsy is the UMN pattern.

• Motor neurone disease mixes LMN signs (wasting, fasciculation) with UMN signs (spasticity, brisk reflexes, extensor plantars) and spares sensation.

• Absent ankle jerks with extensor plantars mean the reflex arc and the corticospinal tract are damaged together: subacute combined degeneration, Friedreich's ataxia, taboparesis or motor neurone disease.

• Waddling (myopathic) gait is a rolling gait with pelvic sag on each side, a wide base and exaggerated lumbar lordosis, from bilateral proximal pelvic girdle weakness.

• Asterixis marks a metabolic encephalopathy, such as hepatic encephalopathy or carbon dioxide retention after uncontrolled high-flow oxygen in severe chronic obstructive pulmonary disease.

• Multiple spider naevi in the superior vena cava territory are a sign of chronic liver disease, most often alcoholic, because the liver clears less oestrogen. Isolated ones occur in healthy people.

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Fatigable weakness and fatigue

• Myasthenia gravis is fatigable weakness from the neuromuscular junction: it worsens with sustained use and recovers with rest, mainly in ocular and bulbar muscles. It can be mistaken for a stress-related psychiatric presentation.

• Lambert-Eaton myasthenic syndrome, suggested by heavy smoking, differs from myasthenia gravis by reduced reflexes, proximal leg weakness and autonomic features.

• In myasthenia gravis a selective serotonin reuptake inhibitor (SSRI) is generally well tolerated, whereas lithium, benzodiazepines and antipsychotics can worsen weakness or its respiratory consequences.

• In myalgic encephalomyelitis/chronic fatigue syndrome, fatigue that rest does not substantially relieve is a defining criterion.

Pupils and visual pathways

• The ophthalmic artery is the first branch of the internal carotid and supplies the ipsilateral retina. Transient monocular visual loss needs urgent assessment.

• Cortical blindness leaves pupillary light reflexes intact, because reflex fibres leave the optic tract before the lateral geniculate nucleus, and the patient knows they cannot see.

• Anton's syndrome is the same lesion with denial of the blindness and confabulation.

• Adie's (Holmes-Adie) tonic pupil is a unilateral dilated pupil in a well young adult, with poor light response, slow sustained constriction on near effort and slow redilation.

• Pontine haemorrhage mimics opioid intoxication with pinpoint pupils and coma. Loss of brainstem reflexes, bilateral pyramidal signs, hypertension and central fever point to the pons.

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Stroke, subdural haematoma and headache

• A sudden focal deficit (weakness, sensory loss, language disturbance, visual loss or ataxia) needs urgent stroke assessment.

• In an older person, a sudden focal deficit with new low mood and forgetfulness points to stroke, which explains all three through post-stroke depression and vascular cognitive impairment.

• A consistent inter-arm blood pressure difference points to atherosclerotic stenosis of the subclavian artery on the side of the lower reading.

• Chronic subdural haematoma follows head injury in an anticoagulated older adult after weeks, with cognitive slowing, sleepiness, headache and a focal sign. Computed tomography (CT) shows a crescent-shaped collection over the convexity.

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Headache

• Headache provoked by manoeuvres that raise intracranial pressure (bending, coughing, sneezing, straining) is a red flag for intracranial pathology rather than tension-type headache.

• New thunderclap headache, papilloedema and focal signs also need urgent investigation.

Migraine aura

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• Migraine aura is fully reversible with insight intact, even when no headache follows.

• These patterns overlap, so they cannot safely exclude stroke.

• Stress and irregular or missed meals are recognised precipitants of migraine, the latter probably through falling blood glucose.

Functional neurological disorder

• Conversion disorder (functional or dissociative neurological symptom disorder) can present as abrupt weakness after a psychological stressor, with normal objective signs and internal inconsistency. It is not intentionally produced and has no external incentive.

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• Positive functional signs support the diagnosis in context. They do not prove deliberate symptoms or rule out coexisting disease.

Epilepsy

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• An aura is the conscious onset of a focal seizure, most typical of temporal lobe seizures, and is absent in seizures generalised from the start.

• Automatisms are brief, stereotyped actions performed with impaired awareness, usually in focal temporal lobe seizures, with amnesia for the episode.

• NICE (National Institute for Health and Care Excellence) offers lamotrigine or levetiracetam as first-line monotherapy for newly diagnosed focal seizures, not sodium valproate.

• The number of generalised tonic-clonic seizures is the strongest predictor of sudden unexpected death in epilepsy (SUDEP), more than nocturnal timing.

• A convulsive seizure lasting five minutes, or repeated convulsions without recovery, needs emergency treatment for status epilepticus.

Functional (dissociative) seizures

• Prolactin raised 10 to 20 minutes after an event is about 96% specific for an epileptic seizure, but it shifts probability only modestly and cannot settle the diagnosis.

• Video-EEG telemetry that captures a habitual attack settles whether attacks are epileptic or functional. Magnetic resonance imaging (MRI) and post-event blood markers cannot.

• Dissociative seizures are genuine and involuntary, with no conscious intent, unlike the deliberate symptom production of factitious disorder and malingering.

• No single sign is diagnostic, and dissociative seizures can coexist with epilepsy.

• Therapy built on a cognitive behavioural model is the best-supported psychological treatment, ahead of psychodynamic psychotherapy.

Dementia and its mimics

• The one-year rule separates dementia with Lewy bodies (dementia before or within a year of parkinsonism) from Parkinson's disease dementia.

• Lewy bodies are intraneuronal cytoplasmic inclusions of aggregated alpha-synuclein with ubiquitin, unlike plaques and tangles, spongiform change or Pick bodies.

• Haloperidol is contraindicated in Parkinson's disease and dementia with Lewy bodies.

• Charles Bonnet syndrome is complex, well-formed visual hallucinations in a person with severe visual loss, intact cognition and insight, arising from visual deafferentation.

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Delirium and catatonia

• Delirium develops acutely and fluctuates, affecting attention and cognition. The hypoactive form can resemble depression or dementia; the 4AT is one assessment tool.

• Drug precipitants of delirium include anticholinergics, opioids, benzodiazepines and sedating antipsychotics.

• Urinary retention can cause delirium, particularly with anticholinergics or opioids. Asymptomatic bacteriuria is common in older adults, so urine dipsticks should not be used routinely to diagnose infection.

• Neurological causes of catatonia include post-encephalitic states, parkinsonism, seizures, general paresis and lesions of the basal ganglia, thalamus, or parietal or frontal lobes.

Autoimmune encephalitis

• Neuronal surface antibodies are pathogenic and the encephalitis responds to immunotherapy.

• Intracellular antigen encephalitis is paraneoplastic and treatment-resistant, because T cells destroy neurones irreversibly.

• Immunoglobulin G (IgG) against the GluN1 (NR1) subunit of the N-methyl-D-aspartate (NMDA) receptor carries diagnostic weight. IgM and IgA antibodies are non-specific and also occur in schizophrenia and healthy people.

• Cerebrospinal fluid (CSF) antibody testing establishes the diagnosis, being more sensitive and specific than serum; imaging, EEG and biopsy do not.

Anti-NMDA receptor encephalitis

Anti-NMDA receptor encephalitis typically affects a young woman, often with an ovarian teratoma, who tolerates antipsychotics poorly. The course is staged:

1. A psychiatric prodrome comes first and is followed by psychosis.

2. Dyskinesias, catatonia, seizures, reduced consciousness and autonomic instability then develop.

• Anti-NMDA receptor antibodies are the commonest cause of relapse weeks after herpes simplex encephalitis with negative polymerase chain reaction (PCR). Young children show choreoathetosis and orofacial dyskinesia.

Other antibodies

• Stiff person syndrome shows axial rigidity, lumbar hyperlordosis and startle-provoked spasms, with relief in sleep and response to diazepam. Fear of walking may be mistaken for agoraphobia.

Infections

• Suspected bacterial meningitis needs urgent antibiotics, and suspected herpes simplex encephalitis needs empirical aciclovir.

Human immunodeficiency virus (HIV)

• HIV is a retrovirus: an RNA virus that copies its genome into DNA with its own reverse transcriptase and integrates it into the host genome as a provirus.

• HIV can present with low mood; fever with generalised lymphadenopathy in a depressed patient with high-risk sexual or injecting exposure points to it.

• Cerebral toxoplasmosis, reactivation of Toxoplasma gondii at low CD4 counts, is the usual cause of multiple ring-enhancing brain lesions with oedema in advanced HIV.

• Kaposi's sarcoma, a vascular tumour driven by human herpesvirus 8, causes painless, non-blanching purple-red macules and plaques on skin and oral mucosa in the acquired immune deficiency syndrome (AIDS).

Syphilis

• General paresis (late parenchymal neurosyphilis) presents in midlife, a decade or more after Treponema pallidum infection.

• It shows grandiosity, irritability or paranoia with progressive cognitive decline, dysarthria, UMN signs and Argyll Robertson pupils.

• Serum treponemal serology is the first test when neurosyphilis is suspected; CSF examination follows only after a positive result.

Other infections with psychiatric features

The electrocardiogram and cardiac effects

• The normal PR interval is 120 to 200 ms in both sexes.

• The upper limit of the corrected QT interval (QTc) is lower in men than in women, so 448 ms is normal in a woman and 454 ms is prolonged in a man.

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• A small U wave on its own can be normal.

• Low potassium, magnesium and calcium lengthen ventricular repolarisation and the QTc; high calcium shortens the QT. QT-prolonging drugs and electrolyte disturbance combine to raise the risk of torsades de pointes.

• Hyperkalaemia occurs in rhabdomyolysis after a long lie.

• An angiotensin blocker plus a non-steroidal anti-inflammatory drug (NSAID) added to lithium cuts renal lithium clearance and perfusion, so lithium accumulates, the kidneys fail and hyperkalaemia follows.

Psychotropics and the heart

• Citalopram blocks human ether-a-go-go-related gene (hERG) potassium channels and prolongs the QT in a dose-related way, with torsades de pointes at excess dose. The maximum is 20 mg daily over 65.

• Tricyclic antidepressants are contraindicated in heart block of any degree, including first-degree, because sodium-channel blockade slows AV and His-Purkinje conduction.

• In tricyclic overdose, a QRS over 100 ms predicts seizures and arrhythmia and calls for intravenous sodium bicarbonate.

• Clozapine myocarditis or pericarditis usually appears within the first two months, with fever, chest pain or breathlessness and raised troponin and C-reactive protein (CRP). Stop clozapine.

• The ECG in clozapine myocarditis is often non-specific, such as sinus tachycardia with minor ST changes.

• Lithium at therapeutic levels most often causes sinus node dysfunction, seen as sinus bradycardia; QTc prolongation is described mainly in toxicity.

Water and sodium

Polyuria and polydipsia

• Diabetes mellitus is the commonest cause of polyuria in adults, through osmotic diuresis.

• Psychogenic (primary) polydipsia is overrepresented in chronic psychotic illness, most of all chronic schizophrenia, and can progress to water intoxication with hyponatraemia, lethargy and vomiting.

• Patients with psychogenic polydipsia rarely report thirst. Management is supervised fluid restriction with weight and sodium monitoring, not desmopressin.

• Polydipsia in psychosis can coexist with impaired water excretion.

• Long-term lithium causes nephrogenic diabetes insipidus. In the water deprivation test, urine stays dilute after fluid is withheld and after desmopressin; hypernatraemia follows if access to water is lost.

Hyponatraemia and SIADH

• SIADH soon after starting an SSRI is the typical drug-induced form; risk is highest in older people, in the first weeks and alongside a thiazide diuretic.

• Female sex is a risk factor for SIADH, particularly the drug-associated form.

• Central nervous system insults cause SIADH: stroke, meningitis, head injury and subarachnoid haemorrhage.

• Hyponatraemia starts with lethargy, headache, nausea, cramps and falls, then progresses to confusion, seizures and coma.

• Seizures occur because a rapid fall in plasma sodium causes cerebral oedema.

• Rapid hypotonic fluid replacement can cause hyponatraemia within hours.

• Severe neurological symptoms need emergency treatment, with controlled correction to avoid osmotic demyelination.

Diabetes and antipsychotics

• Monitor weight and glucose or glycated haemoglobin (HbA1c) during antipsychotic treatment.

• Osmotic symptoms (thirst, polyuria, tiredness) after weight gain on an antipsychotic point to hyperglycaemia, investigated with a fasting plasma glucose.

• Diabetic ketoacidosis can be the first presentation of antipsychotic-induced diabetes, with highest risk on clozapine and olanzapine. Its metabolic acidosis drives deep, rapid compensatory breathing.

Endocrine disorders that mimic psychiatric illness

• In Addison's disease, pigmentation comes from high adrenocorticotropic hormone (ACTH), and the electrolyte change from loss of aldosterone. Adrenal crisis needs immediate hydrocortisone and fluids.

• Phaeochromocytoma is confirmed by raised urinary metanephrines, the O-methylated products of catecholamine breakdown by catechol-O-methyltransferase (COMT).

• Intravenous sodium lactate reliably provokes panic attacks in people with panic disorder but seldom in controls, which is taken as evidence of biological vulnerability.

• Sick euthyroid syndrome is abnormal thyroid function in severe illness without thyroid disease. Triiodothyronine (T3) falls first, from reduced peripheral deiodination of T4; T4 falls later in prolonged illness.

• Pregnancy is the commonest cause of secondary amenorrhoea, so the pregnancy test comes before prolactin, thyroid tests and imaging.

• Antipsychotic-related hyperprolactinaemia is not itself evidence of a tumour.

Calcium

• Long-term lithium raises the calcium level the parathyroid glands tolerate, causing hyperparathyroidism and hypercalcaemia with renal stones, constipation, fatigue and low mood.

• Squamous cell lung cancer causes hypercalcaemia by secreting parathyroid hormone-related peptide; breast cancer and myeloma act through the same peptide or bone destruction.

• Hypocalcaemia after total thyroidectomy, from parathyroid injury, causes perioral and digital paraesthesia and carpal spasm on cuff inflation (Trousseau's sign).

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Medical complications of eating disorders

• Self-induced vomiting causes a hypokalaemic, hypochloraemic metabolic alkalosis. Gastric acid is lost first, then volume depletion drives renal potassium loss, with cramps, weakness and palpitations.

• Anorexia nervosa itself prolongs the QTc through starvation and electrolyte loss.

• Starvation lowers free T3 and raises reverse T3, with TSH normal or low-normal. This reverses with weight restoration, so thyroxine is not given.

• Refeeding syndrome is a sharp fall in serum phosphate over the first days of renewed nutrition, as insulin drives phosphate into cells. It causes muscle weakness, confusion, heart failure and sudden death.

• Refeeding needs supervised nutrition, thiamine and monitoring and replacement of phosphate, potassium and magnesium.

• Bulimia nervosa, rather than restrictive eating, is linked with polycystic ovary syndrome, with insulin resistance and hyperandrogenism as the proposed bridge.

Psychotropic emergencies

• Creatine kinase rises, often into the thousands, in neuroleptic malignant syndrome because rigid muscle breaks down.

• Lithium toxicity follows thiazide diuretics reducing renal lithium clearance. Vomiting and diarrhoea come first, then coarse tremor, dysarthria, ataxia and drowsiness; withhold lithium and check a serum level at once.

• Valproate can cause hyperammonaemic encephalopathy by interfering with the urea cycle, so measure plasma ammonia even when liver tests are normal and the level is therapeutic.

• Clozapine: fever or sore throat needs an urgent blood count for agranulocytosis. Gut hypomotility can cause fatal obstruction or perforation, so ask about bowels and use preventive laxatives where indicated.

• Pulmonary embolism follows immobility such as catatonia, and antipsychotic treatment, with abrupt breathlessness, pleuritic chest pain, tachycardia and hypoxia.

• Chlorpromazine is not porphyrinogenic and is safe in acute intermittent porphyria. Progestogens, barbiturates, NSAIDs and benzodiazepines can precipitate attacks; lithium carbonate is not a recognised precipitant.

Intoxication and withdrawal

The anticholinergic state is told from the sympathomimetic, serotonergic and withdrawal states by dry skin: the others are sweaty.

• Cocaine also causes formication, paranoia, numb gums and a crusted nose from its local anaesthetic action, and chest pain from coronary vasospasm. The high is short, with a crash after about an hour.

• Amphetamine intoxication follows oral use over sleepless days, with a sustained paranoid psychosis, formication, bruxism, punding and raised temperature.

• Amphetamine withdrawal after a binge brings dysphoria, exhaustion, long sleep, increased appetite and vivid unpleasant dreams, without autonomic signs.

• Benzodiazepine withdrawal causes anxiety, insomnia, agitation, nausea, tremor and tachycardia, with perceptual disturbance: hyperacusis, a sense of the floor moving, or limbs felt to be moved (kinaesthetic hallucinations).

• Caffeine withdrawal gives headache, drowsiness, low mood, poor concentration and flu-like aching, starting 12 to 24 hours after the last dose and settling over 2 to 9 days.

• Alcohol withdrawal seizures often occur within 12 to 48 hours; delirium tremens commonly develops later, though timing varies.

• Heroin-associated nephropathy is focal segmental glomerulosclerosis presenting as nephrotic syndrome with oedema and hypertension, commoner in Black heroin users.

Urine detection windows

• A positive result shows exposure, not current intoxication, and a negative result does not exclude all use.

Vitamin deficiencies

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• Nitrous oxide oxidises the cobalt in cobalamin and inactivates it, so heavy use causes functional B12 deficiency with a normal serum level and subacute combined degeneration.

• B12 neurological symptoms can precede anaemia, so a normal blood count does not exclude deficiency.

Wernicke-Korsakoff syndrome

• Wernicke's encephalopathy is the acute triad of confusion, gait ataxia and ophthalmoplegia with nystagmus, from thiamine (vitamin B1) deficiency, classically in alcohol dependence. The full triad is often absent.

• Hypothalamic involvement adds hypothermia and hypotension; the lesions are symmetrical, midline and periventricular.

• The mammillary bodies are the classic and most consistent site of damage.

• Risks include alcohol dependence, malnutrition, hyperemesis and bariatric surgery. Give prompt parenteral thiamine, but never delay emergency glucose for hypoglycaemia.

• Ocular palsies recover first, within hours to days of thiamine; ataxia, nystagmus, neuropathy and memory recover slowly or incompletely. Persistent amnesia suggests Korsakoff syndrome.

Biochemistry

• Thiamine pyrophosphate is a coenzyme for carbohydrate catabolism, and the body cannot make thiamine.

• Deficiency causes failure of thiamine-dependent enzymes: pyruvate dehydrogenase (glucose oxidation), alpha-ketoglutarate dehydrogenase and transketolase (pentose phosphate pathway).

Sleep disorders

Narcolepsy

• Narcolepsy brings sleep attacks despite full sleep, with short refreshing naps, from loss of hypocretin (orexin) neurones. Its classic symptoms also include cataplexy, sleep paralysis and hypnagogic hallucinations.

• Cataplexy is brief loss of muscle tone with preserved awareness, triggered by laughter.

• Sleep paralysis is clear awareness with inability to move or speak, as rapid eye movement (REM) atonia lingers into waking. It is distinct from catalepsy, a catatonic sign.

• Hypnagogic hallucinations occur while drifting off; hypnopompic ones arise as sleep gives way to waking and are common in healthy people.

• The multiple sleep latency test, a daytime nap study after overnight polysomnography, measures sleep latency and sleep-onset REM periods and is the main investigation.

• CSF hypocretin, human leucocyte antigen (HLA) typing and pre-test sleep monitoring also help. Deliberate sleep deprivation has no role, because it shortens sleep latency and confounds the findings.

Parasomnias

• Nightmares arise from REM sleep and are recalled, which separates them from sleep terrors.

• REM sleep behaviour disorder with anosmia hints at an underlying synucleinopathy such as Parkinson's disease or dementia with Lewy bodies.

Movements in sleep

Circadian rhythm disorders

Other

• Obstructive sleep apnoea shows loud snoring broken by silences that end in a snort, from a collapsed upper airway, with fragmented sleep, morning headache and afternoon dozing. Antipsychotic weight gain makes it likelier.

• In post-traumatic stress disorder, raised REM density (more eye movements per minute of REM) is the most consistent polysomnographic finding, with more stage N1 and less slow wave sleep.