Table 4.

Investigation of ‘psychiatric’ presentationsa,b

Routine screening for first psychiatric presentationsFull blood count, urea and electrolytes, calcium, phosphate, liver function tests (including GGT), thyroid function tests, ESR, glucose, urine dipstick, drug screen, chest X-ray if respiratory symptoms; BP, pulse, temperatureExclude obvious causes of delirium, increase chances of detection of relevant general medical condition
B 12 and folate levelsReversible causes of dementia; B 12 deficiency can present with psychosis
Localising signsImaging (CT or MRI)Exclude space-occupying lesion or parenchymal brain damage
Cognitive impairment prominent or psychiatric presentation has atypical features (eg age of onset of psychosis, very changeable and/or fluctuating presentation etc); overt neurological symptoms such as movement disorder or seizures4-h temperature readingsAssist detection of infection, especially HSV or other viral encephalitis c
Imaging, likely MRIExclude space-occupying lesion, identify generalised or localised atrophy, vascular damage, oedema and/or inflammation etc
HIV and syphilis serologyExclude these infectious agents (part of routine screen in some centres)
Consider EEGIdentify seizure activity, could help to identify delirium
ANA; if justified clinically also RF, anti-SSA, anti-SSB, p-ANCA and c-ANCADetection of CNS vasculitis (ESR can be normal)
Consider LP and CSF analysis, testing for HSV etcIf justified on basis of possible of infective or autoimmune encephalitis
Serum (and ideally CSF) autoantibodies associated with autoimmune encephalitis: most commonly associated with ‘psychiatric’ presentation are Ab to NMDA receptor, VGKC receptor complex proteins (LGI1 and CAsPR2), GABAB receptor and AMPA receptordAutoimmune encephalitis can present without fever, but psychiatric symptoms can be associated with confusion, memory impairment, movement disorder and/or seizures
Catatonia: stupor potentially accompanied by negativism, echopraxia, posturing or flexibilitas care (waxy flexibility; a tendency to remain in an immobile posture)MRIIdentify focal pathology (especially brainstem, diencephalon) or hydrocephalus
Possibly EEGNon-convulsive status
Ensure metabolic disturbance excluded and consider autoantibody testing etc
Cognitive impairment, deranged LFTs, movement disorder and grimacingCaeruloplasmin; examine for Kayser–Fleischer ringsDetection of Wilson’s disease
Clumsiness, weakness, visual changes, speech difficulty and behavioural changesEstablish if immunocompromised (eg organ transplant, corticosteroids, natalizumab)Progressive multifocal encephalopathy
MRIMRI has characteristic changes
CSF testing for JC virus DNA
Cognitive impairment, apathy, agitation, change in gait and incontinence; occasionally suspiciousness and visual hallucinationsExamination of optic fundi for papilloedema; CT or MRI; CSF tap test (if not contraindicated because of concerns about raised intracranial pressure)Consider hydrocephalus
Late-onset psychosis (after 3rd decade) with personality change, disinhibition, executive deficits, semantic memory loss, parkinsonian features or possibly motor weaknessCognitive assessmentCharacteristic deficits of frontotemporal or sematic dementia
MRIIdentify regional atrophy in frontal or temporal regions in keeping with bvFTD or SD
Genetic testing for C9orf72 and potentially other genetic mutations associated with FTD and/or MNDWill require discussion with neurologist and/or geneticist and possibly genetic counselling
Visual hallucinations, parkinsonian featuresDopamine transporter scanExclude Parkinson’s disease and/or Lewy body dementia
Although classically cognitive decline, seizures and stroke-like episodes, there are case reports of presenting as psychosisThyroid peroxidise AbConsider Hashimoto’s encephalopathy; exquisitely steroid responsive encephalopathy
Personality change, possibly with psychotic symptoms; restlessness and incoordination evolving into jerky choreiform movementsFamily history; genetic testingExclude Huntington’s disease
Fatigue, anxiety, depression, possibly psychosis; weight loss, muscle weakness, light-headedness and hyperpigmentationSynacthen testExclude Addison’s disease
Episodic, highly stereotyped symptoms or behaviours with sudden onset and terminationCollateral history: dysphasia, paresis and motor symptomsIctal phenomena
Episodic confusion without obvious causeEEGNon-convulsive status epilepticus
Cluster of seizures followed by lucid interval and then florid psychosis, often with grandiosity and religious preoccupationsEstablish diagnosis of epilepsy; EEG to exclude ongoing seizure activityPost-ictal psychosis
Episodic delusions, hallucinations, mood disturbance, agitation and/or restlessness; abdominal pain, urinary symptoms, peripheral neuropathy and seizuresFamily history; urinary testing for porphobilinogen; genetic testingIntermittent porphyria
Episodes of daytime sleep associated with visual hallucinationsMultiple sleep latency test; HLA typing; CSF hypocretin levelsExclude narcolepsy
  • aThis list of investigations is neither exhaustive nor mandatory; it is intended as loose guidance and to prompt consideration of rarer conditions if suggested by the totality of the presentation.

  • bMore-specialist or invasive investigation (eg EEG, LP or genetic testing) will normally be undertaken after discussion with neurologists or other relevant specialists.

  • cApyrexial cases of HSV encephalitis are recognised.

  • dCertain limbic encephalitides are particularly likely to have ‘psychiatric’ presentations. Classic presentations are as follows: (i) NMDA receptor antibody: female predominance; irritability and insomnia progressing to paranoia, delusions and hallucinations, followed by speech dysfunction, dyskinesias, memory deficits, autonomic instability, and a decrease in the level of consciousness. Seizures can occur at any time during the disease, but tend to occur earlier in males; and (ii) Anti-LGI1 encephalitis (voltage-gated potassium channel antibody group): amnesia and confusion, seizures, movement disorders, sleep disorders; Hyponatraemia and faciobrachial dystonic seizures are particularly associated with both these antibodies. The decision to treat will generally need to be made before antibody test results are available. Autoimmune encephalitis is suggested by subacute onset of memory deficits, psychiatric symptoms or altered consciousness and at least one of new focal CNS findings, seizures not explained by a previously known seizure disorder, CSF pleocytosis (white blood cell count of more than five cells per mm³), or MRI features suggestive of encephalitis.12 Ab = antibody; ANA = antinuclear antibody; p/c-ANCA = perinuclear/cytoplasmic antineutrophil cytoplasmic autoantibodies; BP = blood pressure; bvFTD = behavioural variant frontotemporal dementia; CNS = central nervous system; CPK = creatine phosphokinase; CSF = cerebrospinal fluid; CT = computed tomography; EEG = electroencephalography; ESR = erythrocyte sedimentation rate; FTD = frontotemporal dementia; GGT = Gamma-glutamyltransferase; HLA = human leukocyte antigen; HSV = herpes simplex virus; LP = lumbar puncture; LFT = liver function test; MND = motor neurone disease; MRI = magnetic resonance imaging; NMS = neuroleptic malignant syndrome; RF = rheumatoid factor; SSA/B = anti-Sjögren’s syndrome A/B