Investigation of ‘psychiatric’ presentationsa,b
| Indication | Investigation | Rationale |
| Routine screening for first psychiatric presentations | Full 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, temperature | Exclude obvious causes of delirium, increase chances of detection of relevant general medical condition |
| B 12 and folate levels | Reversible causes of dementia; B 12 deficiency can present with psychosis | |
| Localising signs | Imaging (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 seizures | 4-h temperature readings | Assist detection of infection, especially HSV or other viral encephalitis c |
| Imaging, likely MRI | Exclude space-occupying lesion, identify generalised or localised atrophy, vascular damage, oedema and/or inflammation etc | |
| HIV and syphilis serology | Exclude these infectious agents (part of routine screen in some centres) | |
| Consider EEG | Identify seizure activity, could help to identify delirium | |
| ANA; if justified clinically also RF, anti-SSA, anti-SSB, p-ANCA and c-ANCA | Detection of CNS vasculitis (ESR can be normal) | |
| Consider LP and CSF analysis, testing for HSV etc | If 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 receptord | Autoimmune 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) | MRI | Identify focal pathology (especially brainstem, diencephalon) or hydrocephalus |
| Possibly EEG | Non-convulsive status | |
| CPK | NMS | |
| Ensure metabolic disturbance excluded and consider autoantibody testing etc | ||
| Cognitive impairment, deranged LFTs, movement disorder and grimacing | Caeruloplasmin; examine for Kayser–Fleischer rings | Detection of Wilson’s disease |
| Clumsiness, weakness, visual changes, speech difficulty and behavioural changes | Establish if immunocompromised (eg organ transplant, corticosteroids, natalizumab) | Progressive multifocal encephalopathy |
| MRI | MRI has characteristic changes | |
| CSF testing for JC virus DNA | ||
| Cognitive impairment, apathy, agitation, change in gait and incontinence; occasionally suspiciousness and visual hallucinations | Examination 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 weakness | Cognitive assessment | Characteristic deficits of frontotemporal or sematic dementia |
| MRI | Identify 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 MND | Will require discussion with neurologist and/or geneticist and possibly genetic counselling | |
| Visual hallucinations, parkinsonian features | Dopamine transporter scan | Exclude Parkinson’s disease and/or Lewy body dementia |
| Although classically cognitive decline, seizures and stroke-like episodes, there are case reports of presenting as psychosis | Thyroid peroxidise Ab | Consider Hashimoto’s encephalopathy; exquisitely steroid responsive encephalopathy |
| Personality change, possibly with psychotic symptoms; restlessness and incoordination evolving into jerky choreiform movements | Family history; genetic testing | Exclude Huntington’s disease |
| Fatigue, anxiety, depression, possibly psychosis; weight loss, muscle weakness, light-headedness and hyperpigmentation | Synacthen test | Exclude Addison’s disease |
| Episodic, highly stereotyped symptoms or behaviours with sudden onset and termination | Collateral history: dysphasia, paresis and motor symptoms | Ictal phenomena |
| Episodic confusion without obvious cause | EEG | Non-convulsive status epilepticus |
| Cluster of seizures followed by lucid interval and then florid psychosis, often with grandiosity and religious preoccupations | Establish diagnosis of epilepsy; EEG to exclude ongoing seizure activity | Post-ictal psychosis |
| Episodic delusions, hallucinations, mood disturbance, agitation and/or restlessness; abdominal pain, urinary symptoms, peripheral neuropathy and seizures | Family history; urinary testing for porphobilinogen; genetic testing | Intermittent porphyria |
| Episodes of daytime sleep associated with visual hallucinations | Multiple sleep latency test; HLA typing; CSF hypocretin levels | Exclude 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