When psychiatric symptoms reflect medical conditions

Think delirium

In medical inpatients, delirium is the cause of mental-state disturbance until proved otherwise. However, it is often missed and its pleomorphic presentations overlooked completely or mistaken as a psychosis. In its most florid hyperactive form (of which delirium tremens is the archetype), patients are agitated, hallucinating and experiencing persecutory delusions. This can be mistaken for schizophrenia or, because sleep disturbance can be prominent, even mania. However, hypoactive delirium is in fact the more common presentation; these patients often go undetected, or lethargy and psychomotor retardation confused for the avolition and withdrawal of severe depression.⁶

Misdiagnosis can be avoided if it is remembered that delirium is characterised by an abrupt onset, altered conscious level and fluctuating course, features that also distinguish it from dementia. Impaired attention, with associated disorientation, is the key clinical finding. It can be identified through simple bedside tests. At a minimum, one should formally test orientation to time and place and sustained attention, with serial seven subtractions or months of the year backwards being useful tests of the latter. Additional disturbances in cognition (particularly memory, executive and visuospatial functions) are also often present, thinking is muddled, sleep fragmented, and perceptual disturbances, especially illusions and visual hallucinations, can occur. There are many validated screening tools (eg the 4AT, www.the4at.com) and they should be more widely used. Patients with schizophreniform or manic psychosis are generally orientated and have preserved recent memory (Table 1). Although often distractible, they will not have the gross attentional disturbance of delirium. In ‘psychiatric’ conditions, hallucinations are usually auditory rather than visual. Causes of delirium that are commonly missed are detailed in Table 2. Although it relies on expert interpretation, electroencephalography can be used to distinguish metabolic and other systemic disorders from intracranial pathologies, and provide useful evidence of delirium in challenging cases.^7,8

The treatment priority in delirium is identifying and addressing precipitants and maintaining factors. Multifactorial causation is the norm, meaning that consideration of potential contributors should continue even after a putative precipitant is identified. The threshold for developing delirium in compromised brains (be it because of age, dementia, multiple sclerosis, Parkinson’s disease, or traumatic brain injury) is reduced. If very vulnerable, relevant precipitants (such as sleep disturbance, hunger or simply being in a strange environment) can appear trivial. This undermines the argument ‘it can’t be delirium because they are not unwell enough’.

Adequate history, neurological exam and cognitive assessment

Psychiatric symptoms reflect brain dysfunction. When consequent to medical and/or neurological conditions, additional evidence of nervous system dysfunction is likely; this can manifest as motor (eg dysarthria or altered gait), sensory (eg visual field deficits or peripheral neuropathy), cognitive or language disturbance. Given that the ability of the patient to provide a reliable history could be compromised, collateral history should complement the physical, neurological and cognitive examination. This can also identify symptoms that patients are unaware of or reluctant to reveal; examples include the apathy and social inappropriateness accompanying degenerative conditions, such as frontotemporal dementia (FTD), episodes of unresponsiveness with muscle twitching suggestive of complex partial seizures, substance misuse, or the social withdrawal and bizarre preoccupations of a guarded patient developing schizophrenia. Extrapyramidal side effects (ie rigidity or tremor) are common in patients treated with antipsychotic medication, but localising neurological signs are not in keeping with a psychiatric diagnosis and imaging is indicated. Global or focal cognitive deficits might be apparent from patient or informant history, but might only be elicited by formal assessment (eg naming difficulties in semantic dementia or difficulty reading in posterior cortical atrophy). The Addenbrookes Cognitive Examination Version III provides a brief but impressively comprehensive means to do this, and it (or an equivalent) should be undertaken in all patients in whom cerebral pathology is suspected. It is available online along with guidance for use.⁹ Drug screens are important, but will not detect novel psychoactive substances.

Abnormal findings overlooked

When medical pathology is missed, case review often highlights clues that were there, but overlooked once it was decided that the presentation was psychiatric. Classic examples are pulmonary embolism attributed to a panic attack or co-occurring psychosis and movement disorder not prompting consideration of Huntington’s disease. It is of course the case that patients with psychiatric conditions can have abnormal findings on physical or laboratory investigation that would not justify an ‘organic’ diagnosis. Examples include sympathetic overactivity and hyperreflexia in anxiety or mildly elevated C-reactive protein (CRP) in depression. It is often prudent to recheck such markers, with reassurance provided when they settle as expected (eg tachycardia normalising when a panic attack resolves).

Be cognisant of how psychiatric disorders present

Just because a presentation is odd does not make it psychiatric. If in doubt, ask a psychiatrist because they are usually best placed to judge whether a presentation is indeed compatible with a psychiatric syndrome (but see Table 1); useful features include psychiatric conditions generally having an insidious rather than acute onset (although mania can be subacute) and tending to exhibit some consistency in dominant symptoms (rather than the fleeting and changeable symptoms of delirium). Schizophrenia and bipolar affective disorder usually first present in adolescence and/or young adulthood, being less likely explanations for new-onset psychotic symptoms in later life. Psychotic depression can first present at older ages; hallucinations and delusions are mood congruent, and generally focused on guilt, death and decay. Concrete guidance on who to refer to psychiatric and/or liaison psychiatry services is difficult to provide. However, it is the case that, as well as assisting with diagnostic clarity, psychiatric input is also often helpful in advising on management of agitation, risk management, capacity issues, and when use of the mental health act is indicated.

Basic screening

Although over investigation is to be discouraged, basic screening should be undertaken in all cases of suspected psychiatric illness. As well as mental state, physical, neurological and cognitive exams, this will always include basic laboratory investigates (Table 2). Although scanning of all patients is not justified,¹⁰ imaging should be undertaken if the presentation is atypical for psychiatric illness or there are other ‘red flags’ (Table 3). Ordering of other investigations should be determined by individual presentations rather than by protocols, but guidance for investigation of some potential differential diagnoses are detailed in Table 4.

Limbic encephalitis and other recently characterised conditions in which psychiatric symptoms are prominent

Over the past decade, it has been recognised that various presentations can arise consequent to antibodies directed at neuronal cell surface antibodies that particularly target the limbic system. Although originally identified as paraneoplastic phenomena, it is now recognised that limbic encephalitis can arise in the absence of malignancy, often in young women. Most closely associated with psychiatric presentations is N-methyl-D-aspartate (NMDA) receptor antibody encephalitis, the early manifestations of which are often anxiety, dramatic expressions of distress (seeming ‘hysterical’), affective disturbance and psychosis. Delirium, seizures and severe autonomic disturbance can then supervene, although the range of presentation is wide. Other syndromes relating to other autoantibodies are increasingly recognised (Table 4).

These diagnoses should always be considered in the presence of movement disorder, seizures, prominent cognitive impairment, autonomic disturbance or treatment resistance. In many such cases, viral encephalitis will have already been a consideration and have prompted lumbar puncture (LP) and cerebrospinal fluid (CSF) analysis. However, it is conceivable that, in time, screening for these autoimmune conditions will be extended to all first presentations of psychosis. Diagnosis is based on detection of the relevant autoantibodies (presence in CSF being more specific than in serum), imaging (although magnetic resonance imaging [MRI] can be normal) and clinical judgement. Treatment centres on immunosuppression, supportive care and the exclusion and/or identification and treatment of any underlying tumour.

Limbic encephalitis is also a potential differential diagnosis in older first-presentations of psychosis, when an underlying malignancy is more likely. As age increases, the possibility that psychosis is consequent to an underlying neurodegenerative condition also increases. Visual hallucinations can suggest Lewy body dementia, which, given its fluctuating presentation, is easily mistaken for delirium. However, it is also increasingly recognised that certain genetic mutations giving rise to FTD can initially present with psychosis, which can take the more typically ‘psychiatric’ form of persecutory delusions and auditory hallucinations. The classic association is with the C9orf72 mutation (which can be tested for);¹¹ one would expect poor performance on cognitive tests tapping into executive function (eg letter fluency), a collateral history of disinhibition and personality change, and an MRI scan showing localised frontal atrophy.