Investigation

The list shown in Box 4.4 is a guideline of suggested first-and second-line investigations for identifying the physical agent(s) responsible for delirium in an individual patient. The choice of investigations ordered will obviously be dictated by the findings on history taking and examination. For instance, a cranial computed tomography (CT) scan or magnetic resonance imaging (MRI) is a first-line investigation if neurological signs are present or the history or examination suggests head trauma.74 If, after initial investigation, no cause can be found for the delirium, it may then be appropriate to run a full test screen, given the serious nature of the untreated condition. In so doing one may detect uncommon presentations of relatively common diseases, such as systemic lupus erythematosus. Even after thorough investigation, some patients remain without an identified cause for their disorder. In such cases, it may be necessary to reconsider the diagnosis.

Although the process of physical investigation is successful in most cases in identifying the causes of the disorder once delirium has been diagnosed, it is of strictly limited value in confirming the diagnosis itself. Only EEG may be helpful in this respect.75 In delirium not associated with psychoactive substance misuse, the EEG usually shows evidence of generalised slowing of background activity. In delirium associated with psychoactive substance misuse, for example alcohol or hypnotic/anxiolytic withdrawal, the EEG usually shows an excess of low amplitude fast wave activity. The limited utility of the EEG as a diagnostic aid in delirium is related to its lack of specificity, although claims have been made to the contrary.30 The EEG often cannot enable delirium to be differentiated from dementia, as both Alzheimer's disease and multi-infarct dementia (which together account for about 90% of all dementias) are associated with a pattern of generalised slowing of the background activity similar to that seen in delirium not associated with psychoactive substance misuse.76

Box 4.4 Physical investigations of delirium

First line

Second line

Full blood picture

Serum folate, vitamin B12

Erythrocyte sedimentation rate

Syphilis serology

Electrolytes, urea

Lumbar puncture

Liver function

Urinary illicit drug screen

Thyroid function

HIV antibodies

Blood glucose

Cardiac enzymes

Urine analysis and culture

Blood gases

EEG

Autoantibody screen

ECG

Blood cultures

Chest radiograph

Urinary porphyrins

Calcium, phosphate

Cranial CT scan or MRI

Differential diagnosis

In uncomplicated dementia, an early feature is poor short term memory in the absence of attentional deficits. This reflects the early involvement of the medial temporal lobe in the commonest form of dementia, Alzheimer's disease.77 This contrasts with delirium where attention impairment is a cardinal feature. In Alzheimer's dementia, long term memory only becomes affected after the progression of the disease over months to years. In severe delirium both short term and long term memory become impaired within hours of the disorder developing.

Dementia is usually associated with an insidious onset over many months. In delirium onset is usually sudden.35 In both conditions the patient's memory will be impaired. They will therefore be unable to give reliable information about onset. A reliable corroborative history from an informant, whenever possible, is invaluable. This is vital in differentiating delirium from severe dementia, due to the large overlap in symptoms between the two syndromes.

In Alzheimer's dementia, symptoms are more stable in nature than in delirium, where fluctuations in intensity are typical. Repeated bedside testing of cognitive state can reveal these fluctuations. Ward nurses, who have more prolonged contact with the patient, are a useful source of information about this feature.

The presence of dementia is a major vulnerability factor for the development of delirium. It is therefore not surprising that the two conditions can present in the same patient. This cooccurrence typically presents with a far greater deterioration in mental state over a shorter period of time than is usual for the dementia sufferer. If this is reported by an informant, the development of delirium in addition to dementia must be suspected.

The differential diagnosis of some forms of dementia can be difficult and may require expert psychiatric assessment. The dementia from Lewy body disease is a particular diagnostic problem with potentially fatal consequences. The symptoms of this dementia can closely resemble those of delirium. They include fluctuations in cognitive state, visual hallucinations, and paranoid delusions.13 No causes of the delirium-like state are found on investigation. There is usually also a Parkinsonian-like syndrome present, with prominent extrapyramidal symptoms present before exposure to neuroleptics.78 If neuroleptics have already been used there is a marked sensitivity to them. This sensitivity can be so severe at times that it can have fatal consequences.79 Therefore if in doubt, seek expert advice from an old age psychiatrist.

Patients with schizophrenia can present with symptoms similar to delirium. These include incoherent speech, delusions, and hallucinations. All these symptoms are more fragmentary and fluctuant in delirium. In schizophrenia, delusions are relatively stable over time and are often part of an elaborate system of abnormal beliefs. In delirium hallucinations are usually visual. In schizophrenia auditory hallucinations are much more common.

Unlike in delirium, the attention and memory of most patients with schizophrenia is relatively unimpaired. Unfortunately, patients may be so agitated that assessment of cognition is not possible. In such situations, the importance of physical examination and investigation cannot be overstressed. In some cases, this is only possible after the patient has been sedated. Care is necessary to avoid oversedation of a possibly delirious patient, with the risk of worsening of the condition.

Variants of schizophrenia can on occasions exhibit signs of altered consciousness80 or disorientation.81 These disorders include acute and transient psychotic disorders (ICD10)7 and postnatal psychosis. If there is any diagnostic uncertainty, the EEG can be particularly useful in differentiating these conditions from delirium.33 "Functional" psychoses do not show slow wave activity typical of delirium.

In mood disorders such as mania, the patient may be overactive, behaviourally disturbed, and unamenable to psychiatric examination. "Confusion"82 and transient global cognitive dysfunction83,84 have been reported in mania. Visual hallucinations may be present in a substantial proportion of manic patients.85 The mood state in mania, particularly in the acute stages, may be predominantly irritable as opposed to elevated or expansive, further complicating the picture.

Delirium, particularly the quieter "hypoactive form", may be mistaken for depression. Depression, however, tends to have a much slower onset, developing over weeks. The cognitive abnormalities associated with depressive disorder are usually more suggestive of dementia ("depressive pseudodementia").86

Dissociative disorders are uncommon but may be associated with impaired conscious awareness (fugue) or memory (amnesia). Mixed pictures may occur. The characteristic course of these disorders is of sudden onset, short course, and sudden termination. They may therefore be mistaken at first for delirium. In dissociative states, however, the disturbance of consciousness is often associated with a loss of sense of personal identity, which is rare in delirium. Likewise, amnesia tends to be relatively circumscribed to episodic (past personal) memory, with semantic (past impersonal) memory remaining relatively intact.87 Such a picture is not seen in delirium. In many cases of dissociative disorder a psychosocial stressor may be identified, which may have meaningful connections with an event in the patient's distant past.

Diagnostic uncertainty can be caused by dementia, schizophrenia, and the mood disorders. More harm is possible if delirium is mistaken for another psychiatric condition than vice versa. A sensible approach in this situation is to assume a patient has delirium and manage appropriately, until it is proved otherwise.88 Finding out that a patient has a previous psychiatric history is not sufficient information for a diagnosis of delirium to be ruled out. Patients with psychiatric conditions can neglect themselves, putting them at risk of developing conditions that can produce delirium. They also tend to be on the very medications that have the highest potential for producing delirium - psychoactive medications with anticholinergic properties.33

The diagnostic process in delirium is identical to that for any other medical condition. A careful history, examination, and investigation should result in the clinician identifying the syndrome and its causes. Where the diagnosis is in doubt, the responsible medical or surgical team should have access to a psychiatrist with expertise in diagnosis of the condition.5 Referral should be made at an early stage. It is extremely helpful for the psychiatrist to have access to a nurse who has worked with the patient, an informant who can provide a reliable history, and the results of investigations. If a clinical diagnosis of delirium is made, the liaison psychiatrist should advise on investigation and management, including legal questions of consent.

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