Differentiation of a 'primary' psychotic illness from one secondary to an organic condition may arise in essentially two situations:
• a person with a clear-cut diagnosis of a medical or neurological syndrome in which psychosis is a recognized complication (e.g. epilepsy)
• a person with a presumptive diagnosis of schizophrenia in whom significant abnormalities are detected usually following special investigation (e.g. CT brain scanning).
The list of medical conditions that could potentially give rise to psychosis is enormous. These have been the subject of extensive reviews. (23,24) While it appears that almost any disease that causes a cerebral perturbation can give rise to psychosis, abnormalities affecting the temporal lobes and diencephalon are somewhat more likely to do this.
The time course is obviously important in this context. Chronic inflammatory lesions (e.g. sarcoidosis), degenerative disorders (e.g. presenile dementias), chronic infections (e.g. neurosyphilis, AIDS), space-occupying lesions (e.g. tumour or abscesses), metabolic disorders (e.g. hyper- or hypothyroidism and vitamin deficiencies) may mimic schizophrenia by virtue of a gradual deterioration in social functioning and self-care punctuated perhaps by odd or inexplicable behaviour and rarely hallucinations and delusions. The features of the primary disease are usually evident. Rarer conditions may be misdiagnosed, for example, Wilson's disease (hepatolenticular degeneration). This usually presents with a motor disorder with bulbar features and abnormal liver function, but personality changes and psychotic symptoms are also associated. Diagnosis is made on other associated clinical features (e.g. Kayser-Fleischer rings), copper studies, and liver biopsy. Huntington's disease is characterized by chorea and cognitive decline. Affective disorder and occasionally psychotic symptoms may occur. The main differential diagnosis is with patients with chronic psychosis and tardive dyskinesia and is usually clarified by the family history, inexorable progression, and caudate atrophy on CT or MRI. Neurosyphilis is still encountered from time to time and in the 'general paralysis of the insane' form, may present with chronic delusions (often grandiose) plus dementia. Diagnosis is by appropriate serological testing of blood and cerebrospinal fluid. Finally, metachromatic leukodystrophy, a rare inherited progressive demyelinating condition, has recently been identified as a cause of a schizophrenia-like psychosis, when onset is in childhood or early adult life. (25) Arylsulphatase-A is a diagnostic marker detectable in peripheral white blood cells.
Acute disturbances following head trauma, acute infections (viral encephalitis), cerebrovascular accidents, metabolic abnormalities (e.g. electrolyte disturbances, porphyria), or drug intoxication or withdrawal (including prescribed medication) (see below) may present with a florid psychotic picture, classically dominated by visual distortions or hallucinations and fluctuating levels of alertness, rather than the stereotyped auditory hallucinations in clear consciousness which are characteristic of schizophrenia/26.*
In practice there are few common conditions that ever give rise to real diagnostic uncertainty. The most important is epilepsy. It is well established that epilepsy, particularly focal (complex partial or 'temporal lobe epilepsy') can give rise to psychosis and there are inter-ictal and post-ictal patterns (see Chapteri5:.3.3). A survey from a large neurology clinic showed that the incidence of schizophrenia is about nine times that of the rest of the population. (2.Z*
Inter-ictal psychoses include the chronic schizophrenia-like psychoses described by Slater et a/.,(28) and Trimble/29* These almost always arise in people with many years of well-established temporal lobe seizures, while the post-ictal variety occurs earlier in the lifecycle but again in a person with previously diagnosed epilepsy. In post-ictal psychosis the temporal relationship to seizures, sometimes occurring in a cluster, is diagnostic, although a lucid interval is often observed. A clear history and independent description of seizures is the foundation of a diagnosis of epilepsy, with EEG confirmation. Resting EEGs show slight and subtle abnormalities in a substantial minority of patients with schizophrenia which may be accentuated by neuroleptic medication. As such, the EEG may be of limited value in differential diagnosis unless pronounced slowing or frank seizure activity is picked up. (See also Chapter 5:3:3.)
Symptoms of schizophrenic psychosis in relative isolation may give rise to diagnostic difficulties.
Auditory hallucinations may occur in alcoholic hallucinosis (see below and Chapiei.^.^.^...^). Hallucinations in the context of dissociation (voices representing figures from the patients past or embodiments of aspects of their personality) must also be distinguished from typical schizophrenic hallucinations. These are often multimodal. Pure auditory hallucinations in organic conditions including epilepsy in the absence of other psychotic features are surprisingly rare.
Certain forms of delusion suggest alternative diagnoses. Transient ill-formed but usually paranoid delusions occur in the context of confusion, memory impairment, or dementia (i.e. things going missing, strange people loitering). Delusions of misidentification are particularly associated with organic illness such as dementia or stroke.
Thought disorder may be confused with a fluent aphasia following stroke or cerebral tumours.
Personality deterioration and inappropriate or disinhibited behaviour can occur in many organic conditions in the absence of overt psychotic features. Isolated frontal lesions may cause diagnostic problems since general cognitive impairments may be absent. The widespread availability of CT and MRI in the more developed world has reduced the likelihood of such patients being misdiagnosed.
A small proportion (approximately 5 per cent) of prevalent and incident cases of schizophrenia, if investigated thoroughly, are found to have a variety of 'organic' conditions which may contribute to the illness.(30) These include metabolic abnormalities, cerebral tumours, multisystem autoimmune disease, cerebrovascular disease, etc. Some of these may be incidental; others may have precipitated the psychosis. The range of diseases counts against any specific aetiological mechanism. Similarly, the phenomenology found in such 'organic' patients is usually indistinguishable from their 'functional' counterparts. (31>
Thanks to increased application of non-invasive neuroimaging techniques to psychiatric patients, particularly those with schizophrenia, another class of organic abnormalities have been noted, namely cerebral anomalies which are often congenital. These include agenesis of the corpus callosum, cavum septum pellucidum, aqueduct stenosis, etc. Again, it is difficult to know how often such findings occur in the normal population and are asymptomatic, although the widespread use of MRI for 'minor' complaints such as mild head injury and headache is uncovering such anomalies. The examples above certainly appear to be associated with psychiatric disorders in general more than would be expected by chance. They tend to be associated with below-average IQ and other neurological problems (epilepsy in the cases of callosal agenesis).(32)
Other factors to be taken into account in the differential diagnosis from organic conditions include the presence of a family history of schizophrenia, and abnormal premorbid personality, both of which weight aetiological judgement in favour of the functional diagnosis. This applies to the psychoses of epilepsy and those related to drug abuse especially. 'Secondary' schizophrenias also tend to have less pervasive effects on the person's personality. Treatment is again based on symptoms with the added complication that neuroleptic drugs lower the epileptic seizure threshold, and will tend to worsen extrapyramidal symptoms in patients with primary movement disorders. Treatment of the primary condition (if this has remained undiagnosed for some time) may be disappointing but should always be attempted especially in the case of chronic infections. Reversal of metabolic abnormalities, even long-standing, can lead to dramatic improvements in the mental state.
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