Psychiatric Symptoms as Manifestations of Underlying Diseases: Diagnostic Challenges

Numerous clinical or neurological disorders can produce alterations in mental status, that is, they can be disguised as psychiatric syndromes.

This article provides guidance to help clinicians identify when altered mental status is due to an underlying clinical or neurological problem. The authors focus on the manifestations of agitation, emotional disturbance or psychotic symptoms, but without providing an exhaustive list of differential medical diagnoses.

Instead, the general approach to these cases is summarized and it is highlighted when doctors should be especially attentive to possible underlying diseases. The authors also do not analyze the poor medical care that psychiatric patients receive.

The statistics are shocking: major psychiatric disorder is associated with a reduced life expectancy of 10–15 years . Excess mortality is predominantly attributed to clinical diseases.

While the medical care of patients with mental illness in general hospitals has recently received increased attention, this moral emergency deserves its own article.

When the medical causes of altered mental status are ignored, the consequences can be catastrophic because the underlying illness is not treated.

Data on how often this happens is limited, but Johnson’s case series reporting that 12% of consecutive psychiatric hospitalizations suffered from some previously unidentified physical illness remains a convenient lesson.

In the absence of reliable data it is reasonable to resort to clinical experience, which suggests that the following points are essential to prevent misattribution of symptoms to psychiatric etiology.

• Think about delirium

In hospitalized patients, delirium is the cause of altered mental status until proven otherwise. However, it is often overlooked and its polymorphic manifestations are not given importance or are confused with a psychosis.

In its most florid, hyperactive form (of which delirium tremens is the archetype), patients are excited, hallucinate, and experience persecutory delirium.

It can be confused with schizophrenia or, because sleep disorders can be prominent, even with mania. However, hypoactive delirium is the most common initial manifestation; These patients often go undetected or the lethargy and psychomotor retardation are confused with the apathy and withdrawal of severe depression.

Misdiagnosis can be avoided by remembering that delirium is characterized by its abrupt onset, altered level of consciousness, and fluctuating course, characteristics that also distinguish it from dementia. Deterioration of attention, associated with disorientation, is the main clinical finding. It can be identified through simple tests at the patient’s bedside.

At a minimum, orientation in time and space and sustained attention should be formally examined. The latter can be examined by asking the patient to count in sevens, from 100 to 1, or to name the months of the year backwards and forwards. Other cognitive disorders (especially memory, executive and visuospatial functions) can often be found.

Thinking is confused, sleep is fragmented, and there may be perceptual disorders, especially visual hallucinations. There are numerous validated screening tools (e.g. 4AT, www.the4at.com) and they should be used more frequently.

Patients with schizophreniform or manic psychosis are generally well oriented and retain recent memory. Although they are easily distracted, they do not have the major disturbance in attention typical of delirium.

In ’psychiatric’ disorders, hallucinations are generally more auditory than visual.

Causes of delirium that often go unnoticed are detailed in Table 1 . Although interpretation by a specialist is necessary, the electroencephalogram can be used to distinguish metabolic disorders and other systemic diseases from endocranial pathologies.

Table 1. Causes of delirium that may go unnoticed

The therapeutic priority in delirium is to identify and treat the factors that trigger and maintain delirium. The etiology is usually multifactorial, meaning that consideration of potential contributing factors should continue even after the potential trigger has been identified.

The threshold for the onset of delirium is lower in brains that have deteriorated, whether due to age, dementia, multiple sclerosis, Parkinson’s disease, or head trauma.

If the patient is very vulnerable, the triggers (such as sleep disturbance, hunger, or being in an unfamiliar environment) may seem trivial. In other words, the reasoning that ’it can’t be delirium because it’s not bad enough’ is not correct.

> Appropriate history, neurological examination and cognitive evaluation

Psychiatric symptoms reflect brain dysfunction. When they are caused by clinical or neurological diseases, it is likely to find more evidence of nervous system dysfunction, which can manifest as a motor alteration (dysarthria or gait disturbance), sensory alteration (visual field defects or peripheral neuropathy), cognitive or of language.

Because the patient’s ability to provide a reliable history may be impaired, close family members should also be questioned in addition to the physical, neurological, and cognitive examination.

In this way, symptoms that the patient is not aware of or do not want to reveal can be identified; such as the apathy and social inadequacy that accompany degenerative diseases, such as frontotemporal dementia or episodes of unconsciousness with muscle jerks suggesting complex partial seizures, substance abuse, or the social withdrawal and strange preoccupations of the patient with schizophrenia.

Extrapyramidal side effects (rigidity or tremor) are common in patients treated with antipsychotic medications, but focal neurological signs do not correspond to a psychiatric diagnosis and imaging studies should be performed.

Global or focal cognitive deficits may be apparent in the patient or in the history of the reporting family member, but may only be obtained with formal evaluation (e.g., difficulties naming objects or people in semantic dementia or difficulty reading in atrophy). posterior cortex).

The Addenbrookes Cognitive Examination Version III is a brief but comprehensive means of this and should be used (or an equivalent) for all patients with suspected brain pathology. It can be found online along with a guide to its use. Drug investigation is important.

> Underestimated pathological data

When pathology is missed, case review often detects clues that were present but were ignored once the manifestations were decided to be psychiatric.

Classic examples are pulmonary embolism, whose manifestations are attributed to a panic attack or concomitant psychosis, and movement disorder in which Huntington’s disease is not considered.

Likewise, patients with psychiatric disorders may have pathological data on physical examination or analysis, but which do not justify an ’organic’ diagnosis.

Examples are sympathetic overactivity and hyperreflexia in anxiety or a slight increase in C-reactive protein (CRP) in depression. It is prudent to double check these markers.

> Know how psychiatric disorders manifest

Just because the symptoms are strange does not make them psychiatric.

If doubts persist, consult a psychiatrist, who will be able to judge whether the symptoms are compatible with a psychiatric syndrome. Psychiatric disorders are generally insidious in onset and have some constancy in their dominant symptoms, rather than the fleeting and changing symptoms of delirium.

Schizophrenia and bipolar affective disorder generally appear in adolescents or young adults and are less likely at later ages.

Psychotic depression may first appear at an older age; hallucinations and delusions are consistent with the mood and generally focused on guilt, decay, and death.

In these cases psychiatric input, in addition to helping with diagnosis, is useful in advising on the treatment of agitation, risk, capacity issues, and when the use of mental illness legislation is indicated.

> Basic research

It is necessary to carry out a basic investigation in all cases in which psychiatric illness is suspected. In addition to the mental status and physical, neurological and cognitive examinations, basic analyzes will always be included.

Imaging studies are not warranted in all patients, but should be performed if the clinical manifestations are atypical for psychiatric illness or if there are other warning signs ( Table 2 ).

Table 2. Situations in which it is essential to perform imaging studies

> Limbic encephalitis and other recently characterized diseases where psychiatric symptoms are predominant

In the last decade it was recognized that various manifestations can arise due to antibodies directed against surface antigens of neurons that act especially on the limbic system. Although initially considered paraneoplastic phenomena, it is now recognized that limbic encephalitis can arise in the absence of malignant disease, often in young women.

The disease most closely related to psychiatric symptoms is encephalitis due to antibodies against N-methyl-D-aspartate (NMDA) receptors, whose initial manifestations are frequently anxiety, dramatic expressions of distress, affective disturbances, and psychosis. Afterwards, seizures and major alterations of the autonomic nervous system may appear.

Syndromes related to other autoantibodies are increasingly recognized. These diagnoses should always be taken into account in case of movement disorders, seizures, significant cognitive alterations, autonomic problems or resistance to treatment. It could be that over time the systematic screening for these autoimmune disorders will be extended to all the first manifestations of psychosis.

The diagnosis is based on the detection of autoantibodies (their presence in cerebrospinal fluid is more specific than in blood), imaging studies (although MRI may be normal) and clinical judgment. Treatment focuses on immunosuppression, supportive care, and exclusion or identification and treatment of any underlying tumor.

Limbic encephalitis is also a possible differential diagnosis in the first manifestations of psychosis in the elderly, when a malignant tumor is more likely. As age increases, the possibility that psychosis is due to a neurodegenerative disease also increases.

Visual hallucinations may suggest Lewy body dementia, which may be easily confused with delirium.

Likewise, it is increasingly recognized that certain genetic mutations that cause frontotemporal dementia may initially manifest with psychosis, especially persecutory delusions and auditory hallucinations.

The classic association is with the C9orf72 mutation (for which there is a detection method); Poor performance on cognitive tests, a history of disinhibition and personality change, and an MRI showing localized frontal atrophy can be expected.

This article focused on cases in which psychiatric symptoms arise from diseases that are already existing and detectable with a reasonable index of suspicion. However, there will always be some cases in which only time will reveal that an underlying pathophysiological process produced psychiatric symptoms initially, before other manifestations.

These cases point to the importance of willingness to reexamine diagnoses if clinical manifestations change and unexpected symptoms appear. Likewise, symptoms highly suggestive of an ’organic’ basis (rapid onset, disorientation, or fluctuating symptoms) may appear following psychological distress, sleep deprivation, or sensory deprivation in the context of a ’normal’ brain.

Sometimes, only time and an open mind on the part of psychiatrists and clinicians will allow for a clear diagnosis.