Psychopharmacology: Organic Psychiatry

B. Delirium tremens

Delirium tremens (B) is a syndrome caused by alcohol withdrawal in patients with a long history of alcohol consumption, or more likely alcohol dependence. It is a medical emergency and is characterized by autonomic instability, nausea and vomiting, altered mental state (‘delirium’), tremor

(‘tremens’), and sometimes seizures. The first symptoms usually appear within 6–12 hours of the last drink and peak at around 24–48 hours.

Patients may also complain of hallucinations, usually visual, which take the form of seeing small insects. Note, this is not the same as formication, which technically is the physical sensation of feeling insects crawling over one’s skin. This is commonly seen in cocaine intoxication, but rarely can also be seen in cocaine withdrawal (C). However, cocaine withdrawal is not usually associated with autonomic instability or fitting. Alcoholic hallucinosis (A) is a syndrome also caused by withdrawal from alcohol in those dependent on it. Hallucinosis can also occur in those that continue to drink, although this is rarer. Alcoholic hallucinosis is sometimes taken to mean a relatively rare condition where verbal auditory hallucinations occur alone and in clear consciousness, and is often mistaken for schizophrenia. Whichever definition is taken, the presence of autonomic instability and fits would rule out alcoholic hallucinosis. Diabetic ketoacidosis (D) may present with confusion, although sweating would be uncommon. Patients may complain of severe thirst, and possibly chest or abdominal pain. On examination, patients will appear dehydrated and may have a distinctive smell of ketones on the breath. Fits would be relatively uncommon compared to a decreased level of consciousness.

Opiate overdose (E) would not present in this way – patients would exhibit respiratory and central nervous system depression.

D. Low serum vitamin B12

This question relates to the likely blood results in chronic alcohol misuse.

Chronic alcohol dependence is associated with vitamin B12 deficiency

(D), both as a result of poor nutritional intake and a direct toxic effect of alcohol on bone marrow. B12 is involved in DNA synthesis and this leads to an impairment in erythrocyte metabolism, resulting in larger cell volumes before they divide. This will be evident on a full blood count with a raised, not lowered, MCV (C). Other effects of alcohol on blood and blood chemistry include a decrease in platelet count, known as thrombocytopenia, as opposed to thrombocytosis (raised platelet count)

(E). This results from both vitamin deficiency (B12/folate) and again a direct toxic effect of alcohol. The low platelet count is not usually symptomatic. Alcohol is also generally associated with hypoglycaemia as opposed to hyperglycaemia (A), although the latter can also occur.

Therefore, serum glucose would be less helpful in diagnosing chronic alcohol abuse. Alcohol also causes hypokalaemia as opposed to hyperkalaemia (B). There may be numerous causes for this, such as decreased intake through poor nutrition or vomiting, but it is also thought to occur through decreased tubular reabsorption of potassium secondary to a low magnesium level.

E. Prescribe nothing at this stage

This is a clear case of delirium, or acute confusional state characterized by a recognized causative factor (infection), older age and fluctuating confusion. Acute confusional states are extremely common in medical inpatients (perhaps in the region of 30 per cent of those over 65 in hospital). It is extremely important that it is managed well – while it has traditionally been considered a transient syndrome with no sequelae, there is growing evidence that delirium leads to increased psychiatric and physical morbidity. When managing delirium, the first steps should be conservative (E) unless the patient is putting themselves or others at significant risk of harm. While this scenario is distressing (at least for the nursing staff), there is no evidence that this is the case. Therefore, initially patients should be treated with intensive nursing interventions. These may include nursing the patient in a side room, keeping lighting appropriate to the time of day, repeated reassurance, the use of prominently visible clocks to orient the patient. Only if the patient continues to become very distressed should medication be considered.

A. Prednisolone

Prednisolone (A) is a corticosteroid with numerous uses, including autoimmune and inflammatory disorders. It has long been observed that corticosteroids can cause psychiatric side effects. While this is most commonly thought of as mania (‘steroid psychosis’), they also may cause depressive disorders. Mania is probably more common than depression, but the two may coexist. Depression may result from the acute use, chronic use or discontinuation of corticosteroids. This is thought to be mediated by the hypothalamo-pituitary adrenal axis, which has a complex but undoubted role in the regulation of mood – depression is commonly seen in Cushing’s disease, probably as a direct result of a state of chronic hypercortisolism. Sertraline (B) is a selective serotonin reuptake inhibitor

(SSRI), the most commonly prescribed class of antidepressants. There has been widespread debate about whether SSRIs cause an increase in suicidal thoughts. The NICE guidelines on depression indicate that there may be a small increase in suicidality in the very early stages of antidepressant use

B. Frontal lobe

This man is exhibiting signs consistent with a frontal lobe (B) injury, and more specifically an orbitofrontal insult. The frontal lobe is extremely vulnerable in traumatic brain injury. Frontal lobe syndromes can take many forms, but often involve changes in personality including:

Inappropriate or ‘fatuous’ affect

Lability and irritability of mood

Hypersexuality

Hyperphagia, or overeating

  ‘Childishness’ or prankish joking (known as ‘Witzelsucht’)

There is usually no insight into this change in behaviour. Other changes include poor concentration and ‘forced utilization’ – a strange phenomenon when patients will use objects they see in front of them irrespective of whether they need to use them or not, e.g. patients may get undressed and go to bed on entering a bedroom in the middle of the day despite not being tired. There may also be the emergence of primitive reflexes, such as the grasp reflex.

B. Herpes simplex encephalitis

While there are no pathognomonic features of herpes simplex virus

(HSV) encephalitis (B), the clinical history is strongly suggestive of an encephalitic picture. It is important to have an extremely low threshold for treating presumed HSV encephalitis, in part because if left untreated there is an extremely high (approximately 70 per cent) mortality rate, and the treatment (intravenous aciclovir) is relatively non-toxic. HSV encephalitis nearly always targets the temporal lobes and orbitofrontal structures. This is the most likely explanation for the preponderance of unusual behaviour or psychotic symptoms in the early stages of the illness, as can be seen here. The woman accusing her partner of leaving the gas on is most likely an olfactory hallucination, which are common in temporal lobe disorders. The rapidly advancing neurological signs indicate a generalizing cerebral infection. The

CSF analysis is also typical of viral encephalitis (or meningitis) – showing markedly raised protein, normal or slightly low glucose, a clear appearance and a preponderance of mononuclear cells

A. Hypercalcaemia

Hypercalcaemia (A) is a common complication of squamous cell carcinoma. The likely cause of this is due to the tumour releasing large amounts of parathyroid-related peptide leading to increased bone turnover. There may also be direct bone destruction from tumour invasion.

Hypercalcaemia typically results in the classic syndrome of ‘stones’ (kidney stones), ‘bones’ (bone pain), ‘groans’ (constipation), ‘psychic moans’

(depression, aesthenia, confusion). Thirst is also a common symptom exacerbated by osmotic diuresis, as are nausea, vomiting and anorexia.

If depression is the main presenting feature, it is extremely important to rule out metabolic disturbances in patients with cancer. Do not assume that the depression is a psychological reaction to the diagnosis of cancer

(although of course this is also extremely possible) – hypercalcaemia is very correctable and symptoms will reduce quickly as the calcium level drops.

D. Wilson’s disease

Wilson’s disease (D), also known as hepatolenticular degeneration, is a rare autosomal recessive disorder of copper metabolism. The mutation

(of which there are over 200 described) occurs in a gene on chromosome

13q (designated ATP7B), which encodes for a protein that is responsible for transporting copper for excretion in bile. Dysfunction of this protein therefore leads to copper accumulation in numerous tissues in the body, particularly the liver (causing jaundice) and the nervous system. Another extremely suggestive feature is the presence of Kayser–Fleischer rings, which are greenish-gold or brownish rings in the cornea resulting from copper deposition. Note that Kayser–Fleischer rings are now no longer thought of as purely pathognomonic of Wilson’s disease as they may occur in other disorders such as primary biliary cirrhosis.

Neuropsychiatric consequences of Wilson’s disease include aggression, reckless behaviour, disinhibition and sometimes self-harming behaviours.

There are also prominent neurological symptoms, including the ones detailed above.

C. Depressive symptoms

Depression (C) is extremely common in stroke, with estimates in the literature of a prevalence of either early or late depression at 1/3. This is higher than would be expected as a result of chronic disease alone and suggests some causative mechanism of the disease process itself. Of course, many of the symptoms of stroke may make the diagnosis more difficult

(e.g. apathy, emotional lability, poor concentration). Equally, depression may easily be missed in aphasic patients, who will be particularly at risk because of the added isolation of being unable to communicate. There is of course now growing evidence about the phenomenon of ‘vascular depression’, in which depressive disorders are thought to be directly related to accumulative cerebrovascular disease rather than clinically significant or recognized episodes of stroke. Psychotic disorders, including the experience of delusions (B) or hallucinations (D), have been less studied than depression in stroke patients. However, they are thought to occur in approximately 1–2 per cent of stroke sufferers. In patients with co-morbid dementia, care must be taken when deciding on management of psychosis in stroke given the association of antipsychotics with increased risk of death in these patients. Anxiety symptoms (A) are common, and a generalized anxiety disorder may be seen in up to one-quarter of patients.

Obsessive–compulsive symptoms (E) in stroke have not been particularly well studied, in part because anecdotally they are rare.

A. Around the third ventricle

A The symptoms of amnesia and confabulation are very typical of tumours involving the wall or floor of the third ventricle (A). Structures around this region include the thalamus and hypothalamus, which would also explain the other symptoms of hypersomnia, hyperphagia, pyrexia and polydipsia.

The raised serum osmolality points to cranial diabetes insipidus secondary to tumour effects on the hypothalamus

D. Systemic lupus erythematosus (SLE)

SLE (D) is an autoimmune connective tissue disorder that may affect any organ in the body. It commonly presents in women (9:1 female to male ratio), usually in the third or fourth decades. Neuropsychiatric symptoms may occur at the beginning of the natural course of the disorder, without any seeming involvement of other organ systems. Unexplained psychotic symptoms, which may closely resemble schizophrenia, may occur, as may a dementia-like illness or affective disorders. This woman is also displaying neurological signs, making a diagnosis of a functional psychiatric disorder unlikely. The presence of Parkinsonism, widespread muscle pain, lymphadenopathy and splenomegaly are all consistent with the diagnosis. The ‘malar rash’, which is highly indicative of SLE, is present in this woman but its absence does not negate the diagnosis.

A. Niacin

Nicotinic acid, or niacin, deficiency (A) is also known as pellagra.

It classically manifests with gastrointestinal symptoms, such as diarrhoea, anorexia and gastritis. The dermatological manifestations include symmetrical, bilateral bullous lesions in sun-exposed areas.

The psychiatric symptoms initially manifest as apathy, depression, or irritability. However, in later stages there are more florid symptoms resembling delirium, psychosis or a Korsakoff-like presentation. If identified, treatment with nicotinic acid usually leads to prompt and dramatic improvements in mental state.

D. Rates of suicide are higher in people with epilepsy than people not suffering with epilepsy

Epilepsy has numerous and complex neuropsychiatric and psychological interactions. It is undoubted that rates of suicide are higher in people with epilepsy (D) than the general population. However, the degree of the association is not clear. Similar risk factors appear to exist for suicide in people with epilepsy than in the general population, such as co-morbid psychiatric illness (which is also over-represented in people with epilepsy).

Epilepsy is not usually associated with enduring personality difficulties

(B). Automatisms (A) are unusual and sometimes complex repetitive motor activities observed in nearly all forms of epilepsy, but commonly associated with complex partial seizures (such as temporal lobe epilepsy).

They are nearly always observed during a seizure (ictal) or in the postseizure delirium (post-ictal). Psychotic symptoms are positively correlated with epilepsy (C). This is particularly true of temporal lobe epilepsy, but probably is also over-represented in other types of epilepsy. Temporal lobe epilepsy (E) is associated with psychological and psychiatric symptoms such as aura, sensory disturbances and depersonalization or derealization. Unusual symptoms such as déjà vu or jamais vu may also occur.

D. Pick’s disease is classically associated with personality changes

Pick’s disease (D) is a relatively uncommon dementia, classified as one of the frontotemporal dementias. It commonly presents in the sixth decade of life, e.g. earlier than the typical onset of other neurodegenerative disorders such as Alzheimer’s disease. Because of its predilection for frontal and anterior temporal parts of the brain, it tends to present with changes in behaviour and personality before amnesic symptoms are obvious. This can lead to devastating consequences for those affected and their families. Alzheimer’s disease in younger people ((A) and (B)) is often associated with specific familial inherited genetic mutations. There are numerous mutations, affecting the APP gene on chromosome 21 and the presenelin 1 and 2 genes on chromosomes 14 and 1, respectively.

Alzheimer’s disease is still the major cause of YOD. Down’s syndrome

(C) confers a much greater risk of dementia, with a prevalence estimated at around 50 per cent of those with Down’s syndrome in those aged 60 or above. Prion diseases (E) are certainly a cause of YOD, usually with a rapid clinical course. However, they are still rare, probably accounting for only about 1.5 per cent of the total of cases of YOD.

B. Acute intermittent porphyria

The features described are typical of acute intermittent porphyria (B), a relatively rare autosomal dominant inherited disorder, typically presenting in the second to fourth decades. It is a disorder of haem metabolism resulting in a build up of porphyrins and their precursors.

Attacks are usually precipitated by one of a number of factors, including menstruation, alcohol, poor nutrition and certain drugs, such as the OCP.

Porphyria can often be mistakenly diagnosed as a primary psychiatric disorder. Abdominal pain in any patient with psychiatric symptoms should always prompt further investigation. Acromegaly (A) is a disorder caused by increased growth hormone secretion, usually by a growth hormone-secreting tumour of the pituitary. It would usually present slightly later than adolescence/early adulthood. There are no psychiatric disorders commonly associated with this condition. Diabetic ketoacidosis

(C) could present with abdominal pain but peripheral neuropathy would be unusual in a person of this age. Psychosis itself would also be uncommon, although of course confusion and clouding of consciousness are very highly associated with ketoacidosis. Heroin intoxication (D) would not present in this way. Opiate withdrawal may present with abdominal cramps and muscle aches, but frank weakness and changes in reflexes would be uncommon. Sickle cell anaemia (E) often does present with abdominal crises. However, it would be very rare in a white individual and would normally have presented long before the age of 19.

Vaso-occlusion causes widespread and numerous symptoms, including stroke, but the picture here does not fit that of sickle cell disease.