6 General adult psychiatry6.3 Liaison psychiatry
6.3.3 Psychiatric consequences of brain disease, damage including stroke, and dysfunction
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Written by Resident Doctor Committee · Published
How brain damage produces psychiatric symptoms
Stroke, injury, hypoxia and other brain disease change mood, cognition and behaviour through focal damage or disrupted networks. Frontal-striatal-thalamic circuits explain why a small subcortical lesion can cause marked behavioural change.
Site of damage | Typical result |
|---|---|
Dorsolateral prefrontal | Poor planning, working memory and flexible thinking |
Orbitofrontal | Disinhibition and poor social judgement; social, sexual or financial recklessness despite knowing the rules |
Anterior cingulate | Reduced initiation; akinetic mutism after severe bilateral injury |
Diffuse axonal injury disrupts connections, so processing and attention slow.
Hypoxic hippocampal injury can cause severe amnesia.
Diaschisis is reduced function in connected but uninjured regions, so symptoms can reach beyond the visible lesion.
Lesion location changes the likelihood of a syndrome but does not establish its cause; stroke severity, disability and past psychiatric illness also predict outcome.
Loss of independence and identity adds to distress separately from the direct neurological effects.
Cortical and subcortical dementia
Feature | Subcortical dementia | Cortical dementia |
|---|---|---|
Site | Deep grey matter and frontostriatal circuits | Cortical mantle |
Cognition | Slowed processing, executive difficulty, retrieval-type memory loss | Aphasia, agnosia, apraxia and early failure to encode memories |
Examples | Huntington disease, HIV, late multiple sclerosis | Alzheimer disease |
Subcortical dementia also brings apathy, affective change and motor and gait signs, with no aphasia, apraxia or agnosia.
Assessment and the differential
Timing of neurological events, symptoms and medication changes comes first, with a collateral account of previous personality, cognition and psychiatric illness.
Delirium is suggested by acute fluctuation, inattention and altered arousal, and its physiological causes need urgent treatment.
New deterioration after initial recovery needs investigation for hydrocephalus, subdural haematoma, seizures, hypopituitarism, substance use and depression.
Aphasia can look like disordered thought or mutism, and memory loss with confabulation can distort the history.
Capacity is decision-specific: someone who can repeat information may still be unable to use or weigh it.
Episodic symptoms raise the question of seizures, and epileptic and dissociative seizures can coexist.
Explanation | What points to it |
|---|---|
Direct neurological effect | Timing and a circuit-related pattern such as apathy, disinhibition or emotionalism |
Psychological reaction | Distress about loss or dependence that shifts with news and support |
Medication | Corticosteroids, levetiracetam, topiramate, opioids, anticholinergics or dopamine agonists |
Substance use | Past use, intoxication at injury or the timing of withdrawal |
Primary psychiatric disorder | Previous episodes, family history or a course independent of the injury |
Stroke
Depression after stroke
Depression is the commonest psychiatric complication of stroke, affecting about a third of survivors (31% in pooled studies), ahead of anxiety, emotionalism, mania and trauma responses.
Left anterior lesions, frontal and basal ganglia, carry the highest risk of post-stroke depression.
Vascular depression is a late-life syndrome from small vessel and stroke lesions in frontostriatal circuits.
Vascular depression gives psychomotor slowing, anhedonia, apathy, poor insight and executive dysfunction, but little guilt or tearfulness.
Treating post-stroke depression
Depressive symptoms lasting over a month justify drug treatment.
SSRIs (selective serotonin reuptake inhibitors) such as sertraline and citalopram are the best-evidenced first choice, with fewer contraindications and interactions than tricyclics.
Clopidogrel with an SSRI adds bleeding risk, which is managed with gastroprotection.
Duration: UK stroke guidance advises continuing the antidepressant for at least four months after recovery, in practice four to six months, then withdrawing gradually.
Prophylactic antidepressants have no established role because trial evidence is limited and conflicting; mood is screened and depression treated when it develops.
In the FOCUS trial, fluoxetine 20 mg for six months in 3,127 people did not improve function, reduced depression (13.4% versus 17.2%) and increased fractures (2.9% versus 1.5%).
Apathy, emotionalism and catastrophic reaction
Syndrome | Core feature | Frequency and lesion | Inner mood |
|---|---|---|---|
Depression | Persistent low mood or loss of pleasure, guilt, hopelessness | Commonest | Distressed; the patient often complains |
Apathy without depression | Loss of initiative and interest; needs prompting | About one in five; basal ganglia and frontal-subcortical lesions | No sadness, guilt or pessimism; relatives often complain |
Emotionalism | Sudden uncontrollable crying with minor triggers | 15 to 35% in the first months | Crying does not match inner mood |
Catastrophic reaction | Anger, agitation and tears when asked to do a task the deficit now prevents | Left hemisphere lesions with non-fluent aphasia | Provoked by the task |
Pseudobulbar affect (pathological crying and laughing) is a released motor-emotional reflex rather than a mood disorder, and it responds to SSRIs.
A rapid response to an antidepressant does not establish emotionalism, and a 2022 Cochrane review found only seven small trials.
Apathy is managed with structure and prompting, and reduced initiation should not be read as laziness.
Other psychiatric problems after stroke
Anxiety is common, and fear of recurrence may rise around discharge.
Post-stroke delusions can accompany anosognosia or denial of limb ownership, mainly after right hemisphere damage.
Agitation in post-stroke delirium is treated with short-term low-dose haloperidol once reversible causes and non-drug measures are addressed.
Haloperidol is the first-line drug and the only one licensed in the UK for delirium; benzodiazepines are kept for withdrawal states.
Neurological signs after stroke
Aphasia is localised by fluency, comprehension and repetition.
Sign | Features | Lesion |
|---|---|---|
Fluent aphasia | Fluent paraphasic speech with poor comprehension and repetition | Dominant posterior superior temporal |
Upper motor neuron facial weakness | Forehead and eye closure spared, because the upper face has bilateral corticobulbar input | Hemisphere opposite the weak side |
Spastic gait | Extensor leg tone; circumduction when one side is affected, scissoring when both are | Upper motor neuron |
Hemiballismus | Continuous, forceful, large-amplitude flinging of one limb | Contralateral subthalamic nucleus, usually a small vessel infarct or haemorrhage |
Epilepsy
Mood and suicide
Depression is the commonest psychiatric comorbidity, affecting a third to a half of all people with epilepsy.
Depression affects about a tenth in well-controlled epilepsy, rising to around half in refractory focal epilepsy.
Focal impaired awareness seizures (complex partial, usually temporal lobe) carry a higher depression risk than generalised seizures.
Suicide is several times commoner than in the general population, often quoted as about fivefold, though modern pooled estimates put it at two to threefold.
Prescribing
Drug | Effect on seizures | Use |
|---|---|---|
SSRIs: sertraline, citalopram, escitalopram | Barely affect threshold at therapeutic doses; few interactions with antiepileptics | First-line antidepressants |
Moclobemide | Low seizure liability | Possible antidepressant |
Tricyclics, tetracyclics, bupropion | Lower threshold | Avoided |
Clozapine | Most epileptogenic antipsychotic; dose-related | Usable in stable epilepsy with care |
Perampanel, an AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist, has the strongest link of any antiepileptic with treatment-emergent aggression, hostility and irritability.
Seizure features
Automatisms are simple, purposeless, repetitive oral and manual movements during impaired awareness, common in temporal lobe seizures and followed by amnesia.
An aura is remembered, whereas automatisms are not.
A complex partial seizure runs from an epigastric aura with déjà vu to unresponsive staring, automatisms, then post-ictal confusion and amnesia.
Violence during such a seizure is usually unplanned resistance to restraint.
A normal interictal EEG (electroencephalogram) does not exclude epilepsy.
Catamenial epilepsy is a cyclical rise in confirmed epileptic seizures tied to a phase of the menstrual cycle.
Psychogenic non-epileptic seizures
Video-EEG capture of a typical attack is the definitive investigation.
Prolactin, interictal EEG, psychiatric comorbidity and a prior epilepsy diagnosis cannot establish or exclude psychogenic seizures.
Serum prolactin rises briefly after a convulsive epileptic seizure, peaking at about 15 to 20 minutes and settling within about an hour.
The prolactin sample is drawn 10 to 20 minutes after the event and compared with a baseline.
Parkinson's disease
Physical signs are bradykinesia, rigidity, rest tremor, hypomimia and micrographia.
Depression and dementia
Depression is the most frequent neuropsychiatric complication, at about 40 to 50%, above impulse control disorders at about 13 to 29%.
An SSRI is the usual first choice because it adds little anticholinergic or hypotensive burden; nortriptyline would worsen constipation, postural symptoms and slowed thinking.
Outcome | Risk factors |
|---|---|
Depression | Female sex, young onset, akinetic-rigid form, rapid progression, marked disability, past depression |
Dementia | Older age, onset after 70, little education, postural instability and gait phenotype with axial signs such as freezing and falls |
A slow, benign course is not a risk factor for depression.
Cognitive impairment and dementia worsen prognosis, with more disability, higher mortality, greater carer burden and more care home placement.
Psychosis
Psychosis typically means well-formed visual hallucinations precipitated by escalating dopaminergic treatment, with dopamine agonists and amantadine more to blame than levodopa.
Long illness, older age, poor vision and disturbed sleep add to the risk of psychosis.
The first step is to reduce the most likely causative drug, a dopamine agonist or anticholinergic, before adding an antipsychotic or a cholinesterase inhibitor.
Quetiapine and clozapine are the only recommended antipsychotics, because their loose, fast-dissociating dopamine D2 binding spares motor function; others worsen parkinsonism.
Mania and impulse control disorders
Levodopa can induce hypomania.
Past bipolar disorder is the main risk factor for hypomania when a dopamine agonist such as pramipexole is added, and first-onset mania is rare.
Impulse control disorders (gambling, shopping, binge eating, hypersexuality) are caused by dopamine agonists acting at D2 and D3 receptors in reward circuits.
Huntington disease
Huntington disease is autosomal dominant, caused by an expanded CAG (cytosine-adenine-guanine) repeat in the HTT gene at 4p16.3, on the short arm of chromosome 4.
Presentation combines chorea, motor impersistence, years of irritability and low mood, and a parent who declined in midlife.
Psychiatric change often precedes the movements by years.
Apathy is the most prevalent behavioural change.
Cognition fails in a subcortical pattern of slowing, apathy, retrieval-type memory loss and executive difficulty.
Completed suicide occurs at about four times the general population rate and reaches about one in ten of those affected.
Imaging shows striatal atrophy, above all of the caudate head, which flattens the walls of the frontal horns.
Genetic testing for the HTT CAG expansion confirms or excludes the diagnosis and is needed above all when there is no family history; imaging, CSF (cerebrospinal fluid) and neurophysiology are only supportive.
Neighbouring movement disorders
Disorder | Clinical picture | Tests and pointers |
|---|---|---|
Progressive supranuclear palsy | Early backward falls, vertical gaze palsy with loss of downgaze, staring face, neck and trunk stiffness, apathy | Poor levodopa response |
Chorea-acanthocytosis (neuroacanthocytosis) | Feeding dystonia, lip biting, vocal tics, chorea, seizures, absent ankle jerks, early obsessional symptoms | Raised creatine kinase; acanthocytes on a fresh blood film |
Wilson's disease | Copper in the basal ganglia: disinhibition, emotional lability, dysarthria, drooling, worsening handwriting, wing-beating tremor, earlier liver disease | Kayser-Fleischer rings; low caeruloplasmin |
In Wilson's disease copper fails to bind caeruloplasmin, so caeruloplasmin and usually total blood copper are low while urinary copper excretion is raised.
Basal ganglia calcification
Calcification is dense on CT (computed tomography) and often low signal on T2 MRI (magnetic resonance imaging), in a symmetrical pallidal, striatal and dentate distribution.
Condition | Cause | Features |
|---|---|---|
Fahr disease (primary familial brain calcification) | Idiopathic, dominantly inherited; normal metabolic screen | Psychiatric, cognitive and movement presentations |
Fahr's syndrome | Identifiable cause, classically hypoparathyroidism after thyroid surgery | Hypocalcaemia and Trousseau's sign |
Multiple sclerosis
The disease
Multiple sclerosis is an autoimmune demyelinating disease of the central nervous system, with plaques favouring the optic nerves, periventricular white matter, brainstem, cerebellum and spinal cord.
It is neurodegenerative as well as inflammatory, with axonal loss and brain atrophy.
Signs vary with plaque site, and the course is mostly relapsing-remitting.
Prevalence rises away from the equator, and women outnumber men by about three to one.
Cognitive impairment is early and circumscribed, slowing processing and working memory; frank subcortical dementia comes late, after physical disability is established.
Pseudobulbar affect occurs in about one in ten people with multiple sclerosis.
Depression and suicide
Depression is the commonest psychiatric disorder, with a lifetime prevalence of about 25 to 50%, approaching 50%.
Suicidal thoughts are the most dependable evidence of depression, because the neurological disease itself produces somatic and cognitive symptoms.
Suicide risk factors include substance misuse and living alone; female sex and late onset are not risk factors.
An SSRI such as fluoxetine is first line, avoiding the anticholinergic, sedative and overdose problems of tricyclics and sedating antidepressants.
ECT (electroconvulsive therapy) is not absolutely contraindicated and can be considered with neurological liaison for severe or life-threatening depression, despite a possible risk of neurological worsening.
Mania and drug-induced mood change
Drug | Psychiatric effect |
|---|---|
Corticosteroids | Dose-related depressive symptoms; high doses cause mania after starting or raising the dose |
Antispasticity drugs | Mania, less strongly than steroids |
Interferon-beta | Carries a depression and suicidal ideation warning, though the older link has not held up in controlled data |
Natalizumab | Does not cause mania |
Starting interferon-beta in someone with past depression warrants screening and a prophylactic antidepressant.
Mania and bipolar disorder are more prevalent, with disease and drug causes and problems tolerating lithium.
No MRI plaque site has been linked to manic symptoms.
HIV and other central nervous system infections
Direct effects of HIV
Primary effects of HIV (human immunodeficiency virus) on nervous tissue are aseptic meningitis, HIV-associated neurocognitive disorder and vacuolar myelopathy.
Opportunistic infections, Epstein-Barr virus-driven lymphoma and drug effects are indirect.
Depression is among the commonest psychiatric problems and undermines antiretroviral adherence.
An SSRI with few interactions (citalopram, escitalopram or sertraline) is first choice, because ritonavir inhibits several cytochrome P450 enzymes.
HIV-associated neurocognitive disorder and dementia is a subcortical frontostriatal picture evolving over weeks to months.
It brings psychomotor slowing, early motor slowing, poor co-ordination, apathy and withdrawal, while language is largely spared and aphasia, agnosia and apraxia are unusual.
Antiretroviral therapy, suppressing viral replication in the brain, is the only treatment with good evidence; adjuvant neuroprotective agents have failed in trials.
Vacuolar myelopathy is a spinal cord disorder with spastic paraparesis, dorsal column loss and sphincter and erectile dysfunction, sparing cognition; gait disturbance is shared with HIV dementia.
Opportunistic infections
Infection | Clinical picture | Imaging and tests |
|---|---|---|
Progressive multifocal leukoencephalopathy (JC virus; AIDS-defining) | Subacute focal deficits without fever | Asymmetric non-enhancing white matter lesions reaching the U-fibres, no mass effect; CSF JC virus PCR (polymerase chain reaction) |
Cerebral toxoplasmosis | CD4 count below 100; fever | Multiple ring-enhancing lesions with oedema in the basal ganglia and grey-white junction |
Cryptococcal meningitis | Subacute headache and fever; meningism often slight | Very high opening pressure, normal CT; India ink or CSF cryptococcal antigen |
Cytomegalovirus ventriculoencephalitis | CD4 count below 50; retinitis with white necrosis and haemorrhage along vessels; subacute confusion | Ventricular lining enhancement; CSF cytomegalovirus PCR |
In progressive multifocal leukoencephalopathy, restoring immunity with antiretrovirals is the only effective approach.
Other infections
Infection | Organism | Clinical picture |
|---|---|---|
General paresis (parenchymal neurosyphilis) | Treponema pallidum | Decades after untreated infection: grandiose ideas, dementia, dysarthria, lip and tongue tremor, Argyll Robertson pupils |
Early neuroborreliosis | Borrelia burgdorferi, after tick exposure | Erythema migrans, then night-time radicular pain and facial palsy, with low mood, fatigue and poor concentration |
Herpes simplex encephalitis
Herpes simplex virus type 1 causes most adult encephalitis, while type 2 causes neonatal disease and recurrent meningitis.
The virus has a predilection for the medial temporal lobes and insula.
Acute presentation brings fever, headache, confusion, olfactory hallucinations from uncal involvement, personality change, seizures and dense anterograde amnesia.
CSF is inflammatory: lymphocytic pleocytosis, raised protein, a normal glucose ratio and red cells from haemorrhagic necrosis.
MRI is the sensitive scan, showing temporal (often unilateral medial temporal high signal), insular and orbitofrontal change.
CT is often normal early and cannot make the diagnosis unlikely; CSF PCR, cell count and EEG also carry diagnostic value.
Aciclovir should start intravenously before PCR confirms the diagnosis, because untreated encephalitis kills about 70%, far more than treated disease.
Amnesic syndrome is the characteristic sequel, because the virus destroys the hippocampus and amygdala.
Klüver-Bucy syndrome follows bilateral medial temporal damage and brings hyperphagia, hyperorality and sexually disinhibited behaviour.
Traumatic brain injury
Incidence is bimodal, raised in adolescents and young adults and in frail older people.
Depression is the commonest psychiatric sequel and is substantially raised; one selected cohort of 559 found it in 53% in the first year.
Depression after injury is associated with left prefrontal damage, chiefly dorsolateral and ventromedial, whereas right orbitofrontal lesions belong to secondary mania.
The psychosis link rests on weak designs; post-traumatic psychosis is rare, emerging one to five years after injury with persecutory delusions, voices and few negative symptoms.
Irritability and aggression are disproportionate to frustration and sometimes followed by remorse; evidence for drugs, including small propranolol trials, is limited.
Poor long-term outcome is predicted by low conscious level, long post-traumatic amnesia, older age and lower pre-injury cognitive reserve.
Severe or repeated injury raises the long-term risk of Alzheimer-type neurodegeneration.
Late post-traumatic epilepsy develops in about 30% of open head injuries against about 5% of closed ones.
Post-concussion syndrome
Post-concussion syndrome is a subjective cluster after mild head injury, with normal examination, CT and MRI, that resolves within months.
Symptoms are headache, dizziness, fatigue, irritability, poor concentration, anxiety, light and noise intolerance, visual blurring and reduced alcohol tolerance, but no psychotic phenomena.
Cognitively it slows information processing and reduces complex attention, while other domains are largely spared.
Post-concussion syndrome is told from PTSD (post-traumatic stress disorder) by the absence of re-experiencing, avoidance and hyperarousal.
Memory, perception and movement signs
Amnestic syndrome spares immediate memory (registration, digit span) but impairs anterograde learning, delayed recall, recent memory and retrograde memory.
Transient global amnesia is time-limited by definition, with each attack resolving within 24 hours.
Associative visual agnosia leaves perception and copying intact but cuts the percept off from meaning, so recognition, naming and use from sight fail.
In apperceptive agnosia, copying fails as well.
Sign | Features | Cause |
|---|---|---|
Intention tremor | Builds in amplitude during a goal-directed movement, peaking near the target | Cerebellar disease |
Staccato (scanning) speech | Separate, equally stressed syllables with irregular pauses and loudness | Ataxic dysarthria of cerebellar disease |
Meige syndrome | Bilateral blepharospasm with oromandibular dystonia | Segmental cranial dystonia |
Cataplexy | Brief emotion-triggered loss of muscle tone with awareness preserved | Narcolepsy type 1, from loss of hypothalamic orexin neurones |
Acute dystonia | Sustained painful posture such as oculogyric crisis within hours of the drug; relieved by an anticholinergic such as procyclidine | Dopamine D2 antagonists (antipsychotics, metoclopramide) |
Stimulus-sensitive myoclonus | Shock-like jerks set off by noise or touch, with dementia progressing over months, ataxia and mutism | Sporadic Creutzfeldt-Jakob disease |
Rehabilitation and follow-up
Stroke rehabilitation under NICE (National Institute for Health and Care Excellence) guidance means at least three hours daily on five days a week, or therapy on at least five days for those who cannot manage that.
Behaviour is managed with predictable routines, rest, prompts and memory aids, and by analysing its antecedents and consequences.
Drugs are started cautiously, weighing sedation, falls, seizures and effects on recovery; antipsychotics need particular caution in dementia with Lewy bodies.
Recovery is fastest in the first three to six months but can continue for one to two years; fatigue and late depression often delay return to work.
Stroke follow-up includes review at six months and then annually.
Driving stops for at least one month after stroke for a car licence, usually six months after a first unprovoked seizure, and twelve seizure-free months in established epilepsy.
A lasting power of attorney must be made while the person still has the relevant capacity.