Neurology

Dementias and delirium

Dementia

  • Dementia is a global impairment of intellectual, cognitive and memory without disturbance 'clouding' of consciousness and generally runs a chronic progressive course
  • Important to screen for and exclude treatable causes which can make up 20% of cases and other conditions that masquerade as dementia e.g depression
  • May be insidious with forgetfulness, increasing difficulty with ADLs, language issues, behavioural problems
  • Usually more apparent to family than patient.
  • Some dementias such as CJD have a more insidious onset rapidly becoming severe over weeks and months.
  • Acetyl choline level appears to be crucial for memory
  • Cognition and behaviour appear to be regulated at both cortical and sub cortical levels.

Alzheimer's disease

Introduction

  • Commonest cause of dementia

Aetiology

  • Progressive decline of cognitive function
  • Affects 10% of those over
  • Increased in Down syndrome
  • Linkage to gene for apolipoprotein E
  • There is reduced cholinergic, noradrenergic and dopaminergic neurotransmission
  • Neurofibrillary tangles : composed of Paired helical filaments of the microtubule binding protein tau found within the cytoplasm of neurons
  • Found in cortex in AD but not specific for AD
  • Senile plaques - composed of ? Amyloid protein and found in hippocampus, basal forebrain and cortex
  • Gene for Amyloid protein precursor (APP) on Chromosome 21.
  • Very rarely occurs as an autosomal dominant
  • Presenilin 1 and 2 genes
  • Lead to increased amyloid precursor protein

Clinical

  • Difficulty learning and retaining new information (anterograde amnesia)
  • Language difficulties, Motor problems (dyspraxias)
  • Agnosia - fails to recognise people/objects.
  • Executive planning e.g
  • steps to make a cup of tea.
  • Loss of insight, Depression, Visuospatial problems.

Investigations

  • Marked atrophy of the hippocampus seen on MRI.
  • Exclude other causes
  • All patients should have a minimum of FBC, U&E, TFTs, B12, folate, Head CT and probably VDRL

Management

  • Usual referral to memory clinic (Neurology, Geriatricians or Psychogeriatricians)
  • Local policies on use of agents
  • Allows follow up and assessment of response to and side effects and duration of treatment
  • Cholinesterase inhibitors for mild to moderate dementia - Donepezil, Galantamine or Rivastigmine
  • Memantine, a glutamate receptor antagonist
  • Prognosis: Mortality 10% per year

Dementia with Lewy Bodies (DLB)

Introduction

  • Suspect if parkinsonism and progressive cognitive impairment

Aetiology

  • Lewy bodies are also found in cortex and subcortex.
  • Lewy bodies are intracytoplasmic inclusions composed of ubiquitin, parkin and alpha-synuclein.
  • Lewy body and Alzheimer pathology often seen together e.g senile plaques

Clinical

  • Dementia with Fluctuating levels of cognition , Vivid visual hallucinations Parkinsonism
  • An increased sensitivity to neuroleptics which should be avoided, REM Sleep disturbance

Investigations

  • CT - generalised atrophy
  • Exclude other causes
  • All patients should have a minimum of FBC, U&E, TFTs, B12, folate, Head CT and probably VDRL

Management

  • Difficult
  • L-Dopa or DA agonists for motor problems but response can be poor and risk of worsening Visual hallucinations
  • Cholinesterase inhibitors may help.
  • Atypical neuroleptics may be used cautiously Quetiapine
  • Clonazepam at bedtime for sleep disorder
  • Treat depression e.g. sertraline, citalopram

Vascular (Multi-infarct) Dementia

Introduction

  • Accumulation of vascular damage

Aetiology

  • Risk factors as for ischaemic stroke

Clinical

  • Classically a stepwise downward progression of dementia in someone with history of stroke or TIA and vascular risk factors.
  • Gait - Marche a petit pas "little steps"

Investigations

  • MRI or CT scan shows Strokes involving caudate (bilateral especially),
  • Medial thalamic and hippocampus and parietal strokes cause memory defects
  • White matter ischaemia and infarcts seen on CT and MRI scan

Management

  • Manage cerebrovascular risks especially BP control

Progressive supranuclear palsy

Introduction

  • Degeneration of basal ganglia and brainstem

Clinical

  • Impaired downward gazes
  • Parkinsonism, Brainstem signs.
  • Tremor less likely than PD
  • Reptilian stare, Axial rigidity
  • Falls and Postural instability, Blepharospasm

Investigations

  • Enlarged IIIrd ventricle and interpeduncular cistern

Management

  • Supportive

Huntington Chorea

Introduction

  • Hereditary cause of dementia and movement disorder

Aetiology

  • Autosomal dominant inherited movement disorder with early onset dementia seen in 1 in 10000
  • Pathology shows mainly neuronal loss in caudate and putamen and Gene for Huntingtin on Chromosome 4p.16.3
  • The more CAG Trinucleotide with each generation the earlier the Symptoms (Anticipation) due to accumulation of polyglutamine repeats

Clinical

  • Symptoms come on usually in 40s and 50s
  • Choreiform movements, Tics, Parkinsonism
  • Progressive dementia Neuropsychiatric - anxiety, personality changes, irritable, suspicious, mania, obsessive-compulsive

Investigations

  • CT/MRI atrophy of caudate nucleus
  • Diagnosis on Genetic testing.

Management

  • Sulpiride, Tetrabenazine, Clonazepam when chorea interferes with ADLs
  • Offer Genetic counselling to family members

Frontotemporal (Pick's) dementia (FTD)

Aetiology

  • Mutations in microtubule binding protein tau
  • Tau positive inclusion bodies seen in the cytoplasm
  • Right prefrontal lobe or anterior temporal involvement leads to typical syndrome
  • Left prefrontal leads to aphasia.

Clinical

  • Early loss of social inhibitions as well as memory, Asymmetrical akinetic rigid
  • Limb apraxia, Pseudobulbar palsy
    • Spastic dysarthria
    • Lability
    • Frontal lobe signs

Investigations

  • Right prefrontal and anterior temporal atrophy on MRI
  • SPECT/PET shows anterior perfusion deficits

Management

  • ? Quetiapine 25 mg od and increasing may be used

Creutzfeldt-Jakob disease

Aetiology

  • A rapidly progressive dementia
  • There are several forms all with similar end brain pathology and prion as common factor but different clinical features
  • Sporadic, Familial, Variant, Iatrogenic

Sporadic CJD - Sporadic

  • ? gene mutation or new post translational modification
  • Mean age 66 with survival of 4 months till death
  • MRI caudate and putamen high signal
  • Elevated 14-3-3 in 60-100%
  • EEG periodic sharp waves.

Familial CJD

  • familial dominant inheritance

New variant CJD - Seen in UK

  • Related to BSE
  • Mean age Aged 29 with duration till death 14 months
  • Elevated 14-3-3 in 50%
  • MRI - pulvinar signs as involves posterior thalamus
  • EEG non specific
  • seen mainly in the UK affects younger patients with a slower clinical course than sporadic CJD

Iatrogenic CJD

  • from corneal transplants, pituitary Extracts

Clinical

  • Rapidly progressive dementia
  • Myoclonus especially with startle
  • Focal neurological deficits

Investigations

  • CSF Elevated proteins 14-3-3 and tau elevated
  • MRI - characteristic abnormalities cortical ribbon , caudate, putamen
  • EEG - periodic sharp wave complexes in sCJD
  • Brain biopsy definitive spongiform change

Management

  • Supportive and Genetic follow up for family for inherited form

Primary progressive aphasia

Aetiology

  • A Dementia predominantly affecting the speech areas
  • Predominantly language affected

Clinical

  • Can mimic a Broca's type aphasia or a Wernicke type aphasia
  • Anomia and word finding difficulties predominate

Investigations

  • EEG slowing and PET scan shows decreased activity and reduced blood flow left perisylvan hemisphere and anterior temporal cortex

Management

  • Speech and language therapy

Normal pressure hydrocephalus

Aetiology

  • Seen in the elderly with classical signs
  • There is expansion of the ventricles and damage to paracentral lobule

Clinical

  • Classical triad of Incontinence, Gait ataxia and Dementia.

Investigations

  • CT/MRI shows ventricular enlargement out of keeping to the degree of sulcal widening
  • LP shows normal pressures

Management

  • Some have a clinical improvement after removal of 30 ml of CSF
  • If clinical response to CSF removal then considered for shunting aware that there are significant risks.

Cerebral arteritis

Aetiology

  • Autoimmune condition possible due to SLE or similar disorder.
  • SLE, Sarcoid, Behcet's disease

Clinical

  • Delirium type picture

Investigations

  • Evidence of a systemic Vasculitis
  • MRI abnormal
  • CSF may show elevated WCC
  • Raised ANA dsDNA

Management

  • Seek neurology review - Steroids/other immunosuppressive agents may help

AIDS associated dementia

Aetiology

  • AIDS virus tropic for neurons

Clinical

  • Insidious onset of increasing cognitive impairment in someone with HIV

Investigations

  • HIV positive, Assess CD4 count
  • CT/MRI and LP to exclude other aids related cerebral pathology

Management

  • Dealt with later on in chapter on HAART

Treatable causes of Dementia

Causes

  • Depression, Alcohol abuse, B12 deficiency, Hypothyroidism
  • Subdural haematoma, Normal pressure hydrocephalus, Folate deficiency, Neurosyphilis

Investigations

  • All patients should have a minimum of FBC, U&E, TFTs, B12, folate
  • Head CT and probably VDRL.
  • Some patients require CSF analysis and EEG and brain biopsy.
  • Autoantibodies in other causes.

Dementias by proteins

Tau related diseases

  • Alzheimer's disease
  • Frontotemporal dementia (Pick's disease - from intracellular Pick bodies)
  • Corticobasal degeneration
  • Progressive supranuclear palsy

Synucleinopathies

  • Multiple systems atrophy
  • Parkinson's disease
  • Dementia with Lewy bodies

Delirium (Acute Confusional States)

Introduction

Introduction

  • A global impairment of intellectual, cognitive and memory
  • Disturbance of consciousness and alertness
  • Delirium is important as it is associated with increased mortality and suggests reduced cognitive reserve

Causes : Infection - UTI, Chest, Biliary sepsis, Endocarditis

  • Any infection, Uncommon infections - Malaria, Dengue in traveller, Hepatitis, Weil's disease
  • Neurological - encephalitis, meningitis, stroke (especially with Seizure or focal neurology)
  • Haematological - exclude leukaemia lymphoma
  • Drugs - steroids, anti-parkinsonian medications, opiates, anticholinergics
  • Alcohol withdrawal
  • Endocrine - Hypothyroidism, Addison's disease, Hyperthyroidism
  • Cardiology - MI

Clinical

  • Patient can be in a heightened state of agitation and alertness e.g. Delirium tremens or can be apathetic and drowsy or normal
  • The history is usually brief.
  • Retake history and ask about sex, drugs and travel in sufficient detail where appropriate
  • Examine patient top to bottom and examine the drug chart and observation chart

Causes

  • Drugs - Look up every drug especially new ones in the BNF and check levels of any where it may be help
  • Specific causes not to miss
  • Cerebral malaria - If suspicious consider treating for Malaria.
  • Alcohol Withdrawal : Alcohol is a central depressant and its withdrawal leads to agitation, confusion and possibly seizures - "Delirium tremens"
  • Agitation, picking at bedclothes, short attention span, diaphoretic, paranoia

Investigations

  • Check LFTs U&E and PTT
  • Give IV or Oral Thiamine if Deficiency suspected
  • Treat with Chlordiazepoxide or Diazepam.

Management

  • Investigate for and treat any cause
  • Involve relatives for agitated patients, calm reassuring well light environment, keep sedation to a minimum
  • Haloperidol orally or im may be used for severe agitation with close supervision

Non convulsive status epilepticus

Introduction

  • A cause of delirium not to miss

Aetiology

  • Usually temporal lobe seizure activity with confusion - complex partial type seizure

Clinical

  • Confusion, comatose

Investigations

  • Abnormal EEG

Management

  • Treat with Anticonvulsants e.g. IV diazepam

Drug induced (prescribed and illicit) Delirium

Introduction

  • Drugs should always be investigated in new delirium

Causes (Only some of the many drugs that can cause delirium)

  • Codeine and opiates
  • Antiparkinsonism drugs
  • Anticholinergics
  • Cocaine
  • Ecstasy
  • Opiates
  • Look for patches of analgesics

Clinical

  • Confusion, comatase

Management

  • Always examine the drug chart
  • In opiate toxicity consider naloxone
  • Reduce drug dosage or stop
  • Avoid anticholinergics in elderly

Hashimoto's Encephalitis

Introduction

  • Rare cause of delirium

Aetiology

  • Rare, probably autoimmune, encephalitis/encephalopathy

Clinical

  • Global depression of higher function - drowsiness and sometimes coma.
  • Amnesia and seizures

Investigations

  • High titres of Thyroid autoantibodies
  • TFTs normal.
  • MRI brain, EEG, CSF findings
  • Endocrine and metabolic screens, and viral studies.

Management

  • Most patients respond to high dose steroids
  • Improvement may take weeks, even months.
  • In some patients Plasma exchange and IVIg have been used.
  • Prognosis with treatment is generally good.

Paraneoplastic limbic encephalitis (PLE)

Aetiology

  • Autoimmune associated with cancer of lung, breast and testis
  • Diagnosis aided by finding of specific autoantibodies
  • In some cases no malignancy is found

Clinical

  • Consider in delirium in patient with a known malignancy

Investigations

  • CSF may be inflammatory and MRI - may show temporal lobe changes.
  • Antineuronal antibodies e.g. Anti - Hu (small cell), Anti Ta (Testicular), Anti Ma.
  • EEG may be show temporal lobe short waves and spikes or slowing
  • CT/PETscan chest for primary, Testicular USS, Mammography

Management

  • May improve with treatment of underlying malignancy or Immunosuppression.
  • Those without evidence of malignancy may respond to Immunosuppression

Voltage-gated potassium channel antibody-associated encephalitis

Aetiology

  • Possibly under diagnosed cause of and autoimmune encephalitis

Clinical

  • Delirium

Investigations

  • Antibodies against voltage-gated potassium channels

Management

  • Responds to steroids

Dementia due to Nutritional deficiencies

Aetiology

  • Deficiencies of Thiamine seen in alcoholics and malnourished (hyperemesis with pregnancy)
  • Nicotinic acid deficiency.

Clinical

  • Thiamine deficiency leads to Wernicke's encephalopathy
  • Nicotinic acid deficiency (Dementia, Diarrhoea, Death) causes Pellagra

Investigations

  • Red cell transketolase low

Management

  • Give IV or Oral Thiamine
  • Give Nicotinic acid

Amnestic syndromes

Aetiology

  • Memory disorders are related to damage to the medial temporal lobes and brainstem connections
  • The Hippocampi, Fornices and maxillary bodies are all structures concerned with memory and any form of structural damage can cause problems.

Causes

  • There is a list of causes of so called "amnestic" syndrome ("a mental disorder characterised by impairment of memory occurring in a normal state of consciousness; the most common cause is thiamine deficiency associated with alcohol abuse" - The inability to learn or recall new information is the key feature of this disorder.)

Causes

  • Wernicke-Korsakoff syndrome (alcohol usually but not always)
  • Thiamine B1 deficiency
  • Herpes simplex encephalitis
  • Severe Head injury
  • Cerebral anoxia - may see in those who survive out of hospital arrest
  • Bilateral tumours
  • Bilateral strokes e.g. Bilateral posterior cerebral artery occlusion
  • Arsenic poisoning
  • Hypoglycaemia
  • Carbon monoxide poisoning
  • Transient global amnesia

Transient Global amnesia

Aetiology

  • Possibly vascular but aetiology very unclear
  • Benign prognosis.

Clinical

  • Seen in Middle aged and over
  • Inability to form new memories but preservation of awareness of self and social skills and no focal neurological symptoms or signs
  • "Where am I" is constant request
  • Fully conscious and alert
  • Returns to normal in A&E or within 12 hours
  • Language normal
  • Can perform complex tasks e.g. driving
  • Patient has no memory of period except as relayed back to them
  • Often misdiagnosed as TIA or even stroke or more rarely as

Investigations

  • MRI only if Temporal lobe epilepsy considered

Management

  • No treatment necessary except reassurance
  • May recur in some rare cases

Wernicke-Korsakoff psychosis

Causes

  • Thiamine (B1) deficiency - seen in alcoholics, anorexia, persisting sickness and nausea, starvation etc...
  • Tumours or lesions involving the hypothalamus, Syphilis, Carbon monoxide poisoning, Head Injury and SAH

Clinical

  • Inability to form new memories, confabulation a lack of insight and retrograde amnesia and usually presents as a follow on to Wernicke's encephalopathy
  • and is generally known as the Wernicke-Korsakoff syndrome.
  • The Korsakoff side of things is also referred to as the Korsakoff amnestic state as the main defect is in memory formation which the patient is unable to do and confabulates quite convincingly to fill the gaps with no real insight
  • Wernicke's encephalopathy is used to describe the symptom complex of ophthalmoplegia, ataxia, and an acute confusional state
  • Wernicke encephalopathy should be regarded as a medical emergency and a very low threshold should exist for early treatment with intravenous thiamine (50-100 mg) which is the treatment of choice.

Investigations

  • Low red cell transketolase but do not wait to treat.
  • Brain MRI might show specific atrophy in diencephalic structures in Korsakoff's syndrome.

Management

  • Treat on basis of clinical suspicion of thiamine deficiency