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1

Definition of delirium

Disturbance of consciousness (reduced clarity of awareness of environment) with reduced ability to focus, sustain or shift attention

Change in cognition (#1 is disorientation, also memory, language) or the development of a perceptual disturbance not better accounted for by dementia

Disturbance develops over short period of time (usually hrs to days) and tends to fluctuate over course of the day

2

Causes of delirium

Non-structural
1) Infectious - meningeal infections (bacterial/fungal), encephalitis (viral), cerebral abscess (bacterial/fungal)

2) Toxic** - Sedative hypnotics drugs (benzos, barbs, alcohol), pain meds (opiates), psychotropics (PCP, TCA overdose, other drugs (penicillins, cephalosporins, salicylates, carbon monoxide, anticonvulsants, clonidine, cefepime, anticholinergics), drug withdrawal (alcohol)

3) Metabolic** - Systemic hypoxia, hypoperfusion, hypoglycemia*, hyperglycemia*, hyponatremia*, hypernatremia, hypercalcemia*, thiamine def, hyperthyroid, hepatic disease*, renal failure*, hypercarbia from pulm failure, hyperthermia, sepsis, systemic infection, TTP

If lytes are normal, consider ABG for lung issues.

UTI is common - mechanism may be secondary to inflammatory milieu (cytokines...)

4) Epileptic

Structural
1) Vascular - acute IPH, acute SAH
2) Traumatic - acute epidural hematoma, subdural hematoma, diffuse axonal injury, concussion
3) Neoplastic - mass lesion, leptomeningeal mets

Non-neuro etiology is most common (toxic, metab, infx)
Neuro etiology rarer (epileptic*, parietal lesion, multifocal emboli, CNS infx)

Note: remember we can have non-convulsive status

In ALL patients, think drugs. Young is illicit. Old is Rx.

3

Workup of delirium

Acute delirium should be approached as a medical urgency as many of the etiologies can lead to rapid demise

Standard workup should have:
1) CBC
2) Na, Ca
3) Serum gluc
4) Renal and hepatic tests
5) UA
6) Blood Cx
7) UTox

The following should be considered depending on the circumstance:
1) ABG
2) CXR
3) HCT
4) LP
5) EEG

4

Management of delirium

1) treat underlying cause

2) Avoid any benzos for agitation

3) Freq re-orientation

4) Window bed

5) Allow family to stay overnight

6) Low dose atypical neuroleptics if needed

7) Avoid physical restraint in almost all cases

8) Give thiamine

5

Delirium prognosis

Delirium in hospitalized elderly has poor prognosis

50% will require discharge to institutions

Many will die within a year

Delirium therefore is a symptom of a serious underlying process

Dementia is a risk factor for delirium

6

Dementia definition

Development of multiple cognitive deficits manifested by both
1) memory impairment (can't learn new information or recall previously learned info)
2) One or more of the following disturbances: Aphasia, apraxia, agnosia (failure to recognize despite intact sensory function), disturbance in executive function (planning, organizing, sequencing, abstracting)

Cognitive deficits each cause significant impairment in social or occupational functioning. Significant decline from previous level of functioning

For AD - gradual onset and continuing decline

7

What is the number 1 cause of dementia?

AD

8

5 cognitive domains

DSM V requires 2 or more to be dementia. DSM 4 required 1 plus memory

1) Memory - temporal
2) Language - frontal (broca's), temporal (Wernicke)
3) Praxis - parietal - trouble getting dressed, using a device
4) Nosis - Parietal/occipital - ability to recognize surroundings and make sense of them - getting lost
5) Executive function - frontal - managing own finances, making a recipe, usually a later feature

9

Prosopagnosia

inability to recognize faces

10

Subacute vs chronic dementia

Subacute - typically caused by metabolic, structural, or infectious process. CJD, B12, Chronic SDH, Mass lesion, endocrinopathy

Chronic - typically neurodegenerative or vascular. AD, Huntington Disease

11

Cortical vs subcortical dementia

Cortical - involve cortical functions. AD, vascular dementia, FTD

Subcortical - involve subcortical white matter and are typified by overall slowness of thought and decreased motivation. HIV dementia, Parkinson dementia, Huntington dementia

12

Causes of dementia

1) Neurodegenerative - AD, DLB, Pick Disease, FTD, HD, PD

2) Vascular - multiinfarct, hypoperfusion, CADASIL, Binswanger's disease

3) Infectious - HIV (R), general paresis, PML (R), SSPE, CJD

4) Structural - hydrocephalus (R), subdural hematoma (R), mass lesion (R), radiation encephalopathy

5) Toxic/metabolic - hypothyroid (R), B12 (R), Korsakoff, Wilson (R), Chronic drug intox (R)

6) Paraneoplastic (R)

7) MS

8) pseudodementia (R)

(R) is reversible

13

Recs for dementia workup

Depression screen

MRI

TSH/B12

14

NPH

Triad of Gait disorder, incontinence, dementia (usually in that order)

Caused by pressure on the frontal subcortical fibers by large ventricles

Can be primary or secondary

Diagnosis should be confirmed by objective improvement in gait after removal of CSF by LP or lumbar drain

15

Alzheimer Disease

Most common form of dementia

Very much disease of memory system first

Risk factors = age, though not confined to the elderly, low education level, Genetic mutation in B-APP, PS-1, PS-2, Down Syndrome

Felt to be caused by accumulation of abnormal B-amyloid plaque

Clinical features:
1) Gradual loss of short term memory
2) Intellectual decline
3) Loss of visuospatial orientation
4) Gradual loss of eloquent speech with relative preservation of superficial speech until late
5) Paranoid delusions and agitation
6) Late loss of motor functions and continence
7) Seizures in 10% of patients

16

Dx and Tx of AD

Clinical dx. Exclusion of other causes if suspected - routine B12, TFTs, neuroimaging. If indicated RPR, LP, PET, more

Tx:
1) AChE inhibitors provide brief stabilization of decline and delay nursing home placement by less than 1 year - donepezil, rivastigmine, galantamine, tacrine

2) Memantine (NMDA antag) recently approved for moderate to severe. May reduce rate of decline.

3) Supportive management - antipsychotics, antidepressants, anxiolytics

4) caregiver support vital

17

FTD

Typically involves personality and motivation first

Memory involved later in disease

Large number of diseases within this category

Commonly misdiagnosed

18

Dementias associated with movement disorders

1) HD - triad of dementia, chorea, and FHx. autosomal dominant, caused by CAG repeat in Huntingtin protein on chromosome 4

2) DLB - dementia with parkinsonian features

3) Wilson - never forget to consider it in younger person with dementia, behavioral changes, movement disorder or liver failure. Caused by Cu accumulation in brain due to mutation in ABC transporter gene on chromosome 13. Auto recessive

4) PD - dementia is LATER feature and is subcortical. Seen in 10-20% of PD patients.

19

Lewy Body Disease

Thought to be underdiagnosed

Should not be confused with PD. The dementia should occur within 2 years of the onset of parkinsonism.

More fluctuation than in AD

More psychosis than AD

Exquisite sensitivity to neuroleptics

Extrapyramidal features (rigidity, no tremor)

Sleep disturbances

Hallucinations common - visual

May have a response to AChE inhibitors

20

Vascular dementia

Can either be caused by multiple small strokes or a few strokes in eloquent locations

Typically more abrupt in onset than AD with stepwise deterioration and focal neuro signs

Treatment is by control of risk factors to prevent further progression

21

CJD

Prion disease

Multiple causes - sporadic form is 1 in 1 million. Inherited form caused by PrP mutation. Iatrogenic form from dural and corneal grafts. Also a transmissable form.

Rapidly progressive dementia syndrome with myoclonus

Typical EEG pattern (periodic sharp wave complexes)

No treatment is effective for the dementia

Typically causes death within 6 months to 1 year.

22

Pseudodementia

Caused by depressive syndrome

Withdrawal form social behaviors, disruption in sleep-wake cycle, altered eating pattern

Pay attention to the types of answers given on MSE!

In pseudodementia, patients will often just say "I don't know" instead of providing near-misses like in dementia.

23

Anterior vs posterior cortical dementias

Anterior - Tends to produce problems with behavior and executive dysfunction. Patients can lose social graces early while having memory and intellectual functions relatively preserved. Ex is FTD

Posterior - Tend to lose intellectual function while preserving social graces. Ex is AD

24

CSF in AD

AB1-42 is decreased

Tau is increased

This is specific but not very sensitive

25

Imaging studies in AD

cortical atrophy especially in temporal and parietal cortices with hippocampal atrophy

Hypometabolism in temporal and parietal cortices

Ligands bound to APP (amyloid precursor protein) can be used in PET

Particular degeneration of cholinergic cells that project to cortex from basal forebrain, esp in nucleus basalis of meynert

26

Avg life expectancy in AD

7-10 years after diagnosis

27

Treatment of HIV associated dementia

HAART - zidovudine, indinavir, lamivudine

28

HIV associated dementia on imaging

MRI shows diffuse cerebral atrophy

Sometime white matter changes in thalamus and basal ganglia

29

What is the best prognostic and diagnostic parameter related to CSF in HIV dementia?

CSF viral load (via PCR)

As it goes down, the HAD improves