Degenerative Disorders Flashcards
Delirium - Definition
AKA acute confusional state, toxic-metabolic encephalopathy
An acute disorder of attention characterized by an inability to maintain a coherent line of thought; reflects diffuse brain dysfunction related to a disruption of normal brain homeostasis, affecting arousal systems in the brainstem, diencephalon, and cortical regions
Delirium - etiology
Drugs - Intoxication and withdrawal Environmental toxins Metabolic disorders Infection Inflammation Structural lesions - TBI, stroke Seizure disorders
Evaluation of delirium
History
Physical exam, including neurologic exam (no MSE)
Labs - CMP, CBC, urinalysis, urine toxicology
ECG, Chest X Ray
CT/MRI of brain
LP if brain infection is suspected
EEG if non-convulsive status epilepticus is suspected
Dementia - definition
An acquired and persistent impairment in intellectual function with deficits in at least 3 areas - memory, language, visuospatial skills, emotion, personality, and complex cognition - which interferes with social and occupational activities
Reversible causes of dementia
Account for 10-20% of dementias
Drugs & Toxins Mass lesions Hypothyroidism Vitamin B12 deficiency Neurosyphilis CNS inflammatory diseases Severe depression Mild TBI
Irreversible Causes of dementia
Accounts for 80-90% of dementias
Alzheimer's Frontotemporal Dementia (FTD) Huntington's Disease Parkinson's Disease Lewy Body Dementia Creutzfeldt-Jakob Disease Multiple Sclerosis HIV-associated dementia Severe TBI
Evaluation of dementia
History
Physical, including neurologic exam and MSE
Labs - CMP, CBC, TSH, B12, RPR (syphilis)
Imaging - MRI or CT of brain
Cortical Dementia - 2 examples
Alzheimer's Disease Frontotemporal Dementia (FTD)
Alzheimer’s Disease - Clinical features
Most common cause of dementia in older people (50-70% of cases); survival after onset is 6-12 years
Stages of Alzheimer’s Disease
Stage I (1-2 years): Notable amnesia
Stage II (2-10 years): Obvious dementia
Stage III (8-12 years): Severe mental and physical incapacity
Mild Cognitive Impairment (MCI)
A transitional stage between normal aging and AD; in a person over 65 with MCI, the conversion rate to AD is 10-15% per year
Alzheimer’s - Neuropathology
Gross - cerebral atrophy, reflecting loss of cortical neurons and synapses
Microscopic - neuritic (amyloid) plaques and neurofibrillary tangles
Genetic risk for early onset Alzheimer’s
Down syndrome (via trisomy of APP gene on chromosome 21); other mutations of APP
Mutations in Presenilin-1 on Chromosome 14
Mutations in Presenilin-2 on Chromosome 1
Genetic Risk - Late onset Alzheimer’s
Epsilon-4 allele of the apolipoprotein E (APOE) gene
Alzheimer’s - Treatment
Acetylcholinesterase inhibitors - Donepezil, Rivastigmine, Galantamine
NMDA antagonist - Memantine
Frontotemporal Dementia
A degenerative disease of the frontal and temporal lobes; patients typically present with disinhibition, apathy, and impairment of executive function with sparing of memory until late in the course of the disease
Subcortical dementias - 2 examples
Parkinson’s Disease
Huntington’s Disease
Subcortical dementias affect the deeper gray matter structures (basal ganglia, thalamus, brainstem) and so they feature some variety of movement disorder in addition to dementia
Parkinson’s Disease - Clinical characteristics
Resting tremor Bradykinesia Rigidity Postural instability 80% develop dementia
Parkinson’s Disease - Pathology
Lewy bodies in the substantia nigra
Abnormal synuclein protein
Dopamine deficiency
Huntington’s Disease - Clinical characteristics
Dementia
Chorea
Personality Changes
Neuropsychiatric features
Huntington’s Disease - Genetics & Pathology
Autosomal dominant inheritance of an abnormal CAG trinucleotide repeat in the HTT gene; genetic testing is available
Imaging shows caudate atrophy
White matter dementias - Examples
Binswanger’s Disease
Normal pressure hydrocephalus
Binswanger’s Disease - Mechanism
Long-standing hypertension leads to ischemia and lacunar infarction of cerebral white matter; dementia is slowly progressive
Normal Pressure Hydrocephalus (NPH)
Imaging shows enlarged ventricles with normal sulci, indicating hydrocephalus and neuropathology affecting the periventricular white matter
Presents with dementia, gait disorder, and urinary incontinence
Mixed Dementias - 2 examples
Multi-infarct Dementia
Creutzfeldt-Jakob Disease
Multi-infarct dementia
Caused by a series of sequential strokes which erode cognitive function in a step-wise fashion until dementia appears; infarcts may be large vessel (affecting the cerebral cortex) or small vessel lacunar infarcts (affecting the subcortical gray and white matter)
Creutzfeldt-Jakob Disease - Mechanism
Caused by a proteinaceous infectious particle (prion); 85-90% are sporadic and most of the rest are familial; infectious causes are rare but include transmission by dura mater grafts and neurosurgical instruments
CJD - Clinical features
Patients present with dementia that progresses over weeks to months, often with confusion, psychotic features, and myoclonus; death occurs within 4-12 months
Treatment of dementia
Treatment of underlying, reversible causes
Avoidance of drugs that worsen mental status (benzos, anticholinergics)
Low-dose atypical anti-psychotics (quetiapine, risperidone) for neuropsychiatric syndromes
SSRI treatment for depression
Lewy Body Dementia
Characterized by dementia, parkinsonism, visual hallucinations, and confusion
Binswanger’s Disease
Caused by long standing hypertension leading to the development of white matter ischemia
Dementia is slowly progressive
Frontotemporal Dementia - Pathology
Abnormal tau metabolism
Neurofibrillary Tangles
Ubiquitin inclusions
