Term
| Parkinson’s Disease history and incidence |
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Definition
- 1817 “An Essay on the Shaking Palsy”
• Originally classified as a motor disorder, now much more complex
- Progressive neurodegenerative disease
- 100–200/100,000 people >40 years of age
• Uncommon <40 years of age
• Rapid increase in incidence >60 years of age • Mean age of diagnosis: 70.5 |
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Term
| parkinson's disease pathophysiology |
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Definition
• Largely idiopathic, thought to be interplay of environmental and genetic factors
• Dopamine depletion from basal gangliaà disruptions in connections to thalamus and motor cortex
- See normal, slow decrease in dopamine through lifespan
- With PD, this dopamine cell loss is expedited |
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Term
| brain structures involved in parkinsons disease |
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Definition
• Basal ganglia:
• Substantia nigra (SN)
• Substantia nigra pars compacta (SNc)
• Striatum
• Globus pallidus (GP)
• Subthalamic nucleus (STN)
• Thalamus |
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Term
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Definition
Just associate basal ganglia, dopamine depletion, and Parkinson's disease together. We can see that when we have a decreased amount of dopamine here at this motor neuron level, then we're going to see manifestation of movement disorders.
The key takeaway with this graphic here is that we have our normal state versus our Parkinsonism state. We have excitatory, inhibitory, and modulatory neurons that are all happening that allow for movement to occur. With Parkinson's, we get some increase in the inhibitory motor neurons. And what that's going to do is result in the bradykinesias that we're going to talk about, which is this slowing of movement.
We also get an increase in some of the excitatory things. That's where we get this tremor and these other extra movements that we talk about here. |
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Term
| Lewy body formation in parkinson's disease |
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Definition
• Abnormal aggregates and inclusions of proteins (alpha-synuclein) inside nerve cells
• “protein tangles” “misfolded proteins”
• Similar protein aggregation and inclusion body formation has been found in many other neurodegenerative diseases |
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Term
| inflammation in parkinson's disease |
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Definition
| • New research showing decreased inflammatory state->decreased incidence of idiopathic PD |
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Term
| parkinson's disease risk factors |
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Definition
- Environmental exposure
• Exposure to pesticides
• High consumption of dairy
• Tobacco is protective (not an excuse to smoke!)
- Genetic
• Approximately 15–20% of people with PD have a direct family member with PD
• Mutations: SNCA, LRRK2, PARK2, PARK7, PINK1
-Risk factors vs. early manifestations?
• Depression, constipation, orthostatic hypotension |
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Term
| parkinson's disease classifications |
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Definition
- Parkinsonism: general term, group of neurological disordersàmovement disorders
• Parkinson’s Disease (PD)
• Multiple system atrophy (MSA)
• Drug-induced Parkinsonism
• Progressive Supranuclear Palsy (PSP) • Vascular Parkinsonism
• Dementia with Lewy bodies (DLB)
• Corticobasal degeneration |
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Term
| parkison's disease clinical presentation |
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Definition
- Tremor, bradykinesia, rigidity • Later: postural instability
- Tremor: presenting symptoms approximately 75% of time
• “Pill-rolling” resting tremor, initially unilateral • May “sense” tremor before observable
• Distract->increase observable tremor
- Bradykinesia
• Generalized slowness of movement
• Misdiagnosed frequently: weakness, incoordination, tiredness
• Manifestations: difficulty with manual dexterity, shuffling gait
- Rigidity:
• Increased resistance to passive movement
• “Cogwheel rigidity”
• Typically begins unilaterally, same side as tremor
- Postural instability:
• Feeling of imbalance and tendency to fall
• Usually appears later in course of disease
• So if appears early, consider other parkinsonism
• “Pull test”->Caution, be ready to catch!
• Normal postural reflexes: maintain balance, single
step backwards
• Instability: fall or multiple steps backwards |
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Term
| classic visible findings in parkinson's disease |
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Definition
| masklike face, stooped/leaned forward posture, rigidity and trembling of extremities and head, shuffling gait w short steps, reduced arm swinging |
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Term
| Parkinson's disease: More Than Motor |
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Definition
- Dementia
• Spectrum: Lewy body dementia vs. PD with dementia
- Hallucinations
• Visual most common
- Mood disorders
• Depression, anxiety, apathy
- Sleep disorders
• Reported as most troublesome nonmotor symptoms
- Autonomic dysfunction
• Orthostatic hypotension, constipation, urinary changes |
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Term
| parkinson's disease diagnosis |
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Definition
- Clinical diagnosis
• 84% diagnostic accuracy with specialists
- Bradykinesia plus either tremor or rigidity • Postural instability comes later
- Beneficial response to dopaminergic tx is supportive • Other Parkinsonisms don’t respond well
- Striatal dopamine transporter imaging (DaTscan) is supportive but not recommended
• Will not differentiate PD from other Parkinsonisms
- Gold standard for true definitive diagnosis is neuropathologic examination |
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Term
| parkinson's disease Progression and Prognosis |
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Definition
• Highly variable, extremely difficult to predict the course
• Approximately 75% poor outcome by 10 years form diagnosis (death, dementia, postural instability)
• Presence of dementia is associated with increased mortality |
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Term
| parkinson's disease Pharmacologic Management |
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Definition
- Carbidopa/levodopa
• Standard, go to for >65 years of age at diagnosis
- Dopamine agonists:
• Bromocriptine, ropinirole
• Approved as single agents, typically preferred if younger age at diagnosis or early symptoms
• Longer duration of action
• Do not compete with proteins for transport
- MAO-BInhibitors:
• Selegiline, rasagiline, safinamide
• Possible neuroprotective properties |
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Term
| parkinson's disease Nonpharmacologic Management |
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Definition
• Routine exercise
• Physical therapy
• Speech therapy
• Occupational therapy • High fiber diet
• Increased hydration
• Low fat
• Protein restriction is not usually necessary |
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Term
| parkinson's disease Surgical Management |
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Definition
- For individuals with levodopa-responsive PD->refractory to medication:
• Deep brain stimulation
• Continuous levodopa- carbidopa intestinal gel (LCIG) |
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Term
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Definition
• Involuntary, rhythmic tremor
- More apparent with deliberate action
• Unilateral onset->contralateral progression
• Hereditary (autosomal dominant)
• Typical onset >40 years of age
• Improved with alcohol consumption
• Worse with stress, fatigue, caffeine
• No long term risk or severe disability |
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Term
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Definition
• Progressive neurodegenerative disorder
• Choreiform movements, psychiatric problems, and dementia
• Inherited: autosomal dominant
• CAG trinucleotide repeat expansion in the HTT gene on chromosome 4p |
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Term
| huntington's disease Epidemiology |
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Definition
- Worldwide prevalence: 2.7/100,000
• Europe, North America, Australia: 5.7/100,000 • Asia: 0.4/100,000
- Worldwide incidence: 0.38/100,000 per year
- Onset is most often in midlife
• <10% of cases are <20 years old (juvenile HD) |
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Term
| huntington's disease Clinical Presentation |
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Definition
• Chorea, psychiatric illness, dementia
• Slow deterioration->cognition and motor
-Motor: defining features
• Chorea: rapid, involuntary, nonrepetitive or arrhythmic movement (dance-like)
• Initial unawareness of symptoms
• Progression to interfere with diaphragm, larynx, involuntary vocalizations
• Motor impersistence: inability to maintain voluntary action
Motor dysfunction is usually first symptom
- Psychiatric: defining features
• Irritability, depression
• Onset can be years before chorea
• Paranoia, delusions, hallucinations
• Increased rates of suicide (7%), suicidal ideation (approximately 20%)
• Also consider at-risk family members
No correlation with disease duration or dementia
- Cognitive impairment: defining features
• Decline in executive functioning • May be unaware of these changes
• Dementia • Typically a later finding • Subcortical->aphasia and apraxia are uncommon
• MRI: lateral ventricles show caudate atrophy ->decline in cognition
- Chronic, slowly progressive • Average survival 10–20 years |
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Term
| early huntington's disease |
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Definition
• Functional, independent ADLs
• Involuntary movements, irritability |
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Term
| middle huntington's disease |
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Definition
• Lose ability to work, drive, perform ADLs
• Difficulty with voluntary movements, falls, weight loss |
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Term
| late huntington's disease |
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Definition
• Inability to perform ALDs, no voluntary movements, dysphagia, often nonverbal
• Vary between worse chorea and worse cognition |
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Term
| huntington's disease diagnosis |
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Definition
• Presence of typical clinical features
• Family history of disease
• No apparent family history in <8%
• CAG expansion (>36 repeats) in the HTT gene on chromosome 4p
- Molecular testing confirms diagnosis • 98.8% sensitivity, 100% specificity
• +/– Neuroimaging->rule out other possible diagnoses |
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Term
| huntington's disease Testing Considerations |
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Definition
- Who should be tested?
• Individual with symptoms (of course) • Symptomatic children
• Asymptomatic but at-risk children?
Genetic counselor! |
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Term
| huntongton's disease treatments |
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Definition
- No cure, supportive care is key
- Multidisciplinary approach to symptom management
• Neurology
• Psychiatry
• Genetics
• PT, OT, ST
• Social work
• Nutrition
• Palliative care
• Genetic counselor
- Tetrabenazine (Xenazine)
• Consider antipsychotics or benzodiazepines PRN |
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Term
| huntington's disease Advanced Care Planning |
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Definition
- Advanced directive should be discussed and created:
• Goals of care
• ICU interventions
• Resuscitation status
• Gastric tubes
• Place of care vs. place of death • Legal will
• Funeral plans |
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