Parkinsonism and Movement Disorders Flashcards
Exam 4
The hallmark of Parkinsonism is ______
Tremor at rest
Tremor with intention or movement is usually associated with what?
- Brain lesion
- Alcohol or drug toxicity
______ is rhythmic movement around a joint
tremor
______ is muscle jerks in various areas that impair movement and coordination
Chorea
______ is a type of chorea that includes violent abnormal movements
Ballismus
______ - slow, writhing/twisting
Athetosis
______ – abnormal posture
Dystonia
____ – Single repetitive movements, especially of face
Tics
Choreathetosis combines which 3 involuntary movements?
Chorea, athetosis, and dystonia
The _____ relays signals to the motor cortex to guide movement
thalamus
Which neurotransmitter does the Substantia nigra release to control the thalamus?
Dopamine
What are the 4 parts of the basal ganglia?
- Striatum
- Substantia nigra
- Globus pallidus
- Subthalamic nucleus
Movement disorders are related to _________ dysfunction
basal ganglia
What are the symptoms of Parkinsons?
TRAP
- Tremor
- Rigidity
- Akinesia
- Postural instability
- Cognitive decline
What is the pathogenesis of Parkinsons?
Dopaminergic neuron degradation
- Nigro-striatal pathway
- Decreased dopamine levels
What is the main gene associated with Parkinsons?
SNCA - α-Synuclein (neurotransmitter release)
What are the protective vs harmful environmental components of Parkinsons?
Protective – cigarette smoke, coffee, anti-inflammatories, uric acid
Harmful – lead, manganese exposure, Vit D deficiency
How does a mutation in the α-Synuclein gene predispose someone to Parkinsons?
Lewy bodies in the substantia nigra regions of the brain
- Misfolding associated with neurodegeneration
What are the 3 diseases associated with misfolding of proteins in neurons?
- Parkinsonism
- Alzheimer’s
- MSA – Multiple System Atrophy
What are the 2 occupations that increase Parkinson’s risk?
Teaching and healthcare
What are the 3 main methods of treating Parkinsons?
- Exercise – physical therapy
- Restore dopamine levels – Levodopa
- CNS Antimuscarinics – control dopaminergic release
What should be avoided in Parkinsons treatment?
- Dopamine receptor antagonists (antipsychotic agents)
- MPTP – destroys dopaminergic neurons - Impurity in some illicit drugs (synthetic opioids)
What is the difference between dopamine and L-DOPA?
Dopamine does not cross BBB, L-DOPA does
How does carbidopa increase the effectiveness of L-DOPA?
prevents COMT from breaking down L-dopa, increasing amount that can cross the BBB from 1-3% to 10%
What is the main adverse effect of L-DOPA? What is the treatment?
Hallucinations and delusions
Pimavanserin (Nuplazid) – antipsychotic
What is the MOA of Pimavanserin (Nuplazid)?
Antipsychotic - Inverse agonist at 5-HT2A – Visual cortex
What is the On-Off Phenomenon associated with the long-term use of L-DOPA?
Periods of increased mobility, followed by marked akinesia
What are the drug interactions of L-DOPA?
Vitamin B6, MAOIs
What are the contraindications of L-DOPA?
- Psychosis (enhanced dopamine signaling)
- Glaucoma
- Melanoma
What is the medicaiton that can be given as an alternative to L-DOPA? What is its MOA?
Pramipexole - Early disease treatment
Dopamine Receptor Agonists
What are the 2 types of MAO enzymes?
- MAO-A – NE, 5-HT, Dopamine
- MAO-B - Dopamine
What is the MAOI used to treat Parkinsons? Which type of MAO does it target
Selegeline - MAO-B selective
What is the MOA of Tolcapone? How does it treat Parkinson’s?
COMT Inhibitors – Increase circulating dopamine
How is Apomorphine (Apokyn) used in the management of Parkinson’s?
Dopamine agonist – “off” periods, relief of akinesia
What are the alternative treatments for Parkinson’s?
- Lesional – ablation
- Deep Brain Stimulation – electrode placement in basal ganglia
- Stem Cell Therapy - Implantation of fetal substantia nigra
Essential Tremor is associated with _____ dysfunction
B1 receptor dysfunction – beta-blockers
What is the treatment for Benign Hereditary Chorea?
tetrabenazine
What is Benign Hereditary Chorea?
Chorea in childhood, no progression, no dementia
What is Tardive Dyskinesia? What is the treatment?
- Repetitive, involuntary movements
- Antipsychotic drugs most common cause
______ is the largest group of muscle disorders in childhood
Muscular Dystrophy (MD)
How is Muscular Dystrophy (MD) characterized?
Characterized by progressive weakness and wasting of symmetric groups of skeletal muscle
What is the most severe and common MD?
Duchenne Muscular Dystrophy
What gene is absent in children with Duchenne Muscular Dystrophy?
Dystrophin
What is the treatment for Duchenne Muscular Dystrophy?
- No cure – gene therapy
- Maximize quality of life
- Corticosteroids
- Beta-2 agonists – muscle strength
- Orthopedic braces
- Physical Therapy
- Respiratory – Assisted ventilation
______ sign is the hallmark sign for Duchenne Muscular Dystrophy
Gowers - using hands to push on legs to stand
______ is a non-progressive motor disorder of the CNS resulting in alterations in movement and posture
Cerebral Palsy
What are the signs of cerebral palsy?
- Hyper- or hypo- tonia
- Scissoring of legs
- Absence of reflexes or reflexes extended beyond expected age
- Failure to meet developmental norms
- Seizures
What are the therapies for cerebral palsy?
Surgery - Tendon release and Intrathecal pump
Medication - Botox and Baclofen
What are the most common causes of CP?
- Trauma
- Hemorrhage
- Anoxia
- Infection
What is the onset and symptoms of Huntington’s disease?
- Onset – age 30-40
- Progressive loss of muscle control, Chorea, Dementia, Death – 15-20 years after onset of symptoms
What is the cause of Huntington’s disease?
- Gene produces huntingtin protein – function unknown (neural health)
- GABA reduced in basal ganglia
- Reduction in Choline acetyltransferase (ChAT)
What are the treatments for Huntington’s disease?
- Tetrabenazine - Depletes dopamine
- Dopamine Receptor Blockers - Haloperidol
- Genetic counseling, speech therapy, PT/OT
ALS is characterized by the loss of ________
motor neurons
What is the other name for ALS?
“Lou Gehrig’s disease”
What is the main treatment for ALS? What is the MOA?
Riluzole – sodium channel blocker (damaged neurons)
- extends QOL
How is Alzheimer’s diagnosed?
autopsy
What are the theories of causes of Alzheimer’s Disease?
- Genetic predilection
- Head injury
- Dysregulated lipids
- Low estrogen
What are the 2 hallmark lesions of Alzheimer’s disease?
Neurofibrillary tangles: twisted fragments of protein within nerve cells
Senile plaques: products of dying nerve cells accumulate around protein (AB42)
What are the clinical manifestations of Alzheimer’s?
- Forgetfulness, emotional upset, disorientation, confusion, lack of concentration, decline in abstraction, problem solving, and judgment
- Insidious onset
How can Alzheimer’s be prevented?
- Cardiovascular health
- NSAIDs
- Diet and Exercise
What is the treatment for Alzheimer’s?
Palliative - Tacrine and Memantine
What is the MOA of Tacrine?
CNS ACh esterase Inhibitor
What is the MOA of Memantine?
NMDAr Antagonist
What increases the likelihood of having restless leg syndrome?
Increased in pregnancy, diabetics
What are the 4 treatments of restless leg syndrome?
- Dopamine agonists
- Gabapentin
- Benzodiazepines
- Opiates (clonazepam)
________ is a sleep disorder that is characterized by a creeping discomfort in legs and the urge to move about
Restless Leg Syndrome
Draw the pathway for levodopa metabolism and targets for dopamine receptor agonists, MAO-B antagonists, and COMT inhibitors.
Explain the relationship between the basal ganglia, motor cortex, and thalamus; and describe the pathology in movement related disorders.
Thalamus - fine-tunes movements by relaying signals back to the cortex
Basal ganglia - regulates motor activity and thalamus
Substnatia nigra - controls dopamine release to either inhibit the indirect or stimulate the direct pathway
- dopamine neurons in substantia nigra degenerate in Parkinson’s
