Basal ganglia: movement disorders week 6 Flashcards
What are the characterisitics of movement disorders?
Characteristics of movement disorders are:
- Absence of motor weakness
- involuntary movements
- interrupted or poor coordination of volitional movements
- Abnormalities of posture and muscle tone
Movement disorders are a loosely defined group of disorders of which a primary characteristic is the presence of abnormal involuntary movements. Many of these disorders are the result of basal ganglia abnormalities, but in others the anatomic substrate is unknown.
What is the prototype disease of hypokinesia?
Parkinson’s disease
What is the pathology of Parkinson’s disease?
What is the neurochemistry? (What NT levels are affected?)
How is PD treated?
What is drug-induced parkinsonianism?
Pathology: in PD, there is degeneration of dopamine-producing cells in the substantia nigra with resultant loss of dopamine in the striatum
Neurochemistry: Depletion of dopamine in the nigrostriatal pathway. Secondary enhanced activity of acetylcholine and glutamate
Treatment
a. Agents that increase dopamine transmission
b. Anticholinergic agents, possibly glutamate antagonists
Drug-induce Parkinsonianism may be caused by dopaminergic receptor blocking agents, dopamine synthesis inhibitors, etc.
What is the prototype disease of hyperkinesia?
Chorea
What NT is associated with postural/essential tremor?What diseases/drugs is this type of tremor associated with?
Dysfunction of what part of the brain is intention/end point exacerbation tremor associated with?
Postural tremor/Essential tremor - usually associated with noradrenergic activity (hyperthyroidism, familial tremor, amphetamine use, lithium carbonate)
Intention/End point exacerbation tremor (typically seen with cerebellar dysfunction as in multiple sclerosis and other entities causing cerebellar damage)
What is the inheritance pattern of Huntington’s disease? What is the mutation that causes HD?
What is the pathology of HD? (what NT is affected, where in the brain)
How is HD treated?
Chorea - rapid, unpredictable, usually low amplitude jerks. Huntington’s disease is the prototypic choreic disorder.
a. Clinical picture - autosomal dominant disorder characterized by progressive chorea and dementia
b. Pathology - loss of striatal cholinergic cells (caudate degeneration), secondary over activity of dopaminergic system
c. Molecular biology: genetic repeat disorder now isolated to specific chromosome.
d. Treatment - dopaminergic blockers, possibly cholinergic agonists -no effective treatment for dementia at the present time
What is dystonia? What is the prototype disease for dystonia?
What is the clinical picture for dystonia? (How does the patient present?)
What is the pathology?
How is dystonia treated?
Dystonia - contorted posture usually with twisting movements and muscle spasms. Prototype is spasmodic torticollis
a. Clinical picture - neck twisting that is action-exacerbated. There can be superimposed tremor. Classically, forms of dystonia are helped by special postures induced by the patient (geste antagoniste)
b. Neuropathology - brains appear normal in patients with most forms of dystonia, but the putamen is posited as the level of dysfunction
c. Treatment
1. Anticholinergic drugs
2. Botulinum toxin to weaken the overactive spasms
What is myoclonus? What is the prototypic form of myoclonus?
What is the clinical picture? (How does the pt present?)
What does the prototypic form of myoclonus usually occur in conjunction with?
What is the neurochemistry of myoclonus?
How is myoclonus treated?
Myoclonus - lightning jerks. Prototypic form of myoclonus is posthypoxic myoclonus.
a. Clinical picture - abrupt, action-induced, lightning like jerks that can cause patients to fling objects or fall
b. Clinical context - cardiac arrest from myocardial infarction, status asthmaticus (acute exacerbation of asthma that is unresponsive to initial bronchodilator treatment), motor vehicle accident.
c. Neurochemistry, decreased serotonin metabolites in the cerebral spinal fluid
d. Treatment
1. 5-hydroxytryptophan (serotonin precursor)
2. Clonazepam (benzodiazepine)
What is the clinical picture of ballism? Where does ballism usually present (proximal or distal)?
What is the most common cause of ballism?
What is the neurochemistry of ballism?
How is it treated?
Ballism: Clinical picture - Marked flinging movements, usually proximal, an exaggerated form of chorea
a. Clinical context - usually cerebrovascular accident in the area of the subthalamic nucleus (PCA distribution)
b. Neurochemistry - unopposed glutamate activity and dopaminergic activity (remember that the subthalamic nucleus stimulates the SN pr and GPi which are inhibitory to the thalamus-inhibition of movment-indirect pathway)
c. Treatment: usually dopamine receptor blockers
What age group is Gilles de la Tourette Syndrome typically present in? What other disorders is it associated with?
What is the neurochemistry of Tourette syndrome?
How is it treated?
Tics: (Gilles de la Tourette Syndrome)
a. Clinical context - usually children; associated with attention deficit disorder (ADD) and obsessive-compulsive behavior
b. Neurochemistry
– increased activity of the dopamine system (mesocortical: pathway from brainstem to cortex)
– increased norepinephrine activity (possible)
c. Treatment
– dopamine blocking agents
– agents to decrease norepinephrine activity
