Disorders of the Basal Ganglia Flashcards
What makes up the basal ganglia (aka the extrapyramidal system)?
- striatum (caudate and putamen)
- globus pallidus
- substantia nigra
- subthalamic nucleus
what is the pyramidal system
corticospinal and corticobulbar tracts
Parkinson’s disease pathophys
-loss of DA neurons in substantia nigra=less direct pw inhibition and more indirect pw stimulation of medial globus pallidus
=net increased inhibitory output of GPm to VL thalamic motor nuclei=less stim to motor cortex=clinically slow or absent movements
hyperkinetic disorders of the basal ganglia
-there is a net decrease of medial globus pallidus (GPm) output=reduced inhibition of VL thalamic motor nuclei=greater stimulation of motor cortex=xs motor activity
etiologies of parkinsonism
- use of dopamine antagonist meds
- toxic exposure to manganese of CO2
- multiple ischemic infarctions of the basal ganglia
- survivors of the encephalitis lethargica epidemic
- Parkinson’s dz-progressive degenerative d/o of unknown cause
What are the primary clinical signs of PD?
- resting tremor
- rigidity
- bradykinesia
- impaired postural reflexes
resting tremor in PD
- prominent when pt sitting or reclining
- most often involves distal upper limbs asymmetrically (sometimes chin or lower limbs)
- worse with stress
- pill-rolling
rigidity in PD
- rigid arm may not naturally swing as the pt walks
- cogwheeling=ratchet or jerky feeling created by tremor when the rigid limb is moved
bradykinesia in PD
=slowness or lack of movement
- may rock several times to get off a cahir, stooped, multiple steps to tirn around
- pt may freeze feet to the floor
- manual tasks are slow and clumsy
- eyeblinking slower
- may drool
impairment of postural reflexes in PD
- balance instability while standing or walking
- least responsive to dopaminergic medication
secondary signs found in pts with PD
- masked facies
- hypophonic speech
- micrographia
- ANS involvement: severe constipation, bladder dysfunction, or orthostatic hypotension
- REM behavior sleep disorder
how is PD diagnosed
- primarily clinically
- at least 2/4 primary clinical signs should be present
pathology of PD
-loss of pigmented dopaminergic neurons in the substantia nigra, many of which have alpha-synuclein-positive-eosinophilic-cytoplasmic inclusions called LEWY bodies
what are the synucleinopathy?
- Lewy body dementia, multiple system atrophy, PD
- accumulation of alpha-synuclein appears to play a central role in the degenerative process
PD treatment
-L-dopa and Carbidopa (decarboxylase inhibitor, limits peripheral catabolism of L-dopa before it enters the brain)
Levodopa SE in older pts
hallucinations or psychosis
problem with L-dopa
-as dz progresses each dose provide less asymptomatic on time, and more off time with bradykinesia and rigidity sometimes alternating with xs movements (dyskinesia) like choreoathetosis or dystonia
besides Carbidopa what else can increase L-dopa levels?
- COMT inhibitor-Entacapone (helps with motor fluctuations)
- MAO-B inhibitor-Selegiline
what provides some control of the resting tremor
anticholinergic drugs like trihexyphenidyl
what can help reduce the longer term SE of dyskinesia?
dopamine agonists (Ropinirole, Pramipexole) when used as monotherapy
sx fix for PD?
-pallidotomy could be placed in GPm, thereby counteracting its increased inhibition of the VL thalamic motor nuclei
OR
-deep brain stimulation-insert electrode into STN inhibiting it by means of repetitive electrical stimulations
clinical presentation of Huntington’s Disease
- choreoathetosis
- dementia
- behavioral syndromes (depression, anxiety, moodiness, agitation)
tell me more about HD
-AD degenerative dz, manifests around 35-40 with early motor symptoms
what is the clinical diagnosis for HD
-blood test demonstrating multiple trinucleotide repeats in huntingtin gene on chromosome 4
path of HD
- early: preferential loss of putaminal GABA-ergic neurons
- later: cholinergic neurons are also lost
- grossly: atrophy of caudate nuclei with less severe atrophy of cerebral cortex
caudate atrophy in advanced HD
-detected on MRI or CT scans where frontal horns of the lateral ventricles appear relatively enlarged
drugs for HD
- dopamine antagonist drugs help less choreoathetosis and psych problems
- Tetrabenazine, catecholamine depleter also helps reduce the choreoathetosis
