Basal Ganglia and Difficulty Walking Flashcards
The basal ganglia include. . .
. . . the caudate, putamen, globus pallidus, and subthalamic nucleus.
Striatum
The caudate and putamen together
Lenticular nuclei
The putamen and globus pallidus
When the basal ganglia are affected by cerebrovascular disease, the ___ is often also affected
When the basal ganglia are affected by cerebrovascular disease, the surrounding internal capsule is also often affected
This causes the predominant manifestation to be contralateral weakness, with movement disorders being relatively uncommon in this scenario
Basal Ganglia: The Direct Circuit
Basal Ganglia: The Indirect Circuit
Basal Ganglia: Influence of dopamine from the substantia niagra
In Parkinson’s disease, there is breakdown of the ___, which has an ___ effect on the basal ganglia.
In Parkinson’s disease, there is breakdown of the substantia niagra, which has an inhibitiory effect on the basal ganglia.
Coronal view of basal ganglia
Saggital view of basal ganglia
Steppage gait
The foot is lifted high off the ground and is slapped down. This occurs when there is dorsiflexion weakness causing foot drop
Trendelenburg gait
The pelvis drops toward the opposite side when the weight is balanced on the leg on the affected side during walking. This occurs when there is gluteal muscle weakness.
Parkinsonian gait
stooped, small-stepped, shuffling gait, with difficulty turning
Magnetic gait
The feet are lifted only briefly off the ground before being returned briskly to the ground (as if a magnet were pulling them down).
This can be seen in normal pressure hydrocephalus
Ataxic gait
A wide-based and unsteady gait, with swaying of the body and poor balance, often with occasional adduction of the knees with stride.
This is seen in cerebellar dysfunction (as can be seen in alcohol intoxication) and severe proprioceptive dysfunction.
Spastic gait
The leg is extended, the foot plantar flexed, and the entire leg circumducted (swung out to the side) with each step. If both legs are spastic, this pattern can lead to a scissor gait.
The knees are often flexed and individuals are slightly hunched with a lower center of gravity, seeming to slightly swing feet in a circular motion with each step.
This is a pattern seen with central nervous system dysfunction of the motor system (brain, brainstem, and/or spinal cord).
Movement disorders are broadly classified as either ___ or ___
Movement disorders are broadly classified as either hyperkinetic (increased movement: tremor, chorea, myoclonus, dystonia, tics) or hypokinetic (decreased movement: bradykinesia as is seen in parkinsonism)
Parkinson’s disease (in so many words)
A neurodegenerative disease with the core features of tremor, bradykinesia, rigidity, and postural instability.
Additional motor features include decreased facial expression (hypomimia), decreased blink rate, small handwriting (micrographia), stooped posture, shuffling gait with reduced arm swing, festination (increasingly rapid small steps), difficulty turning when walking, and difficulty turning over in bed.
The constellation of some or all of these motor features is referred to as parkinsonism.
Causes of parkinsonism
- Idiopathic Parkinson’s disease
- Medications: most commonly antipsychotics and antiemetics
- Cerebrovascular disease (vascular parkinsonism)
- Toxins, including manganese and MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
- Metabolic conditions such as extrapontine myelinolysis
- Neurodegenerative diseases aside from idiopathic PD, called the Parkinson-plus syndromes
Natural history of Parkinson’s disease
- Tremor, bradykinesia, and rigidity beginning unilaterally, but usually becoming bilateral
- Some patients may have a tremor-predominant form w/o much rigidity
- Some patients have no tremor at all and have predominant bradykinesia and rigidity (akinetic-rigid form)
- Some patients may have predominant postural instability and gait dysfunction
Genetic links to Parkinson’s
Most cases are idiopathic, however:
Familial forms are associated with mutations in a growing number of genes including LRRK2 (autosomal dominant) and parkin (PARK2; autosomal recessive with onset in youth).
Tremor in Parkinson’s disease
- Most commonly hand tremor present at rest and resolving with movement
- Rest tremor may emerge when distracting the patient, for example, by asking the patient to perform serial seven subtractions.
- Typically presents unilaterally and, although it may become bilateral throughout the course of the disease, it often remains asymmetric in its severity
- Tremor of the jaw may also be present, but tremor of the head (as is seen in essential tremor) is not typically a feature of Parkinson’s disease.
Bradykinesia in Parkinson’s disease
Bradykinesia denotes slowing of movements
This may be evident in observing the patient’s normal activities, and can be elicited on examination by testing finger tapping, foot tapping, or repeated pronation–supination movements (“as if screwing in a light bulb”).
These movements should be tested one side at a time to avoid entrainment, which may mask asymmetries.
Rigidity in Parkinson’s disease
- The side(s) of the body with tremor and/or bradykinesia may be noted to have cogwheel rigidity
- This can be brought out by the technique of reinforcement, asking the patient to make circles or other repeated movements with the hand on the side opposite the limb being evaluated for rigidity.
- In idiopathic PD, rigidity is commonly asymmetric, affecting the limb(s) with tremor more so than the others.
- Axial rigidity can be evaluated for by moving the patient’s neck passively through its range of motion.
Postural instability in Parkinson’s disease
- Tends to emerge later in the course of Parkinson’s disease
- Can be assessed using the pull test to look for retropulsion
- Examiner stands behind the patient with the patient’s back to the examiner, preferably with a wall behind the examiner
- Examiner then explains that she or he will be pulling briskly on the patient’s shoulders and that the patient should maintain balance however necessary
- Normal patients will require no steps or 1-2 steps to maintain balance
- Parkinsons patients will exhibit retropulsion, requiring several (more than three) small steps to regain balance, or in severe cases, the patient will simply fall backward.
Myerson’s sign / glabellar sign
When tapping slowly and rhythmically between the eyes, normal individuals will blink several times and then stop blinking.
Patient’s with Parkinson’s disease may not extinguish the blink response and continue to blink with each tap
Nonmotor aspects of Parkinson’s disease
- Fatigue, depression, anxiety, dementia, autonomic dysfunction (including constipation, orthostatic hypotension, urinary dysfunction), decreased sense of smell, and REM sleep behavior disorder (RBD)
- In RBD, patients act out their dreams, which often involve kicking, punching, and/or running
- RBD is associated with a high risk of future development of a neurodegenerative disorder
- Some of these may precede motor symptoms of Parkinson’s
Differential for tremor-predominant Parkinson’s
Essential tremor, drug-induced tremor, physiologic tremor, and hyperthyroidism
Improvement in symptoms with ___ is suggestive of PD.
Improvement in symptoms with levodopa is suggestive of PD, although some Parkinson-plus syndromes may have an initial response to levodopa.
Treatment of Parkinson’s disease
- Pharmacologic treatment of PD is symptomatic, and therefore should begin when the disease begins to interfere with activities of daily living.
-
Levodopa the main treatment, given combined with carbidopa.
- Carbidopa inhibits peripheral dopamine breakdown, reducing peripheral side effects
- Dopamine agonists: pramipexole and ropinirole
- Catecholamine O-methyl transferase (COMT) inhibitors
- Anticholinergics: trihexyphenidyl is used predominantly for tremor
- Monoamine oxidase B (MAO-B) inhibitors: selegiline and rasagiline
- Amantadine: particularly useful in the treatment of dopamine replacement–induced dyskinesias
Non-pharmacologic treatment for Parkinson’s
In addition, exercise (aerobic and tai chi), speech therapy (for hypophonia if present), and psychiatric care (if depression, anxiety, or psychosis is present) are all important aspects of supportive care for PD.
Up-side and Down-side to Levodopa
Levodopa is more effective than dopamine agonists and causes fewer initial side effects, but may be associated with a higher risk of subsequent motor complications (dyskinesias) than dopamine agonists.
Side effects of dopamine agonists
Side effects of dopamine agonists include daytime somnolence, peripheral edema, psychosis, hallucinations, and impulse control disorders (including hypersexuality, pathologic gambling).
Side effects of levodopa
Dizziness and nausea, which may be ameliorated by taking the medication with food (although this can decrease the absorption of the medication if the medication is taken with a high-protein meal).
What medication to start a patient on when they first present with Parkinson’s
Some practitioners suggest that younger patients should initially be treated with dopamine agonists, whereas patients who develop the disease later in life should begin immediately on levodopa.
Younger patients will likely survive longer with the disease and be prone to later treatment-related motor complications with levodopa.
Wearing-off of levodopa
As Parkinson’s disease progresses, Levodopa becomes less effective.
COMT inhibitors potentiate the effects of carbidopa-levodopa and can be added to this medication late in disease course.
In patients with tremor predominant Parkinson’s, what is the medication of choice?
Anticholinergic medications such as trihexyphenidyl
However, due to anticholinergic side effects such as confusion, this medication is often avoided in older adults.
Parkinson’s therapy algorithm
Treatment-induced dyskinesias in Parkinson’s disease
-
Degeneration of the dopaminergic pathway leads to hypersensitivity to dopamine replacement, which can cause dyskinesias (usually involuntary choreoathetoid movements)
- Dyskinesias usually arise after about 5 years of levodopa therapy
- Dyskinesias can be treated with addition of amantadine or with lowering of levodopa dose
- Many long-time Parkinsons patients are caught between a rock and a hard place: being parkinsonian or being dyskinetic from levodopa use
Deep brain stimulation in the treatment of Parkinson’s disease
- Surgical implantation of stimulating leads in the subthalamic nucleus (STN) or globus pallidus interna (GPi) connected to a stimulator that is placed in the soft tissue of the chest
- DBS increases the amount of time the patient spends in the “on” state without dyskinesias
- Patients will not improve beyond their best response to levodopa and will still require medications
-
DBS only ameliorates motor symptoms, and generally does not lead to improvement in non-motor aspects of Parkinson’s
- Patients with cognitive impairment or psychiatric disease are generally not considered candidates
- DBS can also be considered in essential tremor and dystonia, although it is not currently used in Parkinson-plus disorders.
Surgical complications of DBS
Intracerebral hemorrhage and intracranial infection
Both very serious risks, but they are quite rare
Drug-Induced Parkinsonism
Most commonly induced by:
- Antipsychotics: more common with first-generation antipsychotics, but can occur with second-generation antipsychotics
- Dopamine antagonist antiemetics: metoclopramide, prochlorperazine
- The rarely used antihypertensives reserpine and alpha-methlydopa
- Rarely with valproic acid, although valproic acid more commonly induces essential tremor
Treatment is ideally discontinuation of the offending medication when possible (will then reverse in ~months). If ongoing antipsychotic treatment is necessary for the underlying disorder, clozapine can be considered (although this requires monitoring of CBC due to risk of developing agranulocytosis with this medication).
“Unmasking” of PD in patients on antipsychotics
An important diagnostic consideration in older patients who develop parkinsonian symptoms while on antipsychotic medications or dopamine-blocking antiemetics is whether idiopathic PD is emerging or being in some way “unmasked” by antidopaminergic therapy
In such patients— especially if there is no improvement with removal of the offending agent—dopamine transporter imaging can be useful since this will be normal in drug-induced parkinsonism but abnormal in PD (or any Parkinson-plus syndrome).
Tremor
An involuntary, rhythmic oscillation of a body part
Chorea
Involuntary, irregular, purposeless movements that flow and occur in a random fashion
Dystonia
Sustained muscle contraction, often with a twisting or squeezing component
Myoclonus
A sudden, brief, shock-like movement
Ticks
Brief “stereotypic” movements or vocalizations associated with an urge to move
Coprolalia
When a vocal tick involves obscene language
Tourette’s syndrome
- Involves motor and vocal ticks that persist > 1 year
- Appears before the age of 18
- Generally improves in early adulthood, even w/o treatment
- More common in boys
- Patients may transiently suppress ticks, but it is associated with an urge to have the tick, and releasing is associated with relief
- Often comorbid with OCD or ADHD
- Treatments: Clonidine (central alpha agonist), clonazepam (a benzodiazepene), haloperidol (dopamine agonist)
Essential tremor
- Most common movement disorder in adults
- Often postural, and does not occur at rest
- Common complaint is difficulty holding eating utensiles or dropping beverages
- “High frequency” tremor
- May involve hands, arms, head, and even voice
- Improves with alcohol, and many patients try to self medicate
- Worsens with anxiety
- Often familial, autosomal dominant
- Treatments: Propranolol (beta blocker), primidone (GABA agonist)
Parkinson’s summary image
Contraindications of levodopa
- Antipsychotics (Since antipsychotics block dopamine receptors)
- MAOi’s (produce hypertensive crisis)
Bromocriptine
Dopamine agonist sometimes added in conjunction with levodopa. Enhances therapeutic efficacy of levodopa without increasing risk of dyskinesias. Also used to treat hyperprolactinemia.
Contraindicated in patients with psychosis as it tends to worsen symptoms. Also contraindicated in patients with history of MI or PAD, as it may cause vasospasm.
Amantadine
Antiviral for influenza that was accidentally discovered to have antiparkinsonian action.
Enhances dopaminergic signaling in the brain by an unknown mechanism. Less efficacious than levodopa, but fewer side effects. Particularly useful in patients developing tolerance to levodopa and patients with bradykinesia/rigidity domintant disease.
MAOA vs MAOB
MAOA metabolizes norepinephrine and serotonin and is the therapeutic target of MAOi’s used to treat depression.
MAOB metabolizes dopamine and is the therapeutic target of MAOi’s used to treat Parkinson’s disease.
Trihexyphenidyl
Most common antimuscarinic used to treat Parkinson’s. Especially common for use in tremor-predominant disease.
Type of movements produced by spinal cord lesions vs basal ganglia lesions
Lesions to the spinal cord that produce movements will produce simple, tremor-like movements.
Lesions to the basal ganglia that produce movements will produce complicated and more fluid movements.
Unilateral, acute onset chorea is usually caused by a lesion in the. . .
. . . sub-thalamic nucleus
Huntington’s
- Onset ~40 years of age
- Autosomal domintant inheritance, increasing in severity over generation due to increase in tandem repeat length
- Atrophy of the caudate
- Bilateral chorea
- Sometimes with mood change/personality change, dementia
Movement disorder caused by chronic/high dose antipsychotic therapy
Tardive dyskinesia
Chorea is sometimes described as appearing quasi-____.
Chorea is sometimes described as appearing quasi-purposeful.
Hemiballismus
A type of chorea caused in most cases by a decrease in activity of the subthalamic nucleus of the basal ganglia, resulting in the appearance of flailing, ballistic, undesired movements of the limbs.
The tardive dyskinesia-type effects that can arise from antipsychotic treatment are NOT associated with ___.
The tardive dyskinesia-type effects that can arise from antipsychotic treatment are NOT associated with changes to the activity of the substantia nigra.
The effects on the substantia nigra’s signaling create the parkinsonian symptoms, but the tardive dyskinesia comes from a different etiology
Difficulty walking exam findings chart
Basal ganglia signaling in different pathologies
