Basal Ganglia and Difficulty Walking

Question 1

The basal ganglia include. . .

Answer 1

. . . the caudate, putamen, globus pallidus, and subthalamic nucleus.

Question 2

Striatum

Answer 2

The caudate and putamen together

Question 3

Lenticular nuclei

Answer 3

The putamen and globus pallidus

Question 4

When the basal ganglia are affected by cerebrovascular disease, the ___ is often also affected

Answer 4

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

Question 5

Basal Ganglia: The Direct Circuit

Answer 5

Question 6

Basal Ganglia: The Indirect Circuit

Answer 6

Question 7

Basal Ganglia: Influence of dopamine from the substantia niagra

Answer 7

Question 8

In Parkinson’s disease, there is breakdown of the ___, which has an ___ effect on the basal ganglia.

Answer 8

In Parkinson’s disease, there is breakdown of the substantia niagra, which has an inhibitiory effect on the basal ganglia.

Question 9

Coronal view of basal ganglia

Answer 9

Question 10

Saggital view of basal ganglia

Answer 10

Question 11

Steppage gait

Answer 11

The foot is lifted high off the ground and is slapped down. This occurs when there is dorsiflexion weakness causing foot drop

Question 12

Trendelenburg gait

Answer 12

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.

Question 13

Parkinsonian gait

Answer 13

stooped, small-stepped, shuffling gait, with difficulty turning

Question 14

Magnetic gait

Answer 14

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

Question 15

Ataxic gait

Answer 15

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.

Question 16

Spastic gait

Answer 16

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).

Question 17

Movement disorders are broadly classified as either ___ or ___

Answer 17

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)

Question 18

Parkinson’s disease (in so many words)

Answer 18

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.

Question 19

Causes of parkinsonism

Answer 19

• 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

Question 20

Natural history of Parkinson’s disease

Answer 20

• 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

Question 21

Genetic links to Parkinson’s

Answer 21

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).

Question 22

Tremor in Parkinson’s disease

Answer 22

• 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.

Question 23

Bradykinesia in Parkinson’s disease

Answer 23

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.

Question 24

Rigidity in Parkinson’s disease

Answer 24

• 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.

Question 25

Postural instability in Parkinson’s disease

Answer 25

• 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.

Question 26

Myerson’s sign / glabellar sign

Answer 26

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

Question 27

Nonmotor aspects of Parkinson’s disease

Answer 27

• 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

Question 28

Differential for tremor-predominant Parkinson’s

Answer 28

Essential tremor, drug-induced tremor, physiologic tremor, and hyperthyroidism

Question 29

Improvement in symptoms with ___ is suggestive of PD.

Answer 29

Improvement in symptoms with levodopa is suggestive of PD, although some Parkinson-plus syndromes may have an initial response to levodopa.

Question 30

Treatment of Parkinson’s disease

Answer 30

• 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

Question 31

Non-pharmacologic treatment for Parkinson’s

Answer 31

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.

Question 32

Up-side and Down-side to Levodopa

Answer 32

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.

Question 33

Side effects of dopamine agonists

Answer 33

Side effects of dopamine agonists include daytime somnolence, peripheral edema, psychosis, hallucinations, and impulse control disorders (including hypersexuality, pathologic gambling).

Question 34

Side effects of levodopa

Answer 34

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).

Question 35

What medication to start a patient on when they first present with Parkinson’s

Answer 35

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.

Question 36

Wearing-off of levodopa

Answer 36

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.

Question 37

In patients with tremor predominant Parkinson’s, what is the medication of choice?

Answer 37

Anticholinergic medications such as trihexyphenidyl

However, due to anticholinergic side effects such as confusion, this medication is often avoided in older adults.

Question 38

Parkinson’s therapy algorithm

Answer 38

Question 39

Treatment-induced dyskinesias in Parkinson’s disease

Answer 39

• 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

Question 40

Deep brain stimulation in the treatment of Parkinson’s disease

Answer 40

• 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.

Question 41

Surgical complications of DBS

Answer 41

Intracerebral hemorrhage and intracranial infection

Both very serious risks, but they are quite rare

Question 42

Drug-Induced Parkinsonism

Answer 42

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).

Question 43

“Unmasking” of PD in patients on antipsychotics

Answer 43

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).

Question 44

Tremor

Answer 44

An involuntary, rhythmic oscillation of a body part

Question 45

Chorea

Answer 45

Involuntary, irregular, purposeless movements that flow and occur in a random fashion

Question 46

Dystonia

Answer 46

Sustained muscle contraction, often with a twisting or squeezing component

Question 47

Myoclonus

Answer 47

A sudden, brief, shock-like movement

Question 48

Ticks

Answer 48

Brief “stereotypic” movements or vocalizations associated with an urge to move

Question 49

Coprolalia

Answer 49

When a vocal tick involves obscene language

Question 50

Tourette’s syndrome

Answer 50

• 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)

Question 51

Essential tremor

Answer 51

• 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)

Question 52

Parkinson’s summary image

Answer 52

Question 53

Contraindications of levodopa

Answer 53

• Antipsychotics (Since antipsychotics block dopamine receptors)
• MAOi’s (produce hypertensive crisis)

Question 54

Bromocriptine

Answer 54

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.

Question 55

Amantadine

Answer 55

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.

Question 56

MAO_A vs MAO_B

Answer 56

MAO_A metabolizes norepinephrine and serotonin and is the therapeutic target of MAOi’s used to treat depression.

MAO_B metabolizes dopamine and is the therapeutic target of MAOi’s used to treat Parkinson’s disease.

Question 57

Trihexyphenidyl

Answer 57

Most common antimuscarinic used to treat Parkinson’s. Especially common for use in tremor-predominant disease.

Question 58

Type of movements produced by spinal cord lesions vs basal ganglia lesions

Answer 58

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.

Question 59

Unilateral, acute onset chorea is usually caused by a lesion in the. . .

Answer 59

. . . sub-thalamic nucleus

Question 60

Huntington’s

Answer 60

• 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

Question 61

Movement disorder caused by chronic/high dose antipsychotic therapy

Answer 61

Tardive dyskinesia

Question 62

Chorea is sometimes described as appearing quasi-____.

Answer 62

Chorea is sometimes described as appearing quasi-purposeful.

Question 63

Hemiballismus

Answer 63

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.

Question 64

The tardive dyskinesia-type effects that can arise from antipsychotic treatment are NOT associated with ___.

Answer 64

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

Question 65

Difficulty walking exam findings chart

Answer 65

Question 66

Basal ganglia signaling in different pathologies

Answer 66