Movement Disorders

Question 1

4 features of parkinsonism

Answer 1

1) Rest tremor - usually a pill rolling type tremor when in the hands. Present only at rest
2) Bradykinesia - overall slowness of motor tasks
3) Rigidity - increased tone in muscles independent of velocity which may have a cog-wheeling or lead-pipe component
4) Postural instability - Gait disturbance leading to falls. Usually with small, shuffling steps and decreased arm-swings

Question 2

Important causes of parkinsonism

Answer 2

1) Parkinson Disease
2) Drug-induced
3) Parkinson’s Plus syndromes
4) Vascular

Question 3

Parkinson Disease

Answer 3

Begins asymmetrically with prominent tremor. Gait instability occurs later and is associated with a typical flexed posture. Dementia develops LATE in a minority

Tx = Levodopa is mainstay of treatment, but dopamine agonists, anticholinergics, selegeline and amantadine are effective as well. Always give levodopa with carbadopa

Question 4

Drug-induced parkinsonism

Answer 4

Usually caused by a neuroleptic even for a short time.

May be indistinguishable from PD. Gait instability less frequent

TX = withdrawal of offending agent if possible. Clozapine does not cause this syndrome and is an alternative

Question 5

Parkinson’s Plus syndromes

Answer 5

1) Progressive supranuclear palsy - falling all the time within 1st year of disease, vertical gaze issues
2) Multiple System Atrophy - autonomic dysfunction early in disease
3) Dementia with Lewy Bodies - cognitive impairment in 1st year with parkinsonism, visual hallucinations
4) Cortical basal degeneration - asymmetric, highly asymmetric rigidity, apraxia, alien limb phenomenon, levitating arm

Important to distinguish from PD. Consider one if you see early dementia (DLB), early falls or eye movement problems (PSP) and early autonomic instability (MSA)

Tx = infrequent and variable response to levodopa. DLB does respond to central acetylcholinesterase inhibitors like donepezil

Question 6

Vascular parkinsonism

Answer 6

Usually involves legs more than arms. Due to multiple small strokes in basal ganglia

Tx = control progression with secondary stroke ppx. Generally poor response to levodopa

Question 7

Rest tremor

Answer 7

Usually pill rolling when in hands. Present only in rest

Low freq, high amp

Classic condition is Parkinsonism

Question 8

Postural tremor

Answer 8

Present when limbs are voluntarily maintained against gravity

high freq, low amp

Classic conditions:

1) Physiologic tremor
2) Essential tremor
3) Enhanced physiologic tremor

Question 9

Kinetic tremor

Answer 9

Occurs during voluntary movement. AKA intention tremor.

cerebellar component

Classic condition: Cerebellar tremor

Question 10

Essential tremor

Answer 10

Autosomal dominant. Mixed penetrance.

Can be in head and voice.

Predominantly postural tremor. Usually starts in middle age and worsens over time. Family history is typical. Improves with alcohol

Tx: If it interferes with daily tasks, beta blockers (propranolol) and primidone (pro-drug of phenobarbital) can be effective. Eliminate caffeine.

Make sure it’s not PD

DBS if don’t respond to drugs (Thalamus is the target)

Question 11

Wilson Disease

Answer 11

Though rare, it is vital to diagnose as this devastating disease can be prevented from progressing.

Classic triad: Movement disorders (tremors, parkinsonism, chorea, dystonia), psychiatric disturbance and hepatic failure

Can present in any order. Look for Kayser-Fleischer Rings Check serum ceruloplasmin and 24hr urine copper

Tx: Limit dietary copper intake. Penicillamine, Zn, and dimercaprol have all been used with success

Question 12

Focal dystonia

Answer 12

Blepharospasm (involuntary closure of eye), torticollis (involuntary contraction of one SCM) and writer’s cramp are the common types

Tx: Focal dystonias respond well to local injection of botox into involved muscle

Question 13

Huntington’s Disease

Answer 13

Class triad is chorea, dementia, and positive family history

Tx: Symptomatic therapies exist for the chorea, but unfortunately the disease relentlessly progresses until death

Question 14

basal ganglia function

Answer 14

Planning of movement

Lesion will show too slow movement or extra movements they didn’t want

Question 15

Cerebellum function

Answer 15

Gets motor plan and also sensory feedback

If you veer off course it will adjust you

Trouble enacting the motor plan if there is a lesion

Question 16

Chorea

Answer 16

Dance like (chore-ographer)

Damage to caudate/putamen

Question 17

Ballism

Answer 17

Classically a loss of the indirect pathway - stroke in contralateral STN

Violent flailing (ballis-tic missile)

Question 18

Dystonia

Answer 18

1 = drug-induced

Fixed muscle position

Question 19

Myoclonus

Answer 19

1 = renal failure

Rapid muscle jerk

Question 20

Tics

Answer 20

Involuntary but suppressible - the motor version of a compulsion

Question 21

Akathisia

Answer 21

Inner sense of restlessness relieved by movement

Fe deficiency can present with restless leg syndrome (Basal ganglia has Fe receptors)

Question 22

Complications of PD treatment

Answer 22

Levodopa is best treatment. It is converted to dopamine in the brain and corrects the lack of dopamine that causes the disease

Levodopa leads to complications in 3-5 years though so young patients are often started on other meds. Levodopa can cause ortho hypo, hallucinations, psychosis. on-off phenomenon, wearing-off phenomenon, dyskinesias

Dopamine agonists (pramipexole) are less effective but have less motor side effects. Can cause edema though.

MAOIs (rasagaline) have mild symptomatic benefits and may slow disease progression

Anticholinergics (trihexyphenidyl) are effective at treating the tremor but are quite sedating

Amantadine can also be effective

Question 23

Tourette Syndrome

Answer 23

neurological disorder characterized by repetitive, stereotyped, involuntary movements and vocalizations called tics

Early symptoms of TS are almost always noticed first in childhood, with avg age of onset of 7-10 years.

First sx’s usually occur in the head and neck area and may progress to include muscles of the trunk and extremities. Motor tics generally precede the development of vocal tics and simple tics often precede complex tics.

Most patients experience peak tic severity before the mid-teen years with improvement for majority of patients in late teen years and early adulthood

Some patients can suppress, hide or otherwise manage their tics in an effort to minimize their impact on functioning. They often report huge buildup of tension though when suppressing their tics to the point that they feel like tic must be expressed

TS is inherited. Some forms of ADHD and OCD are genetically related to TS

Tx: Medical therapy when tics interfere with social interactions, school performance, or activities of daily living. Goal for tics is not complete elimination but rather control of tics to alleviate the social embarassment or discomfort due to the tic.

D2 blockers (neuroleptics) are the most effective meds for treating tics, but the side effect profile (EPS,TD) is a limit to first line treatment. Haldol and pimozide are approved for TS. Haldol has 80% response rate for tic suppression

Question 24

Evaluating multifocal myoclonus

Answer 24

Note: seizure is unlikely to present in all limbs with a patient who is described as only mildly confused.

Ddx is renal failure, benign nocturnal myoclonus, CJD, meds, other metabolic derangements like liver failure and certain forms of epilepsy

Order serum lytes, renal function, LFTs. In an ICU patient with multifocal myoclonus, an EEG is ordered to exclude seizures. Brain MRI is usually unimpressive. CSF should only be obtained if there are associated signs and symptoms of meningitis or encephalitis

Tx: Correct metabolic derangements associated with RF. Levetiracetam, piracetam and valproic acid can suppress myoclonic jerks but this is not needed unless it is very disturbing to family members

Question 25

Physiological tremor

Answer 25

Very low-amp, fine tremor (btw 6-12 Hz) that is barely visible to naked eye. Present in every normal person during maintaining a posture or movement. Neuro exam results of patients with physiologic tremor are usually normal

Question 26

Enhanced physio tremor

Answer 26

High-freq, low-amp visible tremor that occurs primarily when a specific posture is maintained. Drugs and toxins induce this form of tremor

Question 27

What is the most common movement disorder?

Answer 27

Essential tremor

Question 28

Essential tremor timing, tx, and diagnosis

Answer 28

Usually middle age, but can be earlier Pronounced when patient engages in voluntary movement such as drinking a glass of water, writing, threading needle Fatigue, anxiety and temp extremes make it worse usually disappears at rest or while asleep Lose doses of alcohol helps in half of patients It's a clinical diagnosis Tx: beta blockers or primidone (an anti-seizure drug) B-blocker side effects: dizziness, confusion, memory loss in older adults so they are better choice for younger patients Also avoided in asthma, diabetes, certain heart problems Primidone side effects: flu-like, drowsy Tranquilizers like xanax (alprazolam) or valium (diazepam) can help when tremors are worsened by anxiety or tension. Side effects are confusion, memory loss BoTox can help when head or voice are involved, Used for up to 3 months at a time. When used to treat hand tremors it may cause weakness DBS to thalamus if severe and if meds aren't effective

Question 29

Latency time in ET

Answer 29

Time of onset for tremor to appear while holding arms out PD: 9s ET: 1-2s

Question 30

Athetosis

Answer 30

Twisting and writhing often associated with chorea

Question 31

Huntington genetics

Answer 31

CAG triplet repeat within Huntintin gene. Auto dominant with 100% penetrance Chromosome 4 Number of repeats correlates with manifestations of disease More than 40 repeats almost always linked to clinical disease Repeats of 26-30 sometimes Less than 25 almost never Paternal transmission leads to more repeat length increasing. Anticipation seen (esp in paternal transmission)

Question 32

Opisthotonos

Answer 32

Great rigid spasm of the body with the back fully arched and the heels and head bent back

Question 33

Primary generalized dystonia

Answer 33

DYT-1 is early onset torsion dystonia caused by mutation in the torsion A gene of chromosome 9 DYT-5 is dopa-responsive dystonia DYT-1 is most common. Starts in limb. Associated with GAG deletion in exon 5 of DYT1 (TOR1A). Large phenotypic variation. Progressive, disabling disorder that usually begins in childhood and is linked to several genetic loci. Many inherited as autosomal dominant traits cause by a deletion in torsion A gene. Begins as focal action dystonia nefore the middle of the third decade with most cases beginning in childhood. 65% progress to multifocal or generalized dystonia. 10% become segmental. 25% stay focal. Most primary dystonias have normal routine imagine. In primary torsion dystonia FDG-PET has been shown to see some metabolic differences Dx: Rule out secondary dystonia first - History of trauma or exposure to drugs, infections, cerebral anoxia, etc - Dystonia at rest rather than with action at its onset - Atypical site for age of onset (leg onset in an adult, cranial onset in a child) - Early onset of speech abnormality - hemidystonia - presence of abnormalities other than dystonia on neuro exam or general med exam - Nonphysio findings suggesting a psychogenic basis - Abnormal brain imaging - Abnormal labs Remember for primary dystonia, dystonia is the ONLY symptom. Tx: High-freq stimulation of globus pallidus, pars interna through DBS Symptom treatment with levodopa, benzos, baclofen, anticholinergics (trihexyphenidyl)

Question 34

Pathologic feature of PD

Answer 34

Loss of pigment in substantia nigra Remaining neurons may show intracytoplasmic eosinophilic inclusions called Lewy Bodies Marked striatal dopamine depletion

Question 35

Autosomal dominant cerebellar ataxia clinical classification

Answer 35

Hardin system. For late onset ADCA. Also, sporadic cerebellar syndromes include idiopathic forms of obscure etiologies marked by progressive ataxia, autonomic failure, and extrapyramidal features (like MSA) ADCA I - optic nerve, cerebral cortex, peripheral nerves ADCA II - pigmentary macular dystrophy ADCA III - pure late onset cerebellar syndrome Since this time, we refer to them as spinocereballar ataxias (SCAs) and they are more characterized based on genetic loci

Question 36

ADCA genetics

Answer 36

Most are caused by expansions, most are trinucleotides (SCA 1-3, 6-10, 12, 17) SCA 8 - CTG repeated SCA 10 - ATTCT repeated SCA 4 - no trinucleotide repeat

Question 37

ADCA age of onset

Answer 37

Most are 20-30 SCA 6 40-50 SCA 8 late 30s

Question 38

ADCA clinical features

Answer 38

Most common is SCA 3 - chromosome 14 (Ataxin 3 gene) CAG repeat. SCA 1: 6% - Ataxia, dysarthria, pyramidal signs, peripheral neuropathy, hyperreflexia, cognitive impairment. Nystagmus, hypermetruc saccades, slow saccades, ophthalmoparesis. CAG chromosome 6 SCA 2: 14% - Ataxia, dysarthria, peripheral neuropathy, hyporeflexia, dementia, myoclonus. Slow saccades. Ophthalmoplegia. CAG chromosome 12. SCA 3** 21% - Ataxia, dysarthria, spasticity, parkinsonism, amyotrophy. Lid retraction, nystagmus, saccade, dysmetria, ophthalmoparesis, square wave jerks. CAG chrom 14. SCA 6: 15% - Ataxia, dysarthria, sometimes episodic ataxoa, very slow progression, lack of FHx. Nystagmus (usually downbeating), saccadic pursuit. CAG chrom 19 SCA 7: 5% - Ataxia, dysarthria, retinopathy, peripheral neuropathy, pyramidal signs, infantile phenotypes. Saccadic smooth pursuit, slow saccades. CAG chrom 3 SCA 8: 2-5% - ataxia, dysarthria, mild sensory neuropathy. Nystagmus, saccadic pursuit. CTG chrom 13 Exhibit anticipation

Question 39

Dx of an SCA

Answer 39

Initially suspected by the adult-onset of symptoms. MRI or CT of brain can detect atrophy (wasting) of the cerebellum and a variety of other subcortical structures. Molecular genetic test to determine gene that has the repeat can quickly ID other carriers in the family. Many of them can be confirmed by DNA testing. Once genetic defect is characterized, test family members

Question 40

SCA-3

Answer 40

Machado-Joseph Disease Most common SCA Most variable phenotype Pure cerebellar ataxia, familial parkinsonism, hereditary spastic paraplegia, herediatry neuropathy, and restless leg syndrome. Impaired temp discrimination in all limbs and even trunk and face is very specific for SCA3 but also pretty rare. Pseduoexophthalmos (bulging eyes caused by lid retraction) Faciolingual myokyma Dystonia

Question 41

Treatment of SCAs

Answer 41

No cure Supportive treatment Ultimately fatal. SCA 8 and 11 have normal lifespans. 6 and 11 are less severe.

Question 42

Treatment of TD

Answer 42

Benzos, baclofen, vitamin E Dopamine depleting agents like reserpine or tetrabenazine that do not block receptors have not be shown to cause TD.

Question 43

TD

Answer 43

Most common cause of TD is use of chronic dopamine blocking agents like typical antipsychotic agents. Note that all antipsychotics can do it. Also metoclopramide and other anti-nausea drugs. Generally develops months after beginning dopamine receptor blocking drugs Most freq causes Sterotypical movements of the mouth and surrounding regions Treatment is usually less than optimal and so the best course is to avoid TD altogether - constantly reassess need for and amount of dopamine blocking drugs Backward arching movement of neck (retrocolis) believed to strongly suggest TD

Question 44

Simple vs complex tics

Answer 44

Simple motor tics involve single groups of muscles. This causes jerk movements in cases of clonic tics, or briefly sustained posture in cases of dystonic or tonic tics Simple clonic - blinking, head/limb jerks, nose twitching Simple dystonic - oculogyric deviation, bruxism, blepharospasm, torticlois-like posturing Most common tonic tics are abdominal and other muscle tensing Simple phonic tics - coughing, sneezing, throat clearing, grunting, others Complex motor tics include coordinated movements which involve multiple muscle groups and often resemble normal movements. They vary from head shaking to touching and hitting. A complex tic should be considered a compulsion if it is preceded by obsessive thought, anxiety or fear. Complex tics are often hidden by incorporating them into seemingly planned and purposeful movement. Complex phonic tics include linguistically meaningful verbalizations. Although rare, coprolalia (bad words) can be seen. More common is repetition of someone elses or own words (echolalia or palilalia). Bad motor tic equivalent (middle finger) is copropraxia