Movement Disorders 4

Question 1

Dystonia definition

Answer 1

Παρατεταμένες ή διαλείπουσες μυικές συσπάσεις, οι οποίες προκαλούν ανώμαλες, συχνά επαναλαμβανόμενες κινήσεις, θέσεις ή και τα δύο.
Τα φαινομενολογικά χαρακτηριστικά των δυστονικών κινήσεων είναι:
* η σχετικά μεγάλη διάρκεια (σε σύγκριση με τον μυόκλονο και τη χορεία)
* η ταυτόχρονη σύσπαση αγωνιστών και ανταγωνιστών μυών
* η στροφική κίνηση του προσβεβλημένου μέρους του σώματος
* η συνεχής σύσπαση της ίδιας ομάδας μυών
* η εμφάνιση ή επιδείνωση των δυστονικών κινήσεων με την εκούσια κίνηση

Question 2

Dystonia classification by body distribution

Answer 2

1) focal dystonia, the abnormal movements involve a single body region

2) segmental dystonia affects two or more contiguous body parts

3) multifocal, two or more noncontiguous body areas are involved

Question 3

Types of dystonia

Answer 3

action dystonia: the dystonic movements are elicited only with voluntary movement

taskspecific dystonia (δυστονία εξειδικευμένου έργου): when dystonia is triggered only with particular actions

overflow (υπερχείλιση): activation of dystonic movements by actions in remote parts of the body; examples include leg dystonia while writing or axial dystonia with talking.

paradoxical dystonia: Dystonia that is suppressed by voluntary activity
example, talking or chewing may suppress dystonia
involving facial and oromandibular muscles (also known as
Meige syndrome).

Question 4

Factors that exacerbate or decrease dystonia

Answer 4

Factors that tend to exacerbate dystonia include fatigue and emotional stress

the movements usually decrease with relaxation or sleep.
Many patients discover a tactile or proprioceptive sensory trick (geste antagoniste) that minimizes the dystonia; for example, a patient with cervical dystonia may touch the chin.

Question 5

Which feature is suggestive of a secondary dystonia

Answer 5

Hemidystonia

Question 6

Which is the most common focal dystonia

Answer 6

cervical dystonia

Question 7

Cervical dystonia clinical findings

Answer 7

Various combinations of neck muscles may be involved to
produce abnormal head positions, including horizontal turning (torticollis), tilting (laterocollis), flexion (anterocollis), or extension (retrocollis).
Repetitive jerking of the head may resemble tremor, but can usually be distinguished by its directional preponderance. Approximately 75% of patients complain of neck pain.

Question 8

Blepharospasm clinical findings

Answer 8

Blepharospasm causes contraction of the orbicularis oculi;
mild cases are characterized by increased blink rate with a large number of of blinking, whereas more severely affected patients have visual impairment due to sustained forceful eye closure

Question 9

Is age at onset of dystonia prognostic

Answer 9

Yes

patients with onset of dystonia in childhood or adolescence
are likely to progress to generalized or multifocal dystonia,
especially when the dystonia initially involves the leg.

Question 10

Isolated and combined dystonias

Answer 10

https://www.uptodate.com/contents/image?imageKey=NEURO%2F59044&topicKey=NEURO%2F4886&search=dystonia&rank=1~150&source=see_link

Question 11

DYT1 dystonia: gene mutation, common ethnicity affected, pattern of inheritance, clinical findings

Answer 11

• mutation of the gene TOR1A located on the long arm of chromosome 9
• especially common in the Ashkenazi Jewish population,
  where its prevalence is 1 in 2000 persons

inherited in an autosomal dominant fashion, with reduced penetrance of 30%! (μόνο το 30% των ατόμων που φέρουν τη μετάλλαξη θα νοσήσουν)

• early-onset, generalized, persistent, isolated, inherited and dominant disorder.

It has a mean age at onset of 12.5 years and begins in a limb in 94% of cases.

It tends to progress to generalized dystonia; the probability of generalization is related to age and site of onset.

Question 12

Indication for genetic testing for DYT1 dystonia

Answer 12

Patients with onset of dystonia before 26 years of age as well as for patients with later onset who have a relative with early onset dystonia

Question 13

DYT6 dystonia: gene mutation, body distribution

Answer 13

• heterozygous mutations in the gene THAP1 of chromosome 8
• often involves the arms and axial muscles
• speech is also frequently affected due to oromandibular (στοματογναθική) or laryngeal involvement

Question 14

DYT1 and DYT6 dystonia clinical difference

Answer 14

In DYT 6 speech is also frequently affected due to oromandibular (στοματογναθική) or laryngeal involvement

Question 15

Dopamine responsive dystonia: gene mutation, pattern of inheritance classification (age of onset, body distribution, temporal pattern and associated clinical manifestations), which sex is mostly affected

Answer 15

• Most cases of DRD are caused
  by heterozygous mutations in the GTP-cyclohydrolase I (GCH1) gene located at 14q22.1 (DYT5)
  In addition to classic DRD due to heterozygous GCH1 mutations, DRD may result from homozygous or compound heterozygous mutations in GCH1, in genes for other enzymes involved in pterin metabolism, and in genes encoding tyrosine hydroxylase.
• Inheritance is autosomal dominant with reduced penetrance
• Typically, gait dysfunction (often appearing stiff-legged or spastic) begins in early or mid-childhood, and symptoms are worst late in the day and improve with sleep.
  Parkinsonism, including rigidity, bradykinesia, flexed posture, and loss of postural reflexes, may be prominent
• Girls are affected more often than boys.

Question 16

Dopamine responsive dystonia: diagnostic tests and management

Answer 16

Although the dystonia may improve dramatically with anticholinergic medications such as trihexyphenidyl, a trial of oral levodopa therapy at low doses (usually no more than 300–400 mg daily) is useful for diagnosis as well as for treatment.

Additional support for the diagnosis can be obtained from
* phenylalanine-loading test, in which blood levels of phenylalanine remain elevated for a prolonged period
* Measurement of biopterin metabolites in cerebrospinal fluid may also aid in diagnosis.

Question 17

Myoclonus dystonia (DYT11): gene mutation, pattern of inheritance, classification (age of onset, body distribution, temporal pattern and associated clinical manifestations), what improves symptoms

Answer 17

mutation in the epsilon-sarcoglycan (SGCE) gene on chromosome 7q21

Inheritance is autosomal dominant

Onset is usually in childhood or adolescence.
Combined dystonia syndrome with prominent myoclonic jerks, usually affecting the arms and trunk more than the legs.

The symptoms characteristically respond to alcohol, and alcoholism (as well as other psychiatric disorders) is not uncommon

Question 18

rapid onset dystonia-parkinsonism (DYT 12): gene mutation, pattern of inheritance, classification (age of onset, body distribution, temporal pattern and associated clinical manifestations)

Answer 18

19q13

autosomal dominant

dystonia and parkinsonism begin suddenly in adolescence or early adulthood and progress over hours to weeks, after which the symptoms usually stabilize

Question 19

When should a trial with lavodopa-carbidopa be done in patients with dystonia

Answer 19

1) all non-DYT1 patients with early onset of symptoms

2) late-onset patients with features suggesting DRD (ie, parkinsonism, diurnal variation).

Question 20

Dystonias for which genetic testing is commercially available

Answer 20

DYT1, DYT6, DRD (DYT5), and myoclonus-dystonia (DYT11)

(Also secondary dystonias including SCAs and PKAN)

Question 21

Treatment of dystonia in adults

Answer 21

1) levodopa trial – levodopa trial is suggested for most adults with idiopathic focal or generalized dystonia.

2) Cervical dystonia – BoNT injections are the mainstay of therapy for cervical dystonia.
Oral medications are used in patients who cannot receive injections and for those with an inadequate response to first-line therapy

3) Other focal dystonias – For adults with blepharospasm, focal upper limb dystonia (including writer’s cramp), and adductor spasmodic dysphonia (adductor laryngeal dystonia), BoNT injection therapy is recommended

4) Role of oral medications – Symptomatic medication trials play a role in adults with generalized dystonia and those with focal dystonias who do not have access to BoNT therapy

For most adults with refractory generalized dystonia, first-line therapy with a benzodiazepine such as clonazepam is suggested
Low doses of trihexyphenidyl or baclofen are alternative second-line therapies

A vesicular monoamine transporter type 2 (VMAT2) inhibitor such as tetrabenazine may be beneficial for adults with debilitating generalized isolated dystonia, although careful monitoring for side effects, including depression, is necessary.

5) Refractory dystonia – For adults with debilitating generalized dystonia or other types of focal/segmental isolated dystonia who do not respond to oral pharmacologic therapy or BoNT injections, consideration of bilateral DBS of the GPi is suggested

Question 22

Dystonic storm or status dystonicus

Answer 22

a rare but life-threatening disorder that may occur in primary or secondary dystonia, especially in children or adolescents with underlying generalized dystonia.

Severe repeated dystonic spasms may interfere with respirations and cause hyperpyrexia, dehydration, and acute renal failure secondary to rhabdomyolysis

Question 23

Tetrabenazine: mechanism of action and adverse effects

Answer 23

reversible inhibitor of the human vesicular monamine transporter type 2 (VMAT-2) and thereby decreases the uptake of monoamines (including dopamine, serotonin, norepinephrine, and histamine) into synaptic vesicles and depletes the monoamine stores

• Tetrabenazine can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington disease!!
• Drug-induced Parkinson’s disease
• Central nervous system: Drowsiness, sedation, depression, fatigue, insomnia, akathisia, anxiety, falling
• Gastrointestinal: Nausea
• Respiratory: Upper respiratory tract infection

Question 24

Wilson disease: cause, clinical features, diagnosis

Answer 24

Wilson disease is an autosomal recessive disorder and is the result of mutation in ATP7B, a gene encoding a copper transport protein, ATP7B, on chromosome 13

Reduced biliary excretion of copper results in its accumulation in the liver and other tissues (eg, brain, cornea).
Most patients have liver involvement that may range from asymptomatic abnormalities in liver biochemistries (eg, elevated serum aminotransferases) to cirrhosis to acute liver injury/failure

Clinical findings:
Most patients with Wilson disease are diagnosed between the ages of 3 and 55 years

The spectrum of presentation ranges from asymptomatic patients to those with symptoms related to liver, neurologic and/or psychiatric involvement:

• Liver disease – (ranges from asymptomatic abnormalities in liver biochemistries to cirrhosis or acute liver injury)
• Neurologic symptoms – (dysarthria and movement disorders (eg, gait abnormalities, dystonia, tremor “wing-beating”, parkinsonism, ataxia, dementia)
• Psychiatric symptoms – (mood disorders, psychosis, sleep disturbance, and cognitive changes)
• Other manifestations – (Kayser-Fleischer rings and Coombs-negative hemolytic anemia)

Diagnostic evaluation:
Initial diagnostic testing includes
1) an ocular slit-lamp examination (or anterior segment optical tomography),
2) 24-hour urinary copper excretion, and serum ceruloplasmin.

Liver biopsy is not always necessary because the diagnosis can be established in some patients with noninvasive testing and ocular examination

For patients in whom the diagnosis remains suspected but not established based on initial testing, additional studies include liver biopsy to assess hepatic copper concentration and/or molecular genetic testing to evaluate for pathogenic (disease-causing) variants affecting both ATP7B alleles.

https://www.uptodate.com/contents/image?imageKey=GAST%2F104976&topicKey=GAST%2F83837&search=wilson%20disease&rank=1~150&source=see_link

https://www.uptodate.com/contents/image?imageKey=GAST%2F141163&topicKey=GAST%2F83837&search=wilson%20disease&rank=1~150&source=see_link

Question 25

Wilson disease: treatment and prognosis

Answer 25

Patients with Wilson disease require lifelong therapy.
Discontinuation of therapy can lead to the development of acute liver failure or other symptoms.
Treatment should be given in two phases: stabilizing the patient by removing tissue copper that has accumulated and then preventing reaccumulation (maintenance).

● Asymptomatic patients – In asymptomatic patients identified through screening, treatment with a chelating agent (such as D-penicillamine or trientine) is remommended
Zinc may be used in patients who are reluctant to use a chelating agent or who are intolerant of them, but liver biochemical test should be monitored at least every four months and a chelating agent added if these tests worsen.
Evolving consensus has been to use trientine because of its relatively favorable side-effect profile.
Copper balance should be monitored regularly in such patients by obtaining a 24-hour urine collection and by estimating nonceruloplasmin bound copper.

● Symptomatic patients – Symptomatic patients should be treated with a chelating agent (D-penicillamine or trientine) until stable.
Trientine may be preferred because it has fewer side effects than D-penicillamine and appears to be less likely to exacerbate neurologic symptoms.

Patients typically require six months to five years of higher-dose treatment, after which they can be transitioned to maintenance therapy.
Prior to the transition, patients should be clinically well, have normal serum aminotransferases, and hepatic synthetic function, non-ceruloplasmin-bound copper in the normal range (<15 mcg/dL or 150 mcg/L), and 24-hour urinary copper repeatedly in the range of 200 to 500 mcg (3 to 8 micromoles) per day.
Maintenance therapy can be achieved with zinc or with lower doses of a chelator, and patients should be monitored regularly as described above.

● Acute liver failure – Patients presenting with acute liver failure due to Wilson disease require liver transplantation. Plasmapheresis, exchange transfusion, hemofiltration, molecular absorbant recirculating system (MARS), or dialysis may be performed while transplant is being awaited.
Albumin dialysis may also be beneficial, but experience is limited.
Recovery with supportive therapy has been described

Question 26

Dystonia in Wilson disease characteristics

Answer 26

• Neurological complications usually affects adult-onset patients
• Dystonia can be generalized, segmental, or multifocal
• cranial involvement is characteristic

Question 27

When to suspect wilson disease

Answer 27

Wilson disease may be suspected in patients with any of the following

*Unexplained liver biochemical abnormalities (eg, elevated aminotransferases), especially if they are accompanied by neurologic or psychiatric symptoms.

*Low ceruloplasmin (<20 mg/dL [<200 mg/L] with higher suspicion if ceruloplasmin is <14 mg/dL [<140 mg/L]).

*A first-degree relative with Wilson disease.

*Other feature suggestive of copper overload (eg, chronic liver disease of uncertain etiology, unexplained neurologic symptoms such as dysarthria, gait abnormality).

Question 28

Neurological adverse effects of treatment with D - penicillamine for Wilson disease

Answer 28

neurological deterioration (10%!)
myasthenia gravis
neuropathy

Guillain-Barre syndrome
Anxiety
agitation
dystonia
hyperpyrexia

Question 29

Pantothenate kinase-associated neurodegeneration (PKAN): cause, pathology, clinical findings, imaging, diagnosis

Answer 29

autosomal recessive disorder; most cases are caused by mutations in the gene encoding pantothenate kinase 2 (PANK2)

KAN is included in a group of disorders known as neurodegeneration with brain iron accumulation

Classic PKAN present in the first decade of life with extrapyramidal signs including orofacial and limb dystonia, dysarthria, rigidity, and choreoathetosis.
Retinopathy, spasticity, and cognitive decline are common.
Acanthocytosis occurs in just 8 to 10 percent.
Less commonly, patients may present later in life (in the second decade) with more prominent rigidity and a slower progression.
In such patients, the clinical syndrome overlaps with juvenile-onset Huntington disease, Huntington disease-like 2 (HDL2), and chorea-acanthocytosis.

On brain MRI, iron deposition in the globus pallidus creates a hallmark “eye of the tiger” sign in these patients, which can be diagnostic.

Sequence analysis of the PANK2 gene is commercially available to confirm the diagnosis.

Question 30

Neurologic adverse effects of dopamine receptor antagonists

Answer 30

Acute reactions
* Acute dystonia
* Acute (or subacute) akathisia

Drug-induced parkinsonism

Neuroleptic malignant syndrome

Tardive syndromes
* Classical tardive dyskinesia
* Tardive dystonia
* Tardive akathisia

Question 31

Dopamine receptor blocking agents

Answer 31

Question 32

What increases the risk of developing a tardive syndrome and which antipsychotics have little/ or no risk

Answer 32

The risk of developing a tardive syndrome is related to
the avidity of D2 receptor binding and blockade

The only antipsychotic agents that appear
to have little or no risk of inducing a tardive syndrome are
(1) clozapine and quetiapine, which have weak affinity for
D2 receptors and appear to exert their antipsychotic effects
through serotoninergic mechanisms, and
(2) pimavanserin, indicated for treating psychosis in PD, which exerts inverse agonist and antagonist activity at serotonin 2A receptors (5-HT2A) receptors.

Question 33

Acute dystonia after dopamine receptor blocking agent: clinical findings and management

Answer 33

The onset of symptoms ranges from immediately after the first dose to several days of treatment.
In about half of the cases, the acute dystonic reaction occurs within 48 hours, and in 90% by 5 days after starting the therapy.

Acute dystonic reactions most often affect the ocular muscles (oculogyric crisis), face, jaw, tongue, neck and trunk, and less often limbs.
A typical acute dystonic reaction may consist of head tilt backward or sideways with tongue protrusion and forced opening of the mouth, often with arching of trunk and ocular deviation upward or laterally.

In patients with acute dystonic reactions, symptoms can be relieved within minutes using parenteral anticholinergics or antihistaminics.
Intravenous diazepam is also effective and can be used as an alternative therapy. If untreated, the majority of cases resolve spontaneously within 12 to 48 hours after the last dose of the offending agent.

Question 34

Acute akathesia after dopamine receptor blocking agent management

Answer 34

Acute akathisia is self-limited, disappearing on discontinuation of the offending neuroleptic.
Acute akathisia can be controlled by anticholinergics when neuroleptics need to be continued;
other agents that can reduce akathisia include β-blockers, clonidine, and mirtazapine.

Question 35

Drugs that cause parkinsonism

Answer 35

• First-generation antipsychotics
• Second-generation antipsychotics
• Antiemetic and prokinetic medications
• Dopamine-depleting agents — Tetrabenazine, deutetrabenazine, and valbenazine
• Valproic acid
• SSRis
• Lithium
• Calcium channel blockers – Cinnarizine and flunarizine

Question 36

Tardive dyskinesia definition

Answer 36

continuous, repetitive, rhythmical, stereotypic movements involving oral, buccal, and lingual areas.

Question 37

Tardive dyskinesia clinical findings

Answer 37

Repetitive, complex chewing motions, occasionally with lip-smacking and opening of the mouth, tongue protrusion, lip pursing, and sucking movements.

The mouth movements in classical tardive dyskinesia are readily suppressed by patients when they are asked to do so, and they cease during talking or eating.

The constant lingual movements may lead to tongue hypertrophy, and macroglossia is a common clinical sign. Tardive dyskinesias may also cause limb movements, usually distal, repetitive, patterned choreic movements of the toes and fingers, the latter sometimes termed piano-playing movements.
Sometimes, there is rhythmic rocking of the trunk.

Question 38

Tardive dyskinesia differential diagnosis

Answer 38

• Huntington disease
• idiopathic dystonia of the face (primary oromandibular dystonia, or Meige syndrome)
• senile chorea of the face
• branchial myoclonus
• facial tics
• myokymia

Question 39

Tardive dyskinesia management

Answer 39

●Symptomatic therapy –
Mild TD may not be sufficiently bothersome to require treatment and its associated side effects.
For patients with moderate to severe TD, tetrabenazine and botulinum toxin injections are the main symptomatic therapies

Benzodiazepines are sometimes helpful for mild symptoms but are unlikely to help more severe TD

●Refractory dyskinesia – Patients with permanent, disabling TD may be candidates for surgical therapy with deep brain stimulation

Question 40

Neuroleptic malignant syndrome: cause and risk factors

Answer 40

The cause of NMS is unknown

Risk factors:
1) Associated medications are antipsychotic and antiemetic agents

2) Antiparkinson medication withdrawal — NMS is also seen in patients treated for parkinsonism in the setting of withdrawal of L-Dopa or dopamine agonist therapy, as well as with dose reductions and a switch from one agent to another
Infection, dehydration, and surgery are possible precipitants as well

Question 41

Neuroleptic malignant syndrome: time of symptoms after treatment onset

Answer 41

While symptoms usually develop during the first two weeks of antipsychotic therapy, the association of the syndrome with drug use is idiosyncratic
NMS can occur after a single dose or after treatment with the same agent at the same dose for many years

Question 42

Neuroleptic malignant syndrome: clinical findings

Answer 42

● Mental status change
- the initial symptom in 82 percent of patients
- often takes the form of an agitated delirium with confusion rather than psychosis
- catatonic signs and mutism can be prominent
- evolution to profound encephalopathy with stupor and eventual coma is typical

● Muscular rigidity
Other motor abnormalities include tremor, and less commonly, dystonia, opisthotonus, trismus, chorea, and other dyskinesias. Patients can also have prominent sialorrhea, dysarthria, and dysphagia.

● Hyperthermia

● Autonomic instability
- tachycardia
- labile or high blood pressure
- tachypnea
- Dysrhythmias
- Diaphoresis

Question 43

Neuroleptic malignant syndrome: diagnosis and treatment

Answer 43

• Antipsychotic agents should be withheld if there is suspicion for NMS. Patients should have close inpatient monitoring of clinical signs and laboratory values
• Patients with significant hyperthermia and rigidity should be admitted to an intensive care unit setting and undergo aggressive supportive care, as well as monitoring for potential dysautonomia and other complications
• For patients with creatine kinase elevations or hyperthermia on presentation and those who do not respond to withdrawal of medication and supportive care within the first day or two, medical therapy is suggested

Benzodiazepines are typically initiated first to mitigate agitation and/or muscle rigidity; dantrolene and/or bromocriptine may be added depending on symptom severity

• Electroconvulsive therapy is an option in patients not responding to medical therapy in the first week, those in whom residual catatonia persists after other symptoms have resolved, and those in whom lethal catatonia is suspected as an alternative or concomitant disorder

Question 44

Medical treatment of neuroleptic malignant syndrome

Answer 44

1) Benzodiazepines
Lorazepam is used 1 to 2 mg IM or IV every four to six hours.
Diazepam is dosed as 10 mg IV every eight hours.

2) Dantrolene
- a direct-acting skeletal muscle relaxant and is effective in treating malignant hyperthermia.
- Doses of 1 to 2.5 mg/kg IV are typically used in adults and can be repeated to a maximum dose of 10 mg/kg/day.
- There is associated risk of hepatotoxicity, and dantrolene should probably be avoided if liver function tests are very abnormal.
- While some recommend discontinuing it after a few days, others suggest continuing for 10 to 14 days followed by a slow taper to minimize risk of relapse

3) Bromocriptine
- a dopamine agonist
- Doses of 2.5 mg (through nasogastric tube) every six to eight hours are titrated up to a maximum dose of 40 mg/day
- It is suggested that this be continued for 7 to 14 days after NMS is controlled and then tapered slowly

4) Amantadine
- has dopaminergic and anticholinergic effects and is used as an alternative to bromocriptine
- an initial dose is 100 mg orally or via gastric tube and is titrated upward as needed to a maximum dose of 200 mg every 12 hours

Question 45

Common laboratory finding in neuroleptic malignant syndrome

Answer 45

Increased CPK >1000

Question 46

When should antipsychotics restart after neuroleptic malignant syndrome?

Answer 46

If antipsychotic medication is required, the following guidelines may minimize risk of NMS recurrence

● Wait at least two weeks before resuming therapy, or longer if any clinical residua exist.

● Use lower- rather than higher-potency agents.

● Start with low doses and titrate upward slowly.

● Avoid concomitant lithium.

● Avoid dehydration.

● Carefully monitor for symptoms of NMS.

Question 47

Neuroleptic malignant syndrome mortality rate

Answer 47

20-30%

Question 48

Restless leg syndrome: usual age of onset, time of the day characteristic, prevalence

Answer 48

usually begins during middle age and worsens with time.

RLS is a circadian disorder that typically begins in the evening and may progressively worsen during the night

3–10% of individuals

Question 49

Restless leg syndrome: risk factors

Answer 49

1) iron-deficiency anemia
2) uremia
3) peripheral neuropathy
4) Spinal cord disorders
5) Pregnancy
6) Multiple sclerosis

Question 50

Restless leg syndrome: clinical findings

Answer 50

• discomfort or unusual sensations (“dysesthesias”) in the legs, sometimes described as intolerable tingling, crawling, creeping, stretching, pulling, or prickling sensations
• The legs are invariably involved, usually bilaterally, whereas the trunk and arms are rarely affected.
• RLS typically occurs during rest or sleep, or when patients are drowsy
• The discomfort is associated with an irresistible urge to move the legs or walk about, which immediately relieves the unpleasant sensations.

Question 51

Restless leg syndrome: diagnostic criteria

Answer 51

RLS is a clinical diagnosis that should be suspected in patients who complain of an urge to move the legs when lying in bed or sitting down, particularly if the symptom occurs predominantly in the evenings

The diagnosis is made by history and does not require additional testing, except for an assessment of iron stores in all patients and blood urea nitrogen and creatinine if uremia is suspected.

Question 52

Restless leg syndrome: exacerbating factors

Answer 52

● Antihistamines

● Dopamine receptor antagonists, including antipsychotic medications and many anti-nausea medications (eg, prochlorperazine, chlorpromazine, metoclopramide).

● Certain antidepressants, including mirtazapine and possibly tricyclic antidepressants, selective serotonergic reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs)
SSRIs, however, are more consistently associated with periodic limb movements of sleep than RLS

Question 53

Restless leg syndrome: management

Answer 53

● Check iron stores

● Behavioral strategies – Patients should be counseled to avoid aggravating drugs and substances such as caffeine. Mental alerting activities, exercise, leg massage, and applied heat often help RLS. In patients with mild and/or intermittent symptoms, these therapies may be sufficient for symptom relief

● On-demand therapy for intermittent symptoms – In patients with intermittent symptoms that are not frequent enough to require daily therapy but are nonetheless disabling when they do occur (eg, long car rides, occasional bedtime flares), a trial of carbidopa-levodopa on an as-needed basis is suggested. One 25/100 mg tablet (or half a tablet) has rapid onset, good tolerability, and is unlikely to cause augmentation when used in this manner

● First-line daily medication – In most patients with chronic persistent RLS (ie, symptoms ≥2 days per week and significantly impacting quality of life), initial therapy with a gabapentinoid (pregabalin or gabapentin) rather than a dopamine agonist is suggested.

A dopamine agonist (pramipexole, ropinirole, or rotigotine) is a reasonable first-line alternative

Question 54

Which medical treatment is prefered in restless leg syndrome and why

Answer 54

to start with a gabapentinoid is preferred, to avoid the risk of augmentation and impulse control disorders with dopamine agonists

a dopamine agonist is an alternative in patients at increased risk for side effects from a gabapentinoid, such as those with obesity and its complications, a past or present history of moderate or severe depression, disorders causing gait instability or respiratory failure, or a history of substance use disorder

Question 55

What is augmentation in restless leg syndrome and how it is managed

Answer 55

Augmentation refers to an overall worsening of symptom severity while taking a dopaminergic medication for RLS.
Management generally involves reduction or elimination of the causative agent and substitution of other medications

Question 56

Which is the most common complication of treatment with dopamine agonist in RLS

Answer 56

Augmentation (worsening of symptom severity)

Question 57

Tourette syndrome treatment

Answer 57

https://www.uptodate.com/contents/image?imageKey=NEURO%2F143357&topicKey=NEURO%2F126069&search=tics&rank=2~105&source=see_link

Question 58

Primary tic disorders and criteria

Answer 58

Question 59

Treatment of myoclonus

Answer 59

• Cortical myoclonus – For patients with debilitating cortical myoclonus, we suggest levetiracetam as initial therapy. Piracetam, clonazepam, valproate, and perampanel are reasonable alternatives for initial or add-on therapy.
• Cortical-subcortical myoclonus – Cortical-subcortical myoclonus occurs primarily in association with generalized epilepsy syndromes (JME valproate)
• Subcortical-nonsegmental myoclonus – For patients with subcortical-nonsegmental myoclonus (eg, essential myoclonus, myoclonus-dystonia syndrome, reticular reflex myoclonus, hyperekplexia, or propriospinal myoclonus), we suggest initial treatment with clonazepam. Zonisamide is an alternative for myoclonus-dystonia and should be tried if there is insufficient improvement with clonazepam. Benztropine and trihexyphenidyl are additional options for essential myoclonus.
• Palatal myoclonus – Palatal myoclonus is typically refractory to oral medications and can be debilitating, most commonly from the clicking noise that it creates. For debilitating palatal myoclonus, we suggest treatment with botulinum toxin injections. Injections are typically administered by an otolaryngologist with experience in treating myoclonus.
• Spinal segmental myoclonus – For spinal segmental myoclonus, we suggest clonazepam as initial treatment Botulinum toxin injections are sometimes helpful as an alternative.
• Hemifacial spasm – For most patients with disabling hemifacial spasm, we suggest treatment with botulinum toxin injections rather than oral medications.
  Injections should be performed by a practitioner or center with the necessary anatomic and technical expertise

Question 60

antiseizure medications that can worsen cortical or cortical-subcortical myoclonus

Answer 60

Certain antiseizure medications can worsen cortical or cortical-subcortical myoclonus, particularly in progressive myoclonic epilepsy syndromes.
These agents include phenytoin, carbamazepine, oxcarbazepine, lamotrigine, vigabatrin, tiagabine, gabapentin, and pregabalin