Download Paroxysmal movement disorders

Paroxysmal movement disorders
-Paroxysmal kinesigenic dyskinesia: Triggered by sudden movement. Short-lasting and frequent. Phenytoin or
carbamazepine is treatment. Associated gene: PRRT2.
-Paroxysmal NON-kinesigenic dyskinesia: NOT triggered by movement, but by other triggers or at rest
spontaneously. Long-lasting and infrequent. Klonopin is treatment. Associated gene: MR-1.
-Paroxysmal exercise-induced dyskinesia: Triggered by SUSTAINED exercise/physical exertion. Treatment not
great. Associated gene: SLC2A1.
-NOTE: sometimes genes associated with one type can be seen in phenotype of another type.
1) Paroxysmal kinesigenic dyskinesia/dystonia:
Pathophysiology:
-Presumed channelopathy (hence its excellent response to anti-epileptics, and association with infantile
convulsions)
-65-75% have clear AD family history of similar symptoms, most times with complete penetrance.
-Associated with PRRT-2 gene (though other genes may be involved).
Signs/symptoms:
-Age of onset: Average 10 years, range 1-40 years. Rare to be >18 years old.
-Trigger: Sudden voluntary movement elicits the abnormal movement; other rarer triggers include
anxiety/startle, intention to move/acceleration, coffee, sleep deprivation.
-Aura: Tingling, odd feeling 50% of time.
-Frequency: Many attacks per day (typically 1-100’s), though rarely can be as infrequent as 1-2 per year.
-Duration: Average 34 seconds, VERY rarely >20 minutes.
-Movement type: mixed (67%) > dystonia (17%) > chorea (15%) >ballismus (1%). Can be bilateral > unilateral.
Can involve the face, sometimes associated with dysarthria.
Workup
-Obtain CMP and baseline MRI brain to rule out secondary causes (MS, vascular disease, tumor, etc)
-May consider testing for PRRT-2 gene. Also consider whole exome sequencing.
DDx:
-Seizure, psychogenic, hypo/hyperglycemia, Dopa-responsive dystonia, limb shaking TIA.
Dx criteria:
-Identified trigger (sudden movement >>startle) + short duration (vast majority are seconds to <1 minute,
though rarely can last as long as 20 minutes) + age of onset <20 (unless family hx, as some cases can start as
late as age 33) + no LOC/pain during attack + normal exam in between attacks + control of attacks with
carbamazepine or phenytoin.
-One possible causative gene is PRRT2, but many patients have PKD without this gene, suggesting other
causative genes not yet found.
Tx:
-Phenytoin (100-200mg daily) or carbamazepine (50-600mg daily); often responds quite well (85% are
responders) to even low doses. Some suggestion that Diamox or Topamax may also be helpful.
-Prognosis: 25% remit spontaneously; another 25% had marked improvement with time (ie, by age 30)
2) Paroxysmal NON-kinesigenic dyskinesia/dystonia:
Pathophysiology:
-AD, with high penetrance.
-Due to mutation in MR-1 gene. Consider whole exome sequencing.
Signs/symptoms:
-Age of onset: Mean 5 years, range 6 months to 35 years (RARE to have onset > age 18)
-Trigger: NOT movement; classically alcohol, caffeine, or strong emotion/stress that elicits the abnormal
movement, though sometimes may have no clear trigger at all.
-Aura: Sometimes present. Tightness in a limb, odd mouth movements, SOB, migraine, or anxiety.
-Frequency: Few times a year (though can cluster a few times in a week); most (77%) report at least 1
attack/week.
-Duration: Usually last 10-60 minutes, but can last up to 12 hours; rarely < 1 minute.
-Movement Type: dystonia AND chorea (65%); less commonly dystonia (27%) or chorea (2.7%) by itself. Can
involve face. May be associated with dysarthria/anarthria with retained awareness.
Workup
-Obtain CMP and baseline MRI brain to rule out secondary causes (MS, vascular disease, tumor, etc)
-May consider gene testing for MR-1.
DDx:
-Psychogenic, Dopa-responsive dystonia, seizure.
Tx:
-Avoid triggers
-Klonopin is treatment of choice (80-90% of patients had good response)
-Anti-epileptics are not effective
3) Paroxysmal exercise-induced dyskinesias/dystonia:
Pathophysiology:
-Extremely rare, only about 30 reported cases.
-Can associated with epilepsy
-Associated with gene SCL2A1 (though other genes may also be the culprit). Consider whole exome
sequencing.
Signs/symptoms:
-Age of onset: mean of 8.6 years old, range 1-49 years old, but RARE to have onset >age 18 years.
-Trigger: Sustained exertion, usually lasting 5-15 minutes; more rare triggers are fasting, stress, or anxiety.
-Aura: None
-Frequency: Usually several attacks per week.
-Duration: Mean 15-40 minutes (can last up to several hours, very rare to last less than 5 minutes). Resolve
within 10 minutes of stopping exercise.
-Movement types: Almost always mixed dystonia-chorea (95%). Can be associated with migraines or epilepsy
or ataxia.
Workup
-Obtain CMP and baseline MRI brain to rule out secondary causes (MS, vascular disease, tumor, etc)
-May consider gene testing for SLC2A1.
DDx:
-Psychogenic, Dopa-responsive dystonia, seizure.
Tx:
-Antiepileptics don’t work well, aside from maybe gabapentin
-Some evidence for ketogenic diet
Gene-testing algorithm:
Review articles:
1) Bhatia, Kailash P. "Paroxysmal dyskinesias." Movement Disorders 26.6 (2011): 1157-1165.
2) Erro, Roberto, Una‐Marie Sheerin, and Kailash P. Bhatia. "Paroxysmal dyskinesias revisited: a review of 500
genetically proven cases and a new classification." Movement Disorders 29.9 (2014): 1108-1116.