1. Case Conference Ruth C. Rubio, MD November 25, 2009

2. Case Presentation Chief Complaint: “I can’t control the muscles in my arms.”

3. HPI: • 11-year old male c/o brief episodes of spastic movement of arms, exacerbated by running and other activities. • When he gets up suddenly or when he’s running, his arms flex and move around slowly similar to a snake. • Eyes also move funny but legs are not involved.

5. HPI: • Usually lasts ~4 seconds. • Started around a year ago but becoming more frequent. • When he thinks about the movements, they were more likely to occur. • No altered sensorium. • No other symptoms.

6. ROS: • (+) occasional headaches • (-) fever, staring spells, visual problems • (-) cough, DOB, rhinorrhea, otorrhea • (-) conjunctivitis, drooling • (-) diarrhea, constipation • (-) changes in UO • (-) cyanosis

7. PMH • Allergic Rhinitis - on Nasonex • Mild Persistent Asthma – no ICU, no ETT, no hospitalizations, on Flovent, Claritin, Albuterol prn • Allergies: dust mites, pollen, roaches

8. Birth History • Born FT, NSVD, BW 8 lbs ½ ounces • No complications • Unremarkable nursery course • Negative prenatal labs/maternal serologies

9. Developmental • In 6th grade, PS 59 Student Council • Plays basketball • Likes Irish dancing

11. Immunization • IUTD as per mom Social History • Lives with mom • Goes to his father every weekend

12. Family History (+) Epilepsy – maternal great uncle (+) ANA - mom with similar movements – started at 12 y/o, worse when dancing

14. Physical Exam VS: WNL, alert, awake, active No dysmorphic features/neurocutaneous stigmata (+) bilateral nasal congestion Neuro exam: fluent, alert, interactive CN II-XII – intact Motor – full and symmetric strength, no atrophy Cerebellar – no ataxia/dysmetria Reflexes – 2+, no clonus, no Babinski Sensation – intact Gait – normal Tone - normal

15. Labs: CBC: 8.5\13.6 / 208 /39.1\ N 43 L 36.7 CMP: 139|103| 16 /63 4 | 27 | 0.6 \9.4 4.3 | 19 | 0.5 6.9 | 26 | 380 U/A: WNL

16. Labs • ESR – 4 • ANA – negative • TSH – 2.7 • T4 – 6.9 • Ceruloplasmin – 31

17. Imaging • MRI - normal • EEG - normal

18. Outline • Definition of Terms • Review (motor systems) • Movement Disorders • Case Diagnosis • Case Discussion • Videos

19. Definition of Terms • Athetosis - slow writhing motions of the arms and hands that appear to flow into one another • Chorea – combination of jerky, arrhythmic, "dancelike" movements that may involve the whole body • Ataxia - lack of coordination while performing voluntary movements

20. Definition of Terms 4. Dystonia - increased muscle tone with repetitive, twisting, patterned movements and distorted posturing 5. Ballismus - uncontrollable flinging movements of an arm, a leg, or both

21. Motor Systems Cortex Cerebellum and the basal ganglia Brainstem Spinal cord Muscles

28. "Movement disorders are frequently misdiagnosed because there is not enough awareness of the differences in the disorders." - Dr. Albright

29. Pediatric Movement Disorders • Ataxiainability to make smooth, accurate, and coordinated movements, often due to disease of the cerebellum. • Bradykinesiaextreme slowness and stiffness of movement, often due to parkinsonian syndromes.

30. Pediatric Movement Disorders • Chorea and Choreoathetosissyndrome of continuous random movements that usually occur at rest and may appear to be fidgety, dancing, or writhing. • Dystoniaabnormal muscle contractions that lead to twisting, jerking, spasms, or stiffening at rest or during attempts at movement.

31. Pediatric Movement Disorders • Spasticityan increase in muscle stiffness, worsens w/ rapid movement and may be a/w increased reflexes and weakness, often d/t cerebral palsy. • Ticsrepetitive, stereotyped, and sometimes complex involuntary movements or sounds that may appear similar to purposeful actions.

32. Pediatric Movement Disorders • Myoclonusa condition of very rapid and brief shock-like jerks. • Psychogenic Disordersspan the full range of possible symptoms, including tremor, dystonia, ataxia, bradykinesia, and chorea. • TremorTremor is a rhythmic back-and-forth shaking at rest or with movement.

33. Back to the Case What’s the diagnosis?

34. Familial Paroxysmal Kinesigenic Dyskinesia

35. ParoxysmalDyskinesias • Paroxysmal - abnormal movements are sudden and unpredictable, with a relatively rapid return to normal motor function and behavior • Hyperkinesias - sudden episodes of abnormal involuntary movements

36. Classification • Paroxysmal kinesigenicdyskinesia (PKD) • Paroxysmal non-kinesigenicdyskinesia (PNKD) • Paroxysmal exertion-induced dyskinesia • Paroxysmal hypnogenicdyskinesia

37. Paroxysmal KinesigenicDyskinesia (PKD) • Age of onset: typically in childhood and adolescence, but ranges from four months to 57 years • Male predominance • associated with infantile, but not adult-onset seizures.

38. Paroxysmal KinesigenicDyskinesia (PKD) • unilateral or bilateral involuntary movements • precipitated by other sudden movements such as standing up from a sitting position, being startled, or changes in velocity • attacks include combinations of dystonia, choreoathetosis, and ballism

39. Paroxysmal KinesigenicDyskinesia (PKD) • Sometimes preceded by an aura • No loss of consciousness. • Can be as frequent as 100/day to as few as 1/month. • Usually a few seconds to 5 minutes in duration but can last several hours.

40. Genetics • Autosomal dominant with incomplete penetrance • Localized to chromosome 2q and chromosome 16cen • PKC and episodic ataxia type 1 with mutations of the KCNA1 gene. • PKC and infantile convulsions linked to chromosome 16cen near ion channel genes

41. Genetic Counseling Risk to Family Members: • Parents of a proband - > 90% of individuals w/ an affected parent Sibs of a proband • depends on the status of the parents. • f (+), risk is 50%. Asymptomatic carrier • Risk is 50%

42. Diagnosis • based on the clinical findings of attacks of dystonia, chorea, ballismus, or athetosis triggered by sudden movements that occur many times per day and can be prevented or reduced in frequency by phenytoin or carbamezepine.

43. Evaluation • EEG • MRI

44. Treatment • Phenytoin or Carbamezepine • Oxcarbazepine, Ethosuximide, Lamotrigine and Gabapentin * Lower dose than usual anti-epileptic range, same side effects

46. Paroxysmal NonkinesigenicDyskinesia (PNKD) • nonkinesigenic - not triggered by sudden movement • 1 in 5 million people • Autosomal dominant • Mutations in the PNKD gene (function of the protein is unknown)

47. Paroxysmal NonkinesigenicDyskinesia (PNKD) • NOT induced by exercise or sudden movement and do not occur during sleep • develop without a known cause • brought on by alcohol, caffeine, stress, fatigue, menses, or excitement

48. Paroxysmal NonkinesigenicDyskinesia (PNKD) • PNKD gene - similar to a protein that helps break down a chemical called methylglyoxal (found in alcoholic beverages, coffee, tea, and cola) • Research has demonstrated that this chemical has a toxic effect on neurons

50. Paroxysmal exercise-induced dystonia (PED) • Rare genetic disorder • Episodes of dystonia mostly affecting the feet induced by continuous exercise like walking or running. • Pathophysiology is unknown • Antiepileptic drugs are generally unhelpful