Muscular dystrophy & cerebral palsy

Question 1

Muscular Dystrophy (MD)

Answer 1

• Inherited myopathic disorders characterized by progressive weakness
  and wasting

Question 2

Different types of Muscular dystrophy

Answer 2

– Duchenne
– Becker
– Limb-Girdle
– Facioscapulo-humeral
– Emery-Dreifuss
– Distal
– Ocular
– Oculopharyngeal
– Myotonic dystrophy

Question 3

Duchenne Dystrophy epidemiology

Answer 3

– Rare muscle disorder, one of the most frequent genetic conditions
affecting approximately 1 in 3,500 male births worldwide.
– Average Age of diagnosis: 5 years old (3-6yo)
* About 2.5 years from initial symptoms to diagnosis
– More than 30 forms of MD, Duchenne is the most common
– >90% of people with the disease are in wheelchairs by age 15

Question 4

The Role of Dystrophin in duchenne dystrophy

Answer 4

– Protein coded by DNA→RNA→Protein
– Anchor complex of other proteins responsible for communication with the extracellular matrix (eg. Ca++)
– Malformation or absence can cause gaps in cell membrane
– Decreased function of muscle cells and lead to death of cells

Question 5

Duchenne Dystrophy clinical presentation

Answer 5

– Proximal muscle weakness
– Thin, weak thighs
– Weak gluteal muscles
– Pseudohypertophy “fat calves”
– Tip toe walking
– Poor balance
– Shoulders and arms held back
– Gower’s sign (walk up body to stand)
– 1/3 of pts have cardiomyopathy by
14 yo, virtually all pts by 18 yo
– Wheelchair dependent by 10-12 yo

Question 6

Duchenne Dystrophy diagnosis

Answer 6

– Clinical presentation leading to suspicion
– Muscle biopsy with immunostaining analysis of dystrophin
– DNA analysis for mutations on X chromosome
– Can also get a CK if suspicious, can be 100 x normal limit

Question 7

Duchenne Dystrophy treatment

Answer 7

– Supportive care
* PT for active and passive exercise, OT, Speech Therapy, Respiratory
Therapy
* Bracing limbs
– Medication
* Prednisone or deflazacort (corticosteroids)
– Surgery
* Mostly for scoliosis causing internal organ issues

Question 8

Becker Dystrophy

Answer 8

• Becker is very similar to Duchenne except…
  – Dystrophin gene is functioning, but abnormally.
  – Malformed Dystrophin is produced in low concentration
  – Think of a slow progressing Duchenne MD

Question 9

Becker Dystrophy presentation

Answer 9

– Same as Duchenne, but slower progression and slower onset.
– Pts may have normal lifespan

Question 10

Becker Dystrophy treatment

Answer 10

– Supportive care
– Medication
* Prednisone or deflazacort (corticosteroids)
– Surgery
* Mostly for scoliosis causing internal organ issues

Question 11

Myotonia = ____

Answer 11

Sustained contraction

Question 12

Myotonic Dystrophy types 1 and 2

Answer 12

Type 1: DMPK gene on chromosome 19
– Normal DMPK Expression = Myotonic Dystrophy Protein Kinase(DMPK)
* In muscle, DMPK turns off myosin phosphatase
and allows relaxation of muscle contraction
Type 2: CNBP gene on chromosome 3
– Normal CNBP Expression = Cellular Nucleic Acid Binding Protein (CNBP)
* Found in muscle and heart tissue, exact function is unclear, but thought to be a regulatory protein for other proteins

Question 13

Myotonic Dystrophy “anticipation”

Answer 13

• A parent who already has a CTG or CCTG expansion will pass an already expanded CTG or CCTG sequence to offspring
• As the offsprings cells replicate the expansion is greater and symptoms appear sooner than parents.
• If the offspring passes their expansions along to the next generation,
  then the expansion becomes greater and symptoms appear earlier and so does severity.
• The process continues and families start to see earlier onset and severity so they start to “anticipate” the onset in following generations

Question 14

Myotonic Dystrophy: type 1 presentation

Answer 14

– Congenital form is seen at birth with hypotonia
and inability to breathe or feed, not a good survival
rate
– Adult form: weakness develops later in life
* Mostly seen in facial features and distal limbs
– Ptosis, hollow cheeks, prominent forehead
– Hand muscle weakness
– lower leg, toe, or foot drop
* Sustained contraction of:
– handshake
– calf muscles
– toes

Question 15

Myotonic Dystrophy: Type 2 presentation

Answer 15

– Only seen in Adults
* More mild than Type 1
* Proximal muscles affected (type 1 was more distal muscles)
– Hips and thighs
– Shoulders and upper arms
* Weakness and delayed relaxation of muscles in areas listed
– Trouble climbing stairs
– Difficulty standing
– Difficulty lifting

Question 16

Myotonic Dystrophy diagnosis

Answer 16

– Clinical Presentation
* Age of onset between 20-40 ish
* Family history
– Lab testing - DNA testing to confirm CTG or CCTG repeats

Question 17

Myotonic Dystrophy treatment

Answer 17

– Mexiletine first-line for those pts limited by myotonia (no treatment for
weakness)
* Can potentiate cardiac arrhythmias
– Do not use in pts with 2 nd or 3 rd degree AV block or with
abnormal EKG
– Other meds: Procainamide, phenytoin, quinidine, carbamazepine
– Bracing of effected weak limbs, wheelchairs
– PT, OT, other adjunctive therapies and specialists (eg. Cardiology)

Question 18

Cerebral Palsy =

Answer 18

brain disease causing paralysis
* Cerebral Palsy is an umbrella term for a group of non progressive movement disorders affecting how a person moves.
* Syndrome, not a specific disorder

Question 19

Cerebral Palsy etiology

Answer 19

– Prematurity, Low birth wt - Physical stress and demands on the immature brain is thought to put this population at higher risk
– In utero disorders
– Neonatal encephalopathy
– Kernicterus (bilirubin encephalopathy)
– Perinatal asphyxia, stroke, CNS infections account for 15-20% of
cases
– Multiparity

Question 20

Cerebral Palsy - Pathophysiology

Answer 20

– Injury or abnormal development of the prenatal and neonatal brain can occur at any
time
* depending on stage of development, varied demonstrations of CP can be manifested
* Usually damage from genetic abnormalities, toxic or infectious etiology, or vascular
insufficiency
* Prematurity - physical stress and demands on the immature brain is the main
thought as to why immature infants are at higher risk

Question 21

Location of damage to the brain can dictate what symptoms are demonstrated with cerebral palsy

Answer 21

• Cerebellum – Coordination of movements
• Motor Cortex – Initiation of movements
• Basal Ganglia –Initiation and prevention of movements

Question 22

Cerebral Palsy - etiology

Answer 22

– Hypoxic-ischemic injury
– Structural malformations
– Vascular disorders
– Intraventricular or subarachnoid
hemorrhage
– Intrauterine infections
– Toxins
– Trauma
– Metabolic disorders
– Prematurity (low birth wt)
– Hemolytic diseases
– Maternal hyperthyroidism
– Maternal seizures
– Maternal infection
– Stroke
– Meningitis
– Sepsis
– Third trimester bleeding
– Incompetent cervix
– Maternal use of hormones
– Meconium in amniotic fluid

Question 23

Cerebral Palsy Classifications

Answer 23

– Severity – Gross Motor Function Classification System (GMFCS)
– Body area – Monoplegia, Diplegia, Hemiplegia, Quadriplegia
– Type – Spastic, Dyskinetic, Ataxic, Mixed

Question 24

Gross Motor Function Classification System (GMFCS) for cerebral palsy

Answer 24

– Level 1 - Walks without limitations
– Level 2 - Walks with limitations
– Level 3 - walks using a hand-held mobility device
– Level 4 - Self-mobility with limitations; may use powered mobility
– Level 5 - Transported in a manual wheelchair

Question 25

Spastic movement

Answer 25

Spastic = Stiff or tight muscles
– Hypertonicity is resistant to passive ROM
– Hyperreflexia – increased DTRs
– Voluntary movements are weak and poorly controlled

Question 26

Dyskinetic (Athetoid) movement

Answer 26

Dyskinetic (Athetoid) = involuntary movements
– Chorea – most common
* Random, “dance-like”
– muscle to muscle
– Dystonia
* Random, slow, uncontrolled
– Limbs and trunk
– Can also fluctuate from stiff to Flacid

Question 27

Ataxic movement

Answer 27

Ataxic= shaky or uncoordinated

Question 28

Mixed movement

Answer 28

Mixed= combination of movement disorders
– Spastic and Choreoathetosis (Dyskinetic chorea)
* Motor cortex and basal ganglia
– Athetosis and Ataxia
* Basal ganglia and cerebellum both affected

Question 29

Cerebral Palsy other symptoms

Answer 29

• Pain
  – Muscle cramping
  – Abnormal posture
  – Arthralgias
• Sleep disorders
• Eating
  – Preparing
  – Chewing and swallowing
• Speaking problems
• Vision problems
• Learning disabilities
• Seizures
• Intellectual Delay

Question 30

Cerebral Palsy diagnosis

Answer 30

– Largely clinically based – manifests before 2 years of age
– Physical exam and Hx confirm motor deficit due to cerebral anomaly
* Obtain prenatal, perinatal development history
– Any infections, trauma, unusual circumstances during pregnancy, prematurity…
– Imaging of brain
* If etiology is not previously established
* Cranial ultrasound in premature infant (Looking for periventricular leukomalacia)
* MRI in full-term infant
* CT scan optional but MRI is a better study and has less radiation

Question 31

Physical Exam for movement in cerebral palsy

Answer 31

• Spastic:
  – Push and pull on arms and legs checking
  for spasticity
• Dyskinetic:
  – Fluctuating spastic or flaccid
  – May want to R/O other causes
• Check Reflexes
  – Primitive reflexes that should be lost
  through development
  » Moro, palmar grasp, etc.
  – Sometimes the primitive reflexes will not
  develop at all, or not disappear

Question 32

Cerebral Palsy treatment

Answer 32

multidisciplinary approach
– Goal is for children to develop maximal independence within the limits of their motor and
associated deficits (Merck Manual online)
* Primary Care Provider–Team leader; synthesizes long-term, comprehensive plans and
treatments
* Orthopedist–Focuses on preventing contractures, hip dislocations, and spinal curvatures
* Physical therapist–Develops and implements care plans to improve movement and strength, and
administers formal gait analyses
* Occupational therapist–Develops and implements care plans focused on activities of daily living
* Speech and language pathologist–Develops and implements care plans to optimize the patient’s
capacity for communication
* Social worker–Assists the patient’s family in identifying community assistance programs
* Psychologist–Assists the patient and patient’s family to cope with the stress and demands of the
disability
* Educator–Develops strategies to address cognitive or learning disabilities
– If normal to near normal Intellectual functioning, then children
can go to mainstream classes, compete, and other activities with
accommodations if and as needed
– Speech therapy or other form of communication training