Neuromuscular & Neuromotor Flashcards
Describe the genetic pattern and pathophysiology of DMD
X-linked recessive neuromuscular disorder caused by mutations in the dystrophin gene that result in absent
or insufficient functional dystrophin (a cytoskeletal protein that enables the strength, stability, and functionality of myofibres)
Prevalence of DMD?
15-20/100,000 live male births
What is the cause of mortality in DMD?
Respiratory or cardiovascular compromise
Name 5 red flags for DMD diagnosis
Family history
Delayed walking > 16-18 months
Toe walking <5 years old
Gower’s sign positive
Elevated transaminase (LD, ALT, ALP, CK)
Name 5 motor signs & symptoms of DMD
Name 5 NON-motor signs & symptoms of DMD
What is the genetic cause of DMD? what genetic tests should be ordered?
MLPA (multiplex ligation dependent probe amplification) or comparative genomic hybridization array –> deletion or duplication of DMD gene (70%)
Next generation sequencing –> point mutations, small deletions, small duplications or insertions (25-30%)
If genetic testing is negative, what is the next diagnostic test for DMD? What are the findings that would indicate a DMD diagnosis?
Dystrophin protein testing by immunohistochemistry of tissue cryosections or by western blot of muscle protein extract on muscle biopsy –> absent dystrophin protein
List 8 side effects of glucocorticoids
○ Weight gain
○ Decreased height velocity
○ Delayed puberty
○ Irritability, behavior changes
○ Osteoporosis
○ Increase fracture risk
○ Hirsutism, acne
○ Cataracts, glaucoma
○ Fluid retention/edema
○ GERD
○ Insulin resistance
○ Adrenal insufficiency and crisis
○ Sleep disturbances
○ Cushing features
What is the starting dose of glucocortiocoids (each type) in DMD?
Deflazacort 0.9mg/kg/day
Prednisone 0.75 mg/kg/day
Deflazacort less weight gain
What is the screening guidelines for vertebral fractures in DMD?
Annual DEXA scan. if non-ambulatory increase to q6 months
Lateral xrays for vertebral fracture if pain or decrease in Z score by >0.5 SD
What is the screening guidelines for scoliosis in DMD?
- Ambulatory DMD – clinical monitoring, AP xray spine if clinically identified
- Non-ambulatory – q6-12 months
- When first become non-ambulatory
- 20 refer to orthopedics
List three neurodevelopmental disorders that are associated with DMD?
Increase prevalence of ADHD, ASD, and intellectual disability
Name 3 factors on which you base your decision whether or not to start steroids in a patient with DMD
○ Confirmed DMD diagnosis
○ Immunizations complete
○ Patient can tolerate side effects
○ (Family aware and ok with side effects)
○ (Nutritional assessment complete)
○ (not usually <2 years old, still developing basic skills)
3 strategies to prevent & treat ankle contracture in DMD?
o Ankle stretches 4-6 times per week
o Use of AFOs in standing and rest for passive stretch
o Surgical release of Achilles tendon if <10 dorsiflexion
Exercise guidelines for DMD?
Regular submaximal aerobic activity or exercise, especially cycling or swimming
AVOID - eccentric, high-resistance exercise, overexertion
What is the cardiac monitoring in DMD?
o Echo (<6-7y) or cardiac MRI (>6-7y) and ECG at diagnosis
o Annual cardiac function testing (history & PE) and ECG
o ACEi or ARB onset prior to 10 years old (even if healthy), BB as first line for cardiomyopathy/ventricuilar dysfunction
In DMD, what is the anticipated risk of developing a cognitive impairment
o 20-30% of cognitive difference (ID or specific learning disorder)
Indications for increase frequency of respiratory evaluation in DMD?
o Ambulatory to non-ambulatory
o Clinical history of sleep disordered breathing (fatigue, dyspnea, morning headaches, frequent nocturnal awakenings, difficulty concentrating, frequent nightmares)
o Deteriorating FVC
o If on assisted ventilation pCO2 >45 or SPO2 <95% need for daytime ventilation
Name 2 causes of false negative and 2 causes of false positive results of DMD testing on newborn screen
- False negative - storage at higher than room temperature and humidity, storage > 7 years, low birth weight or prematurity
- False positives - other muscular dystrophies (Becker’s. congenital muscular dystrophies, limb-girdle muscular dystrophies); CK-MM may also be elevated in unaffected newborns due to muscle trauma during birth (reduce over time rather than increase)
Name 2 DSM-5 Diagnoses seen in people with myotonic dystrophy
ADHD
Intellectual disability (50%, FSIQ 50-70)
Anxiety
Name 3 specific cognitive-processing deficits in myotonic dystrophy
o Memory impairment
o Executive dysfunction
o Visuospatial processing differences
What is the test for myotonic dystrophy
PCR for tandem repeat expansion in DMPK gene, chromosome 19q13.3.3 >50 CTG repeat
Other:
EMG – characteristic myotonic discharges with bursts of repetitive potentials
Muscle Biopsy – grossly abnormal muscle fibre size, fibrosis
CK – normal to mildly elevated
Low level of IgG
Liver function abnormalities – up to 50%
MRI – cerebellar atrophy
Name 3 features that differentiate Becker’s muscluar dystrophy from DMD
Older age of onset 5+ (BMD) vs 2-3 years old DMD
Ambulatory longer
CK 5x ULN vs 10-20x ULN in DMD
Genetic testing for Becker’s muscular dystrophy
- Multiplex ligation-dependent probe amplication (MLPA)
- Comparative genomic hybridization array
70%
25-30% will require sequencing for point mutations
if still no diagnosis then muscle biopsy - reduced dystrophin protein (vs absent in DMD)
Name the genetic cause of Friedreich Ataxia
Mutation in FXN gene with >66 GAA repeats, chromosome 9
Disrupts frataxin protein production
Describe the genetic problem in SMA
Homozygous deletion of SMN1 exon on chromosome 5 (autosomal recessive)
SMN2 number of copies associated with clinic phenotype
4 clinical features of SMA
Fasciculations
Proximal muscle weakness
Progressive
Decreased or absent reflexes
Sensation is preserved
Risk in congenital myopathy during anesthesia
Malignant hyperthermia
Biopsy finding in nemaline rod myopathy
Rod-like structures in predominance and type 1 fibers
4 interventions to support adequate nutrition and safe feeding in child with muscular dystrophy
SLP assessment
Thickened feeds
Nutritional supplementations
Tube feeds
Name of 3 FDA approved medications to treat SMA
Zulgensma
Nusinersen/Spinraza
Risdiplam
What percentage of BMD is expected to be identified on MLPA genetic testing for deletion/duplication
85%
Benefits of steroids in DMD?
Prolonged ambulation
Preserved upper limb function
preserved respiratory function
Avoid scoliosis surgery
If side effects or reduced tolerability of steroids in DMD what are the next steps?
Reduce steroids by 25-30% and reassess in 1 month
How often do you screen female carriers with DMD for cardiomyopathy
every 3-5 years with ECG and echo starting in early adulthood for cardiomyopathy
What is the neurodevelopmental profile for DMD?
2 predictors of poor outcome/mortality in CP
gmfcs > III (ie IV or V)
feeding difficulties (aspiration risk)
GMFCS is based on what level of child’s abilities
typical performance
name 3 tests to assess function in CP
Gross motor functional measure (GMFM)
6 min walk test
Canadian Occupational Perfomance Measure (COPM)
name 5 comorbidities of DCD and the two most common (first)
1) ADHD
2) speech and language impairment
3) Anxiety
4) ASD
5) SLD
4 medication categories that treat tics and 1 example of each
-alpha 2 agonist - clonidine
-atypical antipsychotic - risperidone (or typical haloperidol)
-anti-epilecptic - topiramate
-SSRI - fluoxetine
4 reasons for GTube in CP?
history of aspiration
prolonged feeding time
malnutrition/malabsorption
significant weight loss
refractory GERD
Family/social factors
Name the components of the ICF fraemwork of disability
5 key components that distinguish spasticity from dystonia and what you would find for spasticity or dystonia.
6 hyperkinetic disorders (types of hyperkinesis) of childhood
Dystonia
Tics
Stereotypies
Tremor
Myoclonus
Chorea
4 characteristics of movement disorders to evaluate (to differentiate types)
Rhythmic
Involves repeated postures
involves stereotypes movements
is suppressible
