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
Name 2 reasons why BMI is not a good indicator of nutritional status in CP and 2 alternatives
-differences in body composition
-measurement error/difficulty
-tricep skinfold measurements with appropriate modified equations (for CP)
-mid arm circumference
-technology based body composition tools
4 reasons for GTube in CP?
history of aspiration
prolonged feeding time
malnutrition/malabsorption
significant weight loss
refractory GERD
Family/social factors
Child iwth CP, vp shunt, on baclofen + carbomazipine, abdo pain + increased spasticity
- 5x labs
- 2x Ix
- CBC
- CRP
- Renal function, lytes
- blood culture
- carbomazipine level
Abdominal ultrasound
VP shunt series (CT or MRI fast)
Differences between tics and stereotypies
Tics
- discrete, sudden, non-rhythmic often involving the head and neck and may have premonitory urge
Stereotypies
- rhythmic, purposeless, patterned, episodic, and repetitive
- often onset younger age
Differences between GMFCS I and II
May require support for transfers and on stairs
May require walker for long distances/endurance
-DIfficulty jumping or running
4 specific diagnosis that may benefit form power mobility in preschool
1) SMA I or II
2) CP >/= III
3) Spina bifida
4) congenital myopathy
12 years old boy with toe-walking, ankle flexion contractures, ck 6 times upper limit of normal, sore muscles, quadriceps muscle weakness bilaterally. Most likely diagnosis? Initial test to confirm this diagnosis?
Becker’s muscular dystrophy
Dystrophin gene anlaysis (MLPA)
5 symptoms of malnutrition on history or physical other than growth parameters
2’ amenorrhea
history of fractures
Muscle waisting
Lanugo
Pallor
Ulcers
Angular chelitis
4 components of CP diagnosis definition
Insult to the developing brain
Non-progressive
Leading to impairments in movement, posture and activity limitation
Accompanied by effects on cognition, perception, sensation, communication, and behavior
Side effects of levodopa (4)
dizziness
headaches
dyskinesia
orthostatic hypotension
rhabdomyolysis
hallucinations
4 features of Idiopathic toe walking
Onset at the time of walking (12-18 months)
Symmetric
No associated hypertonia, hyperreflexia or clonus
Normal sensation and strength
Non progressive
Name the components of the ICF fraemwork of disability
4 benefits of orthotics
- prevention of contracture or foot deformity
- gait stability
- gait endurance and efficiency (appropriate heel contact)
- Passive stretch and prevention of overstretch
Name 3 interventions for kids with cortical visual impairment
bright contrasting colours
reduced visual stimulation
objects with sound or movement as well
name 5 medical contributors other than sleep hygiene for child with poor sleep
Pain
GI symptoms
Seizures
Sleep associations
Parasomnias
Snoring/OSA features
13yo girl with hempiplegic CP. Have assessed for spasticity and dystonia. What 5 other aspects of body function in the ICF would you look for on exam that would explain her difficulties with bimanual function?
Contractures
Fractures
Pain
Seizures
Vision impairment
Voluntary muscle control
grip strength
active versus passive range of motion
Describe the two maneuvers completed on the HAT to assess for spasticity.
. Velocity dependent resistance to stretch
. Presence of a spastic catch
5 key components that distinguish spasticity from dystonia and what you would find for spasticity or dystonia.
Parents are adopting a child who was shaken when she was an 8-week-old. Her presenting GCS was 4. She spent two weeks ventilated in the ICU. She is now 1-year-old. She crawls and pulls to stand. She has no words. Her motor exam and tone are normal. She is happy. She has no hearing or visual concerns. What two things would you counsel her potential adoptive parents about?
- Lowered verbal IQ, performance IQ, and full-scale IQ
- Behaviour problems (e.g., hyperactivity, conduct problems, poor self-control, and internalizing difficulties)
what are the four indications for starting dystonia management according to the AACPDM pathway?
- Dystonia causing pain
- Dystonia affecting sleep
- Dystonia interfering with positioning
- Dystonia impeding function
- Status dystonicus (or “periodic status dystonicus”)
Three reasons you would refer to an orthopedic surgeon based on the AACPDM pathway for hip surveillance?
- Positive response to question regarding pain
- Pain on physical examination
- Migration percentage > 30% on AP pelvis
- Hip abduction passive range of motion < 30 degrees
3.5yo boy, GMFCS II. Describe his abilities in sitting, movement in and out of sitting, standing, crawling and walking.
Sitting with hand support
get in and out of sitting without assistance
prefers to cruise when walking
stands with support
4-point crawl
Name 3 patient characteristics known to be associated with life expectancy in cerebral palsy
more severe limitations in motor abilities (i.e. higher GMFCS)
more severe limitation in feeding abilities
more severe cognitive impairment
more severe visual disabilities
seizures
5 requirements of normal gait
· Stability in stance
· Clearance of foot in swing
· Pre positioning of foot
· Energy conservation
adequate step length
4 aspects about the unique anatomy of young children that make them more susceptible to brain injury.
· Relative macrocephaly (large heads to small neck ratio)
· Weak neck muscles
· Elastic blood vessels
Incomplete myelination
4 physical exam maneuvers to assess hypotonia in the child and most common cause of newborn hypotonia
pull to sit
vertical suspension
horizontal suspension
scarf sign (upper limb adduction across the trunk)
Think -HINE
What to advise re genetic testing in CP?
1.) Genetic studies are not routine in CP as our understanding of the role of genetics in CP is still limited. It could be considered for reasons of closure, family planning, but very rarely informs treatment options or atypical features of CP
2.) I would recommend genetic testing specifically if there was a family history of CP, recurrent miscarriages, neurodegenerative disease, or an atypical presentation that made me suspicious of an alternative diagnosis (ex. normal MRI, metabolic history, migration abnormalities on MRI)
What is the single best predictor of developmental outcome in a child with myeolomeningocele
high level of lesion (into the thoracic region)
3 developmental conditions/learning impairments in addition to ID in a child with agenesis of the corpus collosum
Language impairment
Attention-deficit/hyperactivity disorder
Gross/fine motor delay
Benefits of SDR ?
Improvements in lower limb spasticity
· Increase in the range of movement at the lower limb joints (impairment dimension) and either no change or improvement in lower limb strength
· Moderate degree of certainty that these improvements in the impairment dimension are maintained up to 5 years after SDR and some weaker evidence that the improvements are maintained in the even longer term
· In ambulatory patients, improved range of movement in the lower limbs during walking and increased stride length after SDR and moderate evidence for increased gait velocity
· Evidence that there is an increased GMFM after SDR
· Improvements in self-care and performance of activities of daily living after SDR
definition of CP
A group of disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, cognition, communication, perception, and/or behaviour, and/or by a seizure disorder.
3 ways to decrease risk of osteopenia in CP
Nutritonal counseling & dietary recommendations (calcium intake)
Supplemental Vitamin D - 800-1000 IU daily
Weight bearing
6 items of DDx for idiopathic toe walking
a) tethered spinal cord
b) ASD
c) cerebral palsy
d) neuromuscular disorder (Spinal Muscular Atrophy)
e) Muscular Dystrophy (Duchenne, Becker)
f) Peripheral neuropathy (Charcot Marie tooth)
g) Equinovarus foot deformity
h) Congenital achilles contracture
5-year-old with GMFCS III what can this child do that GMFCS IV can’t, list 3 things
a) Sit on a regular chair
b) Move in and out of chair independently using a surface to push or pull on
c) Climb stairs with assistance
d) Use a hand held mobility device on level surfaces
Child with GMFCS IV parents want to know if they’ll walk by 18 years old, 3 things to counsel on
a) A child classified as GMFCS IV would not be expected to walk
b) GMFCS is a valid predictor of motor function and does not change over time
c) Important to plan rehabilitation with the GMFCS level in mind
What are the 4 best predictors of mobility in a child with spina bifida?
history of shunting for significant hydrocephalus
spine level of lesion
history of surgical release of hip or knee contractures
-cognitive abilities
-access to resources
5 features of MSK exam in idiopathic tone walking
Toddler
Symmetrical exam
Can bring heels to floor
Normal strength - no weakness
Normal reflexes - absence of increased reflexes
Normal tone - no hypertonia
Normal sensation
Well coordinated gait pattern
Older Children
May have decreased ROM (dorsiflexion)
May have contractures
Gastroc, soleus and achilles tightness
24 month old with SMA type 2. What MSK complications do you need to watch out for to ensure she can be independent in her mobility
Scoliosis
Contractures
Hip dislocation
Fragility fractures
Muscle Weakness
What is the international consensus on the minimum age to use power mobility in a child with normal cognitive function, vision etc.
12- 18 months
Contraindications to botox? Name 5
-significant swallowing concerns / risk of aspiration
-allergic reaction
-excess weakness
-generalized tone/too many target muscles
-severe fixed contractures
-bony torsion and joint instability
-bleeding disorders
Neuromuscular conditions
Active bladder infxn and urinary incontinence (or urinary incontinence actively being treated and UNABLE TO VOID)
Injection site infxn
Poor respiratory reserve
Allergy
3 reasons GMFCS should NOT be used in populations other than CP?
Not been validated in populations other than CP
Not reliable for conditions other than CP
Not developed to be an outcome measure
what is Tardieu scale used for? What does it measure?
Used for:
-Quantify spasticity
-identify contractures
Measures: Spasticity
CP GMFCS II what would you discuss regarding sexuality
Fertility / contraception
Safe sex (identity, consent, condoms, STI prevention)
Support with sexual function (ejaculation, erection)
Vaccines, HIV prevention
Positioning and comfort
describe GMFCS IV abilities in seated, transfers & standing, walking, wheelchair needs
-adapted seating, transfer and standing with 1-2 people (but may support weight with legs), walking with body support walker, conventional WC pushed by someone else, might be able to operate motorized WC
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
4 characteristics that differentiate tics from stereotypies
Rhythmic (stereotypies) vs nonrhythmic (tics)
Preceding urge/thought (tics) vs no preceding urge/thought (stereotypies)
Continual (stereotypies) vs discrete (tics)
Change in location/type (tics) vs no change in location/type (stereotypies)
5 components of constipation management
diet, hydration, exercise
education
bowe routines
clean out
maintenance therapy
8 areas to assess for on history in a child with GMFCS III who has nutritional concerns
Weight changes
Developmental skills related to feeding
Equipment use
Feeding time
Respiratory distress with feeds
GERD symptoms
Stress at mealtimes
Dietary restrictions or food refusal
4 side effects specific to levodopa carbidopa
nausea/vomiting
Dyskinesia
Orthostatic hypotension
peripheral neuropathy
impulse control disorder
behavioral concerns
Withdrawal
Somnolence
indication for serial casting in idiopathic toe walking in
-10 to 10 degree dorsiflexion
3 physical features you can ask about on hx or see on physical that indicate nutritional compromise (aside from growth measurements)
fractures
pallor
decreased subcutaneous tissue
menstration changes
2 alternatives to BMI to assess the nutritional status of a patient with CP
DEXA scan
skinfold measurements
4 reasons for Gtube in GMFCS IV
Feeding efficiency if prolonged feeding
Frequent aspiration
FTT or nutritional deficiency
Respiratory distress while feeding
GErD
Dysmotility
4 medications for treatment of chronic functional constipation
Senna
Bisacodyl
Lactulose
PEG3350
3 treatments for nocturnal enuresis
Alarm system
DDAVP
Imipramine
(NOT behavior therapy)
4 signs of organic cause for encopresis
lower imb weakness
decreased lower limb tone
hyporeflexia, areflexia
reduce anal tone
lack of anal wink
meds for clean-out
constipation
PEG3350
Enema
lactulose
glycerin suppository
Risk factors for iron deficiency in GDD and investigations
Restrictive diet
High milk intake
prematurity
Low SES
Exclusive breast feeding > 6 months
Lead exposure
low dietary intake of iron rich foods
CBC
ferritin
iron studies
factors in treating encopresis
education
bowel routine
disimpaction
maintenance therapy
dietary modification
Side effects of B-complex vitamins
thrombosis
pruritis
diarrhea
anaphylaxis
Acne
abdominal pain
headache
paresthesia
You are seeing a 10 year old boy with a previous diagnosis spastic diplegic CP for assessment. Name 5 features on examination and/or history that would make you concerned for a diagnosis of hereditary spastic paraplegia?
Family history fo CP or neuromotor disorders
Bladder dysfunction
Pes cavus or hammer toes
Impaired vibration sense in the elgs
progressive symptoms
3 most common causes of pain in CP?
dystonia
constipation
hip disclocation
List 5 pain behaviors seen in children with severe neurologic impairments
Vocalizations
Facial expression
consolability
interactions
sleep changes
movement
tone
physiologic - tachycardia, sweating
atypical features - laughter, breath holding, slef injury
5 medications for pain with severe NDD
gabapentin
amitriptyline
clonidine
morphine
methadone
