Neuromuscular Flashcards
What is the inheritance pattern of DMD and BMD?
X-linked
What is the gene location associated with DMD and BMD?
Xp21
When is ambulation lost in DMD without steroids? When is it lost with use of steroids?
Without: 7-13
With 9 -15
What type of mutation occurs in DMD?
Frameshift causing a premature stop codon creating a nonfunctional protein
What type of mutation occurs in BMD?
In frame mutation that produces a small but somewhat functional protein
What is dystrophin?
A cytoplasmic protein inside the sarcolemma that anchors the muscle cell to the extracellular matrix
What happens to a muscle fiber that lacks dystrophin?
Repeated contractions trigger degeneration and a inflammatory cascade
Where is dystrophin located (5 locations)?
Skeletal muscle, smooth muscle, cardiac muscle, cardiac purkinje cells, brain tissue
At what age range does DMD usually present?
2 - 6
What is standard of care for the diagnosis of DMD?
Complete genetic sequencing
What type of mutations cannot be detected by complete genetic sequencing?
Intronic mutations (2%)
At what age should DMD patients start getting cardiac MRIs
6
How often should cardiac MRIs be done in DMD patients?
Every 1-2 years from 6 to 10 and yearly after that
What are the first two pulmonary parameters to show impairment in the DMD population?
Maximal inspiration and expiratory pressures
What percentage decline occurs in the percentage predicted FVC from 10 - 18 in the DMD population?
5 to 6%
When should DMD patients start daily use of a cough assist (in-exsufflator) machine?
When FVC%p approaches 60%
When should DMD patients be considered for nocturnal BiPAP?
When FVC%p approaches 50%
What does a FVC of less than 1 L in a DMD patient indicate?
5-year survival of less than 8%
At what stage is BiPaP usually started in DMD patients?
Early nonambulatory
Why is oxygen usually contraindicated in DMD?
Because the pulmonary impairment is usually restrictive and oxygen may lower respiratory drive
What type of dysfunction causes difficulty swallowing solids?
Esophageal
What type of dysfunction causes difficulty swallowing liquids?
Oropharyngeal
What are two common endocrine features of DMD?
Delayed puberty, linear growth impairment
What are 4 indications for referral to endocrinology in the DMD population?
Growth of less than 4cm per year, absence of pubertal development by age 14, loss of ambulation, bone fracture
How should bone health be monitored in DMD patients?
Lateral spine x-ray every 2 (on steroids) to 3 years (steroid naive)
Where in the brain is dystrophin expressed in particular
The hippocampus
What is the mechanism of glucocorticoids modifying progression of DMD?
They improve dystrophin expression by decreasing expression of microRNAs
What is the mechanism of Eteplirsen in treating DMD?
It causes skipping of exon 51
When is spine surgery considered in DMD?
Early (curve 20 degrees or more)
In DMD, which limb girdle weakness presents first?
pelvic girdle precedes shoulder weakness by several years
What is the average age for WC dependence in DMD?
10
When does scoliosis present in DMD?
Around 12- 15 years old or after 3 - 4 years in the wheelchair
What FVC level is a contraindication to spinal surgery due to risk of morbidity?
FVC < 40%
Which facial muscles are usually spared in facioscapulohumeral MD?
masseter, temporalis, extraocular, and pharyngeal
Which muscle disease typically presents in adolescence with elbow flexion contractures?
Emery-Dreifuss MD
In which muscular dystrophy are cardiac complications rare?
Facioscapulohumeral
Which congenital myopathy presents with a predominance of type I fibers and a high incidence of malignant hyperthermia?
central core myopathy
Which type of muscular dystrophy presents with distal greater than proximal weakness?
myotonic MD
What lab can help differentiate if AST and ALT elevations are muscular or hepatic in origin?
GGT because it is not in muscle
What mobility function is typically lost first in DMD?
ability to stand from the floor
What is predictive of loss of ambulation in 4 years in the DMD population?
a decline of 10% in the 10-meter run/walk over the course of a year
What is the average age of full time WC use in a non-treated DMD patient?
10 years old
Past what age are patients with BMD typically able to ambulate?
16
What is the median age of survival in DMD?
25 years old
What is the median age of survival in BMD?
67
What are three benefits of steroid treatment in DMD?
prolong ambulation by about 3 years, preserve upper limb and respiratory function, decrease need for scoliosis surgery
What should be given before starting steroid therapy in a DMD patient?
live-virus vaccines
What steroid side-effects should boys with DMD be monitored for?
cataracts, HTN, DM, weight gain, osteoporosis, growth retardation
What pattern of inheritance of LGMD presents in childhood?
recessive
What are two extramuscular features of early-onset FSHD?
retinal vasculopathy and hearing loss
What is the genetic abnormality seen in myotonic dystrophy type 1?
trinucleotide repeat of CTG
What is the inheritance pattern of almost all cases of Myotonic Dystropy Type 1?
autosomal dominant maternal inheritance
What muscles are typically week in myotonic dystrophy type 1?
facial muscles, finger flexors, and ankle dorsiflexors
Where do contractures typically occur in Emery-Dreifuss MD?
neck, elbows, and ankles
What prophylactic treatment should patients with Emery-Dreifuss MD undergo? Why?
pacemaker/defibrillator placement due to progressive cardiac disease with propensity for arrhythmia
What is the inheritance pattern of congenital muscular dystrophies?
autosomal recessive
What two things are highly variable in congenital muscular dystrophies?
degree of muscular involvement and clinical course
What type of CMD presents with diffuse brain MRI white matter abnormalities?
Merosin deficient
What is the most severe form of collagen VI deficient CMD with ambulation lost by second decade due to contractures and weakness?
Ullrich CMD
What is the most mild form of collagen VI deficient CMD with ambulation maintained into adulthood?
Bethlem CMD
What skin finding can be seen in all forms of collagen VI deficient CMD?
hyperkeratosis pilaris (goose bumps)
What presents with early onset muscle weakness and hypotonia that is static or improving over time?
congenital myopathies
Can CK and EMG findings be normal in congenital myopathies?
yes
What presents with progressive ophthalmoparesis, ataxia, and proximal myopathy?
Kearns-Sayre Syndrome
What presents with exercise induced cramps and myalgia during childhood?
myophosphorylase deficiency (McArdle’s disease)
When do limb contractures typically present in the pediatric patient with myopathy?
after transition to full-time WC use
What type of cast can be used to treat elbow or knee flexion contractures?
dropout knee extension serial cast
Why is heel cord lengthening rarely needed in a muscular dystrophy patient?
the calcaneus is usually already in dorsiflexion
What can cause immediate loss of walking in a DMD patient with quads less than 4/5 strength?
achilles tendon lengthening
When should a DMD patient be referred to Orthopedics for spinal monitoring?
curve over 20 degrees
What are two types of heart block seen in myotonic dystrophy?
1st degree AV, bundle branch
What is one advantage of a scooter over a standard WC?
they are easier to transfer to and from due to elevated seat height
What type of muscle contraction is eliminated in the water?
eccentric
What is the most common heritable peripheral neuropathy?
HMSN (CMT)
What is the inheritance and pathology of CMT1
AD and demyelinating
What are the earliest abnormalities seen on exam in CMT1?
vibratory, touch, and pain sensation
Which type of CMT is characterized by severe childhood-onset weakness and sensory changes?
CMT4
What is the genetic abnormality with CMT1A?
duplication of PMP-22
What is the genetic abnormality with hereditary neuropathy with pressure palsy?
deletion of PMP-22
What is spared in hereditary sensory and autonomic neuropathy 1
vibratory sensation
What has been shown to attenuate progression of distal weakness in children with CMT1?
progressive long-term resistance strength training
What sleep disorders are seen in CMT in a higher incidence than the general population?
restless leg syndrome, sleep apnea
What factor determines the severity of SMA?
The number of copies of the SMN2 gene
When does SMA1 present ?
Many do not show signs until after 2-3 months. Patients will present within 4 months of life.
What has traditionally be the life expectancy in SMA1
2 years old
When does SMA2 present?
7 to 18 months old
What is another name for SMA1?
Werdnig-Hoffman disease
What is another name for SMA2?
Dubowitz disease
What is another name for SMA3?
Kugelberg-Welander disease
What muscles are typically spared in SMA?
diaphragm, facial and extraocular muscles
When does SMA3a present?
after 18 months
When does SMA3b present?
after 3 years old
How may copies of SMN2 does a SMA1 patient have?
2
How many copies of SMN2 does a SMA3b patient have?
4
How many copies of SMN2 does a SMA2 or SMA3a patient have?
3-4
By when do the majority of SMA3a patients lose the ability to ambulate?
20 years old
What is the major functional difference between SMA1 and SMARD?
In SMARD, there is diaphragmatic weakness with early ventilator dependence
What is the mechanism of Nusinersen?
modifies pre-mRNA splicing of the SMN2 gene allowing inclusion of exon 7 and expression of a full-length SMN protein
What is the advantage of Risdiplam over Nusinersen?
Risdaplam can be given orally
What is the mechanism of Onasemnogene?
delivery of a SMN1 gene via a AAV9 vector
Are eccentric exercises safe in mild SMA?
yes
What is best practice for scoliosis monitoring in SMA?
XR every 6 months for curves over 20 degrees
What kind of neuropathy is seen with Vincristine?
axonal motor and sensory neuropathy
What kind of neuropathy is seen with Cisplatinum?
axonal sensory neuropathy
What is the prognosis for neuropathy caused by cancer treatments?
recovery should occur after discontinuation of treatment but it may be incomplete and protracted
What self-resolving symptoms can be seen with Oxaliplatin infusion?
dysphagia, dyspnea, and perioral paresthesisas
What kind of neuropathy is seen with lead exposure?
Axonal sensory-motor neuropathy (classically more motor affecting the hands)
What presents with muscle fatigue and eyelid ptosis?
congenital myasthenic syndromes
Antibodies to which 2 receptors are seen in juvenile myasthenia gravis?
MusK and LRP4 (leucine rich protein 4)
What symptom is most frequently noted in juvenile myasthenia graves (JMG)?
ptosis
When does infantile botulism typically present?
2 weeks to 6 months of age
What should be suspected in a 1 month old baby with acute onset of hypotonia, weakness, and respiratory insufficiency?
infantile botulism
What is the most common finding on examination of a child with acquired botulism?
cranial nerve involvement
What finding is most predictive of respiratory compromise requiring ventilation in a patient with GBS?
severe involvement of the upper extremities
What is seen in CSF of GBS patients?
increased CSF protein and low cell count
What anti-body is associated with Miller Fischer syndrome?
anti-GQ1b
What are two predictors of long-term muscle weakness in children with GBS?
age less than 9, rapid progression to weakness within 10 days of onset
What are two features seen in Miller Fischer syndrome?
ataxia and ophthalmoplegia
What are 3 benefits to using steroids in the DMD population?
prolong ambulation by 2-3 years, preserve respiratory function, and decrease the need for scoliosis surgery
How does prognosis for motor recovery in GBS differ between children and adults?
Children generally have a better prognosis for motor recovery than adults
What medications can trigger a myasthenic crisis?
botulinum toxin, Mg, antiboitics, anticonvulsant, psych meds, beta-blockers/CCBss
