Neurodegenerative Diseases Flashcards
disorders with primary pathology affecting any part of the motor unit from the anterior horn cell out to the muscle
neuromuscular disease
a group of muscle diseases that are genetic in nature
muscular dystrophy - type of neuromuscular disease
steady, progressive degenerative course
neuromuscular diseases
how to classify neuromuscular diseases
- microscopic evaluation of muscle tissue as well as clinical presentation (distribution of weakness, mode of inheritance, pathologic findings)
a group of proteins that link sub-sarcolemmal cytoskeleton and extracellular matrix with the contractile apparatus of the muscle cell membrane
dystrophin-glycoprotein complex (DGC)
what is the gene for duchenne muscular dystrophy (DMD)
dystrophin-glycoprotein complex (DGC)
what are duchenne muscular dystrophy (DMD) and becker muscular dystrophy (BMD)
dystrophinopathies
in DMD, dystrophin is
absent
in BMD, dystrophin is
deficient
limb girdle muscular dystrophy (LGMD) are known as _____, and sarcoglycan proteins are
- sarcoglycanopathies
- deficient
another name for duchenne muscular dystrophy
pseudohypertrophic muscular dystrophy
progressive MD; Dystrophinopathy in which children become weaker and eventually die due to respiratory failure
DMD
what is DMD linked to
x-linked inheritance pattern - M get disease from mom
how to confirm DMD
lab studies and muscle biopsies
what is abnormally high in DMD
serum creatine kinase (CK)
findings in muscle biopsy for DMD
- degenerating and regenerating fibers
- inflammatory infiltrates
- increased connective tissues and adipose cells
- immunohistologic staining - absence of dystrophin
absence of dystrophin in DMD leads to disruption of linkage between
cytoskeleton and extracellular matrix
lack of dystrophin leads to
sarcolemmal instability and increase in susceptibility of microtears
what exacerbates microtears in DMD
muscle cx
when is onset of DMD
2-3 y/o
sx of DMD
reluctance to walk, falling, difficulty getting off floor, toe walking
what age can a child with DMD typically ambulate to
9-10 y/o or more with steroids
pseudo-hypertrophy of weak muscles common in
DMD - calf muscles
does weakness progress with DMD
yes
what muscles typically become weak earliest in DMD
proximal muscles
what causes exaggerated lumbar lordosis in DMD
weak hip and knee extensors
_____ is a compensation by the child to attempt to align the center of gravity anterior to the fulcrum of the knee joint and posterior to the fulcrum of the hip joint in DMD
lordosis
describe BOS, gait pattern and other key characteristics of DMD
- wide BOS
- ER/toe out
- waddling gait pattern
- ITB contractures
- gower’s sign
contractures with DMD progression
- typically PF, inversion
- hip flexion
- knee flexion (in WC)
- elbows, shoulders, long finger flexors
DMD most kids are able to walk, climb stairs, and stand up from floor until what age and then will see rapid decline in function
6-7
when is loss of unassisted ambulatory function seen in kids with DMD
9-10
any kid who remains ambulatory after age 13 is considered to have
BMD or an intermediate phenotype
used to assess function
functional ability grading system (UE and LE)
mildest of x-linked progressive dystrophies
BMD
ambulation till what age with BMD
16 or slightly beyond
slower breakdown of muscle than DMD –> some dystrophin produced
BMD
when is BMD present
5-15
what is intermediate MD
loss of ambulation between 13-16th birthday
life expectancy of BMD
40
body structures impaired with BMD
- scoliosis
- respiratory involvement
- GI system
- cardiac
- cognition
what is often the cause of death in BMD
respiratory involvement –> nocturnal hypoventilation
interventions for MD
- flexibility
- stretching
- bracing/night splints
- serial casting
- prolong functional capacity
- no aggressive strengthening
- NO ECCENTRICS
- sub max endurance training (no post exercise soreness, pool or bike, concentric exercises)
- assistive technology
- adaptive equipment
autosomal dominant disorder to chromosome 19
myotonic dystrophy
sx typically seen during adolescents with myotonia (delay in muscle relaxation time, muscle weakness)
myotonic dystrophy (DM1)
c/o of myotonic dystrophy
weakness and stiffness
characteristics of myotonic dystrophy
- a characteristic long thin face with temporal and masseter muscle wasting, frontal balding, wasting of SCM
- Distal wasting and weakness, foot drop, difficulty opening jars
Progressive muscular dystrophies that affect proximal musculature
LGMD
onset of LGMD
variable, child to adulthood
Interneuron abnormality and loss of anterior horn cells
SMA
what are the 3 types of SMA based on
maximal ability of child
child never learned to sit
SMA type I
child learns to sit but never learns to walk w/o AD
SMA type II
child walks independently
SMA type III
SMA genetics
- Autosomal recessive inheritance pattern
- Gene defect on 5q13
- Both copies of SMN1 gene in each cell have mutations
- Survival motor neuron (SMN) is located here
SMA
survival motor neurons
associated with diminished levels of SMN and loss of motor neurons
SMA
EMG shows diminished action potentials
SMA
muscle biopsies show small atrophic fibers interspersed with groups of large hypertrophic fibers
SMA
are the lack of innervation to the motor unit
atrophic fibers
all kids with SMA have
absent DTRs, sensation intact as is cognition
Werdnig-Hoffman Disease
SMA type I
noted in first 3 months of life, decreased movements in womb, axial hypotonicity, difficulty feeding
SMA Type I
head lag pull to sit, drape over hand in landau, legs in abd/flex (froglegged), arms move with elbows on support surface
SMA type I
cannot maintain head in midline, limited ability to take food by mouth, limited respiratory function, paradoxical pattern of breathing, pulmonary infections
SMA type I
survival age SMA type I
less than 2 years without aggressive pulmonary management
when does SMA Type II present by
Presents later in 1st year of life
Can sit but cannot pull to stand
Proximal weakness, wasting of extremities and trunk musculature
Fasciculations of tongue common
Resting tremors
Delay in acquisition of gross motor skills
SMA type II
Prone and quadruped most difficult due to inability to control head
Contracture formation at knee flex, PF, elbow flexors and wrist flexors
Pts might walk but not independently, use bracing or AD
Ambulation not usually functional for short distances
KAFOs for standign programs
SMA type II
75% of SMA type II can sit until ____ and 50% can sit until ___
7
14
survival SMA type II
into adulthood but susceptible to pulmonary infections
Kugleberg-welander disease
SMA III
Progressive weakness, absent reflexes, fasciculations
SMA type III
presentation onset SMA type iii, what age correlated to poorer outcomes
- toddlers to adulthood (adulthood = type IV)
- < 2 onset = poor
SMA interventions/tx
Develop sequencing/facilitation/handling
Strengthening!!
ROM/splinting
positioning/adaptive equipment (wedges/towel rolls, slings/springs, switch toys)
Power mobility (18mo - 2 y/o)
Bath equipment
why can you strength with SMA
bc due to lack of innervation, NOT muscle destruction
hereditary motor and sensory neuropathy; caused by mutations in genes that produce proteins responsible for structure/function of peripheral N axon or myelin sheath
charcot-marie-tooth (CMT) disease
nerves slowly degenerate, resulting in muscle weakness and atrophy, and reduced ability to feel heat, cold and pain
charcot-marie-tooth (CMT) disease
typical features charcot-marie-tooth (CMT) disease
foot drop (hallmark); high stepped gait; high arches; hammertoes; later onset of muscle atrophy in hands (fine motor deficits); onset of sx is adolescents or early adulthood; progression gradual; typical life expectancy
