lec 4 Flashcards
(37 cards)
What is neuromuscular disease
- Damage to the muscle or nerves that turn on muscles
(motoneurons) - Motor unit is the alpha motoneuron and ALL the muscles cells
that it connects to - So damage could be to nerve (motoneuron) or the muscle
motorneuron disease?
amyotrophic lateral sclerosis
neuromuscular junction disease
myesthenia gravis
muscle disease
muscular dystrophy
upper motor nueron
cell body of neuron located in the cortex (M1,
premotor, S1) and axon is travels via the CST and synapses on the lower
motor neuron
lower motor neuron
(alpha motoneurons ) - cell body of neuron
located in the spinal cord or brainstem and sends out axon that directly
innervates skeletal muscle fibers
- cranial nerves also have alpha motor nuerons, that go to control speech, eyes, (brainstem also has motor alpha motor nuerons)
ALS
- Combination, damage to both upper and lower
what symptom is in all 3
-weakness, difficulty turning on muscles
Motor Nueron disease variance
Motor neuron diseases are a group of progressive neurological
disorders that destroy motor neurons
* Examples:
Amyotrophic Lateral Sclerosis (ALS)
Primary Lateral Sclerosis (PLS)
Progressive muscular atrophy
Post-polio syndrome
ALS
- less common than other diseases
- far more progressive, and degenerative
- speed really fast
common in older men - when occurs early dont progress as fast
- Lou Gherics disease 5 years to death on average, Stephen Hawking got it young his progressed slowly 40 years
- average typical pace but it can be very diff
- Stephen Hawking, has nothing to do with cognition, only motor
- progressive, pace is diff
causes of ALS
- not really clear cause
- environmental? maybe hereditary
-pathophysiology not clear, theory about glutamate toxicity
-Survival: - 80% of people with ALS die within 2-5 years
- Only 5% live >20 years
- Stephen Hawking lived over 50 years with the disease
- Some cases relate to Genetics:
- Familial accounts for approximately 10%
- 1/3 have defect in a gene of unknown function (C9orf72)
- 20% of this 10% have defect in Superoxide dismutase 1 (SOD1) gene
- SOD1 enzyme is a powerful antioxidant that protects body from damage
caused by free radicals
Sporadic/ spontaneous cases:
* No hereditary cause (accounts for 90%)
* No clearly associated risk factors beyond age/sex
* Many hypotheses, include:
* heavy metal toxins,
* viral infections,
* or a combination of environmental and hereditary factors
The pathophysiology is unclear
* Likely mediated by complex interaction between molecular and
genetic pathways
* Theories include:
* increased cortical excitability
* reduced uptake of glutamate may lead to glutamate excitotoxicity
* mitochondrial dysfunction
* increased oxidative stress,
* Altered RNA processing
ALS A L S
Amyotrophic – A means no, myo means muscle, trophic means
nourishment “no-muscle-nourishment”
Lateral – the area of the spinal cord where the nerve cells that
innervate the hand are located
Sclerosis – hardening, the result of degeneration
* progressive, neurogenic disease that affects the upper and lower
motor neurons
ALS diagnosis
Difficult to diagnose
* Symptoms are similar to other neuromuscular disorders
* Patients must have symptoms of both upper and lower motor neuron
damage
* Not related to other causes
Diagnosis is usually based on a complete neurological examination
and clinical tests
* Some clinical tests are used to rule out other EXCLUDE neuromuscular disorders
1. EMG used to rule out myopathy
- rule out damage to muscle, is this a muscle problem vs nerve problem
2. Nerve conduction studies to rule out peripheral neuropathy
- see if it is peripheral nueropathy, if u kill motor nuerons, ones that still exist have high conduction velocities!
if u have slow conduction velocity then this is not likely that you have ALS (peripheral nueropathy)
3. MRI to rule out MS and other diseases
Symptoms:
lower motor=
weakness
atrophy muscle cells getting smaller
fasiculations
upper motor=
elevated tone
elevated reflexes
in ALS BOTHH
see EMG
- normal=mixed signal, muscles recruited randomly, keeps contractions smooth
- motor nueron disease, ALS, motor nuerons firing at same time, behavior of muscle to have more sychnronous firing of larger amplitude reflects one of the adaptations that happens in ALS, with lower motor nueron loss, early on, existing motor nuerons will synapse onto ones lost, disconnected, way more muscle cells attached to individual motor nuerons. NO smoothness, very few motor nuerons, lots of muscle cells (innervation ratio changed)
- lose a lot of motor nuerons before u notice it in ALS, early symptoms is fasiculations twitches, twitches r large in ALS, fasiculations more common in ALS
ALS EARLY SYMPTOMS
Early Symptoms
* Fasciculations: spontaneous muscle twitching
* Spasticity and/or cramping(upper motor nueron problem)
* Slight muscle weakness
* Particularly in hands, arms, legs, muscles of speech, swallowing,
breathing
- Symptoms can present as
primarily
‘upper motor neuron’ or
‘lower motor neuron’
- Up to 58% of motor neurons may be lost before
noticeable weakness or atrophy occurs
- hetrogeneous presentation, diff for each person!
-by the time ppl detecting, lots of damage done
ALS SYMPTOMS EARLY 2 diff ways of presentation
most damage in spinal cord motor nuerons, lower limbs coming on first
= Limb onset: 75%
* Earliest symptoms in limbs
* Tripping, stumbling, awkwardness during walking, and/or loss of
manual dexterity (e.g. writing)
most damage in corticol cranial nerves, the ones coming brainstem affected first
* Bulbar onset: 25%
* Earliest symptoms in face – slurred speech
* Typically have a more rapid decline in function with bulbar onset
all will be affected, present with 1 initially!
more symptoms ALS
Progressive Symptoms
* Eventually, movement problems spread to other body parts:
* Dysphagia=problem swallowing
* Dysarthria: difficulty forming words
* Hyperreflexia (UMN)
* Spasticity (UMN)
* Weakness and atrophy (primarily LMN)
* Fasciculations (LMN)
–>everything continues to progress
-COMMAND with not enough force
-trip, intention is to generste force, but muscle cant, so send more excitation which leads to fatigure, weakness
- not same as ATAXIA, nothing to do with coordination
ALS symptoms late stage
Complete loss of voluntary movement
- Weakness in ventilatory muscles
- Tracheostomy and mechanical ventilation often needed–>intubated
- Cognition is usually described as ‘most often preserved’
- Depression & anxiety is common
- vulvar cant live without
Death usually due to failure of either:
1. Diaphragm - Breathing
2. Swallowing muscles - Malnutrition, dehydration
ALS treatment
no treatment
- 1 drug FDA approved
- attempt in sort of reducing glutamate toxicity
- slows a little bit not in everyone
Riluzole (only drug FDA approved)
* Why it works in ALS is unclear
* Blocks some neurotransmitter receptors, potentiates others
* Appears to stimulate glutamate uptake
* Also blocks release of glutamate
* Perhaps reducing damage from neuron being overexcited by glutamate
* Prolongs survival by several months and can extend the time before a patient
needs ventilation support
* Does not reverse damage!
how does medications and therapy help ALS
Medications can also manage symptoms:
* Spasticity
* Fatigue
* Pain
* Depression
* Constipation
* Sleep problems
Physical therapy:
* Stretching, range of motion exercises
* Strengthening
* Help adapt to mobility aids
* Occupational therapy:
* Adapted functional activities
* Modify home to improve accessibility
* Assistive technology
* Speech therapy
* Swallowing assessment, work closely with dietitian
* Communication strategies
ALS symptoms:fasculations and atrophy
vulvar
- severe case
- fasiculations, twitching,
atrophy on tongue, shrunken, atrophy on tongue muscles
- severe
- late stage
- weakness in posture as well
- symptoms vary across people quite a bit
Myathenia Gravis
- nueromuscular junction disorder
Results from destruction/malfunction or an absence of one or
more key proteins involved in communication across
neuromuscular junction - nuerotransmitter problem, affects your ability to turn muscle on, still weakness,
- some issue with messaging between motor nueron and muscle
- nuerotransmitter not getting to muscle
- autoimmune disorder, own body kickinh out antibodies
Myasthenia Gravis Cause
- Uncertain what causes anti-bodies to bind to ACh receptors, but
abnormal thymus in 75% of cases (ach receptors important for motor nueron to communicate msg with muscle cell) ach goes from alpha motor nueron and open sodium channels - protein channels that bind to ach gets blocked, by antibodies, u release ach, does not have anything to connect to, not enough spots
- Start cascade that leads to destruction of receptor proteins
- Alters ability to stimulate muscle cells from motoneuron activity
eventually, receptor proteins r damaged, then progressive problems
- cant turn on muscle cells=fatigure
- long term = lead to damage that translates to muscle cell problems
-if maintain contraction longer, more antibodies come in and they cause u to fatigure quickly, contraction dies away even tho intention is to fire muscle
