Motor Neuron Disease Flashcards
What do pyramidal tracts consist of?
The direct motor pathways that lead to activation of alpha motor neurons in the spinal cord (primary and associated motor cortex)
What do extrapyramidal tracts consist of?
Motor pathways that are indirectly involved in movement (BG and cerebellum)
Lower Motor Neuron Lesion
- weakness
- flaccidity
- fasciculations
- wasting/ atrophy
- areflexia
- decreased coordination
Upper Motor Neuron Lesion
- weakness
- increased tone
- spasticity
- clonus
- hyper reflexia
- decreased coordination
What does motor neuron disease occur from?
Primarily from damage to an upper or lower motor neuron resulting in denervation of voluntary muscles
What occurs to denervated muscle?
Quickly atrophies and cannot respond to voluntary control
Signs and symptoms of motor neuron disease
Weakness, atrophy, loss of function
Lesions of what structures can result is motor neuron disease?
Pyramidal tracts Alpha motor neurons in spinal cord or brain stem Nerve roots Nerves The neuromuscular junction
5 classifications of motor neuron diseases
Myelopathies (spinal cord disorders) Anterior horn cell disorders Nerve root lesions Peripheral nerve lesions Neuromuscular junction lesions
Myelopathies
Cervical spondylosis, spinal cord tumors, trauma
Anterior horn cell disorders examples
ALS, progressive nuclear palsy, polio and GB
Nerve root lesions examples
Cervical rib syndrome, acute intervertebral disc prolapse
Peripheral nerve lesions examples
Poly and mono-neuropathies
Diabetic neuropathy
Neuromuscular junction lesions
Myesthenia gravis
Characteristics of MND caused by Anterior horn lesions
- Affect anterior horn alpha motor neurons
- Age of onset: 30-60 yo
- Male predominance
- 90-95% of cases “sporadic”
- 5-10% of cases familial
5 Subclasses of Adult Anterior Horn Cell- MND
- Progressive nuclear palsy
- Pseudobulbar palsy
- Progressive spinal muscular atrophy
- Primary lateral sclerosis
- Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis
- Amyotrophy: Atrophy of muscle
- Lateral Sclerosis: hardening of lateral corticospinal tracts (lateral columns) due to gliosis
Population affected by ALS
- Males > females
- Caucasian
- Majority diagnoses between 40-70 yo (average 55)
Average life expectancy of ALS at time of diagnosis
3-5 years
Signs and symptoms of anterior horn cell disease (ALS)
- Muscle weakness (reduced power/force, pt complains of heaviness, clumsiness, fatigue)
- Atrophy/wasting
- NO CHANGE IN SENSATION
- progressive course
- fasciculations
- Areflexia
- Hypotonia
- NO WEAKNESS OF EXTRAOCULAR MUSCLES OR SPHINCTERS
Cognitive function in ALS
- Extent and level is uncertain and variable
- ranges from full frontotemporal dementia to neuropsychological, speech, or lingual deficits
Risk factors for ALS
- Older age
- Male gender
- Caucasian race
- Guamanian origin
(only blood lipids were linked to ALS risk)
Majority of cases of ALS are part of a continuum that includes ….
Frontotemporal dementia
- mutations in a DNA/RNA regulating protein C9ORF72
- leads to accumulation of cellular RNA and/or proteins that are toxic
What is the primary protein product that accumulated with Frontotemporal dementia/ALS?
TDP-43
What do C9ORF72 mutations lead to?
dysregulation of RNA processing, leading to toxic cellular accumulations
Autophagy
Recent studies also indicate autophagy is important in diagnostic development
Role of Autophagy in Disease
- up and down regulated in response to growth signals and environmental ques
Autophagy role in cancers
- Protects against cancer by controlling growth
- down-regulation confers a survival advantage in some cancers
Role of autophagy in neurogenerative disease
- many NDDs are characterized by age-dependent neuronal death due to accumulation of normal proteo-metabolism products: Tau & beta amyloid, huntintin, and alpha-synuclein
- Involves the tagging and clearance of these proteins and is the body’s only mechanism for disposal
ALS is characterized by accumulation ….
TDP43
3 general “forms” of ALS
- Sporadic
- Familial
- Guamanian
Sporadic ALS
most common (90%)
Familial ALS
- typically autosomal dominant inheritance pattern
- accounts for only 10% of cases
- individuals with inherited forms have 50% of passing it on
- 20% have superoxide dismutase mutation
Guamanian ALS
based on high incidence in Guam and Trust Territories in 1950s
Potential Retrovirus Association & other Environmental Stimuli
- HERV is + in many cases
- Cyanobacteria, heavy metals, pesticides, intense physical activity, head injury, smoking, electromagnetic field or electric shock exposure
Cyanobacteria are linked to the high incidence in Guam, secondary to ….
dietary factors
Bulbar weakness (20% of cases)
- difficulty chewing and swallowing
- coughing
- dysarthria and dysphagia
- dyspnea
- dasciculation
- decreased respiratory muscle strength: often progressive and the primary cause of death
- no sensory loss and extra ocular muscles and sphincters typically spared
Limb weakness (80% of cases)
- upper extremity muscle affected first in 50% of cases
- fatigue-ability
- weakness
- cramping
- muscle twitching
- wasting
- stiffness
- speech, swallowing, respiration
- cognitive function not typically affected
Primary lateral sclerosis
- exclusively upper motor neuron involvement
- improved survival compared to PMA
Progressive muscular atrophy
- exclusively lower LMN involvement
Differential Diagnosis of ALS- Presentation
- strength testing: mapping weakness allows differentiation of spinal/nerve or NMJ from anterior horn cell lesion
- often involves muscles of chewing, speaking, swallowing, no involvement of extra-ocular muscles or sphincters
- Sensation testing: normal
Differential Diagnosis of ALS- Special Tests
- MRI, CT, and X-Ray to rule out other conditions
- EMG: shows partial chronic partial denervations (few voluntary motor units, spontaneous activity in resting muscle)
Most common misdiagnoses in ALS
- Cerebral lesions: especially with C/S or L/S root involvement
- Cervical spondylosis myelopathy
- Conus medularis lesion
- inclusion body myositis
- Cramp/fasciculation syndromes
- multifocal motor neuropathy
- Kennedy’s disease
Progression of ALS
- progressive weakness leads to respiratory failure and/or aspiration pneumonia
- pulmonary infections
- malnutrition
- fatal outcome within 2-5 years of DX
- Bulbar involvement worse than spinal type
Evaluation of ALS
- Vital signs, dyspnea scale, SaO2
- pulmonary function testing
- careful muscle strength testing
- sensation testing
- cranial nerve testing
- cognitive testing
- mobility/transfer tests
- QoL
ALS Functional Rating Scale
- Estimates the patients degrees of functional impairment
- 10 questions require rater to give impression of patient’s level of functional impairment on performing common tasks
- 5 point scale
- scores summed with 40= best possible
- shown to have satisfactory internal consistency and reliability
Treatment of ALS
- Edaravone
- Antisense oligonucleotide silencing of FUS expression –> Jacifusen
- miR-340
- Riluzole
- Anticholinerics
- Mechanical ventilation
- Feeding tube
- Telbivudine for hepatitis
PT related treatment of ALS
- Active ROM
- AAROM
- PROM
- Positioning
- Respiratory/chest PT
- Inspiratory muscle training
Reparatory/Chest PT
- Percussion, vibration, mechanical vibrators or precursors
- Postural drainage
- Cough assist technique
Inspiratory muscle training
Weight versus inspiratory trainer or inspiratory spirometer
What should be used to slow ALS disease progression
Riluzole
What should be used to stabilize weight and prolong survival of ALS
PEG
What should be considered to treat respiratory insufficiency
NIV
Does Riluzole provide a beneficial effect on strength?
no but it does provide a small beneficial effect on other bulbar and limb function
What is likely the most effective treatment for ALS
Riluzole
Occupational therapy for ALS
- increasing independence around the home
- equipment to assist in ADLs
Physical therapy for ALS
- assistive devises
- braces
- teach transfers
- ROM to prevent contractures/DVT
General principles for therapy for ALS
- “text to speech” software devices allow pt to communicate
- maximize function by adaptation/technology
- instruct care giver in assisting patient
- adapt environment for patient
3 Classes of Neuromuscular Junction Disorders
- Disorders involving Ca-mediated exocytosis of acetylcholine:
1. Blockage of Ca channels: Lambert Eaton Syndrome
2. Impaired Ca-mediated release of Ach: Botulism - Disorders of the Ach receptor
3. Antibody induced down regulation of Ach receptors: Myasthenia Gravis
Lambert Eaton Syndrome
- Autoimmune disease in which the presynaptic neuromuscular junction Ca2+ channels are damaged or destroyed by antibodies
- Decreased Ach release
- Characterized by weakness and areflexia that improve with sustained contraction
- Rx based on combination of K+ channel blocker and Ca2+ channel agonist
Myasthenia Gravis
Immune mediated disease involving fluctuating weakness and easy fatigue ability of voluntary muscles
- associated with thymus tumor, thyrotoxicosis, RA, Lupus erythmataosus
- females > males
- predilection for the external ocular and other cranial muscles
myasthenia gravis presentation
- diplopia
- ptosis
- dysarthria
- LE weakness
- generalized weakness
- dysphagia
- sustained muscular effort impaired, while brief effort is normal
- reflexed normal and little atrophy
Diagnosis of Myasthenia Gravis
- Single fiber electromyography
- E-stim facial nerve, observe rate of fatigue twitch
- administer cholinesterase inhibitor: have patient do repeated voluntary contractures; if symptoms improve, test is +
- check for thymoma or hyperthyroidism
- immunological testing
- nerve conduction velocity is normal
- single fiber EMG shows increase variability in interval between twitches
- pulmonary function test
Myasthenia Gravis Etiology
- patients develop antibodies to Ach receptors or to muscle specific kinase or LDL receptor related protein
- may be due to thyme follicular hyperplasia
- pro inflammatory environment contributes
- leads to Ach receptor damage and loss, making it difficult to stimulate muscles
Differential Diagnosis of MG- Critical Illness polyneuropathy
severe, systemic weakness, associated with critical illness, sepsis and multi organ failure
Differential Diagnosis of MG- Critical Illness Myopathy
- acute onset of severe diffuse weakness including respiratory muscles and loss of DTR
- associated with steroid use and/or neuromuscular blockage
- elevated serum CK and MG levels
Disease characteristics of MG
- insidious onset
- Average age: 28 women, 42 males
- slowly progressive, fluctuating course
- managed with medications but difficult to cure
- may ultimately be fatal- due to respiratory infections or complications
Treatment of MG
- Cholinesterase inhibitors
- Thymectomy
- Corticosteroids
- Azathioprine and Mycophenolate (immunotherapy)
- Plasmapheresis
- IV immunoglobulins
PT for MG
- maximize function
- adapt environment
- educate/train caregiver
- active exercise must be administered carefully and in small doses secondary to easily fatigued and may lead to exhaustion
