Neuromuscular diseases week 6 Flashcards
What are the differences btwn neuronopathy, axonopathy, and myelinopathy.
neuronopathy: pathology in cell body
axonopathy: pathology in axon
myelinopathy: pathology of myelin
Explain the differences in affects on strength and muscle atrophy when there is segmental demyelination vs axonal degeneration vs myopathy.
In segmental demyelination, there is no muscle atrophy because the muscles are still innervated, however, the person experiences weakness.
In axonal degeneration, there is muscle atrophy (due to deinnervation) that is regained with reinnervation (by regrowth of axon and/or nearby axons).
In myopathy, the pathology is in the muscle so there may be atrophy, inflammation, etc of the muscles.
In neuronopathy, what are the pathologic mechanisms?
What sensory ganglions may be affected?
What part of the axon degenerates first? What part of the axon degenerates following this?
Neuronopathy
- Pathologic mechanisms often not clear
- Multiple etiologies
- Sensory - Dorsal root and gasserian (aka trigeminal) ganglions vulnerable
- Degeneration of neuronal perikaryon (cell body)
- Degeneration of axon follows
- Regeneration?
What is amyotrophic lateral sclerosis (ALS)?
What are the clinical features of ALS?
What is the percentage of sporadic and familial cases of ALS?
What sex is ALS more prevalent in?
What mutation is present in familial cases? What are possible causes in sporadic cases?
How is ALS diagnosed? What is the prognosis?
ALS: Degenerative disorder of the upper and lower motor neurons.
Upper Motor Neuron signs
- weakness
- spasticity
- hyperreflexia
- babinski sign, jaw jerk
Lower Motor Neuron signs
- weakness
- fasciculations
- atrophy
- hypotonia
men ≥ women, 90% sporadic vs 10% familial
Time to diagnosis from clinical onset ( 70% limb, 30% bulbar) up to 18 months . Time from diagnosis to death 2-5 years with a range of 1.5- 20 years. Diagnosis by clinical and electrophysiological (El Escorial) criteria. There are no specific laboratory tests for ALS.
Causative agent presumed to be mutant SOD1 in familial cases of ALS with defined SOD1 mutations (Other mutations include TDP43, FUS, ALSIN). In sporadic cases cases multiple causes have been proposed include neuroinflammation, excitotoxicity.
What is spinal muscular atrophy?
What are the clinical signs?
What mutation is responsible?
What is the prognosis?
Spinal Muscular Atrophy
- Loss of alpha-motor neurons leads to lower motor neuron signs
- Hypotonia, symmetrical weakness, hypoventilation, swallowing difficulties (prevalence: 1/80 carrier state)
- Death by age 2
- SMN protein required for assembly of snRNP splicing complexes. A silent nucleotide change in SMN2 results in skipping of exon 7 —> predominate production of an unstable protein. see attached pic
Generally, what may cause demyelination of peripheral nerves?
Generally, what may cause axonal damage to peripheral nerves?
Peripheral Neuropathy: Classification by pathologic process
Demyelinating
- Immunologic damage to Schwann cells (GBS)
- Genetic defect in Schwann cells (HSMN-1)
Axonal
- Metabolic failure of ganglion cells (DM)
- Ischemic damage to endoneurium (vasculitis)
- Toxic damage to endoneurium (amyloidosis)
What are examples of generalized symmetric, focal, and multifocal causes of peripheral neuropathy?
Peripheral Neuropathy: Classification by anatomic distribution
Generalized symmetric
- Length-dependent (toxic,metabolic) : the longest axons are affected first and most severely. Remember that cell bodies must provide metabolic and other support to axons. For neurons in the extremities, the cell body may be far away from the tip of the axon. In this type of neuropathy, would see sx first in the feet, for example, that would move up to the hands.
- Non-length dependent (immunologic)
Focal
- Mononeuropathy (carpal tunnel sydrome)
Multifocal
- Mononeuropathy multuplex (vasculitis)
What does symptoms does neuropathy cause?
Neuropathy causes weakness and atrophy of muscle, loss of sensation or altered sensation (pain, paresthesias), and reduced or absent tendon reflexes.
In distal axonopathy, in what part of the axon may the pathology be?
What is the cause of distal axonopathy?
What happens to distal muscles in this disorder?
Distal axonopathy
- Disturbance in cell body or throughout axon
- Failure of axonal transport
- Distal regions of axons most vulnerable “Length-dependent”
- Degeneration advances proximally
- Distal muscles undergo denervation atrophy
What are the common causes of distal axonopathy?
Distal axonopathy: Common Causes
- Toxic (alcohol)
- Metabolic (diabetes, uremia)
- Hereditary (HMSN type II)
- Malignancy associated
What is the diagnosis?
Acute inflammatory demyelination polyneuropathy (Guillan-Barre syndrome)
Explain the clinical presentation of Guillan-Barre syndrome.
What are the laboratory findings?
What is nerve conduction velocity like in this disease?
What is the most important criteria for diagnosis of AIDP?
When is maxium severity of symptoms observed in this disease?
Acute inflammatory demyelinating polyneuropathy (AIDP) : Guillain-Barré Syndrome
- Clinical presentation: ascending paralysis, progressive (over hours to days) weakness of more than 2 limbs, areflexia, predominantly motor
- Laboratory findings - elevated CSF protein with relatively normal cell count, slowing of nerve conduction velocities/conduction block
- Respiratory involvement in ~25%
- The most important criterion for AIDP/GBS is that the disease must have an acute onset.
- Progression of symptoms is observed over several days to weeks, with maximum severity reached within 4 weeks of onset
- Areflexia or hyporeflexia is observed within one week of symptom onset
What is myelinopathy?
Name causes for myelinopathy.
A disorder affecting the myelin of peripheral nerve fibers.
Myelinopathies: Causes
- Immunologic
- AIDP
- CIDP (chronic inflammatory demyelinating polyneuropathy)
- Toxic (Diphtheria)
- Hereditary (Charcot-Marie-Tooth [CMT] type I) First Aid: AKA hereditary motor and sensory neuropathy (HMSN). group of progressive hereditary nerve disorders related to the defective production of proteisn involved in the strucutre and function of peripheral nerves or the myelin sheath
What is the diagnosis?
“Droopy Eyelids”
- A 28 year old previously healthy man
- Developed double vision 4 months ago
- “Droopy” eyelids toward the end of the day
- Mild increased fatigue in arms and legs
- “Hard to type for more than 20 minutes”
- Had previous episode of double vision that resolved
- No chronic medical issues
- Currently taking NO medications
- Family History
- Maternal aunt with “lupus”
Myasthenia gravis
What is myasthenia gravis?
What is the clinical presentation of someone with myasthenia gravis?
Explain the range in severity of symptoms in myasthenia gravis.
Myasthenia gravis
- Autoimmune disorder of neuromuscular transmission
- Incidence: 1-2/100,000
- Prevalence: 20-50/100,000
- Weakness, fatigability
- Severity can range from mild ocular symptoms to severe limb weakness and respiratory failure
Clinical Presentation
- Fatigable weakness
- Extraocular muscles
- Facial/bulbar muscles
- Limb muscles
- Respiratory muscles
- Respiratory/bulbar weakness may be life threatening