Peripheral nervous system and Anterior horn disorders [3] Flashcards
Recognize the clinical features of: ALS
You know these ;)
Recognize the clinical features of: CMT
DISTAL weakness (normal center, small/atrophied hands and feet)
Most patients with CMT present with one of three phenotypes, based on the age at symptom onset. In the most common phenotype, the onset of walking is normal but distal (hands and feet) weakness and sensory loss develops slowly in the first two decades of life.
Patients rarely require ambulation aids other than foot braces (ankle foot orthoses – AFOs). Patients with the second phenotype are already impaired as infants and experience delayed walking. Many are confined to wheelchairs later in life. A third phenotype is defined as adult onset and may not appear until approximately 40 years of age
Recognize the clinical features of: DN
- Peripheral Polyneuropathy: Distal, glove and stocking sensory loss, Burning/stinging sensation distally
- Autonomic Neuropathy: Postural hypotension, Diarrhea, Tachycardia, Flaccid bladder, Impotence, Loss of sweating in hands and feet
- Mononeuropathy: Cranial Nerve III and/or IV involvement, Commonly entrapped median nerve
Recognize the clinical features of: MG
There are 2 clinical forms of MG:
- Ocular MG: weakness limited to the eyelids and extraocular muscles
- Generalized MG: weakness commonly affects ocular muscles, but also involves a variable combination of bulbar, limb, and respiratory muscles.
MG patients present with acute an onset of fluctuating weakness. The hallmark of myasthenia gravis is fatigability. Muscles become progressively weaker during periods of activity and improve after periods of rest. The physical exam can yield results within normal limits. Weakness is often asymmetric.
Facial weakness with trouble swallowing, Slurred speech, Shortness of breath (can progress to respiratory arrest), Neck muscle weakness, Proximal arm/leg weakness (can progress to quadriplegia), Opthalmoparesis (paralysis of one ore more extraocular muscles required for eye movements
Recognize the clinical features of: DMD
- Age of onset is 2-4 years old
- Early signs: lordosis, enlarged calves (pseudohypertrophy), Gower’s Maneuver, awkward gait
- Additional signs: toe walking, tripping, slow running, waddle, trouble on stairs, mental retardation (70%), enlarged tongue
- Often see progressive scoliosis
- Patients can develop contractures
How do you differentiate a mononeuropathy from a radiculopathy and plexopathy?
Mononeuropathy: disease of single nerve
Radiculopathy: disease of nerve roots
Plexopathy: disorder of nerve plexus
Plexopathies and Radiculopathies will have more wide-spread affects, such as cervical (neck) and lumbosacral (back) nerve root compression. Mononeuropathies affect only one nerve, such as in Carpel Tunnel syndrome and Ulnar nerve palsy
What are the pathologic changes of ALS?
ALS is characterized by progressive weakness and wasting resulting from degeneration of brainstem and spinal cord lower motor neurons. There is coexisting spasticity and hyperreflexia caused by degeneration of upper motor neurons
What are the pathologic changes of CMT?
Autosomal dominant CMT can be divided into 2 groups:
- Slow nerve conduction velocities (NCVs) and pathological evidence of a hypertrophic demyelinating neuropathy (CMT type 1)
- Relatively normal nerve conduction velocities and axonal degeneration (CMT2).
What are the pathologic changes of MG?
Disease of neuromuscular junction
The patient makes antibodies directed against the muscle-type nAChRs in the neuromuscular junction. This results in fewer receptors available for ACh binding, limiting depolarization and thus muscle contraction.
What are the pathologic changes of DMD?
On biopsy, the muscle from a DMD patient shows fibrosis, degeneration, and opaque muscle fibers.
On EM, there is a disruption in the plasma membrane called a delta lesion. IT makes a hole in the plasma membrane such that calcium can leak in. The increased concentration of intracellular calcium activates calcium-activated neutral protease and induces necrosis of the myofiber (calcium-induced necrosis).
What are the common genetic defects in DMD?
- Caused by a mutation in the Dystrophin gene, which is the largest gene in the human genome (79 exons and 8 promoters)
- Located on the X-chromosome
- Dystrophin is a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane
- Typically, DMD is caused by a point mutation resulting in a premature stop codon, resulting in a totally non-functional, truncated protein
What are the common genetic defects in CMT?
A variety of dominant, recessive and X-linked forms of CMT have been identified.
The most common form of CMT1A is a duplication of the DNA containing the peripheral myelin protein gene PMP22. (FYI, a deletion of the PMP22 gene also results in a neuropathy)
Describe the immune-pathogenesis and treatment of MG
MG results from autoantibodies that act against the muscle-type nAChR. Some forms of the antibody impair the ability of acetylcholine to bind to receptors. Others lead to the destruction of receptors, either by complement fixation or by inducing the muscle cell to eliminate the receptors through endocytosis.
Treatments: Thymectomy, Edrophonium (improvement with this drug is a diagnostic test), Prednisone, Azathioprine (inhibits T-cells)
Describe the symptomatic management of limb weakness and difficulty speaking, swallowing and breathing
Weakness:
Speaking: Therapy
Swallowing: Therapy (chin tuck, multiple swallows, clearing cough), Feeding tube (PEG)
Breathing: Respirator (invasive and non-invasive)
Upper motor neuron vs lower motor neuron disorders
Upper motor neuron (UMN) diseases produce spastic tone, hyperactive tendon reflexes, pathological reflexes (Babinski), and emotional lability (inappropriate laughing
and crying).
Lower motor neuron (LMN) signs include muscle atrophy, fasciculations, diminished tone and reduced or absent reflexes
