Chapter 22: Peripheral Nerves and Muscles
The two major functional elements of peripheral nerves.
axonal processes and myelin sheaths
Neuropathies that are caused by insults that directly injure the axon.
The term used to describe changes observed in axonal neuropathies.
The morphologic hallmark of axonal neuropathies.
a decrease in the density of axons
Neuropathies characterized by damage to Schwann cells or myelin with relative axonal sparing.
The effect of demyelinating neuropathies on conduction velocity and amplitude.
slow conduction velocity but preserved amplitude
The term used to describe the discontinuous pattern of demyelination seen in demyelinating neuropathies.
Peripheral neuropathies that:
- affect peripheral nerves in a symmetric, length-dependent fashion
- have a “stocking-and-glove” distribution
- are often encountered with toxic and metabolic damage
Peripheral neuropathies that:
- randomly affects individual nerves
- may result in wrist drop or foot drop
- are often caused by vasculitis
Peripheral neuropathies that:
- involve a single nerve
- are most commonly the result of trauma or infection
A rapidly progressive acute demyelinating disorder affecting motor axons, resulting in ascending weakness that can lead to death from failure of respiratory muscles within days of onset of symptoms.
The most common peripheral neuropathy, characterized by symmetrical mixed sensorimotor polyneuropathy that persists for 2 months or more.
chronic inflammatory demyelinating polyneuropathy (CIDP)
The most common cause of peripheral neuropathy, usually developing with long-standing disease.
A form of diabetic neuropathy characterized by changes in bowel, bladder, cardiac, or sexual function.
A form of diabetic neuropathy that usually manifests with asymmetric pain that can progress to lower extremity weakness and muscle atrophy.
The most common form of diabetic neuropathy, which primary affects sensory axons, resulting in paresthesias and numbness.
distal symmetric sensorimotor polyneuropathy
Etiological categories of peripheral neuropathies. (6)
An autoimmune disease with fluctuating muscle weakness that is caused by autoantibodies that target the neuromuscular junction.
The most common antigenic target in myasthenia gravis.
postsynaptic acetylcholine receptor (AChR)
Most frequent clinical manifestations of myasthenia gravis.
ptosis (drooping eyelids) or diplopia (double vision)
A disease caused by autoantibodies that inhibit the function of presynaptic calcium channels, thereby reducing the release of acetylcholine into the synaptic cleft.
Carcinoma most commonly associated with Lambert-Eaton syndrome.
small cell lung carcinoma
A heterogeneous group of diseases that result from mutations that disrupt the function of various neuromuscular junction proteins.
congenital myasthenic syndromes
Exotoxin-producing bacteria associated with defects in neural transmission and muscle contraction. (2)
Clostridium tetani and Clostridium botulinum
A toxin that blocks the action of inhibitory neurons, leading to the increased release of acetylcholine and sustained muscle contraction and spasm.
tetanus toxin (tetanospasmin)
A toxin that inhibits acetylcholine release, producing a flaccid paralysis.
One lower motor neuron together with the associated axon, its neuromuscular junctions, and the skeletal muscle fibers it innervates.
Two classifications of skeletal muscle fibers.
slow twitch type I and fast twitch type II fibers
The complex of glycoproteins that couples the muscle cell sarcolemma to extracellular matrix proteins and the intracellular cytoskeleton
dystrophin-glycoprotein complex (DGC)
Morphological change associated with both primary muscle diseases and secondary neuropathic changes.
muscle fiber atrophy
The two main morphologic hallmarks of neurogenic muscle diseases.
grouped atrophy and fiber type grouping
Iatrogenic cause of focal or generalized muscle atrophy, which tends to affect type II fibers more than type I fibers.
prolonged disuse of muscles (e.g. bed rest, cast)
Pharmacological cause of muscle atrophy, which tends to affect proximal muscles and type II myofibers are affected preferentially in this setting.
Muscular disorder associated with progressive muscle injury in patients who have normal muscle function at birth.
Progressive, early-onset muscular diseases associated with malformations of the central nervous system.
congenital muscular dystrophies
Present in infancy with muscle defects that tend to be static or to even improve with time, often associated with distinct structural abnormalities of the muscle.
The protein most commonly affected X-linked mutations in muscular dystrophies.
Two most important dystrophinopathies.
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD)
Dystrophinopathy that typically presents as clumsiness and an inability to keep up with peers because of muscle weakness.
Duchenne muscular dystrophy (DM
Dystrophinopathy that becomes symptomatic later in childhood or adolescence and progresses at a slower and more variable rate.
Becker muscular dystrophy (BMD)
The cardinal neuromuscular symptom in myotonic dystrophy.
Protein most commonly affected by mutations in myotonic dystrophy.
dystrophia myotonica protein kinase (DMPK)
Term used to describe worsening of nucleotide repeat expansion diseases with each passing generation because of further trinucleotide repeat expansion.
These muscular dystrophies preferentially affect the proximal musculature of the trunk and limbs.
limb-girdle muscular dystrophies
A genetically heterogeneous disorder caused by mutations affecting structural proteins found in the nucleus.
Emery-Dreifuss muscular dystrophy (EMD)
An autosomal dominant form of muscular dystrophy that is caused by complex genetic changes that allow expression of the transcription factor DUX4 that is normally repressed in mature tissues.
A group of familial disorders caused by inherited defects in ion channels that are characterized by myotonia, hypotonic paralysis, or both.
ion channel myopathies
Results from mutations in the gene encoding the skeletal muscle sodium channel SCN4A, which regulates sodium entry during contraction.
hyperkalemic periodic paralysis
Triggered when patients carrying mutations in RYR1, a calcium efflux channel, receive halogenated anesthetic agents or succinylcholine during surgery
Myopathies caused by disorders of glycogen synthesis and degradation and lipid handling.
myopathies due to inborn errors of metabolism
Myopathies that stem from mutations in either the mitochondrial or nuclear genomes.
A blotchy red appearance in special stains produces by aggregates of abnormal mitochondria in mitochondrial myopathies.
ragged red fibers
The traditional triad of inflammatory myopathies.
polymyositis, dermatomyositis, and inclusion body myositis
An autoimmune disorder associated with increased expression of MHC class I molecules on myofibers and predominantly endomysial inflammatory infiltrates containing CD8+ cytotoxic T cells.
The most common inflammatory myopathy in children, often manifesting as a paraneoplastic disorder in adults, typically associated with skin manifestations.
The most common inflammatory myopathy in patients older than 60 years of age, characterized by the presence of rimmed vacuoles that contain aggregates of proteins that accumulate in neurodegenerative diseases.
inclusion body myositis
A cause of toxic myopathy thatmay take the form either of acute or chronic proximal muscle weakness, and it can be the first indication of thyrotoxicosis.
A cause of toxic myopathy that occurs after an episode of binge drinking, which may lead to acute renal failure secondary to myoglobinuria.
A cause of toxic myopathy that most commonly occurs as a complication of statins (e.g., atorvastatin, simvastatin, pravastatin).
Two forms of statin associated myopathy.
(1) toxicity of the drug and (2) statin-induced HMG-CoA reductase autoantibodies
Benign encapsulated tumors that may occur in soft tissues, internal organs, or spinal nerve roots.
Cranial nerve most commonly affected by schwannomas.
vestibular portion of the eighth cranial nerve (vestibulocochlear nerve)
A hereditary condition most commonly associated with bilateral vestibular schwannomas.
familial neurofibromatosis type 2 (NF2)
Dense areas of schwannomas consisting of bland spindle cells with buckled nuclei are arranged into intersecting fascicles.
Loose, hypocellular areas of schwannomas consisting of spindle cells spread apart by a prominent myxoid extracellular matrix.
Benign peripheral nerve sheath tumors.
Neurofibromas that arise as superficial nodular or polypoid tumors.
localized cutaneous neurofibromas
Neurofibromas that grow diffusely within the confines of a nerve or nerve plexus.
Neurofibromas that are infiltrative proliferations that can take the form of large, disfiguring subcutaneous masses.
An autosomal dominant disorder caused by mutations in the tumor suppressor neurofibromin, encoded on the long arm of chromosome 17 (17q).
neurofibromatosis type 1 (NF1)
Neoplasms seen in adults that typically show evidence of Schwann cell derivation and sometimes a clear origin from a peripheral nerve.
malignant peripheral nerve sheath tumors
A nonneoplastic proliferation associated with a previous injury leading to transection of a peripheral nerve.