Peripheral Nervous System and Skeletal Muscle Pathology (Martin) Flashcards
Segmental demyelination occurs when?
What is the classic disease process of this?
1) There is dysfunction of Schwann cell and damage to the myelin sheath
2) Guillain-Barre
With segmental demyelination, what happens to the axon and myocytes?
Remain intact
A failure of the outgrowing axons to find their distal target can produce a non-neoplastic whorled proliferation of axonal processes and associated Schwann cells that results in a painful nodule termed?
Traumatic neuroma
Muscle fiber type is determined by?
Motor neuron
With axonal degeneration, muscle fibers in motor unit lose neural input and undergo?
Denervation atrophy
What are atrophic fibers that are smaller & triangular shape when denervation atrophy occurs?
What are rounded zone of disorganized myofibers in the center of the fiber?
1) Angulated fibers
2) Target fibers
A patch of contiguous myocytes having the same histochemical type is known as?
Type grouping
What causes type 2 fiber atrophy?
1) Inactivity or disuse
2) Glucocorticoid therapy
Segmental necrosis is the result of?
The loss of muscle fiber leads to?
1) Destruction of a portion of myocyte, followed by myophagocytosis
2) Deposition of collagen and fat
What happens to muscle fibers during hypertrophy?
They divide longitudinally (Muscle fiber splitting)
Patients with peripheral neuropathy (PN) generally describe the pain as?
Pins and needles
What causes several nerves to be damaged in haphazard fashion?
What is a common cause of this pattern?
1) Mononeuritis multiplex
2) Vasculitis
What does Bell’s Palsy result in?
What CN is involved?
What is it associated with?
1) Unilateral facial droop
2) CN VII
3) URI and DM
Neurogenic bladder which causes lack of bladder control can be the result of diseases/defect such as?
1) MS
2) Parkinson’s
3) Diabetes
4) Spina bifida
What is Guillain-Barre?
Acute inflammatory demyelinating polyneuropathy
How is the paralysis characterized in Guillain-Barre?
What happens to the DTRs as it progresses?
1) Ascending paralysis
2) Disappear
Guillain-Barre results in radiculoneuropathy, what does that term mean?
Inflammation and demyelination of spinal nerve roots and peripheral nerves
2/3 of cases of Guillain-Barre are preceded by?
Most commonly from?
What antibodies are present?
1) Acute influenza-like illness
2) Campylobacter jejuni
3) Anti-myelin Abs
What do we see in the CSF with Guillain-Barre?
1) Increased protein
2) Little or no CSF pleocytosis
What is the treatment for Guillain-Barre?
1) Plasmapheresis
2) IVIG
What are the most common acquired inflammatory peripheral neuropathy?
Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy
The symmetrical mixed sensorimotor polyneuropathy seen in Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy must persist for how long in order for it to be classified as chronic?
2 months
What distinguishes Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy from Guillain-Barre?
Time course and response to steroids
The excessive Schwann cell proliferation seen with Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy results in what appearance?
Onion bulbs
In regards to Lepromatous Leprosy, what pathogen invades Schwann cells, proliferates, then infects other cells?
Mycobacterium leprae
What happens to the axons with Leprosy?
What happens to the endoneurial and perineural sheaths?
1) Loss of myelinated and unmyelinated axons
2) Endoneurial fibrosis and thickening of perineural sheaths
What is the clinical presentation of leprosy?
1) Symmetric polyneuropathy affecting the distal (cool) extremities and face
2) Involves pain fibers leading to loss of sensation which contributes to injury
With Lepromatous Leprosy, smears are positive for what stain at any location?
AFB stain
Diphtheria exotoxin affects peripheral nerves and causes an early loss of what sensations?
There is selective demyelination of axons that extend into adjacent?
1) Proprioception and vibratory sensation
2) Anterior/posterior roots and mixed sensorimotor nerves
What is the most common viral infection of PNS?
Varicella-Zoster virus
Varicella-Zoster affects what areas of the spinal cord and brainstem?
Reactivation occurs in what nerves?
1) Sensory ganglia
2) Trigeminal nerves
How does the reactivation of latent infection of Varicella-Zoster present?
Painful, vesicular skin eruption (shingles) in a sensory dermatomal pattern
What occurs to the peripheral nerves with Varicella-Zoster?
There is focal destruction of large motor neurons in what areas?
1) Axonal degeneration of peripheral nerves after death of sensory neurons
2) Anterior horns or cranial nerve motor nuclei
What is the most common cause of peripheral neuropathy?
Diabetes
What is the most common polyneuropathy pattern seen with diabetes?
Ascending distal symmetric sensorimotor polyneuropathy
Diabetes mellitus is the number one cause of?
Non-traumatic limb amputations
Segmental demyelination seen with DM neuropathy results in?
What happens to the endoneurial arterioles?
1) Loss of small myelinated fibers and unmyelinated fibers
2) Thickened vessel wall that is PAS+
The dysfunction of autonomic nervous system seen in 20-40% of DM patients leads to what symptoms?
1) Postural hypotension
2) Incomplete emptying of bladder
3) Sexual dysfunction
What is the most common Paraneoplastic neuropathy?
What is it associated with?
1) Sensorimotor neuronopathy
2) Small cell lung cancer
Neuropathies associated with monoclonal gammopathies (B-cell neoplasms) results in what syndrome?
POEMS syndrome:
1) Polyneuropathy
2) Organomegaly
3) Endocrinopathy
4) Monoclonal gammopathy
5) Skin changes
Carpel tunnel syndrome affects what nerve?
Numbness & paresthesia is noted at what digits?
1) Median nerve
2) Thumb and first 2 digits
Saturday night palsy affects what nerve usually due to falling aspleep awkwardly?
Radial nerve
What is the most common inherited peripheral neuropathies?
Charcot-Marie-Tooth Disease
Myasthenia gravis has antibodies to?
Acetylcholine receptors
10% of MG patients have?
30% of patients have?
1) Thymoma
2) Thymic hyperplasia
Myasthenia Gravis presents with fluctuating generalized weakness that worsens with?
Diminished responses are seen after?
Weakness begins with extraocular muscles leading to?
1) Exertion and over the course of the day
2) Repeated stimulation
3) Diplopia, fatigue, ptosis
Lambert-Eaton myasthenic syndrome has antibodies to?
What does this cause?
1) Voltage gated calcium channels
2) Blocks Acetylcholine release
50% of Lambert-Eaton myasthenic syndrome patients have an underlying malignancy, often?
Neuroendocrine carcinoma of the lung
Repetitive stimulation has what affect in Lambert-Eaton myasthenic syndrome patients?
Increases muscle response, opposite of MG
With diseases of skeletal muscle in adult tissue, what can contribute to muscle regeneration following injury?
Satellite cells (small pool of tissue stem cells)
What do we see in skeletal muscle with neurogenic diseases?
Fiber type grouping and group atrophy
What is myofiber hypertrophy?
Physiologic adaptation to exercise
Dermatomyositis leads to what specific type of atrophy?
Perifascicular atrophy
What distinctive skin rash is seen with dermatomyositis?
What is this due to?
What scaling erythematous eruption or dusky red patches can be seen over the knuckles, elbows and knees?
1) Lilac or heliotrope discoloration of upper eyelids associated with periorbital edema
2) Telangiectasias
3) Gottron papules
What classic symptomology is seen with dermatomyositis?
Proximal muscle weakness so difficulty getting up form chair and climbing stairs
What autoantibodies associated with dermatomyositis cause the heliotrope rash and Gottron papules?
What causes “mechanic’s hands”?
What causes paraneoplastic & juvenile type?
1) anti-Mi2
2) anti-Jo1
3) anti-P155/P140
What is the most common inflammatory myopathy in children?
Juvenile type dermatomyositis
Adult onset inflammatory myopathy with myalgia and symmetric, proximal weakness is characteristic of?
Polymyositis
How does polymyositis differ from dermatomyosisits?
No cutaneous involvement
What is the most common inflammatory myopathy in patients > 65?
Inclusion Body Myositis
Inclusion Body Myositis is most severe in what areas of the body?
Quads and distal upper extremities
What morphologic change is seen in Inclusion Body Myositis?
Rimmed vacuoles (Abnormal cytoplasmic inclusions)
What is the first line treatment for inflammatory myopathies?
Corticosteroids
Which inflammatory myopathy responds poorly to steroids or immunosuppressive treatment?
Inclusion body myositis
What is a cause of toxic myopathy regardless of dose or subtype?
Statins
What causes drug-induced lysosomal storage myopathy and leads to slowly progressive muscle weakness?
What fiber type is affected?
1) Chloroquine and hydroxychloroquine
2) Type 1
What leads to proximal muscle weakness, exophthalmic ophthalmoplegia, and hypothyroidism?
Thyrotoxin myopathy
Binge drinking may produce?
Rhabdomyolysis
Congenital Muscular Dystrophy: Ullrich Congenital Muscular Dystrophy (UCMD) is due to mutation of one of the three?
Collagen VIα genes
Which X-linked Muscular Dystrophy is more common and more severe?
Duchenne
What gene is affected with Duchenne muscular dystrophy?
Dystrophin
When does Duchenne’s present?
When does Becker’s?
1) Before 5 yo
2) Late childhood
What is the difference between DMD and BMD in terms of dystrophin?
1) No dystrophin
2) Decreased amount of dystrophin
What symptoms is seen with DMD?
Pseudohypertrophy of calves
Immunohistochemical staining pattern for DMD shows?
Absence of the normal sarcolemma
What levels are drastically increased in the first decade of life with DMD?
Serum CK
Symptoms of skeletal muscle weakness, cataracts, endocrinopathy and cardiomyopathy point towards?
Myotonic Dystrophy
What mutation is seen with Myotonic Dystrophy?
Due to?
1) DMPK mutation
2) CTG expansion
Symptoms of slowly progressive humeroperoneal weakness, cardiomyopathy (conduction defects), early contractures of Achilles tendon, spine, and elbows points towards?
Emery-Dreifuss Muscular Dystrophy
Myophosphorylase deficiency is characteristic of?
Acid maltase deficiency with generalized glycogenesis of infancy is characteristic of?
1) McArdle disease
2) Pompe disease
Weakness, increased serum CK, or rhabdomyolysis along with extraocular muscle involvement and chronic progressive external ophthalmoplegia are symptoms that point to?
Mitochondrial myopathies
Autosomal recessive neuropathic disorder with loss of motor neurons leading to muscle weakness and atrophy is characteristic of?
Infants with this disease present as?
1) Spinal Muscular Atrophy
2) Floppy baby (Wernig-Hoffman)
Spinal Muscular Atrophy destroys what area of the spinal cord?
It is caused by what mutation?
1) Anterior horn cells
2) SMN1
What is the most common Ion cannels Myopathies (channelopathies) mutation?
What is it associated with?
1) RYR1
2) Malignant hyperthermia
What is a familial tumor syndrome that is generally seen in children?
What tumors is it associated with?
What are the cutaneous lesion shagreen patches characterized by?
What are the Ash-leaf patches?
1) Tuberous sclerosis complex
2) Hamartomas
3) Localized leathery thickenings
4) Hypopigmented areas
Neurofibromas of peripheral nerves, optic nerve gliomas, Lisch nodules, and Café au lait spots points towards?
Neurofibromatosis (NF) type 1
What is characterized by bilateral schwannomas (CN VIII) and increased meningiomas, ependymomas?
NF type 2
What are Schwannoma positive for?
S-100
Plexiform Neurofibroma has what characteristic appearance?
Bag of worms
