Robbins - Peripheral Nerves and Muscles (Ch. 27) Flashcards
3 common causes (general) of mononeuropathies
Trauma
Entrapment/impingement
Infections/malignancy
Polyneuropathies - how do they generally present?
Symmetric, start in hands/feet and ascend (“Stocking and glove” distribution)
Common cause of mononeuritis multiplex
Vasculitis
Polyradiculoneuropathies also involve the ____, leading to symmetric symptoms in the distal AND ___ body
Nerve roots
Proximal
Acute motor weakness or paralysis in hands and feet that rapidly progresses to proximal muscles. DTRs are absent. Recently was sick.
What is it?
What PMH questions would you ask?
Worst complication?
Guillain-Barré Syndrome (Acute Inflammatory Demyelinating Polyneuropathy)
Autoimmune-mediated inflammation and demyelination of peripheral nerves and spinal nerve roots
Recent pneumonia? Recent viral illness? Recent GI infection?
Respiratory paralysis
Guillan-Barré – inciting incident? Which ones?
INFECTION
- Mycoplasma pneumonia
- C. jejuni enteritis
- HIV, CMV, EBV viral illness
Diagnosing Guillan-Barré (3)
- CSF protein elevated
- No CSF pleocytosis
- Slow nerve conduction
Treating Guillan-Barre´ (2)
- Plasmapheresis
- IVIG
Relapsing and remitting symmetric sensory and motor deficits in the extremities for the past 2+ months. IgG and IgM are found on the myelin sheaths of peripheral nerves. Responds well to steroids.
Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Systemic autoimmune diseases that can cause sensorimotor neuropathy (3)
RA, Sjogren, SLE
Loss of pain and sensation in all distal extremities and face. Segmental demyelination is found. Large ulcers found on extremities.
Lepromatous leprosy (M. leprae)
Dermal nodules of granulomatous inflammation. Surrounding skin has loss of pain and sensation.
Tuberculoid leprosy (M. leprae – cell-mediated immunity)
Bilateral bell’s palsy, target-like lesion on skin
Lyme disease
Immigrant from S. America, fever, gray-white patches in throat, sudden peripheral muscle weakness and difficulty breathing.
Diphtheria
Painful, vesicular skin lesions within a band-like pattern on the thorax or face
VZV (shingles)
Most common cause of peripheral neuropathy
What kind of neuropathy is it? What is found on biopsy?
What is the cause?
Diabetes mellitus
Axonal (decreased number of axons)
Abnormal glycosylation of neural tissue, causing destruction
Patient with DM has distal polyneuropathy with numbness, difficulty w/ balance, paresthesias or dysesthesias. What other findings are common (20-40%)? Examples? (3)
Autonomic dysfunctions
- Postural hypotension
- Incomplete bladder empty
- Sexual dysfunction
A patient w/ DM develops neuropathies, some of which are unilateral and asymmetric. What is the cause for these ones?
Microvascular disease, causing ischemia to those particular nerves
Uremia produces what kind of peripheral neuropathy?
Symmetric axonal degeneration
Hypothyroidism causes what kinds of peripheral neuropathy? (2)
Compression neuropathies or distal symmetric sensory neuropathies
Most common toxic cause of peripheral neuropathy?
Alcohol abuse
Most common paraneoplastic form of peripheral neuropathy
What does the damage? To what?
Presentation?
Small cell lung cancer –> sensorimotor neuronopathy
CD8+ T cells on dorsal root ganglion cells
Distal, asymmetric, multifocal neuropathy that progresses
What are paraproteins? Do what?
Distinctive presentation of this?
Monoclonal Ig fragments from neoplastic B cells that bind to neurons and cause immune-mediated demyelination
POEMS syndrome – polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes
Common neuropathies caused by physical forces (trauma or entrapment) (5)
Compression neuropathy Carpal tunnel syndrome Ulnar nerve entrapment Saturday night palsy (Radial) Peroneal nerve
An adult with a peripheral neuropathy. Do NOT rule out an _____ disease
Inherited - often present in adults
Distal LE muscle atrophy, sensory loss, and foot deformities. Leg has “inverted bottle” appearance.
What is it?
Genetics? (3)
Charcot-Marie-Tooth disease
Group of inherited disorders that cause PERONEAL nerve neuropathy.
CMT1 = AD, defective myelin
CMTX = X-linked, defective gap junction in schwann cells
CMT2 = AD, axonal injury due to defective mitochondrial fusion – SEVERE, EARLY
Transient motor and sensory mononeuropathies triggered by compression at common sites of entrapment
Genetics? Causes what finding?
Hereditary neuropathy w/ pressure palsy
PMP22 (same as CMT1) – myelin defect – swollen bulbous myelin sheaths at ends of internodes
Painless weakness of a muscle…think what?
Most common cause?
NMJ impairment
Autoantibodies
Patient experiences progressive muscle weakness over the course of the day, worse with exercise or exertion. Can’t keep her eyes open, and sees double.
Patient is young or middle age. What else to look for?
Relationship between these?
Myasthenia gravis
Thymoma or thymic hyperplasia (B-cell follicles in the thymus)
Thymic disease promotes formation of autoimmunity against acetylcholine receptors on thymic myoid cells
Myasthenia gravis is caused by what?
Autoantibodies against post-synaptic acetylcholine receptors
Patient has weakness of extremities that improves after a few seconds of activity. Dx?
Cause?
What else to look for?
Lambert-Eaton Myasthenic Syndrome
Autoantibodies against presynaptic calcium channels, preventing acetylcholine release
Neuroendocrine (small cell) carcinoma of the lung OR an autoimmune disease (vitiligo, thyroid disease, etc.)
Function of botulinum toxin
Function of curare
Block release of acetylcholine from presynaptic neurons
Block acetylcholine receptors, causing flaccid paralysis
Slow-onset symmetrical proximal muscle weakness and muscle aches. Has trouble getting up from a chair or walking up stairs. Rash around the upper eyelids with edema, or a red scaly rash over joints.
May see what on biopsy of muscle or skin? (2)
See what on labs? (2)
What are those skin rashes called? (2)
May also have what?
Dermatomyositis
- Perifascicular atrophy of muscle fibers
- Deposition of C5-C9 (MAC) within capillary beds
- Elevated CK
- Anti-Mi2/Jo1/P155 autoantibodies
Heliotrope rash (lilac-colored) Gottron papules
Paraneoplastic-producing malignancy
How does polymyositis differ from dermatomyositis? (2)
- No cutaneous features
- No perifascicular atrophy
How does inclusion body myositis differ from polymyositis? (3)
- Late adulthood (65+)
- Quads and distal UE muscles
- cN1A antibody
How to treat inflammatory myopathies?
Corticosteroids
A patient with obesity and hypercholesterolemia is taking a statin to lower his cholesterol. What is the most common complication of this drug?
MYOPATHY (toxic)
Infant presents with severe hypotonia (floppy infant)…what disease class?
Most important genetic? Causes what in infants? (2)
Causes what in adults?
Congenital myopathies
RYR1 (ryanodine receptor) mutation – hypotonia and skeletal abnormalities
MALIGNANT HYPERTHERMIA
Muscular dystrophies present when?
Childhood to adulthood (NOT INFANCY)
Young child (2-5), delayed walking, weakness and atrophy of pelvic muscles. Must place hands on knees to stand up. Labs show normal CK. Dx?
Cause?
Will see what else on observation? Why?
Will find what else on physical exam? (2)
Common causes of death?
Duchenne muscular dystrophy
X-linked frameshift mutation, causing absence of DYSTROPHIN gene
Fibrosis and fatty infiltration of muscle tissue, causing pseudohypertrophy of calf muscles
Cardiomyopathy/arrhythmias and cognitive impairment
Respiratory insufficiency, pulmonary infection, or HF
How does Becker muscular dystrophy differ from Duchenne?
- Later in childhood or adult
- Full life prognosis
- Defective but present dystrophin
- Much less severe
CK levels in muscular dystrophy
What part(s) of muscle is lost?
Elevated in 1st decade of life, then declines as muscle mass is lost
Type 1 AND Type 2 fibers
Sagging face, can’t close mouth, sustained grip or involuntary contraction of muscles
Genetics?
What part(s) of muscle is lost?
Myotonic dystrophy
CTG trinucleotide repeats
Type 1 Fibers ONLY
Slowly progressive humeroperoneal weakness, cardiomyopathy, and early contractures of tendons
EMD1/2 mutation - what proteins?
Emery-Dreifuss Muscualr Dystrophy
Nuclear lamina protein mutations
Prominent weakness of facial muscles and muscles of shoulder girdle. DUX4 over-expression.
Fascioscapulohumeral dystrophy
Patient has episodes of severe muscle cramping and pain after exercise or during fasting. Most likely has a disease associated with defective ____
Severe cases may present with ____
Lipid or glycogen metabolism/storage
Rhabdomyolysis (necrosis)
Patient presents with chronic muscle weakness and elevate serum CK. On PE, extraocular eye muscles appear weak. Must think what kind of disease? Why?
Mitochondrial myopathies
Extraocular muscles have the most mitochondria per mass of any muscle
An infant presents with generalized hypotonia, especially of proximal (thorax) muscles and respiratory muscles. SMN1 mutation is found.
Cause?
Spinal muscular atrophy
Loss of motor neurons
Mutations in ion channels can cause what major clinical manifestations? (5)
- Epilepsy
- Migraine
- Cerebellar dysfunction
- Peripheral nerve disease
- Muscle disease
What is the ryanodine receptor?
2 diseases when dysfunctinal?
Regulator of calcium release from sarcoplasmic reticulum
Congenital myopathy
Malignant hyperthermia
Tachycardia, tachypnea, muscle spasms, hyperpyrexia
Triggered by what?
What causes the symptoms?
Malignant hyperthermia
Halogenated inhalational agents, succinylcholine
Excessive calcium efflux from SR –> tetany and excessive heat production
Well-circumscribed encapsulated mass that abuts a nerve without invading it. Palisading nuclei, Antoni A/B, Verocay bodies.
Most common nerves? (3)
Genetics?
Schwannoma
Vestibular br. of VIII
Branches of V
Branches of dorsal roots
NF2
Mass at the cerebellopontine angle, tinnitus and hearing loss
Common name?
Schwannoma
Acoustic neuroma
Mass of neoplastic Schwann cells, perineural cells, fibroblasts, mast cells, and CD34+ spindle cells
Genetics?
3 types
Bad prognosis?
Neurofibroma
NF1
- Superficial cutaneous (pedunculated nodules)
- Diffuse (large plaque-like)
- Plexiform (w/ nerve roots or large nerves)
PLEXIFORM –> MPNST
Poorly defined, infiltrative mass in the chest, abdomen, pelvis, neck, or limb girdle. Focal areas of random differentiation (glandular, cartilagenous, osseous).
2 types?
Malignant peripheral nerve sheath tumor
- NF1 - from plexiform neurofibroma
- Sporadic (de novo)
Poorly defined, infiltrative mass in the chest, abdomen, pelvis, neck, or limb girdle. Focal areas of rhabdomyoblastic morphology.
Triton tumor (MPNST)
NF1 - tumors (5)
- Neurofibromas
- MPNSTs
- Gliomas of optic nerve
- Glial/hamartomatous tumors
- Pheochromocytoma
NF1 - non-tumor features (4)
- Lisch nodules (pigmented spots on iris)
- Cafe au lait spots
- Mental retardation
- Seizures
NF2 - tumors (3)
- Bilateral 8th nerve schwannomas
- Multiple meningiomas
- Ependymomas of spinal cord
