Hertz peripheral nerves etc. Flashcards
actin and myosin are the gears. What’s the energy?
ATP
workup of nerve stuff
serum chemistries nerve conduction studies muscle biopsy nerve biopsy (sural nerve, innervates sensory portion of the skin by knee) EMG CSF- look at white cells and protein
Charcot Marie-Tooth syndrome
Mutant forms of Myelin Protein Zero (MPZ)
–> demyelinating neruopathy
severe atrophy on one leg, what disease?
poliomyelitis
affects anterior horn (nerve itself)
–> denervation atrophy
what do we see in electron microscopy of demyellinated nerves?
vacuoles
Guillain-Barre
mostly acute-onset immune-mediated demyelinating neuropathy
2/3 of cases are preceded by an acut, influenza-like illness from which the affected individual has recovered by the time the neuropathy becomes symptomatic. Infections with campylobacter jejuni, CMV, Epstein-Barr virus, and mycoplasma pneumoniae, or prior vaccination, have significant epidemiologic associations with Guillain-Barre.
ASCENDING PARALYSIS, won’t see reflexes on achilles tendon, e.g.
blue/ black dots on nerve biopsy?
lymphocytes; immune response causing demyelination
clinical features of guillain barre
ascending paralysis and areflexia
deep tendon reflexes disappear early (can have sensory involvement)
nerve conduction velocities are slowed (multifocal destruction of myelin segments in many axons within a nerve)
CSF protein levels elevated (due to inflammation and altered premeability of the microcirculation within the spinal roots as they traverse the subarachnoid space)
difference between acute and chronic guillain barre
2 months
chronic–> symmetrical mixed sensorimotor polyneuropathy
onion bulb neuropathy
an onion bulb - thinly myelinated axon surrounded by multiple concentrically arranged schwann cells (electron microscopy)
ulnar deviation with big nodes (fingers)
rheumatoid arthritis
neuropathy associated with systemic autoimmune diseases
rheumatoid arthritis
Sjogren syndrome
SLE
can be associated with peripheral neuropathies that often take the form of distal sensory or sensorimotor polyneuropathies
vasculitis
noninfectious inflammation of blood vessels that can involve and damage peripheral nerves
Segmental vasculitidies with “beading”
Polyarteritis nodosum
black dot on skin
kaposi sarcoma (can be nodular too)
papules
= tuberculoid leprosy
bulls eye rash
lyme disease
pseudomembrane back of throat
diptheria
vesicles along a nerve
herpes zoster
most common cause of peripheral neuropathy
diabetes
–> marked loss of myelinated fibers, thickening of endoneurial vessel wall
clinical features of diabetic neuropathy
distal symmetric diabetic polyneuropath- sensory symptoms, numbness, loss of pain sensation, difficulty with balance, paresthesias or dysesthesias
–> increased susceptiibility to foot and ankle fractures and chronic skin ulcers –> amputations
dysfunction of the ANS - protean manifestations, including postural hypotension, incomplete emptying of the bladder (–> recurrent infections), sexual dysfunction
Uremic neuropathy
renal failure –> peripheral neuropathy. Typically this is a distal, symmetric neuropathy that may be asymptomatic or may be associated with muscle cramps, distal dysesthesias, and diminished deep tendon reflexes. In these patients axonal degeneration is the primary event; occasionally there is secondary demyelination. Regeneration and recovery are common after dialysis
Thyroid dysfunction
Hypothyroidism can lead to compression mononeuropathies such as carpal tunnel syndrome or cause a distal symmetric predominantly sensory polyneuropathy. In rare cases, hyperthyroidism is associated with a neuropathy resembling Guillain-Barré syndrome.
Vitamin B12 (cyanocobalamin) deficiency
classically results in subacute combined degeneration with damage to long tracts in the spinal cord, and also peripheral nerves.
Other vitamin deficiencies and peripheral neuropathies
Deficiencies of vitamin B1 (thiamine), vitamin B6 (pyridoxine), folate, vitamin E, copper, and zinc
salty white stuff around mouth is what?
uremic frost
guy in renal failure
bilateral mammillary body hemorrhages is what until proven otherwise?
Wernickes
Toxic Neuropathies
Peripheral neuropathies may appear after exposure to industrial or environmental chemicals, biologic toxins, or therapeutic drugs.
Alcohol (independent of associated nutritional deficiencies), heavy metals (lead, mercury, arsenic, and thallium), and organic solvents. Various medications can cause toxic nerve damage, but the most notorious are chemotherapeutic agents. These include vinca alkaloids and taxanes, microtubule inhibitors that interfere with axonal transport, and cisplatin, which may cause a neuronopathy.
basophilic stippling on blood smear
lead poisoning
spots on hand from
arsenic
Neuropathies Associated with Malignancy
Direct infiltration or compression of peripheral nerves by tumor is a common cause of mononeuropathy and may be a presenting symptom of cancer.
Paraneoplastic neuropathies. These can occur at any time during the patient’s course, but often precede the diagnosis of the underlying tumor. Sensorimotor neuronopathy is the most common paraneoplastic form, but a chronic inflammatory demyelinating polyradiculoneuropathy-like picture, plexopathy, and autonomic neuropathy may also be seen. Paraneoplastic sensorimotor neuronopathy is * most commonly associated with small cell lung cancer.
Neuropathies associated with monoclonal gammopathies. Neoplastic B cells may secrete monoclonal immunoglobulins or immunoglobulin fragments (so-called paraproteins) that damage nerves. For example, tumors that secrete IgM immunoglobulin may be associated with a demyelinating peripheral neuropathy.
example of tumor that grows and –> arm trouble
pancoast tumor - direct extension into brachial plexus
large cells with little cytoplasm
oat cell
clock face nuclei with paranuclear hoff body
multiple myeloma
traumatic neuroma from hitting floor between 2nd and 3rd metatarsal head of foot
morton neuroma
Hereditary motor and sensory neuropathies,
also known as Charcot-Marie-Tooth (CMT) disease
simple—an inherited disease associated with distal muscle atrophy, sensory loss, and foot deformities
congo red stain and peripheral neuropathy
familial amyloid polyneuropathy
Robbins Key concepts peripheral neuropathies
- patterns: mononeuropathy, mononeuritis, pultiplex, polyneuropathy, and polyradiculoneuropathy
- damage may occur in Schwann cells (demyelinating neuropathy), axons, or central neurons, or mixed.
- inflammatory disease, infections, metabolic changes, toxic injury, trauma, paraneoplastic disorders, and inherited gene defects can all –> peripheral neuropathy
- DM most common cause- usually distal symmetric neuropathy
- Guillain Barre and chronic inflammatory demyelinating pollyradiculoneuropathy - major acute and chronic acquired demyelinating peripheral neuropathies
- inherited peripheral neuropathies are genetically and phenotypically diverse disorders, often present in adulthood and may be marked by sensory, motor or autonomic dysfunction, alone or in combo
Diseases of the Neuromuscular Junction
Regardless of cause, disorders that impair the function of neuromuscular junctions tend to present with * painless weakness.
Autoantibodies that inhibit key neuromuscular junction proteins are the most common cause of disrupted neuromuscular transmission, as found in myasthenia gravis (literally, * grave weakness)
Myasthenia Gravis
Myasthenia gravis is an autoimmune disease that is usually associated with autoantibodies directed against acetylcholine receptors.
There is a strong association between pathogenic anti-acetylcholine receptor autoantibodies and * thymic abnormalities.
diplopia and ptosis
myasthenia gravis until proven otherwise
droopy lids plus giant thymus
myasthenia gravis
about 10% of MG patients have thymoma (thymectomy can help); some have thymic hyperplasia
Diagnosis of Myasthenia Gravis
is based on clinical history, physical findings, the * identification of autoantibodies, and electrophysiologic studies. The latter reveal a * decrement in muscle response with repeated stimulation, a characteristic of this disorder.
Lambert-Eaton Myasthenic Syndrome
antibodies that block acetylcholine release by inhibiting a presynaptic calcium channel
- In contrast to myasthenia gravis, rapid repetitive stimulation increases muscle response. Muscle strength is augmented after a few seconds of muscle activity. Patients typically present with weakness of their extremities.
In about half of cases there is an underlying malignancy, most often * neuroendocrine carcinoma of the lung. (CENTRAL tumor) Symptoms may precede the diagnosis of cancer, sometimes by years.
lambert eaton symptoms precede
findings of small cell carcinoma
Botulism
caused by exposure to a neurotoxin (popularly known as Botox) that is produced by the anaerobic Gram-positive organism Clostridium botulinum. Botox acts by blocking the release of acetylcholine from presynaptic neurons.
symptoms: double vission, difficulty swallowing, blurred vision, dry mouth, droopy eyelids, muscle weakness, slurred speech
Curare
common name for botulism related muscle relaxants that block acetylcholine receptors, resulting in flaccid paralysis.
Robbins Key Concepts- NMJ
diseases of NMJ –> painless weakness
Myasthenia gravis and Lambert-eaton myasthenic syndrome (most common forms)- both immune mediated, cuased by antibodies to postsynaptic Ach receptors and presynaptic calcium channels
Myasthenia gravis- often associated with thymic hyperplasia or thymoma, frequently involves ocular muscles, marked by fluctuatin weakness that worsens with exertion
Lambert Eaton- weakness in extremities that improves with repetitive stiulation and often a paraneoplastic disorder associated with lung cancer.
Genetic defects in NMJ proteins–> congenital myasthenic syndrome
Bacterial toxins such as botox can block NMJ by blocking release of Ach from presynaptic neurons
