Disorders of peripheral nerves & the NMJ Flashcards
Peripheral Neuropathies
The term Peripheral Neuropathies is an umbrella term for several specific
types of polyneuropathies and complex mononeuropathies.
Peripheral Neuropathies categories
○ Axonal Neuropathies - Degeneration of the axons/neurons.
■ Speed of conduction is generally normal or mildly slow
○ Demyelinating Neuropathies - Degeneration of the Schwann cells.
■ Speed of conduction is considerably slow, sometimes absent
_____ involve many nerves and generally result
in symmetric symptoms
Polyneuropathies
There are several types of these diffuse polyneuropathies
○ Hereditary (ex: Charcot-Marie-Tooth)
○ Metabolic disorders (ex: Diabetes)
○ Toxic disorders (ex: drugs, pesticides)
○ Guillain-Barre Syndrome
○ Malignancy
Multiple Mononeuropathies (AKA Mononeuropathy
Multiplex) suggests a ______
patchy multifocal disease process
Some causes of Mononeuropathy Multiplex include
○ Vasculopathy (ex: Diabetes, Arteritis)
○ Infiltrative process (ex: Leprosy, Sarcoidosis)
○ Radiation damage
○ Immunologic/inflammatory disorder
Inherited Neuropathies
○ Charcot-Marie-Tooth Disease
○ Dejerine-Sottas Disease
○ Friedreich Ataxia
Neuropathies Associated with Systemic and Metabolic Disorders
○ Diabetic Neuropathy
○ Uremic Neuropathy
○ Neuropathy of Alcoholism
○ Paraproteinemias
Rare inherited condition that results in progressive polyneuropathy
that starts in infancy or childhood
Dejerine-Sottas Disease
Friedreich Ataxia
■ Rare, autosomal recessive disease that causes symptoms to
develop in childhood or early adult life.
■ Characterized by ataxia and other signs of cerebellar dysfunction
Diabetic Neuropathy
Can present in a variety of ways, including complex polyneuropathy or
mononeuropathy multiplex, as a complication of uncontrolled diabetes.
Uremic Neuropathy
Often worse in legs than arms, can improve with transplant or dialysis
Neuropathy of Alcoholism
An axonal polyneuropathy of alcoholism that is often worse in the legs
than arms, often accompanied by painful cramps and tender muscle
Classic example is a polyneuropathy of Multiple Myeloma
Paraproteinemias
Distal polyneuropathy that presents similar to and often in conjunction with neuropathy of alcoholism
Thiamine (Vitamin B1) Deficiency (AKA Beriberi)
Neuropathies Associated with Nutritional Deficiency
○ Vitamin B12 Deficiency
○ Thiamine (Vitamin B1) Deficiency (AKA Beriberi)
○ Pyridoxine (Vitamin B6) Deficiency
○ Niacin (Vitamin B3) Deficiency (AKA Pellagra)
○ Vitamin E Deficiency
Neuropathies Associated with Infectious and Inflammatory Diseases
○ HIV/AIDS
○ Leprosy
○ Lyme Disease
○ Sarcoidosis
○ Rheumatoid Arthritis
Vitamin B12 Deficiency
■ A distal polyneuropathy that is primarily sensory in nature.
■ Often seen with symptoms of anemia, which ends up being a
macrocytic anemia (high MCV on CBC)
Often seen as mild distal sensory polyneuropathy or entrapment
neuropathies, associated with joint inflammation
Neuropathy associated with Rheumatoid Arthritis
Neuropathy Associated with Critical Illness
○ Patients in intensive care units with sepsis and multiorgan failure
sometimes develop axonal polyneuropathies.
○ The pathogenesis is obscure and not well understood.
○ Treatment is supportive and prognosis good if they recover from ICU.
Axonal polyneuropathy may follow exposure to toxic agents:
■ Industrial agents or pesticides
■ Heavy metals (arsenic, mercury, lead, etc.)
■ Drugs (phenytoin, isoniazid, nitrofurantoin, etc.)
■ Diphtheria neurotoxin exposure
Peripheral Neuropathies clinical presentation
○ Patients generally present with some degree of sensory disturbance (“pins and needles,” numbness), motor weakness, or both in the upper and/or lower extremities.
○ Most types are polyneuropathies, which are symmetric and present with a “glove and stocking” distribution
○ Pain is common, generally as a burning, neuropathic pain associated with the “pins and needles.”
○ It’s common to have depressed or absent tendon reflexes in the affected area if it spans over a joint
Peripheral Neuropathies diagnostic workup
■ CBC
■ CMP (especially for renal function and electrolytes)
■ Serum protein electrophoresis
■ TSH
■ Vitamin B12 level
■ Rheumatologic labs (RF, ANA, etc.)
■ Blood glucose and A1C
○ Nerve Conduction Studies and EMG are diagnostic, determines axonal vs
demyelinating neuropathy, and provides a means of following changes
Peripheral Neuropathies treatment
○ When feasible and possible, treating the underlying cause is important.
○ Neuropathic, burning pains or episodic stabbing pains may respond to various medications
■ NSAIDs, such as aspirin, ibuprofen, or naproxen (always with food)
■ Gabapentin or Pregabalin are often effective
■ Duloxetine, Venlafaxine, or TCAs may be helpful, especially in painful diabetic neuropathy
○ Physical therapy helps prevent contractures in severe cases.
○ Splints can help maintain a weak extremity in a position of usefulness.
○ Shoes and soles should be inspected frequently to prevent ulcers
_____ is the most common inherited neuromuscular disorder
CMT Disease (Charcot-Marie-Tooth)
Charcot-Marie-Tooth Disease
● CMT Disease is the most common inherited neuromuscular disorder
● The condition is characterized by
inherited neuropathies without evidence of metabolic derangements
Charcot-Marie-Tooth Disease pathophysiology
○ This group of inherited conditions includes more than 80 gene mutations
○ Several distinct varieties exist, usually with an autosomal dominant mode of inheritance
○ These are sometimes called Hereditary Motor and Sensory
Neuropathies, abbreviated HMSN.
○ There are two main types or categories of CMT:
■ HMSN/CMT Type 1 - Demyelination (slow) on NCS/EMG
■ HMSN/CMT Type 2 - Axonal loss (low amplitude) on NCS/EMG
Pathophysiology and Clinical Presentation of CMT disease
○ Progressive loss of peripheral neuron activity, often starting in childhood, results in muscle weakness, atrophy, and musculoskeletal
deformity of hands and feet due to lack of muscle tone
○ Difficulty walking, frequent tripping,
and a high arched foot (which is
called Pes Cavus).
○ Loss of muscle in distal lower
extremity results in a classic inverted Champagne Bottle sign.
○ A claw hand deformity can occur in the upper extremities
Charcot-Marie-Tooth Disease PE findings
○ Physical exam shows lower
motor neuron signs, positive
Romberg, diminished or absent
reflexes, ataxia, decreased
vibration sensation and
proprioception, and often intact
pain and temperature sensation.
○ Essential tremors are found in
30-50% of cases
Charcot-Marie-Tooth Disease diagnosis
○ If the diagnosis is suspected based on history and physical, NCS/EMG is
the initial diagnostic study of choice.
○ Clinical presentation, possible family history, plus the abnormal
electrodiagnostic studies generally make the diagnosis.
○ Genetic testing is available, evaluating for CMT genetic mutations.
○ Biopsy of the sural nerve is rarely needed, but if performed, will show:
■ CMT Type 1 - Demyelination of the nerve
■ CMT Type 2 - Axonal degeneration of the nerve
Bell Palsy
● Also called idiopathic facial paralysis (IFP), Bell
Palsy is the most common cause of unilateral
facial paralysis
CMT disease treatment
○ There is no cure. No medication slows or reverses the disease course.
○ Goals of therapy are to reduce the symptoms and deformities with a
multidisciplinary approach - Refer to Podiatry, OT, PT, Neurology, Beh Health.
○ Specialized shoe inserts and high-top lace-up shoes are helpful, prescribed by Podiatry.
○ Orthopedic surgery is sometimes performed for musculoskeletal deformities.
○ Daily physical activity is still encouraged and no physical limitations are recommended.
○ Regular and proper follow up is important, as is daily heel stretches to help prevent Achilles contractures
Having ______ increases the risk of
developing Bell Palsy by about 29%
diabetes
Bell Palsy pathophysiology
○ The exact pathophysiology remains an area of debate/disagreement.
○ Sudden onset of lower motor neuron facial palsy.
○ One common theory is that edema and ischemia result as the facial nerve is passing through the facial bones
○ A common theory or possible explanation is that some compression of the nerve occurs in the facial canal around the Stylomastoid Foramen
○ Increasing evidence suggests a reactivation of a virus (HSV or Varicella Zoster), autoimmune attack, or medication adverse reaction
Bell Palsy clinical presentation
○ Unilateral facial weakness (upper and lower
face) comes up abruptly and may worsen over
the first couple of days
○ Pain around the ear and decreased taste
sometimes precedes or accompanies weakness.
○ Hyperacusis can occur due to involvement of
the stapedius nerve fibers.
○ In cases due to Herpes Zoster, vesicles may be observed in the external ear canal
Bell Palsy diangosis
○ Bell Palsy is largely considered a clinical diagnosis.
○ It can be differentiated from a stroke by clinical exam
○ No other neurological abnormalities should be present in Bell Palsy.
○ If other neurologic deficits are present, or facial palsies occur bilaterally,
MRI of the brain should occur and other diagnostics considered.
○ An isolated facial palsy may occur in patients with HIV seropositivity,
sarcoidosis, Lyme disease, and meningitis.
How do you differentiate bells palsy from a stroke?
A stroke or other central lesion generally spares the forehead and eye closure, is usually accompanied by other focal deficits, and will
not cause hyperacusis or disturbance of taste.
Bell Palsy treatment
○ Approximately 60% of cases will recover completely without treatment.
○ Treatment with Prednisone or Prednisolone has been shown to increase chances
of a complete recovery at 9-12 months by 12-15%.
○ Treatment with Acyclovir or Valacyclovir is indicated when there is evidence of
herpetic vesicles in the external ear canal.
○ Eye care is important for almost all patients
Trigeminal Neuralgia
● Also known as Tic Douloureux, meaning painful tic, is a distinct facial pain
syndrome that can cause a lot of anguish and suffering for patients
● While it can be an acute problem for some
people, for others, it becomes a chronic and
recurrent pain.
● It is most common in middle and later life,
and is uncommon in younger individuals.
● It seems to affect females more frequently
than males, although there’s no proven
explanation for this
Trigeminal Neuralgia pathophysiology
○ The exact pathophysiology is not always clear.
○ Sometimes vascular compression or irritation of the trigeminal nerve near its exit from the Pons is the underlying problem
○ Not everyone with Trigeminal Neuralgia
has this vascular compression near the
pons, so there are likely multiple causes.
○ Viral infection and autoimmune attack
have been theorized as possible
explanations
Trigeminal Neuralgia clinical presentation
○ Momentary episodes of sudden lancinating facial pain, commonly
arising near one side of the mouth and shooting toward the ear, eye, or
nostril on that side.
○ The pain may be triggered by touch, movement, drafts, and eating
○ Symptoms remain confined to the distribution of the trigeminal nerve
(usually the second or third division) on one side only.
Trigeminal Neuralgia diagnosis
○ Trigeminal Neuralgia is considered a clinical diagnosis, based on the
patient’s history and a normal physical exam.
○ No labs or imaging are necessary unless other conditions are suspected.
○ If history or physical suggests another diagnosis, an MRI of the brain is
the initial imaging modality of choice.
○ Multiple Sclerosis must be suspected in patients under the age of 40,
even if classic Trigeminal Neuralgia is the only concern.
Trigeminal Neuralgia treatment
■ First-line agents are Carbamazepine or Oxcarbazepine.
■ A second-line agent would be Phenytoin.
■ Baclofen, Topiramate, Lamotrigine, or Gabapentin may also be
helpful, either alone or in combo with any of these other agents
○ In cases where vascular impingement is the suspected cause,
neurosurgery can perform a Microvascular Decompression of the nerve.
○ If medical management fails, the patient may elect for a Rhizotomy,
which is easy, has few complications, and provides great pain relief
Complex Regional Pain Syndrome
● Formerly called Reflex Sympathetic Dystrophy, CRPS is a pain syndrome
that can develop, usually in an extremity, following an injury or surgery
● The pain is sharp and neuropathic in nature, but the syndrome presents with
more than just pain in the recently injured extremity
Complex Regional Pain Syndrome pathophysiology
○ The current theory of experts is that CRPS develops when persistent
noxious stimuli from an injured body region leads to peripheral and
central sensitization, meaning the primary afferent nociceptive fibers
demonstrate abnormally extreme sensation, including spontaneous pain
and hyperalgesia
○ This all seems to cause the skin in the injured area to become more
sensitive to all stimuli, even stimuli that shouldn’t be painful
Complex Regional Pain Syndrome clinical presentation
○ Characteristic signs and symptoms are pain
localized to an arm or leg, swelling of the
involved extremity, disturbances of color and
temperature in the affected limb, limited range
of motion, and dystrophic changes to the
overlying skin and nails
○ Pain is often burning in quality and greatly worsened with minimal stimuli.
○ Motor function impairment is seen in about 80% of patients.
○ Some may experience abnormal sweating in the area too
Complex Regional Pain Syndrome diagnosis
○ CRPS is largely a clinical diagnosis, one of exclusion.
○ If Compartment Syndrome is possible, intracompartmental pressure may need to be measured - would be normal in CRPS
○ Bone Scans are sensitive in early stages of the disease, showing an increased uptake in the affected extremity
Complex Regional Pain Syndrome management
○ Early mobilization after an injury or surgery reduces the likelihood of developing
the syndrome
○ Physical Therapy plays a major role in pain management and efforts to restore
function of the affected limb.
○ For mild cases, NSAIDs (like Naproxen) can be effective.
○ For more severe cases associated with edema, a large round of Prednisone may
be effective (high for 2 weeks, then tapered over two weeks).
○ Helpful adjunct treatments can include TCAs, Gabapentin, or a Lidocaine patch.
○ Use of opioids for pain management is not recommended.
Myasthenia Gravis
● MG is a relatively rare autoimmune disorder,
with an annual American incidence of 2 cases
per 1,000,000 people.
● The condition is well-known to be
autoimmune and we consider it to be an
idiopathic disease with no known trigger
● The condition can occur at any age.
○ Incidence peaks in the third decade of life
for females, and in the sixth and seventh
decade of life for males
Myasthenia Gravis pathophysiology
○ In MG, the body inappropriately forms antibodies against acetylcholine nicotinic postsynaptic receptors at the neuromuscular junction.
○ When the receptors are bound by an antibody in the synaptic cleft, Acetylcholine is unable to bind, which prevents normal depolarization of the muscle
Myasthenia Gravis presentation
○ Patients characteristically present
with ptosis, diplopia, difficulty chewing or swallowing, respiratory difficulties, limb weakness, or some combination of these problems
○ Symptoms often fluctuate in intensity during the day and increased activity often increases the level of weakness.
■ Resting can allow for symptoms to decrease again
○ Extraoccular muscles are involved in most cases, which means ptosis and ocular
palsies are classic and often asymmetric
○ The disorder follows a slowly progressive
course in most cases.
○ May have a fatal outcome secondary to
respiratory complications, such as
aspiration pneumonia.
○ Life-threatening exacerbations of
myasthenia are called Myasthenia Crisis
Myasthenia Gravis diagnosis
○ Serum antibody testing for Anti-Acetylcholine Receptor Antibodies is useful because it has a sensitivity of 80-90% for diagnosing MG
○ About half of the patients with seronegative MG may have antibodies to muscle-specific tyrosine kinase (MuSK).
○ Anti-Striated Muscle (anti-SM) Antibody testing should be performed as well, as it is positive in about 84% of patients with an associated thymoma (thymomas occur in about 15% of those with MG)
Myasthenia Gravis management
○ All patient should be referred to a Neurologist as treatment requires a close specialist-patient relationship
○ Treatment of choice is an Acetylcholinesterase Inhibitor, which prevents the breakdown of Acetylcholine, which increases its presence in the synaptic cleft.
○ If a thymoma is discovered, it should be
removed - Thymectomy.
○ Treatment with a corticosteroid is indicated in patients who have
responded poorly to Acetylcholinesterase Inhibitors
○ Patients presenting with acute exacerbation and/or respiratory difficulty
should be admitted for treatment of Myasthenia Crisis.
■ Should be treated with IVIG or Plasmapheresis
