Systems Pathology I - Exam 2 (Peripheral Nervous System)

What are 3 key features of motor units?

1) Lower motor neuron/peripheral axon

2) Neuromuscular junction

3) Innervated myocytes

NOTE: There can be a problem at any one of these locations

What are some key differences between PNS damage (Anterior horn of spinal cord & peripheral nerves) and CNS damage (Brain)? (4)

PNS

-- LMN

-- muscle weakness (flaccidity)

-- Decreased DTRs (deep tendon reflex; stretch reflex)

-- Sensory loss common

CNS

-- UMN

-- Muscle weakness (spasticity)

-- Increased DTRs (deep tendon reflex; stretch reflex)

-- MAY include sensory loss but not necessarily

What are the two primary patterns of Peripheral nerve injury?

1) Axonal neuropathy

2) Demyelinating neuropathy

What is a test that is able to detect a loss of AMPLITUDE (signal strength) and/or a loss of VELOCITY (conduction speed)?

NCV Test

(Nerve Conduction Velocity Test)

NOTE: Don't forget this is testing for amplitude & velocity; not just velocity like name implies

In the Seddon Classification for Peripheral Nerve injury classification, which injury is a mild compression/traction injury that is temporary (good recovery) because the axon is still intact?

Neuropraxia

In the Seddon Classification for Peripheral Nerve injury classification, which injury is a moderately severe injury where the axon is severed, but the endo, peri, and epineurium is intact with regeneration expected 1mm/day?

Axonotmesis

In the Seddon Classification for Peripheral Nerve injury classification, which injury is a severe injury where the nerve is completely severed and there is poor regeneration capacity?

Neurotmesis

What is direct injury to a peripheral axon that involves degeneration of the distal portion of the axon, and eventually the associated myelin will also degenerate?

Axonal Neuropathy

What describes the fragmentation of the axon and myelin that occurs distal to the area of the injured axon in axonal neuropathy?

Wallerian degeneration

In axonal neuropathy, regrowth/remyelination is possible, but the repaired peripheral neuron manifests with what 2 characteristics?

1) Decreased axon density

2) Decreased amplitude on NCV test

What is injury to Schwann cells or the myelin sheath, but the axonal processes are spared from injury?

Demyelinating Neuropathy

When demyelinating neuropathies causes discontinuous (random) internode demyelination, what is it called?

Segmental demyelination

In Demyelinating neuropathy, repair is possible, but it results in what 2 characteristic changes?

1) Thin myelin sheaths & Shortened internodes (altered structure)

2) Slow conduction velocity of NCV

What is damage to an individual nerve (ONE), most likely to manifest with isolated motor or sensory deficits and are commonly the result of traumatic injury to a peripheral nerve? What are two examples?

Mononeuropathy

Examples:

- Entraptment --> carpal tunnel syndrome

- Trauma --> shoulder dislocation --> Axillary nerve palsy

What is damage to multiple nerves, which characteristically manifests with diffuse and symmetrical sensory or motor defects, most likey affecting longest axons in the body? What are some things that can cause this?

Polyneuropathy

-- Causes = Diabetes, alcoholism, lead

What type of appearance is most characteristic of polyneuropathy since the most distal areas are affected first?

Stocking-and-glove paresthesia

What is an immune-mediated condition that causes acute demyelination and primary affects the motor neurons in the lower extremity with sudden (acute) onset of lower extremity weakness and lack of stability while standing/walking?

Guillain-Barre syndrome (GBS)

What is a classical presentation of GBS with ascending weakness and individuals describing sensation of having "rubbery legs"? If left untreated, what can it progress to?

Ascending paralysis (leg weakness)

-- Respiratory failure

Who is most affected by Guillain-Barre syndrome?

Males

15-35 OR 50-60

NOTE: this one not a big testable one since not very reliable

Why does GBS occur? Is it idiopathic?

60% idiopathic

-- macrophages near nerve roots, so indicative of some infection such as C. jejuni, EBV, CMV, HIV, Zika

-- this is an autoimmune cross reactivity following exposure to an infection (typically from food poisoning)

What is the treatment for Guillain-Barre syndrome?

Most cases self resolve (90%)

-- but treatment can be ventilation, plasmapheresis, and IV antibodies

What is a chronic immune-mediated relapsing demyelinating/remyelination disorder that causes sensory and motor (sensorimotor) neuropathies, leading to insidious onset of muscle weakness, pain, ataxia, and decreased deep tendon reflex? How long does this persist?

Chronic Inflammatory Demyelinating Polyneuropathy

(CIDP; Chronic GBS)

-- persists for atleast 2 months

What is a characteristic chronic feature of the myelin injury in CIDP (Chronic Inflammatory Demyelinating Polyneuropathy; Chronic GBS)?

Schwann cells that resemble "onion bulbs" on a biopsy

Who (age/gender) is most commonly affected by CIDP?

Males (2x)

40-60 years

(Older males 40+)

What is a risk factor for developing Chronic GBS?

History of SLE (systemic lupus erythematosus) or HIV

-- idiopathic

What is the treatment for Chronic Inflammatory Demyelinating Polyneuropathy? What is the prognosis?

Plasmapheresis and Immunosuppression

-- possible recovery, but typically some residual loss of function

What is the metabolic disorder characterized by prolonged periods of hyperglycemia (high blood sugar)?

Diabetes mellitus

(Type I, Type II, gestational diabetes)

What are the small arteries that supply blood and nutrients to peripheral neurons?

Vasa nevorum

What is a mixed (axonal & demyelinating) polyneuropathy nerve damage pathology in patients with long-term diabetes mellitus due to microvascular injury (vasa nervorum) which leads to nerve injury, beginning with decreased sensation and can lead to ulcers, gangrene, intense burning, and decreased DTRs? How common is this?

Diabetic Peripheral Neuropathy

-- most common form of peripheral neuropathy

What is the treatment of Diabetic Peripheral Neuropathy?

glucose control

-- daily inspection

-- analgesics & anticonvulsants

What part of the nervous system are most susceptible to damage in patients with diabetic neuropathy?

Longest axons in body (those supplying toes and fingers greatest risk)

What is a damaging effect that can be a result of diabetic peripheral neuropathy to the retina? What are some symptoms?

Diabetic retinopathy

--> vision problems, possible blindness

What is a damaging effect that can be a result of diabetic peripheral neuropathy to the kidney? What is a symptom?

Diabetic nephropathy

--> glomerulonephritis

What pathology is characterized by progressive joint destruction, dislocations, and pathogenic fractures following an neuropathy (possible complication) that involves reduced lower extremity joint sensation due to numbness and lack of circulation?

Neuropathic Arthropathy

(Charcot joint, neuropathic joint)

What is the most common cause of Neuropathic Arthropathy? What are some other causes?

MC = Diabetes mellitus

Others = spinal cord injury, syphilis, leprosy

What joints are most commonly affected by Neuropathic Arthropathy?

Foot, ankle, hip, tarsometatarsal & metatarsophalangeal joints

What is a common characteristic visual feature of Neuropathic Arthropathy?

Edema & joint destruction; pressure ulcers

What are some toxic environmental exposures that disrupt axonal transports or cytoskeletal structure? What nerves are more commonly affected?

ADRs (Adverse drug reaction), Chemotherapy, lead, methylmercury, heavy metals

-- affects longest neurons

What miscellaneous peripheral nerve injury affects motor and sensory nerves, involving inflammation and injury/ischemia of peripheral nerves and commonly seen in polyarteritis nodosa, SLE, RA? What is a characteristic feature?

Systemic Vasculitis

-- mononeuritis multiplex = asymmetric & patchy

What is a related group of inherited neuropathies with axonal or demyelinating neuropathy, damaging motor & sensory neurons, and involves a PMP22 mutation?

Charcot-Marie-Tooth Disease

NOTE: INHERITED

What nerve is most commonly affected by Charcot-Marie-Tooth Disease? What is a characteristic appearance of this condition due to this nerve affected?

Deep fibular nerve

-- results in decreased dorsiflexion which results in "steppage-gait"

NOTE: Deep fibular nerve innervates the tibialis anterior, extensor digitorum longus, and fibularis muscles

Who is most commonly affected by Charcot-Marie-Tooth Disease?

Manifests in young adults (MC) that have inherited associated myelin defect genes

What is a unique radiographic appearance of Charcot-Marie-Tooth Disease?

Pes cavus

What is the autoimmune condition involving antibodies against an individuals own postsynaptic acetylcholine (ACh) receptors, inhibiting myocyte depolarization and causing painless muscle weakness and causing extraocular weakness (ptosis & diplopia) and may progress to descending paralysis?

Myasthenia Gravis

In Myasthenia Gravis, ______% is due to thymic hyperplasia and ____% due to thymoma since its an autoreactive T cell & B cell condition (antibody mediated)?

60%

20%

NOTE: it's a type II hypersensitivity; worse with stimulation

Who is most commonly affected by Myasthenia Gravis?

Females most commonly

(20-30)

Males can also be affected but more in 50-70 age range

What is a distinctive characteristic of myasthenia gravis symptoms (in general)?

They worsen as the day progresses (fluctuating features)

What is the acetylcholinesterase inhibitor that improves symptoms for Myasthenia gravis?

Tensilon test (edrophonium)

What is the treatment of Myasthenia Gravis? What is the prognosis?

Thymectomy, acetylcholinesterase inhibitor meds, immunosuppression, plasmapheresis

-- 95% have 5-year survival

What is an autoimmune condition involving the formation of antibodies against one's own presynaptic calcium ion channels, inhibiting the release of ACh in the neuromuscular junction, preventing myocyte depolarization and causing myasthenia?

Lambert-Eaton Syndrome

Who is most affected by Lambert-Eaton Syndrome?

60+

What are two treatments for Lambert-Eaton Syndrome? What is another therapy that can improve both Myasthenia Gravis & Lambert-Eaton Syndrome?

Plasmapheresis & immunosuppression

-- therapy = e-stimulation

What is the paraneoplastic syndrome that can cause a poor prognosis for those with Lambert-Eaton Syndrome?

Small cell lung cancer

What condition is the increased stimulation of skeletal muscle & spasm ("lockjaw"), that may lead to lethal respiratory failure (10%)?

Tetanus

How does Tetanus spread? What does it do to the body/what neurotransmitter does it affect?

Bacteria = Clostridium tetani (found in contaminated soil)

-- Toxin travels towards CNS in peripheral neurons to BLOCK release of inhibitory neurotransmitter (GABA), and decreases inhibition of alpha motor neurons on anterior horn

Who is most affected by tetanus? What is the incubation period?

Anyone exposed

-- puncture wound with contaminated soil/object which will incubate for 10 days

What is the condition characterized by muscle flaccidity (flaccid paralysis), characterized by being present in contaminated soil, bee honey, or improper canned food items and can lead to descending paralysis affecting cranial nerves and progressing to diaphragm? What bacteria causes this?

Botulism

-- Clostridium botulinum

When botulism paralysis affects the cranial nerves first, what is it called? What is botulism called when it has progressed to the diaphragm?

CN == Bulbar palsy

Diaphragm = Descending paralysis

If an infant develops botulism, for example if an infant eats honey in the first 12 months of life, what is it called?

Floppy Infant Syndrome

Infant Botulism

How does Botulism cause the muscle flaccid paralysis/inhibition?

Inhibits ACh release by alpha motor neuron presynaptic terminal

Who is most at risk for Botulism?

Anyone w/ sufficient exposure to toxin (especially newborns due to underdeveloped gut flora)

What is the therapeutic for muscle dystonia/hypertonicity which is a refined version of botulism?

Botox

Skeletal muscle tissue is composed to what two motor neurons that determine the myofiber types?

Type I & Type II

Which of the two primary muscle types (motor neurons) is fast twitch, anaerobic, and involves glycogen?

Type II

Which of the two primary muscle types (motor neurons) is slow twitch, aerobic, and involves fat?

Type I

Peripheral axons innervate multiple myocytes, with the muscle fiber types being intermixed in a _____________ pattern.

Checkerboard

What is the primary disease of muscle?

Myopathy

What is painless muscle weakness?

Myasthenia

What type of changes are most likely to cause segmental necrosis and regeneration of individual muscle fibers?

Myopathic changes

What type of changes are most likely to cause grouped atrophy and fiber type grouping, losing the normal "checkerboard" pattern of muscle fibers and resulting in larger but fewer motor units?

Neuropathic changes

Both neuropathies and myopathies involve what 3 symptoms? Which is involved when the neuropathy/myopathy is chronic?

1) Atrophy

2) Myasthenia

3) Fibrofatty replacement --> CHRONIC

What type of skeletal muscle disorders follows prolonged disuse of skeletal muscle tissue and primary involve atrophy of type II fibers?

Disuse atrophy

What is an example of a cause of LOCALIZED Disuse atrophy? GENERALIZED Disuse atrophy?

Localized = Fracture (casting)

Generalized = Quadriplegia

What type of skeletal muscle disorder may develop in patients with elevated glucocorticoid (corticosteroid; hypercortisolism) levels, and is most likely to cause atrophy of type II muscle fibers?

Glucocorticoid atrophy

What endocrine disorder is defined by the presence of hypercortisolism (elevated blood cortisol) involving the atrophy of skeletal muscle tissue within the extremities due to glucocorticoid atrophy, and has symptoms including weight gain (moon phase, purple straie, buffalo hump), hirsutism, insomnia, and infertility?

Cushing syndrome

What are two causes of Cushing Syndrome and which is most common?

1) Exogenous corticosteroids (MC)

2) Adenoma (pituitary or adrenal) = increase ACTH --> (Cushing Disease)

Who is most commonly affected by Cushing syndrome?

Females

Young adults

What is a group of inherited myopathies that interfere with the production of proteins needed to produce and maintain healthy muscle mass?

Muscular Dystrophy

What is a form of muscular dystrophy that result form X linked mutations in dystrophin gene (DMD gene located on Xp21), coding for dystrophin protein and causing segmental necrosis of myocytes, and elevate kinase levels in the blood?

Dystrophinopathies

What is dystrophin's function? What occurs if this is absent?

Stabilize muscle fibers during contraction

-- if absent, muslces have reduced stiffness, more prone to tearing, and overall stability reduced

What are some shared features of Dystorphinopathies? (5) Do they all have the same severity?

Variable severity, but share features

1-- clumsiness, weakness, fatigue

2-- pelvic girdle weakness (shoulder when advanced)

3-- pseudohypertrophy of calf muscles

4-- cardiorespiratory insufficiency (cardiomyopathy, arrhythmia, pneumonia)

5-- increased creatine kinase

T/F: Myocyte degeneration in Muscular Dystrophy outpaces repair.

TRUE

What is an inherited myopathy condition due to ABSENT dystrophin protein with progressive & ultimately fata muscle weakness of skeletal & cardiac muscle, beginning in childhood with proximal muscle weakness (gower sign) and FATAL in teens/early adulthood?

Duchenne Muscular Dystrophy

What is the Gower sign in Duchenne Muscular Dystrophy?

Using hands to push on legs to stand

-- due to the calf pseudohypertrophy

How does Duchenne Muscular Dystrophy arise?

Absent dystrophin protein DECREASES structural integrity of myocytes and leads to progressive destruction and weakness

Who is most affected by Duchenne Muscular Dystrophy? Why?

Boys

(X-linked inheritance)

(1 in 3,500)

What is the inherited myopathy condition due to mutated (ABNORMAL) dystrophin protein, demonstrating proximal weakness, but does have the possibility of having a normal life span?

Becker Muscular Dystrophy

T/F: Duchenne Muscular dystrophy is more severe than Becker Muscular Dystrophy.

TRUE

How does Becker Muscular Dystrophy arise?

Mutated dystrophin protein = increased breakdown of muscle

Who is most affected by Becker Muscular Dystrophy? Why?

Boys in adolescence or adults

(X-linked inheritance)

(1 in 30,000)

What is a common first manifestation of thyrotoxicosis (elevated thyroid hormones, hyperthyroidism) and commonly manifests with muscle weakness (necrosis of proximal muscle)? Is this acute or chronic?

Thyrotoxic Myopathy

(Can be either acute or chronic)

What condition may develop following episodes of binge drinking, causing acute myalgia, myocyte swelling/necrosis (rhabdomyolysis), and in as a severe consequence, acute renal failure?

Ethanol Myopathy

What condition may develop following exposure to a variety of medications (adverse drug reaction - ADR), having myopathic sings/symptoms but usually without inflammation?

Drug Myopathy

What are the two types of Drug Myopathy? Which is more common?

1) Statins myopathy --> myalgia & cramps

(MOST COMMON)

2) Chloroquine

What is an autoimmune reaction directed against thyroid-stimulating hormone receptors (TSH) and is the most common cause of thyrotoxicosis (elevated T3 & T4), and causing thyromegaly (goiter), weight loss, fatigue, insomnia, exophathalmoses, pretibial myxedema, and rapid/irregular heartbeat?

Graves' Disease

Who is most likely to develop Graves' Disease?

Females

What are a group of benign or malignant tumors that manifest with Schwann cell differentiation, most common to develop during adulthood and are relatively soft and painless leasions?

Peripheral Nerve Sheath Tumors

What is the benign encapsulated peripheral nerve sheath tumor that develop form transformed Schwann cells often sporadic and may compress CN VIII or other cranial nerves, leading to hearing loss, tinnitus, or vestibular dysfunction?

Schwannoma

(Acoustic neuroma)

(vestibular schwannoma = when on CN VIII (vestibulocochlear nerve))

Who is most affected by Schwannoma? Why?

50+

(Idiopathic)

What is characterized by multiple benign schwannomas throughout the body (CNS & cutaneous) and is familial (or idiopathic), but does not have vestibular schwannomas, as it is NOT associated with cranial nerves?

Schwannomatosis