CNS I Path - Peripheral Nervous System

Question 1

Muscle Biopsy

Answer 1

Make sure to get from the muscle BELLY rather than the junction between the muscle and tendon

Muscle must NOT be fully atrophied, but SHOULD still be actively involved in the pathology

After excision, muscle is SPLIT and rapidly FROZEN with liquid nitrogen to maintain its viability –> need fresh tissue –> don’t put in formalin!!!!!

Question 2

Nerve most commonly used in biopsy?

Answer 2

SURAL NERVE located posterior to the lateral malleolus of the ankle

Question 3

Type 1 and 2 muscle fibers

Answer 3

Type 1 are for SUSTAINED FORCE, weight bearing, slow twitching, and are RED

Type II –> for SUDDEN MOVEMENTS, purposeful motion, fast-twitch and WHITE

Normally there should be a “checkerboard” intermix of muscle fiber types in muscle at any one time – this can be altered in disease so that only one fiber exists, or one massively outweighs the other

Question 4

Nerve Anatomy

Answer 4

Nerve bundles house multiple FASCICLES which each contain several myelinated axons

Epineurium is the outermost collagenous layer of the nerve –> PERIneurium surrounds each fascicle –> ENDOneurium surrounds each individual axon –> and SCHWANN cells myelinate the axons individually

Question 5

How do muscle fibers get innervated

Answer 5

Lower motor neurons innervating a given myocyte will dictate the type of muscle fiber (type 1 or 2) it becomes

Motor unit arising from one LMN will ALWAYS be composed of IDENTICAL muscle fiber types

Question 6

Segmental Demyelination

Answer 6

Inflammatory Disease characterized by injury to random internodes of myelin that are eventually remyelinated by multiple Schwann cells

Clinical presentation of muscle weakness

Myelin will appear THINNER than normal and Schwann cells will be INCORRECTLY circling axons to create an “onion bulb” formation!

Slower conduction of motor signal, but myocytes remain intact

Question 7

Anterograde Wallerian Degeneration

Answer 7

Following insult to a neuron

Since fibers are no longer innervated, they will atrophy (not necessarily die) and accumulate abnormal organelles with loss of myelin around the perimeter

Question 8

Reinnervation

Answer 8

Can occur to atrophied fibers (like in Wallerian degeneration) from nearby, uninjured neurons; if nearby neurons are a diff type (say type 2 instead of type 1) then all the muscle fibers will be of the same type - this is called “fiber type grouping” – loss of checkerboard appearance

Question 9

Guillain Barre Syndrome

Answer 9

Acute, life-threatening immune-mediated disease

Causes inflammation/demyelination of spinal nerve roots and peripheral nerves

Results in ascending muscle paralysis that begins distally and rapidly advances

2/3 preceded by acute, flu-like illness likely associated with C. Jejuni, CMV, EBV or Mycoplasma

Once the body has mounted a response against these pathogens, circulating antibodies and lymphocytes cross-react with neurons

GBS has characteristic clinical presentation and course –> no need for a nerve biopsy

Question 10

Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Answer 10

Subacute or chronic disease that often presents in BOTH limbs (symmetrical)

Sensory and motor functions both implicated, but loss of one may predominate

Nerve biopsy shows demyelination/REMYELINATION and characteristic onion-bulb formation

Not associated with a particular pathogen

Question 11

Leprosy

Answer 11

Lepromatous and TB –> both cause segmental demyelination and remyelination of the SENSORY nerves only

Mycobacterium and granulomatous inflammation in TB form

Question 12

Varicella-Zoster Virus/Shingles

Answer 12

Initial infection in childhood (chickenpox) –> once infected, virus lies DORMANT in the sensory ganglia of the SC and brainstem

IMMUNOCOMPROMISED patients – virus can reactivate, causing PAINFUL vesicular skin lesions following the distribution of a unilateral sensory dermatome

Ganglia show neuronal destruction and loss, accompanied by abundant mononuclear inflammatory infiltrates - no intranuclear inclusions

Question 13

Clostridium Tetani

Answer 13

Usually occurs secondarily to TRAUMA with rusty metal

Spores of the bacteria are injected into tissue where they release their exotoxin –> tetanospasmin (one of the most potent toxins known) –> systemic toxemia

Toxin –> NMJ –> retrograde to motor neuron –> binding gangliosides

Mortality is HIGH

Question 14

Diabetic Neuropathy

Answer 14

Common problem, affecting the majority of patients with Type II DM

Loss of sensation on the bottoms of feet, accompanied by an infected lesion

Nerve biopsy shows loss of small fibers, arteriole thickening, and preservation of large myelinated fibers

Lesion often needs amputation

Question 15

Types of Skeletal Muscle Disorders

Answer 15

Myopathic – Pathogenesis involves an INTRINSIC SKELETAL MUSCLE DISEASE that could be due to genetics, metabolic dysfunction or toxic insult

NEUROPATHIC/NEUROGENIC –> observed changes are due to motor neuron injury/degeneration

INFLAMMATORY –> due to systemic immune system dysfunction or intrinsic muscle disease eliciting an inflammatory response

Question 16

DUSCHENNE MUSCULAR DYSTROPHY

Answer 16

X-linked

Clinically manifests by age 5, weakness leads to wheelchair dependence by age 10-12 and DEATH IN EARLY 20s

Mutations in the DYSTROPHIN GENE are familial in 2/3, de novo in 1/3

MINIMAL DYSTROPHIN PROTEIN

Question 17

Pathology of Duschenne

Answer 17

Variation in fiber size, increased internal nuclei, degeneration/regeneration changes in fibers

Late stages show REPLACEMENT OF MUSCLE BY FAT

Question 18

BECKER MUSCULAR DYSTROPHY

Answer 18

X-Linked

Less severe

DIMINISHED amounts of DYSTROPHIN (not completely absent)

Same pathology as Duschenne –> variation in fiber size, increased nuclei, degeneration/regeneration, replacement of muscle by fat

Question 19

NEMALINE ROD MYOPATHY

Answer 19

Pediatric disease - presents soon after birth

Babies are FLOPPY with minimal muscle tone

Normal Z banding pattern, but Z-material is ABNORMAL with characteristic intracytoplasmic inclusions

Question 20

MITOCHONDRIAL MYOPATHY

Answer 20

Classic finding of RAGGED RED FIBERS!!!!

Mitochondria tend to aggregate along the perimeter of the myofibers, congealing to produce distinct red bands

Mitochondria are LARGE and the cristae begin to line up, producing PARKING LOT INCLUSIONS that alter normal function

Question 21

DERMATOMYOSITIS

Answer 21

Inflammatory disease though to result from SMALL CAPILLARIES leaking in the endomysium causing damage to peripheral myocytes

Affects children and adults, presents with characteristic RASHES

Muscle biopsy –> inflammatory cell aggregates around the muscle and connective tissue producing PERIFASICULAR atrophy (outside of fascicles)

Question 22

POLYMYOSITIS

Answer 22

Inflammatory myopathy affecting SYMMETRICAL, PROXIMAL MUSCLE GROUPS

Necrotic and regenerating muscle fibers are scattered throughout the fascicle with inflammatory infiltrates

ONLY ADULTS

Question 23

INCLUSION BODY MYOSITIS

Answer 23

Involves DISTAL muscles (quads, wrist/ankles)

Often asymmetric

Presence of RIMMED VACUOLES and TUBULAR/FILAMENTOUS inclusions in the cytoplasm and nucleus

Inclusion body myositis affects CHILDREN AND ADULTS

Question 24

STATIN INDUCED MYOPATHY

Answer 24

Myalgia and muscle weakness SECONDARY TO ACTIVE RHABDOMYOLYSIS (necrosis of myoctes)

Mild-moderate serum creatine kinase

Patients need to STOP STATIN THERAPY and it should go away

Question 25

AMYOTROPHIC LATERAL SCLEROSIS

Answer 25

Neurodegenerative disease that implicates BOTH MUSCLES AND NERVES – death of both upper and lower motor neurons!

Causes PROGRESSIVE PARALYSIS that ultimately leads to death in 3-5 years

Highly variable in terms of early symptoms and patterns of progression

Most cases of ALS are SPORADIC - less than 10% familial

Question 26

Clinical Features of ALS

Answer 26

Patients generally present with ATROPHY and WEAKNESS in the HANDS, FEET, LEGS

Fasciculations of the tongue

Upper motor neuron symptoms = Slow speech, brisk gag/jaw jerk, brisk limb reflexes, spasticity, Babinski sign

Lower motor neuron symptoms = Atrophy, fasciculations, weakness

Question 27

Histology of ALS

Answer 27

BUNINA BODIES! Eosinophilic Cystatin-containing inclusions located in the cell body of motor neurons; appear to be remnants of autophagic vacuoles

Presence of TAR-DNA binding protein 43 which may be involved in apoptosis and RNA processing