Peripheral Nerve and Skeletal Muscle Path

Question 1

Segmental Neuropathy

Etiologies (2) Unaffected Structures (2) Characteristic Morphology (1)

Answer 1

Schwann cell dysfunction
Direct damage to myelin sheath

Axon and Myocytes untouched

Onion bulb concentric layers of Schwann cytoplasm

Question 2

Axonal Neuropathies

Morphology (2) Complication with Description (2)

Answer 2

Wallerian degeneration
Myelin ovoids (degrading myelin sheath)

Traumatic neuroma
Painful pseudotumor
Disordered orientation of regrowing axons

Question 3

Nerve Regeneration and Muscle Reinnervation Process
Early Compensation (2) Muscle Typing

Answer 3

Unaffected axons reinnervate denervated myocytes
Form new motor unit, adhering to type grouping

Motor neuron determines type of muscle fiber

Question 4

Muscle Fiber Atrophy
Etiologies (4) Morphology (2)
Reactions (2) with Descriptions (2/1)
Regeneration Characteristics (3)

Answer 4

Denervation (group atrophy)
Neurodegenerative diseases
Inactivity
Glucocorticoid therapy

Angulated Fibers
Target Fibers

Segmental necrosis: myophagocytosis followed by collagen and fat deposition

Hypertrophy: muscle fiber splitting

Regeneration:
Red cytoplasm
Central nuclei
Stains basophilic

Question 5

Mononeuritis Multiplex

Etiologies (2) Description

Answer 5

Vasculitis (polyarteritis nodosa)
HIV

Nerves damaged in haphazard fashion

Question 6

Peripheral Nerve Damage
Common Symptom
Anatomic Variants with Descriptions
Mono (1) Poly (3) Polyradiculo (2)

Answer 6

Pins and needles pain

Mononeuropathy affects single nerve

Polyneuropathy: multiple nerves
Symmetric Ascending symptomology
Glove and stocking distribution

Polyradiculoneuropathy: multiple nerves and nerve roots
Symmetric proximal and distal symptomology

Question 7

Bell’s Palsy

Etiology, Associations (2) Presentation

Answer 7

CN VII mononeuropathy

Upper respiratory infection
Diabetes mellitus

One sided face droop

Question 8

Neurogenic Bladder
Disease Associations (4)

Answer 8

Multiple sclerosis
Parkinson’s Disease
Spina Bifida
Diabetes

Question 9

Guillain-Barre Syndrome

Etiologies (2) Pathogenesis (2) Morphology (4) Presentation (2) CSF Finding (1) Treatment (2)

Answer 9

Influenza-like illness
Campylobacter jejuni

Anti-myelin Abs
Macrophages attack Schwann cells at nodes of ranvier

Perivenular and endoneurial inflammatory infiltrate
Segmental demyelination of nerves and nerve roots

Ascending paralysis starting in distal LE
Loss of DTR’s

Elevated Protein in CSF

Plasmapharesis
IV Ig

Question 10

Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Clinical Features (3) Morphology

Answer 10

Symmetrical mixed sensorimotor neuropathy
Lasts > 2 months
Responsive to corticosteroids

Onion bulb Schwann cells

Question 11

Leprosy

Pathogenesis (3) Morphology (2) Clinical Features (3) Staining (1)

Answer 11

Schwann cells invaded by Mycobacterium leprae
Segmental demyelination/remyelination
Loss of myelinated and unmyelinated axons

Endoneurial fibrosis
Thickened perineural sheaths

Symmetrical polyneuropathy of cool extremities
Loss of pain sensation
Large traumatic ulcers

(+) AFB staining

Question 12

Diphtheria

Pathogenesis (3) Clinical Features (3)

Answer 12

Exotoxin mediated
Selective demyelination of axons going to anterior/posterior root and sensorimotor nerves

Early paresthesias and weakness
Bulbar and respiratory dysfunction
Tonsillar exudate

Question 13

Diabetic Peripheral Neuropathy

Pathogenesis (3) Morphology (3) Clinical Features (4)

Answer 13

Segmental demyelination
Loss of small myelinated fibers and unmyelinated fibers
Decreased axons

Thickened, hyalinized, PAS (+) endoneurial arterioles

Ascending distal symmetric sensorimotor polyneuropathy
Paresthesias
Dysthesias
Autonomic Dysfunction (postural hypotension)

Question 14

Uremic Neuropathy

Etiology and Clinical Features (2)

Answer 14

Renal failure

Distal symmetric neuropathy
Healed by dialysis

Question 15

Thyroid Associated Neuropathy

Hyper (1) Hypo (2)

Answer 15

Hyperthyroidism causes Guillain-Barre-like syndrome

Hypothyroidism causes compression neuropathies
Carpal tunnel

Question 16

Malignant Neuropathies
Paraneoplastic (2)
B cell Neoplasms: Pathogenesis, Presentation (5)

Answer 16

Sensorimotor paraneoplastic syndrome
Small cell lung carcinoma

B Cell Neoplasms:
Deposition of paraprotien between noncompacted myelin lamellae
POEMS: polyneuropathy, organomegaly, endocrinopathy, Monoclonal gammopathies, skin changes

Question 17

Compression Neuropathies
Syndromes (3) with Entrapped Nerve
Other Commonly Entrapped Nerves (2)

Answer 17

Carpal Tunnel: Median N

Saturday Night Palsy: Radial N

Morton Neuroma (metatarsalgia): Interdigital N

Ulnar N
Peroneal N

Question 18

Charcot-Marie Tooth

Genetics (3) Presentation (2)

Answer 18

Autosomal Dominant
Chr 22 mutation
PMP22 defect

Slowly progressive demyelination starting in second decade

Question 19

Myasthenia Gravis

Etiology, Clinical Features (5) Treatments (3)

Answer 19

Ach receptor autoantibodies

Diplopia
Ptosis
Worsened by activity, repeated stimulation
Thymic Hyperplasia (B cells on histo)
Thymoma

Acetylcholinesterase inhibitors
Immunosuppression or plasmapharesis
Thymectomy

Question 20

Lambert Eaton Syndrome

Etiology, Pathogenesis (2) Presentation (2)

Answer 20

Paraneoplastic syndrome of small cell lung carcinoma

Autoantibody to Ca2+ channel
Blocks acetylcholine release

Proximal muscle weakness
Improved by activity, repeated stimulation

Question 21

Muscle Fiber Type Characteristics
Action, Activity Type, Specialization
Type I, Type II

Answer 21

Type I:
Sustained force
Aerobic exercise
High resistance to fatigue

Type II:
Fast movement
Anaerobic exercise
High power production

Question 22

Dermatomyositis

AutoAbs (3) Morphology (3) Clinical Features (3) Histology, Complications (4)

Answer 22

anti-Mi2
anti-Jo1
anti-P155/P140

Upper eyelid rash* (lilac/heliotrope/violet)
Telangiectasias causing rash and periorbital edema
Grotton lesions: scaly, on knuckle/elbows/knees

Proximal muscle weakness (trouble walking up stairs)
Dysphagia
Interstitial lung disease

Perifascicular atrophy*

Visceral cancer
GI ulcers (juvenile)
Calcinosis (juvenile)
Lipodystrophy (juvenile)

Question 23

Polymyositis

Pathogenesis, Morphology(2) Clinical Features (3)

Answer 23

CD8+ T cell mediated inflammation (mononuclear infiltrate)

Endomysial inflammation*
Random fiber atrophy*

Adult onset
Myalgias
Proximal limb weakness

Question 24

Inclusion Body Myositis
Clinical Features (3) Morphology

Answer 24

Slow progressive muscle weakness
Quadriceps and Distal Upper Extremities most affected
Dysphagia

Rimmed vacuole inclusions

Question 25

Toxic Myopathies | Examples (5) with Descriptions

Answer 25

Statins Chloroquine and Hydroxychloroquine Corticosteroids Thyrotoxic: proximal muscle weakness Alcohol: Rhabdomyolysis, renal failure

Question 26

X Linked Muscular Dystrophies Common Genetic Defect and Common Morphology Duchenne Features (3) Becker Features (3)

Answer 26

Xp21 gene mutation Pseudohypertrophy: muscle replaced with Adipose, CT Duchenne: Dystrophin absent Early symptoms and wheelchair bound by 10 years Females are carriers Becker: Dystrophin decreased Normal lifespan Cardiac disease

Question 27

Myotonic Dystrophy | Genetics (3) Clinical Description (2) Symptoms (5) Morphology

Answer 27

Autosomal dominant CTG repeat DMPK defect Sustained involuntary contraction of muscles Myotonia elicited by percussion of thenar eminence ``` Ptosis Hatchet face Cataracts Endocrinopathy Cardiomyopathy ``` Ring fibers

Question 28

Emery Dreifuss Syndrome | Genetics (2) Clinical Triad

Answer 28

X linked: EMD1 Autosomal Dominant: EMD2 Slowly progressive weakness Cardiomyopathy Early contractures

Question 29

``` Lipid/Glycogen Metabolism Defects Common Symptomology (2) Examples with Defects (3) ```

Answer 29

Slowly progressive muscle damage Symptoms show with exercise and fasting Carnitine Palmitoyltransferase II deficiency McArdle Disease: myophosphorylase deficiency Pompe Disease: Acid Maltase deficiency

Question 30

Mitochondrial Myopathies | Common Clinical Features (3) Examples (4) Common Morphology (2)

Answer 30

Increased Creatine Kinsae Rhabdomyolysis Extraocular Muscle Defects Leber Optic Neuropathy Leigh syndrome Barth syndrome Kearns-Sayer syndrome Ragged red fibers Paracrystalline parking lot inclusions

Question 31

Spinal Muscular Atrophy | Genetics (3) Pathogenesis, Morphology, Wernig Hoffman Syndrome (5)

Answer 31

Autosomal recessive Chromosome 5 mutation SMN1 defect Loss of motor neurons in the Anterior Horn Panfascicular atrophy ``` Floppy baby* Truncal and extremity weakness Dysphagia Dsypnea Death by age 3 ```

Question 32

Malignant Hyperthermia | Mutation, Pathogenesis, Symptoms (3) Antidote

Answer 32

RYR1 mutation Anesthesia triggers increased Calcium release causing hypermetabolic state Hyperpyrexia Tachycardia Muscle spasms Dantrolene

Question 33

Tuberous Sclerosis | Genetics (3) Clinical Features (8)

Answer 33

Autosomal dominant TSC1: Hamartin defect (Chr 9q34) TSC2: Tuberin defect (Chr 16p13) ``` Hamartomas Renal Angiomyolipomas Pulomary Lymphangioleiomyomatosis Cardiac Rhabdomyomas Angiofibromas Subungual fibromas Shagreen patches Ash-leaf patches ```

Question 34

Von Hippel Lindau Disease | Genetics (3) Clinical Features (5)

Answer 34

Autosomal Dominant Chromosome 3 mutation VHL defect ``` Polycythemia CNS/Retinal Hemangioblastomas Cysts Renal cell carcinoma Pheochromocytoma ```

Question 35

Neurofibromatosis Clinical Features Type 1 (4) Type 2 (3) Mutations Type 1 and Type 2

Answer 35

``` Type 1: Chr 17 mutation (neurofibromin) Neurofibromas (plexiform can become MPNST) Optic N gliomas Lisch nodules in iris Cafe au Lait spots ``` Type 2: Chr 22 mutation (merlin) Bilateral CN VIII Acoustic Neuromas (schwannomas) Meningiomas Ependymomas