Neuro & MS Diseases: Myopathy, NMJ, MND, Neuropathy, Infections

Question 1

Inflammatory myopathies:

1. what are the 3 main classes
2. describe the general pathophysiology
3. describe the general treatment

Answer 1

1. 3 main classes: polymyositis, dermatomyositis, inclusion-body myositis
2. pathophysiology:
   - idiopathic origin
   - characterized by humoral inflammation: >50% with defined autoantibodies, some of which have strong immunogenetic association and some overlap with other AI dz
   - symmetric weakness in proximal UE&LE muscles
   - systemic organ involvement: frequently lungs-ILD, heart-arrhythmias, GI muscle weakness
   - persistent inflammation leads to endothelial cells damage/capillary loss/necrosis, as well as direct cell stress, myofiber damage
   - histology shows varying degrees of inflammation as muscle fiber degeneration/regeneration
3. Treatment includes corticosteroids and cytotoxic drugs

Question 2

Polymyositis

Answer 2

• inflammatory myopathy characterized by muscle cell degeneration and regeneration
• chronic inflammatory infiltrates (CD8+ T cells [may recognize MHC class I in muscle fibers] and MPs) in the endomysial space
• may also have arthritis, mostly in pts with Anti-Jo1 Abs
• increased serum CK
• onset usually in late teens or older (50/60yo)
• definitive diagnosis with biopsy

Question 3

Dermatomyositis

Answer 3

• inflammatory myopathy characterized by muscle cell degeneration asd well as skin involvement (skin of hands, erythematous nailbeds, eyelids, and elbows/knees)
• predominantly perivascular infiltrates, often in perimysial areas, made up of CD+4 T cells, macrophages, and dendritic cells with associated B cells, leading to perifascicular atrophy
• onset in to 2 peaks: age 5-15, and 45-65yo; commonly associated with malignancy

Question 4

Inclusion Body Myositis

Answer 4

• insidious onset (mo-yrs) of muscle weakness localized predominantly to large proximal (thigh) muscle and distal UE (finger flexors) muscles
• histo features include sarcoplasmic and nuclear inclusions and rimmed vacuoles, also marked variation in muscle fiber size
• resistant to glucocorticoid rx
• commonly seen in men over 50yo

Question 5

Amyopathic Dermatomyositis

Answer 5

• a DM type rash confirmed by skin biopsy
• no myositis but may develop myositis late
• at risk for severe ILD; can be associated with misdiagnosis

Question 6

Juvenile Dermatomyositis

Answer 6

• peak onset at age 6 & 11 yo with same features commonly seen in adult DM
• 30% to 70% have calcinosis, cutaneous ulceration, and lipodystrophy

Question 7

Antisynthetase Syndrome

Answer 7

• syndrome associated with PM or DM, seen in 20% of patients
• basis is presence of anti-Jo-1 (antihistidyl tRNA sythetase) antibody
• clinical features include myositis, non-erosive symmetric polyarthritis of small joints, and “mechanic’s hands”

Question 8

Polymyalgia Rheumatica (PMR)

Answer 8

• a syndrome characterized by AM stiffness/pain in shoulder and hip muscles
• on MRI inflammation of extraarticular synovial structures (i.e., subacromial and subdeltoid bursitis)
• often present with edema over the hands/wrists, ankles/top of feet (regional tenosynovitis and synovitis)
• occurs in pts >50yo
• elevated ESR
• highly associated with GCA (50%)

Question 9

Giant Cell/Temporal Arteritis

Answer 9

• necrotizing inflammation of the large sized arteries including the temporal artery; associated with granulomas but not glomerulonephritis; elastic membrane in arteries is disrupted
• systemic symptoms include constitutional sx, visual disturbances, temporal HAs, jaw/tongue claudication, arthralgias
• may have consistently negative throat swab, normal CXR despite URT sx; look out for thoracic aortic aneurysm
• anemia, thrombocytosis, markedly increased ESR
• tx with glucocorticoids ASAP

Question 10

X-linked Muscular Dystrophy (aka, Duchenne’s MD)

Answer 10

• deletion of the dystrophin gene results in high calcium entry and degradation of structural proteins of the sarcomere; leads to muscle atrophy and replacement by fat
• on biopsy will also see CT proliferation, and both necrotic and regenerating muscle fibers
• genetically determined, progressive, and fatal in childhood

Question 11

Becker’s Muscular Dystrophy

Answer 11

mutation of the dystrophin gene results in muscle atrophy, and replacement by fat

Question 12

Amyotrophic lateral sclerosis (ALS)

Answer 12

• degenerative disease of both upper and lower motor neurons resulting in atrophic and angular muscle fibers; will see larger but fewer APs on EMG as the intact motor neurons take over for the injured ones
• asymmetric proximal muscle weakness, fasciculations present, no sensory loss
• likely caused by gene mutation(s)

Question 13

Polyneuropathies

Answer 13

A general degeneration of peripheral nerves that spreads towards the center of the body.

• disease of peripheral nerves featuring distal>proximal weakness, sensory loss, and atrophic/angular muscle fibers
• muscle fiber denervation and re-innervation produces larger motor units (consolidated) so on EMG will see larger but fewer APs
• includes diabetic neuropathy and Guillan-Barre syndrome (ascending weakness following AI attack on myelinated peripheral nerves)

Question 14

Myopathy

Answer 14

disease of muscle fibers characterized by muscle weakness, hypotonia, and/or dystrophy; can be congenital or acquired, and there are many causes including genetic, metabolic, inflammatory, myotonic, endocrine, toxic, etc.

Question 15

Myotonic dystrophy

Answer 15

• autosomal dominant CGT repeat expansion on Chr 19, encodes protein kinase
• weakness (poor ability to contract) and myotonia (poor ability to relax) due to poor electrical activity of the muscle fiber

Question 16

McArdle’s disease

Answer 16

a metabolic myopathy caused by muscle phosphorylase enzyme deficiency, resulting in the inability to breakdown/use glycogen during exercise; glycogen accumulates in the muscle fibers

Question 17

What is the difference between myopathies in patients with hyperparathyroidism and those with hypoparathyroidism?

Answer 17

Hyperparathyroidism might present with severe weakness resembling amyotrophic lateral sclerosis.
Hypoparathyroidism patients present with muscle spasms but not weakness.

Question 18

Myasthenia gravis

Answer 18

• AI disorder in which there are abs against the nAChR at the NMJ, resulting in disuse/degradation of the nAChR and atrophy of the muscle
• characterized by fluctuating muscle weakness which worsens with activity, muscles fatigue easily (ptosis following extended upward gaze)
• on EMG, initial stimulation is normal, then decreases with increasing stimulation frequency
• can treat with AChE inhibitors, plasmapharesis, IgG infusions, immunosuppressants, steroids, thymectomy
• no ANS effects because the Abs are only against the nicotinic AChR

Question 19

Eaton Lambert syndrome

Answer 19

• AI disorder in which there are abs against the voltage-gated Ca channel on the pre-synaptic membrane at the NMJ, resulting in lack of Ca entry and no release of ACh
• characterized by proximal limb weakness (legs>arms), fatigue or fluctuating sx, reduced stretch reflexes, and transient improvement following exercise
• on EMG, initial stimulation is small, then increases with increasing stimulation frequency
• also have ANS effects (i.e., xerostomia) because the Abs prevent release of all ACh, affecting nicotinic and muscarinic receptors
• often associated with malignancy (lung tumor) so remove it to treat
• can also tx with aminopiridine (to increase ACh release), AChE inhibitors, plasmapharesis, or immunosuppressants

Question 20

Infectious/Septic Arthritis

Answer 20

1) RFs: abnormal joint architecture, age, DM, joint surgery, IVDU, endocarditis, immunosuppression
2) Pathophys: hematogenous, contiguous spread, or direct inoculation of bacteria into the joint space - hematogenous spread from occult bacteremia is most common cause; once there the bacteria adhere, promoted by ECM, and replicate
3) Microbio: S. aureus most common; then streptococcal species, and other Gram+ staph species; then Gram- bacilli: Pseudomonas in IVDU, post-surgery, DM; Gonorrhea in SAYA; Salmonella in SCD, SLE; Pasteurella in cat/dog bits; Brucella in unpasteurized milk (rare); Can also be viral - Rubella, PVB19, HCV, HBV (virus+ICs deposit in joints and cause inflammation)
4) Clinical: present with intense pain and LOF over 1-2wk period, swelling and erythema usually involving 1 joint, can be >1; most commonly knee, hip in kids; also frequently involved are shoulder, wrist, ankle; systemic symptoms can include fever (not high), malaise; if viral usually small joints of hands, short and self-resolving
5) Dx: focal joint tenderness on exam, non-specific lab findings (leukocytosis, inc. ESR/CRP), must do arthrocentesis and see >50th NTs in synovial fluid, may see lower WBCs or not

Question 21

Osteomyelitis

Answer 21

1) RFs: trauma, surgery for direct inoculation, DM or vascular insufficiency
2) Pathophys: contiguous, hematogenous, or direct inoculation of bone;
3) Microbio: S. aureus most common, also Staph epidermidis; sometimes seen are streptococci, enterococci, GN (pseudomonas in nail puncture), anaerobes, and MTB
4) Clinical: adults will have vague sx, non-specific pain around involved site, subacute/chronic, few systemic sx, may have draining sinus tract that evolved over months
5) Dx: elevated ESR/CRP, MRI shows bony destruction/sequestra; needle biopsy
6) Tx: remove surgical hardware, drain/debride, beta-lactams and vanc, linezolid (for strep, staph, and VRE), daptomycin (for G+s); typically 4-6wks of IV therapy

Question 22

Acute hematogenous osteomyelitis in children

Answer 22

1) Pathophys: capillaries make sharp loops under the growth plate, obstruction of which can lead to avascular necrosis and any minor trauma can result in hematoma, vascular obstruction, bone necrosis; these vessels lack phagocytic lining and so it’s easy for bacteria to seed the necrotic bone
2) Micro: most common are Staph aureus and Strep pneumo; in neonates it’s GBS and E. coli; in kids with SCD Salmonella also cause
3) Clinical: usually involves metaphyses of long bones (femur or tibia); with fever
4) Dx: clinical + MRI + blood cultures
5) Tx: 3 wks Abx therapy, start IV then down to PO when the patient is afebrile/can tolerate PO

Question 23

MTB infection of Bones/Joints

Answer 23

• results from hematogenous spread from pulmonary source
• MTB arthritis is a chronic granulomatous monoarthritis, usually involving the knee, hip, and ankle; synovial biopsy will show granulomas
• MTB osteomyelitis often affects the spine; pain/swelling with abscess and sinus formation, Pott’s disease with only back pain

Question 24

Vertebral osteomyelitis and spondylodiskitis

Answer 24

1) RFs: skin/soft tissue infection, GU tract infection, infective
endocarditis, IVDU, post-op
2) Pathophys: infxn of intervertebral disk and adjacent vertebrae
3) Microbio: S. aureus and Coag-negative staph most common; MTB and Brucella common where endemic
4) Clinical: localized insidious pain/tenderness in spine area in 90% of patients
5) Dx: high index of suspicion in at-risk patients
6) Tx: min 6wk IV Abx

Question 25

Pyomyositis

Answer 25

1) RFs: previous bacteremia along with (likely) some minor muscle trauma or injury
2) Pathophys: inflammation and/or infection of muscle as a result of contiguous or hematogenous spread of bacteria; get collection of pus within the muscle
3) Microbio: S. aureus accounts for 60-70%; also GAS 1-5%; C. perfringens causes gas gangrene
4) Clinical: fever, localized muscle pain, stiffness, swelling, and tenderness; pus can be aspirated
5) Dx: X-ray shows swelling/gas in soft tissue, US shows abscess, MRI is best to see focal muscle edema; aspirate to identify organism
6) Tx: drain abcess, start Abx including Vanc

Question 26

Your pt has distal weakness accompanied by areflexia and sensory loss. This finding is most consistent with the presence of myopathy or peripheral nerve disease?

Answer 26

Peripheral nerve disease.

In myopathies, the weakness is usually more proximal.