Peripheral Nerve Disorders II - Exam 4 Flashcards
What is the etiology of muscular dystrophy? How does a pt get muscular dystrophy?
Complex set of INHERITED myopathic disorders.
inherited: X linked recessive!!
Muscular dystrophy presents as ________ WITHOUT _______ often ______. What lab value will be elevated?
muscle weakness and wasting
WITHOUT sensory loss
progressive
elevated CK
What are the 2 types of MD that we learned about in lecture? Which one is worse? What percentage of all MD?
Duchenne MD** worse: 23%
Becker MD: 10%
What groups of muscles are commonly affected in both Duchenne and Becker MD?
shoulders, forearms and thighs
How does Duchenne MD compare to Becker MD? include protein _____
Duchenne is more severe s/s
-dystrophin (protein) is markedly reduced or absent
Becker: similar to DMD but later onset and milder course
-dystrophin levels are normal, but protein is qualitatively altered (misshapen)
In MD the genetic defect is located on the _______. What is it? What does it code for?
short arm of X chromosome
dystrophin: (protein): helps anchor the outside of the muscle cell to the inside of the muscle cell. plays a huge role in strength of muscle
Can DMD be recognized in early pregnancy?
YES! can be recognized in early pregnancy in about 95% of women
What is the trend with regards to MD as a pts ages?
older the pt gets the higher likely they are to die, survival rates into adulthood is not great
58% of males 20-24
How does Duchenne MD typically present?
weakness usually around 2-3 years old
starts proximal and moves distal, weakness is progressive
Gower’s sign
What is Gower’s sign? What disease is it commonly seen with?
using hands to push up to stand, shows progressive muscle weakness
MD
Besides weakness, name additional s/s of Duchenne MD.
What are the 4 typical comorbidities associated with Duchenne MD?
primary dilated cardiomyopathy: MITRAL regurg. can lead to heart failure and arrhythmias in later stages
fractures
progressive scoliosis
impaired pulmonary function due to respiratory muscle weakness
______ is the clinical distinction between Becker and Duchanne MD. How long can they remain _______? ______ is usually worse when compared to Duchanne
retained strength
Usually ambulatory at least until age 15 and commonly into adult life
WORSE: cardiac dz in Becker due to retained ability to exercise
As a PCP, what 3 tests should you order if you suspect MD? Then what should you do?
serum CK
EKG
EMG
refer to neuromuscular specialist/ MD center
What will the serum CK show in a pt with MD? When is it at its peak? Is CK elevated or decreased in carriers?
elevated in DBMD patients prior to clinical signs of disease
Peaks ~age 2; usually 5-10x ULN or more; then falls by 25% per yr
CK increased up to 10x ULN in carriers - 50% DMD carriers, 30% BMD carriers
What will the EKG show in a pt with MD? What will the EMG show?
tall right precordial R waves, increased R/S ratio, deep Q waves in I, aVL, V5-6
DMD also associated with conduction disturbances leading to variety of arrhythmias
EMG: myopathic changes
_____ is the first line and confirms dx test in MD
Genetic analysis
What will a muscle bx show in a pt with MD? What about dystrophin specifically? Give DMD and BMD results
degeneration, regeneration, isolated “opaque” hypertrophic fibers, replacement of muscle by fat and connective tissue
DMD - most pts have total or near-total absence of dystrophin
BMD - ~85% with abnormal size and amount; ~15% with normal size, abnormal amount
______ is the mainstay of tx for MD. When is it recommended to start? What age? What are the dosing considerations?
Glucocorticoids (prednisone)
start before significant physical decline occurs
boys 4+ years old whose motor skills have plateaued or starting to decline
do NOT abruptly stop, need to taper and may need stress dosing
What are 3 good parameters to assess benefits of glucocorticoids in MD?
Timed muscle function tests
pulmonary function tests
age at loss of independent ambulation
________ : systemic glucocorticoid specifically for DMD. What is potential SE? More or less SE when compared to prednisone?
Deflazacort (Emflaza)
may stunt growth
LESS general SE when compared to prednisone
________ is the newest glucocorticoid option for MD but it is expensive
Vamorolone (Agamree)
________ binds to exon 51 of mRNA, causes skipping of exon 51 in translation of the DMD gene. What percent of DMD pts have this variant? What is the theoretical end result?
Eteplirsen (Exondys 51)
13% of DMD pts have exon-51 variants
increases dystrophin
______ and ________ Causes skipping of exon 53 in translation of the DMD gene. What percent of DMD pts have this variant?
Golodirsen (Vyondys 53) and Vitolarsen (Viltespo)
8% of DMD pts have exon-53 variants
________ Causes skipping of exon 45 in translation of the DMD gene. What percent of DMD pts have this variant?
Casimersen (Amondys 45)
8% of DMD pts have exon-45 variants
________ Adeno-associated virus capsid (AAVrh74) with a gene that encodes for ________. What is it designed to do?
Delandistrogene moxeparvovec (Elevidys)
microdystrophin
Designed to deliver to skeletal and cardiac muscle
How are the gene editing drugs given to pt? How is Delandistrogene moxeparvovec (Elevidys) given to pts?
gene editing: weekly infusions
Delandistrogene moxeparvovec (Elevidys): ONE IV infusion. that is it
_______ Promotes read-through of inappropriate nonsense (stop) codons, allowing bypass of nonsense codon and continuation of translation process to produce dystrophin
ataluren (PTC 124)
NOT YET APPROVED IN THE US
What are 2 additional emerging tx options for MD?
Myostatin inactivating antibodies: Myostatin is a protein that inhibits muscle growth
Cell Therapy
_______ Promotes muscle formation and reduces fibrosis, fatty replacement, and inflammation of muscles and IS NOT restricted to specific gene variants. What drug class?
Givinostat (Duvyzat)
histone deacetylase inhibitor
When is Givinostat (Duvyzat) commonly used? What do you need to monitor? When can you NOT give it?
adjuvant medication in MD on top of gene editing drugs and prednisone
monitor platelet count, triglycerides, and QTc interval
Do not give if baseline platelets <150,000
What the additional medications needed to tx cardiac comorbities? What testing?
steroids may reduce new-onset and progressive cardiomyopathy,
ACEi and/or ARB beginning at age 10
Echocardiogram yearly at onset
Cardiac MRI beginning around age 7 and then annually
What do you need to counsel pts on with regards managing/preventing orthopedic complications in MD?
Gentle aerobic exercise - swimming, cycling, assisted exercise
Physical therapy to help reduce contractures
nutrition: need calcium and Vit D
orthotics, braces, surgical release of contractures, tx fractures, standing wheelchairs
The DMD prognosis may see early improvement when the kid is ______. The median survival rate in DMD is ______.
The mean survival rate in BMD is ______.
3-6 years old but will have gradual deterioration
DMD: 35 years old
BMD: mid 40s
What is the MC cause of death in BMD?
heart failure from dilated cardiomyopathy
can consider heart transplant
Charcot- Marie- Tooth is a spectrum of disorders caused by a specific mutation in one of several ______. What does it result in?
myelin genes
defects in myelin structure, maintenance, and formation
**______ is the MC type of hereditary neuropathy. How is it inherited? MC in males or females?
Charcot-Marie-Tooth (CMT)
autosomal dominant
3x more common in males
When does CMT usually present? What is the presenting symptom? How does it progress?
1st-3rd decade of life
distal leg weakness (e.g., foot drop): usually foot deformities or gait disturbances in the childhood or early adult life
slow progression moves distal to proximal, eventually involves UE and LE
What will the MSK exam of the lower extremities reveal in pt with CMT?
Foot Drop - reduced or absent dorsiflexion
Pes cavus - high arch and hammertoes
Atrophy of muscles below knee - “inverted champagne bottle” legs or “stork legs”
What will the MSK exam of the upper extremities reveal in CMT?
Claw hand - due to atrophy of muscles in hand
Hand weakness - poor finger control, poor handwriting, difficulty with zippers and buttons, and clumsiness with manipulating small objects
What will the neuro exam reveal in a pt with CMT?
What 2 types of sensation will be diminished in CMT?
diminished proprioception and vibration (due to LARGE fiber neuropathy)
pt will not complain of sensory loss because they never had the sensation to begin with
What will the EMG and NCS of a pt with CMT show? Why is it important to correctly dx CMT early?
Confirms evidence of neuropathy
If negative, consider a different diagnosis
need to start interventions ASAP especially PT
______ confirms diagnosis of CMT. Why?
genetic testing
also helps to rule out other genetic sources of neuropathy
What is the tx for CMT?
SUPPORTIVE CARE!!! no specific dz modifying therapy
PT: daily stretching
ankle foot orthotics/foot sx if needed
**What 2 medications need to be avoided in CMT? What type of medications are they?
vincristine and paclitaxel
both chemo drugs
What is the prognosis of a pt with CMT?
slow progressing dz and pts often live a full life span but have an impaired quality of life
What do you need to monitor for in CMT?
Screen periodically for conditions that can exacerbate neuropathy:
Diabetes mellitus
Vitamin deficiencies
Immune-mediated neuropathies
What is Guillain-Barré Syndrome (GBS)? **What 3 things does it result in?
acute, IMMUNE-MEDIATED (not genetic) polyradiculoneuropathy that results in
weakness, paralysis, and diminished reflexes
What is the usual trigger for GBS? **specifically _______. What does it lead to?
Inflammatory/immune-associated trigger (usually a recent infection)
-> specifically Campylobacter jejuni
leads to production of ANTIBODIES that cause myelin destruction or axon damage in peripheral nerves
risk of GBS increases as you _____, MC in males or females?
more common as a pt ages
slightly more common in males
What is the MC form of GBS?
Acute inflammatory demyelinating polyneuropathy (AIDP)
How does GBS present? When do s/s usually progress? What will pts commonly complain of? When is the nadir (lowpoint) of the dz?
new acute neuro symptoms that present as SYMMETRICAL muscle weakness that usually begins the legs and ascends
“rubbery legs” and weakness tends to progress
Symptoms usually progress over a period of 2 weeks
nadir: by 4 weeks
____ of GBS occurs a few weeks after acute infectious process usually ____ or _____ in nature
66%
GI or respiratory in nature
with campylobacter jejuni the MC etiology
rare, but possible to see GBS after ??????
surgery, trauma, bone marrow transplantation, or systemic diseases like SLE and Hodgkin lymphoma
In GBS _____ symptoms often precede ____ symptoms. _____ is often present in shoulders, back, thighs and buttocks
Sensory symptoms often precede motor symptoms
deep, aching muscular pain
10% of GBS patients will present with ______ initially. 10-30% of GBS pts will develop ______ requiring _______
arm or facial muscle weakness
respiratory weakness
ventilation
What are 3 other neuro symptoms commonly seen in GBS?
reduced or absent DTR in 90% of pts
CN or bulbar palsies: Bells Palsy, oropharyngeal weakness, oculomotor weakness
dysautonomia: think reduced gut motility (ileus) urinary retention, HTN or hypotension, Tachy or bradycardia, fever
What will the brain/spine MRI with gadolinium contrast show in a pt with GBS?
May show thickening and enhancement of cranial and spinal nerve roots and cauda equina
sensitive but not specific for GBS
What will NCS/EMG show in a pt with GBS? What is important to note?
Confirms polyneuropathy; differentiates between axonal and demyelinating subtypes
Normal study early on does not rule-out GBS aka can also be normal and still have GBS
**What does LP with CSF analysis show in a pt with GBS? **What is important to note? Who should it be done on?
**elevated CSF protein with a normal CSF WBC
**CSF can also be NORMAL
ALL pts that are suspected to have GBS
What is the management for GBS? _____ needs to be completed beside every 4 hours. ______ to avoid contractures
-hospitalization!! due to risk of respiratory failure
- PM: NSAIDs, gabapentin or carbamazepine or amitryptyline. careful with opioids due to risk of ileus
-LMWH for DVT prophylaxis
-tx HTN (esmolol or nitroprusside) or hypotension (IV fluids or pressors PRN)
- Tx tachy/bradycardia
Serial bedside PFTs - every 4 hours assessing pulmonary muscle strength
daily ROM exercises to avoid contractures
What is the GBS SPECIFIC tx options? Which one is preferred? When does it need to be administered?
Plasmapheresis or IVIG** preferred
within 4 weeks of symptom onset
_____ removes autoantibodies, immune complexes, cytotoxic constituents. What is the tx schedule?
Plasmapheresis
4-6 treatments over 8-10 days
______ derived from donated plasma; supplements the pts immune response. What is the tx schedule?
IVIG
requires less time - one tx daily x 5 d
What is the timeline associated with GBS? What is the average time to recovery? _____ is a very common reported continued symptom
s/s progression for up to 2 weeks
nadir around 4 weeks
plateau of unchanging symptoms for 2-4 weeks
then gradual improvement of symptoms
200 days
fatigue
What are poor prognostic factors for GBS?
older than 60
rapid onset of weakness
severe weakness at time of admission
respiratory weakness/vent support
severe NCS/EMG abnormalities
preceding diarrheal illness
Motor neuron action potential releases _____ into the synaptic cleft. What is presynaptic rundown?
acetylcholine (ACh)
temporary depletion of presynaptic ACh
_____attaches to the ACh receptor (AChR) on the ______ of the muscle cell
ACh-AChR binding results in ______
Acetylcholine
postsynaptic fold
muscle contraction
______ breaks down Ach and prevents excessively prolonged _______
Acetylcholinesterase
muscle contraction
What is the etiology of myasthenia gravis?
neuromuscular disease - weakness and fatigability of skeletal muscles as a result of autoimmune attack that causes a decrease in acetylcholine receptors (AChRs) at NMJs and loss of postsynaptic folds
In myasthenia gravis, what happens as a result of the decrease in acetylcholine receptors (AChRs) at NMJs and loss of postsynaptic folds?
Over-release of ACh from axon terminals to try to create an adequate response which results in presynaptic rundown and loss of acetylcholine receptors (AChRs) which results in progressively reduced muscle strength with repeated use
What are the 2 types of autoantibodies that are associated with myasthenia gravis? Which one is more common?
anti-AChR - 80-90% of MG patients
anti-MuSK - muscle-specific tyrosine kinase
Which MG autoantibody are associated with an underlying thymus disorder?
anti-AChR
also possible to have the ______ form of MG. What will the test show?
Seronegative MG
neither antibody but still have clinical dx
What is the bimodal peak of MG? What is the cause if it is seen in infants? MC in males or females?
females age 20s-30s, males age 50s-60s
Infantile - transient neonatal MG occurring in infants of myasthenic mother
slightly MC in women
What are the risk factors for MG?
infections
hormonal changes
thymic abnormalities
medications: abx, BB, statins, anticholinergics, botox
**What are the 2 cardinal features of MG?
weakness and fatigability
weakness increases as the day progresses (using the muscles) and IMPROVE with sleep
aka muscles get tired of doing normal activities that would not be an issue for a normal person (chewing, speaking, swallowing, holding the neck up, holding eyelids open)
______ is the initial symptom in over 50% of patients. ____ is NOT affected
ocular (ptosis, diplopia, weak EOM)
pupils are NOT affected
_____ and ____ are often asymmetric in myasthenia gravis. What 4 things are usually normal?
ocular palsies and ptosis
Normal pupillary responses, sensation, coordination, DTRs
What is a myasthenic crisis? What usually precedes the crisis? Can it be triggered?
life-threatening exacerbation involving respiratory system. Weakness of diaphragm and intercostal muscles → hypoventilation, respiratory failure. NEED TO BE IN ICU!!
increased generalized weakness: pt needs to seek care immediately!!
yes! sx, childbirth, infection, tapering of immunosuppressive medications or can be spontaneous
What is the ice pack test? What is the expected result if the pt has myasthenia gravis?
Ice Pack Test - for patients with ptosis
Ice pack on closed eyelid for 2 minutes.
Cold improves neuromuscular transmission
Positive (suggestive of MG) if ptosis improves
_______ is positive in 85% of all MG pts, 50% of ocular MG. Does a negative test exclude MG?
Anti-AChR antibodies
negative does NOT exclude
______ will be positive in 35-50% of MG pts who are anti-AChR negative
Anti-MuSK antibodies
_________ will be positive in 30% of MG pts, 80% of thymoma pts
Anti-striated muscle (anti-SM) antibody
_______ is the MC electrodiagnostic test for MG. What is another name for it? What will it show if the pt has MG? Normal?
Repetitive Nerve Stimulation
modified NCS
action potentials in MG pts drop rapidly by 10-15% for each show
action potentials stay normal in healthy pts
________ also known as ______ is used only if other tests are inconclusive. Most sensitive test; (+) if increased interval between action potentials
Single-fiber electromyography
modified EMG
What imaging would you want to order when working a pt up for myasthenia gravis?
chest CT to look at thymus
enlargement of the thymus is a pt over 40 is highly suspicious for MG
What are the 4 major tx options for MG?
What is the tx for mild/moderate MG?
Start with symptomatic tx
Add chronic immunomodulating tx if still uncontrolled
What is the tx for severe generalized MG or rapidly progressive MG?
Start with rapid immunomodulating therapy
PLUS chronic immunomodulating therapy
PLUS symptomatic therapy
What is the tx for refractory MG disease?
Pts who fail to respond to symptomatic and chronic immunomodulating therapy - monthly IVIG
What is the tx for myasthenic crisis?
ICU admission with ventilation assistance
Rapid immunotherapy bridging with chronic immunotherapy
high dose glucocorticoids preferred if no CI due to short onset of clinical effect
_______ is the Anticholinesterase Inhibitor that is first line in MG
pyridostigmine (Mestinon)
______ MOA Stops degradation of ACh by enzymes in the neuromuscular junction.
More improvement with non-ocular weakness
pyridostigmine (Mestinon)
What are the pt education dosing instructions for pyridostigmine (Mestinon)?
tid-qid: Typically just before eating or other activities that cause muscle fatigue
______ is the first line therapy for chronic immunomodulating therapy in MG. When are high doses used?
Glucocorticoids - Prednisone
only used in hospitalized patients undergoing rapid immunomodulating therapy
What are the immunomodulators used in chronic immunomodulating MG therapy? When are they used?
2nd line: Azathioprine, mycophenolate mofetil (CellCept), and cyclosporine
CIs to corticosteroids, or if symptoms are not controlled with adequate doses of prednisone
What are the rapid immunomodulating therapies options in MG? When are they indicated?
plasmapheresis and IVIG
-Myasthenic crisis
-Pre-op treatment in MG - helps to prevent post-op “crisis”
-Bridging to slower acting immunotherapy
-Assist in maintaining remission in MG patients who are not controlled on other tx
_____ may result in improvement or remission of MG and should be offered to any pt with ______
Thymectomy
thymoma on imaging
What is the criteria to offer thymectomy to a MG pt who does NOT have thymoma present on imaging?
-Young (<50 y/o)
-Have generalized MG or disabling ocular MG
-Best results if AChR positive but can still offer to AChR-negative pts
What is the tx for just ocular MG?
Symptomatic and chronic immunologic pharmacotherapy
Thymectomy if indicated
tx ptosis and diplopia: crutches, eyelid adhesive strips, artificial tears, eye patch, eyeglass lens occlusion, sx intervention if needed
What is the clinical course associated with MG? progression usually peaks in first ____ of illness. What is the order of affected parts of the body?
slow progressive course of relapses and remissions
3 years
eyes/face → neck → UE → hands → LE
What are some MG pt education points? What is the prognosis?
less than 5% mortality rate and most patients live a normal life-span
chronic alcohol abuse puts a pt at high risk for ____ deficiency. _______ is when the CNS involvement occurs
Thiamine (B1) Deficiency
Wernicke-Korsakoff Syndrome
What are the best sources of Thiamine (B1)?
fortified grains, pork, seeds, nuts
What is dry beriberi? What is the predominant symptom?
ymmetric peripheral sensorimotor neuropathy with loss of DTRs
Mild sensory loss and/or burning dysesthesias in the toes and feet
Aching and cramping in the LE - PAIN may be the predominant symptom
______ nystagmus→ ophthalmoplegia, ataxia, confusion. What deficiency?
Wernicke encephalopathy
thiamine (b1)
_______ amnesia, confabulation, impaired learning ability. What deficiency?
Korsakoff psychosis
thiamine (B1)
______ is the test to dx thiamine deficiency. Need to order _______ before and after thiamine dose. What is considered a postive result?
Thiamine or Thiamine pyrophosphate (TPP)
Erythrocyte transketolase activity (ETKA) test
positive result is a 10-25% increase in ETKA; test is lengthy and not readily available
What does inadequate absorption or poor intake of B12 (cobalamin) lead to? **What is the MC cause? What are 3 additional causes mentioned in lecture?
demyelination
pernicious anemia
vegan diets, GERD meds (H2 blockers, PPIs) and metformin
What are s/s of B12 deficiency? What is the contradicting symptom mentioned in lecture?
paresthesias in hands, sensory changes, anemia, red swollen tongue, angular cheilitis, behavioral changes
hyperreflexia but ABSENT ACHILLES REFLEX
What labs do you order to check B12 levels? order _____ or ______ if result is borderline. What will the results show?
Serum cobalamin (B12 levels)
MMA and homocysteine: will be elevated in the absence of B12
In B12 deficiency, after treated with ______ at least 50% of patients exhibit _________
IM cyanocobalamin must be IM/IV
one or more permanent neurologic deficits
_________ associated with rapid, significant weight loss and recurrent, protracted vomiting. How does it present? What is the tx?
Polyneuropathy may occur after gastric surgery for ulcer, cancer, wt loss
numbness and paresthesias in the feet
parenteral vitamins because cannot do anything that involves the GI tract because problem is GI related
_______ is the MC DM complication. Morphologic abnormalities of the ______ present early in the disease course
diabetic neuropathy
vasa nervorum
_______ is the MC form of diabetic peripheral neuropathy. Pts lose sensation in a ________. _____ symptoms appear first
Distal symmetric polyneuropathy
stocking-glove pattern
sensory: dulled perception of vibration, pain, temperature, light touch
in distal symmetric polyneuropathy, _______ occur early in course and ______ occur in high pressure areas
Diminished ankle DTR
Calluses and ulcerations
_______ is the MC diabetic mononeuropathy
median mononeuropathy at the wrist
______ is the MC diabetic polyradiculopathy. How does it present?
Diabetic amyotrophy
Severe pain in anterior thigh followed in a few days-weeks by weakness and quadriceps wasting with improvement in pain
What is the tx for painful DM neuropathies?
strict glycemic control
antidepressants: duloxetine (Cymbalta) or venlafaxine (Effexor)
TCAs: amitriptyline (Elavil)
anticonvulsants: gabapentin (Neurontin) or pregabalin (Lyrica)
adjunct: +/- topical therapies: capsaicin and lidocaine gel
What are 6 types of autonomic diabetic neuropathies? What is the generic tx of each?
Gastroparesis: d/c GLP-1, then try metoclopramide, small frequent meals
diarrhea: hydration and supportive care
constipation: increased fiber and fluids
bladder dysfunction
orthostasis
erectile dysfunction
What are the serious SE of metoclopramide?
Tardive dyskinesia and extrapyramidal SE - especially > 3 mo use, FDA cautioned against using for long term use
alcoholic neuropathy is a gradually progressive ______ caused by neurotoxicity of _______. Can affect ______, _____ and _______
axonal polyneuropathy
acetaldehyde (metabolite of ethanol)
sensory, motor and autonomic functions
What is alcoholic neuropathy complicated by?
demyelination when co-existing nutritional deficiency present (especially B vitamin deficiencies)
alcoholic neuropathy is commonly seen more in the ______. These patients are more susceptible to ______. ______ is seen later in disease process when disease is more severe
legs: paresthesias of feet/toes
compression of peripheral nerves
autonomic disease
_______ is alcoholic neuropathy that also presents with CNS symptoms
Wernicke-Korsakoff
What is the tx for alcoholic neuropathy? What is the prognosis?
Thiamine supplementation
Improved nutrition and cessation of drinking!!
Low doses of TCAs, gabapentin, or mexiletine (antiarrhythmic rx) may help with burning dysesthesia
varies with compliance with treatment but
complete recovery from severe neuropathy is uncommon
