Lecture 11: Peripheral Neuropathy Part 2 Flashcards
What is Guillain Barre Syndrome?
Acute inflammatory demyelinating polyradiculoneuropathy resulting in symmetrical weakness and diminished reflexes
What breaks down myelin in GBS?
Antibodies
What are the two most common infections prior to GBS?
- Campylobacter jejuni
- CMV
What typically precipitates GBS?
Infectious illness in the weeks prior to onset.
What is the bimodal age range risk for GBS?
- 15-35
- 50-75
What is the MC variant of GBS?
Acute inflammatory demyelinating polyneuropathy
What are the initial symptoms of GBS?
- Paresthesias moving proximally
- Pain with minimal movement
- Proximal muscle weakness of the LEs that ascends symmetrically
- Muscle weakness => paralysis
- ANS dysfunction (MC: tachycardia)
- Diminished/absent DTRs
- Impaired proprioception with normal sensory
What is the purpose of serologic studies in GBS?
Ruling out other DDx. They are normal in GBS
What would LP show for GBS?
- Albuminocytologic dissociation
- Elevated CSF protein with normal WBC count
- Commonly positive within 1 week of onset
What studies confirm GBS and when are findings most prominent?
Electrodiagnostic studies after 2 weeks post onset
What findings in a MRI brain/spine with gadolinium may be seen in GBS?
- Spine: Thickening and enhancement of intrathecal spine roots
- Brain: Enhancement of cranial nerve roots
- Highly sensitive but not specific
What is the managment for GBS?
- Hospitalize until plateau is achieved (12-28d)
- Serial bedside PFTs to check pulm muscle strength
- HTN: short acting BB (esmolol) or nitroprusside
- Hypotension via IV fluids and supine positioning
- Brady: atropine or pacemaker
- Tachy: rarely severe enough to treat
- Bowel sound assessments
- I&Os for urinary retention
- Immunotherapy: Plasmapheresis vs IVIG within 4 weeks
When is plasmapheresis or IVIG indicated in GBS management?
- Non-ambulatory patients
- Ambulatory patients that are not recovering within 4 weeks
Plasmapheresis is longer
How is initial pain controlled in GBS? Severe?
- Initial: NSAIDs, gabapentin, carbamazepine, amitriptyline
- Severe: Epidural Morphine
What therapists are recommended to help with GBS?
- PT/OT
- Speech therapy
What are the poor prognostic factors for GBS?
- Old
- Rapid onset < 1 week
- Severe muscle weakness on administration
- Need for vent
- Diarrheal illness
How common is full recovery for GBS?
2/3 in 1 year
What is myasthenia gravis?
Autoimmune disorder presenting with progressively reduced muscle strength with repeated use and recovery of muscle after a period of rest.
What pathophysiology characterizes myasthenia gravis?
- Antibodies destroy ACh receptors and postsynaptic folds.
- Over-release of ACh to compensate, resulting in reduced strength and increased rest time.
What are the primary antibodies associated with myasthenia gravis?
- anti-AChR antibodies (MC)
- Anti-MuSK (Muscle-specific tyrosine kinase)
What organ disease is MC associated with myasthenia gravis?
Thymic disease
What drugs are known to induce or exacerbate MG?
- ABX (aminoglycosides, polymyxins, cipro, erythro, and ampicillin)
- BBs
- Verapamil
- Mg
- Procainamide
- Quinidine
- Chloroquine
- Penicillamine
- Statins
- Prednisone
- Timolol (topical)
- Anticholinergics
- Lithium
- Neuromuscular blocking agents
When is MG MC in males and females?
- Females: 20-30 peak
- Males: 50-70 peak
How does infantile MG occur?
Myasthenic mothers with anti-AChR antibodies that transfer via placental IgG
Transient
How does muscle weakness look like in MG?
- Fluctuating skeletal muscle weakness
- Worse in the evening/exercise
- Improves with rest
What is the common initial presenting symptom in MG?
- Ptosis
- Diplopia
- Weak EOM testing
What is bulbar weakness?
- Weakness with prolonged chewing
- Dysphagia
- Dysarthria
- Dysphonia
CN IX-XII
What happens to facial muscles in MG?
- Flat affect
- Unable to produce a smile or complete closure of eyes
What happens to the neck in MG later in the day?
Dropped head syndrome due to weakness of extensor muscles.
Where does muscle weakness tend to present first in MG?
Proximal UE
Different from GBS, which is LE.
What is a myasthenic crisis?
- Weakness of the diaphragm and intercostal muscles
- Preceded by increasing generalized muscle weakness and bulbar muscle weakness
- Occurs spontaneously or precipitated by an event.
What is the progression of muscle weakness in MG?
- Eyes/face
- Neck
- UE
- Hands
- LE
Over 3 years
What is the ice-pack test?
- Ice-pack onto closed lid for 2 minutes
- Positive response (indicative of MG) would improve the ptosis.
What serology tests are used in the workup of MG?
- AChR antibodies prior to starting immune modulating therapy
- MuSK antibodies (positive => less likely to have thymic disease)
- Seronegative MG (Most likely a purely ocular disease)
- Anti-striated muscle Ab: MC in thymoma
What is a repetitive nerve stimulation study?
- Modified motor NCS to stimulate the neuromuscular junction of a specific muscle.
- Positive: smaller EPSPs
- Negative: Normal EPSPs generate an AP.
- MC used test for MG
What is a single-fiber electromyography? (SFEMG)
- More Sensitive test
- Records APs of two muscle fibers by the same axon.
- Positive: increased interval between 1st and 2nd AP
- NON-SPECIFIC
- CI: people who have had botox in the past 12 months
MG test
What are the 4 general treatment modalities for MG?
- Sympatomatic therapy via anticholinesterase inhibitors
- Chronic immunomodulators (Glucocorticoids + immunosuppressants)
- Rapid immunomodulators (Plasmapheresis + IVIG)
- Surgical therapy (Thymectomy)
What is the first line anticholinesterase inhibitor for MG and what are the administration instructions?
Pyridostigmine bromide dose before eating or prior to muscle fatiguing activities
When do you use high dose prednisone for MG?
- Hospitalized patients undergoing rapid immunomodulating therapy
- High doses inhibit neuromuscular function
When do we use the other immunomodulators in chronic immunomodulating therapy?
- Failure to control symptoms with just prednisone
- CI to corticosteroids
When is rapid immunomodulating therapy indicated in MG?
- Myasthenic crisis
- Pre-op in MG to prevent post-op crisis
- Bridging to chronic therapy
- Maintaining remission when refractory to other treatment
When is thymectomy indicated in MG?
- Thymoma
- Young patient with generalized MG or disabling ocular MG
How do you treat mild-mod generalized MG?
- Symptomatic therapy
- Chronic immunomodulating if it remains uncontrolled
How do you treat severe generalized or rapidly progressing MG?
Rapid immunomodulating therapy + chronic + symptomatic
Add on rapid for severe
How do you manage ocular MG?
- Symptomatic + Chronic immunomodulating
- Thymectomy if needed
- Ptosis management (tape)
- Diplopia management (eye patch, opaque lens)
- Surgical intervention via opthalmology for stable ptosis or opthalmopheresis
For a patient with refractory MG, how might they be treated?
Monthly IVIG
How do we manage myasthenic crisis?
- ICU admit
- Rapid immunotherapy bridging with chronic immunotherapy
- High dose glucocorticoids if no CI.
What patient education is recommended for MG?
- Avoid food that needs a lot of chewing
- Thicken liquids
- Exercise but avoid sustained
- Written plan for patient
- Avoid the meds
- Discuss teratogenicity of pharm tx and increased risk of birth defects for MG mothers.
What is muscular dystrophy?
Inherited group of progressive myopathic disorders resulting from defects in # of genes required for normal muscle function, characterized by progressive muscle weakness and wasting
What are the two MC types of muscular dystrophy and how are they inherited?
- Duchenne type (rapid progression)
- Becker (slow progression)
Both are X-linked Recessive
How do Duchenne (DMD) and Becker (BMD) differ in terms of protein?
- DMD: markedly reduced or absent dystrophin resulting in rapid muscle damage with early use
- BMD: normal dystrophin but altered shape, resulting in later onset and milder course
What is dystrophin?
A protein responsible for muscle fiber strength
Where does DMD tend to affect first?
- Proximal muscles
- LE before UE
- Gower’s sign (hand support to get off the floor)
What does a physical exam look like for DMD?
- Unusual waddling gait
- Lumbar lordosis
- Pseudohypertrophy of calf
- Shortened achilles
- Decreased/absent DTRs
- Mild cog impairment
What are the complications of DMD?
- DCM
- Bone fx
- Progressive scoliosis
- Respiratory muscle weakness
- Wheelchair bound by 12
How does BMD tend to present?
- Milder, later onset
- Able to ambulate until age 15
- Cardiac complications are more common due to retained ability to exercise
What is the initial lab test to evaluate BMD in primary care?
Serum CK, which peaks by age 2 and is 10-20x ULN.
What is the first-line diagnostic test for BMD?
Genetic analysis, which can confirm most cases.
If we do a muscle biopsy for MD, what would we see?
- Degeneration
- Isolated “opaque” hypertrophic fibers
- Replacement of muscle by fat and CT
- Can analyze dystrophin
Muscle biopsy is rarely done now
What is the mainstay of therapy for MD?
Glucocorticoids to decrease inflammation and help repair weakened muscle cell membranes
What is the more novel treatment approach to MD?
- Exon replacement therapy via Eteplirsen (Exon 51 skipping) only for DMD with specific gene mutations
- Increased dystrophin + walking performance
What are the two Exon 53 skippers?
Golodirsen & Vitolarsen
What is the newest genetic therapy for DMD?
- Creates microdystrophin
- Only for ambulatory DMD boys aged 4-5y
- No proven clinical benefit yet
When is echo indicated in MD?
Annually
When is cardiac MRI indicated in MD?
Annually once age 7.
When are ACEIs/ARBs indicated in MD?
At 10 years old to reduce HF progression
How do we prevent the osteoporosis of MD?
- Calcium + Vit D supplementation
- IV bisphosphonates (must be able to stand upright for 30 minutes to take)
- PT and exercise
What is the MCC of death in someone with BMD?
HF due to DCM
What is Charcot-Marie-Tooth?
Spectrum of disorders due to mutation in myelin gene
What is the MC type of hereditary neuropathy?
Charcot-Marie-Tooth (CMT)
How is CMT inherited?
Autosomal dominant
MC in males
How does CMT typically present?
- Slow, progressive, distal leg weakness within 1st 3 decades
- Foot drop
- Pes cavus (high arch, hammer toes)
- Foot deformities
What happens to the legs in CMT?
Atrophy of the muscles, resulting in inverted champagne bottle legs or stork leg deformities
What happens to the UE in CMT?
- Hand weakness
- Clumsiness in using small objects
- Claw hand
What happens to the senses and reflexes in CMT?
- Diminished/absent DTRs
- Diminished proprioception and vibratory sense
- Pts don’t complain about subjective sensory symptoms
- Sensory gait ataxia
- Positive romberg
How do we workup CMT?
- EMG/NCS to confirm neuropathy.
- Genetic testing after EMG to confirm dx of CMT
How do we treat CMT?
- Supportive
- PT
- Ankle-foot orthotics
- Foot surgery
- Avoid: Metro, macrobid, FQs, amiodarine, and colchicine (Neurotoxic drugs)
What is the prognosis of CMT?
Full life span with diminished quality.
What is the MC DM complication?
Diabetic neuropathy
What exactly happens that causes DM neuropathy?
Vasa nervorum abnormalities occur
How does distal symmetric polyneuropathy present?
- MC form of DM neuropathy
- Axonal neuropathy
- Stocking-glove pattern
- Dulled perception
- Absent ankle DTRs
- Calluses and ulcerations in high pressure areas
How do we treat distal symmetric polyneuropathy?
- Amitriptyline
- Duloxetine
- Pregabalin
- Gabapentin
- DM control
What is the least common DM neuropathy?
Isolated peripheral neuropathy
Mainly seen in old pts
What are the most common nerves affected in isolated peripheral neuropathy?
- Ocular: CN III, IV, VI, or femoral nerves
- Diabetic amyotrophy (lumbosacral radiculoplexus neuropathy) in anterior thigh with quads wasting
How do you manage isolated peripheral neuropathy?
Same as distal + lidocaine patches
What kind of DM typically causes autonomic neuropathy?
Long-term DM
What is the primary symptom of autonomic neuropathy?
GI dysfunction => gastroparesis
How do you manage GI dysfunction due to autonomic neuropathy?
- Small, frequent meals
- Metoclopramide (careful of tardive dyskinesia and extra pyramidal symptoms)
- Loperamide for diarrhea
- Fiber for constipation
What medication may help with bladder dysfunction/urinary retention in autonomic neuropathy?
Bethanechol (cholinergic agonist) that increases detrusor muscle tone
What medications may help with orthostasis in autonomic neuropathy?
- Fludrocortisone
- Midodrine (alpha agonist)
How do you treat ED due to autonomic neuropathy?
PDE-5 inhibitors
What body parts is alcoholic neuropathy MC in?
Legs
What exactly is neurotoxic about alcohol?
Acetaldehyde, which is a metabolite of ethanol.
Impairs axonal transport
What is the MC presenting complaint of alcoholic neuropathy?
Paresthesias of the feet and toes
How do you manage alcoholic neuropathy?
- Stop drinking
- Thiamine supplementation
- Low doses of TCAs or gabapentin
What is beriberi more formally known as?
Thiamine/B1 deficiency
What is thiamine’s use?
- Coenzyme in carb metabolism
- Water-soluble
What is the primary risk factor for dry beriberi?
Chronic alcohol abuse
Who does dry beriberi occur in?
Inactive patients with low caloric intakes
How does dry beriberi present?
Symmetric peripheral sensorimotor neuropathy with loss of reflexes
What are the more complicated CNS involvements of beriberi?
- Wernicke-Korsakoff syndrome
- Wernicke encephalopathy
- Korsakoff syndrome
What is the most reliable test for checking thiamine?
- Thiamine loading test to assess erythrocyte transketolase activity (EKTA)
- Positive: 10-25% increase in EKTA after thiamine administration
How do you treat thiamine deficiency?
Thiamine until proper nutrition is restored
What exactly occurs due to a lack of Vit B12?
Damage to the myelin sheath
What is the MCC of Vit B12 deficiency?
Pernicious anemia
How does a B12 deficiency present?
- Paresthesias of the hand, followed by LE
- Sensory changes
- Sensory ataxia
- Anemia
- Glossitis
- Optic atrophy
- Behavioral changes in severe cases
How do we confirm B12 deficiency?
Reduced serum B12/cobalamin levels
What serologic tests may be ordered to check for pernicious anemia?
- Antiparietal cell antibodies (90%)
- Intrinsic factor antibodies (60%)
What is the standard treatment for B12 deficiency?
- 1000 mcg of IM B12 weekly for 1 month
- 1000mcg a month
How does neuropathy associated with gastric surgery present?
- Rapid, significant wt loss
- Recurrent, protracted vomiting
- Numbness and paresthesias in the feet is the initial symptom
Why are the feet most commonly affected in neuropathies?
The longest nerve/axon is the sciatic nerve
How do you treat gastric surgery neuropathy?
Vitamin supplements, especially thiamine
