Neuromuscular diseases Flashcards
What symptoms do UMN diseases produce?
- Spastic tone,
- hyperactive tendon reflexes,
- pathological reflexes (babinski)
- Emotional lability (inappropriate laughing and crying)
What symptoms do the damage of sensory and autonomic nerves produce?
- Numbness,
- abnormal painful sensations
- Bowel and bladder disturbance
- Alterations in sensation, sweating, heart rate and blood pressure
- (think of all the ANS tissue targets and what might happen if they were not innervated with proper tone)
What symptoms do LMN diseases produce?
• Muscle atrophy, fasciculations, diminished tone and reduced or absent reflexes
If there are no sensory problems associated with weakness found by exam, what does that suggest?
- NMJ problem
- Motor neuron problem
- Muscle disease
- (if there are sensory problems as well that suggests an entire nerve problem)
What goes on your differential if there is a rapid progression of symptoms? (hours to days)
- NMJ disorders like MG, botulism and organophosphate poisoning
- Acute demyelination in Guillan Barre syndrome
- Electrolyte disturbance
- Toxic myopathies
What are the three distribution patterns of weakness?
- Proximal, distal and cranial
- Proximal is weakness in posture and walking (climbing stairs, getting out of a chair)
- Distal weakness, indicative of neuropathy, is in the hands and feet (foot drop, trouble holding things or turnig a key)
- Cranial is seen in MG, droopy eyelids (ptosis), double vision and speaking/swallowing abnormalities
The symptom “stiffness” can reflect what problem?
- Myotonia, delayed relaxation of muscle following voluntary contraction
- A problem either with excitation machinery being overactive OR the membrane can’t regain the hyperpolarized potential
What enzyme studies can you request for NMJ disorders?
- Muscle necrosis results in elevated levels of serum creatinine kinase (CK)
- Highest levels of CK occur with myoglobinuria
- Muscular dystrophies and inflammatory myopathies have moderate elevations
What are some signs to look for in infants with NMJ disorders?
- Decreased tone (floppy baby)
* Delay in motor milestones
What are some electrodiagnostic studies you can request if you are suspecting a neuromuscular disease?
• Want to distinguish neuropathic from myopathic
• NCS - nerve conduction studies
○ Give you a baseline and numbers to follow for the course of the disease
○ Broadly differentiate between primary demyelinating (super slow conduction) and axonal neuropathies
• Needle EMG
○ Often complement to NCS and helps differentiate myopathic from neuropathic
○ If a nerve problem, the whole motor unit fails
○ If muscle problem, individual fibers of the motor unit fail
• Repetitive nerve stimulation
○ Allows you to look at a muscle in the context of extreme work, and in MG you see depletion take its toll
What should go on your differential of “myopathies”?
• Muscular dystrophies
○ Duchenn/becker, limb girdle, FSH
• Myotonic disorders
○ Myotonia congenital, myotonic dystrophy
• Inflammatory myopathies
○ Polymyositis, dermatomyositis, inclusion body myositis
• Endocrine myopathies
• Metabolic myopathies
○ Glycogen storage, lipid myopathy, mitochondrial myopathy
• Toxic myopathies
• Periodic paralysis
What does ALS stand for?
- Amyotrophic lateral sclerosis
- Characterized by progressive weakness and wasting from degeneration of brainstem and spinal cord lower motor neurons
- Coexisting spasticity and hyperreflexia b/c of UMN syndrome
- Most cases are sporatdic, though less than 10% are familial
- Initial clinical symptoms may be limited to asymmetric limb weakness in the presence of fasciculations
- Foot drop or marked hand deformity resulting from interosseus wasting may be seen
- Pathological reflexes can be seen
- Sensory exam is normal, but speech may develop a slurred or spastic quality
What initial signs and symptoms point to ALS?
- Initial clinical symptoms may be limited to asymmetric limb weakness in the presence of fasciculations
- Foot drop or marked hand deformity resulting from interosseus wasting may be seen
- Pathological reflexes can be seen
- Sensory exam is normal, but speech may develop a slurred or spastic quality
What is the average survival of ALS after ddx?
- 3-4 years, but 10% survive 10 years or longer
- Fatal aspiration pneumonia is common from defects in swallowing
- Also diaphragm weakness is a problem
What is the average survival of ALS after ddx?
- 3-4 years, but 10% survive 10 years or longer
- Fatal aspiration pneumonia is common from defects in swallowing
- Also diaphragm weakness is a problem
What are the treatments for ALS?
- Primarily symptomatic
- Medications for cramps, spasticity, excess saliva and inappropriate laughing or crying
- Riluzole has been shown to slow progression slightly (extend life 3 mo)
- Braces and durable medical equipment for mobility
- Alternative communication devices
- Feeding tube and ventilation
Many different inherited neuropathies are often lumped into what disease name?
- CMT - Charcot Marie Tooth
- Autosomal dominant forms are CMT1 and CMT2
- CMT1 is slow nerve conduction and hypertrophic demyelinating neuropathy
- CMT2 is normal nerve conduction velocities and axonal degeneration
- There are many new genes being liked to the disease, and the only one we talked about in detail is CMT1A
What do most patients with CMT present with?
• One of three phenotypes based on the age at symptom onset
• Most common - distal hand and foot weakness and sensory loss develops slowly in the first two decades of life
○ Patients don’t need much more than walking aides
• Second phenotype - already impaired as infants and experience delayed walking
○ Many are later confined to wheelchair
• Third phenotype - adult onset that appears at 40ish years
If the same gene that CMT1A has duplicated is instead deleted, what’s the result?
- Gene is PMP22
* If this gene is deleted, it results in HNPP, hereditary neuropathy with liability to pressure palsies
What’s up with CMT1A?
- Duplication of the DNA containing the peripheral myeling protein gene PMP22
- If this gene is deleted, it results in HNPP, hereditary neuropathy with liability to pressure palsies
What electricity test is used most in diferentiating CMT disease?
- NCVs - nerve conduction velocities
- Cutoff for demyelinating and axonal forms are 38m/sec
- There are some intermediate forms though 35-45m/sec
- This test and family history guides you in asking for certain genetic tests
What is the treatment regime for CMT?
- PT to maintain muscle strength and ROM
- OT to improve hand function and provide tools to aid activities of daily living
- Orthotics for ambulation aid and reduce falls
- Treat neuropathic pain
What is the most common type of diabetic neuropathy?
- Distal sensory or sensorimotor polyneuropathy
- Initially complain of numbness and burning dysesthesias in their feet
- Spreads to legs and eventually hands
- Weakness of foot dorsiflexor muscles results in a slapping foot drop gait
- Grip strength and fine hand dexterity may be diminished as well
What ANS problems can happen in diabetic neuropathy
- These can occur with or without other evidence of neuropathy
- Postural hypotension
- Diarrhea
- Impotence
- Urinary retention
- Increased sweating
On examination what does one see in diabetic neuropathy?
- Pin sensasion loss in a stocking glove distribution but the distribution is often somewhat asymmetric
- Loss of position, vibration, light touch
- Decreased reflexes in a large fiber pattern
- Great loss of pain and temperature sensation - indicates predominantly small fiber injury
- Pain may have a dull aching quality in the limbs and also a distal, burning discomfort most prominent at night
What’s up with lumbosacral plexopathy?
• A complication in diabetic neuropathy
• Characterized by acute onset of asymmetrical proximal weakness and pain of the legs
• Frequently occurs at the onset of diabetes and may be associated with weight loss
• Mononeuropathies can affect almost any peripheral nerve as wella s cranial nerves, particularly the extraocular muscles
○ 3rd and 6th nerve palsies
What’s up with 3rd and 6th nerve palsies?
• Mononeuropathies can affect almost any peripheral nerve as wella s cranial nerves, particularly the extraocular muscles
What are the treatments for diabetic neuropathy?
- Metabolic control is likely helpful
- Medications for pain like anticonvulsants, antidepressants and narcotic analgesics
- Foot hygiene is imperitive to avoid trophic ulcers of the feet
- Codeine and diphenoxylate for diarrhea
- Support stockings and fluorocortisone or midodrine for postural hypotension
What drugs make you think diabetic neuropathy treatment?
- fluorocortisone or midodrine for postural hypotension
- Codeine and diphenoxylate for diarrhea
- Medications for pain like anticonvulsants, antidepressants and narcotic analgesics
Patients with MG often have what other (gland) signs?
- 85% have thymic enlargement
* 10% have a thymoma
How do you confirm dx of MG?
- Presence of achr antibodies in serum
- Some have MUSK antibody which binds portion of the postsynaptic membrane
- Intravenous injection of edrophonium, an ache inhibitor, temporarily improves strength and corrects the depletion after repetitive nerve stimulation
What are the signs and symptoms of MG?
- Often family history of autoimmune disorders
- Thymic enlargement is common
- Fluctuating weakness and fatigue in cranial, limb or trunk musculature are characteristic
- Ocular symptoms lik eptosis, diplopia and blurred vision
- Facial muscles are weak and speech may become slurred, nasal and hoarse
- Progressive trouble chewing and swallowing and eventual choking and aspiration of food and saliva
- Neck muscle weakness
- Respirator muscle weakness
- Limb muscle weakness is usually not AS big of an issue
What is the treatment for MG?
*great management can lead to a great quality of life, which I found surprising
• Symptomatic relief with oral ache inhibitors like pyridostigmine
• Corticosteroids (prednisone) and other immunosuppressive agents (azathioprine, mycophenolate mofitil) are used
• Temporary (2-3 weeks) dramatic improvemtn is seen following plasma exchange or IV IG infusion
• Thymectomy is recommended for all patients with generalized MG except super young and old
Why is thymectomy recommended inmost MG patients?
• Thymectomized patients need less immunosuppressive medications and experience fewer medication side-effects
What kind of inherited disorders are duchenne and becker dystropy?
- X-linked recessive disorders
* Variety of deletions, duplications and point mutations in the area of the X chromosome coding for dystrophin
What are the molecular genetic ideas for treatment?
- Upreguatin utrophin, a shorter isoform of dystrophin
- Admin gentamycin that helps read through stop codons
- Gene therapy by introduction of healthy gene in stem cells
Are there drug treatmetns for DUD/BD?
- Controversial
- Immunosuppressive medications slow progression slightly
- Use can have complications with growth, weight gain and behavioral problems
How can you determine a carrier status or test the fetus for muscular dystrophy?
- Amniocentesis
- Chorionic villi biopsy
- Peripheral blood of the mother
How can you confirm DUD/BD diagnosis?
- Elevated CK (20-100 fold increase)
* Muscle biopsy shoes characteristic features but aren’t so used b/c less invasiv DNA tests
DUD kills people by what final pathway?
• Weakness of respiratory muscles and heart failure in late teens or early 20s
What do you worry about in boys with DUD that are wheelchair confined?
• Kyphoscoliosis, contractures of all joints, equinovarus deformities of the feet
What does DUD look like?
- Boys have a clumsy waddling gait from the time they first walk
- Proteuberant abdomen results from an accentuation of the lumbar lordosis
- Enlargement of the calves (pseudohypertrophy)
- Tight heel cords with a tendency to toe walk
- Difficulty in rising from the floor (Gower’s maneuver)
- Subnormal intelligence is common
- Eye movements, swallowing and sensation are unaffected
- 9-12 years old, walking is probably unsafe
How does BD differ from DUD?
• Duchenne = DUD • BD = becker ○ Onset is usually later and course is more benign ○ Shorter protein, not fully absent ○ Less mental impairment
