Anterior Horn, PERIPHERAL NERVES, NMJ Disorders Flashcards
ALS*, SMA, polio, West Nile are what class of nerve disorder?
Anterior horn cell disorders
Cervical & lumbar spine; brachial & lumbosacral plexus are what class of nerve disorder?
Radiculopathies and plexopathies
Mononeuropathies* – carpal tunnel, ulnar & peroneal palsy.
Polyneuropathies – genetic (CMT), diabetes, systemic illness, vitamin deficiency, toxic.
Are what type of disorders?
Neuropathies
Myasthenia*, LEMS, botulism, organophosphate poisoning are what class of disorder?
Neuromuscular junction disorders
What are the Myopathies?
Dystrophies*, myositis, metabolic, toxic & endocrine myopathies
UMN vs LMN?
__1__– spastic tone; incr. reflexes; emotional
__2__– decr. tone & reflexes; atrophy
- UMN
- LMN
BOTH: Weakness Rapidity, location, progression Atrophy, hypertrophy, deformities Other Sensory loss; cramps; pain
What is the name of a autoimmune disorder, ab to NMJ acetylcholine receptor?
Myasthenia Gravis
What is the Tx for Myasthenia Gravis?
- Cholinesterase inhibitor → temporary increase in strength and improve decrement following repetitive nerve stimulation
Edrophonium (IV)
Pyridostimine (oral) - Immunosuppression:
Prednisone
Immunosuppressive agents (azathioprine, mycophenolate mofitil) - Plasma exchange, IVIG infusion
- Thymectomy
How do you Dx Myasthenia Gravis?
Diagnosis via presence of ACHR antibodies in serum
What are the clinical features of Myasthenia Gravis?
Diagnosis via presence of ACHR antibodies in serum
What is the disease that is one of the hereditary motor and sensory neuropathies, a group of varied inherited disorders of the peripheral nervous system characterised by progressive loss of muscle tissue and touch sensation across various parts of the body.
Charcot–Marie–Tooth disease
What is Amyotrophic Lateral Sclerosis (ALS)?
Pathologic changes:
Progressive weakness and wasting due to degeneration of brainstem and spinal cord lower motor neurons
Coexisting spasticity and hyperreflexia due to degeneration of upper motor neurons
Hyperreflexia + pathological reflexes (Hoffman, crossed adductor, Babinski)
What are the clinical features of Amyotrophic Lateral Sclerosis (ALS)?
WEAKNESS
Typically sporadic Foot drop Speech may be slurred or spastic Cognitive defects may be seen Normal sensory exam Diaphragm weakness Impaired swallowing → aspiration pneumonia
ALS frequency _____ (increase or decrease) with age?
increases.
ALS affects male more, reasons unknown.
How do you Tx ALS?
Disease-specific: pathogenesis based riluzole: of proven benefit many past and pending trials of agents complementary/alternative medicine (CAM) widely used symptom-specific improve QOL and longevity
How does Becker Muscular Dystrophy different from DMD?
Differs from Duchenne, only in that it has a later onset, has more benign course, and survival is longer.
Mental impairment seen less often.
What is the genetic defect in DMD?
Genetic defect: XR, deletion, duplication, and point mutations on X chromosome.
Only boys.
What are the clinical features of DMD?
- Clumsy waddling gait from first walking.
- Accentuation of lumbar lordosis → protuberant abdomen.
- Calf enlargement.
- Right heel cords, toe walking.
- Gower’s maneuver - trouble rising from floor.
- Subnormal intelligence.
- Eye movements, swallowing and sensation unaffected.
- Increasing proximal weakness with age
- Eventually wheelchair bound, and succumb to respiratory or heart failure by late teens or 20s.
What is the only drug that helps with ALS? Does it treat ALS?
riluzole: of proven benefit many past and pending trials of agents complementary/alternative medicine (CAM) widely used symptom-specific. improve QOL and longevity.
Does not cure!
What is the best drug you can use for muscle cramps? (no longer available in the US)
quinine
dysphagia: ?
Difficulty swallowing
dysarthria: ?
difficult or unclear articulation of speech that is otherwise linguistically normal.
What are the (2) subtypes of Charcot–Marie–Tooth disease?
CMT1A
CMT2
Charcot-Marie-Tooth Disease that presents as slow nerve conduction velocities + demyelinating neuropathy: Hereditary motor and sensory neuropathy.
Is of which subtype?
CMT1A
Charcot-Marie-Tooth Disease that presents as normal nerve conduction velocities + axonal degeneration.
Hereditary motor and sensory neuropathy.
Is of which subtype?
CMT2
What is the genetic defect of Charcot-Marie-Tooth Disease? (2)
- AD (CMT1 and CMT2)
CMT1A = Duplication in DNA containing peripheral myelin protein gene (PMP22) - AR (CMT4)
What are the clinical features of Charcot-Marie-Tooth Disease?
1) Onset of walking normal, but distal (hands and feet) weakness and sensory loss develop slowly over first two decades of life, not usually confined to wheelchair.
2) Impaired/delayed walking as infants, confined to wheelchair later in life.
3) Adult onset, does not appear until age 40
PMP22 gene is ~ with what disorder?
CMT disease
Describe the CMT1A/HNPP mutation?
A 1.4 Mb duplication on chr 17 (PMP22 gene) causes CMT1A.
- Distal weakness, sensory loss and deformities - 10% are de novo mutations.
- Repeats on either side of gene (CMT1A REPS) are hot spot for recombination
- Deletion of the same locus causes HNPP; Focal weakness and sensory loss.
What are the classifications of diabetic neuropathies?
- Sensory or sensorimotor distal polyneuropathy
Stocking/glove numbness and burning pain
Foot drop and weak hand muscles - Autonomic neuropathy
Hypotension, diarrhea, impotence, urinary retention
- Mononeuropathy Cranial nerve (3, 6,7) or peripheral (median, ulnar, peroneal
- Lumbosacral plexopathy
Pelvic girdle pain; asymmetric hip flexor weakness
what is the most common subtype of diabetic neuropathies?
Sensory or sensorimotor distal polyneuropathy.
- Stocking/glove numbness and burning pain. - Foot drop and weak hand muscles
In Carpal Tunnel, what park of the hand is atrophy?
The Thenar (hypothenar)
What is the Tx of diabetic neuropathy?
Good metabolic control of diabetes.
Foot hygiene to avoid ulceration & infection
Night light; well fitting shoes.
Pain management
anticonvulsants, antidepressants, analgesics.
Autonomic symptoms
Diarrhea- codeine, diphenoxylate
Hypotension –fluorocortisone, midodrine
Urinary retention –regular voiding; suprapubic pressure.
Make sure to TAKE CARE OF FOOT!
What is the initial complaint of diabetic neuropathy?
Initial complaints: numbness, burning in feet → spreads up legs, into hands.
- Weakness of foot dorsiflexor muscles → slapping foot drop gait.
- Grip strength and fine hand dexterity diminished
What are the positive exam findings of diabetic neuropathy??
- Pin sensation loss in “stocking-glove” distribution.
- Loss of position, vibration, and light touch.
- Loss of pain and temperature sensation.
- Decreased reflexes.
What is the autonomic dysfunction ~ with diabetic neuropathy?
Postural hypotension, diarrhea, impotence, urinary retention, increased sweating
Explain the effects of cholinesterase inhibitors on nondepolarizing vs. depolarizing neuromuscular blocking agents.
AChEIs can help overcome a block of AChRs by curare (nondepolarizing blocking agent), but AChEIs potentiate effects of succinylcholine (depolarizing neuromuscular blocking agent).
What is a tensilon? And what does a positive tensilon test = ?
Tensilon inhibits the breakdown of acetylcholine so that it accumulates and has a prolonged effect.
Effects include miosis; increased intestinal and skeletal muscle tone; bronchial constriction; bradycardia; increased salivation, lacrimation, and sweating.
Myasthenia gravis.
In Myasthenia gravis, what happens to the thymus?
abnormal hyperplasia of the thymus. (vs. normal involution with age)
involution: ?
the shrinkage of an organ in old age or when inactive, e.g., of the uterus after childbirth.
What is Succinylcholine and its MOA?
Succinylcholine: N-M receptor agonist (2-ACh molecules joined)
Initial stimulation → muscle fasciculations
Depolarization does not allow repolarization and subsequent AP → flaccid paralysis
Flaccid paralysis is POTENTIATED by AChEIs
Explain what happens with brief versus prolonged stimulation of nicotinic cholinergic receptors.
- Prolonged receptor activation prevents the muscle cell membrane from repolarizing, thus preventing subsequent AP → flaccid paralysis.
- Brief stimulation allows depolarization, repolarization, and then finally a subsequent AP to take place.
Plexopathy: ?
Plexopathy is a disorder affecting a network of nerves, blood vessels, or lymph vessels.[1] The region of nerves it affects are at the brachial or lumbosacral plexus. Symptoms include pain, loss of motor control, and sensory deficits
Mononeuropathy: ?
Mononeuropathy is a type of neuropathy that only affects a single nerve.[5] Diagnostically, it is important to distinguish it from polyneuropathy because when a single nerve is affected, it is more likely to be due to localized trauma or infection.
