Neuromuscular Flashcards
What is the general structure of peripheral nerves and how do they interact with muscle fascicles?
- conduct stimuli to and from spinal cord
- Peripheral nerve fascicles interact with muscle fascicles at the neuromuscular junction
- Degree of innervation corresponds to complexity of movements of innervated muscle group
Unmyelinated vs. myelinated nerves in the PNS
-Unmyelinated nerve fibers
Small diameter fibers (.2-.3 microns)
Intermingled with myelinated nerve fibers
Myelinated nerve fibers
-Schwann cells produce myelin sheaths with one cell providing all myelin within each internode
-Node of Ranvier: space between internodes
-Larger diameter fibers (2-15 microns)
-Thickness and length of internodes varies with axon size
What is a normal contractile unit composed of?
- intermeshed actin and myosin fibrils
Z band is junction between sarcomeres (dark band within pale I band)
A band is central band
I band is pale band that spans two sarcomeres (represents region of contraction-varies in size)
What’s the difference between type I and II skeletal muscle fibers? How are they staining-wise?
Type I mediate tonic contraction
-ATPase staining: dark at pH4.2 and light at pH9.4
Type II fibers mediate phasic contraction
-ATPase staining: light at pH4.2 and dark at pH9.4
What determines Type I vs. Type II?
Motor neuron that innervates muscle fiber determines type I vs. type II phenotype
Normally they are evenly intermixed in the fascicle
What are the classic features of neuromuscular disease?
Muscle weakness is hallmark:
- Specific symptoms may suggest etiology
- Poor dentition related to oro-facial weakness, impaired swallowing and general poor hygiene
What are the different etiologies of neuromuscular disease?
- Peripheral nerve disease: Distal muscle weakness with sensory deficits
- Myopathies (primary muscle disorders): Proximal muscle weakness without sensory deficit
- Neuromuscular junction disease: Easy fatigability progressing to severe weakness and potential paralysis
- Upper motor neuron disease: Weakness with increased muscle tone, hyper-reflexia and pathologic reflexes (Babinski, etc)
What are the four types of neuromuscular injury patterns?
Segmental demyelination
Axonal degeneration with muscle atrophy
Nerve regeneration and reinnervation
Muscle fiber damage
Describe the neuromuscular injury battery of SEGMENTAL DEMYELINATION–what causes an “onion bulb”?
- Patchy involvement of internodes
- Schwann cell death and myelin resorption
- Endoneurial derived cells differentiate into replacement Schwann cells
- Remyelination produces thinner, shorter internodes
- “Onion bulb” formation occurs after repeated episodes of remyelination
Describe the neuromuscular injury of AXONAL DEGENERATiON
-Traumatic injury, disuse or intrinsic neuronal disease
Wallerian degeneration: Characteristic breakdown of distal axon
-Atrophy of muscle fibers:
-Decreased size and increased angularity (often triangular) of involved muscle fibers increase of endomysial tissue
–Myelin ovoids: abundant broken down myelin
—Preferential type II fiber atrophy in disuse
Describe the neuromuscular injury of NERVE/AXON REGENERATION AND REINNERVATION. What characterizes these?
- Atrophied muscle fibers reinnervated by sprouting of new nerve endings from neighboring nerve fiber
- Type grouping: clusters of single type of muscle fiber
- —Phenotype of muscle fiber can change depending on nerve that innervates it - ———Thin axons and myelin sheaths characterize regenerative axons
Describe the neuromuscular injury of MUSCLE FIBER DAMAGE
- Segmental Necrosis: Fragmentation of fibers and macrophage infiltration of fascicles
- Regenerative changes: Internalized nuclei (enlarged; prominent nucleoli); Muscle fiber splitting and cytoplasmic basophilla
- Vacuolization and intracytoplasmic deposits
- Hypertrophy (increased fiber size) may occur in extreme exercise and some diseases
What are the types of peripheral nerve disease generally?
Inflammatory neuropathies Infectious polyneuopathies Hereditary neuropathies Acquired metabolic and toxic neuropathies Traumatic neuropathies
Give an example of an inflammatory peripheral nerve disease. What is the histology?
Guillain-Barre Syndrome (GBS)–Acute and self-limited
- Usually preceded by virus which is resolved prior to GBS
- Ascending paralysis with minor sensory deficits
- Isolated increase of CSF protein
Histology: Segmental demyelination, peripheral nerve inflammation
-T-cell destruction of peripheral nerve myelin sheath
-Circulating anti-myelin antibodies have been detected
Treatment: Plasmapheresis (Ab clearance)
Give an example of hereditary motor and sensory neuropathy type 1 (HMSN1).
Charcot-Marie-Tooth, hypertrophic
Characteristic nerve and muscle histology:
-Grouped muscular atrophy
-Segmental demyelination with prominent onion bulbs
- Autosomal dominant: PMP-22 (myelin specific protein), chromosome 17
- Onset in adolescence/early adulthood & slow progression; lower extremities only; normal life expectancy
What are the dental features of HMSN1/Charcot-Marie Tooth?
Damaged oral tissues and tongue due to biting without pain
Oral shields can be employed to reduce trauma
Give an example of hereditary motor and sensory neuropathy type 2 (HMSN2).
- Charcot-Marie-Tooth, neuronal (the HMSN1 is heterotrophic)
- Autosomal dominant with genetic abnormality that differs from HMSN I
- Rare segmental demyelination and onion bulbs
Give an example of hereditary motor and sensory neuropathy type 3 (HMSN3).
Dejerine-Sotas
- Autosomal dominant
- Presentation in infancy with progression to severe neurological impairment
- Prominent demyelination and onion bulbs (obvious palpable hypertonic nerves)
What are some other etiologies of peripheral neuropathies?
Infectious – Varicella Zoster Virus/VZV (shingles)
Toxic/Metabolic:
- Adult onset diabetes mellitus
- -Neuropathies of Malignancy – Small cell carcinoma of the lung
Traumatic neuroma
Give some examples of muscular diseases
- Inflammatory Myopathies (polymyositis and dermatomyositis)
- Muscular dystrophies – Hereditary myopathy
- X-linked (Duchenne’s and Becker’s)
- Autosomal dominant (Myotonic dystrophy)
- Toxic myopathies (thyroid, EtOH and drugs)
What is polymyositis?
- inflammatory myopathy
- Insidious onset, chronic course
- Symmetric proximal weakness
- HIV associated polymyositis (same course and histology)
Describe dermatomyositis
- inflammatory myopathy
- Skin rash precedes weakness with acute progression
- May be associated with connective tissue disorders or malignancy
Dental implications of dermatomyositis
Gum margin involvement with capillary dilatation and inflammation
Late calcinosis develops in two-thirds of patients
Describe the 2 types of X-linked muscular dystrophies
Both Equally effects type I and II fibers; Dense fibers
Duchenne’s M.D. (most severe)
- Normal infancy with onset between 1-5 years of age and progression to death 20-25 years of age
- Weakness in pelvic and shoulder muscles
- Heart involvement with failure and arrhythmias
- Mental impairment (etiology unclear)
Becker’s M.D. – Less severe: later onset, normal life exp, no heart involvement
