Compressive and Demyelinating Disorders Flashcards
Demyelination can occur in:
a. peripheral nervous system only
b. central nervous system only
c. both
both
Demyelination in the central nervous system is…
damage to oligodendrocytes
Demyelination in the peripheral nervous system is…
damage to Schwann cells
what is the most common mechanism of injury for demyelination in the CNS?
damage to the processes, usually an autoimmune mechanism (multiple sclerosis)
what is the most common mechanism of injury for demyelination in the PNS?
○ Genetic deficits that impair the ability of Schwann cells to compact or produce myelin sheaths
○ Autoimmune – self-reactive antibodies, antibody complexes, or cytotoxic T-cells damage Schwann cells
what is multiple sclerosis?
immune-mediated disease directed against the CNS -> loss of myelin and eventual loss of axons
is multiple sclerosis more common in men or women?
3x more frequent in women
what is the peak incidence for multiple sclerosis?
between 20-40
true or false? * MS progresses straight to a chronic inflammatory picture with no preceding acute inflammation
true, typical of most autoimmune diseases
what are the 2 phases of MS
○ 1st phase (active plaques): presence of typical leukocytes found during chronic inflammation
▪ Destroy myelin and oligodendrocytes that form it, though new oligodendrocytes can still be generated
Major leukocytes:
* CD4+ Th (likely mostly Th1 and Th17) and B-cells
* Macrophages (recruited and derived from microglia) and cytotoxic T-cells
○ 2nd phase (inactive plaques): loss of axons (and eventually neurons) with limited to no leukocytic infiltration and prominent gliosis
explain active plaques
leukocytes are recruited from the circulation, across the BBB
Helper T-cells initiate an immune response against myelin (MBP which helps to compact the many layers of the myelin sheath)
These helper T-cells recruit other leukocytes into white matter (cytotoxic T-cells, macrophages) and activate them
- Cytotoxic T-cells seem to attack oligodendrocytes
* MBP-specific B-lymphocytes are also recruited into the CNS and produce anti-MBP antibodies – these also seem to help destroy the myelin sheath
what is a flare?
period of worsened neurological symptoms
what causes flares in MS?
Buildup of helper T-cells and cytotoxic T-cells in the CNS that attack white matter components and B-cells that produce myelin-specific antibodies
As flares continue, there seem to be areas where lymphocytes reside “permanently” these are called
lymphocytic follicles
where are the lymphocytic follicles most prominent?
around the meninges and blood vessels
what are inactive plaques
plaques without prominent inflammation
With loss of myelin and oligodendrocytes, axons tend to
degenerate
explain how the axons degenerate
- “destabilization” of action potentials
- Fewer action potentials -> reduced trophic support for neurons – leading to neuronal cell death
- Expression of NMDA receptors on “ naked” axons and calcium-mediated cytotoxicity – glutamate is also toxic to oligodendrocytes
Following demyelination, what happens to allow for action potential conduction
additional sodium channels are redistributed along the axon
what are the most common initial symptoms of MS
- paresthesia’s in one or more extremities, the trunk, or one side of the face
- Weakness or clumsiness of a leg or hand
- Visual disturbances
what is the L’hermitte’s phenomenon
Sensation of an “electrical shock” running down the back and along the limbs
what is Uhthoff sign which is very common in MS patients
a transient worsening of neurologic function (initially described as blurry vision after a hot bath), with heat exposure, physical exhaustion (exercise), infection, or dehydration
what is the symptom and history checklist called for clinical diagnosis of MS
MacDonald’s criteria
what is the treatment of MS
no cure, steroids can be used for acute flares, immunomodulators can be used for chronic treatment
what is the most common progression for MS patients
relapsing-remitting
many relapsing-remitting patients progress to ?
secondary progressive
what does neuropathy mean?
functional disturbance and/or pathological change in the PNS
what does neuralgia mean?
pain in the distribution of a particular nerve, usually in the absence of objective signs
what does neuritis mean?
inflammation of a nerve
what does radiculopathy mean?
pain along a dermatome, implying that the problem is at the level of the nerve root
what does plexopathy mean
neuropathy of the entire plexus
polyneuropathy often presents as:
- symmetrical distal weakness
symmetrical distal sensory loss - hyporeflexia
what does multiple mononeuropathy mean?
involves >1 nerve, but not in a symmetrical fashion
Charcot-Marie-tooth Disease is also known as
hereditary motor and sensory neuropathy (HMSN)
Charcot-Marie-tooth Disease is autosomal dominant or recessive inheritance?
autosomal dominant inheritance
what is the most common inherited neurologic disorder
Charcot-Marie-tooth Disease
what is CMT1
demyelination of peripheral nerves due to abnormal myelin production, damage to nerves, and thickened, palpable myelin sheaths
what is CMT2
axonal death and degeneration without a primary defect in myelin (less frequent)
what is the treatment for Charcot-Marie-tooth Disease
- Massage – ROM to prevent contractures
- Anti-inflammatories, analgesics
what is Guillain-Barre Syndrome (GBS)
Acute onset immune-mediated demyelinating neuropathy
what is the most common cause of acute flaccid paralysis
Guillain-Barre Syndrome (GBS)
Guillain-Barre Syndrome (GBS) typically occurs after what?
an infection
how does Guillain-Barre Syndrome (GBS) develop?
develops rapidly and typically involves predominantly motor symptoms
one of the clinical features of Guillain-Barre Syndrome (GBS) is ascending symptoms. Explain that
weakness starts in the lower limbs, progresses to higher regions of the body
one of the treatments for GBS is plasmapheresis. what is that?
removal of antibodies from the blood
In the peripheral nervous system, compression of a nerve often leads to:
- pain
- loss of motor function
- loss of sensory function
what are the theories of compressive nerve damage?
- Direct mechanical damage to the nerve -> loss of axonal function
- Ischemia- Compression of the vessels in the perineurium -> decreased blood flow and reduced function in the nerve
what is Bell’s Palsy
Idiopathic paralysis of the facial nerve
what is the most common cause of unilateral facial paralysis
Bell’s Palsy
Bell’s Palsy cause was thought to be ?
compression of the facial nerve caused by edema/inflammation caused by herpes virus
T or F: Bell’s palsy tends to self resolve (> 80% of case) over time
true
