neurology: demyelinating illnesses in CNS Flashcards
what do demyelination diseases look like in the CNS?
damage to oligodendrocytes or their processes that myelinate axons –> usually autoimmune
what do demyelination diseases look like in the PNS?
damage to schwann cells from genetic deficits that impair the ability of schwann cells to produce myelin sheaths or autoimmune mechanisms
what is multiple sclerosis?
immune-mediated diseases directed against the CNS –> loss of myelin and eventual loss of axons
what are common findings of MS?
- chronic inflammatory findings
- white matter lesions throughout the brain and spinal cord
- pathological specimens are firm and indurated in areas of white matter loss
what is the most common demyelinating illness?
MS –> 3X more common in women, begins during adulthood
what is the etiology of MS?
- polygenetic etiology: involved genes are HLA2, IL2, IL7, IL17
- link to viral infections such as EBV (because of B-lymphocytes going into CNS due to virus)
- sun exposure and low levels of vitamin D
- other autoimmune diseases
what is the pathogenesis of MS?
2 phases:
1) active plaques: presence of typical leukocytes found in chronic inflammation (CD4, Th1, Th17, B-cells, macrophages and cytotoxic T-cells) –> destroys myelin and oligodendrocytes but more can still be produced
2) inactive plaques: loss of axons and eventually neurons with limited to no leukocytic infiltration and prominent gliosis
what are the characteristics of MS plaques?
Multiple well-circumscribed, irregularly shaped plaques that are firmer than the surrounding tissues
Commonly occur adjacent to the lateral ventricles, optic tracts, brainstem, cerebellum,
spinal cord
More prominent in areas rich in white matter
Over time, a degree of cerebral atrophy may be
noted
what are the active plaques in MS pathogenesis?
- leukocytes cross the BBB to the CNS
- helper T-cells initiate immune response against myelin
- helper T cells recruit other leukocytes (cytotoxic T-cells, macrophages) into white matter and activate them
- cytotoxic T-cells attack oligodendrocytes
- myelin basic protein specific B-lymphocytes are recruited into CNS to produce anti-MBP antibodies that destroy myelin sheath
what stains are used in MS?
Hematoxylin and eosin (H&E) stain shows perivascular infiltration of inflammatory cells
These infiltrates are composed of activated T
cells, B cells and macrophages
what is an MS flare?
flare= period of worsened neurological symptoms
what happens during an MS flare up?
build-up of helper T-cells and cytotoxic T-cells in the CNS that attack white matter components and B-cells that produce myelin-specific antibodies
In between flares, fewer chronic inflammatory cells detected
what are lymphocytic follicles?
areas where lymphocytes reside permanently –> prominent around the meninges and blood vessels
what is the pathogenesis of inactive plaques?
inactive plaques= plaques without prominent inflammation
axons degrade without myelin and oligodendrocytes –> destabilization of AP –> neural cell death
after demyelination, more sodium channels are redistributed along the axon, allowing AP conduction –> continuous conduction of AP requires more ATP –> neural metabolism consequences
what are common initial symptoms of MS?
Paresthesias in one or more extremities, the trunk, or one side of the face
Weakness or clumsiness of a leg or hand
Visual disturbances:
▪ Partial loss of vision and pain due to optic neuritis
▪ Diplopia
▪ Scotomas
▪ Nystagmus and dizziness
what are cognitive impairments of MS?
fatigue, depression, impaired cognition
what are sensory symptoms of MS?
paresthesia and loss of sensation, L’hermitte’s phenomenon (electrical shock sensation), pain
what are motor symptoms of MS?
bilateral, spastic weakness mostly in lower limbs, increased DTR, charcot triad (dysarthria, nystagmus, tremor), slurred speech
what are brainstem and spinal cord findings related to MS?
dizziness, bladder dysfunction, constipation, erectile dysfunction/genital anesthesia, urinary and fecal incontinence in advanced cases
explain heat and activity intolerance in MS?
May be linked to “action potential destabilization”
▪ Uhthoff sign – hot environment or shower –> blurry vision
▪ a transient worsening of neurologic function (initially described as blurry vision after a hot bath), with heat exposure, physical exhaustion (exercise), infection, or dehydration is very common in MS patients.
▪ Heat causes transient worsening of many symptoms of MS and can cause fatigue. Temporary, short-lived (less than 24 hours), and stereotyped worsening of neurological function among multiple sclerosis patients in response to increases in core body temperature.
how is MS diagnosed?
- macdonald’s criteria
- characteristic lesions on brain scan and spinal MRI (not specific but sensitive)
- presence of certain types of antibodies in CSF
what is Macdonalds criteria for MS?
documentation of 2 or more episodes of symptoms and 2 or more signs
- pathology in anatomically non-contiguous white matter tracts of the CNS
- symptoms must longer than 24 hrs
-must occur as distinct episodes that are separated by a month or more
what is the treatment for MS?
- no cure
- steroids for acute flares
what is the progression of MS?
Relapsing-remitting: most common
* 90% of patients first presenting with MS
Secondary progressive
* About 1% of MS patients develop secondary progressive MS/year
Primary progressive
* 10% of patients first presenting with MS
prognosis is better for relapsing-remitting and worse for primary progressive
Many relapsing-remitting patients progress to
secondary progressive
Secondary proressive is often less responsive to
immunomodulatory drugs
what is neuropathy?
functional disturbance and/or pathological change in the PNS
what is neuralgia?
pain in the distribution of a particular nerve, usually in the absence of objective signs
what is neuritis?
inflammation of nerve
what is radiculopathy?
pain along a dermatome, implying that the problem is at the level of the nerve root
what is plexopathy?
neuropathy of the entire plexus
what do peripheral neuropathies present as?
symmetrical distal weakness, symmetrical distal sensory loss and hyporeflexia
what is multiple mononeuropathy?
involves more than 1 nerve but not symmetrically –> due to toxins, diabetes, AIDS, chronic inflammatory diseases
what is charot-marie-tooth disease?
- hereditary motor and sensory neuropathy (HMSN)
- autosomal dominant inheritance (penetrance is variable)
- most common inherited neurologic disorder
what is the pathophysiology of charcot-marie-tooth disease?
CMT1 – demyelination of peripheral nerves due to abnormal myelin production, damage to nerves, and thickened, palpable myelin sheaths
▪ Proteins involved in myelin compaction are
defective, resulting in demyelination/
remyelination cycles
CMT2 – axonal death and degeneration without
a primary defect in myelin (less frequent)
what is the clinical presentation of Charcot-marie-tooth disease?
- sensory and motor symptoms
- slowly progressive distal symmetric muscle weakness and atrophy (champagne bottle legs): diminished DTRs, foot drop, pes cuvas with hammer toes
- proprioception and touch are affected (less pain and temp)
-nerves become large and palpable
how do you diagnose CMT?
- nerve biopsy and nerve conduction studies, physical exams, history
how is CMT disease treated?
massage, anti-inflammatories, analgesics
what is the prognosis of CMT disease?
Most have normal life expectancy
▪ Involvement of phrenic nerve or cranial nerves is very rare
▪ For reasons not well understood, usually exclusively affects the lower leg
what is guillain-barre syndrome?
Acute onset immune-mediated demyelinating neuropathy
* Uncommon disease, but most common cause of acute flaccid paralysis
what is the pathogenesis of GBR?
- after an infection (Campylobacter jejuni,
cytomegalovirus, Epstein-Barr virus, and
Mycoplasma pneumoniae, or prior vaccination are shown to be associated) - T-lymphocytes that presumably recognize
myelin cause a segmental demyelination
▪ Macrophages are also found within lesions and are thought to aid destruction of nerves
▪ Antibodies also likely mediate some damage;
plasmapheresis improves symptoms
GBS is simple terms:
The body’s immune system begins to attack the
body itself
* The immune response causes a cross-reaction
with the neural tissue.
* When myelin is destroyed, destruction is
accompanied by inflammation.
* These acute inflammatory lesions are present
within several days of the onset of symptoms.
* Nerve conduction is slowed and may be
blocked completely.
* Even though the Schwann cells that produce
myelin in the peripheral nervous system are
destroyed, the axons are left intact in all but the
most severe cases.
* After 2-3 weeks of demyelination, the Schwann
cells begin to proliferate, inflammation
subsides, and re-myelination begins.
how is GBS diagnosed?
history, physical, EMG, nerve conduction study
how is GBS treated?
can progress to loss of function including cervical spinal cord –> protect airway, plasmapheresis (removal of antibodies), IV immunoglobulins
- prognosis is good if pt survives initial disease
what is compressive neurological damage?
in the PNS, compression of a nerve leads to pain, reduction of function (motor, autonomic, sensory)
general pathophysiology of compressive neurological damage
1) direct mechanical damage tot he nerve –> loss of axonal function (crush injury)
– less severe –> compressive defects in axonal
transport
– severe –> nerve death
2) ischemia: compression of the vessels in the perineurium –> decreased blood flow and reduced function in the nerve
– nerve usually survives unless compression is severe
– likely most important mechanism of injury
– Impingement of the nerve ! inability to “glide” along its course may explain symptoms that are dependent on position
what is bell’s palsy?
Idiopathic paralysis of the facial nerve, most common cause of unilateral facial paralysis
Thought to be compression of the facial nerve caused by edema/inflammation caused by herpes virus
▪ Herpes virus normally lies dormant in the cell body of neurons
what is the pathophysiology of bell’s palsy?
Herpes virus reactivation –> Edema of the facial nerve (CN7) during inflammation –> compression of the nerve in the very narrow compartment of the petrous portion of
the temporal bone where the nerve runs
* Studies suggest that this compartment is more narrow on the affected side than on the contralateral side
what is the clinical presentation of bell’s palsy?
Acute onset of unilateral upper and lower facial
paralysis (over a 48 hour period)
* Posterior auricular pain, earache
* Decreased tearing or epiphora
* Hyperacusis
* Taste disturbances
* Otalgia
* Poor eyelid closure
what is the diagnosis of Bell’s palsy?
signs and symptoms
what is the treatment for bell’s palsy?
steroids and antivirals have limited value –> surgery in stubborn cases
tends to resolve resolve in 80% of cases
