Multiple Sclerosis/ demyelination Flashcards
MS
General
life expectancy 7-14 year rreduction
>1/2 death related to complications
most frequesnt source of permanent disability in young adults aside from trauma.
The most common immune-mediated inflammatory demyelinating disease of the central nervous system
Females > Males
Mean age of onset 28-31
Possible genetic susceptibility
Familial
3-23%
Environmental
Viral
Vitamin D deficiency
Geography
MS
Pathophys
Characteristic feature
presence of focal demyelinated plaques in CNS
Optic nerve
Spinal cord
Brainstem
Cerebellum
Juxtacortical/ periventricular white matter
MS
Dx
Multiple sclerosis is a clinical diagnosis
Good clinical history
Physical Examination
Imaging (MRI)
MS
Clinical manifestations
No unique clinical findings
Presenting symptoms
Monosymptomatic = Single lesion
Polysymptomatic = > than 1 lesion
Typical presentation
Young adult
Clinically distinct episode(s) of CNS system dysfunction
Partial or full resolution
MS
S/Sx
Numbness/tingling
Tightness
“MS hugs” - chest discomfort
“Anaconda sign” - constricting sensation
Coldness
Swelling of limbs/trunk
Intense itching sensation
Usually unilateral and in cervical dermatomes
MS
Neurologic Symptoms
Cognitive impairments
Cognitive impairment (common)
Difficulty with attention
Short term memory
Speed of information processing
Abstract conceptualization
Frank dementia < 5%
MS
Unilateral Optic Neuritis
Painful monocular vision loss
visual blurring
partial vision loss
90% regain vision within 2-6 months
MS
pain symptoms
Paroxysmal (sudden) pain
Persistent pain
burning
cold dysesthesias
Musculoskeletal
Soft tissue
MS
Heat Sensitivity
Uhthoff syndrome
Uhthoff phenomenon: increase in body temp worsens symptoms
More than half of patients
Small increases in body temperature temporarily worsen symptoms
Conduction block in central pathways as temp increases
demyelinated nerves occur faster
MS
Genitourinary Symptoms
Urge incontinence
Overactive bladder
Functional bladder outlet obstruction
Symptoms
Hesitancy
Interrupted stream
Incomplete emptying
Erectile dysfunction
Decreased libido
MS
GI Symptoms
Urge incontinence
Constipation
Poor evacuation
Incontinence
MS
Neurologic PE
Signs
Paraplegia/paraparesis
lesions in the descending tract of spinal cord
Spasticity
Tonic: resistance to movement
Phasic: involuntary jerks and spasms
Diminished deep tendon reflex
lesions interrupting the reflex arc
Lhermitte Sign
Electric shock shooting down the spine or into the limbs most often after flexion of the neck
Intention tremors
45% of MS patients
Difficulty with coordination
Dysmetria: inability to control the distance, speed, ROM necessary to perform coordinated movements
Hypotonia: weak muscle tone
Gait disturbances
Cerebellar dysarthria (eg, scanning speech)
MS
Sensory Findings
Vibration/joint position sense impairment
Patchy areas of reduced pain and light touch perception in limbs/trunk
Brown-Sequard syndrome: weakness or paralysis and proprioceptive deficits ipsilateral to lesion with loss of pain and temp sensory contractural to lesion.
Testing sensation with sharp object, feeling is increased or spreads like a ripple effect
Contralateral weakness
MS
Ocular Findings
Optic neuritis
Afferent pupillary defect (Marcus-Gunn pupil) with swinging flashlight test (defect is in retina, optic nerve, chiasm, or anterior optic tract)
Disc edema if involves head of the optic nerve
MS
Abnormal eye movements
Internuclear ophthalmoplegia
Pendular nystagmus
MS
MRI brain
Diagnostic image of choice
Hyperintense white matter lesions on T2 sequence
Plaques
Ring enhancing
Ovoid
“Black hole” lesions
Severe demyelination and axonal loss
MS
MRI Spine
Less likely to be asymptomatic
Size ≥3 mm but < 2 vertebral segments in length
Occupy only part of the spinal cord
Little to no cord swelling
Focal
Clearly delineated
Well circumscribed
Chronic lesions
Smaller
Well-defined margins
Acute lesions
Larger
Ill defined
More gadolinium uptake
Dissipates over a few weeks
Rarely up to 8 weeks
MS
Lumbar Puncture
If clinical picture and imaging insufficient
Atypical clinical or imaging features
Atypical population (children and older adults)
MS
Evoked Potentials
Electrical events generated in the CNS by peripheral stimulation of a sensory organ
Detects subclinical abnormal CNS function
Define anatomic site of lesion not easily visualized by imaging
optic nerve
MS
Optical Coherence Tomography
Uses infrared light waves that reflect off the internal microstructure of biological tissue to produce images
Noninvasive way to image the retina at high resolution
Measure thickness of retinal nerve fiber layer
85% are reduced
MS
Classifications
- Two main classifications
Relapsing-remitting MS
Progressive MS
Primary
Secondary - Several additional classifications
Clinically isolated syndrome
Radiologically isolated syndrome
Relapsing Remitting MS
general
80-95% of patients
Attacks with full or incomplete recovery
Frequency varies
Average 0.4-0.6 relapses/year
Minimal disease progression between relapses
Secondary progressive
General
Initial relapsing-remitting course followed by gradual worsening with or without occasional relapses, minor remissions and plateaus
Typically, 10-20 years from disease onset
90% RRMS will develop within 25 years
retrospective Dx
no clinical criteria
Primary progressive
general
Progressive accumulation of disability from onset with occasional plateaus, temporary minor improvements or acute relapses
10% of cases
Mean age of onset: 40 years
typical presentation
Spinal cord syndrome worsening over months to years
Clinical Dx
Clinically Isolated Syndrome(CIS)
General
First clinical episode
Resembles typical MS relapse
No known history
Does not meet diagnostic criteria
Radiologically Isolated Syndrome(RIS)
general
MRI findings suggestive of MS
(usually unrelated reason)
No signs or symptoms
No history of MS
Risk factors for conversion to symptomatic course
Male
Age < 37
Spinal cord lesion
McDonald Criteria
Don’t need to know
The criteria assign diagnostic confidence as follows:
The diagnosis of MS is given if the McDonald criteria are fulfilled and there is no better explanation for the clinical presentation
The diagnosis of possible MS is given if MS is suspected by virtue of a CIS but the McDonald criteria are not completely met
The diagnosis is not MS if another diagnosis better explains the clinical presentation
Clinical Measurement of Disability
Kurtzke disability status scale (DSS)
Expanded disability status scale (EDSS)
Typically used in clinical trials (next slide)
Patient-determined disease steps (PDDS) scale
Utilizes patient reported outcomes to determine disability score
Prognostic Indicators of Disability
Lesion load on MRI
Brain atrophy affecting gray and white matter
Male
Presentation >35yo
PPMS
May be more related to age than on initial course (regardless of subtype)
Bowel/bladder symptoms at onset with incomplete recovery (RRMS)
Short interval between 1st and 2nd attack
Polysymptoms at diagnosis=shorter time to progressive disease
MS
Tx strategies
Treatment strategies:
Treatment of acute exacerbations with corticosteroids
Reduction of biologic activity with disease-modifying medications
Symptom management
Rehabilitation and psychosocial support
MS
Acute attack
Criteria
Episode of focal neurologic disturbance >24 hours
Preceding clinical stability for ≥30 days
Without an alternate explanation
Consider MRI brain
Assess for new lesion
Goal of treatment is to lessen time to recovery
MS
Acute Treatment
Glucocorticoids
3-7 day course of IV methylprednisone 500-1000mg with or without a short prednisone taper
OR
3-7 day course of oral prednisone 625 to 1250mg daily with or without a short taper
Corticotropin injection gel (bovine or porcine ACTH)
More expensive
Reserved for those with poor IV access or who cannot tolerate high dose glucocorticoids
Plasma exchange - For those that fail glucocorticoids
Long term Treatment: RRMS, SPMS, CIS
Disease modifying therapy
Decrease relapse rate
Partially effective
Slower accumulation of brain lesions on MRI
Unclear if reduces disability progression
There is no cure
Continue indefinitely unless SE intolerable
MS
Intravenous Therapy:
Monoclonal Antibodies
Natalizumab (Tysabri)
Ocrelizumab (Ocrevus)
Alemtuzumab (Lemtrada)
Natalizumab
MOA
Associated with diminished migratory capacity of immune cells and a prolonged decrease in lymphocyte counts in CSF
Natalizumab Side effects
Headache*
Flushing *
Erythema*
Nausea *
Dizziness*
*During infusion
Fatigue
Infections
UTI and lower respiratory tract infections
Arthralgia
Progressive multifocal leukoencephalopathy (PML)
Progressive Multifocal Leukoencephalopathy
general
Rare potentially fatal neurologic condition
Demyelination of the subcortical white matter, gray matter, and cortex
Caused by JC virus (JCV) infection
Natalizumab Black box warning
dont use with history of Progressive Multifocal Leukoencephalopathy
Oral therapies
S1P receptor modulators
Fingolimod (Gilenya)
Siponimid (Mayzent)
Ozanimid (Zeposia)
Ponesimod (Ponvory)
Sphingosine 1-phosphate (S1P) receptor modulators
MOA
Mechanism of action: sphingosine analogue that modulates the S1P receptor and thereby alters lymphocyte migration, resulting in sequestration of lymphocytes in lymph nodes
S1P
Contraindications and SE
In past 6 months
1. Myocardial Infarction (MI) or unstable angina
2. Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
3. Heart failure
History of 2nd or 3rd degree heart block
Anti-arrhythmic drugs
Prolonged QT interval ≥500 ms on EKG
Side effects: HA, elevated LFTs, diarrhea, cough, flu like symptoms, arthralgias, bradyarrhythmia, macular edema
S1P Receptor ModulatorsSide Effects
Headache
Elevated LFTs
Diarrhea
Cough
Flu
Arthralgias
Bradyarrhythmia
Macular edema
Opportunistic infections
Injectable Tx
Ofatumumab
Interferons
monitoring on therapy
Refractory disease:When to consider treatment change
