Underlying Factors of MS:

Inflammatory Cascade
Clinical Significance of
Demyelinating Lesions of Inflammation
the CNS
Elaine S. Edmonds, MD. PhD
Demyelination
University of New Mexico
Department of Neurology
MS Center Axonal loss

Demyelinating Lesions

Normal spinal cord Spinal cord of MS patient

Generalizations
Demyelinating Lesions
• MS symptoms are highly variable
– Early in the disease symptoms resolve 80% of the time
– Further episodes recur on average 0.5-
0.5-1.2/year
– Most patients present as relapsing-
relapsing-remitting but after several
years become slowly progressive
• The most common sites of initial lesions are optic nerve,
cervical spinal cord and brainstem
• Symptoms of new episodes last >24 hours
• Most (80-
(80-90%) of lesions produce no obvious symptoms
• Pseudoexacerbation-
Pseudoexacerbation- recurrent symptoms due to
increased body temperature (2°
(2° to exercise or infection)
Brain of MS patient
Normal brain

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 Eventual Symptoms
Initial Symptoms of Multiple Sclerosis
of Multiple Sclerosis
• Weakness in one or more limbs 35% • Weakness (spasticity) 80%
• Optic Neuritis 20% • Sensory symptoms 73%
• Paresthesias, sensory symptoms 20% • Visual symptoms 50%
• Diplopia (double vision) 10% Decreased vision or diplopia
• Vertigo 5% • Balance problems (ataxia) 72%
• Urinary symptoms 5% • Bladder symptoms 62%
• Ataxia 3% • Lhermitte’
Lhermitte’s sign 30%
• Fatigue 48%
Monosymptomatic > Polysymptomatic • Cognitive problems 27%

Weakness Associated Signs and Symptoms

• Upper motor neuron weakness with spasticity • Signs
– Lesion in pyramidal or extrapyramidal pathways – Babinski’
Babinski’s sign (extensor plantar reflex)
from the cortex to the lower motor neuron in the – Hyperreflexia
spinal cord – Increased tone
– Pattern can be paraparesis or paraplegia (mc), • Symptoms
monoparesis or monoplegia,
monoplegia, hemiparesis or – Stiffness
hemiplegia – Pain
– Weakness, worse if tired or overheated
• Rarely, lower motor neuron weakness due to
– Extensor or flexor spasms
anterior horn involvement, associated with
– Clonus
atrophy and decreased or absent reflexes

Location of Spinal Cord Lesions

Producing Motor Symptoms Corticospinal and Corticobulbar Tracts

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 Posterior Column-
Column- Medial
Sensory Symptoms
Lemniscal Pathway
• Numbness, tingling, paresthesias and dysesthesias are
common
• Usually occur with other symptoms
• Can affect bowel, bladder or sexual function
• Typically decreased rather than abolished sensation
• Pain (decrease or increase), temperature, tactile,
vibration and position sense can be affected
• Can affect motor function=pseudoweakness
function=pseudoweakness
• Useless hand-
hand- due to loss of position sense
• Lesion in posterior columns of spinal cord
Vibration, position sense, tactile sense

Spinothalamic Pathway Spinal Cord Tracts

Ipsilateral
loss

Ipsilateral
effect

Contralateral
loss
Pain and temperature

Lhermitte’s Sign Ataxia- Cerebellar Signs

• Electric sensation passing from the neck down
the back and legs (arms) on flexion of the neck,
“like a waterfall”
waterfall”.
• Produced by stretching the posterior columns in
the cervical spinal cord
• Occurs with cord compression, radiation
myelopathy and B12 deficiency or demyelination
• Rarely occurs as only symptom (if in isolation,
cerebellar degeneration is more likely)
• Action tremor (UE>LE) rather than resting
tremor is present in MS patients, very disabling
– Plaques in the cerebellum or its connections in the
brainstem
• Gait ataxia can be due to lesions in multiple
sites: spinal cord, brainstem and/or cerebellum

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 Cerebellar Connections Lesions in pons and cerebellum

Cerebellar Input Cerebellar Output Normal Brain Brain of MS patient

MS Lesion Producing Action Tremor Optic Neuritis

• Caused by plaque in optic nerve(s)
nerve(s)
• Accompanied by eye pain esp. 2°2° eye movement
• Decrease in VA (or blindness) increasing over 1-
1-2
weeks, generally improving in 8 weeks
– Recovery is usual although not always complete
• Usually (2/3) no optic disc abnormality initially
– Marcus-
Marcus-Gunn pupil=relative afferent pupillary defect
• Subsequently optic disc pallor is present
• Abnormal visual evoked potentials (not specific)
• Associated with multiple sclerosis
– Risk of developing multiple sclerosis subsequently 40-
40-50%
Normal Brain Brain of MS patient

Optic Neuritis Internuclear Ophthalmoplegia

• Bilateral INO is pathognomonic for MS
– Can rarely be caused by stroke
– Due to a lesion in the medial longitudinal fasciculus
• Connection between the third and sixth nerve nuclei
• Necessary for conjugate eye movements to the opposite
side
• Includes lag or failure to adduct the eye and
nystagmus of the abducting eye on the same side
as the movement with preservation of
convergence

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 Internuclear Ophthalmoplegia Medial Longitudinal Fasciculus
• Bilateral INO is pathognmonic for MS
– Can rarely be caused by stroke
– Due to a lesion in the medial longitudinal fasciculus
• Connection between the third and sixth nerve nuclei
• Necessary for conjugate eye movements to the opposite side
• Includes failure to adduct the eye opposite to the
movement and nystagmus of the abducting eye on the
same side as the movement
• Can be asymptomatic or cause positional diplopia or
oscillopsia

INO Video Transverse Myelitis

• Can be associated with various autoimmune
disorders inc. multiple sclerosis
• Ascending acute or subacute,
subacute, sensory loss (level)
and assymetric paraparesis + bladder symptoms
INO Demo.wmv INO Demo.wmv
• Partial or complete recovery usually in 8-
8-24
weeks
• Increased risk (88%) of multiple sclerosis if CSF
or brain MRI are abnormal, more likely to be a
partial transverse myelitis (assymetric
(assymetric symptoms)

Symptoms of Transverse
Myelitis
Loss of proprioception, vibration,
position sense, tactile (B- loss of
bladder control and sensory level) • Thank you for
your attention
Weakness and spasticity
(B- paraparesis, loss of
bladder control)

Loss of pain and

temperature
(B- sensory level)

Other symptoms: band-like constriction around trunk or extremities,

back or radicular pain