ANTONIO, DESIERY K.

BSRT 2 May 10, 2020

MULTIPLE SCLEROSIS
Part I: Case Report Review
A) Patient Information:
SCORE:48/50
CONTENT: 24/25 ORGANIZATION: 15/15 MECHANICS: 9/10
COMMENTS: There are some grammatical lapses especially in the case part. The case was
adequately presented except for some lacking findings in the clinical part. Discussion is
excellent. Great Work!

A 35 y/o Caucasian female and professional oboe player complains difficulty reading musical
scores and even playing the instrument unlike before. Six years ago, patient had incidence of loss of
vision in her left eye (visual acuity:10/100) and was diagnosed with optic neuritis (inflammation of optic
nerve). She Underwent MRI scan that revealed multiple lesions in the white matter of her brain. After 5-
day course of IV corticosteroids, her vision returned to normal after 3 weeks and she was advice
(advised) to return for frequent neurologic examination. Three years ago, she experienced weakness
of muscles on the left side of the face and with a repeated a repeat MRI scan found new lesions with
abnormal CSF findings that lead to the diagnosis of MS (see diagnostic assessment for details). After
another 5-day course IV corticosteroids therapy and weekly intramuscular injections of interferon (IFN)-
β, patient’s symptoms improved until she began experiencing the abovementioned again. Family
history reveals that her mother had severe MS and was permanently disabled. Could have improved
the presentation of the history using proper presentation format.
A
B
B) Clinical Findings:
Patient feels weakness in left leg and hand with noted slurred
speech, nystagmus (rapid uncontrolled horizontal jerking eye movements
when attempting to fix the gaze on something e.g., image A) and ataxia
(uncoordinated movement e.g., image B). Other pertinent findings?

C) Diagnostic Assessment
C.1. Results of 6 years ago (initial occurrence) and 3 years prior to patient’s admission.
Three-dimensional magnetic resonance images of the brain.
Left; patient’s MRI result 6 years ago revealing multiple lesions.
Right: patient’s result 3 years ago presenting new lesions at the
left middle cerebellar peduncle and pons.
The technique used causes fluid to appear white. The lateral
ventricles in the middle of the brain scan and the sulci of the
cerebral cortex around the edge appear white as a result of
normal cerebrospinal fluid. The white spots, which are due to
edema fluid and decreased myelin, are MS lesions.

Two computer-generated images of MRI scans of the brain, shown at the

same point.
The lateral and middle ventricles appear in purple. Old MS lesions appear yellow
green. A new, gadolinium-enhanced, lesion appears orange.

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ANTONIO, DESIERY K. BSRT 2 May 10, 2020

CSF is also obtained via lumbar puncture contained 28 mg dl–1 protein (normal) and 8
lymphocytes ml–1 (normal 0–3 ml–1). Protein might be normal but the IgG content is raised. At this
point,a firm diagnosis of MS is made.

C.2. Current diagnosis

Relapse-Remitting Multiple Sclerosis

D) Therapeutics, Patient Outcome and Follow-up.

Patient was given another course of corticosteroids,
after which her symptoms improved, but 8 months later they
recurred. The injections of IFN-β were stopped and she was
put on high doses of cyclophosphamide & corticosteroids
at monthly intervals. After 3 months of this therapy, the
cyclophosphamide and corticosteroid injections were gradually
reduced to every 12 weeks. Her neurological examination Lesion has diminished in size after
aggressive immunosuppressive therapy
became normal and no new lesions were observed on
gadolinium-enhanced MRI.

Supplementals:
What’s the significance of increased lymphocytes in CSF in the diagnosis of MS patient?
Lymphocytes are part of the immune system and on this case they’re the ones causing the
demyelination (dectruction of myelin sheath) of neurons which is the primary feature of MS.
What’s the rationale behind the relapse of the disease?
It is due to remyelination, meaning body cell’s attempt to fix the damaged myelin sheath, however not
permanently because of the high vulnerability of oligodendrocytes (myelin sheath producer).
Px was given corticosteroids, IFN- β & cyclophosphadime, what’s the aim of the therapy?
IFN-B, Corticosteroids and cyclophosphamide (a powerful cytotoxic drug) inhibit T-cell proliferation and
thus interfere with the secretion of cytokines that drive the inflammation and further T-cell activation
Why was IFN- β stopped on the course of therapy?
Interferon beta is ideal for long term therapy and on the patient’s case, she was doing poorly on therapy
(note the relapse just after 8 months) that’s why alternative treatment was considered= high dosage of
corticosteroid and cyclophosphadime.
Geha, R., & Notarangelo, L.( 2016).Case studies in immunology: A Clinical Companion. (7th ed). USA: Garland Science.
Images: https://www.allaboutvision.com/conditions/nystagmus.html
https://www.protokinetics.com/2019/12/18/common-gait-deviations-ataxic-gait/
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ANTONIO, DESIERY K. BSRT 2 May 10, 2020

Part II: Discussion

A) Epidemiology:
 2-3 times more common in women than men
 Age of onset; 2nd -4th decades of life (slightly later in men than women)

Taken at www.thelancet.com

 Geographically, more prevalent in northern and southernmost latitudes, hence, higher risk to
Caucasians than Africans, Asians and areas marked above.
Corresponding rationale: Vitamin D deficiency (see pathology for more info)
 Vitamin D deficiency is associated with an increase in MS risk. At high latitudes, there’s often
insufficient amount of UVB radiation reaching the earth’s surface (esp. during winter months).
UVB radiation from the sun is essential for biosynthesis of Vitamin D.
*Case recall: patient is a 35 y/o Caucasian female

B) Pathology:
Etiology:
 Genetic predisposition
 Cigarette smoking; lung was identified as a critical site for activation of pathogenic T-cells
 Epstein-Barr virus (EBV) exposure after early childhood; the disease can cause
abnormal increase of infectious monocytes in the blood that would lead to MS, supported by
many epidemiologic and laboratory studies but not established yet.
 Vitamin D deficiency; studies showed that Vit D inhibits pro-inflammatory activity of T-cell
and their production of cytokines which are responsible for demyelination.
*Case recall: patient has family history of MS

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ANTONIO, DESIERY K. BSRT 2 May 10, 2020

CD4 T-cells get through the

Pathophysiology: Blood Brain Barrier (BBB) and
is activated by myelin sheath
*Case recall: patient’s CSF
findings contain elevated level
of lymphocytes Activation prompts the release
of cytokines

Dilate the BBB vessel

Damage oligodendrocytes (inflammation) allowing more
immune cells to enter

B cells Macrophages

Produce antibodies marking the Utilize those markers to engulf

myelin sheath & destroy oligodendrocytes

Gliosis (plaques or scarring)

Regulatory T-cells comes in &

inhibit other immune cells (e.g.,
macrophages and T-cells)
Remission
period
Reduction of inflammation
(symptoms
become
Healing of oligodendrocytes normal )
and reconstruction of myelin
begins (remyelination)

Oligodendrocytes soon dies

due to vulnerability to oxidative Relapse
damage period
(symptoms
Remyelination stops, continue worsen )
damage

Irreversible damage of neuron Loss of axons

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ANTONIO, DESIERY K. BSRT 2 May 10, 2020

Clinical Signs and Symptoms:

Sensory Paresthesia (e.g., tingling, prickling sensations, “pins and needles,” or painful
burning) or Hypesthesia (e.g., reduced sensation, numbness, or a “dead” feeling)
Visual Optic neuritis* (presents as diminished visual acuity, dimness, or decreased color
perception in the central field of vision) and diplopia
Motor Weakness of limbs and face*, Loss of tendon reflex, Muscle spascity
Ataxia* (lack of voluntary coordination of mucles e.g.eye movement, speech, walk)
Psychiatric Depression & loss of cognitive ability (memory and problem solving skills)
Genitourinary Bladder dysfunction, Sexual dysfunction and constipation
Others Uhthoffs symptoms (symptoms appear upon elevation of body’s core
temperature like sudden blurring of vision while taking a hot shower )
Lhermittes symptoms(an electric shock–like sensation, typically during flexion
or other movements of the neck, that radiates down the back into the legs & rarely
in arms )
*case recall

 Patient is otherwise asymptomatic and sometimes post-mortem

 Diagnosis is uncertain during early onset but could develop 1-10 years or longer.
Clinical Course

A B C

A) Relapse-Remitting MS (RRMS); most common, presence of “attacks”. Symptoms worsen

(relapse) then normalizes (remission) but later worsens and doesn’t remit completely.
B) Secondary Progressive MS (SPMS); initially behaves like RRMS then progressively
transforms without attacks, meaning symptoms increase in severity.
C) Primary Progressive MS (PPMS); steady increase in severity without attacks.
Prognosis
Improving or progressive (depends on the “attack” episodes and brain MRI lesions)
Respiratory Significance
Muscle weakness can occur in the ventilatory muscles of the chest and abdomen that are
involved in breathing and often develops overtime leading to RF. Also, presence of lesions
within or affecting respiratory centers of the brain could lead to respiratory consequences.
* Case recall: patient’s MRI reflects lesions in pons, she might have undocumented episodes of dyspnea
C) Diagnostics:
Note: There is no single diagnostic test for MS

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ANTONIO, DESIERY K. BSRT 2 May 10, 2020

Magnetic Resonance Imaging (MRI): presence of white matter plaques (see arrows below)

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ANTONIO, DESIERY K. BSRT 2 May 10, 2020

Cerebrospinal Fluid (CSF) examination: increase of mononuclear

(e.g. lymphocytes, monocytes) cell count and synthesis of IgG (an
antibody) in the CSF. Total CSF protein is usually normal or mildly
elevated
 Evoked Potentials: measure response to visual, auditory or
somatosensory stimuli
*Case recall: patient had left eye acuity of 10/100, elevated lymphocytes and lesions on MRI scan

D) Treatment
 Rx of acute attacks
Corticosteroids/Glucocorticoid (IV or oral); provide short-term clinical benefit by reducing the
severity and shortening the duration of attacks. It works by reducing the swelling and
inflammation in the plaques during demyelination
 Long-term Rx
Interferon β & Glatiramer Acetate (subcutaneous); down regulates immune system, limits
inflammatory activity and inhibits T-cell proliferation which consequently reduces the attack rate.
Notalizumab; highly effective, It prevents lymphocytes from binding to endothelial cells, thereby
preventing lymphocytes from penetrating the BBB and entering the CNS
 Symptomatic Rx (treatment directed to the symptoms, some examples below)
Ataxia/tremor= Clonezepam Weakness= potassium channel blockers (e.g.,4-aminopyridine)
Spasms= regular exercise & stretching, baclofen, diazepam

Abbas,A.K., Aster, J.C., & Kumar, V. (2017). Robbins basic pathology. (10th ed). Canada: Elsevier.
Fauci, A., and Kasper, D., et al. (2018). Harrison’s principles of internal medicine. (20th ed). USA: McGraw Hill Education.
Klein, J.P. and Prasad, S., et al. (2019). Adams and Victor’s principles of neurology. (11th ed).USA: McGraw Hill Education.
Murray, T.J. (2017). Multiple Sclerosis; A guide for the newly diagnosed. (5th ed). USA: McNaughton & Gunn.

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