This case presentation is for Noah Marzook, who presented with decreased vision in both eyes, more severe in the right eye, along with a central visual field defect in the right eye. MRI showed bilateral optic nerve swelling and white matter lesions. Given the clinical features of optic neuritis and MRI findings, the patient was diagnosed with multiple sclerosis (MS). MS is characterized by episodes of demyelination in the central nervous system. A history of optic neuritis significantly increases the risk of developing MS within 10-15 years. Early treatment of MS can delay progression to clinically definite MS but long-term effects on disability are unknown.

1. Case Presentation
Noah Marzook

3. Eye examination
• No inflamation, Swelling, Poptosis, Skin
defects
• Normal extraocular movements, no
nystagmus, normal occular allighnment
• Decrease in visual acuaty of both eyes,
more at right eye.
• Visual field loss of central part of right
eye (Central scotoma).
• Normal red reflex
• Normal optic disc with no swelling, no
cupping, or loss of borders, normal
macula

4. Optic Neuropathies

5. Optic Neuropathies
• Diseases effecting the Optic nerve
• The optic nerve is considered part of the CNS
▫ Mylin sheeth from oligodenrocutes
▫ Covered in mengies
• Damage would lead to
1. Visual loss
2. Afferent pupillary defect
3. Papilitis
4. Optic atrophy

6. Optic neuropathies
▫ Optic neuritis
1. Demylinating
2. Infectious
3. Inflammatory
▫ Para infectious
▫ Systemic auto immune disease
▫ Infiltrative
▫ Compressive (Abscess, neoplasm, aneurysm)
▫ Ischemic (old age)
▫ Trauma
▫ Increase intracranial pressure (psudotumer cerebri)
▫ Drugs and toxins (ethambutol)
▫ Genitic
 Leber’s herediary optic neuropathy
 Kjer’s dissease
▫ Nutritional deficencies (Vitamin B12, B1, Folate)
▫ Radiastion in past 6 -12 months

7. MRI
• Bilateral Optic nerve swelling
• Lesions in the partial and temporal lobes
• No mass effect, No enhancements
• No edema or midline shift
• Impression: Multiple white matter lesions,
suggesting white matter plaques

8. Optic neuritis

9. Optic Neuritis
• Sub category of optic neuropathies
1. Infectious
▫ Isolated infection of the eye
 Acute viral infections
 Cat scratch disease
 Toxoplasmosis
▫ Mengitis and encphilitis may cause optic nuritis
either by dirct effect or secondary vasculitis

10. 2. Inflammatory
1. Parainfectious
 Post viral
 Post vaccination phenomenon
2. Sarcoidosis
 Bilateral
 Granulomatous infiltration
3. Autoimmune diseases
 SLE, sjogen’s, Bechets, IBD, Granulomatosis with
polyangiitis (GPA).

11. 3. Inflammatory Demylinating ON

12. Epidemology
• Most cases occur in woman
• The incidence of O.N is highest in
populations located in higher altitudes
• In the U.S studies have estimated the annual
incidence of O.N as high as 6.4/1000
Beck RW, Trobe JD, Moke PS, et al. High- and low-risk profiles for the development of
multiple sclerosis within 10 years after optic neuritis: experience of the optic neuritis
treatment trial. Arch Ophthalmol 2003; 121:944.

13. Pathophsiology

14. Clinical presentation
• Optic neuritis clinical trial
• Most common clinical features:
▫ Vision loss 90%
▫ Eye pain 92%
▫ Afferent pupillary defect 100% if unilateral
▫ Visual field defect (central scotoma)
▫ Photospiasas
▫ Loss of color vision
• Without treatment vision usually improves in 2-
4 weeks Optic Neuritis Study Group Coordinating Center, Jaeb Center for Health Research,
Tampa, FL 33647, USA. ontt@jaeb.org, . Archives of Ophthalmology [2003,
121(7):944-949]

15. Investigations
• MRI
▫ 95% would show inflammation of the optic nerve
▫ Lesions may be visualized in the brain white
matter
• LP
▫ Mylien basic protien, IgG synthesis, Oligoclonal
bands
• Delay in visual evoked potential

16. Why was this patient Diagnosed as MS?

17. • Clinical isolated syndrome
▫ Acute first episode
▫ Presumed inflammatory demylinating etiology
▫ No previous history of central dymylinating event
• OR It could be part of a more diffuse
dymylinating disease

18. Demylinating Diseases in The CNS
• Optic neuritis
• Transverse Mylitis
• Multiple sclerosis
• Acute deseminated encepthelo mylitis
• Neuromylitis optica
• No disesease specific biomarkers execpt in NMO.
• Difficult to distinguish at initial presenatation
• Correct diagnosis requires
▫ Clinical features
▫ Laboratory results
▫ Imagining findings

19. Multiple Sclerosis

20. MS
• Multiple sclerosis (MS) is characterized by
recurrent episodes of demyelination in the
central nervous system (CNS) separated in space
and time.
• Acute inflammation and demyelination in a
critical area of the brain, optic nerves, or spinal
cord will produce a corresponding clinical deficit

21. Clinical features

22. Prevalence
• Age <18 = 5% of
patients with MS
• Age < 10 = 1%
• Girl/Boy ratio is 2.8 .
• 1.35 to 2.5 per
100,000 children. In
the United States, it
is estimated that
there are 8000 to
10,000 children with
MSKriss A, Francis DA, Cuendet F, et al. Recovery after optic neuritis in childhood. J Neurol Neurosurg Psychiatry 1988;
51:1253.
KENNEDY C, CARROLL FD. Optic neuritis in children. Arch Ophthalmol 1960; 63:747.
Lucchinetti CF, Kiers L, O'Duffy A, et al. Risk factors for developing multiple sclerosis after childhood optic neuritis.
Neurology 1997; 49:1413.

23. MS Saudi Arabia
• 1998;39(3):182-6.Pattern of presentation of multiple sclerosis in
Saudi Arabia: analysis based on clinical and paraclinical
features.Daif AK, Al-Rajeh S, Awada A, Al Bunyan M, Ogunniyi A,
AbdulJabar M, Al Tahan AR.Department of Medicine, King Khalid
University Hospital, King Saud University, Riyadh, Saudi Arabia.
▫ 89 MS patients comprising 38 males and 51 females seen over a 10-year period
▫ The mean age at onset of Saudi patients (25.9 years) was lower than that of the
non-Saudis (29.4 years; p < 0.001).
▫ Involvement of the pyramidal system was the commonest mode of presentation.
▫ The clinical course was relapsing-remitting in 60.7%, progressive-relapsing in
20.2% and primary progressive in 19.1%.
▫ The number of systems involved was significantly associated with the duration of
disease (p < 0.001). The demographic features and the variability of clinical
presentation of Saudi MS patients is similar to the results from neighbouring
countries.

24. Epidemiology
• Genetic susceptibility
▫ First-degree relatives 5%
▫ Monozygotic twins 25%
• Certain immunologic human leukocyte antigen
(HLA) genes (HLA DRB1*1501, DQA1*0102, and DQB1*0602)
• Environmental triggers
Beck RW, Trobe JD, Moke PS, et al. High- and low-risk profiles for the development of multiple sclerosis within 10 years
after optic neuritis: experience of the optic neuritis treatment trial. Arch Ophthalmol 2003; 121:944.

27. Time and Space
• Dissemination in space
▫ MRI Lesions in THE periventricular,
juxtacortical, infratentorial, or spinal cord. At least
two, in two different locations
▫ Clinical different neurologic deficit
• Dissemination in time
▫ MRI Simultaneous presence of lesions at any time
or a new lesion(s) on follow-up MRI
▫ Clinical by the development of a second clinical
attack.

29. Acute disseminating Encephalomyelitis

30. ADEM
• Also known a post infectious encephelomylitis
• Acute or subacute onset, of multi focal defect and
encephelopathy
• Rare disease
▫ 0.2/100,000 per year in Canada.
▫ 0.4/ 100,000 in USA
• Preceded by a viral or bacterial infection
▫ In three series, an antecedent infection could be
identified in 72 to 77 percent of patients
• Most cases in winter and spring
• Present one month of their illness
Leake JA, Albani S, Kao AS, et al. Acute disseminated encephalomyelitis in childhood:
epidemiologic, clinical and laboratory features. Pediatr Infect Dis J 2004; 23:756.

31. Clinical features
• Fever, headache, vomiting and menigisum
• Encephalopathy, ranging from lethargy to
coma
• Febrile illness 50-75% in the past 4 weeks
• Neurologic symptoms 4 – 13 days after
• Seizure in 1/3 of patients
• Typical last 2-4 weeks

32. Post Vaccination
• Less than 5% of ADEM cases follow
immunization.
• Association with Hib, influenza, Japanese B
encephalitis, DTP, measles, mumps..
• Incidence of ADEM associated with live measles
vaccination (1-2/million)
• Incidence post infection with measles (1/1,000)
Fenichel GM. Neurological complications of
immunization. Ann Neurol 1982; 12:119.

34. Neuromylitis Optica

35. NMO
• Classic neuromyelitis optica
▫ Bilateral optic neuropathy and transverse
myelitis.
▫ The optic neuritis and transverse myelitis can
occur concurrently, or one may follow the other.
• While NMO may be closely related to MS, the
disorders can be differentiated by application of
strict diagnostic criteria

37. • May have MRI lessions similar to those of ADEM
and MS
• Poorer prognosis.
• Myelopathy more severe. Less likely to recover.
• Serum IgG autoantibody
• Aretrospective study with clinical information
available for 58 children (4 to 18 years old) who
were seropositive for NMO-IgG and followed for a
median of 12 months, showed:
• Attacks of optic neuritis, transverse myelitis, or both
were noted in 98 percent

39. Which of the following Does our
patient have?

41. Why is it important?

42. Risk of developing MS
• In the ONTT, the risk of developing multiple sclerosis
• 5 years = 30%
• 12 years = 40%
• 15 years = 50%
• In 10 years in relation to MRI findings
▫ With MRI findings = 56 %
▫ No MRI findings = 22 %
• Oligoclonal bands
▫ A study of 415 patients with CIS, with oligoclonal bands was
associated with a significantly increased risk of developing
clinically definite multiple sclerosis (hazard ratio 1.7, 95%
CI 1.1-2.7)

43. • Figure
• Life-Table Analysis of MS According to Number of Baseline MRI Lesions
• Life-table intervals are defined by annual exams during the first five years, the periods between the 5 and 10 year exams, and between the
10 and 15 year exams. The table under the horizontal axis represents the number of patients in follow-up who had not developed MS at
the end of the previous interval. Patients with one and two MRI lesions were combined into one group because MS rates were similar.

44. Early Treatment
• Early treatment can delay conversion to clinically
definite multiple sclerosis.
• However, it is unknown whether such treatments
prevent or delay long-term disability.
• Interferons - Randomized controlled trials
(CHAMPS, ETOMS, and REFLEX) 1160 patients (639 treatment
and 521 placebo) . (pooled odds ratio [OR] 0.53, 95% CI 0.40-0.71) and at two years of
follow-up (pooled OR 0.52, 95% CI 0.38-0.70).
• Glatiramer acetate - PreCISe trial The trial was stopped early
because of benefit with a mean average exposure to glatiramer of 2.3 years. By
intention-to-treat analysis, glatiramer acetate (20 mg subcutaneously daily) therapy
significantly reduced the risk of conversion to clinically definite multiple sclerosis
(hazard ratio 0.55, 95% CI 0.40-0.77),
• Intravenous immune globulin