Case Presentation

Noah Marzook

11 year old

Recurrent visual lossSteroid therapy

Loss of central vision

Decrease visual acuity

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

Optic Neuropathies

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 loss2. Afferent pupillary defect3. Papilitis 4. Optic atrophy

Optic neuropathies▫ Optic neuritis

1. Demylinating2. Infectious3. 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

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

Optic neuritis

Optic Neuritis

•Sub category of optic neuropathies1. 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

2. Inflammatory1. Parainfectious

Post viral Post vaccination phenomenon

2. Sarcoidosis Bilateral Granulomatous infiltration

3. Autoimmune diseases SLE, sjogen’s, Bechets, IBD,

Granulomatosis with polyangiitis (GPA).

3. Inflammatory Demylinating ON

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.

Pathophsiology

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]

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

Why was this patient Diagnosed as MS?

•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

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

Multiple Sclerosis

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

Clinical features

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 MS Kriss 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.

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.

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.

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.

Acute disseminating Encephalomyelitis

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.

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

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.

Neuromylitis Optica

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

• 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

Which of the following Does our patient have?

MSADEM

NMOCIS

Why is it important?

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)

• 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.

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 

Thank You