By

Shereen Fathi MD, Fatma Taha MD, Abdelazim Reda MD, Wael Ezzat

Presented by

Wael Mahmoud Ezzat

Assistant Lecturer of Neurology

Cairo University

2014

Aim of The Work

To detect the impact of use of UVR therapy on Relapsing Remitting Multiple Sclerosis (RRMS) patients through clinical, laboratory, radiologically and with neurophysiological assessment.

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Pathophysiology & Etiology of

Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) resulting in accumulating neurological disability.

The etiology of MS is unknown. It is regarded as a complex

Multi-causal disease. The etiological factors comprise:

a) Genetic factors.

b) Dysfunction of the immune system (autoimmunity).

c) Environmental factors.

• Environmental risk factors are strongly related to multiple sclerosis. The effects of latitude, climate and, most recently, hypo-vitaminosis D have successively been considered.

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Role of Vitamin D & UVR therapy

in Multiple Sclerosis

Vitamin D deficiency is common in patients with MS. A recent, large

epidemiological study showed that women with the highest vitamin D

intakes (used supplements) had a 40% reduction in the risk of developing

MS.

The cause of low vitamin D levels in MS patients is likely to be due to a

combination of low vitamin intakes and decreased outdoor activities in

climates that are not optimal for vitamin D synthesis in the skin.

Interest in vitamin D and MS originated from identification of a negative

correlation between exposure to sunlight and prevalence of MS.

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• Recent work suggests that UVR exposure may be one factor

that can attenuate Th1-mediated immune responses through

several mechanisms:

1. UVR can cause local immunosuppression .

2. the active form of vitamin D (1,25(OH)2D3), derived from

UVR-supported biosynthesis, has immunomodulatory effects.

• However, ingested vitamin D does not completely reproduce

the effects of UVR exposure: UVR stimulates neuroendocrine

and immune modulating pathways that may function

independently of vitamin D production or that may act in

concert with vitamin D produced in the skin. Wael Ezzat, 2014

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Patients

Patients were selected consecutively from neurology

outpatient clinic and Neurology department in Kasr Alainy

Hospital from January 2013 till February 2014. This case

control study included 40 patients with clinically definite

relapsing remitting multiple sclerosis according to the

McDonald diagnostic criteria for multiple sclerosis revised

2011.

Patients were classified into two groups:

Group I (study group): included 20 patients with RRMS received

methylprednisolone and UVR therapy sessions during their

remission period.

Group II (control): included 20 patients with RRMS received

methylprednisolone only.

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Inclusion Criteria:

1. Relapsing Remitting Multiple

Sclerosis (RRMS) patients

during their remission period.

2. Age: from 20 to 50ys.

Exclusion Criteria:

1. Patients taking vitamin D.

2. Patients on immunosuppressives

or interferone.

3. Patients with photosensitivity.

4. Patients with SLE or vasculitis.

5. Patients exposed to radiation.

6. Pregnant patients.

7. patients not completed his UVR therapy sessions.

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Methods

All patients in this study were submitted to the following:

1. Thorough history taking.

2. Thorough general medical examination.

3. Thorough neurological examination according to the standardized neurological sheet.

4. Clinical rating scales: • Expanded Disability Status Scale (EDSS). • Modified Ashworth Scale for grading Spasticity (MAS). • Brief ataxia rating scale (BARS). • The International Prostate Symptom Score (I-PSS).

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Expanded Disability Status Scale (EDSS)

The Kurtzke Disability Status Scale (DSS) was developed by Dr. John

Kurtzke in the 1950s to measure the disability status of people with multiple sclerosis.

The EDSS quantifies disability in eight Functional Systems (FS):

a) -Pyramidal functions.

b) -Cerebellar functions.

c) -Brainstem functions.

d) -Sensory functions.

e) -Bowel and bladder functions.

f) -Visual functions.

g) -Mental functions.

h) -Other function.

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Modified Ashworth Scale for grading Spasticity (MAS)

Ashworth's scale assigns grades to a manually determined resistance of

muscle to passive stretching, it measures spasticity as defined herein.

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Brief Ataxia Rating Scale (BARS)

BARS is valid, reliable, and sufficiently fast and accurate for clinical

purposes. It measures ataxia among our patients.

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The International Prostate Symptom Score (I-PSS)

The International Prostate Symptom Score (I-PSS) is based on the answers

to seven questions concerning urinary symptoms and one question

concerning quality of life.

The questions refer to the following urinary symptoms:

Questions Symptom

1 Incomplete emptying

2 Frequency

3 Intermittency

4 Urgency

5 Weak Stream

6 Straining

7 Nocturia

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Wael Ezzat, 2014

5. Neurophysiology:

• Visual evoked potential (VEP).

• H-reflex.

6. Neuro-imaging:

• MRI brain & spinal cord with contrast.

7. Laboratory:

• Routine laboratory tests.

• Serum Vitamin D level: Assay of serum 25-hydroxy-cholecalciferol 25 )OH ( D by

ELISA technique. Samples are collected pre testing in both groups I & II, and after 1

month & after 3 months post testing in group I only.

UVR in MS

Wael Ezzat, 2014

8. Ultra-Violet Radiation Therapy (for group I only):

• The objective of Vitamin D phototherapy is to use the UVB light generated by

the device to create the natural biological reaction in the skin that results in the

formation of Vitamin D.

• The amount of Vitamin D produced in the body is directly related to the number

of UVB photons (light particles) that penetrate the skin to the biologically

active skin layers.

• Studies have shown that a single dose of whole-body sub-erythemal UVB can

create the equivalent of 10,000 to 20,000 IU of oral Vitamin D. However, this

is the maximum dose that ever ought to be taken as it exposes the patient to

greater risk of burning. It is instead likely safer to take more frequent smaller

doses.

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• Group I (20 patients) will receive methylprednisolone for MS, in addition to

broad band UVB (280 - 315 nm) radiation on the whole back and neck regions

from 50 cm distance perpendicularly for 10 minutes, once every other day for

12 sessions (4 weeks).

UVR in MS

Results

Demographic data:

1.Age:

The age of the patients in this study ranged from 20 - 48 years.

No statistically significant difference was detected between group I and II as regarding the age

of the patients.

2. Sex:

• The prevalence of multiple sclerosis in Egypt was found to be 1.41% or 14.1 in 1000 neurological patients, the female to male ratio was 1.6:1

In our study, female patients (n=21) represented a relatively larger proportion (52.5%) in this

study compared to the male patients (n=19) (47.5%) and female to male ratio was 1.1:1. No

statistically significant difference was found between group I and II as regards the sex

distribution.

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Clinically:

A statistically significant difference was detected between pre and post UVR therapy

patients regarding sensory system, 60% of cases in group I was affected pre UVR and

50% improved on UVR therapy leaving only 10% of cases affected (P=0.021), regarding

sphincteric manifestations, 60% of cases in group I was affected pre UVR and 20%

improved on UVR therapy leaving 40% of cases affected (P=0.005).

A Statistically significant difference on a testing the cranial nerves involvement among

our group I & II patients, we found that there is marked improvement in cranial nerves in

group I (post) and this was Statistically significant (P=0.002).

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Results of Clinical scales:

A statistically significant difference was detected between pre and post UVR therapy

patients regarding EDSS (P=0.01), I-PSS (P=0.02), BARS (P=0.02) being lower in group

I (post).

A statistically significant difference was detected between group II and group I post UVR

therapy patients regarding BARS being lower in post (P=0.04).

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Neurophysiology:

A statistically significant difference was detected between pre and post UVR therapy

patients regarding VEP latency in Rt side (P=0.01) and H-reflex latency in UL (P=0.001) &

in LL (P=0.001) being delayed in pre exposure.

A statistically significant difference was detected between group II and group I post UVR

therapy patients regarding H-reflex latency in UL being delayed in post UVR therapy

(P=0.0180).

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MRI brain and spinal cord with contrast:

Although, No statistically significant difference was detected between pre and

post UVR therapy patients, the number of lesions post UVR therapy was lower

compared to group II.

Range(num

ber of

lesions)

mean SD P-value

Group

II

3-11 6.45 2.28 0.57

Group

I (post)

3-9 6.10 1.58

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New Attacks:

The number of new attacks post UVR therapy (4 patients=20% developed a total

of 5 new attacks) was lower than in group II patients (7 patients=35% developed a

total of 8 new attacks) but, No statistically significant difference was detected

between group II and group I (post) UVR therapy patients regarding number of

new attacks.

Range(n

umber

of

attacks)

Mean SD P-value

Group II 0-2 0.35 0.58 0.39

Group

I(post)

0-2 0.20 0.52

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Serum Vitamin D (25-hydroxy-cholecalcifirol) level:

The serum 25 hydroxy-cholecalcifirol in this study ranged from 21.5 ng/ml -

77 ng/ml.

Mean SD P-value

Vit D level Group II 34.11 5.18 0.004*

Group

I(pre)

31.05 7.45

Group II 34.11 5.18 0.86

Group I

(Post 1m)

34.66 5.86

Group II 34.11 5.18 0.026*

Group I

(Post 3m)

37.87 9.81

Group I

(pre)

31.05 7.45 <0.001*

Group I

(Post 1m)

34.66 5.86

Group I

(Post 3m)

37.87 9.81

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A statistically significant rise was detected in serum 25 hydroxy-

cholecalcifirol level between pre and post 1-month and post 3-months

(P=<0.001, P=0.004, P=0.003 respectively) UVR therapy patients.

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Serum Vitamin D level according to sex:

No statistically significant difference was detected in serum 25 hydroxy-

cholecalcifirol pre, post 1m & post 3m UVR therapy between males and

females patients.

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Correlations of means serum Vitamin D level Diff-D1 (difference between pre &

post1m) and Diff-D2 (difference between pre & post 3m) among our groups

A statistically significant difference was detected in serum 25 hydroxy-cholecalcifirol

between Diff-D1 and Diff-D2 (p=<0.001) being higher in Diff-D2.

Mean SD Min. Max.

Diff-D1 3.60 5.06 -5 18

Diff-D2 6.81 11.59 -15 49

Correlation

Coefficient

Significance(sig)

Diff-D1

Diff-D2

0.92 <0.001*

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Conclusion

A statistically significant decrease in EDSS, I-PSS and BARS scores, with a

parallel statistically significant improvement in VEP latency and H-reflex

latency post UVR therapy was found.

Moreover, A statistically significant increase in serum Vitamin D (25-hydroxy-cholecalcifirol) level following UVR therapy was depicted.

Also, we noticed that the number of new attacks and number of MRI

lesions post UVR therapy was decreased, although not statistically

significant.

The role of UVR therapy in the pathogenesis of RRMS - via modulation in

Vitamin D status - has a peculiar impact on disease improvement and

control.

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Recommendations

In the light of this study, the following is recommended:

1.More extended study with longer period of follow-up to detect

change in MS relapse rate post UVR therapy.

2.Further studies, including longitudinal evaluation of vitamin D is

necessary to fully investigate the possible association between vitamin

D status and relapse rate in MS.

3. Further studies, to show immunological (non-vit D) effect of UVR

therapy on MS patients.

4. Vitamin D supplementation and UVR therapy for MS patients is

beneficial in improving their clinical state.

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A hidden scope has to be uncovered that is Receptor

hypersensetivity to vitamin D, that may play a significant role in

MS/vitamin D Mutual Relationship. Cave that needs navigation

and incrusion via PCR Analysis and radionuclide imaging. As

even though vitamin D level may be within normal levels , a

response to vitamin D may be unsatisfactory.

UVR in MS

Thank you

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