oral presentation of my study

1. By
Shereen Fathi MD, Fatma Taha MD, Abdelazim Reda MD, Wael Ezzat
Presented by
Wael Mahmoud Ezzat
Assistant Lecturer of Neurology
Cairo University
2014

2. 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.
Wael Ezzat, 2014
UVR in MS

3. 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.
Wael Ezzat, 2014
UVR in MS

4. 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.
Wael Ezzat, 2014
UVR in MS

5. • 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
UVR in MS

6. 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.
Wael Ezzat, 2014
UVR in MS

7.  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.
Wael Ezzat, 2014
UVR in MS

8. 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).
Wael Ezzat, 2014
UVR in MS

9. 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.
Wael Ezzat, 2014
UVR in MS

10. 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.
Wael Ezzat, 2014
UVR in MS

11. Brief Ataxia Rating Scale (BARS)
 BARS is valid, reliable, and sufficiently fast and accurate for clinical
purposes. It measures ataxia among our patients.
Wael Ezzat, 2014
UVR in MS

12. 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
Wael Ezzat, 2014
UVR in MS

13. 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

14. 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.
UVR in MS

15. Wael Ezzat, 2014
• 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

16. 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.
Wael Ezzat, 2014
UVR in MS

17. 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).
Wael Ezzat, 2014
UVR in MS

18. 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).
Wael Ezzat, 2014
UVR in MS

19. 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).
Wael Ezzat, 2014
UVR in MS

20. 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
Wael Ezzat, 2014
UVR in MS

21. 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
Wael Ezzat, 2014
UVR in MS

22. 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
Wael Ezzat, 2014
UVR in MS

23. 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.
Wael Ezzat, 2014
UVR in MS

24. 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.
Wael Ezzat, 2014
UVR in MS

25. 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*
Wael Ezzat, 2014
UVR in MS

26. 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.
Wael Ezzat, 2014
UVR in MS

27. 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.Wael Ezzat, 2014
UVR in MS

28. Wael Ezzat, 2014
 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

29. Thank you
Wael Ezzat, 2014
UVR in MS