ArticlePDF Available

Multiple Sclerosis Presenting with Sixth Nerve Palsy in a Child

International Medical Case Reports Journal

August 2021
14:545-550

DOI:10.2147/IMCRJ.S320678

License
CC BY-NC 3.0

Authors:

We report a child with multiple sclerosis who presented with sixth nerve palsy. She is a twelve-year-old Bahraini female presented to the ophthalmology department complaining of double vision. She also had imbalance and paraesthesia. Extraocular muscle examination showed restriction of abduction in the right eye. There was no change in vision. MRI showed right eye optic neuritis (ON) and demyelination which was indicative of multiple sclerosis (MS). Ocular coherence tomography (OCT) showed thinning of nerve fibres of both eyes which was consistent with subclinical optic neuritis. Neurological examination showed brisk knee jerk on the left side and incoordination of movement on the same side. Disability Status Scale (EDSS) showed a score of 3.0. She was given Solu-medrol 500 mg intravenously (IV) in addition to omeprazole 40 mg IV and Vitamin D3 (cholecalciferol) 50,000 IU cap weekly for 8 weeks and Neurorubine forte tablets (vitamin B1, 6, 12) once a day for 2 months. She became asymptomatic in her follow-up visits. Children with MS can present as sixth cranial nerve palsy. Clinicians should have a high index of suspicion for early diagnosis and treatment. In addition to MRI, OCT is a useful diagnostic tool for optic neuritis and MS especially in children.

The patient’s extraocular eye movements in different gaze positions. (A) The patient is looking straight showing no limitation of extraocular muscles. (B) The patient is looking to the left. There is no limitation of extraocular muscle movements. (C) The patient is looking to the right. There is limitation of abduction of the right eye indicating weakness of the right lateral rectus muscle due to sixth nerve palsy.

…

Average RNFL thickness is asymmetrical in both eyes with 58% of asymmetry. RNFL thickness values for different locations of the optic nerve scans showing the average thickness in μm in superior, temporal, inferior and nasal quadrants. The RNFL in the nasal quadrant of the right eye and left eye are 68 μm and 59 μm, respectively. Both readings are significantly thin compared with normal controls (96 μm). The RNFL in the temporal quadrant of the left eye is 55 μm which is severely thin compared with normal controls (73 μm). This thinning of RNFL quadrants is consistent with ON.

…

MRI of brain. (A) T2 fat sat image right optic nerve hyperintensity indicating optic neuritis. (B) T2 axial image showing left cerebral peduncle plaque. (C) T2 axial showing right optic neuritis. (D) T1 axial post-contrast image showing patchy enhancement of right optic nerve. (E) Periventricular T2 hyperintense focus in right peritrigonal region. (F) Flair sagittal image showing ependymal dot-dash sign sensitive in early MS. (G) Diffusion-weighted image showing left peri ventricular bright focus- T2 shine through effect. (H) Flair axial image showing right parietal juxtacortical and left periventricular foci. (I) Flair axial image showing left parafalcine frontal juxtacortical focus. (J) Sagittal flair image showing juxtacortical and infratentorial plaques. (K) Diffusion-weighted image showing bright right optic nerve. (L–N) Open ring enhancement of juxtacortical plaque. (O) Nodular enhancement in periventricular plaque.

…

Figures - available from: International Medical Case Reports Journal

This content is subject to copyright. Terms and conditions apply.

Access to this full-text is provided by Taylor & Francis.

Learn more

Content available from International Medical Case Reports Journal

This content is subject to copyright. Terms and conditions apply.

CASE REPORT

Multiple Sclerosis Presenting with Sixth Nerve

Palsy in a Child

Nada Al-Yousuf

Lolwah Aljutaili

Aisha AlHuwais

Abdullah Almutairi

Hasan Alsetri

Moiz Bakhiet

Department of Ophthalmology, King

Abdullah Medical City, Manama, Kingdom

of Bahrain;

College of Medicine &

Medical Sciences, Arabian Gulf University,

Manama, Kingdom of Bahrain;

Department of Chemistry &

Biochemistry, University of California Los

Angeles, Los Angeles, CA, USA;

Department of Molecular Medicine,

College of Medicine & Medical Sciences,

Arabian Gulf University, Manama,

Kingdom of Bahrain

Abstract: We report a child with multiple sclerosis who presented with sixth nerve palsy.

She is a twelve-year-old Bahraini female presented to the ophthalmology department com-

plaining of double vision. She also had imbalance and paraesthesia. Extraocular muscle

examination showed restriction of abduction in the right eye. There was no change in vision.

MRI showed right eye optic neuritis (ON) and demyelination which was indicative of

multiple sclerosis (MS). Ocular coherence tomography (OCT) showed thinning of nerve

bres of both eyes which was consistent with subclinical optic neuritis. Neurological

examination showed brisk knee jerk on the left side and incoordination of movement on

the same side. Disability Status Scale (EDSS) showed a score of 3.0. She was given Solu-

medrol 500 mg intravenously (IV) in addition to omeprazole 40 mg IV and Vitamin D3

(cholecalciferol) 50,000 IU cap weekly for 8 weeks and Neurorubine forte tablets (vitamin

B1, 6, 12) once a day for 2 months. She became asymptomatic in her follow-up visits.

Children with MS can present as sixth cranial nerve palsy. Clinicians should have a high

index of suspicion for early diagnosis and treatment. In addition to MRI, OCT is a useful

diagnostic tool for optic neuritis and MS especially in children.

Keywords: demyelination, ocular coherence tomography, lateral rectus palsy, diplopia

Introduction

Multiple sclerosis (MS) was rst described in 1868 by French neurologist Jean-

Martin Charcot.

MS is considered as the most common immune disorder affecting

the central nervous system.

It affects around 2.3 million people globally.

Although it is more commonly seen farther from the equator, some ethnic groups,

staying far from the equator, have low prevalence.

4–6

Indeed, some ethnic groups

staying close to the equator were shown to have a relatively high risk of this

disease.

7,8

Data from the Middle East shows that the prevalence of MS is around

51.52/100,000, ranging from 14.77/100,000 in Kuwait to 101.4/100,000 in Turkey.

The incidence of MS in children and in patients below the age of 16 is reported

to be 2.7–5% of the total cases.

Clinical presentations of MS in children include

optic neuritis (ON), gait disorders, sensory and motor decits and brainstem

disturbances.

11,12

Compared to adults, it was reported that children were more

likely to have ocular symptoms.

13,14

Extraocular muscle weakness is not commonly reported in MS. Sixth nerve

palsy is a rare presentation of adult MS.

14–16

Children reported with sixth nerve

palsy is mostly due to neoplasms or trauma.

We report herewith a child with MS who presented with sixth nerve palsy,

subclinical optic neuritis and neurological symptoms. To the best of our knowledge,

Correspondence: Nada Al-Yousuf

Department of Ophthalmology, King

Abdullah Medical City, 61, King Abdulaziz

Avenue, Manama, Bahrain

Tel +973 77310071

Fax +973 77310001

Email nyousuf10@gmail.com

International Medical Case Reports Journal 2021:14 545–550 545

php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the

work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For

permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).

International Medical Case Reports Journal Dovepress

open access to scientiﬁc and medical research

Open Access Full Text Article

Received: 22 May 2021

Accepted: 30 July 2021

Published: 13 August 2021

this is the rst case of pediatric multiple sclerosis present-

ing as sixth nerve palsy to be reported from the Middle

East region. Written informed consent was provided by the

patient’s father to have the case details and photographs

published. Approval was required and was obtained from

the research committee of Habib Medical Group, the

administrative body that is managing the clinical aspect

of King Abdullah Medical City, to publish this case report.

Case Report

The patient is a twelve-year-old Bahraini female presented

to the ophthalmology department complaining of double

vision since one week. The diplopia was mainly on looking

straight and on right gaze. She had no prior viral illness.

She was fully vaccinated. She has an error of refraction and

uses glasses. Ophthalmic examination showed the follow-

ing: Visual acuity unaided was 0.7 in the right eye and 0.7

in the left eye. There was no relative afferent pupillary

defect (RAPD). Slit lamp ophthalmic examination showed

clear corneas, normal anterior chamber, normal lens and

iris pattern. Fundus examination showed normal maculae

and no swelling of the optic discs of both eyes. Extraocular

muscle examination showed restriction of abduction in the

right eye. The other eye movements were full (Figure 1).

Convergence was poor. Orthoptic examination was per-

formed. Worth’s Fourth Dot test showed suppression of

the right eye. Stereopsis test using random-dot stereogram

was 800 seconds of arc only. Titmus stereotest was also

abnormal. Krimsky test showed a deviation angle of 20

prism dioptre of esotropia in the right eye for near and

distance vision. Performing subjective refraction , the right

eye, with −0.75 cylinder correction at 10 degrees, her

vision was 0.8. Performing subjective refraction, the left

eye, with −0.75 spherical correction, her vision was 0.8.

Ocular coherence tomography (OCT) was done. It showed

thinning of the retinal nerve bre layer (RNFL) of both

eyes. The average RNFL thickness is asymmetrical in both

eyes with 58% of asymmetry. The RNFL in the nasal

quadrant of the right eye and left eye are 68 μm and 59

μm, respectively. The RNFL in the temporal quadrant of

the left eye is 55 μm (Figure 2). MRI of brain was done.

Pre- and post-intravenous contrast multiplanar and multi-

sequential MRI study of the brain was performed. Multiple

periventricular and deep white matter nodular small foci

Figure 1 The patient’s extraocular eye movements in different gaze positions. (A) The patient is looking straight showing no limitation of extraocular muscles. (B) The

patient is looking to the left. There is no limitation of extraocular muscle movements. (C) The patient is looking to the right. There is limitation of abduction of the right eye

indicating weakness of the right lateral rectus muscle due to sixth nerve palsy.

https://doi.org/10.2147/IMCRJ.S320678

DovePress

International Medical Case Reports Journal 2021:14

546

Al-Yousuf et al Dovepress

Figure 2 Average RNFL thickness is asymmetrical in both eyes with 58% of asymmetry. RNFL thickness values for different locations of the optic nerve scans showing the

average thickness in μm in superior, temporal, inferior and nasal quadrants. The RNFL in the nasal quadrant of the right eye and left eye are 68 μm and 59 μm, respectively.

Both readings are signicantly thin compared with normal controls (96 μm). The RNFL in the temporal quadrant of the left eye is 55 μm which is severely thin compared

with normal controls (73 μm). This thinning of RNFL quadrants is consistent with ON.

Abbreviations: OD, right eye; OS, left eye; RNFL, retinal nerve bre layer; ON, optic neuritis; S, superior; T, temporal; I, inferior; N, nasal.

International Medical Case Reports Journal 2021:14 https://doi.org/10.2147/IMCRJ.S320678

DovePress

547

Dovepress Al-Yousuf et al

are seen in both cerebral hemispheres including temporal

lobes. Nodular foci were seen at left frontal high periven-

tricular, left peritrigonal and posterosuperior to right Sylvia

ssure, left anteromedial margin of midbrain, and left

superior cerebellar peduncle. There was no intra- or extra-

axial collection of degraded blood products. Size and shape

of ventricles, basal cistern and cortical sulci were normal;

no midline shift; no posterior fossa masses; no cerebello-

pontine angle masses.; and normal cranio-cervical junction.

The MRI features were suggestive of demyelinating dis-

ease and optic neuritis (Figure 3). The impression was

multiple sclerosis with sixth nerve palsy and optic neuritis.

The patient was referred to neurology.

She had neurological symptoms, in addition to diplo-

pia, she had imbalance and paraesthesia. She had no fever,

headache or vomiting. There was no altered level of con-

sciousness, behavioral changes, acute cognitive dysfunc-

tion, and no seizures. There were no signs of decreased

voluntary movement, muscle weakness or incoordination

of movement. Disability was evaluated using the Kurtzke

Expanded Disability Status Scale (EDSS), and she had

a score of 3.0 with mild disability in three functional

systems (FS). Blood test for NMO antibodies was nega-

tive. Erythrocyte sedimentation rate (ESR) and C-reactive

protein (CRP) were within normal levels.

The diagnosis of MS was made. The patient was given

Solu-medrol 500 mg intravenously (IV), in addition to

omeprazole 40 mg IV and Vitamin D3 (cholecalciferol)

50,000 IU cap weekly for 8 weeks. Neurorubine forte

tablets (vitamin B1, 6, 12) were prescribed once a day

for 2 months. The patient received a tapering dose of

prednisolone 30 mg for 3 days and then reduced by

5 mg every 3 days with 20 mg of Nexium tablets daily.

One week later, the patient was reassessed and her EDSS

went down to 1.0 with no disability and minimal signs in

one FS. Patient was put on interferon-beta treatment as

a disease-modifying drug (DMD) and regularly followed

Figure 3 MRI of brain. (A) T2 fat sat image right optic nerve hyperintensity indicating optic neuritis. (B) T2 axial image showing left cerebral peduncle plaque. (C) T2 axial

showing right optic neuritis. (D) T1 axial post-contrast image showing patchy enhancement of right optic nerve. (E) Periventricular T2 hyperintense focus in right

peritrigonal region. (F) Flair sagittal image showing ependymal dot-dash sign sensitive in early MS. (G) Diffusion-weighted image showing left peri ventricular bright focus- T2

shine through effect. (H) Flair axial image showing right parietal juxtacortical and left periventricular foci. (I) Flair axial image showing left parafalcine frontal juxtacortical

focus. (J) Sagittal air image showing juxtacortical and infratentorial plaques. (K) Diffusion-weighted image showing bright right optic nerve. (L–N) Open ring enhancement

of juxtacortical plaque. (O) Nodular enhancement in periventricular plaque.

https://doi.org/10.2147/IMCRJ.S320678

DovePress

International Medical Case Reports Journal 2021:14

548

Al-Yousuf et al Dovepress

at the neurological clinic. Six months later, she was fully

recovered symptomatically.

Discussion

OCT is a useful tool in ON and MS which may reveal

thinning in the RNFL in the absence of clinical ndings.

18,19

OCT is a non-contact scanning machine that provides

cross-sectional visualization of the optic nerve head and

measurements of retinal nerve ber layer (RNFL) thick-

ness in different quadrants of the optic nerve. It has the

advantage of being noninvasive and can easily be per-

formed in pediatric age group. Unlike MRI, OCT does

not require sedation in children. It is particularly useful

in MS, in which the anterior visual pathways are com-

monly affected. RNFL thickness values for different

locations of the optic nerve scans show the average

thickness in μm in superior, temporal, inferior and

nasal quadrants. The patient’s RNFL thicknesses in the

nasal quadrant of the right eye and left eye are 68 μm

and 59 μm, respectively. Both readings are signicantly

thin compared with normal controls (96 μm).

The

RNFL in the temporal quadrant of the left eye is 55

μm, which is severely thin compared with normal con-

trols (73 μm).

This thinning of RNFL quadrants is

consistent with ON.

Our patient had no RAPD and no OD swelling, yet her

OCT results showed thinning in RNFL in both eyes.

Interestingly, although the MRI ndings suggested right

eye optic neuritis, there was bilateral thinning of the RNFL

on OCT, more in the left eye. This nding sheds light on the

importance of performing both MRI and OCT when inves-

tigating children with MS. RNFL thinning can be evident in

the absence of clinical and MRI ndings.

It is not uncommon for children with MS to present

with ON. However, sixth nerve palsy, as a presenting sign

in pediatric MS, is rare.

21–23

A series of cases of pediatric MS were reported from

Taiwan, none of them presented as sixth nerve palsy.

Isolated sixth nerve palsy in children without MS was

reported in the medical literature.

25,26

Searching the literature

for pediatric MS with sixth nerve palsy, one case was reported

from Brazil, a child with MS who presented with diplopia and

convergent strabismus and found to have sixth nerve palsy.

Conclusion

Pediatric multiple sclerosis can present as sixth cranial

nerve palsy. Clinicians should have a high index of

suspicion for early diagnosis and treatment. In addition

to MRI, optic neuritis can be diagnosed by OCT, even in

the absence of clinical signs.

Future studies to investigate MRI and OCT correlation

in optic neuritis, especially in children, are recommended.

Acknowledgment

We thank Dr Jameel Ahmed, consultant radiologist at King

Abdullah Medical City, for providing us with additional

MRI sections with detailed explanations.

Disclosure

The authors report no conicts of interest in this work.

References

1. Charcot M. Histologie de la sclérose en plaques. Gaz Hosp.

1868;41:554–556.

2. Berer K, Krishnamoorthy G. Microbial view of central nervous

system autoimmunity. FEBS Lett. 2014;588(22):4207–4213.

doi:10.1016/j.febslet.2014.04.007

3. Disease GBD, Injury I, Prevalence C. Global, regional, and national

incidence, prevalence, and years lived with disability for 310 diseases

and injuries, 1990–2015: a systematic analysis for the Global Burden

of Disease Study 2015. Lancet. 2016;388(10053):1545–1602.

4. Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372

(9648):1502–1517. doi:10.1016/S0140-6736(08)61620-7

5. Alonso A, Hernan MA. Temporal trends in the incidence of multiple

sclerosis: a systematic review. Neurology. 2008;71(2):129–135.

doi:10.1212/01.wnl.0000316802.35974.34

6. Pugliatti M, Sotgiu S, Rosati G. The worldwide prevalence of multi-

ple sclerosis. Clin Neurol Neurosurg. 2002;104(3):182–191.

doi:10.1016/S0303-8467(02)00036-7

7. Milo R, Kahana E. Multiple sclerosis: geoepidemiology, genetics and

the environment. Autoimmun Rev. 2010;9(5):A387–394. doi:10.1016/

j.autrev.2009.11.010

8. Grimaldi LM, Salemi G, Grimaldi G, et al. High incidence and

increasing prevalence of MS in Enna (Sicily), Southern Italy.

Neurology. 2001;57(10):1891–1893. doi:10.1212/WNL.57.10.1891

9. Heydarpour P, Khoshkish S, Abtahi S, et al. Multiple sclerosis epi-

demiology in Middle East and North Africa: a systematic review and

meta-analysis. Neuroepidemiology. 2015;44(4):232–244. doi:10.115

9/000431042

10. Boiko A, Vorobeychik G, Paty D, et al. Early onset multiple sclerosis:

a longitudinal study. Neurology. 2002;59(7):1006–1010. doi:10.1212/

WNL.59.7.1006

11. Simone IL, Carrara D, Tortorella C, et al. Course and prognosis in

early-onset MS: comparison with adult-onset forms. Neurology.

2002;59(12):1922–1928. doi:10.1212/01.WNL.0000036907.37650.8E

12. Ozakbas S, Idiman E, Baklan B, et al. Childhood and juvenile onset

multiple sclerosis: clinical and paraclinical features. Brain Dev.

2003;25(4):233–236. doi:10.1016/S0387-7604(03)00034-2

13. Kaufmann DI. Multiple sclerosis and the eye. Ophthalmol Clin North

Am. 1992;5:513–531.

14. Thomke F, Lensch E, Ringel K, et al. Isolated cranial nerve palsies in

multiple sclerosis. J Neurol Neurosurg Psychiatry. 1997;63

(5):682–685. doi:10.1136/jnnp.63.5.682

15. Barr D, Kupersmith MJ, Turbin R, et al. Isolated sixth nerve palsy: an

uncommon presenting sign of multiple sclerosis. J Neurol. 2000;247

(9):701–704. doi:10.1007/s004150070114

International Medical Case Reports Journal 2021:14 https://doi.org/10.2147/IMCRJ.S320678

DovePress

549

Dovepress Al-Yousuf et al

16. Muhammed K, Ball J. Multiple sclerosis causing a partial sixth nerve

palsy. BMJ Case Rep. 2014;2014:bcr2013201239.

17. Park KA, Oh SY, Min JH, et al. Acquired onset of third, fourth, and

sixth cranial nerve palsies in children and adolescents. Eye (Lond).

2019;33(6):965–973. doi:10.1038/s41433-019-0353-y

18. Lamirel C, Newman NJ, Biousse V. Optical coherence tomography

(OCT) in optic neuritis and multiple sclerosis. Rev Neurol (Paris).

2010;166(12):978–986. doi:10.1016/j.neurol.2010.03.024

19. Graves JS, Chohan H, Cedars B, et al. Sex differences and subclinical

retinal injury in pediatric-onset MS. Mult Scler. 2017;23(3):447–455.

doi:10.1177/1352458516652497

20. Yanni SE, Wang J, Cheng CS, et al. Normative reference ranges for

the retinal nerve ber layer, macula, and retinal layer thicknesses in

children. Am J Ophthalmol. 2013;155(2):354–360 e351. doi:10.1016/

j.ajo.2012.08.010

21. Sivaraman I, Moodley M. Multiple sclerosis in the very young: a case

report and review of the literature. Neurodegener Dis Manag. 2016;6

(1):31–36. doi:10.2217/nmt.15.70

22. Suppiej A, Cainelli E. Cognitive dysfunction in pediatric multiple

sclerosis. Neuropsychiatr Dis Treat. 2014;10:1385–1392.

doi:10.2147/NDT.S48495

23. Domingo R, Martinez-Salcedo E, Climent V, et al. [Multiple sclero-

sis: a case report of early onset]. Rev Neurol. 1999;28(5):488–491.

Portuguese.

24. Weng WC, Yang CC, Yu TW, et al. Multiple sclerosis with childhood

onset: report of 21 cases in Taiwan. Pediatr Neurol. 2006;35

(5):327–334. doi:10.1016/j.pediatrneurol.2006.05.002

25. Gonçalves R, Coelho P, Menezes C, Ribeiro I. Benign recurrent sixth

nerve palsy in a child. Case Rep Ophthalmol Med.

2017;2017:8276256. doi:10.1155/2017/8276256

26. Mahoney NR, Liu GT. Benign recurrent sixth (abducens) nerve

palsies in children. Arch Dis Child. 2009;94(5):394–396. Epub

2009 Jan 8. PMID: 19131423. doi:10.1136/adc.2008.142794

27. de Albuquerque RC, de Paula RS, Brito MM, et al. Pediatric multiple

sclerosis – a challenging demyelinating disease: case report and brief

review of the literature. Case Rep Pediatr. 2012;2012:684064.

International Medical Case Reports Journal Dovepress

Publish your work in this journal

The International Medical Case Reports Journal is an international,

peer-reviewed open-access journal publishing original case reports

from all medical specialties. Previously unpublished medical posters

are also accepted relating to any area of clinical or preclinical

science. Submissions should not normally exceed 2,000 words or 4

published pages including gures, diagrams and references. The

manuscript management system is completely online and includes

a very quick and fair peer-review system, which is all easy to use.

Visit http://www.dovepress.com/testimonials.php to read real quotes

from published authors.

Submit your manuscript here: https://www.dovepress.com/international-medical-case-reports-journal-journal

DovePress International Medical Case Reports Journal 2021:14

550

Al-Yousuf et al Dovepress

Available via license: CC BY-NC 3.0

Content may be subject to copyright.

ResearchGate has not been able to resolve any citations for this publication.

Acquired onset of third, fourth, and sixth cranial nerve palsies in children and adolescents

Article

Full-text available

Feb 2019

To describe the causes of third, fourth, and sixth cranial nerve palsies in children and adolescents. In this retrospective case series, a total of 66 patients aged 0–19 years with third, fourth, and sixth cranial nerve palsies seen in strabismus and neuro-ophthalmic practice from 2010 to 2017 were included. Causes of palsies were determined based on clinical assessment, high-resolution magnetic resonance imaging (MRI), and laboratory work-up. Thirty-five patients had sixth cranial nerve palsy, 14 patients had third cranial nerve palsy (7 partial, 7 complete), 13 patients had fourth cranial nerve palsy, and 4 patients had combined cranial nerve palsies in this study. Neoplasia involving central nervous system was one of the most common causes of third, fourth, and sixth cranial nerve palsies both in children (age: 0–14 years) and adolescents (age: 15–19 years) (20% and 31%, respectively). Overall, neoplasia (23%) was the most common cause of acute third, fourth, and sixth cranial nerve palsies, followed by idiopathic cause (14%), inflammation (11%), and non-aneurysmal vascular contact (11%). Neoplasia was also the most common cause of sixth and third cranial nerve palsies (25% and 29%, respectively). The most common cause of fourth cranial nerve palsy was late decompensation in congenital fourth cranial nerve palsy (46%). A substantial proportion of pediatric and juvenile patients had serious pathologies for third, fourth, and sixth cranial nerve palsies. If nerve palsies are indicated, prompt diagnosis of etiologies using high-resolution MRI with contrast and laboratory work-up are important for this disease population.

Benign Recurrent Sixth Nerve Palsy in a Child

Article

Full-text available

Dec 2017

Benign recurrent sixth nerve palsy in children is rare. It typically occurs following viral illness or immunization, and prognosis is usually excellent. However, it is always a diagnosis of exclusion given the more serious alternative causes. Therefore, a thorough examination with brain imaging is recommended. The authors report a child with six recurrent episodes of isolated benign sixth nerve palsy.

Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

Article

Full-text available

Oct 2016

Background: Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015. Methods: We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores. Findings: We generated 9·3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17·2 billion, 95% uncertainty interval [UI] 15·4–19·2 billion) and diarrhoeal diseases (2·39 billion, 2·30–2·50 billion). Eight causes of chronic disease and injury each affected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-deficiency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that affected the greatest number of people in 2015 was anaemia, with 2·36 billion (2·35–2·37 billion) individuals affected. The second and third leading impairments by number of individuals affected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20–30% of total disability, largely attributable to nutritional deficiencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-deficiency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo. Interpretation: Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profile driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available.

Multiple Sclerosis Epidemiology in Middle East and North Africa: A Systematic Review and Meta-Analysis

Article

Full-text available

Jun 2015
NEUROEPIDEMIOLOGY

Multiple sclerosis (MS) is one of the most common neurological disorders and a leading cause of nontraumatic disability in young adults in many countries. Recent reports from the Middle East and North Africa have suggested a moderate to high risk of MS in these countries. A literature search was performed in August 2014 in MEDLINE, EMBASE, and IMEMR to retrieve original population-based studies on MS epidemiology in the Middle East and North African countries published between 1st January 1985 and 1st August 2014. We designed search strategies using the key words: MS, prevalence, incidence, and epidemiology. According to the inclusion criteria, 52 studies were included in this systematic review. McDonald's criteria were the most widely used diagnostic criteria in the studies. Most studies were conducted in single hospital-based centers with a defined catchment area. The female/male ratio ranged from 0.8 in Oman to 4.3 in Saudi Arabia. MS prevalence ranged from 14.77/100,000 population in Kuwait (2000) to 101.4/100,000 in Turkey (2006). The overall MS prevalence in the region was 51.52/100,000. The mean age at disease onset ranged from 25.2 years in Kuwait to 32.5 years in Northeastern Iran, with an overall estimate of 28.54 years. Recent advances in MS registries will allow nation-wide studies and temporal comparisons between countries, provided that age- and sex-standardized estimates are available. © 2015 S. Karger AG, Basel.

Multiple sclerosis causing a partial sixth nerve palsy

Article

Full-text available

Sep 2014

Cognitive dysfunction in pediatric multiple sclerosis

Article

Full-text available

Jul 2014

Cognitive and neuropsychological impairments are well documented in adult multiple sclerosis (MS). Research has only recently focused on cognitive disabilities in pediatric cases, highlighting some differences between pediatric and adult cases. Impairments in several functions have been reported in children, particularly in relation to attention, processing speed, visual–motor skills, and language. Language seems to be particularly vulnerable in pediatric MS, unlike in adults in whom it is usually preserved. Deficits in executive functions, which are considered MS-specific in adults, have been inconsistently reported in children. In children, as compared to adults, the relationship between cognitive dysfunctions and the two other main symptoms of MS, fatigue and psychiatric disorders, was poorly explored. Furthermore, data on the correlations of cognitive impairments with clinical and neuroimaging features are scarce in children, and the results are often incongruent; interestingly, involvement of corpus callosum and reduced thalamic volume differentiated patients identified as having a cognitive impairment from those without a cognitive impairment. Further studies about pediatric MS are needed in order to better understand the impact of the disease on brain development and the resulting effect on cognitive functions, particularly with respect to different therapeutic strategies.

Sex differences and subclinical retinal injury in pediatric-onset MS

Article

Jun 2016

Objective: To assess retinal ganglion cell (RGC) injury and sex differences in axon loss in pediatric multiple sclerosis (MS). Methods: This is a cross-sectional evaluation of consecutive pediatric MS subjects and controls. Eyes with acute optic neuritis (ON) within 6 months of visit were excluded. Spectral domain optical coherence tomography (OCT) included peripapillary ring and macular scans with post-acquisition segmentation of retinal layers using automated software (Heidelberg v1.8.6.0). Generalized estimating equations (GEEs) measured associations of sex, history of ON, disease duration, and age with OCT outcomes. Results: In all, 53 MS subjects (100 eyes, median disease duration = 1.0 years, interquartile range (IQR) = 0.3, 2.5) were compared to 19 control subjects (38 eyes). Eyes with history of ON showed reduced retinal nerve fiber layer (RNFL: -26.8 µm, 95% confidence interval (CI) = -38.9, -14.8, p < 0.001) and 26% lower ganglion cell layer (GCL) volumes (-0.12 mm(3), 95% CI = -0.16, -0.072, p < 0.001) compared to control eyes. Non-ON MS eyes had lower temporal RNFL (-11.9 µm, 95% CI = -18.6, -5.3, p < 0.001) and GCL volumes (-0.036 mm(3), 95% CI = -0.06, -0.011, p = 0.004) than control eyes. In MS eyes, males versus females had lower global RNFL (-9.4 µm, 95% CI = -17.4, -1.33, p = 0.022) and in ON eyes had lower temporal quadrant RNFL (-9.6 µm, 95% CI = -15.1, -4.15, p = 0.001). Conclusion: Subclinical retinal injury occurs in pediatric-onset MS patients without a history of ON. As in adult-onset MS, substantial GCL thinning is present in eyes with prior ON. Finally, greater retinal axonal injury occurs in boys compared to girls.

Multiple Sclerosis in the Very Young: A Case Report and Review of the Literature

Article

Feb 2016

Onset of multiple sclerosis (MS) in the very young (<10 years) is uncommon. We describe a 2 year old girl with MS, the youngest reported case in the USA. She presented to an outside hospital with acute onset of ataxia on three occasions before presenting to our institution, initially misdiagnosed as acute disseminated encephalomyelitis and treated with intravenous methylprednisolone. MRI of the brain during each presentation revealed new areas of demyelination. Initial cerebrospinal fluid (CSF) studies and MRI of the spine were normal. Repeat MRI of the brain at our institution, 7 months later, revealed new demyelinating lesions and CSF analysis revealed elevated myelin basic protein, negative oligoclonal band and neuromyelitis optica immunoglobulin and normal IgG synthesis. Her clinical presentation with multiple relapses and new MRI findings validated the diagnosis of MS.

Histologie de la sclérose en plaques

Article

Jan 1868

J.M. Charcot

Multiple Sclerosis

Article

Oct 2008

Multiple sclerosis is primarily an inflammatory disorder of the brain and spinal cord in which focal lymphocytic infiltration leads to damage of myelin and axons. Initially, inflammation is transient and remyelination occurs but is not durable. Hence, the early course of disease is characterised by episodes of neurological dysfunction that usually recover. However, over time the pathological changes become dominated by widespread microglial activation associated with extensive and chronic neurodegeneration, the clinical correlate of which is progressive accumulation of disability. Paraclinical investigations show abnormalities that indicate the distribution of inflammatory lesions and axonal loss (MRI); interference of conduction in previously myelinated pathways (evoked electrophysiological potentials); and intrathecal synthesis of oligoclonal antibody (examination by lumbar puncture of the cerebrospinal fluid). Multiple sclerosis is triggered by environmental factors in individuals with complex genetic-risk profiles. Licensed disease modifying agents reduce the frequency of new episodes but do not reverse fixed deficits and have questionable effects on the long-term accumulation of disability and disease progression. We anticipate that future studies in multiple sclerosis will provide a new taxonomy on the basis of mechanisms rather than clinical empiricism, and so inform strategies for improved treatment at all stages of the disease.