Amsterdam Medical Student journal (AMSj) | Volume 13

ARTICLE | CHANGING PERSPECTIVES | TRIAL AND ERROR | SOLVING STATISTICS INTERVIEW | CLINICAL IMAGE | RADIOLOGY IMAGE | EXPERT OPINION

Amsterdam Medical Student journal

EDITION 13 | OCTOBER 2018

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Index 2 Editorial 3

Finding the best target for deep brain stimulation in treating gait and postural instability in Parkinson’s disease: a systematic review | C. Krijger, Prof. dr. R.M.A de Bie, MD PhD

11

Interview | Dr. R. Krage

13

Radiology image | A 30-year-old man with ulcerative colitis and abnormal serum liver biochemistry tests

14

Solving statistics | Regression analysis

15

Trial and error | Trial before en error after

16

Changing perspectives | Depression, opposing ancient tradition

17

Expert opinion | Thirty minutes of exercise a day keeps the doctor away?

18

Clinical image | A periocular rash

20

Answers | Radiology image

21

Answers | Clinical images

AMSj Vol. 13 | Oct 2018

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Editorial Science is the fundament of our health care and has led to many great breakthroughs, but the costs of doing research are high and without a lot of money, there is no research possible. But where does the money come from? In the Netherlands, we can distinguish three sources: the first financial flow, responsible for about 66% of the total income, is a free disposable income coming from our government. Research groups can do whatever they desire with the money coming from the first financial flow. The second financial flow derives from subsidy institutions and the third one originates from commercial and public clients.1 Nowadays less money is available from the first financial flow and universities, and more and more research is funded by companies or social institutions. However, scientists suffer from increasing influences by the financier. ‘He who pays the piper calls the tune’ is as the saying goes, and financiers urge scientists to change the scope of their research, adjust results or present results more favorably.1,2 They might even strongly request scientists not to publish their data, which is in contrast to the professional code of the ‘Koninklijke Nederlandse Akademie van de Wetenschap’, stating that scientists have to publish their data despite the outcome.1,2 Open science is at stake and money shortages makes independence and the right to publish sensitive concepts.

Young scientist submitting their manuscript to AMSj have mostly performed their research without any funding at all. We appreciate the effort they have made to accomplish their papers. Therefore, as with every edition, we are happy to share our content with you.

In this volume, C. Krijger and R. de Bie reviewed the efficacy of deep brain stimulation in the subthalamic nucleus versus deep brain stimulation in the globus pallidus internus in patients with Parkinson’s disease. N. Rosenberg and N. Rol show their expert’s opinion on lifestyle interventions in preventing cardiovascular diseases and critically assess an article about the association between the amount of exercise one commits and central arterial stiffness. Let our Solving Statistics help you understand a regression analysis and check out the

diagnosis in a 30-year-old man with fatigue and elevated levels of alkaline phosphatase and aminotransferases in our radiology image. We hope you enjoy reading our 13th edition of AMSj.

Vera de Jonge Student Editor-in-Chief (VUmc)

Accountability: data in this editorial is based on three articles about the undesirable influence of lenders on scientific research published in the Dutch newspaper NRC this summer.1,2,3 1.

2.

3.

F. van Kolfschooten, C van de Wiel, M Huygen. De geldschieter wil wel zelf wat aan het onderzoek hebben.

NRC. August 31, 2018. Available via: https://www.nrc. nl/nieuws/2018/08/31/de-geldschieter-wil-wel-zelf-wataan-het-onderzoek-hebben-a1614919 F. van Kolfschooten, C van de Wiel, M Huygen.

Overheid dwingt wetenschappers onafhankelijkheid op te geven. NRC. September 3, 2018. Available via: https://www.nrc.nl/nieuws/2018/09/03/ambtenaren-hebben-het-laatste-woord-a1615173 F. van Kolfschooten, C van de Wiel, M Huygen. Voor een klein bedrag koopt een bedrijf veel invloed. NRC. September 5, 2018. Available via: https://www.nrc.nl/ nieuws/2018/09/05/voor-klein-bedrag-koopt-bedrijfveel-invloed-a1615509

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3 ARTICLE

Finding the best target for deep brain stimulation in treating gait and postural instability in Parkinson’s disease: a systematic review C. Krijger1 and prof. dr. R.M.A de Bie1 1. Department of Neurology, Academical Medical Center, University of Amsterdam, Amsterdam, the Netherlands Correspondence: c.krijger@amc.uva.nl

ABSTRACT

O B J E C T I V E Parkinson’s disease (PD) is a neurodegenerative disease occurring mostly around the age of 60. Besides medical treatment, deep brain stimulation (DBS) is an option for treatment. Currently, DBS has two targets: the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Both targets have only been compared in efficacy on motor symptoms and tremor reduction. The current systematic review investigates the clinical efficacy of the two targets on improvement in gait and postural instability.

M E T H O D S Clinical trials were searched that compared DBS of the STN versus DBS of the GPi on patients with PD. Outcomes were changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) scores that included gait and/or postural instability. These changes were evaluated in the on-medication and off-medication phases.

R E S U LT S Six studies published between 2001 and 2015 containing 506 PD patients were included. Five studies were of high quality, and one of fair quality. In five studies DBS was done bilateral, meaning that the implantation of the electrodes in the brain was done on both sides (one in the right half, and one in the left half of the brain). In the off-medication phase, STN-DBS resulted to be more effective for gait and balance than GPi-DBS. STN-DBS seemed to result in a lower dose of L-dopa than GPi-DBS. In the on-medication phase there seems to be no difference between the two targets.

C O N C L U S I O N STN-DBS might be more effective than GPi-DBS in treating gait and postural instability symptoms in the off-medication phase. However, more trials are needed in order to make recommendations for clinical practice.

INTRODUCTION

Parkinson’s disease (PD) is a neurodegenerative disease. Neuronal damage is probably caused by increased accumulation of Lewy bodies, which firstly affect the basal ganglia.1, 2 The main symptoms are rest tremor, rigidity, bradykinesia and loss of postural reflexes.3, 4 Normally, the age of onset is around 60 years old. When people under the age of 40 develop PD, it is called young-onset PD.5 Besides tremor, walking difficulties are often seen in PD due to the presence of stiffness, freezing of gait and lack of stability.4 The main therapy for PD is pharmacological treatment, with L-dopa being the main drug of choice.

However, in the long term, complications like dyskinesia can be seen. Also, motor symptoms may not be reduced enough. This can be explained by the continuous degeneration of neurons in the brain which causes a progressive development of symptoms. In these cases, the L-dopa dose has to

be increased in attempt of remaining the symptoms controlled, until this is not sufficient anymore.

Deep brain stimulation (DBS) can serve in those occasions as an alternative option. It is well known that for patients with PD, DBS is effective for several motor symptoms.6-10 DBS is based on electrical current to the basal ganglia, that are inhibited by these impulses.11, 12 There are several brain areas where DBS is applied these days. One of the first brain areas ever used for DBS is the ventral intermediate nucleus (VIM). This area is mostly effective in only treating tremor symptoms. The nucleus subthalamicus (STN) is currently the preferred area for DBS in PD, treating many symptoms besides tremor.8, 9, 13 But it is known if this is the preferred location for each specific symptom. The globus pallidus internus (GPi) is also used as a target for DBS in treating several symptoms. PD is a heterogeneous disease, which means that the symptoms patients

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experience may differ greatly. This also counts for the effect of DBS.14, 15 Many trials have been performed comparing STN and GPi as DBS targets. Differences in overall UPDRS scores have been investigated in multiple studies. Yet, specific comparison of efficacy on gait and postural instability is still missing. Another point of interest is to figure out whether the effect is bigger in the on-medication phase (on-phase), where the patients still takes L-dopa, or off-medication phase (off-phase), where the patient does not take any L-dopa.

The aim of this systematic review is to give clinical information whether DBS of the STN or GPi provides better improvement for gait and postural instability. The results of this study could be used as a recommendation for clinical practise when choosing which brain area suits best as target for DBS in PD patients when focussing on gait and stability symptoms.

The hypothesis of this systematic research is STN being a more effective target area for DBS focussing on gait and postural stability symptoms.

METHODS LITERATURE SEARCH

A systematic literature search was performed in PubMed and Cochrane Library from 23 November 2017 till 18 December 2017, publications of all dates were included. The specified Medical Subject Headings (MeSH) search terms used were “Electric stimulation therapy”, “Parkinson’s Disease”, “Subthalamic nucleus”, and “Globus pallidus”. Because relatively new studies may not have been assigned several MeSH terms yet, each of the terms that were used as MeSH term were also used as a [tiab] keyword in the search. Also, corresponding keywords of these search terms were used to aim for sensitivity as high as possible.

INCLUSION/EXCLUSION CRITERIA

The following inclusion criteria were used: 1) PD patients; 2) treatment with STN-DBS or GPi-DBS; 3) motor outcomes assessed with UPDRS score; 4) English language; 5) clinical trials. The following exclusion criteria were used: 1) duplicate studies with the same research group and (partly) same

subject group; 2) UPDRS scores for gait/postural instability not available; 3) no full text available.

Studies were included regardless of their publication date.

STUDY SELECTION

All duplicate studies were excluded. Title and abstract of the studies were assessed by the first author. Thereafter, full texts of the potential studies were evaluated for inclusion and exclusion criteria.

DATA EXTRACTION

Information extracted from eligible studies contained name of first author, year of publication, number of subjects used in the study, analysis of the subjects group, sex ratio (male/female), mean age, disease duration, duration of follow-up, number of centres and geographical location of the study, outcomes (type analysed, UPDRS items, UPDRS scores for gait and/or postural instability and changes in L-dopa dose) OUTCOME MEASUREMENTS

The UPDRS score is a widely used outcome measure for motor performance in PD patients. A low score in UPDRS stands for better function. When improvement is observed, measurement comparisons of baseline and follow up UPDRS scores will give a negative value.21 There are several UPDRS items for different motor symptoms. To answer the research question, in this review the UPDRS motor score changes for the items gait and/or postural instability were used as the primary outcome. The secondary outcome was reduction in medicine use

by PD patients.

EVIDENCE QUALITY ASSESSMENT

The PEDro scale, a valid scale meant to measure the methodological quality of randomized controlled trials, was used to assess the quality of the included studies.16 It is based on the Delphi list developed by Verhagen et al. at the Department of Epidemiology at the University of Maastricht in 1998. The PEDro scale consists of 11 criteria to evaluate the quality of the study. Each criterion can be answered with yes or no. For more detailed information, see FIGURE 2.

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RESULTS

DBS PARAMETERS

SEARCH AND STUDY SELECTION

The search resulted in 783 studies. Fifty studies were excluded for being duplicates. 658 articles were excluded for not being clinical trials. Based on title and abstract 37 studies were excluded for not meeting the remaining inclusion and exclusion criteria. 32 studies were excluded after screening full texts on inclusion and exclusion criteria, mostly because of the studies having no individual UPDS scores available for neither gait nor postural instability. Eventually, six clinical trials were included in the review (FIGURE 1).

CHARACTERISTICS OF THE STUDIES

Six studies, published between 2001 and 2015, included a total of 506 patients. Number of included patients per study ranged from 2313 to 1379.

The mean patient age was 60.5 years. There was a higher proportion of male subjects, ranging from 51 to 86. Mean disease duration ranged from 11.9 to 15.6 years.

Database search (PubMed) 59 studies

The DBS placement was bilateral in five of the six studies (TABLE 3).6. 9. 13 The GPi group had a larger mean voltage, larger mean pulse width and larger mean frequency, compared to the STN group.

QUALITY ASSESSMENT

According to the PEDro scale, five studies were of high quality (score 6-10)6, 8, 9, 13, 18 and one of fair quality (score 4-5)7 (TABLE 2). No study was of poor quality (score 0-3).

CLINICAL OUTCOMES

FOLLOW UP TIME

Differences in follow up time between the studies was observed, ranging from a half year6,18 to 3-4 years7, see also TABLE 3.

UPDRS SCORE (ON-MEDICATION)

For gait and postural instability together, two

Database search (COCHRANE) 66 studies

125 clinical trials

50 duplicate studies excluded 75 clinical trials

38 clinical trials

6 clinical trials included in the review

37 studies excluded by screening on title and abstract • 16 Studies had no motor outcomes • 8 Studies only neuropsychological outcomes • 5 Studies had no DBS • 6 Studies only STN • 2 studies only GPi 32 Studies excluded by screening on full text • 22 Studies had no individual UPDRS scores available for gait and/or postural instability • 8 Studies were the subjects were the same • 1 Study was in Spanish • 1 Study had only short term (in hours) results

FIGURE 1 Search flowchart.

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6 ARTICLE

studies showed a slightly better improvement in STN than GPi (UPDRS -0.5 vs 0, and -0.6 vs -0.5), but these differences were not statistically significant (p=0.32 and p=0.71).8, 13 St. George et al. showed a statistically significant larger improvement for GPi compared to STN (-5.5 vs -4.9, p value <0.001)17 (TABLE 3).

Rodriguez et al. showed a minor better/larger improvement in GPi compared to STN for item 29 (gait) (-0.1 vs +0.3) and item 28 (postural instability) (-0.1 vs +0.1), with only the UPDRS score difference being statistically significant for item 28 (posture)(p<0.0001).7 Obeso et al. showed a slightly better/larger improvement in GPi compared to STN for item 28 (-0.7 vs -0.3) and 29 (-0.4 vs -0.3) (TABLE 3).

UPDRS SCORE (OFF-MEDICATION)

For the off phase, three studies8, 9, 13 showed a larger UPDRS improvement in the STN group for gait and postural instability, with one showing statistically significant improvement.8 One study showed larger improvement in GPi.19 The P value of this result was not available, making it unclear whether this result can be interpreted as statistically significant or not.Two studies6, 7 measured individual items for postural instability and gate (item 28 and 29). Both studies had no P values available. Rodri-

guez et al. showed a larger improvement for STN item 28 (-0.8 vs -0.6) and for item 29 (-1.2 vs -0.7).

Obeso et al. showed a better/larger improvement for STN item 28 (posture) (-1.2 vs -0.8) and item 29 (gait) (-1.5 vs -0.9) as well (TABLE 3).

CHANGES IN MEAN L-DOPA DOSE

After undergoing DBS, most PD patients had a decrease in levodopa dose.6, 8, 9, 13, 18, 21 Five of the six studies showed a larger reduction in L-dopa dose at follow-up after DBS of STN.6, 8, 9, 13, 18 Yet just one study shows a statistical significant decrease of L-dopa dose in STN (P=0.01), with a difference in change of dose of 338 mg.8 Two studies showed the difference between STN and GPi in L-dopa changes to be not statistically significant.2,3 (TABLE 4).

DISCUSSION

This study shows that STN DBS could be a preferred target for patients with Parkinson to improve gait and postural instability symptoms in the off-medication phase.

All six included studies showed that both STN and GPi DBS targets are effective for gait and postural instability. In five studies STN-DBS seemed to be more effective in the off-phase6-9, 13, two of them showing the difference to be statistically significant.7 ,8 Two other studies had no P values availNo

1. Eligiblity criteria were specified 2. Subjects were randomly allocated to groups (in a crossover study, subjects were randomly allocated an order in which treatments were received) 3. Allocation was concealed 4. The groups were similar at baseline regarding the most important prognostic indicators 5. There was blinding of all subjects 6. There was blinding of all therapists who administered the therapy 7. There was blinding of all assessors who measured at least one key outcome 8. Measures of at least one key outcome were obtained from more than 85% of the subjects initially allocated groups 9. All subjects for whom outcome measures were available received the treatment or control condition as allocated or, where this was not the case, data for at least one key outcome was analysed by â&#x20AC;&#x153;intention to treatâ&#x20AC;?

10. The results of between-group statistical comparisons are reported for at least one key outcome 11. The study provides both point measures and measures of variability for at least one key outcome

FIGURE 2 PEDro scale.

Oct 2018 | AMSj Vol. 13

Yes

Where:

Katz 2015 N=137

Odekerken 2013 N=63

Rodriguez* 2005 N=49

Anderson 2005 N=12

St. George** 2014 N=14

Obeso 2001 N=91

1

2

3

4

5

6

18

1

1

8

5

13

No. of centers

USA

USA

USA

Spain

Netherlands

USA

Country

AMSj Vol. 13 | Oct 2018 At least 2 cardinal features of parkinsonism, good levodopa response, at least score of 30 UPDRS off med.

-

Age between 20 and 80, PD, with bradykinesia +rigidity

-

>18 y, idiopathic PD, at least 1 symptom despite treatment

PD, H&Y score >2, levodopa responsiveness, >3 hours poor symptom control/function

Inclusion criteria

9

9

7

5

9

8

Pedro scale score

UPDRS, % time walking with poor mobility

ABC, BaG, PIGD (UPDRS)

UPDRS

UPDRS 2 & 3, time with bad mobility

ALDS, UPDRS

UPDRS 2 & 3 off

Analized outcomes

Bilateral, 36

14

Bilateral, 11

Bilateral, 20

Bilateral, 65

Bilateral,

GPi site + no. randomized

Bilateral, 91

14

Bilateral, 12

Bilateral, 49

Bilateral, 63

Bilateral

STN site + no. randomized

-

-

Extension study

Follow up of initial study

Medication lower in STN group

Only PIGD group analyzed

Notes

*This article did not report inclusion and exclusion criteria. **This study did not show inclusion nor exclusion criteria either. Also it was not mentioned in the study whether the electrodes were implanted ipsilateral or bilateral.

Abbreviations: UPDRS= United Parkinsonâ&#x20AC;&#x2122;s Disease Rating Scale. ABC= Activities-specific Balance Confidence, BaG= Balance and Gait scale, PIGD Postural instability and gait disability items (27,28,29,30) of the UPDRS score.

TABLE 2 Intervention characteristics per study.

Author,year, number of subjects

Study no.

ARTICLE 7

8 ARTICLE

able.6,7 One study found GPi-DBS to be more effective in the off-phase (no P value available).18 This could mean that STN-DBS is more effective for gait and postural instability in the off-phase.

For the on-phase, the outcomes between STN and GPi were similar.

Five of the six studies showed a larger reduction in L-dopa dose at follow up after DBS of STN, 6, 8, 9, 13, 18 yet just one study shows a statistical significant decrease of L-dopa dose in STN (P=0.01).8 There was a higher proportion of male subjects, ranging from 51 to 86%. This is in agreement with the fact that PD is more common in men than in women.24, 25 Xu et al. described that STN could be the preferred target for DBS for the improvement of general motor symptoms in the off-phase, while GPi-DBS was associated with a better improvement in the on-phase. Our current review should be interpreted as an additional source of information about whether this conclusion could also account for the improvement of one specific group of symptoms (gait and postural stability). Our systematic review supports the conclusion of Xu et al.

One of the limitations of this study is that the items used to measure UPDRS are different in some studies. For example, Odekerken et al. used items 27, 28, 29 and 30 to measure the UPDRS score of gait and postural instability combined. Anderson et al. used items 18, 28, 29, 30 for the same purpose.

Even though the quality of both studies according to the PEDro score was good (FIGURE 2), and both studies used three identical UPDRS items, one item is in each study different. This could have a negative effect on the results of this systematic review.

Further, in the paper of Katz et al. the subjects were divided into three groups. A tremor dominant (TD) group, and intermediate (I) group, and a postural instability and gait difficulty (PIGD) group. For this study, members of the PIGD group seemed to be the most relevant and only the outcomes of this group were measured. This could have led to selection bias, because the other group could have had different response to either STN or GPi DBS.

Also, the number of subjects for the individual PIGD group was not available.

As can be seen in TABLE 2, the follow up time for the measurements is different in almost each study.

Therefore, comparison of the differences in UPDRS outcomes might be incomparable.

Further, not all P values are available for each study (TABLE 2). This can be explained by the fact that some of the studies used only P values to test the statistical significance for the changes in UPDRS scores between baseline and follow up measures for each DBS target, instead of using also P values for the differences in UPDRS changes between STN and GPi.6, 7, 18 One systematic review concluded that DBS of STN could be more effective in treating motor symptoms than GPi, using total UPDRS scores as outcome.23 This review is in accordance with our study, and provides results to make a more specific statement regarding just one specific motor problem (i.e. gait and postural instability).

The outcomes of our review could be used as a tool when deciding which target should be chosen for DBS in treating PD. These outcomes are not meant to decide directly whether STN of GPi DBS should be done on a patient, but rather help to make a decision in which the opinion of the patient is also very important. The patient should be informed about the possible achievements that can be reached with this therapy, but should also be aware of the possible side effect and the variation in DBS effect per person.

There was one study which did not make it through the inclusion and exclusion criteria, but is interesting to discuss. Moro et al. showed that five years after DBS nine of the 35 patients in the STN group had unresolved gait disorders as adverse effect, while only one of the 16 patients in the GPi suffered from this side effect. Also five of the 35 patients in the STN group suffered from unresolved balance disturbances, while only one of the 16 patients in the GPi group suffered from this side effect after five years. This study may suggest that undergoing STN DBS could induce a higher risk of unresolved adverse effects in gait and balance.

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9 ARTICLE Study

Follow up (y)

UPDRS items

UPDRS change for gait and postural instability since baseline (SD) On-phase STN

Off-phase GPi

P value

STN

GPi

P value

13, 14, 15, 29, 30 -

-

-

-2.0 (4.0)

-0.9 (3.8)

n.s

Odekerken 2013 1 N=63

27, 28, 29, 30

-0.6 (3.3)

-0.5(1.8)

0.71

-2.7 (3.3)

-0.7(3.0)

0.007

Rodriguez 2005 N=49

3-4

28

+0.1

-0.1

-0.8

-0.6

29

+0.3

-0.1

-1.2

-0.7

Anderson 2005 N=12

1

18, 28, 29, 30

-0.5

0**

-3.5

-3.0

St. George 2014 N=14

0.5

27, 28, 29, 30

-4.9

-5.5

-2.1

-2.7

Obeso 2001 N=91

0.5

28

-0.3

-0.7

-1.2

-0.8

29

-0.3

-0.4

-1.5

-0.9

Katz* 2015 N=137

2

0.32

0.12

TABLE 3 Outcomes of each study.

Change in UPDRS scores for gait and/or postural instability from baseline till follow up assessed for STN-DBS and GPi-DBS. P values indicate whether the difference between these changes are significant (P<0.05) or not. Not all the studies provided standard deviations for the UPDRS score changes.

Abbreviations: UPDRS= United Parkinsonâ&#x20AC;&#x2122;s Disease Rating Scale, y=years, n.s= not significant, on/off-phase= with or without medication, SD= standard deviation. *Katz et al. did not have data available for UPDRS scores in the on-phase. **Anderson et al. did not show any change in the on-phase for GPi. Study

STN

GPi

P value

Katz* 2015 N=137

-577.2 (815.7)

-259.0 (657.5)

*

Odekerken 2013 N=63

-546 (561)

-208 (521)

0.01

Rodriguez 2005 N=49

-589 (659)

-1418 (1252)

*

Anderson 2005 N=12

-38%

-3%

0.08

St. George 2014 N=14

-374

-317

n.s

Obeso 2001 N=91

-454**

+29.1

*

TABLE 4 Mean difference in changes of levodopa dose (mg) from baseline to follow-up Changes in levodopa dose can be seen when baseline compared with follow up.

Abbreviation: N.s = not significant. *Katz et al., Rodriguez et al. and Obeso et al. had no P values available for the comparison in L-dopa change between STN and GPi DBS. **Obeso et al. only showed a statistically significant change in L-dopa dose after follow up for the DBS of STN (P<0.001).

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10 ARTICLE

When deciding with a patient which target is best to use for DBS, it should be important to know what the patient’s view is on the possibility of developing such unresolved adverse effects.

Medication reduction with the help of DBS could reduce the risk of side effects that could cause these. Medication reduction could also be a point of view to consider when deciding the most effective target for DBS in PD when focusing on gait and postural instability. There seems to be a trend for STN to reduce levodopa dose more than GPi. More trials should be performed with sufficient statistical test for difference between STN and GPi for changes in levodopa use to solve this uncertainty.

DBS of the STN and GPi are both effective in reducing gait and postural instability symptoms.

In the on-medication phase, results are similar between STN and GPi as a DBS target. In the off-medication phase, STN as a DBS target seems to be more effective according to most of the studies. These findings could be used as indication for physicians in choosing the best target for DBS in their PD patients. More trials with larger groups comparing STN with GPi DBS should be done to investigate this hypothesis.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

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Mov Disord, 2014. 29(7): p. 949-53.

Maher, C.G., et al., Reliability of the PEDro scale for rating quality of randomized controlled trials. Phys Ther, 2003. 83(8): p. 713-21.

Martinez-Martin, P., et al., Parkinson’s disease severity levels and MDS-Unified Parkinson’s Disease Rating Scale. Parkinsonism Relat Disord, 2015. 21(1): p. 50-4.

Kim, J.H., et al., Effect of Subthalamic Deep Brain Stimulation on Levodopa-Induced Dyskinesia in Parkinson’s Disease. Yonsei Med J, 2015. 56(5): p. 1316-21.

Xu, F., et al., Deep brain stimulation of pallidal versus subthalamic for patients with Parkinson’s disease: a meta-analysis of controlled clinical trials. Neuropsychiatr Dis Treat, 2016. 12: p. 1435-44.

Xu, H., et al., Subthalamic nucleus and globus pallidus internus stimulation for the treatment of Parkinson’s disease: A systematic review. J Int Med Res, 2017. 45(5): p.

1602-1612.

Moro, E., et al., Long-term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson’s disease. Mov Disord, 2010. 25(5): p. 578-86 Moisan, F., et al., Parkinson disease male-to-female ratios increase with age: French nationwide study and meta-analysis. J Neurol Neurosurg Psychiatry, 2016. 87(9): p. 952-7.

Miller, I.N. and A. Cronin-Golomb, Gender differences in Parkinson’s disease: clinical characteristics and cognition. Mov Disord, 2010. 25(16): p. 2695-703.

Oct 2018 | AMSj Vol. 13

11 INTERVIEW

Dr. R. Krage Interviewed by S. Rozemeijer

Area of expertise: Anesthesiology, Pre-hospital care, Emergency Medicine, Crisis Resource Management and Human factors in medical care.

Current position: Anesthesiologist and chairman of the residency program Anesthesiology at the Amsterdam UMC, location VUmc. Did you always have the ambition to become an anesthesiologist? ‘‘Since I was ten years old I knew I wanted to become the first medical doctor in my family. I started my medical education in Hannover, Germany.

During my study I became a paramedic and was a paramedic instructor as side job. It made me enthusiastic for acute medicine, in which immediate feedback on medical interventions impressed me the most. Therefore, trauma surgery fascinated me and made me almost decide to choose this specialist field. However, it takes much time until residents are allowed to carry out procedures by themselves. In addition, the long shifts discouraged me.

As a result I waived my field of interest and made my decision to choose for the anesthesia residency program.’’

You graduated and worked as an anesthesiologist in Germany. Why did you decide to move away? ‘‘My career as an anesthesiologist started in Germany as a staff member and later on as a senior staff member (Oberarzt). As ‘‘Oberarzt’’ I supervised the group of staff members and residents, a job position that does not exist in the Netherlands.

Due to less satisfying working conditions in terms of shifts and salary in Germany, I decided to move to the Netherlands hoping that it would bring me more job satisfaction. When acting as coordinator of 18 operation rooms in the VU Medical Center it became clear that our staff members work more independently and that giving orders was less accepted. I could easily get used to this working culture which differed a lot from the more hierarchic culture I was raised with in Germany. And up to

Dr. R. Krage as helicopter flight physician

now, I am still working with a lot of pleasure at the Amsterdam UMC, location VUmc!’’ Do you have any research experience? ‘‘I completed my dissertation in Hannover, Germany. In Germany, writing a dissertation was different from the way a PhD-thesis is constructed in the Netherlands. It was mostly based on one major project, rather than several publications as we are used to now. Fortunately, I could hold the title PhD when I moved to the Netherlands. Currently, I am very interested in setting up a research line on the impact of teamwork on patients’’ outcome.

I am convinced that the, so called, ‘‘human factor’’ plays a major role in patient care. The human factor is even as important as our medical knowledge and clinical experience and is still a major contributor to errors we make. Therefore, promoting

AMSj Vol. 13 | Oct 2018

12 INTERVIEW

awareness about the human factor is inevitable in daily clinical practice.’’

Why is simulation training so important? ‘‘When I became a paramedic instructor I had to take a final exam that was designed as a clinical scenario. This method inspired me and still has an important place in my medical education and training. It teaches medical students and young doctors to place themselves in vulnerable positions in which they are able to learn about communication, teamwork and other human factor issues. Simulation training sessions enable us to keep learning and developing ourselves, a process that should never stop. We have to improve our skills continuously to enhance our changeable daily clinical work. There is still much to achieve but the beginning is there!’’

‘‘Practice what you preach.’’

Do you have specific goals for the future? ‘‘I recently became chairman of the residency program Anesthesiology, a great new step in my career. Unfortunately, I had to put my work as helicopter flight physician behind me. I really loved this job, even though I have been confronted with impressive situations that I will not easily forget.

Now it is time to pass the baton to our young anesthesiologists. As chairman I want to guide our residents, improve their medical training and monitor the process. I am currently busy to achieve the Senior Teaching Qualification (STQ) in order to continue developing our education program.’’

CURRICULUM VITAE 1968 Born 1987-1995 Medicine: Medizinische

Hochschule Hannover (MHH),

Germany 1989 Registration as paramedic 1991 Registration as paramedic instructor 1998 Dissertation: MHH, Germany:

‘Einfluss der medikamentösen

Stressulkusprofylaxe auf die

zirkadiane Rhythmik der

intragastralen Azidität bei

beatmeten Intensivpatienten.’

1995-2002 Resident in anesthesiology 2002 Registration as anesthesiologist 2002-2006 Staff member anesthesiology,

Universitӓtsklinikum

Düsseldorf, Germany 2007-present Senior staff member

anesthesiology, VUmc

Amsterdam 2007-present Head Simulation Center ADAM,

VUmc Amsterdam 2009-2017 Helicopter flight physician,

member of the ‘Mobiel Medisch

Team (MMT)’ 2018- present Chairman of the residency

program Anesthesiology

What would you advise students? ‘‘An important lesson that I have learned and I want to impart to all students and doctors is to ‘practice what you preach’ and most importantly to believe in ‘lifelong learning!’’

Dr. R. Krage. Photo by DigiDaan.

Oct 2018 | AMSj Vol. 13

13 RADIOLOGY IMAGE

A 30-year-old man with ulcerative colitis and abnormal serum liver biochemistry tests T.L. Kortlever and K. de Wit

CASE

QUESTION 1

A 30-year-old man was found to have elevated levels of alkaline phosphatase and aminotransferases during a routine check-up (around 2-3 times the upper limit of normal). Three years ago, he was diagnosed with ulcerative colitis.

Except fatigue, he did not experience any other symptoms. He denied usage of intravenous drugs, tattoos, unprotected sexual contact or transfusions. His alcohol consumption did not exceed average quantities. Even after stopping all possible liver toxic medication, the liver biochemistry tests remained elevated. An ultrasound of the liver was performed and showed a slight thickening of the bile duct wall.

After careful consideration you decide a Magnetic Resonance Cholangiopancreatography (MRCP) should be performed (FIGURE 1). What abnormality is found on the images?

A. Gallstones B. Extrahepatic mass C. Bile duct strictures and dilatations D. Hepatic steatosis

QUESTION 2

What is the most likely diagnosis considering the MRCP findings and the clinical history?

A. Autoimmune hepatitis B. Primary Biliary Cholangitis C. Primary Sclerosing Cholangitis

QUESTION 3

What other diagnostic tool is the most accurate in detecting this disease?

A. Endoscopic Retrograde

Cholangiopancreatography (ERCP) B. Detection of auto-antibodies C. Liver biopsy D. CT-scan

FIGURE 1 Image taken from a MRCP. Courtesy of: Amsterdam UMC. AMSj Vol. 13 | Oct 2018

?

Answer on page 20

14 SOLVING STATISTICS

Regression analysis S.W. de Jonge, MD, Clinical epidemiologist and PhD candidate, Department of Surgery, Amsterdam UMC

‘’ALL MODELS ARE WRONG, SOME MAY BE USEFUL’’ - GEORGE BOX Most scientist that use data to get a better understanding of the world around them (i.e. medicine, political sciences, social sciences, economics etc.) use statistics. A very common technique within statistics is regression analysis. Regression analysis is a form of statistical modeling used to estimate relationships between two or more variables.

Simple examples could be the association of packyears on lung function or millimeters (mm) rain on umbrella sales. More complex examples can be found in the Framingham risk score, or in the algorithm Netflix uses to predict your next bingewatch. There are many forms of regression analysis with each its own applications, underlying assumptions, benefits and limitations. Here I will try to introduce some of the basic concepts of simple linear regression.

The graph below represents mm of rain (horizontal axis) and umbrella sales (vertical axis). The dots represent data points of previous rainfall and umbrella sales on previous days. (i.e. at 22mm of rain about 100 umbrellas were sold). Tomorrow 50 mm of rain is expected. There is no dot at 5mm of rain so the amount of umbrellas sold at such rainfall is unknown. What is your best estimate of umbrella sales for tomorrow? Most people will intuitively estimate the amount of umbrellas sold based on the information they see. Deliberate or subconscious they will draw an imaginary line across the dots and measure its height at 50mm. For the sake of the exercise I urge you to actually draw a straight line across the dots. In essence, this is regression. We estimate an unknown value based on the information we do have. The linear function F(X)=AX+B may be used to describe the imaginary line and to calculate our estimate of F (umbrellas sold) for any value of X (mm rainfall). A is the slope of your line. B is the intercept, the point where our imaginary line crosses the zero value. This represents the umbrella’s we will sell anyway, regardless of

rain. But whatever imaginary line you draw, no line will perfectly hit every dot. Some dots will be missed and some will be hit. The distance between each dot and the line that helped us estimate umbrella sales at 50mm rain is called the residual error. The actual equation of our simple linear regression should include this error as follows F(X) = AX+B+e, were e represents the residual error.

Now all your lines may be similar but difference will be present. How do we pick the best line for our regression? Here, the residuals come in handy.

As we strive for the best estimate for umbrella sales for all rainfalls we want to minimize residual errors. To find the optimal line we choose the value for A & B that results in the lowest sum of squared residual errors. Squared, because otherwise or positive and negative errors would cancel each other out and we could still end up with a very poor estimate. By following these steps you would get a reasonable model for umbrella sales and rainfall. But be aware, we are making assumptions. More on this later.

FIGURE 1 mm of rain (horizontal axis) and umbrella sales (vertical axis)

Oct 2018 | AMSj Vol. 13

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15 TRIAL AND ERROR

Trial before and after error M. Ali and R.J. Molenaar

The first clinical rotation for most medical students is Internal Medicine. For many, this rotation is all about hearing and seeing mysterious and sometimes incomprehensible illnesses and critically ill patients. Some cases are complete mysteries for medical students, including those who used to be the best in their class or even their year. These cases often completely shattered my confidence and made me doubt whether I knew anything at all.

the outpatient clinic. This time a pneumonia was diagnosed. More importantly, the actual reason for the blood count was explained: an aggressive type of lymphoma. My skepticism had not been unfounded. Any medical student and any doctor should always keep asking the same question that any four-year-old does: “Why? Why was this done the way it was?”. I was amazed.

This seemingly enormous gap in knowledge between my supervisors and me, that I became so aware of in only a few weeks, caused me to stop asking questions about findings that I thought were unexpected, because everything else was often just that: unexpected.

And yet one case was different. At first I was still full of hesitation to ask questions when this patient with dyspnea and anemia was admitted. The resident diagnosed a dietary deficiency, which was in line with some of the lab results. But, when I further inspected the lab results, I saw increased reticulocytes, which seemed contradictory to this diagnosis.

However, even then I knew that the causes of anemia were so extensive that entire hematology books were written on this topic. I was therefore unsure whether my skepticism (‘’my gut’’) was anything to rely on. After all, I had only a month of clinical experience, so what were these guts based on anyway.

With my last courage (and skepticism) I decided to discuss this matter with my supervisor since the values still seemed a little out of place. To my pleasant surprise my concerns were listened to, discussed and even, partially acknowledged. The plan was to ask the patient to report back to the outpatient clinic to see if the diet had had any effects. I was satisfied.

And then the patient returned, but sooner than expected and to the emergency department instead of AMSj Vol. 13 | Oct 2018

16 CHANGING PERSPECTIVES

Depression – opposing ancient tradition D.G. Simons and P. de Koning

Depression, formerly known as melancholia, has long had its biological roots in classical antiquity since Hippocrates’ humorism attributed depression to an excess of black bile.1 The earliest Hippocratic writings emphasize the importance of context in differentiating ordinary sadness from melancholia.

Hippocrates’ theories remained relatively unaltered until the seventeenth century, two millennia after the conception of humorism, when empirical tradition arose. This sparked new perceptions on many facets of science, including psychology. Instead of humoral imbalance, disturbances of the brain and the nervous system started to become recognized as the root of depressive disorders.2

REFERENCES

1.

2.

3.

4.

Widmer DAJ. Black Bile and Psychomotor Retardation: Shades of Melancholia in Dante’s Inferno. Journal of the History of the Neurosciences. 2004;13(1):91-101.

V Horwitz A, C Wakefield J, Lorenzo-Luaces L. History of Depression. 2016.

Horwitz AV. How an Age of Anxiety Became an Age of Depression. The Milbank Quarterly. 2010;88(1):112-138.

Antidepressant Use in Persons Aged 12 and Over: United States, 2005–2008. https://www.cdc.gov/nchs/data/ databriefs/db76.htm. Accessed 18-09-2018.

Simultaneously, melancholic feelings were dichotomized into relatively mild and often somatic “sub-melancholic” symptoms, treated by general physicians. The more severely ill melancholic patients, having symptoms of suicidality, anguish and hopelessness, were assumed to have mental diseases and were treated by specialized healers in asylums. This dichotomy lasted into the twentieth century and the somatic symptoms were often emphasized as ‘neurotic problems’ or ‘stress’. Subsequently, depression was rarely diagnosed as general physicians tended to use the terms ‘anxiety’ and ‘stress’ to encapsulate most sub-melancholic mental health problems.2 It was not until the introduction of the DSM-III in 1980 that the traditional distinction between melancholic and neurotic depression was lifted.

In addition, pharmaceutical companies linking symptoms of anxiety to melancholic depression, shifted their marketing towards a wider audience consisting of both depressed and sub-melancholic patients. As a result, depression diagnoses skyrocketed and antidepressant sales have risen to become one of the most used medications in persons aged 18-44. Consequently, the long-established line separating sub-melancholic from melancholic depressed patients were blurred.3,4

Oct 2018 | AMSj Vol. 13

17 EXPERT OPINION

Thirty minutes of exercise a day keeps the doctor away?

N. M. Rosenberg and N. Rol

Shibata S, Fujimoto N, Hastings JL, Carrick-Ranson G, Bhella PS, Hearon CM, Jr., et al. The effect of lifelong exercise frequency on arterial stiffness. The Journal of Physiology. 2018;596(14):278395.

BACKGROUND

Lifestyle interventions like regular exercise are becoming more important in preventing cardiovascular disease worldwide. According to the World Health Organization (WHO), physical inactivity is the fourth leading risk factor for global mortality; 150 minutes of moderate-intensity exercise or 75 minutes of vigorous-intensity exercise a week is recommended.1 This amount of exercise prevents cardiac atrophy and arterial stiffening as a result of sedentary aging;2 however, the effects of a less frequent dose of exercise on arterial stiffening, as a marker of cardiovascular health, are unclear. This article investigated the association between different doses of exercise and arterial stiffness.

ABSTRACT

Central arterial stiffness increases with sedentary ageing. While near-daily, vigorous lifelong (>25 years) endurance exercise training prevents arterial stiffening with ageing, this rigorous routine of exercise training over a lifetime is impractical for most individuals. The aim was to examine whether a less frequent ‘dose’ of lifelong exercise training (four to five sessions per week for > 30 min) that is consistent with current physical activity recommendations elicits similar benefits on central arterial stiffening with ageing. A cross-sectional examination of 102 seniors (>60 years old) who had a consistent lifelong exercise history was performed.

Subjects were stratified into four groups based on exercise frequency as an index of exercise ‘dose’: sedentary: fewer than two sessions per week; casual exercisers: two to three sessions per week; committed exercisers: four to five sessions per week; and Masters athletes: six to seven sessions per week plus regular competitions. Detailed measurements of arterial stiffness and left ventricular afterload were collected. Biological aortic age and

central pulse wave velocity were younger in committed exercisers and Masters athletes compared to sedentary seniors. Total arterial compliance index (TACi) was lower, while carotid β-stiffness index and effective arterial elastance were higher in sedentary seniors compared to the other groups.

There appeared to be a dose–response threshold for carotid β -stiffness index and TACi. Peripheral arterial stiffness was not significantly different among the groups. These data suggest that four to five weekly exercise sessions over a lifetime is associated with reduced central arterial stiffness in the elderly. A less frequent dose of lifelong exercise (two to three sessions per week) is associated with decreased ventricular afterload and peripheral resistance, while peripheral arterial stiffness is unaffected by any dose of exercise.

REVIEW

This retrospective cohort study addresses an important topic in the expanding elderly population.

Participants were included if they consistently reported the same level of exercise for over 20 years. This contributes to reliable data concerning exercise as a preventive strategy. The four groups made it possible to compare Masters athletes to sedentary subjects as well as casual and committed exercisers. Next to these strengths, there are also some limitations in this study. Subjects were included if they were healthy, with a Body Mass Index (BMI) below 30 kg/m2, non-smoking and without cardiovascular disease. Also, it is likely that the participants had healthy lifestyle, leading to possible confounders like alcohol intake and nutrition. Therefore, the results of this study are not representative for the general population. Another problem is the reliance on self-reported questionnaires.

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18 CLINICAL IMAGE

CONCLUSION

The results of this study contribute to the preventive strategies for a healthier elderly population. A low frequency in exercise seems to have a positive effect on cardiovascular health, but further research has to tell whether these results are applicable to the general population. To be on the safe side, keep exercising 150 minutes per week.

A periocular rash B. de Jong, L. A. A. Gerbens and S. Darma

REFERENCES

1.

2.

World Health Organization. Global Strategy on Diet, Physical Activity and Health. 2018.

Bhella PS, Hastings JL, Fujimoto N, Shibata S, Carrick-Ranson G, Palmer MD, et al. Impact of lifelong exercise â&#x20AC;&#x153;doseâ&#x20AC;? on left ventricular compliance and distensibility. Journal of the American College of Cardiology. 2014;64(12):1257-66.

CASE

A 60-year old male patient presented with a diffuse bilateral periocular non-pruritic erythema since one year. No papules or flaking were present and the erythema did not respond to sunlight exposure. The patient also noted continuous weakness in both upper arms and increased fatigue. Previous medical history was insignificant and no atopy, known allergy, or medication use was present. There were no other skin symptoms. Visual acuity was 20/20 in both eyes (having 20/20 vision means that your visual acuity at 20 feet away from an object is equal to that of eyes of an average healthy individual). Intra-ocular pressure, ocular motility, color vision, slit lamp examination including the external eye and fundoscopy were unremarkable.

No ptosis was present. After consultation with the dermatologist a punch biopsy of the eyelid was performed.

QUESTION

What is the most likely diagnosis?

A. Allergic or Contact Dermatitis B. Blepharitis C. Myasthenia Gravis D. Dermatomyositis E. Systemic Lupus Erythematosus

?

Answer on page 21 Oct 2018 | AMSj Vol. 13

19 RADIOLOGY IMAGE

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20 RADIOLOGY IMAGE

Answers

cases. Secondary causes of sclerosing cholangitis should be ruled out.

T.L. Kortlever and K. de Wit

Therapeutic options in PSC are very limited: in general, ursodeoxycholic acid is used in PSC patients â&#x20AC;&#x201C; although its efficacy is the subject of intense debate. Trials are being conducted to identify possible other therapeutic targets. Ultimately up to 40% of patients will receive a liver transplantation.3

Correct answers: 1C, 2C, 3A. The MRCP images of this case reveal a significant sign: the intrahepatic bile ducts appear irregular, with strictures and dilatations somewhat similar to a string of beaded jewellery. This pattern is the hallmark of Primary Sclerosing Cholangitis (PSC).1 PSC is a rare idiopathic disease that causes stricturing and fibrosis of the intra- and/or extrahepatic bile ducts, resulting in bile flow and formation irregularities and progressive liver dysfunction.2-4 PSC has a prevalence of 16.2 per 100.000 and is unequally distributed among the sexes (male to female ratio 2:1. The pathogenesis of PSC is believed to be multifactorial, with genetic, environmental and immune factors identified as potential causes. Up to 80% of patients with PSC also have (or develop) Inflammatory Bowel Disease (IBD).

Arguably like IBD, studies have suggested that PSC is an heterogeneous disease, encompassing multiple subtypes that are yet to be identified. In addition, PSC is associated with a higher risk of malignancies, such as cholangiocarcinoma (1020%) and, in patients with both PSC and IBD, colorectal cancer.2 On the other hand, 5-10% of all patients with colitis have signs of PSC or will develop PSC.2 Approximately half of all patients do not experience any symptoms at first presentation. Those who do, present mainly with pruritus, pain in the right upper abdominal quadrant and fatigue. Patients have a cholestatic liver biochemistry in their lab results. MRCP imaging is primarily used to diagnose PSC, as this technique allows for a detailed cholangiographic assessment of the biliary tree.

ERCP may be used for diagnostics in some cases (e.g. when a well performed MRCP is inconclusive), but is mainly used for intervention purposes.

However, ERCP has a higher risk of complications, namely pancreatitis and cholangitis. Other diagnostic tools, such as a liver biopsy or assessment of auto-antibodies, are of little value in most

FIGURE 2 Image taken from an ERCP, case courtesy of Dr Hani Salam, Radiopaedia.org, rID: 14769

REFERENCES

1.

2.

3.

4.

Gaillard F. Primary sclerosing cholangitis, Radiology Reference Article, Radiopaedia.org. Radiopaedia.org. https://radiopaedia.org/articles/primary-sclerosing-cholangitis. Published 2018. Accessed August 12, 2018.

Dyson J, Beuers U, Jones D, Lohse A, Hudson M. Primary sclerosing cholangitis. The Lancet.

2018;391(10139):2547-2559. doi:10.1016/s01406736(18)30300-3 Lazaridis K, LaRusso N. Primary Sclerosing Cholangitis.

New England Journal of Medicine. 2016;375(12):11611170. doi:10.1056/nejmra1506330 Boonstra K, Ponsioen CIJ, Rauws EAJ, Beuers U. Primaire scleroserende cholangitis. Ned Tijdschr Geneeskd.

2010;154:A1476

Oct 2018 | AMSj Vol. 13

21 CLINICAL IMAGE

Answers B. de Jong, L. A. A. Gerbens and S. Darma

Correct answer: D

EXPLANATION

A.

Allergic or contact dermatitis. This is not the correct answer. Periocular dermatitis, or often dermatoconjunctivitis is most commonly caused from a type 4 hypersensitivity reaction (allergic) or irritant cause (contact) such as from cosmetic products. Often it is the first site where contact dermatitis is seen. It presents with hyperemia of the eyelids as observed in this patient, however it is usually pruritic and can cause swelling of the eyelids. More importantly it does not explain the other symptoms of this patient.

B. Blepharitis. This is not the correct answer.

Skin conditions such as rosacea and seborrheic dermatitis are associated with types of blepharitis, however these conditions typically spare the periocular area. Blepharitis can involve the periocular area, but the unremarkable external eye examination of this patient did not show signs of blepharitis such as eyelid inflammation, flaking, and/or meibomian gland dysfunction.

C. Myasthenia gravis. This is not the correct answer. This patient presents with muscle weakness, however it is continuous in character whereas myasthenia gravis typically presents with periodic ocular motility disorders, muscle weakness and ptosis increasingly during the day and after repeated movements. Systemic myasthenia gravis affects the voluntary muscles including the ocular muscles. Ocular myasthenia gravis only affects the ocular muscles. There is no association with erythematous rashes.

D. Dermatomyositis. This is the correct answer. The punch biopsy of the eyelid showed unspecified inflammation. Laboratory tests showed elevated serum creatine kinase without presence of anti-nuclear antibodies. Dermatomyositis was highly suspected in this patient and a muscle biopsy of the thigh was performed. The biopsy showed perivascular inflammation of the endomysial and

perimysial capillaries confirming the diagnosis.

The erythema in this patient is the typical heliotrope form found in this disease. Proximal bilateral muscle weakness and fatigue are common symptoms. No other clinical signs such as Gottronâ&#x20AC;&#x2122;s papules, shawl sign, mechanic hands, or periungal telangiectasias were present in this patient. As there is an association between dermatomyositis and malignancy (most commonly lung, stomach, ovary, and breast) imaging was ordered; no malignancy was found. Symptoms improved following treatment with high-dose oral prednisone. Follow-up visits over the next 3 years did not show malignancies. Tapering prednisone and switching to steroid-sparing medication over this period proved difficult with repeated disease flares. As such the patient is still using 5 mg prednisone daily in combination with azathioprine.

E. Systemic lupus erythematosus. This is not the correct answer. The heliotrope rash in this patient can be mimicked by systemic lupus erythematosus (SLE), while a photosensitive malar rash sparing the eyelids is more common. Myositis is also one of many possible symptoms of this disease, however the combined presence of the heliotrope rash and proximal muscle weakness make dermatomyositis highly suspected. This patient would also only qualify for at most 2 out of 4 needed criteria according to the diagnostic ARA classification for SLE. Differentiating between SLE and dermatomyositis can be difficult in certain patients as biopsy results can be similar. However, anti-nuclear antibodies are less commonly found in dermatomyositis and include subtype anti-Jo-1 instead of anti-Smith and anti-dsDNA subtypes found in SLE.

REFERENCE

1.

Dugan, E. M., Huber, A. M., Miller, F. W., & Rider, L. G. (2009). Photoessay of the cutaneous manifestations of the idiopathic inflammatory myopathies. Dermatology online journal, 15(2).

AMSj Vol. 13 | Oct 2018

22 ARTICLE

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EDITORS IN CHIEF A.V. de Jonge, M.A. Kempeneers, G.E. Linthorst, F. Daams BOARD S. Veldkamp, W.D. Krishnasing, I. de Brouwer, O. Moussa, J.M. Tettero, E.M. van Praag CONTENT EDITOR & NATIVE EDITOR T.R. de Back, M.E. Ribbink STAFF REVIEWERS S. Bossers, N.H. Sperna Weiland, G. de Waard, K.G.J.A. Voogdt, F. de Leeuw, E.P. van Poelgeest, J. Stiekema, J. Cloos, A. Emanuel, J. ten Kulve, L. Vogt, M.W. Bijlsma, N. Rol, M.C. Brouwer, J.W. Wilmink, R.J. Molenaar, S. Darma, M.U. Schafroth, P.P. de Koning, M. Maas, R. van Bentum, K. de Wit, L.A. Gerbens, B. Lissenberg-Witte, S.W. de Jonge STUDENT REVIEWERS S. Rozemeijer, L.S.F. Konijnenberg, K. Ergin, M. Haverkort, K. Engelfriet, B.J. Verhaar, J.M. Tettero, J. Saris, E.M. Corazolla, R.K. Feenstra, R.A.L. Beekman, N.M. Rosenberg, E. Neefjes, M. Ali, B. de Jong, D.D.G. Simons, M. Kocyigit, T.L. Kortlever, M.M Wennekers

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