BMC Neurology - Latest Comments

Medication Overuse Headache (MOH) definition

Ibrahima Soumaoro — 2013-03-10T13:28:54Z

According to SD Silberstein et al. Cephalalgia 2005; 25:460¿465 (Revision-of-criteria-8.2-MOH) and ICDH-IIR, the diagnosis criteria for MOH are the following:

A Headache present on ¿ 15 days/month fulfilling criteria C and D.
B Regular overuse for > 3 months of one or more drugs that can be taken for acute and/or symptomatic treatment of headache.
C Headache has developed or markedly worsened during medication overuse.
D Headache resolves or reverts to its previous pattern within 2 months after discontinuation of overused medication.

Overuse is defined in terms of duration and treatment days per week. What is crucial is that treatment occurs both frequently and regularly, i.e. on 2 or more days each week. Bunching of treatment days with long periods without medication intake, practiced by some patients, is much less likely to cause medication-overuse headache and does not fulfill criterion B.

I'm concerned that majority of your sample might not fulfill the above definition criteria of MOH, especially in regard to the duration and treatment days per week (frequency and regularity of overuse).
I'm not sure if those subjects that were not frequent and not regular over users can be diagnosed as MOH. For example taking the medication only during the first 11 days of the month, or 5 days in the first week of the month and 6 days in the fourth week etc...
I will appreciate if you could provide me with explanation on how you controlled this in your sample and analysis?

Consideration in future researches

Mehdi Farhoudi — 2013-03-10T13:19:01Z

Dear Dr. Soleimanpour,

Congratulations to you and your colleagues for publishing this innovative research paper in this professional journal. The article is great and I think all related limitations were mentioned. It seems that in this phase propofol should be used in emergency departments with monitoring facility and it is better to propose other study with solving of the limitations and considering cost-benefit issues.

Best Regards,
Mehdi Farhoudi
Prof. of Neurology

Comment on BMC Neurol 2012 12: 6

Ulrik Dalgas — 2012-06-18T10:39:02Z

Dalgas U, Kjoelhede T,
Department of Public Health, Section of Sport Science, Aarhus University, Denmark

de Groot V,
Department of Rehabilitation Medicine, VU University Medical Center, Amsterdam, The Netherlands

Eijnde BO and Feys P
BIOMED, Hasselt University, Diepenbeek and REVAL Research Institute, PHL University College, Hasselt, Belgium

In a recent paper in this journal Motl et al.[1] question a recent recommendation of replacing the 6 minute walk test (6MWT) with the 2 minute walk test (2MWT) when assessing walking performance in clinical trials evaluating patients with multiple sclerosis (MS)[2]. In the paper the presented argument for maintaining the 6MWT as an outcome measure in clinical trials is based on the difference in the physiological demand (i.e. oxygen consumption and metabolic processes) between the two tests.
Motl et al. showed a curvilinear increase in VO2 during the first three minutes of the test, followed by a plateau (`steady-state¿) during the last three minutes. Based on this finding the authors state, that in the first part (equal to the 2MWT) of the 6MWT energy is produced by a combination of anaerobic and aerobic metabolism, whereas in the last part of the 6MWT energy is produced by aerobic metabolism. The authors conclude that the 2MWT and 6MWT measure different metabolic features of walking and have different interpretations as clinical outcome variables.
However, in order to investigate the actual contribution of different energy systems, Motl et al. should have provided additional information regarding the relative intensity of the test by performing a maximal oxygen uptake test (or an estimation of VO2max) and also by reporting values of the respiratory exchange ratio (RER). The RER value must have been obtained given that CO2-secretion was measured simultaneously with O2-uptake by the K4b2 mobile equipment (Cosmed, Italy). This would likely have shown that the test is performed at a moderate intensity (approximately 69% of maximal heart rate), as is shown in other studies[3].
Although there might be a slight difference in metabolic demand between the first and the last minutes of the 6MWT, we argue that, neither the aerobic nor the anaerobic energy system is functioning near its maximal capacity, because multiple studies have indicated that the test is very likely performed at sub-maximal intensities [3-5]. This means, that walking performance in neither of the two tests is limited by the metabolic systems providing energy. Therefore, we question the suitability of the 6MWT to test the function of these metabolic systems, and, consequently, the conclusion of Motl et al. that the 6MWT adds significant information in addition to the 2MWT.
However, we would agree that other arguments can be presented in the debate of choice of walking test. Comprehensive norm-data already exist for the 6MWT, while those of the 2MWT first need to be collected, what can easily be done if the 2MWT earns consensus. Another argument may relate to the responsiveness of the 2MWT compared to the 6MWT, which at present is unknown.
The purpose of applying the 2MWT and the 6MWT in clinical trials is to monitor degree of walking disability in a clinical setting, and not to monitor sub-maximal energy metabolism. Because the 6MWT performance can be precisely predicted by the 2MWT performance[2; 6], while both are similarly related to habitual walking performance in MS patients[7], we still think that it is justified to conclude, that the 2MWT can replace the 6MWT in clinical practice, when measuring walking disability in persons with MS.

References

1. Motl, RW, Suh, Y, Balantrapu, S, Sandroff, BM, Sosnoff, JJ, Pula, J et al. Evidence for the different physiological significance of the 6- and 2-minute walk tests in multiple sclerosis. BMC Neurol 2012 12: 6.
2. Gijbels, D, Dalgas, U, Romberg, A, de, G, V, Bethoux, F, Vaney, C et al. Which walking capacity tests to use in multiple sclerosis? A multicentre study providing the basis for a core set. Mult Scler 2011
3. Chetta, A, Rampello, A, Marangio, E, Merlini, S, Dazzi, F, Aiello, M et al. Cardiorespiratory response to walk in multiple sclerosis patients. Respir Med 2004 98: 522-529.
4. Bosnak-Guclu, M, Gunduz, AG, Nazliel, B, Irkec, C. Comparison of functional exercise capacity, pulmonary function and respiratory muscle strength in patients with multiple sclerosis with different disability levels and healthy controls. J Rehabil Med 2012 44: 80-86.
5. Paltamaa, J, Sarasoja, T, Leskinen, E, Wikstrom, J, Malkia, E. Measuring deterioration in international classification of functioning domains of people with multiple sclerosis who are ambulatory. Phys Ther 2008 88: 176-190.
6. Gijbels, D, Eijnde, BO, Feys, P. Comparison of the 2- and 6-minute walk test in multiple sclerosis. Mult Scler 2011 17: 1269-1272.
7. Gijbels, D, Alders, G, Van, HE, Charlier, C, Roelants, M, Broekmans, T et al. Predicting habitual walking performance in multiple sclerosis: relevance of capacity and self-report measures. Mult Scler 2010 16: 618-626.

concern regarding a review published by Plested et al. 2010 on various medications for refractory neuropathic pain

Detlef von Zabern — 2012-06-08T13:28:37Z

1. Definition of refractory neuropathic pain (NeP)
The authors state in their inclusion/exclusion criteria that `Owing to the lack of a consensus definition of refractory NeP, this review took a pragmatic approach to define refractory NeP broadly as patients who had failed to receive adequate pain relief from or were intolerant to previous therapy irrespective of the duration, dose and type of previous therapy¿. According to common understanding, this should encompass all patients with partial, incomplete or no response to previous neuropathic pain therapy. Thus, while the definition is very broad and may require rewording, it may well serve for practical purposes but should as a result apply to a broader range of publications than analysed in this manuscript. Indeed, when following the December 2008 cut-off point chosen by the authors, a search of duloxetine and lidocaine publications found lidocaine plaster studies such as White et al. 2003 [1 `Patients with postherpetic neuralgia, painful diabetic neuropathy, or low back pain with partial responses (average daily pain intensity >4/10) to their current analgesic treatment regimen were included¿] and Argoff et al. 2004 [2 `Patients with PHN, painful DN, and LBP were enrolled if they had partial response to gabapentin-containing analgesic regimens and if they reported moderate-to-severe pain on the NPS at study enrolment¿] which should have been included.
In addition, criteria for studies included in this review appear to differ throughout the paper thus inclusion criterion for the pregabalin study by Obermann et al. 2008 [3] was ¿All but three of patients had received prior therapy, therefore may be considered refractory¿. According to the reported mean baseline pain intensity score and pain duration, the majority of patients in this study were likely refractory however, this is pure speculation, not stated in the paper and may or may not apply to almost any other study in which patients received prior medication. If the inclusion criteria used to include the study by Obermann et al. are used (and we are not suggesting they should), then they should also have been applied e.g. to include the study by Meier et al. [4] and - with a more up-to-date literature research (see point 2 below) - also the studies by Hans et al. 2009 [5] and Baron et al. 2009 [6].

2. Literature search cut-off point
By the time the review was available online (Nov 2010), the literature search data with a cut-off point of Dec 2008 were nearly two years old. The authors included two 2009 pregabalin references in their discussion but did not extend this update to new lidocaine plaster publications such as Fleming and O¿Connor 2009 [7], Wilhelm et al. Feb 2010 [8], and Baron et al. Jul 2009 [6]. Considering the authors¿ mention of the lack of head-to-head trials in the review discussion, we do not understand why the latter study in particular was not included prior to publication of the review. The study by Baron et al. [6] describes a randomised trial in patients with PHN or DPN. Patients received either pregabalin or lidocaine plaster as monotherapy for 4 weeks (55.5% patients were sufficiently treated with lidocaine plaster monotherapy and 56.4% were sufficiently treated with pregabalin monotherapy). For the following 8 weeks, sufficiently treated patients continued monotherapy and if treatment had been insufficient during the first 4 weeks (=refractory) patients received the other treatment as an add-on for 8 weeks. Improvements were comparable in both add-on groups. Although this study does not completely meet the inclusion criteria set for the review since both drugs were administered together to these refractory patients, we, however, feel that this study provides important information concerning successful treatment of refractory patients with both drugs and should not have been omitted in the discussion of the review.

3. Inclusion of pregabalin study reference 34 (Sommer et al. 2007)
The study by Sommer and colleagues [9] investigated the use of pregabalin in the treatment of (mostly secondary) RLS. Only seven of the 19 RLS patients suffered from neuropathic pain. Sixteen patients had been previously treated with dopaminergic medication (for their RLS) and were refractory to their previous RLS medication. Eight patients received gabapentin and four patients opioids as previous treatment (from the wording we assume that this medication was also for the treatment of RLS symptoms). This study clearly does not investigate pregabalin for the treatment of neuropathic pain but for the treatment of RLS. In fact the authors scored relief from core RLS symptoms only (i.e. relief from neuropathic pain is not reported) and they tried to distinguish between the two by asking the patients to score the RLS symptoms with a diurnal rhythm rather than permanent symptoms. This very interesting study pointing to a relationship between neuropathy and RLS clearly does not refer to refractory neuropathic pain and should therefore not have been included in the review. Furthermore, inclusion of this study indicates the lack of thoroughness by which the search was conducted and highlights the biased and random inclusion of citations used.

4. Availability of cited references
Unfortunately, not all review references are available for perusal. Despite an extensive search, we were unable to locate review ref. 41 (abstract by Douglas et al. 2008). The full paper given as a link to this reference (ref. 31, Douglas et al. 2006) could also not be found with the provided citation.

Although our research did not find any pre- or post-2008 duloxetine studies which fit the inclusion criteria, several lidocaine plaster studies did. Exclusion of these studies and exclusion of duloxetine studies (apparently because prior therapies were not reported) misguides the reader into believing that pregabalin is the only effective treatment in the context of refractory neuropathic pain. Differences in safety profiles of the included medications is given very little consideration and the discussion is almost entirely focussed on pointing out benefits of pregabalin. All this can surely not be the purpose of a comparative review and is certainly not going to be for the best benefit of the patients concerned.

References
1. White WT, Patel N, Drass M, Nalamachu S. Lidocaine patch 5% with systemic analgesics such as gabapentin: a rational polypharmacy approach for the treatment of chronic pain. Pain Med 2003 Dec, 4(4): 321-330.
2. Argoff CE, Galer BS, Jensen MP, Oleka N, Gammaitoni AR. Effectiveness of the lidocaine patch 5% on pain qualities in three chronic pain states: assessment with the Neuropathic Pain Scale. Curr Med Res Opin 2004, 20 Suppl 2: S21-28.
3. Obermann M, Yoon MS, Sensen K, Maschke M, Diener HC, Katsarava Z. Efficacy of pregabalin in the treatment of trigeminal neuralgia. Cephalalgia 2008, 28: 174-181.
4. Meier T, Wasner G, Faust M, Kuntzer T, Ochsner F, Hueppe M, Bogousslavsky J, Baron R. Efficacy of lidocaine patch 5% in the treatment of focal peripheral neuropathic pain syndromes: a randomized, double-blind, placebo-controlled study. Pain 2003 Nov, 106(1-2): 151-158.
5. Hans G, Joukes E, Verhulst J, Vercauteren M. Management of neuropathic pain after surgical and non-surgical trauma with lidocaine 5% patches: study of 40 consecutive cases. Curr Med Res Opin 2009, 25(11): 2737-2743.
6. Baron R, Mayoral V, Leijon G, Binder A, Steigerwald I, Serpell M. Efficacy and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin in post-herpetic neuralgia and diabetic polyneuropathy. Curr Med Res Opin 2009 Jul, 25(7): 1677-1687.
7. Fleming JA, O'Connor BD. Use of lidocaine patches for neuropathic pain in a comprehensive cancer centre. Pain Res Manag 2009 Sep-Oct, 14(5): 381-388.
8. Wilhelm IR, Tzabazis A, Likar R, Sittl R, Griessinger N. Long-term treatment of neuropathic pain with a 5% lidocaine medicated plaster. Eur J Anaesthesiol 2010 Feb, 27(2): 169-173.

Errata for Coulthart et al., BMC Neurology 2011 Oct 27;11(1):133

Michael Coulthart — 2011-11-26T16:41:47Z

There are two typographical errors in the final published version of this paper, for which the corresponding author accepts full responsibility. Page references are to the final PDF version.

1. Page 6, first paragraph, line 7:

" ... result below T2.5 + T1000 ... " should read
" ... result below T2.5 + T976 ... ".

2. Table 3, lines 4 and 10:

"T1000" should read "T976".

M.B. Coulthart

Including insomniac/sleep deprevation patients in future studies?

John Mitchell jr — 2011-07-08T17:23:19Z

One of the most distressing facets of CFS is the disrupted/interrupted sleep patterns experienced by many patients, which have a profound impact on quality of life. As a longtime CFS patient disrupted sleep was one of my first symptoms of illness, long before I became disabled due to cognitive dysfunction, weakness and post-exertional malaise, with the main problem being that I wake up from sleeping after a couple hours and then constantly awaken and try to go back to sleep for the rest of the night, every night. This has went on for the past decade, leaving me severely sleep deprived, and seems to fit with the reduced stage 4 sleep and alpha wave intrusion reported in several CFS sleep studies.

Although I am not educated on the techniques involved in this study, it would seem that variables such as insomnia and/or sleep deprivation would plausibly affect brain function in a manner distinct from depression and would possibly make for good comparison groups in future studies.

Thank you very much to the authors for your work on this disease.

Correction available

Otmar Bayer — 2011-06-20T16:07:45Z

A correction to our article is available at http://www.biomedcentral.com/1471-2377/11/45.

Typographic errors in Manuscript

Maia Beridze — 2011-05-31T14:33:40Z

There are several typographic errors in manuscript final version that are important to mention as they can distort the scientific essence of paper.

In Table 2- After: Data represents means (SD) should be indication * P<0.05.

In the legend of Figure 1
After: P < 0.05 between the Group 1, Group 2 and control
Should be : P < 0.50 between the Group 1 and Group 2

In the legend of Figure 2
Instead of :
P < 0.50 between the Group 1 and Group 2
Should be:
P < 0.05 between the Group 1 and Group 2

This is also obvious while looking at the figures.

Author of this comments: Maia Beridze MD.PhD. The first author of presented manuscript.

corrections

illora darbar — 2011-05-31T14:30:41Z

On Table 2, last column: The correct is p>0.999, not p=0.999. The correct is p=0.153, not p=1.53.

No association between celiac disease and multiple sclerosis in population-based data

Jonas Ludvigsson — 2011-05-31T14:06:10Z

The authors are to be commended for their interesting study. At the same time I would like to draw their attention to the largest study on celiac disease and mutliple sclerosis to this date:
Ludvigsson JF, Olsson T, Ekbom A, Montgomery SM. A population-based study of coeliac disease, neurodegenerative and neuroinflammatory diseases. Aliment Pharmacol Ther 2007;25(11):1317-27.

http://www.ncbi.nlm.nih.gov/pubmed/17509100?dopt=Citation

In this study we examined the risk of multiple sclerosis (and other neurological disorders) in 14,000 patients with celiac disease in Sweden. Patients with celiac disease were at no increased risk of MS (Hazard ratio, HR=0.9; 95%CI=0.3-2.3).

When in a case-control analysis we instead investigated the risk of a future celiac disease diagnosis among individuals who were first diagnosed with MS, the Odds ratio for future CD was 1.8 (95%CI=0.9–3.7).

I would be interested to hear from the authors why our study results differ?

Yours sincerely, Dr Jonas F Ludvigsson