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ORIGINAL ARTICLE
Year : 2020  |  Volume : 68  |  Issue : 6  |  Page : 1333-1337

Investigation of the Association between Headache Type, Frequency, and Clinical and Radiological Findings in Patients with Multiple Sclerosis


1 Neurology Clinic, Hatay State Hospital, Antakya, Hatay, Turkey
2 Neurology Department, Medicine Faculty, Hatay Mustafa Kemal University, Hatay, Turkey

Date of Web Publication19-Dec-2020

Correspondence Address:
Dr. Murat Guntel
Neurology Department, Medicine Faculty, Hatay Mustafa Kemal University, Hatay, Turkey Zip code: 31000
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.304126

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 » Abstract 


Aim: In this study, we aimed to investigate the prevalence of primary headaches in patients with multiple sclerosis (MS), to determine the type of headache according to the criteria of International Headache Society and to investigate the relationship between primary headache type and MS subtype, and the relationship between the localization of plaques in the brain magnetic resonance imaging (MRI) with MS clinic.
Methods: In this study, we include the patients diagnosed with MS according to the Mc Donald criteria and functional loss determined with Expanded Disability Status Scale (EDSS). We include the patients who were questioned about headache characteristics in detail and the patients who have MRI previously. MRI evaluations of plaque localization of the patients were classified retrospectively.
Findings: Headache in 54.4% of 320 patients participated in the study are available (23.8% tension-type headache (TTH), 30.6% migraine). When we look at the first three initial symptoms of MS patients, the patients who have polysymptomatic symptoms at the beginning are 25.3%, those with motor symptoms are 23.1%, and patients with optical symptoms are 19.7%. The mean EDSS was 2.6 ± 1.9. When we look the lesion localization, at most pericallosal lesions are present. Mean disease duration was 9.9 years in patients with TTH and 4.5 years in patients with migraine. The difference was statistically significant (P < 0.05). The mean EDSS score was 4.7 in patients with TTH and 1.8 in patients with migraine, and the difference was statistically significant (P < 0.001). The average number of lesions in the brain was 22.07 in patients with TTH and 15.79 in patients with migraine. The difference was statistically significant (P < 0.001).
Results: In this study, the frequency of headache in MS patients was found to be greater than the general population and we found a higher incidence of migraine-type headache in these patients. We observed that the tension type of headache is more frequent in MS patients with higher ages, longer disease duration, more plaque numbers, and high EDSS scores.


Keywords: EDSS, headache, MRI, multiple sclerosis
Key Messages: Headache is quite common in MS patients. Determining the type of headache is very important for an effective treatment in these patients.
Many factors have been identified that affect MS prognosis. Among these factors, the initial symptoms of the patients, MRI lesion load and plaque localization are very important. Evaluation of these factors in predicting the clinical course is very beneficial for clinicians.


How to cite this article:
Demetgul O, Duman T, Guntel M. Investigation of the Association between Headache Type, Frequency, and Clinical and Radiological Findings in Patients with Multiple Sclerosis. Neurol India 2020;68:1333-7

How to cite this URL:
Demetgul O, Duman T, Guntel M. Investigation of the Association between Headache Type, Frequency, and Clinical and Radiological Findings in Patients with Multiple Sclerosis. Neurol India [serial online] 2020 [cited 2021 Jan 19];68:1333-7. Available from: https://www.neurologyindia.com/text.asp?2020/68/6/1333/304126




Multiple sclerosis (MS) is a chronic, probably autoimmune, demyelinating and degenerative disease of young adults affecting multiple regions in both white and gray matter of the central nervous system (CNS) with dissemination in space and time and characterized by exacerbations and remissions, and the disease is hypothesized to be caused by complex interactions of genetic and environmental factors[1],[2],[3]

This study aimed to investigate the association of primary headache with the clinical findings in MS subtypes and plaque locations on magnetic resonance imaging (MRI), based on the prevalence of primary headache in patients with MS and by defining the types of headache according to the criteria set by the International Headache Society.


 » Material and Methods Top


In this study, we include the patients diagnosed with MS according to the Mc Donald criteria and functional loss determined with Expanded Disability Status Scale (EDSS). We include the patients who were questioned about headache characteristics in detail and the patients who have MRI previously. MRI evaluations of plaque localization of the patients were classified retrospectively.

In total, 320 patients included in the study. These patients were questioned about headache characteristics consecutively to determine headache type. In total, 13 patients who were diagnosed with MS at admission but did not meet the Mc Donald criteria were excluded from the study. Six patients diagnosed with MS, but without registered MRI were excluded from the study. Thus, a total of 19 patients were excluded.

This study was planned to evaluate the association of primary headache with the clinical findings in MS and plaque locations on magnetic resonance imaging, based on the prevalence of primary headache in patients with MS and by defining the types of headache according to the criteria set by the International Headache Society.

Our study was approved by the Clinical Study Ethics Committee of Mustafa Keyal University Tayfur Ata Sökmen Medical Faculty (Approval no: 109, dated 06. 04. 2014).

Statistical analysis

Data were electronically recorded for analysis. Frequency tables, correlation analysis, Student's t-test, one-way ANOVA, and Chi-square test were used to analyze data.


 » Results Top


Of the 320 patients included in the study, 70.6% were female (n = 226) and 29.4% were male (n = 94). When the initial symptoms of MS patients were evaluated, the most symptomatic patients included polysymptomatic patients (25.3%), patients with motor symptoms (23.1%), and patients with optic symptoms (19.7%). Primary headache was present in 54.4% of the patients (migraine in 30.6%, tension-type headache (TTH) in 23.8%) [Table 1], [Figure 1].
Table 1: Gender and initial symptoms of the patients included in the study

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Figure 1: Prevalence and type of headache in MS patients

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The mean age of the subjects was 37.5 ± 10.8 years (range, 17–68 years). The mean EDSS score was 2.6 ± 1.9. The pericallosal region was the most common localization of the lesions (mean no. of lesions, 11.7 per patient). The mean total number of brain lesions was 17.2 ± 6.7 (range, 9–44) [Table 2].
Table 2: Age, EDSS scores, and number of MRI brain lesions of the patients included in the study

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The mean disease duration was 9.9 years in patients with TTH and 4.5 years in patients with migraine-type headache. The difference was statistically significant (P < 0.05).

There was a strong positive association between the disease durations and EDSS scores of MS patients, and this association was found to be statistically significant (P < 0.05, R = 0.550).

When the EDSS scores of the patients were evaluated in terms of initial symptoms, polysymptomatic patients and patients with motor symptoms had the highest scores (3.5).

A statistically significant difference was found between the initial symptoms and the mean EDSS scores (P < 0.001).

The mean EDSS scores in polysymptomatic patients and in patients with motor attack symptoms were higher than those in patients with optic, sensory, and cranial symptoms, and the difference was statistically significant (P < 0.05) [Table 3].
Table 3: Association between initial symptoms and EDSS scores in study patients

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The mean EDSS score was 4.7 in patients with TTH and 1.8 in patients with migraine-type headache. The difference was statistically significant (P < 0.001).

There was a strong positive association between the total number of brain lesions and EDSS scores in MS patients, and this association was statistically significant (P < 0.05, R = 0.679).

Of the patients with TTH, 96.1% had juxtacortical, 100% had pericallosal, 93.4% had infratentorial, and 64.5% had cerebellar lesions. Of the patients with migraine-type headache, 98% had juxtacortical, 100% had pericallosal, 78.6% had infratentorial, and 45.9% had cerebellar lesions [Table 4].
Table 4: Association between MRI lesion locations and primary headache types in study patients

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The mean total number of cerebral lesions was 22.07 in patients with TTH and 15.79 in patients with migraine-type headache. The difference was statistically significant (P < 0.001).

The mean total number of brain lesions was 18.53 in patients with headache and 15.77 in patients without headache. The difference was statistically significant (P < 0.001).

Migraine was more common in the patients with sensory, cranial, optic, or cerebellar symptoms at baseline, while TTH was more common in polysymptomatic patients and in the patients with motor symptoms at baseline [Table 5].
Table 5: Association between initial symptoms and headache types

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 » Discussion Top


MS is a disease of the CNS, characterized by inflammation, demyelination, and axonal loss. Its prevalence is 120/100,000, and its annual incidence is 7/100,000[4],[5]

The initial signs of MS are quite variable. There are no clinical signs specific to MS. Paty and Poser in their series of 461 patients found that 17% of the patients had optic neuritis, 13% had double vision, 36% had paresthesia and sensory impairment, 18% had balance and gait disorder, and 18% had motor weakness. However, it is reported that sensory and paroxysmal findings are more frequently found as initial findings due to keeping patient records regularly and easier access to these records during the recent years.[6]

Headache is not one of the general symptoms of MS. The first study about the association between MS and headache was published in 1969.[7] There are studies investigating the frequency of primary headache types in MS patients, and these studies reported that migraine and TTH were found in 24.6–70% and 24–48.2% of the patients, respectively.[8],[9],[10],[11] There is an unclear association between MS and headache. Many authors reported that there might be a possible connection between migraine-like headache and MS[12],[13]

This study investigated the association of primary headache with the clinical findings of MS and plaque locations on magnetic resonance imaging in patients with MS, based on the prevalence of primary headache in patients with MS and by defining the types of headache according to the criteria set by the International Headache Society.

In the London cohort, it was reported that 45% of the patients had sensory symptoms, 17% had optic neuritis, 20% had motor symptoms, 13% had diplopia/vertigo, and 13% had imbalance/extremity ataxia at baseline. In our study, when the baseline symptoms were evaluated, the most symptomatic patients included polysymptomatic patients (25.3%), patients with motor symptoms (23.1%), and patients with optic symptoms (19.7%). Optico-spinal presentation was observed in 37.6% (59/157) patients in other series.[14]

Related studies in the literature found that the lifetime prevalence of headache in MS patients was between 35.5 and 61.8%.[15],[16] In our study, primary headache was present in 54.4% of the patients. This rate was considered consistent with the other studies in the literature. This rate was statistically significantly higher than the rate reported for healthy population in the literature.

In different study groups, migraine and TTH were reported in 24.6–70% and 37.2–48.2% of the patients, respectively, and these rates were similar to those found in the control groups.[8],[9],[11]

In a study conducted in our country to investigate the frequency of headache in patients with MS, 36% of the MS patients had TTH and 25.2% had migraine. There was no difference during the pre-illness period and during the attack periods in our MS patients' group.[16]

In our study, like the rates in the literature, 30.6% of the MS patients had migraine while 23.8% had TTH. However, since our study was retrospective, the association between headache and MS could not be clearly evaluated.

Gee et al. reviewed the hospital records of 1533 patients with demyelination on MRI and included 277 patients with the diagnosis of MS in their study. In this study, the frequency of migraine, TTH, and migraine plus TTH were 4-fold, 2.5-fold, and 2.7-fold increased, respectively, in the patients with MS plaques close to the periaqueductal grey matter in the mesencephalon.[17] There are case reports in the literature highlighting the association between some lesion locations on MRI and headache. In our study, the mean total number of brain lesions was 18.53 in patients with headache and 15.77 in patients without headache. The difference was statistically significant, and the frequency of headache increased with increase in the total number of lesions. In addition, of the patients with TTH, 96.1% had juxtacortical, 100% had pericallosal, 93.4% had infratentorial, and 64.5% had cerebellar lesions. Of the patients with migraine-type headache, 98% had juxtacortical, 100% had pericallosal, 78.6% had infratentorial, and 45.9% had cerebellar lesions. Although the available data are insufficient for generalization, juxtacortical lesions were more frequent in patients with migraine than in patients with TTH, while infratentorial and cerebellar lesions were relatively more common in patients with TTH and all patients in both groups had pericallosal lesions.

In our study, the mean EDSS score was 4.7 in patients with TTH and 1.8 in patients with migraine-type headache. The difference was statistically significant (P < 0.001). Moreover, the mean disease duration was 9.9 years in patients with TTH and 4.5 years in patients with migraine-type headache. The difference was statistically significant (P < 0.05).

In addition, in our study, migraine was more frequent in the patients with sensory, cranial, optic, or cerebellar symptoms at baseline, while TTH was more common in polysymptomatic patients and in the patients with motor symptoms at baseline. Further studies are required since there are no studies in the literature reporting similar data on this rate.

Conclusion and Suggestions

In conclusion, we believe that there is a strong connection between MS and primary headache, but MS types other than relapsing remitting form were very few in the study. Therefore, which type of MS is related with headache could not be evaluated, so it was one of the limitations of the study. Further studies investigating the physiopathology and clinical and radiological features of this association in large groups of patients will be able to provide more definitive results.

Financial support and sponsorship

Funding: None.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Schumacher GA, Beebe G, Kıbler RF, Kurland LT, Kurtzke JF, Mcdowell F, et al., Problems of experımental trıals of therapy ın multıple sclerosıs: Report by the panel on the evaluatıon of experımental trıals of therapy ın multıple sclerosıs. Ann N Y Acad Sci 1965;122:552-68.  Back to cited text no. 1
    
2.
Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, et al. New diagnostic criteria for multiple sclerosis: Guidelines for research protocols. Ann Neurol 1983;13:227-31.  Back to cited text no. 2
    
3.
Singhal BS. Multiple sclerosis. Neurol India 1999;47:1-2.  Back to cited text no. 3
    
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Coles A. Multiple sclerosis. Pract Neurol 2009;9:118-26.  Back to cited text no. 4
    
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Singhal B. Multiple sclerosis-Indian perspective. Neurol India 2015;63:824-5.  Back to cited text no. 5
    
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Eraksoy M. MS Akademisi Türkiye. İstanbul: Turgut Yayıncılık; 2008. p. 19-26.  Back to cited text no. 6
    
7.
Headache in multiple sclerosis. Br Med J 1969;2:713-4.  Back to cited text no. 7
    
8.
Nicoletti A, Patti F, Lo Fermo S, Liberto A, Castiglione A, Laisa P, et al. Headache and multiple sclerosis: A population-based case-control study in Catania, Sicily. Cephalalgia 2008;28:1163-9.  Back to cited text no. 8
    
9.
Vacca G, Marano E, Brescia Morra V, Lanzillo R, De Vito M, Parente E, et al. Multiple sclerosis and headache co-morbidity. A case-control study. Neurol Sci 2007;28:133-5.  Back to cited text no. 9
    
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Freedman MS, Gray TA. Vascular headache: A presenting symptom of multiple sclerosis. Can J Neurol Sci 1989;16:63-6.  Back to cited text no. 10
    
11.
Putzki N, Pfriem A, Limmroth V, Yaldizli O, Tettenborn B, Diener HC, et al. Prevalence of migraine, tension-type headache and trigeminal neuralgia in multiple sclerosis. Eur J Neurol 2009;16:262-7.  Back to cited text no. 11
    
12.
Watkins SM, Espir M. Migraine and multiple sclerosis. J Neurol Neurosurg Psychiatry 1969;32:35-7.  Back to cited text no. 12
    
13.
Rolak LA, Brown S. Headaches and multiple sclerosis: A clinical study and review of the literature. J Neurol 1990;237:300-2.  Back to cited text no. 13
    
14.
Jena SS, Alexander M, Aaron S, Mathew V, Thomas MM, Patil AK, et al. Natural history of multiple sclerosis from the Indian perspective: Experience from a tertiary care hospital. Neurol India 2015;63:866-73.  Back to cited text no. 14
    
15.
Martinelli Boneschi F, Colombo B, Annovazzi P, Martinelli V, Bernasconi L, Solaro C, et al. Lifetime and actual prevalence of pain and headache in multiple sclerosis. Mult Scler 2008;14:514-21.  Back to cited text no. 15
    
16.
Sorgun M, Yücesan C. Headache in multiple sclerosis. Turk J Med Sci 2013;43:10429.  Back to cited text no. 16
    
17.
Gee JR, Chang J, Dublin AB, Vijayan N. The association of brainstem lesions with migraine-like headache: An imaging study of multiple sclerosis. Headache 2005;45:670-7.  Back to cited text no. 17
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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