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Investigation of the Association between Headache Type, Frequency, and Clinical and Radiological Findings in Patients with Multiple Sclerosis
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.304126
Keywords: EDSS, headache, MRI, multiple sclerosis
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.
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.
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].
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].
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].
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].
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].
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.
[Figure 1]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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