Does ms cause headaches. Multiple Sclerosis and Headaches: Exploring the Connection in Early MS Diagnosis

16.10.197902.12.2021 by alexxlab

Does multiple sclerosis cause headaches. How prevalent are headaches in early MS. What types of headaches are common in MS patients. Can headaches be an early symptom of MS. How might headaches relate to MS pathophysiology.

Содержание

The Prevalence of Headaches in Early Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that can lead to significant disability. While many symptoms of MS are well-established, the relationship between MS and headaches has been a subject of evolving research and understanding.

A prospective, multicenter study examined headache characteristics during the first clinical event of MS. The results were striking:

78% of patients with newly diagnosed clinically isolated syndrome (CIS) or MS reported headaches within the last 4 weeks
50% experienced throbbing and pulsating headaches
30% reported stabbing headaches
28% had dull and constrictive headaches

This 78% prevalence rate is among the highest reported so far in patients with early MS. It suggests that headaches, particularly those with migrainous features, may be a frequent symptom in the initial manifestation of multiple sclerosis.

Historical Perspective on Headaches in MS

The recognition of headaches as a significant symptom in MS has evolved over time:

Before the 1990s: Prevalence rates for headaches in MS were reported to be relatively low, ranging from 4% to 37.5%
Since 2000: Higher prevalence rates of up to 64% have been reported

This shift in reported prevalence raises questions about whether headaches were previously underrecognized in MS patients or if there have been changes in MS manifestation or diagnostic criteria over time.

Types of Headaches Associated with MS

The study revealed various types of headaches experienced by MS patients:

Throbbing and pulsating headaches (50% of patients)
Stabbing headaches (30% of patients)
Dull and constrictive headaches (28% of patients)

The predominance of throbbing and pulsating headaches suggests a possible link to migraine-type headaches in MS patients. This association could have implications for both diagnosis and treatment strategies.

Potential Pathophysiological Explanations

Recent research has provided intriguing insights into why headaches might be prevalent in MS patients:

Postmortem histological analyses of MS patients’ brains have revealed lymphoid follicle-like structures in the cerebral meninges
These structures could potentially explain the high headache prevalence in MS

The presence of these lymphoid structures suggests that inflammatory processes in the meninges could be contributing to headache symptoms in MS patients. This finding opens up new avenues for research into the underlying mechanisms of MS-related headaches.

Implications for Early MS Diagnosis

The high prevalence of headaches in early MS has significant implications for diagnosis:

Headaches, especially those with migrainous features, could be an early indicator of MS
Patients presenting with specific types of headaches and typical MRI results might be classified as having CIS or early MS instead of radiologically isolated syndrome
Early classification could lead to earlier initiation of immunomodulatory therapy

Recognizing headaches as a potential early symptom of MS could lead to earlier diagnosis and treatment, potentially improving long-term outcomes for patients.

Challenges in Differentiating MS-Related Headaches

While the high prevalence of headaches in early MS is noteworthy, differentiating MS-related headaches from other types of headaches presents challenges:

Headaches are common in the general population
MS and migraine share some risk factors, such as female predominance
The characteristics of MS-related headaches may overlap with other primary headache disorders

Further research is needed to determine if there are specific features that can help identify MS-related headaches and distinguish them from other types of headaches.

Future Directions in MS and Headache Research

The findings of this study and others like it open up several avenues for future research:

Longitudinal studies to track headache patterns throughout the course of MS
Investigation of the relationship between headache characteristics and MS disease activity
Exploration of potential shared pathophysiological mechanisms between MS and primary headache disorders
Development of diagnostic criteria for MS-related headaches
Evaluation of treatment strategies specifically targeting headaches in MS patients

These research directions could lead to improved understanding, diagnosis, and management of headaches in MS patients.

The Impact of Headaches on Quality of Life in MS Patients

Given the high prevalence of headaches in MS patients, it’s important to consider their impact on quality of life:

Headaches can add to the symptom burden of MS
They may contribute to fatigue, a common and debilitating symptom of MS
Frequent headaches could affect cognitive function and work productivity
The presence of headaches might influence treatment decisions and medication choices

Understanding and addressing headaches as part of comprehensive MS care could significantly improve patients’ overall well-being and functioning.

Diagnostic Considerations for Headaches in MS

When evaluating headaches in the context of MS, several factors should be considered:

Timing of headache onset in relation to other MS symptoms
Characteristics of the headache (location, quality, duration, frequency)
Associated symptoms (visual disturbances, sensory changes)
Response to standard headache treatments
Correlation with MS disease activity on imaging

A thorough evaluation of these factors can help determine whether headaches are likely related to MS or represent a comorbid condition.

Treatment Approaches for Headaches in MS Patients

Managing headaches in MS patients may require a multifaceted approach:

Standard headache treatments (e.g., analgesics, triptans for migraine)
Preventive medications if headaches are frequent
Consideration of how MS disease-modifying therapies might affect headaches
Non-pharmacological approaches (stress management, lifestyle modifications)
Treatment of any underlying MS-related inflammation or lesions that could be contributing to headaches

Tailoring treatment to the individual patient’s MS status and headache characteristics is crucial for optimal management.

The Role of Neuroimaging in Evaluating Headaches in MS

Neuroimaging plays a critical role in both MS diagnosis and the evaluation of headaches:

MRI can reveal MS lesions that might be contributing to headache symptoms
Imaging can help rule out other causes of headaches, such as tumors or vascular abnormalities
Serial imaging may show correlations between changes in MS lesions and headache patterns

Integrating neuroimaging findings with clinical presentation is essential for accurate diagnosis and appropriate management of headaches in MS patients.

Comorbidity of MS and Primary Headache Disorders

The relationship between MS and primary headache disorders is complex:

MS patients may have a higher prevalence of migraine compared to the general population
Tension-type headaches are also common in MS patients
The presence of a primary headache disorder may complicate the diagnosis and management of MS-related headaches

Understanding the potential comorbidity of MS and primary headache disorders is important for comprehensive patient care.

Patient Education and Self-Management Strategies

Empowering MS patients to manage their headaches effectively is crucial:

Education about the potential relationship between MS and headaches
Teaching headache tracking and trigger identification
Instruction in relaxation techniques and stress management
Guidance on when to seek medical attention for headaches
Information on lifestyle factors that may influence both MS and headaches

Providing patients with tools and knowledge for self-management can improve outcomes and quality of life.

The Need for Interdisciplinary Approach

Managing headaches in MS patients often requires collaboration between different specialties:

Neurologists specializing in MS
Headache specialists
Neuroradiologists for imaging interpretation
Pain management specialists
Psychologists or psychiatrists for addressing psychological aspects
Physical therapists for managing associated symptoms

An interdisciplinary approach can ensure comprehensive care that addresses all aspects of a patient’s condition.

The high prevalence of headaches in early MS, as demonstrated by the study discussed, highlights the importance of recognizing and addressing this symptom in MS patients. While the exact relationship between MS and headaches is still being elucidated, it’s clear that headaches can significantly impact the lives of those with MS. Future research will likely provide more insights into the mechanisms underlying this association and lead to improved diagnostic and treatment strategies. In the meantime, a comprehensive approach to MS care should include careful evaluation and management of headaches, potentially leading to earlier diagnosis and better outcomes for patients.

Headache in the first manifestation of Multiple Sclerosis – Prospective, multicenter study

Brain Behav. 2017 Dec; 7(12): e00852.

,¹,²,³,¹ and ⁴

Marcel Gebhardt

¹
Krankenhaus Martha‐Maria Halle‐Dölau,
Halle,
Germany,

Peter Kropp

²
Institute of Medical Psychology and Medical Sociology,
Medical Faculty,
University of Rostock,
Rostock,
Germany,

Tim P. Jürgens

³
Department of Neurology,
University Medical Center Rostock,
Rostock,
Germany,

Frank Hoffmann

¹
Krankenhaus Martha‐Maria Halle‐Dölau,
Halle,
Germany,

Uwe K. Zettl

⁴
Department of Neurology,
Neuroimmunological Section,
University of Rostock,
Rostock,
Germany,

¹
Krankenhaus Martha‐Maria Halle‐Dölau,
Halle,
Germany,

²
Institute of Medical Psychology and Medical Sociology,
Medical Faculty,
University of Rostock,
Rostock,
Germany,

³
Department of Neurology,
University Medical Center Rostock,
Rostock,
Germany,

⁴
Department of Neurology,
Neuroimmunological Section,
University of Rostock,
Rostock,
Germany,

Corresponding author. ^*Correspondence
Marcel Gebhardt, Klinik für Neurologie, Krankenhaus Martha‐Maria Halle‐Dölau, Halle, Germany.
Email: [email protected],

Received 2017 Jun 17; Revised 2017 Sep 6; Accepted 2017 Sep 10.

Copyright © 2017 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.This article has been cited by other articles in PMC.

Abstract

Objectives

Multiple sclerosis (MS) is the most frequent immune‐mediated inflammation of the central nervous system that can lead to early disability. Headaches have not been considered as MS‐related symptoms initially, whereas higher prevalence rates were reported since 2000. Postmortem histological analyses of MS patients’ brains revealed lymphoid follicle‐like structures in the cerebral meninges which suggest a possible pathophysiological explanation for the high headache prevalence in MS. The aim of this study was to evaluate headache characteristics during the first clinical event of MS.

Methods

In a prospective, multicenter study, 50 patients with the diagnosis of CIS or MS were recruited. All participants were screened for the presence of headache within the last 4 weeks with help of the Rostock Headache Questionnaire (Rokoko).

Results

Thirty‐nine of fifty questioned patients (78%) reported headaches within the last 4 weeks. Most patients suffered from throbbing and pulsating headaches (25, 50%), 15 (30%) reported stabbing, 14 (28%) dull and constrictive headaches.

Conclusions

Keywords: clinically isolated syndrome, headache, migraine, multiple sclerosis, radiologically isolated syndrome

1. INTRODUCTION

Multiple sclerosis (MS) is the most frequent immune‐mediated inflammation of the central nervous system (CNS) that can lead to early disability (Flachenecker et al., 2008). In 2013, the worldwide MS prevalence was 2.3 million (Browne et al., 2014). The mean age at the first clinical manifestation of MS typically lies between the 20th and 40th year. However, there are also known cases with occurrence from infancy up to well after the 80th year. As in migraine, females are affected 2–3 times more often than males (Flachenecker et al., 2005).

While many symptoms such as paresis, paresthesias and numbness, ataxia, visual disturbances, neuro‐urological dysfunction, neuropsychological deficits, and fatigue often appear in the course of MS, headaches are not regarded as typical early MS symptoms or MS‐related symptoms (Möhrke, Kropp, & Zettl, 2013; Zettl, Stüve, & Patejdl, 2012). Till the 1990s relatively low prevalence rates for headaches in the course of MS were found ranging between 4% and 37.5% (Abb & Schaltenbrand, 1956; Bonduelle & Albaranes, 1962; Clifford & Trotter, 1984; Freedman & Gray, 1989; Poser, Presthus, & Horsda, 1966; Watkins & Espir, 1969), whereas higher prevalence rates of up to 64% were reported since 2000 (Boneschi et al., 2008; D’Amico et al., 2004; Kister et al., 2010; Möhrke et al., 2013; Nicoletti et al., 2008; Putzki et al., 2009; Vacca et al., 2007; Villani et al., 2008).

This high prevalence of headache raises the question whether it is really a comorbidity of two independent diseases or whether the headache could be a primary symptom of MS. Clinically and therapeutically this would be highly relevant, as the presence of headache alone would allow the diagnostic classification as clinically isolated syndrome (CIS) or early MS (Polman et al., 2011) instead of radiologically isolated syndrome (RIS) and could be helpful to assess disease activity (Lublin, 2014). RIS is defined by typical MS lesions found in magnetic resonance imaging (MRI), without the presence of clinical MS symptoms (Okuda et al., 2009).

Postmortem histological analyses of the brains in MS patients revealed the presence of lymphoid follicle‐like structures in the cerebral meninges resulting in meningeal inflammation as a possible pathophysiological explanation for the high prevalence of headache, especially migraine (Magliozzi et al., 2007). It is striking that these tertiary, in particular, B‐cell follicles were found in 41.4% of the patients with secondary progressive MS (SPMS) (Howell et al., 2011; Magliozzi et al., 2010). In addition, there is also a higher number of macrophages, T‐ and B cells in patients with SPMS. SPMS is marked by transition into a continuously progressive form of the disease without the initial relapsing‐remitting phenotype anymore associated with an increase in degeneration. An even higher degree of meningeal inflammation (and consecutively headache) is to be expected with patients in the early stage of the relapsing‐remitting MS (RRMS) or CIS as inflammation is typically predominant here. However, due to the low impairment and mortality in the early stage, postmortem analyses for these patients have not been performed.

Möhrke et al. (2013) reported that MS patients with headaches are younger, more likely female, and less severely affected in their motor functions than those without. The patient cohort consisted of patients with relapsing‐remitting as well as progressive course, but only three patients with CIS.

The aim of this study was to evaluate headache characteristics during the first clinical event when the initial diagnosis of a CIS or MS was made.

2. METHODS

In a prospective, multicenter study 50 consecutive patients with the initial diagnosis of CIS or MS and an occurrence of neurological symptoms within the last 6 months were recruited in the Department of Neurology of Martha‐Maria Hospital and in four private neurological practices in Halle, Germany. The current diagnostic criteria by McDonald (Polman et al., 2011) were met based on an extensive history, clinical examination, MRI of the CNS, and cerebrospinal fluid (CSF) at the time of the first clinical manifestation of neurological symptoms. Exclusion criteria were concomitant diseases known to cause secondary headaches (such as cerebral hemorrhage). There were no screening failures or drop outs.

All study participants underwent in the course of the diagnostic process a detailed and structured clinical interview about their case history and they were asked to complete a semistructured interview covering headache frequency, duration, character, localization, and the presence of accompanying symptoms within the last 4 weeks before hospitalization with help of the Rostock Headache Questionnaire (Rokoko), a validated tool to screen primary headaches (Müller et al., 2014). It allows classification of headaches into migraine with and without aura, tension‐type headache (TTH) and cluster headache. Concerning optic neuritis, we asked especially for pain localized in retro‐orbital, orbital or frontal region, or aggravation by eye movement, so we separated the symptoms from other forms of headache.

Afterward the participants underwent a clinical‐neurological investigation, including the evaluation of disease severity on the Expanded Disability Status Scale (EDSS) (Kurtzke, 1983). Then, a MRI of the central nervous system and a CSF analysis were done. In addition, visual and somatosensory‐evoked potentials were recorded as well as transcranial magnetic stimulation and we determined relevant antibodies for differential diagnostic (Figure ).

This study was approved by the ethics committee of the medical association Saxony‐Anhalt (no. 7/15).

3. RESULTS

Thirty‐nine women (78%) and 11 men (22%) were included. The mean age of the patients was 32.0 years (SD 9.4, min 18, max 54). The latency between the first onset of clinical symptoms to study inclusion amounted from 5 days to a maximum of 6 months. The mean EDSS value was to 1.9 (SD 1.6) (Table ).

Table 1

Sociodemographic and neurological parameters

	N ^a	[%]	Mean	SD
Patients	50
Gender
Male	11 (4)	22
Female	39 (8)	78
Age			32. 0	9.4
EDSS			1.9	1.6
Symptomatic
Monosymptomatic	24	48
Polysymptomatic	26	52
Symptoms^b
Headache	39	78
Paresthesia and numbness	30	60
Paresis	16	32
Optic neuritis	14	28
Brainstem, cerebellar symptoms	9	18
Neuro‐urological dysfunction	2	4
Dysarthria	2	4

Thirty‐nine of fifty patients (78%) reported headaches within the last 4 weeks. According to the criteria of the RoKoKo, seven patients (14%) suffered from TTH, five (10%) from migraine (three without aura, two with aura), 18 (36%) from migraine‐like headaches, and nine (18%) from unclassifiable headaches.

Twenty‐three patients (46%) reported recurrent headaches only, seven (14%) of permanent, and eight (16%) of both recurrent and permanent headaches. Most patients suffered from throbbing and pulsating headaches (25, 50%), 15 (30%) reported stabbing, and 14 (28%) dull and constrictive headaches (Table ).

Table 2

	N	[%]
Pain frequency
Recurrent	23	46
Permanent	7	14
Recurrent and permanent	8	16
Other than that	1	2
Pain character^a
Throbbing and pulsating	25	50
Stabbing	15	30
Dull and constrictive	14	28
Burning	3	6
Nagging	5	10
Duration
<1 hr	2	4
1–3 hr	13	26
4–72 hr	28	56
>72 hr	3	6
Headache medication
Never	21	42
1–4×/month	15	30
5–9×/month	5	10
>=10×/month	9	18
4 weeks after glucocorticosteroid therapy
Small improvement	11	28. 2
Substantial improvement	10	25.6
Completely remitted	8	20.5
Change in location and character	1	2.6
No change	9	23.1

Headaches lasted between 4 and 72 hr in 28 patients (56%). Two patients (4%) also reported having <1 hr of headaches, 13 patients (26%) between 1 and 3 hr and three patients (6%) longer than 72 hr. Eight patients (16%) even reported of longer than 14 days lasting headaches during the last 4 weeks.

Twenty‐one of fifty patients (42%) had taken no headache‐specific medication during the preceding 4 weeks. Fifteen patients (30%) had taken medication for 1–4 days, five (10%) for 5–9 days, and nine patients (18%) for 10 and more days during the last 4 weeks.

A total of 12 patients (24%) reported a positive family history for headaches.

Headaches were the most frequent neurological symptom at the time of the clinical manifestation of the inflammatory CNS disease (CIS, RRMS) (78% of patients).

Thirty patients (60%) suffered from paresthesia (“tingling”) and numbness, 16 (32%) had central paresis. In 14 patients (28%) the disease began with an optic neuritis, in nine (18%) with brainstem or cerebellar symptoms, in two patients (4%) with neuro‐urological dysfunction, and in two patients (4%) with a dysarthria.

All patients received a high‐dose intravenous glucocorticosteroid (GCS) treatment for 5 days with 1000 mg methylprednisolone per day. Four weeks after GCS therapy 11 of the 39 headache patients (28. 2%) reported a small improvement of headaches, 10 (25.6%) a substantial improvement, and in eight (20.5%) patients that the headaches remitted completely. Nine patients (23. 1%) reported no change after the GCS therapy and one patient (2. 6%) noted only a change in headache location and character.

4. DISCUSSION

Headache prevalence was as high as 78% in our group of patients and is therefore among the highest found in patients with CIS or MS. While in other studies, MS patients were examined regardless of their disease duration and course (Abb & Schaltenbrand, 1956; Bonduelle & Albaranes, 1962; Boneschi et al., 2008; Clifford & Trotter, 1984; D’Amico et al., 2004; Freedman & Gray, 1989; Kister et al., 2010; Möhrke et al., 2013; Nicoletti et al., 2008; Poser et al., 1966; Putzki et al., 2009; Vacca et al., 2007; Villani et al., 2008; Watkins & Espir, 1969), well‐characterized patients in the early stages of the disease (namely within the first 6 months after the first manifestation of clinical symptoms) were included in this study. In other studies the mean duration of MS ranged between 14 years (Vacca et al., 2007), respectively, 13.4 years (D’Amico et al., 2004) and 8.8 years (Villani et al., 2008). Compared to the already high 1‐year headache prevalence of 62.5% in the general German population (Straube et al., 2013), it was even higher in our selected population. In addition, it was the most frequent neurological symptom reported by patients, followed by paresis, paresthesia and hypesthesia, optic neuritis, and brainstem or cerebellar symptoms. These further symptoms were also found in other studies in the first manifestations of the disease (Poser, Raun, & Poser, 1982; Weinshenker et al., 1989).

The observed high prevalence of headaches, especially of a migraineous subtype, could be due to a shared pathophysiology. Migraine, which affects significantly more females than males (like MS), has been associated with meningeal inflammation resulting in nociceptive trigeminal activation (Levy, 2009). It has been suggested that inflammatory activity is highest early in the course of MS which would well explain a large overlap with especially migraineous headaches. It is tempting to speculate that headache could in fact be an early symptom of MS itself and not merely coincidental.

Interestingly, Granberg et al. found that in half of the patients with RIS, headaches were the reason for the MRI investigation leading to the incidental diagnosis of RIS (Granberg, Martola, Kristoffersen‐Wiberg, Aspelin, & Fredrikson, 2013). In two of three cases, a progression of MRI lesions can be observed during the next 2 to 5 years, while in the same period, one of three cases fulfill the criteria for “classical” CIS or MS (Granberg et al., 2013). Of great importance is the exact classification between RIS and CIS/RRMS, because studies show that the magnitude of the T2 lesions and signs of neurodegeneration do not differ from RIS patients to patients with early RRMS (Azevedo et al., 2015; De Stefano et al., 2011). These data suggest that if it were possible to define a MS‐typical headache, with the aid of other examinations, patients with these headaches and with typical MRI results would be classified as CIS or early MS instead of RIS and treated with an immunomodulatory therapy (Comi et al. , 2009; Kappos et al., 2006; Miller & Leary, 2009).

More than 50% of our CIS patients suffer from headaches which do not fulfill the formal diagnostic criteria of primary headaches. Most often, recurrent pain of pulsating‐throbbing character was reported lasting between 4 and 72 hr. It could be classified as probable migraine (36%) according to the ICHD‐III (Headache Classification Committee of the International Headache Society, 2013), because they fulfill three of four diagnostic criteria required for a formal diagnosis of migraine and at the same time do not fulfill the criteria of another primary headache. Five patients (10%) even fulfilled all diagnostic criteria of a migraine, so that almost half of all patients suffer from a migraine or a probable migraine; however, only seven (14%) suffer from TTH (test sensitivity/specificity of the RoKoKo of 0.87/0.51 for migraine without aura, 0.71/0.95 for migraine with aura and 0.57/0.93 for TTH). These results are comparable with other studies. In a work of Tabby, Majeed, Youngman, & Wilcox (2013), throbbing headaches were found in 52.9% patients as the most frequent form in 72 MS patients with headaches. D’Amico et al. (2004) found a substantial number of MS patients reported headaches that were classified as probable migraine, because they did not fulfill all diagnostic criteria of a migraine. These also occurred more frequently in patients with RRMS, while TTH was associated with the progressive course of the disease. The strongly differing findings of previous studies on migraine prevalence in MS patients between 19.8% and 82% (Nicoletti et al., 2008; Vacca et al., 2007) and TTH prevalence between 12.2% and 55.2% (D’Amico et al., 2004; Villani et al., 2008) appear to correlate with MS duration.

Pakpoor, Handel, Giovannoni, Dobson, & Ramagopalan (2012) found within the scope of a meta‐analysis that MS patients suffer from migraine more than twice as often as healthy controls. Other studies support a close co‐occurrence of both diseases: in a study of Kister, Munger, Herbert, & Ascherio (2012) patients with migraine had a 39‐fold higher risk of developing MS, while Kruit, van Bucehm, Launer, Terwindt, & Ferrari (2010) reported a correlation of migraine attack frequency with the number of white‐matter lesions. Moreover, it appeared that MS patients with migraine suffered from more relapses than MS patients without migraine (Elliot, 2007; Kister et al., 2010). Another striking similarity between MS and migraine is the high prevalence in young women and the protective effect of pregnancy and lactation. Also undulating courses, episodes with high disease activity over many years and intermittent phases of high disease activity are often observed in both disorders. This raises the question whether migraine headache observed in a large group of MS patients represents a symptomatic headache mimicking migraine or represents an activation of genuine migraine pathology with inflammatory changes as the trigger.

Interestingly, 29 of 39 patients (74.4%) noted an improvement of the headaches following steroid therapy after 4 weeks. Although some studies have questioned the efficacy of steroids in migraine (Fiesseler et al., 2011), there is substantial evidence that steroids interfere with CGRP release (Neeb, Hellen, Hoffmann, Dirnagl, & Reuter, 2016; Neeb et al. , 2015). In status migrainosus, high dose of GCS were effective additively (Rozen, 2002). Therefore, it would be interesting to examine whether patients experience a long‐term improvement of their headaches after short‐time therapy with GCS.

From a pathophysiological perspective, the meningeal inflammation described by Maggliozi et al. involving B‐cell and T‐cell activation in MS patients could also be the cause of headache manifestation. This would also explain why the prevalence of headaches is so high at the beginning of the disease.

Despite the intriguing findings, our study has some shortcomings. Headache characteristics were assessed with the Rokoko‐questionnaire only, which has been shown to have a high diagnostic accuracy (Kurtzke, 1983). However, a relatively large group of patients with headaches could not be allocated to either migraine or tension‐type headache. In a structured clinical interview carried out by a headache expert this could have had reached a higher sensitivity and specificity. In addition, a previous personal history of headaches was not assessed, so that we could not ascertain whether the reported headaches developed de novo in temporal relation to the neurological symptoms leading to the diagnosis of CIS or MS or whether they were just an exacerbation or reoccurrence of a preexisting primary headache. Also the emotional stress prior to the hospitalization could be a reason for exacerbation of migraine and so a potential bias.Due to the lack of an appropriate control group it is difficult to assess whether prevalence rates in our sample are indeed higher than in the general population. However, setting up a matched control group is problematic and would require a large prospective epidemiological study.

5. CONCLUSION

Headaches were prevalent in 78% of patients in our population with newly diagnosed CIS and MS. It is among the highest prevalence rates reported so far in patients with CIS or MS. Thus, headache, especially of a migraneous subtype, is a frequent symptom within the scope of the first manifestation of multiple sclerosis. However, it is not regarded as MS‐related or typical symptom. If it were possible to define a MS‐typical headache, patients with these headaches and with MS‐typical MRI results would be classified as CIS or early MS instead of RIS and treated accordingly with an immunomodulatory therapy. This kind of MS‐typical headache seems to be very similar to migraine, because we often found recurrent pain of pulsating‐throbbing character, lasting between 4 and 72 hr, that does not fulfill the criteria of migraine. Separating these cases from “classical” migraine may help the results of studies, which could show strong differences between MS and migraine in MR morphology (Absinta et al., 2012). According to this it could be an important aim of future MR‐studies to work out differences in MR findings between MS patients with and without headache.

CONSENT FOR PUBLICATION

Not applicable.

AVAILABILITY OF DATA AND MATERIAL

The datasets used and analyzed during this study are available from the corresponding author on reasonable request.

DISCLOSURES

All authors declare that they have no competing interests.

AUTHORS’ CONTRIBUTIONS

Not applicable.

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MS and Migraines: Is There a Link?

Research shows that people with MS tend to have more headaches, including migraines, than others. But scientists aren’t sure if headaches are a symptom of MS, or if the two conditions sometimes just happen to the same people.

The two conditions have different causes, but they share some symptoms. MS happens when your immune system attacks myelin, a protective coating for your nerves. This can cause vision problems, pain, tingling, and weakness.

Scientists don’t know exactly what causes migraines. But they think chemicals and hormones in your body play a role. Along with intense head pain and nausea, migraines sometimes cause visual symptoms called auras. You may see spots, sparkles, or zigzag lines. You might feel tingling, weakness, and dizziness.

Cause or Chance?

Lots of people — 12% of the population — have migraines. But people with MS are more than twice as likely to get migraines, and all headaches, than others.

In some situations, MS can lead to migraines. But sometimes, the two conditions aren’t related. It’s tricky. Consider:

Most people who have MS and migraines had headaches before they were diagnosed with MS.
Others never had a migraine before their first MS symptoms showed up.
Some never learn they have MS until a bad headache leads them to get imaging tests on their brain.

Treatment and Prevention Tips

If you have MS and get a migraine, tell your doctor. Some doctors focus so much on your MS symptoms that they don’t ask if you have migraines. This means you may not get the right treatment for your headaches.

When you talk to your doctor, they can help you figure out if your migraines are related to your MS medications, damage in your brainstem, or an MS flare. Your doctor may change your MS treatment if it makes your migraines worse. If your migraines signal MS flares, your doctor can treat you to prevent a flare-up when you tell them you have a headache.

Other ways to help stop migraines or reduce the pain:

Multiple Sclerosis Foundation – MS and Migraine: More than Meets the Eye

Multiple sclerosis and migraine share a lot more than the first letter of their names.

While many people reading this article have MS, many more people worldwide have migraines and other types of headache. There is a perception that migraine is more common in people with MS, and there is some reason to think that this may be true. However, there are a few issues surrounding migraines and MS that need to be further explored.

Migraines are common (approximately 40 million Americans have migraines), while more than 99 percent of the U.S. population has “ever had a headache.” MS, while not common, is also not rare – it is estimated that 400,000 people in the United States have MS. Many people with MS may have migraines simply because they have one uncommon diagnosis (MS) and one common one (migraine).

So, everyone with a migraine has a headache, but not everyone with a headache has a migraine. There are many other types of headaches. Some people with migraines also happen to have MS and some people with MS have migraines. Sometimes this is simply coincidental, but sometimes the MS itself may be to blame for the migraines.

What is a migraine?

Migraines are a type of primary headache disorder (meaning that they are not generally thought to be caused by something else, like a mass) where a person has headaches that are usually on one side of the head, although the side may change and they may be on both simultaneously. They are usually moderate to severe in intensity, last for longer than four hours if not treated, get worse with activity, feel throbbing and pulsating or are duller or more stabbing. The migraine headache is also accompanied by nausea and/or difficulty with light and loud noises.

While some people have warning signs (often sparkling lights or other visual symptoms) for migraines, called “auras,” this is less common. Migraines without auras are called “common migraines,” while migraines with auras are called “classic migraines.”

Chicken or egg? Which came first?

For most people who have MS and migraines, the migraines came first and are not caused by the MS itself. Some people, however, had no history of migraines prior to their first MS symptoms. In fact, in some cases, a bad headache led to a first brain MRI (magnetic resonance image) which eventually led to a MS diagnosis. Sometimes, however, migraine may be a symptom of MS or even a sign of a MS relapse.

MS is generally thought to be an autoimmune disease with an inflammatory attack on the myelin covering the nerves and the axons themselves within the central nervous system. Migraines are believed to be triggered in a part of the CNS called the brainstem. After the spinal cord and optic nerves, the brainstem is one of the three most common sites for the demyelination seen in MS. This means that a MS lesion in the periaqueductal grey matter may cause a migraine.

MS lesions in the optic nerve, which is called optic neuritis, may be very painful and can make someone feel like they are having the explosive eye pain seen in some migraines. In reality this is a MS lesion causing swelling of the optic nerve (the nerve that transmits signals from the eye), which causes this searing pain.

People with MS may also have migraines because of various medications they are taking, such as migraines triggered by MS disease-modifying treatments, more specifically the beta interferons and fingolimod. While people without a migraine history who take beta interferons may develop headaches as a potential side effect (which also usually improves as the medication is brought up slowly and your body gets used to it), it seems that only people with a personal or family history of migraines actually develop migraines triggered by the MS medications. So, just like many people with migraines know if they have a food or weather trigger for their migraines, MS medications may sometimes be triggers for migraines as well.

Okay, so I have MS and migraines. What do I do about it?

Talk to your neurologist who is treating your MS and let them know that you are having migraines.

This advice is crucial because sometimes neurologists, nurse practitioners and physician assistants may become so focused on your immunological status, relapses, walking, and multitude of other symptoms associated with MS.

In one research trial, we looked at how often different practitioners were diagnosing their MS patients with migraines. At the first analysis, there were surprisingly less people with MS who had migraines than in the rest of the population. When the researchers looked more carefully, however, they found that it made a difference who was seeing the MS patients: the MS specialist reported just as many people with MS had migraines as people without MS have migraines, but the general neurologist and nurse practitioner in this study only had two people with migraines (out of more than 200 MS patients)! It seems unlikely that completely different types of patients were coming to see these different practitioners, and instead it seems that when your health care practitioner is less comfortable with your MS, then they may not take the extra steps to deal with all of your symptoms and other neurologic conditions affecting your life.

The job of physician educators is to help improve the knowledge of doctors and other healthcare practitioners about both MS and migraine, but your help is needed also. Come to your office visits with a list of issues that are troubling you – and if migraines are on that list, then please make sure to bring the topic up.

General approaches to migraines

Once you have informed your neurologist that you have both MS and migraines, your neurologist will try to determine:

A.) Are the MS and migraines related?

B.) Is there an MS lesion that is causing the migraines?

C.) Are the migraines a side effect of a medication?

D.) Treatment options for the migraines.

We have a three-way approach to migraines, similarly to how we approach MS:

1. Prevention

2. Handling symptoms

3. Rescue therapy when things get out of hand

For MS that means:

1. Disease modifying drugs/agents/ treatments (DMDs/DMAs/DMTs)

2. Symptomatic treatments, including Neuro-functional Enhancers (NFEs)

3. Medicines to hasten recovery during a relapse (e.g. intravenous methylprednislonose and injectable ACTH)

For migraines that means:

1. Prophylactic medications – such as antiepileptic medications, blood pressure medications, etc.

2. Abortive medications – such as triptans, NSAIDs, etc.

3. Rescue with occipital nerve blocks and muscle trigger point injections, as well intravenous infusions of medications in and out of the hospital.

Migraine doctors, just like MS doctors, often use complementary therapies, including herbal remedies that have good evidence to support their use.

Although there may not necessarily be a direct link between migraine and MS, with one causing the other, we do know that both MS and migraine should be treated.

As we learn more about MS and migraines, we are finding similarities not just in our approaches to them but also in some of the underlying pathophysiology. In fact sometimes people with migraines but without MS have white spots on their brain MRIs; we are still trying to figure out the exact cause of these spots and to understand what they mean.

Next time you hear about a disease that affects women more than men, the young more than the old, is increased with a family history, where “normal appearing” white matter of the brain may not be completely “normal,” there is an inflammatory soup on the covering of the brain (meninges) and in a quarter of some series patients have white spots on brain MRIs, think migraine.

Daniel Kantor, M.D. is the President of the Florida Society of Neurology, Secretary of the Duval County Medical Society and the Medical Director of Neurologique, an organization dedicated to patient-centered care, research and education. He is board-certified in both Neurology and Headache Medicine and he is the chair of the Education Committee and a board member of the Southern Headache Society. Dr. Kantor focuses on patient-centered MS care and the interactions between MS and migraine. He is a member of the MSF Healthcare Advisory Panel. Dr. Kantor is an investigator in many clinical trials, including those having to do with MS, pain, and headaches.

(Last reviewed 11/2012)

MS and Headaches: Types, Causes, and Treatments

Headaches are common among people with multiple sclerosis (MS). More than 22,000 MyMSTeam members report experiencing this symptom. “I get these headaches,” one member wrote. “I have been told they are MS headaches.”

One small study of people with MS indicated that 78 percent of participants had recently experienced a headache. Despite this, it’s still not known whether headaches should be considered an MS symptom. Migraine headaches are commonly reported by those living with MS, but 40 million people in the U.S. report problems with migraine headaches, making them a common symptom in the general population as well.

What Does a Headache With MS Feel Like?

Most headaches, those associated with MS included, fall into one of three categories: migraine, tension-type headaches, and cluster headaches.

Migraines are severe headaches with throbbing or pulsating pain that is usually focused on one side of the head. They can last from a few hours to days at a time.
Tension headaches are the most common headaches, and feel like a band wrapped around the head. Pain from tension headaches is usually not severe.
Cluster headaches occur in patterns. They’re usually located on one side of the face and are associated with eye redness, runny nose, and facial sweating on the affected side.

A study of 180 people with MS found that 55 percent of participants had experienced headaches in the prior four weeks. No cluster headaches were reported from the group, but 16 people reported a recent migraine and 23 people had recently had a tension headache.

Another type of head pain that is not precisely a headache is trigeminal neuralgia. This is a sharp, stabbing facial pain that usually appears in the cheek or jaw area. Trigeminal neuralgia can be associated with MS, and typically precedes the diagnosis of multiple sclerosis.

How Do Headaches Affect People With MS?

Many MyMSTeam members discuss how headaches can incapacitate them.

“I’ve had a severe headache constantly for over a month, and painkillers do not get rid of them completely.”
“I have a headache/migraine just about every day. They can be extremely painful, and on some occasions I can’t function.”
“It seems that when a stressful situation comes up, I get a headache and my brain feels hot.”
“I started getting migraines and that lasted about a year. Now it comes and goes.”
“I have frequent headaches. They vary in severity, and luckily ibuprofen helps ease the pain!”
“I seem to get headaches more frequently now.”

What Causes Headaches in MS?

There are many reasons why a person living with MS may experience headaches. The study of 180 people with MS found that a person’s MS type may affect whether they experience headaches. In the study, those with relapsing-remitting MS suffered from headaches more often than those with secondary progressive MS. Medication also seemed to have an effect. Half of the participants who hadn’t had a headache recently had also taken corticosteroids. Of those who’d experienced recent headaches, only a quarter had been treated with corticosteroids.

Optic Neuritis

One headache cause specifically related to the progression of MS is optic neuritis, which occurs when the optic nerve in the eye is inflamed. The nerve is directly connected to the brain, and is a major part of the ability to see. One MyMSTeam member with optic neuritis said, “For the past two weeks, I have been getting a bad headache every night. This comes with pain in my eyes and straining to see the TV.”

The most common symptom of optic neuritis is pain behind the eyes when moving them. It is often the first symptom of MS. To determine whether optic neuritis is causing headaches, a neurologist will order an MRI scan. If there is visible damage to the brain, spinal cord, or any two separate areas of the central nervous system — and other diagnoses have been ruled out — MS can be considered as a possible diagnosis. At least one member got a diagnosis following optic neuritis and its associated headaches: “It did start with headaches, where it took me to the ER. They did a brain scan, which only shows my MS.”

Migraine and MS

A study of headache sufferers with MS speculated that migraine and MS could be related by inflammation. Early MS is associated with meningeal inflammation, which is also associated with migraine. “My diagnosis started because of headaches — in the migraine family, but not quite migraines,” one MyMSTeam member said. MS relapse is also associated with a higher rate of migraine.

A meta-analysis studying MS and migraines speculated that demyelination could lead to cortical spreading depression, which is a known risk factor for migraine, or that migraine itself could be an early symptom of MS. A third study gave evidence that interferon beta, used to treat MS, could trigger migraines as a side effect. In the study, 72 percent of participants who had been treated with interferon reported headache as a symptom, whereas only 54 percent of those without headaches had used interferon.

See what MS specialist Dr. Aaron Boster says about managing MS headaches.

Other Headache Triggers

MyMSTeam members often discuss headache triggers. Different medicines have caused headaches for some members. “I just started Copaxone this week, and after each injection, I’ve had a horrible headache that lasts for about 24 hours,” one member said. “I’ve been on Tysabri for 17 infusions now. I have frequent headaches while on it. Varying intensity,” said another. A third member mentioned temperature as a headache trigger. “I get them if I overheat.”

How Is the Headache Treated?

Headache treatments for people with MS will depend on the type of headache. When trigeminal neuralgia is the cause, anticonvulsants are the first line of treatment. “I have this and take Carbamazepine,” one member said. Anticonvulsant drugs work by calming overactive nerve signals. Surgery is prescribed only when drug therapy does not work.

Migraines can be treated with over-the-counter (OTC) medications like Advil (ibuprofen) and aspirin, but only for mild headaches. These drugs can also cause headaches and stomach bleeding if taken for long periods of time.

Prescription drugs used to treat migraine vary in type. Triptans reduce the swelling of blood vessels in the brain and are given as a pill, injection, or nasal spray. D.H.E. 45 (dihydroergotamine), an injection, is given at the onset of a migraine or when an aura is present. Reyvow (lasmiditan) and Ubrelvy (ubrogepant) are two recently developed oral medications that are used to treat migraines.

Some MyMSTeam members discuss migraine medications that worked for them. “Relpax is a super effective migraine med for us,” one said. “I take Topiramate too, 100 milligrams at night. First thing that has finally helped,” another explained.

Most tension headaches usually go away without treatment, but OTC pain relievers may help. Repeated use of them, however, can cause more headaches.

Other methods to relieve headaches have been mentioned by several MyMSTeam members. One advised, “Essential oils (rosemary or basil are other oil options) placed on temples. CBD [where legally available] and chiropractors are good suggestions. Consider acupuncture.”

Cold helped one member with headaches. “I have used ice and cold compresses,” they wrote. Another mentioned a rehydration solution: “The UCAN Hydrate tastes good and works well.” Adequate sleep cycles can also help control headaches.

Talk With Others Who Understand

MyMSTeam is the social network for people with MS and their loved ones. On MyMSTeam, more than 163,000 members come together to ask questions, give advice, and share their stories with others who understand life with multiple sclerosis.

Are you living with MS and headaches? Share your experience in the comments below, or start a conversation by posting on your Activities page.

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