Headaches In Multiple Sclerosis

The aim was to investigate the lifetime prevalence of Headache and primary Headache (diagnoses according to International Headache Society criteria) in Multiple Sclerosis (MS).

The relationships between Headache and clinical features of MS and MS therapy were also investigated. We studied 137 patients with Clinically Definite MS; 88 reported Headache, 21 of whom developed Headache after the initiation of Interferon.

The prevalence of all Headaches in the remaining 116 patients was 57.7%. Migraine was found in 25.0%, tension-type Headache in 31.9%, and cluster Headache in one patient.

A significant correlation (P = 0.007, Fisher's exact test) between Migraine and Relapsing/Remitting MS was found. Primary Headaches are common in MS patients.

Further studies are needed to clarify the mechanisms underlying this association, particularly the association between Migraine and Relapsing-/Remitting MS, and the role of Interferon in the development of new Headache.

The subcommittee of the International Headache Society for Headache classification (ICHD-II) has recently recognized that secondary Headaches may occur in patients affected by inflammatory diseases (ID) of the Central Nervous System (CNS).

Classifying them among the Headaches attributed to Non-Vascular IntraCranial Disorders.

The aim of the study was to verify the association between Headache and inflammatory non-infectious diseases of the CNS, by a review of the literature data on the topic, integrated by personal cases and data.

Secondary Headaches may occur in four main disorders: NeuroSarcoidosis (sec 7.3.1), Aseptic (non-infectious) Meningitis (7.3.2), other non-infectious ID (7.3.3) and Lymphocytic Hypophysitis (7.3.4).

Headache and/or primary Headaches are frequently reported in patients with NeuroSarcoidosis (30%), Behcet's Syndrome (BS) (55%) and acute Disseminated Encephalomyelitis (45-58%).

Recent data show a high incidence of Headache also in Multiple Sclerosis (MS) (58%) (not mentioned in ICHD-II).

The association between Headache and Inflammatory Dysimmune Diseases of the CNS, in particular BS and MS, might suggest a pathogenetic relationship.

Type and frequency of Headaches during ImmunoModulatory Therapy in MS were determined in 167 consecutive patients.

In a prospective group of 65 patients beginning Interferon-ß therapy, Headache frequency and duration increased in 18% of all and in 35% of patients with pre-existing Headache by more than 50% during the first 6 months.

In two retrospective groups, increased Headache frequency was reported by 34% of 53 patients on Interferon-ß, but by only 6% of 49 patients during at least 6 months of Glatiramer Acetate therapy.

Three Double-blind, Randomized, Placebo-Controlled Trials:
Arch Neurol 1998;55:210-217 February 1998
Richard B. Lipton, MD; Walter F. Stewart, PhD, MPH; Robert E. Ryan, Jr, MD; Joel Saper, MD; Stephen Silberstein, MD; Fred Sheftell, MD

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Objective
To determine if the prevalence of Migraine-like Headache in patients with Multiple Sclerosis (MS) is associated with plaques in the BrainStem or in other locations.

Background
There is increasing evidence to suggest that PeriAqueductal Gray Matter (PAG) plays a role in the pathophysiology of Migraine Headache. There are a few clinical case studies and some experimental evidence in support of this observation.

Methods
The study population of patients with DeMyelinating Disease was identified by accessing the Department of Radiology Magnetic Resonance Imaging (MRI) database accumulated between the years of December 1992 and June 2002.

A total of 4369 MRI scan reports were available for review from that time period. Out of this, 1533 studies were reported to have possible DeMyelinating lesions.

Medical records of these patients were reviewed to confirm the diagnosis of MS and also to document the Headache complaints, if any. Two hundred and seventy-seven patients were identified with definite MS.

A questionnaire was mailed to these patients to obtain additional details regarding MS and Headache. The questionnaire response rate was 61% (169 of 277).

This data were added to the information previously obtained from the medical records. The MRI films of each patient were examined, documenting location of the plaque, rather than the actual number.

MRI and clinical data were kept separate until the final analysis. The International Headache Society criteria were used to classify Headache types.

Results
There were 207 female and 70 male patients available for analysis.

Sixty-six percent (182 of 277) of patients were diagnosed with Relapsing/Remitting MS, 17% (47 of 277) with Primary/Progressive MS, and 17% (48 of 277) with Secondary/Progressive MS.

Overall, 55.6% (154 of 277) of patients had a complaint of Headache.

Of these patients, 61.7% (95 of 154) met criteria for Migraine-like Headache, 25.3% (39 of 154) met criteria for Tension-type Headache, and 13% (20 of 154) had features of Migraine and Tension-type Headache.

MS patients with a plaque within the MidBrain/PeriAqueductal Gray Matter areas had a four-fold increase in Migraine-like Headaches (odds ratio 3.91, 95% confidence interval 2.01 to 7.32; P < .0001).

A 2.5-fold increase in Tension-type Headaches (odds ratio 2.58, 95% confidence interval 1.13 to 5.85; P= .02).

And, a 2.7-fold increase in combination of Migraine and Tension-type Headaches (odds ratio 2.77, 95% confidence interval 0.98 to 7.82; P= .05) when compared to MS patients without a MidBrain/PeriAqueductal Gray Matter lesion.

Although not statistically significant, MS patients with three or more lesion locations were found to be approximately two times more likely to have Migraine-like Headaches.

Compared to MS patients with 0 to 2 locations (3 to 5: odds ratio 2.47, 95% confidence interval 0.90 to 6.84; 6 to 8 locations: 1.82, 0.64 to 5.17; > or =9 locations: 2.41, 0.63 to 9.13).

A linear trend was also observed between numbers of lesion locations and Migraine-like Headaches (P= .02).

Conclusion
The results of this study indicate that the presence of a MidBrain plaque in patients with MS is associated with an increased likelihood of Headache with Migraine characteristics.

(Headache 2005;45:670-677).

Background
In patients with Migraine, functional changes have been described in the Red Nucleus (RN), Substantia Nigra (SN) and PeriAqueductal Gray Matter (PAG).

Purpose
To evaluate whether and at which frequency these structures are involved by MRI-detectable structural abnormalities in Migraineurs and to investigate the pathogenic role of these abnormalities by assessing their frequency and extent in patients with Multiple Sclerosis (MS) and Migraine.

Methods
On Brain dual-echo scans obtained from 58 Migraineurs (40 without and 18 with Aura), 37 MS patients with Migraine without aura and 42 MS patients without Migraine.

The presence of HyperIntense lesions involving the BrainStem structures was recorded.

A test of heterogeneity between groups was used to compare the presence of lesions among patient groups.

Results
Lesions of RN, SN and PAG were found in all patient groups, with frequency from 57.5% to 86.5%.

Significant between-group differences for all these regions were found. No difference was found between Migraine patients with and without Aura.

Compared with MS patients without Migraine, MS patients with Migraine had more significant involvement of the SN (p=0.02) and RN (p < 0.0001).

Compared with Migraine patients, MS patients with Migraine had more significant involvement of the SN and PAG (p ranging from 0.009 to 0.02).

Conclusions
T₂-visible lesions in the BrainStem are frequent in patients with Migraine, but do not seem to be associated with the presence of Aura.

DeMyelinating lesions in the RN, SN and PAG might be among the factors responsible for the presence of Migraine in patients with MS.

Background And Purpose
In Migraine patients, functional imaging studies have shown changes in several Brain Gray Matter (GM) regions. However, 1.5-T MRI has failed to detect any structural abnormality of these regions.

We used a 3-T MRI scanner and Voxel-Based Morphometry (VBM) to assess whether GM density abnormalities can be seen in patients with Migraine with T₂-visible abnormalities and to grade their extent.

Methods
In 16 Migraine patients with T₂-visible abnormalities and 15 matched controls, we acquired a T₂-weighted and a high-resolution T₁-weighted sequence.

Lesion loads were measured on T₂-weighted images.

An optimized version of VBM analysis was used to assess regional differences in GM densities on T₁-weighted scans of patients versus controls.

Statistical parametric maps were thresholded at P<0.001, uncorrected for multiple comparisons.

Results
Compared with controls, Migraine patients had areas of reduced GM density, mainly located in the Frontal and Temporal Lobes.

Conversely, patients showed increased periacqueductal GM (PAG) density.

Compared with patients without aura, Migraine patients with aura had increased density of the PAG and of the Dorsolateral Pons.

In Migraine patients, reduced GM density was strongly related to age, disease duration, and T₂-visible lesion load (r ranging from -0.84 to -0.73).

Conclusions
Structural GM abnormalities can be detected in Migraine patients with Brain T₂-visible lesions using VBM and a high-field MRI scanner.

Such GM changes comprise areas with reduced and increased density and are likely related to the pathological substrates associated with this disease.