Status migrainosus and migraine aura status in a French tertiary-care center: An 11-year retrospective analysis

Introduction

Five migraine complications are reported in the beta version of the third edition of the International Classification of Headache Disorders, (ICHD-III β) (1): four in the classification itself (status migrainosus (SM), persistent aura without infarction, migrainous infarction and migraine aura-triggered seizure) and one in the appendix (migraine aura status (MAS)). Among these complications, SM and MAS have rarely been studied (2–5). Epidemiology, precipitating factors and evolution are uncertain and pathophysiology is still unknown. We report here 28 consecutive patients diagnosed with SM or MAS over 11 years in one tertiary-care headache center. These cases were identified among patients participating in the French Observatory of Migraine and Headaches (OMH), which is a national clinical research network on headache and facial pain, set up in 2002 by the French Headache Society (6). Characteristics of these patients, the history of their migraine before the occurrence of SM or MAS and the evolution of the disease were analyzed.

Methods

The national OMH network involves 16 tertiary-care headache clinics and one specialized headache emergency department and overall covers approximately two-thirds of the French metropolitan territory. The setting up of the OMH database was declared to and approved by the French Commission on Data Processing and Liberties (6). From the initiation of the OMH in October 2002 to June 2013, 7725 new patients with diagnosis criteria of migraine without aura (MwA) according to the second edition of the International Classification of Headache Disorders (ICHD-II) (7) (code 1.1), and 1096 new patients with the ICHD-II diagnosis criteria of migraine with aura (MA) (1.2.1) consulted in one center (Timone Hospital, Marseille). During the period January 2012 to August 2013, one neurologist reviewed patients’ files of known SM or MAS patients. Diagnostic criteria for SM were headache unremitting for more than 72 hours with severe intensity and debilitating symptoms and for MAS were two auras per days over at least five consecutive days in MA patients. New consulting patients diagnosed with SM or MAS were also recruited. All patients’ files were reviewed by the same physician. SM or MAS diagnosis was established according to ICHD-II (code 1.5.3 and A1.2.7, respectively). However, we have selected only patients who suffered from debilitating headache in order to exclude migraine attacks with multiple recurrences. If necessary, complementary information was obtained for some patients by post mail and by phone call.

We captured information on each patient’s demographic, characteristics of usual migraine attacks (MA or MwA), and frequency of migraine attacks by using a patient migraine diary. Frequency of migraine attacks was classified as low-frequency migraine, which was defined as between 0 to nine days of migraine per month for three months; high-frequency migraine, when there were between 10 to 14 days of migraine per month for three months; and chronic migraine and/or medication-overuse headache, when there were more than 15 days of headache per month for three months. We also collected the following data: duration of the complication, delay between onset of the migraine disease and SM or MAS, precipitating factors, prophylactic treatment before the complication (prophylactic treatment was considered effective when it reduced 50% of attacks), changes in frequency or/and intensity of the attacks three months before complication occurrence. Finally, the management of SM and MAS and the course of the disease (frequency of migraine attacks in the three months following SM or MAS, occurrence of new SM or MAS during the follow-up) also were studied.

Results

Among the 8821 patients consulting from October 2002 to June 2013 in our participating OMH center, we found 28 (3%) who were diagnosed with SM or MAS. Mean follow-up of the patients was 49 months. Out of 28 patients studied, 24 suffered from SM, three from MAS and one from both.

SM

Patients and characteristics of migraine before SM

Patient characteristics are displayed in Table 1. Of the 25 patients who experienced SM, 21 are women and four are men. Mean patient age was 39, ranging from 25 to 71 years-old. Twenty-one patients had MwA and four patients had both MwA and MA. Among these four patients, three patients had visual aura between one and three per month, including the patient who suffered both from SM and MAS, and one patient had, once a month, aura with visual symptoms, sensory symptoms, aphasic symptoms and sometimes motor deficit. Before SM, 20 had low-frequency migraine, four patients high-frequency migraine and one patient chronic migraine.

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Table 1.

Patient characteristics with status migrainosus (SM).

n = 25
Age in the first episode (mean in years)	39 (25–71)
Sex (male:female)	4:21
Migraine characteristics before SM
MwA	21
MwA and MA	4
Precipitating factors	16
Stress/anxiety	11 (68.8%)
Menstruation	5 (31.3%)
Lack of sleep	1 (6.3%)
Delay between complication and onset of migraine
0–10 years	4
10–20 years	7
20–30 years	8
30–40 years	3
40–50 years	1
50–60 years	2
Duration of SM	4.8 weeks (3–10)
Hospitalization	15
Relapse of SM	8 (32%)
Delay of relapse (months)	61.4
Follow‐up duration (months)	45.3

MwA: migraine without aura; MA: migraine with aura.

SM characteristics

Mean duration of SM was 4.8 weeks (range three to 10 weeks). Delay between onset of migraine and SM was variable, but more frequently between 10 and 30 years of evolution (n = 15). Precipitating factors were found for 16 patients (64%). Stress (68.8%) and menstruation (31.3%) were the main precipitating factors.

Modification of migraine characteristics before SM

Nine patients described changes in migraine intensity in the three preceding months, with attacks described as more painful and/or migraine attacks with longer duration (36%). In contrast, no change in the frequency of attacks was found. Twelve patients had prophylactic treatment during the six months before SM occurred. Prophylactic treatment was effective in three, had only a partial effect in two (reduction of the attacks intensity) and ineffective in four. Data are missing for three patients.

Evolution

During follow-up, eight patients (32%) had a new episode of SM, occurring with variable delay (mean = 61 months). The only patient who suffered from SM and MAS presented with two episodes of SM and one episode of MAS during follow-up (96 months). Twenty-three of 25 patients had similar migraine attack frequency before and after SM. All patients with low-frequency migraine attacks before SM returned to low-frequency migraine attacks after. Among patients with high-frequency migraine attacks (n = 4), half returned to high frequency, one to low frequency and one to chronic migraine (Table 2).

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Table 2.

Migraine attacks frequency before and after status migrainosus (SM).

Migraine attack frequency before SM	n	Evolution of migraine attack frequency three to six months after SM	n
Low frequency	20	Low frequency	21
High frequency	4	High frequency	2
Chronic migraine	1	Chronic migraine	2

Management

The majority of patients (n = 15) were hospitalized (60%) in order to receive amitriptyline intravenous treatment (25–75 mg/d adjusted on the basis of tolerance and efficacy). The mean duration of hospitalization was six days. All the patients were migraine free at the end of the intravenous treatment. In these patients oral amitriptyline was continued after as prophylactic treatment. No patient received corticosteroids. Six patients (24%) had sick leaves and used nonspecific analgesics such as acetaminophen or nonsteroidal anti-inflammatory drugs. Four patients received other prophylactic treatment.

Discussion

SM and MAS are rare but their exact prevalence is unknown, SM being probably more frequent than MAS. In our study, the occurrence of SM and/or MAS was a rare event affecting 3% of our patients. SM was largely more frequent than MAS, with one patient having both SM and MAS. This is the first case of a patient having both SM and MAS described in the literature.

This series of 28 SM and/or MAS patients diagnosed over 11 years in one specialist headache center in the South of France is the first describing the clinical characteristics and evolution of SM or MAS. Nearly one-third of our patients described a second episode of SM or MAS during the follow-up. There was no link between the severity of the migraine and the occurrence of SM or MAS. In fact, SM or MAS occurred in a great majority in patients with low-frequency migraine attacks. Moreover, frequency of migraine attacks before and after each episode was roughly the same in our population.

Further to the first description by Taverner (8) in 1978 of extended and severe migraine attacks, Couch and Diamond (2) defined SM in 1983 and diagnostic criteria were proposed in the first International Classification of Headache Disorders (ICHD-I) in 1988 (9). This migraine complication (1.6.1) was defined in the MA or MwA patient as an attack lasting more than 72 hours. ICHD-II defined SM (1.5.3) as headache unremitting for more than 72 hours with severe intensity. The notion of debilitating attacks was in the description but not in the criteria. Recently, the ICHD-III β defines SM (1.4.1) as debilitating migraine attacks lasting more than 72 hours in MA and MwA patients. Our study has collected patients seen between October 2002 and August 2013, and used ICHD-II criteria to recruit patients. Systematically we added the notion of debilitating episodes to exclude migraine attacks with multiple recurrences. Debilitating symptoms are necessary criteria in the new International Headache Society (IHS) classification.

Nearly 20% of migraine patients reported that their MwA attacks lasted more than 72 hours, which is one of the criteria of the SM definition (5). This fact underlines the crucial necessity of having both criteria for length of the attack and debilitating character. Moreover, in our data, mean duration of SM was 4.8 weeks; we have probably recruited severe SM or MAS because we work in a tertiary center.

The first report on SM (2) was a retrospective study in which 126 physicians were asked about precipitating factors, criteria to hospitalize patients and management. Our study is the third performed in a tertiary medical center after Jauslin et al.’s study (3) and Wang et al.’s study (4) and is the first that evaluates the modification of migraine characteristics before SM and the evolution of the frequency of the attacks after SM. The previous studies essentially analyzed the management of SM.

‘Migraine aura status’ was first mentioned in 1982 by Haas (10). ICHD-I did not mention MAS. ICHD-II integrated it into the appendix, but not as a migraine complication (A1.2.7). It was defined as two auras per days over at least five consecutive days in the MA patient. In ICHD-III, MAS (A1.4.5) was still mentioned in the appendix but as a migraine complication. It’s now defined as two auras per day over at least three consecutive days in the MA patient. ICHD-II criteria were strictly used for our study.

Couch and Diamond (2) have noted that stress (67.5%), depression (30.2%), medication overuse (29.4%) and anxiety (27.0%) were the main precipitating factors. In our study, stress was the most important precipitating factors (68.7%), confirming Couch and Diamond’s data. Menstruation was found in 31.2% patients in our study. The role of hormonal changes in women has been suggested but no formal study confirming this data is available. Medication overuse was considered as a precipitating factor by Couch and Zagami but this crucial point was not discussed in ICHD-II (11). The ICHD-III notes that patients with medication overuse should be excluded. One of our patients had chronic migraine and persistent medication overuse despite several drug withdrawals; but SM was diagnosed because his headache was unusually debilitating. No precipitating factors were found in our study for MAS.

According to the current literature, the evolution after SM or MAS is not described. Nearly one-third of our patients (32%) described a second episode of SM and three out of four a new episode of MAS.

In addition, a great majority of our patients have the same migraine attack frequency before and after their SM or MAS (26/28 patients). In the majority of cases, SM/MAS occurred in patients presenting with low-frequency migraine attacks. This suggests that SM or MAS has an accidental occurrence in patients with nonsevere migraine and does not change the general evolution of the disease.

Management of SM and MAS is not well established. Hospitalization was required in case of lack of relief with medication, intense pain, nausea and vomiting or debilitating episode in Couch and Diamond’s study (2). In our series, a majority of patients had to be hospitalized (60%). As far as the treatment of SM is concerned, dihydroergotamine, intravenous lidocaine, neuroleptics, corticosteroids or narcotics are usually proposed (5,10,11).

In our experience, amitriptyline is the most used (60%) treatment with good efficacy and tolerance. Twenty-four percent of the patients had ambulatory treatment with nonspecific analgesics, with similar good outcome.

In our study, 50% patients describing MAS received lamotrigine with efficacy and 50% had spontaneous resolution.

In conclusion, our results highlight a high rate of relapse and a similar frequency of migraine attacks before and after SM. However, these results should be used with caution since it was a retrospective study in a tertiary medical center. This study should be complemented by a prospective study to confirm these results.

Clinical implications

Description of patient characteristics, modifications of the migraine before complication, evolution after the episode and management in patients who had status migrainosus