ISSN 0017-8748 doi: 10.1111/head.12545 Published by Wiley Periodicals, Inc.
Headache © 2015 American Headache Society
Brief Communications Transient Global Amnesia Triggered by Migraine in a French Tertiary-Care Center: An 11-Year Retrospective Analysis Anne Donnet, MD
Objective.—The etiology of transient global amnesia (TGA) remains unclear, and flow disturbances in the mesial temporal lobes secondary to venous congestion have been proposed as a potential cause. The occurrence of TGA during a migraine attack is a rare condition. Methods.—This 11-year retrospective study in one French center describes patients’ characteristics, type of migraine, investigations, treatment with vasoconstrictor during the TGA/migraine attack, and outcome in patients who had TGA during a migraine attack. Results.—Among 8821 new patients, 6 cases of TGA occurring during a migraine attack were identified. For a majority of patients, TGA occurs after the beginning of the attack. TGA always occurs during a severe migraine attack, with vomiting or vomiting efforts. Vomiting or vomiting efforts always precede a TGA episode. Conclusions.—TGA occurring during a migraine attack is rare. Since a Valsalva maneuver, such as forceful vomiting, is frequently described at the origin of the attack, blocking venous return through the superior venous cava may allow brief retrograde transmission of high venous pressure from the arms to the cerebral venous system, resulting in venous ischemia to the diencephalon or mesial temporal lobes and causing TGA. Key words: transient global amnesia, migraine, cortical spreading depression-migrainous aura (Headache 2015;55:853-859)
TGA have been widely discussed.2 TGA is classically associated with a past history of migraine with or without aura.3 Headaches may also occur during a TGA episode.3 However, the occurrence of TGA during a migraine attack is a rare condition. Six observations of TGA occurring during a migraine attack are presented and discussed.
Transient global amnesia (TGA) is the inability to retain new information and to recall past events during a period of minutes or hours. Its etiology is unclear, and flow disturbances in the mesial temporal lobes secondary to venous congestion have been proposed as a potential cause. Ultrasonographic evaluation of the internal jugular vein (IJV) has demonstrated valvular insufficiency in TGA.1 Pathophysiological mechanisms linking migraine and
Address all correspondence to A. Donnet, Centre d’Evaluation et de Traitement de la Douleur, Hôpital Timone, 264 Boulevard Saint-Pierre, 13385 Marseille Cedex 05, France.
METHODS AND CASE REPORTS Between October 2002 and June 2013, a total of 7725 new patients with diagnosis criteria of migraine without aura (MWoA) according to the second edition of the International Classification of Headache Disorders (ICHD-II)4 (code 1.1), and 1096 new patients with the ICHD-II diagnosis criteria of
Accepted for publication February 2, 2015.
Conflict of Interest: None.
From the Centre d’Evaluation et de Traitement de la Douleur, Hôpital Timone, Marseille, France (A. Donnet).
853
854 migraine with aura (MWA) (1.2.1) consulted in our center (Timone Hospital, Marseille). Six cases of TGA occurring during a migraine attack were identified among Marseille’s 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.5 The French 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. One neurologist reviewed the files of patients with known TGA occurring during a migraine attack. We used the criteria of TGA as defined by Hodges:6 pure loss of fixation memory, no impairment of alertness, self-identity, or other focal neurological involvement, ceasing within 12 hours, and associated with repetitive questioning and anxiety. New consulting patients diagnosed with TGA occurring during a migraine attack were also recruited. Frequency of migraine attacks was classified as lowfrequency migraine, which was defined as between 0 and 9 days of migraine per month for 3 months; highfrequency migraine, when there were between 10 and 14 days of migraine per month for 3 months; and chronic migraine and/or medication-overuse headache, when there were more than 15 days of headache per month for 3 months.
RESULTS Among the 8821 new patients consulting from October 2002 to June 2013 in our participating OMH center, we found 6 (6.8 TGA per 10,000 new patients) who were diagnosed with TGA occurring during a migraine attack. Patients’ characteristics are displayed in Table 1. Of these 6 patients, 5 were women. Median patient age at the time of TGA was 54.2 (44-66 years). Migraine Characteristics.—Five patients have a personal history of MWoA. One patient has both MWoA and MWA. TGA occurring during a migraine
June 2015 attack always occurred in patients with low-frequency migraine attacks. TGA always occurs during a severe migraine attack, with vomiting (5/6) or vomiting efforts (1/6). Vomiting or vomiting efforts always precede a TGA episode. Two patients had taken a vasoconstrictor (zolmitriptan or almotriptan) during the headache. TGA Characteristics.—All patients had TGA conforming to Hodges’ definition.6 All patients – except one – reported a triggering event: emotional stress (1), departure for a long trip (1), cold weather (snow) (1), beginning of the holidays (1), professional overwork (1). All patients had TGA in the presence of a witness, which allowed for reconstruction of the precise progress of the attack. Mean duration of TGA was 6 hours (4-8). All patients except one had experienced a single episode of TGA. Only one patient had TGA recurrences 11 and 12 years after the first episode. The second and third episodes of TGA occurred after the patient had been migraine-free for several years, and TGA was not accompanied or followed by headache. His brother also complained of recurrent TGA.
DISCUSSION TGA is defined by a sudden onset of anterograde and retrograde amnesia that lasts up to 24 hours. It is a rare event: epidemiological studies show that the incidence of TGA ranges between 3 and 8 per 100,000 people per year. Seventy-five percent of attacks occur in people between 50 and 70 years of age, and occurrence in patients younger than 40 years of age is rare.2 In most cases, TGA occurs once in a lifetime, and the same patient rarely presents another amnestic episode. The nature of precipitating events has been studied and Valsalva-associated maneuvers, emotional stress, or sudden contact with cold have been described.7 The underlying pathomechanism of TGA is still under discussion. Reversible diffusion-weighted imaging hyperintensities in the hippocampus have recently been found in magnetic resonance imaging (MRI) of patients with TGA during acute events. These focal lesions can be consistently detected in the CA1 field in the cornu ammonis.2 Proposed
MWoA since adolescence
MWoA since adolescence
MWoA since adolescence
MWoA since adolescence MWA (visual, paresthesic, and aphasic aura). Rare occurrence but very severe MWA
MWoA since adolescence
F/62
F/66
F/44
F/46 ans
F/62
TGA
2014 beginning with nausea, vomiting, pallor followed by TGA Severe headache after TGA Duration of TGA attack = 8 hours No precipitating factor
2010 MWA Visual, paresthesic, and aphasic aura followed by a severe headache with vomiting and TGA Duration of TGA attack = 5-6 hours Precipitating factor: beginning of the holidays
2002 Severe headache with vomiting followed by TGA Duration of TGA attack = 4 hours Precipitating factor: professional outwork
2001 Severe headache, nausea, vomiting effort followed by TGA Duration of TGA attack = 6-8 hours
2009 Severe headache with vomiting followed by TGA Duration of TGA = 5 hours Precipitating factor: departure for a long journey
1999 Severe headache with vomiting followed by TGA Duration of TGA = 7 hours Precipitating factor: cold weather (snow)
MWA = migraine with aura; MWoA = migraine without aura.
MWoA since adolescence Attacks were severe, with a frequency of 1 or 2 per week
Type of Migraine
M/55
Sex/Age at Time of TGA
Almotriptan during headache
Zolmitriptan during the headache
No
No
No
Treatment With Vasoconstrictor During the TGA/Migraine Attack
Table 1.—Patients’ Characteristics
CT scan and cerebral MRI
EEG-cerebral MRI (normal)
Cerebral MRI (normal)
CT scan and cerebral MRI
EEG, cerebral MRI (normal)
Lumbar puncture-EEG-cerebral MRI (normal)
Investigations
Rare MWoA attacks
No follow up since 2003
Last follow up 2011: MWoA attacks with a low frequency
MWoA 3 or 4 attacks per month
No migraine attack since 2003 Recurrence of TGA in 2010 and in 2012 without migraine attack
Outcome
Headache 855
856 mechanisms include hippocampal ischemic events, epilepsy, and migraine. Recently, the hypothesis that transient retrograde venous congestion and venous ischemia of temporobasal structures cause TGA has been suggested.1,8 Since a Valsalva maneuver is frequently described at the origin of the attack, the blocking of venous return through the superior venous cava may allow brief retrograde transmission of high venous pressure from the arms to the cerebral venous system; this results in venous ischemia in the diencephalon or mesial temporal lobes and in TGA.8 An incompetent jugular valve would make patients more susceptible to retrograde venous flow. In fact, a higher prevalence of IJV valve incompetence has been described in TGA patients,9 and retrograde intracranial venous flow caused by left brachiocephalic vein compression was demonstrated only in patients with TGA.10 However, its contributing role in TGA pathogenesis is still debated. Schreiber et al9 hypothesized that Valsalva maneuvers and venous outflow occur only as a cofactor, and that the underlying mechanism of TGA is probably multifactorial. On the other hand, migraine is a frequent disease. The current overall prevalence of migraine in France is estimated at 21.3% according to the IHS (International Headache Society) classification.11 Prevalence is highest in women, and in people between the ages of 25 and 55 years. Everything seemed to oppose these 2 diseases. Nonetheless, a comorbidity between TGA and migraine is suggested on large series of patients, suggesting a prevalence of migraine in TGA patients; the link between the two, however, needs to be clarified.2,3 Moreover, TGA and migraine share common precipitating factors.3 TGA has been considered as a migrainous aura12 (Table 2). Olesen et al12 hypothesized that TGA might occur as a consequence of cortical spreading depression (CSD) in the hippocampus. They suggest that the events that trigger TGA cause the release of glutamate in the hippocampi, triggering migrainous CSD and transient hippocampal dysfunction. CSD in the hippocampus might affect CA1 neuronal function, and induce cellular metabolic changes resulting in TGA.13 The usual age distribution of TGA, the triggering events that provoke it, and the recent MRI
June 2015 findings are arguments against migrainous CSD as the cause of TGA.14 A case control study argues against the hypothesis that TGA represents a type of migraine aura or migraine equivalent.15 However, current studies in CSD confirm that this phenomenon plays an important role in some neurologic disorders, including migraine, but also TGA, cerebrovascular disorders, and head injury. If MWoA is predominant in our study, the possible role of CSD cannot be excluded. TGA occurring during a migraine attack has been rarely reported (Table 2). Some observations in pediatric population are probably related to migrainous complex aura (basilar-type migraine16 or confusional migraine).17,18 TGA, after administration of vasoconstrictors for migraine treatment, is reported in 4 cases.19-21 One case of TGA associated with MWA during cardiac catheterization has been described.22 Besides these particular cases, 2 situations can be described. In the first, TGA occurs before the migraine attack and can be considered as a migrainous aura.23,24 This is an exceptional occurrence, with 4 cases reported in the literature (3 women and 1 man aged 38-70). Two patients have had MWA after the TGA; one patient had visual aura without migrainous headache after the TGA. On the other hand, TGA may occur after the beginning of the migraine attack.19,25-28 Our case reports have several specific points of interest. First, they confirm that TGA occurring during a migraine attack occurs, in a large majority of cases, after the beginning of the headache and during a severe attack. Second, 5 patients have MWoA exclusively, and in one it is associated with MWA and without aura. The existence of TGA after the beginning of the headache, and the predominance of MWoA between subjects are not in favor of the role of CSD. Third, the existence of vomiting or vomiting efforts is systematically described. A Valsalva maneuver seems to be the major precipitating factor for TGA due to the systematic presence of vomiting. Fourth, the role of patent foramen ovale (PFO) may be discussed. Epidemiological data suggest a bidirectional link between PFO and MWA with a
Headache
857
Table 2.—Characteristics of Patients With Transient Global Amnesia Occurring During a Migraine Attack
TGA during the migraine
TGA before the migraine
Basilar-type or confusional migraine Ergotamine
Catheterization
Sex
Age
MWoA/MWA
M M M M
46 36 43 57
M
31
MWA MWA MWA MWA followed by TGA – recurrent episodes MWoA, MWA
F M
59 68
MWoA, MWA MWoA
M
60
MWoA
F
64
MWoA, MWA
M
38
MWoA, MWA
F
55
MWA
F
70
MWoA
M M F F F
9 16 13 13 54
Basilar-type migraine MWoA Basilar-type migraine Basilar-type migraine MWoA
F F F
65 63 58
MWoA MWoA MWoA before TGA
M
50
MWA
Comments
References
Caplan et al, 19813
Seven cases of TGA associated with headache MWoA attack followed by TGA Recurrent attacks of MWoA followed by TGA MWoA attack followed by TGA MWoA followed by TGA Recurrent attacks of MWoA followed by TGA MWoA followed by TGA Two episodes of TGA before MWoA Two attacks of TGA followed by immediate migraine without aura TGA immediately followed by visual aura without headache Recurrent episodes of transient global amnesia followed by intense headache
Crowell, 198428 Sacquegna et al, 198626 Caffara et al, 198825 Maggioni et al, 201127 Maggioni et al, 201127 Dupuis et al, 198724 Montagna et al, 200023 Montagna et al, 200023 Dalla Volta et al, 201412
? No headache ? ? ? MWoA before TGA Cerebral MRI: right thalamic infarct Vasoconstrictors as treatment of migraine (dihydroergotamine, sumatriptan) Ergotamine Dihydroergotamine Ergotamine
Amit et al, 198617 Tosi et al, 199716
MWA before TGA After catheterization Cerebral MRI: left temporal ischemic lesion
Fernandez et al, 200522
Tosi et al, 199716 Pradalier et al, 200021
Gil-Martinez et al, 200420 Olivarius et al, 197919
MWA = migraine with aura; MWoA = migraine without aura.
relative risk of 2 for PFO in subjects with MWA and for MWA in subjects with PFO. There is no evidence for a link between PFO and MWoA. This link is not systematic and applies only to subsets of PFO, mostly large ones. A coincidence of 2 conditions, however, does not necessarily imply a causal relationship.29 Results on the role of PFO in TGA are controversial.30,31 The existence of PFO has not been
researched in our patients. Finally, TGA may be the consequence of multiple pathophysiological mechanisms, rather than the result of a single cause. However, a Valsalva maneuver, such as vomiting, described at the origin of the attack, which allows brief retrograde transmission of high venous pressure to the cerebral venous system, seems to be the common initial symptom.
858
STATEMENT OF AUTHORSHIP Category 1 (a) Conception and Design Anne Donnet (b) Acquisition of Data Anne Donnet (c) Analysis and Interpretation of Data Anne Donnet Category 2 (a) Drafting the Manuscript Anne Donnet (b) Revising It for Intellectual Content Anne Donnet Category 3 (a) Final Approval of the Completed Manuscript Anne Donnet
REFERENCES 1. Sander D, Winbeck K, Etgen T, Knapp R, Klingelhöfer J, Conrad B. Disturbance of venous flow patterns in patients with transient global amnesia. Lancet. 2000;356:1982-1984. 2. Bartsch T, Deuschl G. Transient global amnesia: Functional anatomy and clinical implications. Lancet Neurol. 2010;9:205-214. 3. Caplan L, Chedru F, Lhermitte F, Mayman C. Transient global amnesia and migraine. Neurology. 1981;31:1167-1170. 4. Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 2nd edition. Cephalalgia. 2004;24(Suppl. 1):9-160. 5. Lanteri-Minet M, Autret A, Baudesson G, et al. French survey network on headaches and facial pains. In: Olesen J, ed. The Classification and Diagnosis of Headache Disorders. New York: Oxford University Press; 2005:287-293. 6. Hodges JR, Warlow CP. The aetiology of transient global amnesia. A case-control study of 114 cases with prospective follow-up. Brain. 1990;113 (Pt 3):639-657. 7. Rösler A, Mrass GJ, Frese A, Albert I, Schnorpfeil F. Precipitating factors of transient global amnesia. J Neurol. 1999;246:53-54.
June 2015 8. Lewis SL. Aetiology of transient global amnesia. Lancet. 1998;152:397-399. 9. Schreiber SJ, Doepp F, Klingebiel R, Valdueza JM. Internal jugular vein valve incompetence and intracranial venous anatomy in transient global amnesia. J Neurol Neurosurg Psychiatry. 2005;76: 509-513. 10. Chung CP, Hsu HY, Chao AC, Chang FC, Sheng WY, Hu HH. Detection of intracranial venous reflux in patients of transient global amnesia. Neurology. 2006;66:1873-1877. 11. Lantéri-Minet M, Valade D, Géraud G, Chautard MH, Lucas C. Migraine and probable migraineresults of FRAMIG 3, a French nationwide survey carried out according to the 2004 IHS classification. Cephalalgia. 2005;25:1146-1158. 12. Dalla Volta G, Zavarise P, Ngonga G, Premi E, Padovani A. Transient global amnesia as a presenting aura. Headache. 2014;54:551-552. 13. Olesen J, Jorgensen MB. Leao’s spreading depression in the hippocampus explains transient global amnesia. A hypothesis. Acta Neurol Scand. 1986;73:219-220. 14. Evans RW, Lewis SL. Transient global amnesia and migraine. Headache. 2005;45:1408-1410. 15. Schmidtke K, Ehmsen L. Transient global amnesia and migraine. A case control study. Eur Neurol. 1998;40:9-14. 16. Tosi L, Righetti CA. Transient global amnesia and migraine in young people. Clin Neurol Neurosurg. 1997;99:63-65. 17. Amit R, Shapira Y, Flusser H, Aker M. Basilar migraine manifesting as transient global amnesia in a 9-year-old child. Headache. 1986;26:17-18. 18. Sheth RD, Riggs JE, Bodensteiner JB. Acute confusional migraine: Variant of transient global amnesia. Pediatr Neurol. 1995;12:129-131. 19. Olivarius B, Jensen T. Transient global amnesia in migraine. Headache. 1979;19:335-338. 20. Gil-Martinez T, Galiano R. Transient global amnesia following the use of ergots in the treatment of migraine. Rev Neurol. 2004;39:929-931. 21. Pradalier A, Lutz G, Vincent D. Transient global amnesia, migraine, thalamic infarct, dihydroergotamine and sumatriptan. Headache. 2000;40:324327. 22. Fernandez A, Rincon F, Mazer SP, Elkind MS. Magnetic resonance imaging changes in a patient with
Headache
23.
24.
25.
26.
migraine attack and transient global amnesia after cardiac catheterization. CNS Spectr. 2005;10:980983. Montagna P, Cerullo A, Cortelli P. Transient global amnesia occurring as migraine aura. J Headache Pain. 2000;1:57-59. Dupuis M, Pierre P, Gonsette R. Transient global amnesia and migraine in twin sisters. J Neurol Neurosurg Psychiatry. 1987;50:816-824. Caffarra P, Scaglioni A, Malvezzi L, Manzoni GM. Transient global amnesia and migraine. Ital J Neurol Sci. 1988;9:287-289. Sacquegna T, Cortelli P, Baldrati A, de Carolis P, Tinuper P, Lugaresi E. Impairment of memory and consciousness in migraine: Clinical and EEG study. Funct Neurol. 1986;4:431-437.
859 27. Maggioni F, Mainardi F, Bellamio M, Zanchin G. Transient global amnesia triggered by migraine in monozygotic twins. Headache. 2011;51:1305-1308. 28. Crowell G, Stump D, Biller J, McHenry L, Toole J. The transient global amnesia-migraine connection. Arch Neurol. 1984;41:75-79. 29. Diener HC, Kurth T, Dodick D. Patent foramen ovale and migraine. Curr Pain Headache Rep. 2007;11:236-240. 30. Maalikjy. Akkawi N, Agosti C, Anzola GP, et al. Transient global amnesia: A clinical and sonographic study. Eur Neurol. 2003;49:67-71. 31. Klötzsch C, Sliwka U, Berlit P, Noth J. An increased frequency of patent foramen ovale in patients with transient global amnesia. Analysis of 53 consecutive patients. Arch Neurol. 1996;53:504-508.
Headache © 2015 American Headache Society
Brief Communications Transient Global Amnesia Triggered by Migraine in a French Tertiary-Care Center: An 11-Year Retrospective Analysis Anne Donnet, MD
Objective.—The etiology of transient global amnesia (TGA) remains unclear, and flow disturbances in the mesial temporal lobes secondary to venous congestion have been proposed as a potential cause. The occurrence of TGA during a migraine attack is a rare condition. Methods.—This 11-year retrospective study in one French center describes patients’ characteristics, type of migraine, investigations, treatment with vasoconstrictor during the TGA/migraine attack, and outcome in patients who had TGA during a migraine attack. Results.—Among 8821 new patients, 6 cases of TGA occurring during a migraine attack were identified. For a majority of patients, TGA occurs after the beginning of the attack. TGA always occurs during a severe migraine attack, with vomiting or vomiting efforts. Vomiting or vomiting efforts always precede a TGA episode. Conclusions.—TGA occurring during a migraine attack is rare. Since a Valsalva maneuver, such as forceful vomiting, is frequently described at the origin of the attack, blocking venous return through the superior venous cava may allow brief retrograde transmission of high venous pressure from the arms to the cerebral venous system, resulting in venous ischemia to the diencephalon or mesial temporal lobes and causing TGA. Key words: transient global amnesia, migraine, cortical spreading depression-migrainous aura (Headache 2015;55:853-859)
TGA have been widely discussed.2 TGA is classically associated with a past history of migraine with or without aura.3 Headaches may also occur during a TGA episode.3 However, the occurrence of TGA during a migraine attack is a rare condition. Six observations of TGA occurring during a migraine attack are presented and discussed.
Transient global amnesia (TGA) is the inability to retain new information and to recall past events during a period of minutes or hours. Its etiology is unclear, and flow disturbances in the mesial temporal lobes secondary to venous congestion have been proposed as a potential cause. Ultrasonographic evaluation of the internal jugular vein (IJV) has demonstrated valvular insufficiency in TGA.1 Pathophysiological mechanisms linking migraine and
Address all correspondence to A. Donnet, Centre d’Evaluation et de Traitement de la Douleur, Hôpital Timone, 264 Boulevard Saint-Pierre, 13385 Marseille Cedex 05, France.
METHODS AND CASE REPORTS Between October 2002 and June 2013, a total of 7725 new patients with diagnosis criteria of migraine without aura (MWoA) according to the second edition of the International Classification of Headache Disorders (ICHD-II)4 (code 1.1), and 1096 new patients with the ICHD-II diagnosis criteria of
Accepted for publication February 2, 2015.
Conflict of Interest: None.
From the Centre d’Evaluation et de Traitement de la Douleur, Hôpital Timone, Marseille, France (A. Donnet).
853
854 migraine with aura (MWA) (1.2.1) consulted in our center (Timone Hospital, Marseille). Six cases of TGA occurring during a migraine attack were identified among Marseille’s 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.5 The French 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. One neurologist reviewed the files of patients with known TGA occurring during a migraine attack. We used the criteria of TGA as defined by Hodges:6 pure loss of fixation memory, no impairment of alertness, self-identity, or other focal neurological involvement, ceasing within 12 hours, and associated with repetitive questioning and anxiety. New consulting patients diagnosed with TGA occurring during a migraine attack were also recruited. Frequency of migraine attacks was classified as lowfrequency migraine, which was defined as between 0 and 9 days of migraine per month for 3 months; highfrequency migraine, when there were between 10 and 14 days of migraine per month for 3 months; and chronic migraine and/or medication-overuse headache, when there were more than 15 days of headache per month for 3 months.
RESULTS Among the 8821 new patients consulting from October 2002 to June 2013 in our participating OMH center, we found 6 (6.8 TGA per 10,000 new patients) who were diagnosed with TGA occurring during a migraine attack. Patients’ characteristics are displayed in Table 1. Of these 6 patients, 5 were women. Median patient age at the time of TGA was 54.2 (44-66 years). Migraine Characteristics.—Five patients have a personal history of MWoA. One patient has both MWoA and MWA. TGA occurring during a migraine
June 2015 attack always occurred in patients with low-frequency migraine attacks. TGA always occurs during a severe migraine attack, with vomiting (5/6) or vomiting efforts (1/6). Vomiting or vomiting efforts always precede a TGA episode. Two patients had taken a vasoconstrictor (zolmitriptan or almotriptan) during the headache. TGA Characteristics.—All patients had TGA conforming to Hodges’ definition.6 All patients – except one – reported a triggering event: emotional stress (1), departure for a long trip (1), cold weather (snow) (1), beginning of the holidays (1), professional overwork (1). All patients had TGA in the presence of a witness, which allowed for reconstruction of the precise progress of the attack. Mean duration of TGA was 6 hours (4-8). All patients except one had experienced a single episode of TGA. Only one patient had TGA recurrences 11 and 12 years after the first episode. The second and third episodes of TGA occurred after the patient had been migraine-free for several years, and TGA was not accompanied or followed by headache. His brother also complained of recurrent TGA.
DISCUSSION TGA is defined by a sudden onset of anterograde and retrograde amnesia that lasts up to 24 hours. It is a rare event: epidemiological studies show that the incidence of TGA ranges between 3 and 8 per 100,000 people per year. Seventy-five percent of attacks occur in people between 50 and 70 years of age, and occurrence in patients younger than 40 years of age is rare.2 In most cases, TGA occurs once in a lifetime, and the same patient rarely presents another amnestic episode. The nature of precipitating events has been studied and Valsalva-associated maneuvers, emotional stress, or sudden contact with cold have been described.7 The underlying pathomechanism of TGA is still under discussion. Reversible diffusion-weighted imaging hyperintensities in the hippocampus have recently been found in magnetic resonance imaging (MRI) of patients with TGA during acute events. These focal lesions can be consistently detected in the CA1 field in the cornu ammonis.2 Proposed
MWoA since adolescence
MWoA since adolescence
MWoA since adolescence
MWoA since adolescence MWA (visual, paresthesic, and aphasic aura). Rare occurrence but very severe MWA
MWoA since adolescence
F/62
F/66
F/44
F/46 ans
F/62
TGA
2014 beginning with nausea, vomiting, pallor followed by TGA Severe headache after TGA Duration of TGA attack = 8 hours No precipitating factor
2010 MWA Visual, paresthesic, and aphasic aura followed by a severe headache with vomiting and TGA Duration of TGA attack = 5-6 hours Precipitating factor: beginning of the holidays
2002 Severe headache with vomiting followed by TGA Duration of TGA attack = 4 hours Precipitating factor: professional outwork
2001 Severe headache, nausea, vomiting effort followed by TGA Duration of TGA attack = 6-8 hours
2009 Severe headache with vomiting followed by TGA Duration of TGA = 5 hours Precipitating factor: departure for a long journey
1999 Severe headache with vomiting followed by TGA Duration of TGA = 7 hours Precipitating factor: cold weather (snow)
MWA = migraine with aura; MWoA = migraine without aura.
MWoA since adolescence Attacks were severe, with a frequency of 1 or 2 per week
Type of Migraine
M/55
Sex/Age at Time of TGA
Almotriptan during headache
Zolmitriptan during the headache
No
No
No
Treatment With Vasoconstrictor During the TGA/Migraine Attack
Table 1.—Patients’ Characteristics
CT scan and cerebral MRI
EEG-cerebral MRI (normal)
Cerebral MRI (normal)
CT scan and cerebral MRI
EEG, cerebral MRI (normal)
Lumbar puncture-EEG-cerebral MRI (normal)
Investigations
Rare MWoA attacks
No follow up since 2003
Last follow up 2011: MWoA attacks with a low frequency
MWoA 3 or 4 attacks per month
No migraine attack since 2003 Recurrence of TGA in 2010 and in 2012 without migraine attack
Outcome
Headache 855
856 mechanisms include hippocampal ischemic events, epilepsy, and migraine. Recently, the hypothesis that transient retrograde venous congestion and venous ischemia of temporobasal structures cause TGA has been suggested.1,8 Since a Valsalva maneuver is frequently described at the origin of the attack, the blocking of venous return through the superior venous cava may allow brief retrograde transmission of high venous pressure from the arms to the cerebral venous system; this results in venous ischemia in the diencephalon or mesial temporal lobes and in TGA.8 An incompetent jugular valve would make patients more susceptible to retrograde venous flow. In fact, a higher prevalence of IJV valve incompetence has been described in TGA patients,9 and retrograde intracranial venous flow caused by left brachiocephalic vein compression was demonstrated only in patients with TGA.10 However, its contributing role in TGA pathogenesis is still debated. Schreiber et al9 hypothesized that Valsalva maneuvers and venous outflow occur only as a cofactor, and that the underlying mechanism of TGA is probably multifactorial. On the other hand, migraine is a frequent disease. The current overall prevalence of migraine in France is estimated at 21.3% according to the IHS (International Headache Society) classification.11 Prevalence is highest in women, and in people between the ages of 25 and 55 years. Everything seemed to oppose these 2 diseases. Nonetheless, a comorbidity between TGA and migraine is suggested on large series of patients, suggesting a prevalence of migraine in TGA patients; the link between the two, however, needs to be clarified.2,3 Moreover, TGA and migraine share common precipitating factors.3 TGA has been considered as a migrainous aura12 (Table 2). Olesen et al12 hypothesized that TGA might occur as a consequence of cortical spreading depression (CSD) in the hippocampus. They suggest that the events that trigger TGA cause the release of glutamate in the hippocampi, triggering migrainous CSD and transient hippocampal dysfunction. CSD in the hippocampus might affect CA1 neuronal function, and induce cellular metabolic changes resulting in TGA.13 The usual age distribution of TGA, the triggering events that provoke it, and the recent MRI
June 2015 findings are arguments against migrainous CSD as the cause of TGA.14 A case control study argues against the hypothesis that TGA represents a type of migraine aura or migraine equivalent.15 However, current studies in CSD confirm that this phenomenon plays an important role in some neurologic disorders, including migraine, but also TGA, cerebrovascular disorders, and head injury. If MWoA is predominant in our study, the possible role of CSD cannot be excluded. TGA occurring during a migraine attack has been rarely reported (Table 2). Some observations in pediatric population are probably related to migrainous complex aura (basilar-type migraine16 or confusional migraine).17,18 TGA, after administration of vasoconstrictors for migraine treatment, is reported in 4 cases.19-21 One case of TGA associated with MWA during cardiac catheterization has been described.22 Besides these particular cases, 2 situations can be described. In the first, TGA occurs before the migraine attack and can be considered as a migrainous aura.23,24 This is an exceptional occurrence, with 4 cases reported in the literature (3 women and 1 man aged 38-70). Two patients have had MWA after the TGA; one patient had visual aura without migrainous headache after the TGA. On the other hand, TGA may occur after the beginning of the migraine attack.19,25-28 Our case reports have several specific points of interest. First, they confirm that TGA occurring during a migraine attack occurs, in a large majority of cases, after the beginning of the headache and during a severe attack. Second, 5 patients have MWoA exclusively, and in one it is associated with MWA and without aura. The existence of TGA after the beginning of the headache, and the predominance of MWoA between subjects are not in favor of the role of CSD. Third, the existence of vomiting or vomiting efforts is systematically described. A Valsalva maneuver seems to be the major precipitating factor for TGA due to the systematic presence of vomiting. Fourth, the role of patent foramen ovale (PFO) may be discussed. Epidemiological data suggest a bidirectional link between PFO and MWA with a
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Table 2.—Characteristics of Patients With Transient Global Amnesia Occurring During a Migraine Attack
TGA during the migraine
TGA before the migraine
Basilar-type or confusional migraine Ergotamine
Catheterization
Sex
Age
MWoA/MWA
M M M M
46 36 43 57
M
31
MWA MWA MWA MWA followed by TGA – recurrent episodes MWoA, MWA
F M
59 68
MWoA, MWA MWoA
M
60
MWoA
F
64
MWoA, MWA
M
38
MWoA, MWA
F
55
MWA
F
70
MWoA
M M F F F
9 16 13 13 54
Basilar-type migraine MWoA Basilar-type migraine Basilar-type migraine MWoA
F F F
65 63 58
MWoA MWoA MWoA before TGA
M
50
MWA
Comments
References
Caplan et al, 19813
Seven cases of TGA associated with headache MWoA attack followed by TGA Recurrent attacks of MWoA followed by TGA MWoA attack followed by TGA MWoA followed by TGA Recurrent attacks of MWoA followed by TGA MWoA followed by TGA Two episodes of TGA before MWoA Two attacks of TGA followed by immediate migraine without aura TGA immediately followed by visual aura without headache Recurrent episodes of transient global amnesia followed by intense headache
Crowell, 198428 Sacquegna et al, 198626 Caffara et al, 198825 Maggioni et al, 201127 Maggioni et al, 201127 Dupuis et al, 198724 Montagna et al, 200023 Montagna et al, 200023 Dalla Volta et al, 201412
? No headache ? ? ? MWoA before TGA Cerebral MRI: right thalamic infarct Vasoconstrictors as treatment of migraine (dihydroergotamine, sumatriptan) Ergotamine Dihydroergotamine Ergotamine
Amit et al, 198617 Tosi et al, 199716
MWA before TGA After catheterization Cerebral MRI: left temporal ischemic lesion
Fernandez et al, 200522
Tosi et al, 199716 Pradalier et al, 200021
Gil-Martinez et al, 200420 Olivarius et al, 197919
MWA = migraine with aura; MWoA = migraine without aura.
relative risk of 2 for PFO in subjects with MWA and for MWA in subjects with PFO. There is no evidence for a link between PFO and MWoA. This link is not systematic and applies only to subsets of PFO, mostly large ones. A coincidence of 2 conditions, however, does not necessarily imply a causal relationship.29 Results on the role of PFO in TGA are controversial.30,31 The existence of PFO has not been
researched in our patients. Finally, TGA may be the consequence of multiple pathophysiological mechanisms, rather than the result of a single cause. However, a Valsalva maneuver, such as vomiting, described at the origin of the attack, which allows brief retrograde transmission of high venous pressure to the cerebral venous system, seems to be the common initial symptom.
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STATEMENT OF AUTHORSHIP Category 1 (a) Conception and Design Anne Donnet (b) Acquisition of Data Anne Donnet (c) Analysis and Interpretation of Data Anne Donnet Category 2 (a) Drafting the Manuscript Anne Donnet (b) Revising It for Intellectual Content Anne Donnet Category 3 (a) Final Approval of the Completed Manuscript Anne Donnet
REFERENCES 1. Sander D, Winbeck K, Etgen T, Knapp R, Klingelhöfer J, Conrad B. Disturbance of venous flow patterns in patients with transient global amnesia. Lancet. 2000;356:1982-1984. 2. Bartsch T, Deuschl G. Transient global amnesia: Functional anatomy and clinical implications. Lancet Neurol. 2010;9:205-214. 3. Caplan L, Chedru F, Lhermitte F, Mayman C. Transient global amnesia and migraine. Neurology. 1981;31:1167-1170. 4. Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 2nd edition. Cephalalgia. 2004;24(Suppl. 1):9-160. 5. Lanteri-Minet M, Autret A, Baudesson G, et al. French survey network on headaches and facial pains. In: Olesen J, ed. The Classification and Diagnosis of Headache Disorders. New York: Oxford University Press; 2005:287-293. 6. Hodges JR, Warlow CP. The aetiology of transient global amnesia. A case-control study of 114 cases with prospective follow-up. Brain. 1990;113 (Pt 3):639-657. 7. Rösler A, Mrass GJ, Frese A, Albert I, Schnorpfeil F. Precipitating factors of transient global amnesia. J Neurol. 1999;246:53-54.
June 2015 8. Lewis SL. Aetiology of transient global amnesia. Lancet. 1998;152:397-399. 9. Schreiber SJ, Doepp F, Klingebiel R, Valdueza JM. Internal jugular vein valve incompetence and intracranial venous anatomy in transient global amnesia. J Neurol Neurosurg Psychiatry. 2005;76: 509-513. 10. Chung CP, Hsu HY, Chao AC, Chang FC, Sheng WY, Hu HH. Detection of intracranial venous reflux in patients of transient global amnesia. Neurology. 2006;66:1873-1877. 11. Lantéri-Minet M, Valade D, Géraud G, Chautard MH, Lucas C. Migraine and probable migraineresults of FRAMIG 3, a French nationwide survey carried out according to the 2004 IHS classification. Cephalalgia. 2005;25:1146-1158. 12. Dalla Volta G, Zavarise P, Ngonga G, Premi E, Padovani A. Transient global amnesia as a presenting aura. Headache. 2014;54:551-552. 13. Olesen J, Jorgensen MB. Leao’s spreading depression in the hippocampus explains transient global amnesia. A hypothesis. Acta Neurol Scand. 1986;73:219-220. 14. Evans RW, Lewis SL. Transient global amnesia and migraine. Headache. 2005;45:1408-1410. 15. Schmidtke K, Ehmsen L. Transient global amnesia and migraine. A case control study. Eur Neurol. 1998;40:9-14. 16. Tosi L, Righetti CA. Transient global amnesia and migraine in young people. Clin Neurol Neurosurg. 1997;99:63-65. 17. Amit R, Shapira Y, Flusser H, Aker M. Basilar migraine manifesting as transient global amnesia in a 9-year-old child. Headache. 1986;26:17-18. 18. Sheth RD, Riggs JE, Bodensteiner JB. Acute confusional migraine: Variant of transient global amnesia. Pediatr Neurol. 1995;12:129-131. 19. Olivarius B, Jensen T. Transient global amnesia in migraine. Headache. 1979;19:335-338. 20. Gil-Martinez T, Galiano R. Transient global amnesia following the use of ergots in the treatment of migraine. Rev Neurol. 2004;39:929-931. 21. Pradalier A, Lutz G, Vincent D. Transient global amnesia, migraine, thalamic infarct, dihydroergotamine and sumatriptan. Headache. 2000;40:324327. 22. Fernandez A, Rincon F, Mazer SP, Elkind MS. Magnetic resonance imaging changes in a patient with
Headache
23.
24.
25.
26.
migraine attack and transient global amnesia after cardiac catheterization. CNS Spectr. 2005;10:980983. Montagna P, Cerullo A, Cortelli P. Transient global amnesia occurring as migraine aura. J Headache Pain. 2000;1:57-59. Dupuis M, Pierre P, Gonsette R. Transient global amnesia and migraine in twin sisters. J Neurol Neurosurg Psychiatry. 1987;50:816-824. Caffarra P, Scaglioni A, Malvezzi L, Manzoni GM. Transient global amnesia and migraine. Ital J Neurol Sci. 1988;9:287-289. Sacquegna T, Cortelli P, Baldrati A, de Carolis P, Tinuper P, Lugaresi E. Impairment of memory and consciousness in migraine: Clinical and EEG study. Funct Neurol. 1986;4:431-437.
859 27. Maggioni F, Mainardi F, Bellamio M, Zanchin G. Transient global amnesia triggered by migraine in monozygotic twins. Headache. 2011;51:1305-1308. 28. Crowell G, Stump D, Biller J, McHenry L, Toole J. The transient global amnesia-migraine connection. Arch Neurol. 1984;41:75-79. 29. Diener HC, Kurth T, Dodick D. Patent foramen ovale and migraine. Curr Pain Headache Rep. 2007;11:236-240. 30. Maalikjy. Akkawi N, Agosti C, Anzola GP, et al. Transient global amnesia: A clinical and sonographic study. Eur Neurol. 2003;49:67-71. 31. Klötzsch C, Sliwka U, Berlit P, Noth J. An increased frequency of patent foramen ovale in patients with transient global amnesia. Analysis of 53 consecutive patients. Arch Neurol. 1996;53:504-508.
