Journal of Neurology
https://doi.org/10.1007/s00415-019-09594-5

ORIGINAL COMMUNICATION

Concomitant reversible cerebral vasoconstriction syndrome
and transient global amnesia
Rosalie Boitet1 · Nicolas Gaillard1,5 · Eddine Bendiab1 · Lucas Corti1 · Caroline Roos2 · Jacques Reynes3 ·
Vincent Costalat4 · Caroline Arquizan1 · Anne Ducros1
Received: 6 August 2019 / Revised: 7 October 2019 / Accepted: 18 October 2019
© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Abstract
Background Reversible cerebral vasoconstriction syndrome (RCVS) is a common cause of thunderclap headache (TCH),
mainly recurrent, sometimes associated with seizures and/or neurological deficit. Association with amnesia is exceptional.
We report a case series of RCVS concomitant with transient global amnesia (TGA) and propose pathophysiologic hypotheses.
Methods We retrospectively reviewed clinical and radiological features of patients diagnosed with confirmed concomitant
RCVS and TGA between 2012 and 2018 in two specialized institutions.
Results Two women aged 67 and 53, and a 64-year-old man had a first thunderclap headache triggered by an acute emotional
stress, rapidly followed by TGA. Amnesia resolved within a few hours and RCVS was proven for all, with complete resolution of vasospasms within 3 months. All three patients had excellent outcome.
Conclusions RCVS and TGA can occur simultaneously, which suggests common mechanisms such as aberrant responses
to physical or emotional stress and cerebral vasoconstriction.
Keywords Thunderclap headache · Transient global amnesia · Vasospasm · Reversible cerebral vasoconstriction syndrome

Introduction
Reversible cerebral vasoconstriction syndrome (RCVS) is
characterized by severe headache, often thunderclap headaches (TCH), and reversible segmental constriction of the
cerebral arteries, with or without cortical subarachnoid
hemorrhage, infarction or intracerebral hemorrhage [1]. On
top of TCH, seizures and neurological deficit are commonly
observed [1]. Conversely, amnesia is exceptional. Transient
global amnesia (TGA) is defined by a sudden transient
* Nicolas Gaillard
n‑gaillard@chu‑montpellier.fr
1

Neurology Department, Montpellier University Hospital,
Montpellier, France

2

Emergency Headache Centre, Lariboisière Hospital,
Assistance Publique Des Hôpitaux de Paris, Paris, France

3

Infectious and Tropical Diseases Department, Montpellier
University Hospital, Montpellier, France

4

Department of Neuroradiology, Montpellier University
Hospital, Montpellier, France

5

Neurology Department, Hôpital Gui de Chauliac, 80 Avenue
Augustin Fliche, 34295 Montpellier, France

anterograde amnesia [2]. To our knowledge, co-occurrence
of RCVS and TGA has been described in two patients [3,
4]. We report the first series of three cases of RCVS with
TGA, implying a causal relationship between these two
pathologies.

Methods
We retrospectively reviewed clinical and radiological features of patients diagnosed with concomitant RCVS and
TGA between 2012 and 2018 in two specialized institutions. Confirmed RCVS was defined by (1) recent severe
headaches of sudden onset; (2) cerebral vasoconstriction
on computed-tomography angiography (CTA) or MRA or
TCD; (3) normalized arteries within 3 months. TGA was
defined as sudden, transient deficit of anterograde memory
without any other neurological impairment, in the absence
of another cause.
All patients agreed to participate to this observational
study, which was approved by the ethics committee.

13

Vol.:(0123456789)

Journal of Neurology

Results
Case 1
A 67-year-old woman, with a history of migraine with
aura and hypertension, had a thunderclap headache (TCH)
while feeling distressed during a trial. A few minutes later,
she developed typical anterograde amnesia in the presence
of witnesses that resolved within 3 h. Upon examination at
the local emergency department (ED), memory was normal, headache had disappeared, and diagnosis at discharge
was a TGA. On day 2, she relapsed with two episodes
of TCH, and returned to the ED. Non-contrast computed
tomography (CT) was normal. A fourth TCH recurred
while bending, and a fifth the next morning, during showering. She was admitted to the Lariboisière emergency
headache center. Blood pressure was 150/100 mmHg. During examination, she experienced a sixth TCH, followed
by a persistent throbbing pain. Cerebral CTA showed distal
vasospasms. Magnetic resonance imaging (MRI) showed a
tiny right temporal foci of restricted diffusion. Blood tests
and CSF analysis were normal. Nimodipine was started
and no new TCH occurred. On day 4, transcranial Doppler (TCD) disclosed increased peak systolic velocities on
the terminal right internal carotid artery and left anterior
cerebral artery (120 cm/s and 145 cm/s, respectively). One
month after onset, control TCD showed normalized flow
velocities.
One year later, she experienced a second TGA triggered by acute emotional stress (speaking out loud during
a ceremony), without any headache. A cerebral MRI was
performed, and was normal. There was no other relapse
for 6 years thereafter.

Case 2
A 53-year-old woman, without medical history, presented
a first TCH while she and her daughter were victims of a
sudden flood in their house. The patient took paracetamol,
and did not remember anything afterward. Upon arrival
to the ED in Montpellier, she had severe headaches with
vomiting, and anterograde amnesia without any other neurological deficit. Blood pressure was 180/90 mmHg. Noncontrast cerebral CT and blood tests were normal. Lumbar
puncture was subnormal (white cell count of 20/mm3).
Headache resolved within 3 h and amnesia within 6 h. She
had a second TCH during the evening, and a third on day
3, both lasting a few hours and followed by a moderate persistent headache. On day 3, CTA was normal. MRI showed
bilateral small diffusion-restricted hippocampal lesions
(Fig. 1a, b) and mild bilateral occipital hypersignals on

13

fluid-attenuated inversion recovery (FLAIR). On day 5,
cerebral MRI showed persistent temporal abnormalities,
multiple cortical subarachnoid FLAIR hypersignals, and
diffuse cerebral vasoconstriction on MRA (Fig. 1e, f).
Nimodipine was started without recurrence of significant
headache. On day 11, MRI showed complete resolution of
cerebral abnormalities (Fig. 1c, d, g–i). CTA at 3 months
showed normalized arteries (Fig. 1j, k).

Case 3
A 64-year-old man had a TCH while showering, just after
a sudden contrariety in the setting of physical activity on a
warm day. Then, he experienced amnesia for 40 min, during
which he remained alone in his bedroom, but dressed up and
prepared a bag, without remembering it. His wife witnessed
him just after he regained a normal memory. There was no
any clue to loss of consciousness. Severe headache lasted
all night long, and he presented to the ED in Montpellier
the day after. He had history of sleep apnea, dyslipidemia,
and used nasal decongestants three times a week. Physical
examination and standard biology were normal. Cerebral
CT with CTA was normal (Fig. 2d). MRI showed a small
right temporal diffusion-restricted lesion (Fig. 2a–c). He
was treated with low-dose aspirin and nimodipine. Constant headache with paroxysms persisted for 10 days then
decreased gradually to disappear on day 16. CTA on day 16
showed mild stenosis of a branch of the left posterior cerebral artery (Fig. 2e). Cerebral MRI at 1 month was normal.
CTA at 3 months showed normal arteries (Fig. 2f). While
vasospasm was seen only in one artery, association of severe
headache during 10 days and reversible cerebral vasospasm
made the diagnosis of RCVS.
Because of clinical and imaging course, the three patients
were diagnosed with RCVS and concomitant TGA, associated with a posterior reversible encephalopathy syndrome
in case 2.

Discussion
RCVS and TGA are two acute and reversible neurological
conditions, whose exact pathological mechanisms are still
unknown. In 2017, a case of TGA accompanying proven
RCVS was reported in a 65-year-old man who used reserpine
2 weeks before onset [3]. In 2019, a second case has been
described [4]. Herein, we report three more cases of TGA
with RCVS, suggesting this association is not fortuitous.
While RCVS predominates in females and peaks around
45 years [1], TGA equally affects both genders and peaks
between 50 and 70 years [2, 5]. In our series, there were two
women and one man, all of them within typical age range
of TGA.

Journal of Neurology

Fig. 1  Brain MRI (a, b) at day 5 showed bilateral temporal foci of
restricted diffusion and corresponding diminished apparent diffusion
coefficient. Temporal abnormalities have normalized on MRI (c, d) at
day 11. Axial FLAIR (e, f) at day 5 disclosed multiple cortical subarachnoid hypersignals. These multiple cortical subarachnoid hyper-

signals had disappeared on day 11 (g, h). MR angiography (i) at day
5 showed segmental vasoconstriction of proximal anterior and right
middle cerebral arteries (arrowheads). Computed tomography angiography (j, k) at 3 months disclosed normal cerebral arteries

RCVS is attributed to a transient deregulation of cerebral arterial tone [1]. Hypothetic mechanisms of transient
hippocampal hypoxia in TGA involve venous congestion,
spreading depression or transient ischemia [2, 4, 6]. TGA
is associated with transient foci of restricted MRI diffusion
of the hippocampal CA1 regions, which are highly vulnerable to hypoxia, in 0 to 84% of the cases [2, 6]. These variables figures may reflect an incomplete sensitivity of MRI
for punctate hypersignal foci on diffusion-weighted imaging (DWI), potentially due to differences in timing of MRI
acquisition, resolution of DWI sequences, thickness of MRI
slices, and mono- versus multiplanar acquisition, as already
described in MRI studies of small infarcts or TIA [6].
Headache is the most common symptom associated with
TGA (up to 40%) but usually has unspecific features, not
consistent with TCH [2]. In our three patients and in the

case reported by Kamm et al. [4], TCH was the presenting
manifestation of RCVS, and was accompanied or followed
within minutes by TGA. The patient described by Isahaya
et al. [3] presented with TGA and concomitant non-TCH
headache, then had TCH and neurological deficit a few
days later, and was diagnosed with RCVS. In addition, this
patient had a history of TGA without headache 15 years
before, suggesting TGA can recur with or without RCVS in
some patients. Moreover, 50 to 90% of TGA are provoked
by various triggers including strenuous physical exertion,
emotional stress, sudden immersion in cold or hot water,
pain, medical procedures, sexual intercourse, or Valsalva
maneuvers [2, 5]. Notably, exactly the same triggers provoke
80% of the TCH in RCVS [1]. High altitude has also been
reported as a trigger for both RCVS [7], and high-altitude
global amnesia, a condition similar to TGA [8]. In 2016, the

13

Journal of Neurology

Fig. 2  Right temporal foci of restricted diffusion (a) and corresponding diminished apparent diffusion coefficient (b), not visible on
FLAIR (c), are shown on MRI at day 1. Computed tomography angiography (d) at day 1 showed a normal left posterior cerebral artery

(arrow). Computed tomography angiography (e) at day 16 disclosed
vasoconstriction of the P2 segment of the left posterior cerebral
artery (arrow). Computed tomography angiography (f) at 3 months
showed normalization of the left posterior cerebral artery

striking similarities of triggers of RCVS and TGA have been
highlighted, suggesting that emotional and physical stress
might cause acute neuronal or vascular dysfunction through
sympathetic overactivity [9]. The concomitant occurrence
of both conditions further strengthens this hypothesis. All
our patients reported that an emotional stress preceded the
onset of TGA and RCVS. The excruciating pain of TCH
might also have contributed to provoke TGA.
Another condition with similarities to RCVS and TGA
is takotsubo stress cardiomyopathy (TKC) [10], which predominates in females aged 65–70 years. Emotional and
physical triggers, which predominate in women and men,
respectively, provoke more than two-thirds of TKC. One
case of RCVS and TKC occurring successively has been
reported [11]. Four women with concomitant TGA and TKC
have been described [12–15]. Finally, the patient with RCVS
and TGA reported by Kamm et al. had a history of TKC 5
years earlier [4].
Cases with TGA concomitant to RCVS or TKC may represent a rare association affecting only a minority of susceptible patients. Conversely, patients affected by a combination
of TGA, TKC and/or RCVS may have been underreported,
because recognition of thunderclap headache might be

hampered by transient amnesia in the setting of TGA, cerebral angiogram is not systematic in patients presenting with
either TGA or TKC, and cardiac investigations are not systematic in patients presenting with either RCVS or TGA.
Common triggers as well as overlapping occurrence of
TGA, RCVS and TKC strongly suggest common mechanisms. In some susceptible persons with or without predisposing factors such as vasoactive drug intake, migraine, or
anxiety, an acute emotional or physical stress may trigger a
wave of sympathetic overactivity leading to an abrupt and
sustained arteriolar and microvascular constriction with subsequent ischemic or hypoxic injury leading either to TGA
with DWI hypersignals in vulnerable hippocampal tissue, to
thunderclap headache and RVCS, when cerebral vasculature
is involved, and to TKC when cardiac microarterial vasoconstriction is affected [4, 9, 10, 15].
Given that some patients can develop any combination
of RCVS, TGA and TKC simultaneously or in succession,
we suggest that clinicians facing patients with TGA should
carefully check for the presence of associated thunderclap
headache and chest pain to promptly identify associated
RCVS and TKC, respectively. Conversely, thunderclap headache associated with anterograde amnesia should bring up

13

Journal of Neurology

a possible RCVS. Large studies of patients presenting with
one of the three conditions with detailed assessment of headache, memory and cardiac symptoms, as well as systematic
cerebral angiography, cerebral MRI with DWI sequences,
and cardiac echography would be necessary to determine the
degree of overlap between them. Further work is needed to
elucidate the exact biological mechanisms underlying relationship between these disorders.
Acknowledgements We acknowledge all the patients for their agreement to participate in this observational study.

Compliance with ethical standards
Conflicts of interest Nothing to report.
Ethical standards All patients agreed to participate to this observational study, which was approved by the local ethics committee.

References
1. Ducros A (2012) Reversible cerebral vasoconstriction syndrome.
Lancet Neurol 11(10):906–917
2. Bartsch T, Deuschl G (2010) Transient global amnesia: functional
anatomy and clinical implications. Lancet Neurol 9(2):205–214
3. Isahaya K, Shinohara K, Akamatu M, Shimizu T, Sakurai K,
Shiraishi M et al (2017) Reversible cerebral vasoconstriction
syndrome presenting with transient global amnesia. Intern Med
Tokyo Jpn 56(12):1569–1573
4. Kamm K, Schöberl F, Grabova D, Straube A, Zwergal A (2019)
RCVS and TGA: a common pathophysiology? J Neurol. https​://
doi.org/10.1007/s0041​5-019-09495​-7

5. Quinette P, Guillery-Girard B, Dayan J, de la Sayette V, Marquis
S, Viader F et al (2006) What does transient global amnesia really
mean? Review of the literature and thorough study of 142 cases.
Brain J Neurol 129(Pt 7):1640–1658
6. Scheel M, Malkowsky C, Klingebiel R et al (2012) Magnetic resonance imaging in transient global amnesia: lessons learned from
198 cases. Clin Neuroradiol 22:335
7. Neil WP, Dechant V, Urtecho J (2011) Pearls & oysters: reversible
cerebral vasoconstriction syndrome precipitated by ascent to high
altitude. Neurology 76(2):e7–e9
8. Litch JA, Bishop RA (2000) High-altitude global amnesia. Wilderness Environ Med 11(1):25–28
9. Ducros A, Wolff V (2016) The typical thunderclap headache of
reversible cerebral vasoconstriction syndrome and its various triggers. Headache 56(4):657–673
10. Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M et al (2015) Clinical features and outcomes of takotsubo (stress) cardiomyopathy. N Engl J Med 373(10):929–938
11. Canaple S, Fournier A, Bugnicourt J-M, Deramond H, Lamy C,
Godefroy O (2014) Reversible cerebral vasoconstriction syndrome
and tako-tsubo cardiomyopathy: an incidental association? Pratique Neurologique FMC 5(3):223–228
12. Kaida T, Nakano H, Watanabe I, Nishinari M, Yasuno N, Kubo
T et al (2009) A unique case of Takotsubo cardiomyopathy with
transient global amnesia which might be caused by simultaneous
and multiple vasospasm. J Card Fail 15(7):S159
13. Bobinger T, Köhrmann M, Raaz-Schrauder D, Schwab S,
Kallmünzer B (2013) Lost memories can break your heart: a case
report of transient global amnesia followed by takotsubo cardiomyopathy. Clin Res Cardiol 102(9):693–696
14. Sajeev J, Koshy A, Rajakariar K, Gordon G (2017) Takotsubo
cardiomyopathy and transient global amnesia: a shared aetiology.
BMJ Case Rep. https​://doi.org/10.1136/bcr-2017-21947​2
15. Pyle LM, Laghari FJ, Kinem DJ (2018) Concomitant transient
global amnesia and takotsubo cardiomyopathy following a stressful event. Clin Auton Res 28(6):597–598. https:​ //doi.org/10.1007/
s1028​6-018-0554-7

13