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The Neural Basis of Cognition

ISSN: 1355-4794 (Print) 1465-3656 (Online) Journal homepage: http://www.tandfonline.com/loi/nncs20

Posterior hippocampal stroke presenting with
transient global amnesia
Federica Naldi, Simone Baiardi, Maria Guarino, Luca Spinardi, Fabio
Cirignotta & Andrea Stracciari
To cite this article: Federica Naldi, Simone Baiardi, Maria Guarino, Luca Spinardi, Fabio
Cirignotta & Andrea Stracciari (2016): Posterior hippocampal stroke presenting with transient
global amnesia, Neurocase, DOI: 10.1080/13554794.2016.1270329
To link to this article: http://dx.doi.org/10.1080/13554794.2016.1270329

Published online: 22 Dec 2016.

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Date: 27 December 2016, At: 05:29

NEUROCASE, 2016
http://dx.doi.org/10.1080/13554794.2016.1270329

Posterior hippocampal stroke presenting with transient global amnesia
Federica Naldia*, Simone Baiardia,b*, Maria Guarinoa, Luca Spinardic, Fabio Cirignottaa,b and Andrea Stracciaria
a

Neurology Unit, S. Orsola-Malpighi University Hospital, Bologna, Italy; bDepartment of Biomedical and Neuromotor Sciences, University of
Bologna, Bologna, Italy; cDiagnostic and Interventional Neuroradiology Unit, S. Orsola-Malpighi Hospital, Bologna, Italy
ABSTRACT

ARTICLE HISTORY

The acute onset of isolated amnesia is an intriguing challenge for neurologist, because the lack of
associated signs can be misleading for diagnosis. The most common cause is transient global amnesia
(TGA), a benign condition, but rarely it results from abuse of substance/alcohol or cerebrovascular
diseases. In the latter, the brain region involved is the hippocampus. We describe a patient with
presenting symptoms of TGA, but affected by an ischemic hippocampal stroke. The computed tomography angiography helped the etiologic diagnosis showing an hemodynamic stenosis of the posterior
P2P segment. Interestingly, neuropsychological features were consistent with those found in patients
suffering TGA.

Received 25 February 2016
Accepted 5 December 2016

Introduction
Transient global amnesia (TGA) is a clinical syndrome characterized by sudden onset of transient anterograde and retrograde amnesia of variable extension, without consciousness
impairment or other cognitive disturbances (Arena &
Rabinstein, 2015). Patients usually exhibit stereotyped behavior, such as asking the same question over and over again, in
the absence of consciousness disorders and remarkable neurological deficits. The symptoms resolve within 24 h and
recurrence is rare (Arena & Rabinstein, 2015).
The pathophysiology of TGA is still not completely understood and several etiological factors have been proposed
including vascular origin, epileptic or migrainous mechanisms,
venous congestion, and psychological disturbances, but
pathogenic hypotheses are still a matter of debate (Bartsch &
Deuschl, 2010). Moreover, the occurrence of TGA-like episodes
has been observed after the intake of several substances
(alcohol, benzodiazepines, marijuana) (Stracciari, Guarino,
Crespi, & Pazzaglia, 1999).
The diagnosis is still clinical, according to Caplan and
Hodges criteria (Caplan, 1985; Hodges & Warlow, 1990).
While isolated TGA is considered a benign syndrome, it
may be the presenting symptom of a serious underlying condition. Therefore, beyond an accurate clinical evaluation,
patients with TGA should undergo comprehensive diagnostic
testing including computed tomography (CT) of the brain and
electroencephalography in the emergency department setting. When the symptoms last more than 24 h and there are
no confirmatory tests, magnetic resonance imaging of the
brain with diffusion-weighted imaging (MRI-DWI) sequences,
oxygenation status, serum electrolytes, glucose, and a toxicology screen should be performed. A comprehensive cardiac
evaluation including electrocardiogram and echocardiography, lipid panel and vascular studies (magnetic resonance
CONTACT Simone Baiardi
simone.baiardi5@studio.unibo.it
*These authors contributed equally to the manuscript.
© 2016 Informa UK Limited, trading as Taylor & Francis Group

KEYWORDS

Stroke; hippocampus;
global transient amnesia;
neuropsychology;
neuroimaging

angiography, CT angiography, carotid duplex ultrasonography,
and transcranial Doppler ultrasonography) should be considered in patients with vascular risk factors.
Here we describe the case of a patient who clinically presented with an episode of typical TGA but with an unusual
duration (more than 24 h), which proved to be due to
ischemic stroke in the posterior hippocampus.

Case report
An 82-year-old female presented with acute onset of amnesia,
mild confusion, perplexity, perseveration, and disorientation in
space and time. She had a medical history relevant for hypertension and the concomitant medications were benazepril
(10 mg/day) and hydrochlorothiazide (12.5 mg/day).
At the time of first observation, 6 h after the onset of the
symptoms, her blood pressure was 170/80 mmHg and heart
rate was 85 bpm. Neurological examination revealed shortterm verbal memory impairment as well as a retrograde amnesia extending to the day prior to the initial onset of the
symptoms, without focal neurological signs or deficits. Her
daughter confirmed the absence of consciousness impairment
and excluded other cognitive disturbances other than amnesia. During the amnesic phase, an electroencephalogram was
unremarkable, particularly, epileptic abnormalities were ruled
out. Non-enhanced CT of the brain revealed hypo-density of
the right posterior hippocampus suggestive of acute ischemic
stroke. The diagnosis was confirmed by a subsequent brain
MRI, which displayed signal alteration involving the hippocampus and the para-hippocampal gyrus of the right hemisphere,
associated with signs of chronic vascular encephalopathy
(Figure 1(a,b)). The CT angiography documented a fetal origin
of right posterior cerebral artery (PCA) with a focal, hemodynamic stenosis of the posterior P2P segment (also known as
ambient segment) (Figure 1(c,d)).

2

F. NALDI ET AL.

Figure 1. Brain MRI displays signal hyperintensity of right hippocampus and para-hippocampus on Fluid Attenuated Inversion Recovery (a) and DWI (b) sequences
(see yellow arrows). A focal stenosis (about 3 mm) of the P2P segment of right posterior cerebral artery is documented by CT angiography [3-D (c) and Maximum
Intensity Projection (d) reconstruction; yellow arrows].

Discussion

The memory defect receded after 48 h and left a blank
for the acute episode. Neuropsychological assessment, performed 12 days after the disease onset, revealed only the
impairment in the delayed verbal memory recall at Rey
Auditory Verbal Learning Test (Table 1). Work-up investigating the embolic etiology of the event, which included electrocardiogram monitoring for occult atrial fibrillation and
echocardiography, was noncontributory. The patient was
discharged with an antiplatelet (acetylsalicylic acid
100 mg/day) and antihypertensive treatment, without residual neurological deficits. At the 1-month follow-up, the
patient was neurologically normal.

Ischemic stroke may rarely present with TGA. Cases of
“ischemic” TGA have been reported with lesions on the unilateral or bilateral hippocampus (Bhai, Biffi, Bakhadirov, &
Prasad, 2014; Carota, Lysandropoulos, & Calabrese, 2012;
Connelly, Chen, & Kwan, 2015; Kostić et al., 2015; Marinkovic,
Lyytinen, Valanne, Niinikuru, & Pekkonen, 2012; Nishiyori,
Nishida, Shioda, Suda, & Kato, 2014; Ott & Saver, 1993) and
less frequently in the splenium of the corpus callosum (Saito,
Rimura, Minematsu, Shiraishi, & Nakajima, 2003), in the fornix
(Gupta, Kantor, Tung, Zhang, & Albers, 2015), in the cingulate

Table 1. Neuropsychological assessment performed after 12 days from the disease onset. The only abnormal test involves the long-term verbal
memory recall (Rey Auditory Verbal Learning Test).
Test (range)
MMSE (0–30)
Attention
-Visual search (0–60)
-Stroop test: time in sec
-Errors
Verbal memory (Rey Auditory Verbal Learning Test)
-Immediate recall (0–75)
-Delayed recall (0–15)
Language
-Phonological words fluency (words beginning with F,A,S)
-Verbal semantic fluency
-Phrase construction (0–25)
Abstract reasoning
- Raven’s colored progressive matrices (1947) (0–36)
Visual spatial memory
-Immediate visual memory (0–22)
-Corsi’s blocks (0–9)
Praxis
- Copy of designs (0–12)
a

Raw score

Corrected scorea

Cutoff

Equivalent scoreb

27

26.3

25

–

48
27
0

53
12.25
–

31
36.92
4.24

4
4
4

28
1

38.1
4.3

28.53
4.69

3
0

36
36
14

41.7
42
18.2

17.35
25
8.72

4
4
2

23

27.1

18.96

3

16
4

17.9
4.5

13.85
3.75

2
3

12

–

7.18

4

Scores corrected for age, gender, and schooling.
Equivalent score classifies the performance on a five-point scale (range 0–4): 0 corresponds to a performance lower than the one-tailed tolerance
limit of population with 95% confidence interval and 4 to a score higher than the median value of the population, while scores 1–3 are
intermediate. MMSE - Mini-Mental State Examination.

b

NEUROCASE

gyrus (Gallardo-Tur, Romero-Godoy, de la Cruz Cosme, &
Arboix, 2014), or in the thalamic penetrating artery territory
(Ott & Saver, 1993). The involvement of hippocampal structures is simple to understand in relationship with its pivotal
role in memory processing. The prevalence of acute strokes
isolated to the hippocampus is 0.03% in a case series of 6,800
patients affected by ischemic stroke (Kumral, Deveci, Erdoğan,
& Enustun, 2015).
Because hippocampal vascular supply arise from the PCA, often
the hippocampus is involved in larger territorial strokes with clinical consequences derived from involvement of adjacent structures rather than from the hippocampus itself (Kumral et al.,
2015). Visual field deficits, weakness, confusion, and altered mental
status are common leading clinical signs of hippocampal stroke;
therefore, early phase phenotype is different compared to socalled pure or idiopathic TGA (Kumral et al., 2015; Szabo et al., 2009).
Lesions on the hippocampus could also be found in other
disease different from stroke, including epilepsy, limbic encephalitis, and, rarely, also in pure TGA. Because the lesion
neuroimaging pattern depends on etiology and there is a
high rate of false negative on early CT scans, especially when
trying to identify small areas of ischemia such as in the hippocampus (Adler, Warum, & Sapire, 2012; Pearce &
Bogousslavsky, 2009), brain MRI could help in the differential
diagnosis, when clinical diagnosis is challenging (Forster et al.,
2012).
In particular, the DWI sequences with apparent diffusion
coefficient mapping on MRI are useful in detection of small
ischemic lesions, when the brain changes are not visible in the
structural MRI (Enzinger et al., 2008; Holdstock, Mayes, Gong,
Roberts, & Kapur, 2005).
Several imaging studies in TGA patients using high-resolution
MRI, with optimized parameters, revealed focal, punctuate,
hyperintense 1–5-mm lesions of the lateral hippocampus on
DWI, in up to 85% of cases (Bartsch & Deuschl, 2010; Forster
et al., 2012). The detection of ischemic lesions on DWI is time
dependent, with maximum detection time frame within 48–72 h
after clinical onset and persistence for 7–10 days, but eventually
resolve (Bartsch, Alfke, Deuschl, and Jansen 2007; Scheel,
Malkowsky, Klingebiel, Schreiber, & Bohner, 2012).
Szabo (Szabo et al., 2009) in a series of 54 patients with PCA
territory stroke with hippocampal involvement recognized
four possible patterns of hippocampal ischemic lesions on
MRI-DWI: complete, lateral, dorsal, and small circumscribed
lesions in the lateral hippocampus, but a relationship between
topography and clinical presentation was not found. In all
cases described, however, additional ischemic lesions in the
posterior circulation were found and symptoms from lesions
outside the hippocampus were most common, whereas amnesic deficits were prominent in only one sixth of patients.
Kumral et al. (2015), who focused his research on isolated
hippocampal infarcts, described memory dysfunction in all
patients (n = 19), together with other manifestations according to the site of infarction, including altered consciousness,
visual hallucinations, dizziness, dullness, confusion, mood
states, and behavioral changes. None of the patients had
isolated memory deficits.
Our patient presented with clinical features of TGA as defined
by diagnostic criteria, except for the duration of symptoms

3

(more than 24 h). Neuropsychological features were consistent
with those found in patients suffering pure TGA (Gallassi et al.,
1993). A lesion in the right hippocampus and para-hippocampal
gyrus was detected early. Because of the duration of symptoms
(not typical of TGA) and abnormal findings on first brain CT scan,
MRI was performed to confirm an ischemic nature of the signal
alteration. The mechanism probably involved was a P2P focal
stenosis, ipsilateral to the hippocampal lesion. The cardiologic
clinical evaluation, the electrocardiogram monitoring for occult
atrial fibrillation, and echocardiography were unremarkable,
excluding an embolic source.
Usually patients with TGA have no evidence for an
increased rate of cerebrovascular risk factors (Enzinger et al.,
2008), such as in our case, and the “vascular hypothesis” of
TGA could not be stated for all cases.
This case, however, suggests that arterial ischemia could be
the etiopathogenetic mechanism underlying also of the pure
TGA phenotype. Considering the difficulty to make a precise
diagnosis within 24 h, arterial imaging in both typical and
quite atypical phenotypes could give important information
for the early management of patients, especially when an
ischemic etiology is confirmed.

Acknowledgment
The authors thank Cecilia Baroncini and Niamh Bernadette Casey who
edited the English text.

Disclosure statement
No potential conflict of interest was reported by the authors.

References
Adler, A. C., Warum, D., & Sapire, J. M. (2012). Transient global amnesia
caused by hippocampal infarct: Case report and review of literature.
Clinical Imaging, 36(5), 584–586. doi:10.1016/j.clinimag.2011.11.022
Arena, J. E., & Rabinstein, A. A. (2015). Transient global amnesia. Mayo
Clinic Proceedings, 90(2), 264–272. doi:10.1016/j.mayocp.2014.12.001
Bartsch, T., Alfke, K., Deuschl, G., & Jansen, O. (2007). Evolution of hippocampal CA-1 diffusion lesions in transient global amnesia. Annals of
Neurology, 62(5), 475–480. doi:10.1002/ana.21189
Bartsch, T., & Deuschl, G. (2010). Transient global amnesia: Functional
anatomy and clinical implications. The Lancet Neurology, 9(2), 205–
214. doi:10.1016/S1474-4422(09)70344-8
Bhai, S., Biffi, A., Bakhadirov, K., & Prasad, S. (2014). Complete anterograde
amnesia from simultaneous bilateral hippocampal infarction. The
Neurohospitalist, 4, 165–166. doi:10.1177/1941874414524795
Caplan, L. R. (1985). Transient global amnesia. In P. J. Vinken, G. W. Bruyn,
& H. Klawans (Eds.), Handbook of clinical neurology [revised series] (Vol.
1, pp. 205–218). Frederiks JAM, editors. Clinical neuropsychology.
Amsterdam: Elsevier Science.
Carota, A., Lysandropoulos, A. P., & Calabrese, P. J. (2012). Pure left
hippocampal stroke: A transient global amnesia-plus syndrome.
Journal of Neurology, 259(5), 989–992. doi:10.1007/s00415-011-6296-2
Connelly, K. L., Chen, X., & Kwan, P. F. (2015). Bilateral hippocampal stroke
secondary to acute cocaine intoxication. Oxford Medical Case Reports, 3
(3), 215–217. doi:10.1093/omcr/omv016
Enzinger, C., Thimary, F., Kapeller, P., Ropele, S., Schmidt, R., Ebner, F., &
Fazekas, F. (2008). Transient global amnesia: Diffusion-weighted imaging lesions and cerebrovascular disease. Stroke, 39(8), 2219–2225.
doi:10.1161/STROKEAHA.107.508655
Forster, A., Griebe, M., Gass, M., Kern, R., Hennerici, M. G., & Szabo, K.
(2012). Diffusion-weighted imaging for the differential diagnosis of

4

F. NALDI ET AL.

disorders affecting the hippocampus. Cerebrovascular Diseases, 33(2),
104–115. doi:10.1159/000332036
Gallardo-Tur, A., Romero-Godoy, J., de la Cruz Cosme, C., & Arboix, A.
(2014). Transient global amnesia associated with an acute infarction
at the cingulate gyrus. Case Reports in Neurological Medicine, 2014
(418180), 1–4. doi:10.1155/2014/418180
Gallassi, R., Stracciari, A., Morreale, A., Lorusso, S., Rebucci, G. G., &
Lugaresi, E. (1993). Transient global amnesia: Neuropsychological findings after single and multiple attacks. European Neurology, 33(4), 294–
298. doi:10.1159/000116957. Retrieved from http://www.ncbi.nlm.nih.
gov/pubmed
Gupta, M., Kantor, M. A., Tung, C. E., Zhang, N., & Albers, G. W. (2015).
Transient global amnesia associated with a unilateral infarction of the
fornix: Case report and review of the literature. Frontiers in Neurology, 5
(291), 1–4. doi:10.3389/fneur.2014.00291
Hodges, J. R., & Warlow, C. P. (1990). Syndromes of transient amnesia: Towards
a classification. A study of 153 cases. Journal of Neurology, Neurosurgery &
Psychiatry, 53(10), 834–843. doi:10.1136/jnnp.53.10.834 Retrieved from
http://jnnp.bmj.com
Holdstock, J. S., Mayes, A. R., Gong, Q. Y., Roberts, N., & Kapur, N. (2005).
Item recognition is less impaired than recall and associative recognition
in a patient with selective hippocampal damage. Hippocampus, 15(2),
203–215. doi:10.1002/(ISSN)1098-1063
Kostić, S., Pasovski, V., Krsmanović, Z., Bošković, Z., Kostić, D., Jovanovski,
A., & Jović-Stošić, J. (2015). Bilateral hippocampal infarction and amnesia: A case report. Vojnosanitetski Pregled, 72(6), 545–551. doi:10.2298/
VSP140330015K Retrieved from http://www.ncbi.nlm.nih.gov/pubmed
Kumral, E., Deveci, E. E., Erdoğan, C., & Enustun, C. (2015). Isolated
hippocampal infarcts: Vascular and neuropsychological findings.
Journal of the Neurological Sciences, 15(356), 83–89. doi:10.1016/j.
jns.2015.06.011

Marinkovic, I., Lyytinen, J., Valanne, L., Niinikuru, R., & Pekkonen, E. (2012).
Bilateral hippocampal infarction as etiology of sudden and prolonged
memory loss. Case Reports in Neurology, 4(3), 207–211. doi:10.1159/
000345564
Nishiyori, Y., Nishida, M., Shioda, K., Suda, S., & Kato, S. (2014). Unilateral
hippocampal infarction associated with an attempted suicide: A case
report. Journal of Medical Case Reports, 8, 219. doi:10.1186/1752-1947-8219
Ott, B. R., & Saver, J. L. (1993). Unilateral amnesic stroke. Six new cases and
a review of the literature. Stroke, 24(7), 1033–1042. doi:10.1161/01.
STR.24.7.1033
Pearce, J. M., & Bogousslavsky, J. (2009). ‘Les ictus amnésiques’ and transient global amnesia. European Neurologic, 62(3), 188–192. doi:10.1159/
000228263
Saito, K., Rimura, K., Minematsu, K., Shiraishi, A., & Nakajima, M. (2003).
Transient global amnesia associated with an acute infarction in the
retrosplenium of the corpus callosum. Journal of the
Neurological Sciences, 210(1–2), 95–97. doi:10.1016/S0022-510X(03)
00015-7
Scheel, M., Malkowsky, C., Klingebiel, R., Schreiber, S. J., & Bohner, G.
(2012). Magnetic resonance imaging in transient global amnesia:
Lessons learned from 198 cases. Clinical Neuroradiology, 22(4), 335–
340. doi:10.1007/s00062-012-0140-7
Stracciari, A., Guarino, M., Crespi, C., & Pazzaglia, P. (1999). Transient
amnesia triggered by acute marijuana intoxication. European Journal
of Neurology, 6(4), 521–523. doi:10.1046/j.1468-1331.1999.640521.x
Retrieved from http://www.ncbi.nlm.nih.gov/pubmed
Szabo, K., Forster, A., Jager, T., Kern, R., Griebe, M., Hennerici, M. G., & Gass,
A. (2009). Hippocampal lesion patterns in acute posterior cerebral
artery stroke: Clinical and MRI findings. Stroke, 40(6), 2042–2045.
doi:10.1161/STROKEAHA.108.536144