| Accepted: 15 June 2018

DOI: 10.1002/brb3.1078

ORIGINAL RESEARCH

Transient topographical disorientation due to right-sided
hippocampal hemorrhage
Stephanie Irving1,2 | Cauchy Pradhan1 | Marianne Dieterich1,2,3,4 | Thomas Brandt1,2,5 |
Andreas Zwergal1,3*

| Florian Schöberl1,3*

1
German Center for Vertigo and Balance
Disorders, DSGZ, Ludwig-MaximiliansUniversity, Munich, Germany
2

Abstract
Introduction: Topographical disorientation is defined as the inability to recognize

Graduate School of Systemic Neuroscience
(GSN), Ludwig-Maximilians-University,
Munich, Germany

familiar or unfamiliar environments. While its slowly progressive development is a

3

presentations are less frequent and mostly caused by strategic lesions within the

Department of Neurology, LudwigMaximilians-University, Munich, Germany
4

common feature of neurodegenerative processes like Alzheimer’s dementia, acute
cerebral navigation network. Depending on the lesion site, topographical

Munich Cluster of Systems Neurology,
SyNergy, Munich, Germany

disorientation can originate from deficits in landmark recognition and utilization for

5

route planning (egocentric navigation deficit), or disturbance of an overarching

Clinical Neurosciences, Ludwig-MaximiliansUniversity, Munich, Germany

Correspondence
Andreas Zwergal, Department of Neurology
and German Center for Vertigo and Balance
Disorders, DSGZ, Ludwig-MaximiliansUniversity, University Hospital Munich,
Marchioninistr. 15, Munich D-81377,
Germany.
Email: [email-masked]
Funding information
The study was performed as a project of
the German Center for Vertigo and Balance
Disorders (DSGZ) (grant number 01 EO
0901) with support of the German Federal
Ministry of Education and Health (BMBF)
and the Hertie Foundation (to TB).

cognitive map of the spatial environment (allocentric navigation deficit). However,
objective measurements of spatial navigation performance over time are largely
missing in patients with topographical disorientation.
Methods: We here report a 55-year-old patient with acute topographical
disorientation as the single symptom of right-sided hippocampal hemorrhage and
present quantitative gaze-monitoring head camera-based analyses of his path-finding
strategy and visual exploration behavior in a real space navigation paradigm.
Results: The patient exhibited severe allocentric and also egocentric navigation
deficits during the acute phase, shown by higher error rates at finding target items. In
addition, he showed a more extensive use of search saccades toward, and fixations
on, landmarks that could potentially serve as spatial cues. These deficits had been
completely compensated for after four months, when the patient performed
unremarkably in the real space navigation task, and used even more strongly
allocentric path optimization strategies than age-matched controls.
Conclusions: This case report highlights the integral function and right-sided
dominance of the hippocampal formation in the cerebral navigation network in
humans. It shows that the cognitive map can be restored completely despite a
residual hippocampal lesion, which illustrates the enormous plasticity of the cerebral
navigation network in humans.
KEYWORDS

hemorrhage, hippocampus, navigation, stroke, topographical disorientation

*These authors contributed equally to the manuscript.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.
Brain and Behavior. 2018;8:e01078.
https://doi.org/10.1002/brb3.1078

wileyonlinelibrary.com/journal/brb3

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1 | I NTRO D U C TI O N

IRVING et al.

phenomena or deficits of left/right recognition. MRI revealed an
acute focal hemorrhage, affecting the medial-posterior hippocampus

Previous studies show self-reported deficits of navigation abil-

and adjacent parahippocampus (Figure 1). Detailed neuropsycholog-

ities in about one-t hird of patients with mild stroke. However,

ical assessment was performed using the CERAD-plus test battery.

isolated topographical disorientation is an uncommonly reported

Performance in the subtests word list learning total, word list trial 1,

chief complaint of acute cerebral lesions characterized by sud-

2 and 3, word list delayed recall, word list recognition, figure draw-

den deficits in the recognition of familiar surroundings (Aguirre

ing, figure drawing recall and trail making test B was compared to

& D′Esposito, 1999; Van der Ham, Kant, Postma, & Visser-M eily,

age-matched controls using z-scores. H.W. furthermore underwent

2013). Lesions to various brain regions including critical hubs of

CLOX1 and CLOX2 tests to identify potential executive or visuo-

the cerebral navigation network may result in this impairment

spatial/visuoconstructive deficits. To exclude (hemi)neglect the Line

(Claessen & van der Ham, 2017; Ekstrom, Arnold, & Iaria, 2014).

Bisection and Balloons Test were performed. Results were depicted

Most often the right hippocampus or parahippocampus is in-

as deviation from the true center of lines for the Line Bisection Test

volved. It has been proposed that topographical disorientation

and total B Score and Laterality B Index for the Balloons Test. Upon

can originate from deficits in allocentric and/or egocentric spatial

informed written consent by the patient and approval by the Ethics

strategies (Claessen & van der Ham, 2017). The cognitive map the-

Committee of the Ludwig-Maximilians-University, Munich, topo-

ory posits that the right hippocampus mainly supports allocentric

graphical orientation was further assessed by an item search task

processing of space and is thus activated in more complex navi-

in an unfamiliar real space environment. The environment, in which

gational situations (Burgess, Maguire, & O’Keefe, 2002; O’Keefe

five items were placed as target points, was shown to the patient

& Nadel, 1978). In contrast, egocentric navigation mainly relies

first by an investigator-guided walk (exploration). Afterward, H.W.

on sequential distance and direction computations by means of

had to find the items in a pseudorandomized order within 10 min

landmark recognition and utilization, processed particularly in the

(navigation). The first part of the navigation paradigm was similar to

parahippocampal and retrosplenial cortex (Epstein & Vass, 2013).

the previous exploration route, which can be successfully solved by

In this case study, we report a spatially disoriented patient with

pure egocentric repetition of the route learned (i.e., sequential com-

an acute focal right-sided hippocampal/parahippocampal hem-

putations of distance and direction), thus requiring no cognitive map

orrhage, and the long-term time-course of his deficits as doc-

of the spatial environment. However, in the second part, the order

umented by quantitative analyses of path-f inding strategy and

of the target items was pseudorandomized, which consequently

gaze behavior in a real space environment. We hypothesized that

required detailed imagery of the environment as a whole and con-

(a) allo-  and egocentric navigation abilities would be impaired in

crete planning of novel routes, potentially including short-cuts (i.e., a

the acute stage due to the anatomic localization of the lesion and

cognitive map-based or allocentric strategy) (Figure 2). Patient H.W.

(b) navigation deficits would compensate over time by plasticity

wore a gaze-monitoring head camera throughout the experiment to

mechanisms within the cerebral navigation network.

document his visual exploration and head position (Schneider et al.,

The 55-year-old patient H.W. presented to the emergency room

2009). To quantify spatial navigation performance, the error rate for

after feeling a sudden loss of familiarity with the entire surround-

items approached during the navigation phase was calculated by

ing environment while he was driving home from work. He reported

offline analysis of the videos recorded by the gaze-monitoring head

no further subjective deficits, and in particular no amnesia, aphasia,

camera. Error rates were further separately analyzed for egocentric

apraxia or visual deficits. The neurological status was unremark-

and allocentric routes to test for specific deficits of either naviga-

able except for a severe spatial orientation deficit. In particular, we

tion strategy. Error rates were compared to those of an age-matched

could not find any signs of visual field deficits, neglect/extinction

cohort of 10 healthy men (age: 54.3 ± 6.2 years). The search path

F I G U R E 1 Lesion localization in a case of acute topographical disorientation. A T2 MRI sequence showed a focal hemorrhage in the right
hippocampus and parahippocampus (left side). The lesion in full-scale (red sphere) was projected to a standard T1 brain template (middle)
and a hippocampus (blue) and parahippocampus (green) 3D model (right side) to visualize the exact lesion localization. R: right, L: left, A:
anterior, P: posterior

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IRVING et al.

F I G U R E 2 Navigation paradigm in
real space. First row: exploration route
with a defined sequence of items. Second
row: In the first part of the navigation
paradigm, routes were tested which were
identical to the previous exploration route
(so-called egocentric routes). Third and
fourth row: in the second part, the order
of target items was changed in a way that
required the planning of novel routes
(so-called allocentric routes). Potential
short-cuts within the allocentric route
were recorded (fourth row, right side).
The sequence of the target items during
exploration and navigation is depicted
in a table and appears as corresponding
numbers besides the target items in the
figures

during the navigation task was mapped by accumulating time spent

The respective z-scores of subtest performance compared to age-

at a specific place and analyzed quantitatively (mean gait speed

matched controls were as follows: word list learning total: 0.49; word

during exploration or navigation, use of short-cuts, and time spent

list trial 1: 0.5, word list trial 2: 0.68; word list trial 3: −0.03; word list

at crossings). Video analysis allowed all fixation targets to be catego-

delayed recall: −0.09; word list recognition: 0.79; figure drawing: 0.7;

rized into fixed objects in space, mobile objects, and unspecific, non-

figure drawing recall: −1.27; trail making test B: −0.76. The patient

object fixations (e.g., the ground, wall, ceiling). The total number of

also showed a completely unremarkable performance on CLOX1/2

objects viewed and the number of unique objects viewed were also

tests (15/15 points each). Neglect was ruled out by formally estab-

recorded. The objects, which were fixated most frequently, were

lished tests such as the Line Bisection Test (deviation from true cen-

plotted on a ground map to indicate the visual exploration strategy

ter of lines: 0.5 ± 1.1 mm) and Balloons Test (total B Score of 20 and

and landmark use. Analysis was carried out as described previously

Laterality B Index of 100%).

(Stuart et al., 2014; Zwergal et al., 2016). The total number of sac-

On Day 2 after symptom onset, H.W.’s spatial navigation perfor-

cades and the saccade frequency were computed. Saccades directed

mance was severely impaired compared to that of an age-matched

to objects that were feasible as landmarks were defined as search

control cohort: he had a higher error rate on both egocentric routes (pa-

saccades. The total number of fixations, fixation frequency, and du-

tient: 100%, healthy controls: 5.0 ± 10.5%; t(9) = −28.500, p < 0.001)

ration were analyzed quantitatively. Fixation on a potential landmark

and allocentric routes (patient: 25%, healthy controls: 1.4 ± 4.5%;

was termed a search fixation. X and y gaze magnitudes and direction

t(9) = −15.500, p < 0.001), stayed longer at crossroads (t(9) = 4.118,

corresponding to the peak saccadic velocities and median fixation

p = 0.003) and “neglected” half of the spatial environment (Figure 3a).

periods were identified and displayed as wind rose plots (direction

Recognition of landmarks was impaired and fixations to objects were

and frequency of each class). All eye movement parameters were

nonsystematic in the patient, while healthy controls had a high con-

compared to data from the healthy controls.

sistency in retrieval of strategically important landmarks (Figure 3b).

Detailed neuropsychological assessment with the CERAD-

The plot of H.W.’s visual fixations in space and the heat map of eye

plus test battery indicated normal performance on all subtests.

displacement from straight ahead position showed a pattern that was

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F I G U R E 3 Navigational performance and visual exploration in the acute stage of topographical disorientation and during follow-up after
4 months. (a) Navigograms of the patient were constructed by plotting the search path onto the floor map, with x and y indicating position in
space and z accumulated time at place. The spatial position of the five search items (ball, mushroom, flower, train, house) is indicated on the
left. During the acute stage of topographical disorientation the navigogram showed a severely impaired navigational strategy with complete
loss of an internal cognitive map of the spatial environment. In the follow-up examination 4 months later, the navigational performance was
completely normal; the search path indicated an overall allocentric spatial strategy and was comparable to the group of healthy controls.
(b) During guided exploration, the patient (I) and healthy controls (II) showed a similar pattern of object fixations. However, during navigation
in the acute stage of topographical disorientation, the patient was not able to recognize these potential landmarks (III), whereas healthy
controls showed a high consistency of retrieval of known objects (V). In follow-up testing, the visual fixation pattern of H.W. normalized (IV)
and got more similar to the strategy of healthy controls. Green circles indicate the most frequently fixated objects with position in space
indicated on a ground map and diameters being relative to the total duration of fixation

F I G U R E 4 Visual exploration behavior in the acute stage of topographical disorientation and during follow-up after 4 months and
in healthy controls. Visual exploration behavior during navigation showed that saccadic eye movements during the acute stage of
topographical disorientation were mainly directed to the lateral position (left panel) and there were more exploratory saccades. During
follow-up, saccadic eye movements were distributed more equally along the horizontal and vertical axes (middle panel). In healthy controls,
saccades were directed mainly toward the ground and straight ahead (right panel)

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IRVING et al.

symmetric with respect to the lateral gaze position. This indicates that

1996; Epstein & Kanwisher, 1998). The pathological changes in

there was no visual neglect or asymmetric visual exploration behav-

gaze behavior and spatial navigation abilities in our patient resem-

ior, but instead, that visual awareness was comparable across both

bled the pattern of other hippocampal navigation disorders such

visual hemifields (Supporting information Figure S1). The apparent

as MCI-p atients (unpublished data). Functional compensation of

asymmetry of navigation path trajectory likely resulted from the lack

topographical disorientation in H.W. was rapid and complete, as

of any internal cognitive map of the surrounding environment and

reported in similar previous cases (Gil-N éciga et al., 2002; Rivest,

the distribution of visual cues/landmarks within it. However, given

Svoboda, McCarthy, & Moscovitch, 2018). The complete recov-

the restrictions of neuropsychological testing in the acute stage, the

ery of an allocentric navigation strategy despite a residual hippo-

possibility of basic spatial working memory problems could not defi-

campal lesion in follow-up MRI illustrates the great plasticity of

nitely be excluded. The patient chose the wrong turn at the beginning

the human navigation network (Byrne et al., 2007; Ekstrom et al.,

of the paradigm and from then just strayed up and down one hallway,

2014). In the follow-up assessment, the patient utilized an allocen-

unaware that there was another hallway parallel which he could ex-

tric strategy with successful use of short-cuts. Although it can-

plore. During navigation, he used more search saccades (t(9) = 3.613,

not be completely excluded that previous knowledge about the

p = 0.005) and tended to make more fixations to possible landmarks

room representation alleviated the paradigm the second time, the

(t(9) = 2.085, p = 0.067). His gaze behavior was predominantly ori-

most likely explanation may be a recruitment of extrahippocampal

ented within the horizontal plane (Figure 4, left). After an intense

network structures as has been described earlier for hippocam-

work-up of possible bleeding etiologies, the patient was discharged

pal lesions (Kolarik, Baer, Shahlaie, Yonelinas, & Ekstrom, 2018;

and followed up four months later.

Maguire, Nannery, & Spiers, 2006).

At that time, he reported no more problems with spatial ori-

In conclusion, acute topographical disorientation should be

entation in his daily life. Therefore, H.W. performed the same

recognized in clinical practice as a distinct and focal symptom

real space navigation task like during the acute stage without any

indicating right-sided lesions of the hippocampal formation. The

errors (egocentric routes t(9) = 1.500, p = 0.168 and allocentric

exceptional aspects of this case are the differentiation between

routes t(9) = 1.000, p = 0.343), used even more short-cuts than age-

egocentric and allocentric navigation strategies, the altered visual

matched controls (patient: 100%, healthy controls: 40.0 ± 46.07%;

exploration behavior without any other signs for (hemi)neglect or

t(9) = −3.417, p = 0.008) and incorporated all possible paths into

any asymmetric visual exploration in general. Importantly, isolated

his navigational trajectory, thus highly indicative for the presence

and severe topographical disorientation due to a very strategic le-

of an internal cognitive map of the spatial environment similar to

sion as in our case can recover rapidly and completely without any

healthy controls (Figure 3a). Landmark location and retrieval were

sequelae. It can only be speculated how plasticity supported the

similar to healthy controls (Figure 3b). Gaze behavior had also nor-

recovery of topographical orientation—either through a functional

malized, showing a more equal distribution of the vertical and hor-

substitution by the intact left hippocampus, or a fundamental re-

izontal planes (Figure 4, right). The numbers of search saccades

organization within the broader human spatial navigation network

(t(9) = 0.813, p = 0.437) and search fixations (t(9) = 1.179, p = 0.269)

including extrahippocampal hubs such as the retrosplenial and

were comparable to that of age-matched controls.

posterior parietal cortex.

Combining behavioral measurements of navigational and neuropsychological performance, we here present evidence that a
small, but strategic right-sided hippocampal/parahippocampal

AC K N OW LE D G M E NT S

lesion can cause acute topographical disorientation as a single
symptom and can lead to severe deficits of both allo-  and egocentric navigation strategies. This is remarkable as multiple brain
areas form a distributed cerebral network for spatial navigation

The authors thank Judy Benson and Paul Taylor for copy-editing the
manuscript.

in humans (Ekstrom et al., 2014; Epstein & Vass, 2013; Grön,
Wunderlich, Spitzer, Tomczak, & Riepe, 2000). This case underlines the integral function of the right hippocampus and parahippocampus within this network (Aguirre, Detre, Alsop, & D`Esposito,

C O N FL I C T O F I N T E R E S T
The authors declare that they have no conflict of interests.

1996; Byrne, Becker, & Burgess, 2007; Hartley, Maguire, Spiers,
& Burgess, 2003; Morgan, Macevoy, Aguirre, & Epstein, 2011;
Suthana, Ekstrom, Moshirvaziri, Knowlton, & Bookheimer, 2009).
Therefore, hippocampal dysfunction in patient H.W. was indicated

ORCID
Andreas Zwergal

http://orcid.org/0000-0002-3839-8398

by a nearly complete loss of his internal cognitive map for space
during the acute stage of symptoms (Hartley et al., 2003; Howard
et al., 2014). An increase in search saccades together with a pronounced deficit in the recognition and incorporation of landmarks
were associated with parahippocampal dysfunction (Aguirre et al.,

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S U P P O R T I N G I N FO R M AT I O N
Additional supporting information may be found online in the
Supporting Information section at the end of the article.

How to cite this article: Irving S, Pradhan C, Dieterich M,
Brandt T, Zwergal A, Schöberl F. Transient topographical
disorientation due to right-sided hippocampal hemorrhage.
Brain Behav. 2018;8:e01078. https://doi.org/10.1002/
brb3.1078