Seizure: European Journal of Epilepsy 86 (2021) 147–151

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Seizure: European Journal of Epilepsy

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Dr. Strangelove demystified: Disconnection of hand and language

dominance explains alien-hand syndrome after corpus callosotomy
Christoph Helmstaedter a, *, Lázló Solymosi b, Martin Kurthen c, Shahan Momjian d,
Karl Schaller d
a
Department of Epileptology, University of Bonn, Bonn, Germany
b
Department of Neuroradiology, University of Bonn, Bonn, Germany
c
Swiss Epilepsy Clinic Lengg, Zürich, Switzerland
d
Department of Neurosurgery, Geneva University Medical Center & Faculty of Medicine, Geneva, Switzerland

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Alien hand syndrome (AHS) is a disabling condition in which one hand behaves in a way that the
Callosotomy person finds "alien". This feeling of alienation is related to the occurrence of movements of the respective hand
Alien hand performed without or against conscious intention. Most information on AHS stems from single case observations
Hemisphere dominance
in patients with frontal, callosal, or parietal brain damage.
Methods: Retrospective analysis of distinctive clinical features of three out of 18 epilepsy patients who developed
AHS with antagonistic movements of the left hand after corpus callosotomy (CC) (one anterior, two complete) for
the control of epileptic seizures, particularly epileptic drop attacks (EDA).
Results: Remarkably, these three patients, two men and one woman, displayed atypical language dominance with
a bilateral, left more than right hemisphere language representation in intracarotidal amobarbital testing before
surgery. The overall additional distinctive feature of the target patients was genuine left-handedness, with
writing retrained to right-handedness in two patients. After surgery the left hands became alien. The problem
was permanent, despite strategies for compensation.
Conclusion: From this observation we suggest that under the conditions of dissociation of language and motor
dominance, loss of both intentional control of contralateral action and physiological inhibition of antagonistic
movements lead to post-callosotomy alien-hand-like motor phenomena. The dissociation pattern posing this risk
seems rare but needs to be considered when evaluating candidates for callosotomy.

1. Introduction Meanwhile different subsyndromes are subsumed under "AHS", which,

Many clinical neuroscientists are familiar with the character of Dr.
Strangelove in the iconic Stanley Kubrick movie of 1964. During his
audition in the war room of the US government Strangelove’s right arm
jumps up repeatedly for the “Hitlergruss”, while his left hand can hardly
cope to prevent these seemingly purposeful but involuntary movements.
Later, this was coined to signify the presence of an alien hand syndrome
(AHS) in Dr. Strangelove by the referring literature [1].
In a clinical context, the phenomenon of a hand (mostly the left, but
in Strangelove the right) behaving in a contextual but unintended
manner, and seemingly detached of any voluntary control was described
first by the German neurologist-psychiatrist Kurt Goldstein in the early
20th century [2]. In the early 1970ies the term AHS was introduced [3].
in what follows, will refer to as alien-hand-like motor phenomena
(AHLMP) [4–7].
Frontal, callosal, and posterior lesions are discussed as being causal
for AHS [7,8]. However, as variable as the underlying lesions are the
clinical manifestations of AHS. Risk factors for the occurrence of AHS,
and particularly AHLMP, remain unknown. There is ongoing discussion
as to whether a split brain harbors a split consciousness [9].
Here we focus on callosal AHLMP with characteristic antagonistic
behavior of the alien non-dominant hand. While AHLMP-variants have
been identified as consequences of callosotomy [4,5] patterns of hemi­
spheric specialization have not been addressed. Callosal disconnection
phenomena gained major interest in the context of Sperry’s Nobel prize
winning split-brain observations and experiments in cats, monkeys, and

* Corresponding author at: Department of Epileptology, University Hospital Bonn, Building 83, Venusberg - Campus 1, 53127 Bonn, Germany.
E-mail addresses: C.Helmstaedter@uni-bonn.de, Christoph.Helmstaedter@ukbonn.de (C. Helmstaedter).

https://doi.org/10.1016/j.seizure.2021.02.013
Received 19 January 2021; Received in revised form 10 February 2021; Accepted 11 February 2021
Available online 16 February 2021
1059-1311/© 2021 British Epilepsy Association. Published by Elsevier Ltd. This article is made available under the Elsevier license
(http://www.elsevier.com/open-access/userlicense/1.0/).
C. Helmstaedter et al. Seizure: European Journal of Epilepsy 86 (2021) 147–151

Table 1
Pre- and post-operative clinical and neuropsychological characteristics of all n = 18 patients, who underwent CC at the Epilepsy Center.
No-AHS AHS

N (%) 15 (83%) 3 (17%)

gender m/f (f%) 7/15 47% 1/3 33%
age (yrs.) 20 ± 9 30 ± 9
Education/IQ
- average 1 7% 1 33%
- borderline 2 13% 1 67%
- impaired 8 53% /
- severely impaired 4 27% /
Handedness
- right 13 86% /
- left 1 1 (writing with left)
- ambidextrous 1 /
- left retrained to right / 2 (writing with right)
age at epilepsy onset 8.6 ± 2 6.8 ± 5
Type of epilepsy/etiology:
- Lennox 5 33% 1
- cryptogenic 4 27% 1
- perinatal lesion 1
- migration disorder 1 1
- tuberous sclerosis 1
- idiopathic 1
- cryptogenic frontal 1
- post meningitis 1
Seizures:
- generalized & drop attacks 15 (100%) 3 (100%)
IAT language dominance:
- left dominant 10 (67%) (9 right-handed, one ambidextrous) /
- left > right dominant 3 (20%) (3 right-handed) 3 (100%) (3 genuine left handed)
- bilateral / /
- right dominant 2 (13%) (one right-handed, one left-handed) /
Callosotomy:
- anterior 7 47% 1 33%
- posterior 6 40% / /
- complete 2 13% 2 67%
4.1 ± 4 3.6 ± 3
Follow-Up interval (yrs.)
range: 1− 14 range: 2− 7
Postcallosotomy seizure control:
- drop attack free 7 53% 1 33%
- free of other seizures 1 7% / /
Cognitive development:
- improved 1 7% / /
- unchanged 8 53% 1 33%
- worsened 6 40% 2 67%

later in man, who contributed a lot to the understanding of the
higher-order, cognitive capacities of the non-dominant right hemisphere
and the role of the corpus callosum in interhemispheric communication
[10].
The present report is not intended to explain alien hand in general.
We aim, however, to understand AHS in terms of a functional anatom­
ical approach in a subset of patients who underwent corpus callosotomy
(CC) for otherwise intractable epilepsy (EDA). Most importantly, the
question of the determinants of AHS can be addressed more adequately
when (atypical) functional hemisphere dominance patterns are taken
into consideration.
Microsurgical anterior 2/3 callosotomy and/or complete callos­
otomy are established disconnective epilepsy surgical techniques for the
treatment of otherwise intractable epilepsies with rapid bihemispheric
seizure spread leading to epileptic drop attacks (EDA). Since discon­
nection symptoms may increase with the amount of corpus callosum
transected some surgeons recommend starting anterior, others posterior
[11,12]. Notably, disconnection at the level of the SMA may cause AHS
[13].
2. Methods and materials
The goal of the present clinical study is to identify risk factors and to
understand the mechanism of postoperative AHS observed in three pa­
tients by the re-evaluation of the presurgical process and of the surgical
procedure in our epileptic patients, who underwent callosotomy for
treatment of their epileptic seizures and EDA.
2.1. Patients
We retrospectively report a series of 18 patients in whom CC – either
anterior 2/3, or single-step complete, or two-step complete – was per­
formed (Table 1) in the years 1988–2000 at the Epilepsy Center in Bonn.
2.2. Language dominance assessment
All patients underwent intracarotidal amobarbital testing of lan­
guage dominance, the so called WADA Test, according to J. Wada who
first described this method in 1949 [14,15]. Language dominance was
assessed by consecutive anesthesia of the left and right hemisphere at
consecutive days assessing the following functions: series repetition,
comprehension of commands and questions, motor responses to com­
mands, naming, repetition, reading, spontaneous speech. Following
analyses of large series of patients who underwent WADA tests in Bonn,
Germany, a dominance index was routinely being calculated ranging
from –1 to 1, with scores -1 to -0.85 and 0.85 to 1 representing complete

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C. Helmstaedter et al.
right and left dominance, -0.5 to -0.85 and 0.5 to 0.85 representing
incomplete right or left dominance and -0.5 to 0.5 representing bilateral
language dominance. Neuropsychological examinations, as far as a
standardized assessment was possible, at that time made use of the tests
described in the respective publications. [16,17]. Handedness, which,
apart from language dominance, is important for what follows, was
categorized according the Oldfield Edinburgh inventory [18].
3. Results
Out of the eighteen patients, n = 15 did not develop AHS, and three
did. As it can be taken from the table the three patients who developed
AHS shared two distinctive features compared to those who did not. First
the three patients displayed atypical language dominance with left more
than right hemisphere language representation in intracarotidal
amobarbital testing before surgery. The overall additional distinctive
feature of the target patients, however, was genuine left-handedness,
with writing retrained to right-handedness in two patients. After sur­
gery the left hands became alien.
3.1. Male patient BS
Unremarkable birth and early childhood. Normal school and
apprenticeship as gardener. As child left-handed, however forced to learn to
use the right hand for writing and became ambidextrous. First seizure at 8
years. From age 15 until epilepsy surgery at the age of 22 years,
increasing frequency of up to daily seizures of three different types with
or without backward falls. Failed mono- and polytherapies before sur­
gery. Neuropsychology showed an average IQ (IQ ¼ 91). The WADA
test indicated bilateral language lateralization, with left predominance.
Tachistoscopy indicating left more than right hemisphere capacity for
language processing. After a first anterior 2/3 CC at age 22 in 1994 the
patient continued to have almost daily drop attacks, with no AHS noted.
Completion of the CC one year later controlled the drop attacks, but a
disconnection syndrome with AHS (left hand antagonizing and interfering
with right hand continuously) was evident. When he put on his pants he
needed to repeat this 5–15 times in order to get it up as intended with the
right hand instead of down with the left hand, thus presenting dia­
gonistic dyspraxia, however no signs of independent apraxia. Neuro­
psychologically he improved in regard to language-related functions. He
went back to work as a gardener, but some antagonisms persisted as he
described that during his work the right hand graps something to put it
at a certain place and that this is often directly reversed by the left hand.
Apart from left-right confusions (e.g. turning left versus right when
walking), the patient had general difficulties in decision-making. He,
different from the other two cases, called his left hand the evil hand and
he argued loudly with the hand to stop its interference. Follow-up
consultations revealed persistent control of drop attacks. AHS per­
sisted, but over time he developed defensive strategies to avoid AHS
being too incapacitating in daily life, i.e. putting the left hand in the
pocket when standing, or sitting on the hand.
In this regard we made the observation that all three patients were
sitting on their left hand in order to prevent interference while being
neuropsychologically evaluated.
3.2. Female patient MH
Unremarkable birth and early childhood. Left-handed, not retrained to
write with the right hand. Head injury at 5 years. As of 7th year devel­
opment of pyknoleptic absences and drop attacks (50–100/d), which
improved under AED. Between 20–40 years of age she experienced an
increasing frequence of psychomotor seizures and Grand Mal seizures.
At the time of extensive evaluation, three different types of seizures were
recorded: psychomotor seizures (2–4/d), drop attacks (3–4/week),
secondary generalized seizures (4/week). Neuropsychology showed a
mild mental retardation despite an IQ within the norm (IQ ¼ 90). The
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Seizure: European Journal of Epilepsy 86 (2021) 147–151
WADA test indicated bilateral language organization with left hemi­
sphere predominance. In the left WADA expressive and receptive lan­
guage functions were partly possible. In the right WADA she was
dysarthric, paraphasic and with impaired spontaneous speech and
repetition performance. She underwent anterior 2/3 CC at age 40. After
surgery she experienced reversible lack of initiation, sensory aphasia,
left-sided ataxia, and became right-handed since that time. Postoperative
neuropsychology indicated lasting impairments in attention and exec­
utive functions, verbal memory, and verbal comprehension. Over
twenty-year follow-up: No more drop attacks and completely seizure-
free under Lamotrigine, Valproate and Topiramate. After surgery she
couldn’t write any longer with her left hand and had to relearn writing
right-handed. Drawing and painting were continued to be performed
with the left hand. Starting after surgery and continuing ever since, she
experienced involuntary movements in actions which were intended
with the right hand and were executed with the left hand. In part the left
hand performed antagonistic actions, i.e. if she wants to take the light
sweater from the wardrobe with her right hand, the left takes the woolen
pullover instead. Hence, she presented with agonistic dyspraxia and
intermanual conflict. No signs of independent apraxia.
3.3. Male patient FB
Unremarkable early childhood. As child left-handed. Was then forced
to learn to use right hand. Normal performance at primary and then basic
high school. First tonic-clonic seizure at 11 years. Became seizure free
with AED until age 15, when he had his first drop attack. Drop attacks
increased in frequency, and apprenticeship as office assistant was
stopped. No complete seizure control with double and triple AED
medication. Neuropsychology showed IQ at lower limit of the norm (IQ
¼ 85). The WADA test indicated bilateral language lateralization, with
left sided predominance. Expressive language was mostly left repre­
sented, i.e. not possible in the left but right WADA, receptive language
functions were bilaterally, i.e. present during the left and right WADA.
Complete CC was performed at age 27. Postoperatively, this patient had
serious problems with writing and drawing with the right hand.
Throughout the ensuing seven years the patient suffered from a discon­
nection syndrome with AHLMP: after surgery the non-dominant left hand
increasingly started to antagonize the dominant right hand. He dis­
played intermanual conflict or diagonistic dypsraxia, respectively. As for
the seizure situation he experienced repeated EDA.
4. Discussion
The present study reveals common and specific features associated
with AHS in terms of anatagonistic actions in three out of 18 patients,
who underwent callosotomy for the control of their drop attacks. The
principal rationale of CC is to prevent rapid interhemispheric spread of
seizure activity leading to tonic or atonic falls – taking into account that
disconnecting the two hemispheres may have disabling complications
which however are outweighted by the control of the drop attacks.
Split-brain phenomena after callosotomy were detected and
described early, leading to fascinating knowledge about the human
brain’s hemispheric functional organization and the decisive role of the
Corpus callosum’s involvement in interhemispheric communication and
inhibition. AHS after callosotomy is a serious complication, which ren­
ders identification of risk factors is highly desirable.
We identified specific hemispheric dominance patterns as risk factors
for AHS after callosal lesions. The Wada test assesses the functioning
versus inactivation of one hemisphere by consecutive separate anaes­
thetization of the left and right hemispheres [14]. The procedure sim­
ulates unilateral surgical adamage and reveals contralateral
reserve-capacities for compensation and recovery [19]. In our patients
the test was performed to prevent disconnection of language systems,
such as in crossed language dominance [20], and to prevent the
disconnection of language and hand-dominance resulting for example in
C. Helmstaedter et al.
agraphia [21].
Unknown at that time was the outcome of callosotomy in a
dominance-pattern with bilateral language-dominance with a predom­
inance in the left hemisphere and a right-hemispherical dominance for
handedness, i.e. genuine left-handedness, retrained to right-handedness
in two of the three patients. Screening the clinical and surgical features
of our patient series, the disconnection of two hemispheres, which were
differentially dominant for language and motor functions appears the
plausible and distinctive feature that differentiates patients who devel­
oped AHS from those who did not. In our three AHS patients, the left
hemisphere was dominant, but not exclusively for language functions,
while the right hemisphere had some capacities for language and was
dominant for motor functions. It is likely that under this condition the
right hemisphere has enough capabilities for own actions in intentional
activities, which due to callosal disconnection cannot be inhibited by the
left hemisphere, which intends to initiate and lead the individual’s ac­
tions. Normally, the language-dominant (mostly left) hemisphere, due to
its digital and sequential information processing mode, is the one which
organizes skillful action. Apraxia is a common problem, apart from
aphasia, in left-hemispherically damaged patients. After callosotomy,
the leading left hemisphere in the three AHS-patients was left over with
an inferior action control for the right hand. The two patients, who had
been retrained to write with their right hand could continue to use their
right hand for writing, one more successful than the other. The female
patient, however, who was not trained to write with the right hand
became agraphic for the left hand and had to learn writing with the
right. She continued drawing and painting with her left hand, in line
with the right hemisphere’s visual spatial processing capabilities. In all
three patients the right hemisphere, controlling the genuine dominant
left hand became capable to act on its own, presumably because of
additional inferior left-hemispherical practical capacities with access to
the motor system. Before callosotomy such independent actions were
most likely suppressed and inhibited via callosal communication and
inhibition of action control and motor execution (see schematic figure).
It seems as though a complete dissociation results in a clean "division of
labor" between the hemispheres, while partial dissociation tends to
bring about conflicting processing efforts.
Why callosal disconnection results in antagonistic and not just some
otherwise dissociated motor action requires additional explanations.
The right hemisphere in AHS appears to have no independent intention
or scheme for action and follows the action design chosen by the
language-dominant left hemisphere to account for the respective situa­
tional affordance. However, the alien hand actions are antagonistic
rather than simply a copy of the intended action program or supportive
in some way.
Precise motor planning requires bilateral hemispherical activiation,
and it includes the inhibition of antagonistic movements [7]. Activities
are represented in mental mirror images as indicated for example by the
phenomenon of mirror writing. Mirror movements are ‘involuntary
movements of one body part that mirror the voluntary movement of the
contralateral homologous body part’ [22]. Alteration of transcallosal
projections inhibiting controlaterally generated ipsilateral movements is
discussed as one explanation for mirror movements [23]. Detachment of
the dominant hand from proper motor planning with subsequent lack of
suppression of contralateral mirror and antagonistic movements,
through CC or other damage of the corpus callosum, may explain the
clinical manifestation of antagonistic AHS of the left side [24,25].
One of the male patients, who was retrained to right-handedness,
developed AHS only after completion of the callosotomy. Following
what has been described as the anterior motor form of AHS, or the pure
callosal form, the disconnection of the motor system including premotor
areas and SMA, which are involved in motor programming, execution
and feedback-guided adjustment, would suffice to explain AHS [7,26].
The relevant mechanism may be a dissociation of language and motor
dominance and a loss of both intentional control of contralateral action
and physiological inhibition of antagonistic movements (see Fig. 1).
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Seizure: European Journal of Epilepsy 86 (2021) 147–151
Fig. 1. Distribution and functional connections (+) and inhibitions (-) of left >
right hemisphere language dominance and right hemisphere motor dominance
(MH), handedness having been retrained in patients BS and FB. The post-
callosotomy (CC) patterns indicate the disconnection of interhemispheric
communication and inhibition, leaving the two hemispheres with opposite
within hemisphere distributions of language and motor control.
The scheme also explains why patient MH, who had not been forced to write
right-handed had to learn writing with the right hand after callosotomy.
As for Dr. Strangelove, it seems reasonable that as an act of artistic
freedom the spectacular split-brain research of that era was associated
with the prototypical involuntary right arm “Sieg Heil” Hitlergruß in the
movie. Scientifically, Dr. Strangelove’s right hand AHS might be clas­
sified as one of rare cases of right alien hands [27], which are not
behaving antagonistic, and which would fit to Feinbergs frontal right
(dominant) hand AHS [26]. Another interpretation, which was probably
not indended but which would fit better to non-dominant AHS could be
an explanation according to which the right hand’s action was intended
and the left alien hand tried to revert this action.
Finally, for clinical practice, a dissociated hemispehere dominance
pattern of bilateral language and genuine left handedness (right hemi­
sphere motor dominance) should raise a red flag in candidates for cal­
losotomy. We, on the basic of our finding, would not recommend
callosotomy in such cases but since we didn’t find comparable cases
reported in the literature knowledge of any callosotomy patients with
the same dominance pattern not resulting in AHS would surely be of
major interest.
Declaration of authorship
C. Helmstaedter: data collection from patient files, writing, inter­
pretation, figure.
K. Schaller: data collection from patient files, writing, interpretation,
figure.
M. Kurthen: writing, interpretation.
S. Momjian: literature search, interpretation.
L. Solymosi: literature search, collection of MR reports and surgical
reports.
Declaration of Competing Interest
Dr. Helmstaedter reports grants from ERN EpiCare, personal fees
from Eisai, personal fees from UCB, personal fees from GW, other from
Seizure Elsevier, personal fees from Precisis, outside the submitted
work; In addition, Dr. Helmstaedter has a patent EpiTrack licensed to
UCB, a patent EpiTrack licensed to Eisai, a patent NeuroCogFX licensed
to Eisai, and a patent EpiTrack licensed to Precisis.
The authors report no declarations of interest.
C. Helmstaedter et al. Seizure: European Journal of Epilepsy 86 (2021) 147–151

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