Epilepsia, 51(10):2131–2139, 2010

doi: 10.1111/j.1528-1167.2010.02723.x

FULL-LENGTH ORIGINAL RESEARCH

Brain activation patterns of versive, hypermotor, and bilateral

asymmetric tonic seizures
*yChong H. Wong, *zArmin Mohamed, *xGeorge Larcos, {Rochelle McCredie,
y**Ernest Somerville, and *yAndrew Bleasel

*Faculty of Medicine, University of Sydney, NSW, Australia; yDepartment of Neurology, Westmead Hospital, Westmead, NSW,
Australia; zDepartment of PET and Nuclear Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; xCentre for
Biomedical Imaging, Research & Development and Department of Nuclear Medicine & Ultrasound, Westmead Hospital, Westmead,
NSW, Australia; {Department of Medical Physics, Westmead Hospital, Westmead, NSW, Australia; and **Department of
Neurology, Prince of Wales Hospital, Randwick, NSW, Australia

cluster-level significance p < 0.05 were considered signif-

SUMMARY
Purpose: Patients who have seizure onset from different
brain regions can produce seizures that appear clinically
indistinguishable from one another. These clinically
stereotypic manifestations reflect epileptic activation of
specific networks. Several studies have shown that ictal
perfusion single photon emission computed tomography
(SPECT) can reveal propagated ictal activity. We hypoth-
esize that the pattern of hyperperfusion may reflect
neuronal networks that generated specific ictal symptom-
atology.
Methods: All patients were identified who were
injected with 99mTc-hexamethyl-propylene-amine-oxime
(HMPAO) during versive seizures (n = 5), bilateral
asymmetric tonic seizures (BATS; n = 5), and hypermo-
tor seizures (n = 7) in the presurgical epilepsy evaluation
between 2001 and 2005. The SPECT ictal–interictal dif-
ference image pairs of each subgroup were compared
with image pairs of 14 controls using statistical para-
metric mapping (SPM 2) to identify regions of significant
hyperperfusion. Hyperperfused regions with corrected
icant.
Results: We have identified a distinct ictal perfusion
pattern in each subgroup. In versive seizure subgroup,
prominent hyperperfusion was present in the frontal eye
field opposite to the direction of head version. In addition,
there was associated caudate and crossed cerebellar
hyperperfusion. The BATS subgroup showed pronounced
hyperperfusion supplementary sensorimotor area ipsilat-
eral to the epileptogenic region, bilateral basal ganglia,
and contralateral cerebellar hemisphere. The hypermo-
tor seizure subgroup demonstrated two clusters of signifi-
cant hyperperfusion: one involving bilateral frontomesial
regions, cingulate gyri, and caudate nuclei, and another
involving ipsilateral anteromesial temporal structures,
frontoorbital region, insula, and basal ganglia.
Discussion: We have identified distinct hyperperfusion
patterns for specific ictal symptomatology. Our findings
provide further insight into understanding the anatomic
basis of seizure semiology.
KEY WORDS: Partial seizures, SPECT in epilepsy, Epi-
lepsy semiology.

Epileptic seizures are often characterized based on care-
ful analysis of the semiologic features during seizures
(Luders et al., 1998; So, 2006; Noachtar & Peters, 2009).
However, the anatomic basis underlying several clinical
signs occurring during partial seizures remains unclear.
Direct cortical electrical stimulation or electrocorticograph-
ic recording has been attempted previously to unravel the
mechanisms of ictal symptomatology, but these methods
Accepted July 19, 2010; Early View publication September 22, 2010.
Address correspondence to Dr Andrew Bleasel, Department of
Neurology, Westmead Hospital, Darcy Road, Westmead, NSW 2145,
Australia. E-mail: ableasel@usyd.edu.au
Wiley Periodicals, Inc.
ª 2010 International League Against Epilepsy
are constrained by limited spatial sampling and current
spread (Luders et al., 1987; Lim et al., 1994). Ictal radionu-
clide brain perfusion single photon emission computed
tomography (SPECT) can provide a global appraisal of
brain activity at one phase in the seizure. Although it is used
primarily in the presurgical evaluation of refractory epilepsy
to localize the ictal onset zone, ictal SPECT also shows
hyperemic regions representing propagated ictal activity to
the symptomatogenic zone because radiopharmaceutical is
injected after noting seizure onset (Van Paesschen et al.,
2007). Therefore, the topography of ictal hyperperfusion
should reflect activated structures responsible for the evolu-
tion of symptomatology in the course of the seizure. In this
study, we have examined ictal SPECT scans of patients with

2131
2132
C. H. Wong et al.
same seizure semiology to identify the neuronal networks
generating specific ictal symptomatology.
Patients and Methods
Patient selection
The study was approved by the ethics committee in
Western Sydney Area Health Services. Between 2001 and
2005, 229 scalp video–electroencephalography (EEG) mon-
itoring sessions were performed in 213 patients for presurgi-
cal evaluation of medically intractable partial epilepsy at
Westmead Hospital. During video-EEG monitoring, 147
patients were injected with 99mTc-hexamethyl-propylene-
amine-oxime (99mTc-HMPAO) during a seizure. For this
study, we identified all patients who were injected with
99m
Tc-HMPAO immediately prior (<10 s) or during versive
seizures (n = 7), bilateral asymmetric tonic seizures
(BATS; n = 8), and hypermotor seizures (n = 7). From
these groups, patients who developed secondarily general-
ized tonic–clonic seizures (n = 2) and patients with previ-
ous brain surgery were excluded (n = 3).
Seizure semiology and determination of
99m
Tc-HMPAO-SPECT injection timing
Seizures were defined according to the semiologic sei-
zure classification (Luders et al., 1998). Versive seizures
are seizures with sustained and extreme degree of head and
eye deviation to one side (Wyllie et al., 1986). The versive
movements are often accompanied by small clonic lateral
movements of the head, and the chin moves not only later-
ally but also upwards (Luders et al., 1998). BATS are sei-
zures characterized by tonic posturing involving the trunk
and limbs that is bilateral but asymmetric (Bleasel &
Luders, 2000). Hypermotor seizures consist of complex,
organized movements affecting predominantly the proximal
segments of the limbs and trunk, resulting in large move-
ments that may appear ‘‘violent’’ when they occur at high
speeds (Luders et al., 1998).
The timing of the 99mTc-HMPAO injection was deter-
mined on retrospective video and EEG review. Seizure
onset was defined as the earliest EEG or clinical evidence of
seizure activity (McNally et al., 2005) and seizure cessation
when no EEG evidence of seizure activity was present.
99m
Tc-HMPAO-SPECT acquisition, image processing,
and SPM analysis
Approximately 800 MBq of 99mTc-HMPAO was injected
as a bolus into either a cephalic or an antecubital vein of the
forearm after noting seizure onset. 99mTc-HMPAO–SPECT
images were acquired within 4 h of injection. Patients with
a seizure duration lasting <30 s were allocated a trained
nurse to sit by the bedside for radiopharmaceutical injection,
whereas those with a seizure of greater duration relied on a
trained nurse responding to a seizure alarm for radiopharma-
ceutical injection. Interictal 99mTc-HMPAO–SPECT in the
Epilepsia, 51(10):2131–2139, 2010
doi: 10.1111/j.1528-1167.2010.02723.x
same patients was obtained after >24 h of no seizure activ-
ity. 99mTc-HMPAO–SPECT images of the brain were
acquired using Siemens Orbiter (Siemens Healthcare, Hoff-
man Estates, IL, U.S.A.) single head gamma camera with
neurofocal collimator and ADAC (Milpitas, CA, U.S.A.)
Vertex and ADAC Forte dual head cameras with fanbeam
collimators. Sixty-four projections were collected on a
128 · 128 matrix. The projection images were recon-
structed with filtered back projection (Butterworth filter,
0.2–0.4 Nyquist cutoff frequency, 10th order) and corrected
for attenuation using the Chang analytic method.
In the versive seizure subgroup, the direction of head
turning can be defined clearly. We transposed horizontally
the SPECT images of patients with right head deviation and
combined them with the patients with left head deviation
using IMAGEJ (Rasband, 1997–2009). Therefore, the direc-
tion of head turn was uniform assuming the homologous
symptomatogenic network was represented on the contralat-
eral side to the head deviation. In hypermotor seizures and
BATS, it was not possible to normalize to a lateralized
motor feature because motor manifestations were complex
or consisted of bilateral tonic posturing. As such, we flipped
the SPECT images so that all the ictal onsets were lateral-
ized to the left, assuming seizures will propagate to involve
a consistent network responsible for the semiology.
99m
Tc-HMPAO–SPECT was pre-processed as described
by McNally et al. (2005) using Statistical Parametric Map-
ping (SPM 2, Wellcome Department of Cognitive Neurol-
ogy, London, United Kingdom). Details of pre-processing,
including downloads of 14 healthy normal SPECT image
pairs from normal subjects, are available at http://spect.
yale.edu/. In brief, SPECT images were realigned, spatially
normalized, and smoothed by convolution with 16-mm
Full-Width Half-Maximum (FWHM) Gaussian kernel.
Global intensity normalization using proportional scaling
with an analysis threshold of 0.8 was applied. For statistical
analysis, SPECT ictal–interictal difference image pairs of
each subgroup were compared voxel-by-voxel with image
pairs of 14 healthy normal controls using multigroup condi-
tion and covariates model (McNally et al., 2005) to identify
all clusters of voxels with significant hyperperfusion.
Significant hyperperfusion was defined as clusters with cor-
rected cluster-level significance p < 0.05 (voxel threshold
p = 0.01, extent threshold ‡ 125).
Results
The results of patient demographics are summarized in
Table 1. Five patients with versive seizure, five with BATS,
and seven with hypermotor seizure were studied. The med-
ian age was 24 years [interquartile range (IQR) 25–75%:
21–34; range 11–43]. Fifteen patients underwent resective
surgery. In the nine surgical patients with normal magnetic
resonance imaging (MRI), invasive subdural electrode eval-
uation and electrocorticography were carried out to

Table 1. Patient demographics
Gender (female/male)
Age (years, median; range)
Age of onset (years, median; range)
MRI visible lesion
Surgical outcome [Engel class 1 (total patient operated)]
Seizure duration (seconds, median; range)
Radiopharmaceutical injection in relation to seizure onset (seconds, median; range)
F, frontal lobe; T, temporal lobe; O, occipital lobe.
determine the region of ictal onset, the areas involved in
early propagation, and the proximity to eloquent cortex
prior to resection. Postoperatively, 12 patients achieved
Engel class I seizure freedom (Table 2).
SPM analysis revealed a distinctive pattern of significant
ictal hyperperfusion in each subgroup (Fig. 1 and Supple-
mental Fig. S1–3) as follows:
1. Versive seizure subgroup showed a prominent hyperper-
fusion anterior to the precentral sulcus in the frontal eye
field opposite to the direction of the head turn. In addi-
tion, there was associated ipsilateral caudate and crossed
cerebellar hyperperfusion.
2. BATS subgroup showed pronounced hyperperfusion in
the supplementary sensorimotor area (SSMA) ipsilateral
to the hemisphere of ictal onset and bilateral basal gan-
glia. Crossed cerebellar hyperperfusion was also present.
3. Hypermotor seizure subgroup demonstrated two clus-
ters of significant hyperperfusion: one involving both
frontomesial regions, cingulate gyri, and caudate nuclei,
and another involving ipsilateral temporal pole, mesial
temporal structures, frontoorbital region, insula, and
basal ganglia.
Discussion
The major finding of our work is that specific perfusion
patterns are associated with different ictal semiology. Our
study was based on the concept that the same ictal symptom-
atology resulted from activation of the same cortical
network (Spencer, 2002), and by analyzing groups of
patients injected in the same ictal semiology we hypo-
thesized the brain regions most consistently involved
could be identified by quantitative voxel-based analysis on
99m
Tc-HMPAO–SPECT.
Despite the varied location of seizure onset and histopa-
thology, similar semiologic features during seizures can
exist. This observation had been reported previously by
several investigators (Wyllie et al., 1986; Bleasel et al.,
1997; So, 2006). The network structures within the brain are
connected functionally and structurally. It is not surprising
that seizures arising from different sites can propagate in a
2133
SPECT Patterns and Seizure Semiology
Versive Bilateral asymmetric Hypermotor
seizure tonic seizure seizure
2:3 3:2 3:4
23; 11–27 30; 18–42 24; 16–43
7; 4–11 10; 8–17 13; 2–21
F = 1, T = 2, O = 2 0 T=1
5 (5) 3 (4) 4 (6)
115; 27–323 34; 11–64 47; 9–157
88; 7–113 7; 3–37 14; 5–54
variably extensive way to involve the same neural network
(Spencer, 2002).
In our cohort of versive seizures, forced and sustained
head and eye version was associated with pronounced hyp-
erperfusion in the contralateral frontal eye field. In addition,
there was associated contralateral with caudate and ipsilat-
eral cerebellar hyperperfusion. In another SPECT study,
head turning was also noted to be associated with increases
in cortical blood flow on the hemisphere opposite to the
direction of version (Newton et al., 1992). Wyllie et al.
(1986) found versive head and eye movements reliably
lateralizing the seizure onset to the contralateral hemi-
sphere. These versive movements can be elicited by direct
electrical stimulation of frontal eye field in the posterior part
of the middle frontal gyrus and the immediate adjacent part
of the superior frontal gyrus (Foerster, 1931; Godoy et al.,
1990; Blanke et al., 2000).
The basal ganglia is a complex structure implicated in a
variety of regulatory controls of movement and posture.
Hyperperfusion of this structure is often associated with
dystonic posturing of limbs during seizures. However, none
of our patients in the versive seizure subgroup had ictal dys-
tonia. Several investigators have shown that the frontal eye
field sends large direct projections to the caudate nucleus
(Leichnetz & Gonzalo-Ruiz, 1996; Cui et al., 2003). We
suggest that the caudate is part of the neuronal circuitry acti-
vated in a versive seizure.
Crossed cerebellar hyperperfusion is frequently observed
in focal seizures (Bohnen et al., 1998). This phenomenon,
like that of crossed cerebellar diaschisis (Baron et al., 1981;
Won et al., 1996), reflects perfusion alterations of structures
functionally connected through the corticopontocerebellar
pathway during seizures. The frontal lobes have extensive
efferent projections to the contralateral cerebellar hemi-
sphere (Brodal, 1972). Our finding of crossed cerebellar
hyperperfusion accords with this neuronal connection.
Several investigators recognized that electrical stimula-
tion of the SSMA could elicit sustained tonic truncal and
bilateral asymmetric limb posturing (Penfield & Welch,
1951; Woolsey et al., 1952). This characteristic posture is
also accepted by The International League Against
Epilepsia, 51(10):2131–2139, 2010
doi: 10.1111/j.1528-1167.2010.02723.x
 2134

Table 2. Summary of clinical features, investigation results, and surgical outcome

Seizure duration; Seizure outcome
Patient, (age/gender), Completion of injection to completion of Lobe of (follow-up
age onset, MRI Semiology the onset of semiology injection (s) ictal onseta Type of surgery duration)/pathology
V1. (20 years/F), onset: Visual aura (visual disturbances, 6 s prior to onset of eye 323; 113 Rt OL Rt inferior mesial Engel class 1 (8 years)
C. H. Wong et al.

7 years flashing lights) version occipital corticectomy Non–balloon cell

MRI: Rt inferior-mesial fi Versive seizure cortical dysplasia

Epilepsia, 51(10):2131–2139, 2010

occipital lobe lesion (Forced sustained eye and head
version to the left)

doi: 10.1111/j.1528-1167.2010.02723.x
fi Dialeptic seizure
(Behavioral pause, stare, not
responding to questions,
occasional subtle lip movements)
V2. (24 years/M), onset: Visual aura (strain behind both 1 s prior to onset of eye 27; 7 Rt OL Rt inferior mesial Engel class 1 (3 years)
8 years eyes, flashing lights) version occipital corticectomy Microdysgenesis
MRI: Rt inferior-mesial fi Versive seizure
occipital lobe lesion (Forced sustained eye and head
version to the left)
V3. (11 years/F), onset: Aura (lightheadedness, vagueness) 7 s prior to onset of eye 141; 88 Rt TL Rt lateral temporal Engel class 1 (8 years)
4 years fi Versive seizure version corticectomy Dysembryoplastic
MRI: Rt lateral temporal (Forced sustained eye and head neuroepithelial tumor
lesion version to the left)
V4. (27 years/M), onset: Aura (rising epigastric feeling) 13 s after onset of eye 115, 110 Rt FL Rt frontal pole Engel class 1 (8 years)
11 years fi Versive seizure version corticectomy Balloon cell cortical
MRI: Rt frontopolar lesion (Forced sustained eye and head dysplasia
version to the left)
V5. (23 years/M), onset: Aura (fearful feeling, epigastric 8 s after onset of eye 60, 45 Lt TL Lt temporal lobectomy Engel class 1 (4 years)
6 years discomfort) version Hippocampal sclerosis
MRI: Lt hippocampal fi Automotor seizure
sclerosis (Lip smacking, chewing, rubbing
hands on legs, looks around)
fi Versive seizure
(Forced sustained eye and head
version to the right)
S1. (30 years/F), onset: Bilateral asymmetric tonic seizure 7 s after onset of bilateral 30; 7 Lt FL Lt mesial frontal Engel class 1 (7 years)
8 years asymmetric tonic seizure corticectomy Non-balloon cell cortical
MRI: normal dysplasia
S2. (32 years/F); onset: Bilateral asymmetric tonic seizure 37 s after onset of bilateral 43; 37 Lt FL Not operated
17 years asymmetric tonic seizure
MRI: normal
S3. (18 years/F), onset: Bilateral asymmetric tonic seizure 28 s after onset of bilateral 64; 28 Rt FL Rt mesial frontal Engel class 1 (8 years)
10 years asymmetric tonic seizure corticectomy Neuronal heterotopia
MRI: normal
Continued
 Table 2. Continued
Seizure duration; Seizure outcome
Patient, (age/gender), Completion of injection to completion of Lobe of (follow-up
age onset, MRI Semiology the onset of semiology injection (s) ictal onseta Type of surgery duration)/pathology
S4. (23 years/M), onset: Aura (unusual feeling in left leg) 1 s prior to onset of bilateral 11; 3 Rt FL Rt mesial Engel class 1 (2 years)
14 years fi Bilateral asymmetric tonic asymmetric tonic seizure frontoparietal Balloon cell cortical
MRI: normal seizure corticectomy dysplasia
S5. (42 years/M); onset: Bilateral asymmetric tonic seizure 4 s after onset of bilateral 34; 4 Rt FL Rt mesial frontal Engel class II (6 years)
10 years asymmetric tonic seizure corticectomy Non–balloon cell
MRI: normal cortical dysplasia
H1. (36 years/F), onset: Aura (sounds become distant; sense 3 s after onset of hypermotor 97; 19 Rt TL Rt temporal Engel class 1 (3 years)
13 years of impending doom) seizure lobectomy Hippocampal sclerosis
MRI: Rt hippocampal fi Hypermotor seizure:
sclerosis (Covers face with left hand; turning
vigorously in bed; whimpering vocalization)
H2. (16 years/M), onset: Aura (fearful feeling) 6 s after onset of hypermotor 26; 10 Rt FL Rt frontomesial Engel class 1 (3 years)
13 years fi Hypermotor seizure: seizure corticectomy Neuronal heterotopia
MRI: normal (Looks around in a restless manner;
rocking of body back and forth;
shuffling from side to side; sniff heavily;
fumbling with clothing)
H3. (43 years/M), onset: Aura (fearful feeling) At onset of hypermotor seizure 39; 14 Rt TL Rt temporal Engel class 1 (5 years)
21 years fi Hypermotor seizure: lobectomy Neuronal heterotopia
MRI: normal (Looks around in a restless manner;
rocking of body back and forth; shuffling
from side to side; chews, lip smacking;
fumbling with clothing).
H4. (24 years/F), onset: Aura (feels hot in the head and going to 43 s after onset of hypermotor 65; 54 Rt FL or TL Not operated
16 years blackout) seizure
MRI: normal fi Hypermotor seizure:
(Rocking of body back and forth with facial
grimacing; grabbing pillows; turning
vigorously in bed; whimpering vocalization)
H5. (23 years/F), onset: No Aura 41 s after onset of hypermotor 157; 41 Lt FL Lt dorsolateral frontal Engel class 1 (4 years)
2 years fi Hypermotor seizure: seizure corticectomy Neuronal heterotopia
MRI: normal (Moving both arms in a restless manner;
rocking of body back and forth; shuffling
from side to side; whimpering vocalization)
H6. (22 years/M), onset: Aura (feels dizzy or a sense of leg weakness) 10 s after onset of hypermotor 47; 13 Lt FL Lt frontomesial Engel class III (6 years)
11 years fi Hypermotor seizure: seizure corticectomy Neuronal heterotopia
MRI: normal (Rocking of body back and forth; shuffling
from side to side; scissoring of legs; jumping
in and out of bed; frenetic and large amplitude
peddling movements of lower limbs;
writhing trunk)
Continued
SPECT Patterns and Seizure Semiology

doi: 10.1111/j.1528-1167.2010.02723.x
Epilepsia, 51(10):2131–2139, 2010
2135
2136
C. H. Wong et al.

Epilepsy (ILAE) to be one of the distinctive ictal semiolo-

Engel class II (5 years)

duration)/pathology
gies characteristic of SSMA seizures (Commission, 1989).
Seizure outcome

Microdysgenesis
The mechanism underlying bilateral motor activities is
(follow-up debated. Chauvel et al. (1992) found epileptic discharge
spread from ipsilateral SSMA into the contralateral SSMA

Lobe of ictal onset was determined based on clinical history, scalp, and intracranial video-EEG monitoring, MRI, fluorodeoxyglucose (FDG) –PET, HMPAO–SPECT, and neuropsychological studies.
during BATS and postulated that this was the mechanism of
bilateral motor manifestations. However, it is also known
that unilateral SSMA damage can produce bilateral motor
Lt fronto-orbital
Type of surgery

impairment (Laplane et al., 1977; Zentner et al., 1996).

corticectomy

Our SPM analysis suggested that ictal activation confined

to one SSMA produces BATS. In our BATS subgroup, the
subcortical activation pattern involved bilaterally basal gan-
glia and contralateral cerebellum. This subcortical pattern is
consistent with known projections from SSMA to bilateral
ictal onseta

basal ganglia and contralateral cerebellum (Wiesendanger,

Lobe of

1986). Laich et al. (1997) examined SSMA propagation

Lt FL

pathways using ictal SPECT and found similar subcortical

hyperperfusion pattern involving bilateral basal ganglia and
Seizure duration;

contralateral cerebellum. However, only two of their six

completion of

patients with bilateral asymmetric tonic posturing had ipsi-

injection (s)

lateral SSMA hyperperfusion, whereas the rest showed

bilateral but asymmetric frontomesial hyperperfusion with
9; 5

predominance ipsilateral to the ictal onset. It is possible that

the stringent criteria of our SPM analysis did not show bilat-
Table 2. Continued

eral SSMA hyperperfusion because involvement of contra-

2 s after onset of hypermotor
Completion of injection to

lateral SSMA is not sufficiently consistent to produce a

the onset of semiology

sufficiently large perfusion increase in the group analysis.

Further investigation will be needed to determine the
mechanism, but in any case, not all patients with bilateral
asymmetric tonic posturing had bilateral frontomesial
seizure

hyperperfusion.
In patients with hypermotor seizure, two clusters of sig-
M, male; F, female; Rt, right; Lt, left; FL, frontal lobe; TL, temporal lobe; OL, occipital lobe.

nificant hyperperfusion were present. One cluster involved

bilateral frontomesial regions, cingulate gyrus, and caudate,
(Screams; complex arm movements; legs kicking

and the other involving ipsilateral temporal pole, mesial

shuffling from side to side, turning vigorously
Aura (feels his face is being pulled forward)

temporal structures, frontoorbital region, insula, and basal

violently; rocking of body back and forth;

ganglia. The precise symptomatogenic zone for hypermotor

seizures remains largely unknown, although there is increas-
ing evidence that it involves the orbitofrontal cortex and
anterior cingulate cortex (Schlaug et al., 1997; Rheims
fi Hypermotor seizure:

et al., 2008). Rheims et al. (2008) reported the hypermotor

in bed; back arching)

seizures consisting mainly of body rocking, limb hyperki-

netic movements, and facial expression of fear showed
stereoelectroencephalography (SEEG) ictal changes cen-
Semiology

tered mainly on the ventromesial frontal cortex, whereas

hypermotor seizures consisting of truncal movements or
rotation with frequent tonic/dystonic posturing showed
changes localized within the mesial premotor cortex and
H7. (37 years /M), onset:

dorsal anterior cingulate. These reported electrical changes

Patient, (age/gender),

overlap with our regions of hyperperfusion. However, this

study had technical limitations of SEEG spatial sampling
age onset, MRI

and did not include all patients with hypermotor seizure.

MRI: normal
12 years

Nobili et al. (2004) recently reported three patients with

hypermotor seizures, symptomatic of temporobasal cortical
a

dysplasia, where SEEG showed temporal lobe ictal onset. In

Epilepsia, 51(10):2131–2139, 2010
doi: 10.1111/j.1528-1167.2010.02723.x
 2137
SPECT Patterns and Seizure Semiology

Figure 1.
In versive seizure subgroup (top),
significant hyperperfusion was
identified in the middle frontal gyrus
and the adjacent cortex opposite to
the direction of the head turn.
Ipsilateral caudate and contralateral
cerebellum significant hyperperfu-
sion was also present. In the bilat-
eral asymmetric tonic seizure
subgroup (middle), significantly
hyperperfusion involved primarily
the supplementary sensorimotor
area ipsilateral to the hemisphere of
ictal onset, bilateral basal ganglia,
and contralateral cerebellum. In the
hypermotor seizure subgroup
(bottom), two clusters of significant
hyperperfusion were found: One
involved bilateral frontomesial
cortex and cingulate gyrus, and the
other involved the temporal lobe,
frontoorbital cortex, insula, and
basal ganglia ipsilateral to the
hemisphere of ictal onset.
Epilepsia ILAE

the study, they found that hypermotor manifestations
appeared only when the ictal discharge in the temporal lobe
involved extratemporal structures such as the cingulate and
frontal regions. The orbitofrontal cortex and anterior cingu-
late cortex are reciprocally connected and they are linked
extensively to the mesial frontal regions, amygdala, hippo-
campus, temporal pole, insula, and basal ganglia (Salloway
et al., 2001). Our data support the hypothesis that the entire
circuitry participates in the expression of hypermotor
seizure.
Shin et al. (2002) examined the ictal SPECT in patients
with seizures of mesial temporal lobe origin and showed
that ictal hyperperfusion patterns were related to the semio-
logic progression of seizures. In our study, group analysis
was performed to eliminate interindividual perfusion
variability and identify consistent hyperperfusion pattern.
However, SPECT injection was performed without depth
electrode or subdural grid electroencephalographic record-
ing, and several of our patients were injected during the
expression of the specified semiology. Taking into account

Epilepsia, 51(10):2131–2139, 2010

doi: 10.1111/j.1528-1167.2010.02723.x
2138
C. H. Wong et al.
a 30 s transit time for 99mTc-HMPAO injection to reach
the brain and that brain uptake reaches maximum within
1 min after injection (Andersen, 1989; Pastor et al., 2008),
it is, therefore, possible that some of the perfusion changes
may be postictal. Future study of patients with same semi-
ology injected 30 s prior to manifestation of the semiologic
features with seizure lasting a minute or more will be
needed to confirm our findings. Another potential limita-
tion of our study is our small sample size. Different SPECT
gamma cameras used during the study duration can add
also heterogeneity to 99mTc-HMPAO–SPECT data. To
address this issue, we used a large Gaussian kernel filter to
smooth images before beginning the statistical analysis.
SPECT has been used to study dystonic limb posturing
during seizures and associated this ictal sign with contralat-
eral basal ganglia hyperperfusion (Newton et al., 1992; Joo
et al., 2004). With SPM group analysis, we have identified
the most consistently involved regions for a specified ictal
behavior in groups of patients. These cortical and subcorti-
cal changes are individual to each ictal symptomatology and
provide us with further insight into the neuroanatomic net-
work underlying some of the clinical signs observed during
a seizure.
Acknowledgment
This work was supported in part by University of Sydney Postgraduate
Award, Millennium Institute Stipend, and Pfizer Neuroscience Research
Grant to Dr Chong H Wong.
Disclosure
Dr. Armin Mohamed, Dr. George Larcos, Ms. Rochelle McCredie,
Dr. Ernest Somerville, and Dr. Andrew Bleasel report no disclosures. We
confirm that we have read the Journal’s position on issues involved in
ethical publication and affirm that this report is consistent with those
guidelines.
References
Andersen AR. (1989) 99mTc-D,L-hexamethylene-propyleneamine oxime
(99mTc-HMPAO): basic kinetic studies of a tracer of cerebral blood
flow. Cerebrovasc Brain Metab Rev 1:288–318.
Baron JC, Bousser MG, Comar D, Castaigne P. (1981) ‘‘Crossed cerebellar
diaschisis’’ in human supratentorial brain infarction. Trans Am Neurol
Assoc 105:459–461.
Blanke O, Spinelli L, Thut G, Michel CM, Perrig S, Landis T, Seeck M.
(2000) Location of the human frontal eye field as defined by electrical
cortical stimulation: anatomical, functional and electrophysiological
characteristics. Neuroreport 11:1907–1913.
Bleasel A, Kotagal P, Kankirawatana P, Rybicki L. (1997) Lateralizing
value and semiology of ictal limb posturing and version in temporal
lobe and extratemporal epilepsy. Epilepsia 38:168–174.
Bleasel A, Luders HO. (2000) Tonic seizures. In Luders HO, Noachtar S
((Eds)) Epileptic seizures: pathophysiology and clinical semiology.
Churchill Livingstone, Philadelphia, pp. 389–411.
Bohnen NI, O’Brien TJ, Mullan BP, So EL. (1998) Cerebellar changes in
partial seizures: clinical correlations of quantitative SPECT and MRI
analysis. Epilepsia 39:640–650.
Brodal A. (1972) Cerebrocerebellar pathways. Anatomical data and some
functional implications. Acta Neurol Scand Suppl 51:153–195.
Epilepsia, 51(10):2131–2139, 2010
doi: 10.1111/j.1528-1167.2010.02723.x
Chauvel P, Trottier S, Vignal JP, Bancaud J. (1992) Somatomotor seizures
of frontal lobe origin. Adv Neurol 57:185–232.
Commission. (1989) Proposal for revised classification of epilepsies
and epileptic syndromes. Commission on Classification and Terminol-
ogy of the International League Against Epilepsy. Epilepsia 30:389–
399.
Cui D-M, Yan Y-J, Lynch JC. (2003) Pursuit subregion of the frontal eye
field projects to the caudate nucleus in monkeys. J Neurophysiol
89:2678–2684.
Foerster O. (1931) The cerebral cortex in man. Lancet 218:309–312.
Godoy J, Luders H, Dinner DS, Morris HH, Wyllie E. (1990) Versive eye
movements elicited by cortical stimulation of the human brain. Neurol-
ogy 40:296–299.
Joo EY, Hong SB, Lee EK, Tae WS, Kim JH, Seo DW, Hong SC, Kim S,
Kim MH. (2004) Regional cerebral hyperperfusion with ictal
dystonic posturing: ictal-interictal SPECT subtraction. Epilepsia 45:
686–689.
Laich E, Kuzniecky R, Mountz J, Liu HG, Gilliam F, Bebin M, Faught E,
Morawetz R. (1997) Supplementary sensorimotor area epilepsy.
Seizure localization, cortical propagation and subcortical activation
pathways using ictal SPECT. Brain 120 (Pt 5):855–864.
Laplane D, Talairach J, Meininger V, Bancaud J, Orgogozo JM. (1977)
Clinical consequences of corticectomies involving the supplementary
motor area in man. J Neurol Sci 34:301–314.
Leichnetz GR, Gonzalo-Ruiz A. (1996) Prearcuate cortex in the cebus mon-
key has cortical and subcortical connections like the macaque frontal
eye field and projects to fastigial-recipient oculomotor-related brain-
stem nuclei. Brain Res Bull 41:1–29.
Lim SH, Dinner DS, Pillay PK, Luders H, Morris HH, Klem G, Wyllie E,
Awad IA. (1994) Functional anatomy of the human supplementary
sensorimotor area: results of extraoperative electrical stimulation.
Electroencephalogr Clin Neurophysiol 91:179–193.
Luders H, Lesser RP, Dinner DS, Morris HH, Hahn JF, Friedman L. (1987)
Chronic intracranial recording and stimulation with subdural elec-
trodes. In Engel J Jr (Ed) Surgical Treatment of the Epilepsies. Raven
Press, New York, pp. 297–321.
Luders H, Acharya J, Baumgartner C, Benbadis S, Bleasel A, Burgess R,
Dinner DS, Ebner A, Foldvary N, Geller E, Hamer H, Holthausen H,
Kotagal P, Morris H, Meencke HJ, Noachtar S, Rosenow F, Sakamoto
A, Steinhoff BJ, Tuxhorn I, Wyllie E. (1998) Semiological seizure
classification. Epilepsia 39:1006–1013.
McNally KA, Paige AL, Varghese G, Zhang H, Novotny EJ Jr, Spencer SS,
Zubal IG, Blumenfeld H. (2005) Localizing value of ictal-interictal
SPECT analyzed by SPM (ISAS). Epilepsia 46:1450–1464.
Newton MR, Berkovic SF, Austin MC, Reutens DC, McKay WJ, Bladin
PF. (1992) Dystonia, clinical lateralization, and regional blood flow
changes in temporal lobe seizures. Neurology 42:371–377.
Noachtar S, Peters AS. (2009) Semiology of epileptic seizures: a critical
review. Epilepsy Behav 15:2–9.
Nobili L, Cossu M, Mai R, Tassi L, Cardinale F, Castana L, Citterio A,
Sartori I, Lo Russo G, Francione S. (2004) Sleep-related hyperkinetic
seizures of temporal lobe origin. Neurology 62:482–485.
Pastor J, Dominguez-Gadea L, Sola RG, Hernando V, Meilan ML, Dios
ED, Martinez-Chacon JL, Martinez M. (2008) First true initial ictal
SPECT in partial epilepsy verified by electroencephalography. Neuro-
psychiatr Dis Treat 4:305–309.
Penfield W, Welch K. (1951) The supplementary motor area of the cerebral
cortex; a clinical and experimental study. AMA Arch Neurol Psychiatry
66:289–317.
Rasband WS. (1997–2009) ImageJ. U. S. National Institutes of Health,
Bethesda, Maryland, U.S.A. Available at: http://rsb.info.nih.gov/ij/.
Rheims S, Ryvlin P, Scherer C, Minotti L, Hoffmann D, Guenot M,
Mauguiere F, Benabid AL, Kahane P. (2008) Analysis of clinical
patterns and underlying epileptogenic zones of hypermotor seizures.
Epilepsia 49:2030–2040.
Salloway SP, Malloy PF, Duffy JD. (2001) The Frontal Lobes and Neuro-
psychiatric Illness. American Psychiatric Publishing, Inc., Washington,
DC.
Schlaug G, Antke C, Holthausen H, Arnold S, Ebner A, Tuxhorn I,
Jancke L, Luders H, Witte OW, Seitz RJ. (1997) Ictal motor signs
and interictal regional cerebral hypometabolism. Neurology 49:341–
350.

Shin WC, Hong SB, Tae WS, Kim SE. (2002) Ictal hyperperfusion patterns
according to the progression of temporal lobe seizures. Neurology
58:373–380.
So EL. (2006) Value and limitations of seizure semiology in localizing
seizure onset. J Clin Neurophysiol 23:353–357.
Spencer SS. (2002) Neural networks in human epilepsy: evidence of and
implications for treatment.[see comment]. Epilepsia 43:219–227.
Van Paesschen W, Dupont P, Sunaert S, Goffin K, Van Laere K. (2007)
The use of SPECT and PET in routine clinical practice in epilepsy. Curr
Opin Neurol 20:194–202.
Wiesendanger M. (1986) Recent developments in studies of the supple-
mentary motor area of primates. Rev Physiol Biochem Pharmacol
103:1–59.
Won JH, Lee JD, Chung TS, Park CY, Lee BI. (1996) Increased contralat-
eral cerebellar uptake of technetium-99m-HMPAO on ictal brain
SPECT. J Nucl Med 37:426–429.
Woolsey CN, Settlage PH, Meyer DR, Sencer W, Pinto Hamuy T, Travis
AM. (1952) Patterns of localization in precentral and ‘‘supplementary’’
motor areas and their relation to the concept of a premotor area. Res
Publ Assoc Res Nerv Ment Dis 30:238–264.
Wyllie E, Luders H, Morris HH, Lesser RP, Dinner DS. (1986) The lateral-
izing significance of versive head and eye movements during epileptic
seizures. Neurology 36:606–611.
2139
SPECT Patterns and Seizure Semiology
Zentner J, Hufnagel A, Pechstein U, Wolf HK, Schramm J. (1996) Func-
tional results after resective procedures involving the supplementary
motor area. J Neurosurg 85:542–549.
Supporting Information
Additional Supporting Information may be found in the
online version of this article:
Figure S1. SPM output for versive seizure subgroup.
Figure S2. SPM output for bilateral asymmetric tonic sei-
zure subgroup.
Figure S3. SPM output for hypermotor seizure subgroup.
Please note: Wiley-Blackwell is not responsible for the
content or functionality of any supporting information sup-
plied by the authors. Any queries (other than missing mate-
rial) should be directed to the corresponding author for the
article.
Epilepsia, 51(10):2131–2139, 2010
doi: 10.1111/j.1528-1167.2010.02723.x