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Eastchester clapping sign A novel test of parietal neglect.

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12. Romigi A, Placidi F, Peppe A, et al. Pedunculopontine nucleus
stimulation influences REM sleep in Parkinson’s disease. Eur
J Neurol 2008;15:e64 –e65.
13. Lim AS, Lozano AM, Moro E, et al. Characterization of REMsleep associated ponto-geniculo-occipital waves in the human
pons. Sleep 2007;30:823– 827.
14. Paxinos G, Huang XF. Atlas of the human brainstem. San
Diego: Academic Press, 1995.
15. Fahn S, Elton RL, UPDRS Program Members. Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Goldstein
M, Calne DB, editors. Recent developments in Parkinson’s disease, Vol 2. Florham Park, NJ: Macmillan Healthcare
Information; 1987. p 153–163, 293–304.
16. Rechtschaffen A, Kales A. A manual of standardized techniques,
terminology, and scoring system for sleep stages of human subjects. Los Angeles: Brain Information Service, 1968.
17. Comella CL. Sleep disturbances and excessive daytime sleepiness in Parkinson disease: an overview. J Neural Transm Suppl
2006;70:349 –355.
18. Johnson MD, Miocinovic S, McIntyre CC, Vitek JL. Mechanisms and targets of deep brain stimulation in movement disorders. Neurotherapeutics 2008;5:294 –308.
19. McIntyre CC, Grill WM, Sherman DL, Thakor NV. Cellular effects of deep brain stimulation: model-based analysis
of activation and inhibition. J Neurophysiol 2004;91:
1457–1469.
Eastchester Clapping Sign: A
Novel Test of Parietal
Neglect
Lyle W. Ostrow, MD, PhD, and Rafael H. Llinás, MD
Hand clapping is a motor program mastered in infancy. Inspired by a question posed by an Eastchester High School
AP Psychology class, we present a case series of 14 patients
with hemispatial neglect who, when asked to clap, repeatedly
performed one-handed motions stopping abruptly at the
midline of the visual hemispace, as if pantomiming slapping
an invisible board. In contrast, hemiplegic patients without
neglect will reach across and clap against their plegic hands.
This phenomenon provides an easy, rapid, and unambiguous
test for neglect, applicable to patients of any ethnicity or age.
Ann Neurol 2009;66:114 –117
Recognizing neglect in the acute setting can be difficult
for physicians and laypeople. There is a need for rapid
and clear tests to better assess the presence and severity
of acute nondominant hemisphere infarction.1 Besides
the potential influence on treatment decisions, the
presence of neglect has a significant negative impact on
rehabilitation outcomes.2
Hand clapping is a bimanual motor program learned
in infancy,3,4 and ingrained in early infant-parent communication and childhood games across cultures,4 –7
and even in nonhuman primates.8 –10 Kaye and Marcus3 found that the median age at which children can
reliably imitate clapping is 11 months. The robust encoding of hand clapping involves both sensory and auditory feedback, enabling unconscious modulation of
the rhythm and timbre, such that one can recognize
one’s own clapping,11 as well as judge subtle differences in hand configuration based on the sound of another clapper.10
We investigated how patients with hemispatial neglect respond when asked to clap their hands. We
present a case series of 14 such patients who were admitted to our inpatient services with acute infarction.
We have named this distinct phenomenology the Eastchester Clapping Sign (ECS), in recognition of the
Eastchester High School students who initially posed
the question to their teacher Mr Weisman, and then
Mr Weisman to Dr Llinás, “What happens if you ask
patients with neglect to clap their hands?”
Patients and Methods
Patients were admitted to the Johns Hopkins Hospital Brain
Recovery Unit or the Johns Hopkins Bayview Medical Center Stroke Service. All patients received acute stroke evaluations by neurology staff, care based on established stroke center guidelines, and acute magnetic resonance imaging (MRI)/
magnetic resonance angiography of the brain with diffusion
imaging unless contraindicated.
The patients in this case series were collected consecutively
between October 2006 and October 2008, in an observational fashion as part of the routine clinical examination by
the authors. As such, level of alertness was the only exclusion
criterion. All patients in this series spoke English. Once we
realized that the ECS might be an interesting test for neglect,
later patients signed an institutional review board–approved
consent, and ECS evaluation has been incorporated into the
prospective neglect testing battery conducted by the laboratory of Dr Argye Hillis. Three of the patients in this series
and all patients in the ongoing prospective study signed the
institutional review board–approved consent.
ECS testing was performed as follows: (1) make sure pa-
From the Department of Neurology, Johns Hopkins School of
Medicine, Baltimore, MD.
Potential conflict of interest: Nothing to report.
Address correspondence to Dr Llinás, Associate Professor of Neurology, Director of Clinical Services Johns Hopkins-Bayview Neurology, Co-Director Neurology Residency Johns Hopkins Medical
Center, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, B122b, Baltimore, MD 21224. E-mail: rllinas1@jhmi.edu
Received Oct 25, 2008, and in revised form Jan 28, 2009. Accepted
for publication Jan 30, 2009.
114
© 2009 American Neurological Association
Published online Mon 00, 2009, in Wiley InterScience
(www.interscience.wiley.com). DOI: 10.1002/ana.21666
hand; and UTA ⫽ unable to assess, that is, does not follow
the command; you can try pantomime.
Fig 1. Diffusion- (left) and perfusion-weighted (right) magnetic resonance imaging scans for a patient described in the
Table, demonstrating a right parietal perfusion deficit at the
time when the patient exhibited an Eastchester Clapping Sign
grade 2 (ECS-2) clap.
tient’s arms and hands are both down at their sides; and (2)
ask patient to clap his or her hands. Grading was established
as follows: ECS-2 ⫽ one-handed clap, respects midline;
ECS-1 ⫽ searches in the contralateral hemispace for the
other hand; ECS-0 ⫽ reaches over to clap against the plegic
Results
All 14 patients described in this series were righthanded. Twelve of 14 patients had an initial ECS-2
and new right-hemisphere strokes involving the parietal
lobe on MRI (ie, with restricted diffusion). One of the
remaining two patients was initially graded ECS-1, and
then worsened to ECS-2 after bleeding into a large
right-hemisphere infarct. The other patient had a
perfusion-dependent ECS, such that she fluctuated between ECS-2 and ECS-0 with changes in blood pressure. Her MRI confirmed a right parietal perfusion
deficit without infarction (Fig 1).
The persistence of the ECS varied. Most patients
went through a progression over the first few days.
They initially respected the midline absolutely, then
started searching for the other hand over the next 1 to
2 days, and eventually would find it (Fig 2). Once they
found the other hand, they appeared able to repeat
Table. Patients Included in Case Series
Age
Sex
Initial ECS
Grade
Details
67
M
2
Large (almost entire) R MCA infarct; ECS-1 by second day, ECS-0 by third day
74
M
2
Large (posterior and middle) R MCA infarct; one week later, could follow command “take R
hand and touch L elbow” but still ECS-1
57
M
1
Large R MCA infarct; infarct extension with hemorrhagic transformation on second day,
worsened to ECS-2
89
F
2
R MCA (posterior frontal, anterior temporal, and insular cortex) infarct; rapidly improved to ECS1, then ECS-0 during hospital day 1
73
M
2
Large (almost entire) R MCA infarct
36
F
2
Presented with complete R MCA syndrome and CTA showing proximal MCA occlusion;
received IV t-PA and resolved to ECS-0; remaining infarct involved frontal and temporal
lobes, and basal ganglia; spared parietal lobe
58
F
2
ECS-2 with low blood pressure; ECS-0 when blood pressure increased (see Fig 1 for MRI)
48
F
2
Deep R intraparenchymal hemorrhage centered in basal ganglia and extending to
frontoparietal region
53
F
2
Right MCA and part ACA stroke; Received IV t-PA; spared most of inferior division
53
F
2
Large occipitoparietal R MCA infarct (spared most of superior division) with hemorrhagic
conversion
55
M
2
Extensive patchy R MCA infarcts, received IV t-PA without improvement, angiogram subsequently
showed complete ICA occlusion
92
F
2
Large R MCA and ACA infarct
80
F
2
R external capsule and basal ganglia infarct; perfusion-dependent examination and level of
consciousness over first day; by day 2, neglect had resolved and ECS-0 (see Fig 2 for
photographs of patient)
59
F
2
Atrial fibrillation; proximal R MCA clot; received intraarterial rt-PA at approximately 6 hours
ECS ⫽ Eastchester Clapping Sign; MCA ⫽ middle cerebral artery; ECS-1 ⫽ Eastchester Clapping Sign grade 1; ECS-0 ⫽ Eastchester
Clapping Sign grade 0; ECS-2 ⫽ Eastchester Clapping Sign grade 2; CTA ⫽ computed tomographic angiography; MRI ⫽ magnetic
resonance imaging; ACA ⫽ anterior cerebral artery; IV ⫽ intravenous; t-PA ⫽ tissue plasminogen activator; rt-PA ⫽ recombinant tissue
plasminogen activator.
Ostrow and Llinás: ECS Test of Neglect
115
Fig 2. Eastchester Clap Sign (ECS) in patient with neglect
(ECS-2, top two panels) and in the same patient the next day
with a subsequently normal clap to the plegic side (ECS-0,
bottom two panels).
finding it from then on. Patients with an ECS-2 would
often keep “clapping” even after being told to stop. If
an examiner put his or her hand up to meet the patients’, the patient would usually increase the velocity
of the clapping for a brief period and then stop.
Discussion
Many studies have demonstrated a bias of the National
Institutes of Health Stroke Scale toward left/dominanthemisphere deficits, as there is only one item on the
scale that directly assesses right middle cerebral artery
function.1,12–14 Di Legge and colleagues13 found that
patients with right-hemisphere strokes are 45% less
likely to receive recombinant tissue plasminogen activator, which they hypothesized to be due to both a
failure to recognize the symptoms resulting in prehospital delay, as well as the lack of standardized scores for
neglect. If neglect was recognized in these patients,
there was a twofold increase in the likelihood of receiving recombinant tissue plasminogen activator.13 Strategies suggested to improve the recognition and assessment of neglect include adjusting the weighting of the
current National Institutes of Health Stroke Scale
items,14 using alternative rapid bedside tests and the
inclusion (when possible) of perfusion-weighted MRI
in treatment algorithms,1 and teaching the signs of neglect as part of community stroke education efforts.13
We believe the ECS may represent an ideal screening
test for neglect in the acute setting. It takes less than
30 seconds to administer and is unambiguous (and
rather dramatic), thus easily recognizable by physicians
and laypersons. All patients we have observed without
neglect syndromes (ie, left middle cerebral artery infarcts) are ECS-0. In many cases, the sign does not
appear to persist after the first 1 to 2 days. However, it
116
Annals of Neurology
Vol 66
No 1
July 2009
appears to be a consistent finding in the acute period,
that is, on initial presentation to the hospital. Prospective investigation of the sensitivity, persistence, and exact localization with larger patient numbers is under
way. Of note, the patient illustrated in Figure 1 provides some indication of sensitivity, as she exhibited an
ECS-2 clap that accompanied a perfusion deficit without infarction. Other unanswered questions include
whether the ECS is seen in left-handed or ambidextrous patients.
The ECS can be tested in patients from any cultural
background and even in pediatric populations. As an
example, we evaluated an 11-year-old boy with trisomy
21, bilateral moyamoya, and significant cognitive deficits, who presented with an acute left middle cerebral
artery infarct and hemiplegia without neglect. In this
particular patient, more classic testing for neglect
would have been difficult. When asked to clap, the
young patient smiled, reached across his body with his
unaffected arm, and clapped against his plegic hand
with enthusiasm.
Neglect phenomena can be categorized by the frame
of reference and sensory modality involved. For example, the ECS would be considered a form of “egocentric” neglect, as the patient is neglecting the left hemispace defined by the midplane of the body, as opposed
to “allocentric” neglect, where the patient neglects the
left sides of individual stimuli.15,16 Recent studies have
correlated specific neglect phenomena with imaging,
pathology, and outcomes, highlighting the importance
of the clinical examination in the evaluation of acute
stroke.15 With the assistance of the laboratory of Dr
Argye Hillis, we are now prospectively studying the
ECS in acute stroke patients by adding the ECS to
their established battery of neurobehavioral testing. It is
our hope that this simple test, easy to grade and interpret, will prove to be a useful addition to the acute
evaluation of stroke patients by neurologists, as well as
nurses, emergency medical technicians, and laypeople.
We thank D. Weisman and his Eastchester High School AP Psychology class who initially posed the question, “What happens if
you ask patients with neglect to clap their hands?”
We also thank the Johns Hopkins Neurology residents
and attending neurologists who helped to care for these
patients, and the members of Dr A. Hillis’ laboratory
who are helping to continue this work.
References
1. Hillis AE, Wityk RJ, Barker PB, et al. Change in perfusion in
acute nondominant hemisphere stroke may be better estimated
by tests of hemispatial neglect than by the National Institutes of
Health Stroke Scale. Stroke 2003;34:2392–2396.
2. Ween JE, Alexander MP, DEsposito M, et al. Factors predictive
of stroke outcome in a rehabilitation setting. Neurology 1996;
47:388 –392.
3. Kaye K, Marcus J. Infant Imitation—the Sensory-Motor
Agenda. Dev Psychol 1981;17:258 –265.
4. Blake J, Vitale G, Osborne P, et al. A cross-cultural comparison
of communicative gestures in human infants during the transition to language. Gesture 2005;5:201–217.
5. Hubbard JA. Children’s traditional games from Birdsedge—
clapping songs and their notation. Folk Music Journal 1982;4:
246 –264.
6. Curtis M. A sailor went to sea: theme and variations (clapping
games). Folk Music Journal 2004;8:421– 437.
7. Kainz B. Zoo-clapping, a rhythm game for kindergartenchildren. Musica 1993;47:357–358.
8. Fletcher AW. Clapping in chimpanzees: evidence of exclusive
hand preference in a spontaneous, bimanual gesture. Am J Primatol 2006;68:1081–1088.
9. Fay JM. Hand-clapping in western lowland gorillas (Gorilla
Gorilla Gorilla). Mammalia 1989;53:457– 458.
10. Repp BH. The sound of two hands clapping: an exploratory
study. J Acoust Soc Am 1987;81:1100 –1109.
11. Flach R, Knoblich G, Prinz W. Recognizing one’s own
clapping: the role of temporal cues. Psychol Res 2004;69:
147–156.
12. Lyden P, Claesson L, Havstad S, et al. Factor analysis of the
National Institutes of Health Stroke Scale in patients with large
strokes. Arch Neurol 2004;61:1677–1680.
13. Di Legge S, Fang JM, Saposnik G, et al. The impact of lesion
side on acute stroke treatment. Neurology 2005;65:81– 86.
14. Gurol ME, Streib CD, Davis PH, et al. Can the NIHSS score
be adjusted to better reflect the extent of ischemia in right
MCA strokes? Ann Neurol 2008;64:S14 –S15.
15. Hillis AE, Newhart M, Heidler J, et al. Anatomy of spatial
attention: insights from perfusion imaging and hemispatial neglect in acute stroke. J Neurosci 2005;25:3161–3167.
16. Vallar G, Bottini G, Paulesu E. Neglect syndromes: the role of
the parietal cortex. Adv Neurol 2003;93:293–319.
Insulin-like Growth Factor-1
and Neurotrophin-3 Gene
Therapy Prevents Motor
Decline in an X-Linked
Adrenoleukodystrophy
Mouse Model
Roberto Mastroeni, MSc,1 Jean-Charles Bensadoun, PhD,1
Delphine Charvin, PhD,1 Patrick Aebischer, MD,1
Aurora Pujol, MD, PhD,2,3,4 and Cédric Raoul, PhD1
X-linked adrenoleukodystrophy (X-ALD) is the most common
inherited peroxisomal disorder characterized by a progressive
demyelination of the central nervous system. The marked loss
of myelin and oligodendrocytes observed in the disease
prompted us to evaluate the therapeutic potential of insulinlike growth factor-1 and neurotrophin-3, two potent inducers
of myelin formation and oligodendrocyte survival. Viral vectors engineered to produce insulin-like growth factor-1 or
neurotrophin-3 were administrated into the cerebrospinal fluid
of an X-linked adrenoleukodystrophy mouse model. We show
that viral-based, long-lasting delivery of insulin-like growth
factor-1 and neurotrophin-3 significantly halts the progression
of the disease and leads to potent protective effect against the
demyelination process.
Ann Neurol 2009;66:117–122
X-linked adrenoleukodystrophy (X-ALD) is a demyelinating disorder characterized by the accumulation of
saturated very-long-chain fatty acids in plasma, adrenal
glands, and white matter of the central nervous system.1 The defective gene, Abcd1, encodes the ALD
protein, a peroxisomal membrane adenosine triphosphate binding cassette hemitransporter, involved in the
From the 1Brain Mind Institute, Ecole Polytechnique Fédérale de
Lausanne, Lausanne, Switzerland, 2Molecular Genetics, and Institute of Neuropathology, IDIBELL, 08907 Barcelona, 3Center for
Biomedical Research on Rare Diseases (CIBERER) and 4Catalan Institution of Research and Advanced Studies (ICREA) Barcelona,
Spain.
Address correspondence to Dr Aebischer, Brain Mind Institute,
Ecole Polytechnique Fédérale de Lausanne (EPFL), SV BMI LEN,
Station 15, CH-1015 Lausanne, Switzerland. E-mail:
patrick.aebischer@epfl.ch
Current address for Dr Raoul: Institut National de la Santé et de la
Recherche Médicale, INSERM-Avenir, INMED, Marseille, France.
Potential conflict of interest: Nothing to report.
Received Oct 31, 2008, and in revised form Oct 31. Accepted for
publication Feb 13, 2009. Published online Mon 00, 2009, in
Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/
ana.21677
© 2009 American Neurological Association
117
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