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Dopa-responsive dystonia due to mild tyrosine hydroxylase deficiency.

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Does Alcohol Cancel Static
Vestibular Compensation?
Vera C. Zingler, MD, Michael Strupp, MD,
Siegbert Krafczyk, PhD, Cornelia Karch,
and Thomas Brandt, MD, FRCP
Acute alcohol intoxication is accompanied by the otoneurological signs of spinocerebellar and vestibulocerebellar ataxia,
positional alcohol nystagmus, and ocular motor abnormalities, such as saccadic pursuit and gaze-evoked nystagmus.
Some of these ocular motor disturbances possibly result from
a transient alcohol-induced dysfunction of the vestibulocerebellar flocculus loop. On the cellular level, ethanol may alter
neural activity by several mechanisms, including direct action
on neurotransmitter-gated ion channels that lead, for example, to inhibition of N-methyl-D-aspartate and enhancement
of GABA receptors.1
Incidental reports on patients with centrally compensated
unilateral peripheral vestibular failure (UVF) mention reduced tolerance to low doses of alcohol. This suggests that
alcohol might cancel an already compensated persisting
UVF.2 Indeed, animal studies on compensated hemilabyrinthectomized cats have supported this assumption by showing that intravenously administered alcohol temporarily
caused a recurrence of the initial spontaneous nystagmus
To determine if alcohol neutralizes central vestibular compensatory mechanisms under static conditions in humans in
a similar way, we examined 12 patients (10 men; mean age
59.1 ⫾ 16.5 years; range, 23–74 years) with compensated
persisting UVF due to vestibular neuritis that had manifested
3 to 69 months before the study. Only patients with unilateral hyporesponsiveness or unresponsiveness (⬍25% according to Jongkees’ vestibular paresis formula) to caloric irrigation of the affected ear participated in the study after giving
their informed consent. Eight patients exhibited complete
unresponsiveness and four showed hyporesponsiveness. Be-
fore alcohol intake, none of the patients showed SPN during
video-oculographic recordings with eyes open in the dark.
Dynamic vestibular function, as assessed with the head thrust
maneuver (Curthoys–Halmagyi), was not tested.
In analogy to an earlier study on positional alcohol nystagmus,4 patients ingested 0.8g alcohol/kg body weight
(2.5ml vodka/kg body weight) to reach alcohol blood levels
of approximately 0.1%. To evaluate the effects of alcohol on
ocular motor, vestibulospinal, and perceptional systems in
patients with compensated vestibular neuritis, we performed
the following measures before and 30 minutes after alcohol
intake: (1) a neurological examination focusing on possible
alcohol-induced ocular motor disturbances such as saccadic
pursuit and gaze-holding deficit, (2) two-dimensional videooculography in complete darkness (to detect SPN); (3) laser
scanning ophthalmoscopy to determine ocular torsion (in degrees)5; (4) posturography on a foam-padded Kistler platform with the eyes open in darkness to assess total sway path
values (in m/min), and (5) adjustments of subjective visual
vertical under static and dynamic conditions (in degrees).5
Compared with the neurological examination before ingestion (which showed normal findings), alcohol caused saccadic horizontal and vertical pursuit in 10 of 12 patients and
a horizontal gaze-evoked nystagmus in 8 of 12. Spontaneous
nystagmus did not recur in any of the 12 patients after ingesting alcohol. No significant displacements of ocular torsion or subjective visual vertical, neither under static nor under dynamic conditions, were observed (Fig 1). The total
sway path during upright stance on the force-measuring platform also did not increase; on the contrary, it even tended to
decrease after alcohol intake. Fourier analysis of the anterior/
posterior and lateral body sway exhibited a significantly reduced sway activity in the frequency spectrum 3.5 to 8Hz
( p ⬍ 0.05). This effect of alcohol on body sway might be a
result of the dose-related biphasic action of alcohol, which
either depresses or stimulates depending on its concentration
in the blood; a similar finding was reported in a previous
study on body sway patterns in healthy volunteers.6
All in all, our findings show that contrary to what is generally assumed, alcohol in the chosen doses used here did not
cause a decompensation (at the perceptional, ocular motor,
or vestibular-spinal levels) under static conditions of a compensated vestibular tone imbalance due to a persisting unilateral loss of vestibular function. On the other hand, we do
not yet know if alcohol causes a decompensation of dynamic
vestibular function as reflected in responses with the head or
body moving.
Department of Neurology, Ludwig-Maximilians University,
Klinikum Großhadern, Munich, Germany
Fig. Mean values and standard deviation of the subjective
visual vertical (SVV, in degrees), ocular torsion ipsilateral to
the lesioned side (OT, in degrees), and total sway-path values
(total-SP, in m/min) before and after alcohol. Displacement of
SVV under dynamic conditions was clockwise 14.7 ⫾ 5.0
degrees and counterclockwise 16.1 ⫾ 11.2 degrees before and
clockwise 11.6 ⫾ 5.3 and 8.2 ⫾ 10.8 degrees after ingestion
of alcohol (p ⬎ 0.05, not shown).
1. Criswell HE, Ming Z, Griffith BL, Breese GR. Comparison of
effect of ethanol on N-methyl-D-aspartate-and GABA-gated currents from acutely dissociated neurons: absence of regional differences in sensitivity to ethanol. J Pharmacol Exp Ther 2003;
2. Zee DS. The management of patients with vestibular disorders.
In Barber HO, Sharpe JA, eds. Vestibular disorders. Chicago:
Year Book 1988:254 –274.
© 2003 American Neurological Association
Published by Wiley-Liss, Inc., through Wiley Subscription Services
3. Berthoz A, Young L, Oliveras F. Action of alcohol on vestibular
compensation and habituation in the cat. Acta Otolaryngol
4. Fetter M, Haslwanter T, Bork M, Dichgans J. New insights into
positional alcohol nystagmus using three-dimensional eyemovement analysis. Ann Neurol 1999;45:216 –223.
5. Dieterich M, Brandt T. Ocular torsion and tilt of subjective visual vertical are sensitive brainstem signs. Ann Neurol 1993;33:
6. Nieschalk M, Ortmann C, West A, et al. Effects of alcohol on
body-sway patterns in human subjects. Int J Legal Med 1999;
DOI: 10.1002/ana.10780
The R98Q Variation in DJ-1 Represents a
Rare Polymorphism
Katja Hedrich, PhD,1,2 Nora Schäfer, BS,1,2
Robert Hering, PhD,3 Johann Hagenah, MD,1
Andrea J. Lanthaler, MA,4 Eberhard Schwinger, MD,2
Patricia L. Kramer, PhD,5 Laurie J. Ozelius, PhD,6
Susan B. Bressman, MD,7 Giovanni Abbruzzese, MD,8
Paolo Martinelli, MD,9 Vladimir Kostic, MD,10
Peter P. Pramstaller, MD,11 Peter Vieregge, MD,1,12
Olaf Riess, PhD,3 and Christine Klein, MD1,2
We read with great interest the recent article by Hague et al.
confirming the occurrence of DJ-1 mutations in patients
with early-onset Parkinson’s disease (EOPD).1 DJ-1
(PARK7) recently was identified as the second gene associated with recessively inherited EOPD in two consanguineous
families with homozygous mutations with an age at onset
(AAO) between 27 and 40 years.2 Hague and colleagues extended the role of DJ-1 mutations to nonconsanguineous
EOPD families, demonstrating compound-heterozygous in
one patient (AAO ⫽ 24 years) and single heterozygous mutations in four index patients.1 One single heterozygous missense mutation (293G3 A; R98Q) was found recurrently in
three unrelated patients with an AAO between 39 and 49
years. The 293G3 A carriers were of very different ethnic
background, rendering a common founder unlikely and suggesting the possibility of a polymorphism. However, no data
are reported on the frequency of 293G3 A in controls.
To evaluate the role of the 293G3 A sequence variation
in our own patient and control population, we investigated
300 mainly European EOPD patients and 99 ethnically
matched healthy controls for the presence of the 293G3 A
change. Patients (173 men and127 women) had an age at
onset ranging from 9 to 50 years (mean, 38.3 ⫾ 7.2 years).
Mutational analysis was performed by denaturing highperformance liquid chromatography analysis of exon 5 in patients and by restriction fragment length polymorphism analysis with MspI in the control group.
We detected the 293G3 A substitution in 10 patients in
the heterozygous state (1.67% of chromosomes) and in two
controls (one heterozygous and one homozygous; 1.52% of
chromosomes). Thus, the frequency of this substitution does
not differ significantly between patients and controls ( p ⬎
0.05). Second, the frequency of the substitution 293G3 A is
present in more than 1% of control chromosomes and thus
has to be considered a polymorphism.3
In addition, Hague and colleagues reported a second sin-
gle base pair substitution in exon 5 in a Latino patient
(310G3 A, A104T; AAO ⫽ 35 years).1 In our screen, this
alteration was not detected in any of our mostly European
patients. Although it cannot be excluded that this substitution was undetectable by our denaturing high-performance
liquid chromatography assay or that it is underrepresented in
Europeans, our data support the idea that this substitution is
not a polymorphism.
In conclusion, our results argue that the R98Q variant
represents a polymorphism in DJ-1. The relevance of this
polymorphism as a possible susceptibility factor for PD and
the role of the A104T alteration remain to be established in
association and functional studies.
This work was supported by the German Research Foundation (Kl1134/2-2), PDF/NPF (K.H., C.K.), a Research Grant of the University of Lübeck (J03-2003; K.H.), and the FORTÜNE program
of the medical faculty of the University of Tübingen (R.H., O.R.).
Departments of 1Neurology and 2Human Genetics, University
of Lübeck, Lübeck; 3Department of Medical Genetics,
University of Tübingen, Tübingen, Germany; 4Department of
Hematology, Regional General Hospital, Bolzano, Italy;
Department of Neurology, Oregon Health Sciences University,
Portland, OR; 6Department of Molecular Genetics, Albert
Einstein College of Medicine, Bronx; 7Department of
Neurology, Beth Israel Medical Center, New York, NY;
Department of Neurological Sciences and Vision, University
of Genova, Genova; 9Department of Neurological Sciences,
University of Bologna, Bologna, Italy; 10Department of
Neurology, School of Medicine, University of Belgrade,
Belgrade, Serbia; 11Department of Neurology, Regional
General Hospital, and EURAC-Research, Genetic Medicine,
Bolzano, Italy; and 12Hospital of Lippe-Lemgo,
Lemgo, Germany
1. Hague S, Rogaeva E, Hernandez D, et al. Early-onset Parkinson’s disease caused by a compound heterozygous DJ-1 mutation. Ann Neurol 2003;54:271–274.
2. Bonifati V, Rizzu P, van Baren MJ, et al. Mutations in the DJ-1
gene associated with autosomal recessive early-onset parkinsonism. Science 2003;299:256 –259.
3. Passarge E. Color atlas of genetics. New York: Thieme Medical
Publishers, 1995.
DOI: 10.1002/ana.10816
E. Whitney Evans, BA, Stephen Hague, PhD,
and Andrew Singleton, PhD
We thank Hedrich and colleagues for their interest in our
article on DJ-1 mutations and Parkinson’s disease. Their
data are consistent with our initial suggestion that R98Q
may indeed be a benign variant. Subsequent to acceptance
of our article, we sought to ascertain the population frequency of this variant, which was identified in three ethnically disparate patients, in the publicly available human genome diversity panel.1 Here, we provide data that extend
Annals of Neurology
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Table. Regional Distribution of DJ-1 R98Q Variants in the CEPH Human Genome Diversity Panel (frequency)
Regional Group
Middle East
Central/South Asia
East Asia
127 (0.993)
141 (0.950)
122 (0.976)
157 (0.981)
244 (0.992)
37 (1.000)
108 (1.000)
936 (0.982)
1 (0.007)
8 (0.050)
3 (0.024)
2 (0.013)
2 (0.008)
16 (0.017)
1 (0.006)
1 (0.001)
255 (0.996)
290 (0.973)
247 (0.988)
316 (0.987)
490 (0.995)
74 (1.000)
216 (1.000)
1888 (0.991)
1 (0.004)
8 (0.027)
3 (0.012)
4 (0.013)
2 (0.005)
18 (0.009)
our original observations and those of Hedrich and colleagues.
The R98Q polymorphism was assayed by polymerase
chain reaction amplification with primer pairs specific for
exon 5 as previously described.2 The resulting product was
digested with restriction enzyme HapII and electrophoresed
on a 2% agarose gel. We demonstrate that the 98Q variant is
present in all major populations bar Oceania and Central
and South America. The frequency of the Q variant was
highest in the European population at a comparable rate to
that within our original Parkinson’s disease (PD) cohort and
the series described by Hedrich and colleagues. Notably, we
identified a 98Q homozygous individual from Central/South
Asia (Pathan population Pakistan; variant confirmed by sequencing). It is unlikely that this individual has or will have
young-onset PD; however, note that this is a cohort of samples designed to represent ethnically divergent populations
and not a neurological control series.
Taking an allelic frequency of 0.027 for the Q variant,
one would expect to see one 98Q homozygote for every
5,500 individuals in the European population, this mutation therefore would account for the majority of youngonset PD3 a fact that has not been borne out by mutational
analysis of DJ-1. Hence, it is implausible that this variant
is of pathogenic relevance. These data strongly support
our initial supposition and the view of Hedrich and colleagues that R98Q should be considered a benign polymorphism.
Molecular Genetics Section, Laboratory of Neurogenetics,
National Institute on Aging, National Institutes of Health,
Bethesda, MD
1. Cann HM, de Toma C, Cazes L, et al. A human genome diversity cell line panel. Science 2002;296:261–262
2. Hague S, Rogaeva E, Hernandez D, et al. Early-onset Parkinson’s disease caused by a compound heterozygous DJ-1 mutation. Ann Neurol 2003;54:271–274.
3. Van Den Eeden SK, Tanner CM, Bernstein AL, et al. Incidence
of Parkinson’s disease: variation by age, gender, and race/
ethnicity. Am J Epidemiol 2003;157:1015–1022.
DOI: 10.1002/ana.10817
Annals of Neurology
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Calpain 3 Deficiency in Quail Eater’s Disease
Olimpia Musumeci, MD,1 Mohammed Aguennouz, PhD,1
Rachele Cagliani, PhD,2 Giacomo Pietro Comi, MD,2
Anna Ciranni, PhD,1 Carmelo Rodolico, MD,1
Corrado Messina, MD,1 Giuseppe Vita, MD,1
and Antonio Toscano, MD1
A rhabdomyolysis outbreak after quail meat ingestion (Quail
Eater’s disease [QED]) have been reported in individuals
from Algeria, Southern France, Spain, and Greece but never
in Italy.1 This disease, characterized by myalgia, stiffness,
cramps, and myoglobinuria may occur 6 to 8 hours after a
meal, in spring or autumn when quails migrate from Northern Africa to Europe or vice versa. It is benign with fast
recovery and good outcome; however, some fatal cases have
been described.1 Its etiopathogenesis is unknown, but it has
been suggested that human skeletal muscle is particularly
prone to toxic seeds ingested by quails (Conium maculatum
or water hemlock, Galeopsis ladanum), or to metabolites accumulated during the migration journey.1,2
Two unrelated patients (a 40-year-old woman [F] and a
31-year-old man [M]) from northern Sicily (Italy) were examined in spring 1998 and 2001, respectively, because of
sudden onset of nausea, vomiting, muscle aches and cramps,
stiffness, and mild proximal weakness, 8 to 10 hours after a
meal with wild quails. Clinical examination showed diffuse
pain on muscle palpation and slight proximal weakness with
high serum creatine kinase (CK) level (F, 33,000IU/L; M,
13,500IU/L) and myoglobinuria were present. Electromyography was normal. Hydration and diuretics were administrated with a full recovery in about a week. A clinical
follow-up at 6 and 12 months was normal.
A day after admission, both patients underwent a muscle
biopsy showing only a mild lipid storage in one case. To rule
out a muscle metabolic disorder, we performed an extensive
biochemical analysis of mitochondrial, glycogenolytic, glycolytic, and lipid pathways as well myoadenylate deaminase activity in both patients with normal results.
Immunohistochemistry showed normal expression of dystrophin, sarcoglycans, caveolin 3, dysferlin, and merosin.
Western blot analysis showed a calpain 3 abnormal pattern
in both patients, with a marked decrease of 60kDa and
94kDa bands and a slight reduction of the 30kDa band
(Fig). The overall profile of calpain 3 bands did not indicate
protein degradation. Molecular genetic analysis excluded calpain 3 gene (CAPN3) pathogenic mutations.
We postulate that an unknown toxin, present in quail
meat, could have induced a calpain 3 reduction in human
muscles, triggering acute muscular damage. An experimental
design using animals fed with various toxic seeds is needed to
elucidate the role of calpain and/or other muscle proteins in
the pathogenesis of QED.
Department of Neurosciences, Psychiatry, and Anaesthesiology,
University of Messina, Messina; and 2Dino Ferrari Center,
Department of Neurosciences, University of Milan, Scientific
Institute for Research, Hospitalization, and Health Care,
Milan, Italy
1. Papadimitriou A, Hadjigeorgiou GM, Tsairis P, et al. Myoglobinuria due to quail poisoning. Eur Neurol 1996;36:142–
2. Aparicio R, Onate JM, Arizcun A, et al. [Epidemic rhabdomyolysis due to the eating of quail. A clinical, epidemiological and
experimental study]. Med Clin (Barc) 1999;112:143–146.
3. Anderson LV, Harrison RM, Pogue R, et al. Secondary reduction in calpain 3 expression in patients with limb girdle muscular
dystrophy type 2B and Miyoshi myopathy (primary dysferlinopathies). Neuromuscul Disord 2000;10:553–559.
4. Hackman P, Vihola A, Haravuori H, et al. Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene
encoding the giant skeletal-muscle protein titin. Am J Hum
Genet 2002; 71:492–500.
DOI: 10.1002/ana.10821
Dopa-Responsive Dystonia Due to Mild Tyrosine
Hydroxylase Deficiency
Fig. Calpain 3 Western blot analysis with monoclonal antibody 3d/2C4 (A) and with monoclonal antibody 3c/12A2 (B).
C1 and C2 ⫽ controls 1 and 2. 1 ⫽ Case 1; 2 ⫽ case 2.
QED etiopathogenesis is unclear. Poisonous seeds were indicated as responsible for muscle damage but doubts still exist about their toxicity. Papadimitriou and colleagues studied
10 Greek patients with QED: muscle biochemical investigations were negative, and they concluded that a major factor
contributing to quail poisoning might have been toxic.1 In
1999, Aparicio and colleagues reported 20 patients with
rhabdomyolysis: G. Ladanum seed were isolated from the
quail crops. Rats experimentally fed with quail meat intoxicated by G. Ladanum developed hyperCKemia.2
Calpain 3 is primarily deficient in limb-girdle muscular
dystrophy 2A, often caused by mutations of the CAPN3
gene, whereas a secondary deficiency was reported in dysferlinopathies, titinopathies, facioscapulohumeral muscular dystrophy, and idiopathic hyperCKemia.3,4
In these first two cases of QED in Italy, there was reduced
calpain 3 expression with absence of pathogenic mutation of
the CAPN3 gene, suggesting a secondary reduction of the
protein. Interestingly, calpain 3 deficiency was spatial, but it
was demonstrated in muscle with no significant morphological changes.
Yoshiaki Furukawa, MD,1 Stephen J. Kish, PhD,2
and Stanley Fahn, MD3
Clinical features of autosomal recessive tyrosine hydroxylase
(TH) deficiency were summarized recently by Hoffmann and
colleagues.1 The authors emphasize that there have been no
patients with TH deficiency showing a complete resolution
of symptoms by L-dopa treatment, except for one compound
heterozygote for TH mutations, and conclude that TH deficiency causes progressive encephalopathy and “dopanonresponsive dystonia.” To our knowledge, however, six
genetically confirmed patients with TH deficiency from
four unrelated families have been reported to respond completely to L-dopa therapy, including two brothers with typical dopa-responsive dystonia (DRD) originally described
by Castaigne and colleagues in 1971.2,3 Thus, TH was considered to be one of the causative genes for DRD, and clinical phenotypes due to TH mutations reported were divided
into DRD (the mild form of TH deficiency) and infantile
parkinsonism with motor delay (the severe form of TH deficiency).2,4
A clinical syndrome, DRD is characterized by childhoodonset dystonia and a dramatic and sustained response to low
doses of L-dopa. Approximately 60% of patients with DRD,
including apparently sporadic cases, are caused by dominantly inherited heterozygous mutations in the coding region
of GCH1 that encodes GTP cyclohydrolase I (GTPCH), the
Annals of Neurology
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January 2004
first enzyme in the biosynthetic pathway for tetrahydrobiopterin (the essential cofactor for TH).2 Some clinical features
of the severe form of TH deficiency (eg, developmental motor delay, truncal hypotonia, rigidity of extremities, hypokinesia, oculogyric crises, and the onset at younger than 6
months) can be found in compound heterozygotes for
GCH1 mutations.2,5 It is assumed that a relatively small percentage of DRD patients has TH mutations. However, because a positive result of TH analysis could provide information on prognosis (ie, DRD vs. neurodegenerative
diseases), an effort to find TH mutations in GCH1 mutation–negative DRD patients is indispensable. In both
brothers reported by Castaigne and colleagues,3 a sustained
response to L-dopa treatment without any motor adverse
effects for more than 30 years has been confirmed (see references in Furukawa2).
A wide range of phenotypes has been found in patients
associated with GCH1 mutations (from GTPCH-deficient
DRD to GTPCH-deficient hyperphenylalaninemia2,5), and
this also may be true for TH mutations (from TH-deficient
DRD to a lethal metabolic disorder1,2). Although further accumulation of genetically confirmed patients with TH deficiency is necessary to establish the major clinical characteristics, we believe that the DRD phenotype should not be
missed out of the spectrum of TH deficiency.
Movement Disorders Research Laboratory and 2Human
Neurochemical Pathology Laboratory, Centre for Addiction
and Mental Health-Clarke Division, Toronto, Ontario,
Canada; and Department of Neurology, Columbia
Presbyterian Medical Center, New York, NY
1. Hoffmann GF, Assmann B, Bräutigam C, et al. Tyrosine hydroxylase deficiency causes progressive encephalopathy and
dopa-nonresponsive dystonia. Ann Neurol 2003;54(suppl 6):
S56 –S65.
2. Furukawa Y. Genetics and biochemistry of dopa-responsive
dystonia: significance of striatal tyrosine hydroxylase protein loss.
Adv Neurol 2003;91:401– 410.
3. Castaigne P, Rondot P, Ribadeau-Dumas JL, Saı̈d G. Affection
extrapyramidale évoluant chez deux jeunes frères: effects remarquables du traitement par la L-dopa. Rev Neurol 1971;124:
4. Fahn S, Bressman SB, Marsden CD. Classification of dystonia.
Adv Neurol 1998;78:1–10.
5. Furukawa Y, Kish SJ, Bebin EM, et al. Dystonia with motor
delay in compound heterozygotes for GTP-cyclohydrolase I gene
mutations. Ann Neurol 1998;44:10 –16.
DOI: 10.1002/ana.10820
Annals of Neurology
Fig 4. Experiment 4. Reaction times (RTs) grouped according
to the degree of motor recovery in patients with poor (shaded
area to left) or good motor recovery (unshaded area). Note
that in both recovery groups, only contralateral TMS stimulation led to significant RT delays compared with sham. The
delay elicited by stimulation of the lesioned hemisphere in the
paretic hand was more prominent in patients with good recovery than in those with poor recovery (shaded area). **p ⬍
0.01; *p ⬍ 0.05.
The authors appreciate acknowledgment of this clarification.
Herzog AG, Coleman AE, Jacobs AR, Klein P,
Friedman MN, Drislane FW, Ransil BJ, Schomer
DL. Interictal EEG dicharges, reproductive hormones, and menstrual disorders in epilepsy. Ann
Neurol 2003;54:625– 637 (November 2003).
The acknowledgements section was erroneously deleted from this article. The section is printed below.
This paper is supported by National Institutes of
Health (NIH) Grants NS33189 (to Beth Israel Deaconness Medical Center) and a NIH General Clinical
Research Centers Grant (#MO1-RR01032, A.G.H.).
The publisher regrets this oversight.
Corrections and Clarifications
Werhahn KJ, Conforto AB, Kadom N, Hallett M,
Cohen LG. Contribution of the ipsilateral motor
cortex to recovery after chronic stroke. Ann Neurol
2003:54;464 – 472 (October 2003).
The correct version of Figure 4 did not appear in the
published article. The corrected Figure 4, with the legend, is printed below.
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January 2004
Fujioka M, Taoka T, Matsuo Y, Mishima K, Ogoshi K, Kondo Y, Tsuda M, Fujiwara M, Asano T,
Sakaki T, Miyasaki A, Park D, Siesjö BK. Magnetic
resonance imaging shows delayed ischemic striatal
neurodegeneration. Ann Neurol 2003;54:732–747
(December 2003).
“P” signs indicating p values were erroneously added
to the bar representing 16 weeks in figure 6C. The
corrected figure part, with accompanying legend, is reprinted here below.
The authors appreciate acknowledgment of this clarification.
Vaurs-Barriere C, Wong K, Weibel TD, AbuAsab M, Weiss MD, Kaneski CR, Mixon T-H,
Bonavita S, Creveaux I, Heiss JD, Tsokos M, Goldin E, Quarles RH., Boespflug-Tanguy O, Schiffmann R. Insertion of mutant proteolipid protein results in missorting of myelin proteins. Ann Neurol
2003;54:769 –780 (December 2003).
Due to a production oversight, there were several errors in this article. Corrections are listed below.
Fig 6. (C) Chronological changes of the surviving neuronal
ratio (%) in the dorsolateral striatum after 15-minute MCAO
(n ⫽ 6 at each period). The surviving neuronal ratio continued to decrease over time from 4 hours (19.1 ⫾ 0.7%)
through to 16 weeks (3.2 ⫾ 0.2%) after ischemia (F[6, 35]
⫽ 47.952, p ⬍ 0.0001, one-way factorial ANOVA). *p ⬍
0.05 compared to periods of 4 hours and 3 days after ischemia; #p ⬍ 0.05 compared with periods between 7 days and
4 weeks (Tukey-Kramer test). Values indicate mean ⫾ SEM.
1. Abstract, line 5: Transcript should read ⌬ex4,
169bp (not Dex4, as printed).
2. Patients and Methods section, line 2: The father in the family pedigree was incorrectly identified: This patient is II-3 (not III-3 as printed).
3. The correct affiliation for Dr. Michael D. Weiss
is the National Institute of Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD.
4. There were several errors in Table 2; the corrected version is printed below.
5. There were errors in Figure 2C and 2D; the corrected version with the legend is printed below.
The publisher acknowledges and regrets these errors.
Table 2. Nerve Conduction Studies
Sensory Nerves
Superficial radial
Motor nerves
APB amplitude
F-wave latency
H amplitude
F-wave latency
EDB amplitude
F-wave latency
⬍61ms (adults)
⬍61ms (adults)
Abnormal values in are shown in boldface. APB ⫽ abductor pollicies brevis; EDB ⫽ extensor digitorum brevis.
Prolonged for height.
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Fig 2. (C) Schematic overview showing the position of IVS4 ⫹ 1 G 3 A mutation in the patient and the different resulting splice
forms. Donor and acceptor splice sites are indicated in capital letters. The underlined GT sequence in intron 4 corresponds to the
new splice donor site used to splice exon 4 ⫹ 10bp with exon 5. (D) Two types of mutated proteins were expressed in the patient;
one containing 178 amino acids of PLP (or 143 amino acids of DM20) with an additional 27 frameshifted amino acid sequence
(marked in black) at the C terminus, and the other containing 208 amino acids of PLP (or 173 amino acids of DM20) with an
additional 26 frameshifted amino acid sequence at the C terminus.
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