Dystonia is characterized by abnormalities in the con-
trol of movement, with involuntary muscle contractions
causing twisting movements and abnormal postures1.
Dystonia represents the third most common movement
disorder in humans and comprises a large number of
clinical syndromes (for review see refs 2,3). These syn-
dromes can be roughly divided into two types, primary
Primary dystonias develop spontaneously in the
absence of any apparent cause or associated disease and
show no other neurological symptoms, except tremor
and myoclonus. Many primary dystonias have a heredi-
tary component and once the abnormal movements
appear they do not remit. Several forms of primary dys-
tonia are paroxysmal with dyskinesia and can be triggered
by the intake of specific substances, stress or repetitive
movements; they might also have choreic and epileptic
features. Early-onset primary dystonias are rare, fre-
quently have a genetic basis (TABLe 1) and can progress to
affect multiple body parts. Late-onset primary dystonias
are more common and usually focal; examples include
blepharospasm (spasms of eyelid closure), oromandibu-
lar dystonia, cervical dystonia (torticollis), laryngeal
dystonia (spastic dysphonia) and hand dystonia, such as
writer’s cramp (fIG. 1). These late-onset forms also appear
to have a hereditary predisposition and some genomic
linkage groups have been identified.
Secondary dystonias comprise syndromes in which
dystonic symptoms result from other disease states
or brain injury (for a complete list see ref. 3). The
manifestations and causes of secondary dystonias vary
widely. Over 42 hereditary disorders with associated
neurodegeneration have dystonic symptoms, including
Huntington’s disease, juvenile Parkinson’s disease, cere-
brospinal cortical atrophies, Wilson’s disease, ataxia-
telangiectasia and Rett syndrome. In addition, various
medications (for example, neuroleptics and calcium
channel blockers), toxins (for example, carbon monox-
ide and wasp sting) and lesions to the brain caused by
trauma, vascular injury, viral infection or demyelination
can cause symptoms of dystonia.
Several general themes have emerged from studies
on dystonias. First, it is clear from the secondary dys-
tonias — in which affected brain regions can be iden-
tified pathologically — that damage to multiple brain
regions can produce dystonia — most commonly the
basal ganglia (often seen in imaging studies of primary
dystonia as well), but also the thalamus, brainstem,
parietal lobe and cerebellum3. Second, due to the lack of
apparent neurodegeneration in primary dystonias, they
fall under the category of neurofunctional disorders,
which arise from microscale abnormalities of neural
connectivity, plasticity and/or synaptic regulation. This
might also be the case in some secondary dystonias as
the dystonic symptoms occur a long time after brain
injury, suggesting secondary functional changes. Third,
although primary and secondary dystonias often have
similar clinical and physiologic features, the ontogen-
esis of dystonia can involve distinct mechanisms. This
Review profiles the molecular, cellular and systems-level
*Department of Neurology
Hospital and Harvard
Medical School, Boston,
Massachusetts 02114, USA.
‡Department of Psychiatry
and Neurology and Athinoula
A. Martinos Center for
Hospital and Harvard
Medical School, Boston,
Massachusetts 02114, USA.
§Department of Neurology
and Center for
University of Alabama at
Alabama 35294, USA.
||Medical Neurology Branch,
National Institute of
Neurological Disorders and
Stroke (NINDS), Bethesda,
Maryland 20892, USA.
¶Department of Cell Biology
and Physiology, Washington
University School of Medicine,
St. Louis, Missouri 63110,
Correspondence to: X.O.B.
The pathophysiological basis of
Xandra O. Breakefield*, Anne J. Blood‡, Yuqing Li§, Mark Hallett||,
Phyllis I. Hanson¶ and David G. Standaert §
Abstract | Dystonias comprise a group of movement disorders that are characterized by
involuntary movements and postures. Insight into the nature of neuronal dysfunction has been
provided by the identification of genes responsible for primary dystonias, the characterization
of animal models and functional evaluations and in vivo brain imaging of patients with
dystonia. The data suggest that alterations in neuronal development and communication
within the brain create a susceptible substratum for dystonia. Although there is no overt
neurodegeneration in most forms of dystonia, there are functional and microstructural brain
alterations. Dystonia offers a window into the mechanisms whereby subtle changes in
neuronal function, particularly in sensorimotor circuits that are associated with motor
learning and memory, can corrupt normal coordination and lead to a disabling motor disorder.
222 | MaRcH 2008 | vOLuME 9
© 2008 Nature Publishing Group
Type of dystonia characterized
by a sudden onset of
symptoms of brief duration
followed by remission.
excessive and uncontrolled
movements, which may be
dystonic, repetitive or
involving limbs, torso or facial
muscles with a writhing,
A hereditary disease caused by
a defect in one or both alleles
of a single gene.
A disease in which a mutation
in one of two alleles for a gene
on an autosome (any
chromosome other than the X
and Y chromosomes) gives rise
to the syndrome.
Hereditary diseases in which
only some carriers of the
mutant gene are affected.
aspects of dysfunction in the dystonias, highlighting the
multiple ways in which the sensorimotor system can be
‘derailed’ in pathways involved in movement control and
Genetic mutations in dystonia
More than 14 genes have been implicated in different
monogenic dystonia syndromes, which are frequently
inherited as autosomal dominant conditions with reduced
penetrance4 (TABLe 1). This low penetrance suggests that
a ‘second hit’, such as the inheritance of other genetic
traits or environmental insults, might be involved in trig-
gering the onset of dystonic symptoms. For example, in
the case of early-onset generalized dystonia (DYT1) a
coding polymorphism in the wild-type allele has a dra-
matic effect on penetrance5 and, in some cases, the onset
of symptoms has been associated with injury, hypoxia
and viral infection6,7. Other forms of dystonia can be
triggered by emotional or physical stress; for example,
rapid onset dystonia-parkinsonism (DYT12) can appear
abruptly and persists throughout life8. Environmental
stimuli might also cause transient forms of dystonia; for
example, intake of caffeine or alcohol elicits transient
spells of dystonia and choreiform dyskinesia in patients
with paroxysmal non-kinesigenic dyskinesia (DYT8)9.
These genetic–environmental interactions provide
links between the primary and secondary dystonias and
indicate risk factors for individuals with a hereditary
susceptibility, including intrinsic or extrinsically driven
Several of the hereditary primary dystonias impli-
cate altered synaptic communication within the basal
ganglia. For example, torsina, which is encoded by the
DYT1 gene (also known as TOR1A), is expressed at
high levels in human dopaminergic neurons10. DYT1
dystonia does not respond to the dopamine precur-
sor L-dihydroxyphenylalanine (L-dopa), but it does
improve with high doses of anticholinergic drugs. a
link between abnormal responses to dopaminergic sig-
nalling and increased acetylcholine release has recently
been reported in a mouse model of DYT1 dystonia11.
Dopa-responsive dystonia (DRD, also known as DYT5)
improves dramatically with administration of L-dopa
and also responds to anticholinergic agents. Other
hereditary dystonias, such as DYT3 and DYT12, include
parkinsonian features such as bradykinesia. DYT3 is
associated with neurodegeneration of striatal neurons
that receive dopaminergic input12 and can be considered
a form of parkinsonism. In addition, patients with juvenile
Parkinson’s disease often present with dystonic symptoms,
and patients with typical adult-onset idiopathic Parkinson’s
disease can have dramatic dystonic manifestations when
coming on or off L-dopa therapy13. These findings suggest
that the level of dopamine in the striatum, either too little
or too much, can cause dystonia.
Early-onset, torsion dystonia. Early-onset, torsion dys-
tonia (DYT1) is a severe form of hereditary, generalized
dystonia14. Onset of dystonia in DYT1 usually occurs
between 5 to 28 years of age, a distinct developmental
window of susceptibility that overlaps with a period of
high motor learning. In very early-onset cases, symptoms
typically begin in a lower limb and progress up the body
over the following years. In contrast, later-onset cases
are usually limited to upper-body parts, correlating with
a somatotopic gradient in the basal ganglia. although
Table 1 | Monogenic forms of primary dystonia*
Early-onset generalized torsion dystonia
(dystonia musculorum deformans,
Autosomal recessive torsion dystonia
Mode of inheritance
Disease-specific changes in
Myofibrillogenesis regulator 1
‘Non-DYT1’ dystonia (whispering dysphonia)
Dopa-responsive dystonia (DRD)
Autosomal dominant (Segawa)
Autosomal recessive (DRD)
Adolescent-onset dystonia of mixed type
Adult-onset focal dystonia
Paroxysmal non-kinesigenic dyskinesia
Paroxysmal choreoathetosis with episodic
ataxia and spasticity
Paroxysmal kinesigenic choreoathetosis
DYT12 Rapid-onset dystonia-parkinsonism 19q
Na+/K+ ATPase α3 subunit
* Modified, with permission, from ref. 4 (2007) Taylor & Francis Group.
naTuRE REvIEWS | neuroscience
vOLuME 9 | MaRcH 2008 | 223
© 2008 Nature Publishing Group
38. Ichinose, H. et al. Hereditary progressive dystonia with
marked diurnal fluctuation caused by mutations in the
GTP cyclohydrolase I gene. Nature Genet. 8, 236–242
This landmark paper identified the defect in dopa-
responsive dystonia and revealed the central role
of altered dopamine biosynthesis in this syndrome.
39. Maita, N., Hatakeyama, K., Okada, K. &
Hakoshima, T. Structural basis of biopterin-induced
inhibition of GTP cyclohydrolase I by GFRP, its
feedback regulatory protein. J. Biol. Chem. 279,
40. Levine, R. A., Miller, L. P. & Lovenberg, W.
Tetrahydrobiopterin in striatum: localization in
dopamine nerve terminals and role in catecholamine
synthesis. Science 214, 919–921 (1981).
41. Ludecke, B., Dworniczak, B. & Bartholome, K. A point
mutation in the tyrosine hydroxylase gene associated
with Segawa’s syndrome. Hum. Genet. 95, 123–125
42. Knappskog, P. M., Flatmark, T., Mallet, J., Ludecke, B.
& Bartholome, K. Recessively inherited
L-DOPA-responsive dystonia caused by a point
mutation (Q381K) in the tyrosine hydroxylase gene.
Hum. Mol. Genet. 4, 1209–1212 (1995).
43. Swaans, R. J. et al. Four novel mutations in the
tyrosine hydroxylase gene in patients with infantile
parkinsonism. Ann. Hum. Genet. 64, 25–31 (2000).
44. Royo, M., Daubner, S. C. & Fitzpatrick, P. F. Effects of
mutations in tyrosine hydroxylase associated with
progressive dystonia on the activity and stability of the
protein. Proteins 58, 14–21 (2005).
45. Friedman, J. & Standaert, D. G. Neurogenetics of
dystonia and paroxysmal dyskinesias, in Neurogenetics:
Clinical and Scientific Advances (ed. Lynch, D. R.)
403–426 (Marcel Dekker, Inc., New York, 2005).
46. Rainier, S. et al. Myofibrillogenesis regulator 1 gene
mutations cause paroxysmal dystonic choreoathetosis.
Arch. Neurol. 61, 1025–1029 (2004).
47. Saunders-Pullman, R., Ozelius, L. & Bressman, S. B.
Inherited myoclonus-dystonia. Adv. Neurol. 89,
48. Saunders-Pullman, R. et al. Myoclonus dystonia:
possible association with obsessive-compulsive
disorder and alcohol dependence. Neurology 58,
49. Asmus, F. et al. Myoclonus-dystonia due to genomic
deletions in the epsilon-sarcoglycan gene. Ann. Neurol.
58, 792–797 (2005).
50. Piras, G. et al. Zac1 (Lot1), a potential tumor
suppressor gene, and the gene for epsilon-sarcoglycan
are maternally imprinted genes: identification by a
subtractive screen of novel uniparental fibroblast lines.
Mol. Cell Biol. 20, 3308–3315 (2000).
51. Yokoi, F., Dang, M. T., Mitsui, S. & Li, Y. Exclusive
paternal expression and novel alternatively spliced
variants of epsilon-sarcoglycan mRNA in mouse brain.
FEBS Lett. 579, 4822–4828 (2005).
52. Muller, B. et al. Evidence that paternal expression of
the epsilon-sarcoglycan gene accounts for reduced
penetrance in myoclonus-dystonia. Am. J. Hum. Genet.
71, 1303–1311 (2002).
53. Zimprich, A. et al. Mutations in the gene encoding
epsilon-sarcoglycan cause myoclonus-dystonia
syndrome. Nature Genet. 29, 66–69 (2001).
This study identified the gene responsible for
DYT11 dystonia with supporting evidence for
maternal inheritance and a potential insight into
dystrophin–glycoprotein complexes in the brain.
54. Esapa, C. T. et al. SGCE missense mutations that
cause myoclonus-dystonia syndrome impair epsilon-
sarcoglycan trafficking to the plasma membrane:
modulation by ubiquitination and torsinA. Hum. Mol.
Genet. 16, 327–342 (2007).
55. Xiao, J. & LeDoux, M. S. Cloning, developmental
regulation and neural localization of rat epsilon-
sarcoglycan. Brain Res. Mol. Brain Res. 119,
56. Chan, P. et al. Epsilon-sarcoglycan immunoreactivity
and mRNA expression in mouse brain. J. Comp.
Neurol. 482, 50–73 (2005).
57. Leung, J. C. et al. Novel mutation in the TOR1A
(DYT1) gene in atypical early onset dystonia and
polymorphisms in dystonia and early onset
parkinsonism. Neurogenetics 3, 133–143 (2001).
58. Klein, C. et al. Epsilon-sarcoglycan mutations found in
combination with other dystonia gene mutations. Ann.
Neurol. 52, 675–679 (2002).
59. Brashear, A. et al. The phenotypic spectrum of rapid-
onset dystonia-parkinsonism (RDP) and mutations in
the ATP1A3 gene. Brain 130, 828–835 (2007).
60. de Carvalho Aguiar, P. et al. Mutations in the Na+/K+ -
ATPase alpha3 gene ATP1A3 are associated with
rapid-onset dystonia parkinsonism. Neuron 43,
61. Rodacker, V., Toustrup-Jensen, M. & Vilsen, B.
Mutations Phe785Leu and Thr618Met in Na+, K+-
ATPase, associated with familial rapid-onset dystonia
parkinsonism, interfere with Na+ interaction by
distinct mechanisms. J. Biol. Chem. 281,
62. Cannon, S. C. Pathomechanisms in channelopathies of
skeletal muscle and brain. Annu. Rev. Neurosci. 29,
63. Evinger, C. Animal models of focal dystonia. NeuroRx
2, 513–524 (2005).
64. Jinnah, H. A. et al. Animal models for drug discovery
in dystonia. Expert Opin. Drug Disc. 3, 83–97 (2008).
65. Koh, Y. H., Rehfeld, K. & Ganetzky, B. A Drosophila
model of early onset torsion dystonia suggests
impairment in TGF-beta signaling. Hum. Mol. Genet.
13, 2019–2030 (2004).
66. Muraro, N. I. & Moffat, K. G. Down-regulation
of torp4a, encoding the Drosophila homologue of
torsinA, results in increased neuronal degeneration.
J. Neurobiol. 66, 1338–1353 (2006).
67. Byl, N. N. Learning-based animal models: task-specific
focal hand dystonia. ILAR J 48, 411–431 (2007).
Summarizes an elegant series of experiments
linking changes in sensory maps in the brain
to the pathogenesis of focal dystonia, emphasizing
the role of sensorimotor plasticity in dystonia.
68. Sharma, N. et al. Impaired motor learning in mice
expressing torsinA with the DYT1 dystonia mutation.
J. Neurosci. 25, 5351–5355 (2005).
69. Shashidharan, P. et al. Transgenic mouse model of
early-onset DYT1 dystonia. Hum. Mol. Genet. 14,
70. Grundmann, K. et al. Overexpression of human
wildtype torsinA and human DeltaGAG torsinA in a
transgenic mouse model causes phenotypic
abnormalities. Neurobiol. Dis. 27, 190–206 (2007).
71. Dang, M. T. et al. Generation and characterization of
Dyt1 DeltaGAG knock-in mouse as a model for early-
onset dystonia. Exp. Neurol. 196, 452–463 (2005).
Together with references 26 and 76, this paper
establishes that the DYT1-associated GAG deletion
renders torsinA nonfunctional in the setting of a
homozygous knock-in mouse.
72. Balcioglu, A. et al. Dopamine release is impaired in a
mouse model of DYT1 dystonia. J. Neurochem. 102,
73. Pisani, A. et al. Altered responses to dopaminergic D2
receptor activation and N-type calcium currents in
striatal cholinergic interneurons in a mouse model of
DYT1 dystonia. Neurobiol. Dis. 24, 318–325 (2006).
74. Ghilardi, M. F. et al. Impaired sequence learning in
carriers of the DYT1 dystonia mutation. Ann. Neurol.
54, 102–109 (2003).
75. Yokoi, F., Dang, M. T., Mitsui, S., Li, J. & Li, Y. Motor
deficits and hyperactivity in cerebral cortex-specific
Dyt1 conditional knockout mice. J. Biochem. 143,
76. Dang, M. T., Yokoi, F., Pence, M. A. & Li, Y. Motor
deficits and hyperactivity in Dyt1 knockdown mice.
Neurosci. Res. 56, 470–474 (2006).
77. Hyland, K., Gunasekara, R. S., Munk-Martin, T. L.,
Arnold, L. A. & Engle, T. The hph-1 mouse: a model for
dominantly inherited GTP-cyclohydrolase deficiency.
Ann. Neurol. 6, S46–48 (2003).
78. Yokoi, F., Dang, M. T., Li, J. & Li, Y. Myoclonus, motor
deficits, alterations in emotional responses and
monoamine metabolism in epsilon-sarcoglycan deficient
mice. J. Biochem. (Tokyo) 140, 141–146 (2006).
This mouse model of DYT11 dystonia most
accurately reflects symptoms seen in patients with
myoclonus dystonia, as compared to other rodent
models of dystonia.
79. Moseley, A. E. et al. Deficiency in Na, K-ATPase alpha
isoform genes alters spatial learning, motor activity,
and anxiety in mice. J. Neurosci. 27, 616–26 (2007).
80. Brown, A., Bernier, G., Mathieu, M., Rossant, J. &
Kothary, R. The mouse dystonia musculorum gene is a
neural isoform of bullous pemphigoid antigen 1.
Nature Genet. 10, 301–306 (1995).
81. Liu, J. J. et al. Retrolinkin, a membrane protein, plays
an important role in retrograde axonal transport.
Proc. Natl Acad. Sci. USA 104, 2223–2228 (2007).
82. Young, K. G., Pinheiro, B. & Kothary, R. A Bpag1
isoform involved in cytoskeletal organization
surrounding the nucleus. Exp. Cell Res. 312, 121–134
83. Berardelli, A. et al. The pathophysiology of primary
dystonia. Brain 121, 1195–1212 (1998).
84. Richter, A. The genetically dystonic hamster: an animal
model of paroxysmal dystonia, in Animal Models of
Movement Disorders (ed. LeDoux, M.) 459–466
(Elsevier Academic Press, San Diego, 2005).
85. Sander, S. E. & Richter, A. Effects of intrastriatal
infections of glutamate receptor antagonists on the
severity of paroxysmal dystonia in the dtsz mutant.
Eur. J. Pharmacol. 563, 102–108 (2007).
86. LeDoux, M. Animal Models Movement Disorders,
241–252 (Elsevier Academic Press, Burlington,
87. Xiao, J., Gong, S. & LeDoux, M. S. Caytaxin deficiency
disrupts signaling pathways in cerebellar cortex.
Neuroscience 144, 439–461 (2007).
88. Buschdorf, J. P. et al. Brain-specific BNIP-2-homology
protein Caytaxin relocalises glutaminase to neurite
terminals and reduces glutamate levels. J. Cell Sci.
119, 3337–3350 (2006).
89. Defazio, G., Berardelli, A. & Hallett, M. Do primary
adult-onset focal dystonias share aetiological factors?
Brain 130, 1183–1193 (2007).
90. Chase, T. N., Tamminga, C. A. & Burrows, H. Positron
emission tomographic studies of regional cerebral
glucose metabolism in idiopathic dystonia. Adv.
Neurol. 50, 237–241 (1988).
91. Perlmutter, J. S. et al. Decreased [18F]spiperone
binding in putamen in idiopathic focal dystonia.
J. Neurosci. 17, 843–850 (1997).
This study provided the first direct neural (as
opposed to clinical) evidence that dopaminergic
abnormalities might be involved in some human
forms of dystonia.
92. Asanuma, K. et al. Decreased striatal D2 receptor
binding in non-manifesting carriers of the DYT1
dystonia mutation. Neurology 64, 347–349 (2005).
93. Rinne, J. O. et al. Striatal dopaminergic system in
dopa-response dystonia: a multi-tracer PET study
shows increased D2 receptors. J. Neural. Transm. 111,
94. Eidelberg, D. et al. Functional brain networks in DYT1
dystonia. Ann. Neurol. 44, 303–312 (1998).
This fMRI study established dystonia as a network
disorder and set the design and interpretation of
future functional imaging studies, highlighting that
dystonia patients, even at rest, do not have the
same functional neural baseline as healthy
controls. It provided a means to distinguish the
brain regions involved in dystonic symptoms
themselves (movement-related regions) from those
which may underlie more fundamental
endophenotypic traits of the disorder (movement-
95. Ceballos-Baumann, A. O. et al. Overactive prefrontal
and underactive motor cortical areas in idiopathic
dystonia. Ann. Neurol. 37, 363–372 (1995).
96. Ibanez, V., Sadato, N., Karp, B., Deiber, M. P. &
Hallett, M. Deficient activation of the motor cortical
network in patients with writer’s cramp. Neurology
53, 96–105 (1999).
97. Dresel, C., Haslinger, B., Castrop, F., Wohlschlaeger,
A. M. & Ceballos-Baumann, A. O. Silent event-related
fMRI reveals deficient motor and enhanced
somatosensory activation in orofacial dystonia. Brain
129, 36–46 (2006).
98. Blood, A. J. et al. Basal ganglia activity remains
elevated after movement in focal hand dystonia.
Ann. Neurol. 55, 744–748 (2004).
99. Pujol, J. et al. Brain cortical activation during guitar-
induced hand dystonia studied by functional MRI.
Neuroimage 12, 257–267 (2000).
100. Ikoma, K., Samii, A., Mercuri, B., Wassermann, E. M.
& Hallett, M. Abnormal cortical motor excitability in
dystonia. Neurology 46, 1371–1376 (1996).
This study was key to establishing the idea that
abnormal excitability of motor-system neural
function could be a physiological mechanism
101. DeLong, M. R. Primate models of movement disorders
of basal ganglia origin. Trends Neurosci. 13, 281–285
102. Carbon, M. et al. Microstructural white matter
changes in carriers of the DYT1 gene mutation. Ann.
Neurol. 56, 283–286 (2004).
103. Colosimo, C. et al. Diffusion tensor imaging in primary
cervical dystonia. J. Neurol. Neurosurg. Psychiatry
76, 1591–1593 (2005).
104. Blood, A. J. et al. White matter abnormalities in
dystonia normalize after botulinum toxin treatment.
Neuroreport 17, 1251–1255 (2006).
naTuRE REvIEWS | neuroscience
vOLuME 9 | MaRcH 2008 | 233
© 2008 Nature Publishing Group
105. Draganski, B., Thun-Hohenstein, C., Bogdahn, U.,
Winkler, J. & May, A. “Motor circuit” gray matter
changes in idiopathic cervical dystonia. Neurology 61,
106. Garraux, G. et al. Changes in brain anatomy in focal
hand dystonia. Ann. Neurol. 55, 736–739 (2004).
107. Delmaire, C. et al. Structural abnormalities in the
cerebellum and sensorimotor circuit in writer’s cramp.
Neurology 69, 376–380 (2007).
108. Etgen, T., Muhlau, M., Gaser, C. & Sander, D. Bilateral
grey-matter increase in the putamen in primary
blepharospasm. J. Neurol. Neurosurg. Psychiatry 77,
109. Egger, K. et al. Voxel based morphometry reveals
specific gray matter changes in primary dystonia. Mov.
Disord. 22, 1538–1542 (2007).
110. Hallett, M. Pathophysiology of dystonia. J. Neural.
Transm. 70, S485–S488 (2006).
111. Quartarone, A., Siebner, H. R. & Rothwell, J. C.
Task-specific hand dystonia: can too much plasticity be
bad for you? Trends Neurosci. 29, 192–199 (2006).
This article summarises recent results concerning
abnormalities of plasticity in dystonia and explains
how abnormal plasticity can give rise to dystonia.
Although the discussion is most appropriate to
focal hand dystonia, the ideas are generalizable to
other forms of dystonia.
112. Weise, D. et al. The two sides of associative plasticity
in writer’s cramp. Brain 129, 2709–2721 (2006).
113. Bara-Jimenez, W., Catalan, M. J., Hallett, M. &
Gerloff, C. Abnormal somatosensory homunculus in
dystonia of the hand. Ann. Neurol. 44, 828–831
114. Byl, N. N., McKenzie, A. & Nagarajan, S. S.
Differences in somatosensory hand organization in a
healthy flutist and a flutist with focal hand dystonia:
a case report. J. Hand Ther. 13, 302–309 (2000).
115. Meunier, S. et al. Human brain mapping in dystonia
reveals both endophenotypic traits and adaptive
reorganization. Ann. Neurol. 50, 521–527 (2001).
116. Thickbroom, G. W., Byrnes, M. L., Stell, R. &
Mastaglia, F. L. Reversible reorganisation of the motor
cortical representation of the hand in cervical
dystonia. Mov. Disord. 18, 395–402 (2003).
117. Fiorio, M., Tinazzi, M. & Aglioti, S. M. Selective
impairment of hand mental rotation in patients with
focal hand dystonia. Brain 129, 47–54 (2006).
118. Sanger, T. D., Tarsy, D. & Pascual-Leone, A.
Abnormalities of spatial and temporal sensory
discrimination in writer’s cramp. Mov. Disord. 16,
119. Rosenkranz, K., Altenmuller, E., Siggelkow, S. &
Dengler, R. Alteration of sensorimotor integration in
musician’s cramp: impaired focusing of proprioception.
Clin. Neurophysiol. 111, 2040–2045 (2000).
120. Hallett, M. Dystonia: abnormal movements result
from loss of inhibition. Adv. Neurol. 94, 1–9 (2004).
121. Espay, A. J. et al. Cortical and spinal abnormalities in
psychogenic dystonia. Ann. Neurol. 59, 825–834 (2006).
122. Jankovic, J. Treatment of dystonia. Lancet Neurol. 5,
123. Curra, A., Trompetto, C., Abbruzzese, G. & Berardelli, A.
Central effects of botulinum toxin type A: evidence
and supposition. Mov. Disorder. 19, S60–64 (2004).
124. Tagliati, M., Shils, J., Sun, C. & Alterman, R. Deep
brain stimulation for dystonia. Expert Rev. Med.
Devices 1, 33–41 (2004).
125. Vidailhet, M. et al. Bilateral, pallidal, deep-brain
stimulation in primary generalised dystonia: a
prospective 3 year follow-up study. Lancet Neurol. 6,
126. Alterman, R. L. & Snyder, B. J. Deep brain stimulation
for torsion dystonia. Acta Neurochir Suppl, 97,
127. Zhang, J. G., Zhang, K., Wang, Z. C., Ge, M. & Ma, Y.
Deep brain stimulation in the treatment of secondary
dystonia. Chin. Med. J. (Eng) 119, 2069–2074
128. Arnon, S. S. et al. Botulinum toxin as a biological
weapon. JAMA 285, 1059–1070 (2001).
129. Sharma, N. & Richman, E. Parkinson’s Disease and
the Family, A New Guide, (Harvard University Press
Family Health Guides, USA, 2005).
We thank S. McDavitt for skilled editorial assistance.
Funding was provided by the Bachmann-Strauss Dystonia
and Parkinson Foundation (X.O.B., Y.L. and D.G.S.), the
Jack Fasciana Fund for Support of Dystonia Research
(X.O.B.), the Dystonia Medical Research Foundation
(A.B. and Y.L.), National Institute of Neurological Disorders
and Stroke (NINDS) NS37409 (X.O.B. and D.G.S.),
NS047692 (Y.L.), NS050717 (P.I.H.) and NINDS intramural
Entrez Gene: http://www.ncbi.nlm.nih.gov/entrez/query.
ATP1A3 | PNKD | TOR1A
DYT1 | DYT3 | DYT5 | DYT8 | DYT12
Bpag1 | ε-sarcoglycan | LAP1 | TAF1 | TH | torsinA
Xandra Breakefield’s homepage:
All links Are AcTiVe in THe online PDF
234 | MaRcH 2008 | vOLuME 9
© 2008 Nature Publishing Group