Movement Disorders
Vol. 25, No. 5, 2010, pp. 647–658
Ó 2010 Movement Disorder Society
Letters to the Editor Related to New Topics
Agrypnia with Nocturnal Confusional
Behaviors in Dementia with Lewy Bodies:
Immediate Efficacy of Rivastigmine
Video
A confusional, delirious state occurring at twilight and into
the evening/night has been reported in patients with demen-
tia.1 This disturbance has been linked to arousal disorders
with cortical deactivation.2
We describe a woman aged 76 years affected by severe
insomnia with aberrant nocturnal behaviors, whose appear-
ance preceded the clinical evolution that allowed a diagnosis
of probable dementia with Lewy bodies (LBD). Nocturnal
agitation, wandering, and falls out of bed were reported.
Structured visual hallucinations (her husband, unknown peo-
ple or dead relatives) were described. A neuropsychological
evaluation 18 months before our observation revealed only
mild reduction in short-term verbal memory. At our observa-
tion, a mild hypokinetic-rigid parkinsonism with right-side
prevalence of motor symptoms (UPDRS part III: 21) was
present, mildly improved (UPDRS part III: 12) after one
week of levodopa therapy (300 mg/day).
Diurnal fluctuations of cognition with confusional spells
and excessive sleepiness were present; neuropsychological
evaluations (24-hour test–retest interval) documented day-to-
day fluctuations, MMSE score of 20.7 in more alert state and
deficits (equivalent scores,3 calculated from the raw scores,
considered pathological when equal to or less than one) in
logic-executive (Weigl’s Sorting Test, Raven’s colored matri-
ces 47, frontal assessment battery, phonemic and semantic
verbal fluency) and visuo-constructional abilities (Rey-Oster-
rieth complex figure immediate and delayed copying).
Brain MRI revealed diffuse cortical atrophy, SPECT imag-
ing showed decreased presynaptic dopamine reuptake in the
putamen and in the caudate nucleus.
Video-polysomnography (video-PSG) demonstrated severe
disorganization of sleep with subcontinuous wakefulness
interrupted by short periods of NREM sleep (Fig. 1) and,
during wakefulness, recurrent anomalous movements of the
whole body or parts of the body, including rhythmic scratch-
ing of the head, nose, pelvic region, and legs; at times the
patient attempted to climb over the bars applied to the bed or
got on her hands and knees (Video 1).
These manifestations occurred unchanged every night until
rivastigmine 3 mg was administered: video-PSG documented
Additional Supporting Information may be found in the online
version of this article.
Potential conflict of interest: Nothing to report.
Published online 19 February 2010 in Wiley InterScience
(www. interscience.wiley.com). DOI: 10.1002/mds.22726
647
considerable restoration of sleep, without confusional mani-
festations, in the presence of REM sleep without atonia.
Three months after discharge, follow-up video-PSG con-
firmed partial restoration of sleep structure without abnormal
behaviors.
Fifteen months after a fourth follow-up video-PSG con-
firmed the organization of nocturnal sleep into NREM/REM
periods, although insomnia persisted. A short confusional
arousal (Fig. 1, black arrow) was documented.
The first night of rivastigmine discontinuation, a fifth
video-PSG documented the reappearance of complete insom-
nia with confusional behaviors: the patient repeatedly got out
and even fell out of bed, fiddled with her clothing, and the
recording device detaching the leads.
Rivastigmine 3 mg twice a day was reintroduced leading
to sudden remission of night-time symptoms, confirmed at a
clinical follow up 12 months later.
The night-time sleeplessness observed in this patient with
incessant movements and wandering had begun before a pic-
ture of dementia appeared, and were reminiscent of sundown-
ing.4 Sundowning consists of sleep-wake pattern disruption
and behavioral abnormalities, peaking in the early evening and
continuing into the night. There are no reports of severe insom-
nia with confusional behaviors as heralding symptoms of LBD.
In familial alpha-synucleinopathy, insomnia and sleep-related
behavioral abnormalities (vocalizations, aggressive move-
ments, falls) were reported, based on patient histories, to ante-
date the parkinsonian syndrome, but as independent features.5
Nocturnal paroxysmal episodes in the form of REM sleep
behavior disorder (RBD) have been shown to harbinger synu-
cleinopathies6 and are so frequent in LBD that it has been
included in the diagnostic criteria as a feature suggestive of a
diagnosis.7 However, RBD is by definition an abnormal behav-
ior emerging during REM sleep, whereas in the described sub-
ject the confusional behaviors occurred during a state that was
not scorable as REM sleep. Although sleep stage differentiation
can be challenging in extrapyramidal disorders, trained scorers
can reliably distinguish REM sleep from wakefulness and
NREM sleep: all the motor-behavioral manifestations recorded
in the described subject occurred during clearly identifiable
wakefulness.8
RBD can be deemed a simpler manifestation of status dis-
sociatus, which is a clinical and polygraphic condition in
which the various states of being (i.e., wakefulness, NREM
and REM sleep) are simultaneously present. In this case, col-
lapse of state determinants results in the inability to identify
conventional stages during sleep. However, we cannot exclude
with certainty the existence of covert REM sleep during other
states of being,9 namely during wakefulness, which might be
responsible for the behavioral abnormalities observed.
On the other hand, in a similar way, it has been proposed
that sundowning is related to a state of conflict between ele-
ments of wakefulness and NREM sleep; in this state, the cor-
tex, having prepared for sleep, is unable to process correctly
648 LETTERS TO THE EDITOR

FIG. 1. Sleep hypnograms during observation. (A) Baseline: subcontinuous wakefulness intermingled with very short periods of NREM sleep.
(B) First night with rivastigmine: reappearance of REM sleep in clearly recognizable NREM-REM sleep cycles. (C) Three months and (D) 15
months follow up with rivastigmine: persisting recovery, despite abundant wake activity. (E) Rivastigmine withdrawal: continuous wakefulness,
complete agrypnia. (1) Confusional arousal like episode and (2) electrode detachment during confusional manifestations.

the continuous stream of information deriving from the wake cycle, and preventing confusional episodes during night-
patient’s wakeful state.2 The suggestion is that the inability time wakefulness (one very brief confusional arousal-like epi-
to sustain arousal during behavioral wakefulness, with sode occurred, but it did not affect the overall sleep pattern).
NREM sleep intruding into it, creates the substrate for confu-
sion. Such a breakdown of the boundaries between wakeful-
ness and NREM sleep, resulting in the coexistence of con- LEGENDS TO THE VIDEO
flicting elements of different local states of being, has been
documented.10 Indeed, it can be hypothesized that sleep onset Video-PSG on admission. This video shows global slow
mechanisms (involving a complex interrelationship between movement, by which the patients get on her hands and knees
multiple neurotransmitters11) could be altered, resulting in a assuming and keeping a position which reminds that of a
state of persisting behavioral wakefulness, and, at the same ‘‘Muslim in praying.’’
time, that this wakefulness is, vice versa, weakened by the
state of reduced arousal. Michele Terzaghi*
In our case, administration of rivastigmine quickly recov- Valter Rustioni
ered sleep patterns and the behavioral disturbances, display- Raffaele Manni
ing a rapid switch on/switch off effect. Loci of degeneration Sleep Medicine and Epilepsy Unit
in LBD-related neuropathology are found in several nuclei IRCCS ‘‘C. Mondino Institute of Neurology’’ Foundation
(including the cholinergic nuclei) involved in sleep regula- Pavia, Italy
tion.7 Release of acetylcholine (Ach) has, for years, known *E-mail: michele.terzaghi@mondino.it
to be essential for vigilance and cortical activation during
wakefulness, controlling cortical arousal and awareness,
while its reduction supports the slow-wave component of Claudio Pacchetti
NREM sleep. Furthermore, Ach is thought to be involved in Roberta Zangaglia
the circuitry mediating REM sleep: in our patient REM sleep Maria Ossola
was present only during rivastigmine therapy, and was unde- Parkinson’s Disease and Movement Disorders Unit
tectable in the absence of the drug. IRCCS "C. Mondino Institute of Neurology’’ Foundation
Restoring Ach activity in our patient proved to be a suc- University of Pavia
cessful therapeutic strategy, partially re-establishing sleep/ Pavia, Italy

Movement Disorders, Vol. 25, No. 5, 2010

 LETTERS TO THE EDITOR
References
1. Bliwise DL. What is sundowning? J Am Geriatr Soc 1994;42:
1009–1011.
2. Staedt J, Stoppe G. Treatment of rest-activity disorders in de-
mentia and special focus on sundowning. Int J Geriatr Psychiatry
2005;20:507–511.
3. Capitani E, Laiacona M. Composite neuropsychological batteries
and demographic correction: standardization based on equivalent
scores, with a review of published data. The Italian Group for
the Neuropsychological Study of Ageing. J Clin Exp Neuropsy-
col 1997;19:795–809.
4. Nowak L, Davis JE. A qualitative examination of the phenom-
enon of sundowning. J Nurs Scholarsh 2007;39:256–258.
5. Zarranz JJ, Fernàndez-Bedoya A, Lambarri I, et al. Abnormal
sleep architecture is an early feature in the E46K familial synu-
cleinopathy. Mov Disord 2005;20:1310–1315.
6. Boeve BF, Silber MH, Ferman TJ, et al. REM sleep
behavior disorder and degenerative dementia: an association
likely reflecting Lewy body disease. Neurology 1998;51:363–
370.
7. McKeith IG, Dickson DW, Lowe J, et al. Consortium on DLB.
Diagnosis and management of dementia with Lewy bodies: third
report of the DLB Consortium. Neurology 2005;65:1863–1872.
8. Bliwise DL, Willians ML, Irbe D, Ansari FP, Rye DB. Inter-rater
reliability for identification of REM sleep in Parkinson’s disease.
Sleep 2000;23:671–676.
9. Nielsen TA. A review of mentation in REM and NREM sleep:
‘‘covert’’ REM sleep as a possible reconciliation of two opposing
models. Behav Brain Sci 2000;23:851–866.
10. Terzaghi M, Sartori I, Tassi L, et al. Evidence of dissociated
arousal states during NREM parasomnia from an intracerebral
neurophysiological study. Sleep 2009;32:409–412.
11. Jones BE. Basic mechanisms of sleep-wake states. In: Kryger
MH, Roth T, Dement WC, editors. Principles and practice of
sleep medicine, Third ed. Philadelphia, USA: W.B. Saunders
Company; 2000. p 134–154.
Hyperintensity in the Basis Pontis: Atypical
Neuroradiological Findings in a Woman
with FXTAS
A CGG trinucleotide repeat expansion in the fragile X men-
tal retardation 1 gene (FMR1) within the premutation range
(55–200 CGG repeats) is associated with the fragile X-asso-
ciated tremor/ataxia syndrome (FXTAS), a late-onset neuro-
degenerative disorder. An explanation for neurodegenerative
changes assumes that the expanded-repeats in the RNA tran-
script exerts a toxic gain-of-function effect on cellular metab-
olism by interfering with the binding of several RNA proc-
essing factors, leading to functional changes in the
corresponding proteins.1
FXTAS is characterized by a progressive action tremor
and cerebellar ataxia; parkinsonism, polyneuropathy, dysauto-
nomia, and cognitive decline may be variable associated.1
MR imaging contributes to identification of FXTAS and the
typical findings are brain atrophy, subcortical, and periven-
Potential conflict of interest: Nothing to report.
Published online 3 March 2010 in Wiley InterScience (www.
interscience.wiley.com). DOI: 10.1002/mds.22811
649
tricular white matter disease, including increased signal inten-
sity in T-2 weighted images of the middle cerebellar
peduncle (MCP).2 The clinical and radiological spectrum in
affected women is not well defined because of the low pene-
trance in females.3 Here, we report a female premutation car-
rier with atypical neuroradiological findings.
A 70-year-old woman developed postural and action
tremor of both hands 5 years before. Her past medical history
included depression and subclinical hypothyroidism. She had
no premature ovarian failure, arterial hypertension, peripheral
neuropathy, seizures, or fibromyalgia. She had one daughter
and two sons. Her two daughter’s sons had been diagnosed
of fragile X syndrome.
A diagnosis of Parkinson’s disease was made 2 years
before; she was on levodopa (150 mg/d), pramipexole (2.1
mg/d), and rasagiline (1 mg/d) therapy, without any clinical
response. Neurological examination revealed hypomimia and
bilateral mild postural tremor of the upper extremities. Nei-
ther rigidity nor bradykinesia were noted. Mild appendicular
ataxia was present in upper and lower extremities. There was
no sign of pyramidal, eye movement, or autonomic system
involvement. No cognitive impairment was detected by the
Folstein Mini-Mental Status Examination test. DNA analysis
demonstrated expansion of 85 CGG repeats in one FMR1 al-
lele, the second allele was normal. The patient’s symptoms
improved after withdrawing dopaminergic therapy. Magnetic
resonance imaging findings in this case were mild cerebral
and cerebellar atrophy, patchy areas of increased signal inten-
sity on T2 weighted or FLAIR images in periventricular and
deep white matter of the cerebral hemispheres and corpus
callosum. There was no increased T2 signal intensity in
white matter of the MCP or in underlying cerebellar white
matter but a striking high signal was seen in the base of the
pons on T2 weighted or FLAIR images (Fig. 1). None of the
lesions showed focal restricted diffusion by using MR
diffusion-weighted imaging (DWI).
Factors that may influence FXTAS involvement in females
are the normal expression of FMR1 from normal allele and
the modification of the effect of CGG repeats induced by the
activation ratio.1 The neurological symptoms are usually
much milder in females than males. In like manner, milder
FIG. 1. Axial FLAIR images depict intense hyperintensities in basis
pontis with normal findings in middle cerebellar peduncles. The pon-
tine tegmentum and the superior cerebellar peduncles are also
involved (arrows).
Movement Disorders, Vol. 25, No. 5, 2010
650 LETTERS TO THE EDITOR
radiological findings in females affected by FXTAS when
compared with males were reported. Adams et al. docu-
mented lower incidence of the MCP signs and less pro-
nounced cerebellar volume loss.4
From neurons in the basis pontis arises the major afferent
pathway into the cerebellum; these axons form the transverse
pontine fibres and the MCPs. The neuropathological study of
brains of patients with FXTAS demonstrated the presence of
white matter disease within the cerebrum and cerebellum in
relationship with spongiosis with rare axonal spheroids and
myelin pallor. Abnormal MCPs white matter disease was
present but abnormal pons white matter was not mentioned.5
In patients with FXTAS, abnormal high intensity was seen in
MCP but in only few cases it was accompanied by a signal
intensity changes in T-2 weighted images of the pons.6–8 In our
patient, the transverse pontine fibers, but not MCP, are prob-
ably degenerated, reflecting these changes is the abnormal
high-signal observed in the basis pontis The MR findings
shown in this study are not specific, a differential diagnosis
with central pontine myelinolysis (CPM) needs to be consid-
ered but DWI demonstrates restricted diffusion within the cen-
tral pons in CPM.9 Thus, this case exemplifies the diversity of
MRI abnormalities that could be associated with this condition
and expands its neuroradiological features beyond the typical
MCP sign. In addition, this case shows the discrepancy between
the MRI findings and the minimal clinical manifestations.
Financial Disclosures: G. Morı́s: none. M. Arias: none.
M.V. López: none. V. Álvarez: none.
Author Roles: G. Morı́s and M. Arias—contributed to the
conception and organization of the manuscript. G. Morı́s—
wrote the first draft. M. Arias—reviewed the first draft. M.V.
López—performed the magnetic resonance imaging analyses.
V. Álvarez—performed the genetic analyses. All authors read
and approved the final manuscript.
Germán Morı́s, MD*
Mónica Arias, MD
Service of Neurology
Hospital San Agustı´n
Avile´s, Asturias, Spain
*E-mail: gmorist@gmail.com
Maria Valle López, MD
Service of Radiology
Hospital San Agustı´n
Avile´s, Asturias, Spain
Victoria Álvarez, PhD
Molecular Genetics
Hospital Universitario Central Asturias (HUCA)
Oviedo, Asturias, Spain
References
1. Berry-Kravis E, Abrams L, Coffey SM, et al. Fragile X-associated
tremor/ataxia syndrome: clinical features, genetics, and testing
guidelines. Mov Disord 2007;22:2018–2030.
2. Brunberg JA, Jacquemont S, Hagerman RJ, et al. Fragile X pre-
mutation carriers: characteristic MR imaging findings of adult
male patients with progressive cerebellar and cognitive dysfunc-
tion. Am J Neuroradiol 2002;23:1757–1766.
Movement Disorders, Vol. 25, No. 5, 2010
3. Coffey SM, Cook K, Tartaglia N, et al. Expanded clinical pheno-
type of women with the FMR1 premutation. Am J Med Genet A
2008;146A:1009–1016.
4. Adams JS, Adams PE, Nguyen D, et al. Volumetric brain changes
in females with fragile X-associated tremor/ataxia syndrome
(FXTAS). Neurology 2007;69:851–859.
5. Greco CM, Berman RF, Martin RM, et al. Neuropathology of
fragile X-associated tremor/ataxia syndrome (FXTAS). Brain
2006;129 (Part 1):243–255.
6. Ginestroni A, Guerrini L, Della Nave R, et al. Morphometry and
1H-MR spectroscopy of the brain stem and cerebellum in three
patients with fragile X-associated tremor/ataxia syndrome. Am J
Neuroradiol 2007;28:486–488.
7. Kamm C, Healy DG, Quinn NP, et al. The fragile X tremor ataxia
syndrome in the differential diagnosis of multiple system atrophy:
data from the EMSA Study Group. Brain 2005;128:1855–1860.
8. Jacquemont S, Orrico A, Galli L, et al. Spastic paraparesis, cere-
bellar ataxia, and intention tremor: a severe variant of FXTAS?
J Med Genet 2005;42:e14.
9. Ruzek KA, Campeau NG, Miller GM. Early diagnosis of central
pontine myelinolysis with diffusion-weighted imaging. Am J
Neuroradiol 2004;25:210–213.
Effects of Chronic Subthalamic Stimulation on
Intractable Akathisia in Parkinson’s Disease
Akathisia is defined as a subjective inner restlessness and
a feeling of the need to move, leading to the inability to
remain still.1 It commonly accompanies Parkinson’s disease
(PD).1,2 Although the mechanism of akathisia in PD is still
unclear, antiparkinson treatments seldom relieve akathisia
satisfactorily.1 The effects of subthalamic nucleus deep brain
stimulation (STN-DBS) on motor fluctuation and dyskinesia
have been demonstrated, but its effects on nonmotor symp-
toms of PD are still controversial.3,4 Here, we present three
PD patients whose disabling medically-intractable akathisia
improved after STN-DBS.
A 53-year-old woman with a 12-year history of PD was
admitted for STN-DBS. She had been responding well to
small dose of levodopa (L-dopa) treatment until 3 years
before admission when she developed motor fluctuation. At
the same time, she experienced inner restlessness of sufficient
severity to disable her daily activities at the start of the
‘‘drug-on’’ period. Because more frequent dosing of L-dopa
with combination of entacapone increased the frequency of
akathisia symptoms, the patient preferred not to change medi-
cation schedule despite of significant motor fluctuation. On
admission, she exhibited a continuous stepping movement to
relieve this feeling of restlessness without accompanying dys-
kinesia. She could suppress these leg movements, but only
for a short period of time. She stated that akathisia was a
more disabling symptom than her other parkinsonian symp-
toms. Administration of various medications, including L-
dopa and beta-blockers, failed to improve her akathisia. After
STN-DBS, the patient no longer experienced inner restless-
Potential conflict of interest: Nothing to report.
Published online 8 March 2010 in Wiley InterScience (www.
interscience.wiley.com). DOI: 10.1002/mds.22905
 LETTERS TO THE EDITOR 651

TABLE 1. Clinical characteristics of the patients and the dopa dosage, the beginning-of-dose akathisia without dyski-
effects of STN-DBS treatment nesia and off-period akathisia, respectively, whereas Case 3
did not show this relationship. None of the patients had diur-
Case 1 Case 2 Case 3 nal variation in their akathitic symptoms. Lack of circardian
Sex/age (yr) F/53 F/64 F/55 rhythm in our patients, in addition to feelings of restlessness,
PD duration (yr) 12 11 9 strongly suggests that the clinical syndrome observed in our
Onset age (yr) 41 53 46 patients was akathisia rather than RLS.
Hoehn & Yahr stage 2 3 2 STN-DBS, in addition to its well-known effects on motor
Pre STN DBS disability symptoms, has been reported to have a beneficial effect on
UPDRS III—off 45 48 33
nonmotor symptoms of PD,3,6 although this is still controver-
UPDRS III—on 8 11 3
UPDRS IV—dyskinesia 1 5 6 sial.4 Witjas et al.3 demonstrated that STN-DBS improved
UPDRS IV—motor fluctuation 3 4 4 many of the nonmotor symptoms of their PD patients, includ-
Daily L-dopa dose (mg) 300 1400 600 ing akathisia/restlessness, particularly if these symptoms were
Post STN DBS disability present during the drug off-period.3 Our observations suggest
UPDRS III—off 18 11 18 that STN-DBS is a viable treatment option for controlling in-
UPDRS III—on 3 3 2 tractable akathisia in PD, regardless of its relation to the tim-
UPDRS IV—dyskinesia 1 5 3 ing of L-dopa. Further studies that include a larger number of
UPDRS IV—motor fluctuation 2 2 2 patients are required to confirm the above conclusion.
Daily L-dopa dose (mg) 300 600 450

Financial Disclosures: Hae-Won Shin: none; Jin Woo

Chang: none; Suk Y. Kang: none; Young H. Sohn: Consul-
ness and showed marked improvements in her motor symp- tancy-GlaxoSmithKline (GSK).
toms (Table 1), even though L-dopa dosage was not changed. Author Roles: H.-W. Shin: Organization and execution of
A 64-year-old woman with an 11-year history of PD was research project, conception and writing of the first draft;
admitted for STN-DBS. The duration of the ‘‘drug-on’’ pe- J.W. Chang: Organization and execution of research project;
riod had gradually shortened starting 4 years before admis- S.Y. Kang: Execution of research project; Y.H. Sohn: Con-
sion. The patient experienced an unpleasant feeling of rest- ception and organization of research project, review and cri-
lessness during the ‘‘drug-off’’ period. She was unable to sit tique of the manuscript.
still, and repeatedly stepped on or shook her legs to over-
come this feeling. She was able to suppress these leg move-
Hae-Won Shin, MD
ments, but only for a short period of time. Her akathisia dis-
appeared when she was in the ‘‘drug-on’’ state after L-dopa Department of Neurology
administration, but other medications, such as propranolol Yonsei University College of Medicine
and benzodiazepine, had no effect. After STN-DBS, her aka- Seoul, Korea
thisia disappeared completely, and she experienced significant Department of Neurology
improvement in motor fluctuation (Table 1). Parkinson/Alzheimer Center, Asan Medical Center
A 55-year-old woman with a 9-year history of PD was University of Ulsan
admitted for STN-DBS. For 3 years before admission, her College of Medicine
‘‘drug-on’’ period had shortened gradually and she began to Seoul, Korea
experience peak-dose dyskinesia. Two years before admis-
sion, she began to experience a feeling of restlessness and a
Jin Woo Chang, MD, PhD
‘‘crawling’’ sensation in her legs. She had to walk continu-
ously to relieve this feeling of restlessness. Her akathisia was Department of Neurosurgery
continuously present while awakening, and was not related to Yonsei University College of Medicine
the timing of medications. Various drugs, including antipar- Seoul, Korea
kinson medications and propranolol, did not relieve her aka-
thisia. After STN-DBS, her akathisia resolved completely, Suk Y. Kang, MD
along with a remarkable improvement in motor fluctuation Department of Neurology
(Table 1). Yonsei University College of Medicine
We have presented three PD patients whose intractable Seoul, Korea
and disabling akathisia disappeared completely after STN- Department of Neurology
DBS, along with a remarkable improvement in parkinsonian Kangnam Sacred Heart Hospital
motor fluctuation. All three patients took postoperative brain
Hallym University College of Medicine
CT scans to confirm that the electrodes were correctly
located in the STN. The clinical syndrome of akathisia over- Seoul, Korea
laps extensively with restless legs syndrome (RLS), which
also commonly accompanies PD.5 Although both disorders Young H. Sohn, MD, PhD*
are accompanied by an urge to move and primarily involve Department of Neurology
the legs, feelings of inner restlessness and lack of circardian Yonsei University College of Medicine
rhythm can be used to differentiate akathisia from RLS.5 Seoul, Korea
Akathisia in Cases 1 and 2 was related to the timing of L- *E-mail: yhsohn62@yuhs.ac

Movement Disorders, Vol. 25, No. 5, 2010

652 LETTERS TO THE EDITOR

References
1. Lang AE, Johnson K. Akathisia in idiopathic Parkinson’s disease.
Neurology 1987;37:477–481.
2. Comella CL, Goetz CG. Akathisia in Parkinson’s disease. Mov
Disord 1994;9:545–549.
3. Witjas T, Kaphan E, Regis J, et al. Effects of chronic subthalamic
stimulation on nonmotor fluctuations in Parkinson’s disease. Mov
Disord 2007;22:1729–1734.
4. Cersosimo MG, Piedimonte F, Raina GB, Micheli FE. Bilateral
STN-DBS fails to improve non-motor fluctuations in a PD patient.
Parkinsonism Relat Disord 2007;13:537–538.
5. Poewe W, Hogl B. Akathisia, restless legs and periodic limb
movements in sleep in Parkinson’s disease. Neurology 2004;63
(8 Suppl 3):S12–S16.
6. Kim HJ, Paek SH, Kim JY, et al. Chronic subthalamic deep brain
stimulation improves pain in Parkinson disease. J Neurol
2008;255:1889–1894.

A New Case of Uner Tan Syndrome—with

Late Childhood Quadrupedalism

Video

In 2005 a novel syndrome characterized by habitual quad-

rupedalism, impaired intelligence, primitive language, and no
conscious experience was first introduced to the scientific
world as Uner Tan syndrome (UTS).1 The patients could all
stand up and walk despite severe ataxia, except one man who
could not rise at all.2 They could walk on all four extremities
with great ease, and all had crawled on hands and knees dur-
ing infantile development, with no hypotonia. The reflexes
were brisk in the lower extremities, and MRI and PET scans
showed inferior cerebello-vermial hypoplasia with a mild
gyral simplification of the cerebral cortex.3 This work
presents a new case having all the symptoms of UTS except
that the quadrupedal locomotion emerged much later in
childhood.
The patient was a 12-year-old boy born by normal deliv-
ery, with no complications during gestation. He was the son
of nonconsanguineous parents with one sister and three
brothers, one of them had no speech. The patient crawled on
hands and knees during infantile development and walked
upright despite truncal ataxia, but two years ago he started to
walk on all four extremities for rapid locomotion. During
quadrupedal locomotion the patient exhibited diagonal-
sequence gait, favored by our early ancestors.4 The attached
video clip shows the patient’s ataxic bipedal walking, sitting,
standing up, and quadrupedal running. This is the first video
report of a case exhibiting Uner Tan syndrome with ‘‘late
childhood quadrupedalism’’. His height, weight, and head cir-
cumference were within normal limits, but his cognitive abil-
ities were severely impaired; he has never spoken. There was
a mild strabismus with no nystagmus; eye movements were
Potential conflict of interest: All authors report no conflict of inter-
est and have no financial disclosure to make.
Published online 19 February 2010 in Wiley InterScience
(www.interscience.wiley.com). DOI: 10.1002/mds.22951
FIG. 1. Brain sagittal (above) and coronal (below) MRI: vermial
and cerebellar hypoplasias with normal corpus callosum and cerebral
gyri (see above).
normal. The reflexes were hypoactive in the upper and lower
extremities. The Babinsky sign could not be elicited bilater-
ally. There were no signs of spasticity. Muscle tone was nor-
mal in the trunk and extremities.
The patient could easily stand up and walk upright despite
truncal ataxia, but he could not remain upright with his feet
together, eyes open or closed, immediately loses balance and
fall down (Romberg’s negative). He showed additional cere-
bellar signs, such as limb dysdiachokinesia, dysmetria, past-
pointing, excessive rebound, kinetic tremor, trunk titubation,
and inability in tandem gait. His brain MRI scan showed cer-
ebello-vermial hypoplasia (Fig. 1).
Above we described a new case exhibiting all the symp-
toms of UTS, but in contrast to the previous patients this
patient only started to walk on all fours later in childhood.
The previous cases exhibited habitual quadrupedalism,
whereas the present case exhibited facultative quadrupedal-
ism, used only for fast locomotion. These are the main differ-
ences between the previous cases and our patient. Appa-
rently, the patient’s motor system was prepared during his
first 10 years to run economically on all four extremities, and
the slow, uneasy, ataxic, upright gait was replaced by rapid,
easy, and well balanced quadrupedal gait. That is, it took
10 years for rewiring5 of his motor system to create a new
walking style. This suggests any self-organization within the
nervous system6,7 may take a long time to establish a novel
locomotion.

Movement Disorders, Vol. 25, No. 5, 2010

 LETTERS TO THE EDITOR
LEGEND TO THE VIDEO
The video shows late childhood case of UTS: ataxic
upright locomotion, sitting, standing up and running on allfours.
Author Roles: Uner Tan designed and wrote the paper;
Meliha Tan and Sibel Karaca performed the research.
Meliha Tan, MD
Sibel Karaca, MD
Department of Neurology
Baskent University
Adana, Turkey
Uner Tan, MD, PhD*
Department of Physiology
Çukurova University
Adana, Turkey
*E-mail: unertan37@yahoo.com
References
1. Tan U. Unertan syndrome; quadrupedality, primitive language,
and severe mental retardation; a new theory on the evolution of
human mind. Neuro Quantol 2005;4:250–255.
2. Tan U. Evidence for ‘‘Unertan Syndrome’’ and the evolution of
the human mind. Int J Neurosci 2006;116:763–774.
3. Tan U, Pence S, Yilmaz M, Ozkur A, Karaca S, Tan M, Karatas M.
‘‘Unertan Syndrome’’ in two Turkish families in relation to devolu-
tion and emergence of homo erectus: neurological examination,
MRI, and PET scans. Int J Neurosci 2008;118:313–336.
4. Kelly RE. Tripedal knuckle-walking: a proposal for the evolution of
human Locomotion and handedness. J Theor Biol 2001;213:333–358.
5. Miller G. Rewiring faulty circuits in the brain. Science
2009;323:1554–1556.
6. Thelen E, Kelso JAS, Fogel A. Self-organizing systems and infant
motor development. Devel Rev 1987;7:39–65.
7. DeBello WM. Micro-rewiring as a substrate for learning. Trends
Neurosci 2008;31:577–579.
Acute Blepharospasm and Torticollis
Associated with an Ependymoma of the
Lateral Ventricle
Blepharospasm (BL) is a focal dystonia associated with
involuntary eyelid closure due to spasms of the orbicularis
oculi muscles. In most cases, BL is primary and bilateral,
but it may also begin unilaterally. Secondary forms of BL
are rare and are generally associated with lesions of the ba-
sal ganglia, particularly in the lenticular nucleus, the thala-
mus, or the brainstem (mesencephalon). They usually pro-
voke unilateral or asymmetrical BL. They have been associ-
ated with vascular malformation (e.g., cavernoma),
hemorrhage, trauma, demyelination, or parenchymatous tu-
Additional Supporting Information may be found in the online
version of this article.
Potential conflict of interest: Nothing to report.
Published online 3 March 2010 in Wiley InterScience (www.
interscience.wiley.com). DOI: 10.1002/mds.22984
653
mor.1,2 Here, we report the case of a young man with acute
bilateral BL and torticollis, which revealed an ependymoma
of the right lateral ventricle.
A 23-year-old male patient, without personal or familial
medical history, awoke with a bilateral BL corresponding to
nonrhythmic, involuntary, and unpredictable contractions of
the eyelids. The BL was associated with a moderate antecol-
lis. Clinical signs gradually worsened over the next few days.
The rest of his neurological and ophtalmological examination
yielded normal results. The unusual and acute onset in this
young patient suggests a secondary dystonia. Metabolic (Wil-
son’s disease) and iatrogenic (neuroleptic, toxic) etiologies
were eliminated.
Brain magnetic resonance imaging (MRI) showed a well-
circumscribed lesion (21 3 17 3 22 mm) in the right lateral
ventricle body, which appeared enlarged, and a second lesion
(11 3 8 3 7 mm) in the temporal horn of the right lateral
ventricle (Fig. 1). The largest lesion extended to the paren-
chyma, located toward the right caudate nucleus, and the
interthalamic commissure, up to the right thalamus; it had no
invasive feature. No lesion was identified in the brainstem or
in the lenticular nucleus. There was no enhancement by gad-
olinium. A polygraphic surface recording of the face and
neck muscles revealed that most contractions were bilateral
and synchronous and involved both face (orbicularis oculi,
zygomatic) and neck (trapezius, sternocleidomastoideus)
muscles (Supporting Information Figure).
A surgical resection of the intraventricular lesion was
performed, and histopathological analysis identified an epen-
dymoma (grade II). Postoperative MRI confirmed the partial
removal of the lesion and a residual lesion in the right tem-
poral horn. Clinical improvement was observed in the days
following surgery: torticollis was no longer observed, and
eyelid spasms were reduced within 24 hours of the surgical
procedure and remained unchanged 1 year after surgery.
To our knowledge, we describe the first case of acute-
onset focal dystonia in a young man that was associated with
an ependymoma involving the right lateral ventricle and the
head of the right caudate nucleus. So far, only one patient
with unilateral BL secondary to an intraventricular tumor has
been reported.3 The lesion was a ganglioglioma located in
the left lateral ventricle. The appearance of BL as sign of an
identified focal central nervous system lesion remains very
unusual.1,2
Several results should be noted with respect to the
involvement of the basal ganglia in the pathophysiology of
primary BL. First, BL is observed in various basal ganglia
diseases, such as Parkinson’s disease, Huntington’s disease,
progressive supranuclear palsy, and Wilson’s disease.4 In
addition, bilateral activations of the lateral globus pallidus,
caudate nucleus, putamen, and ventral lateral nucleus of the
thalamus have been reported using functional imaging techni-
ques in primary-BL versus non-BL patients, suggesting dys-
function of the motor subcortical loops.5
The quick improvement of symptoms after surgery in our
patient supports a causal link between the tumor and the sec-
ondary BL. Many pathophysiological mechanisms could be
evoked. First, ependymoma or colloid cysts frequently cause
unilateral hydrocephalus by compressing the Monro’s fora-
men.6 Unilateral hydrocephalus could have mechanical con-
sequences: stretching the corticobulbar tracts can cause disin-
hibition of the facial nucleus and the interneurons involved
Movement Disorders, Vol. 25, No. 5, 2010
654 LETTERS TO THE EDITOR

FIG. 1. The MRI showed a well-circumscribed lesion involving the right lateral ventricle, the head of the right caudate nucleus, and a portion of
the adjacent white matter (A) and showed a second smaller lesion in the right temporal horn (B).

in blinking.7 Second, the parenchymateous extension of the du Syste´me Nerveux

ependymoma toward the right caudate nucleus, with its mass Bordeaux, France
effect on the right thalamus, could lead to dysfunction of the Laboratoire Mouvement Adaptation Cognition
cortico-striato-thalamo-cortical loops. To explain the fact Centre National de la Recherche Scientifique (CNRS)
that bilateral blinking could have been induced by a unilat- Unite´ Mixte de Recherche 5227
eral lesion, we hypothesize that eyelid movements may be Universite´ Bordeaux 2
controlled by the nondominant hemisphere, as previously
Bordeaux, France
suggested.2
Finally, this case report suggests that intraventricular *E-mail: virginie.lambrecq@u-bordeaux2.fr
tumors such as ependymoma can be responsible for second-
ary focal dystonia in young adults, highlighting the relevance Igor Sibon, MD, PhD
of neuroimaging diagnostics in unusual clinical presentations Centre Hospitalier Universitaire Pellegrin
of focal dystonia. Service de neurologie
Bordeaux, France
Financial Disclosures: Nothing to report.
Hugues Loiseau, MD
Author Roles: Virginie Lambrecq—conception, organiza- Centre Hospitalier Universitaire Pellegrin
tion, and execution of research project; writing of the first Service de Neurochirurgie
draft of manuscript. Igor Sibon—organization and execution
Bordeaux, France
of research project; review and critique of manuscript.
Hugues Loiseau—organization and execution of research pro-
ject; review and critique of manuscript. Jeannin Séverine— Séverine Jeannin, MD
organization and execution of research project; review and Virginie Dousset, MD
critique of manuscript. Virginie Dousset—organization and Centre Hospitalier Universitaire Pellegrin
execution of research project; review and critique of manu- Service de neurologie
script. Jean-Yves Rotgé—organization and execution of Bordeaux, France
research project; review and critique of manuscript. Domini-
que Guehl—organization and execution of research project; Jean-Yves Rotgé, MD
review and critique of manuscript. Pierre Burbaud—concep- Laboratoire Mouvement Adaptation Cognition
tion, organization, and execution of research project; writing Centre National de la Recherche Scientifique (CNRS)
of the first draft and review and critique of manuscript. Unite´ Mixte de Recherche 5227
Universite´ Bordeaux 2
Bordeaux, France
Virginie Lambrecq, MD* Centre hospitalier Charles Perrens
Centre Hospitalier Universitaire Pellegrin Service de Psychiatrie
Service des Explorations Fonctionnelles Bordeaux, France

Movement Disorders, Vol. 25, No. 5, 2010

 LETTERS TO THE EDITOR
Dominique Guehl, MD, PhD
Pierre Burbaud, MD, PhD
Centre Hospitalier Universitaire Pellegrin
Service des Explorations Fonctionnelles du
Syste´me Nerveux,
Bordeaux, France
Laboratoire Mouvement Adaptation Cognition
Centre National de la Recherche Scientifique (CNRS)
Unite´ Mixte de Recherche 5227
Universite´ Bordeaux 2
Bordeaux, France
References
1. Kostic VS, Sojanovic-Svetel M, Kacar A. Symptomatic dystonias
associated with structural brain lesions: report of 16 cases. Can J
Neurol Sci 1996;23:53–56.
2. Verghese J, Milling C, Rosenbaum DM. Ptosis, blepharospasm
and apraxia of eyelid opening secondary to putaminal hemorrhage.
Neurology 1999;53:652.
3. Yin Foo Lee, Brophy P. Ganglioglioma of the lateral ventricle
presenting with blepharospasm-case report and review of the liter-
ature. J Clin Neurosci 2001;8:279–282.
4. Tolosa E, Compta Y. Dystonia in Parkinson’s disease. J Neurol
2006;253:7–13.
5. Obermann M, Yaldizli O, de Greiff A, Lenard Lachenmayer M,
Buhl A, Maschke M. Morphometric changes of sensorimotor
structures in focal dystonia. Mov disord 2007;22:1117–1123.
6. Gaab MR, Schroeda HW. Neuroendoscopic approach to intraven-
tricular lesions. Neurosurgery 1998;88:496–505.
7. Lang A, Sharpe J. Bleparospasm aasociated with palatal myoclo-
nus and communicating hydrocephalus. Neurology 1984;34:1522–
1524.
Levodopa-Aggravated Lateral Flexion of the
Neck and Trunk as a Delayed Phenomenon of
Unilateral Pallidotomy
We report a patient with early-onset Parkinson’s disease
(PD) who, 5 years after a right-sided pallidotomy, developed
a tonic deviation to the left of the head, the neck, and the
trunk that was markedly aggravated by levodopa (L-dopa).
We suggest that this motor phenomenon may represent a
postoperative dystonia or an L-dopa-potentiated motor asym-
metry and it should be considered a delayed adverse effect of
the neurosurgical procedure.
Our patient first experienced left-sided bradykinesia, rigid-
ity, and rest tremor at the age of 38. The symptoms improved
markedly following L-dopa administration. His right side
became similarly affected 3 years later. He presented motor
fluctuations and hyperkinesias 8 years after the initial PD di-
agnosis. Thirteen years after disease onset, he underwent a
Potential conflict of interest: Nothing to report.
Published online 3 February 2010 in Wiley InterScience (www.
interscience.wiley.com). DOI: 10.1002/mds.22988
655
FIG. 1. Present status of our patient. The head, the neck, and the
trunk appear laterally bent to the left due to increased tone of the
cervical, the dorsal, and the lumbar musculature. A dystonic defor-
mity of the ispilateral hand is also noticed.
right-sided pallidotomy. Four years later, he noticed a lateral
deviation of his head to the left, a drop of his left shoulder
and a dystonic posturing of his left hand. Over the following
months, the postural abnormality progressed to involve the
neck and trunk. The deformity persisted while he was sitting,
lying, or walking, mimicking a left-sided scoliosis (Fig. 1).
Prompted by the observation that the lateral body deviation
was significantly potentiated following L-dopa dosing, we
reduced the total daily L-dopa amount to 150 mg. Although a
considerable improvement was noticed, the postural abnor-
mality never resolved completely. There was no further pro-
gression of this motor phenomenon. Brain MRI revealed a
lesion of the posterioventral right GPi that extended to the
neighboring part of the GPe.
To our knowledge, this is the fourth patient described with
a late development of lateral flexion of the trunk following a
unilateral pallidotomy. The previously reported three patients
had undergone a left-sided pallidotomy and developed a devi-
ation of the spine to the right.1 One of them developed torti-
collis contralaterally to the side of the pallidal lesion, similar
to our patient. Interestingly, all four patients suffered from
early-onset PD and developed the posture deformity years af-
ter the pallidotomy (Table 1). In each of them, the medial
pallidal lesion extended to the internal capsule or the extrer-
nal globus pallidus and/or the putamen.1
Dystonia in PD patients occurs either as an off-period phe-
nomenon related to L-dopa depletion or during on-periods
when it is probably related to excess L-dopa.2 Furthermore,
unilateral restricted pallidal lesions are known to cause con-
tralateral hemidystonia, segmental or focal limb dystonia, and
torticollis.3 As our patient’s symptoms showed no drug
related positive effect and as he indeed had an extended
lesion of the right pallidum, it is possible that the motor de-
formity may be a form of postoperative segmental dystonia.
Movement Disorders, Vol. 25, No. 5, 2010
656 LETTERS TO THE EDITOR

TABLE 1. Characteristics of the four operated PD patients with the neck and/or the trunk lateral deviation
Years from
Age at PD duration on pallidotomy to PD duration on Lesion localization
Present age PD onset pallidotomy symptoms onset symptoms onset based on MRI
Our pt 61 38 13 4 17 GPi/GPe
Pt 1a 72 44 17 8 25 GPi/GPe
Pt 2a 63 47 6 9 15 GPi/Internal Capsule
Pt 3a 69 43 17 4 21 GPi/GPe/Sella Media
Mean 66.3 6 5 43 6 3.7 13.3 6 5.2 6.3 6 2.6 19.5 6 4.4
a
Patients 1, 2, and 3 are reported in Ref. 1.

The aggravation of the lateral body deviation by L-dopa
could represent a motor asymmetry similar to that observed
in rats following a unilateral lesion of the nigrostriatal path-
way.4 In this rotating rat model of Parkinsonism, L-dopa,
given weeks after intracerebral injection of the neurotoxin 6-
Hydroxydopamine, induces a contralateral body rotation asso-
ciated with increased 3H-spiroperidol binding in the lesioned
striatum.4 More recent studies5 have shown that long-term
administration of L-dopa to rats lesioned by 6-Hydroxydopa-
mine alters corticostriatal bidirectional synaptic plasticity. As
such, it is possible that pallidotomy has altered the local ba-
sal ganglia circuitry in our patient, resulting in the L-dopa
aggravated motor asymmetry.
In light of the above, we could conclude that contralateral
deviation of the head, the neck, and/or the trunk can occur as
a delayed adverse event following unilateral pallidotomy.
The extension of the primary medial pallidal lesion to other
neighboring basal ganglia structures could be the underlying
pathogenetic mechanism. In this regard, it is unclear as to
why it takes so many years for the deformity to develop fol-
lowing the neurosurgical procedure, when in other acute
basal ganglia lesions dystonia occurs immediately or shortly
after the destructive event. A long-term postoperational modi-
fication of the basal ganglia physiology, perhaps similar to
that occurring in the rat model of Parkinsonism in which con-
tralateral rotation requires some time to develop following
damage to the nigrostriatal pathway,4 may be implicated. Since
follow-up studies of operated PD patients extend from 1 to 5
years,6,7 it is not surprising that dystonia is never reported as a
postoperative complication of pallidotomy. Follow-up studies
of longer duration are needed to reveal the long-term motor
consequences of this neurosurgical procedure.
Financial Disclosures: Cleanthe Spanaki has been receiv-
ing grants from the Parkinson Disease Foundation and from
the Second Operational Program for Education and Initial
Vocational Training (EPEAEK II) from the Ministry of Edu-
cation of Greece. Spyros Zafeiris has nothing to disclose.
Andreas Plaitakis has been supported by the European Com-
munity and the Ministry of Development/General Secretariat
for Research and Technology (Contract grant number:
PENED 2003/03ED576) and by the Association for the
Advancement of Research and Treatment of Neurologic Dis-
orders of Crete EY ZHN.
Authors Roles: Cleanthe Spanaki: Conception and writing
of the manuscript; Spiros Zafeiris: Taking care of the patient,
providing photographs; Andreas Plaitakis: Conception,
review, and critique of the final manuscript.
Cleanthe Spanaki, MD, PhD*
Spiros Zafeiris, MD
Andreas Plaitakis, MD, PhD
Department of Neurology, University of Crete, Medical
School, Heraklion, Crete, Greece
*E-mail: kliospanaki@yahoo.com
References
1. van de Warrenburg BP, Bhatia KP, Quinn NP. Pisa syndrome af-
ter unilateral pallidotomy in Parkinson’s disease: an unrecognised,
delayed adverse event? J Neurol Neurosurg Psychiatry 2007;78:
329–30; Erattum in J Neurol Neurosurg Psychiatry 2008;79: 337.
2. Tolosa E, Compta Y. Dystonia in Parkinson’s disease. J Neurol
2006;253 (Suppl 7):VII7–VII13.
3. Bhatia KP, Marsden CD. The behavioral and motor consequences of
focal lesions of the basal ganglia in man. Brain 1994;117:859–876.
4. Heikkila RE, Shapiro BS, Duvoisin RC. The relationship between
the loss of dopamine nerve terminals, striatal 3H-spiroperidol bind-
ing and rotational behavior in unilaterally-lesioned rats. Brain Res
1981;211:285–292.
5. Picconi B, Centonze D, Hakansson K, et al. Loss of bidirectional
synaptic plasticity in L-dopa induced dyskinesias. Nat Neurosci
2003;6:501–506.
6. Fine J, Duff J, Chen R, Chir B, Hutchison W, Losano AM, Lang AE.
Long-term follow-up of unilateral pallidotomy in advanced Parkin-
son’s disease. N Engl J Med 2000;342:1708–1714.
7. Strutt AM, Lai EC, Jankovic J, et al. Five-years follow-up of unilat-
eral posteroventral pallidotomy in Parkinson’s disease. Surg Neurol
2009;71:551–558.
GPi-pallidal Stimulation to Treat
Generalized Dystonia in Cockayne
Syndrome
Video
Cockayne syndrome (CS) is a rare autosomal recessive,
progeroid disorder characterized by progressive multisystem
degeneration.1 While neurological impairments usually begin
Additional Supporting Information may be found in the online
version of this article.
Potential conflict of interest: Nothing to report.
Published online 3 February 2010 in Wiley InterScience (www.
interscience.wiley.com). DOI: 10.1002/mds.22992

Movement Disorders, Vol. 25, No. 5, 2010

 LETTERS TO THE EDITOR
FIG. 1. Changes in the Burke-Fahn-Marsden Dystonia Rating Scale (BFM-DRS) subscores before and after surgery. During the 5 month of fol-
low-up period, dystonic symptoms in the craniofacial region, neck, and extremities improve progressively. His total BFM-DRS score, 45 before
treatment (maximum 5 120) decreased to 26.5 (41.1% improvement) at 18 days and to 19.5 (56.7% improvement) at 5 months after the opera-
tion.
in early infancy,1 CS spans a wide range of phenotypical
expressions and a variable clinical course.1,2 We describe our
experience with the use of deep brain stimulation (DBS) for
the bilateral globus pallidus internus (GPi) in a CS patient
associated with generalized dystonia.
The patient, a 52-year-old man with growth failure mani-
festing cognitive disturbance (IQ 5 44), microcephaly (head
circumference 5 48 cm), and low body height (155 cm) and
weight (44 kg) also presented with retinal degeneration, cata-
ract, and sensorineuroal hearing impairment, bilaterally. He
had been born without perinatal complications as the 8th of 9
healthy siblings; however, abnormal growth and cognitive de-
velopment became apparent before he entered elementary
school. Around the age of 30 years, he began to manifest
involuntary movements of his right arm; at the age of 33, he
was placed in a nursing home. At the age of 42, he devel-
oped cervical dystonia (CD). Despite variable medical thera-
pies, such as Clonazepam, Haloperidol, or Trihexyphenidyl
combined with botulinum toxin injections, dystonia spread to
his trunk and lower extremities, making walking difficult.
Progressive CD severely interfered with his eating and he
consequently suffered aspiration pneumonia in April 2008.
On admission to our hospital, the patient received 2 mg/day
of Clonazepam. He exhibited blephalospasm, oromandibular
grimacing, CD with muscular pain, truncal bending and tor-
sion, and dystonic tremor of the extremities. He was unable
to hold out his hands horizontally. He could not grasp his
right hand usefully, and his dystonic tremor and posture also
severely interfered with eating with his left hand (Video
Segment 1).
His preoperative Burke-Fahn-Marsden (BFM)-Dystonia
Rating Scale (DRS) was 45/120 (Fig. 1). Neuroradiological
studies showed extensive atrophy of the cortical and subcorti-
cal structures and the cerebellum without marked calcified
lesions. We proceeded surgery after receiving prior informed
consent from the patient and his family indicating uncertain
outcome.
657
In June 2008, under general anesthesia, he underwent
stereotactic implantation of DBS electrodes (model 3387;
Medtronic) into the bilateral GPi. On the microelectrode
recordings, the background activity was significantly
reduced when the probe was passing through the point 2
mm anterior, 21 mm lateral, and 3 mm ventral to the mid-
point of the anterior–posterior commissure line. Then, the
contact 0 of the DBS electrode was placed at this target
site.
His postoperative course was uneventful. Using the con-
tacts 0 and 1, chronic unipolar stimulation (130 Hz fre-
quency, 450 lsec pulse width) was started with pulse gen-
erators (Soletra, Medtronic) implanted in the subclavian
portion. In the course of 1 month, the amplitude was grad-
ually increased to 2.8 V. Dose of clonazepam was reduced
to 1 mg/day postoperatively. During a 5-month follow-up
period, his dystonic symptoms progressively improved (Fig.
1). His dystonic tremor responded promptly GPi stimula-
tion (Video Segment 2) and his muscular neck and
shoulder pain disappeared within several days. By 1 week
after surgery, he could eat by himself using his left- and
occasionally his right hand (Video Segment 2). The abnor-
mal posture of his trunk did not change (Video Segments
1–3). His BFM-DRS decreased to 26.5/120 (41.1%
improvement) at 18 days and to 19.5/120 (56.7% improve-
ment) at 5 months.
The incidence of movement disorders associated with CS
is not high; however, in their presence, they tend to be re-
fractory to medical therapy.1,3 Progressive pathologic changes
in the basal ganglia-thalamocortical motor loop4 may under-
lie the manifestation of abnormal movements in CS.5
In contrast to primary generalized dystonia, patients with
secondary dystonia experienced less and more variable bene-
fits from GPi-DBS.6 However, it exerted considerable effects
on generalized dystonia secondary to rare neurodegenerative
syndromes such as pantothenate kinase-associated neurode-
generation.7 These findings as well as ours strongly suggest
Movement Disorders, Vol. 25, No. 5, 2010
658 LETTERS TO THE EDITOR
that even patients with decade-long dystonia due to progres-
sive pathological and/or anatomical changes may derive ben-
efits from this treatment.
As previously suggested, that is, phasic forms of dystonia
may have a better improvement with DBS than tonic and
fixed forms, dystonic tremor (and cervical muscular pain)
responded promptly to GPi stimulation in our patient. His
long-lasting spinal deformity might affected his mild but sus-
tained abnormal posturing of the trunk.
Despite the secondary nature of dystonia, GPi-DBS
exerted beneficial effects on daily living activities in our
patient. Although additional case histories must be accumu-
lated and long-term follow-up studies are needed to clarify
optimal indications, our findings suggest DBS as a potential
therapeutic option to treat movement disorders in CS.3
LEGENDS TO THE VIDEO
Segment 1. Preoperatively, the patient manifests continu-
ous right-side dominant dystonic tremor of the extremities.
He cannot hold his hands out horizontally and he is unable to
grasp with his right hand. Note that his cervical and craniofa-
cial dystonia is aggravated by actions tasked to the right
hand (distant part of body). Tonic dystonia in his trunk and
lower extremities interfere with his walk. There is severe in-
terference in eating.
Segment 2. Eighteen days postoperatively, the dystonic
tremor of the extremities disappeared. He can hold up both
hands and use his right hand. Moderate cervical and craniofa-
cial symptoms remain. His walk is steadier and he can eat by
himself using his left- and occasionally his right hand.
Segment 3. After 5 months of continuous GPi stimulation,
he can easily hold up both hands, although mild cervical dys-
tonia is remained. He demonstrates that he can use chop
sticks with his left hand and drink with either hand.
Movement Disorders, Vol. 25, No. 5, 2010
Acknowledgments: This work was supported by a Grant-
in-Aid for Scientific Research from the Ministry of Educa-
tion, Culture, Sports, Science, and Technology of Japan and
a foundation subscribed by Hokuto Hospital, Obihiro, Hok-
kaido, Japan.
Kiyotoshi Hamasaki, MD
Kazumichi Yamada, MD, PhD*
Tadashi Hamasaki, MD, PhD
Jun-ichi Kuratsu, MD, PhD
Department of Neurosurgery
Graduate School of Medical Sciences
Kumamoto University
Kumamoto, Japan
*Email: yamadakazu@fc.kuh.kumamoto-u.ac.jp
References
1. Nance MA, Berry SA. Cockayne syndrome: review of 140 cases.
Am J Med Genet 1992;42:68–84.
2. Tan WH, Baris H, Robson CD, Kimonis VE. Cockayne syndrome:
the developing phenotype. Am J Med Genet 2005;135:214–216.
3. Hebb OM, Guadet P, Mendes I. Deep brain stimulation to treat
hyperkinetic symptoms of Cockayne syndrome. Mov Disord
2006;21:113–115.
4. Eltahawy HA, Saint-Cyr J, Giladi N, Lang AE, Lozano AM. Pri-
mary dystonia is more responsive than secondary dystonia to pal-
lidal interventions: outcome after pallidotomy or pallidal deep
brain stimulation. Neurosurgery 2004;54:613–619.
5. Rapin I, Weidenheim K, Lindenbaum Y, et al. Cockayne syn-
drome in adults: review with clinical and pathologic study of a
new case. J Child Neurol 2006;21:991–1006.
6. Mink JW. The basal ganglia and involuntary movements: impaired inhi-
bition of competing motor patterns. Arch Neurol 2003;60:1365–1368.
7. Castelnau P, Cif L, Valente EM, et al. Pallidal stimulation
improves pantothenate-kinase-associated neurodegeneration. Ann
Neurol 2005;57:738–740.