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✓ The authors describe a technique for performing partial sectioning and myectomy of the trapezius muscle in patients with severe cervical dystonia that is unresponsive to conservative treatment. Asleep-awake-asleep anesthesia allows intraoperative control of the sectioning procedure to avoid causing postoperative weakness of arm elevation above the horizontal plane. The procedure has been performed successfully in three patients. In all cases the dystonic posture of the shoulder and local pain were improved postoperatively. There were no new deficits. This technique can be used as an adjunct to other peripheral surgical procedures in patients with marked laterocollis and dystonic elevation and anteversion of the shoulder.

The expression of adenosine A2a receptors (A2aR) in the mammalian striatum is well known. In contrast the exact distribution of A2aR in other regions of the central nervous system remains unclear. The aim of this study was to investigate the A2aR gene expression in the rat olfactory bulb and spinal cord, two regions which are seldom included in mapping studies. Secondly, we compared the A2aR expression in the rat and in the mouse brain. Hybridization histochemistry was performed with an S35-labelled radioactive oligonucleotide probe. The results show strong expression of A2aR in the mouse and rat striatum in accordance with previous reports. In the olfactory bulb a weak but specific expression of A2aR was found in the granular cell layer in both species. In contrast, no significant expression of the A2aR gene was observed in other parts of the brain or the rat spinal cord. The presence of the A2aR in the mammalian olfactory bulb suggests a functional role for this receptor in olfaction.

Background: Mutations in SCN4A may lead to myotonia. Methods: Presentation of a large family with myotonia, including molecular studies and patch clamp experiments using human embryonic kidney 293 cells expressing wild-type and mutated channels. Results: In a large family with historic data on seven generations and a clear phenotype, including myotonia at movement onset, with worsening by cold temperature, pregnancy, mental stress, and especially after rest after intense physical activity, but without weakness, the phenotype was linked with the muscle sodium channel gene ( SCN4A ) locus, in which a novel p.I141V mutation was found. This modification is located within the first transmembrane segment of domain I of the Na v 1.4 α subunit, a region where no mutation has been reported so far. Patch clamp experiments revealed a mutation-induced hyperpolarizing shift (−12.9 mV) of the voltage dependence of activation, leading to a significant increase (approximately twofold) of the window current amplitude. In addition, the mutation shifted the voltage dependence of slow inactivation by −8.7 mV and accelerated the entry to this state. Conclusions: We propose that the gain-of-function alteration in activation leads to the observed myotonic phenotype, whereas the enhanced slow inactivation may prevent depolarization-induced paralysis.

Mutation in UCH-L1 has been reported as a rare cause of autosomal dominant Parkinson's disease (PD). A S18Y polymorphism in the same gene has been associated with sporadic PD. We investigated the frequency of this polymorphism among the Han-Chinese ethnic population in a case–control study. A total of 600 patients with PD and 334 unrelated healthy controls were genotyped using PCR-restriction fragment length polymorphism analysis. We did not observe any difference in allele or genotype frequencies between the cases and the controls ( P > 0.05). Our results do not support a role for this variant in sporadic PD.

Mutations in the gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been recently linked with autosomal-dominant parkinsonism, and polymorphisms have been commonly associated with sporadic Parkinson's disease (PD). A p.2385GR variant has been reported as a risk factor for PD in Taiwan, Singapore and Japan. Herein, we have assessed the frequency of this polymorphism among the ethnic Han-Chinese population in a case-control study. A total of 600 patients with PD and 334 unrelated healthy controls were genotyped using PCR-restriction fragment length polymorphism analysis. Hardy-Weinberg equilibrium of each group was calculated, and differences in genotype frequencies between groups were assessed by the Chi-square test. In the PD cohort, 70 patients (11.7%) were heterozygous and 1 (0.2%) was homozygous for the p.2385GR variant. This was significantly more frequent than in the controls [3.3%, Odds ratio = 3.9, 95% confidence interval (CI) = 2.1-7.5, P0.01]. Clinically, the age of PD onset of the p.2385GR carriers was lower than the non-carriers (P = 0.01). Our study indicates that this LRRK2 p.2385GR substitution contributes to the development of PD in ethnic Han-Chinese population, which may play important implications for future study on molecular genetics and pathogenesis of PD.

The ontogeny of tyrosine hydroxylase and cholecystokinin gene expression was studied in the rat mesencephalon using hybridization histochemistry. Both transcripts appeared on E13 in the ventrocaudal mesencephalon. The levels of both transcripts increased synchronously during the second half of gestation. The locations of neurons containing either transcript changed similarly during development with a rostral transposition and a lateral extension of the respective areas covered with grains. On the day after birth, the patterns of expression for both genes, although at lower transcript levels, were similar to the patterns seen in the adult.

We describe two Chinese families with a mild form of the myotonia congenita due to novel chloride channel (ClCN1) mutations. In one case, heterozygous I553F and H555N mutations were found. The patient shared the I553F mutation with his healthy father, and his mother had a history of mild myotonia when she was younger. In another family, autosomal dominant myotonia congenita was due to a L844F change. The physiological effects of the mutations were examined by using the two-electrode voltage-clamp technique after expression of the channels in Xenopus oocytes. All mutations drastically shifted the voltage required for half-maximal activation, more under conditions mimicking the homozygous situation, than under conditions mimicking the heterozygous situation. The larger effect was seen in the compound heterozygous situation combining the I553F and the H555N mutations. Our data suggest that myotonia congenita caused by CLCN1 mutations in Chinese have similar variable features to those found in the West.

Hereditary spastic paraplegia (HSP) associated with thin corpus callosum is a rare autosomal recessive neurodegenerative disorder characterized by an abnormally thin corpus callosum, normal motor development, slowly progressive spastic paraparesis and cognitive deterioration. To investigate and localize abnormalities in the brains of two Chinese patients with HSP-TCC, with mutations in the spatacsin gene. Diffusion tensor imaging (DTI) was used to determine the mean diffusion (MD) and fractional anisotropy (FA) in the brains of the patients in comparison to 20 healthy subjects. Voxel-based analysis (VBA) of both the diffusion and anisotropy values were performed using statistical parametric mapping (SPM). Significant changes with MD increase and FA reduction were found in the already known lesions including the corpus callosum, cerebellum and thalamus. In addition, changes were also found in regions that appear to be normal in conventional MRI, such as the brain stem, internal capsule, cingulum and subcortical white matter including superior longitudinal fascicle and inferior longitudinal fascicle. Neither increase in FA nor reduction in MD was detected in the brain. Our study provides clear in vivo MR imaging evidence of a more widespread brain involvement of HSP-TCC. MD is more sensitive than FA in detecting lesions in thalamus and subcortical white matter, suggesting that MD may be a better marker of the disease progression.

OBJECTIVE: Deep brain stimulation (DBS) has emerged as a useful therapeutic option for patients with insufficient benefit from conservative treatment. METHODS: Nine patients with chronic DBS who suffered from cervical dystonia (4), generalized dystonia (2), hemidystonia (1), paroxysmal dystonia (1) and Meige syndrome (1) were available for formal follow-up at three years postoperatively, and beyond up to 10 years. All patients had undergone pallidal stimulation except one patient with paroxysmal dystonia who underwent thalamic stimulation. RESULTS: Maintained improvement was seen in all patients with pallidal stimulation up to 10 years after surgery except in one patient who had a relative loss of benefit in dystonia ratings but continued to have improved disability scores. After nine years of chronic thalamic stimulation there was a mild loss of efficacy which was regained when the target was changed to the pallidum in the patient with paroxysmal dystonia. There were no major complications related to surgery or to chronic stimulation. Pacemakers had to be replaced within 1.5 to 2 years, in general. CONCLUSION: DBS maintains marked long-term symptomatic and functional improvement in the majority of patients with dystonia.

RATIONALE: High levels of calcium independent phospholipase A2 (iPLA2) are present in certain regions of the brain, including the cerebral cortex, striatum, and cerebellum (Ong et al. 2005). OBJECTIVES: The present study was carried out to elucidate a possible role of the enzyme in the motor system. METHODS: The selective iPLA2 inhibitor bromoenol lactone (BEL), the nonselective PLA2 inhibitor methyl arachidonyl fluorophosphonate (MAFP), and an antisense oligonucleotide were used to interfere with iPLA2 activity in various components of the motor system. Control animals received injections of carrier (phosphate buffered saline, PBS) at the same locations. The number of vacuous chewing movements (VCM) was counted from 1 to 14 days after injection. RESULTS: Rats that received BEL and high-dose MAFP injections in the striatum, thalamus, and motor cortex, but not the cerebellum, showed significant increase in VCM, compared to those injected with PBS at these locations. BEL-induced VCM were blocked by intramuscular injections of the anticholinergic drug, benztropine. Increased VCM was also observed after intrastriatal injection of antisense oligonucleotide to iPLA2. The latter caused a decrease in striatal iPLA2 levels, confirming a role of decreased enzyme activity in the appearance of VCM. CONCLUSIONS: These results suggest an important role for iPLA2 in the cortex-striatum-thalamus-cortex circuitry. It is postulated that VCM induced by iPLA2 inhibition may be a model of human parkinsonian tremor.

The S218L CACNA1A mutation has been previously described in two families with familial hemiplegic migraine. We present three siblings with the mutation with the novel association of childhood seizures, and highlight the dynamic changes seen on electroencephalography during hemiplegic migraine attacks. Depressed activity contralateral to the hemiparesis was seen on electroencephalography during acute hemiplegic migraine attacks, which may be due to changes to calcium channels caused by the S218L mutation. Both parents were asymptomatic and did not carry the S218L mutation in their blood. This suggests the presence of mosaicism in the transmitting parent.

Cav2.1 Ca2+ channels (P/Q-type), which participate in various key roles in the central nervous systems by mediating calcium influx, are extensively spliced. One of its alternatively-spliced exon is 37, which forms part of the EF hand. The expression of exon 37a (EFa form), but not exon 37b (EFb form), confers the channel an activity-dependent enhancement of channel opening known as Ca2+-dependent facilitation (CDF). In this study, we analyzed the trend of EF hand splice variant distributions in mouse, rat and human brain tissues. We observed a developmental switch in rodents, as well as an age and gender bias in human brain tissues, suggestive of a possible role of these EF hand splice variants in neurophysiological specialization. A parallel study performed on rodent brains showed that the data drawn from human and rodent tissues may not necessarily correlate in the process of aging.

In a Chinese woman who had diabetes mellitus, undetectable ceruloplasmin, hand tremor, neck dystonia, and cognitive disturbances, genetic analyses revealed a novel homozygous mutation (848G > C or W283S) in exon 5 in the ceruloplasmin gene. Another member with a milder phenotype was also affected by this mutation. The healthy sister was heterozygous at the same position. Aceruloplasminemia has not yet been reported in China. This case suggests that increased awareness should be paid to this disorder in the presence of the typical symptoms.

In the present in situ hybridization and immunocytochemical studies in the mouse central nervous system (CNS), a strong expression of spastin mRNA and protein was found in Purkinje cells and dentate nucleus in the cerebellum, in hippocampal principal cells and hilar neurons, in amygdala, substantia nigra, striatum, in the motor nuclei of the cranial nerves and in different layers of the cerebral cortex except piriform and entorhinal cortices where only neurons in layer II were strongly stained. Spastin protein and mRNA were weakly expressed in most of the thalamic nuclei. In selected human brain regions such as the cerebral cortex, cerebellum, hippocampus, amygdala, substania nigra and striatum, similar results were obtained. Electron microscopy showed spastin immunopositive staining in the cytoplasma, dendrites, axon terminals and nucleus. In the mouse pilocarpine model of status epilepticus and subsequent temporal lobe epilepsy, spastin expression disappeared in hilar neurons as early as at 2h during pilocarpine induced status epilepticus, and never recovered. At 7 days and 2 months after pilocarpine induced status epilepticus, spastin expression was down-regulated in granule cells in the dentate gyrus, but induced expression was found in reactive astrocytes. The demonstration of widespread distribution of spastin in functionally different brain regions in the present study may provide neuroanatomical basis to explain why different neurological, psychological disorders and cognitive impairment occur in patients with spastin mutation. Down-regulation or loss of spastin expression in hilar neurons may be related to their degeneration and may therefore initiate epileptogenetic events, leading to temporal lobe epilepsy.

BACKGROUND: Dystonia is a heterogenous group of movement disorders whose clinical spectrum is very wide. At least 13 different genes and gene loci have been reported. While a 3-bp deletion in the DYT1 gene is the most frequent cause of early limb-onset, generalized dystonia, it has also been found in non-generalized forms of sporadic dystonia. An 18-bp deletion in the DYT1 gene has also been reported. OBJECTIVES: We screened for the 3-bp and 18-bp deletions in the DYT1 gene among our sporadic, adult-onset primary dystonia patients in Singapore. We reviewed the literature to compare the frequency of DYT1 mutation between the East and the West. METHODS: We screened 54 patients with primary dystonia (focal: n=41; segmental: n=11; multifocal: n=1; generalized: n=1) for the deletions in the DYT1 gene. A careful review of all published literature on DYT1 screening among sporadic, non-familial, non-Ashkenazi Jewish patients was done. RESULTS: We did not detect any mutations in the exon 5 of the DYT1 gene in any of our patients. The frequency of DYT1 mutation amongst Asians (1.0%) was comparable to the West (1.56%) (p=NS). CONCLUSIONS: DYT1 mutations are uncommon amongst adult primary dystonia patients in Singapore.

Mutations in CLCN1, the gene encoding the ClC-1 chloride channel in skeletal muscle, lead to myotonia congenita. The effects on the intramembranous channel forming domains have been investigated more than that at the intracellular C-terminus. We have performed a mutation screen involving the whole CLCN1 gene of patients with myotonia congenita by polymerase chain reaction (PCR), single-strand conformation polymorphism studies, and sequencing. Two unrelated patients harbored the same homozygous G-to-T mutation on the donor splice site of intron 17. This led to the skipping of exon 17, as evidenced by the reverse transcriptase PCR. When the exon 17-deleted CLCN1 was expressed in Xenopus oocytes, no chloride current was measurable. This function could be restored by coexpression with the wild-type channel. Our data suggest an important role of this C-terminal region and that exon 17 skipping resulting from a homozygous point mutation in CLCN1 can lead to recessive myotonia congenita.

Der Globus pallidus war eine der ersten Strukturen, welche zur Behandlung von Bewegungsstorungen angegangen wurde. Bereits in den 1940er Jahren fuhrte Meyers Exstirpationen des Globus pallidus uber einen offenen Zugang zur Behandlung von Parkinsonsymptomen durch [54]. Die erste stereotaktische Pallidotomie wurde von Spiegel und Wycis 1948 bei Patienten mit einer Huntingtonerkrankung vorgenommen [66]. In den 1950er Jahren wurden weltweit Tausende von Pallidotomien in erster Linie zur Behandlung der Parkinsonerkrankung durchgefuhrt [33]. Uber den optimalen Zielpunkt im Pallidum bestand damals kein Konsens. Levy verglich die verschiedenen Zielpunkte im Rahmen einer ausfuhrlichen Untersuchung (Abb. 1) [47]. Einige Untersucher wahlten jedoch bereits ein ahnliches Target wie wir es heute verwenden, namlich den sensomotorischen Anteil des Globus pallidus internus (GPi) im posteroventralen lateralen Aspekt dieser Struktur. Die damaligen pathophysiologischen Modelle der Parkinsonerkrankung trugen nur wenig zum Verstandnis der Entstehung der Bradykinese und Akinese bei. Deshalb glaubten viele Untersucher, dass diese Symptome durch einen funktioneilen neurochirurgischen Eingriff entweder nicht beeinflusst werden konnten oder sie sich allenfalls noch verschlechtern wurden. Als 1960 die bedeutende Studie von Svennilson und Kollegen publiziert wurde, wurde sie fast vollstandig ignoriert [68]. Diese Studie berichtete uber 81 Patienten, die zwischen 1951 und 1957 von Leksell mittels einer speziellen bipolaren Elektrode operiert wurden (Abb. 2). Es wurde nicht nur eine Besserung des Rigors und des Tremors beobachtet, sondern auch eine deutliche Besserung der Bradykinese. Als diese Studie veroffentlich wurde, hatten die meisten funktioneilen Neurochirurgen die Pallidotomie jedoch bereits verlassen. Hierfur gab es verschiedene Grunde, unter anderem die zunehmende Verbreitung der Thalamotomie, die Einfuhrung von Levodopa und die damals unzureichenden pathophysiologischen Modelle. Das Pallidum als Zielpunkt zur Behandlung von Bewegungsstorungen wurde von Laitinen Mitte der 1980er Jahre wiederentdeckt [43]. Nach Veroffentlichung seiner Ergebnisse setzte eine Renaissance der funktioneilen Neurochirurgie bei Bewegungsstorungen ein. Zunachst in den Vereinigten Staaten und Skandinavien, spater auch in anderen europaischen und asiatischen Landern, wurden wiederum Tausende von Pallidotomien vorgenommen. Siegfried und Lippitz waren die ersten Untersucher, welche die Prinzipien der tiefen Hirnstimulation (THS) auf den Globus pallidus internus anwendeten [64]. Nachdem sich gezeigt hatte, dass der Nucleus subthalamicus (STN) ebenfalls ein geeigneter Zielpunkt zur Behandlung der Parkinsonerkrankung ist, wurde die STN- Stimulation in den Folgejahren bevorzugt. Dieser Beitrag gibt eine Ubersicht uber die bisherigen klinischen Ergebnisse der THS im GPi bei der Parkinsonerkrankung. Die Vor- und Nachteile im Hinblick auf die STN-Stimulation werden in einem gesonderten Kapitel behandelt.

The aim of this study was to investigate the impact of unilateral deep brain stimulation (DBS) of the ventrointermediate (Vim) thalamic nucleus on neuropsychological functioning comparing stimulation-on with stimulation-off conditions. Nine patients [five patients with Parkinson's Disease (PD), two patients with essential tremor (ET) and 2 patients with multiple sclerosis (MS)] underwent comprehensive neuropsychological testing for cognitive functions, including general mental impairment, aphasia, agnosia, executive and constructional abilities, learning, memory, cognitive processing speed and attention as well as depression. The neuropsychological assessments were performed at least 6 months postoperatively (mean 9 months). Testing in the stimulation-on and stimulation-off condition was obtained within a period of 3 to 4 weeks. Unilateral DBS resulted in improvement of tremor in all patients. There were no significant differences between the stimulation-on and the stimulation-off condition with the exception of a decrement of word-recall in the short delay free-recall subtest of the Rey Auditory-Verbal Learning Test (RAVLT). Subgroup analysis indicated that the impairment in word-recall was related to left-sided thalamic stimulation. Our study confirms that chronic unilateral DBS is a safe method with regard to cognitive function. The subtle changes in episodic memory are related to stimulation per se and not to a microthalamotomy effect.

The human SPG4 locus encodes the spastin gene, which is responsible for the most prevalent form of autosomal dominant hereditary spastic paraplegia (AD-HSP), a neurodegenerative disorder. Here we identify the predicted gene product CG5977 as the Drosophila homolog of the human spastin gene, with much higher sequence similarities than any other related AAA domain protein in the fly. Furthermore we report a new potential transmembrane domain in the N-terminus of the two homologous proteins. During embryogenesis, the expression pattern of Drosophila spastin becomes restricted primarily to the central nervous system, in contrast to the ubiquitous expression of the vertebrate spastin genes. Given this nervous system-specific expression, it will be important to determine if Drosophila spastin loss-of-function mutations also lead to neurodegeneration.

Absence of dystrophin, as found in Duchenne boys, mdx mice and HFMD cats, leads to destabilization of the sarcolemmal-associated protein complex. Gene and cell therapy strategies aim to restore the dystrophin-associated protein complex. In order to better understand the cellular events involved in such therapy in feline and human muscular dystrophy, we asked whether dystrophin-deficient myoblasts would fuse with myoblasts expressing normal dystrophin, and whether the complex would be restored after such a fusion. Cat and human myoblasts were isolated from skeletal muscle of normal subjects and of patients with dystrophin deficiency and proliferated well. After co-culture with normal myoblasts, they fused to form hybrid myotubes. These hybrid myotubes expressed dystrophin, utrophin and dystrophin- associated proteins. Expression of these proteins were restored also in the vicinity of nuclei from dystrophin-deficient donors. These results demonstrate that dystrophin can be expressed and handled normally by hybrid myotubes. They show that myoblasts with a normal dystrophin gene can restore dystrophin expression in dystrophin-deficient myoblasts.

Although sporadic thyrotoxic periodic paralysis (TPP) has a much higher prevalence in Asian than in all the other populations studied so far, it is also increasingly being seen at the emergency departments of the West, hence, it is vital to stress the importance of recognizing it. TPP shares some similarities with hypokalemic periodic paralysis (HOKPP). However, the pathophysiology of TPP and the reasons for this higher incidence are not known. We hypothesized that some mutations in the CACNA1S gene, which has been implicated in familial HOKPP, might play a role in TPP. We present 5 Chinese patients who suffer from TPP and demonstrate typical clinical features. No mutation was found on the whole CACNA1S gene. Therefore other molecular mechanisms will have to be examined in order to explain the different TPP incidences.

Object. The goal of this study was to investigate the efficacy of long-term deep brain stimulation (DBS) of the posteroventral lateral globus pallidus internus (GPi) accomplished using a single-contact monopolar electrode in patients with advanced Parkinson disease (PD). Methods. Sixteen patients suffering from severe PD and levodopa-induced side effects such as dyskinesias and on—off fluctuations were enrolled in a prospective study protocol. There were six women and 10 men and their mean age at surgery was 65 years. All patients underwent implantation of a monopolar electrode in the posteroventral lateral GPi. Initially, nine patients received unilateral stimulation. Three of these patients underwent contralateral surgery at a later time. Ten patients received bilateral stimulation (contemporaneous bilateral surgery was performed in seven patients and staged bilateral surgery in the three patients who had received unilateral stimulation initially). Formal assessments were performed during both off-medication and on-medication (levodopa) periods preoperatively, and at 3 and 12 months postoperatively. There were no serious complications related to surgery or to DBS. Two transient adverse events occurred: in one patient a small pallidal hematoma developed, resulting in a prolonged micropallidotomy effect, and in another patient a subcutaneous hemorrhage occurred at the site of the pacemaker. In patients who received unilateral DBS, the Unified Parkinson's Disease Rating Scale activities of daily living (ADL) score during the off-levodopa period decreased from 30.8 at baseline to 20.4 at 3 months (34% improvement) and 20.6 at 12 months (33% improvement) postoperatively. The motor score during the off period improved from 57.2 at baseline to 35.2 at 3 months (38% improvement) and 35.3 at 12 months (38% improvement) postoperatively. Bilateral DBS resulted in a reduction in the ADL score during the off period from 34.9 at baseline to 22.3 at 3 months (36% improvement) and 22.9 at 12 months (34% improvement). The motor score for the off period changed from 63.4 at baseline to 40.3 at 3 months (36% improvement) and 37.5 at 12 months (41% improvement). In addition, there were significant improvements in patients' symptoms during the on period and in on—off motor fluctuations. Conclusions. Pallidal DBS accomplished using a monopolar electrode is a safe and effective procedure for treatment of advanced PD. Compared with pallidotomy, the advantages of pallidal DBS lie in its reversibility and the option to perform bilateral surgery in one session. Comparative studies in which DBS is applied to other targets are needed.

Objectives: Surgical treatment of complex cervical dystonia and of cervical dyskinesias associated with cervical myelopathy is challenging. In this prospective study, the long term effect of chronic pallidal stimulation in cervical dystonia and on combining the technique with spinal surgery in patients with severe cervical dyskinesias and secondary cervical myelopathy is described. Methods: Eight patients with a history of chronic dystonia who did not achieve adequate benefit from medical treatment or botulinum toxin injection participated in the study. Five patients had complex cervical dystonia with tonic postures and phasic movements. Three patients had rapidly progressive cervical myelopathy secondary to severe cervical dyskinesias and dystonia in the context of a generalised movement disorder. Quadripolar electrodes were implanted in the posteroventral lateral globus pallidus internus with stereotactic CT and microelectrode guidance. In the three patients with secondary cervical myelopathy, spinal surgery was performed within a few weeks and included multilevel laminectomies and a four level cervical corporectomy with spinal stabilisation. Results: Improvement of the movement disorder was noted early after pallidal surgery, but the full benefit could be appreciated only with a delay of several months during chronic stimulation. Three months after surgery, patients with cervical dystonia had improved by 38% in the severity score, by 54% in the disability score, and by 38% in the pain score of a modified version of the Toronto western spasmodic torticollis rating scale. At a mean follow up of 20 months, the severity score had improved by 63%, the disability score by 69%, and the pain score by 50% compared with preoperatively. There was also sustained amelioration of cervical dyskinesias in the three patients who underwent spinal surgery. Lead fractures occurred in two patients. The mean amplitude needed for chronic deep brain stimulation was 3.8 V at a mean pulse width of 210 µs, which is higher than that used for pallidal stimulation in Parkinson's disease. Conclusions: Chronic pallidal stimualtion is effective for complex cervical dystonia and it is a useful adjunct in patients with cervical dyskinesias and secondary cervical myelopathy who undergo spinal surgery.

Huntington’s disease (HD) is a rare genetic brain disorder leading to abnormal movements, cognitive changes and behavioural disturbances. In order to understand the phenotype better, large cohorts of patients with prospective observational data are needed. REGISTRY, launched in 2004 by the European Huntington’s disease Network (EHDN), with the main aims to explore the relationship between clinical characteristics and genetic factors, to expedite identification and recruitment of participants for clinical trials and to develop existing and novel assessment tools to track and predict disease onset and progression. Registry has recruited 11566 participants (75% manifest HD, 15% pre-manifest, 4% at-risk and 6% control participants) at 158 study sites across 20 countries, with data collected by local clinical centres and stored via an internet portal. An extensive range of clinical assessments and biological data are gathered on a wide spectrum of people affected by HD, ranging from those with a positive genetic test but no symptoms through to those with advanced disease. Much knowledge has been gained by analysing the data set. A key strength of Registry, a study strongly supported by lay HD organisations, is its collaborative approach, linking clinicians and scientists, and providing an extensive clinical and biological data repository to facilitate international studies that could not otherwise have been possible. The entire Registry database is available for researchers to conduct data mining projects.

The aim of the study was to investigate force regulation and sequencing of events in Huntington's disease (HD) patients when performing a drawer opening task using the precision grip. Results revealed that HD patients used excessive grip force levels that were unrelated to the actual task demands. Also, they demonstrated a higher grip force value at load force onset in addition to an increased delay between initiation of grip force and load (pulling) force. These data indicate a deficit in the coordinated activation of both forces due to HD. Furthermore, the patients showed bradykinesia along with a prolonged interval between the movement phases underlying the task, denoting an impairment in encoding serially ordered events. Together, these results illustrate the deteriorating effect of striatal pathology on manual function. Accordingly, an amended control of grasping forces and serial encoding of movement-related events due to HD are likely to affect the proficiency of common manipulative skills.

OBJECTIVE To rationalize the technique and reduce the costs associated with chronic deep brain stimulation of the thalamus for treatment of refractory tremor. METHODS The efficacy and safety of a modification in surgical techniques was prospectively assessed in 94 patients with tremor. Bilateral electrodes were implanted in 29 patients, and 65 patients received unilateral implants. Forty-five patients had Parkinson's disease tremor, 42 patients had essential tremor, and 7 patients had kinetic tremors of different causes. In all instances, intraoperative stimulations to analyze the thresholds of intrinsic and extrinsic responses were performed directly with the implanted leads. The electrodes were repositioned until satisfactory results were achieved. The pulse generators were implanted directly after the first step in the same operative session. Patients were not subjected to interoperative test stimulation trials. RESULTS Postoperative improvement of tremor at a mean follow-up of 11.9 months was rated as excellent in 47 patients (50%), marked in 37 patients (39%), moderate in 8 patients (9%), and minor in 2 patients (2%). There was no persistent morbidity related to surgery. In patients with Parkinson's disease, the symptomatic improvement of tremor was rated as excellent in 51% of patients, marked in 36%, moderate in 11%, and minor in 2%. In patients with essential tremor, symptomatic outcome was classified as excellent in 57% of patients, marked in 36%, moderate in 5%, and minor in 2%. Six of the seven patients with kinetic tremor achieved marked symptomatic improvement, and one patient experienced moderate improvement. Forty patients experienced stimulation-related side effects. Side effects were mild in general, and they were reversible with a change in electrical parameters. They occurred more frequently in patients who had bilateral stimulation. CONCLUSION Excellent to marked improvement of tremor is achieved in the majority of patients with physiological target determination via implanted leads in thalamic deep brain stimulation. Interoperative test stimulation trials are unnecessary. Modifications in technique may help to reduce the costs of the related hospital stay.

The authors report the effect of chronic stimulation of the ventrointermediate (Vim) thalamus for treatment of dystonic paroxysmal nonkinesigenic dyskinesias (PNKD). A 37-year-old patient had a 4-year history of severe and painful PNKD of the right arm. Chronic stimulation through a stereotactically implanted monopolar electrode in the left Vim resulted in a decrease of the frequency, duration, and intensity of the dystonic paroxysmal movement disorder. The benefit of stimulation has been maintained over 4 years of follow-up.

Posttraumatic movement disorders remain a controversial issue with focal dystonia being a prominent representative. Focal dystonia of the shoulder without concomittant cervical dystonia is a rare event. We describe 2 patients who, after minor trauma, developed focal dystonia of the shoulder with severe chronic pain. Response to local botulinum toxin A was favorable in 1 patient.

Expression patterns of utrophin were investigated and compared to those of dystrophin and associated proteins in skeletal muscle of rat embryos from E12 to E21 by immunohistochemistry. Utrophin was readily detected from E12 on, earlier than full-length dystrophin on E14. A shorter dystrophin isoform was observed from E12 to E16. The level of utrophin reached a maximum on E16–17 and then declined while that of dystrophin increased after E17. A complementary distribution of these two molecules was observed on E18. Beta-dystroglycan appeared as early as utrophin. Sarcoglycans, appearing from E14 on, were anchored first by utrophin and then by dystrophin. These results elucidate the chronological order of expression of the dytrophin/utrophin protein complex and indicate that this protein complex is originally stabilized by utrophin. This study supports our hypothesis that utrophin might be a developmental precursor of dystrophin.

In three selected patients with severe complex cervical dystonia, continuous bilateral stimulation of the globus pallidus internus was associated with improvement of cervical dystonia, dystonia-associated pain, and functional disability.

The adenosine A2a receptors (A2aR) play an important role in the purinergic mediated neuromodulation. The presence of A2aR in the brain is well established. In contrast, little is known about their expression in the periphery. The purpose of this study was to investigate the expression of A2aR gene in the autonomic (otic, sphenopalatine, ciliary, cervical superior ganglia and carotid body) and in the dorsal root ganglia of normal rat. Hybridization histochemistry with S35-labelled radioactive oligonucleotide probes was used. An expression of A2aR gene was found in the large neuronal cells of the rat dorsal root ganglia. The satellite cells showed no expression of A2aR gene. In the superior cervical ganglion, isolated ganglion cells expressed A2aR. In the carotid body clusters of cells with a strong A2aR gene expression were found. In contrast, the ciliary and otic ganglia did not expressed A2aR gene, and only few small sized A2aR expressing cells were demonstrated in the sphenopalatine ganglion. The discrete distribution of A2aR gene expression in the peripheral nervous system speaks for a role of this receptor in the purinergic modulation of sensory information as well as in the sympathetic nervous system.

The Asp620Asn mutation in the vacuolar protein sorting protein 35 (VPS35) gene and the Arg1205His mutation in the eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) gene were identified in autosomal dominant late-onset familial and sporadic Parkinson disease (PD) patients in a Caucasian population. However, the frequencies of these 2 mutations among Chinese PD patients are unknown. We examined these mutations in a large cohort consisting of 609 PD patients and 600 healthy control subjects from Southwest China. Our results suggest that the Asp620Asn mutation in VPS35 and the Arg1205His mutation in EIF4G1 do not play a role in PD in the Southwest China population. The novel Arg1205Cys mutation in EIF4G1 detected in the current study should be further studied among other Asian patients.

There has been an explosion of knowledge concerning genetic causation of a number of neurological disorders in the last couple of years since the discovery of the gene mutated in Huntington’s disease almost 20 years ago. This has led to the difficulty of making appropriate choice in the use of genetic testing during the diagnostic procedures in such cases. Therefore the European Federation of Neurological Societies (EFNS) has set up a task force to develop guidelines for the general neurologist, and a new series of largely expanded papers has now been published covering the major areas of the field. In this article, the major suggestions established in these guidelines after systematic review of the evidence at hand and experts reaching a consensus are summarised. Currently, there are a number of instances in which molecular testing is of great practical help; however, some instances remain where the place of such a diagnostic tool is not established.

Hyperkinetic movement disorders of facial and neck muscles such as blepharospasm, hemifacial spasm, facial myokimia, and cervical dystonia have rarely been associated with unilateral brainstem or posterior fossa pathologies. We report a case of unilateral cervicofacial dyskinesias due to an ipsilateral petroclival meningioma. A 32 year old left handed woman complained about left sided facial dysaesthesia of the upper quadrant of her face for 1 year. In addition she had intermittent ipsilateral headache. A left sided facial palsy and hypogeusia developed. When progressive hearing loss and persistent ipsilateral tinnitus occurred she sought medical advice. She was referred to our department for further treatment after a large tumour in the left cerebellopontine angle had been demonstrated by MRI. On admission, the left corneal reflex was absent. There was marked hypoaesthesia of the first two divisions of the left trigeminal nerve and a mild left facial palsy. There was also hypogeusia of the left half of the tongue. Speech was slightly …