Severe Dyskinesia Research Articles

Subthalamic deep brain stimulation with a constant-current device in Parkinson's disease: an open-label randomised controlled trial

The effects of constant-current deep brain stimulation (DBS) have not been studied in controlled trials in patients with Parkinson's disease. We aimed to assess the safety and efficacy of bilateral constant-current DBS of the subthalamic nucleus. This prospective, randomised, multicentre controlled trial was done between Sept 26, 2005, and Aug 13, 2010, at 15 clinical sites specialising in movement disorders in the USA. Patients were eligible if they were aged 18-80 years, had Parkinson's disease for 5 years or more, and had either 6 h or more daily off time reported in a patient diary of moderate to severe dyskinesia during waking hours. The patients received bilateral implantation in the subthalamic nucleus of a constant-current DBS device. After implantation, computer-generated randomisation was done with a block size of four, and patients were randomly assigned to the stimulation or control group (stimulation:control ratio 3:1). The control group received implantation without activation for 3 months. No blinding occurred during this study, and both patients and investigators were aware of the treatment group. The primary outcome variable was the change in on time without bothersome dyskinesia (ie, good quality on time) at 3 months as recorded in patients' diaries. Patients were followed up for 1 year. This trial is registered with ClinicalTrials.gov, number NCT00552474. Of 168 patients assessed for eligibility, 136 had implantation of the constant-current device and were randomly assigned to receive immediate (101 patients) or delayed (35 patients) stimulation. Both study groups reported a mean increase of good quality on time after 3 months, and the increase was greater in the stimulation group (4·27 h vs 1·77 h, difference 2·51 [95% CI 0·87-4·16]; p=0·003). Unified Parkinson's disease rating scale motor scores in the off-medication, on-stimulation condition improved by 39% from baseline (24·8 vs 40·8). Some serious adverse events occurred after DBS implantation, including infections in five (4%) of 136 patients and intracranial haemorrhage in four (3%) patients. Stimulation of the subthalamic nucleus was associated with dysarthria, fatigue, paraesthesias, and oedema, whereas gait problems, disequilibrium, dyskinesia, and falls were reported in both groups. Constant-current DBS of the subthalamic nucleus produced significant improvements in good quality on time when compared with a control group without stimulation. Future trials should compare the effects of constant-current DBS with those of voltage-controlled stimulation. St Jude Medical Neuromodulation Division.

Intensive Rehabilitation Treatment in Parkinsonian Patients with Dyskinesias: A Preliminary Study with 6-Month Followup

A major adverse effect of levodopa therapy is the development of dyskinesia, which affects 30–40% of chronically treated Parkinsonian patients. We hypothesized that our rehabilitation protocol might allow a reduction in levodopa dosage without worsening motor performances, thus reducing frequency and severity of dyskinesias. Ten Parkinsonian patients underwent a 4-week intensive rehabilitation treatment (IRT). Patients were evaluated at baseline, at the end of the rehabilitation treatment and at 6-month followup. Outcome measures were the Unified Parkinson's Disease Rating Scale Sections II, III, and IV (UPDRS II, III, IV) and the Abnormal Involuntary Movement Scale (AIMS). At the end of the IRT, levodopa dosage was significantly reduced (P = 0.0035), passing from 1016 ± 327 to 777 ± 333 mg/day. All outcome variables improved significantly (P < 0.0005 all) by the end of IRT. At followup, all variables still maintained better values with respect to admission (P < 0.02 all). In particular AIMS score improved passing from 11.90 ± 6.5 at admission to 3.10 ± 2.3 at discharge and to 4.20 ± 2.7 at followup. Our results suggest that it is possible to act on dyskinesias in Parkinsonian patients with properly designed rehabilitation protocols. Intensive rehabilitation treatment, whose acute beneficial effects are maintained over time, might be considered a valid noninvasive therapeutic support for Parkinsonian patients suffering from diskinesia, allowing a reduction in drugs dosage and related adverse effects.

Evaluation of Neurofeedback Training in the Treatment of Parkinson's Disease: A Pilot Study

We assess the effects of EEG biofeedback training on levodopa-induced dyskinesia (LID) in patients with Parkinson's disease (PD) using a sham feedback controlled study design. Nine subjects were randomized into either a treatment group or control group and underwent 24 sessions of either active feedback training or sham feedback. The training protocol aimed at increasing 8–15 Hz activity while inhibiting excess 4–8 Hz and 23–34 Hz activity at the C3-C4 derivation. There were no statistically significant differences baseline to post-active neurofeedback training as compared to sham feedback training in primary outcome measures assessing change in dyskinesia severity, nor in secondary outcome measures assessing change in clinical features of PD. Nonsignificant trends were observed in subjects’ PD home diaries indicating a decrease in the severity of motor fluctuations. Baseline to post-training comparisons of secondary outcome measures in quantitative EEG analysis showed significant interaction effects with...

Micrographia and related deficits in Parkinson's disease: a cross-sectional study

ObjectivesTo determine the prevalence and clinical features associated with micrographia in Parkinson's Disease (PD).SettingThis study was conducted at a Movement Disorders clinic located in a Veteran Administration Hospital.ParticipantsPD subjects were...

Sustained Response to Deep Brain Stimulation in LRRK2 Parkinsonism with the Y1699C Mutation

Although effective deep brain stimulation of the subthalamic nucleus (STN-DBS) is reported in G2019S leucine-rich repeat kinase 2 (LRRK2) parkinsonism, response to surgery in other LRRK2 mutations has not been previously reported. We present an affected individual from the Lincolnshire pedigree (Y1699C), on whom bilateral STN-DBS was performed to control severe motor fluctuations and dyskinesias. He showed a marked improvement in Unified Parkinson's Disease Rating Scale (UPDRS) Part III scores in the "on" and "off" states, sustained for more than three years. Bilateral STN-DBS in LRRK2-parkinsonism with the Y1699C mutation can be as effective as in sporadic PD.

Subcutaneous Apomorphine Infusion – An Update

Continuous delivery of dopaminergic drugs is an important treatment strategy to delay or reverse motor complications in Parkinson’s disease (PD). Subcutaneous apomorphine (APO) infusion has been shown (in uncontrolled studies) to significantly reduce ‘off’ time and dyskinesia duration and severity, and long-term data show the beneficial effects persist for several years. There is some evidence that the maximum antidyskinetic effect of APO infusion may be attained when oral medications are reduced or discontinued, making monotherapy an important clinical goal. Recent studies demonstrate possible positive effects of APO infusion on the non-motor symptoms of PD. However, more trials are needed to assess the neuropsychiatric effects of this treatment. Moreover, randomised controlled trials are needed to compare APO infusion with best medical treatment and with other invasive treatments such as levodopa/carbidopa intestinal gel infusion and deep brain stimulation.

Neonatal seizures associated with a severe neonatal myoclonus like dyskinesia due to a familial KCNQ2 gene mutation

Mutations in the potassium channel gene KCNQ2, usually cause benign familial neonatal epilepsy. This is an autosomal dominant disorder characterized by clusters of seizures occurring in the first days of life. Most patients have normal psychomotor development and spontaneous remission of seizures by 12 months of age.Since Rett and Teubel reported the first family in 1964 and the identification of KCNQ2 gene mutations in this family by Zimprich et al. in 2006, phenotypic variability has been recognized including: later onset of seizures, myokymia in isolation or accompanied by seizures, neurological deficit and mental retardation.We report a mother and son with an atypical presentation of familial neonatal epilepsy. The mother has persistent epilepsy and subnormal intelligence. The son developed a severe dyskinesia clinically compatible with multifocal myoclonus in the neonatal period that only responded to carbamazepine. He also has ataxia and delayed psychomotor development. EMG revealed a spontaneous occurrence of repetitive normal motor potentials in different muscle groups. Genetic analysis identified a heterozygous missense mutation in KCNQ2 in the child and his mother. ConclusionKCNQ2 mutations can present with a neonatal onset multifocal myoclonus-like dyskinesia.

SIG 2 Perspectives Vol. 21, No. 3, October 2011

SIG 2 Perspectives Vol. 21, No. 3, October 2011

Imaging mass spectrometry reveals elevated nigral levels of dynorphin neuropeptides in L-DOPA-induced dyskinesia in rat model of Parkinson's disease.

L-DOPA-induced dyskinesia is a troublesome complication of L-DOPA pharmacotherapy of Parkinson's disease and has been associated with disturbed brain opioid transmission. However, so far the results of clinical and preclinical studies on the effects of opioids agonists and antagonists have been contradictory at best. Prodynorphin mRNA levels correlate well with the severity of dyskinesia in animal models of Parkinson's disease; however the identities of the actual neuroactive opioid effectors in their target basal ganglia output structures have not yet been determined. For the first time MALDI-TOF imaging mass spectrometry (IMS) was used for unbiased assessment and topographical elucidation of prodynorphin-derived peptides in the substantia nigra of a unilateral rat model of Parkinson's disease and L-DOPA induced dyskinesia. Nigral levels of dynorphin B and alpha-neoendorphin strongly correlated with the severity of dyskinesia. Even if dynorphin peptide levels were elevated in both the medial and lateral part of the substantia nigra, MALDI IMS analysis revealed that the most prominent changes were localized to the lateral part of the substantia nigra. MALDI IMS is advantageous compared with traditional molecular methods, such as radioimmunoassay, in that neither the molecular identity analyzed, nor the specific localization needs to be predetermined. Indeed, MALDI IMS revealed that the bioconverted metabolite leu-enkephalin-arg also correlated positively with severity of dyskinesia. Multiplexing DynB and leu-enkephalin-arg ion images revealed small (0.25 by 0.5 mm) nigral subregions with complementing ion intensities, indicating localized peptide release followed by bioconversion. The nigral dynorphins associated with L-DOPA-induced dyskinesia were not those with high affinity to kappa opioid receptors, but consisted of shorter peptides, mainly dynorphin B and alpha-neoendorphin that are known to bind and activate mu and delta opioid receptors. This suggests that mu and/or delta subtype-selective opioid receptor antagonists may be clinically relevant for reducing L-DOPA-induced dyskinesia in Parkinson's disease.

Extent of pre-operative L-DOPA-induced dyskinesia predicts the severity of graft-induced dyskinesia after fetal dopamine cell transplantation

Graft-induced dyskinesia has emerged as a problematic side effect after transplantation of fetal dopamine cells into the striatum of patients with Parkinson's disease. These adverse effects of dystonic and choreatiform hyperkinesias that persisted even after withdrawal of L-DOPA medication are not yet fully understood, which poses a main obstacle for the re-initiation of neural transplantation in Parkinson's disease. The severity of pre-operative L-DOPA-induced dyskinesia has been proposed as one of several parameters influencing the development of graft-induced dyskinesia. We have therefore characterized graft-induced dyskinesia in the rat model of Parkinson's disease in animals with either mild or severe pre-operative L-DOPA-induced dyskinesia. We show that animals with intrastriatal grafts of fetal dopamine cells and severe pre-operative L-DOPA-induced dyskinesia will reduce their L-DOPA-induced dyskinesia scores by more than 75% but at the same time develop graft-induced dyskinesia of intermediate to strong severity. In contrast, animals with dopamine grafts of similar size but only mild pre-operative L-DOPA-induced dyskinesia also developed graft-induced dyskinesia but this was very mild and of intermediate severity only in a single animal. Severity of pre-operative L-DOPA-induced dyskinesia was correlated with the severity of graft-induced dyskinesia. Our data suggest that patients with no or only mild L-DOPA-induced dyskinesia may carry a lower risk for the development of graft-induced dyskinesia and therefore are better candidates to receive intracerebral grafts of fetal dopamine cells as compared to patients with more pronounced L-DOPA-induced dyskinesia.

DBS Candidates That Fall Short on a Levodopa Challenge Test

Candidacy for deep brain stimulation (DBS) in Parkinson disease (PD) is typically assessed by the preoperative motor response to levodopa along with an interdisciplinary evaluation. However, recent cases treated at our institution have achieved good outcomes with DBS despite a sub-30% improvement in motor scores. The aim of this study was to examine the outcomes of DBS in a subset of patients who failed to reach the 30% motor improvement threshold. A review of all DBS patients treated at the University of Florida Movement Disorders Center between 2002 and 2009 was performed utilizing a DBS database. All patients with sub-30% improvement in Unified Parkinson Disease Rating Scale Part III after dopaminergic medication administration were included. Nine patients were identified; DBS was performed for severe dyskinesia (n=5), "on/off motor" fluctuations (n=1) and medication-refractory tremor (n=3). The target symptoms were improved in all patients. Postoperatively, scores on the Unified Parkinson Disease Rating Scale Part II and III and subscores on Parkinson disease questionnaire-39 improved (P<0.05). Although motor response to levodopa remains the primary selection criteria for DBS candidacy in Parkinson disease, patients who do not meet the 30% threshold and have disabling symptoms may still benefit from DBS. Select patients with severe dyskinesia, "on/off" motor fluctuations, and/or medication-refractory tremor may experience significant benefits from DBS and should be considered on a case by case basis through an interdisciplinary team evaluation.

L-DOPA-induced Dyskinesia is Associated with Regional Increase of Striatal Dynorphin Peptides as Elucidated by Imaging Mass Spectrometry

Opioid peptides are involved in various pathophysiological processes, including algesia, epilepsy, and drug dependence. A strong association between l-DOPA-induced dyskinesia (LID) and elevated prodynorphin mRNA levels has been established in both patients and in animal models of Parkinson's disease, but to date the endogenous prodynorphin peptide products have not been determined. Here, matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) was used for characterization, localization, and relative quantification of striatal neuropeptides in a rat model of LID in Parkinson's disease. MALDI IMS has the unique advantage of high sensitivity and high molecular specificity, allowing comprehensive detection of multiple molecular species in a single tissue section. Indeed, several dynorphins and enkephalins could be detected in the present study, including dynorphin A(1–8), dynorphin B, α-neoendorphin, MetEnkRF, MetEnkRGL, PEnk (198–209, 219–229). IMS analysis revealed elevated levels of dynorphin B, α-neoendorphin, substance P, and PEnk (220–229) in the dorsolateral striatum of high-dyskinetic animals compared with low-dyskinetic and lesion-only control rats. Furthermore, the peak-intensities of the prodynorphin derived peptides, dynorphin B and α-neoendorphin, were strongly and positively correlated with LID severity. Interestingly, these LID associated dynorphin peptides are not those with high affinity to κ opioid receptors, but are known to bind and activate also μ- and Δ-opioid receptors. In addition, the peak intensities of a novel endogenous metabolite of α-neoendorphin lacking the N-terminal tyrosine correlated positively with dyskinesia severity. MALDI IMS of striatal sections from Pdyn knockout mice verified the identity of fully processed dynorphin peptides and the presence of endogenous des-tyrosine α-neoendorphin. Des-tyrosine dynorphins display reduced opioid receptor binding and this points to possible novel nonopioid receptor mediated changes in the striatum of dyskinetic rats. Because des-tyrosine dynorphins can only be detected by mass spectrometry, as no antibodies are available, these findings highlight the importance of MALDI IMS analysis for the study of molecular dynamics in neurological diseases.

Characterization of 3,4-Methylenedioxymethamphetamine (MDMA) EnantiomersIn Vitroand in the MPTP-Lesioned Primate:R-MDMA Reduces Severity of Dyskinesia, WhereasS-MDMA Extends Duration of ON-Time

l-3,4-dihydroxyphenylalanine (l-DOPA) is the most effective treatment for Parkinson's disease, but long-term l-DOPA administration is marred by the emergence of motor complications, namely, dyskinesia and a shortening of antiparkinsonian benefit (wearing-OFF). 3,4-methylenedioxymethamphetamine (MDMA) is unique in that it exerts antidyskinetic effects and may enhance antiparkinsonian actions of l-DOPA. MDMA is composed of two enantiomers with different pharmacological profiles; here, we describe a novel enantiospecific synthesis of the two enantiomers and expand on the previous characterization of their pharmacology. R-MDMA (rectus-MDMA) is relatively selective for 5-HT(2A) receptors, whereas S-MDMA (sinister-MDMA) inhibits both serotonin (SERT) and dopamine transporters (DAT; SERT/DAT ratio of 10 to 1). R- or S-MDMA (1, 3, and 10 mg/kg, s.c.) was administered in combination with l-DOPA (15 mg/kg, s.c.) to six female common marmosets (Callithrix jacchus) rendered parkinsonian by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) administration. Motor disability, including parkinsonism and dyskinesia, and duration of antiparkinsonian benefit (ON-time) were evaluated. After the administration of R-MDMA (3 and 10 mg/kg), the severity of peak-dose dyskinesia was decreased (by 33 and 46%, respectively; p < 0.05); although total ON-time was unchanged (approximately 220 min), the duration of ON-time with disabling dyskinesia was decreased by 90 min when compared to l-DOPA alone (69% reduction; p < 0.05). S-MDMA (1 mg/kg) increased the total ON-time by 88 min compared to l-DOPA alone (34% increase; p < 0.05), though dyskinesia were exacerbated. These data suggest that racemic MDMA exerts simultaneous effects, reducing dyskinesia and extending ON-time, by 5-HT(2A) antagonism and SERT-selective mixed monoamine uptake inhibition, which arise from its R and S enantiomers, respectively.

AFQ056 treatment of levodopa‐induced dyskinesias: Results of 2 randomized controlled trials

Study objectives were to assess the efficacy, safety, and tolerability of AFQ056 in Parkinson's disease patients with levodopa-induced dyskinesia. Two randomized, double-blind, placebo-controlled, parallel-group, in-patient studies for Parkinson's disease patients with moderate to severe levodopa-induced dyskinesia (study 1) and severe levodopa-induced dyskinesia (study 2) on stable dopaminergic therapy were performed. Patients received 25-150 mg AFQ056 or placebo twice daily for 16 days (both studies). Study 2 included a 4-day down-titration. Primary outcomes were the Lang-Fahn Activities of Daily Living Dyskinesia Scale (study 1), the modified Abnormal Involuntary Movement Scale (study 2), and the Unified Parkinson's Disease Rating Scale-part III (both studies). Secondary outcomes included the Unified Parkinson's Disease Rating Scale-part IV items 32-33. The primary analysis was change from baseline to day 16 on all outcomes. Treatment differences were assessed. Fifteen patients were randomized to AFQ056 and 16 to placebo in study 1; 14 patients were randomized to each group in study 2. AFQ056-treated patients showed significant improvements in dyskinesias on day 16 versus placebo (eg, Lang-Fahn Activities of Daily Living Dyskinesia Scale, P = .021 [study 1]; modified Abnormal Involuntary Movement Scale, P = .032 [study 2]). No significant changes were seen from baseline on day 16 on the Unified Parkinson's Disease Rating Scale-part III in either study. Adverse events were reported in both studies, including dizziness. Serious adverse events (most commonly worsening of dyskinesias, apparently associated with stopping treatment) were reported by 4 AFQ056-treated patients in study 1, and 3 patients (2 AFQ056-treated patient and 1 in the placebo group) in study 2. AFQ056 showed a clinically relevant and significant antidyskinetic effect without changing the antiparkinsonian effects of dopaminergic therapy. © 2011 Movement Disorder Society.

The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis

BackgroundSubmicroscopic deletions in 14q12 spanning FOXG1 or intragenic mutations have been reported in patients with a developmental disorder described as a congenital variant of Rett syndrome. This study aimed to...

Chronic acquired hepatocerebral degeneration: effects of liver transplantation on neurological manifestations

Three cirrhotic patients with chronic acquired hepatocerebral degeneration (CAHD) received neurologic, neuropsychologic and neuroimaging assessment before and after liver transplantation (LT). Before transplantation, neurologic dysfunction consisted in severe bradykinesia, dystonia, dyskinesia, ataxia and dysarthria. Cognitive impairment affected mainly attentional and executive domains. Brain MRI showed bilateral hyperintensities of the basal ganglia on T1-weighted images. After transplantation, motor manifestations promptly resolved. Cognitive testing showed a major improvement in two patients, whereas cognitive performances were slightly worsened in the third, reasonably due to the effects of a head injury before LT and a tacrolimus-related encephalopathy arising early after LT. MRI images 12 months later showed a slight reduction of the previously disclosed abnormalities in all three patients. None of them experienced recurrence of CAHD. Our observation reinforces the assumption that surgery is the best treatment option for CAHD and that severe neurological impairment in CAHD should not be considered a contraindication for LT.

Lingual Dyskinesia and Tics: A Novel Presentation of Copper-Metabolism Disorder

Copper is a trace element that is required for cellular respiration, neurotransmitter biosynthesis, pigment formation, antioxidant defense, peptide amidation, and formation of connective tissue. Abnormalities of copper metabolism have been linked with neurologic disorders that affect movement, such as Wilson disease and Menkes disease; however, the diagnosis of non-Wilson, non-Menkes-type copper-metabolism disorders has been more elusive, especially in cases with atypical characteristics. We present here the case of an adolescent with a novel presentation of copper-metabolism disorder who exhibited acute severe hemilingual dyskinesia and prominent tics, with ballismus of the upper limbs, but had normal brain and spinal MRI results and did not show any signs of dysarthria or dysphagia. His serum copper and ceruloplasmin levels were low, but his urinary copper level was elevated after penicillamine challenge. We conclude that copper-metabolism disorders should be included in the differential diagnosis for movement disorders, even in cases with highly unusual presentations, because many of them are treatable. Moreover, a connection between copper-metabolism disorders and tics is presented, to our knowledge, for the first time in humans; further investigation is needed to better establish this connection and understand its underlying pathophysiology.

Movement disorders in nonpsychotic siblings of patients with nonaffective psychosis

Movement disorders such as dyskinesia and Parkinsonism have frequently been reported in (drug-naïve) patients with nonaffective psychosis. Therefore movement disorders may be related to schizophrenia. Siblings of patients with nonaffective psychosis also appear to have subtle forms of movement disorders. This suggests that motor abnormalities may also be related to the risk of developing the disease. Subtle forms are not always detected with the use of the standard observation-based clinical rating scales, which are less sensitive than mechanical instrument measurement. This study compared the presence and severity of dyskinesia and Parkinsonism in 42 non-psychotic siblings of patients with nonaffective psychosis and in 38 controls as measured by mechanical instruments and clinical rating scales. There were no significant differences in movement disorders between siblings and controls on the basis of clinical assessments. However, mechanical measurements indicated that siblings compared to controls displayed significantly more dyskinesia and Parkinsonism signs. These results suggest that motor signs could be markers of vulnerability for psychosis or schizophrenia. In addition this study shows that mechanical instrument measurement of movement disorders is more sensitive than assessment with clinical rating scales. Therefore, it may be used in screening programs for populations at risk for psychosis.

The prevalence and clinical characteristics of punding in Parkinson's disease

Punding (the display of stereotyped, repetitive behaviors) is a relatively recently discovered feature of Parkinson's disease (PD). Little is known about the prevalence and clinical characteristics of punding in PD. In this review, four large scientific databases were comprehensively searched for literature in relation to punding prevalence and clinical correlates in the context of PD. Prevalence was found to vary greatly (between 0.34 to 14%), although there were large disparities in study populations, assessment methods, and criteria. We observed an association between punding, dopaminergic medications, and impulse control disorder. Other characteristics, which may be more common among punders, include a higher severity of dyskinesia, younger age of disease onset, longer disease duration, and male gender. More research in large clinical datasets is required in many areas before conclusions are drawn. The pathophysiology behind the punding phenomenon is also poorly understood at present, rendering it difficult to develop targeted therapy. The current mainstay of treatment is the reduction in the dose of dopaminergic medications, the evidence for other suggested therapies being purely empirical.

Tiefe Hirnstimulation bei Morbus Parkinson mit Kamptokormie? Ein Fallbericht

Camptocormia is recognised as a severe postural movement disorder complicating neurodegenerative diseases like Parkinson's disease (PD) and multisystem atrophy. Pathophysiologically two main hypotheses are discussed: (i) a disorder of the basal ganglia resulting in axial dystonia and rigidity on the one hand and (ii) an extensor truncal myopathy on the other hand. Therapeutic efforts often result in limited success. Therefore, reports on improvements by deep brain stimulation (DBS) are of great interest. However, the role of DBS in the treatment of camptocormia remains unclear. Here, we report a female PD patient who responded well to DBS of the subthalamic nucleus for severe dyskinesias and fluctuations. However, after 6 months she started to develop a rapidly progressing camptocormia which did not respond to DBS. The clinical and electrophysiological examination suggested a truncal erector myopathy. The inconsistent reports on the effects of DBS on camptocormia in PD patients suggest heterogeneous pathogenetic pathways. A pathophysiological subtype with predominant basal ganglia dysfunction and responsivity to DBS, however, seems to be rather rare. A myopathy, in contrast, seems to be more frequent and DBS is not effective in this condition. Therefore, camptocormia in PD patients is not an established indication for DBS.