ObjectivesOptical coherence tomography angiography (OCTA) is widely used for evaluating retinal vessels. The aim of this study was to assess the influence of OCTA quality, as measured by the previously introduced OSCAR-MP criteria, on OCTA outcome parameters and the reliability of test-retest results.MethodsIn this prospective longitudinal cohort study, we performed retinal OCTA at baseline and within 24 hours in 54 participants, including 42 healthy individuals and 12 patients with demyelinating CNS disease. We performed reliability testing on OCTA outcome parameters based on QC status according to the OSCAR-MP criteria.ResultsRetinal vessel density measurements remained consistent between baseline and follow-up scans when both passed quality control. By contrast, vessel densities were significantly higher in high-quality images than in paired lower quality ones. Reliability measures, such as intraclass correlation coefficient (ICC) and Pearson r, were higher in pairs where both images met quality standards, with a lower coefficient of repeatability and minimal detectable change observed.DiscussionPoor OCTA image quality negatively affects retinal vessel density measurements. Implementing OSCAR-MP quality criteria demonstrated strong test-retest reliability in high-quality OCTA images, indicating its potential role as reliable quality criteria for OCTA in future clinical trials and research settings.

OBJECTIVES:Optical coherence tomography angiography (OCTA) is widely used for evaluating retinal vessels. The aim of this study was to assess the influence of OCTA quality, as measured by the previously introduced OSCAR-MP criteria, on OCTA outcome parameters and the reliability of test-retest results. METHODS:In this prospective longitudinal cohort study, we performed retinal OCTA at baseline and within 24 hours in 54 participants, including 42 healthy individuals and 12 patients with demyelinating CNS disease. We performed reliability testing on OCTA outcome parameters based on QC status according to the OSCAR-MP criteria. RESULTS:Retinal vessel density measurements remained consistent between baseline and follow-up scans when both passed quality control. By contrast, vessel densities were significantly higher in high-quality images than in paired lower quality ones. Reliability measures, such as intraclass correlation coefficient (ICC) and Pearson r, were higher in pairs where both images met quality standards, with a lower coefficient of repeatability and minimal detectable change observed. DISCUSSION:Poor OCTA image quality negatively affects retinal vessel density measurements. Implementing OSCAR-MP quality criteria demonstrated strong test-retest reliability in high-quality OCTA images, indicating its potential role as reliable quality criteria for OCTA in future clinical trials and research settings.

While retinal vessel changes are evident in the eyes of patients with relapsing–remitting multiple sclerosis (RRMS), changes in the vasculature of possible MS mimics such as primary Sjögren’s syndrome (pSS) remain to be determined. We investigated the potential of retinal optical coherence tomography (OCT) angiography (OCTA) as diagnostic tool to differentiate between patients with RRMS and pSS. This cross-sectional study included patients with RRMS (n = 36), pSS (n = 36) and healthy controls (n = 30). Participants underwent clinical examination, assessment of visual acuity, retinal OCT, OCTA, and serum markers of glial and neuronal damage. We investigated the associations between OCTA parameters, visual functions, and serum markers. Eyes with a history of optic neuritis (ON) were excluded from analysis. We observed a significant thinning of the combined ganglion cell and inner plexiform layer in the eyes of patients with RRMS but not with pSS, when compared to healthy controls. Retinal vessel densities of the superficial vascular complex (SVC) were reduced in both patients with RRMS and pSS. However, retinal vessel rarefication of the deep vascular complex (DVC) was only evident in patients with pSS but not RRMS. Using multivariate regression analysis, we found that DVC vessel loss in pSS patients was associated with worse visual acuity. Compared to patients with RRMS, rarefication of deep retinal vessels is a unique characteristic of pSS and associated with worse visual function. Assuming a disease-specific retinal vessel pathology, these data are indicative of a differential affliction of the gliovascular complex in the retina of RRMS and pSS patients.

Background and Objectives Optical coherence tomography angiography (OCTA) is a noninvasive high-resolution imaging technique for assessing the retinal vasculature and is increasingly used in various ophthalmologic, neuro-ophthalmologic, and neurologic diseases. To date, there are no validated consensus criteria for quality control (QC) of OCTA. Our study aimed to develop criteria for OCTA quality assessment. Methods To establish criteria through (1) extensive literature review on OCTA artifacts and image quality to generate standardized and easy-to-apply OCTA QC criteria, (2) application of OCTA QC criteria to evaluate interrater agreement, (3) identification of reasons for interrater disagreement, revision of OCTA QC criteria, development of OCTA QC scoring guide and training set, and (4) validation of QC criteria in an international, interdisciplinary multicenter study. Results We identified 7 major aspects that affect OCTA quality: (O) obvious problems, (S) signal strength, (C) centration, (A) algorithm failure, (R) retinal pathology, (M) motion artifacts, and (P) projection artifacts. Seven independent raters applied the OSCAR-MP criteria to a set of 40 OCTA scans from people with MS, Sjogren syndrome, and uveitis and healthy individuals. The interrater kappa was substantial (κ 0.67). Projection artifacts were the main reason for interrater disagreement. Because artifacts can affect only parts of OCTA images, we agreed that prior definition of a specific region of interest (ROI) is crucial for subsequent OCTA quality assessment. To enhance artifact recognition and interrater agreement on reduced image quality, we designed a scoring guide and OCTA training set. Using these educational tools, 23 raters from 14 different centers reached an almost perfect agreement (κ 0.92) for the rejection of poor-quality OCTA images using the OSCAR-MP criteria. Discussion We propose a 3-step approach for standardized quality control: (1) To define a specific ROI, (2) to assess the occurrence of OCTA artifacts according to the OSCAR-MP criteria, and (3) to evaluate OCTA quality based on the occurrence of different artifacts within the ROI. OSCAR-MP OCTA QC criteria achieved high interrater agreement in an international multicenter study and is a promising QC protocol for application in the context of future clinical trials and studies.

Background and Objectives Rarefication of the retinal vasculature as measured by optical coherence tomography angiography (OCT-A) is a novel finding in patients with multiple sclerosis (MS). This study aimed to analyze longitudinal dynamics of the retinal vasculature following an acute inflammatory relapse including acute optic neuritis (ON) and to search for associations with alterations of the retinal architecture and visual function. Methods This prospective longitudinal cohort study included patients with relapsing-remitting MS or clinically isolated syndrome having an acute ON (n = 20) or a non-ON relapse (n = 33). Patients underwent examinations at baseline and after 7, 14, 28, 90, and 180 days with OCT, OCT-A, and assessment of the high- (HCVA) and low-contrast visual acuity (LCVA). Results Retinal vessel loss of the superficial vascular complex (SVC) evolves early after ON and reaches a plateau between 90 and 180 days (relative vessel loss 15% ± 8% [mean ± SD]). In addition, an 18% ± 18% intraindividual increase of the foveal avascular zone (FAZ) is evident within 180 days after acute ON. Both SVC thinning and FAZ enlargement were associated with worse HCVA and LCVA. Rarefication of the SVC evolved simultaneously to thinning of the common ganglion cell and inner plexiform layer (GCIP) after ON. No alterations of the deep vascular complex were seen in eyes with ON, and no alterations of the retinal vasculature were recognized in patients having acute non-ON relapses. Discussion Rarefication of the SVC and growing of the FAZ evolve rapidly after ON and are linked to persistent visual disability. ON-related SVC thinning might be closely linked to GCIP atrophy and might occur due to an altered local metabolic activity within inner retinal layers.

ABSTRACTBackgroundThe long‐term impact of deep brain stimulation (DBS) on Parkinson's disease (PD) is difficult to assess and has not yet been rigorously evaluated in comparison to its natural history.ObjectiveComparison of key disability milestones (recurrent falls, psychosis, dementia, and institutionalization) and death in patients with PD with versus without DBS.MethodsWe collected retrospective information from clinical notes of patients with PD at our center that were implanted with subthalamic DBS >8 years ago (1999–2010) and a control group of PD patients without DBS similar in age at onset, age at baseline, sex distribution, and number of comorbidities at baseline (extracted from a registry study performed in 2004). Cox regression models were used to calculate hazard ratios, adjusted for potential baseline confounding variables (age, sex, disease duration, disease severity, and number of comorbidities).ResultsA total of 74 DBS‐treated and 61 control patients with PD were included. For a median observational period of 14 years, patients treated with DBS were at lower risk of experiencing recurrent falls (hazard ratio = 0.57; 95% confidence interval, 0.37–0.90; P = 0.015) and psychosis (hazard ratio = 0.26; 95% confidence interval, 0.12–0.59; P = 0.001) compared with control patients. There was no significant difference in risk for dementia, institutionalization, or death. Disease progression as assessed by Hoehn and Yahr scores was not slower in DBS‐treated patients.ConclusionsTreatment with chronic subthalamic DBS was associated with lower risk for recurrent falls and psychotic symptoms, effects that may be mediated through improved motor symptom control and reduction in dopaminergic therapies, respectively. There was no evidence for DBS effects on underlying disease progression.

Mutations in the F-BOX only protein 7 (FBXO7) gene have been associated with the development of autosomal-recessive parkinson pyramidal disease (PPD).1 Patients with PPD present with juvenile-onset parkinsonism and variable presence of pyramidal tract signs, ataxia, and dystonia (PARK 15). Parkinsonian symptoms usually show a good and sustained response to levodopa, but early development of drug-induced dyskinesias is common.2 Though invasive therapies such as continuous dopaminergic drug infusions or DBS are standard treatments to control refractory l-dopa-related motor complications in patients with idiopathic Parkinson's disease (PD), there have been no reports on the efficacy and safety of such treatment strategies in symptomatic PARK 15 mutation carriers. We here report on a 21-year-old female PARK 15 patient who required a combination of continuous subcutaneous (SC) infusion of apomorphine and bilateral DBS of the globus pallidus internus (GPi) to control disabling motor fluctuations and dyskinesias. At the age of 16, the patient first noticed clumsiness of her right hand and, within a few months, also developed an impairment of gait with severe postural instability. At age 17, the patient was diagnosed with juvenile PD and therapy with dopamine agonists was initiated, leading to a marked improvement of motor symptoms. After 1 year, adjunct levodopa was needed to maintain satisfactory motor control (l-dopa/carbidopa/entacapone 25/6.25/50 mg 7 times daily, ropinirole 10 mg/day). When the patient first presented to our movement disorders department at the age of 20, she exhibited predictable and unpredictable disabling motor fluctuations. During OFF periods, she showed marked generalized akinesia, was unable to walk without assistance, postural instability led to repetitive falls, and there was severe dystonic dysarthria with marked hypophonic and unintelligible speech. When ON mobility greatly improved and she could walk without assistance, her speech was dysarthric, but easily intelligible, but there were disabling dystonic dyskinesias involving her trunk, neck, and limbs. Dopamine transporter imaging with single-photon emission computed tomography revealed a near complete loss of striatal tracer binding bilaterally. Genetic testing confirmed a homozygeous mutation in the FBXO7 gene. Attempts to increase individual l-dopa doses beyond 50 mg were associated with disabling bouts of dyskinesias whereas frequent dosing of 50 mg every 2 hours was associated with insufficient control of parkinsonism and persistent response fluctuations. (see Video, Segment 1). Treatment with continuous SC infusion of apomorphine (3.1 mg/hour over 16 hours from 6 am to 10 pm) was initiated and led to marked reduction of daily OFF time from approximately 75% of the waking day (score of 4 in the International Parkinson and Movement Disorder Society [MDS]-UPDRS part IV, item 3) to <25% per day (score of 1 in the MDS-UPDRS part IV, item 3). Initially, apomorphine monotherapy was associated with only mild degrees of dyskinesia, but over 6 months there was progressive worsening of predominantly dystonic trunk and neck hyperextension and mixed dystonic and choreic limb movements (score of 4 in the MDS-UPDRS part IV, item 2). Because of the disabling nature of these dystonic ON-period dyskinesias, a DBS procedure targeting the GPi bilaterally was performed after 5 years of disease onset (age 21; electrode model 3387, pulse generator Activa RC; Medtronic, Minneapolis, MN). Electrode location in the posteroventrolateral GPi was confirmed by intraoperative CT. Because the DBS procedure was conducted under general anesthesia, no microelectrode recordings were performed.3 Two days after surgery, stimulation settings were tested and activated (case +, 1-/2-, 9-/10-, 2.9 V, 60 μs, 130 Hz) and there was marked reduction in ON-period dystonic movements within a few days (score of 2 in the MDS-UPDRS part IV, item 2; see Video, Segment 2). Gait improved, such that the patient was able to walk independently for a few steps, but she still suffered from severe postural instability with recurrent falls. Attempts to taper apomorphine led to an immediate reoccurrence of severe motor fluctuations, such that SC apomorphine infusions were eventually continued at slightly reduced doses (3 mg/hour over 16 hours). Combined SC apomorphine infusions and GPi stimulation provided satisfactory motor control over a follow-up time of 6 months. However, severe dysarthria, which was previously mainly associated with OFF periods, progressed to permanent anarthria, which likely reflects disease progression,2 although adverse effects of GPi stimulation cannot be ruled out.4 In conclusion, this case is unusual and instructive in several ways: First, continuous dopaminergic drug delivery by SC apomorphine infusions was initially successful in avoiding disabling dyskinesias previously observed with l-dopa in this case, which appears consistent with current concepts of the pathogenesis of l-dopa-induced dyskinesias in PD. Second, however, this effect was only transient and severe, and disabling, predominantly dystonic dyskinesias recurred despite ongoing apomorphine infusion therapy, showing that continuous drug delivery is not always able to prevent dyskinesias. Finally, this case illustrates that combinations of SC apomorphine infusions and GPi DBS can be useful to control both motor fluctuations and drug-induced dyskinesias in cases of juvenile PD with predominantly dystonic involuntary movements. (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. S.S.: 1A, 1B, 1C, 3A K.S.: 1A, 1B, 1C, 3A E.W.: 1A, 1B, 1C, 3B W.E.: 1A, 1B, 1C, 3B W.P.: 1A, 1B, 1C, 3B Funding Sources and Conflicts of Interest: The authors report no sources of funding and no conflicts of interest. Financial Disclosures for previous 12 months: K.S. reports grants from Oesterreichische Nationalbank, FWF Austrian Science Fund, the Michael J. Fox Foundation, and the MDS and personal fees from the MDS, Boehringer Ingelheim, UCB, Lundbeck, and AOP Orphan Pharmaceuticals AG outside the submitted work. E.W. has received honoraria for speaking and consulting from Medtronic, Novartis, Boehringer Ingelheim, and Schwarz Pharma. W.E. has received speaker's fees from Medtronic. W.P. has received consultancy and lecture fees from AbbVie, AstraZeneca, Teva-Lundbeck, Novartis, GlaxoSmithKline, Boehringer Ingelheim, UCB, Orion Pharma, Merck Serono, and Merz Pharmaceuticals in relation to clinical drug development programs for PD and has received a grant from AstraZeneca. A video accompanying this article is available in the supporting information here. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Menstrual-cycle–related aggravations of parkinsonism resulting from a transient loss of dopaminergic responsiveness in premenopausal women have occasionally been reported in Parkinson's disease (PD). Thus far, underlying mechanisms remain unclear and treatment options are not well established. We present 2 cases of premenopausal sisters with early-onset PD and severe menstrual-cycle–related reduced responsiveness to medication. A 45-year-old woman diagnosed with early-onset PD at the age of 34 presented with akinetic-rigid right-sided parkinsonism. Initially, she was treated with pramipexole 0.35 mg three times daily (TID), which was increased in the first 4 years to 0.7 mg once-daily (QID) and later switched to ropinirole 5 mg QID. During the switch, the patient felt optimally controlled when she was on pramipexole 0.7 mg twice-daily (BID) and ropinirole 5 mg BID and subsequently refused to complete the switch to ropinirole monotherapy. Over the following 2 years on double-agonist therapy, the patient began to notice mild wearing-off fluctuations approximately 3 hours after each dose. Total daily OFF-time was <25% (according to a score of 1 in the International Parkinson and Movement Disorder Society [MDS]-UPDRS part IV, item 3) and disability during OFFs was mild (according to a score of 2 in the MDS-UPDRS part IV, item 4). At the age of 39, after 5 years of agonist treatment, she began to experience marked reductions of drug response up to 5 days before, during, and 3 days after menstruation. Because of worsening of parkinsonism around period times (MDS-UPDRS part III sum score = 25 points) the dose of ropinirole was increased to 5 mg QID and pramipexole 0.7 mg BID was continued. Because of consistent premenstrual aggravation of parkinsonism, the patient was eventually put on gestagen supplementation with dienogest-ethinylestradiol (75 μg) for continuous use. This resulted in a marked improvement of control of parkinsonism also perimenstrually (see Fig. 1). Though she rated herself OFF for at least 75% of the day (according to a score of 4 in the MDS-UPDRS part IV, item 3) preceding gestagen supplementation, this changed to <25% per day (according to a score of 1 in the MDS-UPDRS part IV, item 3) after hormone replacement. A 46-year-old woman, the sister of case 1, was diagnosed with early-onset PD at the age of 37. She presented with mild bradykinesia and left-accentuated mild postural and action tremor. Treatment was initiated with pramipexole 0.35 mg TID, which was increased to 0.7 mg TID within 2 years. One year later, levodopa/benserazide 100/25 mg QID was added because of insufficient motor control. Within 4 weeks after initiation of l-dopa, the patient developed disabling peak-dose dyskinesia (according to 2 points in the MDS-UPDRS part IV, item 1, and to 4 points in the MDS- UPDRS part IV, item 2) and mild wearing-off motor fluctuations with a daily off-time <25% (according to a score of 1 in the MDS-UPDRS part IV, item 3). The addition of amantadine 100 mg QID led to satisfactory improvement of dyskinesias, but wearing-off fluctuations remained troublesome. The patient was eventually reasonably well controlled after switching to l-dopa/carbidopa/entacapone 100/25/200 mg QID and after exchanging pramipexole immediate release with pramipexole extended release 2.1 mg QID. After 6 years of antiparkinsonian treatment, the patient began to experience perimenstrual episodes of pronounced deterioration of motor symptoms (especially tremor) with motor OFF-time occupying more than 75% of waking day (according to a score of 4 in the MDS-UPDRS part IV, item 3, and to an OFF-sum-score of 35 in the MDS-UPDRS part III), accompanied by depressive symptoms with suicidal thoughts and panic attacks. These deteriorations, which started approximately 2 days before menstruation and lasted up to 2 days after menstruation, caused regular consultations of our outpatient clinic. This patient was eventually put on gestagen supplementation with dienogest-ethinylestradiol (75 μg) for continuous use, resulting in a reduction of perimenstrual OFF-time from approximately 75% per day (according to a score of 4 in the MDS-UPDRS part IV, item 3) to <25% per day (according to a score of 1 in the MDS-UPDRS part IV, item 3) without any change in dopaminergic treatment (see Fig. 1). OFF-period related depression and suicidality also subsided. In 2012, at the age of 46, the patient was genetically tested and a homozygous mutation in the intron 6 of the PARK2 gene (c.734 + 1G>A) was found. Menstrual-cycle–related fluctuations in idiopathic PD were first described by Quinn and Marsden in 1986. Similar to our finding, they reported a subjective deterioration of parkinsonism beginning approximately 5 days before and lasting until 2 days after the onset of menses in 11 of 12 female patients.1 Moreover, Thulin et al. found, in up to 75% of women with PD, a worsening of parkinsonian symptoms during menses, even if the menstrual cycle was induced by exogenous hormone administration.2 Also, in postmenopausal women, estrogen-replacement therapy appears to reduce motor disability in patients with motor fluctuations and dyskinesias.3-5 Remarkably, in this population, withdrawal of hormone replacement therapy may result in worsening of parkinsonian symptoms.6 However, in a prospective study including 10 premonopausal women with an average age of 42 and disease duration of 6 years, there seemed to be no correlation between severity of menstrual-related fluctuations and fluctuations in estrogen or progesterone.7 Nevertheless, there is evidence that estrogen might influence PD symptoms and explain gender-specific differences in PD, such as the lower prevalence of PD in females, lower l-dopa requirement, or proneness to dyskinesias in women, compared to men.8-11 The improvement of perimenstrual aggravation of motor symptoms with dienogest-ethinylestradiol supplementation in our cases also suggests that low estrogen levels somehow contributed to reduced responsiveness to dopaminergic treatment during menses. An explanation for the delayed appearance, by approximately 6 years, of these periodic changes of parkinsonism might be the gradual decline of ovarial activity during the fourth decade. Because estrogen signaling seems to be altered in parkin-related PD patients, this might be a target for future therapeutic strategies in this patient population.12 However, the mechanism by which estrogen influences the dopamine system in the short run is still unknown. In conclusion, these two cases demonstrate that hormone replacement by continuous use of a conventional birth control pill can be a treatment option for symptoms caused by a transient perimenstrual loss of dopaminergic responsiveness in premenopausal women with PD. (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique. F.S.S.: 1A, 1B, 1C, 3A K.S.: 1A, 1B, 3B E.W.: 1A, 1B, 3B W.P.: 1A, 1B, 3B Funding Sources and Conflicts of Interest: The authors report no sources of funding and no conflicts of interest. Financial Disclosures for previous 12 months: F.S.S. has received traval grants from AOP-Orphan and Abbvie. K.S. has received honoraria for speaking and consulting from Novartis, Boehringer Ingelheim, Lundbeck, Schwarz Pharma, UCB Pharma, and GlaxoSmithKline (GSK). E.W. has received lecture fees from Medtronic. W.P. has received consultancy and lecture fees from Astra Zeneca, Teva, Novartis, GSK, Boehringer-Ingelheim, UCB, Orion Pharma, and Merck Serono in relation to clinical drug development programs for PD.

Vertical supranuclear gaze palsy (VSGP) is etiologically diverse and can occur in a variety of neurological disorders, including stroke in acute onset cases, whereas a progressive onset is mainly encountered in neurodegenerative conditions such as progressive supranuclear palsy, or metabolic conditions such as Niemann–Pick type C disease [ [1] Leigh R.J. Zee D.S. Diagnosis of central disorders of ocular motility. in: Leigh R.J. Zee D.S. The neurology of eye movements. Oxford University Press, New York1999: 405-610 Google Scholar ]. Iatrogenic VSGP is exceptional and to date only one case of VSGP due to a small hemorrhage at the tip of one electrode was reported after implantation of deep brain stimulation (DBS) for Tourette syndrome [ [2] Ackermans L. Temel Y. Bauer N.J. Visser-Vandewalle V. Dutch-Flemish Tourette Surgery Study GroupVertical gaze palsy after thalamic stimulation for Tourette syndrome: case report. Neurosurgery. 2007; 61: E1100 Crossref PubMed Scopus (31) Google Scholar ]. Here we describe two patients who experienced reversible VSGP as a result of stimulation by misplaced DBS electrodes.

The efficacy of deep brain stimulation (DBS) to treat medically intractable motor complications in advanced Parkinson’s disease (PD) has been established in multiple randomized controlled long-term trials of 6 months duration or longer. These have revealed consistent findings of markedly reduced motor complications and improved quality of life (QoL) as compared with best medical management in advanced PD patients with a mean duration of levodopa treatment usually above 10 years, such that current medical practice is to reserve DBS for those PD subjects with a prolonged history of intractable response oscillations and dyskinesias. 1,2 Recently, Schuepbach et al. 3 investigated the effect of DBS on QoL in PD patients with significantly shorter disease duration and a history of motor complications from Ldopa of 3 years. Their EARLYSTIM trial randomized 251 patients to either DBS plus medical therapy or medical therapy alone demonstrating significant improved QoL, motor disability, activities of daily living, and L-dopa‐induced motor complications in the DBS-treated patients versus those on best medical therapy alone after 2 years of follow-up. The authors suggested to consider earlier use of DBS than is currently reflected by clinical practice and to potentially opt for surgical treatment in patients within the first 3 years after the onset of motor complications. An accompanying editorial to this publication, however, cautioned that the investigated population in the EARLYSTIM trial might only represent a small fraction of PD patients, 4 possibly less than 10%. The authors themselves point out that their study population might not be 100% representative for the general PD population to explain the usually high rate of suicide and suicide attempts during the trial. We sought to better define the percentage of PD patients seen in a tertiary movement disorders center of the type recruited and participating in EARLYSTIM for whom the current trial results might prompt a change in the timing of DBS. For this purpose we retrospectively applied the main inclusion and exclusion criteria of EARLYSTIM to all PD patients seen at the movement disorders center at the Department of Neurology of the Medical University Inns

Background: Deep brain stimulation (DBS) is highly successful in treating Parkinson’s disease (PD), dystonia, and essential tremor (ET). Until recently implantable neurostimulators were nonrechargeable, battery-driven devices, with a lifetime of about 3–5 years. This relatively short duration causes problems for patients (e.g. programming and device-use limitations, unpredictable expiration, surgeries to replace depleted batteries). Additionally, these batteries (relatively large with considerable weight) may cause discomfort. To overcome these issues, the first rechargeable DBS device was introduced: smaller, lighter and intended to function for 9 years. Methods: Of 35 patients implanted with the rechargeable device, 21 (including 8 PD, 10 dystonia, 2 ET) were followed before and 3 months after surgery and completed a systematic survey of satisfaction with the rechargeable device. Results: Overall patient satisfaction was high (83.3 ± 18.3). Dystonia patients tended to have lower satisfaction values for fit and comfort of the system than PD patients. Age was significantly negatively correlated with satisfaction regarding process of battery recharging. Conclusions: Dystonia patients (generally high-energy consumption, severe problems at the DBS device end-of-life) are good, reliable candidates for a rechargeable DBS system. In PD, younger patients, without signs of dementia and good technical understanding, might have highest benefit.

Idiopathic REM sleep behavior disorder (iRBD) has been suggested as an early "pre-motor" stage of Parkinson's disease (PD) in a significant proportion of cases. We investigated autonomic function in 15 consecutive iRBD patients and compared these findings to PD patients and healthy controls. All participants underwent cardiovascular autonomic function testing, and were rated on the COMPASS scale. Symptomatic orthostatic hypotension was present in two iRBD patients, two PD patients and none of the healthy controls. In the tilt table examination, blood pressure changes were similar between iRBD patients and healthy controls. In the PD group, blood pressure drops were more pronounced. In the orthostatic standing test, iRBD patients had higher blood pressure changes than healthy controls. Highest drops were found in PD. Valsalva ratio was lower in iRBD and PD compared to healthy controls. Total COMPASS score was higher in iRBD compared to healthy controls. Highest scores were found in PD. These results support the presence of autonomic dysfunction in iRBD. On several measures, dysfunction was intermediate between healthy controls and PD consistent with the concept that iRBD can be manifestation of synuclein-associated neurodegenerative disorders. Follow-up studies are needed to determine whether iRBD patients with dysfunction on several autonomic domains are at particular risk for developing one of these diseases.

Summary Motor activity in rapid eye movement (REM) sleep behaviour disorder (RBD) has been linked to dream content. Systematic and controlled sleep laboratory studies directly assessing the relation between RBD behaviours and experienced dream content are, however, largely lacking. We aimed to investigate whether a link can be established between RBD behaviours and dream content when both are systematically sampled in a controlled setting. We investigated six patients with Parkinson syndrome and RBD who underwent 2–3 nights of video–polysomnographic recording during which they were awakened from REM sleep (10 min after the onset of the second and successive REM periods). Spontaneous free‐worded dream reports and a structured dream questionnaire were obtained. Video recordings of motor manifestations were each combined with four dream reports, and seven judges had to match the video clip with the correctly reported dream content from a choice of four possibilities. Of the 35 REM sleep awakenings performed, a total of 17 (48.6%) motor‐behavioural episodes with recalled dream content were obtained. The mean of correctly identified video‐dream pairs was 39.5% (range 0–100%). Our data showed that reported dream content can be linked to motor behaviours above chance level. Matching accuracy was affected mainly by the clarity of dream reports and the specific nature of movements manifest in video recordings.

Supernumerary phantom limbs, that is, the awareness of an illusory extra limb is a fascinating neurologic symptom that has been described in a number of neurologic diseases including stroke, spinal injury, and epilepsy. Herein we report a case of a 70-year-old male patient with new-onset focal seizures with left-sided supernumerary phantom arm and leg as the only seizure manifestation. Ictal single-photon emission computed tomography ( SPECT) revealed a hyperperfusion in the right temporoparietal junction and allowed localization of the seizure-onset zone. This report is accompanied by a discussion of phenomenology and terminology in the context of existing literature.

To identify rare causal variants in late-onset Parkinson disease (PD), we investigated an Austrian family with 16 affected individuals by exome sequencing. We found a missense mutation, c.1858G>A (p.Asp620Asn), in the VPS35 gene in all seven affected family members who are alive. By screening additional PD cases, we saw the same variant cosegregating with the disease in an autosomal-dominant mode with high but incomplete penetrance in two further families with five and ten affected members, respectively. The mean age of onset in the affected individuals was 53 years. Genotyping showed that the shared haplotype extends across 65 kilobases around VPS35. Screening the entire VPS35 coding sequence in an additional 860 cases and 1014 controls revealed six further nonsynonymous missense variants. Three were only present in cases, two were only present in controls, and one was present in cases and controls. The familial mutation p.Asp620Asn and a further variant, c.1570C>T (p.Arg524Trp), detected in a sporadic PD case were predicted to be damaging by sequence-based and molecular-dynamics analyses. VPS35 is a component of the retromer complex and mediates retrograde transport between endosomes and the trans-Golgi network, and it has recently been found to be involved in Alzheimer disease.