Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients With Synucleinopathies.

Importance: Finding a reliable diagnostic biomarker for the disorders collectively known as synucleinopathies (Parkinson disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA], and pure autonomic failure [PAF]) is an urgent unmet need. Immunohistochemical detection of cutaneous phosphorylated α-synuclein may be a sensitive and specific clinical test for the diagnosis of synucleinopathies. Objective: To evaluate the positivity rate of cutaneous α-synuclein deposition in patients with PD, DLB, MSA, and PAF. Design, Setting, and Participants: This blinded, 30-site, cross-sectional study of academic and community-based neurology practices conducted from February 2021 through March 2023 included patients aged 40 to 99 years with a clinical diagnosis of PD, DLB, MSA, or PAF based on clinical consensus criteria and confirmed by an expert review panel and control participants aged 40 to 99 years with no history of examination findings or symptoms suggestive of a synucleinopathy or neurodegenerative disease. All participants completed detailed neurologic examinations and disease-specific questionnaires and underwent skin biopsy for detection of phosphorylated α-synuclein. An expert review panel blinded to pathologic data determined the final participant diagnosis. Exposure: Skin biopsy for detection of phosphorylated α-synuclein. Main Outcomes: Rates of detection of cutaneous α-synuclein in patients with PD, MSA, DLB, and PAF and controls without synucleinopathy. Results: Of 428 enrolled participants, 343 were included in the primary analysis (mean [SD] age, 69.5 [9.1] years; 175 [51.0%] male); 223 met the consensus criteria for a synucleinopathy and 120 met criteria as controls after expert panel review. The proportions of individuals with cutaneous phosphorylated α-synuclein detected by skin biopsy were 92.7% (89 of 96) with PD, 98.2% (54 of 55) with MSA, 96.0% (48 of 50) with DLB, and 100% (22 of 22) with PAF; 3.3% (4 of 120) of controls had cutaneous phosphorylated α-synuclein detected. Conclusions and Relevance: In this cross-sectional study, a high proportion of individuals meeting clinical consensus criteria for PD, DLB, MSA, and PAF had phosphorylated α-synuclein detected by skin biopsy. Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of phosphorylated α-synuclein in clinical care.

The effects of treatment with pimavanserin on activities of daily living in patients with Parkinson's disease psychosis: a 16-week, single-arm, open-label study.

Background: More than half of patients with Parkinson's disease will experience psychosis symptoms in the form of hallucinations or delusions at some point over the course of their disease. These symptoms can significantly impact patients' health-related quality of life, cognitive abilities, and activities of daily living (ADLs) and function. Clinical assessment of how psychosis impacts these measures is crucial; however, few studies have assessed this sufficiently, in part due to a lack of appropriate scales for comprehensively assessing function. Objective: The objective was to assess how symptoms of Parkinson's disease psychosis (PDP) impact ADLs and function, cognitive function, and health-related quality of life. Design: To address this unmet need, we utilized a modified version of the Functional Status Questionnaire (mFSQ) to measure the impact of psychosis on ADLs and function in patients with PDP treated with pimavanserin, a US Food and Drug Administration-approved medication to treat hallucinations and delusions associated with PDP. Methods: Eligible patients entered a 16-week, single-arm, open-label study of oral pimavanserin (34 mg) taken once daily. The primary endpoint was change from baseline to Week 16 on the mFSQ. Secondary endpoints included the Movement Disorders Society-modified Unified Parkinson's Disease Rating Scale (MDS-UPDRS) I and II; Schwab and England ADL; Clinical Global Impression-Severity of Illness (CGI-S), Clinical Global Impression-Improvement (CGI-I), and Patient Global Impression-Improvement (PGI-I), and were also measured as change from baseline to Week 16 using mixed-effects model for repeated measures (MMRM) and least-squares mean (LSM). Results: Our results in a proof-of-concept, 16-week, open-label clinical study in 29 patients demonstrated that an improvement in psychosis symptoms following treatment with pimavanserin was associated with improvements in multiple measures of ADLs and function. Notably, a significant improvement was found on the primary endpoint, change from baseline to Week 16 in mFSQ score [LSM [SE] 14.0 [2.50], n = 17; 95% CI (8.8, 19.3); p < 0.0001]. Conclusion: These findings highlight the potential for improvement in function with improvement of psychosis symptoms in patients with PDP and suggest that the mFSQ may be a measurement tool to evaluate the level of improvement in function. Trial registration: ClinicalTrials.gov Identifier: NCT04292223.

X-Linked Dystonia-Parkinsonism ("Lubag") May Present with Peripheral Synucleinopathy.

BACKGROUND: X-linked dystonia parkinsonism (XDP) or "Lubag" is a genetic dystonia syndrome observed among Filipinos that can present with levodopa-responsive parkinsonism and abnormal dopamine transporter (DAT) imaging. OBJECTIVE: The aim of this study is to describe the results of skin biopsies for phosphorylated α-synuclein (P-SYN) in XDP. METHOD: This study used the retrospective chart review. RESULTS: We report 6 patients who carried the XDP gene mutation with DAT imaging and skin biopsies to detect P-SYN. Five had segmental or multifocal dystonia and parkinsonism: 4 were levodopa-responsive and 1 non-levodopa-responsive. One patient was asymptomatic but had mild bradykinesia. Cutaneous P-SYN and abnormal DAT scans were noted in the 4 levodopa-responsive patients and 1 asymptomatic patient. CONCLUSION: We report for the first time the presence of cutaneous P-SYN in XDP. Our findings suggest that XDP may be a hitherto-undescribed synucleinopathy or that some XDP patients may have concurrent Parkinson's disease.

Direct targeting of the ventral intermediate nucleus of the thalamus in deep brain stimulation for essential tremor: a prospective study with comparison to a historical cohort.

OBJECTIVE: The ventral intermediate nucleus of the thalamus (VIM) is an effective target for deep brain stimulation (DBS) to control symptoms related to essential tremor. The VIM is typically targeted using indirect methods, although studies have reported visualization of the VIM on proton density-weighted MRI. This study compares the outcomes between patients who underwent VIM DBS with direct and indirect targeting. METHODS: Between August 2013 and December 2019, 230 patients underwent VIM DBS at the senior author's institution. Of these patients, 92 had direct targeting (direct visualization on proton density 3-T MRI). The remaining 138 patients had indirect targeting (relative to the third ventricle and anterior commissure-posterior commissure line). RESULTS: Coordinates of electrodes placed with direct targeting were significantly more lateral (p < 0.001) and anterior (p < 0.001) than those placed with indirect targeting. The optimal stimulation amplitude for devices measured in voltage was lower for those who underwent direct targeting than for those who underwent indirect targeting (p < 0.001). Patients undergoing direct targeting had a greater improvement only in their Quality of Life in Essential Tremor Questionnaire hobby score versus those undergoing indirect targeting (p = 0.04). The direct targeting group had substantially more symptomatic hemorrhages than the indirect targeting group (p = 0.04). All patients who experienced a postoperative hemorrhage after DBS recovered without intervention. CONCLUSIONS: Patients who underwent direct VIM targeting for DBS treatment of essential tremor had similar clinical outcomes to those who underwent indirect targeting. Direct VIM targeting is safe and effective.

Thalamic Deep Brain Stimulation May Improve Restless Legs Syndrome in Patients With Essential Tremor.

OBJECTIVES: To determine change in restless legs syndrome (RLS) symptoms in essential tremor (ET) patients undergoing bilateral thalamic ventral intermedius (VIM) deep brain stimulation (DBS) surgery. MATERIALS AND METHODS: We retrospectively reviewed our database of ET patients with RLS who had undergone VIM DBS for tremor from 2012 to 2020. We reviewed the patients with available International Restless Leg Syndrome Study Group RLS scale scores before and after DBS. Percentage of responders, defined as proportion of patients experiencing three or more point improvement of RLS scores post-DBS, was calculated. We performed two-tailed t-test of pre-DBS and post-DBS RLS scores. RESULTS: We identified 13 patients with ET and RLS who had undergone bilateral VIM DBS, of whom nine (69%) were responders post-DBS. Five of 13 patients (38%) had complete resolution of RLS post-DBS. For all patients, mean pre-DBS RLS score was 15.8 ± 7.9 which improved by 46% post-DBS to a mean of 8.5 ± 8.8 (p = 0.007). Four patients rated their RLS scale one night with the stimulator OFF and another night with the stimulator ON. The mean RLS score with stimulator ON was 15.5 ± 7.6 which improved by 53% to a mean of 6.25 ± 7.8 (p = 0.008), with two having complete resolution of RLS with stimulator ON. Of the nine responders, six preferred to keep their stimulator ON at night due to relief of RLS and better subjective quality of sleep. CONCLUSIONS: We report for the first time improvement of RLS in patients with ET after bilateral thalamic DBS. Although many ET patients with nonrechargeable DBS systems switch off their stimulator at night to conserve battery life, those with RLS may potentially benefit from keeping their stimulator ON at night to relieve their RLS.

Tardive Blepharospasm May Respond to Bilateral Pallidal Deep Brain Stimulation.

Background: To date, there have been no reports of tardive blepharospasm being treated with deep brain stimulation (DBS), though there have been two reports of focal blepharospasm responding favorably to bilateral pallidal DBS. Case: A 34 year old man with tardive blepharospasm that was refractory to oral medications as well as botulinum toxin types A and B underwent bilateral pallidal DBS under general anesthesia. He had significant improvement of his severe blepharospasm by one and half months post-DBS which was sustained at last follow-up 30 months post-DBS. The best programming parameters included pulse widths of 90-100 µsec, frequencies of 140-150 Hz, and stimulating the ventral contacts in each side. Conclusion: Our case represents the first report of medically refractory tardive blepharospasm responding favorably to bilateral pallidal DBS.

Short-Lasting Unilateral Neuralgiform Headache With Conjunctival Injection and Tearing (SUNCT) Improves With Bilateral Ventral Tegmental Area Deep Brain Stimulation.

BACKGROUND: Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a severe headache disorder characterized by clustered episodes of extreme pain. Refractory to most interventions, ipsilateral unilateral ventral tegmental area (VTA) deep brain stimulation (DBS) has been previously reported to be efficacious in 14 cases. METHODS AND RESULTS: Herein, we report the first case of an individual with medically refractory SUNCT who underwent bilateral VTA DBS. The patient experienced better improvement of his headaches with bilateral stimulation compared to unilateral stimulation. He also had a return of severe headaches within a few hours after his stimulator was switched off during sleep, with rebound worsening of his headaches over several days. The main side effects were double vision and difficulty focusing while reading, which were observed primarily with unipolar stimulation that required high voltages, high frequencies, and multiple negative contacts to control the headaches. The side effects were minimized with bipolar and interleaving stimulation with comparable control of his headaches. CONCLUSION: Bilateral VTA DBS may be effective in alleviating medical refractory SUNCT.

Adductor Spasmodic Dysphonia Improves with Bilateral Thalamic Deep Brain Stimulation: Report of 3 Cases Done Asleep and Review of Literature.

Background: To date, there are only six published reports of adductor spasmodic dysphonia (SD) responding to awake thalamic deep brain stimulation (DBS). Methods: We retrospectively reviewed cases of Essential Tremor (ET) with SD that were seen in our center from 2012 to 2020. We further identified those that have undergone thalamic DBS, and had a blinded laryngologist rate first the audio voice recordings before and after DBS using the Unified Spasmodic Dysphonia Rating Scale (USDRS), and the video recordings last to rate the related movements and facial grimacing. Results: We identified three cases of adductor SD with ET that had undergone bilateral ventralis intermedius (VIM) DBS under general anesthesia. All patients noted improvement of their limb and voice tremor, as well as their SD post-DBS. Although improvement of tremor was observed even with initial programming in all three, improvement of SD was noted only upon reaching higher amplitudes or wider pulse widths. Blinded voice assessments showed improvement of USDRS scores post-DBS compared to pre-DBS, and with stimulator on compared to stimulator off. Discussion: We report the first three cases of SD responding favorably to bilateral VIM asleep DBS and summarize the nine cases so far of SD who have undergone thalamic DBS.

Orthostatic Tremor is Responsive to Bilateral Thalamic Deep Brain Stimulation: Report of Two Cases Performed Asleep.

Background: Orthostatic tremor (OT) is a hyperkinetic movement disorder characterized by rapid tremor in the lower extremities or trunk upon standing. Case Report: We report two patients presenting with OT, whose symptoms improved markedly following asleep bilateral thalamic deep brain stimulation (DBS) surgery. Discussion: Medically refractory OT can respond favorably to asleep bilateral DBS surgery similar to awake surgery, and may have the advantages of less psychological trauma to the patient, shorter procedure times, and less exposure to anesthesia.

Intraoperative test stimulation versus stereotactic accuracy as a surgical end point: a comparison of essential tremor outcomes after ventral intermediate nucleus deep brain stimulation.

OBJECTIVE Ventral intermediate nucleus deep brain stimulation (DBS) for essential tremor is traditionally performed with intraoperative test stimulation and conscious sedation, without general anesthesia (GA). Recently, the authors reported retrospective data on 17 patients undergoing DBS after induction of GA with standardized anatomical coordinates on T1-weighted MRI sequences used for indirect targeting. Here, they compare prospectively collected data from essential tremor patients undergoing DBS both with GA and without GA (non-GA). METHODS Clinical outcomes were prospectively collected at baseline and 3-month follow-up for patients undergoing DBS surgery performed by a single surgeon. Stereotactic, euclidean, and radial errors of lead placement were calculated. Functional (activities of daily living), quality of life (Quality of Life in Essential Tremor [QUEST] questionnaire), and tremor severity outcomes were compared between groups. RESULTS Fifty-six patients underwent surgery: 16 without GA (24 electrodes) and 40 with GA (66 electrodes). The mean baseline functional scores and QUEST summary indices were not different between groups (p = 0.91 and p = 0.59, respectively). Non-GA and GA groups did not differ significantly regarding mean postoperative percentages of functional improvement (non-GA, 47.9% vs GA, 48.1%; p = 0.96) or QUEST summary indices (non-GA, 79.9% vs GA, 74.8%; p = 0.50). Accuracy was comparable between groups (mean radial error 0.9 ± 0.3 mm for non-GA and 0.9 ± 0.4 mm for GA patients) (p = 0.75). The mean euclidean error was also similar between groups (non-GA, 1.1 ± 0.6 mm vs GA, 1.2 ± 0.5 mm; p = 0.92). No patient had an intraoperative complication, and the number of postoperative complications was not different between groups (non-GA, n = 1 vs GA, n = 10; p = 0.16). CONCLUSIONS DBS performed with the patient under GA to treat essential tremor is as safe and effective as traditional DBS surgery with intraoperative test stimulation while the patient is under conscious sedation without GA.

Parkinson's disease outcomes after intraoperative CT-guided "asleep" deep brain stimulation in the globus pallidus internus.

OBJECTIVE: Recent studies show that deep brain stimulation can be performed safely and accurately without microelectrode recording ortest stimulation but with the patient under general anesthesia. The procedure couples techniques for direct anatomical targeting on MRI with intraoperative imaging to verify stereotactic accuracy. However, few authors have examined the clinical outcomes of Parkinson's disease (PD) patients after this procedure. The purpose of this study was to evaluate PD outcomes following "asleep" deep brain stimulation in the globus pallidus internus (GPi). METHODS: The authors prospectively examined all consecutive patients with advanced PD who underwent bilateral GPi electrode placement while under general anesthesia. Intraoperative CT was used to assess lead placement accuracy. The primary outcome measure was the change in the off-medication Unified Parkinson's Disease Rating Scale motor score 6 months after surgery. Secondary outcomes included effects on the 39-Item Parkinson's Disease Questionnaire (PDQ-39) scores, on-medication motor scores, and levodopa equivalent daily dose. Lead locations, active contact sites, stimulation parameters, and adverse events were documented. RESULTS: Thirty-five patients (24 males, 11 females) had a mean age of 61 years at lead implantation. The mean radial error off plan was 0.8 mm. Mean coordinates for the active contact were 21.4 mm lateral, 4.7 mm anterior, and 0.4 mm superior to the midcommissural point. The mean off-medication motor score improved from 48.4 at baseline to 28.9 (40.3% improvement) at 6 months (p < 0.001). The PDQ-39 scores improved (50.3 vs 42.0; p = 0.03), and the levodopa equivalent daily dose was reduced (1207 vs 1035 mg; p = 0.004). There were no significant adverse events. CONCLUSIONS: Globus pallidus internus leads placed with the patient under general anesthesia by using direct anatomical targeting resulted in significantly improved outcomes as measured by the improvement in the off-medication motor score at 6 months after surgery.

Botulinum toxin therapy for cervical dystonia: the science of dosing.

The first-line treatment for cervical dystonia (CD) is botulinum toxin type A (BoNT-A), which has been established as a highly effective and well-tolerated therapy. However, this treatment is also complex and challenging to apply in clinical practice. Approximately 20% of patients discontinue therapy due to treatment failure, adverse effects, and other reasons. In addition, expert consensus recommendations are lacking to guide physicians in the optimal use of BoNT-A for CD. Among the issues still to be clarified is the optimal dosing frequency. The generally accepted standard for intervals between BoNT-A injections is ≥12 weeks; however, this standard is based primarily on the methodology of pivotal trials for the BoNT-A products, rather than on evidence that it is optimal in comparison to other intervals. While some retrospective, observational studies of BoNT-A used in clinical practice appear to support the use of ≥12-week dosing intervals, it is often unclear in these studies how the need for reinjection was determined. In contrast, a prospective dose-ranging trial in which patients were allowed to request reinjection as early as 8 weeks showed that about half of patients receiving abobotulinumtoxinA, at the currently recommended initial dose of 500 U, requested reinjection at 8 weeks. Moreover, results from an open-label, 68-week extension phase of the pivotal trial of incobotulinumtoxinA showed that 47.1% of patients had received reinjection at ≤12 weeks. Ongoing studies, such as the Cervical Dystonia Patient Registry for Observation of BOTOX® Efficacy (CD PROBE), may help clarify this question of optimal dosing intervals for BoNT-A in CD.

IncobotulinumtoxinA (Xeomin®) injected for blepharospasm or cervical dystonia according to patient needs is well tolerated.

Typically, botulinum toxin injections for blepharospasm or cervical dystonia (CD) are administered at approximately 3-month intervals, reflecting concerns that shorter intervals might increase the risk of adverse events (AEs) and development of neutralizing antibodies. These post-hoc analyses investigated flexible incobotulinumtoxinA (Xeomin®) injection intervals (6-20 weeks) in patients with blepharospasm or CD. Patients received up to 6 injections at intervals ≥ 6 weeks, as determined by physician assessment upon patient request. The blepharospasm study permitted flexible doses (≤ 50 U/eye). The CD study employed fixed dosing using incobotulinumtoxinA 120 U, 240 U, or placebo for the first treatment followed by subsequent randomization to 120 U or 240 U for the extension period. Standard safety assessments were performed. Intervals <12 weeks were employed in 207 of 461 (44.9%) treatment cycles for blepharospasm and in 369 of 821 (44.9%) treatment cycles for CD. The most frequent AEs were eyelid ptosis and dry eyes in patients treated for blepharospasm, and dysphagia and neck pain in patients with CD. AE frequency and severity were similar for intervals <12 weeks and ≥ 12 weeks in both studies. In conclusion, repeated incobotulinumtoxinA injections employing flexible intervals (6-20 weeks) per patients' needs were well tolerated. No additional safety concerns were observed with <12-week intervals compared with ≥ 12-week intervals.

A randomized, double-blind study of repeated incobotulinumtoxinA (Xeomin(®)) in cervical dystonia.

IncobotulinumtoxinA (Xeomin(®), NT 201), a preparation without accessory (complexing) proteins, has shown comparable efficacy and safety to onabotulinumtoxinA in treating cervical dystonia (CD). This study evaluated the efficacy and safety of repeated incobotulinumtoxinA injections in subjects with CD. Following a ≤20-week placebo-controlled, randomized, double-blind, single-dose main period, subjects could enter a ≤68-week prospective, randomized, double-blind, repeated-dose, flexible-interval (minimum 6 weeks) extension period with 240 U or 120 U of incobotulinumtoxinA (≤5 injections). Outcome measures included the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and adverse events (AEs). Of 219 subjects completing the main period, 214 were randomized in the extension period to receive incobotulinumtoxinA 240 U (n = 111) or 120 U (n = 103); 169 subjects completed the extension period, with 90 receiving five injection sessions. Both doses of incobotulinumtoxinA provided statistically significant and clinically relevant improvements in mean TWSTRS-Total, -Severity, -Disability, and -Pain scores, from each injection session to respective 4-week follow-up visits. The most frequently reported AE was dysphagia (240 U: 23.4 %; 120 U: 12.6 %), which did not result in any study withdrawals. There was no impact of injection interval on the incidence of AEs (post hoc analysis). A major limitation of this study was the fixed dose design requested by regulatory authorities, which does not reflect clinical practice. However, repeated incobotulinumtoxinA injections (240 or 120 U; flexible intervals) provided sustained efficacy and were well tolerated, with no unexpected safety risks following repeated injections. The incidence of AEs was similar in subjects requiring repeated injections at shorter intervals (≤12 weeks) compared with those treated using longer intervals (>12 weeks).

Efficacy and Safety of IncobotulinumtoxinA in Subjects Previously Treated with Botulinum Toxin Versus Toxin-Naïve Subjects with Cervical Dystonia.

BACKGROUND: To determine whether botulinum toxin treatment history affected the outcomes of a study comparing the safety and efficacy of incobotulinumtoxinA with placebo in subjects with cervical dystonia (CD). METHODS: This was a prospective, double-blind, randomized, placebo-controlled, multicenter trial in botulinum toxin-treated or toxin-naïve CD subjects. Subjects received a fixed dose of either 120 U or 240 U of incobotulinumtoxinA or placebo. The primary outcome measure was change from baseline to Week 4 in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score. Treatment-emergent adverse events (TEAEs) were also evaluated. This report represents a subgroup analysis of botulinum toxin-treated or toxin-naïve subjects. RESULTS: Participants (N = 233; 38.6% toxin-naïve) had a mean age of 52.8 years. IncobotulinumtoxinA significantly improved TWSTRS total scores from baseline to Week 4 in both dose groups versus placebo, and the improvement persisted through the end of the study (≤20 weeks). Both the previously toxin-treated and toxin-naïve subjects demonstrated significant improvements in TWSTRS total scores at Week 4 compared to baseline. The most frequent TEAEs in the incobotulinumtoxinA groups were dysphagia, neck pain, and muscular weakness, which were generally mild. TEAEs were more common in the 240 U group and toxin-naïve subjects. DISCUSSION: Overall, incobotulinumtoxinA was safe and effective in CD, regardless of toxin therapy history. A lower starting dose may be better tolerated among toxin-naïve subjects without sacrificing efficacy.

Bilateral globus pallidus internus deep brain stimulation in Parkinson's disease with periodic limb movement disorder.

Deep brain stimulation for Parkinson's disease is a well-established therapeutic intervention for refractory disease. The main nuclear targets are the subthalamic nucleus and the globus pallidus internus. Periodic limb movements are often an associated condition in patients with Parkinson's disease. Both conditions can respond to dopaminergic agents. The case of a 57-year-old man with severe Parkinson's disease and periodic limb movement who underwent bilateral globus pallidus deep brain stimulation surgery for his Parkinson's disease is presented and discussed. Intraoperatively the patient's periodic limb movements responded to voltage stimulation higher than those required for improvement of his parkinsonian symptoms. The immediate and reversible improvement in these symptoms contralateral to the stimulation site suggests pallidal stimulation may directly ameliorate periodic limb movement symptoms.

Primary writing tremor responds to unilateral thalamic deep brain stimulation.

Primary writing tremor is a task associated tremor which occurs during and interferes with handwriting. Considered in most cases to be a nonprogressive disorder, a number of patients are significantly debilitated by the disease. The pathophysiology of the disorder is not fully understood, but felt to represent a variant of either essential tremor or dystonia versus a separate entity. Treatment has been limited to medications, writing devices and botulinum toxin type A for most patients. Recently, deep brain stimulation has been reported in a few patients as an effective option for those patients with medically refractory symptoms. We report our experience in a patient with primary writing tremor who underwent successful thalamic deep brain stimulation, discuss the current theories on the pathophysiology of the disorder and review the current literature of deep brain stimulation for refractory primary writing tremor.

Long-term benefit of bilateral subthalamic deep brain stimulation on camptocormia in Parkinson's disease.

We report the case of a 63-year-old female with a long history of severe Parkinson's disease (PD) and subsequent onset of debilitating camptocormia who underwent successful bilateral subthalamic nucleus deep brain stimulation surgery (STN DBS). The literature and previous reports are reviewed. The patient history and details of the surgical procedure are reported including the implantable pulse generator (IPG) settings and response to stimulation. The results of her PD symptom and camptocormia improvements are discussed. Five year postoperatively, the patient has enjoyed good results for both her PD symptoms as well as significant and sustained improvement in her thoracolumbar flexion deformity. She remains on minimal medications and no longer requires any assistive devices for ambulation. Comparison and contrast of the current world literature on DBS for camptocormia is reviewed. We discuss the current targets used for DBS in the setting of camptocormia in the cases reported, both PD associated and not associated. The optimal target has yet to be defined and further work on appropriate patient selection is needed.

Autonomic function, as self-reported on the SCOPA-autonomic questionnaire, is normal in essential tremor but not in Parkinson's disease.

OBJECTIVE: To compare autonomic function of subjects with Parkinson's disease (PD) and essential tremor (ET) relative to controls. BACKGROUND: It has been reported that patients with PD have autonomic dysfunction while no literature exists regarding autonomic function in ET. METHODS: Subjects with PD, ET, and controls had autonomic function measured using the SCOPA-Autonomic questionnaire, with the total and domain scores transformed to a scale of 0-100 points. RESULTS: 62 subjects with PD, 84 with ET, and 291 controls were included. Women were more prevalent in control (69%) compared to PD (44%) and ET (44%) groups, and mean age was significantly younger in PD (73 yrs) and older in ET (83) compared to controls (81). The mean SCOPA-Aut Total score in PD was significantly higher than controls, with no difference in ET. No autonomic dysfunction was found in any domain in ET but in PD there were significant abnormalities in gastrointestinal, cardiovascular, urinary, and thermoregulatory domains. Individual question data revealed a significantly higher percentage of subjects with dysfunction on 11/23 questions in the PD group but only 1 question (sialorrhea) in the ET group compared with controls. CONCLUSION: Autonomic scores, particularly gastrointestinal, cardiovascular, urinary, and thermoregulatory were increased in patients with PD, as assessed by SCOPA-Aut. Patients with ET did not exhibit autonomic dysfunction, with the exception of sialorrhea.