There is growing evidence that differences exist in the gut microbiota of patients with Parkinson’s Disease (PD) compared with health controls, and so treatment with Faecal Microbiota Transplantation (FMT) may provide a novel approach towards altering disease progression and response to treatment. We performed a pilot study looking at the safety and tolerability of FMT, its effect on the microbiome, and improvement of symptoms in PD. This was an open label study wherein 12 patients with mild to moderate PD were administered FMT via enema for 6 months. The primary objectives were safety and tolerability of therapy as well as changes in motor and non-motor symptoms of PD. FMT administered as liquid enema was safe and well tolerated, associated with mild and self-resolving gastrointestinal symptoms. We found no significant change in motor outcomes post FMT however showed a trend towards improvement in daily OFF time after 2 months of treatment. We found no significant improvement in non-motor symptoms of PD after 6-months of FMT, however showed improvement in quality of life and non-motor symptom scores at 2 months as well as a trend towards improvement in parts 1 and 2 of the MDS-UPDRS. All improvements regressed back to baseline after 6 months of treatment. The administration of FMT over an extended 6-month period for the treatment of mild to moderate PD is safe and tolerable. FMT was associated with a transient reduction in daily motor OFF time as well as multiple self-reported non-motor symptoms.

Emerging evidence suggests gut microbiota differences in Parkinson's Disease (PD) may impact disease progression and treatment. Faecal Microbiota Transplantation (FMT) offers a potential therapeutic approach. We conducted an open-label pilot study to assess the safety, tolerability, and symptom impact of FMT in 12 patients with mild to moderate PD, administered via enema for 6 months. FMT was safe and well tolerated, causing only mild, transient gastrointestinal symptoms. While no significant motor symptom changes were observed, there was a trend toward reduced daily OFF time at 2 months. Whilst no sustained improvement in non-motor symptoms was found after 6 months, transient improvements in quality of life and non-motor scores were noted at 2 months; these gains regressed by study end. Overall, extended FMT therapy in PD appears safe and tolerable, with reduction in daily motor OFF time and self-reported non-motor symptoms that was not sustained throughout the 6-months of treatment.

Convexity subarachnoid haemorrhage (SAH) has many possible causes. A 76-year-old man presented with back pain, left leg weakness, and hypertension. His brain imaging showed convexity SAH, with additional intraventricular blood and extensive spinal SAH from T3-S2. Following deterioration from a probable further haemorrhage, with development of left foot myoclonus, a spinal digital subtraction angiogram was normal but cerebral angiogram identified a cerebral dural arteriovenous fistula, which was successfully embolised. Convexity SAH has a heterogeneous clinical presentation and dural arteriovenous fistula is a potential cause.

To compare the efficacy of subcutaneous foslevodopa/foscarbidopa (LDP/CDP) with oral levodopa/carbidopa (LD/CD) across prespecified subgroups of patients with advanced Parkinson's disease (PD) in a phase 3 study.

Objectives There are no disease-modifying treatments that arrest or reverse tau hyperphosphorylation in tauopathies. Through its action in upregulating protein phosphatase 2 (PP2A), sodium selenate has been shown to reduce levels of total-tau, phosphorylated-tau and hyperphosphorylated-tau in animal models of disease associated with increases in tau as well as early phase clinical trials. This study is a placebo-controlled, randomised controlled trial of sodium selenate as a treatment for the primary tauopathy, progressive supranuclear palsy (PSP). Methods 70 patients with probable PSP (Richardson's syndrome) will be recruited, and randomised to treatment with sodium selenate (15 mg tds) or placebo (1:1) over 52 weeks. The study is recruiting at 6 sites across Australia. The primary study outcome will be change in MRI volume composite (frontal lobe+midbrain-3rd ventricle) over 52 weeks of treatment. Secondary outcome measures will include change on the PSP rating scale, clinical global impression of change, and change in midbrain mean diffusivity. Results Presently, 19 patients have been screened, resulting in 3 screen fails, 15 randomisations and 1 awaiting randomisation. Of the 15 patients randomised, 3 have completed the study, 1 withdrew early (due to an adverse event) and 11 remain on treatment. Baseline characteristics of randomised patients are: Age median 64 years (range 47–74), male (n=10) and PSPRS total score: mean 37.4 (range 11–61). To date safety has been good with no serious adverse events related to treatment. Conclusion Recruitment is ongoing and is expected to complete in March 2024, with last patient last visit in June 2025.

Objective: To characterize the time course of adverse events (AEs) in patients with Parkinson's disease (PD) and motor fluctuation treated with foslevodopa/foscarbidopa. Background: Continuous subcutaneous infusion with foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs, provides individualized, 24-hour/day therapy. Design/Methods: Patients aged ≥30 years with idiopathic, LD-responsive PD inadequately controlled with current therapy (≥2.5 average "Off" hours/day) were enrolled in a 12-week, phase 3, randomized, double-blind study comparing foslevodopa/foscarbidopa to oral immediate release LD/CD (NCT04380142). Foslevodopa/foscarbidopa doses were titrated and individualized during the 4-week optimization period, followed by a stable dose regimen during the 8-week maintenance period. Safety was assessed in all patients who received ≥1 dose of study drug. Results: A total of 74 patients received foslevodopa/foscarbidopa. Overall AEs occurred more frequently during the 4-week optimization vs the 8-week maintenance period (74.3% vs 67.9%), as did treatment discontinuations due to AEs (16.2% vs 7.1%). A greater proportion of patients experienced movement-related AEs during optimization vs maintenance, including dyskinesia (10.8% vs 0%), "On" and "Off" phenomenon (6.8% vs 1.8%), and falls (13.5% vs 8.9%). Incidence of infusion site AEs was higher during optimization vs maintenance (67.6% vs 58.9%); individual infusion site AEs generally followed a similar trend (erythema [20.3% vs 21.4%], pain [21.6% vs 8.9%], cellulitis [10.8% vs 12.5%], bruising [6.8% vs 1.8%], nodules [5.4% vs 3.6%]). Conclusions: In this phase 3 trial involving patients with PD treated with foslevodopa/foscarbidopa, AEs and discontinuations were generally higher during the 4-week optimization compared with the 8-week maintenance period. Higher rates of AEs and discontinuations during optimization may have been the result of the dose titration process and acclimation to a new drug delivery system. Patient and physician training, education, and expectation setting before treatment initiation and during optimization may help reduce rates of treatment discontinuation. Disclosure: Dr. Kern has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. The institution of Dr. Kern has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Scientific. The institution of Dr. Kern has received research support from Boston Scientific. The institution of Dr. Kern has received research support from AbbVie Pharmaceticals. Dr. Kern has received research support from Medtronic. Dr. Dashtipour has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Amneal, Abbvie, Acorda, Acadia, Ipsen, Supernus, Sunovion, Neurocrine, Teva. Dr. Dashtipour has received personal compensation in the range of $100,000-$499,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amneal, Abbvie, Acadia, Supernus. Dr. Dashtipour has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Amneal, Acorda, Abbvie, Ipsen, Teva, Neurocrine, SupernusPD, sunovion . Dr. Aldred has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Medtronic. Dr. Aldred has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Boston Scientific. Dr. Aldred has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Abbvie. Dr. Aldred has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen . Dr. Aldred has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan . Dr. Aldred has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quadralynx. Dr. Aldred has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Aldred has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific. Dr. Aldred has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic. Dr. Aldred has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Abbvie. Dr. Aldred has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda. Dr. Aldred has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Adamas. Dr. Aldred has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Allergan. Dr. Aldred has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Boston Scientific. Dr. Aldred has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for TEVA. Dr. Aldred has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Medtronic. Dr. Aldred has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for US World Meds. Dr. Aldred has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Aldred has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sunovion. Dr. Aldred has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amneal. Dr. Aldred has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Aldred has received personal compensation in the range of $100,000-$499,999 for serving as an Expert Witness for Arete Neuroscience, PLLC. The institution of Dr. Aldred has received research support from Biogen . The institution of Dr. Aldred has received research support from Abbvie. The institution of Dr. Aldred has received research support from Atara. The institution of Dr. Aldred has received research support from Takeda. The institution of Dr. Aldred has received research support from Merz. The institution of Dr. Aldred has received research support from AstraZeneca. The institution of Dr. Aldred has received research support from Neurocrine. The institution of Dr. Aldred has received research support from Aptinyx. The institution of Dr. Aldred has received research support from Cerevance. The institution of Dr. Aldred has received research support from Boston Scientific . The institution of Dr. Aldred has received research support from Parkinson Foundation . The institution of Dr. Aldred has received research support from Roche. The institution of Dr. Aldred has received research support from Theravance. The institution of Dr. Aldred has received research support from Triplet Therapeutics. The institution of Dr. Aldred has received research support from UCB. The institution of Dr. Aldred has received research support from Cerevel . The institution of Dr. Aldred has received research support from Sage Therapeutics. The institution of Dr. Aldred has received research support from Annovis. The institution of Dr. Aldred has received research support from Biovie. The institution of Dr. Aldred has received research support from Athira. The institution of Dr. Aldred has received research support from IRL. The institution of Dr. Aldred has received research support from NeuroDerm. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Seqiris. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Seqiris. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Seqiris. Robert Iansek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie Pharmaceuticals. Dr. Kukreja has received personal compensation for serving as an employee of AbbVie. Dr. Kukreja has stock in AbbVie. Lars Bergmann has received personal compensation for serving as an employee of Abbvie. Lars Bergmann has stock in Abbvie. Nahome Fisseha has received personal compensation for serving as an employee of AbbVie. Nahome Fisseha has received stock or an ownership interest from AbbVie. Dr. Gupta has nothing to disclose. Dr. Talapala has nothing to disclose. Dr. Jeong has received personal compensation for serving as an employee of AbbVie. An immediate family member of Dr. Jeong has received personal compensation in the range of $500,000-$999,999 for serving as a Consultant for Stryker. Dr. Jeong has stock in AbbVie. Dr. Fung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Fung has received publishing royalties from a publication relating to health care. Dr. Lepetit has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Therapanacea.

Objective: The aim of this analysis was to characterize the patient populations of two pivotal clinical trials with foslevodopa/foscarbidopa (LDP/CDP, also referred to as ABBV-951), an investigational drug for Parkinson's Disease (PD). Background: While identification of advanced PD (aPD) continues to be a challenge, new tools have emerged to help clinicians determine if patients have reached aPD. Recently, a validated tool known as MANAGE-PD was launched to help clinicians identify suboptimal PD symptom control and categorize patients with advancing PD as either controlled, inadequately controlled possibly needing treatment optimization, or potentially eligible for device-aided therapies (DATs). Design/Methods: This post-hoc analysis evaluated the baseline characteristics of patients enrolled in two ABBV-951 phase 3 studies (one double-blind/double-dummy, NCT04380142; and one open-label safety, NCT03781167). Additionally, in the open-label study, the MANAGE-PD criteria (section 1 and 2) was applied to the participants prospectively, which may further validate the use of the tool in identifying patients eligible for DATs. Results: In the double-blind (n=141) and open-label (n=244) studies, the percentages of participants at baseline in the 55–74 age category were 66.7% and 73.4%, that had daily off time >3 hours were 97.2% and 88.1%, that had a 0–3 Hoehn and Yahr stage were 96.5% and 94.7%, and had time to occurrence of motor fluctuations as >3 years of 73.0% and 77.5%, respectively. Based on the MANAGE-PD categorization, in the open label-study all patients were considered to be inadequately controlled with the current treatment regimen, with 14.8% possibly benefitting from current treatment optimization, and 85.2% as potentially benefitting from DAT. Conclusions: The vast majority of patients from the pivotal trials in the LDP/CDP clinical program were consistent with populations characterized as 'advanced' and eligible for a DAT such as ABBV-951, which was substantiated using the MANAGE-PD categorization, adding to the validation of this tool. Disclosure: Per Odin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Per Odin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AbbVie. Per Odin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lobsor. Per Odin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AbbVie. Per Odin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Britannia. Per Odin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Per Odin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Nordic Infucare. Per Odin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zambon. Per Odin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bial. The institution of Per Odin has received research support from AbbVie. The institution of Per Odin has received research support from Parkinsonfonden. The institution of Per Odin has received research support from Swedish Research Council. The institution of Per Odin has received research support from Region Skåne. Per Odin has received publishing royalties from a publication relating to health care. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbott. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AbbVie. Dr. Pahwa has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for ACADIA. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acorda. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amneal. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Cala Health. Dr. Pahwa has received personal compensation in the range of $0-$499 for serving as a Consultant for Global Kinetics. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kyowa. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sunovion. Dr. Pahwa has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Supernus. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allevion. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avion. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Insightec. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jaaz. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neuroderm. Dr. Pahwa has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Photopharmics. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage. Dr. Pahwa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Wren. The institution of Dr. Pahwa has received research support from Abbott. The institution of Dr. Pahwa has received research support from Abbvie. The institution of Dr. Pahwa has received research support from Biogen. The institution of Dr. Pahwa has received research support from Biohaven. The institution of Dr. Pahwa has received research support from Boston Scientific. The institution of Dr. Pahwa has received research support from EIP. The institution of Dr. Pahwa has received research support from Global Kinetics. The institution of Dr. Pahwa has received research support from Amneal. The institution of Dr. Pahwa has received research support from Neuraly. The institution of Dr. Pahwa has received research support from Parkinson Foundation. The institution of Dr. Pahwa has received research support from Pharma 2B. The institution of Dr. Pahwa has received research support from Roche. The institution of Dr. Pahwa has received research support from Sage. The institution of Dr. Pahwa has received research support from Sun Pharma. The institution of Dr. Pahwa has received research support from Theranexus. The institution of Dr. Pahwa has received research support from Theravance. The institution of Dr. Pahwa has received research support from Voyager. The institution of Dr. Pahwa has received research support from Neuroderm. Dr. Farmer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Teva. Dr. Farmer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for USWorldMeds. Dr. Farmer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for KyowaKirin. Dr. Farmer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Acadia. Dr. Farmer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Abbvie. Dr. Farmer has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Live. The institution of Dr. Farmer has received research support from Parkinson's Foundation. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Seqiris. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Seqiris. Dr. Kimber has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Seqiris. Dr. Bergmans has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan. Dr. Bergmans has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Bergmans has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merz. Dr. Bergmans has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zambon. Dr. Freire Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Freire Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zambon. Dr. Freire Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Freire Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zambon. Dr. Freire Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB pharma. Dr. Freire Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bial. Dr. Freire Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. Dr. Freire Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Prof. Ray Chaudhuri has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Advisory board recent: AbbVie, UCB, GKC, Bial, Cynapsus, Lobsor, Stada, Zambon, Profile Pharma, Synovion, Roche, Therevance, Scion, Britannia, Acadia, 4D Pharma. Prof. Ray Chaudhuri has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AbbVie, Britannia, UCB, Zambon, Novartis, Boeringer Ingelheim, Bial, Kyowa Kirin, SK Pharma . Prof. Ray Chaudhuri has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for GMC. The institution of Prof. Ray Chaudhuri has received research support from EU Horizon 2020, Parkinson's UK, NIHR, Parkinson's Foundation, Wellcome Trust Aacdemic grants over 2 years ago: Kirby Laing Foundation, MRC. Prof. Ray Chaudhuri has received publishing royalties from a publication relating to health care. Dr. Gupta has nothing to disclose. Dr. Yan has nothing to disclose. Lars Bergmann has received personal compensation for serving as an employee of Abbvie. Lars Bergmann has stock in Abbvie. Dr. Kukreja has received personal compensation for serving as an employee of AbbVie. Dr. Kukreja has stock in AbbVie. Dr. Antonini has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BIAL. Dr. Antonini has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ABBVIE. Dr. Antonini has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Antonini has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for THERAVANCE. Dr. Antonini has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ROCHE. Dr. Antonini has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ABBVIE. Dr. Antonini has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ZAMBON. Dr. Antonini has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BOEHRINGER.

Introduction Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinson’s disease (PD), is administered as a 24-hour/day continuous subcutaneous infusion (CSCI) with a single infusion site. The efficacy and safety of foslevodopa/foscarbidopa versus oral immediate-release LD/CD was previously demonstrated in patients with PD in a 12-week, randomized, double-blind, phase 3 trial (NCT04380142). We report the results of a separate 52-week, open-label, phase 3 registrational trial (NCT03781167) that evaluated the safety/tolerability and efficacy of 24-hour/day foslevodopa/foscarbidopa CSCI in patients with advanced PD. Methods Male and female patients with levodopa-responsive PD and ≥ 2.5 hours of “Off” time/day received 24-hour/day foslevodopa/foscarbidopa CSCI at individually optimized therapeutic doses (approximately 700–4250 mg of LD per 24 hours) for 52 weeks. The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in normalized “Off” and “On” time, percentage of patients reporting morning akinesia, Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Parkinson’s Disease Sleep Scale–2 (PDSS-2), 39-item Parkinson’s Disease Questionnaire (PDQ-39), and EuroQol 5-dimension questionnaire (EQ-5D-5L). Results Of 244 enrolled patients, 107 discontinued, and 137 completed treatment. Infusion site events were the most common adverse events (AEs). AEs were mostly nonserious (25.8% of patients reported serious AEs) and mild/moderate in severity. At week 52, “On” time without troublesome dyskinesia and “Off” time were improved from baseline (mean [standard deviation (SD)] change in normalized “On” time without troublesome dyskinesia, 3.8 [3.3] hours; normalized “Off” time, −3.5 [3.1] hours). The percentage of patients experiencing morning akinesia dropped from 77.7% at baseline to 27.8% at week 52. Sleep quality (PDSS-2) and quality of life (PDQ-39 and EQ-5D-5L) also improved. Conclusion Foslevodopa/foscarbidopa has the potential to provide a safe and efficacious, individualized, 24-hour/day, nonsurgical alternative for patients with PD. Trial Registration Number ClinicalTrials.gov identifier NCT03781167.

Background Levodopa is the most effective symptomatic therapy for Parkinson's disease, but patients with advanced Parkinson's disease develop motor fluctuations with chronic oral levodopa therapy. Foslevodopa-foscarbidopa is a soluble formulation of levodopa and carbidopa prodrugs that is delivered as a 24-h/day continuous subcutaneous infusion, and we aimed to assess the safety and efficacy of this formulation in patients with advanced Parkinson's disease. Methods A 12-week randomised, double-blind, double-dummy, active-controlled study was done at 65 academic and community study centres in the USA and Australia. Patients with levodopa-responsive advanced Parkinson's disease inadequately controlled on current therapy, including at least 2.5 h of average daily off time, were randomly assigned (1:1) to continuous subcutaneous infusion of foslevodopa-foscarbidopa plus oral placebo or to oral immediate-release levodopa-carbidopa plus continuous subcutaneous infusion of placebo solution. Randomisation was stratified by site by means of a permutated-block schedule with a block size of two. The participants, treating investigators, study site personnel, and sponsor were masked to treatment group allocation. The primary and first key secondary endpoint in the hierarchical testing strategy were change from baseline to week 12 in on time without troublesome dyskinesia and off time, respectively; both endpoints were evaluated by an intention-to-treat analysis applying a mixed model for repeated measures analysis. Safety and tolerability were assessed throughout the study. The study is completed and is listed on ClinicalTrials.gov, NCT04380142. Findings Between Oct 19, 2020, and Sept 29, 2021, of 270 participants screened and 174 enrolled, 141 were randomly assigned and received continuous subcutaneous infusion of foslevodopa-foscarbidopa plus oral placebo capsules (n=74) or oral encapsulated immediate-release levodopa-carbidopa plus continuous subcutaneous infusion of placebo solution (n=67). Compared with levodopa-carbidopa, foslevodopa-foscarbidopa showed a significantly greater increase in on time without troublesome dyskinesia (model-based mean [SE] 2.72 [0.52] vs 0.97 [0.50] h; difference 1.75 h, 95% CI 0.46 to 3.05; p=0.0083) and a significantly greater reduction in off time (-2.75 [0.50] vs -0.96 [0.49] h; difference -1.79 h, -3.03 to -0.54; p=0.0054). Hierarchical testing ended after the first secondary endpoint. Adverse events were reported in 63 (85%) of 74 patients in the foslevodopa-foscarbidopa group versus 42 (63%) of 67 in the levodopa-carbidopa group, and incidences of serious adverse events were similar between the groups (six [8%] of 74 vs four [6%] of 67, respectively). The most frequent adverse events in the foslevodopa-foscarbidopa group were infusion site adverse events (erythema 20 [27%]), pain 19 [26%]), cellulitis (14 [19%]), and oedema (nine [12%]), most of which were non-serious and mild-moderate in severity. The only system organ class that had more than one serious adverse event in the foslevodopa-foscarbidopa group was infections and infestations (catheter site cellulitis [one [1%]] and infusion site cellulitis [one [1%]). Adverse events led to premature discontinuation of study drug in 16 (22%) of 74 participants in the foslevodopa-foscarbidopa group versus one (1%) of 67 participants in the oral levodopa-carbidopa group. Interpretation Foslevodopa-foscarbidopa improved motor fluctuations, with benefits in both on time without troublesome dyskinesia and off time. Foslevodopa-foscarbidopa has a favourable benefit-risk profile and represents a potential non-surgical alternative for patients with advanced Parkinson's disease. Copyright (C) 2022 Published by Elsevier Ltd. All rights reserved.

BackgroundThere are currently no Australian guidelines to assist clinicians performing deep brain stimulation (DBS) procedures in setting postoperative driving restrictions.PurposeWe aimed to provide recommendations for post-DBS driving restrictions to guide practice in Australia.MethodsA review of current Australian and international driving guidelines, literature regarding the adverse effects of DBS and literature regarding the long-term effect of neurostimulation on driving was conducted using Elton B Stephens Company discovery service-linked databases. Australian neurologists and neurosurgeons who perform DBS were surveyed to gain insight into existing practice.ResultsNo guidance on driving restrictions following DBS surgery was found, either in existing driving guidelines or in the literature. There was a wide difference seen in the rates of reported adverse effects from DBS surgery. The most serious adverse events (haemorrhage, seizure and neurological dysfunction) were uncommon. Longer term, there does not appear to be any adverse effect of DBS on driving ability. Survey of Australian practitioners revealed a universal acceptance of the need for and use of driving restrictions after DBS but significant heterogeneity in how return to driving is managed.ConclusionWe propose a 6-week driving restriction for private licences and 6-month driving restriction for commercial licences in uncomplicated DBS. We also highlight some of the potential pitfalls and pearls to assist clinicians to modify these recommendations where needed. Ultimately, we hope this will stimulate further examination of this issue in research and by regulatory bodies to provide more robust direction for practitioners performing DBS implantation.