Publications by authors named "Neal Hermanowicz"

31 Publications

Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase-Associated Neurodegeneration.

Mov Disord 2021 06 16;36(6):1342-1352. Epub 2020 Nov 16.

Research and Development, Retrophin, Inc., San Diego, California, USA.

Background: Pantothenate kinase-associated neurodegeneration (PKAN) currently has no approved treatments.

Objectives: The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression.

Methods: This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Patients with pathogenic variants of PANK2, aged 6 to 65 years, with a score ≥6 on the PKAN-Activities of Daily Living (PKAN-ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN-ADL.

Results: Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN-related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN-ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was -0.09 (-1.69 to 1.51; P = 0.9115). The overall incidence of treatment-emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups.

Conclusions: Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN-ADL in patients with PKAN. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246547PMC
June 2021

Assessing and addressing footwear needs in Parkinson's disease-design thinking in neurology.

NeuroRehabilitation 2019 Dec;45(4):443-448

UC Irvine Department of Neurology, Irvine, CA, USA.

Background: Parkinson's disease (PD) is a neurodegenerative movement disorder that results in a variety of motor deficits such as unsteady gait, bradykinesia, resting tremor, and rigidity.

Objective: The objective of this study was to quantify and assess the challenges and preferences Parkinson's disease patients have regarding footwear.

Methods: A 13-question survey was designed to assess footwear challenges and preferences among PD patients. A total of 89 PD patients, both male and female, were surveyed in the outpatient setting at UC Irvine during their appointments with the senior author.

Results: A majority of the PD patients in our cohort (64%) reported experiencing difficulties wearing shoes on their own. Patients who experienced difficulties wearing shoes were significantly more likely to report having been forced to make changes to their desired outfits (p = 0.0011), choosing not to wear dress shoes due to their discomfort (p = 0.0175), and preferring shoes without laces (p = 0.0 048).

Conclusions: The present study is the first attempt to use a survey to quantify the challenges and preferences reported by PD patients in regard to their usage of footwear. Inspired by our findings, the study team designed a novel dress shoe prototype that may address some of the difficulties and concerns gathered through our survey.
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http://dx.doi.org/10.3233/NRE-192897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029357PMC
December 2019

PKG Movement Recording System Use Shows Promise in Routine Clinical Care of Patients With Parkinson's Disease.

Front Neurol 2019 1;10:1027. Epub 2019 Oct 1.

Department of Neurology, University of California, Irvine, Irvine, CA, United States.

Parkinson's disease (PD) is a debilitating, neurodegenerative disorder that affects nearly one million people. It's hallmark signs and symptoms include slow movements, rigidity, tremor, and unstable posture. Additionally, non-motor symptoms such as sleeplessness, depression, cognitive impairment, impulse control behaviors (ICB) have been reported. Today, treatment regimens to modify disease progression do not exist and as such, treatment is focused on symptom relief. Additionally, physicians are challenged to base their diagnoses and treatment plans on unreliable self-reported symptoms, even when used in conjunction to validated assessments such as the Unified Parkinson's Disease Rating Scale (UPDRS) and clinical exams. Wearable technology may provide clinicians objective measures of motor problems to supplement current subjective methods. Global Kinetics Corporation (GKC) has developed a watch-device called the Personal KinetiGraph (PKG) that records movements and provides patients medication dosing reminders. A separate clinician-use report supplies longitudinal motor and event data. The PKG was FDA-cleared in September 2016. We studied 63 PD patients during 85 routine care visits in 2 US academic institutions, evaluating the clinical utility of the PKG. Patients wore a PKG for 6 continuous days before their visit. Next, PKG data was uploaded to produce a report. In clinic, physicians discussed PD symptoms with patients and conducted a motor examination prior to reviewing the PKG report and comparing it to their initial assessments. Lastly, patient, caregiver and physician satisfaction surveys were conducted by each user. Across all visits when patients did not report bradykinesia or dyskinesia, the PKG reported these symptoms (50 and 33% of the time, respectively). The PKG provided insights for treatment plans in 50 (79%) patients across 71 (84%) visits. Physicians found improved patient dialogue in 50 (59%) visits, improved ability to assess treatment impact in 32 (38%) visits, and improved motor assessment in 28 (33%) visits. Patients stated in 82% of responses that they agreed or strongly agreed in PKG training, usability, performance, and satisfaction. In 39% of responses, they also reported a very valuable impact on their care. PKG use in 63 PD patients within our clinical practice showed clinically relevant utility in many areas.
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http://dx.doi.org/10.3389/fneur.2019.01027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779790PMC
October 2019

Two-year clinical outcomes associated with robotic-assisted subthalamic lead implantation in patients with Parkinson's disease.

J Robot Surg 2020 Aug 13;14(4):559-565. Epub 2019 Sep 13.

Department of Neurosurgery, University of California, 200 S. Manchester Avenue, Suite 210, Irvine, Orange, CA, 92868, USA.

Few centers have routinely implemented robotic stereotactic systems for deep brain stimulator (DBS) placement. The present study compares clinical outcomes associated with robotic-assisted subthalamic nucleus (STN)-targeted DBS surgery in patients with Parkinson's disease (PD) to those of the traditional frame-based method. A retrospective chart review was performed (February 2013-June 2017). Thirty-three patients were implanted using the Cosman-Roberts-Wells (CRW) frame and 27 patients were implanted using the ROSA robot. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) or UPDRS part III motor scores and levodopa equivalent daily doses (LEDD) were examined preoperatively and at 6, 12, and 24 months of follow-up. Operative times and complication rates were recorded. For the frame-based group, the reduction in the mean MDS-UPDRS part III motor score compared to baseline was 27% both at 6 and 12 months, and 36.7% at 24 months. For the robotic-assisted group, the reduction in the mean motor score from baseline was 17.6% at 6 months, 19% at 12 months and 21.4% at 24 months. The mean LEDD for the frame-based group decreased by 48.7% at 6 months, 56.7% at 12 months, and 29.7% at 24 months. For the robotic-assisted group, the mean LEDD decreased by 42% at 6 months, 45% at 12 months and 50% at 24 months. There were no significant differences in the mean motor scores and the LEDD reduction between the two groups. Operative times tended to be longer for robotic-assisted DBS surgery. Clinical outcomes associated with robotic-assisted surgery are comparable to those with frame-based surgery.
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http://dx.doi.org/10.1007/s11701-019-01025-xDOI Listing
August 2020

Impact of non-motor symptoms in Parkinson's disease: a PMDAlliance survey.

Neuropsychiatr Dis Treat 2019 5;15:2205-2212. Epub 2019 Aug 5.

Department of Neurology, USF Health Parkinson's Disease and Movement Disorders Center, Parkinson Foundation Center of Excellence, Tampa, FL, USA.

Purpose: Parkinson's disease (PD) is associated with non-motor symptoms (NMS) that can cause progressive disability and impact quality of life of people with PD (PwP) and increase burden on care partners. This survey was designed to evaluate the prevalence, impact, and educational preferences regarding NMS on PwP and their care partners.

Patients And Methods: A 17-question survey was sent to the total membership of PMDAlliance, a nonprofit organization reaching 3,685 households of PwP. Care partners and other interested individuals could also respond. The survey was conducted using Survey Monkey, an online survey platform, and included distinct questions for respondents with and without NMS.

Results: A total of 700 individuals responded to the survey. Of the respondents, 378 (54%) were care partners and 287 (41%) were PwP. About 90% of the respondents reported having experience with NMS in PwP, including sleep problems (84%), cognitive symptoms (76%), anxiety (65%), depression (56%), hallucinations (40%), and delusions (23%). NMS in PwP were reported by more care partners (97%) than PwP (80%). NMS had at least some impact on quality of life for 84% of the respondents; 48% indicated that NMS represented a greater challenge than motor symptoms. Care partners were more likely than PwP to report that NMS were more challenging than motor symptoms (58% vs 32%). Respondents with and without NMS indicated a desire for NMS education.

Conclusion: This survey underscores the significant impact of NMS on the quality of life of PwP and highlights the need for improved recognition and education about its effects.
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http://dx.doi.org/10.2147/NDT.S213917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689087PMC
August 2019

Patient and physician perceptions of disease management in Parkinson's disease: results from a US-based multicenter survey.

Neuropsychiatr Dis Treat 2019 30;15:1487-1495. Epub 2019 May 30.

UCB Pharma, Smyrna, GA, USA.

Clinical care for patients with Parkinson's disease (PD) is complex, and disconnect may exist between patient and physician perceptions of treatment, disease awareness, and impact on quality of life (QoL). Relatively few studies have analyzed patient and physician perspectives of disease management concurrently, and even fewer have compared responses between corresponding patients and their physicians. This study aimed to characterize these aspects and identify opportunities to improve alignment. This cross-sectional study used an online survey and chart review. Participating physicians completed a profiling survey, followed by patient record forms (PRFs) for their next five patients with PD. Patients completed paper questionnaires. PRFs were matched with patient questionnaires, and patient and physician responses compared. Of 107 participating physicians, 70 completed 350 PRFs. Patients completed 71 questionnaires; 66 were matched to PRFs. From a physician perspective, there was alignment between the motor symptoms that were most bothersome for patients and those that were most discussed (physicians felt tremor was most bothersome for most patients [71%]; 77% of physicians included tremor among top three most discussed), but disconnect between the most bothersome and most discussed nonmotor symptoms (physicians felt fatigue was most bothersome for most patients [35%]; cognitive impairment was the most discussed nonmotor symptom, with 52% of physicians including it in top three most discussed). Patients and physicians reported moderate satisfaction with current PD medication. Patients considered form of delivery more important than did physicians. Physicians showed a strong level of awareness of PD's impact on patient QoL, although validated QoL instruments were not widely used. Physicians were more confident than patients about patients' awareness of support resources for patients with PD. Nonmotor symptoms, form of medication delivery, and awareness of support services are areas where PD physician and patient alignment could be increased to improve outcomes.
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http://dx.doi.org/10.2147/NDT.S196930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551617PMC
May 2019

Changing the treatment paradigm for Parkinson's disease psychosis with pimavanserin.

Expert Rev Clin Pharmacol 2019 Jul 13;12(7):681-691. Epub 2019 Jun 13.

e Parkinson's Disease and Movement Disorders Center of Boca Raton , Boca Raton , FL , USA.

: Parkinson's disease psychosis (PDP) may affect up to 60% of patients with Parkinson's disease over the course of their disease, and is associated with poor prognosis, including increased risks of mortality and nursing home placement. PDP treatments have been limited to off-label use of atypical antipsychotics, most of which pose risks of worsened motor symptoms and other potential adverse events (AEs) due to their dopamine receptor blockade and additional off-target receptor affinities. Pimavanserin is a highly selective 5-HT inverse agonist and poses no known risks for worsening of parkinsonism or other off-target receptor AEs. Pimavanserin is the first and only medication approved for PDP treatment. : This review covers estimated prevalence, clinical characteristics, diagnostic criteria, and risk factors for PDP; the hypothetical progression of PDP; management of PDP including use of antipsychotics; pharmacology and clinical trial data on pimavanserin; and expert opinion on PDP treatment. The NLM/PubMed database was searched for papers using the search terms of "PDP" AND "treatment" AND "pimavanserin" for the last 10 years. : The recent insights into PDP pathophysiology and approval of the only medication specifically to treat PDP are key advances that should improve the recognition, diagnosis, and management of PDP.
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http://dx.doi.org/10.1080/17512433.2019.1623669DOI Listing
July 2019

Neurological commentary addressing the article titled "Guidance for switching from off-label antipsychotics to pimavanserin for Parkinson's disease psychosis: an expert consensus".

Authors:
Neal Hermanowicz

CNS Spectr 2018 12;23(6):352-354

Department of Neurology,University of California-Irvine,Irvine,California,USA.

Parkinson's disease psychosis (PDP) occurs commonly and can comprise the most troubling symptoms among the many that occur with this illness. Prior treatment options for PDP have been limited and unsatisfactory due to uneven efficacy data, burdensome monitoring, and lack of a specific FDA indication coupled with warnings of increased mortality. Pimavanserin, approved for the treatment of PDP by the FDA in 2016, overcomes some of these obstacles, with data proven efficacy and without the frequent monitoring required for clozapine. This presents an opportunity to transition patients with PDP to pimavanserin from older therapies. Black and colleagues provide their thoughtful recommendations on how to achieve this transition to pimavanserin while maintaining symptom control and minimizing disruptions that might occur with a medication change.
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http://dx.doi.org/10.1017/S1092852918001165DOI Listing
December 2018

Delusional misidentification in Parkinson's disease: report of two cases and a review.

Authors:
Neal Hermanowicz

Postgrad Med 2018 Mar 13;130(2):280-283. Epub 2017 Dec 13.

a Irvine - Neurology , University of California , Irvine , CA , USA.

Syndromes of delusional misidentification consist of disordered familiarity and have been reported in diverse diagnoses, including Parkinson's disease. Although the most common delusional misidentification is Capgras syndrome, in which the sufferer believes a familiar person has been replaced by an identical imposter, other forms have been also described. The pathogenesis of delusions of misidentification appears to require dysfunction of or connection to a left cerebral cortical area involved in recognition of familiarity, and also right frontal cortex serving belief evaluation. Two cases of Parkinson's disease with an unusual delusional misidentification, intermetamorphosis, are presented, along with their improvement with pimavanserin, a novel atypical antipsychotic medication.
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http://dx.doi.org/10.1080/00325481.2018.1411161DOI Listing
March 2018

The Emerging Role of Pimavanserin in the Management of Parkinson's Disease Psychosis.

J Manag Care Spec Pharm 2017 Jun;23(6-b Suppl):S2-S8

11 Magellan Rx Management, Newport, Rhode Island.

A panel of experts drawn from neurology, psychiatry, geropsychiatry, geriatrics, and pharmacy representatives of 3 health plans convened in New York City on July 30, 2016, with the objective of sharing opinions, ideas, and information regarding the optimal management of Parkinson's disease psychosis (PDP). Three key points emerged from the discussion: (1) Because of the nature of Parkinson's disease and PDP, finding appropriate treatment can prove challenging; (2) emerging therapies may present an opportunity for effective disease management; and (3) moving forward, provider and patient education regarding PDP and available treatment options is essential for well-managed symptoms and better quality of life. The panel reviewed current practices and formulated recommendations on moving forward in the treatment of PDP.

Disclosures: This project and manuscript was funded by ACADIA Pharmaceuticals and developed by Magellan Rx Management. Lopes and Farnum are employees of Magellan Rx Management. Kremens has received consulting/speaker fees from Teva Pharmaceuticals, UCB, Sunovion, Impax, Lundbeck, ACADIA, USWorldMeds, Merz, Acorda, Kyowa, Neurocrine, and GE Healthcare. Pagan reports consulting/speaker fees from Teva Nanoscience, AbbVie, Impax, ACADIA, Medtronic, USWorldMeds, Merz, and Cynapsus and research and educational grants from USWorldMeds, Teva, and Medtronic. Patel has received consultant/speaker fees from ACADIA, Allergen, and Avanir. Alva reports research support from Accera, Allergan, Axovant, Eisai, Neurotrope, Genentech, Intra Cellular, Janssen, Lundbeck, Neurim, Novartis, Otsuka, Roche, Suven, and Trans Tech and consultant/speaker fees from ACADIA, Alkermes, Allergan, Avanir, Janssen, Lundbeck, Merck, Nestle, Otsuka, Sunovion, Takeda, and Vanda. The other authors report no potential conflicts of interest, financial or otherwise.
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http://dx.doi.org/10.18553/jmcp.2017.23.6-b.s2DOI Listing
June 2017

A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease.

Neurology 2017 Jan 2;88(2):152-159. Epub 2016 Dec 2.

From Cooper University Healthcare at Rowan University (A.M.), Camden, NJ; University of Rochester (M.M., K.K., E.A.d.B., K.B., P.C.); Weill Cornell Medical Center (F.B.); Columbia Presbyterian Medical Center (K.M.), New York, NY; Johns Hopkins Medical Center (C.R.), Baltimore, MD; Georgetown University (I.S.), Washington, DC; NINDS (P.G.), Bethesda, MD; Hereditary Neurological Disease Center (W.M.M.), Wichita, KS; The Centre for Movement Disorders (M.G.), Toronto, Canada; Indiana University School of Medicine (J.W.), Indianapolis; Colorado Neurological Institute (R.K.), Englewood; University of Tennessee Health Science Center (M.S.L.), Memphis; London Health Sciences Centre (M.J.), Canada; Massachusetts General Hospital (H.D.R.), Boston; Struthers Parkinson's Center (M.N.), Minneapolis, MN; University of Kansas Medical Center (R.M.D.), Kansas City; Rush University Medical Center (K.M.S.), Chicago, IL; University of Texas Southwestern Medical Center (P.O.), Dallas; University of Michigan (K.C.), Ann Arbor; Wake Forest University (F.W.), Winston-Salem, NC; University of Alberta (W.M.), Edmonton, Canada; University of California Davis (V.L.W.), Sacramento; Westmead Hospital (E. McCusker), Westmead, Australia; Baylor College of Medicine (J.J.), Houston, TX; University of Miami Miller School of Medicine (C.S.), FL; University of South Florida (J.S.-R.), Tampa; Duke University (B.S.), Durham, NC; University of Calgary (O.S.), Canada; Emory University School of Medicine (S.A.F.), Atlanta, GA; Albany Medical College (D.S.H., Eric Molho), NY; University of Cincinnati (F.R.), OH; Mayo Clinic Arizona (J.N.C.), Scottsdale; Butler Hospital (J.H.F.), Providence, RI; Washington University (J.S.P.), St. Louis, MO; Feinstein Institute for Medical Research (A.F.), Manhasset, NY; Georgetown University (K.A.), Washington, DC; University of Florida (R.R., N.R.M.), Gainesville; Johns Hopkins University (R.L.M.), Baltimore, MD; University of Nevada School of Medicine (E.S.F.), Reno; University of British Columbia (L.A.R.), Vancouver, Canada; University of Pittsburgh (V.S.), PA; Ohio State University (S.K.), Columbus; The Cooper University Health System (A.C.), Camden, NJ; Idaho Elks Rehabilitation Hospital (L.S.), Boise, ID; University of Iowa (E.E.), Iowa City; North York General Hospital 1 (S.E.), Toronto, Canada; St. Luke's Hospital (N.D.), Allentown, PA; North York General Hospital 2 (W.L.A.F.), University of Toronto, Canada; Washington Regional Medical Center (A.D.), Fayetteville, AR; Beth-Israel Deaconess Medical Center (S.F.), Boston, MA; NJ Neuroscience Institute (P.H.), Edison; University of California Irvine (N.H.); The University of Alabama at Birmingham (L.S.D.); and Massachusetts General Hospital (M.C.), Harvard Medical School, Boston.

Objective: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD.

Methods: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach.

Results: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study.

Conclusions: These data do not justify use of CoQ as a treatment to slow functional decline in HD.

Clinicaltrialsgov Identifier: NCT00608881.

Classification Of Evidence: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD.
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http://dx.doi.org/10.1212/WNL.0000000000003478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5224719PMC
January 2017

Clinical utility of DaTscan™ imaging in the evaluation of patients with parkinsonism: a US perspective.

Expert Rev Neurother 2017 03 23;17(3):219-225. Epub 2016 Nov 23.

g Institute for Neurodegenerative Disorders , New Haven , CT , USA.

Introduction: Single photon emission computed tomography (SPECT) with Ioflupane I123 injection (DaTscan™) was approved by the Food and Drug Administration in 2011 for striatal dopamine transporter visualization to assist in the evaluation of adult patients with suspected parkinsonian syndromes. While brain SPECT imaging using DaTscan is a covered service under Medicare policy, there is a lack of consensus on its role in routine clinical practice in the US. Areas covered: To address this issue, an expert group of US-based movement disorders neurologists convened to discuss the clinical utility of DaTscan in movement disorders practices within the US. The group identified and discussed routine clinical scenarios where imaging with DaTscan can provide useful information that may impact management and/or clarify clinical diagnoses. This paper summarizes a consensus reached by the expert group at this meeting. Expert commentary: The major utility of DaTscan imaging is the assistance it provides in distinguishing between nigrostriatal dopaminergic degeneration and non-nigrostriatal degeneration in patients displaying equivocal signs and symptoms of parkinsonism.
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http://dx.doi.org/10.1080/14737175.2017.1256205DOI Listing
March 2017

The Effect of Gabapentin Enacarbil on Pain Associated with Moderate-to-Severe Primary Restless Legs Syndrome in Adults: Pooled Analyses from Three Randomized Controlled Trials.

CNS Drugs 2016 05;30(5):443-54

XenoPort, Inc., Medical Affairs, Santa Clara, CA, USA.

Background: Adults with moderate-to-severe primary restless legs syndrome (RLS) often experience painful dysesthesias, which may lead to impaired quality of life.

Objectives: The aim of this study was to assess the effects of gabapentin enacarbil (GEn) on pain associated with moderate-to-severe primary RLS in adults.

Methods: Data were pooled from three double-blind, randomized, placebo-controlled, 12-week trials (NCT00298623, NCT00365352, NCT01332305) for adults receiving GEn or placebo once daily. Change in average daily RLS pain score and a combined International Restless Legs Scale (IRLS)-pain response were examined.

Results: The modified intention-to-treat population included 671 adults (placebo, n = 244; GEn 600 mg, n = 161; GEn 1200 mg, n = 266). Both GEn doses significantly improved average daily RLS pain score at week 12 (p < 0.001 for GEn 600 mg vs. placebo and GEn 1200 mg vs. placebo). The combined IRLS-pain response subanalysis included 366 patients with a baseline IRLS total score ≥15 and pain score ≥4 (placebo, n = 133; GEn 600 mg, n = 86; GEn 1200 mg, n = 147). Most patients were both IRLS and pain responders (placebo, 40 %; GEn 600 mg, 70 %; GEn 1200 mg, 67 %). Spearman rank correlations between IRLS total and pain score (change from baseline to week 12) were moderate or strong. The most frequent treatment-emergent adverse events were somnolence (placebo, 5 %; GEn 600 mg, 20 %; GEn 1200 mg, 23 %) and dizziness (placebo, 4 %; GEn 600 mg, 13 %; GEn 1200 mg, 22 %).

Conclusions: This post hoc pooled analysis suggests that GEn (600 and 1200 mg) once daily significantly improved pain associated with moderate-to-severe primary RLS in adults; however, the analysis was not powered to detect statistical differences between the two GEn doses. Numerically, more GEn-treated patients had a combined IRLS-pain response than placebo-treated patients.
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http://dx.doi.org/10.1007/s40263-016-0333-8DOI Listing
May 2016

The safety, tolerability and efficacy of pimavanserin tartrate in the treatment of psychosis in Parkinson's disease.

Expert Rev Neurother 2016 06;16(6):625-33

b Department of Neurology , School of Health Sciences, University of California , Irvine , CA , USA.

Parkinson's disease psychosis (PDP) is a common and often very disturbing component of Parkinson's disease (PD). PDP consists of hallucinations that are mainly visual and delusions that are often of a paranoid nature. These symptoms can be the most troubling and disruptive of all the manifestations of Parkinson's disease. Current treatment methods include the reduction of anti-Parkinson's medications, a strategy that may worsen the motor problems the medications are prescribed to alleviate, and the introduction of selected antipsychotic medications that carry with them the potential for troubling side effects and serious consequences. Pimavanserin has been developed and studied in clinical trials to specifically address Parkinson's disease psychosis and has been submitted to the U.S. Food and Drug Administration for its approval for this purpose. If this is granted, we believe the evidence of Pimavanserin efficacy, safety and tolerability will position this medication as the first choice for treatment of Parkinson's disease psychosis.
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http://dx.doi.org/10.1586/14737175.2016.1158102DOI Listing
June 2016

Effect of prior exposure to dopamine agonists on treatment with gabapentin enacarbil in adults with moderate-to-severe primary restless legs syndrome: pooled analyses from 3 randomized trials.

J Clin Mov Disord 2015 30;2. Epub 2015 Mar 30.

XenoPort, Inc., 3410 Central Expressway, Santa Clara, CA 95051 USA.

Background: Dopamine agonists (DAs) are a first-line therapy for moderate-to-severe restless legs syndrome (RLS), but these treatments may lead to complications, such as augmentation and impulse control disorders, requiring switching to another therapeutic class. Here we assess efficacy and tolerability of gabapentin enacarbil (GEn) in adults with moderate-to-severe primary RLS, with or without prior DA exposure.

Methods: Data from 3 trials were pooled. Patients were identified as DA-naive or DA-exposed, based on prior treatment with ropinirole, pramipexole, rotigotine, or pergolide mesylate, and the dopamine precursor levodopa. Details on prior treatment duration and dose were unavailable. Patients with a history of augmentation were excluded. Within DA-naive/DA-exposed patients we investigated the co-primary end points from the pivotal trials: mean change from baseline to week 12 in International RLS (IRLS) Rating Scale total score and proportion of responders ("much"/"very much" improved) on the investigator-rated Clinical Global Impression-Improvement (CGI-I) scale. Safety was also assessed.

Results: 671 patients were randomized (DA-naive: placebo, n = 194; GEn 600 mg, n = 131; GEn 1200 mg, n = 214; DA-exposed: placebo, n = 50; GEn 600 mg, n = 30; GEn 1200 mg, n = 52). Across treatment arms, no significant differences between DA-naive and DA-exposed subgroups in IRLS Rating Scale total score change from baseline at any visit were seen, except week 1 in the placebo group (-6.1 DA-naive vs -3.4 DA-exposed, P = .020). No significant differences in the odds of CGI-I response at week 12 between DA-naive vs DA-exposed patients in any treatment group were seen; however, with placebo there was a nonsignificant trend toward fewer responders among DA-exposed (34.0%) vs DA-naive (44.3%) patients. Both GEn doses significantly improved the IRLS Rating Scale total score change from baseline and CGI-I response vs placebo, regardless of prior DA exposure. The most common treatment-emergent adverse events were dizziness and somnolence.

Conclusions: Prior DA exposure had no significant effect on efficacy or tolerability of GEn (600 or 1200 mg) in this pooled analysis of adults with moderate-to-severe primary RLS. These data support the use of GEn in DA-exposed and DA-naive patients.

Trial Registration: ClinicalTrials.gov NCT00298623, NCT00365352, and NCT01332305.
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http://dx.doi.org/10.1186/s40734-015-0018-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711039PMC
January 2016

Frameless Stereotactic Robot-Assisted Subthalamic Nucleus Deep Brain Stimulation: Case Report.

World Neurosurg 2017 Jan 14;97:762.e11-762.e14. Epub 2015 Nov 14.

Department of Neurological Surgery, University of California, Irvine, Orange, California, USA. Electronic address:

Background: Electrode implantation for deep brain stimulation (DBS) can be performed in numerous ways, but the current "gold standard" is the use of frame-based systems for accuracy. Robotic stereotactic procedures, however, have gained increased interest because of their ease of use and reliability, but there could be concern about their safety in the United States as the result of recent lawsuits (e.g., the da Vinci Surgical System). We report the first DBS implantation performed using a robot (ROSA robotic device) approved by Food and Drug Administration for use in North America.

Case Description: A 56-year-old, right-handed woman with a 12-year history of Parkinson disease is described. She was offered bilateral subthalamic nucleus DBS placement to address motor fluctuations and dyskinesias. DBS electrode implantation was implemented successfully with ROSA robotic stereotactic assistance. Using preoperative magnetic resonance imaging scan acquisitions, we targeted the patient's subthalamic nucleus bilaterally. Bone fiducials were placed and intraoperative computed tomography (CT) imaging was obtained. The magnetic resonance imaging and CT were fused, and the patient was registered to the ROSA software. Trajectories were obtained and a microdrive device was fixed to the robotic arm to advance the electrode to the correct location. Electrodes were then placed bilaterally. Intraoperative CT showed good placement with no complications encountered.

Conclusions: The advantages of robotic assistance in stereotactic procedures are as follows: 1) improved accuracy, 2) "arc-less" approach, and 3) minor adjustments can be made in multiple planes to the entry point without adjustment of a frame. The case demonstrates robotic stereotactic assistance viability as an alternative to traditional frame-based or frameless systems in U.S. hospitals.
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http://dx.doi.org/10.1016/j.wneu.2015.11.009DOI Listing
January 2017

Parkinson's disease psychosis: symptoms, management, and economic burden.

Am J Manag Care 2015 Aug;21(10 Suppl):s199-206

Parkinson’s disease psychosis (PDP) is a costly,debilitating condition that generally develops several years after diagnosis of Parkinson’s disease (PD).PD is the second-most common neurodegenerative disease, and it imposes a significant burden on the healthcare system. Non-motor symptoms commonly manifest in PD, contributing to the severity of a patient’s disability. The neuropsychiatric symptoms that are common in PD can be a significant source of distress to patients and caregivers. Recent studies have shown that more than 50% of patients with PD will develop psychosis at some time over the course of the disease. The responsibility for caring for a person with PDP frequently falls on family members. Caregiver distress is frequently predicted when patients with PD have symptoms of psychosis.Hallucinations and delusions are independent predictors of nursing home placement for patients with PDP. The authors sought to examine total healthcare expenditures among patients with PDP compared with patients with PD without psychosis.All costs were higher for patients with PDP than for those with PD without psychosis and all-Medicare cohorts, with the highest cost differentials found in long-term care costs ($31,178 for PDP vs $14,461 forPD without psychosis), skilled nursing facility costs($6601 for PDP vs $2067 for PD without psychosis),and inpatient costs ($10,125 for PDP vs $6024 for PD without psychosis). Patients with PDP spent an average of 179 days in long-term care, compared with 83 days for patients with PD without psychosis. As expected, long-term care utilization and expenditures were significantly higher for patients with PDP than for patients with PD without psychosis. Reducing long-term care utilization by patients with PDP may significantly lower the overall economic burden associated with PDP.
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August 2015

Colorectal surgery in Parkinson's disease--outcomes and predictors of mortality.

Int J Colorectal Dis 2015 Aug 4;30(8):1051-8. Epub 2015 Jun 4.

Department of Surgery, Irvine School of Medicine, University of California, Irvine, Orange, CA, USA.

Purpose: Although diseases of the lower gastrointestinal tract are common in patients with Parkinson's disease, there is a paucity of data regarding postoperative outcomes after colorectal surgery.

Methods: The Nationwide Inpatient Sample database (2007-2011) was utilized to analyze outcomes in patients with Parkinson's disease (PD) undergoing colorectal surgery. Main outcomes were risk-adjusted inpatient morbidity, mortality, hospital charge, and length of hospital stay.

Results: A total of 6490 patients were identified. Utilization of laparoscopic surgery in Parkinson's patients has progressively increased in frequency over the latest 5 years analyzed. The most common diagnoses were colorectal malignancy (39 %) and intestinal obstruction (20 %). Right hemicolectomy (37 %) and sigmoidectomy (30 %) were the most common operations. Laparoscopy was used in 18 % of Parkinson's patients and most commonly in the elective setting. 54.3 % of Parkinson's patients had emergency surgery compared to 38.6 % in non-Parkinson's. Overall morbidity and mortality were significantly lower after laparoscopic surgery compared to open (20 vs. 25 % and 2.1 vs. 6.6 %, respectively). Length of stay was significantly shorter (OR -1.86; p < 0.01) for laparoscopic operations, but there were no significant differences in risk-adjusted outcomes between laparoscopic and open groups.

Conclusion: PD patients have high rates of morbidity and mortality after colorectal surgery; this may be because more than half of all patients in this population undergo emergent surgery. The laparoscopic approach appears to have short-term benefits in this patient population.
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http://dx.doi.org/10.1007/s00384-015-2256-0DOI Listing
August 2015

A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit.

JAMA Neurol 2014 May;71(5):543-52

Columbia University Medical Center, Neurological Institute, New York, New York.

Importance: Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit.

Objective: To examine whether CoQ10 could slow disease progression in early PD.

Design, Setting, And Participants: A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation.

Interventions: The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E.

Main Outcomes And Measures: Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo.

Results: The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo).

Conclusions And Relevance: Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit.

Trial Registration: clinicaltrials.gov Identifier: NCT00740714.
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http://dx.doi.org/10.1001/jamaneurol.2014.131DOI Listing
May 2014

A synthetic cannabinoid agonist promotes oligodendrogliogenesis during viral encephalitis in rats.

Exp Neurol 2010 Nov 9;226(1):231-41. Epub 2010 Sep 9.

Department of Medicine (Neurology), University of Manitoba, Winnipeg, Manitoba, Canada.

Chronic CNS infection by several families of viruses can produce deficits in prefrontal cortex (PFC) and striatal function. Cannabinoid drugs have been long known for their anti-inflammatory properties and their ability to modulate adult neuro and gliogenesis. Therefore, we explored the effects of systemic administration of the cannabinoid agonist WIN55,212-2(WIN) on prefrontal cortex (PFC) and striatal cytogenesis in a viral model of CNS injury and inflammation based on Borna Disease (BD) virus encephalitis. Active BrdU(+) progenitor populations were significantly decreased 1 week after BrdU labeling in BD rats [p<0.001 compared to uninfected (NL) controls] while less than 5% of BrdU(+) cells colabeled for BDV protein. Systemic WIN (1mg/kg i.p. twice daily×7 days) increased the survival of BrdU(+) cells in striatum (p<0.001) and PFC of BD rats, with differential regulation of labeled oligodendroglia precursors vs microglia/macrophages. WIN increased the percentage of BrdU(+) oligodendrocyte precursor cells and decreased BrdU(+) ED-1-labeled phagocytic cells, without producing pro- or antiviral effects. BDV infection decreased the levels of the endocannabinoid anandamide (AEA) in striatum (p<0.05 compared to NL rats), whereas 2-AG levels were unchanged. Our findings indicate that: 1) viral infection is accompanied by alterations of AEA transmission in the striatum, but new cell protection by WIN appears independent of its effect on endocannabinoid levels; and 2) chronic WIN treatment alters the gliogenic cascades associated with CNS injury, promoting oligodendrocyte survival. Limiting reactive gliogenesis and macrophage activity in favor of oliogodendroglia development has significance for demyelinating diseases. Moreover, the ability of cannabinoids to promote the development of biologically supportive or symbiotic oligodendroglia may generalize to other microglia-driven neurodegenerative syndromes including NeuroAIDS and diseases of aging.
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http://dx.doi.org/10.1016/j.expneurol.2010.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981070PMC
November 2010

Inhibition of glyceraldehyde-3-phosphate dehydrogenase activity by antibodies present in the cerebrospinal fluid of patients with multiple sclerosis.

J Immunol 2010 Aug 7;185(3):1968-75. Epub 2010 Jul 7.

Department of Neurology, University of California at Irvine, Irvine, CA 92697, USA.

We have previously shown that B cells and Abs reactive with GAPDH and antitriosephosphate isomerase (TPI) are present in lesions and cerebrospinal fluid (CSF) in multiple sclerosis (MS). In the current study, we studied the effect of anti-GAPDH and anti-TPI CSF IgG on the glycolytic enzyme activity of GAPDH and TPI after exposure to intrathecal IgG from 10 patients with MS and 34 patients with other neurologic diseases. The degree of inhibition of GAPDH activity by CSF anti-GAPDH IgG in the seven MS samples tested varied from 13 to 98%, which seemed to correlate with the percentage of anti-GAPDH IgG in the CSF IgG (1-45%). Inhibition of GAPDH activity (18 and 23%) by CSF IgG was seen in two of the 34 patients with other neurologic diseases, corresponding to the low percentage of CSF anti-GAPDH IgG (1 and 8%). In addition, depletion of anti-GAPDH IgG from CSF IgG, using immobilized GAPDH, removed the inhibitory effect of the IgG on GAPDH. No inhibition of GAPDH activity was seen with CSF samples not containing anti-GAPDH IgG. No inhibition of TPI activity was seen with any purified CSF IgG sample. These findings demonstrate an increased percentage of anti-GAPDH Abs in the CSF of patients with MS that can inhibit GAPDH glycolytic enzyme activity and may contribute to neuroaxonal degeneration.
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http://dx.doi.org/10.4049/jimmunol.0904083DOI Listing
August 2010

Increased prevalence of val(66)met BDNF genotype among subjects with cervical dystonia.

Neurosci Lett 2010 Jan 24;468(1):42-5. Epub 2009 Oct 24.

Department of Neurology, University of California, Irvine, CA, USA.

Abnormalities of cortical representational maps and their plasticity have been described in dystonia. A common polymorphism for BDNF has been associated with abnormal cortical plasticity, and thus might contribute to pathogenesis of dystonia in some subjects. As a first step towards this suggestion, the current study examined the prevalence of this polymorphism. BDNF genotype was examined in 34 subjects with cervical dystonia, 54 age-matched healthy controls, and 53 subjects with a different movement disorder, Parkinson's disease. ApoE genotype, known to influence neurological outcome in some conditions, was also examined as a control. In subjects with cervical dystonia, the val(66)met polymorphism was approximately twice as prevalent when compared to either control group. This was not true of ApoE genotype, which was similarly distributed across subject groups. The current findings suggest that the BDNF val(66)met polymorphism might play a role in the pathogenesis of cervical dystonia in some subjects.
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http://dx.doi.org/10.1016/j.neulet.2009.10.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270368PMC
January 2010

Orally disintegrating selegiline in Parkinson patients with dopamine agonist-related adverse effects.

Clin Neuropharmacol 2010 Jan-Feb;33(1):5-10

University of Kansas Medical Center, Kansas City, KS 66160, USA.

Objective: To determine whether adding orally disintegrating selegiline (ODS) while decreasing dopamine agonist (DA) dosages would reduce DA-related adverse effects (AEs) of excessive daytime sleepiness (EDS), pedal edema, hallucinations, and impulse control disorders (ICDs) without compromising efficacy in Parkinson disease (PD) patients.

Methods: This was a 12-week open-label study of 60 PD patients with motor fluctuations and DA-related AEs of EDS, pedal edema, hallucinations, and ICDs. Orally disintegrating selegiline was initiated at 1.25 mg once daily, and down titration of the DA was started with a goal of a 50% reduction by 1 week. At week 6, ODS was increased to 2.5 mg, and further reductions of the DA were allowed if the AEs were not resolved.

Results: The addition of ODS allowed a reduction in the mean daily dose of pramipexole from 2.3 to 0.5 mg and immediate-release ropinirole from 11.2 to 2.9 mg. Most subjects reported a reduction or resolution of DA-related AEs; 94% with EDS (n = 50), 73% with pedal edema (n = 26), 86% with hallucinations (n = 15), and 84% with ICDs (n = 25). Mean activities of daily living and motor scores from the Unified Parkinson's Disease Rating Scale as well as quality-of-life scores were significantly improved without an increase in daily "off" time. The most common AEs, most of which resolved after titration, were worsening of PD, nausea/vomiting, dyskinesia, increased off time, body aches, insomnia, orthostatic hypotension, and increased anxiety and depression.

Conclusions: In most subjects, the addition of ODS with decreasing dosages of DAs substantially reduced EDS, pedal edema, hallucinations, and ICDs without compromising efficacy.
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http://dx.doi.org/10.1097/WNF.0b013e3181b7926fDOI Listing
April 2010

A forty-five year follow-up EEG study of Qigong practice.

Int J Neurosci 2009 ;119(4):538-52

Institue of Neurology, Huashan Hospital, Fudan University, Shanghai, China.

A follow-up EEG study was conducted on a subject with 50 years of experiences in Qigong. Resting EEG at present showed frontally dominant alpha-1 as compared to occipitally dominant alpha-2 described in 1962. During the Qigong practice alph-1 enhanced quickly and became far more prominent than 50 years ago. Compared with baseline, these activities remained to be higher at rest after the Qigong practice. These results suggest that extended practice in meditation may change the EEG pattern and its underlying neurophysiology. It remains to be explored as to what biological significance and clinical relevance do these physiological changes might mean.
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http://dx.doi.org/10.1080/00207450802325520DOI Listing
April 2009

Cannabinoid rescue of striatal progenitor cells in chronic Borna disease viral encephalitis in rats.

J Neurovirol 2008 May;14(3):252-60

Department of Neurology, University of California-Irivne, Irvine, California 92697-4292, USA.

A growing number of environmental and pharmacologic manipulations have been shown to influence adult neurogenesis. Borna disease virus (BDV) in rats causes cortical and subcortical infection with extrapyramidal motor symptoms, and hippocampal infection suppresses neurogenesis. Given the known effects of cannabinoids in promoting neural progenitor cell survival, the authors examined in vivo effects of chronic BDV infection in rats on BrdU-positive progenitor cells in striatum, together with neuroprotective actions of cannabinoids. Birth and survival of BrdU-positive progenitor cells in striatum of BDV-infected rats treated with a general cannabinoid agonist (WIN 55,212 1 mg/kg i.p. b.i.d. x 7 days) were examined, as well as anti-inflammatory, antiviral, and nutritional effects of cannabinoids. Cannabinoid treatment protected BrdU-positive progenitor cells in striatum that were susceptible to virus-induced injury (p < .01) through suppression of microglia activation (p < .001). As a consequence of their anti-inflammatory actions and support of neural progenitor cell survival, cannabinoids may be adjunctive treatment for encephalitides with microglial inflammation and neurodegeneration.
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http://dx.doi.org/10.1080/13550280802074521DOI Listing
May 2008

Fatal gastroparesis in a patient with Parkinson's disease.

Authors:
Neal Hermanowicz

Mov Disord 2008 Jan;23(1):152-3

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http://dx.doi.org/10.1002/mds.21767DOI Listing
January 2008

Rasagiline as a therapy for Parkinson's disease (PD).

Authors:
Neal Hermanowicz

Am J Geriatr Pharmacother 2007 Jun;5(2):174-5; author reply 175-6

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http://dx.doi.org/10.1016/j.amjopharm.2007.06.002DOI Listing
June 2007

Drug therapy for Parkinson's disease.

Authors:
Neal Hermanowicz

Semin Neurol 2007 Apr;27(2):97-105

Department of Neurology, Movement Disorders Program, University of California-Irvine 92697-4275, USA.

The fundamental concepts of the medical treatment of Parkinson's disease are simple, and remain based on the enhancement of dopaminergic transmission by means of levodopa and dopamine agonists. Recently published practice parameters from the American Academy of Neurology and an evidence-based review under the auspices of the Movement Disorder Society provide guidance on motor complications and also cognitive and psychiatric issues associated with Parkinson's disease. The choices of medications are increasing as are the routes of administration, with the arrival of injectable and transdermal dopamine agonists and a monoamine inhibitor absorbed via the buccal mucosa. Although simple conceptually, the actual care of patients with Parkinson's disease is often complex, requiring consideration of potential future complications and individualized medication regimens, and minimizing the adverse effects of medications that range from unpleasant to seriously disturbing.
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http://dx.doi.org/10.1055/s-2007-971177DOI Listing
April 2007

Reduction of EEG myogenic artifact with botulinum toxin during video-EEG monitoring.

Epilepsia 2007 Feb;48(2):324-9

Departments of Neurology, New York University, New York, New York 10016, USA.

Purpose: To determine whether EEG myogenic artifact during video-EEG monitoring (VEM) is reduced with targeted scalp botulinum toxin (BTX-A) injections.

Methods: Twelve consecutive patients scheduled for presurgical VEM were treated 2-3 weeks before admission with subcutaneous BTX-A injections at specific EEG electrode locations. On the basis of clinical data available before VEM, four subjects were treated unilaterally (group 1) and eight bilaterally (group 2). BTX-A efficacy was assessed quantitatively in group 1 subjects by comparing high-frequency (20-100 Hz) power at homologous "treated" and "untreated" electrodes during voluntary forceful jaw closure. The clinical impact of BTX-A treatment was assessed by determining whether > or =5 of the first 10 s of each ictal recording was obscured by muscle artifact, and whether residual myogenic artifact on BTX-A-"treated" electrodes rendered these ictal EEG segments impossible to interpret.

Results: BTX-A treatment reduced high-frequency power by a mean of 53% at electrodes T3/T4 and 52% at electrodes F7/F8. None of 49 ictal EEGs had > or =5 of the first 10 s obscured by myogenic artifact, and all of these ictal epochs were interpretable. Adverse events were limited to two subjects who complained of transient difficulty chewing tough foods.

Conclusions: Scalp-muscle BTX-A treatment before VEM significantly reduces myogenic artifact in subsequent EEG recordings, including ictal EEG. The clinical utility of this technique for improved or more-rapid seizure localization will be determined only by large, blinded, prospective trials.
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http://dx.doi.org/10.1111/j.1528-1167.2006.00930.xDOI Listing
February 2007

Triosephosphate isomerase- and glyceraldehyde-3-phosphate dehydrogenase-reactive autoantibodies in the cerebrospinal fluid of patients with multiple sclerosis.

J Immunol 2006 Oct;177(8):5652-8

Department of Neurology, University of California, Irvine, CA 92697, USA.

Our previous results revealed that Igs in lesions and single chain variable fragment Abs (scFv-Abs) generated from clonal B cells in the cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) bind to axons in MS brains. To study the axonal Ags involved in MS, we identified the glycolytic enzymes, triosephosphate isomerase (TPI) and GAPDH, using Igs from the CSF and scFv-Abs generated from clonal B cells in the CSF and in lesions from MS patients. Elevated levels of CSF-Abs to TPI were observed in patients with MS (46%), clinically isolated syndrome (CIS) suggestive of MS (40%), other inflammatory neurological diseases (OIND; 29%), and other noninflammatory neurological diseases (ONIND; 31%). Levels of GAPDH-reactive Abs were elevated in MS patients (60%), in patients with CIS (10%), OIND (14%), and ONIND (8%). The coexistence of both autoantibodies was detected in 10 MS patients (29%), and 1 CIS patient (3%), but not in patients with OIND/ONIND. Two scFv-Abs generated from the CSF and from lesions of a MS brain showed immunoreactivity to TPI and GAPDH, respectively. The findings suggest that TPI and GAPDH may be candidate Ags for an autoimmune response to neurons and axons in MS.
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http://dx.doi.org/10.4049/jimmunol.177.8.5652DOI Listing
October 2006
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