C. W. Olanow

International Multicenter Pilot Study of the First Comprehensive Self-Completed Nonmotor Symptoms Questionnaire for Parkinson's Disease: The NMSQuest Study

Nonmotor symptoms (NMS) of Parkinsons disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of NMS and initiate further investigation. In this article, we present the results from an international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest). Data from 123 PD patients and 96 controls were analyzed. NMS were highly significantly more prevalent in PD compared to controls (PD NMS, median = 9.0, mean = 9.5 vs. control NMS, median = 5.5, mean = 4.0; Mann–Whitney, Kruskal–Wallis, and t test, P < 0.0001), with PD patients reporting at least 10 different NMS on average per patient. In PD, NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease. Furthermore, frequently, problems such as diplopia, dribbling, apathy, blues, taste and smell problems were never previously disclosed to the health professionals.

Use of placebo surgery in controlled trials of a cellular-based therapy for Parkinson's disease.

Surgical procedures are frequently introduced into general practice on the basis of uncontrolled studies that are less rigorous than those required for the approval of medical interventions.1 The s...

Perampanel, an AMPA Antagonist, Found to Have No Benefit in Reducing ''Off'' Time in Parkinson's Disease

Perampanel is a selective, noncompetitive α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionic acid receptor antagonist. Two multicenter randomized, double‐blind, placebo‐controlled, parallel‐group phase III studies assessed the efficacy and safety of adjunctive perampanel in patients with Parkinsons disease and motor fluctuations.

Past, Present, and Future of Parkinson's Disease: A Special Essay on the 200th Anniversary of the Shaking Palsy

This article reviews and summarizes 200 years of Parkinsons disease. It comprises a relevant history of Dr. James Parkinsons himself and what he described accurately and what he missed from todays perspective. Parkinsons disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple‐author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state‐of‐the‐art account of what has been achieved, the current situation, and how to progress toward resolving Parkinsons disease.

Intranigral iron infusion in the rat. Acute elevations in nigral lipid peroxidation and striatal dopaminergic markers with ensuing nigral degeneration.

Iron is known to induce lipid perocidation and recent evidence indicates that both iron and lipid peroxidation are elevated in the substantia nigra in Parkinsons disease (PD). To test whether excess intranigral iron induces lipid peroxidation, we infused an iron citrate solution (0.63 nmol in 0.25 μL) into the rat substantia nigra and measured nigral thiobarbituric acid reactive products at 1-h, 1-d, 1-wk, and 1-mo postinfusion. In a separate group of iron-infused animals, histologic analysis within the substantia nigra through 1-mo postinfusion was accomplished by thionine- and iron-staining, with concurrent assessment of striatal neurochemical markers. Concentrations of nigral thiobarbituric acid reactive products were significantly elevated at 1 h and 1 d in iron-infused animals compared to vehicle-infused and unoperated animals, with a return to control values by 1 wk. Similarly, striatal dopamine turnover was acutely elevated, suggesting damage to dopaminergic neurons, which was confirmed histologically. Although iron-staining within the iron diffusionary area was increased through the postinfusion month, there was an apparent progression of the cellular character of staining from predominantly neuronal to reactive glial and finally to oligodendroglial by 1 mo postinfusion. this progression of cellular iron-staining may indicate a shifting of infused iron to a more bound unreactive form, thus explaining only an acute elevation in lipid peroxidation through 1 d following intranigral iron infusion. The data indicate that damage to nigral neurons induced by iron infusion is transciently associated with a marker of oxidative damage and supports the possibility that iron-induced oxidative stress contributes to the pathogenesis of PD.

Treatment with fetal allografts

To the Editor: We were astonished by the report by Folkerth and Durso’ documenting the presence of bone, mature hyaline cartilage, hair shafts, and squamous epithelium with keratinous debris after placement of fetal tissue into the ventricular system of a patient with Parkinson’s disease. From the authors, we have learned that this patient had a surgical procedure performed in the United States in which an Ommaya reservoir was placed in the lateral ventricle. Subsequently, the patient traveled to China, where an American neurosurgeon grafted tissue from fetuses into the right caudate nucleus and left putamen. Then, through the Ommaya reservoir, a suspension from a third embryo was injected into the ventricular system. Twenty-three months later, this patient died, apparently from ventricular obstruction secondary to growth of the suspension implant. The ventricular obstruction may have caused brainstem compression. Scientifically, there were serious flaws in the choice of transplant variables. The patient received implants from two embryos, aged 16 weeks postconception. It is well established that this age is inappropriate for transplantation, because human donor cells older than postconception week 9.5 do not survive grafting.2 As expected, all grafted cells within the caudate nucleus and putamen died. The rationale for placing a suspension of fetal tissue into the ventricular system is misguided. Cells from this embryo would be expected to flow through the ventricular system rather than be specifically directed to target sites within the striatum. Indeed, the autopsy report demonstrates the presence of embryonic tissue in the fourth cerebral ventricle, remote from the transplant site. This apparently was the cause of death, underscoring the point’ that intraventricular suspension grafts are potentially dangerous. It is particularly critical to address the cellular origin of the bone, cartilage, hair, and the squamous epithelium. The authors suggest that the donor tissue might have been contaminated with tissue of ectodermal and mesodermal origin. We could not agree more. The intent of the surgical team was to dissect regions of “diencephalic and mesodiecephalic” origin. These are the wrong locations, because fetal nigral neurons are located within the ventral mesencephalon. This is a case of extremely poor tissue dissection, and the implanted tissue most likely comprised or included non-CNS structures. Lastly, one wonders why this transplant was performed in China, outside of State and Federal Regulations, Institutional Review Board Oversight, and peer review scrutiny. This patient came under the care of Dr. Durso over a year following the surgical procedure, and neither author was in any way involved with the design or the performance of the operation. Yet a number of points of data presentation and interpretation need to be addressed. First, the authors’ suggestion that transplanted neurons are pluripotent and could have differentiated and reorganized into bone, cartilage, and hair is biological fantasy. Such a transformation has never been demonstrated to occur. The citation of the classic work by Rosenstein and Brightman: which describes the developmentally appropriate “regression” of neurites following intraventricular ganglia implants, fails in any way to support this hypothesis. Second, the authors’ concern in this case about a “feared neuroplastic response” is not applicable to transplants of fetal nigral neurons in which biotransformation and neoplasia have never been described. Finally, we caution readers on the clinical data as presented by the authors. Statements regarding the patient’s clinical status are made without baseline data, appear to be based solely on patient and family reports, and do not include objective parkinsonian rating scales. Further, clinical evaluations postoperatively were confounded by manipulations in antiparkinsonian medications. The PET imaging information is also uninterpretable due to the lack of preoperative imaging. We agree with the authors that neural transplantation is still experimental. For this reason, we strongly recommend that a t the present time, fetal nigral grafts be performed only by groups with laboratory transplant experience and expertise in tissue dissec-

International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: The NMSQuest study: Nonmotor Symptoms and PD

Nonmotor symptoms (NMS) of Parkinsons disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of NMS and initiate further investigation. In this article, we present the results from an international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest). Data from 123 PD patients and 96 controls were analyzed. NMS were highly significantly more prevalent in PD compared to controls (PD NMS, median = 9.0, mean = 9.5 vs. control NMS, median = 5.5, mean = 4.0; Mann–Whitney, Kruskal–Wallis, and t test, P < 0.0001), with PD patients reporting at least 10 different NMS on average per patient. In PD, NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease. Furthermore, frequently, problems such as diplopia, dribbling, apathy, blues, taste and smell problems were never previously disclosed to the health professionals.

International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease

Nonmotor symptoms (NMS) of Parkinsons disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of NMS and initiate further investigation. In this article, we present the results from an international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest). Data from 123 PD patients and 96 controls were analyzed. NMS were highly significantly more prevalent in PD compared to controls (PD NMS, median = 9.0, mean = 9.5 vs. control NMS, median = 5.5, mean = 4.0; Mann–Whitney, Kruskal–Wallis, and t test, P < 0.0001), with PD patients reporting at least 10 different NMS on average per patient. In PD, NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease. Furthermore, frequently, problems such as diplopia, dribbling, apathy, blues, taste and smell problems were never previously disclosed to the health professionals.