Wayne Martin

• MD
• Professor Emeritus at University of Alberta

Objective: To evaluate the relationship between Parkinson's disease (PD) with dementia and cortical proteinopathies in a large population of pathologically confirmed PD patients. Methods: We reviewed clinical data from all patients with autopsy data seen in the Movement Disorders Center at Washington University, St. Louis between 1996 and 2019....

Background Gait impairment is a debilitating and progressive feature of Parkinson’s disease (PD). Increasing evidence suggests that gait control is partly mediated by cholinergic signaling from the pedunculopontine nucleus (PPN). Objective We investigated whether PPN structural connectivity correlated with quantitative gait measures in PD. Method...

BACKGROUND Gait impairments are common in Parkinson’s Disease (PD) and are likely caused by degeneration in multiple brain circuits, including the basal ganglia, thalamus and mesencephalic locomotion centers (MLC). Diffusion tensor imaging (DTI) assesses fractional anisotropy (FA) and mean diffusivity (MD) that reflect the integrity of neuronal mic...

Background The clinical diagnosis of Parkinson's disease (PD) requires the presence of parkinsonism and supportive criteria that include a clear and dramatic beneficial response to dopaminergic therapy. Our aim was to test the diagnostic criterion of dopaminergic response by evaluating its association with pathologically confirmed diagnoses in a la...

This study assessed how BDNF (brain-derived neurotrophic factor) and other genes involved in its signaling influence brain structure and clinical functioning in pre-diagnosis Huntington’s disease (HD). Parallel independent component analysis (pICA), a multivariate method for identifying correlated patterns in multimodal datasets, was applied to gra...

Magnetic resonance imaging of subcortical gray matter structures, which mediate behavior, cognition and the pathophysiology of several diseases, is crucial for establishing typical maturation patterns across the human lifespan. This single site study examines T1-weighted MPRAGE images of 3 healthy cohorts: (i) a cross-sectional cohort of 406 subjec...

Introduction: Supranuclear gaze palsy (SGP) is a classic clinical feature of progressive supranuclear palsy (PSP) but is not specific for this diagnosis and has been reported to occur in several other neurodegenerative parkinsonian conditions. Our objective was to evaluate the association between SGP and autopsy-proven diagnoses in a large populat...

Background: Parkinson's disease (PD), characterized by motor dysfunction and cognitive decline, may demonstrate specific patterns of brain atrophy. Although cross-sectional magnetic resonance imaging (MRI) studies show correlation between regional brain volume loss and cognitive impairment, there is only scarce evidence from longitudinal studies v...

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 Unite...

Background: Parkinson disease (PD) presents with motor and non-motor symptoms (NMS). The NMS often precede the onset of motor symptoms, but may progress throughout the disease course. Tremor dominant, postural instability gait difficulty (PIGD), and indeterminate phenotypes can be distinguished using Unified PD Rating scales (UPDRS-III). We hypothe...

Purpose: Freezing of gait is a major source of disability associated with the progression of Parkinson's disease (PD). Our objective was to determine whether evolving changes in nigral iron content in association with declining motor function in early PD differentiates subjects who develop freezing from those who do not. Methods: A cohort of pre...

Importance Identifying measures that are associated with the cytosine-adenine-guanine (CAG) expansion in individuals before diagnosis of Huntington disease (HD) has implications for designing clinical trials.Objective To identify the earliest features associated with the motor diagnosis of HD in the Prospective Huntington at Risk Observational St...

To determine whether, in patients with early Parkinson's disease (PD), longitudinal changes in midbrain iron content are associated with declining motor function over a period of three years. Nineteen untreated subjects with early PD and 13 age- and sex-matched controls were followed clinically for 36 months. MRI with a 3 T magnet was performed at...

In this work, a class of non-negative matrix factorization (NMF) technique known as alternating non-negative least squares, combined with the projected gradient method, is used to analyze twenty-five [11C]-DTBZ dynamic PET/CT brain data. For each subject, a two-factor model is assumed and two factors representing the striatum (factor 1) and the non...

Resting-state fMRI (RS-fMRI) is a noninvasive imaging technique that identifies brain regions exhibiting correlated patterns of spontaneously occurring, slow changes in brain activity that are present at rest.¹ This resting brain activity is observed with MRI through changes in blood flow referred to as a blood oxygen level–dependent (BOLD) signal....

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 cou...

(11)C-Pittsburgh compound B (PiB) PET is a sensitive and increasingly popular imaging tool for assessing the deposition of fibrillar β-amyloid aggregates in the brains of living patients with Alzheimer disease (AD). Increased cortical PiB binding also occurs in dementia with Lewy bodies, but rarely in cognitively impaired individuals with Parkinson...

We report a retrospective case series of four patients with genetically confirmed Huntington's disease (HD) and sporadic amyotrophic lateral sclerosis (ALS), examining the brain and spinal cord in two cases. Neuropathological assessment included a polyglutamine recruitment method to detect sites of active polyglutamine aggregation, and biochemical...

To estimate the age-specific incidence of Parkinson's disease (PD) in elderly persons in the Canadian province of British Columbia (BC). All-cause and injury mortalities and relative risk of death for those persons with PD were also examined. A historical cohort study was conducted using 5 provincial administrative databases from 1991/92 to 2000/20...

Diffusion tensor imaging (DTI) has been used widely to show structural brain changes during both development and aging. Lifespan studies are valuable because they connect these two processes, yet few DTI studies have been conducted that include both children and elderly subjects. This study used DTI tractography to investigate 12 major white matter...

Advances in imaging have made it possible to detect functional and, increasingly, structural changes in Parkinson's disease. Although imaging is not yet routinely used for diagnosis, such an application is becoming increasingly feasible. Of potentially greater interest, however, is the use of imaging as a biomarker to detect premotor disease and di...

Purpose: To apply factor analysis technique to a sequence of 11C‐DTBZ dynamic PET images to healthy and diseased subjects in order to extract factor curves (or time activity curves) and associated factor images and develop a metric to detect extent of Parkinsonˈs disease. Methods: Philips Gemini (C) PET/CT scanner (with 4mm isotropic voxels) is use...

Age-related ventricular enlargement is accelerated in Alzheimer's disease, but its relationship to cognitive decline in Parkinson's disease is less clear, even though dementia is common in Parkinson's disease. Our goals were to determine if greater enlargement of the ventricles and gray or white matter atrophy occurred in Parkinson's disease patien...

IntroductionCardinal FeaturesDifferential DiagnosisNon-Dopaminergic Features of PDNatural HistoryConclusions References

Part of the successful Institute of Health Economics (IHE) book series, this handbook and ready reference adopts a unique approach in combining policy recommendations with specific treatment options for Parkinson patients. The first part of the book deals with the clinical medical, social and economical aspects of Parkinson Disease. These ten chapt...

Overview of Research PolicyClinical ResearchReferences

Coordinate Neurological Services – Establish Specialized Centers Within a New FrameworkEstablish a Committee to Review the Management of People with Neurological DiseasesReferences

IntroductionPharmacologic TreatmentNursingRehabilitationNutritionPsychosocial IssuesConclusions References

We examined the gold standard for Huntington disease (HD) functional assessment, the Unified Huntington's Disease Rating Scale (UHDRS), in a group of at-risk participants not yet diagnosed but who later phenoconverted to manifest HD. We also sought to determine which skill domains first weaken and the clinical correlates of declines. Using the UHDR...

Aims Parkinson's disease (PD) constitutes a significant risk for falls and subsequent hip fracture, yet the rate of hip fracture in this patient population has not been clearly delineated. We looked at the incidence rate of hip fracture in a provincial-based population 65 years or older who had PD. Methods To identify PD cases record linkage of inp...

Biochemical studies have reported increased iron content in the substantia nigra pars compacta (SNc) in Parkinson disease (PD), with changes most marked in severe disease, suggesting that measurement of regional iron content in the nigra may provide an indication of the pathologic severity of the disease. Although basal ganglia structures, includin...

The purpose of this study was to determine if focal cortical abnormalities may occur in early Parkinson's disease (PD). We studied 26 untreated patients with early PD and 14 healthy control subjects, with cognitive screening and magnetic resonance imaging (MRI). Voxel-based morphometry was used to assess for the presence of localized cortical grey...

Objective: To determine whether ethyl-eicosapentaenoic acid (ethyl-EPA), an omega-3 fatty acid, improves the motor features of Huntington disease. Design: Six-month multicenter, randomized, double-blind, placebo-controlled trial followed by a 6-month open-label phase without disclosing initial treatment assignments. Setting: Forty-one research...

This Practice Point commentary discusses a prospective study by Gaenslen et al. regarding the diagnostic value of transcranial ultrasound in patients with early features of parkinsonism. Reference diagnoses were obtained on the basis of repeated clinical examination over the course of 1 year and by the performance of functional imaging in uncertain...

Although motor symptoms of Parkinson's disease (PD) are initially responsive to dopamine replacement therapy, nonresponsive features develop over time, suggesting that impaired dopaminergic function alone may not be wholly responsible for all the motor features of the disease. Previous studies suggest impaired function in the presupplementary motor...

While Parkinson's disease (PD) is associated with motor slowing, less attention has been paid to variability in performance on motor and cognitive tasks. To examine reaction time latencies and intraindividual variability in untreated patients with PD compared to healthy controls. Twenty-nine (19 men/10 women) patients with untreated PD and 16 contr...

The hippocampus (HC) and amygdala (AG) decrease in volume with age and in Parkinson's disease (PD) with (PDD) and without dementia. We compared 44 PD to 44 age, sex and education-matched subjects without PD (non-PD) and 13 PDD subjects. T1-weighted MR images were used to manually segment the head, body and tail of the HC and the AG. HC volumes, cor...

To determine overall patterns of brain atrophy associated with memory, executive function (EF) and dopamine non-responsive motor measures in older parkinsonian patients. Forty-three older PD patients (>or=65 years) and matched controls underwent a neurological examination (Unified Parkinson's Disease Rating Scale, separated into dopamine responsive...

Parkinson disease (PD) is a progressive neurodegenerative disorder in which the major pathologic substrate is a loss of dopaminergic neurons from the lateral substantia nigra pars compacta (SNc). Our objective was to determine whether, in patients with early PD, SNc changes evident on MRI sequences sensitive to iron content corresponded anatomicall...

To determine the sensitivity of positron emission tomography with 11C-labeled dihydrotetrabenazine (DTBZ) to the nigrostriatal changes associated with early, untreated Parkinson's disease (PD), and to determine the correlation between any regionally reduced DTBZ binding and the major motor features of PD. Untreated patients with early PD (n = 27) a...

In replyWe respectfully but strongly disagree with Dr Rosenberg's perception that the 2 cited articles are redundant. We welcome the opportunity to respond to his letter and, in the limited space allowed, explain why the 2 papers are clearly different. While the original article reported the primary efficacy and safety results of the SP 512 Transde...

Excessive Sleepiness in Parkinson's Disease: A Wake-Up Call - Volume 34 Issue 4 - W. R. Wayne Martin

Impaired brain energy metabolism with increased regional brain lactate may play a role in the pathogenesis of Huntington's disease (HD). Magnetic resonance spectroscopy (MRS) has provided conflicting evidence, however, regarding metabolic changes. Our objective was to evaluate the potential contribution of CSF lactate to the changes observed with M...

Unlike traditional, tracer-based methods of molecular imaging, magnetic resonance spectroscopy (MRS) is based on the behavior of specific nuclei within a magnetic field and the general principle that the resonant frequency depends on the nucleus' immediate chemical environment. Most clinical MRS research has concentrated on the metabolites visible...

Recent studies suggest that, for many adult-onset neurological diseases, persons born at a certain time of year are at higher risk of the disease. Small-scale studies have suggested that persons born in the spring may be at higher risk of developing Parkinson's disease (PD) late in life. There have also been suggestions that there are clusters of P...

To assess the response to the rotigotine transdermal system (Neupro; Schwarz Pharma Ltd, Monheim, Germany), a nonergolinic dopamine agonist, in patients with early Parkinson disease. Randomized, double-blind, multicenter, placebo-controlled study. Fifty sites in the United States and Canada. Two hundred seventy-seven patients with early Parkinson d...

The anterior cingulate (AC) gyrus and the presupplementary motor area (pre-SMA) show pathological changes in Parkinson's disease (PD). We examined if PD patients show magnetic resonance spectroscopy (MRS) changes in NAA/Cr in the AC, pre-SMA, or posterior cingulate (PC). Forty-four (27 male, 17 female) healthy nondemented PD patients and 38 control...

The objective of this study is to conduct a dose-finding study of sarizotan in Parkinson's disease (PD) patients with dyskinesia to identify a safe dose and to identify a sensitive dyskinesia rating measure. Sarizotan is a novel compound with full 5-HT(1A) agonist properties and additional high affinity for D(3) and D(4) receptors. An open label st...

OBJECTIVE: To determine if future studies of coenzyme Q10 and GPI-1485 in Parkinson disease (PD) may be warranted. METHODS: We conducted a randomized, double-blind, calibrated futility clinical trial of coenzyme Q10 and GPI-1485 in early untreated PD using placebo data from the DATATOP study to establish the futility threshold. RESULTS: The primary...

Clinical assessment is insensitive to the degree of cerebral involvement in amyotrophic lateral sclerosis (ALS). Regional brain concentrations N-acetylaspartylglutamate (NAA) plus myo-inositol (Ins), as measured by magnetic resonance spectroscopy, are respectively decreased and increased, suggesting that these compounds may provide a biomarker of t...

Objective: To identify the emerging clinical precursors that indicate the early onset of Huntington disease (HD) in a reliable and gene-specific manner. This information is critical for the development of therapeutic trials aimed at postponing clinical onset in HD gene carriers. Methods: Between July 1999 and January 2004, 1001 adults at 50-50 r...

Elevated homocysteine is associated with increased risk of heart disease, stroke, and dementia. Therapy of Parkinson disease (PD) with levodopa elevates homocysteine. The authors conducted a 6-week, multicenter, randomized, double-blind, placebo-controlled trial to test whether folate 1 mg/vitamin B(12) 500 microg or entacapone reduced serum homocy...

The objective of this study was to compare basal ganglia activation in patients with Parkinson's disease to that of healthy controls, using functional MRI (fMRI). Six mildly-affected patients, off antiparkinsonian medications for at least 12h, and seven age-matched controls performed a unilateral motor switching task during fMRI data acquisition. C...

Background: Creatine and minocycline were prioritized for testing in Phase II clinical trials based on a systematic evaluation of potentially disease modifying compounds for Parkinson disease (PD). Objective: To test whether creatine and minocycline alter the course of early PD relative to a predetermined futility threshold for progression of PD in...

A 61-year-old woman with Parkinson's disease, receiving pergolide 1.75 mg four times daily, was admitted with progressive dyspnea. Investigations revealed mitral and aortic regurgitation. She underwent surgical mitral replacement and aortic repair, but had a post-operative course characterized by repeated bouts of congestive heart failure. Severe t...

Background: Motor fluctuations are a common complication in patients with Parkinson disease (PD) receiving long-term levodopa therapy. Slowed gastric emptying and poor solubility of levodopa in the gastrointestinal tract may delay the onset of drug benefit after dosing. Etilevodopa is an ethyl-ester prodrug of levodopa that has greater gastric solu...

Scozzafava J, Takahashi J, Johnston, W, Puttagunta L, Martin W. Valvular Heart Disease in Pergolide-Treated Parkinson’s Disease. CJNS. 2006; 33(1): 111-113.

Introduction In the early days of clinical magnetic resonance imaging (MRI), the exquisite anatomical detail evident in images of the midbrain led investigators to evaluate this new imaging modality in patients with Parkinson's disease (PD). It soon became apparent that the prominent low-signal regions evident in the brainstem and basal ganglia cor...

Freezing of gait (FOG) is common in patients with Parkinson disease (PD) and responds poorly to medical treatment. Botulinum toxin A (BTX-A) injections into calf muscles decreased FOG in previous open-label studies. The authors conducted a randomized double-blind placebo-controlled crossover study of BTX-A vs placebo in 12 subjects with PD and FOG....

At present, conventional magnetic resonance imaging (MRI) shows no convincing structural changes in Parkinson’s disease (PD) itself, but it may be useful in helping to distinguish PD from other neurodegenerative parkinsonian syndromes. Magnetic resonance spectroscopy (MRS) also may provide useful information in distinguishing PD from disorders such...

The serum concentration of the copper protein ceruloplasmin has been an important diagnostic indicator of Wilson's disease (WD). It is widely quoted that 95% of people with WD have low serum ceruloplasmin concentrations. Current evidence suggests that a normal serum ceruloplasmin concentration is more common in patients with WD, particularly those...

Parkinson's disease is a progressive neurodegenerative disorder that demands a holistic approach to treatment. Both pharmacologic and nonpharmacologic interventions play an important role in the comprehensive management of this disorder. While levodopa remains the single most effective medication for symptomatic treatment, dopamine agonists are pla...

Context: Monotherapy with rasagiline mesylate may be useful in early Parkinson disease (PD). Objective: To evaluate the safety and efficacy of the selective monoamine oxidase type B inhibitor rasagiline. Design: Multicenter, 26-week, parallel-group, randomized, double-blind, placebo-controlled clinical trial. Setting: Academically based move...

A multiple-gradient-echo sequence is proposed for accurately mapping R(2)(*) in the presence of in-slice macroscopic susceptibility gradients. In-slice signal loss caused by background macroscopic susceptibility gradients is mitigated by combining three successive gradient-echo images whose slice refocus gradients are successively incremented. The...

Physicians are becoming more astute at diagnosing the various parkinsonian syndromes but in clinical practice it is still often difficult to make the correct diagnosis. This review discusses new evidence that may aid physicians in correctly identifying parkinsonian syndromes. We will review the newest developments in the areas of clinical features,...

Proton magnetic resonance spectroscopy (1H MRS) is used frequently to evaluate normal and pathological states in brain. MRS results are often reported as ratios of peak areas from spectra acquired at a single echo time, primarily for the peaks arising from N-acetyl groups (NA), creatine/phosphocreatine (t-Cr), and choline (Cho). Peak areas, however...

In 1993, the last AAN Practice Parameter on medical treatment of Parkinson's disease (PD) concluded that levodopa was the most effective drug for management of this disorder. Since then, a number of new compounds including non-ergot dopamine agonists (DA) and sustained-release levodopa have been released and studied. Thus, the issue of treatment in...

Somnolence is a recognized adverse effect of dopamine agonists. Two new dopamine agonists, pramipexole and ropinirole, have been reported to cause sudden-onset sleep spells in patients with Parkinson disease (PD) while they were driving. The frequency of these spells and whether driving should be restricted has yet to be established. To determine t...

We studied daytime sleepiness in 160 patients with Parkinson's disease and 40 normal subjects. We compared the prevalence of daytime sleepiness in patients who were taking levodopa alone, levodopa with bromocriptine, levodopa with ropinirole, and levodopa with pramipexole. We found that (1) all these anti-Parkinson drugs can cause daytime sleepines...

Objectives: To determine whether chronic treatment with coenzyme Q(10) or remacemide hydrochloride slows the functional decline of early Huntington's disease (HD). Methods: The authors conducted a multicenter, parallel group, double-blind, 2 X 2 factorial, randomized clinical trial. Research participants with early HD (n = 347) were randomized to r...