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Anthony E Lang

Publications and source records attributed to Anthony E Lang.

At least 19 recordsLinked to original sources
PubMed2007

Punding prevalence in Parkinson's disease.

The purpose of this study was to determine punding prevalence in an ambulatory Parkinson's disease (PD) population. We conducted a patient-and-caregiver-completed punding survey in 373 consecutive patients in an academic ambulatory center. Completion rate was 78%. Only four patients were identified as punding. Patients did not retain insight to their behavior. Forty patients with high-dose levodopa monotherapy or levodopa and dopamine agonist treatment had physician-administered interview. None had punding. Punding incidence was low in this patient group (1.4%) in contrast with previous reports of 14%. Despite the low incidence, this behavior is disruptive and should be carefully elicited by physicians caring for Parkinson's disease patients.

Aged↗
PubMed2007

Antipsychotic use in older adults with Parkinson's disease.

The choice of agents to treat psychotic symptoms in Parkinson's disease is important given the potential for antipsychotics to worsen Parkinsonism. The purpose of this study was to estimate the incidence of psychotic symptoms requiring treatment in individuals with Parkinson's disease after starting dopaminergic medications, and to describe the agents being selected as initial antipsychotic therapy. Using the administrative health care databases of Ontario, Canada, individuals 66 years of age or older with Parkinson's disease who were newly treated with dopaminergic agents were identified. Subsequent prescriptions for antipsychotic medications were then identified. A total of 10,347 older adults were newly started on dopaminergic agents between 1998 and 2003. The Kaplan-Meier estimate for the cumulative probability of requiring an antipsychotic at 7 years was 35%; 499 individuals (4.8%; 5.2/100 person-years) were prescribed an antipsychotic within 1 year of starting dopaminergic therapy. The proportion of initial antipsychotic prescriptions for typical antipsychotics decreased from 56% (42 of 75) in 1998 to 9% (8 of 88) in 2002. Antipsychotic use is common in individuals with Parkinsonism newly treated with dopaminergic medication. Typical antipsychotics are still commonly being chosen as first-line agents for older patients, indicating a need for interventions to improve practice.

Aged↗
PubMed2007

Unilateral versus bilateral tasks in early asymmetric Parkinson's disease: differential effects on bradykinesia.

Patients with Parkinson's disease (PD) have an impaired ability to perform two different simultaneous bimanual tasks. The differential effects of unilateral versus bilateral identical tasks on the bradykinesia scores of the more and less affected limbs in PD have not been examined. Twenty-seven patients with early and asymmetric PD underwent blinded, videotaped assessment, independently for each limb, using the bradykinesia items of the Unified Parkinson's Disease Rating Part III, Motor subscale (mUPDRS) and a Modified Bradykinesia Rating Scale (MBRS), which assessed amplitude, speed, and rhythm of movements. We found that the score for finger tapping in mUPDRS and MBRS, the score of amplitude of finger tapping in MBRS, and the lateralized scores of mUPDRS (sum of Items 23 to 25) of the most affected side significantly improved during the bimanual task. The improvement was associated with longer duration of illness, higher total scores in mUPDRS, and higher lateralized bradykinesia scores of the most affected side. There was a simultaneous deterioration of the lateralized bradykinesia scores in MBRS (sum of Items 23 to 25) and Item 25 of mUPDRS (rapid alternating movements) of the least affected side in bimanual tasks. In conclusion, identical bimanual tasks facilitate movement of the most affected side in early asymmetric PD at the cost of motor degradation in the least affected side. This observation also highlights the need to perform tasks of bradykinesia in one limb at a time for best accuracy.

Aged↗
PubMed2007

Gait abnormalities in psychogenic movement disorders.

An abnormal gait is not uncommon in patients with medically unexplained neurological symptoms, including those with other psychogenic movement disorders (PMDs). Previous studies have not evaluated the gait characteristics of patients with a variety of PMDs and there are no reports comparing PMDs with and without gait disturbances. We were interested in determining how those with and without additional involvement of gait differed and how PMD patients differed from those with a pure psychogenic gait disorder (PGD) in the absence of another PMD. We investigated gait features in a large series of patients with PMD (n = 279), dividing them into two groups (Group I with a normal gait and Group II with an abnormal gait). Group I included those with PMD with a normal gait and no change in the PMD while walking (I-1), and those with a change in PMD while walking, but not affecting gait (I-2). Group II was divided into those with PMD with additional abnormal gait (II-1) and those with pure psychogenic gait disorder without other abnormal movements (II-2). Excessive slowing of movement was more common in PMD patients with an abnormal gait (Group II) compared to those without (Group I). Slowness of gait was the most common feature in patients with PMD combined with a PGD (II-1) and buckling of the knee pattern was the most common type of pure PGD (II-2), followed by astasia-abasia.

Adolescent↗
PubMed2007

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.

Disability Evaluation↗
PubMed2006

Beta oscillatory activity in the subthalamic nucleus and its relation to dopaminergic response in Parkinson's disease.

Recent studies suggest that beta (15-30 Hz) oscillatory activity in the subthalamic nucleus (STN) is dramatically increased in Parkinson's disease (PD) and may interfere with movement execution. Dopaminergic medications decrease beta activity and deep brain stimulation (DBS) in the STN may alleviate PD symptoms by disrupting this oscillatory activity. Depth recordings from PD patients have demonstrated beta oscillatory neuronal and local field potential (LFP) activity in STN, although its prevalence and relationship to neuronal activity are unclear. In this study, we recorded both LFP and neuronal spike activity from the STN in 14 PD patients during functional neurosurgery. Of 200 single- and multiunit recordings 56 showed significant oscillatory activity at about 26 Hz and 89% of these were coherent with the simultaneously recorded LFP. The incidence of neuronal beta oscillatory activity was significantly higher in the dorsal STN (P = 0.01) and corresponds to the significantly increased LFP beta power recorded in the same region. Of particular interest was a significant positive correlation between the incidence of oscillatory neurons and the patient's benefit from dopaminergic medications, but not with baseline motor deficits off medication. These findings suggest that the degree of neuronal beta oscillatory activity is related to the magnitude of the response of the basal ganglia to dopaminergic agents rather than directly to the motor symptoms of PD. The study also suggests that LFP beta oscillatory activity is generated largely within the dorsal portion of the STN and can produce synchronous oscillatory activity of the local neuronal population.

Aged↗
PubMed2006

Subthalamic nucleus stimulation: improvements in outcome with reprogramming.

BACKGROUND: Deep brain stimulation (DBS) is currently the most effective surgical treatment for advanced Parkinson disease (PD). Even when the electrode is well positioned in the target, the optimization of clinical results depends on careful programming of electrical parameters and changes in antiparkinsonian drug dosages. OBJECTIVE: To determine whether stable outcomes from subthalamic nucleus DBS for PD can be improved by revising stimulation parameters and drug dosages through "hands-on" involvement of a neurologist expert in both movement disorders and DBS programming. METHODS: In 44 consecutive patients with PD with long-term stable response to subthalamic nucleus DBS (mean +/- SD, 3.5 +/- 1.7 years), we compared scores from the Unified Parkinson's Disease Rating Scale parts II through IV obtained immediately before and following a formal reprogramming of their stimulation. The reprogramming was performed by a neurologist expert in both PD and DBS and accompanied by further medication adjustments. The patients were subsequently followed up for as long as 14 months. RESULTS: In 24 patients (54.6%), the scores on the Unified Parkinson's Disease Rating Scale parts II and III significantly improved by 15.0% and 25.9%, respectively. Anti-PD drugs were significantly reduced (by 25.9%). No improvement was observed in 16 patients (36.4%), and the conditions of 4 patients (9.1%) worsened. CONCLUSIONS: Further improvement of parkinsonian signs can be achieved in the majority of patients even after long-term stable stimulation. Improved patient outcomes from subthalamic nucleus DBS are obtained when postoperative care is personally managed by a neurologist expert in movement disorders and DBS who is directly responsible for stimulation programming and simultaneous drug adjustments based on observed clinical responses to changing stimulation parameters.

Antiparkinson Agents↗
PubMed2006

Potential early markers of Parkinson disease in idiopathic REM sleep behavior disorder.

BACKGROUND: Idiopathic REM sleep behavior disorder (RBD) is characterized by loss of atonia during REM sleep, resulting in motor activity during dreams. Studies estimate that approximately half of patients with RBD will eventually develop Parkinson disease (PD), so RBD may be an indicator of presymptomatic PD. Several potential early diagnostic markers of PD have been proposed, but they have generally not been tested in presymptomatic PD. The authors hypothesized that these markers may be abnormal in idiopathic RBD. METHODS: The authors compared 25 patients with polysomnography-confirmed RBD without PD with age- and sex-matched controls. Color vision, olfaction, quantitative motor testing, and indices of depression, personality, and autonomic function were examined. RESULTS: Patients demonstrated significant impairment in color discrimination and olfactory function. Patients had subtle abnormalities on quantitative testing of motor and gait speed. Autonomic symptoms were more common in patients than controls. Abnormalities were heterogeneous, with some patients scoring normally on all domains, whereas others were severely impaired on multiple domains. Dysfunction on tests of olfactory function, color vision, and motor speed were highly correlated, such that patients who performed poorly on one test tended to perform poorly on the others. CONCLUSIONS: Many potential early markers of Parkinson disease are significantly abnormal in idiopathic REM sleep behavior disorder. These abnormalities are present in approximately half of the patients, suggesting a heterogenous pathophysiology.

Adult↗
PubMed2006

Motor cortex plasticity in Parkinson's disease and levodopa-induced dyskinesias.

Experimental models of Parkinson's disease have demonstrated abnormal synaptic plasticity in the corticostriatal system, possibly related to the development of levodopa-induced dyskinesias (LID). We tested the hypothesis that LID in Parkinson's disease is associated with aberrant plasticity in the human motor cortex (M1). We employed the paired associative stimulation (PAS) protocol, an experimental intervention involving transcranial magnetic stimulation (TMS) and median nerve stimulation capable of producing long-term potentiation (LTP) like changes in the sensorimotor system in humans. We studied the more affected side of 16 moderately affected patients with Parkinson's disease (9 dyskinetic, 7 non-dyskinetic) and the dominant side of 9 age-matched healthy controls. Motor-evoked potential (MEP) amplitudes and cortical silent period (CSP) duration were measured at baseline before PAS and for up to 60 min (T0, T30 and T60) after PAS in abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. PAS significantly increased MEP size in controls (+74.8% of baseline at T30) but not in patients off medication (T30: +0.07% of baseline in the non-dyskinetic, +27% in the dyskinetic group). Levodopa restored the potentiation of MEP amplitudes by PAS in the non-dyskinetic group (T30: +64.9% of baseline MEP) but not in the dyskinetic group (T30: -9.2% of baseline). PAS prolonged CSP duration in controls. There was a trend towards prolongation of CSP in the non-dyskinetic group off medications but not in the dyskinetic group. Levodopa did not restore CSP prolongation by PAS in the dyskinetic group. Our findings suggest that LTP-like plasticity is deficient in Parkinson's disease off medications and is restored by levodopa in non-dyskinetic but not in dyskinetic patients. Abnormal synaptic plasticity in the motor cortex may play a role in the development of LID.

Aged↗
PubMed2006

Childhood onset in familial prion disease with a novel mutation in the PRNP gene.

BACKGROUND: Up to 15% of cases of prion diseases are due to the autosomal dominant inheritance of coding PRNP mutations. OBJECTIVE: To describe the unique clinical and genetic findings in a family of East Indian origin with autosomal dominant inheritance of a novel PRNP mutation. DESIGN: Detailed neurological examination and sequencing analysis of the MAPT and PRNP genes. SETTING: Toronto Western Hospital, Toronto, Ontario. PATIENTS: Five available members of a family of East Indian origin with a rapidly progressive neurodegenerative disorder characterized by dementia, motor decline, and ataxia. RESULTS: We identified a novel Pro105Thr mutation in the PRNP gene in all of the 3 clinically affected family members but not in their unaffected relatives or normal controls. Although 5 of 6 affected family members had a relatively homogeneous phenotype and age at onset (range, 33-41 years), 1 of the 6 patients developed the disease at age 13 years. CONCLUSIONS: A novel mutation in the PRNP gene was identified in all of the available, clinically affected members of this family with a rapidly progressive neurodegenerative disease. To our knowledge, the propositus represents the youngest individual with inherited prion disease described to date.

Adolescent↗
PubMed2006

Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease.

OBJECTIVE: Glial cell line-derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open-label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). METHODS: Thirty-four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15 microg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and (18)F-dopa uptake. RESULTS: At 6 months, mean percentage changes in "off" UPDRS motor score were -10.0% and -4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, -23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean (18)F-dopa influx constant (p = 0.019) was observed. Serious, device-related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on-study and two in the open-label extension). INTERPRETATION: Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased (18)F-dopa uptake. It is uncertain whether technical differences between this trial and positive open-label studies contributed in any way this negative outcome.

Adult↗
PubMed2006

Interface between tauopathies and synucleinopathies: a tale of two proteins.

Neurodegenerative diseases are often classified based on the abnormal accumulation of synuclein or tau. Traditionally, these disorders have been viewed as distinct clinical and pathological entities. However, advances in molecular genetics and protein biochemistry have shown intriguing overlaps. The most common synucleinopathy, Parkinson's disease, is characterized by extrapyramidal motor dysfunction, whereas the most common tauopathy, Alzheimer's disease, is defined by dementia. Yet there is overlap of clinical features; Parkinson's disease patients frequently have dementia, and Alzheimer's disease patients often manifest parkinsonism. Dementia with Lewy bodies exemplifies the existence of a continuum among these diseases. This overlap extends to the neuropathological findings; the pathognomonic hallmark for one set of disorders, Lewy bodies or neurofibrillary tangles, is present more often than expected in the other set. Moreover, mutations in LRRK2 known to cause parkinsonism are associated not only with dopaminergic neuronal degeneration, but also with the accumulation of synuclein, tau, neither, or both proteins. Other shared genetic features between tauopathies and synucleinopathies also exist. Finally, the known protein interactions between tau and synuclein further highlight the interface. Evidence for the intersection of tauopathies and synucleinopathies indicates the need for an updated disease classification scheme and may have important implications for therapeutic development.

Animals↗
PubMed2006

Cortical and spinal abnormalities in psychogenic dystonia.

OBJECTIVE: The pathophysiology of psychogenic dystonia has not been examined, but a growing body of literature suggests that abnormal sensory input from repetitive movements can lead to plastic cortical changes. Reduced cortical and spinal inhibition is well documented in organic dystonia. We tested the hypothesis that aberrant sensory input associated with abnormal posture may cause similar abnormalities by testing patients with psychogenic dystonia. METHODS: We assessed cortical and spinal inhibitory circuits and cortical activity associated with voluntary movement in 10 patients with clinically definite psychogenic dystonia, 8 patients with organic dystonia, and 12 age-matched healthy control subjects. RESULTS: Three measures of cortical inhibition, resting short- and long-interval intracortical inhibition and cortical silent period, were reduced in both psychogenic dystonia and organic dystonia. Cutaneous silent period mediated by spinal circuitries was increased in psychogenic and organic dystonia. Forearm spinal reciprocal inhibition was reduced in psychogenic dystonia. INTERPRETATION: Psychogenic and organic dystonia share similar physiological abnormalities. Previous findings of abnormal cortical and spinal excitability in organic dystonia may, in part, be a consequence rather than a cause of dystonia. Alternatively, these findings may represent endophenotypic abnormalities that predispose to both types of dystonia.

Adult↗
PubMed2006

Homozygous and heterozygous PINK1 mutations: considerations for diagnosis and care of Parkinson's disease patients.

The first mutations described in PINK1 were homozygous. More recently, heterozygous mutations have been reported but the role of heterozygosity in disease pathogenesis is still debated. We describe two unrelated cases with PINK1 mutations (homozygous nonsense and heterozygous missense) that highlight issues regarding the role of heterozygous mutations and the utility of genetic screening in patient care.

Adult↗
PubMed2006

Crossroads in GDNF therapy for Parkinson's disease.

The development of a neuroprotective or neuroregenerative therapy for Parkinson's disease (PD) would be a major therapeutic advance. Unfortunately, results from a recent controlled clinical study delivering the neurotrophic factor, glial-derived neurotrophic factor (GDNF), directly into brain did not demonstrate efficacy and safety of such a treatment. A critical review of available data suggests that there are questions that need to be answered before the future of GDNF as a therapy for PD can be determined.

Animals↗
PubMed2006

Translation of nondopaminergic treatments for levodopa-induced dyskinesia from MPTP-lesioned nonhuman primates to phase IIa clinical studies: keys to success and roads to failure.

Studies in MPTP-lesioned nonhuman primates have demonstrated the potential of nondopaminergic drugs in reducing the problems of levodopa-induced dyskinesia (LID). Here we review the process of translating findings from the monkey to man. Agents targeting glutamate, adensosine, noradrenaline, 5-hydroxytryptamine, cannabinoid, and opioid transmitter systems have been assessed for antidyskinetic potential in human studies. Eleven nondopaminergic drugs with antidyskinetic efficacy in the MPTP primate have been advanced to proof-of-concept phase IIa trials in PD patients (amantadine, istradefylline, idazoxan, fipamezole, sarizotan, quetiapine, clozapine, nabilone, rimonabant, naloxone, and naltrexone). For all six nondopaminergic transmitter systems reviewed, the MPTP-lesioned primate correctly predicted phase II efficacy of at least one drug. Of the 11 specific molecules tested in both monkeys and humans, 8 showed clear antidyskinetic properties in both human and monkey. In the instances where the primate studies did not, or did not consistently, predict the outcome of the human studies, the discrepancy may reflect limitations in the validity of the model or limitations in the design of either the clinical or the preclinical studies. We find that the major determinant of success in predicting efficacy is to ensure that primate studies are conducted in a statistically rigorous way and incorporate designs and outcome measures with clinical applicability. On the other hand, phase IIa trials should strive to replicate the preclinical study, especially in terms of protocol, drug dose equivalence, and outcome measure, so as to test the same hypothesis. Failure to meet these criteria carries the risk of false negative conclusions in phase IIa trials.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2006

Deep brain stimulation: preoperative issues.

Numerous factors need to be taken into account in deciding whether a patient with Parkinson's disease (PD) is a candidate for deep brain stimulation. Patient-related personal factors including age and the presence of other comorbid disorders need to be considered. Neuropsychological and neuropsychiatric concerns relate both to the presurgical status of the patient and to the potential for surgery to result in new problems postoperatively. A number of factors related to the underlying PD need to be considered, including the specific parkinsonian motor indications (e.g., tremor, bradykinesia, gait dysfunction), previous medical therapies, including benefit from current therapy and adverse effects, and past surgical treatments. Definable causes of Parkinsonism, particularly atypical Parkinsonisms, should be considered. Finally, methods of evaluating outcomes should be defined and formalized. This is a report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society (MDS). The report has been endorsed by the Scientific Issues Committee of the MDS and the American Society of Stereotactic and Functional Neurosurgery. It outlines answers to a series of questions developed to address all aspects of deep brain stimulation preoperative decision-making.

Brain↗