Biomedical subjects

Charles H Adler

Publications and source records attributed to Charles H Adler.

At least 19 recordsLinked to original sources

PubMed2026

Dose-dependent white matter changes associated with repetitive head impacts in former American football players.

Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45-74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45-74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen's d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen's d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P < 0.00001) and an earlier age of first exposure to tackle football (P < 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P < 0.04) and rotational force (P < 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.

American football↗

PubMed2026

Regional ventricular enlargement as an in vivo biomarker of cumulative biomechanical neurodegeneration in former American football players.

INTRODUCTION: Repetitive head impacts (RHIs) have been linked to later life neurodegeneration, yet the in vivo structural correlates of cumulative biomechanical loading remain unclear. We examined whether regional ventricular morphology in former American football players reflects exposure burden and traumatic encephalopathy syndrome (TES) classification. METHODS: Participants included 170 male former football players and 54 age-matched asymptomatic male controls from the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Subject-specific manual segmentation quantified lateral ventricle, inferior horn, third ventricle, and fourth ventricle volumes. Group and exposure associations were tested using generalized least squares models. RESULTS: Former players showed larger left inferior lateral ventricle volume than controls, with the largest effects among professional players. Greater cumulative linear and rotational acceleration exposure was associated with enlargement across lateral ventricular and inferior horn regions. DISCUSSION: Regional ventricular enlargement may represent an in vivo marker of cumulative biomechanical loading after RHI exposure.

Humans↗

PubMed2007

Pathogenicity of the Lrrk2 R1514Q substitution in Parkinson's disease.

An increasing number of nonsynonymous LRRK2 variants are being reported as putative pathogenic mutations. We identified one large kindred harboring the Lrrk2 R1514Q substitution; however, the variant did not segregate fully with disease. Combined analyses of three case-control series demonstrate that the R1514Q substitution is not associated with increased risk of disease (OR: 1.3; 95% CI: 0.6-2.8; P = 0.45). These findings highlight the importance of using family-based studies and multiple population screenings when examining the association of these polymorphic LRRK2 gene variants with Parkinson's disease.

Aged↗

PubMed2006

Corticomuscular coherence is increased in the small postural tremor of Parkinson's disease.

The mechanisms and electrophysiological characteristics of the postural tremor in Parkinson's disease (PD) have not been defined. We hypothesized that PD subjects with small amplitude postural tremor would show increased corticomuscular coherence at certain frequencies compared to PD subjects without visible tremor. Four groups of participants were studied: (1) Control without postural tremor, (2) Control with small amplitude postural tremor, (3) PD without postural tremor, and (4) PD with small amplitude postural tremor. Accelerometry and electroencephalography-electromyography fast-fourier transform and corticomuscular coherence spectra were generated. Findings showed (1) elevated corticomuscular coherence centered at 12-18 Hz in PD with small amplitude postural tremor; (2) 5-12 Hz accelerometer frequency peaks that did not shift with increasing weight loads in some individuals; and (3) 5-8 Hz accelerometer peaks that shifted frequency with increasing weight loads, consistent with a peripheral-mechanical oscillator in all groups. The small amplitude postural tremor in PD arises from heterogeneous oscillator mechanisms. The discovery of increased corticomuscular coupling shows cortical involvement in the small amplitude postural tremor of PD.

Aged↗

PubMed2006

Restless legs syndrome in Parkinson's disease patients may improve with subthalamic stimulation.

We report on 6 advanced Parkinson's disease (PD) patients who underwent bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery whose restless legs syndrome (RLS) improved postoperatively. Despite a mean 56% decrease in their levodopa equivalents postoperatively, their RLS scores dropped by a mean of 84% (100% in three). Our findings suggest that bilateral STN DBS surgery can improve RLS in patients with advanced PD.

Aged↗

PubMed2006

Genetics of restless legs syndrome.

Restless legs syndrome (RLS) is a common disorder, although under-diagnosed, with a prevalence of up to 15% depending on the population sampled. Familial aggregation has been widely shown since Ekbom formerly described the condition in 1960; twin studies support a genetic contribution in the development of this disorder. Molecular genetic approaches have identified three genomic regions in RLS susceptibility, however no specific mutations have yet been identified. Herein, we review the current status of genetics in RLS, providing some methodological guidelines to help future research.

Gene Frequency↗

PubMed2005

Sleep issues in Parkinson's disease.

Sleep disturbances in patients with Parkinson's disease (PD) are common, are often severe, and are typically underrecognized and ineffectively treated. After the recognition that some patients with PD could fall asleep unexpectedly when driving, with resulting dangerous consequences, it became evident not only that PD medications might be partly responsible but that there were many additional factors contributing to sleep disturbance in these patients. This review discusses the myriad sleep disorders seen in patients with PD, presents their diagnostic features, and gives recommendations on their management. Effective management of sleep disturbances and excessive daytime sleepiness can greatly improve the quality of life for patients with PD.

Antiparkinson Agents↗

PubMed2005

Parkinsonism, FXTAS, and FMR1 premutations.

The presence of late-onset neurological symptoms in male carriers of premutation expansions of the fragile X mental retardation 1 (FMR1) gene has been described recently. One of the clinical symptoms in this fragile X-associated tremor/ataxia syndrome (FXTAS) is parkinsonism. To test the possible association between expanded FMR1 alleles and Parkinson's disease (PD), we determined the size of the FMR1 CGG repeat in 414 male cases of clinically diagnosed parkinsonism, the majority of whom had PD. None of our patients had expanded FMR1 repeats within the premutation range (55-200 CGG repeats). Five patients (1.2%) carry intermediate-size alleles (41-54 CGG repeats). Expansions within the FMR1 gene are not associated with PD in our study.

Adolescent↗

PubMed2005

Nonmotor complications in Parkinson's disease.

Parkinson's disease (PD) is most often considered a disorder of movement. Whereas bradykinesia, rigidity, tremor, and postural instability result in disability, nonmotor complications in PD may be of equal or greater significance in some patients. This review will discuss many of the nonmotor complications in PD, including cognitive, autonomic, sleep, and sensory difficulties that may occur.

Antidepressive Agents↗

PubMed2005

Parkinson's disease and sleep.

Sleep disorders are common in PD and many factors can contribute to disturbed nocturnal sleep and daytime sleepiness. Factors contributing to sleep disturbance include the presence of insomnia, mood or anxiety disorders, dementia, specific sleep disorders, PD motor disorders, and the effects of PD or medications. Patients who have PD should be interrogated about sleep disturbance and daytime sleepiness and preferably, because of underestimation of the severity of sleepiness or lack of awareness, patients should be interviewed in the presence of a close friend or relative. The ability to drive, if sleepiness is present, should be assessed and appropriate recommendations made. Treatment of sleepiness involves treating any underlying sleep disturbance and may involve the use of stimulant or alerting medications in the daytime.

Aged↗

PubMed2004

Botulinum toxin type A for treating voice tremor.

BACKGROUND: Voice tremor, like spasmodic dysphonia and other tremor disorders, may respond to botulinum toxin type A injections. OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin type A injections as treatment for voice tremor. DESIGN: A randomized study of 3 doses of botulinum toxin type A with 6 weeks of follow-up. SETTING: A single-site tertiary care center. PARTICIPANTS AND METHODS: Thirteen subjects (11 women, 2 men; mean age, 73 years) with voice tremor and no spasmodic dysphonia or head, mouth, jaw, or facial tremor were entered into this study. Patients received 1.25 U (n = 5), 2.5 U (n = 5), or 3.75 U (n = 3) of botulinum toxin type A in each vocal cord. All patients were evaluated at baseline and postinjection at weeks 2, 4, and 6. MAIN OUTCOME MEASURES: The primary outcome measure was the patient tremor rating scale, with secondary measures including patient-rated functional disability, response rating scale, independent randomized tremor ratings, and acoustical measures. RESULTS: All patients at all dose levels noted an effect from the injection. The mean time to onset of effect was 2.3 days (range, 1-7 days). For all patients combined, mean tremor severity scale scores (rated by patients on a 5-point scale) improved 1.4 points at week 2, 1.6 points at week 4, and 1.7 points at week 6. Measures of functional disability, measures of the effect of injection, independent ratings of videotaped speech, and acoustic measures of tremor also showed improvement. The main adverse effects at all doses were breathiness and dysphagia. CONCLUSION: Voice tremor improves following injections of botulinum toxin type A.

Aged↗

PubMed2004

Neuropathology of primary restless leg syndrome: absence of specific tau- and alpha-synuclein pathology.

The neuroanatomical substrate for restless legs syndrome (RLS) is unknown. We identified 4 patients with idiopathic RLS who came to post-mortem examination, where brain and spinal cord tissue were available for neuropathological assessment. Lewy bodies were not identified and alpha-synuclein immunohistochemistry was uniformly negative. Neurofibrillary tangle pathology was variable and nonspecific. These findings suggest that tau- or alpha-synuclein brain pathology is not a component of primary RLS. Although chronic ischemic changes were found in all 4 cases, these were probably incidental. The absence of diagnostic microscopic brain or spinal cord pathology suggests that the pathologic substrate may be neurochemical or receptor based.

Aged↗

PubMed2004

Safety and efficacy of botulinum toxin type B (Myobloc) in adductor spasmodic dysphonia.

This single-site, open-label, dose-finding study evaluated the safety and efficacy of botulinum toxin type B (BoNT-B; Myobloc) for the treatment of adductor spasmodic dysphonia (AdSD) in 13 patients. Three patients received a total of 50 U (25 U per vocal fold); the same three subsequently received 100 U, and then 10 more received 200 U. The primary measure of efficacy was the patient's rating of the change in the severity of spasms on a scale from -3 to +3. There were seven secondary measures of efficacy, including blinded ratings of the sound of voice recorded on audiotape. At Week 8 after injection, spasms improved in 0 of 3 patients who received 50 U, 1 of 3 patients who received 100 U, and 8 of 10 patients who received 200 U. The mean (+/- standard deviation [SD]) score for the change in spasm severity at Week 8 in the 200 U group was 1.4 (+/-1.2) points (P = 0.004). All seven secondary measures also showed improvement. Breathiness was the most common side effect but was mild in intensity and of short duration. We conclude that BoNT-B is safe and effective for the treatment of adductor spasmodic dysphonia.

Adult↗

PubMed2003

Altered aiming movements in Parkinson's disease patients and elderly adults as a function of delays in movement onset.

This study investigated the effect of lengthening the time the hand remains immobilized on an aiming movement performed by Parkinson's disease (PD) patients and elderly adults, and whether visual information could compensate for the effects of delay. In Experiment One, PD patients and elderly adults kept the limb in a static position for 1, 6, or 10 s prior to movement initiation, both with and without vision of the initial limb position and the movement trajectory. Compared to elderly adults, PD patients had increased movement times and jerk scores, and exhibited shorter primary submovements that erred in initial movement direction. Lengthening the time delay increased movement time, decreased mean acceleration, and decreased the distance covered in the primary submovement for both groups. Parkinsonian patients, however, exhibited reduced length of the primary submovement across delay compared to elderly adults. Occluding vision caused the movements of PD patients to deteriorate on all measures. Although the performance of both groups was enhanced when vision was available, vision was not able to fully counteract the effects of delay in either group. In Experiment Two, participants moved to a previously viewed target to examine movement accuracy. Systematic undershooting of the target as a function of delay was found for both groups. Parkinsonian patients exhibited greater undershooting of the target after the primary submovement both with and without vision. Visual feedback reduced the effects of delay for both the elderly and PD patients. It can be inferred from the results that the decay in position sense as a function of time produces impairments in incorporating the initial limb position in motor planning process.

Aged↗

PubMed2003

Randomized trial of modafinil for treating subjective daytime sleepiness in patients with Parkinson's disease.

We assessed the safety and efficacy of modafinil for the treatment of excessive daytime sleepiness in patients with Parkinson's disease (PD). This was a single-site, randomized, double-blind, placebo-controlled crossover study of 21 PD patients having an Epworth Sleepiness Scale (ESS) score > or =10. They received either placebo or modafinil 200 mg/day for 3 weeks, followed by a washout week, then the alternate treatment for 3 weeks. The ESS data demonstrated a carryover effect, so the changes from baseline ESS scores were compared between the two treatments for period 1 only. The ESS scores for the placebo group went from 16.0 +/- 4.2 (mean +/- SD) to 17.0 +/- 5.1 and for the modafinil group went from 17.8 +/- 4.2 to 14.4 +/- 5.7 (P = 0.039). There was no significant carryover effect for any other measure. The patient Clinical Global Impression of Change (+3 to -3) improved by 0.75 on modafinil compared with 0.15 for placebo (P = 0.07). A total of 7 of 20 (35%) of the patients reported some improvement on modafinil but not placebo. There was no significant improvement or worsening of the UPDRS subscores I-III, Timed Tap test, or time on. Vital signs, electrocardiograms, and lab tests were unchanged. Modafinil was very well tolerated. Our data demonstrate that, in a small sample size, administration of 200 mg/day of modafinil was associated with few side effects and was modestly effective for the treatment of excessive daytime sleepiness in patients with PD.

Adult↗

PubMed2003

Abnormal corticomuscular coherence is associated with the small amplitude cortical myoclonus in Parkinson's disease.

Coherence is the degree of time-locked correlation between two signals as a function of frequency. The purpose of this study was to test the following hypotheses: (1) corticomuscular coherence is abnormally increased in those Parkinson's disease (PD) patients with small amplitude cortical myoclonus, and (2) corticomuscular coherence peaks around the time of the myoclonus electromyographic (EMG) discharge. We studied Parkinson's disease patients with and without myoclonus and controls. The data were digitally collected and processed off-line with EMG rectification, creation of 511-msec epochs, Fast-Fourier transform, and coherence analysis. In the 12 to 30 Hz frequency band, but not at 30 to 60 Hz or above, coherence peaks were observed in the PD subjects with myoclonus that were significantly greater than in the control subjects (P < 0.001) and in PD subjects without myoclonus (P < 0.001). The abnormal coherence values are evidence for abnormal rhythmic activity in cortical motor areas in those Parkinson's disease patients with myoclonus. In combination with previous findings on back-averaging, our results show that this myoclonus occurs when neuronal populations are driven to an extreme amount of synchronous activity with higher corticomuscular coherence values. These results have mechanistic implications for cortical dysfunction in Parkinson's disease and for cortical myoclonus in general.

Aged↗

PubMed2003

Time delays prior to movement alter the drawing kinematics of elderly adults.

Position sense has been found to decay as a function of the time delay the limb remains in a static position prior to movement onset. Position sense has also been found to deteriorate as a function of aging, with increased reliance on vision by the elderly. This study investigated whether the pointing kinematics of elderly adults were differentially affected by delay compared to young adults, and whether visual information could compensate for the effects of delay. Young and elderly adults kept the limb in a static position for 1, 6, or 10 s prior to movement onset, both with and without vision of the limb, initial position, and the movement trajectory. Across groups, delay resulted in increased overall movement duration, decreased peak velocity including a shorter relative time to peak velocity, with decreased distance and duration of the primary submovement. Delay and lack of vision differentially decreased distance of the primary submovement for elderly adults. Vision was able to compensate to some degree for the effects of delay across age groups. The findings provide evidence that decays in position sense as a function of time create difficulties in incorporating the initial limb position in motor planning process in elderly adults.

Adult↗

PubMed2003

Case studies in movement disorders.

Six cases representing the most commonly encountered movement disorders-restless legs syndrome with periodic limb movements, tics, myoclonus, chorea, essential tremor, and cervical dystonia-are presented. Discussion of each case focuses on a practical approach to recognizing the important clinical features of each movement disorder as well as the current therapeutic options. A detailed discussion of botulinum toxin follows the case on cervical dystonia, focusing on its mechanism of action, clinical indications, side effects, and dosing.

Adolescent↗