Christopher W. Hess

The temporal pattern of stimulation may be important to the mechanism of deep brain stimulation

Deep brain stimulation (DBS) has emerged as an important and potentially powerful treatment option for the management of carefully selected patients with advanced Parkinsons disease (PD) who are not adequately controlled by standard medication therapy. Though considerable advances have been made, the mechanisms underlying the therapeutic effects of DBS remain unclear despite its clinical efficacy. It is now widely held that both excitation and inhibition can occur secondary to stimulation, and it is suspected that abnormal synchronized oscillations may also be important in the mechanism of DBS. Other potentially important processes, including blood flow changes, local and upstream neurogenesis, and the modulation of neurotransmitters through stimulation of bordering astrocytes are also being investigated. Recent research has suggested that the temporal pattern of DBS stimulation is also an important variable in DBS neuromodulation, yet the extent of its influence on DBS efficacy has yet to be determined. As high stimulation frequency alone does not appear to be sufficient for optimal symptom suppression, attention to stimulation pattern might lead to more effective symptom control and reduced side effects, possibly at a lower frequency. Stimulation pattern may be potentially amenable to therapeutic modulation and its role in the clinical efficacy of DBS should be addressed through further focus and research.

Tremor: Clinical Phenomenology and Assessment Techniques

Background Tremors are among the most common movement disorders. As there can be considerable variability in the manner in which clinicians assess tremor, objective quantitative tools such as electromyography, accelerometry, and computerized, spiral analysis can be very useful in establishing a clinical diagnosis and in research settings. Methods In this review, we discuss the various methods of quantitative tremor analysis and the classification and pathogenesis of tremor. The most common pathologic tremors and an approach to the diagnosis of tremor etiology are described. Conclusions Pathologic tremors are common, and the diagnosis of underlying etiology is not always straightforward. Computerized quantitative tremor analysis is a valuable adjunct to careful clinical evaluation in distinguishing tremulous diseases from physiologic tremors, and can also help shed light on their pathogenesis.

Weight Loss and Impact on Quality of Life in Parkinson’s Disease

Introduction Weight loss is common in Parkinson’s Disease (PD) and sometimes may precede the diagnosis. Weight loss is associated with multiple factors but its impact on health-related quality of life (HRQL) in PD remains unknown. We sought to investigate the factors associated with weight change and to quantify its effect on HRQL. Methods The National Parkinson Foundation Quality Improvement Initiative (NPF-QII) data was used to analyze PD patients longitudinally between two visits, separated by 12±6 months. Multiple linear regression analyses were used to assess the associations between baseline covariates and body weight change per month, and to evaluate whether, and to what degree, Parkinson’s Disease Questionnaire (PDQ-39) scores were affected. Results A higher Hoehn & Yahr stage, higher number of comorbidities, older age, lower MOCA estimate, and higher rate of levodopa usage were observed in patients who lost weight. Multivariate regression analysis indicated that age and levodopa usage were significantly associated with weight loss. Furthermore, monthly body weight loss was significantly associated with HRQL decline in PD patients. Loss of 1 lb (0.45 kg) per month was associated with a decline in QOL: an increase of 0.5% in PDQ-39 Summary Index score (p=0.004), and 1.1% and 1.5% increases in the mobility and ADL dimensions, respectively. Conclusion Weight loss in PD is common and seems to correlate with worsened HRQL. Awareness of factors associated with weight loss and its relation to HRQL may help practitioners improve patient management and expectations.

Randomized, Blinded Pilot Testing of Nonconventional Stimulation Patterns and Shapes in Parkinson's Disease and Essential Tremor: Evidence for Further Evaluating Narrow and Biphasic Pulses

Evidence suggests that nonconventional programming may improve deep brain stimulation (DBS) therapy for movement disorders. The primary objective was to assess feasibility of testing the tolerability of several nonconventional settings in Parkinsons disease (PD) and essential tremor (ET) subjects in a single office visit. Secondary objectives were to explore for potential efficacy signals and to assess the energy demand on the implantable pulse‐generators (IPGs).

Increased variability in spiral drawing in patients with functional (psychogenic) tremor

Increased variability is a characteristic clinical and physiologic feature of functional (psychogenic) tremor. In this study, we use computerized spiral analysis to show that the variability of a motor task is a quantifiable characteristic of functional tremor. We compare functional tremor patients to phenomenologically similar dystonic tremor patients and to normal controls. We used the spiral severity score, a measure that does not incorporate spiral tightness, as a marker of spiral drawing performance, and inter-spiral tightness variability (based on the 25-75%(ile) range in tightness across ten spirals) to evaluate the effects of functional tremor on drawing spirals. The spirals of 74 participants: 22 functional tremor, 21 dystonic tremor, and 31 normal controls were analyzed. Spiral severity was higher in both tremor groups compared to controls, but did not differentiate them. Inter-spiral variability, however, was higher in the functional tremor group compared to both other groups. Thus, spiral analysis captures variability of a motor task and may be used as an objective test for functional tremor. The effect of functional tremor in other motor tasks should be investigated.

Oculomotor nerve palsy as the presenting symptom of gummatous neurosyphilis and human immunodeficiency virus infection: clinical response to treatment.

A39-year-oldmanpresentedwith5monthsofworseningrighteyelid ptosis, fatigue, and diplopia, which progressed to include anorexia, low-grade fevers, and arthralgias. An examination revealed a subtlemacular rashonhis trunk,arms,andpalms.Therightpupilwas dilated to 5mmwithout direct or consensual response to light or accommodationwith inferotemporal deviation of the eye. Extraocular movements were impaired in all directions except abduction, with near-complete ptosis of the eyelid. Serumstudies showedapositive rapidplasmareagintestresult (to1:64)andreactivefluorescenttreponemal antibodies and Lyme antibodies. Cerebrospinal fluid analysis demonstratedatotalprotein levelof0.084g/dL(toconvert tograms per liter,multiply by 10.0); a glucose level of 47mg/dL (to convert to millimolesper liter,multiplyby0.055);awhitebloodcellcountof18/μL (to convert to ×109 per liter,multiply by0.001); red blood cell count of 3 × 106/μL (to convert to×1012 per liter,multiply by 1.0); 91% lymphocytes; 9% monocytes; a polymerase chain reaction test result negative for Lymedisease; and aVenereal DiseaseResearch Laboratory test result reactive to 1:2. Subsequent human immunodeficiencyvirus (HIV)antibodyandWesternBlot testswerepositivewith a CD4 lymphocyte count of 307 and a viral load of 30 000. Magnetic resonance imaging of his brain revealed an enlarged enhancing right third cranial nerve in the interpeduncular cistern. A focus of fluid-attenuated inversion recovery hyperintensity and enhancement was also noted in the right temporal lobe cortex (Figure 1). Neurosyphilis was diagnosed, and he was treated with a 2-week course of intravenous penicillin (24 million units daily).

Modulation of cortical-subcortical networks in Parkinson's disease by applied field effects.

Studies suggest that endogenous field effects may play a role in neuronal oscillations and communication. Non-invasive transcranial electrical stimulation with low-intensity currents can also have direct effects on the underlying cortex as well as distant network effects. While Parkinson’s disease (PD) is amenable to invasive neuromodulation in the basal ganglia by deep brain stimulation (DBS), techniques of non-invasive neuromodulation like transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) are being investigated as possible therapies. tDCS and tACS have the potential to influence the abnormal cortical-subcortical network activity that occurs in PD through sub-threshold changes in cortical excitability or through entrainment or disruption of ongoing rhythmic cortical activity. This may allow for the targeting of specific features of the disease involving abnormal oscillatory activity, as well as the enhancement of potential cortical compensation for basal ganglia dysfunction and modulation of cortical plasticity in neurorehabilitation. However, little is currently known about how cortical stimulation will affect subcortical structures, the size of any effect, and the factors of stimulation that will influence these effects.

Functional activity of the sensorimotor cortex and cerebellum relates to cervical dystonia symptoms

Cervical dystonia (CD) is the most common type of focal dystonia, causing abnormal movements of the neck and head. In this study, we used noninvasive imaging to investigate the motor system of patients with CD and uncover the neural correlates of dystonic symptoms. Furthermore, we examined whether a commonly prescribed anticholinergic medication in CD has an effect on the dystonia‐related brain abnormalities. Participants included 16 patients with CD and 16 healthy age‐matched controls. We collected functional MRI scans during a force task previously shown to extensively engage the motor system, and diffusion and T1‐weighted MRI scans from which we calculated free‐water and brain tissue densities. The dystonia group was also scanned ca. 2 h after a 2‐mg dose of trihexyphenidyl. Severity of dystonia was assessed pre‐ and post‐drug using the Burke–Fahn–Marsden Dystonia Rating Scale. Motor‐related activity in CD was altered relative to controls in the primary somatosensory cortex, cerebellum, dorsal premotor and posterior parietal cortices, and occipital cortex. Most importantly, a regression model showed that increased severity of symptoms was associated with decreased functional activity of the somatosensory cortex and increased activity of the cerebellum. Structural imaging measures did not differ between CD and controls. The single dose of trihexyphenidyl altered the fMRI signal in the somatosensory cortex but not in the cerebellum. Symptom severity was not significantly reduced post‐treatment. Findings show widespread changes in functional brain activity in CD and most importantly that dystonic symptoms relate to disrupted activity in the somatosensory cortex and cerebellum. Hum Brain Mapp 38:4563–4573, 2017.

Beta-band activity and connectivity in sensorimotor and parietal cortex are important for accurate motor performance.

ABSTRACT Accurate motor performance may depend on the scaling of distinct oscillatory activity within the motor cortex and effective neural communication between the motor cortex and other brain areas. Oscillatory activity within the beta‐band (13–30 Hz) has been suggested to provide distinct functional roles for attention and sensorimotor control, yet it remains unclear how beta‐band and other oscillatory activity within and between cortical regions is coordinated to enhance motor performance. We explore this open issue by simultaneously measuring high‐density cortical activity and elbow flexor and extensor neuromuscular activity during ballistic movements, and manipulating error using high and low visual gain across three target distances. Compared with low visual gain, high visual gain decreased movement errors at each distance. Group analyses in 3D source‐space revealed increased theta‐, alpha‐, and beta‐band desynchronization of the contralateral motor cortex and medial parietal cortex in high visual gain conditions and this corresponded to reduced movement error. Dynamic causal modeling was used to compute connectivity between motor cortex and parietal cortex. Analyses revealed that gain affected the directionally‐specific connectivity across broadband frequencies from parietal to sensorimotor cortex but not from sensorimotor cortex to parietal cortex. These new findings provide support for the interpretation that broad‐band oscillations in theta, alpha, and beta frequency bands within sensorimotor and parietal cortex coordinate to facilitate accurate upper limb movement. Summary statement: Our findings establish a link between sensorimotor oscillations in the context of online motor performance in common source space across subjects. Specifically, the extent and distinct role of medial parietal cortex to sensorimotor beta connectivity and local domain broadband activity combine in a time and frequency manner to assist ballistic movements. These findings can serve as a model to examine whether similar source space EEG dynamics exhibit different time‐frequency changes in individuals with neurological disorders that cause movement errors. HIGHLIGHTSCortical activity and connectivity were examined during upper limb movement.Visual feedback gain led to better motor performance and increased muscle activity.Increased theta‐, alpha‐, and beta‐band desynchronization at high gain feedback.Increased parietal‐to‐motor cortex connectivity in the beta‐band at high gain feedback.Visual gain did not affect motor‐to‐parietal cortex connectivity.

The Evolving Role of Diffusion Magnetic Resonance Imaging in Movement Disorders

Significant advances have allowed diffusion magnetic resonance imaging (MRI) to evolve into a powerful tool in the field of movement disorders that can be used to study disease states and connectivity between brain regions. Diffusion MRI is a promising potential biomarker for Parkinson’s disease and other forms of parkinsonism, and may allow the distinction of different forms of parkinsonism. Techniques such as tractography have contributed to our current thinking regarding the pathophysiology of dystonia and possible mechanisms of penetrance. Diffusion MRI measures could potentially assist in monitoring disease progression in Huntington’s disease, and in uncovering the nature of the processes and structures involved the development of essential tremor. The ability to represent structural connectivity in vivo also makes diffusion MRI an ideal adjunctive tool for the surgical treatment of movement disorders. We review recent studies using diffusion MRI in movement disorders research and present the current state of the science as well as future directions.