Effect of Directional Deep Brain Stimulation on Sensory Thresholds in Parkinson's Disease.

OBJECTIVE: Previous studies showed that deep brain stimulation (DBS) relieves pain symptoms in Parkinson disease (PD) patients when programmed for motor-symptom relief. One factor involved in pain processing is sensory perception of stimuli. With the advent of directional leads, we explore whether directional DBS affects quantitative sensory testing (QST) metrics acutely. METHODS: PD patients with subthalamic (STN) DBS and directional leads were tested in 5 settings (DBS-OFF, DBS-ON with omnidirectional stimulation, and DBS-ON) for each of three directional segments of contact used for clinical programming. The Unified Parkinson's Disease Rating Scale (UPDRS-III) assessed patient's motor skills at time of study visit at clinical contact and at contact which produced optimal sensory threshold (defined by the greatest tolerance to mechanical stimuli). Correlation analyses were performed between stimulation parameters [amplitude, frequency, pulse width (PW), total electrical energy delivered (TEED)] and outcome metrics. RESULTS: Sensory thresholds were obtained in nine patients. Directional stimulation did not significantly alter patient perceptions of sensory stimulus [cold pain (p = 0.69), warm pain (p = 0.99), Von frey fibers (p = 0.09), pin-prick (p = 0.88), vibration (p = 0.40), pressure (p = 0.98)]. With correlation analysis, increasing PW at the posterior contact increased pin prick and vibration sensitivity (p < 0.001). Additionally, an increase in TEED caused a decrease in sensitivity to warm detection when using the anterior (p = 0.04), lateral (p = 0.02), and medial contacts (p = 0.03), and also caused a decrease in sensitivity to cold detection when using the medial contact (p = 0.03). UPDRS-III remained stable during testing. CONCLUSION: Motor benefit can be acutely maintained at directional contacts, whereas directional stimulation can modulate thermal and mechanical sensitivity. Further investigation will determine whether these changes are maintained chronically or can be improved with optimized programming.

Outcome Trends after US Military Concussive Traumatic Brain Injury.

Care for US military personnel with combat-related concussive traumatic brain injury (TBI) has substantially changed in recent years, yet trends in clinical outcomes remain largely unknown. Our prospective longitudinal studies of US military personnel with concussive TBI from 2008-2013 at Landstuhl Regional Medical Center in Germany and twp sites in Afghanistan provided an opportunity to assess for changes in outcomes over time and analyze correlates of overall disability. We enrolled 321 active-duty US military personnel who sustained concussive TBI in theater and 254 military controls. We prospectively assessed clinical outcomes 6-12 months later in 199 with concussive TBI and 148 controls. Global disability, neurobehavioral impairment, depression severity, and post-traumatic stress disorder (PTSD) severity were worse in concussive TBI groups in comparison with controls in all cohorts. Global disability primarily reflected a combination of work-related and nonwork-related disability. There was a modest but statistically significant trend toward less PTSD in later cohorts. Specifically, there was a decrease of 5.9 points of 136 possible on the Clinician Administered PTSD Scale (-4.3%) per year (95% confidence interval, 2.8-9.0 points, p = 0.0037 linear regression, p = 0.03 including covariates in generalized linear model). No other significant trends in outcomes were found. Global disability was more common in those with TBI, those evacuated from theater, and those with more severe depression and PTSD. Disability was not significantly related to neuropsychological performance, age, education, self-reported sleep deprivation, injury mechanism, or date of enrollment. Thus, across multiple cohorts of US military personnel with combat-related concussion, 6-12 month outcomes have improved only modestly and are often poor. Future focus on early depression and PTSD after concussive TBI appears warranted. Adverse outcomes are incompletely explained, however, and additional studies with prospective collection of data on acute injury severity and polytrauma, as well as reduced attrition before follow-up will be required to fully address the root causes of persistent disability after wartime injury.

Comparison of baseline-referenced versus norm-referenced analytical approaches for in-theatre assessment of mild traumatic brain injury neurocognitive impairment.

PRIMARY OBJECTIVE: To examine differences between the baseline-referenced and norm-referenced approaches for determining decrements in Automated Neuropsychological Assessment Metrics Version 4 TBI-MIL (ANAM) performance following mild traumatic brain injury (mTBI). RESEARCH DESIGN: ANAM data were reviewed for 616 US Service members, with 528 of this sample having experienced an mTBI and 88 were controls. METHODS AND PROCEDURES: Post-injury change scores were calculated for each sub-test: (1) normative change score = in-theater score - normative mean and (2) baseline change score = in-theater score - pre-deployment baseline. Reliable change cut-scores were applied to the change and the resulting frequency distributions were compared using McNemar tests. Receiver operator curves (ROC) using both samples (i.e. mTBI and control) were calculated for the change scores for each approach to determine the discriminate ability of the ANAM. MAIN OUTCOMES AND RESULTS: There were no statistical differences, p < 0.05 (Bonferonni-Holm corrected), between the approaches. When the area under the curve for the ROCs were averaged across sub-tests, there were no significant differences between either the norm-referenced (0.65) or baseline-referenced (0.66) approaches, p > 0.05. CONCLUSIONS: Overall, the findings suggest there is no clear advantage of using the baseline-referenced approach over norm-referenced approach.

Acute post-traumatic stress symptoms and age predict outcome in military blast concussion.

High rates of adverse outcomes have been reported following blast-related concussive traumatic brain injury in US military personnel, but the extent to which such adverse outcomes can be predicted acutely after injury is unknown. We performed a prospective, observational study of US military personnel with blast-related concussive traumatic brain injury (n = 38) and controls (n = 34) enrolled between March and September 2012. Importantly all subjects returned to duty and did not require evacuation. Subjects were evaluated acutely 0-7 days after injury at two sites in Afghanistan and again 6-12 months later in the United States. Acute assessments revealed heightened post-concussive, post-traumatic stress, and depressive symptoms along with worse cognitive performance in subjects with traumatic brain injury. At 6-12 months follow-up, 63% of subjects with traumatic brain injury and 20% of controls had moderate overall disability. Subjects with traumatic brain injury showed more severe neurobehavioural, post-traumatic stress and depression symptoms along with more frequent cognitive performance deficits and more substantial headache impairment than control subjects. Logistic regression modelling using only acute measures identified that a diagnosis of traumatic brain injury, older age, and more severe post-traumatic stress symptoms provided a good prediction of later adverse global outcomes (area under the receiver-operating characteristic curve = 0.84). Thus, US military personnel with concussive blast-related traumatic brain injury in Afghanistan who returned to duty still fared quite poorly on many clinical outcome measures 6-12 months after injury. Poor global outcome seems to be largely driven by psychological health measures, age, and traumatic brain injury status. The effects of early interventions and longer term implications of these findings are unknown.

Brain-lung-thyroid disease: clinical features of a kindred with a novel thyroid transcription factor 1 mutation.

Brain-lung-thyroid disease is a rare familial disorder caused by mutations in thyroid transcription factor 1, a gene that regulates neuronal migration. We report the clinical features of ten patients from a single family with a novel gene mutation, including observations regarding treatment. Neurologic features of the kindred included developmental delay, learning difficulties, psychosis, chorea, and dystonia. Three patients had a history of seizure, which has not been previously reported in genetically confirmed cases. Low-dose dopamine-receptor blocking drugs were poorly tolerated in 2 patients who received this therapy, levodopa improved chorea in 3 of 4 children, and diazepam was markedly effective in a single adult patient. Chorea related to brain-lung-thyroid disease appears to respond paradoxically to antidopaminergic drugs. The unusual therapeutic response seen in our patients and others may help elucidate how disease-related migratory deficits affect neural pathways associated with motor control.

Effect of tetrabenazine on motor function in patients with huntington disease.

INTRODUCTION: Tetrabenazine (TBZ) reduces chorea related to Huntington disease (HD); however, it is uncertain whether this effect improves functionally relevant motor skills such as hand coordination and balance. The objective of this study was to provide pilot data regarding three motor function tests, which might be useful in monitoring symptom progression and therapeutic response, pending formal validation. METHODS: The authors assessed 11 ambulatory patients with HD-related chorea on two occasions: (1) while off TBZ (either prior to starting therapy or following a >24 h washout) and (2) when on a stable dose of TBZ, titrated to optimal effect. Study evaluations included the Jebsen-Taylor Hand Function Test (JTHFT) and Berg Balance Scale, a timed 25-foot walk, the Montreal Cognitive Assessment (MoCA) and the complete United Huntington Disease Rating Scale (UHDRS). RESULTS: Maximal chorea scores (UHDRS item 12) improved from 11.1 ± 2.9 to 8.5 ± 3.9 while on TBZ (P = 0.03), but we could not detect an improvement in functional measures while on TBZ in this small cohort. Scores of the JTHFT were globally slower than published normative data and correlated with MoCA summary scores, but not UHDRS chorea scores. CONCLUSIONS: This pilot study did not detect significant functional gains with chorea suppression. The fact that performance on tests of hand function correlates with MoCA but not UHDRS chorea scores highlights the need for additional treatments targeted toward the cognitive aspects of HD.

Transcutaneous electrical stimulation (TENS) for psychogenic movement disorders.

Psychogenic movement disorders (PMDs) often result in disability and diminished quality of life, yet medical therapies are presently limited and largely ineffective. On the basis of previous reports that transcutaneous electrical nerve stimulation (TENS) is helpful for certain patients with organic movement disorders, the authors studied the effects of TENS in 19 patients with PMDs, utilizing the Psychogenic Movement Disorder Rating Scale (PMDRS) as well as patient-rated assessments of PMD magnitude, persistence, and disability. The PMDRS Severity score significantly improved after a mean follow-up of 6.9 months, and short duration of PMD was found to be the only identifiable predictor of a favorable outcome. Although the tingling sensation produced by TENS makes it poorly suited for a controlled clinical trial, the device has a favorable side-effect profile and is an acceptable palliative treatment for a subset of PMD patients.

Correlation between Kinesia system assessments and clinical tremor scores in patients with essential tremor.

The primary aim of this study was to determine whether scores on The Essential Tremor Rating Assessment Scale (TETRAS) correlate with quantitative assessments using the Kinesia™ (CleveMed) system in patients with essential tremor (ET). Patients sequentially evaluated and diagnosed with ET at the Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine were enrolled in the study. The Kinesia portable device was attached to the wrist and subjects were instructed to hold their arms in an outstretched position and then touch their nose while data were wirelessly transmitted to a computer. Subjects were rated on the arm where the system was placed using specific TETRAS items. A linear regression model was constructed for each task using the logarithmic values of both clinical scores and objective motion data parameters to compute a Kinesia score. Twenty subjects underwent complete clinical TETRAS and Kinesia quantitative assessments. TETRAS clinical scores significantly correlated with predicted Kinesia quantitative variables for postural (r = 0.738; P < 0.001) and kinetic (r = 0.57; P = 0.009) tremor. We conclude that the Kinesia system may, therefore, have a utility in quantitative assessments of ET when combined with standard clinical assessment.

Symptomatic treatment of Huntington disease.

Huntington disease (HD) is a progressive heredoneurodegenerative disease manifested by chorea and other hyperkinetic (dystonia, myoclonus, tics) and hypokinetic (parkinsonism) movement disorders. In addition, a variety of psychiatric and behavioral symptoms, along with cognitive decline, contribute significantly to the patient's disability. Because there are no effective neuroprotective therapies that delay the progression of the disease, symptomatic treatment remains the cornerstone of medical management. Several classes of medications have been used to ameliorate the various symptoms of HD, including typical and atypical neuroleptics, dopamine depleters, antidepressants, antiglutamatergic drugs, GABA agonists, antiepileptic medications, acetylcholinesterase inhibitors, and botulinum toxin. Recently, surgical approaches including pallidotomy, deep brain stimulation, and fetal cell transplants have been used for the symptomatic treatment of HD. The selected therapy must be customized to the needs of each patient, minimizing the potential adverse effects. The primary aim of this article is to review the role of the different therapies, both available and investigational, for the treatment of the motor, psychiatric, behavioral, and cognitive symptoms of HD, and to examine their impact on the patient's functionality and quality of life.

Treatment of dystonia.

Dystonia varies in severity from simple focal dystonia, such as writer's cramp to life-threatening status dystonicus. Even though the pathophysiology is still elusive, symptomatic treatments may provide marked relief. Botulinum toxin is considered the treatment of choice for most focal and segmental dystonias. Deep brain stimulation of the basal ganglia, particularly the globus pallidus internum, is emerging as an important treatment for refractory, generalized, and segmental forms of dystonia. Gene therapy is also being explored as a possible treatment of inherited dystonias. This article reviews the therapeutic options available for the various types of dystonia.