Potential Prodromal Digital Postural Sway Markers for Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Detected via Dual-Tasking and Sensory Manipulation.

FXTAS is a neurodegenerative disorder occurring in some Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene premutation carriers (PMCs) and is characterized by cerebellar ataxia, tremor, and cognitive deficits that negatively impact balance and gait and increase fall risk. Dual-tasking (DT) cognitive-motor paradigms and challenging balance conditions may have the capacity to reveal markers of FXTAS onset. Our objectives were to determine the impact of dual-tasking and sensory and stance manipulation on balance in FXTAS and potentially detect subtle postural sway deficits in FMR1 PMCs who are asymptomatic for signs of FXTAS on clinical exam. Participants with FXTAS, PMCs without FXTAS, and controls underwent balance testing using an inertial sensor system. Stance, vision, surface stability, and cognitive demand were manipulated in 30 s trials. FXTAS participants had significantly greater total sway area, jerk, and RMS sway than controls under almost all balance conditions but were most impaired in those requiring vestibular control. PMCs without FXTAS had significantly greater RMS sway compared with controls in the feet apart, firm, single task conditions both with eyes open and closed (EC) and the feet together, firm, EC, DT condition. Postural sway deficits in the RMS postural sway variability domain in asymptomatic PMCs might represent prodromal signs of FXTAS. This information may be useful in providing sensitive biomarkers of FXTAS onset and as quantitative balance measures in future interventional trials and longitudinal natural history studies.

Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation: Cognitive Effects in GBA Mutation Carriers.

OBJECTIVE: This study was undertaken to compare the rate of change in cognition between glucocerebrosidase (GBA) mutation carriers and noncarriers with and without subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease. METHODS: Clinical and genetic data from 12 datasets were examined. Global cognition was assessed using the Mattis Dementia Rating Scale (MDRS). Subjects were examined for mutations in GBA and categorized as GBA carriers with or without DBS (GBA+DBS+, GBA+DBS-), and noncarriers with or without DBS (GBA-DBS+, GBA-DBS-). GBA mutation carriers were subcategorized according to mutation severity (risk variant, mild, severe). Linear mixed modeling was used to compare rate of change in MDRS scores over time among the groups according to GBA and DBS status and then according to GBA severity and DBS status. RESULTS: Data were available for 366 subjects (58 GBA+DBS+, 82 GBA+DBS-, 98 GBA-DBS+, and 128 GBA-DBS- subjects), who were longitudinally followed (range = 36-60 months after surgery). Using the MDRS, GBA+DBS+ subjects declined on average 2.02 points/yr more than GBA-DBS- subjects (95% confidence interval [CI] = -2.35 to -1.69), 1.71 points/yr more than GBA+DBS- subjects (95% CI = -2.14 to -1.28), and 1.49 points/yr more than GBA-DBS+ subjects (95% CI = -1.80 to -1.18). INTERPRETATION: Although not randomized, this composite analysis suggests that the combined effects of GBA mutations and STN-DBS negatively impact cognition. We advise that DBS candidates be screened for GBA mutations as part of the presurgical decision-making process. We advise that GBA mutation carriers be counseled regarding potential risks associated with STN-DBS so that alternative options may be considered. ANN NEUROL 2022;91:424-435.

Inattentional blindness to DWI lesions in spontaneous intracerebral hemorrhage.

PURPOSE: Inattentional blindness refers to when an individual fails to recognize an event or object due to their awareness being engaged in a different task and has been described in radiology. The purpose of this study is to determine whether the sensitivity of detecting diffusion-weighted imaging (DWI) lesions in spontaneous intracerebral hemorrhage (sICH) is reduced due to inattentional blindness. METHODS: Using a prospective observational cohort, select sICH patients received an MRI scan within 72 h of admission. The scans were subject to an "official read" that occurred as part of the routine workflow. Separately, each scan underwent two "preliminary research reads" with task-specific instructions to detect DWI lesions. A "final research read" via three-party adjudication was used to calculate sensitivity and specificity for detecting these lesions. Board-certified neuroradiologists blinded to the clinical history of the patients reviewed all imaging. RESULTS: Amongst 121 sICH participants with research MRI scans, 49.6% (n = 60) scans were noted to have DWI lesion on their "final research read." The "official read" detected these DWI lesions with a sensitivity of 65% (95% CI, 52-77%). In contrast, the "preliminary research read" sensitivity for readers 1 and 2 was 98% (CI 95%, 91 to 100%) and 87% (CI 95%, 75 to 94%), respectively. Both were significantly different (p < 0.05) from the sensitivity of the "official read." CONCLUSIONS: Given the increased sensitivity with task-specific instructions, our results suggest that inattentional blindness may be leading to the decreased detection of DWI lesions in patients with concomitant sICH.

The impact and feasibility of a brief, virtual, educational intervention for home healthcare professionals on Parkinson's Disease and Related Disorders: pilot study of I SEE PD Home.

BACKGROUND: Individuals with advanced Parkinson's Disease (PD) and Parkinson-related disorders (PRD) are frequently referred for home allied therapies and nursing care, yet home healthcare professionals have limited training in PD/PRD. While recognizing the need for such care, patients and families report home healthcare professionals are unfamiliar with these conditions, which may be driven by neurophobia and may contribute to suboptimal care and early termination of services. We sought to determine the feasibility and effects of a virtual, multimodal educational intervention on PD knowledge, confidence, and empathy among home health professionals. METHODS: Home health nurses, occupational therapists, physical therapists and physical therapy assistants, and speech-language pathologists participated in a daylong, virtual symposium on advanced PD/PRD, combining focused lectures, discipline-specific breakout sessions, immersive virtual reality vignettes, and interactive panels with both patients and families, and movement disorders and home healthcare experts. Participants completed online pre- and post-symposium surveys including: demographics; PD/PRD knowledge (0-10 points possible); empathy (Interpersonal Reactivity Index); and 10-point scales of confidence with and attitudes towards individuals with PD/PRD, respectively. Pre-post intervention changes and effect sizes were evaluated with paired t-tests and Cohen's d. We performed qualitative analyses of post-symposium free-text feedback using a grounded theory approach to identify participants' intentions to change their practice. RESULTS: Participants had a mean improvement of 3.1 points on the PD/PRD knowledge test (p < 0.001, d = 1.97), and improvement in confidence managing individuals with PD/PRD (p = 0.0003, d = .36), and no change in empathy. The interactive, virtual format was rated as effective by 95%. Common themes regarding symposium-motivated practice change included: interdisciplinary collaboration; greater involvement and weighting of the patient and caregiver voice in care plans; attention to visit scheduling in relation to patient function; recognition and practical management of the causes of sudden change in PD/PRD, including infections and orthostatic hypotension. CONCLUSIONS: A virtual, multimodal, brief educational pilot intervention improved PD/PRD-specific knowledge and confidence among home healthcare nurses and allied health professionals. Future studies are necessary to test the short- and long-term effects of this intervention more broadly and to investigate the impact of this education on patient and caregiver outcomes.

The Effects of Dual Task Cognitive Interference and Fast-Paced Walking on Gait, Turns, and Falls in Men and Women with FXTAS.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a genetic neurodegenerative disorder characterized by cerebellar ataxia, tremor, and cognitive dysfunction. We examined the impact of dual-task (DT) cognitive-motor interference and fast-paced (FP) gait on gait and turning in FXTAS. Thirty participants with FXTAS and 35 age-matched controls underwent gait analysis using an inertial sensor-based 2-min walk test under three conditions: (1) self-selected pace (ST), (2) FP, and (3) DT with a concurrent verbal fluency task. Linear regression analyses were performed to assess the association between FXTAS diagnosis and gait and turn outcomes. Correlations between gait variables and fall frequency were also calculated. FXTAS participants had reduced stride length and velocity, swing time, and peak turn velocity and greater double limb support time and number of steps to turn compared to controls under all three conditions. There was greater dual task cost of the verbal fluency task on peak turn velocity in men with FXTAS compared to controls. Additionally, stride length variability was increased and cadence was reduced in FXTAS participants in the FP condition. Stride velocity variability under FP gait was significantly associated with the number of self-reported falls in the last year. Greater motor control requirements for turning likely made men with FXTAS more susceptible to the negative effects of DT cognitive interference. FP gait exacerbated gait deficits in the domains of rhythm and variability, and increased gait variability with FP was associated with increased falls. These data may inform the design of rehabilitation strategies in FXTAS.

Association of Longitudinal Glycemia with Diffusion Weighted Imaging Lesions in Spontaneous Intracerebral Hemorrhage.

OBJECTIVES: Higher glycemia on admission has been associated with diffusion weighted imaging (DWI) lesions in patients with spontaneous intracerebral hemorrhage (sICH). However, the influence of longitudinal glycemia after admission and during a patient's hospitalization on DWI lesions in sICH has not been studied. Our aim was to compare longitudinal glycemia in sICH patients with and without DWI lesions. MATERIAL AND METHODS: Glycemia measurements were abstracted on participants enrolled in a prospective observational study examining predictors for DWI lesions in sICH. Univariate analysis was used to compare mean longitudinal glycemia in sICH patients with and without DWI lesions. Logistical regression was used to determine whether mean longitudinal glycemia was predictive of DWI lesions. RESULTS: DWI lesions were found in 60 of the 121 (49.6%) participants. Mean time-to-MRI was 99.6 h (SD ± 89). During this time interval, 2,101 glucose measurements were analyzed with a median number of 7 (IQR 12, 1-261) measurements per patient. Mean longitudinal glycemia was higher in the DWI positive group compared to the DWI negative group until time-to-MRI (132 mg/dL vs 122 mg/dL, p = 0.03). Mean longitudinal glycemia was found to be predictive of DWI lesions (OR 1.02, 95% CI 1.005 to 1.035, p = 0.011). CONCLUSIONS: Mean longitudinal glycemia was higher in sICH patients with DWI lesions compared to those without DWI lesions. Future research into the association between higher glycemia and DWI lesions in sICH may provide insight into a pathophysiologic mechanism.

Brain Atrophy and Leukoaraiosis Correlate with Futile Stroke Thrombectomy.

INTRODUCTION: Although mechanical thrombectomy (MT) is a proven therapy for acute large vessel occlusion strokes, futile recanalization in the elderly is common and costly. Strategies to minimize futile recanalization may reduce unnecessary thrombectomy transfers and procedures. We evaluated whether a simple and rapid visual assessment of brain atrophy and leukoaraiosis on a plain head CT correlates with futile stroke recanalization in the elderly. METHODS: Consecutive stroke patients admitted for thrombectomy, older than 65 years of age, all with TICI 2b/3 recanalization rates were retrospectively studied from multiple comprehensive stroke centers. Brain atrophy and leukoaraiosis were visually analyzed from pre-intervention plain head CTs using a simplified scheme based on validated scales. Baseline demographics were collected and the primary outcome measure was 90-day modified Rankin score (mRS). Cochran-Armitage trend test was applied in analyzing the association of the severity of brain atrophy and leukoaraiosis with 90-day mRS. RESULTS: Between 2017 and 2019, 175 patients > 65 years who underwent thrombectomy with TICI 2b/3 recanalization from two comprehensive stroke centers were evaluated. The median age was 77 years. IV-tPA was given in 59% of patients, average initial NIHSS was 19, average baseline mRS was 0.77 and median time to recanalization was 300 minutes. Age and severity of atrophy/leukoaraiosis was categorized into three groups of increasing severity and associated with 90 day mRS 0-3 rates of 62%, 49% and 41% (p=0.037) respectively. CONCLUSIONS: A simplified, visual assessment of the degree of brain atrophy and leukoaraiosis measured on plain head CT correlates with futile recanalization in patients age >65 years. Although additional validation is needed, these findings suggest that brain atrophy and leukoaraiosis may have value as a surrogate marker of prestroke functional status. In doing so, simplified visual plain head CT grading scales may minimize elderly futile recanalization.

A Novel DBS Paradigm for Axial Features in Parkinson's Disease: A Randomized Crossover Study.

BACKGROUND: High-frequency (130-185 Hz) deep brain stimulation (DBS) of the subthalamic nucleus is more effective for appendicular than axial symptoms in Parkinson's disease (PD). Low-frequency (60-80 Hz) stimulation (LFS) may reduce gait/balance impairment but typically results in worsening appendicular symptoms. We created a "dual-frequency" programming paradigm (interleave-interlink, IL-IL) to address both axial and appendicular symptoms. In IL-IL, 2 overlapping LFS programs are applied to the DBS lead, with the overlapping area focused on the optimal cathode. The nonoverlapping area (LFS) is thought to reduce gait/balance impairment, whereas the overlapping area (high-frequency stimulation, HFS) aims to control appendicular symptoms. METHODS: We performed a randomized, double-blind crossover trial comparing patients' previously optimized IL-IL and conventional HFS paradigms. Each arm was 2 weeks in duration. The primary outcome measure was the patient/caregiver Modified Clinical Global Impression Severity (CGI-S). Secondary outcome measures included blinded motor evaluations, timed tests, patient/caregiver questionnaires, and Personal KinetiGraphs (PKG). RESULTS: Twenty-five patients were enrolled, and 20 completed. The patient/caregiver CGI-S for gait/balance (P = 0.01) and appendicular symptom control (P = 0.001), and the blinded rater MDS-UPDRS-III (-5.22, P = 0.02), CGI-S gait/balance (P = 0.01), and CGI-S speech (P = 0.02) were better while on IL-IL. Scores on Parkinson's Disease Quality of Life (P = 0.002) and Freezing-of-Gait Questionnaires (P = 0.04) were better on IL-IL. The Timed-Up-and-Go was 9.8% faster (P = 0.01), with 11.8% reduction in steps (P = 0.001) on IL-IL. There was no difference in PKG bradykinesia (P = 0.18) or tremor (P = 0.23) between paradigms. CONCLUSIONS: Our results prompt consideration of this novel programming paradigm (IL-IL) for PD patients with axial symptom impairment as a new treatment option for both axial and appendicular symptoms. © 2020 International Parkinson and Movement Disorder Society.

Fragile X Gray Zone Alleles Are Associated With Signs of Parkinsonism and Earlier Death.

BACKGROUND: Premutation size (55-199 CGG repeats) in the fragile X mental retardation 1 (FMR1) gene cause fragile X-associated tremor/ataxia syndrome, but it is unclear whether smaller "gray" zone expansions of 41-54 repeats are also associated with movement disorders. The objectives of this study were to determine the association between the FMR1 gene gray zone expansions, AGG interspersions, and the presence of parkinsonism and motor and cognitive function in an elderly community-based population. METHODS: Automated FMR1 polymerase chain reaction was performed on existing samples from 2 longitudinal aging studies whose subjects agreed to brain donation. A detailed clinical evaluation including a modified Unified Parkinson's Disease Rating Scale score, a composite score of global motor function, 17 cognitive tests summarized as a global measure of cognition, and neuropathological examination were obtained for genotyped participants. RESULTS: The average age of the population (n = 2362) was 85.9 ± 7.3 years, and average age at death was 88.6 ± 6.4 years (n = 1326), with 72% women. The prevalence of FMR1 gray zone alleles was 5.2% (122 of 2362). There was no difference between participants with gray zone expansions or those lacking AGG interspersions compared with normal participants in global cognition, global motor function, clinical diagnosis, or pathological changes. Gray zone alleles were associated with signs of parkinsonism in men (P = 0.01), and gray zone carrier men were more likely to die (hazard ratio, 2.34; 95% confidence interval, 1.31-4.16). CONCLUSIONS: This is the largest study to investigate gray zone alleles in a community population. The key findings are that in men, the gray zone allele is associated with signs of parkinsonism and higher risk of death, but not with intranuclear neuronal inclusions. © 2020 International Parkinson and Movement Disorder Society.

The Influence of Diffusion Weighted Imaging Lesions on Outcomes in Patients with Acute Spontaneous Intracerebral Hemorrhage.

BACKGROUND/OBJECTIVE: Diffusion weighted imaging (DWI) lesions have been well described in patients with acute spontaneous intracerebral hemorrhage (sICH). However, there are limited data on the influence of these lesions on sICH functional outcomes. We conducted a prospective observational cohort study with blinded imaging and outcomes assessment to determine the influence of DWI lesions on long-term outcomes in patients with acute sICH. We hypothesized that DWI lesions are associated with worse modified Rankin Scale (mRS) at 3 months after hospital discharge. METHODS: Consecutive sICH patients meeting study criteria were consented for an magnetic resonance imaging (MRI) scan of the brain and evaluated for remote DWI lesions by neuroradiologists blinded to the patients' hospital course. Blinded mRS outcomes were obtained at 3 months. Logistic regression was used to determine significant factors (p < 0.05) associated with worse functional outcomes defined as an mRS of 4-6. The generalized estimating equation (GEE) approach was used to investigate the effect of DWI lesions on dichotomized mRS (0-3 vs 4-6) longitudinally. RESULTS: DWI lesions were found in 60 of 121 patients (49.6%). The presence of a DWI lesion was associated with increased odds for an mRS of 4-6 at 3 months (OR 5.987, 95% CI 1.409-25.435, p = 0.015) in logistic regression. Using the GEE model, patients with a DWI lesion were less likely to recover over time between 14 days/discharge and 3 months (p = 0.005). CONCLUSIONS: DWI lesions are common in primary sICH, occurring in almost half of our cohort. Our data suggest that DWI lesions are associated with worse mRS at 3 months in good grade sICH and are predictive of impaired recovery after hospital discharge. Further research into the pathophysiologic mechanisms underlying DWI lesions may lead to novel treatment options that may improve outcomes associated with this devastating disease.

Do certain subpopulations of adults with drug-resistant epilepsy respond better to modified ketogenic diet treatments? Evaluation based on prior resective surgery, type of epilepsy, imaging abnormalities, and vagal nerve stimulation.

OBJECTIVE: Adults with drug-resistant epilepsy (DRE) are among the most challenging to treat. This study assessed whether specific subpopulations of adult patients with refractory epilepsy responded differently to modified ketogenic diet (MKD) therapy. METHODS: Changes in seizure frequency, severity, and quality of life (QOL) were retrospectively analyzed based on pre-MKD surgical history, type of epilepsy, imaging findings, and vagal nerve stimulation (VNS) history among adults, ≥17 years of age, with DRE, receiving MKD therapy for three months. Additionally, particular attention was made to medication and VNS adjustments. RESULTS: Responder rates in seizure frequency, severity, and QOL reported among those with prior surgery were 56%, 75%, and 94%, respectively. Among those with focal epilepsy: 57%, 76%, and 76% had improvements in seizure frequency, seizure severity, and QOL, respectively whereas 83% improvement was seen for all three measures in those with generalized epilepsy. Among those with abnormal imaging: just over 50% reported improvements on all measures. For those with VNS, 53%, 63%, and 95% had improvements in seizure frequency, seizure severity, and QOL, respectively. No statistical differences in seizure frequency, severity, or QOL were noted between groups based on prediet surgical history, seizure type, imaging abnormalities, or VNS history. Compared with expected improvement from medication adjustment alone, significant improvement was seen for all groups; notably, the Z-test for proportions for the surgery group, when compared with placebo responder rates at 20%, was 3.6, p < 0.001. CONCLUSIONS: Modified ketogenic diet therapies are effective in improving seizure frequency, severity, and QOL and may offer the best chance for improvement among those whose seizures have persisted despite surgical intervention and VNS therapy. All types of epilepsy respond to MKDs, and possibly those with generalized epilepsy may respond better.

Modified ketogenic diets in adults with refractory epilepsy: Efficacious improvements in seizure frequency, seizure severity, and quality of life.

OBJECTIVE: This study evaluates the efficacy of a modified ketogenic diet (MKD) on seizure frequency, severity, and quality of life (QOL), as well as potential complications of MKD therapy among adults with drug-resistant epilepsy (DRE). METHODS: Changes in seizure frequency, severity, QOL, and side effects were retrospectively examined among adults, ≥17 years of age, with DRE (≥2 antiepileptic drugs [AEDs]), after 3 months of MKD therapy. Attention was paid to medication or vagus nerve stimulator (VNS) changes as well to evaluate potential confounders. RESULTS: A total of 60% (n = 33) of the 55 individuals reported ≥50% seizure frequency improvement, 42 (76%) reported improvement in seizure severity, and 48 (87%) reported improvement in QOL. More patients following a modified ketogenic diet - 15 g net carbohydrate daily (MKD-15) (95%) compared with a MKD-50 (69%) reported improvement in QOL (p = 0.02). Weight among the entire sample declined from 77.5 (20) kg to 73.9 (19.0) kg (p < 0.0001), and total cholesterol (TC), low density lipoprotein (LDL), and total cholesterol:high density lipoprotein (TC:HDL) increased significantly (p = 0.03, p = 0.04, and p = 0.02, respectively). Free carnitine values were available for a select number of patients, 26 (47%) at baseline, and 7 (13%) at follow-up, of which 8 (31%) at baseline, and 2 (29%) at follow-up had carnitine deficiency (<25 nmol/mL). Constipation was noted in 5 patients (9%), and no kidney stones were reported during the study period. There were no statistical differences in number or dose changes for AED or VNS during the study period. SIGNIFICANCE: Modified ketogenic diet therapies reduce seizure frequency and severity and improve QOL among adults with DRE with few side effects outside of weight loss, a desired outcome among many adults with DRE. More restrictive MKDs may offer improved seizure severity and QOL. Modified ketogenic diet therapy increases LDL cholesterol, which may be cardioprotective if related to an increase in LDL particle size with high saturated fat intake; however, more research is needed examining LDL particle size changes among those receiving MKD therapy.

The Influence of Weather on the Incidence of Primary Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage has been associated with changes in various weather conditions. The primary aim of this study was to examine the collective influence of temperature, barometric pressure, and dew point temperature on the incidence of primary spontaneous intracerebral hemorrhage (sICH). METHODS: Between January 2013 and December 2016, patients with sICH due to hypertension or amyloid angiopathy with a known time of onset were identified prospectively. Meteorological variables 6 hours prior to time of onset were obtained from the National Oceanic Atmospheric Administration via two weather stations. Using a Monte-Carlo simulation, random populations of meteorological conditions in a 6-hour time window during the same years were generated. The actual meteorological conditions 6-hours prior to sICH were compared to those from the randomly generated populations. The false discovery rate method was used to identify significant meteorological variables. RESULTS: Time of onset was identified in 455 of 603 (75.5%) patients. Distribution curves for change in temperature, mean barometric pressure, and change in barometric pressure 6-hours prior to hemorrhage ictus were found to be significantly different from the random populations. (FDR approach P < .05). For a given change in temperature associated with intracerebral hemorrhage, mean barometric pressure was higher (1018 millibar (mb) versus 1016 mb, P = .03). Barometric pressure data was not influenced by variations in temperature. CONCLUSIONS: We concluded that barometric pressure primarily influences the incidence of intracerebral hemorrhage. The association described in the literature between temperature and intracerebral hemorrhage is likely confounded by variations in barometric pressure.

Accuracy of Microelectrode Trajectory Adjustments during DBS Assessed by Intraoperative CT.

BACKGROUND/AIMS: Microelectrode recording (MER)-guided deep brain stimulation (DBS) aims to place the DBS lead in the optimal electrophysiological target. When single-track MER or test stimulation yields suboptimal results, trajectory adjustments are made. The accuracy of these trajectory adjustments is unknown. Intraoperative computed tomography can visualize the microelectrode (ME) and verify ME adjustments. We aimed to determine the accuracy of ME movements in patients undergoing MER-guided DBS. METHODS: Coordinates following three methods of adjustment were compared: (1) those within the default "+" configuration of the ME holder; (2) those involving rotation of the default "+" to the "x" configuration; and (3) those involving head stage adjustments. Radial error and absolute differences between coordinates were determined. RESULTS: 87 ME movements in 59 patients were analyzed. Median (IQR) radial error was 0.59 (0.64) mm. Median (IQR) absolute x and y coordinate errors were 0.29 (0.52) and 0.38 (0.44) mm, respectively. Errors were largest after rotating the multielectrode holder to its "x"-shaped setup. CONCLUSION: ME trajectory adjustments can be made accurately. In a considerable number of cases, errors exceeding 1 mm were found. Adjustments from the "+" setup to the "x" setup are most prone to inaccuracies.

Borders of STN determined by MRI versus the electrophysiological STN. A comparison using intraoperative CT.

BACKGROUND: It is unclear which magnetic resonance imaging (MRI) sequence most accurately corresponds with the electrophysiological subthalamic nucleus (STN) obtained during microelectrode recording (MER, MER-STN). CT/MRI fusion allows for comparison between MER-STN and the STN visualized on preoperative MRI (MRI-STN). OBJECTIVE: To compare dorsal and ventral STN borders as seen on 3-Tesla T2-weighted (T2) and susceptibility weighted images (SWI) with electrophysiological STN borders in deep brain stimulation (DBS) for Parkinson's disease (PD). METHODS: Intraoperative CT (iCT) was performed after each MER track. iCT images were merged with preoperative images using planning software. Dorsal and ventral borders of each track were determined and compared to MRI-STN borders. Differences between borders were calculated. RESULTS: A total of 125 tracks were evaluated in 45 patients. MER-STN started and ended more dorsally than respective dorsal and ventral MRI-STN borders. For dorsal borders, differences were 1.9 ± 1.4 mm (T2) and 2.5 ± 1.8 mm (SWI). For ventral borders, differences were 1.9 ± 1.6 mm (T2) and 2.1 ± 1.8 mm (SWI). CONCLUSIONS: Discrepancies were found comparing borders on T2 and SWI to the electrophysiological STN. The largest border differences were found using SWI. Border differences were considerably larger than errors associated with iCT and fusion techniques. A cautious approach should be taken when relying solely on MR imaging for delineation of both clinically relevant STN borders.

Comparison of neuropathology in Parkinson's disease subjects with and without deep brain stimulation.

BACKGROUND: The aim of this postmortem study was to compare, in Parkinson's disease subjects with and without bilateral subthalamic nucleus deep brain stimulation (STN-DBS), the loss of pigmented neurons within the substantia nigra and pathological alpha-synuclein density within the SN and other brain regions. METHODS: PD subjects were identified from the Arizona Study of Aging and Neurodegenerative Disorders database (STN-DBS = 11, non-DBS = 156). Pigmented neuron loss scores within the substantia nigra as well as alpha-synuclein density scores within the substantia nigra and 9 other brain regions were compared, the latter individually and in summary as the Lewy body brain load score. RESULTS: DBS subjects had higher alpha-synuclein density scores within the substantia nigra, olfactory bulb, and locus ceruleus, as well as higher total Lewy body brain load scores when compared with non-DBS subjects. No differences in substantia nigra pigmented neuron loss scores were found. CONCLUSIONS: STN-DBS subjects tend to have higher alpha-synuclein density scores, but do not have a differential loss of substantia nigra pigmented neurons. © 2016 International Parkinson and Movement Disorder Society.

Depression and Anxiety Following Aneurysmal Subarachnoid Hemorrhage Are Associated With Higher Six-Month Unemployment Rates.

Although survival has dramatically improved following aneurysmal subarachnoid hemorrhage (aSAH), the reasons for persistent high rates of unemployment in this population remain unknown. Retrospective review for medical records of patients with aSAH admitted to Rush University Medical Center was undertaken. Multivariate logistic regression models were used to test the association of either depression or anxiety with the 6-month employment status. Among the 29 patients who developed depression or anxiety, 86.2% were unemployed at 6 months following their aSAH. After controlling for confounding factors, anxiety and depression were significantly associated with higher 6-month unemployment rates (odds ratio [OR]=0.08, 95% confidence interval [CI]=0.02-0.3, p=0.0002). Depression and anxiety are common following aSAH and are associated with increased unemployment rates 6 months post aSAH.

The impact of antidepressants on seizure frequency and depressive and anxiety disorders of patients with epilepsy: Is it worth investigating?

PURPOSE: Depression and anxiety disorders in patients with epilepsy (PWE) remain under-recognized and under-treated, despite being the most common psychiatric co-morbidities. Selective serotonin re-uptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are considered first-line treatment for primary depression and anxiety disorders. We performed this study to investigate if SSRIs and SNRIs could affect the seizure frequency of PWE and to assess whether such effect is independent of the response of the mood and anxiety disorders to these drugs. METHODS: This was a retrospective study of 100 consecutive PWE who were started on an SSRI or SNRI for the treatment of a depressive and/or anxiety disorder. Every patient underwent a psychiatric evaluation by one of the investigators using a semi-structured interview who also managed the pharmacologic treatment in all the patients. Patients were excluded if they had a diagnosis of psychogenic non-epileptic seizures or if they had undergone epilepsy surgery or the implant of the vagal nerve stimulator six months before and after the start of the antidepressant therapy. The final analysis was conducted in 84 patients. For each type of seizure, an average and maximal monthly seizure frequency during the six months preceding and following the start of psychotropic drugs was extracted from the medical records. We identified the number of patients whose seizure frequency during treatment with antidepressants: (i) shifted from a <1/month to a ≥1 seizure/month and vice-versa, (ii) increased beyond maximal/monthly baseline frequency, and (iii) patients who developed de-novo generalized tonic-clonic (GTC) seizures. RESULTS: None of the patients with a baseline seizure frequency <1seizure/month went on to have ≥1seizure/month after initiating treatment with antidepressants, had an increase in frequency beyond baseline maximal counts or developed de-novo-GTC seizures. Furthermore, there was no seizure recurrence among patients that had been seizure-free. Among the patients with a baseline seizure frequency ≥1/month, 27.5% had a reduction in seizure frequency to <1/month, which suggested a positive effect of SSRI/SNRI on seizure frequency (p=0.001, McNemar test). Among the patients with a baseline seizure frequency ≥1seizure/month, 48% exhibited a >50% reduction in seizure frequency after the start of treatment with SSRIs or SNRIs. A therapeutic response to SSRIs and SNRIs was found in 73% of patients. The change in seizure frequency was independent of the improvement in psychiatric symptomatology. CONCLUSION: In this retrospective observational study, SSRIs or SNRIs did not appear to worsen seizure frequency. Also, in patients with frequent seizures, SSRIs and SNRIs may be associated with a possible decrease in seizure frequency. Furthermore, these drugs appear to yield good therapeutic response of psychiatric symptoms independently of seizure frequency. It is pivotal to replicate these data in prospective, double-blind, placebo-controlled trials.

Three-Month Outcomes Are Poor in Stroke Patients with Cancer Despite Acute Stroke Treatment.

INTRODUCTION: Stroke risk is increased in cancer patients. Prognosis in these patients is poor, with higher in-hospital mortality and increased subsequent mortality. However, data on stroke in cancer patients are limited, specifically regarding acute stroke treatment and functional outcomes. We aim to determine the functional outcomes of cancer patients admitted with acute stroke. MATERIALS AND METHODS: We retrospectively reviewed patients carrying a diagnosis of cancer who were admitted with acute ischemic stroke between March 2013 and February 2016. Demographics, cerebrovascular risk factors, stroke characteristics including acute treatment, and characteristics of their cancer history and treatment were abstracted. The primary outcome measures included in-hospital mortality and 3-month functional outcome (as assessed by the modified Rankin Scale [mRS] score, with mRS scores of 3-6 considered poor functional outcome). Further outcome measures included length of stay and discharge destination. FINDINGS: Forty-nine patients met the inclusion criteria, with a median admission National Institutes of Health Stroke Scale score of 8. Twelve patients (24.4%) underwent acute stroke treatment. The most common stroke etiology was hypercoagulability of malignancy (21, 42.9%). The three-month mortality was 46.9%; half of survivors had poor functional outcome. Functional outcomes did not differ by cancer type, stage, or year since diagnosis; on multivariate analysis only high admission NIHSS score was associated with poor functional outcome (P = .002). CONCLUSION: Nearly half of patients with cancer and stroke die within 3 months, and functional outcome is poor for 50% of 3-month survivors despite consideration of acute stroke treatment. Future research should address the role of hypercoagulability in the outcome prediction of stroke patients with cancer.