Results of a Randomized Clinical Trial of Speech After Early Neurostimulation in Parkinson's Disease.

BACKGROUND: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone. OBJECTIVE: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments. METHODS: STN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN-DBS and BMT groups from baseline to 24 months. RESULTS: Over the 2-year period, changes in speech intelligibility and MPT, as well as patient-reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN-DBS and BMT groups, on medication and OFF STN-DBS, with patients in the STN-DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN-DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III. CONCLUSION: At this early stage of the patients' disease, STN-DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient-reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

How to improve patient education on deep brain stimulation in Parkinson's disease: the CARE Monitor study.

BACKGROUND: The introduction of deep brain stimulation (DBS) about 25 years ago provided one of the major breakthroughs in the treatment of Parkinson's disease (PD). However, a high percentage of patients are reluctant to undergo DBS. Previous research revealed that the critical step on the patient's path to DBS is the decision whether to undergo further diagnostic assessment for surgery at a specialized DBS-center. The aims of the current study were to evaluate how effective the combination of an outpatient DBS screening tool, STIMULUS, with specially developed educational material was to enhance patient education on DBS and to identify motivational aspects which influenced the patients' willingness to undergo further assessment. METHODS: In total, 264 patients were identified as appropriate candidates for DBS by general neurologists using the electronic preselection tool STIMULUS. Patient-centered information material was designed and handed out to support education on DBS. Further, several clinical characteristics and details of the patient counseling were documented. Refusal or consent to show up at a DBS center was registered over the following 16 months. RESULTS: 114 (43.2%) patients preselected as eligible for DBS (STIMULUS Score ≥ 6) agreed to show up at a specialized DBS center to undergo further diagnostic assessment. The patients' ages, PD classification as an akinetic-rigid type and the talks' topics side-effects of dopaminergic medication and the optimal time frame had a significant influence on the patients' decisions. CONCLUSIONS: The combination of preselection tools as STIMULUS with comprehensive information material is effective to increase DBS-acceptance rate in PD patients. Important topics of the information about DBS cover the optimal time frame for DBS surgery, the side-effects of dopaminergic medication as well as side-effects and complications of DBS surgery.

Functional impact of different muscle localization techniques for Botulinum neurotoxin A injections in clinical routine management of post-stroke spasticity.

BACKGROUND: Treatment options for spasticity include intramuscular botulinum neurotoxin A (BoNT-A) injections. Both ultrasound (US) or electromyographic (EMG) guided BoNT-A injections are employed to isolate muscles. To date, most studies have included patients naïve to BoNT-A or following a prolonged wash out phase. OBJECTIVE: To determine the impact of US/EMG guided BoNT-A injections on function in outpatients with spasticity receiving an established re-injection regime. METHODS: Thirty patients post-stroke were investigated in a single-blinded, randomized controlled trial using a cross-over design for the EMG and US and a parallel design for the control group. The Modified Ashworth (MAS), Disability Assessment (DAS), Quality of Life (EQ-5D), self-rating scale and Barthel Index were assessed pre- and post-BoNT-A injections of upper limb muscles by a to the injection technique blinded person. RESULTS: MAS improved in arm, finger and upper limb 4 weeks after BoNT-A treatment. The improvement showed no significant differences between the three injection techniques. Barthel Index, DAS and EQ-5D remained unchanged in all groups. CONCLUSIONS: This pilot study questions the impact of the instrumental guided injection techniques on everyday functionality in a routine clinical setting with established re-injection intervals. Larger trials are warranted with patients who are under long-term treatment on a regular basis.

Individual and culture-level components of survey response styles: A multi-level analysis using cultural models of selfhood.

Variations in acquiescence and extremity pose substantial threats to the validity of cross-cultural research that relies on survey methods. Individual and cultural correlates of response styles when using 2 contrasting types of response mode were investigated, drawing on data from 55 cultural groups across 33 nations. Using 7 dimensions of self-other relatedness that have often been confounded within the broader distinction between independence and interdependence, our analysis yields more specific understandings of both individual- and culture-level variations in response style. When using a Likert-scale response format, acquiescence is strongest among individuals seeing themselves as similar to others, and where cultural models of selfhood favour harmony, similarity with others and receptiveness to influence. However, when using Schwartz's (2007) portrait-comparison response procedure, acquiescence is strongest among individuals seeing themselves as self-reliant but also connected to others, and where cultural models of selfhood favour self-reliance and self-consistency. Extreme responding varies less between the two types of response modes, and is most prevalent among individuals seeing themselves as self-reliant, and in cultures favouring self-reliance. As both types of response mode elicit distinctive styles of response, it remains important to estimate and control for style effects to ensure valid comparisons.

Comparing the Fullerton Advanced Balance Scale with the Mini-BESTest and Berg Balance Scale to assess postural control in patients with Parkinson disease.

OBJECTIVES: To validate the Fullerton Advanced Balance (FAB) Scale for patients with idiopathic Parkinson disease (PD); and to compare the FAB Scale with the Mini-Balance Evaluation Systems Test (Mini-BESTest) and Berg Balance Scale (BBS). DESIGN: Observational study to assess concurrent validity, test-retest, and interrater reliability of the FAB Scale in patients with PD and to compare the distribution of the scale with the Mini-BESTest and BBS. SETTING: University hospital in an urban community. PARTICIPANTS: Patients with idiopathic PD (N=85; Hoehn and Yahr stages 1-4). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: FAB Scale, Mini-BESTest, BBS, timed Up and Go test, Unified Parkinson's Disease Rating Scale, and visual analog scale. RESULTS: Interrater (3 raters) and test-retest (3±1 d) reliability were high for all scales (ICCs≥.95). The FAB Scale was highly correlated with the Mini-BESTest (Spearman ρ=.87) and timed Up and Go test item of the Mini-BESTest (Spearman ρ=.83). In contrast with the BBS, the FAB Scale and Mini-BESTest have only minimal ceiling effects. The FAB Scale demonstrated the most symmetric distribution when compared with the Mini-BESTest and BBS (skewness: FAB scale: -.54; Mini-BESTest: -1.07; BBS: -2.14). CONCLUSIONS: The FAB Scale is a valid and reliable tool to assess postural control in patients with PD. No ceiling effect was noted for the FAB Scale. Although the items of the FAB Scale are more detailed when compared with the Mini-BESTest, interrater and test-retest reliability were excellent. The scale is a promising tool to detect small changes of the postural control system in individuals with PD.

Alexithymia-an independent risk factor for impulsive-compulsive disorders in Parkinson's disease.

Impulsive-compulsive disorders (ICDs) are frequent side effects of dopaminergic medication in Parkinson's disease (PD). Alexithymia, a personality trait characterized by difficulties identifying and describing feelings and an externally oriented thinking style, has been linked to various impulse-control problems in the general population. In PD, the prevalence of alexithymia is approximately twice as high as in the general population. However, whether alexithymia is associated with ICDs in PD is currently unknown. We examined the relationship between self-reported ICDs and alexithymia in a sample of 91 PD patients (89 on dopaminergic medication). Additional self-report measures assessed impulsivity, depression, anxiety, behavioral inhibition/approach, and emotion-regulation strategies. We observed that alexithymia, and particularly difficulty identifying feelings and difficulty describing feelings, was significantly correlated with ICDs, even when controlling for impulsivity, anxiety, and depression. In addition, a group analysis revealed that PD patients with clinical and moderate levels of alexithymia had significantly more ICDs than non-alexithymic patients, suggesting that even moderately high alexithymia levels increase the risk for ICDs in PD. Our results identify alexithymia as an independent risk factor for ICDs in PD. Thus, the inclusion of alexithymia in the neuropsychiatric assessment of patients with PD may help identify patients at risk for ICDs.

Characterizing mixed location hemorrhages/microbleeds with CSF markers.

OBJECTIVE: Cerebral amyloid angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions (intracerebral hemorrhage and/or cerebral microbleeds) and/or cortical superficial siderosis (cSS). In contrast, hemorrhagic lesions located in the deep structures are the hallmark of hypertensive arteriopathy (HTN-A). They are an exclusion criterion for CAA, and when present with lobar hemorrhagic lesions considered a separate entity: mixed location hemorrhages/microbleeds (MLHs). We compared clinical, radiological, and cerebrospinal fluid (CSF) marker data in patients with CAA, MLH, and Alzheimer's disease (AD), and healthy controls (HCs) and used it to position MLH in the disease spectrum. PATIENTS AND METHODS: Retrospective cohort study of consecutive patients with CAA (n = 31), MLH (n = 31), AD (n = 28), and HC (n = 30). Analysis of clinical, radiological, CSF biomarker (Aß42, Aß40, t-tau, and p-tau), and histopathological data in patients each group. RESULTS: cSS was significantly more common in CAA than MLH (45% vs 13%, p = 0.011), and cSS in MLH was associated with intracerebral hemorrhage (ICH) (p = 0.037). Aß42 levels and the Aß42/Aß40 ratio, diagnostic groups followed the order HC > MLH > CAA > AD and the opposite order for t-tau and p-tau. No clear order was apparent forAß40. Aß40 and Aß42 levels as well as the Aß42/Aß40 ratio were lower in both CAA and MLH patients with cSS than in patients without cSS. Aß40 and Aß42 levels were higher in CAA and MLH patients with lacunar infarcts than in those without. CONCLUSION: Our data suggest that MLH and CAA are mutually not exclusive diagnoses, and are part of a spectrum with variable contributions of both CAA and HTN-A.

Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy: New Data and Quantitative Meta-Analysis.

BACKGROUND: To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort. METHODS: Beta-amyloid 1-40 (Aß40), beta-amyloid 1-42 (Aß42), total tau (t-tau), and phosphorylated tau 181 (p-tau181) were measured in 31 patients with probable CAA, 28 patients with Alzheimer's disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aß42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted. RESULTS: In our data Aß42/40 (AUC 0.88) discriminated best between CAA and controls while Aß40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau181 (AUC 0.75) discriminated best in this study while Aß40 (AUC 0.58) and Aß42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aß42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aß40 (AUC 0.76), and p-tau181 (AUC 0.71). P-tau181 (AUC 0.76), Aß40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aß42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aß42/40 discriminated excellently between AD and controls (AUC 0.92-0.96) in this study as well as the meta-analysis. CONCLUSION: The analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ∼0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g., novel CSF biomarkers or other parameters might be more successful.

Clinical, ocular motor, and imaging profile of Niemann-Pick type C heterozygosity.

OBJECTIVE: To characterize subclinical abnormalities in asymptomatic heterozygote NPC1 mutation carriers as markers of neurodegeneration. METHODS: Motor function, cognition, mood, sleep, and smell function were assessed in 20 first-degree heterozygous relatives of patients with Niemann-Pick disease type C (NPC) (13 male, age 52.7 ± 9.9 years). Video-oculography and abdominal ultrasound with volumetry were performed to assess oculomotor function and size of liver and spleen. NPC biomarkers in blood were analyzed. 18F-fluorodesoxyglucose PET was performed (n = 16) to detect patterns of brain hypometabolism. RESULTS: NPC heterozygotes recapitulated characteristic features of symptomatic NPC disease and demonstrated the oculomotor abnormalities typical of NPC. Hepatosplenomegaly (71%) and increased cholestantriol (33%) and plasma chitotriosidase (17%) levels were present. The patients also showed signs seen in other neurodegenerative diseases, including hyposmia (20%) or pathologic screening for REM sleep behavior disorder (24%). Cognitive function was frequently impaired, especially affecting visuoconstructive function, verbal fluency, and executive function. PET imaging revealed significantly decreased glucose metabolic rates in 50% of participants, affecting cerebellar, anterior cingulate, parieto-occipital, and temporal regions, including 1 with bilateral abnormalities. CONCLUSION: NPC heterozygosity, which has a carrier frequency of 1:200 in the general population, is associated with abnormal brain metabolism and functional consequences. Clinically silent heterozygous gene variations in NPC1 may be a risk factor for late-onset neurodegeneration, similar to the concept of heterozygous GBA mutations underlying Parkinson disease.

Influence of subthalamic deep brain stimulation versus levodopa on motor perseverations in Parkinson's disease.

Patients with Parkinson's disease (PD) show impairment in generating random motor sequences reflecting a higher order motor deficit in set-shifting and suppression of perseverative behavior. The impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on motor perseverations has not yet been elucidated. In 35 patients with PD, we evaluated the effect of STN-DBS and levodopa on motor perseverations using the Vienna perseveration task. The task was performed 6 months after implantation of stimulation electrodes in the following three conditions: Stimulation off/medication off (Stim OFF/Med OFF), Stim ON/Med OFF, and Stim OFF/Med ON. Perseverations were measured by redundancy of second order (R(2)) with higher values indicating more severe perseverations. ANCOVA analysis revealed that influence of STN-DBS on R(2) significantly depended on R(2) severity during Stim OFF/Med OFF (F = 4.69, P = 0.035). Accordingly, we classified patients with PD into two groups based on the R(2) value during off treatment. In patients with mild perseveration (R(2) < 35) neither STN-DBS nor levodopa changed perseverations. By contrast, in patients with severe perseveration (R(2) > 35), STN-DBS significantly reduced R(2) by 9.7 +/- 2.6 (P < 0.001) whereas levodopa had no impact (R(2) reduction 3.7 +/- 1.6, P = 0.081). This demonstrates that STN-DBS, by reducing motor perseveration, influences higher order aspects of motor behavior of patients with PD.

Urinary symptoms, quality of life, and patient satisfaction in genetic and sporadic hereditary spastic paraplegia.

BACKGROUND: Urinary involvement is common in hereditary spastic paraplegias (HSPs), but has rarely been assessed systematically. METHODS: We characterized urinary complaints in 71 German HSP patients (mean age 55.4 ± 13.9 years; mean disease duration 20.7 ± 14.3 years; 48% SPG4-positive) using validated clinical rating scales (SCOPA-AUT, ICIQ-SF, ICIQ-LUTSqol). Treatment history and satisfaction with medical care was also assessed. RESULTS: 74.6% of patients had one or more urological problems, most commonly nocturia and urgency. Incontinence was more severe in women, correlating with SCOPA-AUT. Female gender and SPG4 mutations were associated with higher urinary frequency and severity of urological involvement. QoL was overall reduced, more in women and in SPG4 mutation carriers. Almost 90% consulted a medical specialist; more than half were largely satisfied. 43.4% received oral medication and 5.7% received intravesical botulinum toxin. However, more than one-third of patients remained untreated. CONCLUSION: Urinary complaints are common in HSP and should be addressed and treated.

Effect of water turbidity on the visual acuity of harbor seals (Phoca vitulina).

The underwater visual acuity (the angle subtended by the minimal resolvable line width of high contrast square wave gratings at a viewing distance of 2m) of two male harbor seals was determined at different levels of water turbidity. Starting with visual acuity angles of 5.5' and 12.7' in clear water we found visual acuity to decrease rapidly with increasing turbidity at rates of 7.4' and 6.0' per formazin nephelometric unit (FNU). Besides the individual differences in visual performance of the harbor seals tested, our results reveal a dramatic loss of visual acuity even at moderate levels of turbidity. At sites in the German Wadden Sea, where harbor seals are known to roam and forage, we measured turbidity levels exceeding 40FNU. These data suggest that turbidity has to be considered as an important factor in the sensory ecology of pinnipeds.

Comparison of the Fullerton Advanced Balance Scale, Mini-BESTest, and Berg Balance Scale to Predict Falls in Parkinson Disease.

BACKGROUND: The correct identification of patients with Parkinson disease (PD) at risk for falling is important to initiate appropriate treatment early. OBJECTIVE: This study compared the Fullerton Advanced Balance (FAB) scale with the Mini-Balance Evaluation Systems Test (Mini-BESTest) and Berg Balance Scale (BBS) to identify individuals with PD at risk for falls and to analyze which of the items of the scales best predict future falls. DESIGN: This was a prospective study to assess predictive criterion-related validity. SETTING: The study was conducted at a university hospital in an urban community. PATIENTS: Eighty-five patients with idiopathic PD (Hoehn and Yahr stages: 1-4) participated in the study. MEASUREMENTS: Measures were number of falls (assessed prospectively over 6 months), FAB scale, Mini-BESTest, BBS, and Unified Parkinson's Disease Rating Scale. RESULTS: The FAB scale, Mini-BESTest, and BBS showed similar accuracy to predict future falls, with values for area under the curve (AUC) of the receiver operating characteristic (ROC) curve of 0.68, 0.65, and 0.69, respectively. A model combining the items "tandem stance," "rise to toes," "one-leg stance," "compensatory stepping backward," "turning," and "placing alternate foot on stool" had an AUC of 0.84 of the ROC curve. LIMITATIONS: There was a dropout rate of 19/85 participants. CONCLUSIONS: The FAB scale, Mini-BESTest, and BBS provide moderate capacity to predict "fallers" (people with one or more falls) from "nonfallers." Only some items of the 3 scales contribute to the detection of future falls. Clinicians should particularly focus on the item "tandem stance" along with the items "one-leg stance," "rise to toes," "compensatory stepping backward," "turning 360°," and "placing foot on stool" when analyzing postural control deficits related to fall risk. Future research should analyze whether balance training including the aforementioned items is effective in reducing fall risk.

Validation of the questionnaire for impulsive-compulsive disorders in Parkinson's disease (QUIP) and the QUIP-rating scale in a German speaking sample.

Impulsive-compulsive disorders are frequent in patients with Parkinson's disease (PD). Recently, a screening questionnaire and rating scale were developed for these disorders: the questionnaire for impulsive-compulsive disorders (QUIP) and QUIP-rating scale (QUIP-RS). We assessed the validity of these instruments in the German language in order to reevaluate the benefit and to obtain German screening tools in clinical practice. A convenience sample of 156 patients was assessed in Kiel and Vienna. The patients filled out the QUIP-current, the QUIP-anytime and the QUIP-RS. We validated the questionnaires against a gold standard diagnosis via receiver operating characteristic curves and determined optimal cut-off scores for the instruments. Excluding walkabout, which was not shown to be valid, sensitivities ranged from 60-92 % for the QUIP-current, 68-91 % for the QUIP-anytime, and 73-100 % for the QUIP-RS. Specificities were >71 % for QUIP-current, >69 % for QUIP-anytime and >62 % for QUIP-RS. With its very good sensitivities, the QUIP-RS is a valid instrument to assess impulsive-compulsive disorders and makes an early detection of behavioral disorders in PD possible. The QUIP-anytime was also shown to be a valid screening instrument. Both are expected to prove useful in scientific and clinical practice.