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.

A clinical test for the alcohol sensitivity of essential tremor.

BACKGROUND: The objective of the study was to develop a simple diagnostic test for alcohol sensitivity of essential tremor patients. Here we describe the controlled measurements of tremor severity after alcohol ingestion and the practicability of using it as a home test. METHODS: Ten patients were tested for alcohol sensitivity under controlled conditions in the laboratory (blood alcohol, quantitative tremor recordings, modified Fahn scale, visual analog scale, Archimedes spirals), and 15 patients were instructed to perform an alcohol test at home (visual analog scale, Archimedes spirals) following an adapted dosage of alcohol. RESULTS: The time course of the antitremor effect showed significant improvement of up to 50% in both groups for all the outcome parameters. Tremor deteriorated after 3 hours. A quarter of the patients noticed the alcohol effect for the first time during the test. CONCLUSIONS: Alcohol is an effective drug for essential tremor. Its effect is only short-lived and exhibits a rebound after > 3 hours and the next morning. We propose this essential tremor home test as a diagnostic tool to confirm the alcohol sensitivity of essential tremor.

Quality of life predicts outcome of deep brain stimulation in early Parkinson disease.

OBJECTIVE: To investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications. METHODS: We performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson's Disease Rating Scale (UPDRS) (UPDRS-III "off" and "on" medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI. RESULTS: PDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups (p < 0.05). The higher the baseline score (worse QOL) the larger the improvement in QOL after 24 months. No correlation was found for any of the other baseline characteristics analyzed in either treatment group. CONCLUSION: Impaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS. CLINICALTRIALSGOV IDENTIFIER: NCT00354133.

Idiopathic delayed-onset edema surrounding deep brain stimulation leads: Insights from a case series and systematic literature review.

INTRODUCTION: Deep brain stimulation (DBS) is effective for some neurological and psychiatric conditions. Idiopathic delayed-onset edema (IDE) surrounding the leads has been anecdotally reported. The etiology, predisposing factors and prognosis of this complication are unknown. We present a multicenter case series of patients with IDE, and a systematic literature review, aimed at defining the pathophysiology and identifying appropriate treatment strategies. METHODS: IDE was defined as edema along the DBS lead, occurring ≥72 h postoperatively, in absence of trauma, vascular events or infection. Information on patients with IDE was collected in a standardized way. A systematic search was performed in Pubmed. RESULTS: Twelve new patients presenting with 14 episodes of IDE are described. From the literature, 38 patients were identified. No common surgical aspects or patient-related factors were identified as risk predictors for the onset of IDE. Symptoms included deterioration of the stimulation effect, seizures and focal neurological signs. Although the condition is self-limiting, with symptoms resolution in 28.5 days on average, three patients underwent surgical revision and seven received antibiotics. CONCLUSIONS: IDE is a rare complication of DBS procedures, presenting from few days to months after surgery. Symptoms can be mild and not-specific, and the condition is self-limiting. The diagnosis of IDE is made after exclusion of vascular events or infections. The pathophysiology is still unexplained. The recognition of this complication can help avoiding unnecessary surgical procedures (system explantation) and antibiotic treatment.

Vascular occlusion sites determine differences in lesion growth from early apparent diffusion coefficient lesion to final infarct.

BACKGROUND AND PURPOSE: Occlusion of major cerebral arteries is the primary source of tissue damage in ischemic stroke and the target of thrombolytic therapy. We hypothesized that large infarcts in more proximal vascular occlusions correspond with substantially increased ischemic lesions shown on initial apparent diffusion coefficient (ADC) maps. METHODS: Initial ADC lesions in 120 patients with acute ischemic stroke were analyzed within 6 hours of stroke onset. Patients were categorized on the basis of vascular occlusion, as shown on MR angiography. Lesion volumes were determined by using manual delineation (ADC(man)) and a threshold method for ADC values (<550 x 10(-9) mm(2)/s(-1), ADC(<550)). Infarct volumes were analyzed by using T2-weighted (n = 109) or CT (n = 11) images obtained on days 5-8. RESULTS: Median lesion volumes for ADC(<550), ADC(man), and infarcts, respectively, were as follows: proximal internal carotid artery (ICA)/middle cerebral artery (MCA) occlusions, 10, 23, and 32 cm(3); carotid-T occlusions, 11, 37, and 138 cm(3); MCA trunk occlusions, 11, 27, and 44 cm(3)); and MCA branch occlusions 8, 27, and 21 cm(3). Initial ADC lesion volumes were different only between the carotid T and the MCA branch (P < .05). On days 5-8, infarct volumes decreased from proximal to distal sites (P < .05), with the exception of MCA trunk versus proximal ICA/MCA occlusions. Recanalization rate in carotid-T occlusion was significantly lower than those of all other occlusion types. CONCLUSION: Initial ADC lesions can be small, even in patients with proximal vascular occlusions. These patients develop considerably large infarctions, suggesting a high potential for infarct growth. This growth might be averted with improved early recanalization of proximal vascular occlusions.

The medical treatment of patients with Parkinson's disease receiving subthalamic neurostimulation.

INTRODUCTION: Deep brain stimulation of subthalamic nucleus (STN-DBS) for Parkinson's disease allows for a reduction in medication dosage. Changes in total levodopa equivalent daily dose (LEDD) have been frequently reported, there is little information about changes within the drug classes. METHODS: We retrospectively assessed the changes in antiparkinsonian drugs dosages in 150 patients from one center who had preoperative and postoperative evaluations at 6 months and 3 years. Two long term subgroups with postoperative follow-up till the 5th-6th year (n = 58) and 10th year (n = 15) were included. RESULTS: The major modifications in medication dosage occurred during the initial postoperative period. LEDD was reduced by 53.4% compared to baseline at 6 months and 47.9% at 3 years. Fifty six percent and 41.3% of the patients were on monotherapy, 9.3% on no medication at 6 months and 6.7% at 3 years post surgery. Patients on levodopa, or dopamine agonists showed similar reductions. At the 3rd year the oldest group of patients showed a significant decrease in dopamine agonists. The number of patients treated with amantadine was significantly reduced; however the number of patients treated with antidepressants was significantly increased over the first 3 years. Annual medication costs per patient were decreased after the DBS-STN implantation by 61.3% at 6 months and 55.4% at 3 years. CONCLUSION: STN-DBS allows for a reduction in the dosage of medication and the costs are similarly reduced. In this cohort different medication groups were reduced to a similar extent. Patients' demographic factors did not play a major role in the selection of treatment.

Testing for alcohol sensitivity of tremor amplitude in a large cohort with essential tremor.

BACKGROUND: Improvement of essential tremor (ET) amplitude after alcohol ingestion is usually based on patient reports but a quantitative test for large numbers of patients is lacking and the percentage of ET patients with a detectable alcohol effect is therefore unknown. METHODS: A validated and published alcohol home test was used in 104 ET patients. The Archimedes spiral was drawn before alcohol ingestion and at 4 time points after alcohol consumption and rated on a 10-point rating scale according to Bain and Findley. A second identical test without alcohol ingestion was performed by the same patients and evaluated by the same two raters to analyze the total variability of the spiral ratings. RESULTS: Alcohol reduces tremor in ET patients as a group and a rebound effect with an increase in tremor intensity was found the next morning. Sex, family history of ET, diagnosis (definite vs. probable) and medical history of alcohol responsiveness do not predict the alcohol response. The minimal detectable difference in the spiral score was 2 due to spontaneous tremor fluctuations and inter-rater differences. The test demonstrated alcohol sensitivity of the tremor in 46% of the patients. Responsivity to alcohol could only be seen in patients with spiral scores above 3. CONCLUSIONS: Alcohol sensitivity is a feature of ET in at least 46% of the patients. We could not find predictors for alcohol sensitivity. The minimal detectable change is 2 scores and alcohol responsivity was only detected in patients with baseline Archimedes spiral rating of ≥3.

Are there time-dependent differences in diffusion and perfusion within the first 6 hours after stroke onset?

BACKGROUND AND PURPOSE: Stroke heterogeneity in computed tomography-based studies has been attributed as main cause for missing efficacy of intravenous tissue plasminogen activator (tPA) therapy within 3 to 6 hours. We investigated early time-dependent differences in acute stroke pathophysiology by multiparametric magnetic resonance imaging (MRI). METHODS: Stroke MRI of 112 acute ischemic stroke patients within <6 hours were dichotomized into a <3-hour group (n=52) and a 3- to 6-hour group (n=60). Infarct volume was determined on days 5 to 8. Lesion volumes were determined for apparent diffusion coefficient (ADC_man) and the subregion with ADC values <550x10(-9) mm/s2 (ADC <550), and for the time-to-peak (TTP) delay of 2 to 4 seconds, 4 to 6 seconds, 6 to 8 seconds, and >8 seconds. A subsample analysis was performed for occlusions of the middle carotid artery (MCA) trunk (n=36) and MCA branches (n=30), and for all patients treated by intravenous tPA (n=70). RESULTS: ADC and TTP lesion volumes were not different within <3 hours compared with volumes at 3 to 6 hours. In patients receiving intravenous tPA (n=70), there were no significant differences in ADC_man, TTP >2 seconds, and infarct volume (days 5 to 8) between the 2 groups. There was a greater proportion of ADC <550/ADC_man, which was most pronounced in patients with MCA trunk occlusions after 3 to 6 hours and a larger mismatch in the <3-hour group compared with that of the 3- to 6-hour group. In MCA branch occlusions, there was a less severe TTP delay after 3 to 6 hours. However, all differences missed the significance level (P=0.05) after correction for multiple testing. CONCLUSIONS: We observed no significant time-dependent differences within 6 hours after stroke onset in degree and volume of diffusion and perfusion impairment. An exclusion from intravenous tPA solely based on a rigid 3-hour time window seems unjustified in MRI-confirmed ischemic stroke.

Predictors of apparent diffusion coefficient normalization in stroke patients.

BACKGROUND AND PURPOSE: We sought to describe the frequency of normalization of apparent diffusion coefficient (ADC) values that are decreased in hyperacute stroke and to identify characteristics of tissue demonstrating normalization. METHODS: Sixty-eight acute ischemic stroke patients underwent MRI examination (including diffusion/perfusion imaging and MR angiography) within 6 hours (mean, 2.8 hours) after symptom onset, after 24 hours, and again 4 to 7 days later. Lesion volumes with decreased ADC and delayed time to peak in perfusion imaging were determined. In patients showing ADC normalization, volumes with ADC decrease graded as <50%, 50% to 60%, 60% to 70%, and 70% to 80% of the contralateral value were determined by thresholding. Patients were categorized as normalizers (demonstrating ADC normalization in >5 mL tissue with initially decreased ADC) or nonnormalizers (demonstrating ADC normalization in <5 mL tissue). RESULTS: Fourteen patients (19.7%) were classified as normalizers. Eleven of 31 patients (35.5%) initially imaged <3 hours after stroke onset and 3 of 37 (7.5%) of those imaged 3 to 6 hours after onset were normalizers. ADC normalization occurred predominantly in the basal ganglia and white matter after thrombolytic therapy in patients with more distal vessel occlusions. All normalizers demonstrated at least partial tissue reperfusion. Tissue with more severe initial decrease in ADC was less likely to demonstrate normalization. CONCLUSIONS: ADC normalization is not a rare event in acute stroke after tissue reperfusion. Brain tissue with initially decreased ADC, especially within 3 hours after stroke onset, may include "tissue at risk."

The impact of age and disease duration on the long term outcome of neurostimulation of the subthalamic nucleus.

BACKGROUND: Selection of patients with Parkinson's disease for neurostimulation of subthalamic nucleus (STN-DBS) is still poorly studied. AIM: To identify the impact of age and disease duration on the outcome of bilateral STN-DBS. METHODS: 110 operated patients in a single center covering a large range of age and disease duration were retrospectively included and followed for up-to 5 years. Standardized UPDRS assessments were obtained at 0.5-1 and 3-5 years. Patients were stratified into three age groups (≤ 55, 56-64 and ≥ 65 years) and the middle age group was further stratified into 2 disease duration subgroups (<15 years, ≥ 15 years). RESULTS: The age groups had comparable baseline data except for the predefined differences. Compared to baseline early and late intra-group "Med Off-Stim On" motor scores were significantly improved for all groups (p < 0.001). Mood/cognition were significantly improved in younger two groups (p = 0.008, 0.019) at 0.5-1 year. Inter-group comparisons showed significantly worse early and late axial scores for older patients (p < 0.05). All groups had comparable postoperative improvement except for the older group which had significantly less improvement of early UPDRS-II, late UPDRS-I, and early and late PIGD/axial scores. Different disease durations had no effect on the outcome except for worse Schwab and England Off-score in longer duration group (p = 0.02). Side effects of surgery and long-term management were similar. CONCLUSION: STN-DBS is an efficient treatment of advanced PD for all treated age-groups. Provided strict inclusion criteria are respected, older age and longer disease duration are associated with slightly worse effects mainly on L-dopa-resistant symptoms.

Motor outcome of dystonic camptocormia treated with pallidal neurostimulation.

BACKGROUND: Deep brain stimulation of the internal pallidum (GPi-DBS) is effective for various types of drug-refractory primary dystonias. Rare clinical forms as dystonic camptocormia may profit but available data are scarce. METHODS: We here report on a retrospective clinical assessment of three patients with primary dystonic camptocormia treated with GPi-DBS. RESULTS: All three patients showed marked response to bilateral GPi-DBS within days to weeks after surgery which was preserved in the long-term (38-45 months after implantation: mean improvement 82% as rated on the Burke Fahn Marsden Dystonia Rating Scale, 89% in the subitem "trunk"). Two patients developed mild stimulation induced speech problems (stuttering or dysarthria) which resolved with reprogramming or were acceptable in return for the control of dystonic symptoms. CONCLUSIONS: The diagnosis and treatment of camptocormia will continue to require expert knowledge in movement and neuromuscular disorders, but DBS may expand treatment options in this difficult patient population.

Stimulation of the subthalamic nucleus at an earlier disease stage of Parkinson's disease: concept and standards of the EARLYSTIM-study.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for advanced Parkinson's disease (PD) with disabling motor complications. However, stimulation may be beneficial at an earlier stage of PD when motor fluctuations and dyskinesia are only mild and psychosocial competence is still maintained. The EARLYSTIM trial was conducted in patients with recent onset of levodopa-induced motor complications (≤ 3 years) whose social and occupational functioning remained preserved. This is called 'early' here. The study was a randomized, multicenter, bi-national pivotal trial with a 2 year observation period. Quality of life was the main outcome measure, and a video-based motor score was a blinded secondary outcome of the study. Motor, neuropsychological, psychiatric and psychosocial aspects were captured by established scales and questionnaires. The patient group randomized here is the earliest in the disease course and the youngest recruited in controlled DBS trials so far. The methodological innovation for DBS-studies of this study lies in novel procedures developed and used for monitoring best medical treatment, neurosurgical consistency, best management of stimulation programming, blinded video assessment of motor disability, and prevention of suicidal behaviors.

A case of Rasmussen encephalitis treated with rituximab.

BACKGROUND: A 20-year-old woman was referred to our intensive care unit with a high frequency (every 1-2 min) of focal motor seizures. She had been diagnosed as having biopsy-proven Rasmussen encephalitis (RE) of the right hemisphere 7 years previously, since when she had been treated with numerous antiepileptic drugs, as well as with continuous immunotherapies, such as tacrolimus, corticosteroids, mycophenolate mofetil, intravenous immunoglobulin and immunoadsorption. Although hemispherectomy had been avoided due to slow progression of RE, she had not been seizure-free for more than 7 weeks since diagnosis. INVESTIGATIONS: EEG and MRI. DIAGNOSIS: Focal motor status epilepticus associated with right hemispheric RE, causing continuous epileptic activity and unilateral atrophy with edema in the right hemisphere. MANAGEMENT: Immunoadsorption was used initially to treat the seizures. Once they had ceased, we used 375 mg/m2 intravenous rituximab--a monoclonal anti-CD20 antibody--once-weekly for 4 weeks to stabilize the condition, leading to complete depletion of CD19+ B cells. Rituximab infusions were used again when concentrations of CD19+ B cells rose and focal seizures re-emerged. The patient remained on antiepileptic therapy (levetiracetam, oxcarbazepine, zonisamide and phenobarbital) throughout treatment.