Pulse duration settings in subthalamic stimulation for Parkinson's disease.

BACKGROUND: Stimulation parameters in deep brain stimulation (DBS) of the subthalamic nucleus for Parkinson's disease (PD) are rarely tested in double-blind conditions. Evidence-based recommendations on optimal stimulator settings are needed. Results from the CUSTOM-DBS study are reported, comparing 2 pulse durations. METHODS: A total of 15 patients were programmed using a pulse width of 30 µs (test) or 60 µs (control). Efficacy and side-effect thresholds and unified PD rating scale (UPDRS) III were measured in meds-off (primary outcome). The therapeutic window was the difference between patients' efficacy and side effect thresholds. RESULTS: The therapeutic window was significantly larger at 30 µs than 60 µs (P = ·0009) and the efficacy (UPDRS III score) was noninferior (P = .00008). INTERPRETATION: Subthalamic neurostimulation at 30 µs versus 60 µs pulse width is equally effective on PD motor signs, is more energy efficient, and has less likelihood of stimulation-related side effects. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Functional Connectivity Differences of the Subthalamic Nucleus Related to Parkinson's Disease.

A typical feature of Parkinson's disease (PD) is pathological activity in the subthalamic nucleus (STN). Here, we tested whether in patients with PD under dopaminergic treatment functional connectivity of the STN differs from healthy controls (HC) and whether some brain regions show (anti-) correlations between functional connectivity with STN and motor symptoms. We used functional magnetic resonance imaging to investigate whole-brain resting-state functional connectivity with STN in 54 patients with PD and 55 HC matched for age, gender, and within-scanner motion. Compared to HC, we found attenuated negative STN-coupling with Crus I of the right cerebellum and with right ventromedial prefrontal regions in patients with PD. Furthermore, we observed enhanced negative STN-coupling with bilateral intraparietal sulcus/superior parietal cortex, right sensorimotor, right premotor, and left visual cortex compared to HC. Finally, we found a decline in positive STN-coupling with the left insula related to severity of motor symptoms and a decline of inter-hemispheric functional connectivity between left and right STN with progression of PD-related motor symptoms. Motor symptom related uncoupling of the insula, a key region in the saliency network and for executive function, from the STN might be associated with well-known executive dysfunction in PD. Moreover, uncoupling between insula and STN might also induce an insufficient setting of thresholds for the discrimination between relevant and irrelevant salient environmental stimuli, explaining observations of disturbed response control in PD. In sum, motor symptoms in PD are associated with a reduced coupling between STN and a key region for executive function.

FP-CIT- and IBZM-SPECT in Corticobasal Syndrome: Results from a Clinical Follow-Up Study.

OBJECTIVE: To evaluate the striatal presynaptic dopamine transporter (FP-CIT-SPECT) and postsynaptic D2 receptor (IBZM-SPECT) binding in patients with corticobasal syndrome (CBS). BACKGROUND: FP-CIT and IBZM are commercially available and approved SPECT tracers for in vivo molecular imaging of pre- and postsynaptic nigrostriatal neuronal degeneration, but only few data for CBS are available. METHODS: 23 patients meeting clinical criteria for early- to mid-stage CBS (disease duration ≤4 years) were examined with SPECT radiotracers FP-CIT and IBZM. All suspected CBS patients underwent a clinical follow-up examination and were re-evaluated after 19.7 ± 15.2 months (mean ± SD). Postmortem diagnosis was available for 2 patients. In patients who met research criteria for probable CBS at the final follow-up visit (n = 19; disease duration: 1.95 ± 0.91 years), SPECT binding values were compared to those of age- and gender-matched Parkinson's disease (PD) patients (n = 18, disease duration: 1.92 ± 0.91 years; clinical follow-up: 32 ± 29.6 months) and neurologically normal control subjects (n = 19). RESULTS: In comparison to the healthy control subjects, both patient groups showed significant and asymmetric reduction of the striatal presynaptic dopamine transporter binding, but PD patients had significantly lower FP-CIT binding ratios than probable-CBS patients. FP-CIT binding values of probable-CBS patients and healthy controls demonstrated marked overlaps, and in 7 patients (39%) scans revealed no dopaminergic deficit. IBZM uptake did not show significant between-group differences. CONCLUSION: Our data indicate that in the early- to mid-stage CBS the degree of nigrostriatal impairment is only mild with a significant proportion of preserved dopamine transporter binding.

Associated aneurysms in supratentorial arteriovenous malformations: impact of aneurysm size on haemorrhage.

BACKGROUND: Associated aneurysms (AAs) are presumed to represent an additional risk factor for intracranial haemorrhage from cerebral arterio-venous malformations (AVMs). To date, efforts to capture their natural history, as well as to identify aneurysms with the potential capability of regression after AVM treatment remain incomprehensive. As the aneurysm size represents an important aspect for the treatment indication of incidental saccular aneurysms, this factor has rarely been encountered for the treatment of AAs so far. The present study aims to determine the angiographic and clinical characteristics of AAs with special focus on aneurysm size and their consequences for treatment. METHODS: Patients with cerebral AVMs, treated in our department between 1990 and 2013, were analyzed retrospectively. Only patients with supratentorial AVMs and flow-related AAs of the feeding arteries were evaluated. Thus, patients harboring AVMs of the cerebellum and the brain stem and patients with intranidal, venous or remote aneurysms were excluded. Treatment strategies were assessed with special attention on bleeding source and on AA size. RESULTS: In 59 of 409 patients (14%) with supratentorial AVMs, a total of 85 AAs of the feeding arteries were identified. 14 of 59 individuals (24%) presented with multiple AAs. Of 85 AA, 58 aneurysms (68%) were classified as proximal and 27 aneurysms (32%) as distal. The most common location of AAs was the middle cerebral artery (MCA, 39%), followed by the internal carotid artery (ICA, 27%) and the anterior cerebral artery (ACA, 21%). The mean AA size was 4.4 mm ± 3.4 mm. Intracranial haemorrhage was found in 21 of 59 patients (36%) with coexisting AAs. Among these, 10 individuals (17%) suffered from rupture of an AA, accounting for nearly half of all bleedings in this subgroup. Among those patients bearing a single AA, the size of ruptured aneurysms differed significantly from those unruptured (6.6 mm vs. 4.4 mm, p = 0.0046). Nineteen patients (32%) received treatment of 22 AAs, whereas sole AVM treatment was adopted in 26 patients (44%) and conservative management in 14 patients (24%). The main reasons to leave AAs untreated were the small AA size (<5 mm), poor clinical state or treatment denial by the patients. CONCLUSIONS: The aneurysm size of AAs in AVM influences the risk of haemorrhage. Therefore, the treatment of larger (diameter ≥5 mm) AAs should be considered, even if a treatment indication of the associated AVM is not given.

Posterior fossa arterio-venous malformations: current multimodal treatment strategies and results.

The present study aimed to determine the clinical presentation, the multimodal interdisciplinary treatment strategies and outcome of posterior fossa arterio-venous malformations (AVMs) in our neurovascular centre. Fifty-three patients with a posterior fossa AVM were seen between 1998 and 2012 and analysed retrospectively. Patients were either managed conservatively or treated with endovascular, microsurgical or radiosurgical procedures or in combination. Thirty-nine patients (74 %) presented with intracranial haemorrhage and 14 patients (26 %) with unspecific symptoms. In 22 cases with haemorrhage (56 %), an intracerebellar haematoma was found, whereas 17 patients (44 %) suffered from subarachnoid haemorrhage. AVMs were located in the cerebellum in 44 patients (83 %), in the brainstem in four patients (7.5 %) and the cerebello-pontine angle in another four individuals (7.5 %). Forty-two patients (79 %) were treated either by emboliziation (n = 12, 29 %), surgical resection (n = 16, 38 %), surgical resection with preoperative embolization (n = 12, 29 %) or radiotherapy alone (n = 2, 4 %). A total of eleven patients did not receive any treatment (21 %). Both, morbidity and mortality related to treatment were 12 %, whereas overall morbidity and mortality was 26 and 15 %, respectively. Complete AVM elimination was achieved in 81 % of the treated lesions. A multimodal treatment sequence nowadays represents the gold standard for posterior fossa AVMs. Patients are at high risk for morbidity and mortality, due to the impact of haemorrhage and treatment. Therefore, treatment has to be thoroughly indicated, especially for those patients without bleeding. The initial neurological condition seems to be crucial in terms of clinical outcome.

Brain volume patterns in corticobasal syndrome versus idiopathic Parkinson's disease.

BACKGROUND AND PURPOSE: Patients with a corticobasal syndrome (CBS) present a rare form of atypical parkinsonism characterized by asymmetric clinical symptoms and progressive motor and nonmotor impairment, such as apraxia, alien limb phenomenon, aphasia, myoclonus, dystonia, and cognitive impairment. At early stages, clinical differentiation between CBS and idiopathic Parkinson's disease (IPD) can be challenging. METHODS: Using high-resolution T1-weighted images and voxel-based morphometry (VBM), we sought to identify disease-specific patterns of brain atrophy in a small sample of CBS and IPD patients at early stages of disease. We acquired MR images of 17 patients diagnosed with CBS and compared them with MR images of 17 subjects affected by IPD. Images were preprocessed and analyzed using VBM. RESULTS: When compared to each other, the CBS and IPD patients of our cohort showed differences in regional gray and white matter volume depending on the diagnosis, specifically in the superior longitudinal fascicle. CONCLUSIONS: In our small patients' group, VBM was able to detect changes in regional gray and white matter volume between patients affected by CBS and patients with IPD as early as 1.5-2 years after the onset of the first motor symptoms.

Long-term adherence and response to botulinum toxin in different indications.

OBJECTIVE: The objective of the study was the analysis of adherence and self-perceived treatment response to long-term botulinum neurotoxin type A (BoNT-A) treatment in different neurological indications. METHODS: In this retrospective, monocentric, observational study, cross-sectional and longitudinal data of 1351 patients documenting 20705 injection appointments at the BoNT outpatient clinic of Heinrich Heine University Duesseldorf between 1989 and 2014 were retrospectively analyzed. Patients had been treated with BoNT for neurological conditions, including cervical dystonia (CD), blepharospasm (BSP), other dystonia (ODT), hemifacial spasm (HFS), and spasticity (SPAS). The parameters longitudinally analyzed for the entire cohort were therapy duration as well as the mean and cumulative BoNT-A dose. Cross-sectionally, for subgroups of at least 721, patients' global self-perceived quality of health and life, global self-perceived reduction of symptoms by BoNT-A treatment as well as the clinical global impression were evaluated. Furthermore, mouse hemidiaphragm assay antibodies (MHDA-ABs) were analyzed in a subgroup. RESULTS: The mean treatment duration was 4.58 years (95% CI 4.32-4.84), and 678 (50.2%) therapy dropouts of 1351 patients occurred within the first 8 years. Therapy adherence and self-perceived symptom reduction in long-term BoNT-A treatment over the years were significantly longer in BSP, HFS, and CD patients than in ODT and SPAS patients. INTERPRETATION: The treatment indication determines long-term adherence and self-perceived symptom reduction in BoNT-A therapy, which are better in BSP, HFS, and CD patients than in ODT and SPAS patients. MHDA-ABs had a significant impact on global self-perceived symptom reduction, but with only a limited degree.

Somatosensory area 3b is selectively unaffected in corticobasal syndrome: combining MRI and histology.

An increasing number of neuroimaging studies addressing patients with corticobasal syndrome use macroscopic definitions of brain regions. As a closer link to functionally relevant units, we aimed at identifying magnetic resonance-based atrophy patterns in regions defined by probability maps of cortical microstructure. For this purpose, three analyses were conducted: (1) Whole-brain cortical thickness was compared between 36 patients with corticobasal syndrome and 24 controls. A pattern of pericentral atrophy was found, covering primary motor area 4, premotor area 6, and primary somatosensory areas 1, 2, and 3a. Within the central region, only area 3b was without atrophy. (2) In 18 patients, longitudinal measures with follow-ups of up to 59 months (mean 21.3 ± 15.4) were analyzed. Areas 1, 2, and 6 showed significantly faster atrophy rates than primary somatosensory area 3b. (3) In an individual autopsy case, longitudinal in vivo morphometry and postmortem pathohistology were conducted. The rate of magnetic resonance-based atrophy was significantly correlated with tufted-astrocyte load in those cytoarchitectonically defined regions also seen in the group study, with area 3b being selectively unaffected.

Less is more - Pulse width dependent therapeutic window in deep brain stimulation for essential tremor.

BACKGROUND: Shorter pulse widths than conventional pulse width settings may lead to reduction of side effects and therefore be a valuable therapeutic option for deep brain stimulation (DBS) in patients with essential tremor (ET). OBJECTIVE: To compare the DBS effect of shorter pulse width at 40 µs (DBS-40 µs) to conventional pulse width at 60 µs (DBS-60 µs) on the therapeutic window in ET patients. METHODS: For this prospective, randomized, double-blind, crossover study 9 ET patients with chronic DBS of the ventral intermediate nucleus (VIM)/posterior subthalamic area (PSA) were recruited. Therapeutic window was calculated by determining efficacy and side effect thresholds for DBS-40 µs and DBS-60 µs. Tremor Rating Scales and Kinesia tremor analyses were used to compare clinical efficacy between the considered settings and deactivated DBS (DBS-OFF). Volume of neural activation (VNA) was calculated for both efficacy and side effect thresholds at each pulse width. RESULTS: DBS-40 µs showed a significantly larger therapeutic window than DBS-60 µs mainly due to higher side-effect thresholds. Both conditions significantly improved tremor compared to DBS-OFF, while efficacy was comparable between DBS-40 µs and DBS-60 µs. Moreover, VNA at efficacy threshold was smaller and less energy was required for tremor suppression with DBS-40 µs compared to DBS-60 µs. CONCLUSIONS: VIM/PSA-DBS with short pulse width represents a promising programming option for DBS in ET as it reduces side effects while maintaining efficient tremor suppression. Furthermore, our data support the notion of pulse width dependent selective modulation of distinct fiber tracts leading to widening of the therapeutic window.

The treatment of Parkinson's disease with deep brain stimulation: current issues.

Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients' mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.