•Mono-center trial investigating imaging data of exclusively patients with dystonia during childhood and adolescence.•Diffusion parameters differ between patients with acquired and inherited dystonia ...in several brain regions.•Higher fiber density between GPi and putamen of patients with acquired dystonia.
Background: Childhood-onset dystonia is often progressive and severely impairs a child´s life. The pathophysiology is very heterogeneous and treatment responses vary in patients with dystonia. Factors influencing treatment effects remain to be elucidated. We hypothesize that differences in brain connectivity and fiber coherence contribute to the heterogeneity in treatment response among pediatric patients with inherited and acquired dystonia.
Methods: Twenty patients with childhood-onset dystonia were retrospectively recruited including twelve patients with inherited or idiopathic, and eight patients with acquired dystonia (mean age 10 years; 8 female/12 male). Fiber density between the internal part of the globus pallidus and selective target regions, as well as the diffusion measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed and compared between different etiologies.
Results: Patients with acquired dystonia presented higher fiber density to the premotor cortex and putamen and lower FA values in the thalamus compared to patients with inherited/idiopathic dystonia. MD in the premotor cortex was higher in patients with acquired dystonia, while it was lower in the thalamus.
Conclusion: Diffusion MRI reveals microstructural and network alterations in patients with dystonia of different etiologies.
Purpose
Orientating the angle of directional leads for deep brain stimulation (DBS) in an axial plane introduces a new degree of freedom that is indicated by embedded anisotropic directional markers. ...Our aim was to develop algorithms to determine lead orientation angles from computed tomography (CT) and stereotactic x‐ray imaging using standard clinical protocols, and subsequently assess the accuracy of both methods.
Methods
In CT the anisotropic marker artifact was taken as a signature of the lead orientation angle and analyzed using discrete Fourier transform of circular intensity profiles. The orientation angle was determined from phase angles at a frequency 2/360° and corrected for aberrations at oblique leads. In x‐ray imaging, frontal and lateral images were registered to stereotactic space and sub‐images containing directional markers were extracted. These images were compared with projection images of an identically located virtual marker at different orientation angles. A similarity index was calculated and used to determine the lead orientation angle. Both methods were tested using epoxy phantoms containing directional leads (Cartesia™, Boston Scientific, Marlborough, USA) with known orientation. Anthropomorphic phantoms were used to compare both methods for DBS cases.
Results
Mean deviation between CT and x‐ray was 1.5° ± 3.6° (range: −2.3° to 7.9°) for epoxy phantoms and 3.6° ± 7.1° (range: −5.6° to 14.6°) for anthropomorphic phantoms. After correction for imperfections in the epoxy phantoms, the mean deviation from ground truth was 0.0° ± 5.0° (range: −12° to 14°) for x‐ray. For CT the results depended on the polar angle of the lead in the scanner. Mean deviation was −0.3° ± 1.9° (range: −4.6° to 6.6°) or 1.6° ± 8.9° (range: −23° to 34°) for polar angles ≤ 40° or > 40°.
Conclusions
The results show that both imaging modalities can be used to determine lead orientation angles with high accuracy. CT is superior to x‐ray imaging, but oblique leads (polar angle > 40°) show limited precision due to the current design of the directional marker.
•Proof that proximity to the dentatorubrothalamic tract (DRTT) is responsible for increased tremor suppression in deep brain stimulation (DBS) for essential tremor (ET).•High-quality prospective, ...randomized, double-blind clinical data from 13 ET subjects.•Population-based DRTTs using probabilistic tractography in state-of-the-art diffusion MRI data from the human connectome project with supplementary validation against clinical dMRI data from ET patients.•Implications for the future of direct DBS targeting in tremor patients.
To investigate the relation between deep brain stimulation (DBS) of the posterior-subthalamic-area (PSA) and the ventral-intermediate-nucleus (VIM) and the distance to the dentatorubrothalamic tract (DRTT) in essential tremor (ET).
Tremor rating scale (TRS) hemi-scores were analyzed in 13 ET patients, stimulated in both the VIM and the PSA in a randomized, crossover trial. Distances of PSA and VIM contacts to population-based DRTTs were calculated. The relationships between distance to DRTT and stimulation amplitude, as well as DBS efficiency (TRS improvement per amplitude) were investigated.
PSA contacts were closer to the DRTT (p = 0.019) and led to a greater improvement in TRS hemi-scores (p = 0.005) than VIM contacts. Proximity to the DRTT was related to lower amplitudes (p < 0.001) and higher DBS efficiency (p = 0.017).
Differences in tremor outcome and stimulation parameters between contacts in the PSA and the VIM can be explained by their different distance to the DRTT.
•Pediatric neuroimaging resources were assembled and implemented to assist deep brain stimulation imaging-based analyses.•Local sweetspot analysis was performed in a group of pediatric patients with ...dystonia treated with pallidal DBS.•Connectomic analysis was performed to demonstrate a distributed network correlate of DBS effect.
Deep brain stimulation (DBS) is an established treatment in patients of various ages with pharmaco-resistant neurological disorders. Surgical targeting and postoperative programming of DBS depend on the spatial location of the stimulating electrodes in relation to the surrounding anatomical structures, and on electrode connectivity to a specific distribution pattern within brain networks. Such information is usually collected using group-level analysis, which relies on the availability of normative imaging resources (atlases and connectomes). Analysis of DBS data in children with debilitating neurological disorders such as dystonia would benefit from such resources, especially given the developmental differences in neuroimaging data between adults and children. We assembled pediatric normative neuroimaging resources from open-access datasets in order to comply with age-related anatomical and functional differences in pediatric DBS populations. We illustrated their utility in a cohort of children with dystonia treated with pallidal DBS. We aimed to derive a local pallidal sweetspot and explore a connectivity fingerprint associated with pallidal stimulation to exemplify the utility of the assembled imaging resources.
An average pediatric brain template (the MNI brain template 4.5–18.5 years) was implemented and used to localize the DBS electrodes in 20 patients from the GEPESTIM registry cohort. A pediatric subcortical atlas, analogous to the DISTAL atlas known in DBS research, was also employed to highlight the anatomical structures of interest. A local pallidal sweetspot was modeled, and its degree of overlap with stimulation volumes was calculated as a correlate of individual clinical outcomes. Additionally, a pediatric functional connectome of 100 neurotypical subjects from the Consortium for Reliability and Reproducibility was built to allow network-based analyses and decipher a connectivity fingerprint responsible for the clinical improvements in our cohort.
We successfully implemented a pediatric neuroimaging dataset that will be made available for public use as a tool for DBS analyses. Overlap of stimulation volumes with the identified DBS-sweetspot model correlated significantly with improvement on a local spatial level (R = 0.46, permuted p = 0.019). The functional connectivity fingerprint of DBS outcomes was determined to be a network correlate of therapeutic pallidal stimulation in children with dystonia (R = 0.30, permuted p = 0.003).
Local sweetspot and distributed network models provide neuroanatomical substrates for DBS-associated clinical outcomes in dystonia using pediatric neuroimaging surrogate data. Implementation of this pediatric neuroimaging dataset might help to improve the practice and pave the road towards a personalized DBS-neuroimaging analyses in pediatric patients.
Directional deep brain stimulation (DBS) leads are now widely used, but the orientation of directional leads needs to be taken into account when relating DBS to neuroanatomy. Methods that can ...reliably and unambiguously determine the orientation of directional DBS leads are needed. In this study, we provide an enhanced algorithm that determines the orientation of directional DBS leads from postoperative CT scans. To resolve the ambiguity of symmetric CT artifacts, which in the past, limited the orientation detection to two possible solutions, we retrospectively evaluated four different methods in 150 Cartesia™ directional leads, for which the true solution was known from additional X-ray images. The method based on shifts of the center of mass (COM) of the directional marker compared to its expected geometric center correctly resolved the ambiguity in 100% of cases. In conclusion, the DiODe v2 algorithm provides an open-source, fully automated solution for determining the orientation of directional DBS leads.
The new essential tremor (ET) classification defined ET-plus (ET-p) as an ET subgroup with additional neurological signs besides action tremor. While deep brain stimulation (DBS) is effective in ET, ...there are no studies specifically addressing DBS effects in ET-p. 44 patients with medication-refractory ET and thalamic/subthalamic DBS implanted at our center were postoperatively classified into ET and ET-p according to preoperative documentation. Tremor suppression with DBS (stimulation ON vs. preoperative baseline and vs. stimulation OFF), measured via the Fahn-Tolosa-Marin tremor rating scale (TRS), stimulation parameters, and the location of active contacts were compared between patients classified as ET and ET-p. TRS scores at baseline were higher in ET-p. ET-p patients showed comparable tremor reduction as patients with ET, albeit higher stimulation parameters were needed in ET-p. Active electrode contacts were located more dorsally in ET-p of uncertain reason. Our data show that DBS is similarly effective in ET-p compared to ET. TRS scores were higher in ET-p preoperatively, and higher stimulation parameters were needed for tremor reduction compared to ET. The latter may be related to a more dorsal location of active electrode contacts in the ET-p group of this cohort. Prospective studies are warranted to investigate DBS in ET-p further.
This paper summarizes outcomes of a single-center study of intracavitary brachytherapy (IBT) with stereotactically applied phosphorus-32 (
32
P) colloid for treatment of cystic craniopharyngiomas. We ...assessed its efficacy and safety, on the basis of clinical and radiological outcomes in one of the largest reported patient series. Between 1992 and 2011, 53 patients were treated with IBT, 14 without previous treatment and 39 who had previously been treated for recurrent cysts. Intervention was performed by applying 200 Gy to the internal cyst wall (median volume 6.1 ml). Median clinical and radiological follow-up were 60.2 and 53.0 months, respectively. Actuarial tumor cyst control was 86.0 ± 5.3 % at 12, 24, and 60 months. Actuarial out-of-field control (development of new cysts or progression of solid tumor parts) was 90.9 ± 4.3, 84.0 ± 5.6, and 54.5 ± 8.8 % after 12, 24, and 60 months, respectively. Corresponding actuarial overall progression-free survival was 79.4 ± 6.1, 72.4 ± 6.8, and 45.6 ± 8.7 % at 12, 24, and 60 months, respectively. Visual function improved for 12 patients (23.5 %), remained unchanged for 34 patients (66.7 %), and worsened for five patients (9.8 %), correlating with tumor progression in each case. Endocrinological deterioration occurred for ten patients (19.6 %); for nine patients this was a result of tumor progression or after tumor resection and for one it was attributed to irradiation. Within six months of IBT seven patients (13.7 %) experienced transient neurological deficits and two patients (3.9 %) deteriorated permanently (hemiparesis and third nerve palsy). Stereotactically applied
32
P is highly efficacious for control of cystic components of craniopharyngiomas and is associated with a low risk of permanent morbidity. The procedure does not, however affect the development of new cysts or the progression of solid tumor parts.
To evaluate deep brain stimulation (DBS) of the posterior subthalamic area (PSA) in essential tremor (ET) and compare it to the ventral intermediate nucleus of the thalamus (VIM) in terms of ...stimulation efficacy, efficiency, and side effects.
DBS leads were implanted such that contacts were placed in the VIM, on the intercommissural line, and in the PSA. Thirteen patients with ET entered a randomized, double-blind crossover phase and completed a 1-year follow-up.
PSA-DBS significantly reduced tremor severity and improved quality of life. There were no relevant differences in quality and frequency of stimulation side effects between VIM and PSA, with a tendency toward greater tremor improvement with PSA stimulation. Clinical benefit was achieved at significantly lower stimulation amplitudes in the PSA. The majority of patients remained with PSA-DBS after 1 year.
In accordance with previous retrospective investigations, our prospective data suggest that PSA-DBS is at least equally effective as but possibly more efficient than VIM-DBS.
This study provides Class I evidence that for patients with essential tremor, PSA-DBS is not significantly different from VIM-DBS in suppressing tremor, but clinical benefit from PSA-DBS is attained at lower stimulation amplitudes.
Introduction: Neuromodulation using deep brain stimulation (DBS), spinal cord stimulation (SCS), and peripheral nerve field stimulation (PNFS) to treat neurological, psychiatric, and pain disorders ...is a rapidly growing field. Infections related to the implanted hardware are among the most common complications and result in health-related and economic burden. Unfortunately, conservative medical therapy is less likely to be successful. In this retrospective study, we aimed to identify characteristics of the infections and investigated surgical and antimicrobial treatments. Methods: A retrospective analysis was performed of patients with an infection related to DBS, SCS, and/or PNFS hardware over an 8-year period at our institution. Data were analyzed for type of neurostimulator, time of onset of infection following the neurosurgical procedure, location, and surgical treatment strategy. Surgical treatment of infections consisted of either a surgical wound revision without hardware removal or a surgical wound revision with partial or complete hardware removal. Data were further analyzed for the microorganisms involved, antimicrobial treatment and its duration, and clinical outcome. Results: Over an 8-year period, a total of 1,250 DBS, 1,835 SCS, and 731 PNFS surgeries were performed including de novo system implantations, implanted pulse generator (IPG) replacements, and revisions. We identified 82 patients with infections related to the neurostimulator hardware, representing an incidence of 3.09% of the procedures. Seventy-one percent of the patients had undergone multiple surgeries related to the neurostimulator prior to the infection. The infections occurred after a mean of 12.2 months after the initial surgery. The site of infection was most commonly around the IPG, especially in DBS and SCS. The majority (62.2%) was treated by surgical wound revision with simultaneous partial or complete removal of hardware. Microbiological specimens predominantly yielded Staphylococcus epidermidis (39.0%) and Staphylococcus aureus (35.4%). After surgery, antimicrobials were given for a mean of 3.4 weeks. The antimicrobial regime was significantly shorter in patients with hardware removal in comparison to those who only had undergone surgical wound revision. One intracranial abscess occurred. No cases of infection-related death, sepsis, bacteremia, or intraspinal abscesses were found. Conclusion: Our data did show the predominance of S. epidermidis and S. aureus as etiologic organisms in hardware-related infections. Infections associated with S. aureus most likely required (partial) hardware removal. Aggressive surgical treatment including hardware removal shortens the duration of antimicrobial treatment. Clear strategies should be developed to treat hardware-related infections to optimize patient management and reduce health- and economic-related burden.
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