Faculty Bibliography
Searched for:
Department/Unit:Neurology
Total Results:
24488
Isolated Cranial Tremors: A Reappraisal
Isolated cranial tremors (face tremor, jaw tremor, vocal tremor, and embouchure tremor) are unusual examples of focal tremor disorders. The etiology and treatment of these troublesome and occasionally disabling conditions deserve more attention. In this review, we summarize current knowledge about these disorders and consider their etiologies and treatment approaches. We suggest changes to the current classification system of isolated cranial tremors based on shared phenomenology and treatment response.
PMID: 42235526
ISSN: 1098-9021
CID: 6044132
Addressing the needs of nano-rare patients: the n-Lorem experience
Patients with extremely rare pathogenic variants pose unique challenges to current healthcare systems. Nano-rare mutations have been defined as mutations with a known prevalence of <30 patients worldwide, but because of the small fraction of humans who have undergone genetic testing, neither the precise prevalence of individual mutations nor the total prevalence of patients with nano-rare mutations is known. n-Lorem is a non-profit founded in 2020 with the mission of equitably discovering, developing, and providing bespoke experimental antisense oligonucleotides (ASOs) for free, for life, to patients with nano-rare mutations that are amenable to ASO treatment. In this perspective, we provide an overview of the n-Lorem processes and systems, the characteristics of the first 329 patients who have applied for treatment for whom initial assessment was completed and suitability for ASO treatment determined, and a summary of the results of ASO treatment for patients treated to date. Detailed data on individual patients and the overall clinical safety and tolerability profiles of the ASOs for which there are clinical data are the subjects of other manuscripts.
PMCID:13227102
PMID: 42227334
ISSN: 1362-4962
CID: 6043682
Add-on treatment with vinpocetine reduces seizure frequency and improves comorbidities in patients with loss-of-function γ-aminobutyric acid type A receptor variants
OBJECTIVE:receptor-related epilepsies. Here, we extend these observations with a retrospective observational study evaluating the response to vinpocetine in an additional seven patients. METHODS:Patients initiated treatment with vinpocetine between 2018 and 2025 at the Danish Epilepsy Centre or abroad. Clinical data were collected from medical records, seizure diaries, and neuropsychological assessments. The modulatory efficacy of vinpocetine was investigated using electrophysiological studies. RESULTS:receptor LoF variants were given add-on vinpocetine treatment. Electrophysiological analyses confirmed dose-dependent positive modulation by vinpocetine across tested variants. Six patients with a median age of 15.5 years (range = 6-29) continued treatment for a median of 24 months (range = 12-90), whereas three discontinued due to adverse effects (AEs) or lack of efficacy. The patients' level of function ranged from normal to moderate intellectual disability, psychiatric comorbidities, and behavioral disturbances. Four patients initiated vinpocetine due to uncontrolled seizures. One became seizure-free, and two experienced a 50%-55% reduction. Electroencephalograms demonstrated improved spike-wave indexes in four patients. Six showed improvement in nonseizure factors, and caregivers reported reduced aggressivity and better vocabulary in one. Vinpocetine was well tolerated, with only mild and reversible AEs reported. SIGNIFICANCE/CONCLUSIONS:receptor-related epilepsies, which should be investigated further in future N-of-1 trials.
PMID: 42227896
ISSN: 1528-1167
CID: 6043692
An examination of the influence of prefrontal cortical brain stimulation on sexual decision making
The goal of this study was to clarify the contribution of prefrontal cortex activity to men's appraisals, affect states, and decision making in the context of hypothetical heterosexual dating scenarios lacking clear consent. Transcranial direct stimulation (tDCS) was applied to the prefrontal cortex to examine whether it would modify and reduce the likelihood of hypothetical dating violence. Participants (n = 102) responded to first-person vignettes wherein a woman responded either ambiguously or with a refusal to their sexual advance. While responding to the vignettes, participants received sham or active tDCS to modulate prefrontal cortex-mediated responding. Neuromodulation interacted with the communication response type of the woman in the vignette (e.g. ambiguous vs. refusal responses) to influence participants' reports of negative affect (F = 9.57, P = 0.002, Cohen's f2
PMCID:13225266
PMID: 42232253
ISSN: 2753-149x
CID: 6043932
Perspective/short review: Adverse events associated with placement of spinal cord stimulators (SCS)
BACKGROUND/UNASSIGNED:The placement of Spinal Cord Stimulator (SCS) trial or permanent electrodes carries a 31.9-43% morbidity/adverse event (AE) rate. Most AEs are attributed to electrode migration (EM: device-related AE 26.7% older cohort vs. 9.7% newer cohort), spinal epidural hematomas (SEHs: 0.81-2.6%), infection (3.4% older vs. 1.9% recent cohort), SCI (spinal cord injury: percutaneous 0.45% vs. 0.36% paddle electrodes), dural tears (DT/ cerebrospinal fluid leaks (CSF leaks)), foreign body/fibrous reactions, or syrinx formation. METHODS/UNASSIGNED:SCSs are typically applied to address chronic neuropathic pain syndromes. Here, we evaluated 20 articles focusing on patients who developed postoperative myelopathy/radiculopathy, variously attributed to MR-documented AE warranting medical or surgical intervention. RESULTS/UNASSIGNED:Postoperative symptoms/signs of AE typically included the acute development of new/increased weakness, sensory loss, and/or sphincter dysfunction. Requisite STAT MR scans usually confirmed the etiology of AE including electrode migration, SEH, DT, SCI, and/or postoperative scarring/fibrosis. Most patients warranted STAT surgery, while a small subset could be managed conservatively. CONCLUSION/UNASSIGNED:The AE rate for spinal cord stimulators ranges from 31.9 to 43%. While the majority are due to electrode migration, other etiologies include SEH, SCI, DT, and foreign body reactions. Those who become acutely myelopathic usually warrant STAT MR scans with the majority additionally necessitating STAT surgical intervention to limit short/long-term neurological morbidity.
PMCID:13224183
PMID: 42232442
ISSN: 2229-5097
CID: 6043962
Subthalamic versus Posterior Subthalamic Stimulation for Optimal Tremor Control in Parkinson's Disease
UNLABELLED:<p>Introduction: Tremor-predominant Parkinson's disease (TPPD) generally responds favorably to deep brain stimulation (DBS) targeting the subthalamic nucleus (STN). However, traditional stereotactic targeting of the STN does not universally yield the anticipated intraoperative improvement, prompting exploration of additional targets to achieve optimal results prior to permanent implantation of electrodes. The posterior subthalamic area (PSA), including the caudal zona incerta (cZI), have been associated with tremor suppression and can be easily compared to the neighboring STN intraoperatively. METHODS:We retrospectively compared intraoperative and clinical outcomes in tremor-dominant PD patients who prospectively underwent dual trajectory microelectrode monitor targeting the STN and PSA/cZI. We compared the neurophysiology and tremor response of both the central (STN) and posterior (PSA) trajectories in 22 patients and analyzed outcomes in those who ultimately received traditional STN (16) or PSA/cZI lead implantation (12). RESULTS:While both groups achieved substantial overall motor improvement under chronic stimulation, intraoperative test stimulation through the posterior path produced more consistent tremor arrest compared with STN. These findings suggest that positioning the DBS lead further posteriorly to engage the PSA can augment tremor suppression in select cases of TPPD without compromising other parkinsonian symptom relief. CONCLUSION/CONCLUSIONS:Our results emphasize the value of intraoperative physiological feedback in trajectory selection in tremor-predominant patients and are consistent with emerging literature that PSA/cZI DBS is an effective and potentially superior target for management of tremor in PD. </p>.
PMCID:12810967
PMID: 41411220
ISSN: 1423-0372
CID: 6043352
On-site exposure to clinical epilepsy practice for experimental scientists engaged in epilepsy research: A pilot study by the ILAE commission on neurobiology
Educational initiatives that address the gap between basic/preclinical and clinical practices are important to effectively translate basic science discoveries to benefit patients. The ILAE Neurobiology Commission conducted a pilot project aimed at exposing basic and preclinical scientists engaged in epilepsy research to general clinical issues pertaining to the diagnosis and care of people with epilepsy. This aim was addressed through a two-week-long, on-site clinical training program for 50 basic scientists in 21 epilepsy centers across 18 countries in the six ILAE regions (with a maximum of 3 basic scientists per center). The learning objectives and the training module were discussed and defined by the project organizing committee, which consisted of Neurobiology Commission members and a team of epileptologists representing different geographical regions. The training activities were conducted at each epilepsy center under the local supervision of clinical tutors. Each basic scientist was exposed to 50.3 ± 23.3 (range 16-89) hours of intensive and dedicated clinical training, coordinated by 2-3 tutors per center, assisted by 6.8 ± 3.6 colleagues. A structured test consisting of 17 general clinical epilepsy questions was completed by the trainees before and after the training activity. The learning assessment was based on the comparison between responses to the exit and entry tests. After the on-site clinical exposure, the proportion of correct answers increased to 87% compared to 61% in the entry test. Structured post-training questionnaires demonstrated very high satisfaction of trainees and all involved tutors across the different aspects of the training module. This global pilot study demonstrated that on-site attendance by basic scientists in specialized clinical settings up-scaled their knowledge of clinical epileptology and facilitated networking with clinicians. Expansion of this pilot to further centers should be considered to understand how exposure to clinical practice affects research direction and quality of translational epilepsy research. PLAIN LANGUAGE SUMMARY: Epilepsy research has long benefitted from collaboration between scientists and clinicians. Early exposure of researchers to people with epilepsy and their care teams may strengthen future impact. This pilot study tested a two-week immersive experience where small teams of basic scientists shadowed clinicians during their work at hospitals around the world. Questionnaires showed high satisfaction among both groups. Results support expanding such training, with the backing of the International League Against epilepsy and aligned centers, to build understanding, interest, and long-term commitment, ensuring bench research is informed by and translates to clinical practice and improved quality of life for patients.
PMID: 42220231
ISSN: 2470-9239
CID: 6043402
Investigating the analytical robustness of the social and behavioural sciences
The same dataset can be analysed in different justifiable ways to answer the same research question, potentially challenging the robustness of empirical science1-3. In this crowd initiative, we investigated the degree to which research findings in the social and behavioural sciences are contingent on analysts' choices. We examined a stratified random sample of 100 studies published between 2009 and 2018, in which, for one claim per study, at least five reanalysts independently reanalysed the original data. The statistical appropriateness of the reanalyses was assessed in peer evaluations, and the robustness indicators were inspected along a range of research characteristics and study designs. We found that 34% of the independent reanalyses yielded the same result (within a tolerance region of ±0.05 Cohen's d) as the original report; with a four times broader tolerance region, this indicator increased to 57%. Of the reanalyses conducted, 74% reached the same conclusion as the original investigation, 24% yielded no effects or inconclusive results and 2% reported the opposite effect. This exploratory study indicates that the common single-path analyses in social and behavioural research should not be simply assumed to be robust to alternative analyses4. Therefore, we recommend the development and use of practices to explore and communicate this neglected source of uncertainty.
PMID: 41922703
ISSN: 1476-4687
CID: 6041172
Hemispherotomy for Drug-Resistant Epilepsy in a Low-Resource Setting: Surgical Outcomes and Quality of Life in 23 Children Treated in a Hybrid Program in Panama
INTRODUCTION/BACKGROUND:Hemispherotomy is an effective treatment for children with drug-resistant epilepsy (DRE). While hemispherotomy techniques and indications have evolved, access remains predominantly constrained to high-resource settings. METHODS:We performed a retrospective analysis of children who underwent hemispherotomy from 2011 to 2023 by a hybrid team, including local Panamanian and US neurologists, neurosurgeons, and EEG technicians and analyzed surgical, epilepsy, and quality of life (QoL) parameters. Follow-up data were collected according to the International Consortium for Health Outcomes Measurement (ICHOM) guidelines for children with epilepsy. RESULTS:Twenty-three children underwent hemispherotomy. The median age at surgery was 10 years (range 2-20). The median follow-up time was 6 years (range 1-13). The etiology of DRE included malformations of cortical development in 14 children (60.8%), including 8 (34.8%) with schizencephaly, and secondary causes in 9 children (39.1%). Seizure frequency improved for all 23 children (100%): Engel I was achieved in 15 children (65.2%), Engel II (26.1%) in six children, and Engel III (8.7%) in two children. Patients with seizure freedom had significantly fewer preoperative seizures per day than patients with seizure recurrence. Complications occurred in six children (26.1%): 2 wound infections, 2 meningitis, 1 femoral vein thrombosis, and 1 wound hematoma with return to OR. There were no perioperative mortality and no postoperative hydrocephalus or CSF diversion. QoL-related outcomes were available for 16 children: 16/16 (100%) reported that the surgery was a worthwhile and repeatable choice, 14 (87.5%) reported improved cognitive function, the median QOLCE-16 score was 62.5 ± 21. CONCLUSION/CONCLUSIONS:Hemispherotomy for DRE in selected children is a safe and effective surgery in a public children's hospital in a low-resource setting. At last follow-up, the majority of children were seizure-free, and all children had decreased seizure frequency. Families reported improved cognitive function, improved QoL and high satisfaction with their decision to pursue this surgery.
PMCID:13218697
PMID: 41037508
ISSN: 1423-0305
CID: 6039162
Neocortical tau burden determines the degree of cognitive impairment in individuals with Braak stage V neurofibrillary degeneration
Alzheimer disease neuropathologic change (ADNC) is considered to be the most common cause of cognitive decline and dementia worldwide. ADNC level is determined using the density of neuritic plaques in combination with the topographical distribution of β-amyloid (Aβ) plaques and hyperphosphorylated tau (p-tau)-positive neurofibrillary tangles (NFTs). While cognitive decline correlates with the level of ADNC, there remains a great deal of variation in cognitive outcomes between individuals that is unaccounted for by current neuropathologic evaluation metrics. We leveraged quantitative computer-assisted positive pixel assessments to establish the neocortical p-tau burden in the middle frontal and superior temporal gyri of 61 individuals with Braak NFT stage V who had a wide range of cognitive outcomes and trajectories. Frontal and temporal neocortical p-tau burden varied between 0.2% and 53.7%. Both frontal and temporal p-tau burden directly affected cognitive outcome and correlated with function of multiple cognitive domains, including measures of language/semantic memory and attention/working memory. In multivariable analysis, only p-tau burden and microinfarcts significantly impacted cognitive decline, while Aβ, limbic-predominant age-related TDP-43 encephalopathy, Lewy body pathology, and other measures of cerebrovascular disease did not. Additionally, individuals with low mean neocortical p-tau burden (≤ 13%) had significantly better longitudinal cognitive trajectories over the final 15 years of life compared to those with high burden (≥ 23.5%). These results suggest that while all individuals with Braak stage V have some degree of neurofibrillary degeneration in the neocortex, the significant variation in cognitive decline observed between these individuals can be partially understood as a reflection of the variation in quantitatively assessed neocortical p-tau burden, which had a greater impact on progression to dementia than common comorbid neuropathologies associated with dementia risk. This argues for the incorporation of the density of ADNC-related pathology, in addition to its regional location, as an adjunct to future staging systems for Alzheimer disease.
PMCID:13201366
PMID: 42184025
ISSN: 1432-0533
CID: 6039352
