Longitudinal Free-Water Changes in Dementia with Lewy Bodies.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (dMRI) examines tissue microstructure integrity in vivo. Prior dementia with Lewy bodies (DLB) diffusion tensor imaging studies yielded mixed results. OBJECTIVE: We employed free-water (FW) imaging to assess DLB progression and correlate with clinical decline in DLB. METHODS: Baseline and follow-up MRIs were obtained at 12 and/or 24 months for 27 individuals with DLB or mild cognitive impairment with Lewy bodies (MCI-LB). FW was analyzed using the Mayo Clinic Adult Lifespan Template. Primary outcomes were FW differences between baseline and 12 or 24 months. To compare FW change longitudinally, we included 20 cognitively unimpaired individuals from the Alzheimer's Disease Neuroimaging Initiative. RESULTS: We followed 23 participants to 12 months and 16 participants to 24 months. Both groups had worsening in Montreal Cognitive Assessment (MoCA) and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores. We found significant FW increases at both time points compared to baseline in the insula, amygdala, posterior cingulum, parahippocampal, entorhinal, supramarginal, fusiform, retrosplenial, and Rolandic operculum regions. At 24 months, we found more widespread microstructural changes in regions implicated in visuospatial processing, motor, and cholinergic functions. Between-group analyses (DLB vs. controls) confirmed significant FW changes over 24 months in most of these regions. FW changes were associated with longitudinal worsening of MDS-UPDRS and MoCA scores. CONCLUSIONS: FW increased in gray and white matter regions in DLB, likely due to neurodegenerative pathology associated with disease progression. FW change was associated with clinical decline. The findings support dMRI as a promising tool to track disease progression in DLB. © 2024 International Parkinson and Movement Disorder Society.

Modulation of immune cell reactivity with cis-binding Siglec agonists.

Inflammatory pathologies caused by phagocytes lead to numerous debilitating conditions, including chronic pain and blindness due to age-related macular degeneration. Many members of the sialic acid-binding immunoglobulin-like lectin (Siglec) family are immunoinhibitory receptors whose agonism is an attractive approach for antiinflammatory therapy. Here, we show that synthetic lipid-conjugated glycopolypeptides can insert into cell membranes and engage Siglec receptors in cis, leading to inhibitory signaling. Specifically, we construct a cis-binding agonist of Siglec-9 and show that it modulates mitogen-activated protein kinase (MAPK) signaling in reporter cell lines, immortalized macrophage and microglial cell lines, and primary human macrophages. Thus, these cis-binding agonists of Siglecs present a method for therapeutic suppression of immune cell reactivity.

Differentiating Prodromal Dementia with Lewy Bodies from Prodromal Alzheimer's Disease: A Pragmatic Review for Clinicians.

This pragmatic review synthesises the current understanding of prodromal dementia with Lewy bodies (pDLB) and prodromal Alzheimer's disease (pAD), including clinical presentations, neuropsychological profiles, neuropsychiatric symptoms, biomarkers, and indications for disease management. The core clinical features of dementia with Lewy bodies (DLB)-parkinsonism, complex visual hallucinations, cognitive fluctuations, and REM sleep behaviour disorder are common prodromal symptoms. Supportive clinical features of pDLB include severe neuroleptic sensitivity, as well as autonomic and neuropsychiatric symptoms. The neuropsychological profile in mild cognitive impairment attributable to Lewy body pathology (MCI-LB) tends to include impairment in visuospatial skills and executive functioning, distinguishing it from MCI due to AD, which typically presents with impairment in memory. pDLB may present with cognitive impairment, psychiatric symptoms, and/or recurrent episodes of delirium, indicating that it is not necessarily synonymous with MCI-LB. Imaging, fluid and other biomarkers may play a crucial role in differentiating pDLB from pAD. The current MCI-LB criteria recognise low dopamine transporter uptake using positron emission tomography or single photon emission computed tomography (SPECT), loss of REM atonia on polysomnography, and sympathetic cardiac denervation using meta-iodobenzylguanidine SPECT as indicative biomarkers with slowing of dominant frequency on EEG among others as supportive biomarkers. This review also highlights the emergence of fluid and skin-based biomarkers. There is little research evidence for the treatment of pDLB, but pharmacological and non-pharmacological treatments for DLB may be discussed with patients. Non-pharmacological interventions such as diet, exercise, and cognitive stimulation may provide benefit, while evaluation and management of contributing factors like medications and sleep disturbances are vital. There is a need to expand research across diverse patient populations to address existing disparities in clinical trial participation. In conclusion, an early and accurate diagnosis of pDLB or pAD presents an opportunity for tailored interventions, improved healthcare outcomes, and enhanced quality of life for patients and care partners.

Objects and categories: feature statistics and object processing in the ventral stream.

Recognizing an object involves more than just visual analyses; its meaning must also be decoded. Extensive research has shown that processing the visual properties of objects relies on a hierarchically organized stream in ventral occipitotemporal cortex, with increasingly more complex visual features being coded from posterior to anterior sites culminating in the perirhinal cortex (PRC) in the anteromedial temporal lobe (aMTL). The neurobiological principles of the conceptual analysis of objects remain more controversial. Much research has focused on two neural regions-the fusiform gyrus and aMTL, both of which show semantic category differences, but of different types. fMRI studies show category differentiation in the fusiform gyrus, based on clusters of semantically similar objects, whereas category-specific deficits, specifically for living things, are associated with damage to the aMTL. These category-specific deficits for living things have been attributed to problems in differentiating between highly similar objects, a process that involves the PRC. To determine whether the PRC and the fusiform gyri contribute to different aspects of an object's meaning, with differentiation between confusable objects in the PRC and categorization based on object similarity in the fusiform, we carried out an fMRI study of object processing based on a feature-based model that characterizes the degree of semantic similarity and difference between objects and object categories. Participants saw 388 objects for which feature statistic information was available and named the objects at the basic level while undergoing fMRI scanning. After controlling for the effects of visual information, we found that feature statistics that capture similarity between objects formed category clusters in fusiform gyri, such that objects with many shared features (typical of living things) were associated with activity in the lateral fusiform gyri whereas objects with fewer shared features (typical of nonliving things) were associated with activity in the medial fusiform gyri. Significantly, a feature statistic reflecting differentiation between highly similar objects, enabling object-specific representations, was associated with bilateral PRC activity. These results confirm that the statistical characteristics of conceptual object features are coded in the ventral stream, supporting a conceptual feature-based hierarchy, and integrating disparate findings of category responses in fusiform gyri and category deficits in aMTL into a unifying neurocognitive framework.

Sex differences in dementia with Lewy bodies: Focused review of available evidence and future directions.

In this review, we summarize the current knowledge on sex differences in dementia with Lewy bodies (DLB) relating to epidemiology, clinical features, neuropathology, biomarkers, disease progression, and caregiving. While many studies show a higher DLB prevalence in men, this finding is inconsistent and varies by study approach. Visual hallucinations may be more common and occur earlier in women with DLB, whereas REM sleep behavior disorder may be more common and occur earlier in men. Several studies report a higher frequency of parkinsonism in men with DLB, while the frequency of fluctuations appears similar between sexes. Women tend to be older, have greater cognitive impairment at their initial visit, and are delayed in meeting DLB criteria compared to men. Women are also more likely to have Lewy body disease with co-existing AD-related pathology than so-called "pure" Lewy body disease, while men may present with either. Research is mixed regarding the impact of sex on DLB progression. Biomarker and treatment research assessing for sex differences is lacking. Women provide the majority of caregiving in DLB but how this affects the caregiving experience is uncertain. Gaining a better understanding of sex differences will be instrumental in aiding future development of sex-specific strategies in DLB for early diagnosis, care, and drug development.

Interactive mobile application for Parkinson's disease deep brain stimulation (MAP DBS): An open-label, multicenter, randomized, controlled clinical trial.

INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), but its efficacy is tied to DBS programming, which is often time consuming and burdensome for patients, caregivers, and clinicians. Our aim is to test whether the Mobile Application for PD DBS (MAP DBS), a clinical decision support system, can improve programming. METHODS: We conducted an open-label, 1:1 randomized, controlled, multicenter clinical trial comparing six months of SOC standard of care (SOC) to six months of MAP DBS-aided programming. We enrolled patients between 30 and 80 years old who received DBS to treat idiopathic PD at six expert centers across the United States. The primary outcome was time spent DBS programming and secondary outcomes measured changes in motor symptoms, caregiver strain and medication requirements. RESULTS: We found a significant reduction in initial visit time (SOC: 43.8 ± 28.9 min n = 37, MAP DBS: 27.4 ± 13.0 min n = 35, p = 0.001). We did not find a significant difference in total programming time between the groups over the 6-month study duration. MAP DBS-aided patients experienced a significantly larger reduction in UPDRS III on-medication scores (-7.0 ± 7.9) compared to SOC (-2.7 ± 6.9, p = 0.01) at six months. CONCLUSION: MAP DBS was well tolerated and improves key aspects of DBS programming time and clinical efficacy.

Lewy Body Dementias: Controversies and Drug Development.

Lewy body dementia (LBD) is one of the most common neurodegenerative dementias. Clinical trials for symptomatic and disease-modifying therapies in LBD remain a national research priority, but there are many challenges in both past and active drug developments in LBD. This review highlights the controversies in picking the appropriate populations, interventions, target selections, and outcome measures, which are all critical components of clinical trial implementation in LBD. The heterogeneity of LBD neuropathology and clinical presentations, limited understanding of core features such as cognitive fluctuations, and lack of validated LBD-specific outcome measures and biomarkers represent some of the major challenges in LBD trials.

Kinder Ready Clinics: A Collaborative Model for Creating Equitable and Engaged Early Learning Environments for Low-income Families.

Disparities in children's school readiness (SR) in the U.S. are well-documented and have detrimental long-term consequences. Clinic-based early education interventions are limited. This report summarizes collaborative efforts of pediatricians and community stakeholders to develop and implement clinic-based interventions to promote early learning and SR among low-income children.

Rhabdomyolysis secondary to severe tic fits.

Tourette syndrome (TS) is a condition wherein motor and vocal tics occur, provoked by an urge, but often not able to be completely voluntarily controlled. Tics are known to cause physical and emotional risks to quality of life, and in rare extreme cases, may have permanent consequences. We report the first cases, to our knowledge, of rhabdomyolysis due to extreme tic fits in two distinct patients with TS. Both patients presented with severe tics, leading to elevated creatine kinase and a diagnosis of rhabdomyolysis requiring hospitalisation and intravenous fluids. Neither had neuroleptic malignant syndrome. One patient was on concurrent neuroleptic therapy, but his laboratory parameters improved when tics subsided despite continued neuroleptic use. Our cases highlight the potential complication of rhabdomyolysis secondary to severe tic fits independent of neuroleptic use.

An Update on Botulinum Toxin in Neurology.

Botulinum neurotoxin (BoNT) is an effective treatment for many neurologic disorders. This article gives a comprehensive overview of the clinical applications of BoNT across the field of neurology.

Emerging Neuroimaging Biomarkers Across Disease Stage in Parkinson Disease: A Review.

Importance: Imaging biomarkers in Parkinson disease (PD) are increasingly important for monitoring progression in clinical trials and also have the potential to improve clinical care and management. This Review addresses a critical need to make clear the temporal relevance for diagnostic and progression imaging biomarkers to be used by clinicians and researchers over the clinical course of PD. Magnetic resonance imaging (diffusion imaging, neuromelanin-sensitive imaging, iron-sensitive imaging, T1-weighted imaging), positron emission tomography/single-photon emission computed tomography dopaminergic, serotonergic, and cholinergic imaging as well as metabolic and cerebral blood flow network neuroimaging biomarkers in the preclinical, prodromal, early, and moderate to late stages are characterized. Observations: If a clinical trial is being carried out in the preclinical and prodromal stages, potentially useful disease-state biomarkers include dopaminergic imaging of the striatum; metabolic imaging; free-water, neuromelanin-sensitive, and iron-sensitive imaging in the substantia nigra; and T1-weighted structural magnetic resonance imaging. Disease-state biomarkers that can distinguish atypical parkinsonisms are metabolic imaging, free-water imaging, and T1-weighted imaging; dopaminergic imaging and other molecular imaging track progression in prodromal patients, whereas other established progression biomarkers need to be evaluated in prodromal cohorts. Progression in early-stage PD can be monitored using dopaminergic imaging in the striatum, metabolic imaging, and free-water and neuromelanin-sensitive imaging in the posterior substantia nigra. Progression in patients with moderate to late-stage PD can be monitored using free-water imaging in the anterior substantia nigra, R2* of substantia nigra, and metabolic imaging. Cortical thickness and gyrification might also be useful markers or predictors of progression. Dopaminergic imaging and free-water imaging detect progression over 1 year, whereas other modalities detect progression over 18 months or longer. The reliability of progression biomarkers varies with disease stage, whereas disease-state biomarkers are relatively consistent in individuals with preclinical, prodromal, early, and moderate to late-stage PD. Conclusions and Relevance: Imaging biomarkers for various stages of PD are readily available to be used as outcome measures in clinical trials and are potentially useful in multimodal combination with routine clinical assessment. This Review provides a critically important template for considering disease stage when implementing diagnostic and progression biomarkers in both clinical trials and clinical care settings.

Advances and Future Directions of Neuromodulation in Neurologic Disorders.

"Deep brain stimulation is a safe and effective therapy for the management of a variety of neurologic conditions with Food and Drug Administration or humanitarian exception approval for Parkinson disease, dystonia, tremor, and obsessive-compulsive disorder. Advances in neurophysiology, neuroimaging, and technology have driven increasing interest in the potential benefits of neurostimulation in other neuropsychiatric conditions including dementia, depression, pain, Tourette syndrome, and epilepsy, among others. New anatomic or combined targets are being investigated in these conditions to improve symptoms refractory to medications or standard stimulation."

Deep brain stimulation programming strategies: segmented leads, independent current sources, and future technology.

Introduction: Advances in neuromodulation and deep brain stimulation (DBS) technologies have facilitated opportunities for improved clinical benefit and side effect management. However, new technologies have added complexity to clinic-based DBS programming.Areas covered: In this article, we review basic basal ganglia physiology, proposed mechanisms of action and technical aspects of DBS. We discuss novel DBS technologies for movement disorders including the role of advanced imaging software, lead design, IPG design, novel programming techniques including directional stimulation and coordinated reset neuromodulation. Additional topics include the use of potential biomarkers, such as local field potentials, electrocorticography, and adaptive stimulation. We will also discuss future directions including optogenetically inspired DBS.Expert opinion: The introduction of DBS for the management of movement disorders has expanded treatment options. In parallel with our improved understanding of brain physiology and neuroanatomy, new technologies have emerged to address challenges associated with neuromodulation, including variable effectiveness, side-effects, and programming complexity. Advanced functional neuroanatomy, improved imaging, real-time neurophysiology, improved electrode designs, and novel programming techniques have collectively been driving improvements in DBS outcomes.

Mediterranean Diet Adherence in People With Parkinson's Disease Reduces Constipation Symptoms and Changes Fecal Microbiota After a 5-Week Single-Arm Pilot Study.

Introduction: Non-motor symptoms of Parkinson's disease (PD) such as gastrointestinal (GI) dysfunction are common, yet little is known about how modifying dietary intake impacts PD symptoms. The aim of this study in individuals with PD was to determine whether a Mediterranean diet intervention is feasible and affects GI function, intestinal permeability and fecal microbial communities. Methods: A single-arm, 5-week Mediterranean diet intervention study was conducted in eight people with PD. Daily and weekly questionnaires were administered to determine changes in GI symptoms. Urine and stool samples were collected at baseline and after 5 weeks to assess intestinal permeability and fecal microbial communities. Additionally, live-in partners of the participants with PD were matched as controls (n = 8) for baseline urine and stool samples. Results: Participants with PD increased intake of Mediterranean diet based on adherence scores from baseline to week 5 (4.4 ± 0.6 vs. 11.9 ± 0.7; P < 0.01 with >10 representing good adherence), which was linked with weight loss (77.4 kg vs. 74.9 kg, P = 0.01). Constipation syndrome scores decreased after 5 weeks (2.3 ± 0.5 vs. 1.5 ± 0.3; P = 0.04). Bilophila, was higher at baseline in PD (0.6 ± 0.1% vs. 0.2 ± 0.1% P = 0.02) and slightly decreased after the diet intervention (0.5 ± 0.1%; P = 0.01). Interestingly, the proportion of Roseburia was significantly lower in PD compared to controls (0.6 ± 0.2% vs. 1.6 ± 0.3%; P = 0.02) and increased at week 5 (0.9 ± 0.2%; P < 0.01). No differences were observed for markers of intestinal permeability between the control and PD groups or post-intervention. Conclusions: Short-term Mediterranean diet adherence is feasible in participants with PD; correlated with weight loss, improved constipation, and modified gut microbiota. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03851861.

Home Health Management of Parkinson Disease Deep Brain Stimulation: A Randomized Clinical Trial.

Importance: The travel required to receive deep brain stimulation (DBS) programming causes substantial burden on patients and limits who can access DBS therapy. Objective: To evaluate the efficacy of home health DBS postoperative management in an effort to reduce travel burden and improve access. Design, Settings, and Participants: This open-label randomized clinical trial was conducted at University of Florida Health from November 2017 to April 2020. Eligible participants had a diagnosis of Parkinson disease (PD) and were scheduled to receive DBS independently of the study. Consenting participants were randomized 1:1 to receive either standard of care or home health postoperative DBS management for 6 months after surgery. Primary caregivers, usually spouses, were also enrolled to assess caregiver strain. Interventions: The home health postoperative management was conducted by a home health nurse who chose DBS settings with the aid of the iPad-based Mobile Application for PD DBS system. Prior to the study, the home health nurse had no experience providing DBS care. Main Outcomes and Measures: The primary outcome was the number of times each patient traveled to the movement disorders clinic during the study period. Secondary outcomes included changes from baseline on the Unified Parkinson's Disease Rating Scale part III. Results: Approximately 75 patients per year were scheduled for DBS. Of the patients who met inclusion criteria over the entire study duration, 45 either declined or were excluded for various reasons. Of the 44 patients enrolled, 19 of 21 randomized patients receiving the standard of care (mean [SD] age, 64.1 [10.0] years; 11 men) and 23 of 23 randomized patients receiving home health who underwent a minimum of 1 postoperative management visit (mean [SD] age, 65.0 [10.9] years; 13 men) were included in analysis. The primary outcome revealed that patients randomized to home health had significantly fewer clinic visits than the patients in the standard of care arm (mean [SD], 0.4 [0.8] visits vs 4.8 [0.4] visits; P < .001). We found no significant differences between the groups in the secondary outcomes measuring the efficacy of DBS. No adverse events occurred in association with the study procedure or devices. Conclusions and Relevance: This study provides evidence supporting the safety and feasibility of postoperative home health DBS management. Trial Registration: ClinicalTrials.gov Identifier: NCT02474459.

MR characteristics of unruptured intracranial arteriovenous malformations associated with seizure as initial clinical presentation.

BACKGROUND: Patients with intracranial arteriovenous malformations (AVMs) are at increased risk of seizures. OBJECTIVE: To identify MRI characteristics of unruptured intracranial AVMs associated with seizures at presentation. MATERIALS AND METHODS: A retrospective review was completed of patients diagnosed with unruptured intracranial AVMs on MRI between January 1, 2000 and December 31, 2016. Two blinded reviewers assessed demographics, lesion locality, and imaging and architectural characteristics of AVMs and surrounding parenchyma, including, but not limited to, AVM location, venous drainage pattern, venous varix, thrombosed venous varix, long draining vein, AVM-related gliosis, peri-AVM edema, and peri-AVM T2* signal. Findings were statistically analyzed for correlation with seizure using Student's t-test for continuous variables and Χ2 test for categorical variables. RESULTS: Of 165 included patients, 57/165 (34.5%) patients were imaged as part of an investigation for seizures. Patients with seizures more commonly had peri-AVM edema (36.8%, compared with 11.1% of non-seizure patients, p<0.0001), peri-AVM T2* blooming (28.1% vs 7.4%; p=0.029), a venous pouch/varix (61.4% vs 31.5%, p=0.0003), long draining vein (91.2% vs 55.6%, p<0.0001), and larger size based on Spetzler-Martin grade categorization (p=0.006). By location, AVMs located in the frontal lobe, primary motor cortex, and primary sensory cortex were associated with seizures (p=0.004, p=0.001, and p=0.006, respectively); temporal lobe location was not associated with seizures (p=0.459). CONCLUSIONS: Certain MRI characteristics of unruptured intracranial AVMs are associated with seizures. Such correlations may assist in identifying the pathophysiological mechanisms by which AVMs cause seizures.

High-dose Botulinum Toxin Therapy: Safety, Benefit, and Endurance of Efficacy.

Background: Botulinum neurotoxin therapy (BoNT) is a powerful tool for treating many neurologic disorders. The U.S. Food and Drug Administration (FDA)-approved maximum onabotulinum toxin A (OnaA) dose is 400 units (U) per visit, but higher doses are commonly necessary, particularly when treating multiple body regions. Methods: We collected demographics, OnaA dose, body regions injected and indications, patient-reported efficacy via 7-point Clinical Global Impression Scale (CGIS), and duration of benefit. Results: Sixty-eight patients were identified receiving OnaA >400 U/session. Dystonia (n = 44) and spasticity (n = 24) were the most common indications for high-dose OnaA. Mean duration of benefit was 9 weeks (standard deviation [SD] 3). More than 70% of patients self-reported "very much improved" or "much improved" at 6 month, 1 year, and last visit. No serious adverse effects were reported. Discussion: The majority of patients tolerated >400 U OnaA with continued benefit. OnaA doses >400 U may be safe and effective in appropriate patients.

Ataxia and tolerance after thalamic deep brain stimulation for essential tremor.

BACKGROUND: Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) thalamus is highly effective to treat medication-refractory essential tremor (ET). Complications of stimulation-induced ataxia and tolerance have been reported in limited series, ranging from 5 to 40%. OBJECTIVE: We analyzed a large single-center cohort of ET patients treated with thalamic DBS to assess rates of ataxia and tolerance. METHODS: Retrospective study of all ET patients that underwent VIM DBS at Mayo Clinic from 2010 to 2014. Demographic, clinical and DBS data were extracted. Risk factors, complications and time to onset of tolerance and ataxia were examined. RESULTS: One hundred and thirteen ET patients (51% male) of mean age 68 ± 10 years and mean ET duration 27 ± 18 years underwent DBS during the study period. Of these, 98 (87%) had follow-up of ≥6 months (mean 4.0 ± 1.5 years) and were included for analysis. Complications of isolated ataxia (26%), isolated tolerance (4%), both tolerance and ataxia (9%), or neither (61%) were identified. Development of ataxia was about 3 times more common than tolerance (35% vs. 13%). The mean time to ataxia was 5.5 ± 0.3 years postoperatively. Risk factors for ataxia were baseline ataxic features, older age, and shorter ET disease duration. Small sample size limited calculation of risk factors and onset time for tolerance. CONCLUSIONS: Stimulation-related ataxia occurred in one-third of ET patients, while tolerance was less common. Presence of baseline ataxia, age, and disease duration may aid counseling of stimulation-related ataxia risk. Larger studies are warranted to confirm these findings and further assess risk factors for tolerance.

Deep brain stimulation and other surgical modalities for the management of essential tremor.

INTRODUCTION: Surgical treatments are considered for essential tremor (ET) when patients do not respond to oral pharmacological therapies. These treatments mainly comprise radiofrequency (RF) thalamotomy, gamma knife radiosurgery (GKRS), deep brain stimulation (DBS), and focused ultrasound (FUS) procedures. AREAS COVERED: We reviewed the strengths and weaknesses of each procedure and clinical outcomes for 7 RF studies (n = 85), 11 GKRS (n = 477), 33 DBS (n = 1061), and 13 FUS studies (n = 368). A formal comparison was not possible given the heterogeneity in studies. Improvements were about 42%-90% RF, 10%-79% GKRS, 45%-83% DBS, 42%-83% FUS at short-term follow-up (<12 months) and were about 54%-82% RF, 11%-84% GKRS, 18%-92% DBS, and 42%-80% FUS at long-term follow-up (>12 months). EXPERT OPINION: We found DBS with inherent advantages of being an adjustable and reversible procedure as the most frequently employed surgical procedure for control of ET symptoms. FUS is a promising procedure but has limited applicability for unilateral control of symptoms. RF is invasive, and GKRS has unpredictable delayed effects. Each of these surgical modalities has advantages and limitations that need consideration when selecting a treatment for the ET patients.

Changes in Clinical Presentation and Treatment Over Time in Patients with Unruptured Intracranial Arteriovenous Malformations.

OBJECTIVE: Treatment of unruptured intracranial arteriovenous malformations (AVMs) has become controversial since the ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) study was published in 2014. We sought to analyze changes in the demographics, clinical presentation, and treatment strategies in 2 patient cohorts from the same institution separated by 40 years. METHODS: We retrospectively reviewed the electronic medical records for a consecutive series of patients with unruptured intracranial AVMs seen at the Mayo Clinic between 2003 and 2017 and compared them with a previously published historical cohort from the same institution seen between 1974 and 1985. RESULTS: There were 273 patients in the contemporary cohort, of which discovery of the AVM was incidental in 123 (45.1%), a 3.5-fold increase compared with the 13.1% out of 168 patients in the historical cohort (P < 0.0001). Consequently, the percentage of patients with seizures as the presenting symptom leading to the diagnosis of AVM decreased from 57.7% in the historical cohort to 28.9% in the contemporary cohort (P < 0.0001). Interventional treatment was utilized in 220 (81.5%) contemporary patients compared with 49 (29.2%) historical patients (P < 0.0001). CONCLUSIONS: Compared to 40 years ago, more patients are presenting with incidentally discovered intracranial AVMs and are undergoing interventional treatment. Better understanding of the natural history, developments in endovascular therapy, and stereotactic radiosurgery, as well as improvements in microsurgical techniques have led to a substantial increase in patients undergoing invasive treatment.