Faculty Bibliography

BackgroundData-driven approaches identified Mild Motor Predominant (MMP), Intermediate (IM), and Diffuse Malignant (DM) as Parkinson's Disease (PD) subtypes with different motor and non-motor impairment at diagnosis. It remains unclear whether these subtypes remain stable over time or whether they represent distinct biological substrates. The alpha-synuclein seed amplification assay in CSF (CSF-αSyn-SAA) might provide further insights.Objectiveto evaluate the association between baseline CSF-αSyn-SAA parameters and 10-year clinical evolution of PD subtypes.Methods323 sporadic PD patients from PPMI dataset were classified as MMP, IM, or DM at baseline and 10-year follow-up based on motor, cognitive, sleep and dysautonomia features. CSF-αSyn-SAA parameters were collected at baseline using 150-h protocol. CSF Aβ1-42, tTau and pTau181, CSF and serum NfL were also considered at baseline.ResultsReaction times (T50, TTT) and area under the curve (AUC) respectively were shorter and larger in DM compared to IM/MMP. The difference in baseline amplification parameters was more evident when comparing subtypes based on 10-year clinical features (T50, η2 = 0.036; TTT, η2 = 0.031; AUC, η2 = 0.033; all p-values < 0.05) than when comparing subtypes based on baseline clinical features (T50, η2 = 0.012; TTT, η2 = 0.012; AUC, η2 = 0.013; all p < 0.05). Shorter T50 and TTT at baseline, or larger AUC, were associated with greater risk of DM versus MMP at 10-year follow-up (T50, OR = 4.1, p = 0.004; TTT, OR = 5.5, p < 0.001; AUC, OR = 3.5, p = 0.010). Aβ, Tau and NfL were similar between groups.ConclusionsBaseline CSF-αSyn-SAA parameters predicted long-term PD progression. Faster reactions were associated with a more severe 10-year PD phenotype considering motor and non-motor features.

Acute symptomatic seizures are a well recognized symptom of myelin oligodendrocyte antibody-associated disease (MOGAD), but long-term seizure outcomes and risk of epilepsy are understudied. In a retrospective cohort of 135 consecutive patients meeting consensus criteria for MOGAD without a prior diagnosis of epilepsy or concurrent NMDA-R Ab positivity, 19 developed seizures after MOGAD onset (16 %). Of these 19 patients, 7 patients (37 % of those with seizures, and 5 % of the total cohort). experienced one or more seizure recurrence during MOGAD remission (i.e. outside of an acute attack). Five of the 7 patients with recurrent seizures remained on antiseizure medication (ASM) (four on monotherapy and one on two ASMs) at last follow-up (median duration of follow up: 92 months). We discuss phenotypes of recurrent seizures in patients with MOGAD in the context of the conceptual framework of acute symptomatic seizures versus autoimmune encephalitis associated epilepsy (AEAE).

BACKGROUND:The cerebrospinal fluid alpha-synuclein seed amplification assay (CSFasynSAA) detects alpha-synuclein aggregation in over 90% of individuals with sporadic PD (sPD). However, the clinical characteristics of sPD with negative CSFasynSAA remain undefined. OBJECTIVES/OBJECTIVE:Describe clinical and neuroimaging characteristics of CSFasynSAA-negative sPD individuals in the Parkinson's Progression Markers Initiative (PPMI). METHODS:We identified sPD PPMI participants with a negative CSFasynSAA (SAA-, n = 80) or positive CSFasynSAA (SAA+, n = 856) result at baseline. For comparative analysis between groups, we used a reduced dataset (n = 79 SAA- and n = 237 SAA+) propensity-score matched on age, sex, and time since clinical diagnosis. Clinical parameters, dopamine transporter-single photon emission computed tomography (DAT-SPECT), and magnetic resonance imaging (MRI) brain volumetrics were analyzed. RESULTS:The SAA- and matched SAA+ groups had similar motor performance on the Movement Disorder Society Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III) and similar cognitive performance on the Montreal Cognitive Assessment (MoCA) at baseline. The proportion with severe hyposmia was 12% for SAA- versus 73% for SAA+ (P < 0.001). Per PPMI enrollment criteria all participants were classified as having an abnormal DAT-SPECT. There were no significant differences in median quantitative DAT-SPECT measures between groups. The SAA- group showed a higher degree of atrophy in subcortical brain regions including substantia nigra. Longitudinally, 14.3% of SAA- participants had a change in diagnosis versus 0.9% of SAA+ participants. CONCLUSIONS:At baseline, SAA- sPD PPMI participants have a substantially lower rate of hyposmia, but otherwise cannot be readily distinguished from SAA+ participants based on clinical characteristics. However, SAA- participants have a greater degree of subcortical brain atrophy, and approximately one out of seven SAA- participants received a change in diagnosis. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Antiseizure medications (ASMs) undergo marked pharmacokinetic alterations during pregnancy and postpartum. Suboptimal ASM management can lead to adverse maternal and child outcomes. However, there is scant literature to guide how to adjust ASM dosing. This study analyzed how ASMs were dosed in a large observational cohort study of pregnant women with epilepsy (PWWE) who had favorable seizure outcomes. METHODS:Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) was a prospective, observational cohort study that enrolled PWWE 2012-2016 across 20 US epilepsy centers. Inclusion criteria were PWWE, ages 14-45 years, and <20 weeks' gestational age. Seizures and ASM type(s) and doses were documented in a daily diary. Our analysis included ASM doses in pregnancy through early postpartum (6 weeks post-delivery). For each ASM, we analyzed percent participants who underwent ≥1 dose change in pregnancy and postpartum, time of first dose change after enrollment, time to subsequent changes, amount of each dose adjustment, and percent of conception dose at delivery and 6-week postpartum. RESULTS:A total of 299 participants (median 31 [range 17-46] years) were eligible for analysis. Median enrollment was 14-weeks gestation. Dose increases were made in 246/363 (67.8%) of ASMs during pregnancy beginning median 32 days post-enrollment; dose decreases were made within 6 weeks post-delivery for 171/357 (47.9%) of ASMs beginning median 3 days postpartum. For lamotrigine, 128/146 (87.7%) participants had doses increased, by 100 mg/d (median), reaching 191% of conception dose (mean) by delivery. Postpartum, 103/146 (70.5%) had dose tapers, by 100 mg/d (median), to 116% of conception dose (mean) by 6 weeks. For levetiracetam, 70/125 (56.0%) participants had doses increased, by 500 mg/d (median), reaching 177% of conception dose (mean) by delivery. Postpartum, 43/125 (34.4%) had dose tapers, by 500 mg/d (median), to 136% of conception dose (mean) by 6 weeks. For other ASMs, 10/14 had doses increased in pregnancy and 8/14 were tapered early postpartum. DISCUSSION/CONCLUSIONS:Previous MONEAD analyses showed no difference in seizure control between pregnant and nonpregnant women with epilepsy. We detail how ASMs were managed in pregnancy and early postpartum to achieve this favorable outcome. These findings can be useful for the management of PWWE. Limitations of this study include limited data in the first trimester, enrollment from epilepsy centers, and limited number of participants on a wider variety of ASMs. TRIAL REGISTRATION INFORMATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT01730170. Study Details | Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) | ClinicalTrials.gov. First submitted: November 9, 2012. First patient enrolled: December 19, 2012.

Prior expectation powerfully shapes perception, yet its effects have been notoriously difficult to characterize due to the confounding influence of attention. In this study, we systematically investigated expectation's influence on conscious visual object recognition while carefully disentangling it from attentional effects. Across three experiments, we observed that expectation's effect varied markedly depending on the experimental context. When expectation was manipulated in isolation, it enhanced recognition sensitivity, mirroring the effects of attention. However, when expectation and attention were orthogonally manipulated, a surprising interaction effect emerged whereby observers were less likely to report recognition of an expected stimulus in the unattended condition-an effect attributed to swap errors. Finally, a stronger expectation cue in both space and time reduced swap errors and increased the likelihood of observers reporting seeing the expected stimuli. These findings reveal a remarkable degree of flexibility and context dependence in expectation's influence on perception and shed new light on how attention and expectation jointly shape conscious object recognition.

BACKGROUND:Pain affects up to 87% of people with multiple system atrophy (MSA), but it remains unclear which types of pain contribute most to the overall burden. OBJECTIVE:To estimate the frequency of different types of pain in MSA individuals. METHODS:In 2023, individuals with MSA completed a web-based survey that included the King's Parkinson's Disease Pain Questionnaire (KPPQ) and additional questions addressing pain related to MSA core features (eg, coat-hanger pain, pain due to bladder-issues, cold extremities, bruises, and pressure sores). Respondents were matched by age, gender, and disease duration with historical cohorts of individuals with Parkinson's disease (PD) and healthy controls (n = 96 each) who had previously completed the KPPQ. RESULTS:One hundred and fifty-seven MSA individuals with pain completed the survey. The most frequently reported KPPQ types of pain were nocturnal pain (73%), musculoskeletal pain (63%), and fluctuation-related pain (62%). Common additional pain sources included coat-hanger pain (59%), cold extremities (48%), and bruises (44%). All KPPQ pain types were significantly more frequent in MSA than in healthy controls, except for musculoskeletal pain (63% vs. 66%, P = 0.722). Compared with PD, MSA individuals reported less musculoskeletal (63% vs. 78%, P = 0.023), but more orofacial pain (32% vs. 12%, P < 0.001) on the KPPQ. CONCLUSIONS:MSA is associated with both non-specific and disease-related pain types, which may be neuropathic, nociceptive, nociplastic, or mixed in nature. These findings inform the development of tailored tools for identifying distinct pain sources in MSA, as each may require a specific therapeutic approach, including targeted treatment of motor and non-motor symptoms. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

OBJECTIVE:The cause of perimesencephalic subarachnoid hemorrhage (pmSAH) is unclear but has historically been attributed to a venous source. The authors hypothesized that high-resolution cone-beam CT (CBCT) during angiography could better identify pmSAH etiology. METHODS:All patients with pmSAH treated at the authors' institution between January 2023 and December 2024 were retrospectively analyzed. Patients were excluded if CBCT was not performed as part of the digital subtraction angiography (DSA), if CBCT source data were not available for review, or if the images were deemed to be low quality. All images were reviewed by 2 neuroangiographers with extensive neurovascular imaging experience and discussed until consensus agreement. Data were recorded as counts and percentages. RESULTS:Among 152 patients who presented with spontaneous SAH in 2023-2024, 22 had a pmSAH defined according to the Rinkel criteria. These 22 patients had a catheter angiogram performed on 1 of 2 biplane machines. Thirteen of those patients had high-quality CBCT data available for review, 8 (61%) of whom were found to harbor a basilar perforator focal outpouching consistent with a site of rupture. All patients with pmSAH, including the 8 found to have a basilar perforator aneurysm, achieved an excellent neurological recovery with resolution of the basilar perforator finding on follow-up DSA with CBCT and without experiencing a re-rupture event or clinically significant vasospasm. CONCLUSIONS:In the setting of pmSAH, high-resolution CBCT acquired as part of catheter angiography frequently identifies a basilar perforator pseudoaneurysm. Conservative management was associated with excellent outcomes in this series. The authors propose that in the setting of pmSAH, a high suspicion of an arterial etiology should be considered until proven otherwise.

OBJECTIVES/OBJECTIVE:Cervical artery dissection (CeAD) is an important cause of ischemic stroke in young adults. Nearly 100 million annual chiropractic cervical manipulations are performed in the United States. The relationship between manipulation and CeAD remains controversial. METHODS:We analyzed patients in the multicenter STOP-CAD registry (n=4023) to identify CeAD cases diagnosed after chiropractic cervical manipulation. Demographics and clinical features were compared between manipulation-associated and nonmanipulation-associated cases using χ2 and t tests. Multivariable logistic regression identified key factors associated with manipulation-related CeAD. RESULTS:About 1 in 20 CeAD cases in this registry reported antecedent cervical manipulation. In multivariable binary logistic regression, compared with patients without prior manipulation, those with prior manipulation were younger (OR per year 0.98, 95% CI: 0.97-0.99, P=0.014), more often female (OR: 1.64, 95% CI: 1.21-2.23, P=0.001), less often diabetic (OR: 0.24, 95% CI: 0.08-0.78, P=0.018), presented with neck pain (OR: 2.80, 95% CI: 2.08-3.77, P<0.001), and had higher odds of isolated vertebral artery dissection (OR: 2.15, 95% CI: 1.57-2.94, P<0.001). Recurrent ischemic stroke rates were similar between groups. CONCLUSIONS:Given the very high number of manipulations performed annually, the absolute risk of secondary CeAD is extremely low. Manipulation-associated cases have distinct clinical features, occurring more often in younger women with vertebral dissections. Whether manipulation acts as a precipitating trigger or patients with early CeAD symptoms seek manipulation remains unresolved.