Therapeutic Advances in Neurological Disorders最新文献

Background: Low-grade epilepsy-associated brain tumors (LEATs) are found to be the second most common lesion-related epilepsy. Malignant potential of LEATs is very low and the overall survival is good, so the focus of treatment is focused more on seizure outcome rather than oncological prognosis.

Objectives: This study was conducted to evaluate the risk factors of seizure outcomes after resection in patients with LEATs.

Design: A retrospective study.

Methods: A retrospective analysis of patients with LEATs who underwent resective surgery in our three epilepsy centers between October 2010 and April 2023 with a minimum follow-up of 1 year. Demography, clinical characters, neurophysiology, and molecular neuropathology were assessed for association with postoperative seizure outcomes at 1-, 2-, and 5-year follow-up. Synthetic minority oversampling technique (SMOTE) algorithm model was performed to handle the imbalance of data distribution. Gaussian Naïve Bayes (GNB) algorithms were created as a basis for classifying outcomes according to observation indicators.

Results: A total of 111 patients were enrolled in the cohort. The most common pathology was ganglioglioma (n = 37, 33.3%). The percentage of patients with seizure freedom was 91.0% (101/111) at 1-year follow-up, 87.5% (77/88) at 2-year follow-up, and 79.1% (53/67) at 5-year follow-up. Partial resection had a significantly poor seizure outcome compared to total resection and supratotal resection (p < 0.05). The epileptiform discharge on post-resective intraoperative electrocorticography (ECoG) or postoperative scalp electroencephalography (EEG) were negative factors on postoperative seizure freedom at 1-, 2-, or 5-year follow-ups (p < 0.05). The area under the receiver-operating characteristic curve value of the GNB-SMOTE model was 0.95 (95% CI, 0.876-1.000), 0.892 (95% CI, 0.656-0.934), and 0.786 (95% CI, 0.491-0.937) at 1-, 2-, and 5-year follow-up, respectively.

Conclusion: The partial resection, post-resective intraoperative ECoG, and postoperative scalp EEG were valuable indicators of poor seizure outcomes. The utilization of post-resective intraoperative ECoG is beneficial to improve seizure outcomes. Based on the data diversity and completeness of three medical centers, a multivariate correlation analysis model was established based on GNB algorithm.

Acute disseminated encephalomyelitis and Guillain-Barré syndrome refer to post-infectious or post-vaccination inflammatory demyelinating disorders of central and peripheral nervous system, respectively. We report the case of a 60-year-old male patient presenting with irritability, gait difficulty, asymmetric quadriparesis (mostly in his left extremities), distal sensory loss for pain and temperature in left limbs, and reduced tendon reflexes in his upper limbs and absent in his lower limbs, following an upper respiratory tract infection, 3 weeks earlier. Brain magnetic resonance imaging revealed abnormal T2 signal and peripherally enhancing lesions in hemispheres, brainstem, and cerebellum. Nerve conduction studies were compatible with acute motor and sensory axonal neuropathy. Serology revealed positive IgM and IgG antibodies for Chlamydia pneumoniae, and he also tested positive for myelin oligodendrocyte glycoprotein (MOG) and sulfatide antibodies. Treatment with intravenous immunoglobulin and methylprednisolone led to clinical and radiological recovery within weeks. Even though several cases of combined central and peripheral demyelination have been reported before, it is the first case report with seropositive anti-sulfatide and anti-MOG acute sensorimotor axonal neuropathy and disseminated encephalitis associated with C. pneumoniae.

Background: Treatment guidelines recommend early disease-modifying therapy (DMT) initiation after diagnosis of multiple sclerosis (MS). Multinational comparative studies that assess time to DMT initiation in MS may allow detection of barriers inherent to healthcare systems to explain potential adverse systematic delays in commencing DMTs.

Objectives: To investigate and compare the time to first DMT and its association with sociodemographic and clinical variables after MS diagnosis in three large MS registries.

Design: This observational study was conducted using data from the German MS Registry (GMSR), the North American Research Committee on MS Registry (NARCOMS, US data only), and the United Kingdom MS Registry (UKMSR, both self- and clinician-reported).

Methods: Data from relapsing people with MS (PwMS), with a diagnosis of MS between 2014 and 2019, and available DMT and disability status were pooled using a meta-analytic approach.

Results: A total of 5395 PwMS were included in the analysis (GMSR: n = 2658; NARCOMS: n = 447; UKMSR: n = 2290). Kaplan-Meier estimates for the time to first DMT [median months (95% CI)] were 2.0 (1.9-2.0), 3.0 (2-4), and 9.0 (7.7-10.6) for GMSR, NARCOMS, and UKMSR, respectively. Pooled multivariable Cox regression demonstrated shorter time to first DMT for PwMS diagnosed after 2017 [1.65 (1.42-1.92), p < 0.01], and longer time to DMT when a higher-efficacy DMT was selected (0.69 (0.54-0.90), p < 0.0001].

Conclusion: Time to DMT initiation differs across the populations studied, indicating that barriers may exist in early access to DMT, particularly in the United Kingdom. However, a consistent decrease in time to DMT initiation was noted since 2017 across all registries. Further studies are warranted comparing the effects of time to DMT and time to higher-efficacy DMT on long-term outcome.

Background: More than half of patients with Parkinson's disease will experience psychosis symptoms in the form of hallucinations or delusions at some point over the course of their disease. These symptoms can significantly impact patients' health-related quality of life, cognitive abilities, and activities of daily living (ADLs) and function. Clinical assessment of how psychosis impacts these measures is crucial; however, few studies have assessed this sufficiently, in part due to a lack of appropriate scales for comprehensively assessing function.

Objective: The objective was to assess how symptoms of Parkinson's disease psychosis (PDP) impact ADLs and function, cognitive function, and health-related quality of life.

Design: To address this unmet need, we utilized a modified version of the Functional Status Questionnaire (mFSQ) to measure the impact of psychosis on ADLs and function in patients with PDP treated with pimavanserin, a US Food and Drug Administration-approved medication to treat hallucinations and delusions associated with PDP.

Methods: Eligible patients entered a 16-week, single-arm, open-label study of oral pimavanserin (34 mg) taken once daily. The primary endpoint was change from baseline to Week 16 on the mFSQ. Secondary endpoints included the Movement Disorders Society-modified Unified Parkinson's Disease Rating Scale (MDS-UPDRS) I and II; Schwab and England ADL; Clinical Global Impression-Severity of Illness (CGI-S), Clinical Global Impression-Improvement (CGI-I), and Patient Global Impression-Improvement (PGI-I), and were also measured as change from baseline to Week 16 using mixed-effects model for repeated measures (MMRM) and least-squares mean (LSM).

Results: Our results in a proof-of-concept, 16-week, open-label clinical study in 29 patients demonstrated that an improvement in psychosis symptoms following treatment with pimavanserin was associated with improvements in multiple measures of ADLs and function. Notably, a significant improvement was found on the primary endpoint, change from baseline to Week 16 in mFSQ score [LSM [SE] 14.0 [2.50], n = 17; 95% CI (8.8, 19.3); p < 0.0001].

Conclusion: These findings highlight the potential for improvement in function with improvement of psychosis symptoms in patients with PDP and suggest that the mFSQ may be a measurement tool to evaluate the level of improvement in function.

Trial registration: ClinicalTrials.gov Identifier: NCT04292223.

Introduction: Deep brain stimulation (DBS) is an established therapy for Parkinson's disease (PD) that can significantly improve motor symptoms and quality of life. Despite its effectiveness, little is known about patient perceptions of DBS.

Objectives: To evaluate patient perceptions of DBS for PD, focusing on understanding, satisfaction, and factors influencing their outlook. This study aims to enhance patient education and counseling by identifying key determinants of patient perceptions.

Design: A patient survey.

Methods: We surveyed 77 PD patients who had undergone DBS at multiple centers using a comprehensive questionnaire. The questionnaire included questions on demographic information, disease history, and detailed understanding about the indications for DBS, side effects, outlook, and other common misconceptions. We summarize data using measures of central tendency and dispersion appropriate to the data type (categorical, continuous, proportional) and model relationships among variables using fractional and linear regression methods.

Results: Participants had a median age of 66 years, were predominantly male (66%), Caucasian (90%), well-educated (79% with at least college degrees), and had a disease duration of greater than 5 years (97%). They conveyed good understanding of the signs and symptoms addressed by DBS across the motor and non-motor domains and associated side effects. Regression analysis identified age, disease duration, and education level as key determinants of patient understanding and outlook of DBS.

Conclusion: Our study provides a detailed understanding of patient perceptions of DBS for PD, including the benefits, challenges, and misconceptions. Our findings underscore the importance of identifying the causes of disparities in patient knowledge and perceptions regarding DBS to tailor patient counseling and ensure optimal treatment outcomes.

Background: Aggressive disease control soon after multiple sclerosis (MS) diagnosis may prevent irreversible neurological damage, and therefore early initiation of a high-efficacy disease-modifying therapy (DMT) is of clinical relevance.

Objectives: Evaluate long-term clinical outcomes in patients with MS who initiated treatment with either natalizumab or a BRACETD therapy (interferon beta, glatiramer acetate, teriflunomide, or dimethyl fumarate).

Design: This retrospective analysis utilized data from MSBase to create a matched population allowing comparison of first-line natalizumab to first-line BRACETD.

Methods: This study included patients who initiated treatment either with natalizumab or a BRACETD DMT within 1 year of MS diagnosis and continued treatment for ⩾6 months, after which patients could switch DMTs or discontinue treatment. Patients had a minimum follow-up time of ⩾60 months from initiation. A subgroup analysis compared the natalizumab group to patients in the BRACETD group who escalated therapy after 6 months. Outcomes included unadjusted annualized relapse rates (ARRs), time-to-first relapse, time-to-first confirmed disability improvement (CDI), and time-to-first confirmed disability worsening (CDW).

Results: After 1:1 propensity score matching, 355 BRACETD patients were matched to 355 natalizumab patients. Patients initiating natalizumab were less likely to experience a relapse over the duration of follow-up, with ARRs [95% confidence interval (CI)] of 0.080 (0.070-0.092) for natalizumab patients and 0.191 (0.178-0.205) for BRACETD patients (p < 0.0001). A Cox regression model of time-to-first relapse showed a reduced risk of relapse for natalizumab patients [hazard ratio (95% CI) of 0.52 (0.42-0.65); p < 0.001] and a more favorable time-to-first CDI. The risk of CDW was similar between groups. The subgroup analysis showed an increased relapse risk as well as a significantly higher risk of CDW for BRACETD patients.

Conclusion: Early initiation of natalizumab produced long-term benefits in relapse outcomes in comparison with BRACETD, regardless of a subsequent escalation in therapy.

We present a case of a 42-year-old woman with paraneoplastic anti-N-Methyl-D-Aspartat (NMDA)-receptor encephalitis and concurrent neuroborreliosis that was initially misdiagnosed as post-COVID-19 syndrome. Clinically, the patient presented with a range of chronic and subacute neuropsychiatric symptoms and recalled a tick bite weeks prior to admission. The patient had undergone psychiatric and complementary medical treatments for 1 year before admission and was initially diagnosed with post-COVID-19 syndrome. Admission was performed because of acute worsening with fever, confusion, and unsteady gait. Cerebrospinal fluid (CSF) analysis revealed pleocytosis with elevated borrelia Immunoglobulin M (IgM) and Immunoglobulin M (IgG) CSF/blood antibody indices, indicating acute neuroborreliosis. Anti-NMDA receptor antibodies were identified in the CSF via a cell-based assay and were confirmed by an external laboratory. Other paraneoplastic antibodies were ruled out during in-house examination. Cranial Magnetic resonance imaging (MRI) revealed basal meningitis, rhomb- and limbic encephalitis. A subsequent pelvic Computer tomography (CT) scan identified an ovarian teratoma. The patient's clinical condition improved dramatically with antibiotic treatment and plasmapheresis, the teratoma was surgically removed and she was started on rituximab. Our case highlights that amidst the prevailing focus on COVID-19-related health concerns, other well-established, but rare neurological conditions should not be neglected. Furthermore, our case illustrates that patients may suffer from multiple, concurrent, yet pathophysiologically unrelated neuroinflammatory conditions.

Background: Cerebral pulsatility is thought to reflect arterial stiffness and downstream microvascular resistance. Although previous studies indicated cerebral pulsatility might closely relate to development of cerebral small vessel disease (SVD), yet evidence remain controversial and longitudinal data are rare.

Objective: We aimed to explore relationships of cerebral pulsatility with severity and progression of various SVD imaging markers among the community-dwelling elderly.

Design: A longitudinal cohort study.

Methods: As part of the prospective community-based Shanghai Aging Study cohort, dementia- and stroke-free elderly were recruited for baseline assessment of cerebral pulsatility and SVD severity during 2010-2011 and traced for SVD progression during 2016-2017. Cerebral pulsatility was quantified for both anterior and posterior circulation with transcranial Doppler ultrasound. SVD imaging markers were measured with brain magnetic resonance imaging (MRI) including white matter hyperintensities (WMHs), enlarged perivascular spaces (ePVS), lacunes, and microbleeds. The cross-sectional and longitudinal relationships between cerebral pulsatility and SVD were analyzed by univariable and multivariable regression models.

Results: Totally, 188 eligible subjects were included at baseline and out of them, 100 (53.19%) returned for a 7-year follow-up. At baseline, increased pulsatility of posterior circulation was independently associated with more periventricular WMH (PWMH) and ePVS in basal ganglia (BG-ePVS) but not with other SVD markers. Longitudinally, higher posterior pulsatility predicted greater PWMH progression in participants with hypertension (β = 2.694, standard error [SE] = 1.112, p = 0.020), whereas pulsatility of anterior circulation was shown to prevent BG-ePVS progression among followed-up elderly (β = -6.737, SE = 2.685, p = 0.012). However, no significant relationship was found between cerebral pulsatility and burden of lacunes or cerebral microbleeds.

Conclusion: Higher pulsatility of posterior circulation could worsen PWMH progression, especially for participants with hypertension. But for development of ePVS, increased cerebral pulsatility could play a compensatory role among several healthy elderly. The distinct relationships between cerebral pulsatility and various SVD markers emphasized the importance of individualized SVD management.

Background: Pregnancy in patients with multiple sclerosis (MS) is accompanied by a decline of relapse activity with increased risk of relapses 3 months post-partum, for unknown reasons. Eomesodermin⁺ T-helper cells (Eomes⁺ Th cells) are known to mediate neuroinflammation and disease progression in MS and are induced by prolactin-secreting cells.

Objectives: Here, investigated immune cell alterations and the pathophysiological role of Eomes⁺ Th cells for disease activity during pregnancy and post-partum in MS.

Methods: We enrolled n = 81 pregnant patients with relapsing-remitting MS (RRMS), n = 27 post-partum RRMS and n = 26 female RRMS control patients under the umbrella of the German Multiple Sclerosis and Pregnancy Registry. Clinical data were collected and immune cell alterations were analysed using flow cytometry.

Results: While CD3⁺CD4⁺ Th cells were unaffected, CD3⁺CD8⁺ cytotoxic T-cells were elevated post-partum (p = 0.02) with reduced B-cell frequencies (p = 0.01) compared to non-pregnant RRMS patients. NK cells were elevated during first trimester (p = 0.02) compared to the third trimester. Frequencies of Eomes⁺ Th and Eomes⁺ Tc cells did not differ. There was no correlation of prolactin release and expression of Eomes⁺ Th cells. However, Eomes⁺ Th cells correlated with lower frequencies of regulatory T-cells during second (r = -0.42; p < 0.05) and third trimester (r = -0.37; p < 0.05). Moreover, Eomes⁺ Th cells correlated with frequencies of B-cells during third trimester (r = 0.54; p = 0.02). Frequencies of Eomes⁺ Th cells were not associated with the number of relapses before pregnancy, during pregnancy or post-partum. However, Eomes⁺ Th cells strongly correlated with disability post-partum as assessed using the EDSS (r = 0.52; p = 0.009).

Discussion: Pregnancy in MS is associated with robust immunological alterations. Eomes⁺ Th cells are capable of inducing immune cell alterations during the course of pregnancy, most evident during the second and third trimester as shown with a correlation of reduced Treg cells and a significant increase of B-cells. Importantly, Eomes⁺ Th cells correlate with disability post-partum. In summary, during late pregnancy in MS an inflammatory, cytotoxic and dysregulated immunological environment is primed gaining function post-delivery. This may be responsible for post-partum disability accumulation.

Background: Post-acute sequelae of COVID-19 (PASC) comprise a broad spectrum of symptoms such as fatigue, general weakness, compromised attention and sleep or anxiety disorders. PASC represents a medical and socio-economic challenge.

Objectives: Our study evaluated cytokines (IL-1β, IL-6 and TNFα) and cortisol levels in a cohort of typical patients with PASC, suffering concentration problems, fatigue and difficulties finding words.

Design: This was a prospective cohort study. Four groups were analysed and compared: those who had never contracted SARS-CoV-2 (n = 13), infected but had no PASC (n = 34), infected with former PASC that resolved (n = 40) and patients with ongoing PASC after infection (n = 91).

Methods: Cytokine and cortisol serum levels were determined in patients' blood samples.

Results: Cytokine levels of IL-1β, IL-6, TNFα and cortisol levels did not differ between groups analysed.

Conclusion: This may indicate a non-organic/psychosomatic genesis of PASC; further studies are needed to elucidate the underlying causes of PACS, and non-organic causes should not be overlooked.