INTRODUCTION:Carotid-cavernous fistulas (CCFs) are abnormal shunts between the internal carotid artery and the cavernous sinus that may be high-flow direct or low-flow indirect lesions. They present with ocular symptoms and headache and are diagnosed primarily by cerebral angiography. This study evaluated the safety, technical success, and long-term outcomes of endovascular embolization for CCFs. MATERIAL AND METHODS:This retrospective single-center study evaluated procedural and clinical outcomes of patients with CCFs treated with endovascular embolization. The evaluated outcomes included immediate procedural success on DSA, symptom resolution, procedure-related complications, and the rate of complete fistula occlusion on follow-up DSA. RESULTS:Twenty-three patients (mean age 57 years; 74% female) underwent endovascular treatment for carotid-cavernous fistulas, including 11 direct and 12 indirect lesions. The most common presenting symptoms were proptosis and orbital pain. Coil embolization was used in all cases, with adjunctive materials in 44% (10/23). Immediate complete occlusion was achieved in 48% (11/23) and complications occurred in 9% (2/23). Final follow-up DSA showed complete fistula closure in 91.3% of patients (21/23). Clinical improvement was achieved in 91.3% (21/23) of the cohort, with complete clinical resolution in 14 patients (61%). CONCLUSIONS:The results of our study suggest that long-term radiological and clinical outcomes in patients with CCFs treated with endovascular embolization were very satisfactory across all fistula types. Therefore, modern endovascular methods should be considered during the multidisciplinary evaluation of these patients.
INTRODUCTION:Anti-CD20 monoclonal antibodies are widely used as high-efficacy treatment agents (HETAs) in multiple sclerosis (MS). In patients treated with ocrelizumab (OCR), reduced serum IgG levels are a common laboratory abnormality. Infections are among the most frequently observed adverse events during OCR therapy. MATERIAL AND METHODS:We analyzed the humoral immune response during OCR therapy in 52 people with multiple sclerosis (PwMS) and assessed the safety of this treatment, including treatment-related adverse events and infection rates over a period of up to six years. RESULTS:After three years of treatment, immunoglobulin G (IgG) and IgG1 levels decreased, particularly in the relapsing-remitting MS (RMS) group. Higher body mass index (BMI) was associated with lower Ig levels and greater CD19+ cell depletion. Infections were more frequent in patients with relapses within 3 months prior to OCR initiation. Clinical implications/future directions. Ocrelizumab treatment for up to six years showed a manageable safety profile. Given the higher infection risk in patients with greater disease activity, earlier HETA initiation may be beneficial. The association between higher BMI and CD19+ cell depletion warrants further study to support personalized OCR dosing strategies.
INTRODUCTION:Our aim was to identify Parkinson's disease (PD) patients with overflow incontinence and to observe trends between pre- and post-void residual volume (PVR) and urinary urgency, incontinence or nocturia in our sample. MATERIAL AND METHODS:As part of our diagnostic evaluation, we measured PVR using a portable bladder scanner in patients with PD at our inpatient facility. The initial measurement was conducted upon admission, and, if increased (PVR > 50 mL), a control measurement was carried out on the same or following day. If the PVR was ≥ 150 mL at follow-up, further control measurements were made immediately before and after micturition. Data on urinary urgency, urinary incontinence and nocturia were retrieved from the non-motor symptoms (NMS) part of the standardized medical history taken at admission. RESULTS:We identified 117 PD patients with increased PVR (≥ 150 mL) during the 8-month period. Due to limited mobility, cognitive impairment, lack of compliance, or early discharge, we were able to carry out the measurements in only 23 out of 117 patients. The investigated population consisted of these 23 PD patients. Further control measurements were carried out to exclude overflow incontinence. We identified no patients with overflow incontinence in our sample. We found that the voiding volume and the volume before voiding were the highest in the urinary urgency group (234.1 mL and 148.3 mL, respectively), while the PVR was the highest among patients with nocturia (91.9 mL vs. 85.8 mL in urgency and 86.6 mL in incontinence). Notable differences in pre-void, post-void, and voiding volumes were observed between men and women in all subgroups, in favor of male patients in our male-dominant sample. Urinary urgency was the most prevalent (78.3%) lower urinary tract symptom (LUTS), followed by nocturia (65.2%) and urinary incontinence (34.8%). We initially hypothesized a possible association between high PVR and urinary urgency in PD patients, but this could not be confirmed. Although the initial PVR was ≥ 150 mL, repeated controls showed lower values, underlining the importance of PVR controls in PD patients. The average age of the patients with nocturia was somewhat higher and they had higher UPDRS III scores than patients in the other subgroups. We only observed slight differences across the subgroups with regard to pre-void, post-void, and voiding volumes. CONCLUSION:The strength of the evaluation is limited by the relatively small sample size. Further studies are needed to clarify the characteristics and possible associations of LUTS subgroups (urgency, incontinence, and nocturia) in PD patients with high PVR.
AIM OF THE STUDY:This study assessed the triglyceride-glucose (TyG) index for differentiating between Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP), and its association with cognitive profiles and clinical status. MATERIAL AND METHODS:This retrospective cross-sectional study involved 329 patients (272 PD, 15 MSA, 42 PSP). Assessments included motor and non-motor symptoms, the TyG index, and metabolic profiles. RESULTS:The TyG index did not differentiate PD from AP; however, PSP patients exhibited significantly lower fasting glucose levels than the PD and MSA groups (p < 0.05). The TyG index and lipid profiles did not differ significantly (p > 0.05) among the three groups. Cognitive function (Addenbrooke's Cognitive Examination III, ACE-III) was notably lower in PSP than in MSA and PD (p = 0.0019), especially in memory and fluency, while depressive symptoms (Beck Depression Inventory, BDI) remained similar (p = 1.0). CONCLUSIONS AND CLINICAL IMPLICATIONS:The TyG index is not a reliable method for differentiating PD from atypical parkinsonism. Lower fasting glucose levels in PSP serve as a potential "red flag" associated with cognitive decline. Future research should incorporate homeostatic model assessment of insulin resistance (HOMA-IR) and continuous glucose monitoring to further explore these metabolic associations.
AIM OF THE STUDY:To evaluate electrophysiological parameters of central nervous system (CNS) function in patients with non-small-cell lung cancer (NSCLC) without detectable CNS metastases. CLINICAL RATIONALE FOR THE STUDY:Early recognition of nervous system involvement in lung cancer (LC) is important for the management of the disease. Evoked potentials are an objective and noninvasive method for assessing CNS bioelectrical activity, regarded as a useful tool in revealing subclinical CNS dysfunction in systemic diseases, including neoplasms. MATERIAL AND METHODS:The study included 11 patients (mean age 67.3 years, 55% females), diagnosed with NSCLC, without CNS metastases, and a group of 24 healthy controls (HC) matched for age. All participants underwent brainstem auditory evoked potentials (BAEP), visual evoked potentials (VEP) and electroencephalography (EEG). Parameters of VEP and BAEP were compared between LC patients and HC. In the NSCLC group, they were also referred to the disease outcome evaluation after 12 months of follow-up. RESULTS:In VEPs, patients with NSCLC had significantly longer median P100 and N145 latencies compared to the HC (112 vs. 104 ms, p < 0.001 and 158 vs. 145 ms, p = 0.002, respectively). In BAEPs, longer median latency of wave V and I-V interpeak latency were found in NSCLC patients (5.88 vs. 5.80 ms, p = 0.047 and 4.19 vs. 4.05 ms, p = 0.007, respectively); they also had significantly lower median amplitudes of I and V waves (0.13 vs. 0.25 μV, p < 0.001 and 0.29 vs. 0.39 μV, p = 0.001, respectively). In total, 10 out of 11 patients showed abnormalities in either VEP or BAEP: in 4 patients, delayed latencies or decreased amplitudes were detected for both modalities, in 4, only in BAEP and in 2, only in VEP. EEG abnormalities were detected in two patients in the NSCLC group. After 12 months of follow-up, in none of the patients brain metastases were revealed. CONCLUSIONS AND CLINICAL IMPLICATIONS:This exploratory study demonstrated abnormalities of EP parameters in NSCLC patients, without otherwise detectable CNS involvement. These findings may suggest subclinical brain dysfunction in the course of NSCLC, although the underlying mechanism remains uncertain. The usefulness of electrophysiological methods in monitoring or predicting subtle neurological complications of NSCLC warrants further investigation.
INTRODUCTION:Late-onset CSF1R-related disorder is an ultra-rare neurogenetic disorder caused by pathogenic variants in the colony-stimulating factor 1 receptor (CSF1R) gene. Due to the rapid disease progression and rapid deterioration of neuropsychological status of affected individuals, prompt and accurate diagnosis is essential. This report aims to highlight the need for clinicians to consider this differential diagnosis in patients with a rapidly progressive clinical course of multiple sclerosis (MS). MATERIAL AND METHODS:We report the case of an adult male presenting with rapidly progressive neurological deficits initially attributed to MS. Serial neuroimaging demonstrated progressive enlargement of hyperintense white matter lesions, correlating with marked clinical deterioration despite ongoing treatment. Genetic evaluation performed because of the aggressive disease course revealed a previously reported in a single patient variant in the CSF1R gene (c.2549C > T; p.Ser850Leu), located within the critical tyrosine kinase domain (TKD) of the receptor. In silico analysis, together with the patient's clinical phenotype, supported classification of this variant as likely pathogenic. CONCLUSION:This case underscores the importance of considering CSF1R-related disorder not only in the differential diagnosis of adult-onset leukoencephalopathies but also in patients with rapidly progressive MS-like disease. Identification and characterization of novel variants contribute to expanding genotype-phenotype correlations in late-onset CSF1R-related disorder and highlight the crucial role of genetic testing in atypical MS cases.
INTRODUCTION:Sacroiliac joint (SIJ) dysfunction is an underrecognized source of lumbosacral and leg pain. Manual therapy targeting SIJ hypomobility/blockage may rapidly reduce pain and disability, yet pragmatic outcome data remain limited. MATERIAL AND METHODS:We conducted a single-center observational cohort study of 100 consecutive adults (73% women; mean age 49.16 ± 14.28 years; BMI 25.99 ± 4.15 kg/m²) with lumbosacral and/or radicular leg pain attributed to SIJ dysfunction. Eligibility required cross-sectional imaging (CT/MRI) and ≥ 3 positive SIJ provocation tests (e.g., Patrick/FABER, Mennell, thigh thrust, Yeoman's, SIJ compression, hip rotation). All patients received a standardized SIJ manipulation protocol (up to three sessions, 7-day intervals) administered by the same physiotherapist. Pain intensity on the Numerical Rating Scale (NRS) was measured at baseline, after each session, and at 3 months; disability was assessed with the Oswestry Disability Index (ODI). Nonparametric statistics were prespecified (Shapiro-Wilk test for normality; Friedman test with Kendall's W and Holm-adjusted Wilcoxon post hoc test for repeated NRS; Wilcoxon signed-rank test for ODI; α < 0.05). RESULTS:The most frequent abnormal finding was the Mennell sign (clinical finding, 100%); key provocation tests were commonly positive [thigh thrust 89%, Mennell (provocation) test 81%, Yeoman's test 52%]. Median NRS decreased from 8 (IQR: 7-9) at baseline to 1 (IQR: 0-3) after the first manipulation, 0 (IQR: 0-0) after the second and third, and 0 (IQR: 0-2) at 3 months (Friedman p < 0.001). ODI improved from 30 (IQR: 25-35) to 7 (IQR: 6-9; p < 0.001), with significant gains across all domains (all p < 0.001) at 3 months. CONCLUSIONS:In carefully triaged patients with suspected SIJ-mediated pain, a short, standardized SIJ manipulation sequence was associated with large, rapid, and sustained improvements in pain and disability through 3 months. These pragmatic data complement prior trials and support considering SIJ manipulation as a low-cost, repeatable option within conservative care pathways. Randomized, assessor-blinded studies with longer follow-up are warranted to confirm causality and identify likely responders.
AIM OF THE STUDY:To determine the frequency of colony-stimulating factor 1 receptor gene (CSF1R) variants in a cohort of Mayo Clinic patients with different neurodegenerative disorders. MATERIAL AND METHODS:Blood samples collected from patients diagnosed in the past five years with early-onset (18-60 years) cognitive impairment, atypical parkinsonism and primary progressive multiple sclerosis (PPMS) were screened for variants in the CSF1R gene using Sanger sequencing. For individuals with CSF1R variants, clinical data were analyzed. An online tool, SIFT (https://sift.bii.a-star.edu.sg/), was applied to predict possible impact of CSF1R variants. Moreover, the identified CSF1R variants were expressed in HEK293 cells, and their effects on CSF1R phosphorylation were assessed by western blotting. RESULTS:Samples from 310 patients with dementia (n = 135), PPMS (n = 96) and atypical parkinsonism (n = 79) were analyzed. Two novel CSF1R variants in the heterozygous state were identified: p.G872V (c.2615G > T) in a 60-year-old male with atypical parkinsonism and moderate microangiopathic leukoencephalopathy on MRI and p.K864Q (c.2590A > C) in a 45-year-old female with behavioral variant of frontotemporal lobar degeneration with extensive tau pathology who died by suicide. The latter patient was also a carrier of a MAPT gene mutation: p.N279K; c.837T > G. SIFT analysis predicted both CSF1R variants to be deleterious. Both patients had a positive family history for dementia. In vitro studies confirmed that both CSF1R p.K864Q and p.G872V variants disturbed CSF1R phosphorylation with a stronger effect for CSF1R p.G872V. CONCLUSIONS AND CLINICAL IMPLICATIONS:CSF1R-related disorder (RD) is often mis- and underdiagnosed. Genetic testing for CSF1R-RD should be applied more often in cases of early-onset neurodegenerative disorders with a combination of cognitive, psychiatric, and motor symptoms and a positive family history.
INTRODUCTION:Multiple sclerosis (MS) is a disease of the central nervous system (CNS) with a complex pathogenesis characterized by inflammation, demyelination, and progressive neurodegeneration. Cognitive impairment (CI) is a common manifestation of MS, with a prevalence ranging from 40% to 70% of patients. It also appears to be one of the factors involved in deterioration of work ability, which negatively affects patients' independence and carries a substantial socioeconomic burden. MATERIAL AND METHODS:We aimed to summarize the most recent findings regarding the relationship between CI and employment status in MS. PubMed and Embase were searched in accordance with PRISMA guidelines, which resulted in the inclusion of the 37 most appropriate studies. RESULTS:Patients with MS scored significantly worse on cognitive assessment tests than healthy controls. Significant correlations were found between worse performance in different cognitive domains and unemployment. Moreover, some studies reported that CI may also predict future vocational deterioration in patients with MS. CONCLUSIONS:Cognitive dysfunction may play an important role in the deterioration of employment status among patients with MS. Of the analyzed neuropsychological tests, the Symbol Digit Modalities Test (SDMT) appears to be the most suitable tool for cognitive evaluation in this patient group.
AIM OF THE STUDY:This study aims to define the clinical and neuropathological features associated with the CSF1R c.2381T > C, p.Ile794Thr variant. CLINICAL RATIONALE FOR THE STUDY:Colony-stimulating factor 1 receptor (CSF1R)-related disorder (CSF1R-RD) is a rare, fatal, autosomal dominant leukoencephalopathy caused by mutations in the CSF1R gene, primarily affecting microglial function. The CSF1R c.2381T > C, p.Ile794Thr variant in exon 18 is the most frequently reported pathogenic mutation worldwide. The clinical presentation of carriers of different CSF1R mutations may vary. MATERIAL AND METHODS:We analyzed medical records and neuropathology of seven patients from four families evaluated at Mayo Clinic Florida (MCF). We compared them with 74 previously reported p.Ile794Thr cases identified through a systematic literature search (PubMed, Embase, Web of Science, and Google Scholar) up to January 2026. Data on age of onset, clinical symptoms, survival, and imaging findings were analyzed. Haplotype analysis was performed to investigate potential founder effects. RESULTS:Parkinsonism occurred significantly more frequently in the MCF cohort than in the p.Ile794Thr cases reported in the literature (85.7% vs. 40.0%; p = 0.04). Haplotype analysis indicated that the mutation likely arose independently in different lineages rather than from a common ancestor, including a confirmed de novo case. Neuropathological evaluation confirmed classic hallmarks of CSF1R-RD: white matter degeneration, axonal spheroids, and pigmented glia. CONCLUSIONS AND CLINICAL IMPLICATIONS:CSF1R-RD associated with the p.Ile794Thr variant presents a consistent clinical phenotype across cases reported globally, though the prevalence of parkinsonian features may vary by population. The high frequency of this variant across diverse haplotypes suggests a mutational hotspot in exon 18.
