BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) are cerebrovascular dysregulation syndromes, and an overlapping spectrum may exist. We aimed to ass...BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) are cerebrovascular dysregulation syndromes, and an overlapping spectrum may exist. We aimed to assess the frequency and features of PRES and RCVS overlaps. METHODS: We retrospectively included patients diagnosed with PRES or RCVS from our tertiary center during 2008-2018. Subgroups of PRES with vasoconstriction and RCVS with resolving vasogenic brain edema were defined as the overlap group. Inter-group comparisons were performed for clinical, radiological, and laboratory features. RESULTS: Of 360 patients (mean age 48 years, 73% female), 242 were diagnosed with PRES, 83 with RCVS, and 35 patients had overlapping features. In the overlap group, ischemic infarcts (31%) and intraparenchymal hemorrhage (34%) were more frequent than in isolated RCVS (15%, p = 0.03, and 11%, p < 0.01) or isolated PRES (12% and 13%, p-values <0.01). Subarachnoid hemorrhage was more common in overlap (17%) than in isolated PRES (5%, p = 0.006), but similar to isolated RCVS (25%, p = 0.337). Distal vascular segments were most involved (>50%) by vasoconstriction in RCVS and overlap cases. Neutrophil-to-lymphocyte ratio was higher in overlap (7.4) than in RCVS (2.7, p = 0.02), but similar to PRES (7.4). Most patients had a favorable discharge disposition (home or acute rehabilitation). There was one death (1%) with RCVS, one with overlap (3%), and 17 (7%) with PRES. CONCLUSIONS: Although more distinct clinical and radiological features exist in typical RCVS and PRES, an overlapping presentation is not uncommon. Overlap may be associated with more ischemic and hemorrhagic complications, but mostly resembles the parent condition.
BACKGROUND: The p.V142I (V122I) transthyretin variant (TTRv) is the most common amyloidogenic TTRv in the United States, particularly among Black people. While p.V142I ATTRv is primarily associated with cardiac amyloidos...BACKGROUND: The p.V142I (V122I) transthyretin variant (TTRv) is the most common amyloidogenic TTRv in the United States, particularly among Black people. While p.V142I ATTRv is primarily associated with cardiac amyloidosis, the prevalence and attribution of polyneuropathy (PN) to amyloidosis in individuals with this variant are poorly defined. OBJECTIVE: To determine the prevalence of PN in individuals with the p.V142I TTRv, evaluate how often PN is attributable to ATTRv amyloidosis rather than alternative comorbid conditions, and compare p.V142I TTRv to non-p.V142I TTRv individuals. METHODS: We conducted a retrospective review of patients with TTRv evaluated at the Penn Amyloidosis Center of the University of Pennsylvania in Philadelphia between 2021 and 2025. Patients who underwent a comprehensive neurologic and cardiac assessment were selected. PN was classified as possible, probable, or definite based on clinical symptoms, examination, and diagnostic testing. PN attribution to amyloidosis was determined using clinical judgment and categorized as unlikely, possible, probable, or definite. RESULTS: Of 153 patients with TTRv who underwent a comprehensive neurologic and cardiac assessment, 82 carried the p.V142I variant. Among these, 41% were found to have PN; 13% had PN possibly or probably attributable to amyloidosis. In the subgroup with confirmed cardiac amyloidosis, 35% had PN possibly or probably attributable to amyloidosis. Comorbid conditions such as diabetes, chronic kidney disease, alcohol use, and neurotoxic medication exposure were common, and often provided alternative explanations for the PN. CONCLUSIONS: Although PN is present in over 40% of individuals with the p.V142I TTRv, it is often unrelated to amyloidosis. Accurate attribution is critical to avoid misdiagnosis and overtreatment. In populations with high burdens of comorbidities and health care disparity, cautious interpretation and selective use of confirmatory testing are essential for appropriate management.
OBJECTIVE: To evaluate the association between statin use, disease progression, and survival in patients with amyotrophic lateral sclerosis (ALS) using data from the Pooled Resource Open-Access ALS Clinical Trials (PRO-A...OBJECTIVE: To evaluate the association between statin use, disease progression, and survival in patients with amyotrophic lateral sclerosis (ALS) using data from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. METHODS: We conducted a retrospective cohort study of adults (≥18 years) diagnosed with ALS and included in the PRO-ACT database. Statin exposure was defined as any statin use at cohort entry. Statin users were matched 1:1 to non-users using propensity score matching based on age, baseline ALS Functional Rating Scale (ALSFRS), disease duration, ethnicity, bulbar onset, riluzole use, and cardiovascular or metabolic comorbidities. Participants were followed from cohort entry or statin initiation until death, end of follow-up (36 months), or loss to follow-up. The primary outcome was all-cause mortality at three years. The secondary outcome was disease progression, defined as time to a four-point decline in ALSFRS score. Cox proportional hazards models were used to estimate hazard ratios (HRs). RESULTS: Among 3439 eligible participants, 131 statin users (mean age 63.1 years; 34% female) were identified and matched to 131 non-users. Statin use was not associated with all-cause mortality at three years (HR 0.97; 95% CI 0.66-1.44; P = 0.89). Disease progression was also similar between statin users and non-users (HR 1.02; 95% CI 0.80-1.31; P = 0.90). CONCLUSIONS: In this large observational cohort, statin use was not associated with survival or disease progression in ALS. These findings do not support statin initiation or discontinuation based solely on ALS diagnosis or disease course.
Duchenne muscular dystrophy (DMD) is the most common and severe muscle disorder in children, primarily affecting boys, with an incidence of 1 among 5000. This X-linked recessive disease is marked by progressive muscle wa...Duchenne muscular dystrophy (DMD) is the most common and severe muscle disorder in children, primarily affecting boys, with an incidence of 1 among 5000. This X-linked recessive disease is marked by progressive muscle wasting, leading to loss of ambulation, respiratory impairment, and cardiomyopathy, with symptoms appearing between ages 2 and 5. While advances in care have extended the life expectancy of DMD patients to 30-40 years, cardiac and respiratory failure often leads to mortality by age 40. DMD is caused by mutations in the DMD gene, encoding the dystrophin protein, essential for muscle fiber integrity. Some studies performed between the 1980s and 1990s reported significant cellular radiosensitivity in DMD cells, though the mechanisms remained unclear. As a first approach, we investigated whether our Radiation-Induced ATM Nucleo-Shuttling (RIANS) model that describes individual molecular and cellular responses to radiation in fibroblasts of different origins may be also relevant for DMD fibroblasts. We observed moderate but significant cellular radiosensitivity, a high yield of micronuclei, and delayed ATM nucleo-shuttling, indicating impaired DNA double-strand breaks recognition. This delay may be consistent with the sequestration of ATM around the nucleus by mutated dystrophin, forming pATM perinuclear crowns, an accelerated aging biomarker. Such data provide a unified molecular and cellular characterization of radiation response in DMD fibroblasts that should be investigated further.
Donofrio PD, Gorson KC, Hofman E
… +10 more, Karam C, Kira JI, Kostera-Pruszczyk A, Léger JM, Nobile-Orazio E, Attarian S, Markov M, Tse A, De Roeck A, Lewis RA
BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare, acquired, immune-mediated polyneuropathy that is commonly misdiagnosed. The global, pivotal ADHERE trial pioneered the use of a diag...BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare, acquired, immune-mediated polyneuropathy that is commonly misdiagnosed. The global, pivotal ADHERE trial pioneered the use of a diagnostic adjudication committee (DAC) to verify accurate CIDP diagnosis for potential participants. METHODS: The committee consisted of nine independent experts with extensive experience in CIDP diagnosis, trained to review existing evidence for CIDP in patient medical records. Enrollment eligibility was confirmed when 2 of 2 adjudicators agreed on a definite or probable CIDP diagnosis, as defined by the 2010 European Federation of Neurological Societies-Peripheral Nerve Society criteria (2/2 agreement; phase 1). Participants were not enrolled if both adjudicators determined that the eligibility criteria were not met. When the two adjudicators disagreed, a third adjudicator (the DAC Chair or designee) provided a 2 out of 3 majority vote (phase 2). RESULTS: Of the 560 cases reviewed, 391/560 (69.8%) were determined to have definite/probable CIDP and 169/560 (30.2%) did not meet diagnostic eligibility for ADHERE. Of all enrolled participants with phase 1 adjudication data (n = 340), 277 (81.5%) were confirmed with a 2/2 agreement on diagnostic eligibility (phase 1); 50 participants who were determined to have definite/probable CIDP failed other inclusion/exclusion criteria and were not eligible for ADHERE. The top reasons for disagreement between adjudicators in phase 1 were differences in assessment of clinical and electrodiagnostic criteria. CONCLUSION: Use of a DAC addressed the limitation of CIDP misdiagnosis and increased the likelihood that the ADHERE trial included participants with confirmed CIDP.
BACKGROUND: Performance of Parkinson's Disease Multidisciplinary Complex Therapy in specialized units is quite common in Germany. Data on the benefit of this hospitalisation approach in conjunction with standardised perf...BACKGROUND: Performance of Parkinson's Disease Multidisciplinary Complex Therapy in specialized units is quite common in Germany. Data on the benefit of this hospitalisation approach in conjunction with standardised performance of instrumental tests are rare. OBJECTIVES: To evaluate the outcome in 271 consecutively referred patients with Parkinson's disease. METHODS: Disease severity was scored in combination with execution of standardised instrumental procedures in after admission and before discharge. RESULTS: Rating scale scores and test outcomes of simple, repetitive and complex movement series execution improved. There were high correlation coefficients between the applied various evaluations at the two assessment moments. Computed differences of the instrumental test results between both valuation timepoints were weakly associated to each other. CONCLUSION: The used approach of combined subjective and objective evaluation mirrors the achieved benefit. This concept is suitable to convince payers on the positive effects of this kind of in-patient stays, which also reduces caregiver burden.