OBJECTIVE: Diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL) is an aggressive B-cell lymphoma with clinical and molecular heterogeneity. Primary CNS-DLBCL (PCNSL) affects the brain, eyes, leptomeninges, or spinal cord without systemic involvement. Secondary CNS-DLBCL (SCNSL) manifests concurrently with systemic lymphoma or as an isolated CNS relapse with poor prognosis.
METHODS: Next-generation sequencing (NGS) was used to identify genomic alterations in 32 PCNSL and 9 SCNSL cases. Single nucleotide variants and copy number variations in addition to the clinicopathologic data and proposed risk predictive values were compared to aid in diagnostic differentiation between the two types of lymphomas.
RESULTS: The MCD genotype, characterized by mutations in MYD88 and CD79B, is the most common alteration in PCNSL and is associated with lower survival rates. The frequency of MYD88 mutation was significantly higher in PCNSL compared to SCNSL (75.0% vs. 33.3%; p=0.042). Recurrent copy number loss of 6p21 occurred in 56.1% of cases, more often in PCNSL (65.6%) than in SCNSL (22.2%) (p=0.028). Diagnostic positive predictive values (PPV) of MYD88 mutation and 6p21 loss for PCNSL were 89% and 91%, respectively. PPV of both alterations was 93% for the diagnosis of PCNSL.
CONCLUSIONS: MYD88 mutation and 6p21 loss were significantly higher in PCNSL than in SCNSL, and novel risk prediction models based on these distinct genomic profiles can aid in the clinical differentiation of PCNSL and SCNSL.

Background: type 1 neurofibromatosis (NF1) is the most common neurocutaneous disorder, and it is an inherited condition that causes a tumour predisposition. Central nervous system (CNS) manifestations are a significant cause of morbidity and mortality in NF1. We provide a pictorial review of neuroradiological features of NF1, with emphasis on magnetic resonance imaging (MRI), and we assess the frequency of those features on a cohort of NF1 patients. Methods: we retrospectively evaluated all patients with a diagnosis of NF1 who underwent MRI of the spine and brain in our centre over a period of almost 5 years. A total of 74 patients were enrolled, 28 males and 46 females, with a mean age of 21 ± 12.67 years. The frequency of CNS manifestations encountered in our cohort of NF1 patients was assessed and compared with the data found in other studies published in the literature. Results: many of our findings were in line with the literature, and possible interpretations for those that turned out to be different were suggested in the discussion. Conclusion: imaging plays a central role in the diagnosis and management of NF1, and the knowledge of CNS manifestations could be critical for its early detection and identification, such as for treatment planning and prognostic implications.

BACKGROUND: Tick-borne encephalitis (TBE) is a human viral infectious disease involving the central nervous system (CNS). It is caused by the tick-borne encephalitis virus (TBEV). At present, there is very limited information regarding the clinical importance and health burden of TBE infections without signs of CNS inflammation. Moreover, such cases are omitted from official TBE surveillances and there are no reports of population-based studies.
RESULTS: A nationwide population-based study was conducted in Latvia by intensively searching for symptomatic TBEV infections recorded in outpatient and hospital settings between 2007 and 2022. In total, 4,124 symptomatic TBEV infections were identified, of which 823 (20.0%) had no CNS involvement. Despite the lack of neurological symptoms, non-CNS TBE patients still experienced severe health conditions that required management in a hospital setting for a median duration of 7 days. Furthermore, lumbar puncture information was available for 708 of these patients, with 100 (14.1%) undergoing the procedure, suggesting a high suspicion of CNS involvement.
CONCLUSIONS: Clearly, non-CNS TBE has the potential to negatively impact the health of patients. The actual burden of non-CNS TBEV cases may be higher than we think as these cases are omitted from official TBE surveillances and are challenging to recognize.

Previous studies have raised concerns about the effects of oral propranolol on the central nervous system in infants, the exact measure and mechanism and the long-term follow-up of which is less well studied. This was an ambispective comparative study of children with infantile haemangioma (IH) followed by a repeat visit 4-10 years after completion of propranolol therapy. Parents were asked about psychologic functioning along with an initial screening examination. All patients were evaluated by a paediatric psychiatrist. After evaluation by the Strength and Difficulties Questionnaire, and subsequently by the paediatric psychiatrist, 2 of 12 patients (16.67%) showed features of attention deficit hyperactivity disorder in comparison to 0 of 40 subjects in the control group (0.0498; α = 0.05). These results indicate an increased risk of neuropsychiatric illnesses such as attention deficit hyperactivity disorder (ADHD) in patients given propranolol for IH, as supporting evidence to previous claims.

UNASSIGNED: Several previous studies have reported an association between rheumatoid arthritis (RA) and epilepsy, but the causal relationship is unclear. The aim of this study was to assess the connection between RA and epilepsy in a European population using Mendelian randomization (MR).
UNASSIGNED: Genome-wide association study summary data on RA and epilepsy from European populations were included. Univariate MR (UVMR) and multivariate MR were used to investigate the causal relationship between the two conditions. Three analysis methods were applied: inverse variance weight (IVW), MR-Egger, and weighted median, with IVW being the primary method. Cochran Q statistics, MR-PRESSO, MR-Egger intercept, leave-one-out test, and MR-Steiger test were combined for the sensitivity analysis.
UNASSIGNED: UVMR showed a positive association between RA and epilepsy risk (OR=1.038, 95% CI=1.007-1.038, p=0.017) that was supported by sensitivity analysis. Further MVMR after harmonizing the three covariates of hypertension, alcohol consumption, and smoking, confirmed the causal relationship between RA and epilepsy (OR=1.049, 95% CI=1.011-1.087, p=0.010).
UNASSIGNED: This study demonstrated that RA is associated with an increased risk of epilepsy. It has emphasized that the monitoring of epilepsy risk in patients diagnosed with RA should be strengthened in clinical practice, and further studies are needed in the future to explore the potential mechanism of action connecting the two conditions.

UNASSIGNED: This study aims to determine the possible embryotoxic effects of propofol on the cerebellum and spinal cord using fertile chicken eggs.
UNASSIGNED: A total of 430 fertile eggs were divided into 5 groups: control, saline, 2.5 mg.kg-1, 12.5 mg.kg-1, and 37.5 mg.kg-1 propofol. Injections were made immediately before incubation via the air chamber. On the 15th, 18th, and 21st day of incubation, 6 embryos from each group were evaluated. Serial paraffin sections taken from the cerebellum and spinal cord were stained with hematoxylin-eosin, Kluver-Barrera, toluidine blue, and periodic acid-Schiff\'s reaction. The outer granular layer and total cortex thickness were measured, and the linear density of the Purkinje cells was determined. The ratios of the substantia grisea surface area to the total surface area of the spinal cord were calculated. The transverse and longitudinal diameters of the canalis centralis were also assessed.
UNASSIGNED: No structural malformation was observed in any embryos examined macroscopically. No significant difference was observed between the groups in terms of development and histologic organization of the cerebellum and spinal cord. However, on the 15th, 18th, and 21st day, the outer granular layer (p < 0.001 for all days) and the total cortex thickness (p < 0.01, p < 0.001, and p < 0.001, respectively) decreased significantly in different propofol dose groups in varying degrees in the cerebellum. Similarly, in the spinal cord, there were significant changes in the ratios of the substantia grisea surface area to the total surface area (p < 0.01 and p < 0.001, respectively).
UNASSIGNED: It was concluded that the in-ovo-administered propofol given immediately before incubation has adverse effects on the developing cerebellum and spinal cord. Therefore, it is important for anesthesiologists always to remain vigilant when treating female patients of childbearing age.

Objectives To assess the association between concomitant use of central nervous system drugs and femoral fracture risk in individuals ≥80 years old in Japan. Methods A case-crossover design was used, defining the case period as 3 days before the fracture diagnosis and the control period as 31-33, 34-36, and 37-39 days prior. The association between the daily intake of central nervous system drugs (Anatomical Therapeutic Chemical codes) and fracture risk was analyzed using conditional logistic regression. Patients Using the Japanese administrative claims database, we examined elderly patients diagnosed with femoral neck fractures between January 1, 2009, and December 31, 2020. Results In 255,875 patients, the concomitant use of central nervous system drugs increased the odds ratios of femoral fracture (3.41[95% confidence interval: 3.27-3.55], 3.69 [3.46-3.91], 3.76 [3.42-4.13], and 4.34 [3.86-4.86] for an intake of >0-1, >1-2, >2-3, and >3 central nervous system drugs, respectively). Conclusions The concomitant use of central nervous system drugs is associated with an increased risk of femoral fractures in individuals ≥80 years old in Japan.

Objective: Neuroendocrine tumors (NETs) are neoplasms that primarily occur in the lungs, appendix, small intestine, pancreas, and rectum, and typically metastasize to the liver or lymph nodes. However, in rare cases NETs can originate in the central nervous system (CNS). Understanding primary CNS NET neuropsychological manifestations aids in recommendations for neurocognitive follow-up, treatment and lifestyle planning, and future research. Method: Given the dearth of neuropsychological research for CNS NETs, we present a case seen in a 43-year-old woman. Results: Initial and 8-month follow-up neuropsychological evaluations of the patient revealed a Major Neurocognitive Disorder where the pattern of findings was consistent with tumor location and additional treatment-related factors. Reliable change indices at her re-evaluation revealed declines in verbal and visual memory, with statistical, yet not clinical, improvements in different domains. Follow-up monitoring of comprehensive care continued to occur after neuropsychological evaluations. Conclusions: This case study assists in the characterization of initial and follow-up neuropsychological presentation of a primary CNS NET, where evaluations helped inform clinical care and functional recommendations. This case demonstrates the importance for neuropsychologists to have awareness of various conditions, even rare conditions, which can inform a systematic approach to research and clinical care with neuro-oncological populations.

BACKGROUND: In the context of severe unexplained haemorrhage (SH), it is usual to seek haematological evaluation and investigate for an inherited rare bleeding disorder (IRBD). In such circumstances, appropriate screen can discriminate between IRBD and suspected child abuse. Yet, little information is available about the frequency of SH in the population of patients with IRBD.
OBJECTIVE: To collect epidemiologic data about SH and IRBD.
METHODS: The database of the FranceCoag network has collected information about IRBD since January 2004. Based on data gathered up to 16 March 2022, a retrospective search was conducted for of SH events having occurred before or at the time of IRBD diagnosis. Demographics and diagnosis circumstances were retrieved, as well as information about SH, defined as any life-threatening bleeding or intracranial haemorrhage.
RESULTS: Among the 13,433 patients of the database, 109 (0.8%) fulfilled inclusion criteria including a known date of IRBD diagnosis, haemophilia A or B (HA/HB) being the most frequent (82.5%). IRBD was discovered as a consequence of an SH event in 82.6% of the cases while CNS was involved in 55%. Severe and moderate HA/HB and other severe IRBD presented significantly more intracranial haemorrhage (p < .02) and a lower age at diagnosis (p = .03).
CONCLUSIONS: These data support that any unusual SH should raise a suspicion of IRBD. Particularly before 1-year of age, it is suggested to first confirm moderate or severe haemophilia and severe IRBD by standard coagulation tests (APTT, PT and fibrinogen), combined with a clotting FXIII assay as first-line investigation. Subsequent assays of coagulation factors should be performed in the case of abnormal values, in second-line investigation.

BACKGROUND: Knee pain is a prominent concern among older individuals, influenced by the central nervous system. This study aimed to translate the Central Aspects of Pain in the Knee (CAP-Knee) questionnaire into Japanese and investigate its reliability and validity in older Japanese individuals with knee pain.
METHODS: Using a forward-backward method, CAP-Knee was translated into Japanese, and data from 110 patients at an orthopedic clinic were analyzed. The Japanese version (CAP-Knee-J) was evaluated regarding pain intensity during walking, central sensitization inventory, and pain catastrophizing scale. Statistical analyses confirmed internal validity and test-retest reliability. Concurrent validity was assessed through a single correlation analysis between CAP-Knee-J and the aforementioned measures. Exploratory factor analysis was employed on each CAP-Knee-J item to examine structural validity.
RESULTS: CAP-Knee-J showed good internal consistency (Cronbach\'s α = 0.86) and excellent test-retest reliability (intraclass correlation coefficient = 0.77). It correlated significantly with pain intensity while walking, central sensitization inventory scores, and pain catastrophizing scale scores. Exploratory factor analysis produced a three-factor model.
CONCLUSIONS: CAP-Knee-J is a reliable and valid questionnaire for assessing central pain mechanisms specific to knee pain in older Japanese individuals, with moderate correlations with the CSI and weak with the PCS, thus indicating construct validity. This study supports the development of effective knee pain treatments and prognosis predictions.