Seizures in children undergoing stem cell transplantation Turón‐Viñas, Eulalia; López‐Torija, Iván; Coca‐Fernández, Elisabet ...
Pediatric transplantation,
February 2024, 2024-Feb, 2024-02-00, 20240201, Letnik:
28, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background
Neurological complications (NCs) are of major concern following hematological stem cell transplantation (HSCT), most of which present with seizures.
Procedures
We performed a retrospective ...study (2002–2018) of patients undergoing HSCT in order to analyze the incidence and aetiologies related to seizures.
Results
Of 155 children undergoing HSCT, 27 (17.4%) developed seizures at some point in 2 years of follow‐up. The most frequent etiologies were central nervous system (CNS) infection (n = 10), drug toxicity (n = 8), and vascular disease (n = 5). A statistically significant association was found between seizure and the HSCT type (lower risk for a related identical donor, p = .010), prophylactic or therapeutic mycophenolate use (p = .043 and .046, respectively), steroid use (p = .023), selective CD45RA+ depletion (p = .002), pre‐engraftment syndrome (p = .007), and chronic graft‐versus‐host disease (GVHD) severity (p = .030). Seizures predicted evolution to life‐threatening complications and admission to intensive care (p < .001) and higher mortality (p = .023). A statistically significant association was also found between seizures and sequelae in survivors (p = .029). Children who developed seizures had a higher risk of CNS infection and vascular disease (odds ratio 37.25 95% CI: 7.45–186.05 and 12.95 95% CI 2.24–74.80, respectively).
Conclusions
Neurological complications highly impact survival and outcomes and need to be addressed when facing an HSCT procedure.
Abstract Background Little is known on the impact of cognitive impairment on instrumental activities of daily living (IADL) in pre-dementia stages of Parkinson's disease (PD). Objective To ...investigate the clinimetric properties, applicability and responsiveness of a brief questionnaire (twelve-item; maximum score = 24) for rating functional abnormalities associated to cognitive impairment in non-demented PD patients (ND-PD). Methods Two studies were carried-out: (1) a clinimetric study validated the Parkinson's Disease-Cognitive Functional Rating Scale (PD-CFRS) against the Older Americans Resource Survey (OARS-IADL) in 53 ND-PD patients and 53 matched controls; (2) A prospective multicenter 6-month responsiveness study involving 120 ND-PD patients explored sensitivity to change. Results In the clinimetric study the PD-CFRS showed intermediate concurrent validity (ICC = 0.50), high test–retest (ICC = 0.82), inter-rater reliability (ICC = 0.80) and internal consistency (Cronbach's α = 0.79), and higher coefficient of variation to detect dysfunction in ND-PD patients (PD-CFRS 86.6% vs. OARS-IADL 8.1%). There was a strong relationship between the PD-CFRS and the global cognitive status determined with the PD-Cognitive Rating Scale ( r = −0.72, p < 0.0001). The responsiveness study recruited 63 patients with normal cognition and 57 with mild cognitive impairment (MCI); an increase of 2 points in the PD-CFRS after 6 months was associated with a clinically significant worsening of the cognitive functional status. According to a discriminant analysis a PD-CFRS cut-off score of ≥3 was found to be optimal for detecting functional impairment in PD-MCI patients. Conclusions Cognitive impairment exerts measurable impact on IADL in ND-PD patients that can be reliable measured with the PD-CFRS, a PD-validated instrument that can be useful in clinical and research settings.
Cortical mean diffusivity (MD) and free water fraction (FW) changes are proposed biomarkers for Alzheimer's disease (AD).
We included healthy control subjects (N = 254), mild cognitive impairment (N ...= 41), and AD dementia (N = 31) patients. Participants underwent a lumbar puncture and a 3 T magnetic resonance imaging. Healthy control subjects were classified following National Institute on Aging-Alzheimer's Association stages (stage 0, N = 220; stage 1, N = 25; and stage 2/3, N = 9). We assessed the cortical MD, cortical FW, and cortical thickness (CTh) changes along the AD continuum.
Microstructural and macrostructural changes show a biphasic trajectory. Stage 1 subjects showed increased CTh and decreased MD and FW with respect the stage 0 subjects. Stage 2/3 subjects showed decreased CTh and increased cortical MD and FW, changes that were more widespread in symptomatic stages.
These results support a biphasic model of changes in AD, which could affect the selection of patients for clinical trials and the use of magnetic resonance imaging as a surrogate marker of disease modification.
The role of innate immunity in dementia with Lewy bodies (DLB) has been little studied. We investigated the levels in cerebrospinal fluid (CSF) of glial proteins YKL-40, soluble TREM2 (sTREM2) and ...progranulin in DLB and their relationship with Alzheimer's disease (AD) biomarkers. We included patients with DLB (n = 37), prodromal DLB (prodDLB, n = 23), AD dementia (n = 50), prodromal AD (prodAD, n = 53), and cognitively normal subjects (CN, n = 44). We measured levels of YKL-40, sTREM2, progranulin, Aβ
, total tau (t-tau) and phosphorylated tau (p-tau) in CSF. We stratified the group DLB according to the ratio t-tau/Aβ
(≥0.52, indicative of AD pathology) and the A/T classification. YKL-40, sTREM2 and progranulin levels did not differ between DLB groups and CN. YKL-40 levels were higher in AD and prodAD compared to CN and to DLB and prodDLB. Patients with DLB with a CSF profile suggestive of AD copathology had higher levels of YKL-40, but not sTREM2 or PGRN, than those without. T+ DLB patients had also higher YKL-40 levels than T-. Of these glial markers, only YKL-40 correlated with t-tau and p-tau in DLB and in prodDLB. In contrast, in prodAD, sTREM2 and PGRN also correlated with t-tau and p-tau. In conclusion, sTREM2 and PGRN are not increased in the CSF of DLB patients. YKL-40 is only increased in DLB patients with an AD biomarker profile, suggesting that the increase is driven by AD-related neurodegeneration. These data suggest a differential glial activation between DLB and AD.
Abstract Introduction We aimed to investigate if cerebral amyloid angiopathy (CAA) is more frequent in genetically determined than in sporadic early-onset forms of Alzheimer's disease (AD) ...(early-onset AD EOAD). Methods Neuroimaging features of CAA, apolipoprotein ( APOE ), and cerebrospinal fluid amyloid β (Aβ) 40 levels were studied in subjects with Down syndrome (DS, n = 117), autosomal-dominant AD (ADAD, n = 29), sporadic EOAD ( n = 42), and healthy controls ( n = 68). Results CAA was present in 31%, 38%, and 12% of cognitively impaired DS, symptomatic ADAD, and sporadic EOAD subjects and in 13% and 4% of cognitively unimpaired DS individuals and healthy controls, respectively. APOE ε4 genotype was borderline significantly associated with CAA in sporadic EOAD ( P = .06) but not with DS or ADAD. There were no differences in Aβ040 levels between groups or between subjects with and without CAA. Discussion CAA is more frequently found in genetically determined AD than in sporadic EOAD. Cerebrospinal fluid Aβ40 levels are not a useful biomarker for CAA in AD.
BACKGROUNDFew prospective studies have attempted to estimate the rate of decline of essential tremor (ET) and these were over a relatively short time period (less than 10 years). We performed a ...long-term study of severity stages in ET using the Glass Scale scoring system. METHODSFifty consecutive patients with severe ET were included. We retrospectively obtained Glass Scale scores throughout the patient's life. Common milestone events were used to help recall changes in tremor severity. RESULTSAccording to the Glass Scale, the age distributions were as follows: score I, 40±17 years, score II, 55±12 years, score III, 64±9 years, and score IV, 69±7 years. A significant negative correlation between age at first symptom and rate of progression was found (r = -0.669, p<0.001). The rate of progression was significantly different (p<0.001) when the first symptom appeared at a younger age (under 40 years of age) compared with older age (40 years or older). DISCUSSIONOur results support the progressive nature of ET. Age at onset was a prognostic factor. The Glass Scale may be a useful tool to determine severity stages during the course of ET in a manner similar to the Hoehn and Yahr Scale for Parkinson's disease.
Episodic memory impairment is the core feature of typical Alzheimer's disease.
To evaluate the performance of two commonly used verbal memory tests to detect mild cognitive impairment due to ...Alzheimer's disease (MCI-AD) and to predict progression to Alzheimer's disease dementia (AD-d).
Prospective study of MCI patients in a tertiary memory disorder unit. Patients underwent an extensive neuropsychological battery including two tests of declarative verbal memory: The Free and Cued Selective Reminding Test (FCSRT) and the word list learning task from the Consortium to Establish a Registry for Alzheimer's disease (CERAD-WL). Cerebrospinal fluid (CSF) was obtained from all patients and MCI-AD was defined by means of the t-Tau/Aβ1-42 ratio. Logistic regression analyses tested whether the combination of FCSRT and CERAD-WL measures significantly improved the prediction of MCI-AD. Progression to AD-d was analyzed in a Cox regression model.
A total of 202 MCI patients with a mean follow-up of 34.2±24.2 months were included and 98 (48.5%) met the criteria for MCI-AD. The combination of FCSRT and CERAD-WL measures improved MCI-AD classification accuracy based on CSF biomarkers. Both tests yielded similar global predictive values (59.9-65.3% and 59.4-62.8% for FCSRT and CERAD-WL, respectively). MCI-AD patients with deficits in both FCSRT and CERAD-WL had a faster progression to AD-d than patients with deficits in only one test.
The combination of FCSRT and CERAD-WL improves the classification of MCI-AD and defines different prognostic profiles. These findings have important implications for clinical practice and the design of clinical trials.
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