Nevin Manimala

Alzheimers Dement. 2023 Nov 27. doi: 10.1002/alz.13485. Online ahead of print.

ABSTRACT

INTRODUCTION: Protein-based plasma assays provide hope for improving accessibility and specificity of molecular diagnostics to diagnose dementia.

METHODS: Plasma was obtained from participants (N = 837) in our community-based University of Kentucky Alzheimer’s Disease Research Center cohort. We evaluated six Alzheimer’s disease (AD)- and neurodegeneration-related (Aβ40, Aβ42, Aβ42/40, p-tau181, total tau, and NfLight) and five inflammatory biomarkers (TNF𝛼, IL6, IL8, IL10, and GFAP) using the SIMOA-based protein assay platform. Statistics were performed to assess correlations.

RESULTS: Our large cohort reflects previous plasma biomarker findings. Relationships between biomarkers to understand AD-inflammatory biomarker correlations showed significant associations between AD and inflammatory biomarkers suggesting peripheral inflammatory interactions with increasing AD pathology. Biomarker associations parsed out by clinical diagnosis (normal, MCI, and dementia) reveal changes in strength of the correlations across the cognitive continuum.

DISCUSSION: Unique AD-inflammatory biomarker correlations in a community-based cohort reveal a new avenue for utilizing plasma-based biomarkers in the assessment of AD and related dementias.

HIGHLIGHTS: Large community cohorts studying sex, age, and APOE genotype effects on biomarkers are few. It is unknown how biomarker-biomarker associations vary through aging and dementia. Six AD (Aβ40, Aβ42, Aβ42/40, p-tau181, total tau, and NfLight) and five inflammatory biomarkers (TNFα, IL6, IL8, IL10, and GFAP) were used to examine associations between biomarkers. Plasma biomarkers suggesting increasing cerebral AD pathology corresponded to increases in peripheral inflammatory markers, both pro-inflammatory and anti-inflammatory. Strength of correlations, between pairs of classic AD and inflammatory plasma biomarker, changes throughout cognitive progression to dementia.

PMID:38011580 | DOI:10.1002/alz.13485

Med Phys. 2023 Nov 27. doi: 10.1002/mp.16841. Online ahead of print.

ABSTRACT

BACKGROUND: Photon counting detectors (PCDs) for x-ray computed tomography (CT) face spectral distortion from pulse pileup and charge sharing. The photon counting scheme used by many PCDs is threshold-subtract (TS) with pulse height analysis (PHA), where each counter counts up-crossing events when pulses exceed an energy threshold. PCD data are not Poisson-distributed due to charge sharing and pulse pileup, but the counting statistics have never been studied yet.

PURPOSE: The objectives of this study were (1) to propose a modified photon counting scheme, direct energy binning (DB), that is expected to be robust against pulse pileup; (2) to assess the performance of DB compared to TS; and (3) to evaluate its counting statistics.

METHODS: With DB scheme, counter k starts a timer upon an up-crossing event of energy threshold k, and adds a count only if the next higher energy threshold (k+1) was not crossed within a short time window (hence, the pulse peak belongs to the energy bin k). We used Monte Carlo (MC) simulation and assessed count-rate curves and count-rate-dependent spectral imaging task performance for conventional CT imaging as well as water thickness estimation, water-bone material decomposition, and K-edge imaging with tungsten as the K-edge material. We also assessed count-rate-dependent measurement statistics such as expectation, variance, and covariance of total counts as well as energy bin outputs. The agreement with counting statistics models was also evaluated.

RESULTS: The DB scheme improved the count-rate curve, that is, mean measured counts as a function of input count-rate, and peaked with 59% higher count-rate capability than the TS scheme (3.5 × 10⁸ counts per second (cps)/mm² versus 2.3 × 10⁸ cps/mm² ). The Cramér-Rao lower bounds (CRLB) of the variance of basis line integrals estimation for DB was better than those for TS by 2% for the conventional CT imaging, 30% for water-bone material decomposition, and 32% for K-edge imaging at 1000 mA (at 7.3 × 10⁷ cps/sub-pixel after charge sharing). When count-rates were lower, PCD data statistics were dominated by charge sharing: the variance of total counts and lower energy bins was larger than the mean counts; the covariance of bin data was positive and non-zero. When count-rates were higher, PCD data statistics were dominated by pulse pileup: the variance of data was lower than the mean; the covariance of bin data was negative. The transition between the two regimes occurred smoothly, and pulse pileup dominated the statistics ≥400 mA (when the count-rate after charge sharing was 2.9 × 10⁷ cps/sub-pixel and the probability of count-loss for DB was 37%). Both DB and TS had good agreement with Yu-Fessler’s models of total counts; however, DB had a better agreement with Wang’s variance and covariance models for energy bin data than TS did.

CONCLUSIONS: The proposed DB scheme had several advantages over TS. At low to moderate flux, DB could improve the resilience of PCDs to pulse pileup. Counting statistics deviated from the Poisson distribution due to charge sharing for lower count-rate conditions and pulse pileup for higher count-rate conditions.

PMID:38011545 | DOI:10.1002/mp.16841

Curr J Neurol. 2021 Oct 7;20(4):229-234. doi: 10.18502/cjn.v20i4.8349.

ABSTRACT

Background: Atherosclerotic involvement of large and small cerebral arteries leading to infarction is among the most prevalent subtypes of stroke worldwide. The hemodynamic changes due to these arterial pathologies can be studied non-invasively and in real-time by using transcranial Doppler (TCD) techniques. TCD indices of the studied arteries may guide the clinician in differentiating these two underlying arterial pathologies. Methods: A cross-sectional study of patients with small and large vessel types of cerebral infraction based on the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) stroke classification was undertaken in the inpatient population of neurology service of Razi Hospital, Tabriz, Iran, from October 2018 to October 2019. After clinical diagnosis, all cases underwent TCD studies, brain magnetic resonance imaging (MRI), and brain and cervical four-vessel magnetic resonance angiography (MRA). The results of TCD indices related to major arteries of the circle of Willis were tabulated and compared between large and small vessel subtypes of cerebral infarction. Results: A statistically significant difference between right middle cerebral artery (MCA) pulsatility index (PI), left MCA PI, right internal carotid artery (ICA) PI, end-diastolic velocity (EDV), left ICA PI, left ICA EDV, left anterior cerebral artery (ACA) PI, and right vertebral artery (VA) PI measures of the two groups was seen (P < 0.05). In comparison to the large vessel group, left ACA, right VA, and bilateral MCAs and ICAs in the small-vessel stroke group demonstrated an elevated PI. Conclusion: A significant increase of PI occurs in the majority of intracranial arteries of patients with small vessel stroke. This makes PI a valuable marker for differentiating strokes with different underlying pathophysiologies.

PMID:38011485 | PMC:PMC9107575 | DOI:10.18502/cjn.v20i4.8349

Curr J Neurol. 2021 Oct 7;20(4):202-207. doi: 10.18502/cjn.v20i4.8345.

ABSTRACT

Background: One intriguing aspect of stroke is its higher incidence in men as compared to women. Endogenous sex hormones, testosterone and estradiol, may be responsible for this difference. This research aims to study serum testosterone and estradiol levels in men with acute ischemic stroke (AIS) and to correlate these levels with National Institutes of Health Stroke Scale (NIHSS) score and infarct size in computed tomography (CT). Methods: 100 male patients with AIS and 100 age-matched controls were included in this case-control study. Patients with hemorrhagic stroke, taking hormonal preparations, or suffering from chronic illnesses like tuberculosis (TB), cancer, etc. were excluded. Complete history was obtained including presence of established risk factors and physical examination was done in cases and controls with informed written consent. Severity of stroke in cases was assessed by the NIHSS. CT scan of brain was performed within 72 hours of patient’s admission to hospital. The infarct size was measured in centimeters as the largest visible diameter of the infarct on CT scan. Fasting blood samples were obtained for routine investigations and estimating estradiol and testosterone levels. Results: Mean total testosterone level in cases (223.30 ± 143.44 ng/dl) was significantly lower than that of controls (515.34 ± 172.11 ng/dl) (P < 0.001), while estradiol levels had no significant statistical difference (P = 0.260). A significant inverse correlation was found between total testosterone levels and stroke severity (r = -0.581, P < 0.001) and also, total testosterone levels and infarct size (r = -0.557, P < 0.001). Estradiol levels in patients had no significant correlation with stroke severity (P = 0.618) or infarct size (P = 0.463). Conclusion: Low testosterone levels are associated with increased stroke severity and infarct size in men. Further studies are required to establish whether low testosterone is a cause or effect of ischemic stroke and also to explore the potential benefits of testosterone supplementation in men with AIS.

PMID:38011460 | PMC:PMC9107573 | DOI:10.18502/cjn.v20i4.8345

Curr J Neurol. 2020 Jul 5;19(3):146-149. doi: 10.18502/cjn.v19i3.5428.

ABSTRACT

Background: Optic neuritis (ON) is a common visual sign in multiple sclerosis (MS). Although ON is recovered in most cases, other visual functions such as visual perception are affected and are not fully recovered. The aim of this study is to investigate the relationship between visual evoked potential (VEP) P100 and N70 latencies and visual perception using the Developmental Test of Visual Perception-Adolescent and Adult (DTVP-A) in people with MS. Methods: In this cross-sectional study, 24 people with ON due to MS, aged 18-50 years old took part. In order to assess the visual perception and optic nerve conductivity, the DTVP-A and the VEP were accomplished, respectively. Pearson’s product-moment correlation coefficient was used to analyze the data. Results: There was a significant negative correlation between right VEP P100 latency and total score of DTVP-A (r = -0.450, P < 0.05) as well as a significant negative correlation between right VEP P100 latency with visual-motor integration (VMI) subtest of DTVP-A (r = -0.485, P < 0.05). Conclusion: The visual perception has an important role in safety and independent daily activities. Therefore, determining the related factors is essential. Although the findings of the current study revealed a moderate statistical correlation between visual perception and right VEP P100 latency, the small sample size might limit the generalization of our findings; therefore, further study is required to confirm our results.

PMID:38011459 | PMC:PMC8185592 | DOI:10.18502/cjn.v19i3.5428

Curr J Neurol. 2022 Apr 4;21(2):98-104. doi: 10.18502/cjn.v21i2.10493.

ABSTRACT

Background: Swallowing is one of the most complex functions of the central nervous system (CNS), which is controlled by different parts of the brain. Oropharyngeal dysphagia (OD) is one of the most common complications after stroke. Despite a variety of behavioral, compensatory, and rehabilitative methods, many stroke patients still suffer from swallowing disorders that adversely affect their quality of life (QOL). The aim of this study was to evaluate the effect of pyridostigmine on patients with post-stroke dysphagia. Methods: A randomized, double-blind, placebo-controlled clinical trial was carried out on 40 patients suffering from post-stroke dysphagia. Patients were assigned randomly into two groups: intervention and control groups (20 in each group). The intervention group was treated with pyridostigmine (60 mg, three times a day, 30 minutes before each meal for three weeks), and the control group received placebo treatment in the same way. All patients (intervention and control) were evaluated according to National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Functional Communication Measures (FCM)/American Speech-Language-Hearing Association (ASHA) criteria at baseline and after three weeks of intervention. Values of P < 0.05 were considered statistically significant. Results: In the intervention group, the mean values of NIHSS, mRS, and ASHA/FCM were significantly reduced following three weeks of treatment with pyridostigmine (P = 0.002, P = 0.003, and P < 0.001, respectively), but no significant differences were found in the mean NIHSS, mRS, and ASHA/FCM in the placebo group. Conclusion: Although pyridogestamine is somewhat effective in post-stroke dysphagia, it has not been shown to be more important in preventing aspiration pneumonia and length of hospital stay.

PMID:38011458 | PMC:PMC9860206 | DOI:10.18502/cjn.v21i2.10493

Curr J Neurol. 2022 Jan 5;21(1):7-11. doi: 10.18502/cjn.v21i1.9354.

ABSTRACT

Background: Migraine is considered as one of the most common and disabling diseases of the nervous system that has a great impact on quality of life (QOL) and a little risk of neurologic complications such as stroke. Migraine aura is known to be the result of cortical spreading depression and is associated with higher risk of this complication. Thus, the present study was conducted with the aim to compare the effects of topiramate as an antiepileptic, and propranolol in patients with migraine with aura. Methods: The present randomized clinical trial was conducted on patients with migraine with aura referred to the neurology clinic of Golestan Hospital, Ahvaz, Iran, in the period of 2019-2020. The patients were randomized into two groups and received either topiramate or propranolol. The Migraine Disability Assessment Scale (MIDAS) score was evaluated before and at the end of three months after initiating the treatment. Results: Reduction in the MIDAS score in patients taking topiramate (-16.94) was greater than that in the propranolol group (-14.5), but this difference was not statistically significant (P > 0.005). No significant relationship was found between gender and changes in the MIDAS score after the treatment of both groups (P > 0.050). However, the changes in the MIDAS score were greater in younger patients, and this relationship was statistically significant (P < 0.050). Conclusion: There was no significant difference in the efficacy of topiramate and propranolol in patients with migraine with aura. No significant relationship was found between gender and changes in the MIDAS score after the treatment in both groups, but the reduction in the MIDAS scores was significantly higher in younger patients of both groups.

PMID:38011452 | PMC:PMC9527857 | DOI:10.18502/cjn.v21i1.9354

Curr J Neurol. 2021 Oct 7;20(4):222-228. doi: 10.18502/cjn.v20i4.8348.

ABSTRACT

Background: Pediatric-onset multiple sclerosis (POMS) is an autoimmune demyelinating disorder of the central nervous system (CNS), affecting individuals younger than 18 years of age. We sought to characterize the epidemiological and clinical features of patients with POMS in Isfahan, Iran, from April 1997 to March 2020. Methods: The medical records of patients with POMS in the databases of Isfahan Department of Public Health and Isfahan Multiple Sclerosis Society (IMSS) were retrospectively reviewed. The 2006 and 2016 Isfahan Province population censuses were used as reference values for assessing the temporal trend of POMS. Results: From April 1997 to March 2020, 509 individuals under18 years of age were diagnosed with POMS in Isfahan. 404 of these patients (79.4%) were girls, and 105 patients (20.6%) were boys (a female to male ratio of 3.85:1). Most of the patients (83%) were monosymptomatic at onset, with optic neuritis and brainstem-cerebellar disorders being the most frequent initial presentations. Mean ± standard deviation (SD) of age at disease diagnosis was 15.8 ± 2.5 years (ranging from 3 to 18, mode = 18). From April 2019 to March 2020, the crude prevalence and the crude incidence rate of the POMS were 5.42 per 100000 and 1.86 per 100000, respectively. Poisson regression analysis revealed a 3.4% increase in the incidence rate of POMS from April 1997 to March 2020 [relative rate:1.034, 95% confidence interval (CI): 1.021-1.048]. Conclusion: The female to male ratio in our cohort was significantly higher than any other studies conducted previously. The high female to male ratio and increasing incidence of the disease suggest increasing regionalization of care.

PMID:38011448 | PMC:PMC9107569 | DOI:10.18502/cjn.v20i4.8348

Curr J Neurol. 2021 Apr 4;20(2):73-77. doi: 10.18502/cjn.v20i2.6742.

ABSTRACT

Background: Carpal tunnel syndrome (CTS) is the most prevalent entrapment syndrome in the upper limbs, for which pregnancy is a known risk factor. CTS diagnosis is confirmed via nerve conduction studies (NCSs), which sometimes is expensive, and the electrical stimulation makes it an unpleasant diagnostic modality, especially for pregnant subjects. Recently, high-frequency ultrasonography (HF-USG) is known as a diagnostic method. This study is concerned with determining the diagnostic value of this modality for CTS among pregnant women. Methods: This cross-sectional case-control study was conducted with 40 CTS cases and 40 matched controls. The HF-USG of wrists was performed bilaterally on all participants with a focus on the median nerve cross-sectional area (MNCSA) at the carpal tunnel (CT) inlet. Results: Mean MNCSA was statistically different between the CTS group (11.71 ± 1.86 mm², range: 8 to 18 mm²) and the control group (6.75 ± 1.38 mm², range: 4 to 11 mm²) (P < 0.001). The receiver operating characteristic (ROC) curve was drawn, and the cross-sectional area (CSA) cut-off point of 8.5 mm² showed sensitivity and specificity of 98% and 93%, respectively. The positive predictive value (PPV) and the negative predictive value (NPV) were 95% and 98%, respectively, with the mentioned point as the diagnostic threshold. Conclusion: HF-USG of the median nerve can be utilized as a preferable alternative to NCS (the current gold standard diagnostic method) in pregnant women, due to its convenience and lower cost, or at least, it can be used as a screening tool among pregnant women with suspicious symptoms.

PMID:38011444 | PMC:PMC8743181 | DOI:10.18502/cjn.v20i2.6742

Curr J Neurol. 2021 Apr 4;20(2):64-72. doi: 10.18502/cjn.v20i2.6741.

ABSTRACT

Background: Multiple sclerosis (MS) is an inflammatory chronic disease of the central nervous system (CNS) which is related with unpredictable course and increasing disability. Social support as an available interpersonal resource may help patients with MS. The purpose of the present study was to evaluate perceived social support in patients with MS as well as the associated factors. Methods: The sample of this cross-sectional study included 200 patients with MS. Data collection was performed by the completion of the Multidimensional Scale of Perceived Social Support (MSPSS) and a questionnaire which included patients’ characteristics. Results: Patients reported to perceive high support from significant others and their family (median: 24.0 and 23.5, respectively) and less from their friends (median: 20). Moreover, a statistically significant association was found between social support from significant others and marital status (P = 0.010), modification of daily activities (P = 0.018), difficulties with social and family environment (P ≤ 0.001 and P ≤ 0.001, respectively), frequent urination (P = 0.015), and whether they easily forgot (P = 0.049), characterized themselves as anxious (P = 0.049), and believed in God (P = 0.002). Also, a statistically significant association was fond between social support from family and relation with health professionals (P = 0.041), difficulties with social and family environment (P = 0.003 and P ≤ 0.001, respectively), and whether they considered themselves as anxious (P = 0.050), and they believed in God (P ≤ 0.001). Furthermore, a statistically significant association was found between support from friends and modification of daily activities (P = 0.010), help in daily activities (P = 0.016), need for movement assistance (P = 0.001), difficulties with social and family environment (P ≤ 0.001 and P = 0.005, respectively), and whether they considered themselves anxious (P = 0.046). Conclusion: Factors associated with perceived social support should be evaluated when planning holistic care to patients with MS.

PMID:38011438 | PMC:PMC8743177 | DOI:10.18502/cjn.v20i2.6741