Frontiers in Neurology

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ISSN / EISSN : 1664-2295 / 1664-2295
Current Publisher: Frontiers Media SA (10.3389)
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Jennifer M. Ryan, Grace Lavelle, Nicola Theis, , Marika Noorkoiv
Published: 12 May 2021
Frontiers in Neurology, Volume 12; doi:10.3389/fneur.2021.659031

Abstract:
Background: Although the provision of healthcare for people with cerebral palsy (CP) is typically focussed on childhood, many people with CP require access to services periodically throughout their life. Few studies have examined patterns of health service use among young people with CP in England. Understanding patterns of use may inform future service development. Objective: To describe patterns of visits to rehabilitation and medical professionals among ambulatory young people with CP living in England, and identify factors associated with service use. Methods: Sixty-two young people with CP aged 10–19 years [mean (SD) age 13.7 (2.5) years] in Gross Motor Function Classification System (GMFCS) levels I-III reported visits to a range of health professionals, hospital admissions and visits to the emergency department over a median duration of 34 weeks (min–max: 12–34 weeks). Negative binomial models were used to examine factors associated with number of visits. Results: Physiotherapists were the most commonly used professional, with 67.7% of participants visiting a physiotherapist at least once, followed by dentists (66.1%), general practitioners (48.4%), occupational therapists (40.3%) and orthopaedic surgeons (40.3%). Physiotherapists were also the most frequently visited professional with a total of 473 visits (13.3 visits per person-year). Speech and language therapists (5.0 visits per person-year), occupational therapists (4.5 visits per person-year) and nurses (4.3 per person-year) were the next most frequently visited professionals. Age, GMFCS level, and speech impairment were associated with rate of visits to a physiotherapist. Conclusions: The proportion of young people who visited medical and rehabilitation professionals during the study period varied considerably depending on the profession. Generally, the proportion of young people using services was low. In the context of limited resources, data on service use in combination with data on unmet need, may support the reorganisation of services to maximise benefits to young people with CP.
Shan Li, Xiao Sun, Yuanyuan Zhao, Xiang Wang, Xiaokang Ji, ShaoWei Sang, Sai Shao, Yuanyuan Xiang, Guangbin Wang, Ming Lv, et al.
Published: 12 May 2021
Frontiers in Neurology, Volume 12; doi:10.3389/fneur.2021.644963

Abstract:
Metabolic syndrome (MetS) can worsen cerebral arterial atherosclerosis stenosis in patients with stroke; however, its effect on patients without stroke remains ambiguous. This study explored the association of MetS and its individual components with asymptomatic intracranial arterial stenosis (aICAS) and asymptomatic extracranial arterial stenosis (aECAS) among older Chinese adults. A total of 1988 participants from the Kongcun Town study aged ≥40 years and without a history of stroke were enrolled. The baseline data were obtained via face-to-face interviews. MetS was defined according to International Diabetes Federation criteria. Detection of aICAS was conducted using transcranial Doppler ultrasound, followed by diagnosis via magnetic resonance angiography. The evaluation of aECAS was performed using bilateral carotid ultrasonography. The aICAS and aECAS groups were 1:1 matched separately to the non-stenosis group by age and sex. The association between MetS and aICAS or aECAS was analyzed using multivariate logistic regression. Among the 1988 participants, 909 were diagnosed with MetS. The prevalence of MetS was higher in the aICAS group than in the non-stenosis group (P <0.001), but did not differ significantly between the aECAS and non-stenosis groups. The prevalence of aICAS increased with the number of MetS components from 3.4% in the ≤ 1 component group to 12.7% in the ≥4 components group (P for trend <0.001). After adjusting for confounding factors, MetS components associated with aICAS included central obesity, elevated triglyceride levels, and elevated blood pressure. None of the MetS components was associated with aECAS. MetS was positively associated with aICAS, but not with aECAS. Further, different components play different roles in the pathological process leading to aICAS.
Xin-Yao Li, Ying-Mai Yang, Li-Bo Li, Meng-Yu Zhang, Yang-Yu Huang, Jie Wang, Lin Wang, Xin-Hua Wan
Published: 12 May 2021
Frontiers in Neurology, Volume 12; doi:10.3389/fneur.2021.644910

Abstract:
Background: Dopa-responsive dystonia (DRD) is a movement disorder that is highly clinically and genetically heterogeneous. Our study summarizes clinical characteristics and long-term outcomes in patients with dopa-responsive dystonia with the aim of obtaining further knowledge on this disorder. Methods: Patients who met DRD genetic diagnostic criteria through whole-exome sequencing and took levodopa for over 3 years were included in our study. Detailed information was collected on these patients, including family history, age at onset, age and dosage at starting levodopa, current medication and dosage, levodopa duration, diurnal fluctuation, and other clinical features. The Burke–Fahn–Marsden Dystonia Rating Scale-Motor (BFMDRS-M) score was used to evaluate patients' dystonia and variation after levodopa. According to the long-term outcomes, patients were further graded as good (dystonia improved by more than 50% after levodopa, and no further motor symptoms appeared) and poor (dystonia improved by <50% after levodopa, or new motor symptoms appeared). Results: A total of 20 DRD patients were included (11 with GCH1 variants, 9 with TH variants). During long-term levodopa treatment, three patients with TH variants (3/20, 15%) developed motor symptoms, including body jerks and paroxysmal symptoms, and responded well to increasing levodopa doses. The patient with homozygous mutation c.1481C>T/p. Thr494Met harbored more serious symptoms and poor response to levodopa and showed decreased cardiac uptake in MIBG. Conclusions: Most DRD patients showed satisfactory treatment outcomes after long-term levodopa, whereas few patients with TH variants presented motor symptoms, which is considered to be related to dopamine insufficiency. For patients with motor symptoms after long-term levodopa, increasing the dose slowly might be helpful to relieve symptoms.
Ying Zhang, Cimin Dai, Yongcong Shao, Jiaxi Peng, , Yanhong Hou
Published: 12 May 2021
Frontiers in Neurology, Volume 12; doi:10.3389/fneur.2021.641810

Abstract:
Sleep deprivation (SD) induces a negative emotional experience due to a prolonged time spent awake. However, few studies have focused on the mechanism underlying communication within brain networks or alterations during this emotional deterioration. We propose that negative reward judgment is important in poor emotional processing after SD, which will be reflected in functional connectivity in the reward network. We sought to analyze alterations in functional connectivity within the reward network and cerebral cortex. Furthermore, we analyzed changes in functional connectivity correlation with negative emotional experience after SD. Twenty-six healthy volunteers participated in this study. Two resting-state fMRI scans were obtained from the participants, once during resting wakefulness, and once after 36 h of total SD. The bilateral nucleus accumbens (NAc) was selected as a seed region for region of interest (ROI)-to-ROI functional connectivity analysis. Correlation analyses between functional connectivity alterations within the reward network and negative emotional experience were also performed. We found that SD decreased functional connectivity between the left NAc and anterior cingulate cortex (ACC) compared with resting wakefulness. There was a decreased functional connectivity with the ACC and right inferior frontal gyrus (IFG) after SD in the right NAc. Furthermore, decreased functional connectivity between the right NAc and right IFG, and NAc and ACC was negatively correlated with emotional experience scores. Sleep deprivation decreased functional connectivity within the reward network. This may be associated with the enhanced negative emotional experience that was found after total sleep deprivation.
Mariana Alves, Ana Mafalda Abrantes, Gonçalo Portugal, M. Manuela Cruz, Sofia Reimão, Daniel Caldeira, José M. Ferro,
Published: 12 May 2021
Frontiers in Neurology, Volume 12; doi:10.3389/fneur.2021.633900

Abstract:
Background: Previous studies suggested that Parkinson's Disease (PD) patients could have an increased risk of atrial fibrillation. However, data supporting this association is not robust. We aimed to compare the potential risk of atrial fibrillation associated with PD in an age and gender matched case-control study, comparing the p-wave indexes from electrocardiograms and clinical risk scores among groups. Methods: A cross-sectional case-control study was performed. All subjects included in the analysis were clinically evaluated and subjected to a 12-lead electrocardiogram. Two blinded independent raters measured the p-wave duration. Subjects were classified as having normal P-wave duration (<120 ms), partial IAB (P-wave duration ≥ 120 ms, positive in inferior leads), and advanced IAB (p-wave duration ≥ 120 ms with biphasic morphology in inferior leads). Atrial fibrillation risk scores (CHARGE-AF, HATCH, and HAVOC) were calculated. Results: From 194 potential participants, three were excluded from the control group due to a previous diagnosis of atrial fibrillation. Comparing the PD patients (n = 97) with controls (n = 95), there were no statistically significant differences regarding the mean p-wave duration (121 ms vs. 122 ms, p = 0.64) and proportion of advanced interatrial block (OR = 1.4, 95%CI = 0.37–5.80, p = 0.58). All patients had a low or medium risk of developing atrial fibrillation based on the clinical scores. There were no differences between the PD patients and controls regarding the mean values of CHARGE-AF, HATCH, and HAVOC. Conclusions: Our results do not support the hypothesis that PD patients have an increased risk of atrial fibrillation based on the p-wave predictors and atrial fibrillation clinical scores.
, María Pérez-Mato, Manuel Rodríguez-Yáñez, Iria López-Dequidt, José M. Pumar, Tomás Sobrino, Francisco Campos, José Castillo, Andrés da Silva-Candal,
Published: 11 May 2021
Frontiers in Neurology, Volume 12; doi:10.3389/fneur.2021.652867

Abstract:
Aim: The purpose of this study was to investigate clinical and neuroimaging factors associated with stroke recurrence in reperfused ischemic stroke patients, as well as the influence of specific biomarkers of inflammation and endothelial dysfunction. Methods: We conducted a retrospective analysis on a prospectively registered database. Of the 875 patients eligible for this study (53.9% males; mean age 69.6 ± 11.8 years vs. 46.1% females; mean age 74.9 ± 12.6 years), 710 underwent systemic thrombolysis, 87 thrombectomy and in 78, systemic or intra-arterial thrombolysis together with thrombectomy was applied. Plasma levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) were analyzed as markers of inflammation, and soluble tumor necrosis factor-like inducer of apoptosis (sTWEAK) as an endothelial dysfunction marker. The main outcome variables of the study were the presence and severity of leukoaraiosis (LA) and stroke recurrence. Results: The average follow-up time of the study was 25 ± 13 months, during which 127 patients (14.5%) showed stroke recurrence. The presence and severity of LA was more severe in the second stroke episode (Grade III of the Fazekas 28.3 vs. 52.8%; p < 0.0001). IL-6 levels at the first admission and before reperfusion treatment in patients with and without subsequent recurrence were similar (9.9 ± 10.4 vs. 9.1 ± 7.0 pg/mL, p = 0.439), but different for TNFα (14.7 ± 5.6 vs. 15.9 ± 5.7 pg/mL, p = 0.031) and sTWEAK (5,970.8 ± 4,330.4 vs. 8,660.7 ± 5,119.0 pg/mL, p < 0.0001). sTWEAK values ≥7,000 pg/mL determined in the first stroke were independently associated to recurrence (OR 2.79; CI 95%: 1.87–4.16, p < 0.0001). Conclusions: The severity and the progression of LA are the main neuroimaging factors associated with stroke recurrence. Likewise, sTWEAK levels were independently associated to stroke recurrence, so further studies are necessary to investigate sTWEAK as a therapeutic target.
Xiuhe Zhao, , Liang Zhu, M. R. Sandhya Rani, Johnson P. Hampson, Jaison Hampson, Norma J. Hupp, Rup K. Sainju, Daniel Friedman, Maromi Nei, et al.
Published: 11 May 2021
Frontiers in Neurology, Volume 12; doi:10.3389/fneur.2021.669517

Abstract:
Rationale: Currently, there is some ambiguity over the role of postictal generalized electro-encephalographic suppression (PGES) as a biomarker in sudden unexpected death in epilepsy (SUDEP). Visual analysis of PGES, known to be subjective, may account for this. In this study, we set out to perform an analysis of PGES presence and duration using a validated signal processing tool, specifically to examine the association between PGES and seizure features previously reported to be associated with visually analyzed PGES. Methods: This is a prospective, multicenter epilepsy monitoring study of autonomic and breathing biomarkers of SUDEP in adult patients with intractable epilepsy. We studied videoelectroencephalogram (vEEG) recordings of generalized convulsive seizures (GCS) in a cohort of patients in whom respiratory and vEEG recording were carried out during the evaluation in the epilepsy monitoring unit. A validated automated EEG suppression detection tool was used to determine presence and duration of PGES. Results: We studied 148 GCS in 87 patients. PGES occurred in 106/148 (71.6%) seizures in 70/87 (80.5%) of patients. PGES mean duration was 38.7 ± 23.7 (37; 1–169) seconds. Presence of tonic phase during GCS, including decerebration, decortication and hemi-decerebration, were 8.29 (CI 2.6–26.39, p = 0.0003), 7.17 (CI 1.29–39.76, p = 0.02), and 4.77 (CI 1.25–18.20, p = 0.02) times more likely to have PGES, respectively. In addition, presence of decerebration (p = 0.004) and decortication (p = 0.02), older age (p = 0.009), and hypoxemia duration (p = 0.03) were associated with longer PGES durations. Conclusions: In this study, we confirmed observations made with visual analysis, that presence of tonic phase during GCS, longer hypoxemia, and older age are reliably associated with PGES. We found that of the different types of tonic phase posturing, decerebration has the strongest association with PGES, followed by decortication, followed by hemi-decerebration. This suggests that these factors are likely indicative of seizure severity and may or may not be associated with SUDEP. An automated signal processing tool enables objective metrics, and may resolve apparent ambiguities in the role of PGES in SUDEP and seizure severity studies.
Francesco Bruno, Rosa Antonietta Palmiero, Bruno Ferrero, Federica Franchino, Alessia Pellerino, Enrica Milanesi, Riccardo Soffietti, Roberta Rudà
Published: 11 May 2021
Frontiers in Neurology, Volume 12; doi:10.3389/fneur.2021.669493

Abstract:
Introduction: Anti-PD1 agents are widely used in the treatment of solid tumors. This has prompted the recognition of a class of immune-related adverse events (irAEs), due to the activation of autoimmune T-cells. Pembrolizumab is an anti-PD1 agent, which has been related to an increased risk of various neurological irAE (n-irAEs). Here, we present a rare case of pembrolizumab-induced neuropathy of cranial nerves. Case Report: A 72-year-old patient was diagnosed with a lung adenocarcinoma in February 2018 (EGFR–, ALK–, and PDL1 90%). According to the molecular profile, pembrolizumab was started. After three administrations, the patient developed facial paresis, ptosis, ophthalmoplegia, and dysphonia. As brain metastases and paraneoplastic markers were excluded, a drug-related disorder was suspected and pembrolizumab was discontinued. A nerve conduction study and electromyography excluded signs of neuropathy and myopathy at four limbs, and repetitive nerve stimulation was negative. However, altered blink reflex and nerve facial conduction were consistent with an acute neuropathy of the cranial district. Thus, the patient was treated with two cycles of intravenous immunoglobulins (IVIg), which rapidly allowed improvement of both symptoms and neurophysiological parameters. However, the patient died in October 2018 for a progression of lung tumor. Discussion: Only 16 cases of pembrolizumab-related neuropathies have been described so far. Our case is of particular interest for the isolated involvement of cranial nerves and the prompt response to IVIg. Conclusion: N-irAEs are insidious conditions that require solid knowledge of onco-immunotherapy complications: it is mandatory not to delay any treatment that would potentially modify the course of a neurological complication.
Jacek Furtak, Józefina Rakowska, Tadeusz Szylberg, Marek Harat, Bogdan Małkowski, Maciej Harat
Published: 11 May 2021
Frontiers in Neurology, Volume 12; doi:10.3389/fneur.2021.634609

Abstract:
Neuroimaging based on O-[2-(18F)fluoroethyl]-l-tyrosine (FET)-PET provides additional information on tumor grade and extent compared with MRI. Dynamic PET for biopsy target selection further improves results but is often clinically impractical. Static FET-PET performed at two time-points may be a good compromise, but data on this approach are limited. The aim of this study was to compare the histology of lesions obtained from two challenging glioma patients with targets selected based on hybrid dual time-point FET-PET/MRI. Five neuronavigated tumor biopsies were performed in two difficult cases of suspected glioma. Lesions with (T1-CE) and without contrast enhancement (T1 and T2-FLAIR) on MRI were selected. Dual time-point FET-PET imaging was performed 5–15 min (PET10) and 45–60 min (PET60) after radionuclide injection. The most informative FET-PET/MRI images were coregistered with MRI in time of biopsy planning. Five biopsy targets (three from high uptake and two from moderate uptake FET areas) thought to represent the most malignant sites and tumor extent were selected. Histopathological findings were compared with FET-PET and MRI images. Increased FET uptake in the area of non-CE locations on MRI correlated well with high-grade gliomas localized as far as 3 cm from T1-CE foci. Selecting a target in the motor cortex based on FET kinetics defined by dual time-point PET resulted in a grade IV diagnosis after previous negative biopsies based on MRI. An additional grade III diagnosis was obtained from an area of glioma infiltration with moderate FET uptake (between 1 and 1.25 SUV). These findings seem to show that dual time-point FET-PET-based biopsies can provide additional and clinically useful information for glioma diagnosis. Selection of targets based on dual time-point images may be useful for determining the most malignant tumor areas and may therefore be useful for resection and radiotherapy planning.
Weixi Xiong, Lu Lu, Qin Chen, Yingfeng Xiao, Dongmei An, Josemir W. Sander, ,
Published: 11 May 2021
Frontiers in Neurology, Volume 12; doi:10.3389/fneur.2021.663559

Abstract:
Objectives: Reductions in the peripapillary retinal nerve fiber layer (pRNFL) have been reported in epilepsy, namely in drug-resistant people. Hippocampal sclerosis (HS) is the most frequent cause of drug-resistant epilepsy in tertiary care centers. We aimed to evaluate the likelihood and characteristic of RNFL loss in individuals with epilepsy having HS. Methods: Fifty-five adults diagnosed with unilateral HS (mean age of 25 years; 42 female) by magnetic resonance imaging were included in this observational cross-sectional study, 58 age-matched individuals with epilepsy with no detectable structural brain abnormality were included as non-HS, and 55 people without neurological diseases were included as healthy controls. pRNFL of both eyes was measured by optical coherence tomography (OCT). In each individual disease related information was recorded. Results: Among the 55 individuals with unilateral HS, one (1.82%) and ten (18.18%) had significant or borderline abnormal thinning of the pRNFL of the ipsilateral eye to the HS. The average pRNFL ipsilateral to the side of HS was significantly thinner than people with epilepsy non-HS (p = 0.013) and healthy controls (p = 0.000), especially in the inferior quadrants. Only age was significantly correlated with the average and inferior quadrant pRNFL thickness of the ipsilateral eye to the HS (R = −0.286, p = 0.035; R = −0.353, p = 0.008 respectively). Conclusion: These preliminary findings suggest that retinal abnormalities associated with HS may have a specific pattern. Further studies need to confirm this finding and to unravel the underlying mechanism.
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