scholarly journals The Diagnostic and Prognostic Value of Neurofilament Heavy Chain Levels in Immune-Mediated Optic Neuropathies

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Axel Petzold ◽  
Gordon T. Plant

Background. Loss of visual function differs between immune-mediated optic neuropathies and is related to axonal loss in the optic nerve. This study investigated the diagnostic and prognostic value of a biomarker for neurodegeneration, the neurofilament heavy chain (NfH) in three immune-mediated optic neuropathies.Methods. A prospective, longitudinal study including patients with optic neuritis due to multiple sclerosis (MSON,n=20), chronic relapsing inflammatory optic neuritis (CRION,n=19), neuromyelitis optica (NMO,n=9), and healthy controls (n=28). Serum NfH-SMI35 levels were quantified by ELISA.Findings. Serum NfH-SMI35 levels were highest in patients with NMO (mean0.79±1.51 ng/mL) compared to patients with CRION (0.13±0.16 ng/mL,P=0.007), MSON (0.09±0.09,P=0.008), and healthy controls (0.01±0.02 ng/mL,P=0.001). High serum NfH-SMI35 levels were related to poor visual outcome.Conclusions. Blood NfH-SMI35 levels are of moderate diagnostic and more important prognostic value in immune-mediated optic neuropathies. We speculate that longitudinal blood NfH levels may help to identify particular disabling events in relapsing conditions.

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Pamela Freda ◽  
Jeffrey N Bruce ◽  
Carlos Reyes-Vidal ◽  
Yessica De Leon ◽  
Zhezhen Jin ◽  
...  

Abstract Surgical removal of the GH-secreting tumor is the initial treatment of choice for acromegaly. Outcome of surgery is assessed by measuring IGF-1 and glucose-suppressed GH levels. IGF-1 normalization is an essential biochemical criterion for remission. The cut-off for nadir GH after oral glucose that signifies remission, however, is debated. It also remains unclear whether GH levels provide additional prognostic or clinically relevant information when IGF-1 results are definitive. To address this question, we examined how initial postoperative glucose-suppressed GH levels change over time on serial testing in patients who achieve initial remission as defined by IGF-1 normalization. We studied 87 acromegaly patients (48M, 39F) who achieved a normal IGF-1 level after surgery alone longitudinally from 1996 to 2019. All had GH measured before and 60, 90 and 120 minutes after 75 or 100 mg oral glucose (OGTT) at ≥ 3 months after surgery and GH and IGF-1 repeated ≥ 1 year later. GH was by measured by sensitive, 22KDa GH specific assays, either a IRMA (DSL, International Reference Standard (IRS) 88/624) or a chemiluminescence immunoassay (IDS-iSYS, IRS 98/574). OGTT Nadir GH levels were also measured in healthy subjects; n=46 (26 M, 20 F, ages 19-71 yr.) by DSL and n=46 (29 M, 17 F; ages 20-66 yr.) by IDS-iSYS. Nadir GH levels in acromegaly patients were compared to the 95%CI of healthy subjects’ mean and categorized relative to healthy subjects’ 97.5 percentile, which was 0.14 µg/L for both assays. IGF-1 levels were compared to age and gender adjusted normal ranges. Subjects were grouped based on initial nadir GH ≤ or > 0.14 µg/L and the patterns of change in nadir GH and IGF-1 at last follow up or until IGF-1 became elevated (i.e. recurrence). Follow up durations are given as median(range). In follow up, 73 patients remained in remission (normal IGF-1) and 14 had a recurrence (elevated IGF-1). Of the 73 in remission, 55 had initial nadir GH ≤ 0.14 µg/L that persisted to 10 yr.(1-22yr.) of follow up, 5 had initial GH ≤ 0.14 µg/L that rose to > 0.14 µg/L by 9(3-21)yr., 10 had GH > 0.14 µg/L that persisted at 5.5(2-22)yr., and 3 had GH > 0.14 µg/L that fell to ≤ 0.14 µg/L at 5(4-7)yr. of follow up. Of the 14 that recurred, 11 had an initial and persistent GH > 0.14 µg/L and developed an elevated IGF-1 level after 6(1-23) yr.. The 3 other patients that recurred had an initial GH ≤ 0.14 µg/L that rose to > 0.14 µg/L by 1-6 years later and subsequently developed an elevated IGF-1 level by 14-16 years of follow up. In summary, we found that the pattern of normal IGF-1 along with nadir GH > 0.14 µg/L on initial testing or developing with time, was associated with recurrence in 14/32 patients. We also found that initial nadir GH ≤ 0.14 µg/L was highly predictive of long-term persistent remission: 60/63 such patients remained in remission. In conclusion, glucose-suppressed GH levels are of prognostic value in acromegaly patients with normal IGF-1 after surgery.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dan Xu ◽  
Yu Zhang ◽  
Zhi-Yong Zhang ◽  
Xue-Mei Tang

Abstract Objective To analyze the levels of high mobility group box 1 (HMGB1) protein on different courses of juvenile idiopathic arthritis (JIA). Methods In our prospective longitudinal study, children with JIA were included with their blood samples collected at the first visit, 1-month, 3-month, and 6-month follow-up, respectively. Samples were also collected from healthy controls and children with reactive arthritis at the first visit. Levels of HMGB1 were determined using enzyme-linked immunosorbent assays. Clinical disease characteristics and routine laboratory findings were analyzed as well. Results A total of 64 children were enrolled, of whom 31 (48.4%) were female. The median age at the first visit for participants with JIA was 9.25 years (range, 1.42–15.42) and the median duration of disease was 2.38 months (range, 1.53–49.31). Serum HMGB1 levels at the first visit were significantly elevated in children with systemic JIA compared with other groups, and so were in enthesitis-related arthritis versus healthy controls. Significant correlations were established at the first visit between HMGB1 levels and duration of disease, C-reactive protein, percentage of neutrophils, and ferritin. Data from all samples revealed that serum HMGB1 levels in JIA were significantly associated with erythrocyte sedimentation rates, C-reactive protein, percentage of neutrophils, and disease activity scores. Conclusions Serum HMGB1 may be associated with clinical disease activity of JIA and specifically increased at the first visit in children with systemic JIA, suggesting its function as a sensitive inflammatory marker. Further large-scale studies are warranted to explore its spectrum in JIA.


2021 ◽  
Vol 19 ◽  
Author(s):  
Haixia Liu ◽  
Rui Yu ◽  
Yanan Gao ◽  
Xirong Li ◽  
Xiaoni Guan ◽  
...  

: Oxidative stress plays an important role in weight gain induced by antipsychotics in schizophrenia (SCZ). However, little is known about how antioxidant enzymes are involved in weight gain caused by risperidone monotherapy in antipsychotics-naïve first-episode (ANFE) patients with SCZ. Therefore, the main purpose of this study was to investigate the effects of risperidone on several antioxidant enzymes in patients with ANFE SCZ and the relationship between weight gain and changes in antioxidant enzyme activities. The activities of plasma superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as the levels of malondialdehyde (MDA) were measured in 225 ANFE patients and 125 healthy controls. Patients were treated with risperidone monotherapy for 12 weeks. Clinical symptoms, antioxidant enzyme activities and MDA levels were measured at baseline and during follow-up. Compared with healthy controls, the patients showed higher activities of SOD and CAT, but lower MDA levels and GPx activity. At baseline, the CAT activity was associated with bodyweight or BMI. Further, based on a 7% weight increase from baseline to follow-up, we found 75 patients in the weight gain (WG) group and 150 patients in the non-WG group. Comparison between WG group and non-WG group at baseline and during the 12-week follow-up, it was found that after treatment, the SOD activity in the WG group increased while the MDA level decreased in non-WG group. Moreover, baseline SOD and GPx activities were predictors of weight gain at 12-week follow-up. These results suggest that the antioxidant defense system may have predictive value for the weight gain of ANFE SCZ patients after risperidone treatment.


2020 ◽  
Vol 32 (2) ◽  
pp. 92-98
Author(s):  
Miguel Restrepo-Martinez ◽  
Jesus Ramirez-Bermudez ◽  
Leo Bayliss ◽  
Mariana Espinola-Nadurille

AbstractBackground:Encephalitis due to anti-N-methyl-D-aspartate receptor antibodies (ANMDARE) is the most frequent immune-mediated encephalitis. It is distinguished by the subacute onset of neuropsychiatric symptoms.Objective:To evaluate the characteristic neuropsychiatric symptoms and their outcome in patients diagnosed with ANMDARE.Methods:This was a prospective, longitudinal study in patients with a diagnostic suspicion of ANMDARE that presented to the National Institute of Neurology from March 2018 to February 2019. A comparative analysis of two groups (positive N-methyl-D-aspartate receptor [NMDAR] vs. negative NMDAR antibodies in cerebrospinal fluid [CSF]) was done on admission and at discharge. Neuropsychiatric systematic assessments included the Neuropsychiatric Inventory Questionnaire, the Bush Francis Catatonia Rating Scale, the Confusion Assessment Method Severity, the Montreal Cognitive Assessment, and the Overt Agitation Severity Scale.Results:24 individuals were analysed: 14 had positive NMDAR antibodies, and 10 had negative NMDAR antibodies in CSF. On admission, agitation/aggression, euphoria/exaltation, and disinhibition were more common in patients with positive antibodies. Excited catatonia and delirium were diagnosed more frequently in patients with positive antibodies. At discharge, there was an important decrease in neuropsychiatric symptoms, but substantial cognitive impairment remained. The mean hospitalisation length was 41.71 (SD 39.33) days for patients with definitive ANMDARE (p 0.259).Conclusions:Neuropsychiatric symptoms profile in ANMDARE was associated with the early onset of euphoria/exaltation and disinhibition, accompanied by marked psychomotor agitation. When ANMDARE was suspected, the presence of excited-type catatonia and delirium showed a tendency to predict definitive ANMDARE. At discharged, most patients recovered from catatonia, delirium, and psychosis, but marked cognitive symptoms, anxiety, and depression persisted at discharge.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013067
Author(s):  
David Fischer ◽  
Samuel B Snider ◽  
Megan E Barra ◽  
William R Sanders ◽  
Otto Rapalino ◽  
...  

Background and Objectives:In patients with severe coronavirus disease 2019 (COVID-19), disorders of consciousness (COVID-DoC) have emerged as a serious complication. The prognosis and pathophysiology of COVID-DoC remain unclear, complicating decisions about continuing life-sustaining treatment. We describe the natural history of COVID-DoC and investigate its associated brain connectivity profile.Methods:In a prospective, longitudinal study, we screened consecutive patients with COVID-19 at our institution. We enrolled critically ill adult patients with a DoC unexplained by sedation or structural brain injury, and who were planned to undergo a brain MRI. We performed resting state functional MRI and diffusion MRI to evaluate functional and structural connectivity, as compared to healthy controls and patients with DoC resulting from severe traumatic brain injury (TBI). We assessed the recovery of consciousness (command-following) and functional outcomes (Glasgow Outcome Scale Extended [GOSE] and the Disability Rating Scale [DRS]) at hospital discharge, three months post-discharge, and six months post-discharge. We also explored whether clinical variables were associated with recovery from COVID-DoC.Results:After screening 1,105 patients with COVID-19, we enrolled twelve with COVID-DoC. The median age was 63.5 years [interquartile range 55-76.3]. Excluding one who died shortly after enrollment, all of the remaining eleven patients recovered consciousness, after 0-25 days (median 7 [5-14.5]) following the cessation of continuous intravenous sedation. At discharge, all surviving patients remained dependent – median GOSE 3 [1-3], median DRS 23 [16-30]. However ultimately, except for two patients with severe polyneuropathy, all returned home with normal cognition and minimal disability – at three months, median GOSE 3 [3-3], median DRS 7 [5-13]; at six months, median GOSE 4 [4-5], median DRS 3 [3-5]. Ten patients with COVID-DoC underwent advanced neuroimaging; functional and structural brain connectivity in COVID-DoC was diminished compared to healthy controls, and structural connectivity was comparable to patients with severe TBI.Discussion:Patients who survived invariably recovered consciousness after COVID-DoC. Though disability was common following hospitalization, functional status improved over the ensuing months. While future research is necessary, these prospective findings inform the prognosis and pathophysiology of COVID-DoC.Trial Registration Information:Clinicaltrials.gov, NCT04476589, submitted 7/2020, first enrolled 7/20/2020, https://clinicaltrials.gov/ct2/show/NCT04476589


2020 ◽  
Vol 91 (9) ◽  
pp. 960-967 ◽  
Author(s):  
Alberto Benussi ◽  
Thomas K Karikari ◽  
Nicholas Ashton ◽  
Stefano Gazzina ◽  
Enrico Premi ◽  
...  

ObjectiveTo assess the diagnostic and prognostic value of serum neurofilament light (NfL) and serum phospho-Tau181 (p-Tau181) in a large cohort of patients with frontotemporal lobar degeneration (FTLD).MethodsIn this retrospective study, performed on 417 participants, we analysed serum NfL and p-Tau181 concentrations with an ultrasensitive single molecule array (Simoa) approach. We assessed the diagnostic values of serum biomarkers in the differential diagnosis between FTLD, Alzheimer’s disease (AD) and healthy ageing; their role as markers of disease severity assessing the correlation with clinical variables, cross-sectional brain imaging and neurophysiological data; their role as prognostic markers, considering their ability to predict survival probability in FTLD.ResultsWe observed significantly higher levels of serum NfL in patients with FTLD syndromes, compared with healthy controls, and lower levels of p-Tau181 compared with patients with AD. Serum NfL concentrations showed a high accuracy in discriminating between FTLD and healthy controls (area under the curve (AUC): 0.86, p<0.001), while serum p-Tau181 showed high accuracy in differentiating FTLD from patients with AD (AUC: 0.93, p<0.001). In FTLD, serum NfL levels correlated with measures of cognitive function, disease severity and behavioural disturbances and were associated with frontotemporal atrophy and indirect measures of GABAergic deficit. Moreover, serum NfL concentrations were identified as the best predictors of survival probability.ConclusionsThe assessment of serum NfL and p-Tau181 may provide a comprehensive view of FTLD, aiding in the differential diagnosis, in staging disease severity and in defining survival probability.


Cephalalgia ◽  
2018 ◽  
Vol 39 (6) ◽  
pp. 722-731 ◽  
Author(s):  
Todd J Schwedt ◽  
Jacob Peplinski ◽  
Pamela Garcia-Filion ◽  
Visar Berisha

Background and Objective Some individuals with migraine report the presence of speech changes during their migraine attacks. The goal of this study was to compare objective features of speech during the migraine pre-attack, the migraine attack, and during the interictal period. Methods This was a prospective, longitudinal, observational study of adults with episodic migraine and healthy non-migraine controls. Participants provided speech samples three times per day using a speech elicitation tool included within a mobile app. Six complementary speech features that capture articulation and prosody were extracted from speech samples. Participants with migraine maintained a daily headache diary using the same app. A mixed effects model and t-tests were used to investigate differences in speech features between controls, the migraine pre-attack phase, the migraine attack, and the interictal period. Results In total, 56,767 speech samples were collected, including 43,102 from 15 individuals with migraine and 13,665 from matched healthy controls. Significant group-level differences in speech features were identified between those with migraine and healthy controls and within the migraine group during the pre-attack vs. attack vs. interictal periods (all p < .05). Most consistently, speech changes occurred in the speaking rate, articulation rate and precision, and phonatory duration. Within-subject analysis revealed that seven of 15 individuals with migraine showed significant change in at least one speech feature when comparing the migraine attack vs. interictal phase and four showed similar changes when comparing the pre-attack vs. interictal phases. Conclusions Changes in speech occurred in almost half of the individuals during migraine attacks. Once confirmed in subsequent studies, speech changes could be considered a feature of the migraine attack.


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