| 1. |
- Dobson, Hannah, et al.
(författare)
-
Elevated plasma neurofilament light and glial fibrillary acidic protein in epilepsy versus nonepileptic seizures and nonepileptic disorders
- 2024
-
Ingår i: EPILEPSIA. - 0013-9580 .- 1528-1167.
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveResearch suggests that recurrent seizures may lead to neuronal injury. Neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAP) levels increase in cerebrospinal fluid and blood in response to neuroaxonal damage, and they have been hypothesized as potential biomarkers for epilepsy. We examined plasma NfL and GFAP levels and their diagnostic utility in differentiating patients with epilepsy from those with psychogenic nonepileptic seizures (PNES) and other nonepileptic disorders.MethodsWe recruited consecutive adults admitted for video-electroencephalographic monitoring and formal neuropsychiatric assessment. NfL and GFAP levels were quantified and compared between different patient groups and an age-matched reference cohort (n = 1926) and correlated with clinical variables in patients with epilepsy.ResultsA total of 138 patients were included, of whom 104 were diagnosed with epilepsy, 22 with PNES, and 12 with other conditions. Plasma NfL and GFAP levels were elevated in patients with epilepsy compared to PNES, adjusted for age and sex (NfL p = .04, GFAP p = .04). A high proportion of patients with epilepsy (20%) had NfL levels above the 95th age-matched percentile compared to the reference cohort (5%). NfL levels above the 95th percentile of the reference cohort had a 95% positive predictive value for epilepsy. Patients with epilepsy who had NfL levels above the 95th percentile were younger than those with lower levels (37.5 vs. 43.8 years, p = .03).SignificanceAn elevated NfL or GFAP level in an individual patient may support an underlying epilepsy diagnosis, particularly in younger adults, and cautions against a diagnosis of PNES alone. Further examination of the association between NfL and GFAP levels and specific epilepsy subtypes or seizure characteristics may provide valuable insights into disease heterogeneity and contribute to the refinement of diagnosis, understanding pathophysiological mechanisms, and formulating treatment approaches.
|
|
| 2. |
- Eratne, Dhamidhu, et al.
(författare)
-
Plasma neurofilament light chain is increased in Niemann-Pick Type C but glial fibrillary acidic protein remains normal
- 2024
-
Ingår i: Acta Neuropsychiatrica. - 0924-2708 .- 1601-5215. ; , s. 1-6
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Niemann-Pick Type C (NPC) is a genetic neurodegenerative lysosomal storage disorder commonly associated with psychiatric symptoms and delays to accurate diagnosis and treatment. This study investigated biomarker levels and diagnostic utility of plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in NPC compared to healthy controls. METHODS: Patients with NPC were recruited from a specialist assessment and management service. Data was available from an age and sex-matched healthy control group. NfL and GFAP were measured on Quanterix Simoa HD-X analysers and groups compared using generalised linear models. NfL levels were compared to, and percentiles derived from, recently developed NfL reference ranges. RESULTS: Plasma NfL was significantly elevated in 11 patients with NPC compared to 25 controls (mean 17.1pg/mL vs 7.4pg/mL, p<0.001), and reference ranges (all >98th percentile). NfL distinguished NPC from controls with high accuracy. GFAP levels were not elevated in NPC (66.6pg/mL vs 75.1pg/mL). DISCUSSION: The study adds important evidence on the potential diagnostic utility of plasma NfL in NPC, extends the literature of NfL as a diagnostic tool to differentiate neurodegenerative from primary psychiatric disorders, and adds support to the pathology in NPC primarily involving neuronal, particularly axonal, degeneration.
|
|
| 3. |
- Jakabek, David, et al.
(författare)
-
Regional structural hypo- and hyperconnectivity of frontal–striatal and frontal–thalamic pathways in behavioral variant frontotemporal dementia
- 2018
-
Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471. ; 39:10, s. 4083-4093
-
Tidskriftsartikel (refereegranskat)abstract
- Behavioral variant frontotemporal dementia (bvFTD) has been predominantly considered as a frontotemporal cortical disease, with limited direct investigation of frontal–subcortical connections. We aim to characterize the grey and white matter components of frontal–thalamic and frontal–striatal circuits in bvFTD. Twenty-four patients with bvFTD and 24 healthy controls underwent morphological and diffusion imaging. Subcortical structures were manually segmented according to published protocols. Probabilistic pathways were reconstructed separately from the dorsolateral, orbitofrontal and medial prefrontal cortex to the striatum and thalamus. Patients with bvFTD had smaller cortical and subcortical volumes, lower fractional anisotropy, and higher mean diffusivity metrics, which is consistent with disruptions in frontal–striatal–thalamic pathways. Unexpectedly, regional volumes of the striatum and thalamus connected to the medial prefrontal cortex were significantly larger in bvFTD (by 135% in the striatum, p =.032, and 217% in the thalamus, p =.004), despite smaller dorsolateral prefrontal cortex connected regional volumes (by 67% in the striatum, p =.002, and 65% in the thalamus, p =.020), and inconsistent changes in orbitofrontal cortex connected regions. These unanticipated findings may represent compensatory or maladaptive remodeling in bvFTD networks. Comparisons are made to other neuropsychiatric disorders suggesting a common mechanism of changes in frontal–subcortical networks; however, longitudinal studies are necessary to test this hypothesis.
|
|
| 4. |
- Jakabek, David, et al.
(författare)
-
Structural and microstructural thalamocortical network disruption in sporadic behavioural variant frontotemporal dementia
- 2023
-
Ingår i: NeuroImage: Clinical. - 2213-1582. ; 39, s. 1-11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Using multi-block methods we combined multimodal neuroimaging metrics of thalamic morphology, thalamic white matter tract diffusion metrics, and cortical thickness to examine changes in behavioural variant frontotemporal dementia. (bvFTD). Method: Twenty-three patients with sporadic bvFTD and 24 healthy controls underwent structural and diffusion MRI scans. Clinical severity was assessed using the Clinical Dementia Rating scale and behavioural severity using the Frontal Behaviour Inventory by patient caregivers. Thalamic volumes were manually segmented. Anterior and posterior thalamic radiation fractional anisotropy and mean diffusivity were extracted using Tract-Based Spatial Statistics. Finally, cortical thickness was assessed using Freesurfer. We used shape analyses, diffusion measures, and cortical thickness as features in sparse multi-block partial least squares (PLS) discriminatory analyses to classify participants within bvFTD or healthy control groups. Sparsity was tuned with five-fold cross-validation repeated 10 times. Final model fit was assessed using permutation testing. Additionally, sparse multi-block PLS was used to examine associations between imaging features and measures of dementia severity. Results: Bilateral anterior-dorsal thalamic atrophy, reduction in mean diffusivity of thalamic projections, and frontotemporal cortical thinning, were the main features predicting bvFTD group membership. The model had a sensitivity of 96%, specificity of 68%, and was statistically significant using permutation testing (p = 0.012). For measures of dementia severity, we found similar involvement of regional thalamic and cortical areas as in discrimination analyses, although more extensive thalamo-cortical white matter metric changes. Conclusions: Using multimodal neuroimaging, we demonstrate combined structural network dysfunction of anterior cortical regions, cortical-thalamic projections, and anterior thalamic regions in sporadic bvFTD.
|
|
| 5. |
- Kang, Matthew J.Y., et al.
(författare)
-
Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders
- 2024
-
Ingår i: Acta Neuropsychiatrica. - 0924-2708 .- 1601-5215. ; 36:1, s. 17-28
-
Tidskriftsartikel (refereegranskat)abstract
- Objective People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown. Methods We collected longitudinal diagnostic information (mean=36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other), and PSY. We pre-specified NfL>582pg/mL as indicative of ND/MCI/other. Results Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone. Conclusions CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.
|
|
| 6. |
- Kang, Matthew J.Y., et al.
(författare)
-
Plasma neurofilament light chain is not elevated in people with first-episode psychosis or those at ultra-high risk for psychosis
- 2024
-
Ingår i: Schizophrenia Research. - 0920-9964. ; 267, s. 269-272
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Neurofilament light chain (NfL), a blood biomarker of neuronal injury, shows promise in distinguishing neurodegenerative disorders from psychiatric conditions. This is especially relevant in psychosis, given neurological conditions such as autoimmune encephalitis and Niemann Pick Type C disease (NPC) may initially present with psychotic symptoms. Whilst NfL levels have been studied in established schizophrenia cases, their levels in first-episode psychosis (FEP) and ultra-high risk (UHR) for psychosis individuals remain largely unexplored. This study aimed to compare plasma NfL in people with FEP or UHR with healthy controls, as well as explore its associations with clinical data. Method: We retrospectively analysed plasma NfL in 63 participants, consisting of 29 individuals with FEP, 10 individuals with UHR, and 24 healthy controls. We used general linear models (GLM), which were bootstrapped, to compute bias-corrected and accelerated (BCa) 95 % confidence intervals (CIs). Results: Mean NfL levels were 5.2 pg/mL in FEP, 4.9 pg/mL in UHR, and 5.9 pg/mL in healthy controls. Compared to healthy controls, there were no significant differences in NfL levels in the FEP group (β = −0.22, 95 % CI [−0.86, 0.39], p = 0.516) nor UHR group (β = −0.37, 95 % CI [−0.90, 0.19], p = 0.182). There were no significant associations between NfL levels and clinical variables in the FEP group. Discussion: Our study is the first to demonstrate that plasma NfL levels are not significantly elevated in individuals at UHR for psychosis compared to healthy controls, a finding also observed in the FEP cohort. These findings bolster the potential diagnostic utility of NfL in differentiating between psychiatric and neurodegenerative disorders.
|
|
| 7. |
- Power, Brian D., et al.
(författare)
-
Morphometric analysis of thalamic volume in progressive supranuclear palsy : In vivo evidence of regionally specific bilateral thalamic atrophy
- 2017
-
Ingår i: Psychiatry Research - Neuroimaging. - : Elsevier BV. - 0925-4927. ; 265, s. 65-71
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated whether differences were detectable in the volume and shape of the dorsal thalamus on magnetic resonance imaging in patients with progressive supranuclear palsy (PSP). Manual segmentation of the left and right thalami on magnetic resonance imaging scans occurred in 22 patients with clinically diagnosed PSP and 23 healthy controls; thalamic volumes (left, right, total) were calculated. Between group differences were explored by multivariate analysis of co-variance, using age and intracranial volume as covariates. Analysis of the shape of the thalamus was performed using the spherical harmonic point distribution method software package. Patients with PSP were found to have significant bilateral thalamic atrophy on magnetic resonance imaging; there was significant shape deflation over the anterior-lateral and anterior-ventral surfaces bilaterally, and over the right caudal thalamus. Recognizing decreased thalamic morphology in PSP patients in vivo may be an important component of an ensemble of diagnostic biomarkers in the future, particularly given the difficulty of distinguishing PSP from other Parkinsonian conditions early in the disease course.
|
|
| 8. |
- Wannan, Cassandra M.J., et al.
(författare)
-
Plasma neurofilament light protein is differentially associated with age in individuals with treatment-resistant schizophrenia and bipolar affective disorder compared to controls
- 2024
-
Ingår i: Psychiatry Research. - 0165-1781. ; 339
-
Tidskriftsartikel (refereegranskat)abstract
- Accelerated brain ageing has been observed in multiple psychiatric disorders. This study examined whether relationships between age and plasma neurofilament light (NfL) protein differed in individuals with psychiatric disorders (major depressive disorder (n = 42), bipolar affective disorder (n = 121), treatment-resistant schizophrenia (TRS, n = 82)) compared to two healthy control (HC) groups (n = 1,926 and n = 59). Compared to two independent HC samples, individuals with TRS demonstrated a stronger positive relationship between age and NfL levels. Individuals with BPAD had a stronger negative relationship between age and NfL levels compared to the large normative HC cohort, but not locally-acquired HCs. These findings show that plasma NfL levels are differentially associated with age in individuals with TRS and BPAD compared to healthy individuals.
|
|
