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- Bridel, Claire, et al.
(author)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Research review (peer-reviewed)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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- Frisén, Lars, 1939, et al.
(author)
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Posttraumatic seesaw nystagmus abolished by ethanol ingestion.
- 1986
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In: Neurology. - 0028-3878. ; 36:6, s. 841-4
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Journal article (peer-reviewed)abstract
- We describe a patient who was left with a midchiasmal injury and bitemporal hemianopia after head trauma. Four months later, she developed typical seesaw nystagmus and moderate hydrocephalus. Lumbar punctures did not affect the nystagmus, but a temporary cessation was documented after ingestion of ethanol.
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- Lundin, Fredrik, et al.
(author)
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Postural Function in Idiopathic Normal Pressure Hydrocephalus Before and After Shunt Surgery : A Controlled Study Using Computerised Dynamic Posturography (EquiTest)
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Other publication (other academic/artistic)abstract
- Postural dysfunction is one of the major features of idiopathic Normal Hydrocephalus (iNPH). With computerised dynamic posturography (CDP) balance can be assessed objectively. The primary aim of this study was to describe the postural function in iNPH patients pre- and post-operatively in comparison with healthy individuals (HI) using CDP.Subjects and methods: Thirty-five patients (16 M, 19 F) with a mean age of 73 (range 49-81) with iNPH, and sixteen HI (7 M, 9 F) aged 73 (62-89) were included. iNPH patients were operated on with a ventriculo-peritoneal shunt. Patients and HI were tested regarding motor function, balance and cognition. CDP, EquiTest (NeuroCom International, Clackamas, OR), was performed before and three months after shunt surgery and twice in HI, with a three-month interval.Results: Pre-operatively, the 35 patients had poorer balance measured with the Sensory Organising Test (SOT) score in every condition (p= 0.01 in SOT 1 and p<0.001 in SOT 2-6) compared to the HI. The greatest difference was in test conditions measuring mainly vestibular function, where loss of balance (LOB) was frequent. Twenty patients did undergo shunt surgery and 18/20 (90%) were considered shunt responders, with a mean improvement of motor score of 26% (range 5-67 %). There was an improvement post-operatively in the weighted composite SOT score (p<0.05) but no significant change in any of the SOT conditions. LOB was not significantly reduced in any of the test conditions.Conclusion: CDP showed that the patients had a poorer balance than the HI. The greatest difference was in SOT 5-6, indicating that the postural disturbance is of primarily central vestibular origin. There was a slight improvement of balance post-operatively.
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7. |
- Lundin, Fredrik, et al.
(author)
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Pre-Postoperative 1H-MRS-Changes in Frontal Deep White Matter and the Thalamus in Idiopathic Normal Pressure Hydrocephalus
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Other publication (other academic/artistic)abstract
- In a previous study we found a significantly decreased N-acetylaspartate (NAA) and total N-acetyl groups (tNA) in the thalamus in patients with idiopathic normal pressure hydrocephalus (iNPH) compared with healthy individuals (HI). No significant difference between the groups could be found in the frontal deep white matter (FDWM). The primary aim of this study was to investigate if these metabolites in the thalamus were normalised after shunt surgery. The secondary aim was to investigate postoperative metabolic changes in FDWM.Subjects and Methods: Fourteen iNPH-patients, mean age 74 years, and 15 HI, also mean age 74 years, were examined. Assessment of motor scores was performed before and after shunt surgery. Absolute quantitative 1H-MRS (1.5 T, VOI 2.5-3 mL) was performed on the patients in the FDWM and in the thalamus, before and three months after shunt surgery, and also once on the HI. The following metabolites were analysed: tNA, NAA, total creatine (tCr), total choline (tCho), myo-inositol (mIns), glutamate (Glu), and lactate (Lac) concentrations. MRI volumetric calculations of the lateral ventricles were also performed.Results: At three months postoperatively, we found no significant changes of tNA or NAA in the thalamus. In contrast, in FDWM, there was a significant increase of tCho (p=0.01) and a borderline significant decrease of mIns (p=0.06). 12/14 patients were shunt responders (motor function). Median reduction of the lateral ventricle was 16%. A weak correlation between motor score (MOS) and ventricular reduction was observed.Conclusion: Normalisation of thalamic tNA and NAA could not be detected postoperatively. The increased tCho and decreased mIns in the FDWM postoperatively might relate to clinical improvement.
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- Tullberg, Mats, 1965, et al.
(author)
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CSF neurofilament and glial fibrillary acidic protein in normal pressure hydrocephalus.
- 1998
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 50:4, s. 1122-7
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Journal article (peer-reviewed)abstract
- We examined CSF levels of markers of neuronal degeneration and astrogliosis-the light subunit of the neurofilament triplet protein (NFL) and the glial fibrillary acidic protein (GFAP)-in 65 patients with normal pressure hydrocephalus (NPH). NFL was increased sixfold (864 +/- 1,538 [mean +/- SD] versus 156 +/- 81 ng/L; p < or = 0.001) and GFAP twofold (1,116 +/- 1,085 versus 637 +/- 295 ng/L; p < or = 0.01) in NPH patients compared with neurologically healthy age-matched controls. No correlation was found between any particular symptom or sign and GFAP levels in CSF. The levels of NFL, on the other hand, were higher in patients with severe symptoms compared with those with moderate or no symptoms. Furthermore, there was a correlation between a high level of NFL and gait disturbance, incontinence, psychometric incapability, and social dysfunction. A high preoperative NFL level was associated with favorable outcome after shunt surgery. This indicates that NFL is a marker of ongoing and possibly still-reversible axonal damage in NPH.
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