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Axel Petzold

Publications and source records attributed to Axel Petzold.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of two ELISA methods for measuring levels of the phosphorylated neurofilament heavy chain.

BACKGROUND: Recent studies suggest that the quantification of neurofilament subunits in cerebrospinal fluid (CSF), blood and amniotic fluid may reflect neuroaxonal damage and be of high clinical value. The present study aims to cross-validate two different independently developed ELISA techniques for the quantification of the phosphorylated axonal forms of the neurofilament heavy chain (pNfH). METHODS: The London ELISA method is based on barbitone buffer and the commercially available SMI35 capture antibody. The Gainesville method uses Tris-buffered saline (TBS) and an affinity purified chicken polyclonal capture antibody (C-pNfH). Coded CSF from 50 patients with neurological diseases were analyzed in duplicate by both laboratories, each using both ELISA methods, but with each lab using their own detection antibody, tertiary antibody and chromogen. Methods were compared using Bland-Altman plots. Correlation and regression analyses were used to allow for transformation of values between both methods. RESULTS: The Bland-Altman plots demonstrated that 96% of all samples fell into the narrow 95% limits of agreement (0.04 units of OD). There was a high correlation (Spearman R=0.92, p<0.0001 and Pearson R=0.98, p<0.0001) between the Gainesville (Y) and the London (X) method with Y=0.132+1.104(*)X. The previously determined upper reference limit of 0.73 mg/l (London method) corresponds to 0.94 mg/l for the Gainesville method. CSF pNfH levels above the reference limit were observed in patients with encephalitis, encephalomyelitis, hydrocephalus, subarachnoid haemorrhage, spino-muscular atrophy, stroke and cancer with both methods agreeing in all cases. CONCLUSION: The two assays are in excellent agreement, suggesting that pNfH, which has a number of unusual protein chemical features, may be the biomarker of choice for the routine and robust detection of axonal injury and degeneration in both research and clinical contexts.

Adolescent↗
PubMed2006

The neurofilament heavy chain (NfH) in the cerebrospinal fluid diagnosis of Alzheimer's disease.

BACKGROUND/AIMS: Attempting to improve the cerebrospinal fluid (CSF) diagnosis of Alzheimer's disease (AD), the neurofilament heavy chain isoform, NfH(SMI35) was compared to other CSF markers [total tau, phospho-tau, amyloid beta 1-42 (Abeta42), the ratio of amyloid beta fragments Abeta42/Abeta40 (Abeta ratio)]. METHODS: CSF levels were determined in patients with AD (n = 109), mild cognitive impairment (MCI, n = 25), frontotemporal dementia (n = 15), vascular dementia (VD, n = 41), and controls (n = 58). RESULTS: CSF NfH(SMI35) was elevated in AD and VD as compared to controls (p < 0.05). Total tau was higher in AD as compared to controls (p < 0.05). CSF phospho-tau was elevated in AD as compared to controls and VD (p < 0.05 each). CSF Abeta42 and Abeta ratios in AD were lower than in MCI and controls (p < 0.05 each). CONCLUSION: The diagnostic potential of NfH(SMI35) is not superior to that of other CSF markers.

Adult↗
PubMed2006

Measurement of high affinity antibodies on antigen-immunoblots.

We describe a semi-quantitative method for measuring the relative affinity of antigen-specific oligoclonal IgG bands separated by isoelectric focusing followed by blotting onto antigen-coated membrane and incubation with sodium thiocyanate. When the developed blot is digitised in greyscale, densitograms can be made and peak areas calculated using ImageJ freeware. By expressing peak area as a percentage of the total area under the curve we have shown that there is a statistically significant rise in percentage of peak area for a given band which persists with increasing molarities of sodium thiocyanate.

Area Under Curve↗
PubMed2006

Neurofilament heavy-chain NfH(SMI35) in cerebrospinal fluid supports the differential diagnosis of Parkinsonian syndromes.

We aimed to evaluate the potential of the cerebrospinal fluid (CSF) axonal damage biomarker NfH(SMI35) in the laboratory-supported differential diagnosis of parkinsonian syndromes. Patients with idiopathic Parkinson's disease (PD; n = 22), multiple-system atrophy (MSA; n = 21), progressive supranuclear palsy (PSP; n = 21), corticobasal degeneration (CBD; n = 6), and age-matched controls (n = 45) were included. CSF levels of NfH(SMI35) were measured using ELISA. Levels of CSF NfH(SMI35) were elevated in PSP compared to PD and controls (P < 0.05 each). They were also significantly higher in MSA than in PD and controls (P < 0.05 each). NfH(SMI35) differentiated PD from PSP with a sensitivity of 76.5% and a specificity of 94.4%. Axonal damage as measured by CSF NfH(SMI35) is most prominent in the more rapidly progressive syndromes PSP and MSA as compared to PD or CBD. CSF NfH(SMI35) may therefore be of some value for the laboratory-supported differential diagnosis of atypical parkinsonian syndromes.

Adult↗
PubMed2006

Early identification of secondary brain damage in subarachnoid hemorrhage: a role for glial fibrillary acidic protein.

Secondary ischaemic deficit adversely affects outcome in patients with subarachnoid hemorrhage (SAH). Astrocytes are vulnerable to ischemia, releasing glial fibrillary acidic protein (GFAP) when challenged. In this study, we followed nine patients with SAH who underwent extra-ventricular drainage for the management of secondary hydrocephalus. Cerebrospinal fluid (CSF) was collected daily for up to 14 days. CSF GFAP was quantified using a standard ELISA. In the patients, we found that the CSF GFAP values were pathologically elevated in 83/89 (93%) of the CSF samples. The levels were highest on day 1 (median = 47.64 ng/mL) and decreased to 11.19 ng/mL on day 3, leveling out at approximately 1 ng/mL after 10 days. In non-survivors, a secondary rise of GFAP levels became significant during the high-risk period for vasospasm, with median levels of 21.76 ng/mL compared to 2.62 ng/mL in the survivors (p = 0.037) on day 6. This study suggests that CSF GFAP levels are of prognostic value in SAH. Additionally, the difference in the slope of GFAP levels between survivors (rapid wash-out) and non-survivors (secondary peaks) may allow difierentiation between primary brain injury from secondary brain damage due to delayed cerebral ischaemia.

Aged↗
PubMed2006

Clinical disorders affecting mesopic vision.

Vision in the mesopic range is affected by a number of inherited and acquired clinical disorders. We review these conditions and summarize the historical background, describing the clinical characteristics alongside the genetic basis and molecular biological mechanisms giving rise to rod and cone dysfunction relevant to twilight vision. The current diagnostic gold standards for each disease are discussed and curative and symptomatic treatment strategies are summarized.

Electroretinography↗
PubMed2006

Spectrophotometry for cerebrospinal fluid pigment analysis.

The use of spectrophotometry for the analysis of the cerebrospinal fluid (CSF) is reviewed. The clinically relevant CSF pigments--oxyhemoglobin and bilirubin--are introduced and discussed with regard to clinical differential diagnosis and potentially confounding variables (the four T's: traumatic tap, timing, total protein, and total bilirubin). The practical laboratory aspects of spectrophotometry and automated techniques are presented in the context of analytical and clinical specificity and sensitivity. The perceptual limitations of human color vision are highlighted and the use of visual assessment of the CSF is discouraged in light of recent evidence from a national audit in the United Kingdom. Finally, future perspectives including the need for longitudinal CSF profiling and routine spectrophotometric calibration are outlined.

Bilirubin↗
PubMed2005

Extracellular N-acetylaspartate depletion in traumatic brain injury.

N-Acetylaspartate (NAA) is almost exclusively localized in neurons in the adult brain and is present in high concentration in the CNS. It can be measured by proton magnetic resonance spectroscopy and is seen as a marker of neuronal damage and death. NMR spectroscopy and animal models have shown NAA depletion to occur in various types of chronic and acute brain injury. We investigated 19 patients with traumatic brain injury (TBI). Microdialysis was utilized to recover NAA, lactate, pyruvate, glycerol and glutamate, at 12-h intervals. These markers were correlated with survival and a 6-month Glasgow Outcome Score. Eleven patients died and eight survived. A linear mixed model analysis showed a significant effect of outcome and of the interaction between time of injury and outcome on NAA levels (p = 0.009 and p = 0.004, respectively). Overall, extracellular NAA was 34% lower in non-survivors. A significant non-recoverable fall was observed in this group from day 4 onwards, with a concomitant rise in lactate-pyruvate ratio and glycerol. These results suggest that mitochondrial dysfunction is a significant contributor to poor outcome following TBI and propose extracellular NAA as a potential marker for monitoring interventions aimed at preserving mitochondrial function.

Adult↗
PubMed2005

Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss.

This review on the role of neurofilaments as surrogate markers for axonal degeneration in neurological diseases provides a brief background to protein synthesis, assembly, function and degeneration. Methodological techniques for quantification are described and a protein nomenclature is proposed. The relevance for recognising anti-neurofilament autoantibodies is noted. Pathological implications are discussed in view of immunocytochemical, cell-culture and genetic findings. With reference to the present symposium on multiple sclerosis, the current literature on body fluid levels of neurofilaments in demyelinating disease is summarised.

Animals↗
PubMed2005

Why human color vision cannot reliably detect cerebrospinal fluid xanthochromia.

BACKGROUND: Visual assessment of cerebrospinal fluid (CSF) for xanthochromia (yellow color) is practiced by the majority of laboratories worldwide as a means of diagnosing intracranical bleeds. METHODS: Colorimetric and spectrophotometric analysis of CSF samples for recognizing the presence of bilirubin either in low concentrations or in the presence of hemolysed blood. RESULTS: The experiments provide the physiological and colorimetric basis for abandoning visual assessment of CSF for xanthochromia. CONCLUSIONS: We strongly recommend relying on spectrophotometry as the analytical method of choice.

Bilirubin↗
PubMed2004

Serum S100B in primary progressive multiple sclerosis patients treated with interferon-beta-1a.

S100B belongs to a family of calcium-binding proteins implicated in intracellular and extracellular regulatory activities. This study of serum S100B in primary progressive multiple sclerosis (PPMS) is based on data obtained from a randomized, controlled trial of Interferon beta-1a in subjects with PPMS. The key questions were whether S100B levels were associated with either disability or MRI findings in primary progressive MS and whether Interferon beta-1a has an effect on their S100B levels. Serial serum S100B levels were measured using an ELISA method. The results demonstrated that serum S100B is not related to either disease progression or MRI findings in subjects with primary progressive MS given Interferon beta-1a. Furthermore there is no correlation between S100B levels and the primary and secondary outcome measures.

Adult↗
PubMed2004

Cerebrospinal fluid nitrite/nitrate correlated with oxyhemoglobin and outcome in patients with subarachnoid hemorrhage.

The findings of various studies reporting temporal changes in CSF total nitrite/nitrate (NOx) levels after subarachnoid hemorrhage (SAH) vary considerably. The study group comprised 10 patients with SAH and 10 control subjects. Total nitrite/nitrate concentration was measured by a vanadium-based assay with the colorimetric Griess reaction. CSF oxyhemoglobin level was assessed by spectrophotometry. After an initial peak (22.6+/-10.1 microM) within first 24 h after SAH, CSF NOx decreased gradually during the period of observation. There was a significant correlation between CSF concentrations of NOx and OxyHb in the entire observation period (R=0.87, p<0.001). When the impact of bleeding into CSF was considered, patients with very good outcome [Glasgow Outcome Scale (GOS)=5] had significantly lower CSF NOx (11.1+/-1.3 microM) than those with worse outcome (GOS<5) (21.8+/-11.2 microM, p<0.01). In conclusion, this study demonstrates that after aneurysm rupture CSF NOx levels correlate with OxyHb. We suggest this as a novel interpretation of other variable findings in relation to NO metabolites in the central nervous system (CNS) post SAH, and hence it could usefully be incorporated into the planning of future studies, correlating NOx with clinical outcome.

Adult↗
PubMed2003

Temporal alterations in cerebrospinal fluid amyloid beta-protein and apolipoprotein E after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The mechanism underlying the association between possession of the APOEepsilon4 allele and less favorable outcome after subarachnoid hemorrhage (SAH) remains to be determined. After SAH the level of apolipoprotein E (apoE) in the cerebrospinal fluid (CSF) is decreased, and lower levels are associated with more severe injury and less favorable outcome. This study examined serial CSF samples to determine the time course for the decrease in CSF apoE and the relationship between CSF apoE and amyloid beta-protein (Abeta), testing the hypothesis that apoE-Abeta interactions occur in vivo after SAH. METHODS: Enzyme-linked immunosorbent assay was used to assay apoE, Abeta1-40, and Abeta1-42 in serial ventricular CSF samples from 19 patients with SAH and 13 controls. CSF S100B and tau were assayed as surrogate markers of brain injury. RESULTS: There was a sustained decrease in CSF apoE (P<0.001) and Abeta (P<0.001) after SAH in contrast to the observed elevation in CSF S100B (P<0.001) and tau (P<0.001) concentration. There was significant correlation between CSF Abeta concentration and clinical outcome (r=0.65, P<0.01), and the decrease in CSF Abeta concentration correlated significantly with that of apoE (r=0.85, P<0.0001). CONCLUSIONS: After SAH both apoE and Abeta levels decrease in the CSF, supporting the concept that interactions between these proteins occur in vivo. The possibility that apoE and Abeta influence outcome after SAH warrants further investigation.

Adolescent↗
PubMed2003

Cannabinoids inhibit neurodegeneration in models of multiple sclerosis.

Multiple sclerosis is increasingly being recognized as a neurodegenerative disease that is triggered by inflammatory attack of the CNS. As yet there is no satisfactory treatment. Using experimental allergic encephalo myelitis (EAE), an animal model of multiple sclerosis, we demonstrate that the cannabinoid system is neuroprotective during EAE. Mice deficient in the cannabinoid receptor CB1 tolerate inflammatory and excitotoxic insults poorly and develop substantial neurodegeneration following immune attack in EAE. In addition, exogenous CB1 agonists can provide significant neuroprotection from the consequences of inflammatory CNS disease in an experimental allergic uveitis model. Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.

Animals↗
PubMed2003

Impaired fibrinolysis in multiple sclerosis: a role for tissue plasminogen activator inhibitors.

Tissue plasminogen activator (tPA), a neuronal as well as the key fibrinolytic enzyme, is found concentrated on demyelinated axons in multiple sclerosis lesions together with fibrin(ogen) deposits. The decreased tPA activity in normal-appearing white and grey matter and lesions of multiple sclerosis is reflected in diminished fibrinolysis as measured by a clot lysis assay. Nonetheless, peptide products of fibrin, including D-dimer, accumulate on demyelinated axons-the result of fibrinogen entry through a compromised blood-brain barrier (BBB). Analysis of tissue samples on reducing and non-reducing polyacrylamide gels demonstrates complexes of tPA with plasminogen activator inhibitor-1 (PAI-1) but not with neuroserpin, a tPA-specific inhibitor concentrated in grey matter. As total tPA protein remains unchanged in acute lesions and the concentration of PAI-1 rises several fold, complex formation is a probable cause of the impaired fibrinolysis. Although the tPA-plasmin cascade promotes neurodegeneration in excitotoxin-induced neuronal death, in inflammatory conditions with BBB disruption it has been demonstrated to have a protective role in removing fibrin, which exacerbates axonal injury. The impaired fibrinolytic capacity resulting from increased PAI-1 synthesis and complex formation with tPA, which is detectable prior to lesion formation, therefore has the potential to contribute to axonal damage in multiple sclerosis.

Adult↗