Associations between cerebrospinal fluid biomarkers and long-term neurologic outcome in dogs with acute intervertebral disk herniation.

OBJECTIVE: To examine associations between CSF biomarkers, initial neurologic dysfunction, and long-term ambulatory outcome in dogs with acute intervertebral disk herniation (IVDH). DESIGN: Prospective clinical study. ANIMALS: 54 dogs with acute thoracolumbar IVDH and 16 clinically normal dogs. PROCEDURES: For each dog, variables, including CSF myelin basic protein (MBP), lactate, calcium, glucose, and total protein concentrations; nucleated cell count; and creatine kinase (CK) and aspartate aminotransferase activities, were measured. For dogs with thoracolumbar IVDH, initial neurologic function was characterized by use of a modified Frankel score (MFS; determined on a scale of 0 to 5, where 0 represented paraplegia with no deep nociception and 5 represented paraspinal hyperesthesia only). Long-term follow-up was assessed. RESULTS: Among dogs with thoracolumbar IVDH, those with CSF CK activity ≤ 38 U/L had a 35-fold increase in the odds of long-term ambulation, compared with the odds in dogs with CSF CK activity > 38 U/L, adjusting for neurologic functioning at the evaluation. The CSF lactate, calcium, and glucose concentrations and aspartate aminotransferase activity were not predictive of long-term ambulatory outcome. Data analysis revealed that long-term functional recovery was > 98% for affected dogs, regardless of their initial MFS, when CSF CK activity was ≤ 38 U/L and MBP concentration was ≤ 3 ng/mL. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with acute thoracolumbar IVDH, CSF CK activity and MBP concentration appeared to be prognostic indicators and, along with initial MFS, can be used to predict long-term ambulatory outcome.

Cerebrospinal fluid biomarkers showing neurodegeneration in dogs with GM1 gangliosidosis: possible use for assessment of a therapeutic regimen.

The present study investigated cerebrospinal fluid (CSF) biomarkers for estimating degeneration of the central nervous system (CNS) in experimental dogs with GM1 gangliosidosis and preliminarily evaluated the efficacy of long-term glucocorticoid therapy for GM1 gangliosidosis using the biomarkers identified here. GM1 gangliosidosis, a lysosomal storage disease that affects the brain and multiple systemic organs, is due to an autosomal recessively inherited deficiency of acid beta-galactosidase activity. Pathogenesis of GM1 gangliosidosis may include neuronal apoptosis and abnormal axoplasmic transport and inflammatory response, which are perhaps consequent to massive neuronal storage of GM1 ganglioside. In the present study, we assessed some possible CSF biomarkers, such as GM1 ganglioside, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and myelin basic protein (MBP). Periodic studies demonstrated that GM1 ganglioside concentration, activities of AST and LDH, and concentrations of NSE and MBP in CSF were significantly higher in dogs with GM1 gangliosidosis than those in control dogs, and their changes were well related with the months of age and clinical course. In conclusion, GM1 ganglioside, AST, LDH, NSE and MBP could be utilized as CSF biomarkers showing CNS degeneration in dogs with GM1 gangliosidosis to evaluate the efficacy of novel therapies proposed for this disease. In addition, we preliminarily treated an affected dog with long-term oral administration of prednisolone and evaluated the efficacy of this therapeutic trial using CSF biomarkers determined in the present study. However, this treatment did not change either the clinical course or the CSF biomarkers of the affected dog, suggesting that glucocorticoid therapy would not be effective for treating GM1 gangliosidosis.

Amino acids and transaminases activity in ventricular CSF and in brain of normal and Alzheimer patients.

The present study was conducted to determine the concentration of amino acids in the cerebrospinal spinal fluid (CSF) and the activities of two tramsaminases: glutamic oxaloacetate transaminase (GOT) and glutamic pyruvate transaminase (GPT) in human Alzheimer disease (AD) and normal brain. L-glutamic acid, L-glutamine and L-alanine are the most abundant amino acids in the CSF (50-55% of total amino acids). L-glutamine occurs at much higher levels in Alzheimer CSF compared to the normal CSF (229+/-91.8 nmol/ml in AD versus 107+/-47.2 nmol/ml in normal; P=0.0041). In contrast, L-aspartate occurs at significantly lower concentrations in Alzheimer CSF than normal CSF (46.1+/-25.7 nmol/ml in Alzheimer versus 95.2+/-52.6 nmol/ml in normal; P=0.020). In Alzheimer brain (frontal, parietal and occipital cortices) GOT is present at significantly higher activities than in normal brain cortices (about 1.5 times higher; P<0.01). No significant differences for GPT activity occurred between normal and AD brain. Since CSF receives amino acids from brain tissues, and since GOT catalyzes the conversion of L-aspartate to L-glutamate, the higher concentrations of L-glutamine (which is derived from L-glutamate), and the lower concentrations of L-aspartate found in Alzheimer CSF could be considered as a consequence of the higher activity of GOT that occurs in Alzheimer brain.

Systematic review of prediction of poor outcome in anoxic-ischaemic coma with biochemical markers of brain damage.

OBJECTIVE: To investigate whether accurate prognostic rules can be derived from the combined results of studies concerning prediction of poor prognosis in anoxic-ischaemic coma with biochemical markers of brain damage in cerebrospinal fluid (CSF) or serum. DESIGN: A meta-analysis of prognostic studies in anoxic-ischaemic coma, selected from Medline and EMBASE databases, according to predefined criteria. SUBJECTS: Twenty-eight studies, with a total of 802 unselected, consecutive patients, in which tests, sampling time and outcome measures were described unequivocally and results were described using clear cut-off values or raw data. MAIN OUTCOME MEASURES: Poor outcome, defined as death or vegetative state, versus good outcome, defined as any other outcome state. ANALYSES: The overall prognostic accuracy of these variables was expressed as the 95% CIs of the pooled false-positive test rate and the pooled positive-likelihood ratios. RESULTS: Only markers in CSF (creatine kinase isoenzyme (CKBB) >204 U/l, neuron specific enolase (NSE) >33 ng/ml, lactate dehydrogenase (LDH) >82 U/l and glutamate oxaloacetate (GOT) >62 U/l) reached a 0% false-positive rate. However, due to small sample sizes, the confidence limits were wide. The accuracy of prediction of poor outcome seemed acceptably high for CSF-CKBB (pooled false-positive rate 0% [95% CI 0-2.3%]; pooled positive-likelihood ratio 33.2 [95% CI 4.8-230.2]), but this result was based on two retrospective studies without blinding of the treating physicians for the test result. CONCLUSIONS: Because of small numbers of patients studied and methodological limitations the combined results are not sufficiently accurate to provide a solid basis for non-treatment decisions.

[Enzyme activity in the cerebrospinal fluid in patients with brain gliomas]. / Aktivnost' fermentov v likvore u bol'nykh s gliomami golovnogo mozga.

The spinal fluid activities of aspartate aminotransferase (AAT), alkaline phosphatase (AP), and gamma-gluthamyl transferase were studied in 32 patients with cerebral gliomas to clarify the diagnostic role of these enzymes. There were different changes in their activities in groups of patients with low-differential and differential gliomas. Its was ascertained that higher AAT activity was due to the fact that blood had entered spinal fluid; increased AP activity may be regarded to be an indicator of higher permeability of the blood-brain barrier.

Evaluation of hematological, serum biochemical and cerebrospinal fluid parameters in experimental bacterial meningitis in the calf.

To evaluate the effects of bacterial meningitis on blood and CSF parameters, an experiment was conducted with five Iranian crossbred male calves. Blood and CSF samples were collected 3 times within a 5-day interval before the administration of bacteria for obtaining control values. Following the injection of E. coli, K12 into the cerebrospinal fluid from the lumbosacral space, samples were collected and clinical signs of meningitis were observed. Blood and CSF samples were obtained from the meningitis group 3 times at 1, 3, and 5 days post injection. The treatment of the infected calves using lincospectin and tetracycline was carried out immediately after the onset of clinical signs. After the treatment, blood and CSF samples were obtained 3 times during a 5-day period. Following the induction of meningitis, the number of WBCs, neutrophils, eosinophils and monocytes significantly increased (P < 0.05). However, the percent of lymphocytes decreased significantly (P < 0.05). The concentrations of glucose, potassium and activity of AST, LDH, CK significantly increased (P < 0.05). In contrast, the concentrations of phosphorous, sodium and magnesium significantly decreased (P < 0.05). Furthermore, following the induction of meningitis, the CSF was slightly xantochromic and turbid. The concentrations of protein, cholesterol, phosphorous, potassium, the activities of AST, LDH, CK, and the cell numbers in the CSF increased significantly (P < 0.05). In contrast, the concentration of glucose and pH in the CSF decreased significantly (P < 0.05). This study showed that bacterial meningitis can have profound effects on blood and CSF parameters which enable one to reach diagnosis.

The use of cytosolic enzyme increase in cerebrospinal fluid of patients resuscitated after cardiac arrest. Brain Resuscitation Clinical Trial I Study Group.

Levels of brain creatine phosphokinase (CPK), glutamic oxalic transaminase, lactate dehydrogenase, and lactate in lumbar cerebrospinal fluid (CSF) were analyzed as an adjunctive study in a randomized clinical trial evaluating the effects of thiopental loading intravenously in comatose survivors of cardiac arrest. Three hospitals participated and a total of 62 cases of enzyme changes were studied. Enzyme levels but not lactate were higher at 48 hours than at 24 hours after restoration of spontaneous circulation. All enzymes were highly correlated with one another at 24 and 48 hours (P < .001). There was a significant negative correlation between cerebral recovery and increased CPK levels at 24 hours (P < .05), and a highly significant correlation with all three enzyme levels at 48 hours (P < .0001). The increase of cytosolic enzyme activity in lumbar CSF reflects permanent brain damage, and there is a relationship between activity levels and cerebral outcome.

Enzymatic changes in the cerebrospinal fluid in patients with infections of the central nervous system.

Enzymatic determinations in cerebrospinal fluid (CSF) of aspartate aminotransferase (AST), lactic dehydrogenase (LDH), gammaglutamyl transpeptidase (GGT), creatine phosphokinase (CPK) and creatine kinase BB (CK-BB) were performed in 16 patients with aseptic meningitis (AM), in 25 children with bacterial meningitis (BM) and in 15 patients with meningism. The activity of AST and GGT was significantly higher in patients with BM on admission compared with those with AM and meningism (p < 0.05 and p < 0.005, respectively) and decreased with therapy. The highest concentration of AST and LDH appeared in patients with poor outcome as well as in those with ventriculomegaly on neurosonography (p < 0.05). The concentration of CK-BB increased in all patient groups on admission and remained higher on termination of therapy. The present study confirms the high activity of AST and GGT in BM patients in the CSF whereas the increased activity of AST and LDH reflects the extent of brain injury. Nevertheless, the prognosis for individual patients cannot be established on the basis of enzyme activity alone, but depends on several factors.

Clinical, cerebrospinal fluid, and histological data from thirty-four cats with primary noninflammatory disease of the central nervous system.

The purpose of this study was to report the clinical, cerebrospinal fluid (CSF), and histological data derived from a study of 34 cats with noninflammatory central nervous system (CNS) disease, and to report the activities of the enzymes lactate-dehydrogenase (LDH), aspartate transferase (AST), and creatine kinase (CK) in the CSF from 15 cats with a variety of CNS diseases. The cats were part of a study of 61 cats that were admitted to two university clinics because of signs of CNS disease. The most frequent noninflammatory diseases were neoplasia (n = 12) and ischemic encephalopathy (n = 4). The majority of cats with CNS neoplasia had a mild increase in CSF protein concentration (less than 1 g/L [100 mg/dL]), an increased percentage of neutrophils or lymphocytes, and a normal total white cell count. Cats with ischemic encephalopathy (IE) had a mild to moderate increase in CSF protein concentration (< or = 2 g/L [200 mg/dL]) and a mild increase in white cell count (< or = 10 cells/microL) with an increased percentage of lymphocytes. The enzymes LDH, AST, and CK in the CSF were not sensitive indicators of chronic CNS disease. The CSF differential cell count was frequently abnormal when the total white cell count was normal, and blood contamination in the CSF samples was a frequent problem that had to be considered in the interpretation of the results. The history, signalment, and clinical signs, when combined with the CSF findings, were valuable in the diagnosis of noninflammatory CNS disease.

[Changes in the biochemical composition of the cerebrospinal fluid in acute carbophos poisoning]. / Izmeneniia biokhimicheskogo sostava tserebrospinal'noi zhidkosti pri ostrom otravlenii karbofosom.

As far as the pathogenesis of poisonings with organophosphorus pesticides is concerned, in addition to irreversible inhibition of acetylcholinesterase (AGE) in tissues, of importance are changes in the other systems which essentially determine the outcome of intoxication. The purpose of the present study was to examine the nature of changes occurring in total protein and protein fractions, free amino acids (aspartic and glutamic acids, glycine, isoleucine, leucine) and in certain enzymes (AST, ALT, CP, GGTP, GDH) in the cerebrospinal fluid (CSF) of patients with acute Malathion insecticide poisoning. 137 patients aged 20 to 50 years were placed under observation. There were 77 men and 60 women. 40 persons had poisoning of medium gravity and 97 were severely poisoned. The intake of the CSF was performed on days 1, 3, 10, 14 and 21 since the disease onset. It has been established that in acute Malathion insecticide poisoning, the CSF content of the stimulating mediator amino acids, aspartic and glutamic, rises within the early periods, whereas the concentration of the inhibitory mediator glycine decreases. The changes in protein fractions of the CSF are characterized by a fall of the content of globulins and a rise of albumins, thus attesting to the predominance of pathological processes in the brain, especially in the initial period of intoxication, and to the impairment of the blood-brain barrier. The development of intoxication is associated with activation in the CSF of LDN, CP, GGTP and GDH as well as by activation of LDH isozymes which is viewed as the result of the membranotoxic effect of a Malathion insecticide.

Efficacy of cerebro-spinal fluid biochemistry in the diagnosis of brain insult.

Postmortem biochemical indices may provide a useful adjunct to morphological studies in the identification of antemortem brain insult. We studied 34 routine medico-legal cases categorising them into one of four diagnostic groups. There were 11 cases of head trauma, 7 of 'hypoxia' (3 hangings and 4 carbon monoxide or drug poisonings), 7 sudden cardiac deaths and 9 miscellaneous cases. Survival time and postmortem interval was known for each case. The degree of cranio-cerebral trauma was graded. Cerebro-spinal fluid (CSF) and vitreous humour were analysed for calcium, glucose, total proteins, aldolase, aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyltransferase (GGT), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase BB isoenzyme (CK-BB). CK-BB was also measured in superior vena cava serum. In CSF there was a significant correlation between the severity of cranio-cerebral trauma and levels of aldolase, CK-BB, AST, ALT and total proteins. CSF CK-BB, median units/l (range), for the groupings of head trauma, hypoxia, sudden cardiac death and miscellaneous were respectively 823 (2-3431); 96 (2-187); 4 (2-25); 5 (1-69). Corresponding serum CK-BB levels were 240 (28-322); 390 (26-411); 180 (20-482); 79 (18-530).

[Various biochemical indicators of the cerebrospinal fluid in acute carbophos poisoning]. / Nekotorye biokhimicheskie pokazateli tserebrospinal'noi zhidkosti pri ostrom otravlenii karbofosom.

The study was performed to evaluate the levels of some enzymes (AST, ALT, HGTP, LDG) and free amino acids (aspartic, glutaminic, glycine, isoleucine, leucine) in liquor of 37 subjects who got poisoned with a Malathion insecticide. Their condition was diagnosed as moderate and severe. The liquor was obtained on poisoning day 1, 3, 10, 14 and 21. The liquor levels of enhancement mediatory amino acids, aspartic and glutaminic, rise early in poisoning, while concentration of inhibition mediator glycine tends to decline. Progress of intoxication brings about a rise in LDG and GGTP activity attributed to a membranotoxic effect of the insecticide.

Study of serum and cerebrospinal fluid enzymes in diagnosis and differential diagnosis of cerebrovascular diseases.

In the paper are presented the results of total enzyme activity investigation: GOT, GPT, LDH and CPK, and of the CPK isoenzymes in the cerebrospinal fluid of 148 examinees and in the serum of 67 examinees with an acute stroke, who were treated at the Intensive Care Unit of the Department of Neurology and Institute of Neuropathology, Clinical Medical center "Rebro". The aim was to determine the reliability of the applied methods in the diagnosis of cerebrovascular diseases, particularly in the differential diagnosis of cerebral hemorrhage, ischemia and subarachnoidal hemorrhage. The highest frequency of pathologic findings of the tested enzymes in the whole group of patients with CVA was obtained in the determination of the CPK total activity assessment, then followed the assessments of LDH activity, isoenzyme CPK profile, GOT and finally GPT activity. A larger number of pathologic findings of all mentioned enzymes and CPK isoenzymes was found in the group of patients with ICH. In the patients with ICH and ISI, who survived stroke a higher incidence of normal findings of the total enzymic activities was found, while in those who died from ICH a higher incidence of pathologic findings could not be established. The correlations between the total CPK activity in the serum and in the cerebrospinal fluid does not exist, as well as the correlation between the CPK isoenzyme profile in the serum and CSF.

[Enzymologic diagnosis of cerebral lesions in generalized forms of meningococcal infection in the acute period]. / Enzimologicheskaia diagnostika porazhenii golovnogo mozga pri generalizovannykh formakh meningokokkovoi infektsii v ostrom periode zabolevaniia.

Cerebrospinal fluid was tested for several enzymes (CPK, AST, GGTP, BP, BG, AK) in 97 patients with generalized meningococcal infection with prevalent CNS affliction. Marked changes were detected even in the absence of clinical signs of cerebral lesion that was typical only of meningococcemia. Nevertheless, most pronounced changes were observed in a group of patients with cerebral edema and swelling. The changes in cerebrospinal fluid enzyme levels coincided with a reduced glucose and increased protein contents. In these cases, CSF hypertension increased CSF pressure to maximal levels. Most informative indices were singled out and their levels characteristic of acute phase of the disease established.