Cerebrospinal Fluid Creatine Kinase Research Articles

Cerebrospinal Creatine Kinase BB Isoenzyme: A Biomarker for Predicting Outcome After Cardiac Arrest.

Cerebrospinal fluid creatine kinase BB isoenzyme (CSF CK-BB) after cardiac arrest (CA) has been shown to have a high positive predictive value for poor neurological outcome, but it has not been evaluated in the setting of targeted temperature management (TTM) and modern CA care. We aimed to evaluate CSF CK-BB as a prognostic biomarker after CA. We performed a retrospective cohort study of patients with CA admitted between 2010 and 2020 to a three-hospital health system who remained comatose and had CSF CK-BB assayed between 36 and 84h after CA. We examined the proportion of patients at hospital discharge who achieved favorable or intermediate neurological outcome, defined as Cerebral Performance Category score of 1-3, compared with those with poor outcome (Cerebral Performance Category score 4-5) for various CSF CK-BB thresholds. We also evaluated additive value of bilateral absence of somatosensory evoked potentials (SSEPs). Among 214 eligible patients, the mean age was 54.7 ± 4.8years, 72% of patients were male, 33% were nonwhite, 17% had shockable rhythm, 90% were out-of-hospital CA, and 83% received TTM. A total of 19 (9%) awakened. CSF CK-BB ≥ 230 U/L predicted a poor outcome at hospital discharge, with a specificity of 100% (95% confidence interval [CI] 82-100%) and sensitivity of 69% (95% CI 62-76%). When combined with bilaterally absent N20 response on SSEP, specificity remained 100% while sensitivity increased to 80% (95% CI 73-85%). Discordant CK-BB and SSEP findings were seen in 13 (9%) patients. Cerebrospinal fluid creatine kinase BB isoenzyme levels accurately predicted poor neurological outcome among CA survivors treated with TTM. The CSF CK-BB cutoff of 230 U/L optimizes sensitivity to 69% while maintaining a specificity of 100%. CSF CK-BB could be a useful addition to multimodal neurological prognostication after CA.

Creatine kinase and its isoenzymes in the serum and cerebrospinal fluid of healthy canines.

Creatine kinase (CK) exists as three isoenzymes (CK-MM, CK-MB, and CK-BB) that are predominantly expressed in specific tissues and can be detected in both the serum and cerebrospinal fluid (CSF). CSF CK has been relatively unstudied in veterinary medicine, although studies in human medicine have demonstrated that changes in total CSF CK activity can indicate neurologic abnormalities. The purpose of this study was to establish reference intervals for CK and its three major isoenzymes in the serum and CSF of clinically healthy dogs. By establishing a definitive reference interval for this enzyme in healthy canines, the diagnostic use and possible significance of CK in clinical disease can be studied. Serum and/or CSF were collected from healthy dogs. Total CK activity was measured spectrophotometrically, and isoenzyme distributions were determined using the QuickGel CK Vis Isoenzyme Kit and a densitometric scanner. Total CK and CK isoenzyme activities were determined within 8 h of collection. The median serum total CK in healthy canines was 159.0 U/L (range: 53.0-539.0 U/L), while the median CSF total CK was 3.7 U/L (range: 2.0-84.0 U/L). CK-BB and CK-MM were approximately equal in the serum, while CK-MM was the predominant isoenzyme in the CSF. Knowledge of the normal distribution and concentration of CK in canine serum and CSF will set the foundation for future studies of canine CK as a potentially clinically useful biomarker.

Comparison of creatine kinase in cerebrospinal fluid collected from the cerebellomedullary and lumbar cisterna in 10 dogs with neurologic disease

Analysis of cerebrospinal fluid CK (CSF-CK) might be useful as a prognostic indicator in dogs with neurologic disease. Previous studies have mostly analyzed CSF-CK collected from the cerebellomedullary (CM) cisterna, but CSF collection sites could affect its levels. This is a pilot study aimed to evaluate differences in CSF-CK concentrations when collected from the CM or lumbar cisterna in dogs presenting with neurologic disease. Ten dogs presenting for neurologic disease underwent magnetic resonance imaging and CSF collection from both the CM and lumbar cisterna. Cerebrospinal fluid CK was analyzed within 30minutes. Ten dogs were prospectively recruited. Overall, there was no statistically significant difference between CSF-CK collected from the CM or lumbar cisterna (P=.31). When evaluated by neurolocalization, CSF-CK was different between sites in dogs with thoracolumbar myelopathy (P=.024), but not in dogs with intracranial or cervical neurolocalization (P=.93). All dogs with thoracolumbar myelopathy had equivocal or higher CK levels at the lumbar collection site compared with levels at the CM collection site. Cerebrospinal fluid CK values differed depending on the CSF site collection, especially in dogs with thoracolumbar myelopathy. In dogs with thoracolumbar myelopathy, CSF-CK was likely to be higher when CSF was taken from the lumbar cisterna compared with the CM cisterna. Collecting CSF from the thoracolumbar site could provide better prognostic information than if collected at the CM collection site.

Role of cerebrospinal fluid, creatine kinase and lactate dehydrogenase enzyme levels in diagnostic and prognostic evaluation of tubercular and pyogenic meningitis

Background: Etiological diagnosis for meningitis remains a challenge and often a cerebrospinal fluid (CSF) examination may not give the precise diagnosis. Many enzymes are known to be present in abundance in nervous system. In meningitis, nerve tissue damage leads to release of these enzymes into CSF, which may have important diagnostic and prognostic role. Aim was to evaluate the diagnostic and prognostic significance of creatine kinase (CK) and lactate dehydrogenase (LDH) enzymes in CSF of tubercular and pyogenic meningitis.Methods: A prospective case control study of 50 subjects with pyogenic or tubercular meningitis, admitted in Department of Medicine, S.R.N. Hospital, M.L.N.M.C. Allahabad, Uttar Pradesh, India from September 2015-August 2016 was done. Level of CK and LDH were estimated in CSF and serum on day of admission and 7th day. 50 subjects with non-neurological diseases were taken as control.Results: Out of total 50 patients, 36 were of tubercular meningitis and 14 were of pyogenic meningitis. Mean CSF CK and CSF LDH levels were significantly raised in both conditions with respect to controls (p<0.001 and p<0.05 respectively). Mean CSF CK and CSF LDH level were significantly reduced from day of admission to 7th day in both tubercular and pyogenic meningitis patients.Conclusions: Enzymes level in CSF like CK and LDH are significantly raised in pyogenic and tubercular meningitis. Accessing its value can be an important diagnostic and prognostic marker.

Role of CSF CK, LDH, GGTP Enzyme Levels in Diagnostic and Prognostic Evaluation of Meningitis.

Aetiological diagnosis for meningitis remains a challenge and often a thorough Cerebrospinal fluid (CSF) examination may not give a precise diagnosis as at times CSF findings may simulate meningitis like picture as in carcinomatous meningitis, chemical meningitis, early stages of Guillan bare syndrome, subarachnoid hemorrhage, ICSOL, brain abscess, intracranial extension of epidural or subdural infection. Lesions of tissue rich in enzymes may cause enzymatic release on tissue destruction, so also in meningitis and many enzymes are known to be present in abundance in nervous system. To evaluate the diagnostic and prognostic significance of Creatine Kinase (CK), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transpeptidase (GGTP) enzymes in CSF of meningitis. A prospective cases control study of pyogenic and tubercular meningitis patients of 44 cases admitted in department of medicine from September 2011-September 2012 was done. Enzymes like CK, LDH and GGTP were estimated on day 0 (day of admission) and 7th day in the CSF and in serum. CSF and serum CK, LDH, GGTP was estimated on 0th day 0 only in cases of controls. Out of 44 patients, total 32 were tubercular meningitis and 12 were pyogenic meningitis. Mean CSF CK, LDH levels were significantly raised in both conditions with respect to controls in day 0 with p < 0.0001 and p < 0.05 respectively. Mean CSF CK, LDH level were also significantly reduced from 0 to 7th day in both tubercular, pyogenic meningitis, while CSF GGTP was not significantly raised with respect to control in day 0. Enzymes level in CSF like CK, LDH are significantly raised in the meningitis and accessing its value can be an important diagnostic and prognostic marker. But more studies are required to establish the usefulness of estimating these enzymes.

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

To examine associations between CSF biomarkers, initial neurologic dysfunction, and long-term ambulatory outcome in dogs with acute intervertebral disk herniation (IVDH). Prospective clinical study. 54 dogs with acute thoracolumbar IVDH and 16 clinically normal dogs. 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. 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. 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.

Somatosensory potentials, CSF creatine kinase BB activity, and awakening after cardiac arrest.

To examine the utility of somatosensory evoked potential (SEP) peaks and CSF creatine kinase BB isoenzyme activity (CKBB) in predicting nonawakening from coma due to cardiac arrest. Accurate predictors of neurologic outcome in patients comatose after cardiac arrest are needed to improve medical decision making. A total of 72 comatose patients had bilateral median SEPs, and of these, 52 had CSF and CKBB. Awakening was defined as following commands or having comprehensible speech. Both short (N1) and long (N3) latency SEP peaks were analyzed. Nonparametric analyses were used. For patients who had both tests, CKBB > or = 205 U/L predicted nonawakening with a sensitivity of 49% and a specificity of 100%. Bilateral absence of the N1 peak predicted nonawakening with a sensitivity of 53% and a specificity of 100%. Using CKBB > or = 205 U/L, bilaterally absent SEP N1 peaks, or both predicted nonawakening with a sensitivity of 69% and a specificity of 100%. Using CKBB > or = 205 U/L, bilaterally absent N1 peaks, bilateral N3 > or = 176 msec or absent, or some combination predicted nonawakening with a sensitivity of 78% and a specificity of 100%. The combination of an absent N1 peak and elevated CKBB performs better than either alone in predicting nonawakening after cardiac arrest. Prolonged or absent N3 latency may increase sensitivity. These results should be interpreted with caution given the small number of patients and the possibility of a self-fulfilling prophecy.

Changes in the Creatine Kinase and Lactate Dehydrogenase Activities in Cerebrospinal Fluid of Dogs with Thoracolumbar Disc Disease

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Cerebrospinal fluid creatine kinase BB isoenzyme activity and neurologic prognosis after cardiac arrest

Cerebrospinal fluid creatine kinase BB isoenzyme activity and neurologic prognosis after cardiac arrest

High-dose phenobarbital therapy in term newborn infants with severe perinatal asphyxia: A randomized, prospective study with three-year follow-up

Objective: To determine whether 40 mg/kg phenobarbital given to term infants with severe asphyxia would result in a lower incidence of seizures in the newborn period and an improved neurologic outcome. Methods: We conducted a randomized, controlled, prospective study. Entry criteria included (1) an initial arterial pH less than or equal to 7.0 with a base deficit 15 mEq/L or more, (2) Apgar score less than or equal to 3 at 5 minutes of age, or (3) failure to initiate spontaneous respiration by 10 minutes of age. Sample size was calculated to detect a 50% reduction in the incidence of neonatal seizures. Results: No differences were present between treatment and control groups with respect to severity of asphyxia assessed by initial arterial pH, base excess, cerebrospinal fluid lactate dehydrogenase concentration or detection of CSF creatine kinase of its BB isoenzyme. Seizures occurred in 9 of 15 infants in the treatment group and 14 of 16 infants in the control group ( p = 0.11). No adverse effects were observed from phenobarbital on heart rate, respiratory rate, blood pressure, or arterial blood gas values. Three-year follow-up revealed normal outcome in 11 of 15 infants in the treatment group and 3 of 16 in the control group ( p = 0.003). Conclusion: Phenobarbital, when administered in a dose of 40 mg/kg intravenously over 1 hour in term, severely asphyxiated newborn infants appeared to be safe and was associated with a 27% reduction in the incidence of seizures and a significant improvement in neurologic outcome at 3 years of age. (J Pediatr 1998;132:345-8)

Cerebrospinal fluid creatine kinase BB isoenzyme activity and neurologic prognosis after cardiac arrest.

To assess the relationship between CSF creatine kinase BB isoenzyme activity (CSF CKBB) and neurologic outcome after cardiac arrest in clinical practice. CSF CKBB reflects the extent of brain damage following cardiac arrest. To help with prognosis, treating physicians ordered CSF CKBB tests on 474 patients over 7.5 years; 351 of these patients had experienced a cardiac arrest. Assays were performed in one laboratory using agarose electrophoresis. By chart review, we determined awakening status for all patients, defined as the patient having comprehensible speech or following commands. CSF CKBB was usually sampled 48 to 72 hours after cardiac arrest and was strongly associated with awakening (p < < 0.001). The median was 4 U/l for 61 patients who awakened and 191 U/l for 290 who never awakened. For those who awakened, 75% of CKBB levels were < 24 U/l, and for those who never awakened, 75% were > 86 U/l. The highest value in a patient who awakened was 204 U/l, a cutoff that yielded a specificity of 100% of never awakening but a sensitivity of forty-eight percent. Only nine patients who awakened had CSF CKBB values greater than 50 U/l, and none regained independence in activities of daily living. Only three unconscious patients were still alive at last contact, with follow-up of 63, 107, and 109 months. Using logistic regression, the probability of never awakening given a CSF CKBB result can be estimated as: 1/(1 + L), where L = e raised to (0.1267 - 0.0211 x CSF CKBB [U/l]). CSF CKBB measurement helps to estimate degree of brain damage and thus neurologic prognosis after cardiac arrest. However, results of this retrospective study could reflect in part a self-fulfilling prophecy.

The diagnostic utility of cerebrospinal fluid creatine kinase activity in the horse.

We evaluated creatine kinase (CK) activity in the cerebrospinal fluid (CSF) of 128 horses with various neurological disorders. No association was found between CSF CK activity and CSF red blood cell count, CSF nucleated cell count, CSF total protein concentration, or serum CK activity. The sensitivity and specificity of CSF CK activity as a diagnostic test for protozoal myelitis in horses (61% and 56%, respectively) was higher than for cervical stenotic myelopathy, degenerative myelopathy, or motor neuron disease, but was considered to be inadequate to be of use diagnostically. Contamination of CSF with whole blood, hemolyzed red blood cells, or serum did not substantially contribute to increases in CSF CK activity. Addition of epidural fat or dura to CSF significantly increased CSF CK activity in all cases. We suggest that the use of CSF CK activity as a diagnostic indicator of neurological disease in the horse in unreliable, and that CSF CK activity may be falsely increased by contamination of CSF with epidural fat or dura during CSF collection.

Creatine kinase BB and neuron-specific enolase in cerebrospinal fluid in the diagnosis of brain insult.

Cerebrospinal fluid (CSF) markers provide useful information about the extent of brain damage. These biochemical indices may also be used when postmortem histopathological examination does not confirm antemortem brain insult. Seven biochemical parameters--creatine kinase (CK), creatine kinase BB isoenzyme (CK-BB), lactate dehydrogenase (LDH), gamma-glutamyltransferase, aldolase, leucine aminopeptidase (LAP), and neuron-specific enolase (NSE)--were analyzed in CSF from 82 cadavers. Case studies were categorized into one of four diagnostic groups. There were 15 cases of head trauma, 23 of hypoxia (hangings, carbon monoxide, and drug poisonings), 23 sudden cardiac death, and 21 miscellaneous cases. The degree of craniocerebral trauma was graded. In CSF there was a statistically significant correlation between the severity of craniocerebral trauma and levels of CK, CK-BB, aldolase, LDH, and LAP. CSF CK-BB [median U/L (range)] for the groupings of head trauma, hypoxia, sudden cardiac death, and miscellaneous were, respectively, 873 (1-12,100), 26 (2-2,780), 16 (1-42), and 18 (0-2,780). Corresponding CSF CK levels were 9,370 (28-67,842), 101 (18-36,840), 180 (10-29,622), and 264 (17-26,556). There were no statistical significant differences among the NSE concentrations in the four diagnostic groups. The testing of biochemical markers could be a reliable indicator of the degree of brain insult in support of morphological studies.

Composition and analysis of cerebrospinal fluid in clinically normal adult cattle

Summary Cerebrospinal fluid and serum were obtained from 16 clinically normal adult cows (11 dairy, 5 beef). Sodium, potassium, magnesium, total protein, and albumin concentrations, osmolality, and lactate dehydrogenase and creatine kinase activities, were quantified in csf and serum. Total and differential cell counting, protein electrophoresis, and IgG quantification were performed on csf. Statistical analyses of these variables, including mean, sem, range, and 95% confidence intervals, were performed. Effects of blood contamination were evaluated, and were found to be negligible for all measured constituents. Correction factors for csf creatine kinase and lactate dehydrogenase activities accounting for cellular contamination were developed. Total nucleated cell count was similar to counts in csf of other species, but higher than values in healthy people. Differential leukocyte count in csf was similar to that reported in csf of other domestic animals: mostly lymphocytes, fewer monocytoid cells, and scant neutrophils. Cerebrospinal fluid protein concentration was higher than concentration reported for dogs, goats, and people, but was similar to values reported for horses. Beef cows had higher csf total protein concentration than did dairy cows; also, beef cows had higher csf γ-globulin concentration. The concentration of sodium in csf was slightly higher than the value in serum, and potassium concentration was lower than the value in serum. In contrast to studies of human beings, csf osmolality was generally less than serum osmolality in the cows studied. Reference values for csf electrolyte concentrations and osmolality are useful for diagnosis of salt poisoning and for assessment of the effects of fluid therapy. Magnesium concentration was lower in csf, compared with serum. Reference values may be useful for diagnosis of grass tetany. Glucose concentration in csf was variable, compared with serum concentration; sometimes, it was similar, lower, or even higher than serum glucose concentration. This variation reflects a more complete equilibration of glucose between csf and blood, owing to the lower and more stable blood glucose concentration in cows. Creatine kinase activity in csf was markedly less than, and was not correlated with, serum creatine kinase activity. Cerebrospinal fluid lactate dehydrogenase activity was markedly lower than serum lactate dehydrogenase activity. Compared with lactate dehydrogenase, creatine kinase activity had a wider range in these healthy cows; therefore, the former enzyme has higher specificity and sensitivity for diagnosis of diseases affecting the cns.

Evaluation of hypoxic brain injury with spinal fluid enzymes, lactate, and pyruvate.

To investigate the prognostic importance in neurologic recovery of the lumbar cerebrospinal fluid (CSF) variables creatine kinase (CK) and brain-type creatine kinase isoenzyme (CK-BB), lactate dehydrogenase (LDH) and its isoenzymes (LDH 1-5), CSF acid phosphatase, beta-D-N-acetylglucosaminidase activity, and CSF lactate, pyruvate, sodium, potassium, and calcium concentrations in patients who experienced cardiac arrest. Prospective clinical study with blood and CSF samples collected 4, 28, 76, and 172 hrs after resuscitation. Medical ICU in a university hospital. Twenty consecutive victims of out-of-hospital cardiac arrest. Eight patients recovered neurologically and 12 patients remained comatose or neurologically disabled until death. CSF CK, CK-BB, LDH, and LDH isoenzyme 1-3 concentrations in all disabled patients were markedly increased at 76 hrs after the resuscitation. However, these variables were not changed in the recovered subjects. Patients (n = 7) with a mean CSF CK level of 25 +/- 33 (SD) U/L, CK-BB 23 +/- 33 U/L, and CSF lactate 3.8 +/- 0.9 mmol/L at 28 hrs after cardiac arrest remained unconscious and died. In the recovered patients, the mean CSF CK concentration was 2.0 +/- 1.5 U/L (p less than .001) and CSF lactate concentration 2.5 +/- 0.5 mmol/L (p less than .002). The lactate concentration was highest at 4 hrs after resuscitation, declining thereafter. Patients with a mean CSF total LDH level of 609 +/- 515 U/L and acid phosphatase 2.4 +/- 1.2 U/L 76 hrs after resuscitation died without regaining consciousness. In the recovered patients, the mean total CSF LDH activity was 82 +/- 58 U/L (p = .003) and CSF acid phosphatase was 0.8 +/- 0.5 U/L (p = .01) 76 hrs after resuscitation. CSF CK, CK-BB, and CSF lactate concentrations reflect a patient's outcome most reliably when measured within 28 to 76 hrs of the cardiac arrest. Similarly, CSF LDH, its isoenzymes 1-3, and CSF acid phosphatase concentrations, when measured at 76 hrs, can be used to monitor the patient's outcome after cardiac arrest. When correlated with Glasgow Coma Scale scores, the closest negative correlation was again seen in CSF CK and CK-BB at 28 and 76 hrs, as well as in LDH, LDH1-3, and acid phosphatase values at 76 hrs. The negative correlation between CSF lactate and Glasgow Coma Scale scores was most distinct at 28 hrs.

Cerebrospinal fluid creatine kinase activity in horses with central nervous system disease: 69 cases (1984-1989)

Summary The csf creatine kinase (ck) activity was determined in 70 csf samples from 69 horses with cns disease. Abnormal values (≥ 1 IU/L) were determined from 32 csf samples, and normal values (&lt;1 IU/L) were found in 38 samples. Increased ck activity was most frequently associated with a diagnosis of equine protozoal myelitis; ck activity was not increased in 11 horses with cervical compressive myelopathy. Other diagnoses, in which csf ck activity was increased included trauma (n = 1), idiopathic epilepsy (n = 2), botulism (n = 2), articular facet fracture (n = 1), intervertebral disk protrusion (n = 1), and toxemia (n = 1).

Neuronal‐Visceral GM1 Gangliosidosis in Portuguese Water Dogs

Three female siblings in a litter of seven Portuguese Water dogs (PWDs) showed clinical signs of ataxia and/or lameness at 5 months of age. Signs of cerebellar dysfunction (intention tremors, ataxia, widebased stance, dysmetria, and/or nystagmus) and mild limb weakness developed rapidly. Results of hemograms (three dogs), blood chemistry profiles (two dogs), urinalyses (two dogs), electroencephalograms (two dogs), and radiographs of the limbs or pelvis (three dogs), vertebrae (two dogs), and skull (one dog) were unremarkable except for an absolute lymphocytosis in one dog. Routine cerebrospinal fluid (CSF) analyses were normal in all three dogs. However, the CSF creatine kinase concentration was elevated in the one dog in which it was measured. Mucopolysacchariduria was present in all three dogs. Due to the rapid progression of clinical signs and a poor prognosis, all three dogs were euthanatized between 6 and 7 months of age. Histopathologic and electron microscopic studies showed neuronal cytoplasmic inclusions, vacuolated hepatocytes, and vacuolated renal tubular epithelial cells, compatible with the diagnosis of a storage disease. Beta-galactosidase activities in leukocytes, serum, and brain homogenates were reduced when compared with that in normal dogs and the stored product was identified as GM1 ganglioside, confirming GM1 gangliosidosis.

Cerebrospinal fluid creatine kinase isoenzyme BB levels do not predict the clinical outcome in patients unconscious following cardiac resuscitation.

It has recently been claimed that an increase in creatine kinase isoenzyme BB(CK-BB) in cerebrospinal fluid (CSF) is well correlated with the cerebral outcome in patients resuscitated after cardiac arrest. Twenty-one such patients consecutively admitted from outside this hospital participated in the study. The patients were divided into two groups: 6 survivors and 15 nonsurvivors. The median CSF-CK-BB value was 5 U/L among nonsurvivors and below detection limit among survivors (NS). However, the predictive value of a positive test is limited, since only 6 of 15 nonsurvivors (40%) had an increase in CSF-CK-BB (predictive value of positive test = 67%). The predictive value of a negative test is limited, since 3 of 6 survivors (50%) showed no rise in CSF-CK-BB (predictive value of negative test = 25%). No relationship between cerebral dysfunction and CSF-CK-BB values was revealed. Thus, CSF-CK-BB does not predict the clinical outcome in patients resuscitated after cardiac arrest.

Mitochondrial and MB isoenzymes of creatine kinase in cerebrospinal fluid from patients with hypoxic-ischemic brain damage.

Measurements of cerebrospinal fluid (CSF) creatine kinase (CK, EC 2.7.3.2) isoenzyme activity have been used to predict outcome in patients with acute brain injury following cardiac arrest. We identified two CK isoenzymes previously unreported in CSF from 16 patients with hypoxic-ischemic brain damage. Prior to analysis, the CK in the CSF samples was reactivated with dithiothreitol. CK isoenzymes were identified using electrophoretic and immunologic methods. Total CK activity ranged from 23 to 924 U/L (mean 452). CSF-CK-BB was the predominant isoenzyme present in all cases. In addition to CSF-CK-BB, the authors identified CSF-CK-MM in 6 cases, CSF-CK-MB in 8 cases, and CSF-mitochondrial-CK in 14 cases. The presence of CSF-CK-MM was significantly related to blood contaminating the CSF (P less than 0.02). It is proposed that CSF-CK-MB results from recombination of CK-MM and CK-BB in CSF and that mitochondrial CK is released with CK-BB into the CSF from the damaged brain tissue.

Creatine Kinase Brain Isoenzyme: Relationship of Cerebrospinal Fluid Concentration to the Neurologic Condition of Newborns and Cellular Localization in the Human Brain

Immunocytochemical study of human brain showed creatine kinase brain isoenzyme (CKBB) present in both neurons and astrocytes. Because creatine kinase brain isoenzyme is an intracellular enzyme that might be released with brain injury, its concentration in the CSF of newborns was measured using a radioimmunoassay. Infants who suffered a documented neurologic insult (a cerebroventricular hemorrhage or a CNS infection) were found to have a greater mean CSF creatine kinase brain isoenzyme concentration than those without a history of neurologic insult. Infants with a high concentration had a poor short-term outcome (death or neurologic abnormality when discharged) more frequently than did those with a lower concentration. Infants with a grade 3 or 4 cerebroventricular hemorrhage had a higher mean concentration than did those with a grade 1 or 2 hemorrhage. These data are consistent with the hypothesis that CSF creatine kinase brain isoenzyme is a metabolic indicator of brain damage in newborns.