Precise detection of the germinomatous component of intracranial germ cell tumors of the basal ganglia and thalamus using placental alkaline phosphatase in cerebrospinal fluid.

PURPOSE: The disadvantages of biopsy for lesions in the basal ganglia and thalamus include a risk of various complications, difficulty in selecting the target tissue in some cases due to indistinct neuroimaging findings and limited availability of sample tissue. Placental alkaline phosphatase (PLAP) plays a decisive role in the diagnosis and management of intracranial germ cell tumors (IGCTs) in the basal ganglia and thalamus. The present study aimed to demonstrate the ability, specificity, and optimal use of PLAP values obtained from cerebrospinal fluid (CSF). METHODS: Twenty patients with lesions in the basal ganglia and thalamus were enrolled in this study: 11 had IGCTs and 9 had non-IGCTs. The values of PLAP and other established tumor markers in the CSF were measured in all patients before treatment. RESULTS: The mean follow-up period was 76.0 months (range, 3-168) for all lesions. PLAP was elevated in all 11 patients with IGCTs in the basal ganglia or thalamus, whereas none of the patients with non-IGCT exhibited elevated PLAP. Thus, the sensitivity and specificity of PLAP were both 100%. CONCLUSION: Our data demonstrated that the PLAP value can specifically identify the germinomatous component even in cases of IGCTs in the basal ganglia or thalamus with high sensitivity and specificity. PLAP is undoubtedly beneficial for the safe and timely detection of the germinomatous component of IGCTs in the basal ganglia and thalamus, because reliance on PLAP measurement enables us to avoid invasive surgical procedures and facilitates the prompt initiation of chemoradiation therapy.

Diagnostic Capability of Cerebrospinal Fluid-Placental Alkaline Phosphatase Value in Intracranial Germ Cell Tumor.

OBJECTIVE: Most types of intracranial germ cell tumors (IGCTs) are sensitive to chemoradiation. However, biopsy specimens are usually small and thus cannot be used for obtaining an accurate pathological diagnosis. Recently, the cerebrospinal fluid (CSF) placental alkaline phosphatase (PLAP) value has been considered a new biomarker of IGCTs. The present study aimed to evaluate the discriminatory characteristics of the CSF-PLAP value upon diagnosis and at the time of recurrence in patients with IGCTs. METHODS: Between 2015 and 2019, this study included 37 patients with tumors located in the intraventricular and/or periventricular region. The CSF-PLAP level was assessed before the patients received any treatment. The PLAP level was evaluated during and after first-line chemoradiotherapy in 7 patients with IGCTs. The CSF-PLAP values were compared according to histological diagnosis, and the correlation between these values and radiographical features was assessed. The CSF-PLAP values of 6 patients with IGCTs with suspected recurrence were evaluated based on neuroimaging findings. RESULTS: The CSF-PLAP values were significantly higher in patients with IGCTs than in those with other types of brain tumor (n = 19 vs. 18; median: 359.0 vs. <8.0 pg/mL). The specificity and sensitivity were 88 and 95%, respectively, with a cutoff value of 8.0 pg/mL. In patients with IGCT, the CSF-PLAP value was higher in patients with germinoma than in those with nongerminomatous germ cell tumors (n = 12 vs. 7; median: 415.0 vs. 359.0 pg/mL). Regarding the time course, the CSF-PLAP value decreased to below the detection limit after the reception of first-line chemoradiotherapy in all 7 patients. A significant correlation was observed between the initial CSF-PLAP value and the tumor reduction volume after receiving first-line chemoradiotherapy (p < 0.0003, R2 = 0.6165, logY = 1.202logX - 1.727). Among the patients with suspected IGCT recurrence (n = 6), the CSF-PLAP value was high in patients with recurrence (n = 3; median: 259.0 pg/mL), and that in patients (n = 3) without recurrence was below the lower detection limit. CONCLUSIONS: The CSF-PLAP level is a useful biomarker during the initial diagnosis of IGCTs and at the time of recurrence. It may be associated with the volume of germinomatous components of tumors.

Placental alkaline phosphatase in cerebrospinal fluid as a biomarker for optimizing surgical treatment strategies for pineal region germ cell tumors.

Pineal region germ cell tumors are a heterogenous group of tumors; of these, pure germinoma shows high sensitivity to adjuvant therapy, and the timing and sequence of surgical intervention and adjuvant/neoadjuvant therapy are important for devising a treatment strategy for intracranial germ cell tumors (IGCT). Biopsy is diagnostically useful, but is often insufficient because only a limited amount of specimen can be obtained. In the present study, we aimed to determine the value of cerebrospinal fluid placental alkaline phosphatase (PLAP) levels, reflecting the presence of germinoma, as a reliable indicator to determine treatment strategies for pineal germ cell tumors. To assess the relationship between elevated PLAP levels and the presence of germinoma, we retrospectively reviewed histopathological findings of 25 surgical cases of IGCT in the pineal region. The PLAP value reflects the existence of a germinoma component within a total tumor volume; consequently, tumor volume could be reduced in cases with elevated PLAP, while tumors negative for PLAP did not decrease in size. Therefore, PLAP levels may help neurosurgeons optimize surgical intervention timing for teratomas in the pineal region.

Placental alkaline phosphatase levels in cerebrospinal fluid can have a decisive role in the differential diagnosis of intracranial germ cell tumors.

OBJECTIVE: Placental alkaline phosphatase (PLAP) in CSF can provide a very high diagnostic value in cases of intracranial germ cell tumors (GCTs), especially in pure germinomas, to the level of not requiring histological confirmation. Unlike other tumor markers, reliable data analysis with respect to the diagnostic value of PLAP serum or CSF levels has not been available until now. This is the first systematic and comprehensive study examining the diagnostic value of CSF PLAP in patients with intracranial GCTs. METHODS: From 2004 to 2014, 74 patients (average age 19.6 ± 10.6 years) with intracranial GCTs were evaluated using PLAP from their CSF and histological samples. Chemiluminescent enzyme immunoassay was utilized to measure CSF PLAP in the following tumor sites: pineal (n = 32), pituitary stalk, suprasellar (n = 16), basal ganglia (n = 15), intraventricular (n = 9), and cerebellar (n = 5) regions. In addition to classifying GCT cases, all patients underwent tumor biopsy for correlation with tumor marker data. RESULTS: PLAP in combination with other tumor markers resulted in extremely high sensitivity and specificity of the diagnostic value of intracranial GCTs. Intracranial GCT cases were classified into 1) germinomas, both "pure" and syncytiotrophoblastic giant cell types (n = 38); 2) nongerminomatous GCTs, choriocarcinomas (n = 9) and teratomas (n = 4); and 3) nongerminomas, other kinds of tumors (n = 23). Consequently, all patients received chemoradiation therapy based on elevation of PLAP and the histopathological results. It was also speculated that the level of PLAP could show the amount of intracranial germ cell components of a GCT. PLAP was 100% upregulated in all intracranial germinoma cases. The absence of CSF PLAP proved that the tumor was not a germinoma. CONCLUSIONS: The current study is the first systematic and comprehensive examination of the diagnostic value of the tumor marker PLAP in pediatric patients with intracranial GCT. Using the level of PLAP in CSF, we were able to detect the instances of intracranial germinoma with very high reliability, equivalent to a pathological diagnosis.

Reference intervals for the activity of lactate dehydrogenase and its isoenzymes in the serum and cerebrospinal fluid of healthy canines.

BACKGROUND: Lactate dehydrogenase (LD) exists as 5 isoenzymes (LD-1 through LD-5) that are expressed throughout the body and can be detected in both serum and cerebrospinal fluid (CSF). LD and its isoenzymes have been relatively unstudied in veterinary medicine, although studies in human medicine have demonstrated that changes in total LD activity and atypical isoenzyme patterns can indicate disease processes, including neurologic abnormalities. OBJECTIVES: The purpose of this study was to establish RIs for LD and its isoenzymes in the serum and CSF of clinically healthy dogs. By establishing a definitive RI for this enzyme in healthy canines, further study of the clinical and diagnostic usefulness of LD can be undertaken. METHODS: Serum and atlantoaxial CSF were collected from clinically healthy dogs. Total LD activity was measured spectrophotometrically immediately after collection. Isoenzyme distributions were also determined within 8 hours of collection using the QuickGel LD Isoenzyme technique and a densitometric scanner. RESULTS: The median serum total LD in healthy canines was 69.0 U/L (n = 41; range: 21.0-217.0 U/L), while the median CSF total LD was 10.0 U/L (n = 40; range: 6.0-19.3 U/L). LD-5 is the predominant isoenzyme in canine serum (n = 40), contributing over half of the total enzyme activity. Conversely, in canine CSF (n = 42), LD-1 is the predominant isoenzyme, followed by LD-2 and LD-3. CONCLUSIONS: Knowledge of the distribution and concentration of LD in the serum and CSF of healthy dogs will set the foundation for future studies of canine LD as a potentially clinically useful biomarker.

A highly sensitive and specific chemiluminescent enzyme immunoassay for placental alkaline phosphatase in the cerebrospinal fluid of patients with intracranial germinomas.

BACKGROUND: Placental alkaline phosphatase (PLAP) in cerebrospinal fluid (CSF) has been proposed as a tumor marker for intracranial germinomas. The purpose of the present study was to develop a sensitive assay for measuring CSF PLAP and to evaluate the clinical significance of PLAP in patients with germinomas. METHODS: A chemiluminescent enzyme assay for PLAP was developed using an anti-human-PLAP monoclonal antibody. PLAP concentrations were determined in 37 controls, 36 germinomas, 3 nongerminomatous germ cell tumors, 21 gliomas and 12 other brain tumors. RESULTS: The assay detection limit was 5 pg/ml. The median PLAP concentration in the control group was below the detection limit. Significantly higher PLAP levels were detected in all 36 germinoma patients, with values ranging from 16 to 3,700 pg/ml. The high PLAP concentrations of 17 germinoma patients decreased to below the detection limit after complete remission had been achieved with radiochemotherapy. The sensitivity and specificity of PLAP for germinomas were 94 and 97%, respectively, with a cutoff value of 30 pg/ml. CONCLUSIONS: The results of this study suggest that the determination of CSF PLAP by the chemiluminescent method described here provides a clinically useful tumor marker for the diagnosis and monitoring of intracranial germinomas.

Pattern of cerebrospinal fluid lactic dehydrogenase during treatment of bacterial meningitis.

Bacterial and aseptic meningitis are characterized by distinctive lactic dehydrogenase isoenzyme patterns. No studies have quantified the dynamics of lactic dehydrogenase isoenzyme distribution during treated bacterial meningitis. We used a retrospective case-series design, and reviewed files of all neonates with bacterial meningitis who attended our pediatric tertiary medical center for 8 years period. We identified neonates in whom a repeated lumbar puncture was indicated. Findings of cerebrospinal fluid analysis, including levels of lactic dehydrogenase isoenzymes, were compared with an age-matched reference group. In two patients with meningitis, lumbar puncture with cerebrospinal fluid analysis was repeated because of inadequate response to treatment or initially obscure etiologic pathogens. Both patients had initially low levels of lactic dehydrogenase-1 and lactic dehydrogenase-2 and high levels of lactic dehydrogenase-4 and lactic dehydrogenase-5, similar to other patients with bacterial meningitis. The distribution pattern of lactic dehydrogenase isoenzyme normalized after adequate antibiotic treatment. In light of the encouraging results in these two patients, further studies are warranted regarding the value of lactic dehydrogenase isoenzyme measurements for follow-up purposes and for evaluations of response to treatment.

Lactic dehydrogenase isoenzymes in adolescents with multiple sclerosis.

Multiple sclerosis is an immune-mediated demyelinating disease with high morbidity and major mortality. To determine the potential use of lactic dehydrogenase activity and lactic dehydrogenase isoenzyme concentrations in cerebrospinal fluid as biomarkers of multiple sclerosis, we reviewed the files of all patients with multiple sclerosis who attended our tertiary pediatric medical facility from 1999-2005. The study group included three adolescent patients with multiple sclerosis (cerebrospinal fluid analysis at diagnosis) and one patient with recurrent optic neuritis (cerebrospinal fluid analysis during a disease episode). The isoenzyme pattern was abnormal in all patients with multiple sclerosis, with higher-than-normal levels of lactic dehydrogenase-2, lactic dehydrogenase-3, and lactic dehydrogenase-5 in two patients, and lower-than-normal levels of lactic dehydrogenase-4 in one patient. It was not necessarily, however, the same two patients who had the abnormally high levels of lactic dehydrogenase-2, -3, and -5. The patient with optic neuritis also exhibited an abnormal lactic dehydrogenase isoenzyme pattern that shared common features with the others. Multiple sclerosis appears to be characterized by an abnormal lactic dehydrogenase isoenzyme pattern in cerebrospinal fluid. The importance of this finding and its diagnostic potential use warrant further investigation.

Cerebrospinal fluid lactate dehydrogenase isoenzymes in children with bacterial and aseptic meningitis.

Differentiation of bacterial from aseptic meningitis may be difficult. Our aim was to determine the pattern of distribution of lactate dehydrogenase (LDH) isoenzymes in the cerebrospinal fluid (CSF) of patients with bacterial and aseptic meningitis. One hundred and fifty-seven patients with suspected meningitis were enrolled in the study. They were divided into 3 groups according to the culture- or bacterial antigen assay-proven diagnosis and CSF findings: bacterial meningitis (n = 31), aseptic meningitis (n = 65), and non-meningitis (n = 61). Total LDH level and percentages of LDH isoenzymes in the CSF were measured in each patient. Each group showed a distinct LDH isoenzyme distribution pattern, with a statistically significant difference among the groups in the percentages of the various isoenzymes. Compared with the non-meningitis group, total LDH activity in the CSF was high in the aseptic meningitis group (49.82+/-35.59 U/L, P < 0.001) and exaggerated in the bacterial meningitis group (944.53+/-112.3 U/L, P < 0.001). Low LDH-2 levels were unique to bacterial meningitis (P < 0.01), whereas high LDH-3 levels were characteristic of aseptic meningitis (P < 0.05). Both groups had low levels of LDH-1 and high levels of LDH-4 and LDH-5. In conclusion, the LDH isoenzyme pattern may be of clinical diagnostic value in meningitis, particularly when culture results are pending.

[Study of lactate dehydrogenase isoenzyme in the cerebrospinal fluid of patients with acute lymphoblastic leukemia].

Lactate dehydrogenase isoenzymes were profiled in cerebrospinal fluid in patients with acute lymphoblastic leukemia. Cytological examination of patients with central nervous involvement identified isoenzyme 5 which failed to show after selective treatment. The isoenzyme's detection in cerebrospinal fluid without typical cytological characteristics may be regarded as a precursor of such complication. Hence, this may be used as an additional criterion for refinement of cytological evidence employed in diagnosis and prognosis of central nervous involvement in patients with acute lymphoblastic leukemia.

Increased expression of intracystic matrix metalloproteinases in brain tumors: relationship to the pathogenesis of brain tumor-associated cysts and peritumoral edema.

Although several types of brain tumors are commonly associated with cyst formation, the pathogenesis of tumor-associated cysts (TAC) is unknown. We investigated the matrix metalloproteinase (MMP) expression of cyst fluids to elucidate the pathogenesis of TAC in brain tumors. We also examined the relationship between the severity of peritumoral edema and the expression of intracystic MMP. We collected 40 cyst fluid samples from 34 patients with TAC and studied the expression of MMP-2 and -9 in the cyst fluid using gelatin zymography. Radiological studies were used to estimate the severity of the peritumoral edema and to determine the presence of TAC. Although gelatin zymography of the cyst fluid showed high levels of MMPs, there was no correlation between the expression of MMPs in the cyst fluid and that in the tumor tissue. The level of MMP expression in the cyst fluid did not reflect the pathologic grade of the individual tumors. However, the total and activated MMP-9 levels were significantly associated with the severity of the peritumoral edema (p<0.05). These results suggest that MMPs may be partly involved in the pathogenesis of TAC and peritumoral edema in brain tumors.

Adenylate kinase 5 autoimmunity in treatment refractory limbic encephalitis.

We report two men with limbic encephalitis (LE) refractory to corticosteroids, IVIg and plasma exchange. Both patients had serum/CSF antibodies that reacted with the cytoplasm of neurons. Probing of a hippocampal cDNA library resulted in the isolation of adenylate kinase 5 (AK5). Patients' antibodies, but not those of 111 controls, recognized AK5-expressing phage plaques. Human AK5-affinity purified antibodies reproduced the neuronal immunolabeling of patients' antibodies, and co-localized with a rabbit AK5 antibody, confirming that the brain autoantigen was AK5. Detection of antibodies to AK5 in LE patients carries a poor prognosis, and suggests the prompt use of aggressive immunosuppression.

Prostaglandin D synthase isoforms from cerebrospinal fluid vary with brain pathology.

Glutathione independent prostaglandin D synthase (Swissprot P41222, PTGDS) has been identified in human cerebrospinal fluid and some changes in PTGDS in relation to disease have been reported. However, little is known of the extent that PTGDS isoforms fluctuate across a large range of congenital and acquired diseases. The purpose of this study was to examine changes in PTGDS isoforms in such a population. Spinal fluid from 22 healthy study participants (normal controls) with no classifiable neurological or psychiatric diagnosis was obtained and PTGDS isoforms were identified by specific immunostaining and mass spectrometry after denaturing 2D gel electrophoresis. The PTGDS isoforms in controls consisted of five charge isoforms that were always present and a small number of occasional, low abundance isoforms. A qualitative survey of 98 different people with a wide range of congenital and acquired diseases revealed striking changes. Loss of the control isoforms occurred in congenital malformations of the nervous system. Gain of additional isoforms occurred in some degenerative, most demyelinating and vasculitic diseases, as well as in Creutzfeldt-Jakob disease. A retrospective analysis of published data that quantified relative amounts of PTGDS in multiple sclerosis, schizophrenia and Parkinson's disease compared to controls revealed significant dysregulation. It is concluded that qualitative and quantitative fluctuations of cerebrospinal fluid PTGDS isoforms reflect both major and subtle brain pathophysiology.

Improved confidence intervals for the sensitivity at a fixed level of specificity of a continuous-scale diagnostic test.

For a continuous-scale diagnostic test, it is of interest to construct a confidence interval for the sensitivity of the diagnostic test at the cut-off that yields a predetermined level of its specificity (for example, 80, 90 or 95 per cent). In this paper we propose two new intervals for the sensitivity of a continuous-scale diagnostic test at a fixed level of specificity. We then conduct simulation studies to compare the relative performance of these two intervals with the best existing BCa bootstrap interval, proposed by Platt et al. Our simulation results show that the newly proposed intervals are better than the BCa bootstrap interval in terms of coverage accuracy and interval length.

Long-lasting acetylcholinesterase splice variations in anticholinesterase-treated Alzheimer's disease patients.

Protein levels of different acetylcholinesterase (AChE) splice variants were explored by a combination of immunoblot techniques, using two different antibodies, directed against the C-terminus of the AChE-R splice variant or the core domain common to all variants. Both AChE-R and AChE-S splice variants as well as several heavier AChE complexes were detected in brain homogenates from the parietal cortex of patients with or without Alzheimer's disease (AD) as well as the cerebrospinal fluid (CSF) of AD patients, compatible with the assumption that CSF AChEs might originate from CNS neurons. Long-term changes in the composition of CSF AChE variants were further pursued in AD patients treated with rivastigmine (n = 11) or tacrine (n = 17) in comparison to untreated AD patients (n = 5). In untreated patients, AChE-R was markedly reduced as compared with the baseline level (37%), whereas the medium size AChE-S complex was increased by 32%. Intriguingly, tacrine produced a general and profound up-regulation of all detected AChE variants (up to 117%), whereas rivastigmine treatment caused a mild and selective up-regulation of AChE-R ( approximately 10%, p < 0.05). Moreover, the change in the ratio of AChE-R to AChE-S (R/S-ratio) strongly and positively correlated with sustained cognition at 12 months (p < 0.0001). Thus, evaluation of changes in the composition of CSF AChE variants may yield important information referring to the therapeutic efficacy and/or development of drug tolerance in AD patients treated with anti-cholinesterases.

CSF lactate dehydrogenase activity in patients with Creutzfeldt-Jakob disease exceeds that in other dementias.

The diagnosis of Creutzfeldt-Jakob disease (CJD) is still made by exclusion of other dementias. We now evaluated lactate dehydrogenase (LDH) in the cerebrospinal fluid (CSF) as a possible additional diagnostic tool. CSF LDH levels of patients with CJD (n = 26) were compared with those in other dementias (n = 28). LDH isoenzymes were determined in a subset (n = 9). Total LDH and isoenzyme LDH-1 were significantly higher, whereas the fractions of LDH-2 and LDH-3 were significantly lower in CJD patients. We conclude that in addition to established CSF parameters, LDH and its isoenzymes might serve as a further help to discriminate between CJD and other dementias.

Cyclo-oxygenases and prostaglandins in acute inflammatory demyelination of the peripheral nerve.

OBJECTIVE: To investigate the expression of cyclo-oxygenases (COX), key enzymes in propagating inflammatory responses by converting arachidonic acid to prostaglandins, in inflammatory demyelinating disorders of the peripheral nervous system (PNS). METHODS: Expression and distribution of COX messenger RNA (mRNA) and protein were studied in sural nerve biopsies, serum, and CSF samples from patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), or, for comparison, with vasculitic neuropathy (VN), which is a inflammatory nondemyelinating disorder, and noninflammatory neuropathies (NIN) using RT-PCR, immunohistochemistry, and immunoblotting. To confirm functional COX-2 activity, the expression of prostaglandin E(2) (PGE(2)) and prostaglandin F(2alpha) (PGF(2alpha)) was evaluated by ELISA ex vivo and in vitro. RESULTS: Whereas COX-1 expression was unaltered in all investigated groups, a significant upregulation of COX-2 mRNA was detected in sural nerves from patients with GBS, CIDP, or VN but not in control subjects with noninflammatory disorders. Macrophages were identified as its primary cellular source. Increased COX-2 protein levels were detectable in serum and CSF from all patients with GBS and, in smaller numbers only, in samples from patients with CIDP or VN but not from the NIN group studied. Moreover, increased levels of PGE(2) and PGF(2alpha) were measurable in sera from patients with GBS, CIDP, or VN and in cell culture supernatants from in vitro stimulated macrophages, indicative of COX-2 activity. CONCLUSIONS: Cyclo-oxygenase-2, expressed by macrophages, may generate prostaglandins during acute inflammatory demyelination of the peripheral nerve.

Detection and characterization of 45 kDa platelet activating factor acetylhydrolase in cerebrospinal fluid of children with meningitis.

Platelet activating factor acetylhydrolase (PAF-AH) activity has been identified in cerebrospinal fluid (CSF) samples taken from children with meningitis. We reported that PAF-AH activity is significantly increased, by about 3 fold, in patients with meningitis compared to control subjects. Because of limited knowledge about this enzyme in CSF, we examined the biochemical properties of CSF PAF-AH. PAF-AH of CSF was calcium independent, showed a broad pH spectrum and was relatively heat stable. In addition, this enzyme activity was strongly inhibited by phenylmethanesulfonyl fluoride (PMSF), partially inhibited by p-bromophenacylbromide (p-BPB), uninhibited by iodoacetamide, and moderately stimulated by dithiothreitol (DTT). PAF-AH of CSF did not degrade phospholipid with a long chain fatty acyl group at sn-2 position. This enzyme hydrolyzed PAF and oxidatively modified phosphatidylcholine. Furthermore, we identified a monomeric polypeptide with a molecular weight of approximately 45 kDa by Western blot using human plasma PAF-AH antibody. These results suggested that plasma type PAF-AH activity exist in CSF taken from children with meningitis.

Lactic dehydrogenase isoenzyme in cerebrospinal fluid of children with infantile spasms.

Increased levels of lactic dehydrogenase (LDH) in cerebrospinal fluid (CSF) have been reported in association with several intracranial pathologies. We studied LDH isoenzymes in the CSF of children with infantile spasms. CSF samples collected from 12 patients (aged 4-9 months) with infantile spasms were analyzed for total LDH isoenzymes activity, and were compared to samples from 15 normal children. Mean total LDH activity in the CSF was 34.62 +/- 6.52 U/l. Patients with infantile spasms had a lower LDH-1 percentage and higher LDH-3 percentage; the differences from the control group were statistically significant (p < 0.01). LDH-4 and LDH-5 had similar values in both groups. Infantile spasm is apparently associated with a distinct LDH isoenzyme pattern in the CSF. More studies are needed to confirm the rise in LDH-2, LDH-3 and to determine the optimum time of analysis.

Lactic dehydrogenase isoenzyme in cerebrospinal fluid of children with febrile convulsions.

AIM: To study the lactic dehydrogenase isoenzyme values in children with simple and complex febrile convulsions. METHODS: Cerebrospinal fluid samples were collected from 115 children, 57 with simple febrile convulsions, 27 with complex febrile convulsions and 31 with no neurological or intracranial pathology (controls). Lactic dehydrogenase activity and isoenzyme levels were measured on a Hitachi analyser. RESULTS: Mean total lactic dehydrogenase activity was similar in the three groups. In the control group, lactic dehydrogenase-1 was the main fraction, followed by lactic dehydrogenase-2 and lactic dehydrogenase-3; only small percentages of lactic dehydrogenase-4 and lactic dehydrogenase-5 were detected. In the febrile convulsion group, the lactic dehydrogenase-1 fraction percentage was lower and lactic dehydrogenase-2, lactic dehydrogenase-3 percentages were higher than those in the control group; and the differences were statistically significant between the control and study groups (p < 0.01). Values of lactic dehydrogenase-4 and lactic dehydrogenase-5 were similar in all three groups. CONCLUSION: This is the first report on the lactic dehydrogenase isoenzyme pattern in the cerebrospinal fluid of patients with simple and complex febrile convulsions. The important finding that focal and general febrile convulsions are not associated with cell damage and changes in aerobic and anaerobic metabolism as lactic dehydrogenase remained unchanged. Analysis of cerebrospinal fluid lactic dehydrogenase isoenzyme levels can assist clinicians in differentiating febrile convulsions from clinical situations that might mimic them.