Serum and CSF neuron-specific enolase in patients with West syndrome

OBJECTIVE: To determine whether frequent seizures and/or hypsarrhythmia may cause neuronal injury in West syndrome. BACKGROUND: West syndrome is an age-related epileptic syndrome of infancy characterized by clusters of epileptic spasms, a peculiar interictal EEG pattern of hypsarrhythmia, and mental deterioration. Recent clinical studies demonstrated that serum and CSF neuron-specific enolase (NSE)-a marker of neuronal injury-were increased after status epilepticus. METHODS: The authors examined serum and CSF NSE levels in 18 newly diagnosed infants (8.4 +/- 2.2 months) with West syndrome (3 cryptogenic, 15 symptomatic). In patients who showed complete resolution of spasms and disappearance of hypsarrhythmia (responders), additional serum NSE levels were determined several weeks after cessation of seizures. Serum NSE levels were obtained from 28 age-matched infants with normal neurologic development (control group), and 10 infants with an acute neurologic insult. RESULTS: There were no significant differences (p > 0.05) in serum NSE levels between the group with West syndrome (12.9 +/- 3.4 ng/mL) and the control group (13.2 +/- 3.1 ng/mL). The serum NSE value in the group with an acute insult (100.3 +/- 67.4 ng/mL) was significantly higher (p < 0.0001) than that for the West syndrome and the control groups. The mean +/- SD CSF NSE level was 7.3 +/- 3.6 ng/mL, which is similar to the reported CSF NSE levels of Japanese infants without neurologic disease. Thirteen responders showed no significant (p > 0.05) change in serum NSE after cessation of epileptic spasms. CONCLUSION: Normal serum and CSF neuron-specific enolase levels provided no evidence that seizures and/or hypsarrhythmia induced neuronal injury in West syndrome.     

Erythropoietin in the cerebrospinal fluid of patients with aneurysmal subarachnoid haemorrhage originates from the brain

Recent years' research has revealed a specific, neuroprotective erythropoietin (EPO) system in the central nervous system (CNS) that is upregulated by hypoxia. The presence and dynamics of EPO in the cerebrospinal fluid (CSF) of patients with subarachnoid haemorrhage (SAH) has not been investigated. We collected a total of 83 corresponding serum and CSF samples from 18 patients with aneurysmal SAH and compared the concentrations of EPO with those of blood-derived markers of blood-brain barrier function (albumin, transferrin, alpha(2)-macroglobulin) and with those of proteins with well-known CNS synthesis (prealbumin, apolipoprotein E). The EPO concentration in CSF was 0.93 (0.82) mU/ml (median and inter-quartile range). Nine patients presented CSF-EPO values above 1 mU/ml. CSF levels did not correlate with serum concentrations and were independent of blood-brain barrier integrity suggesting a synthesis in CNS rather than a blood-derived origin. Furthermore, the median CSF:serum ratio (Q(protein)) of EPO was similar to those of prealbumin and apolipoprotein E, and much higher than those of albumin, transferrin and alpha(2)-macroglobulin. When the Q(protein) of all proteins were plotted against Q(albumin), EPO showed dynamics similar to CNS-derived proteins. Our data indicate that EPO in the CSF of patients with aneurysmal SAH originates mainly from the CNS.     

Cerebrospinal Fluid and Serum Neuron-Specific Enolase Levels After Febrile Seizures

PURPOSE: Neuron-specific enolase (NSE) has been established as a reliable marker of neuronal damage in various neurologic disorders. The aim of this study was to evaluate whether febrile seizures (FS) cause brain damage, based on the serum and cerebrospinal fluid (CSF) levels of NSE. METHODS: Fifty-three patients aged from 6 months to 7 years were enrolled. Among them, 36 patients had generalized seizures, and 17 had partial seizures. The maximal seizure duration was 90 min. Blood and CSF samples for measurement of NSE were obtained immediately after the seizure. NSE was measured using an enzyme immunoassay (EIA). RESULTS: Serum and CSF levels of NSE ranged up to 10 ng/mL, but very high levels were not observed. In patients with partial seizures, the NSE level in the CSF and the ratio of the CSF to serum NSE levels showed a strong correlation with seizure duration. Conversely, there were no correlations between NSE levels and seizure duration in the patients with generalized seizures. CONCLUSIONS: These results indicate that FS seldom cause severe neurologic damage, but prolonged partial seizures may cause slight neuronal injury.     

Lack of neuronal damage in atypical absence status epilepticus

PURPOSE: Whether status epilepticus of nonconvulsive epileptic seizures is harmful still remains controversial. To investigate this, the presence and/or extent of neuronal damage in patients with absence status epilepticus (ASE) and patients with complex partial status epilepticus (CPSE) was examined and compared. METHODS: Neuron-specific enolase (NSE) in CSF was examined in the patients with ASE and compared with that of the patients having CPSE. Clinical aspects of these patients also were investigated. RESULTS: CSF NSE levels in ASE patients were lower than those of CPSE patients and were considered as the normal values. No clinical symptoms indicated neuronal damage in the ASE patients. CONCLUSIONS: This study suggests that ASE does not induce neuronal damage. Serum NSE is not always correlated to CSF NSE, and determination of serum NSE levels may be an inappropriate method of estimating neuronal damage in some cases of ASE.     

癫痫患者血清和脑脊液神经元特异性烯醇化酶的测定

目的 探讨癫痫发作对脑神经元的损伤。方法 应用酶联免疫反应法动态测定癫痫发作后患者血清和脑脊液（CSF）中神经元特异性烯醇化酶（NSE）的含量。结果 癫痫组血清和CSF中NSE含量在发作后明显升高，血清NSE水平在发作后第1天最高，1周左右开始下降，2周左右降至正常；抽搐发作及频繁发作时，血清和CSF中NSE升高更明显。结论 癫痫发作引起血清和CSF中NSE水平的升高；癫痫发作导致神经元损伤，抽搐发作及频繁发作时神经元损伤更严重。     

Isolated blood–cerebrospinal fluid barrier dysfunction: prevalence and associated diseases

OBJECTIVE : An isolated dysfunction of the blood-CSF barrier is characterised by an abnormal elevation of the albumin CSF/serum concentration ratio (Q(alb)) without any other pathological CSF findings. Although common in routine CSF analysis, the clinical significance of an isolated barrier dysfunction frequently remains unclear. We examined neurological disorders associated with an isolated elevation of Q(alb) to identify possible determinants of blood-CSF barrier dysfunction. METHODS : 367 patients (124 women, 243 men, median age 60. 0 years) out of 3,873 patients receiving diagnostic lumbar puncture at the University Hospital of Ulm (Germany) showed an isolated dysfunction of the blood-CSF barrier. Clinical data as well as MRI findings of these patients were analysed. RESULTS : Isolated barrier dysfunction occurred most frequently (> 30%) in Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), normal pressure hydrocephalus (NPH), lumbar spinal stenosis, and polyneuropathy (PNP). In patients who showed no other evidence of neurological disease, isolated barrier dysfunction was found in 14. 9% of cases. The extent of barrier dysfunction was most prominent in brain tumours, GBS, and CIDP. There was a significant correlation of Q(alb) with both weight and body mass index (BMI). CONCLUSIONS : Although isolated barrier dysfunction may be found in a variety of neurological diseases, it is especially frequent in GBS, CIDP, NPH, spinal canal stenosis, and PNP. In these patients, disease-related mechanisms contributing to barrier dysfunction are likely. Moreover, barrier function seems to be influenced by disease-independent determinants like weight and BMI.     

The relationship between levels of cerebrospinal fluid myelin basic protein and IgG measurements in patients with multiple sclerosis

Cerebrospinal fluid (CSF) myelin basic protein (MBP) levels, CSF/serum albumin ratio (CSF/S alb), and 4 CSF IgG measurements--absolute CSF IgG level (CSF IgG), CSF IgG/albumin ratio, the Tibbling-Link IgG index, and the daily rate of intrathecal IgG synthesis--were measured in patients with multiple sclerosis and control subjects. In four clinical subgroups of patients, including 22 with polysymptomatic exacerbations, 22 with monosymptomatic exacerbations, 41 with chronic progressive disease, and 21 in remission, there was no correlation between CSF MBP and either CSF/S alb or the CSF IgG measurements. This finding was also observed in longitudinal studies of patients. CSF MBP levels, as determined in a cross-sectional study of 325 patients with multiple sclerosis, are an excellent indicator of disease activity.     

运动神经元病患者血清和脑脊液中NSE和GM1抗体测定及其临床意义

目的　通过测定运动神经元病(MND)患者血清和脑脊液(CSF)中神经元特异性烯醇化酶(NSE)和GM1抗体,初步探讨其临床意义。方法　应用ELISA法测定30例MND患者血清和CSF中NSE和GM1抗体水平。结果　MND组CSF和血清中NSE含量均明显高于NC组(P<0.01,P<0.05),而仅在CSF中NSE含量高于OND组(P<0.01);临床分型以运动神经元损害为主的进行性脊肌萎缩症(PSMA)患者CSF中NSE含量明显高于其他组(P<0.01),而血清中NSE水平在各临床类型间差异并不明显(P>0.05);MND患者血清和CSF中不论是IgM型或是IgG型GM1抗体阳性率均明显高于OND组和NC组(P均<0.01);MND患者血清和CSF配对样品NSE水平有较好的相关性(r=0.502,P<0.01),MND患者CSF中NSE水平与GM1抗体亦有相关性(r=0.475,P<0.05),其余各组之间均未见明显相关性(P>0.05)。结论　MND患者CSF中NSE和GM1抗体水平可以反映运动系统神经元损害的程度和范围;推测这种神经元的损伤可能与GM1抗体介导的中枢神经系统免疫反应有关。     

Normal CSF neuron-specific enolase and S-100 protein levels in patients with recent non-complicated tonic-clonic seizures

PURPOSE: Increased concentrations of the nervous-system-specific proteins neuron-specific enolase (NSE) and S-100 protein (S-100) have been measured with lesions in the CNS. Elevated levels of serum NSE (s-NSE) have been found in status epilepticus, but also after single epileptic seizures. Because larger studies addressing cerebrospinal fluid (CSF) levels of NSE or S-100 have not been performed, we measured CSF NSE and S-100 after tonic-clonic seizures to search for evidence of neuronal and glial damage. METHODS: 22 consecutive patients with single, previously undiagnosed and untreated tonic-clonic seizures were studied. Serum and CSF samples were collected within 24 h after seizure. 18 serum and CSF samples were measured from a control group. RESULTS: The mean CSF NSE was 8.9 ng/ml (range 0-28 ng/ml) and s-NSE 8.2 ng/ml (range 5-15 ng/ml) in the patient group. The mean concentrations in the control group were 13.1 ng/ml (range 3-24 ng/ml) and 8.0 ng/ml (range 5-12 ng/ml) respectively. The mean CSF S-100 was 3.17 microg/l (range 1.45-7.02 microg/l) and serum S-100 0.05 microg/l (range 0-0.32 microg/l), and in controls 3.19 microg/l (range 1.52-5.13 microg/l) and 0.08 microg/l (range 0-0.28 microg/l). CONCLUSION: There were no significant differences between the mean concentrations of NSE or S-100 in CSF and serum between the epileptic group and controls. These results do not confirm the previous observation of elevated NSE-levels after tonic-clonic seizures, which argues against neuronal or glial damage after uncomplicated tonic-clonic seizures in unmedicated patients.     

Relevance of immunological variables in neuroborreliosis and multiple sclerosis

OBJECTIVES: The aims were to investigate the frequency of intrathecal synthesis of specific antibodies against measles (M), rubella (R) and varicella zoster (Z) viruses (MRZ reaction) as a diagnostic marker between multiple sclerosis (MS) and neuroborreliosis (NB) groups and to postulate the most typical cerebrospinal fluid (CSF) variables profile of these entities. METHODS: Three cohorts of patients were investigated: MS (n = 42), NB (n = 27) and other neurological diseases (OND) (n = 15). Measles, rubella, varicella zoster and borrelia-specific IgG antibodies were measured by ELISA, Q(alb) (CSF/serum albumin ratio) as a marker of blood-CSF barrier function and specific antibody indices (AI) were calculated according to relevant formulae. IgG oligoclonal bands (OB) were detected by isoelectric focusing and immunoenzymatic staining. RESULTS: Eighty-eight percent of MS patients had positive MRZ reaction and 26.2% had positive anti-borrelia AI. Eighty-nine percent of NB patients had positive anti-borrelia AI and two patients had individually anti-measles and rubella positive AI. MS-CSF variables profile included the presence of IgG OB in 81%, elevated Q(alb) in 31% and normal cell count in 66.7%. Of NB patients IgG OB were positive in 74%, elevated Q(alb) in 81.5% and normal cell count in 7.4%. CONCLUSION: MRZ reaction was proved as statistically significant marker in differential diagnosis between MS and NB. Typical CSF variables profile of these two entities is highly supportive, especially when MRZ is included.