Cerebrospinal fluid zinc concentrations in febrile convulsions

Zinc modulates the activity of glutamic acid decarboxylase, the rate limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. Low cerebrospinal fluid GABA values have been reported in association with several seizure disorders, including febrile convulsions. It is also known that fever and/or infections may cause a reduction in serum zinc concentrations. In this study the hypothesis that febrile convulsions are related to low cerebrospinal fluid zinc was tested. Cerebrospinal fluid zinc concentrations were measured in 66 febrile children: 32 with febrile convulsions, 18 with fever but without convulsions, and 16 with aseptic (viral) meningitis. There was no statistically significant difference in the cerebrospinal fluid zinc between the three groups of children, and the mean concentration was 26.2 micrograms/l. No significant relationship was found between either age, gender, maximal temperature, type of infection, or time of performance of the lumbar puncture and cerebrospinal fluid zinc concentration. These results do not support the hypothesis that febrile convulsions are related to reduced cerebrospinal fluid zinc concentrations.     

Gamma-Aminobutyric Acid Concentration in Lumbar Cerebrospinal Fluid from Patients with Febrile Convulsions and Controls

ABSTRACT. The cerebrospinal fluid (CSF) concentration of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) was analysed in 41 children with febrile convulsions (FC), 41 febrile controls of similar age (control group 1), and 59 controls, who had no fever and/or were outside the age range for FC (control group 2). A significant correlation between CSF-GABA and age was demonstrated for controls (1 + 2) (r= 0.63, p < 0.00001), as well as for patients with FC (r= 0.42, p= 0.003). Patients with FC did not differ significantly from control group 1 in respect to CSF-GABA. Duration of FC was related to both CSF-GABA and age (GABA: r=−0.29, p < 0.05; age: r =−0.32, p < 0.05). For 56 controls (1 + 2) > 1 year of age, a significant negative correlation between CFC-GABA and body temperature was found (r=−0.34, p = 0.01). The low CSF-GABA in the FC-labile age group, the negative correlation of CSF-GABA to body temperature, and the negative correlation of the duration of FC to both CSF-GABA and age, all indicate that GABA could be of importance in the pathophysiology of FC.     

Gamma-aminobutyric acid concentration in lumbar cerebrospinal fluid from patients with febrile convulsions and controls

The cerebrospinal fluid (CSF) concentration of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) was analysed in 41 children with febrile convulsions (FC), 41 febrile controls of similar age (control group 1), and 59 controls, who had no fever and/or were outside the age range for FC (control group 2). A significant correlation between CSF-GABA and age was demonstrated for controls (1 + 2) (r = 0.63, p less than 0.00001), as well as for patients with FC (r = 0.42, p = 0.003). Patients with FC did not differ significantly from control group 1 in respect to CSF-GABA. Duration of FC was related to both CSF-GABA and age (GABA: r = -0.29, p less than 0.05; age: r = -0.32, p less than 0.05). For 56 controls (1 + 2) greater than 1 year of age, a significant negative correlation between CFC-GABA and body temperature was found (r = -0.34, p = 0.01). The low CSF-GABA in the FC-labile age group, the negative correlation of CSF-GABA to body temperature, and the negative correlation of the duration of FC to both CSF-GABA and age, all indicate that GABA could be of importance in the pathophysiology of FC.     

The role of fever on cerebrospinal fluid glucose concentration of children with and without convulsions

In febrile convulsions glucose concentrations are known to increase both in the blood and cerebrospinal fluid (CSF). The reason behind this increase is, however, incompletely understood. We have studied the effects of convulsion and fever on the CSF and blood glucose concentrations in four different groups of children: febrile and non-febrile children, with and without convulsions. The concentration of glucose in the CSF was significantly higher in febrile children with (4.4 ± 0.1 mmol/1, mean ± SEM n = 35, p < 0.01, ANOVA, Duncan's test) and without convulsions (3.9 ± 0.2mmol/1, n = 22, p < 0.05) than in non-febrile, non-convulsive children (3.3 ±0.1 mmol/1, n = 21). In non-febrile convulsive children, the CSF glucose concentration was 3.7 ± 0.2mmol/l (n = 10). Both fever and seizures increased the CSF glucose levels (p < 0.0001 and p = 0.028, respectively, analysis of covariance). There was a linear correlation between the body temperature and concentration of glucose in the CSF (r = 0.454, p < 0.0001, n = 88, Pearson's correlation analysis). The changes in blood glucose concentrations between the groups parallelled those found in the CSF. Our results show that hyperglycaemia and an increase in the CSF glucose concentration in febrile convulsions is not explained just by a stress reaction, evoked by the seizure, as has been hypothesized earlier, but by the influence of increased body temperature as well.     

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 3 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.     

Osmolality and electrolytes in cerebrospinal fluid and serum of febrile children with and without seizures

Abstract During acute febrile diseases mild disturbances of water and electrolyte balance occur frequently. It has been suggested that changes in electrolyte balance, in particular hyponatraemia, might predispose a child to convulsions during febrile illness; however, the changes of electrolytes in the CSF are not known.We have studied the effects of fever and convulsions on water and electrolyte balance in CSF and serum by measuring osmolality and electrolyte concentrations in children. The febrile population consisted of 60 children, 36 of whom had seizures during fever. Twenty-one children without convulsions and nine children with epileptic symptoms were nonfebrile controls. We noticed that CSF is subject to changes in osmolality and electrolyte concentration during fever, while convulsions do not exhibit such changes. CSF osmolality and sodium concentrations were lower in febrile children than in nonfebrile controls. The osmolality in febrile children with convulsions was 3.8% (P<0.01) and without seizures 3.5% (P<0.01) lower than in nonfebrile nonconvulsive children. The changes in CSF sodium concentration, and to a lesser extent potasium and chloride concentrations, paralleled those of CSF osmolality. A positive correlation was observed between the CSF and serum osmolatities (r=0.73,P<0.0001), and sodium concentrations (r=0.63,P<0.0001). A negative correlation between the body temperature and both CSF osmolality (r=–0.66,P<0.0001) and sodium concentration (r=–0.59,P<0.0001) exhibits also the important regulative role of increased body tmeperature.Conclusion Fever is an important factor for disturbances in fluid and electrolyte balance. The alterations in CSF osmolality and sodium concentration do not, however, give an unambiguous explanation for the susceptibility to simple febrile seizures.     

Taurine in the cerebrospinal fluid in febrile convulsions in children

Taurine may function in brain as a neuroinhibitor, and intracerebroventricular taurine has the capacity to induce hypothermia. Its antiepileptic properties have been observed in animals and humans. On the basis of these data, we studied taurine concentration in the cerebrospinal fluid of 32 children with simple febrile convulsions (16 +/- 6 months) and of 25 children with acute hyperthermia without neurologic signs (13 +/- 8 months). Taurine concentration in cerebrospinal fluid was similar in febrile convulsion children (8 +/- 4 mumol/l) compared to a control group (7.8 +/- 3 mumol/l).     

Plasma and cerebrospinal fluid arginine vasopressin in patients with and without fever.

Hyponatraemia has been described in association with a number of acute infectious diseases, mainly bacterial and tuberculous meningitis and pneumonia, and has been attributed to inappropriate secretion of arginine vasopressin (AVP). The mechanism of inappropriate AVP production is uncertain, but there is experimental evidence to suggest that fever may stimulate secretion of AVP into plasma and cerebrospinal fluid. In this study, AVP concentrations in plasma and cerebrospinal fluid from 37 febrile children with infections have been compared with those from 27 afebrile control subjects. Ten of the febrile children had meningitis (eight bacterial, two viral) and the remainder a variety of other infectious diseases. Seventy four per cent of febrile infected children were hyponatraemic (serum sodium less than 135 mmol/l) compared with only 8% of the afebrile controls. Plasma AVP concentrations were significantly higher in the febrile patients (median 2.92 pmol/l, range 1.0-23.25, n = 28) than in controls (median 1.67 pmol/l, range 0.57-6.0, n = 14) but there was no significant difference in cerebrospinal fluid AVP concentrations. There was no difference in plasma AVP concentrations between patients with meningitis and those with infections not involving the central nervous system. Careful attention should be paid to fluid and electrolyte balance in all children with acute infections.     

Seizures and fever: can we rule out meningitis on clinical grounds alone?

A study was done of 309 children seen in two ERs with a first seizure and fever to assess whether meningitis could be recognized using readily available clinical information. Among these children, 23 (7%) cases of meningitis were diagnosed. A group of 69 children with seizures and fever but no meningitis served as controls. Signs from ER examinations that discriminated between children with and those without meningitis were: petechiae, nuchal rigidity, coma, persistent drowsiness, ongoing convulsions, and paresis or paralysis; 21 cases were thus identified. Two children with a suspicious history but none of these signs proved to have meningitis. Children whose seizures showed no complex features and whose febrile illness revealed no suspicious features did not have meningitis. Our results indicate that based on available clinical data, meningitis can be ruled out in children presenting with seizures and fever; thus, there is no need for routine investigation of cerebrospinal fluid.     

Lower degree of fever at the initial febrile convulsion is associated with increased risk of subsequent convulsions.

We studied 132 children admitted consecutively with their first febrile convulsion to assess whether the degree of fever at the onset of the convulsion can predict the risk of subsequent convulsions. The children studied were reviewed at least 2 years after the initial febrile convulsion to determine the number of children who had recurrences of febrile convulsions and/or afebrile convulsions. Children with body temperatures below 39 degrees C at the onset of their initial febrile convulsion (Group 1) were two and half times more likely to experience multiple convulsions within the same illness than those with body temperatures above 39 degrees C (Group 2). This occurred when the body temperature rose above that which had triggered the initial febrile convulsion. Children in Group 1 were also over three times more likely to experience recurrent febrile convulsion in subsequent illnesses than those in Group 2. As for subsequent development of afebrile convulsion or epilepsy, although the risk was low, it only occurred in Group 1. It is suggested that the known association between multiple convulsions, recurrent febrile convulsions and epilepsy may be due to the single predisposing factor of a low degree of fever at the onset of febrile convulsion. Each child with febrile convulsion may have his own threshold for eliciting a convulsion with fever; the lower this threshold is, the more likely are subsequent convulsions.     

幼儿急疹合并热性惊厥的临床特征

目的 探讨幼儿急疹合并热性惊厥的临床特征.方法 回顾性总结本院2005年1月至2008年2月确诊的幼儿急疹病例和热性惊厥病例,对幼儿急疹并热性惊厥的31例患儿的临床资料进行总结,与其他热性惊厥患儿及幼儿急疹未合并热性惊厥者对比,并结合文献进行分析.结果 幼儿急疹合并热性惊厥患儿占所有热性惊厥的17.1%(31/181),占2岁内热性惊厥的24.4%(31/127),占幼儿急疹患儿的15.7%(31/198);幼儿急疹并热性惊厥患儿出现热性惊厥的平均年龄为(0.85 4±0.38)岁,早于一般的热性惊厥患儿(2.41±1.30)岁,P<0.01;与不伴热性惊厥的幼儿急疹患儿比较,伴热性惊厥者的性别、年龄、最高体温、热程、出疹时间均无显著差别(P>0.05),而热性惊厥家族史有显著差别(P<0.05).结论 遗传因素是导致幼儿急疹并热性惊厥发作的一个危险因素;幼儿急疹并热性惊厥时一般预后良好,但要警惕发生严重中枢神经系统损伤的可能性,如癫痫.对于1岁内初次发热并出现热性惊厥的患儿要注意幼儿急疹的可能.     

Zinc in CSF of patients with febrile convulsion

OBJECTIVE: This prospective study was carried out from July-December 1999 to see the status of zinc in CSF of children with febrile convulsion and to compare this to that of control. METHODS: Forty-two cases of febrile convulsion and 30 controls (fever without convulsion) were enrolled into the study. CSF zinc was estimated by atomic absorption spectrophotometry (AAS) in Atomic Energy Center, Dhaka and compared between the two groups. RESULTS: The mean zinc level in CSF in the study sample was 40.19mgm/L and that in control was 74.98mgm/L. This difference was statistically significant (p<0.001). CONCLUSION: The study concludes that a significantly lower of zinc exists in CSF of children with febrile. However no relationship was found between CSF zinc status with age, sex, degree & duration of fever and time of lumbar puncture after convulsion.     

Febrile convulsions and sudden infant death syndrome

It has been suggested that sudden infant death syndrome (SIDS) and febrile convulsions are related aetiologically. We compared the risk of SIDS in 9877 siblings of children who had had febrile convulsions with that of 20 177 siblings of children who had never had febrile convulsions. We found no support for the shared susceptibility hypothesis.     

Febrile convulsions and sudden infant death syndrome.

It has been suggested that sudden infant death syndrome (SIDS) and febrile convulsions are related aetiologically. We compared the risk of SIDS in 9877 siblings of children who had had febrile convulsions with that of 20 177 siblings of children who had never had febrile convulsions. We found no support for the shared susceptibility hypothesis.     

Viral infections and recurrences of febrile convulsions

To determine whether complicated febrile seizures occur more often in children with a proven viral infection, we performed viral examinations on 144 children with febrile convulsions, of whom 112 had simple and 32 had complicated seizures. A diagnosis of virus infection was verified in 46% of the former patients and 53% of the latter. Three adenoviruses, one parainfluenza virus type 2 and one type 3, one respiratory syncytial virus, one echovirus type 11, one herpes simplex virus type 2, and one influenza B virus were isolated from the cerebrospinal fluid. A simple febrile convulsion occurred in seven children with a positive cerebrospinal fluid viral isolation, and two had a complex febrile seizure. In a follow-up of 2 to 4 years (mean 3.3 years), 21 of the 107 children with simple seizures (19.6%) and 3 of the 32 children with complicated seizures (9.4%) had recurrent febrile seizures. The children with positive evidence for a viral infection, even with a virus isolated from the cerebrospinal fluid, had no more recurrences than those without any proven viral infection. We conclude that children with a proven viral infection have no worse prognosis than those without.     

Low sodium levels in serum are associated with subsequent febrile seizures

Fever plays an important role in causing disturbances in fluid and electrolyte balance. Hyponatraemia has been thought to enhance the susceptibility to seizures associated with febrile illnesses in childhood. We have studied serum electrolyte levels in children with simple and complicated febrile convulsions. Sodium levels were lower in those children with complicated convulsions in comparison with those having simple convulsions (136.07 ± 3.06 mmoll⁻¹, mean ± SD, n = 42, and 137.62 ±2.63mmoir¹, n = 71, respectively; p < 0.01, Student's Mest). The sodium concentrations were lowest in children with repeated seizures (134.20 ± 2.30 mmoll⁻¹, n= 15) compared with children having simple ( p < 0.01, ANOVA, Duncan's test) or other complicated types of febrile convulsions: focal seizures (137.08 ± 3.82 mmoir¹, n = 12, p < 0.01), seizures lasting longer than 15 minutes (138.00 ± 2.45 mmoll⁻¹, n = 5, p < 0.05) and children over 5 years (136.70 ±2.06 mmoll⁻¹, n = 10, p < 0.05). Serum potassium levels showed no statistically significant differences between the patient groups. Our results show that hyponatraemia may increase the risk for multiple convulsions during the same febrile illness.     

Hydroxykynurenine/hydroxyanthranilic acid ratios and febrile convulsions

Hydroxykynurenine/hydroxyanthranilic acid ratios were measured in children with febrile convulsions, afebrile fits, and fever, as well as in healthy controls. Increased ratios were found not only in the children who had fits but also in the children who were febrile and did not have fits. It is suggested that a raised hydroxykynurenine/hydroxyanthranilic acid ratio does not necessarily indicate vitamin B6 deficiency but may represent a nonspecific response of tryptophan metabolism to stress.     

Proinflammatory cytokines, prostaglandins and zinc in febrile convulsions

BACKGROUND: Some changes in the levels of proinflammatory cytokines, prostaglandins and zinc (Zn) in peripheral blood and cerebrospinal fluid (CSF) have been suggested to occur for the pathogenesis of febrile convulsions (FC). METHODS: In order to test this hypothesis, the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta and prostaglandins (PGE(2), PGF(2 alpha), PGD(2)) in the CSF and plasma and the levels of Zn in serum and CSF were investigated in children during the acute and late phases of FC. Results were compared with control subjects with meningismus. RESULTS: During the acute phase of FC, children had significantly elevated plasma levels of IL-1 beta, CSF levels of TNF-alpha, plasma levels of PGE(2), PGF(2 alpha) and PGD(2) and CSF levels of PGD(2) (P<0.05). A positive correlation between the degree of fever and plasma IL-1 beta levels was observed in both patients and controls. Three months after the acute phase of FC, plasma levels of IL-1 beta had returned to levels seen in controls. Children with FC also had significantly decreased serum Zn levels during the acute phase (P<0.05). However, there was no significant difference between the groups with respect to CSF Zn levels (P>0.05). CONCLUSIONS: During the acute phase of FC, patients had significantly increased plasma IL-1 beta and prostaglandin levels and decreased serum Zn levels. These changes may be responsible for FC pathogenesis.     

CSF Glucose Concentrations in Infants with Febrile Convulsions and the Possible Effect of Acetaminophen

The present study was done to explore the relationship between the cerebrospinal fluid (CSF) glucose concentration, body temperature, seizure duration, and acetaminophen administration. Retrospective record review of 117 consecutive febrile convulsive infants aging 3 to 18 months admitted to Bahrami Children Hospital were studied. There was a positive correlation between CSF glucose level and body temperature in those who had not taken acetaminophen before admission (r = 0.515, n = 83). CSF glucose levels were significantly higher (P = 0.014) in febrile children (75.33 mg/dL, n =70) as compared with afebrile children (66.16 mg/dL, n = 13). In those administered acetaminophen there was a negative correlation between the CSF glucose level and body temperature (r = - 0.389, P = 0.023, n = 34). CSF glucose concentration was not significantly different (P = 0.076) in those who had taken acetaminophen than those who had not taken. Type of febrile seizure, fever, convulsion duration and multiplicity were not significantly correlated with CSF glucose concentration.     

Febrile convulsion during the acute phase of Kawasaki disease

BACKGROUND: Although seizures occur in association with meningitis or encephalitis in Kawasaki disease, febrile convulsions in Kawasaki disease are considered to be extremely rare. The aim of the present study is to elucidate the incidence of febrile convulsion in the acute phase of Kawasaki disease, in Niigata City General Hospital, Niigata, Japan. METHODS: The study included 177 patients with Kawasaki disease. Patients ranged in age from 2 months to 10 years (mean age 26.89 +/- 22.44 months). The study included 105 males and 72 females. The clinical records of Kawasaki disease patients were examined retrospectively. RESULTS: Febrile convulsions were not recognized in these 177 patients throughout the course of the disease, despite the presence of a high grade fever and their young age. However, eight of the 177 patients had experienced simple febrile convulsions during other febrile illness except for those with Kawasaki disease. In the acute phase of Kawasaki disease, only two patients showed generalized convulsion associated with prolonged consciousness disturbance and pleocytosis in the cerebrospinal fluid. CONCLUSION: The incidence of febrile convulsions in the acute phase of Kawasaki disease might be extremely low, confirming the results of previous reports. Kawasaki disease is characterized by systemic vasculitis and is sometimes complicated by intracranial vasculitis. The incidence of electroencephalographic abnormalities and pleocytosis in the cerebrospinal fluid is higher in patients with Kawasaki disease. However, the reason why febrile convulsions did not occur in the acute phase of Kawasaki disease remains unknown, despite the presence of central nervous system involvement.