Manganese and selenium concentrations in cerebrospinal fluid of seriously ill children.

BACKGROUND: The homeostasis of essential trace elements such as selenium and manganese may be altered in patients with severe diseases of various etiologies (trauma brain injuries, tumors, leukemias, lymphomas, neurological diseases). METHODS: Concentration of manganese and selenium were determined in cerebrospinal fluid by electrothermal atomic absorption spectrometry in 50 hospitalized children with various clinical ethiologies including oncological, neurological, and brain related diseases. RESULTS: The concentrations of manganese in cerebrospinal fluid of children were 0.97±0.67 µg/L. The concentrations of selenium were 13.3±3.5 µg/L. The concentrations were similar as published in adults. The values did not correlated with the age, gender and severity of the disease. CONCLUSION: We evaluated values of selenium and manganese in cerebrospinal fluid of seriously diseased children.

Cerebral folate deficiency.

Cerebral folate deficiency (CFD) is defined as any neurological syndrome associated with a low cerebrospinal fluid (CSF) concentration of 5-methyltetrahydrofolate (5MTHF) in the presence of normal peripheral folate status. CFD has a wide clinical presentation, with reported signs and symptoms generally beginning at around 4 months of age with irritability and sleep disturbances. These can be followed by psychomotor retardation, dyskinesia, cerebellar ataxia and spastic diplegia. Other signs may include deceleration of head growth, visual disturbances and sensorineural hearing loss. Identification of CFD is achieved by determining 5MTHF concentration in CSF. Once identified, CFD can in many cases be treated by administering oral folinic acid. Supplementation with folic acid is contraindicated and, if used, may exacerbate the CSF 5MTHF deficiency. Generation of autoantibodies against the folate receptor required to transport 5MTHF into CSF and mutations in the folate receptor 1 (FOLR1) gene have been reported to be causes of CFD. However, other mechanisms are probably also involved, as CFD has been reported in Aicardi-Goutiere's and Rett syndromes and in mitochondriopathies. Several metabolic conditions and a number of widely used drugs can also lead to a decrease in the concentration of CSF 5MTHF, and these should be considered in the differential diagnosis if a low concentration of 5MTHF is found following CSF analysis.

Prevention of brain disease from severe 5,10-methylenetetrahydrofolate reductase deficiency.

Over a four-year period, we collected clinical and biochemical data from five Amish children who were homozygous for missense mutations in 5,10-methylenetetrahydrofolate reductase (MTHFR c.1129C>T). The four oldest patients had irreversible brain damage prior to diagnosis. The youngest child, diagnosed and started on betaine therapy as a newborn, is healthy at her present age of three years. We compared biochemical data among four groups: 16 control subjects, eight heterozygous parents, and five affected children (for the latter group, both before and during treatment with betaine anhydrous). Plasma amino acid concentrations were used to estimate changes in cerebral methionine uptake resulting from betaine therapy. In all affected children, treatment with betaine (534+/-222 mg/kg/day) increased plasma S-adenosylmethionine, improved markers of tissue methyltransferase activity, and resulted in a threefold increase of calculated brain methionine uptake. Betaine therapy did not normalize plasma total homocysteine, nor did it correct cerebral 5-methyltetrahydrofolate deficiency. We conclude that when the 5-methyltetrahydrofolate content of brain tissue is low, dietary betaine sufficient to increase brain methionine uptake may compensate for impaired cerebral methionine recycling. To effectively support the metabolic requirements of rapid brain growth, a large dose of betaine should be started early in life.

Cerebral folate deficiency: life-changing supplementation with folinic acid.

Cerebral folate deficiency is characterized by low cerebrospinal fluid (CSF) concentrations of 5-methyltetrahydrofolate and a broad spectrum of clinical signs and symptoms. A patient with progressive spasticity, gait disturbance, speech difficulties, initially diagnosed as a recessive spastic paraplegia recovered on folinic acid (15-30 mg/day) and her 5-methyltetrahydrofolate in CSF normalized. This report demonstrates the importance of CSF investigation in the diagnosis of cerebral folate deficiency and efficiency of folinic acid (5-formyltetrahydrofolate) supplementation.

Increased S100beta in the cerebrospinal fluid of patients with frontotemporal dementia.

Levels of S100beta, a calcium-binding protein found in astrocytes, were measured using a sandwich ELISA in the cerebrospinal fluid (CSF) of patients with frontotemporal dementia and Alzheimer's disease and compared with controls. Mean CSF S100beta concentrations were significantly raised in patients with frontotemporal dementia when compared with healthy controls (0.49 +/- 0.28 vs. 0.22 +/- 0.08 ng/ml, P < 0.001). There was no correlation between age at disease onset, disease severity or length of illness. The increased concentration of CSF S100beta seen in frontotemporal dementia may reflect the marked astrocytosis seen in this condition.

Immunoreactive LHRH in cerebrospinal fluid: the clinical significance in intracranial diseases.

Cerebrospinal fluid (CSF) and plasma levels of luteinizing hormone-releasing hormone (LHRH) were measured by RIA in 46 patients with acute intracranial diseases, ie, cerebral bleeding (group A), cerebral thrombosis (B), head injury (C) and meningitis (D), and the results were compared to those obtained in 21 patients with non-intracranial diseases (group E; control). Immunoreactive LHRH concentrations in CSF (CSF IR-LHRH) of 8 postmenopausal women in group E ranged 1.3 to 6.1 (mean +/- SE: 3.1 +/- 0.6) pg/ml, and those of 5 other women and 8 men with group E ranged 1.0 to 5.6 (3.6 +/- 0.4)pg/ml. In 7 out of 15 patients in group A(7/15), CSF IR-LHRH were above the levels seen in group E. In group B, C and D, CSF IR-LHRH were above the control levels in 9/15, 1/9, 3/7, respectively. The changes in plasma LHRH were not clear in postmenopausal patients in groups A and B. Plasma IR-LHRH in other women and men in group A were above the control levels in 2 out of 9 patients (2/9). Those in groups B, C and D were above the control levels in 3/8, 1/9, 2/7, respectively. Moreover, both plasma and CSF IR-LHRH of 13 patients in group A or B in chronic stage were within the control ranges. In cases observed following the time course, the occasionally increased IR-LHRH in plasma and CSF tended to decrease following the abatement of the diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

[Selenium concentration in the cerebrospinal fluid of children]. / Die Selenkonzentration im Liquor cerebrospinalis von Kindern.

Following a wet digestion of 0.5-2.0 ml cerebrospinal fluid in an open system using 2.0 ml nitric acid and 1.0 ml perchloric acid (240 degrees C) and a reduction step with 1.0 ml hydrochloric acid, Selenium can be determined polarographically after adding 100 micrograms Copper(II)-ions to the analyte (15 ml; water/perchloric acid). Selenium concentrations in cerebrospinal fluid of children younger than one year (2.49 +/- 1.67 ng/ml) are significantly higher (p = 0.0074) than those of older children (1.28 +/- 0.97 ng/ml). Independent of the children age and diseases the Selenium concentrations correlate distinctly with cell numbers and protein contents. A correlation between Selenium content and cell numbers alone could not be proved. The nonsignificant differences between the Selenium concentrations in cerebrospinal fluids of children with hydrocephalus, leukemia (with or without involvement of the central nervous system), and other diseases, respectively, may be interpreted by considering the protein content of the cerebrospinal fluid and the age of the children.

[Selenium concentration in the cerebrospinal fluid of children]. / Die Selenkonzentration im Liquor cerebrospinalis von Kindern.

Following a wet digestion of 0.5-2.0 ml cerebrospinal fluid in an open system using 2.0 ml nitric acid and 1.0 ml perchloric acid (240 degrees C) and a reduction step with 1.0 ml hydrochloric acid, Selenium can be determined polarographically after adding 100 micrograms Copper(II)-ions to the analyte (15 ml; water/perchloric acid). Selenium concentrations in cerebrospinal fluid of children younger than one year (2.49 +/- 1.67 ng/ml) are significantly higher (p = 0.0074) than those of older children (1.28 +/- 0.97 ng/ml). Independent of the childrens age and diseases the Selenium concentrations correlate distinctly with cell numbers and protein contents. A correlation between Selenium content and cell numbers alone could not be proved. The non-significant differences between the Selenium concentrations in cerebrospinal fluids of children with hydrocephalus, leukemia (with or without involvement of the central nervous system), and other diseases, respectively, may be interpreted by considering the protein content of the cerebrospinal fluid and the age of the children.

[Determination of pituitary hormones in cerebrospinal fluid in normal subjects and in hypothalamo-pituitary diseases. Secreting or non-secreting pituitary adenoma, empty sella syndrome, hypothalamic syndromes]. / Le dosage des stimulines hypophysaires dans le liquide céphalo-rachidien chez le sujet normal et en pathologie hypothalamo-hypophysaire. Adénome hypophysaire sécrétant ou non sécrétant, selle turcique vide, syndromes hypothalamiques.

Cerebrospinal fluid (CSF) and serum concentrations of TSH, ACTH, FSH, LH, GH and PRL were measured simultaneously in 34 subjects divided into 3 groups: I--12 normal subjects (6 males and 6 females); II--12 prolactin adenomas (3 males and 9 females); III--5 empty sella syndromes; 3 hypothalamic disorders; 1 chromophobe adenoma; 1 pituitary dwarfism. It is concluded that:--pituitary hormones are the normal constituents of CSF but the level can be undetectable and in any case lower than the serum level; --there is a positive correlation between serum and CSF concentration of PRL when serum PRL is higher than 20 ng/ml, indicating that the CSF level is influenced by serum level; --in prolactin adenomas only prolactin is elevated in the CSF; --there is no correlation between the high level of CSF-PRL and a suprasellar extension of the adenoma.

[Determination of 6 pituitary hormones in the cerebrospinal fluid. Control subjects, prolactin adenomas, empty sella syndrome and hypothalamic disorders (author's transl)]. / Dosage de 6 stimulines hypophysaires dans le liquide céphalo-rachidien. Sujets normaux, adénomes à prolactine, selles vides, syndromes hypothalamiques.

Cerebrospinal fluid (CSF) and serum concentrations of TSH, ACTH, FSH, LH, GH and PRL were measured simultaneously in 34 subjects divided into 3 groups: I-12 normal subjects (6 males and 6 females); II-12 prolactin adenomas (3 males and 9 females); III-5 empty sella syndromes, 3 hypothalamic disorders, 1 chromophobe adenoma, 1 pituitary dwarfism. It is concluded that: 1) pituitary hormones are the normal constituents of CSF but the level can be undetectable and in any case lower than the serum level. 2) there is a positive correlation between serum and CSF concentration of PRL when serum PRL is higher than 20 ng/ml, indicating that the CSF level is influenced by serum level. 3) in prolactin adenomas, only prolactin is elevated in the CSF. 4) there is no correlation between the high level of CSF-PRL and a suprasellar extension of the adenoma.

Somatostatin in human cerebrospinal fluid.

To determine whether somatostatin is found in the hypothalamus and extrahypothalamic brain, we studied autopsy brain tissue by specific immunoassay. The hypothalamus contained the highest concentration (16.7 +/- 2.4 S.D. pg per microgram of protein), with small amounts in brainstem, cerebral cortex, cerebellum, pineal gland and spinal cord. Cerebrospinal fluid of seven neurologically normal persons also contained somatostatin in concentrations ranging from 15 to 55 pg per milliliter. To determine whether brain disease leads to abnormal cerebrospinal-fluid somatostatin, we examined 30 patients with neurologic disease, of whom 20 of 24 with cord or cerebral disease had concentrations above the highest normal level. The wide variety of diseases with somatostatin elevation suggests nonspecific leakage from damaged brain tissue. Cerebrospinal-fluid somatostatin may provide a good index of brain damage. Although correlated statistically with cerebrospinal-fluid protein, somatostatin concentration in five of 24 cases exceeded the upper limit of normal by 3 S.D. while protein was normal.

Thiamine triphosphate deficiency in subacute necrotizing encephalomyelopathy.

Extracts of tissue fluids from a patient with subacute necrotizing encephalomyelopathy inhibit thiamine pyrophosphate-adenosine triphosphate phosphotransferase of rat brain. Brain tissue from the patient, in contrast to normal brain tissue, contained essentially no thiamine triphosphate, although thiamine and its other phosphate esters were present in normal concentrations. These findings suggest a relation between this disease and thiamine triphosphate.