Osteopontin is highly secreted in the cerebrospinal fluid of patient with posterior pituitary involvement in Langerhans cell histiocytosis.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease caused by clonal proliferation of CD1a+ CD207+ cells. Distinguishing pituitary involvement was essential in stratification and treatment of patients with LCH. The diagnosis of pituitary involvement is mainly dependent on hormone abnormalities in the anterior pituitary and magnetic resonance imaging (MRI) scanning in posterior pituitary. Diabetes insipidus (DI) is a serious sequelae and often occurred with pituitary involvement. It is reported that osteopontin (OPN) is highly secreted in the cerebrospinal fluid (CSF) of patients with neurodegenerative diseases in LCH (LCH-ND). However, patients with posterior pituitary involvement account for a larger portion in our hospital. Whether the OPN level could be an auxiliary diagnostic marker for the posterior pituitary involvement or not is still unknown. METHODS: In our study, we collected CSF samples of 57 children with LCH. The secreted OPN (sOPN) levels in CSF were measured through enzyme-linked immunosorbent assay (ELISA). RESULTS: After the retrospective analysis of 57 patients with LCH, we found that the sOPN levels in CSF of children with posterior pituitary involvement were significantly higher than that of other groups. After the Pearson Chi-Square test, Fisher's exact test and ROC analysis, we found that the sOPN levels were significantly correlated with posterior pituitary involvement. The cut-off value is 214.14 ng/mL. CONCLUSION: The sOPN levels were elevated in CSF of LCH children with posterior pituitary involvement. Analysis of the sOPN level may provide more accurate auxiliary diagnostic techniques for the clinic.

Solitary Langerhans cell histiocytosis located in the neurohypophysis with a positive titer HCG-ß in the cerebrospinal fluid.

INTRODUCTION: Beta-human chorionic gonadotropin (HCG-ß) is considered to be a useful tumor marker for germ cell tumors (GCTs); however, various tumors other than GCTs, including cystic pituitary adenomas, Rathke's cleft cysts, and craniopharyngiomas, were reported to express HCG-ß. CASE REPORT: We herein present the case of a 5-year-old boy who presented with polyuria and had a solitary lesion in the neurohypophysis with a positive HCG-ß titer in the cerebrospinal fluid. Under a preoperative diagnosis of germinoma, a biopsy was performed from the posterior pituitary lobe via the transsphenoidal endoscopic approach and the histological diagnosis was revealed to be Langerhans cell histiocytosis (LCH). CONCLUSIONS: The finding of a slightly positive HCG-ß titer in the cerebrospinal fluid (CSF) cannot exclude the possibility of LCH, and we strongly recommend a histological diagnosis for the diagnosis of a solitary neurohypophysial lesion.

The challenge of profound hypoglycorrhachia: two cases of sarcoidosis and review of the literature.

We report two cases of sarcoidosis which were initially misdiagnosed due to profound hypoglycorrhachia. Sarcoidosis is a systemic inflammatory disorder which can mimick other entities and has a vast array of presentations including altered mentation and signs of increased intracranial pressure. Though hypoglycorrhachia has been described previously, these two cases are unique in not only the level of hypoglycorrhachia but also the diagnostic challenge presented. We propose that sarcoidosis should be in the differential of all cases of CNS diseases with any level of hypoglycorrhachia.

Central system nervous tuberculosis in infants.

The lack of specific symptoms and signs in patients with tuberculous meningitis makes early diagnosis difficult. In this report, we reviewed the clinical features and laboratory findings of 6 infants with central system nervous tuberculosis during a 10-year period. One of the patients had multifocal tuberculosis. The mean time to the diagnosis was 32 +/- 13.4 days. A contact source was identified in only 2 patients. All 6 patients had abnormal cerebrospinal fluid findings, less than 500 cells/microL with lymphocytic predominance. Computerized tomography (CT) and/or magnetic resonance imaging (MRI) revealed hydrocephalus with basal enhancement in 2 patients. One patient developed pontocerebellar and pituitary tuberculomas, which were responsible for compression and diabetes insipidus, 1 year after antituberculous treatment. These localizations are very rare. On the follow-up, 3 patients had hypoacousia and only 1 had severe sequelae, despite a diagnostic delay.

Biomarkers in the cerebrospinal fluid and neurodegeneration in Langerhans cell histiocytosis.

BACKGROUND: Progressive neurodegeneration may result in potentially severe cognitive and motor dysfunctions as a complication of Langerhans cell histiocytosis (LCH), a suggested IL-17A-associated inflammatory condition. To detect this complication (CNS-LCH) early and to evaluate the potential efficacy of therapeutic interventions, biomarkers detecting and measuring ongoing neurodegeneration would be valuable. We evaluated cerebrospinal fluid (CSF) biomarkers of ongoing neurodegeneration in CNS-LCH patients. PROCEDURE: Nine patients with endocrine, neuromotor, cognitive or/and behavioral abnormalities as well as neuroradiological evidence of CNS-LCH were evaluated 4-12 years after LCH diagnosis for CSF levels of neurofilament protein light chain (NF-L), glial fibrillary acid protein (GFAp), and total tau protein (TAU). Two patients were analyzed longitudinally. One hundred ten children with newly diagnosed acute lymphoblastic leukemia (ALL) served as controls. RESULTS: NF-L, TAU, and GFAp levels were elevated in four, six, and eight of nine patients studied, respectively. NF-L (P < 0.001) and GFAp (P < 0.001) were higher in patients than in controls (TAU not analyzed in controls). The patient with most severe clinical and neuroradiological CNS-LCH displayed the highest levels of NF-L and GFAp whereas three patients without signs of systemic disease had low TAU levels and normal/slightly elevated NF-L. NF-L tended to be higher at radiological progression of neurodegeneration than at status quo (P = 0.07). Notably, we experienced frequent lumbar puncture complications in these patients. CONCLUSIONS: CSF levels of NF-L, TAU, and GFAp appear to be elevated in CNS-LCH. It would be valuable if these markers were validated in order to serve as markers for early CNS-LCH, to monitor disease progression and to evaluate various treatment attempts for CNS-LCH.

Hypophysitis secondary to ruptured Rathke's cyst mimicking neurosarcoidosis.

Hypophysitis secondary to a ruptured Rathke's cyst is rare. We describe a 53-year-old female who presented with headache and subsequently developed aseptic meningitis and panhypopituitarism. MRI findings and concomitant cardiac arrhythmia and peripheral vasculitis led to a provisional diagnosis of neurosarcoidosis. There were no respiratory manifestations of sarcoidosis. Improvement was noted with empirical treatment with steroids. Pituitary biopsy was undertaken to confirm the diagnosis prior to treatment with long-term immunosuppression for putative neurosarcoidosis. The biopsy revealed lymphocytic hypophysitis secondary to a ruptured Rathke's cyst. This report highlights a rare pathology and the importance of a tissue diagnosis before undertaking non-surgical management of a pituitary mass.

Somatomedin levels in cerebrospinal fluid from adults with pituitary disorders.

Somatomedin levels in cerebrospinal fluid (CSF) were determined in patients with acromegaly, pituitary deficiency, prolactinoma, and Cushing's disease by radioimmunoassay (RIA) for insulin-like growth factor 1 (IGF-1) and for IGF-2 as well as a radioreceptor assay (RRA) with adult human brain plasma membranes and IGF-2 as ligand. The mean value of RIA-IGF-2 (31 +/- 1.6 ng/ml) predominated over that of RIA-IGF-1 (5.8 +/- 0.3 ng/ml), but 10 times higher levels were found by RRA-IGF-2. Patients with acromegaly were not found to have higher values than those with GH deficiency even after corrections were made for possible leakage across the blood-CSF barrier. No correlations were found between CSF somatomedin levels determined by different techniques and immunoreactive IGF-1 or GH in the peripheral circulation except for a positive correlation between CSF RIA-IGF-2 and serum IGF-1 in patients with acromegaly. These findings suggest that somatomedins in CSF consist primarily of IGF-2-like peptides which are derived from production within the central nervous system or pituitary gland rather than from transport across the blood-CSF barrier.

Immunoreactive corticotropin-releasing factor concentrations in cerebrospinal fluid from patients with hypothalamic-pituitary-adrenal disorders.

The concentrations of immunoreactive corticotropin-releasing factor (I-CRF) in human cerebrospinal fluid (CSF) were measured utilizing immunoaffinity chromatography and RIA in patients with no endocrine disease, patients with Cushing's disease, Nelson's syndrome, Sheehan's syndrome, Addison's disease and steroid treated patients. On high performance liquid chromatography, the elution profile and retention time of I-CRF in CSF were not identical with ovine CRF. I-CRF concentrations in CSF from patients with Cushing's disease and Sheehan's syndrome were lower than those from normal subjects, however those from patients with Nelson's syndrome and Addison's disease were within the normal range. I-CRF concentrations in CSF from patients with Cushing's disease returned to normal levels 2-9 months after pituitary adenomectomy. These results suggest that CSF I-CRF concentrations are reduced by increased plasma corticosteroid levels.

[Ischemic pituitary apoplexy and cerebrovascular accident]. / Apoplexie hypophysaire ischémique et accident vasculaire cérébral.

Operative findings of degenerative changes in pituitary adenomas are not uncommon; however, clinical apoplexy is rare. We report the case of a 43-year-old man who presents a sudden right hemiplegia with aphasia and right ophthalmoplegia, in relation with an ischemic pituitary apoplexy and cerebral vasospasm. A few cases of arterial obstruction or vasospasm associated with pituitary apoplexy have been reported in the literature. Cerebral arterial spasm has also been observed after pituitary surgery. Inclusion of blood or necrotic material in the subarachnoid space seems not to be the only mechanism of vasospasm. The role of hypothalamic dysfunction is considered.

Polyamine levels in CSF from patients with pituitary tumors or nonneoplastic pituitary disease.

Cerebrospinal fluid polyamine determinations were performed in 21 patients harboring pituitary tumors and six patients with nonneoplastic pituitary disease. Although CSF putrescine levels were significantly elevated in some patients harboring tumors, other patients showed no elevation. Polyamine levels did not correlate with tumor size, as assessed by the presence or absence of suprasellar extension. Data on patients harboring nonneoplastic pituitary disease were variable. Compared with other findings from this laboratory on the use of polyamine levels for the diagnosis and management of other brain tumors, these findings suggest that CSF polyamine levels will not have a significant diagnostic role in the treatment of patients suspected to have pituitary disease.

The primary empty sella syndrome: analysis of the clinical characteristics, radiographic features, pituitary function and cerebrospinal fluid adenohypophysial hormone concentrations.

Twelve cases of the primary empty sella syndrome were analyzed in regard to clinical findings, roentgenographic features, pituitary function and cerebrospinal fluid adenohypophysial hormone concentration. The findings were compared with those in 247 cases of the primary empty sella syndrome reviewed from the literature in order to determine the major characteristics of this disorder. The majority of patients are obese, multiparous women with normal pituitary reserve, normal visual fields and undetectable adenohypophysiol hormone concentrations in cerebrospinal fluid. In addition occasional patients witll have hypertension, pseudotumor cerebri and cerebrospinal fluid rhinorrhea. Patients who present with the typical features of the primary empty sella syndrome should be evaluated periodically with pituitary function testing, visual field examinations and cerebrospinal fluid adenohypophysial hormone determinations. If these parameters remain normal during careful follow-up studies, the patient is likely to have an empty sella, and pneumoencephalographic and angiographic studies can be avoided.

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.

Cerebrospinal fluid prolactin: a reflection of abnormal prolactin secretion in patients with pituitary tumors.

Cerebrospinal fluid prolactin levels were determined in 33 patients with pituitary disease, 3 pregnant women at term and 30 control subjects. Prolactin which was immunologically similar to the human prolactin standard was detected by radioimmunoassay in the CSF of most of these subjects. Elevated serum and CSF PRL concentrations were found in three pregnant subjects and in twelve patients with putuitary tumors. Ten patients with pituitary tumors had serum PRL concentrations greater than their corresponding CSF PRL levels. A significant correlation was noted between the elevated serum and CSF prolactin levels in the twelve hyperprolactinemic patients which suggested that the CSF prolactin concentration was influenced by the serum PRL level. Two patients with pituitary tumor however, had CSF prolactin concentrations higher than their serum levels, which suggested that direct secretion of prolactin from the tumor to the CSF can also occur. Three patients with chromophobe adenomas had normal serum PRL concentrations and elevated CSF prolactin levels which differentiated them from fifteen patients with the primary empty sella syndrome who had normal serum and CSF prolactin levels. The finding of normal CSF prolactin levels in the primary empty sella patients argues against the postulate that the diaphragma sellae significantly influences CSF pituitary peptide concentrations.

Cerebrospinal fluid hormone concentration in the evaluation of pituitary tumors.

Cerebrospinal fluid (CSF) concentrations of corticotropin, growth hormone, thyrotropin, prolactin, luteinizing hormone, and follicle stimulating hormone were measured in 28 patients with various neurologic disorders, in 49 patients with pituitary tumors of whom 22 had suprasellar extension, and in 6 patients with craniopharyngiomas. With the exception of 1 patient with pseudotumor cerebri, CSF adenohypophyseal hormone concentrations were low in patients with neurologic disease and in patients with pituitary tumor without suprasellar extension. In marked contrast, 21 to 22 patients with suprasellar extension of a pituitary tumor and 2 of 6 patients with a craniopharyngioma had elevations of one or more CSF adenohypophyseal hormones. Posttreatment CSF adenohypophyseal hormone levels fell from previously elevated levels in 4 of 5 patients. These data suggest that an elevated CSF adenohypophyseal hormone concentration is a sensitive indicator of suprasellar extension of a pituitary tumor, and posttreatment measurements are useful in determining efficacy of therapy.