Phenytoin impairs the bioavailability of dexamethasone in neurological and neurosurgical patients.

Plasma concentration-time data after oral and intravenous administration of dexamethasone have been subjected to pharmacokinetic analysis in six neurological or neurosurgical patients taking the steroid with phenytoin, and in nine patients (one studied twice) taking dexamethasone without phenytoin. An additional patient was studied before and during phenytoin intake. Apparent volume of distribution was similar in the two groups, but the group treated with phenytoin had an almost statistically significantly shorter dexamethasone mean terminal half-life, an approximately trebled mean plasma clearance, and a mean oral bioavailability of the steroid of only 33%, compared with a mean 84% oral bioavailability in those not receiving phenytoin. To achieve a given plasma dexamethasone concentration, patients treated with the steroid and phenytoin may need oral dexamethasone doses several times those required by patients not receiving phenytoin.     

Amyloid in neurosurgical and neurological practice.

The amyloidoses are a diverse group of diseases characterized by the deposition of specific proteins with distinct affinity to the dye Congo red, collectively called amyloid. The amyloidogenic proteins have acquired an abnormal, highly ordered, beta-pleated sheet configuration with a propensity to self-aggregate. The amyloid may be distributed in different organs with a remarkable diversity. Two broad categories of amyloidoses are recognised: The systemic (consisting of the primary or light chain form, the secondary or reactive form and the familial or hereditary form) and the localised that target specific organs. A tropism of amyloid proteins to the neural tissue produces certain patterns of central nervous system diseases: cerebral amyloid angiopathy, a substrate of spontaneous intracerebral haemorrhage; mature neuritic plaques found in Alzheimer disease and a subset of prion diseases; a topographically restricted accumulation of extracellular proteins giving rise to tumour-mimicking masses, the amyloidomas; and finally, spinal extradural amyloid collections that occasionally are found in the context of rheumatoid arthritis. In this review article we present original illustrative cases of amyloid diseases of the central nervous system that may be encountered in neurosurgical and neurological practice. Molecular aspects and clinical management problems are discussed.     

Cortisol suppression after dexamethasone administration in patients with dementia

Sixty-four nondepressed, carefully selected senile demented inpatients underwent two 1.0 mg overnight dexamethasone suppression tests (DSTs) separated by 7 days. These patients had been in a clinically stable and drug-free state for at least six months prior to testing. The Modified Ischemic Scale score and ICD-9 criteria for Alzheimer's disease were used to dichotomize subjects into Alzheimer's and multi-infarct types of dementia. Patients with vascular dementias were significantly more likely to evidence DST nonsuppression, furthermore, DSTs in this group were less reproducible from week to week than DSTs in Alzheimer's patients.     

Pituitary adrenocortical response to high dose administration of betamethasone in neurosurgical patients (author's transl)

Using RIA technique, response patterns of ACTH-adrenocortical system to short term large dose corticosteroid therapy for neurosurgical patients were investigated. The subjects were consisted of 20 males and 13 females, ageing ranging from 10 to 60 years old. The subjects were divided into three groups according to mode of steroid administration. In the first group, 12 mg/day of betamethasone were administered for 5 days and cancelled without gradual reduction. In the second group, 12 mg/day of betamethasone were administered for 4 days and 6 mg/day of betamethasone were given for following 2 days. In the third group, 12 mg/day of betamethasone were administered for 3 days and gradual reduction of betamethasone was given for following 4-5 days. Response of plasma cortisol level to synthetic 18-ACTH were measured in all patients for 3 days after betamethasone administration cancelled. The results led to the following conclusion. 1) The second and third groups had not any clinical symptom after steroid cancelled, but one half cases of the first group had mild headache, nausea for 2 days after cancelled. 2) Recovery process of adrenocortical function in the second group is most rapidly, compared with that in other two groups. 3) In the postoperative steroid therapy in neurosurgery, it could be concluded that 4 days massive administration of steroid followed by stepwise reduction in 2 days would be functionally well tolerated by adrenocortical system.     

High dose pulsatile dexamethasone therapy in children with opsoclonus-myoclonus syndrome

Opsoclonus-myoclonus syndrome (OMS) is a rare movement disorder characterized by chaotic eye movements, myoclonus, and ataxia associated with severe irritability. Different treatment modalities including steroids and cyclophosphamide have been tried in the past often with significant side effects and variable success. Here we present 11 children, diagnosed with OMS between 1999 and 2005 and treated with high dose dexamethasone pulses. Main symptoms at presentation were opsoclonus (11/11), ataxia and/or myoclonus (11/11), irritability (10/11) associated with a neuroblastoma in four children. Number of dexamethasone pulses ranged from 6 to 60 pulses. No major side effects were reported. In 6/11 children a complete and sustained remission of OMS symptoms was achieved after 6 to 29 pulses of dexamethasone. Two children from this group have a normal development and no neurological sequelae. Two further children have minor delays in fine- and gross-motor skills. Two children despite a complete recovery of OMS symptoms have persisting developmental problems. 5/11 children still require regular dexamethasone pulses in addition to daily prednisolone (n = 1) or have received cyclophosphamide pulses meanwhile (n = 2). All children continue to have developmental and neurological difficulties. In summary treatment with high dose pulsatile dexamethasone appears to be safe and beneficial in a subgroup of patients with OMS.     

Cortisol response during different anxiogenic challenges in panic disorder patients.

The present study assessed the relation of cortisol response to anxiogenic reactivity during intravenous lactate infusion and oral fenfluramine in 12 panic disorder (PD) patients who responded positively to both challenges and in eight non-reactive control subjects. There was no significant cortisol response difference between the PD patients and the controls during lactate infusion, but there was s significant difference at 120 min during the fenfluramine challenge. These findings are consistent with the possibility that these challenges stimulate different neurobiologic mechanisms and that fenfluramine-precipitated anxiety is more akin to anticipatory or generalized anxiety than to true panic anxiety.     

Cortisol response to dexamethasone and noradrenergic function in depression

Positive correlations between measures of hypothalamic-pituitary-adrenal (HPA)-axis activity and noradrenergic turnover have been reported in depression. To investigate this relationship the authors measured peak postdexamethasone cortisol levels (8 a.m., 4 p.m. and 11 p.m.) and the 24-hour urinary 3-methoxy-4-hydroxy-phenylglycol (MHPG) flow in 84 depressed patients. The results show that there is no positive association between those measures of HPA-axis and noradrenergic activity. On the contrary, patients with severe non-suppression (greater than or equal to 10 micrograms/dl or 277 nmol/l) tended to have a lower MHPG-excretion.     

Pulsed high dose dexamethasone treatment in chronic inflammatory demyelinating polyneuropathy: a pilot study.

Six cycles of dexamethasone (40 mg per day for four sequential days) every 28 days induced remissions in 10 patients with idiopathic thrombocytopenic purpura (ITP). Whether the same results could be achieved in 10 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) was investigated by comparing the Rivermead mobility index (RMI) before and after six cycles of treatment. Three patients discontinued treatment: one because of severe nausea and vomiting and two because of neurological deterioration. All seven patients who completed treatment improved on the RMI. One of these patients had a relapse within two months after the last cycle and six patients were in remission six months after the last dexamethasone cycle. Pulsed high dose dexamethasone induced remissions ranged from at least 15 to 23 months. This treatment needs to be tested against standard treatment in a randomised study.     

Cortisol, 11-deoxycortisol, and ACTH concentrations after dexamethasone in depressed patients and healthy volunteers

The 1 mg dexamethasone suppression test was used to assess pituitary-adrenal activity in 23 depressed patients and 8 healthy volunteers. At 1600h, after administration of the test dose of dexamethasone at 2300h, levels of cortisol, 11-deoxycortisol, and corticotropin were determined following a chromatographic extraction step applying highly specific radioimmunoassay techniques. Cortisol nonsuppressors had significantly increased adrenocorticotropic hormone (ACTH) values and cortisol/11-deoxycortisol ratios. The cortisol/11-deoxycortisol ratio was regarded as a measure of biologically active ACTH. The present results, which indicate a concordance of corticotropin and corticosteroid response, suggest that the parent abnormality of dexamethasone-resistant cortisol concentrations is elevation of biologically active corticotropin.     

Intravenous immunoglobulin therapy in neurological diseases during pregnancy

Journal of Neurology - Immunological changes during pregnancy influence the course of neurological autoimmune diseases in different ways. In case of pregnancy immunmodulatory standard therapies...     

Cortisol response to dexamethasone in women with premenstrual syndrome

There were no significant differences in post-dexamethasone cortisol between the follicular and luteal phase of the menstrual cycle in both women with premenstrual syndrome (PMS) and control subjects tested on these two occasions. Within each menstrual cycle phase, there were also no differences in post-dexamethasone cortisol between the two groups. In a second group of control subjects tested on a single occasion, post-dexamethasone cortisol values were higher when subjects were tested in the middle 2 weeks of the menstrual cycle compared with the first and last weeks of the cycle. This phenomenon, possibly due to estrogen effects, suggests that post-dexamethasone cortisol should be assessed weekly in women with PMS to determine whether they also manifest this normally observed menstrual cycle phase-related pattern, or whether it is absent, reflecting a reproductive endocrine abnormality in this patient group.     

Aseptic meningitis associated with high dose intravenous immunoglobulin therapy.

Two cases of aseptic meningitis occurred in temporal association with high dose intravenous immunoglobulin therapy to treat thrombocytopenia. In neither case was any other aetiological agent identified and both patients completely recovered within a few days. This phenomenon has been reported in only one previous paediatric case.     

Cortisol, ACTH, and dexamethasone concentrations in a psychogeriatric population

Cortisol and adrenocorticotrophic hormone (ACTH) were measured at 2 time points before the administration of 1 mg of dexamethasone (day 1) and 1 time point on the following day (day 2). Thirteen severely depressed elderly patients, 15 patients with Alzheimer-type dementia (ATD), and 16 normal controls were studied. Cortisol was markedly elevated in depressed patients compared with the other subjects in day 1 samples. Following dexamethasone, both the depressed and ATD patients showed a similar elevation of cortisol compared with controls. ACTH concentrations were not significantly different between the groups before dexamethasone, but were significantly higher in both depressed and ATD patients after dexamethasone. More depressed patients than ATD patients exhibited hypersecretion of ACTH after dexamethasone. This implies that ACTH is less responsive to glucocorticoid feedback in elderly depressed patients, which may be a factor in causing hypercortisolemia.