Long term follow up in 183 high grade meningioma: A single institutional experience.

INTRODUCTION: Meningiomas are usually considered benign lesions, however a proportion of them shows a more aggressive behavior, defined high-grade meningiomas (HGM). Effective medical treatments are lacking, especially at the time of recurrence. METHODS: Through a retrospective analysis, we examined epidemiological, diagnostic, therapeutic, recurrence information and survival data of HGM treated at our institution between 2010 and 2018. RESULTS: 183 patients (105 females and 78 males), with median age of 58 years (25-88), were included; 168 were atypical, 12 anaplastic, 3 rhabdoid. Overall, m-PFS was 4.2 years, and m-OS was 10.3 years. Gross-total resection had a 5-year survival rate of 95% compared with subtotal/partial resection (86% and 67%) (p = 0.002). Higher expression of Ki-67/MIB-1 seems associated with higher risk of death (HR:1.06 with 95% CI, 1.00-1.12, p = 0.03). No statistically significant differences were seen in survival between the group managed with a wait-and-see strategy vs the group treated with RT while a difference on PFS was seen (4.1 years vs 5.2 years p = 0.03). After second recurrence, the most employed treatments were systemic therapies with a very limited effect on disease control. CONCLUSIONS: Data confirmed the aggressive behavior of HGM. The extent of resection seems to correlate with a favorable outcome regardless histological subtypes. The role of RT remains controversial, with no statistically significant impact on OS but a possible role on PFS. Recurrent HGM remains the real challenge, to date no chemotherapies are able to achieve disease control. Future research should focus on biological/molecular predictors in order to achieve a patient-tailored treatment.

Advanced MRI may complement histological diagnosis of lower grade gliomas and help in predicting survival.

MRI grading of grade II and III gliomas may have an important impact on treatment decisions. Occasionally,both conventional MRI (cMRI) and histology fail to clearly establish the tumour grade. Three cMRI features(no necrosis; no relevant oedema; absent or faint contrast enhancement) previously validated in 196 patients with supratentorial gliomas directed our selection of 68 suspected low-grade gliomas (LGG) that were also investigated by advanced MRI (aMRI), including perfusion weighted imaging (PWI), diffusion weighted imaging(DWI) and spectroscopy. All the gliomas had histopathological diagnoses. Sensitivity and specificity of cMRI preoperative diagnosis were 78.5 and 38.5 %, respectively, and 85.7 and 53.8 % when a MRI was included, respectively. ROC analysis showed that cut-off values of 1.29 for maximum rCBV, 1.69 for minimum rADC, 2.1 for rCho/Cr ratio could differentiate between LGG and HGG with a sensitivity of 61.5, 53.8, and 53.8 % and a specificity of 54.7, 43 and 64.3 %, respectively. A significantly longer OS was observed in patients with a maximum rCBV<1.46 and minimum rADC>1.69 (80 vs 55 months, p = 0.01; 80 vs 51 months, p = 0.002, respectively). This result was also confirmed when cases were stratified according to pathology (LGG vs HGG). The ability of a MRI to differentiate between LGG and HGG and to predict survival improved as the number of a MRI techniques considered increased. In a selected population of suspected LGG,classification by cMRI underestimated the actual fraction of HGG. aMRI slightly increased the diagnostic accuracy compared to histopathology. However, DWI and PWI were prognostic markers independent of histological grade.

Short-course radiotherapy in elderly patients with glioblastoma: feasibility and efficacy of results from a single centre.

BACKGROUND: The incidence of glioblastoma (GBM) in the elderly population is currently increasing, with a peak seen between 65 and 84 years. The optimal treatment in terms of both efficacy and quality of life still remains a relevant and debated issue today. The purpose of our study was to evaluate the feasibility of short-course hypofractionated accelerated radiotherapy (HART) in GBM patients aged over 70 years and with a good Karnofsky performance score (KPS). METHODS: A review of medical records at the "Istituto Neurologico C. Besta" was undertaken; patients aged ≥ 70 years who had undergone adjuvant HART for GBM between January 2000 and January 2004 were included in the study. HART was administered to a total dose of 45 Gy, 2.5 Gy/fraction, in three daily fractions for three consecutive days/cycle fractions each, delivered in two cycles (split 15 days). RESULTS: A total of 33 patients were evaluable for the current analysis. Median follow-up was 10 months. According to CTCAE (version 3.0) criteria, none of the patients developed radiation-induced neurological status deterioration or necrosis. KPS evaluation after HART was found to be stable in 73 % of patients, improved in 24 %, and worse in 3 %. The median overall survival time of the entire study population was 8 months (range 2-24). CONCLUSIONS: Our findings suggest that a hypofractionated accelerated schedule can be a safe and effective option in the treatment of GBM in the elderly.

Allergy and multiple sclerosis: a population-based case-control study.

BACKGROUND: Epidemiological studies on the association between allergic disorders, T-helper type 2 (Th2) mediated, and multiple sclerosis (MS), a T-helper type 1 (Th1)/Th17-mediated disease, provided conflicting results. OBJECTIVE: The aim of this study was to further examine the association between allergic disorders and MS. METHODS: The association between MS and previous medical history of any type of allergy has been investigated in a population-based case-control study conducted in Northern Italy, based on telephone interviews to 423 cases and 643 population controls (refusal rates 3.7% and 9.4%, respectively). Controls were a random sample of the general population. RESULTS: A history of atopic allergies seems to confer protection against MS (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.38-0.89; P = 0.012). In particular, the prevalence of allergic asthma was 4.9% in people with MS and 12% in control subjects (OR = 0.38; 95% CI 0.22-0.66, P < 0.01). No association was found between MS and nonatopic allergies. CONCLUSIONS: Our findings are confirmatory of the putative protective effect of Th2-mediated disorders on Th1 immune responses associated with MS. A unifying theory on the mechanisms by which previous history of atopic allergies may modify the risk of MS is still lacking.

Dietary interventions for multiple sclerosis.

BACKGROUND: Clinical and experimental data suggest that certain dietary regimens, particularly those including polyunsaturated fatty acids (PUFAs) and vitamins might improve outcomes in people with multiple sclerosis (MS). Diets and dietary supplements are much used by people with MS in the belief that they might improve disease outcomes. OBJECTIVES: We performed a Cochrane review of all randomised trials of dietary regimens for MS with the aim of answering MS consumers' questions regarding the efficacy and safety of these interventions. SEARCH STRATEGY: We searched the Cochrane MS Group trial register (February 2006), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Library, Issue 1, 2006, MEDLINE (PubMed) (1966 to March 2006), EMBASE (1974 to March 2006) and the bibliographies of papers found. SELECTION CRITERIA: All randomised controlled trials comparing a specific dietary intervention, diet plan or dietary supplementation, with no dietary modification or placebo, were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected articles, assessed trial quality and extracted data. Trial quality was poor, particularly as regards descriptions of randomisation, blinding and adverse event reporting. Some studies had large numbers of drop-outs; dropouts were never included in the analyses. MAIN RESULTS: PUFAs did not have a significant effect on disease progression, measured as worsening of Disability Status Scale. Omega-6 fatty acids (11-23 g/day linoleic acid) had no benefit in 75 relapsing remitting (RR) MS patients (progression at two years: relative risk (RR)=0.78, 95% CI [0.45 to 1.36]) or in 69 chronic progressive (CP) MS patients (RR=1.67, 95% CI [0.75 to 3.72]. Linoleic acid (2.9-3.4 g/day) had no benefit in CPMS (progression at two years: RR=0.78, 95% CI [0.43 to 1.42]). Slight decreases in relapse rate and relapse severity were associated with omega-6 fatty acids in some small studies, however these findings are limited by the limited validity of the endpoints.Omega-3 fatty acids had no benefit on progression at 12 months in 14 RRMS patients or at 24 months in 292 RRMS patients (RR=0.15, 95% CI [0.01 to 3.11], p= 0.22 at 12 months, and 0.82 95% CI [0.65 to 1.03], p=0.08, at 24 months). The low frequency of reported adverse events suggests no major toxicity associated with PUFA administration. No studies on vitamin supplementation and allergen-free diets were analysed as none met the eligibility criteria. AUTHORS' CONCLUSIONS: PUFAs seem to have no major effect on the main clinical outcome in MS (disease progression), and does not substantially affect the risk of clinical relapses over 2 years. However, the data available are insufficient to assess any potential benefit or harm from PUFA supplementation. Evidence bearing on the possible benefits and risks of vitamin supplementation and antioxidant supplements in MS is lacking. More research is required to assess the effectiveness of diets interventions in MS.

Active and passive smoking during pregnancy and risk of central nervous system tumours in children.

The effects of maternal active and passive smoking during pregnancy on childhood central nervous system (CNS) tumours were assessed in a population-based case-control study. The mothers of 244 children aged 0-15 years with CNS tumours and 502 control mothers were interviewed about their smoking habits. All families were resident in the region of Lombardy, Italy. Risk estimates were calculated by unconditional logistic regression, adjusted for age, sex and area of residence. Active smoking by the parents before pregnancy was not associated with increased risk of CNS tumours in the children. Active smoking by the mother during early pregnancy (approximately the first 5 weeks) was associated with a slightly increased risk of the child developing a CNS tumour (odds ratio [OR] 1.5 [95% CI 1.0, 2.3]). An increased risk of CNS tumours was found in the children of non-smoking mothers exposed regularly to tobacco smoke both in early pregnancy (OR 1.8 [95% CI 1.2, 2.6]) and in late pregnancy (OR 1.7 [95% CI 1.2, 2.5]). Although this study was retrospective, the results confirm our previous findings and suggest an association between the risk of developing CNS tumours in children and regular passive smoking by the mother during pregnancy.

Validation of Italian multiple sclerosis quality of life 54 questionnaire.

OBJECTIVES: Health related quality of life (HRQOL) inventories are multi-dimensional measures of patient-centred health status developed for clinical research. The MS quality of life 54 (MSQOL-54) is an MS-specific HRQOL inventory originally devised for English speaking patients. It consists of a core measure, the 36-item short form health survey (SF-36) previously adapted into Italian, and 18 additional items exploring domains relevant to patients with MS (MS-18 module). The authors translated and culturally adapted into Italian the MS-18 module of the MSQOL-54 questionnaire, and clinically validated the whole questionnaire. METHODS: The MS-18 module was translated following the methodology of the International Quality of Life Assessment (IQOLA) project. The MSQOL-54 was validated in 204 consecutive patients with MS seen between April and September 1997 at three participating centres. The questionnaire was explained by the physician who also administered the expanded disability status scale (EDSS) and mini mental status scale examination, and the patient filled in the MSQOL-54 and Beck depression inventory questionnaires (BDI), with assistance if required. The contribution of impairments and disabilities to MSQOL-54 scores were assessed, and mean scores were compared with normative data for the general Italian population, and with the original sample of United States MS patients. RESULTS: The mean age of the 204 patients was 42 years; mean EDSS score was 4.5 (range 0-8. 5). Patients' participation in the assessment was satisfactory, and all scales satisfied the usual psychometric standards. The characteristics of the United States sample matched those of our patients in all but gender (72% United States patients v 52% Italian patients were women), and education (90% United States patients and 44% Italian patients completed high school); MSQOL-54 profiles were also similar. The EDSS was significantly associated with the physical health composite but not with the mental health composite score. Multiple linear regression modelling showed that age and BDI independently predicted physical health composite (p < 0.001), and mental health composite (p < 0.001). Clinical worsening in the previous year had an independent effect on the physical health composite (p < 0.001). CONCLUSIONS: The Italian version of MSQOL-54 is easy to administer and is well accepted by patients. Neurological impairment has a limited influence on perceived quality of life, while age and depressive symptoms has a major influence.

Physical rehabilitation has a positive effect on disability in multiple sclerosis patients.

BACKGROUND: Although physical rehabilitation is commonly administered to MS patients, its efficacy has not been established. OBJECTIVE: We assessed the efficacy of an inpatient physical rehabilitation program on impairment, disability, and quality of life of MS patients with a randomized, single-blind, controlled trial. METHODS: Fifty ambulatory MS patients were assigned to 3 weeks of inpatient physical rehabilitation (study treatment) or exercises performed at home (control treatment). Patients were evaluated at baseline and at 3, 9, and 15 weeks by a blinded examining physician. RESULTS: No changes in impairment occurred in either group, as measured by the Expanded Disability Status Scale. At the end of the intervention the study group improved significantly in disability, as assessed by the Functional Independence Measure (FIM) motor domain, compared with controls (p = 0.004), and the improvement persisted at 9 weeks (p = 0.001). The effect size statistic was usually large or moderate in all scale scores of the FIM motor domain at 3 weeks and moderate to fair thereafter. The study group also improved in overall health-related quality of life profile compared with controls; however, the difference was significant only for the mental composite score at 3 (p = 0.008) and 9 weeks (p = 0.001). CONCLUSIONS: Despite unchanging impairment, physical rehabilitation resulted in an improvement in disability and had a positive impact on mental components of health-related quality of life perception at 3 and 9 weeks.

Eye-movement disorders and visual-perceptual impairment in diplegic children born preterm: a clinical evaluation.

The visual-motor behaviour of 15 preterm diplegic children and 50 control children (age range 4 to 7 years) was recorded on video as they performed a visual-perceptual task (an adaptation of the Animal House subtest of the Wechsler Preschool Primary Scale of Intelligence). The following parameters were analysed and scored: time to perform task; omissions; figure-colour association; sequence direction; sequential scanning order; accuracy of fitting target; and number of anticipatory saccadic movements to next target. The ability of the control children to perform the task improved significantly with age, as measured by performance time, mistakes in sequence direction and scanning order, accuracy of target fitting, and number of anticipatory saccadic movements. The scores of children with diplegia were not related to age and were poorer overall than those of the control group. Children with diplegia made significantly more mistakes of sequence direction and scanning order, and significantly fewer anticipatory saccadic movements than the control group. These results indicate that visual-perceptual impairment in diplegic children born preterm is not attributable only to sensory visual loss and to fine manipulation difficulties but is also related to difficulties in eye movements and in using anticipatory control to process information.

Incidence and survival of childhood CNS tumours in the Region of Lombardy, Italy.

Incidence rates for CNS tumours in children of age 0-14 years in the Region of Lombardy, Italy, during the period 1988-93 were analysed; survival probability updated to December 1995 was also estimated. CNS tumours defined according to the International Classification of Diseases for Oncology codes were actively searched for. CNS tumours were diagnosed in 296 children. The age-standardized rates were 40.0 per million child years for both sexes together, and 45.3 for boys and 34.4 for girls. In all age groups, boys had a higher incidence than girls. The annual incidences were 13.7, 7.0, 5.8 for astrocytoma, medulloblastoma and ependymoma, respectively. The overall survival percentages at 5 and 8 years after diagnosis were 68 and 66, respectively. Prognosis was good for astrocytoma (5-year survival, 81%), and declined in the order: other gliomas (5-year survival, 76%); ependymoma (5-year survival, 62%), and medulloblastoma (5-year survival, 43%). The histological type of the tumour was the most powerful independent predictor of survival in children with a CNS tumour. Medulloblastoma/primitive neuroectodermal tumours appeared to have the highest risk of a poor prognosis compared with astrocytoma (relative risk, 3.27; 95% confidence interval, 1.81-5.91). Age at diagnosis and sex had no significant effect on survival. The incidence of childhood CNS tumours found in this study is higher than previously reported in Italy, and is one of the highest in the world from population-based data. Survival of children with brain tumours has improved greatly in recent years. These results suggest that children in Lombardy with CNS tumours had a good survival experience compatible with high quality of care.

Parental occupation, occupational exposure to solvents and polycyclic aromatic hydrocarbons and risk of childhood brain tumors (Italy, France, Spain)

The role of parental occupational exposure in childhood brain tumors was investigated in a population-based case-control study grouping 251 cases and 601 controls from three European centers: Milan (Italy), Paris (France), and Valencia (Spain). Parental occupational exposure to solvents and polycyclic aromatic hydrocarbons (PAH) during the five-year period before birth was estimated using a job-exposure matrix developed earlier in the same countries. Odds ratios (OR) of brain tumors for each occupation and occupational exposure were estimated by logistic regression, adjusting for child's age, gender, exposure to tobacco smoke and ionizing radiation, mother's age and years of schooling, and center. The risk of childhood brain tumors rose when fathers worked in agriculture (OR = 2.2, 95 percent confidence interval [CI] = 1.0-4.7) and motor-vehicle-related occupations. In the latter group, the risk increased for primitive neuroectodermal tumors in particular (OR = 2.7, CI = 1.1-6.6). Astroglial tumors were more frequent among children of mothers in health services (OR = 2.2, CI = 1.0-4.9). Paternal exposure to PAHs was associated with an increased, but not dose-related, risk of primitive neuroectodermal tumors (OR = 2.0, CI = 1.0-4.0), and maternal exposure to solvents at a high level was associated with an increased risk of both astroglial (OR = 2.3, CI = 0.9-5.8) and primitive neuroectodermal tumors (OR = 3.2, CI = 1.0-10.3).

Advantage of treating anaplastic gliomas with aggressive protocol combining chemotherapy and radiotherapy.

We devised a treatment protocol for anaplastic gliomas consisting of:(a) chemotherapy prior to radiotherapy (b) a second chemotherapy regimen at tumor recurrence (c) repeated surgery whenever possible. 41 Anaplastic Astrocytoma (AA), 16 Anaplastic oligoastrocytoma (AOA) and 14 anaplastic oligodendroglioma (AOD) patients were treated. After surgery all patients received 5-6 cycles of carmustine+Cisplatinum chemotherapy. Radiotherapy was started during the last 2-3 cycles of chemotherapy. 17 patients (30.5%) were reoperated on at recurrence. All recurring patients underwent PVC chemotherapy. At this moment disease recurred in 56 patients. Median TTP was 24.5, 38.7 and 58.2 months for AA, AOA and AOD respectively. Median ST was 38.8, 71.8 and 73 months. In conclusion our sandwich protocol of prior chemotherapy, overlapping irradiation with second chemotherapy and, in favourable cases, a second surgical intervention, is of benefit in patients with anaplastic gliomas.

MRI features of cerebral lesions and cognitive functions in preterm spastic diplegic children.

The aim of this study is to further clarify the relation between the pattern of cognitive impairment in spastic diplegic children born preterm and MRI features of cerebral lesions. The cognitive profile by Wechsler Scale of a sample of 30 children aged 6 years, 8 months to 14 years, 7 months was assessed, and the correlations between the Full Scale, Verbal, and Performance IQ and periventricular leukomalacia features on MRI were investigated. A significant difference was observed between the mean Verbal and Performance IQ, indicating a specific failure in the visuoperceptual functions of spastic diplegic children born preterm. Periventricular leukomalacia was detected in all children. The severity of ventricular dilatation, the degree and extent of white matter reduction, optic radiation involvement, and the thinning of the posterior corpus callosum correlated significantly with the Full Scale and Performance IQ: no correlation was observed between the Verbal IQ and any of the MRI features analyzed. In spastic diplegic children, an MRI examination between the ages of 1 and 2 years may be helpful in predicting a specific neuropsychological pattern of dysfunction and in defining an early intervention program.

Survival in multiple system atrophy: a study of prognostic factors in 59 cases.

The various clinical features of multiple system atrophy (MSA) make the diagnosis of the disease difficult, especially in its early stages, when signs of differentiated neuroanatomical system involvement have not yet appeared. Mortality studies may be affected by the variability of the diagnostic criteria and selection bias. We used strict clinical and MRI criteria to diagnose MSA in 59 patients. Patients with parkinsonian and cerebellar onset were compared. Median survival time from the onset of the first motor symptom was 7.5 years. Our results indicated a trend (P = 0.09) for the Northwestern University Disability Scale score to correlate with mortality, but we failed to find other characteristics identifying subgroups or predictors for survival.

Possible identification of cervicogenic headache among patients with migraine: an analysis of 374 headaches.

According to Sjaastad, the pain in cervicogenic headache, a form not recognized by the IHS, is long lasting and always side-locked unilateral. The frequency of side-locked unilateral pain (defined here as no change in side from onset) and other characteristics of cervicogenic headache were investigated in 300 outpatients using information collected on standard forms in structured interviews. Three hundred seventy-four headaches diagnosed according to IHS criteria were identified. Three hundred forty-eight of these headaches were long-lasting (duration of more than 4 hours); migraine (65%) followed by tension-type headache (25%) were the commonest forms. Side-locked unilaterality was present in 29% (101 of 348), and occurred most frequently in migrainous disorders not fulfilling the criteria (25 of 56, 44.6%). This group differed significantly from the other migraine conditions for longer pain duration (P < 0.02) and less frequent nausea, vomiting, photophobia, phonophobia (P < 0.0001), and aggravation by physical activity (P < 0.02). With these characteristics, this group resembled cervicogenic headache. However, in none of these patients was pain triggered by head or neck movements, and the frequency of head or neck trauma did not differ from other headaches. A more precise definition of clinical criteria for cervicogenic headache vs migraine is, therefore, required.

Assessment of International Headache Society diagnostic criteria: a reliability study.

In 1988 the International Headache Society (IHS) introduced new diagnostic criteria for headaches and craniofacial pain. Since headaches can be diagnosed solely on the basis of information provided by the patient, it is essential that the criteria are reproducible and consistent. Two neurologists evaluated the clinical records of 100 consecutive outpatients and transferred the data on headache and associated phenomena to a form designed to reflect the IHS criteria. Interobserver concordance (kappa statistics) in the application of the diagnostic criteria of primary headaches was: (i) "perfect" to "substantial" for the first IHS digit, being kappa = 1.0 for cluster headache and paroxysmal hemicrania; kappa = 0.88 for migraine; kappa = 0.75 for tension-type headache; (ii) "almost perfect" to "substantial" for the second digit (kappa = 0.94 for cluster headache; kappa = 0.90 for migraine with aura; kappa = 0.81 for episodic tension-type headache; kappa = 0.78 for migraine without aura; kappa = 0.71 for chronic tension-type headache; kappa = 0.66 for cluster headache-like disorder not fulfilling the criteria; (iii) "moderate" for migrainous disorder (kappa = 0.48) and headache of the tension-type (kappa = 0.43) not fulfilling the criteria. These results show that the IHS diagnostic criteria are satisfactorily applicable to high quality medical records abstracted by experienced neurologists.

Mothers' active and passive smoking during pregnancy and risk of brain tumours in children.

As part of a collaborative study of risk factors for childhood brain tumours, the effects of the mother's smoking and her potential for passive smoking exposure during the pregnancy were assessed in a case-control study. Parents of 91 cases and 321 population controls from Northern Italy, matched for age, sex and residence, were interviewed about their lifetime smoking habits. Mother's smoking during pregnancy was associated with an odds ratio (OR) of 1.7 (95% CI 0.8, 3.8) of brain tumour in her child although this was not statistically significant. Among non-smoking mothers, the risk for light and heavy exposure to passive smoking was 1.7 (0.8, 3.6) and 2.2 (1.1, 4.5) respectively, and a statistically significant dose-response relationship was found (p trend = 0.02). These results must be interpreted within the constraints of the relatively small sample size and the likely misclassification produced by the difference between the potential for exposure to passive smoke and the true exposure. However, they add another piece of information to the growing body of evidence available about the health consequences both of active and of passive smoking and highlight the need for more information about this putative association.

The cognitive development of children born preterm and affected by spastic diplegia.

In a prospective study the intellectual development of 20 premature children affected by spastic diplegia was compared with that of 10 preterm low-risk children. The assessment was carried out with the Griffiths scale at the age of 3 years and with the WPPSI scale at the age of 6 years. The analysis of data collected in the 2 psychometric evaluations of the preterm-born diplegic children showed a disharmonic profile of neuropsychological functions, already present at the age of 3 years and confirmed at the age of 6 years. The average scores in diplegic children were poorest in the subscales locomotor, eye-hand coordination, and performance on Griffiths scale, and in the performance subtests of the WPPSI scale. The mean scores of subscales for hearing and speech, and practical reasoning on the Griffiths scale and of the verbal subscale of the WPPSI were near to the lower range of the normal distribution. Significant differences in performance subtests were found between the groups of preterm diplegic children and the group of low-risk preterm children, both at 3 and 6 years of age.

Thiopental pharmacokinetics in patients with cirrhosis.

The effect of cirrhosis on the pharmacokinetics and plasma protein binding of thiopental was studied in eight patients with cirrhosis, aged (mean +/- SD) 42 +/- 11 yr, and nine patients with normal hepatic and renal function, aged 48 +/- 12 yr, undergoing elective abdominal or orthopedic surgery. The total apparent volume of distribution at steady state was of 2.3 +/- 0.5 1 X kg-1 in the controls and of 3.5 +/- 1.9 1 X kg-1 in the patients with cirrhosis. Thiopental plasma clearance based upon total drug concentrations was 3.9 +/- 1.2 ml X min-1 X kg-1 in the normal group and did not differ significantly in the patients with cirrhosis: 4.4 +/- 2.2 ml X min-1 X kg-1. The elimination half-life was of 529 +/- 97 min in the controls and of 714 +/- 252 min in the patients with cirrhosis. The thiopental free fraction was 14.5 +/- 3.4% in the controls and was increased significantly to 25.2 +/- 3.9% in the patients with cirrhosis. Thiopental intrinsic clearance was decreased insignificantly (P = 0.06) from 28.3 +/- 9.0 ml X min-1 X kg-1 in the controls to 18.2 +/- 10.5 ml X min-1 X kg-1 in those with cirrhosis, suggesting that these patients may have a decreased capacity for thiopental metabolism. These results suggest that the risk of a prolonged effect following thiopental administration appears unlikely in patients with cirrhosis.