Biomedical subjects

W Maixner

Publications and source records attributed to W Maixner.

At least 19 recordsLinked to original sources

PubMed2006

Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure.

Catechol-O-methyltransferase (COMT) is a key regulator of pain perception, cognitive function, and affective mood. Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous position, code for differences in COMT enzymatic activity and are associated with pain sensitivity. Haplotypes divergent in synonymous changes exhibited the largest difference in COMT enzymatic activity, due to a reduced amount of translated protein. The major COMT haplotypes varied with respect to messenger RNA local stem-loop structures, such that the most stable structure was associated with the lowest protein levels and enzymatic activity. Site-directed mutagenesis that eliminated the stable structure restored the amount of translated protein. These data highlight the functional significance of synonymous variations and suggest the importance of haplotypes over single-nucleotide polymorphisms for analysis of genetic variations.

Alleles↗

PubMed2006

Health related quality of life and psychological outcome in patients treated for craniopharyngioma in childhood.

UNLABELLED: Patients with craniopharyngioma are at risk for many adverse effects related to the tumour's invasive behaviour and its proximity to many vital structures. Profound psychosocial problems, memory impairment, pituitary and hypothalamic dysfunction in addition to the physical handicap of visual loss are frequently recognized sequelae of craniopharyngioma treatment. OBJECTIVES: To examine health related quality of life (QoL) and psychological outcomes of patients treated for craniopharyngioma at the Royal Children's Hospital, Melbourne, between January 1980 and September 2003. PATIENTS: Seven (17.4%) of 46 (26 male) had died. Thirty-nine remained, of whom 30 were contactable. Eighteen of 30 (8 male), mean age 21.2 +/- 6.7 years, agreed to evaluation, of whom 16/18 (88.9%) had three or more pituitary hormone deficiencies, 11/18 had visual impairment and 9/18 obesity. MEASUREMENTS: The Adult GH-Deficient Assessment (AGHDA) and Psychological General Well-Being (PGWB) questionnaires were employed to assess quality of life in patients and age- and sex-matched healthy controls. Additional psychological assessment, including intellectual and academic skills, emotional function, and adaptive behaviour, had been undertaken in 12 patients at a previous time. RESULTS: High levels of physical morbidity and psychological disability were described. The General Health score of patients was significantly worse than for controls on PGWB (p = 0.025), anxiety was higher in those who had surgery alone (p = 0.008) and subjective QoL associated with GHD using AGHDA was lower (p = 0.006). Few craniopharyngioma survivors (18/30) were available for evaluation, demonstrating difficulties in attempts to assess this complex group. The discrepancy between results of objective and subjective measures of QoL is discussed in terms of adaptation to illness, disabilities and changed perception of life fulfilment. CONCLUSIONS: Craniopharyngioma and its treatment result in significant, complex medical, social, psychological and emotional difficulties. The degree of global disability is not reflected in subjective QoL reports for this group, highlighting the need for careful selection of assessment instruments.

Activities of Daily Living↗

PubMed2003

Increased perception of post-ischemic paresthesias in depressed subjects.

A psychophysical assessment of sensory activity linked to unmyelinated and myelinated primary afferents was conducted by estimating the intensity of thermal and tactile post-ischemic paresthesias in 11 nontreated depressed subjects (Zung's index > or =50) and 19 controls. Blood flow in the dominant forearm was arrested until ischemic pain tolerance was reached. Ischemic pain and post-ischemic paresthesias were numerically rated. The duration of blood flow occlusion to the time of ischemic pain tolerance was similar in both groups. Thermal (warm/cool) and tactile (tingling) paresthesias were 96% and 57% more intense in depressed than in control subjects, respectively. Zung's depression scores were positively correlated with the tingling and thermal paresthesias. Ischemic pain intensity correlated positively with thermal paresthesias. These findings suggest that depression is associated with enhanced sensory paresthesias that are known to be predominately linked to unmyelinated afferent activity.

Adult↗

PubMed2001

Lack of effect of ondansetron on the pharmacokinetics and analgesic effects of morphine and metabolites after single-dose morphine administration in healthy volunteers.

AIMS: The purpose of this investigation was to study the influence of ondansetron on the single-dose pharmacokinetics and the analgesic effects elicited by morphine and the 3- and 6-glucuronide metabolites of morphine in healthy volunteers. METHODS: This was a randomized, double-blind, placebo-controlled, two-way crossover study in which six male and six female subjects were administered a single 10 mg intravenous dose of morphine sulphate, followed 30 min later by a single 16 mg intravenous dose of ondansetron hydrochloride or placebo. Serum and urine concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) samples were quantified over 48 h using high performance liquid chromatography with detection by mass spectrometry. Analgesia was assessed in the volunteers with a contact thermode device to provide a thermal pain stimulus. Four analgesic response variables were measured including thermal pain threshold, thermal pain tolerance, temporal summation of pain and mood state. RESULTS: The two treatments appeared to be equivalent based on the 90% confidence intervals (0.6, 1.67) of the least squares means ratio. All least squares means ratio confidence intervals for each parameter, for each analyte fell within the specified range, demonstrating a lack of an interaction. CONCLUSIONS: The results of this study suggest that administration of ondansetron (16 mg i.v.) does not alter the pharmacokinetics of morphine and its 3- or 6-glucuronide metabolites to a clinically significant extent, nor does it affect the overall analgesic response to morphine as measured by the contact thermode system.

Adolescent↗

PubMed2001

Effects of systemic morphine on escape latency and a hindlimb reflex response in the rat.

The present study uses focal electrical stimulation of myelinated nociceptors to simultaneously assess behavioral responses that are organized at spinal and supraspinal sites in the rat. Hindlimb reflex amplitude and the latency to operant escape responses by a forelimb were recorded for each stimulus presentation to a hindlimb across a wide range of intensities. This paradigm provided a tool whereby effects of morphine on conscious escape responses could be delineated from effects on a segmental flexion reflex over a range of doses. Administration of morphine (3 mg/kg and 10 mg/kg, subcutaneously) increased the latency of escape responses and decreased the amplitude of reflex responses in a dose-dependent manner. However, morphine produced a greater suppression of reflex responses compared with the increase in effects on escape latencies. The effects of morphine on escape latency were not expressed at the highest stimulus intensities (0.6 to 0.8 mA), whereas reflex responses were attenuated at all suprathreshold stimulus intensities. Thus, electrically evoked, spinal-mediated responses of rats are not affected by morphine in the same manner as electrically evoked supraspinal-mediated nociceptive behaviors. However, both measures confirm evidence that responses elicited by activation of myelinated afferents are less powerfully affected by morphine than responses to input from unmyelinated nociceptors.

Journal Article↗

PubMed2001

The effects of noxious dental heating on the jaw-opening reflex and trigeminal Fos expression in the ferret.

Previous studies have established that the activation of peripheral nociceptors alters the central processing of nociceptive stimuli. In this study, we examined whether noxious heating of the dental pulp enhances the nociceptive jaw-opening reflex (JOR) and the expression of the immediate early gene c-fos in chloral hydrate/pentobarbital-anesthetized ferrets. We hypothesized that the application of noxious heat to the dental pulp, a procedure that evokes a preferential activation of pulpal C-fibers, will enhance JOR responses to electrical stimulation of the tooth pulp and that this enhanced response will be associated with the expression of Fos protein in discrete regions of the trigeminal nucleus. Consistent with our predictions, we observed that noxious heat conditioning enhanced the JOR as indicated by an increase in the magnitude of the signal averaged digastric electromyogram response evoked by electrical stimuli applied to either a heat-conditioned maxillary canine or the contralateral nonconditioned canine. The enhancement in JOR responses was independent of temporal summation of the electrical stimulus for test stimuli delivered at either 1.0 or 0.1 Hz. Sensitization of the JOR was associated with an increase in the number of immunohistochemically identified Fos-positive nuclei in trigeminal caudalis (Vc) and the transition zone between trigeminal interpolaris and caudalis (Vi/Vc) ipsilateral to the site of stimulation compared with sham stimulated animals. These findings suggest that neuronal populations in Vc and Vi/Vc play a role in the enhanced reflex responses to tooth pulp stimulation and may contribute to the pain and hyperalgesia associated with a symptomatic pulpitis.

Journal Article↗

PubMed2001

Long-lasting inflammation and long-term hyperalgesia after subcutaneous formalin injection into the rat hindpaw.

Subcutaneous formalin injection is widely used as a nociceptive stimulus in the rat. This procedure evokes overt behaviors that last about 90 minutes. However, little is known about the duration of paw inflammation and alterations in pain sensitivity to noxious stimuli after 2 hours. We studied the nociceptive responses to thermal and mechanical stimuli 2 hours to 4 weeks after formalin injection into the dorsal or plantar side of the hindpaw. Thirty-two adult male Sprague-Dawley rats were divided into 3 groups: In group I, 50 microL of 5% formalin was injected into the plantar side (n = 12); in group II, 50 microL of 5% formalin was injected into the dorsal side (n = 12); in group III, 50 microL saline was injected into the dorsal or plantar side of the hindpaw (n = 8). Nociceptive responses to thermal and mechanical stimuli applied to the dorsal or plantar surfaces of the injected and the contralateral hindpaws were recorded. The injection of formalin into the rat's hindpaw produced a hypoalgesic region around the injection site. In contrast, hyperalgesic responses to thermal and mechanical stimulation were induced on the opposite surface of the injected hindpaw as well as in the contralateral noninjected hindpaw. The hyperalgesic responses, which were observed 2 hours after formalin administration, were enhanced 1 to 3 days after injection and lasted 3 to 4 weeks. These results suggest that peripheral inflammation after subcutaneous formalin injection produces a long-lasting sensitization. Possible mechanisms for these changes in nociception are discussed.

Journal Article↗

PubMed2001

Sex differences in chest pain in patients with documented coronary artery disease and exercise-induced ischemia: Results from the PIMI study.

BACKGROUND: Sex differences in the pathophysiologic course of coronary artery disease (CAD) are widely recognized, yet accurate diagnosis of coronary artery disease in women remains challenging. METHODS: To determine sex differences in the clinical manifestation of CAD, we studied chest pain reported during daily activities, exercise, and mental stress in 170 men and 26 women. All patients had documented CAD (>50% narrowing in at least 1 major coronary artery or prior myocardial infarction) and all had 1-mm ST-segment depression on treadmill exercise. We collected psychologic test results, serum samples (potassium, epinephrine, norepinephrine, cortisol, b-endorphin, and glucose), and cardiac function, sensory threshold, and autonomic function data at specified times before, during, or after exercise and mental stress tests to assess measures of depression, anxiety, and neurohormonal and thermal pain perception. RESULTS: Women reported chest pain more often than men during daily activities (P =.04) and during laboratory mental stressors (P =.01) but not during exercise. Men had lower scores than women on measures of depression, trait anxiety, harm avoidance, and reward dependence (P <.05 for all). Women had significantly lower plasma b-endorphin levels at rest (4.2 +/- 3.9 vs 5.0 +/- 2.5 pmol/L for men, P =.005) and at maximal mental stress (6.4 +/- 5.1 vs 7.4 +/- 3.5 pmol/L for men, P <.01). A higher proportion of women than men had marked pain sensitivity to graded heat stimuli applied to skin (hot pain threshold <41 degrees C, 33% vs 10%, P =.001). CONCLUSIONS: Our results reflect sex differences in the affective and discriminative aspects of pain perception and may help explain sex-related differences in clinical presentations.

Activities of Daily Living↗

PubMed2000

Long-lasting delayed hyperalgesia after subchronic swim stress.

Rats subjected to an inescapable subchronic stress, consisting of 10-20 min of forced swimming for 3 days, showed a thermal hyperalgesia and an enhanced nociceptive behavior to the subcutaneous administration of formalin 24 and 48 h, respectively, after the last swim session. Hyperalgesia to thermal and chemical stimulants was still present 8 and 9 days after the last swim session, respectively. Chemical, but not thermal, nociception was negatively correlated with the swim effort or struggle times during the last swim session. The serotonin-selective reuptake inhibitors clomipramine (2.5 mg/kg/day, i.p., started 3 or 7 days before stress) and fluoxetine (0.25 mg/kg/day, i.p., started 7 days before stress), or serotonin precursor tryptophan (3 mg/kg/day, i.p., 24 h before each swim stress) blocked the development of both the thermal and the chemical hyperalgesia and increased swim effort times compared to vehicle-treated rats. These treatments did not affect nociceptive responses in control rats subjected to sham swimming. These findings suggest that repeated stress can produce a long-lasting increase in pain sensitivity to both phasic or tonic noxious stimuli by diminishing central serotonin activity. This model may help elucidate the underlying neural mechanisms that mediate the effects of repeated stress on pain sensitivity and affective states.

Animals↗

PubMed2000

Relationship between nociceptor activity, peripheral edema, spinal microglial activation and long-term hyperalgesia induced by formalin.

To determine whether initial nociceptive inputs caused by subcutaneous injection of formalin into the hindpaw are necessary and/or sufficient for allodynic behavior and microglial activation observed at one week following behavior, we examined Sprague-Dawley rats under five test conditions. Test condition 1. Formalin alone group (six rats), 5% formalin was injected subcutaneously into the dorsal side of the right hind paw. Test condition 2. Bupivacaine/Formalin group (six rats), bupivacaine was injected into the ankle area and into the site of formalin injection 10 min before formalin injection. Test condition 3. Saline/Formalin group (six rats), saline was injected 10min before formalin in the same manner as bupivacaine. Test condition 4. Formalin/Bupivacaine group 1 (six rats), bupivacaine was injected 10 min after formalin. Test condition 5. Formalin/Bupivacaine group 2 (six rats), bupivacaine was injected similarly 1h after formalin. The magnitude of paw edema and paw withdrawal thresholds to mechanical stimuli applied to the plantar surface of the injected paw and on the dorsal surface of the contralateral side were evaluated prior to and one week after formalin injection. The lumbar spinal cord was immunohistochemically processed at one week to assess the expression of a marker for activated microglia. The results showed: (i) pre-treatment with bupivacaine blocked both phases of formalin-evoked pain behaviors and the mechanical allodynia that developed one week post-formalin injection, but did not block microglial activation; (ii) treatment with bupivacaine 1h after formalin injection reduced paw edema and prevented skin ulceration, but one week allodynia and microglial activation were still present; and (iii) prolonged spinal microglial activation was not dependent on acute formalin-induced nociceptor activity, but was strongly associated with the amount of tissue destruction. Our studies suggest that: (i) the central sensitization associated with the phase II of formalin-evoked behaviors and spinal microglial activation are both necessary to permit the development of the long-term hyperalgesia produced by the subcutaneous administration of formalin into the rat's hindpaw; and (ii) acute nociceptive inputs following formalin injection are not necessary for central microglial activation that may be triggered by nerve damage or prolonged signals from peripherally inflamed tissue

Anesthetics, Local↗

PubMed1999

Microglial reactions after subcutaneous formalin injection into the rat hind paw.

Microglia in primary afferent projection territories are activated and proliferate after peripheral nerve injury. However, it is not known whether stimulation of peripheral nerves by noxious stimuli applied to their receptive fields activates microglial cells in the spinal cord. This study was designed to investigate the response of microglia in the lumbar spinal cord and in the brainstem to a tonic noxious stimulus. Thirty-two male Sprague-Dawley rats received subcutaneous injections of 5% formalin (50 microliter) into the plantar surface of the right hind paw, and 24 rats were injected with 50 microliter saline as a control. The lumbar spinal cord and brainstem were evaluated for immunoreactivity (IR) to complement receptor C3bi (monoclonal antibody OX-42) and major histocompatibility complex class II (monoclonal antibody OX-6) on postinjection hours 0, 2, 4 and 8 and days 1, 3, 7, 14 and 28. A qualitative and quantitative increase of OX-42-IR microglial cells were observed in the medial portion of the dorsal horn and in the gracile nucleus of the brainstem on the side ipsilateral to the formalin injection, starting on days 1-3 and peaking on day 7 postinjection. OX-6-positive cells were scattered both in gray and white matter, but no difference was detected between the two sides of the spinal cord or between formalin-injected and control animals. This is the first study that reports that subcutaneous injection of formalin into the rat's hind paw induces microglial activation in the spinal cord as well as in the brainstem. Although we have not determined whether these responses result from nociceptor activity, peripheral inflammation, or degeneration of primary afferents and/or central neurons, this method provides a simple, effective and stable animal model that will permit the future study of the mechanisms that contribute to microglial activation and its pathophysiological consequences.

Animals↗

PubMed1999

Dynorphin A increases substance P release from trigeminal primary afferent C-fibers.

Dynorphin A-(1-17) has been found to produce spinal antianalgesia and allodynia. Thus, we studied whether dynorphin A-(1-17) modulates substance P release evoked by the C-fiber-selective stimulant capsaicin (1 microM) from trigeminal nucleus caudalis slices. Very low concentrations of dynorphin A-(1-17) (0.01-0.1 nM) strongly facilitated capsaicin-evoked substance P release. This dynorphin A-(1-17) effect was not blocked by the opioid receptor antagonists naloxone (100 nM), beta-funaltrexamine (20 nM), naloxonazine (1 nM), nor-binaltorphimine (3 nM) and ICI 174,864 (N,N-dialyl-Tyr-Aib-Phe-Leu; 0.3 microM). Yet, the effect of dynorphin A-(1-17) was blocked by the NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5-10-imine maleate; 0.3 microM). Neonatal treatment with capsaicin (50 mg/kg s.c.), which destroys substance P-containing primary afferents, abolished the excitatory effect of dynorphin A-(1-17) on K+-evoked substance P release. In conclusion, dynorphin A-(1-17) increases substance P release from C-fibers by the activation of NMDA receptors which supports the involvement of presynaptic mechanisms in dynorphin-induced antianalgesia and allodynia.

Animals↗

PubMed1999

Reduced tolerance and cardiovascular response to ischemic pain in minor depression.

BACKGROUND: A paradoxical association between a higher prevalence of clinical pain and a reduced sensitivity to brief experimental pain seems to exist during depression. METHODS: We assessed the responses to sustained ischemic pain produced by a maximal effort tourniquet procedure in 32 controls and 11 individuals with minor depression (Zung autoscale > or =50). Stethoscopic blood pressures and heart rates were monitored throughout the procedure. RESULTS: Measures of pain threshold, and measures of pain intensity and pain unpleasantness during the ischemic procedure were similar in depressed and control subjects. Yet, the overall numerical ratings of ischemic pain during the procedure was 28% higher and pain tolerance was 44% lower in depressed compared to control subjects. Clinical pain complaints were reported by 91% of depressed but only by 41% of control subjects (P = 0.01). Sustained ischemic pain induced significant elevations of systolic and mean arterial blood pressures in controls but not in depressed subjects. LIMITATIONS: The main limitation of the present study was the preponderance of females in the depressed group. Yet, we did not find significant gender differences in the sensory-affective and autonomic responses to ischemic pain in our sample. CONCLUSIONS: These findings suggest alterations in the sensory and autonomic nervous systems during minor depression.

Adult↗

PubMed1999

Opposite modulation of capsaicin-evoked substance P release by glutamate receptors.

Substance P and glutamate are present in primary afferent C-fibers and play important roles in persistent inflammatory and neuropathic pain. In the present study, we have examined whether activation of different glutamate receptor subtypes modulates the release of substance P evoked by the C-fiber selective stimulant capsaicin (1 microM) from rat trigeminal nucleus slices. The selective NMDA glutamate receptor agonist L-CCG-IV (1-10 microM) enhanced capsaicin-evoked substance P release about 100%. This facilitatory effect was blocked by 0.3 microM MK-801, a selective NMDA receptor antagonist. The metabotropic glutamate receptor agonists L-AP4 (group III) and DHPG (group I) (30-100 microM) inhibited capsaicin-evoked substance P release by approximately 60%. These inhibitory effects were blocked by the selective metabotropic glutamate receptor antagonist (+/-)-MCPG (5 microM). On the other hand, AMPA and kainate (0.1-10 microM), did not significantly affect capsaicin-evoked substance P release. Thus, substance P release from non-myelinated primary afferents, and possibly nociception, may be under the functional antagonistic control of some metabotropic and ionotropic glutamate receptor subtypes.

Afferent Pathways↗

PubMed1999

Low hot pain threshold predicts shorter time to exercise-induced angina: results from the psychophysiological investigations of myocardial ischemia (PIMI) study.

OBJECTIVES: The purpose of this study was to test whether cutaneous thermal pain thresholds are related to anginal pain perception. BACKGROUND: Few ischemic episodes are associated with angina; symptoms have been related to pain perception thresholds. METHODS: A total of 196 patients with documented coronary artery disease underwent bicycle exercise testing and thermal pain testing. The Marstock test of cutaneous sensory perception was administered at baseline after 30 min of rest on two days and after exercise and mental stress. Resting hot pain thresholds (HPTs) were averaged for the two baseline visits and divided into two groups: 1) average HPT <41 degrees C, and 2) average HPT > or =41 degrees C, to be clearly indicative of abnormal hypersensitivity to noxious heat. RESULTS: Patients with HPT <41 degrees C had significantly shorter time to angina onset on exercise testing than patients with HPT > or =41 degrees C (p < 0.04, log-rank test). Heart rates, systolic blood pressure and rate-pressure product at peak exercise were not different for the two groups. Resting plasma beta-endorphin levels were significantly higher in the HPT <41 degrees C group (5.9+/-3.7 pmol/liter vs. 4.7+/-2.8 pmol/liter, p = 0.02). Using a Cox proportional hazards model, patients with HPT <41 degrees C had an increased risk of angina (p = 0.03, rate ratio = 2.0). These differences persisted after adjustment for age, gender, depression, anxiety and history of diabetes or hypertension (p < 0.01). CONCLUSIONS: Occurrence of angina and timing of angina onset on an exercise test are related to overall hot pain sensory perception. The mechanism of this relationship requires further study.

Adult↗

PubMed1999

Multiphasic morphine modulation of substance P release from capsaicin-sensitive primary afferent fibers.

Morphine produces a multiphasic modulation of K+-evoked substance P release from trigeminal slices and dorsal root ganglion neurons in culture. We now found that the C-fiber stimulant, capsaicin (1 microM), evoked release of substance P that was inhibited, enhanced and inhibited by 0.1 nM, 1 microM, and 10 microM morphine, respectively. This morphine's multiphasic effect was blocked by naloxone (100 nM). Neonatal treatment with capsaicin produced thermal hypoalgesia and abolished the multiphasic effect of morphine on substance P release evoked by 50 mM K+. These findings suggest that the multiphasic modulation of substance P release by morphine is dependent on C-type afferents and may be of relevance to nociception.

Animals↗

PubMed1999

Effects of gender and acute dental pain on thermal pain responses.

OBJECTIVE: Considerable research suggests that females exhibit greater sensitivity to laboratory pain procedures than do males; however, whether the presence of acute clinical pain influences this sex difference in pain sensitivity has not been investigated. The present experiment investigated the effects of sex and acute dental pain on laboratory pain responses. DESIGN: Thermal pain onset and tolerance were determined in 46 dental patients (15 male, 31 female) experiencing pain due to acute irreversible pulpitis and in 33 healthy controls (13 male, 20 female). In addition, measures of mood and coping were obtained in all participants. All subjects participated in two experimental sessions. The first session took place immediately before the patients underwent endodontic treatment for relief of pulpal pain. The second session took place approximately 1-2 weeks later, when pulpitis patients were pain free after treatment. During each session, thermal pain onset and tolerance were assessed with a 1-cm2 contact thermode applied to the right volar forearm using an ascending method of limits. RESULTS: During both sessions, thermal pain onset and tolerance were lower in control females than in control males; however, male and female pulpitis patients did not differ in their thermal pain responses during either session. Pulpitis patients also showed greater affective distress than controls. CONCLUSIONS: These data suggest that the sex difference in thermal pain sensitivity frequently reported in pain-free subjects appears to be absent in patients presenting with acute dental pain. However, this effect cannot be explained solely based on the presence of clinical pain because the effect on pain threshold and tolerance persisted into session 2, when pulpitis patients were pain free. Potential explanations for these results are discussed.

Acute Disease↗

PubMed1999

Benign cerebellar astrocytomas in children.

OBJECT: Cerebellar astrocytomas are benign tumors of childhood known to be associated with excellent long-term survival in patients in whom complete surgical resection is possible. However, the roles of other factors--clinical, radiological, histological, and therapeutic--in the survival of the patient, tumor recurrence, and long-term patient outcome remain imprecise. The goal of this study was to examine these factors and their relationships. METHODS: To clarify these issues a retrospective review was conducted of 168 children who were surgically treated for a cerebellar astrocytoma at Hôpital Necker-Enfants Malades between 1955 and 1995. These patients' clinical files were examined, the histological characteristics of their tumors were reviewed, and their outcomes were assessed according to Bloom's scale and the Wechsler intelligence quotient test. Of the 168 patients in the study, 91 were male and 77 were female with a mean age of 6.9 years and a mean follow up lasting 7.7 years. Tumors were identified as being strictly located in the cerebellum in 76.2% of the patients and as involving the brainstem (referred to as the "transitional form") in 23.8% of the patients. Complete surgical excision was possible in 88.7% of cases. There was a total mortality rate of 4.2% and a tumor recurrence rate of 9.5%. Fifty-eight percent of the patients had no neurological sequelae at follow-up evaluation. Pejorative factors that were discovered by multivariate analysis to be important included: a long preoperative duration of symptoms and the transitional form of tumor with respect to survival; incomplete tumor excision with respect to an increased risk of recurrence; and a long preoperative duration of symptoms, an early epoch during which surgery was performed (1955-1974), severe ventricular dilation, and the transitional form of tumor with respect to a poorer long-term patient outcome. CONCLUSIONS: The presence of brainstem involvement (tumor in the transitional form) emerged as a significant negative prognostic factor and should be treated as a distinct nosological entity. The extent of surgical excision has a significant bearing on the risk of tumor recurrence.

Adolescent↗