Brain magnetic resonance imaging of siblings from families with two or more children with learning or intellectual disabilities and need for full-time special education.

BACKGROUND: Several factors are involved in determining a child's need for special education (SE). Thus, the value of brain magnetic resonance imaging (MRI) for subjects with learning and intellectual disabilities is uncertain. PURPOSE: To evaluate the usefulness of MRI in the diagnostic process of siblings with learning and intellectual disabilities and need for full-time SE. MATERIAL AND METHODS: Altogether, 119 siblings (mean age 11.9 years) from families in which two or more children attended/had previously attended full-time SE underwent prospective brain MRI. SE grouping included three levels, from specific learning disabilities (level 1) to global intellectual disabilities (level 3). Forty-three controls (level 0, mean age 12.0 years) attended mainstream education groups. Signal intensity and structural abnormalities were analyzed, and areas of the cerebrum, posterior fossa, corpus callosum, vermis and brain stem, and diameters of the corpus callosum were measured. In analyses, all area measurements were calculated in proportion to the total inner skull area. RESULTS: Abnormal finding in MRI was more common for siblings (n=62; 52%) in SE (58% for level 3; 49% for level 2; 35% for level 1) than for controls (n=13; 16%). The siblings showed enlarged supra- (P<0.001) and infratentorial (P=0.015) cerebrospinal fluid (CSF) spaces and mild corpus callosum abnormalities (P=0.003) compared to controls. Siblings in SE had smaller inner skull area than controls (P<0.001). Further, the relative area of the mesencephalon (P=0.027) and the diameter of the body of the corpus callosum (P=0.015) were significantly smaller than in controls. In binary logistic regression analysis, enlarged supratentorial CSF spaces increased the probability of SE (odds ratio 4.2; P=0.023). CONCLUSION: Subjects with learning and intellectual disabilities commonly have more MRI findings than controls. Enlarged supratentorial CSF spaces were a frequent finding in siblings in full-time SE.

Two brothers with macrocephaly, progressive cerebral atrophy and abnormal white matter, severe mental retardation, and Lennox-Gastaut spectrum type epilepsy: an inherited encephalopathy of childhood?

Two brothers with severe mental retardation of unknown origin were found to share several physical anomalies, including large round head, small concave nose, downslanted palpebral fissures, and gingival hyperplasia. In addition to relative macrocephaly, magnetic resonance imaging (MRI) showed severe cerebral atrophy, especially fronto-temporally. The brothers also had a thin corpus callosum and atrophic caudate nuclei. The reduced white matter showed patchy periventricular signal intensity changes. The lateral and third ventricles were large, but the fourth ventricle was of normal size. The boys had large cisterna magna, communicating widely with the fourth ventricle, but no vermian hypoplasia. Both boys had Lennox-Gastaut spectrum type epilepsy. No chromosomal anomalies were found, despite the suggestive clinical picture. Some of the clinical findings resembled fetal alcohol effects/fetal alcohol syndrome (FAE/FAS), which was also suggested by history. Current diagnostic criteria for FAE/FAS, however, excluded full-blown FAS in these cases and failed to explain the entire clinical picture in the boys. We argue that these boys had an unidentified inherited syndrome, possibly modified by fetal alcohol exposure.

The safety and efficacy of cisatracurium 0.15 mg.kg(-1) during nitrous oxide-opioid anaesthesia in infants and children.

We studied the neuromuscular and cardiovascular effects of a single, rapidly administered intravenous dose of cisatracurium 0.15 mg.kg(-1) in 27 infants (aged 1-23 months) and 24 children (aged 2-12.5 years). After midazolam premedication, anaesthesia was induced and maintained with thiopental and alfentanil in addition to nitrous oxide in oxygen. Neuromuscular function was monitored by evoked adductor pollicis electromyography. At least 15 min after intubation, each patient received cisatracurium 0.15 mg.kg(-1) over 5 s. Complete neuromuscular blockade was produced by this dose in all but one infant. The mean (SD) onset time of maximal blockade was more rapid in infants [2.0 (0.8) min] than in children [3.0 (1.2) min], p = 0. 0011. The clinical duration of action of cisatracurium (recovery of evoked response to 25% of control) was significantly longer in infants [43.3 (6.2) min] than in children [36.0 (5.4) min], p < 0.0001. Once neuromuscular function started to recover, the rate of recovery was similar in both age groups. Changes in blood pressure and heart rate after the administration of cisatracurium were negligible in both age groups. Cisatracurium, at a dose of 0.15 mg. kg(-1), was effective and well tolerated in infants and children.

A dose-ranging study of rapacuronium in pediatric patients.

BACKGROUND: The aim of this study was to determine the dose or doses of the new rapid-onset, short-acting, neuromuscular blocking drug rapacuronium that would provide satisfactory conditions for tracheal intubation at 60 s in infants and children. METHODS: Sixty-five infants (< 1 yr), 51 younger children (1-6 yr), and 49 older children (7-12 yr) were studied. Anesthesia was induced with thiopental-nitrous oxide-oxygen. Tracheal intubation was attempted 60 s after administration of one of five doses of rapacuronium (0.5, 1.0, 1.5, 2.0, or 2.5 mg/kg) and intubating conditions were assessed using a four-point scale. Following tracheal intubation, anesthesia was maintained with nitrous oxide-oxygen and alfentanil (12.5-50 microg/kg) as necessary. Neuromuscular transmission was monitored in an uncalibrated fashion using an acceleromyograph. RESULTS: Intubating conditions were good or excellent at 60 s in all infants after doses of 1.5 mg/kg or more and in all younger and older children after doses of 2.0 mg/kg or more. The duration of action of rapacuronium was dose- and age-dependent. Mean times to reappearance of the third twitch of the train-of-four (TOF; T3) were less than 10 min in infants at doses of 1.5 mg/kg or less and in younger and older children at doses of 2.0 mg/kg or less. Recovery of T3 after 1.0-2.0 mg/kg rapacuronium was significantly slower in infants compared with younger (P = 0.001) and older (P = 0.02) children. Five adverse experiences were related to rapacuronium administration: Bronchospasm (two instances), tachycardia (one instance), and increased salivation (two instances). None were serious. CONCLUSIONS: Doses of 1.5 and 2.0 mg/kg rapacuronium can produce satisfactory intubating conditions at 60 s in anesthetized infants and children, respectively, and are associated with a short duration of action.

Bone marrow transplantation in aspartylglucosaminuria--histopathological and MRI study.

This study comprised two patients with aspartylglucosaminuria (AGU), who were followed up for 4 and 7 years. The patients underwent allogeneic bone marrow transplantation (BMT) at the ages of 2 and 2.6 years. Both patients had abnormal speech development and gross motor clumsiness. At the time of the BMT, they were mentally retarded. We report on follow-up data of these patients obtained by MRI, in addition to the histopathological, biochemical and clinical investigations. MR images of six non-transplanted patients and seven healthy children served as controls. In the non-transplanted patients, MRI revealed evident delay of myelination in contrast to the two transplanted patients showing fair or evident grey- vs. white matter differentiation on T2-weighted images. The aspartylglucosaminidase (AGA) activity in blood leukocytes reached a heterozygous level. Urinary excretion of aspartylglucosamine and glycoasparagines slowly decreased but remained about a third of the pre-BMT level 5 years after BMT. Storage lysosomes in electron microscopic investigations were not decreased 6 months after BMT, but after 1.5-2 years, rectal mucosa samples showed a decrease in the storage vacuoles of different cells. Three years after BMT, no cells with storage vacuoles were present. Allogeneic BMT slowly normalises the pathological, biochemical and MRI findings in patients with AGU.

Aspartylglucosaminuria: radiologic course of the disease with histopathologic correlation.

Twelve living patients (aged 19 months to 32 years) with aspartylglucosaminuria were examined by magnetic resonance imaging (MRI), and the magnetic resonance (MR) images of 16 health volunteers (aged 4 to 32 years) were used as controls. One patient was examined twice. Postmortem MRI and histopathologic analysis were done on the brains of four additional adult patients. Signal intensities determined quantitatively on T2-weighted images differed significantly between patients and controls, being higher from the white matter (P < .0002) and lower from the thalami (P < .03) in the patients. The generally increased signal intensity of the white matter was most obvious in the young patients, with many focal areas of very high signal intensity in the subcortical white matter. The subcortical white matter showed a somewhat increased signal intensity even at the age of 32 years. In two of the four postmortem MR images, the distinction between the gray and white matter was still poor. At histopathologic analysis, the basic cortical cytoarchitecture was generally preserved but most neurons contained vacuoles, which were also found in the neurons of the deep gray matter. In two of the four autopsy cases the white matter showed diffuse pallor of myelin staining and some gliosis. Thus aspartylglucosaminuria is primarily a gray-matter disease also affecting white matter by delaying myelination.

Sevoflurane-nitrous oxide or halothane-nitrous oxide for paediatric bronchoscopy and gastroscopy.

We have studied 120 infants and children, in three age groups (3-11 months, 1-5 yr and 6-15 yr), to compare anaesthesia with sevoflurane or halothane for bronchoscopy or gastroscopy, or both. Premedication or i.v. anaesthetic agents were not used. Patients were allocated randomly to receive either 7% sevoflurane or 3% halothane in 66% nitrous oxide in oxygen for induction of anaesthesia. The same inspired mixture was continued during bronchoscopy while the concentration of the inhalation agent was reduced by 50% during gastroscopy. Induction times were shorter for infants than for children and shorter for sevoflurane than for halothane. Cardiac arrhythmias were significantly more frequent during halothane than during sevoflurane anaesthesia. Physiological and psychomotor recovery were more rapid after sevoflurane than after halothane. At 24-h follow-up, children who received sevoflurane had significantly less nausea and vomiting. We conclude that sevoflurane was superior to halothane for paediatric bronchoscopy and gastroscopy.

Time course of potentiation of mivacurium by halothane and isoflurane in children.

We studied 40 children, aged 1-15 yr, to analyse the time course of potentiation of mivacurium produced by halothane and isoflurane. A steady infusion requirement of mivacurium to maintain 90% neuromuscular block was established during thiopentone-alfentanil-nitrous oxide-oxygen anaesthesia. Patients were then allocated randomly to receive 1 MAC end-tidal concentration of either halothane (group Hal) or isoflurane (group Iso) while neuromuscular block was maintained at 90%. Both volatile agents decreased the infusion requirements of mivacurium in an exponential manner in that maximal potentiation occurred only after 30-80 min. Maximal reduction in infusion rate (32% in group Hal and 70% in group Iso; P < 0.0001) did not depend on the age of the child but became established sooner the younger the child in the case of isoflurane (P = 0.002).

Cisatracurium during halothane and balanced anaesthesia in children.

Cisatracurium, 51W89, is one of the ten stereoisomers of Tracrium which, unlike atracurium, has been reported to have a lack of histamine mediated cardiovascular effects at doses as high as 8 x ED95 in adults. We compared the time-course of neuromuscular effects of 80 micrograms.kg-1 or 100 micrograms.kg-1 cisatracurium during N2O-O2-halothane or N2O-O2-opioid anaesthesia, respectively, in 32 children 2-12 years old. Neuromuscular function was monitored by evoked adductor pollicis EMG. Even-numbered patients (n = 16) were allowed to obtain full spontaneous recovery of neuromuscular function and odd-numbered patients (n = 16) received neostigmine 45 micrograms.kg-1 together with glycopyrrolate at the time of 25% EMG recovery. Data are expressed as median with 10th to 90th percentile range. Cisatracurium had an onset time (time from administration to maximal effect) of 2.2 (1.7-3.8) or 2.3 (1.8-4.9) min, a clinical duration (time to 25% EMG recovery) of 34 (22-40) or 27 (24-33) min, and a spontaneous 25-75% recovery time (time from 25 to 75% EMG recovery) of 11 (9-13) or 11 (7-12) min during halothane or balanced anaesthesia, respectively (NS). Train-of-four ratio recovered to 0.70 in 2.5 (1.8-3.0) or 3.2 (2.1-4.3) min following neostigmine during halothane or balanced anaesthesia, respectively (NS). Changes in blood pressure or heart rate following cisatracurium were negligible. We regard cisatracurium as a safe and promising intermediate duration muscle relaxant the effects of which can easily be reversed with neostigmine.

Reversal of atracurium-induced neuromuscular block in paediatric patients.

We studied the efficacy of neostigmine and edrophonium to reverse an atracurium-induced 90% neuromuscular block in 80 paediatric patients anaesthetized with thiopentone, fentanyl and nitrous oxide. The patients were divided into five age groups: 0-2 months, 3-11 months, 2-5 years, 6-10 years, and 11-15 years. At the end of surgery, the neuromuscular block was randomly antagonized with either neostigmine 50 micrograms kg-1 with atropine 20 micrograms kg-1 or with edrophonium 1 mg kg-1 with atropine 10 micrograms kg-1. In general, the first EMG response and train-of-four (TOF) ratio recovered fastest in the youngest age groups following either reversal agent (P < 0.05). However, in each age group edrophonium had a faster onset of effect than neostigmine (P < 0.05) even though a greater TAO-ratio was finally reached with neostigmine. The effects of neostigmine were less variable and more predictable than those of edrophonium. Therefore, we recommend the use of neostigmine for routine paediatric practice.

Pharmacodynamic effects of 51W89, an isomer of atracurium, in children during halothane anaesthesia.

51W89 is one of the 10 stereoisomers of atracurium with less propensity to release histamine than atracurium. We evaluated dose-response data and neuromuscular effects of 2 x ED95 dose and maintenance doses of 51W89 during halothane anaesthesia in 68 children, 2-12 yr old. Neuromuscular function was monitored by evoked adductor pollicis EMG. Log-probit, single-dose, dose-response data gave ED50 and ED95 values of 23 and 41 micrograms kg-1, respectively, for 51W89. Twice the ED95 dose (80 micrograms kg-1) had an onset time (time from administration to maximum effect) of 2.5 (SD 0.8) min, a clinical duration (time to 25% EMG recovery) of 31 (7) min and a recovery index (time from 25 to 75% EMG recovery) of 11.1 (1.7) min. Seventy-nine incremental doses of 51W89 of 94 (19) micrograms kg-1. Duration of effect of incremental doses remained constant within individuals reflecting non-cumulative properties. There were insignificant changes in arterial pressure and heart rate after 51W89 and no side effects were observed. We regard 51W89 as a promising, non-cumulative, intermediate-acting neuromuscular blocking agent the effects of which can be antagonized easily by neostigmine.

Synergism between atracurium and vecuronium in infants and children during nitrous oxide-oxygen-alfentanil anaesthesia.

This study was undertaken to see if infants are more sensitive than children to a combination of atracurium and vecuronium in an equipotent dose ratio: (microgram: microgram) 5:1 in infants and 4:1 in children. We studied 15 infants (1-11 months old) and 15 children (3-10 yr old) during nitrous oxide-oxygen-alfentanil anaesthesia. Neuromuscular function was recorded by adductor pollicis EMG. An individual dose-response curve of the atracurium-vecuronium combination was determined for every patient and its potency compared with that of the parent agents alone. The combination was significantly more potent than one parent agent, both in infants (P < 0.01) and in children (P < 0.0001). However, infants were less sensitive than children to synergism produced by the atracurium-vecuronium combination: if the ED50 dose of the parent agent is defined as one dose equivalent, then the mean ED50 doses of the combination were 0.81 (SEM 0.05) and 0.64 (0.03) dose equivalents in infants and children, respectively (P < 0.01). We suggest that an interaction between two binding sites of competitive neuromuscular blocking agents in postsynaptic acetylcholine receptors may explain both the synergism and sensitivity of infants to non-depolarizing neuromuscular blocking agents.

Pharmacodynamics of mivacurium in infants.

A computerized infusion system was used to determine mivacurium infusion requirements to maintain 95% and 50% neuromuscular block in 15 infants less than 1 yr of age. Neuromuscular block was measured by adductor pollicis EMG and anaesthesia maintained with 66% nitrous oxide in oxygen and alfentanil 50-100 micrograms kg-1 h-1. Neuromuscular block was produced by repeated bolus doses of mivacurium 0.1 mg kg-1; subsequently the target neuromuscular block was maintained by a closed loop infusion. Dose potency of mivacurium was similar to that previously published in children with a similar anaesthetic technique. Mean mivacurium requirement for 95% neuromuscular block was 820 (SD 300) micrograms kg-1 h-1, which represented an hourly requirement of 6.6 (1.5) individual ED95 doses. Infusion requirement for 50% neuromuscular block was 320 (150) micrograms kg-1 h-1. These infusion rates were similar to those in children. No side effects of mivacurium were noticed.

Frequency of train-of-four stimulation influences neuromuscular response.

We have compared the effects of two different frequencies of train-of-four stimulation of the ulnar nerve (2-Hz stimulation once every 10 or 20 s) on onset time and potency of atracurium, vecuronium and mivacurium during balanced anaesthesia. The adductor pollicis EMG was recorded simultaneously in both hands of 24 children aged 2-12 yr. After administration of an ED50 dose of each blocker, onset times were mean 21 (SEM 10) s shorter (P < 0.05) and decreases in neuromuscular function were 22 (3)% greater (P < 0.001) in the hand which was stimulated once every 10 s. We conclude that it is not possible to compare potency estimates of neuromuscular blocking agents if different stimulation patterns have been used.

Accelerated onset and delayed recovery of neuromuscular block induced by mivacurium preceded by pancuronium in children.

The goal of this study was to describe a technique which could shorten the time from mivacurium administration to peak neuromuscular block (NMB) after administration of the maximum recommended dose of mivacurium. Forty-eight pediatric patients were randomized into three groups and studied during nitrous oxide-alfentanil-thiopental anesthesia. Every patient received two blinded injections 3 min apart: either 15 micrograms/kg of pancuronium in 1 mL of saline followed by 170 or 200 micrograms/kg of mivacurium or saline followed by 200 micrograms/kg of mivacurium. Intravenous induction of anesthesia followed the first injection. Thenar electromyogram response to supramaximum train-of-four stimulation of the ulnar nerve at 10-s intervals was used for neuromuscular monitoring. Pretreatment with pancuronium significantly shortened the time to NMB and prolonged spontaneous recovery from NMB in comparison to the temporal course of NMB after administration of 200 micrograms/kg of mivacurium. Time from injection to 90% NMB averaged 116 (SEM 11) s after administration of 200 micrograms/kg of mivacurium, and 71 (7) s and 94 (11) s when 200 micrograms/kg or 170 micrograms/kg of mivacurium, respectively, was preceded by pancuronium (P = 0.0095). Mean times from injection to recovery of neuromuscular function to > 25% of baseline (T25) and to train-of-four ratio of 0.75 were 9.1 (0.7) and 15.8 (1.2) min, respectively, after administration of 200 micrograms/kg of mivacurium alone. T25 and train-of-four of 0.75 occurred significantly later at 21.9 (1.8) and 35.0 (2.8) min, respectively (P = 0.0001), when 200 micrograms/kg of mivacurium was preceded by 15 micrograms/kg of pancuronium.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of thumb acceleration and thenar EMG in a pharmacodynamic study of alcuronium.

We compared thumb acceleration (Acc) and thenar electromyography (EMG) techniques by evaluating the neuromuscular blocking properties of alcuronium in 14 ASA physical status I patients. The dose-response curves determined by the two techniques were parallel but the EMG-curve was shifted 25% to the right (P less than 0.001). Acc reflected 8-11% greater neuromuscular block than simultaneous EMG in every patients (P less than 0.05). Concurrently, the duration of greater than 90% neuromuscular block maintained by alcuronium 280 micrograms/kg was significantly longer when measured by the Acc transducer (30 vs. 19 min, P less than 0.001). Although the TOF ratios were in good correlation (r2 = 0.82), clinically significant differences existed between the two simultaneous techniques. The results underline the importance of the method of assessment of neuromuscular transmission when evaluating the action of neuromuscular blocking drugs.

Two-dose technique to create an individual dose-response curve for atracurium.

While monitoring the thenar EMG response to ulnar nerve stimulation, the authors gave either 105, 150, 210, or 300 micrograms/kg of atracurium to 60 patients. The maximal neuromuscular responses were plotted on a log-probit paper. The individual second dose required to produce 95% neuromuscular block (NMB) was estimated from a graph drawn on the paper. The maximal response following this second dose was then plotted. The mean maximal response following the second atracurium dose was 95.5% (SD range, 92.6-97.4%) NMB. The two dose-response points thus acquired resulted in the individual two-dose dose-response curve. The ED50 and ED95 and slope of the two-dose dose-response curve were compared with the single-dose dose-response curve. The average ED50 and ED95 determined by the two-dose and the single-dose techniques were nearly identical [160 micrograms/kg (SD range, 126-201 micrograms/kg) vs. 164 micrograms/kg (SD range, 150-179 micrograms/kg) and 302 micrograms/kg (SD range, 251-363 micrograms/kg) vs. 336 micrograms/kg (SD range, 274-411 micrograms/kg) respectively]. Also, the slopes of the curves were similar [6.2 (SD range, 5.2-7.2) vs. 5.4 (SD range, 4.5-6.4) probit/log]. It is therefore possible to construct an individual dose-response curve for atracurium within 7-9 min and to determine individual pharmacodynamic characteristics of atracurium from this curve.

Assessment of anaesthetic adequacy with upper facial and abdominal wall EMG.

We compared changes in biopotentials arising from upper facial (FEMG) and abdominal (AEMG) muscles associated with alterations in alveolar enflurane concentration and neuromuscular block. Induction of anaesthesia significantly reduced both FEMG and AEMG mean amplitudes (-60% and -43%, respectively). Neuromuscular blocker-induced abolition of the electrically evoked thenar EMG response did not prevent FEMG and/or AEMG activation during endotracheal intubation. Decreasing the alveolar enflurane concentration was associated with an increase in FEMG amplitude prior to visible signs of arousal in half of the patients. Movement and other signs of inadequate anaesthesia were associated with distinct increases in FEMG amplitude in 29 out of 30 patients. Recovery from neuromuscular block during unchanged alveolar enflurane concentration was associated with increasing amplitudes of both FEMG and AEMG. Finally, very low-amplitude FEMG recordings were always associated with relaxed abdominal muscles.