Regional cerebral blood flow in weight-restored anorexia nervosa: a preliminary study.

Twenty-one individuals (19 females, two males) with teenage-onset anorexia nervosa (AN), 19 of whom were weight restored, were assessed using single-photon emission computed tomography (SPECT) 7 years after onset of AN, at a mean age of 22 years. For comparison we recruited a younger group without neuropsychiatric disorder (mean age 9:8 years; five females, four males) who underwent SPECT at follow-up after an operation for coarctation of the aorta or because of lymphatic leukaemia. Ethical considerations precluded the study of regional cerebral blood flow (rCBF) in participants with completely normal development. The group with AN showed marked hypoperfusion of temporal, parietal, occipital, and orbitofrontal lobes compared to the contrast group. rCBF was not correlated to body mass index in any of the groups. Results suggest that, even long after re-feeding has occurred, AN may be associated with moderate to severe cerebral blood flow hypoperfusion in the temporoparietal (or temporoparietooccipital) region and in the orbitofrontal region. A limitation of the study is that the young contrast group in this study could be expected to have a higher global rCBF than the group with AN. However, this should not significantly affect the relative values used in this study.

Regional cerebral blood flow and neuron-specific enolase in cerebrospinal fluid in children with acute lymphoblastic leukemia during induction treatment.

PURPOSE: To investigate possible side effects on the central nervous system from intrathecal methotrexate given during induction treatment for acute lymphoblastic leukemia in childhood. PATIENTS AND METHODS: Twenty-five children with acute lymphoblastic leukemia were examined by cerebral single photon emission computed tomography at the beginning of treatment (16 untreated, 9 during the first week) and after 4 weeks of treatment. Cerebrospinal fluid was sampled for analyses of neuron-specific enolase on four occasions in 54 patients. RESULTS: Regional cerebral blood flow became impaired during treatment in all patients. The single photon emission computed tomography score for nonhomogeneous perfusion increased from 6.4/50 to 16.6/50. Hypoperfusion was global without any clear preference for any lobe. The cerebellum was not affected. Neuron-specific enolase increased significantly during treatment, with a peak after 1 week, followed by a gradual decrease, but it was still significantly elevated after 4 weeks. CONCLUSIONS: Nonhomogeneous cerebral hypoperfusion was found in all patients during induction treatment, including repeated intrathecal administration of methotrexate, but before systemic high-dose methotrexate. Signs of neuronal injury, in the form of a moderate increase in neuron-specific enolase in the cerebrospinal fluid, were found early in the treatment. Follow-up is needed to evaluate the long-term impact of these findings.

Computed tomography and single-photon emission computed tomography as diagnostic tools in acquired brain injury among children and adolescents.

Twenty children with acquired brain injuries were investigated with CT and SPECT. The findings were related to the clinical outcome judged at discharge following acute care after the injury and at follow-up 5 years later. The abnormalities that were found were classified for each lobe on a scale ranging from 0 (normal) to 5 (severe abnormality). The patients were divided into two groups showing mild and severe injury. CT and SPECT revealed similar results in the patients with severe injury, but in the group of mildly injured children the number of affected lobes and scores indicated by SPECT were significantly higher than those indicated by CT. SPECT also differentiated more effectively between the two outcome groups. This supports the hypothesis that SPECT could be used as an instrument to objectivise minor sequelae and that SPECT and CT are both useful methods for forecasting outcome.

Studies of cerebral blood flow in children with acute lymphoblastic leukemia: case reports of six children treated with methotrexate examined by single photon emission computed tomography.

PURPOSE: Cranial irradiation has been widely used in order to prevent central nervous system (CNS) relapse of acute lymphoblastic leukemia (ALL) in childhood. Owing to the risk of late side effects, the Nordic Society for Pediatric Hematology and Oncology (NOPHO) replaced CNS irradiation with systemic high-dose methotrexate (HDMTX) in 1992. A prospective study of the effects of HDMTX and intrathecal MTX on CNS function is in progress at our center. PATIENTS AND METHODS: Six ALL patients underwent (99m)Tc-HMPAO single-photon emission computed tomography (SPECT) examination of regional cerebral blood flow (rCBF): three owing to neurological symptoms during treatment for ALL and the other three as part of the study. RESULTS: All the patients had various degrees of disturbed rCBF, which was more pronounced in the patients with neurological symptoms. One patient had severe symptoms and impaired rCBF after three intrathecal injections of MTX but before administration of HDMTX. CONCLUSIONS: Impaired cerebral perfusion was found in patients with and without neurological symptoms during treatment for ALL. The impact of these findings is still unknown, from both the long- and the short-term perspective. The possibility that intrathecal MTX alone or in combination with HDMTX may affect rCBF through vascular damage should be further investigated, in terms of both mechanisms and clinical significance.

Regional cerebral blood flow abnormalities in Rett syndrome.

Sixteen Rett syndrome (RS) girls and 1 24 year old RS woman were compared with 16 neurologically healthy children as to the regional cerebral blood flow (rCBF). Hypoperfusion of the frontal lobes and parts of the midbrain was found in RS, with significant differences to controls at latest by the age of three to four years. The findings were in accordance with previous reports of morphological, neuroradiological and functional abnormalities in these areas, compatible with a statement that structures in the midbrain and in the frontal lobes may have particular pathophysiological relevance in RS.

Radiopharmaceutical dosage of 99Tcm-HMPAO for cerebral blood flow SPET studies in children.

Four methods of calculating the activity of 99Tcm-hexamethylpropyleneamine oxime to be administered in cerebral blood flow investigations of children were evaluated in patient studies. Three of the methods were based on the size of the child. We also constructed a theoretical dosage model based on physiological data and attenuation effects. The aim of the study was to find a dosage calculation method that gave the same image quality for children of all ages as well as for adults. The results showed that the dosage method based on body weight is the only one of the four methods that does not exhibit an age-dependent variation in image quality and therefore this method is recommended.

Influence of breathing pattern on transcutaneous oxygen and carbon dioxide tension during histamine provocation in children with bronchial asthma.

The influence of the breathing pattern on transcutaneous blood gases was evaluated in 18 boys and 8 girls 7-18 years of age, with bronchial asthma, during bronchial provocation with histamine-HCl. Transcutaneous oxygen tension (tcPO2), carbon dioxide tension (tcPCO2) and the breathing pattern assessed by the transthoracic impedance technique were continuously monitored during the provocation. At reaction, when the fall in the forced expiratory volume in 1 s (FEV1) was 20% or more, the tcPO2 fell by 15% or more below the baseline in 22/26 and by 20% or more in 14/26 children. In some children, a marked fall in the tcPO2 was already noted after the saline inhalation and the first histamine dose steps without simultaneous changes in the FEV1. This early fall in the tcPO2 correlated to changes in the breathing pattern and was interpreted as a sign of compensatory hypoventilation secondary to the hyperventilation observed during the inhalations. We conclude that transcutaneous oxygen tension can be used as an indicator of a bronchial reaction during bronchial provocation tests in children only if one takes account of the fact that the breathing pattern during the inhalation of the challenge compound per se has an effect on the oxygen tension.

Respiratory resistance and transcutaneous PO2 during histamine provocation in children with bronchial asthma.

Bronchial reactivity was assessed in 66 children with bronchial asthma (aged 8-15 years) by provocation with histamine-HCl during a symptom-free period. A significant bronchial reaction to histamine was defined as a 50% increase in the resistance of the respiratory system (Rrs) determined by the forced oscillation technique. The provocative dose causing a 50% increase in the Rrs (PD50Rrs) was interpolated from the log dose-response curve. The mean PD50Rrs was significantly lower in children with asthma (0.22 mg/mL) compared with a group of healthy children in the same age range (1.55 mg/mL) (P < 0.001). In children with clinically severe asthma, the mean PD50Rrs was lower (0.13 mg/mL) than in children with mild asthma (0.34 mg/mL) (P < 0.001). Transcutaneous PO2 (PtcO2) was monitored in 25 of the children with asthma. In this group the proportion of mild and severe asthma, the baseline lung function variables, and the PD50Rrs were not significantly different from those of the whole group of children. During the reaction, the PtcO2 fell on average by 29% of the baseline value (P < 0.001); in 88% of the children, the fall in PtcO2 was 20% or more of the baseline value. We conclude that histamine provocation tests using the forced oscillation technique and transcutaneous PO2 to assess a bronchial reaction have a good discriminatory capacity for different degrees of clinical severity of asthma in children.

SPECT (Single Photon Emission Computed Tomography) in 31 children and adolescents with autism and autistic-like conditions.

SPECT with Tc-99m-HM-PAO was used in examining 31 patients with autism and autistic-like conditions. Sixteen of these had autistic disorder/autistic-like conditions with associated epilepsy. The autistic disorder group without epilepsy was relatively high functioning. All 31 patients showed reduction of regional cerebral blood flow in the temporal lobes. There was no clear difference between the groups with and without epilepsy, suggesting that seizure disorder per se could not account for the findings.

Transcutaneous blood gas monitoring during salbutamol inhalations in young children with acute asthmatic symptoms.

The effect of salbutamol inhalations on transcutaneous blood gases was investigated in 23 children (aged 11 months-2.5 years) with asthmatic symptoms. After one salbutamol inhalation there was a mean increase in transcutaneous PO2 (tcPO2) of 0.5 kPa (P less than 0.01); after a second dose given 30 minutes later, the mean increase was 1.2 kPa (P less than 0.001). The increase in tcPO2 after only one dose of salbutamol was significantly correlated to age (P less than 0.01). No such correlation was observed after a second dose. The overall increase in tcPO2 after two salbutamol inhalations showed a negative correlation to the duration of the current symptomatic period (P less than 0.05). We conclude that salbutamol inhalations have beneficial effects in young children with acute asthmatic symptoms, even below the age of 18 months, provided that an adequate dose reaches the lung and preferably at an early stage of obstruction.

Pronounced detrusor hypercontractility in infants with gross bilateral reflux.

In this study the prevalence of bladder dysfunction in 18 children with gross bilateral reflux was investigated via cystometric recordings. In all except 1 infant maximal voiding detrusor pressure was 100 cm. or greater water (range 86 to 244). Pronounced instability during filling (overt instability) with pressure waves above baseline (mean 65 cm. water, range 42 to 194) was found in 9 infants. Another 5 children had evidence to suggest an uninhibited bladder, not manifested as unstable contractions during filling but as covert instability, meaning that the first unstable contraction was transformed into a premature and forceful voiding contraction. The high detrusor pressures found in 18 children with gross bilateral reflux during the voiding phase but also during the filling phase in half of the children suggest that a hypercontractile detrusor may be a contributory factor for the development of reflux even in this age group.

Evaluation of cerebrospinal fluid shunt function in hydrocephalic children using 99mTc-DTPA.

The increasing numbers and survival of children with shunt-treated hydrocephalus make it mandatory to refine the methods for cerebrospinal fluid (CSF) shunt function evaluation. Radionuclide shuntography with 99mTc-DTPA, which has proved to be a safe and effective method, was performed in eight children with suspected CSF-shunt dysfunction. Characteristic shuntography patterns were found for proximal and distal CSF-shunt catheter obstruction as well as for overdrainage and normal CSF-shunt function. Shuntography contributed to the explanation of suspected CSF-shunt dysfunction in all children investigated.

Psychological and respiratory physiological effects of a physical exercise programme on boys with severe asthma.

Ten boys 9-12 years of age with severe perennial asthma participated in a physical exercise programme lasting 8 months. Pulmonary function and psychological tests were performed before training, immediately after, and one year after the end of the exercise programme. Static lung volumes, flow-volume variables and histamine tolerance were used as indicators of pulmonary function. Ego structure, body image, social development and concentration capacity were used as indicators of personality development. Before the study, the group had high FRC (p less than 0.05) and RV (p less than 0.001), low FEV1, MEF50 and MEF25 (all p less than 0.001) and low histamine tolerance. They showed marked disturbances in their personality development with low scores in psychological variables. During the training period, MEF50 and MEF25 increased slightly (p less than 0.01). Marked improvement was observed in all psychological variables (p less than 0.001). The positive effects remained during the following year. The marked and lasting improvement in personality development was regarded as an essential factor behind the more modest positive clinical and pulmonary function changes. The results emphasize the importance of including exercise programmes in the treatment of children with asthma.

Brain single photon emission computed tomography (SPECT) in neuropediatrics.

The clinical value in neuropediatrics of [99mTc]HM-PAO brain single photon emission computed tomography was preliminary evaluated by the consecutive investigation of 79 children. Planned epilepsy surgery was the most common indication for the investigation. In 56 children investigated because of epilepsy, SPECT yielded relevant information in 79% of cases examined. The corresponding figures for magnetic resonance imaging and CT were 49% of 35 and 36% of 56 cases, respectively. All 22 children with an epileptic focus, ascertained by freedom from seizures after removal of the area or by consistent neurophysiological and neuroradiological findings, also had abnormal perfusion in the relevant area. Twenty-three children were examined because of neurological signs and symptoms other than epilepsy. SPECT findings were useful for elucidating neonatal brain impairments. Hypoperfused areas in the brain of asphyxiated infants and in posthemorrhagic hydrocephalus corresponded to neuroradiological and autopsy findings. SPECT was found to be an excellent tool when analysing cerebrovascular accidents. In cases with signs and symptoms of a diffuse severe encephalopathy, SPECT did not clarify the etiology but provided information on the distribution of the lesions and probable underlying pathophysiological mechanisms.

Respiratory sequelae and lung function after whooping cough in infancy.

The lung function of 31 children, aged 6-13 years, who had whooping cough as infants and 32 control children matched for age, sex, and residence area were compared in a community based cohort study. Family history of obstructive airway disease, smoking habits in the family, atopy, and other background factors examined were similar in the two groups. The ratios of recalled repeated acute respiratory infections did not differ among the groups. Children in the control group were slightly more involved in physical activities. History of obstructive airway disease, findings on chest radiography, and distribution of immunoglobulin concentrations, including IgE, did not differ significantly. Lung function before and after exercise and after inhalation of salbutamol were not different. No impairment of small airways was detected. Our data do not support the hypothesis that whooping cough in itself is a causal factor for later obstructive respiratory disease.

Untreated bacteriuria in asymptomatic girls with renal scarring.

Recurrences of bacteriuria after treatment occur in 50% to 80% of asymptomatic patients. Previous experience with short-term treatment as well as long-term prophylaxis has been disappointing, with a significant risk of infections, ie, development of symptoms after treatment. Results with nontreatment are described in this report with reference to clinical course, renal growth, and glomerular filtration rate in 26 asymptomatic girls with established renal scarring and bacteriuria. Acute pyelonephritis was not seen in those with continuing bacteriuria or spontaneous clearance. Neither in scarred nor in unscarred kidneys did the duration of bacteriuria influence renal growth or glomerular filtration rate. Asymptomatic patients with bacteriuria may gain from nontreatment and may have a reduced risk of pyelonephritic attacks.

Hypoxia reinforces laryngeal reflex bradycardia in infants.

The laryngeal chemoreflex involves bradycardia, apnea, swallowing and peripheral vasoconstriction. This reflex was studied in twelve infants, aged 5 days-28 weeks, who had sustained an apparent life-threatening event or were siblings of infants who had died of the sudden infant death syndrome. The bradycardic and apneic components of the reflex were found to be significantly, and sometimes powerfully, reinforced when elicited by pharyngeal water instillation during acute, mild hypoxia (transcutaneous PO2 4.6-8.3 kPa). Apnea duration during normoxia was 0.7-15 sec, and during hypoxia 2-30 sec. Heart rate change ranged from +26% to -21% during normoxia, as compared with -4% to -63% during hypoxia. The percentage change in heart rate was found to inversely correlate with the transcutaneous PO2-level prevailing when the reflex was elicited. The conclusion is that there is a significant reinforcement of the cardiorespiratory adjustments when the laryngeal reflex is activated during simultaneous excitation of the peripheral arterial chemoreceptors. One infant, showing a particularly strong increase of the cardiorespiratory response to laryngeal receptor stimulation during hypoxia, later died of sudden infant death syndrome.

The epidemiology of sudden infant death syndrome and attacks of lifelessness in Sweden.

Infants who died showing the syndrome of sudden infant death (SIDS) and infants who survived attacks of lifelessness (AL) were examined in a prospective epidemiological multicentre study over 24 months covering close to 40% of all births in Sweden. Seventy SIDS cases and 34 cases of AL were observed, giving an incidence for SIDS of 0.94/1000 and for AL of 0.46/1000. This SIDS incidence is higher than that observed during the seventies. The boy/girl ratio was 1.4:1 for SIDS and 1.6:1 for AL. The age distribution for AL resembled that for SIDS. Similarities were also seen with regard to place of occurrence. Sixty per cent of the SIDS cases occurred during the daytime/evening. Twenty-nine per cent of the infants with AL had more than one apneic spell during the three-day-period around the attack, indicating a period of respiratory instability, but only 12% had such spells later on. None of the infants who had had AL died from SIDS. The possible relationship between AL and SIDS is discussed.