Disabilities and cognition in children and adolescents with 22q11 deletion syndrome.

The purpose of this study was to investigate cognitive and other disabilities in children and adolescents with 22q11 deletion syndrome. Thirty-three children (15 females, 18 males; age range 3 to 19y, median 7y 6mo) with 22q11 deletion were investigated for growth, development, neurology, cognition, motor function, and participation (measured as handicap**). Half of the children had never crawled, although they had shuffled, and commencement of walking was delayed (mean 18mo, SD 6mo). Hypotonia was found in 25 and poor balance in 24 of the 33 children; 17 out of 27 had definite motor problems, including two with spastic hemiplegia. Intelligence quotient (IQ) range was 50 to 100. Eleven patients had an IQ below 70, and 15 between 70 and 84. Verbal IQ was higher than Performance IQ. Level of handicap within the study group was considered moderate, and all but one child had extra support at school. We conclude that children with 22q11 deletion syndrome have multiple neurological, motor, and cognitive problems. Although the severity and number of problems varies, the combination of impairments and disabilities results in a low level of participation.

Systemic adenosine infusion reduces the area of tactile allodynia in neuropathic pain following peripheral nerve injury: a multi-centre, placebo-controlled study.

Systemic adenosine has been shown in earlier case reports and a small placebo-controlled study to reduce pathological sensory dysfunction such as tactile allodynia in neuropathic pain. To evaluate this further, the effects of systemic adenosine infusion (50 microg/kg/min for 60 min) on tactile sensory dysfunction and pain was evaluated in 26 patients suffering peripheral neuropathic pain characterized by dynamic tactile allodynia. A randomized, cross-over, double-blind, placebo-controlled technique was used in this multi-centre study. Psychophysical methods were used to evaluate sensory dysfunction and spontaneous pain. The area of dynamic tactile allodynia was significantly reduced by adenosine compared with placebo (p=0.043), but spontaneous pain and tactile pain threshold were not significantly improved compared with the effects of placebo treatment. As a secondary outcome, a higher incidence of positive subjective effects on the clinical pain condition, in a few cases with long duration (several months), following adenosine treatment was found when the global effect of respective treatment was assessed (p=0.028). The results demonstrate involvement of adenosine receptor-sensitive pain mechanisms in some aspects of the sensory dysfunction often found in neuropathic pain.

[CATCH22 or 22q11 deletion syndrome. An underdiagnosed and misunderstood disease category with a variable clinical picture]. / CATCH 22-syndrom/22q11-deletionssyndrom. Underdiagnostiserad och missförstådd sjukdomsgrupp med skiftande klinisk bild.

Patients with CATCH 22 or 22q11 deletion syndrome constitute a fast growing category in Sweden as it is still underdiagnosed. In a series of 54 patients the predominant features were found to be speech and language difficulties, cardiac malformations, susceptibility to infection, learning and behavioural problems, hypoparathyroidism, minor motor deficits, and characteristic facies. The severity of these problems varied individually, but as the patients had numerous symptoms and disabilities the overall degree of handicap was considerable. Thus, regular evaluation of the patient's condition and overall need of care is important.

The safety and efficacy of intrathecal adenosine in patients with chronic neuropathic pain.

UNLABELLED: Adenosine and adenosine analogs decrease pain-like behavior in animal models of both acute nociceptive and neuropathic pain via adenosine receptor activation at spinal and/or supraspinal levels. This open study is the first in a series of intrathecal (IT) adenosine administration studied for the evaluation of efficacy and side effects in 14 patients. All had chronic neuropathic pain with tactile hyperalgesia and/or allodynia primarily of traumatic origin. The effects of IT adenosine (500 microg [n = 9] or 1000 microg [n = 5]) were evaluated. Approximate areas of tactile pain were mapped. Spontaneous and evoked pain (visual analog scale score 0-100) and tactile pain thresholds were assessed before and 60 min after injection. The injection caused transient pain (<60 min) in the lumbar region in five patients. There were no other side effects. Spontaneous and evoked pain was reduced (median score from 65 to 24 [P<0.01] and from 71 to 12 [P<0.01], respectively) in parallel with increased tactile pain thresholds in allodynic areas. Areas of tactile hyperalgesia/allodynia were reduced (median reduction 90%; P<0.001). Twelve patients experienced pain relief (median 24 h). We conclude that IT adenosine transiently causes lumbar pain in a subgroup of patients and may reduce various aspects of chronic neuropathic pain. IMPLICATIONS: This is the first series of patients with chronic neuropathic pain in which tolerability to spinal adenosine administration has been evaluated. A subset of patients reported transient low back pain as the only side effect. Spontaneous and evoked pain intensity decreased in most patients, an effect lasting for a median of 24 h.

Systemic adenosine infusion alleviates spontaneous and stimulus evoked pain in patients with peripheral neuropathic pain.

In seven patients with peripheral neuropathic pain, the effect of systemic adenosine infusion on pain symptoms was evaluated in a double-blind, placebo controlled, cross-over study. The study infusions, adenosine (50 micrograms.kg-1.min-1) or placebo, were given intravenously (IV) during 45-60 min at two separate occasions. Before and during infusions, bedside examination of sensibility and quantitative sensory testing (QST), i.e., assessments of perception thresholds for touch, touch-evoked pain, cold, warmth, painful heat, and cold, were performed. In the neuropathic area, sensation magnitude was rated by a visual analog scale (100 mm VAS) using a pin and at perception threshold for touch-evoked pain using von Frey filaments. Adenosine infusion reduced spontaneous pain (P < 0.05), and caused an increase of the touch-evoked pain threshold from 10.8 +/- 5.3 to 22.2 +/- 6.9 g (P < 0.05), whereas placebo had no effect. Pain intensity at perception threshold for touch-evoked pain was, however, unaltered. Pinprick-evoked pain in the neuropathic areas was reduced from 53 +/- 11 to 29 +/- 10 mm (P < 0.05). No other sensory modality was consistently changed during adenosine infusion. In conclusion, the present study demonstrates that adenosine infusion alleviates spontaneous neuropathic pain, tactile allodynia, and pinprick hyperalgesia in patients with peripheral neuropathic disorders, probably by a central mechanism of action.

Changes of neuropeptide concentrations in the brain following experimentally induced mononeuropathy in Wistar Kyoto and spontaneously hypertensive rats.

The effect of unilateral, experimentally induced, mononeuropathy on concentrations of neuropeptide Y (NPY), neurokinin A (NKA), substance P (SP), calcitonin gene-related peptide CGRP) and galanin- (GAL-) like immunoreactivities (-LI) was studied in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rat brains. Two weeks following ligation of the sciatic nerve, significantly higher concentrations of NPY-LI were found in the hippocampus, striatum and occipital cortex of both rat strains. CGRP-LI and GAL-LI were increased in the hippocampus of WKY rats. NKA-LI and SP-LI were decreased to different degrees in the pituitary of the WKY and SHR rats, indicating that the changes of the tachykinins, CGRP and GAL were selectively associated with the basal level of sympathetic tone. The increased concentrations of NPY-LI in the brain, not influenced by sympathetic tone, may be part of a general defense reaction in response to trauma.

Systemic adenosine attenuates touch evoked allodynia induced by mustard oil in humans.

The effect of adenosine on tactile allodynia (secondary hyperalgesia) was studied in 6 healthy volunteers, using a double-blind, placebo controlled, cross-over design. Tactile allodynia was induced by topical application of mustard oil on the skin of the volar aspect of the forearm. Adenosine (50 micrograms kg-1 min-1) or saline was given intravenously for 20 min before the mustard oil application and continued for another 50 min. The tactile allodynic areas for brush and von Frey filament stimulation were both significantly reduced by approximately 50% during adenosine infusion, compared with placebo. The threshold for eliciting allodynia with von Frey filaments was not influenced by adenosine. The study shows that adenosine can reduce the area of mustard oil induced tactile allodynia.

Glial fibrillary acidic protein in the cerebrospinal fluid of children with autism and other neuropsychiatric disorders.

The cerebrospinal fluid (CSF) of 47 children and adolescents with autism was analyzed for the contents of two astroglial proteins, the glial fibrillary acidic protein (GFA) and S 100. The results were contrasted with those obtained in similarly aged cases with other neuropsychiatric disorders (n = 25) and in normal children (n = 10). S-100 did not discriminate the groups from each other. However, GFA in autism and autistic-like conditions was at a level almost three times that in the normal group. The results could implicate gliosis and unspecific brain damage in autism. An alternative model would be increased synapse turnover regardless of underlying cause.

A sensitive ELISA for glial fibrillary acidic protein: application in CSF of children.

In the present study we describe a sensitive ELISA for determination of glial fibrillary acidic protein (GFAP). To validate the method combined determinations of GFAP and S-100 protein were performed in cerebrospinal fluid (CSF) of normal children and children with autism. The GFAP ELISA is of sandwich type and uses the biotin-avidin system. Sensitivity was 16 pg/ml. Between-day precision was 0.079 (coeff. of variance). S-100 protein concentrations were measured using a commercially available ELISA kit. Normal CSF from children and young adults were analysed. The CSF levels of GFAP in normal children were low (16-163 pg/ml). Both GFAP and S-100 protein concentrations correlated with age (P < 0.01 and P < 0.05, respectively), but the GFAP increment was more pronounced, probably reflecting the age-dependent expansion of the fibrillary astrocytes in the central nervous system (CNS). GFAP levels in children with infantile autism were higher than those in normal children of the same age range. S-100 protein concentrations were similar in both groups. High levels of GFAP in combination with normal S-100 protein concentrations in CSF indicates reactive astrogliosis in the CNS. In conclusion, the sensitive ELISA described makes it possible to measure low levels of GFAP present in the CSF of children. Combined assays of GFAP and S-100 protein can be used to discriminate between acute and chronic brain disorders in children.

Growth hormone improves muscle protein metabolism and whole body nitrogen economy in man during a hyponitrogenous diet.

Healthy male volunteers (n = 12) were given a normocaloric hyponitrogenous diet for a conditioning period of 7 days. Thereafter they were blindly randomized to receive daily injections of methionyl recombinant human growth hormone (met-hGH) 0.06 IU/kg or saline during a second week of hyponitrogenous nutrition. The met-hGH group showed a lower urinary urea excretion and a lower serum concentration of urea as compared with the control group. In skeletal muscle, the polyribosome concentration, indicative of muscle protein synthesis, as well as the concentrations of glutamine, alanine, aspartate, serine, and threonine, decreased in the control group, whereas no such changes were seen in the met-hGH-treated group. Since provision of met-hGH prevented protein catabolism in muscle and improved whole body nitrogen economy, investigations of the possible beneficial effects of met-hGH to prevent skeletal muscle vast after surgical trauma are advocated.