Quantitative Magnetic Resonance Imaging of Human Brain Development: Ages 4-18

Brain magnetic resonance images (MRI) of 104 healthy childrenand adolescents, aged 4–18, showed significant effectsof age and gender on brain morphometry. Males had larger cerebral(9%) and cerebellar (8%) volumes (P < 0.0001 and P = 0.008.respectively), which remained significant even after correctionfor height and weight After adjusting for cerebral size, theputamen and globus pallidus remained larger in males, whilerelative caudate size was larger in females. Neither cerebralnor cerebellar volume changed significantly across this agerange. Lateral ventricular volume increased significantly inmales (trend for females), with males showing an increase inslope after age 11. In males only, caudate and putamen decreasedwith age (P = 0.007 and 0.05, respectively). The left lateralventricles and putamen were significantly greater than the rightP = 0.01 and 0.0001, respectively). In contrast, the cerebralhemispheres and caudate showed a highly consistent right greater-than-leftasymmetry (P < 0.0001 for both). All volumes demonstrateda high degree of variability. These findings highlight gender-specificmaturational changes of the developing brain and the need forlarge gender-matched samples in pediatric neuropsychiatric studies.     

A 2-year prospective follow-up study of children and adolescents with disruptive behavior disorders. Prediction by cerebrospinal fluid 5-hydroxyindoleacetic acid, homovanillic acid, and autonomic measures?

A 2-year prospective follow-up study of 100% (N = 29) of a sample of children and adolescents with disruptive behavior disorders found that the baseline lumbar cerebrospinal fluid monoamine metabolite concentration and autonomic nervous system activity predicted some subsequent outcomes. The 5-hydroxyindoleacetic acid concentration significantly predicted severity of physical aggression during follow-up. The skin conductance level significantly predicted institutionalization. Correlations were in predicted directions with lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and autonomic activity correlated with poor outcome. Moreover, in multivariate analyses, which included nonlaboratory measures as predictors, cerebrospinal fluid and autonomic measures still contributed significantly to the prediction. However, hypothesized predictions of cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations for suicide attempts and of low autonomic nervous system activity for arrests were not supported thus far. Patients are still at risk; consequently, these results must be considered preliminary. Nonetheless, the results suggest that further investigation of relationships between biological factors and outcome of children with disruptive behavior disorders is warranted.     

The effect of methylphenidate on urinary catecholamine excretion in hyperactivity: a partial replication

Children with attention deficit disorder with hyperactivity were treated with methylphenidate HCl (0.74 +/- 0.2 mg/kg/day) for 2 weeks in an open trial to assess changes in the urinary excretion of catecholamines and behavior. The purpose of this study was to confirm earlier work that methylphenidate has a distinctly different effect on urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion as compared to earlier studies with dextroamphetamine. Results confirmed the earlier finding that methylphenidate does not significantly change urinary MHPG excretion. No significant relationship was found between behavioral change and any of the urinary catecholamines or metabolites measured.     

Concentration gradient of CSF monoamine metabolites in children and adolescents

Whether the lumbar cerebrospinal fluid (CSF) concentration gradient of monoamine metabolites found in adults is influenced by age or pubertal status was studied in 26 children ranging from 6.5 to 17.3 years of age. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were assayed by high-power liquid chromatography (HPLC) with electrochemical detection. Eight patients were prepubertal (Tanner stage I). The slopes in units of picomoles/milliliter/milliliter for regression lines for CSF monoamine metabolite concentrations versus milliliter of CSF collected were 5.07 +/- 0.65, 10.13 +/- 2.0, and 0.67 +/- 0.22 for 5-HIAA, HVA, and MHPG, respectively, for the group as a whole. Significant correlations with age, height, weight, or Tanner stage were not found for the HVA or MHPG concentration gradients. Tanner stage and 5-HIAA slope were significantly correlated. Three of eight prepubertal patients had nonsignificant 5-HIAA gradients. CSF studies in pediatric populations must control for aliquot collected, as the size of the gradient could produce differences sufficient to mimic a "positive" clinical study if the aliquots collected are not the same.     

Functional proteomics mapping of a human signaling pathway

Access to the human genome facilitates extensive functional proteomics studies. Here, we present an integrated approach combining large-scale protein interaction mapping, exploration of the interaction network, and cellular functional assays performed on newly identified proteins involved in a human signaling pathway. As a proof of principle, we studied the Smad signaling system, which is regulated by members of the transforming growth factor beta (TGFbeta) superfamily. We used two-hybrid screening to map Smad signaling protein-protein interactions and to establish a network of 755 interactions, involving 591 proteins, 179 of which were poorly or not annotated. The exploration of such complex interaction databases is improved by the use of PIMRider, a dedicated navigation tool accessible through the Web. The biological meaning of this network is illustrated by the presence of 18 known Smad-associated proteins. Functional assays performed in mammalian cells including siRNA knock-down experiments identified eight novel proteins involved in Smad signaling, thus validating this integrated functional proteomics approach.     

The diagnosis of malignant follicular neoplasms of the thyroid by needle biopsy

To test the value of needle biopsy for a diagnosis of follicular thyroid malignancy, we compared needle biopsy and surgical diagnoses for 1005 patients. There were 67 follicular carcinomas, 34 Hurthle cell carcinomas, and 39 follicular variants of papillary carcinoma. Malignancy was diagnosed or suspected by biopsy for 114 of the cancers (82%), considered "possible" for 24 (17%), and misdiagnosed as "benign" in 2. Sensitivity of fine-needle biopsy (FNB) for the diagnosis of 39 cancers approximated that of large-needle biopsy (LNB) for 101 cancers 2 cm or larger. Diagnostic specificity for cancer varied with the degree of cytologic or histologic abnormality. Specificity of FNB was comparable to LNB on nodules large enough for both procedures. Specificity of FNB on nodules too small for LNB was substantially less. The sensitivity of needle biopsy allows selection of many follicular nodules for observation. Knowledge of the probability of cancer for each cytologic or histologic diagnosis is useful in determination of the need for thyroid surgery.     

The treatment of spondylotic cervical myelopathy by ventral discectomy. Long term results on 121 patients

The pathophysiology of spondylotic cervical myeolopathy is still a matter of discussion. This paper presents a series of 126 patients operated on using a ventral approach. In 47% of the patients only a spondylotic narrowing of the spinal canal was present and in 35% an additional disc herniation was found. In 13% of the cases however a soft disc without spondylotic spures was found and in 5% a dislocation of vertebral bodies. We found a marked male preponderance of 77%, mean age was 51.6 years, ranging from 25–50 years. Most patients were operated on at the levels of C4/5 and C5/6. Observation time covered a period of 3–10 years. The outcome was rated relatively to the preoperative degree of disablement using a questionnaire for the patients and their family doctors. We found a marked difference in the answers, especially in rating deterioration, which was stated by patients in 34%, by physicians only in 12%. Another finding was the time-related out-come. We found best results with 75% improvement and 5% deterioration between 3–6 months postoperatively, with increasing time the results decreased to 33% improvement, 33% identical statys and in 33% a deterioration related to the preoperative status must be noted.     

Cavernous Haemangiomas of the Spinal Cord. A Review of 117 Cases

 The data of 48 studies (published between 1903 and 1996), presenting information of all together 107 patients (108 lesions) regarding pre-treatment clinical and radiological factors, treatment strategies, and the outcome, plus our own experience of nine patients were retrospectively re-analyzed. The prognostic influence of pre-treatment factors was estimated with the chi-square statistics. Clinical evaluation before/after treatment was performed using the Frankel scale. The average bleeding rate was obtained from the ratio of percentage of first bleeding events in the population to the mean age of the population.  There were 47 males and 69 females (aged from twelve to 88 years). Thirty nine percent of the lesions were found in the cervical, 54% in the thoracic (30% upper, 24% lower) and 7% in the lumbar cord. The peak age of presentation was in the fourth decade, the median duration of symptoms was 32 months. Clinical symptoms before treatment were progressive in all cases. Three patterns of clinical presentation could be identified: a) episodes of stepwise clinical deterioration (30%), b) slow progression of neurological decline (41%), c) acute onset with rapid or gradual decline over weeks or months (26%). 58% of the lesions showed clinical or radiological signs of haemorrhage. In 66% of surgical patients (91 efficiently documented cases), clinical improvement was achieved, 28% remained unchanged and 6% deteriorated. Whereas age, sex and lesion location had no influence on the results, duration of symptoms (<three years) correlated significantly to a better outcome (p<0.02).  Surgical management in symptomatic patients is recommended. Once clinical signs caused by the malformation have appeared, the patients tend to experience progressive neurological deterioration.