Purpose By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS.

No abstract

Although chemotherapy is the mainstay of treatment when indicated, multicenter collaborative studies involving oncologists and neuro-ophthalmologists, both retrospective and prospective, are still needed to establish evidence-based guidelines for the management of children with OPGs.

Summary 1.Many lizards use caudal autotomy as a defensive strategy. However, subsequent costs related to the alteration of locomotor abilities might decrease the fitness of individuals. In this paper, the movement patterns of spontaneously moving Psammodromus algirus lizards and their escape performance running at high speed were compared before and after tail loss. A control tailed group was also studied to assess the repeatability of locomotor patterns between trials. 2. Tail loss had a significant effect on spontaneous movement patterns. Tailless individuals moved at significantly slower speeds during bursts of locomotion, and distances moved within bursts were significantly reduced. The overall time spent pausing increased, and, as a result, overall speeds decreased to an even greater extent than burst speeds. However, mean durations of individual locomotor bursts and mean pause durations did not change significantly after tail loss. 3. Loss of the tail decreased mean stride length, although the positive relation between stride length and speed was retained. 4. Escape performance was also greatly affected; loss of the tail resulted in substantially reduced attained, maximal and overall escape speeds. These changes resulted in shorter escape distances (the time of the first pause after the initiation of the escape response) because the mean duration of escape responses did not change. 5. The relevance of these alterations for the ecology of this species, and how individuals may compensate for the costs of tail loss, favouring autotomy as an escape strategy, are discussed.

Research indicates that norepinephrine enhances the working memory functions of the prefrontal cortex (PFC) through actions at post-synaptic, alpha-2A adrenoceptors.The current study examined the effects of the alpha-2A adrenoreceptor agonist, guanfacine (0.7 mg/kg, i.m.), compared to saline on SPECT measures of regional cerebral blood flow (rCBF) Evidence from a variety of disciplines indicates that norepinephrine (NE) has a critical beneficial influence on the working memory functions of the prefrontal cortex (PFC) through its actions at post-synaptic, alpha-2A adrenergic receptors (reviewed in Arnsten et al. 1996). In monkeys, the ability to perform spatial working memory tasks has been closely linked to the dorsolateral PFC (dlPFC) surrounding the principal sulcus, especially the caudal two thirds of the principal sulcal region (Goldman and Rosvold 1970;Goldman-Rakic 1987).Alpha-2 adrenergic agonists such as clonidine, guanfacine, and medetomidine can improve spatial working memory performance in monkeys (Arnsten et al. 1988), rats (Carlson et al. 1992), and humans (Coull et al. 1995;Jakala et al. 1999), but have little effect or impair tasks dependent on posterior cortices or hippocampus (reviewed in Arnsten 1998). Dose response curves are con- N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 23 , NO . 3 Guanfacine Increases PFC Blood Flow in Monkeys 241 sistent with beneficial actions at post-synaptic alpha-2 receptors, as the drugs become more potent and more efficacious in animals and patients with NE depletion (Arnsten and Goldman-Rakic 1985;Cai et al. 1993;Franowicz and Arnsten 1999;McEntee and Mair 1990). However, very high doses of guanfacine have recently been found to significantly improve spatial working memory performance in normal adult monkeys as well . It is likely that the alpha-2A receptor subtype underlies guanfacine's beneficial effects on working memory function (Arnsten et al. 1988;Tanila et al. 1999), and guanfacine is currently the most selective alpha-2A agonist available (Uhlen and Wikberg 1991).Several findings suggest that alpha-2 agonists improve, while alpha-2 antagonists impair, working memory function through direct actions in the PFC. For example, infusion of the alpha-2 antagonist, yohimbine, into the monkey PFC produces a delay-related impairment in working memory, whereas alpha-1 and beta adrenergic antagonists are without effect (Li and Mei 1994). Similarly, electrophysiological studies show that iontophoretic application of yohimbine onto PFC neurons suppresses delay-related activity, the cellular measure of working memory Sawaguchi 1998). Conversely, iontophoretic or systemic administration of clonidine increases delay-related firing, and this enhancement is reversed by iontophoretic application of yohimbine . Similarly, infusion of the alpha-2 agonist medetomidine, into aged rat PFC improves spatial working memory performance (Tanila et al. 1996).Very few studies have taken advantage of imaging technologies to examine NE alpha-2 mechanisms in the cortex. Most human studies ha...

No abstract

Decreased GCL-IPL thickness (

IMPORTANCE Monitoring young children with optic pathway gliomas (OPGs) for visual deterioration can be difficult owing to age-related noncompliance. Optical coherence tomography (OCT) measures of retinal nerve fiber layer (RNFL) thickness have been proposed as a surrogate marker of vision but this technique is also limited by patient cooperation.OBJECTIVE To determine whether measures of circumpapillary RNFL thickness, acquired with handheld OCT (HH-OCT) during sedation, can differentiate between young children with and without vision loss from OPGs. DESIGN, SETTING, AND PARTICIPANTSThis cross-sectional analysis of a prospective observational study was conducted at a tertiary-care children's hospital. Children with an OPG (sporadic or secondary to neurofibromatosis type 1) who were cooperative for visual acuity testing, but required sedation to complete magnetic resonance imaging, underwent HH-OCT imaging of the circumpapillary RNFL while sedated. MAIN OUTCOMES AND MEASURESArea under the curve of the receiver operating characteristic, sensitivity, specificity, positive predictive value, and negative predictive value of the average and quadrant-specific RNFL thicknesses.RESULTS Thirty-three children (64 eyes) met inclusion criteria (median age, 4.8 years; range, 1.8-12.6 years). In children with vision loss (abnormal visual acuity and/or visual field), RNFL thickness was decreased in all quadrants compared with the normal-vision group (P < .001 for all comparisons). Using abnormal criteria of less than 5% and less than 1%, the area under the curve was highest for the average RNFL thickness (0.96 and 0.97, respectively) compared with specific anatomic quadrants. The highest discrimination and predictive values were demonstrated for participants with 2 or more quadrants meeting less than 5% (sensitivity = 93.3; specificity = 97.9; positive predictive value = 93.3; and negative predictive value = 97.9) and less than 1% (sensitivity = 93.3; specificity = 100; positive predictive value = 100; and negative predictive value = 98.0) criteria. CONCLUSIONS AND RELEVANCEMeasures of RNFL thickness acquired with HH-OCT during sedation can differentiate between young children with and without vision loss from OPGs. For young children who do not cooperate with vision testing, HH-OCT measures may be a surrogate marker of vision. Longitudinal studies are needed to delineate the temporal relationship between RNFL decline and vision loss.