Leptin is the primary signal through which the hypothalamus senses nutritional state and modulates food intake and energy balance1. Leptin reduces food intake by upregulating anorexigenic (appetite-reducing) neuropeptides, such as α-melanocyte-stimulating hormone2,3, and downregulating orexigenic (appetite-stimulating) factors, primarily neuropeptide Y4. Genetic defects in anorexigenic signalling, such as mutations in the melanocortin-4 (ref. 5) or leptin receptors6, cause obesity. However, alternative orexigenic pathways maintain food intake in mice deficient in neuropeptide Y7. CB1 cannabinoid receptors8 and the endocannabinoids anandamide and 2-arachidonoyl glycerol are present in the hypothalamus9, and marijuana10 and anandamide11,12 stimulate food intake. Here we show that following temporary food restriction, CB1 receptor knockout mice eat less than their wild-type littermates, and the CB1 antagonist SR141716A reduces food intake in wild-type but not knockout mice. Furthermore, defective leptin signalling is associated with elevated hypothalamic, but not cerebellar, levels of endocannabinoids in obese db/db and ob/ob mice and Zucker rats. Acute leptin treatment of normal rats and ob/ob mice reduces anandamide and 2-arachidonoyl glycerol in the hypothalamus. These findings indicate that endocannabinoids in the hypothalamus may tonically activate CB1 receptors to maintain food intake and form part of the neural circuitry regulated by leptin.

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Leptin-regulated endocannabinoids are involved in maintaining food intake

The mechanisms controlling axon guidance are of fundamental importance in understanding brain development. Growing corticospinal and somatosensory axons cross the midline in the medulla to reach their targets and thus form the basis of contralateral motor control and sensory input. The motor and sensory projections appeared uncrossed in patients with horizontal gaze palsy with progressive scoliosis (HGPPS). In patients affected with HGPPS, we identified mutations in the ROBO3 gene, which shares homology with roundabout genes important in axon guidance in developing Drosophila, zebrafish, and mouse. Like its murine homolog Rig1/Robo3, but unlike other Robo proteins, ROBO3 is required for hindbrain axon midline crossing.

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Mutations in a Human ROBO Gene Disrupt Hindbrain Axon Pathway Crossing and Morphogenesis

PURPOSE. Connective tissue structures constrain paths of the rectus extraocular muscles (EOMs), acting as pulleys and serving as functional EOM origins. This study was conducted to investigate the relationship of orbital and global EOM layers to pulleys and kinematic implications of this anatomy. METHODS. High-resolution magnetic resonance imaging (MRI) was used to define the anterior paths of rectus EOMs, as influenced by gaze direction in living subjects. Pulley tissues were examined at cadaveric dissections and surgical exposures. Human and monkey orbits were step and serially sectioned for histologic staining to distinguish EOM fiber layers in relationship to pulleys. RESULTS. MRI consistently demonstrated gaze-related shifts in the anteroposterior locations of human EOM path inflections, as well as shifts in components of the pulleys themselves. Histologic studies of human and monkey orbits confirmed gross examinations and surgical exposures to indicate that the orbital layer of each rectus EOM inserts on its corresponding pulley, rather than on the globe. Only the global layer of the EOM inserts on the sclera. This dual insertion was visualized in vivo by MRI in human horizontal rectus EOMs. CONCLUSIONS. The authors propose the active-pulley hypothesis: By dual insertions the global layer of each rectus EOM rotates the globe while the orbital layer inserts on its pulley to position it linearly and thus influence the EOM’s rotational axis. Pulley locations may also be altered in convergence. This overall arrangement is parsimoniously suited to account for numerous aspects of ocular dynamics and kinematics, including Listing’s law. (Invest Ophthalmol Vis Sci. 2000;41: 1280 ‐1290)

Evidence for active control of rectus extraocular muscle pulleys.

The stiff man syndrome (SMS) and its variants, focal SMS, stiff limb (or leg) syndrome (SLS), jerking SMS, and progressive encephalomyelitis with rigidity and myoclonus (PERM), appear to occur more frequently than hitherto thought. A characteristic ensemble of symptoms and signs allows a tentative clinical diagnosis. Supportive ancillary findings include (1) the demonstration of continuous muscle activity in trunk and proximal limb muscles despite attempted relaxation, (2) enhanced exteroceptive reflexes, and (3) antibodies to glutamic acid decarboxylase (GAD) in both serum and spinal fluid. Antibodies to GAD are not diagnostic or specific for SMS and the role of these autoantibodies in the pathogenesis of SMS/SLS/PERM is the subject of debate and difficult to reconcile on the basis of our present knowledge. Nevertheless, evidence is emerging to suggest that SMS/SLS/PERM are manifestations of an immune-mediated chronic encephalomyelitis and immunomodulation is an effective therapeutic approach. © 2002 Movement Disorder Society

Stiff man syndrome and related conditions.

Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance.

Introduction: In recent years a new perforated PDS (poly-p-dioxanon) foil (0.15 mm) has become available and has not yet been proven to be successful in reconstruction of the orbital floor after blow-out-fractures in randomized studies. The main aim of this clinical trial is to compare this new PDS foil with titanium dynamic mesh (0.3 mm) (TD), which is well established in reconstruction of the orbital floor. Patients and Methods: In a prospective multicentre randomized trial, conducted between 1997 and 1998, out of 42 patients with fractures of the orbital floor, 28 patients needing material for reconstruction were randomized to receive either PDS foil or TD. In a comprehensive preoperative and postoperative protocol patients were monitored by the surgeon, radiologist and ophthalmologist with a postoperative follow-up of least 6 months. Results: Maximum defects of the orbital floor were comparable in both groups (PDS group: 13.3 mm, TD group: 13.9 mm). In both groups the surgical procedure was well tolerated, and functional and cosmetic results were evaluated as satisfactory by all patients. Ophthalmological evaluation, performed up to 6 months postoperatively, revealed double vision or vertical strabismus in nine patients (five PDS group, four titanium group). This was not confirmed subjectively in each single patient. Also ex- or enophthalmos, registered in seven patients of the PDS and four of the TD group (mainly +/-1 mm) were not considered as relevant by the patients. Conclusion: The new 0.15 mm perforated PDS foil was comparable to 0.3 mm titanium mesh concerning functional and cosmetic outcome. Obviously, persisting ophthalmometric disorders were compensated very well in both groups. PDS foil is felt to be the preferred material since it is bioresorbable and more convenient to handle. Copyright 2001 European Association for Cranio-Maxillofacial Surgery.

Effectiveness of a new perforated 0.15 mm poly-p-dioxanon-foil versus titanium-dynamic mesh in reconstruction of the orbital floor

https://archive-ouverte.unige.ch/unige:154915/ATTACHMENT01

The Diagnostic Value of Optic Disc Evaluation in Acute Elevated Intracranial Pressure

RESULTS. In the prism experiment, the horizontal primary position of the eye not wearing the prism rotated temporally by 3.9° 6 1.7° compared with the both eyes viewing control condition. The rotation of the prism eye was in a similar range (3.4° 6 2.0°). With accommodation, the horizontal primary position of the viewing eye rotated temporally by 4.4° 6 1.4° compared with the monocular viewing control. In both the accommodation and the prism paradigms there was usually a rotation of vertical primary position downward. CONCLUSIONS. Vergence-induced changes in Listing’s plane can be independent of changes in orbital position associated with vergence. This finding supports a role for changes in central innervation in the elaboration of Listing’s law. (Invest Ophthalmol Vis Sci. 2000;41:715‐721)

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Rotation of Listing's plane with convergence: independence from eye position.

The aim of this study is to assess the functional results and morphological parameters in children surgically treated for glaucoma. Data from 43 patients and 68 eyes who were operated in our department between 1990 and 2002 were collected. This retrospective trial included primary congenital glaucoma (n=36), and secondary glaucoma (n=7) in Rieger-Axenfeld syndrome and Sturge Weber syndrome. Intraocular pressure (IOP), axial length of the eyeball, visual acuity, refractive errors and orthoptic status were analysed. The age of patients at the first surgery was 6.0±5.3 months (range 0.7 to 28.0 months). The mean period of follow-up was 57.3±36.8 months (6.0–161.0).The mean number of surgical procedures performed on one eye was 2.5±2.4 procedures (1–11). The mean IOP before the first surgery was 31.0±7.9 mmHg (17.5–52.0), and was 15.0±3.9 mmHg (7.0–28.0) at the last visit. 49 eyes (72.1%) did not need any further medical treatment after the last surgical procedure. The IOP was 18 mmHg or lower without medication in 29 eyes (42.6%) after just one surgical procedure (21 trabeculotomy, 8 combined trabeculotomy/trabeculectomy with or without mitomycin-C). At the first examination, the mean axial length of the eyeball was 22.6±1.8 mm (the mean normal value at this age is 20.3±0.7 mm), and was 24.4±2.0 mm at the last visit (the mean normal value at this age is 22.2±0.6 mm). The best corrected visual acuity at the last visit was 0.25±4.6 lines; the normal range of visual acuity at this age is from 0.4±4.0 lines to 0.8±3.0 lines. Visual acuity was 0.32 or more in 53.0% of the eyes. Visual acuity was lower than 0.1 in only 15.2% of the eyes. Myopia was present in 57.4% of the eyes with a mean spherical equivalent of −6.1±3.9 dioptres. 15 patients (34.9%) developed strabismus. 22 patients (51.2%) were treated with part-time occlusion. Binocular function as assessed with the Lang-1 test was positive in 17 of 30 patients (56.7%). Although a good long-term IOP-control can often be achieved in childhood glaucoma, the visual acuity remains below the normal range in most cases despite close orthoptic follow-up.

Long-term results of surgery in childhood glaucoma

PURPOSE. In ocular kinematics, the primary position (PP) of the eye is defined by the position from which movements do not induce ocular rotations around the line of sight (Helmholtz). PP is mathematically linked to the orientation of Listing’s plane. This study was conducted to determine whether PP is affected differently in patients with clinically diagnosed congenital (conTNP) and acquired (acqTNP) trochlear nerve palsy. METHODS. Patients with unilateral conTNP (n 25) and acqTNP (n 9) performed a modified Hess screen test. Threedimensional eye positions were recorded with dual search coils. RESULTS. PP in eyes with acqTNP was significantly more temporal (mean: 21.2°) than in eyes with conTNP (6.8°) or healthy eyes (7.2°). In the pooled data of all patients, the horizontal location of PP significantly correlated with vertical noncomitance with the paretic eye in adduction (R 0.59). Using a computer model, PP in acqTNP could be reproduced by a neural lesion of the superior oblique (SO) muscle. An additional simulated overaction of the inferior oblique (IO) muscle moved PP back to normal, as in conTNP. Lengthening the SO and shortening the IO muscles could also simulate PP in conTNP. CONCLUSIONS. The temporal displacement of PP in acqTNP is a direct consequence of the reduced force of the SO muscle. The reversal of this temporal displacement of PP, which occurs in some patients with conTNP, can be explained by a secondary overaction of the IO muscle. Alternatively, length changes in the SO and IO muscles, or other anatomic anomalies within the orbit, without a neural lesion, may also explain the difference in location of PP between conTNP and acqTNP. (Invest Ophthalmol Vis Sci. 2003;44:4282‐ 4292) DOI:10.1167/iovs.021181

http://www.vertigocenter.ch/straumann/reprints/Straumann2003a.pdf

Heimo Steffen

Papers

Effectiveness of a new perforated 0.15 mm poly-p-dioxanon-foil versus titanium-dynamic mesh in reconstruction of the orbital floor

The Diagnostic Value of Optic Disc Evaluation in Acute Elevated Intracranial Pressure

Rotation of Listing's plane with convergence: independence from eye position.

Long-term results of surgery in childhood glaucoma

Primary position and listing's law in acquired and congenital trochlear nerve palsy.