Pathogenesis of vestibular schwannoma in ring chromosome 22

<p>Abstract</p> <p>Background</p> <p>Ring chromosome 22 is a rare human constitutional cytogenetic abnormality. Clinical features of neurofibromatosis type 1 and 2 as well as different tumour types have been reported in patients with ring chromosome 22. The pathogenesis of these tumours is not always clear yet.</p> <p>Methods</p> <p>We report on a female patient with a ring chromosome 22 presenting with severe mental retardation, autistic behaviour, café-au-lait macules and facial dysmorphism. Peripheral blood lymphocytes were karyotyped and array CGH was performed on extracted DNA. At the age of 20 years she was diagnosed with a unilateral vestibular schwannoma. Tumour cells were analyzed by karyotyping, array CGH and <it>NF2 </it>mutation analysis.</p> <p>Results</p> <p>Karyotype on peripheral blood lymphocytes revealed a ring chromosome 22 in all analyzed cells. A 1 Mb array CGH experiment on peripheral blood DNA showed a deletion of 5 terminal clones on the long arm of chromosome 22. Genetic analysis of vestibular schwannoma tissue revealed loss of the ring chromosome 22 and a somatic second hit in the <it>NF2 </it>gene on the remaining chromosome 22.</p> <p>Conclusion</p> <p>We conclude that tumours can arise by the combination of loss of the ring chromosome and a pathogenic <it>NF2 </it>mutation on the remaining chromosome 22 in patients with ring chromosome 22. Our findings indicate that patients with a ring 22 should be monitored for NF2-related tumours starting in adolescence.</p

Modeling complex metabolic reactions, ecological systems, and financial and legal networks with MIANN models based on Markov-Wiener node descriptors

[Abstract] The use of numerical parameters in Complex Network analysis is expanding to new fields of application. At a molecular level, we can use them to describe the molecular structure of chemical entities, protein interactions, or metabolic networks. However, the applications are not restricted to the world of molecules and can be extended to the study of macroscopic nonliving systems, organisms, or even legal or social networks. On the other hand, the development of the field of Artificial Intelligence has led to the formulation of computational algorithms whose design is based on the structure and functioning of networks of biological neurons. These algorithms, called Artificial Neural Networks (ANNs), can be useful for the study of complex networks, since the numerical parameters that encode information of the network (for example centralities/node descriptors) can be used as inputs for the ANNs. The Wiener index (W) is a graph invariant widely used in chemoinformatics to quantify the molecular structure of drugs and to study complex networks. In this work, we explore for the first time the possibility of using Markov chains to calculate analogues of node distance numbers/W to describe complex networks from the point of view of their nodes. These parameters are called Markov-Wiener node descriptors of order kth (Wk). Please, note that these descriptors are not related to Markov-Wiener stochastic processes. Here, we calculated the Wk(i) values for a very high number of nodes (>100,000) in more than 100 different complex networks using the software MI-NODES. These networks were grouped according to the field of application. Molecular networks include the Metabolic Reaction Networks (MRNs) of 40 different organisms. In addition, we analyzed other biological and legal and social networks. These include the Interaction Web Database Biological Networks (IWDBNs), with 75 food webs or ecological systems and the Spanish Financial Law Network (SFLN). The calculated Wk(i) values were used as inputs for different ANNs in order to discriminate correct node connectivity patterns from incorrect random patterns. The MIANN models obtained present good values of Sensitivity/Specificity (%): MRNs (78/78), IWDBNs (90/88), and SFLN (86/84). These preliminary results are very promising from the point of view of a first exploratory study and suggest that the use of these models could be extended to the high-throughput re-evaluation of connectivity in known complex networks (collation)

Outcome after surgery in supratentorial and infratentorial solitary brain metastasis

BACKGROUND: The aim of this retrospective study was to investigate and compare the outcome after surgery in patients with a supratentorial solitary metastasis (SSM) and an infratentorial solitary metastasis (ISM). A worse prognosis has been reported in ISM. METHODS: Fifty-two patients with a newly diagnosed solitary brain metastasis on MRI were included to identify risk factors affecting the outcome. Key variables included tumor size, staging of the primary tumor, time span of presurgical work-up, and surgical technique. Outcome variables included postoperative complications, tumor recurrence, and mortality. Kaplan-Meier survival analysis was applied. RESULTS: Thirty patients with a SSM and 22 patients with an ISM underwent gross total resection. The tumor size did not have a statistical significant effect on survival. Presurgical work-up time was similar in SSM and ISM. Postoperative complications were more frequently encountered in ISM. Recurrence rate was comparable in SSM and ISM. Carcinomatous meningitis (CM) was more frequently seen in ISM, and CM was seen more often with the piecemeal resection technique. There was no statistical difference in overall survival between SSM and ISM. CONCLUSIONS: This study identified factors that play a role in the outcome after surgery in patients with ISM and SSM on MRI. Postoperative complications seemed to be higher in ISM and CM was more often seen in ISM, but the worse prognosis in patients with ISM compared with SSM could not be confirmed.status: publishe

Maternal-fetal surgery for myelomeningocele: some thoughts on ethical, legal, and psychological issues in a Western European situation

The results of the Management of Myelomeningocele Study (MOMS) randomized controlled trial have demonstrated that maternal-fetal surgery (MFS) for myelomeningocele (MMC) compared to postnatal MMC repair has clear neurological benefits for the child at 12 and 30 months of age. Level I evidence nevertheless does not provide answers to many questions in this delicate field. Since the beginning of 2012, our fetal center has been offering MFS for spina bifida aperta (SBA) to patients from different European and non-European countries, in a societal context where termination of pregnancy is the option chosen by most patients when being informed of this diagnosis.status: publishe

Cutaneous reflex modulation and self-induced reflex attenuation in cerebellar patients

BACKGROUND AND AIM: Modulation of cutaneous reflexes is important in the neural control of walking. It has extensively been studied, but knowledge about underlying neural pathways is still incomplete [1]. Recent animal studies have suggested that the cerebellum is important for the modulation of cutaneous reflexes during gait [2]. Other studies in humans have shown that such reflexes can be attenuated when stimulation is self-induced and it was suggested that the cerebellum is important for this [3]. Here, we evaluated these cutaneous reflex features in cerebellar patients. METHODS: We analyzed cutaneous reflex activity during walking, both in patients with a focal cerebellar lesion and in healthy controls. We recorded electromyography bilaterally in the tibialis anterior, gastrocnemius medialis and biceps femoris muscles. Stimuli were applied to the sural nerve at the ankle. Reflex modulation patterns were compared between groups. Additionally, we compared reflexes after standard (computer-triggered) stimuli to reflexes after self-induced stimuli in both groups. Self-induced stimuli were triggered by the participants through pressing a handheld button. RESULTS: Cutaneous reflex modulation patterns were similar between healthy controls and cerebellar patients, but cerebellar patients were less able to attenuate reflexes to self-induced stimuli in the tibialis anterior muscle of the stimulated leg. In healthy controls, these reflexes to self-induced stimuli were more often attenuated than in the patient group, mainly at the end of the stance phase and during the swing phase. CONCLUSIONS: The results suggest that the cerebellum is important in anticipation of the consequences of motor actions but that it has probably no major role in cutaneous reflex modulation in humans. REFERENCES: 1. Zehr EP & Stein RB. Prog Neurobiol 58: 185-205, 1999 2. Pijpers A, et al. J Neurosc 28: 2179-2189, 2008 3. Baken BC, et al. J Physiol 570: 113-124, 2006status: publishe

The role of the cerebellum in cutaneous reflex modulation and self-induced reflex attenuation

Modulation of cutaneous reflexes is important in the neural control of walking. It has extensively been studied, but knowledge about underlying neural pathways is still incomplete. Recent animal studies have suggested that the cerebellum is important for the modulation of cutaneous reflexes during gait. Other studies in humans have shown that such reflexes can be attenuated when stimulation is self-induced and it was suggested that the cerebellum is important for this. Here, we evaluated these cutaneous reflex features in cerebellar patients. We analyzed cutaneous reflex activity during walking, both in patients with a focal cerebellar lesion and in healthy controls. We recorded electromyography bilaterally in the tibialis anterior, gastrocnemius medialis and biceps femoris muscles. Stimuli were applied to the sural nerve at the ankle. Reflex modulation patterns were compared between groups. Additionally, we compared reflexes after standard (computer-triggered) stimuli to reflexes after self-induced stimuli in both groups. Self-induced stimuli were triggered by the participants through pressing a handheld button. Cutaneous reflex modulation patterns were similar between groups, but cerebellar patients were less able to attenuate reflexes to self-induced stimuli in the tibialis anterior muscle of the stimulated leg. In healthy controls, these re exes to self-induced stimuli were more often attenuated than in the patient group, mainly at the end of the stance phase and during the swing phase. The results suggest that the cerebellum is important in anticipation of the consequences of motor actions but that it has probably no major role in cutaneous reflex modulation in humans.status: accepte

Complications of skull reconstruction after decompressive craniectomy

Decompressive craniectomy can be a life-saving procedure. Later reconstruction of the skull using the stored bone flap ("cranioplasty") is often associated with complications. These complications require new procedures and often result in the reconstruction of the skull using an expensive patient-specific cranial implant.peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=tacb20status: publishe

Choroidal fissure cerebrospinal fluid-containing cysts: case series, anatomical consideration, and review of the literature

Cerebrospinal fluid (CSF)-containing cysts at the level of the choroidal fissure are rare embryological entities infrequently described in the literature because of their benign nature. On the occasion of a case series, we present an overview of the literature and discuss anatomical and embryological location, imaging characteristics, presenting symptoms, and treatment indication of these lesions.status: publishe

Dynamic gait stability in cerebellar patients

Cerebellar damage in humans has often been associated with balance problems. Such associations are frequently based on measures like step width and variability in temporal gait parameters. However, increases in those measures do not necessarily imply that stability of gait is decreased. Therefore, we evaluated a more direct measure of dynamic gait stability in cerebellar patients. Thirteen patients were included who all displayed chronic focal lesions after cerebellar tumor resection. Both the cerebellar patients and nine healthy controls walked on an instrumented treadmill at 1.0 m/s for three minutes. We used 150 strides to calculate the short-term maximum Lyapunov exponent from the medio-lateral displacement of a marker cluster placed at the sacrum. The cerebellar patients displayed relatively mild functional deficits (ICARS = 7.4 ± 5.9, range 0-19). The patients had a lower overground walking speed as compared to healthy controls (1.11 m/s versus 1.28 m/s). The short-term maximum Lyapunov exponent was higher in cerebellar patients, indicating reduced dynamic stability of gait. Alternatively, classic measures as step width, stride time variability and the margin of stability were similar between patients and controls. Additionally, no significant correlation was observed between any of the tested measures within the patient group, except for a correlation between step width and margin of stability (p < 0.0001). It is concluded that the short-term maximum Lyapunov exponent constitutes a valuable sensitive measure to evaluate stability in case of mild instability.status: accepte