Fabio Papacci

A Scan of Chromosome 10 Identifies a Novel Locus Showing Strong Association with Late-Onset Alzheimer Disease

Strong evidence of linkage to late-onset Alzheimer disease (LOAD) has been observed on chromosome 10, which implicates a wide region and at least one disease-susceptibility locus. Although significant associations with several biological candidate genes on chromosome 10 have been reported, these findings have not been consistently replicated, and they remain controversial. We performed a chromosome 10–specific association study with 1,412 gene-based single-nucleotide polymorphisms (SNPs), to identify susceptibility genes for developing LOAD. The scan included SNPs in 677 of 1,270 known or predicted genes; each gene contained one or more markers, about half (48%) of which represented putative functional mutations. In general, the initial testing was performed in a white case-control sample from the St. Louis area, with 419 LOAD cases and 377 age-matched controls. Markers that showed significant association in the exploratory analysis were followed up in several other white case-control sample sets to confirm the initial association. Of the 1,397 markers tested in the exploratory sample, 69 reached significance (P

Recurrent Ventriculoperitoneal Shunt Infection Caused by Small-Colony Variants of Staphylococcus aureus

Phenotypic variants of Staphylococcus aureus may be misidentified by routine microbiological methods, and they may also respond poorly to antibacterial treatment. Using molecular methods, we identified small-colony variants of methicillin-resistant S. aureus (which were misidentified by 3 widely used automated identification systems as methicillin-susceptible coagulase-negative staphylococci) as the cause of recurrent ventriculoperitoneal shunt-related meningitis.

Long‐term follow‐up of patients with cardiac syndrome X treated by spinal cord stimulation

Objective: To assess the long-term effect of spinal cord stimulation (SCS) in patients with refractory cardiac syndrome X (CSX). Methods: A prospective, controlled, long-term follow-up was performed of 19 patients with CSX with refractory angina who underwent SCS (SCS group, 5 men, mean (SD) age 60.9 (8.5) years); 9 comparable patients with CSX who refused SCS treatment (3 men, mean (SD) age 60.9 (8.8) years) constituted the control group. Clinical and functional status were assessed at the time of screening for SCS indication (basal evaluation) and at a median (range) follow-up of 36 (15–82) months. Results: The two groups at baseline did not show any difference in clinical characteristics and angina status. All indicators of angina status (angina episode frequency, duration and short-acting nitrate use) improved significantly at follow-up in the SCS group (p<0.001) but not in controls. Functional status, as assessed by the Seattle Angina Questionnaire and a visual analogue scale for quality of life, improved at follow-up in the SCS group (p<0.001 for all scales) but not in controls. Exercise tolerance, exercise-induced angina and ST segment changes also significantly improved in the SCS group but not in controls. Conclusions: Data show that SCS can be a valid form of treatment for long-term control of angina episodes in patients with refractory CSX.

Comparison of descending volleys evoked by transcranial and epidural motor cortex stimulation in a conscious patient with bulbar pain

OBJECTIVEnTo compare the pattern of activation of motor cortex produced by transcranial magnetic stimulation and epidural electrical stimulation.nnnMETHODSnThe spinal volleys evoked by transcranial magnetic stimulation and epidural electrical stimulation over the cerebral motor cortex were recorded from an electrode inserted into the cervical epidural space of one conscious subject who also had a cortical epidural electrode over the motor area. The volleys were termed D- and I-waves according to their latency. Magnetic stimulation was performed with a figure-of-eight coil and the induced current flowed either in a postero-anterior (PA) or in latero-medial (LM) direction.nnnRESULTSnAt active motor threshold intensity LM magnetic stimulation evoked a D wave whereas PA stimulation evoked an I(1) wave with later I waves being recruited at increasing stimulus intensities. Electrical epidural stimulation evoked both a D wave and I waves. However, the D wave evoked by electrical epidural stimulation had a longer latency than the LM D wave, suggesting either a more proximal site of activation of the pyramidal axon or activation of slightly faster conducting set of corticospinal fibres by LM stimulation. The I3 wave evoked by electrical epidural stimulation also had a longer latency than the PA I3-wavennnCONCLUSIONSnEpidural stimulation of the motor cortex can produce repetitive excitation of corticospinal neurones. The order of recruitment of the volleys, and the latency of the D and I3 waves may be slightly different to that seen after transcranial magnetic stimulation.nnnSIGNIFICANCEnOur findings suggest that there may be subtle differences in the populations of neurones activated by the two forms of stimulation.

Advances in diagnosis and treatment of trigeminal neuralgia

Various drugs and surgical procedures have been utilized for the treatment of trigeminal neuralgia (TN). Despite numerous available approaches, the results are not completely satisfying. The need for more contemporaneous drugs to control the pain attacks is a common experience. Moreover, a number of patients become drug resistant, needing a surgical procedure to treat the neuralgia. Nonetheless, pain recurrence after one or more surgical operations is also frequently seen. These facts reflect the lack of the precise understanding of the TN pathogenesis. Classically, it has been related to a neurovascular compression at the trigeminal nerve root entry-zone in the prepontine cistern. However, it has been evidenced that in the pain onset and recurrence, various neurophysiological mechanisms other than the neurovascular conflict are involved. Recently, the introduction of new magnetic resonance techniques, such as voxel-based morphometry, diffusion tensor imaging, three-dimensional time-of-flight magnetic resonance angiography, and fluid attenuated inversion recovery sequences, has provided new insight about the TN pathogenesis. Some of these new sequences have also been used to better preoperatively evidence the neurovascular conflict in the surgical planning of microvascular decompression. Moreover, the endoscopy (during microvascular decompression) and the intraoperative computed tomography with integrated neuronavigation (during percutaneous procedures) have been recently introduced in the challenging cases. In the last few years, efforts have been made in order to better define the optimal target when performing the gamma knife radiosurgery. Moreover, some authors have also evidenced that neurostimulation might represent an opportunity in TN refractory to other surgical treatments. The aim of this work was to review the recent literature about the pathogenesis, diagnosis, and medical and surgical treatments, and discuss the significant advances in all these fields.

Long-term motor cortex stimulation for amyotrophic lateral sclerosis

BACKGROUNDnMotor cortex stimulation has been proposed for treatment of amyotrophic lateral sclerosis (ALS) and preliminary studies have reported a slight reduction of disease progression using both invasive and noninvasive repetitive stimulation of the motor cortex.nnnOBJECTIVEnThe aim of this proof of principle study was to investigate the effects of motor cortex stimulation performed for a prolonged period (about 2 years) on ALS progression.nnnMETHODSnTwo patients were included in the study; the first patient was treated with monthly cycles of repetitive transcranial magnetic stimulation (rTMS) and the second one was treated with chronic epidural motor cortex stimulation. The rate of progression of the disease before and during treatment was compared.nnnRESULTSnThe treatments were well tolerated by the patients. Both patients deteriorated during treatment; however, the patient treated with rTMS showed a slight reduction in deterioration rate.nnnCONCLUSIONSnAlthough we cannot be sure whether the effects observed in the patient treated with rTMS can be attributed to this form of stimulation, our study set the groundwork for possible future studies investigating the effects of rTMS, for a prolonged period, on a larger group of ALS patients.

Intramedullary thrombosed venous ectasia mimicking hemangioblastoma.

A 24-year-old female patient was admitted to our department because of 2 weeks history of progressive weakness and loss of sensation of lower limbs. One month before, the patient experienced an episode of intense low back pain treated with analgesic drugs. On admission, neurological examination showed severe weakness and loss of sensation of lower limbs, urinary incontinence, hyper-reflexia and signs of spasticity of lower extremities. A spinal cord magnetic resonance imaging (MRI) with gadolinium showed a rounded well-defined intramedullary mass at level of conus medullaris with a probably anterior extension toward ventral surface of the cord (Fig. 1a–d); these findings suggested a vascular tumor such as hemangioblastoma. Patient underwent a T12-L1 laminectomy with split of the posterior longitudinal sulcus and, under neurophysiological monitoring, total removal of lesion that showed a well-defined plane of cleavage and appeared as a hard and black mass on intra-operative view. Histological examination revealed a thin external fibrous wall containing a fibrino-hematic collection, with no evidence of neoplastic cells. The external wall appeared green after Masson s trichrome stain, suggesting the presence of collagen fibers; a layer of granulation tissue, with numerous capillary blood vessels, labeled by anti-CD31 antibody immunostaining, was present underneath the capsule; more internally an abundant meshwork of fibrin and erythrocytes, with evidence of a central lumen recently endothelized by a thin endothelial layer was observed (Fig. 1e–g). No labeled cells with glial fibrillary acid protein or S-100 protein antibody immunostaining were observed. The diagnosis was venous ectasia with recent thrombosis and partial organization. Postoperative course was uneventful; patient experienced a slow but constant improvement of neurological status at 6month follow-up. A postoperative spinal cord MRI showed the complete removal of the lesion without any other pathological findings. In our case, the diagnosis of a vascular tumor such as hemangioblastoma was suggested by the MRI appearance of the lesion whose findings were compatible with those reported in the literature [1]. As MRI findings were strongly suggestive for a hemangioblastoma, and patient s clinical conditions were rapidly worsening, angiography was considered to be unnecessary in the workup of the patient, as indicated by Chu et al. [1]. Nevertheless, the acute clinical onset and rapid progression of symptoms were

The role of preoperative angiography in the management of giant meningiomas associated to vascular malformation.

Background: The role of preoperative digital subtraction angiography (DSA) in meningiomas is currently under discussion because of the introduction of noninvasive magnetic resonance imaging (MRI) angiography to study vascular anatomy associated to the tumor. Preoperative DSA is mainly performed to obtain embolization of the lesion, although a number of complications have been reported after this procedure. Nonetheless, the coexistence of meningiomas with vascular malformations has previously been reported and it has been evidenced that this event could be underestimated because of neglect of preoperative DSA. Here, we report on two challenging cases of giant meningiomas associated to vascular malformations and we discuss the pertinent literature. Case Descriptions: In the first case: A large right temporal meningioma with erosion of the sphenoid greater wing and extension toward infratemporal fossa and right orbit - a large pseudoaneurysm of right middle cerebral artery branch was found end embolized during DSA. In the second case: A giant parieto-temporal meningioma - DSA permitted the full visualization of an abnormal drainage of superior sagittal sinus like a “sinus pericranii” that was respected during the following surgery. Conclusion: We think that MRI angiography is the exam of choice to study vascular anatomy in meningiomas. Nonetheless, DSA remains a useful tool in giant meningiomas not only to embolizate the lesion but also to treat tumor associated vascular malformation and to achieve the full knowledge of vascular anatomy. We think that a wide communication between interventionalist and surgeon is essential for the optimal management of these patients.

The Importance of Stimulation Cycle in Vagus Nerve Stimulation for Drug-Resistant Epilepsies- Our Experience and Literature Review

The impact of stimulation cycle on the outcome of patients submitted to vagal nerve stimulation (VNS) has been only marginally investigated in the literature. Nonetheless this is an important factor in term of tolerability of side effects, duration of generator and costs of therapy. Here the role of this parameter was evaluated on 21 patients who underwent to VNS implant at our Institution from January 1994 to February 2011 and responded to VNS (they reported a stable decrease of seizure number at least of 50%). We studied 3 stimulation cycles: slow (30’’on-5’off), intermediate (30’’on-3’off), fast (7’’on-20’’off). Each cycle was 1 year in duration. The stimulation cycle was recorded at the latest available follow-up (FU) for each patient (mean FU was 80.42 ± 54.01 months). Our protocol was to start with the slow cycle, to switch to the fast cycle and then to the intermediate one. The mean seizure frequencies before VNS and at latest FU were 26.08 ± 29.73 and 7.54 ± 10.22, respectively (p<0.0001; Wilcoxon Signed Rank Test). At latest FU, 11 cases (52.38%) were using the slow cycle and 8 (38.09%) the intermediate one. Among patient with a FU longer than 3 years (n=16), 15 of them (93.75%) were using slow or intermediate cycles. When considering the subgroup of patients with a 75% of reduction of number of crisis (n=12) nobody was using the fast cycle. Our results indicate that in patients responding to VNS the slow and intermediate cycles maintain the benefit of stimulation. If there is no response with these two cycles the probability of become a responder with the fast cycle is low.

PTMS18 Amyotrophic lateral sclerosis: effects of prolonged motor cortex stimulation

Objectives: To investigate inter-individual variation in the efficiency of BST with regard to the stimulation site. Methods: We studied 31 healthy subjects, using a right hand muscle as a recording site. Three stimulation sites were compared: BST over the inion (inion BST), and BST over the midpoint between the inion and the right (ipsilateral BST) or left (contralateral BST) mastoid process. Five suprathreshold BSTs were performed for each stimulation site using the same stimulation intensity. The mean peak-to-peak amplitudes of MEP were compared. The active motor threshold (AMT) and onset latency for inion BST and ipsilateral BST were also measured and compared. Results: Contralateral BST did not evoke discernible MEPs in most subjects. In 21 subjects (67.7%), ipsilateral BST elicited larger MEPs than inion BST, and AMT for ipsilateral BST was lower than or equal to the AMT for inion BST in all subjects. Ipsilateral BST elicited shorter latency in such subjects, when MEP amplitudes were adjusted. Conclusions: The suitable stimulation site for BST differed among subjects. About two-thirds showed larger MEP to ipsilateral BST. Efficient stimulation site needs to be searched before the main examination.