fMRI-Based Effective Connectivity in Surgical Remediable Epilepsies: A Pilot Study.

Simultaneous EEG-fMRI can contribute to identify the epileptogenic zone (EZ) in focal epilepsies. However, fMRI maps related to Interictal Epileptiform Discharges (IED) commonly show multiple regions of signal change rather than focal ones. Dynamic causal modeling (DCM) can estimate effective connectivity, i.e. the causal effects exerted by one brain region over another, based on fMRI data. Here, we employed DCM on fMRI data in 10 focal epilepsy patients with multiple IED-related regions of BOLD signal change, to test whether this approach can help the localization process of EZ. For each subject, a family of competing deterministic, plausible DCM models were constructed using IED as autonomous input at each node, one at time. The DCM findings were compared to the presurgical evaluation results and classified as: "Concordant" if the node identified by DCM matches the presumed focus, "Discordant" if the node is distant from the presumed focus, or "Inconclusive" (no statistically significant result). Furthermore, patients who subsequently underwent intracranial EEG recordings or surgery were considered as having an independent validation of DCM results. The effective connectivity focus identified using DCM was Concordant in 7 patients, Discordant in two cases and Inconclusive in one. In four of the 6 patients operated, the DCM findings were validated. Notably, the two Discordant and Invalidated results were found in patients with poor surgical outcome. Our findings provide preliminary evidence to support the applicability of DCM on fMRI data to investigate the epileptic networks in focal epilepsy and, particularly, to identify the EZ in complex cases.

ASPicDB: a database resource for alternative splicing analysis.

MOTIVATION: Alternative splicing has recently emerged as a key mechanism responsible for the expansion of transcriptome and proteome complexity in human and other organisms. Although several online resources devoted to alternative splicing analysis are available they may suffer from limitations related both to the computational methodologies adopted and to the extent of the annotations they provide that prevent the full exploitation of the available data. Furthermore, current resources provide limited query and download facilities. RESULTS: ASPicDB is a database designed to provide access to reliable annotations of the alternative splicing pattern of human genes and to the functional annotation of predicted splicing isoforms. Splice-site detection and full-length transcript modeling have been carried out by a genome-wide application of the ASPic algorithm, based on the multiple alignments of gene-related transcripts (typically a Unigene cluster) to the genomic sequence, a strategy that greatly improves prediction accuracy compared to methods based on independent and progressive alignments. Enhanced query and download facilities for annotations and sequences allow users to select and extract specific sets of data related to genes, transcripts and introns fulfilling a combination of user-defined criteria. Several tabular and graphical views of the results are presented, providing a comprehensive assessment of the functional implication of alternative splicing in the gene set under investigation. ASPicDB, which is regularly updated on a monthly basis, also includes information on tissue-specific splicing patterns of normal and cancer cells, based on available EST sequences and their library source annotation. AVAILABILITY: www.caspur.it/ASPicDB

Neurosurgical treatment of von Hippel-Lindau-associated hemangioblastomas: benefits, risks and outcome.

AIM: Von Hippel-Lindau (VHL) disease is a genetic syndrome predisposing to central nervous system (CNS) hemangioblastomas and several lesions in many organs. The cases of all VHL individuals operated on in the Neurosurgical Unit of Padua Hospital since year 2000 were reviewed in order to define which features lead to surgical treatment and to examine surgical outcome during postoperative follow-up. METHODS: The authors evaluated 20 VHL subjects (7 males and 13 females, age at surgery 32+/-10 years) who underwent 28 operations in order to remove 48 CNS hemangioblastomas and 1 endolymphatic sac tumor. Among the 49 resected lesions, 21 (42%) were cerebellar, 9 (18%) at brainstem, 19 (38%) spinal (7 cervical, 6 dorsal, 6 at cone-cauda level), and 1 (2%) endolymphatic sac tumor in the petrous bone. Patients were graduated according to Karnofsky Performance Status (KPS) at admission, at discharge and during the last follow up visit. Genetic testing revealing the presence of a VHL disease-causing mutation was a prerequisite for inclusion in the study. RESULTS: Nineteen individuals (95%) were symptomatic. Symptomatic hemangioblastomas were associated with a cyst or a syrinx in 22/27 circumstances (81%). Total removal, as confirmed by postoperative magnetic resonance imaging (MRI), was achieved in all but one lesion. Following surgery, at follow-up (38+/-20 months), patients improved their neurological status in 75% of cases, 20% remained stable and 5% worsened; 16 patients (80%) are able to carry on normal activity with or without minor symptoms, 3 patients require some grade of assistance, 1 patient died because of bronchopneumonia. CONCLUSION: VHL-associated hemangioblastomas generally affect a young adult population and can be successfully removed, either when symptomatic, or when they reach a critical volume. Microsurgery of hemangioblastomas has a favourable impact on survival and quality of life of VHL patients, although it is strongly influenced by preoperative conditions. Transient surgical complications are possible, particularly with brainstem and spinal cord hemangioblastomas.

Acquisition of surgical skills for endoscopic ear and lateral skull base surgery: a staged training programme.

SUMMARY: Endoscopic ear surgery is radically changing the treatment of several middle and inner ear pathology, but its learning presents well-known manual and technical difficulties. The aim of this paper is be to present a training programme based on a modular model of increased difficulties. The experience from 2007 to 2016 at the University Hospital of Modena and University Hospital of Verona was reviewed and analysed for further considerations and to establish stages of training. The increasing experience of expert surgeons who deal with this kind of surgery represented the main guide to establish the steps and progression of training. In addition, the potential risk of damage of vascular structures or nerves represents fundamental criteria for progression toward higher levels. Some not-mandatory skills were also suggested for stage of difficulty. Five stages of training were deemed appropriate for progressive learning of endoscopic ear and lateral skull base surgery, ranging from simple middle and external ear procedures to surgery of inner ear and internal auditory canal. Mastering of each level is suggested before attempting procedures at a higher level, in particular for procedures involving lateral skull base. Standardisation and adoption of modular incremental training are expected to facilitate improvement of otolaryngologists and neurosurgeons starting with endoscopic middle ear and lateral skull base surgery. Adherence to such a programme during the growth phase may potentially decrease the rate of complications, making the training programme safer.

[Differences in the prevalence of work related disorders among construction workers between the end of 90s and 2006]. / Differenze nella prevalenza di malattie professionali in edilizia tra la fine degli anni '90 ed il 2006.

The aim of this work is to analyse the prevalence of occupational diseases in construction industry, comparing the results of the first years of health surveillance (1996-2000) and today's situation. We compare the prevalence of occupational diseases observed in 1348 workers during the period 1996-2000 (mean age 36,4 years, DS 11,8; mean experience in construction industry 16,9 years, DS 12,3) and the one observed in 795 different workers during 2006 (mean age 38,8 years, DS 11,1; mean experience in construction industry 18 years, DS 16,6). The prevalence of occupational diseases is respectively 12.09% and 12.83%. But analysing the single pathology it's possible to observe important differences between the two groups. In the workers observed in 2006 there is a significant reduction in prevalence of hearing loss caused by chronic exposure to noise and in prevalence of vascular disease caused by hand-arm vibrations: respectively from 94,9 to 79,2 cases/1000 workers and from 6,7 to 2.6 cases/1000 workers. Musculoskeletal diseases instead are increased from 11,1 to 37,7 cases/1000 workers, showing more attention to the problem, better diagnostics ability and more recognition by public insurance agency for occupational diseases.

Expanded transcanal transpromontorial approach to the internal auditory canal and cerebellopontine angle: a cadaveric study.

The aim of this paper is to describe and evaluate the feasibility of an expanded endoscopic transcanal transpromotorial approach (ExpTTA) to the internal auditory canal and the cerebellopontine angle. To this end, we performed a cadaveric dissection study in September 2015. In total, 2 heads (4 sides) were dissected focusing on anatomical landmarks and surgical feasibility. Data from dissections were reviewed and analysed for further consideration. In all 4 sides of the cadavers the procedure was feasible. In all cadavers, it was necessary to extensively drill the temporo-mandibular joint and to calibrate the external ear canal to allow adequate room to manoeuver the instruments and optics and to comfortably access the cerebellopontine angle. In addition, thorough skeletonisation of the carotid artery and the jugular bulb were necessary for the same purpose. In conclusion, ExpTTA appeared to be successful to access the internal auditory canal and cerebellopontine angle region. Potential extensive and routine application of this type of approach in lateral skull base surgery will depend on the development of technology and surgical refinements and on the diffusion of skull base endoscopic skills among otolaryngologists and neurosurgical community.

[First aid training in collaboration with CPT and CPTA of Bergamo]. / Realizzazione di corsi di primo soccorso in collaborazione con CPT e CPTA di Bergamo.

In this work it's briefly described the experience in planning and realizing of first aid at work courses for workers of the building trade, realized by the UOOML in collaboration with CPT and CPTA of Bergamo. In particular this is a report of the activity of planning and realization of courses in the months from February till September 2004.

[Assessment of the efficiency of the first aid course among construction companies in the Province of Bergamo]. / Valutazione dell'efficacia del corso di Primo soccorso in addetti di imprese edili della bergamasca.

The aim of this project is to value, through a specific questionnaire, the effectiveness and utility of the professional training among the construction workers responsible of the First Aid. 48 construction firms, in Province of Bergamo, were examined and 100 first aid responsible were tested through to the questionnaire. The 21% of the subjects performed a practical first aid intervention. The 84% considers the professional training courses to be globally satisfactory, and one third underlines the necessity of an annual refresher course. This study tends to confirm the validity of this program of professional training, particularly in the construction trade, that is characterized by a high accidents rate.

[Efficacy of periodic health surveillance of construction workers visited at the CPT of Bergamo]. / Considerazioni sull'efficacia della sorveglianza sanitaria periodica di lavoratori edili visitati presso il CPT di Bergamo.

The aim of this work is to expose the results obtained with the application of a model about efficacy in occupational medicine proposed by ALMLII. In particular we discuss the validity of some indicators of efficacy used in a large group of construction workers during health surveillance, in order to verify effectiveness and appropriateness of an occupational medicine service, as a part of the whole prevention and safety system.

[Variation of the judgment of the fitness to specific work in a cohort study in construction industry]. / Variazione del giudizio di idoneità lavorativa alla mansione specifica in uno studio longitudinale di una popolazione edile.

This work shows the results of a study about variation of the judgement of the fitness to specific work in the construction industry in a year. In the 8.6% of the cases, after a year from the previous examination, it was necessary to express new limitations to the job activity mainly because of the presence of illness of the musculoskeletal or cardiovascular system. Considering only workers aged over 35 years, the percentage of variation after a year grows to 12.3%.

Corticospinal excitability is specifically modulated by motor imagery: a magnetic stimulation study.

Transcranial magnetic stimulation (TMS) was used to investigate whether the excitability of the corticospinal system is selectively affected by motor imagery. To this purpose, we performed two experiments. In the first one we recorded motor evoked potentials from right hand and arm muscles during mental simulation of flexion/extension movements of both distal and proximal joints. In the second experiment we applied magnetic stimulation to the right and the left motor cortex of subjects while they were imagining opening or closing their right or their left hand. Motor evoked potentials (MEPs) were recorded from a hand muscle contralateral to the stimulated cortex. The results demonstrated that the excitability pattern during motor imagery dynamically mimics that occurring during movement execution. In addition, while magnetic stimulation of the left motor cortex revealed increased corticospinal excitability when subjects imagined ipsilateral as well as contralateral hand movements, the stimulation of the right motor cortex revealed a facilitatory effect induced by imagery of contralateral hand movements only. In conclusion, motor imagery is a high level process, which, however, manifests itself in the activation of those same cortical circuits that are normally involved in movement execution.

Impaired control of an action after supplementary motor area lesion: a case study.

The kinematics of the action formed by reaching-grasping an object and placing it on a second target was studied in a patient who suffered from an acute vascular left brain lesion, which affected the Supplementary Motor Area proper (SMA-proper) (Matelli M, Luppino G. Thalamic input to mesial and superior area 6 in the macaque monkey. Journal of Comparative Neurology 1996;372:59-87, Matelli M, Luppino G, Fogassi L, Rizzolatti G. Thalamic input to inferior area 6 and area 4 in the macaque monkey. Journal of Comparative Neurology 1989;280:468-488), and in five healthy control subjects. The reach kinematics of the controls was affected by the positions of both the reaching-grasping and the placing targets (Gentilucci M, Negrotti A, Gangitano M. Planning an action. Experimental Brain Research 1997;115:116-28). In contrast, the reach kinematics of the patient was affected only by the position of the reaching-grasping target. By comparing these results with those previously found in Parkinson's disease patients executing the same action (Gentilucci M, Negrotti A. Planning and executing an action in Parkinson's disease patients. Movement Disorders 1999;1:69-79, Gentilucci M, Negrotti A. The control of an action in Parkinson's disease. Experimental Brain Research 1999;129:269-277), we suggest that the anatomical "motor" circuit formed by SMA-proper (see above), Basal Ganglia (BG) and Thalamus (Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends in the Neurosciences 1990;13:266-271, Hoover JE, Strick PL. Multiple output channels in the basal ganglia. Nature 1993;259:819-821) may be involved in the control of actions: SMA-proper assembles the sequence of the action, whereas BG updates its parameters and stores them.

Intravenous ketoprofen in renal colic: a placebo-controlled pilot study.

In a double-blind trial 30 patients with renal colic were allocated at random to receive 200 mg of ketoprofen, 1 gm of lysine acetylsalicylate, or placebo by intravenous bolus injection. The patients were asked to rate their pain at intervals within three hours of injection and to indicate on a visual analogue scale the overall pain relief obtained. Both ketoprofen and lysine acetylsalicylate proved significantly more effective than placebo, with no apparent difference between them. Complete relief of pain was obtained in seven of ten patients in each of the active treatment groups compared with only one of ten patients given placebo. No untoward events were observed in any patient.

Masseteric repetitive nerve stimulation in the diagnosis of myasthenia gravis.

OBJECTIVE: (1) to develop a method for masseteric repetitive nerve stimulation (RNS) and to obtain normative data for amplitude and area decrement of the muscle (M) response. (2) To investigate myasthenia gravis (MG) patients with masseteric RNS. Masticatory muscles are frequently affected in MG, but no RNS test is available to investigate this district. METHODS: Fifteen healthy subjects and 17 MG patients were examined. The masseteric nerve was stimulated by a monopolar needle (cathode), inserted between the mandibular incisure and the zygomatic arch, and a surface electrode (anode), on the contralateral cheek. Masseteric M response was recorded using surface electrodes on the muscle belly and below the mandibular angle. Stimuli were delivered at 3 Hz in trains of 9, at rest and after isometric effort. RESULTS: Normal subjects: mean amplitude decrement was 0.3+/-1.2% at rest, and 1.9+/-1.3% after isometric effort. PATIENTS: 15 patients (88%) were positive on masseteric RNS; in 3 of these it was the only positive RNS test. The extent of decrement observed in masseter muscle was significantly greater than in trapezius muscle. CONCLUSIONS: Masseteric RNS is a simple and well-tolerated procedure; it offers a new possibility in testing the cranial muscles in disorders of neuromuscular transmission.

Heteronymous H-reflex in temporal muscle motor units.

An electric stimulation of the masseteric nerve elicits a heteronymous H-reflex in the temporal muscle. The characteristics of this reflex response were investigated by analysis of the firing probability changes of single motor units. Eleven healthy subjects participated in the experiments. The heteronymous H-reflex of the temporal muscle was electrically elicited by stimulation of the masseteric nerve at 120% of the intensity needed for the maximal masseteric M-wave. From 8 to 24 motor units were sampled from the temporal muscle of each subject. Peri-stimulus time histograms of motor unit recordings were built with a 0.5-ms bin width. The mean firing probability was calculated for the 20 ms preceding the stimulus. The firing probability was considered increased when it exceeded the mean by 3 standard deviations. Of 104 sampled motor units, 40 motor units showed a significant increase of the firing probability, which lasted 1 ms or less in 29 of them. In 12 out of 16 motor units, a significant increase of firing probability also persisted at a lower stimulation intensity (120% of the threshold needed to elicit a masseteric M wave). These data indicate that: (1) some temporal muscle motor units are modulated by afferents from the masseter muscle, (2) the heteronymous H-reflex has a monosynaptic component, and (3) there might be a more complex than just monosynaptic organization serving the heteronymous temporal H-reflex. For the latter conclusion regarding synaptic wiring, however, PSTH studies like the present one can offer only indirect evidence, and this question could be better studied in animals.

Cryoglobulinaemic neuropathy manifesting with restless legs syndrome.

In a series of 12 patients with essential mixed cryoglobulinaemia (EMC) and peripheral neuropathy as main feature of the disease, restless legs syndrome (RLS) was a major manifestation in four women, aged 55-65 years. In one patient RLS was a presenting manifestation of the disease, and in another patient the diagnosis of EMC was made investigating RLS and polyneuropathy, although prior rheumatological symptoms were retrospectively recognized. All patients with RLS had symmetrical sensory polyneuropathy, but non-RLS patients had also other forms of peripheral neuropathy, and symmetrical sensory polyneuropathy only in two of eight cases (P=0.03). Neurophysiological study showed that sensory action potentials of the sural nerve were more often inelicitable in non-RLS patients (six of eight) than in RLS patients (none of three). Sural nerve biopsy had no distinctive features in three RLS patients, with regard to other patients with cryoglobulinaemic neuropathy. RLS seems not uncommon in cryoglobulinaemic neuropathy, and significantly associated with symmetrical sensory polyneuropathy, whereas patients with other subtypes of cryoglobulinaemic neuropathy do not develop RLS; thus, a disorder of the sensory inputs may be important in the pathogenesis of RLS. The occurrence of RLS, especially in middle-aged women, should prompt investigations for peripheral neuropathy focusing on cryoglobulinaemic neuropathy.

Motor-evoked potentials in masseter muscle by electrical and magnetic stimulation in intact alert man.

The electromyographic responses of the masseter after different types of transcranial stimulation were recorded with surface and needle electrodes. Magnetic stimulation at 4 cm lateral to the vertex on the biauricular line elicited MEPs in the contralateral masseter (latency 6.9 ms) due to activation of motor cortex or adjacent elements along the cortico-nuclear pathway. The ipsilateral responses to the same stimuli and to more lateral ones had shorter latencies and were ascribed to direct stimulation of the trigeminal nerve, probably its intracisternal portion. This was also the probable origin of the ipsilateral MEPs after both anodic and cathodic bipolar electrical stimulation at 7 and 11 cm lateral to the vertex on the biauricular line.

Hereditary sensory and autonomic neuropathy with ataxia and late onset.

We report two brothers affected by a dominantly inherited form of hereditary sensory and autonomic neuropathy (HSAN), characterized by clinical features of sensory ataxia, and by late onset in the 6th decade. Sural nerve biopsy in the proband showed almost complete loss of myelinated fibers, and relative sparing of unmyelinated fibers. This family showed an atypical presentation of HSAN, which is usually characterized by acrodystrophic manifestations of infantile or juvenile onset. Although a few reports of HSAN presenting with late onset and/or ataxia appeared, this is the first report of a family with dominant HSAN characterized by late onset sensory ataxia.

Electromyographic evaluation of the spared serratus anterior after postero-lateral thoracotomy.

Postero-lateral thoracotomy is the standard access in thoracic surgery, and can be carried out dividing or preserving the serratus anterior muscle. This last method, besides its advantages, is still a matter of discussion, in fact traction has been claimed to cause severe muscular damage equal to section. We have studied 20 patients (16 males and 4 females, mean age 63 years), who underwent postero-lateral thoracotomy sparing the serratus anterior, after 6 months from surgery, both clinically and by means of electromyography (EMG), to evaluate the functional status of the spared muscles. In 4 cases (20%) there wasn't any neurogenic damage nor clinical evidence of winging scapula; 3 cases (15%) had medium neurogenic damage. The remaining 13 (65%) cases had a medium neurogenic damage and only one patient showed a winging scapula, neverthless being able to lift the arm to shoulder level. Our data confirmed that retraction during surgery does not damage the serratus anterior, leaving a functionally valid muscle.