Preoperative magnetic resonance and intraoperative ultrasound fusion imaging for real-time neuronavigation in brain tumor surgery.

PURPOSE: Brain shift and tissue deformation during surgery for intracranial lesions are the main actual limitations of neuro-navigation (NN), which currently relies mainly on preoperative imaging. Ultrasound (US), being a real-time imaging modality, is becoming progressively more widespread during neurosurgical procedures, but most neurosurgeons, trained on axial computed tomography (CT) and magnetic resonance imaging (MRI) slices, lack specific US training and have difficulties recognizing anatomic structures with the same confidence as in preoperative imaging. Therefore real-time intraoperative fusion imaging (FI) between preoperative imaging and intraoperative ultrasound (ioUS) for virtual navigation (VN) is highly desirable. We describe our procedure for real-time navigation during surgery for different cerebral lesions. MATERIALS AND METHODS: We performed fusion imaging with virtual navigation for patients undergoing surgery for brain lesion removal using an ultrasound-based real-time neuro-navigation system that fuses intraoperative cerebral ultrasound with preoperative MRI and simultaneously displays an MRI slice coplanar to an ioUS image. RESULTS: 58 patients underwent surgery at our institution for intracranial lesion removal with image guidance using a US system equipped with fusion imaging for neuro-navigation. In all cases the initial (external) registration error obtained by the corresponding anatomical landmark procedure was below 2 mm and the craniotomy was correctly placed. The transdural window gave satisfactory US image quality and the lesion was always detectable and measurable on both axes. Brain shift/deformation correction has been successfully employed in 42 cases to restore the co-registration during surgery. The accuracy of ioUS/MRI fusion/overlapping was confirmed intraoperatively under direct visualization of anatomic landmarks and the error was < 3 mm in all cases (100 %). CONCLUSION: Neuro-navigation using intraoperative US integrated with preoperative MRI is reliable, accurate and user-friendly. Moreover, the adjustments are very helpful in correcting brain shift and tissue distortion. This integrated system allows true real-time feedback during surgery and is less expensive and time-consuming than other intraoperative imaging techniques, offering high precision and orientation.

Integrin-mediated neurite outgrowth in neuroblastoma cells depends on the activation of potassium channels.

Electrical signals elicited by integrin interaction with ECM components and their role in neurite outgrowth were studied in two clones (N1 and N7) isolated from 41A3 murine neuroblastoma cell line. Although the two clones similarly adhered to fibronectin (FN) and vitronectin (VN), this adhesion induced neurite outgrowth in N1 but not in N7 cells. Patch clamp recordings in whole cell configuration showed that, upon adhesion to FN or VN but not to platelet factor 4 (PF4), N1 cells undergo a marked (approximately equal to 20 mV) hyperpolarization of the resting potential (Vrest) that occurred within the first 20 min after cell contact with ECM, and persisted for approximately 1 h before reverting to the time zero values. This hyperpolarization was totally absent in N7 cells. A detailed analysis of the molecular mechanisms involved in N1 and N7 cell adhesion to ECM substrata was performed by using antibodies raised against the FN receptor and synthetic peptides variously competing with the FN or VN binding to integrin receptor (GRGDSP and GRGESP). Antibodies, as well as GRGDSP, abolished adhesion of N1 and N7 clones to FN and VN, revealing a similar implication of integrins in the adhesion of these clones to the ECM proteins. However, these anti-adhesive treatments, while ineffective on Vrest of N7 cells, abolished in N1 cells the FN- or VN-induced hyperpolarization and neurite outgrowth, that appeared therefore strictly associated and integrin-mediated phenomena. The nature of this association was deepened through a comparative analysis of the integrin profiles and the ion channels of N1 and N7 cells. The integrin immunoprecipitation profile resulted very similarly in the two clones, with only minor differences concerning the alpha V containing complexes. Both clones possessed Ca2+ and K+ delayed rectifier (KDR) channels, while only N1 cells were endowed with inward rectifier K+ (KIR) channels. The latter governed the Vrest, and, unlike KDR channels, were blocked by Ba2+ and Cs+. By moving patched cells in contact with FN-coated beads, it was shown that KIR channel activation was responsible for the FN-mediated hyperpolarization of Vrest. Treatment with Pertuxis toxin (PTX) abolished this hyperpolarization and neurite outgrowth, indicating that a G protein is interposed between integrins and KIR channels and that the activation of these channels is required for neuritogenesis. In fact, the block of KIR channels by Cs+ abolished both hyperpolarization and neurite outgrowth, provided that the cation was supplied during the first two hours after N1 cell contact with FN.(ABSTRACT TRUNCATED AT 400 WORDS)

Distal humeral septic non-union treated with debridement and vascularized fibular transfer: case report and review of the literature.

Clinical management of a septic non-union of the distal humerus is challenging and is complicated by the diversity of potential treatments which are variably successful. We report a novel and very successful treatment of a 58-year-old man presenting an infected non-union of the right distal humerus, secondary to a closed fracture initially treated with two anatomic plates. After hardware removal, a two-stage reconstruction was performed. Bone and soft-tissue debridement was performed, followed by vascularized fibular transfer and free iliac bone crest chips fixed with plates and screws. Consolidation was achieved within three months, and a very good elbow function was presented two years thereafter. This technique shows great promise for improved management of large segmental infected bone defects of complete articular distal humeral fractures, above many currently recognized treatments.

Mother with amyotrophic lateral sclerosis and daughter with Creutzfeldt-Jakob disease.

OBJECTIVE: To describe a mother who had autopsy-proved amyotrophic lateral sclerosis and her daughter who had clinically diagnosed Creutzfeldt-Jakob disease. DESIGN: Case reports with molecular genetic analyses. SETTING: A tertiary care center. PATIENTS: The mother had progressive upper and lower motor neuron symptoms and signs starting at the age of 54 years. Electrophysiological testing supported the diagnosis of amyotrophic lateral sclerosis. Autopsy results confirmed the diagnosis. Her daughter had received injections of human growth hormone prepared from pooled human pituitary glands as a child. At the age of 31 years, she experienced the onset of gait ataxia and dysarthria. Cerebrospinal fluid showed the 14-3-3 protein. Cognitive difficulties ensued. She progressed to a nearly akinetic and mute state. She had overt visible fasciculations and muscle atrophy in the legs. MAIN OUTCOME MEASURES AND RESULTS: Neither patient carried a mutation in the prion protein gene. Both were homozygous for methionine at the polymorphic codon 129. Neither patient carried a deletion of the 5 exons of the superoxide dismutase 1 gene. CONCLUSIONS: It is uncertain whether the 2 cases occurred in the same family by chance or whether the patients shared genetic risk factors for the 2 diseases. The possibility that homozygosity at codon 129 is a risk factor for amyotrophic lateral sclerosis is being tested in a case-control study.

A prospective study of preferences and actual treatment choices in ALS.

OBJECTIVE: To determine whether ALS patients' preferences for ameliorative or life-extending technologies elicited early in the disease were related to later treatment choices. METHODS: In this prospective cohort study, 121 patients were seen at a tertiary ALS care center and followed for a median of 12 months. At baseline, patient preferences for use of tracheostomy and percutaneous endoscopic gastrostomy (PEG) placement were elicited. All patients received the same educational information before being interviewed about treatment preferences. Patients were then followed to determine if patients who viewed the interventions favorably at baseline were significantly more likely to use the interventions over follow-up. RESULTS: Six to twelve percent of patients were certain they wanted tracheostomy and 28.2% wanted PEG. Preferences were related to later treatment choices: 20% of patients who found tracheostomy acceptable had one in the follow-up period, compared with 3.4% of those not in favor (p < 0.001). For PEG, similar findings were obtained: 48.5% who initially found it acceptable had PEG, versus 8.1% of those not in favor of this treatment (p < 0.001). Patients who found the interventions acceptable were more likely to be recently diagnosed, expressed greater attachment to life, and showed greater declines in pulmonary function over follow-up. CONCLUSIONS: Patients with ALS were able to express their preferences for life-extending or ameliorative technologies and made choices consistent with these preferences. However, patient preferences may change over time, and clinical education efforts are required throughout the course of disease.

Impact of spirituality and religiousness on outcomes in patients with ALS.

The Project of Death in America Study at Columbia Presbyterian Medical Center enrolled 121 patients with ALS from 1996 through 1997, 46 of whom participated in a study assessing the effects of religiousness and spirituality (attachment to life, mental health, support group, health care proxy, and attitudes toward death) on outcomes (technology and death). Spirituality or religion influenced use of percutaneous endoscopic gastrostomy, noninvasive assisted ventilation, tracheotomy, and attitudes toward the dying process.

Response to fibronectin-integrin interaction in leukaemia cells: delayed enhancing of a K+ current.

In murine erythroleukaemia cells, the response of ion channels was followed before and after contact with fibronectin-coated latex microspheres. Patch-clamp experiments in 'whole-cell' and in 'cell-attached' configurations showed that cell adhesion to fibronectin promoted plasma membrane hyperpolarization mediated by activation of potassium channels that were indistinguishable from calcium-dependent potassium channels K(Ca) in these cells. K+ current increase began in 5-6 min and was completed about 10 min after the first contact. The timecourse of this process recorded from 'whole-cell' was very similar to that followed in intact cells by observing the increase of single channel currents. The open probability of single channels in the patch increased after contact, revealing that this activation is propagated at distance from the adhesion site. The slow onset of the effect suggests the presence of a complex regulatory pathway between fibronectin-integrin binding and activation of potassium channels. Decreasing cytoplasmic free Ca2+ concentration to pCa 9 diminished, but did not inhibit, the response. The current induced by fibronectin was not blocked by apamin, alpha-charybdotoxin or glibenclamide, but was abolished by high concentrations of tetraethylammonium (TEA). These data suggest for the first time the existence of a specific regulative connection between integrin receptors and ionic channels.

Incidence and predictors of PEG placement in ALS/MND.

In the Project on Death in America ALS cohort, 121 patients were followed to examine the timing of key milestones in the course of the disease, such as tracheostomy and PEG placement. During the 2- to 4-year follow-up period, 26.5% of patients received PEG, yielding a cumulative incidence of 48%. PEG placement occurred, on average, 16 months after patients received confirmation of the diagnosis at our Center. Patients who received PEG were more likely to have tracheostomies than patients not using PEG (p<0.01). In multivariate proportional hazard models that included both sociodemographic and disease indicators, the strongest predictor of PEG use was a patient's baseline preference for PEG: 57.1% of patients "absolutely in favor" went on to have PEG, compared to only 9.3% of those "absolutely against" (p<0.01). PEG users were more likely to have initiated health care proxies. These findings suggest that patients who use PEG may be consistently proactive in the face of the disease.

Prospective study of palliative care in ALS: choice, timing, outcomes.

To understand palliative care choices among people with ALS, it is important to follow a group of recently diagnosed patients and record when patients reach well-defined palliative care milestones. We began following such a cohort prospectively in 1996, when 121 ALS patients were enrolled from a tertiary care clinic. These patients are assessed every 4 months to determine their experience with ameliorative and palliative care. Domains include adjuvant therapies (e.g. speech therapy), adaptive aids (e.g. wheelchair use, augmentative communication), home health care, PEG placement, pulmonary support, health care directives, psychosocial care (e.g. participation in support group, pastoral counseling), and hospitalization. The median follow-up time for the cohort, to date, was 12 months. In the group that entered the cohort within 1 year of their diagnosis (n=93), 53.8% have died, 22.6% have had PEG, 19.4% have used Bi-PaP, and 4.3% have had a tracheostomy. Many patients did not take advantage of palliative care options before death; for example, 36.6% used hospice, 48% had signed a power of attorney form, and 18% had 'do not resuscitate' orders in their medical charts. Examining time to such endpoints captures important features of patient and family experience with the disease.

Identification of a novel mutation in Cu/Zn superoxide dismutase gene associated with familial amyotrophic lateral sclerosis.

We report a new missense mutation (Ala140Gly) in exon 5 of the Cu/Zn superoxide dismutase (SOD-1) gene in a 73-year-old man with familial amyotrophic lateral sclerosis (FALS). The enzymatic activity of mutated SOD-1 measured in erythrocyte lysate was 70% of control. This heterozygote mutation, which is associated with the late onset of the disease, is located in the active site of the enzyme.

The clinical impact of dynamic intraventricular obstruction during dobutamine stress echocardiography.

We selected 73 consecutive patients without myocardial-infarction, hypertrophic cardiomyopathy or hypertension complaining of effort chest discomfort/dyspnoea, and/or reporting exercise ischaemic ECG changes, and submitted them to simultaneous dobutamine stress echocardiography (DSE) and 99mTc tetrofosmin SPECT (T SPECT) and to coronary angiography to evaluate the clinical impact of intraventricular obstruction (IVO) during dobutamine infusion. Sixteen patients (22%, 7 males, mean age+/-SD 63+/-8 years, group 1) developed IVO (mean CW Doppler velocity+/-SD: 3.8+/-1.0 m/s) and 57 (41 males, mean age+/-SD 63+/-10 years, group 2) did not. The two groups had similar incidence of angina and ischaemic ECG changes at exercise tolerance test. DSE did not demonstrate wall motion abnormalities in any group 1 patient while T SPECT showed a perfusion defect in the only one with coronary artery disease (CAD). DSE reproduced symptoms in a higher percentage of patients with than without IVO, while there was no statistical difference in the reproduction of ischaemic ECG changes, despite CAD prevalence was much lower in group 1. Group 1 patients remained asymptomatic on beta-blockers at 12-month follow-up. Dobutamine-induced IVO, by reproducing symptoms, suggests that IVO plays a role in the clinical setting in patients without CAD complaining of unexplained reduced effort tolerance who should undergo DSE.

Echocardiographic diagnosis of coronary sinus type atrial septal defect. A case report.

BACKGROUND: Coronary sinus type atrial defect is the result of an incomplete formation of the atriovenous fold. This is a rare anomaly that in a very few cases took advantage of echocardiographic diagnosis before surgery. We report on a case of coronary sinus type atrial septal defect diagnosed by means of transthoracic and transesophageal echocardiography. PATIENT: A 65 year old woman who was admitted to hospital for evaluation of dyspnea and pre-syncope. A diagnosis of secundum type atrial septal defect had been achieved few months before. METHOD DESCRIPTION: Color Doppler transthoracic echocardiography demonstrated evidence of left-to-right shunt through the coronary sinus-left atrium common wall, while transesophageal echocardiography showed a defect in the coronary sinus roof in its terminal portion, proximal to the atrial septum. At that level the shunt flow was demonstrated by the presence of a negative contrast after contrast injection. Both transthoracic and transesophageal contrast echocardiographies demonstrated the persistence of a left superior vena cava draining into the enlarged coronary sinus: the existence of a right-to-left shunt at the coronary sinus level suggested by transthoracic echocardiographic examination was not confirmed by transesophageal echocardiography. CONCLUSIONS: This is one of the few reported cases of coronary sinus type atrial defect diagnosed noninvasively and the diagnostic usefulness of both transthoracic and transesophageal echocardiographic approaches is stressed.

Contralateral spinal accessory nerve: a suitable "new" donor nerve for heterotopic nerve transfer in total brachial plexus palsy.

Patients with complete brachial plexus palsy with avulsion of 4-5 roots often have a paucity of suitable donor nerves to provide for a proper functional recovery of the upper extremity. The spinal accessory nerve is routinely employed ipsilaterally for nerve transfer to the suprascapular nerve. The purpose of this paper is to describe the clinical use of the contralateral spinal accessory nerve as a donor nerve for brachial plexus surgery. Since 2005 the contralateral spinal accessory nerve has been used for neurotization of the axillary nerve in selected cases of total brachial plexus injuries. In this paper total plexus palsy surgical strategies, technical details and preliminary functional outcomes of a group of 6 consecutive patients with a minimum follow-up of 30 months (76-31, average 55) are described. The preliminary results are encouraging: the functional outcome of the deltoid muscle, evaluated according to the British Medical Research Council grading system, was M4 in 1 patient, M3 in 1 patient, M2 in 2 patients, M1 in 1 patient, and M0 in 1 patient. In conclusion, the use of the contralateral spinal accessory nerve shows good results in terms of functional recovery and the simplicity of the procedure.

Efficiency of Hyaloglide in the prevention of the recurrence of adhesions after tenolysis of flexor tendons in zone II: a randomized, controlled, multicentre clinical trial.

Hyaloglide is a hyaluronan-based gel based on a novel auto-crosslinked technology designed to reduce postsurgical adhesions. Its efficacy was assessed in a multicentred randomized controlled trial comparing the results of flexor tenolysis in zone 2 following failed flexor tendon repairs. In the control group a standard release was performed. In the treated group, Hyaloglide was applied into the flexor sheath and around the site of tenolysis. Forty-five patients, 19 controls and 26 treated with Hyaloglide, were enrolled in 13 centres. All the patients were evaluated at 30, 60, 90 and 180 days after surgery by testing Total Active Motion, Quick-DASH questionnaire and number of working days lost after surgery. Patients in the Hyaloglide group had a statistically better recovery of finger motion at all time intervals and returned earlier to work and daily activities. The use of Hyaloglide did not appear to increase the complication rate.

Prevalence of depressive disorders and change over time in late-stage ALS.

OBJECTIVE: To determine the prevalence of depressive disorders and symptoms in patients with late-stage ALS, to identify possible risk and protective factors associated with depression, and to determine whether depression increases as death approaches. METHODS: Semistructured interviews were conducted monthly with hospice-eligible patients with ALS and caregivers until the study endpoints of death or tracheostomy. Standardized measures were administered to assess depressive disorders and symptoms, hopelessness, spiritual beliefs, attitudes toward hastened death, quality of life, and related constructs. RESULTS: Sixty-three percent of eligible patients were enrolled. Of the 80 participants, 17 were seen only once; the number of monthly assessments for the others ranged from 2 to 18. For the 53 patients who died, median interval between last assessment and death was 30 days. At study baseline, 81% had no depressive disorder, 10% had minor depression, and 9% had symptoms consistent with major depression. Diagnoses of depression were made on 16% of 369 monthly assessments. Fifty-seven percent of patients never had a depression diagnosis at any visit, and 8% were depressed at all visits. There was no trend toward increasing depression as death approached. Presumed protective factors including spiritual beliefs, spouse as care partner, financial situation, depression in caregiver, and hospice participation did not distinguish between those who were depressed and those who were not. CONCLUSIONS: Results of multiple measures of depression and distress converged to indicate that major depression in people with late-stage ALS is rare, although transient depressive symptoms may occur, and depression does not generally increase as death approaches.