Neuromuscular maturation in the neonate: Combined electroneurographic and ultrasonographic study.

BACKGROUND: The combined electroneurography and muscle ultrasound examination (ENG-USM) in adult patients showed a correlation between the compound motor action potential (CMAP) and muscular thicknesses (MT). No similar studies exist regarding the neonatal period. AIM: To evaluate the correlations between the maximum compound muscle action potential (CMAP) and maximum muscle thickness (MT) in term and premature newborns versus a group of young adults, as measured by combined electroneurography-ultrasonography (ENG-USM) to assess the stages. STUDY DESIGN: Observational cohort study. SUBJECTS: We studied 36 subjects (14 premature and 11 term infants, and 11 young adults), who underwent ENG-USM of the tibialis anterioris (TA) muscle. OUTCOME MEASURES: We measured: 1) Onset-Peak (O-P) and Peak-to-Peak (P-P) maximum CMAP; 2) maximum MT; and 3) MT at the detected maximum CMAP. RESULTS: The maximum CMAP in term newborns studied was about 1/3 of the mean value measured in the adults; the differences between O-P and P-P values of the term versus premature infants were not significant. We did not find a good correlation between maximum MT and maximum CMAP in the term (r = 0.63) newborns, contrary to what was found in preterms (r = 0.95) and in young adults (r = 0.98). CONCLUSION: Our ENG-USM study shows that in newborns, the site of innervation of the neuromuscular plaque does not correspond to MT since muscle growth is related to the period of development, and depends on the progression of the nerve terminal branches that go to innervate the same muscle.

Grafting after sinus lift with anorganic bovine bone alone compared with 50:50 anorganic bovine bone and autologous bone: results of a pilot randomised trial at one year.

Our aim was to compare the outcome of implants inserted in maxillary sinuses augmented with anorganic bovine bone grafts compared with those augmented with mixed 50:50 bovine and autologous bone grafts. Twenty sinuses with 1-4mm of residual crestal height below the maxillary sinuses were randomised into two groups according to a parallel group design (n=10 in each). Sinuses were grafted using a lateral approach. In one group the grafts were 50:50 anorganic bovine bone and autologous bone and in the other anorganic bovine bone alone. After 7 months, 32 implants had been inserted. Outcome measures were survival of implants, complications, marginal changes in the height of the bone, and soft tissue variables (pocket probing depth and bleeding on probing). Probabilities of less than 0.05 were accepted as significant. No patient failed to complete the trial and no implant had failed at 1 year. There were some minor complications. After 12 months, the mean (SD) marginal bone loss (mm) was 1.06 (0.61) in the 50:50 group and 1.19 (0.53) in the anorganic bovine group. The mean (SD) values for pocket probing depth (mm) and bleeding on probing (score) were 2.49 (0.38) and 1.59 (0.82) in the 50:50 group and 2.31 (0.64) and 1.36 (0.87) in the anorganic bovine group (neither difference was significant). The present data are consistent with the hypothesis that the outcome of implants inserted in sinuses grafted with either material is comparable.

Municipal solid waste management: identification and analysis of engineering indexes representing demand and costs generated in virtuous Italian communities.

The definition and utilisation of engineering indexes in the field of Municipal Solid Waste Management (MSWM) is an issue of interest for technicians and scientists, which is widely discussed in literature. Specifically, the availability of consolidated engineering indexes is useful when new waste collection services are designed, along with when their performance is evaluated after a warm-up period. However, most published works in the field of MSWM complete their study with an analysis of isolated case studies. Conversely, decision makers require tools for information collection and exchange in order to trace the trends of these engineering indexes in large experiments. In this paper, common engineering indexes are presented and their values analysed in virtuous Italian communities, with the aim of contributing to the creation of a useful database whose data could be used during experiments, by indicating examples of MSWM demand profiles and the costs required to manage them.

Long-lasting beneficial effects of periradicular injection of meloxicam for treating chronic low back pain and sciatica.

BACKGROUND: Chronic low back pain (LBP) and sciatica can occur without obvious structural causes and are often resistant to conventional analgesic drugs. The effect of periradicular injection of meloxicam on LBP with or without a radicular component was assessed. A secondary objective of this prospective observational study was to assess the effect of meloxicam on functional recovery. METHODS: Seventy-two patients (30 men, 42 women) with LBP and/or sciatica were followed for 90 days to six years after injecting 10 mg meloxicam in 10 mL saline at each of the involved dermatomal levels. A standard verbal rating scale (VRS) from 0=no pain to 10=severe pain was used for assessing LBP before the injection of meloxicam (at baseline) and at 1, 5, 10, 30 and 60 min, and 1, 5, 15, 30 and 90 days intervals after the injection. The meloxicam injection was repeated only if the VRS score remained >3. Rescue analgesic requirements and functional activity levels were also assessed from 30-90 days after the last injection of meloxicam. RESULTS: The mean baseline LBP score was 8.60 ± 1.50 (SD) despite the use of multi-modal analgesic regimens (NSAIDs, glucocorticosteroids, paracetamol, oral opioids, gabapentanoid compounds, epidural or periradicular steroid and/or local anesthetics) as well as laser treatments and physical therapy. The majority of patients reported that their pain intensity decreased by ~50% 1-2 min after the meloxicam injection was completed. Thirty-six patients (50%) required no further injections, 25 patients (35%) required a second injection after seven days, and 11 patients (15%) required a total of three injections. After the meloxicam treatment(s), only 10 patients (14%) required "rescue" analgesia with oral NSAIDs. All patients were able to increase their level of functional activity after the meloxicam treatment(s). CONCLUSION: Periradicular injections of meloxicam (10 mg) appear to be a useful alternative to opioid and non-opiod analgesics for patients with intractable LBP due to nerve root inflammation.

Surgical treatment of neuromuscular scoliosis: current techniques.

41 consecutive patients surgically treated at Our Department by posterior only instrumented fusion from January 1995 to January 2009 were reviewed. There were 20 females and 21 males with a mean age of 15.8 years (range, 10 to 38). Diagnosis was: cerebral palsy (13 cases), Duchenne muscular dystrophy (7), spinal amyotrophy (7), myelomeningocele (5), poliomyelitis (3), Friedreich's ataxia (2), Escobar syndrome (2), Steinert's disease (1), Charcot Marie Tooth disease (1). Main scoliosis Cobb angle averaged 94.05° (range, 34° to 165°), the curve was thoracic in 19 cases, thoracolumbar or lumbar in 22 cases. Kyphosis (T5-T12) averaged 42.86° (range, 7° to 90°), lordosis was 33.57°. The fusion was extended to the lumbar tract in 23 patients, to the sacrum in the other 18. Our results showed that, in patients with neuromuscular scoliosis, posterior instrumented fusion is a safe and effective procedure and is the treatment of choice for patients with limited respiratory function, as in Duchenne muscular dystrophy and spinal muscular atrophy. The surgery should be performed as early as possible, and the extension of the fusion to the sacrum should be avoided in patients with residual walking ability.

Surgical treatment for scoliosis associated with rare disease.

This is a retrospective study of 11 patients, 7 females and 4 males, treated at Our Department for an early onset scoliosis (EOS) associated with rare syndromes with growing spinal implants (Growing Rod or VEPTR-like) from 2006 to 2011. Mean follow-up was 24 months (range, 12 to 36). The mean age at surgery was 7. Patients were affected by Escobar's syndrome (1), scoliosis associated to congenital heart disease (1), Arnold Chiari type 1 (1), syringomyelia (1), NF 1 (2), Prader-Willi syndrome (1), trisomy 8 (1), arthrogryposis (2) and spondylo-rib dysplasia (1). Each patient was studied from the genetic point of view, and were performed: brain-spine MRI, pulmonary function tests, Cardio-US and abdominal US, neuropsychiatric and neurological evaluation, C0-C2 CT scan. After first implant and lengthening procedures (11), the correction of the thoracic curve averaged 50%. Unfortunately, a little loss of correction of the lumbar curve occurred during the follow up. There were 8 post-operative complications, that required revision surgery in 2 cases. Our results confirmed the effectiveness and safety of growing spinal implants in the treatment of early-onset scoliosis in rare syndromes.

Complications incidence in the treatment of early onset scoliosis with growing spinal implants.

Early onset scoliosis (EOS) surgery based on growing spinal implants can lead to several complications. Aim of the study was to identify strategies to prevent those complications. A retrospective review was conducted to identify all pediatric patients affected by EOS surgically treated with growing rod or Vertical Expandable Prosthetic Titanium Rib (VEPTR) at our division between 2006 and 2011. Nineteen consecutive patients (8 males, 11 females; mean age 6.8 years) were included. The scoliosis was: idiopathic in 7 cases, congenital in 5, associated with congenital heart disease in 2, with syringomyelia and Arnold Chiari syndrome in 1, with neurofibromatosis type 1 (NF1) in 1, with Prader Willi syndrome in 1, with trisomy 8 in 1, with arthrogryposis in 1. Instrumentation used was: growing rod in 9 patients (dual rod construct in 8 cases, single rod in 1), VEPTR in 10 (always rib to spine construct). At a mean follow-up of 28 months (range, 12 to 55) 12 mechanical complications occurred in 8 of 19 patients treated (42.1%). Among cases treated with growing rod (9) 6 complications occurred in 4 patients (44.4%): revision was performed in 4 cases due to proximal anchors migration, in 2 cases due to a rod breakage. Among cases treated with VEPTR (10) 6 complications occurred in 4 patients (40%): revision was performed in 4 cases due to rib fracture with anchors migration, in 1 case due to vertebral anchor migration and in 1 case due to proximal and distal anchor migration. So, in our series mechanical complications rate was 42.1%. Our strategy to prevent these complications is to use hooks as proximal anchors, to avoid single rod construct and to use a brace as external support until final surgery is performed. If it's possible, is better to substitute VEPTR with a dual Growing Rod implant when patient's age and anatomy permits this.

The prevention of neural complications in the surgical treatment of scoliosis: the role of the neurophysiological intraoperative monitoring.

Iatrogenic spinal cord injury is the most feared complication of scoliosis surgery. The importance of combined somatosensory evoked potentials (SEP) and motor evoked potentials (MEP) monitoring during spine surgery is well known. The current authors retrospectively evaluated the results of neurophysiological intraoperative monitoring (IOM) in a large population of patients who underwent surgical treatment for spinal deformity. Intraoperative monitoring of SEPs and transcranial electrical stimulation MEPs (TES-MEP) was performed in 172 successive patients who underwent surgical treatment of idiopathic (128 pts), congenital (15 pts) or syndromic (29 pts) scoliosis. The first 106 patients (Group 1) underwent only SEP monitoring, while the other 66 patients (Group 2) underwent combined SEP and TES-MEP monitoring, when the technique was introduced in the current authors' institution. Halogenate anaesthesia (Sevoflurane, MAC 0.6-1.2) was performed in Group 1 cases, total intravenous anaesthesia (Propofol infusion, 6-10 mg/kg/h) in Group 2 patients. A neurophysiological "alert" was defined as a reduction in amplitude (unilateral or bilateral) of at least 50% for SEPs and of 65% for TES-MEPs compared with baseline. In Group 1, two patients (1.9%) developed postoperative neurologic deficits following surgical correction of spinal deformity, consisting of permanent paraparesis in one case and transient paraparesis secondary to spinal cord ischaemia in the other. Twelve patients presented intraoperative significant changes of neurophysiological parameters that improved following corrective actions by surgeons and anaesthesiologists, and did not show any postoperative neurologic deficits. In ten cases the alert was apparently unrelated to surgical manoeuvres or to pharmacological interventions and no postoperative neurologic deficits were noted. Considering the patients of Group 2, two patients (3.0%) presented transient postoperative neurologic deficits preceded by significant intraoperative changes in SEPs and TES-MEPs. In five cases a transient reduction in the amplitudes of SEPs (1 patient) and/or TES-MEPs (5 patients) was recorded intraoperatively with no postoperative neurologic deficits. In conclusion, in the current series of 172 patients the overall prevalence of postoperative neurologic deficit was 2.3% (4 patients). When combined SEP and TES-MEP monitoring was performed, the sensitivity and specificity of IOM for sensory-motor impairment was 100 and 98%, respectively. Combined SEP and TES-MEP monitoring must be regarded as the neurophysiological standard for intraoperative detection of emerging spinal cord injury during corrective spinal deformity surgery. Early detection affords the surgical team an opportunity to perform rapid intervention to prevent injury progression or possibly to reverse impending neurologic sequelae.

IgM monoclonal gammopathy-associated neuropathies with different IgM specificity.

BACKGROUND AND PURPOSE: Antibodies directed against myelin-associated glycoprotein (MAG) are believed to be the most frequent biologic marker of the neuropathies associated with IgM monoclonal gammopathy of undetermined significance (MGUS). The objective of this study was to examine the prevalence of antiganglioside and/or sulfatide-positive patients and their clinical findings, including therapeutic response, compared to anti-MAG-positive or seronegative patients. METHODS: We prospectively followed 46 patients with MGUS who were diagnosed in our tertiary referral centers for polyneuropathy since 1997. All patients underwent nerve conduction studies and were tested for anti-MAG, gangliosides, and sulfatide antibodies. All the anagraphic and clinical data (including symptoms, disability scale, therapy, secondary malignancy development) were recorded in a database and compared between three patients' groups (anti-MAG-positive; antiganglioside/sulfatide-positive; no reactivity). RESULTS: Anti-MAG reactivity was present in 17 (37%) patients; other 17 patients (37%) had antiganglioside/sulfatide reactivity and 12 (26%) had no reactivity. Patients with antiganglioside/sulfatide positivity, although heterogeneous by a clinical and neurophysiological point of view, had the most severe neuropathic manifestations and a higher disability score at nadir (P < 0.001). These patients had a better response to both intravenous immunoglobulin therapy and rituximab. CONCLUSIONS: Our results suggest that antiganglioside/sulfatide-positive patients form a relevant portion of patients with MGUS-associated polyneuropathy seen in tertiary care centers and should be considered in future studies on treatment response.

Emergency heart transplantation outcome: the Italian experience.

The National Program for Emergency Heart Transplantation (NP) was implemented in 2005 is managed at the national level by the Italian National Transplant Center. Patients admitted to the NP must be undergoing one of the following treatments: short-term Ventricular Assist Device (VAD); complicated medium or long-term VAD; complicated Total Artificial Heart; or mechanical ventilation associated with an Intra-Aortic Balloon Pump and Continuous Inotrope Therapy (intravenously). The aim of this study was to evaluate the NP experience from January 1, 2008, to December 31, 2009. We analyzed the number of requests (both fulfilled and not fulfilled), the timeliness of organ availability as well as graft and recipient survivals at 1 year. During the study period, 108 patients were admitted to the NP. The most frequent causes of admission were dilated cardiomyopathies (42.7%) and congenital cardiomyopathies (28.7%). Overall, whereas 12 subjects improved 65 patients underwent heart transplantation (60.2%) and 43 did not undergo surgery (39.8%) because of 31 succumbing before a heart became available. The median waiting time for heart transplantation was 3 days (range = 0.1-22), compared with median waiting time for elective heart transplantation (EHT) of 2.47 years. Graft and recipient survivals were 76.0 ± 1.06 compared with superior graft and recipient survivals for EHT during the same period (87.1 ± 2.0). However, implementation of NP has guaranteed heart availability at a short median time, thus allowing equitable management of this procedure.

Fueling the debate: Are outcomes better after posterior lumbar interbody fusion (PLIF) or after posterolateral fusion (PLF) in adult patients with low-grade adult isthmic spondylolisthesis?

STUDY DESIGN: Retrospective cohort study. CLINICAL QUESTION: Do more adult patients affected by low grade isthmic spondylolisthesis have significant clinical and radiological improvement following posterior lumbar interbody fusion (PLIF) than those who receive posterolateral fusion (PLF)? METHODS: One hundred and fourteen patients affected by adult low grade isthmic spondylolisthesis, treated with posterior lumbar interbody fusion or posterolateral fusion, were reviewed. Clinical outcome was assessed by means of the questionnaires ODI, RMDQ and VAS. Radiographic evaluation included CT, MRI, and x-rays. The results were analyzed using the Student t-test. RESULTS: The two groups were similar with respect to demographic and surgical characteristics. At an average follow-up of 62.1 months, 71 patients were completely reviewed. Mean ODI, RMDQ and VAS scores didn't show statistically significant differences. Fusion rate was similar between the two groups (97% in PLIF group, 95% in PLF group). Major complications occurred in 5 of 71 patients reviewed (7%): one in the PLIF group (3.6%), four in the PLF group (9.3%). Pseudarthrosis occurred in one case in the PLIF group (3,6%) and in two cases in PLF group (4.6%). CONCLUSIONS: In our series, there does not appear to be a clear advantage of posterior lumbar interbody fusion (PLIF) over posterolateral fusion (PLF) in terms of clinical and radiological outcome for treatment of adult low grade isthmic spondylolisthesis.

Selective thoracic surgery in the Lenke type 1A: King III and King IV type curves.

Pedicle screw fixation enables enhanced three-dimensional correction of spinal deformities and effectively shortens the distal fusion level. However, the choice of distal fusion level is still controversial in single thoracic idiopathic scoliosis with the lumbar compensatory curve not crossing the middle line (Lenke type 1 with modifier A or King type III and IV curves).The authors retrospectively analyzed 31 patients treated by segmental pedicular instrumentation alone, affected by a single thoracic adolescent idiopathic scoliosis with a compensatory lumbar curve not crossing the midline (Lenke 1A), with an average age of 16.3 years (range 10-22 years). The patients with regard to the King classification were also assessed. A statistical analysis was performed to determine whether the two groups (King III, King IV) presented differences concerning the level of the stable vertebra (SV), end vertebra (EV), and neutral vertebra (NV) and were also analyzed the results at follow-up regarding the relationships between the SV, EV, and lowest instrumented vertebra (LIV). The statistical analysis showed a significant difference between the two curve types. In the King III type curve the SV, EV, and NV appeared to be more proximal than those of the King IV type curve and the segments between the SV, EV, and NV appeared to be reduced in King III curves compared with King IV curves. At a follow-up of 3.2 years (range 2.2-5) the thoracic curve showed a correction of 58.4% (from 62.3 degrees to 26.6 degrees ) and compensatory lumbar curve an average spontaneous correction of 52.4% (from 38.1 degrees to 18.1 degrees ).The position of the LIV was shorter than the position of the SV in 30 patients (97%) with an average "salvage" of 2.1 (from 1 to 4) distal fusion levels. Four cases (13%), all affected by a King IV type curve, presented at follow-up an unsatisfactory results due to an "adding on" phenomenon. The statistical analysis confirmed that this phenomenon was correlated with The King IV curve (P = 0.043; Chi-square test) and that the only predictive parameter for its onset was the LIV-SV difference (odds ratio = 0.093; with a confidence interval of 0.008-1): every time that in King IV curve type the LIV was three or more levels shorter than the stable vertebra at follow-up the "adding on" phenomenon was present. The authors conclude that Lenke's type 1 with modifier A includes two kinds of curves, King III and King IV and that the Lenke's type 2 curves and King V with the lumbar curve not crossing the middle line have a similar behavior. Therefore, it is of authors' opinion that "the adding on phenomenon" could be prevented by more rigidly defining K. IV versus K. III curves. In Lenke's 1/2 A-K. IV/V type with the rotation of the first vertebra just below the thoracic lower EV in the same direction as the thoracic curve, and when SV and EV show more than two levels of difference, it is necessary to extend the lower fusion down to L2 or L3 (not more than two levels shorter than the SV). Whereas in Lenke's 1/2 A-K. III/V with the rotation of the first proximal vertebra of lumbar curve in the opposite direction to the thoracic apex and when SV and EV show not more than two level gap differences, the position of the lowest instrumented vertebra can be two or three levels shorter than the stable vertebra with satisfactory postoperative spinal balance. Therefore, the stable vertebra and the rotation of lumbar curve are considered to be a reliable guide for selecting the lower level of fusion.

The contribution of cerebrospinal fluid oligoclonal bands to the early diagnosis of multiple sclerosis.

BACKGROUND: McDonald Criteria (MDC) have been validated in selected patients at high risk for multiple sclerosis (MS). However, possible overdiagnosis of MS can represent critical issues in less controlled clinical settings. OBJECTIVE: To assess the contribution of oligoclonal bands (OB) to MS diagnosis in current clinical practice. METHODS: We included all the patients admitted to our Department since 2001 who had undergone diagnostic workup for a possible MS diagnosis, followed up for at least 1 year. We assessed the accuracy of MDC, OB, and two MDC definitions of dissemination in space (DIS-MRI: fulfillment of MRI criteria, DIS-OB: two MRI lesions+OB). RESULTS: We included 118 patients (median follow-up 4.0 years). Twenty-eight cases received an alternative diagnosis, whereas none of these presented OB, 43% fulfilled the DIS-MRI criteria. OB were present in 70% of the remaining 90 patients. By the end of the follow-up, 56% of the diagnoses had converted to clinically definite MS and OB showed higher accuracy than DIS-MRI fulfillment (70% vs 58%). Moreover, after 1 year and at the end of the follow-up, DIS-OB yielded a higher Specificity level in comparison with DIS-MRI. CONCLUSION: OB can improve overall diagnostic Accuracy by increasing Specificity and negative predictive value.

Thoracoplasty in the surgical treatment of adolescent idiopathic scoliosis.

A consecutive series of 40 adolescents surgically treated between 1998-2001, by posterior spinal fusion and thoracoplasty were compared with a similar group of 40 adolescents treated in the same period by posterior only segmental fusion. Clinical and radiographic analysis was performed, including the SRS-30 questionnaire and Pulmonary Function Tests (PFT). Minimum five years follow-up was requested. No statistical differences were found between the two groups in PFT's both pre-operatively and at latest follow up. Our findings suggest that thoracoplasty did not adversely affected long-term PFT's in AIS patients treated by posterior spinal fusion alone.

The IGF axis in prostate cancer.

Prostate cancer, the most frequent non-cutaneous malignancy in men from industrialized countries, is a growing medical problem, representing the second leading cause of male cancer deaths. In the last decade, converging evidence from epidemiological and biological studies suggests that the Insulin-like Growth Factor (IGF) axis is involved in the tumorigenesis and neoplastic growth of prostate cancer. Epidemiological observations indicated that circulating IGF-I levels are positively associated with the increased risk of prostate cancer. The activation of type I IGF receptor (IGF-IR) by IGF-I and/or IGF-II, has mitogenic and antiapoptotic effects on normal and malignant prostate cells. Altered expression of IGF axis components has also been reported in vitro and in animal models of prostate cancer, as well as in human prostate cancer tissue samples. In this review we address and analyze epidemiological studies, in vitro and in vivo cancer models, and human ex vivo prostate cancer researches performed to date supporting the role of IGF axis in prostate cancer.

An innovative diagnostic procedure of vertebral deformities without exposure to X-rays.

The objective of the study was to compare standard manual X-ray measurements of vertebral deformities and values obtained from the Ortelius 800. 52 Patients (41 females and 11 males: mean age 20.35 years) with adolescent vertebral deformities, was studied. The patients were evaluated with standard radiographic views and the Ortelius 800. The parameters considered for the comparison were the angles of scoliosis and kyphosis and the values of global axial deformity, shoulder asymmetry and pelvic tilt. We also evaluated the modification of pelvic/shoulder angle after surgery (this parameter allows to evaluate vertebral rotation and can be derived only from the Ortelius 800). This study allowed us to conclude that there is a perfect agreement between measurements with the Ortelius 800 and those resulting from standard x-rays. The system has also proved to have the capability of quantifying changes in vertebral rotation.

Anti-ganglioside antibodies and elevated CSF IgG levels in Guillain-Barré syndrome.

Anti-ganglioside antibody production and dysfunction of blood-cerebrospinal fluid (CSF) barrier (BCB) are frequent findings in dysimmune neuropathy patients, whereas intrathecal synthesis of immunoglobulins is still a matter of debate. We examined the CSF, immunological and electrophysiological characteristics from a cohort of patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), and from patients with other neurological diseases as control. Thirty-eight percent of GBS patients and 28% of CIDP patients had detectable serum titers of anti-ganglioside antibodies, which were associated with a high incidence of motor conduction block and increased F wave latencies. In GBS patients, but not in CIDP or control patients, there was an association between anti-ganglioside antibodies and increased CSF immunoglobulin-G (IgG) levels as determined by the IgG index. However, none of the GBS patients had CSF oligoclonal bands (OBs) or indications of intrathecal anti-ganglioside antibody synthesis. The possibility of an abnormal CSF concentration of immunoglobulins from serum through dysfunctional BCB or damaged nerve roots, and the role of serum anti-ganglioside reactivity in this process are discussed.

Extracorporeal photochemotherapy reduces the severity of Lewis rat experimental allergic encephalomyelitis through a modulation of the function of peripheral blood mononuclear cells.

Extra corporeal photochemotherapy (ECP) is an immunomodulating procedure used in several nonneurological diseases which, similarly to multiple sclerosis, are likely to be due to T-cell-mediated autoimmunity and it is probable that ECP can modulate the normal activity of peripheral blood mononuclear cells (PBMC). Using the Lewis rat experimental allergic encephalomyelitis (EAE) model of human multiple sclerosis (MS) we examined the effect of extracorporeal UV-A irradiation on psoralen-activated PBMC. In our experiment the comparison between the two groups of animals (ECP or sham-treatment) evidenced that the ECP treatment reduced the severity of EAE on clinical grounds and this result was confirmed by the pathological examination. The changes in the titers of anti-myelin antigen antibodies typical of EAE were also modulated by the procedure. Ex vivo examination evidenced a significant reduction in tumor-necrosis factor-alpha (TNF-alpha) released by PBMC after lipopolysaccharides (LPS) stimulation in culture. We conclude that ECP modifies the normal activity of PBMC during the course of EAE and it is possible that one of the anti-inflammatory mechanisms of action of ECP is correlated to a down-regulation of T-helper 1 lymphocytes activity.

Brainstem neurodegeneration correlates with clinical dysfunction in SCA1 but not in SCA2. A quantitative volumetric, diffusion and proton spectroscopy MR study.

Magnetic resonance (MR) techniques enable in vivo measurement of the atrophy of the brainstem and cerebellum in spinocerebellar ataxia type 1 (SCA1) and 2 (SCA2) patients, which is accompanied by a decrease in the concentration of N-acetyl aspartate (NAA) or of the NAA/creatine ratio in the pons and cerebellum. Mean diffusivity (D) is emerging as an additional sensitive and quantitative MR parameter to investigate brain diseases. In order to explore differences between the MR features of SCA1 and SCA2 and correlate the MR and clinical findings in the two conditions, we examined 16 SCA1 patients, 12 SCA2 patients and 20 healthy control subjects. The MR protocol included T1-weighted 3D gradient echo sequences, single-voxel proton spectroscopy of the right cerebellar hemisphere (dentate and peridentate region) and of the pons with a PRESS sequence and an external reference quantitation method, and (in nine patients with SCA1 and nine patients with SCA2) diffusion-weighted echo-planar images with reconstruction of the D maps. The patients were evaluated with the Inherited Ataxia Clinical Rating Scale (IACRS). Compared with control subjects, the SCA1 and SCA2 patients showed a decrease (P < 0.01) in the volume of the brainstem and cerebellum and in the concentration of NAA in the pons and cerebellar hemisphere, whereas D of the brainstem and cerebellum was increased. No significant difference was observed between the SCA1 and SCA2 patient groups. No correlation between cerebellar volume and dentate and peridentate NAA concentration was found in SCA1 or SCA2 patients. The volume of the brainstem, D of the brainstem and cerebellum and the concentration of NAA in the pons were correlated (P < 0.05) with the IACRS score in SCA1 but not in SCA2. This discrepancy is in line with the clinical observation that the clinical deficit has a later onset and faster progression in SCA1 and an earlier onset and slower progression in SCA2, and suggests that neurodegeneration of the brainstem is a comparatively more rapid process in SCA1. In conclusion, our study indicates that SCA1 and SCA2 substantially exhibit the same MR features. The correlation in SCA1 between clinical severity and quantitative volumetric, diffusion MRI and proton MR spectroscopy findings in the brainstem indicates that these measurements might be employed for longitudinal studies and hopefully as surrogate markers in future pharmacological trials of this condition.

Pixantrone (BBR2778) reduces the severity of experimental allergic encephalomyelitis.

Pixantrone is less cardiotoxic and is similarly effective to mitoxantrone (MTX) as an antineoplastic drug. In our study, pixantrone reduced the severity of acute and decreased the relapse rate of chronic relapsing experimental allergic encephalomyelitis (EAE) in rats. A marked and long-lasting decrease in CD3+, CD4+, CD8+ and CD45RA+ blood cells and reduced anti-MBP titers were observed with both pixantrone and MTX. In vitro mitogen- and antigen-induced T-cell proliferation tests of human and rodents cells evidenced that pixantrone was effective at concentrations which can be effectively obtained after i.v. administration in humans. Cardiotoxicity was present only in MTX-treated rats. The effectiveness and the favorable safety profile makes pixantrone a most promising immunosuppressant agent for clinical use in multiple sclerosis (MS).