Laser-Evoked Potentials to Pudendal Stimulation in Healthy Subjects: A Pilot Study.

PURPOSE: Laser-evoked potentials (LEPs) are useful neurophysiological tools for investigating the A-delta sensory peripheral fibers and the central nociceptive pathway. The current investigation aims to obtain normative values of LEPs via pudendal nerve stimulation in healthy adult volunteers. METHODS: Laser-evoked potentials were recorded in 16 men and 22 women, 22 to 75 years of age, using neodymium and yttrium and aluminum and perovskite laser bilateral stimulation to the pudendal nerve-supplied skin and the dorsal surface of the hands and feet. We assessed the perceptive threshold, latency, and amplitude of the N1 component and main vertex N2-P2 complex. The relationship between gender, age, height, and site of stimulation was statistically analyzed. RESULTS: Both in men and in women, laser perceptive threshold increased from genitalia to foot and from hand to foot (P ≤ 0.001). N1 and N2-P2 latencies progressively increased from pudendal area to hand to foot (P ≤ 0.008). N1 and N2-P2 complex LEP amplitudes progressively decreased from hand to genitalia to foot (P ≤ 0.04). The latencies of N1 component and N2-P2 complex of LEPs correlated with body height, whereas the amplitude of the N2-P2 complex correlated negatively with age; no correlations were observed between the latencies and amplitudes with gender. CONCLUSIONS: This study provides normative data on pudendal LEPs versus hand and foot LEPs. Incorporation of pudendal LEPs into clinical practice could provide a valuable neurophysiological tool for the study of pelvic pain syndromes.

Health-related quality of life in clinically isolated syndrome and risk of conversion to multiple sclerosis.

BACKGROUND AND OBJECTIVES: A few studies have found that low scores on self-rated health and quality of life measures are associated with following worsening disability in multiple sclerosis (MS). We wanted to estimate the association between self-rated quality of life scores among patients with clinically isolated syndrome (CIS) and the risk of subsequent conversion to definite MS. METHODS: One hundred sixty-two patients from the GERONIMUS cohort with a symptom or sign suggestive of MS and without a definite diagnosis of MS at the time of inclusion were asked to evaluate their health-related quality of life according to MSQoL-54 scale. They were clinically assessed and mood and depression scales were applied. The association between the scores of these scales and the risk of converting to definite MS during a 5-year follow-up was estimated using the Cox- proportional hazard regression model. RESULTS: Quality of life at examination was significantly lower compared to those of an age- and sex-adjusted general Italian population. During the follow-up, 116 patients (72%) converted to definite MS. No significant predictive effects were found for the summary scales of MSQol-54 or other scales. The estimates did not change after adjusting for age, sex, BMI, education, MRI findings, Expanded Disability Status Scale (EDSS) score, and treatment at time of examination. CONCLUSION: Persons with CIS in this cohort reported reduced self-rated quality of life compared to the general population, but variation in these scores was not associated with subsequent conversion from CIS to clinical definite MS.

Intraoperative neurophysiological monitoring for intradural extramedullary spinal tumors: predictive value and relevance of D-wave amplitude on surgical outcome during a 10-year experience.

OBJECTIVEThe purpose of this study was to evaluate the technical feasibility, accuracy, and relevance on surgical outcome of D-wave monitoring combined with somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) during resection of intradural extramedullary (IDEM) spinal tumors.METHODSClinical and intraoperative neurophysiological monitoring (IONM) data obtained in 108 consecutive patients who underwent surgery for IDEM tumors at the Institute for Scientific and Care Research "ASMN" of Reggio Emilia, Italy, were prospectively entered into a database and retrospectively analyzed. The IONM included SSEPs, MEPs, and-whenever possible-D-waves. All patients were evaluated using the modified McCormick Scale at admission and at 3, 6, and 12 months of follow-up .RESULTSA total of 108 patients were included in this study. A monitorable D-wave was achieved in 71 of the 77 patients harboring cervical and thoracic IDEM tumors (92.2%). Recording of D-waves in IDEM tumors was significantly associated only with a preoperative deeply compromised neurological status evaluated using the modified McCormick Scale (p = 0.04). Overall, significant IONM changes were registered in 14 (12.96%) of 108 patients and 9 of these patients (8.33%) had permanent loss of at least one of the 3 evoked potentials. In 7 patients (6.48%), the presence of an s18278 caudal D-wave was predictive of a favorable long-term motor outcome even when the MEPs and/or SSEPs were lost during IDEM tumor resection. However, in 2 cases (1.85%) the D-wave permanently decreased by approximately 50%, and surgery was definitively abandoned to prevent permanent paraplegia. Cumulatively, SSEP, MEP, and D-wave monitoring significantly predicted postoperative deficits (p = 0.0001; AUC = 0.905), with a sensitivity of 85.7% and a specificity of 97%. Comparing the area under the receiver operating characteristic curves of these tests, D-waves appeared to have a significantly greater predictive value than MEPs and especially SSEPs alone (0.992 vs 0.798 vs 0.653; p = 0.023 and p < 0.001, respectively). On multiple logistic regression, the independent risk factors associated with significant IONM changes in the entire population were age older than 65 years and an anterolateral location of the tumor (p < 0.0001).CONCLUSIONSD-wave monitoring was feasible in all patients without severe preoperative motor deficits. D-waves demonstrated a statistically significant higher ability to predict postoperative deficits compared with SSEPs and MEPs alone and allowed us to proceed with IDEM tumor resection, even in cases of SSEP and/or MEP loss. Patients older than 65 years and with anterolateral IDEM tumors can benefit most from the use of IONM.

Intraoperative Neurophysiological Monitoring in Surgical Treatment of Spinal Dural Arteriovenous Fistulas: Technique and Results.

OBJECTIVE AND BACKGROUND: Data on intraoperative neurophysiological monitoring (IOM) during surgery of spinal dural arteriovenous fistulas (SDAVFs) are lacking. The purpose of this study was to evaluate the role of IOM during microsurgery for SDAVFs. MATERIALS AND METHODS: From March 2007 to March 2013, 12 patients had microsurgery with IOM for SDAVFs. The IOM included somatosensory-evoked potentials, motor-evoked potentials (MEPs), and - in selected cases - D-Waves. All patients were evaluated at admission and at follow-up (6, 12, and 24 months) with Aminoff-Logue Disability Scale for Gait-Aminoff-Logue Disability Scale (G-ALS) and Micturition-Aminoff-Logue Disability Scale (M-ALS). STATISTICAL ANALYSIS USED: Logistic regression was used for detecting the clinical risk factors influencing neurological functions after the treatment. RESULTS: During surgery, we registered the absence of significant modifications of evoked potentials in nine cases (75%), while improvement of MEPs occurred in three cases (25%). No false-negative case was registered, and IOM predicted the absence of new postoperative neurological deficit in all patients. At 24-month follow-up, nine patients improved their overall neurological status, while three patients remained stable. At univariate analysis, Aminoff-Logue Disability Scales for Gait and Micturition (G + M-ALS) score at 24-month follow-up was directly associated with the duration of symptom before the surgery (P = 0.024), preoperative G-ALS (P = 0.02), M-ALS (P = 0.022), and G + M-ALS scores (P = 0.045), and improvement of IOM after occlusion of the fistula (P = 0.025). CONCLUSIONS: In our series, no significant worsening of evoked potentials occurred and subsequently the surgical strategy was not changed by IOM. However, no false-negative case was registered, and IOM predicted the absence of new postoperative neurological deficit in all patients. Patients with improvement of IOM parameters after occlusion of the fistula had greater chances of postsurgical improvement at the univariate analysis.

First-line disease-modifying drugs in relapsing-remitting multiple sclerosis: an Italian real-life multicenter study on persistence.

OBJECTIVE: The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for relapsing-remitting multiple sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. The aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months. Secondary aims were to compare the time to discontinuation and the reasons for discontinuation between the two groups and to explore the demographic and clinical factors associated with DMD discontinuation. METHODS: In this prospective, multi-center, real-life observational study, patients commencing any first-line DMD between 1 January 2015 and 31 July 2016 were enrolled and followed up for at least 12 months or until the drug was discontinued. RESULTS: Of the 520 included patients, 262 (49.6%) started an injectable and 258 (50.4%) an oral DMD. There was no difference in the proportion of patients on oral (n = 62, 24%) or on injectable (n = 60, 23%) DMDs discontinuing treatment, the most frequent reason being adverse events/side-effects. Higher baseline Expanded Disability Status Scale (EDSS) scores and younger age increased the odds of treatment withdrawal. Time to treatment discontinuation was not different between the two groups and was not influenced by the initiated DMD (oral versus injectable), even after adjustment for baseline differences. CONCLUSION: The route of administration alone (i.e. oral versus injectable) was not a significant predictor of persistence with first-line DMDs in RRMS.

Definitive childlessness in women with multiple sclerosis: a multicenter study.

The frequency of definitive childlessness in women with multiple sclerosis (MS) may be higher than in the general population. MS may also affect decisions on the delivery procedure and on breast-feeding issues. Aim of the study was to assess the frequency of childlessness and its possible causes, the proportion of cesarean deliveries (CD), and the frequency of breast-feeding in patients and controls who have reached the end of their reproductive period. Female MS patients (>43 years) and controls (>45 years) filled out a questionnaire. We enrolled 303 patients and 500 controls. MS was associated with a higher frequency of childlessness (22 vs 13%) and less patients were in a stable relationship (83 vs 89%). There was no difference in the reported rates of infertility and miscarriages, while elective abortions were more frequent in patients (20 vs 12%). MS did not significantly affect the frequency of CD or of breast-feeding. MS-related reasons for childlessness, reported by 16% of childless patients, included disability/fear of future disability, fear of genetically transmitting MS, fear of not starting/discontinuing treatments, and discouragement by physician. Definitive childlessness is more frequent in women with MS compared to controls. A portion of voluntary childlessness may be avoided through correct/tailored information to patients.

Intraoperative neurophysiological monitoring for intradural extramedullary tumors: why not?

BACKGROUND: While intraoperative neurophysiological monitoring (IOM) for intramedullary tumors has become a standard in neurosurgical practice, IOM for intradural extramedullary tumors (IDEMs) is still under debate. The aim of this study is to evaluate the role of IOM during surgery for IDEMs. METHODS: From March 2008 to March 2013, 68 patients had microsurgery with IOM for IDEMs (31 schwannomas, 25 meningiomas, 6 ependymomas of the cauda/filum terminalis, 4 dermoid cysts and 2 other lesions). The IOM included somatosensory evoked potentials (SEPs), motor evoked potentials (MEPs), and--in selected cases--D-waves. Also preoperative and postoperative neurophysiological assessment was performed with SEPs and MEPs. All patients were evaluated at admission and at follow up (minimum 6 months) with the Modified McCormick Scale (mMCs). RESULTS: Three different IOM patterns were observed during surgery: no change in evoked potentials (63 cases), transitory evoked potentials change (3 cases) and loss of evoked potentials (2 cases). In the first setting surgery was never stopped and a radical tumor removal was achieved (no stop surgery group). In 3 cases of transitory evoked potentials change, surgery was temporarily halted but the tumors were at the end completely removed (stop and go surgery group). In 2 more patients the loss of evoked potentials led to an incomplete resection (stop surgery group). No patients presented a worsening of the pre-operative clinical conditions (at admission 47 patients presented mMCs 1-2 and 21 patients mMCs 3-5, while at follow up 62 patients are mMCS 1-2 and 6 patients mMCs 3-5). CONCLUSIONS: In our series significant IOM changes occurred in 5 out of 68 patients with IDEMs (7.35%), and it is conceivable that the modification of the surgical strategy - induced by IOM - prevented or mitigated neurological injury in these cases. Vice versa, in 63 patients (92.65%) IOM invariably predicted a good neurological outcome. Furthermore this technique allowed a safer tumor removal in IDEMs placed in difficult locations as cranio-vertebral junction or in antero/antero-lateral position (where rotation of spinal cord can be monitored) and even in case of tumor adherent to the spinal cord without a clear cleavage plane.

Previous treatment influences fingolimod efficacy in relapsing-remitting multiple sclerosis: results from an observational study.

OBJECTIVE: Fingolimod (FTY) is licensed as a disease-modifying treatment in highly active relapsing-remitting multiple sclerosis. The aim of the study was to evaluate the efficacy and safety of FTY in a real-life setting and to explore the possible role of clinical and MRI parameters, including previous treatment type, in predicting its efficacy. METHODS: Clinical and MRI data was collected on 127 patients assigned to treatment with FTY in six multiple sclerosis centers in Emilia-Romagna, Italy, between August 2011 and June 2013. RESULTS: During a mean follow-up period of 10 months (range 1-22), we observed a total of 47 relapses in 39 patients (30.7%); new T2 lesions or gadolinium-enhancing (Gd+) lesions were present at follow-up MRI in 32/71 patients (45%). Expanded disability status scale (EDSS) at the end of the follow-up period was not different when compared to the baseline EDSS. Serious adverse events occurred in three patients (2.4%). A higher proportion of patients previously treated with natalizumab showed clinical (41%) or MRI activity (54%). Previous treatment with natalizumab increased the risk of a relapse within 30 days (versus immunomodulatory drugs; OR: 4.3; p = 0.011) and at survival analysis (versus remaining patients; HR: 1.9; p = 0.046). Study limitations include a small population sample, a short observation period with variable timing of follow-up MRI and different baseline characteristics of patients previously treated with natalizumab compared to those treated with immunomodulatory drugs. CONCLUSIONS: This study confirms the efficacy of FTY in reducing relapse rate in patients previously treated with immunomodulatory drugs, while it seems to be less effective in patients discontinuing natalizumab. Due to the short duration of follow-up it is not possible to evaluate disability progression; however, no difference was observed between the groups.

Risk of multiple sclerosis following clinically isolated syndrome: a 4-year prospective study.

The aim of the study was to estimate the rate of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and to investigate variables predicting conversion in a cohort of patients presenting with symptoms suggestive of MS. Patients with a first symptom suggestive of MS in the preceding 6 months and exclusion of other diseases were enrolled in an observational prospective study from December 2004 through June 2007. Conversion from CIS to MS according to both McDonald and Clinically Defined Multiple Sclerosis (CDMS) criteria was prospectively recorded until March 2010. The multivariate Cox proportional hazard model was used to assess the best predictive factors of conversion from CIS to MS. Among 168 patients included in the analysis, 122 converted to MS according to McDonald criteria whereas 81 converted to MS according to CDMS criteria. The 2-year probability of conversion was 57% for McDonald Criteria and 36% for CDMS criteria. Variables at enrolment significantly associated with conversion according to McDonald criteria were age and positivity for Barkhof criteria, and according to Poser's CDMS criteria, age, positivity for Barkhof criteria and no disease modifying therapy. In this large prospective cohort study the conversion rate from CIS to MS in patients presenting with recent symptoms suggestive of MS was within the range of previous observational studies and lower than that reported in the placebo arm of randomized trials. We confirm the prognostic value of MRI in addition to the previous experimental data on the protective role of disease-modifying therapies.

Atypical Wernicke's encephalopathy showing lesions in the cranial nerve nuclei and cerebellum.

Wernicke's encephalopathy (WE) is a severe neurological disorder caused by a dietary deficiency of Vitamin B1 and characterized by consciousness changes, ocular abnormalities, and ataxia. Wernicke's encephalopathy is considered a medical emergency and treatment consists of intravenous thiamine administration. Typically in alcoholic and nonalcoholic patients magnetic resonance shows alterations in the mamillary bodies, medial thalami, tectal plate, and periaqueductal regions. We report here on a nonalcoholic atypical case of WE which presented with reversible symmetrical lesions in the cranial nerves nuclei and in the cerebellum alongside the classic neuroradiological findings.

A novel point mutation in PMP22 gene in an Italian family with hereditary neuropathy with liability to pressure palsies.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant inherited disorder characterized by recurrent sensory or motor dysfunction. In 85% of HNPP cases the genetic defect is a 1.4 Mb deletion on chromosome 17p11.2, encompassing the PMP22 gene. Point mutations in the PMP22 gene responsible for HNPP phenotypes are rare. We investigated a 17-years-old girl who led to our detecting a novel mutation in PMP22 gene. The mutation was also detected in her father and corresponded to a deletion of one tymidine at position 11 in exon2 (c.11delT). This novel mutation creates a shift on the reading frame starting at codon 4 and leads to the introduction of a premature stop at codon 6.

The multiple sclerosis functional composite: different practice effects in the three test components.

BACKGROUND: The multiple sclerosis functional composite (MSFC) is a multidimensional, MS-specific outcome measure for use in clinical trials, comprising three tests: timed 25-foot walk (T25FW), paced auditory serial addition (PASAT), and 9-hole peg (9HP). OBJECTIVE: To assess interrater and intrarater reliability and practice/fatigue effects in the MSFC. METHODS: The MSFC was administered by two neurologists after a formal training session to 32 MS outpatients. Patients were assessed four times by one examiner and twice by the other. The six tests were administered in a single day, with at least 20 min of rest between them. The examiners were blinded to the results of previous assessments. Testing order was random. RESULTS: Interrater reliability was excellent, with intraclass correlation coefficients (ICC) ranging from 0.93 for 9HP (95% confidence interval [CI] 0.84-0.96) to 0.99 for T25FW (95% CI 0.97-0.99). For intrarater reliability, ICC ranged from 0.93 for PASAT (95% CI 0.82-0.97) to 0.98 for T25FW (95% CI 0.93-1.00). We found no practice effect for T25FW after the first administration. However, performance improved with testing over the first three sessions for PASAT and over the first four sessions for 9HP. CONCLUSIONS: The MSFC is characterised by excellent reliability. Practice effects for the three MSFC components differed, being negligible for T25FW and evident for PASAT and 9HP. To improve efficiency, we suggest one prebaseline administration of T25FW, three of PASAT and four of 9HP.