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Objective The main objective is to investigate the diagnostic accuracy and the relation of touch sensation and subjective sensory symptoms in the medial aspect of the hand dorsum, and neurography of the dorsal ulnar cutaneous nerve (DUCN) in ulnar neuropathy at the elbow (UNE). Secondary objective is to report the electrophysiological occurrence of anatomical variant of sensory innervation of the medial aspect of the hand dorsum from superficial radial nerve (SRN). Design Prospective, cohort study. Setting Electromyography laboratory. Participants Consecutive participants (N=282), those with UNE (n=81) and those without UNE (n=201), were enrolled. Interventions Not applicable. Main Outcome Measures Accuracy and agreement between sensory clinical findings of the medial hand dorsum and neurography of DUCN in UNE diagnosis. Results DUCN neurographic and sensory findings had high specificity and relatively low sensitivity. Normal or abnormal sensory nerve action potential (SNAP) of DUCN matched with normal or abnormal touch sensation of the medial aspect of hand dorsum. Abnormal DUCN SNAP was related to the clinical severity of UNE and to the axonal damage of the ulnar nerve. Anatomical variant of the innervation of hand dorsum from SRN was demonstrated in 31 of 564 hands (6.2%) belonging to 26 of 282 participants (9.2%). If the variant was present, DUCN SNAP of the same side was more frequently absent or of low amplitude. Conclusions The utility of DUCN neurography and sensory findings of the medial aspect of the dorsum of the hand is limited in the diagnosis of UNE. However, if DUCN SNAP is absent or low in amplitude, it is advisable to check the presence of the anatomical variant of the innervation of the medial aspect of the hand dorsum from SRN.

Objective Previous studies showed "F-wave inversion" (F-INV) as a sensitive method in the electrodiagnosis of early stage of carpal tunnel syndrome (CTS). This study aimed at evaluating the sensitivity and specificity of F-wave and nerve conduction velocity (NCV) testing in CTS. Methods We consecutively enrolled 244 cases and 108 controls. F-waves analysis included: Fwave minimum and mean latencies, F-wave persistence and chronodispersion, mean-F/CMAP amplitude ratio, F-INV. Specificity and sensitivity of F-waves parameters were calculated in the whole sample of CTS patients and by grouping the patients according to CTS severity. Multivariate logistic regression was also performed using F-INV as a dependent variable. Results In the whole sample the sensitivity of F-mean-INV and of median–ulnar NCV comparative testing was 50.8% and 93.7%, respectively. F-INV sensitivity dropped to 8% in CTS early stage. F-INV could be predicted only by distal motor latency of the median nerve. The sensitivity of all F-wave parameters increased only in the most severe stages of CTS. Conclusions This study does not confirm the electrodiagnostic usefulness of F-INV in early stage of CTS. All F-wave parameters, including F-INV, are much less sensitive than conventional NCV in CTS electrodiagnosis. F-wave does not add further useful information specifically related to CTS.

Summary Study aim This prospective study aim to examine whether clinical findings and electrodiagnostic testing (EDX) in patients with lumbosacral monoradiculopathy due to herniated disc (HD) differ as a function of root involvement level (L5 vs. S1) and HD zone (paramedian vs. intraforaminal). Patients and methods All patients with L4, L5 or S1 monoradiculopathy were prospectively enrolled at four electromyography (EMG) labs over a 2-year period. The diagnosis was based on a congruence between patient history and MRI evidence of HD. We compared the sensitivities of clinical findings and EDX with respect to both root involvement level and HD zone. Multivariate logistic regression was performed in order to verify the association between abnormal EMG, clinical, and neuroradiological findings. Results One hundred and eight patients (mean age 47.7 years, 55% men) were consecutively enrolled. Sensory loss in the painful dermatome was the most frequent finding at physical examination (56% of cases). EMG was abnormal in at least one muscle supplied by femoral and sciatic nerves in 45 cases (42%). Inclusion of paraspinal muscles increased sensitivity to only 49% and that of proximal muscles was useless. Motor and sensory neurography was seldom abnormal. The most frequent motor neurographic abnormalities were a delay of F-wave minimum latency and decrease in the compound muscle action potential amplitude from extensor digitorum brevis and abductor hallucis in L5 and S1 radiculopathies, respectively. Sensory neurography was usually normal, the amplitude of sensory nerve action potential was seldom reduced when HD injured dorsal root ganglion or postganglionic root fibres. Multivariate logistic regression analysis showed that EMG abnormalities could be predicted by myotomal muscular weakness, abnormal deep reflexes, and paraesthesiae. The only clinical and electrophysiological differences with respect to root involvement level concerned deep reflexes and motor neurography of deep peroneal and tibial nerves. Conclusions Only some EDX parameters are helpful for the diagnosis of lumbosacral radiculopathy. EMG was abnormal in less than 50% of cases and its abnormalities could be predicted by some clinical findings. However, neurography is useful as a tool for differential diagnosis between radiculopathy and more diffuse disorders of the peripheral nervous system (polyneuropathy, plexopathy).

Objective Breast cancer is the most common female cancer in Morocco. About 5 to 10% are due to hereditary predisposition and mutations in BRCA1 and BRCA2 genes are responsible for an important proportion of high-risk breast/ovarian cancer families. The relevance of BRCA1 /2 mutations in the Moroccan population was not studied. The main objective of this study is to investigate the spectrum of BRCA1 and BRCA2 germline mutations in early onset and familial breast/ovarian cancer among Moroccan women. Methods We screened the entire coding sequences and intron/exon boundaries of BRCA1 and BRCA2 genes in 40 patients by direct sequencing. Results Nine pathogenic mutations were detected in ten unrelated families, five deleterious mutations in BRCA1 gene and four mutations in BRCA2 gene. Four novel mutations were found: one in BRCA1 (c.2805delA/2924delA) and three in BRCA2 (c.3381delT/3609delT; c.7110delA/7338delA and c.7235insG/7463insG). We also identified 51 distinct polymorphisms and unclassified variants (three described for the first time). Conclusions Our data suggest that BRCA1 and BRCA2 mutations are responsible for a significant proportion of familial breast cancer in Moroccan patients. Therefore full BRCA1 /2 screening should be offered to patients with a family history of breast/ovarian cancer.

Objective Carpal tunnel syndrome (CTS) has a high prevalence in agricultural workers, especially those engaged in vineyards. We postulated that vineyard CTS was electrophysiologically different from CTS of other subjects. We performed a retrospective cross-sectional electrophysiological study of two cohorts of consecutive patients with CTS, the first consisting of vineyard workers and the second, of other unselected types of workers, housewives and pensioners. Methods Thirty-three vineyard workers (mean age 46.8 years, 42% women) and 205 patients with other occupations (mean age 53.7 years; 66% women) were enrolled. All patients underwent sensory and motor neurography of the median and ulnar nerves. Differences in demographic and electrophysiological findings between groups were calculated and multiple linear regression analysis was performed to eliminate the influence of potential confounding factors (age, sex, BMI, clinical severity of CTS) on the results of univariate difference analysis. Results Univariate analysis showed that DML was longer and compound muscle action potential amplitude of the median nerve, recorded from the abductor pollicis brevis muscle, was smaller in vineyard workers than in the other CTS patients. These differences remained significant after adjusting the results for confounding factors. Conclusions The vineyard workers showed a different pattern of CTS than the other patients: thenar motor fibres were more affected, presumably due to chronic compression on the thenar branch. This suggests an association between “common” CTS and thenar mononeuropathy. Significance Occupational physiologists should clarify the mechanisms of neuromuscular engagement in particular jobs and ergonomists design suitable working tools, because many “individual” risk factors are difficult to change, but workplace-related risk factors can be modified.

Alterations in BRCA1 and BRCA2 genes account for a large proportion of hereditary breast and ovarian cancers. Mutations and variants of unknown pathological significance have been identified in both genes; however, most of them have been studied only at the genomic level, and their effect on mRNA expression remains unknown. We identified two BRCA1 and six BRCA2 splice site variants, and one BRCA2 alteration at exon 14. Our aim was to ascertain the effect on RNA processing of the variants still unclassified. We found that BRCA1 c.IVS11 + 1G>A, BRCA2 c.7252_7272delinsTG, BRCA2 c.IVS2 + 1G>A, BRCA2 c.IVS13-2A>G, BRCA2 c.IVS21 + 4A>G, and BRCA2 c.9345G>A lead to aberrant transcripts in lymphocytes. Five of these six splice site variants caused a complete inactivation of the mutant allele because they produced frameshift similar to previously described deleterious exonic variants. Therefore, we consider them to be true deleterious mutations, possibly associated with an increased lifetime risk of breast or ovarian cancer. BRCA1 c.IVS17 + 6C>G, BRCA2 c.IVS12-9del4, and BRCA2 IVS1-9del3 represent rare variants, not disrupting normal mRNA processing. The last two BRCA2 genetic variants had not been reported in the Breast Cancer Information Core BIC database.

TGF-beta proteins are main regulators of blood vessel development and maintenance. Here, we report an unprecedented link between TGF-beta signaling and arterial hypertension based on the analysis of mice mutant for Emilin1, a cysteine-rich secreted glycoprotein expressed in the vascular tree. Emilin1 knockout animals display increased blood pressure, increased peripheral vascular resistance, and reduced vessel size. Mechanistically, we found that Emilin1 inhibits TGF-beta signaling by binding specifically to the proTGF-beta precursor and preventing its maturation by furin convertases in the extracellular space. In support of these findings, genetic inactivation of Emilin1 causes increased TGF-beta signaling in the vascular wall. Strikingly, high blood pressure observed in Emilin1 mutants is rescued to normal levels upon inactivation of a single TGF-beta1 allele. This study highlights the importance of modulation of TGF-beta availability in the pathogenesis of hypertension.

To analyze the relationship between pain and presence, site, and type of adhesions in women with endometriosis.This was a multicenter, observational cross-sectional study. Eligible for the study were women with endometriosis and pelvic pain, consecutively observed during the study period at the collaborating centers. A total of 574 women entered the study.Adhesions were observed in 81.9% of cases (470 women). The frequency was lower in women with endometriosis at stage I-II (65%) and higher in women with stage III-IV (88%); this difference was statistically significant (p.01). The frequency of adhesions was lower in women with ovarian endometriosis (74%) and higher in those with ovarian and peritoneal endometriosis (87%) or other sites (96%) (p.01). The presence of adhesions was associated with higher mean visual analog scale (VAS) scores and median multidimensional scale ratings in women with ovarian disease and with stage I-II disease. Women with ovarian adhesions reported higher VAS and multidimensional scale scores (p.05) than women with peritoneal adhesions or adhesions in other sites.The results of this study suggest that there is no overall association between the presence of adhesions and the degree of pain in women with endometriosis. The data suggests that there may be an association between adhesions and pain in women with ovarian and Type I-II endometriosis. However, these associations were no longer significant after correction for multiple comparisons. Further research is indicated to test these associations.

Background Germline mutations in the E-cadherin gene (CDH1) are found in up to 48% of families with hereditary diffuse gastric cancer (HDGC), a syndrome characterized by multiple cases of DGC in a family. In 2010, experts updated CDH1 testing criteria and included individuals and families with diagnoses of both DGC and lobular breast cancer (LBC), as an excess of LBC had been observed in HDGC families. We describe the characteristics associated with CDH1 mutations in a group of French patients and show that individuals or families with multiple LBC but no DGC should be offered genetic testing. Methods We studied all index cases in which a CDH1 mutation had been identified between 2006 and 2011 in the Paris region. Results We found 17 index cases with a CDH1 mutation, ten males and seven females, age was 17–63. Eight had familial DGC, four had sporadic DGC at a young age, one was a healthy male with two relatives with DGC, and one was a female with LBC and two siblings with DGC. Additionally, three females (18%) with no personal or family history of DGC had suffered from bilateral LBC under age 50. Only one was tested at diagnosis. She was offered prophylactic gastrectomy, and foci of DGC were seen on the surgical specimen. She is now doing well. The two others, who had initial negative BRCA1/2 screening, were only tested for CDH1 mutations years later after they had developed symptomatic DGC. Discussion Three of our cases were females with bilateral LBC but no personal or family history of DGC. Two of them were only tested for CDH1 mutations once they had developed symptomatic DGC. Prophylactic gastrectomy is now systematically offered to mutation carriers, and these two cases would have been spared highly-lethal, symptomatic DGC, had they benefited from preventive surgery. The 2010 CDH1 testing criteria should be expanded and include cases or families with multiple LBC but no DGC. More precisely, any patient or family with multiple LBC under age 50 should be tested for CDH1 mutations, as carriers are offered life-saving surgery and adapted breast surveillance. Finally, we propose for consideration the name “hereditary diffuse gastric and lobular breast cancer” to define the cancer susceptibility syndrome associated with mutations in CDH1. Disclosure All authors have declared no conflicts of interest.

Background Genetic testing for BRCA1/2 mutations may be useful for prevention and close surveillance as well for treatments selection in cancer patients. Methods Between May 2001 and July 2011 we identified 206 BRCA1/2 mutations carriers: 145 (70%) affected and 61 (30%) unaffected. Of the 145 patients 87 (60%) were found to carry a BRCA1 mutation and 58 (40%) BRCA2. One hundred-twenty-four patients (85%) were diagnosed with breast cancer (BC) and among them 73 (59%) tested BRCA1-positive and 51 (41%) BRCA2-positive. Bilateral BC was found in 26 (21%) patients (46% BRCA1, 54% BRCA2). Ovarian tumor was identified in 30 (21%) women (83% BRCA1-positive), while 12 (8%) had breast plus ovarian cancer (92% BRCA1-positive). Others tumors (oesophagus, pancreas, thyroid): 3 (2%) patients. Results We obtained clinical and pathological data from 38 BC patients. Median age: 40 years (range 23–65); male/female: 1/37. Histology: ductal carcinoma 32 (84%) patients, lobular 1 (3%) patient, medullary 2 (5%) patients, in situ carcinoma 3 (8%) patients. Most of the patients showed stage I BC (19 patients; 50%), while 3 (8%) showed a metastatic spread at the time of diagnosis. Overall 18 (47%) patients had triple negative breast cancer (TNBC), 18 (47%) had hormonal receptor (HR) positive disease, 1 (3%) HER2-positive/HR-negative cancer and 1 was not evaluable. Interestingly, 20 patients were younger than 40 years and among them 11 (55%) had TNBC (91% BRCA1-carriers). Twenty-six patients received neoadjuvant/adjuvant treatments (11 anthracycline-taxane; 8 anthracycline-based; 5 CMF and 2 docetaxel-cyclophosphamide). Among the 7 patients treated with neoadjuvant chemotherapy 2 pCR (ypT0N0) and 5 PR were reported. pCRs were observed in 1 TN and 1 HR-positive BRCA1-carriers, both treated with anthracycline-taxane. Metachronous BC was found in 6 (16%) patients with a median time to diagnosis of 12 years (range 5-22). Prophylactic mastectomy was performed in 4 (10%) patients while 6 (16%) underwent prophylactic bilateral salpingo-oophorectomy. Conclusions Our data seems consistent with previous literature. Interestingly the majority of younger BC patients showed a BRCA1-TN phenotype. Disclosure All authors have declared no conflicts of interest.