Novel mutations in the fukutin gene in a boy with asymptomatic hyperCKemia

Mutations in the fukutin gene were first identified in Japanese patients with classic Fukuyama congenital muscular dystrophy, a severe form of congenital muscular dystrophy associated with cobblestone lissencephaly and ocular defects. Patients of different ethnicities and with milder phenotypes, including limb girdle muscular dystrophy and cardiomyopathy without brain impairment, have also been reported. The hallmark of this disorder, regardless of the clinical outcome, is moderate-to-severe hypoglycosylation of alpha-dystroglycan in muscle sections. We describe the case of a boy harboring two novel mutations in fukutin gene and presenting a five-year history of asymptomatic hyperCKemia, without overt muscle, brain or ocular involvement. Genetic investigations, guided by the presence of moderate myopathic changes on muscle biopsy with loss of immunodetectable alpha-dystroglycan, led to a definitive diagnosis. Cardiac and echocardiographic examinations at follow-up disclosed low normal left ventricular function but no active cardiovascular symptoms. We suggest that fukutin mutations should be sought in asymptomatic hyperCKemia and subclinical heart dysfunction.     

Allogeneic hematopoietic stem cell transplantation for neuromyelitis optica

Neuromyelitis optica is a rare neurological autoimmune disorder characterized by a poor prognosis. Immunosuppression can halt disease progression, but some patients are refractory to multiple treatments, experiencing frequent relapses with accumulating disability. Here we report on durable clinical remissions after allogeneic hematopoietic stem cell transplantation in 2 patients suffering from severe forms of the disease. Immunological data evidenced disappearance of the pathogenic antibodies and regeneration of a naive immune system of donor origin. These findings correlated with evident clinical and radiological improvement in both patients, warranting extended clinical trials to investigate this promising therapeutic option. ANN NEUROL 2014;75:447–453     

Physiological unloading of cardiopulmonary mechanoreceptors by posture changes does not influence the pressor response to isometric exercise in healthy humans

Summary In recent studies in humans the role of cardiopulmonary baroreflexes in modulating the cardiovascular responses to isometric exercise (somatic pressor reflex) has been investigated by performing static hand-grip exercise during deactivation of cardiopulmonary receptors produced by low levels of lower body negative pressure; however, findings from these studies have not been consistent. The purpose of this study was to investigate whether a more physiological unloading stimulus of cardiopulmonary baroreceptors, obtained by sequentially changing posture, could influence the pressor response to somatic afferent stimulation induced by isometric, exercise. To accomplish this, ten healthy subjects performed a 2-min isometric handgrip (IHG) at 30% maximal voluntary contraction after 10 min of supine rest and, in rapid sequence, after 10 min of sitting and 10 min of standing, at the time when, owing to their transitory nature, the cardiovascular effects, due to arterial baroreceptor intervention should have been minimal. During IHG arterial pressure (BP_a) was continuously and noninvasively measured to quantify accurately the blood pressure response to IHG both in magnitude and time course. Results showed that the pressor response to IHG was not significantly influenced by change in posture, either in magnitude or in time course. The mean arterial pressure increased by 17.4 (SEM 2.5), 18.6 (SEM 1.2) and 17.0 (SEM 1.3) mmHg in supine, sitting and standing [2.3 (SEM 0.3), 2.5 (SEM 0.2) and 2.3 (SEM 0.2) kPa] positions, respectively. Also the heart rate response to IHG was unaffected by change in posture. Most important, the sum of the separate BP_a responses induced by supine IHG and by posture change from supine to sitting (summation of reflexes) was not significantly different from the pressor response observed during sitting IHG (interaction of reflexes). Likewise, the sum of the separate BP_a. responses induced by sitting IHG and by changing postures from sitting to standing was not significantly different from the pressor response to standing IHG. These data indicate that, under physiological conditions, cardiopulmonary baroreflexes do not exert a significant role in modulating the reflex pressor drive from muscles during isometric exercise in healthy humans.     

Evaluation of contrast‐enhanced digital mammography (CEDM) in the preoperative staging of breast cancer: Large‐scale single‐center experience

One of the most important indications for contrast‐enhanced breast imaging is the presurgical breast cancer (BC) staging. This is a large‐scale single‐center experience which evaluates the role of CEDM in presurgical staging and its impact on surgical planning. The aims of this retrospective study were to define the diagnostic performance of CEDM in the presurgical setting and to identify which types of patients could benefit from having CEDM. We selected 326 patients with BC who underwent CEDM as preoperative staging and had breast cancer‐related surgery at our institution. We analyzed those cases in which CEDM led to additional imaging or biopsy and those in which it changed the type of surgery that was planned according to conventional breast imaging (CI) techniques (digital mammography, tomosynthesis and bilateral handheld ultrasound). CEDM sensitivity in identifying the index lesion and sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy in the correct preoperative staging of BC of the whole population and in various subgroups were calculated. CEDM sensitivity for the index lesion was 98.8% (322/326), which led to additional breast imaging in 23.6% (77/326) of patients and additional biopsies in 17.5% (57/326). CEDM changed the type of surgery in 18.4% (60/326). In the preoperative breast cancer staging, CEDM sensitivity, specificity, PPV, NPV, and accuracy produced results of 93%, 98%, 90%, 98%, and 97%, respectively. CEDM performance was better in patients with palpable lesions. CEDM has an excellent diagnostic performance in the presurgical staging of BC. Symptomatic patients with palpable lesions benefitted most from preoperative CEDM, with a statistically significant difference compared with nonpalpable.     

Breast cancer in the elderly: treatment of 1500 patients

There is a significant difference in the extent of treatment offered to the elderly with breast cancer; in the United States, while 98% of patients less than 65 years of age receive standard treatment, 81% of those older than 65 years were treated according to protocol. This study's goal was to evaluate disease-specific survival and local-regional recurrence in breast cancer patients more than 65 years of age at diagnosis. A total of 1500 patients with invasive breast carcinoma were treated consecutively from May 1971 to July 2002 at the University of Florence, Florence, Italy. All patients were more than 65 years of age. The median age was 70.6 years (range 65.1-87.3 years).The median follow-up was 8.7 years (range 1-30 years). The crude probability of survival (or relapse occurrence) was estimated using the Kaplan-Meier method and survival (or relapse occurrence) comparisons were carried out using Cox proportional hazard regression models. The Cox regression model by stepwise selection showed as independent prognostic factors for disease-specific survival (DSS), the occurrence of a local relapse (p < 0.0001), pN status (p < 0.0001), the type of surgery (p < 0.0001), and the use of radiotherapy (p < 0.0006) and chemotherapy (p = 0.01). For local disease-free survival (LDFS), the Cox regression model by stepwise selection showed that mastectomy (p < 0.0001), histotype (p < 0.0001), pN status (p < 0.0001), and pT status (p = 0.001) were the only independent prognostic factors. Age was not a prognostic factor for DSS nor LDFS. We suggest treating patients with appropriate treatment for their prognostic factors.     

Molecular markers in laryngeal squamous cell carcinoma: towards an integrated clinicobiological approach

Of the most frequent malignancies in the United States, cancers of the larynx and of the uterine corpus are the only ones not to show an increase in 5-year survival rates over the last 30 years. The increasing use of chemo- and radiotherapy and conservative surgery to preserve organs and their functions has probably led to a better quality of life in patients with laryngeal cancer, but has definitely failed to improve survival, which remains the primary aim. In our opinion, to reduce laryngeal cancer-related mortality, a change in clinical approach is required. We have reviewed the literature on the potential role of molecular markers in the clinical management of laryngeal cancer. We believe that some of the most significant biological markers might be integrated with the evaluation of behavioural risk factors, clinical TNM staging and histopathological grading for a novel clinicomolecular approach to laryngeal cancer. We foresee the use of the most promising biological markers in the phases of prevention, diagnosis, prognostic assessment and drug design.     

Ictal video-polysomnography and EEG spectral analysis in a child with severe Panayiotopoulos syndrome.

OBJECTIVE: To describe the ictal polysomnographic features of a patient with Panayiotopoulos syndrome, a peculiar epileptic syndrome characterized by infrequent, often single, prolonged, nocturnal, focal seizures comprising an unusual constellation of autonomic symptoms (malaise, nausea, pallor, tachycardia, vomiting) and unilateral deviation of the eyes at the onset of seizures. These clinical, ictal manifestations are rarely followed by post-ictal headache. In the literature, there is little information on the ictal EEG characteristics of Panayiotopoulos syndrome and, in particular, on certain autonomic manifestations, such as tachycardia, as the sole ictal phenomena at the onset of seizures. METHODS AND RESULTS: One, all-night videopolysomnography, during which one seizure was recorded. Video-EEG data were evaluated visually and by means of quantitative spectral analysis. The spectral analysis of the recorded seizure showed a complex ictal pattern of cortical involvement with focal onset in the right occipital area followed by the recruitment of widespread extra-occipital cortical regions. CONCLUSIONS: This is the first such analysis of this peculiar epileptic condition. Most of the symptoms were consistent with a diagnosis of severe Panayiotopoulos syndrome, although the patient also presented "atypical findings": a relatively high frequency of seizures, post-ictal headache, no spontaneous remission of seizures with age, and late onset of visual hallucinations; this last finding is more frequent in "Gastaut-type childhood occipital epilepsy", in which onset typically occurs later than in Panayiotopoulos syndrome. [Published with video sequences].