Tremulous spastic ataxia in a patient with a homozygous truncating SYNE1 variant.

We describe a case of severe adult-onset progressive tremulous cerebellar ataxia with pyramidal signs associated with a rare homozygous truncating pathogenic variant in the SYNE1 gene (p.Arg5371*). This contrasts the initial views on SYNE1-related ataxia as a relatively benign, slowly progressive condition, with important implications for clinic-genetic counselling.

No evidence of disease activity is associated with reduced rate of axonal retinal atrophy in MS.

OBJECTIVE: To explore, in a longitudinal study, the usefulness of optical coherence tomography (OCT) in monitoring people with multiple sclerosis (MS) by testing the association between retinal nerve fiber layer (RNFL) thinning and clinical and brain MRI criteria of no evidence of disease activity (NEDA). METHODS: OCT, visual evoked potentials (VEPs), and disability, using the Expanded Disability Status Scale (EDSS), were tested at baseline and after 2 years in 72 patients, 63 with routine yearly brain MRI. RESULTS: Longitudinal mean binocular RNFL thinning, in absence of optic neuritis during follow-up, was correlated with EDSS worsening, also controlling for baseline EDSS, RNFL, disease duration, and MS subtype (Spearman ρ -0.462, p < 0.001; partial correlation coefficient -0.437, p < 0.001). At follow-up, patients classified as NEDA (20; 31.7%) had RNFL loss of -0.93 µm ± 1.35 SD, while patients with active disease had -2.83 µm ± 2 SD thinning (t test; p < 0.001). At logistic regression, mean RNFL reduction correctly classified 76.2% of patients as NEDA at 2 years (R2 0.355; p = 0.003). A cutoff of -1.25 µm RNFL loss classified NEDA status with specificity 81.4% and sensitivity 80% (receiver operating characteristic curve: area under the curve 0.8; p < 0.001). No significant longitudinal correlations were found between changes in RNFL and in VEP latencies or scores. CONCLUSIONS: NEDA is associated with a relatively preserved RNFL over 2 years. A greater neuroretinal loss was detected even in patients with clinical evidence of disease activity independently from changes in brain MRI lesions, prompting further validation of OCT as an additional tool in MS monitoring.

Defining minor symptoms in acute ischemic stroke.

BACKGROUND: Thrombolysis is often withheld from acute ischemic stroke patients presenting with mild symptoms; however, up to 40% of these patients end up with a poor outcome when left untreated. Since there is lack of consensus on the definition of minor symptoms, we aimed at addressing this issue by looking for features that would better predict functional outcomes at 3 months. METHODS: Among all acute ischemic stroke patients admitted to our Stroke Unit (n = 1,229), we selected a cohort of patients who arrived within 24 hours from symptoms onset, with baseline NIHSS ≤6, not treated with thrombolysis (n = 304). Epidemiological data, comorbidities, radiological features and clinical presentation (NIHSS items) were collected to identify predictors of outcome. Our cohort was tested against minor stroke definitions selected from the literature and a newly proposed one. RESULTS: Three months after stroke onset, 97 patients (31.9%) had mRS ≥ 2. Independent predictors of poor outcome were age (OR 0.97 [95% CI 0.95-9.99]) and baseline NIHSS score (OR 0.79 [95% CI 0.67-0.94]), while cardioembolic aetiology was negatively associated (OR 3.29 [95% CI 1.51-7.14]). Items of NIHSS associated with poor outcome were impairment of right motor arm (OR 0.49 [95% CI 0.27-0.91]) or the involvement of any of the motor items (OR 0.69 [95% CI 0.48-0.99]). The definition of minor stroke as NIHSS ≤3 and the new proposed definition had the highest sensitivity and accuracy and were independent predictors of outcome. CONCLUSIONS: Our study confirmed that in spite of a low NIHSS score, one third of patients had poor outcome. As already described, age and NIHSS score remained independent predictors of poor outcome even in mild stroke. Also, motor impairment appeared a major determinant of poor outcome. The new proposed definition of minor stroke featured the NIHSS score and the NIHSS items that better predicted functional outcome. Awareness that even minor stroke can yield to poor outcome should sensitize patients to arrive early to the ED and neurologists to administer rt-PA.

Rare case of an adrenocortical neoplasm: A case report and review of literature.

Adrenocortical neoplasms (ACNs) are rare and poorly characterized in infants. The true incidence of ACNs is not well known and it appears to vary substantially across different geographical areas. ACNs are more common in females and two peaks of incidence have been identified: The first year of life and between the age of nine and 16 years. Due to the heterogeneity and rarity of ACNs, their pathological and prognostic classification is challenging. The current study describes the case of a seven-year-old male, who presented to the Department of Pediatric Surgery, University of Siena (Siena, Italy) with a feminization syndrome and increased somatic growth that was associated with a unilateral adrenal mass, which was diagnosed by magnetic resonance imaging. Surgical excision of the mass was performed and histological analysis determined that it was an ACN, with a low risk of malignity; however, the pathological classification of the tumor was challenging. At present, the future behavior of ACNs is unpredictable. Therefore, increasing the knowledge surrounding this type of tumor may aid in its diagnosis, treatment and prognosis. Due to the rarity of pediatric ACNs, no single pediatric oncology center has acquired extensive experience treating this type of tumor. Thus, the initiation of an international tumor registry may aid with the management of patients presenting with ACNs.

Optical coherence tomography and visual evoked potentials: which is more sensitive in multiple sclerosis?

OBJECTIVE: To assess the sensitivity of optic coherence tomography (OCT) and visual evoked potentials (VEPs) to visual pathway abnormalities in multiple sclerosis (MS). METHODS: A total of 40 MS subjects, 28 with optic neuritis (ON) at least 3 months before (bilateral in 5), underwent assessment of visual acuity, Expanded Disability Status Scale (EDSS), OCT and VEPs, the latter quantified with a 0-4 conventional score. RESULTS: OCT and VEPs were abnormal in 36% and 56% respectively in all eyes (p=0.11), 68% and 86% in eyes with previous ON (p=0.12), and in 19% versus 40% in eyes without ON history (p=0.007). Combining VEP and OCT increased sensitivity to 89% in ON and 44% in non-ON eyes. Considering all eyes, global retinal nerve fibre layer (RNFL) thickness and VEP score were significantly correlated between them (ρ=-0.63, p<0.001) and with EDSS (RNFL: ρ=0.40, p<0.001; VEP score: ρ=0.47, p<0.001). Disease duration correlated with VEP score (ρ=0.25, p=0.025) and RNFL thickness (ρ=-0.71, p<0.001). CONCLUSIONS: In eyes without ON, VEPs were more frequently abnormal than OCT, while the two techniques showed similar sensitivity in eyes previously affected by ON. The correlation of VEPs and OCT measures with disability prompts further exploration of the two techniques as potential markers of disease burden.

Deep repetitive transcranial magnetic stimulation with H-coil on lower limb motor function in chronic stroke: a pilot study.

OBJECTIVES: To assess the efficacy of high-frequency (20 Hz) brain stimulation on lower limb motor function in subjects with chronic (> 6 mo) subcortical stroke. DESIGN: Double-blind, placebo-controlled crossover study. SETTING: University hospital. PARTICIPANTS: Right-handed subjects (N=10) affected by a first-ever subcortical stroke in the territory of the middle cerebral artery were included in this study. INTERVENTIONS: Repetitive transcranial magnetic stimulation (rTMS) was delivered with the H-coil, specifically designed to target deeper and larger brains regions. Each subject received both real and sham rTMS in a random sequence. The 2 rTMS cycles (real or sham) were composed of 11 sessions each, administered over 3 weeks and separated by a 4-week washout period. MAIN OUTCOME MEASURES: Lower limb functions were assessed by the lower limb Fugl-Meyer scale, the 10-m walk test, and the 6-minute walk test before and 1 day after the end of each treatment period, as well as at a 4-week follow-up. RESULTS: Real rTMS treatment was associated with a significant improvement in lower limb motor function. This effect persisted over time (follow-up) and was significantly greater than that observed with sham stimulation. A significant increase in walking speed was also found after real rTMS, but this effect did not reach statistical significance in comparison with the sham stimulation. CONCLUSIONS: These data demonstrated that 3 weeks of high-frequency deep rTMS could induce long-term improvements in lower limb functions in the chronic poststroke period, lasting at least 1 month after the end of the treatment.

Thoracoscopic thymectomy in children: our preliminary experience.

INTRODUCTION: The aim of this study is to present a preliminary series of six children affected by an anterior mediastinal mass, resulting in a thymoma. We treated this pediatric population by a video-assisted thoracoscopic thymectomy. PATIENTS AND METHODS: We performed a retrospective study from January 2000 to January 2012 of all children affected by an anterior mediastinal mass, resulting in a thymoma. Data included sex, age at surgery, clinical and radiological features, surgical procedure, follow-up, and complications. RESULTS: Video-assisted thoracoscopic thymectomy was performed in six children (five boys and one girl). Four patients presented with dyspnea and/or thoracic pain treated with analgesic and corticosteroid therapy without any benefits. Two patients were asymptomatic. Preoperatively, exams included radiological imaging, blood, and immunological test. All 6 patients were treated with a thoracoscopic approach; of these patients, 5 were treated with a thoracoscopic right-side thymectomy and 1 with a left-side approach. Patients were treated by a three-trocar technique, and thymectomy was performed using Valleylab (now Covidien) (Boulder, CO) LigaSure™. The mean operative time was 120 minutes. The mean hospital stay was 5 days. In all cases histological findings revealed no malignancy. The mean follow-up was 38 months. DISCUSSION: Thoracoscopic thymectomy facilitated the goal of early thymectomy. The right-side approach is preferred because it gains a good visualization of the venous anatomy for dissection. The left side allows a good extended resection of both the thymus and perithymic fat. Thoracoscopic thymectomy should be consider a valid, less invasive alternative to the most radical open approach.

Ambiguous external genitalia due to defect of 5-α-reductase in seven Iraqi patients: prevalence of a novel mutation.

We report on seven Iraqi patients with 46,XY karyotype and ambiguous genitalia characterized by perineo-scrotal hypospadias, bifid scrotum, clitoris like phallus, palpable testes in inguinal canal and pseudovagina. Patients were raised five as females and two as males. They are all unrelated with the exception of two couples of brothers. The diagnosis of 5-α-reductase-2 deficiency syndrome was first hypothesized on clinical grounds and then confirmed by molecular analysis. Direct sequencing analysis of the SRD5A2 gene revealed in five patients a novel homozygous frame-shift mutation (c.453delC) and in two related patients a previous reported missense mutation. The presence of the same mutation in unrelated patients of the same population suggests a possible founder effect. This report brings the 5-α-reductase-2 deficiency syndrome to the attention of clinical geneticists and child surgeons and discusses the appropriate clinical and surgical strategies for treating these patients.

Juvenile granulosa cell tumor of the testis: prenatal diagnosis and prescrotal approach.

Neonatal testicular tumors are rare and should be considered in the differential diagnosis of newborn scrotal masses. Juvenile granulosa cell tumor (JGCT) accounts for about 5% of all prepubertal testis tumors. As a benign neoplasm, radical orchiectomy is sufficient for treatment. We report a case of a newborn with a prenatal diagnosis of scrotal mass. After surgery, the histological diagnosis was juvenile granulosa cell tumor. To date the patient is healthy.

Littre's hernia in newborn infants: report of two cases.

Littre's hernia was originally defined by Reinke in 1841 as "the presence of a Meckel's diverticulum in any hernial sac." It is generally difficult to differentiate from other types of hernia until complications arise. It is a rare and accidental finding at any age, but it is absolutely exceptional in neonates. To our knowledge, only one case under the age of 1 month has been reported in the literature. Herein two cases treated in the first 20 days of life are reported.

Abnormal oral mucosal light reflectance in infantile hypertrophic pyloric stenosis.

OBJECTIVES: Infantile hypertrophic pyloric stenosis (IHPS) is the most common condition requiring surgical intervention during the first weeks of life. The etiology of IHPS is unknown, although both neuronal nitric oxide synthase upregulation and an extracellular matrix abnormality are suspected. Familial predisposition is an important feature. Phenotypical markers of IHPS, such as hypoplasia or agenesis of the inferior labial frenulum, have been described. The authors tested the hypothesis that IHPS is associated with abnormal reflectance of the oral mucosa. METHODS: Twenty-five children with surgically confirmed IHPS and 25 gender- and age-matched control subjects participated in the study. Reflectance of the lower gingival and vestibular oral mucosa in the optical spectrum was measured using an imaging spectrophotometer. RESULTS: Patients with IHPS had significantly higher light reflectance values in the violet, blue, blue-green, green, yellow, and orange sections of the spectrum (all P values < 0.0001), with a maximum distance between group means at the 450-nm wavelength (t-value: 27.66, df = 48). A reflectance cutoff >5.26% at the 450-nm wavelength identified patients with IHPS with 100% sensitivity and 100% specificity. CONCLUSIONS: This study reports a previously unrecognized mucosal reflectance abnormality of the oral mucosa in IHPS, thus offering a new, accurate, and noninvasive phenotypic marker for the condition.

Polyhydramnios: a predictor of severe growth impairment in achondroplasia.

The phenotypical characteristics in 20 children with achondroplasia were examined in relation to the occurrence of polyhydramnios. A history of polyhydramnios (9 of 20 cases) was associated with a lower height (SD) (P <.05), more severe shortening of the lower segment and upper limbs (P =.0001), and higher frequency of left-handedness (P =.0081).

Neonatal intestinal occlusion due to duodenal duplication in association with malformed gallbladder sludge.

Duodenal duplications are rare observations which can be diagnosed during early pregnancy via US scan. In the neonate they are often cause for intestinal occlusions. Surgical treatment can be limited by the duplication's anatomical interrelationships with adjacent organs. Biliary sludge is an uncommon finding in the first year of life, and can readily regress spontaneously. The association between duodenal duplication and sludge has never been described in the literature in the neonatal period. Here, for the first time, we report on the case of a newborn infant with cystic duplication of the duodenum associated with sludge in a misshapen gallbladder.