[Prospective randomized controlled trial on 2 940 nm fractional erbium laser combined with fractional micro-plasma radiofrequency in the treatment of facial atrophic acne scars].

Objective: To compare the efficacy and safety of 2 940 nm fractional erbium laser combined with fractional micro-plasma radiofrequency (FMR) therapy and 2 940 nm fractional erbium laser in the treatment of atrophic acne scars. Methods: A prospective randomized controlled research was conducted. A total of 100 atrophic acne scar patients (38 males and 62 females, aged 18-37 years) who were treated in the Scar Laser Clinic of the Department of Plastic and Reconstructive Surgery of Shanghai Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine from March 2018 to March 2021 and conformed to the inclusion criteria were recruited. The patients were randomly divided into erbium laser+FMR group and erbium laser alone group, with 50 cases in each group. The facial acne scars of patients in erbium laser alone group were treated with 2 940 nm fractional erbium laser, while the facial acne scars of patients in erbium laser+FMR group were treated with erbium laser as above, besides, the scars of U and M types were treated with FMR, once every 3 months for a total of 3 times. Before the first treatment and 3 months after each treatment, the Echelle D'Assessment Clinique des Cicatrices D'Acne (ECCA) was used to score the scar. The occurrence of adverse reaction during the treatment process was observed and recorded, and the incidence was calculated. Three months after the last treatment, the 5-level classification method was used to evaluate the satisfaction of patients with the treatment effect, and the satisfaction rate was calculated. Data were statistically analyzed with independent sample t test and chi-square test. Results: A total of 89 patients completed the study, including 46 patients in erbium laser+FMR group (19 males and 27 females, aged (26±5) years) and 43 patients in erbium laser alone group (15 males and 28 females, aged (27±6) years). The ECCA scores before the first treatment and 3 months after the first treatment of patients were similar between the two groups (P>0.05). The ECCA scores of patients in erbium laser+FMR group at 3 months after the second and third treatment were 72±23 and 61±18, respectively, which were significantly lower than 85±26 and 76±25 in erbium laser alone group (with t values of -2.45 and -3.26, respectively, P<0.05). During the treatment process, the incidence of adverse reaction of patients in erbium laser+FMR group and erbium laser alone group were 23.91% (11/46) and 16.28% (7/43), respectively, and there was no statistically significant difference between the two groups (P>0.05). The satisfaction rate of patients in erbium laser+FMR group was 78.26% (36/46) at 3 months after the last treatment, which was significantly higher than 53.49% (23/43) in erbium laser alone group (χ2=6.10, P<0.05). Conclusions: The 2 940 nm fractional erbium laser combined with FMR is superior to 2 940 nm fractional erbium laser alone in the treatment of facial atrophic acne scars, achieving significantly higher efficacy without significantly increasing the incidence of adverse reaction, and patients are more satisfied with the efficacy. It can be used as a recommended therapy in clinical practice.

Atypical chorioretinal lesions in Siberian Husky dogs with primary angle-closure glaucoma: a case series.

BACKGROUND: A number of etiologies for different canine chorioretinal lesions have been proved or suggested but some fundic lesions remain unclear in terms of an etiologic diagnosis, treatment options and prognosis. The purpose of this case series is to describe atypical chorioretinal lesions observed in dogs with primary angle-closure glaucoma (PACG). CASE PRESENTATION: Two spayed-female Siberian Huskies (3- and 4-year-old) and one Siberian Husky/Australian Shepherd mixed breed dog (11-month-old) that had multifocal depigmented retinal lesions and PACG were included. PROCEDURES: Ophthalmic examination, gross, and histopathologic examination findings are described. One of the dogs underwent further clinical diagnostics. Advanced clinical diagnostics on the fellow, presumed to be non-glaucomatous eye of a dog revealed: pectinate ligament dysplasia by gonioscopy, retinal thinning in the depigmented area and wedge shaped retinal thinning with delayed choroidal vascular perfusion by optical coherence tomography, confocal scanning laser ophthalmoscopy, fluorescein and indocyanine green angiography. Quantifiable maze testing for the same eye revealed mild nyctalopia but the full-field electroretinogram showed no generalized decrease of retinal function. Genetic testing for mutations within the retinitis pigmentosa GTPase regulator gene causing X-linked progressive retinal atrophy in Siberian Huskies was negative. Histopathologic evaluations on enucleated eyes in two dogs confirmed goniodysgenesis, PACG with optic nerve head cupping, and diffuse inner retinal atrophy. In addition, segmental profound retinal atrophy, loss of retinal pigment epithelium, and adhesion of the retina to Bruch's membrane was observed and coincided with multifocal depigmented lesions noted on fundic examination. CONCLUSIONS: To our knowledge, this is the first case series with clinical and histopathologic data of chorioretinal lesions, most likely caused by severely impaired choroidal perfusion. Further studies are warranted to elucidate the etiology and pathophysiology, including its possible association with PACG.

Lifestyle and dietary factors associated with serologically detected gastric atrophy in a Caucasian population in the GISTAR study.

OBJECTIVE: To identify dietary and lifestyle factors associated with decreased pepsinogen levels indicative of gastric atrophy. METHODS: Participants aged 40 to 64 from the "Multicentric randomized study of H. pylori eradication and pepsinogen testing for prevention of gastric cancer mortality (GISTAR study)" in Latvia tested for serum pepsinogen, as well as for Helicobacter pylori infection by 13 C-urea breath test or serology were included. Data on sex, age, education, employment, diet, smoking, alcohol and proton pump inhibitor use were obtained by survey and compared for participants with and without serologically detected gastric atrophy defined as pepsinogen I/pepsinogen II ≤ 2 and pepsinogen I ≤ 30 ng/mL. RESULTS: Of 3001 participants (median age 53, interquartile range, 11.0, 36.9% male) 52.8% had H. pylori and 7.7% had serologically detected gastric atrophy. In multivariate analysis, increasing age, consumption of alcohol, coffee, and onions were positively, while H. pylori , former smoking, pickled product and proton pump inhibitor use were inversely associated with gastric atrophy. Pepsinogen values were higher in smokers and those with H. pylori . Pepsinogen ratio was lower in those with H. pylori . When stratifying by H. pylori presence, significantly higher pepsinogen levels remained for smokers without H. pylori . CONCLUSION: Several dietary factors and smoking were associated with serologically detected gastric atrophy. Pepsinogen levels differed by smoking and H. pylori status, which may affect the serologic detection of gastric atrophy. There seems to be a complicated interaction between multiple factors. A prospective study including atrophy determined by both serology and histology is necessary.

Factors influencing thigh muscle volume change with cycling exercises in acute spinal cord injury - a secondary analysis of a randomized controlled trial.

Objective: To conduct a per-protocol analysis on thigh muscle volume outcomes from the Spinal Cord Injury and Physical Activity (SCIPA) Switch-On Trial.Design: Secondary analysis from an assessor-blind randomized, controlled trial.Setting: Four acute/sub-acute hospitals in Australia and New Zealand.Participants: 24 adults (1 female) within four weeks of motor complete or incomplete spinal cord injury (SCI)Intervention: Functional electrical stimulation-assisted cycling (FESC) or passive cycling (PC) 4x/week for 12 weeks.Outcome Measures: Whole thigh and muscle group volumes calculated from manually segmented MR images.Results: 19/24 participants completed ≥ twelve weeks of the intervention. Five participants experienced hypertrophy (4 FESC; 1 PC) and eight attenuation of atrophy (<20% volume loss) (3 FESC; 5 PC) in thigh muscle volume. Six participants were non-responders, exhibiting atrophy >20% (3 FESC; 3 PC). Mean (SD) change for FESC was -2.3% (25.3%) and PC was -14.0% (12.3%). After controlling for baseline muscle volumes, a strong significant correlation was found between mean weekly exercise frequency and quadriceps and hamstring volumes (r=6.25, P=0.006), regardless of mode. Average watts was highly correlated to quadriceps volumes only (r=5.92, P=0.01), while total number of sessions was strongly correlated with hamstring volumes only (r=5.91, P=0.01).Conclusion: This per-protocol analysis of FESC and PC early after SCI reports a partial response in 42% and a beneficial response in 25% of patients who completed 12 weeks intervention, regardless of mode. Strong correlations show a dose-response according to exercise frequency. Characteristics of non-responders are discussed to inform clinical decision-making.

Reduced Thalamic Volume and Metabolites in Type 1 Diabetes with Polyneuropathy.

OBJECTIVE: Thalamus is essential in processing of sensory information. This study explored the associations between thalamic volume and intra-thalamic metabolites and associations to clinical and experimental characteristics of sensory function in adults with diabetic polyneuropathy. METHODS: 48 adults with type 1 diabetes and confirmed distal symmetric peripheral neuropathy (DPSN) and 28 healthy controls participated in a cross-sectional study and underwent a brain magnetic resonance imaging scan. Estimates for thalamic volume were extracted using voxel-based morphometry and intra-thalamic N-acetylaspartate/creatine (NAA/cre) levels were assessed by magnetic resonance spectroscopy. Associations between thalamic volume and clinical measures, quantitative sensory testing and neuropathic phenotype were explored. RESULTS: In diabetes, reduced gray matter volume was identified including bilateral thalamus (all p≤0.001) in comparison to healthy participants. Thalamic volume estimates were positively associated to intra-thalamic NAA/cre (r=0.4; p=0.006), however not to diabetes duration (p=0.5), severity of DSPN (p=0.7), or presence of pain (p=0.3). Individuals with the lowest thalamic volume had greatest loss of protective sensation (light touch using von Frey-like filaments, p=0.037) and highest pain tolerance to electric stimulation (tetanic stimulation, p=0.008) compared to individuals with the highest thalamic volume. CONCLUSIONS: In this cohort with type 1 diabetes and severe DSPN, thalamic atrophy was present and associated with reduced NAA/cre, indicating thalamic structural loss and dysfunction. Thalamic atrophy was associated to reduced sensory function involving large fiber neuropathy and sensation to tetanic stimulation that may reflect synaptic transmission. This may ultimately contribute to the current understanding of the pathophysiology behind the perception changes evident in DSPN.

Baseline folic acid status affects the effectiveness of folic acid supplements in cognitively relevant outcomes in older adults: a systematic review.

BACKGROUND: Folic acid was investigated for decreased concentrations of the same type of cysteine (Hcy), which is considered a risk factor for Alzheimer's disease. However, the conclusions are inconsistent, while supplementing elders with different folic acid states. METHOD: The PubMed, Science Network and EMBASE databases were searched for randomized controlled trials published over the past decade; The 11/485 study was included on the basis of pre-defined criteria. Cognitive-related results, including cognitive function and brain atrophy, were measured using cognitive scales and magnetic resonance imaging. RESULTS: Significant cognitive benefits were reported in individuals with incomplete folic acid (n s 4); However, individuals with sufficient folic acid (n s 2) do not benefit from supplements, evaluated by the cognitive scale. On the other hand, a significant positive association was established in the participants of plasma Hcy, but the folic acid state was sufficient (n s 2). One study reported that folic acid supplements did not provide any benefit, but folic acid status data were missing. In addition, folic acid supplementation also improves brain atrophy (n s 2). CONCLUSION: Baseline folic acid status may be a potential factor affecting the results of cognitive function folic acid supplementation in older adults. Older people with insufficient folic acid will benefit from folic acid supplementation.

Distinct Patterns of Brain Atrophy associated with Mild Behavioral Impairment in Cognitively Normal Elderly Adults.

A cross-sectional study was conducted to evaluate patterns of gray matter changes in cognitively normal elderly adults with mild behavioral impairment (MBI). Sixteen MBI patients and 18 healthy controls were selected. All the participants underwent a neuropsychological assessment battery, including the Mini-mental State Examination (MMSE), Geriatric Depression Scale (GDS), Self-rating Anxiety Scale (SAS), and Chinese version of the mild behavioral impairment-checklist scale (MBI-C), and magnetic resonance imaging (MRI) scans. Imaging data was analyzed based on voxel-based morphometry (VBM). There was no significant difference in age, gender, MMSE score, total intracranial volume, white matter hyperdensity, gray matter volume, white matter volume between the two groups (p > 0.05). MBI group had shorter education years and higher MBI-C score, GDS and SAS scores than the normal control group (p < 0.05). For neuroimaging analysis, compared to the normal control group, the MBI group showed decreased volume in the left brainstem, right temporal transverse gyrus, left superior temporal gyrus, left inferior temporal gyrus, left middle temporal gyrus, right occipital pole, right thalamus, left precentral gyrus and left middle frontal gyrus(uncorrected p < 0.001). The grey matter regions correlated with the MBI-C score included the left postcentral gyrus, right exterior cerebellum, and left superior frontal gyrus. This suggests a link between MBI and decreased grey matter volume in cognitively normal elderly adults. Atrophy in the left frontal cortex and right thalamus in MBI patients is in line with frontal-subcortical circuit deficits, which have been linked to neuropsychiatric symptoms (NPS) in dementia. These initial results imply that MBI might be an early harbinger for subsequent cognitive decline and dementia.

Antisense Oligonucleotide Reverses Leukodystrophy in Canavan Disease Mice.

Marked elevation in the brain concentration of N-acetyl-L-aspartate (NAA) is a characteristic feature of Canavan disease, a vacuolar leukodystrophy resulting from deficiency of the oligodendroglial NAA-cleaving enzyme aspartoacylase. We now demonstrate that inhibiting NAA synthesis by intracisternal administration of a locked nucleic acid antisense oligonucleotide to young-adult aspartoacylase-deficient mice reverses their pre-existing ataxia and diminishes cerebellar and thalamic vacuolation and Purkinje cell dendritic atrophy. Ann Neurol 2020;87:480-485.

Evaluation of Biological Effects of Hydroalcoholic Extract of Hibiscus Rosa Sinensis Flowers on Alloxan Induced Diabetes in Rats.

Aim and Objective The current study sought to investigate antidiabetic, hypolipidimic, antioxidant and histopathological effects of floral extract of Hibiscus rosa sinensis in Alloxan induced Diabetes in rats. Materials and Methods Study was conducted on 6 groups with 6 wistar rats in each group for the period of 4 weeks. Group I: served as normal control (NC), rats administered with gum acacia 1 ml daily, group II: consider as diabetic control (DC) treated with alloxon 150 mg/kg body wt. Whereas Hibiscus rosa-sinensis flower extract was given orally in group III (DE1), group IV (DE2), group V (DE3) at doses of 50, 100 and 200 mg/kg body weight dissolved in distilled water respectively. Group VI (DG) was given glibenclamide (5 mg/kg) as a standard drug and results were compared in reference to it. Results The results indicate that the test compound HEFHR (Hydroalcoholic extract of flower Hibiscus rosa-sinensis) has significant and sustained oral antidiabetic activity, comparable with the hypoglycemic effect of Glibenclamide and Sulphonylurea. Flower extract of HRS was more efficacious in lipid lowering effect and in antioxidative activity than glibenclamide. After 28 day treatment with flower extract, size of islets was significantly increased and necrosis and atrophy of islets were significantly improved; also increase in number and diameter of cell islets appeared to be regular as compared to the diabetic group. Conclusion HEFHR possesses significant antidiabetic, hypolipidemic and antioxidant properties as well as regeneration of beta cells in rats. Further evaluation of HEFHR is in progress.

High versus moderate energy use of bipolar fractional radiofrequency in the treatment of acne scars: a split-face double-blinded randomized control trial pilot study.

Bipolar fractional radiofrequency (FRF) device was firstly FDA-approved for treating atrophic acne scar in 2008 through the process of dermal coagulation and minimal epidermal ablation. The average energy at 60 mJ/pin was widely used to treat atrophic acne scars. However, the higher energy was delivered, the deeper ablation and coagulation were found. At present, the new generation of a device with bipolar FRF technology with electrode-pin tip was developed to maximize ability to deliver energy up to 100 mJ/pin. The objective of the study was to explore and compare the efficacy of utilizing high energy (100 mJ/pin) and moderate energy (60 mJ/pin) of bipolar fractional radiofrequency in treatment of atrophic acne scar in Asians. This is a split-face, double-blinded, randomized control trial, pilot study by using parallel group design technique. Thirty healthy subjects with Fitzpatrick skin phototype III-IV diagnosed as atrophic acne scares were enrolled. All subjects received four monthly sessions of bipolar FRF treatment. Left and right facial sides of individual patients were randomly assigned for different energy (high energy at 100 mJ/pin versus moderate energy at 60 mJ/pin). Acne scars improvement was blinded graded by dermatologist using global acne scarring score (GASS) which was subjectively evaluated at baseline, 1-, 3-, and 6-month follow-up. Objective scar analysis was also done using UVA-light video camera to measure scar volume, skin smoothness, and wrinkle at baseline, 3-, and 6-month follow-up after the last treatment. Side effects including pain, erythema, swelling, and crusting were also recorded. Thirty subjects completed the study with full 4-treatment course. The mean GASS of high energy side and moderate energy side was significantly reduced at 1-, 3-, and 6-month follow-up visits. At 1 month follow-visit, high energy side demonstrated significant improvement compared with moderate energy side (p = 0.03). Postinflammatory hyperpigmentation (PIH) developed in 21/120 sessions in high energy side (17.5 %) and 16/120 sessions in moderate energy side (13.3 %). Pain score and the duration of erythema after treatments were significant higher on the side that was treated with high energy. Bipolar FRF device was safe and effective in the treatment of atrophic acne scars in Asians. High energy setting demonstrated significant higher efficacy at 1 month follow-visit. However, the efficacy of both energy settings was comparable at 3- and 6-month follow-up. In addition, side effects were significantly more intense on the side treated with high energy.

Influence of treatment of vulvovaginal atrophy with intravaginal prasterone on the male partner.

OBJECTIVE: The aim was to analyze the opinion of the male partner of women treated for vulvovaginal atrophy (VVA) with intravaginal 0.50% DHEA (prasterone), thus providing information on both members of the couple. METHODS: On a voluntary basis, in a prospective, randomized, double-blind and placebo-controlled phase-III clinical trial, the male partner filled a questionnaire at baseline and at 12 weeks stating his observations related to his penis and intercourse before and after VVA treatment. RESULTS: Sixty-six men having a partner treated with intravaginal DHEA and 34 others having a partner treated with placebo answered the questionnaires. Concerning the feeling of vaginal dryness of their female partner, the severity score following DHEA treatment improved by 81% (0.76 units) over placebo (p = 0.0347). Thirty-six percent of men having a partner treated with DHEA did not feel the vaginal dryness of the partner at the end of treatment compared to 7.8% in the placebo group. When analyzing the situation at 12 weeks compared to baseline, an improved score of 1.09 units was the difference found for the DHEA group compared to 0.76 for the placebo group (p = 0.05 vs. placebo). In the DHEA group, 38% of men scored very improved compared to 18% in the placebo group. No adverse event has been reported. CONCLUSION: The male partner had a very positive evaluation of the treatment received by his female partner.

Thalamic atrophy predicts cognitive impairment in relapsing remitting multiple sclerosis. Effect on instrumental activities of daily living and employment status.

INTRODUCTION: Cognitive impairment is an important predictor of quality of life at all stages of MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. OBJECTIVE: The aim of the study was to designate the MRI marker that predicts cognitive decline and explore its effect on every day activities and employment status. METHODS: 50 RRMS patients and 31 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Everyday activities were evaluated with the instrumental activities of daily living (IADL) scale and employment status. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, corpus callosum and thalamic atrophy. RESULTS: The frequency of cognitive dysfunction for our RRMS patients was 38%. RRMS patients differed significantly from controls on the TMTA, TMTB, phonological verbal fluency task, memory, psychomotor speed, reaction time and cognitive flexibility. Neuropsychological measures had a strong correlation with all MRI atrophy measures and a weak or moderate correlation with lesion volume. Psychomotor speed was the most sensitive marker for IADL, while memory and TMTB for employment status. Thalamic area was the most sensitive MRI marker for memory, psychomotor speed and TMTB.. CONCLUSION: Thalamic atrophy predicts the clinically meaningful cognitive decline in our RRMS patients.

Decreased efficacy of twice-weekly intravaginal dehydroepiandrosterone on vulvovaginal atrophy.

OBJECTIVE: While daily intravaginal administration of 0.50% (6.5 mg) dehydroepiandrosterone (DHEA, prasterone) for 12 weeks has shown clinically and statistically significant effects on moderate to severe (MS) dyspareunia as the most bothersome symptom (MBS), the present study analyzes the effect of a reduced dosing regimen on MBS vaginal dryness. METHOD: Daily intravaginal 0.50% prasterone for 2 weeks followed by twice weekly for 10 weeks versus placebo. RESULTS: Maximal beneficial changes in vaginal parabasal and superficial cells and pH were observed at 2 weeks as observed for intravaginal 10 µg estradiol (E2). This was followed by a decrease or lack of efficacy improvement after switching to twice-weekly dosing. The decrease in percentage of parabasal cells, increase in percentage of superficial cells and decrease in vaginal pH were all highly significant (p < 0.0001 to 0.0002 over placebo) at 12 weeks. In parallel, the statistical significance over placebo (p value) on MBS vaginal dryness at 6 weeks was 0.09 followed by an increase to 0.198 at 12 weeks. For MBS dyspareunia, the p value of 0.008 at 6 weeks was followed by a p value of 0.077 at 12 weeks, thus illustrating a decrease of efficacy at the lower dosing regimen. The improvements of vaginal secretions, color, epithelial integrity and epithelial surface thickness were observed at a p value < 0.01 or 0.05 over placebo at 2 weeks, with a similar or loss of statistical difference compared to placebo at later time intervals. No significant adverse event was observed. Vaginal discharge related to the melting of Witepsol was reported in 1.8% of subjects. CONCLUSION: The present data show that daily dosing with 0.50% DHEA for 2 weeks followed by twice-weekly dosing is a suboptimal treatment of the symptoms/signs of vulvovaginal atrophy resulting from a substantial loss of the efficacy achieved at daily dosing.

A 12-week treatment with fractional CO2 laser for vulvovaginal atrophy: a pilot study.

OBJECTIVE: This pilot study aimed to assess the efficacy and feasibility of fractional CO2 laser in the treatment of vulvovaginal atrophy (VVA) in postmenopausal women. METHODS: VVA symptoms were assessed before and after three applications of laser over 12 weeks in 50 women (age 59.6 ± 5.8 years) dissatisfied with previous local estrogen therapies. Subjective (visual analog scale) and objective (Vaginal Health Index Score, VHIS) measures were used during the study period to assess VVA. Quality of life was measured by using the SF-12. A subjective scale to evaluate the degree of pain related to the laser application and the degree of difficulty to perform the laser procedure was used. RESULTS: Fractional CO2 laser treatment was effective to improve VVA symptoms (vaginal dryness, vaginal burning, vaginal itching, dyspareunia, dysuria; p < 0.001) at 12-week follow-up, as well as the VHIS (13.1 ± 2.5 at baseline vs. 23.1 ± 1.9; p < 0.001). Both physical and mental scores of quality of life were significantly improved in comparison with baseline (p < 0.001). Satisfaction with the laser procedure was reported by 42 women (84%) and a minimal discomfort was experienced at the first laser application, mainly because of the insertion and the movements of the probe. Finally, the technique was very easy to perform in all women starting from the second application at week 4 and no adverse events were recorded during the study period. CONCLUSIONS: A 12-week treatment with the fractional CO2 laser was feasible and induced a significant improvement of VVA symptoms by ameliorating vaginal health in postmenopausal women. Further controlled studies should be performed to confirm the present data and to assess the long-term effects of the laser procedure on vaginal tissues.

Volumetric analysis of the hypothalamus, amygdala and hippocampus in non-suicidal and suicidal mood disorder patients--a post-mortem study.

In recent years, the hypothalamus, amygdala and hippocampus have attracted increased interest with regard to the effects of stress on neurobiological systems in individuals with depression and suicidal behaviour. A large body of evidence indicates that these subcortical regions are involved in the pathogenetic mechanisms of mood disorders and suicide. The current neuroimaging techniques inadequately resolve the structural components of small and complex brain structures. In previous studies, our group was able to demonstrate a structural and neuronal pathology in mood disorders. However, the impact of suicide remains unclear. In the current study we used volumetric measurements of serial postmortem sections with combined Nissl-myelin staining to investigate the hypothalamus, amygdala and hippocampus in suicide victims with mood disorders (n = 11), non-suicidal mood disorder patients (n = 9) and control subjects (n = 23). Comparisons between the groups by using an ANCOVA showed a significant overall difference for the hypothalamus (p = 0.001) with reduced volumes in non-suicidal patients compared to suicide victims (p = 0.018) and controls (p = 0.006). To our surprise, the volumes between the suicide victims and controls did not differ significantly. For the amygdala and hippocampus no volume changes between the groups could be detected (all p values were n. s.). In conclusion our data suggest a structural hypothalamic pathology in non-suicidal mood disorder patients. The detected differences between suicidal and non-suicidal patients suggest that suicidal performances might be related to the degree of structural deficits.

Distributed, limbic gray matter atrophy in patients after bacterial meningitis.

BACKGROUND AND PURPOSE: The structural basis of cognitive sequelae after bacterial meningitis in humans is still poorly understood. In animal models and human autopsy cases, neuronal apoptosis of the hippocampal formation in particular seems to play an important role. Here, we aimed to analyze if BM entails MR imaging structural consequences in humans in vivo. MATERIALS AND METHODS: We applied voxel-based morphometry in a cohort of BM survivors with normal conventional MR imaging after resolution of the acute inflammation to assess morphologic differences. RESULTS: We found clear gray matter volume loss in the limbic system including the hippocampal formation, thalamus, and cingulate gyri bilaterally as well as in the temporal lobe. These results were corroborated by an alternative atlas-based method. CONCLUSIONS: Even in patients with normal routine MR imaging results, clear-cut gray matter atrophy with a mesial temporal/limbic pattern was evident. The anatomic distribution is compatible with the neuropsychological deficit commonly observed in patients after BM. The similarity of the observed atrophy may point to causal link between BM and mesial temporal epilepsy.

Concomitant fractional anisotropy and volumetric abnormalities in temporal lobe epilepsy: cross-sectional evidence for progressive neurologic injury.

BACKGROUND: In patients with temporal lobe epilepsy and associated hippocampal sclerosis (TLEhs) there are brain abnormalities extending beyond the presumed epileptogenic zone as revealed separately in conventional magnetic resonance imaging (MRI) and MR diffusion tensor imaging (DTI) studies. However, little is known about the relation between macroscopic atrophy (revealed by volumetric MRI) and microstructural degeneration (inferred by DTI). METHODOLOGY/PRINCIPAL FINDINGS: For 62 patients with unilateral TLEhs and 68 healthy controls, we determined volumes and mean fractional anisotropy (FA) of ipsilateral and contralateral brain structures from T1-weighted and DTI data, respectively. We report significant volume atrophy and FA alterations of temporal lobe, subcortical and callosal regions, which were more diffuse and bilateral in patients with left TLEhs relative to right TLEhs. We observed significant relationships between volume loss and mean FA, particularly of the thalamus and putamen bilaterally. When corrected for age, duration of epilepsy was significantly correlated with FA loss of an anatomically plausible route - including ipsilateral parahippocampal gyrus and temporal lobe white matter, the thalamus bilaterally, and posterior regions of the corpus callosum that contain temporal lobe fibres - that may be suggestive of progressive brain degeneration in response to recurrent seizures. CONCLUSIONS/SIGNIFICANCE: Chronic TLEhs is associated with interrelated DTI-derived and volume-derived brain degenerative abnormalities that are influenced by the duration of the disorder and the side of seizure onset. This work confirms previously contradictory findings by employing multi-modal imaging techniques in parallel in a large sample of patients.

Sacral nerve stimulation for fecal incontinence related to external sphincter atrophy.

BACKGROUND: Atrophy of the external anal sphincter, a pathologic muscle volume anomaly associated with fecal incontinence, has been shown to be a negative predictor of the outcome of surgery for defects of the external anal sphincter. It is unclear whether external anal sphincter atrophy also affects the outcome of sacral nerve stimulation for fecal incontinence. OBJECTIVE: Our aim was to assess the effectiveness of sacral nerve stimulation in patients with fecal incontinence and external anal sphincter atrophy and to determine whether severity of atrophy and concomitant presence of a sphincter defect are negative predictors of outcome. DESIGN: This was a prospective observational study of treatment outcome. SETTING: The study was conducted from November 2004 through November 2010 at a regional hospital in Italy. PATIENTS: Consecutive patients with fecal incontinence and external anal sphincter atrophy were included. By means of MRI, patients were determined to have either moderate (<50%) or severe (≥ 50%) thinning of and/or replacement of sphincter muscle by fat. The concomitant presence of defects of the external anal sphincter was also detected by MRI. INTERVENTION: All patients underwent sacral nerve stimulation through a staged implantation procedure. MAIN OUTCOME MEASURES: The main outcome measures were improvement in the Cleveland Clinic Florida Fecal Incontinence Scale (Wexner score), number of episodes of incontinence per week, and the Fecal Incontinence Quality of Life Scale. RESULTS: A total of 28 patients underwent definitive implantation of the sacral nerve stimulation device. Wexner scores decreased from a median of 16 (range, 10-20) at baseline to 3 (range, 0-8) at 6-month follow-up (p < 0.001). Weekly incontinence episodes decreased from a mean (SD) of 14.7 (12.5) to 0.40 (0.82); p < 0.001. Improvement was significantly related to severity of fecal incontinence (r = 0.86; p < 0.001). Overall quality-of-life scores improved from a mean of 1.8 (0.6) to 3.8 (0.4);p < 0.001. Sacral nerve stimulation was effective in both moderate (n = 16) and severe (n = 12) atrophy and in patients with (n = 8) or without (n = 20) external anal sphincter defects. LIMITATIONS: The study was limited by its observational nature and relatively small sample size. CONCLUSIONS: Sacral nerve stimulation can be effective in restoring continence and improving quality of life in patients with fecal incontinence related to atrophy of the external anal sphincter, regardless of the severity of atrophy. Moreover, the presence of EAS atrophy does not influence the success of the outcome of SNS in patients with a sphincter defect. These findings are consistent with the hypothesis that the effects of SNS are not achieved solely by its action on the anal sphincter complex.

Atypical presentation of a novel Presenilin 1 R377W mutation: sporadic, late-onset Alzheimer disease with epilepsy and frontotemporal atrophy.

Mutations within Presenilin 1 (PSEN1) represent the most common cause of monogenic Alzheimer Disease (AD). The clinical phenotype is highly variable, even if early onset disease with an autosomal dominant pattern of inheritance and presenting memory deficits usually occur. In the present work, we described the case of a late-onset AD patient, without any positive family history for dementia, and associated with seizures and behavioural symptoms. Structural and functional neuroimaging showed frontotemporal changes without posterior biparietal brain abnormalities. Cerebrospinal analysis was consistent with AD pattern, with decreased Aß42 and increased Tau and phospho-Tau. A novel pathogenetic mutation within PSEN1 gene was detected within exon 8, leading to a substitution from arginine to tryptophan (AGG > TGG: R377W), affecting a splice junction and protein function. The case herein reported further confirms the heterogeneity of PSEN1 mutations and the need to take into account genetic screening in those cases with atypical presentation.

Pitch discrimination in cerebellar patients: evidence for a sensory deficit.

In the last two decades, a growing body of research showing cerebellar involvement in an increasing number of nonmotor tasks and systems has prompted an expansion of speculations concerning the function of the cerebellum. Here, we tested the predictions of a hypothesis positing cerebellar involvement in sensory data acquisition. Specifically, we examined the effect of global cerebellar degeneration on primary auditory sensory function by means of a pitch discrimination task. The just noticeable difference in pitch between two tones was measured in 15 healthy controls and in 15 high functioning patients afflicted with varying degrees of global cerebellar degeneration caused by hereditary, idiopathic, paraneoplastic, or postinfectious pancerebellitis. Participants also performed an auditory detection task assessing sustained attention, a test of verbal auditory working memory, and an audiometric test. Patient pitch discrimination thresholds were on average five and a half times those of controls and were proportional to the degree of cerebellar ataxia assessed independently. Patients and controls showed normal hearing thresholds and similar performance in control tasks in sustained attention and verbal auditory working memory. These results suggest there is an effect of cerebellar degeneration on primary auditory function. The findings are consistent with other recent demonstrations of cerebellar-related sensory impairments, and with robust cerebellar auditorily evoked activity, confirmed by quantitative meta-analysis, across a range of functional neuroimaging studies dissociated from attention, motor, affective, and cognitive variables. The data are interpreted in the context of a sensory hypothesis of cerebellar function.