Hypomimia in Parkinson's disease: an axial sign responsive to levodopa.

BACKGROUND AND PURPOSE: Hypomimia is a prominent clinical feature in people with Parkinson's disease (PD), but it remains under-investigated. We aimed to examine the clinical correlates of hypomimia in PD and to determine whether this is a levodopa-responsive sign. METHODS: We included 89 people with PD. Hypomimia was assessed from digital video recordings by movement disorder specialists. Clinical evaluation included use of the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), and assessment of motor and non-motor symptoms using standardized clinical scales. The relationships between hypomimia and other clinical data were analysed using Mann-Whitney U-tests and regression analysis. RESULTS: Hypomimia occurred in up to 70% of patients with PD. Patients with hypomimia had worse UPDRS-III 'off-medication' scores, mainly driven by bradykinesia and rigidity subscores. Patients with hypomimia also had worse apathy than patients without hypomimia. Finally, we found that hypomimia was levodopa-responsive and its improvement mirrored the change by levodopa in axial motor symptoms. CONCLUSION: Our study provides novel information regarding the clinical correlates of hypomimia in people with PD. A better understanding of hypomimia may be relevant for improving treatment and quality of life in PD.

Hymenoptera Venom Allergy: Management of Children and Adults in Clinical Practice.

Hymenoptera venom allergy is an epidemiologically underestimated condition and a major cause of morbidity worldwide. Preventing future allergic reactions in patients who experience a systemic reaction is based on the correct management of the emergency followed by an accurate diagnosis, prescription of adrenaline autoinjectors, and, where indicated, specific venom immunotherapy. Some epidemiological studies highlight our poor knowledge of this disease and the frequent inadequacy of its management. Moreover, they emphasize the importance of such a life-saving treatment as specific immunotherapy. The availability of high-quality hymenoptera venom extracts for diagnostic and therapeutic use has dramatically improved the prognosis and quality of life of allergic patients. Subcutaneous venom immunotherapy is currently the most effective form of allergen-based immunotherapy, with a carry-over effect lasting up to several years after its interruption. This report on the management of hymenoptera venom-allergic children and adults was prepared by a panel of Italian experts. The main objective of this consensus document is to review the scientific evidence related to diagnosis, therapy, and management of patients allergic to hymenoptera venom. Thus, we can improve our knowledge of the disease and promote good clinical practices. The present document provides practical suggestions for correct diagnosis, prescription of emergency therapy and immunotherapy, and strategies for patient care.

Medical management of acute non-specific low back pain: comparison of different medical treatments, one center's retrospective analysis.

Within the developed countries, low back pain and related ailments represent one of the most relevant conditions, affecting both health and socio-economic systems. Non-specific acute low back pain (nsALBP) could represent either an isolated event or the presenting symptom of an underlying condition. Its management is usually medical and radiological investigations should be avoided. However, a general agreement on the best pharmacological treatment is still missing. In the present study, we retrospectively collected patients' data from the institutional database. Two different medical treatments were recognized and groups consequently set. Outcomes were the clinical status, measured using the visual analogue scale (VAS) score for back pain, the use rate of rescue drugs, side effects related to medical treatment, compliance to the treatment, and global satisfaction. The pharma blending of Tramadol 75 mg and Dexketoprofen 25 mg (available blended in a single tablet), resulted effective in the nsALBP management, with less side effects and rescue-drug use along with a higher compliance. Furthermore, patient satisfaction in this treatment group was significatively higher. Many different medical treatments have been investigated and reported in nsALBP management during the last decades. Associations of different drugs are the most common protocols, even though there is no general agreement. Tramadol and Dexketoprofen provide a good clinical result, fewer side effects and a long-lasting and more effective painkiller action, reducing the use of rescue drugs. Moreover, our results suggest that a single tab may provide a higher compliance rate.

Randomised feasibility study of physiotherapy for patients with functional motor symptoms.

OBJECTIVE: To determine the feasibility of conducting a randomised controlled trial of a specialist physiotherapy intervention for functional motor symptoms (FMS). METHODS: A randomised feasibility study was conducted recruiting patients with a clinically established diagnosis of FMS from a tertiary neurology clinic in London, UK. Participants were randomised to the intervention or a treatment as usual control. Measures of feasibility and clinical outcome were collected and assessed at 6 months. RESULTS: 60 individuals were recruited over a 9-month period. Three withdrew, leaving 29 intervention and 28 controls participants in the final analysis. 32% of patients with FMS met the inclusion criteria, of which 90% enrolled. Acceptability of the intervention was high and there were no adverse events. At 6 months, 72% of the intervention group rated their symptoms as improved, compared to 18% in the control group. There was a moderate to large treatment effect across a range of outcomes, including three of eight Short Form 36 (SF36) domains (d=0.46-0.79). The SF36 Physical function was found to be a suitable primary outcome measure for a future trial; adjusted mean difference 19.8 (95% CI 10.2 to 29.5). The additional quality adjusted life years (QALY) with intervention was 0.08 (95% CI 0.03 to 0.13), the mean incremental cost per QALY gained was £12 087. CONCLUSIONS: This feasibility study demonstrated high rates of recruitment, retention and acceptability. Clinical effect size was moderate to large with high probability of being cost-effective. A randomised controlled trial is needed. TRIAL REGISTRATION NUMBER: NCT02275000; Results.

Genetic variation of a global germplasm collection of chickpea (Cicer arietinum L.) including Italian accessions at risk of genetic erosion.

Chickpea (Cicer arietinum L.) is one of the most important legumes worldwide. We addressed this study to the genetic characterization of a germplasm collection from main chickpea growing countries. Several Italian traditional landraces at risk of genetic erosion were included in the analysis. Twenty-two simple sequence repeat (SSR) markers, widely used to explore genetic variation in plants, were selected and yielded 218 different alleles. Structure analysis and hierarchical clustering indicated that a model with three distinct subpopulations best fits the data. The composition of two subpopulations, named K1 and K2, broadly reflects the commercial classification of chickpea in the two types desi and kabuli, respectively. The third subpopulation (K3) is composed by both desi and kabuli genotypes. Italian accessions group both in K2 and K3. Interestingly, this study highlights genetic distance between desi genotypes cultivated in Asia and Ethiopia, which respectively represent the chickpea primary and the secondary centres of diversity. Moreover, European desi are closer to the Ethiopian gene pool. Overall, this study will be of importance for chickpea conservation genetics and breeding, which is limited by the poor characterization of germplasm collection.

A positive diagnosis of functional (psychogenic) tics.

BACKGROUND AND PURPOSE: Functional tics, also called psychogenic tics or pseudo-tics, are difficult to diagnose because of the lack of diagnostic criteria and their clinical similarities to organic tics. The aim of the present study was to report a case series of patients with documented functional tics and to describe their clinical characteristics, risk factors and psychiatric comorbidity. Also clinical tips are suggested which might help the differential diagnosis in clinical practice. METHODS AND RESULTS: Eleven patients (mean age at onset 37.2, SD 13.5; three females) were included with a documented or clinically established diagnosis of functional tics, according to consultant neurologists who have specific expertise in functional movement disorders or in tic disorders. Adult onset, absent family history of tics, inability to suppress the movements, lack of premonitory sensations, absence of pali-, echo- and copro-phenomena, presence of blocking tics, the lack of the typical rostrocaudal tic distribution and the coexistence of other functional movement disorders were common in our patients. CONCLUSIONS: Our data suggest that functional tics can be differentiated from organic tics on clinical grounds, although it is also accepted that this distinction can be difficult in certain cases. Clinical clues from history and examination described here might help to identify patients with functional tics.

Probiotic supplementation in systemic nickel allergy syndrome patients: study of its effects on lactic acid bacteria population and on clinical symptoms.

AIMS: The study aimed to evaluate the effects of probiotic Lactobacillus reuteri DSM 17938 strain supplementation in patients suffering from systemic nickel allergy syndrome, in terms of modulation of faecal LAB population linked to a reduction of GI and cutaneous symptoms and to an increase of patient's quality of life. METHODS AND RESULTS: A preliminary double-blind randomized placebo-controlled study was planned and a culture-independent method based on denaturing gradient gel electrophoresis (DGGE) analysis coupled to the 16S rRNA gene sequencing was applied to investigate on the dynamics of faecal LAB communities before and during a low-Ni diet, supplemented with the probiotic strain. Moreover, the severity and the frequency of GI and cutaneous reactions as well as patient's clinical condition perception (VAS scores) were estimated by statistical analysis. PCR-DGGE fingerprinting obtained using LAB-specific primers revealed significant shift in faecal community with an increase in biodiversity in patients supplemented with probiotic Lact. reuteri strain. In addition, GI reactions such as symptoms related to meals and type of stools significantly improved only in patients treated with Lact. reuteri, while severity and frequency of cutaneous symptoms (urticaria, itch and eczema) and recurrent abdominal pain (RAP) as well as VAS scores statistically decreased in both groups. CONCLUSIONS: Our preliminary findings suggest that probiotic Lact. reuteri could be a useful supplementation during a low-Ni diet of patients with SNAS, to increase LAB population diversity, which could contribute to restore the intestinal homoeostasis conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: To date, no information is available on probiotics application and on their effects, in terms of intestinal microbiota modulation, on patients suffering from SNAS. Therefore, the identification of dominant LAB community and the study of its shift during the probiotic supplementation could enhance the knowledge of the SNAS syndrome.

Systemic nickel allergy syndrome: epidemiological data from four Italian allergy units.

The prevalence of nickel hyper-sensitivity varies widely in different countries, nevertheless it is the leading cause of contact dermatitis. The presence of nickel in the diet (mainly plant foods) in some nickel-sensitive subjects can provoke/aggravate eczema and systemic contact dermatitis as well as cause extra-cutaneous symptoms (respiratory, gastrointestinal, neurological). These symptoms, correlated to the ingestion of nickel-containing foods and beverages, in nickel patch test positive individuals, defines the so called Systemic Nickel Allergy Syndrome (SNAS), a condition successfully treated by oral desensitization. Although numerous studies have investigated the prevalence of contact nickel allergy or addressed the relationship between nickel intake and onset of systemic symptoms, to our knowledge no epidemiological studies have attempted to estimate the prevalence of SNAS. Therefore, we decided to evaluate consecutive patients (1,696), afferent to four allergy units in Sicily, a region of southern Italy, from October 2010 to March 2011. SNAS was confirmed in 98 patients (5.78 percent) of the 1,696 studied, suggesting that this clinical entity may be an emergent allergological condition rather than an occasional finding. The most common symptoms complained of in our population were cutaneous (51 patients), gastrointestinal (87 patients) and other systemic clinical manifestations (37 patients). Furthermore, 16 out of the 98 SNAS patients (16.3 percent) presented IgE-mediated food allergy with a statistically significant association (X2=16.950; P<0.0001), therefore suggesting underlying cross-facilitating pathways. These findings need confirmation on wider populations but may help allergists to suspect, during common clinical practice, that cutaneous and extra-cutaneous symptoms may be referred to nickel intake and deserve specific in-depth investigation.

The management of severe hypoglycemia by the emergency system: the HYPOTHESIS study.

BACKGROUND AND AIMS: Severe hypoglycemia is not rare in diabetes and markedly impacts on health resource use. We aimed to describe the characteristics of patients attending emergency departments (EDs) following a severe episode of hypoglycemia, the factors associated with the management of events and the final outcome. METHODS AND RESULTS: We carried out a retrospective analysis of cases attending 46 Italian EDs for hypoglycemia from January 2011 to June 2012. A total of 3753 records were retrieved from the databases of the participating centers, part of a network repeatedly involved in collaborative studies; 3516 episodes occurred in subjects with diabetes (median age, 76 years; range, 1-102). Comorbidities were recorded in 2320 (65.9%) diabetes cases; association with trauma or road accidents in 287 (8.2%) and 47 (1.3%), respectively. Patients were treated with insulin (49.8%), oral agents (31.4%), or combination treatment (15.1%). The event required assistance by the out-of-hospital Emergency services in 1821 cases (51.8%). Following the ED visit, admission to hospital departments was deemed necessary in 1161 cases (33.1%). Diabetes treatment (oral agents: OR, 1.63; 95% confidence interval (CI), 1.37-1.94), increasing age (OR, 1.39; 95% CI, 1.31-1.48) and the number of comorbidities (OR, 1.51; 95% CI, 1.38-1.66) were the main drivers of admission. The in-hospital death rate was 10%, associated with the number of comorbidities (OR, 1.28; 95%CI, 1.01-1.63). CONCLUSION: Severe hypoglycemia requiring referral to EDs is associated with a significant work-up of the Emergency services and a remarkable in-hospital death rate in frail individuals with diabetes.

Systemic nickel allergy: oral desensitization and possible role of cytokines interleukins 2 and 10.

Nickel ingested with food can elicit either systemic cutaneous or gastrointestinal symptoms causing a systemic nickel allergy syndrome (SNAS) that can be treated with tolerance by oral ingestion of the metal. It has been suggested that interleukins 2 (IL-2) and 10 (IL-10) are involved in the mechanisms underlying oral tolerance. We evaluated the clinical efficacy of oral desensitization therapy in SNAS consisting in the administration of nickel sulphate. Because nickel allergy prevalently affects women, only female subjects (N = 22) were recruited. Oral nickel desensitizing therapy was associated with low-nickel diet for three months. Before and after therapy, clinical conditions were evaluated, and circulating cytokines IL-2 and IL-10 were measured. After the two-year treatment, visual analogue scale (VAS) scores for symptoms were significantly reduced (P less than 0.001). Patients were released by either cutaneous or gastrointestinal symptoms and by tolerating nickel-containing food. At the end of the treatment, nickel oral challenge test was negative in 18 patients, and IL-2 level in the serum was significantly reduced while IL-10 was increased, although this datum was not statistically significant. Our study confirms the clinical efficacy of nickel oral immunotherapy and focuses on the mechanisms triggered by oral tolerance indicating that reduction of IL-2 can be associated with success of oral nickel desensitizing therapy.

The dynamic sagittal balance: Definition of dynamic spino-pelvic parameters using a method based on gait analysis.

Introduction: Evaluation of sagittal balance parameters is a standard assessment before spine surgery. However, these parameters can change during walking. We aimed to describe the behavior of spino-pelvic parameters during walking in healthy subjects. Material and methods: Analyses were performed in 60 healthy subjects. Static spinal sagittal balance parameters were assessed. We performed gait analysis and we used SMART-DX 500® to analyze parameters aimed at defining dynamic sagittal balance, including pelvic tilt angle (PTA), sagittal trunk shift (STS), and trunk angle (TA). We considered rotational and obliquity movements of the pelvis, flexo-extension movements of the hip, trunk, and knees. Analyses were performed in a standing posture and during walking. Results: PTA-cycle, PTA-stance, PTA-swing, STS-cycle, STS-stance, and STS-swing showed good-to-excellent internal reliability (ICC = 0.867; ICC = 0.700; ICC = 0.817, respectively). The parameters with the lowest variability were radiographic PI (CV = 16.53%), PTA-stance (CV = 9.55%), and PTA-swing (CV = 17.22%). PT was directly related to PTA-cycle (r = 0.534, p = .027). PI was inversely correlated with trunk flexo-extension range of motion (r = -0.654, p = .004) and dynamic PT (r = -0.489, p = .047). LL and SS were directly related to knee flexo-extension (r = 0.505, p = .039; r = 0.493, p = .045, respectively). SVA was correlated with the trunk obliquity in dynamics (r = 0.529, p = .029). PTA-cycle was directly related to trunk obliquity (r = 0.538, p = .049). STS and TA in the three phases of step were related to the kinematic parameters of the pelvis. TA was related to flexo-extension of the hip and knee. Conclusions: Variations of dynamic spino-pelvic parameters occur during walking and modify sagittal balance from a static to a dynamic condition.

Cefixime-induced nonconvulsive status epilepticus.

Nonconvulsive status epilepticus (NCSE) is an epileptic condition lasting >30 min, clinically manifested by an altered mental state and associated with continuous epileptiform activity on the electroencephalogram. NCSE is a common yet still under recognized condition and delay in diagnosis and treatment may be associated with increased mortality as well as cognitive/behavioral consequences. We described an epileptic female patient assuming carbamazepine (900 mg/day) and levetiracetam (3,000 mg/day), seizure free for more than 10 years, who developed NCSE during cefixime treatment, a third-generation cephalosporin compound that along with penicillins is classified within the b-lactam class of antibiotics. In our report we outline the importance and the difficulty to choose secure antibiotic treatment in epileptic patients, we discuss the possible mechanisms by which cephalosporins induce neurotoxicity and the need to stress family components questioning about new drugs assumed. Finally we highlight the value of the EEG recording to diagnose NCSE and treat it adequately and promptly.

Intrajejunal levodopa infusion in advanced Parkinson's disease: long-term effects on motor and non-motor symptoms and impact on patient's and caregiver's quality of life.

BACKGROUND: Continuous infusion of intrajejunal levodopa/carbidopa gel (CIILG) for advanced Parkinson's disease (PD) has been proved to be beneficial on motor complications, non-motor symptoms and quality of life in the short-term follow-up. Aim of this two-center, retrospective, open-label study was to evaluate the long-term effect of CIILG on patients' condition and caregivers' quality of life. MATERIALS AND METHODS: The assessments (performed at baseline and at latest follow-up available after CIILG) included: the unified PD rating scale (UPDRS I-IV), the non-motor symptoms scale (NMSS), the PD questionnaire (PDQ-8), the PD sleep scale (PDSS), and a battery assessing the cognitive and psychiatric status as well as caregiver's quality of life. Medications were expressed as levodopa equivalent daily dose (LEDD). RESULTS: 14 advanced PD patients (age: 67.0 +/- 11.5 years, disease duration: 12.9 +/- 4.8 years) were followed for 24.9 +/- 14.4 months after CIILG. Total LEDD was unchanged at follow-up, however therapy was globally simplified by reducing dopamine agonists (DAs). A statistically significant beneficial effect was shown on motor complications while the severity of motor symptoms did not change over time. A significant improvement of depressive symptoms and psychiatric side effects caused by DAs was detected. Sleep quality and diurnal somnolence ameliorated as revealed by the significant reduction of PDDS. Caregivers' stress and patients' quality of life were not significantly improved. However, when categorized according to their outcome, patients with improvement of motor condition and functionality gained an improvement of quality of life. Apart from the severity of motor impairment at baseline, no other predicting factors were detected. CONCLUSIONS: CIILG is an effective treatment option for patients with advanced PD over the long-term period as it may improve both the motor complications and the psychiatric side effects caused by other dopaminergic therapies.

The adhesion molecule ICAM-1 is overexpressed in patients with Hymenoptera venom allergy and decreases after ultrarush venom immunotherapy.

Adhesion molecules, including ICAM-1, are an important factor in allergic inflammation caused by inhalant allergens, but there are no studies investigating their possible role in Hymenoptera venom allergy (HVA). We measured the level of ICAM-1 in 13 venom-allergic patients before and after ultra-rush venom immunotherapy (VIT). Eight patients were treated by yellow jacket venom and 5 were treated by honeybee venom. Serum ICAM-1 levels were assayed by an immunoenzymatic method, with a detection limit of 0.35 ng/ml. The mean level of ICAM-1 changed from 316.4±78.2 ng/ml before VIT to 294.7±77.9 after VIT. This difference was statistically significant (p = 0.019). These findings show that in patients with HVA there is an over-expression of ICAM-1, and that ultra-rush VIT significantly decreases ICAM-1 levels. It is likely that the known ability of VIT to correct the imbalance in T lymphocytes subpopulations and in the associated production of cytokines may account for this observation. In fact, such cytokines include IL-4 and TNF-alpha, that up-regulate adhesion molecules.

Endovascular Treatment of Ruptured Intracranial Blister Aneurysms: A Systematic Review and Meta-analysis.

BACKGROUND: Endovascular treatment of blister aneurysms is a promising approach, even though they are vascular lesions challenging to treat due to their angioarchitectural characteristics. PURPOSE: Our aim was to investigate clinical and radiologic outcomes after endovascular treatment of ruptured blister aneurysms. DATA SOURCES: PubMed, Ovid MEDLINE, Ovid EMBASE, Scopus, and the Web of Science were screened. STUDY SELECTION: We performed a comprehensive review of the literature from 2010 to 2019 reporting series of patients with blister aneurysms treated with an endovascular approach. DATA ANALYSIS: Event rates were pooled across studies using a random effects meta-analysis. DATA SYNTHESIS: A total of 32 studies reporting on 684 patients (707 aneurysms) were included. Stent placement, stent-assisted coiling, and flow diversion were the most commonly described treatments (282, 256, and 155 patients, respectively). The long-term complete occlusion rate was 76.9% (95% CI, 69.2%-83.9%). The perioperative complication rate was 8.9%, and clinical outcome at final follow-up was mRS <2 in 76.6% (95% CI, 68.2%-84.2%) of patients. The mortality rate was 4.7% (95% CI, 2.30%-7.80%). Among the different techniques, stent-assisted coiling is the one that had the higher rate of immediate occlusion (63.4%); however, the occlusion rate at the final follow-up was comparable among the different techniques. LIMITATIONS: Different techniques were described and data were reported in a nonhomogeneous way, possibly representing a bias in the present study. CONCLUSIONS: This study suggests that endovascular treatment of blister aneurysms is associated with good long-term occlusion rates and reasonable complication and mortality rates. There is no consensus on the best endovascular techniques in blister aneurysm management.

On a stochastic leaky integrate-and-fire neuronal model.

The leaky integrate-and-fire neuronal model proposed in Stevens and Zador (1998), in which time constant and resting potential are postulated to be time dependent, is revisited within a stochastic framework in which the membrane potential is mathematically described as a gauss-diffusion process. The first-passage-time probability density, miming in such a context the firing probability density, is evaluated by either the Volterra integral equation of Buonocore, Nobile, and Ricciardi ( 1987 ) or, when possible, by the asymptotics of Giorno, Nobile, and Ricciardi (1990). The model examined here represents an extension of the classic leaky integrate-and-fire one based on the Ornstein-Uhlenbeck process in that it is in principle compatible with the inclusion of some other physiological characteristics such as relative refractoriness. It also allows finer tuning possibilities in view of its accounting for certain qualitative as well as quantitative features, such as the behavior of the time course of the membrane potential prior to firings and the computation of experimentally measurable statistical descriptors of the firing time: mean, median, coefficient of variation, and skewness. Finally, implementations of this model are provided in connection with certain experimental evidence discussed in the literature.

Mutation of a bHLH transcription factor allowed almond domestication.

Wild almond species accumulate the bitter and toxic cyanogenic diglucoside amygdalin. Almond domestication was enabled by the selection of genotypes harboring sweet kernels. We report the completion of the almond reference genome. Map-based cloning using an F1 population segregating for kernel taste led to the identification of a 46-kilobase gene cluster encoding five basic helix-loop-helix transcription factors, bHLH1 to bHLH5. Functional characterization demonstrated that bHLH2 controls transcription of the P450 monooxygenase-encoding genes PdCYP79D16 and PdCYP71AN24, which are involved in the amygdalin biosynthetic pathway. A nonsynonymous point mutation (Leu to Phe) in the dimerization domain of bHLH2 prevents transcription of the two cytochrome P450 genes, resulting in the sweet kernel trait.