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Introduction Intravenous thrombolysis (IT) and mechanical thrombectomy (MT) have significantly changed the clinical outcome of acute ischaemic stroke (AIS). Concerns about possible complications often reduce the use of these treatment options for older patients, preferentially managed with antiplatelet therapy (AT). Aim of this study was to evaluate, in a population of middle-old (75–84 years) and oldest-old (≥ 85 years) subjects, the efficacy and safety of different treatments for AIS (IT, IT + MT, MT or AT), mortality and incidence of serious complications. Patients and methods All patients aged over 75 years admitted for AIS in two Stroke Units were enrolled. The physician in each case considered all treatment options and chose the best approach. NIHSS and modified Rankin Scale (mRS) were obtained and differences between admission and discharge scores, defined as delta(NIHSS) and delta(mRS), were calculated. The relationship between delta(NIHSS), delta(mRS) and type of procedure was analysed with a GLM/Multivariate model. Differences in mortality and incidence of serious complications were analysed with the chi-square test. Results A total of 273 patients, mean age 84.07 (± 5.47) years, were included. The Delta(NIHSS) was significantly lower in patients treated with AT than in those treated with IT and MT (p p p Conclusions Our results suggest that IT and AT are effective and relatively safe approaches in middle-aged and older patients.

Background: Randomized controlled trials (RCTs) proved that short-term (21–90 days) dual antiplatelet therapy (DAPT) reduces the risk of early ischemic recurrences after a noncardioembolic minor stroke or high-risk transient ischemic attack (TIA) without substantially increasing the hemorrhagic risk. We aimed at understanding whether and how real-world use of DAPT differs from RCTs. Methods: READAPT (Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or TIA) is a prospective cohort study including >18-year-old patients treated with DAPT after a noncardioembolic minor ischemic stroke or high-risk TIA from 51 Italian centers. The study comprises a 90-day follow-up from symptom onset. In the present work, we reported descriptive statistics of baseline data of patients recruited up to July 31, 2022, and proportions of patients who would have been excluded from RCTs. We compared categorical data through the χ² test. Results: We evaluated 1070 patients, who had 72 (interquartile range, 62–79) years median age, were mostly Caucasian (1045; 97.7%), and were men (711; 66.4%). Among the 726 (67.9%) patients with ischemic stroke, 226 (31.1%) did not meet the RCT inclusion criteria because of National Institutes of Health Stroke Scale score >3 and 50 (6.9%) because of National Institutes of Health Stroke Scale score >5. Among the 344 (32.1%) patients with TIA, 69 (19.7%) did not meet the RCT criteria because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score 24 hours) DAPT initiation; 776 (72.5%) and 676 (63.2%) patients did not take loading doses of aspirin and clopidogrel, respectively. Overall, 84 (7.8%) patients met the RCT inclusion/exclusion criteria. Conclusions: The real-world use of DAPT is broader than RCTs. Most patients did not meet the RCT criteria because of the severity of ischemic stroke, lower risk of TIA, late DAPT start, or lack of antiplatelet loading dose. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05476081.

Mild cognitive impairment is frequent among people with Parkinson’s disease. Cognitive training seems effective for cognitive status and for mitigating anxiety and depression. With the COVID-19 outbreak, such therapeutic interventions were delivered online. This longitudinal mixed-method study was aimed at evaluating the effectiveness of an online cognitive treatment, carried out during COVID times and based on Parkinson’s-Adapted Cognitive Stimulation Therapy, on cognitive domains and mood of 18 older people with Parkinson’s disease. After screening, the cognitive status and mood were assessed three times by Addenbrooke’s Cognitive Examination-Revised scale and the Geriatric Depression Scale-Short Form. At the follow-up, patients were also interviewed for understanding their experience with the technology. Such treatment was effective on the participants’ cognitive functions, but not on their mood. Despite some initial problems with the technology, the online intervention was experienced as a way of not being ‘left behind’, staying in contact with others, and being safe during the lockdown. This suggests that online cognitive treatment can be adopted to integrate face-to-face interventions by increasing their efficacy, accessibility, and long-term outcomes. Suggestions for future research are given.

(1) Background: Parkinson’s disease (PD) is one of the most frequent causes of disability among older people. Recently, virtual reality and exergaming have been emerged as promising tools for gait and balance rehabilitation in PD patients. Our purpose is to evaluate an innovative treatment for older patients with PD, based on non-immersive virtual reality exergames, improving gait and balance and reducing falling risk. (2) Methods: Thirty PD patients were recruited and randomly divided into two groups, to receive a traditional rehabilitation (CG) or a technological rehabilitation (TG). (3) Results: A statistical improvement of balance at the end of treatments was observed in both groups (CG: 12.4 ± 0.7 vs. 13.5 ± 0.8, p = 0.017; TG: 13.8 ± 0.5 vs. 14.7 ± 0.4, p = 0.004), while the overall risk of falling was significantly reduced only in the TG (POMA Total: 24.6 ± 0.9 vs. 25.9 ± 0.7, p = 0.010). The results between groups shows that all POMA scores differ in a statistically significant manner in the TG, emphasizing improvement not only in balance but also in gait characteristics (9.7 ± 0.8 vs. 11.4 ± 0.2, p = 0.003). Moreover, TG also improves the psychological sphere, measured thorough MSC-(17.1 ± 0.4 vs. 16.5 ± 0.4, p = 0.034). Although an improvement in FES-I and Gait Speed can be observed, this increase does not turn out to be significant. (4) Conclusions: Results suggest how non-immersive virtual reality exergaming technology offers the opportunity to effectively train cognitive and physical domains at the same time.

The aim of this paper is to describe the results collected with the Italian study conducted within eWare project, aimed at supporting the autonomy and health of the older people affected by dementia and their informal caregivers, through the use of an innovative system based on a social robot and a sensorized environmental infrastructure. Nine dyads of older participants with their caregivers were enrolled in testing the system for 6 months. The results show a positive impact of the system in supporting the achievement of personal goals of the participants, as well as in supporting the quality of life of the informal caregivers. Nevertheless, the impact of the system in reducing the caregivers’ burden needs to be deeply investigated. This research highlights the potential of the eWare system but modifications will have to be made, especially on the interactivity capabilities, in order to meet the peculiar needs and wishes of older people with dementia and to favor the long-term use of the system.

This pilot project was aimed at supporting those families caring at home for loved ones suffering from Alzheimer dementia. Fourteen dyads of "caregivers-loved ones with dementia" were recruited and assigned either to the experimental group (n = 7) or to the control group (n = 7). The experimental group attended a training course, an Alzheimer Café, a self-help group for caregivers, and the support from a volunteer and professional nurse in-home visits, while the control group's dyads attended a standard intervention. To investigate the effects of this integrated and interprofessional model of care, caregivers completed the Caregiver Burden Inventory and 2 ad hoc structured questions to evaluate whether quality of life of the dyads was changed. Moreover, the caregivers of the experimental group completed the Self-Assessment Single Questionnaire, version 6 (Q-UAV6). Only caregivers of the experimental group reported a significant reduction in burden and an improved quality of life of the dyad. They also showed a greater acceptance of the disease, became experts in the care of their loved ones, and improved their relationship. The creation of a service integration network of professionals, volunteers, and families has been shown to be useful in supporting those families caring at home for loved ones suffering from Alzheimer dementia.

Background Stroke is a leading cause of disability, injury, and death in elderly people and represents a major public health problem with substantial medical and economic consequences. The incidence of stroke rapidly increases with age, doubling for each decade after age 55 years. Gait impairment is one of the most important problems after stroke, and improving walking function is often a key component of any rehabilitation program. To achieve this goal, a robotic gait trainer seems to be promising. In fact, some studies underline the efficacy of robotic gait training based on end-effector technology, for different diseases, in particular in stroke patients. In this randomized controlled trial, we verify the efficacy of the robotic treatment in terms of improving the gait and reducing the risk of falling and its long-term effects. Methods In this single-blind randomized controlled trial, we will include 152 elderly subacute stroke patients divided in two groups to receive a traditional rehabilitation program or a robotic rehabilitation using G-EO system, an end-effector device for the gait rehabilitation, in addition to the traditional therapy. Twenty treatment sessions will be conducted, divided into 3 training sessions per week, for 7 weeks. The control group will perform traditional therapy sessions lasting 50 min. The technological intervention group, using the G-EO system, will carry out 30 min of traditional therapy and 20 min of treatment with a robotic system. The primary outcome of the study is the evaluation of the falling risk. Secondary outcomes are the assessment of the gait improvements and the fear of falling. Further evaluations, such as length and asymmetry of the step, walking and functional status, and acceptance of the technology, will be carried. Discussion The final goal of the present study is to propose a new approach and an innovative therapeutic plan in the post-stroke rehabilitation, focused on the use of a robotic device, in order to obtain the beneficial effects of this treatment. Trial registration ClinicalTrials.gov NCT04087083. Registered on September 12, 2019

(1) Background: Parkinson’s Disease (PD) is one of the most common causes of disability among older individuals. The advanced stages of PD are usually characterized by postural instability and, as a consequence, falls. Those are among the main factors that determine the quality of life, as well as the morbidity and mortality of a person with PD. In the field of PD rehabilitation, robotics is also rapidly gaining ground. As a primary aim, we evaluate the acceptability of the technology integrated intervention, using the Psychosocial Impact of Assistive Devices Scale (PIADS), in order to analyze the attitude of the participants towards the Tymo® system. As a secondary outcome, we assess the result of the rehabilitation treatment integrated with the Tymo® system on several patient’s features. (2) Methods: We studied a population of 16 patients with Parkinson’s Disease. Each recruited subject completed 10 treatment sessions, organized as two training sessions per week, for 5 weeks. The intervention included 30 min of traditional therapy and 20 min of technological treatment with a robotic system. PIADS is composed of three subscales (Competence subscale, Adaptability subscale, Self-esteem subscale) ranging from −3 to +3, reflecting, respectively, a negative or positive feeling towards the device. (3) Results: The Competence subscale, measuring feelings of competence and usefulness, obtained a score of 1.24 (SD = 0.78). The score of Adaptability subscale, indicating a willingness to try out new things and to take risks, was 1.83 (SD = 0.65). Finally, the Self-esteem subscale, indicating feelings of emotional health and happiness, reached a score of 1.31 (SD = 0.72). Moreover, statistical analysis reveals a significant effect on balance performance after intervention. (4) Conclusions: This feasibility study represents a starting point in the use of technology in the rehabilitation pathway of patients affected by Parkinson’s Disease. In fact, our results suggest that a standard therapy combined with an innovative treatment using Tymo® may be accepted by PD patients, which may benefit especially from preserving balance.

BACKGROUND Dementia is a neurodegenerative syndrome characterized by impaired cognitive functions associated with psychological and behavioral disorders. The informal caregiver has a central role in the life of the person with dementia. Committing a large part of the day to caring for the assisted person inevitably has an effect on the caregiver's life. OBJECTIVE To analyze the impact of a psychosocial intervention dedicated to a group of informal caregivers of patients with Alzheimer’s disease, guided by a trained psychologist for facilitating the expression of emotional state, compared to a traditional self-help group. METHODS The study design is Randomized Controlled Trial, that includes an experimental group, in which the participants will undertake the psychosocial intervention, and a control group, where participants will receive support according to the traditional self-help methodology. Interventions for both groups will last 4 months with 16 sessions. RESULTS We hypothesize that the experimental group is more effective in managing caregiver burden and coping strategies and that this can be more helpful in the perception of well-being, anxiety and depression of the caregiver. CONCLUSIONS Our study aims to compare two types of help: self-mutual help and a psychosocial group with elements of emotional support. This study may also give us more information about the most appropriate ways to support and help caregivers of people with dementia. CLINICALTRIAL The study was approved by the Ethic Committee of the Istituto Nazionale Ricovero e Cura per Anziani (IRCCS INRCA) on the 26th of November 2020.

The identification of diagnostic-prognostic biomarkers of dementia has become a global priority due to the prevalence of neurodegenerative diseases in aging populations. The objective of this study was to assess the diagnostic performance of cerebrospinal fluid (CSF) biomarkers across patients affected by either Alzheimer’s disease (AD), tauopathies other than AD (TP), or vascular dementia (VD), and cognitively normal subjects (CNS). One hundred fifty-three patients were recruited and tested for classical AD CSF biomarkers- Amyloid-ß42 and tau proteins - and novel candidate biomarkers - neurofilament (NF-) light and microRNA (miR) -21, -125b, -146a, and -222. All dementia patients had significantly higher concentrations of NF-light compared to CNS, with the TP group displaying the highest NF-light values. A significant inverse correlation was also observed between NF-light and cognitive impairment. Of the four miRNAs analyzed, miR-222 levels were significantly increased in VD patients compared to both CNS and AD. In addition, while NF-light showed a better diagnostic performance than miR-222 and classical AD biomarkers in differentiating TP and VD from CNS, classical AD biomarkers revealed higher performance in discriminating AD from non-AD disorders. Overall, our results suggest that CSF NF-light and miR-222 are promising biomarkers that may help to diagnose non-AD disorders.

Objectives The purpose of this study was to investigate the prognostic weight of multimorbidity and functional impairment over long-term mortality among older patients discharged from acute care hospitals. Design A prospective multicenter observational study. Setting and Participants Our series consisted of 1967 adults aged ≥65 years consecutively admitted to acute care wards in Italy, in the context of the Report-AGE project. Methods After signing a written informed consent, all patients underwent comprehensive geriatric assessment by Inter-RAI Minimum Data Set acute care. The primary endpoint of the present study was long-term mortality. Patients were grouped into 3 functional clusters and 3 disease clusters using the K-medians cluster analysis. The association of functional clusters, disease clusters, and Charlson score categories with long-term mortality was investigated through Cox regression analysis and the intercluster classification agreement was further estimated. Finally, the additive effect of either disease clusters or Charlson score on predictive ability of functional clusters was assessed by using changes in Harrell’s C-index and categorical Net Reclassification Index (NRI). Results Functional clusters, disease clusters, and Charlson score were significant predictors of long-term mortality, but the interclassification agreement was poor. Functional clusters predicted mortality with greater accuracy [C-index 0.66, 95% confidence interval (CI) 0.65–0.68] compared with disease clusters (C-index 0.54, 95% CI 0.53–0.56), and Charlson score (C-index 0.58, 95% CI 0.56–0.59). Adding multimorbidity (NRI 0.23, 95% CI 0.14–0.31) or Charlson score (NRI 0.13, 95% CI 0.03–0.20) to functional cluster model slightly improved the accuracy of prediction. Conclusions and Implications Functional impairment may better predict prognosis compared with multimorbidity, which may be relevant to optimally address individuals’ needs and to design tailored preventive interventions.

Background: Many studies have underlined as caregiving for people with Alzheimer’s disease (AD) is highly stressful and has significant negative consequences. Objectives: The study of the structure of personality, can help to understand the association between depression, intrapsychic and interpersonal processes of caregivers of Alzheimer’s disease patients and what kind of intervention can be planned to favor the stress burden management. Methods: Case group: Caregivers (CG) (n = 75); control group, Subjects not Caregivers (nCG) (n. 104). Tests: SASB questionnaire (Structural Analysis of Interpersonal Behavior) describing intrapsychic and interpersonal processes of the structure of personality validated on the basis of DSMIV; CDQ questionnaires—depression. Results: Intrapsychic level: From the results it emerged that CGs had lower autonomy in their choices, and lower acceptance of their own feelings, and exercised greater self-control exhausting themselves toward predetermined goals, and more depression compared to the control group. They may be not able to achieve psychic equilibrium in the presence of stress: they may likely become disoriented and engage in behaviors that may be self-defeating. SASB-Cl = Autonomy (p < 0.001); SASB-Cl2-Autonomy and Love (p < 0.001), SASB-CL3-Love (p < 0.001); SASB-Cl4 Love and control (p < 0.001), SASB-CL5-Control (p = 0.015), SASB-Cl6-Control and hate (p < 0.001), SASB-Cl7-Hate (p < 0.001). Conclusions: Intrapsychic characteristics such as tendency to depression, inability to being in contact with their own feelings, excessive self-control may be linked to difficulties in facing burden of care and indicate serious difficulties to adaptation to burden condition. The knowledge of these modalities could allow to plan a psychotherapeutic and multidisciplinary intervention aimed at facing and overcoming the psychological distress of the caregiver.

Supplemental Digital Content is available in the text., Background and Purpose: We aimed to investigate the rate of hospital admissions for cerebrovascular events and of revascularization treatments for acute ischemic stroke in Italy during the coronavirus disease 2019 (COVID-19) outbreak. Methods: The Italian Stroke Organization performed a multicenter study involving 93 Italian Stroke Units. We collected information on hospital admissions for cerebrovascular events from March 1 to March 31, 2020 (study period), and from March 1 to March 31, 2019 (control period). Results: Ischemic strokes decreased from 2399 in 2019 to 1810 in 2020, with a corresponding hospitalization rate ratio (RR) of 0.75 ([95% CI, 0.71–0.80] P

Objective: the objective of this review is to analyze the advances in the field of rehabilitation through virtual reality, while taking into account non-immersive systems, as evidence have them shown to be highly accepted by older people, due to the lowest “cibersikness” symptomatology. Data sources: a systematic review of the literature was conducted in June 2019. The data were collected from Cochrane, Embase, Scopus, and PubMed databases, analyzing manuscripts and articles of the last 10 years. Study selection: we only included randomized controlled trials written in English aimed to study the use of the virtual reality in rehabilitation. We selected 10 studies, which were characterized by clinical heterogeneity. Data extraction: quality evaluation was performed based on the Physioterapy Evidence Database (PEDro) scale, suggested for evidence based review of stroke rehabilitation. Of 10 studies considered, eight were randomized controlled trials and the PEDro score ranged from four to a maximum of nine. Data synthesis: VR (Virtual Reality) creates artificial environments with the possibility of a patient interaction. This kind of experience leads to the development of cognitive and motor abilities, which usually positively affect the emotional state of the patient, increasing collaboration and compliance. Some recent studies have suggested that rehabilitation treatment interventions might be useful and effective in treating motor and cognitive symptoms in different neurological disorders, including traumatic brain injury, multiple sclerosis, and progressive supranuclear palsy. Conclusions: as it is shown by the numerous studies in the field, the application of VR has a positive impact on the rehabilitation of the most predominant geriatric syndromes. The level of realism of the virtual stimuli seems to have a crucial role in the training of cognitive abilities. Future research needs to improve study design by including larger samples, longitudinal designs, long term follow-ups, and different outcome measures, including functional and quality of life indexes, to better evaluate the clinical impact of this promising technology in healthy old subjects and in neurological patients.

Background: Type 2 diabetes (T2D) is correlated to amnestic mild cognitive impairment (aMCI) and to non-amnestic mild cognitive impairment (naMCI). This study evaluated whether the T2D variable characterizes a peculiar cognitive profile in elderly patients. Moreover, it explores the association between glycated hemoglobin levels (HbA1c), T2D duration, insulin and oral hypoglycemic agent treatment, and cognition in elderly diabetic patients. Methods: Detailed neuropsychological battery was used to diagnose MCI subtypes. A total of 39 MCI subjects with T2D (T2D-MCI) and 37 MCI subjects without T2D (ND-MCI), matched for age, educational level, and Mini-Mental State Examination score, were included. Results: ND-MCI performed worse in memory and language domains than T2D-MCI. The amnestic subtype is more frequent among ND-MCI and non-amnestic subtype in T2D-MCI. In T2D-MCI, high HbA1c levels correlate with episodic memory (immediate recall) and T2D duration. Some indexes of episodic memory (immediate recall), attention, and visual-spatial ability correlate with insulin treatment. Conclusions: An association between T2D and non-amnestic MCI is suggested. In the T2D-MCI group, significant associations between insulin treatment and memory (immediate recall), complex figure copy, and attention were found.

The objective of our study was to demonstrate that living with a person affected by mild to moderate Alzheimer’s disease can lead to an increased perception of the caregiver’s burden using the Caregiver Burden Inventory (CBI). The sample consisted of 153 dyads, caregiver–patient. At baseline, a greater perception of the caregiver’s burden was observed in the live-in caregivers. A further increase in the total burden of the live-in caregivers was noticed at the 6-month follow-up. More specifically, with the inclusion of correction factors such as the caregiver’s age and the CBI subscales at baseline, the social and emotional burden becomes statistically significant ( P < .001). The present paper confirms our hypothesis that live-in caregivers perceive a greater burden than nonlive-in, and this difference increases further after 6 months. The difference in involvement between live-in and nonlive-in caregivers could be the foundation to tailor more specific interventions.

Background: Many studies have been underlined as care giving for people with Alzheimer’s disease (AD) is highly stressful and has significant negative consequences, such as anxiety and depression. Objective: The specific aim of our study is to establish whether a difference exists in the prevalence of depression of family caregivers of Alzheimer’s disease patients and healthy subjects not caregiver. Methods: Study group (n = 60) consists of caregivers of patients affected by Alzheimer’s disease, whereas control group (n = 120) consists of healthy individuals who are not care giving (from at least 5 years). All the subjects were subdivided on the basis of the following independent variables: sex, age, marital status and educational level. The subjects of study and control groups studied have filled in the following tests: IPAT CDQ e IPAT ASQ Tests by Cattell which describe depression and anxiety. Such tests have been validated on the adult and elderly Italian population. Statistical analysis: Student t test has been applied for the comparison between experimental and control groups. Results: The caregivers show higher levels of anxiety (medium to high, P < 0.001) and depression in comparison to the group of control (medium to high, P < 0.001). This result indicates the caregiver shows serious depression. Conclusions: The high levels of depression and anxiety suggest the following considerations: interventions of social and psychological support are fundamental not only to maintain the patient in the family nucleus but also to maintain the caregiver’s psychological health.

This study focuses on the spiritual well-being (SWB) of the family caregivers of cancer patients, examining the relationship with personality traits and quality of life (QoL) in palliative and curative care settings. All participants (n = 199) underwent the following self-report questionnaires: the Structural Analysis of Social Behavior (SASB)-Form A, the SWB Index, and the Medical Outcomes Study Short Form (SF-36). SWB scores were dichotomized at a cutoff corresponding to the 75th percentile. Statistical analysis: Student’s t test or by χ squared tests to compare high and low SWB and multivariate linear regression to estimate relations between SWB, SASB clusters (Cl), and QoL dimensions. Caregivers with high SWB reported significantly better scores than low SWB caregivers in the following SF-36 subscales: bodily pain (p = 0.035), vitality (p

Somatosensory evoked potentials (SEPs) of the pudendal nerve are a well-established diagnostic tool for the evaluation of pelvic floor disorders. However, the possible influence of sex differences on response latencies has not been established yet. The aim of this study was to standardize the procedures and to evaluate possible effects of gender differences on anal and penile/clitoral SEPs. The anal and dorsal penile/clitoral SEPs were recorded in 84 healthy subjects (40 males and 44 females; mean age 47.9 ± 16.6 years, range 16–81 years; mean height 168.3 ± 20.3 cm, range 155–187 cm). Pudendal SEPs were evoked with a bipolar surface electrode stimulating the clitoris or the base of the penis and the anal orifice and recorded using scalp electrodes. The latency of the first positive component (P1) was measured. The effect and possible interaction of (a) stimulation site and (b) gender on the two variables was explored by multivariate analysis of variance (MANOVA). The examination was well tolerated and a reproducible waveform of sufficient quality was obtained in all the subjects examined. In the female subjects, a mean cortical P1 latency of 37.0 ± 2.6 and 36.4 ± 3.2 ms for anal and clitoral stimulation, respectively, was found. In the male subjects, the cortical latencies were 38.0 ± 3.5 ms for the anal stimulation and 40.2 ± 3.7 ms for the penile stimulation. At MANOVA, a statistically significant main effect of stimulation site and gender as well as a significant interaction between the two variables was found. Anal and dorsal penile/clitoral SEPs represent a well-tolerated and reproducible method to assess the functional integrity of the sensory pathways in male and female subjects. Obtaining sex-specific reference data, by individual electrophysiological testing, is highly recommended because of significant latency differences between males and females, at least as far as penile/clitoral responses are concerned.

Background Sacral neuromodulation is becoming established as a valid treatment option for patients with anorectal disorders. Nevertheless, despite its efficacy, little is known regarding its mechanism of action. The purpose of this study was to evaluate whether chronic sacral neuromodulation is able to influence the expression of nitric oxide synthetase (NOS) in the anorectum of rats. Materials and methods Twenty-six female Sprague-Dawley rats were divided into three groups; normal control rats (n = 6); sham treatment (n =10) and group in whom, electrical sacral neuromodulation was performed (n = 10). Bilateral electrode wires were placed in the S1 and electrical stimulation was performed for 14 d. At the end of the procedures the rats were sacrificed, proctectomy was performed, and anorectal specimens were sent to the laboratory for immunostaining with n-NOS and i-NOS. Results In the anal and rectal specimens, n-NOS and i-NOS expression was significantly increased in epithelial and muscle cells after neuromodulation of the anus and rectum of the animals. Conclusion Our results showed that this model can be applied in further experimental studies to better understand the mechanism of action of sacral neuromodulation in anorectal disorders.

GRN, the gene coding for the progranulin (PGRN) protein, was recognized as a gene linked to frontotemporal lobar degeneration (FTLD). The first mutations identified were null mutations giving rise to haploinsufficiency. Missense mutations were subsequently detected, but only a small subset has been functionally investigated. We identified missense mutations (C105Y, A199V, and R298H) in FTLD cases with family history and/or with low plasma PGRN levels. The aim of this study was to determine their pathogenicity. We performed functional studies, analyzing PGRN expression, secretion, and cleavage by elastase. GRN C105Y affected both secretion and elastase cleavage, likely representing a pathogenic mutation. GRN A199V did not alter the physiological properties of PGRN and GRN R298H produced only moderate effects on PGRN secretion, indicating that their pathogenicity is uncertain. In the absence of strong segregation data and neuropathological examinations, genetic, biomarker, and functional studies can be applied to an algorithm to assess the likelihood of pathogenicity for a mutation. This information can improve our understanding of the complex mechanisms by which GRN mutations lead to FTLD.

Aims The aim of this study is to present the normative data of direct and reflex motor anal sphincter responses, simultaneously evoked by S3 surface electrical stimulation. By this method, it is possible to test the functional integrity of the nervous pathways activated during sacral neuromodulation (SNM). Methods Twenty healthy subjects were studied. Motor-evoked potentials (MEPs) were recorded by concentric needle electrode from external anal sphincter (EAS). Electrical stimulation was applied by means of a bipolar surface electrode over the S3 right or left sacral foramina. Results Direct (R1) and reflex responses (R2 and R3) were found at latencies of 6.98, 25.12, and 50.31 msec, respectively. The two first responses were recorded in all the cases; the last response is steadily recorded in 17 out of 20 subjects. Conclusions Our data can serve as reference values for future study in patients with pelvic floor dysfunction. EAS responses following S3 percutaneous electrical stimulation can represent a useful aid in the selection of candidates to SNM. Neurourol. Urodynam. 25:788–791, 2006. © 2006 Wiley-Liss, Inc.

This chapter details the neural circuitry that controls the mechanisms that regulate urinary and intestinal functions, describing the afferent and efferent neuronal pathways between the brain and the pelvic organs.

Electrophysiological activation of the motor pathways can be obtained by electrical or magnetic stimulation. The latter has the great advantage of being painful and able to stimulate deeply situated nervous structures. Only a few reports describe responses obtained from pelvic floor muscles and external anal sphincter (EAS) by transcranial and lumbo-sacral magnetic stimulation. Our purpose is to present normative data of motor evoked responses from EAS in a group of healthy subjects (age range 19–80 years) using a standardized protocol of magnetic stimulation. Nine females and 7 males, with a mean age of 52.63 years, were included in this study. They had no known neurological and gastrointestinal disease. Magnetic shocks were delivered by a Magstim 200 (Novametrix) and a circular coil, centered on the vertex and on the lumbo-sacral region. Electromyographic recordings were taken from EAS using needle electrodes. The cortical magnetic stimulation was performed in two conditions: at rest and during a mild contraction of pelvic floor muscles. The mean values of motor evoked potentials (MEPs) latencies after cortical stimulation were 26.92±3.01 ms at rest and 23.31±2.70 ms during facilitation. Motor latency after lumbo-sacral root stimulation was 6.09±1.43 ms. The MEPs from EAS are easily obtained and stably reproducible in normal subjects. It can be suggested also as a useful adjunct in the assessment of faecal incontinence.

We report the clinical and electrophysiological findings of isolated stretch-induced accessory nerve palsy obtained by using conventional technique compared to magnetic stimulation at the base of the skull. The same methods of magnetic stimulation were applied in 10 healthy volunteers, to determine normal limits of amplitude and latency of the motor responses. The clinical features of the isolated spinal accessory nerve palsy are weakness of the sternocleidomastoid muscle and of the three portions of trapezius muscle. Most commonly reported etiologies include surgical manipulation and excision in the posterior triangle of the neck. Less frequently the cause is represented by radiation procedures, shoulder traction, penetrating, blunt or stretch injuries; this last etiology is extremely rare. The use of conventional electrophysiological methods to evaluate injuries of the nerves leaving the base of the skull is limited by the difficulty in obtaining an adequate electrical surface stimulation necessitating the use of needle electrodes. Moreover, conventional electrical stimulation often causes significant discomfort to the patient. The magnetic coil stimulation at the base of the skull is a new alternative painless technique that permits to elicit motor responses, by stimulating deeply situated nerves and, in particular, the accessory nerve, resulting as a useful electrodiagnostic tool.

Fecal incontinence, according to the most used definition, is the “involuntary loss of the stool or soiling at a socially inappropriate time or place” [1]. It is an important health issue that strongly affects patient quality of life and restricts their social activities. It is a common problem, with prevalence ranging from 2.2% to 15% in the community and up to 40% in nursing homes [2]. The prevalence of fecal incontinence in neurological patients is higher than in the general population. Many neurological disorders are associated with fecal incontinence, and this chapter is a review of the current clinical knowledge regarding the pathogenesis and clinical findings. When considering the possible effects of central and peripheral neurological lesions on fecal continence, it is important to keep in mind that continence depends on intact neural pathways and normal function of the cerebral, spinal, and cauda equina centers, and peripheral nerves. It should be remembered, however, that signs, symptoms, and gastrointestinal dysfunction may differ from expectations by virtue of incomplete neuronal lesions, coexisting involvement of supraspinal or spinal centers, or damage to the distal parts of the autonomic or somatic innervation of the pelvic floor sphincter muscles.

Sacral neuromodulation is a new treatment for refractory voiding disorders such as urge incontinence, urinary retention, frequency-urgency syndromes and faecal incontinence. The current approach to sacral nerve stimulation consists of a two-stage procedure. The first is a PNE test (Percutaneous Nerve Evaluation) by a provisional electrically stimulated spinal needle, placed percutaneously in the S3 foramina for four to ten days. If successful, the second stage, permanent implantation, is carried out. The PNE test is performed under fluoroscopic control using the palpable bony sacral foramina as referral points. This technique can show some limitations, such as operator Rx exposure, poor visualization of sacral foramina because of bowel gas artefacts or sacral malformation. In order to reduce these inconveniences and to improve efficiency of the test we tried an alternative technique. The purpose of our study was to test the use of CT as an alternative technique in order to evaluate its advantages and possible routine use.We tested 30 patients with the PNE test under CT guidance (16 males and 14 females) suffering from serious pelvic disorders and not responding to the normal therapeutic regime. Twenty-seven patients showed relative anatomical integrity of the pelvis and the sacrum, the remaining 3 patients presented morphological anomalies of the sacral foramina. With the patient in the prone position the sacral foramina were identified with CT volumetric scanning using a spiral CT scanner equipped with a second console for the three-dimensional reconstructions. Having identified the location of the S3 foramina, a sterile field was prepared and the spinal needle introduced checking correct positioning with a CT control scan. An electrode was then inserted after having checked correct muscular contractile response and the precise position with a further CT scan.Thirty patients were subjected to PNE under CT guidance for a total of 38 centerings. Eight patients underwent the PNE procedure on both the S3 foramina. The sacral foramen was centred at the first attempt in 36 out of 38 cases. Two cases required several attempts to centre correctly the foramen. In 4 patients out of 30 a second electrode was implanted. In one patient who had a nonconsolidated sacral fracture, CT guidance enabled insertion of the electrode inside the only practicable foramen, a manoeuvre that would have been impossible with fluoroscopical guidance. Only once was the electrode placed in a wrong location but promptly repositioned after a CT control. During the whole trial period we had a positive response to the PNE test in 18 out of 30 patients (60%), a partial response in 4 out of 30 patients and a negative response in the remaining 8 patients. None of the patients who underwent the PNE test had infectious complications and the procedure was well tolerated by all. The procedure lasted about 45 minutes.

We read with interest the article by Abercrombie et al which describes the pathophysiology and surgical management of faecal incontinence in two siblings with severe myotonic dystrophy.1 In the authors’ experience, long term results of both medical and surgical management of the faecal incontinence were unsatisfactory, as proved by the fact that postanal sphincter repair restored faecal continence only for a brief time. The authors’ pessimistic conclusions suggest that “faecal incontinence in myotonic dystrophy is difficult to relieve by any currently available treatment other than colostomy”. It should be noted, however, that the …