Adaptive Deep Brain Stimulation in Parkinson's Disease: A Delphi Consensus Study.

Importance: If history teaches, as cardiac pacing moved from fixed-rate to on-demand delivery in in 80s of the last century, there are high probabilities that closed-loop and adaptive approaches will become, in the next decade, the natural evolution of conventional Deep Brain Stimulation (cDBS). However, while devices for aDBS are already available for clinical use, few data on their clinical application and technological limitations are available so far. In such scenario, gathering the opinion and expertise of leading investigators worldwide would boost and guide practice and research, thus grounding the clinical development of aDBS. Observations: We identified clinical and academically experienced DBS clinicians (n=21) to discuss the challenges related to aDBS. A 5-point Likert scale questionnaire along with a Delphi method was employed. 42 questions were submitted to the panel, half of them being related to technical aspects while the other half to clinical aspects of aDBS. Experts agreed that aDBS will become clinical practice in 10 years. In the present scenario, although the panel agreed that aDBS applications require skilled clinicians and that algorithms need to be further optimized to manage complex PD symptoms, consensus was reached on aDBS safety and its ability to provide a faster and more stable treatment response than cDBS, also for tremor-dominant Parkinson's disease patients and for those with motor fluctuations and dyskinesias. Conclusions and Relevance: Despite the need of further research, the panel concluded that aDBS is safe, promises to be maximally effective in PD patients with motor fluctuation and dyskinesias and therefore will enter into the clinical practice in the next years, with further research focused on algorithms and markers for complex symptoms.

Physical therapy in patients with Parkinson's disease treated with Deep Brain Stimulation: a Delphi panel study.

Although deep brain stimulation of the subthalamic nucleus (STN-DBS) induces motor benefits in people with Parkinson's disease (PwPD), the size and duration of the effects of STN-DBS on motor axial (e.g., postural instability, trunk posture alterations) and gait impairments (e.g., freezing of gait - FOG) are still ambiguous. Physical therapy (PT) effectively complements pharmacological treatment to improve postural stability, gait performance, and other dopamine-resistant symptoms (e.g. festination, hesitation, axial motor dysfunctions, and FOG) in PwPD who are non-surgically treated. Despite the potential for positive adjuvant effects of PT following STN-DBS surgery, there is a paucity of science available on the topic. In such a scenario, gathering the opinion and expertise of leading investigators worldwide was pursued to study motor rehabilitation in PwPD following STN-DBS. After summarizing the few available findings through a systematic review, we identified clinical and academically experienced DBS clinicians (n=21) to discuss the challenges related to PT following STN-DBS. A 5-point Likert scale questionnaire was used and based on the results of the systematic review along with a Delphi method. Thirty-nine questions were submitted to the panel - half related to general considerations on PT following STN-DBS, half related to PT treatments. Despite the low-to-moderate quality, the few available rehabilitative studies suggested that PT could improve dynamic and static balance, gait performance and posture. Similarly, panellists strongly agreed that PT might help in improving motor symptoms and quality of life, and it may be possibly prescribed to maximize the effects of the stimulation. The experts agreed that physical therapists could be part of the multidisciplinary team taking care of the patients. Also, they agreed on prescribing of conventional PT, but not massage or manual therapy. Our results will inform the rehabilitation and the DBS community to engage, publish and deepen this area of research. Such efforts may spark guidelines for PT following STN-DBS.

Assessment of quality of life on home parenteral nutrition and after intestinal transplantation using treatment-specific questionnaires.

In order to investigate the quality of life on home parenteral nutrition and after intestinal transplantation using comparable questionnaires, the treatment-specific quality of life questionnaire for adult patients on home parenteral nutrition was adapted for intestinal transplant recipients. Both instruments were composed of 8 functional scales, 9 symptom scales, 3 global health status/quality of life scales and 2 single items. A preliminary cross-sectional study enrolling all the patients currently cared at the same hospital was carried out. Exclusion criteria were age ≥ 60 years and hospitalization at time of assessment. Thirty-three home parenteral nutrition patients (100% answered) and 22 intestinal transplant recipients (82% answered) were enrolled. Intestinal transplant recipients showed a better score in following scales: ability to holiday/travel (p < 0.001), fatigue (p = 0.022), gastrointestinal symptoms (p < 0.001), stoma management/bowel movements (p = 0.001) and global health status/quality of life (p = 0.012). A better score for ability to eat/drink (p = 0.070) and a worse score for sleep pattern (p = 0.100) after intestinal transplantation were also observed. The results of this preliminary study with specific instruments were consistent with the main expected improvement of the quality of life related to intestinal transplantation. Further studies in larger patient cohorts are required to confirm these data.

Static versus dynamic heterogeneities in the D = 3 Edwards-Anderson-Ising spin glass.

We numerically study the aging properties of the dynamical heterogeneities in the Ising spin glass. We find that a phase transition takes place during the aging process. Statics-dynamics correspondence implies that systems of finite size in equilibrium have static heterogeneities that obey finite-size scaling, thus signaling an analogous phase transition in the thermodynamical limit. We compute the critical exponents and the transition point in the equilibrium setting, and use them to show that aging in dynamic heterogeneities can be described by a finite-time scaling ansatz, with potential implications for experimental work.

Structural and functional motor cortex asymmetry in unilateral lower limb amputation with phantom limb pain.

OBJECTIVE: The role of motor cortex reorganization in the development and maintenance of phantom limb pain (PLP) is still unclear. This study aims to evaluate neurophysiological and structural motor cortex asymmetry in patients with PLP and its relationship with pain intensity. METHODS: Cross-sectional analysis of an ongoing randomized-controlled trial. We evaluated the motor cortex asymmetry through two techniques: i) changes in cortical excitability indexed by transcranial magnetic stimulation (motor evoked potential, paired-pulse paradigms and cortical mapping), and ii) voxel-wise grey matter asymmetry analysis by brain magnetic resonance imaging. RESULTS: We included 62 unilateral traumatic lower limb amputees with a mean PLP of 5.9 (SD = 1.79). We found, in the affected hemisphere, an anterior shift of the hand area center of gravity (23 mm, 95% CI 6 to 38, p = 0.005) and a disorganized and widespread representation. Regarding voxel-wise grey matter asymmetry analysis, data from 21 participants show a loss of grey matter volume in the motor area of the affected hemisphere. This asymmetry seems negatively associated with time since amputation. For TMS data, only the ICF ratio is negatively correlated with PLP intensity (r = -0.25, p = 0.04). CONCLUSION: There is an asymmetrical reorganization of the motor cortex in patients with PLP, characterized by a disorganized, widespread, and shifted hand cortical representation and a loss in grey matter volume in the affected hemisphere. This reorganization seems to reduce across time since amputation. However, it is not associated with pain intensity. SIGNIFICANCE: These findings are significant to understand the role of the motor cortex reorganization in patients with PLP, showing that the pain intensity may be related with other neurophysiological factors, not just cortical reorganization.

Pre- and Post-Transfusion Alloimmunization in Dogs Characterized by 2 Antiglobulin-Enhanced Cross-match Tests.

BACKGROUND: When dogs are transfused, blood compatibility testing varies widely but may include dog erythrocyte antigen (DEA) 1 typing and rarely cross-matching. OBJECTIVES: Prospective study to examine naturally occurring alloantibodies against red blood cells (RBCs) and alloimmunization by transfusion using 2 antiglobulin-enhanced cross-match tests. ANIMALS: Eighty client-owned anemic, 72 donor, and 7 control dogs. METHODS: All dogs were typed for DEA 1 and some also for DEA 4 and DEA 7. Major cross-match tests with canine antiglobulin-enhanced immunochromatographic strip and gel columns were performed 26-129 days post-transfusion (median, 39 days); some dogs had an additional early evaluation 11-22 days post-transfusion (median, 16 days). Plasma from alloimmunized recipients was cross-matched against RBCs from 34 donor and control dogs. RESULTS: The 2 cross-match methods gave entirely concordant results. All 126 pretransfusion cross-match results for the 80 anemic recipients were compatible, but 54 dogs died or were lost to follow up. Among the 26 recipients with follow-up, 1 dog accidently received DEA 1-mismatched blood and became cross-match-incompatible post-transfusion. Eleven of the 25 DEA 1-matched recipients (44%) became incompatible against other RBC antigens. No naturally occurring anti-DEA 7 alloantibodies were detected in DEA 7- dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: The antiglobulin-enhanced immunochromatographic strip cross-match and laboratory gel column techniques identified no naturally occurring alloantibodies against RBC antigens, but a high degree of post-transfusion alloimmunization in dogs. Cross-matching is warranted in any dog that has been previously transfused independent of initial DEA 1 typing and cross-matching results before the first transfusion event.

Quality of life on home parenteral nutrition or after intestinal transplantation.

AIM: We compared the health related quality of life (HRQOL) of stable patients on home parenteral nutrition (HPN) and of patients who underwent successful intestinal transplantation (ITx). METHODS: HRQOL was evaluated by the non-disease-specific Short Form 36 instrument, which examines eight specific domains and scores them on a scale of 0% to 100%. Patient scores were standardized for the sex-matched and age-matched group scores of the healthy population by calculating the Z-score (reduced value: Z-score < -1). RESULTS: Eighteen patients on HPN and 12 patients who underwent ITx were studied. The two groups did not differ for primary intestinal disease, cause of intestinal failure, presence of a stoma, body mass index, and employment and marital status. HPN Z-scores were physical functioning -2.3, physical role -1.5, body pain -1.0, general health -1.2, vitality -0.5, social functioning -0.9, emotional role -0.7, and mental health 0.0. ITx Z-scores were physical functioning -1.7, physical role -0.8, body pain 0.0, general health -0.4, vitality 0.0, social functioning -0.4, emotional role -0.3, and mental health 0.0. Only the body pain Z-scores differed significantly (P = .012). CONCLUSIONS: The value of the physical components of the SF-36 was reduced in all the components in the HPN patients and in the physical functioning component in the ITx patients. The mental health components were normal in both. Successful ITx showed a better subjective physical health feeling than stable HPN.

The SF-36 instrument for the follow-up of health-related quality-of-life assessment of patients undergoing home parenteral nutrition for benign disease.

INTRODUCTION: The non-disease-specific SF-36 instrument was applied to detect changes in quality of life among patients at a single center who were receiving home parenteral nutrition (HPN) for intestinal failure. METHODS: All HPN patients completed the questionnaire during routine visits. The SF-36 examines eight domains (scores: 0% to 100%): physical functioning (PF), role-functioning physical (RP), body pain (BP), general health (GH), vitality (VT), social functioning (SF), as well as role-functioning emotional (RE) and mental health (MH). Patient responses were standardized for the sex- and age-matched group scores of the healthy population by calculating the Z-score: (healthy population mean score - patient raw score)/healthy population standard deviation (reduced value: Z-score < -1). A difference in a domain score was considered significant in the individual patient if it was greater than the 90% confidence interval for healthy subjects and if it produced a change in Z-score category. General, sociodemographic, underlying disease and HPN-related factors were collected. RESULTS: For 31 enrolled adult patients, the baseline mean Z-score was reduced in five domains: PF, RP, BP, GH and SF. Twenty patients underwent a second SF-36 assessment 10 +/- 2 months later: the HRQOL worsened in eight and improved in 10 (no. worsened domains > no. improved or vice versa). The worsened subgroup showed a decrease in body mass index (P =.104), an increase in the number of HPN infusions per week (P =.065), and a greater incidence of intestinal motility disorders (P =.161), of liquid oral diet (P =.027), and of nycturia (P =.028). CONCLUSIONS: The SF-36 instrument reflecting the generic HRQOL assessment may be a suitable tool for patients on HPN.

Nonequilibrium spin-glass dynamics from picoseconds to a tenth of a second.

We study numerically the nonequilibrium dynamics of the Ising spin glass, for a time spanning 11 orders of magnitude, thus approaching the experimentally relevant scale (i.e., seconds). We introduce novel analysis techniques to compute the coherence length in a model-independent way. We present strong evidence for a replicon correlator and for overlap equivalence. The emerging picture is compatible with noncoarsening behavior.

Long-term results of topical immunotherapy in children with alopecia totalis or alopecia universalis.

BACKGROUND: Topical immunotherapy has been used in the treatment of children with alopecia areata with encouraging results. OBJECTIVE: Our purpose was to determine the long-term results in 33 children with severe alopecia areata treated with topical immunotherapy. METHODS: From 1983 to 1989 we treated 33 children with topical immunotherapy with squaric acid dibutylester. RESULTS: Complete hair regrowth was observed in 10 children (30.3%). During the follow-up period (mean, 5.9 years; range, 4 to 12 years), 7 of these 10 patients had severe relapses that were not responsive to further treatment. Only three clinically benefited from topical immunotherapy. Two maintained complete hair regrowth after treatment was stopped. CONCLUSION: Our results indicate that only a small proportion of children with severe alopecia areata will obtain a persistent benefit from topical immunotherapy.

Diffuse partial woolly hair.

We report here a 14-year-old girl with diffuse partial woolly hair. The patient presented mild hair loss associated with the presence of fine, short and kinky hairs closely interspersed with the normal hair throughout the scalp. The pathology of the scalp revealed the presence of intermediate-sized hair follicles regularly intermingled with normal follicles in each follicular unit. The possibility that diffuse partial woolly hair may result from a progressive miniaturization of the hair follicles may explain the presence of evident hair thinning in several adult patients affected by this rare abnormality.

Penile Crohn's disease: a case report.

Metastatic Crohn's disease is a rare inflammatory condition characterised by cutaneous granulomatous lesions separated from the affected bowel by normal intact skin. Involvement of the genitalia in Crohn's disease is rare and consists of ulcerated lesions in almost all of the cases reported in the literature. We describe a case of penile involvement in a 27 year old man with a 5 year history of Crohn's disease. Should genital involvement precede the bowel disease, patients may consult the sexually transmitted disease service for this problem and the dermatovenereologists may be the first to formulate the diagnosis.