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Background and Objectives: Current formulations of primary progressive aphasia (PPA) derive largely from English-speaking patients. We hypothesized that language-specific characteristics influence PPA phenotypes in 2 contrasting languages: Italian and English., Methods: We undertook a retrospective, cross-sectional, observational comparison of 2 patient cohorts representing all major PPA syndromes, in London and Florence. Neuropsychological scores in a range of linguistic and general cognitive domains were normalized to native speaker controls and dichotomized as impaired/unimpaired. Proportions were compared using χ 2 tests and adjusted for symptom duration and severity of cognitive impairment using logistic regression., Results: The cohorts comprised 106 (48.1% female) Italian speakers (14 nonfluent/agrammatic [nfvPPA], 20 semantic [svPPA], 41 logopenic variant [lvPPA], 31 mixed PPA [mPPA]) and 166 (45.2% female) English speakers (70 nfvPPA, 45 svPPA, 42 lvPPA, 9 mPPA). Comparing cohorts, the English cohort was younger (mean 62.7 [SD = 8.4] vs 65.9 [7.8] years; p = 0.003, Cohen d = 0.39), with longer symptom duration (4.6 [4.3] vs 3.1 [2.5] years; p = 0.048, d = 1.08), a higher proportion of nfvPPA cases (42% vs 13%, χ 2 = 25.4, p < 0.001), and lower proportions of lvPPA (25% vs 38%, χ 2 = 5.46, p = 0.019) and mPPA (5% vs 29%, χ 2 = 29.3, p < 0.001). English-speaking nfvPPA patients had less frequent expressive agrammatism (46% vs 93%, p = 0.015, odds ratio [OR] 16.05, 95% CI 1.70-151.13) but more frequently impaired single-word comprehension (60% vs 8%, p = 0.013, OR 0.06, 95% CI 0.00-0.56). English svPPA patients had more frequent surface dyslexia (68% vs 30%, p = 0.046, OR 0.24, 95% CI 0.06-0.97) and dysgraphia (38% vs 10%, p = 0.021, OR 0.09, 95% CI 0.01-0.70) while English lvPPA patients had more frequently impaired single-word comprehension (89% vs 29%, p < 0.001, OR 0.05, 95% CI 0.01-0.28), word repetition (61% vs 26%, p = 0.020, OR 0.24, 95% CI 0.07-0.80), nonword repetition (78% vs 30%, p = 0.010, OR 0.18, 95% CI 0.05-0.06), nonverbal working memory (69% vs 36%, p = 0.005, OR 0.10, 95% CI 0.02-0.51), and visuomotor function (89% vs 25%, p < 0.001, OR 0.02, 95% CI 0.01-0.20)., Discussion: Language-specific characteristics influenced PPA phenotypes, with more frequent expressive agrammatism in Italian (reflecting its morphologic complexity), more frequently impaired word processing in English (reflecting its articulatory, acoustic, and orthographic complexity), and increased prevalence of mPPA in Italian. These findings have implications for PPA diagnosis and management. Limitations of test heterogeneity and cohort size should be addressed in future, prospective, multicenter initiatives using cross-linguistic tools.

We aimed to assess diagnostic accuracy of plasma p-tau181 and NfL separately and in combination in discriminating Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI) patients carrying Alzheimer's Disease (AD) pathology from non-carriers; to propose a flowchart for the interpretation of the results of plasma p-tau181 and NfL. We included 43 SCD, 41 MCI and 21 AD-demented (AD-d) patients, who underwent plasma p-tau181 and NfL analysis. Twenty-eight SCD, 41 MCI and 21 AD-d patients underwent CSF biomarkers analysis (Aβ1-42, Aβ1-42/1-40, p-tau, t-tau) and were classified as carriers of AD pathology (AP+) it they were A+/T+ , or non-carriers (AP-) when they were A-, A+/T-/N-, or A+/T-/N+ according to the A/T(N) system. Plasma p-tau181 and NfL separately showed a good accuracy (AUC = 0.88), while the combined model (NfL + p-tau181) showed an excellent accuracy (AUC = 0.92) in discriminating AP+ from AP- patients. Plasma p-tau181 and NfL results were moderately concordant (Coehn's k = 0.50, p < 0.001). Based on a logistic regression model, we estimated the risk of AD pathology considering the two biomarkers: 10.91% if both p-tau181 and NfL were negative; 41.10 and 76.49% if only one biomarker was positive (respectively p-tau18 and NfL); 94.88% if both p-tau181 and NfL were positive. Considering the moderate concordance and the risk of presenting an underlying AD pathology according to the positivity of plasma p-tau181 and NfL, we proposed a flow chart to guide the combined use of plasma p-tau181 and NfL and the interpretation of biomarker results to detect AD pathology., (© 2024. The Author(s).)

Mixed primary progressive aphasia (mPPA) accounts for a substantial proportion of primary progressive aphasia (PPA) cases. However, the lack of a standardised definition of this condition has resulted in misclassification of PPA cases. In this study, we enrolled 55 patients diagnosed with PPA, comprising 12 semantic variant (svPPA), 23 logopenic variant (lvPPA), and 20 mPPA cases with linguistic characteristics consistent with both svPPA and lvPPA (s/lvPPA). All patients underwent language assessments, evaluation of Alzheimer's disease biomarkers (via cerebrospinal fluid analysis or Amyloid-PET), and 18 F-FDG-PET brain scans. An agglomerative hierarchical clustering (AHC) analysis based on linguistic characteristics revealed two distinct clusters within the s/lvPPA group: cluster k1 (n = 10) displayed an AD-like biomarker profile, with lower levels of Aβ 42 and Aβ 42 /Aβ 40 ratio, along with higher levels of t-tau and p-tau compared to cluster k2 (n = 10). Interestingly, k1 exhibited linguistic features that were similar to those of svPPA. Both clusters exhibited extensive temporoparietal hypometabolism. These findings support the hypothesis that a subgroup of s/lvPPA may represent a clinical manifestation of AD-related PPA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Little is known about empathy changes from the early stages of Alzheimer's Disease (AD) continuum. The aim of this study is to investigate empathy across AD spectrum from Subjective Cognitive Decline (SCD) to Mild Cognitive Impairment (MCI) and AD dementia (AD-d). Forty-five SCD, 83 MCI and 80 AD-d patients were included. Empathy was assessed by Interpersonal Reactivity Index (IRI) (Perspective Taking - PT, Fantasy - FT, Empathic Concern - EC, and Personal Distress - PD), rated by caregivers before (T0) and after (T1) cognitive symptoms' onset. IRI was also administered to SCD patients to have a self-reported empathy evaluation. Facial emotion recognition was assessed by Ekman-60 Faces Test. Twenty-two SCD, 54 MCI and 62 AD-d patients underwent CSF biomarkers analysis and were classified as carriers of AD pathology (AP+) when they were A+/T+ (regardless of N), or non-carriers (AP-) when they were A- (regardless of T and N), or A+/T-/N-, or A+/T-/N+ according to the A/T(N) system. Cerebral FDG-PET SPM analysis was used to explore neural correlates underlying empathy deficits. PD scores significantly increased from T0 to T1 in SCD, MCI and AD-d (p < .001), while PT scores decreased in MCI and in AD-d (p < .001). SCD AP+ showed a greater increase in PD scores over time (ΔPD T0 - T1) than SCD AP- (p < .001). SCD self-reported PT scores were lower than those of general Italian population (14.94 ± 3.94, 95% C.I. [13.68-16.20] vs 17.70 ± 4.36, 95% C.I. [17.30-18.10]). In AD continuum (SCD AP+, MCI AP+, AD-d), a positive correlation was detected between PT-T1 and brain metabolism in left posterior cingulate gyrus, precuneus and right frontal gyri; a negative correlation was found between ΔPT and brain metabolism in bilateral posterior cingulate gyri. PT may be subtly involved since the preclinical phase of AD. Changes over time of PD are influenced by the underlying Alzheimer's pathology and could potentially serve as an early AD neuropsychological marker., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction and Aim: NfL and GFAP are promising blood-based biomarkers for Alzheimer's disease. However, few studies have explored plasma GFAP in the prodromal and preclinical stages of AD. In our cross-sectional study, our aim is to investigate the role of these biomarkers in the earliest stages of AD., Materials and Methods: We enrolled 40 patients (11 SCD, 21 MCI, 8 AD dementia). All patients underwent neurological and neuropsychological examinations, analysis of CSF biomarkers (Aβ 42 , Aβ 42 /Aβ 40 , p-tau, t-tau), Apolipoprotein E (APOE) genotype analysis and measurement of plasma GFAP and NfL concentrations. Patients were categorized according to the ATN system as follows: normal AD biomarkers (NB), carriers of non-Alzheimer's pathology (non-AD), prodromal AD, or AD with dementia (AD-D)., Results: GFAP was lower in NB compared to prodromal AD (p = 0.003, d = 1.463) and AD-D (p = 0.002, d = 1.695). NfL was lower in NB patients than in AD-D (p = 0.011, d = 1.474). NfL demonstrated fair accuracy (AUC = 0.718) in differentiating between NB and prodromal AD, with a cut-off value of 11.65 pg/mL. GFAP showed excellent accuracy in differentiating NB from prodromal AD (AUC = 0.901) with a cut-off level of 198.13 pg/mL., Conclusions: GFAP exhibited excellent accuracy in distinguishing patients with normal CSF biomarkers from those with prodromal AD. Our results support the use of this peripheral biomarker for detecting AD in patients with subjective and objective cognitive decline., (© 2023. The Author(s).)

Background and Purpose: We aimed to evaluate the accuracy of plasma neurofilament light chain (NfL) in predicting Alzheimer's disease (AD) and the progression of cognitive decline in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI)., Methods: This longitudinal cohort study involved 140 patients (45 with SCD, 73 with MCI, and 22 with AD dementia [AD-D]) who underwent plasma NfL and AD biomarker assessments (cerebrospinal fluid, amyloid positron emission tomography [PET], and 18 F-fluorodeoxyglucose-PET) at baseline. The patients were rated according to the amyloid/tau/neurodegeneration (A/T/N) system and followed up for a mean time of 2.72 ± 0.95 years to detect progression from SCD to MCI and from MCI to AD. Forty-eight patients (19 SCD, 29 MCI) also underwent plasma NfL measurements 2 years after baseline., Results: At baseline, plasma NfL detected patients with biomarker profiles consistent with AD (A+/T+/N+ or A+/T+/N-) with high accuracy (area under the curve [AUC] 0.82). We identified cut-off values of 19.45 pg/mL for SCD and 20.45 pg/mL for MCI. During follow-up, nine SCD patients progressed to MCI (progressive SCD [p-SCD]), and 14 MCI patients developed AD dementia (progressive MCI [p-MCI]). The previously identified cut-off values provided good accuracy in identifying p-SCD (80% [95% confidence interval 65.69: 94.31]). The rate of NfL change was higher in p-MCI (3.52 ± 4.06 pg/mL) compared to non-progressive SCD (0.81 ± 1.25 pg/mL) and non-progressive MCI (-0.13 ± 3.24 pg/mL) patients. A rate of change lower than 1.64 pg/mL per year accurately excluded progression from MCI to AD (AUC 0.954)., Conclusion: Plasma NfL concentration and change over time may be a reliable, non-invasive tool to detect AD and the progression of cognitive decline at the earliest stages of the disease., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: The aim of this study is to investigate the role of plasma phosphorylated tau (p-tau) 181 as a potential biomarker for Alzheimer's Disease (AD) pathology in the early stages of the disease, as a valuable marker for tauopathy., Materials and Methods: Thirty-three Subjective Cognitive Decline (SCD), 32 Mild Cognitive Impairment (MCI) and 14 AD demented (AD-d) patients underwent plasma p-tau181 analysis with SiMoA assay. Twenty-six SCD, 32 MCI and 14 AD-d patients also underwent CSF biomarkers analysis (Aβ1-42, Aβ1-42/1-40, p-tau, t-tau) and were classified as carriers of AD pathology (AP+) when A+ was associated with T+ (regardless of N), or non-carriers (AP-) when they were A- (regardless of T and N), or A+/T-/N-, or A+/T-/N+ according to the A/T(N) system., Results: Plasma p-tau181 levels were higher in SCD AP+ than in SCD AP- (2.85 ± 0.53 vs 1.73 ± 0.64, p < 0.001), and in MCI AP+ than in MCI AP- (4.03 ± 1.07 vs 2.04 ± 0.87, p < 0.001). In a multivariate linear regression analysis, AP status was the only variable that influenced plasma p-tau181 (B = 1.670 [95% CI 1.097:2.244], p < 0.001). Plasma p-tau181 was highly accurate for discriminating between AP+ and AP- patients (AUC = 0.910). We identified a cut-off level of 2.69 pg/mL to distinguish between AP+ and AP- (sensibility 0.86, specificity 0.82, PPV 75.00% NPV 90.32%)., Conclusions: Plasma p-tau181 levels were influenced by the presence of underlying AD pathology, independently from the cognitive status and were highly accurate in differentiating SCD-MCI patients who were carriers of AD pathology from non-carriers. Plasma p-tau181 might be a promising non-invasive biomarker of AD pathology at a very early stage., Competing Interests: Declaration of Competing Interest The authors have nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: As disease-modifying therapies (DMTs) for Alzheimer's disease (AD) are becoming a reality, there is an urgent need to select cost-effective tools that can accurately identify patients in the earliest stages of the disease. Subjective Cognitive Decline (SCD) is a condition in which individuals complain of cognitive decline with normal performances on neuropsychological evaluation. Many studies demonstrated a higher prevalence of Alzheimer's pathology in patients diagnosed with SCD as compared to the general population. Consequently, SCD was suggested as an early symptomatic phase of AD. We will describe the study protocol of a prospective cohort study (PREVIEW) that aim to identify features derived from easily accessible, cost-effective and non-invasive assessment to accurately detect SCD patients who will progress to AD dementia., Methods: We will include patients who self-referred to our memory clinic and are diagnosed with SCD. Participants will undergo: clinical, neurologic and neuropsychological examination, estimation of cognitive reserve and depression, evaluation of personality traits, APOE and BDNF genotyping, electroencephalography and event-related potential recording, lumbar puncture for measurement of Aβ 42 , t-tau, and p-tau concentration and Aβ 42 /Aβ 40 ratio. Recruited patients will have follow-up neuropsychological examinations every two years. Collected data will be used to train a machine learning algorithm to define the risk of being carriers of AD and progress to dementia in patients with SCD., Discussion: This is the first study to investigate the application of machine learning to predict AD in patients with SCD. Since all the features we will consider can be derived from non-invasive and easily accessible assessments, our expected results may provide evidence for defining cost-effective and globally scalable tools to estimate the risk of AD and address the needs of patients with memory complaints. In the era of DMTs, this will have crucial implications for the early identification of patients suitable for treatment in the initial stages of AD., Trial Registration Number (trn): NCT05569083., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The aims of the study were to assess empathy deficit and neuronal correlates in logopenic primary progressive aphasia (lv-PPA) and compare these data with those deriving from amnesic Alzheimer's disease (AD). Eighteen lv-PPA and thirty-eight amnesic AD patients were included. Empathy in both cognitive and affective domains was assessed by Informer-rated Interpersonal Reactivity Index (perspective taking, PT, and fantasy, FT, for cognitive empathy; empathic concern, EC, and personal distress, PD, for affective empathy) before (T0) and after (T1) cognitive symptoms' onset. Emotion recognition was explored through the Ekman 60 Faces Test. Cerebral FDG-PET was used to explore neural correlates underlying empathy deficits. From T0 to T1, PT scores decreased, and PD scores increased in both lv-PPA (PT z = -3.43, p = 0.001; PD z = -3.62, p < 0.001) and in amnesic AD (PT z = -4.57, p < 0.001; PD z = -5.20, p < 0.001). Delta PT (T0-T1) negatively correlated with metabolic disfunction of the right superior temporal gyrus, fusiform gyrus, and middle frontal gyrus (MFG) in amnesic AD and of the left inferior parietal lobule (IPL), insula, MFG, and bilateral superior frontal gyrus (SFG) in lv-PPA ( p < 0.005). Delta PD (T0-T1) positively correlated with metabolic disfunction of the right inferior frontal gyrus in amnesic AD ( p < 0.001) and of the left IPL, insula, and bilateral SFG in lv-PPA ( p < 0.005). Lv-PPA and amnesic AD share the same empathic changes, with a damage of cognitive empathy and a heightening of personal distress over time. The differences in metabolic disfunctions correlated with empathy deficits might be due to a different vulnerability of specific brain regions in the two AD clinical presentations., Competing Interests: The authors declare no conflict of interest.

Alzheimer's disease (AD) pathological changes may begin up to decades earlier than the appearance of the first symptoms of cognitive decline. Subjective cognitive decline (SCD) could be the first pre-clinical sign of possible AD, which might be followed by mild cognitive impairment (MCI), the initial stage of clinical cognitive decline. However, the neural correlates of these prodromic stages are not completely clear yet. Recent studies suggest that EEG analysis tools characterizing the cortical activity as a whole, such as microstates and cortical regions connectivity, might support a characterization of SCD and MCI conditions. Here we test this approach by performing a broad set of analyses to identify the prominent EEG markers differentiating SCD (n = 57), MCI (n = 46) and healthy control subjects (HC, n = 19). We found that the salient differences were in the temporal structure of the microstates patterns, with MCI being associated with less complex sequences due to the altered transition probability, frequency and duration of canonic microstate C. Spectral content of EEG, network connectivity, and spatial arrangement of microstates were instead largely similar in the three groups. Interestingly, comparing properties of EEG microstates in different cerebrospinal fluid (CSF) biomarkers profiles, we found that canonic microstate C displayed significant differences in topography in AD-like profile. These results show that the progression of dementia might be associated with a degradation of the cortical organization captured by microstates analysis, and that this leads to altered transitions between cortical states. Overall, our approach paves the way for the use of non-invasive EEG recordings in the identification of possible biomarkers of progression to AD from its prodromal states., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Patients with idiopathic normal pressure hydrocephalus (iNPH) frequently show pathologic CSF Aβ 42 levels, comparable with Alzheimer's Disease (AD). Nevertheless, the clinical meaning of these findings has not been fully explained. We aimed to assess the role of AD CSF biomarkers (Aβ 42 , Aβ 42 /Aβ 40 , p-tau, t-tau) in iNPH. To this purpose, we enrolled 44 patients diagnosed with iNPH and 101 with AD. All the patients underwent CSF sampling. We compared CSF biomarker levels in iNPH and AD: Aβ 42 levels were not different between iNPH and AD, while Aβ 42 /Aβ 40 , p-tau, and t-tau were significantly different and showed excellent accuracy in distinguishing iNPH and AD. A multiple logistic regression analysis showed that Aβ 42 /Aβ 40 was the variable that most contributed to differentiating the two groups. Furthermore, iNPH patients with positive Aβ 42 /Aβ 40 had higher p-tau and t-tau than iNPH patients with negative Aβ 42 /Aβ 40 . Those iNPH patients who showed cognitive impairment had lower Aβ 42 /Aβ 40 and higher p-tau than patients without cognitive impairment. We concluded that positive CSF Aβ 42 with negative Aβ 42 /Aβ 40 , p-tau, and t-tau is a typical CSF profile of iNPH. On the contrary, positive Aβ 42 /Aβ 40 in iNPH patients, especially when associated with positive p-tau, may lead to suspicion of a coexistent AD pathology.

Objective: HTT is a gene containing a key region of CAG repeats. When expanded beyond 39 repeats, Huntington disease (HD) develops. HTT genes with <35 repeats are not associated with HD. The biological function of CAG repeat expansion below the non-pathological threshold is not well understood. In fact higher number of repeats in HTT confer advantageous changes in brain structure and general intelligence, but several studies focused on establishing the association between CAG expansions and susceptibility to psychiatric disturbances and to other neurodegenerative disease than HD. We hypothesized that HTT CAG repeat length below the pathological threshold might influence mood and personality traits in a longitudinal sample of individuals with Subjective Cognitive Decline., Methods: We included 54 patients with SCD. All patients underwent an extensive neuropsychological battery at baseline, APOE genotyping and analysis of HTT alleles. We used the Big Five Factors Questionnaire (BFFQ) and Hamilton Depression Rating Scale (HDRS), respectively, to assess personality traits of patients and depression at baseline. Patients who did not progress to Mild Cognitive Impairment (MCI) had at least 5-year follow-up time., Results: In the whole sample, CAG repeat number in the shorter HTT allele was inversely correlated with conscientiousness (Pearson = -0.364, p = 0.007). There was no correlation between HDRS and CAG repeats. During the follow-up, 14 patients [25.93% (95% C.I. = 14.24-37.61)] progressed to MCI (MCI + ) and 40 [74.07% (95% C.I. = 62.39-85.76)] did not (MCI - ). When we performed the same analysis in the MCI + group we found that: CAG repeat length on the shorter allele was inversely correlated with energy (Pearson = 0.639, p = 0.014) and conscientiousness (Pearson = -0.695, p = 0.006). CAG repeat length on the longer allele was inversely correlated with conscientiousness (Pearson = -0.901, p < 0.001) and directly correlated with emotional stability (Pearson = 0.639, p = 0.014). These associations were confirmed also by multivariate analysis. We found no correlations between BFFQ parameters and CAG repeats in the MCI - group., Discussion: Personality traits and CAG repeat length in the intermediate range have been associated with progression of cognitive decline and neuropathological findings consistent with AD. We showed that CAG repeat lengths in the HTT gene within the non-pathological range influence personality traits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Moschini, Mazzeo, Bagnoli, Padiglioni, Emiliani, Giacomucci, Morinelli, Ingannato, Freni, Belloni, Ferrari, Sorbi, Nacmias and Bessi.)

Objective: The aim of this randomized, patient-blinded study was to compare efficacy and safety of oral paracetamol plus intra-venous (i.v.) ketorolac with i.v. ketorolac alone after ambulatory uterine evacuation., Research Design and Methods: Women were randomly assigned to receive either oral paracetamol (1 g), in a melt-in-the mouth, without-water formulation plus ketorolac (30 mg i.v. once daily (o.d.)) or ketorolac (30 mg i.v. o.d.) as monotherapy. The mean duration of uterine evacuation was 11 minutes in the paracetamol + ketorolac group and 13 minutes in the ketorolac-only group. Paracetamol was administered 15 minutes before surgery, on discharge from hospital (mean 6 hours after surgery) and in the morning the day after surgery, while ketorolac was administered at the end of the surgical intervention., Main Outcome Measures: The numeric rating scale (NRS) was used by patients to rate their pain on an 11 point scale., Results: Overall, 60 women received paracetamol plus ketorolac (group 1) and 60 ketorolac alone (group 2). There were significant differences in pain levels (NRS 0.92 and 2.08; p < 0.01) at T0 (when patients left the operating room 30 minutes after the end of surgery). At T1 (before discharge from hospital but before the next administration of paracetamol) there were no significant differences between NRS scores in the two groups (3.7 vs. 3.5, respectively, p = 0.3453). At T2 (in the morning after surgery; data collected by phone interview), following administration of the next dose of paracetamol, significant differences in pain scores were recorded (1.58 vs. 1.98; p = 0.01). Only a case of dizziness was reported in the paracetamol + ketorolac group, and no other unexpected adverse events were recorded., Conclusion: Despite the small sample size and the monocentric nature of the study being taken into account, this study suggests, for the first time to our knowledge, that oral paracetamol t.i.d. in combination with i.v. ketorolac o.d. is effective and well tolerated in the control of postoperative pain after ambulatory uterine evacuation.

Context: Neuropathic pain is common, disabling, and often difficult to treat., Objectives: To compare guideline-based drug management with Scrambler therapy, a patient-specific electrocutaneous nerve stimulation device., Methods: A clinical trial with patients randomized to either guideline-based pharmacological treatment or Scrambler therapy for a cycle of 10 daily sessions was performed. Patients were matched by type of pain including postsurgical neuropathic pain, postherpetic neuralgia, or spinal canal stenosis. Primary outcome was change in visual analogue scale (VAS) pain scores at one month; secondary outcomes included VAS pain scores at two and three months, pain medication use, and allodynia., Results: Fifty-two patients were randomized. The mean VAS pain score before treatment was 8.1 points (control) and 8.0 points (Scrambler). At one month, the mean VAS score was reduced from 8.1 to 5.8 (-28%) in the control group, and from 8 to 0.7 points (-91%) in the Scrambler group (P<0.0001). At two and three months, the mean pain scores in the control group were 5.7 and 5.9 points, respectively, and 1.4 and 2 points in the Scrambler group, respectively (P<0.0001). More relapses were seen in polyradicular pain than monoradicular pain, but retreatment and maintenance therapy gave relief. No adverse effects were observed., Conclusion: In this pilot randomized trial, Scrambler therapy appeared to relieve chronic neuropathic pain better than guideline-based drug management., (Copyright © 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Despite the large variety of equipment available for pediatric intubations, difficult tracheal intubation is still a main factor in deaths associated with anesthesia, especially in children with congenital anomalies of the airways or with rare diseases and syndromes. The aim of this study was to focus attention on the possibility of difficult intubation in children with preauricular tags. This condition is reported as both isolated and associated with more complex syndromes, including nephrourological anomalies and multiple craniofacial dysmorphysms. We retrospectively analyzed the anesthesia procedures for seven children (aged between 3 and 18 months) who underwent surgical ablation of preauricular tags between October 2006 and April 2008 at the Fondazione Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena of Milan. Two of these children, both native residents of Sri Lanka, presented with a problematic airway and difficult tracheal intubation, which was suspected in one case but totally unexpected in the other. Considering the International Guidelines for difficult intubation in pediatrics and the data of other authors, our conclusions for how to approach a child with preauricular tags are: 1) to verify whether the defect is isolated or associated with other malformations; 2) to analyze the medical history and to perform an accurate physical examination to identify a possibly difficult airway; and 3) to not exceed three attempts to intubate and, if possible, to choose an alternative strategy.

A tracheal rupture is a rare complication of tracheal intubation. Risk factors include advanced age, COBP and corticosteroid therapy. The direct causes of the rupture are difficult tracheal intubation, particularly with a stylet inside the tube and overdistension of the cuff of the tracheal tube. The case of a 73-year-old woman with a tracheal rupture after an uncomplicated operation of a vaginal hysterectomy and bilateral adenexectomy is reported. The procedure of orotracheal intubation presented no difficulties. However, after 5 h the patient was presenting unexpected symptoms such as dyspnea and subcutaneous emphysema. After an inconclusive chest X-ray and chest TC, the diagnosis was made by emergency fiberendoscopy. We adopted a conservative treatment, consisting of a tracheal intubation and chest drain, which resulted in a full recovery after 5 days of mechanical ventilation. The causes that could have provoked a tracheal laceration in our patient and the suggested therapies with preference for conservative treatment, are discussed. We recommend a tracheal tube cuff monitoring during surgery, to prevent fatal overinflation of the cuff, which is permeable to nitrous oxide.

Background: Retrospective study in patients undergoing cataract surgery by facoemulsification in order to evaluate the incidence of regional peribulbar anaesthesia compared with MAC (Monitored Anesthesia Care)., Methods: Between January 1999 and December 2000, 1902 patients were studied. Peribulbar anaesthesia was performed by using a double or single inferior-lateral injection with a mixture of Lidocaine 2% and Bupivacaine 0.5% or, as a single agent, of Ropivacaine 0.75%. Jaluronydase 10 UI/ml was added to either agents., Results: Only in 8% of patients intravenous drugs were added during surgery to correct bradycardia in 3%, hypertension 3% and for sedation in 2%., Conclusions: Regional anesthesia represents the most suitable anesthesia technique in patients undergoing cataract surgery by facoemulsification. Only in 8% of patients MAC was suitable, due to excessive anxiety or cardiovascular imbalance. Compared to other anesthesia techniques, regional anaesthesia is significantly safer. The utility of preoperative tests in reducing the morbidity associated with surgery, is also discussed.

Background: Retrospective study in pediatric patients with Cornelia de Lange syndrome undergoing different surgical operations, in order to critically evaluate the anesthesiologic aspects of this syndrome., Methods: Between January 1997 and December 1998, 42 patients undergoing diagnostic examinations (esophagogastroscopy, oculistic visit) or surgery (total exodontia, fundoplicatio for esophageal reflux, correction of labiopalatoschisis) have been studied. The anaesthesiologic technique has been similar for all the cases., Results: Any particular difficulty or inconvenience in comparison with patients with the same range of age, or particular intraoperative difficulties have been observed. In only one patient the McCoy laryngoscope was used due to difficult intubation (Cormack and Lehane III)., Conclusions: Short neck, ogive palatum, cleft palate, micrognatia, urogenital and gastroenteric anomalies, esophageal reflux, together with heart defects (15% of cases), can complicate the peri and postoperative period in these patients. A careful preoperative evaluation and a careful perioperative management, may decrease anesthetic complications in Cornelia de Lange syndrome to the same range of normal patients.

Background: Evaluation of difficulties and modalities of tracheal intubation in maxillofacial surgery., Design: retrospective study., Setting: maxillofacial operation room. 2152 patients who underwent elective maxillofacial surgery during a five-year time, from 1994 to 1998. Indications and alternative modalities of tracheal intubation through fiberoptic bronchoscope in eight patients (0.37%) with preoperatively evaluated difficult intubation due to temporomandibular ankylosis (3 patients), burns sequelae (1 patient), craniofacial congenital malformations (2 patients), unstables fractures of the cervical spine (2 patients), are discussed. Fiberoptic bronchoscope was used through nasotracheal route under topical nasal and laryngeal anaesthesia, combined with appropriate benzoanalgesia, in order to maintain spontaneous breathing. Proper positioning of tracheal tube was directly checked by fiberoptic bronchoscope, through visualization of the tracheal carina., Results: In seven patients tracheal intubation was easily performed without complications in less than 20 minutes. In the eight patients the time spent was 35 minutes, due to important nasal bleeding, which caused a change of the nostril., Conclusion: Among the alternative methods of elective tracheal intubation, previously evaluated as difficult or impossible using conventional laryngoscopy, the use of fiberoptic bronchoscope seems to be safest and easiest to use, although not the cheapest.

Background: The phantom breast syndrome (PBS) is a complication of mastectomy which consists of a sensation of breast persistence after mastectomy. MATERIALS, PATIENTS AND METHODS: The incidence, clinical course and location of PBS in 97 operated women were studied for a 15-year period. All women were interviewed in postoperative follow-up controls after mastectomy., Results: The incidence of PBS was 29 patients out of the 97 total. The syndrome was present for more than 48 months in eleven of these patients. In most cases the location of "phantom sensations" was the nipple (15 cases) and the entire breast in five patients. In only three patients was phantom breast pain (PBP) reported whereas some discomfort was reported by the other patients., Conclusions: The incidence of PBS in our series was similar to that reported by other authors, but PBP was less common. Neither postoperative sequelae nor the antitumoral specific therapy seemed to have influence on the emergence of PBS.

Hypertrophic pyloric stenosis is one of the most common gastrointestinal abnormalities occurring in the first six months of life. It is a medical emergency and surgical therapy is considered only after correction of fluid and electrolyte deficits. Careful preoperative therapy to correct deficits may require several days to ensure safe general anaesthesia and surgery. The anaesthetic management of 58 consecutive infants (51 male, 7 female) with congenital hypertrophic pyloric stenosis over a 4-year period is reviewed. Mean age was 39.5 days (range 13-100), mean weight was 3.95 kg (range 2.4-5.3). Elective Ramstadt's fibromyotomy was performed after water-electrolyte balance restoration. Inhalation induction was made and oro-tracheal intubation achieved with succinylcholine 1.5 mg/kg-1. General anaesthesia was performed without complications. All patients were discharged during the period between the 2nd and 7th day after surgery, except one who was discharged after 16 days because of dehiscence of the surgical wall. Preoperative preparation is the primary factor contributing to the low perioperative complication rates, and the necessity to recognize fluid and electrolyte imbalance is the key for a successful anaesthetic management.

Twenty patients with migraine with visual aura, aged 19 to 55 years (2 men and 18 women) were studied by the method of Visual Evoked Potentials (VEP). The control group consisted of an equal number of healthy subjects, comparable for age and sex. The most important finding in our study is that migraine patients with visual prodromata have a significantly longer P100 latency than the subjects of control group. These modifications of the VEP-PR could indicate, as other investigators have pointed out, that there are some special metabolic conditions and abnormalities of neuromediators during and between attacks.