Diagnostic criteria for small fibre neuropathy in clinical practice and research

The diagnostic criteria for small fibre neuropathy are not established, influencing the approach to patients in clinical practice, their access to disease-modifying and symptomatic treatments, the use of healthcare resources, and the design of clinical trials. To address these issues, we performed a reappraisal study of 150 patients with sensory neuropathy and a prospective and follow-up validation study of 352 new subjects with suspected sensory neuropathy. Small fibre neuropathy diagnostic criteria were based on deep clinical phenotyping, quantitative sensory testing (QST) and intraepidermal nerve fibre density (IENFD). Small fibre neuropathy was ruled out in 5 of 150 patients (3.3%) of the reappraisal study. Small fibre neuropathy was diagnosed at baseline of the validation study in 149 of 352 patients (42.4%) based on the combination between two clinical signs and abnormal QST and IENFD (69.1%), abnormal QST alone (5.4%), or abnormal IENFD alone (20.1%). Eight patients (5.4%) had abnormal QST and IENFD but no clinical signs. Further, 38 patients complained of sensory symptoms but showed no clinical signs. Of those, 34 (89.4%) had normal QST and IENFD, 4 (10.5%) had abnormal QST and normal IENFD, and none had abnormal IENFD alone. At 18-month follow-up, 19 of them (56%) reported the complete recovery of symptoms and showed normal clinical, QST and IENFD findings. None of those with one single abnormal test (QST or IENFD) developed clinical signs or showed abnormal findings on the other test. Conversely, all eight patients with abnormal QST and IENFD at baseline developed clinical signs at follow-up. The combination of clinical signs and abnormal QST and/or IENFD findings can more reliably lead to the diagnosis of small fibre neuropathy than the combination of abnormal QST and IENFD findings in the absence of clinical signs. Sensory symptoms alone should not be considered a reliable screening feature. Our findings demonstrate that the combined clinical, functional and structural approach to the diagnosis of small fibre neuropathy is reliable and relevant both for clinical practice and clinical trial design

The processing of actions and-action words in Amyotrophic Lateral Sclerosis patients

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with prime conse- quences on the motor function and concomitant cognitive changes, most frequently in the domain of executive functions. Moreover, poorer performance with action-verbs versus object-nouns has been reported in ALS patients, raising the hypothesis that the motor dysfunction deteriorates the semantic representation of actions. Using action-verbs and manipulable-object nouns sharing semantic relationship with the same motor represen- tations, the verb-noun difference was assessed in a group of 21 ALS-patients with severely impaired motor behavior, and compared with a normal sample's performance. ALS-group performed better on nouns than verbs, both in production (action and object naming) and comprehension (word-picture matching). This observation implies that the interpretation of the verb-noun difference in ALS cannot be accounted by the relatedness of verbs to motor representations, but has to consider the role of other semantic and/or morpho- phonological dimensions that distinctively define the two grammatical classes. More- over, this difference in the ALS-group was not greater than the noun-verb difference in the normal sample. The mental representation of actions also involves an executive-control component to organize, in logical/temporal order, the individual motor events (or sub- goals) that form a purposeful action. We assessed this ability with action sequencing tasks, requiring participants to re-construct a purposeful action from the scrambled pre- sentation of its constitutive motor events, shown in the form of photographs or short sentences. In those tasks, ALS-group's performance was significantly poorer than controls'. Thus, the executive dysfunction manifested in the sequencing deficit ebut not the selec- tive verb deficite appears as a consistent feature of the cognitive profile associated with LS. We suggest that ALS can offer a valuable model to study the relationship between (frontal) motor centers and the executive-control machinery housed in the frontal brain, and the implications of executive dysfunctions in tasks such as action processing

efficacy of botulinum toxin type a treatment of functional impairment of degenerative hip joint preliminary results

Objective: the aim of this study was to investigate the effect of botulinum toxin type a injection into the adductor muscles in reducing pain and improving joint mobility and quality of life in patients affected by hip osteoarthritis. Methods: a total of 39 outpatients, mean age 68 years (age range 41–82 years), were evaluated using the harris hip Score to test hip function, a visual analogue scale to measure pain intensity and the Short Form 36 (SF-36) questionnaire to assess patient well-being and quality of life at baseline, 2, 4 and 12 weeks after treatment with botulinum toxin type a. a total of 400 u of botulinum toxin type a (Dysport) was injected into the adductor longus muscle and the adductor magnus muscle. Results: The Harris Hip Score increased significantly after 2, 4 and 12 weeks (df 3, χ 2 = 45.1; p < 0.0001). A significant decrease in pain intensity was detected at all the follow-up visits, after 2, 4 and 12 weeks (df 3; χ 2 = 27.8; p < 0.001). the SF-36 score was significantly higher 4 and 12 weeks after treatment. At each evaluation visit a significant correlation was detected between decreased pain and improved hip mobility. Conclusion: Botulinum toxin type a induced a reduction in pain, indicating that this might be an innovative, less invasive treatment in patients affected by severe hip osteoarthritis, with remarkable effects on the clinical management of this disease

Efficacy of botulinum toxin type A treatment of functional impairment of degenerative hip joint: Preliminary results

Objective: the aim of this study was to investigate the effect of botulinum toxin type a injection into the adductor muscles in reducing pain and improving joint mobility and quality of life in patients affected by hip osteoarthritis. Methods: a total of 39 outpatients, mean age 68 years (age range 41–82 years), were evaluated using the harris hip Score to test hip function, a visual analogue scale to measure pain intensity and the Short Form 36 (SF-36) questionnaire to assess patient well-being and quality of life at baseline, 2, 4 and 12 weeks after treatment with botulinum toxin type a. a total of 400 u of botulinum toxin type a (Dysport) was injected into the adductor longus muscle and the adductor magnus muscle. Results: The Harris Hip Score increased significantly after 2, 4 and 12 weeks (df 3, χ 2 = 45.1; p < 0.0001). A significant decrease in pain intensity was detected at all the follow-up visits, after 2, 4 and 12 weeks (df 3; χ 2 = 27.8; p < 0.001). the SF-36 score was significantly higher 4 and 12 weeks after treatment. At each evaluation visit a significant correlation was detected between decreased pain and improved hip mobility. Conclusion: Botulinum toxin type a induced a reduction in pain, indicating that this might be an innovative, less invasive treatment in patients affected by severe hip osteoarthritis, with remarkable effects on the clinical management of this disease

Second Surgery in Insular Low-Grade Gliomas

Background. Given the technical difficulties, a limited number of works have been published on insular gliomas surgery and risk factors for tumor recurrence (TR) are poorly documented. Objective. The aim of the study was to determine TR in adult patients with initial diagnosis of insular Low-Grade Gliomas (LGGs) that subsequently underwent second surgery. Methods. A consecutive series of 53 patients with insular LGGs was retrospectively reviewed; 23 patients had two operations for TR. Results. At the time of second surgery, almost half of the patients had experienced progression into high-grade gliomas (HGGs). Univariate analysis showed that TR is influenced by the following: extent of resection (EOR) (P &lt; 0.002),.VT2T1 value (P &lt; 0.001), histological diagnosis of oligodendroglioma (P = 0.017), and mutation of IDH1 (P = 0.022). The multivariate analysis showed that EOR at first surgery was the independent predictor for TR (P] &lt; 0.001). Conclusions. In patients with insular LGG the EOR at first surgery represents the major predictive factor for TR. At time of TR, more than 50% of cases had progressed in HGG, raising the question of the oncological management after the first surgery

Patient-Reported Side Effects of Intradetrusor Botulinum Toxin Type A for Idiopathic Overactive Bladder Syndrome

Objective: The aim of the study was a prospective assessment of patient-reported side effects in an open-label study after intradetrusor botulinum toxin injections for idiopathic overactive bladder (OAB). Patients and Methods: Botulinum toxin A injection was performed in 56 patients with idiopathic OAB. Patients were followed up for 6 months concerning side effects and patients' satisfaction. Results: Different types of side effects were assessed such as dry mouth (19.6%), arm weakness (8.9%), eyelid weakness (8.9%), leg weakness (7.1%), torso weakness (5.4%), impaired vision (5.4%) and dysphagia (5.4%). In all cases, symptoms were mild and transient. Urological complications such as gross hematuria (17.9%), acute urinary retention (8.9%) and acute urinary tract infection (7.1%) were noticed. In all cases, acute urinary retention was transient and treated with temporary intermittent self-catheterization. There was no statistically significant correlation between dosage and observed side effects. Patients' satisfaction rate was high (71.4%). Conclusion: Intradetrusor injection of botulinum toxin was associated with a high rate of neurourological side effects. In general, side effects were transient, mild and did not require special treatment. Copyright (C) 2010 S. Karger AG, Base

The alpha-synuclein RT-QuIC products generated by the olfactory mucosa of patients with parkinson’s disease and multiple system atrophy induce inflammatory responses in SH-SY5Y cells

Parkinson’s disease (PD) and multiple system atrophy (MSA) are caused by two distinct strains of disease-associated α-synuclein (αSynD). Recently, we have shown that olfactory mucosa (OM) samples of patients with PD and MSA can seed the aggregation of recombinant α-synuclein by means of Real-Time Quaking-Induced Conversion (αSyn_RT-QuIC). Remarkably, the biochemical and morphological properties of the final α-synuclein aggregates significantly differed between PD and MSA seeded samples. Here, these aggregates were given to neuron-like differentiated SH-SY5Y cells and distinct inflammatory responses were observed. To deepen whether the morphological features of α-synuclein aggregates were responsible for this variable SH-SY5Y inflammatory response, we generated three biochemically and morphologically distinct α-synuclein aggregates starting from recombinant α-synuclein that were used to seed αSyn_RT-QuIC reaction; the final reaction products were used to stimulate SH-SY5Y cells. Our study showed that, in contrast to OM samples of PD and MSA patients, the artificial aggregates did not transfer their distinctive features to the αSyn_RT-QuIC products and the latter induced analogous inflammatory responses in cells. Thus, the natural composition of the αSynD strains but also other specific factors in OM tissue can substantially modulate the biochemical, morphological and inflammatory features of the αSyn_RT-QuIC products

Multiple system atrophy is distinguished from idiopathic Parkinson's disease bythe arginine growth hormone stimulation test

Objective: Multiple system atrophy (MSA) may be difficult to distinguish from idiopathic Parkinson’s disease (PD). Our aim was to evaluate the accuracy of the arginine growth hormone (GH) stimulation test in distinguishing between MSA and PD in large populations of patients. Methods: We measured the GH response to arginine in 69 MSA (43 MSAp [parkinsonism as the main motor feature] and 26 MSAc [cerebellar features predominated]) patients, 35 PD patients, and 90 healthy control subjects. We used receiver-operating curve analysis to establish the arginine cutoff value that best differentiated between MSA and PD. Results: The GH response to arginine was significantly lower (p 0.01) in MSA than in either PD patients or control subjects. At a cutoff level of 4g/L, arginine distinguished MSAp from PD with a sensitivity and specificity of 91% and MSAc from PD with a sensitivity of 96% and specificity of 91%. The arginine test had a positive predictive value for MSA of 95%. The GH response to arginine was not affected by disease duration or severity, MSA motor subtype, pyramidal signs, response to dopaminergic therapy, or magnetic resonance imaging findings. Interpretation: The GH response to arginine differentiates MSA from PD with a high diagnostic accuracy. The results suggest an impairment of cholinergic central systems modulating GH release in MSA

Linee guida per la diagnosi, il trattamento e il supporto dei pazienti affetti da demenza

Il termine demenza descrive una serie di sintomi cognitivi, comportamentali e psicologici che possono includere perdita di memoria, difficoltà di ragionamento e di comunicazione e cambiamenti della personalità che compromettono la capacità di svolgere le attività quotidiane. Nel 2013 un rapporto della Alzheimer’s Society ha rilevato che nel Regno Unito erano circa 815.000 le persone affette da demenza (prevalenza 1/14 abitanti di età >65 anni), un numero destinato ad aumentare sino a 1.143.000 entro il 2025. Nel novembre 2017 erano 456.739 i pazienti con una diagnosi certa di demenza nei registri di medicina generale, rispetto ai 290.000 del periodo 2009-2010, la differenza in gran parte imputabile ad un aumento del numero di diagnosi. Nonostante questo miglioramento nella diagnosi della demenza, si stima che circa 1 caso su 3 non venga riconosciuto correttamente; inoltre, circa la metà delle persone affette da demenza non riceve un adeguato supporto dopo la diagnosi. Questo articolo riassume le raccomandazioni più recenti del National Institute for Health and Care Excellence (NICE) per la valutazione, la gestione e il supporto delle persone affette da demenza e dei loro caregiver. La linea guida (LG) aggiorna e sostituisce integralmente la LG NICE sulla demenza del 2006. Raccomandazioni, dettagli completi delle evidenze e il PDTA sono disponibili sul sito del NICE. Le raccomandazioni del NICE sono basate su revisioni sistematiche delle migliori evidenze disponibili e su una esplicita considerazione della costo-efficacia. Quando le evidenze disponibili sono limitate, le raccomandazioni sono basate sull’esperienza del gruppo che ha prodotto la linea guida – Guideline Development Group’s (GDG) – e sulle norme di buona pratica clinica. I livelli di evidenza delle raccomandazioni cliniche sono indicati in corsivo tra parentesi quadre