Filippo Maria Cogiamanian
@policlinico.mi.it
Neuropathophysiology Unit
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
RESEARCH INTERESTS
Deep Brain Stimulation in Parkinson disease
Scopus Publications
Scopus Publications
Luigi Gianmaria Remore, Leonardo Tariciotti, Giorgio Fiore, Elena Pirola, Linda Borellini, Filippo Cogiamanian, Antonella Maria Ampollini, Luigi Schisano, Dario Gagliano, Stefano Borsa,et al.
Elsevier BV
Marco Percetti, Michela Zini, Paola Soliveri, Filippo Cogiamanian, Mariarosa Ferrara, Eva Orunesu, Alessandra Ranghetti, Carlo Ferrarese, Gianni Pezzoli, Barbara Garavaglia,et al.
Wiley
AbstractBackgroundMutations in ANO3 are a rare cause of autosomal dominant isolated or combined dystonia, mainly presenting in adulthood.CasesWe extensively characterize a new, large ANO3 family with six affected carriers. The proband is a young girl who had suffered from tremor and painful dystonic movements in her right arm since the age of 11 years. She later developed a diffuse dystonic tremor and mild extrapyramidal signs (ie, rigidity and hypodiadochokinesis) in her right arm. She also suffered from psychomotor delay and learning difficulties. Repeated structural and functional neuroimaging were unremarkable. A dystonic tremor was also present in her two sisters. Her paternal aunt, father, and a third older sister presented episodic postural tremor in the arms. The father and one sister also presented learning difficulties. The heterozygous p.G6V variant in ANO3 was identified in all affected subjects.Literature reviewStratification by age at onset divided ANO3 cases into two major groups, where younger patients displayed a more severe phenotype, probably due to variants near the scrambling domain.ConclusionsWe describe the phenotype of a new ANO3 family and highlight the need for functional studies to explore the impact of ANO3 variants on its phospholipid scrambling activity.
Francesca Mameli, Fabiana Ruggiero, Michelangelo Dini, Sara Marceglia, Marco Prenassi, Linda Borellini, Filippo Cogiamanian, Elena Pirola, Luigi Gianmaria Remore, Giorgio Fiore,et al.
Elsevier BV
Micol Avenali, Roberta Zangaglia, Giada Cuconato, Ilaria Palmieri, Alberto Albanese, Carlo Alberto Artusi, Marco Bozzali, Giovanna Calandra-Buonaura, Francesco Cavallieri, Roberto Cilia,et al.
BMJ
BackgroundGBAvariants increase the risk of developing Parkinson disease (PD) and influence its outcome. Deep brain stimulation (DBS) is a recognised therapeutic option for advanced PD. Data on DBS long-term outcome inGBAcarriers are scarce.ObjectiveTo elucidate the impact ofGBAvariants on long-term DBS outcome in a large Italian cohort.MethodsWe retrospectively recruited a multicentric Italian DBS-PD cohort and assessed: (1)GBAprevalence; (2) pre-DBS clinical features; and (3) outcomes of motor, cognitive and other non-motor features up to 5 years post-DBS.ResultsWe included 365 patients with PD, of whom 73 (20%) carriedGBAvariants. 5-year follow-up data were available for 173 PD, including 32 mutated subjects. GBA-PD had an earlier onset and were younger at DBS than non-GBA-PD. They also had shorter disease duration, higher occurrence of dyskinesias and orthostatic hypotension symptoms.At post-DBS, both groups showed marked motor improvement, a significant reduction of fluctuations, dyskinesias and impulsive-compulsive disorders (ICD) and low occurrence of most complications. Only cognitive scores worsened significantly faster in GBA-PD after 3 years. Overt dementia was diagnosed in 11% non-GBA-PD and 25% GBA-PD at 5-year follow-up.ConclusionsEvaluation of long-term impact ofGBAvariants in a large Italian DBS-PD cohort supported the role of DBS surgery as a valid therapeutic strategy in GBA-PD, with long-term benefit on motor performance and ICD. Despite the selective worsening of cognitive scores since 3 years post-DBS, the majority of GBA-PD had not developed dementia at 5-year follow-up.
Daniele Velardo, Sara Antognozzi, Martina Rimoldi, Serena Pagliarani, Filippo Cogiamanian, Sergio Barbieri, Stefania Corti, Giacomo Pietro Comi, and Dario Ronchi
Frontiers Media SA
Exercise-induced muscle stiffness is the hallmark of Brody disease, an autosomal recessive myopathy due to biallelic pathogenic variants in ATP2A1, encoding the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase SERCA1. About 40 patients have been reported so far. Our knowledge about the natural history of this disorder, genotype–phenotype correlations and the effect of symptomatic treatment is partial. This results in incomplete recognition and underdiagnosis of the disease. Here, we report the clinical, instrumental, and molecular features of two siblings presenting childhood-onset exercise-induced muscle stiffness without pain. Both the probands display difficulty in climbing stairs and running, frequent falls, delayed muscle relaxation after exertion. Cold temperatures worsen these symptoms. No myotonic discharges were observed at electromyography. Whole Exome Sequencing analysis in the probands revealed the presence of two ATP2A1 variants: the previously reported frameshift microdeletion c.2464delC and the likely pathogenic novel splice-site variant c.324 + 1G > A, whose detrimental effect was demonstrated in ATP2A1 transcript analysis. The bi-allelic inheritance was verified by Sanger sequencing in the unaffected parents. This study expands the molecular defects associated with Brody myopathy.
Tommaso Bocci, Marco Prenassi, Mattia Arlotti, Filippo Maria Cogiamanian, Linda Borellini, Elena Moro, Andres M. Lozano, Jens Volkmann, Sergio Barbieri, Alberto Priori,et al.
Springer Science and Business Media LLC
Giorgio Fiore, Giorgia Abete-Fornara, Arianna Forgione, Leonardo Tariciotti, Mauro Pluderi, Stefano Borsa, Cristina Bana, Filippo Cogiamanian, Maurizio Vergari, Valeria Conte,et al.
Frontiers Media SA
BackgroundAwake surgery (AS) permits intraoperative mapping of cognitive and motor functions, allowing neurosurgeons to tailor the resection according to patient functional boundaries thus preserving long-term patient integrity and maximizing extent of resection. Given the increased risks of the awake scenario, the growing importance of AS in surgical practice favored the debate about patient selection concerning both indication and eligibility criteria. Nonetheless, a systematic investigation is lacking in the literature.ObjectiveTo provide a scoping review of the literature concerning indication and eligibility criteria for AS in patients with gliomas to answer the questions:1) "What are the functions mostly tested during AS protocols?" and 2) "When and why should a patient be excluded from AS?".Materials and methodsPertinent studies were retrieved from PubMed, PsycArticles and Cochrane Central Register of Controlled Trials (CENTRAL), published until April 2021 according to the PRISMA Statement Extension for Scoping Reviews. The retrieved abstracts were checked for the following features being clearly stated: 1) the population described as being composed of glioma(LGG or HGG) patients; 2) the paper had to declare which cognitive or sensorimotor function was tested, or 2bis)the decisional process of inclusion/exclusion for AS had to be described from at least one of the following perspectives: neurosurgical, neurophysiological, anesthesiologic and psychological/neuropsychological.ResultsOne hundred and seventy-eight studies stated the functions being tested on 8004 patients. Language is the main indication for AS, even if tasks and stimulation techniques changed over the years. It is followed by monitoring of sensorimotor and visuospatial pathways. This review demonstrated an increasing interest in addressing other superior cognitive functions, such as executive functions and emotions. Forty-five studies on 2645 glioma patients stated the inclusion/exclusion criteria for AS eligibility. Inability to cooperate due to psychological disorder(i.e. anxiety),severe language deficits and other medical conditions(i.e.cardiovascular diseases, obesity, etc.)are widely reported as exclusion criteria for AS. However, a very few papers gave scale exact cut-off. Likewise, age and tumor histology are not standardized parameters for patient selection.ConclusionGiven the broad spectrum of functions that might be safely and effectively monitored via AS, neurosurgeons and their teams should tailor intraoperative testing on patient needs and background as well as on tumor location and features. Whenever the aforementioned exclusion criteria are not fulfilled, AS should be strongly considered for glioma patients.
Marco Prenassi, Linda Borellini, Tommaso Bocci, Elisa Scola, Sergio Barbieri, Alberto Priori, Roberta Ferrucci, Filippo Cogiamanian, Marco Locatelli, Paolo Rampini,et al.
Frontiers Media SA
Implanting deep brain stimulation (DBS) electrodes in patients with Parkinson’s disease often results in the appearance of a non-infectious, delayed-onset edema that disappears over time. However, the time window between the DBS electrode and DBS stimulating device implant is often used to record local field potentials (LFPs) which are used both to better understand basal ganglia pathophysiology and to improve DBS therapy. In this work, we investigated whether the presence of post-surgery edema correlates with the quality of LFP recordings in eight patients with advanced Parkinson’s disease implanted with subthalamic DBS electrodes. The magnetic resonance scans of the brain after 8.5 ± 1.5 days from the implantation surgery were segmented and the peri-electrode edema volume was calculated for both brain hemispheres. We found a correlation (ρ = −0.81, p < 0.0218, Spearman’s correlation coefficient) between left side local field potentials of the low beta band (11–20 Hz) and the edema volume of the same side. No other significant differences between the hemispheres were found. Despite the limited sample size, our results suggest that the effect on LFPs may be related to the edema localization, thus indicating a mechanism involving brain networks instead of a simple change in the electrode-tissue interface.
Tommaso Bocci, Marco Prenassi, Mattia Arlotti, Filippo Maria Cogiamanian, Linda Borrellini, Elena Moro, Andres M. Lozano, Jens Volkmann, Sergio Barbieri, Alberto Priori,et al.
Springer Science and Business Media LLC
AbstractThis study compares the effects on motor symptoms between conventional deep brain stimulation (cDBS) and closed-loop adaptive deep brain stimulation (aDBS) in patients with Parkinson’s Disease. The aDBS stimulation is controlled by the power in the beta band (12–35 Hz) of local field potentials recorded directly by subthalamic nucleus electrodes. Eight subjects were assessed in two 8-h stimulation sessions (first day, cDBS; second day, aDBS) with regular levodopa intake and during normal daily activities. The Unified Parkinson’s Disease Rating Scale (UPDRS) part III scores, the Rush scale for dyskinesias, and the total electrical energy delivered to the tissues per second (TEEDs) were significantly lower in the aDBS session (relative UPDRS mean, cDBS: 0.46 ± 0.05, aDBS: 0.33 ± 0.04, p = 0.015; UPDRS part III rigidity subset mean, cDBS: 2.9143 ± 0.6551 and aDBS: 2.1429 ± 0.5010, p = 0.034; UPDRS part III standard deviation cDBS: 2.95, aDBS: 2.68; p = 0.047; Rush scale, cDBS 2.79 ± 0.39 versus aDBS 1.57 ± 0.23, p = 0.037; cDBS TEEDs mean: 28.75 ± 3.36 µj s−1, aDBS TEEDs mean: 16.47 ± 3.33, p = 0.032 Wilcoxon’s sign rank test). This work further supports the safety and effectiveness of aDBS stimulation compared to cDBS in a daily session, both in terms of motor performance and TEED to the patient.
Davide Villa, Gianluca Ardolino, Linda Borellini, Filippo Cogiamanian, Maurizio Vergari, Valeria Savojardo, Flora Peyvandi, and Sergio Barbieri
Springer Science and Business Media LLC
Coronavirus disease 2019 (COVID-19) is associated to neuromuscular symptoms in up to 10.7% of hospitalized patients. Nevertheless, the extent of muscular involvement in infected subjects with no signs of myopathy has never been assessed with neurophysiological investigations. Over a 3-week period — from April 30 through May 20, 2020 — a total of 70 patients were hospitalized in the Internal Medicine Ward of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan, Italy. After excluding patients who underwent invasive ventilation and steroid treatment, 12 patients were evaluated. Nerve conduction studies (NCS) included the analysis of conduction velocity, amplitude, and latency for bilateral motor tibial, ulnar nerves, and sensory sural and radial nerves. Unilateral concentric-needle electromyography (EMG) was performed evaluating at least 4 areas of 8 selected muscles. For each muscle, spontaneous activity at rest, morphology, and recruitment of motor unit action potentials (MUAPs) were evaluated. While nerve conduction studies were unremarkable, needle electromyography showed myopathic changes in 6 out of 12 subjects. All patients were asymptomatic for muscular involvement. Clinical features and laboratory findings did not show relevant differences between patients with and without myopathic changes. Our data show that in SARS-CoV-2 infection muscular involvement can occur despite the absence of clinical signs or symptoms and should be considered part of the disease spectrum. The application of muscle biopsy to unravel the mechanisms of myofiber damage on tissue specimens could help to clarify the pathogenesis and the treatment response of coronavirus-mediated injury.
Marco Prenassi, Mattia Arlotti, Linda Borellini, Tommaso Bocci, Filippo Cogiamanian, Marco Locatelli, Paolo Rampini, Sergio Barbieri, Alberto Priori, and Sara Marceglia
Frontiers Media SA
Background: Adaptive Deep Brain Stimulation (aDBS) is now considered as a new feasible and effective paradigm to deliver DBS to patients with Parkinson's disease (PD) in such a way that not only stimulation is personalized and finely tuned to the instantaneous patient's state, but also motor improvement is obtained with a lower amount of energy transferred to the tissue. Amplitude-controlled aDBS was shown to significantly decrease the amplitude-driven total electrical energy delivered to the tissue (aTEED), an objective measure of the amount of energy transferred by DBS amplitude to the patient's brain. However, there is no direct evidence of a relationship between aTEED and the occurrence of DBS-related adverse events in humans.Objective: In this work, we investigated the correlation of aTEED with the occurrence of levodopa-induced dyskinesias pooling all the data available from our previous experiments using aDBS and cDBS.Methods: We retrospectively analyzed data coming from 19 patients with PD undergoing surgery for STN-DBS electrode positioning and participating to experiments involving cDBS and aDBS delivery. Patients were all studied some days after the surgery (acute setting). The aTEED and dyskinesia assessments (Rush Dyskinesia Rating Scale, RDRS) considered in the Med ON-Stim ON condition.Results: We confirmed both that aTEED values and RDRS were significantly lower in the aDBS than in cDBS sessions (aTEED mean value, cDBS: 0.0278 ± 0.0011 j, vs. aDBS: 0.0071 ± 0.0003 j, p < 0.0001 Wilcoxon's rank sum; normalized RDRS mean score, cDBS: 0.66 ± 0.017 vs. aDBS: 0.45 ± 0.01, p = 0.025, Wilcoxon's rank sum test). In addition, we found a direct significant correlation between aTEED and RDRS (ρ = 0.44, p = 0.0032, Spearman's correlation).Conclusions: Our results provide a first piece of evidence that aTEED is correlated to the amount of levodopa-induced dyskinesias in patients with PD undergoing STN-DBS, thus supporting the role of aDBS as feasible and safe alternative to cDBS.
Eleonora Maggioni, Federica Arienti, Stella Minella, Francesca Mameli, Linda Borellini, Martina Nigro, Filippo Cogiamanian, Anna Maria Bianchi, Sergio Cerutti, Sergio Barbieri,et al.
Frontiers Media SA
Music-based interventions seem to enhance motor, sensory and cognitive functions in Parkinson’s disease (PD), but the underlying action mechanisms are still largely unknown. This electroencephalography (EEG) study aimed to investigate the effective connectivity patterns characterizing PD in the resting state and during music listening. EEG recordings were obtained from fourteen non-demented PD patients and 12 healthy controls, at rest and while listening to three music tracks. Theta- and alpha-band power spectral density and multivariate partial directed coherence were computed. Power and connectivity measures were compared between patients and controls in the four conditions and in music vs. rest. Compared to controls, patients showed enhanced theta-band power and slightly enhanced alpha-band power, but markedly reduced theta- and alpha-band interactions among EEG channels, especially concerning the information received by the right central channel. EEG power differences were partially reduced by music listening, which induced power increases in controls but not in patients. Connectivity differences were slightly compensated by music, whose effects largely depended on the track. In PD, music enhanced the frontotemporal inter-hemispheric communication. Our findings suggest that PD is characterized by enhanced activity but reduced information flow within the EEG network, being only partially normalized by music. Nevertheless, music capability to facilitate inter-hemispheric communication might underlie its beneficial effects on PD pathophysiology and should be further investigated.
Edoardo Monfrini, Filippo Cogiamanian, Sabrina Salani, Letizia Straniero, Gigliola Fagiolari, Manuela Garbellini, Emma Carsana, Linda Borellini, Fabio Biella, Maurizio Moggio,et al.
Wiley
In this work, we describe the association of a novel homozygous VPS11 variant with adult‐onset generalized dystonia, providing a detailed clinical report and biological evidence of disease mechanism. Vps11 is a subunit of the homotypic fusion and protein sorting (HOPS) complex, which promotes the fusion of late endosomes and autophagosomes with the lysosome. Functional studies on mutated fibroblasts showed marked lysosomal and autophagic abnormalities, which improved after overexpression of the wild type Vps11 protein. In conclusion, a deleterious VPS11 variant, damaging the autophagic and lysosomal pathways, is the probable genetic cause of a novel form of generalized dystonia. ANN NEUROL 2021;89:834–839
Linda Borellini, Filippo Cogiamanian, and Gianluca Ardolino
Elsevier BV
Gianluca Ardolino, Tommaso Bocci, Martina Nigro, Maurizio Vergari, Alessio Di Fonzo, Sara Bonato, Filippo Cogiamanian, Francesca Cortese, Ilaria Cova, Sergio Barbieri,et al.
Informa UK Limited
Objective: Hereditary spastic paraplegia (HSP) represents a heterogeneous group of neurodegenerative diseases characterized by progressive spasticity and lower limb weakness. We assessed the effects of transcutaneous spinal direct current stimulation (tsDCS) in HSP. Design: A double-blind, randomized, crossover and sham-controlled study. Setting: Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan. Participants: eleven patients with HSP (six men, mean age ± SD: 37.3 ± 8.1 years), eight affected by spastin/SPG4,1 by atlastin1/SPG3a, 1 by paraplegin/SPG7 and 1 by ZFYVE26/SPG15. Interventions: tsDCS (anodal or sham, 2.0 mA, 20’, five days) delivered over the thoracic spinal cord (T10-T12). Outcome measures: Motor-evoked potentials (MEPs), the H-reflex (Hr), F-waves, the Ashworth scale for clinical spasticity, the Five Minutes Walking test and the Spastic Paraplegia Rating Scale (SPRS) were assessed. Patients were evaluated before tsDCS (T 0), at the end of the stimulation (T 1), after one week (T 2), one month (T 3) and two months (T 4). Results: The score of the Ashworth scale improved in the anodal compared with sham group, up to two months following the end of stimulation (T1, P = .0137; T4, P = .0244), whereas the Five Minutes Walking test and SPRS did not differ between the two groups. Among neurophysiological measures, both anodal and sham tsDCS left Hr, F-waves and MEPs unchanged over time. Conclusions: Anodal tsDCS significantly decreases spasticity and might be a complementary strategy for the treatment of spasticity in HSP.
Simona Petrucci, Monia Ginevrino, Ilaria Trezzi, Edoardo Monfrini, Lucia Ricciardi, Alberto Albanese, Micol Avenali, Paolo Barone, Anna Rita Bentivoglio, Vincenzo Bonifati,et al.
Wiley
Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear.
Margherita Fabbri, Maurizio Zibetti, Mario Giorgio Rizzone, Giulia Giannini, Linda Borellini, Alessandro Stefani, Francesco Bove, Andrea Bruno, Giovanna Calandra‐Buonaura, Nicola Modugno,et al.
Wiley
Subthalamic deep brain stimulation (STN‐DBS) effects may decrease with Parkinson's disease (PD) progression. There is no indication if, when, and how to consider the interruption of DBS treatment in late‐stage PD. The objective of the current study was to investigate the percentage of “poor stimulation responders” among late‐stage PD patients for elaborating an algorithm to decide whether and when DBS discontinuation may be considered.
Barbara Zarino, Andrea Di Cristofori, Giorgia Abete Fornara, Giulio Andrea Bertani, Marco Locatelli, Manuela Caroli, Paolo Rampini, Filippo Cogiamanian, Davide Crepaldi, and Giorgio Carrabba
Springer Science and Business Media LLC
Background Patients affected by a high-grade glioma (HGG) have a poor prognosis with a median survival of 12–16 months. Such poor prognosis affects the perception of the remaining life by patients and the neuropsychological status can strongly affect every-day functioning of these patients. Monitoring changes of neuropsychological functioning (NPF) overtime may provide better clinical information and optimize the neuro-oncological management. The aims of our work were (1) to investigate the feasibility of a complex neuropsychological battery in HGG patients before and during follow-up after surgery; (2) to study the neuropsychological profile of patients affected by HGGs and their relation with the disease status (relapse/death) across time after surgery. Methods One hundred two patients who received surgery for HGG between 2011 and 2017 were studied. All clinical data were prospectively recorded. NPF was assessed during the neuro-oncological follow-up through the Milano-Bicocca Battery (MIBIB). Statistical analysis was performed on the neuropsychological results of the tests administered. Results First, MIBIB proved to be suitable for patients with HGG tumors before and after surgery, and during long-term follow-up; it also showed a cluster structure representative of the principal cognitive domains. Second, we found a steep decline in the neuropsychological profile before death and/or tumor relapse for the 52% of the neuropsychological tests administered. Conclusion Complex neuropsychological batteries can be administered to HGG patients before and during follow-up after surgery. There is a correlation between neuropsychological deterioration and tumor relapse and/or death, which may reflect a progressive damage to cognitive functions due to tumor infiltration and progression.
L. Borellini, G. Ardolino, G. Carrabba, M. Locatelli, P. Rampini, S. Sbaraini, E. Scola, S. Avignone, F. Triulzi, S. Barbieri,et al.
Wiley
The aim of this study was to define the prevalence and characteristics of peri‐electrode edema in a prospective cohort of patients undergoing deep brain stimulation (DBS) surgery and to correlate it with clinical findings.
Roberta Brusa, Irene Faravelli, Delia Gagliardi, Francesca Magri, Filippo Cogiamanian, Domenica Saccomanno, Claudia Cinnante, Eleonora Mauri, Elena Abati, Nereo Bresolin,et al.
Frontiers Media SA
Here, we describe a 79-year-old man, admitted to our unit for worsening diplopia and fatigue, started a few weeks after an episode of bronchitis and flu vaccination. Past medical history includes myasthenia gravis (MG), well-controlled by Pyridostigmine, Azathioprine, and Prednisone. During the first days, the patient developed progressive ocular movement abnormalities up to complete external ophthalmoplegia, severe limb and gait ataxia, and mild dysarthria. Deep tendon reflexes were absent in lower limbs. Since not all the symptoms were explainable with the previous diagnosis of myasthenia gravis, other etiologies were investigated. Brain MRI and cerebrospinal fluid analysis were normal. Electromyography showed a pattern of predominantly sensory multiple radiculoneuritis. Suspecting Miller Fisher syndrome (MFS), the patient was treated with plasmapheresis with subsequent clinical improvement. Antibodies against GQ1b turned out to be positive. MFS is an immune-mediated neuropathy presenting with ophthalmoplegia, ataxia, and areflexia. Even if only a few cases of MFS overlapping with MG have been described so far, the coexistence of two different autoimmune disorders can occur. It is always important to evaluate possible differential diagnosis even in case of known compatible diseases, especially when some clinical features seem atypical.
Giacomo Monzio Compagnoni, Giulio Kleiner, Andreina Bordoni, Francesco Fortunato, Dario Ronchi, Sabrina Salani, Marianna Guida, Corrado Corti, Irene Pichler, Christian Bergamini,et al.
Elsevier BV
Multiple System Atrophy is a severe neurodegenerative disorder which is characterized by a variable clinical presentation and a broad neuropathological spectrum. The pathogenic mechanisms are almost completely unknown. In the present study, we established a cellular model of MSA by using fibroblasts' primary cultures and performed several experiments to investigate the causative mechanisms of the disease, with a particular focus on mitochondrial functioning. Fibroblasts' analyses (7 MSA-P, 7 MSA-C and 6 healthy controls) displayed several anomalies in patients: an impairment of respiratory chain activity, in particular for succinate Coenzyme Q reductase (p < 0.05), and a reduction of complex II steady-state level (p < 0.01); a reduction of Coenzyme Q10 level (p < 0.001) and an up-regulation of some CoQ10 biosynthesis enzymes, namely COQ5 and COQ7; an impairment of mitophagy, demonstrated by a decreased reduction of mitochondrial markers after mitochondrial inner membrane depolarization (p < 0.05); a reduced basal autophagic activity, shown by a decreased level of LC3 II (p < 0.05); an increased mitochondrial mass in MSA-C, demonstrated by higher TOMM20 levels (p < 0.05) and suggested by a wide analysis of mitochondrial DNA content in blood of large cohorts of patients. The present study contributes to understand the causative mechanisms of Multiple System Atrophy. In particular, the observed impairment of respiratory chain activity, mitophagy and Coenzyme Q10 biosynthesis suggests that mitochondrial dysfunction plays a crucial role in the pathogenesis of the disease. Furthermore, these findings will hopefully contribute to identify novel therapeutic targets for this still incurable disorder.
Mattia Arlotti, Sara Marceglia, Guglielmo Foffani, Jens Volkmann, Andres M. Lozano, Elena Moro, Filippo Cogiamanian, Marco Prenassi, Tommaso Bocci, Francesca Cortese,et al.
Ovid Technologies (Wolters Kluwer Health)
ObjectivesTo assess the feasibility and clinical efficacy of local field potentials (LFPs)–based adaptive deep brain stimulation (aDBS) in patients with advanced Parkinson disease (PD) during daily activities in an open-label, nonblinded study.MethodsWe monitored neurophysiologic and clinical fluctuations during 2 perioperative experimental sessions lasting for up to 8 hours. On the first day, the patient took his/her daily medication, while on the second, he/she additionally underwent subthalamic nucleus aDBS driven by LFPs beta band power.ResultsThe beta band power correlated in both experimental sessions with the patient's clinical state (Pearson correlation coefficient r = 0.506, p < 0.001, and r = 0.477, p < 0.001). aDBS after LFP changes was effective (30% improvement without medication [3-way analysis of variance, interaction day × medication p = 0.036; 30.5 ± 3.4 vs 22.2 ± 3.3, p = 0.003]), safe, and well tolerated in patients performing regular daily activities and taking additional dopaminergic medication. aDBS was able to decrease DBS amplitude during motor “on” states compared to “off” states (paired t test p = 0.046), and this automatic adjustment of STN-DBS prevented dyskinesias.ConclusionsThe main findings of our study are that aDBS is technically feasible in everyday life and provides a safe, well-tolerated, and effective treatment method for the management of clinical fluctuations.Classification of evidenceThis study provides Class IV evidence that for patients with advanced PD, aDBS is safe, well tolerated, and effective in controlling PD motor symptoms.
F Bianchi
CIC Edizioni Internazionali
Neurophysiological testing of the pelvic floor is recognized as an essential tool to identify pathophysiological mechanisms of pelvic floor disorders, support clinical diagnosis, and aid in therapeutic decisions. Nevertheless, the diagnostic value of these tests in specific neurological diseases of the pelvic floor is not completely clarified. Seeking to fill this gap, the members of the Neurophysiology of the Pelvic Floor Study Group of the Italian Clinical Neurophysiology Society performed a systematic review of the literature to gather available evidence for and against the utility of neurophysiological tests. Our findings confirm the utility of some tests in specific clinical conditions [e.g. concentric needle electromyography, evaluation of sacral reflexes and of pudendal somatosensory evoked potentials (pSEPs) in cauda equina and conus medullaris lesions, and evaluation of pSEPs and perineal sympathetic skin response in spinal cord lesions], and support their use in clinical practice. Other tests, particularly those not currently supported by high-level evidence, when employed in individual patients, should be evaluated in the overall clinical context, or otherwise used for research purposes.
Gabriele Buongarzone, Edoardo Monfrini, Giulia Franco, Ilaria Trezzi, Linda Borellini, Emanuele Frattini, Valentina Melzi, Anna Chiara Di Caprio, Dario Ronchi, Giacomo Monzio Compagnoni,et al.
Elsevier BV
Linda Borellini, Filippo Cogiamanian, Giorgio Carrabba, Marco Locatelli, Paolo Rampini, Alessio Di Fonzo, Cristina Bana, Sergio Barbieri, and Gianluca Ardolino
Elsevier BV