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SCOPO DEL LAVORO: La tcMRgFUS consente di effettuare una vera e propria esplorazione neurofunzionale per confermare ed ottimizzare il target lesionale prima di indurre una lesione cerebrale permanente. La scelta del target di trattamento si basa tuttavia su coordinate stereotassiche che non tengono conto delle diversità anatomiche di ciascun individuo. Essendo il paziente vigile durante tutta la durata della procedura, l'ottimizzazione del target di trattamento viene effettuata sulla base del feedback del paziente nel corso della procedura utilizzando sonicazioni di potenza sub-lesionale. Scopo di questo lavoro è valutare retrospettivamente il possibile ruolo della parcellizzazione talamica per l'identificazione del nucleo ventrale intermedio (Vim) in pazienti con tremore essenziale o Parkinson idiopatico unilaterale prevalentemente tremorigeno sottoposti a talamotomia unilaterale mediante tcMRgFUS. MATERIALI E METODI: È’ stato utilizzato uno scanner RM da 1.5T per acquisire sequenze morfologiche (3D FSPGR T1 1x1x1mm) e ultrastrutturali (DTI, b=1000s/mm2, 3x3x3mm, 64 direzioni di gradiente) in pazienti successivamente sottoposti a tcMRgFUS. È stata effettuata una segmentazione delle aree eloquenti cerebrali poi utilizzate come seed per un algoritmo di trattografia probabilistica mirato a rappresentare le proiezioni corticali da e verso il talamo con particolare riferimento alle aree motoria primaria e supplementare, alla corteccia pre-motoria e alla corteccia post-centrale. Le mappe di parcellizzazione talamica così ottenute sono state confrontate con le lesioni indotte mediante tcMRgFUS. RISULTATI: In tutti i casi è stato possibile rappresentare i maggiori gruppi di nuclei talamici che ricevono da o proiettano verso la corteccia cerebrale. È stato possibile identificare un’ottima sovrapposizione tra le mappe di parcellizzazione talamica così ottenute (con particolare riferimento al nucleo VIM) e le lesioni indotte mediante tcMRgFUS. CONCLUSIONI: Questi risultati preliminari lasciano ipotizzare la possibilità di utilizzare questa tecnica durante la pianificazione di trattamenti tcMRgFUS e ottimizzare i tempi di trattamento specie nei casi in cui il target di trattamento si discosti dalle coordinate stereotassiche convenzionali.

Scopo Negli ultimi anni la terapia transcranica ad ultrasuoni focalizzati guidati da risonanza magnetica (tcMRgFUS) per il trattamento di disordini neurologici quali il tremore essenziale (ET) e il Parkinson tremorigeno (PD) è stata effettuata utilizzando esclusivamente scanner RM da 3T. Presentiamo i risultati ottenuti con il primo sistema tcMRgFUS mai integrato con uno scanner RM da 1.5T. Materiali e metodi 50 pazienti (39 ET; 11 PD) sono stati selezionati per essere sottoposti a tcMRgFUS (talamotomia monolaterale; target: nucleo ventrale intermedio, VIM). I pazienti arruolati sono stati valutati prima del trattamento e 2 giorni dopo. L'efficacia del trattamento è stata valutata utilizzando la scala Fahn-Tolosa-Marin (FTM). Una rivalutazione globale è stata eseguita 6, 12 e 24 mesi dopo il trattamento. In tutti i trattamenti è stato utilizzato uno scanner RM a 1.5T per la pianificazione ed il monitoraggio della procedura che è stata effettuata con un sistema tcMRgFUS da 1024 elementi phased-array operante a 650kHz. Risultati Tutti i pazienti con PD meno uno sono stati sottoposti a tcMRgFUS e hanno completato la procedura. Tra i 39 pazienti con ET: 3 hanno interrotto la procedura e 1 non ha subito la procedura dopo il posizionamento del frame stereotassico, tutti i rimanenti hanno completato la procedura con successo. Tutti i pazienti trattati con ET e PD che hanno completato la procedura hanno mostrato un miglioramento immediato della gravità del tremore. Sebbene dopo il trattamento siano stati osservati effetti collaterali da lievi a moderati, nessun evento avverso è durato oltre i 2-3 mesi. Conclusioni La talamotomia del nucleo Vim mediante tcMRgFUS effettuata utilizzando uno scanner RM da 1.5T è risultata essere una un'opzione terapeutica sicura ed efficace per il trattamento del tremore sia nei pazienti con ET e che nei pazienti con PD.

SCOPO DEL LAVORO: Valutare retrospettivamente le caratteristiche di semeiotica neuroradiologica delle lesioni indotte in pazienti sottoposti a talamotomia unilaterale del nucleo Vim mediante l’utilizzo di un sistema trans-cranico ad ultrasuoni focalizzati guidati da RM (tcMRgFUS). MATERIALI E METODI: Cinquanta pazienti sono stati sottoposti a talamotomia mediante tcMRgFUS per tremore essenziale refrattario a terapia medica (n = 39) o per tremore in malattia di Parkinson (n = 11). Esaminando sequenze FRFSE T2-pesate (2mm, no gap) acquisite sia intra-operatoriamente che nel successivo follow-up RM a 48h, è stata valutata la presenza e le dimensioni delle aree lesionali concentriche precedentemente descritte in letteratura (zona I: lesione cavitata; zona II: edema citotossico; zona III: edema vasogenico) e l’eventuale presenza di edema con estensione alla capsula interna omolaterale. Sono stati inoltre valutati i seguenti parametri tecnici: numero di sonicazioni, l'energia erogata e le temperature di trattamento. Le differenze delle caratteristiche neuroradiologiche e delle dimensioni lesionali sono state valutate rispettivamente utilizzando il test McNemar e il paired t-test. RISULTATI: tutte e tre le zone sono state visualizzate intra-operativamente in 26 (52%) pazienti dopo l'ultima sonicazione ad alta energia. Nessuna differenza statisticamente significativa è emersa nel tasso di visualizzazione della zona II (p = 1.000) e della zona III (p = 0.063) sull'imaging intraoperatorio rispetto al follow-up a 48 ore. Il diametro delle zone I e II e lo spessore della zona III sono risultati statisticamente aumentati nel follow-up RM a 48 ore (p

SCOPO DEL LAVORO: La terapia trans-cranica ad ultrasuoni focalizzati guidati da Risonanza Magnetica (tcMRgFUS) è stata recentemente introdotta per il trattamento non invasivo di alcuni disordini del movimento quali il tremore essenziale (ET) ed il Parkinson idiopatico unilaterale prevalentemente tremorigeno (PD). Sebbene con tale tecnica sia possibile generare con successo talamotomie del nucleo Vim nella maggior parte dei pazienti, in alcuni casi si incontrano difficoltà nell’indurre un incremento di temperatura nel target pianificato sufficiente ad indurre e consolidare una lesione permanente. La causa di questi fenomeni è da ricercare nelle caratteristiche specifiche del tavolato cranico cranio che è uno dei maggiori ostacoli alla trasmissione di energia ultrasonora. Scopo del presente lavoro è l’analisi retrospettiva dei fattori legati alle caratteristiche del tavolato cranico ed ai parametri tecnici delle procedure tcMRgFUS cui i pazienti sono stati sottoposti. MATERIALI E METODI: Sono stati analizzati retrospettivamente i dati e i parametri fisici relativi a 52 pazienti sottoposti a talamotomia unilaterale mediante tcMRgFUS (39 con ET e 13 con PD). Sono state analizzate le relazioni tra la temperatura massima raggiunta durante il trattamento, la rapidità di innalzamento di temperatura con l’energia ultrasonora e altri fattori, tra cui superficie del tavolato cranico esposta al fascio HIFU, numero di elementi del trasduttore HIFU utilizzati e il coefficiente di attenuazione del tavolato cranico (Skull Density Ratio, SDR) calcolato a partire da un dataset TC (tecnica sequenziale; 1,25mm di spessore; nessuna inclinazione del gantry). RISULTATI: Tra i vari fattori, la rapidità di innalzamento di temperatura all’aumentare dell’energia ultrasonora rilasciata ha mostrato correlazione positiva con l’SDR (r2=0.765 p

Scopo Indagare i cambiamenti di connettività funzionale nei giocatori patologici (GP) rispetto ai controlli sani (CS) mediante risonanza magnetica funzionale in condizioni di resting state. Materiale e metodi 13 CS e 14 GP sono stati reclutati in questo studio (tutti maschi destrimani, non in terapia farmacologica, età media 35,96 ± 9,56). Tutti i soggetti sono stati sottoposti ad RM encefalo utilizzando uno scanner da 1,5T. I dati di attivazione delle regioni cerebrali tra loro funzionalmente collegate sono stati ottenuti utilizzando un'analisi concat-ICA. Le componenti risultanti sono state quindi confrontate tra i due gruppi. Tra queste mappe sono state prese in considerazione solo quelle che presentavano differenze statisticamente significative (p

BACKGROUND AND OBJECTIVE Optical Coherence Tomography (OCT) enables rapid, non-invasive in vivo measurement of retinal nerve fiber layer (RNFL) thickness, reflecting axonal density within the optic nerve. There is still lack of concordance about the use of OCT in clinical routine as a surrogate measure of brain atrophy. Objective: To investigate the role of OCT as possible predictor of disability, cognitive impairment and neurodegeneration in Multiple Sclerosis (MS). MATERIAL AND METHODS We recruited patients affected by MS according to validated criteria at the Neurological Department of the University of Palermo. Patients performed Stratus OCT- 3 Zeiss to assess RNFL and GCS measurements. Nearly 18 months later, the same patients were re-evaluated. Clinical and cognitive status was assessed also using an extensive neuropsychological battery exploring attention, executive functions and working memory, verbal and visuo-spatial memory, visuospatial functions and language and BICAMS (Brief International Cognitive Assessment for Multiple Sclerosis). Patients performed all subtests of the Italian standardized version. Subjects underwent a single-time-point brain scan using a 1.5T MRI unit; an isotropic 3D-FSPGR T1w sequence was used for brain tissue volume estimation (normalized for subject head size) with tissue-type segmentation by the use of FSL’s package SIENAX. We collected information about disease status, EDSS, relapse rate and current and former therapies. RESULTS Thirty patients (20 women; 27 RR, 2 SP) were recruited for the study. Patients were divided into two groups considering if they were affected by a previous optic neuritis (ON yes) or not (ON no). Ten patients performed the MRI scan. Twenty-two patients were on therapy (5 Interferon beta 1 a, 8 Natalizumab, 8 Fingolimod and 1 azathioprine) and 8 patients don’t take any specific therapy.DISCUSSION AND CONCLUSION.The present study confirms previous data indicating an association between a previous optic neuritis and RFNL thickening. We didn’t observe a significant association with cognitive performances. We observed a significant association also between RFNL thickness and grey matter atrophy independent by neuropsychological performances .There is a need to increase the sample of the study and for longitudinal studies to further clarify the role of OCT as a surrogate marker of degeneration.

PURPOSE: To present our preliminary results achieved with the first Italian installation of a trans-cranial MRI-guided Focused Ultrasound Surgery (tcMRgFUS) certified system for functional neurosurgery. Moreover, to our knowledge, this is the world-first tcMRgFUS system ever installed on a 1.5T MRI unit. Technical issues faced to achieve a safe and effective treatment will be discussed focusing on MR high-resolution live imaging and thermometry sequences optimization. METHOD AND MATERIALS: Patient enrollment was based on indication for functional neurosurgery and evidence of medication-refractory disease; a detailed medical history has been collected together with a complete clinical examination and a neurophysiological assessment. Eligible patients have been screened by MDCT and MRI. TcMRgFUS treatments have been performed by a neurosurgeon with proven experience in functional neurosurgery, and an experienced neuroradiologist, optimizing treatment parameters case by case. RESULTS: Although this is a preliminary experience, the clinical success of our first treatments proves that this promising new technology for non-invasive treatment of various brain disorders can be safety and effectively performed also with the most popular MRI units operating at 1.5T. CONCLUSION: TcMRgFUS treatments are currently performed in a very few centers in the world and only using 3T MRI units. This is the world-first experience of functional neurosurgery successfully performed with a tcMRgFUS installed on the most popular and affordable 1.5T MR units. CLINICAL RELEVANCE/APPLICATION: Direct translational impacts are expected by the use of widely installed 1.5T MRI units both on patient quality of life and on savings in health spending, with reduction in the consumption of drugs, as well as in requests for medical examinations. Being able to use a radiation-free technique like the MRI as a guide and, even further, being able to verify the clinical effectiveness of such an innovative treatment before a permanent lesion is made in the targeted area of the brain is a huge step forward for both interventional radiology and functional neurosurgery.

Introduction: Mild cognitive impairment (MCI) is common in Parkinson’s disease (PD), but the underlying pathological mechanism has not been fully understood. Voxel-based morphometry could be used to evaluate regional atrophy and its relationship with cognitive performances in early PD-MCI. Patients and Methods: One hundred and six patients with PD were recruited from a larger cohort of patients, the Parkinson’s Disease Cognitive Impairment Study (PaCoS). Subject underwent a T1-3D MRI and a complete clinical and neuropsychological evaluation. Patients were divided into PD with normal cognition (PD-NC) and PD-MCI according to the MDS level II criteria–modified for PD-MCI. A subgroup of early patients with short disease duration (≤ 2years) was also identified. VBM analysis between PD-NC and PD-MCI and between early PD-NC and PD-MCI was performed using two-sample t tests with whole-brain statistical threshold of p < 0.001 uncorrected in the entire PD group and p < 0.05 FWE inside ROIs, in the early PD. Results: Forty patients were diagnosed with MCI and 66 were PD-NC. PD-MCI patients showed significant gray matter (GM) reduction in several brain regions, including frontal gyrus, precuneus, angular gyrus, temporal lobe, and cerebellum. Early PD-MCI showed reduction in GM density in superior frontal gyrus and cerebellum. Moreover, correlation analysis between neuropsychological performances and GM volume of early PD-MCI patients showed associations between performances of Raven and superior frontal gyrus volume, Stroop time and inferior frontal gyrus volume, accuracy of Barrage and volume of precuneus. Conclusion: The detection of frontal and cerebellar atrophy, even at an early stage, could be used as an early marker of PD-related cognitive impairment.

Vitamin D is a fat-soluble secosteroid, traditionally considered a key regulator of bone metabolism, calcium and phosphorous homeostasis. Its action is made possible through the binding to the vitamin D receptor (VDR), after which it directly and indirectly modulates the expression of thousands of genes. Vitamin D is important for brain development, mature brain activity and associated with many neurological diseases, including Parkinson’s disease (PD). High frequency of vitamin D deficiency in patients with Parkinson’s disease compared to control population was noted nearly twenty years ago. This finding is of interest given vitamin D’s neuroprotective effect, exerted by the action of neurotrophic factors, regulation of nerve growth or through protection against cytotoxicity. Vitamin D deficiency seems to be related to disease severity and disease progression, evaluated by Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr (H&Y) scale, but not with age of PD onset and duration of disease. Additionally, fall risk has been associated with lower vitamin D levels in PD. However, while the association between vitamin D and motor-symptoms seems to be possible, results of studies investigating the association with non-motor symptoms are conflicting. In addition, very little evidence exists regarding the possibility to use vitamin D supplementation to reduce clinical manifestations and disability in patients with PD. However, considering the positive balance between potential benefits against its limited risks, vitamin D supplementation for PD patients will probably be considered in the near future, if further confirmed in clinical studies.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, characterized by motor and non-motor symptoms due to the degeneration of the pars compacta of the substantia nigra (SNc) with dopaminergic denervation of the striatum. Although the diagnosis of PD is principally based on a clinical assessment, great efforts have been expended over the past two decades to evaluate reliable biomarkers for PD. Among these biomarkers, magnetic resonance imaging (MRI)-based biomarkers may play a key role. Conventional MRI sequences are considered by many in the field to have low sensitivity, while advanced pulse sequences and ultra-high-field MRI techniques have brought many advantages, particularly regarding the study of brainstem and subcortical structures. Nowadays, nigrosome imaging, neuromelanine-sensitive sequences, iron-sensitive sequences, and advanced diffusion weighted imaging techniques afford new insights to the non-invasive study of the SNc. The use of these imaging methods, alone or in combination, may also help to discriminate PD patients from control patients, in addition to discriminating atypical parkinsonian syndromes (PS). A total of 92 articles were identified from an extensive review of the literature on PubMed in order to ascertain the-state-of-the-art of MRI techniques, as applied to the study of SNc in PD patients, as well as their potential future applications as imaging biomarkers of disease. Whilst none of these MRI-imaging biomarkers could be successfully validated for routine clinical practice, in achieving high levels of accuracy and reproducibility in the diagnosis of PD, a multimodal MRI-PD protocol may assist neuroradiologists and clinicians in the early and differential diagnosis of a wide spectrum of neurodegenerative disorders.

The prevalence and impact of imaging findings detected during screening procedures in patients undergoing transcranial MR-guided Focused Ultrasound (tcMRgFUS) thalamotomy for functional neurological disorders has not been assessed yet. This study included 90 patients who fully completed clinical and neuroradiological screenings for tcMRgFUS in a single-center. The presence and location of preoperative imaging findings that could impact the treatment were recorded and classified in three different groups according to their relevance for the eligibility and treatment planning. Furthermore, tcMRgFUS treatments were reviewed to evaluate the number of transducer elements turned off after marking as no pass regions the depicted imaging finding. A total of 146 preoperative imaging findings in 79 (87.8%) patients were detected in the screening population, with a significant correlation with patients’ age (rho = 483, p

Transcranial MR-guided Focused ultrasound (tcMRgFUS) is a surgical procedure that adopts focused ultrasounds beam towards a specific therapeutic target through the intact skull. The convergence of focused ultrasound beams onto the target produces tissue effects through released energy. Regarding neurosurgical applications, tcMRgFUS has been successfully adopted as a non-invasive procedure for ablative purposes such as thalamotomy, pallidotomy, and subthalamotomy for movement disorders. Several studies confirmed the effectiveness of tcMRgFUS in the treatment of several neurological conditions, ranging from motor disorders to psychiatric disorders. Moreover, using low-frequencies tcMRgFUS systems temporarily disrupts the blood–brain barrier, making this procedure suitable in neuro-oncology and neurodegenerative disease for controlled drug delivery. Nowadays, tcMRgFUS represents one of the most promising and fascinating technologies in neuroscience. Since it is an emerging technology, tcMRgFUS is still the subject of countless disparate studies, even if its effectiveness has been already proven in many experimental and therapeutic fields. Therefore, although many studies have been carried out, many others are still needed to increase the degree of knowledge of the innumerable potentials of tcMRgFUS and thus expand the future fields of application of this technology.

Background: High-quality intraoperative imaging is needed for optimal monitoring of patients undergoing transcranial MR-guided Focused Ultrasound (tcMRgFUS) thalamotomy. In this paper, we compare the intraoperative imaging obtained with dedicated FUS-Head coil and standard body radiofrequency coil in tcMRgFUS thalamotomy using 1.5-T MR scanner. Methods: This prospective study included adult patients undergoing tcMRgFUS for treatment of essential tremor. Intraoperative T2-weighted FRFSE sequences were acquired after the last high-energy sonication using a dedicated two-channel FUS-Head (2ch-FUS) coil and body radiofrequency (body-RF) coil. Postoperative follow-ups were performed at 48 h using an eight-channel phased-array (8ch-HEAD) coil. Two readers independently assessed the signal-to-noise ratio (SNR) and evaluated the presence of concentric lesional zones (zone I, II and III). Intraindividual differences in SNR and lesional findings were compared using the Wilcoxon signed rank sum test and McNemar test. Results: Eight patients underwent tcMRgFUS thalamotomy. Intraoperative T2-weighted FRFSE images acquired using the 2ch-FUS coil demonstrated significantly higher SNR (R1 median SNR: 10.54, R2: 9.52) compared to the body-RF coil (R1: 2.96, p &lt, 0.001, R2: 2.99, p &lt, 0.001). The SNR was lower compared to the 48-h follow-up (p &lt, 0.001 for both readers). Intraoperative zone I and zone II were more commonly visualized using the 2ch-FUS coil (R1, p = 0.031 and p = 0.008, R2, p = 0.016, p = 0.008), without significant differences with 48-h follow-up (p &ge, 0.063). The inter-reader agreement was almost perfect for both SNR (ICC: 0.85) and lesional findings (k: 0.82&ndash, 0.91). Conclusions: In the study population, the dedicated 2ch-FUS coil significantly improved the SNR and visualization of lesional zones on intraoperative imaging during tcMRgFUS performed with a 1.5-T MR scanner.

OBJECTIVETranscranial magnetic resonance–guided focused ultrasound surgery (tcMRgFUS) is one of the emerging noninvasive technologies for the treatment of neurological disorders such as essential tremor (ET), idiopathic asymmetrical tremor-dominant Parkinson’s disease (PD), and neuropathic pain. In this clinical series the authors present the preliminary results achieved with the world’s first tcMRgFUS system integrated with a 1.5-T MRI unit.METHODSThe authors describe the results of tcMRgFUS in a sample of patients with ET and with PD who underwent the procedure during the period from January 2015 to September 2017. A monolateral ventralis intermedius nucleus (VIM) thalamic ablation was performed in both ET and PD patients. In all the tcMRgFUS treatments, a 1.5-T MRI scanner was used for both planning and monitoring the procedure.RESULTSDuring the study period, a total of 26 patients underwent tcMRgFUS thalamic ablation for different movement disorders. Among these patients, 18 were diagnosed with ET and 4 were affected by PD. All patients with PD were treated using tcMRgFUS thalamic ablation and all completed the procedure. Among the 18 patients with ET, 13 successfully underwent tcMRgFUS, 4 aborted the procedure during ultrasound delivery, and 1 did not undergo the tcMRgFUS procedure after stereotactic frame placement. Two patients with ET were not included in the results because of the short follow-up duration at the time of this study. A monolateral VIM thalamic ablation in both ET and PD patients was performed. All the enrolled patients were evaluated before the treatment and 2 days after, with a clinical control of the treatment effectiveness using the graphic items of the Fahn-Tolosa-Marin tremor rating scale. A global reevaluation was performed 3 months (17/22 patients) and 6 months (11/22 patients) after the treatment; the reevaluation consisted of clinical questionnaires, neurological tests, and video recordings of the tests. All the ET and PD treated patients who completed the procedure showed an immediate amelioration of tremor severity, with no intra- or posttreatment severe permanent side effects.CONCLUSIONSAlthough this study reports on a small number of patients with a short follow-up duration, the tcMRgFUS procedure using a 1.5-T MRI unit resulted in a safe and effective treatment option for motor symptoms in patients with ET and PD. To the best of the authors’ knowledge, this is the first clinical series in which thalamotomy was performed using tcMRgFUS integrated with a 1.5-T magnet.

In recent years many papers about diagnostic applications of diffusion tensor imaging (DTI) have been published. This is because DTI allows to evaluate in vivo and in a non-invasive way the process of diffusion of water molecules in biological tissues. However, the simplified description of the diffusion process assumed in DTI does not permit to completely map the complex underlying cellular components and structures, which hinder and restrict the diffusion of water molecules. These limitations can be partially overcome by means of diffusion kurtosis imaging (DKI). The aim of this paper is the description of the theory of DKI, a new topic of growing interest in radiology. DKI is a higher order diffusion model that is a straightforward extension of the DTI model. Here, we analyze the physics underlying this method, we report our MRI acquisition protocol with the preprocessing pipeline used and the DKI parametric maps obtained on a 1.5 T scanner, and we review the most relevant clinical applications of this technique in various neurological diseases.

The aim of this study is to describe the frequency of isolated, subtle, neurological abnormalities (ISNAs) in a large population of neurologically and cognitively healthy subjects and to compare ISNAs to various types of MRI-detected cerebrovascular lesions and subcortical brain atrophy in different age classes. 907 subjects were selected from a large, prospective hospital-based study. At baseline neurological examination, 17 ISNAs were selected. Primitive reflexes were the most common ISNAs (35.8%), while dysphagia was the most rarely encountered (0.3%). Measures of small vessel disease, i.e., deep and subcortical white matter hyperintensity and lacunar infarcts as well as subcortical atrophy, were variously associated with ISNAs. In the adult group, the ISNAs were associated with hypertriglyceridemia, TIA, and subcortical lacunar infarcts, while in the elderly-old group they were associated with arterial hypertension, subcortical white matter hyperintensity, and subcortical atrophy. An increased risk of ISNAs was associated with lacunae and white matter hyperintensity in the parietal region. This study shows that white matter hyperintensity, lacunae, and subcortical atrophy are associated with an increased risk of ISNAs in cognitively and neurologically healthy aging subjects. ISNAs are not benign signs. Therefore, adults and elderly people presenting with ISNAs should have access to accurate history and diagnosis to prevent progression of small vessel disease and future neurological and cognitive disabilities.

OBJECTIVE The purpose of this study was to evaluate the usefulness of ultrasound in the preoperative workup of peripheral nerve lesions and illustrate how nerve ultrasonography can be integrated in routine clinical and neurophysiological evaluation and in the management of focal peripheral nerve injuries. The diagnostic role and therapeutic implications of ultrasonography for different neuropathies are described. METHODS The authors analyzed the use of ultrasound in 119 entrapment, tumoral, posttraumatic, or postsurgical nerve injuries of limbs evaluated in 108 patients during 2013 and 2014. All patients were candidates for surgery, and in all cases the evaluation included clinical examination, electrodiagnostic studies (nerve conduction study and electromyography), and ultrasound nerve study. Ultrasound was used to explore the nerve fascicular echotexture, continuity, and surrounding tissues. The maximum cross-sectional area (CSA) and the presence of epineurial hyperechogenicity or intraneural hyper- or hypoechogenicity, of anatomical anomalies, dynamic nerve dislocations, or compressions were recorded. The concordance rate of neurophysiological and ultrasonographic data was analyzed, classifying ultrasound findings as confirming, contributive, or nonconfirming with respect to electrodiagnostic data. The correlation between maximum nerve CSA and neurophysiological severity degree in entrapment syndromes was statistically analyzed. RESULTS Ultrasonography confirmed electrodiagnostic findings in 36.1% of cases and showed a contributive role in the diagnosis and surgical planning in 53.8% of all cases; the findings were negative (“nonconfirming”) in only 10.1% of the patients. In 16% of cases, ultrasound was not only contributive, but had a key diagnostic role in the presence of doubtful electrodiagnostic findings. The contributive role differed according to etiology, being higher for tumors (100%) and for posttraumatic or postsurgical neuropathies (72.2%) than for entrapment neuropathies (43.8%). CONCLUSIONS Ultrasound is a powerful, noninvasive tool for the examination of peripheral nerve injuries, and can guide diagnosis of and surgical strategy for focal peripheral nerve injuries. It allows direct visualization of the cause and extent of nerve lesions and finds its place between electrodiagnostic tests and exploratory surgery. It can provide invaluable information, such as the presence and extent of a mass, scar compression, or neuromas. The authors recommend it as a complement to routine clinical and neurophysiological evaluation and as the first-line imaging modality for masses of suspected nerve origin.

This study is aimed at measuring the variation of functional connectivity between cortical brain regions after tDCS along time. For this purpose we enrolled 20 healthy right-handed subjects.

Introduction: Pseudotumoral-demyelinating lesions are typically characterized by severe difficulties in differential diagnosis from gliomas, metastatic tumors and abscesses. Marburg’s disease (MD) is an extremely rare and aggressive form of Mutiple Sclerosis (MS) with acute onset, rapid neurological deterioration, and poor prognosis. MRI images often show pseudotumoral lesions characterized by mild and focal or, sometimes, ring enhancement. Perhaps, radiological aspect can vary, making necessary hystopathological confirmation. Objectives: There is increasing interest in the role of surgical biopsy for a correct and early diagnosis of pseudotumoral demyelinating lesions. We report an histopathologically confirmed case of MD. Thanks to the analysis of actual literature, our purpose is to ameliorate diagnostic criteria, the timing of treatment and, subsequently, the prognosis of patients affected. Matherials and methods: A 24 years-old woman presented with a sudden onset of motor subaphasia and numbness to the right hemiface, followed, in a few hours by rapid deterioration with mild pyramidal right hemiparesis and complete aphasia. Patient underwent to a CT brain examination which showed three unspecific hypodense lesions: the bigger one, in the left subcortical frontal white matter, and two smaller lesions in the deep parietal and in the right paratrigonal white matter. For better characterization, a brain MRI was performed. The lesions in the right paratrigonal and left parietal white matter where appreciable as highly hyper-intense on TSE-T2 and FLAIR-T2 sequences, hypo-intense on TSE-T1, and responsible for a moderate mass effect on the surrounding structures; the left parietal white matter lesion also showed an incomplete and irregular ring-enhancement. The left subcortical frontal lesion was only mild hyper-intense on TSE-T2 and FLAIR-T2 but strongly hyper-intense on DWI, and a subsequent MRI scan showed a pseudotumoral development with an atypical patchy enhancement. Total body CT scan, auto-antibodies and viral serology on blood and CSF were negative. Isoelectric focusing in agarose gel detected the presence of CSF oligoclonal bands. Steroids were administrated without significant improvement. On the basis of the obtained data, and in consideration of the poor responsiveness to steroids, we performed a neuronavigator-aided biopsy of the main lesion through an open microsurgical approach. Preoperative planning was performed the day before by using contrast agent-enhanced brain CT scan, after positioning markers on the scalp. The exam was then transferred on a data storage device to insert CT images on the neuronavigator. The principal landmarks were used to realize a temporal craniotomy and a small corticectomy centred on the lesion. Finally, we detected, at a depth of about 2 cm, a pathological curdy and whitish tissue, ablated in small fragments and sent for hystological examination. A post-operative CT scan excluded any complications and the patient had a regular course. At demission, neurological exam was slightly better with partial regression of hemiparesis and partial amelioration of speech function. Hystopathological report confirmed the hypothesis of Marburg’s variant of MS. Results and Conclusions: Initial therapeutic approach to MS is pharmacological. However, in some atypical cases, CSF analisys, MRI images and/or clinical course after sterioids administration are not sufficiently diagnostic to completely rule out tumors or abscesses. So, early biopsy is an unavoidable necessity for the differential diagnosis of pseudotumoral-demyelinating lesions, to prevent inappropriate surgical or irradiative treatments and ameliorate the prognosis.

SCOPO DEL LAVORO Presentiamo un caso di una paziente di 24 anni che giunge alla nostra attenzione per la comparsa di disartria come quadro clinico d’esordio di una forma aggressiva di malattia demielinizzante di cui si valuta l’atipica evoluzione neuroradiologica delle lesioni pseudotumorali che la caratterizzano e le possibili diagnosi differenziali. MATERIALI E METODI La paziente dopo una prima valutazione in PS è stata sottoposta a TC encefalo, ricoverata presso l’U.O. di Neurologia, sottoposta a controlli RM seriati (anche con tecniche avanzate); durante la degenza è stata inoltre effettuata una biopsia stereotassica. RISULTATI La TC ha rilevato almeno tre lesioni ipodense: a sinistra, nella sostanza bianca sottocorticale frontale e nella sostanza bianca parietale profonda, a destra, in sede paratrigonale. Le ultime due, ad un approfondimento diagnostico con esame RM, mostravano un aspetto leggermente rigonfio, segnale elevato nelle sequenze a lungo TR ed un cercine di enhancement incompleto dopo contrasto. L’area lesionale frontale, invece, notevolmente più estesa delle altre, mostrava un segnale più disomogeneo nelle pesature a lungo TR (come costituita da più lesioni focali tendenti alla confluenza), restrizione della diffusione in ADC in assenza di enhancement dopo contrasto. Quest’ultima lesione, ai successivi controlli si è infine appalesata, intorno al primo mese dall’esordio clinico, come una grossa lesione pseudotumorale con enhancement tuttavia atipico per malattia demielinizzante. CONCLUSIONI La clinica di presentazione, la rachicentesi e la semeiotica RM delle lesioni di dimensioni minori erano compatibili con un quadro di malattia demielinizzante; tuttavia, non è stato possibile escludere che la grossa lesione in sede frontale sinistra potesse avere altra natura. L’ipotesi diagnostica di una forma di malattia demielinizzante nel nostro caso fu confermata dalla biopsia stereotassica, eseguita in considerazione della mancata risposta alla terapia medica steroidea e della peculiare severità del quadro clinico inesorabilmente ingravescente. All’esame istologico, nei frammenti di tessuto cerebrale bioptizzato, sono state individuate aree di demielinizzazione, negative per la proteina basica della mielina (MBP), isolati linfociti T (CD3+) ed astrocitosi reattiva. Le lesioni demielinizzanti pseudotumorali pongono non pochi problemi di diagnosi differenziale. Il nostro caso, appare eccezionale in letteratura per la singolare evoluzione della lesione di maggior dimensioni, che da un aspetto iniziale di lesione “stroke-like”, in un periodo non superiore ad un mese, si appalesa nei successivi controlli come una lesione pseudotumorale con enhancement atipico, verosimile espressione di una atipica presentazione di una variante di sclerosi multipla (Marburg?).

PURPOSE: to show the relevance of peripheral nerve ultrasound imaging as a supplementary technique in a clinical neurophysiological evaluation. METHODS: peripheral nerves ultrasound (US) examination was performed in patients with a medical history of nerve entrapment and/or post-traumatic neuropathy but with clinical or neurophysiological unusual findings. A 10-18 MHz transducer was used. RESULTS: we recruited 50 patients with clinical evidence of peripheral neuropathies (25M, 25F): 24 median nerves, 1 anterior interosseous, 14 ulnar, 3 brachial plexus, 2 posterior interosseus, 1 superficial radial, 1 superficial peroneal and 4 common peroneal nerves. Overall 20/50 patients had a history of trauma: 4/24 patients with median pathology, 6/14 ulnar, 3/4 common peroneal, 1/2 posterior interosseous and all cases of involvement of the brachial plexus, superficial peroneal and superficial radial nerves. CONCLUSIONS: our data show that peripheral nerve US is advisable: in all patients with post-traumatic etiology (40%) as it could reveal neuromas and neurotmesis; in all post-surgical iatrogenic onset neuropathies for the uncommon sites of injury; in severe diseases with not evocable nerve at the neurophysiological examination; in patients with diffuse pre-existing (and confounding) neurophysiological alterations (but with clinical suspect of new neuropathy); in entrapment neuropathies for screening purpose (we found concomitant tenosynovitis in 21.7% of carpal tunnel syndromes; dynamic ulnar nerve luxation at the elbow in 28.5% of case); in all brachial plexus pathologies as multiple sites of injury – i.e. radial, ulnar and posterior interosseous have been documented; for early selection of surgical candidates and post-surgical patients monitoring.

Introduzione: le patologie dei nervi sono causa di disabilità nella popolazione giovane adulta affetta e motivo di contenzioso medico-legale per molti chirurghi. Obiettivi: valutare la rilevanza dell’ecografia del nervo e dell’esame neurofisiologico nella valutazione prechirurgica e nel follow-up post-chirurgico ai fini diagnostici, prognostici e di adeguata programmazione terapeutica. Materiali e Metodi: pazienti con patologia da intrappolamento o post-traumatica sono stati sottoposti a valutazione clinica, neurofisiologica ed ecografica. Risultati: abbiamo studiato 50 neuropatie (25M, 25F): 23 nervi mediani, 1 interosseo anteriore, 14 nervi ulnari, 3 plessi brachiale, 2 interossei posteriori, 1 radiale superficiale, 1 peroneo superficiale and 4 peronei comuni. Complessivamente 20/50 pazienti avevano una storia di trauma: 4/23 pazienti con patologia del n. mediano, 6/14 ulnari, 3/4 peronei comuni 1/2 interossei posteriori e tutti i casi di coinvolgimento di plesso brachiale, peroneo superficiale e radiale superficiale reclutati. Conclusioni L’esame neurofisiologico, guidato dall’esame clinico, rappresenta tuttora il gold-standard diagnostico e permette di documentare sede della lesione, entità e fibre coinvolte (motorie/sensitive); l’esame ecografico permette di documentare l’etiologia, la presenza di discontinuità dei nervi (neuromi) e di fibrosi epineurale ed intraneurale. L’esame ecografico, effettuato ad integrazione della valutazione clinica e neurofisiologica, è consigliabile in tutti i casi di neuropatia post-traumatica (o con inelicitabilità del nervo), nei pazienti acuti o anche a distanza di mesi dal trauma; è indicato nei pazienti con alterazioni neurofisiologiche dubbie o diffuse ed in tutte le patologie di plesso brachiale per la frequente presenza di multiple sedi di lesione prossimali e distali associate al trauma. L’approccio integrato neurofisiologico ed ecografico fornisce indicazioni funzionali ed anatomiche preziose per il chirurgo, ed è utilizzabile per programmare l’intervento o una revisione chirurgica e documentare il miglioramento post-chirurgico.

Sudden sensorineural hearing loss is a clinical condition characterized by a sudden onset of unilateral or bilateral hearing loss. In recent years sudden deafness has been frequently described in association with anterior inferior cerebellar artery (AICA) infarction generally presenting along with other brainstem and cerebellar signs such as ataxia, dysmetria and peripheral facial palsy. The authors report a rare clinical case of a 53-year-old man who suddenly developed hearing loss and tinnitus without any brainstem or cerebellar signs. Computed tomography of his brain was normal, and the audiological results localized the lesion causing deafness to the inner ear. Surprisingly, magnetic resonance imaging showed an ischemic infarct in the right AICA territory. This case represents the fifth in the literature to date but it confirms that AICA occlusion can cause sudden deafness even without brainstem or cerebellar signs. Therefore, we recommend submitting the patient for neuroimaging, as an emergency, in order to exclude infarction of the AICA territory. By doing this, it may be possible to limit the extent of the lesion by commencing early therapy.

Gli autori riportano un raro caso clinico di una paziente di 77 anni che giunge alla nostra osservazione in regime di urgenza per vertigine improvvisa associata a nausea e vomito, stato confusionale, atassia, paralisi completa del VI nervo cranico di destra con strabismo convergente, segni di sofferenza del IX, X ed XI nervo cranico omolaterali all’abducente e iniziale comparsa di segni statici e dinamici di paralisi periferica del VII nervo cranico di destra. L’insorgenza improvvisa di Sindromi paralitiche associate, anteriori e posteriori, ha indirizzato verso il sospetto di lesione occupante spazio a sede in fossa cranica posteriore/tronco encefalo richiedendo pertanto l’ausilio della diagnostica per immagini. Lo studio TC encefalo ha evidenziato la presenza di una formazione espansiva a densità similliquorale in fossa cranica posteriore, angolo ponto-cerebellare destro, nel cui contesto si è evidenziata area iperdensa da riferire a sanguinamento recente, con livello fluido-fluido, responsabile di importante effetto massa sulle strutture parenchimali contigue ed in particolare sulla sezione destra del tronco encefalo e dell’emisfero cerebellare omolaterale, con severa impronta sul IV ventricolo. L’assenza, alla valutazione della finestra per osso, di segni indiretti tipici da neurinoma stato acustico con interessamento del condotto uditivo interno (svasamento del porus e/o ampliamento del canale acustico interno) è risultata compatibile con la riferita negatività di pregressi segni clinici di pertinenza audio vestibolare. Lo studio RM encefalo eseguito tra le altre in tecnica 3D-FIESTA e 3D T1 FAT-SAT dopo MdC ev. ha permesso di identificare con certezza una lesione espansiva extra-assiale con componente tissutale solida che origina nel condotto uditivo interno da riferire a neurinoma. Nel contesto della componente extracanalare dello stesso, si riconosce un'unica ampia cavità cistica nel cui contesto si apprezza livello fluido-fluido per la presenza in sede declive di cataboliti dell’emoglobina come da sanguinamento recente intralesionale, verosimilmente responsabile del rapido aumento volumetrico della lesione stessa che giustificherebbe l’esordio clinico acuto con “Sindrome paralitica associata anteriore e posteriore”.

Marburg's disease (MD) is an extremely rare and aggressive form of multiple sclerosis (MS). In some cases, MD presents with tumefactive demyelinating lesions with a “tumor-like” appearance in MRI images, for which it may be difficult to achieve a form of differential diagnosis between definitive tumors or abscesses. Here we report a case of MD histopathologically confirmed after neuronavigationguided biopsy. Postoperative course was uneventful and following discharge, the patient attended outpatient follow-up appointments and received i.v. cyclophopsphamide, achieving progressive clinical remission. A nine-month follow-up brain MRI scan with gadolinium showed no signs of progressing demyelinating disease with an evident reduction of the biopsied lesion, and almost complete retrogression of the other two lesions. In our opinion, and through the analysis of currently available literature, early neuronavigation-guided biopsy is a highly recommend, valuable, and safe diagnostic tool; it is also preferable to stereotactic biopsy, since its benefits include a very low bleeding rate and brain damage risk, with minimum mortality and morbidity rates. It also allows the identification of the specific histological pattern, helping to select the best medical treatment approach and contributing to increase patient outcome and life expectancy.

n this report, we describe the case of a patient who has remained in a comatose state for more than one year after a traumatic and hypoxic brain injury. This state, which we refer to as long-lasting coma (LLC), may be a disorder of consciousness with significantly different features from those of conventional coma, the vegeta- tive state, or brain death. On the basis of clinical, neu- rophysiological and neuroimaging data, we hypothe- size that a multilevel involvement of the ascending reticular activating system is required in LLC. This description may be useful for the identification of other patients suffering from this severe disorder of con- sciousness, which raises important ethical issues.