Do patients' and referral centers' characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register.

BACKGROUND: Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. METHODS: This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000-2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing-remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers' characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. RESULTS: In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. DISCUSSION: Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers' characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.

Multiple sclerosis and non-dystrophic myotonias: do they share a common pathophysiology?

Some patients with multiple sclerosis (MS) complain of symptoms, such as myokymia, myotonia, spasms, and stiffness, which have been demonstrated to be due to a concurrent non-dystrophic myotonia, i.e. myotonia congenita or paramyotonia congenita. Beyond the known casual association between MS and non-dystrophic myotonia, a channelopathy representing a primary trait of MS rather than an epiphenomenon of demyelization (i.e., an acquired channelopathy) may exist. Indeed, the finding of MS patients with no genetic evidence of non-dystrophic myotonia but showing a clinical picture resembling this condition would support this hypothesis. Thirty patients with MS and no concurrent diagnosis of myotonia congenita or paramyotonia congenita were submitted to the Fournier protocol. Some of these MS patients presented abnormal muscle excitability with scarce myotonic discharges, but only a few of them had clinical features compatible with myotonia congenita or paramyotonia congenita syndromes. Even though the low number of recruited patients did not allow a robust statistical analysis, our data seemed to indicate the presence of an ion channel dysfunction that is independent of the acquired channelopathies and likely represents a common pathophysiological mechanism underlying a unique channelopathy simultaneously involving the peripheral and the central nervous system in individuals with MS. Confirming the presence of such a primary channelopathy in MS patients is of non-negligible importance, since dysfunction of ion channels may represent a suitable therapeutic target in MS.

Neural correlates of fatigue in multiple sclerosis: a combined neurophysiological and neuroimaging approach (R1).

The present study is aimed at further exploring structural and functional correlates of fatigue in Relapsing- Remitting Multiple Sclerosis (RRMS) patients by using a combined approach by means of transcranial magnetic stimulation (TMS) and a Diffusion Tensor Imaging (DTI). The physiopathology of fatigue in MS is still poorly understood, although a variety of pathogenic mechanisms has been proposed. Our working hypothesis is that diffuse microstructural white matter damage may subtend the cortico-subcortical functional disconnection described in patients with MS and fatigue. We enrolled 30 RRMS patients (mean age 39±13; age range 24-63 years) with mild neurological impairment Expanded Disability Status Scale <3.5, divided into two groups on the basis of their fatigue severity scale (FSS) scoring (cutoff ≥ 4). All the patients underwent a neurological evaluation, a brain MRI acquisition (including DTI study) and a neurophysiological assessment by means of TMS in a pre-movement facilitation paradigm. Our data showed a significant mean diffusivity (MD) increase (p=0.036) in left thalamo-frontal reconstructions in the MS patients with fatigue compared to those classified as non-fatigued. Moreover, significant correlations were observed between FSS scale and MD as well as planar coefficient (CP) values extracted from frontal-thalamic connections bilaterally. Instead, the pre-movement facilitation showed a significant difference between the groups with particular regard to the Reaction Time- MEP50ms amplitude (p=0.03). Our work confirms that fatigue is associated with a disruption of brain networks involved in motor preparation processes, depending on several frontal-thalamic pathways. Such findings can have an important role when dealing with fatigue management in MS patients and could be eventually used as prognostic marker of MS course.

Analysis of Italian regulations on pathways of care for patients in a vegetative or minimally conscious state.

Different rehabilitation models for persons diagnosed with disorders of consciousness have been proposed in Europe during the last decade. In Italy, the Ministry of Health has defined a national healthcare model, although, to date, there is a lack of information on how this has been implemented at regional level. The INCARICO project collected information on different regional regulations, analysing ethical aspects and mapping care facilities (numbers of beds and medical units) in eleven regional territories. The researchers found a total of 106 laws; differences emerged both between regions and versus the national model, showing that patients with the same diagnosis may follow different pathways of care. An ongoing cultural shift from a treatment-oriented medical approach towards a care-oriented integrated biopsychosocial approach was found in all the welfare and healthcare systems analysed. Future studies are needed to explore the relationship between healthcare systems and the quality of services provided.

Mesenchymal stem cell therapy in Parkinson's disease animal models.

Parkinson's disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, and as a consequence, by decreased dopamine levels in the striatum. Currently available therapies are not able to stop or reverse the progression of the disease. A novel therapeutic approach is based on cell therapy with stem cells, in order to replace degenerated neurons. Among stem cells, mesenchymal stem cells seemed the most promising thanks to their capacities to differentiate toward dopaminergic neurons and to release neurotrophic factors. Indeed, mesenchymal stem cells are able to produce different molecules with immunomodulatory, neuroprotective, angiogenic, chemotactic effects and that stimulate differentiation of resident stem cells. Mesenchymal stem cells were isolated for the first time from bone marrow, but can be collected also from adipose tissue, umbilical cord and other tissues. In this review, we focused our attention on mesenchymal stem cells derived from different sources and their application in Parkinson's disease animal models.

Should we care about sativex-induced neurobehavioral effects? A 6-month follow-up study.

OBJECTIVE: Sativex® is an exclusive cannabinoid-based drug approved for the treatment of spasticity due to Multiple Sclerosis (MS). The most common side effects include dizziness, nausea, and somnolence. However, it is still under debate whether the drug could cause negative cognitive effects. The aim of our study was to investigate the effect of Sativex® on functional and psychological status in cannabis-naïve MS patients. PATIENTS AND METHODS: All the study participants (i.e. 40 patients affected by MS) underwent a specific clinical and neuropsychological assessment to investigate spasticity and associated symptoms, besides the cognitive and psychiatric domains commonly impaired in MS, before and after 1 and 6 months of Sativex® administration. RESULTS: After the treatment, we did not observe any significant neurobehavioral impairment in all the patients, but one. CONCLUSIONS: Our findings suggest that Sativex® treatment does not significantly affect the cognitive and neurobehavioral functions. However, the study supports the relevance of an extensive neuropsychological evaluation in MS patients selected for the drug administration, in an attempt to early detect the uncommon but important neurobehavioral side effects.

Cortical connectivity and memory performance in cognitive decline: A study via graph theory from EEG data.

Functional brain abnormalities including memory loss are found to be associated with pathological changes in connectivity and network neural structures. Alzheimer's disease (AD) interferes with memory formation from the molecular level, to synaptic functions and neural networks organization. Here, we determined whether brain connectivity of resting-state networks correlate with memory in patients affected by AD and in subjects with mild cognitive impairment (MCI). One hundred and forty-four subjects were recruited: 70 AD (MMSE Mini Mental State Evaluation 21.4), 50 MCI (MMSE 25.2) and 24 healthy subjects (MMSE 29.8). Undirected and weighted cortical brain network was built to evaluate graph core measures to obtain Small World parameters. eLORETA lagged linear connectivity as extracted by electroencephalogram (EEG) signals was used to weight the network. A high statistical correlation between Small World and memory performance was found. Namely, higher Small World characteristic in EEG gamma frequency band during the resting state, better performance in short-term memory as evaluated by the digit span tests. Such Small World pattern might represent a biomarker of working memory impairment in older people both in physiological and pathological conditions.

Do unresponsive wakefulness syndrome patients feel pain? Role of laser-evoked potential-induced gamma-band oscillations in detecting cortical pain processing.

It has been proposed that a neural signature of aware pain perception could be represented by the modulation of gamma-band oscillation (GBO) power induced by nociceptive repetitive laser stimulation (RLS). The aim of our study was to correlate the RLS-induced GBO modulation with the Nociception Coma Scale-Revised (NCS-R) scores (a validated scale assessing possible aware pain perception in patients with chronic disorders of consciousness), in an attempt to differentiate unresponsive wakefulness syndrome (UWS) patients from minimally conscious state (MCS) ones (both of them are awake but exhibit no or limited and fluctuant behavioral signs of awareness and mentation, and low and high NCS-R scores, respectively). In addition, we attempted to identify those among UWS patients who probably experienced pain at covert level (i.e. being aware but unable to show pain-related purposeful behaviors, which are those sustained, reproducible, and voluntary behavioral responses to nociceptive stimuli). Notably, the possibility of clearly differentiating UWS from MCS patients has outmost consequences concerning prognosis (worse in UWS) and adequate pain treatment. RLS consisted in 80 trains of three laser stimuli (delivered at 1Hz), at four different energies, able to evoke Aδ-fiber related laser evoked potentials. After each train, we assessed the NCS-R score. EEG was divided into epochs according to the laser trains, and the obtained epochs were classified in four categories according to the NCS-R score magnitude. We quantified the GBO absolute power for each category. RLS protocol induced a strongly correlated increase in GBO power and NCS-R score (the higher the laser stimulation intensity, the higher the NCS-R, independently of stimulus repetition) in all the MCS patients, thus confirming the presence of aware pain processing. Nonetheless, such findings were present even in five UWS individuals. This could suggest the presence of covert pain processing in such subjects, despite the low NCS-R scores. In conclusion, RSL-induced GBO power evaluation could be helpful in the differential diagnosis between MCS and UWS patients, besides the clinical assessment, and in identifying covert pain perception in some UWS individuals.

Is ß-catenin neutralization cross-involved in the mechanisms mediated by natalizumab action?

Aberrant activation of Wnt/ß-catenin signaling pathway is commonly associated to cancer development. However, molecular mechanisms controlling Wnt/ß-catenin signaling pathway have been clarified only in part. Here, we show that ß-catenin is differently modulated in patients with multiple sclerosis (MS), displaying that different pharmacological treatments used for clinical MS management cause different nuclear expression levels of ß-catenin. Proteins extracted by peripheral blood mononuclear cells were assessed to evaluate the western blot expression levels of ß-catenin. Analyzing our results, we realized that ß-catenin is totally inhibited by Natalizumab and could have a role in MS management. This could offer new promising studies focused on the possible therapeutic control of ß-catenin translocation.

Assessment of nociceptive system in vegetative and minimally conscious state by using laser evoked potentials.

PRIMARY OBJECTIVE: The aim of this study is to assess if laser evoked potentials (LEPs) examination should be considered as an objective evidence of potential or residual pain perception capacity in vegetative (VS) and minimally conscious state (MCS) patients and if it could be a feasible methodology in order to differentiate these two clinical entities. RESEARCH DESIGN: This is a cross-sectional observational study focusing on the role of LEP examination, which is an easy and objective neurophysiological approach of the nociceptive system. METHODS AND PROCEDURES: Thirteen VS and 10 MCS patients were enrolled. All subjects were evaluated clinically by using validated behavioural scales and underwent to upper and lower limbs LEP recording. MAIN OUTCOMES AND RESULTS: Intra-group LEPs analysis in VS patients highlighted significant differences for N2P2 latency (p = 0.036) and amplitude (p = 0.018). Inter-group LEPs analysis showed significant differences in post-anoxic condition for N2P2 latency (p = 0.034), amplitude (p = 0.034) and a trend in N2P2 latency in brain trauma (p = 0.07). Interestingly, correlation analysis showed a significant relationship between N2P2 amplitude and Coma Recovery Scale-Revised scoring in the post-traumatic VS (r = 0.823, p = 0.044). CONCLUSIONS: The findings lead to detection of potential markers of conscious pain perception in patients with DOC, with important impact on therapeutic and rehabilitative management, and provide new information that may allow a better differential diagnosis.

Small-worldness characteristics and its gender relation in specific hemispheric networks.

Aim of this study was to verify whether the topological organization of human brain functional networks is different for males and females in resting state EEGs. Undirected and weighted brain networks were computed by eLORETA lagged linear connectivity in 130 subjects (59 males and 71 females) within each hemisphere and in four resting state networks (Attentional Network (AN), Frontal Network (FN), Sensorimotor Network (SN), Default Mode Network (DMN)). We found that small-world (SW) architecture in the left hemisphere Frontal network presented differences in both delta and alpha band, in particular lower values in delta and higher in alpha 2 in males respect to females while in the right hemisphere differences were found in lower values of SW in males respect to females in gamma Attentional, delta Sensorimotor and delta and gamma DMNs. Gender small-worldness differences in some of resting state networks indicated that there are specific brain differences in the EEG rhythms when the brain is in the resting-state condition. These specific regions could be considered related to the functions of behavior and cognition and should be taken into account both for research on healthy and brain diseased subjects.

4(α-L-RHAMNOSYLOXY)-BENZYL ISOTHIOCYANATE, A BIOACTIVE PHYTOCHEMICAL THAT DEFENDS CEREBRAL TISSUE AND PREVENTS SEVERE DAMAGE INDUCED BY FOCAL ISCHEMIA/REPERFUSION.

Natural compounds are a promising source to treat several pathologies. The present study shows the in vivo pharmacological beneficial effect of 4(α-L-rhamnosyloxy)-benzyl isothiocyanate (glucomoringin isothiocyanate; GMG-ITC) obtained from glucomoringin (GMG; 4(α;-L-rhamnosyloxy)- benzyl glucosinolate), purified from Moringa oleifera seeds and hydrolyzed by myrosinase enzyme (β-thioglucoside glucohydrolase; E.C. 3.2.1.147). Cerebral ischemia/reperfusion (CIR) was induced in rats according to a classic model of carotid artery occlusion for a time period of 1 h and the reperfusion time was prolonged for seven days. GMG-ITC (3.5 mg GMG/ml plus 30 µl enzyme/rat; one ml i.p./rat) was administered 15 min after the beginning of ischemia and daily. The results clearly show that GMG-ITC possesses the capability to counteract the CIR-induced damage reducing TNF-alpha release, IκB-alpha cytosolic degradation/NFκBp65 nuclear translocation, as well as several other direct or indirect markers of inflammation (phospho-ERK p42/44, p-selectin) and oxidative stress (inducible Nitric Oxide Synthase (iNOS), MMP-9). GMG-ITC was shown to exert neuroprotective properties in preventing CIR-induced damage and the related cascade of inflammatory and oxidative mediators that exacerbate the progression of this disease in an experimental rat model. Our results clearly show that the tested phytochemical GMG-ITC possesses the capability to counteract CIR-induced damage.

GLYOXALASE I A111E, PARAOXONASE 1 Q192R AND L55M POLYMORPHISMS IN ITALIAN PATIENTS WITH SPORADIC CEREBRAL CAVERNOUS MALFORMATIONS: A PILOT STUDY.

It is already known that the conditions of increased oxidative stress are associated to a greater susceptibility to vascular malformations including cerebral cavernous malformations (CCMs). These are vascular lesions of the CNS characterized by abnormally enlarged capillary cavities that can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes: CCM1(Krit1), CCM2 (MGC4607) and CCM3 (PDCD10). Polymorphisms in the genes encoding for enzymes involved in the antioxidant systems such as glyoxalase I (GLO I) and paraoxonase I (PON I) could influence individual susceptibility to the vascular malformations. A single nucleotide polymorphism was identified in the exon 4 of GLO 1 gene that causes an amino acid substitution of Ala for Glu (Ala111Glu). Two common polymorphisms have been described in the coding region of PON1, which lead to glutamine → arginine substitution at 192 (Q192R) and a leucine → methionine substitution at 55 (L55M). The polymorphisms were characterized in 59 patients without mutations in the CCM genes versus 213 healthy controls by PCR/RFLP methods using DNA from lymphocytes. We found that the frequency of patients carrying the GLO1 A/E genotype among the case group (56%) was four-fold higher than among the controls (14.1%). In the cohort of CCM patients, an increase in the frequency of PON192 Q/R genotype was observed (39% in the CCM group versus 3.7% in the healthy controls). Similarly, an increase was observed in the proportion of individuals with the genotype R/R in the disease group (5%) in respect to the normal healthy cohort (0.5%). Finally, the frequency of the PON55 heterozygotes L/M genotype was 29% in patients with CCMs and 4% in the healthy controls. The same trend was observed in PON55 homozygous M/M genotype frequency (CCMs 20% vs controls 10%). The present study aimed to investigate the possible association of GLO1 A111E, PON1 Q192R and L55M polymorphisms with the risk of CCMs. We found that individuals with the GLO1 A /E genotype, PON192/QR-RR genotypes and PON55/LM-MM genotypes had a significantly higher risk of CCMs compared with the other genotypes. However, because CCM is a heterogeneous disease, other additional factors might be involved in the initiation and progression of CCM disease.

Clinical evaluation of the oral health status in vascular-type dementia patients. A case-control study.

AIM: The aim of this study was to evaluate the oral health status in patients with vascular dementia (VaD). Moreover, the association of the disease severity and the patients' cognitive and functional impairment with the oral findings have been recorded. METHODS: The study was directed on the study group (86 VaD patients) and the control group (82 healthy volunteers of the same age) from the IRCSS Neurolesi Bonino-Pulejo in Messina, Italy. Cognitive status was evaluated with the MMSE scoring system. Oral parameters, such as decaying, missing, filled teeth (DMFT) index, plaque index (PI), periodontal probing depth (PPD) and bleeding on probing (BOP) were evaluated in all patients. Denture condition and denture-induced stomatitis were also analysed. The frequency of untreated caries, periodontal diseases and missing teeth of the Study Group was significantly higher than in Control Group. RESULTS: Particularly, VaD patients presented higher number of decayed teeth and deeper periodontal pockets. Decreased cognitive functions in VaD patients have been demonstrated to result in a decline of denture care and increased denture-related mucosal lesions. CONCLUSION: These results underlined that clinicians should direct high attention to oral hygiene of patients with VaD in order to prevent the evolution of those pathologic dental and periodontal conditions, especially in patients with decreased cognitive functions.

Purified Cannabidiol, the main non-psychotropic component of Cannabis sativa, alone, counteracts neuronal apoptosis in experimental multiple sclerosis.

OBJECTIVE: Multiple Sclerosis (MS) is a global concern disease leading to a progressive, chronic and demyelinating condition, affecting the central nervous system (CNS). The pathology has an inflammatory/autoimmune origin; nevertheless, neuronal cell death mechanisms are not to be underestimated. The present study was designed to test the effects of intraperitoneal administration of cannabidiol (CBD), the main non-psychotropic cannabinoid of Cannabis sativa (CS), in an experimental model of MS. The aim is to evaluate the capability of CBD administration to thwart the cascade of mediators involved in MS-induced apoptosis. MATERIALS AND METHODS: Experimental Autoimmune Encephalomyelitis (EAE) was induced by immunization with myelin oligodendroglial glycoprotein (MOG)35-55 peptide in mice. After immunization, mice were observed daily for signs of EAE and weight loss. Disease signs were evaluated using a standardized scoring system. RESULTS: Immunohistochemical and Western blot assessments of key apoptotic markers reveal that CBD treatment is able to avoid Fas pathway activation, phospho-ERK p42/44 and cleaved caspase-3 triggering as well as alterations in mitochondrial permeability due to Bax/Bcl-2 unbalance. Moreover, CBD interferes with p53-p21 axis activation. As results, the absence of tissue apobody formation in spinal cord tissues of EAE-mice treated with CBD was established. Most of therapeutic properties of CS are currently ascribed to the psychotropic effects of phenylterpenoid delta-9 tetrahydrocannabinol. CONCLUSIONS: We have demonstrated that, alone, purified CBD possesses an anti-apoptotic power against the neurodegenerative processes underlying MS development. This represents an interesting new profile of CBD that could lead to its introduction in the clinical management of MS.

Botulinum toxin type A potentiates the effect of neuromotor rehabilitation of Pisa syndrome in Parkinson disease: a placebo controlled study.

INTRODUCTION: Pisa syndrome (PS) is a tonic lateral flexion of trunk that represents a disabling complication of advanced Parkinson disease (PD). Conventional rehabilitation treatment (CT) ameliorates axial posture and trunk mobility in PD patients, but the improvement tends to wane in 4-6 months. Botulin toxin (BT) may reduce muscle hyperactivity, therefore improving CT effectiveness. We evaluated whether the injection of incabotulinum toxin type A (iBTA) into the hyperactive trunk muscles might improve the effectiveness of rehabilitation in a group of PD patients with PS. METHODS: Twenty-six PD patients were enrolled in a randomized placebo-controlled trial. Group A was treated with iBTA before undergoing CT (a 4-week intensive programme), while Group B received saline before the 4-week CT treatment. Patients were evaluated at baseline, at the end of the rehabilitative period, 3 and 6 months with kinematic analysis of movement, UPDRS, Functional Independence Measure and Visual Analog Scale for pain. RESULTS: At the end of the rehabilitation period, both groups improved significantly in terms of static postural alignment and of range of motion. Group A showed a significantly more marked reduction in pain score as compared with Group B and a more prolonged efficacy on several clinical and kinematic variables. CONCLUSIONS: Our preliminary data suggest that BT may be considered an important addition to the rehabilitation programme for PD subjects with PS for improving axial posture and trunk mobility, as well as for a better control of pain.

The protective effects of bioactive (RS)-glucoraphanin on the permeability of the mice blood-brain barrier following experimental autoimmune encephalomyelitis.

OBJECTIVES: Alterations in blood-brain barrier (BBB) permeability are due to the disruption of the Tight Junctions (TJs), large multiprotein complexes important for the maintenance of structural integrity and for permeability of the barrier. In this experimental study we evaluated the neuroprotective role of (RS)-glucoraphanin, a glucosinolate present in Brassicaceae, notably in Tuscan black kale, and bioactivated with myrosinase enzyme (bioactive RS-GRA) (10 mg/kg/d intraperitoneally), to prevent the dysfunction of BBB, in an experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). MATERIALS AND METHODS: EAE was induced by immunization with myelin oligodendroglial glycoprotein peptide (MOG)35-55 in mice. By western blot analysis of brain tissues, we evaluated expression and distribution of the TJ-associated proteins, claudin-1, -3, -5 and ZO-1. Additionally, in order to gain a better insight into the mechanisms of action of bioactive RS-GRA, we investigated Foxp3, ERK1/2 and caspase 3 expression associated both to inflammatory response as well as to apoptotic pathway. RESULTS: Our results demonstrated that treatment with bioactive RS-GRA counteracts the alteration of all these parameters and preserves TJ integrity through an antinflammatory and antiapoptotic activity during MS. CONCLUSIONS: Bioactive RS-GRA, could be a therapeutic perspective helpful in preventing dysfunction of the BBB.

Cortical reorganization in multiple sclerosis after intrathecal baclofen therapy.

Our objective was to assess the role of Intrathecal Baclofen Therapy (ITB) in the cortical reorganization in a patient affected by multiple sclerosis (MS) undergoing physical therapy. We reported a case of a woman affected by MS and severe spasticity, who performed an fMRI examination, before and after the ITB implantation. The subject showed controlateral motor cortex activation after motor task. After a month of ITB implantation, patient showed ipsilateral and controlateral motor cortex activation although with a broader extension. fMRI examination supported the hypothesis of a central influence in patients who undergo physiotherapy and therapy with ITB.

Differences between conventional and nonconventional MRI techniques in Parkinson's disease.

Magnetic resonance imaging (MRI) provides an in vivo assessment of cortical and subcortical regions affected in Parkinson's disease (PD). This review summarizes the most important conventional and non-conventional MRI techniques applied in this field. Standard neuroimaging techniques have played a marginal role in the diagnosis and follow-up of PD, essentially being used only to discriminate atypical syndromes from PD, to exclude secondary causes such as vascular lesions, and to confirm the absence of specific imaging features found in atypical parkinsonisms. However, non-conventional MRI techniques, i.e. new neuroimaging approaches such as magnetic resonance spectroscopy, diffusion tensor imaging, and functional MRI, may allow the detection of structural, functional and metabolic changes useful not only for differential diagnosis, but also for early diagnosis and outcome and treatment monitoring in PD. In addition, we illustrate the advantages of high-field MRI over lower magnetic fields, highlighting the great potential of advanced neuroimaging techniques.

Pharmacogenomic update on multiple sclerosis: a focus on actual and new therapeutic strategies.

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of central nervous system comprising several subtypes. Pharmacological treatment involves only few drugs. Among these, interferon beta (IFN-ß) and glatiramer acetate were the most used. Although evidence supports the efficacy of these agents in treating MS symptoms, actual studies allowed to introduce new innovative drugs in clinical practice. Applying pharmacogenetic approach to MS, IFN-ß and several other immune pathways were abundantly investigated. Numerous reports identified some promising therapy markers but only few markers have emerged as clinically useful. This may be partially due to differences in clinical and methodological criteria in the studies. Indeed, responder and non-responder definitions lack standardized clinical definition. The goal of this review is to treat advances in research on the pharmacogenetic markers of MS drugs and to highlight possible correlations between type of responses and genetic profile, with regard to clinical and methodological discrepancies in the studies.