Relapsing-remitting and secondary-progressive multiple sclerosis patients differ in decoding others' emotions by their eyes.

BACKGROUND AND PURPOSE: Difficulties in emotion processing and social cognition identified in multiple sclerosis (MS) patients have a potential impact on their adaptation to the social environment. We aimed to explore the neural correlates of emotion recognition in MS and possible differences between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) patients by the Reading the Mind in the Eyes test (RMEt). METHODS: A total of 43 MS patients (27 RRMS, 16 SPMS) and 25 matched healthy controls (HC) underwent clinical assessments, RMEt, and a high-resolution T1-weighted 3-T magnetic resonance imaging (MRI) scan. The number of correct answers on the RMEt was compared between groups. T1-weighted volumes were processed according to an optimized voxel-based morphometry (VBM) protocol to obtain gray matter (GM) maps. Voxelwise analyses were run to assess potential associations between RMEt performance and regional GM volumes. RESULTS: Taken altogether, MS patients reported significantly lower performance on the RMEt compared to HC. When dividing the patients into those with RRMS and those with SPMS, only the latter group was found to perform significantly worse than HC on the RMEt. VBM analysis revealed significant association between RMEt scores and GM volumes in several cortical (temporoparieto-occipital cortex) and subcortical (hippocampus, parahippocampus, and basal ganglia) brain regions, and in the cerebellum in SPMS patients only. CONCLUSIONS: Results suggest that, in addition to other clinical differences between RRMS and SPMS, the ability to recognize others' emotional states may be affected in SPMS more significantly than RRMS patients. This is supported by both behavioral and MRI data.

The Italian validation of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS) and the application of the Cognitive Impairment Index scoring procedure in MS patients.

Cognitive dysfunction occurs in almost 50-60% of patients with multiple sclerosis (MS) even in early stages of the disease and affects different aspects of patient's life. Aims of the present study were (1) to introduce and validate an Italian version of the minimal assessment of cognitive functions in MS (MACFIMS) battery and (2) to propose the use of the Cognitive Impairment Index (CII) as a scoring procedure to define the degree of impairment in relapsing-remitting (RRMS) and secondary-progressive (SPMS) patients. A total of 240 HC and 123 MS patients performed the Italian version of the MACFIMS composed by the same tests as the original except for the Paced Auditory Serial Addition Test. The CII was derived for each score of the 11 scales for participants of both groups. The results of the study show that cognitive impairment affects around 50% of our sample of MS patients. In RRMS group, only the 15.7% of patients reported a severe impairment, while in the group of SPMS, the 51.4% of patients felt in the "severely impaired" group. Results are in line with previously reported percentages of impairment in MS patients, showing that the calculation of the CII applied to the Italian version of the MACFIMS is sensitive and reliable in detecting different degrees of impairment in MS patients.

Adverse working events in patients with multiple sclerosis.

Multiple sclerosis (MS) and working status have recently arisen great interest. Fatigue, physical disability, cognition, and psychological disturbances have been linked to unemployment, as well to accidents during daily activities. The aim of our study was to determine frequency of different types of accidents at workplace (AWE) and possible clinical differences among employed (MSe) and unemployed (MSu) MS patients. Sixty MS patients (31 employed, 29 unemployed) and twenty healthy control subjects were recruited. All employed participants were requested to complete an ad-hoc questionnaire to collect AWE and related risks occurring at workplace in the past 2 months. Physical, cognitive, mood, and fatigue evaluations were also assessed. Illness and bumps along with risk of bumps and near falls resulted the most frequent AWE and risks occurring in MSe. Interestingly, those AWE were mostly observed among subjects with anxiety, depression, and cognitive fatigue rather than depending on severity of physical impairment. Moreover, psychological aspects, like anxiety and anger, seemed to play a crucial role in determining AWE. This study provides data on AWE occurrence and suggests possible mechanisms underlying negative events at workplace in MS. This might be important for planning strategies of AWE prevention in MS patients.

[Domestic accidents in patients with multiple sclerosis: proposal and application of questionnaires for their detection]. / Gli incidenti domestici nei pazienti con Sclerosi Multipla: proposta e applicazione di questionari per la loro rilevazione.

OBJECTIVES: Domestic accidents are an important topic as for different viewpoints: for the people that could be victim of them, for the health and economic systems. It could be imagined that people affected by neurological diseases, such as Multiple Sclerosis (MS), could incur into domestic accidents more frequently than people in the general population. Aim of the present work is to introduce a survey's questionnaire for registering occurrence and characteristics of domestic accidents in a population with particular features such as MS patients. METHODS: In 2011, a first edition of this survey questionnaire was already proposed and then applied with a sample of MS patients (QuID). RESULTS: A subsequent newest version of the test (QuID-II) has then been proposed, based on the information collected and on the limits showed by that first edition. CONCLUSIONS: With this new version deepen information can be collected on the characteristics, the biological, environmental and behavioural risk factors for the occurrence of domestic accidents, and this could be useful in planning prevention programs.

Validation of the World Health Organization Disability Assessment Schedule II (WHODAS-II) in patients with multiple sclerosis.

BACKGROUND: The World Health Organization Disability Assessment Schedule (WHODAS-II) is a widely used generic assessment instrument for health and disability. However, a specific psychometric evaluation for this scale in multiple sclerosis (MS) is lacking. This study is aimed at the assessment of the psychometric properties of the WHODAS-II in MS with Cronbach's α and modern Rasch-model analyses. METHODS: The WHODAS-II was administered to 136 consecutively recruited MS patients. Several indexes of fit to the Rasch model were evaluated in order to assess internal construct validity. Internal consistency was assessed with Cronbach's α and the Person Separation Index (PSI). External validity was evaluated by analyzing correlations between the WHODAS-II and the Multiple Sclerosis Quality of Life-54 (MSQoL-54). RESULTS: Classical reliability indexes (Cronbach's α and intraclass correlation) showed good to excellent reliability for most of the subscales and for the total scale (α = 0.93). The total scale both with (36 items) or without (32 items) work items reached good fit to the Rasch model (PSI = 0.83). However, analysis of the subscales could resolve only four subscales out of seven. CONCLUSIONS: The WHODAS-II is a reliable and valid instrument for the assessment of patient-reported disability in MS, with some limitations including some item redundancy and questionable reliability of some subscales.

A survey of the nature of trauma of post-traumatic benign paroxysmal positional vertigo.

OBJECTIVE: A clinical description of post-traumatic benign paroxysmal positional vertigo (t-BPPV) in a large cohort is reported, sometimes caused by apparently insignificant minor head traumas. The aim of the study was to carefully assess the prevalence of t-BPPV and the main outcomes belonging to specific traumatic events. DESIGN: Retrospective analysis of medical records of t-BPPV cases among patients suffering from BPPV. STUDY SAMPLE: Among 3060 patients with a clinical diagnosis of BPPV, we reviewed 716 clinical cases in which a clear association to a traumatic event was present. RESULTS: A traumatic event was identified in 23.4% of total enrolled BPPV patients. Some minor head traumas could be more prone to determine BPPV in females. We confirmed that t-BPPV appeared significantly more difficult to treat than idiopathic form. Posterior canal t-BPPV cases required more treatment sessions before obtaining therapeutic success, while horizontal ones recovered at most after two repositioning maneuvers. CONCLUSION: Post-traumatic BPPV is considered one of the most common known etiologies. An accurate understanding of trauma mechanism, gender prevalence, and therapeutic success rates of each event, could be useful in adequately treating and planning follow-up examinations.

Hedonic tone and its mood and cognitive correlates in Parkinson's disease.

BACKGROUND: Anhedonia has been mainly reported as a symptom of depression and cognitive impairment in Parkinson's disease (PD) patients. Here, we investigated whether hedonic tone depends on depression and clarified its relationship with the cognitive performance of PD patients with different mood disorders. METHODS: In 254 patients, we assessed hedonic tone using the Snaith-Hamilton Pleasure Scale, depression severity using the Beck Depression Inventory, and cognitive performances using the Mental Deterioration Battery. A structural psychiatric interview was used to diagnose major depressive disorder (MDD) and minor depressive disorder (MIND), according to the DSM-IV-TR criteria. RESULTS: PD patients with diagnosis of MDD were more anhedonic than those with MIND and those without depressive disorders. Reduced hedonic tone correlated with depression severity in patients with MDD and no depressive disorders. In multivariate models that consider depression severity and cognitive performances together, anhedonia was related to increased depression severity and episodic memory (auditory-verbal learning) impairment, in patients with MDD and with increased depression severity and attention impairment in patients with no depressive disorders. In patients with MIND, anhedonia did not correlate with depression severity or any cognitive performance score. DISCUSSION: Our findings suggest that anhedonia is related to depression severity and specific cognitive performances in patients with MDD and with no depressive disorder. By contrast, the reduced hedonic tone in patients with MIND is independent from depression severity and cognition. Thus, anhedonia in PD is a heterogeneous and multidimensional phenomenon and require investigation at different levels.

Locus Coeruleus Dysfunction and Trigeminal Mesencephalic Nucleus Degeneration: A Cue for Periodontal Infection Mediated Damage in Alzheimer's Disease?

Alzheimer's disease (AD) is a leading neurodegenerative disease with deteriorating cognition as its main clinical sign. In addition to the clinical history, it is characterized by the presence of two neuropathological hallmark lesions; amyloid-beta (Aß) and neurofibrillary tangles (NFTs), identified in the brain at post-mortem in specific anatomical areas. Recently, it was discovered that NFTs occur initially in the subcortical nuclei, such as the locus coeruleus in the pons, and are said to spread from there to the cerebral cortices and the hippocampus. This contrasts with the prior acceptance of their neuropathology in the enthorinal cortex and the hippocampus. The Braak staging system places the accumulation of phosphorylated tau (p-tau) binding to NFTs in the locus coeruleus and other subcortical nuclei to precede stages I-IV. The locus coeruleus plays diverse psychological and physiological roles within the human body including rapid eye movement sleep disorder, schizophrenia, anxiety, and depression, regulation of sleep-wake cycles, attention, memory, mood, and behavior, which correlates with AD clinical behavior. In addition, the locus coeruleus regulates cardiovascular, respiratory, and gastrointestinal activities, which have only recently been associated with AD by modern day research enabling the wider understanding of AD development via comorbidities and microbial dysbiosis. The focus of this narrative review is to explore the modes of neurodegeneration taking place in the locus coeruleus during the natural aging process of the trigeminal nerve connections from the teeth and microbial dysbiosis, and to postulate a pathogenetic mechanism due to periodontal damage and/or infection focused on Treponema denticola.

Treponema denticola Has the Potential to Cause Neurodegeneration in the Midbrain via the Periodontal Route of Infection-Narrative Review.

Alzheimer's disease (AD) is a neurodegenerative disease and the most common example of dementia. The neuropathological features of AD are the abnormal deposition of extracellular amyloid-ß (Aß) and intraneuronal neurofibrillary tangles with hyperphosphorylated tau protein. It is recognized that AD starts in the frontal cerebral cortex, and then it progresses to the entorhinal cortex, the hippocampus, and the rest of the brain. However, some studies on animals suggest that AD could also progress in the reverse order starting from the midbrain and then spreading to the frontal cortex. Spirochetes are neurotrophic: From a peripheral route of infection, they can reach the brain via the midbrain. Their direct and indirect effect via the interaction of their virulence factors and the microglia potentially leads to the host peripheral nerve, the midbrain (especially the locus coeruleus), and cortical damage. On this basis, this review aims to discuss the hypothesis of the ability of Treponema denticola to damage the peripheral axons in the periodontal ligament, to evade the complemental pathway and microglial immune response, to determine the cytoskeletal impairment and therefore causing the axonal transport disruption, an altered mitochondrial migration and the consequent neuronal apoptosis. Further insights about the central neurodegeneration mechanism and Treponema denticola's resistance to the immune response when aggregated in biofilm and its quorum sensing are suggested as a pathogenetic model for the advanced stages of AD.

Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson's disease.

BACKGROUND: Alterations in blood-brain barrier permeability have been proposed to represent a relevant factor contributing to Parkinson's disease progression. However, few studies have addressed this issue in patients at different stages of disease. METHODS: Albumin was measured in cerebrospinal fluid and serum samples obtained from 73 non-demented subjects with idiopathic Parkinson's disease and 47 age-matched control subjects. The albumin ratio (AR) was calculated to assess blood-cerebrospinal fluid and blood-brain barrier function. The group of patients with Parkinson's disease included 46 subjects with Hoehn-Yahr staging between 1 and 2 and 27, with a score ranging from 2.5 to 4. RESULTS: Statistically significant differences in albumin ratio were found between patients with advanced disease, and both early-stage and unaffected groups. Conversely, early-phase patients did not differ from healthy subjects. Additionally, dopaminergic treatment seems to exert a possible effect on AR values. CONCLUSIONS: Our study demonstrates that possible dysfunction of the blood-cerebrospinal fluid barrier, blood-brain barrier, or both, characterize Parkinson's disease progression. The associations between clinical scores, treatments and biochemical findings suggest a progressive impairment of barrier integrity during the course of the disease.

The impact of rotigotine on cardiovascular autonomic function in early Parkinson's disease.

Dysautonomia can occur in early stages of Parkinson's disease (PD) influencing tolerance to dopaminergic therapies. Rotigotine, a non-ergot dopamine agonist, has recently been developed as an effective alternative antiparkinsonian drug, but its influence on the autonomic nervous system was not investigated. Twenty subjects out of 34 consecutive de novo PD patients were submitted to full assessment of cardiovascular autonomic function before and after reaching a stable rotigotine regimen [6 mg/24 h (n = 3) or 8 mg/24 h (n = 17)]. Patients reached significant clinical improvement (-27% on the Unified Parkinson's Disease Rating Scale part III) and did not show significant differences in cardiovascular tests compared to baseline data. However, an unexpected trend towards increasing systolic blood pressure after head-up tilt test was detected. Our study demonstrates that rotigotine does not influence cardiovascular autonomic responses in early de novo PD patients. Consequently, it may represent a well-tolerated and efficacious therapeutic option in newly diagnosed PD subjects.

The Mechanistic Pathways of Periodontal Pathogens Entering the Brain: The Potential Role of Treponema denticola in Tracing Alzheimer's Disease Pathology.

Alzheimer's Disease (AD) is a complex neurodegenerative disease and remains the most common form of dementia. The pathological features include amyloid (Aß) accumulation, neurofibrillary tangles (NFTs), neural and synaptic loss, microglial cell activation, and an increased blood-brain barrier permeability. One longstanding hypothesis suggests that a microbial etiology is key to AD initiation. Among the various periodontal microorganisms, Porphyromonas gingivalis has been considered the keystone agent to potentially correlate with AD, due to its influence on systemic inflammation. P. gingivalis together with Treponema denticola and Tannerella forsythia belong to the red complex consortium of bacteria advocated to sustain periodontitis within a local dysbiosis and a host response alteration. Since the implication of P. gingivalis in the pathogenesis of AD, evidence has emerged of T. denticola clusters in some AD brain tissue sections. This narrative review explored the potential mode of spirochetes entry into the AD brain for tracing pathology. Spirochetes are slow-growing bacteria, which can hide within ganglia for many years. It is this feature in combination with the ability of these bacteria to evade the hosts' immune responses that may account for a long lag phase between infection and plausible AD disease symptoms. As the locus coeruleus has direct connection between the trigeminal nuclei to periodontal free nerve endings and proprioceptors with the central nervous system, it is plausible that they could initiate AD pathology from this anatomical region.

Homeostatic changes of the endocannabinoid system in Parkinson's disease.

Endocannabinoids (eCBs) are endogenous lipids that bind principally type-1 and type-2 cannabinoid (CB(1) and CB(2)) receptors. N-Arachidonoylethanolamine (AEA, anandamide) and 2-arachidonoylglycerol (2-AG) are the best characterized eCBs that are released from membrane phospholipid precursors through multiple biosynthetic pathways. Together with their receptors and metabolic enzymes, eCBs form the so-called "eCB system". The later has been involved in a wide variety of actions, including modulation of basal ganglia function. Consistently, both eCB levels and CB(1) receptor expression are high in several basal ganglia regions, and more specifically in the striatum and in its target projection areas. In these regions, the eCB system establishes a close functional interaction with dopaminergic neurotransmission, supporting a relevant role for eCBs in the control of voluntary movements. Accordingly, compelling experimental and clinical evidence suggests that a profound rearrangement of the eCB system in the basal ganglia follows dopamine depletion, as it occurs in Parkinson's disease (PD). In this article, we provide a brief survey of the evidence that the eCB system changes in both animal models of, and patients suffering from, PD. A striking convergence of findings is observed between both rodent and primate models and PD patients, indicating that the eCB system undergoes dynamic, adaptive changes, aimed at restoring an apparent homeostasis within the basal ganglia network.

Dual-Task Performance in Multiple Sclerosis' Patients: Cerebellum Matters?

OBJECTIVE: Gait, cognitive impairments, and their mutual influence in dual tasking (cognitive-motor dual tasking, CM-DT) are important to address therapeutic approaches in patients with multiple sclerosis (PMS). CM-DT correlates have been widely investigated with variable and dissimilar results, due to differences in methods. However, although the cerebellum has recently shown to be involved in both motor and cognitive functions, few studies have explored its role in the integration of the concurrent execution of gait and cognition. This case-control study aims to explore the effects of adding a cognitive task to walking in PMS and to investigate the role of the cerebellum in the interfering process. METHODS: In total, 20 patients and 18 healthy controls (HC) underwent clinical assessments, dual task (DT), and 3 T magnetic resonance imaging (MRI). DT was composed by three 2-min trials requiring fast walking. In 2 of them 2 different cognitive tasks were added. RESULTS: Both groups evidenced the presence of cognitive-motor interference (CMI) for both cognitive conditions with a greater effect of word list generation task in PMS. Analysis of variance between HC and patients with high or low performances showed a significantly increased volume in Vermis lobules VIIIa and IX of high performers compared with HC. CONCLUSION: Our results show that CMI is also present in healthy individuals but is significantly more disabling in PMS. Furthermore, MRI data point to the existence of an initial mechanism of cerebellar reorganization in PMS with lower interference. Subsequently, the failure of this mechanism due to the progression of disability leads to a more evident expression of symptoms.

Dynamic changes of anandamide in the cerebrospinal fluid of Parkinson's disease patients.

A correct balance between endocannabinoid and dopamine-dependent systems is believed to underlie physiological motor control. We measured the levels of the endocannabinoid anandamide in the cerebrospinal fluid of Parkinson's disease (PD) patients. Subjects were divided into three groups: newly diagnosed de novo patients, subjects undergoing drug withdrawal, and patients under pharmacological therapy. These groups were compared to age-matched control subjects. Anandamide levels in untreated patients were more than doubled as compared to controls. However, chronic dopaminergic replacement restored control anandamide levels. Abnormal anandamide increase might reflect a compensatory mechanism occurring in course of PD, aimed at normalizing dopamine depletion.

Can personality traits influence occupational stress in multiple sclerosis patients? A one-year longitudinal study.

Recent studies suggest that patients with Multiple Sclerosis (MS) might be at risk of unemployment due to physical and psychological symptoms. Furthermore, MS patients appear to be more exposed to a higher level of occupational stress, which might be linked to some personality characteristics. Our aim was to ascertain, by means of a longitudinal study, whether changes in occupational stress can be predicted by some personality traits, which could thereby become potential targets of therapeutic interventions. This study describes the longitudinal results of a previous work on occupational stress and personality traits in MS patients. Twenty MS patients were reevaluated one year after the baseline assessment. The statistical comparison between the baseline and follow-up visits showed a significant change in the scores on some Occupational Stress Inventory (OSI) subscales-Locus of control total (LOC-tot) and Involvement coping strategies (CI). While Neuroticism and Openness might predict changes in LOC-tot, Conscientiousness appeared to be important in the development of CI at one year. The findings indicate that certain personality traits can influence some longitudinal changes in occupational stress, thus making them useful in predicting stress at workplace.

Long-term treatment with rotigotine in drug-naïve PSP patients.

Progressive supranuclear palsy (PSP) is a severe neurodegenerative disease still lacking of alleviating treatments for either cognitive or motor disturbances. Aimed at widening the spectrum of therapeutic options, here, we describe efficacy and safety of a long-term treatment with Rotigotine, a non-ergolinic dopamine agonist, in PSP. Seven PSP drug-naïve patients, presenting with Richardson's syndrome, received up to 6 mg/24 h transdermal patch for 42 weeks as unique therapy. Adverse effects were recorded; efficacy was measured by comparing baseline and final treatment scores of Montreal Cognitive Assessment (MoCA), Unified Parkinson Disease Rating Scale part3, and PSP rating scale (PSP-RS). At the end of our observation, no significant adverse events occurred; the cognitive item of PSP-RS was improved and MoCA score was similar at baseline. Contrariwise, motor disturbances worsened according to disease progression. Our observation thus suggests that long-term treatment with low doses of rotigotine is well tolerated and may support cognitive functions of PSP patients.

Disruption of neurite morphology parallels MS progression.

OBJECTIVES: To apply advanced diffusion MRI methods to the study of normal-appearing brain tissue in MS and examine their correlation with measures of clinical disability. METHODS: A multi-compartment model of diffusion MRI called neurite orientation dispersion and density imaging (NODDI) was used to study 20 patients with relapsing-remitting MS (RRMS), 15 with secondary progressive MS (SPMS), and 20 healthy controls. Maps of NODDI were analyzed voxel-wise to assess the presence of abnormalities within the normal-appearing brain tissue and the association with disease severity. Standard diffusion tensor imaging (DTI) parameters were also computed for comparing the 2 techniques. RESULTS: Patients with MS showed reduced neurite density index (NDI) and increased orientation dispersion index (ODI) compared with controls in several brain areas (p < 0.05), with patients with SPMS having more widespread abnormalities. DTI indices were also sensitive to some changes. In addition, patients with SPMS showed reduced ODI in the thalamus and caudate nucleus. These abnormalities were associated with scores of disease severity (p < 0.05). The association with the MS functional composite score was higher in patients with SPMS compared with patients with RRMS. CONCLUSIONS: NODDI and DTI findings are largely overlapping. Nevertheless, NODDI helps interpret previous findings of increased anisotropy in the thalamus of patients with MS and are consistent with the degeneration of selective axon populations.

A more in-depth interpretation of MMPI-2 in MS patients by using Harris and Lingoes subscales.

Multiple Sclerosis (MS) is frequently associated with neuropsychiatric abnormalities. The aim of our study was to discriminate between psychosomatic disturbances and MS physically-related symptoms using the Harris-Lingoes subscales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Forty-six MS out-patients (35 females; mean age = 44.5); and 82 healthy volunteers (62 females; mean age = 46.5) were evaluated with MMPI-2 questionnaire. The frequency distribution of MMPI-2 clinical scales with high scores (> = 65) and the related Harris-Lingoes subscales were analyzed for both MS patients and healthy control subjects. Data analysis showed elevated scores in 47.8% of the patients mainly on MMPI-2 clinical scales 1, 2, and 3. The Harris-Lingoes subscales analysis allowed us to isolate and identify physical symptoms contributing to elevation of MMPI-2 clinical scales, reduce the occurrence of false positives (MMPI-2 clinical scales elevations mainly due to MS physical disability) and provide a more detailed description of psycho-emotional symptoms of MS patients. In conclusion, our study shows the utility of Harris-Lingoes subscales analysis when MMPI-2 is used for psychological assessment of MS patients.