Using illusions to understand hallucinations: differences in perceptual performances on illusory figures may underscore specific visuoperceptual impairments in Parkinson's disease.

Visual hallucinations are prevalent, potentially disabling symptoms of Parkinson's Disease. Multiple impairments in bottom-up sensory processing and top-down perceptual modulation are implicated in the pathophysiology of these phenomena. In healthy individuals, visual illusions are elicited by illusory figures through parametric manipulations of geometrical configurations, contrast, color, or spatial relationships between stimuli. These illusory percepts provide insight on the physiologic processes subserving conscious and unconscious perception. In this exploratory, cross-sectional, controlled study, perceptual performance on illusory figures was assessed on 11 PD patients with hallucinations, 10 non-hallucinating PD patients, and 10 age-matched healthy individuals. In order to characterize potential neural substrates of perceptual performances, patients' brain metabolic patterns on FDG PET were also analyzed. Illusions relying on attentional modulation and global perception were attenuated in PD patients without hallucinations. This pattern was no longer recognizable in hallucinating patients. Conversely, illusory effects normally counteracted by figure to background segregation and overlapping figures recognition were enhanced in PD patients with hallucinations. FDG PET findings further suggest that perceptual differences between PD patients might be linked to abnormal top-down perceptual modulation.

Neuromuscular assessment of force development, postural, and gait performance under cognitive-motor dual-tasking in healthy older adults and people with early Parkinson's disease: Study protocol for a cross-sectional Mobile Brain/Body Imaging (MoBI) study.

Background: Neuromuscular dysfunction is common in older adults and more pronounced in neurodegenerative diseases. In Parkinson's disease (PD), a complex set of factors often prevents the effective performance of activities of daily living that require intact and simultaneous performance of the motor and cognitive tasks. Methods: The cross-sectional study includes a multifactorial mixed-measure design. Between-subject factor grouping the sample will be Parkinson's Disease (early PD vs. healthy). The within-subject factors will be the task complexity (single- vs. dual-task) in each motor activity, i.e., overground walking, semi-tandem stance, and isometric knee extension, and a walking condition (wide vs. narrow lane) will be implemented for the overground walking activity only. To study dual-task (DT) effects, in each motor activity participants will be given a secondary cognitive task, i.e., a visual discrimination task for the overground walking, an attention task for the semi-tandem, and mental arithmetic for the isometric extension. Analyses of DT effects and underlying neuronal correlates will focus on both gait and cognitive performance where applicable. Based on an a priori sample size calculation, a total N = 42 older adults (55-75 years) will be recruited. Disease-specific changes such as laterality in motor unit behavior and cortical control of movement will be studied with high-density surface electromyography and electroencephalography during static and dynamic motor activities, together with whole-body kinematics. Discussion: This study will be one of the first to holistically address early PD neurophysiological and neuromuscular patterns in an ecologically valid environment under cognitive-motor DT conditions of different complexities. The outcomes of the study aim to identify the biomarker for early PD either at the electrophysiological, muscular or kinematic level or in the communication between these systems. Clinical Trial Registration: ClinicalTrials.Gov, NCT05477654. This study was approved by the Medical Ethical Committee (106/2021).

Olfactory swab sampling optimization for α-synuclein aggregate detection in patients with Parkinson's disease.

BACKGROUND: In patients with Parkinson's disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not as accurate as in other α-synucleinopathies. It is unknown whether these variable results might be related to a different distribution of pathological α-syn in OM. Thus, we investigated whether nasal swab (NS) performed in areas with a different coverage by olfactory neuroepithelium, such as agger nasi (AN) and middle turbinate (MT), might affect the detection of pathological α-syn. METHODS: NS was performed in 66 patients with PD and 29 non-PD between September 2018 and April 2021. In 43 patients, cerebrospinal fluid (CSF) was also obtained and all samples were analyzed by RT-QuIC for α-syn. RESULTS: In the first round, 72 OM samples were collected by NS, from AN (NSAN) or from MT (NSMT), and 35 resulted positive for α-syn RT-QuIC, including 27/32 (84%) from AN, 5/11 (45%) from MT, and 3/29 (10%) belonging to the non-PD patients. Furthermore, 23 additional PD patients underwent NS at both AN and MT, and RT-QuIC revealed α-syn positive in 18/23 (78%) NSAN samples and in 10/23 (44%) NSMT samples. Immunocytochemistry of NS preparations showed a higher representation of olfactory neural cells in NSAN compared to NSMT. We also observed α-syn and phospho-α-syn deposits in NS from PD patients but not in controls. Finally, RT-QuIC was positive in 22/24 CSF samples from PD patients (92%) and in 1/19 non-PD. CONCLUSION: In PD patients, RT-QuIC sensitivity is significantly increased (from 45% to 84%) when NS is performed at AN, indicating that α-syn aggregates are preferentially detected in olfactory areas with higher concentration of olfactory neurons. Although RT-QuIC analysis of CSF showed a higher diagnostic accuracy compared to NS, due to the non-invasiveness, NS might be considered as an ancillary procedure for PD diagnosis.

Brain oscillatory patterns in mild cognitive impairment due to Alzheimer's and Parkinson's disease: An exploratory high-density EEG study.

OBJECTIVE: We investigated brain cortical activity alterations, using a resting-state 256-channel high-density EEG (hd-EEG), in Alzheimer's (AD) and Parkinson's (PD) disease subjects with mild cognitive impairment (MCI) and correlations between quantitative spectral EEG parameters and the global cognitive status assessed by Montreal Cognitive Assessment (MoCA) score. METHODS: Fifteen AD-MCI, eleven PD-MCI and ten age-matched healthy-controls (HC) underwent hd-EEG recordings and neuropsychological assessment. Cerebrospinal fluid biomarker analysis was performed to obtain well-characterized groups. EEG spectral features were extracted and the differences between the three groups, as well as correlations with MoCA, were investigated. RESULTS: The results showed significantly lower alpha2 power and alpha2/alpha1 ratio in both AD-MCI and PD-MCI compared to controls. The significantly higher theta and lower beta power and alpha/theta ratio were observed in PD-MCI compared to AD-MCI and HC. MoCA score correlated inversely with theta power and directly with alpha2 and beta powers, as well as with alpha2/alpha1 and alpha/theta ratios. CONCLUSIONS: This study highlighted significant differences in EEG patterns in AD-MCI and PD-MCI patients and remarked the role of EEG parameters as possible surrogate markers of cognitive status in both neurodegenerative diseases. SIGNIFICANCE: In addition to well-established biomarkers, our findings could support early detection of cognitive dysfunction in neurodegenerative disorders and could help to monitor disease progression and therapeutic responses.

Comprehensive telemedicine solution for remote monitoring of Parkinson's disease patients with orthostatic hypotension during COVID-19 pandemic.

OBJECTIVE: Orthostatic hypotension (OH) represents a frequent but under-recognized phenomenon in Parkinson's disease (PD). During COVID-19 pandemic, Information and Communication Technologies (ICT) have become pivotal in the management of chronic diseases like PD, not only to assess motor impairment, but also for vital signs monitoring. This pilot study aimed to propose a real-time remote home-monitoring system and protocol for PD patients with OH. METHODS: Vital parameters were acquired by wireless devices and transmitted to an ICT platform, providing data and smart notifications to the healthcare provider through an interactive web portal. Eight patients with idiopathic PD and OH underwent 5-day monitoring. Data about OH episodes, therapeutic interventions, impact on daily activities, and patient satisfaction were collected and analyzed. RESULTS: The proposed solution allowed the identification of 65 OH episodes and subsequent medical interventions. Thirty-five episodes were asymptomatic, especially in the postprandial and in the afternoon recordings. Systolic-blood-pressure (SBP) and diastolic-blood-pressure (DBP) were significantly lower in symptomatic episodes, while the pressure drops resulted significantly higher in presence of symptoms. High usability and patient satisfaction scores were observed. CONCLUSION: The proposed home-monitoring system and protocol have proved to provide useful information and to allow prompt interventions in the management of PD patients with OH during COVID-19 pandemic.

Paraneoplastic neurological syndromes associated with non-Hodgkin lymphoma: a case series.

BACKGROUND: Paraneoplastic neurological syndromes (PNS) associated with lymphoma are rare diseases that usually have different peculiar features when compared to PNS associated with solid neoplasms. METHODS: We retrospectively identified patients with NHL-associated PNS. Clinical and demographic data are reported. RESULTS: We report two cases of NHL-associated PNS: a 72-years old female that presented with rapidly progressive cerebellar syndrome (RCPS) and a 65-years old male that presented with encephalomyelitis (confusion, sensory neuropathy, lower motor neuron involvement). Both PNS were associated with a NHL, small lymphocytic lymphoma and nodal marginal zone lymphoma respectively, and onconeural antibodies tested negative. All patients received first-line immunotherapy with absent or minimal benefit and died of intercurrent infection before cancer or immunosuppressive treatment. DISCUSSION: RCPS and encephalomyelitis rarely present in association with NHL. In our cases, those syndromes took place in the setting of non-aggressive advanced hematological disorders, had an unfavorable prognosis with minimal benefit from immunotherapy, and were seronegative for onconeural antibodies. Our patients fulfilled the criteria for "definite PNS" in the 2004 PNS criteria, but they would be classified as "probable", in the new 2021 PNS criteria. The newest criteria rely on onconeural antibodies testing and on the evidence of antigen expression in cancer cells, features that are usually absent in NHL-associated PNS. New antibodies are being discovered but are still not available to promptly test yet. CONCLUSION: NHL-associated PNS are rare and bear unfavorable prognosis. The diagnosis should not be overlooked even in seronegative patients.

Effects of tDCS on reward responsiveness and valuation in Parkinson's patients with impulse control disorders.

Parkinson's disease (PD) patients with impulse control disorders (ICD) frequently report hypersensitivity to rewards. However, a few studies have explored the effectiveness of modulation techniques on symptoms experienced by these patients. In this study, we assessed the effect of anodal tDCS over the DLPFC on reward responsiveness and valuation in PD patients with ICD. 43 participants (15 PD patients with ICD, 13 PD without ICD, and 15 healthy matched controls) were asked to perform a reward-craving test employing both explicit (self-ratings of liking and wanting) and implicit (heart rate and skin conductance response) measures, as well as two temporal discounting tasks with food and money rewards. Each participant performed the experimental tasks during active anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC), anodal tDCS of the primary motor cortex (M1), and sham tDCS. Results showed increased wanting and a steeper temporal discounting of rewards in PD with ICD compared to the other groups. Moreover, we found that PD without ICD exhibit reduced liking for rewards. tDCS results capable to modulate the altered intensity of PD patients' liking, but not wanting and temporal discounting of rewards in PD patients with ICD. These findings confirm that alterations in reward responsiveness and valuation are characteristics of impulse control disorders in patients with PD but suggest that anodal tDCS over the left DLPFC is not capable to influence these processes. At the same time, they provide new insight into affective experience of rewards in PD.

123I-Metaiodobenzylguanidine Myocardial Scintigraphy in Discriminating Degenerative Parkinsonisms.

BACKGROUND: 123I-Metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy is a useful technique to differentiate Parkinson's disease (PD) from atypical parkinsonisms, since it is generally abnormal in PD and normal in the latter. Reduction of myocardial MIBG uptake is a supportive feature in the latest PD diagnostic criteria. OBJECTIVES: To explore the clinical contribution of myocardial scintigraphy in discriminating different forms of parkinsonisms, especially when atypical features are present. METHODS: Forty-one patients with parkinsonism underwent a 123I-MIBG myocardial scintigraphy in our Movement Disorders Center. Disease evolution was reviewed by applying the latest disease criteria for PD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), as appropriate. Three diagnostic times were defined: T1 (before scintigraphy execution), T2 (immediately after the exam) and T3 (two years later). Early and delayed heart/mediastinum (H/M) ratios and washout rate (WR) were analyzed. RESULTS: Myocardial scintigraphy showed impaired MIBG uptake in 12 out of 15 patients with a definite PD diagnosis, while normal uptake was found in 20 of 26 patients with no-PD. Early and delayed H/M ratios were significantly lower in PD compared to overall no-PD patients and MSA patients. 123I-MIBG myocardial scintigraphy was abnormal in all PD patients with dysautonomia. After 123I-MIBG myocardial scintigraphy (T2), in 9 patients (22%) an improvement of diagnostic accuracy was reached. CONCLUSIONS: Diagnostic accuracy of myocardial scintigraphy in distinguishing PD from atypical parkinsonism was suboptimal. Nevertheless, this study confirmed the relevance of 123I-MIBG myocardial scintigraphy for the discrimination of PD from atypical parkinsonism, especially when dysautonomic symptoms are present.

Alpha-synuclein seeds in olfactory mucosa and cerebrospinal fluid of patients with dementia with Lewy bodies.

In patients with suspected dementia with Lewy bodies, the detection of the disease-associated α-synuclein in easily accessible tissues amenable to be collected using minimally invasive procedures remains a major diagnostic challenge. This approach has the potential to take advantage of modern molecular assays for the diagnosis of α-synucleinopathy and, in turn, to optimize the recruitment and selection of patients in clinical trials, using drugs directed at counteracting α-synuclein aggregation. In this study, we explored the diagnostic accuracy of α-synuclein real-time quaking-induced conversion assay by testing olfactory mucosa and CSF in patients with a clinical diagnosis of probable (n = 32) or prodromal (n = 5) dementia with Lewy bodies or mixed degenerative dementia (dementia with Lewy bodies/Alzheimer's disease) (n = 6). Thirty-eight patients with non-α-synuclein-related neurodegenerative and non-neurodegenerative disorders, including Alzheimer's disease (n = 10), sporadic Creutzfeldt-Jakob disease (n = 10), progressive supranuclear palsy (n = 8), corticobasal syndrome (n = 1), fronto-temporal dementia (n = 3) and other neurological conditions (n = 6) were also included, as controls. All 81 patients underwent olfactory swabbing while CSF was obtained in 48 participants. At the initial blinded screening of olfactory mucosa samples, 38 out of 81 resulted positive while CSF was positive in 19 samples out of 48 analysed. After unblinding of the results, 27 positive olfactory mucosa were assigned to patients with probable dementia with Lewy bodies, five with prodromal dementia with Lewy bodies and three to patients with mixed dementia, as opposed to three out 38 controls. Corresponding results of CSF testing disclosed 10 out 10 positive samples in patients with probable dementia with Lewy bodies and six out of six with mixed dementia, in addition to three out of 32 for controls. The accuracy among results of real-time quaking-induced conversion assays and clinical diagnoses was 86.4% in the case of olfactory mucosa and 93.8% for CSF. For the first time, we showed that α-synuclein real-time quaking-induced conversion assay detects α-synuclein aggregates in olfactory mucosa of patients with dementia with Lewy bodies and with mixed dementia. Additionally, we provided preliminary evidence that the combined testing of olfactory mucosa and CSF raised the concordance with clinical diagnosis potentially to 100%. Our results suggest that nasal swabbing might be considered as a first-line screening procedure in patients with a diagnosis of suspected dementia with Lewy bodies followed by CSF analysis, as a confirmatory test, when the result in the olfactory mucosa is incongruent with the initial clinical diagnosis.

Efficacy of rituximab on seizure control and cognitive symptoms in leucine-rich, glioma-inactivated 1 (LGI1) limbic encephalitis: a high-density electroencephalography case study.

LGI1 encephalitis is an autoimmune disorder characterized by cognitive symptoms and seizures, which rarely respond to common antiepileptic drugs (AEDs). Rituximab (RTX) is a CD-20-depleting monoclonal antibody which has been used for the treatment of LGI1 encephalitis, however, its efficacy remains controversial. A 54-year-old woman came to our attention due to memory loss and gambling. Brain MRI revealed areas of bilateral hippocampal hyperintensity and LGI1 antibodies were found in both serum and cerebrospinal fluid. Immunotherapy with steroids was started, followed by intravenous immunoglobulins with partial improvement. The patient developed multiple generalized tonic-clonic seizures. She was then administered intravenous rituximab with significant improvement for both cognitive symptoms and seizure control. High-density EEG was recorded before treatment, seven days after the first dose and seven days after the second dose. Topoplot and power spectrum analysis were performed for each recording. Interictal epileptiform discharges, as well as theta power bands, were significantly reduced after each dose, while topoplot analysis showed reduced spreading over posterior and frontal electrodes for interictal epileptiform discharges of temporal origin. Our experience indicates that rituximab is a valid treatment for LGI1 encephalitis, demonstrating efficacy for both cognitive symptoms and seizure control. High-density EEG could represent a novel, safe and reproducible method to study epileptogenesis in autoimmune limbic encephalitis.

Action observation improves sit-to-walk in patients with Parkinson's disease and freezing of gait. Biomechanical analysis of performance.

INTRODUCTION: Freezing of gait (FoG) is one of the most disabling gait disorders in Parkinson's disease (PD), reflecting motor and cognitive impairments, mainly related to dopamine deficiency. Recent studies investigating kinematic and kinetic factors affecting gait in these patients showed a postural instability characterized by disturbed weight-shifting, inappropriate anticipatory postural adjustment, worse reactive postural control, and a difficulty executing complex motor tasks (i.e. sit-to-walk). These symptoms are difficult to alleviate and not very responsive to Levodopa. For this reason, additional therapeutic actions based on specific therapeutic protocols may help patients with their daily lives. We conducted a randomized control trial aimed to test if two clinical protocols for PD patients with FoG were effective to improve postural control. METHODS: Rehabilitation protocols, conceived to improve gait, were based on learning motor exercises with the Action Observation plus Sonification (AOS) technique, or by the use of external sensory cues. We collected biomechanical data (Center of Mass COM, Center of Pressure COP, and moving timings), using the sit-to-walk task as a measure of motor and gait performance. RESULTS: Kinetic and kinematic data showed that when treatment effects consolidate, patients treated with AOS protocol are more efficient in merging subsequent motor tasks (sit-to-stand and gait initiation), and diminished the total moving time and the area of the COP positions. CONCLUSION: We demonstrated for the first time that PD patients with FoG treated with an AOS protocol aimed at relearning appropriate gait patterns increased balance control and re-acquired more efficient postural control.

Does the Degree of Trunk Bending Predict Patient Disability, Motor Impairment, Falls, and Back Pain in Parkinson's Disease?

Background: Postural abnormalities in Parkinson's disease (PD) form a spectrum of functional trunk misalignment, ranging from a "typical" parkinsonian stooped posture to progressively greater degrees of spine deviation. Objective: To analyze the association between degree of postural abnormalities and disability and to determine cut-off values of trunk bending associated with limitations in activities of daily living (ADLs), motor impairment, falls, and back pain. Methods: The study population was 283 PD patients with ≥5° of forward trunk bending (FTB), lateral trunk bending (LTB) or forward neck bending (FNB). The degrees were calculated using a wall goniometer (WG) and software-based measurements (SBM). Logistic regression models were used to identify the degree of bending associated with moderate/severe limitation in ADLs (Movement Disorders Society Unified PD Rating Scale [MDS-UPDRS] part II ≥17), moderate/severe motor impairment (MDS-UPDRS part III ≥33), history of falls (≥1), and moderate/severe back pain intensity (numeric rating scale ≥4). The optimal cut-off was identified using receiver operating characteristic (ROC) curves. Results: We found significant associations between modified Hoehn & Yahr stage, disease duration, sex, and limitation in ADLs, motor impairment, back pain intensity, and history of falls. Degree of trunk bending was associated only with motor impairment in LTB (odds ratio [OR] 1.12; 95% confidence interval [CI], 1.03-1.22). ROC curves showed that patients with LTB of 10.5° (SBM, AUC 0.626) may have moderate/severe motor impairment. Conclusions: The severity of trunk misalignment does not fully explain limitation in ADLs, motor impairment, falls, and back pain. Multiple factors possibly related to an aggressive PD phenotype may account for disability in PD patients with FTB, LTB, and FNB.

A human minisatellite hosts an alternative transcription start site for NPRL3 driving its expression in a repeat number-dependent manner.

Minisatellites, also called variable number of tandem repeats (VNTRs), are a class of repetitive elements that may affect gene expression at multiple levels and have been correlated to disease. Their identification and role as expression quantitative trait loci (eQTL) have been limited by their absence in comparative genomic hybridization and single nucleotide polymorphisms arrays. By taking advantage of cap analysis of gene expression (CAGE), we describe a new example of a minisatellite hosting a transcription start site (TSS) which expression is dependent on the repeat number. It is located in the third intron of the gene nitrogen permease regulator like protein 3 (NPRL3). NPRL3 is a component of the GAP activity toward rags 1 protein complex that inhibits mammalian target of rapamycin complex 1 (mTORC1) activity and it is found mutated in familial focal cortical dysplasia and familial focal epilepsy. CAGE tags represent an alternative TSS identifying TAGNPRL3 messenger RNAs (mRNAs). TAGNPRL3 is expressed in red blood cells both at mRNA and protein levels, it interacts with its protein partner NPRL2 and its overexpression inhibits cell proliferation. This study provides an example of a minisatellite that is both a TSS and an eQTL as well as identifies a new VNTR that may modify mTORC1 activity.

Postural Abnormalities in Parkinson's Disease: An Epidemiological and Clinical Multicenter Study.

INTRODUCTION: The overall frequency of postural abnormalities (PA) in Parkinson's disease (PD) is unknown. We evaluated the overall prevalence of PA and assessed the association with demographic and clinical variables. METHODS: For this multicenter, cross-sectional study, consecutive PD outpatients attending 7 tertiary Italian centers were enrolled. Patients were evaluated and compared for the presence of isolated PA such as camptocormia, Pisa syndrome, and anterocollis and for combined forms (ie, camptocormia + Pisa syndrome) together with demographic and clinical variables. RESULTS: Of the total 811 PD patients enrolled, 174 (21.5%; 95% confidence interval [CI], 18.6%-24.3%) presented PA, 144 of which had isolated PA and 30 had combined PA. The prevalence of camptocormia was 11.2% (95% CI, 9%-13.3%), Pisa syndrome 8% (95% CI, 6.2%-9.9%), and anterocollis 6.5% (95% CI, 4.9%-8.3%). Patients with PA were more often male and older with longer disease duration, more advanced disease stage, more severe PD symptoms, a bradykinetic/rigid phenotype, and poorer quality of life. They were initially treated with levodopa, and more likely to be treated with a combination of levodopa and dopamine agonist, took a higher daily levodopa equivalent daily dose, and had more comorbidities. Falls and back pain were more frequent in PD patients with PA than in those without PA. Multiple logistic regression models confirmed an association between PA and male gender, older age, Hoehn and Yahr stage, and total Unified Parkinson's Disease Rating Scale score. CONCLUSIONS: PA are frequent and disabling complications in PD, especially in the advanced disease stages.

Reward sensitivity in Parkinson's patients with binge eating.

BACKGROUND: Parkinson's disease (PD) patients who are treated with dopamine replacement therapy are at risk of developing impulse control disorders (ICDs) (such as gambling, binge eating, and others). According to recent evidence, compulsive reward seeking in ICDs may arise from an excessive attribution of incentive salience (or 'wanting') to rewards. OBJECTIVES: In this study, we tested this hypothesis in patients with PD who developed binge eating (BE). METHODS: Patients with BE, patients without BE, and healthy controls performed different experimental tasks assessing food liking and wanting. Participants first rated the degree of liking and wanting for different foods using explicit self-report measures. They then performed an affective priming task that measured participants' affective reactions towards foods (liking), and a grip-force task that assessed their motivation for food rewards (wanting). All participants also completed several questionnaires assessing impulsivity, reward sensitivity, anxiety and depression, and underwent a neuropsychological evaluation. RESULTS: Patients with BE displayed an altered liking for sweet foods compared to controls but not to patients without BE. Furthermore, this difference emerged only when implicit measures were used. Importantly, an increased wanting was not associated with binge eating even if wanting, but not liking scores significantly correlated with LED levodopa, confirming the hypothesis of a distinction between the two components of rewards. Lastly, binge eating was associated with depression and lower working memory scores. CONCLUSIONS: Take together these results suggest that binge eating in PD is associated with cognitive abnormalities, and to lesser extent affective abnormalities, but not with an increased incentive salience.

Action Observation Plus Sonification. A Novel Therapeutic Protocol for Parkinson's Patient with Freezing of Gait.

Freezing of gait (FoG) is a disabling symptom associated with falls, with little or no responsiveness to pharmacological treatment. Current protocols used for rehabilitation are based on the use of external sensory cues. However, cued strategies might generate an important dependence on the environment. Teaching motor strategies without cues [i.e., action observation (AO) plus Sonification] could represent an alternative/innovative approach to rehabilitation that matters most on appropriate allocation of attention and lightening cognitive load. We aimed to test the effects of a novel experimental protocol to treat patients with Parkinson's disease (PD) and FoG, using functional, and clinical scales. The experimental protocol was based on AO plus Sonification. 12 patients were treated with 8 motor gestures. They watched eight videos showing an actor performing the same eight gestures, and then tried to repeat each gesture. Each video was composed by images and sounds of the gestures. By means of the Sonification technique, the sounds of gestures were obtained by transforming kinematic data (velocity) recorded during gesture execution, into pitch variations. The same 8 motor gestures were also used in a second group of 10 patients; which were treated with a standard protocol based on a common sensory stimulation method. All patients were tested with functional and clinical scales before, after, at 1 month, and 3 months after the treatment. Data showed that the experimental protocol have positive effects on functional and clinical tests. In comparison with the baseline evaluations, significant performance improvements were seen in the NFOG questionnaire, and the UPDRS (parts II and III). Importantly, all these improvements were consistently observed at the end, 1 month, and 3 months after treatment. No improvement effects were found in the group of patients treated with the standard protocol. These data suggest that a multisensory approach based on AO plus Sonification, with the two stimuli semantically related, could help PD patients with FoG to relearn gait movements, to reduce freezing episodes, and that these effects could be prolonged over time.

Treatment of fatigue in multiple sclerosis patients: a neurocognitive approach.

The objective of the study was to treat fatigue in patients with multiple sclerosis (MS) by a neurocognitive rehabilitation program aimed at improving motor planning by using motor imagery (MI). Twenty patients with clinically definite MS complaining of fatigue were treated for five weeks with exercises of neurocognitive rehabilitation twice a week. Patients were evaluated by Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), MSQoL54, Expanded Disability Status Scale (EDSS), and MS Functional Composite (MSFC). After treatment, a decrease in fatigue was detected with both FSS (P = 0.0001) and MFIS (P = 0.0001). MSFC (P = 0.035) and MSQoL54 (P = 0.002) scores improved compared to baseline. At six-month followup, the improvement was confirmed for fatigue (FSS, P = 0.0001; MFIS P = 0.01) and for the physical subscale of MSQoL54 (P = 0.049). No differences in disability scales were found. These results show that neurocognitive rehabilitation, based on MI, could be a strategy to treat fatigue in MS patients.

Acute hemorrhagic leukoencephalitis with atypical features.

Acute hemorrhagic leukoencephalitis (AHL) is a rare demyelinating disease mainly affecting children, characterized by acute onset, progressive course and high mortality. A 62-year-old man was admitted to our Unit for diplopia and ataxia ensuing 2 weeks after the onset of pneumonia. MRI T2-weighted images showed signal hyperintensities in the brainstem. Antibodies against Mycoplasma Pneumoniae and cold agglutinins were found. Two weeks later the patient had a worsening of his conditions: he developed left hemiplegia with motor focal seizures and the day after he was deeply comatose (GCS = 4). A second MRI scan showed extensive hyperintensities involving the whole right hemisphere white matter with a small parietal hemorrhagic area. The clinical and neuroimaging features suggested the diagnosis of AHL, Aciclovir in association with steroid therapy were administered and then plasmapheresis was started. After 30 days of coma, the patient gradually reacquired consciousness and motor functions; anyway a left hemiplegia persisted.