Publications by category
Journal articles
de Natale ER, Wilson H, Politis M (2022). Predictors of RBD progression and conversion to synucleinopathies.
Curr Neurol Neurosci Rep,
22(2), 93-104.
Abstract:
Predictors of RBD progression and conversion to synucleinopathies.
PURPOSE OF REVIEW: Rapid eye movement (REM) sleep behaviour disorder (RBD) is considered the expression of the initial neurodegenerative process underlying synucleinopathies and constitutes the most important marker of their prodromal phase. This article reviews recent research from longitudinal research studies in isolated RBD (iRBD) aiming to describe the most promising progression biomarkers of iRBD and to delineate the current knowledge on the level of prediction of future outcome in iRBD patients at diagnosis. RECENT FINDINGS: Longitudinal studies revealed the potential value of a variety of biomarkers, including clinical markers of motor, autonomic, cognitive, and olfactory symptoms, neurophysiological markers such as REM sleep without atonia and electroencephalography, genetic and epigenetic markers, cerebrospinal fluid and serum markers, and neuroimaging markers to track the progression and predict phenoconversion. To-date the most promising neuroimaging biomarker in iRBD to aid the prediction of phenoconversion is striatal presynaptic striatal dopaminergic dysfunction. There is a variety of potential biomarkers for monitoring disease progression and predicting iRBD conversion into synucleinopathies. A combined multimodal biomarker model could offer a more sensitive and specific tool. Further longitudinal studies are warranted to iRBD as a high-risk population for early neuroprotective interventions and disease-modifying therapies.
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Wilson H, de Natale ER, Politis M (2022). Recent Advances in Neuroimaging Techniques to Assist Clinical Trials on Cell-Based Therapies in Neurodegenerative Diseases.
Stem Cells,
40(8), 724-735.
Abstract:
Recent Advances in Neuroimaging Techniques to Assist Clinical Trials on Cell-Based Therapies in Neurodegenerative Diseases.
Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are progressive disorders for which curative therapy is still lacking. Cell-based therapy aims at replacing dysfunctional cellular populations by repairing damaged tissue and by enriching the microenvironment of selective brain areas, and thus constitutes a promising disease-modifying treatment of neurodegenerative diseases. Scientific research has engineered a wide range of human-derived cellular populations to help overcome some of the logistical, safety, and ethical issues associated with this approach. Open-label studies and clinical trials in human participants have used neuroimaging techniques, such as positron emission tomography (PET) and magnetic resonance imaging (MRI), to assess the success of the transplantation, to evaluate the functional integration of the implanted tissue into the host environment and to understand the pathophysiological changes associated with the therapy. Neuroimaging has constituted an outcome measure of large, randomized clinical trials, and has given answers to clarify the pathophysiology underlying some of the complications linked with this therapy. Novel PET radiotracers and MRI sequences for the staging of neurodegenerative diseases and to study alterations at the molecular level significantly expands the translational potential of neuroimaging to assist pre-clinical and clinical research on cell-based therapy in these disorders. This concise review summarizes the current use of neuroimaging in human studies of cell-based replacement therapy and focuses on the future applications of PET and MRI techniques to evaluate the pathophysiology and treatment efficacy, as well as to aid patient selection and as an outcome measure to improve treatment success.
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Verghese JP, Terry A, de Natale ER, Politis M (2022). Research Evidence of the Role of the Glymphatic System and its Potential Pharmacological Modulation in Neurodegenerative Diseases.
J Clin Med,
11(23).
Abstract:
Research Evidence of the Role of the Glymphatic System and its Potential Pharmacological Modulation in Neurodegenerative Diseases.
The glymphatic system is a unique pathway that utilises end-feet Aquaporin 4 (AQP4) channels within perivascular astrocytes, which is believed to cause cerebrospinal fluid (CSF) inflow into perivascular space (PVS), providing nutrients and waste disposal of the brain parenchyma. It is theorised that the bulk flow of CSF within the PVS removes waste products, soluble proteins, and products of metabolic activity, such as amyloid-β (Aβ). In the experimental model, the glymphatic system is selectively active during slow-wave sleep, and its activity is affected by both sleep dysfunction and deprivation. Dysfunction of the glymphatic system has been proposed as a potential key driver of neurodegeneration. This hypothesis is indirectly supported by the close relationship between neurodegenerative diseases and sleep alterations, frequently occurring years before the clinical diagnosis. Therefore, a detailed characterisation of the function of the glymphatic system in human physiology and disease would shed light on its early stage pathophysiology. The study of the glymphatic system is also critical to identifying means for its pharmacological modulation, which may have the potential for disease modification. This review will critically outline the primary evidence from literature about the dysfunction of the glymphatic system in neurodegeneration and discuss the rationale and current knowledge about pharmacological modulation of the glymphatic system in the animal model and its potential clinical applications in human clinical trials.
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Chandra A, Farrell C, Wilson H, Dervenoulas G, De Natale ER, Politis M (2021). Aquaporin-4 polymorphisms predict amyloid burden and clinical outcome in the Alzheimer's disease spectrum. Neurobiology of Aging, 97, 1-9.
Wilson H, Pagano G, de Natale ER, Mansur A, Caminiti SP, Polychronis S, Middleton LT, Price G, Schmidt KF, Gunn RN, et al (2020). Mitochondrial Complex 1, Sigma 1, and Synaptic Vesicle 2A in Early Drug-Naive Parkinson's Disease.
Mov Disord,
35(8), 1416-1427.
Abstract:
Mitochondrial Complex 1, Sigma 1, and Synaptic Vesicle 2A in Early Drug-Naive Parkinson's Disease.
BACKGROUND: Dysfunction of mitochondrial energy generation may contribute to neurodegeneration, leading to synaptic loss in Parkinson's disease (PD). The objective of this study was to find cross-sectional and longitudinal changes in PET markers of synaptic vesicle protein 2A, sigma 1 receptor, and mitochondrial complex 1 in drug-naive PD patients. METHODS: Twelve early drug-naive PD patients and 16 healthy controls underwent a 3-Tesla MRI and PET imaging to quantify volume of distribution of [11 C]UCB-J, [11 C]SA-4503, and [18 F]BCPP-EF for synaptic vesicle protein 2A, sigma 1 receptor, and mitochondrial complex 1, respectively. Nine PD patients completed approximately 1-year follow-up assessments. RESULTS: Reduced [11 C]UCB-J volume of distribution in the caudate, putamen, thalamus, brain stem, and dorsal raphe and across cortical regions was observed in drug-naive PD patients compared with healthy controls. [11 C]UCB-J volume of distribution was reduced in the locus coeruleus and substantia nigra but did not reach statistical significance. No significant differences were found in [11 C]SA-4503 and [18 F]BCPP-EF volume of distribution in PD compared with healthy controls. Lower brain stem [11 C]UCB-J volume of distribution correlated with Movement Disorder Society Unified Parkinson's Disease Rating Scale part III and total scores. No significant longitudinal changes were identified in PD patients at follow-up compared with baseline. CONCLUSIONS: Our findings represent the first in vivo evidence of mitochondrial, endoplasmic reticulum, and synaptic dysfunction in drug-naive PD patients. Synaptic dysfunction likely occurs early in disease pathophysiology and has relevance to symptomatology. Mitochondrial complex 1 and sigma 1 receptor pathology warrants further investigations in PD. Studies in larger cohorts with longer follow-up will determine the validity of these PET markers to track disease progression. © 2020 the Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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Puligheddu M, Figorilli M, Serra A, Laccu I, Congiu P, Tamburrino L, De Natale ER, Ginatempo F, Deriu F, Loi G, et al (2019). REM Sleep without atonia correlates with abnormal vestibular-evoked myogenic potentials in isolated REM sleep behavior disorder.
Sleep,
42(9).
Abstract:
REM Sleep without atonia correlates with abnormal vestibular-evoked myogenic potentials in isolated REM sleep behavior disorder
The neurophysiological hallmark of REM sleep behavior disorder (RBD) is loss of atonia during REM sleep. Indeed, signs and symptoms of neurodegeneration can occur after years, even decades, from its beginning. This study aimed to measure neurophysiological alterations of the brainstem that potentially correlate with the severity of atonia loss, and determining whether a prodromal neurodegenerative disorder underlines this condition when it occurs as an isolated condition (iRBD). Methods: Subjects with iRBD and matched healthy controls were recruited. The study included the recording of one-night polysomnography, vestibular-evoked myogenic potentials (VEMPs), and a [123I]-FP-CIT dopamine transporter (DAT) scan. The quantification of REM sleep without atonia (RSWA) was made according to two previously published manual methods and one automated method. Results: the rate of alteration of VEMPs and VEMP score were significantly higher in iRBD patients than controls. Moreover, VEMP score was negatively correlated with the automated REM atonia index; a marginal statistical significance was also reached for the positive correlation with the visual tonic electromyographic parameter, while the other correlations, including that with DAT-scan score were not statistically significant. Conclusions: Brainstem neurophysiology in iRBD can be assessed by VEMPs and their alterations may possibly indicate an early expression of the neurodegenerative process underlying this disorder at the brainstem level, which awaits future longitudinal confirmation. The correlation between RSWA and VEMP alteration might also represent a prodromal aspect anticipating the possible evolution from iRBD to neurodegeneration, whereas DAT-scan abnormalities might represent a later step in this evolution.
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De Natale ER, Ginatempo F, Mercante B, Manca A, Magnano I, Ortu E, Pilurzi G, Melis F, Rothwell JC, Deriu F, et al (2019). Vestibulo masseteric reflex and acoustic masseteric Reflex. Normative data and effects of age and gender.
Clinical Neurophysiology,
130(9), 1511-1519.
Abstract:
Vestibulo masseteric reflex and acoustic masseteric Reflex. Normative data and effects of age and gender
Objective: to provide normative data for the Vestibulo-Masseteric Reflex (VMR) and Acoustic-Masseteric Reflex (AMR) in healthy subjects, stratified for age and gender. Methods: a total of 82 healthy subjects (M:F 43:39, mean age 39.3 ± 18.4 years, range 13–79 years) underwent recording of click-evoked VMR and AMR (0.1 ms duration, 5 Hz frequency) from active masseter muscles. Masseter responses to uni- and bilateral stimulation were recorded in a zygomatic and a mandibular configuration, according to the position of the reference electrode. Stimulation intensity curves were recorded for each reflex in ten subjects (mean age 20.7 ± 8.1 years). Gender effect was investigated in 62 subjects and age effect was analyzed in six 10-subject groups aged from 65 years. Onset and peak latencies, interpeak intervals, raw and corrected amplitudes, latency and amplitude asymmetries were analyzed. Results: VMR had a higher elicitation rate than AMR. For both reflexes, rates of elicitation, and corrected amplitudes were higher in the zygomatic configuration, and bilateral stimulation elicited larger responses. Best acoustic ranges of elicitation were 98–113 dB for AMR and 128–138 dB for VMR. Reflex latencies were shorter in females than males. Frequency and amplitude of VMR and AMR decreased substantially over 55 year olds. Conclusions: VMR and AMR can be easily performed in any clinical neurophysiology laboratory. Significance: These reflexes can find application in the investigation of brainstem function in central neurological disorders.
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De Natale ER, Ginatempo F, Laccu I, Figorilli M, Manca A, Mercante B, Puligheddu M, Deriu F (2018). Vestibular evoked myogenic potentials are abnormal in idiopathic REM sleep behavior disorder.
Frontiers in Neurology,
9(OCT).
Abstract:
Vestibular evoked myogenic potentials are abnormal in idiopathic REM sleep behavior disorder
Objectives: to investigate brainstem function in idiopathic REM sleep Behavior Disorder (iRBD), a condition occurring as a result of a derangement of connections within brainstem structures, with a battery of Vestibular Evoked Myogenic Potentials (VEMPs), neurophysiological tools suited for the functional investigation of the brainstem. Neurophysiological data were correlated with clinical characteristics of patients. Methods: Twenty patients with iRBD and 22 healthy controls underwent cervical (cVEMP), masseter (mVEMP) and ocular (oVEMP) VEMP recording. Patients were assessed clinically according to presence of motor as well as non-motor symptoms such as constipation, depression, and hyposmia. Also, they were screened for postural instability through the Berg Balance Scale (BBS). VEMPs were categorized as for increasing degrees of abnormalities, namely latency delay, amplitude reduction and absence; a VEMP score was built accordingly. Results: Compared with controls, iRBD had higher rates of abnormalities both in the VEMP battery (iRBD 75%, Controls 23%; p < 0.01) as well as in each single VEMP (cVEMP: 45 vs. 5%; mVEMP: 65 vs. 13.6%; oVEMP: 50 vs. 5%; p < 0.01), which exhibited significantly lower amplitudes (cVEMP and oVEMP: p < 0.0001; mVEMP: p = 0.001) in iRBD. Within altered reflexes, absence was predominant in oVEMP (81%), amplitude reduction in mVEMP (50%) and cVEMP (70%). Severity of VEMP alterations was significantly higher in iRBD compared with controls (p < 0.05 for all VEMPs), as indicated by the larger VEMP scores in the former. The oVEMP score correlated inversely with poor performances on the BBS. Conclusion: VEMPs unveil consistent and extensive brainstem abnormalities in iRBD patients. Further studies are warranted for testing the potential of VEMPs in the monitoring of the evolution of iRBD over time.
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Cabboi MP, De Natale ER, Devigili G, Lettieri C, Pilurzi G, Eleopra R, Deriu F (2017). 74. Brainstem excitability in Hemifacial Spasm and Post-Facial Palsy Synkinesias and effects of botulinum toxin. Clinical Neurophysiology, 128(12).
De Natale ER, Paulus KS, Aiello E, Sanna B, Manca A, Sotgiu G, Leali PT, Deriu F (2017). Dance therapy improves motor and cognitive functions in patients with Parkinson's disease.
NeuroRehabilitation,
40(1), 141-144.
Abstract:
Dance therapy improves motor and cognitive functions in patients with Parkinson's disease
OBJECTIVE: to explore the effects of Dance Therapy (DT) and Traditional Rehabilitation (TR) on both motor and cognitive domains in Parkinson's Disease patients (PD) with postural instability. METHODS: Sixteen PD patients with recent history of falls were divided in two groups (Dance Therapy, DT and Traditional Rehabilitation, TR); nine patients received 1-hour DT classes twice per week, completing 20 lessons within 10 weeks; seven patients received a similar cycle of 20 group sessions of 60 minutes TR. Motor (Berg Balance Scale - BBS, Gait Dynamic Index - GDI, Timed up and Go Test - TUG, 4 Square-Step Test - 4SST, 6-Minute Walking Test - 6MWT) and cognitive measures (Frontal Assessment Battery - FAB, Trail Making Test a & B - TMT A&B, Stroop Test) were tested at baseline, after the treatment completion and after 8-week follow-up. RESULTS: in the DT group, but not in the TR group, motor and cognitive outcomes significantly improved after treatment and retained after follow-up. Significant changes were found for 6MWT (p=0.028), TUG (p=0.007), TMT-A (p=0.014) and TMT-B (p=0.036). CONCLUSIONS: DT is an unconventional physical therapy for PD patients which effectively impacts on motor (endurance and risk of falls) and non-motor functions (executive functions).
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Manca A, Cabboi MP, Dragone D, Ginatempo F, Ortu E, De Natale ER, Mercante B, Mureddu G, Bua G, Deriu F, et al (2017). Resistance Training for Muscle Weakness in Multiple Sclerosis: Direct Versus Contralateral Approach in Individuals with Ankle Dorsiflexors' Disparity in Strength.
Archives of Physical Medicine and Rehabilitation,
98(7), 1348-1356.e1.
Abstract:
Resistance Training for Muscle Weakness in Multiple Sclerosis: Direct Versus Contralateral Approach in Individuals with Ankle Dorsiflexors' Disparity in Strength
Objective to compare effects of contralateral strength training (CST) and direct strength training of the more affected ankle dorsiflexors on muscle performance and clinical functional outcomes in people with multiple sclerosis (MS) exhibiting interlimb strength asymmetry. Design Randomized controlled trial. Setting University hospital. Participants Individuals with relapsing-remitting MS (N=30) and mild-to-moderate disability (Expanded Disability Status Scale score ≤6) presenting with ankle dorsiflexors' strength disparity. Interventions Participants were randomly assigned to a CST (n=15) or direct strength training (n=15) group performing 6 weeks of maximal intensity strength training of the less or more affected dorsiflexors, respectively. Main Outcome Measures Maximal strength, endurance to fatigue, and mobility outcomes were assessed before, at the intervention end, and at 12-week follow-up. Strength and fatigue parameters were measured after 3 weeks of training (midintervention). Results in the more affected limb of both groups, pre- to postintervention significant increases in maximal strength (P≤.006) and fatigue endurance (P≤.04) were detected along with consistent retention of these improvements at follow-up (P≤.04). At midintervention, the direct strength training group showed significant improvements (P≤.002), with no further increase at postintervention, despite training continuation. Conversely, the CST group showed nonsignificant strength gains, increasing to significance at postintervention (P≤.003). In both groups, significant pre- to postintervention improvements in mobility outcomes (P≤.03), not retained at follow-up, were observed. Conclusions After 6 weeks of training, CST proved as effective as direct strength training in enhancing performance of the more affected limb with a different time course, which may have practical implications in management of severely weakened limbs where direct strength training is not initially possible.
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Manca A, Cabboi MP, Ortu E, Ginatempo F, Dragone D, Zarbo IR, de Natale ER, Mureddu G, Bua G, Deriu F, et al (2016). Effect of contralateral strength training on muscle weakness in people with multiple sclerosis: Proof-of-concept case series.
Physical Therapy,
96(6), 828-838.
Abstract:
Effect of contralateral strength training on muscle weakness in people with multiple sclerosis: Proof-of-concept case series
Background. The contralateral strength training (CST) effect is a transfer of muscle performance to the untrained limb following training of the contralateral side. Objective. The aim of this study was to explore, in individuals with multiple sclerosis (MS) presenting marked lower limb strength asymmetry, the effectiveness of CST on management of muscle weakness of the more-affected limb following training of the less-affected limb. Design. A single-subject research design was used. Methods. Eight individuals with MS underwent 16 to 18 high-intensity training sessions of the less-affected ankle dorsiflexor muscles. The primary outcome measure of this single-system case series was maximal strength expressed as peak moment and maximal work. Secondary outcome measures were: Six-Minute-Walk Test, Timed “Up & Go” Test, 10-Meter Timed Walk Test, and Multiple Sclerosis Quality of Life–54 questionnaire. Results. After the 6-week intervention, the contralateral more affected (untrained) limb showed a 22% to 24% increase in maximal strength. From pretest-posttest measurements, participants also performed significantly better on the clinical and functional secondary outcome measures. At the 12-week follow-up, the strength levels of the weaker untrained limb remained significantly superior to baseline levels in the majority (5 out of 8) of the outcome parameters. Limitations. Considering the design used, the absence of a control group, and the sample size, these findings should be cautiously generalized and will need confirmation in a properly planned randomized controlled trial. Conclusions. The present proof-of-concept study shows, for the first time, the occurrence of the CST effect on muscle performance of ankle dorsiflexor muscles in people with MS. These preliminary findings reveal new potential implications for CST as a promising rehabilitation approach to those conditions where unilateral muscle weakness does not allow or makes difficult performing conventional strength training of the weaker limb.
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de Natale ER, Ginatempo F, Pilurzi G, Ortu E, Mercante B, Manca A, Magnano I, Tolu E, Rothwell JC, Deriu F, et al (2016). ID 267 – Vestibulo-masseteric reflex and acoustic-masseteric reflex: Normative values. Clinical Neurophysiology, 127(3).
Manca A, Ginatempo F, Cabboi MP, Mercante B, Ortu E, Dragone D, De Natale ER, Dvir Z, Rothwell JC, Deriu F, et al (2016). No evidence of neural adaptations following chronic unilateral isometric training of the intrinsic muscles of the hand: a randomized controlled study.
European Journal of Applied Physiology,
116(10), 1993-2005.
Abstract:
No evidence of neural adaptations following chronic unilateral isometric training of the intrinsic muscles of the hand: a randomized controlled study
Purpose: to test whether long-term cortical adaptations occur bilaterally following chronic unilateral training with a simple motor task. Methods: Participants (n = 34) were randomly allocated to a training or control groups. Only the former completed a 4-week maximal-intensity isometric training of the right first dorsal interosseus muscle through key pinching. Maximal strength was assessed bilaterally in four different movements progressively less similar to the training task: key, tip and tripod pinches, and handgrip. Transcranial magnetic stimulation was used to probe, in the left and right primary hand motor cortices, a number of standard tests of cortical excitability, including thresholds, intra-cortical inhibition and facilitation, transcallosal inhibition, and sensory-motor integration. Results: Training increased strength in the trained hand, but only for the tasks specifically involving the trained muscle (key +8.5 %; p
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de Natale ER, Ginatempo F, Manca A, Paulus KS, Agnetti V, Tolu E, Deriu F (2016). Paired neurophysiological and clinical approach to brainstem assessment in Parkinson’s Disease. Clinical Neurophysiology, 127(3).
Deriu F, de Natale ER, Magnano I, Ginatempo F (2016). VEMPs in central neurological disorders. Clinical Neurophysiology, 127(4), 2020-2021.
Manca A, Pisanu F, Ortu E, De Natale ER, Ginatempo F, Dragone D, Tolu E, Deriu F (2015). A comprehensive assessment of the cross-training effect in ankle dorsiflexors of healthy subjects: a randomized controlled study.
Gait and Posture,
42(1), 1-6.
Abstract:
A comprehensive assessment of the cross-training effect in ankle dorsiflexors of healthy subjects: a randomized controlled study
Purpose: to investigate the cross-training effect, induced on ankle dorsiflexors (AD) by unilateral strength-training of the contralateral muscles, as transfer of peak torque (PT) and muscle work (MW) and their relative contributions to muscle performance. Methods: Thirty healthy volunteers were randomly assigned to a training or control group. The trained group sustained a 4-week maximal isokinetic training of the stronger AD at 90 and 45°/s. At both angular velocities, PT, MW and MW/PT ratio were measured from both legs at baseline and after intervention (trained group) or no-intervention (controls). The familiarization/learning-effect was calculated and subtracted by PT and MW measures to obtain their net changes. Results: Net PT increased in both legs (untrained: +27.5% at 90°/s and +17.9% at 45°/s; trained: +15% at 90°/s and +16.3% at 45°/s). Similarly, net MW increased in both the untrained (90°/s: +29.6%; 45°/s: +37%) and trained (90°/s: +23.4%; 45°/s: +18.3%) legs. PT and MW gains were larger in the untrained than trained AD (p< 0.0005), with MW improving more than PT at 45°/s (p= 0.04). The MW/PT ratio increased bilaterally only in the trained group (p< 0.05), depending on the angular velocity. Conclusions: the cross-training effect occurred in AD muscles in terms of both PT and MW, with MW adding valuable information to PT-analysis in describing muscle performance. Moreover, the MW/PT ratio allowed estimating the contributions of these parameters to muscle capability and may represent a novel index in isokinetic testing. The greater improvements in the untrained than trained limb raises interesting clinical implications in asymmetric conditions.
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de Natale ER, Ginatempo F, Paulus KS, Pes GM, Manca A, Tolu E, Agnetti V, Deriu F (2015). Abnormalities of vestibular-evoked myogenic potentials in idiopathic Parkinson’s disease are associated with clinical evidence of brainstem involvement.
Neurological Sciences,
36(6), 995-1001.
Abstract:
Abnormalities of vestibular-evoked myogenic potentials in idiopathic Parkinson’s disease are associated with clinical evidence of brainstem involvement
Brainstem degeneration in Parkinson’s disease (PD) may explain the occurrence of many non-motor symptoms in this condition. Purposes of the present work were to investigate brainstem function in PD through a battery of vestibular-evoked myogenic potentials (VEMP) allowing a comprehensive brainstem exploration and to correlate VEMP findings with symptoms related to brainstem involvement. Cervical (cVEMP), masseter (mVEMP) and ocular (oVEMP) VEMPs were investigated in 24 PD patients and compared with those recorded in 24 age-matched controls. Presence of symptoms ascribable to brainstem dysfunction, such as daytime sleepiness, REM sleep behavior disorder and depression, was investigated through Epworth Sleepiness Scale, Parkinson’s Disease Sleep Scale, REM Sleep Disorder Screening Questionnaire (RBD-SQ) and Geriatric Depression Scale. Postural instability was additionally assessed through mini-BESTest. The frequency of alteration of VEMPs in patients was 83.3 % when considering the whole set and 41.7 % for cVEMP, 66.7 % for mVEMP and 45.8 % for oVEMP. This was significantly different from controls, with absence being the prevalent alteration in PD. A significant inverse correlation between the number of altered VEMPs and mini-BESTest and a direct correlation with RBD-SQ were found. The VEMP battery under study allowed the identification of brainstem dysfunctions in PD patients, which correlated with clinical tests suggestive of postural and REM sleep disorders. VEMPs might represent a valuable tool of brainstem assessment in PD.
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Manca A, Pisanu F, Ortu E, De Natale E, Ginatempo F, Dragone D, Leali PT, Deriu F (2015). Isokinetic cross-training effect in foot drop following common peroneal nerve injury.
Isokinetics and Exercise Science,
23(1), 17-20.
Abstract:
Isokinetic cross-training effect in foot drop following common peroneal nerve injury
Background: to our knowledge, no studies on foot drop (FD) caused by peripheral nerve lesion have investigated whether unilateral training of the unaffected ankle dorsiflexors induced a clinically meaningful strength improvement in the affected-untrained leg, namely a cross-training (CT) effect. METHOD: a 59-year-old man, who suffered since childhood from surgically-induced damage of the common peroneal nerve, performed an 8-week maximal-intensity isokinetic training of the healthy leg. Before and after training, patient underwent: bilateral isokinetic testing; functional and mobility tests including 6-minute walking test, 10-meter walking test, timed-up-and-go test and ankle ROM; neurophysiological recordings including motor thresholds, cortical silent period of the hemisphere innervating the affected tibialis anterior and mean EMG recruitment. Results: After cross-training, the affected-untrained dorsiflexors showed notable increases in all dynamometric parameters. Similarly, all functional tests improved considerably. The cortical silent period was reduced and the maximal EMG recruitment increased. Conclusions: Improvements in muscle performance and neurophysiological drive in the affected non-trained limb due to training of the unaffected side indicate that cross-training may be a viable rehabilitative approach to foot drop.
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de Natale ER, Ginatempo F, Paulus KS, Manca A, Mercante B, Pes GM, Agnetti V, Tolu E, Deriu F (2015). Paired neurophysiological and clinical study of the brainstem at different stages of Parkinson's Disease.
Clinical Neurophysiology,
126(10), 1871-1878.
Abstract:
Paired neurophysiological and clinical study of the brainstem at different stages of Parkinson's Disease
Objective: to study brainstem function in Parkinson's Disease (PD) at different stages, through a battery of vestibular-evoked myogenic potentials (VEMPs) and compare the results with scores on clinical scales assessing the presence of symptoms linked to brainstem involvement. Methods: Cervical, masseter and ocular VEMPs were recorded in patients with early PD (n= 14, disease duration 1.42 ± 0.7. years), advanced PD (n= 19, disease duration 7.26 ± 2.9. years) and in 27 age-matched controls. In PD, the following clinical scales were administered: Mini-BESTest, REM sleep Behavior Disorder Screening Questionnaire (RBD-SQ), PD Sleep Scale, Epworth Sleepiness Scale and Geriatric Depression Scale. Results: Rate of VEMPs alterations was higher (p
Abstract.
Manca A, Ortu E, Ginatempo F, De Natale ER, Pisanu F, Deriu F (2014). P243: Rehabilitation of drop-foot with maximal isokinetic cross-training: a case report. Clinical Neurophysiology, 125
Manca A, Limonta E, Pilurzi G, Ginatempo F, De Natale ER, Mercante B, Tolu E, Deriu F (2014). Ultrasound and Laser as Stand-Alone Therapies for Myofascial Trigger Points: a Randomized, Double-Blind, Placebo-Controlled Study.
Physiotherapy Research International,
19(3), 166-175.
Abstract:
Ultrasound and Laser as Stand-Alone Therapies for Myofascial Trigger Points: a Randomized, Double-Blind, Placebo-Controlled Study
Background and Purpose: Ultrasound (US) and low-level laser therapy (LLLT) are commonly employed for myofascial trigger points (MTP) despite lack of evidence for usage as stand-alone treatments. The aim of the study was to determine, on MTP of the upper trapezius muscle (uTM), the effects of US and LLLT per se, as delivered in accordance with the procedures reported by surveys about their usage among physiotherapists. Methods: Design was set as a double-blind, randomized, placebo-controlled study. Sixty participants with at least one active MTP in uTM (28 women and 32 men; mean age 24.5±1.44years) were recruited and randomly assigned to one out of five groups: active US (n=12), placebo US (n=12), active LLLT (n=11), placebo LLLT (n=11) and no therapy (control, n=14). The participants and outcome assessor were blinded to the group assignment and therapy delivered. Three outcome measures were assessed at baseline, after a 2-week treatment and 12weeks after the end of the intervention (follow-up): pressure pain threshold, subjective pain on a numerical rating scale and muscle extensibility performing a cervical lateral flexion. All subjects assigned to the intervention groups were treated five times weekly for overall 10 treatments given. Two-way ANOVA was used to compare differences before and after intervention and among groups at each time-point. Results: After the 2-week intervention, all groups showed pressure pain threshold, numerical rating scale and cervical lateral flexion significant improvements (p
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Paulus KS, Meloni M, Carpentras G, Sassu C, De Natale E, Deriu F, Galistu P, Agnetti V (2012). 4 Parkinson’s disease and conversion disorder: Case report and literature review. Basal Ganglia, 2(4).
Chapters
de Natale ER, Wilson H, Politis M (2023). Chapter 1 Parkinson's disease and related disorders the pursuit for reliable readouts and the role of neuroimaging. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 3-19.
Tondo G, Comi C, Naldi A, de Natale ER, Politis M (2023). Chapter 12 Neuroimaging in multiple system atrophy. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 311-354.
de Natale ER, Wilson H, Politis M, Niccolini F (2023). Chapter 13 Neuroimaging in progressive supranuclear palsy. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 355-397.
Wilson H, de Natale ER, Politis M, Niccolini F (2023). Chapter 14 Neuroimaging in corticobasal syndrome. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 399-417.
de Natale ER, Wilson H, Niccolini F, Politis M (2023). Chapter 15 Molecular imaging in Huntington's disease. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 421-448.
Belogianni C, Wilson H, de Natale ER, Politis M (2023). Chapter 16 Magnetic resonance imaging in Huntington's disease. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 449-489.
Terry A, de Natale ER, Politis M (2023). Chapter 17 Neuroimaging in essential tremor. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 491-518.
de Natale ER, Wilson H, Udeh-Momoh C, Ford JK, Politis M, Middleton LT (2023). Chapter 18 How molecular imaging studies can disentangle disease mechanisms in age-related neurodegenerative disorders. In (Ed) Aging, 455-492.
de Natale ER, Wilson H, Politis M (2023). Chapter 18 Neuroimaging of restless legs syndrome. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 519-540.
Wilson H, de Natale ER, Politis M (2023). Chapter 2 Advances in magnetic resonance imaging. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 21-52.
de Natale ER, Wilson H, Politis M (2023). Chapter 4 Dopaminergic molecular imaging in familial and idiopathic Parkinson's disease. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 69-104.
Verghese JP, de Natale ER, Politis M (2023). Chapter 7 Structural MRI in familial and idiopathic PD. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 151-199.
Verghese JP, de Natale ER, Politis M (2023). Chapter 8 Functional MRI in familial and idiopathic PD. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 201-250.
de Natale ER, Verghese JP, Wilson H, Politis M (2023). Chapter 9 Molecular imaging in prodromal Parkinson’s disease. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 251-272.
De Natale ER, Wilson H, Politis M (2022). Imaging Biomarkers in Huntington’s Disease. In (Ed)
Neuromethods, 457-505.
Abstract:
Imaging Biomarkers in Huntington’s Disease
Abstract.
De Natale ER, Wilson H, Politis M (2021). Imaging BiomarkersBiomarkers in Huntington’s DiseaseHuntington’s disease (HD). In (Ed) Neurodegenerative Diseases Biomarkers, 457-505.
Wilson H, de Natale ER, Politis M (2021). Nucleus basalis of Meynert degeneration predicts cognitive impairment in Parkinson's disease. In (Ed)
Handbook of Clinical Neurology, 189-205.
Abstract:
Nucleus basalis of Meynert degeneration predicts cognitive impairment in Parkinson's disease
Abstract.
de Natale ER, Wilson H, Politis M (2021). Serotonergic imaging in Parkinson's disease. In (Ed)
Progress in Brain Research, 303-338.
Abstract:
Serotonergic imaging in Parkinson's disease
Abstract.
de Natale ER, Wilson H, Pagano G, Politis M (2018). Imaging Transplantation in Movement Disorders. In (Ed)
IMAGING IN MOVEMENT DISORDERS: IMAGING APPLICATIONS IN NON-PARKINSONIAN AND OTHER MOVEMENT DISORDERS, 213-263.
Author URL.
de Natale ER, Niccolini F, Wilson H, Politis M (2018). Molecular Imaging of the Dopaminergic System in Idiopathic Parkinson's Disease. In (Ed)
IMAGING IN MOVEMENT DISORDERS: IMAGING METHODOLOGY AND APPLICATIONS IN PARKINSON'S DISEASE, 131-172.
Author URL.
Conferences
de Natale E, Wilson H, Politis M (2020). Structural and microstructural pathology in early de novo Parkinson's disease patients with depression: an MRI study.
Author URL.
Puligheddu M, Figorilli M, Serra A, Laccu I, Congiu P, Tamburrino L, de Natale ER, Ginatempo F, Deriu F, Loi G, et al (2019). ABNORMAL VESTIBULAR EVOKED MYOGENIC POTENTIALS ARE CORRELATED WITH REM SLEEP WITHOUT ATONIA IN PATIENTS WITH ISOLATED REM SLEEP BEHAVIOR DISORDER.
Author URL.
Puligheddu M, Figorilli M, Laccu I, Congiu P, Gioi G, Tamburrino L, de Natale ER, Ginatempo F, Deriu F, Fantini ML, et al (2017). SEVERITY OF REM SLEEP MUSCLE ATONIA LOSS IN IDIOPATHIC REM SLEEP BEHAVIOUR DISORDER CORRELATES WITH THE DEGREE OF ABNORMALITIES IN THE VESTIBULAR EVOKED MYOGENIC POTENTIALS.
Author URL.
Publications by year
2023
de Natale ER, Wilson H, Politis M (2023). Chapter 1 Parkinson's disease and related disorders the pursuit for reliable readouts and the role of neuroimaging. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 3-19.
Tondo G, Comi C, Naldi A, de Natale ER, Politis M (2023). Chapter 12 Neuroimaging in multiple system atrophy. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 311-354.
de Natale ER, Wilson H, Politis M, Niccolini F (2023). Chapter 13 Neuroimaging in progressive supranuclear palsy. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 355-397.
Wilson H, de Natale ER, Politis M, Niccolini F (2023). Chapter 14 Neuroimaging in corticobasal syndrome. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 399-417.
de Natale ER, Wilson H, Niccolini F, Politis M (2023). Chapter 15 Molecular imaging in Huntington's disease. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 421-448.
Belogianni C, Wilson H, de Natale ER, Politis M (2023). Chapter 16 Magnetic resonance imaging in Huntington's disease. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 449-489.
Terry A, de Natale ER, Politis M (2023). Chapter 17 Neuroimaging in essential tremor. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 491-518.
de Natale ER, Wilson H, Udeh-Momoh C, Ford JK, Politis M, Middleton LT (2023). Chapter 18 How molecular imaging studies can disentangle disease mechanisms in age-related neurodegenerative disorders. In (Ed) Aging, 455-492.
de Natale ER, Wilson H, Politis M (2023). Chapter 18 Neuroimaging of restless legs syndrome. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 519-540.
Wilson H, de Natale ER, Politis M (2023). Chapter 2 Advances in magnetic resonance imaging. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 21-52.
de Natale ER, Wilson H, Politis M (2023). Chapter 4 Dopaminergic molecular imaging in familial and idiopathic Parkinson's disease. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 69-104.
Verghese JP, de Natale ER, Politis M (2023). Chapter 7 Structural MRI in familial and idiopathic PD. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 151-199.
Verghese JP, de Natale ER, Politis M (2023). Chapter 8 Functional MRI in familial and idiopathic PD. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 201-250.
de Natale ER, Verghese JP, Wilson H, Politis M (2023). Chapter 9 Molecular imaging in prodromal Parkinson’s disease. In (Ed) Neuroimaging in Parkinson�s Disease and Related Disorders, 251-272.
2022
De Natale ER, Wilson H, Politis M (2022). Imaging Biomarkers in Huntington’s Disease. In (Ed)
Neuromethods, 457-505.
Abstract:
Imaging Biomarkers in Huntington’s Disease
Abstract.
de Natale ER, Wilson H, Politis M (2022). Predictors of RBD progression and conversion to synucleinopathies.
Curr Neurol Neurosci Rep,
22(2), 93-104.
Abstract:
Predictors of RBD progression and conversion to synucleinopathies.
PURPOSE OF REVIEW: Rapid eye movement (REM) sleep behaviour disorder (RBD) is considered the expression of the initial neurodegenerative process underlying synucleinopathies and constitutes the most important marker of their prodromal phase. This article reviews recent research from longitudinal research studies in isolated RBD (iRBD) aiming to describe the most promising progression biomarkers of iRBD and to delineate the current knowledge on the level of prediction of future outcome in iRBD patients at diagnosis. RECENT FINDINGS: Longitudinal studies revealed the potential value of a variety of biomarkers, including clinical markers of motor, autonomic, cognitive, and olfactory symptoms, neurophysiological markers such as REM sleep without atonia and electroencephalography, genetic and epigenetic markers, cerebrospinal fluid and serum markers, and neuroimaging markers to track the progression and predict phenoconversion. To-date the most promising neuroimaging biomarker in iRBD to aid the prediction of phenoconversion is striatal presynaptic striatal dopaminergic dysfunction. There is a variety of potential biomarkers for monitoring disease progression and predicting iRBD conversion into synucleinopathies. A combined multimodal biomarker model could offer a more sensitive and specific tool. Further longitudinal studies are warranted to iRBD as a high-risk population for early neuroprotective interventions and disease-modifying therapies.
Abstract.
Author URL.
Wilson H, de Natale ER, Politis M (2022). Recent Advances in Neuroimaging Techniques to Assist Clinical Trials on Cell-Based Therapies in Neurodegenerative Diseases.
Stem Cells,
40(8), 724-735.
Abstract:
Recent Advances in Neuroimaging Techniques to Assist Clinical Trials on Cell-Based Therapies in Neurodegenerative Diseases.
Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are progressive disorders for which curative therapy is still lacking. Cell-based therapy aims at replacing dysfunctional cellular populations by repairing damaged tissue and by enriching the microenvironment of selective brain areas, and thus constitutes a promising disease-modifying treatment of neurodegenerative diseases. Scientific research has engineered a wide range of human-derived cellular populations to help overcome some of the logistical, safety, and ethical issues associated with this approach. Open-label studies and clinical trials in human participants have used neuroimaging techniques, such as positron emission tomography (PET) and magnetic resonance imaging (MRI), to assess the success of the transplantation, to evaluate the functional integration of the implanted tissue into the host environment and to understand the pathophysiological changes associated with the therapy. Neuroimaging has constituted an outcome measure of large, randomized clinical trials, and has given answers to clarify the pathophysiology underlying some of the complications linked with this therapy. Novel PET radiotracers and MRI sequences for the staging of neurodegenerative diseases and to study alterations at the molecular level significantly expands the translational potential of neuroimaging to assist pre-clinical and clinical research on cell-based therapy in these disorders. This concise review summarizes the current use of neuroimaging in human studies of cell-based replacement therapy and focuses on the future applications of PET and MRI techniques to evaluate the pathophysiology and treatment efficacy, as well as to aid patient selection and as an outcome measure to improve treatment success.
Abstract.
Author URL.
Verghese JP, Terry A, de Natale ER, Politis M (2022). Research Evidence of the Role of the Glymphatic System and its Potential Pharmacological Modulation in Neurodegenerative Diseases.
J Clin Med,
11(23).
Abstract:
Research Evidence of the Role of the Glymphatic System and its Potential Pharmacological Modulation in Neurodegenerative Diseases.
The glymphatic system is a unique pathway that utilises end-feet Aquaporin 4 (AQP4) channels within perivascular astrocytes, which is believed to cause cerebrospinal fluid (CSF) inflow into perivascular space (PVS), providing nutrients and waste disposal of the brain parenchyma. It is theorised that the bulk flow of CSF within the PVS removes waste products, soluble proteins, and products of metabolic activity, such as amyloid-β (Aβ). In the experimental model, the glymphatic system is selectively active during slow-wave sleep, and its activity is affected by both sleep dysfunction and deprivation. Dysfunction of the glymphatic system has been proposed as a potential key driver of neurodegeneration. This hypothesis is indirectly supported by the close relationship between neurodegenerative diseases and sleep alterations, frequently occurring years before the clinical diagnosis. Therefore, a detailed characterisation of the function of the glymphatic system in human physiology and disease would shed light on its early stage pathophysiology. The study of the glymphatic system is also critical to identifying means for its pharmacological modulation, which may have the potential for disease modification. This review will critically outline the primary evidence from literature about the dysfunction of the glymphatic system in neurodegeneration and discuss the rationale and current knowledge about pharmacological modulation of the glymphatic system in the animal model and its potential clinical applications in human clinical trials.
Abstract.
Author URL.
2021
Chandra A, Farrell C, Wilson H, Dervenoulas G, De Natale ER, Politis M (2021). Aquaporin-4 polymorphisms predict amyloid burden and clinical outcome in the Alzheimer's disease spectrum. Neurobiology of Aging, 97, 1-9.
De Natale ER, Wilson H, Politis M (2021). Imaging BiomarkersBiomarkers in Huntington’s DiseaseHuntington’s disease (HD). In (Ed) Neurodegenerative Diseases Biomarkers, 457-505.
Wilson H, de Natale ER, Politis M (2021). Nucleus basalis of Meynert degeneration predicts cognitive impairment in Parkinson's disease. In (Ed)
Handbook of Clinical Neurology, 189-205.
Abstract:
Nucleus basalis of Meynert degeneration predicts cognitive impairment in Parkinson's disease
Abstract.
de Natale ER, Wilson H, Politis M (2021). Serotonergic imaging in Parkinson's disease. In (Ed)
Progress in Brain Research, 303-338.
Abstract:
Serotonergic imaging in Parkinson's disease
Abstract.
2020
Wilson H, Pagano G, de Natale ER, Mansur A, Caminiti SP, Polychronis S, Middleton LT, Price G, Schmidt KF, Gunn RN, et al (2020). Mitochondrial Complex 1, Sigma 1, and Synaptic Vesicle 2A in Early Drug-Naive Parkinson's Disease.
Mov Disord,
35(8), 1416-1427.
Abstract:
Mitochondrial Complex 1, Sigma 1, and Synaptic Vesicle 2A in Early Drug-Naive Parkinson's Disease.
BACKGROUND: Dysfunction of mitochondrial energy generation may contribute to neurodegeneration, leading to synaptic loss in Parkinson's disease (PD). The objective of this study was to find cross-sectional and longitudinal changes in PET markers of synaptic vesicle protein 2A, sigma 1 receptor, and mitochondrial complex 1 in drug-naive PD patients. METHODS: Twelve early drug-naive PD patients and 16 healthy controls underwent a 3-Tesla MRI and PET imaging to quantify volume of distribution of [11 C]UCB-J, [11 C]SA-4503, and [18 F]BCPP-EF for synaptic vesicle protein 2A, sigma 1 receptor, and mitochondrial complex 1, respectively. Nine PD patients completed approximately 1-year follow-up assessments. RESULTS: Reduced [11 C]UCB-J volume of distribution in the caudate, putamen, thalamus, brain stem, and dorsal raphe and across cortical regions was observed in drug-naive PD patients compared with healthy controls. [11 C]UCB-J volume of distribution was reduced in the locus coeruleus and substantia nigra but did not reach statistical significance. No significant differences were found in [11 C]SA-4503 and [18 F]BCPP-EF volume of distribution in PD compared with healthy controls. Lower brain stem [11 C]UCB-J volume of distribution correlated with Movement Disorder Society Unified Parkinson's Disease Rating Scale part III and total scores. No significant longitudinal changes were identified in PD patients at follow-up compared with baseline. CONCLUSIONS: Our findings represent the first in vivo evidence of mitochondrial, endoplasmic reticulum, and synaptic dysfunction in drug-naive PD patients. Synaptic dysfunction likely occurs early in disease pathophysiology and has relevance to symptomatology. Mitochondrial complex 1 and sigma 1 receptor pathology warrants further investigations in PD. Studies in larger cohorts with longer follow-up will determine the validity of these PET markers to track disease progression. © 2020 the Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Abstract.
Author URL.
de Natale E, Wilson H, Politis M (2020). Structural and microstructural pathology in early de novo Parkinson's disease patients with depression: an MRI study.
Author URL.
2019
Puligheddu M, Figorilli M, Serra A, Laccu I, Congiu P, Tamburrino L, de Natale ER, Ginatempo F, Deriu F, Loi G, et al (2019). ABNORMAL VESTIBULAR EVOKED MYOGENIC POTENTIALS ARE CORRELATED WITH REM SLEEP WITHOUT ATONIA IN PATIENTS WITH ISOLATED REM SLEEP BEHAVIOR DISORDER.
Author URL.
Puligheddu M, Figorilli M, Serra A, Laccu I, Congiu P, Tamburrino L, De Natale ER, Ginatempo F, Deriu F, Loi G, et al (2019). REM Sleep without atonia correlates with abnormal vestibular-evoked myogenic potentials in isolated REM sleep behavior disorder.
Sleep,
42(9).
Abstract:
REM Sleep without atonia correlates with abnormal vestibular-evoked myogenic potentials in isolated REM sleep behavior disorder
The neurophysiological hallmark of REM sleep behavior disorder (RBD) is loss of atonia during REM sleep. Indeed, signs and symptoms of neurodegeneration can occur after years, even decades, from its beginning. This study aimed to measure neurophysiological alterations of the brainstem that potentially correlate with the severity of atonia loss, and determining whether a prodromal neurodegenerative disorder underlines this condition when it occurs as an isolated condition (iRBD). Methods: Subjects with iRBD and matched healthy controls were recruited. The study included the recording of one-night polysomnography, vestibular-evoked myogenic potentials (VEMPs), and a [123I]-FP-CIT dopamine transporter (DAT) scan. The quantification of REM sleep without atonia (RSWA) was made according to two previously published manual methods and one automated method. Results: the rate of alteration of VEMPs and VEMP score were significantly higher in iRBD patients than controls. Moreover, VEMP score was negatively correlated with the automated REM atonia index; a marginal statistical significance was also reached for the positive correlation with the visual tonic electromyographic parameter, while the other correlations, including that with DAT-scan score were not statistically significant. Conclusions: Brainstem neurophysiology in iRBD can be assessed by VEMPs and their alterations may possibly indicate an early expression of the neurodegenerative process underlying this disorder at the brainstem level, which awaits future longitudinal confirmation. The correlation between RSWA and VEMP alteration might also represent a prodromal aspect anticipating the possible evolution from iRBD to neurodegeneration, whereas DAT-scan abnormalities might represent a later step in this evolution.
Abstract.
De Natale ER, Ginatempo F, Mercante B, Manca A, Magnano I, Ortu E, Pilurzi G, Melis F, Rothwell JC, Deriu F, et al (2019). Vestibulo masseteric reflex and acoustic masseteric Reflex. Normative data and effects of age and gender.
Clinical Neurophysiology,
130(9), 1511-1519.
Abstract:
Vestibulo masseteric reflex and acoustic masseteric Reflex. Normative data and effects of age and gender
Objective: to provide normative data for the Vestibulo-Masseteric Reflex (VMR) and Acoustic-Masseteric Reflex (AMR) in healthy subjects, stratified for age and gender. Methods: a total of 82 healthy subjects (M:F 43:39, mean age 39.3 ± 18.4 years, range 13–79 years) underwent recording of click-evoked VMR and AMR (0.1 ms duration, 5 Hz frequency) from active masseter muscles. Masseter responses to uni- and bilateral stimulation were recorded in a zygomatic and a mandibular configuration, according to the position of the reference electrode. Stimulation intensity curves were recorded for each reflex in ten subjects (mean age 20.7 ± 8.1 years). Gender effect was investigated in 62 subjects and age effect was analyzed in six 10-subject groups aged from 65 years. Onset and peak latencies, interpeak intervals, raw and corrected amplitudes, latency and amplitude asymmetries were analyzed. Results: VMR had a higher elicitation rate than AMR. For both reflexes, rates of elicitation, and corrected amplitudes were higher in the zygomatic configuration, and bilateral stimulation elicited larger responses. Best acoustic ranges of elicitation were 98–113 dB for AMR and 128–138 dB for VMR. Reflex latencies were shorter in females than males. Frequency and amplitude of VMR and AMR decreased substantially over 55 year olds. Conclusions: VMR and AMR can be easily performed in any clinical neurophysiology laboratory. Significance: These reflexes can find application in the investigation of brainstem function in central neurological disorders.
Abstract.
2018
de Natale ER, Wilson H, Pagano G, Politis M (2018). Imaging Transplantation in Movement Disorders. In (Ed)
IMAGING IN MOVEMENT DISORDERS: IMAGING APPLICATIONS IN NON-PARKINSONIAN AND OTHER MOVEMENT DISORDERS, 213-263.
Author URL.
de Natale ER, Niccolini F, Wilson H, Politis M (2018). Molecular Imaging of the Dopaminergic System in Idiopathic Parkinson's Disease. In (Ed)
IMAGING IN MOVEMENT DISORDERS: IMAGING METHODOLOGY AND APPLICATIONS IN PARKINSON'S DISEASE, 131-172.
Author URL.
De Natale ER, Ginatempo F, Laccu I, Figorilli M, Manca A, Mercante B, Puligheddu M, Deriu F (2018). Vestibular evoked myogenic potentials are abnormal in idiopathic REM sleep behavior disorder.
Frontiers in Neurology,
9(OCT).
Abstract:
Vestibular evoked myogenic potentials are abnormal in idiopathic REM sleep behavior disorder
Objectives: to investigate brainstem function in idiopathic REM sleep Behavior Disorder (iRBD), a condition occurring as a result of a derangement of connections within brainstem structures, with a battery of Vestibular Evoked Myogenic Potentials (VEMPs), neurophysiological tools suited for the functional investigation of the brainstem. Neurophysiological data were correlated with clinical characteristics of patients. Methods: Twenty patients with iRBD and 22 healthy controls underwent cervical (cVEMP), masseter (mVEMP) and ocular (oVEMP) VEMP recording. Patients were assessed clinically according to presence of motor as well as non-motor symptoms such as constipation, depression, and hyposmia. Also, they were screened for postural instability through the Berg Balance Scale (BBS). VEMPs were categorized as for increasing degrees of abnormalities, namely latency delay, amplitude reduction and absence; a VEMP score was built accordingly. Results: Compared with controls, iRBD had higher rates of abnormalities both in the VEMP battery (iRBD 75%, Controls 23%; p < 0.01) as well as in each single VEMP (cVEMP: 45 vs. 5%; mVEMP: 65 vs. 13.6%; oVEMP: 50 vs. 5%; p < 0.01), which exhibited significantly lower amplitudes (cVEMP and oVEMP: p < 0.0001; mVEMP: p = 0.001) in iRBD. Within altered reflexes, absence was predominant in oVEMP (81%), amplitude reduction in mVEMP (50%) and cVEMP (70%). Severity of VEMP alterations was significantly higher in iRBD compared with controls (p < 0.05 for all VEMPs), as indicated by the larger VEMP scores in the former. The oVEMP score correlated inversely with poor performances on the BBS. Conclusion: VEMPs unveil consistent and extensive brainstem abnormalities in iRBD patients. Further studies are warranted for testing the potential of VEMPs in the monitoring of the evolution of iRBD over time.
Abstract.
2017
Cabboi MP, De Natale ER, Devigili G, Lettieri C, Pilurzi G, Eleopra R, Deriu F (2017). 74. Brainstem excitability in Hemifacial Spasm and Post-Facial Palsy Synkinesias and effects of botulinum toxin. Clinical Neurophysiology, 128(12).
De Natale ER, Paulus KS, Aiello E, Sanna B, Manca A, Sotgiu G, Leali PT, Deriu F (2017). Dance therapy improves motor and cognitive functions in patients with Parkinson's disease.
NeuroRehabilitation,
40(1), 141-144.
Abstract:
Dance therapy improves motor and cognitive functions in patients with Parkinson's disease
OBJECTIVE: to explore the effects of Dance Therapy (DT) and Traditional Rehabilitation (TR) on both motor and cognitive domains in Parkinson's Disease patients (PD) with postural instability. METHODS: Sixteen PD patients with recent history of falls were divided in two groups (Dance Therapy, DT and Traditional Rehabilitation, TR); nine patients received 1-hour DT classes twice per week, completing 20 lessons within 10 weeks; seven patients received a similar cycle of 20 group sessions of 60 minutes TR. Motor (Berg Balance Scale - BBS, Gait Dynamic Index - GDI, Timed up and Go Test - TUG, 4 Square-Step Test - 4SST, 6-Minute Walking Test - 6MWT) and cognitive measures (Frontal Assessment Battery - FAB, Trail Making Test a & B - TMT A&B, Stroop Test) were tested at baseline, after the treatment completion and after 8-week follow-up. RESULTS: in the DT group, but not in the TR group, motor and cognitive outcomes significantly improved after treatment and retained after follow-up. Significant changes were found for 6MWT (p=0.028), TUG (p=0.007), TMT-A (p=0.014) and TMT-B (p=0.036). CONCLUSIONS: DT is an unconventional physical therapy for PD patients which effectively impacts on motor (endurance and risk of falls) and non-motor functions (executive functions).
Abstract.
Manca A, Cabboi MP, Dragone D, Ginatempo F, Ortu E, De Natale ER, Mercante B, Mureddu G, Bua G, Deriu F, et al (2017). Resistance Training for Muscle Weakness in Multiple Sclerosis: Direct Versus Contralateral Approach in Individuals with Ankle Dorsiflexors' Disparity in Strength.
Archives of Physical Medicine and Rehabilitation,
98(7), 1348-1356.e1.
Abstract:
Resistance Training for Muscle Weakness in Multiple Sclerosis: Direct Versus Contralateral Approach in Individuals with Ankle Dorsiflexors' Disparity in Strength
Objective to compare effects of contralateral strength training (CST) and direct strength training of the more affected ankle dorsiflexors on muscle performance and clinical functional outcomes in people with multiple sclerosis (MS) exhibiting interlimb strength asymmetry. Design Randomized controlled trial. Setting University hospital. Participants Individuals with relapsing-remitting MS (N=30) and mild-to-moderate disability (Expanded Disability Status Scale score ≤6) presenting with ankle dorsiflexors' strength disparity. Interventions Participants were randomly assigned to a CST (n=15) or direct strength training (n=15) group performing 6 weeks of maximal intensity strength training of the less or more affected dorsiflexors, respectively. Main Outcome Measures Maximal strength, endurance to fatigue, and mobility outcomes were assessed before, at the intervention end, and at 12-week follow-up. Strength and fatigue parameters were measured after 3 weeks of training (midintervention). Results in the more affected limb of both groups, pre- to postintervention significant increases in maximal strength (P≤.006) and fatigue endurance (P≤.04) were detected along with consistent retention of these improvements at follow-up (P≤.04). At midintervention, the direct strength training group showed significant improvements (P≤.002), with no further increase at postintervention, despite training continuation. Conversely, the CST group showed nonsignificant strength gains, increasing to significance at postintervention (P≤.003). In both groups, significant pre- to postintervention improvements in mobility outcomes (P≤.03), not retained at follow-up, were observed. Conclusions After 6 weeks of training, CST proved as effective as direct strength training in enhancing performance of the more affected limb with a different time course, which may have practical implications in management of severely weakened limbs where direct strength training is not initially possible.
Abstract.
Puligheddu M, Figorilli M, Laccu I, Congiu P, Gioi G, Tamburrino L, de Natale ER, Ginatempo F, Deriu F, Fantini ML, et al (2017). SEVERITY OF REM SLEEP MUSCLE ATONIA LOSS IN IDIOPATHIC REM SLEEP BEHAVIOUR DISORDER CORRELATES WITH THE DEGREE OF ABNORMALITIES IN THE VESTIBULAR EVOKED MYOGENIC POTENTIALS.
Author URL.
2016
Manca A, Cabboi MP, Ortu E, Ginatempo F, Dragone D, Zarbo IR, de Natale ER, Mureddu G, Bua G, Deriu F, et al (2016). Effect of contralateral strength training on muscle weakness in people with multiple sclerosis: Proof-of-concept case series.
Physical Therapy,
96(6), 828-838.
Abstract:
Effect of contralateral strength training on muscle weakness in people with multiple sclerosis: Proof-of-concept case series
Background. The contralateral strength training (CST) effect is a transfer of muscle performance to the untrained limb following training of the contralateral side. Objective. The aim of this study was to explore, in individuals with multiple sclerosis (MS) presenting marked lower limb strength asymmetry, the effectiveness of CST on management of muscle weakness of the more-affected limb following training of the less-affected limb. Design. A single-subject research design was used. Methods. Eight individuals with MS underwent 16 to 18 high-intensity training sessions of the less-affected ankle dorsiflexor muscles. The primary outcome measure of this single-system case series was maximal strength expressed as peak moment and maximal work. Secondary outcome measures were: Six-Minute-Walk Test, Timed “Up & Go” Test, 10-Meter Timed Walk Test, and Multiple Sclerosis Quality of Life–54 questionnaire. Results. After the 6-week intervention, the contralateral more affected (untrained) limb showed a 22% to 24% increase in maximal strength. From pretest-posttest measurements, participants also performed significantly better on the clinical and functional secondary outcome measures. At the 12-week follow-up, the strength levels of the weaker untrained limb remained significantly superior to baseline levels in the majority (5 out of 8) of the outcome parameters. Limitations. Considering the design used, the absence of a control group, and the sample size, these findings should be cautiously generalized and will need confirmation in a properly planned randomized controlled trial. Conclusions. The present proof-of-concept study shows, for the first time, the occurrence of the CST effect on muscle performance of ankle dorsiflexor muscles in people with MS. These preliminary findings reveal new potential implications for CST as a promising rehabilitation approach to those conditions where unilateral muscle weakness does not allow or makes difficult performing conventional strength training of the weaker limb.
Abstract.
de Natale ER, Ginatempo F, Pilurzi G, Ortu E, Mercante B, Manca A, Magnano I, Tolu E, Rothwell JC, Deriu F, et al (2016). ID 267 – Vestibulo-masseteric reflex and acoustic-masseteric reflex: Normative values. Clinical Neurophysiology, 127(3).
Manca A, Ginatempo F, Cabboi MP, Mercante B, Ortu E, Dragone D, De Natale ER, Dvir Z, Rothwell JC, Deriu F, et al (2016). No evidence of neural adaptations following chronic unilateral isometric training of the intrinsic muscles of the hand: a randomized controlled study.
European Journal of Applied Physiology,
116(10), 1993-2005.
Abstract:
No evidence of neural adaptations following chronic unilateral isometric training of the intrinsic muscles of the hand: a randomized controlled study
Purpose: to test whether long-term cortical adaptations occur bilaterally following chronic unilateral training with a simple motor task. Methods: Participants (n = 34) were randomly allocated to a training or control groups. Only the former completed a 4-week maximal-intensity isometric training of the right first dorsal interosseus muscle through key pinching. Maximal strength was assessed bilaterally in four different movements progressively less similar to the training task: key, tip and tripod pinches, and handgrip. Transcranial magnetic stimulation was used to probe, in the left and right primary hand motor cortices, a number of standard tests of cortical excitability, including thresholds, intra-cortical inhibition and facilitation, transcallosal inhibition, and sensory-motor integration. Results: Training increased strength in the trained hand, but only for the tasks specifically involving the trained muscle (key +8.5 %; p
Abstract.
de Natale ER, Ginatempo F, Manca A, Paulus KS, Agnetti V, Tolu E, Deriu F (2016). Paired neurophysiological and clinical approach to brainstem assessment in Parkinson’s Disease. Clinical Neurophysiology, 127(3).
Deriu F, de Natale ER, Magnano I, Ginatempo F (2016). VEMPs in central neurological disorders. Clinical Neurophysiology, 127(4), 2020-2021.
2015
Manca A, Pisanu F, Ortu E, De Natale ER, Ginatempo F, Dragone D, Tolu E, Deriu F (2015). A comprehensive assessment of the cross-training effect in ankle dorsiflexors of healthy subjects: a randomized controlled study.
Gait and Posture,
42(1), 1-6.
Abstract:
A comprehensive assessment of the cross-training effect in ankle dorsiflexors of healthy subjects: a randomized controlled study
Purpose: to investigate the cross-training effect, induced on ankle dorsiflexors (AD) by unilateral strength-training of the contralateral muscles, as transfer of peak torque (PT) and muscle work (MW) and their relative contributions to muscle performance. Methods: Thirty healthy volunteers were randomly assigned to a training or control group. The trained group sustained a 4-week maximal isokinetic training of the stronger AD at 90 and 45°/s. At both angular velocities, PT, MW and MW/PT ratio were measured from both legs at baseline and after intervention (trained group) or no-intervention (controls). The familiarization/learning-effect was calculated and subtracted by PT and MW measures to obtain their net changes. Results: Net PT increased in both legs (untrained: +27.5% at 90°/s and +17.9% at 45°/s; trained: +15% at 90°/s and +16.3% at 45°/s). Similarly, net MW increased in both the untrained (90°/s: +29.6%; 45°/s: +37%) and trained (90°/s: +23.4%; 45°/s: +18.3%) legs. PT and MW gains were larger in the untrained than trained AD (p< 0.0005), with MW improving more than PT at 45°/s (p= 0.04). The MW/PT ratio increased bilaterally only in the trained group (p< 0.05), depending on the angular velocity. Conclusions: the cross-training effect occurred in AD muscles in terms of both PT and MW, with MW adding valuable information to PT-analysis in describing muscle performance. Moreover, the MW/PT ratio allowed estimating the contributions of these parameters to muscle capability and may represent a novel index in isokinetic testing. The greater improvements in the untrained than trained limb raises interesting clinical implications in asymmetric conditions.
Abstract.
de Natale ER, Ginatempo F, Paulus KS, Pes GM, Manca A, Tolu E, Agnetti V, Deriu F (2015). Abnormalities of vestibular-evoked myogenic potentials in idiopathic Parkinson’s disease are associated with clinical evidence of brainstem involvement.
Neurological Sciences,
36(6), 995-1001.
Abstract:
Abnormalities of vestibular-evoked myogenic potentials in idiopathic Parkinson’s disease are associated with clinical evidence of brainstem involvement
Brainstem degeneration in Parkinson’s disease (PD) may explain the occurrence of many non-motor symptoms in this condition. Purposes of the present work were to investigate brainstem function in PD through a battery of vestibular-evoked myogenic potentials (VEMP) allowing a comprehensive brainstem exploration and to correlate VEMP findings with symptoms related to brainstem involvement. Cervical (cVEMP), masseter (mVEMP) and ocular (oVEMP) VEMPs were investigated in 24 PD patients and compared with those recorded in 24 age-matched controls. Presence of symptoms ascribable to brainstem dysfunction, such as daytime sleepiness, REM sleep behavior disorder and depression, was investigated through Epworth Sleepiness Scale, Parkinson’s Disease Sleep Scale, REM Sleep Disorder Screening Questionnaire (RBD-SQ) and Geriatric Depression Scale. Postural instability was additionally assessed through mini-BESTest. The frequency of alteration of VEMPs in patients was 83.3 % when considering the whole set and 41.7 % for cVEMP, 66.7 % for mVEMP and 45.8 % for oVEMP. This was significantly different from controls, with absence being the prevalent alteration in PD. A significant inverse correlation between the number of altered VEMPs and mini-BESTest and a direct correlation with RBD-SQ were found. The VEMP battery under study allowed the identification of brainstem dysfunctions in PD patients, which correlated with clinical tests suggestive of postural and REM sleep disorders. VEMPs might represent a valuable tool of brainstem assessment in PD.
Abstract.
Manca A, Pisanu F, Ortu E, De Natale E, Ginatempo F, Dragone D, Leali PT, Deriu F (2015). Isokinetic cross-training effect in foot drop following common peroneal nerve injury.
Isokinetics and Exercise Science,
23(1), 17-20.
Abstract:
Isokinetic cross-training effect in foot drop following common peroneal nerve injury
Background: to our knowledge, no studies on foot drop (FD) caused by peripheral nerve lesion have investigated whether unilateral training of the unaffected ankle dorsiflexors induced a clinically meaningful strength improvement in the affected-untrained leg, namely a cross-training (CT) effect. METHOD: a 59-year-old man, who suffered since childhood from surgically-induced damage of the common peroneal nerve, performed an 8-week maximal-intensity isokinetic training of the healthy leg. Before and after training, patient underwent: bilateral isokinetic testing; functional and mobility tests including 6-minute walking test, 10-meter walking test, timed-up-and-go test and ankle ROM; neurophysiological recordings including motor thresholds, cortical silent period of the hemisphere innervating the affected tibialis anterior and mean EMG recruitment. Results: After cross-training, the affected-untrained dorsiflexors showed notable increases in all dynamometric parameters. Similarly, all functional tests improved considerably. The cortical silent period was reduced and the maximal EMG recruitment increased. Conclusions: Improvements in muscle performance and neurophysiological drive in the affected non-trained limb due to training of the unaffected side indicate that cross-training may be a viable rehabilitative approach to foot drop.
Abstract.
de Natale ER, Ginatempo F, Paulus KS, Manca A, Mercante B, Pes GM, Agnetti V, Tolu E, Deriu F (2015). Paired neurophysiological and clinical study of the brainstem at different stages of Parkinson's Disease.
Clinical Neurophysiology,
126(10), 1871-1878.
Abstract:
Paired neurophysiological and clinical study of the brainstem at different stages of Parkinson's Disease
Objective: to study brainstem function in Parkinson's Disease (PD) at different stages, through a battery of vestibular-evoked myogenic potentials (VEMPs) and compare the results with scores on clinical scales assessing the presence of symptoms linked to brainstem involvement. Methods: Cervical, masseter and ocular VEMPs were recorded in patients with early PD (n= 14, disease duration 1.42 ± 0.7. years), advanced PD (n= 19, disease duration 7.26 ± 2.9. years) and in 27 age-matched controls. In PD, the following clinical scales were administered: Mini-BESTest, REM sleep Behavior Disorder Screening Questionnaire (RBD-SQ), PD Sleep Scale, Epworth Sleepiness Scale and Geriatric Depression Scale. Results: Rate of VEMPs alterations was higher (p
Abstract.
2014
Manca A, Ortu E, Ginatempo F, De Natale ER, Pisanu F, Deriu F (2014). P243: Rehabilitation of drop-foot with maximal isokinetic cross-training: a case report. Clinical Neurophysiology, 125
Manca A, Limonta E, Pilurzi G, Ginatempo F, De Natale ER, Mercante B, Tolu E, Deriu F (2014). Ultrasound and Laser as Stand-Alone Therapies for Myofascial Trigger Points: a Randomized, Double-Blind, Placebo-Controlled Study.
Physiotherapy Research International,
19(3), 166-175.
Abstract:
Ultrasound and Laser as Stand-Alone Therapies for Myofascial Trigger Points: a Randomized, Double-Blind, Placebo-Controlled Study
Background and Purpose: Ultrasound (US) and low-level laser therapy (LLLT) are commonly employed for myofascial trigger points (MTP) despite lack of evidence for usage as stand-alone treatments. The aim of the study was to determine, on MTP of the upper trapezius muscle (uTM), the effects of US and LLLT per se, as delivered in accordance with the procedures reported by surveys about their usage among physiotherapists. Methods: Design was set as a double-blind, randomized, placebo-controlled study. Sixty participants with at least one active MTP in uTM (28 women and 32 men; mean age 24.5±1.44years) were recruited and randomly assigned to one out of five groups: active US (n=12), placebo US (n=12), active LLLT (n=11), placebo LLLT (n=11) and no therapy (control, n=14). The participants and outcome assessor were blinded to the group assignment and therapy delivered. Three outcome measures were assessed at baseline, after a 2-week treatment and 12weeks after the end of the intervention (follow-up): pressure pain threshold, subjective pain on a numerical rating scale and muscle extensibility performing a cervical lateral flexion. All subjects assigned to the intervention groups were treated five times weekly for overall 10 treatments given. Two-way ANOVA was used to compare differences before and after intervention and among groups at each time-point. Results: After the 2-week intervention, all groups showed pressure pain threshold, numerical rating scale and cervical lateral flexion significant improvements (p
Abstract.
2012
Paulus KS, Meloni M, Carpentras G, Sassu C, De Natale E, Deriu F, Galistu P, Agnetti V (2012). 4 Parkinson’s disease and conversion disorder: Case report and literature review. Basal Ganglia, 2(4).
