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"Contardi, Sara"
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Long-term effects of subthalamic nucleus deep brain stimulation on speech in Parkinson’s disease
by
Fraix, Valérie
,
Di Rauso, Giulia
,
Menozzi, Elisa
in
692/617/375/346
,
692/617/375/346/1718
,
Deep brain stimulation
2023
Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment in advanced Parkinson’s Disease (PD). However, the effects of STN-DBS on speech are still debated, particularly in the long-term follow-up. The objective of this study was to evaluate the long-term effects of bilateral STN-DBS on speech in a cohort of advanced PD patients treated with bilateral STN-DBS. Each patient was assessed before surgery through a neurological evaluation and a perceptual-acoustic analysis of speech and re-assessed in the long-term in different stimulation and drug conditions. The primary outcome was the percentage change of speech intelligibility obtained by comparing the postoperative on-stimulation/off-medication condition with the preoperative off-medication condition. Twenty-five PD patients treated with bilateral STN-DBS with a 5-year follow-up were included. In the long-term, speech intelligibility stayed at the same level as preoperative values when compared with preoperative values. STN-DBS induced a significant acute improvement of speech intelligibility (p < 0.005) in the postoperative assessment when compared to the on-stimulation/off-medication and off-stimulation/off-medication conditions. These results highlight that STN-DBS may handle speech intelligibility even in the long-term.
Journal Article
Multicentre case-control study on the association between COVID-19 vaccines and neurological disorders (COVIVAX)
2025
The COVIVAX study assessed the association between COVID-19 vaccination and the risk of common neurological disorders in a multicenter case-control design. Vaccination exposure was compared between individuals with a first diagnosis of a neurological disorder (cases) and age- and sex-matched controls. A total of 624 participants were enrolled, and after random 1:1 matching 265 cases and 265 matched controls (total 530 participants) were included in the analyses. The most frequent neurological diagnosis in cases were stroke (60.4%), multiple sclerosis (11.3%) and seizures (6.4%). The proportion of vaccinated participants was 72.1% among cases and 79.6% among controls. A protective role of vaccination on the risk of developing a new neurological disorder was detected in the unadjusted analysis (OR 0.50; 95% CI 0.29–0.86;
p
= 0.0114). After adjustment for confounders, the number of vaccination doses received was associated with a reduced risk of developing new neurological disorders for participants aged over 60 years (
p
= 0.0472; OR 0.14, 95% CI 0.03–0.68), with pre-existing comorbidities (
p
= 0.0122; OR 0.04, 95% CI 0.01–0.99) and for stroke (
p
= 0.0232; OR 0.04, 95% CI 0.02–0.97). The COVIVAX study provided no warning sign regarding an increase in the risk of developing new neurological disorders following COVID-19 vaccination of any type or doses. A potentially protective effect of multiple doses of COVID-19 vaccines against the risk of stroke in people aged over 60 needs to be confirmed by further studies.
Journal Article
MRI Correlates of Parkinson's Disease Progression: A Voxel Based Morphometry Study
by
Benuzzi, Francesca
,
Nichelli, Paolo
,
Codeluppi, Luca
in
Brain research
,
Care and treatment
,
Development and progression
2015
We investigated structural brain differences between a group of early-mild PD patients at different phases of the disease and healthy subjects using voxel-based morphometry (VBM). 20 mild PD patients compared to 15 healthy at baseline and after 2 years of follow-up. VBM is a fully automated technique, which allows the identification of regional differences in the gray matter enabling an objective analysis of the whole brain between groups of subjects. With respect to controls, PD patients exhibited decreased GM volumes in right putamen and right parietal cortex. After 2 years of disease, the same patients confirmed GM loss in the putamen and parietal cortex; a significant difference was also observed in the area of pedunculopontine nucleus (PPN) and in the mesencephalic locomotor region (MLR). PD is associated with brain morphological changes in cortical and subcortical structures. The first regions to be affected in PD seem to be the parietal cortex and the putamen. A third structure that undergoes atrophy is the part of the inferior-posterior midbrain, attributable to the PPN and MLR. Our findings provide new insight into the brain involvement in PD and could contribute to a better understanding of the sequence of events occurring in these patients.
Journal Article
Freezing of Gait in Parkinson’s Disease Patients Treated with Bilateral Subthalamic Nucleus Deep Brain Stimulation: A Long-Term Overview
by
Fraix, Valerie
,
Di Rauso, Giulia
,
Pavesi, Giacomo
in
Akinesia
,
Alzheimer's disease
,
axial symptoms
2022
Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment in advanced Parkinson’s Disease (PD). However, the effects of STN-DBS on freezing of gait (FOG) are still debated, particularly in the long-term follow-up (≥5-years). The main aim of the current study is to evaluate the long-term effects of STN-DBS on FOG. Twenty STN-DBS treated PD patients were included. Each patient was assessed before surgery through a detailed neurological evaluation, including FOG score, and revaluated in the long-term (median follow-up: 5-years) in different stimulation and drug conditions. In the long term follow-up, FOG score significantly worsened in the off-stimulation/off-medication condition compared with the pre-operative off-medication assessment (z = −1.930; p = 0.05) but not in the on-stimulation/off-medication (z = −0.357; p = 0.721). There was also a significant improvement of FOG at long-term assessment by comparing on-stimulation/off-medication and off-stimulation/off-medication conditions (z = −2.944; p = 0.003). These results highlight the possible beneficial long-term effects of STN-DBS on FOG.
Journal Article
Can Disruption of Basal Ganglia-Thalamocortical Circuit in Wilson Disease Be Associated with Juvenile Myoclonic Epilepsy Phenotype?
by
Benuzzi, Francesca
,
Ferrara, Francesca
,
Pietrangelo, Antonello
in
Ataxia
,
Basal ganglia
,
Brain mapping
2022
In this paper, we describe the multimodal MRI findings in a patient with Wilson disease and a seizure disorder, characterized by an electroclinical picture resembling juvenile myoclonic epilepsy. The brain structural MRI showed a deposition of ferromagnetic materials in the basal ganglia, with marked hypointensities in T2-weighted images of globus pallidus internus bilaterally. A resting-state fMRI study revealed increased functional connectivity in the patient, compared to control subjects, in the following networks: (1) between the primary motor cortex and several cortical regions, including the secondary somatosensory cortex and (2) between the globus pallidus and the thalamo-frontal network. These findings suggest that globus pallidus alterations, due to metal accumulation, can lead to a reduction in the normal globus pallidus inhibitory tone on the thalamo-(motor)-cortical pathway. This, in turn, can result in hyperconnectivity in the motor cortex circuitry, leading to myoclonus and tonic-clonic seizures. We suppose that, in this patient, Wilson disease generated a ‘lesion model’ of myoclonic epilepsy.
Journal Article
Epilepsy Stands Nearby: A Pilot CT Perfusion Study on Post‐Stroke Non‐Convulsive Status Epilepticus
by
Zini, Andrea
,
Merli, Elena
,
Testoni, Stefania
in
Aged
,
Aged, 80 and over
,
brain perfusion imaging
2025
Background To investigate the relevance of hyperperfusion on computerised perfusion imaging (CTP) in the emergency setting in people with non‐convulsive status epilepticus (NCSE) and previous stroke, to derive relevant aspects on the epileptogenic focus and the network recruited for NCSE propagation. Methods We enrolled consecutive adult patients with acute‐onset NCSE and a previous stroke at a single institution undergoing CTP and EEG during symptoms. All patients underwent standard imaging including CT, CTP, CT angiograms and standard EEG within 30 min from hospital arrival. Age‐/sex‐matched NCSE without previous stroke cases and recurrent ischaemic stroke cases were included to test for accuracy of hyperperfusion rates. Results Overall, 15 patients had a previous stroke and developed NCSE (mean age 78 years, 46.7% female). All patients had hyperperfusion on CTP imaging (mean onset‐to‐CTP 184 min). Only one case showed hyperperfusion limited to the previous stroke lesion, and one had a combination of lesional and peri‐lesional hyperperfusion. All remaining cases (n = 13) had exclusive extra‐lesional involvement. Five cases had multiple separated hyperperfused areas, and five had ipsilateral intra‐thalamic hyperperfusion. No correlation emerged between onset‐to‐CTP timing and hyperperfusion (p value for CTP = 0.66, CBV = 0.28, MTT = 0.28, reverse Tmax = 0.66). Hyperperfusion was present in NCSE cases only and in none of age‐/sex‐matched ischaemic stroke cases (n = 18). Conclusions Hyperperfusion involves cortical areas external to the previous lesion site during NCSE, supporting the relevance of networks for the spatial evolution of epileptic activity and limited relevance of the lesion site for the propagation of the epileptiform activity.
Journal Article
Pragmatic computerised perfusion diagnostics for non-convulsive status epilepticus: a prospective observational study
2024
BackgroundNon-convulsive status epilepticus (NCSE) is a time-dependent neurological disorder often misdiagnosed in the emergency setting. Electroencephalography (EEG) is often not available on a 24/7 basis, and Salzburg criteria may at times miss the diagnosis. Here, we tested the accuracy of hyperperfusion on CT perfusion imaging (CTP) in the identification of NCSE against Salzburg criteria, to define its potential role in a pragmatic diagnostic workflow.MethodsWe enrolled consecutive patients with suspected acute seizure or seizure disorder undergoing brain imaging with CTP and EEG from January 2021 to March 2023. EEG recordings, Salzburg criteria and CTP hyperperfusion were rated and adjudicated by two independent experts blinded to patient status. A reference standard including all clinical, lab, imaging, EEG and therapeutic data was used to adjudicate NCSE diagnosis. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values (NPV) were calculated for CTP hyperperfusion and Salzburg criteria versus NCSE adjudicated according to reference standard.ResultsSeventy-seven patients were enrolled. Among 21 NCSE cases, 17 were adjudicated according to Salzburg criteria (81%) and 4 received NCSE diagnosis according to reference standard. Agreement between EEG and CTP emerged in 16/21 NCSE cases, reaching sublobar level in 37.5% of cases. Receiver operator curve analysis suggested good accuracy for CTP hyperperfusion for the diagnosis of NCSE (AUROC 0.79, 95% CI 0.69 to 0.89). CTP hyperperfusion had a high NPV for NCSE (NPV 0.97, 95% CI 0.86 to 1).ConclusionCTP hyperperfusion may be implemented in the emergency fast-track to rule out NCSE, given very high NPV. Further validation studies are needed to evaluate CTP application in real-world setting for NCSE codes.
Journal Article
Long-term effects of bilateral subthalamic nucleus deep brain stimulation on gait disorders in Parkinson’s disease: a clinical-instrumental study
by
Guagnano, Noemi
,
Fraix, Valérie
,
Di Rauso, Giulia
in
Cognitive science
,
Deep brain stimulation
,
Deep Brain Stimulation - methods
2023
Objective
To assess the long-term effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on gait in a cohort of advanced Parkinson’s Disease (PD) patients.
Methods
This observational study included consecutive PD patients treated with bilateral STN-DBS. Different stimulation and drug treatment conditions were assessed: on-stimulation/off-medication, off-stimulation/off-medication, and on-stimulation/on-medication. Each patient performed the instrumented Timed Up and Go test (iTUG). The instrumental evaluation of walking ability was carried out with a wearable inertial sensor containing a three-dimensional (3D) accelerometer, gyroscope, and magnetometer. This device could provide 3D linear acceleration, angular velocity, and magnetic field vector. Disease motor severity was evaluated with the total score and subscores of the Unified Parkinson Disease Rating Scale part III.
Results
Twenty-five PD patients with a 5-years median follow-up after surgery (range 3–7) were included (18 men; mean disease duration at surgery 10.44 ± 4.62 years; mean age at surgery 58.40 ± 5.73 years). Both stimulation and medication reduced the total duration of the iTUG and most of its different phases, suggesting a long-term beneficial effect on gait after surgery. However, comparing the two treatments, dopaminergic therapy had a more marked effect in all test phases. STN-DBS alone reduced total iTUG duration, sit-to-stand, and second turn phases duration, while it had a lower effect on stand-to-sit, first turn, forward walking, and walking backward phases duration.
Conclusions
This study highlighted that in the long-term after surgery, STN-DBS may contribute to gait and postural control improvement when used together with dopamine replacement therapy, which still shows a substantial beneficial effect.
Journal Article
Combined Central and Peripheral Demyelination with Anti-Neurofascin155 IgG Following COVID-19 Vaccination
by
Merli, Elena
,
Gabrielli, Liliana
,
Descovich, Carlo
in
Antibodies
,
Cerebrospinal fluid
,
COVID-19
2023
ADEM = acute demyelinating encephalomyelitis; CE = contrast enhancement; CSF = cerebrospinal fluid; CNS = central nervous system; DADS = distal acquired demyelinating symmetric neuropathy; EMG = electromyography and nerve conduction study; IL = interleukin; IVIg = intravenous immunoglobulin; PNS = peripheral nervous system. [...]finding seems to replicate the mechanisms of autoimmune-mediated complications of vaccination2 and is in accordance with data from a large CCPD case series, where recent vaccination/infection triggered two-thirds of cases.1 Peripheral nervous system (PNS) involvement can happen before, hand-in-hand with, or after central nervous system (CNS) involvement1,3,4 and influences the first treatment choice, as those with early PNS involvement might receive IVIg/plasmapheresis rather than steroids.1,4 CCPD has also been reported with anti-NF155 autoantibodies.3,4 This case exhibits some of the characteristic features of CCPD with anti-NF155 antibodies: the MS-like CNS involvement, with perivenular inflammation at periventricular sites (Figure 1D); absence of oligoclonal bands in CSF; damage in nerve roots and DADS.4 An attempt to better characterize the patient’s immune response has been made by measuring cytokines levels both on serum and on CSF across the stay. Here, although the temporal association of CCPD and vaccination does not prove any causal link, a connection with vaccine exposure must be considered, given the very rare nature of the syndrome and the negative findings emerging from all investigations.
Journal Article