Raffaele Dubbioso

Bio: Raffaele Dubbioso is an academic researcher from University of Naples Federico II. The author has contributed to research in topics: Transcranial magnetic stimulation & Medicine. The author has an hindex of 18, co-authored 69 publications receiving 821 citations. Previous affiliations of Raffaele Dubbioso include University of Copenhagen & Copenhagen University Hospital.

Functional involvement of central cholinergic circuits and visual hallucinations in Parkinson's disease

Abstract: Visual hallucinations (VHs) represent a frequent and disturbing complication of Parkinson's disease. Evidence suggests that VH can be related to central cholinergic dysfunction. Short-latency afferent inhibition (SAI) technique gives the opportunity to test an inhibitory cholinergic circuit in the human cerebral motor cortex. This inhibition of motor-evoked potentials can be observed when transcranial magnetic stimulation is delivered with a delay ranging from 2 to 8 ms, after a peripheral nerve afferent input has reached the somatosensory cortex. We applied SAI technique in 10 non-demented patients with Parkinson's disease with VHs, in 12 non-demented patients with Parkinson's disease without VHs (NVH-pts) and in 11 age-matched normal controls. All patients with Parkinson's disease underwent a battery of neuropsychological tests to assess frontal and visuospatial functions, memory and attention. SAI was significantly reduced in patients with VHs compared with controls and patients without VHs. Neuropsychological examination showed a mild cognitive impairment in 16 out of 22 patients with Parkinson's disease. In addition, we found that in our patients with VHs, performance of some tasks evaluating visuospatial functions and attentional/frontal lobe functions was significantly more impaired than in patients without VHs. SAI abnormalities, presence of VH and neuropsychological results strongly support the hypothesis of cholinergic dysfunction in some patients with Parkinson's disease, who will probably develop a dementia. A follow-up study of our patients is required to verify whether SAI abnormalities can predict a future severe cognitive decline. Moreover, SAI can also be very useful to follow-up the efficacy of anti-cholinesterase therapies.

The effects of prolonged cathodal direct current stimulation on the excitatory and inhibitory circuits of the ipsilateral and contralateral motor cortex

Abstract: Weak cathodal transcranial direct current stimulation (tDCS) of the human hand area modulates corticospinal excitability with a suppression of motor-evoked potentials (MEPs) evoked by transcranial magnetic stimulation (TMS). The changes in excitability persist beyond the time of stimulation if tDCS is given for several minutes and can remain stable for an hour or more. The aim of present study was to evaluate whether a long-lasting suppression of cortical excitability could be induced by prolonged cathodal tDCS (20 min of stimulation). We also explored the impact of brain-derived neurotrophic factor (BDNF) gene polymorphisms, on tDCS after-effects. Cortical excitability to single and paired-pulse TMS was evaluated both for the stimulated and contralateral hemisphere, before and up to 24 h after 20 min of cathodal tDCS. We evaluated threshold and amplitude of MEPs, short interval intracortical inhibition (SICI), and intracortical facilitation (ICF). tDCS produced a pronounced suppression of MEP amplitude that was still significant at 3 h after the end of stimulation. The BDNF genotype had not influence on tDCS after-effects. Thresholds for MEPs, SICI and ICF were not affected. No significant effect was observed in the contralateral hemisphere. Twenty minutes of cathodal tDCS is capable of inducing a long-lasting suppression of the excitability of the human motor cortex.

A cross-sectional study investigating frequency and features of definitely diagnosed diabetic painful polyneuropathy.

Abstract: This cross-sectional multicentre study aimed at investigating frequency and features of painful diabetic polyneuropathy. We consecutively enrolled 816 patients attending hospital diabetic outpatient clinics. We first definitely diagnosed diabetic polyneuropathy and pure small-fibre polyneuropathy using clinical examination, nerve conduction study, and skin biopsy or quantitative sensory testing. Adhering to widely agreed criteria, we then identified neuropathic pain and diagnosed painful polyneuropathy using a combined approach of clinical examination and diagnostic tests. Of the 816 patients, 36% had a diabetic polyneuropathy associated with male sex, age, and diabetes severity; 2.5% of patients had a pure small-fibre polyneuropathy, unrelated to demographic variables and diabetes severity. Of the 816 patients, 115 (13%) suffered from a painful polyneuropathy, with female sex as the only risk factor for suffering from painful polyneuropathy. In this large study, providing a definite diagnosis of diabetic polyneuropathy and pure small-fibre polyneuropathy, we show the frequency of painful polyneuropathy and demonstrate that this difficult-to-treat complication is more common in women than in men.

The therapeutic use of non-invasive brain stimulation in multiple sclerosis - a review.

Abstract: Background Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and a leading cause of disability in young adults. Many disabling symptoms in MS, such as spasticity, pain, depression and cognitive deficits are not fully controlled by drug treatment. Non-invasive brain stimulation (NIBS) techniques can be used as tools for modulating altered cortical excitability and plasticity MS patients, providing an improvement in disabling symptoms affecting such patients. Objective This review reported and summarized some of the most interesting and promising recent achievements regarding the therapeutic use of NIBS in MS patients. Methods We reviewed the clinical application of transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), emphasizing their effect on clinical symptoms and signs that are commonly involved in MS patients. In addition, we shortly described new NIBS protocols, such as transcranial alternating current stimulation and transcranial focused ultrasound stimulation as potential and innovative therapeutic options to be applied in future studies in MS patients. Results We reviewed twenty-one studies covering six main clinical domains. Most of such studies focused on fatigues (33.3%), motor performance (19%) and spasticity (19%), sparse results were about pain (9.5%), cognitive abilities (9.5%), sensory deficit (4.8%) and bladder function (4.8%). The most promising results have been published for the improvement of motor (i.e. hand dexterity) and cognitive performances (i.e. attention and working memory) by applying rTMS or tDCS alone or in association with motor/cognitive training, for pain's treatment by using tDCS. Conclusion There are still no official recommendations for the therapeutic use of tDCS or rTMS in MS. The huge inter-individual variability of NIBS efficacy is still a big challenge which needs to be solved. However, well-designed studies, deeper knowledge about pathomechanisms underlying MS, and the combination of such techniques with motor and cognitive rehabilitation might results in higher effectiveness of NIBS.

[Guillain-Barré syndrome].

Abstract: L'incidence annuelle du syndrome de Guillain-Barre est de 1,5/100000 habitants La mortalite actuelle est estimee a environ 5 % d'apres des essais therapeutiques recents, bien conduits Dix pour cent des malades gardent des sequelles motrices tres invalidantes un an apres le debut des premiers signes neurologiques La prise en charge de ces malades necessite des equipes entrainees, multidisciplinaires, pouvant pratiquer l'ensemble des therapeutiques specifiques La corticotherapie per os'ou par voie intraveineuse est inefficace Les echanges plasmatiques sont le premier traitement dont l'efficacite a ete demontree par rapport a un groupe controle Les indications sont maintenant mieux connues Les formes benignes (marche possible) beneficient de 2 echanges plasmatiques; 2 echanges supplementaires sont realises en cas d'aggravation Dans les formes intermediaires (marche impossible) et les formes severes (recours a la ventilation mecanique), 4 echanges plasmatiques sont conseilles Il n'est pas utile d'augmenter leur nombre dans les formes severes ou en cas d'absence d'amelioration De fortes doses d'immunoglobulines donnees par voie intraveineuse (lq IV) [0,4 g/kg/j pendant 5 jours] sont aussi efficaces que les echanges plasmatiques dans les formes intermediaires et severes Dans ces formes, le choix entre Ig IV et echanges plasmatiques depend des contre-indications respectives de ces traitements et de leur faisabilite Les travaux en cours ont comme objectif de mieux preciser les indications respectives des echanges plasmatiques et des lq IV dans des formes de gravite differente, leur morbidite comparee, la dose optimale des lq IV

Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson's disease

Abstract: Cognitive impairment in patients with Parkinson's disease is gaining increased clinical significance owing to the relative success of therapeutic approaches to the motor symptoms of this disorder. Early investigations contributed to the concept of subcortical dementia associated with bradyphrenia and cognitive rigidity. For cognition in parkinsonian disorders, this notion developed into the concept of mild cognitive impairment and fronto-executive dysfunction in particular, driven mainly by dopaminergic dysmodulation and manifesting as deficits in flexibility, planning, working memory, and reinforcement learning. However, patients with Parkinson's disease could also develop a syndrome of dementia that might depend on non-dopaminergic, cholinergic cortical dysfunction. Recent findings, supplemented by advances in neuroimaging and genetic research, reveal substantial heterogeneity in the range of cognitive deficits in patients with Parkinson's disease. Remediation and management prospects for these cognitive deficits are based on neuropharmacological and cognitive rehabilitation approaches.

BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases

Abstract: Synaptic dysfunction is a key pathophysiological hallmark in several neurodegenerative disorders. In this Review, Lu and colleagues consider a 'synaptic repair'-based therapy for neurodegenerative diseases that targets pathophysiology rather than pathogenesis and discuss BDNF as a potential synaptic repair molecule.