We describe the polysomnographic data of two patients with nocturnal headache attacks fulfilling ... more We describe the polysomnographic data of two patients with nocturnal headache attacks fulfilling the clinical criteria for hypnic headache syndrome. Two overnight polysomnographic studies were performed in each patient. Four nocturnal headache attacks were captured, all emerging from the REM phase of sleep. Our findings suggest a close relationship between the REM phase of sleep and the appearance of hypnic headache attacks.
Subthalamic nucleus deep brain stimulation (STN-DBS) has been recently compared to a possible &am... more Subthalamic nucleus deep brain stimulation (STN-DBS) has been recently compared to a possible "second therapeutic honeymoon" for Parkinson's disease, as it might prevent the development of severe motor complications and lessen the social adjustment associated to disease progression. This study aims to evaluate whether an early surgical treatment could result in better long-term outcomes, comparing the follow-up evolution of 203 parkinsonian patients, treated at different stages of the disease course. The retrospective allocation to Early- or Late-Stimulated groups was performed in accordance to disease severity at the time of surgery and motor fluctuations duration. Then, the two groups clinical outcomes were compared after more than 8 years of follow-up by means of the Unified Parkinson's Disease Rating Scale, reporting the overall disability experienced by patients during the entire observational period. Subjects receiving an earlier STN-DBS showed a sustained improvement in the activities of daily living and motor complications, never reaching the severe levels of disability reported by Late-Stimulated patients at the time of surgical selection. After ≥8 years of follow-up the Early-Stimulated group still reported a 28.7% lower impairment in activities of daily living and 43.8% lower duration of waking day spent in OFF compared to their pre-surgical basal scores. Although the limitation of a retrospective study design should be considered in the interpretation of data, our findings suggest that an earlier STN-DBS treatment might result in a more precocious stabilization of motor complications, with beneficial effects on the patient's social and professional life autonomy.
Patients with advanced Parkinson disease (PD) are at increased risk for asymptomatic leg deep ven... more Patients with advanced Parkinson disease (PD) are at increased risk for asymptomatic leg deep venous thrombosis (DVT) because of severe motor fluctuations. Protracted immobility in the absence of antiparkinsonian therapy during stereotactic surgery may further increase the risk for venous thrombosis. Our aim was to determine the incidence of asymptomatic DVT of leg veins in PD patients undergoing subthalamic nucleus deep brain stimulation (STN-DBS). 41 consecutive PD patients undergoing stereotactic surgery for STN-DBS were investigated by ultrasound compression sonography of leg veins and D-dimer measurement in the week preceding surgery. After surgery, D-dimer measurements were repeated and when the value exceeded the normal range, ultrasound compression sonography was repeated to confirm or exclude DVT. Doppler ultrasonographic examinations demonstrated that 2 patients (4.9%) developed asymptomatic DVT shortly after surgery (8.5 days) despite the fact that none of the 41 patients submitted to STN-DBS had DVT before surgery and that a specific prophylaxis was applied during surgery. Our data show that advanced PD patients are at risk for developing asymptomatic leg DVT following stereotactic surgery performed for STN-DBS. A strict clinical monitoring in the perioperative period is advisable in order to ensure early detection of DVT and prevent further thrombo-embolic complications.
There is increasing evidence of biochemical alterations in peripheral blood lymphocytes of Parkin... more There is increasing evidence of biochemical alterations in peripheral blood lymphocytes of Parkinson's disease (PD) patients. In this work, we describe the changes in protein levels in peripheral lymphocytes of PD patients in order to identify potential peripheral biomarkers. By means of 2D electrophoresis and mass spectrometry protein identification, we compared patients under L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, patients under subthalamic nucleus deep-brain stimulation and healthy controls. Statistical analysis of the results demonstrated that cofilin-1, tropomyosin, and a specific actin isoform vary significantly in patients, regardless of the therapy. Two different isoforms of gamma-fibrinogen either correlate with the disease state or with the disease duration. Eventually, specific changes associated with the different therapies allowed to highlight oxidative stress conditions in lymphocytes in patients treated with higher doses of L-DOPA. As a whole, peripheral blood lymphocytes are sensitive reporters of PD over inter-individual variability, and allow the identification of specific alterations that could be further exploited for diagnostic purposes.
Subthalamic nucleus deep brain stimulation (STN-DBS) and levodopa/carbidopa enteral (Duodopa) inf... more Subthalamic nucleus deep brain stimulation (STN-DBS) and levodopa/carbidopa enteral (Duodopa) infusion are two effective therapeutic options for the treatment of advanced Parkinson's disease (PD). Retrospectively, this study compared the two procedures, evaluating 40 PD patients who underwent either STN-DBS or a percutaneous gastrostomy (PEG) for Duodopa infusion. Duodopa group comprised 20 patients, with a mean follow-up of ∼15 months, treated by Duodopa infusion rather than STN-DBS because of the presence of neurosurgical contraindications, age > 70 years-old, moderate cognitive impairment or patient's unwillingness to undergo neurosurgery. The STN-DBS group comprised 20 consecutive patients similar to the patients of the Duodopa group for age at the disease onset, age at the procedure, follow-up, and duration of motor complications. The only difference concerned neuropsychological functions, which were more impaired in the group of Duodopa patients. Clinical and neuropsychological data were compared at baseline and at follow-up for the two procedures. Both procedures showed a significant improvement in UPDRS-II, UPDRS-III, and UPDRS-IV and a considerable reduction in the percentage of waking day spent in "off," whereas only the STN-DBS group showed a significant improvement in dyskinesias duration and disability. STN-DBS was associated to a significant drop in the phonemic verbal fluency score, whereas Duodopa patients showed a milder worsening in this task. The procedure-related complications occurred more frequently with Duodopa. STN-DBS and Duodopa showed a significant efficacy on motor symptoms, activities of daily living, and motor complications. The group of Duodopa-treated patients developed more procedure-related complications.
The objectives of this study were to evaluate the risk of neuropathy in patients with Parkinson&a... more The objectives of this study were to evaluate the risk of neuropathy in patients with Parkinson's disease (PD) and to evaluate the role of levodopa exposure as a potential risk factor. A multicenter study of 330 patients with PD and 137 healthy controls with a comparable age distribution was performed. With respect to levodopa exposure, 144 patients had long exposure (≥ 3 years) to levodopa (LELD), 103 patients had short exposure (<3 years) to levodopa (SELD), and 83 patients had no exposure to levodopa (NOLD). Nerve function was evaluated using the reduced total neuropathy score. Right sural sensory antidromic and peroneal motor nerve conduction studies were performed by neurophysiologists who were blinded to the existence of neuropathy clinical features or PD treatment. Overall, 19.40% of patients in the LELD group, 6.80% in the SELD group, 4.82% in the NOLD group, and 8.76% in the control group were diagnosed with neuropathy (axonal, predominantly sensory). Multivariate logistic analysis indicated that the risk of neuropathy was not influenced by disease duration, severity, or sex. The risk of neuropathy increased by approximately 8% for each year of age (P < 0.001; odds ratio [OR], 1.08; 95% confidence interval [CI], 1.037-1.128). The risk of neuropathy was 2.38 higher in the LELD group than in the control group (P = 0.022; OR, 2.38; 95% CI, 1.130-5.014). In a comparison between patients with and without neuropathy (Student's t test), the levodopa dose was higher (P < 0.0001), serum vitamin B12 levels were lower (P = 0.0102), and homocysteine levels were higher (P < 0.001) in the patients with neuropathy. Our results demonstrate that the duration of exposure to levodopa, along with age, is the main risk factor for the development of neuropathy. Screening for homocysteine and vitamin B12 levels and clinical-neurophysiological monitoring for neuropathy may be advisable in patients with PD who are receiving treatment with levodopa.
We describe the polysomnographic data of two patients with nocturnal headache attacks fulfilling ... more We describe the polysomnographic data of two patients with nocturnal headache attacks fulfilling the clinical criteria for hypnic headache syndrome. Two overnight polysomnographic studies were performed in each patient. Four nocturnal headache attacks were captured, all emerging from the REM phase of sleep. Our findings suggest a close relationship between the REM phase of sleep and the appearance of hypnic headache attacks.
Subthalamic nucleus deep brain stimulation (STN-DBS) has been recently compared to a possible &am... more Subthalamic nucleus deep brain stimulation (STN-DBS) has been recently compared to a possible "second therapeutic honeymoon" for Parkinson's disease, as it might prevent the development of severe motor complications and lessen the social adjustment associated to disease progression. This study aims to evaluate whether an early surgical treatment could result in better long-term outcomes, comparing the follow-up evolution of 203 parkinsonian patients, treated at different stages of the disease course. The retrospective allocation to Early- or Late-Stimulated groups was performed in accordance to disease severity at the time of surgery and motor fluctuations duration. Then, the two groups clinical outcomes were compared after more than 8 years of follow-up by means of the Unified Parkinson's Disease Rating Scale, reporting the overall disability experienced by patients during the entire observational period. Subjects receiving an earlier STN-DBS showed a sustained improvement in the activities of daily living and motor complications, never reaching the severe levels of disability reported by Late-Stimulated patients at the time of surgical selection. After ≥8 years of follow-up the Early-Stimulated group still reported a 28.7% lower impairment in activities of daily living and 43.8% lower duration of waking day spent in OFF compared to their pre-surgical basal scores. Although the limitation of a retrospective study design should be considered in the interpretation of data, our findings suggest that an earlier STN-DBS treatment might result in a more precocious stabilization of motor complications, with beneficial effects on the patient's social and professional life autonomy.
Patients with advanced Parkinson disease (PD) are at increased risk for asymptomatic leg deep ven... more Patients with advanced Parkinson disease (PD) are at increased risk for asymptomatic leg deep venous thrombosis (DVT) because of severe motor fluctuations. Protracted immobility in the absence of antiparkinsonian therapy during stereotactic surgery may further increase the risk for venous thrombosis. Our aim was to determine the incidence of asymptomatic DVT of leg veins in PD patients undergoing subthalamic nucleus deep brain stimulation (STN-DBS). 41 consecutive PD patients undergoing stereotactic surgery for STN-DBS were investigated by ultrasound compression sonography of leg veins and D-dimer measurement in the week preceding surgery. After surgery, D-dimer measurements were repeated and when the value exceeded the normal range, ultrasound compression sonography was repeated to confirm or exclude DVT. Doppler ultrasonographic examinations demonstrated that 2 patients (4.9%) developed asymptomatic DVT shortly after surgery (8.5 days) despite the fact that none of the 41 patients submitted to STN-DBS had DVT before surgery and that a specific prophylaxis was applied during surgery. Our data show that advanced PD patients are at risk for developing asymptomatic leg DVT following stereotactic surgery performed for STN-DBS. A strict clinical monitoring in the perioperative period is advisable in order to ensure early detection of DVT and prevent further thrombo-embolic complications.
There is increasing evidence of biochemical alterations in peripheral blood lymphocytes of Parkin... more There is increasing evidence of biochemical alterations in peripheral blood lymphocytes of Parkinson's disease (PD) patients. In this work, we describe the changes in protein levels in peripheral lymphocytes of PD patients in order to identify potential peripheral biomarkers. By means of 2D electrophoresis and mass spectrometry protein identification, we compared patients under L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, patients under subthalamic nucleus deep-brain stimulation and healthy controls. Statistical analysis of the results demonstrated that cofilin-1, tropomyosin, and a specific actin isoform vary significantly in patients, regardless of the therapy. Two different isoforms of gamma-fibrinogen either correlate with the disease state or with the disease duration. Eventually, specific changes associated with the different therapies allowed to highlight oxidative stress conditions in lymphocytes in patients treated with higher doses of L-DOPA. As a whole, peripheral blood lymphocytes are sensitive reporters of PD over inter-individual variability, and allow the identification of specific alterations that could be further exploited for diagnostic purposes.
Subthalamic nucleus deep brain stimulation (STN-DBS) and levodopa/carbidopa enteral (Duodopa) inf... more Subthalamic nucleus deep brain stimulation (STN-DBS) and levodopa/carbidopa enteral (Duodopa) infusion are two effective therapeutic options for the treatment of advanced Parkinson's disease (PD). Retrospectively, this study compared the two procedures, evaluating 40 PD patients who underwent either STN-DBS or a percutaneous gastrostomy (PEG) for Duodopa infusion. Duodopa group comprised 20 patients, with a mean follow-up of ∼15 months, treated by Duodopa infusion rather than STN-DBS because of the presence of neurosurgical contraindications, age > 70 years-old, moderate cognitive impairment or patient's unwillingness to undergo neurosurgery. The STN-DBS group comprised 20 consecutive patients similar to the patients of the Duodopa group for age at the disease onset, age at the procedure, follow-up, and duration of motor complications. The only difference concerned neuropsychological functions, which were more impaired in the group of Duodopa patients. Clinical and neuropsychological data were compared at baseline and at follow-up for the two procedures. Both procedures showed a significant improvement in UPDRS-II, UPDRS-III, and UPDRS-IV and a considerable reduction in the percentage of waking day spent in "off," whereas only the STN-DBS group showed a significant improvement in dyskinesias duration and disability. STN-DBS was associated to a significant drop in the phonemic verbal fluency score, whereas Duodopa patients showed a milder worsening in this task. The procedure-related complications occurred more frequently with Duodopa. STN-DBS and Duodopa showed a significant efficacy on motor symptoms, activities of daily living, and motor complications. The group of Duodopa-treated patients developed more procedure-related complications.
The objectives of this study were to evaluate the risk of neuropathy in patients with Parkinson&a... more The objectives of this study were to evaluate the risk of neuropathy in patients with Parkinson's disease (PD) and to evaluate the role of levodopa exposure as a potential risk factor. A multicenter study of 330 patients with PD and 137 healthy controls with a comparable age distribution was performed. With respect to levodopa exposure, 144 patients had long exposure (≥ 3 years) to levodopa (LELD), 103 patients had short exposure (<3 years) to levodopa (SELD), and 83 patients had no exposure to levodopa (NOLD). Nerve function was evaluated using the reduced total neuropathy score. Right sural sensory antidromic and peroneal motor nerve conduction studies were performed by neurophysiologists who were blinded to the existence of neuropathy clinical features or PD treatment. Overall, 19.40% of patients in the LELD group, 6.80% in the SELD group, 4.82% in the NOLD group, and 8.76% in the control group were diagnosed with neuropathy (axonal, predominantly sensory). Multivariate logistic analysis indicated that the risk of neuropathy was not influenced by disease duration, severity, or sex. The risk of neuropathy increased by approximately 8% for each year of age (P < 0.001; odds ratio [OR], 1.08; 95% confidence interval [CI], 1.037-1.128). The risk of neuropathy was 2.38 higher in the LELD group than in the control group (P = 0.022; OR, 2.38; 95% CI, 1.130-5.014). In a comparison between patients with and without neuropathy (Student's t test), the levodopa dose was higher (P < 0.0001), serum vitamin B12 levels were lower (P = 0.0102), and homocysteine levels were higher (P < 0.001) in the patients with neuropathy. Our results demonstrate that the duration of exposure to levodopa, along with age, is the main risk factor for the development of neuropathy. Screening for homocysteine and vitamin B12 levels and clinical-neurophysiological monitoring for neuropathy may be advisable in patients with PD who are receiving treatment with levodopa.
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Papers by Maurizio Zibetti