Papers by Michele Feleppa
Diseases (Basel, Switzerland), Jan 4, 2018
The aim of this study was to assess the role of Action Observation (AO) to improve balance, gait,... more The aim of this study was to assess the role of Action Observation (AO) to improve balance, gait, reduce falls, and to investigate the changes in P300 pattern. Five cognitively intact People with Parkinson’s disease (PwP) were enrolled in this prospective, quasi-experimental study to undergo a rehabilitation program of AO for gait and balance recovery of 60 min, three times a week for four weeks. The statistical analysis showed significant improvements for Unified Parkinson’s Disease Rating Scale (UPDRS) motor section III = 0.0082, Short form 12-items Healthy Survey (SF-12) Mental Composite Score (MCS) = 0.0007, Freezing of gait Questionnaire (FOG-Q) = 0.0030, The 39-items Parkinson’s Disease Questionnaire (PDQ-39) = 0.100, and for P300ld = 0.0077. In conclusion, AO reveals to be a safe and feasible paradigm of rehabilitative exercise in cognitively preserved PwP.
Primary Headaches in an Elderly Population Seeking Medical Care for Cognitive Decline
Headache, 2017
To assess the prevalence of specific headache disorders in a population older than 65 years seeki... more To assess the prevalence of specific headache disorders in a population older than 65 years seeking consultation due to memory problems or cognitive impairment. We verified the occurrence of headache symptoms and the impact of headaches on daily life. Headaches were classified as per the International Classification of Headache Disorders, 2nd edition (ICHD-2). All patients were screened with the Mini-Mental State Examination (MMSE), followed by the Selective Reminding Test and neuroimaging. Participants with severe cognitive impairment or dementia were excluded. A total of 1,237 patients (51.6% women), with mean age of 75.6 years (SD = 6.9) were screened from January 2006 to December 2014. Of them, 302 (24.4%) patients suffered from headaches. Most common individual diagnoses were probable migraine (13.8%), episodic tension-type headache (3.4%), and episodic migraine (3.0%). Chronic migraine or probable chronic migraine happened in 3.5%, while chronic tension-type headache affected ...
Headaches of rhinogenic origin illustrate an interesting paradox. Little is known about their pat... more Headaches of rhinogenic origin illustrate an interesting paradox. Little is known about their pathophysiology, mechanisms, and prevalence; yet, the concept that these headaches are of importance is widely accepted. This article discusses the relationship between fronto-turbinalis sinus expansion and headaches, as well as headache outcomes after surgical approach.
Cerebral Venous Thrombosis and Headache - A Case-Series
Headache, 2015
Headache happens in the majority of patients with Cerebral Venous Thrombosis (CVT) being sometime... more Headache happens in the majority of patients with Cerebral Venous Thrombosis (CVT) being sometimes the sole manifestation of the disease. Herein we report a case-series of CVT, focusing on headache characteristics. Etiological, clinical, and radiological features of 25 consecutive adult patients with CVT were compiled from August 2005 to December 2013. Diagnosis of CVT was confirmed by brain magnetic resonance imaging and magnetic resonance venography. All patients underwent extensive systematic etiological and genetic work-up at admission. A structured questionnaire about the characteristics of headache was responded by all participants. Headache was reported by 23 out of 25 (92%) of participants, being by far the most frequent symptom. It was the sole manifestation in nearly one third of the patients (8/25, 32.0%). Headache was typically severe (19/23, 82.6%) and throbbing (16/23, 69.5%), with sudden onset (13/23, 56.5%) and non-remitting (20/23, 86.9%) characteristics. The sinus ...
Friedreich's ataxia: Oxidative stress and cytoskeletal abnormalities
Journal of the Neurological Sciences, 2009
Friedreich&am... more Friedreich's ataxia (FRDA) is an autosomal recessive disorder caused by mutations in the gene encoding frataxin, a mitochondrial protein implicated in iron metabolism. Current evidence suggests that loss of frataxin causes iron overload in tissues, and increase in free-radical production leading to oxidation and inactivation of mitochondrial respiratory chain enzymes, particularly Complexes I, II, III and aconitase. Glutathione plays an important role in the detoxification of ROS in the Central Nervous System (CNS), where it also provides regulation of protein function by glutathionylation. The cytoskeletal proteins are particularly susceptible to oxidation and appear constitutively glutathionylated in the human CNS. Previously, we showed loss of cytoskeletal organization in fibroblasts of patients with FRDA found to be associated with increased levels of glutathione bound to cytoskeletal proteins. In this study, we analysed the glutathionylation of proteins in the spinal cord of patients with FRDA and the distribution of tubulin and neurofilaments in the same area. We found, for the first time, a significant rise of the dynamic pool of tubulin as well as abnormal distribution of the phosphorylated forms of human neurofilaments in FRDA motor neurons. In the same cells, the cytoskeletal abnormalities co-localized with an increase in protein glutathionylation and the mitochondrial proteins were normally expressed by immunocytochemistry. Our results suggest that in FRDA oxidative stress causes abnormally increased protein glutathionylation leading to prominent abnormalities of the neuronal cytoskeleton.
Headache: The Journal of Head and Face Pain, 1999
A multicenter 3-year follow-up study was carried out on young patients with headache referred to ... more A multicenter 3-year follow-up study was carried out on young patients with headache referred to tertiary headache centers or pediatric clinics. Three years after the first examination in 1993,442 (of an original sample of 719) young outpatients with headache (226 females and 216 males) were re-examined. The diagnostic criteria of the International Headache Society (IHS) and those modified for migraine without aura by Winner et al were applied at both the baseline evaluation and the 3-year re-examination. At the follow-up, 290 children still had headache, 101 were in clinical remission, and 51 had dropped out. Using the current diagnostic criteria, only 46.2% of patients having migraine without aura, 50% of those having migraine with aura, and 35.3% of those suffering from migraine disorders which do not fulfill IHS criteria for migraine received the same diagnosis at the time of followup. The percentage of patients receiving a diagnosis of migraine without aura rose significantly when new modified criteria were used (60.5%), whereas a drop in the frequency of migraine disorders not fulfilling IHS criteria was observed at follow-up, both in patients with the diagnosis of migraine without aura at the first examination (4.4%) and in patients with migraine not always fulfilling IHS criteria at the first examination (4.2%). Among all patients who received this latter diagnosis at the first examination, it was possible to make a diagnosis of migraine with aura at the follow-up in 8.8% of cases and that of migraine without aura in 26.5%.
Assessment of Adverse Events Associated With Triptans-Methods of Assessment Influence the Results
Headache: The Journal of Head and Face Pain, 2004
A recent study conducted in triptan-naive migraine patients showed that tolerability was the seco... more A recent study conducted in triptan-naive migraine patients showed that tolerability was the second most important attribute of an acute treatment. However, the proportion of patients reporting side effects after any acute treatment may vary with regard to the method of assessment. To contrast two methods of assessing adverse events (prompted and unprompted) in those with headache using triptans. This study was conducted in two sites, a headache center in the United States, and a neurology office focusing on headache in Italy. We prospectively surveyed 415 adults with headache, who had been using the same triptan for at least 3 months. Participants were asked about their headache and treatment history. Subjects then completed a standardized questionnaire, assessing adverse events in two different ways. First, subjects were asked if they had any adverse events when using the triptan. After returning the first part of the questionnaire, subjects received a second form, where 49 possible adverse events were listed. We contrasted and correlated both sets of answers. Most patients (U.S.=74.9%, Italy=65.5%) reported no side effects in the unprompted questionnaire. However, most of them (U.S.=62.9%, Italy=54.1%) reported at least one side effect in the prompted questionnaire. Most patients that reported side effects in the unprompted questionnaire said they had just one adverse event, while most reported two or more side effects in the prompted questionnaire. Both in the unprompted and in the prompted questionnaires, most side effects were rated as mild or moderate. Interestingly, 31 (7.5%) subjects (pooling data from both sites together) graded their adverse events as severe in the prompted questionnaire, but had not self-reported them. (1) When assessing adverse events, the method of data collection may dramatically influence the results. (2) From those subjects who did not self-report adverse events after using a triptan, most of them will report positively if presented with a list of side effects.
Current Pain and Headache Reports, 2011
Headaches of rhinogenic origin illustrate an interesting paradox. Little is known about their pat... more Headaches of rhinogenic origin illustrate an interesting paradox. Little is known about their pathophysiology, mechanisms, and prevalence; yet, the concept that these headaches are of importance is widely accepted. This article discusses the relationship between fronto-turbinalis sinus expansion and headaches, as well as headache outcomes after surgical approach.
Cephalalgia, 2006
A population-based longitudinal study suggests that obesity is a strong risk factor for the devel... more A population-based longitudinal study suggests that obesity is a strong risk factor for the development of headaches on 15 or more days per month. Little is know about the influence of weight on the response to headache preventive treatment. Herein we prospectively assessed the influence of the baseline body mass index (BMI) on the response to headache preventive treatment. We included adults with episodic or chronic migraine (ICHD-2), or transformed migraine (Silberstein and Lipton criteria) that sought care in a headache clinic. BMI was assessed in the first visit. Baseline information included headache frequency, number of days with severe headache (prospectively obtained over 1 month), and headache-related disability (HIT-6). The same information was obtained after 3 months of preventive treatment. Subjects were categorized based on BMI in: normal weight (≤24.9), overweight (25-29.9), or obese (≥30). We contrasted the headache end-points using ANOVA with post-test and Kruskal-Wa...
Cephalalgia, 2006
The molecular basis of migraine is still not completely understood. An impairment of mitochondria... more The molecular basis of migraine is still not completely understood. An impairment of mitochondrial oxidative metabolism might play a role in the pathophysiology of this disease, by influencing neuronal information processing. Biochemical assays of platelets and muscle biopsies performed in migraine sufferers have shown a decreased activity of the respiratory chain enzymes. Studies with phosphorus magnetic resonance spectroscopy ( 31 P-MRS) have demonstrated an impairment of the brain oxidative energy metabolism both during and between migraine attacks. However, molecular genetic studies have not detected specific mitochondrial DNA (mtDNA) mutations in patients with migraine, although other studies suggest that particular genetic markers (i.e. neutral polymorphisms or secondary mtDNA mutations) might be present in some migraine sufferers. Further studies are still needed to clarify if migraine is associated with unidentified mutations on the mtDNA or on nuclear genes that code mitochondrial proteins. In this paper, we review morphological, biochemical, imaging and genetic studies which bear on the hypothesis that migraine may be related to mitochondrial dysfunction at least in some individuals. ᮀ Brain oxidative metabolism, magnetic resonance spectroscopy, migraine, mitochondrial dysfunction, mutation
Journal of the Neurological Sciences, 2009
Friedreich's ataxia (FRDA) is an autosomal recessive disorder caused by mutations in the gene enc... more Friedreich's ataxia (FRDA) is an autosomal recessive disorder caused by mutations in the gene encoding frataxin, a mitochondrial protein implicated in iron metabolism. Current evidence suggests that loss of frataxin causes iron overload in tissues, and increase in free-radical production leading to oxidation and inactivation of mitochondrial respiratory chain enzymes, particularly Complexes I, II, III and aconitase. Glutathione plays an important role in the detoxification of ROS in the Central Nervous System (CNS), where it also provides regulation of protein function by glutathionylation. The cytoskeletal proteins are particularly susceptible to oxidation and appear constitutively glutathionylated in the human CNS. Previously, we showed loss of cytoskeletal organization in fibroblasts of patients with FRDA found to be associated with increased levels of glutathione bound to cytoskeletal proteins. In this study, we analysed the glutathionylation of proteins in the spinal cord of patients with FRDA and the distribution of tubulin and neurofilaments in the same area. We found, for the first time, a significant rise of the dynamic pool of tubulin as well as abnormal distribution of the phosphorylated forms of human neurofilaments in FRDA motor neurons. In the same cells, the cytoskeletal abnormalities co-localized with an increase in protein glutathionylation and the mitochondrial proteins were normally expressed by immunocytochemistry. Our results suggest that in FRDA oxidative stress causes abnormally increased protein glutathionylation leading to prominent abnormalities of the neuronal cytoskeleton.
Electroencephalographic features of HIV+ and AIDS patients with no neurological and cognitive impairment
Electroencephalography and Clinical Neurophysiology, 1997
Effects of phophatidilserine on P300 event-related potential parameters and EEG map in patients with cognitive disorders
Electroencephalography and Clinical Neurophysiology, 1993
Cephalalgia, 2006
The molecular basis of migraine is still not completely understood. An impairment of mitochondria... more The molecular basis of migraine is still not completely understood. An impairment of mitochondrial oxidative metabolism might play a role in the pathophysiology of this disease, by influencing neuronal information processing. Biochemical assays of platelets and muscle biopsies performed in migraine sufferers have shown a decreased activity of the respiratory chain enzymes. Studies with phosphorus magnetic resonance spectroscopy ( 31 P-MRS) have demonstrated an impairment of the brain oxidative energy metabolism both during and between migraine attacks. However, molecular genetic studies have not detected specific mitochondrial DNA (mtDNA) mutations in patients with migraine, although other studies suggest that particular genetic markers (i.e. neutral polymorphisms or secondary mtDNA mutations) might be present in some migraine sufferers. Further studies are still needed to clarify if migraine is associated with unidentified mutations on the mtDNA or on nuclear genes that code mitochondrial proteins. In this paper, we review morphological, biochemical, imaging and genetic studies which bear on the hypothesis that migraine may be related to mitochondrial dysfunction at least in some individuals. ᮀ Brain oxidative metabolism, magnetic resonance spectroscopy, migraine, mitochondrial dysfunction, mutation
Naratriptan in the Preventive Treatment of Refractory Chronic Migraine: A Review of 27 Cases
Headache the Journal of Head and Face Pain, May 1, 2003
To review the efficacy of naratriptan as preventive treatment in 27 patients with chronic migrain... more To review the efficacy of naratriptan as preventive treatment in 27 patients with chronic migraine refractory to other commonly used preventive therapies. The treatment of chronic migraine often poses a major challenge to the clinician. Even when given expert care, patients with chronic migraine may continue to have daily or near-daily headaches. Clinical records and headache calendars were reviewed of 27 patients fulfilling the following inclusion criteria: (1) aged 18 to 65 years; (2) diagnosis of chronic migraine (formerly transformed migraine), according to the criteria proposed by Silberstein et al; (3) previous failure of at least 4 preventive medications prescribed as part of a management program that included nonpharmacological measures, preventive medication, acute care medication, and detoxification from overused medication; and (4) have used daily naratriptan for no less than 2 consecutive months. The dose of naratriptan prescribed was 2.5 mg twice daily. We considered the following outcomes: (1) frequency of headache, (2) intensity of pain, (3) number of days per month with severe headache, (4) headache index (frequency times intensity), and (5) proportion of patients who reverted to an episodic pattern of pain after 6 months of treatment. There was a statistically significant reduction in the frequency of headache days 2 months (15.3 days versus 24.1 days at baseline, P<.001), 6 months (9.1 days, P<.001), and 1 year (7.3 days, P<.001) after daily treatment with naratriptan was initiated. There was also a statistically significant reduction in the number of days per month of severe pain at 1 month (5.6 days versus 12.5 days at baseline, P<.01), 2 months (5.7 days, P<.01), 6 months (2.8 days, P<.01), and 1 year (2.6 days, P<.01). Similarly, there was a statistically significant reduction in the headache index at 2 months (33 versus 56.4 at baseline, P<.001), 6 months (19.5, P<.001), and 1 year (17.2, P<.001). Of the 20 patients who continued to use naratriptan daily for at least 6 months, 13 (65%) reverted to an episodic pattern of pain (migraine). At 1 year, 11 (55%) still continued to experience episodic headache, 1 (5%) relapsed to chronic migraine, and 2 (10%) were lost to follow-up. No patients had intolerability to naratriptan during the treatment period, and no one stopped treatment due to adverse events. Naratriptan may have a role in the preventive treatment of intractable chronic migraine. Prospective, controlled studies should be considered.
An Otorrinolaringol Ibero Am
Journal of the Neurological Sciences, Sep 1, 2009
Friedreich's ataxia (FRDA) is an autosomal recessive disorder caused by mutations in the gene enc... more Friedreich's ataxia (FRDA) is an autosomal recessive disorder caused by mutations in the gene encoding frataxin, a mitochondrial protein implicated in iron metabolism. Current evidence suggests that loss of frataxin causes iron overload in tissues, and increase in free-radical production leading to oxidation and inactivation of mitochondrial respiratory chain enzymes, particularly Complexes I, II, III and aconitase. Glutathione plays an important role in the detoxification of ROS in the Central Nervous System (CNS), where it also provides regulation of protein function by glutathionylation. The cytoskeletal proteins are particularly susceptible to oxidation and appear constitutively glutathionylated in the human CNS. Previously, we showed loss of cytoskeletal organization in fibroblasts of patients with FRDA found to be associated with increased levels of glutathione bound to cytoskeletal proteins. In this study, we analysed the glutathionylation of proteins in the spinal cord of patients with FRDA and the distribution of tubulin and neurofilaments in the same area. We found, for the first time, a significant rise of the dynamic pool of tubulin as well as abnormal distribution of the phosphorylated forms of human neurofilaments in FRDA motor neurons. In the same cells, the cytoskeletal abnormalities co-localized with an increase in protein glutathionylation and the mitochondrial proteins were normally expressed by immunocytochemistry. Our results suggest that in FRDA oxidative stress causes abnormally increased protein glutathionylation leading to prominent abnormalities of the neuronal cytoskeleton.
Headaches of rhinogenic origin illustrate an interesting paradox. Little is known about their pat... more Headaches of rhinogenic origin illustrate an interesting paradox. Little is known about their pathophysiology, mechanisms, and prevalence; yet, the concept that these headaches are of importance is widely accepted. This article discusses the relationship between fronto-turbinalis sinus expansion and headaches, as well as headache outcomes after surgical approach.
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Papers by Michele Feleppa