Roberto Simone - Academia.edu (original) (raw)

Papers by Roberto Simone

Research paper thumbnail of Gian Camillo ManzoniVincenzo BonavitaGennaro BussonePietro Cortelli • Maria Carola NarboneSabina CevoliDomenico D'AmicoRoberto De Simone • Paola TorelliOn behalf of ANIRCEF (Associazione Neurologica Italiana Ricerca Cefalee)

Research paper thumbnail of Primary stabbing headache: A new dural sinus stenosis-associated primary headache?

Journal of the Neurological Sciences, Oct 1, 2013

Research paper thumbnail of Brainstem activation in cluster headache: An adaptive behavioural response?

Cephalalgia, 2013

Introduction The functional neuroimaging of headache patients has revolutionized our understandin... more Introduction The functional neuroimaging of headache patients has revolutionized our understanding of the pathophysiology of primary headaches, providing unique insights into these syndromes. Indeed, functional neuroimaging studies have shown the activation of specific brain structures, the brainstem in migraine and posterior hypothalamus in cluster headache (CH), as well as in other trigeminal autonomic cephalalgias. We describe the functional neuroimaging findings in a patient suffering from CH headache, investigated with functional magnetic resonance imaging (fMRI) during typical pain attacks. Material and methods Two typical, consecutive CH attacks were investigated by two fMRI imaging sessions on the same day. Both fMRI scans were performed at rest, during the CH attacks and the pain-free state induced by subcutaneous administration of sumatriptan. Results Significant activation of the bilateral red nucleus, ventral pons and trigeminal root entry zone ipsilaterally to the pain ...

Research paper thumbnail of Multiple cranial neuropathy due to varicella zoster virus reactivation without vesicular rash: a challenging diagnosis

Neurological Sciences, May 9, 2023

Research paper thumbnail of Idiopathic Intracranial Hypertension Without Papilledema

Archives of Neurology, 1991

Research paper thumbnail of A clinical comparison of trigeminal neuralgic pain in patients with and without underlying multiple sclerosis

Neurological Sciences, 2005

Despite clinical similitude, there is a tendency to consider trigeminal pain in multiple sclerosi... more Despite clinical similitude, there is a tendency to consider trigeminal pain in multiple sclerosis (MS) as a distinct condition. To evaluate clinical differences in trigeminal pain presentation in patients with and without underlying MS, we compared clinical characteristics of facial pain found in 15 consecutive MS patients with those reported by 13 consecutive subjects diagnosed with classical trigeminal neuralgia. The only significant difference between MS and non-MS neuralgic patients was the age of onset of pain (43.4±10.5 in MS vs. 59.6±11.50 in non-MS patients, p=0.000629, unpaired Student's t-test). No differences were observed for side, duration and quality of pain, trigeminal branches involved, presence of trigger areas or factors, pain refractive period, remitting-relapsing or chronic course. There was only a trend without statistical significance in interval pain and trigeminal hypoesthesia, more frequent in MS population. Only one patient in the MS group presented with long-lasting episodes (45-60 min) of atypical odontalgia. Our findings support the view of a common pathogenetic mechanism underlying TN in the two groups, possibly related to demyelination of the trigeminal entry root in the pons. Typical TN in MS patients should be considered as "symptomatic trigeminal neuralgia".

Research paper thumbnail of Towards a definition of comorbidity in the light of clinical complexity

Neurological Sciences, 2008

Clinical complexity encompasses multiple levels, including all the disorders and conditions exper... more Clinical complexity encompasses multiple levels, including all the disorders and conditions experienced by a person along cross-sectional and longitudinal contexts, the diversity of severity levels and courses of clinical conditions, but also the plurality of values of people experiencing health problems and seeking help for them. The term comorbidity refers to the association of two distinct diseases in the same individual at a rate higher than expected by chance. Looking systematically to comorbidity represents the main road to approach patients' clinical complexity. Once epidemiologically established through population or community surveys, the study of the comorbidity direction and of the chronological patterns of associated clinical entities may offer relevant information from both a clinical and a scientific point of view. Comorbidity profiles of migraine and tension-type headache offer a paradigmatic example to appraise and highlight headache patient clinical complexity, allowing the conversion of diagnosis from a validated cluster of symptoms to a person-centred clinical diagnosis.

Research paper thumbnail of Pain as an evolutionary necessity

Neurological Sciences, 2011

The proposed title &a... more The proposed title "Pain as an evolutionary necessity" could lead to a broad debate with implications covering many chapters of the medicine and particularly of clinical neurology. In the present perspective, the discussion will focus on migraine and cluster headache chosen as elective examples of biological and not only clinical conditions, that unveil the bond between pain and necessity. Migraine, cluster headache, and perhaps other primary headaches begin to be depicted in terms of recurrent activation of innate bio-behavioral specific patterns, with a crucial and highly conserved evolutionarily adaptive significance. The pan-mammalian sickness behavior and the fight or flight response, selectively activated by different kinds of pain, are here proposed as paradigmatic of migraine and cluster headache attacks associated behaviors, allowing to reformulate these forms as the inappropriate recurrent presentation of coordinated allostatic processes, modeled along million of years of natural evolution. In this light, all the multifaceted characteristics of migraine and cluster headache attacks can be reinterpreted as complex and integrated allostatic defensive reactions to an inescapable or to an escapable pain, respectively aimed to the restoration of biologic homeostasis through a temporary disengagement from active interaction with environment (migraine associated sickness behavior) or, on the contrary, to promote the coordinated biological changes preparatory to emergency and defensive behaviors (cluster headache-related fight or flight response).

Research paper thumbnail of Molecular Analysis of Cluster Headache

The Clinical Journal of Pain, 2015

Objectives: Cluster headache (CH) is characterized by severe, recurrent, unilateral attacks of ex... more Objectives: Cluster headache (CH) is characterized by severe, recurrent, unilateral attacks of extreme intensity and brief duration. Variants in a myriad of genes were studied in sporadic CH patients, often with conflicting results. Methods: We studied gene mutations in some candidate genes, hypocretin receptor 2, Clock, and alcohol dehydrogenase 4 (ADH4), in 54 unrelated sporadic CH patients and in 200 controls in 8 kindreds/families that included more affected and nonaffected cases. Furthermore, we performed the whole-genome scanning by comparative genomic hybridization, searching for rearrangements associated with DNA gain or loss in a subset of sporadic and familial CH and control participants. Results: The analysis of candidate genes revealed that only allele and genotype frequency of the 2 ADH4 mutations resulted significantly between sporadic CH and controls; the same mutations were homozygous in CH patients from 2 families. The comparative genomic hybridization analysis revealed 2 novel rearrangements that involved the intron regions of thyrotropin-releasing hormone-degrading enzyme and neurexin 3 (NRXN3) genes, respectively. The first arrangement was present either in CH or in controls, whereas the second one was specifically found in some sporadic and familial CH cases. Conclusions: Our data (although obtained on a small number of cases) confirm the genetic heterogeneity of CH, suggesting that mutations in the ADH4 gene and a novel rearrangement involving NRXN3 gene might be related to CH in a subset of cases.

Research paper thumbnail of Recurrent reflex syncope in idiopathic intracranial hypertension patient resolved after lumbar puncture: pathogenetic implications

BMC Neurology

Background Idiopathic intracranial hypertension is a disease characterized by increased intracran... more Background Idiopathic intracranial hypertension is a disease characterized by increased intracranial cerebrospinal fluid volume and pressure without evidence of other intracranial pathology. Dural sinuses are rigid structures representing a privileged low-pressure intracranial compartment. Rigidity of dural sinus ensures that the large physiologic fluctuations of cerebrospinal fluid pressure associated with postural changes or to Valsalva effect cannot be transmitted to the sinus. An abnormal dural sinus collapsibility, especially when associated with various anatomical sinus narrowing, has been proposed as a key factor in the pathogenesis of idiopathic intracranial hypertension. This pathogenetic model is based on an excessive collapsibility of the dural sinuses that leads to the triggering of a self-limiting venous collapse positive feedback-loop between the cerebrospinal fluid pressure, that compresses the sinus, and the increased dural sinus pressure upstream, that reduces the c...

Research paper thumbnail of Clinical features, disease progression, and use of healthcare resources in a large sample of 866 patients from 24 headache centers: A real‐life perspective from the Italian chROnic migraiNe (IRON) project

Headache: The Journal of Head and Face Pain, 2021

To develop a dedicated Italian chronic migraine (CM) database (IRON project) to overcome disease ... more To develop a dedicated Italian chronic migraine (CM) database (IRON project) to overcome disease misconceptions, improve clinical administration, reduce patients’ burden, and rationalize economic resource allotment.

Research paper thumbnail of Dural sinus collapsibility, idiopathic intracranial hypertension, and the pathogenesis of chronic migraine

Neurological Sciences, 2019

Available evidences suggest that a number of known assumption on idiopathic intracranial hyperten... more Available evidences suggest that a number of known assumption on idiopathic intracranial hypertension (IIH) with or without papilledema might be discussed. These include (1) the primary pathogenetic role of an excessive dural sinus collapsibility in IIH, allowing a new relatively stable intracranial fluids pressure balance at higher values; (2) the non-mandatory role of papilledema for a definite diagnosis; (3) the possibly much higher prevalence of IIH without papilledema than currently considered; (4) the crucial role of the cerebral compliance exhaustion that precede the raise in intracranial pressure and that may already be pathologic in cases showing a moderately elevated opening pressure; (5) the role as Bintracranial pressure sensor^played by the trigeminovascular innervation of dural sinuses and cortical bridge veins, which could represent a major source of CGRP and may explain the high comorbidity and the emerging causative link between IIHWOP and chronic migraine (CM). Accordingly, the control of intracranial pressure is to be considered a promising new therapeutic target in CM.

Research paper thumbnail of Pain cognition in migraine: from basic neurophysiology to a behavioral paradigm

Neurological Sciences, 2018

Most of the data in this review have been already reported by the authors in Neurological Science... more Most of the data in this review have been already reported by the authors in Neurological Science, but the goal of the present paper is to realize an integrated lecture of all the available data and look to the last achievements in pain cognition, with a special focus on migraine and chronic migraine. According to the proposed integrated perspective, migraine can be viewed as an adaptive behavioral response with evolutionistic advantages.

Research paper thumbnail of Efficacy-Safety Rate of Low Doses of Flunarizine in Childhood Migraine Treatment

Cephalalgia, 1989

Although flunarizine has been found effective in the treatment of migraine, its safety has recent... more Although flunarizine has been found effective in the treatment of migraine, its safety has recently come under attack because of reported side effects which suggest an interaction with central dopamine transmission. In particular, extrapiramidal and depressive disturbances have been found in a significant number of patient! >50 years during prolonged treatment with flunarizine at daily doses of at least 10 mg. In a prvious study(1) we found no incidence of extrapiramidal or depressive disturbances in children suffering from migraine and

Research paper thumbnail of Efficacy of Flunarizine in the Prophylaxis of Migraine in Children: A Double Blind, Cross-Over, Controlled Study

Research paper thumbnail of Sudden re-opening of collapsed transverse sinuses and longstanding clinical remission after a single lumbar puncture in a case of idiopathic intracranial hypertension. Pathogenetic implications

Neurological Sciences, 2005

The aetiopathogenetic role of sinus venous obstructions carried by most idiopathic intracranial h... more The aetiopathogenetic role of sinus venous obstructions carried by most idiopathic intracranial hypertension (IIH) patients is controversial. We report the case of a young woman diagnosed with IIH with papilloedema and narrowing of transverse sinuses, in which lowering of intracranial pressure by a single 20 ml cerebrospinal fluid (CSF) resulted in a strong dimensional increase of the transverse sinuses. Changes were followed by clinical remission and normalisation of optical nerve calibre, maintained after a 2-month follow-up. Our findings indicate that, although secondary to CSF hypertension, venous sinuses compression may have an important role in hypertensive status maintenance. Pathogenetic implications of venous sinus compression by hypertensive CSF in IIH are discussed.

Research paper thumbnail of Commentary: Idiopathic Intracranial Hypertension Without Papilledema (IIHWOP) in Chronic Refractory Headache

Frontiers in Neurology, 2019

Research paper thumbnail of Letter to the Editor. The causative role of sinus stenosis in idiopathic intracranial hypertension

Journal of Neurosurgery, 2018

JS: Contribution of combined intraoperative electrophysiological investigation with 3-T intraoper... more JS: Contribution of combined intraoperative electrophysiological investigation with 3-T intraoperative MRI for awake cerebral glioma surgery: comprehensive review of the clinical implications and radiological outcomes. Neurosurg Focus 40(3):E14,

Research paper thumbnail of Endolymphatic hydrops in idiopathic intracranial hypertension: prevalence and clinical outcome after lumbar puncture. Preliminary data

Neurological Sciences, 2017

Idiopathic intracranial hypertension is characterized by raised intracranial pressure (ICP) witho... more Idiopathic intracranial hypertension is characterized by raised intracranial pressure (ICP) without any underlying pathology, presenting with (IIH) or without papilledema (IIHWOP). Headache, often on daily basis, is the most frequent symptom. Among audiovestibular symptoms, tinnitus and dizziness are commonly reported, while vertigo and hearing impairment are infrequent reports. Endolymphatic hydrops (ELH) is the typical histopathologic feature of Ménière disease, a condition featured by episodes of vertigo, dizziness, fluctuating hearing loss, tinnitus, and aural fullness. Evidences suggest that ICP is transmitted to inner ear. The aim of this study is to investigate the prevalence of ELH symptoms in IIH/ IIHWOP and the relationship between the raised ICP and ELH. The prevalence of chronic headache and of ELH symptoms was investigated in a consecutive series of IIH/ IIHWOP patients, and a standard audiometry with hearing threshold measurement (pure-tone average-PTA) was performed. Differences in chronic headache and ELH symptoms prevalence and changes of PTA threshold were calculated after ICP normalization by lumbar puncture (LP). Thirty-one patients (17 with IIH and 14 with IIH-WOP) were included. Before LP, chronic headache was present in 93.5%. The percentages of patients reporting tinnitus, dizziness, vertigo, and aural fullness were 67.7, 77.4, 22.6, and 61.3%, respectively. Headache frequency as well as ELH symptoms and PTA significantly improved after LP. The improvement of PTA and of ELH symptoms observed after LP in this series of IIH/IIHWOP patients indicates that a raised ICP, a condition known to be involved in the progression and refractoriness of migraine pain, has also a role in ELH. We propose that intracranial hypertension may represent the shared pathogenetic step explaining the large epidemiological comorbidity between migraine and vestibular symptoms, at present conceptualized as ''vestibular migraine.'' Keywords Raised intracranial pressure Á Idiopathic intracranial hypertension Á Endolymphatic hydrops Á Vestibular migraine Á Ménière disease

Research paper thumbnail of The role of dural sinus stenosis in idiopathic intracranial hypertension pathogenesis: the self-limiting venous collapse feedback-loop model

Panminerva medica, 2014

In recent years the efficacy of endovascular venous stenting in idiopathic IIH treatment has been... more In recent years the efficacy of endovascular venous stenting in idiopathic IIH treatment has been consistently reported, strongly suggesting that sinus stenosis should be viewed as a causative factor rather than a secondary phenomenon. We propose that in subjects carrying one or more collapsible segments of large cerebral venous collectors and exposed to a number of different promoting factors, sinus venous compression and cerebrospinal fluid (CSF) hypertension may influence each other in a circular way, leading to a new relatively stable venous/CSF pressures balance state at higher values. The mechanism relay on self-limiting venous collapse (SVC) feedback-loop between the CSF pressure, that compresses the sinus, and the consequent venous pressure rise, that increases the CSF pressure. The result is the "coupled" increase of both pressure values, a phenomenon not expected in presence of sufficiently rigid central veins. Once the maximum stretch of venous wall is reached t...

Research paper thumbnail of Gian Camillo ManzoniVincenzo BonavitaGennaro BussonePietro Cortelli • Maria Carola NarboneSabina CevoliDomenico D'AmicoRoberto De Simone • Paola TorelliOn behalf of ANIRCEF (Associazione Neurologica Italiana Ricerca Cefalee)

Research paper thumbnail of Primary stabbing headache: A new dural sinus stenosis-associated primary headache?

Journal of the Neurological Sciences, Oct 1, 2013

Research paper thumbnail of Brainstem activation in cluster headache: An adaptive behavioural response?

Cephalalgia, 2013

Introduction The functional neuroimaging of headache patients has revolutionized our understandin... more Introduction The functional neuroimaging of headache patients has revolutionized our understanding of the pathophysiology of primary headaches, providing unique insights into these syndromes. Indeed, functional neuroimaging studies have shown the activation of specific brain structures, the brainstem in migraine and posterior hypothalamus in cluster headache (CH), as well as in other trigeminal autonomic cephalalgias. We describe the functional neuroimaging findings in a patient suffering from CH headache, investigated with functional magnetic resonance imaging (fMRI) during typical pain attacks. Material and methods Two typical, consecutive CH attacks were investigated by two fMRI imaging sessions on the same day. Both fMRI scans were performed at rest, during the CH attacks and the pain-free state induced by subcutaneous administration of sumatriptan. Results Significant activation of the bilateral red nucleus, ventral pons and trigeminal root entry zone ipsilaterally to the pain ...

Research paper thumbnail of Multiple cranial neuropathy due to varicella zoster virus reactivation without vesicular rash: a challenging diagnosis

Neurological Sciences, May 9, 2023

Research paper thumbnail of Idiopathic Intracranial Hypertension Without Papilledema

Archives of Neurology, 1991

Research paper thumbnail of A clinical comparison of trigeminal neuralgic pain in patients with and without underlying multiple sclerosis

Neurological Sciences, 2005

Despite clinical similitude, there is a tendency to consider trigeminal pain in multiple sclerosi... more Despite clinical similitude, there is a tendency to consider trigeminal pain in multiple sclerosis (MS) as a distinct condition. To evaluate clinical differences in trigeminal pain presentation in patients with and without underlying MS, we compared clinical characteristics of facial pain found in 15 consecutive MS patients with those reported by 13 consecutive subjects diagnosed with classical trigeminal neuralgia. The only significant difference between MS and non-MS neuralgic patients was the age of onset of pain (43.4±10.5 in MS vs. 59.6±11.50 in non-MS patients, p=0.000629, unpaired Student's t-test). No differences were observed for side, duration and quality of pain, trigeminal branches involved, presence of trigger areas or factors, pain refractive period, remitting-relapsing or chronic course. There was only a trend without statistical significance in interval pain and trigeminal hypoesthesia, more frequent in MS population. Only one patient in the MS group presented with long-lasting episodes (45-60 min) of atypical odontalgia. Our findings support the view of a common pathogenetic mechanism underlying TN in the two groups, possibly related to demyelination of the trigeminal entry root in the pons. Typical TN in MS patients should be considered as "symptomatic trigeminal neuralgia".

Research paper thumbnail of Towards a definition of comorbidity in the light of clinical complexity

Neurological Sciences, 2008

Clinical complexity encompasses multiple levels, including all the disorders and conditions exper... more Clinical complexity encompasses multiple levels, including all the disorders and conditions experienced by a person along cross-sectional and longitudinal contexts, the diversity of severity levels and courses of clinical conditions, but also the plurality of values of people experiencing health problems and seeking help for them. The term comorbidity refers to the association of two distinct diseases in the same individual at a rate higher than expected by chance. Looking systematically to comorbidity represents the main road to approach patients' clinical complexity. Once epidemiologically established through population or community surveys, the study of the comorbidity direction and of the chronological patterns of associated clinical entities may offer relevant information from both a clinical and a scientific point of view. Comorbidity profiles of migraine and tension-type headache offer a paradigmatic example to appraise and highlight headache patient clinical complexity, allowing the conversion of diagnosis from a validated cluster of symptoms to a person-centred clinical diagnosis.

Research paper thumbnail of Pain as an evolutionary necessity

Neurological Sciences, 2011

The proposed title &a... more The proposed title "Pain as an evolutionary necessity" could lead to a broad debate with implications covering many chapters of the medicine and particularly of clinical neurology. In the present perspective, the discussion will focus on migraine and cluster headache chosen as elective examples of biological and not only clinical conditions, that unveil the bond between pain and necessity. Migraine, cluster headache, and perhaps other primary headaches begin to be depicted in terms of recurrent activation of innate bio-behavioral specific patterns, with a crucial and highly conserved evolutionarily adaptive significance. The pan-mammalian sickness behavior and the fight or flight response, selectively activated by different kinds of pain, are here proposed as paradigmatic of migraine and cluster headache attacks associated behaviors, allowing to reformulate these forms as the inappropriate recurrent presentation of coordinated allostatic processes, modeled along million of years of natural evolution. In this light, all the multifaceted characteristics of migraine and cluster headache attacks can be reinterpreted as complex and integrated allostatic defensive reactions to an inescapable or to an escapable pain, respectively aimed to the restoration of biologic homeostasis through a temporary disengagement from active interaction with environment (migraine associated sickness behavior) or, on the contrary, to promote the coordinated biological changes preparatory to emergency and defensive behaviors (cluster headache-related fight or flight response).

Research paper thumbnail of Molecular Analysis of Cluster Headache

The Clinical Journal of Pain, 2015

Objectives: Cluster headache (CH) is characterized by severe, recurrent, unilateral attacks of ex... more Objectives: Cluster headache (CH) is characterized by severe, recurrent, unilateral attacks of extreme intensity and brief duration. Variants in a myriad of genes were studied in sporadic CH patients, often with conflicting results. Methods: We studied gene mutations in some candidate genes, hypocretin receptor 2, Clock, and alcohol dehydrogenase 4 (ADH4), in 54 unrelated sporadic CH patients and in 200 controls in 8 kindreds/families that included more affected and nonaffected cases. Furthermore, we performed the whole-genome scanning by comparative genomic hybridization, searching for rearrangements associated with DNA gain or loss in a subset of sporadic and familial CH and control participants. Results: The analysis of candidate genes revealed that only allele and genotype frequency of the 2 ADH4 mutations resulted significantly between sporadic CH and controls; the same mutations were homozygous in CH patients from 2 families. The comparative genomic hybridization analysis revealed 2 novel rearrangements that involved the intron regions of thyrotropin-releasing hormone-degrading enzyme and neurexin 3 (NRXN3) genes, respectively. The first arrangement was present either in CH or in controls, whereas the second one was specifically found in some sporadic and familial CH cases. Conclusions: Our data (although obtained on a small number of cases) confirm the genetic heterogeneity of CH, suggesting that mutations in the ADH4 gene and a novel rearrangement involving NRXN3 gene might be related to CH in a subset of cases.

Research paper thumbnail of Recurrent reflex syncope in idiopathic intracranial hypertension patient resolved after lumbar puncture: pathogenetic implications

BMC Neurology

Background Idiopathic intracranial hypertension is a disease characterized by increased intracran... more Background Idiopathic intracranial hypertension is a disease characterized by increased intracranial cerebrospinal fluid volume and pressure without evidence of other intracranial pathology. Dural sinuses are rigid structures representing a privileged low-pressure intracranial compartment. Rigidity of dural sinus ensures that the large physiologic fluctuations of cerebrospinal fluid pressure associated with postural changes or to Valsalva effect cannot be transmitted to the sinus. An abnormal dural sinus collapsibility, especially when associated with various anatomical sinus narrowing, has been proposed as a key factor in the pathogenesis of idiopathic intracranial hypertension. This pathogenetic model is based on an excessive collapsibility of the dural sinuses that leads to the triggering of a self-limiting venous collapse positive feedback-loop between the cerebrospinal fluid pressure, that compresses the sinus, and the increased dural sinus pressure upstream, that reduces the c...

Research paper thumbnail of Clinical features, disease progression, and use of healthcare resources in a large sample of 866 patients from 24 headache centers: A real‐life perspective from the Italian chROnic migraiNe (IRON) project

Headache: The Journal of Head and Face Pain, 2021

To develop a dedicated Italian chronic migraine (CM) database (IRON project) to overcome disease ... more To develop a dedicated Italian chronic migraine (CM) database (IRON project) to overcome disease misconceptions, improve clinical administration, reduce patients’ burden, and rationalize economic resource allotment.

Research paper thumbnail of Dural sinus collapsibility, idiopathic intracranial hypertension, and the pathogenesis of chronic migraine

Neurological Sciences, 2019

Available evidences suggest that a number of known assumption on idiopathic intracranial hyperten... more Available evidences suggest that a number of known assumption on idiopathic intracranial hypertension (IIH) with or without papilledema might be discussed. These include (1) the primary pathogenetic role of an excessive dural sinus collapsibility in IIH, allowing a new relatively stable intracranial fluids pressure balance at higher values; (2) the non-mandatory role of papilledema for a definite diagnosis; (3) the possibly much higher prevalence of IIH without papilledema than currently considered; (4) the crucial role of the cerebral compliance exhaustion that precede the raise in intracranial pressure and that may already be pathologic in cases showing a moderately elevated opening pressure; (5) the role as Bintracranial pressure sensor^played by the trigeminovascular innervation of dural sinuses and cortical bridge veins, which could represent a major source of CGRP and may explain the high comorbidity and the emerging causative link between IIHWOP and chronic migraine (CM). Accordingly, the control of intracranial pressure is to be considered a promising new therapeutic target in CM.

Research paper thumbnail of Pain cognition in migraine: from basic neurophysiology to a behavioral paradigm

Neurological Sciences, 2018

Most of the data in this review have been already reported by the authors in Neurological Science... more Most of the data in this review have been already reported by the authors in Neurological Science, but the goal of the present paper is to realize an integrated lecture of all the available data and look to the last achievements in pain cognition, with a special focus on migraine and chronic migraine. According to the proposed integrated perspective, migraine can be viewed as an adaptive behavioral response with evolutionistic advantages.

Research paper thumbnail of Efficacy-Safety Rate of Low Doses of Flunarizine in Childhood Migraine Treatment

Cephalalgia, 1989

Although flunarizine has been found effective in the treatment of migraine, its safety has recent... more Although flunarizine has been found effective in the treatment of migraine, its safety has recently come under attack because of reported side effects which suggest an interaction with central dopamine transmission. In particular, extrapiramidal and depressive disturbances have been found in a significant number of patient! >50 years during prolonged treatment with flunarizine at daily doses of at least 10 mg. In a prvious study(1) we found no incidence of extrapiramidal or depressive disturbances in children suffering from migraine and

Research paper thumbnail of Efficacy of Flunarizine in the Prophylaxis of Migraine in Children: A Double Blind, Cross-Over, Controlled Study

Research paper thumbnail of Sudden re-opening of collapsed transverse sinuses and longstanding clinical remission after a single lumbar puncture in a case of idiopathic intracranial hypertension. Pathogenetic implications

Neurological Sciences, 2005

The aetiopathogenetic role of sinus venous obstructions carried by most idiopathic intracranial h... more The aetiopathogenetic role of sinus venous obstructions carried by most idiopathic intracranial hypertension (IIH) patients is controversial. We report the case of a young woman diagnosed with IIH with papilloedema and narrowing of transverse sinuses, in which lowering of intracranial pressure by a single 20 ml cerebrospinal fluid (CSF) resulted in a strong dimensional increase of the transverse sinuses. Changes were followed by clinical remission and normalisation of optical nerve calibre, maintained after a 2-month follow-up. Our findings indicate that, although secondary to CSF hypertension, venous sinuses compression may have an important role in hypertensive status maintenance. Pathogenetic implications of venous sinus compression by hypertensive CSF in IIH are discussed.

Research paper thumbnail of Commentary: Idiopathic Intracranial Hypertension Without Papilledema (IIHWOP) in Chronic Refractory Headache

Frontiers in Neurology, 2019

Research paper thumbnail of Letter to the Editor. The causative role of sinus stenosis in idiopathic intracranial hypertension

Journal of Neurosurgery, 2018

JS: Contribution of combined intraoperative electrophysiological investigation with 3-T intraoper... more JS: Contribution of combined intraoperative electrophysiological investigation with 3-T intraoperative MRI for awake cerebral glioma surgery: comprehensive review of the clinical implications and radiological outcomes. Neurosurg Focus 40(3):E14,

Research paper thumbnail of Endolymphatic hydrops in idiopathic intracranial hypertension: prevalence and clinical outcome after lumbar puncture. Preliminary data

Neurological Sciences, 2017

Idiopathic intracranial hypertension is characterized by raised intracranial pressure (ICP) witho... more Idiopathic intracranial hypertension is characterized by raised intracranial pressure (ICP) without any underlying pathology, presenting with (IIH) or without papilledema (IIHWOP). Headache, often on daily basis, is the most frequent symptom. Among audiovestibular symptoms, tinnitus and dizziness are commonly reported, while vertigo and hearing impairment are infrequent reports. Endolymphatic hydrops (ELH) is the typical histopathologic feature of Ménière disease, a condition featured by episodes of vertigo, dizziness, fluctuating hearing loss, tinnitus, and aural fullness. Evidences suggest that ICP is transmitted to inner ear. The aim of this study is to investigate the prevalence of ELH symptoms in IIH/ IIHWOP and the relationship between the raised ICP and ELH. The prevalence of chronic headache and of ELH symptoms was investigated in a consecutive series of IIH/ IIHWOP patients, and a standard audiometry with hearing threshold measurement (pure-tone average-PTA) was performed. Differences in chronic headache and ELH symptoms prevalence and changes of PTA threshold were calculated after ICP normalization by lumbar puncture (LP). Thirty-one patients (17 with IIH and 14 with IIH-WOP) were included. Before LP, chronic headache was present in 93.5%. The percentages of patients reporting tinnitus, dizziness, vertigo, and aural fullness were 67.7, 77.4, 22.6, and 61.3%, respectively. Headache frequency as well as ELH symptoms and PTA significantly improved after LP. The improvement of PTA and of ELH symptoms observed after LP in this series of IIH/IIHWOP patients indicates that a raised ICP, a condition known to be involved in the progression and refractoriness of migraine pain, has also a role in ELH. We propose that intracranial hypertension may represent the shared pathogenetic step explaining the large epidemiological comorbidity between migraine and vestibular symptoms, at present conceptualized as ''vestibular migraine.'' Keywords Raised intracranial pressure Á Idiopathic intracranial hypertension Á Endolymphatic hydrops Á Vestibular migraine Á Ménière disease

Research paper thumbnail of The role of dural sinus stenosis in idiopathic intracranial hypertension pathogenesis: the self-limiting venous collapse feedback-loop model

Panminerva medica, 2014

In recent years the efficacy of endovascular venous stenting in idiopathic IIH treatment has been... more In recent years the efficacy of endovascular venous stenting in idiopathic IIH treatment has been consistently reported, strongly suggesting that sinus stenosis should be viewed as a causative factor rather than a secondary phenomenon. We propose that in subjects carrying one or more collapsible segments of large cerebral venous collectors and exposed to a number of different promoting factors, sinus venous compression and cerebrospinal fluid (CSF) hypertension may influence each other in a circular way, leading to a new relatively stable venous/CSF pressures balance state at higher values. The mechanism relay on self-limiting venous collapse (SVC) feedback-loop between the CSF pressure, that compresses the sinus, and the consequent venous pressure rise, that increases the CSF pressure. The result is the "coupled" increase of both pressure values, a phenomenon not expected in presence of sufficiently rigid central veins. Once the maximum stretch of venous wall is reached t...