Research Interests: Neurology, Neurosurgery, Medicine, Humans, Neuroradiology, and 14 moreFemale, Headache, Male, Nausea, Clinical Sciences, International Classification of Diseases, Adult, Pilot Projects, Phonophobia, Pseudotumor Cerebri, Neurosciences, Translation for Neurological Sciences, Neurological Sciences, and lumbar puncture
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Research Interests: Neurology, Neurosurgery, Lithium, Medicine, Humans, and 15 moreTrigeminal Neuralgia, Drug Resistance, Headache, Anesthesia, Clinical Sciences, Cluster Headache, Neurological, Trigeminal, Neurosciences, Serotonin antagonists, Translation for Neurological Sciences, Verapamil, Calcium Channel Blockers, Neurological Sciences, and Adrenal cortex hormones
Spontaneous intracranial hypotension (SIH) is a rare disabling condition whose main clinical manifestation is orthostatic headache. We analysed clinical characteristics in relation to time to resolution in 90 consecutive patients... more
Spontaneous intracranial hypotension (SIH) is a rare disabling condition whose main clinical manifestation is orthostatic headache. We analysed clinical characteristics in relation to time to resolution in 90 consecutive patients diagnosed with SIH at our centre between 1993 and 2006. After excluding 7 patients lost to follow-up, the remaining 83 cases were divided into four groups: Group A (53 cases) with progressively worsening orthostatic headache; Group B (3 cases) with severe acute-onset orthostatic headache; Group C (9 cases) with fluctuating non-continuous headache, of mild severity, that, in 33% of cases, did not worsen on standing; Group D (18 cases), 5 with a previous history of headache, 14 with orthostatic headache, and 10 with altered neurological examination. Complete symptoms and neuroradiological resolution occurred during follow-up in Groups A, B and D, but was longer in Group D probably in relation to more severe clinical picture with altered neurological examination. However, after a mean of 52 months (range 24-108), none of the nine Group C patients had MRI indicating complete resolution. The main characteristic of Group C related to incomplete resolution was delayed diagnosis. These preliminary findings suggest that early diagnosis of SIH correlates with better outcome, further suggesting that patients with a new headache that may worsen on standing or sitting should undergo MRI with contrast to expedite a possible SIH diagnosis, even if the pain is relatively mild.
Research Interests: Neurology, Magnetic Resonance Imaging, Adolescent, Medicine, Humans, and 15 moreNeuroradiology, Female, Headache, Male, Anesthesia, Clinical Sciences, Aged, Middle Aged, Adult, Prognosis, Intracranial Hypertension, Neurosciences, Neurological Sciences, Interviews as topic, and Neurological examination
... M Leone, D Dodick1, A Rigamonti, D D'Amico, L Grazzi, E Mea & G Bussone Carlo Besta National Neurological Institute, Milano, Italy, and 1Mayo Headache Center, Cerebrovascular Clinic, Mayo Clinic Scottsdale, Scottsdale AZ, USA... more
... M Leone, D Dodick1, A Rigamonti, D D'Amico, L Grazzi, E Mea & G Bussone Carlo Besta National Neurological Institute, Milano, Italy, and 1Mayo Headache Center, Cerebrovascular Clinic, Mayo Clinic Scottsdale, Scottsdale AZ, USA Massimo Leone, Carlo Besta National ...
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Alterations of the intracranial pressure (ICP) may be present in several conditions. The aim of this brief review is to focus on two relatively rare conditions characterized by alterations in cerebro-spinal fluid dynamics--Spontaneous... more
Alterations of the intracranial pressure (ICP) may be present in several conditions. The aim of this brief review is to focus on two relatively rare conditions characterized by alterations in cerebro-spinal fluid dynamics--Spontaneous Intracranial hypotension (SIH) and Idiopathic Intracranial hypertension (IIH)--in which headache is one of the key symptoms. The most relevant clinical features, the expected MRI findings, and the therapeutic options regarding both conditions are discussed.
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We examined 59 consecutive patients presenting between 1993 and 2006 at our centre diagnosed with headache associated with spontaneous intracranial hypotension syndrome (SIH). Thirty-six (61%) patients were women; the mean age was 47... more
We examined 59 consecutive patients presenting between 1993 and 2006 at our centre diagnosed with headache associated with spontaneous intracranial hypotension syndrome (SIH). Thirty-six (61%) patients were women; the mean age was 47 years (range 20-68). Cerebral MRI with contrast confirmed SIH in all patients. Headache characteristics were obtained by direct semistructured interview; in a minority of cases information was completed retrospectively through a phone call. All SIH patients suffered from headache. Early recognition of SIH may avoid dangerous worsening due to delayed diagnosis. Orthostatic headache, the main symptom, suggests the diagnosis.
Research Interests: Neurology, Magnetic Resonance Imaging, Medicine, Cerebrospinal Fluid, Brain, and 15 moreHumans, Neuroradiology, Female, Male, Clinical Sciences, Neurological, Aged, Middle Aged, Adult, Neurological Sciences, Intracranial Hypotension, Headache disorders, Migraine disorders, Dura mater, and Diagnostic errors
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Research Interests: Deep Brain Stimulation, Neuroimaging, Magnetic Resonance Imaging, Image Analysis, Mortality, and 15 moreMedicine, Human, Humans, Hypothalamus, Follow Up, Article, Clinical Sciences, Cluster Headache, Hypothesis, Adverse Event, Electrode, Electrostimulation, Gray Matter, Movement Disorder, and High Frequency Stimulation
To investigate the presence of Restless Legs Syndrome (RLS) in Cluster Headache (CH) patients compared to headache-free controls. Cross-sectional case-control study of CH patients presenting at tertiary headache centers over the period... more
To investigate the presence of Restless Legs Syndrome (RLS) in Cluster Headache (CH) patients compared to headache-free controls. Cross-sectional case-control study of CH patients presenting at tertiary headache centers over the period January-December 2008. Fifty consecutive patients (6 women and 44 men) of mean age of 39.7 year (standard deviation 10.9) with episodic or chronic CH diagnosed according to ICHD-II criteria and 50 headache-free subjects matched by age and sex were recruited. None of the CH patients had RLS. Six (12%) headache-free controls had RLS. Our data indicate no probable relationship between CH and RLS. However, since both conditions have a circadian rhythm and are associated with altered melatonin secretion, we conjecture that reduced nocturnal melatonin in CH likely allows sustained dopaminergic activity which could be protective against RLS in CH patients.
Research Interests: Pediatrics, Medicine, Dopamine, Melatonin, Humans, and 15 moreCircadian Rhythm, Female, Male, Clinical Sciences, Cluster Headache, Aged, Middle Aged, Adult, Restless Legs Syndrome, Observational Study, Cross Sectional Studies, Neurosciences, Case Control Studies, Restless Leg Syndrome, and dopaminergic
Cluster headache (CH) is a primary headache with excruciatingly painful attacks that are strictly unilateral. About 10% of cases experience no significant remission, and about 15% of these do not respond to medication, so surgery is... more
Cluster headache (CH) is a primary headache with excruciatingly painful attacks that are strictly unilateral. About 10% of cases experience no significant remission, and about 15% of these do not respond to medication, so surgery is considered. Neuroimaging studies show that the posterior inferior hypothalamus is activated during CH attacks and is plausibly the CH generator. We report on 16 chronic CH patients, with headaches refractory to all medication, who received long-term hypothalamic stimulation following electrode implant to the posterior inferior hypothalamus. After a mean follow-up of 23 months, a persistent pain-free to almost pain-free state was achieved in 13/16 patients (15/18 implants; 83.3%) a mean of 42 days (range 1-86 days) after monopolar stimulation initiation. Ten patients (11 implants) are completely pain-free. A common side effect was transient diplopia, which limited stimulation amplitude. In one patient, a small non-symptomatic haemorrhage into the 3rd ventricle occurred following implant, but regressed 24 h later. Persistent side effects are absent except in one patient with bilateral stimulation, in whom stimulation was stopped to resolve vertigo and worsened bradycardia, but was resumed later without further problems. Hypothalamic stimulation is an effective, safe and well tolerated treatment for chronic drug-refractory CH. It appears as a valid alternative to destructive surgical modalities, and has the additional advantage of being reversible.
Research Interests: Neurology, Deep Brain Stimulation, Treatment Outcome, Medicine, TIME, and 13 moreHumans, Anesthesia, Clinical Sciences, Cluster Headache, Implant, Stimulation, Time, Side Effect, Neurosciences, SECONDARY PREVENTION, Translation for Neurological Sciences, Neurological Sciences, and Postoperative Complications
In the last ten years pathophysiology of primary headaches has received new insights from neuroimaging studies. Positron emission tomography (PET) showed activation of specific brain structures, brainstem in migraine and hypothalamic grey... more
In the last ten years pathophysiology of primary headaches has received new insights from neuroimaging studies. Positron emission tomography (PET) showed activation of specific brain structures, brainstem in migraine and hypothalamic grey in trigeminal autonomic cephalalgias. This brain activation suggests it may intervene both in a permissive or triggering manner and as a response to pain driven by the first division of the trigeminal nerve. Voxel-based morphometry has suggested that there is a correlation between the brain area activated specifically in acute cluster headache - the posterior hypothalamic grey matter - and an increase in grey matter in the same region. New insights into mechanisms of head pain have emerged thanks to neuroimaging obtained in experimentally induced headaches, and during peripheral and central neurostimulation.
Research Interests: Neurology, Neuroimaging, Medicine, Brain, Humans, and 15 moreNeuroradiology, Hypothalamus, Brainstem, Migraine, Clinical Sciences, Cluster Headache, Neurological, Functional Neuroimaging, Brain Structure, Analgesics, Headaches, Brain stem, Neurological Sciences, Headache disorders, and Migraine disorders
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Long-term hypothalamic stimulation is effective in improving drug-resistant chronic cluster headache (CH). We assessed acute hypothalamic stimulation to resolve ongoing CH attacks in 16 patients implanted to prevent chronic CH,... more
Long-term hypothalamic stimulation is effective in improving drug-resistant chronic cluster headache (CH). We assessed acute hypothalamic stimulation to resolve ongoing CH attacks in 16 patients implanted to prevent chronic CH, investigating 136 attacks. A pain intensity reduction of > or =50% occurred in 25 of 108 evaluable attacks (23.1%). Acute hypothalamic stimulation is not effective in resolving ongoing CH attacks, suggesting that hypothalamic stimulation acts by complex mechanisms in CH prevention.
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In about 20% of chronic cluster headache (CH) cases, drugs may become ineffective. Under these circumstances, steroids and triptans are frequently employed leading to fearful side effects in one and high costs in the other. The direct... more
In about 20% of chronic cluster headache (CH) cases, drugs may become ineffective. Under these circumstances, steroids and triptans are frequently employed leading to fearful side effects in one and high costs in the other. The direct costs of drug-resistant chronic CH are mainly due to frequent medical consultations and frequent use of expensive drugs. In recent years, hypothalamic stimulation has been employed to treat drug-resistant chronic CH patients suffering multiple daily attacks and long-term results from different centres show a 60% overall benefit. Nine years since the introduction of this technique, we attempt a preliminary analysis of the direct costs of hypothalamic stimulation based on patients treated at our centre. We estimated the following direct costs as follows: cost of neurosurgery plus cost of equipment (electrode, connection and impulse generator = 25,000 euro), cost of hospital admissions in long-term follow-up (2,000 euro per admission), cost of single sumatriptan injection (25 euro). Number of daily sumatriptan injections in the year before and for each year after hypothalamic implantation was obtained from headache diaries. To estimate the saving due to the reduction in sumatriptan consumption following hypothalamic stimulation, we calculated the following for each year of follow-up after surgery: number of sumatriptan injections in the year before surgery minus number of sumatriptan injections in each year, updated to December 2008. In our 19 implanted patients, the costs of neurosurgery plus cost of equipment were 475,000 euro; the costs of hospital admissions during follow up were 250,000 euro. Reduction in sumatriptan consumption resulted in a total saving of 3,573,125 euro. Hence, in our 19 patients, the sumatriptan saving (3,573,125 euro) minus the direct costs due to operation and follow up hospitalisations (475,000 + 250,000) euro is equal to 2,848,125 euro. These preliminary results indicate that hypothalamic stimulation is associated with marked reduction of direct costs in the management of complete drug-resistant chronic CH.
Research Interests: Neurosurgery, Deep Brain Stimulation, Medicine, Humans, Hypothalamus, and 14 moreHospitalization, Female, Drug Resistance, Male, Anesthesia, Follow-up studies, Clinical Sciences, Cluster Headache, Adult, Medical Electronics, Health Care Costs, Neurosciences, Translation for Neurological Sciences, and Neurological Sciences
AIDA Cefalee is a database for the management of headache patients developed on behalf of the Italian Neurological Association for Headache Research (ANIRCEF). The system integrates a diagnostic expert system able to suggest the correct... more
AIDA Cefalee is a database for the management of headache patients developed on behalf of the Italian Neurological Association for Headache Research (ANIRCEF). The system integrates a diagnostic expert system able to suggest the correct ICHD-II diagnosis once all clinical characteristics of a patient's headache have been collected. The software has undergone a multicentre validation study to assess: its diagnostic accuracy; the impact of using the software on visit duration; the userfriendliness degree of the software interface; and patients' acceptability of computer-assisted interview. Five Italian headache centres participated in the study. The results of this study validate AIDA Cefalee as a reliable diagnostic tool for primary headaches that can improve diagnostic accuracy with respect to the standard clinical method without increasing the time length of visits even when used by operators with basic computer experience.
Research Interests: Neurology, Neurosurgery, Medicine, Italy, Humans, and 15 moreNeuroradiology, expert System, Patient Satisfaction, Differential Diagnosis, Clinical Sciences, Computer User Interface Design, Diagnostic Accuracy, Computer assisted Diagnosis, Neurosciences, Predictive value of tests, Headaches, Neurological Sciences, Headache disorders, Diagnostic Tool, and Diagnostic errors
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Research Interests: Neurology, Radiology, Neurosurgery, Neuroimaging, Magnetic Resonance Imaging, and 15 moreMedicine, Cerebrospinal Fluid, Brain, Humans, Neuroradiology, Spinal Cord, Headache, Clinical Sciences, Spectrum, X ray Computed Tomography, Clinical Presentation, Neurosciences, Translation for Neurological Sciences, Neurological Sciences, and Intracranial Hypotension
Spontaneous intracranial hypotension (SIH) is a syndrome of low cerebrospinal fluid (CSF) pressure characterised by postural headaches in patients without any history of dural puncture or penetrating trauma. Described by Schaltenbrand in... more
Spontaneous intracranial hypotension (SIH) is a syndrome of low cerebrospinal fluid (CSF) pressure characterised by postural headaches in patients without any history of dural puncture or penetrating trauma. Described by Schaltenbrand in 1938, SIH is thought to result from an occult CSF leak resulting in decreased CSF volume and, consequently, in low CSF pressure. Magnetic resonance imaging of the head and spine has improved the diagnosis of the syndrome showing peculiar radiographic abnormalities including diffuse pachymeningeal enhancement, subdural fluid collections and downward displacement of the cerebral structures. Treatment of SIH headache should start with conservative, non-invasive therapies while epidural blood patch has emerged as the treatment of choice for those symptomatic patients who have failed medical noninvasive approaches.
Research Interests: Neurology, Neurosurgery, Magnetic Resonance Imaging, Medicine, Occult, and 12 moreReview, Cerebrospinal Fluid, Humans, Clinical Sciences, X ray Computed Tomography, Neurosciences, Intracranial Pressure, Headaches, Magnetic resonance image, Neurological Sciences, Epidural Blood Patch, and Intracranial Hypotension
To investigate the presence of Restless Legs Syndrome (RLS) in Cluster Headache (CH) patients compared to headache-free controls. Cross-sectional case-control study of CH patients presenting at tertiary headache centers over the period... more
To investigate the presence of Restless Legs Syndrome (RLS) in Cluster Headache (CH) patients compared to headache-free controls. Cross-sectional case-control study of CH patients presenting at tertiary headache centers over the period January-December 2008. Fifty consecutive patients (6 women and 44 men) of mean age of 39.7 year (standard deviation 10.9) with episodic or chronic CH diagnosed according to ICHD-II criteria and 50 headache-free subjects matched by age and sex were recruited. None of the CH patients had RLS. Six (12%) headache-free controls had RLS. Our data indicate no probable relationship between CH and RLS. However, since both conditions have a circadian rhythm and are associated with altered melatonin secretion, we conjecture that reduced nocturnal melatonin in CH likely allows sustained dopaminergic activity which could be protective against RLS in CH patients.
Research Interests: Pediatrics, Medicine, Dopamine, Melatonin, Humans, and 15 moreCircadian Rhythm, Female, Male, Clinical Sciences, Cluster Headache, Aged, Middle Aged, Adult, Restless Legs Syndrome, Observational Study, Cross Sectional Studies, Neurosciences, Case Control Studies, Restless Leg Syndrome, and dopaminergic
This study validates the method of interviewing only the first-degree relatives indicated by the proband as possible cluster headache sufferers. We interviewed essentially all the first-degree relatives (93%) of 87 probands with cluster... more
This study validates the method of interviewing only the first-degree relatives indicated by the proband as possible cluster headache sufferers. We interviewed essentially all the first-degree relatives (93%) of 87 probands with cluster headache. We found only one new first-degree relative with cluster headache (1/ 40 = 2.5%). The selective interview may be used with confidence as a means of investigating the hereditary component of cluster headache.
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A fixed location unilateral headache suggests involvement of a precise nervous structure, and neuroimaging investigations are essential to seek to identify it. Nevertheless, side-locked primary headaches also occur, although they are... more
A fixed location unilateral headache suggests involvement of a precise nervous structure, and neuroimaging investigations are essential to seek to identify it. Nevertheless, side-locked primary headaches also occur, although they are rare. Side-locked primary headaches are more frequently found in the group of the short-lasting (≤ 4 hours) headaches but long-lasting headache forms may also present with the pain always on the same side, including migraine, tension-type headache, new daily persistent headache and cervicogenic headache. Future studies should address the issue whether patients with side-locked headache form differ from those with non-side-locked form both in terms of natural history and biological markers. Among 63 consecutive chronic cluster headache patients seen by us from 1999 to 2007, 32 (51±) had side shift. We also found that the duration of the chronic condition was significantly longer in those with side shift than those without. The high frequency of side shif...
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Spontaneous intracranial hypotension syndrome (SIH) is a complex pathological entity due to reduction of cerebrospinal fluid (CSF) volume and results into a variegated symptomatology, ranging from orthostatic headache to more severe... more
Spontaneous intracranial hypotension syndrome (SIH) is a complex pathological entity due to reduction of cerebrospinal fluid (CSF) volume and results into a variegated symptomatology, ranging from orthostatic headache to more severe conditions, such as stupor and coma; several attempts have been done in the past to understand the exact pathophysiological mechanisms which underlie its phenomenology, as well as different therapeutic approaches to relieve symptoms and reverse the reduction of overall CSF volume, both focally (in the case of a clear localized CSF leak) or by reversing the pressure gradient between the venous system and the subdural and epidural compartments (in the case of idiopathic SIH). The Authors’ experience is here reported, along with some pathophysiological and neuroradiological implications and considerations.
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The objective of this study is to assess patients’ satisfaction with migraine treatment with frovatriptan (F) or zolmitriptan (Z), by preference questionnaire. 133 subjects with a history of migraine with or without aura (IHS criteria)... more
The objective of this study is to assess patients’ satisfaction with migraine treatment with frovatriptan (F) or zolmitriptan (Z), by preference questionnaire. 133 subjects with a history of migraine with or without aura (IHS criteria) were randomized to F 2.5 mg or Z 2.5 mg. The study had a multicenter, randomized, double-blind, cross-over design, with each of the two treatment periods lasting no more than 3 months. At the end of the study, patients were asked to assign preference to one of the treatments (primary endpoint). The number of pain-free (PF) and pain-relief (PR) episodes at 2 h, and number of recurrent and sustained pain-free (SPF) episodes within 48 h were the secondary study endpoints. Seventy-seven percent of patients expressed a preference. Average score of preference was 2.9 ± 1.3 (F) versus 3.0 ± 1.3 (Z; p = NS). Rate of PF episodes at 2 h was 26% with F and 31% with Z (p = NS). PR episodes at 2 h were 57% for F and 58% for Z (p = NS). Rate of recurrence was 21 (F) and 24% (Z; p = NS). Time to recurrence within 48 h was better for F especially between 4 and 16 h (p < 0.05). SPF episodes were 18 (F) versus 22% (Z; p = NS). Drug-related adverse events were significantly (p < 0.05) less under F (3 vs. 10). In conclusion, our study suggests that F has a similar efficacy of Z, with some advantage as regards tolerability and recurrence.
Research Interests: Treatment Outcome, Adolescent, Italy, Humans, Female, and 19 moreMale, Patient Satisfaction, Patient Preference, Clinical Sciences, Neurological, Aged, Middle Aged, Questionnaires, Adult, Time Factors, Adverse Event, Migraine With Aura, Cross-Over Studies, Neurosciences, Pain Measurement, Translation for Neurological Sciences, Oxazolidinones, Tryptamines, and Neurological Sciences
Recent evidence suggests that spontaneous intracranial hypotension (SIH) is not as rare as previously thought. Orthostatic headache is the prototypical manifestation of SIH, but various headache syndromes have also been reported such as... more
Recent evidence suggests that spontaneous intracranial hypotension (SIH) is not as rare as previously thought. Orthostatic headache is the prototypical manifestation of SIH, but various headache syndromes have also been reported such as migraine-like headache, tension-type headache and non-specific headaches among the others. The International Headache Society (IHS) has recently proposed diagnostic criteria for headache attributed to SIH. Seventy patients consecutively seen at our institution between 1993 and 2005 and diagnosed with SIH were included in the study. SIH diagnosis was confirmed in all patients by brain-enhanced MRI: 23 were males (33%), 47 females (77%) and mean age was 45 years (range 18–69). Follow-up: median value 35 months (range: 8 months-14 years). Time between symptom onset and diagnosis was 4 months (median) (range 15 days-45 months). The IHS (2004) criteria for “Headache attributed to SIH” were applied. Typical brain imaging findings confirmed the diagnosis of SIH in all patients: criteria B and C were fulfilled in all patients. Criterion A of the IHS classification was not fulfilled in 34 (49%) patients. Sixty-two (89%) patients did not fulfil criterion D of the IHS classification; 28 (40%) did not fulfil both criterion A and D. So far, only 2 (3%) fulfilled all IHS criteria for headache attributed to SIH. The IHS criteria for headache attributed to SIH could not classify the headache in most of our SIH patients. A revision of the IHS criteria for headache attributed to SIH is necessary.
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Intracranial hypotension is typically manifested by orthostatic headache. The most frequent underlying factor is cerebrospinal fluid leakage. It has been suggested that dural structural weakness in some connective tissue diseases may be... more
Intracranial hypotension is typically manifested by orthostatic headache. The most frequent underlying factor is cerebrospinal fluid leakage. It has been suggested that dural structural weakness in some connective tissue diseases may be responsible for dural tears and diverticula and consequently leakage. We present a case of spontaneous intracranial hypotension associated with Marfan syndrome and autosomal dominant polycystic kidney disease. The patient was treated successfully with epidural autologous blood patch. Dural involvements of these hereditary connective tissue diseases are also discussed.
Research Interests: Neurosurgery, Magnetic Resonance Imaging, Tinnitus, Humans, Back Pain, and 21 moreFemale, Headache, Neck Pain, Marfan syndrome, The, Differential Diagnosis, Skin, Hearing Loss, Nausea, Vertigo, Skin Diseases, Clinical Sciences, Middle Aged, Adult, X ray Computed Tomography, Craniofacial Surgery, Neurosciences, Audiometry, Magnetic resonance angiography, Severity of Illness Index, and Intracranial Hypotension
Dural sinus thrombosis (DST) is rarely associated with spontaneous intracranial hypotension (SIH). Engorgement of the venous system, caused by the CSF loss that occurs in SIH, is considered to favour the thrombosis, although signs of both... more
Dural sinus thrombosis (DST) is rarely associated with spontaneous intracranial hypotension (SIH). Engorgement of the venous system, caused by the CSF loss that occurs in SIH, is considered to favour the thrombosis, although signs of both SIH and DST are usually seen simultaneously at the first diagnostic MRI. We observed two patients with SIH and DST. Changes in pattern of headaches and MRI findings demonstrated that DST followed SIH. In SIH, the velocity of the blood flow in the dural sinuses may be reduced because of dilatation of the venous system which compensates the CSF loss. Other possible mechanisms seem unlikely on the grounds of both clinical presentation and MRI studies.
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This article briefly reviews the spectrum of headaches associated with Chiari type I malformation (CMI) and specifically analyzes the current data on the possibility of this malformation as an etiology for some cases of chronic daily... more
This article briefly reviews the spectrum of headaches associated with Chiari type I malformation (CMI) and specifically analyzes the current data on the possibility of this malformation as an etiology for some cases of chronic daily headache (CDH). CMI is definitely associated with cough headache and not with primary episodic headaches, with the rare exception of basilar migraine-like cases. With regard to CDH, there is no clear evidence supporting an association with CMI. A magnetic resonance imaging (MRI) study would be justified only in patients showing either a Valsalva-aggravating component or cervicogenic features. Hydrocephalus and low-intracranial pressure syndrome should be ruled out in patients showing tonsillar herniation in an MRI study and consulting due to daily headache.
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Improvement in the biomedical and biotechnological research fields have allowed refinement of the neuromodulation approach in the treatment of a subgroup of medical disorders otherwise refractory to pharmacological treatment, such as... more
Improvement in the biomedical and biotechnological research fields have allowed refinement of the neuromodulation approach in the treatment of a subgroup of medical disorders otherwise refractory to pharmacological treatment, such as chronic primary headaches. Chronic pain conditions imply central sensitisations and functional reorganisation that cannot be quickly or easily reversed. It appears evident that conventional treatment can sometimes be unsuccessful or only partially successful, and that relapse is common. Cluster headache (CH) is the most frequent trigeminal autonomic cephalalgia (TAC) and the most representative of this spectrum of disorders characterised by the association of headache and loco-regional signs and symptoms of facial parasympathetic activation. The striking features of circadian rhythmicity of attacks and circannual periodicity of cluster period, together with the neuroendocrine abnormalities, are suggestive of a neurochronobiological disorder with a central-diencephalic pathogenetic involvement, confirmed by direct evidence in functional neuroimaging studies of ipsilateral posterior hypothalamic activation during cluster attack. In 2000 these findings prompted a functional neurosurgery approach, with the first case of deep brain hypothalamic stimulation (DBS) in a severely disabled chronic CH patient. Since then, 18 implants in our centre and many others in different countries have been performed. Although the outcomes are encouraging, the invasive nature of the technique and the occurrence of rare but major adverse events have suggested a safer peripheral approach with occipital nerve stimulation (ONS).
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Chronic daily headache that does not respond or no longer responds to prophylaxis is commonly encountered at specialist headache centres. Animal and brain imaging studies indicate that peripheral neurostimulation affects brain areas... more
Chronic daily headache that does not respond or no longer responds to prophylaxis is commonly encountered at specialist headache centres. Animal and brain imaging studies indicate that peripheral neurostimulation affects brain areas involved in pain modulation, providing a rationale for its use in these conditions. We examine problems related to the selection of chronic daily headache patients for peripheral neurostimulation. These conditions are often associated with analgesic (including opioid) overuse, and psychiatric or other comorbidities, and the terms used to describe them (chronic migraine, transformed migraine, chronic daily headache and chronic tension-type headache) are insufficiently informative about these patients when proposed for neurostimulation. Longitudinal studies indicate that pre-existing subclinical depressive and anxious states play a key role in chronicisation and that the probability of responding to treatment is inversely related to headache frequency. These considerations suggest the need for extensive characterisation of patients proposed for neurostimulation. We propose that patients being considered for neurostimulation should be followed for at least a year, and that their headache over this time should consistently be frequent (all or most days) and drug refractory. We also propose that only completely drug-resistant (as opposed to partially drug-resistant) patients be considered for neurostimulation unless there are other indications.
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Cluster headache is a primary headache syndrome that is characterized by excruciatingly severe, strictly unilateral attacks of orbital, supraorbital or temporal pain, which last 15-180 min and are accompanied by ipsilateral autonomic... more
Cluster headache is a primary headache syndrome that is characterized by excruciatingly severe, strictly unilateral attacks of orbital, supraorbital or temporal pain, which last 15-180 min and are accompanied by ipsilateral autonomic manifestations (e.g. lacrimation and rhinorrhea). The attacks typically occur with circadian rhythmicity, being experienced at fixed hours of the day or night. In episodic cluster headache, attacks usually occur daily in 6-12-week bouts (cluster periods) followed by remission periods. In chronic cluster headache there is no notable remission. Cluster headache attacks reach full intensity very quickly and abortive agents need to be administered without delay. The pathophysiology of cluster headache is imperfectly understood and treatment has so far been mainly empirical. However, neuroimaging studies have prompted the successful use of hypothalamic stimulation to treat the condition. More recently, the less invasive technique of occipital nerve stimulation has shown promise in drug-refractory chronic cluster headache. This Review discusses both acute and preventive treatments for cluster headache and includes suggestions of how to use the available medications. The rationale, study results and selection criteria for neurostimulation procedures are also summarized, as are the disadvantages of these procedures.
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Drug refractory chronic daily headache (CDH) is a highly disabling condition. CDH is usually regarded as the negative evolution of chronic migraine (CM) and is characterized by high prevalence of psychiatric disorders, especially mood... more
Drug refractory chronic daily headache (CDH) is a highly disabling condition. CDH is usually regarded as the negative evolution of chronic migraine (CM) and is characterized by high prevalence of psychiatric disorders, especially mood disorders. Vagal nerve stimulation (VNS) is an established treatment option for selected patients with medically refractory epilepsy and depression. Neurobiological similarities suggest that VNS could be useful in the treatment of drug-refractory CM associated with depression. The aim of the study was to evaluate the efficacy of VNS in patients suffering from drug-refractory CM and depressive disorder. We selected four female patients, mean age 53 (range 43–65 years), suffering from daily headache and drug-refractory CM. Neurological examination and neuroradiological investigations were unremarkable. Exclusion criteria were psychosis, heart and lung diseases. The preliminary results in our small case series support a beneficial effect of chronic VNS on both drug-refractory CM and depression, and suggest this novel treatment as a valid alternative for this otherwise intractable and highly disabling condition.
Research Interests: Chronic Pain, Treatment Outcome, Humans, Chronic Disease, Female, and 14 moreDrug Resistance, Vagal Nerve Stimulation, Follow-up studies, Depressive Disorder, Clinical Sciences, Neurological, Aged, Middle Aged, Vagus Nerve Stimulation, Adult, Mood Disorder, Neurosciences, Translation for Neurological Sciences, and Neurological Sciences
Cluster headache (CH), paroxysmal hemicrania (PH), and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome) are primary headaches grouped together as trigeminal autonomic... more
Cluster headache (CH), paroxysmal hemicrania (PH), and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome) are primary headaches grouped together as trigeminal autonomic cephalalgias (TACs). All are characterized by short-lived unilateral head pain attacks associated with oculofacial autonomic phenomena. Neuroimaging studies have demonstrated that the posterior hypothalamus is activated during attacks, implicating hypothalamic hyperactivity in TAC pathophysiology and suggesting stimulation of the ipsilateral posterior hypothalamus as a means of preventing intractable CH. After almost 10 years of experience, hypothalamic stimulation has proved successful in preventing pain attacks in approximately 60% of the 58 documented chronic drug-resistant CH patients implanted at various centers. Positive results have also been reported in drug-resistant SUNCT and PH. Microrecording studies on hypothalamic neurons are increasingly being performed and promise to make it possible to more precisely identify the target site. The implantation procedure has generally proved safe, although it carries a small risk of brain hemorrhage. Long-term stimulation is proving to be safe: studies on patients under continuous hypothalamic stimulation have identified nonsymptomatic impairment of orthostatic adaptation as the only noteworthy change. Studies on pain threshold in chronically stimulated patients show increased threshold for cold pain in the distribution of the first trigeminal branch ipsilateral to stimulation. When the stimulator is switched off, changes in sensory and pain thresholds do not occur immediately, indicating that long-term hypothalamic stimulation is necessary to produce sensory and nociceptive changes, as also indicated by clinical experience that CH attacks are brought under control only after weeks of stimulation. Infection, transient loss of consciousness, and micturition syncope have been reported, but treatment interruption usually is not required.
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Primary cluster headache (CH) is an excruciatingly severe pain condition. Several pharmacologic agents are available to treat chronic CH, but few double-blind, randomized clinical trials have been conducted on these agents in recent... more
Primary cluster headache (CH) is an excruciatingly severe pain condition. Several pharmacologic agents are available to treat chronic CH, but few double-blind, randomized clinical trials have been conducted on these agents in recent years, and the quality of the evidence supporting their use is often low, particularly for preventive agents. We recommend sumatriptan or oxygen to abort ongoing headaches; the evidence available to support their use is good (Class I). Ergotamine also appears to be an effective abortive agent, on the basis of experience rather than trials. We consider verapamil and lithium to be first-line preventives for chronic CH, although the trial evidence is at best Class II. Steroids are clearly the most effective and quick-acting preventive agents for chronic CH, but long-term steroid use carries a risk of several severe adverse effects. We therefore recommend steroids only if verapamil, lithium, and other preventive agents are ineffective. In rare cases, patients experience multiple daily cluster headaches for years and are also refractory to all medications. These patients almost always develop severe adverse effects from chronic steroid use. Such patients should be considered for neurostimulation. Occipital nerve stimulation is the newest and least invasive neurostimulation technique and should be tried first; the evidence supporting its use is encouraging. Hypothalamic stimulation is more invasive and can be performed only in specialist neurosurgical centers. Published experience suggests that about 60% of patients with chronic CH obtain long-term benefit with hypothalamic stimulation.
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Various diagnostic criteria have been proposed for chronic daily headaches. We tested the recently proposed revised criteria of the International Headache Society in a sample of patients with chronic daily headaches, most of whom were... more
Various diagnostic criteria have been proposed for chronic daily headaches. We tested the recently proposed revised criteria of the International Headache Society in a sample of patients with chronic daily headaches, most of whom were overusing acute medications, to assess their applicability in clinical practice compared to alternative classification systems.
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Background.—Trigeminal autonomic cephalgias (TACs) and trigeminal neuralgia are short-lasting unilateral primary headaches whose study is providing insights into craniofacial pain mechanisms. We report on 2 patients in whom trigeminal... more
Background.—Trigeminal autonomic cephalgias (TACs) and trigeminal neuralgia are short-lasting unilateral primary headaches whose study is providing insights into craniofacial pain mechanisms. We report on 2 patients in whom trigeminal neuralgia coexists with the TACs paroxysmal hemicrania and SUNCT.Conclusion.—Coexistence of trigeminal neuralgia with various TAC forms suggests a pathophysiological relationship between these short-lasting unilateral headaches.
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The introduction of neurostimulation procedures for chronic drug-resistant primary headaches has offered new hope to patients, but has also introduced new problems. The methods to be used in assessing clinical outcomes and monitoring... more
The introduction of neurostimulation procedures for chronic drug-resistant primary headaches has offered new hope to patients, but has also introduced new problems. The methods to be used in assessing clinical outcomes and monitoring treatment efficacy need careful attention. The International Headache Society guidelines recommend that treatment efficacy should be monitored by getting patients to report the number of attacks per day, in a headache diary. The headache diary is a fundamental instrument for objectively assessing subjective pain in terms of headache frequency, intensity and duration and analgesic consumption. The huge discrepancy sometimes reported between patient satisfaction and headache improvement suggests that patient satisfaction should not be a primary efficacy endpoint, and more importantly should not be put forward as an argument in establishing the efficacy of highly experimental neurostimulation procedures.