Renata Rao

Endothelial nitric oxide synthase (Glu298Asp) polymorphism is an independent risk factor for migraine with aura

Objective.—The aim of the present study was to evaluate whether the functional endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism, which has been demonstrated to decrease the endothelial NOS activity, might be a risk factor for migraine.

Investigating the association between Notch3 polymorphism and migraine.

Objective.—The aim of the present study was to evaluate whether the functional Notch3 polymorphism T6746C, which is not causative for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), might be a risk factor for migraine.

Where SUNCT contacts TN: a case report.

Background.—Short‐lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) and trigeminal neuralgia (TN) are unilateral painful conditions that can share the same triggering factors, autonomic features and the main location, as well as the cyclically recurrent crises. Both these syndromes are associated with a high percentage of findings of vascular malformation touching the trigeminal nerve, suggesting a pathophysiological relationship.

Cerebrovascular risk factors and MRI abnormalities in migraine

Case series have demonstrated an increased incidence of white matter lesions (WMLs) in patients with migraine. It is controversial whether the evidence of subclinical brain lesions relates to a higher risk of cerebrovascular disease. The objective of this study was to evaluate the association between magnetic resonance imaging (MRI) subclinical brain lesions and cerebrovascular risk factors (hyperhomocysteinaemia, MTHFR genotype, patent foramen ovale, hypertension, smoking and hypercholesterolaemia). From our database of 1201 patients followed at our Headache Clinic since September 2003 we analysed the MRI findings of 253 individuals. All MRI were blindly analysed by a second neuroradiologist (C.A.) and patients with WMLs (study group) were evaluated. In order to assess the association of WMLs with specific vascular risk factors, patients with WMLs were matched, according to age, sex and ICHD II diagnosis, with an equal number of individuals with normal MRI (control group). Headache was classified by the International Classification of Headache Disorders (ICHD 2004) criteria. We did not find any statistically significant difference between the two groups with regard to the presence of the cerebrovascular disease risk factors considered. Our results confirm that the WMLs are not related to the cerebrovascular disease risk factors.

Central nervous system angiitis in Hodgkin’s disease

Dear Sirs, Hodgkin’s disease (HD) is a B-lymphoid neoplasm that can cause neurological dysfunction due to rare central nervous system (CNS) invasion or most frequently to CNS paraneoplastic syndromes or treatment-related toxicity [1]. We report a patient with HD in complete remission who suffered CNS angiitis. A 20-year-old man was admitted to our department because of headache of insidious onset, nausea, vomiting, and diplopia. He suffered from a mixed-cellularity HD, stage III B, diagnosed 8 months before, in complete remission after six cycles of chemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) and radiotherapy. Neurological examination revealed paresis of the right VIth cranial nerve, bilateral papilledema, and spontaneous speech reduction. Routine and autoimmunity (antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, serum C3 and C4, serum cryoglobulins, antiphospholipid antibodies) blood tests were unremarkable. Cerebrospinal fluid (CSF) analysis showed pleocytosis (white blood cells, 66/mm), increased proteins concentration (50 mg/dl), negative cultures and small, mature lymphocytes, with normal morphology. Brain magnetic resonance imaging (MRI) showed left frontotemporal hyperintensity in the T2/FLAIR sequences (Fig. 1a–c), and diffuse small vessels enhancement after gadolinium administration, which was more severe in the left temporal lobe (Fig. 1d). Overall, CSF and imaging findings were strongly suggestive of CNS angiitis and a diagnosis of possible paraneoplastic CNS angiitis according to the criteria of Dalmau and Rosenfeld was performed [2]. Intravenous methylprednisolone (1,000 mg/day for 5 days) followed by oral prednisone (1 mg/kg/day) were started. Considering the supposed paraneoplastic etiology of CNS angiitis, intravenous immune globulin (400 mg/kg/ day for 5 days) were administered concurrently with corticosteroid treatment. During the two successive weeks, the patients progressively ameliorated up to complete symptoms resolution. Brain MRIs performed 1 and 3 months after the episode were negative (Fig. 2). At last follow-up, 1 year after the end of chemotherapy, the CT and PET scan revealed the presence of a large mediastinal mass, with histological diagnosis of thymic hyperplasia. In the meantime, mild symptoms and radiological signs of CNS angiitis re-appeared. CNS vasculitis associated with HD was first described by Greco and Colleagues in 1976 [3] and was reported in 17 cases. Although its pathophysiology is not completely understood, it may be considered a paraneoplastic disorder associated with a deregulation of the immune system. Differently from other paraneoplastic syndromes of the CNS [2], in HD it often arises after lymphoma diagnosis [4]. Clinical presentation includes headache, nausea, vomiting, seizures, and mental status change. CSF analysis usually reveals mild lymphocytic pleocytosis and protein increase [5]. CSF investigation is mandatory to rule out A. Morotti (&) M. Codella R. Rao A. Pezzini A. Padovani Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Piazzale Spedali Civili 1, 25125 Brescia, Italy e-mail: a.morotti@ymail.com

OnabotulinumtoxinA in chronic migraine: long-term efficacy in a prophylactic medication free cohort

Chronic migraine (CM) is a debilitating neurologic disorder defined as headaches occurring on ≥ 15 days per month for more than 3 months, with headaches having migraine features on ≥ 8 days per month. Patients with chronic migraine typically have a history of episodic migraine headaches that increase in frequency over a period of months to years until patients experience daily or near-daily, low-grade migraineous and nonmigraineous headaches with intermittent attacks of severe migraine. CM affects approximately 1.4 to 2.2% of adults worldwide with an important economic burden and impact in quality of life. Both frequency of attacks, severity of pain, and associated symptoms have a major role on migraine-related disability. The current understanding of headache pathophysiology is evolving. For patients affected by CM, a prophylactic headache treatment regimen is highly recommended to reduce the frequency, severity, and disability. OnabotulinumtoxinA is a focally acting protein that inhibits the release of the neurotransmitter acetylcholine from the presynaptic nerve endings and blocks the neuronal release of nociceptive mediators such as substance P, glutamate, and calcitonin gene-related peptide (CGRP) in the periphery, which suggests it may possess peripheral antinociceptive activity. The inhibition of nociceptive mediators in the periphery may reduce central sensitization, perhaps by inhibiting afferent inputs to the central nervous system, thereby reducing inflammatory signals to sensitized regions in the brain. Its biological effects are transient, and within approximately 3 months, normal neuronal signaling is restored. The recently published PREEMPT [1] and COMPEL [2] studies established the safety and efficacy of OnabotulinumtoxinA for treatment of chronic migraine. The a im of the presen t s tudy was to assess OnabotulinumtoxinA long-term efficacy in CM patients as a prophylactic agent alone.Moreover, subjects who presented with a diagnosis of chronic migraine with medication overuse headache were treated directly with OnabotulinumtoxinA, sidestepping withdrawal interventions, althought such bridge therapies are generally regarded as crucial for subsequent prophylaxis’ efficacy. The study was conducted at the Headache Centre of Neurological Department of ASST Spedali Civili of Brescia. We evaluated prospectively all patients aged 18 to 65 years with CMwith orwithout a diagnosis ofmedical overuse headache between 1 January 2015 and 31 December 2017. Diagnosis was made according to the ICHD III beta criteria [3]. During the study, preventive treatments were not allowed. We collected data concerning demographic variables: pain site, disease duration, previous prophylaxis therapies, monthly number of days with headache (distinguished according with intensity of pain), and symptomatic drug consumption (triptans, NSAIDs and combination analgesics). We collected the same variables at each subsequent evaluation every 3 months by analysis of headache diary provided at our center. Migraine-induced disability was assessed using the Migraine Disability Assessment Score Questionnaire (MIDAS) at baseline and 3, 6, and 9 months after treatment. Patients were injected OnabotulinumtoxinA according to the PREEMPT protocol. We administered 155 units intramuscularly in 31 sites. At the investigator’s discretion, an additional 20 units could be administered using a follow-the-pain strategy based on the patient’s report of predominant pain location. The primary endpoint was to evaluate the reduction in the headache frequency at 3, 6, and 9 months after the discontinuance of the treatment. Secondary endpoints were evaluation of reduction in intensity of pain, symptomatic medication intake, * Francesca Schiano di Cola francescaschiano@hotmail.it

Headaches in the elderly, in an out-patient population over 60 years of age

Headache in community-living adults age 65 and older is the 10th most common reported symptom in women and the 14th most common in men. Although the prevalence of headache declines with age, approximately 10% of women and 5% of men at age 70 experience severe recurrent or constant headaches. Much less is known about the evolving clinical profile of migraine over the life span. The present study aimed to investigate every type of headaches in elderly people and was carried out on a group of patient over 60 years of age, selected from 771 consecutive patients to the Headache Centre in the period January 2011-December 2011. Methods This study was conducted in a university-based outpatient headache clinic. The study population consisted of 771 consecutive headache patients treated by the authors in one year. Variables studied included gender, headache duration in years, aura, headache characteristics, associated symptoms, presence of allodynia, headache frequency, headache days, and disability. Amedical history of these patients was also recorded. The headache diagnosis were made according to ICHD-2 criteria. Patients were stratified by age into 3 groups: group 1, 16 to 39, group II, 40 to 59, and group III, 60 years and older. Results A total of 605 patients were female and 166 were male, mean age was 36.9 + 13.6 years (range 16 to 84), average headache duration 18.4 years, and headache days/month 7.9. The average age of older headache suffers was 66.5 years. There were 48 female patients (7.9%) and 6 male patients (3.6%) in the older age group. There were no differences between the groups in gender and other variables assessed. The 60+ age group tended to have more chronic migraine and to use more acute medication. Discussion In our population chronic migraine and medication overuse don’t decline over time. We found that, compared with younger patients, older headache patients had not a “lesser migraine” as reported in previous studies. Studies of community-based headache population are warranted to define the influence of age on the full spectrum of migraine.