Correction to: The Italian Dystonia Registry: rationale, design and preliminary findings.

In the original article, Gina Ferrazzano was affiliated to Department of Neurology and Psychiatry, Neuromed Institute IRCCS, Sapienza University of Rome, Pozzilli, Italy.The corrected affiliation should be: Neuromed Institute IRCCS, Pozzilli, IS, Italy.

Pathogenesis of chronic cluster headache and bouts: role of tryptamine, arginine metabolism and α1-agonists.

The aim of this study was to explore the possible role of tryptamine in the pathogenesis of chronic cluster headache along with that of adrenaline and noradrenaline (α-agonists) together with arginine metabolism in the origin of cluster bouts. Plasma levels of tyramine, tryptamine, serotonin, 5-hydroxyindolacetic acid, noradrenalin, adrenalin and the markers of arginine metabolism such as arginine, homoarginine, citrulline, ADMA and NMMA, were measured in 23 chronic cluster headache patients (10 chronic cluster ab initio and 13 transformed from episodic cluster) and 28 control subjects. The plasma levels of tyramine, tryptamine, noradrenalin and adrenalin were found several times higher in chronic cluster headache patients compared to controls, whereas the plasma levels of arginine, homoarginine and citrulline were significantly lower. No differences were found in the plasma levels of serotonin, 5-hydroxyindolacetic, ADMA and NMMA between chronic cluster headache patients and control subjects. These results provide support for a role of tryptamine in the pathogenesis of chronic cluster headache and, in particular, in the duration of the cluster bouts. In addition, the low levels of the nitric oxide substrates together with the high levels of noradrenalin and adrenalin suggest an activation of endothelial TAAR1 receptors followed by the release of nitric oxide in the circulation that may constitute the final step of the physiopathology of cluster crisis.

The Italian Dystonia Registry: rationale, design and preliminary findings.

The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.

Migraine attacks in the pharmacy: a survey in Piedmont, Italy.

Headache patients often consult a pharmacist in an attempt to obtain momentary pain relief without having been given any previous expert advice. A specific questionnaire was distributed to the pharmacies in order to assess the patterns of use and dispensing of analgesic medications to the headache patient who turns to the pharmacist for relief of a painful attack. This study aimed at identifying migraine patients who self-medicated, with further end points including whether these patients shared any particular clinical characteristics, the most common type of analgesic medications used, and what, if anything, was recommended by the pharmacist; lastly, which health care professional, if any, routinely managed the patient's headaches. A total of 9,100 questionnaires were distributed to the pharmacies and the complete 3,065 were included in the database. The ID Migraine Screener Test was used to classify subjects into 4 groups: "Definite migraine" (3/3 positive answers: n = 1,042; 34 %), "Probable migraine" (2/3: n = 969; 31.6 %), "Unlikely migraine" (1/3: n = 630; 20.5 %), and "Other headaches" (0/3: n = 424; 13.8 %). Only Definite and Probable migraines (n = 2,011) are considered in this paper. Amongst the drugs usually taken by the patients, NSAIDs were more common in the Probable migraine group (60.7 %) than in the Definite migraine (44.7 %) group (p < 0.001). On the contrary, triptans were more commonly used by the Definite migraine group (42.9 %) than the Probable migraine (23.7 %) group (p < 0.001), and combination drugs were preferentially (p < 0.001) chosen by the Definite (13.8 %) rather than the Probable migraine group (8.7 %). A total of 29.2 % of respondents reported that for the management of their headaches, they did not avail themselves of any type of professional healthcare, such as their general practitioner, a headache specialist, or a Headache Center.

Relationship between primary headache and nutrition: a questionnaire about dietary habits of patients with headache.

The role of food associated with the headache has been the subject of scientific research since 1900, especially for migraine patients. A substantial proportion of patients (ranging from 12 to 60 %) report that their migraine attacks may be precipitated by dietary elements, certain eating habits (fasting) and abuse (caffeine and alcoholic beverages abuse and withdrawal). The biological mechanism by means of triggers in general and food in particular precipitate migraine attacks remains obscure. Based on the data in the literature, we performed an osservational study searching for possible correlations between nutrition and primary headaches. We enrolled 50 consecutive patients from the Headache Center of the Neurology Department of Hospital "Cardinal Massaia" of Asti and submitted them a 14-item questionnaire for the assessment of relationship between primary headache and food. Our preliminary data, although the follow up is still in progress, show that there are strong associations between the onset of the headache and dietary habits. It will be necessary to analyze a larger sample in order to draw more precise conclusions on this topic.

Primary headache and epilepsy: a multicenter cross-sectional study.

The prevalence and characteristics of interictal headache, epilepsy and headache/epilepsy comorbidity were assessed in 858 women and 309 men aged 18-81 years from headache and epilepsy centers in Italy. The research hypothesis was that comorbidity among patients with either disorder would be expected to be higher than in the general population. Interictal headache was diagnosed in 675 cases (migraine 482; tension-type headache 168; other types 25), epilepsy in 336 (partial 171; generalized 165) and comorbidity in 156 (1.6% from headache centers; 30.0% from epilepsy centers). Patients with epilepsy, headache and comorbidity differed in a number of demographic and clinical aspects. However, for both headache and epilepsy, a family history of the same clinical condition was equally prevalent in patients with and without comorbidity. These findings do not support the purported association between headache and epilepsy.

Pathophysiology of migraine chronification.

Migraine is a prevalent, disabling, undiagnosed and undertreated disease in neurological practice. It is a chronic, recurrent disorder with episodic manifestations that are progressive in some individuals with clinical, physiological and anatomical bases. Progression may be due to mechanisms generating the migraine attacks or to the activation generated by the attacks. Potentially remediable risk factors for chronification include frequency of migraine attacks, obesity, excessive use of medications, caffeine overuse, stressful life events, depression, sleep disorders and cutaneous allodynia.

Greater occipital nerve block in chronic migraine.

Headache syndromes often involve occipital and neck symptoms suggesting a functional connectivity between nociceptive trigeminal and cervical afferents. Several studies have suggested that pain relief in migraine and other types of headache can be achieved by local injections of steroids, local anaesthetics or a mixture of both in the area of greater occipital nerve (GON). Usually greater occipital nerve block (GONB) is performed by using local anaesthetics alone or with steroid. The rationale of performing a GONB for the treatment of chronic headache states is on the anatomical connections between trigeminal and upper cervical sensory fibres at the level of the trigeminal nucleus caudalis. However, the reason for the improvement after GONB in primary headache is unknown. The objective of this study is to determine whether adding triamcinolone to local anaesthetics increased the efficacy of GONB and trigger point injections (TPIs) for chronic migraine (TM). Patients with TM were randomized to receive GONB and TPIs using lidocaine 2% and bupivacaine 0.5% + either saline or triamcinolone 40 mg. Particularly, a 10-ml syringe containing 4.5 ml of lidocaine 2%, 4.5 ml of bupivacaine 0.5% and 1 ml of either saline (group A) or triamcinolone 40 mg/ml (group B) was prepared for each patients. Patients were given bilateral GONB and TPIs in the cervical paraspinal and trapezius muscles bilaterally. 2 ml were injected into each GON at the medial third of the distance between the occipital protuberance and the mastoid process. In addition, 0.5 ml was injected into each of the 12 trigger points. The total injected volume was 10 ml. The primary outcome measure was the change in mean headache severity from before injection to 20 min after in the two groups. Secondary outcome measures were the change in mean neck pain, photophobia and phonofobia severity from before injection to 20 min after in the two groups. Patients documented headache and severity of associated symptoms for 4 weeks after injection. Changes in symptom severity were compared between the two groups. Thirty-seven patients were included. Twenty minutes after injection, mean headache severity decreased by 3.2 points in group A (p < 0.01) and by 3.1 points in group B (p < 0.01). Mean neck pain severity decreased by 1.5 points in group A (p < 0.01) and by 1.7 points in group B (p < 0.01). Mean duration of being headache-free was 2.7 +/- 3.8 days in group A and 1.0 +/- 1.1 days in group B (p = 0.67). None of the outcome measures differed significantly between the two groups. Both treatments were full tolerated. In our study, adding triamcinolone to local anaesthetic when performing GONB and TPIs was not associated with improved outcome in the sample of patients with TM. In both groups, the procedure resulted in significant and rapid relief of headache, neck pain, photophobia and phonofobia.

Neurophysiology and neuromodulators.

Migraine is an episodic brain disorder that results in significant morbidity. Antiepileptic drugs (neuromodulators) are increasingly recommended for migraine prevention because of placebo-controlled double-blind trials that prove them effective. Cortical spreading depression (CSD) is thought to be the pathophysiological correlate of the neurological symptoms in migraine with aura and neuromodulators may act on mechanisms involved in the initiation of CSD itself. Inhibition of trigeminocervical complex directly, or neurons that modulate sensory input, are also plausible mechanisms for the actions of neuromodulators in preventive therapy in migraine. Although it is unlikely that a single phenomenon serves as the only link between migraine and epilepsy, the neuronal hyperexcitability that may contribute to each condition may explain the effect of these drugs for both conditions.

Medical-legal issues in headache: penal and civil Italian legislation, working claims, social security, off-label prescription.

Primary headaches can be considered simultaneously as symptom and disease itself, while secondary headaches are expressions of a pathological process that can be systemic or locoregional. Because of its subjective features, headache is often difficult to assess and quantify by severity, frequency and invalidity rate, and for these reasons it has often been implicated in legal controversies. Headache has seldom been considered in the criminal law, except when it represents a typical symptom of a disease whose existence can be objectively assessed (i. e. raised intracranial pressure). Therefore, in civil legislation it is not yet coded to start claiming for invalidity compensation. In particular, one of the most debated medical-legal questions is represented by headaches occurring after head injury. Headache is often the principal symptom at the beginning of several toxic chronic syndromes, with many implications, especially in working claims, and, more recently, it may be referred to as one of the most frequent symptoms by victims of mobbing (i. e. psychological harassment in the workplace). The National Institute for Industrial Accident Insurance (INAIL) scales (instituted by the law 38/2000) mention the "Subjective cranial trauma syndrome" and give an invalidity rate evaluation. With reference to other headache forms, no legislation really exists at the present time, and headache is only considered as a symptom of a certain coded disease. Requests for invalidity social pension and the question of off-label prescriptions (drug prescription for a disease, without formal indication for it) are other controversial matters.

Typical facial neuralgias.

Neuralgia denotes a sharp, shooting, lancinating pain that is momentary but characteristically recurs. It may be precipitated by touch to a sensitive area ("trigger zone"), or may occur spontaneously. Cranial neuralgias are commonly distinct in two groups: typical neuralgias and atypical facial pain. Unlike headache syndromes, which are mediated centrally, neuralgias are more characteristic of peripheral nerve localisation. Neuralgias may follow nerve trauma, herpes zoster infections or may arise spontaneously. The management of this group of painful conditions is complicated by the area of the body involved and the interaction of organic and psychological factors.

Neurophysiological tests in primary headaches.

An impressive number of studies regarding the usefulness of neurophysiological procedures in primary headaches have been performed, but some of their results are difficult to interpret. However electrophysiological methods are useful to investigate peripheral and central mechanisms underlying this disorders. Taken globally, this results argue in favour of the neuronal pathogenesis of migraine as a final result of modified brainstem inputs to the cortex and/or consequence of a functional neuronal derangement. In this paper are briefly reviewed some of the principal data nowadays reported.

Neurophysiology of pain.

The transmission of pain-related information from the periphery to the cortex depends on signal integration at three levels of the nervous system: the spinal medulla, brainstem and telencephalon. In fulfilling its task of safeguarding human health, pain may develop as a result of damaged or altered primary afferent neurons (stimulus-dependent) or arise spontaneously without any apparent causal stimulus (stimulus-independent). Hyperalgesia (i.e. an exaggerated perception of pain after a painful stimulus) is due to an anomaly in the processing of nociceptive inputs in the central and peripheral nervous systems leading to the activation of the primary afferents by stimuli other than the usual stimuli.

Chronic post-traumatic headache associated with minor cranial trauma: a description of cephalalgic patterns.

We studied a group of 93 patients who had not previously suffered headache and who were consecutively admitted to the Emergency Department of the hospitals of Novara and Borgomanero, Italy because of a cranial trauma definable as minor according to the current International Headache Society (IHS) criteria. Two weeks after admission, all patients underwent a semi-structured interview which revealed that 24 (25.8%) had headache; 21 of these (22.5% of the original 93 patients) also had headache when they underwent a second interview eight weeks after the traumatic event. These 21 patients were diagnosed as having chronic post-traumatic headache associated with minor cranial trauma (5.2.2 of the IHS classification), and the prevalent clinical pattern of headache presentation was examined with the aim of attributing the fourth IHS classification code number. Eighteen of the 21 patients were found to have a tension-type pattern (5.2.2.2), and the remaining three had migraine (5.2.2.1); none had cluster headache (5.2.2.3). These data demonstrate a large prevalence of tension-type headache in patients with class 5.2.2 post-traumatic headache, and confirm the results of previously published studies that were not based on the diagnostic criteria of the current classification.

[Correlated study of visual evoked potentials-polyneuropathy in diabetic patients without retinopathy]. / Studio correlato potenziali evocati visivi-polineuropatia in pazienti diabetici non retinopatici.

The functional study of visual pathways by means of pattern reversals VEPs (visual evoked potentials) was used as a noninvasive method in the study of diabetic patients, but the correlations between alterations in VEPs and the involvement of peripheral nervous system were not explored. Among 35 diabetic patients not suffering from retinopathy, we tested early deteriorations in visual pathways by means of pattern reversals VEPs and we considered similarities between these alterations, clinical metabolic parameters of the disease and clinical and paraclinical aspects of polyneuropathy (PNP). Four of these patients were insulin-dependent and 31 non-insulin-dependent, all with normal electroretinography and fluorangiography. Monitoring control of diabetes was performed by measuring hemoglobin HbA1. The control group was composed of 35 healthy subjects with normal neurologic and ophthalmologic examinations and normal visual acuity. In all subjects we tested four peripheral nerve conduction velocities (PNCV) (sensory and motor conduction of median nerve, motor conduction of peroneal nerve, anthidromic sensory conduction of sural nerve) diabetic patients were distributed in two groups according to the presence (group A, 15 patients) or absence (group B, 20 patients) of polyneuropathy. Pattern reversals PEVs were recorded after mono and binocular stimulation; screen was 25 x 18 cm with black and white check board pattern, check size 1.1 cm. Subject-to-stimulus distance was 1 m, corresponded to a visual angle of 38 degrees. Active electrode were located in Oz, O1 and O2, reference electrode in Fz.(ABSTRACT TRUNCATED AT 250 WORDS)

[Neurologic manifestations of lupus erythematosus]. / Manifestazioni neurologiche in corso di lupus.

A nervous system involvement is common in systemic lupus erythematosus, and may be the initial manifestation of the disease. The spectrum of nervous system involvement is wide, and encompasses almost the whole range of neurological diseases. The neurological lupus is divided into a primary and a secondary group, and in the latter the pathogenetic role is supported by drugs and by organic and functional changes in the other organs and systems. In secondary neurological lupus, when a clinical picture of a focal cerebral injury is sustained by the presence of lupus anticoagulants, the prognosis is strict and the treatment problematic. Finally, among the primary neurological lupus it is important to distinguish two subsets of acute and subacute neurological lupus, because of differences in its management and prognosis.

Major depression in Parkinson's disease and the mood response to intravenous methylphenidate: possible role of the "hedonic" dopamine synapse.

The euphoric response to equivalent doses of intravenous methylphenidate (MTP) was assessed in a group of 13 Parkinsonian patients affected by major depression, in a group of 11 nondepressed Parkinsonians, in a group of 14 nonparkinsonian subjects suffering from major depression, and finally in a group of 12 controls with no CNS or psychiatric disease. Subjects of all four groups were matched for age, sex and other main characteristics. Depressed and nondepressed Parkinsonians were also matched for duration and severity of illness, and for the type of antiparkinsonian treatment. The response to MTP was evaluated in the context of a double-blind, placebo-controlled study. Parkinsonian patients with major depression exhibited a significant lack of sensitivity to the euphoriant effects of MTP, in comparison with the other three groups. Euphoria produced by central stimulants has been shown to depend on the activity of a dopamine synapse in humans, which is thought to be situated at the limbic terminals of dopamine neurons located in the ventral tegmental area. Degeneration of this system may have predisposed our Parkinsonian patients to major depression.

Isolated hypophyseal tuberculoma: case report.

A 45-year-old woman, lifelong resident in Turin presented an isolated tuberculous granuloma of the hypophysis with no other systemic localizations. Diagnosis could be established only by biopsy. With antituberculous therapy the intracellular tumor regressed but not the endocrine disorders.

Analgesic action of methylphenidate on parkinsonian sensory symptoms. Mechanisms and pathophysiological implications.

Intravenous administration of methylphenidate hydrochloride, a central stimulant, was unexpectedly found to exert a potent analgesic effect on primary sensory symptoms in a group of patients with Parkinson's disease. This effect, which has now been studied in a short-term, double-blind, placebo-controlled experiment, subsequently disappeared if patients were pretreated with a beta-blocker or with a serotonin antagonist. Cerebrospinal fluid monoamine metabolites were determined in some of these patients, and the 5-hydroxyindoleacetic acid level was found to be significantly lower than in parkinsonian patients without pain and in normal volunteers. Given the mechanism of action of methylphenidate on the central nervous system, the adrenergic and serotoninergic mediation of its analgesic effect, and the demonstration of impaired central serotonin metabolism in the patient group, it is concluded that not only central dopaminergic deficiency but also altered noradrenergic and serotoninergic transmission in the spinal cord are quite likely to play a role in the pathophysiology of pain in Parkinson's disease.