Apathy in Parkinson's disease: differences between caregiver's report and self-evaluation.

Apathy is a state of diminished goal-directed speech, motor activity and emotions. The prevalence of apathy in Parkinson's disease (PD) ranges from 16 to 62%. Several studies have investigated the relationships between apathy and other dimensions of PD, but little is known about possible discrepancies between self-evaluation (SE) and caregiver reporting (CR) of this symptom. The aim of this study is twofold: 1) to investigate the differences in apathy evaluations according to the point of view from which apathy is reported (SE vs CR); 2) to identify the possible relationships between each of the two evaluations (SE and CR) and cognitive and affective dimensions of PD. Forty-eight patients with PD were assessed using the Apathy Evaluation Scale (AES) in its SE and CR versions (AES-SE and AES-CR); cognitive, affective and behavioral symptoms were also assessed. AES-SE scores were significantly higher than AESCR ones. Neither AES version correlated with depression, whereas both correlated with motor impairment, disease stage and behavioral symptoms. Mini-Mental State Examination and Frontal Assessment Battery scores showed significant negative correlations only with AES-SE scores. Our findings suggest that the point of view from which apathy is seen can lead to significant discrepancies, even when using the same tool. This should be taken into account in order to obtain correct assessment of this disabling and distressing symptom.

The role of diet and lifestyle in adolescents with headache: a review.

Several dietary habits and lifestyles can be associated with different headache types or with their progression to chronic forms. Different population-based studies have tried to investigate this relationship with poor or contradictory results. We shortly reported the current knowledges available in literature in this regard, paying particular attention to the role that certain factors play in modifying frequency and intensity of headache in adults and in adolescents. Future studies are necessary to clarify the real weight which the different factors have in natural history and in clinic evolution of headache, especially in adolescence, but the already known data suggest an important modulating action. If they will be confirmed, these results will be likely to influence clinical practice as well to address educational programs in preadolescents and adolescents.

Headache, eating and sleeping behaviors and lifestyle factors in preadolescents and adolescents: preliminary results from an Italian population study.

Several dietary and lifestyle habits can be associated with headaches or with their progression to chronic forms in adults. We report the results of the first population study performed in Italy on a sample of preadolescent and adolescent students to assess the possible association between headache and specific habits and lifestyle factors. Preliminary data from 800 questionnaires showed that 365 subjects had headaches, which were of moderate-severe intensity, associated with anorexia, and caused absence from school in more than 50 % of students. The main finding was the evidence of a clear association between headache and irregular intake of meals (especially irregular breakfast) and sleep disturbance with significant differences when subjects with and without headache were compared. If confirmed, these results are likely to influence clinical practice as well to address educational programs in preadolescents and adolescents.

Migraine and depression: common pathogenetic and therapeutic ground?

Migraine and depression are recognized as comorbid disorders on the basis of several epidemiological data and on the possibility of shared mechanisms. On the other hand, there is a lack of studies concerning therapeutic strategies in patients with this comorbidity. The aim of this paper is to briefly review the literature about the migraine and depression comorbidity and on the putative common neurobiological mechanisms, as well to discuss the possible therapeutic options in treating patients with both disorders.

Undertreatment in patients with primary headaches attending headache centres.

Undertreatment in patients with primary headaches was evaluated in 600 patients attending 7 headache centres in Lombardy by assessing the rates of acute and prophylactic treatments used before the first visit and the rates of prescription of acute and prophylactic treatments after the visit at the headache centre. Our results clearly showed that most headache patients are likely to receive suboptimal treatments, confirming the utility of headache centres as well as the need for promoting education of GPs and the development of appropriate networks to reduce undertreatment rates, in order to highlight the negative impact caused by primary headache on individuals and on the society.

Migraine prophylaxis: key points for the practising clinician.

Migraine is a significant burden on individuals and society. Patients with most severe forms require preventive treatments, whose aim is to reduce the frequency and severity of attacks and consequently the overall impact of migraine. Although various medications are available for migraine prophylaxis, only a minority of migraineurs receive these drugs. This brief paper summarizes the most important indications for starting migraine prophylaxis, and provides an overview of the salient characteristics of available preventive drugs, to guide the choice of the most appropriate medication for a given patient.

Underdiagnosis of primary headaches: results of a survey on patients attending headache centres.

Underdiagnosis of primary headaches was evaluated in 504 patients attending six Headache Centres in Lombardy. We found high figures of missed diagnoses (no diagnosis of a specific headache form), and of misdiagnosis (non-concordance between previous diagnoses made by the GP and the final diagnoses given by the headache specialist). We note that underdiagnosis in headache patients may have negative consequences, enhancing the risk of progressive worsening of primary headache syndromes, increasing their impact on individuals and on society, and favouring medication overuse.

A woman with abdominal pain and headache.

We describe a case of a 27-year-old woman who came to the Emergency Department presenting severe abdominal pain. She was evaluated by a gynaecologist and submitted to pelvic ecography without finding relevant alterations. In the successive hours, she presented severe headache in occipital region and in the posterior neck, poorly responsive to analgesic drugs. A cerebral CT scan was performed and was normal, and the patient came to our Department of Neurology. The neurological examination on admission was normal. This woman had a 7 years of long-lasting history of headache, diagnosed in another hospital as migraine without aura, and she referred a recent and progressive worsening of both the frequency and the severity of the headache. In the suspect of subarachnoidal haemorrhage, a lumbar puncture was performed, and was negative for bleeding, showing only a mild increase in the number of cells (12 leucocytes). Following the lumbar puncture, the patient presented a dramatic improvement of the headache. In the successive days, she lamented sellar hypoesthesia and, when asked, she referred a recent history of urinary and faecal retention. She was, therefore, submitted to an NMR of the lumbar and sacral medulla with evidence of a voluminous extradural formation in the sacral region suggestive for extradural sacral meningeal cyst. She was finally dispatched to the Department of Neurosurgery for surgical asportation of the cyst.

The role of the clinician in interpreting conventional neuroimaging findings in migraine patients.

Changes in cerebral white matter at CT or MRI have been reported in patients with migraine, especially in those with migraine with aura. Similar pictures may be present in asymptomatic subjects, and their nature is not completely understood, but their infarct-like nature is strongly suggested. Clinicians play an important role in the evaluation of those migraine patients in whom these nonspecific abnormalities are present. We suggest ruling out specific syndromes in which migraine attacks are associated with white matter changes (CADASIL, MELAS, multiple sclerosis and central nervous system vasculitis), as well as evaluating the presence of different vascular risk factors (genetic prothrombotic factors, patent foramen ovale, use of oral contraceptives, etc.). Their possible causative role in MRI lesions and in enhancing the risk of a negative clinical evolution must be considered in each individual case.

Headache and anxiety-depressive disorder comorbidity: the HADAS study.

Psychiatric comorbidity (prevalence and types) was tested in a naturalistic sample of adult patients with pure migraine without aura, and in two control groups of patients, one experiencing pure tension-type headache and the other combined migraine and tension-type headaches. The study population included 374 patients (158, 110 and 106) from nine Italian secondary and tertiary centres. Psychiatric comorbidity was recorded through structured interview and also screened with the Mini International Neuropsychiatry Interview (MINI). Only anxiety and depression were investigated. Psychiatric disorders were reported by 49 patients (14.6%; 10.9% of patients with migraine, 12.8% of those with tension-type headache and 21.4% of those with combined migraine and tension-type headaches). The MINI interview detected a depressive episode in 59.9% of patients with migraine, 68.3% of patients with tension-type headache and 69.6% of patients with combined migraine and tension-type headaches. Depression subtypes were significantly different across groups (p=0.03). Anxiety (mostly generalised) was reported by 18.4% of patients with migraine, 19.3% of patients with tension-type headache, and 18.4% of patients with combined migraine and tension-type headaches. The values for panic disturbance were 12.7, 5.5 and 14.2, and those for obsessive-compulsive disorders were 2.3, 1.1 and 9.4% (p=0.009). Based on these results, psychopathology of primary headache can be a reflection of the burden of the disease rather than a hallmark of a specific headache category.

Treatment strategies in the acute therapy of migraine: stratified care and early intervention.

Various treatment strategies have been proposed to help clinicians provide the most effective acute treatment for migraine patients. Stratified care is based on the concept that the most appropriate initial treatment can be prescribed after evaluation of each patient's headache characteristics. The results of a large multicentre trial showed that when patients were stratified according to disability grade, clinical outcomes were significantly better than with step-care approaches. Prospective studies have shown that treating migraines with triptans when pain is mild (early intervention) considerably increases success rates for endpoints (pain-free at 2 h, sustained pain-free state) for which triptans had relatively poor efficacy in pivotal trials, and which contribute most to patient satisfaction. Stratified care and early treatment are also cost-effective. However these strategies are not suitable for all patients. Stratified care may be rendered difficult by medication contraindications and changes in attack characteristics over time. Early triptan intervention carries a risk of medication overuse and might not be indicated in patients with lack of pain progression. Successful implementation of both strategies requires that physicians are well informed, and that they elicit an exhaustive headache history from each patient.

Early triptan intervention in migraine: an overview.

Although triptans are highly effective for the acute treatment of migraine, sustained pain-free rates--considered the optimal end-point--are in the range of 18%-27% for all triptans in clinical trials. A recently proposed strategy for treating migraine attacks is that triptans should be given early, when the pain is mild, rather than moderate or severe. Studies with different triptans have shown that early intervention can result in higher pain-free rates, together with reductions in rescue medication use and recurrence rates. However these studies suffer from methodological pitfalls: most were retrospective analyses of trials not designed to evaluate the benefit of early intervention; the definition of "early" differed from study to study; and placebo effects were not correctly evaluated. Furthermore, the disadvantages of this strategy in clinical practice, particularly the risk of medication overuse, have not been evaluated. We propose that only patients with particularly severe migraines and in whom attacks are always characterised by rapid progression of pain and other symptoms, should be advised to take a triptan as early as possible.

Topiramate in migraine prophylaxis.

This paper reviews results of placebo-controlled trials on topiramate (TPM) prophylaxis in migraine patients, and discusses issues regarding the use of this medication in clinical practice. Data from well conducted double-blind controlled trials and from a comparative trial show that TPM is effective against migraine, confirming the experience of physicians in various countries. Lack of major contraindications, high responder rate, good tolerability at the target dose (100 mg/day) following slow titration, and lack of weight gain make TPM one of the most effective and well accepted drugs for migraine prophylaxis.

Naratriptan in the short-term prophylaxis of pure menstrual migraine.

Menstrual migraines are particularly difficult-totreat. Few studies on the use of triptans in short-term prophylaxis of menstrually related migraine have been recently conducted, but evidences of triptans' efficacy in the specific case of pure menstrual migraine (PMM) are lacking. The aim of this study is to explore the efficacy and tolerability of naratriptan as short-term prophylaxis of pure menstrual migraine (PMM) attacks. A multi-centre, open, non comparative, pilot six-month study was conducted in women, aged 18 years or older, with regular menstrual cycles and with a history of migraine without aura exclusively associated to the perimenstrual period. After an observation period of three months, patients took for three consecutive menstrual cycles oral naratriptan 1 mg twice daily, starting two days before the expected onset of menstruation and continuing for six days. Ninety-eight women with a history of PMM were screened for study participation, and 61 entered the study. Fifty-nine comprised the intent-to-treat population. The mean number of PMM attacks decreased from 3.5+/-1.4 in the 3-month observation period to 1.6+/-1.3 in the 3-month treatment with naratriptan. The pecentage of responders (subjects who recorded a decrease-equal or more than 50%-in the mean number of attacks) was 61.4%. A tendency towards a decrease in headache severity and in the presence of associated symptoms was observed during treatment. At least one adverse event during the treatment period was reported by 19 patients (31.1%). No serious adverse events occurred. Naratriptan may be an effective and safe treatment option in the short-prophylaxis of PMM.

Coagulation abnormalities in migraine and ischaemic cerebrovascular disease: a link between migraine and ischaemic stroke?

Migraine, particularly migraine with aura, is a risk factor for ischaemic stroke. The mechanisms underlying this association are obscure. One hypothesis is that shared risk factors may be the cause of this association. Over the last decade, studies have suggested an association between migraine and genetic abnormalities in coagulation factors which play an important role in stroke pathogenesis. Although the results of studies on various prothrombotic conditions are conflicting, findings suggest a higher frequency of some genetic abnormalities in migraine with aura patients. Thus, persistent hypercoagulability may explain the tendency for these patients to develop thromboembolic cerebrovascular events, especially when they are exposed to additional procoagulant stresses. Further studies on larger samples are required to test this hypothesis.

Neurobiology of chronic migraine.

Chronic daily headache (CDH) is an important problem for clinicians. It is frequent in tertiary care structures, although at present there is no clear consensus about definitions and operational criteria. In fact, CDH is a group of headache disorders that includes chronic migraine (CM). CDH usually evolves from an episodic headache form, which was migraine in most cases. Several psychopathological factors (e.g. psychiatric comorbidity, personality traits or stressful life events) and some somatic disorders (e.g. like arterial hypertension, allergic condition, sleep disturbances) are frequent in CM patients. Caffeine consumption, alcohol overuse and medication overuse (abortive drugs for migraine) could favour chronicity. The possible role of these factors remains poorly understood. Prospective studies and research about the pathophysiology of chronic pain will lead to a better understanding of CM.

Electromyographic biofeedback-assisted relaxation training in juvenile episodic tension-type headache: clinical outcome at three-year follow-up.

Although tension-type headaches are more common than migraine in children and adolescents, the limited studies that have been conducted with juveniles have focused chiefly on migraine treatment and its course. This report describes the clinical benefits for an electromyographic biofeedback-assisted relaxation treatment program for a group of children and adolescents experiencing episodic tension-type headache and examines whether the clinical presentation changed for headaches that remained. Of the 54 consecutive juveniles who began treatment, 38 completed and were available to participate in the 3-year follow-up. Headaches improved measurably immediately following treatment, with further gains being evident through 3 years. The few headaches that did occur at 3 years were nearly identical symptom-for-symptom to those that were experienced prior to treatment. This report suggests that behavioural treatment is a viable and durable intervention for juvenile episodic tension-type headache, but more definitive claims cannot be made due to the uncontrolled nature of the study. Further investigation is warranted.

Verapamil in the prophylaxis of episodic cluster headache: a double-blind study versus placebo.

The authors performed a double-blind, double-dummy study to compare the efficacy of verapamil with placebo in the prophylaxis of episodic cluster headache. After 5 days' run-in, 15 patients received verapamil (120 mg tid) and 15 received placebo (tid) for 14 days. The authors found a significant reduction in attack frequency and abortive agents consumption in the verapamil group. Side effects were mild. These findings provide objective evidence for the effectiveness of verapamil in episodic cluster headache prophylaxis.

Abnormal 24-hour urinary excretory pattern of 6-sulphatoxymelatonin in both phases of cluster headache.

The typical cyclic occurrence of cluster headache suggests the involvement of hypothalamic rhythm regulating centers in the pathogenesis of this primary headache. In previous studies, reduced 24-h plasma melatonin levels during the cluster period, loss of circadian melatonin secretion in remission, as well as permanently reduced excretion of urinary melatonin in both illness phases have been reported, supporting the hypothesis of a hypothalamic derangement. In this study, the 24-h urinary excretion of the main melatonin metabolite, 6-sulphatoxymelatonin, was evaluated in 20 cluster period cluster headache patients. Thirteen were retested 12 months later, in the same period of the year, during remission. Fourteen age- and sex-matched healthy subjects were the controls. As expected, significantly higher levels of 6-sulphatoxymelatonin were present in nocturnal urine than in day-time urine in controls, while in both cluster headache groups urinary levels of this metabolite did not differ between day and night. Nocturnal levels of 6-sulphatoxymelatonin were significantly lower in both cluster headache groups than controls. Day-time levels did not differ significantly between the groups. Altered excretion of urinary 6-sulphatoxymelatonin even during remission indicates that at least some of these anomalies are independent of the pain, and provides further evidence of involvement of the hypothalamic rhythm regulating centers in cluster headache.