'INDOTEST' in atypical hemicrania continua.

Hemicrania continua (HC) is an indomethacin-responsive headache characterized by a chronic, strictly unilateral, side-locked without side-shifting, persistent headache. We report three cases of HC with atypical features in which an acute administration of indomethacin 50 mg IM (INDOTEST) was performed. In all three cases INDOTEST predicted chronic responsiveness to indomethacin. Thus, in cases of HC with atypical features, INDOTEST could help for a correct diagnosis and therapy.

A case of sarcoidosis presenting as a non-specific intramedullary lesion.

Neurosarcoidosis occurs in 5-15% of sarcoidosis cases. Approximately 50% of patients with neurosarcoidosis present with a neurological disease at the time sarcoidosis is first diagnosed. Spinal sarcoidosis is rare. We report the case of a 61-year-old man with a highly aspecific intramedullary lesion as the first manifestation of sarcoidosis. One year after the onset of neurological symptoms, the high levels of angiotensin-converting enzyme and the results of a total body gallium scan and bronchoalveolar lavage supported the diagnosis of sarcoidosis. Isolated single reports indicate that spinal neurosarcoidosis may be the initial manifestation of sarcoidosis. In our case, magnetic resonance imaging of the dorsal spine showed a largely aspecific lesion. Neurosarcoidosis should be considered in the differential diagnosis of intramedullary cord lesion with leptomeningeal enhancement; a systematic search for evidence of sarcoidosis should be mandatory in all cases for a correct diagnosis and early treatment.

Environmental factors and Parkinson's disease: a case-control study in the Tuscany region of Italy.

To date the aetiology of Parkinson's disease (PD) is unknown although both genetic susceptibility and environmental factors appear to play an important role in the development of the disease. Recent data have also indicated that chronic exposure to a common pesticide can reproduce the neurochemical, behavioral and neuropathological features of PD. The epidemiological studies previously carried on the prevalence of PD in population exposed to environmental factors have produced controversial results, probably because of different trial design and different analysis methods. A case-control retrospective study was conducted in a well-defined geographic area in Tuscany-Italy with the aim to identify environmental factors possibly related to PD. No significant difference between PD patients and control subjects was observed in time spent in rural or industrial residence, in well water drinking and in the exposure to herbicides and pesticides. A significant difference between patients with PD and controls was reported for cigarette smoking, controls resulting more likely cigarette smokers in comparison with PD patients. The present findings support the view of a protective effect of cigarette smoking and do not show any significant association between environmental factors and the risk of development of PD.

Psychiatric comorbidity in a population of Parkinson's disease patients.

Behavioural disturbances are frequently observed in Parkinson's disease (PD), including mood and anxiety disorders. The existence of a comorbidity between such psychiatric disorders in PD patients has been suggested only in a few studies. To assess the prevalence of mood and anxiety disturbances, and the rate of comorbidity of such disorders in PD. Secondary aim was to correlate the prevalence of psychiatric disorders in PD with age, sex, laterality of motor symptomatology, clinical features, severity of disease, age of onset and PD duration, and anti-parkinsonian therapy. Ninety consecutive PD outpatients, and 90 age- and sex-matched controls were included. All PD patients enrolled were non-fluctuating (21 de novo, 69 treated with levodopa or dopamine agonists). PD patients and controls with Mini Mental State Examination score <23 were excluded. Psychiatric diagnosis was performed by semistructured interview according with DSM-IV criteria and the severity of depressive and anxious symptoms was rated with clinical rating scales. Major depression was found in 21.1% PD patients vs. 3.3% controls (P < 0.01, chi-square analysis), dystimia in 18.8% PD patients vs. 4.4% controls (P < 0.05), panic disorders in 30% PD patients vs. 5.5% controls (P < 0.01). No difference in the prevalence of other anxiety disorders was observed between the two groups. The comorbidity of mood and anxiety disorders was found in 19.3% PD patients vs. 8.6% controls (P < 0.01). No correlation was reported between the prevalence of behavioural disturbances and any of the demographic, clinical or pharmacological data taken into account. Our findings might suggest the existence of a wide spectrum of psychiatric disorders in PD ranging from pure depressive disorders, comorbid depressive and anxiety disorders, and pure anxiety disorders, presumably linked to the same neurobiological substrate.

Contribution of cerebellum and brainstem in the control of eye movement: evidence from a functional study in a clinical model.

The idiopathic cerebellar ataxias (IDCA) comprise a wide spectrum of neurodegenerative diseases with heterogeneous neuropathology, characterized by the negativity of search for any known genetic mutation. On the basis of both their clinical presentation and their magnetic resonance imaging pattern, patients with IDCA can be subdivided into patients with a purely cerebellar syndrome and atrophy of the cerebellum (IDCA-C) and patients with additional noncerebellar symptoms and atrophy of both cerebellum and brainstem (IDCA-P). The aim of the present study was to evaluate the disaggregated contribution of brainstem and cerebellum in the control of eye movements, by means of an extensive battery of quantitative tests covering most oculomotor subfunctions related to lesions of the cerebellum and the brainstem. The smooth-pursuit movement analysis showed a decrease in gain and magnitude in both subgroups of IDCA with respect to normal controls, without any significant differences in the prevalence pattern between the two subgroups; the mean values of these parameters, however, were significantly lower in IDCA-P than in IDCA-C subjects in both gain (P < 0.01) and magnitude (P < 0.001). No statistically significant difference was observed between the two subgroups in the analysis of saccadic movements or in the other parameters investigated. The distinction between IDCA-P and IDCA-C subgroups has clinical implications, as a poorer prognosis is related to brainstem involvement, which may occur late in the course of the disease. Thus, the possibility to detect the brainstem involvement, also in association with cerebellar impairment, by a relatively simple eye-movement analysis, potentially useful mainly in follow-up investigations, needs to be evaluated further.

SSRIs do not worsen Parkinson's disease: evidence from an open-label, prospective study.

Selective serotonin reuptake inhibitors (SSRIs) have been reported to be useful in the treatment of depression in patients with Parkinson's disease (PD). However, a few reports have suggested that SSRIs may worsen parkinsonian motor symptomatology and extrapyramidal side effects have been reported in depressed patients treated with SSRIs. So far, no prospective trial comparing the effects of different SSRIs in depressed patients with PD has been performed. The aim of the present study was to assess the effects of four SSRIs (citalopram, fluoxetine, fluvoxamine, and sertraline) on motor performance and their efficacy on depression in a group of patients with PD. Sixty-two consecutive nondemented, nonfluctuating, depressed patients with PD were included in four treatment groups (15 patiens received citalopram, 16 fluoxetine, 16 fluvoxamine, and 15 sertraline). The evaluation of extrapyramidal and depressive symptomatology was performed with use of the Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory, and Hamilton Depression Rating Scale at baseline and after 1, 3, and 6 months. Fifty-two patients completed the study. UPDRS scores were not significantly modified by the add-on therapy with each of the SSRIs studied. A significant improvement in depressive symptoms from baseline to the end of the trial was obtained with all SSRIs (Beck and Hamilton scores improving; p < 0.05 according to an analysis of variance). Our findings suggest that SSRIs do not significantly worsen extrapyramidal symptomatology and may ameliorate depression in patients with PD.

Paroxetine in Parkinson's disease: effects on motor and depressive symptoms.

Selective serotonin reuptake inhibitors have been used in the treatment of depression in patients with PD. Conflicting data as to whether selective serotonin reuptake inhibitors worsen parkinsonian motor symptomatology have been reported. In this study, the additional 6 months therapy with paroxetine 20 mg/d in a group of depressed patients with PD did not modify parkinsonian motor function (Unified Parkinson's Disease Rating Scale scores); however, in one patient, fully reversible worsening of tremor was observed. Depression, as evaluated by Beck Depression Inventory and Hamilton Depression Rating Scale, improved from baseline to final visit (p < 0.05 by analysis of variance).

Mexiletine in the treatment of torticollis and generalized dystonia.

Mexiletine is an antiarrhythmic drug that has been reported to exert antidystonic properties. We performed an open-label study to collect further evidence of the antidystonic effect of mexiletine in spasmodic torticollis (ST) and to evaluate its possible use in generalized dystonia. We administered mexiletine to six patients with dystonia (three with generalized dystonia and three with ST) who had failed to respond to previous pharmacotherapy. The drug was started at a dose of 200 mg/d by mouth and increased up to a maximum dose of 800 mg/d. Patients were evaluated at regular intervals over a 6-week period with use of the Fahn & Marsden Dystonia Scale and the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and videotaped. At the end of the trial, the videotapes were reviewed and scored by a blind observer. Patients were then followed for at least 1 year and evaluated every 3 months at the dose reached during the study period. No adverse effects were reported in five patients; in one patient, dizziness developed at the dosage of 800 mg/d, requiring a reduction of the dose. At the end of a 6-week period, a significant improvement in the rating scale for dystonia and in videotape ratings was observed after mexiletine treatment (p < 0.01). Our data indicate that mexiletine is a useful drug in dystonia treatment.

Prevalence of headache syndromes in panic disorder.

We investigated the prevalence of headache in a group of patients attending a psychiatric clinic because suffering from panic disorder, according to DSM-IV criteria. The psychopathological assessment was performed with the 'Panic Disorder/Agoraphobia Questionnaire' and the presence of headache was evaluated according to the criteria of the International Headache Society. The results showed that two-thirds of patients met the criteria for a diagnosis of headache, with migraine without aura being the most frequent form, followed by tension headache, while two patients only were affected by migraine with aura. When we compared panic patients with and without headache, those with headache had a longer duration of panic disorder, a higher number of attacks and a heavier family loading for panic disorder and headache. This suggests that the comorbidity of headache with panic disorder renders this condition more severe and possibly responsive to different treatments compared to panic disorder alone.

Psychiatric comorbidity and psychosocial stress in patients with tension-type headache from headache centers in Italy. The Italian Collaborative Group for the Study of Psychopathological Factors in Primary Headaches.

A multicenter study was carried out in 10 Italian Headache Centers to investigate the prevalence of psychosocial stress and psychiatric disorders listed by the IHS classification as the "most likely causative factors" of tension-type headache (TTH). Two hundred and seventeen TTH adult outpatients consecutively recruited underwent a structured psychiatric interview (CIDI-c). The assessment of psychosocial stress events was carried out using an ad hoc questionnaire. The psychiatric disorders that we included in the three psychiatric items of the fourth digit of the IHS classification were depressive disorders for the item depression, anxiety disorders for the item anxiety, and somatoform disorders for the item headache as a delusion or an idea. Diagnoses were made according to DSM-III-R criteria. At least one psychosocial stress event or a psychiatric disorder was detected in 84.8% of the patients. Prevalence of psychiatric comorbidity was 52.5% for anxiety, 36.4% for depression, and 21.7% for headache as a delusion or an idea. Psychosocial stress was found in 29.5% of the patients and did not differ between patients with and without psychiatric comorbidity. Generalized anxiety disorder (83.3%) and dysthymia (45.6%) were the most frequent disorders within their respective psychiatric group. The high prevalence of psychiatric disorders observed in this wide sample of patients emphasizes the need for a systematic investigation of psychiatric comorbidity aimed at a more comprehensive and appropriate clinical management of TTH patients.

Flunarizine in migraine prophylaxis: predictive factors for a positive response.

The efficacy of flunarizine in migraine prophylaxis is confirmed in both open and controlled trials. However, it is unknown what factors may influence a good response to prophylaxis with flunarizine. The aim of this study was to determine the possible predictive factors for therapeutic responsiveness to 3 months' treatment with flunarizine. One-hundred headache patients treated with flunarizine were evaluated. We considered "responders" those patients who recorded a reduction in migraine frequency of 75% after treatment. Statistical analysis revealed four factors which might influence therapeutic responsiveness in our patients. Positive factors were a family history (p<0.01) and high intensity of pain (p<0.01); negative factors were frequent attacks (p<0.01) and a history of analgesic abuse (p<0.001). Patients with no previous history of analgesic abuse, low frequency of attacks at baseline, higher levels of migraine pain, and positive family history constitute the prototype of flunarizine long-term treatment responders.

Phantom eye: features and prevalence. The predisposing role of headache.

We prospectively evaluated the frequency, time-course and predisposing factors of phantom eye syndrome in 53 patients who underwent surgical eye amputation to cure ocular cancer. Before surgery, patients were classified as Group I (n = 25) if they had no history of headache or Group II (n = 28) if they were headache sufferers. Three clinical patterns were distinguished: phantom pain, non-painful phantom phenomena and photopsias. Their symptoms developed 7 days to 6 months after surgery, with peak incidence after 6 months (photopsia 43%; phantom pain 28%; non-painful phantom phenomena 62%). Phantom eye syndrome was more common in headache sufferers than in non-headache subjects. Headache sufferers were more prone to phantom pain, but more so to non-painful phenomena and photopsias. These findings are in accord with our previous results indicating that primary headache sufferers are prone to phantom tooth pain.

Long-term follow-up after flunarizine or nimodipine discontinuation in migraine patients.

Various open and controlled studies have confirmed the antimigraine action of flunarizine, while the antimigraine properties of nimodipine are still open to controversy. Moreover, only a few studies include an additional follow-up after discontinuation of migraine prophylaxis with either drug. We carried out a single blind evaluation of the efficacy and tolerance of flunarizine (25 patients) in comparison with nimodipine (25 patients) and the long-term effect after discontinuation of a 6-month treatment. Both medications significantly reduced migraine frequently and severity. Flunarizine was more efficacious than nimodipine in reducing migraine frequency (p < 0.001), pain severity (p < 0.05), migraine index (p < 0.05) and corrected migraine index (p < 0.05). The positive effect lasted 8.4 +/- 4.0 months after discontinuation of flunarizine and 4.9 +/- 3.5 months after nimodipine (p < 0.05). Our results suggest that flunarizine is more effective than nimodipine in the prophylactic treatment of migraine. The positive effect after drug discontinuation lasts longer with flunarizine, compared to nimodipine.

Amitriptyline and dexamethasone combined treatment in drug-induced headache.

Frequent or regular intake of antimigraine drugs, including analgesics, constitutes a common cause of chronic daily headache. Discontinuation of symptomatic medication can produce an increase in head pain accompanied by withdrawal symptoms. We report the favourable outcome of treating a group of outpatients with the combination of amitriptyline, dexamethasone and sumatriptan. Dexamethasone (4 mg/day) was given intramuscularly for 2 weeks, amitriptyline orally at night (50 mg/day) for at least 6 months, and sumatriptan subcutaneously to treat acute headache attacks. Eighteen out of 20 patients abstained from drug abuse. Eleven of these 18 patients showed a marked reduction in headache frequency (at least 75% in relation to the basal value), and were considered "very good responders". The other seven patients experienced at least 50% reduction in headache frequency compared to baseline. This preliminary report suggests that drug-induced headache can be treated effectively in outpatients using dexamethasone, amitriptyline and sumatriptan in combination with significant benefit in everyday life conditions.

Headache, panic disorder and depression: comorbidity or a spectrum?

Past epidemiological and clinical research has identified depression as the most common psychiatric disorder associated with headache. The present study carried out in a neurology headache clinic showed that the major associations were with current anxiety disorders, especially panic and related conditions. These findings were particularly true of the subgroup of migraine with aura; in the relatively few patients with mood disorders, depression was nearly always comorbid with panic or other anxiety disorders. Past history of depression was mainly a characteristic of the tension headache group. These data are compatible with the hypothesis that migraine, especially that with aura, panic disorder and some forms of depressive illness are part of the same spectrum.

White matter MRI hyperintensities in a hundred and twenty-nine consecutive migraine patients.

The most frequently reported abnormal MRI finding in migraine is the presence of high signal white matter foci (WMF) on long TR images. Recently, WMF have been distinguished in periventricular WMF (PVF), when contiguous to ventricles, and deep WMF (DF), when far from these. DF, but not PVF, appear positively correlated with cerebrovascular risk factors and are called leukoaraiosis. In this study the MRI examination was performed in 129 consecutive migraine patients (83 of them had migraine without aura and 46 migraine with aura). In 19.3% of the migraineurs studied we observed WMF on T2 weighted images strictly localized in the deep white matter (DF). No PVF were observed. These findings were independent of the type of migraine and did not correlate with age, sex, disease duration, or frequency of attacks. The presence in a subgroup of migraineurs of leukoaraiosis (DF), for which a vascular genesis has been hypothesized, suggests that migraine could represent, a cerebrovascular risk factor in these patients.

Platelet 3H-imipramine binding and sulphotransferase activity in primary headache.

We investigated platelet 3H-imipramine (3H-IMI) binding, a putative peripheral serotonergic marker, and the activity of sulphotransferase (ST), an enzyme involved in the catabolism of catecholamines and phenolic compounds, in 14 patients suffering from migraine without aura (MWoA) and in 10 with tension-type headache (TH), as compared with a group of controls. The possible relationships between the biological parameters and clinical features were also examined. The results showed that the two groups of patients had a lower number of 3H-IMI binding sites and a lower activity of the thermolabile form of ST, which acts preferentially on monoamine substrates, than the healthy controls, with no intergroup differences. Significant correlations between psychopathological rating scales and characteristics of the illness were observed in the patients with TH. The decreased number of platelet 3H-IMI binding sites is suggestive of a presynaptic serotonergic dysfunction and confirms the involvement of 5HT in primary headaches. The reduced ST activity might produce changes in the level of sulphated biogenic amines, including dopamine and tyramine, which might have an additional role in the pathophysiology of some aspects of primary headache.