N Pavese

Intravenous amantadine improves levadopa-induced dyskinesias: an acute double-blind placebo-controlled study.

Experimental evidence suggests that glutamatergic receptor blockade may improve the motor response complications associated with long‐term levodopa treatment in Parkinsons disease (PD) patients. Our objective was to evaluate the acute effect of amantadine, a noncompetitive antagonist of the N‐methyl‐D‐aspartate (NMDA) receptor, on levodopa‐induced dyskinesias, and to gain further insights into the antidyskinetic mechanism of this drug. Nine PD patients with motor fluctuations and severely disabling peak of dose dyskinesias received their first morning levodopa dose, followed by a 2‐hour intravenous amantadine (200 mg) or placebo infusion, on two different days. Parkinsonian symptoms and dyskinesias were assessed every 15 minutes during the infusion and for 3 hours thereafter, while patients were taking their usual oral antiparkinsonian therapy, by means of Unified Parkinsons Disease Rating Scale (UPDRS, motor examination), tapping test, and a modified Abnormal Involuntary Movement Scale (AIMS). Intravenous amantadine acutely improved levodopa‐induced dyskinesias by 50%without any loss of the anti‐parkinsonian benefit from levodopa. This study confirms the antidyskinetic effect of amantadine and strengthens the rationale for using antiglutamatergic drugs in the treatment of parkinsonian motor fluctuations.

Spontaneous and induced aneuploidy in peripheral blood lymphocytes of patients with Alzheimer's disease

Abstract This study was aimed at assessing whether peripheral blood lymphocytes of patients with Alzheimer’s disease (AD) show significant levels of aneuploidy and high percentages of cytogenetic events in vitro, indicating a predisposition to aneuploidy spontaneously, or after chemical treatment in vitro. A group of affected individuals and a group of unaffected, age-, sex- and smoking-habit-matched controls were identified. Lymphocytes were cultured for analysis of the following cytogenetic parameters: premature centromere division (PCD), satellite associations of acrocentric chromosomes (SA) and micronuclei (MN). In a subset of subjects, the fluorescence in situ hybridization (FISH) technique was combined with the MN assay, by means of a pancentromeric DNA probe for the detection of the presence of centric material. To evaluate the sensitivity to aneuploidogenic agents, in vitro treatment of lymphocytes of affected individuals was performed by adding griseofulvin, a chemical whose supposed target is microtubule-associated protein(s). Both the spontaneous frequency of MN and the frequency of PCD was significantly higher in patient cells than in controls. Furthermore, after application of the FISH technique, we found that the majority of MN were composed of whole chromosomes (because of the phenomenon of chromosome loss). Metaphase analysis for the detection of associative events between satellite regions of acrocentric chromosomes showed no differences between the two groups under study. Analysis of sensitivity to the aneuploidogen griseofulvin showed that the patient group was characterized by lower levels of MN induction compared with controls. Our data confirm that peripheral blood lymphocytes of AD patients are prone to undergo aneuploidy spontaneously in vitro and support the hypothesis that microtubule impairment might be associated with the disease.

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.

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.

Clinical outcome and magnetic resonance imaging of carbon monoxide intoxication. A long-term follow-up study.

Abstract The clinical and neuroradiological outcome of carbon monoxide (CO) intoxication was evaluated prospectively in 30 patients over a follow-up period of 3 years. Among the patients studied, 22 had been acutely exposed to CO while 8 were chronically exposed.One month after CO poisoning, 12 of the 22 patients with acute intoxication showed magnetic resonance imaging (MRI) abnormalities: 6 also had neurological sequelae and 6 were asymptomatic. The remaining 10 patients showed neither MRI abnormalities nor neurological sequelae. During the 3-year follow-up, 4 of the patients with both MRI abnormalities and neurological sequelae improved in both clinical features and MRI findings. One of the 6 asymptomatic patients with MRI abnormalities developed a progressive cognitive impairment 2 months after acute intoxication, with a concomitant severe worsening of the MRI lesions. Among the 10 patients with neither MRI abnormalities nor neurological sequelae, only 1 developed neurological sequelae after a clear period of 4 months.In the group of patients who experienced chronic CO intoxication, only 1 presented with a neuropsychiatric syndrome which improved at follow-up. Brain MRI showed white matter lesions which remained unchanged at control scan after 1 year.In conclusion, we observed that some patients with severe CO poisoning and neurological sequelae may fully regain normal functions after approximately 1 year. The presence of MRI lesions 1 month after CO poisoning did not accurately predict the subsequent outcome. The observation of a clear period longer than the usual 2–40 day interval in 2 patients should be considered for careful planning of follow-up and for prognosis in CO-poisoned patients.

The relation between EMG activity and kinematic parameters strongly supports a role of the action tremor in parkinsonian bradykinesia

The kinematics characteristics of an upper arm extension of large amplitude (90°) performed in the horizontal plane and the simultaneous activity of the shoulder muscles were recorded in 12 parkinsonian patients and in six normal control subjects. The movement, triggered by an acoustic “go” signal, was preceded by an isometric adduction.

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.

Transcranial Doppler Ultrasound in Migraine and Tension-Type Headache After Apomorphine Administration: Double-Blind Crossover Versus Placebo Study

The effect of the dopaminergic agonist apomorphine on blood velocity in the middle cerebral artery has been studied in patients with migraine, tension-type headaches, and healthy subjects by means of transcranial Doppler monitoring. Following the administration of apomorphine, systolic velocity and mean velocity significantly increased and pulsatility index significantly decreased in migraineurs compared to placebo and to the other groups of subjects. These changes were dose-dependent and showed a time-curve compatible with the pharmacokinetic profile of the drug. The different effect of apomorphine in migraineurs compared with controls and tension-type headache patients implies that migraineurs have increased sensitivity to dopaminergic stimuli and suggests that transcranial Doppler monitoring after apomorphine administration could be a useful tool in the evaluation of migraineurs.

Thyroid function and autoimmunity in Parkinson's disease: a study of 101 patients

Thyroid disease is the endocrine dysfunction most frequently reported in association with idiopathic Parkinsons disease (PD). The aim of this study was to assess thyroid autoimmunity and function in PD, and to verify the effect of long term l-dopa and/or dopamine therapy on thyroid function. We studied 101 consecutive PD outpatients and seventy age- and sex-matched neurological non-PD patients as controls. They were evaluated for free thyroid hormones, TSH and thyroid autoantibodies. No significant difference in the prevalence of thyroid autoimmunity and dysfunction was found between PD patients and neurological controls (10.8% in PD patients vs 10% in neurological controls). Further, treatment with l-dopa and/or dopaminergic drugs and the stage of Parkinsons disease did not affect thyroid function. In conclusion, the prevalence of thyroid autoimmunity in PD patients appeared similar to that as described in the general population, though thyroid dysfunction was observed in over than 10% of PD patients. Indeed, neurologists should be alerted to the possible complications arising from thyroid dysfunction in Parkinsons disease, but thyroid function tests should be performed only when justified on clinical grounds.

Valproate-withdrawal induced migraine

After preliminary studies showing that sodium valproate (VPA) is effective in migraine prophylaxis1 and in the treatment of chronic daily headache,2 Hering and Kuritzky3 have recently completed a double-blind, randomized, crossover trial in 29 migraineurs which indicated that VPA 400 mg taken twice a day was more effective than placebo in reducing the number and the severity of migraine attacks. Even though further studies are essential for testing the real efficiency of VPA in migraine, the experience for many clinicians currently using the drug is very positive.