Piero Barbanti

Unilateral Cranial Autonomic Symptoms in Migraine

Unilateral cranial autonomic symptoms (UAs) such as lacrimation, conjunctival injection, eyelid oedema and nasal congestion, which are the hallmark of trigeminal autonomic cephalgias, may also occur in an as yet undetermined proportion of migraine patients. We studied 177 consecutive migraineurs to assess the frequency of UAs and the clinical characteristics of such patients. UAs were reported by 81 patients (45.8%), ocular symptoms alone or in combination with nasal symptoms being the most frequent. The headache was more severe (P< 0.0002) and more strictly unilateral (P< 0.0004) in patients who reported UAs than in those without. Thus, the presence of UAs suggests an activation of the trigeminal-autonomic reflex, probably related to an over-activation of the trigeminal afferent arm. These findings could have therapeutic implications, given the potential large-scale recruitment of peripheral neurovascular 5-HT1B/1D receptors (the target of acute migraine treatment) in such patients.

BI 44370 TA, an oral CGRP antagonist for the treatment of acute migraine attacks: results from a phase II study.

Methods: Four hundred and sixty-one adult subjects with migraine were randomised to one of five treatments, the oral antagonist at the calcitonin gene-related peptide (CGRP) receptor BI 44370 TA (50 mg, 200 mg, 400 mg), active comparator eletriptan 40 mg or placebo. The analysis included 341 subjects who took study medication. Results: The primary endpoint, pain-free after two hours, was reached by significantly more subjects in the BI 44370 TA 400 mg (20/73 = 27.4%) and eletriptan 40 mg (24/69 = 34.8%) groups compared to placebo (6/70 = 8.6%, p = .0016), but not by subjects in the BI 44370 TA 200 mg group (14/65 = 21.5%). The effect of 50 mg BI 44370 TA (5/64 = 7.8%) was similar to that of placebo. Analysis of secondary endpoints supported the conclusion from the primary analysis. The frequency of adverse events was low in all groups. Conclusion: Efficacy of BI 44370 TA was shown in a dose-dependent manner in the treatment of acute migraine attacks.

Donepezil in the treatment of hallucinations and delusions in Parkinson's disease.

As cholinergic mechanisms may be at least partially responsible for hallucinations and delusions in Parkinson’s disease (PD), we conducted an open study in 8 PD patients to assess the efficacy and tolerability of the cholinesterase inhibitor donepezil, 5 mg at bedtime for two months, in the treatment of these complications. Hallucinations and delusions improved significantly in all patients. Donezepil was overall well tolerated, but a deterioration in motor disability was noted in 2 out of 8 patients.

Excessive daytime sleepiness in de novo and treated Parkinson's disease

Excessive daytime sleepiness (EDS) in Parkinsons disease (PD) is due to either treatment‐related factors or the disease itself. The study of this disturbing phenomenon in de novo parkinsonian patients may contribute to a better understanding of its pathophysiology. We conducted a case control study in which we compared 25 PD patients who had never been treated before with dopaminergic drugs (de novo PD), 50 PD patients being treated with dopaminergic drugs (treated PD), and 25 healthy control subjects, all of whom were matched for age and gender. EDS was measured by means of the Epworth Sleepiness Scale (ESS) and quality of sleep by means of the Pittsburgh Sleep Quality Index (PSQI). ESS and PSQI scores were not statistically different between de novo PD patients and controls, whereas they were significantly higher in treated PD. Differences in ESS score variability were best explained by the treatment effect, whereas there was no clear correlation between PSQI and any of the clinical variables considered.

Increased expression of dopamine receptors on lymphocytes in Parkinson's disease

Dopamine D1‐like and D2‐like receptors on peripheral blood lymphocytes (PBL) were assayed in 50 de novo patients with idiopathic Parkinsons disease (PD), in 36 neurologic control subjects (multiple‐system atrophy, n = 16; essential tremor, n = 10; other neurodegenerative diseases, n = 10), and in 26 healthy control subjects by radioligand binding assay techniques using [3H]SCH 23390 and [3H]7OH‐DPAT as ligands. Patients with PD revealed a higher density (Bmax) of dopamine D1‐like (p <0.001) and D2‐like (p <0.00001) receptors on PBL than either neurologic or healthy control subjects, whereas no differences in Bmax were observed among patients affected by other neurologic diseases and healthy control subjects. The affinity (Kd) of both radioligands was similar in the groups investigated. The pharmacologic profile of [3H]SCH 23390 and [3H]7OH‐DPAT binding was consistent with the labeling of dopamine D5 and D3 receptor subtypes, respectively. Twenty‐five of the 50 patients with PD were retested after 3 months of therapy with levodopa or bromocriptine. Both treatments reduced the density of D1‐like (p <0.001) and D2‐like (p <0.001) receptors on PBL to values comparable to those of control subjects. The increased density of D1‐like and D2‐like receptors on PBL in de novo PD patients may represent an upregulation mechanism resulting from the diffuse impairment of the dopaminergic system in PD.

Donepezil in the treatment of progressive supranuclear palsy

Objectives– To evaluate the effect of 3 month therapy with donepezil, a centrally acting cholinesterase inhibitor, on cognitive performances, motor function and daily living activities in progressive supranuclear palsy (PSP). Materials and methods– Six patients with a diagnosis of PSP were evaluated at baseline and after 3 months of treatment with donepezil, 10 mg given at bedtime. Cognitive functions, motor symptoms and daily activities were evaluated by means of appropriate rating scales. Results– Donepezil was not effective on cognitive dysfunction and did not change ratings of daily living. Parkinsonian symptoms were unaffected by donepezil treatment. Conclusions– Cholinergic replacement therapy alone is not likely to improve symptoms in a disorder characterized by a more widespread impairment of monoaminergic systems. Larger studies may be necessary to confirm the lack of effect of donepezil in this disorder.

Migraine Patients Show an Increased Density of Dopamine D3 and D4 Receptors on Lymphocytes

Recent studies have revealed peculiar functional and genetic features of dopamine receptors in migraine. As peripheral blood lymphocytes (PBL) may represent a tool for peripheral detection of neuroreceptors, we compared the expression of dopamine D3 (DRD3) and D4 (DRD4) receptors on PBL in migraine patients and in healthy controls using radioligand binding assay techniques in the presence of antidopamine D2-like receptor antibodies. The dopamine D2-like receptor agonist [3H]7-OH-DPAT was used as a radioligand. An increased density of both DRD3 (P = 0.0006) and DRD4 (P = 0.002) on PBL was observed in migraineurs compared with controls. This up-regulation might reflect central and/or peripheral dopamine receptor hypersensitivity due to hypofunction of the dopaminergic system. These findings support the view that dopamine D2-like receptors are involved in the determination of the so-called migraine trait, which may help to elucidate several clinical features of the disease.

A case–control study on excessive daytime sleepiness in episodic migraine

Migraine patients often complain of sleepiness, a problem that manifests both during and outside an attack, may impair the quality of life and can lead to potentially harmful situations. Findings from an uncontrolled study suggest that a high percentage of migraineurs experience excessive daytime sleepiness (EDS). We investigated EDS in a case-control study on 100 patients with episodic migraine and 100 age- and sex-matched healthy controls and also assessed sleep quality, anxiety and depression. Although it was found that EDS was more frequent in migraineurs than in controls (14% vs. 5%; odds ratio 3.1; 95% confidence interval 1.1–8.9), the frequency was lower than previously reported. EDS correlated with migraine disability, sleep problems and anxiety. EDS in patients with migraine probably stems from the full constellation of headache-sleep-affective symptoms resulting from the complex clinical burden of the disease.

Amitriptyline Is Effective in Chronic But Not in Episodic Tension-Type Headache: Pathogenetic Implications

The tricyclic antidepressant amitriptyline, is an effective drug for the treatment of chronic tension‐type headache and for other chronic pain syndromes, but it is also effective in the prophylaxis of an episodic type of headache such as migraine. However, its efficacy in episodic tension‐type headache has not yet been clarified. We compared the efficacy of amitriptyline (25 mg/day) in 82 nondepressed patients with either chronic or episodic tension‐type headache in an open‐label study. Amitriptyline significantly reduced (P<0.05) frequency and duration of headache as well as analgesic consumption in chronic, but not in episodic, tension‐type headache. Further placebo‐controlled trials, possibly with higher doses of amitriptyline, might confirm if the different pattern of response to amitriptyline can be explained in terms of different involvement of central nociception and of peripheral myofascial factors in the chronic and in the episodic forms of tension‐type headache.

Reduced density of dopamine D2-like receptors on peripheral blood lymphocytes in Alzheimer's disease

Clinical and pathological evidence points to an involvement of dopamine in Alzheimers disease (AD). The present study was designed to assay dopamine D1-like and D2-like receptors on peripheral blood lymphocytes (PBL) in 20 patients with AD and in 25 healthy controls by radioligand binding assay techniques with [3H][R]-(+)-(-)chloro-2,3,4,5 tetrahydro-5-phenyl-1H-3-benzazepin-al-hemimaleate (SCH 23390) and [3H]7-hydroxy-N,N-di-n-propyl-2-aminotetraline (7OH-DPAT) as radioligands. The density of dopamine D1-like receptors and the affinity of [3H]SCH 23390 and [3H]7OH-DPAT binding to PBL were similar in both groups investigated. AD patients revealed a lower density of dopamine D2-like receptors on PBL than controls (P=0. 0016). The pharmacological profile of [3H]SCH 23390 and [3H]7OH-DPAT binding to PBL was consistent with the labeling of dopamine D5 and D3 receptor subtypes, respectively. The reduced density of dopamine D2-like receptors on PBL is consistent with the observation of changes in the expression of D2-like receptors in dopaminergic brain areas in AD. Our findings support the hypothesis of an involvement of dopamine in AD, even in those patients with no evidence of Parkinsonism, behavioral abnormalities or psychosis.