Giovanni Iliceto

Freezing Gait in Parkinson's Disease

Freezing is a well-known problem in Parkinsons disease (PD) and is characterized by an abrupt difficulty in starting or continuing rhythmic and repetitive movements. We utilized a questionnaire in order to assess the occurrence of the freezing gait phenomenon (FG) in a population of 100 consecutive PD patients. Our PD population included 70 males and 30 females, with a mean age of 61.1 +/- 9.1 years. Mean duration of PD was 6.5 +/- 4.0 years. 92/100 patients were under L-Dopa treatment. The FG phenomenon occurred in 60% of patients. It appeared on average 4.8 years after the beginning of PD; in 16% of the cases it was evident before starting L-Dopa treatment. FG was more frequent among female patients. There was no significant correlation between the occurrence of FG and the age of the patients; on the other hand, a significant correlation was found with the duration of the disease (p < 0.001). FG occurred more frequently in the subgroup of patients with the akinetic form (odds ratio: 3.05); whilst an opposite tendency was evident in the subgroup with the tremor predominant form (odds ratio: 0.29).

Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson's disease patients

Homocysteine (Hcy) is a risk factor for vascular diseases, cognitive impairment, and dementia. Elevated plasma concentrations of Hcy have been found recently in Parkinsons disease (PD) patients treated with levodopa, suggesting that levodopa is a cause of hyperhomocysteinemia (HHcy). The mechanism underlying HHcy in PD is the O‐methylation of levodopa catalyzed by catechol‐O‐methyltransferase (COMT) that produces S‐adenosylhomocysteine, which is hydrolyzed rapidly to Hcy. COMT inhibitors (COMT‐I) are used currently in the treatment of PD; however, no study has assessed the effects of COMT‐I administration on Hcy concentrations in PD patients. We compared plasma levels of Hcy, B12, and folate in 26 PD patients treated with levodopa, 20 PD patients treated with levodopa + COMT‐I, and 32 controls. No significant differences were found in vitamin B12 levels, whereas folate concentrations were significantly lower in the levodopa‐treated group. Plasma Hcy was increased significantly in the two groups of PD patients and was significantly lower in the group treated with levodopa + COMT‐I. Statistical analysis showed that the difference in mean Hcy levels observed among PD patients was related to the addition of COMT‐I, rather than to folate concentrations. We conclude that levodopa treatment increases plasma Hcy and the addition of COMT‐I effectively reduces HHcy.

Proton magnetic resonance spectroscopy in Parkinson's disease and progressive supranuclear palsy.

OBJECTIVES: Proton magnetic resonance spectroscopy (1H-MRS) localised to the lentiform nucleus, was carried out in eight patients with idiopathic Parkinsons disease and five patients with progressive supranuclear palsy. The aim of the study was to assess the concentration of N-acetyl-aspartate (NAA), creatine and phosphocreatine (Cr), and choline containing compounds (Cho) in the putamen and globus pallidus of these patients. METHODS: Peak ratios obtained from patients were compared with those from nine healthy age matched controls. RESULTS: NAA/Cho and NAA/Cr ratios were reduced significantly in patients with progressive supranuclear palsy. CONCLUSION: These results suggest an NAA deficit, due to neuronal loss, in the lentiform nucleus of these patients. 1H-MRS is a non-invasive technique that can provide useful information concerning striatal neuronal loss in the basal ganglia of patients with parkinsonian syndromes.

Hyperhomocysteinemia in L-dopa treated Parkinson's disease patients: effect of cobalamin and folate administration

Homocysteine (Hcy) is a risk factor for vascular diseases, cognitive impairment and dementia. l‐dopa treatment may represent an acquired cause of hyperhomocysteinemia (HHcy), as evidenced by studies in rats as well as in Parkinsons disease (PD) patients. Folate and cobalamin status also seems to influence the effects of l‐dopa on plasma Hcy levels; therefore B‐vitamins supplementation has been proposed to reduce the HHcy in l‐dopa treated PD patients. Plasma Hcy, folate, and cobalamin levels were evaluated in 20 PD patients treated with l‐dopa in the baseline condition and following a 5‐week period of treatment with cobalamin and folate; results were compared with 35 controls. Analysis of data revealed that Hcy levels were higher in l‐dopa treated PD patients when compared with age‐ and sex‐matched controls and that supplementation of the diet with cobalamin and folate is effective in reducing Hcy concentrations; these findings may have important implications in the treatment of PD patients who are potentially at risk for vascular diseases and cognitive impairment or dementia.

ALS-plus: 5 cases of concomitant amyotrophic lateral sclerosis and parkinsonism

Abstract. According to El Escorial criteria, amyotrophic lateral sclerosis (ALS), combined with other neurologic disorders, such as dementia and parkinsonism, is defined as ALSplus. These overlaping syndromes are extremely rare. Here we report 5 cases (3 men, 2 women) of ALS-plus; mean age at the onset of symptoms was 67 years (range, 65–72). In 3 patients, motoneuronal signs preceded the onset of parkinsonian syndrome. In 4 cases, the clinical picture was characterized by the prevalence of motoneuronal signs. Parkinsonism was poorly responsive to L-dopa treatment in all patients. The clinical course did not differ from that expected in patients with only ALS. Our clinical observations and neuropathological reports of nigral neuronal loss in ALS patients suggest a common pathogenic mechanism underlying these disorders.

A case of concomitant amyotrophic lateral sclerosis and HIV infection.

In a recent study (Masterman et al., 2000), we catalogued clinicodemographic data for 816 patients with definite multiple sclerosis (MS) and investigated the impact of the MS-associated HLA class II specificity DR15 on aspects of the disease phenotype; we demonstrated, among other things, that carriage of DR15 is associated with lower age at onset in MS. The onset-hastening effect of DR15 was present in patients with both bout-onset [BO, i.e. relapsing-remitting (RR), progressive-relapsing or secondary progressive (SP)] MS (n 1⁄4 726, 29.9 years for carriers vs. 31.8 years for non-carriers, P 1⁄4 0.0041, Student’s t-test) and primary progressive (PP) MS (n 1⁄4 85, 37.0 years for carriers vs. 44.1 years for non-carriers, P 1⁄4 0.0023), a finding not presented in our original report (for five patients, information concerning either course or age at onset was unavailable). Thus, in MS, DR15-positive and DR15-negative genotypes exhibit what are called, in the context of quantitative-trait locus mapping, parallel norms of reaction (Fig. 1), i.e. their influence on the phenotypic character under investigation, age at onset, is preserved despite a change of ‘environment’ (Mackay, 2001). Here, it is the disease courses, BO MS and PP MS, that constitute the different environments. Despite indisputable clinical and neuroradiological distinctness, it remains unclear what, in terms of etiopathogenesis, underlies differences between BO and PP MS. However, the two broad classes of histopathological patterns in MS identified recently by Lucchinetti et al. (2000) – T-cell mediated, ‘autoimmune’ demyelination (patterns I and II), and primary oligodendrocyte dystrophy, ‘reminiscent of virusor toxin-induced demyelination’ (patterns III and IV) – corresponded, to some degree, to differences in clinical course. At the same time, experimental models of virus-induced demyelination often display a biphasic course (Stohlman and Hinton, 2001) – a facultative inflammatory phase, during which an immune response to a persistent CNS infection results in recurrent demyelination, is followed by a chronic phase, marked by loss of oligodendrocytes because of virusinduced apoptosis – suggesting that immune-mediated damage and oligodendrogliopathy can occur together, as serial stages of the same disorder. Paty and Ebers (1998) have studied the striking similarity between the age-atonset curve of PP MS patients, on the one hand, and the age-at-conversion (i.e. from RR to SP MS) curve of BO MS patients on the other. Moreover, Runmarker and Andersen (1993) demonstrated in a large cohort of Swedish patients that progression rates for PP and SP MS, from the onset of progression to a score of 6 on Kurtzke’s Disability Status Scale, were very similar. Based in part on our own observations concerning the unchanging impact of DR15 on the timing of the first appearance of MS symptoms, we speculate that BO MS and PP MS may turn out to have the same aetiology (or range of aetiologies). In addition, pathogenetically, it may turn out that, in MS, an ineluctable progressive phase of primary oligodendrogliopathy is, in about 8 out of 10 cases, preceded by a phase of partially reversible, immune-mediated demyelination, characterized clinically by relapses and remissions.

Elevated plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with dyskinesias

Abstract Background: Elevated plasma homocysteine (Hcy) concentrations are associated with increased risk of systemic vascular diseases, Alzheimers disease and vascular dementia. Several cross-sectional reports and two prospective clinical studies have recently reported elevated plasma Hcy levels in L-dopa-treated Parkinsons disease (PD) patients and Hcy has been proposed as a possible mediator for the development of long-term L-dopa motor complications (such as wearing off and on-off phenomena, and dyskinesias). The aim of the study was to elucidate a possible role of L-dopa-related hyperhomocysteinemia in the development of dyskinesias. Methods: In this cross-sectional study we compared Hcy, B12 and folate levels in 53 PD patients treated with L-dopa (29 with dyskinesias, 24 without dyskinesias). Results: Mean plasma Hcy levels were higher in the group of PD patients with dyskinesias (19 vs. 15.4 T: 2.12; p=0.04). After taking into account potential confounding factors, analysis of the data revealed that the occurrence of dyskinesias progressively increased with plasma Hcy levels (relative risk 1.2, 95% CI 1.015–1.4; p=0.03). Conclusions: Our results raise the possibility that Hcy plays a role in the development of dyskinesias, through its toxic effects on both dopaminergic neurons and non-substantia nigra, non-dopaminergic neurons. Clin Chem Lab Med 2006;44:863–6.

Action tremor in Parkinson's disease: frequency and relationship to motor and non‐motor signs

Action tremor may occur in patients with Parkinsons disease and cause misdiagnosis with other movement disorders such as essential tremor and dystonia. Data on the frequency of action tremor in Parkinsons disease and on the relationships with other motor and non‐motor signs are limited.

Post-vaccinic opsoclonus–myoclonus syndrome: a case report

The opsoclonus-myoclonus syndrome is a pathological condition characterized mainly by involuntary myoclonic movements involving ocular, trunk and limb muscles associated with ataxia and other neurological signs.We describe the case of a 30-year-old woman who developed this syndrome 15days after anti-Rubella vaccination. This case suggests a possible autoimmune post-vaccinic etiopathogenesis of opsoclonus-myoclonus syndrome, rarely described in the literature.

Motoneuron disease after electric injury: a case report

Several cases of motor neuron disease (MND) after electric injury have been reported in the last number of years, but the relationship between electric injury and MND remains controversial. Herein we report the case of a 60-year-old man who developed a MND following an electrical trauma. In the case presented here, the onset of disease at the site of lightning strike and the short interval of time between the electrical injury and the clinical onset of MND raise the possibility of considering electrical shock as a trigger factor for MND.