Investigation of unmedicated early onset restless legs syndrome by voxel-based morphometry, T2 relaxometry, and functional MR imaging during the night-time hours.

BACKGROUND AND PURPOSE: The pathophysiology of eRLS has not yet been elucidated. The purpose of the study was to assess, in patients with eRLS, the volume, iron content, and activation of the brain during night-time episodes of SLD and PLMs. MATERIALS AND METHODS: Eleven right-handed unmedicated patients with eRLS (mean age, 55.3 ± 8.4 years; disease duration, 17.5 ± 14.05 years) and 11 matched control subjects were studied with a T1-weighted high-resolution 3D spoiled gradient-echo sequence used for VBM and a multisection spin-echo T2-weighted sequence used for T2 relaxometry. Additionally, a single-shot multisection gradient echo-planar sequence was used for fMRI. Brain activation was recorded during spontaneous SLD and PLMs. SPM software was used for analysis of the functional data. RESULTS: The patients showed no regional brain volume change, but T2 relaxometry revealed decreased T2 relaxation time in the right globus pallidus internal and the STN, indicating increased iron content. The patients were observed to activate the following areas: in the left hemisphere, the primary motor and somatosensory cortex, the thalamus, the pars opercularis, and the ventral anterior cingulum; and in the right hemisphere, the striatum, the inferior and superior parietal lobules, and the dorsolateral prefrontal cortex. Bilateral activation was observed in the cerebellum, the midbrain, and the pons. CONCLUSIONS: eRLS is associated with increased iron content of the globus pallidus internal and STN, suggesting dysfunction of the basal ganglia. Activation of the striatofrontolimbic area may represent the neurofunctional substrate mediating the repetitive compulsive movements seen in RLS.

Treatment of motor symptoms in advanced Parkinson's disease: a practical approach.

Patients with advanced Parkinson's disease (PD) are known to develop motor complications after a few years of levodopa (L-dopa) therapy. Motor fluctuations develop with increasing severity of the disease, owing to loss of dopaminergic neurons and loss of the buffering capacity of the neurons to fluctuating dopamine levels. Dyskinesias develop as a result of pulsatile stimulation of the receptors and alterations in neuronal firing patterns. L-dopa remains the gold standard medication for the treatment of patients with advanced PD. However, once motor complications on L-dopa therapy emerge, clinicians may add on other classes of antiparkinsonian drugs such as dopamine agonists, catechol-O-methyl transferase inhibitors (COMTIs) or monoamine oxidase type B inhibitors (MAOBIs). The individualisation of the treatment seems to be the key for the best approach of advanced PD patients. The present review provides the most important current clinical data in the pharmacological treatment of motor symptoms in advanced PD and provides the clinician a simple algorithm in order to determine the best suitable treatment to advanced parkinsonian patients.

How should we treat a patient with early Parkinson's disease?

Parkinson's disease (PD) is characterised by the progressive degeneration of dopaminergic nigro-striatal neurons and severe striatal dopaminergic deficiency, leading to bradykinesia. Levodopa was the first drug used for PD treatment and is still considered the most useful weapon for the control of PD symptoms. However, levodopa treatment induces motor complications, which is considered as a major problem as the disease progresses. Dopamine agonists, catechol-O-methyltransferase inhibitors and monoamine oxidase B inhibitors are some more recently developed drug categories which are expected to have a more favourable effect on motor complications. The choice of the best initial treatment in PD remains a controversial matter. Early therapeutic decisions in PD should balance the need for efficient short-term symptom control against long-term complication profile. The individualisation of the treatment seems to be the key for the best approach of early PD patients.

Can atypical antipsychotics improve tardive dyskinesia associated with other atypical antipsychotics? Case report and brief review of the literature.

Tardive dyskinesia (TD) is a devastating adverse effect of long-term antipsychotic drug treatment. Atypical antipsychotics produce less TD, and it has been shown that they may have a therapeutic effect on pre-existing TD. Here, we report a case of olanzapine-induced TD which did not improve after switching to risperidone but improved after the addition of quetiapine to risperidone regimen. We also provide a brief review of the reported cases on TD induced by atypical antipsychotics which improved after switching to another atypical agent. It is unclear whether some atypical antipsychotics are more effective than others in the treatment of TD. Differences in this property and the underlying mechanism require further study.

Significance of aphasia after first-ever acute stroke: impact on early and late outcomes.

BACKGROUND: We assessed the incidence and determinants of aphasia attributable to first-ever acute stroke. We also investigated early and long-term mortality and 1-year dependence in post-stroke patients. METHODS: A 10-year prospective hospital-based study was conducted in the prefecture of Athens, Greece. RESULTS: In total, 2,297 patients were included in the study, of whom 806 (35.1%) had aphasia. The presence of aphasia was independently associated with increasing age (OR: 1.19 per 10-year increase, 95% CI: 1.12-1.21) and atrial fibrillation (OR: 1.35, 95% CI: 1.08-1.67), and inversely associated with Scandinavian Stroke Scale (SSS) score (OR: 0.55 per 10-point increase, 95% CI: 0.52-0.59) and hypertension (OR: 0.77, 95% CI: 0.63-0.96). One-year dependence score (calculated with the modified Rankin score) was higher in aphasic patients compared to non-aphasics (p < 0.001). Moreover, severity of aphasia (estimated with a subscale of SSS) was found as an independent predictor of 1-year dependence. Most of the deaths in the aphasic patients were attributed to infections and neurological damage. Using the Kaplan-Meier limit method, the unadjusted probability of 10-year mortality was demonstrated to increase with the severity of aphasia (log-rank test: 233.9, p < 0.001) and, even after adjustment for several other factors, severity of aphasia remained an independent predictor of 10-year mortality. CONCLUSIONS: Increasing age, atrial fibrillation and severity of stroke were associated with the risk of aphasia after stroke. Severity of aphasia is a strong predictor of long-term mortality and dependence of post-stroke patients.

T2 relaxometry and fMRI of the brain in late-onset restless legs syndrome.

OBJECTIVE: To assess in patients with late-onset idiopathic restless legs syndrome (RLS) the brain iron content with magnetic resonance relaxometry, and brain activation during dorsiflexion and plantar flexion of both feet, using fMRI. METHODS: The study was approved by the institutional review board, and informed consent was obtained. Twenty-five RLS patients (14 women, 11 men; age range 55-82 years; mean 66.5 +/- 8.9 years; disease duration 6.5 +/- 4.5 years) and 12 sex- and age-matched controls were studied. A T1-weighted high-resolution three-dimensional spoiled gradient echo sequence was used for structural imaging, a multislice spin echo Tau2-weighted sequence was used for T2 relaxometry, and a single-shot multislice gradient echo planar sequence was used for fMRI. The motor paradigm consisted of alternating periods of rest and movement, each 40 seconds in duration. Region of interest analysis was used on the T2 relaxometry maps. Statistical parametric mapping software was used for analysis of the functional data. RESULTS: T2 relaxation time was significantly higher in patients than in controls in the substantia nigra pars compacta. Within-group analysis showed that both patients and controls activated the primary motor cortex, the primary somatosensory cortex, the somatosensory association cortex, and the middle cerebellar peduncles. Patients also activated the thalamus, putamen, middle frontal gyrus, and cingulate gyrus. Between-group analysis showed that patients had higher activation of the dorsolateral prefrontal cortex. CONCLUSION: Late-onset restless legs syndrome is associated with low iron content of the basal ganglia and increased activity of the dorsolateral prefrontal cortex.

Effects of sibutramine and orlistat on mood in obese and overweight subjects: a randomised study.

BACKGROUND AND AIM: Intentional weight loss results in improvement in mood. Very few data exist regarding the effects of sibutramine on the mood of obese and overweight patients in general clinical samples. Moreover, no study has evaluated the effects of orlistat treatment on mood. The purpose of our study was to assess the effects of sibutramine and orlistat on mood in obese and overweight subjects. METHODS AND RESULTS: Sixty obese and overweight women were divided into three groups. The first group (n=20) received a low-calorie diet and sibutramine 10mg; the second group (n=20) received a low-calorie diet and orlistat 120 mg three times a day, and the third group received only the low-calorie diet. CONCLUSION: A psychiatric assessment was performed with the Hamilton Depression Rating Scale (HAMD) before and after 3 months of treatment. In all the groups a statistically significant decrease in HAMD scores was observed. However, the decrease in the sibutramine group was greater compared to that observed in the two other groups (P<0.01). These results suggest that sibutramine treatment may improve mood more than diet alone or orlistat therapy in a general clinical sample of obese patients.

Preventing type 2 diabetes in high risk patients: an overview of lifestyle and pharmacological measures.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a common disease that is associated with an increased risk of vascular complications. The incidence of T2DM is also increasing. It follows that T2DM prevention is important. METHODS: Relevant articles (review articles, randomised studies and large cohort and case-control studies) were identified through a Medline search (up to March 2005). RESULTS: The first trials on T2DM prevention were based on lifestyle intervention. The results of these studies were impressive since they demonstrated that even a small reduction in weight could significantly reduce the incidence of T2DM. However, the main disadvantage of lifestyle measures is that they are difficult to achieve and sustain. Therefore, pharmacological interventions have also been evaluated. The results of trials using metformin, orlistat, nateglinide, acarbose, thiazolidinediones, hormone replacement therapy, statins or fibrates are either encouraging or require more extensive evaluation. In addition, studies using antihypertensive drugs (mainly angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists) showed that these drugs could also reduce the progression to T2DM in high risk individuals. CONCLUSIONS: T2DM has major quality of life and cost implications. Therefore, more research is needed to establish safe and cost effective ways to prevent this modern epidemic.

Pathogenesis, detection and treatment of Achilles tendon xanthomas.

Tendon xanthomatosis often accompanies familial hypercholesterolaemia, but it can also occur in other pathologic states. Achilles tendons are the most common sites of tendon xanthomas. Low-density lipoprotein (LDL) derived from the circulation accumulates into tendons. The next steps leading to the formation of Achilles tendon xanthomas (ATX) are the transformation of LDL into oxidized LDL (oxLDL) and the active uptake of oxLDL by macrophages within the tendons. Although physical examination may reveal Achilles tendon xanthomas (ATX), there are several imaging methods for their detection. It is worth mentioning that ultrasonography is the method of choice in everyday clinical practice. Although several treatments for Achilles tendon xanthomas (ATX) have been proposed (LDL apheresis, statins, etc.), they target mostly in the treatment of the basic metabolic disorder of lipid metabolism, which is the main cause of these lesions. In this review we describe the formation, detection, differential diagnosis and treatment of ATX as well as the relationship between tendon xanthomas and atheroma.