Lower limb involvement in adult‐onset primary dystonia: frequency and clinical features

Background and purpose: Despite the growing number of reports describing adult‐onset primary lower limb dystonia (LLD) this entity has never been systematically evaluated in the general population of patients with primary adult‐onset dystonia. Methods: From outpatients with adult‐onset primary dystonia attending nine Italian University centres for movement disorders we consecutively recruited 579 patients to undergo a standardized clinical evaluation. Results: Of the 579 patients assessed, 11 (1.9%) (8 women, 3 men) had LLD, either alone (n = 4, 0.7%) or as part of a segmental/multifocal dystonia (n = 7, 1.2%). The age at onset of LLD (47.9 ± 17 years) was significantly lower than the age at onset of cranial dystonias (57.9 ± 10.7 years for blepharospasm, and 58.9 ± 11.8 years for oromandibular dystonia) but similar to that of all the other adult‐onset primary dystonias. The lower limb was either the site of dystonia onset (36.4%) or the site of dystonia spread (63.6%). In patients in whom LLD was a site of spread, dystonia seemed to spread following a somatotopic distribution. Only one patient reported a recent trauma involving the lower limb whereas 36.4% of the patients reported pain at the site of LLD. Only 64% of our patients needed treatment for LLD, and similarly to previously reported cases, the most frequently tried treatments was botulinum toxin and trihexyphenidyl. Conclusion: The lower limb is an uncommon but possible topographical site of dystonia in adulthood that should be kept in consideration during clinical evaluation.     

In vitro modulation of adhesion molecules, adhesion phenomena, and fluid phase endocytosis on human umbilical vein endothelial cells and brain-derived microvascular endothelium by IFN-beta 1a.

Administration of interferon-beta (IFN-beta) in multiple sclerosis (MS) patients provides clinical benefits, although its mechanism(s) of action are not completely understood. We addressed the issue of whether concentrations of IFN-beta1a close to those reached in the serum of treated MS patients could modulate either adhesion molecules or adhesion of peripheral blood mononuclear cells (PBMC) as well as fluid phase endocytosis (FPE) in human umbilical vein endothelial cells (HUVEC) and in brain-derived microvascular endothelial cells (HBMEC). Adhesion was assessed by flow cytometry, and FPE was evaluated by peroxidase uptake. In our study, 200 U/ml IFN-beta1a induced a reduction in adhesion of PBMC to HUVEC. The information reported herein may contribute to further elucidating some of the mechanisms of action of IFN-beta on vascular endothelium.     

Hyaline droplet accumulation in kidney of rats treated with hexachloro‐1:3‐butadiene: influence of age,dose and time‐course

The present research investigates the occurrence of hyaline droplet (HD) accumulation related to age, dose and time after treatment in male Wistar rats given a single i.p. injection of hexachloro‐1:3‐butadiene (HCBD). In the study on age, rats from 1 to 12 months of age were treated with 100 mg kg^?1 body weight (b.w.) HCBD dose. Rats treated at 2 months of age showed a greater accumulation of HD than the other age groups; HD accumulation was not observed in 1‐month‐old rats. In the dose–response study, the treatment with 25, 50 and 100 mg kg^?1 b.w. at 2 months of age caused HD accumulation in the proximal convoluted tubule at all doses, with the 100 mg kg^?1 b.w. group slightly more affected. Finally, in the time‐course study, rats treated with a 100 mg kg^?1 b.w. dose at 2 months of age and sacrificed at 6, 12, 24, 48, 72 and 96 h post‐dosing showed a time‐related HD accumulation in terms of incidence and severity, after 6 h, with a peak at 24 and 48 h and decreasing at 72 and 96 h. The present results show that HD accumulation is an early finding, and is unrelated to dose level and particularly evident in rats of 2 month of age. These findings in male rats treated with HCBD emphasize the importance of considering the age of rats at the start of a study. The more sensitive model was used in the detection of nephrotoxic effects of chemicals. Copyright © 2011 John Wiley & Sons, Ltd.     

Mirror movements in patients with Parkinson's disease

Mirror movements (MM) refer to ipsilateral involuntary movements that appear during voluntary activity in contralateral homologous body regions. This study aimed to compare the frequency and distribution of MM in an unselected sample of 274 patients with Parkinson's disease (PD) and 100 healthy subjects, and to check a possible relationship between MM and parkinsonian features. MM of the hand were scored according to the Woods and Teuber scale. The frequency of MM was lower in PD patients than in healthy subjects (29% vs. 71%, P < 0.0001). The distribution of MM also differed in the two groups being often bilateral in healthy subjects, invariably unilateral in PD patients. When parkinsonian signs were unilateral, MM always manifested on the unaffected side; when parkinsonian signs were bilateral, MM manifested on the less affected side. PD patients manifesting MM scored significantly lower on Hohen and Yahr staging than patients without MM. Likewise, there was a significant inverse correlation between the intensity of MM as rated by the Woods and Teuber score and HY staging (r = ?0.16, P < 0.01). The low frequency of MM in PD probably relates to the complex interactions between the pathophysiological mechanisms leading to parkinsonian signs and the mechanisms responsible for movement lateralization. © 2007 Movement Disorder Society     

Bilateral striatal necrosis,dystonia and multiple mitochondrial DNA deletions: Case study and effect of deep brain stimulation

Bilateral striatal necrosis (BSN) is relatively rare and has been related to a wide array of causes, including nuclear and mitochondrial DNA mutations. We report the clinical vignette of a patient with a 37 years‐history of generalized dystonia secondary to BSN associated with multiple mitochondrial DNA deletions of undefined origin. Globus pallidus interna deep brain stimulation produced sustained benefit, with predominant improvements in disability. © 2007 Movement Disorder Society     

Evaluation of aging influence on renal toxicity caused by segment‐specific nephrotoxicants of the proximal tubule in rat†

Little is known concerning the sensitivity of aged rats to xenobiotics inducing kidney damage. To increase this knowledge, the age‐dependent response of the kidney to hexachloro‐1 : 3‐butadiene (HCBD) or potassium dichromate (chromate) was investigated. Rats were treated at different ages with a single dose of segment‐specific nephrotoxicants of the proximal tubule, chosen on the basis of their specificity for S₃ and for S₁–S₂ segments, respectively. The toxicological impact of these xenobiotics has been evaluated through biochemical and genomic markers, and histopathological investigation of kidney samples. HCBD treatment induced tubular necrosis of the S₃ segment of the proximal tubule associated with changes of toxicological markers unrelated to the age. In contrast, chromate treatment induced an increased kidney damage related to the rat age. In fact, histopathological investigation revealed that at 1 month of age tubular vacuolar degeneration was seen affecting S₁–S₂ segments of the proximal tubule, whereas at 3 months of age tubular necrosis occurred in the same segments associated with tubular dilation of the distal portions. Consistently, biochemical analysis confirmed a direct correlation among genomic and biochemical marker variability and animal age. Altogether, the results show that during aging there is an increased sensitivity of kidney to chromate but not to HCBD‐induced damage and evidence differential age‐related selectivity of rats for nephrotoxic compounds. Significance for human risk assessment is discussed. Copyright © 2009 John Wiley & Sons, Ltd.