Coenzyme Q10‐responsive ataxia: 2‐year‐treatment follow‐up

We assessed the clinical outcome after coenzyme Q₁₀ (CoQ₁₀) therapy in 14 patients presenting ataxia classified into two groups according to CoQ₁₀ values in muscle (deficient or not). We performed an open‐label prospective study: patients were evaluated clinically (international cooperative ataxia rating scale [ICARS] scale, MRI, and videotape registration) at baseline and every 6 months during a period of 2 years after CoQ₁₀ treatment (30 mg/kg/day). Patients with CoQ₁₀ deficiency showed a statistically significant reduction of ICARS scores (Wilcoxon test: P = 0.018) after 2 years of CoQ₁₀ treatment when compared with baseline conditions. In patients without CoQ₁₀ deficiency, no statistically significant differences were observed in total ICARS scores after therapy, although 1 patient from this group showed a remarkable clinical amelioration. Biochemical diagnosis of CoQ₁₀ deficiency was a useful tool for the selection of patients who are good candidates for treatment as all of them responded to therapy. However, the remarkable clinical response in 1 case without CoQ₁₀ deficiency highlights the importance of treatment trials for identification of patients with CoQ₁₀‐responsive ataxia. © 2010 Movement Disorder Society     

Intrinsic functional and structural connectivity of emotion regulation networks in obsessive‐compulsive disorder

Despite emotion regulation being altered in patients with obsessive‐compulsive disorder (OCD), no studies have investigated its relation to multimodal amygdala connectivity. We compared corticolimbic functional and structural connectivity between OCD patients and healthy controls (HCs), and correlated this with the dispositional use of emotion regulation strategies and with OCD severity. OCD patients (n = 73) and HCs (n = 42) were assessed for suppression and reappraisal strategies using the Emotion Regulation Questionnaire (ERQ) and for OCD severity using the Yale‐Brown Obsessive‐Compulsive Scale. Resting‐state functional magnetic resonance imaging (rs‐fMRI) connectivity maps were generated using subject‐specific left amygdala (LA) and right amygdala (RA) masks. We identified between‐group differences in amygdala whole‐brain connectivity, and evaluated the moderating effect of ERQ strategies. Significant regions and amygdala seeds were used as targets in probabilistic tractography analysis. Patients scored higher in suppression and lower in reappraisal. We observed higher rs‐fMRI RA–right postcentral gyrus (PCG) connectivity in HC, and in patients this was correlated with symptom severity. Reappraisal scores were associated with higher negative LA–left insula connectivity in HC, and suppression scores were negatively associated with LA–precuneus and angular gyri connectivity in OCD. Structurally, patients showed higher mean diffusivity in tracts connecting the amygdala with the other targets. RA–PCG connectivity is diminished in patients, while disrupted emotion regulation is related to altered amygdala connectivity with the insula and posterior brain regions. Our results are the first showing, from a multimodal perspective, the association between amygdala connectivity and specific emotional processing domains, emphasizing the importance of amygdala connectivity in OCD pathophysiology.     

Denny-Brown sensory neuropathy disclosing a bilateral ovarian adenocarcinoma

The authors report the case of a 76 year-old woman examined because of occurrence of a paraneoplastic sensory neuropathy. Three months later, she developed a left inguinal adenopathy, metastasis of a bilateral ovarian adenocarcinoma. This case of particular interest in view of the way the neoplasm was discovered. The sensory neuropathy was previously reported to be associated with an ovarian cancer in only one case of the literature. Besides the tumor masse only limited to a left inguinal adenopathy, in this case emphasizes the ability of these rare metastasis. The ovarian cancer-associated antigen CA 125 is particularly useful for the diagnosis when high levels are found. In the absence of a pelvic tumor masse, the paraneoplastic sensory neuropathy, as well as the high levels of CA 125, have resulted in an exploratory laparotomy with extemporaneous examination of the ovaries, enabling to make the diagnosis of bilateral ovarian adenocarcinoma.     

The relationship between carotid atherosclerosis and platelet aggregation in elderly

The aim of this study is to assess the relationship between the carotid wall intima media thickness (IMT) and atheroma plaques due to atherosclerosis and platelet aggregation among elderly. The first stage of the study was performed by analyzing platelet aggregation in a total of 28 elderly patients divided into two groups. The first group consisted of 14 cases with carotid atheroma plaque (Patient group I) and the second group of patients were without carotid atheroma plaque (Control group I). At the second stage of the study, the cases were regrouped according to the carotid IMT. Patients with IMT above 1 mm (Patient group II, n=10) and under 1 mm (Control group II, n=14) were compared regarding platelet aggregation. Platelet aggregation was induced in the platelet-rich plasma using 5 micro M ADP, 0.2 mg/ml collagen and 1.2 mg/ml ristocetin. Between patients with and without atheroma, no difference was noted in terms of platelet aggregation. Between platelet aggregation results of patients with intimal thickness above and under 1 mm, no significant difference was also noted. Between elderly cases with or without atherosclerosis, there was no difference with respect to platelet aggregation. Platelet aggregation measurements cannot be used as a marker of atherosclerosis in elderly population.     

Counteraction of type 1 diabetic alterations by engineering skeletal muscle to produce insulin: insights from transgenic mice

Insulin replacement therapy in type 1 diabetes is imperfect because proper glycemic control is not always achieved. Most patients develop microvascular, macrovascular, and neurological complications, which increase with the degree of hyperglycemia. Engineered muscle cells continuously secreting basal levels of insulin might be used to improve the efficacy of insulin treatment. Here we examined the control of glucose homeostasis in healthy and diabetic transgenic mice constitutively expressing mature human insulin in skeletal muscle. Fed transgenic mice were normoglycemic and normoinsulinemic and, after an intraperitoneal glucose tolerance test, showed increased glucose disposal. When treated with streptozotocin (STZ), transgenic mice showed increased insulinemia and reduced hyperglycemia when fed and normoglycemia and normoinsulinemia when fasted. Injection of low doses of soluble insulin restored normoglycemia in fed STZ-treated transgenic mice, while STZ-treated controls remained highly hyperglycemic, indicating that diabetic transgenic mice were more sensitive to the hypoglycemic effects of insulin. Furthermore, STZ-treated transgenic mice presented normalization of both skeletal muscle and liver glucose metabolism. These results indicate that skeletal muscle may be a key target tissue for insulin production and suggest that muscle cells secreting basal levels of insulin, in conjunction with insulin therapy, may permit tight regulation of glycemia.