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Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are in the spectrum of tauopathies and recognized to have a strong genetic background. It has been widely reported that MAPT tau haplotype H1 is a genetic risk factor in both conditions, but no other genetic determinants have so far been proposed. Recently, vascular endothelial growth factor (VEGF) haplotypes were reported to confer risk to frontotemporal dementia (FTD). The aim of this study was to evaluate the role of VEGF genetic determinants in PSP and CBS susceptibility. We evaluated a cohort of 687 unrelated Italian subjects, including 117 PSP, 108 CBS, 199 FTD, and 263 healthy controls. Genotype and allele frequencies of three well-known polymorphisms located within the VEGF promoter (-2578C/A, -1190G/A, and -1154G/A) were carried out. Genetic analysis revealed the presence of significant changes in terms of genotype and allele distributions in patients compared to healthy controls. A-G-G haplotype (-2578C/A, 1190G/A, -1154G/A) was overrepresented in both PSP (OR=6.64, 95% CI=2.3-19.6, P=0.0003, CGG=reference) and CBS (OR=5.20, 95% CI=1.70-15.9, P=0.003, CGG=reference) compared to healthy subjects. No differences between PSP and CBS and FTD were found, and the A-G-G haplotype was also overrepresented in FTD. Overall, these data suggest that VEGF gene variability represents a susceptibility factor for PSP and CBS. These data argue that additional genes may confer disease risk to PSP and CBS, and to FTD as well, beyond the MAPT tau haplotype. Further studies are warranted.

We analysed the parkin gene in a large consecutive series (146) of unrelated early onset Parkinson's disease (onset ?40 years of age) patients. Twelve cases (8.2%) had homozygous or compound heterozygous point mutations and/or exon rearrangements, while a single mutation was found in four subjects (2.7%). We identified eight exon rearrangements and nine point mutations, two of which were novel: c.735delT (p.C212/X224) and c.815C>G (p.C238W). Genotype-phenotype correlation revealed that parkin carriers had features similar to those of non-carrier early onset Parkinson disease patients.

We analysed the Leucine-Rich Repeat Kinase 2 (LRRK2) gene for the G2019S mutation in 1245 consecutive, unrelated patients with primary degenerative parkinsonism, and collected information on medical history, motor, cognitive and neuropsychiatric functions to characterize the clinical phenotype associated to the G2019S mutation. The mutation was detected in heterozygous state in 19 probands (1.7%), and in five additional affected relatives. Clinical features in carriers were those of typical, idiopathic Parkinson's disease. However, behavioural abnormalities were frequent (87%), suggesting a more widespread limbic involvement in G2019S carriers.

We assessed the effect of 3-month treatment of sertraline (50 mg) or low-dose amitriptyline (25 mg) on depression and quality of life in 31 patients with Parkinson's disease in a prospective single-blind randomized study. Both drugs significantly reduced the Hamilton Depression Rating Scale (HDRS-17) score. Completion rate was 75% for sertraline (12 of 16) and 73% for amitriptyline (11 of 15). Responder rate (HDRS-17 score reduction >/= 50%) was 83.3% for sertraline and 72.7% for amitriptyline. Sertraline but not amitriptyline treatment determined a significant benefit on quality of life (PDQ-39 scale). We found no change in Unified Parkinson's Disease Rating Scale scores. However, the improvement in specific PDQ-39 subscores (mobility, activities of daily living, and stigma) suggests that depression affects patient self-perception of motor function and further emphasizes the need for its treatment., ((c) 2006 Movement Disorder Society)

Background and Purpose: Quantitative evaluation of midbrain atrophy may be useful in differentiating progressive supranulear palsy (PSP) from Parkinson disease (PD); however, this finding is not specific of PSP, and quantitative measurements are not always practical. We determined whether an abnormal superior midbrain profile (flat or concave aspect) is a more practical diagnostic parameter for PSP., Methods: MR imaging studies of 25 patients with PSP and 27 with PD were reviewed by means of five parameters: midbrain superior profile on midsagittal T1-weighted images, midbrain atrophy, tegmental abnormal T2 hyperintensity, abnormal T2 putaminal hypointensity or hyperintensity on axial proton density-weighted images. We also measured the anteroposterior diameter of the midbrain on axial T2-weighted sections at the level of the superior colliculus., Results: The finding of an abnormal superior profile of the midbrain had 68% sensitivity and 88.8% specificity. Midbrain atrophy had 68% sensitivity and 77.7% specificity. Tegmental T2 hyperintensity had 100% specificity but poor sensitivity (28%). Only 14.8% of patients with PD and 24% of those with PSP had abnormal putaminal T2 hypointensity; none had proton-density hyperintensity. With PSP, the average midbrain diameter was smaller than that with PD, but an important overlap was observed. Reader discordance was lower for the midbrain superior profile sign (eight of 52 cases); this was similar for tegmental hyperintensity (nine of 52 cases) and higher for midbrain atrophy (16 of 52 cases)., Conclusion: An abnormal superior profile of the midbrain facilitates the distinction of PSP from PD and may support the clinical differential diagnosis of parkinsonism.

We studied the effects of acetyl-L-carnitine on pain in 16 HIV+ patients affected by painful distal symmetrical neuropathy. Patients were treated with 0.5-1 gr per day of acetyl-L-carnitine either i.m. or i.v. for 3 weeks. Pain intensity was measured before and after the treatment by the Huskisson's analogic scale. Ten patients (62.5%) reported an improvement of symptoms, five patients (31.25%) were unchanged, one patient worsened. The results of this open study show that acetyl-L-carnitine can have a role in the treatment of pain in distal symmetrical polyneuropathy related to HIV infection. However, further double-blind, placebo-controlled studies are needed to confirm these preliminary results.

Marked reduction in the contents of L-carnitine and acetyl-L-carnitine has been reported in peripheral nerves of rats with experimental diabetes. Since these substances have been claimed to improve a number of signs and symptoms of peripheral neuropathy in controlled clinical trials, this study was aimed at assessing whether nerves from diabetic subjects would also reveal similar decrease in the concentration of L-carnitine and acetyl-L-caritine. To this end, these substances were measured in nerves obtained from 11 patients with diabetic neuropathy, 13 patients with ischemic non-diabetic neuropathy, and 12 normal controls. Nerves from patients with either diabetic neuropathy and ischemic non-diabetic neuropathy showed levels of both carnitines lower than those from normal controls. However, differences among the three groups were not statistically significant, indicating that a reduction in these amino acids probably represents only a co-factor in the development of the variegated clinical picture of human diabetic neuropathy.