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During the last decades, symptomatic treatment of motor symptoms of Parkinson's disease (PD) improved continuously and is reflected by long-range independency of the patient during the disease course. However, advanced stages of PD still represent an important challenge to patients, caregivers and treating physicians. In patients with advanced PD, interventional therapy strategies are increasingly applied. These device-related treatment strategies using pump-based continuous dopaminergic stimulation (CDS) or deep brain stimulation (DBS) opened new treatment options especially if motor complications predominate. Well-designed clinical studies on these interventional therapeutic approaches provided class 1 evidence for the efficacy of DBS and CDS in advanced PD and opened new perspectives for their use in earlier disease stages also. Therefore, careful selection of patients amenable to the (semi)invasive therapy options becomes more and more important and requires an interdisciplinary setting that accounts for (i) optimal patient information and awareness, (ii) selection of best individual treatment modality, (iii) training of relatives and caregivers, (iv) management of complications, and (v) follow-up care. Here, we address these topics by summarizing current state-of-the-art in patient selection, providing specificities of treatment options and troubleshooting, and defining steps towards an optimized patient-centered care. Interventional therapies pioneer in the area of individualized treatment approaches for PD, and may be complemented in the future by biomarker-based improved stratification and by closed-loop systems for adaptive therapeutic strategies. In the present review, we summarize the proceedings of an Expert Workshop on Parkinson's disease held on November 22, 2014 in Frankfurt, Germany. [ABSTRACT FROM AUTHOR]

SCA28 is caused by mutations in the AFG3L2 gene. This gene encodes a subunit of the mitochondrial metalloprotease AFG3L2 (AFG3-like protein 2). Clinical features of SCA28 include slow to moderate progressive ataxia, dysarthria, and additional symptoms such as nystagmus, slow saccades, and increased deep tendon reflexes. Here, we report on a novel AFG3L2 mutation in a patient with slowly progressive ataxia and a positive family history. The nucleotide change results in the substitution of an evolutionarily highly conserved tyrosine by histidine (p.Y689H) in the M41 peptidase domain of AFG3L2. [ABSTRACT FROM AUTHOR]

Motor complications impair quality of life and cause severe disability in patients with advanced Parkinson's disease (PD). Since they are often refractory to medical therapy, interventional therapies have been developed, which can provide a considerable reduction of daily off-time and dopaminergic dyskinesias. Continuous dopaminergic drug delivery (CDD) is based on the steady stimulation of striatal dopamine receptors by subcutaneous apomorphine or duodenal l-DOPA infusions via portable minipumps. Advances in the understanding of basal ganglia functioning and in neurosurgical, electrophysiological and neuroimaging techniques have led to a renaissance of neurosurgery for advanced PD. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is the most invasive procedure promising great benefit and the highest level of independency for suitable patients, but is definitely associated with surgical risks and DBS-related side effects. Each of these more or less invasive therapy options has its own profile, and a thorough consideration of its advantages and drawbacks for the individual situation is mandatory. In this paper, we summarize relevant facts for this decision and provide some guidelines for a responsible counseling of eligible patients. [ABSTRACT FROM AUTHOR]

To further evaluate (1) transcranial sonography (TCS) for (pre)clinical diagnosis of Parkinson's disease (PD) and (2) to examine asymptomatic carriers of Parkin mutations we investigated substantia nigra (SN) hyperechogenicity in PD patients and unaffected subjects with and without Parkin mutations. The area (aSN) of the hyperechogenic SN were calculated bilaterally and study subjects were assigned to high versus low value groups. Eleven of the (affected and unaffected) mutation carriers had previously undergone 18-fluoro-dopa-(FDOPA)-PET scans. Fifty-eight individuals were investigated, including 24 with clinically definite and 34 without symptoms or signs of PD. Of the patients, three had one mutated and six had two mutated Parkin alleles. Of the unaffected subjects, 13 carried a single Parkin mutated allele. After dichotomization, 21 subjects had high and 37 subjects low values of mean aSN. Regarding the clinical status, 13 (62%) of the individuals with a high mean aSN had PD,while 26 (70%) of the study subjects with low values did not show signs of PD (p = 0.0393). Similarly, probands with high mean aSN values more frequently carried Parkin mutations (58%) than probands with low values (27%, p = 0.0234). A negative correlation between FDOPA uptake in the posterior putamen and maximum aSN was found in the group of mutation carriers (r = –0.809, p = 0.0234). In conclusion, hyperechogenicity of the SN is found in both idiopathic and Parkin-associated PD. Further strengthening the notion of a potential relationship between SN hyperechogenicity and Parkin mutational status, a larger aSN was associated with an increasing number of mutated alleles in our study. [ABSTRACT FROM AUTHOR]