A randomized pilot study of stochastic vibration therapy in spinocerebellar ataxia.

Whole body vibration (WBV) is a biomechanical treatment used widely in professional sports and rehabilitation. We examined the effect of stochastic WBV on ataxia in spinocerebellar ataxia types 1, 2, 3, and 6 (SCA 1, 2, 3 and 6) in a single-center double-blind sham-controlled study. Stochastic WBV was applied on four sequent days, each treatment consisting of five stimulus trains of 60-s duration at a frequency of 6.5 Hz and 60-s resting time between stimuli (n = 17). Patients allocated to the sham group received the same treatment with 1 Hz (n = 15). All patients were rated at baseline and after the last treatment using clinical scores (SARA, SCAFI, and INAS). After treatment, we found significant improvements of gait, posture, and speed of speech in the verum group while limb kinetics and ataxia of speech did not respond. Stochastic WBV might act on proprioceptive mechanisms and could also stimulate non-cerebellar/compensatory mechanisms. But at present, the involved cellular mechanism and the presumed neuronal loops cannot be deciphered. Thus, future work is needed to understand the mechanisms of whole body vibration. Finally, the use of stochastic WBV could provide a supplementation to treat ataxia in SCA and can be combined with physiotherapeutical motor training.

Comparative study of the neurotrophic effects elicited by VEGF-B and GDNF in preclinical in vivo models of Parkinson's disease.

Vascular endothelial growth factor B (VEGF-B) has recently been shown to be a promising novel neuroprotective agent for several neurodegenerative conditions. In the current study we extended previous work on neuroprotective potential for Parkinson's disease (PD) by testing an expanded dose range of VEGF-B (1 and 10 µg) and directly comparing both neuroprotective and neurorestorative effects of VEGF-B in progressive unilateral 6-hydroxydopamine (6-OHDA) PD models to a single dose of glial cell line-derived neurotrophic factor (GDNF, 10 µg), that has been established by several groups as a standard in both preclinical PD models. In the amphetamine-induced rotational tests the treatment with 1 and 10 µg VEGF-B resulted in significantly improved motor function of 6-OHDA-lesioned rats compared to vehicle-treated 6-OHDA-lesioned rats in the neuroprotection paradigm. Both doses of VEGF-B caused an increase in tyrosine hydroxylase (TH)-positive cell and fiber count in the substantia nigra (SN) and striatum in the neuroprotective experiment. The effect size was comparable to the effects seen with GDNF. In the neurorestoration paradigm, VEGF-B injection had no significant effect in either the behavioral or the immunohistochemical analyses, whereas GDNF injection significantly improved the amphetamine-induced rotational behavior and reduced TH-positive neuronal cell loss in the SN. We also present a strong positive correlation (p=1.9e-50) of the expression of VEGF-B with nuclear-encoded mitochondrial genes involved in fatty acid metabolism in rat midbrain, pointing to the mitochondria as a site of action of VEGF-B. GDNF showed a positive correlation with nuclear-encoded mitochondrial genes that was not nearly as strong (p=0.018). VEGF-B counteracted rotenone-induced reduction of (a) fatty acid transport protein 1 and 4 levels and (b) both Akt protein and phosphorylation levels in SH-SY5Y cells. We further verified VEGF-B expression in the human SN pars compacta of healthy controls and PD patients, in neuronal cells that show co-expression with neuromelanin. These results have demonstrated that VEGF-B has potential as a neuroprotective agent for PD therapy and should be further investigated.

Inventory of Non-Ataxia Signs (INAS): validation of a new clinical assessment instrument.

Although ataxia is by definition the prominent symptom of ataxia disorders, there are various neurological signs that may accompany ataxia in affected patients. Reliable and quantitative assessment of these signs is important because they contribute to disability, but may also interfere with ataxia. Therefore we devised the Inventory of Non-Ataxia Signs (INAS), a list of neurological signs that allows determining the presence and severity of non-ataxia signs in a standardized way. INAS underwent a rigorous validation procedure that involved a trial of 140 patients with spinocerebellar ataxia (SCA) for testing of inter-rater reliability and another trial of 28 SCA patients to assess short-term intra-rater reliability. In addition, data of the ongoing EUROSCA natural history study were used to determine the reproducibility, responsiveness and validity of INAS. Inter-rater reliability and short-term test-retest reliability was high, both for the total count and for most of the items. However, measures of responsiveness, such as the smallest detectable change and the clinically important change were not satisfactory. In addition, INAS did not differentiate between subjects that were subjectively stable and those that worsened in the 2-year observation period. In summary, INAS and INAS count showed good reproducibility, but unsatisfactory responsiveness. The present analysis and published data from the EUROSCA natural history study suggest that INAS is a valid measure of extracerebellar involvement in progressive ataxia disorders. As such, it is useful as a supplement to the measures of ataxia, but not as a primary outcome measure in future interventional trials.

[Parkinson's disease. Perioperative management and anesthesia]. / Morbus Parkinson. Perioperatives Management und Anästhesie.

Approximately 10,000-15,000 Parkinson's disease (PD) patients per year undergo surgery in Germany. The demographic developments along with further surgical progress and procedural refinements will lead to increasing numbers of PD patients in the operating theatre (OR). There are several perioperative risk factors for PD patients, they more often require prolonged intensive care treatment and warrant particular anesthesiological attention with regard to the choice of drugs and equipment. Careful evaluation of concomitant diseases, maintenance of oral Parkinson therapeutic drugs up to the time of surgery and continuous perioperative dopaminergic therapy are key factors for reducing postoperative morbidity in PD patients undergoing surgery.

Tremor in Parkinson's disease is not associated with the DRD3 Ser9Gly polymorphism.

A common subset of genetic risk factors for Parkinson's disease (PD) and essential tremor (ET) has been postulated. Recently, an association between the dopamine D(3) receptor (DRD3) Ser9Gly polymorphism and ET has been reported. We studied whether PD tremor is influenced by Ser9Gly in a genetic association study based on the gene bank of the German Competence Network on Parkinson's disease. The study included analyses of motor predominance (mixed, hypokinetic, and tremor), and tremor type (resting, postural, and action). We did not identify any effect of DRD3 Ser9Gly on tremor in PD, even when regarding various symptom combinations to avoid missing a weak effect on the phenotype. Additional studies incorporating symptoms at disease onset, and grading of tremor response to dopaminergic therapy, are warranted.

Improvement of paraplegia caused by spinal dural arteriovenous fistula by surgical obliteration more than 6 years after symptom onset.

Spinal dural arteriovenous fistulae (SDAVF) are acquired spinal vascular malformations, in which a small connection between a radicular artery and radicular vein causes venous hypertension, congestive myelopathy and infarction of the spinal cord. Here the case of a 47-year-old man is presented who had pain in his back irradiating to his right leg, numbness of his right leg as well as weakness of both legs. Urination was disturbed with detection of residual urine. Six weeks later he developed a progressive paraparesis of the legs. A T2 weighted MRI of the lower back showed intramedullary hyperintensity. A myelitis was assumed and treatment with acyclovir and dexamethasone was started. Nevertheless, he developed total paralysis of his legs. Six years later, re-evaluation of the initial MRI and a new MRI showed abnormal blood vessels on the dorsal side of the spinal cord, which had been overlooked at the first MRI examination. Spinal angiography demonstrated an arteriovenous fistula. Fistula obliteration was performed. Six months later he was able to stand with canes for 2 min and showed improvement in sensibility. The remarkable aspect of this case of SDAVF is the relevant improvement of complete paraplegia by surgical obliteration 78 months after onset of symptoms. The delay of more than 6 years between onset of first symptoms and final diagnosis underlines the difficulties in making a correct diagnosis of SDAVF. However, even after delayed diagnosis, surgical obliteration should be done, as improvement of neurological function can still be achieved.