Lewy body disease or diseases with Lewy bodies?

The current nosological concept of α-synucleinopathies characterized by the presence of Lewy bodies (LBs) includes Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB), for which the term "Lewy body disease" (LBD) has recently been proposed due to their considerable clinical and pathological overlap. However, even this term does not seem to describe the true nature of this group of diseases. The subsequent discoveries of α-synuclein (αSyn), SNCA gene, and the introduction of new immunohistochemical methods have started intensive research into the molecular-biological aspects of these diseases. In light of today's knowledge, the role of LBs in the pathogenesis and classification of these nosological entities remains somewhat uncertain. An increasingly more important role is attributed to other factors as the presence of various LBs precursors, post-translational αSyn modifications, various αSyn strains, the deposition of other pathological proteins (particularly ß-amyloid), and the discovery of selective vulnerability of specific cells due to anatomical configuration or synaptic dysfunction. Resulting genetic inputs can undoubtedly be considered as the main essence of these factors. Molecular-genetic data indicate that not only in PD but also in DLB, a unique genetic architecture can be ascertained, predisposing to the development of specific disease phenotypes. The presence of LBs thus remains only a kind of link between these disorders, and the term "diseases with Lewy bodies" therefore results somewhat more accurate.

Deep brain stimulation electrode position impact on parkinsonian non-motor symptoms.

BACKGROUND: In this study we evaluated the impact of location of deep brain stimulation electrode active contact in different parts of the subthalamic nucleus on improvement of non-motor symptoms in patients with Parkinson's disease. METHODS: The subthalamic nucleus was divided into two (dorsolateral/ventromedial) and three (dorsolateral, medial, ventromedial) parts. 37 deep brain stimulation electrodes were divided according to their active contact location. Correlation between change in non-motor symptoms before and one and four months after deep brain stimulation electrode implantation and the location of active contact was made. RESULTS: In dividing the subthalamic nucleus into three parts, no electrode active contact was placed ventromedially, 28 active contacts were located in the medial part and 9 contacts were placed dorsolaterally. After one and four months, no significant difference was found between medial and dorsolateral positions. In the division of the subthalamic nucleus into two parts, 13 contacts were located in the ventromedial part and 24 contacts were placed in the dorsolateral part. After one month, significantly greater improvement in the Non-motor Symptoms Scale for Parkinson's disease (P=0.045) was found on dorsolateral left-sided stimulation, but no significant differences between the ventromedial and dorsolateral positions were found on the right side. CONCLUSION: This study demonstrated the relationship between improvement of non-motor symptoms and the side (hemisphere, left/right) of the deep brain stimulation electrode active contact, rather than its precise location within specific parts of the subthalamic nucleus in patients treated for advanced Parkinson's disease.

Premotor Parkinson's disease: Overview of clinical symptoms and current diagnostic methods.

Parkinson's disease (PD) is characterized by typical motor symptoms. However, recent studies show several non-motor features that may precede the development of the motor symptoms of PD. The best known premotor symptoms include hyposmia, REM sleep behavior disorder (RBD), constipation, and depression; other symptoms are excessive daytime somnolence, orthostatic hypotension and symptomatic hypotension, erectile or urinary dysfunction, musculoskeletal symptoms, pain, and global cognitive deficit. In this review, we summarize currently available diagnostic methods for these symptoms. We also briefly summarize neuroimaging, polyneuropathy, peripheral markers, and cerebrospinal fluid biomarkers that may be used in the early diagnosis of PD.

Cerebrospinal Fluid Levels of Chromogranin A in Parkinson's Disease and Multiple System Atrophy.

BACKGROUND: Chromogranin A (CgA) and other peptides from the chromogranin-secretogranin family have been recently studied as potential biomarkers of various neurodegenerative diseases, including Parkinson's disease (PD). METHODS: We measured CgA in the cerebrospinal fluid (CSF) of 119 PD patients, 18 multiple system atrophy (MSA) patients, and 31 age-matched controls. We also correlated the values with disease duration and levodopa dose equivalent. RESULTS: In the PD patients, CSF CgA tended to be lower than the control group (median 124.5 vs. 185.2 µg/L; p = 0.057); however, the results did not reach statistical significance. CSF CgA levels in MSA were significantly lower compared to the control group (median 104.4 vs. 185.2; p = 0.014). There was no significant difference in CSF CgA between PD and MSA patients (p = 0.372). There was no association between CSF CgA and disease duration or levodopa dose equivalent in PD or in MSA. CONCLUSIONS: We observed a tendency toward lower CSF CgA levels in both PD and MSA compared to the control group; however, the difference reached statistical significance only in MSA. Based on these results, CgA may have potential as a biomarker in PD and MSA, but further studies on larger numbers of patients are needed to draw conclusions.

Deep Brain Stimulation Effects on Gait Pattern in Advanced Parkinson's Disease Patients.

BACKGROUND: Gait disturbance accompanies many neurodegenerative diseases; it is characteristic for Parkinson's disease (PD). Treatment of advanced PD often includes deep brain stimulation (DBS) of the subthalamic nucleus. Regarding gait, previous studies have reported non-significant or conflicting results, possibly related to methodological limitations. OBJECTIVE: The objective of this prospective study was to assess the effects of DBS on biomechanical parameters of gait in patients with PD. METHODS: Twenty-one patients with advanced PD participated in this prospective study. Gait was examined in all patients using the Zebris FDM-T pressure-sensitive treadmill (Isny, Germany) before DBS implantation and after surgery immediately, further immediately after the start of neurostimulation, and 3 months after neurostimulator activation. We assessed spontaneous gait on a moving treadmill at different speeds. Step length, stance phase of both lower limbs, double-stance phase, and cadence were evaluated. RESULTS: In this study, step length increased, allowing the cadence to decrease. Double-stance phase duration, that is, the most sensitive parameter of gait quality and unsteadiness, was reduced, in gait at a speed of 4.5 km/h and in the narrow-based gaits at 1 km/h (tandem gait), which demonstrates improvement. CONCLUSION: This study suggests positive effects of DBS treatment on gait in PD patients. Improvement was observed in several biomechanical parameters of gait.

Bilateral subthalamic deep brain stimulation initial impact on nonmotor and motor symptoms in Parkinson's disease: An open prospective single institution study.

Numerous studies document significant improvement in motor symptoms in patients with Parkinson's disease (PD) after deep brain stimulation of the subthalamic nucleus (STN-DBS). However, little is known about the initial effects of STN-DBS on nonmotor domains.Our objective was to elucidate the initial effects of STN-DBS on non-motor and motor symptoms in PD patients in a 4-month follow-up.This open prospective study followed 24 patients with PD who underwent STN-DBS. The patients were examined using dedicated rating scales preoperatively and at 1 and 4 months following STN-DBS to determine initial changes in motor and nonmotor symptoms. Patients at month 1 after STN-DBS had significantly reduced the Parkinson's disease Questionnaire scores (P = .018) and Scales for Outcomes in Parkinson's disease - Autonomic scores (P = .002); these scores had increased at Month 4 after DBS-STN. Nonmotor Symptoms Scale for Parkinson's Disease had improved significantly at Month 1 (P < .001); at Month 4, it remained significantly lower than before stimulation (P = .036). There was no significant difference in The Parkinson's Disease Sleep Scaleat Month 1 and significant improvement at Month 4 (P = .026). There were no significant changes in The Female Sexual Function Index or International Index of Erectile Function. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III scores show significant improvements at Month 1 (P < .001) and at Month 4 (P < .001).STN-DBS in patients with advanced PD clearly improves not only motor symptoms, but also several domains of nonmotor functions, namely sleep, autonomic functions and quality of life quickly following the start of stimulation.

Familial, autosomal-dominant neurodegenerative parkinsonism with cognitive deterioration spanning five generations in a genetically isolated population of south-eastern Moravia, Czech Republic.

BACKGROUND: An epidemiological study conducted over four years revealed increased prevalence of neurodegenerative parkinsonism in a small, isolated region (10 villages, with a combined population of 8664, with approx. 2927 over 50 years of age) of south-eastern Moravia, Czech Republic. The aim of this study was to obtain more detailed information on the medical history of the relatives of individuals with confirmed parkinsonism in an isolated rural population in south-eastern Moravia, Czech Republic. METHODS: We did detailed genealogical research on the families of all inhabitants with confirmed parkinsonism and compiled the pedigrees. These were modified on the basis of information from a consecutive door-to-door survey and local municipal and church registers. RESULTS: In the first stage, three large pedigrees with a familial occurrence of parkinsonism were found; two originated in one of the region's villages. In the second stage, these two pedigrees were combined into one large family tree. CONCLUSIONS: The high prevalence of parkinsonism in the researched area is caused by the familial aggregation of parkinsonism that was found in two large family trees. This is probably the result of the genetic isolation of the regional population due to the very low migration rate of its inhabitants to neighboring regions in the last two centuries.

Treatment of camptocormia with continuous subcutaneous infusions of apomorphine: 1-year prospective pilot study.

Camptocormia is defined as a marked dystonic flexion of the trunk in the sagittal plane. Camptocormia responds poorly to botulinum toxin injections, manipulation with dopaminergic treatment, and deep brain stimulation. We designed a prospective pilot study to assess the effect of apomorphine infusions on camptocormia. Five patients were enrolled. All five patients responded well to this treatment. The fact that camptocormia responds so well to apomorphine may be explained by the sustained stimulation of the ventrolateral striatal D1 receptors, alleviating this type of dystonia.