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Parkinson's Disease and Other Movement Disorders [keywords]
- Applause sign in clinically overlapping diseases: A case of TDP-43 proteinopathy. [LETTER]
- Parkinsonism Relat Disord 2013 May 13.
- Delusional misidentification syndrome and other unusual delusions in advanced Parkinson's disease. [JOURNAL ARTICLE]
- Parkinsonism Relat Disord 2013 May 13.
BACKGROUND:Unusual delusional syndromes are rare protean diseases with speculative etiopathogenic mechanisms.
METHODS:Seven consecutive patients with advanced PD were evaluated over a 15-year period at the Movement Disorders Unit in the Neurology Service, Hospital de Clínicas, Federal University of Paraná, and the Paraná State Parkinson's Patients Association.
RESULTS:We describe advanced Parkinson's disease patients presenting with unusual delusional syndromes, including cases of Ekbom, Othello, Capgras' and Diogenes syndromes, reduplicative paramnesia and mirrored-self misidentification.
CONCLUSION:There are a few isolated reports of unusual neuropsychiatric disorders in patients with PD. We believe that these syndromes associated with advanced PD in elderly patients presenting with cognitive impairment and polypharmacy are probably often underestimated. Neurologists should be aware for these rare and treatable conditions.
- Flu-like Symptoms and Associated Immunological Response Following Therapy with Botulinum Toxins. [JOURNAL ARTICLE]
- Neurotox Res 2013 May 16.
We aimed to define the frequency and risk factors associated with flu-like symptoms (FLS) and other systemic symptoms following treatment with botulinum toxins (BoNT) and correlate them with the immunological response as determined by blood cytokines. The study involved prospective clinical and serological evaluation for cytokine analysis in patients receiving BoNT for movement disorders. We interviewed 218 patients about FLS following BoNT injections and prospectively studied 117 patients (females 67.5 %; mean age 59.74 ± 12.39 years) treated with BoNT in a total of 143 treatment cycles. While no patient reported any FLS at baseline, the symptom complex was subsequently reported in 19 patients (16.3 %) and in 20 (14 %) treatment cycles, with at least one systemic symptom reported in 49 (42 %) patients in 59 (41.3 %) treatment cycles. FLS and at least one symptom were reported more frequently by women (P = 0.006 and P = 0.049, respectively) and by younger patients: 55.6 versus 61.7 years (P = 0.022). Although the symptoms were usually considered mild, they were rated as moderate to serious after 18 (12 %) cycles. The following interleukins showed increased levels at 7-10 days after the BoNT injections: IL-1β, IL-8, GROα, eotaxin, MCP-1 and 2, RANTES, TARC, and inducible protein 10 (IP10), but only the latter showed significantly increased levels in patients with FLS: 69 versus 3 pg/ml (P = 0.007). FLS and other systemic symptoms occur after about 14 % of treatment visits in patients receiving BoNT. IP10 levels correlate with the presence and severity of FLS.
- Variability in neuronal expression of dopamine receptors and transporters in the substantia nigra. [JOURNAL ARTICLE]
- Mov Disord 2013 May 14.
Parkinson's disease (PD) patients have increased susceptibility to impulse control disorders. Recent studies have suggested that alterations in dopamine receptors in the midbrain underlie impulsive behaviors and that more impulsive individuals, including patients with PD, exhibit increased occupancy of their midbrain dopamine receptors. The cellular location of dopamine receptor subtypes and transporters within the human midbrain may therefore have important implications for the development of impulse control disorders in PD. The localization of the dopamine receptors (D1-D5) and dopamine transporter proteins in the upper brain stems of elderly adult humans (n = 8) was assessed using single immunoperoxidase and double immunofluorescence (with tyrosine hydroxylase to identify dopamine neurons). The relative amount of protein expressed in dopamine neurons from different regions was assessed by comparing their relative immunofluorescent intensities. The midbrain dopamine regions associated with impulsivity (medial nigra and ventral tegmental area [VTA]) expressed less dopamine transporter on their neurons than other midbrain dopamine regions. Medial nigral dopamine neurons expressed significantly greater amounts of D1 and D2 receptors and vesicular monoamine transporter than VTA dopamine neurons. The heterogeneous pattern of dopamine receptors and transporters in the human midbrain suggests that the effects of dopamine and dopamine agonists are likely to be nonuniform. The expression of excitatory D1 receptors on nigral dopamine neurons in midbrain regions associated with impulsivity, and their variable loss as seen in PD, may be of particular interest for impulse control. © 2013 Movement Disorder Society.
- Could sensory mechanisms be a core factor that underlies freezing of gait in Parkinson's disease? [Journal Article]
- PLoS One 2013; 8(5):e62602.
The main objective of this study was to determine how manipulating the amount of sensory information available about the body and surrounding environment influenced freezing of gait (FOG), while walking through a doorway. It was hypothesized that the more limited the sensory information, the greater the occurrence of freezing of gait. Nineteen patients with Parkinsoǹs disease who experience freezing of gait (PD-FOG) walked through a doorway or into open space in complete darkness. The three doorway conditions included: (i) FRAME (DARK) - walking through the remembered door frame; (ii) FRAME - walking through the door with the door frame illuminated; (iii) FRAME+BODY - walking through the door (both the door and the limbs illuminated). Additionally, two conditions of walking away from the doorway included: (iv) NO FRAME (DARK) - walking into open space; (v) NO FRAME+BODY - walking into open space with the limbs illuminated, to evaluate whether perception (or fear) of the doorway might account for FOG behaviour. Key outcome measures included: the number of freezing of gait episodes recorded, total duration of freezing of gait, and the percentage of time spent frozen. Significantly more freezing of gait episodes occurred when participants walked toward the doorway in complete darkness compared to walking into open space (p<0.05). Similar to previous studies, velocity (p<0.001) and step length (p<0.0001) significantly decreased when walking through the door in complete darkness, compared to all other conditions. Significant increases in step width variability were also identified but only when walking into open space (p<0.005). These results support the notion that sensory deficits may have a profound impact on freezing of gait that need to be carefully considered.
- Microfluidic-based Electrotaxis for On-demand Quantitative Analysis of Caenorhabditis elegans' Locomotion. [Journal Article]
- J Vis Exp 2013; (75)
The nematode Caenorhabditis elegans is a versatile model organism for biomedical research because of its conservation of disease-related genes and pathways as well as its ease of cultivation. Several C. elegans disease models have been reported, including neurodegenerative disorders such as Parkinson's disease (PD), which involves the degeneration of dopaminergic (DA) neurons (1). Both transgenes and neurotoxic chemicals have been used to induce DA neurodegeneration and consequent movement defects in worms, allowing for investigations into the basis of neurodegeneration and screens for neuroprotective genes and compounds (2,3). Screens in lower eukaryotes like C. elegans provide an efficient and economical means to identify compounds and genes affecting neuronal signaling. Conventional screens are typically performed manually and scored by visual inspection; consequently, they are time-consuming and prone to human errors. Additionally, most focus on cellular level analysis while ignoring locomotion, which is an especially important parameter for movement disorders. We have developed a novel microfluidic screening system (Figure 1) that controls and quantifies C. elegans' locomotion using electric field stimuli inside microchannels. We have shown that a Direct Current (DC) field can robustly induce on-demand locomotion towards the cathode ("electrotaxis") (4). Reversing the field's polarity causes the worm to quickly reverse its direction as well. We have also shown that defects in dopaminergic and other sensory neurons alter the swimming response (5). Therefore, abnormalities in neuronal signaling can be determined using locomotion as a read-out. The movement response can be accurately quantified using a range of parameters such as swimming speed, body bending frequency and reversal time. Our work has revealed that the electrotactic response varies with age. Specifically, young adults respond to a lower range of electric fields and move faster compared to larvae (4). These findings led us to design a new microfluidic device to passively sort worms by age and phenotype (6). We have also tested the response of worms to pulsed DC and Alternating Current (AC) electric fields. Pulsed DC fields of various duty cycles effectively generated electrotaxis in both C. elegans and its cousin C. briggsae (7). In another experiment, symmetrical AC fields with frequencies ranging from 1 Hz to 3 KHz immobilized worms inside the channel (8). Implementation of the electric field in a microfluidic environment enables rapid and automated execution of the electrotaxis assay. This approach promises to facilitate high-throughput genetic and chemical screens for factors affecting neuronal function and viability.
- Initial Treatment of Parkinson's Disease: An Update. [JOURNAL ARTICLE]
- Curr Treat Options Neurol 2013 May 4.
OPINION STATEMENT: This is an update to an article published in this journal in 2006, which covered the initial treatment of Parkinson's disease (PD). In this update, we review new research into symptomatic treatments, potential disease modifying ("neuroprotective") agents, and evidence-based reviews of current treatment. We discuss the usage of the MAO-B inhibitors, including the controversy surrounding the possible neuroprotective effects of rasagiline. Usage of extended release formulations of pramipexole and ropinirole, as well as the transdermal dopamine agonist rotigotine, are reviewed. Side effects of the dopamine agonists are discussed, including the cardiac side effects of ergot-derived dopamine agonists, and the impulse control disorders associated with the dopamine agonists. The use of zonisamide as an agent for PD tremor is reviewed. We touch on the clinical research into the benefits of exercise in PD, and briefly review some of the current studies for new formulations of levodopa and other medications and treatments with novel mechanisms of action.
- Rasagiline meta-analysis: a spotlight on clinical safety and adverse events when treating Parkinson's disease. [JOURNAL ARTICLE]
- Expert Opin Drug Saf 2013 May 2.
Introduction: Rasagiline (Azilect, AGN 1135) is a selective irreversible inhibitor of monoamine oxidase B (MAO-B). MAO-B regulates the brain concentrations of important neurotransmitters that are related to movement, emotion, and cognition. Oral rasagiline, as monotherapy or as adjunctive therapy to levodopa, was effective in the symptomatic treatment of adult patients with Parkinson's disease participating in double-blind, placebo-controlled, international studies. Areas covered: This article reviews the reported adverse effects of rasagiline. A MEDLINE search was performed for all articles from 1990 to present, which reported any adverse effects from rasagiline or related references. We conducted an analysis of the adverse effects of rasagiline based on the reported clinical studies. Furthermore, we compared the incidence of adverse events in clinical trials for rasagiline and placebo. Expert opinion: Among the most frequently reported adverse effects for rasagiline as monotherapy are headache, dizziness, and insomnia. Depression, dizziness, somnolence, and other sleep disorders are reported when used in combination therapy. Our analysis demonstrates that the most frequently reported adverse effects in trials did not occur more often with rasagiline than placebo. In conclusion, rasagiline is a well-tolerated MAO-B inhibitor that may help to achieve the desired level of clinical benefit in Parkinson's disease.
- Diagnosis and treatment of impulse control disorders in patients with movement disorders. [Journal Article]
- Ther Adv Neurol Disord 2013 May; 6(3):175-88.
Impulse control disorders are a psychiatric condition characterized by the failure to resist an impulsive act or behavior that may be harmful to self or others. In movement disorders, impulse control disorders are associated with dopaminergic treatment, notably dopamine agonists (DAs). Impulse control disorders have been studied extensively in Parkinson's disease, but are also recognized in restless leg syndrome and atypical Parkinsonian syndromes. Epidemiological studies suggest younger age, male sex, greater novelty seeking, impulsivity, depression and premorbid impulse control disorders as the most consistent risk factors. Such patients may warrant special monitoring after starting treatment with a DA. Various individual screening tools are available for people without Parkinson's disease. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease has been developed specifically for Parkinson's disease. The best treatment for impulse control disorders is prevention. However, after the development of impulse control disorders, the mainstay intervention is to reduce or discontinue the offending anti-Parkinsonian medication. In refractory cases, other pharmacological interventions are available, including neuroleptics, antiepileptics, amantadine, antiandrogens, lithium and opioid antagonists. Unfortunately, their use is only supported by case reports, small case series or open-label clinical studies. Prospective, controlled studies are warranted. Ongoing investigations include naltrexone and nicotine.
- Quality of life, health status and caregiver burden in Parkinson's disease: relationship to executive functioning. [JOURNAL ARTICLE]
- Int J Geriatr Psychiatry 2013 Apr 29.