Amplitude and velocity dependence of patellar pendulum triggered by T reflex in Parkinson’s rigidity

Neurological Sciences - The relation between increase of tonus and joint movement velocity is controversial in Parkinson’s rigidity. It is accepted that the increase of tonus in rigidity is...     

The effect of real and virtual visual cues on walking in Parkinson’s disease

Patients with Parkinson’s disease (PwPD) have a slow, shuffling gait, marked by sporadic freezing of gait (FoG) during which effective stepping ceases temporarily. As these gait problems are not commonly improved by medical and surgical treatments, alternative approaches to manage these problems have been adopted. The aim of this study was to evaluate the effect of real and virtual visual cues on walking in PD. We assessed 26 mid-stage PwPD, on and off medication, on a laboratory-based walking task which simulated real world challenges by incorporating FoG triggers and using appropriate placebo conditions. Cueing interventions were presented via virtual reality glasses (VRG rhythmic, visual flow and static placebo cues), and as transverse lines (TL) on the walkway. Objective measures of gait (task completion time; velocity, cadence, stride length; FoG frequency) and self-rated fear of falling (FoF) were recorded. Cueing intervention affected task completion time only off medication. Whereas placebo VRG cues provided no improvement in walking, visual flow VRG cues marginally reduced the task completion time. TL on the floor elicited more substantial improvements in gait with reduced cadence, increased stride length and reduced FoG frequency. VRG rhythmic cueing impaired overall walking. Notably, a final no-intervention condition yielded quicker task completion, greater walking velocity, increased stride length and less frequent FoG. Although the VRG produced modest improvements only in the visual flow condition, their flexibility is an advantage. These results endorse the use of TL and justify further testing and customisation of VRG cues for individual PwPD.     

Beyond tremor and rigidity: non-motor features of Parkinson’s disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease and primarily considered as a movement disorder defined by the presence of motor symptoms, such as bradykinesia, tremor and rigidity. However, it is nowadays widely accepted that PD is associated with a wide variety of non-motor features, which affect the vast majority of patients during the course of the disease and may even precede the onset of motor symptoms. The spectrum of these non-motor disturbances is very broad and comprises neuropsychiatric conditions, such as depression, dementia and hallucinations, as well as autonomic, sensory and sleep disorders. Physicians need to be aware of these non-motor features, since they have substantial impact on the health-related quality of life of PD patients, even ahead of motor symptoms. This article aims to provide an overview of frequently observed non-motor features in PD and discusses prospects and limitations of currently available options for symptomatic treatment of these disturbances.     

The effect of Parkinson’s disease subgroups on verbal and nonverbal fluency

Background. Parkinson’s disease (PD) leads to deficits in executive function, including verbal and nonverbal fluency, as a result of compromised frontostriatal circuits. It is unknown whether deficits in verbal and nonverbal fluency in PD are driven by certain subgroups of patients, or how strategy use may facilitate performance. Participants. Sixty-five nondemented individuals with PD, including 36 with right-body onset (RPD; 20 with tremor as their initial symptom, 16 nontremor) and 29 with left-body onset (LPD; 14 with tremor as their initial symptom, 15 nontremor), and 52 normal control participants (NC) took part in the study. Measurements. Verbal fluency was assessed using the FAS and Animals tests. Nonverbal fluency was assessed using the Ruff Figural Fluency Test. Results. Both RPD and LPD were impaired in generating words and in using clustering and switching strategies on phonemic verbal fluency, whereas different patterns of impairment were found on nonverbal fluency depending on the interaction of side of onset and initial motor symptom (tremor vs. nontremor). Strategy use correlated with number of correct responses on verbal fluency in LPD, RPD, and NC. By contrast, on nonverbal fluency, strategy use correlated with correct responses for RPD and LPD, but not for NC. Conclusion. Our findings demonstrate the importance of considering subgroups in PD and analyzing subcomponents of verbal and nonverbal fluency (correct responses, errors, and strategies), which may depend differently on the integrity of dorsolateral prefrontal cortex, inferior frontal cortex, and anterior cingulate cortex.     

Pergolide effect on cognitive functions in early-mild Parkinson’s disease

Summary. In the present study, we evaluated the effect of pergolide, a mixed D1/D2 agonist, on cognitive function in mild Parkinsons disease (PD). After a two-week wash-out phase, twenty patients with a Hoehn and Yahr score 2.5 entered a 16-week, cross-over study in which the order of administration of pergolide or 1-dopa was randomly assigned. Cognitive assessment was performed after the wash-out phase and repeated after eight weeks (before patients were switched to the other drug) and at the end of the study. There were no significant differences in test scores among the three experimental modalities (off-treatment vs. l-dopa, off-treatment vs. pergolide, pergolide vs. l-dopa).In another cohort of comparably mild PD patients we had previously demonstrated that pramipexole, a mixed D2/D3 agonist, slightly but significantly worsened verbal fluency in comparison to l-dopa; moreover, pramipexole impaired short term verbal memory and attentional-executive functions in comparison to both l-dopa and the off-treatment condition. Taken together, these findings suggest that dopamine agonists may influence cognition in PD according to their pharmacological characteristics. Unlike the D2/D3 agonist pramipexole, pergolide and l-dopa, both of which stimulate D1- and D2-receptor subtypes, do not appear to impair cognitive function.     

The effect of dopamine replacement therapy on haptic sensitivity in Parkinson’s disease

Increasing evidence indicates that processing of proprioceptive information is altered in Parkinson’s disease (PD), leading to reduced kinaesthetic and haptic sensitivity. However, there is inconclusive evidence whether dopamine replacement therapy (DRT) ameliorates or worsens kinaesthetic and haptic function in PD. For assessing perceptual function, we employed a task that did not require active motion or stressed working memory function, which may become impaired in PD. A group of mild to moderate stage PD patients (n = 9) and a group of age-matched healthy controls participated in this study. Without vision, a subject’s hand was moved by a robotic manipulandum along the contours of a small “virtual box” (5 × 15 cm). At the end of each trial, they indicated whether the contour was “curved” or “straight”. PD patients were tested ON and OFF antiparkinsonian medication. Psychophysical detection thresholds were determined (curvature at which subjects correctly perceived a curved contour at the 75% level). Compared to the control group, thresholds were elevated by 55% in the PD patient group. During the ON medication state, the mean detection threshold of the patient group was reduced by 15% (ON: 4.71 m⁻¹; OFF: 5.42 m⁻¹). Increases in curvature sensitivity were highly correlated with improved clinical scores of motor function (r = 0.74) with more affected patients showing higher gains in sensitivity as the result of DRT (r = 0.80). This report documents that DRT can ameliorate haptic and kinaesthetic function in patients with mild to moderate PD, suggesting that DRT can have beneficial effects on perceptual function.     

The neuroprotective effect of dental pulp cells in models of Alzheimer’s and Parkinson’s disease

Aim of the present study was to investigate the neuroprotective effect of dental pulp cells (DPCs) in in vitro models of Alzheimer and Parkinson disease. Primary cultures of hippocampal and ventral mesencephalic neurons were treated for 24 h with amyloid beta (Aβ_1–42) peptide 1–42 and 6-OHDA, respectively. DPCs isolated from adult rat incisors were previously cultured in tissue culture inserts and added to the neuron cultures 2 days prior to neurotoxin treatment. Cell viability was assessed by the MTT assay. The co-culture with DPCs significantly attenuated 6-OHDA and Aβ_1–42-induced toxicity in primary cultures of mesencephalic and hippocampal neurons, and lead to an increase in neuronal viability in untreated cultures, suggesting a neurotrophic effect in both models. Furthermore, human dental pulp cells expressed a neuronal phenotype and produced the neurotrophic factors NGF, GDNF, BDNF, and BMP2 shown by microarray screening and antibody staining for the representative proteins. DPCs protected primary neurons in in vitro models of Alzheimer’s and Parkinson’s disease and can be viewed as possible candidates for studies on cell-based therapy. C. Apel and O. V. Forlenza: both authors contributed equally to the work.     

The effect of orexin-A on motor and cognitive functions in a rat model of Parkinson’s disease

Objective: The aim of this study was to evaluate the effect of orexin-A (OX-A) and the orexin-1 receptor antagonist SB-334867 (SB) on motor and cognitive functions in a rat model of Parkinson’s disease. Methods: Parkinson was induced by intracerebroventricular (i.c.v) injection of 6- hydroxydopamine (6-OHDA) (200 μg/rat). 72 h later, the treatment was initiated by i.c.v administration of SB (30 nmol/rat) and/or OX-A (0.3 nmol/rat) for 10 days. Motor functions were monitored using rotarod and hanging tests. Cognitive function was assessed by passive avoidance test (Shuttle box). Results: OX-A administration in 6-OHDA treated rats remarkably increased the time which animals run on rod (in rotarod test) and also the latency to fall (in hanging test) (P < 0.01 and P < 0.001, respectively). Conversely, administration of SB in 6-OHDA-treated rats decreased the mentioned indices (P < 0.05 for latency to fall). Administration of agonist and/or antagonist of orexin-1 receptors had no significant effect on 6-OHDA induced cognitive impairment in rats. Conclusion: Results of this study suggest that the orexinergic system might be involved in sensory-motor deficits of Parkinson’s disease.     

Pedunculopontine tegmental Nucleus-evoked prepulse inhibition of the blink reflex in Parkinson’s disease

ObjectiveTo investigate the effects on the blink reflex (BR) of single stimuli applied to the pedunculopontine tegmental nucleus (PPTg).MethodsThe BR was evoked by stimulating the supraorbital nerve (SON) in fifteen patients suffering from idiopathic Parkinson’s disease (PD) who had electrodes monolaterally or bilaterally implanted in the PPTg for deep brain stimulation (DBS). Single stimuli were delivered to the PPTg through externalized electrode connection wires 3–4 days following PPTg implantation.ResultsPPTg stimuli increased the latency and reduced duration, amplitude and area of the R2 component of the BR in comparison to the response recorded in the absence of PPTg stimulation. These effects were independent of the side of SON stimulation and were stable for interstimulus interval (ISI) between PPTg prepulse and SON stimulus from 0 to 110 ms. The PPTg-induced prepulse inhibition of the BR was bilaterally present in the brainstem. The R1 component was unaffected.ConclusionsThe prepulse inhibition of the R2 component may be modulated by the PPTg.SignificanceThese findings suggest that abnormalities of BR occurring in PD may be ascribed to a reduction of basal ganglia-mediated inhibition of brainstem excitability.     

Independent effect of neurogenic orthostatic hypotension on mild cognitive impairment in Parkinson’s disease

Clinical Autonomic Research - Orthostatic hypotension (OH) is an associative or causative factor of cognitive impairment in Parkinson’s disease (PD). However, the association between mild...     

The effect of l-Dopa administration on pursuit ocular movements in suspected Parkinson’s disease

The objective of this study is to evaluate pursuit ocular movements (POM) by using a vision-based non-intrusive eye tracker, in patients with suspected Parkinson’s disease (PD), before and after l-Dopa administration. We studied ten patients with suspected diagnosis of idiopathic PD. We compared POM values to those of a group of normal controls (NC), and evaluated them before and after l-Dopa administration. Unified Parkinson’s Disease Rating Scale (UPDRS) motor subscores improved significantly (p = 0.001). At baseline, values of POM were lower in suspected PD patients than in NC (p = 0.01). One hour after l-Dopa administration, POM values correlated with UPDRS motor subscore (p = 0.01). We used a recent method, a new vision-based non-intrusive eye tracker, previously described, which can be proposed as a possible tool for supporting the diagnosis of PD in association with levodopa test, as an add-on to the UPDRS score.     

Parkinson’s disease in patients and obligate carriers of Gaucher disease

BackgroundGaucher disease is an autosomal recessive disorder caused by glucocerebrosidase gene mutations. Accumulating evidence from several Parkinson’s disease cohorts of varying ethnicities suggests that glucocerebrosidase mutations even in the heterozygous state (carriers) may be a susceptibility factor for Parkinson’s. Very few studies have analyzed the frequency of Parkinson’s in carriers and individuals with Gaucher disease.ObjectiveTo determine frequency of Parkinson’s in patients with Gaucher disease and obligate carriers of glucocerebrosidase mutations and compare it with a control group.MethodsA questionnaire was completed by 100 Ashkenazi Jewish Gaucher patients followed at our center and 109 ethnicity-matched controls with no personal or family history of Gaucher disease.ResultsFrequency of Parkinson’s was higher in Gaucher patients (8/100) than in controls (0/109; P = 0.0024). Frequency of Parkinson’s in obligate carriers (11/200) was higher than controls (6/218), but the difference was not statistically significant (P = 0.215). Average age of onset of Parkinson’s was earlier in Gaucher patients (57.2) than the general population and in obligate carriers (60) when compared with controls (76.8; P = 0.01). The L444P genotype was more frequent in Gaucher patients who reported a parent with Parkinson’s (36.40%) than those who did not (4.50%).ConclusionOur study suggests that the risk for developing Parkinson’s may be higher in affected versus carriers of glucocerebrosidase mutations and suggests that L444P may pose a higher risk of developing Parkinson’s than other mutations. It also confirms previous findings that the age of onset of Parkinson’s associated with glucocerebrosidase mutations is earlier than in the general population.     

Depression and apathy in Parkinson’s disease

This article provides an update on depression and apathy in Parkinson’s disease (PD), both of which are common but often misunderstood. The diagnosis of depression in PD can be challenging and we still do not have solid evidence on which to base our treatment decisions. Apathy is most commonly seen in the setting of dementia or depression but emerging evidence suggests that it may be a core feature of PD. There are conflicting reports about the effects of deep brain stimulation (DBS) on mood and apathy, but studies suggest that at least some patients may develop depression and apathy after the procedure. Although we are making strides toward a better understanding of depression and apathy in PD, it is clear that more research is needed about these non-motor features.     

Beneficial effect of 24-month bilateral subthalamic stimulation on quality of sleep in Parkinson’s disease

Journal of Neurology - Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and sleep symptoms in Parkinson’s disease (PD). However, the long-term...     

Impact of drooling in Parkinson’s disease

Drooling is a well known problem in patients with Parkinson's disease (PD). The aim of this study was to investigate the severity and consequences of drooling in PD. A comprehensive drooling questionnaire was sent to 105 PD outpatients, who had volunteered drooling during a previous questionnaire (n = 216). Among 63 patients who responded and confirmed drooling, 27% experienced severe saliva loss. Social and emotional consequences were reported by 17% to 77% of patients, and significantly more often by those with severe drooling. We conclude that drooling is a frequent, disabling and apparently undertreated symptom of PD. History taking ought to be detailed and specific to understand the full impact of drooling for an individual patient. Therapeutic options should be evaluated more intensively.     

Pharmacotherapy of Parkinson’s disease in Germany

Treatment standards or guidelines have been developed for most features of Parkinson’s disease (PD). However, data on the actual treatment that is put into practice are scarce. In 2000, a nationwide survey on the topic of sudden onset of sleep (SOS) in PD was initiated among the members of the German patient support group (deutsche Parkinson–Vereinigung, dPV). A part of this mailed questionnaire survey covering the antiparkinsonian and concomitant medication of the participants is presented here. This study analyses data sets from more than 6,500 PD patients. The mean dopaminergic dose was equivalent to 599 ± 387 mg levodopa/die. The most frequently administered drugs were levodopa (94.2 %), dopamine agonists (DA) (71.7 %), amantadine (40.1 %), selegiline (27.6 %), entacapone (20.4 %), budipine (12.3 %), and anticholinergics (11.8 %). Costs of pharmacotherapy were estimated to be approximately € 399 million/year in Germany. PD drug therapy in general strongly depended on age, disease duration, and the level of care. The treatment guidelines were apparently not consistently followed underlining the need for their continuous propagation throughout the medical community. In addition our data suggest that non–motor symptoms in PD are not adequately treated and that concomitant sedative medication contributes to the occurrence of SOS.     

Impact of the LSVT on vowel articulation and coarticulation in Parkinson’s disease

The purpose of this study was to investigate the impact of the Lee Silverman Voice Treatment (LSVT®) on vowel articulation and consonant–vowel (C–V) coarticulation in dysarthric speakers with Parkinson’s disease (PD). Nine Quebec French speakers diagnosed with idiopathic PD underwent the LSVT®. Speech characteristics were compared before and after treatment. Vowel articulation was measured using acoustic vowel space and calculated with the first (F1) and second formant (F2) of the vowels /i/, /u/ and /a/. C–V coarticulation was measured using locus equations, an acoustic metric based on the F2 transitions within vowels in relation to the preceding consonant. The relationship between these variables, speech loudness and vowel duration was also analysed. Results showed that vowel contrast increased in F1/F2 acoustic space after administration of the LSVT®. This improvement was associated with the gain in speech loudness and longer vowel duration. C–V coarticulation patterns between consonant contexts showed greater distinctiveness after the treatment. This improvement was associated with the gain in speech loudness only. These results support the conclusions of previous studies investigating the relationship between the LSVT®, speech loudness and articulation in PD. These results expand clinical understanding of the treatment and indicate that loud speech changes C–V coarticulation patterns. Clinical applications and theoretical considerations are discussed.