Trastornos del sueño en la enfermedad de Parkinson y otros trastornos del movimiento

Neurodegenerative processes with movement disorders is predominant features show a high incidence of sleep alterations at some point in their evolution. The degeneration of structures responsible for maintaining the sleep-wakefulness cycles and the architecture of sleep could be at their root. Other factors like the drugs employed in the treatment of motor problems, the limitations to movement, etc., aggravate the problem. Although, at present, there is no medical therapy able to restore the defects derived from the degeneration of the key structures of sleep, an individual analysis of the coadyuvant factors in each patient could help to improve these problems. In this article we describe the main sleep disorders in Parkinson’s disease and other degenerative diseases such as multi-system atrophies or progressive supranuclear paralysis

Revisión crítica de la estimulación subtalámica en la enfermedad de Parkinson

The authors critically review subthalamic nucleus (STN) stimulation for Parkinson's disease (PD) at long follow-up (3-5 years). Subthalamic stimulation induce a significant improvement during the "off" medication in the assessment motor score UPDRS (Unified Parkinson Disease Rating Scale) 3-5 years after surgery. Results show that the benefits obtained in tremor, rigidity, bradykinesia, dyskinesias induced by medication and levodopa reduction are significantly maintained during long term. The improvement in other clinical signs as gait and postural stability at long follow-up are not maintained comparing with the benefits obtained one year after surgery. A high percentage of patients show a cognitive disturbance during the follow-up period that may be correlated with the disease progression. The conclusion is that bilateral STN stimulation is an effective treatment for PD patients at long term but it should be considered earlier in the course of P

Functional correlates of response inhibition in impulse control disorders in Parkinson’s disease

Impulse control disorder is a prevalent side-effect of Parkinson’s disease (PD) medication, with a strong negative impact on the quality of life of those affected. Although impulsivity has classically been associated with response inhibition deficits, previous evidence from PD patients with impulse control disorder (ICD) has not revealed behavioral dysfunction in response inhibition. In this study, 18 PD patients with ICD, 17 PD patients without this complication, and 15 healthy controls performed a version of the conditional Stop Signal Task during functional magnetic resonance imaging. Whole-brain contrasts, regions of interest, and functional connectivity analyses were conducted. Our aim was to investigate the neural underpinnings of two aspects of response inhibition: proactive inhibition, inhibition that has been prepared beforehand, and restrained inhibition, inhibition of an invalid inhibitory tendency. We observed that, in respect to the other two groups, PD patients with ICD exhibited hyperactivation of the stopping network bilaterally while performing proactive inhibition. When engaged in restrained inhibition, they showed hyperactivation of the left inferior frontal gyrus, an area linked to action monitoring. Restrained inhibition also resulted in changes to the functional co-activation between inhibitory regions and left inferior parietal cortex and right supramarginal gyrus. Our findings indicate that PD patients with ICD completed the inhibition task correctly, showing altered engagement of inhibitory and attentional areas. During proactive inhibition they showed bilateral hyperactivation of two inhibitory regions, while during restrained inhibition they showed additional involvement of attentional areas responsible for alerting and orientin

Terapia celular “neuro-restauradora” en la enfermedad de Parkinson: un debate pendiente

Existe en la actualidad un gran entusiasmo sobre las perspectivas derivadas de la denominada terapia celular en la enfermedad de Parkinson. Este entusiasmo ha sobrepasado la esfera de la comunidad médica, llegando hasta el público general, y se ha venido alimentando de un considerable debate ético y político, hurtándose en todo momento la necesidad de un análisis realmente científico sobre las cualidades y limitaciones reales del tratamiento con células madre en las enfermedades neurodegenerativas. La enfermedad de Parkinson con frecuencia se observa desde una perspectiva simplista, como una mera neurodegeneración de la vía dopaminérgica nigroestriada, punto de vista bajo el que se colocan diferentes diseños tendentes a reemplazar la falta de dopamina en el estriado, mediante el empleo de distintos tipos de terapia celular. En este sentido, es necesario señalar por un lado la naturaleza multisistémica y generalizada de la enfermedad, y por otro lado el carácter progresivo del proceso neurodegenerativo de la enfermedad de Parkinson. Bajo este enfoque, pretender que el mero reemplazo de la dopamina estriatal mediante terapia celular sustitutiva, pueda corregir el carácter generalizado y progresivo de la enfermedad es una aspiración quimérica, que únicamente contribuye a generar expectativas infundadas en el público general. Este artículo pretende argumentar desde un punto de vista puramente científico las dudas sobre las expectativas creadas con estos nuevos diseños terapéuticos.At present there is great enthusiasm over the perspectives deriving from so-called cell therapy in Parkinson’s disease. This enthusiasm has spread beyond the ambit of the medical community, reaching the general public, and has been fuelled by a considerable ethical and political debate, sidestepping the need for a really scientific analysis of the real qualities and limitations of treatment with stem-cells in neurodegenerative diseases. Parkinson’s disease is frequently observed from a simplistic perspective, as a mere neurodegeneration of the nigrostriatal dopaminergic pathway. This viewpoint encompasses different designs that tend to replace the lack of dopamine in the striatum through the use of different types of cell therapy. In this respect, it is important to indicate, on the one hand, the multisystemic and generalised nature of the disease and, on the other, the progressive character of the neurodegenerative process of Parkinson’s disease. With this approach, to claim that the mere replacement of striatal dopamine through replacement cell therapy can correct the generalised and progressive character of the disease is a fanciful aspiration, which can only contribute to generating unfounded expectations in the general public. This article attempts to set out from a purely scientific point of view the doubts over the expectations created by these new therapeutic designs

Functional bold MRI: advantages of the 3 T vs. the 1.5 T

We quantitatively evaluate the benefits of a higher field strength for functional brain MRI (fMRI) based on the blood oxygenation level-dependent contrast. The 3-T fMRI shows a higher sensitivity for the motor and somatosensory stimulation and more specific localization in the grey substance. The 3-T fMRI detects additional areas of activation with the motor paradigm

Using Kinect to classify Parkinson's disease stages related to severity of gait impairment

Background: Parkinson’s Disease (PD) is a chronic neurodegenerative disease associated with motor problems such as gait impairment. Different systems based on 3D cameras, accelerometers or gyroscopes have been used in related works in order to study gait disturbances in PD. Kinect has also been used to build these kinds of systems, but contradictory results have been reported: some works conclude that Kinect does not provide an accurate method of measuring gait kinematics variables, but others, on the contrary, report good accuracy results. Methods: In this work, we have built a Kinect-based system that can distinguish between different PD stages, and have performed a clinical study with 30 patients suffering from PD belonging to three groups: early PD patients without axial impairment, more evolved PD patients with higher gait impairment but without Freezing of Gait (FoG), and patients with advanced PD and FoG. Those patients were recorded by two Kinect devices when they were walking in a hospital corridor. The datasets obtained from the Kinect were preprocessed, 115 features identified, some methods were applied to select the relevant features (correlation based feature selection, information gain, and consistency subset evaluation), and different classification methods (decision trees, Bayesian networks, neural networks and K-nearest neighbours classifiers) were evaluated with the goal of finding the most accurate method for PD stage classification. Results: The classifier that provided the best results is a particular case of a Bayesian Network classifier (similar to a Naïve Bayesian classifier) built from a set of 7 relevant features selected by the correlation-based on feature selection method. The accuracy obtained for that classifier using 10-fold cross validation is 93.40%. The relevant features are related to left shin angles, left humerus angles, frontal and lateral bents, left forearm angles and the number of steps during spin. Conclusions: In this paper, it is shown that using Kinect is adequate to build a inexpensive and comfortable system that classifies PD into three different stages related to FoG. Compared to the results of previous works, the obtained accuracy (93.40%) can be considered high. The relevant features for the classifier are: a) movement and position of the left arm, b) trunk position for slightly displaced walking sequences, and c) left shin angle, for straight walking sequences. However, we have obtained a better accuracy (96.23%) for a classifier that only uses features extracted from slightly displaced walking steps and spin walking steps. Finally, the obtained set of relevant features may lead to new rehabilitation therapies for PD patients with gait problems

Involvement of the subthalamic nucleus in impulse control disorders associated with Parkinson’s disease

Behavioural abnormalities such as impulse control disorders may develop when patients with Parkinson’s disease receive dopaminergic therapy, although they can be controlled by deep brain stimulation of the subthalamic nucleus. We have recorded local field potentials in the subthalamic nucleus of 28 patients with surgically implanted subthalamic electrodes. According to the predominant clinical features of each patient, their Parkinson’s disease was associated with impulse control disorders (n = 10), dyskinesias (n = 9) or no dopaminergic mediated motor or behavioural complications (n = 9). Recordings were obtained during the OFF and ON dopaminergic states and the power spectrum of the subthalamic activity as well as the subthalamocortical coherence were analysed using Fourier transform-based techniques. The position of each electrode contact was determined in the postoperative magnetic resonance image to define the topography of the oscillatory activity recorded in each patient. In the OFF state, the three groups of patients had similar oscillatory activity. By contrast, in the ON state, the patients with impulse control disorders displayed theta-alpha (4–10 Hz) activity (mean peak: 6.71 Hz) that was generated 2–8mm below the intercommissural line. Similarly, the patients with dyskinesia showed theta-alpha activity that peaked at a higher frequency (mean: 8.38 Hz) and was generated 0–2mm below the intercommissural line. No such activity was detected in patients that displayed no dopaminergic side effects. Cortico-subthalamic coherence was more frequent in the impulsive patients in the 4–7.5 Hz range in scalp electrodes placed on the frontal regions anterior to the primary motor cortex, while in patients with dyskinesia it was in the 7.5–10 Hz range in the leads overlying the primary motor and supplementary motor area. Thus, dopaminergic side effects in Parkinson’s disease are associated with oscillatory activity in the theta-alpha band, but at different frequencies and with different topography for the motor (dyskinesias) and behavioural (abnormal impulsivity) manifestations. These findings suggest that the activity recorded in parkinsonian patients with impulse control disorders stems from the associative-limbic area (ventral subthalamic area), which is coherent with premotor frontal cortical activity. Conversely, in patients with L-dopa-induced dyskinesias such activity is recorded in the motor area (dorsal subthalamic area) and it is coherent with cortical motor activity. Consequently, the subthalamic nucleus appears to be implicated in the motor and behavioural complications associated with dopaminergic drugs in Parkinson’s disease, specifically engaging different anatomo-functional territories

The impact of silent vascular brain burden in cognitive impairment in Parkinson's disease

White matter hyperintensities (WMHs) detected by magnetic resonance imaging (MRI) of the brain are associated with dementia and cognitive impairment in the general population and in Alzheimer's disease. Their effect in cognitive decline and dementia associated with Parkinson's disease (PD) is still unclear. METHODS: We studied the relationship between WMHs and cognitive state in 111 patients with PD classified as cognitively normal (n = 39), with a mild cognitive impairment (MCI) (n = 46) or dementia (n = 26), in a cross-sectional and follow-up study. Cognitive state was evaluated with a comprehensive neuropsychological battery, and WMHs were identified in FLAIR and T2-weighted MRI. The burden of WMHs was rated using the Scheltens scale. RESULTS: No differences in WMHs were found between the three groups in the cross-sectional study. A negative correlation was observed between semantic fluency and the subscore for WMHs in the frontal lobe. Of the 36 non-demented patients re-evaluated after a mean follow-up of 30 months, three patients converted into MCI and 5 into dementia. Progression of periventricular WMHs was associated with an increased conversion to dementia. A marginal association between the increase in total WMHs burden and worsening in the Mini Mental State Examination was encountered. CONCLUSIONS: White matter hyperintensities do not influence the cognitive status of patients with PD. Frontal WMHs have a negative impact on semantic fluency. Brain vascular burden may have an effect on cognitive impairment in patients with PD as WMHs increase overtime might increase the risk of conversion to dementia. This finding needs further confirmation in larger prospective studies

Slow oscillatory activity and levodopa-induced dyskinesias in Parkinson’s disease

The pathophysiology of levodopa-induced dyskinesias (LID) in Parkinson’s disease is not well understood. We have recorded local field potentials (LFP) from macroelectrodes implanted in the subthalamic nucleus (STN) of 14 patients with Parkinson’s disease following surgical treatment with deep brain stimulation. Patients were studied in the ‘Off’ medication state and in the ‘On’ motor state after administration of levodopa– carbidopa (po) or apomorphine (sc) that elicited dyskinesias in 11 patients. The logarithm of the power spectrum of the LFP in selected frequency bands (4–10, 11–30 and 60–80 Hz) was compared between the ‘Off’ and ‘On’ medication states. A peak in the 11–30 Hz band was recorded in the ‘Off’ medication state and reduced by 45.2% (P < 0.001) in the ‘On’ state. The ‘On’ was also associated with an increment of 77. 6% (P < 0.001) in the 4–10 Hz band in all patients who showed dyskinesias and of 17.8% (P < 0.001) in the 60–80 Hz band in the majority of patients. When dyskinesias were only present in one limb (n = 2), the 4–10 Hz peak was only recorded in the contralateralSTN. These findings suggest that the 4–10 Hz oscillation is associated with the expression of LID in Parkinson’s disease