Anita Kamondi

Technology in Parkinson's disease: Challenges and opportunities

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinsons disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide‐scale and long‐term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the “big data” acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open‐source and/or open‐hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self‐adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed‐loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico‐pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease‐modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD.

Strategic infarcts of the thalamus in vascular dementia.

Strategic infarcts or focal hemorrhages involving the paramedian nuclei of the thalamus may alter consciousness and produce complex neuropsychological symptoms such as impairment of memory, attention and motivation. Lesions disrupting the thalamo-prefrontal circuits lead to severe subcortical dementia. We analysed here the clinical, neuropsychological and neuroimaging data of 19 patients with cerebrovascular lesions in the thalamus. In six patients with bilateral paramedian infarcts, and in two with anterior thalamic infarcts, vascular dementia and severe personality changes developed. SPECT findings did not correlate with the neuropsychological symptoms. Transcortical sensory and motor aphasia was observed in four patients with thalamic hemorrhages and infarcts. In these patients SPECT detected hypoperfusion in adjacent cortical areas. Clinical symptoms and outcome of four patients are reported in detail. The clinico-morphological correlations of the thalamo-cortical circuits are reviewed and the possible causes of multiple cognitive and behavioural consequences of vascular thalamic lesions are discussed.

Correction of vitamin D deficiency improves seizure control in epilepsy: A pilot study

There is growing interest concerning the role of vitamin D in various medical conditions such as diabetes and oncological, cardiovascular and central nervous system disorders. Although vitamin D deficiency is known to be highly prevalent among epilepsy patients, only a single study, published nearly forty years ago, assessed the effect of vitamin D on seizure control. Here, we measured serum 25-hydroxy-vitamin D (25(OH)D) levels and normalized it by administration of vitamin D3 in 13 patients with pharmacoresistant epilepsy. To see if vitamin D3 has an impact on seizure frequency, we compared seizure numbers during a 90-day period before and after treatment onset. We found that seizure numbers significantly decreased upon vitamin D3 supplementation. Median seizure reduction was 40%. We conclude that the normalization of serum vitamin 25(OH)D level has an anticonvulsant effect.

Impaired rhythm generation in essential tremor

It has been suggested that the cerebellum plays a role in the event‐based timing of synchronized repetitive movements. We hypothesized that regularity of rhythmic movements in essential tremor (ET) is impaired, since several lines of evidence suggest the involvement of the cerebellum in the pathomechanism of ET. To test this assumption, we examined the regularity and the maximum frequency of auditory paced repetitive movements at slow and fast stimulus rate in 34 ET patients. Variability of rhythmic finger tapping and alternating hand movements, defined by the standard deviation of movement offset before or after the pacing signal, was significantly higher compared to healthy controls. Timing of rhythmic movements of the two hands was disturbed to the same degree. Our results suggest a severe deficit of event‐based rhythm generation on both sides in ET, supporting the presumed bilateral cerebellar dysfunction in this disorder.

Epileptic Seizures in Alzheimer Disease: A Review.

Alzheimer disease (AD) is the most frequent cause of major neurocognitive disorders with a huge economical and medical burden. Several studies pointed out that AD is associated with a high risk for developing epileptic seizures. The aims of our review were to evaluate and to summarize the current literature (ending in September 2015) of animal and human studies in the relation of AD and epileptic seizures. It seems likely that epileptic hyperexcitation could be partially responsible for the progression of AD due to the increased rate of amyloid deposition. Pathologic changes in animal models of AD are similar to those seen in human temporal lobe epilepsy. Antiepileptic treatment had a positive effect on cognitive function in animal and human studies. Because the detection of seizures in patients with cognitive decline is extremely difficult because of methodological problems, the true prevalence of seizures has remained unclear. Nonconvulsive seizures with no overt clinical symptoms may be frequent seizure types in AD. These are difficult to detect by clinical observation and with standard scalp electroencephalogram (EEG) methods. We propose that long-term EEG recording and video-EEG monitoring is necessary to prove the presence of epileptiform activity in demented patients.

Impairment of post-movement beta synchronisation in parkinson's disease is related to laterality of tremor

OBJECTIVE Post-movement beta synchronisation (PMBS) is a physiological indicator of the activity of movement related neural networks. To investigate the pathophysiology of this phenomenon, we examined its characteristics in patients with unilateral tremor-dominant Parkinsons disease (PD). METHODS Movement duration and PMBS was measured after self-paced movement of the thumb at movement-reactive beta frequencies, over the supplementary motor area in 10 PD patients and 8 control subjects. RESULTS Movement duration in PD patients was longer than in controls. In left hand tremor patients, movement of the left hand was significantly longer compared to the right hand. When PD patients moved their non-affected hand, similarly to the controls, PMBS was higher contralateral to the movement. After movement of the tremulous hand, the contralateral PMBS decreased significantly and the contralateral preponderance disappeared. In the same hemisphere, PMBS was higher after contralateral to the non-affected hand movement, than after ipsilateral to the tremulous hand after movement. CONCLUSIONS PMBS in PD is affected by the activity of tremor related neural networks, suggesting that both cortical and subcortical sources are responsible for its generation. Examination of PMBS in various neurological diseases might provide further data on its physiological significance.

Is the MDS-UPDRS a Good Screening Tool for Detecting Sleep Problems and Daytime Sleepiness in Parkinson’s Disease?

Movement Disorder Society-sponsored Unified Parkinsons Disease Rating Scale (MDS-UPDRS) has separate items for measuring sleep problems (item 1.7) and daytime sleepiness (1.8). The aim of our study was to evaluate the screening sensitivity and specificity of these items to the PD Sleep Scale 2nd version (PDSS-2) and Epworth Sleepiness Scale (ESS). In this nationwide, cross-sectional study 460 PD patients were enrolled. Spearmans rank correlation coefficients were calculated between the individual items, domains, and the total score of PDSS-2 and item 1.7 of MDS-UPDRS. Similarly, the items and the total score of ESS were contrasted to item 1.8 of MDS-UPDRS. After developing generalized ordinal logistic regression models, the transformed and observed scores were compared by Lins Concordance Correlation Coefficient. Only item 3 difficulties staying asleep and the “disturbed sleep” domain of PDSS-2 showed high correlation with “sleep problems” item 1.7 of the MDS-UPDRS. Total score of PDSS-2 had moderate correlation with this MDS-UPRDS item. The total score of ESS showed the strongest, but still moderate, correlation with “daytime sleepiness” item 1.8 of MDS-UPDRS. As intended, the MDS-UPDRS serves as an effective screening tool for both sleep problems and daytime sleepiness and identifies subjects whose disabilities need further investigation.

Delayed beta synchronization after movement of the more affected hand in essential tremor.

To investigate the pathomechanism of parkinsonian tremor (PT) and essential tremor (ET) by studying the correlation between tremor asymmetry and post-movement beta synchronization (PMBS) of the human EEG. We recorded the EEG of 10 patients with ET, 10 patients with Parkinsons disease and 10 controls. Subjects pressed an on-off switch in a self-paced manner with the thumb of their less (T+) and more (T++) tremulous hand. After digitalization of the EEG from the Cz, C3, C4 electrodes the movement reactive beta frequency, its maximum peak power value and its latency triggered to movement offset were determined. In ET tremor intensity did not influence the power of PMBS, however it was significantly delayed after the movement of the more tremulous hand. In Parkinsons disease after the movement of the more tremulous hand PMBS power was decreased, but it was not delayed. In controls the side of movement had no effect on the power and latency of the PMBS. The neuronal mechanisms underlying PMBS generation are differently affected in essential tremor and Parkinsons disease. The increase of PMBS latency after movement of the more affected hand in ET indicates possible cortical mechanisms in essential tremor generation.

Leukoencephalopathy, cerebral calcifications and cysts: A family study

We present a clinical, neuro-radiological and genetic study on a family with members suffering from an autosomal dominantly inherited syndrome characterised by epilepsy, cerebral calcifications and cysts, bone abnormalities; progressive neuro-cognitive deterioration and paranasal sinusitis. This syndrome shares several features with leukoencephalopathy with calcifications and cysts also called Labrune syndrome and the condition of cerebroretinal microangiopathy with calcifications and cysts (CRMCC; Coats plus syndrome). Genetic studies in this family did not reveal mutations in the CTC1 gene defected in CRMCC. We interpret our results as those supporting recent findings that despite clinical similarities, late-onset Labrune and Coats plus syndrome might be distinct entities. This family may have Labrune syndrome or a yet unclassified entity; exploration of similar cases could help classifying this one, and related conditions.

Contralateral voluntary hand movement inhibits human parkinsonian tremor and variably influences essential tremor

While voluntary movement blocks Parkinsonian rest tremor (PT), essential tremor (ET) is enforced by postural and/or kinetic action. We studied the effect of contralateral externally- and internally triggered hand movement on PT and ET to investigate the transhemispheric influences on tremor genesis. We measured the changes of tremor peak frequency power after flash signal (F), flash triggered (FM) and self-paced (SPM) movement of the contralateral hand in nine PT and seven ET patients using accelerometer. PT significantly decreased both during FM and SPM tasks, suggesting that it is generated by a constant subcortico-cortical network, which includes higher order motor areas. Intensity of ET showed a remarkable intra- and interindividual variability both during FM and SPM reflecting a different generator circuitry with variable functional connections.