Among Parkinson's disease (PD) symptoms, freezing of gait (FoG) is one of the most debilitating. To assess FoG, current clinical practice mostly employs repeated evaluations over weeks and months ...based on questionnaires, which may not accurately map the severity of this symptom. The use of a non-invasive system to monitor the activities of daily living (ADL) and the PD symptoms experienced by patients throughout the day could provide a more accurate and objective evaluation of FoG in order to better understand the evolution of the disease and allow for a more informed decision-making process in making adjustments to the patient's treatment plan. This paper presents a new algorithm to detect FoG with a machine learning approach based on Support Vector Machines (SVM) and a single tri-axial accelerometer worn at the waist. The method is evaluated through the acceleration signals in an outpatient setting gathered from 21 PD patients at their home and evaluated under two different conditions: first, a generic model is tested by using a leave-one-out approach and, second, a personalised model that also uses part of the dataset from each patient. Results show a significant improvement in the accuracy of the personalised model compared to the generic model, showing enhancement in the specificity and sensitivity geometric mean (GM) of 7.2%. Furthermore, the SVM approach adopted has been compared to the most comprehensive FoG detection method currently in use (referred to as MBFA in this paper). Results of our novel generic method provide an enhancement of 11.2% in the GM compared to the MBFA generic model and, in the case of the personalised model, a 10% of improvement with respect to the MBFA personalised model. Thus, our results show that a machine learning approach can be used to monitor FoG during the daily life of PD patients and, furthermore, personalised models for FoG detection can be used to improve monitoring accuracy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Among Parkinson’s disease (PD) motor symptoms, freezing of gait (FOG) may be the most incapacitating. FOG episodes may result in falls and reduce patients’ quality of life. Accurate assessment of FOG ...would provide objective information to neurologists about the patient’s condition and the symptom’s characteristics, while it could enable non-pharmacologic support based on rhythmic cues.
This paper is, to the best of our knowledge, the first study to propose a deep learning method for detecting FOG episodes in PD patients. This model is trained using a novel spectral data representation strategy which considers information from both the previous and current signal windows. Our approach was evaluated using data collected by a waist-placed inertial measurement unit from 21 PD patients who manifested FOG episodes. These data were also employed to reproduce the state-of-the-art methodologies, which served to perform a comparative study to our FOG monitoring system.
The results of this study demonstrate that our approach successfully outperforms the state-of-the-art methods for automatic FOG detection. Precisely, the deep learning model achieved 90% for the geometric mean between sensitivity and specificity, whereas the state-of-the-art methods were unable to surpass the 83% for the same metric.
Topoisomerase II (TOP2) removes torsional stress from DNA and facilitates gene transcription by introducing transient DNA double-strand breaks (DSBs). Such DSBs are normally rejoined by TOP2 but on ...occasion can become abortive and remain unsealed. Here we identify homozygous mutations in the TDP2 gene encoding tyrosyl DNA phosphodiesterase-2, an enzyme that repairs 'abortive' TOP2-induced DSBs, in individuals with intellectual disability, seizures and ataxia. We show that cells from affected individuals are hypersensitive to TOP2-induced DSBs and that loss of TDP2 inhibits TOP2-dependent gene transcription in cultured human cells and in mouse post-mitotic neurons following abortive TOP2 activity. Notably, TDP2 is also required for normal levels of many gene transcripts in developing mouse brain, including numerous gene transcripts associated with neurological function and/or disease, and for normal interneuron density in mouse cerebellum. Collectively, these data implicate chromosome breakage by TOP2 as an endogenous threat to gene transcription and to normal neuronal development and maintenance.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
This review will discuss the expanding clinical spectrum of paroxysmal movement disorders and therapeutic options in light of emerging genotypic heterogeneity in these conditions.
Paroxysmal movement ...disorders comprise a heterogeneous group of rare neurological conditions characterized by intermittent episodes of abnormal movement associated with various triggers. As the clinical and genotypic spectrum of these disorders evolves, so also has the range of therapeutic options. Triheptanoin has recently been shown to be a very promising alternative to the ketogenic diet in paroxysmal exercise-induced dyskinesia. Four-aminopyridine is now considered first-line symptomatic therapy for episodic ataxia type-2, with pre-clinical findings indicating cerebellar neuroprotection.
In light of the newly emerging therapies, careful clinical phenotyping is needed to ensure diagnostic precision and timely initiation of appropriate therapies.
Parkin Disease: A Clinicopathologic Entity? Doherty, Karen M; Silveira-Moriyama, Laura; Parkkinen, Laura ...
JAMA neurology,
05/2013, Letnik:
70, Številka:
5
Journal Article
Recenzirano
Odprti dostop
IMPORTANCE Mutations in the gene encoding parkin (PARK2) are the most common cause of autosomal recessive juvenile-onset and young-onset parkinsonism. The few available detailed neuropathologic ...reports suggest that homozygous and compound heterozygous parkin mutations are characterized by severe substantia nigra pars compacta neuronal loss. OBJECTIVE To investigate whether parkin -linked parkinsonism is a different clinicopathologic entity to Parkinson disease (PD). DESIGN, SETTING, AND PARTICIPANTS We describe the clinical, genetic, and neuropathologic findings of 5 unrelated cases of parkin disease and compare them with 5 pathologically confirmed PD cases and 4 control subjects. The PD control cases and normal control subjects were matched first for age at death then disease duration (PD only) for comparison. RESULTS Presenting signs in the parkin disease cases were hand or leg tremor often combined with dystonia. Mean age at onset was 34 years; all cases were compound heterozygous for mutations of parkin. Freezing of gait, postural deformity, and motor fluctuations were common late features. No patients had any evidence of cognitive impairment or dementia. Neuronal counts in the substantia nigra pars compacta revealed that neuronal loss in the parkin cases was as severe as that seen in PD, but relative preservation of the dorsal tier was seen in comparison with PD (P = .04). Mild neuronal loss was identified in the locus coeruleus and dorsal motor nucleus of the vagus, but not in the nucleus basalis of Meynert, raphe nucleus, or other brain regions. Sparse Lewy bodies were identified in 2 cases (brainstem and cortex). CONCLUSIONS AND RELEVANCE These findings support the notion that parkin disease is characterized by a more restricted morphologic abnormality than is found in PD, with predominantly ventral nigral degeneration and absent or rare Lewy bodies.
Cognitive difficulties experienced by people with multiple sclerosis (MS) impact on quality of life and daily functioning, from childcare and work to social and self-care activities. The Cognitive ...Occupation-Based programme for people with MS (COB-MS) was developed as a holistic, individualised cognitive rehabilitation intervention to address the wide-ranging symptoms and functional difficulties that present in MS, including the ability to maintain employment, social activities, home management and self-care. The aim of the research is to evaluate the feasibility and preliminary efficacy of COB-MS for people with MS.
Due to the impacts of COVID-19, trial activities that were planned for in-person delivery were completed remotely. One hundred and twenty people with MS will be assigned to participate in either the COB-MS programme or a treatment-as-usual, wait-list control group as part of this single-blind, cluster-randomised controlled feasibility and preliminary efficacy trial of the COB-MS programme. The COB-MS group will participate in an eight-session occupational-based cognitive rehabilitation programme over 9 weeks. The COB-MS intervention was planned for in-person delivery but was delivered online by occupational therapists to small groups of people with MS. The primary outcome measure is the Goal Attainment Scaling at 12 weeks. Participants will be assessed pre-intervention, post-intervention, 12 weeks post-intervention and 6 months post-intervention. Qualitative evaluations of participants' perspectives will also be examined as part of the feasibility study. Data, due to be collected in-person, was collected online or by post. The original study design, including the statistical analysis plan, remains unchanged despite the shift to a remote trial conduct.
Results will provide recommendations for a future definitive trial of COB-MS, with respect to both feasibility and preliminary, clinical efficacy.
ISRCTN ISRCTN11462710 . Registered on 9 September 2019 and updated on 23 September 2020 to account for changes outlined here.
A 74-year-old farmer presented to the emergency department with a subacute history of progressive dyspnoea, wheeze and dysphonia. He was treated for an exacerbation of asthma with poor response to ...pharmacological therapy. Investigation of dysphonia via laryngoscopy identified a bilateral vocal cord palsy. Subsequently, the patient developed an episode of life-threatening stridor and hypercapnic respiratory failure requiring an emergency tracheostomy. Neurology input identified evidence of widespread muscle fasciculations on clinical examination. MRI of the brain and cervical spine were unremarkable. Electromyogram testing identified changes of acute denervation in several limbs consistent with a diagnosis of motor neuron disease (MND). Bilateral vocal cord palsy has been rarely reported in the literature as the heralding symptom resulting in the diagnosis of MND. In patients with a subacute onset of dysphonia, dyspnoea and stridor, MND should be a differential diagnosis.
Several factors are thought to contribute to inadequate seizure control in patients with juvenile myoclonic epilepsy (JME), including drug resistance, neuropsychiatric comorbidity, and poor lifestyle ...choices. Recent evidence supports the existence of frontal lobe microstructural deficits and behavioral changes that may contribute to poor seizure control in a minority of patients. Counseling patients on the importance of adequate sleep hygiene and alcohol restriction is an important part of the management strategy for patients with JME. However, information is lacking on how these lifestyle restrictions impact on patients with JME. We conducted a qualitative descriptive analysis of the social impact of JME on 12 patients, from their own perspective. We identified four prominent themes: the importance of alcohol use as a social “norm”, how JME affected relationships, decision making (risk versus consequences), and knowledge imparting control. Given that these restrictions were interpreted by patients as social “curfews”, we suggest that the term “Cinderella Syndrome” encapsulates the perceived imperative to be home before midnight. Our findings underscore the importance for clinicians to recognize that in counseling patients with JME about lifestyle adjustments, there may be a significant social consequence unique to this patient group.
•The social consequences of lifestyle restrictions in patients with JME are presented.•Alcohol and sleep constraints impact social function in patients with JME.•The term “Cinderella Syndrome” is proposed to highlight social curfews in JME.
PDF
