Franco Valzania

Feature Selection for Accelerometer-Based Posture Analysis in Parkinson's Disease

Posture analysis in quiet standing is a key component of the clinical evaluation of Parkinsons disease (PD), postural instability being one of PDs major symptoms. The aim of this study was to assess the feasibility of using accelerometers to characterize the postural behavior of early mild PD subjects. Twenty PD and 20 control subjects, wearing an accelerometer on the lower back, were tested in five conditions characterized by sensory and attentional perturbation. A total of 175 measures were computed from the signals to quantify tremor, acceleration, and displacement of body sway. Feature selection was implemented to identify the subsets of measures that better characterize the distinctive behavior of PD and control subjects. It was based on different classifiers and on a nested cross validation, to maximize robustness of selection with respect to changes in the training set. Several subsets of three features achieved misclassification rates as low as 5%. Many of them included a tremor-related measure, a postural measure in the frequency domain, and a postural displacement measure. Results suggest that quantitative posture analysis using a single accelerometer and a simple test protocol may provide useful information to characterize early PD subjects. This protocol is potentially usable to monitor the diseases progression.

Quantification of Motor Impairment in Parkinson's Disease Using an Instrumented Timed Up and Go Test

The Timed Up and Go (TUG) test is a clinical test to assess mobility in Parkinsons disease (PD). It consists of rising from a chair, walking, turning, and sitting. Its total duration is the traditional clinical outcome. In this study an instrumented TUG (iTUG) was used to supplement the quantitative information about the TUG performance of PD subjects: a single accelerometer, worn at the lower back, was used to record the acceleration signals during the test and acceleration-derived measures were extracted from the recorded signals. The aim was to select reliable measures to identify and quantify the differences between the motor patterns of healthy and PD subjects; in order to do so, besides comparing each measure individually to find significant group differences, feature selection and classification were used to identify the distinctive motor pattern of PD subjects. A subset of three features (two from Turning, one from the Sit-to-Walk component), combined with an easily-interpretable classifier (Linear Discriminant Analysis), was found to have the best accuracy in discriminating between healthy and early-mild PD subjects. These results suggest that the proposed iTUG can characterize PD motor impairment and, hence, may be used for evaluation, and, prospectively, follow-up, and monitoring of disease progression.

Dopamine-Agonists and Impulsivity in Parkinson's Disease: Impulsive Choices vs. Impulsive Actions

The control of impulse behavior is a multidimensional concept subdivided into separate subcomponents, which are thought to represent different underlying mechanisms due to either disinhibitory processes or poor decision‐making. In patients with Parkinsons disease (PD), dopamine‐agonist (DA) therapy has been associated with increased impulsive behavior. However, the relationship among these different components in the disease and the role of DA is not well understood. In this imaging study, we investigated in PD patients the effects of DA medication on patterns of brain activation during tasks testing impulsive choices and actions. Following overnight withdrawal of antiparkinsonian medication, PD patients were studied with a H2 (15)O PET before and after administration of DA (1 mg of pramipexole), while they were performing the delay discounting task (DDT) and the GoNoGo Task (GNG). We observed that pramipexole augmented impulsivity during DDT, depending on reward magnitude and activated the medial prefrontal cortex and posterior cingulate cortex and deactivated ventral striatum. In contrast, the effect of pramipexole during the GNG task was not significant on behavioral performance and involved different areas (i.e., lateral prefrontal cortex). A voxel‐based correlation analysis revealed a significant negative correlation between the discounting value (k) and the activation of medial prefrontal cortex and posterior cingulate suggesting that more impulsive patients had less activation in those cortical areas. Here we report how these different subcomponents of inhibition/impulsivity are differentially sensitive to DA treatment with pramipexole influencing mainly the neural network underlying impulsive choices but not impulsive action. Hum Brain Mapp 35:2499–2506, 2014.

MRI Correlates of Parkinson’s Disease Progression: A Voxel Based Morphometry Study

We investigated structural brain differences between a group of early-mild PD patients at different phases of the disease and healthy subjects using voxel-based morphometry (VBM). 20 mild PD patients compared to 15 healthy at baseline and after 2 years of follow-up. VBM is a fully automated technique, which allows the identification of regional differences in the gray matter enabling an objective analysis of the whole brain between groups of subjects. With respect to controls, PD patients exhibited decreased GM volumes in right putamen and right parietal cortex. After 2 years of disease, the same patients confirmed GM loss in the putamen and parietal cortex; a significant difference was also observed in the area of pedunculopontine nucleus (PPN) and in the mesencephalic locomotor region (MLR). PD is associated with brain morphological changes in cortical and subcortical structures. The first regions to be affected in PD seem to be the parietal cortex and the putamen. A third structure that undergoes atrophy is the part of the inferior-posterior midbrain, attributable to the PPN and MLR. Our findings provide new insight into the brain involvement in PD and could contribute to a better understanding of the sequence of events occurring in these patients.

Mortality, morbidity and refractoriness prediction in status epilepticus: Comparison of STESS and EMSE scores

PURPOSE Status epilepticus (SE) is a neurological emergency, characterized by high short-term morbidity and mortality. We evaluated and compared two scores that have been developed to evaluate status epilepticus prognosis: STESS (Status Epilepticus Severity Score) and EMSE (Epidemiology based Mortality score in Status Epilepticus). METHODS A prospective observational study was performed on consecutive patients with SE admitted between September 2013 and August 2015. Demographics, clinical variables, STESS-3 and -4, and EMSE-64 scores were calculated for each patient at baseline. SE drug response, 30-day mortality and morbidity were the outcomes measure. RESULTS 162 episodes of SE were observed: 69% had a STESS ≥3; 34% had a STESS ≥4; 51% patients had an EMSE ≥64. The 30-days mortality was 31.5%: EMSE-64 showed greater negative predictive value (NPV) (97.5%), positive predictive value (PPV) (59.8%) and accuracy in the prediction of death than STESS-3 and STESS-4 (p<0.001). At 30 days, the clinical condition had deteriorated in 59% of the cases: EMSE-64 showed greater NPV (71.3%), PPV (87.8%) and accuracy than STESS-3 and STESS-4 (p<0.001) in the prediction of this outcome. In 23% of all cases, status epilepticus proved refractory to non-anaesthetic treatment. All three scales showed a high NPV (EMSE-64: 87.3%; STESS-4: 89.4%; STESS-3: 87.5%) but a low PPV (EMSE-64: 40.9%; STESS-4: 52.9%; STESS-3: 32%) for the prediction of refractoriness to first and second line drugs. This means that accuracy for the prediction of refractoriness was equally poor for all scales. CONCLUSIONS EMSE-64 appears superior to STESS-3 and STESS-4 in the prediction of 30-days mortality and morbidity. All scales showed poor accuracy in the prediction of response to first and second line antiepileptic drugs. At present, there are no reliable scores capable of predicting treatment responsiveness.

Subthalamic nucleus stimulation in Parkinson’s disease

Deep brain stimulation (DBS) is an effective surgical treatment for advanced Parkinson’s disease (PD), with significant advantages in morbidity-mortality and quality of life when compared to lesion techniques such as thalamotomy and/or pallidotomy. The procedure is indicated in patients with severe resting tremor, unresponsive to conventional medical treatment or with motor complications. The most commonly reported complications in the intra- and post-surgical period are aborted procedure, misplaced leads, intracranial haemorrhage, seizures and hardware complications, whereas in the long-term period, cognitive and psychiatric complications can be observed. The most important eligibility criteria for DBS are: a correct diagnosis of idiopathic PD, severity of illness, a consistent levodopa response and absence of cognitive impairment. Chronological age and mood disorders may be relative contraindications to be individually evaluated. Tremor, rigidity dystonias and dyskinesias improve dramatically after DBS; freezing, postural instability and falls remain unchanged, whereas verbal fluency and dysarthria are known to worsen.

Classification of Early-Mild Subjects with Parkinson’s Disease by Using Sensor-Based Measures of Posture, Gait, and Transitions

Evaluation of posture, gait, turning, and different kind of transitions, are key components of the clinical evaluation of Parkinson’s disease (PD). The aim of this study is to assess the feasibility of using accelerometers to classify early PD subjects (two evaluations over a 1-year follow-up) with respect to age-matched control subjects. Classifying PD subjects in an early stage would permit to obtain a tool able to follow the progression of the disease from the early phases till the last ones and to evaluate the efficacy of different treatments. Two functional tests were instrumented by a single accelerometer (quiet standing, Timed Up and Go test); such tests carry quantitative information about impairments in posture, gait, and transitions (i.e. Sit-to-Walk, and Walk-to-Sit, Turning). Satisfactory accuracies are obtained in the classification of PD subjects by using an ad hoc wrapper feature selection technique.

Long-term disability and prognostic factors in polyneuropathy associated with anti-myelin-associated glycoprotein (MAG) antibodies

Aim of the study: Neuropathy associated with IgM monoclonal gammopathy (MGUS) represents distinctive clinical syndrome, characterized by male predominance, late age of onset, slow progression, predominantly sensory symptoms, deep sensory loss, ataxia, minor motor impairment. More than 50% of patients with neuropathy-associated MGUS possess antibodies against myelin-associated glycoprotein (MAG). Purpose of our study was to assess effects on disease progression of demographic, clinical and neurophysiological variables in our large cohort of patients. Materials and Methods: Forty-three Caucasians patients were followed every eight months for median duration time of 93 months. Extremity strength was assessed with Medical Research Council (MRC) Scale, disability with overall disability status scale (ODSS), modified Rankin Scale and sensory function with Inflammatory Neuropathy Cause and Treatment (INCAT) sensory scale (ISS). Statistical analyses were conducted with parametric or non-parametric measures as appropriate. Survival analysis was used to test predictive value of clinical, demographical and neurophysiological variables. Variance analysis was conducted to explain difference on MRC between patients and groups at different time from onset. Results: Results showed that demyelinating pattern, older age and absence of treatment were significant risk factors for disability worsening. No other factors emerged as predictors including gender, ataxia and tremor at baseline, level of anti-MAG and IgM protein concentration in serum. Despite worsening of all outcome measures between first and last visit, quality of life (HRQol) judged by patients did not vary significantly. Conclusions: Our study provides evidence that electrophysiologic pattern, age of onset and absence of treatment are strong predictor of prognosis in anti-MAG polyneuropathy.

Preliminary results of ON/OFF detection using an integrated system for Parkinson's disease monitoring

This paper describes the experimental set up of a system composed by a set of wearable sensors devices for the recording of the motion signals and software algorithms for the signal analysis. This system is able to automatically detect and assess the severity of bradykinesia, tremor, dyskinesia and akinesia motor symptoms. Based on the assessment of the akinesia, the ON-OFF status of the patient is determined for each moment. The assessment performed through the automatic evaluation of the akinesia is compared with the status reported by the patients in their diaries. Preliminary results with a total recording period of 32 hours with two PD patients are presented, where a good correspondence (88.2 +/- 3.7 %) was observed. Best (93.7%) and worst (87%) correlation results are illustrated, together with the analysis of the automatic assessment of the akinesia symptom leading to the status determination. The results obtained are promising, and if confirmed with further data, this automatic assessment of PD motor symptoms will lead to a better adjustment of medication dosages and timing, cost savings and an improved quality of life of the patients.

Cranial nerve involvement as presenting sign of multifocal motor neuropathy

Multifocal motor neuropathy (MMN) is characterized by slowly progressive, predominantly distal, asymmetric limb weakness and partial conduction blocks (CB) of motor axons. Cranial nerve involvement and respiratory failure are uncommon. We report two patients who exhibited unilateral hypoglossal and abducens palsy as presenting signs. Other remarkable features were autonomic instability and respiratory failure due to bilateral phrenic nerve involvement. Treatment with intravenous (IV) immunoglobulin (Ig) resulted in an improvement. Patient 2, who showed IgM reactivity against ganglioside GM1, has been receiving maintenance therapy with IVIg for 7 years. We speculate that cranial weakness of our patients could be due to CB similar to those detected in the motor nerves of the extremities.