Eero Pekkonen

In the quantification of symptoms of Parkinson’s disease (PD), healthcare professional assessments, patient reported outcomes (PRO), and medical device grade wearables are currently used. Recently, also commercially available smartphones and wearable devices have been actively researched in the detection of PD symptoms. The continuous, longitudinal, and automated detection of motor and especially non-motor symptoms with these devices is still a challenge that requires more research. The data collected from everyday life can be noisy and frequently contains artefacts, and novel detection methods and algorithms are therefore needed. 42 PD patients and 23 control subjects were monitored with Garmin Vivosmart 4 wearable device and asked to fill a symptom and medication diary with a mobile application, at home, for about four weeks. Subsequent analyses are based on continuous accelerometer data from the device. Accelerometer data from the Levodopa Response Study (MJFFd) were reanalyzed, with symptoms quantified with linear spectral models trained on expert evaluations present in the data. Variational autoencoders (VAE) were trained on both our study accelerometer data and on MJFFd to detect movement states (e.g., walking, standing). A total of 7590 self-reported symptoms were recorded during the study. 88.9% (32/36) of PD patients, 80.0% (4/5) of DBS PD patients and 95.5% (21/22) of control subjects reported that using the wearable device was very easy or easy. Recording a symptom at the time of the event was assessed as very easy or easy by 70.1% (29/41) of subjects with PD. Aggregated spectrograms of the collected accelerometer data show relative attenuation of low (<5Hz) frequencies in patients. Similar spectral patterns also separate symptom periods from immediately adjacent non-symptomatic periods. Discriminative power of linear models to separate symptoms from adjacent periods is weak, but aggregates show partial separability of patients vs. controls. The analysis reveals differential symptom detectability across movement tasks, motivating the third part of the study. VAEs trained on either dataset produced embedding from which movement states in MJFFd could be predicted. A VAE model was able to detect the movement states. Thus, a pre-detection of these states with a VAE from accelerometer data with good S/N ratio, and subsequent quantification of PD symptoms is a feasible strategy. The usability of the data collection method is important to enable the collection of self-reported symptom data by PD patients. Finally, the usability of the data collection method is important to enable the collection of self-reported symptom data by PD patients.

We describe a 38-year-old male patient with intellectual disability and progressive motor symptoms who lacked an etiological diagnosis for many years. Finally, clinical exome sequencing showed a likely pathogenic variant of the ARX gene suggesting Partington syndrome. His main symptoms were mild intellectual disability, severe kinetic apraxia, resting and action tremor, dysarthria, tonic pupils, constant dystonia of one upper limb, and focal dystonia in different parts of the body, axial rigidity, spasticity, epilepsy, and poor sleep. Another likely pathogenic gene variant was observed in the PKP2 gene and is in accordance with the observed early cardiomyopathy. Single-photon emission computed tomography imaging of dopamine transporters showed a reduced signal in the basal ganglia consistent with Parkinsons disease. Therapies with a variable number of drugs, including antiparkinsonian medications, have yielded poor responses. Our case report extends the picture of the adult phenotype of Partington syndrome.

Gut microbiota alterations in Parkinson’s disease (PD) have been found in several studies and are suggested to contribute to the pathogenesis of PD. However, previous results could not be adequately adjusted for a potential confounding effect of PD medication and disease duration, as almost all PD participants were already using dopaminergic medication and were included several years after diagnosis. Here, the gut microbiome composition of treatment-naive de novo PD subjects was assessed compared to healthy controls (HC) in two large independent case-control cohorts (n = 136 and 56 PD, n = 85 and 87 HC), using 16S-sequencing of fecal samples. Relevant variables such as technical batches, diet and constipation were assessed for their potential effects. Overall gut microbiome composition differed between PD and HC in both cohorts, suggesting gut microbiome alterations are already present in de novo PD subjects at the time of diagnosis, without the possible confounding effect of dopaminergic medication. Although no differentially abundant taxon could be replicated in both cohorts, multiple short chain fatty acids (SCFA) producing taxa were decreased in PD in both cohorts. In particular, several taxa belonging to the family Lachnospiraceae were decreased in abundance. Fewer taxonomic differences were found compared to previous studies, indicating smaller effect sizes in de novo PD.

Directional deep brain stimulation (dDBS) is preferred by patients with advanced Parkinson’s disease (PD) and by programming neurologists. However, real-life data of dDBS use is still scarce. We reviewed the clinical data of 53 PD patients with dDBS to 18 months of follow-up. Directional stimulation was favored in 70.5% of dDBS leads, and single segment activation (SSA) was used in 60% of dDBS leads. Current with SSA was significantly lower than with other stimulation types. During the 6-month follow-up, a 44% improvement in the Unified Parkinson’s Disease Rating Scale (UPDRS-III) points and a 43% decline in the levodopa equivalent daily dosage (LEDD) was observed. After 18 months of follow-up, a 35% LEDD decrease was still noted. The Hoehn and Yahr (H&Y) stages and scores on item no 30 “postural stability” in UPDRS-III remained lower throughout the follow-up compared to baseline. Additionally, dDBS relieved non-motor symptoms during the 6 months of follow-up. Patients with bilateral SSA had similar clinical outcomes to those with other stimulation types. Directional stimulation appears to effectively reduce both motor and non-motor symptoms in advanced PD with minimal adverse effects in real-life clinical care.

Despite optimal oral drug treatment, about 90% of patients with Parkinson's disease develop motor fluctuation and dyskinesia within 5-10 years from the diagnosis. Moreover, the patients show non-motor symptoms in different sensory domains. Bilateral deep brain stimulation (DBS) applied to the subthalamic nucleus is considered the most effective treatment in advanced Parkinson's disease, and it has been suggested to affect sensorimotor modulation and relate to motor improvement in patients. However, observations on the relationship between sensorimotor activity and clinical improvement have remained sparse. Here, we studied the somatosensory evoked magnetic fields in 13 right-handed patients with advanced Parkinson's disease before and 7 months after stimulator implantation. Somatosensory processing was addressed with magnetoencephalography during alternated median nerve stimulation at both wrists. The strengths and the latencies of the similar to 60-ms responses at the contralateral primary somatosensory cortices were highly variable but detectable and reliably localized in all patients. The response strengths did not differ between preoperative and postoperative DBSON measurements. The change in the response strength between preoperative and postoperative condition in the dominant left hemisphere of our right-handed patients correlated with the alleviation of their motor symptoms (p = .04). However, the result did not survive correction for multiple comparisons. Magnetoencephalography appears an effective tool to explore non-motor effects in patients with Parkinson's disease, and it may help in understanding the neurophysiological basis of DBS. However, the high interindividual variability in the somatosensory responses and poor tolerability of DBSOFF condition warrants larger patient groups and measurements also in non-medicated patients.

Objective: Deep brain stimulation (DBS) is an effective treatment for motor symptoms of advanced Parkinson’s disease (PD). Currently, DBS programming outcome is based on a clinical assessment. In an optimal situation, an objectively measurable feature would assist the operator to select the appropriate settings for DBS. Surface electromyographic (EMG) measurements have been used to characterise the motor symptoms of PD with good results; with proper methodology, these measurements could be used as an aid to program DBS. Methods: Muscle activation measurements were performed for 13 patients who had advanced PD and were treated with DBS. The DBS pulse voltage, frequency, and width were changed during the measurements. The measured EMG signals were analysed with parameters that characterise the EMG signal morphology, and the results were compared to the clinical outcome of the adjustment. Results: The EMG signal correlation dimension, recurrence rate, and kurtosis changed significantly when the DBS settings were changed. DBS adjustment affected the signal recurrence rate the most. Relative to the optimal settings, increased recurrence rates (median ± IQR) 1.1 ± 0.5 (−0.3 V), 1.3 ± 1.1 (+0.3 V), 1.7 ± 0.4 (−30 Hz), 1.7 ± 0.8 (+30 Hz), 2.0 ± 1.7 (+30 μs), and 1.5 ± 1.1 (DBS off) were observed. With optimal stimulation settings, the patients’ Unified Parkinson’s Disease Rating Scale motor part (UPDRS-III) score decreased by 35% on average compared to turning the device off. However, the changes in UPRDS-III arm tremor and rigidity scores did not differ significantly in any settings compared to the optimal stimulation settings. Conclusion: Adjustment of DBS treatment alters the muscle activation patterns in PD patients. The changes in the muscle activation patterns can be observed with EMG, and the parameters calculated from the signals differ between optimal and non-optimal settings of DBS. This provides a possibility for using the EMG-based measurement to aid the clinicians to adjust the DBS.

Deep brain stimulation (DBS) has proven its clinical efficacy in Parkinson’s disease (PD), but its exact mechanisms and cortical effects continue to be unclear. Subthalamic (STN) DBS acutely modifies auditory evoked responses, but its long-term effect on auditory cortical processing remains ambiguous. We studied with magnetoencephalography the effect of long-term STN DBS on auditory processing in patients with advanced PD. DBS resulted in significantly increased contra-ipsilateral auditory response latency difference at ~100 ms after stimulus onset compared with preoperative state. The effect is likely due to normalization of neuronal asynchrony in the auditory pathways. The present results indicate that STN DBS in advanced PD patients has long-lasting effects on cortical areas outside those confined to motor processing. Whole-head magnetoencephalography provides a feasible tool to study motor and non-motor neural networks in PD, and to track possible changes related to cortical reorganization or plasticity induced by DBS.

Device-aided therapies, including levodopa-carbidopa intestinal gel infusion, apomorphine subcutaneous infusion, and deep brain stimulation, are available in many countries for the management of the advanced stage of Parkinson’s disease (PD). Currently, selection of device-aided therapies is mainly focused on patients’ motor profile while non-motor symptoms play a role limited to being regarded as possible exclusion criteria in the decision-making process for the delivery and sustenance of a successful treatment. Differential beneficial effects on specific non-motor symptoms of the currently available device-aided therapies for PD are emerging and these could hold relevant clinical implications. In this viewpoint, we suggest that specific non-motor symptoms could be used as an additional anchor to motor symptoms and not merely as exclusion criteria to deliver bespoke and patient-specific personalised therapy for advanced PD.

Dystonia is a movement disorder substantially affecting the quality of life and the ability to work. A proportion of patients does not respond to first line pharmacotherapy. Deep brain stimulation (DBS) is established as a primary operative treatment option for severe drug resistant dystonia. We studied dystonia patients treated with DBS in Finland between the years 2007–2016 to evaluate the use and outcomes of DBS treatment. We analysed the hospital records of dystonia patients, who underwent DBS operation during 2007–2016 in Finland. The clinical and technical parameters were recorded as well as preoperative assessments and treatments. The response to DBS was evaluated retrospectively using the Global Dystonia Rating Scale (GDS). Out of 585 dB implantations during the study period, 37 were done for dystonia. The clinical response improved significantly with time in the isolated focal dystonia group, and at 12 months, 22 of 32 patients had over 50% alleviation of the GDS score. There was only one subclinical intracerebral haemorrhage, and four infections leading to revision. Speech impairment and limb coordination problems were common stimulation- related adverse events and were mostly resolved or relieved with the adjustment of stimulation parameters. DBS seems to be beneficial in dystonia. Although DBS is indicated for dystonia in Finland, the number of operations did not increase at the same rate as DBS operations in general. DBS appears to be a safe and effective treatment for focal as well as generalized dystonia.