COVID19-associated new-onset movement disorders: a follow-up study.

BACKGROUND: Neurological symptoms are common manifestation in acute COVID-19. This includes hyper- and hypokinetic movement disorders. Data on their outcome, however, is limited. METHODS: Cases with new-onset COVID-19-associated movement disorders were identified by searching the literature. Authors were contacted for outcome data which were reviewed and analyzed. RESULTS: Movement disorders began 12.6 days on average after the initial onset of COVID-19. 92% of patients required hospital admission (mean duration 23 days). In a fraction of patients (6 of 27; 22%; 4 males/2 females, mean age 66.8 years) the movement disorder (ataxia, myoclonus, tremor, parkinsonism) was still present after a follow-up period of 7.5 ± 3 weeks. Severe COVID-19 in general and development of encephalopathy were risk factors, albeit not strong predictors, for the persistence. CONCLUSIONS: The prognosis of new-onset COVID-19-associated movement disorder appears to be generally good. The majority recovered without residual symptoms within several weeks or months. Permanent cases may be due to unmasking of a previous subclinical movement disorder or due to vascular/demyelinating damage. Given the relatively low response rate of one third only and the heterogeneity of mechanisms firm conclusions on the (long-term) outome cannot, however, be drawn.

Classification of Kinematic and Electromyographic Signals Associated with Pathological Tremor Using Machine and Deep Learning.

Peripheral Electrical Stimulation (PES) of afferent pathways has received increased interest as a solution to reduce pathological tremors with minimal side effects. Closed-loop PES systems might present some advantages in reducing tremors, but further developments are required in order to reliably detect pathological tremors to accurately enable the stimulation only if a tremor is present. This study explores different machine learning (K-Nearest Neighbors, Random Forest and Support Vector Machines) and deep learning (Long Short-Term Memory neural networks) models in order to provide a binary (Tremor; No Tremor) classification of kinematic (angle displacement) and electromyography (EMG) signals recorded from patients diagnosed with essential tremors and healthy subjects. Three types of signal sequences without any feature extraction were used as inputs for the classifiers: kinematics (wrist flexion-extension angle), raw EMG and EMG envelopes from wrist flexor and extensor muscles. All the models showed high classification scores (Tremor vs. No Tremor) for the different input data modalities, ranging from 0.8 to 0.99 for the f1 score. The LSTM models achieved 0.98 f1 scores for the classification of raw EMG signals, showing high potential to detect tremors without any processed features or preliminary information. These models may be explored in real-time closed-loop PES strategies to detect tremors and enable stimulation with minimal signal processing steps.

Prediction of Pathological Tremor Signals Using Long Short-Term Memory Neural Networks.

Previous implementations of closed-loop peripheral electrical stimulation (PES) strategies have provided evidence about the effect of the stimulation timing on tremor reduction. However, these strategies have used traditional signal processing techniques that only consider phase prediction and might not model the non-stationary behavior of tremor. Here, we tested the use of long short-term memory (LSTM) neural networks to predict tremor signals using kinematic data recorded from Essential Tremor (ET) patients. A dataset comprising wrist flexion-extension data from 12 ET patients was pre-processed to feed the predictors. A total of 180 models resulting from the combination of network (neurons and layers of the LSTM networks, length of the input sequence and prediction horizon) and training parameters (learning rate) were trained, validated and tested. Predicted tremor signals using LSTM-based models presented high correlation values (from 0.709 to 0.998) with the expected values, with a phase delay between the predicted and real signals below 15 ms, which corresponds approximately to 7.5% of a tremor cycle. The prediction horizon was the parameter with a higher impact on the prediction performance. The proposed LSTM-based models were capable of predicting both phase and amplitude of tremor signals outperforming results from previous studies (32--56% decreased phase prediction error compared to the out-of-phase method), which might provide a more robust PES-based closed-loop control applied to PES-based tremor reduction.

Seizures and COVID-19: Results from the Spanish Society of Neurology's COVID-19 registry.

We describea series of patients with COVID-19 who presented with seizures, reported in the Spanish Society of Neurology's COVID-19 Registry. This observational, descriptive,multicentre, registry-based study includes patients with confirmed COVID-19 who experienced seizures during active infection.Wedescribe theclinicalpresentation of COVID-19,seizures,and resultsof complementary tests.Wealsodescribe the suspectedaetiologyof the seizures. Of 232 reported cases, 26 (11.2%) presented with seizures;7 of these patients (26.9%) had prior history of epilepsy, whereas the remaining 19 (73.1%) had no history of seizures.In most cases, seizures presented on days 0 and 7 after onset of COVID-19. By seizure type, 8 patients (30.7%) presentedgeneralised tonic-clonic seizures, 7 (26.9%) status epilepticus, 8 (30.7%) focal impaired-awareness seizures, and 4 (11.7%) secondary generalised seizures.Six patients (23.1%) also presented other neurological symptoms, includingaltered mental status and decreased level of consciousness. Predisposing factors for seizures (eg, dementia, tumour, cerebrovascular disease) were observed in 10 of the 19 patients with no prior history of epilepsy (52.6%). Patients with COVID-19 may present with seizures over the course of the disease,either alone or in the context of encephalopathy.Seizures may present in patients with no prior history of epilepsy; however, most of these patients present predisposing factors.

Neurological complications of COVID-19 in hospitalized patients: The registry of a neurology department in the first wave of the pandemic.

OBJECTIVE: To describe the spectrum of neurological complications observed in a hospital-based cohort of COVID-19 patients who required a neurological assessment. METHODS: We conducted an observational, monocentric, prospective study of patients with a COVID-19 diagnosis hospitalized during the 3-month period of the first wave of the COVID-19 pandemic in a tertiary hospital in Madrid (Spain). We describe the neurological diagnoses that arose after the onset of COVID-19 symptoms. These diagnoses could be divided into different groups. RESULTS: Only 71 (2.6%) of 2750 hospitalized patients suffered at least one neurological complication (77 different neurological diagnoses in total) during the timeframe of the study. The most common diagnoses were neuromuscular disorders (33.7%), cerebrovascular diseases (CVDs) (27.3%), acute encephalopathy (19.4%), seizures (7.8%), and miscellanea (11.6%) comprising hiccups, myoclonic tremor, Horner syndrome and transverse myelitis. CVDs and encephalopathy were common in the early phase of the COVID-19 pandemic compared to neuromuscular disorders, which usually appeared later on (p = 0.005). Cerebrospinal fluid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction was negative in 15/15 samples. The mortality was higher in the CVD group (38.1% vs. 8.9%; p = 0.05). CONCLUSIONS: The prevalence of neurological complications is low in patients hospitalized for COVID-19. Different mechanisms appear to be involved in these complications, and there was no evidence of direct invasion of the nervous system in our cohort. Some of the neurological complications can be classified into early and late neurological complications of COVID-19, as they occurred at different times following the onset of COVID-19 symptoms.

Intramuscular Stimulation of Muscle Afferents Attains Prolonged Tremor Reduction in Essential Tremor Patients.

This study proposes and clinically tests intramuscular electrical stimulation below motor threshold to achieve prolonged reduction of wrist flexion/extension tremor in Essential Tremor (ET) patients. The developed system consisted of an intramuscular thin-film electrode structure that included both stimulation and electromyography (EMG) recording electrodes, and a control algorithm for the timing of intramuscular stimulation based on EMG (closed-loop stimulation). Data were recorded from nine ET patients with wrist flexion/extension tremor recruited from the Gregorio Marañón Hospital (Madrid, Spain). Patients participated in two experimental sessions comprising: 1) sensory stimulation of wrist flexors/extensors via thin-film multichannel intramuscular electrodes; and 2) surface stimulation of the nerves innervating the same target muscles. For each session, four of these patients underwent random 60-s trials of two stimulation strategies for each target muscle: 1) selective and adaptive timely stimulation (SATS) - based on EMG of the antagonist muscle; and 2) continuous stimulation (CON) of target muscles. Two patients underwent SATS stimulation trials alone while the other three underwent CON stimulation trials alone in each session. Kinematics of wrist, elbow, and shoulder, together with clinical scales, were used to assess tremor before, right after, and 24 h after each session. Intramuscular SATS achieved, on average, 32% acute (during stimulation) tremor reduction on each trial, while continuous stimulation augmented tremorgenic activity. Furthermore, tremor reduction was significantly higher using intramuscular than surface stimulation. Prolonged reduction of tremor amplitude (24 h after the experiment) was observed in four patients. These results showed acute and prolonged (24 h) tremor reduction using a minimally invasive neurostimulation technology based on SATS of primary sensory afferents of wrist muscles. This strategy might open the possibility of an alternative therapeutic approach for ET patients.

Pretarsal blepharospasm: Clinical and electromyographic characteristics.

OBJECTIVE: To describe the clinical and electromyographic characteristics of blepharospasm caused by selective involvement of the pars pretarsalis of the orbicularis oculi muscle. METHODS: Clinical assessment and simultaneous electromyographic recordings from levator palpebrae superioris and pars orbitaria and pretarsalis of orbicularis oculi muscles were performed in patients with blepharospasm and primary failure to botulinum toxin injections. Patients with selective abnormal electromyographic activity of the pars pretarsalis of the orbicularis oculi muscle were identified and treated with selective pretarsal injections of botulinum toxin. RESULTS: We found 24 patients with pretarsal blepharospasm confirmed by the electromyographic assessment. All of them were functionally blind. Three clinical-electromyographic patterns were identified: (a) Impairment of eyelid opening; (b) Increased blinking; (c) Spasms of eye closure combined with varying degrees of excessive blinking and impairment of eye-opening. Pretarsal injections of botulinum toxin induced a significant improvement in all patients and 50 % regained normal or near-normal vision. The clinical improvement was sustained after repeated pretarsal injections. CONCLUSIONS: Pretarsal blepharospasm can be suspected on clinical grounds and it can be confirmed by electromyographic recordings. SIGNIFICANCE: Recognition of this type of blepharospasm is important because of its excellent response to botulinum toxin injections applied into the pretarsal part of the orbicularis oculi muscle.

Early Postural Instability in Parkinson's Disease: A Biomechanical Analysis of the Pull Test.

Postural instability in Parkinson's disease (PD) is commonly assessed by the pull test. This clinical test may be biased by the variability of the pull force applied. Our objective was to study the postural responses elicited by reproducible pull forces in healthy subjects and PD patients at different stages of the disease. We performed a multimodal approach that included a systematic analysis of the pull force needed to reach the backward limit of stability (FBLoS) assessed by mechanically produced forces, the displacements of the center of pressure (CoP) recorded on a force platform, and the latencies and patterns of activation of the stabilizing muscles. Comparisons between groups were performed by univariate and multivariate statistical analyses. Sixty-four healthy subjects and 32 PD patients, 22 Hoehn-Yahr (H-Y) stages I-II and 10 H-Y stage III, were studied. In healthy subjects, FBLoS decreased with aging and was lower in females. Mean (SD) FBLoS was 98.1 (48.9) Newtons (N) in healthy subjects, 70.5 (39.8) N in PD patients H-Y stages I-II, and 37.7 (18.9) N in PD patients H-Y stage III. Compared to healthy subjects and when adjusted for age and gender, PD patients H-Y stages I-II exhibited the following: (a) a reduced FBLoS; (b) larger CoP displacements and higher velocities for the same applied force; and (c) combined ankle and hip strategies elicited by less intense pull forces. All of these abnormalities were more pronounced in H-Y stage III PD patients compared to H-Y stages I-II PD patients. In conclusion, patients in the early stages of PD already exhibit a degree of postural instability due to inefficient postural adjustments, and they can more easily be destabilized by small perturbations than healthy subjects. This balance impairment becomes more pronounced in more advanced PD. In the pull test, pull force to step back should be a variable to consider when testing balance in clinical practice.

Kennedy disease with biphasic clinical course and rapid progression.

We report a case of spinal and bulbar muscular atrophy (SBMA), also known as Kennedy disease, with a 38 CAG-repeat expansion in exon-1 of the androgen receptor gene, presenting with a 2-year history of mild speech difficulty, dysphonia, and occasional choking. Initial clinical features and complementary studies were consistent with SBMA. The disease progression, as assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, remained stable over the first 5 years from the onset but showed a rapid decline (from 42 to 24 points) over the next 18 months before his death. In the later stages of the disease, deep tendon reflexes were preserved in limbs and a brisk jaw-jerk reflex and bilateral Hoffmann sign were evident. Survival from disease onset was 78 months. The final cause of death was aspiration pneumonia. The atypical clinical features, evolution, and accelerated disease course are not concordant with the relatively short 38 CAG-repeat expansion in the androgen receptor gene. This may represent either a variant SBMA phenotype, which has not been recorded to date, or the development of amyotrophic lateral sclerosis in a known case of SBMA.