Wearable Accelerometer and Gyroscope Sensors for Estimating the Severity of Essential Tremor.

BACKGROUND: Several validated clinical scales measure the severity of essential tremor (ET). Their assessments are subjective and can depend on familiarity and training with scoring systems. METHOD: We propose a multi-modal sensing using a wearable inertial measurement unit for estimating scores on the Fahn-Tolosa-Marin tremor rating scale (FTM) and determine the classification accuracy within the tremor type. 17 ET participants and 18 healthy controls were recruited for the study. Two movement disorder neurologists who were blinded to prior clinical information viewed video recordings and scored the FTM. Participants drew a guided Archimedes spiral while wearing an inertial measurement unit placed at the mid-point between the lateral epicondyle of the humerus and the anatomical snuff box. Acceleration and gyroscope recordings were analyzed. The ratio of the power spectral density between frequency bands 0.5-4 Hz and 4-12 Hz, and the sum of power spectrum density over the entire spectrum of 2-74 Hz, for both accelerometer and gyroscope data, were computed. FTM was estimated using regression model and classification using SVM was validated using the leave-one-out method. RESULTS: Regression analysis showed a moderate to good correlation when individual features were used, while correlation was high ([Formula: see text] = 0.818) when suitable features of the gyro and accelerometer were combined. The accuracy for two-class classification of the combined features using SVM was 91.42% while for four-class it was 68.57%. CONCLUSION: Potential applications of this novel wearable sensing method using a wearable Inertial Measurement Unit (IMU) include monitoring of ET and clinical trials of new treatments for the disorder.

Wearable sensors during drawing tasks to measure the severity of essential tremor.

Commonly used methods to assess the severity of essential tremor (ET) are based on clinical observation and lack objectivity. This study proposes the use of wearable accelerometer sensors for the quantitative assessment of ET. Acceleration data was recorded by inertial measurement unit (IMU) sensors during sketching of Archimedes spirals in 17 ET participants and 18 healthy controls. IMUs were placed at three points (dorsum of hand, posterior forearm, posterior upper arm) of each participant's dominant arm. Movement disorder neurologists who were blinded to clinical information scored ET patients on the Fahn-Tolosa-Marin rating scale (FTM) and conducted phenotyping according to the recent Consensus Statement on the Classification of Tremors. The ratio of power spectral density of acceleration data in 4-12 Hz to 0.5-4 Hz bands and the total duration of the action were inputs to a support vector machine that was trained to classify the ET subtype. Regression analysis was performed to determine the relationship of acceleration and temporal data with the FTM scores. The results show that the sensor located on the forearm had the best classification and regression results, with accuracy of 85.71% for binary classification of ET versus control. There was a moderate to good correlation (r2 = 0.561) between FTM and a combination of power spectral density ratio and task time. However, the system could not accurately differentiate ET phenotypes according to the Consensus classification scheme. Potential applications of machine-based assessment of ET using wearable sensors include clinical trials and remote monitoring of patients.

The Thermodynamic Consequences of Parkinson's Disease.

Several lines of evidence point to a pervasive disturbance of energy balance in Parkinson's disease (PD). Weight loss, common and multifactorial, is the most observable sign of this. Bradykinesia may be best understood as an underinvestment of energy in voluntary movement. This accords with rodent experiments that emphasise the importance of dopamine in allocating motor energy expenditure. Oxygen consumption studies in PD suggest that, when activities are standardised for work performed, these inappropriate energy thrift settings are actually wasteful. That the dopaminergic deficit of PD creates a problem with energy efficiency highlights the role played by the basal ganglia, and by dopamine, in thermodynamic governance. This involves more than balancing energy, since living things maintain their internal order by controlling transformations of energy, resisting probabilistic trends to more random states. This review will also look at recent research in PD on the analysis of entropy-an information theory metric of predictability in a message-in recordings from the basal ganglia. Close relationships between energy and information converge around the concept of entropy. This is especially relevant to the motor system, which regulates energy exchange with the outside world through its flow of information. The malignant syndrome in PD, a counterpart of neuroleptic malignant syndrome, demonstrates how much thermodynamic disruption can result from breakdown of motor signalling in an extreme hypodopaminergic state. The macroenergetic disturbances of PD are consistent with a unifying hypothesis of dopamine's neurotransmitter actions-to adapt energy expenditure to prevailing economic circumstances.

Computerised analysis of writing and drawing by essential tremor phenotype.

We investigated whether computerised analysis of writing and drawing could discriminate essential tremor (ET) phenotypes according to the 2018 Consensus Statement on the Classification of Tremors. The Consensus scheme emphasises soft additional findings, mainly motor, that do not suffice to diagnose another tremor syndrome. Ten men and nine women were classified by blinded assessors according to Consensus Axis 1 definitions of ET and ET plus. Blinded scoring of tremor severity and alternating limb movement was also conducted. Twenty healthy participants acted as controls. Four writing and three drawing tasks were performed on a Wacom Intuos Pro Large digital tablet with a pressure-sensor mounted ink pen. Sixty-seven computerised measurements were obtained, comprising static (dimensional and temporal), kinematic and pen pressure features. The mean age of ET participants was 67.2±13.0 years and mean tremor duration was 21.7±19.0 years. Six were classified as ET, five had one plus feature and eight had two plus features. The computerised analysis could predict the presence and number of ET plus features. Measures of acceleration and variation of pen pressure performed strongly to separate ET phenotypes (p<0.05). Plus features were associated with higher scores on the Fahn-Tolosa-Marin Tremor Rating Scale (p=0.001) and it appeared that ET groups were mainly being separated according to severity of tremor and by compensatory manoeuvres used by participants with more severe tremor. There were, in addition, a small number of negative kinematic correlations suggesting some slowness with ET plus. Abnormal repetitive limb movement was also correlated with tremor severity (R=0.57) by clinical grading. Critics of the Consensus Statement have drawn attention to weaknesses of the ET plus concept in relation to duration and severity of ET. This classification of ET may be too biased towards tremor severity to assist in distinguishing underlying biological differences by clinical measurement.

Movement disorders in psychiatric patients.

The observability of movement gives it advantages when trying to draw connections between brain and mind. Disturbed motor function pervades schizophrenia, though it is difficult now to subtract the effects of antipsychotic treatment. There is evidence from patients never exposed to these drugs that dyskinesia and even parkinsonism are to some degree innate to schizophrenia. Tardive dyskinesia and drug-induced parkinsonism are the most common movement disorders encountered in psychiatric practice. While D2 dopamine receptor blockade is a causative factor, both conditions defy straightforward neurochemical explanation. Balanced against the need to manage schizophrenic symptoms, neither prevention nor treatment is easy. Of all disorders classified as psychiatric, catatonia sits closest to organic neurology on the neuropsychiatric spectrum. Not only does it occur in the setting of unequivocally organic cerebral disease, but the alterations of consciousness it produces have 'organic' qualities even when the cause is psychiatric. No longer considered a subtype of schizophrenia, catatonia is defined by syndromic features based on motor phenomenology. Both severe depression and obsessive-compulsive disorder may be associated with 'soft' extrapyramidal signs that resemble parkinsonian bradykinesia. As functional neuroimaging studies suggest, movement and psychiatric disorders involve the same network connections between the basal ganglia and the cerebral cortex.

Arytenoid cartilage movements are hypokinetic in Parkinson's disease: A quantitative dynamic computerised tomographic study.

BACKGROUND: Voice change is one of the earliest features of Parkinson's disease. However, quantitative studies of vocal fold dynamics which are needed to provide insight into disease biology, aid diagnosis, or track progression, are few. METHODS: We therefore quantified arytenoid cartilage movements and glottic area during repeated phonation in 15 patients with Parkinson's disease (symptom duration < 6 years) and 19 controls, with 320-slice computerised tomography (CT). We related these measures to perceptual voice evaluations and spirometry. We hypothesised that Parkinson's disease patients have a smaller inter-arytenoid distance, a preserved or larger glottic area because vocal cord bowing has previously been reported, less variability in loudness, more voice dysdiadochokinesis and breathiness and a shortened phonation time because of arytenoid hypokinesis relative to glottic area. RESULTS: Inter-arytenoid distance in Parkinson's disease patients was moderately smaller (Mdn = 0.106, IQR = 0.091-0.116) than in controls (Mdn = 0.132, IQR = 0.116-0.166) (W = 212, P = 0.015, r = -0.42), normalised for anatomical and other inter-subject variance, analysed with two-tailed Wilcoxon's rank sum test. This finding was confirmed in a linear mixed model analysis-Parkinson's disease significantly predicted a reduction in the dependent variable, inter-arytenoid distance (b = -0.87, SEb = 0.39, 95% CI [-1.66, -0.08], t(31) = -2.24, P = 0.032). There was no difference in glottic area. On perceptual voice evaluation, patients had more breathiness and dysdiadochokinesis, a shorter maximum phonation time, and less variability in loudness than controls. There was no difference in spirometry after adjustment for smoking history. CONCLUSIONS: As predicted, vocal fold adduction movements are reduced in Parkinson's disease on repeated phonation but glottic area is maintained. Some perceptual characteristics of Parkinsonian speech reflect these changes. We are the first to use 320-slice CT to study laryngeal motion. Our findings indicate how Parkinson's disease affects intrinsic laryngeal muscle position and excursion.

Progressive Dopamine Transporter Binding Loss in Autopsy-Confirmed Corticobasal Degeneration.

BACKGROUND: Corticobasal degeneration (CBD) is characterized by neuronal and glial deposition of 4-repeat tau in the frontal and parietal cerebral cortex, white matter and striatum. There is neuronal loss in affected cortical regions and in the substantia nigra (SN). Recent single photon emission tomography (SPECT) studies have reported normal striatal dopamine transporter (DAT) binding in individual patients with CBD. OBJECTIVE: To study the pattern and course of DAT binding loss in CBD. METHODS: We retrospectively analyzed DAT SPECT studies in two patients presenting with a corticobasal syndrome in whom a diagnosis of CBD was later confirmed pathologically. RESULTS: Baseline scans at 1.5 years after symptom onset revealed only mild abnormalities (reduced uptake in one putamen). Follow up scans at 4.5 years (Case 1) and 5 years (Case 2) after symptom onset showed a marked decline of striatal DAT binding. In both cases, there was a 37% binding reduction from the age-expected striatal binding value. Asymmetry of striatal DAT binding had increased from mild in the first SPECT studies to moderate at the time of their final imaging. CONCLUSION: CBD patients can have delayed neuronal loss in the SN. Follow up DAT imaging may be of value in patients with possible CBD and a normal baseline scan.

Correlation of striatal dopamine transporter imaging with post mortem substantia nigra cell counts.

Dopamine transporter imaging is widely used for the differential diagnosis of parkinsonism. Only limited data are available on the relationship between striatal dopamine transporter binding and dopaminergic cell loss in the substantia nigra (SN). We analyzed postmortem SN cell counts in patients who had previously undergone dopamine transporter single-photon emission computed tomography (SPECT). Pathological diagnoses included Parkinson's disease (n = 1), dementia with Lewy bodies (n = 2), multiple system atrophy (n = 1), corticobasal degeneration (n = 2), atypical parkinsonism with multiple pathological conditions (n = 1), Alzheimer's disease (n = 1), and Creutzfeldt-Jakob disease (n = 1). [(12) (3) I]ß-CIT SPECT had been performed in all subjects using a standardized protocol on the same triple-head gamma camera. The density of neuromelanin-containing and tyrosine hydroxylase-positive substantia nigra neurons/mm(2) was evaluated in paraffin-embedded tissue sections by morphometric methods. Mean disease duration at the time of dopamine transporter imaging was 2.3 years, and the mean interval from imaging to death was 29.3 months (range, 4-68 months). Visual analysis of dopamine transporter images showed reduced striatal uptake in all seven patients with neurodegenerative parkinsonism, but not in Alzheimer's and Creutzfeldt-Jakob disease cases. Averaged [(right+left)/2] striatal uptake was highly correlated with averaged SN cell counts (rs = 0.98, P < 0.0005 for neuromelanin- and rs = 0.96, P < 0.0005 for tyrosine hydroxylase-positive cells). Similar strong correlations were found in separate analyses for the right and left sides. Striatal dopamine transporter binding highly correlated with postmortem SN cell counts, confirming the validity of dopamine transporter imaging as an excellent in vivo marker of nigrostriatal dopaminergic degeneration.

Intracellular processing of disease-associated α-synuclein in the human brain suggests prion-like cell-to-cell spread.

Dementia with Lewy bodies (DLB), Parkinson's disease (PD) and multiple system atrophy are characterized by the deposition of disease-associated α-synuclein. In the present study we 1) examined the molecular specificity of the novel anti-α-synuclein 5G4 antibody; 2) evaluated immunoreactivity patterns and their correlation in human brain tissue with micro- and astrogliosis in 57 cases with PD or DLB; and 3) performed a systematic immunoelectron microscopical mapping of subcellular localizations. 5G4 strongly binds to the high molecular weight fraction of ß-sheet rich oligomers, while no binding to primarily disordered oligomers or monomers was observed. We show novel localizations of disease-associated α-synuclein including perivascular macrophages, ependyma and cranial nerves. α-Synuclein immunoreactive neuropil dots and thin threads associate more with glial reaction than Lewy bodies alone. Astrocytic α-synuclein is an important component of the pathology. Furthermore, we document ultrastructurally the pathway of processing of disease-associated α-synuclein within neurons and astroglial cells. Interaction of mitochondria and disease-associated α-synuclein plays a key role in the molecular-structural cytopathogenesis of disorders with Lewy bodies. We conclude that 1) the 5G4 antibody has strong selectivity for ß-sheet rich α-synuclein oligomers; 2) Lewy bodies themselves are not the most relevant morphological substrate that evokes tissue lesioning; 3) both neurons and astrocytes internalize disease-associated α-synuclein in the human brain, suggesting prion-like cell-to-cell spread of α-synuclein by uptake from surrounding structures, as shown previously in experimental observations.

Cerebrovascular profile assessment in Parkinson's disease patients.

INTRODUCTION: Parkinson's disease (PD) is one of the most common neurodegenerative diseases, and PD patients can present a variety of comorbidities that increase with age. Among them, cardiovascular and cerebrovascular diseases are the most prominent. AIM: To assess the cardiovascular and cerebrovascular profiles of PD patients. PATIENTS AND METHODS: The cardiovascular risk factors of 126 PD patients were assessed according to laboratory tests (fasting blood sugar, serum cholesterol, triglycerides, and total lipids), Doppler ultrasound examinations and personal histories of cerebrovascular disease (ischemic/hemorrhagic), cardiovascular disease (myocardial infarct or angina confirmed by electrocardiogram), hypertension and diabetes. All patients underwent cerebral structural imaging procedures: computed tomography or magnetic resonance imaging. RESULTS: 58.73% of the patients presented with hypertension, with a slight predominance of female patients (65.38% vs 47.92%, P = 0.05). Carotid or vertebral atheromatosis was present in 39 (30.95%) and 28 (22.22%) of patients, respectively, and was statistically correlated with the presence of ischemic lesions on cerebral imaging. Regarding the computed tomography findings, 33 patients (28.21%) presented with cortical atrophy that was not correlated with any of the investigated cardiovascular factors. CONCLUSIONS: Our findings indicate that risk factors for cardiovascular and cerebrovascular diseases are common in PD patients, possibly due to their older age. The presence of atherosclerosis and its complications can be detected in cerebral imaging studies.

Delayed postirradiation camptocormia.

Radiotherapy may cause central or peripheral nervous system complications, reported examples being myelopathy, brachial/lumbosacral plexopathies or predominantly motor lumbosacral radiculopathy. In the literature some studies regard camptocormia as a paravertebral myopathy and others as of neurogenic origin. We present a patient who developed camptocormia, 42 years after radiation therapy to the para-aortic and inguinal area.

Dopamine D2 receptor SPECT in corticobasal syndrome and autopsy-confirmed corticobasal degeneration.

BACKGROUND: Corticobasal degeneration (CBD) is a rare neurodegenerative disorder characterized by tau-positive neuronal and glial lesions in the cortex and striatum with neuronal loss in cortical regions and in the substantia nigra. Striatal dopamine D2 receptor binding in autopsy-confirmed CBD has not been studied before. METHODS: We performed D2 receptor single photon emission computerized tomography using (123)I-IBZM in nine patients with a clinically diagnosed corticobasal syndrome (CBS) and on ten healthy controls. Two of the patients subsequently came to autopsy and were diagnosed with CBD. RESULTS: Overall striatal D2 receptor binding was preserved in 8/9 patients, but more asymmetric than in controls. Overall striatal binding in pathologically confirmed CBD was reduced in one case and normal in the other, and was lower contralateral to the clinically more affected side in both. CONCLUSION: This first study on D2 receptor imaging in autopsy-confirmed CBD demonstrates that loss of postsynaptic striatal neurons in CBD is a variable finding. Given the heterogeneity of our findings in pathology-confirmed cases, D2 receptor imaging seems to be of little practical value in the diagnostic workup of patients with CBS.

Dopamine transporter imaging in autopsy-confirmed Parkinson's disease and multiple system atrophy.

Dopamine transporter single-photon emission computerized tomography can visualize dopaminergic degeneration in Parkinson's disease and multiple system atrophy. Some studies have suggested that dopamine transporter imaging can distinguish these disorders based on a more diffuse and symmetric striatal dopamine transporter binding loss in multiple system atrophy. The present study compared patterns of striatal dopamine transporter distribution in postmortem-confirmed Parkinson's disease and multiple system atrophy. Patients with a postmortem diagnosis of multiple system atrophy (n = 6) or Parkinson's disease (n = 8) who had undergone dopamine transporter imaging were included. Imaging had been performed after a mean disease duration of 3.6 and 4.1 years in multiple system atrophy and Parkinson's disease, respectively. Visual analysis showed bilaterally reduced binding in all patients. Mean overall striatal binding was reduced by 53% in multiple system atrophy and 52% in Parkinson's disease. There was a trend for greater asymmetry of striatal binding in multiple system atrophy compared with Parkinson's disease (23% ± 15% vs 10.5% ± 7%, respectively; P = .071), with 3 multiple system atrophy patients showing more asymmetry of striatal binding than any Parkinson's disease patient. Putamen/caudate binding ratios did not differ between the groups. This is the first study comparing dopamine transporter imaging in autopsy-confirmed multiple system atrophy and Parkinson's disease. Unexpectedly, we found a tendency for greater asymmetry of striatal binding in multiple system atrophy than in Parkinson's disease. Our findings demonstrate that these conditions cannot be differentiated by subregional analysis of striatal dopamine transporter binding.