Muscle Tone Physiology and Abnormalities.

The simple definition of tone as the resistance to passive stretch is physiologically a complex interlaced network encompassing neural circuits in the brain, spinal cord, and muscle spindle. Disorders of muscle tone can arise from dysfunction in these pathways and manifest as hypertonia or hypotonia. The loss of supraspinal control mechanisms gives rise to hypertonia, resulting in spasticity or rigidity. On the other hand, dystonia and paratonia also manifest as abnormalities of muscle tone, but arise more due to the network dysfunction between the basal ganglia and the thalamo-cerebello-cortical connections. In this review, we have discussed the normal homeostatic mechanisms maintaining tone and the pathophysiology of spasticity and rigidity with its anatomical correlates. Thereafter, we have also highlighted the phenomenon of network dysfunction, cortical disinhibition, and neuroplastic alterations giving rise to dystonia and paratonia.

A validated measure of rigidity in Parkinson's disease using alternating finger tapping on an engineered keyboard.

INTRODUCTION: Reliable and accurate measures of rigidity have remained elusive in remote assessments of Parkinson's disease (PD). This has severely limited the utility of telemedicine in the care and treatment of people with PD. It has also had a large negative impact on the scope of available outcomes, and on the costs, of multicenter clinical trials in PD. The goal of this study was to determine if quantitative measures from an engineered keyboard were sensitive and related to clinical measures of rigidity. METHODS: Sixteen participants with idiopathic PD, off antiparkinsonian medications, and eleven age-matched control participants performed a 30 second repetitive alternating finger tapping task on an engineered keyboard and were assessed with the Unified Parkinson's Disease Rating Scale - motor (UPDRS-III). RESULTS: The speed of the key release was significantly slower in the PD compared to control cohorts (p < 0.0001). In the PD cohort key release speed correlated with the lateralized upper extremity UPDRS III rigidity score (r = - 0.58, p < 0.0001), but not with the lateralized upper extremity tremor score (r = - 0.14, p = 0.43). CONCLUSIONS: This validated measure of rigidity complements our previous validation of temporal metrics of the repetitive alternating finger tapping task with the UPDRS III, bradykinesia and with the ability to quantify tremor, arrhythmicity and freezing episodes, and suggests that 30 seconds of alternating finger tapping on a portable engineered keyboard could transform the treatment of PD with telemedicine and the precision of multicenter clinical trials.

Paratonia in Dementia: A Systematic Review.

BACKGROUND: Paratonia is a dementia-induced motor abnormality. Although paratonia affects virtually all people with dementia, it is not well known among clinicians and researchers. OBJECTIVE: The aim of this study was to perform a systematic review of the literature on the definition, pathogenesis, diagnosis, and intervention of paratonia as well as to propose a research agenda for paratonia. METHODS: In this systematic review, the Embase, PubMed, CINAHL, and Cochrane CENTRAL databases were searched for articles published prior to December 2019. Two independent reviewers performed data extraction and assessed the risk of bias of the studies. The following data were extracted: first author, year of publication, study design, study population, diagnosis, assessment, pathogenesis, therapy and interventions. RESULTS: Thirty-five studies met the inclusion criteria and were included. Most studies included in the review mention clinical criteria for paratonia. Additionally, pathogenesis, method of assessment, diagnosis, and paratonia severity as are interventions to address paratonia are also discussed. CONCLUSION: This systematic review outlines what is currently known about paratonia, as well as discusses the preliminary research on the underlying mechanisms of paratonia. Although paratonia has obvious devastating impacts on health and quality of life, the amount of research to date has been limited. In the last decade, there appears to have been increased research on paratonia, which hopefully will increase the momentum to further advance the field.

The evolution of parkinsonism in primary progressive apraxia of speech: A 6-year longitudinal study.

INTRODUCTION: Primary progressive apraxia of speech (PPAOS) is a neurodegenerative syndrome in which patients present with an isolated motor speech disorder. Some PPAOS patients develop parkinsonism and other features of progressive supranuclear palsy (PSP) and/or corticobasal syndrome (CBS) over time. We aimed to assess the evolution of parkinsonian characteristics in PPAOS patients who had been followed yearly for at least six years. METHODS: From a large cohort of 46 PPAOS patients, eight were followed yearly for > 6-years in multiple NIH-funded grants. Parkinsonian and other features, including bradykinesia, tremor, rigidity, postural instability, apraxia, ocular motor function and cognition were assessed at each visit, and research criteria applied for PSP and CBS diagnosis. Neurological, speech-language test scores, and [18F]fluorodeoxyglucose PET (FDG-PET) and MRI midbrain volumes were assessed. RESULTS: A Parkinson's plus syndrome developed in all eight patients (100%). Bradykinesia was the earliest feature, followed by rigidity and postural instability. Tremor was not a significant feature. Parkinsonism, limb apraxia and ocular motor impairment tended to develop four-to-five years after onset with some patients having slight asymmetric parkinsonism. Six patients (75%) met research criteria for probable PSP, although only one for PSP-Richardson's syndrome; three patients met criteria for possible CBS. Slightly asymmetric, left-sided, hypometabolism was observed on FDG-PET, not matching asymmetry of Parkinsonism. Midbrain hypometabolism was absent-minimal. Three patients had progressive midbrain volumes in the PSP-Richardson's syndrome range. CONCLUSIONS: A Parkinson's plus syndrome may inevitably develop in PPAOS supporting PPAOS as an early presentation of a Parkinson's plus disorder.

Acute hypokinetic-rigid syndrome following SARS-CoV-2 infection.

OBJECTIVE: To report a case of a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who acutely developed a hypokinetic-rigid syndrome. METHODS: Patient data were obtained from medical records from the Hospital Universitario 12 de Octubre in Madrid, Spain. [123I]-ioflupane dopamine transporter (DaT) SPECT images were acquired 4 hours after a single dose of 185 MBq of 123I-FP-CIT. Quantitative analysis was performed with DaTQUANT software providing the specific binding ratio and z score values of the striatum. RESULTS: We report a previously healthy 58-year-old man who developed hyposmia, generalized myoclonus, fluctuating and transient changes in level of consciousness, opsoclonus, and an asymmetric hypokinetic-rigid syndrome with ocular abnormalities after a severe SARS-CoV-2 infection. DaT-SPECT confirmed a bilateral decrease in presynaptic dopamine uptake asymmetrically involving both putamina. Significant improvement in the parkinsonian symptoms was observed without any specific treatment. CONCLUSION: This case study provides clinical and functional neuroimaging evidence to support that SARS-CoV-2 can gain access to the CNS, affecting midbrain structures and leading to neurologic signs and symptoms.

Static and dynamic postural control: Comparison between community old adults and people with Parkinson's disease.

AIMS: To compare the static and dynamic postural control of people with Parkinson's disease and community old adults. METHODS: Thirty-five people were in the Parkinson's disease group (PDG; 12 women, 62.4 ± 11.0 years, 77.9 ± 15.6 kg, 166.5 ± 11.0 cm, 27.9 ± 3.8 kg/m2 , 1.9 ± 0.5 Hoehn & Yahr) and 32 were in the old adults group (OAG; 13 women, 69.5 ± 6.0 years, 74.2 ± 12.3 kg, 165.0 ± 8.3 cm, 27.2 ± 4.0 kg/m2 ). The static balance was measured on a force platform, three 30-s trials in four conditions: feet side-by-side (FSBS) and semi-tandem stance (ST) positioning, eyes open (EO) and eyes closed (EC). The total sway path length (SPL), sway area (SA), anterior-posterior (APSR) and medial-lateral (MLSR) sway range of the centre of pressure were obtained. Dynamic balance was assessed using the timed-up-and-go test (TUG). For comparison between groups and repeated-measures, a mixed-design ANOVA was carried out and the Mann-Whitney U test to compare TUG between groups. The significance level was set at p ≤ .05. RESULTS: Between groups, PDG presented higher mean values for SPL, APSR and SA in feet side-by-side eyes open compared to the OAG, for SPL in feet side-by-side eyes closed, for SPL and SA in STEO. For repeated-measures, both groups had higher mean values in the EC condition compared to EO and MLSR compared to APSR. No significant difference was found between groups for TUG. CONCLUSION: Balance disorders are found early in people with Parkinson's disease compared to healthy older adults. Thus, Parkinson's disease seems to advance the process of alterations in the postural control system.

REM sleep without atonia is associated with increased rigidity in patients with mild to moderate Parkinson's disease.

OBJECTIVE: Increased muscle activity during rapid eye movement (REM) sleep (i.e. REM sleep without atonia) is common in people with Parkinson's disease (PD). This study tested the hypotheses that people with PD and REM sleep without atonia (RSWA) would present with more severe and symmetric rigidity compared to individuals with PD without RSWA and age-matched controls. METHODS: Sixty-one individuals participated in this study (41 PD, 20 controls). An overnight sleep study was used to classify participants with PD as having either elevated (PD-RSWA+) or normal muscle activity (PD-RSWA-) during REM sleep. Quantitative measures of rigidity were obtained using a robotic manipulandum that passively pronated and supinated the forearm. RESULTS: Quantitative measures of forearm rigidity were significantly higher in the PD-RSWA+ group compared to the control group. Rigidity was significantly more asymmetric between limbs in the PD-RSWA- group compared with controls, while there was no significant difference in symmetry between the control and PD-RSWA+ groups. CONCLUSION: In people with mild to moderate PD, RSWA is associated with an increased and more symmetric presentation of upper limb rigidity. SIGNIFICANCE: Dysfunction of brainstem systems that control muscle tone during REM sleep may contribute to increased rigidity during wakefulness in people with PD.

Substantia Nigra Volume Dissociates Bradykinesia and Rigidity from Tremor in Parkinson's Disease: A 7 Tesla Imaging Study.

BACKGROUND: In postmortem analysis of late stage Parkinson's disease (PD) neuronal loss in the substantial nigra (SN) correlates with the antemortem severity of bradykinesia and rigidity, but not tremor. OBJECTIVE: To investigate the relationship between midbrain nuclei volume as an in vivo biomarker for surviving neurons in mild-to-moderate patients using 7.0 Tesla MRI. METHODS: We performed ultra-high resolution quantitative susceptibility mapping (QSM) on the midbrain in 32 PD participants with less than 10 years duration and 8 healthy controls. Following blinded manual segmentation, the individual volumes of the SN, subthalamic nucleus, and red nucleus were measured. We then determined the associations between the midbrain nuclei and clinical metrics (age, disease duration, MDS-UPDRS motor score, and subscores for bradykinesia/rigidity, tremor, and postural instability/gait difficulty). RESULTS: We found that smaller SN correlated with longer disease duration (r = -0.49, p = 0.004), more severe MDS-UPDRS motor score (r = -0.42, p = 0.016), and more severe bradykinesia-rigidity subscore (r = -0.47, p = 0.007), but not tremor or postural instability/gait difficulty subscores. In a hemi-body analysis, bradykinesia-rigidity severity only correlated with SN contralateral to the less-affected hemi-body, and not contralateral to the more-affected hemi-body, possibly reflecting the greatest change in dopamine neuron loss early in disease. Multivariate generalized estimating equation model confirmed that bradykinesia-rigidity severity, age, and disease duration, but not tremor severity, predicted SN volume. CONCLUSIONS: In mild-to-moderate PD, SN volume relates to motor manifestations in a motor domain-specific and laterality-dependent manner. Non-invasive in vivo 7.0 Tesla QSM may serve as a biomarker in longitudinal studies of SN atrophy and in studies of people at risk for developing PD.

Quantitative Measurement of Rigidity in Parkinson´s Disease: A Systematic Review.

Rigidity is one of the cardinal symptoms of Parkinson´s disease (PD). Present in up 89% of cases, it is typically assessed with clinical scales. However, these instruments show limitations due to their subjectivity and poor intra- and inter-rater reliability. To compile all of the objective quantitative methods used to assess rigidity in PD and to study their validity and reliability, a systematic review was conducted using the Web of Science, PubMed, and Scopus databases. Studies from January 1975 to June 2019 were included, all of which were written in English. The Strengthening the Reporting of observational studies in Epidemiology Statement (STROBE) checklist for observational studies was used to assess the methodological rigor of the included studies. Thirty-six studies were included. Rigidity was quantitatively assessed in three ways, using servomotors, inertial sensors, and biomechanical and neurophysiological study of muscles. All methods showed good validity and reliability, good correlation with clinical scales, and were useful for detecting rigidity and studying its evolution. People with PD exhibit higher values in terms of objective muscle stiffness than healthy controls. Rigidity depends on the angular velocity and articular amplitude of the mobilization applied. There are objective, valid, and reliable methods that can be used to quantitatively assess rigidity in people with PD.

Electrophysiological resting state networks of predominantly akinetic-rigid Parkinson patients: Effects of dopamine therapy.

Parkinson's disease (PD) causes both motor and non-motor symptoms, which can partially be reversed by dopamine therapy. These symptoms as well as the effect of dopamine may be explained by distinct alterations in whole-brain architecture. We used functional connectivity (FC) and in particular resting state network (RSN) analysis to identify such whole-brain alterations in a frequency-specific manner. In addition, we hypothesized that standard dopaminergic medication would have a normalizing effect on these whole brain alterations. We recorded resting-state EEGs of 19 PD patients in the medical OFF and ON states, and of 12 healthy age-matched controls. The PD patients were either of akinetic-rigid or mixed subtype. We extracted RSNs with independent component analysis in the source space for five frequency bands. Within the sensorimotor network (SMN) the supplementary motor area (SMA) showed decreased FC in the OFF state compared to healthy controls. This finding was reversed after dopamine administration. Furthermore, in the OFF state no stable SMN beta component could be identified. The default mode network showed alterations due to PD independent of the medication state. The visual network was altered in the OFF state, and reinstated to a pattern similar to healthy controls by medication. In conclusion, PD causes distinct RSN alterations, which are partly reversed after levodopa administration. The changes within the SMN are of particular interest, because they broaden the pathophysiological understanding of PD. Our results identify the SMA as a central network hub affected in PD and a crucial effector of dopamine therapy.

Demographic characteristics and delayed neurological sequelae risk factors in carbon monoxide poisoning.

AIM: Carbon monoxide (CO) is a colorless, odorless gas and tasteless. CO poisoning (COP) is one of the most frequently encountered inhalation poisonings. The most common cause of morbidity in COP is delayed neurological sequelae (DNS). DNS is the occurrence of neuropsychiatric findings within 2-240 days after discharge of patients with COP and there are no definitive diagnostic criteria. The aim of our study is; to determine the risk factors and incidence of DNS. METHOD: Our study is a retrospective, observational study. Patients with the diagnosis of COP in the emergency department between 2015 and 2016 were included in the study. Patients age, gender, findings in the initial physical examination (PE) and neurological examination (NE), blood carboxyhemoglobin (COHb) level, relation between hyperbaric oxygen (HBO) treatment and DNS were assessed. RESULTS: Total of 72 patients were included in the study. Mean age was 33.43 ±â€¯20.89. It was determined that pathological findings in the initial NE are a significant predictive factor for DNS (Odds ratio 18.600, p:0.004). Significant relation between NE and HBO treatment was present (p:00.1). There was no statistically significant relationship between initial COHb level and receiving HBO treatment (p:0.9). Median COHb level of patients with DNS was 30 (min:10, max: 43), median COHb level of patients without DNS was 25 (min:10, max:44) and there was no statistically significant relationship between the two groups according to COHb levels (p:0.7). CONCLUSION: Pathological findings in the initial neurological examination had a predictive value for delayed neurological sequelae in patients with carbon monoxide poisoning.

Management of Dysphagia in Patients with Parkinson's Disease and Related Disorders.

Various methods of rehabilitation for dysphagia have been suggested through the experience of treating stroke patients. Although most of these patients recover their swallowing function in a short period, dysphagia in Parkinson's disease (PD) and Parkinson-related disorder (PRD) degenerates with disease progression. Muscle rigidity and bradykinesia are recognized as causes of swallowing dysfunction, and it is difficult to easily apply the strategies for stroke to the rehabilitation of dysphagia in PD patients. Disease severity, weight loss, drooling, and dementia are important clinical predictors. Silent aspiration is a pathognomonic sign that may lead to aspiration pneumonia. Severe PD patients need routine video fluoroscopy or video endoscopy to adjust their food and liquid consistency. Patients with PRD experience rapid progression of swallowing dysfunction. Nutrition combined with nasogastric tube feeding or percutaneous endoscopic gastrostomy feeding should be considered owing to the increased risk of aspiration and difficulty administrating oral nutrition.

Stiff limb syndrome with lower limb myoclonus: A case report.

RATIONALE: stiff limb syndrome (SLS) is a variant of stiff-man syndrome, primarily affecting a specific limb. Its diagnosis has always been challenging due to the lack of a specific confirmation test. We present a rare case of a patient with lower limb myoclonus and rigidity. PATIENT CONCERNS: A 53-year-old male presented with a sudden onset of progressive left lower extremity myoclonus and muscle rigidity for 3 days. He rapidly showed signs of right lower limb involvement with severe joint stiffness and inability to walk. DIAGNOSIS: The symptoms nature, physical examination, careful elimination of differential diagnosis suggested a diagnosis of stiff limb syndrome. INTERVENTIONS: Intravenous infusion of gamma globulin 0.4 mg/kg coupled with baclofen and clonazepam were given after admission. He also received an injection of botulinum toxin A to relieve his muscle stiffness. OUTCOMES: The patients' condition improved after the initial treatment with complete disappearance of muscle twitching. Further improvements were seen later on after the local administration of botulinum toxin A. LESSONS: Stiff limb syndrome shares the same complex symptoms with many other conditions. Its diagnosis relies heavily on clinical presentations and on ruling out other conditions. However, unusual symptoms such as myoclonus can occur in few cases and together with the rarity of the condition, the prevalence of misdiagnosis is high. Therefore, being aware and recognizing the signs and symptoms is crucial for proper management. Additionally, EMG is a very important test if the present condition is suspected. However, a negative EMG result or a negative anti-glutamic acid decarboxylase antibody test should not exclude SLS diagnosis.

Washout of chronic therapeutic deep brain stimulation increases cortical phase-amplitude coupling.

Invasive human brain recordings have shown that acute therapeutic deep brain stimulation (DBS) reduces cortical synchronization, measured by coupling of beta phase to gamma amplitude. Here we show by noninvasive scalp electroencephalography that withdrawal of chronic DBS elevates phase-amplitude coupling, in proportion to the worsening of contralateral rigidity.

Prospective memory in Parkinson's disease: the role of the motor subtypes.

BACKGROUND: Prospective memory (PM) is defined as memory for future intentions and it is typically divided into time-based and event-based PM. Deficit of PM has been reported in patients with Parkinson's disease (PD) but no study has yet explored the association between motor subtypes (tremor dominant and rigidity/bradykinesia dominant) and performance on PM tasks. The aim of the study was to explore the role of motor subtypes in the defect of PM. METHODS: Consecutive outpatients with tremor dominant (TD-PD) or rigidity/bradykinesia dominant (PIGD-PD) PD and healthy subjects (HCs) were enrolled and underwent a neuropsychological battery assessing PM, verbal memory and executive functions and questionnaires assessing apathy, functional autonomy, and perceived memory disturbances. RESULTS: We enrolled 28 patients with TD-PD, 28 patients with PIGD-PD and 50 HCs. The three groups did not differ on demographic and cognitive variables. Patients with TD-PD performed worse on time-based PM tasks than patients with PIGD-PD and HCs; no significant difference was found among the three groups on event-based PM tasks. Executive dysfunctions contributed to reduced time-based PM scores in TD-PD. Moreover, severe deficit of time-based and more frequency of perceived failures of PM contributed to reduced functional autonomy in TD-PD. CONCLUSION: The finding of a poorer performance of patients with TD-PD than ones with PIGD-PD and HCs suggests a selective deficit of time-based PM abilities in TD-PD group; therefore, deficit of time-based PM might be considered as a distinctive non-motor symptom of TD-PD and it might affect the functional autonomy in this subtype of PD.

Responses to anterior and posterior perturbations in Parkinson's disease with early postural instability: role of axial and limb rigidity.

We studied 12 patients with Parkinson's disease (PD): 6 with postural instability (Hoehn and Yahr Stage 3) and 6 without (Stage 2 or 2.5), using a quantitative test based on the clinical pull test. Their findings were compared with those for 12 healthy controls. The patients on their usual medications were pulled either forwards or backwards at the level of the shoulders and asked not to take a step in a series of five trials. Acceleration was monitored for the upper trunk, sacrum, and both tibias. EMG was measured in soleus and tibialis anterior (TA) muscles in all and for thigh and truncal muscles in a subgroup. A target of 0.2 g trunk acceleration was used, but smaller perturbations were used in very unstable patients. All the Stage 3 patients lost balance in at least one trial for the posterior perturbations but none for the anterior ones. None of the Stage 2 patients lost balance. There was increased tonic EMG and agonist activity but no difference in EMG onset or initial force production compared to healthy controls. For posterior perturbations, there were two related disorders that separated the PD patients from controls. There was a significantly higher ratio of sacral-to-applied acceleration and both PD groups showed reduced knee acceleration and shortened latency, more so for the Stage 3 group. The increased sacral-to-C7 acceleration ratio was correlated with the tonic level of activation of the hamstrings (HS), quadriceps, and lumbar paraspinal muscles (PS), while the tibial acceleration latency was also correlated with the level of tonic PS activation. We also found that the size of balance responses, 0-200 ms post-perturbation, correlated significantly with the level of tonic activation in nearly all the muscles studied. We confirmed that PD patients show greater instability posteriorly than anteriorly to applied perturbations. Our findings support increasing axial and limb rigidity as the cause of the impaired pull test rather than postural bradykinesia and suggest that tonic truncal and thigh muscle activation may be an important underlying cause.