Multisystemic RFC1-Related Disorder: Expanding the Phenotype Beyond Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome.

Background and Objectives: The RFC1 spectrum has become considerably expanded as multisystemic features beyond the triad of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) have started to be unveiled, although many still require clinical replication. Here, we aimed to clinically characterize a cohort of RFC1-positive patients by addressing both classic and multisystemic features. In a second part of this study, we prospectively assessed small nerve fibers (SNF) and autonomic function in a subset of these RFC1-related patients. Methods: We retrospectively enrolled 67 RFC1-positive patients from multiple neurologic centers in Portugal. All patients underwent full neurologic and vestibular evaluation, as well as neuroimaging and neurophysiologic studies. For SNF and autonomic testing (n = 15), we performed skin biopsies, quantitative sensory testing, sudoscan, sympathetic skin response, heart rate deep breathing, and tilt test. Results: Multisystemic features beyond CANVAS were present in 82% of the patients, mainly chronic cough (66%) and dysautonomia (43%). Other features included motor neuron (MN) affection and motor neuropathy (18%), hyperkinetic movement disorders (16%), sleep apnea (6%), REM and non-REM sleep disorders (5%), and cranial neuropathy (5%). Ten patients reported an inverse association between cough and ataxia severity. A very severe epidermal denervation was found in skin biopsies of all patients. Autonomic dysfunction comprised cardiovascular (67%), cardiovagal (54%), and/or sudomotor (50%) systems. Discussion: The presence of MN involvement, motor neuropathy, small fiber neuropathy, or extrapyramidal signs should not preclude RFC1 testing in cases of sensory neuronopathy. Indeed, the RFC1 spectrum can overlap not only with multiple system atrophy but also with hereditary motor and sensory neuropathy, hereditary sensory and autonomic neuropathy, and feeding dystonia phenotypes. Some clinical-paraclinical dissociations can pose diagnostic challenges, namely large and small fiber neuropathy and sudomotor dysfunction which are usually subclinical.

Comparison of inertial records during anticipatory postural adjustments obtained with devices of different masses.

Background: Step initiation involves anticipatory postural adjustments (APAs) that can be measured using inertial measurement units (IMUs) such as accelerometers. However, previous research has shown heterogeneity in terms of the population studied, sensors used, and methods employed. Validity against gold standard measurements was only found in some studies, and the weight of the sensors varied from 10 to 110 g. The weight of the device is a crucial factor to consider when assessing APAs, as APAs exhibit significantly lower magnitudes and are characterized by discrete oscillations in acceleration paths. Objective: This study aims to validate the performance of a commercially available ultra-light sensor weighing only 5.6 g compared to a 168-g smartphone for measuring APAs during step initiation, using a video capture kinematics system as the gold standard. The hypothesis is that APA oscillation measurements obtained with the ultra-light sensor will exhibit greater similarity to those acquired using video capture than those obtained using a smartphone. Materials and Methods: Twenty subjects were evaluated using a commercial lightweight MetaMotionC accelerometer, a smartphone and a system of cameras-kinematics with a reflective marker on lumbar vertebrae. The subjects initiated 10 trials of gait after a randomized command from the experimenter and APA variables were extracted: APAonset, APAamp, PEAKtime. A repeated measures ANOVA with post-hoc test analyzed the effect of device on APA measurements. Bland-Altman plots were used to evaluate agreement between MetaMotionC, smartphone, and kinematics measurements. Pearson's correlation coefficients were used to assess device correlation. Percentage error was calculated for each inertial sensor against kinematics. A paired Student's t-test compared th devices percentage error. Results: The study found no significant difference in temporal variables APAonset and PEAKtime between MetaMotionC, smartphone, and kinematic instruments, but a significant difference for variable APAamp, with MetaMotionC yielding smaller measurements. The MetaMotionC had a near-perfect correlation with kinematic data in APAonset and APAamp, while the smartphone had a very large correlation in APAamp and a near-perfect correlation in APAonset and PEAKtime. Bland-Altman plots showed non-significant bias between smartphone and kinematics for all variables, while there was a significant bias between MetaMotionC and kinematics for APAamp. The percentage of relative error was not significantly different between the smartphone and MetaMotionC. Conclusions: The temporal analysis can be assessed using ultralight sensors and smartphones, as MetaMotionC and smartphone-based measurements have been found to be valid compared to kinematics. However, caution should be exercised when using ultralight sensors for amplitude measurements, as additional research is necessary to determine their effectiveness in this regard.

Anticipatory postural adjustments in older versus young adults: a systematic review and meta-analysis.

BACKGROUND: Anticipatory postural adjustments (APAs) are a feedforward mechanism triggered in advance to a predictable perturbation, to help the individual counteract mechanical effects that the disturbance may cause. Whether or not this strategy is compromised in the elderly is not a consensus in the literature. METHODS: In this systematic review with meta-analysis, we investigated aging effects on postural control, based on anticipatory postural adjustments (APAs). We selected 11 eligible articles of the following databases: Lilacs, SciELO, PubMed, Cochrane Central, Embase, and CINAHL, involving 324 research participants, assessing their methodological quality and extracting electromyographic, posturographic, and kinematic measurements. We included studies that investigated the occurrence of APAs in healthy younger and older adults, published before 10th August 2022, in English. Studies involving participant with conditions that may affect balance or that did not report measures of onset or amplitude of electromyography (EMG), COP, or kinematics were excluded. To analyze the aggregated results from these studies, we performed the analysis based on the outcome measures (EMG, COP, or kinematic measures) used in individual studies. We calculated differences between younger and older adult groups as the mean differences between the groups and the estimated effect. Egger's test was conducted to evaluate whether this meta-analysis had publication bias. RESULTS: Through this review, older adults showed no significant difference in the velocity to perform a movement compared to the younger adults (MD 0.95, 95% CI -0.86, 2.76, I2 = 82%), but both muscle onset and center of pressure (COP) onset were significantly more delayed in older than in younger adults: erector spinae (MD -31.44, 95% CI -61.79, -1.09, I2 = 95%); rectus abdominis (RA) (MD -31.51, 95% CI -70.58, -3.57, I2 = 85%); tibialis anterior (TA) (MD -44.70, 95% CI -94.30, 4.91, I2 = 63%); soleus (SOL) (MD -37.74, 95% CI -65.43, -10.05, I2 = 91%); gastrocnemius (GAS) (MD -120.59, 95% CI -206.70, -34.49, I2 = 94%); quadriceps (Q) (MD -17.42, 95% CI -34.73, -0.12, I2 = 0%); biceps femoris (BF) (MD -117.47, 95% CI -192.55, -42.70, I2 = 97%); COP onset (MD -45.28, 95% CI -89.57, -0.98, I2 = 93%), and COP apa (COPapa) (MD 2.35, 95% CI -0.09, 4.79, I2 = 64%). These changes did not seem to be linked to the speed of movement but possibly to age-related physiological changes that indicated decreased motor control during APAs in older adults. CONCLUSIONS: Older adults use different postural strategies that aim to increase the safety margin and stabilize the body to perform the movement, according to the requirements imposed, and this should be considered in rehabilitation protocols. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD420119143198.

Wearable Inertial Sensor Approach for Postural Adjustment Assessments during Predictable Perturbations in Sport.

INTRODUCTION: Evidence supports the importance of efficient postural control to improve performance in sports. This involves the use of strategies such as anticipatory posture adjustments and compensatory adjustments. Technology makes analysis and assessments in sports cheaper, while being valid and reliable compared to the gold-standard assessment equipment. OBJECTIVES: This article aimed to test the validity and reliability of signals extracted from the sensor's accelerometer (Metamotion C), by comparing it to the data obtained from the gold-standard equipment (a three-dimensional video-motion-capture system). DESIGN: Observational, cross-sectional study. METHODS: We exposed 20 healthy young standing people to the pendulum impact paradigm, which consisted of predictable anteroposterior disturbances applied at the shoulder level. In order to measure this, we observed the acceleration of the center of mass in the anticipatory and compensatory phase of the disturbance and compared the signals of the two devices (Metamotion C and a motion-capture system). RESULTS: The validation results showed the significant linear correlation of all variables with a moderate to large correlation of r ≥ 0.5 between the devices. In contrast, the reliability results between sessions obtained by filming were all significant and above 0.75, indicating excellent reliability. The APAonset variable had a reasonable to high intra-class correlation in the anticipatory phase. In the compensatory phase, the CPAtime variable showed an excellent correlation. CONCLUSIONS: Metamotion C proved reasonably valid and highly reliable in measuring the center of mass acceleration compared to the camera system in both the anticipatory and compensatory phases.

Postural Adjustments in HTLV-1 Infected Patients during a Self-Initiated Perturbation.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) infection can be associated with tropical spastic paraparesis (TSP/HAM), which causes neurological myelopathy and sensory and muscle tone alterations, leading to gait and balance impairments. Once trunk perturbation is predicted, the motor control system uses anticipatory and compensatory mechanisms to maintain balance by recruiting postural muscles and displacement of the body's center of mass. METHODS: Twenty-six participants (control or infected) had lower limb muscle onset and center of pressure (COP) displacements assessed prior to perturbation and throughout the entire movement. RESULTS: Semitendinosus (ST) showed delayed onset in the infected group compared to the control group. The percentage of trials with detectable anticipatory postural adjustment was also lower in infected groups in the tibialis anterior and ST. In addition, COP displacement in the infected group was delayed, had a smaller amplitude, and took longer to reach the maximum displacement. CONCLUSIONS: HTLV-1 infected patients have less efficient anticipatory adjustments and greater difficulty recovering their postural control during the compensatory phase. Clinical assessment of this population should consider postural stability during rehabilitation programs.

A Challenging Case of Eyelid Ptosis and Diplopia Induced by Pembrolizumab.

We present the case of an 83-year-old female patient with gastric adenocarcinoma, who developed a subacute onset of eyelid ptosis and ophthalmoparesis, while being treated with pembrolizumab, raising the suspicion of myasthenia gravis. Workup exposed a broader systemic involvement, with liver, cardiac and skeletal muscle being affected as well. Further investigation lead us to change our initial diagnosis to multisystem inflammatory syndrome with isolated symptomatic ocular myositis, induced by pembrolizumab. High-dose steroids and immunoglobulin were started with a good outcome.

Postural Adjustments and Kinematic Index Finger Features in Frail Older Adults under Different Equilibrium Constraints.

Background: Anticipatory postural adjustments (APAs) are significantly affected by age and may represent restrictions on functional independence. Previous studies in young adults have already highlighted that changing postural stability (i.e., seated vs. upright posture) affects the motor planning and APAs. In frail older adults (FOAs), the effect of these different conditions of postural stability have not yet been established, and the present study aimed to disentangle this issue. Methods: Participants executed an arm-pointing task to reach a diode immediately after it turned on, under different conditions of stability (seated with and without foot support and in an upright posture). A kinematic profile of the index finger and postural electromyographic data were registered in their dominant-side leg muscles: tibialis anterior, soleus, rectus femoris, and semitendinosus. Results: The main finding of this study was that the adopted posture and body stabilization in FOAs did not reflect differences in APAs or kinematic features. In addition, they did not present an optimal APA, since postural muscles are recruited simultaneously with the deltoid. Conclusion: Thus, FOAs seem to use a single non-optimal motor plan to assist with task performance and counterbalance perturbation forces in which they present similar APAs and do not modify their kinematics features under different equilibrium constraints.

Gait patterns in ischemic and hemorrhagic post-stroke patients with delayed access to physiotherapy.

OBJECTIVES: (1) To assess the effects of a conventional, delayed physiotherapy protocol used by Ischemic Stroke (IS) and Hemorrhagic Stroke (HS) post-stroke patients, in their electromyographic activation patterns during hemiparetic gait; and (2) to study whether this protocol may improve the functional abilities in this population. METHODS: This is an observational, descriptive, and analytical quasi-experimental trial. Forty patients with unilateral IS ( n = 25 ) and HS ( n = 15 ) stroke were recruited; the stroke involved the motor cortex or sub-cortical areas, and the patients were able to walk independently. Interventions with standard protocols of physiotherapy were carried out. Evaluations (clinical and gait assessment) were performed at the time of admission and at the end of the protocol. Outcome measures include Stroke Impact Scale, Timed Up and Go Test, and gait electromyographic evaluation. RESULTS: Only IS patients (with an average of 124 . 4 ± 45 . 4 months delayed access to physiotherapy rehabilitation) had improvements in Timed Up and Go Test (change in speed =- 8 . 0 seg p < 0 . 05 ) and presented an anticipation of the onset in Upper leg muscles after the intervention. BF ( p = 0 . 05 ), ST ( p = 0 . 001 ), and RF ( p = 0 . 024 ), started their recruitment (onset) earlier at the swing phase of the gait cycle, which is more similar to the normal pattern (grey shadow). IS and HS ( 120 . 4 ± 28 . 4 months since last stroke) patients presented higher electromyographic activation, after physiotherapy, of the posterior leg muscles (gastrocnemius, semitendinosus and biceps femoris) during stance phase ( p < 0 . 05 ). CONCLUSION: IS patients had improvements after delayed conventional physiotherapy. For HS limited response to intervention was observed.

Chemoradiation induced multiple sclerosis-like demyelination.

We report the case of a 28-year-old man, diagnosed with a non-secreting, non-metastatic suprasellar germinoma treated with chemoradiation who developed, four months after completion of radiation therapy, multiple discrete demyelinating lesions mimicking multiple sclerosis (MS). The patient had no previous diagnosis of MS and the neuroimaging studies performed both at the time of diagnosis and after chemotherapy, pre-irradiation, showed no evidence of white matter lesions. He remained asymptomatic, with no focal neurological deficits. Biochemical analysis of the CSF was positive for the intrathecal synthesis of IgG with oligoclonal bands. Follow-up MRI six months later showed a spontaneous decrease in lesion size and resolution of associated inflammatory signs, with lesions remaining stable in number. We discuss the potential origin of these white matter lesions, which may correspond to MS-like late-delayed demyelination secondary to chemoradiation therapy, in a previously predisposed patient.

Postural adjustments impairments in elderly people with chronic low back pain.

Chronic low back pain (CLBP) is associated with postural control impairments and is highly prevalent in elderly people. The objective of this study is to verify whether anticipatory postural adjustments (APAs) and compensatory postural adjustments (CPAs) are affected by CLBP in elderly people by assessing their postural control during a self-initiated perturbation paradigm induced by rapid upper arm movement when pointing to a target. The participants' lower limb muscle onset and center of pressure (COP) displacements were assessed prior to perturbation and throughout the entire movement. T0 moment (i.e., the beginning of the movement) was defined as the anterior deltoid (DEL) onset, and all parameters were calculated with respect to it. The rectus femoris (RT), semitendinosus (ST), and soleous (SOL) showed delayed onset in the CLBP group compared with the control group: RF (control: - 0.094 ± 0.017 s; CLBP: - 0.026 ± 0.012 s, t = 12, p < 0.0001); ST (control: - 0.093 ± 0.013 s; CLBP: - 0.018 ± 0.019 s, t = 12, p < 0.0001); and SOL (control: - 0.086 ± 0.018 s; CLBP: - 0.029 ± 0.015 s, t = 8.98, p < 0.0001). In addition, COP displacement was delayed in the CLBP group (control: - 0.035 ± 0.021 s; CLBP: - 0.015 ± 0.009 s, t = 3; p = 0.003) and presented a smaller amplitude during APA COPAPA [control: 0.444 cm (0.187; 0.648); CLBP: 0.228 cm (0.096; 0.310), U = 53, p = 0.012]. The CLBP group required a longer time to reach the maximum displacement after the perturbation (control: 0.211 ± 0.047 s; CLBP 0.296 ± 0.078 s, t = 3.582, p = 0.0013). This indicates that CLBP elderly patients have impairments to recover their postural control and less efficient anticipatory adjustments during the compensatory phase. Our results suggest that people with CLBP have altered feedforward hip and ankle muscle control, as shown from the SOL, ST, and RT muscle onset. This study is the first study in the field of aging that investigates the postural adjustments of an elderly population with CLBP. Clinical assessment of this population should consider postural stability as part of a rehabilitation program.

Paroxysmal pain as the only presentation of focal epilepsy.

Painful seizures can be the only feature of focal epilepsy. Its localization on a limb favors the epileptic etiology, while abdominal or cephalic paroxysmal pain is not so specific. Painful somatosensory seizures arise from operculo-insular cortex.

Challenges of New Approaches in Metastatic Merkel Cell Carcinoma.

Merkel cell carcinoma is a rare and aggressive cutaneous tumor, and the use of checkpoint inhibitors immunotherapy is a recent indication in its metastatic setting, both first and second line. However, the widespread use of immunotherapy is associated with an increase of acute and late immune-mediated adverse events. We present a case of an elderly fit patient with metastatic Merkel cell carcinoma treated with pembrolizumab who developed diabetic ketoacidosis, a severe immune-mediated adverse event. A multidisciplinary approach was crucial to overcome the life-threatening event. Even with early treatment stop, the patient had a significant and durable response to the treatment for 15 months. Meanwhile, a progressive pan-cerebellar syndrome emerged, possible due to a paraneoplastic syndrome with a negative onco-neuronal antibody panel, although an autoimmune etiology associated with immunotherapy could not be excluded. Unfortunately, the situation was irreversible and refractory to immunomodulatory treatment. Despite the unpredictable toxicity, it is important to note the efficacy profile, with a progression-free survival of 15 months, which is higher than the one reported in reference clinical trials in this setting.

ATP1A3: an unusual antigen to consider in patients with subacute ataxia and vertical gaze palsy.

The anti-ATP1A3 antibody seems to be directed against a neuronal and cardiac surface protein of the proton ATPase. It was recently identified in a patient with a paraneoplastic syndrome characterized by cerebellar, neuro-ophthalmologic and other neurological symptoms. We report another patient with a similar clinical and radiological syndrome but with a different associated tumor and outcome.