[Hereditary transthyretin amyloidosis: A multifaceted disease]. / Die hereditäre Transthyretin-Amyloidose - eine facettenreiche Erkrankung.

Hereditary transthyretin amyloidosis (ATTRv, amyloidosis transthyretin variant) encompasses a broad spectrum of clinical manifestations, with polyneuropathy and cardiomyopathy being the most common organ manifestations. In addition, other organ systems such as kidneys, gastrointestinal tract, eyes and brain may be affected. If left untreated, the disease progresses rapidly, leading to significantly reduced quality of life and increased mortality. Early diagnosis is of particular importance, as drug treatment options have been available for a few years.

Ultrasound of the Biceps Muscle in Idiopathic Parkinson's Disease with Deep Brain Stimulation: Rigidity Can Be Quantified by Shear Wave Elastography.

Rigidity in Parkinson's disease (PD) is assessed by clinical scales, mostly the Unified Parkinson's Disease Rating Scale of the Movement Disorders Society (MDS-UPDRS). While the MDS-UPDRS-III ranges on an integer from 0 to 4, we investigated whether muscle ultrasound shear wave elastography (SWE) offers a refined assessment. Ten PD patients (five treated with deep brain stimulation (DBS) and levodopa, five with levodopa only) and ten healthy controls were included. Over a period of 80 min, both the SWE value and the item 22b-c of the MDS-UPDRS-III were measured at 5 min intervals. The measurements were performed bilaterally at the biceps brachii muscle (BB) and flexor digitorum profundus muscle in flexion and passive extension. Rigidity was modified and tracked under various therapeutic conditions (with and without medication/DBS). The feasibility of SWE for objective quantification was evaluated by correlation with the UPDRS-III: considering all positions and muscles, there was already a weak correlation (r = 0.01, p < 0.001)­in a targeted analysis, the BB in passive extension showed a markedly higher correlation (r = 0.494, p < 0.001). The application of dopaminergic medication and DBS resulted in statistically significant short-term changes in both clinical rigidity and SWE measurements in the BB (p < 0.001). We conclude that rigidity is reflected in the SWE measurements, indicating that SWE is a potential non-invasive quantitative assessment tool for PD.

Optically pumped magnetometers detect altered maximal muscle activity in neuromuscular disease.

Optically pumped magnetometers (OPM) are quantum sensors that enable the contactless, non-invasive measurement of biomagnetic muscle signals, i.e., magnetomyography (MMG). Due to the contactless recording, OPM-MMG might be preferable to standard electromyography (EMG) for patients with neuromuscular diseases, particularly when repetitive recordings for diagnostic and therapeutic monitoring are mandatory. OPM-MMG studies have focused on recording physiological muscle activity in healthy individuals, whereas research on neuromuscular patients with pathological altered muscle activity is non-existent. Here, we report a proof-of-principle study on the application of OPM-MMG in patients with neuromuscular diseases. Specifically, we compare the muscular activity during maximal isometric contraction of the left rectus femoris muscle in three neuromuscular patients with severe (Transthyretin Amyloidosis in combination with Pompe's disease), mild (Charcot-Marie-Tooth disease, type 2), and without neurogenic, but myogenic, damage (Myotonia Congenita). Seven healthy young participants served as the control group. As expected, and confirmed by using simultaneous surface electromyography (sEMG), a time-series analysis revealed a dispersed interference pattern during maximal contraction with high amplitudes. Furthermore, both patients with neurogenic damage (ATTR and CMT2) showed a reduced variability of the MMG signal, quantified as the signal standard deviation of the main component of the frequency spectrum, highlighting the reduced possibility of motor unit recruitment due to the loss of motor neurons. Our results show that recording pathologically altered voluntary muscle activity with OPM-MMG is possible, paving the way for the potential use of OPM-MMG in larger studies to explore the potential benefits in clinical neurophysiology.

People With Parkinson's Disease and Freezing of Gait Show Abnormal Low Frequency Activity of Antagonistic Leg Muscles.

OBJECTIVE: Freezing of gait is detrimental to patients with idiopathic Parkinson's disease (PD). Its pathophysiology represents a multilevel failure of motor processing in the cortical, subcortical, and brainstem circuits, ultimately resulting in ineffective motor output of the spinal pattern generator. Electrophysiological studies pointed to abnormalities of oscillatory activity in freezers that covered a broad frequency range including the theta, alpha, and beta bands. We explored muscular frequency domain activity with respect to freezing, and used deep brain stimulation to modulate these rhythms thereby evaluating the supraspinal contributions to spinal motor neuron activity. METHODS: We analyzed 9 PD freezers and 16 healthy controls (HC). We studied the patients after overnight withdrawal of dopaminergic medication with stimulation off, stimulation of the subthalamic nucleus (STN-DBSonly) or the substantia nigra pars reticulate (SNr-DBSonly), respectively. Patients performed a walking paradigm passing a narrow obstacle. We analyzed the frequency-domain spectra of the tibialis anterior (TA) and gastrocnemius (GA) muscles in 'regular gait' and during the 'freezing' episodes. RESULTS: In stimulation off, PD freezers showed increased muscle activity of the alpha and low-beta band compared to HC in both TA and GA. This activity increase was present during straight walking and during the freezes to similar extent. STN- but not SNr-DBS decreased this activity and paralleled the clinical improvement of freezing. CONCLUSION: We found increased muscle activation of the alpha and lower beta band in PD freezers compared to HC, and this was attenuated with STN-DBS. Future studies may use combined recordings of local field potentials, electroencephalography (EEG), and electromyography (EMG) to interrogate the supraspinal circuit mechanisms of the pathological activation pattern of the spinal pattern generator.