Neurographic course Of Wallerian degeneration after human peripheral nerve injury.

INTRODUCTION: Neurographic data on Wallerian degeneration (WD) after motor nerve injury are available only from animal studies and human case reports of 9 patients altogether. A precise knowledge of neurographic features of WD would be highly relevant for diagnostic, prognostic, therapeutic, and forensic aspects of traumatic lesions. METHODS: We prospectively studied WD in patients with a peripheral nerve injury. They underwent sequential neurographic examinations beginning no later than 3 days after the injury until a plateau of the amplitude of compound muscle action potential was reached. RESULTS: We examined 20 injured nerves from 16 patients. Four days after injury, all nerves showed amplitude decay to some extent, whereas 85% had reached their plateau at day 8. A length dependency of WD could be demonstrated. CONCLUSION: In humans, WD starts no later than day 4, shows length dependency, and is completed at day 8 in most nerves. Muscle Nerve 56: 247-252, 2017.

Safety and feasibility of long term administration of recombinant human granulocyte-colony stimulating factor in patients with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neuronal disease resulting in a loss of the upper and lower motor neurons and subsequent death within three to four years after diagnosis. Mouse models and preliminary human exposure data suggest that the treatment with granulocyte-colony stimulating factor (G-CSF) has neuro-protective effects and may delay ALS progression. As data on long-term administration of G-CSF in patients with normal bone marrow (BM) function are scarce, we initiated a compassionate use program including 6 ALS patients with monthly G-CSF treatment cycles. Here we demonstrate that G-CSF injection was safe and feasible throughout our observation period up to three years. Significant decrease of mobilization efficiency occurred in one patient and a loss of immature erythroid progenitors was observed in all six patients. These data imply that follow-up studies analyzing BM function during long-term G-CSF stimulation are required.

Entrapment syndrome of multiple nerves in graft-versus-host disease.

INTRODUCTION: Peripheral nerve entrapment syndromes are associated with hereditary neuropathy with liability to pressure palsies and a variety of rheumatic and endocrinological diseases. METHODS: We report a patient with entrapment syndromes of multiple nerves associated with chronic graft-versus-host-disease (GVHD) after allogeneic hematopoietic stem cell transplantation. Nerve ultrasound, histology, and ultrastructural changes were assessed. RESULTS: The 51-year-old man had developed severe deep dermal sclerosis due to chronic GVHD with a progressive polyneuropathy and entrapment syndromes of multiple nerves. Pre-stenotic enlargement was shown by nerve ultrasound. Histology demonstrated fibrosis of the epineurium with scarce infiltration of macrophages. Electron microscopy demonstrated alterations of the myelin sheaths and marked depletion of normal-sized myelinated nerve fibers. CONCLUSIONS: In addition to polyneuropathy, chronic GVHD can be associated with peripheral nerve entrapment syndromes and should be added to the differential diagnosis of compressive neuropathies.

Lower Motoneuron Dysfunction Impacts Spontaneous Motor Recovery in Acute Cervical Spinal Cord Injury.

Paresis after spinal cord injury (SCI) is caused by damage to upper and lower motoneurons (LMNs) and may differentially impact neurological recovery. This prospective monocentric longitudinal observational study investigated the extent and severity of LMN dysfunction and its impact on upper extremity motor recovery after acute cervical SCI. Pathological spontaneous activity at rest and/or increased discharge rates of motor unit action potentials recorded by needle electromyography (EMG) were taken as parameters for LMN dysfunction and its relation to the extent of myelopathy in the first available spine magnetic resonance imaging (MRI) was determined. Motor recovery was assessed by standardized neurological examination within the first four weeks (acute stage) and up to one year (chronic stage) after injury. Eighty-five muscles of 17 individuals with cervical SCI (neurological level of injury from C1 to C7) and a median age of 54 (28-59) years were examined. The results showed that muscles with signs of LMN dysfunction peaked at the lesion center (Χ2 [2, n = 85] = 6.6, p = 0.04) and that the severity of LMN dysfunction correlated with T2-weighted hyperintense MRI signal changes in routine spine MRI at the lesion site (Spearman ρ = 0.31, p = 0.01). Muscles exhibiting signs of LMN dysfunction, as indicated by pathological spontaneous activity at rest and/or increased discharge rates of motor unit action potentials, were associated with more severe paresis in both the acute and chronic stages after SCI (Spearman ρ acute = -0.22, p = 0.04 and chronic = -0.31, p = 0.004). Moreover, the severity of LMN dysfunction in the acute stage was also associated with a greater degree of paresis (Spearman ρ acute = -0.24, p = 0.03 and chronic = -0.35, p = 0.001). While both muscles with and without signs of LMN dysfunction were capable of regaining strength over time, those without LMN dysfunctions had a higher potential to reach full strength. Muscles with signs of LMN dysfunction in the acute stage displayed increased amplitudes of motor unit action potentials with chronic-stage needle EMG, indicating reinnervation through peripheral collateral sprouting as compensatory mechanism (Χ2 [1, n = 72] = 4.3, p = 0.04). Thus, LMN dysfunction represents a relevant factor contributing to motor impairment and recovery in acute cervical SCI. Defined recovery mechanisms (peripheral reinnervation) may at least partially underlie spontaneous recovery in respective muscles. Therefore, assessment of LMN dysfunction could help refine prediction of motor recovery after SCI.

Discharge rates in electromyography distinguish early between peripheral and central paresis.

INTRODUCTION: Abnormally increased discharge rates (DRs) of motor unit potentials on concentric needle electromyography (CNEMG) indicate a loss of motor units in peripheral neurogenic lesions. METHODS: To determine when increased DRs occur during the course of a peripheral nerve lesion, we retrospectively analyzed CNEMG recordings of 19 patients with acute weakness of peripheral origin. RESULTS: The initial CNEMG studies took place from 3.7 hours to 10 days after the onset of the lesion. Abnormally increased DRs (≥20/s) were found in all but 1 of the muscles in which MRC grade was <4. Peripheral neurogenic damage was confirmed in all patients thereafter. The DRs depended on neither the kind of lesion nor the time between onset and CNEMG examination. CONCLUSIONS: The measurement of DRs of motor unit potentials is helpful immediately after a sudden paresis of MRC grade 3 or worse to differentiate between a central and a peripheral lesion.

Chance or challenge, spoilt for choice? New recommendations on diagnostic and therapeutic considerations in hereditary transthyretin amyloidosis with polyneuropathy: the German/Austrian position and review of the literature.

Hereditary transthyretin amyloidosis is caused by pathogenic variants (ATTRv) in the TTR gene. Alongside cardiac dysfunction, the disease typically manifests with a severely progressive sensorimotor and autonomic polyneuropathy. Three different drugs, tafamidis, patisiran, and inotersen, are approved in several countries, including the European Union and the United States of America. By stabilizing the TTR protein or degrading its mRNA, all types of treatment aim at preventing amyloid deposition and stopping the otherwise fatal course. Therefore, it is of utmost importance to recognize both onset and progression of neuropathy as early as possible. To establish recommendations for diagnostic and therapeutic procedures in the follow-up of both pre-symptomatic mutation carriers and patients with manifest ATTRv amyloidosis with polyneuropathy, German and Austrian experts elaborated a harmonized position. This paper is further based on a systematic review of the literature. Potential challenges in the early recognition of disease onset and progression are the clinical heterogeneity and the subjectivity of sensory and autonomic symptoms. Progression cannot be defined by a single test or score alone but has to be evaluated considering various disease aspects and their dynamics over time. The first-line therapy should be chosen based on individual symptom constellations and contra-indications. If symptoms worsen, this should promptly implicate to consider optimizing treatment. Due to the rareness and variability of ATTRv amyloidosis, the clinical course is most importantly directive in doubtful cases. Therefore, a systematic follow-up at an experienced center is crucial to identify progression and reassure patients and carriers.

Modeling and Bioinformatics Identify Responders to G-CSF in Patients With Amyotrophic Lateral Sclerosis.

Objective: Developing an integrative approach to early treatment response classification using survival modeling and bioinformatics with various biomarkers for early assessment of filgrastim (granulocyte colony stimulating factor) treatment effects in amyotrophic lateral sclerosis (ALS) patients. Filgrastim, a hematopoietic growth factor with excellent safety, routinely applied in oncology and stem cell mobilization, had shown preliminary efficacy in ALS. Methods: We conducted individualized long-term filgrastim treatment in 36 ALS patients. The PRO-ACT database, with outcome data from 23 international clinical ALS trials, served as historical control and mathematical reference for survival modeling. Imaging data as well as cytokine and cellular data from stem cell analysis were processed as biomarkers in a non-linear principal component analysis (NLPCA) to identify individual response. Results: Cox proportional hazard and matched-pair analyses revealed a significant survival benefit for filgrastim-treated patients over PRO-ACT comparators. We generated a model for survival estimation based on patients in the PRO-ACT database and then applied the model to filgrastim-treated patients. Model-identified filgrastim responders displayed less functional decline and impressively longer survival than non-responders. Multimodal biomarkers were then analyzed by PCA in the context of model-defined treatment response, allowing identification of subsequent treatment response as early as within 3 months of therapy. Strong treatment response with a median survival of 3.8 years after start of therapy was associated with younger age, increased hematopoietic stem cell mobilization, less aggressive inflammatory cytokine plasma profiles, and preserved pattern of fractional anisotropy as determined by magnetic resonance diffusion tensor imaging (DTI-MRI). Conclusion: Long-term filgrastim is safe, is well-tolerated, and has significant positive effects on disease progression and survival in a small cohort of ALS patients. Developing and applying a model-based biomarker response classification allows use of multimodal biomarker patterns in full potential. This can identify strong individual treatment responders (here: filgrastim) at a very early stage of therapy and may pave the way to an effective individualized treatment option.

The Prevention of Positioning Injuries During Gynecologic Surgery. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/077, October 2020).

Purpose Positioning injuries are relatively common, forensically highly relevant complications of gynecologic surgery. The aim of this official AWMF S2k-guideline is to provide statements and recommendations on how to prevent positioning injuries using the currently available literature. The literature was evaluated by an interdisciplinary group of experts from professional medical societies. The consensus on recommendations and statements was achieved in a structured consensus process. Method The current guideline is based on the expired S1-guideline, which was updated by a systematic search of the literature and a review of relevant publications issued between February 2014 and March 2019. Statements were compiled and voted on by a panel of experts. Recommendations The guideline provides general and specific recommendations on the prevention, diagnosis and treatment of positioning injuries.

Magnetic Measurement of Electrically Evoked Muscle Responses With Optically Pumped Magnetometers.

OBJECTIVE: Electroneurography has been an essential method for assessing peripheral nerve disorders for decades. During this procedure, a nerve is briefly electrically excited, and nerve conduction properties are identified by indirect means from the behavior of the innervated muscle. The magnetic field of the resulting muscle response can also be recorded by novel, uncooled magnetometers, which have become very attractive for different medical applications over recent years. These highly sensitive magnetometers are called optically pumped magnetometers. METHODS: We performed unaveraged and averaged magnetic signal detection of electrically evoked muscle responses using optically pumped magnetometers. We then discussed the suitability of this procedure for clinical applications in the context of diagnostic value and in direct comparison with the current electrical gold standard. RESULTS: The magnetic detection of muscle responses is possible using optically pumped magnetometers. Our magnetic results (averaged and unaveraged) closely match those from electrical measurements. CONCLUSION: Optically pumped magnetometers provide an alternative, contactless technology for electrode-based motor studies, but they are currently not ready for routine clinical use. This costly technology requires additional earth magnetic shielding because this is a prerequisite for proper operation. Currently, there are no diagnostic advantages over electrical measurements. Additionally, the required measurement setup and procedure are much more complicated. SIGNIFICANCE: In contrast to already published proof-of-principle studies for magnetomyography, we report in detail the results of the magnetic measurements of electrically evoked muscle responses in a shielded environment by applying supramaximal stimulation and finally validate our findings with electroneurography data as a reference.

Signal Modeling and Simulation of Temporal Dispersion and Conduction Block in Motor Nerves.

OBJECTIVE: Electroneurography is a well-established diagnostic test for supporting the diagnosis of disorders of myelinated peripheral nerves. Neurophysiological quantities are automatically calculated and are used to determine the pathology of the nerve (axonal damage) or its sheath (myelin damage). Specific differential diagnostic criteria are derived from time-domain normative data, which result primarily from a computer simulation in the early 1990s based on animal data, namely rats. However, the rat signals studied differ significantly from those of humans because of anatomical differences. METHODS: We present a model-based simulation of nerve conduction in healthy and pathological motor nerves. In contrast to earlier simulations, the present model is based on motor unit action potentials extracted from real human measurements facilitating the generation of realistic signals, starting from a conduction velocity distribution. In addition to the modeling of healthy nerves, we model a hereditary peripheral nerve disease as well as an acute and a chronic inflammatory demyelinating condition. RESULTS: Quantitative signal differences based on standard variables in the time-domain are presented. The findings for the demyelinating conditions demonstrate amplitude reductions of 71% and 65% between the distal and proximal responses, which result from an increase in the variance of the nerve fiber conduction velocities. CONCLUSION: The simulation results closely match those of empirical measurements, indicating that the signal model captures relevant pathological mechanisms. An amplitude reduction of more than 50% in demyelinating conditions is in accordance with routine measurements and shows that temporal dispersion is quite well-modeled compared to previous simulation models. SIGNIFICANCE: The simulation outcomes can serve as the basis for an improved pathophysiological understanding of peripheral nerve disorders and should aid neurophysiologists to refine their diagnostic armamentarium resulting in a more precise differential diagnosis.

Use of botulinum toxin A in adult neurological disorders: efficacy, tolerability and safety.

The protein botulinum neurotoxin A (BoNT/A) is one of seven distinct neurotoxins produced by Clostridium botulinum. BoNT/A blocks cholinergic synapses with an extremely high specificity and potency. Appropriately purified and diluted, BoNT/A serves as a reliable and well tolerated drug that is applied by local injection.The efficacy of BoNT/A is evident in the symptomatic therapy of disorders in which muscular hyperactivity plays a prominent role, such as focal dystonias and hemifacial spasm; in these disorders, BoNT/A is considered first-line therapy. BoNT/A is also beneficial in the treatment of both adults and children with spasticity of various causes. The pain that frequently accompanies these conditions is effectively reduced by BoNT/A. A genuine analgesic effect for BoNT/A unrelated to skeletal muscle spasmolysis has been suggested on the basis of in vitro and in vivo (animal) data. However, studies in humans designed to detect such an effect were negative, as were controlled studies of BoNT/A in patients with primary headache disorders.BoNT/A also acts on cholinergic synapses of the autonomic nervous system, and injection of BoNT/A into salivary glands significantly decreases the production of saliva. This may be beneficial for patients with Parkinson's disease, in whom the excessive production of saliva may be problematic.Overall, BoNT/A has been confirmed as an efficacious, predictable and well tolerated drug in an ever-increasing number of neurological disorders.

Combinatory Biomarker Use of Cortical Thickness, MUNIX, and ALSFRS-R at Baseline and in Longitudinal Courses of Individual Patients With Amyotrophic Lateral Sclerosis.

Objective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative process affecting upper and lower motor neurons as well as non-motor systems. In this study, precentral and postcentral cortical thinning detected by structural magnetic resonance imaging (MRI) were combined with clinical (ALS-specific functional rating scale revised, ALSFRS-R) and neurophysiological (motor unit number index, MUNIX) biomarkers in both cross-sectional and longitudinal analyses. Methods: The unicenter sample included 20 limb-onset classical ALS patients compared to 30 age-related healthy controls. ALS patients were treated with standard Riluzole and additional long-term G-CSF (Filgrastim) on a named patient basis after written informed consent. Combinatory biomarker use included cortical thickness of atlas-based dorsal and ventral subdivisions of the precentral and postcentral cortex, ALSFRS-R, and MUNIX for the musculus abductor digiti minimi (ADM) bilaterally. Individual cross-sectional analysis investigated individual cortical thinning in ALS patients compared to age-related healthy controls in the context of state of disease at initial MRI scan. Beyond correlation analysis of biomarkers at cross-sectional group level (n = 20), longitudinal monitoring in a subset of slow progressive ALS patients (n = 4) explored within-subject temporal dynamics of repeatedly assessed biomarkers in time courses over at least 18 months. Results: Cross-sectional analysis demonstrated individually variable states of cortical thinning, which was most pronounced in the ventral section of the precentral cortex. Correlations of ALSFRS-R with cortical thickness and MUNIX were detected. Individual longitudinal biomarker monitoring in four slow progressive ALS patients revealed evident differences in individual disease courses and temporal dynamics of the biomarkers. Conclusion: A combinatory use of structural MRI, neurophysiological and clinical biomarkers allows for an appropriate and detailed assessment of clinical state and course of disease of ALS.

Biomarker Supervised G-CSF (Filgrastim) Response in ALS Patients.

Objective: To evaluate safety, tolerability and feasibility of long-term treatment with Granulocyte-colony stimulating factor (G-CSF), a well-known hematopoietic stem cell factor, guided by assessment of mobilized bone marrow derived stem cells and cytokines in the serum of patients with amyotrophic lateral sclerosis (ALS) treated on a named patient basis. Methods: 36 ALS patients were treated with subcutaneous injections of G-CSF on a named patient basis and in an outpatient setting. Drug was dosed by individual application schemes (mean 464 Mio IU/month, range 90-2160 Mio IU/month) over a median of 13.7 months (range from 2.7 to 73.8 months). Safety, tolerability, survival and change in ALSFRS-R were observed. Hematopoietic stem cells were monitored by flow cytometry analysis of circulating CD34+ and CD34+CD38- cells, and peripheral cytokines were assessed by electrochemoluminescence throughout the intervention period. Analysis of immunological and hematological markers was conducted. Results: Long term and individually adapted treatment with G-CSF was well tolerated and safe. G-CSF led to a significant mobilization of hematopoietic stem cells into the peripheral blood. Higher mobilization capacity was associated with prolonged survival. Initial levels of serum cytokines, such as MDC, TNF-beta, IL-7, IL-16, and Tie-2 were significantly associated with survival. Continued application of G-CSF led to persistent alterations in serum cytokines and ongoing measurements revealed the multifaceted effects of G-CSF. Conclusions: G-CSF treatment is feasible and safe for ALS patients. It may exert its beneficial effects through neuroprotective and -regenerative activities, mobilization of hematopoietic stem cells and regulation of pro- and anti-inflammatory cytokines as well as angiogenic factors. These cytokines may serve as prognostic markers when measured at the time of diagnosis. Hematopoietic stem cell numbers and cytokine levels are altered by ongoing G-CSF application and may potentially serve as treatment biomarkers for early monitoring of G-CSF treatment efficacy in ALS in future clinical trials.

Botulinum toxin A does not alter capsaicin-induced pain perception in human skin.

A genuine peripheral antinociceptive and anti-inflammatory effect of Botulinum neurotoxin type A (BoNT/A) has been proposed but could not be demonstrated in humans so far. Therefore, 100 mouse units of Botulinum toxin A (Dysport) and placebo were injected in a double blind paradigm in defined skin areas of 50 subjects. At baseline and after 4 and 8 weeks allodynia was induced in the skin areas with capsaicin ointment. Heat and cold pain threshold temperatures were measured with quantitative sensory testing, and threshold intensities upon electrical stimulation with a pain specific surface electrode were determined. No BoNT/A related differences in pain perception were found at any quality. There is neither a direct peripheral antinociceptive effect nor a significant effect against neurogenic inflammation of BoNT/A in humans.

Misleading bilateral blink reflex loss in a severe tetanus case.

Tetanus is rare and often forgotten in the diagnostic workup. The diagnosis is mainly based on typical clinical symptoms, because of missing sensitive paraclinical test. As described in our case, a missing bilateral blink reflex may occur in severe tetanus, which should not lead to the rejection of the diagnosis.

Thin corpus callosum and amyotrophy in spastic paraplegia--case report and review of literature.

We report the clinical, structural, functional and genetic characterization of a 37-year-old Caucasian female, presenting as a sporadic case of complicated spastic paraplegia with thin corpus callosum (CC), cognitive impairment, amyotrophy of the hand muscles and a sensorimotor neuropathy and review the literature for spastic paraplegia with thin CC. Magnetic resonance imaging (MRI) examination revealed a thin CC with fronto-parietal cortical atrophy. 18Fluordesoxyglucose positron emission tomography (FDG-PET) showed reduced cortical and thalamic metabolism. By transcranial magnetic stimulation, we delineated a severe impairment of transcallosal inhibition. Sequence analysis did not reveal disease causing mutations in the genes SLC12A6 (Andermann), Spastin (SPG 4), BSCL2 (SPG 17) and Spartin (SPG 20). We reviewed the literature for HSP with thin CC and found 113 HSP patients with thin CC previously described (35 with linkage to chromosome 15q13-15). Thin CC and peripheral neuropathy often appear together in spastic paraplegia and might be indicative for combined degeneration mechanism of central and peripheral axons.

Stein's Double Cross-Lip Flaps Combined with Johanson's Step Technique for Subtotal Lower Lip Reconstruction.

UNLABELLED: In a previous study, a single cross-lip flap (Abbe flap) combined with Johanson's step technique for repair of defects of more than 2/3 of the lower lip was superior, in terms of aesthetic and functional outcome, compared with Bernard Webster-related techniques (cheek advancement). Herewith, a double cross-lip flap (Stein procedure) is proposed for repair of subtotal lower lip defects. A systematic review of the Stein procedure is provided. METHODS: Two patients underwent a paramedian double cross-lip flap, preserving the aesthetic subunit philtrum column combined with the Johanson's step technique. The aesthetic and functional outcomes and the surgical steps are demonstrated in the videos. An electromyographic study was performed 6 months and 4 years after surgery. A PubMed and a Google Scholar search were performed for the Stein procedure published in 1848. RESULTS: Lip competence was achieved directly after sectioning of the cross-lip pedicles in both patients. Lips progressivity expanded in the first 6 months. No microstomia was observed. Electromyography showed successful reinnervation of the transplanted muscles at 6 months. Four years after surgery, the electromyographic findings were consolidated. Since 1975, 7 articles on the double cross-lip procedure have been published: 4 in English, 1 in French, and 2 in Japanese. None of those articles reported on any supplemental lower lip advancement or on any electromyographic study. CONCLUSIONS: The rationale of using 2 cross-lip flaps and a lip-cheek advancement according to Johanson seems to achieve functionally and aesthetically superior results compared with other techniques described for subtotal lower lip reconstruction.

Toward the validation of a new method (MUNIX) for motor unit number assessment.

INTRODUCTION: This prospectively designed study analyzed the correlation of a new, non-invasive neurophysiological method (Motor Unit Number Index - MUNIX) with two established Motor Unit Number Estimation (MUNE) methods. METHODS: MUNIX and incremental stimulation MUNE (IS-MUNE) were done in the abductor digiti minimi muscle (ADM), while MUNIX and spike-triggered averaging MUNE (STA-MUNE) were tested in the trapezius muscle. Twenty healthy subjects and 17 patients with amyotrophic lateral sclerosis (ALS) were examined. RESULTS: MUNIX and MUNE values correlated significantly (ADM: n=108; Spearman-Rho; r=0.88; p<0.01; trapezius muscle: n=49; Spearman-Rho; r=0.46; p<0.01). DISCUSSION: MUNIX indeed reflects the number of motor units in a muscle, and may sensibly be recorded from the trapezius muscle. With MUNIX being both much more patient friendly and much more rapid to assess than MUNE, the results support the use of MUNIX when motor unit number assessment is desired.

Autonomic and peripheral nervous system function in acute tick-borne encephalitis.

OBJECTIVES: Tick-borne encephalitis (TBE) is an emerging flaviviral zoonosis in Central and Eastern Europe. TBE can present as meningitis, meningoencephalitis, or meningoencephalomyelitis. Dysfunction of the autonomic (ANS) and peripheral motoric and sensory nervous system (PNS) might contribute to acute and long-term complications. We aimed to examine, whether the ANS and PNS are affected in acute TBE. METHODS: Fourteen patients with acute TBE, 17 with diabetic polyneuropathy (d-PNP), and 30 healthy controls (HC) were examined in our single-center, prospective study. ANS and PNS function was assessed by time- and frequency-domain parameters of the heart rate (HR) variability at rest and deep respiration, and by sural and tibial nerve neurography. Primary endpoint was the HR variability at rest measured by root mean square of the successive differences (RMSSD). Autonomic symptoms and quality of life (QoL) were assessed by questionnaires. RESULTS: Tick-borne encephalitis patients had a lower RMSSD at rest (TBE 13.1 ± 7.0, HC 72.7 ± 48.3; P < 0.001) and deep respiration (TBE 42.8 ± 27.0, HC 109.7 ± 68.8; P < 0.01), an increased low-frequency to high-frequency power component ratio at rest (TBE 4.0 ± 4.0, HC 0.8 ± 0.5; P < 0.001), and a higher minimal heart rate at rest (TBE 85.4 ± 7.0, HC 69.5 ± 8.5; P < 0.001), all similar to patients with d-PNP, indicating sympathovagal imbalance with increased sympathetic activation. Compared to HC, sural and tibial nerve conduction velocities and action potential amplitudes were reduced, ANS symptoms were more frequent, and QoL was lower in patients with TBE. CONCLUSIONS: The ANS and to a lesser degree the PNS are affected by acute TBE, which could potentially contribute to short- and long-term morbidity.