Axon death signalling in Wallerian degeneration among species and in disease.

Axon loss is a shared feature of nervous systems being challenged in neurological disease, by chemotherapy or mechanical force. Axons take up the vast majority of the neuronal volume, thus numerous axonal intrinsic and glial extrinsic support mechanisms have evolved to promote lifelong axonal survival. Impaired support leads to axon degeneration, yet underlying intrinsic signalling cascades actively promoting the disassembly of axons remain poorly understood in any context, making the development to attenuate axon degeneration challenging. Wallerian degeneration serves as a simple model to study how axons undergo injury-induced axon degeneration (axon death). Severed axons actively execute their own destruction through an evolutionarily conserved axon death signalling cascade. This pathway is also activated in the absence of injury in diseased and challenged nervous systems. Gaining insights into mechanisms underlying axon death signalling could therefore help to define targets to block axon loss. Herein, we summarize features of axon death at the molecular and subcellular level. Recently identified and characterized mediators of axon death signalling are comprehensively discussed in detail, and commonalities and differences across species highlighted. We conclude with a summary of engaged axon death signalling in humans and animal models of neurological conditions. Thus, gaining mechanistic insights into axon death signalling broadens our understanding beyond a simple injury model. It harbours the potential to define targets for therapeutic intervention in a broad range of human axonopathies.

An assessment of the correlation between early postinfarction pyramidal tract Wallerian degeneration and nerve function recovery using diffusion tensor imaging.

This study aimed to evaluate the clinical significance of diffusion tensor imaging (DTI) in the early diagnosis of pyramidal tract Wallerian degeneration (WD) and assessment of neurological recovery following cerebral infarction. This study included 23 patients with acute cerebral infarction and 10 healthy adult controls. All participants underwent both magnetic resonance imaging (MRI) and DTI scans. DTI images were analyzed using the Functional MRI of the Brain Software Library to determine the regions of interest (ROI) and obtain the mean diffusivity (MD) and fractional anisotropy (FA) value for each ROI. The correlation between FA or MD and postinfarction functional recovery of the nervous system was further analyzed to assess the feasibility of using a DTI scan in the evaluation of functional recovery of the nervous system in patients with cerebral infarction. DTI may be useful in detecting signals of early postinfarction pyramidal tract WD and is useful for the evaluation of postinfarction neurological recovery. Cerebral lesions were detected using MRI in all patients. It was found that in some patients, the FA value of the ipsilateral pyramidal tract on DTI was decreased as early as day 3 after the onset of infarction and in all patients by day 7. Subsequent correlation studies showed that the FA value of the ipsilateral pyramidal tract on day 13 was negatively correlated with the National Institutes of Health Stroke Scale score, but positively correlated with the Barthel Index, motricity index, and modified Rankin Scale scores.

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.

Célula de Büngner / Büngner cell

Las lesiones del nervio periférico constituyen una condición clínica frecuente; por ello, entender su fisiopatología y los avances en el campo de la regeneración nerviosa es fundamental para brindar el mejor tratamiento a los pacientes. En los últimos años se ha venido dando cada vez mayor importancia a los eventos regenerativos después de la lesión, donde interviene en gran medida una expresión fenotípica única en este proceso, derivada de células ya presentes, fenómeno clave para la recuperación de la función del nervio lesionado. Este artículo revisó la literatura disponible con el objetivo de entender mejor este evento regenerativo y se encontraron procesos celulares y moleculares que suceden en los axones.

Peripheral nerve injuries are a common clinical condición for which the understanding of the pathophysiology and advances in the fteld of nerve regeneration are important to provide the best treatment for patients. In recent years, it has been giving increasing importance to the regenerative events after injury, where it operares largely unique phenotypic expression in this process, derived from cells already present, kev event for the recoven- of nerve function injured. A review of the literature is done with the aim of a better understanding of this regenerative event, fínding a series of cellular and molecular processes that go on axonal level.

Técnicas actuales de reparación nerviosa / Current techniques in peripheral nerve repair

Las lesiones del sistema nervioso periférico son uno de los retos terapéuticos de nuestra especialidad, no sólo por la dificultad técnica e instrumental necesaria para resolverlas, sino por la importancia de sus secuelas y los pobres resultados obtenidos con una deficiente técnica quirúrgica. Para obtener un óptimo resultado, es preceptivo, no sólo realizar un correcto diagnóstico, sino además, conocer y dominar las distintas opciones terapéuticas. El objetivo de la presente revisión es abordar las distintas indicaciones y técnicas quirúrgicas usadas actualmente para el tratamiento de las lesiones nerviosas

The injuries of the peripheral nervous system are one of the therapeutic challenges in our speciality given their technical and instrumental difficulty, the importance of the disability and the few results obtained with a deficient surgical technique. For an optimum result, a correct diagnosis is needed as well as to know and to dominate the different therapeutics options. The objetive of the current review is to deal with the different indications and surgery techniques currently used for the treatment of the nervous injuries

The use of compound muscle action potentials (CMAP) for postoperative monitoring of free functioning gracilis muscle transfer: A preliminary report.

BACKGROUND AND PURPOSES: The use of skin flap as a monitoring tool cannot sensitively reflect the vascularity of a functioning free muscle transfer (FFMT), and it may result in delayed detection of vascular compromise. We report the use of compound muscle action potentials (CMAPs) as a supplemental method in the monitoring of free gracilis transfers. SUBJECTS AND METHODS: In 46 successful free gracilis transfers in 23 patients following total brachial plexus injury (BPI), CMAPs were measured every hour for 75 h postoperatively. We analyzed the amplitude, latency, and duration to understand the Wallerian degeneration effect and thresholds to warn vascular compromise clinically. After the primary study, we applied CMAP monitoring for 23 clinical cases. MAIN FINDINGS: Three basic wave patterns of the CMAPs with or without dispersion were recognized. Forty-two CMAPs were successfully traced and 27 CMAPs with one constant wave pattern showed two types of amplitude and latency changes; positive and negative Wallerian degeneration. The mean 1-h maximal decreases of amplitudes and elongation of latency were 36% and 77%, respectively; however, they returned to the original pattern within 1 h. There were no significant differences of reinnervation time and final strength of elbow flexion between these 46 muscle transfers. In the clinical series, we experienced two cases of vascular compromise that showed CMAP critical alterations without skin flap changes. CONCLUSIONS: Our preliminary results show that the measurement of CMAPs has great potential for the sensitive and reliable monitoring of muscle circulation after FFMT. The clinical critical values of CMAP amplitude changes for vascular compromise are >40% sudden decrease, and they continued to decrease further. This technique is most useful for postoperative vascular monitoring of a buried muscle flap, and it is proven to be of clinical significance in current vascular compromised cases. LEVEL OF EVIDENCE: Level Ⅳ, Case Series.

[Anti-amphiphysin antibody-positive paraneoplastic neurological syndrome with a longitudinally extensive spinal cord lesion of the dorsal column].

A 53-year-old woman was admitted to our hospital because of gait disturbance and paresthesia of the lower extremities. She also had marked deep sense impairment in her lower limbs. Cervical MRI showed a longitudinally extensive spinal cord lesion of the dorsal column at levels C1-T11. The findings of cerebrospinal fluid examination, including the IgG index (0.65), were normal. Serum anti-AQP4 antibody was negative, but anti-amphiphysin antibody was positive. Electrophysiological examinations suggested the presence of lesions in the dorsal column of the spinal cord and dorsal root ganglion (DRG). Enlargement of and fluorodeoxyglucose accumulation in her left parasternal lymph node was observed on contrast-enhanced CT and PET-CT, respectively. The lymph node biopsy was underwent by using thoracoscopy. The metastasis of carcinoma was pathologically confirmed. Although the primary tumor was not detected on PET-CT re-examination, immunostaining of the biopsied lymph node specimen was positive for both the progesterone receptor and estrogen receptor. On the basis of these findings, the patient was diagnosed with paraneoplastic neurological syndrome due to potential breast cancer. The disorder is an immunological subacute sensory neuropathy with a longitudinally extensive spinal cord lesion of the dorsal column and a DRG lesion.

Clinical correlates of white matter tract degeneration in progressive supranuclear palsy.

OBJECTIVES: To use diffusion tensor imaging to assess white matter tract degeneration in progressive supranuclear palsy (PSP) and to investigate correlates between tract integrity and clinical measures. DESIGN: Case-control study. SETTING: Tertiary care medical center. PATIENTS/PARTICIPANTS: Twenty patients with probable PSP and 20 age- and sex-matched healthy controls were enrolled. All patients with PSP underwent standardized clinical testing, including the Frontal Behavioral Inventory and Frontal Assessment Battery to assess behavioral change, the PSP Rating Scale to measure disease severity, the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (parts II and III) to measure motor function, and the PSP Saccadic Impairment Scale to measure eye movement abnormalities. METHODS: Fractional anisotropy and mean diffusivity were measured using region of interest analysis and tract-based spatial statistics. RESULTS: Compared with controls, abnormal diffusivity was observed predominantly in the superior cerebellar peduncles, body of the corpus callosum, inferior longitudinal fasciculus, and superior longitudinal fasciculus in patients with PSP. Fractional anisotropy values in the superior cerebellar peduncles correlated with disease severity (r = -0.59, P = .006), inferior longitudinal fasciculus correlated with motor function (r = -0.51, P = .02), and superior longitudinal fasciculus correlated with severity of saccadic impairments (r = -0.45, P = .047). CONCLUSIONS: The results of this study demonstrate that PSP is associated with degeneration of the brainstem, association, and commissural fibers and that this degeneration likely plays an important role in clinical dysfunction.

Independent patterns of damage to retinocortical pathways in multiple sclerosis without a previous episode of optic neuritis.

Asymptomatic visual loss is a feature of multiple sclerosis (MS) but its relative impact on distinct retinocortical pathways is still unclear. The goal of this work was to investigate patterns of subclinical visual impairment in patients with MS with and without clinically associated previous optic neuritis (ON). We have used functional methods that assess parvo-, konio- and magnocellular pathways in order to compare pathophysiological mechanisms of damage in a population of 44 subjects with MS (87 eyes), with and without a previous episode of ON. These methods included chromatic contrast sensitivity across multiple chromatic axes (Cambridge Colour Test-parvo/konio pathways), perimetric achromatic contrast sensitivity for the magno pathway [frequency doubling technique (FDT)] and pattern visual evoked potentials (VEP). These measures were correlated with field sensitivity measures obtained using conventional automated static perimetry (ASP) and were also compared with conventional clinical chromatic/achromatic contrast sensitivity chart-based measures. We have found evidence for uncorrelated damage of all retinocortical pathways only in patients with MS without ON. VEP evidence for axonal damage was found in this group supporting the emerging notion of axonal damage even in sub-clinical stages of ON/MS pathophysiology. Only in this group was significant correlation of functional measures with disease stage observed, suggesting that distinct pathophysiological milestones are present before and after ON has occurred.

Imaging corticospinal degeneration in neonatal rats with unilateral cerebral infarction.

Recent human studies indicate that magnetic resonance (MR) imaging, particularly diffusion weighted imaging, detects abnormalities within the descending cortico-spinal tract following stroke. Whether these changes are directly related to processes of axonal degeneration and how MR changes (e.g. apparent diffusion coefficient of water (ADC) and T(2)) vary in their diagnostic utility over time is not known. The present study demonstrates that a commonly used rat model of neonatal transient unilateral hypoxia-ischemia provides similar diffusion weighted and ADC changes in the cerebral peduncle as those observed in human neonates clinically. Imaging the descending cortico-spinal tract in this model at defined acute (1-3 days) and chronic (1 and 4 weeks) time points demonstrates increased T(2) and progressive changes in ADC within the descending cortico-spinal tract in the first days to weeks following hypoxia-ischemia with a normalization by 1 week and further increases in ispilateral cerebral cortex by 4 weeks. These imaging changes are associated with reduced axonal neurofilament staining both at the subacute and more chronic time points. This demonstrates directly the utility of ADC and T(2) MRI to detect acute changes in axons associated with early Wallerian degeneration.

Motor unit number estimation in transected peripheral nerves.

OBJECTIVES: To study motor unit number estimation (MUNE) in acutely transected peripheral nerves, and to retest our previous observation which had revealed a discordance between the loss of compound muscle action potential (CMAP) size and decrease in MUNE during Wallerian degeneration. METHODS: In eight patients with nine transected median or ulnar nerves, a total of 18 electrophysiological studies were performed before the complete nerve degeneration ensues. CMAP recordings and incremental MUNE studies were performed by stimulation of the nerves at the wrist level and recording from the appropriate hand muscles. The same studies repeated on the contralateral side. RESULTS: Injury side to intact side ratios of the MUNEs were significantly higher than the CMAP ratios. Mean step areas in MUNE studies were found to be lower on the transected sides after 72 hours post-injury. DISCUSSION: These findings support the existence of an electrophysiologically observable asynchrony in neuromuscular synapse dysfunction during Wallerian degeneration.

Differential diagnosis of T2 hyperintense brainstem lesions: Part 2. Diffuse lesions.

Diffuse brainstem lesions are poorly defined, often large abnormalities and include tumors (gliomas and lymphomas) vasculitis (Behçet's disease), traumatic brainstem injury, degenerative disorders (Wallerian degeneration), infections, processes secondary to systemic conditions (central pontine myelinolysis, hypertensive or hepatic encephalopathy), and ischemic pathology (leukoaraiosis). Magnetic resonance imaging is the most appropriate imaging modality to use in evaluating lesions of this type, but often findings are nonspecific. Therefore, radiologists need to bear in mind such additional information as patient age and clinical features in making a differential diagnosis.

Magnetic resonance imaging demonstration of a single lesion causing Wallerian degeneration in ascending and descending tracts in the spinal cord.

A magnetic resonance image of a 50-year-old man with a remote history of cervical spine injury showed focal myelomalacia at C5 and hyperintense areas on T2-weighted images laterally and posteriorly in the cord above and below C5. We believe these lesions to be due to Wallerian degeneration, with the cephalocaudal level of the Wallerian degeneration lesions dependant on the direction of the tracts relative to the C5 lesion.

[Bilateral wallerian degeneration of the pontocerebellar fibers secondary to pontine stroke: a report of 4 cases]. / Degeneración walleriana bilateral de las fibras pontocerebelosas secundaria a ictus pontinos: presentación de 4 casos.

Wallerian degeneration occurs after demyelination of the distal neuronal axons due to proximal damage of any type. We present the magnetic resonance findings in four patients with brainstem stroke and signs of Wallerian degeneration in the pontocerebellar tracts. We reviewed the magnetic resonance studies in four patients with subacute or chronic stage pontine lesions and the signal alterations at the level of the medial cerebellar peduncles. We correlated the findings in T2-weighted sequences and diffusion-weighted sequences with the time of evolution and etiology of the stroke.

Pseudobloqueo de conducción en vasculitis aislada del sistema nervioso periférico / Pseudo-conduction block in nonsystemic vasculitic neuropath

Fundamento. La vasculitis aislada del sistema nerviosoperiférico (VASNP) afecta selectivamente a los vasanervorum, expresándose generalmente como una mononeuropatíamúltiple. Presentamos un caso de VASNPconfirmado histológicamente, destacando los hallazgosneurofisiológicos en fase aguda.Observación clínica. Mujer de 36 años con parestesiasy debilidad en mano derecha seguidas de paresia parala dorsiflexión del pie izquierdo. El primer estudio neurofisiológicomostraba amplitud reducida del potencialmotor del mediano derecho con estímulos proximales.Un segundo estudio mostraba signos de lesión axonalen varios nervios, incluyendo el mediano derecho.Conclusiones. La lesión isquémica aguda de un nerviopuede dar lugar a un patrón electroneurográfico debloqueo de conducción, como en el mediano derechodel caso descrito. Este fenómeno es conocido como“pseudobloqueo”, dado su carácter transitorio, conevolución a un patrón de neuropatía axonal. La sospechade VASNP requiere estudios neurofisiológicosseriados para una correcta tipificación de los patrones lesionales(AU)

Summary. Introduction. Nonsystemic vasculitic neuropathy(NSVN) is an inflammatory disorder of the vasanervorum which usually is expressed as a mononeuritismultiplex. We present a patient with NSVN with histologicalconfirmination focused on the neurophysiologicalfindings at the early stages.Case report. A 36 years-old woman presented with paresthesiaand weakness in her right hand followed byleft footdrop. The first neurophysiologic examinationshowed low amplitude of the right median nerve (RMN)CMAP with proximal stimulation. A second examinationshowed signs of axonal damage in several nerves, includingthe RMN.Conclusions. The acute ischemic damage of a nerve cangive a pattern of conduction block in the electroneurographicstudy as in the RMN of the presented case. Thisphenomenon is referred as “pseudo-conduction block”,since it is transient and evolves towards a definite patternof axonal neuropathy. When a vasculitic neuropathyis suspected, repeated neurophysiologic studiesare necessary in order to ensure a proper (appropriate)characterization of the lesional patterns(AU)