Axonal Lesions Research Articles

A Morphological Study of HLA-DR-Immunopositive Cells in Multiple Sclerosis Lesions and Their Implications for Pathogenesis

Background: Multiple sclerosis (MS) is characterized by white matter demyelinating plaques, which can be classified as active, chronic active, or chronic inactive based on the extent of demyelination, cellularity, and inflammation. Microglia and macrophages play a central role in these processes. This study aimed to investigate the morphological characteristics of HLA-DR-immunopositive cells in these plaques to improve our understanding of the roles of these cells in MS plaques. Methods: This study is a retrospective post-mortem histopathological study. We analyzed 90 plaques from 6 MS cases. Of the plaques studied, 77 were grouped into three categories: 28 active, 34 chronic active, and 15 chronic inactive. Additionally, five vacuolated white matter lesions, two axonal degeneration lesions, and six lesions with mixed histological features were included. Six control cases were also examined to assess HLA-DR-immunopositive cell expression across various age groups. The cells were classified based on their morphology into two types: round cells without processes (macrophages) and cells with varying processes and shapes (ramified microglia). Results: Both macrophages and ramified microglia were present in all lesion types, with a focus on identifying the predominant cell type. Of the 28 active plaques, macrophages were the primary cell type in 25 plaques, while ramified microglia predominated in 3. In the center of 49 chronic plaques, scattered ramified microglia were observed in 46, with three plaques showing a predominance of macrophages. Among the 34 chronic active lesions, ramified microglia were the main cell type in the periphery of 32 plaques, with the remaining two predominantly exhibiting macrophages. Conclusions: The predominance of macrophages in active lesions and the presence of scattered ramified microglia in the center of chronic plaques are consistent with the phagocytic role of macrophages. Meanwhile, the prevalence of ramified microglia at the periphery of chronic active lesions suggests a potential protective function in maintaining lesion stability.

Integrated elemental analysis supports targeting copper perturbations as a therapeutic strategy in multiple sclerosis

Multiple sclerosis (MS) is a debilitating affliction of the central nervous system (CNS) that involves demyelination of neuronal axons and neurodegeneration resulting in disability that becomes more pronounced in progressive forms of the disease. The involvement of neurodegeneration in MS underscores the need for effective neuroprotective approaches necessitating identification of new therapeutic targets. Herein, we applied an integrated elemental analysis workflow to human MS-affected spinal cord tissue utilising multiple inductively coupled plasma-mass spectrometry methodologies. These analyses revealed shifts in atomic copper as a notable aspect of disease. Complementary gene expression and biochemical analyses demonstrated that changes in copper levels coincided with altered expression of copper handling genes and downstream functionality of cuproenzymes. Copper-related problems observed in the human MS spinal cord were largely reproduced in the experimental autoimmune encephalomyelitis (EAE) mouse model during the acute phase of disease characterised by axonal demyelination, lesion formation, and motor neuron loss. Treatment of EAE mice with the CNS-permeant copper modulating compound CuII(atsm) resulted in recovery of cuproenzyme function, improved myelination and lesion volume, and neuroprotection. These findings support targeting copper perturbations as a therapeutic strategy for MS with CuII(atsm) showing initial promise.

Traumatic axonal injury: Clinic, forensic and biomechanics perspectives

Identification of Traumatic axonal injury (TAI) is critical in clinical practice, particularly in terms of long-term prognosis, but also for medico-legal issues, to verify whether the death or the after-effects were attributable to trauma. Multidisciplinary approaches are an undeniable asset when it comes to solving these problems. The aim of this work is therefore to list the different techniques needed to identify axonal lesions and to understand the lesion mechanisms involved in their formation. Imaging can be used to assess the consequences of trauma, to identify indirect signs of TAI, to explain the patient’s initial symptoms and even to assess the patient’s prognosis. Three-dimensional reconstructions of the skull can highlight fractures suggestive of trauma. Microscopic and immunohistochemical techniques are currently considered as the most reliable tools for the early identification of TAI following trauma. Finite element models use mechanical equations to predict biomechanical parameters, such as tissue stresses and strains in the brain, when subjected to external forces, such as violent impacts to the head. These parameters, which are difficult to measure experimentally, are then used to predict the risk of injury. The integration of imaging data with finite element models allows researchers to create realistic and personalized computational models by incorporating actual geometry and properties obtained from imaging techniques. The personalization of these models makes their forensic approach particularly interesting.

Utility of single fibre electromyography (SFEMG)and motor unit number estimation technique (MUNE) in the diagnosis and differentiation of polyneuropathies of different aetiology.

To determine whether single fibre electromyography and motor unit number index can distinguish between axonal and myelin lesions in polyneuropathies. This case-control study was conducted at the Department of Medical Physiology, School of Medicine, University of Duhok, Iraq, and the Neurophysiology Department, Hawler Teaching Hospital, Erbil, Iraq, from January 2021 to March 2022. Group A had patients diagnosed with polyneuropathy regardless of the aetiology, while group B had age-matched healthy controls. Both groups were subjected to single fibre electromyography and motor unit number index as well as conventional nerve conduction study and concentric needle electromyography. Data was analysed using SPSS 26. Of the 140 subjects, 60(43%) were patients in group A; 40(67%) males and 20(33%) females with mean age 55.3±7.2 years. There were 80(57%) controls in group B; 43(54%) females and 37(46%) males with mean age 53.81±7.15. Group A had significantly higher single fibre electromyography jitter, and mean consecutive difference (MCD) values than group B (p<0.05). Group A patients with axonal polyneuropathy had a higher mean jitter (MCD) value (36.476.7ms) than those with demyelinating polyneuropathy (23.262.31 ms) (P <0.05). Patients in group A had a motor unit number index value with a significantly lower mean value (p<0.05) when compared to the controls. Axonal polyneuropathy patients had a lower MUNIX value (99.612.8) than demyelinating polyneuropathy patients (149.845.7) (P< 0.05). Single fibre electromyography and motor unit number index could help differentiate between the pathophysiology of axonal and demyelinating polyneuropathy.

Nerve injuries due to fractures in childhood : Primarily and secondarily on the upper extremity

The approach for nerve injuries in children in the context of fractures of the upper extremities is inconsistent in the literature. The underlying mostly retrospective studies do not usually consider the potential diagnostics. The frequency of nerve injuries with aclear need for reconstructive surgery is sometimes estimated so differently that precedent-setting errors in these studies must be assumed; however, as 10-20% of pediatric fractures near the elbow show primary or secondary nerve lesions, timely and appropriate further treatment is necessary. An overview concerning diagnostic tools with an explanation of potential results and an algorithm with atimeline for diagnostic and therapeutic management are presented. Good results after nerve lesions can only be achieved when timely diagnostics without delay and correct detection of axonal lesions which benefit from surgical treatment are carried out.

Differential diagnosis of acute flaccid paralysis in children with Guillain—Barré syndrome and neuromyelitis optica spectrum disorder: Clinical cases

Background. Acute flaccid paralysis is a clinical syndrome characterized by a sudden onset of weakness in one or more limbs with decreased or absent tendon reflexes in the affected limbs. This condition may be a manifestation of such pathologies as Guillain-Barré syndrome and neuromyelitis optica spectrum disorder. Clinical cases description. We describe two clinical cases of Guillain-Barré syndrome in patient M., 7 years old, and neuromyelitis optica spectrum disorder in patient D., 3 years old. In both children, the main clinical manifestation was acute flaccid paralysis. Patient M. was admitted to the Neurological Department of the Moscow Regional Center for Maternity and Childhood Protection with complaints of sharp pronounced weakness in the limbs, inability to walk. According to the disease history, the patient had an acute respiratory viral infection in October 2022. The conducted neurologic examination revealed decreased muscle tone and muscle strength in all limbs, absence of reflexes from the lower limbs. A liquor test was conducted, which revealed increased protein contents. Electroneuromyography detected a pronounced axonal lesion of all motor fibers in the arms and legs. The formulated diagnosis was “Guillain-Barré syndrome, variant of acute motor axonal neuropathy.” The treatment with plasmapheresis and intravenous immunoglobulins showed positive dynamics. In the second case, patient D. was admitted to the Pediatric Infectious Disease Department of Naro-Fominsk Hospital with similar complaints of sharp weakness in the limbs. Neurological examination showed a diffuse decrease in muscle tone, absence of reflexes from all limbs. Elevated protein contents were determined in the liquor. MRI of the cervical spinal cord showed myelitis of segments C3–C7. Negative antibodies to aquaporin-4 were found. The patient was treated with ceftriaxone, methylprednisolone, and plasmapheresis. Then he was transferred to the Neurological Department of the Moscow Regional Center for Maternity and Childhood Protection, where a repeated MRI of the cervicothoracic spinal cord revealed, in addition to myelitis at the level of C3–C7, a lesion of segments from the level of C2 to the medulla oblongata. The formulated diagnosis was “Neuromyelitis optica spectrum disease, seronegative form. Flaccid tetraparesis.” The continued treatment with prednisolone and intravenous immunoglobulin produced positive effect. Conclusion. The presented clinical cases will help neurologists to improve timely diagnosis and treatment of causes of acute flaccid paralysis in children, thereby reducing possible complications, disability, and mortality.

Neurolymphomatosis in Non-Hodgkin's Lymphoma

non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of hematopoietic puffins, with diphun B-velicocyclotinous lymphoma accounting for 25% of all NHLs and having the greatest midline to axis growth (Leeuwenуе et al., 2014). Of all NHLs, the central and peripheral nervous systems are most often affected in diphytic B-lycocytic lymphoma (Padala, &amp; Kallam, 2022. Liu, &amp; Barta, 2019). In NHL, infiltration of cranial and peripheral nerves can be detected - neurolymphomatosis (NL) emerges. NL is a very rare condition and occurs in about 0.2% of patients with NHL (Baehring, Damek, Martin, Betensky &amp; Hochberg, 2003). These infiltrations can manifest with detection of mononeuropathy, multiple neuropathy, symmetric neuropathy or plexopathy (Grisold W., Grisold A., Marosi, Meng, &amp; Briani, 2015). The aim of the work was to study the features of the clinical course, diagnosis and treatment of neurolymphomatosis in the form of lesions of the trigeminal, facial cranial nerve and the left ulnar nerve in diffuse B-bollichelial non-Hodgkin lymphoma based on a clinical case. We present a review of a clinical case of peripheral nervous system involvement in a patient born in 1977 with diffuse B-cell non-Hodgkin's lymphoma. The diagnosis was established on the basis of clinical manifestations of lesions of the branches of the trigeminal and left facial nerves, the left ulnar nerve, magnetic resonance imaging of the head and brain, electroneuromyography, and immunohistochemical examination of the infiltrate biopsy from the affected buccal branch of the left facial nerve. In March 2022, the patient developed moderate peripheral paresis of the mimic muscles on the left side, burning pain with impaired tactile and pain sensitivity of the dorsum, wing of the nose, and left instep. A week later there was a decrease in the strength, tactile and pain sensitivity, and patience of the fourth and fifth fingers of the left hand. Within a month, the burning pain had spread to the left cheek, periorbital, and chin areas of the face. In 2021, the patient was diagnosed with B-bollichelial non-Hodgkin's lymphoma with involvement of the right axillary, supraclavicular lymph nodes, left breast, followed by chemotherapy and clinical remission. Magnetic resonance imaging of the head revealed a perineural lesion of the third branch of the right trigeminal nerve, the second branch of the left trigeminal nerve, and the cheek branch of the left facial nerve. Electroneuromyography revealed an axonal lesion of the left ulnar nerve. The results of examination of the infiltrate biopsy from the affected buccal branch of the facial nerve specimens confirmed non-Hodgkin's diffuse B-cell lymphoma, GCB-phenotype and nerve damage due to NHL. Treatment of multiple neuropathy with glucocorticosteroids, nonsteroidal anti-inflammatory drugs, acelicholinesterase inhibitors, and specific chemotherapy resulted in limited therapeutic effect. Prescribing pregabalin resulted in decreased reduction of neuropathic facial pain. Thus, neurolymphomatosis is a rather rare manifestation of non-Hodgkin's lymphomas, the use of magnetic resonance imaging of the head and brain as well as immunohistochemical examination of the affected nerve infiltrate biopsy is important to confirm the diagnosis.&#x0D; In the Ukrainian scientific medical literature, there are few descriptions of cases of neurolymphomatosis in NHL, although they occur in patients, and it is necessary to describe in more detail the peculiarities of the collicular course of the diagenesis and treatment in these cases.

Diagnosis and Treatment of Multiple Sclerosis: What may be new ?

Up to now, Diagnosis and therapy of multiple sclerosis (MS) are not optimal, they need improvement. We present a diagnostic parameter and two therapeutic methods that offer a prospect of success without burdening the patient. They are the biomarker Nf-L for the evaluation of the status of the lesions of the neural axons and the application of two treatment methods of endogenous origin: PEA (N-Palmitoylethanolamin) and intracellular Enzymes. They are suitable for MS in terms of their effects. The good experience gained so far suggests that it would be worthwhile to test them in detailed studies.

Multiple sclerosis: progress in detection and therapy?

Diagnosis and therapy of multiple sclerosis (MS) are not optimal so far, they need improvement. We present a diagnostic parameter and two therapeutic methods that offer a prospect of success without burdening the patient. They are the biomarker Nf-L for the evaluation of the status of the lesions of the neural axons and the application of two treatment methods of endogenous origin: PEA (N-Palmitoylethanolamin) and intracellular Enzymes. They are suitable for MS in terms of their effects. The good experience gained so far suggests that it would be worthwhile to test them in detailed studies.

Before blaming SARS-CoV-2 for GBS, other causes should be ruled out.

We read with interest the article by Parikh et al.[1] about a 2.5-year-old female patient who developed progressive, flaccid quadriparesis that resulted in being unable to stand or walk. Work-up revealed positive IgG-antibodies against SARS-CoV-2, demyelinating neuropathy, and dissociation cyto-albumin.[1] Guillain–Barre syndrome (GBS) was diagnosed and intravenous immunoglobulins (IVIG) were given with little benefit.[1] The study is appealing but raises concerns. We disagree with the diagnosis of acute SARS-CoV-2 infection.[1] The patient tested negative for SARS-CoV-2 in the PCR and the rapid antigen test (RAT).[1] Only neutralizing IgG antibodies were elevated.[1] Given that neutralizing antibodies can persist for months,[2] it cannot be ruled out that SARS-CoV-2 infection may have occurred already weeks or months before the onset of GBS, suggesting a causal relationship between SARS-CoV-2 and GBS rather unlikely. Further arguments against acute SARS-CoV-2 infection are that the history was negative for pulmonary or gastrointestinal infections shortly before the onset of GBS,[1] the lymphocyte count was normal, and no other stigmata of COVID-19 were present.[1] Acute SARS-CoV-2 infections are often associated with lymphopenia.[3] We disagree with the interpretation of nerve conduction studies as “demyelinating.” According to Table 1, nerve conduction velocities in the median, ulnar, peroneal, and tibial nerves were within normal limits.[1] The findings in Table 1 are more suggestive of an axonal lesion;[1] therefore, the diagnosis should be acute, motor, axonal neuropathy (AMAN) rather than acute, inflammatory demyelinating polyneuropathy (AIDP). We disagree with the statement in the discussion that there were no abnormalities on follow-up.[1] No results of follow-up investigations were given in the case description.[1] The patient was discharged with severe paraparesis (muscular research council [MRC] 2/5 respectively 3/5).[1] We should know the period in which neurological abnormalities have completely disappeared. Because muscle strength in the lower limbs hardly improved (MRC 2/5 bilaterally at onset, MRC 2/5 respectively 3/5 at discharge), IVIGs can be rated as rather ineffective. We should know if ever plasmapheresis was considered. Additionally, GBS patients who do not respond to treatment should be evaluated for nodopathy.[4] and it should be borne in mind that about one-third of GBS patients have no causative agent. Because the patient had difficulty sitting down,[1] involvement of the axial muscles cannot be ruled out. Because respiratory muscles are often affected along with the axial muscles, we should be informed if there was any evidence of muscular respiratory insufficiency. Were oxygen saturation and lung function tests within normal limits? The results of the virus panels are missing.[1] We should know which viral infections have been ruled out. Given that GBS is often triggered by previous viral infections,[5] ruling them all out is imperative. Even in the absence of a gastrointestinal infection, the patient must be tested for antibodies to Campylobacter jejuni and Mycoplasma pneumoniae.[5] Overall, the interesting study has limitations that challenge the results and their interpretation. Diagnosing COVID-19 requires a positive PCR. A causal connection between SARS-CoV-2 and GBS can only be established if a temporal connection between the infection and the onset of neurological compromise can be demonstrated. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Ethics approval Ethics approval was in accordance with ethical guidelines. The study was approved by the institutional review board. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Microfluidic Platforms Promote Polarization of Human-Derived Retinal Ganglion Cells That Model Axonopathy.

Axons depend on long-range transport of proteins and organelles which increases susceptibility to metabolic stress in disease. The axon initial segment (AIS) is particularly vulnerable due to the high bioenergetic demand of action potential generation. Here, we prepared retinal ganglion cells derived from human embryonic stem cells (hRGCs) to probe how axonal stress alters AIS morphology. hRGCs were cultured on coverslips or microfluidic platforms. We assayed AIS specification and morphology by immunolabeling against ankyrin G (ankG), an axon-specific protein, and postsynaptic density 95 (PSD-95), a dendrite-specific protein. Using microfluidic platforms that enable fluidic isolation, we added colchicine to the axon compartment to lesion axons. We verified axonopathy by measuring the anterograde axon transport of cholera toxin subunit B and immunolabeling against cleaved caspase 3 (CC3) and phosphorylated neurofilament H (SMI-34). We determined the influence of axon injury on AIS morphology by immunolabeling samples against ankG and measuring AIS distance from soma and length. Based on measurements of ankG and PSD-95 immunolabeling, microfluidic platforms promote the formation and separation of distinct somatic-dendritic versus axonal compartments in hRGCs compared to coverslip cultures. Chemical lesioning of axons by colchicine reduced hRGC anterograde axon transport, increased varicosity density, and enhanced expression of CC3 and SMI-34. Interestingly, we found that colchicine selectively affected hRGCs with axon-carrying dendrites by reducing AIS distance from somas and increasing length, thus suggesting reduced capacity to maintain excitability. Thus, microfluidic platforms promote polarized hRGCs that enable modeling of axonopathy. Microfluidic platforms may be used to assay compartmentalized degeneration that occurs during glaucoma.

Clinical-immunological and neurophysiological correlations in paraneoplastic polyneuropathy caused by small cell lung cancer

Objective. To study the correlation between the neurological, immunological and neurophysiological signs of paraneoplastic polyneuropathy (PPNP) caused by small cell lung cancer (SCLC), to improve the quality of diagnosis of this pathology.Materials and methods. Clinical, immunological (anti-Hu) and neurophysiological (electromyography (EMG), electroneuromyography (ENMG), somatosensory evoked potentials (SSEP)) examination of 61 patients with PPNP caused by SCLC are presented.Results. It was established that sensory disorders in the limbs are the first and obligate clinical symptoms of PPNP, which precede the initial diagnosis of SCLC in 56% in 3-12 months, characterized by a predominance of a decrease in surface sensitivity in the form of distal hypoesthesia in 70% of cases. The motor form is characterized by an older age (67 years) than the sensory (60 years) and sensorimotor (58.0 years, p &lt;0,05). Motor disorders in the limbs occur in 46% of cases, manifested by mild symmetrical distal paresis of the legs and subclinical damage to the motor nerves of the upper extremities according to the results of ENMG (p &lt;0,001). Detection of anti-Hu in plasma is highly correlated with a significant increase in latency and a decrease in amplitudes component N22 in the conduct of SSEP, which indicates the defeat of the axons of the sensory nerves of the limbs (p &lt;0,05). Changes in amplitude parameters, with preserved speed indicators of nerves according to the results of ENMG indicate an axonal type of lesion (p &lt;0,05), which, in combination with the detection of anti-Hu in plasma, are pathognomonic signs of the paraneoplastic nature of the process.Conclusion. As a result of the study, clinical, immunological and neurophysiological features of various forms of PPNP were identified. The obtained correlations make it possible to diagnose the corresponding type of nerve pathology more accurately and in a timely manner and to suspect the development of oncological disease in time. The revealed changes in the indicators of the N22 component of SSEP can serve as a marker of axonal lesion of peripheral nerves, which with high diagnostic efficiency justifies the expediency of inclusion in the protocol of the ENMG study for verification of additional signs characteristic of PPNP.

Adult-Onset Leukoencephalopathy with Axonal Spheroid and Pigmented Glia: Different Histological Spectrums Presented in Autopsy Cases of Siblings and a Surgical Case of Stereotactic Biopsy

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia encompasses hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented orthochromatic leukodystrophy. We describe the clinicopathological and genetic findings of three patients with this disorder. All patients presented with dysarthria, with or without cognitive decline. The first and second patients were siblings who died of the disease at ages 42 and 54, respectively, while the third patient has been bedridden. Brain magnetic resonance imaging revealed T2 hyperintensities in the subcortical and periventricular white matter. Pathological diagnosis was established by brain autopsy in cases 1 and 2, and a stereotactic brain biopsy in case 3, followed by genetic analysis of colony stimulating factor-1 receptor gene. A heterozygous c.2345G > A (p.R782H) variant was identified in the autopsy-proven cases, and a c.1765G > A (p.G589R) variant in the biopsy-proven case. Postmortem examination revealed severe white matter degeneration involving the bilateral frontoparietal lobes, but sparing the subcortical U-fibers. All cases revealed widespread loss of myelinated axons in the white matter lesions; however, axonal spheroids and pigmented macrophages were abundant in cases 1 and 3 and much less in case 2. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia should be considered in patients with presenile dementia and diffuse white matter lesions.

Correlation between retinal structure and brain multimodal magnetic resonance imaging in patients with Alzheimer's disease.

The retina imaging and brain magnetic resonance imaging (MRI) can both reflect early changes in Alzheimer's disease (AD) and may serve as potential biomarker for early diagnosis, but their correlation and the internal mechanism of retinal structural changes remain unclear. This study aimed to explore the possible correlation between retinal structure and visual pathway, brain structure, intrinsic activity changes in AD patients, as well as to build a classification model to identify AD patients. In the study, 49 AD patients and 48 healthy controls (HCs) were enrolled. Retinal images were obtained by optical coherence tomography (OCT). Multimodal MRI sequences of all subjects were collected. Spearman correlation analysis and multiple linear regression models were used to assess the correlation between OCT parameters and multimodal MRI findings. The diagnostic value of combination of retinal imaging and brain multimodal MRI was assessed by performing a receiver operating characteristic (ROC) curve. Compared with HCs, retinal thickness and multimodal MRI findings of AD patients were significantly altered (p < 0.05). Significant correlations were presented between the fractional anisotropy (FA) value of optic tract and mean retinal thickness, macular volume, macular ganglion cell layer (GCL) thickness, inner plexiform layer (IPL) thickness in AD patients (p < 0.01). The fractional amplitude of low frequency fluctuations (fALFF) value of primary visual cortex (V1) was correlated with temporal quadrant peripapillary retinal nerve fiber layer (pRNFL) thickness (p < 0.05). The model combining thickness of GCL and temporal quadrant pRNFL, volume of hippocampus and lateral geniculate nucleus, and age showed the best performance to identify AD patients [area under the curve (AUC) = 0.936, sensitivity = 89.1%, specificity = 87.0%]. Our study demonstrated that retinal structure change was related to the loss of integrity of white matter fiber tracts in the visual pathway and the decreased LGN volume and functional metabolism of V1 in AD patients. Trans-synaptic axonal retrograde lesions may be the underlying mechanism. Combining retinal imaging and multimodal MRI may provide new insight into the mechanism of retinal structural changes in AD and may serve as new target for early auxiliary diagnosis of AD.

Astrocytosis, Inflammation, Axonal Damage and Myelin Impairment in the Internal Capsule following Striatal Ischemic Injury.

Secondary degeneration is defined as a set of destructive events that damage cells and structures that were initially spared or only peripherally affected by the primary insult, constituting a key factor for functional impairment after traumatic brain injury or stroke. In the present study, we evaluated the patterns of astrocytosis, inflammatory response, axonal damage and oligodendrocytes/myelin impairment in the internal capsule following a focal injection of endothelin-1 (ET-1) into the dorsal striatum. Animals were perfused at 1, 3 and 7 post-lesion days (PLD), and tissue was processed to immunohistochemistry for neutrophils (MBS1), macrophages/microglia (ED1), astrocytes (GFAP), axonal lesion (βAPP), oligodendrocytes (Tau) and myelin (MBP). A significant number of neutrophils was observed at 1PLD, followed by intense recruitment/activation of macrophages/microglia at 3PLD and astrocytic reaction with a peak at 7PLD. Oligodendrocyte damage was pronounced at 3PLD, remaining at 7PLD. Progressive myelin impairment was observed, with reduction of immunoreactivity at 7PLD. Axonal lesion was also identified, mainly at 7PLD. Our results indicate that acute inflammatory response elicited by the ischemic insult in the striatum can be associated with the axonal impairment and damage of both oligodendrocytes and myelin sheath identified in the internal capsule, which may be related to loss of tissue functionality observed in secondary degeneration.

Post-traumatic epilepsy in Cameroon: a retrospective study in a referral hospital

BackgroundPost-traumatic epilepsy is defined as the onset of at least one seizure beyond the first week following a traumatic brain injury (TBI). High prevalence of TBI in our setting may contribute to the burden of epilepsy in adult population. This is a retrospective review of medical records of patients admitted from January 1st, 2010 to December 31st, 2019) at Douala General Hospital. We included patients aged ≥ 18 years with seizure onset at least one week after TBI. Incomplete files and previously known epilepsy were excluded. Data on sociodemography, clinical and para-clinical features, treatment and outcome were analysed using R software version 36.2.ResultsWe finally included 65 patients with post-traumatic epilepsy among 993 medical records of epilepsy. The mean age was 35.1 ± 12.6 years, with 64.6% of male. Road traffic accident was the main aetiology of brain trauma (78.5%), resulting in haemorrhagic contusions (21.5%), sub-dural haematoma (15.4%), and diffuse axonal lesions (15.4%) mainly. Seizure onset was within 2 years post-trauma in 73.8% of cases. Generalized tonic–clonic seizures were the commonest seizure’s type. Electroencephalogram was abnormal in 81%, including 47% of focal discharges. Antiepileptic drugs were mainly sodium valproate, carbamazepine, and phenobarbital. Seizure freedom was obtained in 67.7% of cases.ConclusionsPost-traumatic epilepsy is a heterogeneous, frequent and often disabling complication of traumatic brain injury. Road traffic accident is the main cause of brain trauma. It affects a young and active population. About half of cases presented GTCS. With antiepileptic drugs, more than two-thirds of patients become seizure-free.

Epigenomic Profiling of Dorsal Root Ganglia upon Regenerative and Non-regenerative Axonal Injury.

RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and assay for transposase-accessible chromatin sequencing (ATAC-seq) are genome-wide techniques that provide information relative to gene expression, chromatin binding sites, and chromatin accessibility, respectively. Here we describe RNA-seq, H3K9ac, H3K27ac and H3K27me3 ChIP-seq, and ATAC-seq in dorsal root ganglia (DRG) after sciatic nerve or dorsal column axotomy, to characterize the transcriptional and epigenetic signatures of DRG upon regenerative vs non-regenerative axonal lesion.

487: A NEW TOOL TO EVALUATE THE OPTIMAL ABP THROUGH THE INTRACRANIAL PRESSURE PULSE WAVEFORM

Introduction: Cerebral hemodynamics is an important parameter to be considered in the management of critically ill patients, unfortunately this information is not accessible to all physicians. This text will describe the use of the noninvasive sensor to monitor intracranial compliance (ICC), through the evaluation of the intracranial pressure pulse morphology (ICPwf), to adjust the arterial blood pressure (ABP) bedside. Methods: Non-invasive brain4care technology for ICC monitoring was used for the determination of appropriate ABP ranges for cerebral autoregulation. This new tool consists of a sensor positioned on the patient’s scalp and an algorithm which transforms the ICPwf in 2 numbers: P2/P1 ratio and time to peak. Results: Case1. Male patient, 40 yo with septic shock and neurological decline. The ABP was adjusted by the ICPwf analysis, the first monitoring shows an abnormal ICPwf (P2/P1 ratio of 0.56), suggesting reduced perfusion. The mean ABP was raised from 68mmHg to 90mmHg, resulting in a normal ICPwf (P2/P1 ratio of 0.81). The patient had an excellent outcome, alternating the GCS of 4 to 10 within 24 hours. Case 2. Male patient, 67 yo, head trauma due to fall from her own height. TC showed bitemporal contusion, acute subdural hematoma and midline deviation. ABP values between 75 and 85mmHg showed best ICC, confirmed by TCD. The ABP target was maintained without improvement of Glasgow Come Scale (9) and P2/P1 ratio higher than 1.2, suggestive of intracranial hypertension. A lumbar puncture was done (30ml of CSF was removed) the result was a P2/P1 ratio of 0.9, improvement of the patient’s cognitive status and better arterial blood flow velocity detected by TCD. After 14 days the patient was transferred to a rehabilitation. Case 3. Male patient, 17 yo, a victim of a car accident with GCS of 3 at scene. TC indicates diffuse axonal lesion, swelling and subgaleal hematoma. The ABP with best intracranial compliance was between 70 and 85mmHg. The patient was discharged from the ICU 16 days after the accident. Conclusions: The sensor was applicable to all patients, presenting practicality and safety. The information allowed better management and safety to the patient and physicians, optimization of procedures and pertinence in the conduct.

Case report: radiation-induced lumbosacral plexopathy – a very late complication of radiotherapy for cervical cancer

BackgroundLumbosacral plexopathy caused by radiotherapy is a rare but severe consequence of cancer treatment. This condition often leads to varying degrees of sensory and motor impairment. Neurological complications, which are typically permanent, manifest a long period after irradiation.Case presentationWe describe a case of progressive lower extremity weakness and sensory impairment in a woman who had been effectively treated with radiotherapy for cervical cancer with development 36 years after irradiation. The electrophysiological assessment revealed a subacute bilateral axonal lesion of the lumbosacral plexus. None of the clinical manifestations, serology, cerebrospinal fluid or imaging data discovered an explanation other than radiation-induced lumbosacral plexopathy (RILP).ConclusionsThis case demonstrates that RILP may emerge more than 30 years after the radiotherapy.

СИНДРОМ ГИЙЕНА-БАРРЕ, АССОЦИИРОВАННЫЙ С COVID-19 В РЕСПУБЛИКЕ САХА (ЯКУТИЯ)

Guillain-Barre syndrome (GBS) is a rare, severe disease of peripheral nerves and nerve roots, which is usually caused by infections. Since the beginning of the pandemic of the new coronavirus infection COVID-19, numerous cases of Guillain-Barre syndrome have been presented in scientific publications, which developed in patients at various times after suffering the new coronavirus infection. The purpose of this study was to investigate the features of the development and course of GBS associated with COVID-19. Nine patients with an established diagnosis of GBS were examined, with six of them being infected with the SARS-CoV2 virus. A comparative study of the features of the course and severity of the disease was carried out in two groups: the main group – GBS associated with COVID-19; and the control group – GBS without COVID-19. Based on the data obtained, it can be said that GBS against the background of the new coronavirus infection develops more often in men over the age of 50 and proceeds much more severely than GBS unrelated to COVID-19. Axonal lesions with a longer and incomplete recovery of motor functions, with the development of severe respiratory failure requiring prolonged ventilation, were significantly more common in patients with COVID-19.