Layers Of Nerve Research Articles

Remodelling of the lamina cribrosa thickness in proliferative diabetic retinopathy as a pathogenetic factor of retrolaminar migration of silicone oil after vitrectomy

Aims/Purpose: to analyse the relationship of lamina cribrosa (LC) thickness in patients with proliferative diabetic retinopathy (PDR) after vitrectomy with SiO tamponade with retrolaminar migration of intraocular silicone oil (SiO).Methods: This retrospective study included 35 patients with PDR after vitrectomy with SiO tamponade who underwent unenhanced head computed tomography for various clinical indications. All images were visually evaluated for subretinal and retrolaminar migration of SiO involving the anterior visual pathway (optic nerve, optic chiasm, and optic tract) and the ventricular system. LC thickness was measured with spectral domain optical coherent tomography (SD OCT) using LC_Thickness_programm.m and main_low_noise_filters_programm.m, based on the adaptive compensation algorithm for eliminating a high‐level noise in the deep layers of optic nerve and improving the visualization of the LC posterior border, as well as for processing B‐scan with a set of 3 digital filters: Butterworth Low‐pass Filter inverion image, Wavelet Low‐pass Filter Analysis Daubechies original and inversion image.Results: In our patients with PDR the average LC thickness was 697 ± 35 μm (589 to 768 μm), that was 1.9 times higher than in healthy people (p < 0.001). We detected subretinal and retrolaminar silicone oil migration in 10 of the 35 patients (28.57%), noting silicone oil at the optic nerve head (n = 2), retrolaminar optic nerve (n = 4), optic chiasm (n = 2), optic tract (n = 1) and in the lateral ventricles (n = 3). 3 patients had migration to 2 locations each (1 – in retrolaminar optic nerve and optic chiasm, 2 – in retrolaminar optic nerve and lateral ventricle). We compared the LC thickness of patients without and with subretinal and retrolaminar SiO migration. It was established that LC thickness of patients with subretinal and retrolaminar SiO migration was significantly less (589 to 658 μm) than in patients without SiO migration (673 to 768 μm). It should be noted that the number of cases positive for migration was small, limiting the statistical power and accuracy of the prevalence.Conclusions: A direct correlation between scleral LC thickness and retrolaminar migration of SiO in patients with PDR after vitrectomy with SiO tamponade was revealed.

Multidisciplinary Study Based on Clinical, Electrophysiological and Psycological Evaluations Combined with Advanced Neuroimaging in Gaucher Disease Patients

Gaucher Disease (GD) is an autosomal recessive metabolic disorder due to glucocerebrosidase deficit. There are three main clinical phenotypes: type I (GD1: non-neuronopathic form), characterized by a visceral involvement that can mimic a hematologic disease; type II (GD2: acute neuropathic form) and type III (GD3) characterized by a slower and progressive neurological involvement. Hematologists have often involved in diagnosis and management of the GD1 patients. Increasing data and our experience show that patients with GD1 may present manifestations of Parkinson's disease or Parkinsonism symptoms (tremor, bradykinesia and rigidity), frequently combined with cognitive impairment and behavioral alterations. The aim of this study is to deeply investigate the neurological and neuropsychiatric aspects in GD1 patients in order to identify clinical and subclinical neurological manifestations, including cognitive impairment and behavioral alterations in this category of patients. This observational, monocentric, and prospective study is planned to enroll 22 GD patients (19 GD1 patients and 3 GD3 patients with or without active neurological signs) aged >12 years. Neurological assessments include: clinical evaluation including Severity Scoring Tool Unified Parkinson's Disease Rating scale and Epworth Sleepiness scale, psycho-diagnostic tests and psychiatric evaluation using cognitive test battery and two psychiatric (BPRS) and psychological (CBA 2.0) questionnaires, Somatosensory and Motors Evoked Potentials, Electroencephalography (EEG) and magnetic resonance (MR) 3Tesla, at baseline, after 12 months and 24 months. Preliminary results concerning the baseline evaluation of first cohort of patients are here reported. Since June 2019, 11 patients (10 GD1 and 1 symptomatic GD3) have been enrolled. Neurological impairment according to the major features (Gaucher severity score tool) was found in 4/11 patients: signs of Parkinson disease in 1 GD1 patient, motoneuron disease in 1 GD3 patients, abnormalities in ocular motility and psycho-cognitive disturbances in 2 GD1 patients. Minor features of a neurological impairment was found as follows: bradykinesia in 5 GD1 patients, excessive daytime sleepiness in 5 GD1 patients, and saccadic slowness in 1 GD1 patient. EEG revealed focal or diffuse slow waves in 6 patien patients (5 GD1 and 1 GD3). Cognitive and psychological evaluations revealed the presence of significant psychiatric symptoms such as depression, anxiety, and physical concerns. Six patients (5 GD1and 1 GD3) surprisingly had sensorineural hearing loss. Auditory Brainstem Response revealed abnormal disyncrony-like morphology and central speech processing in noise in 3 GD1 and in 4 (3 GD1 and 1 GD3) patients, respectively. Ophthalmological evaluation highlighted a normal visus and intraocular pressure in all patients. Moderate alterations of the fundus were present in 2 patients (1 GD1 and 1 GD3) and superficial corneal dystrophies in 3 (2 GD1 and 1 GD3) patients. An increased latency and moderate reduction in the amplitudes of optic nerve function were found in all tested patients. The retinal responses to the Electroretinogram exam were of excellent quality in all but one GD1 patient, who showed slightly reduced responses. The spectral domain-optical coherence tomography (SD-OCT) examination showed posterior pole alterations in 3 patients (2 GD1 and 1 GD3) and borderline nerve fiber layers of the optic nerve (RNFL) in 3 (2 GD1 and 1 GD3) cases. Our clinical study represents quite an innovative one, since neurological investigations are focused on GD2 and GD3 phenotypes. Neurological involvement with different phenotypical aspects were also found in GD1 patients. Sensorineural hearing loss and central alteration of auditory processing were present in higher incidence compared to the unaffected population. Psychological data din't show significant cognitive impairments, but pointed out some psychiatric aspects, such as anxiety, depression and somatic concerns. MR 3Tesla can be an important tool to better understand these data. Evaluation of the remaining cohort of patients and longer follow-up could confirm that neurological involvement is not exclusive of the type 3 GD. Disclosures No relevant conflicts of interest to declare.

Correlation Between Ischemic Retinal Accidents and Radial Peripapillary Capillaries in the Optic Nerve Using Optical Coherence Tomographic Angiography: Observations in 6 Patients.

Background:Perfusion of the optic nerve has been widely studied using fluorescein angiography (FAG), which is currently regarded as the criterion standard. However, FAG has adverse effects associated with intravenous contrast administration and is limited in its capacity to characterize and stratify the different vascular layers of the optic nerve and retina. The use of new imaging techniques, such as optical coherence tomographic angiography (Angio-OCT), is therefore important.Aim:A qualitative description is made of the vascular layers of the optic nerve and of how vascular events affect radial peripapillary capillaries (RPC). Two patients with central retinal artery occlusion (CRAO), 1 with arteritic anterior ischemic optic neuropathy (AAION), and 3 healthy subjects were studied.Results:The Angio-OCT imaging afforded better visualization of the depth of the RPC and rest of the vascular layers of the retina compared with FAG. Optic nerve surface perfusion was affected in AAION and proved normal in CRAO.Conclusions:Our results indicate that perfusion of the papilla and RPC mainly arises from the papillary plexus that depends on the posterior ciliary artery.

Murine and human tissue-engineered esophagus form from sufficient stem/progenitor cells and do not require microdesigned biomaterials.

Tissue-engineered esophagus (TEE) may serve as a therapeutic replacement for absent foregut. Most prior esophagus studies have favored microdesigned biomaterials and yielded epithelial growth alone. None have generated human TEE with mesenchymal components. We hypothesized that sufficient progenitor cells might only require basic support for successful generation of murine and human TEE. Esophageal organoid units (EOUs) were isolated from murine or human esophagi and implanted on a polyglycolic acid/poly-l-lactic acid collagen-coated scaffold in adult allogeneic or immune-deficient mice. Alternatively, EOU were cultured for 10 days in vitro prior to implantation. TEE recapitulated all key components of native esophagus with an epithelium and subjacent muscularis. Differentiated suprabasal and proliferative basal layers of esophageal epithelium, muscle, and nerve were identified. Lineage tracing demonstrated that multiple EOU could contribute to the epithelium and mesenchyme of a single TEE. Cultured murine EOU grew as an expanding sphere of proliferative basal cells on a neuromuscular network that demonstrated spontaneous peristalsis in culture. Subsequently, cultured EOU generated TEE. TEE forms after transplantation of mouse and human organ-specific stem/progenitor cells in vivo on a relatively simple biodegradable scaffold. This is a first step toward future human therapies.

Morphometric analysis of connective tissue sheaths of sural nerve in diabetic and nondiabetic patients.

One of the most common complications of diabetes mellitus is diabetic neuropathy. It may be provoked by metabolic and/or vascular factors, and depending on duration of disease, various layers of nerve may be affected. Our aim was to investigate influence of diabetes on the epineurial, perineurial, and endoneurial connective tissue sheaths. The study included 15 samples of sural nerve divided into three groups: diabetic group, peripheral vascular disease group, and control group. After morphological analysis, morphometric parameters were determined for each case using ImageJ software. Compared to the control group, the diabetic cases had significantly higher perineurial index (P < 0.05) and endoneurial connective tissue percentage (P < 0.01). The diabetic group showed significantly higher epineurial area (P < 0.01), as well as percentage of endoneurial connective tissue (P < 0.01), in relation to the peripheral vascular disease group. It is obvious that hyperglycemia and ischemia present in diabetes lead to substantial changes in connective tissue sheaths of nerve, particularly in peri- and endoneurium. Perineurial thickening and significant endoneurial fibrosis may impair the balance of endoneurial homeostasis and regenerative ability of the nerve fibers. Future investigations should focus on studying the components of extracellular matrix of connective tissue sheaths in diabetic nerves.

Utilization of Sonography Compared With Magnetic Resonance Imaging in Determining the Cross-Sectional Area of the Median Nerve in a Sample of Working Macaca fascicularis

A preclinical study of 15 Macaca fascicularis monkeys was conducted to determine (1) the ability of detecting median mononeuropathy (MMN) within the median nerve after a work intervention and (2) the relationship between the layers of the median nerve during an acute inflammatory process by using sonography in conjunction with magnetic resonance imaging (MRI). Cross-sectional areas (CSAs) were imaged using MRI and sonography proximal to the carpal tunnel inlet (defined by the most distal portion of the radius) and further distal into the carpal tunnel (defined by the most proximal portion of the pisiform) at the prework exposure stage. CSAs measured on the outer edge of the median nerve were obtained from both modalities, at both anatomical locations. An intermodality t test demonstrated no statistical differences between the two sets of measurements (radius, P ≤ .15; pisiform, P ≤ .46). At the postwork exposure stage, sonographic measurements were obtained on the outer and inner borders of the median nerve at both anatomical levels. A two-tailed t test showed statistically significant differences within the carpal tunnel comparing pre- and postwork CSA measurements (radius, P ≤ .01; pisiform, P ≤ .297). The epineurial layer area was then determined as the difference between outer-border and inner-border CSAs. Pearson correlations between the epineurial layer and overall median nerve CSA within the carpal tunnel demonstrated a strong positive correlation that was statistically significant ( r = 0.97; P ≤ .01) after postwork exposure. Possible factors contributing to this acute phase of MMN could be hyperemia within the layers of the nerve and the development of Renault bodies. This work would need to be translated to human studies for further confirmation of the anatomic and clinical significance of this effect.

Leiomyosarcoma involving the sciatic nerve: Case report and review of the literature

Soft tissue sarcomas (STSs) represent 1% and 15% of adult and pediatric tumors, respectively, and almost 75% of all sarcomas; primary STSs occur commonly in the lower extremities. Leiomyosarcomas originate from the malignant transformation of a smooth muscle cell, which in turn may arise from a pluripotent mesenchymal stem cell. The present case report describes a patient with a leiomyosarcoma arising from the posterior thigh musculature, which invaded all layers of the left sciatic nerve's tibial division. Only two similar case reports exist in the literature, documenting sciatic nerve involvement by a leiomyosarcoma. The current patient underwent preoperative fractionated external beam radiation therapy (FEBRT) to the tumor and then had its removal which resulted in a 12 cm resection of the tibial division of the sciatic nerve. This defect was repaired with an intrafascicular sural nerve graft. Postoperatively, she had weakness of left hip flexion, dorsi- greater than plantar flexion, and left eversion, all of which reverted to normal after approximately two years. After surgery, the patient received further FEBRT, developed pulmonary involvement by leiomyosarcoma and underwent bilateral thoracotomies with removal of all nodules. She underwent chemotherapy (CTX) with ifosfamide and doxorubicine, the latter switched to epirubicin, but developed a new pulmonary nodule five months after CTX completion. Other CTX trials were unsuccessful, and she succumbed five years after her original extremity tumor complete resection.

Implantable CMOS neuro-stimulus chip for visual prosthesis

A prototype chip with 2×2 pixels for implanting in blind patients affected by outer retinal degeneration is presented in this paper. This visual prosthesis chip imitates the degenerated photoreceptor cells, senses the incident light and stimulates the remaining healthy layers of retina or optic nerve. Each pixel integrates photodiode and stimulus pulse generator, converting the illumination on the eyes into 3-bit resolution bi-phasic current pulses. On-chip charge cancellation modules are used to discharge each electrode site for tissue safety. The prototype chip is designed and fabricated in 0.18-μm N-well CMOS (complementary metal oxide semiconductor) 1P6M Mix-signal process, with a ±2.5 V dual voltage supply. The functionality of the fabricated chip is demonstrated on anesthetized rabbits. Neural responses in visual cortex are successfully evoked by the neuro-stimulus chip through an on-board trigger interface and flexible electrode.

Anatomy of the ansa cervicalis: Nerve fiber analysis

Ansa cervicalis complex, which innervates the infrahyoid muscles, is formed by the union of two roots derived from the anterior primary rami of the first three or four cervical spinal nerves. According to its relationship with the internal jugular vein, there are three ansa types: medial, lateral, or mixed. Nerve fiber microscopy was carried out in 18 ansa cervicalis complexes after staining with Sudan Black, in order to study composition and structural arrangement in detail. Fibers from both first and second cervical nerves (C1, C2) joined the hypoglossal nerve and later left it partially in the superior root of the ansa, which also contained ascending fibers derived from the inferior root components; usually the second and third cervical nerves. Those ascending fibers, together with the C1 and C2 fibers remaining in the hypoglossal nerve, innervate thyrohyoid and geniohyoid muscles. Cervical nerve fibers could be observed within the hypoglossal nerve even after the ramification of those branches. Further, cervical nerve fibers were continuously issued to the peripheral layers of the hypoglossal nerve where the fibers of the two nerves intermingled, forming a complex structure. The general arrangement of the ansa did not change according to its type or segmental composition. Although the hypoglossal nerve does not make any significant contribution to the formation of the ansa, the close relationship between the two nerves observed in the present study calls for the use of a more descriptive term such as ansa hypoglosso-cervicalis. The pattern of innervation of the infrahyoid muscles is also discussed.

In situ localization of p53, bcl-2 and bax mRNAs in rat ocular tissue

We mapped p53, bcl-2 and bax mRNAs, which are known to have correlation with apoptotic cell death, in the rat ocular tissue. p53 mRNA signals were present in several layers of retina, optic nerve, corneal epithelium, ciliary process and posterior surface of the iris. While almost the same pattern as p53 was recognized in the case of bcl-2 mRNA, bax signals were not found in ocular tissue except for ganglion cell layer (GCL). These results suggest that in the normal ocular tissue, p53 and bcl-2 genes play opposing parts in the physiological control of cell survival and death. A p53 mediated tumor-suppressing action might occur through the induction of transcriptional targets other than bax because only in GCL were p53 and bax mRNA expression co-localized.

Neurotoxic effects of doxycycline sclerotherapy

A patient experienced phrenic nerve paralysis after doxycycline sclerotherapy for treatment of chylous fistula at our institution. The purpose of this study is to use physiologic testing to determine whether doxycycline is capable of inducing defects in neural function. A nonrandomized, controlled trial was performed with nerve-conduction studies to determine possible deleterious effects of doxycycline sclerotherapy. Thirty-eight CD rats were used and separated into four groups. Doxycycline was applied to the sciatic nerves of rats by either topical application directly on the nerve or by intraneural injection. Nerve-conduction studies were done before surgery and at 1, 7, and 21 days after surgery. The results showed a statistically significant decrement in nerve-conduction velocity and strength of transmitted impulse in those nerves injected with doxycycline solution. Complete nerve block was seen frequently. This effect was not seen with topical application of doxycycline or normal saline solution or with intraneural injection of normal saline solution. This study demonstrates that doxycycline can induce a marked decrement in neural function when applied to the subepineural layers of the sciatic nerve in the rat. Therefore doxycycline sclerotherapy should be used with great caution in situations in which it could become exposed to nerves that have sustained surgical trauma. (Otolaryngol Head Neck Surg 1998;118:356-62.)

Neurotic effects of doxycycline sclerotherapy.

A patient experienced phrenic nerve paralysis after doxycycline sclerotherapy for treatment of chylous fistula at our institution. The purpose of this study is to use physiologic testing to determine whether doxycycline is capable of inducing defects in neural function. A nonrandomized, controlled trial was performed with nerve-conduction studies to determine possible deleterious effects of doxycycline sclerotherapy. Thirty-eight CD rats were used and separated into four groups. Doxycycline was applied to the sciatic nerves of rats by either topical application directly on the nerve or by intraneural injection. Nerve-conduction studies were done before surgery and at 1,7, and 21 days after surgery. The results showed a statistically significant decrement in nerve-conduction velocity and strength of transmitted impulse in those nerves injected with doxycycline solution. Complete nerve block was seen frequently. This effect was not seen with topical application of doxycycline or normal saline solution or with intraneural injection of normal saline solution. This study demonstrates that doxycycline can induce a marked decrement in neural function when applied to the subepineural layers of the sciatic nerve in the rat. Therefore doxycycline sclerotherapy should be used with great caution in situations in which it could become exposed to nerves that have sustained surgical trauma.

Microcirculatory bed of the human trigeminal nerve.

The structure and topography of the microcirculatory bed of the human trigeminal nerve are described. Details of microvascular morphology in the epi-, peri-, and endoneurium in different parts of the nerve are emphasized. The vascular bed of the trigeminal nerve was studied following injecting an aqueous solution of black ink and differentiating between microcirculatory components using silver nitrate impregnation. Morphometric parameters were statistically analyzed. Features of vascular organization that control blood flow are found within the pia mater of the trigeminal nerve root coverings, capsule and stroma of the trigeminal ganglion, and the epineurium and external layer of perineurium of extracranial branches. The precapillary arterioles, capillaries, postcapillary venules, and venules are situated in the internal layers of the perineurium. However, while the endoneurium contains only capillaries, the epineurium and external layers of the perineurium contain blood vessels whose features reflect a capability of adapting to a vascular change (transepineural arterioles, arteriolovenular anastomoses, and precapillary sphincters). The inner perineurium layer contains only precapillary sphincters. Results show that the make-up and topography of the microcirculatory bed throughout the trigeminal nerve are determined by features of the connective tissue components. Arteriolovenular anastomoses facilitate blood redistribution within the superficial layers of the trigeminal nerve, while precapillary sphincters and transepineural arterioles provide optimal regulation of blood flow in deeper layers of the nerve trunk.

Is axonal sprouting able to traverse the conjunctival layers of the peripheral nerve? A behavioral, motor, and sensory study of end-to-side nerve anastomosis.

The repair of large peripheral nerve defects is not always possible, especially when the proximal stump is not available. In these cases, end-to-side nerve anastomosis has been proposed. In the present experiment, using the terminal branches of the rat brachial plexus, the authors studied behavioral responses after end-to-side nerve anastomoses using fibrin glue, 3 and 6 months after surgery. Rats were evaluated by results of a grasping test, a capsaicin test and a hot-plate test. The collected data demonstrated that there was no functional motor or sensory reinnervation after the end-to-side nerve anastomoses. The conjunctive layers of the peripheral nerve thus represented an effective barrier to reinnervation.

The Neurotoxic Effects of Doxycycline Sclerotherapy

A patient experienced phrenic nerve paralysis after doxycycline sclerotherapy for treatment of chylous fistula at our institution. The purpose of this study is to use physiologic testing to determine whether doxycycline is capable of inducing defects in neural function. A nonrandomized, controlled trial was performed with nerve-conduction studies to determine possible deleterious effects of doxycycline sclerotherapy. Thirty-eight CD rats were used and separated into four groups. Doxycycline was applied to the sciatic nerves of rats by either topical application directly on the nerve or by intraneural injection. Nerve-conduction studies were done before surgery and at 1,7, and 21 days after surgery. The results showed a statistically significant decrement in nerve-conduction velocity and strength of transmitted impulse in those nerves injected with doxycycline solution. Complete nerve block was seen frequently. This effect was not seen with topical application of doxycycline or normal saline solution or with intraneural injection of normal saline solution. This study demonstrates that doxycycline can induce a marked decrement in neural function when applied to the subepineural layers of the sciatic nerve in the rat. Therefore doxycycline sclerotherapy should be used with great caution in situations in which it could become exposed to nerves that have sustained surgical trauma.

Identification of elastic fibres in the peripheral nerve

Traditional histological staining techniques, as well as elastin-specific antibodies and electron microscopy, have been used to assess the distribution of elastin within the peripheral nerve. The location of the elastin identified by the VerHoeff VanGiesen or Weigert stains has been shown to coincide with the unambiguous identification of elastin by immunospecific stains and electron microscopy. Elastin is located in all three connective layers of the peripheral nerve. Thick elastic fibres, consisting of amorphous elastin protein and microfibrils, are located consistently in the perineurium and, to a lesser extent, in the epineurium. The endoneurium contains small collections of elastic fibres widely distributed between the axons. Compared with collagen, the overall content of elastin, however, is small, suggesting that the visco-elastic properties of peripheral nerve may be due primarily to collagen.

Meningioma of the maxillary sinus.

Extracranial meningiomas are described as being relatively rare, with the majority arising from the meningeal layers of the optic nerve in the orbit.¹ A review of the English literature revealed reports of lesions occurring in the frontal and posterior ethmoid sinuses, but most likely as local extensions from an intracranial source. There has been 1 case only reported of primary meningioma occurring in the maxillary sinus.¹ <h3>Report of a Case</h3> In July, 1961, a 53-year-old white male factory worker consulted the Rhode Island Hospital Ophthalmology Clinic with a 2 year history of progressive, painless obstruction of the right nostril and an 8 month painless, nonpulsatile, outward and upward protrusion of the right eye combined with constant lacrimation. There had been no weight loss, epistaxis, or headache. He noted only occasional episodes of diplopia, but did admit to some recent blurring of vision. Examination revealed proptosis with a visual