Subsequent Nerve Research Articles

Prevalence and risk factors for chronic postamputation pain requiring analgesia or nerve interventions: a population-based study in East Asia

BackgroundPostamputation pain (PAP) is underexplored in East Asian populations, with most data originating from Western countries. This study aimed to investigate the prevalence and risk factors of PAP in East...

Influence of Raoul Husson’s neurochronaxic theory for the development of research on the physiological mechanisms of voice production in the Soviet Union (1950–1970s)

The influence of the neurochronaxic theory of phonation of the French physiologist Raoul Husson (1901–1967) on the development of research on voice formation in the Soviet Union, mainly in the 1950–1970s, is discussed. Husson contrasted the neurochronaxic theory with the traditional myoelastic theory of voice formation. The myoelastic theory considers the vocal folds as a self-oscillatory system. Vibrations are caused by the energy of the air flow. According to Husson’s concept, vibrations of the vocal cords do not depend on subglottic pressure. The frequency of vibration of the vocal cords corresponds to the frequency of impulses arriving along the recurrent nerve. To explain the high frequency of vibration of the vocal cords, Husson used Wever’s “Volley Principle”. According to this principle, the activity of each subsequent nerve fiber occurs during the refractory phase of the previous fiber. The responses of all nerve fibers are summed up into a common high-frequency oscillation. In 1950–1970s, Soviet physiologists took an active part in testing the new concept proposed by Husson. They came to the conclusion that both mechanisms, myoelastic and neurochronaxic, are involved in the functioning of the vocal apparatus. But the recurrent nerve does not directly control the vibrations of the vocal cords, but indirectly. Žhinkin called this control system the “code principle,” when a command is sent to the vocal cords to change their physical characteristics, changing the properties of the self-oscillating system.

Radiologic Clue to Cavernous Sinus Hemangioma Diagnosis

We describe a case of a 57-year-old woman presenting initially with diplopia and later developing retro-orbital and retro-auricular pain. Examination showed right abducens nerve palsy and subsequent right trigeminal nerve hyperesthesia. Neuroimaging revealed a well-defined mass confined to right cavernous sinus, with high T2 signal intensity and homogeneous enhancement on post-gadolinium T1WI. A meningioma was initially considered as the most likely diagnosis. The lesion grew over months, extending to the Meckel's cave and pituitary fossa. Dynamic T1WI revealed striking and progressive centripetal enhancement, leading to a revised diagnosis of cavernous sinus hemangioma (CSH). CSH is a rare benign extra-axial tumor, highly vascularized, frequently misdiagnosed as meningioma or schwannoma. The combination of very high T2 signal intensity and progressive centripetal contrast enhancement highly suggest CSH diagnosis. Given the significant risk of bleeding and mortality associated with surgical intervention, it is crucial to recognize CSH preoperatively to plan a meticulous surgical approach.

Rapid Forming, Robust Adhesive Fungal-Sourced Chitosan Hydrogels Loaded with Deferoxamine for Sutureless Short-Gap Peripheral Nerve Repair.

Clinically, conventional sutures for repair of short-distance nerve injuries (< 5mm) may contribute to uncontrolled inflammation and scar formation, thus negatively impacting nerve regeneration. To repair transected peripheral nerves with short distances, a rapid-forming, robust adhesive chitosan hydrogel is prepared by synthesizing maleic and dopamine bi-functionalized fungal-sourced chitosan (DM) and subsequently photopolymerizing DM precursor solution. The hydrogel rapidly polymerized under UV light irradiation (≈2 s) and possessed a strong adhesive strength (273.33 ± 55.07kPa), facilitating a fast bonding of nerve stump. Especially, its tailored degradation profile over 28 days supported both early gap bridging and subsequent nerve regeneration. Furthermore, deferoxamine (DFO), a pro-angiogenic drug, is loaded into the hydrogel to reach sustainable release, accelerating axonal growth synergistically. A 3mm long sciatic nerve defects model in rats is used to investigate the efficacy of DM@DFO hydrogel for repairing peripheral nerve defects. After 60 days, the DM@DFO hydrogel significantly outperformed conventional sutures and fibrin glue, improving motor and sensory recovery by reducing inflammation, inhibiting scar formation, and accelerating vascular regeneration within 14 days post-repair. This work highlights the DM@DFO hydrogel as a promising tissue adhesive for effective short-distance peripheral nerve repair.

The transcriptional landscape of the developing chick trigeminal ganglion.

The trigeminal ganglion is a critical structure in the peripheral nervous system, responsible for transmitting sensations of touch, pain, and temperature from craniofacial regions to the brain. Trigeminal ganglion development depends upon intrinsic cellular programming as well as extrinsic signals exchanged by diverse cell populations. With its complex anatomy and dual cellular origin from cranial placodes and neural crest cells, the trigeminal ganglion offers a rich context for examining diverse biological processes, including cell migration, fate determination, adhesion, and axon guidance. Avian models have, so far, enabled key insights into craniofacial and peripheral nervous system development. Yet, the molecular mechanisms driving trigeminal ganglion formation and subsequent nerve growth remain elusive. In this study, we performed RNA-sequencing at multiple stages of chick trigeminal ganglion development and generated a novel transcriptomic dataset that has been curated to illustrate temporally dynamic gene expression patterns. This publicly available resource identifies major pathways involved in trigeminal gangliogenesis, particularly with respect to the condensation and maturation of placode-derived neurons, thus inviting new lines of research into the essential processes governing trigeminal ganglion development.

Metabolic Dysfunction in New-Onset Idiopathic Intracranial Hypertension: Identification of Novel Biomarkers.

Idiopathic intracranial hypertension (IIH) is a neurometabolic disease with an increasing incidence. The pathophysiology is unknown, but improvement of diagnosis and management requires discovery of novel biomarkers. Our objective was to identify such candidate biomarkers in IIH, and secondarily, test for associations between identified metabolites and disease severity. This is a prospective case-control study with collection of cerebrospinal fluid (CSF), serum, and clinical data from new-onset, treatment-naïve patients with IIH (n = 60). Patients were included consecutively from 2 tertiary headache centers in Denmark, and age, sex, and body mass index (BMI) -matched healthy controls (n = 35) were recruited. Clinical data were retrieved at ocular remission (n = 55). Samples were analyzed using non-targeted mass spectrometry. Serum sphingosine 1-phosphate (S1P), adenosine, and glutamate were 0.46-fold (q < 0.0001), 0.25-fold (q = 0.0048), and 0.44-fold (q < 0.0001) lower, respectively, in IIH. CSF stearoyl-lysophosphatidylcholine (LysoPC-18) and 2-palmitoyl-lysophosphatidylcholine (LysoPC-16) were 0.42 (q = 0.0025) and 0.37 (q < 0.001) -fold lower. LysoPC-18 was higher in patients with moderate-severe versus mild papilledema (p = 0.022). LysoPC-18 correlated positively with retinal nerve fiber layer thickness (p = 0.0012, r = 0.42) and inversely with mean deviation on automated perimetry (p = 0.01, r = -0.35). Higher baseline serum S1P (p = 0.018) and lower CSF LysoPC-16 (p = 0.003) were associated with optic nerve atrophy at ocular remission. Pathway analysis suggests dysregulated lipid metabolism and redox disturbances in new-onset IIH. We identify perturbed metabolism in new-onset IIH. S1P and LysoPC-16 demonstrate potential prognostic value due to association with subsequent optic nerve atrophy. This association between specific, differential metabolites and outcome provides substantial evidence for novel biomarkers of clinical significance that should be the focus of further targeted studies. ANN NEUROL 2024;96:595-607.

Case report: Focal heterotopic ossification in paravertebral muscles as a cause of neurogenic lameness in a dog

This case report describes a 17-month-old Pudelpointer with recurring motor impairment localized to the left thoracic limb. A neurological exam highlighted lameness in that limb, accompanied by pre-scapular swelling. Radiographs and magnetic resonance imaging detected an osseous structure in soft tissues close to the fifth cervical vertebra, and subsequent surgery uncovered adjacent cervical spinal nerve impingement. Histology of the bony structure revealed heterotopic ossification in paravertebral muscles. Mild bone re-formation at the operating site was detected after a 2-year period, but the patient was asymptomatic. This article reports the first case of heterotopic ossification with spinal nerve entrapment in a dog and adds a new differential diagnosis to the causes of neurogenic lameness in dogs.

Visual dysfunction and neurodegeneration caused by severe inflammatory optic neuropathy after coil embolization of a paraclinoid aneurysm: illustrative case.

Visual impairment due to delayed optic neuropathy is a rare complication of the endovascular treatment of paraclinoid aneurysms. An inflammatory response induced in the treated aneurysm wall is a known mechanism underlying this pathophysiology. The authors describe a case with severe and progressive optic neuropathy leading to neuronal degeneration and severe visual dysfunction. A 42-year-old female with a history of surgical clipping for a paraclinoid aneurysm presented with a recurrence. Although the patient was unaware of any visual dysfunction, a preoperative ophthalmological examination revealed mild inferior quadrantanopia in the left eye. The coil embolization procedure was uneventful; however, the following day, the patient experienced progressive visual impairment, which worsened despite the initiation of steroid therapy. Ophthalmological examination revealed a severe decrease in visual acuity and further deterioration of the visual field. Magnetic resonance imaging showed remarkable swelling and edema of the left optic nerve adjacent to the treated aneurysm. Despite continued steroid therapy, the patient's visual function did not recover well due to subsequent optic nerve degeneration. Optic neuropathy after endovascular procedures can lead to severe visual dysfunction. Careful management is essential, particularly when treating a symptomatic paraclinoid aneurysm, even if symptoms are only apparent on detailed examination.

The Potential and Application of iPSCs in Gene and Cell Therapy for Retinopathies and Optic Neuropathies.

This review focuses on in vitro modeling of diseases and the development of therapeutic strategies using iPSCs for the two most common types of optical pathologies: hereditary neuropathies and retinopathies. Degeneration of retinal ganglion cells and the subsequent optic nerve atrophy leads to various types of neuropathies. Damage to photoreceptor cells or retinal pigment epithelium cells causes various retinopathies. Human iPSCs can be used as a model for studying the pathological foundations of diseases and for developing therapies to restore visual function. In recent years, significant progress has also been made in creating ganglionic and retinal organoids from iPSCs. Different research groups have published data pertaining to the potential of using iPSCs for the modeling of optic neuropathies such as glaucoma, Leber hereditary optic neuropathy, etc., including in the development of therapeutic approaches using gene editing tools.

Plasmacytoid dendritic cell‐derived secretome ameliorates neuropathic corneal pain

Aims/Purpose: Prior work from our group has demonstrated a role for plasmacytoid dendritic cells (pDCs) in corneal nerve homeostasis. Herein, we sought to determine if pDC‐derived secretome could be used for the treatment of neuropathic corneal pain.Methods: The BDCA2‐DTR transgenic mice, in which pDCs can be selectively depleted result in subsequent nerve degeneration, were utilized for ex vivo electrophysiology studies. Animals were treated with pDC secretome drops, beginning 1 day after initial depletion. Electrophysiologic recordings were taken at day 3 post‐depletion analysed. A ciliary nerve ligation model of neuropathic corneal pain (NCP), was used to assess the therapeutic potential of pDC secretome. Spontaneous and evoked pain responses were assessed by palpebral opening measurements and hyperosmolar saline, respectively.Results: There was a significant reduction in cooling threshold following pDC depletion, which was rescued by pDC secretome treatment (26.85 ± 0.65°C vs. 29.52 ± 0.42°C; p &lt; 0.05), restoring the cooling threshold to control levels (29.21 ± 0.51). Furthermore, nerve terminal exhaustion was reduced following pDC depletion and rescued by pDC secretome treatment (0.55 ± 0.08 vs. 1.11 ± 0.10; p &lt; 0.01). Spontaneous pain responses were worse in the vehicle‐treated compared to pDC secretome‐treated group (0.67 ± 0.03 vs. 0.85 ± 0.02; p &lt; 0.001). Similarly, evoked pain responses were worse in the vehicle‐treated compared to pDC secretome‐treated group (30.25 ± 1.50 wipes/30 sec vs. 15.38 ± 1.29; p &lt; 0.0001).Conclusions: Herein, we demonstrate that pDC secretome restores normal functioning of corneal cold receptors. Importantly, in a translational model of NCP, pDC secretome treatment improved both spontaneous and evoked pain responses. Thus, pDC secretome is a viable therapeutic modality for further development and may hold promise in treatment of NCP and other corneal nerve related diseases.Reference1. Jamali A, Kenyon B, Ortiz G, Abou‐Slaybi A, Sendra VG, Harris DL, Hamrah P. Plasmacytoid Dendritic Cells in the Eye. Prog Retin Eye Res 2021; 80: 100877.2. Jamali A, Hu K, Sendra VG, Blanco T, Qazi Y, Zheng L, Turhan A, Hamrah P. Characterization of Resident Corneal Plasmacytoid Dendritic Cells and Their Pivotal Role in Herpes Simplex Keratitis. Cell Rep 2020; 32: 108099.

UNILATERAL PAPILLEDEMA DUE TO IDIOPATHIC INTRACRANIAL HYPERTENSION: A CASE REPORT

Introduction: Papilledema is highly predicted and common to encounter in all causes of raised intracranial pressure including idiopathic intracranial hypertension; it is usually bilateral and symmetrical. Unilateral and asymmetrical papilledema is considered highly atypical and a rarity of presentation, posing significant diagnostic challenge to the poorly understood pathological phenomenon of IIH.Case: We report a 40-year-old African female with idiopathic intracranial hypertension who fully fulfills the Modified Danddy Criteria; presenting with unilateral papilledema, with Left eye fundoscopic examination showing extensively hyperemic and swollen optic disc with an associated tortuously engorged retinal vein. Brain imaging via MRI revealed partial empty sella, bilateral prominent fluid signal projection that is more evident in the left optic nerve sheath and a prominent meckel’s cave on the left side measuring (6.1 mm) in the transverse diameter. MRA concluded an attenuated most lateral side of the left transverse sinus. Lumbar puncture was attempted and revealed an opening pressure of (45 cmH2O), and otherwise normal CSF cytology and chemical composition. Significant symptomatic relief was depicted upon lumbar puncture.Discussion: papilledema is universally encountered as a bilateral and symmetrical phenomenon; thus, presentation of IIH with unilateral papilledema has been under extensive research recently in attempts to contemplate the exact pathophysiology. Amongst many other proposed theories, we endorse the variation of the optic canal diameter as a potential mechanism for asymmetry of papilledema in IIH. As larger optic canal diameter is postulated to be associated with higher CSF pressure force transduction with subsequent optic nerve damage.Conclusion: Unilateral and asymmetrical papilledema is considered substantially unique and anecdotal rarities of presentation of IIH; posing a significant diagnostic troublesome and dilemma. Physicians should be aware and highly vigilant of such deviations of usual presentations to avoid consequential diagnostic and management adverse outcomes and unwanted complications.

Proliferative diabetic retinopathy as the initial presenting feature of type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder caused by the destruction of the pancreatic beta cells, which produce insulin. Individuals with T1DM usually require at least 3-5 years to develop microvascular complications in comparison to people with type 2 diabetes (T2DM), who may develop complications even before the diagnosis of diabetes. We discuss a patient who presented with proliferative diabetic retinopathy subsequently diagnosed with T1DM and diabetic neuropathy following investigations. Diabetic retinopathy or other microvascular complications as the presenting feature of T1DM is rarely known or reported in the literature. A 33-year-old healthcare worker had been seen by the opticians due to 1-week history of blurred vision. The ophthalmology assessment had confirmed proliferative retinopathy in the right eye and severe non-proliferative retinopathy in the left eye with bilateral clinically significant macular oedema. His BMI was 24.9 kg/m2. The nervous system examination revealed bilateral stocking type peripheral neuropathy. The random venous glucose was 24.9 mmol/L. Plasma ketones were 0.7 mmol/L and HbA1c was 137 mmol/mol. On further evaluation, the anti-glutamic acid decarboxylase (GAD) antibody was positive, confirming the diagnosis of T1DM. He was started on aflibercept injections in both eyes, followed by panretinal photocoagulation. Subsequent nerve conduction studies confirmed the presence of symmetrical polyneuropathy. The pathogenesis of the development of microvascular complications in T1DM is multifactorial. Usually, the development of complications is seen at least a few years following the diagnosis. The occurrence of microvascular complications at presentation is rare. This makes the management challenging and extremely important in preventing the progression of the disease. The pathogenesis of the development of microvascular complications in type 1 diabetes mellitus is multifactorial. The development of complications is seen at least a few years following the diagnosis. Occurrence of microvascular complications at presentation is rare. This makes the management challenging and extremely important to prevent the progression of the disease.

Effects of Novel Dual Peripheral Nerve Stimulator Therapy: A Case Report

BACKGROUND: Peripheral nerve stimulators (PNS) are currently used for refractory cases of neuralgia, and are associated with single manufacturer use. This is the first case report describing the novel scenario where a patient received 2 neuromodulation devices from 2 different manufacturers. CASE REPORT: We present a 32-year-old woman with spinal muscle atrophy type 2 who received a permanent PNS implant for chronic neuralgia. She experienced gradual treatment failure over 6 months, but continued to have pain relief with subsequent nerve blocks to the same nerves. She underwent semipermanent PNS placement to those same nerves. After the semipermanent PNS was removed, she experienced new, unexpected symptoms after trying to use her permanent PNS again. CONCLUSION: Instances of multiple PNS treating the same area in patients is likely going to be a recurring scenario. More research will be needed to document the potential effects that dual neuromodulation therapy may have. KEY WORDS: Case report, chronic pain, dual therapy, peripheral nerve stimulator

The Double-Opposing Adipofascial Interposition Flap: A Novel Technique to Prevent Scar Tethering and Symptomatic Neuroma of the Superficial Radial Nerve After Trauma.

The superficial radial nerve (SRN) is vulnerable to injury following trauma with a high incidence of resultant nerve tether and neuroma formation. The SRN has an anatomical predisposition to neuroma formation, with research indicating that its propensity to neuroma development is out of proportion with its likelihood for injury. In addition, SRN neuromas havebeen described as one of the more painful and difficult neuromas to manage. Despite this, the published literature to date is chiefly focused on neuroma and scar tether treatment options rather than more impactful work on neuroma prevention, which can be safely delivered at the time of primary surgery. Treatment of established neuroma or nerve tether is notoriously difficult, and existing techniques have inconsistent outcomes, with patients often requiring multiple trips to the theatre. The authors present a novel technique for neuroma and scar tether prevention using an adipofascial flap accompanied by patient examples of our experience using this approach as an adjunct during the primary SRN repair, creating a gliding, interposing layer to prevent subsequent nerve traction pain and symptomatic neuroma. We identified five patients presenting with dorsal wrist injuries involving the SRN and one or more tendons. Patients' follow-up duration was a mean of 3.5 months (one to eight months). All follow-up patients showed no symptoms of a neuroma or nerve tether pain. All patients were discharged without re-referral or further surgery. Our patient sample demonstrates promising results using an adipofascial interposition flap as a prophylactic measure in traumatic injuries to reduce nerve tether pain and symptomatic neuroma formation in the SRN.

Incidence and Etiology of Rare Saphenous Nerve Injury After Knee Surgery with Adductor Canal Block: A Retrospective Observational Study.

Adductor canal block (ACB) is commonly included in multimodal analgesia regimens for knee surgery. Nonetheless, the incidence, etiology, and procedure-specific risk of saphenous nerve injury after knee surgery with ACB have not been established. We sought to identify the risk of saphenous nerve injury during knee surgery with ACB. We conducted a retrospective cohort study of patients at a single institution who underwent elective knee surgery with ultrasound-guided ACB between January 1, 2014, and December 31, 2018, and had subsequent saphenous nerve injury. The primary outcome was the incidence of saphenous nerve injury within 3 months of surgery, by surgical type and approach. Secondary outcomes included attribution of the most likely etiology and clinical outcome of the injury. In 28,196 cases of knee surgery with ACB, we identified 18 cases (0.06%) of saphenous nerve injury. The most common surgery associated with saphenous nerve injury was anterior cruciate ligament (ACL) reconstruction with autograft (8/18 cases); 3 cases of injury were seen after TKA, 2 after medial patellofemoral ligament reconstruction, 2 after arthroscopy/meniscal surgery, and 1 after patellar fixation. The most likely etiology of nerve injury was attributed to ACB in 5 of 18 cases (28%) and to non-ACB cause in 13 of 18 (72%). Prognosis was rated as unknown in 11 of 18, poor in 2 of 18, favorable in 3 of 18, and full recovery in 2 of 18. This 5-year retrospective, single-institution cohort study found a low overall incidence of saphenous nerve injury after knee surgery with ACB, but the injury likelihood varied based on surgery and approach. Although not statistically significant, ACL reconstruction with hamstring autograft and ACB performed for postoperative rescue analgesia were most frequently associated with nerve injury.

Surgery for internal rotation contracture in infancy may obviate the need for brachial plexus nerve reconstruction: early experience

Shoulder internal rotation contracture and subluxation in the first year of life has long been recognized in some patients with brachial plexus birth injury (BPBI). Surgical management of shoulder pathology has traditionally been undertaken following nerve reconstruction as necessary. In some patients, however, shoulder pathology may impair or obscure functional neuromuscular recovery of the upper extremity. As a proof of concept, we report a highly selected subset of patients with BPBI in whom shoulder surgery undertaken before one year of age obviated the need for neuroma resection and nerve grafting. A retrospective review was performed of all patients with upper trunk BPBI who underwent shoulder surgery before one year of age from 2015 to 2018. Upper extremity motor function was evaluated with preoperative and postoperative Active Movement Scale (AMS) scores, Cookie Tests, and the requirement for subsequent neuroma resection and nerve grafting. Fifteen patients with BPBI meeting the inclusion criteria underwent shoulder surgery (including a subscapularis slide and tendon transfers of the teres major and latissimus dorsi muscles) before 1 year of age. Preoperatively, no patients of the appropriate age passed the Cookie Test for elbow flexion. Thirteen patients either passed the Cookie Test or scored AMS 7 for elbow flexion at or before the last available follow-up undertaken at a median age of 3.4 [1.4, 5.2] years. One of those 13 patients underwent single fascicular distal nerve transfer to improve elbow flexion before subsequently passing the Cookie Test. Two patients did not have sufficient follow to assess elbow flexion. Although the exact role of shoulder surgery in infancy for BPBI remains to be defined, the findings from this study provide proof of concept that early, targeted surgical treatment of the shoulder may obviate the need for brachial plexus nerve reconstruction in a highly selected group of infants with BPBI.

Supramolecular assemblies with spatio-temporal sequential drug delivery capability treat spinal cord injury via neuroprotection and immunoregulation

Spinal cord injury (SCI) can result in irreversible motor and sensory deficits. However, up to data, clinical first-line drugs have ambiguous benefits and debilitating side effects, mainly due to the insufficient accumulation, poor physiological barrier penetration, and lack of spatio-temporal controlled release at lesion tissue. Herein, we proposed a supramolecular assemblies composed of hyperbranched polymer-formed core/shell structure through host-guest interactions. Such HPAA-BM@CD-HPG-C assemblies co-loaded with p38 inhibitor (SB203580) and insulin-like growth factor 1(IGF-1) are able to achieve time- and space-programmed sequential delivery benefiting from their cascaded responsiveness. The core-shell disassembly of HPAA-BM@CD-HPG-C occurs in acidic micro-environment around lesion, achieving preferentially the burst release of IGF-1 to protect survival neurons. Subsequently, the HPAA-BM cores containing SB203580 are endocytosed by the recruited macrophages and degraded by intracellular GSH, accelerating the release of SB203580 to promote the conversion from M1 to M2 macrophage. Hence, the successive synergy of neuroprotection and immunoregulation effects contribute to subsequent nerve repair and locomotor recovery as demonstrated in vitro and in vivo studies. Thus, our fabrication provides a strategy that multiple drugs co-delivery in a spatio-temporal selective manner adapting to the disease progression through self-cascaded disintegration, are expected to realize multidimensional precise treatment of SCI.

Perspectives on Adherence to Glaucoma Medical Therapy in Brazilian Patients.

Poor adherence to glaucoma medication regimens may be associated with subsequent optic nerve damage and irreversible visual loss. Specific barriers to effective patient adherence in low-middle income countries are not fully recognized and new disease-specific instruments to assess adherence have been developed. The purpose of this cross-sectional study was to evaluate adherence of primary open-angle glaucoma (POAG) patients to treatment in a middle-income country. POAG patients were recruited from the Glaucoma Service - Irmandade da Santa Casa de Misericordia de Sao Paulo, Sao Paulo, Brazil. Clinical and demographic data were retrieved from participants' electronic records. All patients answered the Glaucoma Treatment Compliance Assessment Tool (GTCAT). This 27-item questionnaire was designed to evaluate multiple behavioral factors associated with glaucoma medication adherence. The sample comprised 96 patients with POAG. The mean age was 63.2 ± 8.9 years; 48 were male and 48 female; 55 (57.3%) were White, 36 (37.5%) African-Brazilian, and five (5.2 %) were of mixed color. Most patients (97.9%) had less than a high school degree and all had a family income <US$10,000. The GTCAT identified 69 (71.8%) patients who "sometimes forget to use drops," 68 (70.8%) patients who "sometimes fall asleep before dosing time," and 60 (62.5%) patients "whose drops aren't with them at the time to take them"; 82 (85.4%) patients admitted to using "reminders to take medications." Eighty-two (85.4%) patients agreed that "doctor answers my questions," and 77 (80.5%) said "they are happy with their eye doctor." The GTCAT identified a number of mostly unintentional factors associated with adherence in this cohort of Brazilian patients. The data may impact on how to understand and improve adherence to ocular hypotensive treatment in the Brazilian population.

Spinal muscular atrophy with hypoplasia of the corpus callosum: a case report

BackgroundSpinal Muscular Atrophy (SMA) is a severe neuromuscular disorder due to a defect in the survival motor neuron 1 (SMN1) gene. Hypoplasia of the corpus callosum is underdevelopment or thinness of the corpus callosum. SMA and callosal hypoplasia are relatively rare, and there is limited information sharing the diagnosis and treatment for SMA patients with callosal hypoplasia.Case descriptionA boy with callosal hypoplasia, small penis, and small testes had been perceived with motor regression at 5 months. He was referred to the rehabilitation department and neurology department at 7 months. Physical examination showed absent deep tendon reflexes, proximal weakness and significant hypotonia. He was recommended to perform trio whole-exome sequencing (WES) and array comparative genomic hybridization (aCGH) for his complicated conditions. The subsequent nerve conduction study revealed some characteristics of motor neuron diseases. We identified a homozygous deletion in exon 7 of the SMN1 gene by multiplex ligation-dependent probe amplification and failed to find further pathogenic variations responsible for multiple malformations by trio WES and aCGH. He was diagnosed as SMA. Despite some concerns, he received the therapy of nusinersen for nearly 2 years. He gained the milestone of sitting without support, which he had never accomplished, after the seventh injection, and he continued to improve. During follow-up, there were no adverse events reported and no signs of hydrocephalus.ConclusionsSome extra features which could not belong to neuromuscular manifestation made the diagnosis and treatment of SMA more complicated.

Heterogeneous pHPMA hydrogel promotes neuronal differentiation of bone marrow derived stromal cells in vitro and in vivo

Synthetic hydrogels composed of polymer pore frames are commonly used in medicine, from pharmacologically targeted drug delivery to the creation of bioengineering constructions used in implantation surgery. Among various possible materials, the most common are poly-[N(2-hydroxypropyl)methacrylamide] (pHPMA) derivatives. One of the pHPMA derivatives is biocompatible hydrogel, NeuroGel. Upon contact with nervous tissue, the NeuroGel’s structure can support the chemical and physiological conditions of the tissue necessary for the growth of native cells. Owing to the different pore diameters in the hydrogel, not only macromolecules, but also cells can migrate. This study evaluated the differentiation of bone marrow stromal cells (BMSCs) into neurons, as well as the effectiveness of using this biofabricated system in spinal cord injury in vivo. The hydrogel was populated with BMSCs by injection or rehydration. After cultivation, these fragments (hydrogel + BMSCs) were implanted into the injured rat spinal cord. Fragments were immunostained before implantation and seven months after implantation. During cultivation with the hydrogel, both variants (injection/rehydration) of the BMSCs culture retained their viability and demonstrated a significant number of Ki-67-positive cells, indicating the preservation of their proliferative activity. In hydrogel fragments, BMSCs also maintained their viability during the period of cocultivation and were Ki-67-positive, but in significantly fewer numbers than in the cell culture. In addition, in fragments of hydrogel with grafted BMSCs, both by the injection or rehydration versions, we observed a significant number up to 57%–63.5% of NeuN-positive cells. These results suggest that the heterogeneous pHPMA hydrogel promotes neuronal differentiation of bone marrow-derived stromal cells. Furthermore, these data demonstrate the possible use of NeuroGel implants with grafted BMSCs for implantation into damaged areas of the spinal cord, with subsequent nerve fiber germination, nerve cell regeneration, and damaged segment restoration.