Corneal neurotization: a narrative review of techniques, outcomes, and surgical considerations

Background and Objective:Corneal neurotization is a novel surgical technique used to restore corneal sensation in patients with neurotrophic keratopathy.Neurotrophic keratopathy is a disorder characterized by dysfunction of the ophthalmic division of the trigeminal nerve,which provides sensory innervation to the cornea.Without sensation,the cornea is at risk of infection,ulceration,perforation,and ultimately,vision loss.Corneal neurotization has emerged as an innovative technique to reinnervate anesthetized corneas by transferring a healthy donor nerve to the affected eye around the corneoscleral limbus.As the field of corneal neurotization rapidly grows,there is a need to synthesize the existing body of literature on corneal neurotization and identify important areas for further research.In this review,we will discuss neurotrophic keratopathy and its current management strategies,followed by an overview of corneal neurotization techniques,outcomes,surgical considerations,and future directions.Methods:PubMed and Google Scholar searches were conducted to retrieve and analyze relevant original papers and reviews on neurotrophic keratopathy and corneal neurotization up until April 2022.Key Content and Findings:Currently,numerous techniques for corneal neurotization exist,including direct nerve transfers,as well as indirect neurotization via interposition nerve grafts.So far,corneal neurotization has been shown to be highly successful in restoring corneal sensation,improving visual acuity,and improving corneal epithelial health.To date,there have been no significant differences in outcomes between direct versus indirect neurotization techniques,different donor nerves,or autologous versus allogeneic interposition grafts.However,there is some evidence that corneal neurotization procedures may be more successful in pediatric patients.Conclusions:Corneal neurotization shows great promise in treating neurotrophic corneas and represents the first management option to date that addresses the underlying pathophysiological mechanism of neurotrophic keratopathy by restoring corneal sensation.As the use of corneal neurotization continues to broaden,additional studies will become important to compare techniques in a systematic manner,with larger sample sizes,as well as standardized outcome measures and follow-up time.

Herpes simplex keratitis:A brief clinical overview

The aim of our minireview is to provide a brief overview of the diagnosis,clinical aspects,treatment options,management,and current literature available regarding herpes simplex keratitis(HSK).This type of corneal viral infection is caused by the herpes simplex virus(HSV),which can affect several tissues,including the cornea.One significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the cornea.After the initial infection,the HSV can establish a latent infection in the trigeminal ganglion,a nerve cluster near the eye.The virus may remain dormant for extended periods.Periodic reactivation of the virus can occur,leading to recurrent episodes of HSK.Factors triggering reactivation include stress,illness,immunosuppression,or trauma.Recurrent episodes can manifest in different clinical patterns,ranging from mild epithelial involvement to more severe stromal or endothelial disease.The severity and frequency of recurrences vary among individuals.Severe cases of HSK,especially those involving the stroma and leading to scarring,can result in vision impairment or even blindness in extreme cases.The cornea's clarity is crucial for good vision,and scarring can compromise this,potentially leading to visual impairment.The management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via neurotization.Antiviral medications,such as oral Acyclovir or topical Ganciclovir,may be prescribed for prophylaxis.The immune response to the virus can contribute to corneal damage.Inflammation,caused by the body's attempt to control the infection,may inadvertently harm the corneal tissues.Clinicians should be informed about triggers and advised on measures to minimize the risk of reactivation.In summary,the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintain optimal visual function.

Neurotization of oculomotor,trochlear and abducent nerves in skull base surgery

Objective To anatomically reconstruct the oculomotor nerve, trochlear nerve, and abducent nerve by skull base surgery. Methods Seventeen cranial nerves (three oculomotor nerves, eight trochlear nerves and six abducent nerves) were injured and anatomically reconstructed in thirteen skull base operations during a period from 1994 to 2000. Repair techniques included end-to-end neurosuture or fibrin glue adhesion, graft neurosuture or fibrin glue adhesion. The relationships between repair techniques and functional recovery and the related factors were analyzed.Results Functional recovery began from 3 to 8 months after surgery. During a follow-up period of 4 months to 6 years, complete recovery of function was observed in 6 trochlear nerves (75%) and 4 abducent nerves (67%), while partial functional recovery was observed in the other cranial nerves including 2 trochlear nerves, 2 abducent nerves, and 3 oculomotor nerves.Conclusions Complete or partial functional recovery could be expected after anatomical neurotization of an injured oculomotor, trochlear or abducent nerve. Our study demonstrated that, in terms of functional recovery, trochlear and abducent nerves are more responsive than oculomotor nerves, and that end-to-end reconstruction is more efficient than graft reconstruction. These results encourage us to perform reconstruction for a separated cranial nerve as often as possible during skull base surgery.

L4-to-L4 nerve root transfer for hindlimb hemiplegia after hypertensive intracerebral hemorrhage

There is no effective treatment for hemiplegia after hypertensive intracerebral hemorrhage.Considering that the branches of L4 nerve roots in the lumbar plexus root control the movement of the lower extremity anterior and posterior muscles,we investigated a potential method of nerve repair using the L4 nerve roots.Rat models of hindlimb hemiplegia after a hypertensive intracerebral hemorrhage were established by injecting autogenous blood into the posterior limb of internal capsule.The L4 nerve root on the healthy side of model rats was transferred and then anastomosed with the L4 nerve root on the affected side to drive the extensor and flexor muscles of the hindlimbs.We investigated whether this method can restore the flexible movement of the hindlimbs of paralyzed rats after hypertensive intracerebral hemorrhage.In a beam-walking test and ladder rung walking task,model rats exhibited an initial high number of slips,but improved in accuracy on the paretic side over time.At 17 weeks after surgery,rats gained approximately 58.2%accuracy from baseline performance and performed ankle motions on the paretic side.At 9 weeks after surgery,a retrograde tracing test showed a large number of fluoro-gold-labeled motoneurons in the left anterior horn of the spinal cord that supports the L4-to-L4 nerve roots.In addition,histological and ultramicrostructural findings showed axon regeneration of motoneurons in the anterior horn of the spinal cord.Electromyography and paw print analysis showed that denervated hindlimb muscles regained reliable innervation and walking coordination improved.These findings suggest that the L4-to-L4 nerve root transfer method for the treatment of hindlimb hemiplegia after hypertensive intracerebral hemorrhage can improve the locomotion of hindlimb major joints,particularly of the distal ankle.Findings from study support that the L4-to-L4 nerve root transfer method can effectively repair the hindlimb hemiplegia after hypertensive intracerebral hemorrhage.All animal experiments were approved by the Animal Ethics Committee of the First Affiliated Hospital of Nanjing Medical University(No.IACUC-1906009)in June 2019.

Forty Cases of Gastrointestinal Neurosis Treated by Acupunture

Objective： To compare the therapeutic effect of acupuncture for gastrointestinal neurosis with that of oral remedy. Methods： Eighty cases were randomly divided into the following 2 groups. In the treatment group, acupuncture was given for one month at the main points of Zhongwan （CV 12）, Zusanli （ST 36）, Taichong （LR 3） and Shenmen （HT 7）, with the auxiliary points selected according to TCM differentiation. In the control group, Domperidone was orally administered for one month. Results： The total effective rate was 92.5% in the treatment group and 75.0% in the control group, with a significant difference between the 2 groups 0（2=4.423, P〈0.05）. Acupuncture was superior to the oral remedy in therapeutic effects. Conclusions： Acupuncture may show better results for gastrointestinal neurosis and with less toxic side effects.

The Major Psychocutaneous Disorders in Iraqi Patients

Background: Many skin diseases can be evoked by psychological problems. Dermatological conditions could also lead to psychological disorders;hence psychodermatology is an emerging subspecialty that focuses on the interface of psychiatry and dermatology. Objective: To assess the frequency of the major disorders of so-called psychocutaneous disorders which are commonly seen among Iraqi population. Patients and Methods: This case descriptive study had been done in Department of Dermatology-Baghdad Teaching Hospital, Medical City, Baghdad, Iraq during the period from March 2011 to October 2013. All cases were collected and categorized according to the disease problem. Patients were interviewed to search for the main triggering and precipitating factors involved in pathogenesis of these disorders. The clinical picture was well described in order to reach a final diagnosis. Psychological interview and analysis were performed for all patients to reach the specific emotional and psychiatric disease by consultant psychiatrist. Results: A total of 100 patients with major psychocutaneous disorders were seen and evaluated. Nineteen were males and 81 were females with female to male ratio: 4.26:1. Their ages ranged from 7 - 73 (26.5 ± 5.217) years. The frequency of these diseases was as follows: trichotillomania 53%, dermatitis artifacta 37%, delusion of parasitosis 6% and neurotic excoriation 4%. Conclusions: The major psychocutaneous diseases in Iraqi population were: trichotillomania, dermatitis artifacta and these are problems of mainly young females while delusion of parasitosis and neurotic excoriations were diseases of middle age females.

About a Case of Neurotic Angioedema Induced by Angiotensin Converting Enzyme Inhibitor

Neurotic angioedema may be secondary to ACE (Angiotensin-converting enzyme) inhibitor. From a case of neurotic angioedema in a hypertensive man under ACE (Angiotensin-converting enzyme) inhibitor, we expose the clinical characteristics typical of the edema and its evolution. A 73-year-old man has consulted for edema of the face and redness of the palmar surface of the hand not pruriginous for 2 days. He has already had conventional anti-edematous treatments but no changes. In the absence of a technical platform, no paraclinical examination was carried out. The cessation of ACE inhibitor and the administration of tranexamic acid were made immediately. Signs regressed within 24 hours. Neurotic angioedema is a diagnostic problem in countries where biological examination is still limited and if practitioners are unaware of the possibility of its occurrence during IEC treatment. While the patient’s prognosis depends on the precocity of management.

300 CASES OF MENOPAUSAL SYNDROME TREATED BY ACUPUNCTURE

Caused by hypo-ovarianism, menopausal syndrome usually occurs in women aged from 45-55 years. With high incidence and various symptoms, the disease often severely jeopardize the health of the women. The authors had treated 300 cases of menopausal syndrome by acupuncture and obtained a good result.

A multifunctional neuromodulation platform utilizing Schwann cell-derived exosomes orchestrates bone microenvironment via immunomodulation, angiogenesis and osteogenesis

Recent evidence highlights multifaceted biological needs to recapitulate the bone microenvironment for bone regeneration.Neurotization has great potential for realizing multi-system modulations in bone tissue engineering(BTE).However,a neural strategy involving all the key bone repair steps temporally has not yet been reported.In this study,we reported the neural tissue engineering hydrogel-encapsulated Schwann cell-derived exosomes(SC Exo).This sustained-release SC Exo system prominently enhanced bone regeneration by promoting innervation,immunoregulation,vascularization,and osteogenesis in vivo.Moreover,the in vitro results further confirmed that this system significantly induced M2 polarization of macrophages,tube formation of HUVECs,and BMSCs osteogenic differentiation.Furthermore,BMSCs osteogenesis was promoted by upregulating the TGF-β1/SMAD2/3 signaling pathway.In summary,a novel cell-free and easily prepared SC Exo neural engineering was successfully developed to promote bone regeneration by orchestrating the entire bone healing microenvironment,which may provide a new strategy for tissue engineering and clinical treatment of bone defects.

The role of peripheral nerve surgery in a tissue reinnervation

In modern neuroscience,the most relevant is the study of the problem of reinnervation of tissues after severe injuries.Complete restoration of lost physiological functions is still impossible with lesions of peripheral nerves with the formation of extensive diastasis between their proximal and distal sites.In this case,the standard neurorrhaphy cannot be carried out because of the eruption of the filaments during tension and convergence of the ends.To solve this problem,a technique was developed for autotransplantation of the nerve sections,which is still the gold standard for the reconstruction of extensive nerve defects.However,the presence of significant shortcomings led to the development of the doctrine of the direction of regeneration with the help of conduits.Currently,the use of nerve channels is the most promising technology for peripheral nerve repair after trauma.The most actively developing now is the direction of reinnervation,such as neurotization.Neurotization,in some way,combined all the methods of restoring nerves.The overall goal of all these methods—the restoration of extensive nerve defects—allows them to be combined into a new industry:reinnervating neurosurgery.

Reality Through Insanity——A Survey of the Neurotic Heroes in American Novels of the 1960s (Continued)

Norman Mailer has made a profound analysisof the mad logic of the Vietnam war in his Armiesof the Night, a novel of new journalism whichconcludes the schizophrenic environment of Ameri-can society is at the root of this lunatic war: "He (Norman Mailer) came at last to the saddest conclusion ... that the centre of America might be insane. The country had been living with a controlled, even fiercely controlled, schizophrenia which had been deepening with the years. Perhaps the point had now been passed." (AN. 188)Traditional Christianity as a unifying force inlife has been able for many years to keep somekind of sanity. But it may now be on the decline.

REALITY THROUGH INSANITY——A Survey of the Neurotic Heroes in American Novels of thc 1960s

As if neurosis has become an epidemic disease,so many of the protagonists in American novelsof the 60s are mentally ill in one way or another:Herzog, with his wide-ranging disordered thoughts,is described psychologically as depressive andoccasionally paraniod. Yossarian, the absurdhero of Catch-22, is a manci depressive" withfear of conspired death as his main symptom.Oedina in The Crying of Lot 49 sincerely wishes shewere mentally ill after her long mysterious questafter an underground delivery system which mayeither be a real discovery or a paranoid fantasy.With numerous and murderous crimes on record,Howard Campell, a Nazi propagandist in MotherNight, is on the edge of madness and despair.