BDNF Influence on Adult Terminal Axon Sprouting after Partial Deafferentation.

BDNF is a neurotrophin family member implicated in many different neuronal functions, from neuronal survival during development to synaptic plasticity associated with processes of learning and memory. Its presence in the oculomotor system has previously been demonstrated, as it regulates afferent composition of extraocular motoneurons and their firing pattern. Moreover, BDNF expression increases after extraocular motoneuron partial deafferentation, in parallel with terminal axon sprouting from the remaining axons. To elucidate whether BDNF could play an active role in this process, we performed partial deafferentation of the medial rectus motoneurons through transection of one of the two main afferents, that is, the ascending tract of Deiters, and injected BDNF into the motoneuron target muscle, the medial rectus. Furthermore, to check whether BDNF could stimulate axon sprouting without lesions, we performed the same experiment without any lesions. Axon terminal sprouting was assessed by calretinin immunostaining, which specifically labels the remaining afferent system on medial rectus motoneurons, the abducens internuclear neurons. The results presented herein show that exogenous BDNF stimulated terminal axon growth, allowing the total recovery of synaptic coverage around the motoneuron somata. Moreover, calretinin staining in the neuropil exceeded that present in the control situation. Thus, BDNF could also stimulate axonal sprouting in the neuropil of intact animals. These results point to an active role of BDNF in plastic adaptations that take place after partial deafferentation.

Magnetic resonance imaging features of COVID-19-related cranial nerve lesions.

The complete features of the neurological complications of coronavirus disease 2019 (COVID-19) still need to be elucidated, including associated cranial nerve involvement. In the present study we describe cranial nerve lesions seen in magnetic resonance imaging (MRI) of six cases of confirmed COVID-19, involving the olfactory bulb, optic nerve, abducens nerve, and facial nerve. Cranial nerve involvement was associated with COVID-19, but whether by direct viral invasion or autoimmunity needs to be clarified. The development of neurological symptoms after initial respiratory symptoms and the absence of the virus in the cerebrospinal fluid (CSF) suggest the possibility of autoimmunity.

A clinical study of ocular motor nerve functions after petroclival meningioma resection.

BACKGROUND: Ocular motor dysfunction is one of the most common postoperative complications of petroclival meningioma. However, its incidence, recovery rate, and independent risk factors remain poorly explored. METHODS: A prospective analysis of 31 petroclival meningiomas was performed. Operative approaches were selected by utilizing a new 6-region classification of petroclival meningiomas we proposed. Two scores were used to evaluate the functions of the oculomotor and abducens nerves. Pearson correlation analysis and binary logistic regression analysis were used to identify independent risk factors for intraoperative oculomotor and abducens nerve injury. RESULTS: Postoperative new-onset dysfunctions in the pupillary light reflex and eye/eyelid movements as well as abducens paralysis were detected in eight (25.8%), ten (32.3%) and twelve (38.7%) cases, respectively. Their corresponding recovery rates after 6 months of follow-up were 75% (6/8), 80% (8/10), and 83.3% (10/12), respectively, and their mean times to start recovery were 4.03, 2.43, and 2.5 months, respectively. Tumor invasion into the suprasellar region/sphenoid sinus was the only risk factor for dysfunctions in both the pupillary light reflex (p = 0.001) and eye/eyelid movements (p = 0.002). Intraoperative utilization of the infratrigeminal interspace was the only risk factor for dysfunction in eyeball abduction movement (p = 0.004). CONCLUSIONS: Dysfunctions of the oculomotor and abducens nerves recovered within 6 months postoperatively. Tumor extension into the suprasellar region/sphenoid sinus was the only risk factor for oculomotor nerve paralysis. Eye/eyelid movements were more sensitive than the pupillary light reflex in reflecting nerve dysfunctions. Intraoperative utilization of the infratrigeminal interspace was the only risk factor for abducens nerve paralysis.

Radiosurgery in trochlear and abducens nerve schwannomas: case series and systematic review.

INTRODUCTION: Schwannomas involving the occulomotor cranial nerves  (CNs; III, IV and VI), can be disabling, due to the associated diplopia and decreased quality of life and are extremely rare. We evaluated the role of Gamma Knife surgery (GKS) in these cases. METHODS: Five patients with CN IV and VI schwannomas (three and two, respectively) were treated in Lausanne University Hospital between 2010 and 2015. Four benefitted from upfront GKS and one from a combined approach (planned subtotal resection followed by GKS), due to a large preoperative tumour volume (size, 3 × 2 × 2.5 cm; volume, 7.9 ml), with symptomatic mass effect and oedema, as well as an entrapement cyst at the brainstem interface, in a young patient. Neuro-ophtalmological evaluation was performed at baseline and during each follow-up time-point. A systematic literature review is presented and compared to the present report. RESULTS: The mean follow-up was 44.4 months (12-54). Initial clinical presentation was diplopia in four cases and cavernous sinus syndrome in one. The marginal dose was 12 Gy in all cases. The mean target volume was 1.51 cm3 (0.086-5.8). The mean prescription isodose volume (PIV) was 1.71 cm3 (0.131-6.7). At last follow-up, all patients presented with disappearance of the baseline symptoms. Tumour control was achieved in 100%, with decrease in volume in all cases. The systematic review analysed 11 peer-reviewed studies, with a total of 35 patients. For uniformly reported CN VI, the mean marginal radiation dose ranged between 12 and 12.5 Gy, with disappearance of symptoms in 12.5%, improvement in 31.25%, stabilisation in 6.25%, worsening in 12.5%. Tumour volume decreased in all cases. CONCLUSIONS: Our data suggest that first intention GKS is a safe and effective option for patients with small to medium size oculomotor schwannomas, providing a high rate of clinical alleviation and tumour control. When the initial tumour volume is too large for first intention GKS, a combined approach with planned subtotal resection followed by GKS can be performed, with favourable and comparable outcomes as in upfront GKS.

Acute Abducens Nerve Paralysis in the Pediatric Emergency Department: Analysis of 14 Patients.

OBJECTIVES: Sixth cranial nerve (SCN) palsy is an uncommon but important neurological problem in patients admitted to pediatric emergency department. The underlying etiology of SCN palsy has a wide range from viral infections to intracranial tumors; therefore, a careful and systematic approach is necessary while examining these patients. METHODS: Fourteen patients who presented with acute SCN paralysis to pediatric emergency department during the last 10 years were examined. RESULTS: The age at the time of admission ranged between 14 months and 16 years (median, 9.5 years). Of the 14 patients, 5 were girls and 9 were boys. A total of 3 of the 14 patients had bilateral cranial nerve VI paralysis, and 9 patients had additional abnormal findings on neurological examination. Neuroimaging studies included cranial tomography (n = 3) and brain magnetic resonance imaging in all patients. The underlying etiology was malignancy (n = 3); glioma, medulloblastoma, acute lymphoblastic leukemia, and dural sinus thrombosis (n = 2); as well as Guillain-Barre syndrome (n = 2), multiple sclerosis (n = 1), pseudotumor cerebri (n = 1), and meningitis (n = 1). The remaining 4 patients had miscellaneous benign etiologies. CONCLUSIONS: Other lesions of primary brain tumors causing increased intracranial pressure constitute 50% of the underlying etiology, followed by Guillain-Barre syndrome (14.2%). However, these patients had neurological symptoms signs, in addition to diplopia or SCN paralysis. Patients admitted to pediatric emergency department with acute SCN paralysis should be examined in detail to disclose the underlying etiology especially if they present with additional clinical signs or symptoms.

MRI findings in Duane's ocular retraction syndrome.

AIM: To investigate the innervation pattern of extra-ocular muscles in patients with clinically diagnosed Duane's ocular retraction syndrome (DRS) using magnetic resonance imaging (MRI). MATERIALS AND METHODS: The study population consisted of 11 patients. Six patients had type I DRS (eight eyes), four patients had type II DRS (five eyes) and one patient had inverse DRS. Images were acquired using a Siemens 3 T MRI system. The type of DRS, corresponding innervation findings, and condition of the affected muscles were evaluated by two experienced neuroradiologists in consensus. RESULTS: All patients with clinically diagnosed DRS type I showed absence of the abducens nerve (CN6), hypoplasia of the superior oblique muscle (SOM), and aberrant innervation of lateral rectus muscle (LRM) by an extra branch of oculomotor nerve (CN3). All patients with type II DRS show dual-innervation of the LRM (by CN6 and an aberrant CN3 branch) and hypoplasia of SOM. The single patient with inverse DRS showed hypoplasia of CN3, the medial rectus muscle (MRM), the inferior rectus muscle (IRM), and the inferior oblique muscle (IOM). CONCLUSION: Each type of DRS has characteristic MRI appearances. Therefore, MRI is a useful diagnostic tool for the confirmation and classification of suspected cases of DRS.

Ossification of the petrosphenoidal ligament: unusual variation with the potential for abducens nerve entrapment in Dorello's canal at the skull base.

Variable bony anatomy at the skull base may result in compression or entrapment of exiting cranial nerves. The authors present an unusual variation of bilateral ossification of the roof of Dorello's canal and review the germane literature. Clinicians might consider ossification of the petrosphenoidal ligament (also called Gruber's ligament) in patients with unexplained cases of abducens nerve palsy.

Abducens nerve is present in patients with type 2 Duane's retraction syndrome.

OBJECTIVE: To determine whether the abducens nerve is present in patients with type 2 Duane's retraction syndrome (DRS). DESIGN: Retrospective, observational case series. PARTICIPANTS: Twelve consecutive patients diagnosed with type 2 DRS. METHODS: A retrospective review of medical records of ophthalmologic examination and thin-sectioned magnetic resonance imaging (MRI) at the brainstem level and the orbit was performed on 12 patients who showed the typical signs of type 2 DRS, including adduction deficit; globe retraction; narrowing of fissure on adduction; and upshoot, downshoot, or both. MAIN OUTCOME MEASURES: Presence of the abducens nerve and any other extraocular muscle abnormalities discovered by MRI scan. RESULTS: Magnetic resonance imaging revealed the presence of the abducens nerve in all the affected eyes (n = 13) of 12 patients with type 2 DRS. CONCLUSIONS: The abducens nerve is present on the affected side in type 2 Duane's retraction syndrome.

The fate of the oculomotor system in clinical bilateral anophthalmia.

The interdependence of the development of the eye and oculomotor system during embryogenesis is currently unclear. The occurrence of clinical anophthalmia, where the globe fails to develop, permits us to study the effects this has on the development of the complex neuromuscular system controlling eye movements. In this study, we use very high-resolution T2-weighted imaging in five anophthalmic subjects to visualize the extraocular muscles and the cranial nerves that innervate them. The subjects differed in the presence or absence of the optic nerve, the abducens nerve, and the extraocular muscles, reflecting differences in the underlying disruption to the eye's morphogenetic pathway. The oculomotor nerve was present in all anophthalmic subjects and only slightly reduced in size compared to measurements in sighted controls. As might be expected, the presence of rudimentary eye-like structures in the socket appeared to correlate with development and persistence of the extraocular muscles in some cases. Our study supports in part the concept of an initial independence of muscle development, with its maintenance subject to the presence of these eye-like structures.

Clinically unsuspected neuritic leprosy with caseation necrosis.

Leprosy is a devastating disease caused by Mycobacterium leprae. It includes a spectrum of clinicopathological lesions. Neuritic leprosy with caseation necrosis (abscess) manifesting as a soft tissue mass is a relatively rare presentation of leprosy. Here, the authors report their experience with three patients with neuritic leprosy. The patients presented with swellings in the right ulnar nerve, the right great auricular nerve, and the temporal branch of the right sixth cranial nerve. The clinical impression was that of tumorous masses. Gross examination of the biopsy specimens revealed caseous necrotic materials. Further histological evaluation disclosed tuberculoid granulomas with extensive caseation necrosis. Stains for acid-fast bacilli were positive in the third case. A comparison between the caseation encountered in the tuberculoid neurotic leprosy and the neurolysis of lepromatous neurotic leprosy has been also discussed. The findings here emphasize "mass lesion with necrosis" as a possible clinical presentation of the neuritic leprosies. The clinicopathologic features were addressed and the relevant literature was reviewed.

The Abducens Nerve: Anatomy and Pathology.

The abducens, or the sixth cranial nerve, is purely motor and runs a long course from the brainstem to the lateral rectus. Travels with the inferior petrosal sinus through the Dorello's canal before entering the cavernous sinus. Based on the location of an abnormality, other neurologic structures may be involved with the disturbs related to this nerve. This article aims to review the abducens nerve anatomy and demonstrates the imaging aspect of the diseases that most commonly affect it.

Review of the Petroclinoid Ligament.

An ossified left petroclinoid ligament was found during routine dissection of the skull base in an adult male cadaver. The petroclinoid ligament is clinically and surgically important given its anatomical relationships to cranial nerves III, V, and VI, so its ossification is a risk factor for injuries due to trauma, increased intracranial pressure, and vascular and tumor compression resulting in abducens and oculomotor palsies. The causes of petroclinoid ligament ossification are yet to be completely elucidated although several reports have associated them with age-related and physiological processes. Assessing the integrity of the petroclinoid ligament is important during skull base surgical interventions to avoid postoperative complications. Therefore, this paper reviews the petroclinoid ligament and its variation, the ossified petroclinoid ligament.

Abducens Nerve Schwannoma: First Case to Be Treated With an Expanded Endonasal Approach.

Abducens nerve schwannomas are incredibly rare, with very few cases being reported previously. Our patient is the first to have been treated through use of an endoscopic endonasal approach. A 61-year-old woman presented with diplopia over a 1-year period. Magnetic resonance imaging identified a 2.8-cm lesion expanding into her right sphenoid sinus. She underwent an endoscopic endonasal approach for histological diagnosis and clearance of the lesion. Intraoperative exploration found the lesion to be originating from Dorello canal. Histological analysis confirmed a benign schwannoma. Following a multidisciplinary case review, we have followed a conservative approach and she remains well on radiological surveillance. In patients presenting with a sixth nerve palsy/paresis and a concomitant sphenoid lesion, clinicians should consider an abducens schwannoma as a possible diagnosis.

Cavernous Sinus Swelling and Abducens Nerve Paresis Due to Intracranial Hypotension.

The most common neurological symptom of spontaneous intracranial hypotension (SIH) is abducens nerve paresis, and the precise pathophysiology is unclear. The accepted explanation is traction on the cranial nerves caused by the downward displacement of the cranial content. We herein report magnetic resonance imaging of SIH that can explain the mechanism underlying abducens nerve paresis. The cavernous sinuses were particularly thickened compared with the surrounding dura. This phenomenon can be explained by venous swelling, which can occur after leakage of cerebrospinal fluid in a closed cavity. This swelling pushes the abducens nerve up, which then causes abducens nerve paresis.

Rathke's cleft cyst presenting as bilateral abducens nerve palsy.

We present a patient with a Rathke's cleft cyst who presented with rapidly progressive bilateral 6th nerve palsy. A 20-year-old woman with a history of cleft palate, hypertension, and hydronephrotic kidneys presented with a one month history of headache, associated with dizziness and diplopia on horizontal gaze. Examination was significant for profound bilateral 6th nerve palsies. Magnetic resonance imaging showed a hypodense mass that filled the sella and compressed the right cavernous sinus without contacting the optic chiasm. Pituitary function was normal. An endoscopic, transnasal transsphenoidal resection of the lesion was performed; microscopic examination revealed a Rathke's cleft cyst. Surgical excision resulted in near complete resolution of the bilateral 6th nerve palsy. Rathke's cleft cysts are an unusual cause of bilateral sixth nerve palsy and represent a potential cause of cranial neuropathy.

Can Ophthalmologic Examination Predict Abducens Nerve Recovery After Endoscopic Skull Base Surgery?

OBJECTIVES: While abducens nerve palsy (ANP) is a known risk in the setting of some endoscopic endonasal skull base surgery (ESBS), frequency and prognosis of post-operative palsy remain unknown. Our goals were to determine the frequency and prognosis of ANP after high-risk ESBS, and identify factors associated with recovery. METHODS: Retrospective case series of all patients with pathology at highest risk for abducens nerve injury (pituitary adenoma, chordoma, meningioma, chondrosarcoma, cholesterol granuloma) generated a list of patients with abducens nerve palsy after ESBS performed from 2011-2016. A validated ophthalmologic clinical grading scale measuring lateral rectus duction from 0 to -5 (full motion to inability to reach midline) was measured at multiple time points to assess recovery of ANP. RESULTS: Of 655 patients who underwent ESBS with increased risk of abducens injury, 40 (6.1%) post-operative palsies were identified and 39 patients with dedicated examination at multiple time points were included in subsequent analysis. Complete resolution was noted in 25 patients (64%) within 12 months. While 19 of 23 (83%) with a partial palsy had complete resolution, only six of 16 (38%) with a complete palsy resolved entirely (P = .005; Fisher's exact test). All six patients with delayed onset of palsy resolved (P = .070; Fisher's exact test). Meningioma and chordoma had higher rates of both temporary and permanent post-operative ANP (P < .0001; Fisher's exact). CONCLUSIONS: The frequency of post-operative ANP following ESBS is low, even in high-risk tumors. While only a minority of complete abducens nerve palsies recover, patients with partial or delayed palsy post-operatively are likely to recover function without intervention. LEVEL OF EVIDENCE: IV Laryngoscope, 131:513-517, 2021.