Extracranial transport of brain lymphatics via cranial nerve in human.

Extracranial waste transport from the brain interstitial fluid to the deep cervical lymph node (dCLN) is not extensively understood. The present study aims to show the cranial nerves that have a role in the transport of brain lymphatics vessels (LVs), their localization, diameter, and number using podoplanin (PDPN) and CD31 immunohistochemistry (IHC) and Western blotting. Cranial nerve samples from 6 human cases (3 cadavers, and 3 autopsies) were evaluated for IHC and 3 autopsies for Western blotting. The IHC staining showed LVs along the optic, olfactory, oculomotor, trigeminal, facial, glossopharyngeal, accessory, and vagus nerves. However, no LVs present along the trochlear, abducens, vestibulocochlear, and hypoglossal nerves. The LVs were predominantly localized at the endoneurium of the cranial nerve that has motor components, and LVs in the cranial nerves that had sensory components were present in all 3 layers. The number of LVs accompanying the olfactory, optic, and trigeminal nerves was classified as numerous; oculomotor, glossopharyngeal, vagus, and accessory was moderate; and facial nerves was few. The largest diameter of LVs was in the epineurium and the smallest one was in the endoneurium. The majority of Western blotting results correlated with the IHC. The present findings suggest that specific cranial nerves with variable quantities provide a pathway for the transport of wastes from the brain to dCLN. Thus, the knowledge of the transport of brain lymphatics along cranial nerves may help understand the pathophysiology of various neurological diseases.

Magnetic Resonance Imaging Findings in Patients With Duane Retraction Syndrome.

BACKGROUND: Duane retraction syndrome (DRS) is known to relate to the absence of the abducens nucleus, with abnormal innervation of the lateral rectus (LR) muscle by branchesof the oculomotor nerve (CN III). The purposes of this study were to investigate the morphological characteristics of the oculomotor nerve (CN III), the abducens nerve (CN VI), and the extraocular muscles in patients with clinically diagnosed Duane retraction syndrome (DRS) using MRI. In addition, we assessed the association between ocular motility, horizontal rectus muscle volumes, and CN III/VI in patients with Duane retraction syndrome (DRS). METHODS: The study comprised 20 orthotropic control subjects (40 eyes) and 42 patients with Duane syndrome (48 eyes), including 20 patients with DRS Type I (24 eyes), 5 patients with DRS Type II (6 eyes), and 17 patients with DRS Type III (18 eyes). Three-dimensional (3D) T1/2 images of the brainstem and orbit were obtained to visualize the cranial nerves, especially the abducens (VI) and oculomotor (III) nerves, as well as extraocular muscles. RESULTS: Based on the clinical classification, among 42 patients, MRI showed that the abducens nerves (CN VI) on the affected side were absent in 24 of 24 eyes (100%; 20 patients) with Type I DRS and in 16 of 18 eyes (88%; 16 patients) with Type III DRS. However, CN VI was observed in 6 of 6 eyes (100%; 5 patients) with Type II DRS and in 2 of 18 eyes (11%) with Type III DRS. CN III was observed in all patients. The oculomotor nerves on the affected side were thicker than those on the nonaffected contralateral side in DRS Type I ( P < 0.05) and Type III ( P < 0.05), but not in DRS Type II. Smaller LR and larger MR volumes were shown in the affected eye than that in the nonaffected eye in DRS Types I and III. Based on the presence or absence of CN VI, there was a tendency for thicker oculomotor nerves in the affected eye than in the nonaffected eye in the absence groups ( P < 0.05). However, no significant difference was found in the present group. In the CN VI absence groups, similar results were found in the affected eyes than in the nonaffected eyes as in DRS Types I and III. In addition, the presence of CN VI was correlated with better abduction ( P = 0.008). The LR and MR volumes have positive correlations with the oculomotor nerve diameter in the affected eye. However, there was no correlation between the range of adduction/abduction and the LR/MR ratio in patients with or without an abducens nerve. CONCLUSIONS: Different types of DRS have different characteristic appearances of CN VI and CN III on MRI. Horizontal rectus muscles have morphological changes to adapt to dysinnervation of CN VI and aberrant innervation of CN III. Thus, these neuroimaging findings may provide a new diagnostic criterion for the classification of DRS, improving the comprehension of the physiopathogenics of this disease.

Predictors of Surgical Outcomes in Patients with Abducens Nerve Schwannoma: A Comprehensive Systematic Review and a Case Report.

BACKGROUND: Abducens nerve (AN) schwannomas are extremely rare tumors. Clinical characteristics and factors that influence postoperative outcomes are not well defined. OBJECTIVE: To characterize clinical features of AN schwannomas and predictors of surgical outcomes. METHODS: PRISMA-guided systematic review of the literature on AN schwannomas was performed. Subsequently, univariate and multivariate regression analyses were performed to identify the predictive value of variables that influence postoperative outcomes. RESULTS: A total of 42 studies with 55 patients were evaluated. The mean age at presentation was 43.9 ± 14.6 years. The most common presenting symptom was cranial nerve VI palsy (69.1%). Cavernous sinus (49.1%) and prepontine cistern (36.3%) were the most commonly involved locations. Complete recovery after surgery was seen in 36.3% at a median follow-up of 28.4 ± 25.8 months. Preoperative AN palsy (P < 0.001), suboccipital approach (P = 0.007), and subtotal resection of tumor (P = 0.044) were significant protective factors for postoperative complications. Prepontine location and postoperative complications were poor prognostic indicators of AN recovery (odds ratio [OR], 0.10, P = 0.030 and OR, 0.10, P = 0.028, respectively). Subtotal resection was significantly correlated with higher odds of AN recovery (OR, 6.06; P = 0.040). CONCLUSIONS: AN schwannomas are rare but serious tumors that can cause significant morbidity, with only approximately one third of patients showing complete recovery after surgery. The suboccipital approach was a protective factor for postoperative complications, especially when combined with subtotal resection. Knowledge of these factors along with tumor characteristics helps optimize surgical planning and preoperative counseling.

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.

Vertebrobasilar dolichoectasia and other arterial abnormalities leading to abducens nerve palsy.

INTRODUCTION: Dolichoectatic vessels can cause cranial nerve dysfunction by either direct compression or ischemia. Abducens nerve palsy due to neurovascular compression by elongated, enlarged, tortuous or dilated arteries is an uncommon but important cause. AIM: To highlight neurovascular compression as a cause of abducens nerve palsy and discuss various diagnostic techniques. METHODS: Manuscripts were identified using the National Institutes of Health PubMed literature search system. Search terms included abducens nerve palsy, neurovascular compression, dolichoectasia and arterial compression. Inclusion criteria required that the articles were written in English. RESULTS: The literature search identified 21 case reports where abducens nerve palsy was due to vascular compression. Out of these 18 patients were male and the mean age was 54 years. Eight patients had unilateral right abducens nerve involvement; eleven patients had unilateral left nerve involvement and two patients had bilateral involvement. The arteries causing the compression were basilar, vertebral and anterior inferior cerebellar arteries. A compressed abducens nerve is not usually clearly detected on CT (Computed Tomography) or MRI (Magnetic Resonance Imaging). MRA (Magnetic Resonance Angiography), Heavy T2- WI (weighted imaging), CISS (constructive interference in steady state) and FIESTA (Fast Imaging Employing Steady-state Acquisition) are essential to demonstrate vascular compression of the abducens nerve. The various treatment options included controlling hypertension, glasses with prisms, muscle resection and microvascular decompression.

Isolated Sixth Nerve Palsies in a Child With Familial Hemophagocytic Lymphohistiocytosis Type 2.

ABSTRACT: A previously healthy 2-year-old boy presented with a left sixth cranial nerve palsy. There was a family history of multiple sclerosis and optic neuritis. Neuroimaging showed multiple foci of T2/FLAIR hyperintense signal abnormality in both cerebral hemispheres and in the brainstem. The initial diagnosis was suspicious for demyelinating disease. However, there was no clinical improvement after a course of corticosteroids, and there was no change in his follow-up MRI. He later developed bilateral sixth nerve palsies, with esotropia addressed with bilateral medial rectus botulinum toxin injections. A brain biopsy was planned. However, his 3-month-old sister was separately admitted for fever and pancytopenia. She had markedly elevated ferritin, D-dimer, triglycerides, sIL-2R, CXCL9, and IL-18 and low fibrinogen. Her bone marrow biopsy showed hemophagocytosis. Genetic testing of both siblings revealed biallelic mutations in the PRF1 locus. The final diagnosis of familial hemophagocytic lymphohistiocytosis Type 2 was made. Both siblings underwent chemotherapy. The boy's sixth nerve palsies and MRI abnormalities resolved. Both siblings then went on to undergo bone marrow transplant.

An atypical anatomical variation of the petrosphenoidal ligament in a newborn cadaver.

PURPOSE: To report an atypical anatomical variation of the petrosphenoidal ligament in a newborn cadaver and to discuss its clinical significance. METHODS: During a study of ten newborn cadavers, the skull base was dissected to reveal the anatomy of the petrosphenoidal ligament and its relationship with the abducens nerve. An atypical anatomical variation was observed, and this is described. The length of the right and left ligaments to the point where it splits into two arms, the joint length of the two ligaments at the junction of the clivus, the length of the ligament proceeding to the posterior clinoid process, and the abducens nerve's diameter as it passes below the ligament were measured on ImageJ software. RESULTS: The petrosphenoidal ligaments were y-shaped, and the attachment of the proximal ligaments was bifid. In the midline above the clivus, some ligament bundles joined the contralateral petrosphenoidal ligament, whilst another group of bundles originated at the posterior clinoid process. At the entry to Dorello's canal, the abducens nerve had a diameter of 0.59 mm on the left and 0.65 mm on the right. The part of the ligaments converging on the clivus in the midline after dividing into two arms was 10.68 mm. CONCLUSIONS: We think that this case report will provide useful information for surgical procedures to the petroclival region, transnasal surgical approaches, and surgical interventions involving the carotid artery.

Microanatomy of the central myelin portion and transitional zone of the oculomotor and abducens nerves.

BACKGROUND: The microanatomy of the central myelin portion and transitional zone of several cranial nerves including trigeminal, facial, vestibulocochlear, glossopharyngeal, and vagus nerves have been clearly demonstrated to provide information for neurovascular compression syndrome such as trigeminal neuralgia and hemifacial spasm. However, the study of oculomotor and abducens nerve is limited. MATERIALS AND METHODS: Oculomotor and abducens nerves were harvested with a portion of brainstem and embedded in paraffin. Longitudinal and serial sections from ten of each cranial nerve were stained and a photomicrograph was taken to make the following observations and measurements: 1) patterns of central myelin portion, 2) length of central myelin portion, and 3) depth of central myelin- peripheral myelin transitional zone. RESULTS: For oculomotor nerve, the longest central myelin bundle was always seen on the first nerve bundle and that the length of central myelin decreased gradually. For abducens nerve, morphological patterns were classified into four types based on number of nerve rootlets emerging from the brainstem and number of nerve bundles in each rootlet. Length of central myelin portion was between 0.36-6.10 mm (2.75 ± 0.83 mm) and 0.13-5.01 mm (1.66 ± 1.39 mm) for oculomotor and abducens nerves, respectively. The oculomotor nerve transitional zone depth was 0.07-058 mm (0.23 ± 0.07 mm), while for abducens nerve, depth was 0.05-0.40 mm (0.16 ± 0.07 mm). Positive weak correlations between central myelin and depth of TZ were found in oculomotor nerve (r +0.310, p < 0.05) and abducens nerves (r +0.413, p < 0.05). CONCLUSIONS: Detailed microanatomy of the central myelin and transitional zone might be beneficial for locating the site of compression in neurovascular conflicts at oculomotor and abducens nerves.

Concomitant completely ossified trigeminal pore and Dorello's canal.

Commonly, the trigeminal and abducens nerve course to the middle cranial fossa, beneath the tentorial border (posterior petroclinoid dural ligament) and, respectively, beneath Grüber's petrosphenoidal ligament, in Dorello's canal. It is hereby reported a rare unilateral association of anatomic variants which was found when the brain computed tomography angiography of a 56-year-old male patient was observed. On the left side, the tentorial border was ossified above the petrous apex, resulting in a tentorial bar 1.96 cm long that transformed the trigeminal pore into a completely ossified one. On that side was also found an ossified petrosphenoidal ligament determining a completely ossified Dorello's canal. On the opposite side a 2.9 mm long clinoid bar extended from the posterior clinoid process to the anterior one. Although these bars are not common in humans they should be documented in computed tomography in cases with associated trigeminal neuralgia and abducens nerve palsy.

MRI Diagnosis of Clival Cancer and Sixth Nerve Palsy.

BACKGROUND: Imaging diagnosis of clival cancer may be difficult, in part because of normal variation in marrow signal with aging. Identifying whether clival cancer has damaged the sixth cranial nerve is a further challenge because minimal clival abnormalities could impinge on the nerve, which travels very close to the clivus. METHODS: Two neuroradiologists, who were unaware of previous imaging and clinical diagnoses, reviewed MRI studies of 25 patients with cancer but no clival involvement and no sixth nerve palsy, 24 patients with clival cancer but without sixth nerve palsy, and 31 patients with clival cancer and sixth nerve palsy. The radiologists were tasked with determining whether there was clival cancer, whether there was a sixth nerve palsy and its laterality, and with indicating the pulse sequences used to make those determinations. RESULTS: Both neuroradiologists correctly identified all 25 cases with a normal clivus. In about half of those cases, they depended on finding a homogeneously bright marrow signal; in the remaining cases, they excluded cancer by determining that the clivus was not expanded and that there were no focal signal abnormalities. Both neuroradiologists correctly identified clival cancer in 54 (98%) of the 55 cases with and without sixth nerve palsy. In doing so, they relied mostly on clival expansion but also on focal signal abnormalities. Both neuroradiologists were at least 80% correct in identifying a sixth nerve palsy, but they often incorrectly identified a palsy in patients who did not have one. When there was a one-sided signal abnormality or the clivus was expanded in one direction, both neuroradiologists were accurate in identifying the side of the sixth nerve palsy. CONCLUSION: Current MRI pulse sequences allow accurate differentiation of a normal from a cancerous clivus. When the marrow signal is not homogeneously bright in adults, cancer can be diagnosed on the basis of clival expansion or focal signal abnormalities. MRI is less accurate in predicting the presence of a sixth nerve palsy. However, the side of a unilateral palsy can be predicted when the clivus is clearly expanded in one direction or there is a focal signal abnormality on one side.

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.

Reduced activity of vertically acting motoneurons during convergence.

Previous studies have revealed unexpected relationships between the firing rates of horizontally acting motoneurons and vergence. During a vergence task, for example, antidromically identified abducens internuclear neurons show a negative correlation between vergence angle and firing rate, which is the opposite of the modulation displayed by the medial rectus motoneurons to which they project. For a given horizontal eye position, medial rectus motoneurons discharge at a higher rate if the eyes are converged than if the same eye position is reached during a task that requires version; paradoxically, however, the horizontal rectus eye muscles show corelaxation during vergence. These complex and unexpected relationships inspired the present author to investigate whether the tonic firing rates of vertically acting motoneurons in oculomotor nucleus are correlated with vergence angle. Monkeys were trained to fixate a single, randomly selected, visual target among an array of 60 red plus-shaped LEDs, arranged at 12 different distances in three-dimensional space. The targets were arranged to permit dissociation of vertical eye position and vergence angle. Here I report, for the first time, that most vertically acting motoneurons in oculomotor nucleus show a significant negative correlation between tonic firing rate and vergence angle. This suggests the possibility that there may be a general corelaxation of extraocular muscles during vergence.NEW & NOTEWORTHY An array of 60 plus-shaped LEDs, positioned at various locations in three-dimensional space, was used to elicit conjugate and disjunctive saccades while single neurons in oculomotor nucleus were recorded from rhesus monkeys. This study demonstrates that most vertically acting motoneurons in oculomotor nucleus discharge at a lower rate when the eyes are converged.