Transmembrane protein 53 craniotubular dysplasia (OMIM # 619727): The skeletal disease and consequent blindness of this new disorder.

Craniotubular dysplasia, Ikegawa type (OMIM #619727) denotes the autosomal recessive skeletal disease identified in 2021 featuring blindness acquired in childhood. Five young members of four Indian families harbored a homozygous indel within TMEM53 (OMIM *619722), the gene that encodes transmembrane protein 53 (TMEM53). When intact, TMEM53 spans the nuclear envelope of osteoprogenitor cells, dampens BMP-SMAD signaling, and thereby slows bone formation. Consequently, defective TMEM53 accelerates osteogenesis. Herein, an American boy is compound heterozygous for a novel deletion and a novel missense mutation within TMEM53. His vision and sensorineural hearing became impaired. Radiographic survey revealed diploic thickening of his skull, broad calvarial and facial bones, skeletal modeling errors, vertebral body flattening, wide ribs, and osteopenia of expanded bones. DXA areal bone density (gm/cm2) Z-scores were low. His optic, auditory, and spinal canals were narrow. Mineral metabolism was intact. Serum alkaline phosphatase and osteocalcin levels were normal yet CTX was high. Iliac crest histomorphometry documented accelerated bone formation. His acute vision loss briefly improved following prednisone administration, optic canal decompression, and optic nerve sheath fenestration, but then progressed despite further surgeries and zoledronate treatment aimed to suppress bone turnover. Next generation sequencing of genes associated with elevated skeletal mass, including from high bone turnover, did not suggest an etiology. Whole genome sequencing then revealed within TMEM53: i) a paternally transmitted 54-base deletion, which included the mRNA splice acceptor site for exon 2 as well as 31 bases of exonic sequence (c. 62-23_92del), and ii) a maternally transmitted missense variant (c.650C > T, p.Ser217Leu: NM_024587.4/NP_078863.2) which is extremely rare in gnomAD (frequency = 0.000036), replaces Ser217 highly conserved across species, and is scored as damaging by SIFT and Mutation Taster. We call this new osteopathy TMEM53 craniotubular dysplasia.

Endoscopy-Assisted Microneurosurgery for Sella and Optic Foramen Invading Anterior Cranial Fossa Base Meningiomas.

BACKGROUND: Anterior skull base meningioma produces symptoms as a result of mass effect and neurovascular compression. The bony anatomy of the anterior skull base is complex and houses the critical cranial nerves and vessels. Traditional microscopic approaches remove these tumors effectively but require extensive brain retraction and bone drilling. Endoscope assistance offers the advantages of a smaller incision, less brain retraction, and bone drilling. The most significant advantage of endoscope-assisted microneurosurgery for lesions invading the sella and optic foramen is the complete resection of the sellar and foraminal components frequently responsible for recurrence. OBJECTIVE: In this report, we describe the technique of endoscope-assisted microneurosurgical resection of anterior skull base meningiomas invading the sella and foramen. METHODS: We present 10 cases and 3 case examples of endoscope-assisted microneurosurgery for meningiomas invading the sella and optic foramen. This report presents the operating room setup and surgical details to resect sellar and foraminal tumors. The surgical procedure is presented as a video. RESULTS: Endoscope-assisted microneurosurgery yielded excellent clinical and radiologic results and no recurrence at the last follow-up of meningiomas invading the sella and optic foramen. The present article discusses the challenges faced with endoscope-assisted microneurosurgery, techniques, and challenges in the procedure. CONCLUSIONS: Endoscope assistance enables complete tumor excision under vision with less retraction and bone drilling in anterior cranial fossa meningioma, invading the chiasmatic sulcus, optic foramen, and sella. The mixed use of microscope and endoscope makes it safer and saves time and is like bringing out the best of both worlds.

Direct targeting of the mouse optic nerve for therapeutic delivery.

BACKGROUND: Animal models of optic nerve injury are often used to study central nervous system (CNS) degeneration and regeneration, and targeting the optic nerve is a powerful approach for axon-protective or remyelination therapy. However, the experimental delivery of drugs or cells to the optic nerve is rarely performed because injections into this structure are difficult in small animals, especially in mice. NEW METHOD: We investigated and developed methods to deliver drugs or cells to the mouse optic nerve through 3 different routes: a) intraorbital, b) through the optic foramen and c) transcranial. RESULTS: The methods targeted different parts of the mouse optic nerve: intraorbital proximal (intraorbital), intracranial middle (optic-foramen) or intracranial distal (transcranial) portion. COMPARISON WITH EXISTING METHODS: Most existing methods target the optic nerve indirectly. For instance, intravitreally delivered cells often cannot cross the inner limiting membrane to reach retinal neurons and optic nerve axons. Systemic delivery, eye drops and intraventricular injections do not always successfully target the optic nerve. Intraorbital and transcranial injections into the optic nerve or chiasm have been performed but these methods have not been well described. We approached the optic nerve with more selective and precise targeting than existing methods. CONCLUSIONS: We successfully targeted the murine optic nerve intraorbitally, through the optic foramen, and transcranially. Of all methods, the injection through the optic foramen is likely the most innovative and fastest. These methods offer additional approaches for therapeutic intervention to be used by those studying white matter damage and axonal regeneration in the CNS.

Endoscope-Assisted Microsurgical Removal of an Optic Foramen Meningioma through a Frontolateral Minicraniotomy.

A 72-year-old male patient with visual disturbance of the right eye was diagnosed with a small meningioma of the right optic foramen extending to the carotid cistern. The operation was performed through an individually tailored frontolateral minicraniotomy via a curvilinear skin incision behind the hairline. Endoscope-assisted microsurgical technique was used to resect the lesion. The roof of the optic canal was partly removed to get access to the intraforaminal tumor parts. The lesion could be completely removed and the patient showed a satisfactory visual recovery in the follow-up examinations. The link to the video can be found at: https://youtu.be/p8EZx7aryeQ .

Carotico-clinoid foramina and a double optic canal: A case report with neurosurgical implications.

BACKGROUND: The lesser wing of the sphenoid is a clinically important structure, particularly with regard to its anatomical relationship with neurovascular structures including the optic nerve, ophthalmic artery, and internal carotid artery. Anterior clinoidectomy, a neurosurgical procedure utilized to access paraclinoid aneurysms and neoplasms, is often complicated by the presence of anatomical variants including the carotico-clinoid foramen and the accessory optic canal. CASE DESCRIPTION: A rare case report is presented documenting the simultaneous occurrence of bilateral carotico-clinoid foramina and a unilateral accessory optic canal. CONCLUSION: The presence of an accessory optic canal may be misconstrued as a carotico-clinoid foramen or pneumatization of the anterior clinoid process, lesser sphenoidal wing, or optic strut. The case report documents two clinically important variant structures occurring ipsilaterally, each with the potential to masquerade as the other radiographically and present complications to both neurosurgeons and radiologists. Knowledge of the unique combination of anatomical variants presented in this report may prevent adverse surgical events during anterior clinoidectomy procedures including hemorrhage of the ophthalmic artery or internal carotid artery and subsequent vision loss or death.

Tratamiento quirúrgico de los meningiomas del foramen óptico: técnica y resultados de una serie de 18 pacientes / Surgical treatment of optic foramen meningiomas: technique and results of a series of 18 patients

Introducción: los meningiomas del foramen óptico producen un rápido deterioro de la función visual aún cuando su tamaño es pequeño, por eso su diagnóstico y manejo difiere del resto de los meningiomas clinoideos. El propósito de este estudio es presentar la técnica y los resultados de nuestro manejo quirúrgico de meningiomas foraminales (MF). Pacientes y Métodos: se llevó a cabo una revisión de las historias clínicas de 47 pacientes con meningiomas primarios intraorbitarios. Se realizaron 52 cirugías en los pacientes con MF. Se empleó una craneotomía fronto-orbitaria, seguida de una descompresión extradural del canal óptico, resección del componente intraorbitario y exploración intradural del nervio óptico. Resultados: de los 12 pacientes con MF que presentaban la visión conservada, la agudeza visual fue preservada en 7 casos, mejoró en 2, y empeoró en 3. En 18 pacientes, el principal síntoma fue exoftalmos y en 35 pacientes ceguera unilateral. Ocurrieron 6 recurrencias, 2 a 10 años después de la resección quirúrgica. Cinco de ellos fueron reoperados. Se indicó radioterapia después de la recurrencia en 3 pacientes. Conclusión: el manejo de los MF continúa siendo controvertido y frecuentemente se propone un tratamiento conservador. Basados en nuestros hallazgos de frecuente extensión intracraneal, proponemos realizar una resección total o subtotal del tumor, preservando el nervio óptico en pacientes con visión prequirúrgica conservada.

Introduction: optic foramen meningiomas produce rapid deterioration of visual function even when its size is small, so its diagnosis and management differs from other clinoidal meningiomas. The purpose of this study is to present the technique and results of our surgical management of foraminal meningiomas (FM).Patients and Methods: a review of medical records of 47 patients harboring primary intraorbital meningiomas (PIM) was performed. In PIM patients fifty two operations were carried out. Fronto-orbital craniotomy was employed followed by extradural decompression of the optic canal, resection of the intraorbital component, and exploration of the optic nerve intradurally.Results: among 12 patients with PIM who had useful vision preoperatively the visual acuity was preserved in 7 cases, improved in 2, and worsened in 3 cases. In 18 patients exophthalmos was the main symptom and in 35 patients unilateral blindness. Six recurrences occurred 2 to 10 years after surgery. Five of them were reoperated on. We indicated radiotherapy after recurrence in 3 patients.Conclusion: the management of PIM remains controversial and conservative management is frequently proposed. Based on our frequent findings of intracranial extension, our approach has been to perform a total or subtotal removal of the tumor, sparing the optic nerve in patients with useful preoperative vision.