Graffeo, Christopher S.

Abstract Introduction Ki-67 is often used as a proliferation index to evaluate how aggressive a tumor is and its likelihood of recurrence. Vestibular schwannomas (VS) are a unique benign pathology that lends itself well to evaluation with Ki-67 as a potential marker for disease recurrence or progression following surgical resection. Methods All English language studies of VSs and Ki-67 indices were screened. Studies were considered eligible for inclusion if they reported series of VSs undergoing primary resection without prior irradiation, with outcomes including both recurrence/progression and Ki-67 for individual patients. For published studies reporting pooled Ki-67 index data without detailed by-patient values, we contacted the authors to request data sharing for the current meta-analysis. Studies reporting a relationship between Ki-67 index and clinical outcomes in VS for which detailed patients' outcomes or Ki-67 indices could not be obtained were incorporated into the descriptive analysis, but excluded from the formal (i.e., quantitative) meta-analysis. Results A systematic review identified 104 candidate citations of which 12 met inclusion criteria. Six of these studies had accessible patient-specific data. Individual patient data were collected from these studies for calculation of discrete study effect sizes, pooling via random-effects modeling with restricted maximum likelihood, and meta-analysis. The standardized mean difference in Ki-67 indices between those with and without recurrence was calculated as 0.79% (95% confidence interval [CI]: 0.28–1.30; p = 0.0026). Conclusion Ki-67 index may be higher in VSs that demonstrate recurrence/progression following surgical resection. This may represent a promising means of evaluating tumor recurrence and potential need for early adjuvant therapy for VSs.

Abstract Introduction Although endonasal endoscopic approaches (EEA) to the orbit have been previously reported, a didactic resource for educating neurosurgery and otolaryngology trainees regarding the pertinent anatomy, techniques, and decision-making pearls is lacking. Methods Six sides of three formalin-fixed, color latex–injected cadaveric specimens were dissected using 4-mm 0- and 30-degree rigid endoscopes, as well as standard endoscopic equipment, and a high-speed surgical drill. The anatomical dissection was documented in stepwise three-dimensional (3D) endoscopic images. Following dissection, representative case applications were reviewed. Results EEA to the orbit provides excellent access to the medial and inferior orbital regions. Key steps include positioning and preoperative considerations, middle turbinate medialization, uncinate process and ethmoid bulla removal, complete ethmoidectomy, sphenoidotomy, maxillary antrostomy, lamina papyracea resection, orbital apex and optic canal decompression, orbital floor resection, periorbita opening, dissection of the extraconal fat, and final exposure of the orbit contents via the medial-inferior recti corridor. Conclusion EEA to the orbit is challenging, in particular for trainees unfamiliar with nasal and paranasal sinus anatomy. Operatively oriented neuroanatomy dissections are crucial didactic resources in preparation for practical endonasal applications in the operating room (OR). This approach provides optimal exposure to the inferior and medial orbit to treat a wide variety of pathologies. We describe a comprehensive step-by-step curriculum directed to any audience willing to master this endoscopic skull base approach.

Abstract The complex and dynamic system of fluid flow through the perivascular and interstitial spaces of the CNS has new-found implications for neurological diseases. CSF movement throughout the CNS parenchyma is more dynamic than could be explained via passive diffusion mechanisms alone. Indeed, a semistructured glial-lymphatic (glymphatic) system of astrocyte-supported extracellular perivascular channels serves to directionally channel extracellular fluid, clearing metabolites and peptides to optimize neurological function. Clinical studies of the glymphatic network have to date proven challenging, with most data gleaned from rodent models and post-mortem investigations. However, increasing evidence suggests that disordered glymphatic function contributes to the pathophysiology of CNS ageing, neurodegenerative disease and CNS injuries, as well as normal pressure hydrocephalus. Unlocking such pathophysiology could provide important avenues towards novel therapeutics. We here provide a multidisciplinary overview of glymphatics and critically review accumulating evidence regarding its structure, function and hypothesized relevance to neurological disease. We highlight emerging technologies of relevance to the longitudinal evaluation of glymphatic function in health and disease. Finally, we discuss the translational opportunities and challenges of studying glymphatic science.

Objective: Contour irregularities in the temporal region have been reported previously after procedures involving temporal dissection. In this study, we report paradoxical temporal enlargement (PTE) following interfascial pterional craniotomy. Methods: A retrospective review of patients who underwent a unilateral transcranial procedure with frontotemporal approach at our institution between September 2013 and December 2017 was performed. Patients with a previous craniotomy or bilateral craniotomy were excluded. Radiological imaging series including computed tomography and magnetic resonance imaging were utilized to calculate temporal soft tissue volumes both preoperatively and postoperatively by using advanced software technology. Relative soft tissue volume differences between the operative side and the contralateral side were calculated at different time-points including preoperative, 3-months follow-up (3M), 12-months (12M) follow-up, and the last follow-up (LFU, over 1-year). Results: Forty-three patients were included. Mean age was 52.7 ± 4.5 years. Mean follow-up was 27.9 ± 15.8 months. Significant changes of temporal fat pad relative-volume difference were observed between the preoperative and the corresponding 3M (t [82] = −2.8865, P = 0.0050); 12M (t [77] = −4.4321, P < 0.0001), and LFU (t [74] = −4.9862, P < 0.0001) postoperative time points. No significant change of the temporalis muscle was observed between the preoperative and the corresponding 3M (P = 0.3629), 12M (P = 0.1553), or LFU (P = 0.0715). Soft tissue volume showed a significant increase on the operative side between the preoperative and the corresponding LFU (t [74] = −2.5866, P = 0.0117). Conclusions: Paradoxical temporal enlargement with more than 10% volumetric change was observed in 24% of the patients at their LFU (>1-year). This change was not due to temporalis muscle changes. Paradoxical temporal enlargement was due to hypertrophy of the superficial temporal fat pad. Before surgical correction of postoperative temporal contour changes, it is important to obtain imaging and characterize the etiology of the deformity.

Abstract BACKGROUND AND IMPORTANCE Progressive episodic spells of altered levels of consciousness, often advancing to include paroxysmal autonomic instability, may be indicative of a diencephalic dysfunction underlying spontaneous intracranial hypotension (SIH). A rare, and often indolent, etiology may be spinal cerebrospinal fluid (CSF) leak—an elusive diagnosis, especially in cases of CSF-venous fistula (CVF) that are often missed on routine computed tomography (CT) myelography and magnetic resonance imaging (MRI). CLINICAL PRESENTATION We report an unusual case of a 50-yr-old woman who presented with rapidly progressive cyclical, self-resolving episodes of altered mentation and decreased arousal later in the day. Scrutiny of serial brain MRIs led to a diagnosis of SIH, with severe downward diencephalic and brain stem displacement—resulting in cerebral aqueduct occlusion with obstructive hydrocephalus. Initial clinical improvement occurred with CSF diversion, but the patient quickly deteriorated—developing diencephalic spells, including extensor posturing and severely depressed levels of consciousness. Clinical improvement was seen with stopping CSF diversion and Trendelenburg-positioning. After intensive spinal imaging, dynamic CT myelography identified a left T10 nerve root diverticula and CSF-venous fistula. Surgical obliteration resulted in rapid, profound neurological improvement, and ultimately full neurological recovery by 1 yr. CONCLUSION In our patient, worsening episodes of confusion, postural headaches, and autonomic instability developed due to SIH, which induced profound downward displacement and compression of the diencephalon and brain stem, and accompanied by subsequent obstructive hydrocephalus. Diagnostic persistence identified the CVF, which had caused the complex multifold pathophysiology and clinical presentation. If suspicion remains high for CVF, persistent spinal imaging, particularly with dynamic myelography, may be crucial.

Abstract Objective Cerebrovascular complications (CVC) are rare consequences of vestibular schwannoma (VS) surgery. Our objective was to assess incidences of findings suggestive of postoperative CVC in a large single surgeon cohort, as well as potential risk factors, and implications. Study Design A cohort of 591 patients was retrospectively reviewed. Postoperative magnetic resonance images were screened for findings suggestive of stroke, T2 hyperintensity in the cerebellopontine angle structures or new encephalomalacia. Clinical records were queried for findings consistent with postoperative CVC. Results In total, 61 patients had radiographic findings consistent with possible postoperative CVC (10%); of them, eight had documented intraoperative vascular injury (1.4%), and four had postoperative clinical exam changes indicative of CVC (0.7%). Clinically manifest intraoperative vascular injuries occurred in four patients and involved the petrosal venous complex (n = 3, 5%) or anterior inferior cerebellar artery (n = 1, 2%); clinical deficits included hemiparesis (n = 1, 2%), facial anesthesia (n = 2, 4%), dysphagia (n = 2, 2%), and unfavorable facial nerve function in two (50%). Three out of four patients in this group required out-of-home placement (75%). Clinical CVCs (n = 4) were not significantly associated with tumor size, tumor cyst, gross total resection, or length of stay. Patients with clinical CVC were significantly more likely to require posthospitalization rehabilitation (19 vs. 75%, p = 0.02; 14 vs. 100%, p = 0.0002). Conclusion Although radiographic findings suggestive of CVC were unexpectedly common in this cohort, intraoperative vascular injury and postoperative clinical CVC were exceedingly rare. The association between unfavorable facial nerve outcome and clinical CVC is likely a marker for more difficult operations, predisposing to higher risk of complications.

A 25-year-old man presented with left-sided hearing loss, blurred vision and papilloedema. Imaging revealed a large, left-sided, contrast-enhancing cerebellopontine mass causing obstructive hydrocephalus, consistent with vestibular schwannoma (VS). Following an incomplete resection via retrosigmoid craniotomy at an outside facility, he was referred to our department, and cerebrospinal fluid diversion followed by repeat resection was recommended. A subtotal resection was achieved, and the patient was subsequently treated with adjuvant stereotactic radiosurgery (SRS). Progressive interval growth was observed on serial post-SRS MRI studies; correspondingly, at 31 months after treatment, the patient was initiated on antiprogrammed-death receptor 1 (PD-1) antibody treatment with pembrolizumab. Growth arrest was noted on subsequent serial imaging studies, which have been maintained for a total of 30 months since initiation of a 18-month anti-PD-1 course of therapy. Additional case accumulation and translational study is required to better characterise this therapeutic strategy; however, PD-1/programmed death-ligand 1 inhibition may offer a promising salvage therapy for refractory VS.

Abstract BACKGROUND Vestibular schwannomas (VS) have a peak incidence in the sixth and seventh decades of life. Stereotactic radiosurgery is often the preferred treatment for VS among patients of advanced age. The fraction of elderly patients potentially requiring consideration for surgical treatment is anticipated to expand, mandating an update to management paradigms in this population. OBJECTIVE To describe our experience with surgical management of VS in patients aged 75 yr and older. METHODS Cohort study of all patients aged ≥75 yr with sporadic VS requiring surgical treatment at our institution between 1999 and 2020. Data included preoperative baseline characteristics and outcome data including extent of resection, facial nerve and hearing status, functional outcome, length of stay, and complications. RESULTS A total of 24 patients were included, spanning an age range of 75 to 90 yr. Average tumor size was 2.76 ± 1.04 cm, and average baseline Modified 5-item Frailty Index (mFI-5) score was 1.08 ± 0.93. Extent of resection was gross total in 5 (20.8%), near total in 3 (12.5%), and sub-total resection in the remaining 16 (66.7%). One patient died in the postoperative period because of an acute sub-dural hematoma. Favorable facial nerve function (HB1-2) was preserved in 12 patients (75%) between 75 and 79 yr and 2 patients (28.6%) aged ≥ 80 yr. No cerebrospinal fluid leak or surgical site infection was observed; 3 patients developed hydrocephalus requiring ventriculo-peritoneal shunt placement. Nine patients required out-of-home disposition; all patients eventually returned to independent living. CONCLUSION Microsurgical resection of VS can be safely undertaken in patients greater than 75 y/o but may carry an increased risk of poor facial function.