Spectrum of Surgically Resected Lesions of the Cavernous Sinus: A Neuropathologic Audit.

Background The cavernous sinus is a complex space composed of extradural venous plexus within dural folds. Several important structures like the carotid artery, cranial nerves, and sympathetic nerve fibers traverse through this space. Radiological diagnosis may not be definitive and in the context of discordance between clinical and neuroimaging diagnosis, histopathological evaluation becomes essential for diagnosis and management. Literature on the pathological spectrum of lesions is scarce as, with a shift in the treatment paradigm, most small lesions of cavernous sinus are treated with radiosurgery. However, surgical management still plays a role for larger lesions and in radiologically ambiguous cases for planning the definitive management. Materials and Methods We retrospectively reviewed all surgically resected lesions of the cavernous sinus over the last two decades (1998-2019). The clinical presentation, neuroimaging features, and histopathological findings were reviewed. Lesions extending from sella and other adjacent areas were excluded. Results Thirty-eight cases of isolated cavernous sinus mass lesions were diagnosed over the last two decades (1998-2019). Cavernous hemangiomas (19 cases, 50%) constituted the most frequent pathology, followed by aspergilloma, meningioma, schwannoma, metastatic adenocarcinoma, chondrosarcoma, and chordoma. Overall, 29.4% (10/34) could not be accurately diagnosed on neuroimaging. Of these, four cases of cavernous hemangiomas were mistaken for either meningioma (three cases) or schwannoma (one case). Neither chordoma nor chondrosarcoma was suspected. Conclusion This is the first study in literature, enumerating the pathological and imaging spectrum of surgically resected cavernous sinus lesions. Cavernous hemangiomas, metastases and chordomas, and chondrosarcoma posed the greatest difficulty in diagnosis on neuroimaging and the reasons for the same are analyzed. In the context of clinical and neuroimaging discordance in diagnosis, pathological characterization becomes essential for appropriate and timely management.

Role of Nimodipine and Milrinone in Delayed Cerebral Ischemia.

OBJECTIVE: The role of nimodipine and milrinone in the management of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) was studied using clinical and TCD (transcranial Doppler) parameters. METHODS: In this prospective observational study, patients with DCI after aneurysmal SAH presenting between November 2020 and June 2021 who were treated by either intra-arterial nimodipine (IAN) or intravenous milrinone (IVM) were included after excluding patients in whom both IAN and IVM had been given or mechanical angioplasty was performed. Twelve-hourly TCD was performed during the course of the therapy. Clinical improvement and the development of new brain infarcts were also assessed. A P value <0.05 was considered statistically significant. RESULTS: Thirty-four patients fulfilled the inclusion criteria (IVM, 13/34 [38%]; IAN, 21/34 [62%]); patients in the IVM group (vs. IAN group) had poorer median Glasgow Coma Scale score (12 vs. 13), poorer motor response (

"Trapped labelled spins"-related signal on arterial spin labelling in the assessment of flow-diverted aneurysms: preliminary experience.

PURPOSE: To investigate ASL-MRI features of flow-diverted aneurysms, review their haemodynamic surrogates, and discuss their pertinent clinical implications. METHODS: Retrospective single institutional analysis was performed on the clinical and imaging data of patients who underwent digital subtraction angiography (DSA) and ASL-MRI after endovascular flow diversion for cerebral aneurysms. Pseudo-continuous ASL-MRI was performed with post-label delays of 1525-1800 ms. Intra-aneurysmal "trapped labelled spins" (TLS)-related hypersignal, as seen on cerebral blood flow (CBF)-weighted maps of ASL-MRI, was investigated. Intermodality equivalence with DSA [O'Kelly-Marotta (OKM) grading for occlusion], 3D-TOF-MRA, and 3D spin-echo T1-weighted ("black-blood") images was assessed. RESULTS: Ten cases were included. "TLS" signal was demonstrable in 7/8 (87.5%) of the DSA-visible flow-diverted aneurysms (OKM grade B3, n = 6; OKM grade A3, n = 2). No TLS was seen in both OKM-D (excluded) aneurysms. TLS was not visualised in an OKM-B3 aneurysm with < 3 mm opacifying remnant. 3D-TOF-MRA and ASL-MRI were discordant at 5 instances (45.4%; TOF-MRA false negative, n = 4; false positive, n = 1). Loss of flow void on black-blood images corresponded to the absence of TLS and vice versa in all cases but one. CONCLUSION: "Trapped labelled spins"-related signal on ASL-MRI occurs in patent large aneurysms that have undergone successful endovascular flow diversion. This phenomenon likely represents an interplay of a multitude of haemodynamic factors including decelerated intra-aneurysmal inflow and outflow restriction. Serial intra-saccular TLS signal changes may hold diagnostic value, including contexts where 3D-TOF-MRA interpretation becomes dubious. "Trapped labelled spins"-related signal as a non-invasive proxy marker of aneurysm patency can possibly obviate unnecessary DSA.

Intermittent theta burst stimulation of cerebellar vermis enhances fronto-cerebellar resting state functional connectivity in schizophrenia with predominant negative symptoms: A randomized controlled trial.

OBJECTIVE: Negative symptoms of schizophrenia are substantially disabling and treatment resistant. Novel treatments like repetitive transcranial magnetic stimulation (TMS) need to be examined for the same using the experimental medicine approach that incorporates tests of mechanism of action in addition to clinical efficacy in trials. METHODS: Study was a double-blind, parallel, randomized, sham-controlled trial recruiting schizophrenia with at least a moderate severity of negative symptoms. Participants were randomized to real or sham intermittent theta burst stimulation (iTBS) under MRI-guided neuro-navigation, targeting the cerebellar vermis area VII-B, at a stimulus intensity of 100% active motor threshold, two sessions/day for five days (total = 6000 pulses). Assessments were conducted at baseline (T0), day-6 (T1) and week-6 (T2) after initiation of intervention. Main outcomes were, a) Scale for the Assessment of Negative Symptoms (SANS) score (T0, T1, T2), b) fronto-cerebellar resting state functional connectivity (RSFC) (T0, T1). RESULTS: Thirty participants were recruited in each arm. Negative symptoms improved in both arms (p < 0.001) but was not significantly different between the two arms (p = 0.602). RSFC significantly increased between the cerebellar vermis and the right inferior frontal gyrus (pcluster-FWER = 0.033), right pallidum (pcluster-FWER = 0.042) and right frontal pole (pcluster-FWER = 0.047) in the real arm with no change in the sham arm. CONCLUSION: Cerebellar vermal iTBS engaged a target belonging to the class of cerebello-subcortical-cortical networks, implicated in negative symptoms of schizophrenia. However, this did not translate to a superior clinical efficacy. Future trials should employ enhanced midline cerebellar TMS stimulation parameters for longer durations that can potentiate and translate biological changes into clinical effects.

DREZotomy in the management of post brachial plexus root avulsion neuropathic pain: fMRI correlates for pain relief.

BACKGROUND: Deafferentiation pain following brachial plexus root avulsion has been documented to be severe enough to affect activities of daily living in patients. Microsurgical DREZotomy is known to alleviate the symptoms by decreasing the afferent signals transmitted from the spinal cord to sensory cortex. OBJECTIVES: To document and analyse the effectiveness of DREZotomy and to evaluate the role of 'sensory cortex' in the cause and relief of dysesthetic pain, using fMRI. MATERIALS AND METHODS: This was a prospective study conducted between 2010 and 2016 and included all patients who underwent DREZotomy for dysesthetic pain following traumatic brachial plexus injury (TBPI). Patients were evaluated both preoperatively and postoperatively with Visual Analogue Scale(VAS), Hospital Anxiety and Depression score (HADS) and SF36 questionnaire and effectiveness of surgery was assessed. Functional magnetic resonance imaging (fMRI) of the brain in resting state was performed before and after surgery and was also compared with controls. Patients underwent standard microsurgical DREZotomy from C5 to D1. Postoperative assessment was done at 6 weeks and 6 months following surgery. RESULTS: Our series had 18 patients aged between 22 and 63 years. RTA was the most common cause of injury. There was significant decrease in pain at 6 months follow up compared to pre-operative values as assessed by VAS, HADS, SF36 questionnaire. fMRI analysis revealed cluster activations in the sensory, motor cortex and in the right cingulate gyrus in the preoperative group which was higher than in normal controls. In the postoperative group, the size of the resting state activation was significantly reduced. CONCLUSION: DREZotomy is an effective procedure for TBPI patients. We hypothesize that these fMRI findings reflect the cortical reorganization that occurs not only after injury but also following successful surgery which explains the cause and relief of dyesthetic pain.

Anterior Cranial Fossa Dural Arteriovenous Fistulae - Angioarchitecture and Intervention.

PURPOSE: Anterior cranial fossa (ACF) dural arteriovenous fistulae (DAVF) are rare, unique, and ominous. While surgical disconnection is considered as the favored management option, endovascular treatment has lately gained importance. We present a single institution experience of seven cases. METHOD: A retrospective analysis was performed on the institutional patient database. Features analyzed were demographic details, symptoms, angioarchitecture, treatment course, angiographic results, procedural complications, and follow-up. RESULTS: This study included seven patients. The age at presentation ranged from 5-67 years. Clinical symptomatology was as intracranial hemorrhage in 4 patients and headache, chemosis and seizures in one patient each. The fistulae were paramedian at the ACF base. All DAVFs were Cognard type 4. The arterial feeders were from the anterior ethmoidal branches of the ophthalmic artery in all cases (bilateral in n = 5), frontal branches of the middle meningeal artery (MMA) (n = 6), and multiple ECA branches. The arterial route was the choice for access. Complete fistula obliteration was achieved in all but one patient. A traversed vein underwent rupture in one patient. One patient suffered postsurgical hemorrhage. No clinical or angiographic recurrence was noted. CONCLUSION: The DAVFs of the ACF are inherently high-grade lesions. Transorbital ECA-ICA branch anastomoses may be recruited as feeders. They may be best managed by multidisciplinary means personalized on an angioarchitectural basis. Endovascular embolization is safe and efficacious when performed through a navigable feeder from the frontal division of the MMA, which according to our interpretation is in anastomosis with the anterior falcine branch of the anterior ethmoidal artery.

Pial arteriovenous fistula: A clinical and neuro-interventional experience of outcomes in a rare entity.

PURPOSE: Pial arteriovenous fistulae (PAVF) are rare intracranial vascular malformations, predominantly seen in children and distinct from arteriovenous malformations and dural arteriovenous fistulae. PAVF often leads to high morbidity and mortality. The aim of our study was to describe the clinical features and endovascular management of PAVF at various intracranial locations; to analyze the use of liquid embolic agents and coils alone or in combination in the treatment of PAVF and to analyze the outcome of embolization. MATERIALS AND METHODS: Retrospective review of diagnostic angiography and neurointerventional database of our institution identified a cohort of 15 patients with non-galenic PAVF from 2008 to 2014 out of 6750 patients. Fourteen patients were treated endovascularly with coils and liquid embolic materials in combination or alone. Patients were followed up for evaluation of prognosis. RESULTS: Age of the patients ranged from 3 to 37 years. Most patients were male and most common presentation was headache followed by seizure. Most common location of fistula was frontal lobe. The most common type was single artery single hole fistula with venous varix. Satisfactory obliteration was seen in all cases. One patient developed intraparenchymal hematoma on the first post procedural day and outcome was poor. CONCLUSIONS: PAVF are rare intracranial vascular malformations which can effectively be managed endovascularly with liquid embolic, coils alone, or in combination. Complete occlusion of the fistula can be achieved in most cases in a single sitting with a reasonable morbidity related to the procedure, compared with the natural history of this disease.

Effect of Intra-arterial Nimodipine on Cerebral Oxygen Saturation and Systemic Hemodynamic Indices in Patients With Cerebral Vasospasm: A Prospective Cohort Study.

BACKGROUND: Intra-arterial nimodipine (IaN) is used in the management of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). The impact of IaN therapy on regional cerebral oxygen saturation (rScO2) assessed by near infra-red spectroscopy, and dynamic cardiac indices, is currently unknown. This study assessed the effect of IaN on rScO2 and systemic hemodynamic indices during IaN therapy for cerebral vasospasm after aSAH. METHODS: This prospective cohort study was conducted in 20 patients over sixteen month period after ethics committee approval and informed consent. Patients with angiographic evidence of vasospasm received IaN 3mg over 30 minutes in the spastic vessels. Data regarding rScO2 heart rate (HR), mean blood pressure (MBP) cardiac index (CI), stroke volume index (SVI), stroke volume variation (SVV), and total peripheral resistance index (TPRI) were collected during IaN treatment. The primary outcome measure was change in rScO2 after IaN therapy. RESULTS: There was no significant change from baseline in ipsilateral and contralateral rScO2 after IaN administration (mean difference [MD], 0.2; 95% confidence interval [CI], -2.1 to 1.6; P=0.804, and 1.3; -1.1 to 3.8; P=0.276, respectively). There was a significant decrease in MBP and TPRI (MD, -12.4; 95% CI, -6.6 to -18.2; P<0.001, and -674.3; -374.9 to -973.7; P<0.001, respectively) and increase in SVI and CI (MD, 7.5; 95% CI, 14.4 to 0.6; P=0.035 and 0.7; 0.9 to 0.4; P<0.001, respectively) after IaN therapy. HR and SVV were unchanged. CONCLUSIONS: IaN for aSAH-related cerebral vasospasm did not improve rScO2 but was associated with significant systemic hemodynamic effects, including a decrease in MBP and TPRI. These hemodynamic changes might offset any potential effects of IaN to improve rScO2.

Intracranial fungal granuloma: a single-institute study of 90 cases over 18 years.

OBJECTIVE: Intracranial fungal granuloma (IFG) remains an uncommon entity. The authors report a single-institute study of 90 cases of IFG, which is the largest study until now. METHODS: In this retrospective study, all cases of IFG surgically treated in the years 2001-2018 were included. Data were obtained from the medical records and the pathology, microbiology, and radiology departments. All relevant clinical data, imaging characteristics, surgical procedure performed, perioperative findings, and follow-up data were recorded from the case files. Telephonic follow-up was also performed for a few patients to find out their current status. RESULTS: A total of 90 cases consisting of 64 males (71.1%) and 26 (28.9%) females were evaluated. The mean patient age was 40.2 years (range 1-79 years). Headache (54 patients) was the most common presenting complaint, followed by visual symptoms (35 patients), fever (21 patients), and others such as limb weakness (13 patients) or seizure (9 patients). Cranial nerve involvement was the most common sign (47 patients), followed by motor deficit (22 patients) and papilledema (7 patients). The mean duration of symptoms before presentation was 6.4 months (range 0.06-48 months). Thirty patients (33.3%) had predisposing factors like diabetes mellitus, tuberculosis, or other immunocompromised status. A pure intracranial location of the IFG was seen in 49 cases (54.4%), whereas rhinocerebral or paranasal sinus involvement was seen in 41 cases (45.6%). Open surgery, that is, craniotomy and decompression, was performed in 55 cases, endoscopic biopsy was done in 30 cases, and stereotactic biopsy was performed in 5 cases. Aspergilloma (43 patients) was the most common fungal mass, followed by zygomycosis (13 patients), chromomycosis (9 patients), cryptococcoma (7 patients), mucormycosis (5 patients), and candida infection (1 patient). In 12 cases, the exact fungal phenotype could not be identified. Follow-up was available for 69/90 patients (76.7%). The mean duration of the follow-up was 37.97 months (range 3-144 months). The mortality rate was 52.2% (36/69 patients) among the patients with available follow-up. CONCLUSIONS: A high index of suspicion for IFG should exist for patients with an immunocompromised status and diabetic patients with rhinocerebral mass lesions. Early diagnosis, aggressive surgical decompression, and a course of promptly initiated antifungal therapy are associated with a better prognosis.

Precipitating hydrophobic injectable liquid embolization of intracranial vascular shunts: initial experience and technical note.

Precipitating hydrophobic injectable liquid is a new liquid embolic agent used mainly for intracranial neurointervention. The agent is ready to use (no shaking is required), since iodine, the radiopaque material, is covalently bonded into the compound. Additionally, due to the absence of tantalum, minimal artifacts are seen on postprocedure follow-up CT scans, and the agent penetrates into vessels smaller than 10 µm. The authors report their initial experience with the use of this agent in neurovascular intervention.

Transarterial treatment of direct carotico-cavernous fistulas with coils and Onyx.

INTRODUCTION: The purpose of this study was to evaluate the role of combination of liquid embolic agent ethylene vinyl alcohol copolymer (Onyx) and detachable coils in the treatment of direct carotico-cavernous fistulas (CCFs). METHODS: We prospectively collected clinical and radiological data of all patients who underwent embolization of direct CCFs at our institution over a period of 21 months. The clinical parameters, angioarchitecture, presence of cortical venous reflux, volume of Onyx used, number of coils used, extent of embolization and complications were recorded. RESULTS: A total of 21 consecutive patients (18 men and 3 women, 14 to 48 years) with direct CCF underwent embolization with a combination of coils and Onyx. Embolization was done through the arterial route in all cases. Complete obliteration of the fistula was achieved in 19 of 21 cases. Cast embolization in middle cerebral artery occurred in one patient; however, the cast was completely retrieved with Solitaire device, and the patient did not have any neurological deficit. All completely treated patients reported relief of symptoms at varying intervals. At 6-month follow-up, none of the patients with complete occlusion of the fistula showed any recurrence. CONCLUSION: The adjuvant use of Onyx with detachable coils in direct CCF through the arterial route is a safe and effective method for embolization with immediate and complete occlusion of the fistula. To the best of our knowledge, this is the first case series of demonstration of arterial use of Onyx with coils in the treatment of direct CCFs.

Neuropathological correlate of the "concentric target sign" in MRI of HIV-associated cerebral toxoplasmosis.

Cerebral toxoplasmosis is a frequent cause of focal brain lesions in the setting of immunodeficiency states, particularly acquired immune deficiency syndrome (AIDS), and magnetic resonance imaging (MRI) is an important diagnostic modality to differentiate toxoplasmosis from tuberculoma, and primary central nervous system lymphoma with diverse therapeutic implications. Several imaging patterns have been described in cerebral toxoplasmosis. The "concentric target sign" is a recently described MRI sign on T2-weighted imaging of cerebral toxoplasmosis that has concentric alternating zones of hypo- and hyperintensities. It is believed to be more specific than the well-known "eccentric target sign" in the diagnosis of cerebral toxoplasmosis and hence more useful in differentiation from other focal brain lesions in the context of AIDS. The concentric target sign, seen in deep parenchymal lesions, is distinct from the surface-based cortical "eccentric" target sign. The histopathological correlate of the latter has been recently described, but that of the concentric target sign is not known. In this study we describe the neuropathological correlate of this concentric target sign from the postmortem of a 40-year-old man with AIDS-associated cerebral toxoplasmosis. The concentric alternating zones of hypo/hyper/iso/intensities corresponded to zones of hemorrhage/fibrin-rich necrosis with edema/coagulative compact necrosis/inflammation with foamy histiocytes admixed with hemorrhage forming the outermost zone, respectively. The exclusive specificity of this sign in cerebral toxoplasmosis remains to be further elucidated.