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Objectives Two pilot studies of AR‐42, a pan‐histone deacetylase inhibitor, in human neurofibromatosis type 2 (NF2), vestibular schwannomas (VS), and meningiomas are presented. Primary endpoints included safety, and intra‐tumoral pharmacokinetics (PK) and pharmacodynamics (PD). Methods Pilot 1 is a subset analysis of a phase 1 study of AR‐42 in solid tumors, which included NF2 or sporadic meningiomas. Tumor volumes and treatment‐related adverse events (TRAEs) are reported (NCT01129193). Pilot 2 is a phase 0 surgical study of AR‐42 assessing intra‐tumoral PK and PD. AR‐42 was administered for 3 weeks pre‐operatively. Plasma and tumor drug concentrations and p‐AKT expression were measured (NCT02282917). Results Pilot 1: Five patients with NF2 and two with sporadic meningiomas experienced a similar incidence of TRAEs to the overall phase I trial. The six evaluable patients had 15 tumors (8 VS, 7 meningiomas). On AR‐42, tumor volume increased in six, remained stable in eight, and decreased in one tumor. The annual percent growth rate decreased in eight, remained stable in three, and increased in four tumors. Pilot 2: Four patients with sporadic VS and one patient with meningioma experienced no grade 3/4 toxicities. Expression of p‐AKT decreased in three of four VS. All tumors had higher AR‐42 concentrations than plasma. Conclusions AR‐42 is safe. Tumor volumes showed a mixed response, but most slowed growth. On a 40‐mg regimen, drug concentrated in tumors and growth pathways were suppressed in most tumors, suggesting this may be a well‐tolerated and effective dose. A phase 2 study of AR‐42 for NF2‐associated tumors appears warranted. Level of Evidence 1b, 4.

Meningioangiomatosis is a rare benign lesion involving the central nervous system. Radiographic appearance can be highly variable which makes pre-operative diagnosis difficult. In this report, we describe meningioangiomatosis in a previously healthy 17-year-old woman who presented with seizures and continued headache and dizziness. This patient presented with a predominately calcified lesion on imaging and eventually underwent near total resection. Meningioangiomatosis is difficult to preoperatively identify, but is an important consideration as prognosis with surgical resection is typically good.

While magnetic resonance imaging (MRI) is superior to computed tomography (CT) in the evaluation of brain neoplasms, it remains important for physicians to be aware that CT, being the typical initial imaging modality for patients with neurologic complaints, can often delineate findings that suggest and potentially characterize a neoplastic process. In patients with oligodendroglioma, CT may allow physicians to suspect this specific neoplasm, even prior to obtaining an MRI examination. For example, striking calcifications within a suspected neoplastic lesion are a dominant feature of oligodendroglioma, more so than with other neoplastic lesions in the brain. This chapter reviews how CT can be a useful tool in patients with this type of brain tumor, whether the setting is CT imaging upon initial presentation, or in patients for whom MRI is contraindicated.

Intracranial hypotension and cerebrospinal fluid (CSF) leaks may occur secondary to numerous pathologies, including trauma, iatrogenic injury, or even in a spontaneous manner. A diagnostic hallmark of intracranial hypotension is the presence of low CSF volume rather than low CSF pressure. As such, intracranial hypotension may occur in the setting of low, normal, or elevated intracranial pressure. The diagnostic evaluation of this pathology, in addition to localization of a potential leak, can be challenging, requiring numerous noninvasive and invasive imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI), lumbar puncture, myelography, or cisternography. While medical management can provide symptomatic relief, definitive treatment of the source of the pathology depends on the etiology of the CSF leak. Depending on the source and localization of the CSF leak, less invasive means of CSF diversion may be sufficient, or patients may require definitive repair of the CSF fistula. Ultimately, proper evaluation and correct diagnosis of the pathology driving the CSF leak frame the paradigm for treatment of intracranial hypotension.

The Prolyse in Acute Cerebral Thromboembolism II (PROACT II) trial showed improved outcomes in patients with proximal middle cerebral artery (MCA) occlusions treated with intra-arterial (IA) thrombolysis within 6 h of stroke onset. We analyzed outcomes of patients with proximal MCA occlusions treated within 3 h of stroke onset in order to determine the influence of time-to-treatment on clinical and angiographic outcomes in patients receiving IA thrombolysis. Thirty-five patients from three academic institutions with angiographically demonstrated proximal MCA occlusions were treated with IA thrombolytics within 3 h of stroke onset. Outcome measures included outcomes at 30–90 day follow-up, recanalization rates, incidence of symptomatic intracranial hemorrhage, and mortality in the first 90 days. The endpoints were compared to the IA treated and control groups of the PROACT II trial. The median admission National Institutes of Health Stroke Scale (NIHSS) score was 16 (range 4–24). The mean time to initiation of treatment was 106 min (range 10–180 min). Sixty-six percent of patients treated, had a modified Rankin Scale (mRS) score of 2 or less at 1–3 month follow-up compared to 40% in the PROACT II trial. The recanalization rate was 77% (versus 66% in PROACT II). The symptomatic intracranial hemorrhage rate was 11% (versus 10% in PROACT II) and the mortality rate was 23% (versus 25% in PROACT II). Time-to-treatment is just as important in IA thrombolysis as it is in IV thrombolysis, both for improving clinical outcomes and recanalization rates as well.

The incidence of primary central nervous system lymphoma (PCNSL) has increased over the past several decades. The prevalence continues to remain higher in the immunocompromised than immunocompetent population. Despite advances in therapy, the prognosis remains poor with PCNSL. Early diagnosis and initiation of appropriate therapy is important for the long-term prognosis. Clinical presentations are variable, and neuroimaging plays a key role in suggesting the diagnosis. Computed tomography generally demonstrates iso- or hyperdense masses that homogeneously enhance. On magnetic resonance imaging, which is the study of choice, the lesions are typically iso- or hypointense on T1 and T2 sequences, and again enhance with contrast. The lesions may also demonstrate restricted diffusion on diffusion-weighted imaging, due to their dense cellularity. The cerebral hemispheres are the most common location, but the deep gray matter and corpus callosum are also frequently involved. Imaging patterns vary between immunocompetent and immunocompromised patients, with the latter group more likely to have multiple lesions and ring enhancement patterns related to central necrosis. Alternative imaging modalities may play a role in the diagnosis in certain circumstances. Numerous variations of PCNSL have been described, and are also discussed in this chapter.

The list of differential considerations of lesions of the central skull base is long and includes many common tumors such as meningiomas and metastatic disease, which are discussed elsewhere in this book. In this chapter, we review the differential list of skull base tumors and discuss in more detail chordomas and to a lesser degree chondrosarcomas, two rare malignant lesions that classically involve the skull base. Although magnetic resonance imaging (MRI) has become the examination of choice in evaluation of intracranial tumors, in the skull base, computed tomography (CT) and MRI have complementary roles. CT is better at defining the complex bony anatomy and extent of bony involvement and MRI, because of its superior soft tissue contrast and multiplanar capability, is better at delineating the location, anatomic extension, and defining involvement of adjacent, critical neural, and vascular structures such as the cavernous sinus, optic chiasm, basilar artery and brain stem, for example. Although imaging studies cannot reliably distinguish chordoma from chondrosarcoma or other skull base lesions, defining the location and extent of the lesion are important factors in determining the optimal the surgical approach and in effective treatment planning. This is critical given that radical resection is the key factor in longer survival and improved quality of life.

Lesions of the sellar, parasellar, and suprasellar regions are common and account for up to 20% of all intracranial neoplasms. Of these, pituitary adenomas are the most common in adults, accounting for over 50% of all lesions in this region. Magnetic resonance imaging has become the imaging examination of choice in this region given its multiplanar capabilities, superior soft-tissue contrast and resolution, and lack of beam hardening artifact seen with computed tomography. The other imaging modalities play a more limited role in answering specific questions related to the lesions. Although there is considerable overlap in the imaging characteristics of the many lesions that can occur in this region, we will attempt to identify imaging characteristics of the lesions that are classic and allow for a more accurate preoperative diagnosis. The type, location, and extent of the lesion are important factors in determining the optimal surgical approach and in effective treatment planning.

Slone HW, Blake JJ, Shah R, Guttikonda S, Bourekas EC rimary CNS lymphoma is the confinement of extranodal lymphoma to the CNS. Classically, lymphomas are divided into Hodgkin’s lymphoma and non-Hodgkin’s lymphoma, with a primary extranodal presentation in 5% and 30% of cases, respectively. With an increasing incidence in both the immunocompetent and immunocompromised populations, primary CNS lymphoma represents 1% of all lymphomas and as many as 16% of all primary brain tumors [1]. This amplified prevalence makes primary CNS lymphoma an important consideration in the differential diagnosis of brain lesions. This pictorial essay will review the varied CT and MRI appearances of intracranial lymphomas.

Gunshot wounds of the head commonly are encountered in the practice of emergency radiology. Radiologists play a vital role in the initial evaluation of patients who present after a gunshot injury and can guide the neurosurgeon's approach to surgery and the forensic pathologist's collection of evidence. It is useful to understand the ballistics that influence missile course and would potential for accurate assessment of injury patterns that occur in gunshot wounds to the head. Additionally, it is imperative to recognize important prognostic findings on computed tomographic imaging to ensure optimal management of the patient.

Purpose: The purpose of this study was to determine the precise in situ location of the lingual nerve in the third molar region using high-resolution magnetic resonance imaging. Patients and Methods: Ten healthy volunteers (20 sides) with mandibular third molars underwent bilateral axial and coronal high-resolution magnetic resonance imaging (MRI) examinations of the posterior mandible and floor of the mouth from the lingula to the mental foramen. Three trained individuals made measurements of each image to determine the vertical and horizontal position of the lingual nerve in the third molar region. Results: The mean vertical (2.75 ± 0.97 mm [range, 1.52–4.61]) and horizontal (2.53 ± 0.67 mm [range, 0.00–4.35]) distances to the lingual crest and lingual plate of the mandible were determined. In the third molar region, there were only 2 of 20 cases (10%) in which the nerve was above the lingual crest, and there were 5 of 20 instances (25%) in which the nerve was in direct contact with the lingual plate. Conclusions: This study precisely documents the in situ location of the lingual nerve in the third molar region, and reconfirms the relative vulnerable position of this structure during third molar surgery.

Scedosporium apiospermum is a deadly fungal infection that can infect the central nervous system, particularly in immunocompromised patients. We present two cases of Scedosporium brain abscesses. The first case was fatal and relevant conventional MRI and MR spectroscopy findings are discussed. To our knowledge, this is the first reported case of MR spectroscopy in Scedosporium apiospermum abscesses. In the second case, the patient recovered and conventional MR findings are followed over several months. In the appropriate clinical setting, conventional MR imaging and MR spectroscopy may facilitate diagnosis, earlier initiation of antifungal pharmacotherapy and surgical intervention in this frequently fatal infection.

Tumors of the sellar and junxtasellar regions are common, accounting for in excess of 10–15% of all intracranial tumors [1]. Although the majority of these are benign tumors, mostly pituitary adenomas, they can account for significant morbidity and a shortened life expectancy. Pituitary adenomas are the most common sellar and suprasellar masses in adults, with meningiomas being the second most common. In children, craniopharyngiomas and chiasmatic/hypothalamic gliomas account for the vast majority of lesions in this region. Adenomas, meningiomas, craniopharyngiomas, chiasmatic/hypothalamic gliomas, and aneurysms account for 75% of sellar and junxtasellar masses [2]. Although the focus of our discussion is tumors, some nonneoplastic entities are discussed, since these can be difficult to distinguish from tumors and must be differentiated, since the treatment approach can be very different.

Diffuse large B-cell lymphoma of the meninges is a particularly rare form of primary CNS lymphoma. We report a case of a 63-year-old woman found to have primary meningeal lymphoma (PML) with dural and leptomeningeal involvement whom we treated with multiple cycles of intra-arterial (IA) methotrexate, intravenous (IV) etoposide phosphate, and IV cyclophosphamide after reversible osmotic blood-brain barrier disruption (BBBD). Improvement was evident on gadolinium-enhanced brain MRI one month into therapy. At 67 months post-diagnosis there is no evidence of CNS disease. After completing her therapy regimen, she remained disease-free for 34 months, when stage IV diffuse large B-cell lymphoma was discovered in her left adrenal gland and right thigh. Following six cycles of rituximab and CHOP treatment, she is presently in complete remission. IA methotrexate and reversible osmotic BBBD without radiation therapy may be an effective therapy for treating PML.

Objectives We report a rare case of spinal myxopapillary ependymoma metastatic to both internal auditory canals (IACs) and its implications for diagnosing neurofibromatosis type 2 (NF2). Methods We present a detailed clinical history, magnetic resonance imaging (MRI), intraoperative photographs, and histopathologic findings from a patient with bilateral IAC lesions, and review the diagnostic criteria for NF2. Results An 11-year-old boy with surgically resected spinal myxopapillary ependymoma, treated with total spine irradiation for recurrence, later showed bilaterally enhancing IAC lesions on T1-weighted MRI with contrast. The diagnosis of NF2 with bilateral vestibular schwannomas was entertained. Close examination of T2-weighted MRI, however, demonstrated the masses to be isointense to cerebrospinal fluid. This finding raised the possibility of other, more unusual IAC lesions. The patient underwent sequential suboccipital craniotomies for tissue diagnosis, and both IAC lesions were found to be myxopapillary ependymomas. Conclusions This is the youngest reported patient with metastatic myxopapillary ependymoma. Although vestibular schwannomas account for the majority of contrast-enhancing T1-weighted IAC lesions, other uncommon lesions may present in a similar manner. A T2 fast-spin echo screening MRI would have missed this patient's lesions. Therefore, both T1-weighted MRI with or without contrast and T2-weighted MRI may be necessary to distinguish vestibular schwannoma from other, more unusual IAC lesions.

✓ Dermoid cysts are rare, benign, congenital tumors. Most case series thus far have featured intradural tumors. The authors report on a case of an extradural dermoid tumor of the middle cranial fossa with osseous invasion, successfully removed using a left subtemporal extradural approach. The clinical presentation, histological features, radiological findings, and management of this unique case are described.

During intra-arterial (IA) chemotherapy of brain tumors, the initial vessels chosen for infusion are based on the vascular distribution of the tumor as revealed by CT or MR imaging. However, angiography may reveal details of vascular anatomy that require an alteration of the vessel infusion plan. The incidence of infusional alterations and the underlying vascular anatomy involved remains unknown in patients with brain tumors undergoing IA chemotherapy. To evaluate this question, we performed a chart, CT/MRI, and angiography review of brain tumor patients receiving IA chemotherapy. Seventy-eight patients were identified with primary (39) and metastatic (39) brain tumors. The cohort consisted of 40 males and 38 females, with a mean age of 47.8 years. During the course of IA treatment, angiographic review identified 5 patients (6.4%) that required an alteration of the vessel infusion plan. In three cases, angiography demonstrated more substantial perfusion of the tumor from a different arterial supply. In two cases, angiography revealed variations in normal anatomy associated with unexpected tumor perfusion. Careful interpretation of angiography at the initiation of each cycle of IA chemotherapy is very important to verify that the appropriate vessels have been chosen for drug infusion, in order to maximize regional dose intensity. In our series, the angiography results necessitated an alteration of the infusion plan in 6.4% of the patient cohort.