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Open access

Alexander D. Rebchuk, Stephano J. Chang, Donald E. G. Griesdale, and Christopher R. Honey

BACKGROUND

Subdural empyema (SDE) is a life-threatening intracranial infection that, without timely surgical intervention and appropriate antibiotic treatment, is inevitably fatal. SDE is classically recognized on brain imaging as a subdural collection surrounded by a contrast-enhancing ring.

OBSERVATIONS

The authors describe the case of a 41-year-old male with clinical features consistent with SDE but without any contrast enhancement on multiple computed tomography scans obtained more than 48 hours apart. Given the high clinical suspicion for SDE, a craniotomy was performed that demonstrated frank pus that eventually grew Streptococcus pyogenes.

LESSONS

This case demonstrates that SDE may present without ring enhancement on contrast-enhanced imaging. In critically ill patients with a high clinical suspicion for SDE despite lack of contrast enhancement, we demonstrate that exploratory burr holes or craniotomy can provide diagnostic confirmation and source control.

Open access

Masasuke Ohno, Shunichiro Kuramitsu, Akari Iwakoshi, Junya Yamaguchi, Fumiharu Ohka, and Ryuta Saito

BACKGROUND

Although the risk of developing malignant lymphoma is higher in patients with rheumatoid arthritis (RA) than in the general population, primary central nervous system lymphoma (PCNSL) in patients with RA is extremely rare. In recent years, there has been concern that biological disease-modifying antirheumatic drugs (bDMARDs), widely administered to patients with RA, might increase the risk of cancer development. The authors report the first case of PCNSL in a patient with RA receiving the bDMARD tocilizumab.

OBSERVATIONS

A 70-year-old man who was diagnosed with RA in 2010 was treated with low-dose methotrexate (MTX) from 2010 to 2015. Tocilizumab was commenced in 2012. In 2018, he developed gait disturbances, and gadolinium-enhanced magnetic resonance imaging showed multiple contrast-enhanced lesions in the basal ganglia and brain stem. Stereotactic brain biopsy led to the diagnosis of diffuse large B-cell lymphoma, and finally PCNSL was diagnosed. He was treated with five courses of MTX 3.5 g/m2, and his disease has been in remission for 34 months.

LESSONS

Low-dose MTX and bDMARDs are associated with the concern of increased cancer risk in patients with RA. Because tocilizumab has been in use for a relatively short time, further accumulation of cases and careful follow-up are necessary.

Open access

Mika Kaneko, Toru Tateoka, Kazuya Kanemaru, Hideyuki Yoshioka, Takuma Wakai, Koji Hashimoto, and Hiroyuki Kinouchi

BACKGROUND

Idiopathic extracranial internal carotid artery vasospasm (IEICAV) is a rare cerebrovascular disorder causing transient or permanent cerebral ischemia. The pathophysiology underlying this disorder is not well understood. Although various medical treatments have been tried, complete remission of vasospasm is difficult to achieve. The first case of bilateral IEICAV induced by head rotation, which was successfully treated by carotid artery stenting (CAS), was presented.

OBSERVATIONS

A 40-year-old woman with bilateral IEICAV had been conservatively treated for 13 years. However, transient ischemic attacks (TIAs) were not suppressed. She eventually presented with a large brain infarction in the left hemisphere and was referred to our department. Digital subtraction angiography clearly demonstrated the triggering of internal carotid artery (ICA) vasospasm by head rotation. After CAS treatment, the TIAs disappeared completely.

LESSONS

Clinicians should recognize that ordinary mechanical stimulation to the ICA by head rotation can induce vasospasm, and CAS should be performed for refractory IEICAV at the appropriate time to avoid cerebral infarction causing severe neurological deficits.

Open access

Bryan A. Schatmeyer, Rakan Dodin, Michael Kinsman, and David Garcia

BACKGROUND

Central neuropathic pain (CNP) of the cervical and/or thoracic spinal cord has many etiologies, both natural and iatrogenic. Frequently, CNP is medically refractory and requires surgical treatment to modulate the perception of pain. Spinal cord stimulation is a modality commonly used in adults to treat this type of refractory pain; however, it is rarely used in the pediatric population.

OBSERVATIONS

The authors reported a case involving a common pediatric condition, Chiari malformation type I with syrinx, that led to a debilitating complex regional pain syndrome. The associated life-altering pain was successfully alleviated following placement of a spinal cord stimulator.

LESSONS

CNP, or the syndromic manifestations of the pain (complex regional pain syndrome), can alter an individual’s life in dramatic ways. Spinal cord stimulator placement in carefully selected pediatric patients should be considered in these difficult pain treatment paradigms.

Open access

Sergi Cobos Codina, Luis Miguel Bernal García, José Antonio Rodríguez Sánchez, Tania Gavilán Iglesias, and Luis Fernández de Alarcón

BACKGROUND

Tentorial dural arteriovenous fistulas (DAVFs) with perimedullary venous drainage causing cervical myelopathy are very uncommon conditions with an extremely aggressive behavior. When the characteristic radiological clues are missing, the unspecific clinical picture may cause delay and make the diagnosis challenging.

OBSERVATIONS

Here the authors report a case of a 58-year-old man who developed progressive spastic tetraparesis and dyspnea with an extensive mild enhancing cervical cord lesion initially oriented as a neurosyphilis-associated transverse myelitis. Acute worsening after steroid administration redirected the diagnosis, and a tentorial Cognard type V DAVF was elicited. The microsurgical disconnection process is described, and previously documented cases in the literature are reviewed.

LESSONS

If a DAVF is highly suspected, it is important to consider the possibility of its intracranial origin, and spinal as well as cerebral arteriography must be performed.

Restricted access

Shunsaku Goto, Takashi Izumi, Masahiro Nishihori, Tasuku Imai, Yoshio Araki, Fumiaki Kanamori, Kenji Uda, Kinya Yokoyama, and Ryuta Saito

OBJECTIVE

The protocol for antiplatelet therapy after stent-assisted coil embolization (SACE) for intracranial aneurysms is not well established. In particular, the indications for single antiplatelet therapy (SAPT) discontinuation remain controversial. The authors investigated the long-term outcomes of SAPT discontinuation after SACE among patients at a single institution.

METHODS

Patients who underwent SACE during the period from 2010 to 2020 and who were followed up for > 1 year were included in this study. The delayed ischemic and hemorrhagic complication rates were examined during follow-up. Moreover, the risk factors of antiplatelet therapy reduction or discontinuation and the outcomes of SAPT discontinuation were examined.

RESULTS

In total, 240 patients were included in the analysis. The average patient age was 60.3 years, and the average follow-up period was 46.7 months. Nine (3.8%) patients presented with symptomatic delayed ischemic complication, and 3 (1.3%) patients experienced a decline in modified Rankin Scale score. The stent configuration (T- or Y-stent) was the only risk factor associated with delayed ischemic complication (p < 0.001). SAPT was discontinued in 147 (71.7%) of 205 patients who were followed up for > 2 years, and no ischemic complications were observed.

CONCLUSIONS

It is safe to discontinue SAPT in patients without ischemic complications and with stable intraaneurysmal signals on MRA 2 years after SACE. The T- or Y-stent is a high-risk factor for delayed ischemic complications, and antiplatelet therapy reduction or discontinuation should be cautiously considered.

Restricted access

Ron Gadot, Nora Vanegas Arroyave, Huy Dang, Adrish Anand, Ricardo A. Najera, Lisa Yutong Taneff, Steven Bellows, Arjun Tarakad, Joseph Jankovic, Andreas Horn, Ben Shofty, Ashwin Viswanathan, and Sameer A. Sheth

OBJECTIVE

Deep brain stimulation (DBS) for Parkinson disease (PD) is traditionally performed with awake intraoperative testing and/or microelectrode recording. Recently, however, the procedure has been increasingly performed under general anesthesia with image-based verification. The authors sought to compare structural and functional networks engaged by awake and asleep PD-DBS of the subthalamic nucleus (STN) and correlate them with clinical outcomes.

METHODS

Levodopa equivalent daily dose (LEDD), pre- and postoperative motor scores on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III), and total electrical energy delivered (TEED) at 6 months were retroactively assessed in patients with PD who received implants of bilateral DBS leads. In subset analysis, implanted electrodes were reconstructed using the Lead-DBS toolbox. Volumes of tissue activated (VTAs) were used as seed points in group volumetric and connectivity analysis.

RESULTS

The clinical courses of 122 patients (52 asleep, 70 awake) were reviewed. Operating room and procedure times were significantly shorter in asleep cases. LEDD reduction, MDS-UPDRS III score improvement, and TEED at the 6-month follow-up did not differ between groups. In subset analysis (n = 40), proximity of active contact, VTA overlap, and desired network fiber counts with motor STN correlated with lower DBS energy requirement and improved motor scores. Discriminative structural fiber tracts involving supplementary motor area, thalamus, and brainstem were associated with optimal clinical improvement. Areas of highest structural and functional connectivity with VTAs did not significantly differ between the two groups.

CONCLUSIONS

Compared to awake STN DBS, asleep procedures can achieve similarly optimal targeting—based on clinical outcomes, electrode placement, and connectivity estimates—in more efficient procedures and shorter operating room times.

Restricted access

Shameer Aslam, Natesan Damodaran, Ramiah Rajeshkannan, Manjit Sarma, Siby Gopinath, and Ashok Pillai

OBJECTIVE

Positron emission tomography (PET) imaging has assumed an essential role in the presurgical evaluation of epileptogenic foci in drug-resistant epilepsy by identifying the hypometabolic cerebral cortex. The authors herein designed a pilot study to test a novel technique of PET asymmetry after anatomical symmetrization coregistered to MRI (PASCOM), utilizing interhemispheric metabolic asymmetry on interictal fluorine 18–labeled fluorodeoxyglucose (FDG)-PET to better localize the epileptogenic zone.

METHODS

The authors analyzed interictal FDG-PET scans from 23 patients with drug-resistant epilepsy, mean (± SD) age 20.9 ± 13.1 years old, who had an Engel class I postsurgical outcome while followed up for > 12 months. T1-weighted and FLAIR MRI were used to create a patient-specific, structurally symmetrical template. The asymmetry index (AI) image was computed to detect the cerebral region of hypometabolism using different z-score threshold criteria to optimize sensitivity and specificity. The detected regions were compared with the resection cavity on postoperative MRI using predefined anatomical labels. PASCOM was compared with the visual analysis of FDG-PET by a nuclear medicine consultant blinded to other clinical data (VIS) and visual analysis during multidisciplinary team discussion (MDT). The efficacy of each technique was compared based on a performance score (S), sensitivity, specificity, and correct lateralization of epileptogenicity.

RESULTS

The mean S was maximum (1.30 ± 1.23) for AI images when thresholded at z > 4 and retaining the cluster of more than 100 voxels containing the peak AI value (Z4C) with 73.03% sensitivity and 96.43% specificity. The mean S was minimum for VIS (0.27 ± 0.31). The mean sensitivity was maximum for MDT (85.04%) and minimum for Z5C (AI images thresholded at z > 5 and clustered; 59.47%), whereas the mean specificity was maximum for Z5C (97.77%) and minimum for VIS (64.60%). Z3C (AI images thresholded at z > 3 and clustered) and Z4C were able to correctly identify the side of epileptogenicity in all the patients.

CONCLUSIONS

The PASCOM technique with a Z4C threshold had a maximum performance score with good sensitivity and specificity in localizing and lateralizing the epileptogenic zone. The described technique outperformed the conventional visual analysis of FDG-PET and hence warrants further prospective verification.

Restricted access

Yi Wang, Maki Sakaguchi, Hemragul Sabit, Sho Tamai, Toshiya Ichinose, Shingo Tanaka, Masashi Kinoshita, Yasuo Uchida, Sumio Ohtsuki, and Mitsutoshi Nakada

OBJECTIVE

An extracellular matrix such as collagen is an essential component of the tumor microenvironment. Collagen alpha-2(I) chain (COL1A2) is a chain of type I collagen whose triple helix comprises two alpha-1 chains and one alpha-2 chain. The authors’ proteomics data showed that COL1A2 is significantly higher in the blood of patients with glioblastoma (GBM) compared with healthy controls. COL1A2 has many different functions in various types of cancers. However, the functions of COL1A2 in GBM are poorly understood. In this study, the authors analyzed the functions of COL1A2 and its signaling pathways in GBM.

METHODS

Surgical specimens and GBM cell lines (T98, U87, and U251) were used. The expression level of COL1A2 was examined using GBM tissues and normal brain tissues by quantitative real-time polymerase chain reaction. The clinical significance of these levels was evaluated using Kaplan-Meier analysis. Small interfering RNA (siRNA) and small hairpin RNA of COL1A2 were transfected into GBM cell lines to investigate the function of COL1A2 in vitro and in vivo. Flow cytometry was introduced to analyze the alteration of cell cycles. Western blot and immunohistochemistry were performed to analyze the underlying mechanisms.

RESULTS

The expression level of COL1A2 was upregulated in GBM compared with normal brain tissues. A higher expression of COL1A2 was correlated with poor progression-free survival and overall survival. COL1A2 inhibition significantly suppressed cell proliferation in vitro and in vivo, likely due to G1 arrest. The invasion ability was notably deteriorated by inhibiting COL1A2. Cyclin D1, cyclin-dependent kinase 1, and cyclin-dependent kinase 4, which are involved in the cell cycle, were all downregulated after blockade of COL1A2 in vitro and in vivo. Phosphoinositide 3-kinase inhibitor reduced the expression of COL1A2. Although downregulation of COL1A2 decreased the protein kinase B (Akt) phosphorylation, Akt activator can phosphorylate Akt in siRNA-treated cells. This finding suggests that Akt phosphorylation is partially dependent on COL1A2.

CONCLUSIONS

COL1A2 plays an important role in driving GBM progression. COL1A2 inhibition attenuated GBM proliferation by promoting cell cycle arrest, indicating that COL1A2 could be a promising therapeutic target for GBM treatment.

Open access

John P. Andrews, Nathan Cahn, Benjamin A. Speidel, Jason E. Chung, Deborah F. Levy, Stephen M. Wilson, Mitchel S. Berger, and Edward F. Chang

OBJECTIVE

Broca’s aphasia is a syndrome of impaired fluency with retained comprehension. The authors used an unbiased algorithm to examine which neuroanatomical areas are most likely to result in Broca’s aphasia following surgical lesions.

METHODS

Patients were prospectively evaluated with standardized language batteries before and after surgery. Broca’s area was defined anatomically as the pars opercularis and triangularis of the inferior frontal gyrus. Broca’s aphasia was defined by the Western Aphasia Battery language assessment. Resections were outlined from MRI scans to construct 3D volumes of interest. These were aligned using a nonlinear transformation to Montreal Neurological Institute brain space. A voxel-based lesion-symptom mapping (VLSM) algorithm was used to test for areas statistically associated with Broca’s aphasia when incorporated into a resection, as well as areas associated with deficits in fluency independent of Western Aphasia Battery classification. Postoperative MRI scans were reviewed in blinded fashion to estimate the percentage resection of Broca’s area compared to areas identified using the VLSM algorithm.

RESULTS

A total of 289 patients had early language evaluations, of whom 19 had postoperative Broca’s aphasia. VLSM analysis revealed an area that was highly correlated (p < 0.001) with Broca’s aphasia, spanning ventral sensorimotor cortex and supramarginal gyri, as well as extending into subcortical white matter tracts. Reduced fluency scores were significantly associated with an overlapping region of interest. The fluency score was negatively correlated with fraction of resected precentral, postcentral, and supramarginal components of the VLSM area.

CONCLUSIONS

Broca’s aphasia does not typically arise from neurosurgical resections in Broca’s area. When Broca’s aphasia does occur after surgery, it is typically in the early postoperative period, improves by 1 month, and is associated with resections of ventral sensorimotor cortex and supramarginal gyri.