Supratentorial ependymoma, zinc finger translocation-associated fusion positive, with extensive synaptophysin immunoreactivity arising from malignant transformation of clear cell ependymoma: A case report.

Background: We describe a case of a supratentorial ependymoma, zinc finger translocation-associated (ZFTA) fusion positive with extensive synaptophysin immunoreactivity arising from malignant transformation of an ependymoma with clear cell features in a patient with long-term follow-up. Case Description: A 55-year-old woman presented with seizures and ataxia 15 years after an initial resection of a clear cell ependymoma, Grade 2. Imaging demonstrated an enhancing right paracentral mass and the patient underwent biopsy and resection. Microscopic analysis showed regions of the tumor with morphological and immunohistochemical features typical of ependymoma, including perivascular pseudorosettes and focal dot- like epithelial membrane antigen positivity, as well as high-grade features. In addition, the neoplasm contained large nodular regions of clear cells exhibiting extensive synaptophysin immunoreactivity, suggestive of neural differentiation, and only focally positive immunoreactivity for glial markers. Electron microscopy showed poorly formed and ill-defined junctional complexes, but no cilia, microvilli, or dense granules were seen. Molecular profiling revealed the presence of a fusion between ZFTA (previously known as C11orf95) and RELA fusion. Conclusion: We report a case of extensive synaptophysin immunoreactivity in a ZFTA-RELA fusion-positive ependymoma that had undergone malignant transformation from a clear cell ependymoma and has long-term follow-up, contributing to the assessment of prognostic significance of synaptophysin immunoreactivity in supratentorial ependymoma, ZFTA fusion positive.

Cerebral blood flow differences between high- vs low-frequency VNS therapy in the epileptic baboon.

PURPOSE: Cerebral blood flow (CBF) tracks physiological effects of ictal or interictal epileptic discharges (IEDs) and neurostimulation. This study compared CBF changes between high-frequency (HF; 300 Hz) microburst, and standard, low-frequency (LF; 30 Hz) vagal nerve stimulation (VNS) Therapy in 2 baboons with genetic generalized epilepsy (GGE), including one with photosensitivity. METHODS: The baboons were selected based on video recordings and scalp EEG studies. They were both implanted with Sentiva™ 1000 devices capable of stimulating at standard and microburst frequencies. Nine H215O (10-20 mCi) positron emission tomographic (PET) scans were performed each session (two PET sessions acquired for each animal). The baboons were sedated with ketamine, paralyzed, and monitored with scalp EEG. CBF changes were compared between the two modes of stimulation and resting scans in the first study, while in the second, VNS Therapy trials were combined with intermittent light stimulation (ILS) at 25 Hz and compared to CBF changes induced by ILS alone. RESULTS: ILS-associated IED rates were slightly reduced by HF- and LF-VNS Therapies in B1, while spontaneous IEDs were completely suppressed by HF-VNS Therapy in B2. Regional CBF changes were consistent between the two modes of therapy in each baboon, in particular with respect to the activation of the superior colliculus and cerebellum. Neither VNS mode suppressed the photoepileptic response in B1. In B2, IED suppression was associated with bilateral deactivations of the frontal and temporal cortices, cingulate and anterior striatum, as well as bilateral cerebellar activations. CONCLUSIONS: This pilot study reveals similar activation/deactivation patterns between LF- and HF-VNS Therapies, but the most pronounced CBF differences between the two baboons and the two modes of stimulation may have been driven by the suppression of the epileptic network by HF-VNS Therapy in B2. Some therapeutic targets appear to be subcortical, including the putamen, superior colliculus, brainstem nuclei, as well as the cerebellum, all of which modulate corticothalamic networks, which is particularly reflected by CBF changes associated with HF-VNS Therapy. These findings need to be replicated in larger samples and correlated with long-term clinical outcomes.

Cortical responsive neurostimulation in a baboon with genetic generalized epilepsy.

OBJECTIVE: To evaluate the efficacy of cortical responsive neurostimulation (CRN) in a male baboon with epilepsy and with genetic generalized epilepsy (GGE), as well as the alteration of seizure patterns and their circadian rhythms due to treatment. METHODS: The baboon was implanted with two subdural frontoparietal strips, bridging the medial central sulci bilaterally. Electrocorticography (ECoG) data were downloaded daily during a three-month baseline, then every 2-3 days over a five-month treatment period. Long episodes, reflecting ictal or interictal epileptic discharges, were also quantified. RESULTS: Twenty-three generalized tonic-clonic seizures (GTCS) and 2 episodes of nonconvulsive status epilepticus (NCSE) were recorded at baseline (median 8 events/month), whereas 26 GTCS were recorded under treatment (median 5/month). Similarly, daily indices of long episodes decreased from 0.46 at baseline to 0.29 with treatment. Ictal ECoG patterns and the circadian distribution of GTCS were also altered by RNS therapy. SIGNIFICANCE: This case study provides the proof-of-concept for RNS therapy in the baboon model of GGE. Cortical responsive neurostimulation (CRN) demonstrated a 38% median reduction in GTCS. Distinct ictal patterns were identified, which changed over the treatment period; the circadian pattern of his GTCS also shifted gradually from night to daytime with treatment. Future studies targeting the thalamic nuclei, or combining cortical and subcortical sites, may further improve detection and control of GTCS as well as other generalized seizure types. More broadly, this study demonstrates opportunities for evaluating seizure detection as well as chronic therapeutic interventions over long term in the baboon.

Bilateral amygdala stimulation reduces avoidance behavior in a predator scent posttraumatic stress disorder model.

OBJECTIVE The predator scent model of posttraumatic stress disorder (PTSD) produces prolonged abnormal anxiety and avoidance-like behaviors. Increased basolateral amygdala activity has been shown to correlate with severity of PTSD symptoms in human studies. Modulation of this increased amygdala activity by deep brain stimulation led to improved symptoms in prior studies that used a foot shock model of inducing PTSD. The predator scent model is a different technique that induces long-lasting avoidance behavioral responses by exposing the animal to an inescapable scent of one of its predators. The authors hypothesize that high-frequency stimulation of the bilateral basolateral amygdala will decrease avoidance and anxiety-like behaviors in a predator scent rodent model of PTSD. METHODS Rodents underwent cat urine exposure in a place preference protocol. Avoidance in the place preference paradigm and anxiety-like behavior in the elevated plus maze were measured before and after high-frequency stimulation. RESULTS Predator scent exposure resulted in long-term significant avoidance behavior in rodents. Bilateral stimulation significantly decreased avoidance behavior in rodents compared to no stimulation following predator scent exposure. There were no significant differences in anxiety behaviors on the elevated plus maze between stimulated and unstimulated cohorts. CONCLUSIONS Bilateral stimulation of the basolateral amygdala leads to decreased avoidance behavior compared to controls in a predator scent model of PTSD.

Case of Lumbar Schwannoma Presenting with Isolated Signs and Symptoms of Intracranial Hypertension.

BACKGROUND: Hydrocephalus and intracranial hypertension are rare signs of spinal tumors when presenting in isolation, particularly with benign tumors. CASE DESCRIPTION: Herein reported is a case of a 53-year-old woman who presented with headache, blurry vision, communicating hydrocephalus, and intracranial hypertension. No primary intracranial pathology was identified, and there were no clinical signs or symptoms of intraspinal pathology. Lumbar puncture revealed elevated opening pressure, cerebrospinal fluid protein, and suspected tumor cells in the cerebrospinal fluid, thus prompting spinal imaging. A primary lumbar schwannoma was subsequently determined to underlie her symptoms, which resolved with tumor resection. CONCLUSIONS: Clinical suspicion of spinal pathology should be maintained in patients with unexplained intracranial hypertension, even in the absence of localizing signs of spinal pathology.

Influence of Intracranial Electrode Density and Spatial Configuration on Interictal Spike Localization: A Case Study.

PURPOSE: Poor seizure outcomes after epilepsy surgery often reflect an incorrect localization of the epileptic sources by standard intracranial EEG interpretation because of limited electrode coverage of the epileptogenic zone. This study investigates whether, in such conditions, source modeling is able to provide more accurate source localization than the standard clinical method that can be used prospectively to improve surgical resection planning. METHODS: Suboptimal epileptogenic zone sampling is simulated by subsets of the electrode configuration used to record intracranial EEG in a patient rendered seizure free after surgery. sLORETA and the clinical method solutions are applied to interictal spikes sampled with these electrode subsets and are compared for colocalization with the resection volume and displacement due to electrode downsampling. RESULTS: sLORETA provides often congruent and at times more accurate source localization when compared with the standard clinical method. However, with electrode downsampling, individual sLORETA solution locations can vary considerably and shift consistently toward the remaining electrodes. CONCLUSIONS: sLORETA application can improve source localization based on the clinical method but does not reliably compensate for suboptimal electrode placement. Incorporating sLORETA solutions based on intracranial EEG in surgical planning should proceed cautiously in cases where electrode repositioning is planned on clinical grounds.

Chiari I malformation as a cause of trigeminal neuralgia: case report.

OBJECTIVE: Trigeminal neuralgia (TN) is usually associated with vascular compression of the trigeminal nerve, but some cases are associated with central lesions such as tumors, aneurysms, or arteriovenous malformations. In this article, we report the 19th case of TN associated with Chiari I malformation and review clinical outcomes and pathophysiology. CLINICAL PRESENTATION: A 63-year-old right-handed man initially presented in 1993 with left-sided lancinating facial pain in the V2 distribution of the trigeminal nerve; the pain was triggered by certain movements, tactile stimulation, or a hot shower. Magnetic resonance imaging revealed a Chiari I malformation associated with a syrinx from C1 to C3. INTERVENTION: The patient underwent uncomplicated suboccipital craniectomy, C1 laminectomy, and duraplasty for Chiari decompression. Postoperatively, his pain resolved over a period of 1 year. CONCLUSION: Chiari I malformation has been found to be associated with TN in 19 cases in the English-language literature. In patients refractory to medical treatment, suboccipital decompression leads to resolution of pain in about two-thirds of patients. Potential mechanisms for the pathogenesis of TN in the setting of Chiari I malformation are discussed. Chiari I malformation is important to consider as a rare cause of TN that responds to surgical therapy.

High-resolution three-dimensional microelectrode brain mapping using stereo microfocal X-ray imaging.

Much of our knowledge of brain function has been gleaned from studies using microelectrodes to characterize the response properties of individual neurons in vivo. However, because it is difficult to accurately determine the location of a microelectrode tip within the brain, it is impossible to systematically map the fine three-dimensional spatial organization of many brain areas, especially in deep structures. Here, we present a practical method based on digital stereo microfocal X-ray imaging that makes it possible to estimate the three-dimensional position of each and every microelectrode recording site in "real time" during experimental sessions. We determined the system's ex vivo localization accuracy to be better than 50 microm, and we show how we have used this method to coregister hundreds of deep-brain microelectrode recordings in monkeys to a common frame of reference with median error of <150 microm. We further show how we can coregister those sites with magnetic resonance images (MRIs), allowing for comparison with anatomy, and laying the groundwork for more detailed electrophysiology/functional MRI comparison. Minimally, this method allows one to marry the single-cell specificity of microelectrode recording with the spatial mapping abilities of imaging techniques; furthermore, it has the potential of yielding fundamentally new kinds of high-resolution maps of brain function.

Multiple pilocytic astrocytomas of the cerebellum in a 17-year-old patient with neurofibromatosis type I.

OBJECTIVE: Approximately 10% of patients with neurofibromatosis I (NFI) patients will have central nervous system (CNS) tumors. The most common of these are hypothalamic-optic gliomas, followed by brainstem and cerebellar pilocytic astrocytomas. While isolated pilocytic astrocytomas in NFI are well described, the appearance of multiple pilocytic astrocytomas in an individual patient is less common. The most frequent combination in NFI patients with more than one pilocytic astrocytoma is optic tract/hypothalamic and brainstem. Other combinations are exceedingly rare; multiple pilocytic astrocytomas have only been reported once in the cerebral hemispheres in a patient with NFI. This report presents the first documented case, to our knowledge, of multiple pilocytic astrocytomas in the cerebellum of a patient with NF1. METHODS: Case report. CONCLUSION: The finding of multiple cerebellar pilocytic astrocytomas in a patient with NF1 is important because it expands the spectrum of presentations for patients with NF1 and also highlights specific diagnostic and therapeutic challenges faced by the treating physicians. The genetic and molecular basis of NF1 is reviewed. Strategies of diagnosis and treatment outlined here are relevant to both patients with NF1 and all patients with multiple posterior fossa tumors.

The diagnostic utility of brain biopsy procedures in patients with rapidly deteriorating neurological conditions or dementia.

OBJECT: Obtaining brain biopsy specimens is often the diagnostic test of last resort for patients with unexplained neurological conditions, particularly those with a rapidly deteriorating neurological course. The goals of this analysis were to determine the diagnostic sensitivity of brain biopsy specimens in these types of patients and retrospectively identify features of these disorders that may have enabled an earlier diagnosis, which may prevent the need for diagnostic brain biopsy procedures in the future. METHODS: The authors reviewed the case records of all brain biopsy procedures that had been performed at a single tertiary care institution between January 1993 and April 2002 in 171 patients. Patients with HIV or nonlymphomatous brain tumors were excluded from this analysis because the utility of brain biopsy specimens for these conditions has been determined front previous studies. A subgroup analysis of this cohort was performed in the 64 patients who had comprehensive medical records and a clinical syndrome involving a progressively deteriorating neurological condition of less than 1 year in duration. The overall sensitivity of brain biopsy procedures for diagnostic purposes in the cohort was 65% (111 of 171 patients). The two most common diagnoses in the subgroup with rapidly deteriorating neurological conditions were primary central nervous system (CNS) B-cell lymphoma in 20.3% (13 patients) and Creutzfeldt-Jakob disease in 15.6% (10 patients), followed by viral encephalitis in 14.1% (nine patients) and CNS vasculitis in 9.4% (six patients). Clinical symptoms and laboratory data were compared among the diagnostic groups. CONCLUSIONS: These results will help guide the evaluation of patients with neurological conditions that are difficult to diagnose and will provide a foundation for further prospective studies.