Extradural Dumbbell-Shaped Tuberculoma Masquerading as Nerve Sheath Tumor: Case Report and Review of Literature.

BACKGROUND: Spinal tuberculosis has been listed as a rare cause of neuroforaminal widening with only 2 previous reports in the literature. Here, we report the third case of an extradural tuberculoma extending through and expanding the neural foramen closely masquerading as a nerve sheath tumor including, to the best of our knowledge, the first description of magnetic resonance imaging, operative, and histopathology findings. CASE DESCRIPTION: A 65-year-old Nigerian man presented with signs and symptoms of worsening thoracic myeloradiculopathy for the past month. Imaging found an extradural dumbbell-shaped lesion involving the spinal canal, neural foramen, and paraspinal area with a combination of solid and cystic components causing bony remodeling of the pedicle and vertebral body, as well as enlargement of the neural foramen. Surgery was performed to resect the mass, and pathology postoperatively demonstrated caseating granulomas, rare thin elongated organisms on Ziehl-Neelsen staining, and involvement of nerve fascicles. CONCLUSIONS: This case illustrates that a tuberculoma can have many of the features of a benign neoplasm, such as encapsulation, appearance of a slow rate of growth, and development of necrosis or even cystic degeneration. With the specific findings of entrapped nerve fascicles, we postulate that the lesion represents a nerve sheath tuberculoma rather than spinal tuberculosis of the pedicle or posterior elements. Furthermore, only a lesion of the nerve sheath would have the characteristic dumbbell appearance as it extends through the foramen.

Tertiary lymphoid structures in the choroid plexus in neuropsychiatric lupus.

The central nervous system manifestations of systemic lupus erythematosus (SLE) remain poorly understood. Given the well-defined role of autoantibodies in other lupus manifestations, extensive work has gone into the identification of neuropathic autoantibodies. However, attempts to translate these findings to patients with SLE have yielded mixed results. We used the MRL/MpJ-Faslpr/lpr mouse, a well-established, spontaneous model of SLE, to establish the immune effectors responsible for brain disease. Transcriptomic analysis of the MRL/MpJ-Faslpr/lpr choroid plexus revealed an expression signature driving tertiary lymphoid structure formation, including chemokines related to stromal reorganization and lymphocyte compartmentalization. Additionally, transcriptional profiles indicated various stages of lymphocyte activation and germinal center formation. The extensive choroid plexus infiltrate present in MRL/MpJ-Faslpr/lpr mice with overt neurobehavioral deficits included locally proliferating B and T cells, intercellular interactions between lymphocytes and antigen-presenting cells, as well as evidence for in situ somatic hypermutation and class switch recombination. Furthermore, the choroid plexus was a site for trafficking lymphocytes into the brain. Finally, histological evaluation in human lupus patients with neuropsychiatric manifestations revealed increased leukocyte migration through the choroid plexus. These studies identify a potential new pathway underlying neuropsychiatric lupus and support tertiary lymphoid structure formation in the choroid plexus as a novel mechanism of brain-immune interfacing.

Hemorrhagic intracranial follicular dendritic cell sarcoma: A case report.

BACKGROUND: Follicular dendritic cell (FDC) sarcoma is an extremely rare neoplasm, which has only been reported once in the literature with an intracranial occurrence. Neither hemorrhagic presentation of an intracranial instance of FDC sarcoma nor its rapid recurrence has yet been published in the literature. CASE DESCRIPTION: We report the case of a 61-year-old female who presented with confusion and headaches secondary to a right frontal hemorrhagic lesion, and her subsequent presentations for recurrence of the lesion and finding of a new intracranial lesion. Immunohistopathologic analysis confirmed the diagnosis based on immunoreactivity for clusterin and CD 35. CONCLUSION: As demonstrated in this case report, the presentation and progression of primary intracranial follicular dendritic cell sarcoma can often be misleading, and consideration for this rare entity should be made in cases of hemorrhagic dural-based lesions without a primary source of malignancy.

Glioblastoma multiforme presenting with an open ring pattern of enhancement on MR imaging.

BACKGROUND: Intracerebral ring enhancing lesions can be the presentation of a variety of pathologies, including neoplasia, inflammation, and autoimmune demyelination. Use of a precise diagnostic algorithm is imperative in correctly treating these lesions and minimizing potential adverse treatment effects. CASE DESCRIPTION: A 55-year-old patient presented to the hospital with complaints of a post-concussive syndrome and a non-focal neurologic exam. Imaging revealed a lesion with an open ring enhancement pattern, minimal surrounding vasogenic edema, and minimal mass effect. Given the minimal mass effect, small size of the lesion, and nonfocal neurological exam, we elected to pursue a comprehensive noninvasive neurologic workup because our differential ranged from inflammatory/infectious to neoplasm. Over the next 8 weeks, the patient's condition worsened, and repeat imaging showed marked enlargement of the lesion with a now closed ring pattern of enhancement with satellite lesions and a magnetic resonance (MR) spectroscopy and perfusion signature suggestive of neoplasm. The patient was taken to surgery for biopsy and debulking of the lesion. Surgical neuropathology examination revealed glioblastoma multiforme. CONCLUSION: The unique open ring enhancement pattern of this lesion on initial imaging is highly specific for a demyelinating process, however, high-grade glial neoplasms can also present with complex and irregular ring enhancement including an open ring sign. Therefore, other imaging modalities should be used, and close follow-up is warranted when the open ring sign is encountered.

Dermatomyositis and HIV.

HIV has been linked to several autoimmune disorders since its emergence in the 1980s. By affecting different cells and pathways in the immune system, HIV induces the development of certain autoimmune diseases while prohibiting the emergence of others. Dermatomyositis has been rarely described in patients with HIV. We present a case of dermatomyositis in a patient with HIV and explore the pathogenesis of autoimmune disorders in HIV focusing on dermatomyositis.

Ollier disease with anaplastic astrocytoma: A review of the literature and a unique case.

BACKGROUND: Ollier disease is a rare, nonfamilial disorder that primary affects the long bones and cartilage of joints with multiple enchondromas. It is associated with a higher risk of central nervous system (CNS) malignancies; although the incidence is unknown. CASE DESCRIPTION: Here, we present the case of a 55-year-old woman who developed an anaplastic astrocytoma with a known diagnosis of Ollier disease with a survival time of over 3 years. CONCLUSION: This report draws attention to the rarity of this disease and the paucity of information regarding CNS involvement in Ollier disease, as well as reviews the current literature.

Prenatally Diagnosed Aggressive Intracranial Immature Teratoma-Clinicopathological Correlation.

OBJECTIVE: To describe clinicopathological correlation of congenital intracranial immature teratoma. METHODS: A retrospective case analysis from a tertiary medical center. RESULTS: We report a case of an intracranial immature teratoma detected prenatally at 35 weeks of gestation. The tumor showed rapid growth, causing acute hydrocephalus requiring subsequent ventriculoperitoneal shunting. Resective surgery was performed within 2 weeks after birth. The infant died at day of life 29. Histological examination revealed an immature teratoma, with high MIB1/Ki-67 proliferation index. CONCLUSION/IMPLICATIONS: Intracranial immature teratoma with high MIB1/Ki-67 proliferation index may serve as an independent poor prognostic factor.

Etanercept-induced myositis: do we have to stop it? A surprising outcome.

We discuss a case of a 47-year-old man who presented with progressive proximal muscle weakness of the upper and lower extremities and unstable gait. He had been on etanercept for 6 months for severe psoriasis and psoriatic arthritis with good control of his disease. Serum creatine kinase (CK) level was found to be 5666 U/L and muscle biopsy showed a marked inflammatory myopathic process likely secondary to etanercept. He was started on high-dose steroids and advised to discontinue etanercept. Despite our recommendation, he never stopped using etanercept due to fear of a psoriasis flare. Three months later, he had significant improvement of clinical symptoms, normalised serum CK levels and discontinued prednisone.

ILAE type 3 hippocampal sclerosis in patients with anti-GAD-related epilepsy.

OBJECTIVE: To describe the neuropathologic findings and clinical course of 2 patients who underwent temporal lobectomy for medically refractive epilepsy and were later found to have high anti-glutamic acid decarboxylase (GAD) concentrations. METHODS: Small case series. RESULTS: Neuropathologic examination of both patients revealed International League Against Epilepsy (ILAE) type 3 hippocampal sclerosis. Following surgery, both developed signs and symptoms of stiff person syndrome and later cerebellar ataxia. Laboratory studies demonstrated high concentrations of anti-GAD antibodies in both patients. CONCLUSIONS: These cases suggest that ILAE type 3 hippocampal sclerosis may be immunologically related to and may exist as part of a broader anti-GAD-related neurologic syndrome in some instances.

TNF-like weak inducer of apoptosis promotes blood brain barrier disruption and increases neuronal cell death in MRL/lpr mice.

Neuropsychiatric disease is one of the most common manifestations of human systemic lupus erythematosus, but the mechanisms remain poorly understood. In human brain microvascular endothelial cells in vitro, TNF-like weak inducer of apoptosis (TWEAK) decreases tight junction ZO-1 expression and increases the permeability of monolayer cell cultures. Furthermore, knockout (KO) of the TWEAK receptor, Fn14, in the MRL/lpr lupus mouse strain markedly attenuates neuropsychiatric disease, as demonstrated by significant reductions in depressive-like behavior and improved cognitive function. The purpose of the present study was to determine the mechanisms by which TWEAK signaling is instrumental in the pathogenesis of neuropsychiatric lupus (NPSLE). Evaluating brain sections of MRL/lpr Fn14WT and Fn14KO mice, we found that Fn14KO mice displayed significantly decreased cellular infiltrates in the choroid plexus. To evaluate the integrity of the blood brain barrier (BBB) in MRL/lpr mice, Western blot for fibronectin, qPCR for iNOS, and immunohistochemical staining for VCAM-1/ICAM-1 were performed. We found preserved BBB permeability in MRL/lpr Fn14KO mice, attributable to reduced brain expression of VCAM-1/ICAM-1 and iNOS. Additionally, administration of Fc-TWEAK intravenously directly increased the leakage of a tracer (dextran-FITC) into brain tissue. Furthermore, MRL/lpr Fn14KO mice displayed reduced antibody (IgG) and complement (C3, C6, and C4a) deposition in the brain. Finally, we found that MRL/lpr Fn14KO mice manifested reduced neuron degeneration and hippocampal gliosis. Our studies indicate that TWEAK/Fn14 interactions play an important role in the pathogenesis of NPSLE by increasing the accumulation of inflammatory cells in the choroid plexus, disrupting BBB integrity, and increasing neuronal damage, suggesting a novel target for therapy in this disease.

Optimizing the skeletal muscle biopsy.

Knowledge of disorders of skeletal muscle remains of importance for the practicing pathologist. While genetic testing has proved useful in the diagnosis of many patients, especially those with the more common forms of muscular dystrophy, less common genetic myopathies, congenital myopathies, and toxic myopathies, often related to commonly used therapeutic agents such as statins, still require pathological analysis for diagnostic purposes. A contemporary pathologist may expect to be consulted about unusual familial neuromuscular disorders, autoimmune disorders, and drug-induced myopathies, often in the context of patients with multiple medical conditions that complicate the clinical and pathological analysis. A working knowledge of skeletal muscle biopsy and its clinical utility as well as its limitations is therefore important for all pathologists. Each pathologist must decide if they wish to process the biopsy in their own laboratory, or if the specimen should be sent to a reference laboratory for analysis.

Brief report: life history and neuropathology of a gifted man with Asperger syndrome.

Despite recent interest in the pathogenesis of the autism spectrum disorders (pervasive developmental disorders), neuropathological descriptions of brains of individuals with well documented clinical information and without potentially confounding symptomatology are exceptionally rare. Asperger syndrome differs from classic autism by lack of cognitive impairment or delay in expressive language acquisition. We examined the 1,570 g brain of a 63 year old otherwise healthy mathematician with an Autistic Spectrum Disorder of Asperger subtype. Except for an atypical gyral pattern and megalencephaly, we detected no specific neuropathologic abnormality. Taken together, the behavioral data and pathological findings in this case are compatible with an early neurodevelopmental process affecting multiple neuroanatomic networks, but without a convincing morphologic signature detectable with routine neuropathologic technology.

Dynamic perfusion MRI characteristics of dural metastases and meningiomas: a pilot study characterizing the first-pass wash-in phase beyond relative cerebral blood volume.

OBJECTIVE: Dural metastases and meningiomas are extraaxial lesions that may be difficult to distinguish using conventional imaging methods. This distinction, however, is clinically important. Perfusion MRI may play a role in preoperative assessment. The aim of this study was to evaluate the utility of perfusion parameters in differentiating between these two entities. In particular, we evaluated two new metrics that reflect the first-pass wash-in characteristics of perfusion. MATERIALS AND METHODS: Patients with intracranial extraaxial masses who underwent perfusion MRI were included. Region-of-interest analysis was performed and several perfusion metrics were calculated including relative cerebral blood volume (rCBV), mean transit time and time to peak (TTP) enhancement from initial bolus enhancement (T0), calculated as TTP-T(0). Two new metrics characterizing first pass wash-in enhancement were also measured: relative wash-in time and wash-in slope. Lesions were divided into two groups: meningioma and metastasis. Comparisons between the two groups were made using Wilcoxon rank sum and Fisher exact tests. RESULTS: Twenty lesions were studied (12 meningioma and 8 metastases). Compared with meningiomas, relative wash-in time was statistically lower in metastases (p < 0.05). No other statistically significant differences were observed. Specifically, there was no difference between the two study groups in rCBV. CONCLUSION: First-pass wash-in characteristics of dural lesions may be useful for evaluating and characterizing lesions. In particular, a metric describing the wash-in phase of perfusion-that is, relative wash-in time-was found to be lower in metastases compared with meningiomas. Contrary to a prior report, we found rCBV to be limited in the evaluation of extraaxial lesions.

Neuropathology of Cockayne syndrome: Evidence for impaired development, premature aging, and neurodegeneration.

Global growth and development failure, premature, accelerated, pathologic aging, and neurodegeneration characterize Cockayne syndrome (CS) and the cerebro-oculo-facial-skeletal and xeroderma pigmentosum/CS syndromes which overlap CS partially in their genetic, somatic, and neuropathologic features. Mutations of CSA or CSB genes jeopardize transcription-coupled repair of damaged nuclear and mitochondrial DNA and resumption of replication and transcription. Resultant defective proteins or gene silencing eventuate in profound dwarfism and micrencephaly, cachexia, vasculopathy, and neurodegeneration. Cellular effects are highly selective. Purkinje cells may die by apoptosis and have grossly dystrophic dendrites. Neuronal death and axonal spheroids indexing neuronal pathology predominate in, but are not limited to, the cerebellum. Progressive loss of retinal, cochlear, and vestibular sensory receptors foster degeneration of ganglion cells and transneuronal brain degeneration. Some proliferating astrocytes are multinucleated and bizarre. Primary damage of oligodendrocytes and Schwann cells may - or may not - explain severe patchy myelin loss ("tigroid leukodystrophy") and segmental demyelinating peripheral neuropathy. Age-related changes are minor in the brain, although precocious severe athero- and arteriolosclerosis are responsible for occasional strokes. Vasculopathology may contribute to myelin loss and to dystrophic mineralization of neurons and vessels, especially in basal ganglia and cerebellum. Understanding the genetics, biochemical, and cellular pathophysiology of these disorders remains fragmentary.

Extensive apoptosis in a case of intractable infantile status epilepticus.

A previously healthy 8 1/2-month-old girl underwent epilepsy surgery for intractable focal seizures with secondary generalization that progressed to status epilepticus. The major neuropathologic finding was extensive apoptosis. Investigations did not reveal any etiology for the apoptosis or the seizures. This is the first report of apoptosis, without necrosis, in association with intractable status epilepticus in the developing human brain. The findings suggest that new treatment strategies targeted to prevent apoptosis may be useful in children with prolonged status epilepticus.