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.

We report a case of transthyretin amyloidosis (ATTR) in a 66-year-old man. Genetic testing revealed an exceedingly rare mutation TTR Ala120Ser (c.418G>T, p.Ala140Ser). Only two prior cases with this mutation have been reported. A 66-year-old man of African-Caribbean descent presented with gradually worsening stabbing pain and numbness in bilateral hands and feet over the course of 3 years. These sensory symptoms were most prominent in his fingertips and toes. He also reported a sense of disequilibrium while walking, alternating diarrhea and constipation, and erectile dysfunction. Severe intermittent muscle pains and stiffness were also reported. Bilateral thumb abduction weakness was noted on initial exam. Over time, his proximal muscle strength deteriorated significantly, necessitating the use of assistive devices for ambulation. Intermittent pedal edema was noted; his exercise-tolerance decreased to one block. His past medical history included multiple nerve entrapments, for which he underwent bilateral median nerve and right ulnar nerve release; spinal stenosis with successful laminectomy, seropositive rheumatoid arthritis (RA), gout and overlap syndrome with centromere pattern ANA suggestive of limited scleroderma with Raynaud’s phenomenon. Unintentional weight loss of 90 pounds was noted over the next 2 years; it was attributed to leflunomide that he was taking for RA. His nerve conduction study revealed severe lengthdependent sensorimotor polyneuropathy. Laboratory tests revealed elevated creatine kinase (1100 units-per-liter). Electromyography performed at the time of initial presentation revealed multiple nerve entrapments, sensorimotor axonal polyneuropathy and irritative myopathy. Two years after initial presentation, the patient’s family members mentioned that his younger brother was newly diagnosed with amyloidosis. Our patient underwent deltoid muscle biopsy, which showed amyloid deposition in portions of endomysium (Figure 1). Mass spectroscopy analysis of this sample demonstrated ATTR amyloidosis. Abdominal fat pad biopsy was positive for amyloid using Congo red staining. Amyloidosis secondary to a haematologic issue was unlikely as bone marrow biopsy revealed no evidence of plasma cell dyscrasias or lymphoma. He eventually underwent genetic testing which revealed heterozygous mutation of transthyretin TTR: c.418G>T [p.Ala140Ser (standard nomenclature), also called Ala120Ser (mature protein nomenclature)]. A 2D-transthoracic echocardiogram revealed severe concentric hypertrophy of both ventricles. A 12-lead electrocardiogram revealed sinus-rhythm, low-voltage QRS complexes, q waves in V2/V3 suggestive of pseudo-infarction pattern with poor R-wave progression. A Tc-99m pyrophosphate study noted significant tracer uptake throughout the myocardium with a heart to contralateral ratio (H/CL ratio) of 1.6, also suggestive of transthyretin cardiac amyloidosis. The patient was started on diflusinal and doxycycline but despite that his neuropathy and quality of life continued to worsen. He was deemed to be a poor candidate for liver transplantation given his age and poor performance status. Five years after initial presentation, our patient died from respiratory failure secondary to pneumonia. In terms of family history, the patient’s younger brother was diagnosed with cardiac and gastrointestinal tract amyloidosis at age 64, based on Congo red staining performed on specimen obtained from recto-sigmoid colon. He passed within months of being diagnosed with the disease; he was never genotyped. The patient’s paternal first cousin in Barbados has presented with neuropathy, difficulty ambulating and weight loss in his 60s. The patient’s daughter aged 35 is suffering from neuropathy, carpal tunnel syndrome and weight loss. The patient has four other children, one of whom died of unclear aetiology at age 21; other surviving children are healthy to date. None of the family members have undergone genetic testing to date. The first reported case of this mutation was of a 62-yearold Afro-Caribbean male whose predominant symptoms were cardiomyopathy and peripheral neuropathy [1]. Eleven years later, Luigetti et al. [2] reported the second case in a 64-year-old Italian female who presented with neuropathy, dysautonomia manifesting as gastrointestinal symptoms and weight loss. To our knowledge, this is the first documented case of clinical and histologically confirmed myopathy in a patient with ATTRAla120Ser amyloidosis. Clinically significant myopathy associated with ATTR amyloidosis has rarely been reported in the literature. The signs and symptoms are generally non-specific and are similar to other forms of acquired myopathy. The differential-diagnoses for myopathy in a rheumatologic patient are vast but the presence of neuropathy, cardiomyopathy, and positive family history should facilitate earlier diagnosis and prompt treatment. In addition, this case also broadens our understanding of the possible phenotypic presentations of a very rare genotype of TTR-amyloidosis.

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.

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.

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.

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.

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.

Copyright © 2016 Address correspondenc M.D., M.S., 3400 Bainbr Bronx, NY, 10467; E-ma The author discloses n DOI: 10.1097/MAO.0 According to the World Health Organization, an intraneural perineurioma is a benign tumor of neoplastic perineurial cells (1). Intraneural perineuriomas are slowly progressive, painless lesions commonly found in adolescents and young adults. They predominantly affect motor nerves that lead to progressive loss of motor function, with sensory deficits extremely uncommon (1). Typically indolent in nature, an average duration of symptoms before diagnosis is 53 months (1). Electron microscopy remains the gold standard for diagnosis— demonstrating thin, elongated cytoplasmic processes, poorly formed tight junctions, an incomplete basal lamina, and pinocytic vesicles—while histopathologically they stain positive for epithelial membrane antigen and negative for S-100 protein (1,2). It is generally recommended that the lesion be excised, followed by nerve grafting, to maintain some degree of motor function of the affected nerve. Herein, we describe the case of an intratemporal intraneural perineurioma affecting the seventh cranial nerve, remarking on the clinical and histological findings associated with these lesions.

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 35weeks of gestation. The tumor showed rapid growth, causing acute hydrocephalus requiring subsequent ventriculoperitoneal shunting. Resective surgery was performed within 2weeks 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.

OBJECTIVE : To describe a case of Primary Pineal Malignant Melanoma associated with loss of BAP1.

Objective: To describe two cases of a supratentorial variant of CLIPPERS we propose to call SLIPPERS Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder characterized by a combination of clinical symptoms correlating to magnetic resonance gadolinium enhancing lesions of the pons. Rare cases of CLIPPERS with additional supratentorial or spinal lesions have been reported. These inflammatory enhancements improve with steroid therapy, which manifest clinically, but return once steroids are discontinued. We have seen two patients with a similar condition confined to supratentorial locations, analogous to CLIPPERS, which we propose to call SLIPPERS. Methods/Design: The patients were seen at a tertiary medical center. We present two patients followed > 4 years. Patient A initially presented with recurrent seizure episodes; patient B with headache and hemiparesis. Results: In both cases, initial MRI revealed enhancing supratentorial lesions corresponding to initial clinical presentations. Initial work-up revealed negative serum and CSF testing for inflammatory and autoimmune markers as well as infectious etiologies. Both patients underwent brain biopsy: Patient A’s biopsy revealed perivascular inflammation consisting of CD4/CD8 T lymphocytes. Patient B’s biopsy revealed infiltrative CD3 T lymphocytes. Both patients were started on steroid therapy with partial clinical and radiologic response, but repeated recurrence upon tapering steroid therapy. Steroid sparing immunosuppressive therapy seemed effective for chronic suppression of inflammation. Conclusion: We have seen two cases of an entity that is clinically, radiologically and pathologically similar to CLIPPERS, but isolated to the supratentorial compartment, which we propose to call SLIPPERS. Disclosure: Dr. Armand has nothing to disclose. Dr. Graber has received personal compensation for activities with Stemedica Inc., Novocure Inc., and Biogen Idec. Dr. Lado has nothing to disclose. Dr. LaSala has nothing to disclose. Dr. Weidenheim has nothing to disclose.

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.

OBJECTIVE: To report a case of orgasmic auras as an initial symptom of a primary brain tumor and review the literature on orgasmic auras. BACKGROUND: Orgasmic auras and ictal events are rare. A limited number of case reports and reviews have been published since the early 1980’s. These cases offer valuable information in regards to sexual function localization in the human brain. DESIGN/METHODS: Medical record review and literature search using PubMed. RESULTS: A 56 year old presented to the emergency room for confusion. He had become disoriented while watching television. Although the patient denied previous symptoms, he described sensations of unprovoked sexual arousal and orgasm occurring a few times daily and lasting several seconds in the few years preceding. His initial neurological exam, including a detailed mental status exam, was normal. Laboratory work up was unremarkable. MRI scan of the brain with gadolinium contrast revealed an infiltrative non-enhancing 3x4 cm lesion in the right medial temporal lobe. Levetiracetam was introduced at a dose of 500 mg twice daily under suspicion of partial seizures with and without dyscognitive features. Open biopsy revealed WHO Grade 2 oligodendroglioma. At follow up the patient complained of continued unprovoked orgasmic sensations. Levetiracetam dosing was escalated with cessation of these sensations. Several months later the patient complained of recurrence. Repeat MRI studies showed new tumor growth. Temozolamide was initiated with post chemotherapy radiation planned. Lacosamide was added as second line anti-seizure therapy. CONCLUSIONS: In the large majority of published cases of orgasmic auras, including this case, events can be localized to the right temporal lobe. Orgasmic auras appear to have powerful localizing value and once established can aid in long term management decisions, particularly in the case of primary brain tumors. Study Supported by: None Disclosure: Dr. Glover has nothing to disclose. Dr. LaSala has nothing to disclose. Dr. Weidenheim has nothing to disclose. Dr. Graber has received personal compensation for activities with Stemedica Inc., Novocure Inc., and Biogen Idec.

OBJECTIVE: To describe a case of JC Virus spectrum disease in an immunocompromised patient with relapsing course and neuronal involvement. BACKGROUND: PML associated with JCV is a common cause of neurologic deterioration among HIV patients. JCV in HIV patients can have atypical imaging appearance including post-gadolinium enhancement. While PML has long been associated with intranuclear inclusions of JCV in glial cells, recently a novel phenotype has been found associated with productive neuronal infection, JCV Granule Cell Neuronopathy. Repeated survival and recurrence, as seen in our case, is very unusual. DESIGN/METHODS: Case Study RESULTS: A 47 year-old woman with HIV infection on HAART (CD4 count 154, nadir 19, VL 57) and previous PML diagnosis with residual L hemiparesis was referred to our hospital for eye pain and visual field defect. Examination showed a R homonymous hemianopia and L arm and leg contracture with weakness beyond baseline. MRI of brain showed a new 8mm cortically-based enhancing focus in the L occipital lobe. Lumbar puncture demonstrated 2 WBCs, normal protein and glucose, and negative bacterial and viral cultures. CSF cytology was negative for atypical or malignant cells. Due to concern of primary CNS lymphoma, brain biopsy was performed. Pathology showed perivascular inflammatory cell infiltrate. Stains were negative for bacteria, fungi, AFB, toxoplasma, CMV, HSV, and HPV. A papovavirus (SV40) stain was strongly positive consistent with PML. Intraneuronal inclusions consistent with JCV were found. The patient was continued on HAART and mirtazapine was started. CONCLUSIONS: This case highlights the significant workup that can be needed to confirm a diagnosis of PML in HIV patients. While cerebellar granule cell infection is an increasingly recognized variant of JCV associated disease, there have been few reports of intraneuronal JCV infection in the cortex. This case helps broaden the spectrum of disease associated with JCV in immunocompromised patients. Disclosure: Dr. Gutman has nothing to disclose. Dr. Weidenheim has nothing to disclose. Dr. LaSala has nothing to disclose. Dr. Graber has received personal compensation for activities with Stemedica Inc., Novocure Inc., and Biogen Idec.

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.

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.