Metastatic Pleomorphic Lobular Carcinoma of the Breast to the Hypothalamus Presenting as a Primary Pituitary Lesion Presenting 17 Years Later-Report of a Case and Review of the Literature.

Carcinomas metastatic to the brain are common, however, metastatic disease to the hypothalamic- pituitary region is uncommon and account for less than 3.6% of all resected malignant pituitary tumors. Most metastatic disease in that region derives from a lung or breast primary, with both ductal and lobular carcinoma reported. We report what we believe is the first case of pleomorphic lobular carcinoma metastatic to the hypothalamus. This case is also reaffirms that late metastasis from breast cancer should be considered in the differential diagnosis. It is important for the clinician to consider the clinical history of breast cancer, even when remote, in the differential diagnosis.

Chondromyxoid Fibroma of the Sacral Spine.

Background and Importance. Chondromyxoid fibromas are rare tumors of cartilaginous origin typically found in long bones. They usually present during the second and third decades of life. In this case report, we describe the case of a 60-year-old male who presented with back pain and was later found to have a sacral mass. Further immunohistochemical analysis determined that the mass was a chondromyxoid fibroma. Clinical Presentation. A 60-year-old male presented with worsening lower back pain over the course of 2 years. Magnetic resonance imaging demonstrated a destructive mass centered at S4 with heterogeneous enhancement. The patient underwent an S3-to-Co1 laminectomy for gross total resection of the tumor. Histology demonstrated a biphasic, lobulated appearance, characteristic of a chondromyxoid fibroma. The tissue stained faintly positive for multicytokeratin, and it was negative for markers S-100 protein and brachyury, indicating that it was not a chordoma. Conclusion. Only 8 cases have documented sacral chondromyxoid fibroma. As these are exceedingly rare tumors, especially within the sacral spine, the differential diagnosis includes other malignant tumors more likely to be found in the spine, particularly chordomas and chondrosarcomas. Immunohistochemistry and histology are essential in making a definitive diagnosis. This case provides a comprehensive illustration of the clinical presentation, radiographic findings, and immunohistochemistry of sacral chondromyxoid fibroma.

Epidermoid Cyst of the Lumbar Spine After Lumbar Puncture: A Clinical, Radiographic, and Pathologic Correlation.

BACKGROUND: Epidermoid cysts can rarely arise as a late complication of lumbar puncture. We describe a young man who had a remote history of a lumbar puncture and who was subsequently found to have a lumbar spinal epidermoid cyst on imaging, after presenting with lower extremity radicular pain. CASE DESCRIPTION: A 24-year-old man with a remote history of lumbar puncture presented with lower back pain and radicular leg pain which had been ongoing for over a year. Despite conservative management, the patient's symptoms progressed to worsening back pain and left L4 radiculopathy. Magnetic resonance imaging of the lumbar spine demonstrated a peripherally enhancing, intradural, extramedullary lesion at L4-5. Diffusion-weighted imaging revealed diffusion restriction within the lesion, characteristic of an epidermoid cyst. The patient underwent an L4-5 laminectomy for resection of the intradural tumor. The lesion was noted to contain pearly white granules consistent with the appearance of an epidermoid cyst. Histopathology confirmed the diagnosis. On follow-up examination, the patient demonstrated improvement of his back pain and resolution of radicular symptoms. CONCLUSIONS: Lumbar spinal epidermoid cysts may be either congenital or secondary to an iatrogenic cause. This patient had a remote history of lumbar puncture during workup for meningitis as a child. As a complication of a lumbar puncture, the formation of an epidermoid cyst can occur and is thought to be the result of implanted cutaneous tissue. This case provides a comprehensive illustration of the clinical, radiographic, intraoperative, and pathologic findings consistent with an iatrogenic epidermoid cyst.

Efficient Expression of HIV in Immunocompetent Mouse Brain Reveals a Novel Nonneurotoxic Viral Function in Hippocampal Synaptodendritic Injury and Memory Impairment.

HIV causes neurodegeneration and dementia in AIDS patients, but its function in milder cognitive impairments in virologically suppressed patients on antiretroviral therapy is unknown. Such patients are immunocompetent, have low peripheral and brain HIV burdens, and show minimal brain neuropathology. Using the model of HIV-related memory impairment in EcoHIV-infected conventional mice, we investigated the neurobiological and cognitive consequences of efficient EcoHIV expression in the mouse brain after intracerebral infection. HIV integrated and persisted in an expressed state in brain tissue, was detectable in brain monocytic cells, and caused neuroinflammatory responses and lasting spatial, working, and associative memory impairment. Systemic antiretroviral treatment prevented direct brain infection and memory dysfunction indicating the requirement for HIV expression in the brain for disease. Similarly inoculated murine leukemia virus used as a control replicated in mouse brain but not in monocytic cells and was cognitively benign, linking the disease to HIV-specific functions. Memory impairment correlated in real time with hippocampal dysfunction shown by defective long-term potentiation in hippocampal slices ex vivo and with diffuse synaptodendritic injury in the hippocampus reflected in significant reduction in microtubule-associated protein 2 and synapsin II staining. In contrast, there was no evidence of overt neuronal loss in this region as determined by neuron-specific nuclear protein quantification, TUNEL assay, and histological observations. Our results reveal a novel capacity of HIV to induce neuronal dysfunction and memory impairment independent of neurotoxicity, distinct from the neurotoxicity of HIV infection in dementia.IMPORTANCE HIV neuropathogenesis has been attributed in large measure to neurotoxicity of viral proteins and inflammatory factors produced by infected monocytic cells in the brain. We show here that HIV expression in mouse brain causes lasting memory impairment by a mechanism involving injury to hippocampal synaptodendritic arbors and neuronal function but not overt neuronal loss in the region. Our results mirror the observation of minimal neurodegeneration in cognitively impaired HIV patients on antiretroviral therapy and demonstrate that HIV is nonneurotoxic in certain brain abnormalities that it causes. If neurons comprising the cognition-related networks survive HIV insult, at least for some time, there is a window of opportunity for disease treatment.

Adult Diagnosis of Type 1 Fiber Predominance Myopathy Caused by Novel Mutations in the RYR1 Gene.

We describe a 57-year-old patient with mild diffuse weakness that was incidentally detected when he was evaluated for restless leg syndrome. An electromyography confirmed the presence of a myopathy without suggestion of inflammatory myopathy. A muscle biopsy demonstrated type 1 fiber predominance with minimal inflammatory features suggesting a genetic myopathy. Exome sequencing revealed c.10648C > T variant (p.R3550W), and a novel variant, c.10749_10753delGGAGG (E3584Rfs*3), in the ryanodine receptor 1 (RYR1) gene transmitted through his asymptomatic father indicating these mutations are in trans. Prompted by these results, a 47-year-old sister presented for evaluation. Her examination showed mild proximal muscle weakness, and an electromyography confirmed a noninflammatory myopathy. Her genotype was identical to her affected brother confirming that in these siblings, the RYR1 mutations, transmitted in an autosomal recessive pattern, are the cause of their myopathy. The adult age at diagnosis of these affected siblings likely reflects the mild and minimally progressive nature of the myopathy.

Spinal racemose cysticercosis: case report and review.

Cysticercosis is a common helminthic infection worldwide, endemic in Central and South America, sub-Saharan Africa, and Southeast Asia. Neurocysticercosis typically involves brain parenchyma, subarachnoid space, and the ventricular system. Although the spinal cord is frequently involved in patients with parenchymal neurocysticercosis, isolated spinal involvement is rare, occurring in only 1-3% of patients. We report a case of racemose spinal neurocysticercosis with brain parenchyma involvement in a 49-year-old Mexican man, who presented with unsteady gait and bilateral arm numbness and weakness. Magnetic resonance imaging revealed multiseptated cystic lesions in the upper cervical spinal canal and nonenhancing intradural extramedullary cystic lesions in the thoracic spine. The patient underwent sub-occipital craniectomy with decompression, followed by a course of steroids and albendazole. Pathology confirmed the diagnosis of neurocysticercosis, and the patient's symptoms resolved after treatment. We include discussion on the symptoms, diagnosis, and treatment of neurocysticercosis with a focus on the spinal form.

Minimally manipulative extraction of polycystic cervical neurocysticercosis.

CLINICAL HISTORY: Intradural, extramedullary cervical spinal involvement is an uncommon manifestation of neurocysticercosis. CASE REPORT: A case of a middle-aged man with neurocysticercosis in the intradural extramedullary cervical spine and brain who originally presented with bilateral paresthesias of his extremities, with a progressively unsteady gait. Magnetic resonance imaging revealed cystic enhancing lesions in the brain and cervical region of the spine, with the largest cyst extending from the posterior fossa through C2, causing spinal cord compression. The patient underwent surgical resection of the intradural extramedullary cervical spinal lesions, and he has continued to improve clinically, with no recurrence of cystic lesions. CONCLUSION: When examining patients with clinical signs of a spinal mass lesion, the differential diagnosis should include neurocysticercosis of the spine.

Intraventricular granulomatous mass associated with Mycobacterium haemophilum: A rare central nervous system manifestation in a patient with human immunodeficiency virus infection.

We report a rare case of Mycobacterium haemophilum presenting as an intraventricular granulomatous mass with loculated hydrocephalus and seizures in a patient with human immunodeficiency virus. M. haemophilum, a slow-growing mycobacteria, causes localized and disseminated disease among immunocompromised hosts. Central nervous system infection with M. haemophilum is extremely rare. Preoperative laboratory testing of our patient for tuberculosis, toxoplasmosis, sarcoidosis and histoplasmosis were negative. Surgical resection of the mass revealed a caseating granuloma that stained positive for acid-fast bacillus suggesting possible tuberculoma. Despite negative testing for tuberculosis, a polymerase chain reaction analysis was ultimately performed from the resected mass which revealed M. haemophilum. To our knowledge, this is the first case of M. haemophilum presenting as an intraventricular mass. We review the clinical manifestations of this pathogen and discuss the medical and surgical management.

Enhanced human immunodeficiency virus Type 1 expression and neuropathogenesis in knockout mice lacking Type I interferon responses.

The roles of Type I interferon (IFN) in human immunodeficiency virus Type 1 (HIV-1) neuropathogenesis are poorly understood; both protective and deleterious effects of IFN signaling have been described. We used genetically modified mice deficient in the Type I IFN receptor (IFNRKO) to analyze the progress of HIV-1 brain infection and neuropathogenesis in the absence of IFN signaling. IFNRKO and wild-type (WT) mice on the 129xSv/Ev or C57BL/6 strain backgrounds were infected systemically with EcoHIV, a chimeric HIV-1 that productively infects mice. IFNRKO mice showed higher HIV-1 expression in spleen and peritoneal macrophages and greater virus infiltration into the brain compared to WT mice. Neuropathogenesis was studied by histopathological, immunohistochemical, immunofluorescence, and polymerase chain reaction analyses of brain tissues after the virus was inoculated into the brain by stereotaxic intracerebral injection. Both IFNRKO and WT mice showed readily detectable HIV-1 and brain lesions, including microglial activation, astrocytosis, and increased expression of genes coding for inflammatory cytokines and chemokines typical of human HIV-1 brain disease. Parameters of HIV-1 neuropathogenesis, including HIV-1 expression in microglia/macrophages, were significantly greater in IFNRKO than in WT mice. Our results show unequivocally that Type I IFN signaling and responses limit HIV-1 infection and pathogenesis in the brains of mice.

Presentation of cauda equina syndrome due to an intradural extramedullary abscess: a case report.

BACKGROUND CONTEXT: Cauda equina syndrome is caused by compression or injury to the nerve roots distal to the level of the spinal cord. This syndrome presents as low back pain, motor and sensory deficits in the lower extremities, and bladder as well as bowel dysfunction. Although various etiologies of cauda equina syndrome have been reported, a less common cause is infection. PURPOSE: To report a case of cauda equina syndrome caused by infection of an intradural extramedullary abscess with Staphylococcus aureus. STUDY DESIGN/SETTING: Case report and review of the literature. METHODS: The literature regarding the infectious causes of cauda equina syndrome was reviewed and a case of cauda equina syndrome caused by infection of an intradural extramedullary abscess with Staphylococcus aureus was reported. RESULTS: A 37-year-old woman, with history of intravenous drug abuse, hepatitis C, and hepatitis B, presented with low back pain lasting 2 months, lower extremity pain, left greater than right with increasing weakness and difficulty ambulating, and urinary and fecal incontinence. Her presentation was consistent with cauda equina syndrome. The patient underwent a T12-L2 laminectomy, and intradural exploration revealed an abscess. Methicillin-resistant Staphylococcus aureus was found on wound culture. CONCLUSIONS: Cauda equina syndrome, presenting as a result of spinal infection, such as the case reported here, is extremely rare but clinically important. Surgical intervention is generally the recommended therapeutic modality.

Inclusion-body myositis associated with Alzheimer's disease.

Sporadic inclusion-body myositis (s-IBM) is a myopathy that is characterized by progressive weakness and muscle pathology demonstrating inflammation and rimmed vacuoles. In addition, similar to the pathology observed in the brains of patients with Alzheimer's disease, the deposition of beta-amyloid and phosphorylated tau proteins in muscle fibers has been reported. These shared pathologic features have prompted hypotheses suggesting a shared etiology of these two conditions. We report a case of a 73-year-old woman initially diagnosed with s-IBM who later developed Alzheimer's disease.

Mice chronically infected with chimeric HIV resist peripheral and brain superinfection: a model of protective immunity to HIV.

Infection by some viruses induces immunity to reinfection, providing a means to identify protective epitopes. To investigate resistance to reinfection in an animal model of HIV disease and its control, we employed infection of mice with chimeric HIV, EcoHIV. When immunocompetent mice were infected by intraperitoneal (IP) injection of EcoHIV, they resisted subsequent secondary infection by IP injection, consistent with a systemic antiviral immune response. To investigate the potential role of these responses in restricting neurotropic HIV infection, we established a protocol for efficient EcoHIV expression in the brain following intracranial (IC) inoculation of virus. When mice were inoculated by IP injection and secondarily by IC injection, they also controlled EcoHIV replication in the brain. To investigate their role in EcoHIV antiviral responses, CD8+ T lymphocytes were isolated from spleens of EcoHIV infected and uninfected mice and adoptively transferred to isogenic recipients. Recipients of EcoHIV primed CD8+ cells resisted subsequent EcoHIV infection compared to recipients of cells from uninfected donors. CD8+ spleen cells from EcoHIV-infected mice also mounted modest but significant interferon-γ responses to two HIV Gag peptide pools. These findings suggest EcoHIV-infected mice may serve as a useful system to investigate the induction of anti-HIV protective immunity for eventual translation to human beings.

Vascular inflammation with eosinophils after the use of n-butyl cyanoacrylate liquid embolic system.

OBJECTIVE AND IMPORTANCE: Currently, n-butyl cyanoacrylate (n-BCA) is one of the most widely used liquid embolic agents in the treatment of intracranial arteriovenous malformations (AVMs). The cases of three patients are reported who underwent endovascular embolization with n-BCA, followed by resection in two and post-embolization hemorrhage with emergent evacuation in one, with histologic demonstration of an eosinophilic vasculitis found in resected AVM specimens. This is probably the first report of this tissue reaction, which may have theoretically serious clinical implications. CLINICAL PRESENTATION: In this series, three patients (2 women, 1 man) presented with intracranial AVMs (Spetzler-Martin I-III) with the lesions located in the frontal lobe in two of the patients and in the parietal lobe in one. All patients presented with headache, and one also had new-onset seizures. INTERVENTION: All patients underwent embolization with n-BCA before a planned, staged surgical resection of the embolized AVMs. One patient had four embolizations over a 5-month period, one had three embolizations over 3 months complicated by hemorrhage after embolization requiring emergent evacuation of the hematoma, and the third patient had a single embolization. In all three patients, surgical and autopsy specimens showed an inflammatory response within the embolized vasculature with a prominent eosinophilic infiltrate. CONCLUSION: The eosinophilic vasculitis seen in the pathology specimens may represent a previously undocumented hypersensitivity reaction following exposure to n-BCA, with the potential for adverse sequelae, including increased risk of hemorrhage as was seen in one of our patients.

A second case of Marburg's variant of multiple sclerosis with vasculitis and extensive demyelination.

Marburg's variant of multiple sclerosis is a rapidly progressive and malignant form of multiple sclerosis (MS) that usually leads to severe disability or death within weeks to months without remission. Few cases have been described in the literature since the original description by Marburg. The classic pathological findings usually include highly destructive zones of extensive demyelination, necrosis with dense cellular infiltrate, and giant reactive astrocytes. We report a case of a 31-year-old woman with Marburg's variant of MS who, over a period of eight months, became totally disabled, blind, and quadriplegic, with vocal cord paralysis, requiring a tracheostomy. The patient underwent diagnostic stereotactic brain biopsy. Clinical findings, magnetic resonance imaging (MRI), serologic and cerebrospinal fluid (CSF) findings, and neuropathology are discussed. MRI showed extensive white matter involvement in the brain and spinal cord that continuously progressed over time. A diagnostic stereotactic brain biopsy revealed extensive active demyelination with unexpected finding of active vasculitis and fibrinoid necrosis with a vascular inflammatory cell infiltrate, including polymorphonuclear neutrophils and rare eosinophils. Serologic work-up for vasculitis and neuromyelitis optica was unremarkable and the CSF showed only one oligoclonal band (OCB) not present in serum. This is the second case of Marburg's variant of MS that demonstrated both demyelination and vasculitis. In our case these features were demonstrated simultaneously, even though the demyelination was the predominant pathological finding. Since vasculitis is not a feature of classic MS, these findings pose the question as to whether Marburg's variant of MS is a true variant or different entity altogether.

I-Z-I complexes in congenital myopathy.

A 3-month-old boy with hypotonia at birth succumbed to a congenital myopathy. The major finding in his muscle biopsy corresponded to I-Z-I complexes described previously in embryonic skeletal muscle. A few previous myopathy cases have described findings suggestive of I-Z-I-like complexes. A mutation affecting mononuclear myoblasts or early myotubes was suspected, although an acquired lesion could not be ruled out. The findings may also have been altered by secondary events in this unusual case.

Regression of multiple intracranial meningiomas after cessation of long-term progesterone agonist therapy.

The authors present the case of a patient that demonstrates the long-standing use of megestrol acetate, a progesterone agonist, and its association with multiple intracranial meningioma presentation. Discontinuation of megestrol acetate led to shrinkage of multiple tumors and to the complete resolution of one tumor. Histological examination demonstrated that the largest tumor had high (by > 25% of tumor cell nuclei) progesterone-positive expression, including progesterone receptor (PR) isoform B, compared with low expression of PR isoform A; there was no evidence of estrogen receptor expression and only unaccentuated collagen expression. This is the first clinical report illustrating a causal relationship between exogenous hormones and modulation of meningioma biology in situ.

Paraneoplastic SIADH and Dermatomyositis in Cervical Cancer: A Case Report and Literature Review.

We present the first known case of a patient with cervical squamous cell carcinoma complicated by paraneoplastic syndromes of both dermatomyositis and inappropriate secretion of antidiuretic hormone (SIADH). The patient in this case presented with generalized body pain and vaginal bleeding. Her cervical cancer was diagnosed as stage IIB by physical exam, imaging, and cervical biopsy, her dermatomyositis was confirmed by muscle and skin biopsy, and her SIADH was diagnosed based on laboratory findings.