Progressive multifocal leukoencephalopathy without overt immunosuppression.

Progressive multifocal leukoencephalopathy (PML) is a central nervous system disease caused by the human polyomavirus 2 that usually occurs in a setting of immunodeficiency. PML without overt immunosuppression is considered a rare occurrence but has been described in multiple previous case reports and series. Its prevalence, overall frequency, and prognosis are largely unknown. This is a single-center retrospective review of all University of Florida cases with the ICD10 PML diagnosis code (A81.2). PML without overt immunosuppression was defined as absence of human immunodeficiency virus (HIV) infection, hematological malignancy, immunomodulatory/-suppressive medications, autoimmune conditions with a propensity for PML (sarcoidosis, systemic lupus erythematosus). Cases that did not fulfill criteria for clinically or histologically definite PML were excluded. Of 52 patients with the ICD10 code A 81.2, 17 fulfilled definite diagnostic criteria for PML. Overt immunosuppression was identified in 15/17 (88.2%) cases (10/17 (58.8%): human immunodeficiency virus; 5/17 (29.4%): immunomodulatory/-suppressive medication). Two/seventeen (11.8%) cases were consistent with PML without overt immunosuppression. Possible contributing factors were a preceding dog bite and mild hypogammaglobulinemia M (39 mg/dL) in case 1 and significant alcohol use without evidence for liver disease in case 2. Both cases were fatal within 6 (case 1) and 2 (case 2) months. The results suggest that PML without overt immunosuppression may be more common than previously described. Therefore, PML should be considered even in the absence of overt immunosuppression if clinical and radiographic findings are suggestive of the diagnosis.

Recurrent diabetic myonecrosis in an African American woman with long-standing uncontrolled type 2 diabetes: a case report.

BACKGROUND: Diabetic myonecrosis, also called diabetic muscle infarction, is an uncommon complication of uncontrolled diabetes mellitus and is frequently underdiagnosed. The objective of this case report is to highlight the challenges in the early diagnosis and treatment of this disease. CASE PRESENTATION: A 51-year-old African American woman with a long history of uncontrolled diabetes mellitus presented to her primary care physician with right thigh pain. A diagnosis of diabetes myonecrosis was made on the basis of magnetic resonance imaging, biopsy, and negative autoimmune panel. After failing conservative treatment, the patient was treated with prednisone with gradual improvement of her symptoms. However, she had a recurrence of myonecrosis almost one year after her original presentation, which was also treated with prednisone. The recurrence had a shorter course and the patient recovered well. Challenges to the treatment in this patient were her debilitating pain and her underlying chronic kidney disease. CONCLUSIONS: A high index of suspicion for diabetic myonecrosis is necessary when a patient with diabetes presents with unilateral focal leg pain and swelling. Magnetic resonance imaging and biopsy can help confirm the diagnosis. Prednisone may be considered in patients who lack spontaneous regression with just rest. Educating healthcare professionals about this uncommon condition is of utmost importance in avoiding unnecessary testing and inappropriate treatment.

Clival Paraganglioma, Case Report and Literature Review.

Paragangliomas are rare tumors that may present with cranial neuropathies when located along the skull base. Supratentorial paragangliomas are less likely to secrete catecholamines but should be worked up, nonetheless. We highlight a case of a female in her fourth decade found to have a petroclival lesion following initial presentation that included one month of tooth pain, dysphagia, diplopia, hoarseness and right hemifacial hypoesthesia. Magnetic resonance imaging of the brain demonstrated a T2 hyperintense lesion favored to be a petroclival meningioma. Pre-operative angiography demonstrated a hypervascular tumor. She underwent a combined presigmoid craniotomy with posterior petrosectomy performed by both neurosurgery and neuro-otology. Pathology demonstrated paraganglioma. She had small volume residual tumor and is planned for continued outpatient radiotherapy. Paragangliomas should be on the differential for skull base lesions. Management paradigm involves multidisciplinary care and a combination of surgical resection and post-operative radiation. In this paper, we discuss underlying pathophysiology as well as appropriate workup and management.

A 60-Year-Old Man With Dyspnea, Proximal Muscle Weakness, and Pulmonary Arterial Hypertension.

CASE PRESENTATION: A 60-year-old man with no significant medical history presented to the pulmonology clinic with 2 years of progressive weakness and shortness of breath. Showering and other activities of daily living caused him significant fatigue and dyspnea. He had a 20-pack-year smoking history, but no significant history of alcohol or illicit drug use. He did not take any prescribed or over-the-counter medications for chronic medical conditions and had never been on statin therapy. Vital signs were significant for an oxygen saturation of 91% on 4-L nasal cannula. He required up to 6 L of oxygen during a walk test. Physical examination showed mild inspiratory crackles in the lung bases, loud splitting of the second pulmonic valve (P2) with a right parasternal heave, and 2+ pitting edema in the lower extremities. There was muscle weakness, pain, and wasting of the proximal upper and lower extremities, particularly in his legs. He denied any joint pain, and there was no evidence of rash or dysphagia.

Suboccipital Craniotomy and C1 Laminectomy for Atypical Choroid Plexus Papilloma.

Atypical choroid plexus papilloma is a rare pediatric brain tumor that has distinct clinical and pathologic features. In this case, we highlight the diagnosis and management of this rare disease. The details of case positioning and execution are discussed. The case review is utilized as an overview of histopathologic findings, to discuss clinical features of the disease, and to highlight areas warranting further investigation. In particular, we provide insight into the typical clinical course post-treatment.

Fidelity of muscle fibre reinnervation modulates ageing muscle impact in elderly women.

KEY POINTS: Susceptibility to age-related muscle atrophy relates to the degree of muscle denervation and the capacity of successful reinnervation. However, the specific role of denervation as a determinant of the severity of muscle aging between populations with low versus high physical function has not been addressed. We show that prefrail/frail elderly women exhibited marked features of muscle denervation, whereas world class octogenarian female master athletes showed attenuated indices of denervation and greater reinnervation capacity. These findings suggest that the difference in age-related muscle impact between low- and high-functioning elderly women is the robustness of the response to denervation of myofibers. ABSTRACT: Ageing muscle degeneration is a key contributor to physical frailty; however, the factors responsible for exacerbated vs. muted ageing muscle impact are largely unknown. Based upon evidence that susceptibility to neurogenic impact is an important determinant of the severity of ageing muscle degeneration, we aimed to determine the presence and extent of denervation in pre-frail/frail elderly (FE, 77.9 ± 6.2 years) women compared to young physically inactive (YI, 24.0 ± 3.5 years) females, and contrast these findings to high-functioning world class octogenarian female masters athletes (MA, 80.9 ± 6.6 years). Muscle biopsies from vastus lateralis muscle were obtained from all three groups to assess denervation-related morphological and transcriptional markers. The FE group displayed marked grouping of slow fibres, accumulation of very small myofibres, a severe reduction in type IIa/I size ratio, highly variable inter-subject accumulation of neural cell adhesion molecule (NCAM)-positive myofibres, and an accumulation of pyknotic nuclei, indicative of recurring cycles of denervation/reinnervation and persistent denervation. The MA group exhibited a smaller decline in type IIa/I size ratio and fewer pyknotic nuclei, accompanied by a higher degree of type I fibre grouping and larger fibre group size, suggesting a greater reinnervation of denervated fibres. Consistent with this interpretation, MA had higher mRNA levels of the reinnervation-promoting cytokine fibroblast growth factor binding protein 1 (FGFBP1) than FE. Our results indicate that the muscle of FE women has significant neurogenic atrophy, whereas MA muscle exhibit superior reinnervation capacity, suggesting that the difference in age-related muscle impact between low- and high-functioning elderly women is the robustness of the response to denervation of myofibres.

Brainstem angiocentric glioma: report of 2 cases.

Angiocentric glioma is a rare tumor that was recognized by the WHO Classification of Tumours of the Central Nervous System as a distinct clinicopathological entity in 2007. Since this initial description, the vast majority of cases of angiocentric glioma reported in the literature have involved tumors of the cerebral hemispheres. To date, only 1 case of angiocentric glioma arising from the posterior midbrain has been reported. The authors present the cases of 2 pediatric patients who were found to have brainstem angiocentric gliomas. The clinical course, radiological and pathological features, treatment, and follow-up are described. The first case is one of a 5-year-old girl who presented with double vision, headache, and nausea and was found to have a midbrain lesion with pathological features consistent with angiocentric glioma. She was treated with resection and endoscopic third ventriculostomy (ETV), followed by close observation and serial neuroimaging. The second case is one of a 6-year-old boy who presented with progressive mouth drooping and problems with balance. He was found to have a pontine lesion with pathological features consistent with angiocentric glioma. This patient was treated with ETV, followed by close observation and serial neuroimaging. This report includes 6 and 1.5 years of follow-up of the patients, respectively. While there are limited data regarding the prognosis or long-term management of patients with brainstem angiocentric gliomas, the cases described in this report suggest an indolent course for this tumor, similar to the course of angiocentric gliomas located in the cerebral hemispheres.

A Case Presentation: Rare Occurrence of an Adolescent Male Presenting With an ATRT and Simultaneous Low-grade Glioneuronal Tumor.

Atypical rhabdoid/teratoid tumor (ATRT) is an uncommon and highly malignant tumor of the central nervous system. The majority of ATRT tumors occur in infancy and young children located in the posterior fossa. The ideal treatment for cure remains controversial and prognosis is typically unfavorable. We present a case of an atypical presentation of ATRT, presenting in adolescence with an additional low-grade glioneuronal tumor discovered at diagnosis.

The burden and risk factors of ventriculostomy occlusion in a high-volume cerebrovascular practice: results of an ongoing prospective database.

OBJECT Ventriculostomy occlusion is a known complication after external ventricular drain (EVD) placement. There have been no prospective published series that primarily evaluate the incidence of and risk factors for EVD occlusion. These phenomena are investigated using a prospective database. METHODS An ongoing prospective study of all patients undergoing frontal EVD placement in the Neurosurgery Intensive Care Unit at the University of Florida was accessed for the purposes of this analysis. Demographic, procedural, and radiographic data were recorded prospectively and retrospectively. The need for catheter irrigation or replacement was meticulously documented. Univariate and multivariate regression analyses were performed. RESULTS Ninety-eight of 101 total enrolled patients had accessible data, amounting to 131 total catheters and 1076 total catheter days. Nineteen percent of patients required at least 1 replacement. Forty-one percent of catheters developed at least 1 temporary occlusion, with an average of 2.4 irrigations per patient. Intracranial hemorrhage occurred in 28% of patients after the first EVD placement (2% resulting in new neurological deficit) and in 62% of patients after 1 replacement. The cost of occlusion is estimated at $615 per enrolled patient. Therapeutic anticoagulation and use of small EVD catheters were statistically significant predictors of permanent occlusion (p = 0.01 and 0.04, respectively). CONCLUSIONS EVD occlusion is frequent and imparts a significant burden in terms of patient morbidity, physician upkeep, and cost. This study suggests that developing strategies or devices to prevent EVD occlusion, such as the preferential use of larger diameter catheters, may be beneficial in reducing the burden associated with ventriculostomy malfunction.

CNS intraoperative consultation: a survival guide for non-neuropathologists.

Intraoperative consultations for central nervous system disease may be challenging due to limitations of sample size, lack of familiarity with neurosurgical procedures, or poor access to neuroimaging studies. Despite these challenges, the surgical pathologist is charged with determining if the tissue sample is representative of the pathologic process while ensuring that enough diagnostic tissue has been retained for routine histology, immunohistochemistry, fluorescence in situ hybridization, molecular testing, and in some cases, tissue banking. Here, we present basic methods and a practical approach for CNS intraoperative consultation including critical pre-analytic considerations that promote optimal tissue management.

Gliosis versus glioma?: don't grade until you know.

A major challenge in the routine practice of surgical neuropathology is the distinction between reactive astrocytosis, which may be because of non-neoplastic and neoplastic conditions, and a low-grade infiltrating diffuse astrocytoma [World Health Organization (WHO) grade II]. This can be particularly challenging with small biopsies that often yield limited amounts of tissue for pathologic study, especially considering the marked differences in prognosis and therapy after a pathologic diagnosis. This paper will review some basic principles of gliosis as an astrocytic reaction to a wide range of central nervous system insults and focus on some common diagnostic pitfalls such as (1) gliosis associated with brain tumor mimics, including demyelinating disease and infections, (2) gliosis associated with nonglial tumors such as craniopharyngioma, hemangioblastoma, metastases, and central nervous system lymphoma. New diagnostic methods have facilitated the differentiation between reactive astrocytosis and the diffuse gliomas. Of these, the use of mutated isocitrate dehydrogenase-1 (IDH-1) as a marker of diffuse infiltrating astroctomas, oligodendrogliomas, and a subset of glioblastomas (secondary glioblastomas) is particularly exciting for tissue diagnosis and patient prognosis. In addition IDH-1 may be useful to distinguish a diffuse infiltrating glioma from low-grade "focal" neoplasms such as the pilocytic astocytoma in histologically ambiguous cases. The discovery of BRAF mutations as molecular signatures of some pilocytic astrocytomas, gangliogliomas, and pleomorphic xanthoastrocytomas has provided another diagnostic tool for the pathologist. Only after a definitive diagnosis of a diffuse infiltrating glioma or a focal glioma is made should a tumor grade be applied and some practical issues in current glioma grading are provided.

Pilomyxoid astrocytoma in unusual location in a child with neurofibromatosis type 1: case report and review of the literature.

Pilomyxoid astrocytoma (PMA) is a recently defined brain tumor believed to be a variant of pilocytic astrocytoma (PA), but with a more aggressive course. Most PMAs occur in the optic-chiasmatic/hypothalamic (OCH) region but they have also been described in the posterior fossa, temporal lobe, and in the spinal cord. We report a girl with history of neurofibromatosis type 1 (NF-1) who presented with a PMA located in the left lateral ventricle. Despite the fact that most of PMAs occur in the hypothalamic region, high awareness should be given to lesions in unusual locations, thus expanding the current epidemiologically known locations for this tumor.