Anti-Abeta antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice.

Neuritic plaques are a defining feature of Alzheimer disease (AD) pathology. These structures are composed of extracellular accumulations of amyloid-beta peptide (Abeta) and other plaque-associated proteins, surrounded by large, swollen axons and dendrites (dystrophic neurites) and activated glia. Dystrophic neurites are thought to disrupt neuronal function, but whether this damage is static, dynamic, or reversible is unknown. To address this, we monitored neuritic plaques in the brains of living PDAPP;Thy-1:YFP transgenic mice, a model that develops AD-like pathology and also stably expresses yellow fluorescent protein (YFP) in a subset of neurons in the brain. Using multiphoton microscopy, we observed and monitored amyloid through cranial windows in PDAPP;Thy-1:YFP double-transgenic mice using the in vivo amyloid-imaging fluorophore methoxy-X04, and individual YFP-labeled dystrophic neurites by their inherent fluorescence. In vivo studies using this system suggest that amyloid-associated dystrophic neurites are relatively stable structures in PDAPP;Thy-1:YFP transgenic mice over several days. However, a significant reduction in the number and size of dystrophic neurites was seen 3 days after Abeta deposits were cleared by anti-Abeta antibody treatment. This analysis suggests that ongoing axonal and dendritic damage is secondary to Abeta and is, in part, rapidly reversible.

Deep brain stimulation of a patient with psychogenic movement disorder.

BACKGROUND: The long-term safety of deep brain stimulation (DBS) is an important issue because new applications are being investigated for a variety of disorders. Studying instances where DBS was inadvertently implanted in patients without a movement disorder may provide information about the safety of the therapy. We report the case of a patient with a psychogenic movement disorder treated with deep brain stimulation (DBS). CASE DESCRIPTION: The patient presented at our clinic after 5 years of chronic DBS of the subthalamic nucleus (STN) for presumed Parkinson's disease. A dopamine transporter (DAT) scan (DaTscan) showed normal DAT distribution in the striatum. A positron emission tomography (PET) scan showed no abnormal metabolic patterns. Further psychiatric and neurological evaluations revealed that the patient was suffering from a psychogenic movement disorder. The patient displayed no sign or symptom from the stimulation, and DBS did not lead to any benefits or side effects for this patient. CONCLUSION: We argue that the absence of side effects, the normal DaTscan, and PET scan after 5 years of chronic stimulation illustrate the safety of DBS on neural tissue.

A paradigm for the evaluation and management of spinal coccidioidomycosis.

BACKGROUND: Coccidioidomycosis is a fungal infection that is endemic to parts of the Southwestern United States. When infection involves the spine, the treatment strategies can be challenging. We have devised a management protocol for spinal coccidioidomycosis based on a review of the literature and our experience. METHODS: The electronic literature search of National Library of Medicine for publications from 1964 to 2014 was performed using the following keywords: Coccidioidomycosis and spine. The search yielded 24 papers. Treatment strategies were summarized into a treatment protocol. RESULTS: A total of 164 cases of spinal coccidioidomycosis were identified, ranging in age from <10 to >80 years. Males (n = 131) and African-Americans (n = 79) were strikingly over-represented. Medical therapy: Once a diagnosis of spinal coccidioidomycosis is established, antifungal therapy should always be started. Antifungal therapy with amphotericin B or azoles like fluconazole. Medical therapy needs to be continued for many years and sometimes indefinitely to reduce disease recurrence or progression. Surgical management is indicated in cases with mechanical instability, neurologic deficit, medically intractable pain, or progression of infection despite antifungal therapy. CONCLUSIONS: This work provides a working protocol involving assessment and reassessment for the management of spinal coccidioidomycosis. Medical management with antifungal agents in some cases can provide satisfactory disease control. However, in patients with mechanical instability, neurologic deficit, medically intractable pain or disease progression disease control may only be achieved with surgical debridement and stabilization.

Use of a stop-flow programmable shunt valve to maximize CNS chemotherapy delivery in a pediatric patient with acute lymphoblastic leukemia.

BACKGROUND: The requirement for frequent intraventricular drug delivery in the setting of shunt dependence is particularly challenging in the treatment of central nervous system infection, neoplastic disease, and hemorrhage. This is especially relevant in the pediatric population where both hematogenous malignancy requiring intrathecal drug delivery and shunt-dependent hydrocephalus are more prevalent. Intrathecal and intraventricular chemotherapy agents can be prematurely diverted in these shunt-dependent patients. CASE DESCRIPTION: We report the use of a stop-flow programmable shunt valve to maximize delivery of intraventricular chemotherapy in a child with acute lymphoblastic leukemia and disseminated intravascular coagulation who presented with spontaneous intracerebral and intraventricular hemorrhages. The patient then developed posthemorrhagic hydrocephalus and eventually progressed to shunt dependence but still required frequent intraventricular chemotherapy administration. A ventriculoperitoneal shunt, equipped with a valve that allows for near cessation of cerebrospinal fluid flow (Certas(®), Codman, Raynham, MA), and a contralateral Ommaya reservoir were inserted to maximize intraventricular dissemination of chemotherapy. CONCLUSIONS: To the best of our knowledge, this is the first reported case of the use of a high-resistance programmable valve being used to virtually cease cerebrospinal fluid flow through the distal catheter temporarily in order to maximize intraventricular drug dissemination in a pediatric patient with acute lymphoblastic leukemia.