Gene transfer offers the potential to explore basic physiological processes and to intervene in human disease. The central nervous system (CNS) presents a fertile field in which to develop novel therapeutic modalities to treat intractable and pervasive malignant tumors and neurodegenerative disease. The extension of gene therapy to the CNS, however, faces the delivery obstacles of a target population that is postmitotic and isolated behind a blood-brain barrier (BBB). Approaches to this problem have included grafting of genetically modified cells to deliver novel proteins or introducing genes by viral or synthetic vectors geared toward the CNS cell population. Direct inoculation and bulk flow, as well as osmotic and pharmacological disruption, have been used to circumvent the BBB's exclusionary role. Once the gene is delivered, myriad strategies have been used to affect a therapeutic result. Genes activating prodrugs are the most common antitumor approach. Other approaches focus on activating immune responses, targeting angiogenesis, and influencing apoptosis and tumor suppression. At this time, therapy directed at neurodegenerative diseases has centered on ex vivo gene therapy for supply of trophic factors to promote neuronal survival, axonal outgrowth, and target tissue function. Despite early promise, gene therapy for CNS disorders will require advancements in methods for delivery and long-term expression before becoming feasible for human disease.
Gordon Tang and E. Antonio Chiocca
M. Maher Hulou and E. Antonio Chiocca
Atom Sarkar and E. Antonio Chiocca
Neurosurgical “pearls” and neurosurgical evidence
E. Antonio Chiocca
Daniel Ikeda and E. Antonio Chiocca
Andrew Shaw and E. Antonio Chiocca
Daniel Ikeda and E. Antonio Chiocca
Ammar Shaikhouni and E. Antonio Chiocca
Promod Pillai, Abhik Ray-Chaudhury, Mario Ammirati and E. Antonio Chiocca
✓ Sarcoidosis is a multisystemic granulomatous disease characterized by noncaseating epithelioid granulomata that affects the lung in over 90% of patients and the central nervous system (CNS) in 5–9%. Neurosarcoidosis often occurs as multifocal meningeal and parenchymal lesions, and its diagnosis is particularly difficult in the absence of concomitant systemic disease. Hypothalamic-pituitary sarcoidosis occurs in fewer than 10% of patients with neurosarcoidosis and has been previously reported in association with profound endocrinological dysfunction. The authors report the case of a patient with isolated pituitary sarcoidosis who was first evaluated for visual symptoms and showed no preoperative endocrinological dysfunction or evidence of multisystemic or other CNS involvement. To the authors' knowledge, only 1 other such presentation is previously reported in the English literature. Such presentations are diagnostically and therapeutically challenging, and definitive diagnosis requires obtaining a biopsy specimen of the lesion with histological proof of noncaseating epithelioid granuloma, as well as the exclusion of other possible entities.
Kelly Ishizuka, Anne Louise Oaklander and E. Antonio Chiocca
The authors investigated the causes for surgical reexploration in patients with complex regional pain syndrome Type II who received initial relief of pain from implantation of a peripheral nerve stimulator (PNS).
The authors reviewed the charts of 11 consecutive patients who underwent a total of 27 PNS-related operations at one institution. Duration of follow up ranged from 5 days to more than 24 months. Of 11 patients who received PNS implants, seven (64%) required one or more additional surgeries to relocate the PNS because initial pain relief following stimulation was lost and not restored by changing pulse generator settings. Loss of analgesia was attributed to migration of the sutured electrode strip paddle (nine [33%] of 27 surgeries), infection (four [15%] of 27), and the need for placement in an alternative location (three [11%] of 27).
Although infection is attributable to surgical technique, most complications requiring repeated surgery (nine [33%] of 27) are caused by equipment design. Changes in PNS design or in implantation technique might substantially reduce the need for reoperation after PNS implantation.