Long-Term Treatment of Niemann-Pick Type C1 Disease With Intrathecal 2-Hydroxypropyl-ß-Cyclodextrin.

BACKGROUND: Intrathecal 2-hydoxypropyl-ß-cyclodextrin has been found to mobilize cholesterol, extend life, reduce cerebellar pathology, and delay onset of ataxia in the mouse and cat models of Niemann-Pick disease, type C1, a clinically variable progressive and ultimately fatal neurodegenerative storage disorder characterized by endolysosomal accumulation of unesterified cholesterol. OBJECTIVE: In this study, the long-term effects of intrathecal 2-hydoxypropyl-ß-cyclodextrin treatment for 2.5 to three years in humans with Niemann-Pick disease, type C, were evaluated. METHODS: Three patients with Niemann-Pick disease, type C, in different stages of progression and displaying varying disease manifestations were treated with intrathecal 2-hydoxypropyl-ß-cyclodextrin (VTS-270) delivered by lumbar puncture infusion through an intermediate-size patient population investigational new drug application for expanded access. Disease progression was monitored with the Niemann-Pick disease, type C, Neurological Severity Scale and numerous objective measures of function in five neurological domains typically impacted by the disease: cognitive/language, gait/balance, fine motor, swallowing, and eye movement. RESULTS: No worsening in any domain except eye movements (vertical pursuit gain) was seen for any of the three patients, and in the other domains, improved scores on measures were seen over time for one or more patients. The Niemann-Pick disease type C (NPC) Neurological Severity Scale (NSS) showed stable to slightly improved ratings. CONCLUSIONS: These trajectories are not consistent with the typical trajectory of the disease and suggest that intrathecal 2-hydoxypropyl-ß-cyclodextrin has stabilized the disease over an extended period of time, supporting the current phase 2/3 controlled registration trial with VTS-270.

A Case of Bilateral Atrophy of the Inferior Vestibular Nerves.

: We report a case of a 62-year-old woman who was found to have bilateral atrophy of the inferior vestibular nerves on magnetic resonance imaging (MRI) after presenting to our clinic with 6 years of intermittent vertigo and residual unsteadiness. The nerve atrophy may be associated with an episode of vestibular neuritis, a common cause of vertigo that exclusively involves the inferior vestibular nerve in less than 3% of cases. While MRI may demonstrate vestibular nerve enhancement in cases of acute vestibular neuritis, no single MRI finding has been demonstrated consistently among cases of acute or chronic vestibular neuritis. Physical therapy is likely an effective long-term treatment for this patient to achieve central compensation for symptomatic relief.

Fabrication of customized tongue-displacing stents: considerations for use in patients receiving head and neck radiotherapy.

BACKGROUND: Conformal or intensity-modulated radiation therapy can be improved by using a customized tongue-displacing (CTD) stent. These stents are designed to either move healthy oral tissues out of the path of the radiation beam or stabilize mobile tissues to allow more precise field control. METHODS: The authors describe CTD stent construction for both tongue-deviating and tongue-depressing applications. RESULTS: CTD stents enable clinicians to achieve more predictable and consistent radiation dosimetry planning while sparing greater volumes of healthy tissue from damage. They have been well tolerated by patients. CONCLUSIONS: Use of CTD stents results in increased oral mucosal sparing, ensures reproducible immobilization and is incorporated readily into the clinical practice of radiation oncology. Practical Implications. Clinicians can reduce or avoid significant morbidity to healthy oral tissues by using CTD stents. This can lead to better outcomes and improved quality of life for patients receiving head and neck radiation therapy.