The relaxation response resiliency program (3RP) in patients with neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis: results from a pilot study.

NF1, NF2, and Schwannomatosis are incurable tumor suppressor syndromes associated with poor quality of life. The aim of this study was to determine the feasibility, acceptability, and preliminary efficacy of an NF adapted, 8-week group mind body skills based intervention, the relaxation response resiliency program (3RP) aimed at improving resiliency and increasing satisfaction with life. Patients seen at MGH's Neurofibromatosis Clinic were offered participation if they described difficulties coping to a treating physician. Participants completed measures of life satisfaction, resiliency, stress, mood, lifestyle, pain, post-traumatic growth and mindfulness at baseline and after completing the 3RP program. The intervention had relative feasible enrollment rate (48% rate, 32 out of 67 of patients signing the informed consent form). However, out of the 32 patients who signed the informed consent, only 20 started the study (62.5%) and only 16 completed it (50%), suggesting problems with feasibility. The main reason cited for non-participation was burden of travel to the clinic. The intervention was highly acceptable, as evidenced by an 80% completion rate (16/20). Paired t tests showed significant improvement in resiliency, satisfaction with life, depression, stress, anxiety, mindfulness and post traumatic growth, with effect sizes ranging from 0.73-1.33. There was a trend for significance for improvement in somatization and sleepiness (p = 0.06), with effect sizes of 0.54-0.92 respectively. Statistically nonsignificant improvement was observed in all other measures, with effect sizes small to medium. In sum, the 3RP was found to be relatively feasible, highly acceptable and preliminary efficacious in decreasing symptom burden in this population, supporting the need of a randomized controlled trial.

Bilateral electric stimulation from auditory brainstem implants in a patient with neurofibromatosis type 2.

BACKGROUND: Recent developments in the field of electronic hearing prostheses have allowed for the introduction of auditory brainstem implants in patients with neurofibromatosis type 2. CASE REPORT: Bilateral electric stimulation from 2 sequentially placed auditory brainstem implants was applied in a 27-year-old man with neurofibromatosis type 2. CONCLUSIONS: Results of the present case support further application of bilateral electric stimulation from auditory brainstem implants for patients with neurofibromatosis type 2.

Effects of phase duration and pulse rate on loudness and pitch percepts in the first auditory midbrain implant patients: Comparison to cochlear implant and auditory brainstem implant results.

The auditory midbrain implant (AMI), which is designed for stimulation of the inferior colliculus (IC), is now in clinical trials. The AMI consists of a single shank array (20 contacts) and uses a stimulation strategy originally designed for cochlear implants since it is already approved for human use and we do not yet know how to optimally activate the auditory midbrain. The goal of this study was to investigate the effects of different pulse rates and phase durations on loudness and pitch percepts because these parameters are required to implement the AMI stimulation strategy. Although each patient was implanted into a different region (i.e. lateral lemniscus, central nucleus of IC, dorsal cortex of IC), they generally exhibited similar threshold versus phase duration, threshold versus pulse rate, and pitch versus pulse rate curves. In particular, stimulation with 100 mus/phase, 250 pulse per second (pps) pulse trains achieved an optimal balance among safety, energy, and current threshold requirements while avoiding rate pitch effects. However, we observed large differences across patients in loudness adaptation to continuous pulse stimulation over long time scales. One patient (implanted in dorsal cortex of IC) even experienced complete loudness decay and elevation of thresholds with daily stimulation. Comparing these results with those of cochlear implant and auditory brainstem implant patients, it appears that stimulation of higher order neurons exhibits less and even no loudness summation for higher rate stimuli and greater current leakage for longer phase durations than that of cochlear neurons. The fact that all midbrain regions we stimulated, which includes three distinctly different nuclei, exhibited similar loudness summation effects (i.e. none for pulse rates above 250 pps) suggests a possible shift in some coding properties that is affected more by which stage along the auditory pathway rather than the types of neurons are being stimulated. However, loudness adaptation occurs at multiple stages from the cochlea up to the midbrain.

Rehabilitation of hearing and communication functions in patients with NF2.

Most patients with neurofibromatosis type 2 (NF2) lose hearing either spontaneously or after removal of their neurofibromas. The patient may benefit from conventional hearing aids if, due to modern microsurgery and intraoperative monitoring the integrity of the cochlea and the 8th nerve is preserved. With lost auditory function but preserved electrical stimulibility of the 8th nerve a cochlear implant may be appropriate. But if the patients have no remaining 8th nerve to stimulate, there is no benefit from cochlear implants. Until some years ago, vibrotactile aids, lip-reading, and sign language have been the only communication modes available to these patients. With auditory brain stem implants it is now possible to bypass both the cochlea and the 8th nerve and to stimulate the cochlear nucleus directly. Stimulation of the devices produces useful auditory sensations in almost all patients. Testing of perceptual performance indicated significant benefit from the device for communication purposes, including sound-only sentence recognition scores and the ability to converse on the telephone. Also lip-reading is significantly improved with brain stem implants. The successful work of an auditory brainstem program center depends very much on the close interdisciplinary collaboration between the Departments of Neurosurgery and ENT-surgery. In the future new developments like speech processing strategies and new designed electrodes accessing the complex tonotopic organization of the cochlear nucleus may further improve rehabilitation in these patients who would have been deaf some years ago.

Enhanced proliferation and potassium conductance of Schwann cells isolated from NF2 schwannomas can be reduced by quinidine.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disease that is characterized mainly by schwannomas, as well as menigiomas and gliomas. The NF2 gene product merlin/schwannomin acts as a tumor suppressor. Schwann cells derived from NF2 schwannomas showed an enhanced proliferation rate, and electrophysological studies revealed larger K(+) outward currents as compared with controls. Schwann cells isolated from schwannomas of NF2 patients or multiorgan donors were treated with different concentrations of the K(+) current blockers quinidine, tetraethylammonium chloride, and 4-aminopyridine and K(+) outward currents and proliferation rates of these cells were compared. K(+) outward currents of both cell types can be blocked by quinidine. Importantly, treatment with quinidine reduces proliferation of NF2 Schwann cells in a concentration dependent manner but did not reduce proliferation of normal Schwann cells. Therefore, the use of quinidine or quinidine-like components would possibly provide a novel adjuvant therapeutic option for NF2 patients to slow down or freeze growth of schwannomas.

Evaluation of surgical approaches to endoscopic auditory brainstem implantation.

OBJECTIVES: This study investigates the use of endoscopy for the placement of an auditory brainstem implant by translabyrinthine, retrosigmoid (suboccipital), and middle cranial fossa approaches. STUDY DESIGN: Cadaver dissection and endoscope-assisted placement of the auditory brainstem implant. METHODS: Translabyrinthine, retrosigmoid, and middle cranial fossa dissections were performed bilaterally in five cadaveric heads. An auditory brainstem implant was placed within the lateral recess of the fourth ventricle under endoscopic visualization. The implantation was performed with all approaches and documented by digital image capture followed by production of dye-sublimation photographic prints. RESULTS: The lateral recess was visualized with the endoscope in all three approaches to the brainstem. The 30 degrees endoscope provided the best visualization by translabyrinthine and retrosigmoid dissection and was essential for the middle cranial fossa approach. Refinement of implant position was readily achieved, as even the deepest portion of the recess could be seen with all three approaches. CONCLUSIONS: This study finds that endoscopy provides superior visualization of the lateral recess of the fourth ventricle than the operating microscope with all approaches. The retrosigmoid approach is recommended, as it provides the best view of the implantation site and the easiest angle for placement of the prosthesis. The use of the endoscope may allow for a smaller craniotomy than with conventional microscopic techniques, depending on tumor size. The translabyrinthine approach provides a good view of the lateral recess but had no advantage over other approaches. The middle cranial fossa approach is only possible with angled endoscopes; however, it is technically the most difficult and places the facial nerve at greatest risk.