Robert J. Stokroos

Van Buchem disease (hyperostosis corticalis generalisata) maps to chromosome 17q12-q21

Van Buchem disease (hyperostosis corticalis generalisata; OMIM 239100 [http://www3.ncbi.nlm.nih. gov:80/htbin-post/Omim/dispmim?239100]) is an autosomal recessive disorder characterized by hyperostosis of the skull, mandible, clavicles, ribs, and diaphyseal cortices of the long bones. The most striking clinical features are the enlargement of the jaw and the thickness of the skull, which may lead to facial nerve palsy, hearing loss, and optic atrophy. Increased formation, by osteoblasts, of qualitatively normal bone has been proposed as the underlying pathological mechanism, but the molecular defect is unknown. We studied 11 van Buchem patients and their highly inbred family, who live in The Netherlands in a small ethnic isolate, that had a common ancestor approximately 9 generations ago. A genomewide search with highly polymorphic microsatellite markers showed linkage to marker D17S1299 on chromosome 17q12-21 (maximum LOD score of 8.82 at a recombination fraction [straight theta] of .01). Analysis of additional markers from that region delineated a candidate region of <1 cM, between markers D17S1787 and D17S934. Interestingly, the only marker not showing recombination with the disease locus was an intragenic marker of the thyroid-hormone receptor alpha1 (THRA1) gene, which generated a LOD score of 12.84 at straight theta=.00. Since thyroid hormones are known to stimulate bone resorption, the THRA1 gene might be involved in the etiology and pathogenesis of van Buchem disease. Unraveling the underlying mechanism for this disorder could contribute to the understanding of the regulatory processes conditioning bone density and the underlying pathological processes.

Reanimation of the paralyzed face by indirect hypoglossal-facial nerve anastomosis.

Abstract Background: The results of indirect hypoglossal facial nerve anastomosis with interposition of a free nerve graft, end-to-end to the periferal facial nerve stump, and end-to-side to the hypoglossal nerve are prospectively evaluated. This technique is supposed to overcome loss of hypoglossal function. Methods: Tongue function in 39 consecutive patients and facial reanimation in 29 patients who completed 24 months follow-up were assessed. Facial nerve function was judged using the House-Brackmann (HB) grading system. Results: Tongue movements were normal in all operated on patients. Initial facial movements occurred on average 7.5 months postoperatively. The results were graded HB II in 6 (20.9%), HB III in 13 (44.6%), HB IV in 7 (24.1%), HB V in 2 (6.8%) patients, and HB VI in 1 (3.4%) patient. The results were significantly better in young patients and when a short time interval between paralysis and surgery existed. Conclusions: Indirect hypoglossal-facial anastomosis is the preferred technique in most patients for whom the classical direct hypoglossofacial anastomosis is indicated.

Management of large vestibular schwannoma. Part I. Planned subtotal resection followed by Gamma Knife surgery: radiological and clinical aspects

OBJECT In large vestibular schwannoma (VS), microsurgery is the main treatment option, and complete resection is considered the primary goal. However, previous studies have documented suboptimal facial nerve outcomes in patients who undergo complete resection of large VSs. Subtotal resection is likely to reduce the risk of facial nerve injury but increases the risk of lesion regrowth. Gamma Knife surgery (GKS) can be performed to achieve long-term growth control of residual VS after incomplete resection. In this study the authors report on the results in patients treated using planned subtotal resection followed by GKS with special attention to volumetric growth, control rate, and symptoms. METHODS Fifty consecutive patients who underwent the combined treatment strategy of subtotal microsurgical removal and GKS for large VSs between 2002 and 2009 were retrospectively analyzed. Patients with neurofibromatosis Type 2 were excluded. Patient charts were reviewed for clinical symptoms. Audiograms were evaluated to classify hearing pre- and postoperatively. Preoperative and follow-up contrast-enhanced T1-weighted MR images were analyzed using volume-measuring software. RESULTS Surgery was performed via a translabyrinthine (25 patients) or retrosigmoid (25 patients) approach. The median follow-up was 33.8 months. Clinical control was achieved in 92% of the cases and radiological control in 90%. One year after radiosurgery, facial nerve function was good (House-Brackmann Grade I or II) in 94% of the patients. One of the two patients who underwent surgery to preserve hearing maintained serviceable hearing after resection followed by GKS. CONCLUSIONS Considering the good tumor growth control and facial nerve function preservation as well as the possibility of preserving serviceable hearing and the low number of complications, subtotal resection followed by GKS can be the treatment option of choice for large VSs.

Review: cochlear implants as a treatment of tinnitus in single-sided deafness

Purpose of reviewTinnitus is a symptom that is highly associated with hearing loss. Its incidence is expected to increase due to the detrimental effects of occupational and leisure noise. Even though no standard treatment is currently available, the effect of cochlear implants on tinnitus in single-sided deafness (SSD) is under scientific attention. This review reveals an overview of all publicly available reports about cochlear implant as a treatment for tinnitus in SSD. Recent findingsCochlear implantation in SSD suppresses tinnitus in most of the cases. Some studies even demonstrate complete tinnitus suppression after implantation. No tinnitus worsening is reported in any of the cases. Furthermore, tinnitus does not restore during the electrical stimulation presented by the cochlear implant. The tinnitus level seems to stabilize after 3–6 months after the first fitting. SummaryAlthough the underlying mechanism responsible for the observed tinnitus suppression is not yet clear, cochlear implantation should be considered as a treatment option for tinnitus arising from SSD. However, appropriate patient selection is essential as it is expected that it is a requirement that tinnitus arises from cochlear deafferentation.

Selective vestibular ablation by intratympanic gentamicin in patients with unilateral active ménière's disease: a prospective, double-blind, placebo-controlled, randomized clinical trial

Objective To establish the efficacy of intratympanic gentamicin treatment in patients with unilateral Ménières disease. Material and Methods This was a prospective, double-blind, randomized clinical trial of intratympanic gentamicin versus intratympanic buffer solution (placebo) in patients with established active Ménières disease in the affected ear. Outcome measures included the number of vertiginous spells, degree of sensorineural hearing loss, labyrinthine function and labyrinthine asymmetry. Results Topical gentamicin provided a significant reduction in the number of vertiginous spells, although a “placebo effect” was also observed. Sensorineural hearing loss did not occur in the gentamicin group, although some deterioration occurred in the placebo group. Conclusions Intratympanic gentamicin is a safe and efficient treatment for the vertiginous spells associated with Ménières disease. When applied early in the course of the disease, it may prevent some of the sensorineural hearing deterioration associated with it.

Habituation to galvanic vestibular stimulation for analysis of postural control abilities in gymnasts.

The possible correlation between postural control abilities in gymnasts and the sensitivity for and the degree of short-term habituation to galvanic vestibular stimulation (GVS) was studied. Seven balance trained young girls (Dutch National Junior Gymnasts Championship) versus seven non-trained girls and twenty-five women underwent computer-controlled GVS using a monaural continuous 1-cosinusoidal stimulus of 0.5 Hz and 2 mA, repeated three times on each side [Balter, Stokroos, Boumans, Kingma, Acta Otolaryngol. (in press); Balter, Stokroos, Eterman, Paredis, Orbons, Kingma, Acta Otolaryngol. (in press)]. Results showed that mean total galvanic-induced body sway (GBS) gain was significantly lower in the trained and untrained girls compared to the adult women (P < 0.05). Mean habituation to GVS (learning abilities), however, showed no significant differences between the three groups. We suggest that the superior balance control in professional gymnasts is primarily achieved through motor training and not by learning abilities or a higher sensitivity of the vestibular system [Neurosci. Lett. 225 (1998) 155].

Artificial balance: restoration of the vestibulo-ocular reflex in humans with a prototype vestibular neuroprosthesis

The vestibular system plays a crucial role in the multisensory control of balance. When vestibular function is lost, essential tasks such as postural control, gaze stabilization, and spatial orientation are limited and the quality of life of patients is significantly impaired. Currently, there is no effective treatment for bilateral vestibular deficits. Research efforts both in animals and humans during the last decade set a solid background to the concept of using electrical stimulation to restore vestibular function. Still, the potential clinical benefit of a vestibular neuroprosthesis has to be demonstrated to pave the way for a translation into clinical trials. An important parameter for the assessment of vestibular function is the vestibulo-ocular reflex (VOR), the primary mechanism responsible for maintaining the perception of a stable visual environment while moving. Here we show that the VOR can be artificially restored in humans using motion-controlled, amplitude modulated electrical stimulation of the ampullary branches of the vestibular nerve. Three patients received a vestibular neuroprosthesis prototype, consisting of a modified cochlear implant providing vestibular electrodes. Significantly higher VOR responses were observed when the prototype was turned ON. Furthermore, VOR responses increased significantly as the intensity of the stimulation increased, reaching on average 79% of those measured in healthy volunteers in the same experimental conditions. These results constitute a fundamental milestone and allow us to envision for the first time clinically useful rehabilitation of patients with bilateral vestibular loss.

The Modified Ampullar Approach for Vestibular Implant Surgery: Feasibility and Its First Application in a Human with a Long-Term Vestibular Loss

Objective: To assess, for the first time in a human with a long-term vestibular loss, a modified approach to the ampullae and the feasibility of evoking a VOR by ampullar stimulation. Materials and methods: Peroperative stimulation of the ampullae, using the ampullar approach, was performed under full anesthesia during cochlear implantation in a 21-year-old female patient, who had experienced bilateral vestibular areflexia and sensorineural hearing loss for almost 20 years. Results: The modified ampullar approach was performed successfully with as minimally invasive surgery as possible. Ampullar stimulation evoked eye movements containing vectors congruent with the stimulated canal. As expected, the preliminary electrophysiological data were influenced by the general anesthesia, which resulted in current spread and reduced maximum amplitudes of eye movement. Nevertheless, they confirm the feasibility of ampullar stimulation. Conclusion: The modified ampullar approach provides safe access to the ampullae using as minimally invasive surgery as possible. For the first time in a human with long-term bilateral vestibular areflexia, it is shown that the VOR can be evoked by ampullar stimulation, even when there has been no vestibular function for almost 20 years. This approach should be considered in vestibular surgery, as it provides safe access to one of the most favorable stimulus locations for development of a vestibular implant.

The Diagnostic Accuracy of Non-Echo-Planar Diffusion-Weighted Imaging in the Detection of Residual and/or Recurrent Cholesteatoma of the Temporal Bone

BACKGROUND AND PURPOSE: Non-EPI DWI is a promising alternative to second-look surgery for the detection of residual and/or recurrent cholesteatoma. We evaluated the diagnostic accuracy, expressed as a positive predictive value, of MR imaging for the detection of residual and/or recurrent cholesteatoma in our hospital. MATERIALS AND METHODS: Fifty-six MR imaging studies were performed from 2005 to 2010 in patients having previously undergone surgery for cholesteatoma. Pre- and postgadolinium T1-weighted, T2-weighted, and non-EPI DWI sequences were performed and correlated with clinical and intraoperative findings. Twenty-seven patients underwent second-look surgery; 7 were under close clinical follow-up. Twenty-two patients without evidence of cholesteatoma were under regular follow-up (range, 14–44 months). RESULTS: Non-EPI DWI sequences showed increased DW signal intensity in 36 patients. Of those, 27 had second-look surgery, confirming cholesteatoma in 25 patients; in 1 patient, an empyema was diagnosed, and in the other patient, no cholesteatoma was found at surgery. In 2 patients who had not undergone surgery, increased DW signal intensity was accompanied by hyperintense signal intensity on T1-weighted images, consistent with transplanted fat in the postoperative cavity. The positive predictive value for detection of cholesteatoma was 93% (25/27). CONCLUSIONS: Residual and/or recurrent cholesteatomas after primary cholesteatoma surgery can be accurately detected by increased DW signal intensity on non-EPI DWI. However, DWI without conventional sequences increased the risk of misdiagnosis in our patient setting because transplanted fat within the postoperative cavity may show increased DW signal intensity.

Therapy of Idiopathic Sudden Sensorineural Hearing Loss: Antiviral Treatment of Experimental Herpes Simplex Virus Infection of the Inner Ear

Experimental herpes simplex virus type 1 (HSV-1) labyrinthitis provides a model of idiopathic sudden sensorineural hearing loss (ISSHL). Corticosteroids improve the prognosis for hearing recovery in ISSHL, but the effects of acyclovir are unknown. To establish the therapeutic efficacy of acyclovir (Zovirax) and prednisolone in experimental HSV-1 viral labyrinthitis, we induced HSV-1 labyrinthitis in 12 guinea pigs. Three animals received no treatment, 3 received prednisolone, 3 received acyclovir, and 3 received both. Four other animals served as controls, receiving culture medium only. Hearing, HSV-1 antibody titers, and cochlear damage were evaluated. The HSV-1 labyrinthitis caused hearing loss within 24 hours. Combination treatment consisting of prednisolone and acyclovir resulted in earlier hearing recovery and less extensive cochlear destruction compared to prednisolone or acyclovir as a monotherapy. The beneficial effect of this treatment modality remains to be demonstrated in ISSHL.