Surgical decision-making in superior canal dehiscence syndrome with concomitant otosclerosis.

OBJECTIVE: The diagnosis and management of Superior Canal Dehiscence Syndrome (SCDS) with concomitant otosclerosis can be a challenge. Otosclerosis can mask SCDS symptoms and stapes surgery may reveal or exacerbate vestibular symptoms. Our aim is to present four cases of SCDS with concomitant otosclerosis and thereby informing the reader about the possibility of this dual occurrence and its implications for treatment. CASES: Four patients with SCDS and concomitant otosclerosis are presented. Two patients underwent surgical treatment for both SCDS and otosclerosis and two patients opted for conservative management. OUTCOMES: The main differences between surgically and non-surgically treated cases are the presence of autophony and pressure-induced vertigo and a more severe experience of symptoms in surgically treated cases. Surgically treated cases achieved a sizeable reduction in postoperative air-bone gap and resolution of vestibular symptoms. CONCLUSION: The subjective severity of symptoms in combination with shared decision-making is key in determining the appropriate treatment plan for SCDS and concomitant otosclerosis.

Treatment of a floppy epiglottis with upper airway stimulation therapy.

PURPOSE: To evaluate the efficacy of upper airway stimulation therapy in patients with a floppy epiglottis who have experienced continuous positive airway pressure failure or intolerance. METHODS: A retrospective single-center cohort study was conducted. Patients who received an Inspire Upper Airway Stimulation system and had a 1-year follow-up were included. Baseline and one-year in-laboratory polysomnography examinations were performed. Patient characteristics, Epworth Sleepiness Scale scores and upper airway stimulation device settings were collected. RESULTS: A total of 75 patients were included, of whom 10 had a floppy epiglottis. Patients with a floppy epiglottis had a significant therapeutic response to upper airway stimulation therapy, similar to patients without a floppy epiglottis. According to the Sher's success criteria, 90% of patients with a floppy epiglottis and 68% of patients without a floppy epiglottis were responders to therapy (p = 0.149). In the floppy epiglottis group, the apnea-hypopnea index decreased from 35.1 ± 5.5 events/hour to 11.2 ± 11.3 events/hour (95% CI (15.0, 32.9), p < 0.001), similarly in the non-floppy epiglottis group, the decline was from 36.4 ± 8.3 events/hour to 14.4 ± 9.5 events/hour (95% CI (18.6, 25.2), p < 0.001, between groups p = 0.659). Comparable reductions were observed for the other respiratory parameters. CONCLUSION: Treatment of patients with obstructive sleep apnea and a floppy epiglottis can be challenging. Continuous positive airway pressure may aggravate the epiglottis collapse. Upper airway stimulation therapy can be considered an effective alternative treatment option for patients with a floppy epiglottis who have encountered either continuous positive airway pressure failure or intolerance.

Aminoglycoside- and glycopeptide-induced ototoxicity in children: a systematic review.

BACKGROUND: Ototoxicity has been reported after administration of aminoglycosides and glycopeptides. OBJECTIVES: To identify available evidence for the occurrence and determinants of aminoglycoside- and glycopeptide-related ototoxicity in children. MATERIALS AND METHODS: Systematic electronic literature searches that combined ototoxicity (hearing loss, tinnitus and/or vertigo) with intravenous aminoglycoside and/or glycopeptide administration in children were performed in PubMed, EMBASE and Cochrane Library databases. Studies with sample sizes of ≥50 children were included. The QUIPS tool and Cochrane criteria were used to assess the quality and risk of bias of included studies. RESULTS: Twenty-nine aminoglycoside-ototoxicity studies met the selection criteria (including 7 randomized controlled trials). Overall study quality was medium/low. The frequency of hearing loss within these studies ranged from 0%-57%, whereas the frequency of tinnitus and vertigo ranged between 0%-53% and 0%-79%, respectively. Two studies met the criteria on glycopeptide-induced ototoxicity and reported hearing loss frequencies of 54% and 55%. Hearing loss frequencies were higher in gentamicin-treated children compared to those treated with other aminoglycosides. In available studies aminoglycosides had most often been administered concomitantly with platinum agents, diuretics and other co-medication. CONCLUSIONS: In children the reported occurrence of aminoglycoside/glycopeptide ototoxicity highly varies and seems to depend on the diagnosis, aminoglycoside subtype and use of co-administered medication. More research is needed to investigate the prevalence and determinants of aminoglycoside/glycopeptide ototoxicity. Our results indicate that age-dependent audiological examination may be considered for children frequently treated with aminoglycosides/glycopeptides especially if combined with other ototoxic medication.

Differences in characteristics between people with tinnitus that seek help and that do not.

Knowledge on characteristics of people that seek help for tinnitus is scarce. The primary objective of this study was to describe differences in characteristics between people with tinnitus that seek help compared to those who do not seek help. Next, we described differences in characteristics between those with and without tinnitus. In this cross-sectional study, we sent a questionnaire on characteristics in different domains; demographic, tinnitus-specific, general- and psychological health, auditory and noise- and substance behaviour. We assessed if participants had sought help or planned to seek help for tinnitus. Tinnitus distress was defined with the Tinnitus Functional Index. Differences between groups (help seeking: yes/no, tinnitus: yes/no) were described. 932 people took part in our survey. Two hundred and sixteen participants were defined as having tinnitus (23.2%). Seventy-three of those sought or planned to seek help. A constant tinnitus pattern, a varying tinnitus loudness, and hearing loss, were described more frequently in help seekers. Help seekers reported higher TFI scores. Differences between help seekers and people not seeking help were mainly identified in tinnitus- and audiological characteristics. These outcomes might function as a foundation to explore the heterogeneity in tinnitus patients.

Tinnitus treatment by vagus nerve stimulation: A systematic review.

BACKGROUND: Tinnitus is a phantom sensation of sound, which can have a negative impact on quality of life of those affected. No curative treatments are currently known. Neuromodulation by vagus nerve stimulation has emerged as a new treatment option for tinnitus, though till date the effectiveness remains unclear. Therefore, we aim to review the effect of vagus nerve stimulation on tinnitus distress and tinnitus symptom severity in patients with chronic tinnitus. METHODS: We searched Pubmed, Embase and the Cochrane Library systematically for RCTs, observational studies and case studies on the effect of VNS treatment for tinnitus on October 29, 2019. Studies including adult patients with subjective tinnitus, comparing transcutaneous or implantable VNS to placebo or no treatment or before and after application of VNS treatment on tinnitus distress and tinnitus symptom severity measured with a validated questionnaire were eligible. The risk of bias was assessed with the appropriate tool for each type of study. RESULTS: Our search identified 9 primary studies of which 2 RCTs, 5 cohort studies and 2 case series or reports. 5 studies used transcutaneous VNS treatment and 4 used implanted VNS treatment. 6 studies combined VNS treatment with sound therapy. There was a serious risk of bias in all studies, especially on confounding. Most studies reported a small decrease in tinnitus distress or tinnitus symptom severity. CONCLUSION: Due to methodological limitations and low reporting quality of the included studies, the effect of VNS on tinnitus remains unclear. To draw conclusions for which patient population and to what extent (t)VNS is beneficial in the treatment of tinnitus, a randomised controlled trial should be considered.

Clinical Outcomes of Soft Tissue Preservation Surgery With Hydroxyapatite-Coated Abutments Compared to Traditional Percutaneous Bone Conduction Hearing Implant Surgery-A Pragmatic Multi-Center Randomized Controlled Trial.

Background: Soft tissue preservation using a hydroxyapatite-coated abutment in bone conduction hearing implant surgery may lead to improved clinical outcomes over the short (1 year) and long term (3 years). Methods: In this open multi-center, randomized (1:1), controlled clinical trial, subjects with conductive, mixed hearing loss or single-sided sensorineural deafness were randomly assigned to receive the conventional intervention, a titanium abutment with soft tissue reduction surgery (control), or a new intervention, a hydroxyapatite-coated abutment with soft tissue preservation surgery (test). The primary efficacy outcome was the combined endpoint of numbness, pain, peri-abutment dermatitis, and soft tissue thickening/overgrowth after 1 and 3 years. Results: The Intention-to-treat (ITT) population consisted of 52 control subjects and 51 test subjects. The difference between the groups after 1 year of follow-up as measured by the primary efficacy outcome was not statistically significant (p = 0.12) in the ITT population (n = 103), but did reach statistical significance (p = 0.03) in the per-protocol (PP) population (n = 96). It showed an advantage for the test group, with over twice as many subjects (29%) without these medical events during the first year compared to the control group (13%). After 3 years, the difference between the two groups had declined and did not reach statistical significance (24 vs. 10%, ITT p = 0.45). Secondary outcome measures which showed a statistical significant difference during the first year, such as surgical time (15 vs. 25 minutes, p < 0.0001), numbness (90 vs. 69% of subjects experienced no numbness at 1 year, p < 0.01), neuropathic pain at 3 months (p = 0.0087) and the overall opinion of the esthetic outcome (observer POSAS scale at 3 months, p < 0.01) were favorable for the test group. More soft tissue thickening/overgrowth was observed at 3 weeks for the test group (p = 0.016). Similar results were achieved for the long term follow up. Conclusions: Soft tissue preservation with a hydroxyapatite-coated abutment leads to a reduction in the combined occurrence of complications over the first year which is not statistically significant in the ITT population but is in the PP population. This effect decreased for the long-term study follow up of 3 years and did also not reach statistical significance.

A comparison of international clinical practice guidelines on adult chronic rhinosinusitis shows considerable variability of recommendations for diagnosis and treatment.

OBJECTIVES: To compare international clinical practice guidelines on adult chronic rhinosinusitis (CRS). DESIGN: Extensive literature search in Embase, PubMed and the internet (Google, websites of well-known guideline organizations) on November 21st 2018. MAIN OUTCOME MEASURES: Guidelines' quality was measured by the AGREE II instrument. A summary and comparison of recommendations on diagnosis and treatment with harmonized levels of evidence (LoE) and grade of recommendations (GoR) is given. RESULTS: We selected ten guidelines on CRS. Five guidelines were of sufficient to high quality according to AGREE II, the remaining guidelines predominantly did not meet AGREE II criteria. We harmonized all guideline recommendations so we could compare them, although three guidelines did not provide a LoE. Five guidelines provided recommendations on diagnosis, all of them recommended performing nasal endoscopy, CT scan and allergy testing (with varying GoRs). All ten guidelines provided recommendations on therapy, one treatment, i.e., the use of intranasal steroids, was recommended by all guidelines (with varying GoRs). Recommendations for surgical treatment of CRS were provided by five guidelines. CONCLUSION: We performed an extensive search and included ten (inter)national guidelines on CRS for adults. According to AGREE II, five were of good or sufficient quality. Overall, there was much variation between guidelines in recommended diagnostic test or treatment, direction of evidence and GoR. We found consensus for nasal endoscopy, CT scan, allergy testing and intranasal steroids. We argue for standardization of guideline development, to increase their quality and improve comparability.

Investigating the race for the surface and skin integration in clinically retrieved abutments with two-photon microscopy.

Bone conduction hearing implants can rehabilitate some types of hearing loss. A hydroxyapatite (HA)-coated skin-penetrating abutment was developed to allow for soft tissue preservation and increased skin-abutment adherence. Inflammation is thought to relate to bacterial infection of pockets around the abutment. Upon integration, the host's ability to cover the abutment surface ("race for the surface"), and thus control and prevent competitive bacteria from colonizing it, is improved. However, the attachment mechanisms behind it are not clear. In this study, we applied two-photon microscopy to visualize tissue attachment on abutments retrieved from patients. Skin integration markers were validated and applied to four HA-coated abutments. Evidence of skin integration was found, including the presence of hemidesmosomes, a basement membrane, dermal collagen and vascularization. Cases with clinical signs of severe inflammation and evident biofilm formation showed limited skin integration based on these indicators, confirming the applicability of the "race for the surface" model.

An Exploratory Study to Detect Ménière's Disease in Conventional MRI Scans Using Radiomics.

OBJECTIVE: The purpose of this exploratory study was to investigate whether a quantitative image analysis of the labyrinth in conventional magnetic resonance imaging (MRI) scans using a radiomics approach showed differences between patients with Ménière's disease (MD) and the control group. MATERIALS AND METHODS: In this retrospective study, MRI scans of the affected labyrinths of 24 patients with MD were compared to the MRI scans of labyrinths of 29 patients with an idiopathic asymmetrical sensorineural hearing loss. The 1.5- and 3-T MRI scans had been previously made in a clinical setting between 2008 and 2015. 3D Slicer 4.4 was used to extract several substructures of the labyrinth. A quantitative analysis of the normalized radiomic image features was performed in Mathematica 10. The image features of the two groups were statistically compared. RESULTS: For numerous image features, there was a statistically significant difference (p-value <0.05) between the MD group and the control group. The statistically significant differences in image features were localized in all the substructures of the labyrinth: 43 in the anterior semicircular canal, 10 in the vestibule, 22 in the cochlea, 12 in the posterior semicircular canal, 24 in the horizontal semicircular canal, 11 in the common crus, and 44 in the volume containing the reuniting duct. Furthermore, some figures contain vertical or horizontal bands (three or more statistically significant image features in the same image feature). Several bands were seen: 9 bands in the anterior semicircular canal, 1 band in the vestibule, 3 bands in the cochlea, 0 bands in the posterior semicircular canal, 5 bands in the horizontal semicircular canal, 3 bands in the common crus, and 10 bands in the volume containing the reuniting duct. CONCLUSION: In this exploratory study, several differences were found in image features between the MD group and the control group by using a quantitative radiomics approach on high resolution T2-weighted MRI scans of the labyrinth. Further research should be aimed at validating these results and translating them in a potential clinical diagnostic method to detect MD in MRI scans.

Vestibular assistance systems: promises and challenges.

The handicap resulting from a bilateral vestibular deficit is often underestimated. In most cases the deficit settles gradually. Patients do not understand what is happening to them and have many difficulties to describe their symptoms. They have to consult several doctors with different medical specialties before diagnosis. Once the diagnosis is made there is no biological way to "repair" the deficient vestibular apparatus and vestibular exercises are mildly effective. Attempts have been made to help patients using substitution devices replacing the defective vestibular information by tactile or acoustic cues. Currently, efforts are being made towards the development of a vestibular implant, conceptually similar to the cochlear implant for the rehabilitation of deaf patients. In recent years, several experiments on animal models have demonstrated the feasibility of this project. This paper reports the steps accomplished in human experiments and the main results obtained in our laboratory.

Bilateral Vestibular Hypofunction: Insights in Etiologies, Clinical Subtypes, and Diagnostics.

OBJECTIVE: To evaluate the different etiologies and clinical subtypes of bilateral vestibular hypofunction (BVH) and the value of diagnostic tools in the diagnostic process of BVH. MATERIALS AND METHODS: A retrospective case review was performed on 154 patients diagnosed with BVH in a tertiary referral center, between 2013 and 2015. Inclusion criteria comprised (1) imbalance and/or oscillopsia during locomotion and (2) summated slow phase velocity of nystagmus of less than 20°/s during bithermal caloric tests. RESULTS: The definite etiology of BVH was determined in 47% of the cases and the probable etiology in 22%. In 31%, the etiology of BVH remained idiopathic. BVH resulted from more than 20 different etiologies. In the idiopathic group, the percentage of migraine was significantly higher compared to the non-idiopathic group (50 versus 11%, p < 0.001). Among all patients, 23.4% were known with autoimmune disorders in their medical history. All four clinical subtypes (recurrent vertigo with BVH, rapidly progressive BVH, slowly progressive BVH, and slowly progressive BVH with ataxia) were found in this population. Slowly progressive BVH with ataxia comprised only 4.5% of the cases. The head impulse test was abnormal in 94% of the cases. The torsion swing test was abnormal in 66%. Bilateral normal hearing to moderate hearing loss was found in 49%. Blood tests did not often contribute to the determination of the etiology of the disease. Abnormal cerebral imaging was found in 21 patients. CONCLUSION: BVH is a heterogeneous condition with various etiologies and clinical characteristics. Migraine seems to play a significant role in idiopathic BVH and autoimmunity could be a modulating factor in the development of BVH. The distribution of etiologies of BVH probably depends on the clinical setting. In the diagnostic process of BVH, the routine use of some blood tests can be reconsidered and a low-threshold use of audiometry and cerebral imaging is advised. The torsion swing test is not the "gold standard" for diagnosing BVH due to its lack of sensitivity. Future diagnostic criteria of BVH should consist of standardized vestibular tests combined with a history that is congruent with the vestibular findings.

Honey and beehive products in otorhinolaryngology: a narrative review.

BACKGROUND: Honey and beehive products were rediscovered as an alternative treatment in wounds. The medicinal properties also raised interest of their use in Otorhinolaryngology. OBJECTIVE OF REVIEW: To give an overview of the effectiveness of beehive products in Otorhinolaryngology. TYPE OF REVIEW: Narrative. SEARCH STRATEGY AND EVALUATION: A literature search of the databases PubMed, EMBASE and Cochrane was performed from the last two decades till December 2014. The search terms 'honey', 'propolis' or 'royal jelly' were used. Articles, which evaluated the effectiveness of beehive products in Otorhinolaryngology, were included. The quality assessment of included studies was performed using the Cochrane Collaboration's risk of bias tool. DISCUSSION AND CONCLUSION: A total of 36 studies were identified and evaluated. Eighteen studies investigated their effect in oral infections, seven in infection of the respiratory tract, six in rhino-sinusal diseases, four investigated the use in tonsillectomy and head and neck surgery and one study explored the preventive effect in otitis media. Honey can be considered as effective (additional) treatment in mucositis, childhood cough, persistent post-infectious cough and after tonsillectomy. Propolis may have a role in the treatment of (aphthous) stomatitis, mouth ulcer and prevention of acute otitis media. Royal jelly showed to reduce mucositis. In the presented studies, beehive products proved to be safe, with only minor adverse reactions. Studies showed to be diverse and had some methodological limitations.

The occurrence of tinnitus after CI surgery in patients with severe hearing loss: A retrospective study.

OBJECTIVE: An often reported side-effect of a cochlear implant (CI) is suppression of tinnitus. However, induction of tinnitus is also a known complication of CI surgery. To date, it remains unclear why some CI recipients experience larger tinnitus complaints due to CI surgery while most others do not. The goal of this study was to investigate the effect of deterioration of residual hearing due to CI surgery on tinnitus. DESIGN: In this retrospective database study, pre- and postoperative audiometric hearing thresholds were retrieved from patients' clinical files. Furthermore, tinnitus questionnaires were sent to all patients who fitted inclusion criteria. STUDY SAMPLE: Of the 512 CI patients who were implanted within the last ten years, 197 patients fitted the inclusion criteria and returned the questionnaires. RESULTS: We identified 39 cases (19.8%) who suffered from a newly developed (25) or deteriorated (14) tinnitus following CI surgery. No statistically significant association between perioperative deterioration of hearing thresholds measured by pure-tone audiometry and the development or deterioration of tinnitus was found. CONCLUSIONS: There is a small risk for deteriorated residual hearing after cochlear implantation. However, for patients with preoperative residual hearing, there appears to be no increased risk of developing chronic tinnitus after hearing deterioration due to cochlear implantation.

Deep brain stimulation in tinnitus: current and future perspectives.

Chronic tinnitus, also known as ringing in the ears, affects up to 15% of the adults and causes a serious socio-economic burden. At present, there is no treatment available which substantially reduces the perception of this phantom sound. In the past few years, preclinical and clinical studies have unraveled central mechanisms involved in the pathophysiology of tinnitus, replacing the classical periphery-based hypothesis. In subcortical auditory and non-auditory regions, increased spontaneous activity, neuronal bursting and synchrony were found. When reaching the auditory cortex, these neuronal alterations become perceptually relevant and consequently are perceived as phantom sound. A therapy with a potential to counteract deeply located pathological activity is deep brain stimulation, which has already been demonstrated to be effective in neurological diseases such as Parkinson's disease. In this review, several brain targets are discussed as possible targets for deep brain stimulation in tinnitus. The potential applicability of this treatment in tinnitus is discussed with examples from the preclinical field and clinical case studies.

Vestibular implants: Hope for improving the quality of life of patients with bilateral vestibular loss.

The vestibular system plays an essential role in crucial tasks such as postural control, gaze stabilization, and spatial orientation. Currently, there is no effective treatment for a bilateral loss of the vestibular function (BVL). The quality of life of affected patients is significantly impaired. During the last decade, our group has explored the potential of using electrical stimulation to artificially restore the vestibular function. Our vestibular implant prototype consists of a custom modified cochlear implant featuring one to three vestibular electrodes implanted in the proximity of the ampullary branches of the vestibular nerve; in addition to the main cochlear array. Special surgical techniques for safe implantation of these devices have been developed. In addition, we have developed stimulation strategies to generate bidirectional eye movements as well as the necessary interfaces to capture the signal from a motion sensor (e.g., gyroscope) and use it to modulate the stimulation signals delivered to the vestibular nerves. To date, 24 vestibular electrodes have been implanted in 11 BVL patients. Using a virtual motion profile to modulate the "baseline" electrical stimulation, vestibular responses could be evoked with 21 electrodes. Eye movements with mean peak eye velocities of 32°/s and predominantly in the plane of the stimulated canal were successfully generated. These are within the range of normal compensatory eye movements during walking and were large enough to have a significant effect on the patients' visual acuity. These results indicate that electrical stimulation of the vestibular nerve has a significant functional impact; eye movements generated this way could be sufficient to restore gaze stabilization during essential everyday tasks such as walking. The innovative concept of the vestibular implant has the potential to restore the vestibular function and have a central role in improving the quality of life of BVL patients in the near future.

Comparison of two cochlear implantation techniques and their effects on the preservation of residual hearing. Is the surgical approach of any importance?

The goal of this work was to review the pre-and postsurgical auditory thresholds of two surgical implantation techniques, namely the mastoidectomy with posterior tympanotomy approach (MPTA) and suprameatal approach (SMA), to determine whether there is a difference in the degree of preservation of residual hearing. In a series of 430 consecutive implanted patients 227 patients had measurable pre-operative hearing thresholds at 250, 500, and 1,000 Hz. These patients were divided into two groups according to the surgical technique that was used for implantation. The SMA approach was followed for 84 patients in Amsterdam, whereas the MPTA technique was adhered to 143 patients in Maastricht. The outcome variables of interest were alteration of pre-and postoperative auditory thresholds after cochlear implantation. Complete or partial preservation of residual hearing was obtained in 21.4 and 21.7% in the SMA and MPTA group, respectively. No statistical differences could be found between the SMA and MPTA group (p = 0.96; Chi-square test). The SMA technique is correlated with a similar degree of hearing loss after cochlear implantation compared to the MPTA technique. However, both techniques were not able to conserve a measurable amount of hearing in patients with a substantial degree of residual hearing. Therefore, both surgical techniques need to be refined for patients in which residual acoustical hearing is pursued.

Sclerosing bone dysplasias with involvement of the craniofacial skeleton.

In this review we provide a complete overview of the existing sclerosing bone dysplasias with craniofacial involvement. Clinical presentation, disease course, the craniofacial symptoms, genetic transmission pattern and pathophysiology are discussed. There is an emphasis on radiologic features with a large collection of CT and MRI images. In previous reviews the craniofacial area of the sclerosing bone dysplasias was underexposed. However, craniofacial symptoms are often the first symptoms to address a physician. The embryology of the skull and skull base is explained and illustrated for a better understanding of the affected areas.

Localization of the gene for hyperostosis cranialis interna to chromosome 8p21 with analysis of three candidate genes.

Hyperostosis cranialis interna (HCI) is a rare autosomal dominant disorder characterized by intracranial hyperostosis and osteosclerosis, which is confined to the skull, especially the calvarium and the skull base. The rest of the skeleton is not affected. Progressive bone overgrowth causes nerve entrapment that leads to recurrent facial nerve palsy, disturbance of the sense of smell, hearing and vision impairments, impairment of facial sensibility, and disturbance of balance due to vestibular areflexia. The treatment is symptomatic. Histomorphological investigations showed increased bone formation with a normal tissue structure. Biochemical parameters were normal. Until today the disease has been described in only three related Dutch families with common progenitors and which consist of 32 individuals over five generations. HCI was observed in 12 family members over four generations. Patients are mildly to severely affected. Besides HCI, several bone dysplasias with hyperostosis and sclerosis of the craniofacial bones are known. Examples are Van Buchem disease, sclerosteosis, craniometaphyseal dysplasia, and Camurati-Engelmann disease. However, in these cases the long bones are affected as well. Linkage analysis in a family with HCI resulted in the localization of the disease-causing gene to a region on chromosome 8p21 delineated by markers D8S282 and D8S382. Interesting candidate genes in this region are BMP1, LOXL2, and ADAM28. Sequence analysis of these genes did not reveal any putative mutations. This suggests that a gene not previously involved in a sclerosing bone dysplasia is responsible for the abnormal growth in the skull of these patients.