Seventeen children at six institutions with neurofibromatosis type 2 (NF2)-related vestibular schwannomas received bevacizumab. Eight of the 13 patients with initial hearing loss (61%) showed objective hearing improvement within six months of treatment. No patients showed hearing deterioration during therapy; however, only two patients showed objective radiological response. Seven of eight patients had tumor progression or worsening hearing loss upon cessation of treatment. Bevacizumab was well tolerated with no patients discontinuing therapy. Bevacizumab appears to postpone hearing loss in childhood NF2-associated vestibular schwannomas, but responses are not durable, suggesting that either longer maintenance therapy or new strategies are required.

• MeSH
• bevacizumab aplikace a dávkování   MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• neurofibromin 2 metabolismus   MeSH
• vestibulární schwannom farmakoterapie   metabolismus   patologie   patofyziologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

• MeSH
• ependymom diagnóza   genetika   MeSH
• lidé MeSH
• mladiství MeSH
• neurofibromatóza 2 diagnóza   genetika   MeSH
• vrozené, dědičné a novorozenecké nemoci a abnormality diagnóza   genetika   komplikace   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• abstrakt z konference MeSH
• kazuistiky MeSH

Dendritic cell neurofibroma with pseudorosettes (DCNWPR) is a recently proposed variant of neurofibroma with a distinctive microscopic appearance that is produced by a pseudorosette pattern formed by small, dark, lymphocyte-like cells (Type I cells) arranged concentrically around larger cells, with pale-staining vesicular nuclei and copious faintly eosinophilic cytoplasm (Type II cells). Although DCNWPR appears not to be associated with neurofibromatosis (NF), 1 patient with DCNWPR has been described and suggested to have a form of NF because of multiple skin lesions, with 2 of them being DCNWPR as confirmed histologically. The aim of this study was to find out whether the neurofibromatosis type 2 (NF2) gene is mutated in DCNWPR. Seven histologically proven cases of DCNWPR, from which a substantial amount of archival paraffin-embedded material was available, were selected for this study. Three cases have been previously reported, including the intraneural lesion, and 4 cases were newly identified. There were 3 female and 4 male patients, ranging in age from 30 to 61 years (median, 48 yrs). All patients clinically presented with a small solitary lesion that was clinically diagnosed as fibroma or neurofibroma, and none of the patients had signs of NF. Follow-up was known for 6 patients (range, 1-5 yrs; median, 2.5 yrs) and was uneventful in each case. Microscopically, all lesions fulfilled the criteria for DCNWPR. Exons 1 to 15 of the NF2 gene were amplified by PCR using primers previously published. The amplified fragments were purified and sequenced. The obtained sequences were computer analyzed and compared with the data of the GenBank database. No mutation was identified in 5 analyzed samples from which suitable DNA had been extracted. DCNWPR appears to have no mutation in exons 1-15 of the NF2 gene. Given the relatively small number of cases studied, it seems premature to declare that a mutation of the NF2 gene is not involved in DCNWPR, as the possibility cannot be excluded that mutations were present but remained undetected because they occurred in exons that were not examined.

• MeSH
• dendritické buňky patologie   MeSH
• dospělí MeSH
• exony MeSH
• geny neurofibromatózy 2 MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• neurofibrom genetika   patologie   MeSH
• polymerázová řetězová reakce MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

• Publikační typ
• abstrakt z konference MeSH

Neurofibromatosis type 2 (NF-2) is a dominantly inherited genetic disorder that results from variants in the tumor suppressor gene, neurofibromin 2 (NF2). Here, we report the generation of a conditional zebrafish model of neurofibromatosis established by inducible genetic knockout of nf2a/b, the zebrafish homologs of human NF2. Analysis of nf2a and nf2b expression revealed ubiquitous expression of nf2b in the early embryo, with overlapping expression in the neural crest and its derivatives and in the cranial mesenchyme. In contrast, nf2a displayed lower expression levels. Induction of nf2a/b knockout at early stages increased the proliferation of larval Schwann cells and meningeal fibroblasts. Subsequently, in adult zebrafish, nf2a/b knockout triggered the development of a spectrum of tumors, including vestibular Schwannomas, spinal Schwannomas, meningiomas and retinal hamartomas, mirroring the tumor manifestations observed in patients with NF-2. Collectively, these findings highlight the generation of a novel zebrafish model that mimics the complexities of the human NF-2 disorder. Consequently, this model holds significant potential for facilitating therapeutic screening and elucidating key driver genes implicated in NF-2 onset.

• MeSH
• dánio pruhované * genetika   embryologie   MeSH
• geneticky modifikovaná zvířata MeSH
• genový knockout * MeSH
• larva metabolismus   MeSH
• lidé MeSH
• modely nemocí na zvířatech * MeSH
• neurofibromatóza 2 genetika   patologie   metabolismus   MeSH
• neurofibromatózy genetika   patologie   metabolismus   MeSH
• neurofibromin 2 * genetika   metabolismus   nedostatek   MeSH
• proliferace buněk MeSH
• proteiny dánia pruhovaného * genetika   metabolismus   nedostatek   MeSH
• Schwannovy buňky metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Východisko. Sluchová kmenová neuroprotéza (auditory brainstemimplant –ABI) je elektroprotetické zařízení, které zprostředkuje zvukové vjemy neslyšícím nemocným s oboustrannou poruchou funkce sluchového nervu. Dráždění sluchových jader na spodině IV. mozkové komory je uskutečněno pomocí destičky s elektrodami, která se v průběhu operace zavádí do laterálního recesu IV. komory. Metody a výsledky. Hlavní indikační skupinu pro sluchovou kmenovou neuroprotézu představují pacienti s neurofibromatózou 2. typu (NF2) s oboustrannými vestibulárními schwannomy. Při chirurgickém odstranění tumorů dochází k oboustrannému porušení funkce a často i integrity sluchového nervu, proto lze po ablaci nádoru aplikovat v jedné době sluchovou kmenovou neuroprotézu. Implantovaní používají neuroprotézu většinou jako pomůcku při odezírání, výjimečně jsou schopni rozumět řeči i bez zrakové kontroly. Program implantace kmenových neuroprotéz byl v České republice zahájen v roce 1999. Šlo o vůbec první implantaci ABI ve střední Evropě. Od této doby do současnosti byla sluchová kmenová neuroprotéza operována celkem u 5 pacientů, z nichž první čtyři pacienti používají neuroprotézu delší dobu. U poslední operované nebyl dosud zapojen řečový procesor vzhledem ke krátké době, která uplynula od operace. Závěry. Lze konstatovat, že u všech operovaných je kmenová neuroprotéza přínosem. U jednoho pacienta lze hovořit o signifikantnímpřínosu, neboť dokáže rozumět řeči bez zrakových vodítek, ostatní operovaní používají neuroprotézu jako pomůcku při odezírání. U jedné nemocné je efekt implantátu výrazně omezen motorickým hendikapem po resekci větší částí mozečku. Nemocná ABI sice používá, kontakt s ní je však velmi obtížný.

Background. Auditory brainstem implant (ABI) is an electroprosthetic device enabling sound sensations in deaf persons with a bilateral lesion of auditory nerves. Stimulation of auditory nuclei in the floor of the IVth ventricle is realized by an electrode array introduced during surgery in the lateral recess of the IVth ventricle. Methods and Results. The main indication group for ABI is represented by patients with neurofibromatosis 2 (NF2) suffering from bilateral vestibular schwannomas. During surgery aimed at tumour removal, auditory nerve function and integrity are almost always destroyed, therefore, an ABI can be introduced as an one stage procedure. Implantees use the device mainly as the aid in lipreading, only very rarely they can comprehend speech without visual cues. Auditory brainstem implant programme has been introduced in the Czech Republic in the year 1999. It was the very first ABI surgery in the Central Europe. Since that time, 5 patients had received the auditory brainstem implant, from which the first four use the device for a longer time. Conclusions. The last operated patient has not been activated yet. It may be said, that ABI represents a benefit to all our patients, in one implanted this benefit is significant, since he can understand speech without lipreading, the other implantees use the device as an aid in lipreading. In one female patient, the device benefit is severely limited by a motoric handicap after partial cerebellar resection during surgery. Nevertheless, she uses the implant on a daily basis, but contact with her is limited and difficult.

• MeSH
• dospělí MeSH
• finanční podpora výzkumu jako téma MeSH
• hluchota diagnóza   chirurgie   MeSH
• implantované elektrody MeSH
• kochleární implantace metody   MeSH
• lidé MeSH
• neurilemom chirurgie   MeSH
• neurofibromatóza 2 MeSH
• protézy a implantáty MeSH
• sluchové evokované potenciály MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• přehledy MeSH
• srovnávací studie MeSH

Neurofibromatóza je relativně časté autozomálně dominantně dědičné neurokutánní onemocnění způsobené mutací tumor supresorových genů se vznikem mnohočetných hamartomů, benigních a maligních nádorů. Onemocnění se v současné době dělí na 3 samostatné jednotky s odlišným klinickým obrazem, podmíněným mutací různých genů – neurofibromatózu typu 1 (NF1), neurofibromatózu typu 2 (NF2) a schwannomatózu. Nejčastějším typem je NF1. Projevy onemocnění jsou věkově vázané, závažnost klinického obrazu je variabilní. Kožní projevy se vyskytují zejména u NF1, méně u ostatních typů. Jedná se o mnohočetné skvrny charakteru „café-au-lait“ a drobné skvrnité hyperpigmentace („freckling“) v axillách a tříslech. U NF1 se nachází neurofibromy a plexiformní neurofibromy, gliomy optiku, patognomický je nález Lischových nodulů na duhovce. U NF2 se nachází vestibulární schwannomy, u schwannomatózy mnohočetné schwannomy periferních nervů. Prognóza je individuální podle klinického obrazu a komplikací. K diagnostice jednotlivých forem neurofibromatóz slouží diagnostická kritéria, klíčovou roli hraje vyšetření dermatologem. Pacienti by měli být koncentrováni ve specializovaných centrech. Léčba neurofibromatózy je symptomatická. Klíčová slova: neurofibromatóza – café-au-lait – freckling – neurofibrom – schwannom – gliom – specializovaná centra odborné péče

Neurofibromatosis is a relatively common autosomal dominant hereditary neuro-cutaneous disease caused by mutation in tumor-suppressor genes. It results in the development of multiple hamartomas, benign and malignant tumors. The disease is currently classified into 3 individual subunits with different clinical presentations based on mutations of different genes – neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis. The most common type is NF1. The symptoms are age-dependent, the severity of clinical picture is variable. Cutaneous symptoms are present namely in NF1, they are less common in other types. They include multiple café-au-lait spots and axillary and inguinal freckling. Neurofibromas, plexiform neurofibromas and optic gliomas are present in NF1, Lisch nodules in the iris are pathognomonic. Vestibular schwannomas are typical for NF2, and multiple schwannomas in peripheral nerves are present in schwannomatosis. The prognosis differs and is based on the clinical picture and complications. Diagnostic criteria play a key role in differentiating various types of neurofibromatosis and dermatological examination plays a key role. Patients should be concentrated in specialized centers. The treatment of neurofibromatosis is symptomatic. Key words: neurofibromatosis – café-au-lait spot – freckling – neurofibroma – schwannoma – glioma – specialized centers specialized care

• Klíčová slova
• freckling, schwannomatóza,
• MeSH
• diferenciální diagnóza MeSH
• dlouhodobá péče MeSH
• genetické testování MeSH
• gliom zrakového nervu etiologie   MeSH
• hyperpigmentace etiologie   komplikace   MeSH
• lidé MeSH
• mezioborová komunikace MeSH
• nádory centrálního nervového systému komplikace   MeSH
• nádory komplikace   MeSH
• nemoci centrálního nervového systému komplikace   MeSH
• nemoci duhovky komplikace   MeSH
• nemoci kostí komplikace   MeSH
• neurilemom etiologie   komplikace   MeSH
• neurofibrom etiologie   komplikace   MeSH
• neurofibromatóza 1 * diagnóza   etiologie   patofyziologie   terapie   MeSH
• neurofibromatóza 2 diagnóza   etiologie   patofyziologie   MeSH
• neurofibromatózy klasifikace   MeSH
• neurofibrosarkom komplikace   MeSH
• plexiformní neurofibrom etiologie   MeSH
• skvrny bílé kávy etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: Vestibular schwannomas (VSs) related to neurofibromatosis type 2 (NF2) are challenging tumors. The increasing use of stereotactic radiosurgery (SRS) necessitates further investigations of its role and safety. OBJECTIVE: To evaluate tumor control, freedom from additional treatment (FFAT), serviceable hearing preservation, and radiation-related risks of patients with NF2 after SRS for VS. METHODS: We performed a retrospective study of 267 patients with NF2 (328 VSs) who underwent single-session SRS at 12 centers participating in the International Radiosurgery Research Foundation. The median patient age was 31 years (IQR, 21-45 years), and 52% were male. RESULTS: A total of 328 tumors underwent SRS during a median follow-up time of 59 months (IQR, 23-112 months). At 10 and 15 years, the tumor control rates were 77% (95% CI: 69%-84%) and 52% (95% CI: 40%-64%), respectively, and the FFAT rate were 85% (95% CI: 79%-90%) and 75% (95% CI: 65%-86%), respectively. At 5 and 10 years, the serviceable hearing preservation rates were 64% (95% CI: 55%-75%) and 35% (95% CI: 25%-54%), respectively. In the multivariate analysis, age (hazards ratio: 1.03 [95% CI: 1.01-1.05]; P = .02) and bilateral VSs (hazards ratio: 4.56 [95% CI: 1.05-19.78]; P = .04) were predictors for serviceable hearing loss. Neither radiation-induced tumors nor malignant transformation were encountered in this cohort. CONCLUSION: Although the absolute volumetric tumor progression rate was 48% at 15 years, the rate of FFAT related to VS was 75% at 15 years after SRS. None of the patients with NF2-related VS developed a new radiation-related neoplasm or malignant transformation after SRS.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádorová transformace buněk MeSH
• následné studie MeSH
• nedoslýchavost * chirurgie   MeSH
• neurofibromatóza 2 * komplikace   chirurgie   MeSH
• radiochirurgie * škodlivé účinky   MeSH
• retrospektivní studie MeSH
• vestibulární schwannom * komplikace   radioterapie   chirurgie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: Convexity meningiomas are common tumors requiring treatment in patients with neurofibromatosis type 2 (NF2). Although different therapeutic options are described for sporadic convexity meningioma, much less is known about these lesions in patients with NF2 despite their distinct biology and need for multiple treatments. We analyzed the value of Gamma Knife radiosurgery (GKRS) as definitive treatment for convexity meningiomas in patients with NF2. METHODS: This international multicenter retrospective study was approved by the International Radiosurgery Research Foundation. Patients with NF2 with at least 1 convexity meningioma and 6-month follow-up after primary GKRS were included. RESULTS: Inclusion criteria were met by 18 patients with NF2. A total of 120 convexity meningiomas (median treatment volume, 0.66 cm3 [range, 0.10-21.20 cm3]) were analyzed. Median follow-up after initial GKRS was 15.6 years (range, 0.6-25.5 years). Median age at GKRS was 32.5 years (range, 16-53 years). Median number of meningiomas per patient was 13 (range, 1-27), and median number of convexity lesions receiving GKRS per patient was 3.5 (range, 1-27). One case of tumor progression was reported 24 years after GKRS, leading to actuarial progression-free survival rates of 100% at 2, 5, and 10 years. No malignant transformation or death due to meningioma or radiosurgery was recorded. CONCLUSIONS: GKRS is safe and effective as definitive treatment of small to medium-sized convexity meningiomas in patients with NF2. Despite concerns about the particular mutational burden of these tumors, no malignant transformation manifested after treatment. GKRS represents a minimally invasive option that offers long-term tumor control to this specific group of patients.

• MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• edém mozku etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• meningeální nádory komplikace   patologie   radioterapie   MeSH
• meningeom komplikace   patologie   radioterapie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mnohočetné primární nádory komplikace   radioterapie   MeSH
• neurofibromatóza 2 komplikace   MeSH
• radiochirurgie škodlivé účinky   metody   MeSH
• retrospektivní studie MeSH
• tumor burden MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: The management of neurofibromatosis type 2 (NF2)-associated meningiomas is challenging. The role of Gamma Knife radiosurgery (GKRS) in the treatment of these tumors remains to be fully defined. In this study, the authors aimed to examine the role of GKRS in the treatment of NF2-associated meningiomas and to evaluate the outcomes and complications after treatment. METHODS: Seven international medical centers contributed data for this retrospective cohort. Tumor progression was defined as a ≥ 20% increase from the baseline value. The clinical features, treatment details, outcomes, and complications were studied. The median follow-up was 8.5 years (range 0.6-25.5 years) from the time of initial GKRS. Shared frailty Cox regression was used for analysis. RESULTS: A total of 204 meningiomas in 39 patients treated with GKRS were analyzed. Cox regression analysis showed that increasing the maximum dose (p = 0.02; HR 12.2, 95% CI 1.287-116.7) and a lower number of meningiomas at presentation (p = 0.03; HR 0.9, 95% CI 0.821-0.990) were predictive of better tumor control in both univariable and multivariable settings. Age at onset, sex, margin dose, location, and presence of neurological deficit were not predictive of tumor progression. The cumulative 10-year progression-free survival was 94.8%. Radiation-induced adverse effects were noted in 4 patients (10%); these were transient and managed medically. No post-GKRS malignant transformation was noted in 287 person-years of follow-up. CONCLUSIONS: GKRS achieved effective tumor control with a low and generally acceptable rate of complications in NF2-associated meningiomas. There did not appear to be an appreciable risk of post-GKRS-induced malignancy in patients with NF2-treated meningiomas.

• MeSH
• dítě MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• meningeom etiologie   chirurgie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory mozku etiologie   chirurgie   MeSH
• následné studie MeSH
• nemoci nervového systému etiologie   MeSH
• neurofibromatóza 2 komplikace   MeSH
• progrese nemoci MeSH
• radiochirurgie škodlivé účinky   metody   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• věk při počátku nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH