Cerebellar mutism syndrome in children with brain tumours of the posterior fossa.

BACKGROUND: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has been reported in up to 39% of the patients but the exact incidence is uncertain since milder cases may be unrecognized. Recovery is usually incomplete. Reported risk factors are tumour type, midline location and brainstem involvement, but the exact aetiology, surgical and other risk factors, the clinical course and strategies for prevention and treatment are yet to be determined. METHODS: This observational, prospective, multicentre study will include 500 children with posterior fossa tumours. It opened late 2014 with participation from 20 Nordic and Baltic centres. From 2016, five British centres and four Dutch centres will join with a total annual accrual of 130 patients. Three other major European centres are invited to join from 2016/17. Follow-up will run for 12 months after inclusion of the last patient. All patients are treated according to local practice. Clinical data are collected through standardized online registration at pre-determined time points pre- and postoperatively. Neurological status and speech functions are examined pre-operatively and postoperatively at 1-4 weeks, 2 and 12 months. Pre- and postoperative speech samples are recorded and analysed. Imaging will be reviewed centrally. Pathology is classified according to the 2007 WHO system. Germline DNA will be collected from all patients for associations between CMS characteristics and host genome variants including pathway profiles. DISCUSSION: Through prospective and detailed collection of information on 1) differences in incidence and clinical course of CMS for different patient and tumour characteristics, 2) standardized surgical data and their association with CMS, 3) diversities and results of other therapeutic interventions, and 4) the role of host genome variants, we aim to achieve a better understanding of risk factors for and the clinical course of CMS - with the ultimate goal of defining strategies for prevention and treatment of this severely disabling condition. TRIAL REGISTRATION: Clinicaltrials.gov : NCT02300766 , date of registration: November 21, 2014.

Effect of bevacizumab on intracranial meningiomas in patients with neurofibromatosis type 2 - a retrospective case series.

PURPOSE: The hallmark of neurofibromatosis type 2 (NF2) is bilateral vestibular schwannomas (VS). Approximately 80% of NF2 patients also have intracranial meningiomas. Vascular endothelial growth factor (VEGF) is expressed in both NF2-related and sporadic occurring meningiomas and anti-VEGF therapy (bevacizumab) may, therefore, be beneficial in NF2-related meningiomas. The purpose of the study was to report the effect of bevacizumab on meningiomas in NF2 patients. MATERIALS AND METHODS: We retrospectively reviewed the effect of bevacizumab on the cross-sectional area (CSA) of 14 intracranial meningiomas in 7 NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every two weeks for six months and 15 mg/kg every three weeks thereafter. Patients were evaluated according to the modified Macdonald criteria with repeated magnetic resonance (MR) scans. RESULTS: The median duration of therapy was 27 months (range 16-34) and 42 MR scans (median 8, range 4-11) were reviewed. The median annual change in meningioma CSA prior to bevacizumab was 2% (range -4%-+76%). During treatment, a decrease in meningioma CSA was observed in 5 of 14 meningiomas (36%) in 5 of 7 patients (71%). The median decrease in CSA was -10% (range -3%--25%). One meningioma (7%) progressed and the remaining (93%) had stable disease. CONCLUSIONS: Bevacizumab may slow or reverse the growth of some NF-related meningiomas. However, we have previously reported a fatal case of intracerebral hemorrhage following bevacizumab in NF2 patients, wherefore, this effect needs to be balanced carefully against the risk of side effects.

The use of 5-ALA to assist complete removal of residual non-enhancing part of childhood medulloblastoma: a case report.

PURPOSE: Medulloblastoma is the most common malignant brain tumor in childhood. Radical surgery in the non-metastatic stage is an important factor with respect to overall survival. In this case, 5-aminolevulinic acid (5-ALA) was used at second-look surgery in order to improve surgical results. METHODS: The child was pretreated with 3 × 4 mg dexamethasone for 4 days prior to the second surgery. At 5 a.m. on the day of surgery, a freshly prepared solution of 5-ALA (20 mg/kg body weight; Medac, Germany) was given orally. RESULTS: At surgery, through the original opening, the vague red fluorescence of the tumor was clearly distinctive from the cerebellum with no tumor infiltration. All fluorescent tissue was removed. Postoperative MRI gave suspicion of yet at small tumor residue, but this structure is less than 1.5 ml in calculated volume, and consequently the recommended adjuvant therapy of the child changed from the high-risk medulloblastoma regimen to the standard-risk regimen. CONCLUSIONS: In this particular difficult case of non-contrast-enhancing tumor, 5-ALA was of vital importance to improve rate of resection and change the aggressiveness needed in postsurgery radiation therapy.

The effect of bevacizumab on vestibular schwannoma tumour size and hearing in patients with neurofibromatosis type 2.

The hallmark of neurofibromatosis type 2 (NF2) is bilateral vestibular schwannomas (VS) and severe hearing loss is common in NF2 patients. Vascular endothelial growth factor (VEGF) expression level in NF2 correlates with tumour growth rate and bevacizumab, a VEGF-binding antibody, has previously been shown to induce tumour shrinkage and improve hearing. We retrospectively reviewed the effect of bevacizumab on hearing and VS tumour size in 12 consecutive NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every second week for 6 months; hereafter, bevacizumab 15 mg/kg was administered every third week. Patients were evaluated with repeated audiometries, MR scans and clinical evaluations. Radiological response was defined as a 20 % or greater reduction in VS volume. A total of 398 treatments (median 36) were administered and the median duration on therapy was 22 months (range 7-34). We observed a radiological response (≥20 % tumour shrinkage) in seven out of 18 tumours (39 %) in six out of 12 patients (50 %). Sustained radiological responses were maintained in six tumours (33 %) for more than 2 months. Three patients had objectively improved hearing and five patients reported subjective benefit in neurological symptoms, including improved hearing. Toxicity was in general manageable; however, one patient died from cerebral haemorrhage which was possibly related to therapy. In conclusion, bevacizumab improved hearing and reduced the size of VS in some patients with progressive NF2 which corroborates previous findings; however, the risk of severe side effects should be carefully considered and discussed with the patients prior to treatment.

Lyme Neuroborreliosis in a Patient with Breast Cancer: MRI and PET/CT Findings.

We present a case demonstrating the performance of different radiographical and nuclear medicine imaging modalities in the diagnostic work-up of a patient with Lyme neuroborreliosis. The patient presented in late summer 2019 with radicular pains followed by a foot drop and peripheral facial palsy, both right-sided. Due to a history of breast cancer, disseminated malignant disease was initially suspected. Bone metastasis was ruled out by skeletal scintigraphy. Magnetic resonance imaging (MRI) of the neuroaxis and a whole body 18F-FDG PET-CT was performed within 48 hours. The MRI revealed a strong contrast enhancement of the conus medullaris and fibers of the cauda equina, while the 18F-FDG PET/CT was without pathological findings. Examination of cerebrospinal fluid led to the definitive diagnosis of Lyme neuroborreliosis with monocytic pleocytosis and a positive intrathecal test for Borrelia burgdorferi. The patient became pain-free after 10 days of ceftriaxone, and the paralysis slowly regressed the following month. This case highlights the difficulty of the diagnosis of Lyme neuroborreliosis and discusses the relevant imaging findings.

Congenital olfactory impairment is linked to cortical changes in prefrontal and limbic brain regions.

The human sense of smell is closely associated with morphological differences of the fronto-limbic system, specifically the piriform cortex and medial orbitofrontal cortex (mOFC). Still it is unclear whether cortical volume in the core olfactory areas and connected brain regions are shaped differently in individuals who suffer from lifelong olfactory deprivation relative to healthy normosmic individuals. To address this question, we examined if regional variations in gray matter volume were associated with smell ability in seventeen individuals with isolated congenital olfactory impairment (COI) matched with sixteen normosmic controls. All subjects underwent whole-brain magnetic resonance imaging, and voxel-based morphometry was used to estimate regional variations in grey matter volume. The analyses showed that relative to controls, COI subjects had significantly larger grey matter volumes in left middle frontal gyrus and right superior frontal sulcus (SFS). COI subjects with severe olfactory impairment (anosmia) had reduced grey matter volume in the left mOFC and increased volume in right piriform cortex and SFS. Within the COI group olfactory ability, measured with the "Sniffin' Sticks" test, was positively associated with larger grey matter volume in right posterior cingulate and parahippocampal cortices whereas the opposite relationship was observed in controls. Across COI subjects and controls, better olfactory detection threshold was associated with smaller volume in right piriform cortex, while olfactory identification was negatively associated with right SFS volume. Our findings suggest that lifelong olfactory deprivation trigger changes in the cortical volume of prefrontal and limbic brain regions previously linked to olfactory memory.

[Bacterial sacroiliitis caused by group B streptococci].

A 12-year-old girl was admitted to the paediatric department due to a short history of severe pain in the right hip, inability to walk and fever, 39 °C. She had had no previous trauma or ongoing infection elsewhere. Examination showed a septic girl with pain of the right sacroiliac joint. Laboratory findings showed a marginally raised white blood cell count and C-reactive protein. A magnetic resonance imaging was performed and showed effusion of the right sacroiliac joint without root compression. Three days later blood cultures showed group B streptococci and the patient received intravenous antibiotic treatment for two weeks and continued with oral antibiotics for four weeks.