On-site CAD templates reduce surgery time for complex craniostenosis repair in infants: a new method.

INTRODUCTION: The surgical correction of craniostenosis in children is a time-consuming and taxing procedure. To facilitate this procedure, especially in infants with complex craniostenosis, we refined the computer-aided design and manufacturing technique (CAD/CAM) based on computed tomography (CT)-generated DICOM data. We used cutting guides and molding templates, which allowed the surgeon to reshape and fixate the supraorbital bar extracorporeally on a side table and to control the intracorporal fit without removing the template. METHOD AND PATIENTS: To compare our traditional concept with the possibility of preoperative virtual planning (PVP) technique, the surgical treatment and courses of 16 infants with complex craniostenosis following fronto-orbital advancement (FOA) (age range 8-15 months) were analyzed in two groups (group 1: traditional, control group n = 8, group 2: CAD/CAM planned, n = 8). RESULTS: While in both groups, the head accurately reshaped postoperatively during the follow-up; the CAD group 2 showed a significantly shorter operating time with a mean of 4 h 25 min compared with group 1 with a mean of 5 h 37 min (p = 0.038). Additionally, the CAD group 2 had a significantly lower volume of blood loss (380 ml vs. 575 ml mean, p = 0.047), lower blood transfusion volume (285 ml vs. 400 ml mean, p = 0.108), lower fresh frozen plasma (FFP) volume (140 ml vs. 275 ml mean, p = 0.019), shorter stay in the pediatric intensive care unit (PICU) (3 vs. 5 days mean (p = 0.002), and shorter total length of hospital stay (6 days vs. 8 days mean, p = 0.002). CONCLUSION: CAD/CAM cutting guides and templates offer optimizing operative efficiency, precision, and accuracy in craniostenosis surgery in infants. As shown in this single-center observational study, the use of on-site templates significantly accelerates the reconstruction of the bandeau. The virtual 3D planning technique increases surgical precision without discernible detrimental effects.

Optimized surgical treatment for normal pressure hydrocephalus: comparison between gravitational and differential pressure valves.

OBJECTIVES: In idiopathic normal pressure hydrocephalus (NPH) ventriculoperitoneal (VP) shunt insertion is the method of choice to improve cardinal symptoms such as gait disturbance, urge incontinence and/or dementia. With reduced compliance, the brain of the elderly is prone for overdrainage complications. This was especially true with the use of differential pressure valve implantation. The present study compares clinical outcome and complication rates after VP shunt insertion with differential pressure valves in the early years and gravitational valves since 2005. METHODS: The authors reviewed patients treated at our institution for NPH since 1995. Differential pressure valves were solely used in the initial years, while the treatment regimen changed to gravitational valves in 2005. Clinical improvement/surgical success rates as well as complications were compared between the two groups. RESULTS: Eighty-nine patients were enrolled for the present study. Mean age at the time of surgery was 73.5 ± 6.3 years. Male patients predominated with 73, compared with 16 female patients. Median follow-up time was 28 ± 26 months. Date of last follow-up was 1st October 2013. Forty-nine patients received a gravitational valve, while 40 were treated with differential pressure valves. In the gravitational group a significant improvement was observed after shunt insertion for gait disorder, cognitive impairment and urge incontinence (p < 0.0001, resp. p = 0.004), while a significant change in the differential pressure group was only seen for gait disorder (p = 0.03) but not for cognition or urinary incontinency (p > 0.05). The risk of hygroma as a sign of shunt overdrainage requiring surgical intervention was significantly higher in the differential pressure group (5 versus 0 in the gravitational group). CONCLUSIONS: Patients with NPH treated with gravitational valves in the present cohort showed a more profound improvement in their initial symptoms, including gait disorder, cognitive impairment and urinary incontinency without the risk of overdrainage complications requiring surgical intervention when compared with patients who received differential pressure valves in previous years.

[Hydrocephalus in childhood : causes and imaging patterns]. / Hydrozephalus im Kindesalter : Ursachen und bildmorphologische Darstellung.

CLINICAL ISSUE: Causes and imaging patterns of hydrocephalus differ depending on the age of the patient. Traditionally, hydrocephalus was classified into non-communicating and communicating hydrocephalus but more recent classifications also take the site of occlusion and the etiology into account. DIAGNOSTICS: For the diagnostic work-up computed tomography (CT), sonography and magnetic resonance imaging (MRI) are available and MRI is the method of choice for children and adolescents as it allows determination of the cause and location of a possible obstruction. In the first 12-18 months sonography allows evaluation of the lateral ventricles and the third ventricle and CT is usually only chosen in children in emergency situations and/or if no other modality is available. PERFORMANCE: We retrospectively evaluated a population of 785 children and adolescents (426 males aged 0-17 years) referred for MRI between April 2009 and March 2012 due to headaches, somnolence, concentration difficulties or developmental delay. Among these 80 (49 male) met the MRI criteria for hydrocephalus, 75 (46 male) had non-communicating hydrocephalus and 5 (3 male) communicating hydrocephalus. Of the patients 24 (15 male) had posthemorrhagic aqueductal stenosis, 16 (8 male) intracranial tumors, 9 (6 male) Chiari II malformations, 5 (4 male) other congenital malformations including malformations of the Dandy Walker spectrum, 9 (3 male) idiopathic aqueductal stenosis, 7 (5 male) arachnoidal cysts and 10 (8 male) other disorders, such as post-infections, macrocephaly cutis marmorata telangiectatica congenita (M-CMTC) syndrome, mesencephalic arteriovenous malformation (AVM), Langerhans cell histiocystosis. PRACTICAL RECOMMENDATIONS: It is important to take the age of the patient and the imaging pattern into account and to exclude tumors when reporting MR images of children with hydrocephalus.

[Non-invasive estimation of intracranial pressure : MR-based evaluation in children with hydrocephalus]. / Nichtinvasive Bestimmung des intrakraniellen Drucks : MR-basierte Untersuchung bei Kindern mit Hydrozephalus.

CLINICAL/METHODICAL ISSUE: The intracranial pressure (ICP) is a crucially important parameter for diagnostic and therapeutic decision-making in patients with hydrocephalus. STANDARD RADIOLOGICAL METHODS: So far there is no standard method to non-invasively assess the ICP. Various approaches to obtain the ICP semi-invasively or non-invasively are discussed and the clinical application of a magnetic resonance imaging (MRI)-based method to estimate ICP (MR-ICP) is demonstrated in a group of pediatric patients with hydrocephalus. METHODICAL INNOVATIONS: Arterial inflow, venous drainage and craniospinal cerebrospinal fluid (CSF) flow were quantified using phase-contrast imaging to derive the MR-ICP. PERFORMANCE: A total of 15 patients with hydrocephalus (n=9 treated with shunt placement or ventriculostomy) underwent MRI on a 3 T scanner applying retrospectively-gated cine phase contrast sequences. Of the patients six had clinical symptoms indicating increased ICP (age 2.5-14.61 years, mean 7.4 years) and nine patients had no clinical signs of elevated ICP (age 2.1-15.9 years; mean 9.8 years; all treated with shunt or ventriculostomy). Median MR-ICP in symptomatic patients was 24.5 mmHg (25th percentile 20.4 mmHg; 75th percentile 44.6 mmHg). Median MR-ICP in patients without acute signs of increased ICP was 9.8 mmHg (25th percentile 8.6 mmHg; 75th percentile 11.4 mmHg). Group differences were significant (p < 0.001; Mann-Whitney U-test). ACHIEVEMENTS: The MR-ICP technique is a promising non-invasive tool for estimating ICP. PRACTICAL RECOMMENDATIONS: Further studies in larger patient cohorts are warranted to investigate its application in children with hydrocephalus.

[Amitriptyline-induced cardiac arrest : treatment with fat emulsion]. / Amitriptylinbedingter Herz-Kreislauf-Stillstand : Behandlung mit Lipidemulsion.

A case of successful resuscitation of a patient with severe amitriptyline intoxication is reported. The measured amitriptyline serum levels far exceeded those assumed to be lethal according to the literature. Resuscitation was successful with the administration of intravenous fat emulsion and the patient recovered without any neurological sequelae.

[Orbital and intracranial complications of acute sinusitis. Diagnostics and therapy in children and adolescents]. / Orbitale und intrakranielle Komplikationen akuter Sinusitiden. Diagnostik und Therapie bei Kindern und Jugendlichen.

Orbital and intracranial complications of acute sinusitis occur more frequently in the pediatric population compared to adults due to anatomic differences. Since the introduction of antibiotics the frequency of such complications has been dramatically reduced. Nevertheless, even in the era of modern antibiotics these complications continue to occur and it is therefore of utmost importance not only to know about these complications but also to include them in the differential diagnosis. Appropriate diagnosis mainly based on CT scanning or magnetic resonance tomography is the basis for a rapid and sufficient and if necessary interdisciplinary treatment. In this CME article the diagnostic and therapeutic interventions in four young patients suffering from orbital or intracranial complications due to acute sinusitis are described and discussed in the context of the current literature and a clinical algorithm is introduced.

Decompensated hydrocephalus causing syringomyelia and tetraparesis: a case report.

OBJECTIVE: Various causes for the development of syringomelia are discussed. The influence of hydrocephalus upon syringomyelia is rarely reported and its role remains unclear. MATERIAL AND METHODS: We report a young female patient with shunt dysfunction and consequent syrinx development after child delivery. RESULTS: The patient showed rapid clinical deterioration after delivery. Treatment was shunt revision and reconstitution of CSF flow in the posterior fossa. After surgery, the patient showed regressive syringomyelia going along with a quick and pronounced clinical improvement. CONCLUSION: Development of syringomyelia can be caused by CSF flow disorders and hydrocephalus and may be aggravated by increased intra-abdominal pressure.

Reversible dementia and corresponding CSF alterations due to intraspinal lumbosacral metastasis of a prostate carcinoma.

We report, for the first time, how intraspinal carcinoma metastasis can cause reversible dementia accompanied by distinct cerebrospinal fluid (CSF) alterations. A 73-year-old male patient who suffered from rapidly progressive dementia and gait disturbance showed marked abnormalities of CSF tau protein, amyloid beta(1-42), and prostate-specific antigen. A lumbosacral, intraspinal metastasis from a prostate carcinoma was found, and after microsurgical removal, CSF alterations normalized and the clinical symptoms regressed. This case illustrates how malignant tumors can disturb brain function via indirect mechanisms.

p53 mutations versus EGF receptor expression in giant cell glioblastomas.

Recent studies have shown that there are distinct genetic pathways leading to the most malignant astrocytic neoplasm, the glioblastoma. Primary (de novo) glioblastomas are characterized by amplification/overexpression of the EGF receptor (EGFR) and, less frequently, of the MDM2 gene. Another pathway, operative in the progression of low-grade or anaplastic astrocytomas to secondary glioblastomas, is characterized by the frequent occurrence of p53 mutations. In this study, we assessed p53 mutations and EGFR expression in the giant cell glioblastoma. This rare variant is characterized by unusually large, multinucleated giant cells, but tends to be more confined and has been reported to carry a somewhat more favorable prognosis. We analyzed biopsies from 16 patients (mean age at clinical manifestation, 40 years). DNA sequencing revealed that 12 of 16 (75%) giant cell glioblastomas contained a p53 mutation. In 7 patients with two or more surgical interventions, the p53 mutation was already detected in the first biopsy. Focal EGFR overexpression, including multinucleated giant cells, was observed immunohistochemically in 9 of 16 (56%) tumors. However, most tumor areas lacked immunoreactivity, indicating that EGFR overexpression does not play a significant role in the evolution of this glioblastoma variant. These results suggest that giant cell glioblastomas develop de novo with a short preoperative history (mean, 47 +/- 40 days), but contain genetic alterations similar to those observed in secondary glioblastomas.

PTEN (MMAC1) mutations are frequent in primary glioblastomas (de novo) but not in secondary glioblastomas.

Loss of heterozygosity (LOH) on chromosome 10 is the most frequent genetic alteration associated with the evolution of malignant astrocytic tumors and it may involve several loci. The tumor suppressor gene PTEN (MMAC1) on chromosome 10q23 is mutated in approximately 30% of glioblastomas (WHO Grade IV). In this study, we assessed the frequency of PTEN mutations in primary glioblastomas, which developed clinically de novo, and in secondary glioblastomas, which evolved from low-grade (WHO Grade II) or anaplastic astrocytomas (WHO Grade III). Nine of 28 (32%) primary glioblastomas contained a PTEN mutation and an additional case showed a homozygous PTEN deletion. This indicates that after overexpression/amplification of the EGF receptor, loss of PTEN function is the most common alteration in primary glioblastomas. In this series, 5 of 28 (18%) primary glioblastomas showed both a PTEN mutation and EGFR amplification. In contrast, only 1 of 25 (4%) secondary glioblastomas contained a PTEN mutation, and none of them showed a homozygous PTEN deletion. The secondary glioblastoma with a PTEN mutation developed from an anaplastic astrocytoma that already carried the mutation. The observation that secondary glioblastomas have a p53 mutation as a genetic hallmark but rarely contain a PTEN mutation supports the concept that primary and secondary glioblastomas develop differently on a genetic level.

Fatal ethibloc embolization of vertebrobasilar system following percutaneous injection into aneurysmal bone cyst of the second cervical vertebra.

A 4-year-old boy developed progressive neck pain and an expansile osteogenic lesion of C2; the diagnosis was an aneurysmal bone cyst. An image-guided biopsy with 3D CT planning was performed followed by Ethibloc injection into the aneurysmal bone cyst. Subsequent CT and MR images demonstrated embolization material in the vertebrobasilar system, and the patient died of brain stem and cerebellar infarction 23 hours after the intervention. The course of events and technical considerations are discussed.

Congruence and discrepancy of interictal and ictal EEG with MRI lesions in focal epilepsies.

OBJECTIVE: To compare the occurrence and localization of interictal epileptiform discharges (IEDs) and epileptic seizure patterns (ESPs) with the localization of MRI lesions. METHODS: We retrospectively analyzed the EEG and MRI data of a series of patients with focal epilepsies that had been studied from 1991 to 2009. RESULTS: In patients with temporal lesions, the localization of IEDs was most congruent (58.6% with IEDs exclusively over the lesional lobe and 29.7% with a majority of temporal IEDs). This differed (p < 0.001) from frontal lesions (27.5% with exclusively frontal IEDs, 24.6% with a majority of frontal IEDs). In parieto-occipital lobe lesions, only 12.1% had IEDs exclusively over the lesional lobe compared to 48.5% with no parieto-occipital IEDs at all. Patients with central lesions often lacked any IEDs (54.5%, p < 0.001). The occurrence and localization of ESPs also differed between the regions. They were most congruent in temporal lesions (63.5% of patient had ESPs only over the lesional lobe, 23.4% had the majority of ESPs over the lesional lobe), which differed from frontal and parieto-occipital lesions (37.7% and 30.3% of patients with ESPs only over the lesional lobe). Patients with central lesions had ESPs very frequently only outside the lesional lobe (63.6%). Surgery outcome did not differ between the regions. CONCLUSIONS: The occurrence and localization of interictal and ictal EEG findings differs vastly for lesions in different brain regions. These findings should be used to carefully weigh the results from EEG studies particularly in patients with extratemporal epilepsies considered for epilepsy surgery.

Expression of BARHL1 in medulloblastoma is associated with prolonged survival in mice and humans.

Medulloblastoma is the most common malignant brain tumor in childhood, and development of targeted therapies is highly desired. Although the molecular mechanisms of malignant transformation are not fully understood, it is known that medulloblastomas may arise from cerebellar granule neuron precursors. The homeodomain transcription factor Barhl1 is known to regulate migration and survival of granule cell precursors, but its functional role in medulloblastoma is unknown. We show here that the expression of BARHL1 is significantly upregulated during human cerebellar development and in human medulloblastoma samples as compared with the normal adult cerebellum. We also detected high levels of Barhl1 expression in medulloblastomas of Math1-cre:SmoM2 mice, a mouse model for Sonic hedgehog-associated medulloblastomas that we developed previously. To investigate Barhl1 function in vivo during tumor development, we generated Barhl1(-/-)Math1-cre:SmoM2 mice. Interestingly, tumors that developed in these mice displayed increased mitotic activity and decreased neuronal differentiation. Moreover, survival of these mice was significantly decreased. Similarly, low expression of BARHL1 in human medulloblastoma cases was associated with a less favorable prognosis for patients. These results suggest that the expression of Barhl1 decelerates tumor growth both in human and in murine medulloblastomas and should be further investigated with respect to potential implications for individualized therapeutic strategies.

Long-term isoflurane therapy for refractory bronchospasm associated with herpes simplex pneumonia in a heart transplant patient.

A 47-year-old man with a history of heart transplant was admitted after severe traumatic brain injury and seizures. During mechanical ventilation, the patient developed bronchospasm that severely compromised respiratory function that led to cardiac arrest. After resuscitation, application of isoflurane through the Anaesthetic Conserving Device (AnaConDa) in the ICU successfully treated bronchospasm, provided adequate sedation, and enabled appropriate ventilation and diagnostic bronchoscopy. A subsequent bronchoalveolar lavage revealed a high amount of Herpes simplex DNA. Herpes simplex pneumonia was diagnosed and treated with acyclovir. Isoflurane treatment was applied for twelve days total without side effects on renal and cerebral function. The patient recovered quickly after the termination of sedation. At discharge, he was fully awake without focal neurological deficiency and his long-term outcome was excellent. This case demonstrates that isoflurane is a treatment option in life-threatening cases of bronchospasm and a safe option for long-term sedation.

Interstitial iodine-125 radiosurgery alone or in combination with microsurgery for pediatric patients with eloquently located low-grade glioma: a pilot study.

PURPOSE: The optimal therapeutic management of children with World Health Organization grade I and II gliomas not accessible to complete resection is poorly defined. Radical surgical resection is the first-line treatment for large hemispheric tumors, whereas interstitial iodine-125 radiosurgery (IRS) might be an attractive treatment concept for selected patients with small (tumor diameter in the range of 4 cm) and circumscribed tumors in any location of the brain. Precise high-dose application, maximal sparing of surrounding normal tissue, and the absence of long-term complications have been reported to be the hallmark of IRS. Therefore, the therapeutic impact and the risk of IRS alone or in combination with microsurgery (in case of larger tumor volumes) were prospectively examined. METHODS: Seven boys and four girls were included (mean age, 6.8 years; range, 11 months to 16 years). IRS (after stereotactic biopsy) was considered to be indicated for circumscribed tumors with a diameter in the range of 4 cm (four cases). For larger tumors, a combined microsurgical/radiosurgical approach was preferred (seven patients). Temporary iodine-125 seeds were used exclusively (tumor dose calculated to the boundary, 54 Gy; dose rate, 10 cGy/h). Tumor location was hypothalamic/suprasellar in four, lobar in three, deep (thalamus and pineal gland) in two, and within the brain stem in two children. Treatment effects of IRS were estimated according to the MacDonald criteria. RESULTS: A complete response after IRS was seen in four patients, and a partial response was seen in seven patients (median follow-up, 31.5 months). There was no perioperative morbidity after microsurgery and/or IRS, and no radiogenic complications occurred during the follow-up period. Five patients experienced an improvement in their deficits, and no deterioration in neurological/endocrine function was seen in any of the patients at the time of last follow-up evaluation. CONCLUSION: IRS alone or in combination with microsurgery (in the case of larger tumors) is a safe, effective, and minimally invasive treatment strategy for eloquently located pediatric low-grade gliomas and deserves further prospective evaluation.