Occurrence of occult CSF leaks during standard FESS procedures.

OBJECTIVE: To determine the incidence of occult cerebrospinal fluid leaks (CSF) after functional endoscopic sinus surgery (FESS) and to evaluate the diagnostic performance of beta2-transferrin in blood-contaminated conditions. STUDY DESIGN: Prospective cohort study. METHODS: An analysis of 57 intraoperative samples using hydrogel 6 beta2-transferrin assay after FESS was undertaken. In case of CSF positive samples and continuing rhinorrhea, reanalysis after more than 1 year was conducted. In-vivo analysis of a primary spontaneous CSF leak sample took place to verify difficulties in detecting beta2-transferrin in blood-contaminated settings. Own titrations were performed to evaluate detection limits of CSF by beta2-transferrin and beta-trace protein assays in these settings. RESULTS: An incidence of 13% for occult CSF leaks after FESS was found. In blood-contaminated conditions, routine beta2-transferrin assays showed low sensitivity. In over 1 year follow-up, all samples were negative for CSF and none of them developed clinical relevant CSF leaks or meningitis. CONCLUSION: Occult and clinically irrelevant CSF leaks do occur in a significant proportion of patients during and shortly after FESS. Intra- and postoperatively, routine beta2-transferrin assays show low sensitivity. They should not be used in these settings. The clinical course of patients with occult CSF leaks indicated possibility of an uneventful follow-up.

Hippocampal infarction: Identification of three new types.

BACKGROUND AND PURPOSE: Hippocampal infarction (HI) is common but yet still not comprehensively studied. In the present study, we aimed to identify novel HI patterns and to describe additional ischemic lesions outside the hippocampus to draw conclusions regarding the underlying vessel occlusion. METHODS: In 222 patients (mean age 69.9 (±13.6) years; 129 (58.1%) male, 93 (41.9%) female) with HI, diffusion-weighted images were analyzed with emphasis on HI patterns and associated ischemic lesions outside the hippocampus. HI were classified as type 1 (complete), 2 (lateral), 3 (dorsal), and 4 (circumscribed). Further possible HI patterns were defined and classified as type 5 (ventral), 6 (ventrolateral), and 7 (dorsolateral). RESULTS: Unilateral HI was found in 218 (98.2%) patients. In these, type 5 and 6 were identified in 5 (2.3%) patients, and type 7 in 8 (3.7%) patients respectively. Type 1 was found in 62 (28.4%), 2 in 53 (24.3%), 3 in 57 (26.1%), and 4 in 28 (12.8%) patients. Further ischemic lesions were found in the territory of the anterior cerebral artery (3.6%), middle cerebral artery (14.9%), anterior choroidal artery (AChA) (7.2%), posterior cerebral artery (89.6%), and in the brainstem (6.3%) and cerebellum (20.3%). Type 5 and 6 were significantly associated with acute ischemic lesions in the AChA territory (6/10 (60%) vs. 11/200 (5.5%), P<0.001). CONCLUSIONS: We identified three novel HI types. Probably, type 5 and 6 can be attributed to occlusion of the AChA. Overall, these HI types are rare, possibly due to a better collateralization in the case of AChA occlusion.

Frequency and temporal profile of recanalization after cerebral vein and sinus thrombosis.

BACKGROUND AND PURPOSE: The temporal course of recanalization and its association with clinical outcome were analysed in our patients with cerebral sinus and/or venous thrombosis (CSVT) and follow-up magnetic resonance imaging (MRI). METHODS: Between January 1998 and September 2014 all patients from our institutions with CSVT were systematically analysed. Baseline data, treatment characteristics and follow-up MRI were retrospectively recorded. The status of recanalization was assessed as complete (CRec), partial (PRec) or failed recanalization. Clinical follow-up was measured with the modified Rankin Scale. Excellent outcome was defined as modified Rankin Scale 0-1. RESULTS: Ninety-nine patients were identified; 97% of these patients were treated with oral anticoagulation (OAC) and the median (min-max) time of OAC was 7 months (1-84). CRec was achieved in 57.6% (57/99), PRec in 29.3% (29/99) and only 13 (13.1%) patients did not recanalize. The median (min-max) time to PRec was 4 months (0.25-14) and to CRec 6 months (2-34). Median time to last clinical follow-up was 8 months (1-88); 91.8% (89/99) had an excellent outcome at last clinical follow-up and only 2.1% (2/99) died. Only thrombosis of the superior sagittal sinus was independently associated with successful recanalization (odds ratio 16, 95% confidence interval 2-138). No severe haemorrhagic complications and no recurrence of CSVT occurred within clinical follow-up. No association of outcome and recanalization status was found. CONCLUSIONS: The recanalization rate of CSVT under OAC was high and the median time to CRec was 6 months. Thrombosis of the superior sagittal sinus is a positive predictor of recanalization. Outcome in this cohort was excellent but no significant association of outcome and recanalization status was found.

[Hemiparesis in acute lymphoblastic leukemia]. / Hemiparese bei akuter lymphoblastischer Leukämie.

The case of an adolescent female patient with acute lymphoblastic leukemia and stroke-like hemiparesis demonstrates a typical manifestation of methotrexate-induced acute encephalopathy. This rare entity occurs both in children and adults and can result from intrathecal as well as high dose intravenous administration of methotrexate. Diagnosis can confidently be made using cerebral MRI including diffusion-weighted imaging (DWI), so that patients can be informed about the favorable prognosis.

Guideline for the diagnosis and management of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I).

Glutaryl-CoA dehydrogenase (GCDH) deficiency is an autosomal recessive disease with an estimated overall prevalence of 1 in 100 000 newborns. Biochemically, the disease is characterized by accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine, which can be detected by gas chromatography-mass spectrometry of organic acids or tandem mass spectrometry of acylcarnitines. Clinically, the disease course is usually determined by acute encephalopathic crises precipitated by infectious diseases, immunizations, and surgery during infancy or childhood. The characteristic neurological sequel is acute striatal injury and, subsequently, dystonia. During the last three decades attempts have been made to establish and optimize therapy for GCDH deficiency. Maintenance treatment consisting of a diet combined with oral supplementation of L: -carnitine, and an intensified emergency treatment during acute episodes of intercurrent illness have been applied to the majority of patients. This treatment strategy has significantly reduced the frequency of acute encephalopathic crises in early-diagnosed patients. Therefore, GCDH deficiency is now considered to be a treatable condition. However, significant differences exist in the diagnostic procedure and management of affected patients so that there is a wide variation of the outcome, in particular of pre-symptomatically diagnosed patients. At this time of rapid expansion of neonatal screening for GCDH deficiency, the major aim of this guideline is to re-assess the common practice and to formulate recommendations for diagnosis and management of GCDH deficiency based on the best available evidence.

Pharmacokinetic Modeling of Intra-arterial Nimodipine Therapy for Subarachnoid Hemorrhage-Related Cerebral Vasospasm.

PURPOSE: Intra-arterial (IA) administration of nimodipine has been shown to be an effective treatment for subarachnoid hemorrhage-related cerebral vasospasm. The concentrations achieved in cerebral arteries during this procedure, though, are unknown. Therefore, there are no clinical studies investigating dose-dependent effects of nimodipine. We aimed at providing a pharmacokinetic model for IA nimodipine therapy for this purpose. METHODS: A two-compartment pharmacokinetic model for intravenous nimodipine therapy was modified and used to assess cerebral arterial nimodipine concentration during IA nimodipine infusion into the internal carotid artery (ICA). RESULTS: According to our simulations, continuous IA nimodipine infusion at 2 mg/h and 1 mg/h resulted in steady-state cerebral arterial concentrations of about 200 ng/ml and 100 ng/ml assuming an ICA blood flow of 200 ml/min and a clearance of 70 l/h. About 85 % of the maximal concentration is achieved within the first minute of IA infusion independent on the infusion dose. Within the range of physiological and pharmacokinetic data available in the literature, ICA blood flow has more impact on cerebral arterial concentration than nimodipine clearance. CONCLUSION: The presented pharmacokinetic model is suitable for estimations of cerebral arterial nimodipine concentration during IA infusion. It may, for instance, assist in dose-dependent analyses of angiographic results.

Isolated punctuate hippocampal infarction and transient global amnesia are indistinguishable by means of MRI.

Background Small punctuate lesions in the hippocampus on diffusion-weighted images are a typical finding in transient global amnesia. Consequently, it has been suggested that diffusion-weighted images findings might corroborate the diagnosis of transient global amnesia. However, isolated punctuate hippocampal infarction might be a differential diagnosis of transient global amnesia. Aim Evaluation of isolated punctuate hippocampal infarction frequency and comparison of its clinical presentation and MRI findings to transient global amnesia. Methods From an MRI database, we identified 10 patients with isolated punctuate hippocampal infarction and compared these to 12 patients with transient global amnesia with diffusion-weighted images lesion with regard to clinical symptoms and MRI findings. Results Disorientation and memory deficits were more common in transient global amnesia patients, whereas dysphasia/aphasia and vertigo were more common in hippocampal infarction patients. MRI findings in isolated punctuate hippocampal infarction and transient global amnesia did not differ significantly, neither regarding the affected hemisphere, lesion distribution, size, nor relative ADC values. Conclusions Differentiation of isolated punctuate hippocampal infarction and transient global amnesia based on neuroimaging findings is not possible. Thus, in the case of isolated punctuate hippocampal diffusion-weighted images lesions the final diagnosis of hippocampal infarction or transient global amnesia should be based on the clinical presentation.

Ornithine decarboxylase activity in relation to DNA synthesis in mouse interfollicular epidermis and hair follicles.

The relationship between ornithine decarboxylase (L-ornithine carboxylyase, EC 4.1.1.17) activity and DNA synthetic activity was studied in mouse epidermis. Interfollicular epidermis and hair follicles were investigated separately. It was found that, in hair follicles, the variations of DNA replicative activity, which are reflected in the cyclic growth of hair, are paralleled by corresponding changes in ornithine decarboxylase activity. In both interfollicular epidermis and hair follicles, stimulation of DNA synthetic activity by plucking of hair induced a rapid and marked increase in ornithine decarboxylase activity. The relationship of steady-state and induced ornithine decarboxylase activity to DNA synthetic activity was compared in hair follicles and interfollicular epidermis. A correlation between the activity of this enzyme and DNA replication was found thereby in each of these tissues.

Association of morphological characteristics with precocious puberty and/or gelastic seizures in hypothalamic hamartoma.

The pathogenesis of central precocious puberty (PP) and/or gelastic seizures due to a hypothalamic hamartoma (HH) is still under debate. We evaluated the association of clinical symptoms with morphology and localization of the HH in 34 patients. The majority (86.4%) of HHs in patients with isolated PP (n = 22; 68.2% females) revealed a parahypothalamic position without affecting the third ventricle (91%). Half of them were pedunculated, and 40.9% showed a diameter less than 10 mm. In contrast, 11 of 12 patients with seizures, eight of whom were male, presented with a sessile intrahypothalamic hamartoma, 10 of which distorted the third ventricle. Logistic regression analysis revealed an increased relative risk (RR) for epilepsy in males (RR, 4.3; 95% confidence interval, 0.96-19). However, combination of the risk factor gender with intrahypothalamic position (RR, 19; 1.3-285) and distortion of the third ventricle (RR, 10; 0.6-164) reduced the risk associated with male gender to 1.1. The position of a HH and involvement of the third ventricle are likely to be more predictive for clinical characteristics than size and shape. Male gender was associated with an intrahypothalamic HH and epilepsy, suggesting a sexually dimorphic developmental pattern of this heterotopic mass.

Congenital clivus chordoma.

The authors report a case of a congenital clivus chordoma that caused cranial nerve palsy and hydrocephalus within a few days after birth. The tumor was well demonstrated by sonography, CT, and MR; the preoperative diagnosis was histologically confirmed after subtotal resection.

Preoperative embolization of intracranial meningiomas with a fibrin glue preparation.

BACKGROUND AND PURPOSE: Preoperative embolization expands the spectrum of meningioma that can be operated on safely. Our goal was to achieve the distalmost loading of the vascular bed and confluent tumor necrosis with a fibrin glue preparation in the preoperative embolization of meningiomas. METHODS: Between 1992 and 1997, 80 patients with a meningioma had diagnostic angiography with a standard transfemoral Seldinger technique, performed with a 6F guiding catheter and digital subtraction angiography. Preoperative embolization was carried out in the same session with an additional microcatheter system. Fibrin glue was the only component used. In all cases, CT was performed immediately after embolization; in nine patients, MR imaging was also performed. RESULTS: Angiography verified the elimination of tumor blush in all patients. The high-density areas seen on postembolization CT scans, caused by the fibrin glue dispersed in the embolized supply area, were found to be necrotic at surgery and were easily removed by suction. Two (2.5%) of the 80 patients had complications associated with embolization that resulted in neurologic deficits. CONCLUSION: The most effective preoperative embolization of tumors requires a distalmost loading of the vascular bed. Fibrin glue, which is easy to use and safe to handle, causes confluent tumor necrosis within the injected vascular territory.

Slow progression of juvenile metachromatic leukodystrophy 6 years after bone marrow transplantation.

Metachromatic leukodystrophy refers to a group of genetic neurologic diseases caused by deficiencies of the enzyme arylsulfatase A and the resulting accumulation of sulfatides in white matter. Bone marrow transplantation has been advocated as a treatment in an attempt to correct the enzyme deficiency. Such a transplant was performed in 1991 in a 16-year-old girl with a form of late juvenile metachromatic leukodystrophy caused by a homozygous P426L mutation in the arylsulfatase A gene. Engraftment was prompt and resulted in constant enzymatic normalization of circulating lymphocytes. The elevated urinary excretion of sulfatides remained unaffected. Clinical findings up until transplantation consisted of gait disturbances, impairment of cognitive functioning, and deterioration in school performance over several years. During a 6-year follow-up period, the patient's condition was subject to major fluctuations but, on the whole, findings showed slow neurologic and neurophysiologic deterioration. The clinical course observed after bone marrow transplantation probably more or less reflects the natural course expected in this form of late-onset metachromatic leukodystrophy.

Magnetic resonance imaging flow quantification of non-occlusive excimer laser-assisted EC-IC high-flow bypass in the treatment of complex intracranial aneurysms.

The patency of a bypass plays an important role in the postoperative recovery of patients especially when dealing with complicated intracranial aneurysms. In this study two-dimensional phase contrast magnetic resonance angiography (PC-MRA) was used to measure cerebral blood flow in 23 patients before extracranial-intracranial high-flow bypass surgery using the excimer laser-assisted non-occlusive anastomosis (ELANA) technique and in 15 patients following surgery. The results showed that PC-MRA is a suitable technique for assessing bypass patency and that with the ELANA technique the bypass has the capability of compensating the blood flow of an occluded internal carotid artery (ACI) in cases of complex aneurysms.

Dynamic magnetic resonance imaging of the cervical spine with high-resolution 3-dimensional T2-imaging.

PURPOSE: Imaging of the cervical spine in functional positions has so far been limited to conventional X-ray examinations or the scarcely available open magnetic resonance imaging (MRI). An MRI compatible positioning device allows MRI examinations in various positions and even in motion. In combination with high-resolution T2-weighted MRI it allows detailed functional imaging of the cervical spine and nerve roots. To evaluate the utility of this method a population of patients from a clinical study was examined 5 years after anterior cervical discectomy and fusion (ACDF). METHODS: A total of 32 patients (median age 51.5 years, 15 female, 17 male) were examined after a median interval of 64.3 months from ACDF including 16 patients with a titanium cage and 16 with autologous bone graft. The prototype of an MR compatible positioning device (NeuroSwing) was used for MRI of the cervical spine in functional positions on a 1.5 T MRI unit (Siemens Avanto). A real-time true fast imaging with steady-state precession (FISP) sequence [6 mm, TR 704, TE 1.3 ms, matrix 256 x 207, field of view (FoV) 22 cm] was used for monitoring of flexion up to 45° and extension up to 40° or until patient discomfort. A sagittal T2 sampling perfection with application optimized contrast using different flip angle evolution sequence (SPACE sequence, 0.9 mm isotropic voxels, TR 1770, TE 186 ms, matrix 320 x 318, FoV 28 cm) and an axial true FISP sequence (3 mm slices, TR 194, TE 1.9 ms, matrix 256 x 256, FoV 22 cm) were used for imaging in the end positions. RESULTS: Using the motorized positioning device and a real-time true FISP sequence, imaging of the cervical spine in flexion and extension motion was possible in a quality suitable to observe changes in the alignment of vertebral bodies, the width of the spinal canal and the spinal cord itself. The 3D T2-weighted SPACE sequence yielded high quality and resolution images in the maximum flexion and extension positions. Compared to primary axial T2 true FISP slices, axial reconstructions of the T2 SPACE sequence were found to be clearly less affected by metal artifacts with the additional benefit of multiplanar and transforaminal reconstructions. CONCLUSIONS: The combination of a mechanical positioning device and a high-resolution 3D T2-weighted sequence (SPACE) on a conventional 1.5 T MRI allows kinematic imaging of the cervical spine as well as high-resolution imaging in the end positions, even in the presence of metal implants. In this proof of concept study a good visualization of narrowing of the spinal canal in functional positions could be achieved, showing the potential of MRI in functional positions for clinical and research applications.