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.

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.

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.

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.

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.

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.

[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.

A new type of leukoencephalopathy with metaphyseal chondrodysplasia maps to Xq25-q27.

BACKGROUND: The authors report a three-generation family with four male patients presenting with a novel type of X-chromosomal leukoencephalopathy associated with skeletal abnormalities. METHODS: The index patient and his brother reached their early motor milestones in due time and had normal language development. Between the ages of 2 and 3 years, first signs of spastic paraplegia were noticed. Furthermore, the patients developed tremor, ataxia, optic atrophy, and spastic tetraparesis. Both boys had broad wrists and knees without significant contractures. A maternal uncle and a granduncle had the same disease. RESULTS: Leukoencephalopathy (MRI, MRS) and metaphyseal chondrodysplasia (X-ray, MRI) were diagnosed. MRS showed a reduction of choline-containing compounds in the white matter. An autopsy on one of the patients, who died at age 37 years, revealed an orthochromatic type of leukoencephalopathy. In bone and cartilage tissue, unspecific signs of a mild chondrodysplasia were found. At the PLP gene locus an obligate recombination was observed, which excludes the Pelizaeus-Merzbacher locus on Xq21-22. However, affected males share a fragment of the long arm of chromosome X. CONCLUSION: The authors report a new type of leukoencephalopathy associated with metaphyseal chondrodysplasia located on Xq25-q27.

Cystic leukoencephalopathy without megalencephaly: a distinct disease entity in 15 children.

OBJECTIVE: To describe a distinctive syndrome of nonprogressive encephalopathy, normo- or microcephaly, and early onset of severe psychomotor impairment in 15 white patients, including two siblings and two first cousins. METHODS AND RESULTS: MRI revealed bilateral cysts in the anterior part of the temporal lobe and white matter abnormalities with pericystic abnormal myelination and symmetric lesions in frontal and occipital periventricular regions. None of the usual inborn errors of metabolism/infectious diseases associated with leukoencephalopathy and bilateral anterior temporal lobe cysts were detected. CONCLUSIONS: These patients' clinical signs and cranial MRI abnormalities are strikingly similar and may represent a distinctive disease with autosomal-recessive inheritance: cystic leukoencephalopathy without megalencephaly.

Neuroradiological findings in glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency).

This article summarizes the magnetic resonance imaging features of glutaric aciduria type I (GA I) based on the cases presented at the 3rd International Workshop on Glutaryl-CoA Dehydrogenase Deficiency together with a review of previously reported neuroimaging characteristics of GA I. Previous reports have focused on characteristic findings, such as basal ganglia injury and frontotemporal atrophy or hypoplasia, subdural effusions and white-matter disease. Most of these findings have been demonstrated in symptomatic children, i.e. after manifestation of acute encephalopathic crises. In contrast, prospective investigations in presymptomatically diagnosed children are rare. Since more recent investigations have highlighted CNS changes in patients without encephalopathic crises, systematic prospective investigations of neuroradiological findings in this disease are indispensable for a better understanding of this disease. Based on these findings a suggestion for a MRI protocol is presented, supporting a standardized evaluation of patients with GA I.

Infantile cobalamin deficiency with cerebral lactate accumulation and sustained choline depletion.

A remarkable, intermittent sudden-onset vigilance and movement disorder in an exclusively breast-fed infant is reported, which was caused by cobalamin depletion due to maternal vitamin B12 malabsorption. The lack of cobalamin caused a severe encephalopathy in the infant, whose brain displayed a striking loss of volume and a delay of myelination. Proton magnetic resonance spectroscopy revealed an accumulation of lactate in the gray and white matter of the brain and a sustained depletion of choline-containing compounds in the white matter, reflecting a reversible disturbance of oxidative energy metabolism in brain cells and a long-lasting hypomyelination disorder. The clinical picture in conjunction with MRI and spectroscopic data of this case study yields more insight into the functions of cobalamin in the cerebral metabolism.

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.

Angiographic follow-up of vertebrobasilar artery aneurysms treated with detachable coils.

Endovascular treatment of ruptured vertebrobasilar artery aneurysms with Gugliemi detachable coils (GDC) has become an alternative to surgery. Mid-term angiographic follow-up can now be reported. Of 111 vertebrobasilar aneurysms in 110 patients we treated with GDC since 1992, 53 underwent angiography within 1 year and 59 after more than 18 months. We did not achieve complete occlusion on initial treatment of 23 aneurysms (21%). Complications were observed in 19 patients (17%), leading to permanent clinical disability in eight. Enlargement of the neck or reopening was seen in 12 (23%) of 53 aneurysms followed by angiography within 12 months. Documented recanalisation was treated in four (8%). Angiography was performed after 18-78 months in 59 patients, of whom nine, including three with initially incomplete occlusions, were retreated with GDC. Within the entire second observation period, three (5%) of the 59 patients had a further haemorrhage and were retreated with GDC. Rebleeding proved to be the only factor influencing the clinical outcome of retreated patients.

Operative or endovascular treatment of ruptured intracranial vertebral artery aneurysms?

Our purpose was to evaluate the surgical and endovascular treatment outcomes of ruptured intracranial vertebral artery aneurysms (RIVAA). The outcomes of 44 patients with RIVAA treated between 1983 and 1998 surgically (26), endovascularly (20) or both (2) were evaluated. The aneurysms were clipped in 24 patients, and clipped and wrapped in two. We treated 20 by the endovascular approach, 12 with Guglielmi detachable coils (GDC), and eight by parent-vessel occlusion using detachable balloons. Three patients had endovascular treatment after a failed or inadequate surgical attempt. Posttreatment follow-up was 17-183 months (mean 101 months) for surgically treated patients. For the GDC-treated group angiographic follow-up was carried at 8-49 months (mean 19 months). The condition of seven (27 %) of the surgically treated patients worsened due to procedure-related complications, compared with 10% in the endovascular treatment group. Of the patients initially presenting with Hunt and Hess grade IV or V, three of five (60%) died who were treated surgically and two of eight (25%) who were treated endovascularly. A good outcome was achieved in 17 surgically treated patients (85% of the survivors) and in 16 of the endovascular group (89% of the survivors). This present "same-site" report on treatment of a specific abnormality, RIVAA, treated surgically or by an endovascular approach indicates that especially in poorer Hunt and Hess grade patients, the latter may offer a clinical outcome as good as that of surgery, although long-term efficacy of GDC treatment is still to be determined.

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.

[Treatment of hemophagocytic lymphohistiocytosis, HLH, with bone marrow transplantation]. / Behandlung der Hämophagozytischen Lymphohistiozytose, HLH, mit Knochenmarktransplantation.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease of infancy and young childhood. The clinical presentation includes recurrent unexplained fever with hepatosplenomegaly. Cytopenia, hypofibrinogenemia and/or hypertriglyceridemia and hemophagocytosis in bone marrow, spleen and lymphnode confirm the diagnosis. Hemophagocytosis may not be present at the beginning. In these cases, diagnosis is facilitated by a positive family history, a relapsing course of the disease, the frequent involvement of the central nervous system and positive findings on immunological work-up. Treatment by chemotherapy and immunosuppressants can achieve sustained remissions in most patients and reinduction of remission after relapse is possible. Most children however, eventually die from progressive disease. At present, allogeneic bone marrow transplantation is the only curative therapeutic option. Between August 1992 and May 1997 eleven consecutive patients with HLH received bone marrow from unrelated (n = 7) or matched sibling donors (n = 4). The conditioning regimen consisted of busulfan, VP-16 and cyclophosphamide. Patients engrafted after a median time of 16 days (13-43). Only one patient developed grade III acute GVHD, another patient, grade II acute GVHD. Although regimen-related toxicity was extensive, all patients have survived without signs of HLH after a median follow up of 20 months (8-63). One patient suffers from chronic GVHD, three patients reveal psychomotoric retardation and one patient has severe impairment with spastic tetraparesis, amaurosis and seizures. Our experience shows that HLH can be successfully treated by allogeneic BMT from unrelated donors.