TSPO PET imaging of natalizumab-associated progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a severe infection of the CNS caused by the polyomavirus JC that can occur in multiple sclerosis patients treated with natalizumab. Clinical management of patients with natalizumab-associated PML is challenging not least because current imaging tools for the early detection, longitudinal monitoring and differential diagnosis of PML lesions are limited. Here we evaluate whether translocator protein (TSPO) PET imaging can be applied to monitor the inflammatory activity of PML lesions over time and differentiate them from multiple sclerosis lesions. For this monocentre pilot study we followed eight patients with natalizumab-associated PML with PET imaging using the TSPO radioligand 18F-GE-180 combined with frequent 3 T MRI. In addition we compared TSPO PET signals in PML lesions with the signal pattern of multiple sclerosis lesions from 17 independent multiple sclerosis patients. We evaluated the standardized uptake value ratio as well as the morphometry of the TSPO uptake for putative PML and multiple sclerosis lesions areas compared to a radiologically unaffected pseudo-reference region in the cerebrum. Furthermore, TSPO expression in situ was immunohistochemically verified by determining the density and cellular identity of TSPO-expressing cells in brain sections from four patients with early natalizumab-associated PML as well as five patients with other forms of PML and six patients with inflammatory demyelinating CNS lesions (clinically isolated syndrome/multiple sclerosis). Histological analysis revealed a reticular accumulation of TSPO expressing phagocytes in PML lesions, while such phagocytes showed a more homogeneous distribution in putative multiple sclerosis lesions. TSPO PET imaging showed an enhanced tracer uptake in natalizumab-associated PML lesions that was present from the early to the chronic stages (up to 52 months after PML diagnosis). While gadolinium enhancement on MRI rapidly declined to baseline levels, TSPO tracer uptake followed a slow one phase decay curve. A TSPO-based 3D diagnostic matrix taking into account the uptake levels as well as the shape and texture of the TSPO signal differentiated >96% of PML and multiple sclerosis lesions. Indeed, treatment with rituximab after natalizumab-associated PML in three patients did not affect tracer uptake in the assigned PML lesions but reverted tracer uptake to baseline in the assigned active multiple sclerosis lesions. Taken together our study suggests that TSPO PET imaging can reveal CNS inflammation in natalizumab-associated PML. TSPO PET may facilitate longitudinal monitoring of disease activity and help to distinguish recurrent multiple sclerosis activity from PML progression.

Uncrossed corticospinal tract in health and genetic disorders: Review, case report, and clinical implications.

BACKGROUND AND PURPOSE: Crossing pathologies of the corticospinal tract (CST) are rare and often associated with genetic disorders. However, they can be present in healthy humans and lead to ipsilateral motor deficits when a lesion to motor areas occurs. Here, we review historical and current literature of CST crossing pathologies and present a rare case of asymmetric crossing of the CST. METHODS: Description of the case and systematic review of the literature were based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed database was searched for peer-reviewed articles in English since 1950. All articles on ipsilateral stroke, uncrossed CST, and associated neurologic disorders were screened. Furthermore, a literature review between the years 1850 and 1980 including articles in other languages, books, opinions, and case studies was conducted. RESULTS: Only a few descriptions of CST crossing pathologies exist in healthy humans, whereas they seem to be more common in genetic disorders such as horizontal gaze palsy with progressive scoliosis or congenital mirror movements. Our patient presented with aphasia and left-sided hemiparesis. Computed tomographic (CT) scan revealed a perfusion deficit in the left middle cerebral artery territory, which was confirmed by diffusion-weighted magnetic resonance imaging (MRI), so that thrombolysis was administered. Diffusion tensor imaging with fibre tracking revealed an asymmetric CST crossing. CONCLUSIONS: The knowledge of CST crossing pathologies is essential if a motor deficit occurs ipsilateral to the lesion side. An ipsilateral deficit should not lead to exclusion or delay of therapeutic options in patients with suspected stroke. Here, a combined evaluation of CT perfusion imaging and MRI diffusion imaging may be of advantage.

Travel-associated neurological disease terminated in a postmortem diagnosed atypical HSV-1 encephalitis after high-dose steroid therapy - a case report.

BACKGROUND: Human encephalitis can originate from a variety of different aetiologies, of which infection is the most common one. The diagnostic work-up is specifically challenging in patients with travel history since a broader spectrum of unfamiliar additional infectious agents, e. g. tropical disease pathogens, needs to be considered. Here we present a case of encephalitis of unclear aetiology in a female traveller returning from Africa, who in addition developed an atypical herpes simplex virus (HSV) encephalitis in close temporal relation with high-dose steroid treatment. CASE PRESENTATION: A previously healthy 48-year-old female presented with confusion syndrome and impaired vigilance which had developed during a six-day trip to The Gambia. The condition rapidly worsened to a comatose state. Extensive search for infectious agents including a variety of tropical disease pathogens was unsuccessful. As encephalitic signs persisted despite of calculated antimicrobial and antiviral therapy, high-dose corticosteroids were applied intravenously based on the working diagnosis of an autoimmune encephalitis. The treatment did, however, not improve the patient's condition. Four days later, bihemispheric signal amplification in the insular and frontobasal cortex was observed on magnetic resonance imaging (MRI). The intracranial pressure rapidly increased and could not be controlled by conservative treatment. The patient died due to tonsillar herniation 21 days after onset of symptoms. Histological examination of postmortem brain tissue demonstrated a generalized lymphocytic meningoencephalitis. Immunohistochemical reactions against HSV-1/2 indicated an atypical manifestation of herpesviral encephalitis in brain tissue. Moreover, HSV-1 DNA was detected by a next-generation sequencing (NGS) metagenomics approach. Retrospective analysis of cerebrospinal fluid (CSF) and serum samples revealed HSV-1 DNA only in specimens one day ante mortem. CONCLUSIONS: This case shows that standard high-dose steroid therapy can contribute to or possibly even trigger fulminant cerebral HSV reactivation in a critically ill patient. Thus, even if extensive laboratory diagnostics including wide-ranging search for infectious pathogens has been performed before and remained without results, continuous re-evaluation of potential differential diagnoses especially regarding opportunistic infections or reactivation of latent infections is of utmost importance, particularly if new symptoms occur.

Vestibular paroxysmia: clinical characteristics and long-term course.

In 2016, the Bárány Society defined new diagnostic criteria for the neurovascular compression syndrome of the eighth nerve, called "vestibular paroxysmia" (VP), differentiating between definite (dVP) and probable (pVP) forms. The aim of this study was (1) to describe clinical symptoms and laboratory findings in a well-diagnosed large patient cohort according to those criteria, and (2) to evaluate the long-term course over years in dVP. We identified 146 patients (73 dVP, 73 pVP) from our tertiary dizziness center registry. Data of structured history-taking, clinical neurological, neuro-ophthalmological/-otological examinations as well as MRI imaging were extracted for analyses. Overall, attack frequency ranged between 5 and 30 attacks per day; spinning vertigo was the most frequent type. In two-thirds of patients, attacks occurred spontaneously; in one-quarter, they were triggered by head movements. The majority (approximately 70%) reported no accompanying symptoms; in those with symptoms, mild unilateral cochlear symptoms prevailed. One-third of patients initially showed hyperventilation-induced nystagmus without specific direction, and a deviation of the subjective visual vertical between 3° and 6°. Complete loss of peripheral vestibular function was never evident. dVP and pVP significantly differed concerning the vertigo type, e.g., spinning vertigo was more frequent in dVP. Fortunately, three-quarters of dVP patients remained attack-free during follow-up (mean 4.8 years, standardized questionnaire), more than half of them even without any medication. Patients with ongoing attacks showed significantly higher attack frequency at baseline, but reported persistent frequency reduction. Overall, the long-term prognosis of VP appears favorable, not necessarily requiring ongoing treatment.

Semiquantitative 3T Brain Magnetic Resonance Imaging for Dynamic Visualization of the Glymphatic-Lymphatic Fluid Transport System in Humans: A Pilot Study.

OBJECTIVES: Recently, a novel clearing system for interstitial solutes of the brain was described as a perivascular pathway named the glymphatic system. Furthermore, lymphatic vessels were found in the meninges to drain interstitial fluids. It is hypothesized that interstitial solutes, such as amyloid ß, are firstly processed through the brain by the glymphatic system and secondly drained out of the brain by lymphatic vessels (glymphatic-lymphatic fluid transport system [GLS]). Since then, various neurological disorders, such as Alzheimer disease, have been associated with a dysfunction of the GLS. In the current study, we aimed to establish a clinical magnetic resonance imaging (MRI) study protocol for visualizing lymphatic vessels as part of the GLS in humans. More importantly, we aimed to describe the dynamic changes of a contrast agent in these lymphatic vessels over time. MATERIALS AND METHODS: Twenty volunteers with an unremarkable neurological/psychiatric history were included in this 3T MRI study. Serial MRI sequence blocks were performed at 3 predefined time points (TPs): TP 1, precontrast MRI before administration of a gadolinium-based contrast agent (GBCA); TP 2, immediately post-GBCA (early ce-MRI); and TP 3, 60 minutes post-GBCA (late ce-MRI). Each MRI block contained the following sequences obtained in the same order: whole-brain 3D T1-MPRAGE, whole-brain 3D T2-FLAIR, focused 2D T2-FLAIR, and whole-brain 3D T1-SPACE. Signal intensity (SI) in compartments of the GLS adjacent to the superior sagittal sinus, gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) was calculated by manually placed regions of interest. The time course of the signal intensities was examined by generalized linear mixed models. The data were adjusted for age, cognitive function (Montreal-Cognitive-Assessment test), and sleep quality (Pittsburgh Sleep Quality Index questionnaire). RESULTS: The GLS was best visualized in the 2D T2-FLAIR and 3D T1-SPACE sequences, enabling further SI measurement. In precontrast (TP 1), the SI within the GLS was significantly higher than in CSF and significantly lower than in GM and WM. In post-GBCA, a significant increase (TP 2) and decrease (TP 3), respectively, of the GLS SI values were noted (86.3 ± 25.2% increase and subsequent decrease by 25.4 ± 9% in the 3D T1-SPACE sequence). The SI values of CSF, GM, and WM did not change significantly between the 3 TPs. CONCLUSIONS: A clinical MRI study protocol was established for the visualization of lymphatic vessels as an important part of the GLS and therefore the brain's clearing mechanism of interstitial solutes. Furthermore, dynamic changes in the GLS were described over time, possibly reflecting the clearing function of the GLS. This might constitute the basis for evaluating the GLS function in manifold neurological pathologies in the future.

Incidence, clinical spectrum, and immunotherapy of non-ischemic cerebral enhancing lesions after endovascular therapy.

BACKGROUND: Symptomatic and asymptomatic delayed non-ischemic cerebral enhancing (NICE) lesions in magnetic resonance imaging (MRI) have been reported as a rare complication after endovascular therapy (EVT) in recent years with incidence rates between 0.05% and 0.9% in most studies. Information on long-term clinical course and immunotherapies is scarce or has not been reported in detail in the literature. Objective: Aims of our study were to assess the incidence of NICE lesions in patients after cerebral EVT over a period of more than 12 years, describe clinical and EVT characteristics, and immunotherapies applied. METHODS: A retrospective chart review of all patients treated by endovascular therapy for symptomatic or asymptomatic aneurysms at the University Hospital of Augsburg from May 1, 2008 to December 31, 2020 was performed. Patients were identified retrospectively and followed-up prospectively where appropriate. In addition, one case treated at another institution was included. RESULTS: Five out of 746 patients, 0.67%, developed NICE lesions after EVT, all with non-ruptured aneurysms and all symptomatic upon detection of NICE lesions by MRI. In total, the disease course of 6 female patients is reported. Symptoms occurred after a mean time of 15 days (±13.42, SD) after EVT with headache (6/6 patients), focal neurological signs (6/6 patients), epileptic seizures (2/6 patients) and cognitive deficits (3/6 patients). All 6 patients received glucocorticosteroids (GCS), 1/6 azathioprine (AZA), 4/6 mycophenolate mofetil (MMF), 1/6 methotrexate (MTX), 1/6 rituximab (RTX), 2/6 cyclophosphamide (CYC) and 3/6 tocilizumab (TCZ). A treatment response could be observed for GCS, TCZ and MMF (in two of four cases), RTX and AZA did not result in disease stabilization. CONCLUSIONS: Delayed NICE lesions are a rare complication after EVT, requiring immunotherapies in all patients reported here. Physicians should be aware of this disorder in case of new symptoms or contrast enhancing lesions after EVT.

Trigeminal neuralgia due to neurovascular compression: high-spatial-resolution diffusion-tensor imaging reveals microstructural neural changes.

PURPOSE: To preoperatively detect, by using diffusion-tensor imaging coregistered with anatomic magnetic resonance (MR) imaging, suspected microstructural tissue changes of the trigeminal nerves in patients with trigeminal neuralgia (TN) resulting from neurovascular compression. MATERIALS AND METHODS: The study was approved by the institutional review board, and written informed consent was obtained from all patients. Twenty patients (mean age, 51.3 years) with TN and evidence of neurovascular contact were examined with use of a 3.0-T MR unit combined with an eight-channel head coil before undergoing surgical decompression. A single-shot diffusion-tensor echo-planar sequence was used along 15 different diffusion directions, with a b value of 1000 sec/mm(2) and a section thickness of 2 mm. For anatomic correlation, 0.6-mm isotropic three-dimensional fast imaging employing steady-state images were acquired for coregistration with the functional diffusion-tensor maps. After region of interest placement, mean fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were calculated for each nerve by using the paired-sample two-tailed t test (with P < .005 indicating significance) and compared with surgical findings. RESULTS: FA was significantly lower (P = .004) on the trigeminal neuralgia-affected side (mean FA, 0.203) than on the contralateral side (mean FA, 0.239). ADCs were nearly identical between the normal and TN-affected nerve tissues. CONCLUSION: These findings suggest that diffusion-tensor imaging enables the identification and quantification of anisotropic changes between normal nerve tissue and TN-affected trigeminal nerves. Coregistration of anatomic three-dimensional fast imaging employing steady-state imaging and diffusion-tensor imaging facilitates excellent delineation of the cisternal segments of the trigeminal nerves.

LINS1-associated neurodevelopmental disorder: Family with novel mutation expands the phenotypic spectrum.

OBJECTIVE: Clinical, neuroimaging, and genetic characterization of 3 patients with LINS1-associated developmental regression, intellectual disability, dysmorphism, and further neurologic deficits. METHODS: Three affected brothers from a consanguineous family from Afghanistan, their 2 healthy siblings, and both parents were all assessed in the clinic. General and neurologic examination, expert dysmorphology examination, and 3T brain MRI were performed. Whole-exome sequencing was performed for the 3 affected brothers, followed by Sanger sequencing in all available family members. RESULTS: The index patient and his 2 affected brothers presented a complex neurologic syndrome with similar features but marked intrafamilial phenotypical variability, including varying degrees of cognitive impairment, speech impairment, dystonia, abnormal eye movements, and dysmorphic features. All 3 affected brothers are homozygous for a novel, pathogenic frameshift mutation in LINS1, c.1672_1679del, and p.Gly558Profs*22, whereas both parents and healthy siblings are heterozygous for the mutation. No major brain malformations were evident in 3T brain MRI of the affected brothers. CONCLUSION: This consanguineous family with a novel mutation expands the spectrum of LINS1-associated disorder to include developmental regression, oculomotor signs, and dystonia, previously not described in the published 9 cases of this rare disorder. The 3T-MRI data from our 3 patients and review of the neuroimaging data in the literature showed unspecific brain MRI changes. LINS1 protein is a known modulating factor of the Wnt signaling pathway, with important roles in organogenesis including of the cerebral cortex. More research is warranted to disentangle the underlying pathophysiologic mechanisms, leading to cognitive impairment and the complex phenotype of LINS1-associated disorder.

Stenotrophomonas maltophilia brain abscesses after implantation of motor cortex stimulator.

We describe the first case of a patient with brain abscesses caused by Stenotrophomonas maltophilia as a complication after motor cortex stimulator implantation. Brain abscesses pose a challenge in diagnosis and treatment, because microbiological diagnosis is not always achieved, antibiotic drugs may not penetrate well into the CNS and some bacteria have resistances to typical empirical antibiotic drugs. In this case diagnosis was only made after removal of the stimulator and a long term treatment with antibiotic drugs was necessary. As neurostimulation devices become more common, formerly rare bacteria may become a more common complication. Bacteria with biofilm properties and a problematic resistance spectrum like Stenotrophomonas maltophilia should be included in the differential diagnosis, because they will not respond to the typical empirical treatment.

Brain diffusion tensor imaging changes in cerebrotendinous xanthomatosis reversed with treatment.

Cerebrotendinous xanthomatosis (CTX, MIM 213700) is a rare autosomal recessive lipid storage disorder caused by CYP27A1 mutations. Treatment with chenodeoxycholic acid (CDCA) may slow the progression of the disease and reverse some symptoms in a proportion of patients. In a non-consanguineous Caucasian family, two siblings with CTX were evaluated before treatment and prospectively followed-up every 6 months after starting CDCA therapy, using systematic clinical examination, neuropsychological tests, laboratory tests, electroencephalography (EEG) and brain MRI, diffusion tensor imaging (DTI) and tractography. A 30-year-old patient and her 27-year-old brother were referred for progressive spastic paraparesis. Both had epilepsy, learning difficulties, chronic diarrhoea and juvenile-onset cataracts. CTX was diagnosed by increased cholestanol levels and compound heterozygosity for CYP27A1 mutations. Therapy with CDCA led to resolution of chronic diarrhoea, normalisation of serum cholestanol and EEG, and a progressive improvement in gait, cognition and seizure control. Before treatment, conventional brain MRI showed no CTX-related abnormalities for the proband and no cerebellar abnormalities for the brother, while DTI showed reduced fractional anisotropy (FA) and tract-density in the cerebellum and widespread cerebral reductions of FA in both patients, compared to a group of 35 healthy controls. Repeated DTI after starting therapy showed progressive increases of cerebellar tract density and of cerebral FA. In patients with CTX, therapy with CDCA may lead to significant clinical improvement, with normalisation of biochemical and electrophysiological biomarkers. DTI and tractography may detect changes when the conventional MRI is unremarkable and may provide potential neuroimaging biomarkers for monitoring treatment response in CTX, while the conventional MRI remains unchanged.

Extended studies of the striatal uptake of 99mTc-NC100697 in healthy volunteers.

UNLABELLED: This study evaluates a new formulation of a (99m)Tc-labeled tropane derivate, (99m)Tc-NC100697, in a human volunteer study. METHODS: Eighty healthy subjects (39 females, 41 males) underwent MRI and SPECT (injected dose [mean +/- SD], 10.6 +/- 1.4 MBq/kg). Forty subjects were investigated 30, 90, 180, 240, 360, and 480 min after injection, and another 40 subjects were imaged 240 min after injection. Specific striatal binding was assessed using 3 different approaches: 3-dimensional volumes of interest (VOIs) drawn on the coregistered MRI scans, manually placed predefined 2-dimensional regions of interest (ROIs), and observer-independent fully automated 3-dimensional VOI analyses based on coregistration of scans with a mean template of controls. Specific striatal dopamine transporter (DAT) binding was estimated for cohorts of ages of 21-30, 31-40, 41-50, 51-60, 61-70, and 71-80 y. The relationship between age and DAT binding was analyzed with linear, "broken-stick," exponential, and logarithmic regression. RESULTS: Serial SPECT scans revealed increasing values of specific DAT binding over time. Consideration of all important variables suggests an optimum imaging time at 4 h after injection. Average DAT binding for the total population was 1.1 +/- 0.2 (striatum), 1.3 +/- 0.2 (caudate), and 1.1 +/- 0.2 (putamen), with mean putamen-to-caudate ratios of 0.83 +/- 0.08 (manual 2-dimensional ROI method). A significant age dependency of striatal DAT binding, best described by a broken-stick (break-point age, 48 y) or logarithmic regression (both r = 0.76), with a lower decline observed in older than in younger subjects. Female subjects presented with slightly higher binding ratios than male subjects, more pronounced in pre- than in postmenopausal women. There was a high correlation between the 3 semiquantitative evaluations. CONCLUSION: The current study has demonstrated the effective use of (99m)Tc-NC100697 for estimating presynaptic striatal DAT binding. The comparison of different semiquantification methods showed that in clinical routine work, this tracer can be reliably evaluated without individual MRI data. Age and a slight sex dependency (especially in premenopausal women) of (99m)Tc-NC100697 binding should be taken into consideration. The data generated in this phase 1 study provides a basis for an age- and sex-matched normal database.

Cystic Craniopharyngiomas: Microsurgical or Stereotactic Treatment?

BACKGROUND: Prognosis and treatment of cystic craniopharyngiomas are poorly defined. OBJECTIVE: To analyze progression-free survival (PFS) and safety profile of cystic craniopharyngiomas undergoing resection or minimally invasive drainage procedures. We compared further outcome measurements for cystic and solid tumors undergoing resection to elucidate the impact of the initial tumor composition on both PFS and the toxicity profile. METHODS: All patients with craniopharyngiomas consecutively treated between 1999 and 2014 were included. A treatment decision in favor of microsurgery or stereotactic treatment was made interdisciplinarily. For stereotactic drainage, a catheter was implanted, allowing both permanent upstream (into ventricular spaces) and downstream (into prepontine cistern) drainage. Study endpoints were tumor progression, functional outcome, and treatment toxicity. Functional endocrinological and visual outcome analyses referred to data obtained preoperatively and 6 weeks after treatment. The Kaplan-Meier method was used for survival analysis. Prognostic factors were obtained from proportional hazard models. RESULTS: Seventy-nine patients were included. The distribution of clinical and tumor-related data was well balanced among patients with solid (n = 35) and cystic (n = 44) tumors and those undergoing microsurgical or stereotactic treatment. Cystic tumors had shorter PFS (5-year PFS: 53.6% vs 66.8%, P = .10) and needed significantly more therapeutic interventions, which was independent of the initial treatment mode. The endocrinological deterioration rate was high for both solid and cystic tumors after microsurgery (59.4% and 85.7%, respectively), whereas it was significantly lower for cystic tumors undergoing stereotactic treatment (23.1%, P < .001). CONCLUSION: Stereotactic bidirectional drainage of cystic craniopharyngiomas is effective and provides a better endocrinological outcome than conventional microsurgery.

Giant multilevel thoracic hemangioma with spinal cord compression in a patient with Klippel-Weber-Trenaunay syndrome: case report.

STUDY DESIGN: Case report and clinical discussion. OBJECTIVE: We intend to report a very rare case of a giant spinal hemangioma causing myelopathy. SUMMARY OF BACKGROUND DATA: Multilevel symptomatic spinal hemangiomas causing acute neurologic symptoms are rare disorders. We found only sporadic reports in English literature. METHODS: We describe a very rare case in which Klippel-Trenaunay-Weber syndrome is associated with a multisegmental vertebral hemangioma causing a rapidly progressing thoracic myelopathy. RESULTS: Because of the extension of the disease, surgical intervention was not feasible, the patient was treated by radiotherapy. The patient showed a complete regression of symptoms with stable condition after 3 months. CONCLUSIONS: In extensive spinal hemangiomas, radiotherapy may represent a safe treatment modality with rapid clinical improvement even in cases with spinal cord compression. This report contributes to a wide range of known vascular abnormalities in Klippel-Trenaunay-Weber syndrome and supports the need for a careful multisystemic evaluation of these patients.

Functional magnetic resonance imaging activations of cortical eye fields during saccades, smooth pursuit, and optokinetic nystagmus.

Saccades, smooth pursuit, and optokinetic nystagmus (OKN) are three basic eye movements in our ocular motor repertoire that enable us to explore the visual field. These eye movements are cortically controlled in different cortical eye fields, including the frontal eye fields (FEF) and parietal eye fields (PEF), as well as the motion-sensitive visual area MT+/V5. It is not known if this cortical control is organized in parallel cortico-cortical networks or in adjacent subregions of one system. Nor do we know where the specific eye fields are exactly located. Functional magnetic resonance imaging (fMRI) was used to investigate these open questions about the FEF, PEF, and MT+/V5. Activations of the cortical network of eye-movement control were found in the frontal, parietal, and occipital cortex. While the activation pattern for OKN was not a combination of the patterns for saccades and smooth pursuit, the results suggest that cortical control of OKN occurs in a network parallel to that of saccades and smooth pursuit. Furthermore, a division of the FEF and the PEF into two parts was confirmed for the three ocular motor tasks, as well as a division within each of the three paradigms. MT+/V5 showed two partitions only for saccades, but not for smooth pursuit or OKN.

FET PET for the evaluation of untreated gliomas: correlation of FET uptake and uptake kinetics with tumour grading.

PURPOSE: Treatment and prognosis of gliomas depend on their histological tumour grade. The aim of the study was to evaluate the potential of [(18)F]fluoroethyltyrosine (FET) PET for non-invasive tumour grading in untreated patients. METHODS: Dynamic FET PET studies were performed in 54 patients who, based on MRI, were estimated to have low grade (LG; n = 20), intermediate (WHO II-III; n = 4) or high grade (HG; n = 30) tumours. For standard evaluation, tumour SUV(max) and the ratio to background (SUV(max)/BG) were calculated (sum image: 20-40 min). For dynamic evaluation, mean SUV values within a 90% isocontour ROI (SUV90) and the SUV90/BG ratios were determined for each time frame to evaluate the course of FET uptake. Results were correlated with histopathological findings from PET-guided stereotactic biopsies. RESULTS: Histology revealed gliomas in all patients. Using the standard method a statistically significant difference (p = 0.001) was found between LG (n = 20; SUV(max)/BG: 2.16 +/- 0.98) and HG (n = 34; SUV(max)/BG: 3.29 +/- 1.06) gliomas (opt. threshold 2.58: SN71%/SP85%/area under ROC curve [AUC]:0.798), however, with a marked overlap between WHO II to IV tumours. Time activity curves showed slight increase in LG, whereas HG tumours presented with an early peak (10-20 min) followed by a decrease. Dynamic evaluation successfully separated LG from HG gliomas with higher diagnostic accuracy (SN94%/SP100%/AUC:0.967). CONCLUSIONS: Based on the ratio-based method, a statistically significant difference was found between LG and HG gliomas. Due to the interindividual variability, however, no reliable individual grading was possible. In contrast, dynamic evaluation allowed LG and HG gliomas to be differentiated with high diagnostic power and, thus, should supplement the conventional method.

Chronic high-frequency globus pallidus internus stimulation in different types of dystonia: a clinical, video, and MRI report of six patients presenting with segmental, cervical, and generalized dystonia.

The results of deep brain stimulation (DBS) of the globus pallidus internus (Gpi) in six patients with generalized, focal, and segmental dystonia are presented. Pre- and postoperative assessments are given for one patient with generalized inherited dystonia and for five patients with idiopathic segmental or cervical dystonia. Clinical symptoms were evaluated before and 3-12 months after surgery using the Burke-Fahn-Marsden (BFM) dystonia rating scale for primary torsion dystonia and the Tsui scale for cervical dystonia. The Short-Form Health Survey (SF-36) was completed by each patient to document preoperative and postoperative health status. Also, neurological status was documented by video before and during chronic stimulation. Magnetic resonance imaging studies were performed to show the anatomical localization of the electrode leads. Five patients showed a progressive improvement within 7 days. One patient with cervical dystonia and Meige's syndrome showed no improvement for 3 months, but beneficial effects were observed after 12 months. On average, the BFM movement scale scores decreased by 72.5% and Tsui scale scores by 63%. SF-36 showed an improvement in health status by an average of 36% according to eight different health categories. We conclude that chronic high-frequency Gpi stimulation in different types of dystonia is a very effective and safe treatment.