J Kassubek

Publications of J Kassubek

• [Advanced therapy strategies in neurological diseases: present and perspectives].

  Authors: A C Ludolph, J Kassubek

  Der Nervenarzt. 08/2011; 82(8):955-6.

• Reversible Cortical Diffusion Restriction, Hyperperfusion and T2-Hyperintensity Caused by Two Different Types of Epileptic Seizure.

  Authors: A Unrath, H-P Müller, A C Ludolph, J Kassubek

  Clinical neuroradiology. 07/2011;

• Fully automated atlas-based MR imaging volumetry in Huntington disease, compared with manual volumetry.

  Authors: J Kassubek, E H Pinkhardt, A Dietmaier, A C Ludolph, G B Landwehrmeyer, H-J Huppertz

  AJNR. American journal of neuroradiology. 06/2011; 32(7):1328-32.

  The atrophy of the caudate is considered the hallmark of HD-associated neurodegeneration and has high potential as a biomarker in structural MR imaging. This study aimed at comparing automated andThe atrophy of the caudate is considered the hallmark of HD-associated neurodegeneration and has high potential as a biomarker in structural MR imaging. This study aimed at comparing automated and manual caudate volumetry. In this cross-sectional volumetric study in 40 patients with HD and 30 healthy controls, a fully automated caudate measurement by ABV was used for the first time in HD and was directly compared with manual delineation as the generally accepted criterion standard of volumetry. It could be shown that both techniques were able to separate patients and controls to a similar degree. The differences between the 2 volumetric measurements ranged within the limits of agreement; the systematically lower values by manual volumetry were caused by the different assessment of the dorsal caudate tail, which is hard to delineate manually. ABV may be used instead of manual volumetry to quantify caudate volume loss. Additionally, the ABV technique has the advantage of being much faster, is less laborious, and is free of a subjective region-of interest definition. ABV might serve as a tool in potential future clinical trials of disease-modifying treatments in HD.

• Disease severity affects quality of life of hereditary spastic paraplegia patients.

  Authors: S Klimpe, R Schüle, J Kassubek, S Otto, Z Kohl, S Klebe, T Klopstock, S Ratzka, K Karle, L Schöls

  European journal of neurology : the official journal of the European Federation of Neurological Societies. 06/2011; 19(1):168-71.

  Hereditary spastic paraplegia (HSP) causes progressive gait disturbance because of degeneration of the corticospinal tract. To assess its impact on Health-Related Quality of Life (HRQoL), we analyzedHereditary spastic paraplegia (HSP) causes progressive gait disturbance because of degeneration of the corticospinal tract. To assess its impact on Health-Related Quality of Life (HRQoL), we analyzed the correlation of HRQoL with disease severity and clinical symptoms in HSP. HRQoL was assessed by the Short-Form 36 (SF-36) Mental and Physical Component summary scores (MCS and PCS) in 143 German patients with HSP. Disease severity was assessed by the Spastic Paraplegia Rating Scale (SPRS) and landmarks of walking ability. Patients with 'pure' or 'complicated' HSP were compared. Higher SPRS scores indicating higher disease severity correlated significantly with lower PCS (r = -0.63; P < 0.0005) and MCS (r = -0.38; P < 0.0005) scores. MCS and PCS were reduced in patients with 'complicated' forms compared to 'pure' HSP and with decreasing walking ability. HRQoL is substantially impaired in patients with HSP and decreases with disease severity and the presence of 'complicating' symptoms. Patients are most affected by the physical restraints of their disease, but mental health is impaired as well. HRQoL is a valid parameter in HSP that should be considered in upcoming therapeutical trials.

• Alterations of the corpus callosum as an MR imaging-based hallmark of motor neuron diseases.

  Authors: A Unrath, A C Ludolph, J Kassubek

  AJNR. American journal of neuroradiology. 05/2011; 32(5):E90.

• Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis.

  Authors: J Dorst, P Kühnlein, C Hendrich, J Kassubek, A D Sperfeld, A C Ludolph

  Journal of neurology. 12/2010; 258(4):613-7.

  Weight loss is a common phenomenon and an independent prognostic factor in amyotrophic lateral sclerosis (ALS). Several potential causal mechanisms, including intrinsic hypermetabolism and deficientWeight loss is a common phenomenon and an independent prognostic factor in amyotrophic lateral sclerosis (ALS). Several potential causal mechanisms, including intrinsic hypermetabolism and deficient food intake, have been discussed. We investigated the influence of fasting serum glucose, cholesterol, and triglyceride levels at time of diagnosis on survival in ALS. Serum cholesterol (LDL, HDL, and LDL/HDL ratio), triglycerides, and glucose were investigated in 488 patients (age of onset = 57.6 ± 12.6 years) in relation to survival and revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALS-FRS) data. High serum levels of both fasting cholesterol and triglycerides had a significantly positive effect on survival (p < 0.05). We found a median prolonged life expectancy by 14 months for patients with serum triglyceride levels above the median of 1.47 mmol/l. The results suggest that the lipid metabolism and the nutritional status of ALS patients are important prognostic factors. These parameters should be thoroughly monitored during the clinical management of these patients. In case of progressive loss of body weight, a diet rich in lipids and calories should be considered. However, the final decision whether a lipid-rich diet should be recommended to ALS patients can only be based on a double-blind placebo-controlled interventional trial. Our results further imply that lipid-lowering drugs, e.g., statins, should be applied carefully in ALS patients although individual risk considerations must be made.

• [The role of ceruloplasmin in the differential diagnosis of neuropsychiatric disorders].

  Authors: B J Connemann, C Schönfeldt-Lecuona, H-J Maxon, W Kratzer, J Kassubek

  Fortschritte der Neurologie-Psychiatrie. 10/2010; 78(10):582-9.

  The blue copper protein ceruloplasmin has been of interest to psychiatrists for decades following Heilmeyer's observation of elevated serum copper levels in schizophrenic patients.The blue copper protein ceruloplasmin has been of interest to psychiatrists for decades following Heilmeyer's observation of elevated serum copper levels in schizophrenic patients. Immunoturbidimetry, however, does not yield elevated serum ceruloplasmin concentrations in schizophrenia while ceruloplasmin-related oxidase activity appears to be elevated in patients with schizophrenia and reduced in patients with Alzheimer's disease. Low serum concentrations of immuno-turbidimetrically measured ceruloplasmin, and of oxidase activity, are typical of Wilson's disease, Menkes' disease, and aceruloplasminemia, three familial neurodegenerative disorders of pronounced variability, with regard to both genotype and phenotype. Especially patients with Wilson's disease may exhibit behavioural symptoms only over a long period. Heterozygous carriers of Wilson's disease and aceruloplasminaemia may have low serum ceruloplasmin concentrations; they will not develop somatic symptoms, but the significance of these carrier states, or of "hypoceruloplasminaemia", with regard to mental disorders is unknown.

• Delusional infestation induced by piribedil add-on in Parkinson's disease.

  Authors: M Kölle, P Lepping, J Kassubek, C Schönfeldt-Lecuona, R W Freudenmann

  Pharmacopsychiatry. 08/2010; 43(6):240-2.

• Pitfalls in the use of voxel-based morphometry as a biomarker: examples from huntington disease.

  Authors: S M D Henley, G R Ridgway, R I Scahill, S Klöppel, S J Tabrizi, N C Fox, J Kassubek

  AJNR. American journal of neuroradiology. 04/2010; 31(4):711-9.

  VBM is increasingly used in the study of neurodegeneration, and recently there has been interest in its potential as a biomarker. However, although it is largely "automated," VBM is rarelyVBM is increasingly used in the study of neurodegeneration, and recently there has been interest in its potential as a biomarker. However, although it is largely "automated," VBM is rarely implemented consistently across studies, and changing user-specified options can alter the results in a way similar to the very biologic differences under investigation. This work uses data from patients with HD to demonstrate the effects of several user-specified VBM parameters and analyses: type and level of statistical correction, modulation, smoothing kernel size, adjustment for brain size, subgroup analysis, and software version. The results demonstrate that changing these options can alter results in a way similar to the biologic differences under investigation. If VBM is to be useful clinically or considered for use as a biomarker, there is a need for greater recognition of these issues and more uniformity in its application for the method to be both reproducible and valid.

• [On the role of MAO B inhibitors and NMDA antagonists in the therapy of Parkinson's disease].

  Authors: J Kassubek, T Büttner, H Reichmann, P Riederer, J B Schulz, U Wüllner, I Csoti

  Fortschritte der Neurologie-Psychiatrie. 03/2010; 78 Suppl 1:S34-6.

  In this workshop report, the N-methyl-D-aspartate (NMDA) receptor antagonists and the monoamine oxidase (MAO) type B inhibitors are discussed with respect to their role in the pharmacotherapy ofIn this workshop report, the N-methyl-D-aspartate (NMDA) receptor antagonists and the monoamine oxidase (MAO) type B inhibitors are discussed with respect to their role in the pharmacotherapy of Parkinson's Disease (PD). For the NMDA antagonist amantadine, studies demonstrated beneficial effects in various symptoms of the PD complex, while memantine seems to be beneficial in the treatment of cognitive deficits in PD-associated dementia. The MAO B inhibitors selegiline and rasagiline are in use for PD pharmacotherapy; for rasagiline, studies have demonstrated a possible disease-modifying effect. Although not supported by specific controlled studies, a "triple" early therapy is discussed which consists of a dopamine agonist, a MAO B inhibitor and amantadine, in order to try to delay the start of levodopa therapy.

• Comparative analysis of brain structure, metabolism, and cognition in myotonic dystrophy 1 and 2.

  Authors: Y G Weber, R Roebling, J Kassubek, S Hoffmann, A Rosenbohm, M Wolf, P Steinbach, K Jurkat-Rott, H Walter, S N Reske, F Lehmann-Horn, F M Mottaghy, H Lerche

  Neurology. 03/2010; 74(14):1108-17.

  Myotonic dystrophy type 1 and 2 (DM1/DM2) are multisystemic diseases with common cognitive deficits beside the cardinal muscular symptoms. We performed a comprehensive analysis of cerebralMyotonic dystrophy type 1 and 2 (DM1/DM2) are multisystemic diseases with common cognitive deficits beside the cardinal muscular symptoms. We performed a comprehensive analysis of cerebral abnormalities to compare the neuropsychological defects with findings in different imaging methods in the same cohort of patients. Neuropsychological investigations, structural cerebral MRI including brain parenchymal fraction (BPF) and voxel-based morphometry (VBM), and (18)F-deoxy-glucose PET (FDG-PET) were performed in patients (20 DM1 and 9 DM2) and matched healthy controls, and analyzed using statistical parametric mapping (SPM2). DM1 and DM2 patients showed typical neuropsychological deficits with a pronounced impairment of nonverbal episodic memory. Both patient groups showed a reduction of the global gray matter (measured by BPF), which could be localized to the frontal and parietal lobes by VBM. Interestingly, VBM revealed a bilateral hippocampal volume reduction that was correlated specifically to both a clinical score and episodic memory deficits. VBM also revealed a pronounced change of thalamic gray matter. White matter lesions were found in >50% of patients and their extent was correlated to psychomotor speed. FDG-PET revealed a frontotemporal hypometabolism, independent of the decrease in cortical gray matter. All abnormalities were similar in both patient groups but more pronounced for DM1. Our results suggest that 1) some of the characteristic cognitive deficits of these patients are linked to specific structural cerebral changes, 2) decreases in gray matter and metabolism are independent processes, and 3) the widespread brain abnormalities are more pronounced in DM1.

• [Restless legs, restless nights: therapeutic options in RLS]

  Authors: J Kassubek, A Unrath

  MMW Fortschritte der Medizin. 04/2009; 151(13):65-7, 69.

• Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options.

  Authors: A C Ludolph, J Kassubek, B. G. Landwehrmeyer, E Mandelkow, E M Mandelkow, D J Burn, D. Caparros-Lefebvre, K. A. Frey, J G de Yebenes, T Gasser [......] T. Reum, A. Saint-Raymond, J C Steele, M. Tolnay, H Tumani, J C van Swieten, M. T. Vanier, J. P. Vonsattel, S. Wagner, Z K Wszolek

  European journal of neurology : the official journal of the European Federation of Neurological Societies. 04/2009; 16(3):297-309.

  Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system. TheseTauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system. These pathologic characteristics suggest shared pathogenetic pathways and possible molecular targets for disease-modifying therapeutic interventions. Natural history studies, for instance, in progressive supranuclear palsy, frontotemporal dementia with parkinsonism linked to chromosome 17, corticobasal degeneration, and Niemann-Pick disease type C as well as in amyotrophic lateral sclerosis/Parkinson-dementia complex permit clinical characterization of the disease phenotypes and are crucial to the development and validation of biological markers for differential diagnostics and disease monitoring, for example, by use of neuroimaging or proteomic approaches. The wide pathologic and clinical spectrum of the tauopathies with parkinsonism is reviewed in this article, and perspectives on future advances in the understanding of the pathogenesis are given, together with potential therapeutic strategies.

• The contribution of white and gray matter differences to developmental dyslexia: Insights from DTI and VBM at 3.0T.

  Authors: C Steinbrink, K Vogt, A Kastrup, H P Müller, F D Juengling, J Kassubek, A Riecker

  Neuropsychologia. 12/2008; 46(13):3170-8.

  Developmental dyslexia is one of the most common neuropsychological disorders in children and adults. Only few data are available on the pathomechanisms of this specific dysfunction, assuming - amongDevelopmental dyslexia is one of the most common neuropsychological disorders in children and adults. Only few data are available on the pathomechanisms of this specific dysfunction, assuming - among others - that dyslexia might be a disconnection syndrome of anterior and posterior brain regions involved in phonological and orthographic aspects of the reading process, as well as in the integration of phonemes and graphemes. Therefore, diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) were used to verify the hypothesis of altered white and gray matter structure in German dyslexic adults. DTI revealed decreased fractional anisotropy (FA) in bilateral fronto-temporal and left temporo-parietal white matter regions (inferior and superior longitudinal fasciculus). Significant correlations between white matter anisotropy and speed of pseudoword reading were found. In dyslexics, gray matter volumes (as measured by VBM) were reduced in the superior temporal gyrus of both hemispheres. So far, our results, based on a combined analysis of white and gray matter abnormalities, provide exceedingly strong evidence for a disconnection syndrome or dysfunction of cortical areas relevant for reading and spelling. Thus, we suggest that this imbalance of neuronal communication between the respective brain areas might be the crucial point for the development of dyslexia.

• Eye-head coordination in moderately affected Huntington's Disease patients: do head movements facilitate gaze shifts?

  Authors: W Becker, R Jürgens, J Kassubek, D Ecker, B Kramer, B Landwehrmeyer

  Experimental brain research. Experimentelle Hirnforschung. Experimentation cerebrale. 09/2008;

  In addition to many other symptoms, Huntington's Disease (HD) also causes an impairment of oculomotor functions. In particular, saccadic eye movements become progressively slower and more difficultIn addition to many other symptoms, Huntington's Disease (HD) also causes an impairment of oculomotor functions. In particular, saccadic eye movements become progressively slower and more difficult to initiate; ultimately, patients are forced to recur to large head thrusts as means to initiate gaze shifts. We wondered whether, as a precursor of this condition, head movements would facilitate gaze shifts already in early stages of the disease. We studied horizontal head movements and eye-head coordination in 29 early stage HD patients (Ps) and 24 age matched controls (Cs). Subjects tracked random horizontal steps of visual or auditory targets while their heads were either stabilised (saccade amplitudes </=40 degrees ) or free to move (amplitudes </=160 degrees ). Subjects were to react either immediately (reactive mode), or wait until a go signal was sounded (delayed mode), or by antisaccades. Ps' head velocity was found to depend on the age of disease onset in a similar way as their saccadic eye velocity does, being clearly reduced in early affected Ps, but increasing to normal levels in lately affected Ps. Yet, saccade and head velocity were only loosely correlated although both exhibited a negative correlation with the severity of Ps' genetic condition (number of Ps' CAG repeats). Eye-head coordination turned out to be identical in Ps and Cs except for quantitative differences caused by the lower saccade and head velocities of Ps. Specifically, the timing between head and eyes and the head contribution to gaze shifts were similar in both groups. Moreover, preventing head movements did not affect the saccade latency or accuracy of Ps. Although Ps made more small involuntary head movements in this condition than Cs, these movements were not instrumental in generating saccades since they occurred only late after saccade onset. Thus, the head manoeuvres of severely affected patients must be considered a late adaptive behaviour. Finally, the ability of both Ps and Cs to suppress immediate reactions in the delayed and antisaccade conditions diminished as target distance decreased, with failure rates in Ps being much larger than in Cs. Unlike eye and head velocity, these failure rates were not correlated with age and, by the same token, neither with the variations in head and eye velocity nor with the number of CAG repeats. Hence, the pattern of brain areas prominently affected by HD is likely to vary significantly among individuals.

• Is spinal epidural lipomatosis an MRI-based diagnosis with clinical implications? A retrospective analysis.

  Authors: E H Pinkhardt, A-D Sperfeld, V Bretschneider, A Unrath, A C Ludolph, J Kassubek

  Acta neurologica Scandinavica. 07/2008; 117(6):409-14.

  OBJECTIVES: Magnetic resonance imaging (MRI) is considered the most sensitive modality for evaluating spinal epidural lipomatosis (SEL) in vivo. The aim of this study was to compare the existing MRIOBJECTIVES: Magnetic resonance imaging (MRI) is considered the most sensitive modality for evaluating spinal epidural lipomatosis (SEL) in vivo. The aim of this study was to compare the existing MRI classifications of SEL and to reevaluate the clinico-radiological correlation of SEL as a pathological entity. MATERIALS AND METHODS: Measurements of the cervical, thoracic and lumbar spine were performed in a retrospective setting within 1406 data sets from the digital MRI archives. RESULTS: It could be shown that the existing MRI classifications developed for different spinal regions complemented each other. However, there was no distinct correlation of these MRI findings with clinical symptoms because other morphological changes existed that probably caused the patients' complaints. CONCLUSION: Existing SEL classifications developed either for the lumbar or the thoracic spine were found to be applicable to both regions, but the very vague association with clinical symptoms should caution against premature conclusions with respect to the clinical significance of SEL.

• SPG10 is a rare cause of spastic paraplegia in European families.

  Authors: R Schüle, B P H Kremer, J Kassubek, M Auer-Grumbach, V Kostic, T Klopstock, S Klimpe, S Otto, S Boesch, B P van de Warrenburg, L Schöls

  Journal of neurology, neurosurgery, and psychiatry. 05/2008; 79(5):584-7.

  BACKGROUND: SPG10 is an autosomal dominant form of hereditary spastic paraplegia (HSP), which is caused by mutations in the neural kinesin heavy chain KIF5A gene, the neuronal motor of fastBACKGROUND: SPG10 is an autosomal dominant form of hereditary spastic paraplegia (HSP), which is caused by mutations in the neural kinesin heavy chain KIF5A gene, the neuronal motor of fast anterograde axonal transport. Only four mutations have been identified to date. OBJECTIVE: To determine the frequency of SPG10 in European families with HSP and to specify the SPG10 phenotype. PATIENTS AND METHODS: 80 index patients from families with autosomal dominant HSP were investigated for SPG10 mutations by direct sequencing of the KIF5A motor domain. Additionally, the whole gene was sequenced in 20 of these families. RESULTS: Three novel KIF5A mutations were detected in German families, including one missense mutation (c.759G>T, p.K253N), one in frame deletion (c.768_770delCAA, p.N256del) and one splice site mutation (c.217G>A). Onset of gait disturbance varied from infancy to 30 years of age. All patients presented clinically with pure HSP, but a subclinical sensory-motor neuropathy was detected by neurophysiology studies. CONCLUSIONS: SPG10 accounts for approximately 3% of European autosomal dominant HSP families. All mutations affect the motor domain of kinesin and thus most likely impair axonal transport. Clinically, SPG10 is characterised by spastic paraplegia with mostly subclinical peripheral neuropathy.

• Automatic curvilinear reformatting of three-dimensional MRI data of the cerebral cortex.

  Authors: H J Huppertz, J Kassubek, D-M Altenmüller, T Breyer, S Fauser

  NeuroImage. 02/2008; 39(1):80-6.

  Curvilinear reformatting of three-dimensional (3D) MRI data of the cerebral cortex is a well-established tool which improves the display of the gyral structure, permits a precise localization ofCurvilinear reformatting of three-dimensional (3D) MRI data of the cerebral cortex is a well-established tool which improves the display of the gyral structure, permits a precise localization of lesions, and helps to identify subtle abnormalities difficult to detect in planar slices due to the brain's complex convolutional pattern. However, the method is time consuming because it requires interactive manual delineation of the brain surface contour. Therefore, a novel technique for automatic curvilinear reformatting is presented. A T1-weighted MRI volume data set is normalized using SPM2. Due to the normalization to a common stereotactic space, predefined masks can be applied to cover skull and outer brain regions in different depths from the brain surface. Thereby, the outer brain regions are subsequently removed in 2-mm layers parallel to the brain surface like 'peeling an onion'. The serial convex planes enclosing the residual inner part of the brain are presented 3-dimensionally. If necessary (e.g., for intraoperative navigation), the normalized data can be transferred to native space by inverse normalization. Compared to cross-sectional images, curvilinear reformatting offers a markedly superior visualization of topographic relations between lesions and cortical structures, helps to detect subtle cortical malformations and to assess the spatial extent of lesions, thus allowing a better planning of neurosurgical procedures. Compared to alternative methods, it is largely based on freely available software and does not require observer-dependent manual input. In conclusion, we present a simple, easy-to-use and fully automated method for curvilinear reformatting of 3D MRI.

• Computer-based 3D MR imaging analysis in amyotrophic lateral sclerosis: common and specific factors among studies.

  Authors: A Unrath, J Kassubek

  AJNR. American journal of neuroradiology. 11/2007; 28(9):1626; author reply 1627.

• Voxel-based morphometry indicates relative preservation of the limbic prefrontal cortex in early Huntington disease.

  Authors: M Mühlau, A Weindl, A M Wohlschläger, C Gaser, M Städtler, M Valet, C Zimmer, J Kassubek, A Peinemann

  Journal of neural transmission (Vienna, Austria : 1996). 04/2007; 114(3):367-72.

  In Huntington disease (HD), both the genetic defect and mutant gene product huntington are known but the exact mechanisms that lead to neuronal loss are poorly understood. Until now, the distributionIn Huntington disease (HD), both the genetic defect and mutant gene product huntington are known but the exact mechanisms that lead to neuronal loss are poorly understood. Until now, the distribution of tissue loss throughout the brain has been investigated intensively. Here we searched for areas that, antipodal to the striatum, display grey-matter (GM) preservation. We performed high resolution T1-weighted magnetic resonance imaging and voxel-based morphometry in 46 patients in early HD and 46 healthy controls. We applied an analysis of covariance (ANCOVA) model with the total GM volume of each participant as covariate. In accordance with earlier reports, group comparisons revealed GM decrease in the striatum, insula, and thalamus as well as in dorsolateral frontal and occipital areas. In contrast, the limbic prefrontal cortex displayed GM preservation. Our findings support hypotheses that postulate differential involvement of frontosubcortical circuits in the pathophysiology of HD.