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J Kassubek

Publications and source records attributed to J Kassubek.

At least 19 recordsLinked to original sources
PubMed2007

[Transient global amnesia (TGA) during an oral provocation test].

After the oral administration of the COX 2 inhibitor rofecoxib (Vioxx) as part of an oral provocation test, a 64-year-old woman developed acute anterograde and retrograde amnesia which lasted for several hours. The patient did not show symptoms of anaphylaxis. Neurological examination did not reveal focal symptoms or an epileptic seizure. Diffusion-weighted magnetic resonance imaging only showed a small region of increased signal intensity in the left hippocampus. The patient thus had no anaphylactic drug reaction, but a transient global amnesia (TGA) or amnestic episode. TGA is an acute, reversible, cerebral dysfunctional state which lasts from 1 h up to maximally 24 h and which is associated with anterograde and retrograde amnesia. While about half of the cases appear to occur spontaneously, other cases are preceded by physically or emotionally stressful events. In our patient it may have been the emotional distress caused by the oral provocation testing that has triggered the TGA. When TGA occurs during oral challenge of drugs, we recommend repeating the oral challenge of the tested drug.

Administration, Oral↗
PubMed2006

High frequency of partial SPAST deletions in autosomal dominant hereditary spastic paraplegia.

BACKGROUND: Hereditary spastic paraplegia (HSP) is a genetically heterogeneous neurodegenerative disease. The most frequent cause of autosomal dominant HSP is mutation of SPAST (SPG4 locus), but additional pedigrees remain mutation negative by conventional screening despite linkage to SPG4. OBJECTIVE: To determine the frequency of genomic copy number aberrations of SPAST in autosomal dominant HSP. METHODS: We developed and validated a multiplex ligation-dependent probe amplification assay targeting SPAST and SPG3A, another gene frequently involved in autosomal dominant HSP. In a multicenter study we subsequently investigated 65 index patients with autosomal dominant HSP, all of whom had previously been screened negative for SPAST mutations. Independent secondary samples, additional family members, and cDNA were analyzed to confirm positive findings. RESULTS: Aberrant MLPA profiles were identified in 12 cases (18%). They exclusively affect SPAST, represent deletions, segregate with the disease, and are largely pedigree specific. Internal SPAST deletions entail expression of correspondingly shortened transcripts, which vary in stability. Age at onset in SPAST deletion carriers does not differ from that associated with other SPAST mutations. CONCLUSIONS: Partial SPAST deletions, but not SPAST amplifications and SPG3A copy number aberrations, represent an underestimated cause of autosomal dominant hereditary spastic paraplegia. Partial SPAST deletions are likely to act via haploinsufficiency.

Adenosine Triphosphatases↗
PubMed2006

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

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 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.

Adult↗
PubMed2006

The Spastic Paraplegia Rating Scale (SPRS): a reliable and valid measure of disease severity.

OBJECTIVE: To develop and evaluate a clinical Spastic Paraplegia Rating Scale (SPRS) to measure disease severity and progression. METHODS: A 13-item scale was designed to rate functional impairment occurring in pure forms of spastic paraplegia (SP). Additional symptoms constituting a complicated form of SP are recorded in an inventory. Two independent patient cohorts were evaluated in a two-step validation procedure. RESULTS: Application of SPRS requires less than 15 minutes and does not require any special equipment, so it is suitable for an outpatient setting. Interrater agreement of SPRS was high (intraclass correlation coefficient = 0.99). Reliability was further supported by high internal consistency (Cronbach alpha = 0.91). SPRS values were almost normally distributed without apparent floor or ceiling effect. Construct validity was shown by high correlation of SPRS to Barthel Index and the International Cooperative Ataxia Rating Scale (convergent validity) and low correlation to Mini-Mental Status Examination (discriminant validity). CONCLUSION: The Spastic Paraplegia Rating Scale is a reliable and valid measure of disease severity.

Adolescent↗
PubMed2006

Screening for cognitive impairment in Parkinson's disease--which marker relates to disease severity?

The frequency and pattern of cognitive deficits in Parkinson's disease (PD) is under discussion. We assessed 157 consecutive subjects with PD (66.4 +/- 8.9 years (mean +/- standard deviation); average duration of disease 3.5 +/- 1.3 years; average Hoehn and Yahr stage 2.4 +/- 0.9) diagnosed in centers specialized for the diagnosis and treatment of PD with brief tests for memory (Memory Impairment Screen), attention (Letter Sorting Test) and semantic fluency (category animals). Impaired memory was observed in about one half of the subjects regardless of severity of disease as assessed by staging according to Hoehn and Yahr. With greater severity, free recall was impaired and subjects required the cues to recall the items. Performance in the Letter Sorting Test and the semantic fluency task declined with increasing Hoehn and Yahr stage, also. We conclude that cognitive deficits are frequent in PD. Further analyses reveal that even in selected screening tests (e.g. semantic fluency) a significant impairment with increasing disease severity (Hoehn and Yahr stage) as opposed to disease duration alone can be demonstrated.

Aged↗
PubMed2006

Brain atrophy in pure and complicated hereditary spastic paraparesis: a quantitative 3D MRI study.

Hereditary spastic paraparesis (HSP) is a heterogeneous group of neurodegenerative disorders with progressive lower limb spasticity, categorized into pure (p-HSP) and complicated forms (c-HSP). The purpose of this study was to evaluate if brain volumes in HSP were altered compared with a control population. Brain volumes were determined in patients suffering from HSP, including both p-HSP (n = 21) and c-HSP type (n = 12), and 30 age-matched healthy controls, using brain parenchymal fractions (BPF) calculated from 3D MRI data in an observer-independent procedure. In addition, the tissue segments of grey and white matter were analysed separately. In HSP patients, BPF were significantly reduced compared with controls both for the whole patient group (P < 0.001) and for both subgroups, indicating considerable brain atrophy. In contrast to controls who showed a decline of brain volumes with age, this physiological phenomenon was less pronounced in HSP. Therefore, global brain parenchyma reduction, involving both grey and white matter, seems to be a feature in both subtypes of HSP. Atrophy was more pronounced in c-HSP, consistent with the more severe phenotype including extramotor involvement. Thus, global brain atrophy, detected by MRI-based brain volume quantification, is a biological marker in HSP subtypes.

Adult↗
PubMed2005

Isolated blood-cerebrospinal fluid barrier dysfunction: prevalence and associated diseases.

OBJECTIVE: An isolated dysfunction of the blood-CSF barrier is characterised by an abnormal elevation of the albumin CSF/serum concentration ratio (Q(alb)) without any other pathological CSF findings. Although common in routine CSF analysis, the clinical significance of an isolated barrier dysfunction frequently remains unclear. We examined neurological disorders associated with an isolated elevation of Q(alb) to identify possible determinants of blood-CSF barrier dysfunction. METHODS: 367 patients (124 women, 243 men, median age 60. 0 years) out of 3,873 patients receiving diagnostic lumbar puncture at the University Hospital of Ulm (Germany) showed an isolated dysfunction of the blood-CSF barrier. Clinical data as well as MRI findings of these patients were analysed. RESULTS: Isolated barrier dysfunction occurred most frequently (> 30%) in Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), normal pressure hydrocephalus (NPH), lumbar spinal stenosis, and polyneuropathy (PNP). In patients who showed no other evidence of neurological disease, isolated barrier dysfunction was found in 14. 9% of cases. The extent of barrier dysfunction was most prominent in brain tumours, GBS, and CIDP. There was a significant correlation of Q(alb) with both weight and body mass index (BMI). CONCLUSIONS: Although isolated barrier dysfunction may be found in a variety of neurological diseases, it is especially frequent in GBS, CIDP, NPH, spinal canal stenosis, and PNP. In these patients, disease-related mechanisms contributing to barrier dysfunction are likely. Moreover, barrier function seems to be influenced by disease-independent determinants like weight and BMI.

Albumins↗
PubMed2005

[Hereditary hemorrhagic telangiectasia. A rare treatable cause of stroke].

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease of the vascular connective tissue. Pulmonary arteriovenous and cerebral vascular malformations are risk factors for serious neurological complications such as paradoxical embolism and intracranial hematomas. We describe two patients with HHT and pulmonary arteriovenous malformations suffering from stroke caused by paradoxical embolism. In both cases, fistulas were successfully treated by embolisation and no further cerebral ischemic events occurred. In ischemic strokes of unknown origin, HHT should be considered as a possible diagnosis with effective treatment options.

Adult↗
PubMed2005

Tau protein level in cerebrospinal fluid is increased in patients with early multiple sclerosis.

Axonal damage has been proposed as the major substrate of permanent clinical disability in multiple sclerosis. Tau protein, a microtubule-associated protein localised in neuronal axons, may serve as a biochemical surrogate marker to evaluate axonal damage in vivo. We intended to determine the extent of axonal damage in different stages and clinical subtypes of MS by investigating cerebrospinal fluid tau concentrations. Tau was measured using an immunoassay in 35 patients with relapsing-remitting MS, eight patients with secondary progressive MS, nine patients with primary progressive MS, 50 patients with clinically isolated syndrome suggestive of early MS and 46 normal controls. Cerebrospinal fluid tau was significantly elevated in MS compared with normal controls (median 206.0 pg/mL versus 152.0 pg/mL; P = 0.002). No significant difference among different subtypes of MS could be detected, although highest levels were found in very early disease stages. There was a significant elevation of CSF tau among patients with gadolinium-enhancing brain lesions in magnetic resonance imaging (P = 0.02) and a tendency towards higher CSF tau levels in patients with pronounced intrathecal IgG synthesis, supporting the notion that axonal damage is influenced by inflammatory activity.

Adolescent↗
PubMed2004

Diffusion-weighted MRI during early global cerebral hypoxia: a predictor for clinical outcome?

OBJECTIVES: As prognostic assessment of prolonged cerebral hypoxia is often difficult on clinical grounds, a tool for an early prognosis of clinical outcome is desirable. PATIENTS AND METHODS: In a prospective study, we investigated the prognostic value of diffusion-weighted MRI (DWI) in 12 patients within 36 h after global cerebral hypoxia. Results of DWI including apparent diffusion coefficient maps (ADC) were analyzed and related to the clinical outcome after 6 months, in comparison with conventional magnetic resonance imaging (cMRI). RESULTS: Three patients with a short resuscitation time showed normal findings in cMRI and DWI and a good recovery. In seven patients, DWI revealed multiple large hyperintense areas although cMRI was normal. In two patients, large diffuse lesions were observed in DWI which were also found in cMRI. All of these nine patients developed a vegetative state in the follow-up examination. CONCLUSION: Pathological DWI during the early phase after cerebral hypoxia might be superior to cMRI as a predictor of a worse clinical outcome.

Adult↗
PubMed2004

Topography of cerebral atrophy in early Huntington's disease: a voxel based morphometric MRI study.

OBJECTIVES: To analyse grey matter changes in early stages of Huntington's disease using magnetic resonance imaging (MRI) and the technique of voxel based morphometry (VBM). METHODS: Forty four patients with a molecularly confirmed clinical diagnosis of Huntington's disease based on the presence of motor signs were included in the study. Patients were clinically rated using the Unified Huntington's Disease Rating Scale; all were in early clinical stages of the disease (that is, Shoulson stages I and II). High resolution volume rendering MRI scans (MP-RAGE) were acquired. MRI data were volumetrically analysed in comparison to an age matched normal database by VBM, using statistical parametric mapping (SPM99). RESULTS: In Huntington's disease, robust regional decreases in grey matter density (p<0.001, corrected for multiple comparisons)-that is, atrophy-were found bilaterally in striatal areas as well as in the hypothalamus and the opercular cortex, and unilaterally in the right paracentral lobule. The topography of striatal changes corresponded to the dorso-ventral gradient of neuronal loss described in neuropathological studies. Stratification according to clinical severity showed a more widespread involvement extending into the ventral aspects of the striatum in the group of more severely affected patients. CONCLUSIONS: The topography of cerebral volume changes associated with Huntington's disease can be mapped using VBM. It can be shown that cerebral grey matter changes co-vary with clinical severity and CAG repeat length.

Adult↗
PubMed2003

Automated detection of gray matter malformations using optimized voxel-based morphometry: a systematic approach.

Malformations of cortical development (MCD) are a recognized cause of epilepsy. Their special significance lies in the fact that, once detected and delineated, they are amenable to surgical removal. However, diagnosis from high-resolution MRI is still difficult, time-consuming, and highly dependent on individual expertise. We have recently proposed a simple procedure to detect cortical dysplasias, using automated procedures available within SPM99 (Wellcome Department, University College London, UK). Here, we aimed to systematically determine the best combination of processing parameters, using an optimized voxel-based morphometry approach. We included 20 patients with a known MCD and compared them to a normal database of 53 healthy, age- and gender-matched controls. The approaches taken during spatial normalization and a number of other parameters were systematically altered in order to find the best combination of parameters. Overall, 99 different approaches were evaluated in different ways. As far as possible, automatic processing and evaluation steps were used. With the number of candidate regions for MCD limited to five per patient, the best approaches resulted in the correct identification of up to 16 of 20 malformations. However, a number of approaches failed to perform well. The reasons for these failures and the implications this has for other studies are discussed. We conclude that voxel-based morphometry is able to detect cortical malformations with a high degree of accuracy. However, specific problems seem to arise when using an optimized protocol for voxel-based morphometry, indicating that this protocol may not be optimal for all voxel-based studies on brain morphology. Our approach, involving systematic alterations of parameters and evaluation, may be useful for other studies.

Adolescent↗
PubMed2002

Determination of hemisphere dominance for language: comparison of frontal and temporal fMRI activation with intracarotid amytal testing.

The reliability of frontal and temporal fMRI activations for the determination of hemisphere language dominance was evaluated in comparison with intracarotid amytal testing (IAT). Twenty-two patients were studied by IAT (bilateral in 13, unilateral in 9 patients) and fMRI using a paradigm requiring semantic decisions. Global and regional (frontal and temporoparietal) lateralisation indices (LI) were calculated from the number of activated (r>0.4) voxels in both hemispheres. Frontolateral activations associated with the language task were seen in all patients, temporoparietal activations in 20 of 22. Regional LI corresponded better with IAT results than global LI. Frontolateral LI were consistent with IAT in all patients with bilateral IAT (including three patients with right dominant and one patient with bilateral language representation) and were not conflicting in any of the patients with unilateral IAT. Temporoparietal LI were discordant with IAT in two patients with atypical language representation. In the determination of hemisphere dominance for language, regional analysis of fMRI activation is superior to global analysis. In cases with clear-cut fMRI lateralisation, i.e. consistent lateralised activation of frontal and temporoparietal language zones, IAT may be unnecessary. FMRI should be performed prior to IAT in all patients going to be operated in brain regions potentially involved in language.

Adolescent↗
PubMed2002

[Historical review and recent research trends of the antidepressant repetitive transcranial magnetic stimulation (rTMS)].

The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) has been studied intensively over the last years. Numerous studies worldwide yielded variable results ranging from ineffectivity to an efficacy rate of more than 50 % for the reduction of depressive symptoms. A comparison of the effectiveness of TMS across studies is difficult due to the variety of chosen stimulation parameters, different inclusion criteria, and different designs. The discrepancies in results could be partially in account to these factors. From a pathophysiological point of view, there are no empirically justified parameters published carrying out an antidepressant TMS. Further studies are required to find optimal stimulation parameters using complementary methods like functional imaging techniques or regarding other factors that could interfere with its efficacy. An overview of studies published in the last ten years, a critical analysis of stimulation procedures and protocols, and possible future perspectives of this method are reviewed in this article.

Brain↗
PubMed2001

Reversible coma with raised intracranial pressure: an unusual clinical manifestation of CADASIL.

A 50-year-old woman presented with recurrent episodes of headache, nausea and disturbed consciousness that were fully reversible within a few days. Clinical and radiological findings suggested raised intracranial pressure, which on one occasion was confirmed by intracranial pressure monitoring. Magnetic resonance imaging performed in the asymptomatic interval disclosed a diffuse leukoencephalopathy. Brain biopsy surprisingly revealed the typical vascular changes of CADASIL and subtle endothelial alterations. The white matter showed edematous changes and reactive gliosis. Mutational analysis of the Notch3 gene revealed a previously unreported mutation. We suggest that a transient disturbance of the blood-brain barrier related to the underlying vascular pathology may have caused this unusual presentation of CADASIL.

Coma↗
PubMed2001

Hypermetabolism in the ventrolateral thalamus in unilateral Parkinsonian resting tremor: a positron emission tomography study.

Tremorogenesis in Parkinson's disease (PD) is assumed to involve a cerebral network including the thalamus. An imaging study was performed on eight PD patients with strictly unilateral resting tremor using fluorodeoxyglucose positron emission tomography coregistered to 3-dimensional magnetic resonance imaging. Increased metabolic activity of high statistical significance (P<0.001) was found in the anterior ventrolateral nuclear group of the thalamus located contralateral to the tremor side. The metabolic changes significantly covaried with tremor amplitudes. For the first time, it could be demonstrated that thalamic metabolic changes associated with tremor in PD are localized in the ventral lateral anterior nucleus (VLa). The results are discussed with respect to previous studies on tremor generation.

Aged↗
PubMed2001

Relationship between saccadic eye movements and cortical activity as measured by fMRI: quantitative and qualitative aspects.

We investigated the quantitative relationship between saccadic activity (as reflected in frequency of occurrence and amplitude of saccades) and blood oxygenation level dependent (BOLD) changes in the cerebral cortex using functional magnetic resonance imaging (fMRI). Furthermore, we investigated quantitative changes in cortical activity associated with qualitative changes in the saccade task for comparable levels of saccadic activity. All experiments required the simultaneous acquisition of eye movement and fMRI data. For this purpose we used a new high-resolution limbus-tracking technique for recording eye movements in the magnetic resonance tomograph. In the first two experimental series we varied both frequency and amplitude of saccade stimuli (target jumps). In the third series we varied task difficulty; subjects performed either pro-saccades or anti-saccades. The brain volume investigated comprised the frontal and supplementary eye fields, parietal as well as striate cortex, and the motion sensitive area of the parieto-occipital cortex. All these regions showed saccade-related BOLD responses. The responses in these regions were highly correlated with saccade frequency, indicating that repeated processing of saccades is integrated over time in the BOLD response. In contrast, there was no comparable BOLD change with variation of saccade amplitude. This finding speaks for a topological rather than activity-dependent coding of saccade amplitudes in most cortical regions. In the experiments comparing pro- vs anti-saccades we found higher BOLD activation in the "anti" task than in the "pro" task. A comparison of saccade parameters revealed that saccade frequency and cumulative amplitude were comparable between the two tasks, whereas reaction times were longer in the "anti" task than the pro task. The latter finding is taken to indicate a more demanding cortical processing in the "anti" task than the "pro" task, which could explain the observed difference in BOLD activation. We hold that a quantitative analysis of saccade parameters (especially saccade frequency and latency) is important for the interpretation of the BOLD changes observed with visual stimuli in fMRI.

Adult↗