Publications by authors named "Jakob Rath"

23 Publications

  • Page 1 of 1

Cerebrospinal fluid analysis in Guillain-Barré syndrome: value of albumin quotients.

J Neurol 2021 Mar 2. Epub 2021 Mar 2.

Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Background: Albuminocytologic dissociation in cerebrospinal fluid (CSF) is a diagnostic hallmark of Guillain-Barré syndrome (GBS). Compared to CSF total protein (TP), the CSF/serum albumin quotient (Qalb) has the advantage of method-independent reference ranges. Whether the diagnostic yield differs between Qalb and CSF-TP is currently unknown.

Methods: We retrospectively analyzed the diagnostic yield (i.e., a value above the URL indicating blood-nerve barrier dysfunction) of Qalb and CSF-TP levels in patients with GBS. We evaluated two different equations (Reiber's and Hegen's) for age-adjusted URLs of Qalb and compared results to CSF-TP using the standard URL of 0.45 g/L as well as age-adjusted URLs (by decade of age). Additionally, multivariable logistic regression analysis was used to assess the effect of clinical factors on the diagnostic yield.

Results: We analyzed 110 patients [62% males; median age 48 (IQR 35-58)] with sensorimotor (68), motor (16), sensory (12) and localized (8) GBS as well as Miller Fisher syndrome (6). Qalb and CSF-TP were highly correlated (r = 0.95, p < 0.001). The diagnostic yield of Qalb was 65% with Reiber's and 47% with Hegen's age-adjusted URLs compared to 66% with the fixed CSF-TP URL of 0.45 g/L and 49% with age-adjusted CSF-TP URLs. A longer duration from clinical onset to lumbar puncture was associated with a higher diagnostic yield.

Conclusion: Qalb strongly correlates with CSF-TP in patients with GBS with a similar diagnostic yield for the detection of a blood-nerve barrier dysfunction. However, the diagnostic yield of both values is lower when using more recent age-adjusted URLs and at earlier timepoints.
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http://dx.doi.org/10.1007/s00415-021-10479-9DOI Listing
March 2021

Nerve conduction studies in Guillain-Barré syndrome: Influence of timing and value of repeated measurements.

J Neurol Sci 2021 01 13;420:117267. Epub 2020 Dec 13.

Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.

Objective: Nerve conduction studies (NCS) are essential to differentiate between demyelinating and axonal subtypes in Guillain-Barré syndrome (GBS). However, it is debated to which extent the delay of NCS after symptom onset and repeated measurements during the disease course influence the diagnostic accuracy.

Methods: We evaluated NCS in 93 patients with a classical GBS applying two widely used criteria (Hadden's and Rajabally's). The initial measurements after symptom onset were compared to follow-up studies where available (n = 43). We analyzed the influence of NCS timing after symptom onset and clinical severity on fulfilling the electrophysiological criteria for axonal or demyelinating subtypes and evaluated the impact of repeated measurements. We further evaluated the presence of reversible conduction failure.

Results: A higher GBS disability scale at nadir correlated with a successful subclassification whereas the delay of the first NCS after symptom onset did not influence the diagnostic yield (75% for Hadden's and 68% for Rajabally's criteria for the first assessment). A second measurement allowed the additional successful classification in 19% and 14% of patients, respectively. On the other hand, a repeated measurement in patients with an initial successful classification resulted in a different subtype in 5% and 7%, respectively. Reversible conduction failure was found in 7% of patients.

Conclusion: Clinical severity but not timing of NCS influenced the fulfilment of electrophysiological criteria for either the axonal or demyelinating subtype. Repeated electrophysiological measurements led to a further specification or a change in subtype classification in a relevant proportion of patients.
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http://dx.doi.org/10.1016/j.jns.2020.117267DOI Listing
January 2021

Pathomechanisms and Clinical Implications of Myasthenic Syndromes Exacerbated and Induced by Medical Treatments.

Front Mol Neurosci 2020 14;13:156. Epub 2020 Aug 14.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Myasthenic syndromes are typically characterized by muscle weakness and increased fatigability due to an impaired transmission at the neuromuscular junction (NMJ). Most cases are caused by acquired autoimmune conditions such as myasthenia gravis (MG), typically with antibodies against the acetylcholine receptor (AChR). Different drugs are among the major factors that may complicate pre-existing autoimmune myasthenic conditions by further impairing transmission at the NMJ. Some clinical observations are substantiated by experimental data, indicating that presynaptic, postsynaptic or more complex pathomechanisms at the NMJ may be involved, depending on the individual compound. Most robust data exist for the risks associated with some antibiotics (e.g., aminoglycosides, ketolides, fluoroquinolones) and cardiovascular medications (e.g., class Ia antiarrhythmics, beta blockers). Apart from primarily autoimmune-mediated disorders of the NMJ, myasthenic manifestations may also be triggered by medical treatments that induce an autoimmune reaction. Most notably, there is growing evidence that the immune checkpoint inhibitors (ICI), a modern class of drugs to treat various malignancies, represent a relevant risk factor to develop severe and progressive medication-induced myasthenia via an immune-mediated mechanism. From a clinical perspective, it is of utmost importance for the treating physicians to be aware of such adverse treatment effects and their consequences. In this article, we aim to summarize existing evidence regarding the key molecular and immunological mechanisms as well as the clinical implications of medication-aggravated and medication-induced myasthenic syndromes.
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http://dx.doi.org/10.3389/fnmol.2020.00156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457047PMC
August 2020

Subgroup stratification and outcome in recently diagnosed generalized myasthenia gravis.

Neurology 2020 09 8;95(10):e1426-e1436. Epub 2020 Jul 8.

From the Department of Neurology (M.T., E.H., J.R., M.F., H.C., F.Z.), Medical University of Vienna; and Department of Neurology (E.-M.M., W.N.L.), Medical University of Innsbruck, Innsbruck, Austria.

Objective: To describe disease outcomes of myasthenia gravis (MG) subgroups and which factors influence outcomes by reviewing individual patient records of a representative cohort.

Methods: We performed a retrospective analysis of 199 patients with generalized MG and disease onset after the year 2000 who were treated at 2 tertiary referral centers in Austria. We stratified patients as early- and late-onset acetylcholine receptor antibody-positive, muscle-specific tyrosine kinase (MuSK) antibody-positive, and seronegative patients and patients with thymoma regardless of antibody status. We evaluated patients' symptom severity and treatment regimens and the occurrence of life-threatening events at yearly time points for up to 10 years.

Results: Minimal manifestation status or better was eventually achieved and sustained for >1 year by 125 (63%) patients. Forty percent (66 of 165 patients) showed an early response to treatment, which predicted a benign disease course later on. In contrast, 19% of patients, who remained symptomatic for 2 years after disease onset despite immunosuppressive therapy, were more treatment resistant in the following years. The strongest predictor of outcome was the diagnostic subgroup. Patients with MuSK-MG had a much better outcome than previously reported.

Conclusion: Our data give an update on the disease course of generalized MG in the new century. Diagnostic subgroups and response to treatment within the first 2 years help to predict the long term outcome.
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http://dx.doi.org/10.1212/WNL.0000000000010209DOI Listing
September 2020

Laboratory Tests for Neuropathies: What to do and to Avoid.

J Neuromuscul Dis 2020 ;7(3):279-286

Department of Neurology, Medical University Innsbruck, Austria.

Objectives: laboratory tests for work-up of hereditary and acquired neuropathies of peripheral nerves are frequently uncritically utilized. This overview focuses on the most common laboratory tests and investigations needed for diagnosing PNPs by the general neurologist.

Method: Literature search.

Results: laboratory tests recommended for the work-up of hereditary and acquired neuropathies should be chosen according to the individual and family history, clinical presentation, and electrophysiological findings. Laboratory tests should be selected specifically according to the suspected type of neuropathy to avoid unnecessary tests and expenses. Work-up should include as few samples as necessary for uncovering the etiology and should consider the sensitivity/specificity of the tests applied.. Basic screening tests for neuropathies should include a blood cell count, thyroid, renal and liver function tests, blood glucose levels, HbA1c, vitamin-B12, and immunofixation. Other laboratory investigations should be carried out only if a specific phenotype is present or if unexpected changes of the disease course occur. In these cases referral to a neuromuscular center is recommended.

Conclusions: Laboratory tests are helpful for the diagnosis of acquired and hereditary neuropathies but these tests should be ordered according to the history, clinical presentation and findings on electrophysiological investigations. If basic laboratory parameters fail to uncover the etiology, patients should be referred to a center specialized in neuromuscular disorders.
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http://dx.doi.org/10.3233/JND-200488DOI Listing
January 2020

Increased serum neurofilament light chain concentration indicates poor outcome in Guillain-Barré syndrome.

J Neuroinflammation 2020 Mar 17;17(1):86. Epub 2020 Mar 17.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Background: Guillain-Barré syndrome (GBS) is an autoimmune disease that results in demyelination and axonal damage. Five percent of patients die and 20% remain significantly disabled on recovery. Recovery is slow in most cases and eventual disability is difficult to predict, especially early in the disease. Blood or cerebrospinal fluid (CSF) biomarkers that could help identify patients at risk of poor outcome are required. We measured serum neurofilament light chain (sNfL) concentrations from blood taken upon admission and investigated a correlation between sNfL and clinical outcome.

Methods: Baseline sNfL levels in 27 GBS patients were compared with a control group of 22 patients with diagnoses not suggestive of any axonal damage. Clinical outcome parameters for GBS patients included (i) the Hughes Functional Score (HFS) at admission, nadir, and discharge; (ii) the number of days hospitalised; and (iii) whether intensive care was necessary.

Results: The median sNfL concentration in our GBS sample on admission was 85.5 pg/ml versus 9.1 pg/ml in controls. A twofold increase in sNfL concentration at baseline was associated with an HFS increase of 0.6 at nadir and reduced the likelihood of discharge with favourable outcome by a factor of almost three. Higher sNfL levels upon admission correlated well with hospitalisation time (r = 0.69, p < 0.0001), during which transfer to intensive care occurred more frequently at an odds ratio of 2.4. Patients with baseline sNfL levels below 85.5 pg/ml had a 93% chance of being discharged with an unimpaired walking ability.

Conclusions: sNfL levels measured at hospital admission correlated with clinical outcome in GBS patients. These results represent amounts of acute axonal damage and reflect mechanisms resulting in disability in GBS. Thus, sNfL may serve as a convenient blood-borne biomarker to personalise patient care by identifying those at higher risk of poor outcome.
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http://dx.doi.org/10.1186/s12974-020-01737-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079539PMC
March 2020

Frequency and clinical features of treatment-refractory myasthenia gravis.

J Neurol 2020 Apr 11;267(4):1004-1011. Epub 2019 Dec 11.

Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Background: To investigate the frequency and characterize the clinical features of treatment-refractory myasthenia gravis in an Austrian cohort.

Methods: Patient charts of 126 patients with generalized myasthenia gravis and onset between 2000 and 2016 were analyzed retrospectively. Patients were classified as treatment-refractory according to strict, predefined criteria. These mandated patients being at least moderately symptomatic (i.e., MGFA class III) or needing either maintenance immunoglobulins or plasma exchange therapy for at least 1 year in spite of two adequately dosed immunosuppressive drugs. Clinical features and outcome at last follow-up were compared to treatment-responsive patients.

Results: 14 out of 126 patients (11.1%) met these criteria of treatment-refractory myasthenia gravis. Treatment-refractory patients had more frequent clinical exacerbations and more often received rescue treatments or a further escalation of immunosuppressive therapies. They also remained more severely affected at last follow-up. An early onset of myasthenia gravis was associated with a higher risk for a refractory course.

Conclusion: A small subgroup of patients with generalized myasthenia gravis do not respond sufficiently to standard therapies. Refractory disease has considerable implications for both patients and health care providers and highlights an unmet need for new treatment options.
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http://dx.doi.org/10.1007/s00415-019-09667-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109164PMC
April 2020

High efficacy of rituximab for myasthenia gravis: a comprehensive nationwide study in Austria.

J Neurol 2019 Mar 16;266(3):699-706. Epub 2019 Jan 16.

Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.

Background: Most patients with myasthenia gravis (MG) need long-term immunosuppressive therapy. However, conventional agents may have intolerable side effects, take too long or fail to achieve disease control. Rituximab (RTX) has emerged as an off-label treatment for refractory MG, but data on its use are still sparse.

Methods: We conducted a retrospective nationwide study contacting all Austrian neurologists to provide anonymized data of all adult MG patients treated with RTX and minimum follow-up of 3 months. The Myasthenia Gravis Foundation of America Postintervention Status scale was used to assess outcomes.

Results: 34 (60.7%) of a total of 56 patients were women. Median (IQR) age at diagnosis of MG and start of RTX were 41.5 (24.3; 65.8) and 47.5 (33; 71) years, respectively. Antibodies (ab) against acetylcholine receptor (AchR) and muscle-specific tyrosine kinase (MuSK) were present in 69.6% and 25% of patients, respectively (seronegative: 5.4%). Before RTX, 47 (83.9%) patients had had plasma exchange, immune adsorption or immunoglobulins. Three months after RTX, 14 of 53 (26.4%) patients were in remission. At last follow-up after a median of 20 (10; 53) months, remission was present in 42.9% of patients and another 25% had minimal manifestations. Remission was more frequent in patients with MuSK ab vs. those with AchR ab (71.4% vs. 35.9%, p = 0.022). RTX was safe. The presence of MuSK ab independently predicted remission after RTX.

Conclusion: In this retrospective study on RTX for MG, the largest to date, RTX appeared safe, efficacious and fast acting. Benefit from RTX was greatest in MuSK ab + MG.
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http://dx.doi.org/10.1007/s00415-019-09191-6DOI Listing
March 2019

Multifocal motor neuropathy in Austria: a nationwide survey of clinical features and response to treatment.

J Neurol 2018 Dec 26;265(12):2834-2840. Epub 2018 Sep 26.

Department of Neurology, KH Wels-Grieskirchen, Wels, Austria.

Background And Objectives: Multifocal motor neuropathy (MMN) is a rare neuropathy and detailed descriptions of larger patient cohorts are scarce. The objective of this study was to evaluate epidemiological, clinical, and laboratory features of MMN patients and their response to treatment in Austria and to compare these data with those from the literature.

Methods: Anonymized demographic and clinical data about MMN patients until 31.12.2017 were collected from registered Austrian neurologists. Exploratory statistics on clinical and laboratory features as well as treatment regimens and responses were performed.

Results: 57 Patients with MMN were identified, resulting in a prevalence of 0.65/100.000. Mean age of onset was 44.1 ± 13.1 years, the diagnostic delay 5.5 ± 8.4 years. In 77% of patients, symptom onset was in the upper limbs, and in 92%, it occurred in distal muscles. Proximal onset was never observed in the lower limbs. At the final follow-up, the majority of patients had atrophy (88%) in affected regions. Definite motor conduction blocks (CB) were found in 54 patients. Anti-GM1-IgM antibodies were present in 43%. Treatment with intravenous immunoglobulins improved muscle strength and INCAT score initially, but at last follow-up, both scores deteriorated to values before treatment.

Discussion: The findings of the present study corroborate the previous findings in MMN. Onset typically occurs in the upper limbs and mostly distal, CBs are found in the majority of cases, while anti-GM1-IgM antibodies are detected in only approximately 40%. Our study underlines that the initial good response to treatment fades over time.
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http://dx.doi.org/10.1007/s00415-018-9071-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244652PMC
December 2018

Mutations outside the N-terminal part of RBCK1 may cause polyglucosan body myopathy with immunological dysfunction: expanding the genotype-phenotype spectrum.

J Neurol 2018 Feb 19;265(2):394-401. Epub 2017 Dec 19.

Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

A subset of patients with polyglucosan body myopathy was found to have underlying mutations in the RBCK1 gene. Affected patients may display diverse symptoms ranging from skeletal muscular weakness, cardiomyopathy to chronic autoinflammation and immunodeficiency. It was suggested that the exact localization of the mutation within the gene might be responsible for the specific phenotype, with N-terminal mutations causing severe immunological dysfunction and mutations in the middle or C-terminal part leading to a myopathy phenotype. We report the clinical, immunological and genetic findings of two unrelated individuals suffering from a childhood-onset RBCK1-asscociated disease caused by the same homozygous truncating mutation (NM_031229.2:c.896_899del, p.Glu299Valfs*46) in the middle part of the RBCK1 gene. Our patients suffered from a myopathy with cardiac involvement, but in contrast to previous reports on mutations in this part of the gene, also displayed signs of autoinflammation and immunodeficiency. Our report suggests that RBCK1 mutations at locations that were previously thought to lack immunological features may also present with immunological dysfunction later in the disease course. This notably broadens the genotype-phenotype correlation of RBCK1-related polyglucosan body myopathy.
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http://dx.doi.org/10.1007/s00415-017-8710-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808061PMC
February 2018

Iodinated contrast agents in patients with myasthenia gravis: a retrospective cohort study.

J Neurol 2017 Jun 26;264(6):1209-1217. Epub 2017 May 26.

Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Currently, it has not been satisfactorily established, whether modern low-osmolality iodinated contrast agents (ICAs) used in computed tomography (CT) studies are a risk factor for exacerbation of myasthenic symptoms. The rate of acute adverse events as well as delayed clinical worsening up to 30 days were analyzed in 73 patients with confirmed myasthenia gravis (MG) who underwent contrast-enhanced CT studies and compared to 52 patients who underwent unenhanced CT studies. One acute adverse event was documented. 12.3% of MG patients experienced a delayed exacerbation of symptoms after ICA administration. The rate of delayed severe exacerbation was higher in the contrast-enhanced group. Alternative causes for the exacerbation of MG-related symptoms were more likely than ICA administration in all cases. ICA administration for CT studies in MG patients should not be withheld if indicated, but patients particularly those with concomitant acute diseases should be carefully monitored for exacerbation of symptoms.
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http://dx.doi.org/10.1007/s00415-017-8518-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486553PMC
June 2017

Between- and within-site variability of fMRI localizations.

Hum Brain Mapp 2016 06 9;37(6):2151-60. Epub 2016 Mar 9.

Department of Neurology and MR Center of Excellence, Medical University of Vienna, Austria.

This study provides first data about the spatial variability of fMRI sensorimotor localizations when investigating the same subjects at different fMRI sites. Results are comparable to a previous patient study. We found a median between-site variability of about 6 mm independent of task (motor or sensory) and experimental standardization (high or low). An intraclass correlation coefficient analysis using data quality measures indicated a major influence of the fMRI site on variability. In accordance with this, within-site localization variability was considerably lower (about 3 mm). We conclude that the fMRI site is a considerable confound for localization of brain activity. However, when performed by experienced clinical fMRI experts, brain pathology does not seem to have a relevant impact on the reliability of fMRI localizations. Hum Brain Mapp 37:2151-2160, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/hbm.23162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867524PMC
June 2016

Early dysfunctions of fronto-parietal praxis networks in Parkinson's disease.

Brain Imaging Behav 2017 04;11(2):512-525

Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria.

In Parkinson's disease (PD) the prevalence of apraxia increases with disease severity implying that patients in early stages may already have subclinical deficits. The aim of this exploratory fMRI study was to investigate if subclinical aberrations of the praxis network are already present in patients with early PD. In previous functional imaging literature only data on basal motor functions in PD exists. Thirteen patients with mild parkinsonian symptoms and without clinically diagnosed apraxia and 14 healthy controls entered this study. During fMRI participants performed a pantomime task in which they imitated the use of visually presented objects. Patients were measured ON and OFF dopaminergic therapy to evaluate a potential medication effect on praxis abilities and related brain functions. Although none of the patients was apraxic according to De Renzi ideomotor scores (range 62-72), patients OFF showed significantly lower praxis scores than controls. Patients exhibited significant hyperactivation in left fronto-parietal core areas of the praxis network. Frontal activations were clearly dominant in patients and were correlated with lower individual praxis scores. We conclude that early PD patients already show characteristic signs of praxis network dysfunctions and rely on specific hyperactivations to avoid clinically evident apraxic symptoms. Subclinical apraxic deficits were shown to correlate with an activation shift from left parietal to left frontal areas implying a prospective individual imaging marker for incipient apraxia.
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http://dx.doi.org/10.1007/s11682-016-9532-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408054PMC
April 2017

Associations between co-medications and survival in ALS-a cohort study from Austria.

J Neurol 2015 Jul 10;262(7):1698-705. Epub 2015 May 10.

Department of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria,

The aim of this study was to evaluate associations between co-medications and survival of patients with amyotrophic lateral sclerosis (ALS). Prescription databases of the Austrian sickness funds covering more than 5 million people formed the basis of this study. ALS cases were deduced from riluzole prescriptions during the study period from January 1, 2008, to June 30, 2012. After adjusting for potential confounding factors associations between co-medications and ALS survival were analyzed. A total of 522 ALS patients could be identified during the study period. Sixteen of the most frequently used drug classes were considered for the survival analyses of which two were nominally associated with ALS survival. Proton pump inhibitors (PPI) were negatively correlated with survival (HR 1.34, 95 % CI 1.04-1.73) and centrally acting muscle relaxants (CAMR) showed a positive association (HR 0.56, 95 % CI 0.39-0.81). After correcting for multiple testing, the association between CAMR and ALS survival remained significant (p = 0.03). In conclusion, this is the first study systematically evaluating potential associations between commonly used drugs and ALS disease course. We report a positive association between CAMR use and survival, which may have derived from an indication bias representing the better prognosis of the upper motor neuron predominant disease variant. However, this is still interesting since it demonstrates the sensitivity of our study design to pick up survival effects. The use of large prescription registries could thus provide a valuable basis to find clues to underlying pathophysiological mechanisms in ALS.
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http://dx.doi.org/10.1007/s00415-015-7767-7DOI Listing
July 2015

Finger dexterity deficits in Parkinson's disease and somatosensory cortical dysfunction.

Parkinsonism Relat Disord 2015 Mar 5;21(3):259-65. Epub 2015 Jan 5.

Department of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria; MR Center of Excellence, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria. Electronic address:

Introduction: The patho-physiological basis for finger dexterity deficits in Parkinson's disease (PD) is controversial. Previously, bradykinesia was regarded as the major mechanism. However, recent research suggested limb-kinetic apraxia as an important component of impaired fine motor skills in PD. In contrast to bradykinesia, limb-kinetic apraxia only marginally responds to dopaminergic treatment. Here we investigate the novel hypothesis that the dexterity deficits are related to an intrinsic dysfunction of primary somatosensory cortex (S1), which is not reversible by dopaminergic medication.

Methods: Applying a standard and approved dexterity task (coin rotation), brain activation networks were investigated using functional magnetic resonance imaging in PD patients both ON and OFF medication and matched healthy controls.

Results: PD patients both ON and OFF medication showed impaired S1 activation relative to controls (p < 0.05; region of interest based analysis). The impaired S1 activation remained unchanged by dopaminergic medication. Despite the considerable clinical deficit, no other brain area showed impaired activation. In contrast, structures of the basal ganglia--motor cortex loop responded to dopaminergic medication. Behaviorally, dexterity performance both ON and OFF was significantly (p < 0.05) reduced relative to controls.

Conclusions: Our results provide first evidence that dexterity deficits in PD are related to an S1 dysfunction which is insensitive to dopaminergic treatment.
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http://dx.doi.org/10.1016/j.parkreldis.2014.12.025DOI Listing
March 2015

Epidemiology of amyotrophic lateral sclerosis and effect of riluzole on disease course.

Neuroepidemiology 2015 7;44(1):6-15. Epub 2015 Jan 7.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Objectives: To assess the epidemiology of ALS in Austria and to evaluate the long-term effect of riluzole treatment on survival.

Methods: Hospital discharge and riluzole prescription databases were used to identify ALS cases from January 2008 to June 2012. Using the capture-recapture method we evaluated the incidence and prevalence of ALS and patients' survival in dependence of age, gender and riluzole treatment.

Results: The corrected incidence and prevalence of ALS were 3.13/100,000 person-years (95% CI, 2.77 to 3.50) and 9.14/100,000 persons (95% CI, 8.53 to 9.79), respectively. Median survival from diagnosis was 676 days (95% CI, 591 to 761). A younger age at diagnosis was associated with a longer survival. Gender did not appear to affect survival time. Riluzole therapy was associated with a survival advantage only for the initial treatment period. The adjusted hazard ratio of mortality for using riluzole increased continually over time resulting in an apparent reversal of its beneficial effect after 6 months of therapy.

Conclusions: We report incidence and prevalence estimates that are on the upper end of the wide range discussed in literature. Riluzole seems to exert a beneficial effect only in the first 6 months of therapy.
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http://dx.doi.org/10.1159/000369813DOI Listing
January 2016

Comparing the Microvascular Specificity of the 3- and 7-T BOLD Response Using ICA and Susceptibility-Weighted Imaging.

Front Hum Neurosci 2013 9;7:474. Epub 2013 Aug 9.

Study Group Clinical fMRI, Department of Neurology, Medical University of Vienna , Vienna , Austria ; High Field Magnetic Resonance Imaging Center of Excellence, Medical University of Vienna , Vienna , Austria.

In functional MRI it is desirable for the blood-oxygenation level dependent (BOLD) signal to be localized to the tissue containing activated neurons rather than the veins draining that tissue. This study addresses the dependence of the specificity of the BOLD signal - the relative contribution of the BOLD signal arising from tissue compared to venous vessels - on magnetic field strength. To date, studies of specificity have been based on models or indirect measures of BOLD sensitivity such as signal to noise ratio and relaxation rates, and assessment has been made in isolated vein and tissue voxels. The consensus has been that ultra-high field systems not only significantly increase BOLD sensitivity but also specificity, that is, there is a proportionately reduced signal contribution from draining veins. Specificity was not quantified in prior studies, however, due to the difficulty of establishing a reliable network of veins in the activated volume. In this study we use a map of venous vessel networks extracted from 7 T high resolution Susceptibility-Weighted Images to quantify the relative contributions of micro- and macro-vasculature to functional MRI results obtained at 3 and 7 T. High resolution measurements made here minimize the contribution of physiological noise and Independent Component Analysis (ICA) is used to separate activation from technical, physiological, and motion artifacts. ICA also avoids the possibility of timing-dependent bias from different micro- and macro-vasculature responses. We find a significant increase in the number of activated voxels at 7 T in both the veins and the microvasculature - a BOLD sensitivity increase - with the increase in the microvasculature being higher. However, the small increase in sensitivity at 7 T was not significant. For the experimental conditions of this study, our findings do not support the hypothesis of an increased specificity of the BOLD response at ultra-high field.
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http://dx.doi.org/10.3389/fnhum.2013.00474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739379PMC
August 2013

Variability of clinical functional MR imaging results: a multicenter study.

Radiology 2013 Aug 22;268(2):521-31. Epub 2013 Mar 22.

Department of Neurology, MR Center of Excellence, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.

Purpose: To investigate intersite variability of clinical functional magnetic resonance (MR) imaging, including influence of task standardization on variability and use of various parameters to inform the clinician whether the reliability of a given functional localization is high or low.

Materials And Methods: Local ethics committees approved the study; all participants gave written informed consent. Eight women and seven men (mean age, 40 years) were prospectively investigated at three experienced functional MR sites with 1.5- (two sites) or 3-T (one site) MR. Nonstandardized motor and highly standardized somatosensory versions of a frequently requested clinical task (localization of the primary sensorimotor cortex) were used. Perirolandic functional MR variability was assessed (peak activation variability, center of mass [COM] variability, intraclass correlation values, overlap ratio [OR], activation size ratio). Data quality measures for functional MR images included percentage signal change (PSC), contrast-to-noise ratio (CNR), and head motion parameters. Data were analyzed with analysis of variance and a correlation analysis.

Results: Localization of perirolandic functional MR activity differed by 8 mm (peak activity) and 6 mm (COM activity) among sites. Peak activation varied up to 16.5 mm (COM range, 0.4-16.5 mm) and 45.5 mm (peak activity range, 1.8-45.5 mm). Signal strength (PSC, CNR) was significantly lower for the somatosensory task (mean PSC, 1.0% ± 0.5 [standard deviation]; mean CNR, 1.2 ± 0.4) than for the motor task (mean PSC, 2.4% ± 0.8; mean CNR, 2.9 ± 0.9) (P < .001, both). Intersite variability was larger with low signal strength (negative correlations between signal strength and peak activation variability) even if the task was highly standardized (mean OR, 22.0% ± 18.9 [somatosensory task] and 50.1% ± 18.8 [motor task]).

Conclusion: Clinical practice and clinical functional MR biomarker studies should consider that the center of task-specific brain activation may vary up to 16.5 mm, with the investigating site, and should maximize functional MR signal strength and evaluate reliability of local results with PSC and CNR.
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http://dx.doi.org/10.1148/radiol.13121357DOI Listing
August 2013

New type of cortical neuroplasticity after nerve repair in brachial plexus lesions.

Arch Neurol 2011 Nov;68(11):1467-70

Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.

Background: In brachial plexus avulsion, a recent technique connects the ending of the disrupted musculocutaneous nerve to the side of the intact phrenic nerve to regain elbow flexion. This requires the phrenic nerve to perform a new double function: independent control of breathing and elbow flexion. Neuroplastic changes associated with acquisition of double nerve functions have not yet been investigated.

Objective: To evaluate neuroplastic changes associated with acquisition of double nerve functions in a monofunctional nerve (phrenic nerve).

Design: Clinical and functional magnetic resonance imaging investigations during arm movements, forced inspiration, and motor control tasks.

Setting: Investigations at the Medical University of Vienna, Vienna, Austria.

Participants: Three healthy control subjects, 2 patients with phrenic nerve end-to-side coaptation, and 1 control patient with C7 end-to-end coaptation (same clinical presentation but phrenic nerve unchanged).

Results: Clinical documentation showed that both patients with phrenic nerve end-to-side coaptation were able to control the diaphragm and the biceps independently via the same phrenic nerve. In contrast to all controls, both patients with phrenic nerve end-to-side coaptation activated the cortical diaphragm areas with flexion of the diseased arm.

Conclusion: Our functional magnetic resonance imaging data indicate that the patient's cortical diaphragm areas reorganize in such a way that independent control of breathing and elbow flexion is possible with the same neuronal population.
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http://dx.doi.org/10.1001/archneurol.2011.596DOI Listing
November 2011

An fMRI marker for peripheral nerve regeneration.

Neurorehabil Neural Repair 2011 Jul-Aug;25(6):577-9. Epub 2011 Mar 24.

Medical University of Vienna, Vienna, Austria.

Final outcome after surgical repair of peripheral nerve transections varies. Here, we present the first longitudinal functional magnetic resonance imaging (fMRI) observation of cortical somatosensory reorganization patterns after surgery. A 43-year-old man presented with isolated complete transection of the right median nerve and underwent immediate epineural end-to-end coaptation. Applying standardized vibrotactile median nerve stimulation, 3 T brain activation maps were evaluated at 1, 7, 15 weeks and 1 year after surgery. Initially, the affected hemisphere showed no primary activation but increased frontoparietal activity. After 1 year, primary activation had recovered, and frontoparietal activity was decreased relative to the nonaffected hemisphere. Based on these longitudinal fMRI patterns, we propose a new marker for restoration of somatosensory function, which may not be provided by electrophysiological methods.
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http://dx.doi.org/10.1177/1545968310397552DOI Listing
May 2012

How much are clinical fMRI reports influenced by standard postprocessing methods? An investigation of normalization and region of interest effects in the medial temporal lobe.

Hum Brain Mapp 2010 Dec 4;31(12):1951-66. Epub 2010 Mar 4.

Study Group Clinical fMRI, Department of Neurology, Medical University of Vienna, Vienna, Austria.

Recent evidence has indicated that standard postprocessing methods such as template-based region of interest (ROI) definition and normalization of individual brains to a standard template may influence final outcome of functional magnetic resonance imaging investigations. Here, we provide the first comprehensive investigation into whether ROI definition and normalization may also change the clinical interpretation of patient data. A series of medial temporal lobe epilepsy patients were investigated with a clinical memory paradigm and individually delineated as well as template-based ROIs. Different metrics for activation quantification were applied. Results show that the application of template-based ROIs can significantly change the clinical interpretation of individual patient data. This relates to sensitivity for brain activation and hemispheric dominance. We conclude that individual ROIs should be defined on nontransformed functional data and that use of more than one metric for activation quantification is beneficial.
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http://dx.doi.org/10.1002/hbm.20990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6870663PMC
December 2010

A population-specific symmetric phase model to automatically analyze susceptibility-weighted imaging (SWI) phase shifts and phase symmetry in the human brain.

J Magn Reson Imaging 2010 Jan;31(1):215-20

Department of Radiology, Medical University of Vienna, Vienna, Austria.

Purpose: To create a population-specific symmetric phase model and to evaluate the susceptibility-weighted imaging (SWI) phase in terms of phase shift using different segmentation methods (manual and automatic) and phase shift symmetry, which is expected as a marker for lateralized Parkinson's disease (PD) symptoms.

Materials And Methods: SWI and T(1)-weighted data from 25 PD patients and five healthy controls were acquired on a 3T MRI system. A population-specific, symmetric phase model was developed. Regions of interest (ROIs) were defined manually on the phase model, manually on each individual data set, and automatically using model-based segmentation (MBS). Manually- and MBS-defined ROIs were compared using kappa values, and left-right phase symmetry was evaluated using correlation analysis.

Results: Independent of the analysis method, a phase increase from the anterior to the posterior putamen, and the average phase value relationship substantia nigra > globus pallidus > red nucleus was found. Phase symmetry analysis shows a difference between lateralized and symmetric PD.

Conclusion: The symmetric phase model helps to analyze phase data with similar accuracy, but a greatly reduced tracing effort compared to individual tracing and also allows evaluating left-right phase symmetries.
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http://dx.doi.org/10.1002/jmri.22013DOI Listing
January 2010

Evaluation of functional cortex for the diseased hand in a patient after hemispherectomy.

Arch Neurol 2008 Dec;65(12):1664-5

Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.

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http://dx.doi.org/10.1001/archneur.65.12.1664DOI Listing
December 2008