TY  - JOUR
AU  - Oertel, W.H.
AU  - Henrich, M.T.*
AU  - Bergquist, F.*
AU  - Janzen, A.*
AU  - Geibl, F.F.*
AU  - Strupp, M.*
C1  - 74980
C2  - 57681
TI  - "How to save a marriage": Treatment of REM sleep behavior disorder (RBD) with acetyl-leucine in a patient with Parkinson's disease.
JO  - J. Neurol.
VL  - 272
IS  - 7
PY  - 2025
SN  - 0340-5354
ER  - 

TY  - JOUR
AU  - Indelicato, E.
AU  - Schlieben, L.D.
AU  - Stenton, S.L.*
AU  - Boesch, S.*
AU  - Škorvánek, M.*
AU  - Necpál, J.*
AU  - Jech, R.*
AU  - Winkelmann, J.
AU  - Prokisch, H.
AU  - Zech, M.
C1  - 70725
C2  - 55676
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
TI  - Dystonia and mitochondrial disease: The movement disorder connection revisited in 900 genetically diagnosed patients.
JO  - J. Neurol.
PB  - Springer Heidelberg
PY  - 2024
SN  - 0340-5354
ER  - 

TY  - JOUR
AB  - BACKGROUND: Heterozygous loss-of-function variants in CHD8 have been associated with a syndromic neurodevelopmental-disease spectrum, collectively referred to as CHD8-related neurodevelopmental disorders. Several different clinical manifestations, affecting neurodevelopmental and systemic domains, have been described, presenting with highly variable expressivity. Some expressions are well established and comprise autism spectrum disorders, psychomotor delay with cognitive impairment, postnatal overgrowth with macrocephaly, structural brain abnormalities, gastrointestinal disturbances, and behavioral and sleep-pattern problems. However, the complete phenotypic spectrum of CHD8-related disorders is still undefined. In 2021, our group described two singular female patients with CHD8-related neurodevelopmental disorder and striking dystonic manifestations, prompting the suggestion that dystonia should be considered a possible component of this condition. CASE SERIES PRESENTATION: We describe three additional unrelated female individuals, each carrying a different CHD8 frameshift variant and whose clinical presentations were primarily characterized by young-onset dystonia. Their dystonic manifestations were remarkably heterogeneous and ranged from focal, exercise-dependent, apparently isolated forms to generalized permanent phenotypes accompanied by spasticity and tremor. Neurocognitive impairment and autistic behaviors, typical of CHD8-related disorders, were virtually absent or at the mild end of the spectrum. CONCLUSIONS: This work validates our previous observation that dystonia is part of the phenotypic spectrum of CHD8-related neurodevelopmental disorders with potential female preponderance, raising new challenges and opportunities in the diagnosis and management of this condition. It also highlights the importance of in-depth neurologic phenotyping of patients carrying variants associated with neurodevelopmental disorders, as the connection between neurodevelopmental and movement disorders is proving closer than previously appreciated.
AU  - Sorrentino, U.
AU  - Boesch, S.*
AU  - Doummar, D.*
AU  - Ravelli, C.*
AU  - Serranová, T.*
AU  - Indelicato, E.*
AU  - Winkelmann, J.
AU  - Burglen, L.*
AU  - Jech, R.*
AU  - Zech, M.
C1  - 70188
C2  - 55449
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
SP  - 2859-2865
TI  - CHD8-related disorders redefined: An expanding spectrum of dystonic phenotypes.
JO  - J. Neurol.
VL  - 271
IS  - 5
PB  - Springer Heidelberg
PY  - 2024
SN  - 0340-5354
ER  - 

TY  - JOUR
AB  - Background: Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by genetic defects resulting in impaired neuromuscular transmission. Although effective treatments are available, CMS is probably underdiagnosed, and systematic clinico-genetic investigations are warranted. Methods: We used a nationwide approach to collect Austrian patients with genetically confirmed CMS. We provide a clinical and molecular characterization of this cohort and aimed to ascertain the current frequency of CMS in Austria. Results: Twenty-eight cases with genetically confirmed CMS were identified, corresponding to an overall prevalence of 3.1 per million (95% CI 2.0–4.3) in Austria. The most frequent genetic etiology was CHRNE (n = 13), accounting for 46.4% of the cohort. Within this subgroup, the variant c.1327del, p.(Glu443Lysfs*64) was detected in nine individuals. Moreover, causative variants were found in DOK7 (n = 4), RAPSN (n = 3), COLQ (n = 2), GMPPB (n = 2), CHAT (n = 1), COL13A1 (n = 1), MUSK (n = 1) and AGRN (n = 1). Clinical onset within the first year of life was reported in one half of the patients. Across all subtypes, the most common symptoms were ptosis (85.7%), lower limb (67.9%), upper limb (60.7%) and facial weakness (60.7%). The majority of patients (96.4%) received specific treatment, including acetylcholinesterase inhibitors in 20, adrenergic agonists in 11 and 3,4-diaminopyridine in nine patients. Conclusions: Our study presents the first systematic characterization of individuals with CMS in Austria, providing prevalence estimates and genotype–phenotype correlations that may help to improve the diagnostic approach and patient management.
AU  - Krenn, M.*
AU  - Sener, M.*
AU  - Rath, J.*
AU  - Zulehner, G.*
AU  - Keritam, O.*
AU  - Wagner, M.
AU  - Laccone, F.*
AU  - Iglseder, S.*
AU  - Marte, S.*
AU  - Baumgartner, M.*
AU  - Eisenkölbl, A.*
AU  - Liechtenstein, C.*
AU  - Rudnik, S.*
AU  - Quasthoff, S.*
AU  - Grinzinger, S.*
AU  - Spenger, J.*
AU  - Wortmann, S.B.*
AU  - Löscher, W.N.*
AU  - Zimprich, F.*
AU  - Kellersmann, A.*
AU  - Rappold, M.*
AU  - Bernert, G.*
AU  - Freilinger, M.*
AU  - Cetin, H.*
C1  - 66553
C2  - 53215
SP  - 909-916
TI  - The clinical and molecular landscape of congenital myasthenic syndromes in Austria: A nationwide study.
JO  - J. Neurol.
VL  - 270
IS  - 2
PY  - 2023
SN  - 0340-5354
ER  - 

TY  - JOUR
AB  - BACKGROUND: Neuromuscular disorders (NMDs) are heterogeneous conditions with a considerable fraction attributed to monogenic defects. Despite the advancements in genomic medicine, many patients remain without a diagnosis. Here, we investigate whether a comprehensive reassessment strategy improves the diagnostic outcomes. METHODS: We analyzed 263 patients with NMD phenotypes that underwent diagnostic exome or genome sequencing at our tertiary referral center between 2015 and 2023. We applied a comprehensive reassessment encompassing variant reclassification, re-phenotyping and NGS data reanalysis. Multivariable logistic regression was performed to identify predictive factors associated with a molecular diagnosis. RESULTS: Initially, a molecular diagnosis was identified in 53 cases (20%), while an additional 23 (9%) had findings of uncertain significance. Following comprehensive reassessment, the diagnostic yield increased to 23%, revealing 44 distinct monogenic etiologies. Reasons for newly obtained molecular diagnoses were variant reclassifications in 7 and NGS data reanalysis in 3 cases including one recently described disease-gene association (DNAJB4). Male sex reduced the odds of receiving a molecular diagnosis (OR 0.42; 95%CI 0.21-0.82), while a positive family history (OR 5.46; 95%CI 2.60-11.76) and a myopathy phenotype (OR 2.72; 95%CI 1.11-7.14) increased the likelihood. 7% were resolved through targeted genetic testing or classified as acquired etiologies. CONCLUSION: Our findings reinforce the use of NGS in NMDs of suspected monogenic origin. We show that a comprehensive reassessment enhances diagnostic accuracy. However, one needs to be aware that genetic diagnoses are often made with uncertainty and can even be downgraded based on new evidence.
AU  - Krenn, M.*
AU  - Wagner, M.
AU  - Zulehner, G.*
AU  - Weng, R.*
AU  - Jäger, F.*
AU  - Keritam, O.*
AU  - Sener, M.*
AU  - Brücke, C.*
AU  - Milenkovic, I.*
AU  - Langer, A.*
AU  - Buchinger, D.*
AU  - Habersam, R.*
AU  - Mayerhanser, K.*
AU  - Brugger, M.*
AU  - Brunet, T.*
AU  - Jacob, M.*
AU  - Graf, E.*
AU  - Berutti, R.
AU  - Cetin, H.*
AU  - Hoefele, J.*
AU  - Winkelmann, J.
AU  - Zimprich, F.*
AU  - Rath, J.*
C1  - 69052
C2  - 53830
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
TI  - Next-generation sequencing and comprehensive data reassessment in 263 adult patients with neuromuscular disorders: Insights into the gray zone of molecular diagnoses.
JO  - J. Neurol.
PB  - Springer Heidelberg
PY  - 2023
SN  - 0340-5354
ER  - 

TY  - JOUR
AB  - Collagen XIII is a non-fibrillar transmembrane collagen which has been long recognized for its critical role in synaptic maturation of the neuromuscular junction. More recently, biallelic COL13A1 loss-of-function mutations were identified in three patients with congenital myasthenic syndrome (CMS), a rare inherited condition with defective neuromuscular transmission, causing abnormal fatigability and fluctuating muscle weakness and often successfully treated with acetylcholinesterase inhibitors. Here we report six additional CMS patients from three unrelated families with previously unreported homozygous COL13A1 loss-of-function mutations (p.Tyr216*, p.Glu543fs and p.Thr629fs). The phenotype of our cases was similar to the previously reported patients including respiratory distress and severe dysphagia at birth that often resolved or improved in the first days or weeks of life. All individuals had prominent eyelid ptosis with only minor ophthalmoparesis as well as generalized muscle weakness, predominantly affecting facial, bulbar, respiratory and axial muscles. Response to acetylcholinesterase inhibitor treatment was generally negative while salbutamol proved beneficial. Our data further support the causality of COL13A1 variants for CMS and suggest that this type of CMS might be clinically homogenous and requires alternative pharmacological therapy.
AU  - Dusl, M.*
AU  - Moreno, T.*
AU  - Munell, F.*
AU  - Macaya, A.*
AU  - Gratacòs, M.*
AU  - Abicht, A.*
AU  - Strom, T.M.
AU  - Lochmüller, H.*
AU  - Senderek, J.*
C1  - 55556
C2  - 46236
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
SP  - 1107-1112
TI  - Congenital myasthenic syndrome caused by novel COL13A1 mutations.
JO  - J. Neurol.
VL  - 266
IS  - 5
PB  - Springer Heidelberg
PY  - 2019
SN  - 0340-5354
ER  - 

TY  - JOUR
AB  - Introduction Treatment with botulinum toxin A is the evidence-based first-line therapy of cervical dystonia. The aim of this study was to analyze long-term data of the most commonly used products concerning safety and efficacy in a big cohort over decades.Methods We retrospectively analyzed the treatment data of all cervical dystonia patients in our outpatient clinic having at least three treatment sessions with current onabotulinumtoxinA or abobotulinumtoxinA. The observation period was up to 17 years for onabotulinumtoxinA and 27 years for abobotulinumtoxinA. We report on safety and efficacy, comparing parameters such as dose, treatment intervals, side effects, occurrence and reasons of primary or secondary non-response.Results We analyzed a total of 2592 and 6660 treatment sessions in 135 patients with onabotulinumtoxinA, 209 with abobotulinumtoxinA and 10 having received both preparations. We found a moderate increase of dosage in the first years which was succeeded by a stable mean dose (138 and 663 mouse units, respectively) and stable injection intervals from the beginning. The most frequent side effects were mild dysphagia (2/6%), muscle weakness (2/6%) and pain (2/2%). Reasons for therapy discontinuation were change to a nearby doctor, age, other diseases, spontaneous improvement, side effects or possible treatment failure. Of all patients, only two tested positive for neutralizing antibodies against botulinum toxin A.Conclusion We show that treatment of cervical dystonia with the two most frequently used botulinum toxin A preparations is a safe and effective therapy even over a long treatment duration of up to 27 years.
AU  - Jochim, A.*
AU  - Meindl, T.*
AU  - Mantel, T.*
AU  - Zwirner, S.*
AU  - Zech, M.
AU  - Castrop, F.*
AU  - Haslinger, B.*
C1  - 55970
C2  - 46733
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
SP  - 1879-1886
TI  - Treatment of cervical dystonia with abo- and onabotulinumtoxinA: Long-term safety and efficacy in daily clinical practice.
JO  - J. Neurol.
VL  - 266
IS  - 8
PB  - Springer Heidelberg
PY  - 2019
SN  - 0340-5354
ER  - 

TY  - JOUR
AB  - Objectives Vertigo is a common reason for primary care consultations, and its diagnosis and treatment consume considerable medical resources. However, limited information on the specific cost of vertigo is currently available. The aim of this study is to analyse the health care costs of vertigo and examine which individual characteristics would affect these costs. Study design We used cross-sectional data from the German KORA ("Cooperative Health Research in the Augsburg Region") FF4 study in 2013. Methods Impact of personal characteristics and other factors was modelled using a two-part model. Information on health care utilisation was collected by self-report. Results We included 2277 participants with a mean age of 60.8 (SD = 12.4), 48.4% male. Moderate or severe vertigo was reported by 570 (25.0%) participants. People with vertigo spent 818 Euro more than people without vertigo in the last 12 months (2720.9 Euro to 1902.9 Euro, SD = 4873.3 and 5944.1, respectively). Consultation costs at primary care physicians accounted for the largest increase in total health care costs with 177.2 Euro (p < 0.01). After adjusting for covariates, the presence of vertigo increased both the probability of having any health care costs (OR = 1.6, 95% CI =[1.2;2.4]) and the amount of costs (exp(beta) = 1.3, 95% CI = [1.1;1.5]). The analysis of determinants of vertigo showed that private insurance and a medium level of education decreased the probability of any costs, while higher income increased it. Conclusions The presence of vertigo and dizziness required considerable health care resources and created significantly more related costs in different health care sectors for both primary and pertinent secondary care.
AU  - Wang, X.*
AU  - Strobl, R.*
AU  - Holle, R.
AU  - Seidl, H.
AU  - Peters, A.
AU  - Grill, E.*
C1  - 56134
C2  - 46844
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
SP  - 2120-2128
TI  - Vertigo and dizziness cause considerable more health care resource use and costs: Results from the KORA FF4 study.
JO  - J. Neurol.
VL  - 266
IS  - 9
PB  - Springer Heidelberg
PY  - 2019
SN  - 0340-5354
ER  - 

TY  - JOUR
AB  - 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.
AU  - Krenn, M.*
AU  - Salzer, E.*
AU  - Simonitsch-Klupp, I.*
AU  - Rath, J.*
AU  - Wagner, M.
AU  - Haack, T.B.*
AU  - Strom, T.M.
AU  - Schänzer, A.*
AU  - Kilimann, M.W.*
AU  - Schmidt, R.L.J.*
AU  - Schmetterer, K.G.*
AU  - Zimprich, A.*
AU  - Boztug, K.*
AU  - Hahn, A.*
AU  - Zimprich, F.*
C1  - 52596
C2  - 44097
CY  - Heidelberg
SP  - 394–401
TI  - Mutations outside the N-terminal part of RBCK1 may cause polyglucosan body myopathy with immunological dysfunction: Expanding the genotype-phenotype spectrum.
JO  - J. Neurol.
VL  - 265
IS  - 2
PB  - Springer Heidelberg
PY  - 2018
SN  - 0340-5354
ER  - 

TY  - JOUR
AB  - The m.8344A>G mutation in the MTTK gene, which encodes the mitochondrial transfer RNA for lysine, is traditionally associated with myoclonic epilepsy and ragged-red fibres (MERRF), a multisystemic mitochondrial disease that is characterised by myoclonus, seizures, cerebellar ataxia, and mitochondrial myopathy with ragged-red fibres. We studied the clinical and paraclinical phenotype of 34 patients with the m.8344A>G mutation, mainly derived from the nationwide mitoREGISTER, the multicentric registry of the German network for mitochondrial disorders (mitoNET). Mean age at symptom onset was 24.5 years ±10.9 (6-48 years) with adult onset in 75 % of the patients. In our cohort, the canonical features seizures, myoclonus, cerebellar ataxia and ragged-red fibres that are traditionally associated with MERRF, occurred in only 61, 59, 70, and 63 % of the patients, respectively. In contrast, other features such as hearing impairment were even more frequently present (72 %). Other common features in our cohort were migraine (52 %), psychiatric disorders (54 %), respiratory dysfunction (45 %), gastrointestinal symptoms (38 %), dysarthria (36 %), and dysphagia (35 %). Brain MRI revealed cerebral and/or cerebellar atrophy in 43 % of our patients. There was no correlation between the heteroplasmy level in blood and age at onset or clinical phenotype. Our findings further broaden the clinical spectrum of the m.8344A>G mutation, document the large clinical variability between carriers of the same mutation, even within families and indicate an overlap of the phenotype with other mitochondrial DNA-associated syndromes.
AU  - Altmann, J.*
AU  - Büchner, B.*
AU  - Nadaj-Pakleza, A.*
AU  - Schäfer, J.*
AU  - Jackson, S.H.*
AU  - Lehmann, D.*
AU  - Deschauer, M.*
AU  - Kopajtich, R.
AU  - Lautenschläger, R.*
AU  - Kuhn, K.A.*
AU  - Karle, K.*
AU  - Schöls, L.*
AU  - Schulz, J.B.*
AU  - Weis, J.*
AU  - Prokisch, H.
AU  - Kornblum, C.*
AU  - Claeys, K.G.*
AU  - Klopstock, T.*
C1  - 48430
C2  - 41100
CY  - Heidelberg
SP  - 961-972
TI  - Expanded phenotypic spectrum of the m.8344A>G "MERRF" mutation: Data from the German mitoNET registry.
JO  - J. Neurol.
VL  - 263
IS  - 5
PB  - Springer Heidelberg
PY  - 2016
SN  - 0340-5354
ER  - 

TY  - JOUR
AB  - Inherited peripheral neuropathies (IPN) are one of the most frequent inherited causes of neurological disability characterized by considerable phenotypic and genetic heterogeneity. Based on clinical and electrophysiological properties, they can be subdivided into three main groups: HMSN, dHMN, and HSN. At present, more than 50 IPN genes have been identified. Still, many patients and families with IPN have not yet received a molecular genetic diagnosis because clinical genetic testing usually only covers a subset of IPN genes. Moreover, a considerable proportion of IPN genes has to be identified. Here we present results of WES in 27 IPN patients excluded for mutations in many known IPN genes. Eight of the patients received a definite diagnosis. While six of these patients carried bona fide pathogenic mutations in known IPN genes, two patients had mutations in genes known to be involved in other types of neuromuscular disorders. A further group of eight patients carried sequence variations in IPN genes that could not unequivocally be classified as pathogenic. In addition, combining data of WES and linkage analysis identified SH3BP4, ITPR3, and KLHL13 as novel IPN candidate genes. Moreover, there was evidence that particular mutations in PEX12, a gene known to cause Zellweger syndrome, could also lead to an IPN phenotype. We show that WES is a useful tool for diagnosing IPN and we suggest an expanded phenotypic spectrum of some genes involved in other neuromuscular and neurodegenerative disorders. Nevertheless, interpretation of variants in known and potential novel disease genes has remained challenging.
AU  - Schabhüttl, M.*
AU  - Wieland, T.
AU  - Senderek, J.*
AU  - Baets, J.*
AU  - Timmerman, V.*
AU  - de Jonghe, P.*
AU  - Reilly, M.M.*
AU  - Stieglbauer, K.*
AU  - Laich, E.*
AU  - Windhager, R.*
AU  - Erwa, W.*
AU  - Trajanoski, S.*
AU  - Strom, T.M.
AU  - Auer-Grumbach, M.*
C1  - 30805
C2  - 33972
CY  - Heidelberg
SP  - 970-982
TI  - Whole-exome sequencing in patients with inherited neuropathies: Outcome and challenges.
JO  - J. Neurol.
VL  - 261
IS  - 5
PB  - Springer Heidelberg
PY  - 2014
SN  - 0340-5354
ER  - 

TY  - JOUR
AB  - Mutations in C19orf12 have been recently identified as the molecular genetic cause of a subtype of neurodegeneration with brain iron accumulation (NBIA). Given the mitochondrial localization of the gene product the new NBIA subtype was designated mitochondrial membrane protein-associated neurodegeneration. Frequent features in the patients described so far included extrapyramidal signs and pyramidal tract involvement. Here, we report three C19orf12-mutant patients from two families presenting with predominant upper and lower motor neuron dysfunction mimicking amyotrophic lateral sclerosis with juvenile onset. While extrapyramidal signs were absent, all patients showed neuropsychological abnormalities with disinhibited or impulsive behavior. Optic atrophy was present in the simplex case. T2-weighted cranial MRI showed hypointensities suggestive of iron accumulation in the globi pallidi and the midbrain in all patients. Sequence analysis of C19orf12 revealed a novel mutation, p.Gly66del, compound heterozygous with known mutations in all patients. These patients highlight that C19orf12 defects should be considered as a differential diagnosis in patients with juvenile onset motor neuron diseases. Patients have to be examined carefully for neuropsychological abnormalities, optic neuropathy, and signs of brain iron accumulation in MRI.
AU  - Deschauer, M.*
AU  - Gaul, C.*
AU  - Behrmann, C.*
AU  - Prokisch, H.
AU  - Zierz, S.*
AU  - Haack, T.B.
C1  - 11109
C2  - 30524
SP  - 2434-2439
TI  - C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking juvenile amyotrophic lateral sclerosis
JO  - J. Neurol.
VL  - 259
IS  - 11
PB  - Springer
PY  - 2012
SN  - 0340-5354
ER  - 

TY  - JOUR
AB  - Nonmotor symptoms of Parkinson's disease can be as disabling as the much better studied motor symptoms. Among the nonmotor manifestations are numerous forms of alterations of physiologic sleep patterns that may present at different stages during the course of disease. These include changes believed to be primarily related to the underlying neurodegenerative process of the disease as well as those brought about secondarily, for example, by pharmacologic treatment. Also, sleep disturbances seen in Parkinson's disease can range from temporarily increased daytime sleepiness after introduction of a dopamine agonist to the therapeutic regime to specific sleep-related diagnoses such as restless legs syndrome, rapid eye movement sleep behavior disorder, periodic limb movements in sleep, and sleep-related breathing disorders such as obstructive sleep apnea. In this review, we discuss the different specific sleep disturbances that arise in the context of Parkinson's disease with a special emphasis on epidemiology, pathophysiology, and diagnosis.
AU  - Schulte, E.C.*
AU  - Winkelmann, J.
C1  - 5568
C2  - 28805
SP  - S328-S335
TI  - When Parkinson's disease patients go to sleep: Specific sleep disturbances related to Parkinson's disease.
JO  - J. Neurol.
VL  - 258
IS  - 2
PB  - Springer
PY  - 2011
SN  - 0340-5354
ER  - 

TY  - JOUR
AB  - Early pre-motor symptoms (also frequently termed "non-motor" symptoms) in Parkinson's disease (PD), which precede the onset of motor symptoms, are being increasingly recognized by clinicians. Non-motor symptoms in the pre-motor phase of PD include impaired olfaction (hyposmia), sleep disturbances (i.e., radid eye movement sleep behavior disorder, daytime sleepiness), behavioral/emotional dysfunction (i.e., change of personality or change of core personal characteristics), dysautonomia (i.e., constipation, urinary dysfunction, orthostatic hypotension), depressive symptoms (i.e., fatigue, apathy, anxiety), and chronic pain (joint and muscle). The pre-motor phase of PD is based on current pathophysiological concepts that relate these symptoms to early structural changes within lower brainstem nuclei and the peripheral nervous system including the autonomic and enteric ganglia. The perspective to identify these symptoms as early as possible will enable neurologists to make a diagnosis at the pre-motor stage of PD. Thus, the development of a PD risk score will be the first means to identify individuals at risk who are most likely to develop the prototypical motor symptoms of PD later in life. More importantly, these individuals at risk will be the first to benefit from disease-modifying strategies. In this workshop report, the elements of a PD risk score are proposed, including the stepwise sequence of escalating diagnostic measures to diagnose the pre-motor stage in PD.
AU  - Winkler, J.*
AU  - Ehret, R.*
AU  - Büttner, T.*
AU  - Dillmann, U.*
AU  - Fogel, W.*
AU  - Sabolek, M.*
AU  - Winkelmann, J.
AU  - Kassubek, J.*
C1  - 6498
C2  - 28809
SP  - S311-S315
TI  - Parkinson's disease risk score: Moving to a premotor diagnosis.
JO  - J. Neurol.
VL  - 258
PB  - Springer
PY  - 2011
SN  - 0340-5354
ER  - 

TY  - JOUR
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the selective death of motor neurons in the motor cortex, brain stem and spinal cord. Recently, missense variants in the angiogenin gene (ANG), an angiogenic factor expressed in ventral horn motor neurons that is up-regulated by hypoxia, have been found in ALS patients of Irish/Scottish, North American, Italian, French and Dutch descent. To investigate the role of ANG in the German population, we screened for mutations by sequencing the entire coding region of the ANG gene in a large sample of 581 German ALS cases and 616 sex- and age-matched healthy controls. We identified two heterozygous missense variants, F(-13)L and K54E, in two German sporadic ALS cases but not in controls. Both missense variants are novel and have not been previously found in ALS cases. Our results suggest that missense variants in the ANG gene play a role in ALS in the German population and provide further evidence to support the hypothesis that angiogenic factors up-regulated by hypoxia are involved in the pathophysiology of ALS.
AU  - Fernández-Santiago, R.*
AU  - Hoenig, S.*
AU  - Lichtner, P.
AU  - Sperfeld, AD.*
AU  - Sharma, M.*
AU  - Berg, D.*
AU  - Weichenrieder, O.*
AU  - Illig, T.
AU  - Eger, K.*
AU  - Meyer, T.*
AU  - Anneser, J.*
AU  - Münch, C.*
AU  - Zierz, S.*
AU  - Gasser, T.*
AU  - Ludolph, A.*
C1  - 1149
C2  - 26299
SP  - 1337-1342
TI  - Identification of novel Angiogenin (ANG) gene missense variants in German patients with amyotrophic lateral sclerosis.
JO  - J. Neurol.
VL  - 256
IS  - 8
PB  - Dietrich Steinkopff
PY  - 2009
SN  - 0340-5354
ER  - 

TY  - JOUR
AU  - Lücking, C.B.*
AU  - Lichtner, P.
AU  - Dichgans, M.*
AU  - Illig, T.
AU  - Gieger, C.
AU  - Berg, D.*
AU  - Gasser, T.*
C1  - 1986
C2  - 25283
SP  - 441-442
TI  - Polymorphisms in the proteasomal subunit alpha4 are not associated with Parkinson's disease.
JO  - J. Neurol.
VL  - 255
IS  - 3
PB  - Steinkopff
PY  - 2008
SN  - 0340-5354
ER  - 

TY  - JOUR
AB  - Homozygous mutations in the PINK1 gene have been shown to cause early-onset parkinsonism. Here, we describe a novel homozygous mutation (Q126P), identified in two affected German sisters with a clinical phenotype typical for PINK1-associated parkinsonism.We analysed lactate, pyruvate, carnitine and acylcarnitine blood levels, lactate levels under exercise and in the cerebrospinal fluid, activity of respiratory chain complexes I-IV in muscle biopsies and proteasomal activity in immortalized lymphoblasts, but found no evidence for mitochondrial or proteasomal dysfunction. MR spectroscopy revealed raised myoinositol levels in the basal ganglia of both patients, reflecting possible astroglial proliferation.
AU  - Prestel, J.*
AU  - Gempel, K.*
AU  - Hauser, T.K.*
AU  - Schweitzer, K.*
AU  - Prokisch, H.
AU  - Ahting, U.
AU  - Freudenstein, D.*
AU  - Bueltmann, E.*
AU  - Naegele, T.*
AU  - Berg, D.*
AU  - Klopstock, T.*
AU  - Gasser, T.*
C1  - 3764
C2  - 25622
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JO  - J. Neurol.
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IS  - 5
PB  - Springer
PY  - 2008
SN  - 0340-5354
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TY  - JOUR
AU  - Bax, R.
AU  - von Czettritz, G.
AU  - Eckardt, T.F.
AU  - Keidel, M.
AU  - Tirsch, W.S.
AU  - Weinmann, H.-M.
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SP  - S. 224
TI  - Amplitude Cycles in the EEG of Premature Infants During Quiet Sleep by Means of "Running" Frequency Analysis.
JO  - J. Neurol.
VL  - 239 (Suppl.2)
PY  - 1992
SN  - 0340-5354
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TY  - JOUR
AU  - Eckardt, T.
AU  - von Czettritz, G.
AU  - Bax, R.
AU  - Keidel, M.
AU  - Tirsch, W.S.
AU  - Weinmann, H.-M.
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C2  - 13417
SP  - S. 225
TI  - Simultaneous Changes of the Periodic Breathing Cycles Duration and the EEG Rhythmicity in Preterm Infants.
JO  - J. Neurol.
VL  - 239 (Suppl.2)
PY  - 1992
SN  - 0340-5354
ER  -