The stabilization effect of the conjoint tendon in reverse total shoulder arthroplasty.

BACKGROUND: Numerous factors determine stability of reverse total shoulder arthroplasty. The effect of the conjoint tendon in relation to stability remains unknown. In this biomechanical study, we evaluated the influence of the conjoint tendon on the anterior stability of reverse total shoulder arthroplasty with a hemispherical glenosphere and a glenosphere with 9 mm lateralisation. METHODS: A reverse total shoulder arthroplasty was implanted in 6 human cadaveric shoulders. The anterior stability was evaluated using a shoulder simulator. Two conditions, intact and dissected conjoint tendon, and 2 component configurations, a hemispherical glenosphere and a glenosphere with 9 mm lateralisation, were tested in each specimen. Testing of anterior stability was performed in 30° and 60° of abduction, with 0° and 30° of external rotation in the glenohumeral joint. FINDINGS: The conjoint tendon showed a significant influence on the anterior stability with a hemispherical glenosphere in 30° and 60° with neutral rotation (p = 0.028) as well as 30° abduction with 30° (p = 0.028) external rotation. The 9 mm lateralised glenosphere stabilized significantly reverse total shoulder arthroplasty with resected conjoint tendon compared to the hemispherical glenosphere with resected conjoint tendon (p = 0.028). INTERPRETATION: In a biomechanical setting the conjoint tendon has a stabilizing influence on the anterior stability of the reverse total shoulder arthroplasty with a hemispherical glenosphere in an abducted arm position, but this stabilizing effect was not seen with the lateralised glenosphere. The single influence of the lateralisation of the glenosphere on anterior stability was shown in cases of resected conjoint tendon.

Non-motor symptoms and quality of life in subjects with mild parkinsonian signs.

BACKGROUND: Mild parkinsonian signs (MPS) are frequent in the elderly population and associated with the presence of risk markers for Parkinson's disease (PD). Both MPS and non-motor signs may be present in prodromal PD and may significantly impair quality of life (QoL). OBJECTIVE: To disentangle the contribution of motor impairment and extra-motor manifestations to QoL in subjects with MPS (n=63), manifest PD (n=69), disorders with motor symptoms due to non-neurodegenerative diseases (n=213) and healthy controls (n=258). METHODS: Subjects with MPS, healthy controls, disease controls (patients with motor impairment due to, eg, arthrosis and spondylosis), and PD patients (total n=603) were selected from a large epidemiological longitudinal study, the EPIPARK cohort. Motor function was determined using the UPDRSIII protocol, and information on depressive symptoms, anxiety, sleep, and QoL was assessed via rating scales and data were analyzed. RESULTS: Depressive symptoms, anxiety, and sleep problems were equally frequent in the MPS group and controls. Health-related QoL was slightly reduced in the MPS group. Motor impairment and its extent was comparable between the MPS group and disease controls (UPDRSIII 5-6 points). Higher motor dysfunction was associated with lower QoL. Depressive symptoms, but not anxiety and daytime sleepiness, was significant predictors of general QoL, independent of motor function. CONCLUSIONS: Quality of life is slightly decreased in an elderly population with MPS. QoL is associated with severity of motor impairment but also with non-motor aspects, ie, depressive symptoms. Follow-up studies in large cohorts are warranted to determine the natural course of MPS and its impact on QoL.

Prediction of individual prosthesis size for valve-sparing aortic root reconstruction based on geometric features.

Valve-sparing aortic root reconstruction is an up- and-coming approach for patients suffering from aortic valve insufficiencies which promises to significantly reduce complications. However, the success of the treatment strongly depends on the challenging task of choosing the correct size of the prosthesis, for which, up to now, surgeons solely have to rely on their experience. Here, we present a novel machine learning based approach, which might make it possible to predict the size of the prosthesis from pre-operatively acquired ultrasound images. We utilize support vector regression to train a prediction model on three geometric features extracted from the ultrasound data. In order to evaluate the accuracy and robustness of our approach we created a large data base of porcine aortic root geometries in a healthy state and an artificially dilated state. Our results indicate that prediction of correct prosthesis sizes is feasible. Furthermore, they suggest that it is crucial that the training data set faithfully represents the diversity of aortic root geometries.

[Evaluation of Psychiatric Disorders on the Basis of a SCID Screening]. / Evaluation psychiatrischer Störungen anhand eines erweiterten SKID-Screenings.

BACKGROUND: Psychiatric symptoms/syndromes such as depression, apathy, anxiety or psychotic episodes are present in a range of neurological disorders including Parkinson's disease. The Structured Clinical Interview for DSM-IV (SCID) represents the gold standard for the assessment of psychiatric disorders but is often too time-consuming for application in clinical practice. METHODS: 66 participants were examined using the screening items and the first two questions of section A of the SCID as well as the complete version of the SCID, part I. The accuracy of the screening and the complete SCID was evaluated, and logistic regression was conducted to analyze factors associated with measure disagreement between the two procedures. RESULTS: Overall, psychiatric disorders were identified by screening in 40/66 (60.6%), as against 31/66 (47.0%) using the complete SCID. Compared to the complete SCID, the sensitivity and specificity of the screening items were 88% and 59%, respectively. CONCLUSION: Based on its good sensitivity, the SCID screening may be used in clinical practice to yield an overview of psychiatric disorders that may require treatment. Due to its moderate specificity, however, the complete version of the SCID should be subsequently used in cases whenever the SCID screening is positive. In any case, the SCID screening must be regarded as inadequate for the detection of psychotic symptoms.

Transcranial sonography and functional imaging in glucocerebrosidase mutation Parkinson disease.

BACKGROUND: Heterozygous glucocerebrosidase (GBA) mutations are the leading genetic risk factor for Parkinson disease, yet imaging correlates, particularly transcranial sonography, have not been extensively described. METHODS: To determine whether GBA mutation heterozygotes with Parkinson disease demonstrate hyperechogenicity of the substantia nigra, transcranial sonography was performed in Ashkenazi Jewish Parkinson disease subjects, tested for the eight most common Gaucher disease mutations and the LRRK2 G2019S mutation, and in controls. [(18)F]-fluorodeoxyglucose or [(18)F]-fluorodopa positron emission tomography is also reported from a subset of Parkinson disease subjects with heterozygous GBA mutations. RESULTS: Parkinson disease subjects with heterozygous GBA mutations (n = 23) had a greater median maximal area of substantia nigral echogenicity compared to controls (n = 34, aSNmax = 0.30 vs. 0.18, p = 0.007). There was no difference in median maximal area of nigral echogenicity between Parkinson disease groups defined by GBA and LRRK2 genotype: GBA heterozygotes; GBA homozygotes/compound heterozygotes (n = 4, aSNmax = 0.27); subjects without LRRK2 or GBA mutations (n = 32, aSNmax = 0.27); LRRK2 heterozygotes/homozygotes without GBA mutations (n = 27, aSNmax = 0.28); and GBA heterozygotes/LRRK2 heterozygotes (n = 4, aSNmax = 0.32, overall p = 0.63). In secondary analyses among Parkinson disease subjects with GBA mutations, maximal area of nigral echogenicity did not differ based on GBA mutation severity or mutation number. [(18)F]-fluorodeoxyglucose (n = 3) and [(18)F]-fluorodopa (n = 2) positron emission tomography in Parkinson disease subjects with heterozygous GBA mutations was consistent with findings in idiopathic Parkinson disease. CONCLUSIONS: Both transcranial sonography and positron emission tomography are abnormal in GBA mutation associated Parkinson disease, similar to other Parkinson disease subjects.

Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites.

OBJECTIVE: To compare the phenotype of primary-appearing dystonia due to variant ataxia-telangiectasia (A-T) with that of other dystonia ascertained for genetics research. METHODS: Movement disorder specialists examined 20 Canadian Mennonite adult probands with primary-appearing dystonia, as well as relatives in 4 families with parent-child transmission of dystonia. We screened for the exon 43 c.6200 C>A (p. A2067D) ATM mutation and mutations in DYT1 and DYT6. Clinical features of the individuals with dystonia who were harboring ATM mutations were compared with those of individuals without mutations. RESULT: Genetic analysis revealed a homozygous founder mutation in ATM in 13 members from 3 of the families, and no one harbored DYT6 or DYT1 mutations. Dystonia in ATM families mimicked other forms of early-onset primary torsion dystonia, especially DYT6, with prominent cervical, cranial, and brachial involvement. Mean age at onset was markedly younger in the patients with variant A-T (n = 12) than in patients with other dystonia (n = 23), (12 years vs 40 years, p < 0.05). The patients with A-T were remarkable for the absence of notable cerebellar atrophy on MRI, lack of frank ataxia on examination, and absence of ocular telangiectasias at original presentation, as well as the presence of prominent myoclonus-dystonia in 2 patients. Many also developed malignancies. CONCLUSION: Ataxia and telangiectasias may not be prominent features of patients with variant A-T treated for dystonia in adulthood, and variant A-T may mimic primary torsion dystonia and myoclonus-dystonia.

Autosomal dominant Parkinson's disease in a large German pedigree.

OBJECTIVE: While several genes have been identified to cause Parkinson's disease (PD), monogenic forms explain only a small proportion of cases. We report clinical and genetic results in a large family with late-onset autosomal dominant PD. METHODS: Thirty-eight family members of a five-generation Northern German PD family underwent a detailed neurologic examination, and transcranial sonography was performed in fifteen of them. Comprehensive mutation analysis of known PD-causing genes and a genome-wide linkage analysis were performed. RESULTS: Late-onset definite PD was found in five subjects with a mean age at onset of 63 years. Another six individuals presented either with probable/possible PD or with subtle parkinsonian signs. Six members with a mean age of 79 years had an essential tremor phenotype. Mode of PD inheritance was compatible with autosomal dominant transmission. One of three examined patients with definite PD demonstrated an increased area of substantia nigra hyperechogenicity upon transcranial sonography. Comprehensive linkage and mutational analysis excluded mutations in known PD-causing genes. Genome-wide linkage analysis suggested a putative disease gene in an 11.3-Mb region on chromosome 7p15-21.1 with a multipoint LOD score of 2.0. CONCLUSIONS: The findings in this family further demonstrate genetic heterogeneity in familial autosomal dominant late-onset PD.

[The presymptomatic stage of neurodegenerative disorders]. / Das präsymptomatische Stadium neurodegenerativer Erkrankungen.

Neurodegenerative disorders, such as Huntington's disease, spinocerebellar ataxias, Parkinson's disease or Alzheimer's disease, manifest in adult age with insidiously developing, slowly progressing symptoms. At this stage, most patients consult a doctor, and a definite diagnosis can be made. It is, however, well established that the manifest disease is preceded by a presymptomatic disease stage that may last for years. A striking example is Parkinson's disease, in which more than half of the dopaminergic neurons of the substantia nigra are lost before motor symptoms appear. Studies of the presymptomatic stage of neurodegenerative disorders are pivotal for an advanced understanding of these disorders and the development of preventive strategies aimed at postponing the clinical onset of these disorders. It is therefore important to identify the earliest and most sensitive clinical signs and biological markers that herald the onset of the illness. Furthermore, studies of presymptomatic disease stages are important because they may help to unravel compensatory mechanisms responsible for apparently normal brain function despite ongoing neurodegeneration.

[Sonography of the parenchyma in Parkinson's disease]. / Parenchym-Ultraschall bei Parkinson-Syndromen.

Transcranial sonography (TCS) of the brain parenchyma is a non-invasive and easily applicable neuroimaging technique which is used as a diagnostic tool in Parkinson's disease. Up to 90% of patients with idiopathic Parkinson's disease but only 10-15% of the healthy population show an abnormal echogenicity (hyperechogenicity) of the substantia nigra (SN). TCS has been demonstrated to be a useful tool in the differential diagnosis of patients with essential tremor or atypical parkinsonian syndromes, including the parkinsonian variant of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP) where hyperechogenicity of the SN is less frequent. Abnormal echogenicity of the SN has been found in almost all investigated monogenic types of parkinsonism and even in asymptomatic mutation carriers. The nature of the pathological substrate leading to the abnormal echogenicity of the SN remains elusive. Longitudinal studies of asymptomatic subjects with abnormal echogenicity of the SN are still ongoing to evaluate the risk for developing Parkinson's disease in the future in these subjects.

Progression of subtle motor signs in PINK1 mutation carriers with mild dopaminergic deficit.

BACKGROUND: While homozygous mutations in the PINK1 gene cause recessively inherited early-onset Parkinson disease (PD), heterozygous mutations have been suggested as a susceptibility factor. METHODS: To evaluate this hypothesis, 4 homozygous PINK1 patients with PD and 10 asymptomatic carriers of a single heterozygous mutation from a large German family (family W) were included in this study. Clinical follow-up of the heterozygous mutation carriers 3 years after the initial visit included a detailed videotaped neurologic examination using the Unified Parkinson's Disease Rating Scale III protocol and smell and color discrimination testing. At follow-up, PET with 18-fluorodopa (FDOPA) of 13 family members was obtained in order to evaluate the clinical phenotype in light of nigostriatal dopaminergic functioning. The clinical and PET data were compared to those of healthy controls. RESULTS: While there was mild worsening of clinical signs in previously affected heterozygous mutation carriers upon follow-up, 3 additional individuals had newly developed signs of possible PD. Hyposmia was found in 7 of the heterozygous mutation carriers, diminished color discrimination in 4. The homozygous mutation carriers who were all definitely affected with PD showed a severe, 60% decrease of caudate and putaminal FDOPA uptake; heterozygous offspring also had a significant 20% putaminal FDOPA uptake reduction compared to controls. CONCLUSIONS: Our findings strengthen the hypothesis that heterozygous PINK1 mutations act as a susceptibility factor to develop at least subtle Parkinson disease motor and nonmotor signs, as supported by the finding of a reduced striatal dopaminergic FDOPA uptake not only in homozygous but also, albeit to a lesser extent, in heterozygous mutation carriers.

[Transcraniel ultrasound in the differential diagnosis of Parkinson's disease]. / Stellenwert der Hirnparenchym-Sonografie in der Differenzial- und Frühdiagnose des Parkinson-Syndroms.

Imaging of the brain structure with transcranial ultrasound has become an important tool for the diagnosis and differential diagnosis of Parkinson's Disease. In up to 90 % of parkinsonian patients abnormal echogenity of the substantia nigra could be demonstrated. Particularly in the early diagnosis in subjects with only very mild extrapyramidal features and in the differential diagnosis to other neurodegenerative disorders with parkinsonian features, such as the parkinsonian variant of multisystematrophy (MSA-P) and progressive supranuclear paralysis (PSP) ultrasound has a high diagnostic yield. Because of a prevalence of about 10 % in the normal population, the evidence of an abnormal echogenity of the substantia nigra has to be interpreted carefully in the context of a clinical examination. Although there are a number of studies indicating that in some of these subjects a vulnerability of the nigrostriatal system can be found, the meaning of an abnormal echogenicity of the substantia nigra in the healthy population needs to be further elucidated in already ongoing research projects.

[Central sleep apnea in multiple sclerosis]. / Zentrales Schlafapnoe-Syndrom bei multipler Sklerose.

Fatigue is a common problem in patients suffering from multiple sclerosis (MS). The presented case demonstrated concomitant severe central sleep apnea. Selection of the optimal ventilation modus was complex but proved successful. Given that daytime sleepiness is a frequent symptom in MS patients and that effective treatment options are available, sleep apnea should be considered and further classified by polysomnography in order to improve patients' quality of life.

Primary focal dystonia: evidence for distinct neuropsychiatric and personality profiles.

BACKGROUND: Primary focal dystonia (PFD) is characterised by motor symptoms. Frequent co-occurrence of abnormal mental conditions has been mentioned for decades but is less well defined. In this study, prevalence rates of psychiatric disorders, personality disorders and traits in a large cohort of patients with PFD were evaluated. METHODS: Prevalence rates of clinical psychiatric diagnoses in 86 PFD patients were compared with a population based sample (n = 3943) using a multiple regression approach. Furthermore, participants were evaluated for personality traits with the 5 Factor Personality Inventory. RESULTS: Lifetime prevalence for any psychiatric or personality disorder was 70.9%. More specifically, axis I disorders occurred at a 4.5-fold increased chance. Highest odds ratios were found for social phobia (OR 21.6), agoraphobia (OR 16.7) and panic disorder (OR 11.5). Furthermore, an increased prevalence rate of 32.6% for anxious personality disorders comprising obsessive-compulsive (22.1%) and avoidant personality disorders (16.3%) were found. Except for social phobia, psychiatric disorders manifested prior to the occurrence of dystonia symptoms. In the self-rating of personality traits, PFD patients demonstrated pronounced agreeableness, conscientiousness and reduced openness. CONCLUSIONS: Patients with PFD show distinct neuropsychiatric and personality profiles of the anxiety spectrum. PFD should therefore be viewed as a neuropsychiatric disorder rather than a pure movement disorder.

Etiology of musician's dystonia: familial or environmental?

OBJECTIVE: To test the hypothesis that there is familial aggregation of dystonia and other movement disorders in relatives of patients with musician's dystonia (MD) and to identify possible environmental triggers. METHODS: The families of 28 index patients with MD (14 with a reported positive family history of focal task-specific dystonia [FTSD] and 14 with no known family history [FH-]) underwent a standardized telephone screening interview using a modified version of the Beth Israel Dystonia Screen. Videotaped neurologic examinations were performed on all participants who screened positive and consensus diagnoses established. All patients were investigated for DYT1 dystonia and suitable families were tested for linkage to DYT7. All family members were administered questionnaires covering potential triggers of FTSD. RESULTS: A diagnosis of dystonia was established in all 28 index patients and in 19/97 examined relatives (MD: n = 8, other FTSD: n = 9, other dystonias: n = 2), 5 of whom were members of FH- families. In 27 of the 47 affected individuals, additional forms of dystonia were seen; other movement disorders were observed in 23 patients. In total, 18 families were multiplex families with two to four affected members. Autosomal dominant inheritance was compatible in at least 12 families. The GAG deletion in DYT1 was absent in all patients. Linkage to DYT7 could be excluded in 1 of the 11 informative families. With respect to potential environmental triggers, there was no significant difference between patients with MD/FTSD compared to unaffected family members. CONCLUSION: Our results suggest a genetic contribution to musician's dystonia with phenotypic variability including focal task-specific dystonia.

Somatosensory processing in a German family with PINK1 mutations: its potential role in Parkinson disease.

BACKGROUND: It is unclear whether sensory symptoms in Parkinson disease (PD) are of primary or of secondary origin attributable to motor symptoms such as rigidity and bradykinesia. OBJECTIVE: The aim of this study was to elucidate whether sensory abnormalities are present and may precede motor symptoms in familial parkinsonism by characterizing sensory function in symptomatic and asymptomatic PINK1 mutation carriers. METHODS: Fourteen family members with PINK1 mutation and 14 healthy controls were examined clinically, with nerve conduction studies and quantitative sensory testing (QST). RESULTS: Thresholds for mechanical detection, mechanical pain and pressure pain were higher in PINK1 mutation carriers compared to controls. Higher thresholds for mechanical detection, mechanical pain and pressure pain were even found in asymptomatic, clinically not or only mildly affected PINK1 mutation carriers. CONCLUSIONS: Data suggest that PINK1-associated PD is associated with a primary hypofunction of nociceptive and non-nociceptive afferent systems that can already be found at the time when motor signs of PD are only subtle. As nerve conduction studies did not reveal differences between PINK1 mutation carriers and controls, we propose that the somatosensory impairment is related to abnormal central somatosensory processing.

Heterozygous carriers of a Parkin or PINK1 mutation share a common functional endophenotype.

OBJECTIVE: To use a combined neurogenetic-neuroimaging approach to examine the functional consequences of preclinical dopaminergic nigrostriatal dysfunction in the human motor system. Specifically, we examined how a single heterozygous mutation in different genes associated with recessively inherited Parkinson disease alters the cortical control of sequential finger movements. METHODS: Nonmanifesting individuals carrying a single heterozygous Parkin (n = 13) or PINK1 (n = 9) mutation and 23 healthy controls without these mutations were studied with functional MRI (fMRI). During fMRI, participants performed simple sequences of three thumb-to-finger opposition movements with their right dominant hand. Since heterozygous Parkin and PINK1 mutations cause a latent dopaminergic nigrostriatal dysfunction, we predicted a compensatory recruitment of those rostral premotor areas that are normally implicated in the control of complex motor sequences. We expected this overactivity to be independent of the underlying genotype. RESULTS: Task performance was comparable for all groups. The performance of a simple motor sequence task consistently activated the rostral supplementary motor area and right rostral dorsal premotor cortex in mutation carriers but not in controls. Task-related activation of these premotor areas was similar in carriers of a Parkin or PINK1 mutation. CONCLUSION: Mutations in different genes linked to recessively inherited Parkinson disease are associated with an additional recruitment of rostral supplementary motor area and rostral dorsal premotor cortex during a simple motor sequence task. These premotor areas were recruited independently of the underlying genotype. The observed activation most likely reflects a "generic" compensatory mechanism to maintain motor function in the context of a mild dopaminergic deficit.