[Big data and deep learning in preventive and rehabilitation medicine]. / Big Data und maschinelles Lernen bei Prävention und Rehabilitation.

The digitalization in medicine has led to almost universal availability of information to different healthcare professionals and accelerated clinical pathways. Fast-track concepts and short hospital stays require intelligent and practicable systems in preventive and rehabilitation medicine. This includes optimization of movement analysis by innovative tools such as detectors sensing skin movements, portable feedback systems for monitoring, robot-assisted devices, and prevention programs based on reliable data. Finally, clinical structures are needed to exploit the maximal potential of artificial intelligence (AI) and deep learning. One example is the establishment of inter- and transdisciplinary professional teams such as a RehaBoard. In contrast to other cost-intensive disciplines such as oncology, the introduction of AI into rehabilitation orthopedics and trauma surgery with the support of cross-sectoral cooperation has great potential for performing well in patient benefit-orientated competition (value-based competition).

Gait deviations in transverse plane after SCFE in dependence on the femoral offset.

Residual deformity of the femoral head after slipped capital femoral epiphysis (SCFE) may be accompanied by a loss of femoral offset and lead to femoro-acetabular impingement (FAI), especially during hip flexion. It is hypothesized that during phases of the gait cycle, when the hip is flexed, the offset-loss is compensated by an increased external rotation. The gait pattern of 36 patients suffering from SCFE, who were treated by pinning-in-situ, were compared to a control group of 40 healthy adults by an instrumented 3D-gait analysis. Total patient group was subdivided into 3 subgroups in dependence on the offset (offset groups (OG)) quantified by the angle α according to Nötzli: OG1: α-angle <55°, OG2: α-angle between 55 and 75°, OG3: α-angle >75°. Comparisons were made at 3 instants: initial foot contact (0% gait cycle (GC)), 40-60% GC and 90-100% GC. Patients showed an increased external hip rotation during all 3 periods of the GC with a tendency of increasing external rotation in association with offset-loss. Only during hip extension (40-60% GC) there was a weak correlation between angle α and hip rotation (r=-0.375, p=0.024). In conclusion, the offset-loss does not lead to a functional relevant impingement during walking which needs compensation strategies like increasing external rotation during periods of hip flexion.

An open-label cohort study of the improvement of quality of life and pain in de novo cervical dystonia patients after injections with 500 U botulinum toxin A (Dysport).

OBJECTIVES: It remains to be determined whether the benefits of botulinum toxin type A (BoNT-A) on cervical dystonia (CD) motor symptoms extend to improvements in patient's quality of life (QoL). This analysis of a large, multicentre study was conducted with the aim of investigating changes in QoL and functioning among de novo patients receiving 500 U BoNT-A (abobotulinumtoxinA; Dysport) for the treatment of the two most frequent forms of CD, predominantly torticollis and laterocollis. DESIGN: A prospective, open-label study of Dysport (500 U; Ipsen Biopharm Ltd) administered according to a defined intramuscular injection algorithm. SETTING: German and Austrian outpatient clinics. PARTICIPANTS: 516 male and female patients (aged ≥18 years) with de novo CD. The majority of patients had torticollis (78.1%). 35 patients had concomitant depression (MedDRA-defined). MAIN OUTCOME MEASURES: Change from baseline to weeks 4 and 12 in Craniocervical Dystonia Questionnaire (CDQ-24) total and subscale scores, patient diary items ('day-to-day capacities and activities', 'pain' and 'duration of pain') and global assessment of pain. RESULTS: Significant improvements were observed in CDQ-24 total and subscale scores at week 4 and were sustained up to week 12 (p<0.001). Changes in CDQ-24 scores did not significantly differ between the torticollis and laterocollis groups or between patients with or without depression. There were also significant reductions in patient diary item scores for activities of daily living, pain and pain duration at weeks 4 and 12 (p<0.001). Pain relief (less or no pain) was reported by 66% and 74.1% of patients at weeks 4 and 12, respectively. Changes in pain parameters demonstrated a positive relationship with change in Tsui score. CONCLUSIONS: After standardised open-label treatment with Dysport 500 U, improvements in QoL and pain intensity up to 12 weeks in patients with CD were observed.

A case of relapsing-remitting neuroborreliosis? Challenges in the differential diagnosis of recurrent myelitis.

We report the case of a 31-year-old woman with 4 episodes of myelitis with pleocytosis, a positive Borrelia burgdorferi serology with positive antibody indices, and full recovery each time after antibiotic and steroid treatment, suggesting neuroborreliosis. We nevertheless believe that recurrent neuroborreliosis is improbable based on the levels of the chemokine CXCL13 in cerebrospinal fluid and favor the diagnosis of post-infectious autoimmune-mediated transverse myelitis possibly triggered by an initial neuroborreliosis as the cause of the relapses observed in our patient. We demonstrate the diagnostic steps and procedures which were important in the differential diagnosis of this unusual and challenging case.

[Superficial siderosis of the central nervous system in a patient with hemochromatosis and Wilson's disease]. / Superfizielle Siderose des zentralen Nervensystems bei einem Patienten mit Hämochromatose und Morbus Wilson.

HISTORY AND FINDINGS ON ADMISSION: A 55-year-old patient with a history of Wilson's disease and biopsy proven hemochromatosis complained of hearing loss, vertigo, and gait disturbance. Clinical examination confirmed hearing loss, revealed cerebellar syndrome and bilateral pyramidal tract disturbances. INVESTIGATIONS: Neurophysiology confirmed pathological findings on clinical examination. Cerebral magnetic resonance imaging (MRI) disclosed deposition of hemosiderin suggestive for superficial siderosis of the central nervous system. Cerebrospinal fluid findings were normal. DIAGNOSIS: The triad of hearing loss, cerebellar syndrome, and pyramidal tract disturbances associated with typical findings on MRI led to diagnosis of superficial siderosis. CLINICAL COURSE AND THERAPY: Etiology in this case remained unclear; no source of bleeding was detected. Thus, no causal therapeutic option was available. CONCLUSION: A unique case of superficial siderosis in a patient with a history of Wilson's disease and hemochromatosis is presented. Unexpected new symptoms in a successfully treated Wilson's disease patient require further diagnostic work-up not to miss potentially curable differential diagnoses. Thus, regular neurological follow-up visits of Wilson's disease patients are required.

Phase relations between rhythmical movements and breathing in wind instrument players.

In 18 healthy age- and sex- matched controls and 13 patients with Wilsons disease (18-50 years) under continuous copper chelating therapy sinusoidal forearm movements of a given target rates (target rates: 0.2, 0.3, 0.4, 0.5, 0.6 Hz) as well as breathing movements were recorded by means of a goniometer and a breathing girdle in parallel. Additionally, controls and patients had to perform spontaneous forearm movements at their most comfortable rate. The percentage of time during which forearm and breathing movements were coupled was significantly reduced in the patients. With increasing target rate the mean breathing rate significantly increased in the controls but not in the patients. Furthermore, the variability of breathing rate significantly increased in the patients but not in the controls. These two factors probably caused that the coupling of breathing and extremity movements was significantly reduced in the patients.

[Aspects of the complexity of cervical dystonia]. / Aspekte der möglichen Komplexität zervikaler Dystonien.

Most cases of cervical dystonia (CD) can easily be treated by injections of botulinum toxin A (BTX-A) into a few cervical muscles among which the splenius capitis, the semispinalis capitis the levator scapulae and the scalenii muscles are the most important ones whereras the trapezius and the sternocleidomastoideus muscles are of less importance. However, in some cases of CD the treatment of these easily injectable muscles does not lead to a satisfactory clinical outcome. Damage of and compensatory increase of connective tissue in muscles, additional activation of non-injected muscles by special motor tasks as lying, sitting, standing, walking and speaking and involvement of deep muscles remaining usually untreated may add to the complexity of treatment of cervical dystonia.

Validity of S-100 B in patients after brain radiation.

BACKGROUND: S-100B is a calcium binding acute phase protein and a potential biomarker for brain injury. In prior studies elevated plasma S-100B levels were detected in stroke and severe head trauma. The aim of this study was to evaluate whether S-100 B is elevated during cerebral radiotherapy and whether that is associated with adverse outcomes. MATERIAL AND METHODS: In this prospective pilot study, 45 patients (25 males, 20 females, median age 58 (17-81)) underwent cerebral radiation therapy because of a primary or metastaic cerebral malignancy. 39 patients were included in the evaluation. 6 patients died during the study period. S-100 plasma concentrations were measured with an electrochemiluminescence immunoassay on admission and weekly during radiation therapy for the duration of 6 weeks. In 10 healthy young volunteers (5 males, 5 females, median age 32 (28-36)) S-100 B plasma levels were measured weekly for 6 weeks as a negative control. Furthermore, in an active control 10 patients (4 males, 6 females, median age 68 (64-76)) with stroke (7 = major stroke, 3 = lacunar infarct) S- 100 B plasma levels were measured for 7 consecutive days after the event. RESULTS: During radiotherapy S-100 B plasma concentrations increased from median baseline values of 0.030 microg/l to 0.044 microg/l. For the time of radiation therapy most patients showed a mild increase, but absolute plasma values were still within the normal range. In the control group of healthy volunteers S-100 B remained unchanged. In stroke patients S-100 B increased to maximum values of 1.7 microg/l three days after the event. In the 3 patients with lacunar infarcts no increase of S-100 B levels could be detected. CONCLUSION: Brain irradiation leads to a mild increase of S-100 B plasma levels. However, the absolute rise was far weaker compared to that seen in major brain injuries.

[How reliable are data from 3d-gait analysis]. / Wie reliabel sind Informationen aus der 3D-Ganganalyse?

AIM: The aim of the present study was to collect preliminary data to determine the test-retest reliability in healthy subjects using 3-dimensional computerised gait analysis. METHOD: Ten healthy subjects (6 females, 4 males) were tested using a 3-dimensional computerized gait analysis system (VICON 512, Oxford Metrics). There were two trials within a 2-hour period in which kinetic, kinematic and time-distance data were collected. Markers were removed after the first trial and reapplied for the second trial and Pearson's correlation coefficients were calculated. RESULTS: The correlation coefficients were all positive and high for time-distance (r = 0.86-0.99), sagittal plane kinematics (r = 0.86-0.98) and power (r = 0.90-0.98) parameters, indicating excellent reliability of these measures. Correlation coefficients for frontal and transverse plane kinematics were lower (r = 0.59-0.89). The lowest correlation coefficient values were obtained for transverse plane measures at the hip joint indicating poor reliability of this measure in healthy subjects. CONCLUSION: The results suggest excellent test-retest reliability using 3-dimensional computerized gait analysis, especially in the sagittal plane. Therefore this method is a very valuable tool in the analysis as well as in the outcome evaluation of conservative and operative procedures in movement disorders

Potential c-fiber damage in Wilson's disease.

OBJECTIVES: To find out about potential involvement of the peripheral and autonomic nervous system in Wilson's disease (WD). MATERIAL AND METHODS: Seventeen patients with laboratory proven WD were examined with quantitative sensory testing (QST) (thermal, pain and vibratory sensation), pupillometric evaluation and electrophysiological testing of basal ganglia motor function [frequency of most rapid alternating movements (MRAM), reaction time (RT), contraction time (CT)]. Results were compared with those obtained in 20 healthy controls. RESULTS: After correction for multiple comparisons, patients with WD showed significantly higher thresholds for warm sensation [sural and peroneal nerve, thermal sensory limen (TSL), unpaired t-test]. Individual results were pathological in eight (peroneal) and nine (sural nerve) patients, respectively. Pupil function was not altered. Patients with WD showed significant slowing of MRAM and prolongation of RT and CT. There was no significant correlation between RT and QST results. CONCLUSIONS: These findings are compatible with a potential involvement of unmyelinated warm-specific C fibers in WD, independent from predominant basal ganglia motor dysfunction.

The phenylalanine loading test in the differential diagnosis of dystonia.

Early diagnosis of dopa-responsive dystonia (DRD) and its delineation from other dystonic syndromes is of great relevance because DRD is an eminently treatable condition. The possible relevance of the phenylalanine loading test (Phe-L) in differentiating DRD from primary focal and generalized dystonia was investigated. A marked difference in the phenylalanine/tyrosine ratio between patients with DRD and patients with other types of dystonia was observed. This indicates that Phe-L may be helpful in the differential diagnosis of dystonias.

[Early pain reduction in the treatment of spasticity after a single injection of botulinum A toxin]. / Frühe Schmerzreduktion in der Therapie von Spastik nach einmaliger Botulinustoxin-A-Injektion.

UNLABELLED: HISTORY, ADMISSION FINDINGS AND DIAGNOSIS: After stem-cell transplantation a 45-year-old woman (case 1) had an attack of general hypoxia requiring resuscitation. She then developed a quadriplegia and spasticity of all limbs notably of the right arm and a severe pain syndrome which had to be treated by oral and intravenous analgesics. Immobilisation and secondary complications aggravated the already difficult situation. In the 2nd case a 66-year-old woman was admitted to our outpatient clinic with long-standing left-sided spastic hemiparesis after territorial infarction of the right middle cerebral artery. Beside the spasticity she also suffered from a distinct pain syndrome which did not respond to any oral analgesics. TREATMENT AND COURSE: For the treatment of the main symptoms, both patients received intramuscular injections of 1000 MU botulinum toxin A (Dysport(R) Ipsen Pharma). Astonishingly, both patients experienced pain relief the next day, whereas spasticity started to respond only 5-6 days later. CONCLUSIONS: In our experience pain relief after botulinum toxin A injections occurs not only due to reduced muscle hyperactivity, especially when such a temporal dissociation between pain relief and muscle relaxation appears as in the two cases reported above. Rather, we believe that botulinum toxin A interferes with the release of other neurotransmitters e. g. substance P (SP) and calcitonine-gene-related-peptide (CGRP) having a key function in the nociceptive cascade.

Effects of bilateral pallidal or subthalamic stimulation on gait in advanced Parkinson's disease.

Bilateral high-frequency stimulation of the internal globus pallidus (GPi) and the subthalamic nucleus (STN) both alleviate akinesia, rigidity, and tremor in idiopathic Parkinson's disease. To test the specific effect of these procedures on gait, we used quantitative gait analysis in addition to relevant subscores of the Unified Parkinson's Disease Rating Scale in a group of 10 patients with advanced Parkinson's disease treated by GPi stimulation and eight patients treated by STN stimulation. Patients were assessed before and 3 months after surgery. Thirty age-matched healthy subjects served as controls. The non-random selection allowed a descriptive but no direct statistical comparison of the respective procedure. Gait analysis showed significant stimulation-induced improvements of spatiotemporal gait and step parameters in both patient groups. Moreover, the effects on step length and cadence suggested a differential effect of both basal ganglia targets. Hence, the increase in gait velocity in the STN group was almost exclusively due to a significant increase in step length, while in the GPi group statistically non-significant increases in both step length and cadence contributed.

[Rediscovery of thalidomide. Successful treatment of discoid lupus erythematosus]. / Wiederentdeckung von Thalidomid. Erfolgreiche Behandlung des chronisch diskoiden Lupus erythematodes.

Thalidomide, an oral drug introduced in Germany in 1953 as a mild sedative, was withdrawn from the world market when its teratogenic effect was discovered some years later. It has since been selectively reintroduced to treat a variety of autoimmune or inflammatory diseases such as erythema nodosum leprosum, prurigo nodularis, graft-versus-host disease, and discoid lupus erythematosus (DLE). We report on three patients with long-standing, severe DLE showing no response to systemic first-, second- and third-line treatments. After four weeks of therapy with thalidomide the skin lesions had improved dramatically and after three to six months all three patients responded with an almost complete remission. The side effects of thalidomide, especially somnolence and paresthesias, were minor and well tolerated by the patients. Our data confirm that thalidomide provides one of the most useful therapeutic alternatives for chronic refractory DLE, despite the risks of teratogenicity and polyneuropathy.

Basal ganglia metabolite abnormalities in minor motor disorders associated with human immunodeficiency virus type 1.

BACKGROUND: Minor motor disorders (MMDs) associated with human immunodeficiency virus type 1 (HIV-1) predict HIV-1 dementia and death. Little is known about the time course and neuropathologic mechanisms of HIV-1 MMDs. OBJECTIVE: To investigate the relationship between HIV-1 MMDs, as assessed by psychomotor speed, and metabolic alterations in the basal ganglia, as detected by proton magnetic resonance spectroscopy. PATIENTS AND METHODS: A total of 32 HIV-1-seropositive patients (10 with no MMD, 8 with incipient MMD, and 14 with sustained MMD, assessed through electrophysiologic testing of psychomotor speed including contraction times; 29 treated with highly active antiretroviral therapy) and 14 HIV-1-seronegative control subjects were examined for cerebral metabolite abnormalities in the basal ganglia by means of magnetic resonance spectroscopy. RESULTS: The 3 patient groups showed significantly different ratios of myoinositol/creatine (P =.02) in the basal ganglia. Whereas patients with no MMD or incipient MMD showed normal ratios, patients with sustained MMD showed higher values for myoinositol/creatine as a sign of glial proliferation. No differences in N-acetyl compounds, indicative of neuronal loss, were found. CONCLUSION: Whereas metabolic alterations in the basal ganglia were not detected in patients with incipient HIV-1 MMD, patients with sustained HIV-1 MMD did have significantly altered metabolic spectra indicative of glial proliferation.

Neural correlates of religious experience.

The commonsense view of religious experience is that it is a preconceptual, immediate affective event. Work in philosophy and psychology, however, suggest that religious experience is an attributional cognitive phenomenon. Here the neural correlates of a religious experience are investigated using functional neuroimaging. During religious recitation, self-identified religious subjects activated a frontal-parietal circuit, composed of the dorsolateral prefrontal, dorsomedial frontal and medial parietal cortex. Prior studies indicate that these areas play a profound role in sustaining reflexive evaluation of thought. Thus, religious experience may be a cognitive process which, nonetheless, feels immediate.

[Reduction of pain and muscle spasms by botulinum toxin A]. / Reduktion von Schmerzen und Muskelanspannung durch Botulinum-Toxin A.

Botulinum toxin A (BoNT-A) develops its muscle-relaxing effect by the inhibition of acetylcholine (ACh) release. This toxin is also known to relieve muscular pain in different disorders. Conspicuously, pain in some patients responds earlier and sometimes even better than muscle tension, indicating that the effect of BoNT-A on pain is not only due to inhibition of ACh release. A questionnaire was distributed to 88 patients suffering from cervical dystonia (CD). Thirty-five completed questionnaires could be used for data analysis. After intramuscular injections of BoNT-A, patients with CD experience significant reductions in pain which sometimes occur significantly earlier than the improvements in head posture. In the iris sphincter muscle of the rabbit and in dorsal root ganglion cells (DRG) of the rat, inhibition of the release of substance P by BoNT-A has been shown experimentally, and BoNT-C has been proven to develop endopeptidase activity toward substance P (SP) in vitro. Findings in the current literature and our observations allow the conclusion that alleviation of muscle pain by BoNT-A may also be due to an effect on the release of nociceptive neuropeptides, among which SP seems to have a key function.

Therapeutic effects of nucleoside analogues on psychomotor slowing in HIV infection.

OBJECTIVE: Since psychomotor slowing predicts the development of HIV-1-associated dementia, AIDS and death independently of the immune status, there is urgent need for a neurological therapeutic rationale. METHODS: The therapeutic efficacy of nucleoside analogues with different abilities to penetrate into the cerebrospinal fluid was assessed in 410 HIV-1-seropositive patients using the results of detailed fine motor tests, which detect minor motor deficits. Patients were selected who showed pathological psychomotor slowing as signs of central nervous system (CNS) dysfunction before therapy onset and who were then treated only with nucleoside analogues for at least 6 months. RESULTS: Both zidovudine and didanosine improve CNS function to an equal degree when given as monotherapy. Adding a second nucleoside analogue (didanosine, lamivudine, zalcitabine) to zidovudine does not further improve psychomotor performance. However, adding a second nucleoside after a period of zidovudine monotherapy does result in a second but less remarkable therapeutic effect. Combinations containing stavudine are as effective as those including zidovudine when given as first antiretroviral treatment. Furthermore, stavudine effectively improves motor performance even after pretreatment with zidovudine.