[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).

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.

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.

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.

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.

His1069Gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype.

In the present study we examined 33 German and 10 Cuban unrelated Wilson disease (WND) index patients and their relatives. The common His1069Gln mutation accounted for 42% of all WND chromosomes in the German series and the haplotype C was found to be highly predictive for this mutation. Six WND gene mutations have not been described previously and involved a splice site at intron 18 (3903 + del1G), a termination codon in the copper-binding region of exon 2 (Cys271X), and missense mutations in transmembrane region 2 (Gly710Ala), in transmembrane region 3 (Tyr741Cys), in the DKTGT motif (Thr1031Ile) and in the ATP loop region (Gly1176Arg). In 15 German WND index patients and three sibs both WND mutations could be determined and a genotype-phenotype correlation was attempted. Patients homozygous for the His1069Gln mutation showed almost the complete range of clinical presentations, and thus in our study this mutation is not associated with a late, neurological presentation.

Potential time course of human immunodeficiency virus type 1-associated minor motor deficits: electrophysiologic and positron emission tomography findings.

BACKGROUND: We tested whether metabolic abnormalities in the prefrontal-striatal circuitry as demonstrated by positron emission tomography (PET) were present in patients seropositive for human immunodeficiency virus type 1 (HIV-1) with HIV-1-associated minor motor deficits as demonstrated by quantitative motor testing. PATIENTS: We examined 19 HIV-1-positive patients, covering the range from normal results of quantitative motor testing to clearly pathologic psychomotor slowing indicative of HIV-1-associated minor motor deficits. None fulfilled the clinical criteria for HIV-1-associated dementia. Results were compared with those of 15 healthy volunteers. METHODS: All subjects underwent clinical examination, routine magnetic resonance (MR) imaging, and electrophysiologic motor testing at the time of PET. RESULTS: Seven HIV-1-positive patients showed significant hypermetabolism in the basal ganglia. Nine patients showed a significant frontomesial hypometabolism. CONCLUSIONS: The data of our cross-sectional study strongly suggest a characteristic time course in the development of HIV-1-associated minor motor deficits. Hypermetabolism in the basal ganglia is associated initially with normal motor performance. Moderate motor slowing appears at a later stage when basal ganglia hypermetabolism drops toward hypometabolism. More severe functional deficits and highly pathologic motor slowing become manifest when hypometabolism is most widespread in the basal ganglia. This stage leads to dementia.

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.

Improvement of motor performance of HIV-positive patients under AZT therapy.

We performed motor tests (most rapid alternating movements [MRAMs] of index fingers and most rapid contractions [MRCs] of voluntary isometric index finger extensions) in HIV-positive patients with (group 1) and without (group 2) AZT treatment over a 6-month period. Whereas MRAMs remained uninfluenced, MRCs showed a clear improvement in the treated group and a decline in the nontreated group, according to the T helper cell counts. MRCs were not only a sensitive test procedure for detecting subclinical lesions in HIV-positive patients, but also a reliable therapy control measurement.

Cerebral manifestation of Wilson's disease successfully treated with liver transplantation.

The main indication for orthotopic liver transplantation (OLTx) in Wilson's disease (WD) is severe hepatic decompensation. Our 15-year-old patient is the second case to date in whom OLTx was performed because of neurologic manifestations resulting from WD. His initial condition involving recurrent headaches, tremor, and athetoid hand movements progressively deteriorated during therapy with D-penicillamine, zinc sulfate, and trientine until he was severely dysarthric, unable to walk, and bedridden. After OLTx, his neurologic condition became almost normal.

Human anterior intraparietal area subserves prehension: a combined lesion and functional MRI activation study.

It has been shown in nonhuman primates that the posterior parietal cortex is involved in coordination of arm and eye movements in space, whereas the anterior intraparietal area in the anterior lateral bank of the intraparietal sulcus plays a crucial role in fine finger movements, such as grasping. In this study we show by optoelectronic movement recordings that patients with cortical lesions involving the anterior lateral bank of the intraparietal sulcus have selective deficits in the coordination of finger movements required for object grasping, whereas reaching is much less disturbed. Patients with parietal lesions sparing the cortex lining the anterior intraparietal sulcus showed intact grasping behavior. Complementary evidence was obtained from functional MRI in normal control subjects showing a specific activation of the anterior lateral bank of the intraparietal sulcus during grasping. In conclusion, this combined lesion and activation study suggests that the anterior lateral bank of the intraparietal sulcus, possibly including the human homologue of the anterior intraparietal area, mediates the processing of sensorimotor integration of precisely tuned finger movements in humans.

Motor impairment in patients with parietal lesions: disturbances of meaningless arm movement sequences.

The execution of meaningless movement sequences was studied in 12 patients with lesions of the parietal cortex in comparison to the performance of age- and sex-matched controls. Five sequences of increasing complexity had to be performed by imitation and after verbal instruction. The performance errors were qualitatively scored by means of four error categories (temporal or spatial error, addition or omission of movement components). This study examined whether the error scores depended on instruction modality, movement complexity or lesion side. Patients with left parietal lesions produced more errors than those with right parietal lesions and control subjects. While additions or omissions of movement components occurred almost equally in all groups, temporal and spatial errors were more frequent in patients with left parietal lesions only. In addition, only the latter group showed a significant increase of error rates with increasing movement complexity. There were no significant differences between the contra- and ipsilesional hand in any group. These results demonstrate that lesions in the left parietal lobe lead to a disturbed spatio-temporal organisation of movement that becomes increasingly prominent for more complex movements.

Different coupling for the reach and grasp components in bimanual prehension movements.

In this study on functional coupling in bimanual grasping movements, nine normal subjects had to reach and grasp two different objects simultaneously. Both objects could be either small or large, resulting in four different conditions of bimanual grasping. The main dependent variables were the coupling coefficients calculated either between the hand displacements or between the grip apertures of both hands, serving as variables for the coupling of the reach and the grasp component respectively. The correlation was significantly higher for the reach component than for the grasp component, with only the latter one changing significantly with variation of object size. These findings suggest different temporo-spatial coupling modes for the reach and the grasp components of bimanual grasping movements.

Stavudine and the peripheral nerve in HIV-1 infected patients.

Stavudine (2',3'-didehydro-3'deoxythymidine) is a pyrimidine analogue that may be of great value in combination antiretroviral therapy (ART) for treating patients infected with human immunodeficiency virus type 1 (HIV-1). We assessed potential neurotoxic side effects by comparing peripheral nerve function in patients receiving ART including stavudine (n = 107) with that of patients receiving ART with zidovudine (n = 103). A cross-sectional analysis of electroneurographic data revealed no significant differences. In a follow-up examination of 31 patients newly started on ART with stavudine we observed no significant effects of the drug on electrophysiological measures. At a daily dose of 1.0 mg/kg the incidence of peripheral nervous system disease in our patients was about 10%. Repeated follow-up analysis of 13 patients on stavudine showed a significant reduction in sural nerve amplitude. Quantitative sensory testing in 13 patients revealed no systematic effect of stavudine on small nerve fibers. Peripheral nerve function in HIV-1 seropositive patients on ART with stavudine did not differ significantly from that in patients on ART with zidovudine. Therefore stavudine at a daily dose of 1.0 mg/kg is an alternative for patients who do not tolerate, or who have become resistant to zidovudine and can be recommended as a first-line drug in combination ART.

Treatment of chronic relapsing inflammatory demyelinating polyneuropathy by cyclosporin A and plasma exchange. A case report.

A patient with chronic relapsing inflammatory demyelinating polyneuropathy was successfully treated with plasma exchanges and cyclosporin A (CsA). Dynamometric measurements of hand force during the time of CsA treatment showed a highly significant correlation between hand force and CsA blood levels. The largest influence of CsA on hand force occurred 11-13 days after CsA uptake.

Motor dysfunction in HIV-infected patients without clinically detectable central-nervous deficit.

Motor tests were performed in 50 HIV-infected patients in all stages according to the current CDC classification, but without any clinically evident central nervous system deficit, and the results compared with an age-matched control group. Patients were excluded from the study if there was alcohol or drug abuse, fever and/or opportunistic cerebral infection. The parameters tested were postural tremor of the outstretched hands, most rapid voluntary alternating index finger movements (MRAM) and rise time of most rapid index finger extensions (MRC). Whereas tremor peak frequencies did not differ significantly in the patients and controls, MRAM and rise times of MRCs showed significant slowing in the patient group. Morphologically, the motor test performance of the HIV-infected patients was similar to that of patients with manifest basal ganglia disease (Parkinson's, Huntington's and Wilson's diseases). MRI scans of all patients were normal. It is concluded that in HIV-infected patients there is a very early subclinical central nervous system affection, especially of the basal ganglia, which is detectable with appropriate, quantitative motor function tests. These functional abnormalities precede the structural alterations in the MRI scans.

Dopamine D2 receptor binding and cerebral glucose metabolism recover after D-penicillamine-therapy in Wilson's disease.

Regional cerebral glucose metabolism (rCMRGlc) and dopamine D2 receptor binding were measured in a 31-year-old, severely affected, untreated patient with Wilson's disease of 3 years' duration using positron emission tomography and 18F-deoxyglucose and 18F-methylspiperone ([18F]MSP), respectively. There was a severe reduction of striatal and extrastriatal rCMRGlc as well as of striatal [18F]MSP accumulation rate. After 1 year of treatment with D-penicillamine, striatal and extrastriatal rCMRGlc and striatal [18F]MSP accumulation rate reached almost normal levels. It is hypothesized that recovery of motor functions due to copper trapping therapy was associated with an increase in basal ganglia activity and a re-expression or upregulation of dopamine D2 receptors.

Focal brain lesions in patients with AIDS: aetiologies and corresponding radiological patterns in a prospective study.

We report the results of a hospital-based study of 188 consecutive patients seropositive for the human immune deficiency virus type 1 (HIV-1) who presented in a 4-year period (1988-1991) with possible signs or symptoms of first-ever central nervous system disease. Confirmed diagnoses were cerebral toxoplasmosis in 47 patients (25.0%), HIV-1 encephalopathy in 19 (10.1%), progressive multifocal leucoencephalopathy (PML) in 9 (4.8%), cerebral lymphoma in 1 (0.5%), and other conditions in 9 patients (4.8%). Seventy-three subjects (38.8%) showed focal brain lesions on initial computed tomography or magnetic resonance imaging, which were assessed prospectively. Positive predictivity for toxoplasmosis was 100% if multiple lesions occurred in combination with mass effect or contrast enhancement (23 patients), or if at least one space-occupying or enhancing lesion was located in the basal ganglia or the thalamus (26 patients). Solitary lesions with mass effect or contrast enhancement were seen in 26 patients and were caused by cerebral toxoplasmosis in 22 (84.6%). Eight of the 9 PML patients presented with one or more non-enhancing, non-mass lesions, although the predictive value of this pattern was low (47.1% for PML). Thus, in our epidemiological context, certain imaging findings in HIV-1-seropositive patients were highly predictive of cerebral toxoplasmosis. This may differ from findings from other parts of the world where cerebral toxoplasmosis may be less prevalent among HIV-1-infected individuals.

Relationship between striatal glucose consumption and copper excretion in patients with Wilson's disease treated with D-penicillamine.

In 12 patients with Wilson's disease treated with D-penicillamine (DPA), the regional cerebral metabolic rate of glucose consumption of the lentiform and caudate nucleus was analysed using the 18Fluorodeoxyglucose method and correlated with the clinical symptoms of the patients, the ceruloplasmin level, the serum level of free copper and the 24-h copper excretion. The more copper was eliminated, the higher was the basal ganglia glucose consumption. On the other hand, in seven patients who had been treated for more than 7 years a significant decline of the basal ganglia glucose consumption was observed, suggesting too low a maintenance dose of DPA.

Electrophysiological motor testing, MRI findings and clinical course in AIDS patients with dementia.

Thirty-three HIV-positive patients with clinical signs of dementia according to the 1991 AAN criteria underwent psychometric, electrophysiological and radiological examination and were compared with a group of normal healthy subjects and a cohort of clinically asymptomatic HIV-1-positive individuals of comparable education and social environment. Compared with the other groups, test performance was severely impaired in the demented patients. Results of motor testing and MRI revealed that subcortical structures were not exclusively affected, but most severely and early, thus characterizing the clinical feature in HIV-1-associated dementia. In demented patients a rapid deterioration was observed, leading to death within about 12 months on average, which is a markedly shorter survival time than described in the literature for non-demented HIV-1-positive individuals.