Longterm course of neuropsychological symptoms and ME/CFS after SARS-CoV-2-infection: a prospective registry study.

A significant proportion of patients after SARS-CoV-2 infection suffer from long-lasting symptoms. Although many different symptoms are described, the majority of patients complains about neuropsychological symptoms. Additionally, a subgroup of patients fulfills diagnostic criteria for ME/CFS. We analyzed a registry of all patients presenting in the out-patients clinic at a German university center. For patients with more than one visit, changes in reported symptoms from first to second visit were analyzed. A total of 1022 patients were included in the study, 411 of them had more than one visit. 95.5% of the patients reported a polysymptomatic disease. At the first visit 31.3% of the patients fulfilled ME/CFS criteria after a median time of 255 days post infection and and at the second visit after a median of 402 days, 19.4% still suffered from ME/CFS. Self-reported fatigue (83.7-72.7%) and concentration impairment (66.2-57.9%) decreased from first to second visit contrasting non-significant changes in the structured screening. A significant proportion of SARS-CoV-2 survivors presenting with ongoing symptoms present with ME/CFS. Although the proportion of subjective reported symptoms and their severity reduce over time, a significant proportion of patients suffer from long-lasting symptoms necessitating new therapeutic concepts.

Recruitment and inclusion procedures as "pain killers" in clinical trials?

BACKGROUND: Recruitment and inclusion procedures in clinical trials are time critical. This holds particularly true for studies investigating patients with fluctuating symptom patterns, like those with chronic neck pain. In a feasibility study on neck pain, we found a clinically relevant decrease in pain ratings within the recruitment period. This paper analyses the phenomenon and gives recommendations for recruitment procedures in clinical trials on pain. METHODS: Changes in pain intensity scores of 44 chronic neck pain patients (6 males and 36 females; mean age: 45.3±13.2 years) between the first telephone contact and baseline assessment were analyzed. Inclusion criterion was a mean pain intensity of ≥40 on a 0-100 numerical rating scale during the last three months. Statistical analyses were performed using ANOVA and parametric/non-parametric correlation coefficients. RESULTS: Average pain intensity score decreased significantly from 60.3±13.3 at telephone interview to 38.1±21.7 at baseline assessment. This represents a relative change of 36.8%. A weak but significant negative correlation was found between number of days between assessments and pain rating differences. There was a positive correlation between change of pain intensity and the pain level at the first contact, indicating that the decreased pain ratings over time were also dependent on the initial pain rating. CONCLUSIONS: The clinically significant changes in pain intensity were weakly related to waiting time and moderately dependent on initial pain intensity, suggesting regression to the mean. The natural course of the disease and the Hawthorne effect are also discussed as contributing factors.

Laser heat hyperalgesia is not a feature of non-specific chronic low back pain.

BACKGROUND: Based upon studies using mechanical pin-prick, pressure, electrical or heat stimuli applied to painful and/or pain-free parts of the body, chronic low back pain (CLBP) has been shown to be associated with generalized and enhanced pain sensitivity and altered brain responses to noxious stimuli. To date, no study examined the processing of noxious laser heat pulses, which are known to selectively excite thermal nociceptors located in the superficial skin layers, in CLBP. METHODS: We studied laser heat pain thresholds (LHPTs) and nociceptive laser-evoked brain electrical potentials (LEPs) following skin stimulation of the pain-affected back and the pain-free abdomen using noxious laser heat stimulation in 16 CLBP patients and 16 age- and gender-matched healthy controls (HCs). RESULTS: We observed no statistically significant differences in LHPTs between CLBP patients and HCs, neither on the back nor on the abdomen. Furthermore, we found no evidence for altered brain responses between CLBP patients and HCs in response to stimulation of the back and abdomen in single-trial latencies and amplitudes of LEP components (N2, P2). CONCLUSION: The results are in contrast to previous studies showing hypersensitivity to different experimental noxious stimuli (e.g., contact heat). We argue that these discrepancies may be due to low spatial and temporal summation within the central nervous system following laser heat stimulation. Our results indicate important methodological differences between laser heat and thermode stimulation that should be taken into account when interpreting results, such as from thermal quantitative sensory testing.

[Severe and moderate haemophilia under prophylactic replacement treatment--maximal knee extensor and flexor torque of children and adolescents]. / Schwere und mittelschwere Hämophilie unter prophylaktischer Substitutionstherapie. Maximale Drehmomente der Knieextensoren und Knieflexoren bei Kindern und Jugendlichen.

UNLABELLED: Due to its influence on haemophilic arthropathy, the evaluation of knee extensor (K(Ext)) and flexor (K(Flex)) torques plays an important role in the preventive and rehabilitative context of haemophilia. Thus, the present study aimed at investigating maximal static torque (M(Max)) of K(Ext) and K(Flex). 14 boys with haemophilia (8 severe, 6 moderate; age: 11.7 ± 2.8 years; prophylactic treatment > 5 years) and 14 healthy carefully pair-matched controls (age: 11.5 ± 2.7 years) were separately measured for the left and right leg for M(Max). Furthermore, the ratio K(Flex)/K(Ext )was calculated and the joint situation assessed using the Haemophilia Joint Health Score. RESULTS: No significant group-effect was observed for M(Max) of the K(Ext) and K(Flex) as well as for the ratio K(Flex)/K(Ext) (p>0.05). Despite significant higher joint scores in haemophilic children compared to their healthy controls (p<0.01), patients merely showed minor joint impairments. CONCLUSION: Children and adolescents with severe and moderate haemophilia under prophylactic replacement treatment with a good joint status showed comparable maximal strength performance of relevant knee muscles compared to their healthy peers.

Ankle muscle activation in people with haemophilia.

Since normative surface EMG (SEMG) values for muscles acting at the knee joint are available for people with haemophilia, increasing interest is noticeable for other joints affected by haemophilic arthropathy. Adequate activity of shank muscles is an important key for appropriate postural control. The aim of this study was to determine differences in muscle activation patterns of lower leg muscles between people with and without haemophilia during upright standing. SEMG of tibialis anterior (TA), fibularis longus (FL), lateral (LG) and medial (MG) heads of gastrocnemius, and soleus (SO) muscles of both sides were recorded in 25 haemophilic patients (H) and 25 non-haemophilic control subjects (C) while standing on even ground. The Gilbert-Score was used to assign sides to major (H-MA) and minor (H-MI) affected ankle joints in H. To normalize the SEMG amplitudes, amplitude ratios (percentage of cumulated activity) were calculated. Compared to controls, TA ratios showed higher and MG reduced levels in both H groups (P < 0.01). In the H-MA subgroup of H, FL also joined the TA behaviour whereas SO had similar activation direction as MG. Although possible descending influences from the knee joints cannot be excluded, this can be interpreted as a compensational mechanism due to the severity of the orthopaedic status of the ankle, which with increasing heaviness is accompanied by reduced plantar flexion capability. However, ankle joint integrity appears to be reduced in H, with TA and MG seeming to play key roles for neuromuscular control of upright posture.

[Is there a correlation between back pain and stability of the lumbar spine in pregnancy? A model-based hypothesis]. / Besteht ein Zusammenhang zwischen Rückenschmerz und der Stabilität der lumbalen Wirbelsäule in der Schwangerschaft? : Eine modellbasierte Hypothese.

During pregnancy approximately 50% of women suffer from low back pain (LBP), which significantly affects their everyday life. The pain could result in chronic insomnia, limit the pregnant women in their ability to work and produce a reduction of their physical activity. The etiology of the pain is still critically discussed and not entirely understood. In the literature different explanations for LBP are given and one of the most common reasons is the anatomical changes of the female body during pregnancy; for instance, there is an increase in the sagittal moments because of the enlarged uterus and fetus and the occurrence of hyperlordosis.The aim of this study was to describe how the anatomical changes in pregnant women affect the stability and the moments acting on the lumbar spine with the help of a simplified musculoskeletal model.A two-dimensional musculoskeletal model of the lumbar spine in the sagittal plane consisting of five lumbar vertebrae was developed. The model included five centres of rotation and three antagonistic pairs of paraspinal muscles. The concept of altered acting torques during pregnancy was explored by varying the geometrical arrangements. The situations non-pregnant, pregnant and pregnant with hyperlordosis were considered for the model-based approach. These simulations were done dependent on the stability of the erect posture and local countertorques of every lumbar segment.In spite of the simplicity of the model and the musculoskeletal arrangement it was possible to maintain equilibrium of the erect posture at every lumbar spinal segment with one minimum physiological cross-sectional area of all paraspinal muscles. The stability of the musculoskeletal system depends on the muscular activity of the paraspinal muscles and diminishing the muscular activity causes unstable lumbar segments.The relationship between the non-pregnant and the pregnant simulations demonstrated a considerable increase of acting segmental countertorques. Simulating an increased lordosis for the pregnant situation in the sagittal plane substantially reduced these acting countertorques and therefore the demand on the segmental muscles.It is assumed that hyperlordosis is a physiological adaptation to the anatomical changes during pregnancy to minimize the segmental countertorques and therefore the demand on the segmental muscles.Further, it can be expected that an enhanced muscle activity caused by selective activity of lumbar muscles increases the stability of the lumbar spine and may improve the situation with LBP during pregnancy.

[Altered hip muscle activation in patients with chronic non-specific low back pain]. / Veränderte Beckenmuskelaktivierung bei Patienten mit chronischem nichtspezifischem Rückenschmerz.

BACKGROUND: The aim of this study was to examine postural control in patients with chronic non-specific low back pain (CNRS). Furthermore the influence of visual information (eyes open versus eyes closed) was analyzed. MATERIAL AND METHODS: A total of 8 patients with CNRS and 12 healthy control subjects were examined. Surface electromyography (SEMG) recordings were made from 5 trunk and 5 lower limb muscles as well as one hip muscle during application of distal lateral perturbation. RESULTS: Healthy controls (mean ± standard deviation: 96.42±64.77 µV) showed a significantly higher maximum amplitude of the gluteus medius muscle in comparison to patients with CNRS (56.29±39.63 µV). Furthermore activation of several lower limb muscles was found to be dependent on visual information. CONCLUSION: Patients showed an altered reflex response of the gluteus medius muscle which could be associated with reduced hip stability.

SEMG activation patterns of thigh muscles during upright standing in haemophilic patients.

Although electromyography (EMG) is a common method to evaluate muscle activity, studies utilizing EMG in haemophilic patients are rare. The haemophilic arthropathy, resulting in altered afferent information is expected to cause disturbed activation and inter-muscular coordination patterns in haemophilic subjects. The aim of this study was to determine differences of selected knee muscles between haemophilic patients and non-haemophilic subjects during upright standing. Surface EMG (SEMG) amplitudes of rectus femoris, vastus medialis (VM), vastus lateralis (VL) and biceps femoris (BF) muscles of both sides were measured in 27 haemophilic patients (H) and 26 control subjects (C) while standing on an even surface. Data from both sides were pooled in C, but data of H were subdivided further according to major (H-MA) and minor (H-MI) affected joints. To normalize the data, amplitude ratios (percentage of cumulated activity) were calculated as well. Regardless of whether H-MA or H-MI was compared with C, amplitudes of all extensor muscles reached significantly higher levels in H (P < 0.05). SEMG amplitude ratios also differed between H and C. Independent of subgroup, BF showed significantly reduced activation ratios (P < 0.01). Only the ratios of VM and VL of H-MA could replicate the observed amplitude differences to C (P < 0.05). These findings show that while standing, haemophiliacs maintain the necessary stability demands through increased extensor activities and modulated coordination patterns. Although all thigh muscles of haemophiliacs are characterized by distinct atrophy, increased amplitude levels could be proved for the knee extensor muscles only. Therefore, general atrophy-related effects cannot explain these results.

Healthy humans use sex-specific co-ordination patterns of trunk muscles during gait.

Human gait patterns differ considerably between the sexes. Therefore sex specific trunk muscle activation patterns can be expected. Healthy volunteers of both sexes (51 women, 55 men) walked on a treadmill at speeds from 2 to 6 km/h. Surface electormyography was recorded from five pairs of trunk muscles. Grand averaged root mean square (rms) curves and amplitude normalised curves were calculated. Mean amplitudes and relative amplitudes were calculated as well. Mean amplitudes as well as relative amplitude levels were not generally sex specific, but differed for single muscles. Grand averaged rms curves of all investigated muscles differed between sexes. At low walking speeds, differences mostly originated from mean amplitude level differences, alternating between sexes. At higher walking speeds, amplitude curves became more phasic, differences again alternated between sexes. Therefore, trunk muscle co-ordination during gait is sex-specific. Any interpretation of trunk muscle co-ordination patterns during gait requires sex specific normatives.

Physical training increases isometric muscular strength and proprioceptive performance in haemophilic subjects.

Sufficient muscular strength and proprioception lessen the risk of joint damage, however, both are impaired in haemophilic subjects. The aim of the study was to investigate proprioceptive performance and isometric muscular strength before and after a specialized training in haemophilic subjects (H) compared with two groups of control subjects (C). Nine subjects with severe haemophilia A, and eight 'active' C (AC) without haemophilia took part in a physical training programme over a 6-month period. Eleven 'passive' C (PC) were requested to avoid any additional training during this period. Proprioceptive performance and isometric strength were determined before and after the training programme. The maximal isometric muscular strength in the legs, bilaterally measured by knee extensor (and leg press) was increased (P < 0.05) by 34% (29%) after training in the H and by 20% (28%) in the AC groups while remaining unchanged in the PC group. The performance in one-leg-stand tests after training was increased (P < 0.05) in the H and AC groups. An improvement of angle reproduction of 20 degrees and 40 degrees (P < 0.05) in the H compared with the PC groups was seen in the tests. Quantitative sensory testing by the tuning fork showed an increase (P < 0.05) in performance of both H and AC groups. The results of the present study confirm that specific sports therapy focused on proprioceptive function and accompanied by gentle strength training with low resistance and 20-25 repetitions is able to increase proprioceptive performance and muscular strength with a minimal stress to the joints. It is strongly recommended that specialized sports therapy be included as an integral component of the complete treatment regimen of haemophilic subjects.

Enhanced gametocyte production in Fansidar-treated Plasmodium falciparum malaria patients: implications for malaria transmission control programmes.

Gametocytes are the agents in malaria transmissible between the vertebrate host and the mosquito vector, and an increase in their incidence would be expected to have a corresponding impact on the prevalence of malaria, particularly in areas of high transmission. The purpose of this study was to determine whether there is an association between the type of antimalarial drug administered and the production of gametocytes. Two commonly used drugs, Fansidar and chloroquine, were compared in this respect. A total of 94 people (mean age +/- s.d. 16.94 +/- 19.03 years), from a highly endemic malaria area of Zambia, were treated with either Fansidar or chloroquine (Fansidar, n = 46, chloroquine, n = 48). The percentages of gametocytes generated after treatment were 23.9 for Fansidar and 6.2 for chloroquine. A 2 x 2 table analysis of the data shows that the P values, both by chi 2 and Z analysis, were less than 0.02, suggesting a statistically significant difference in the propagation of gametocytes between the two treatment groups. There was no significant difference in the quantitative gametocyte count per 200 white blood cells (Fansidar, 7.5 +/- 8.57; chloroquine, 4.5 +/- 1.64; P > 0.10), probably because of the small size of the 'gametocyte' sample (n = 14).

Tumour necrosis factor alpha in uncomplicated malaria in young adults.

The purpose of this study was: 1) to measure tumour necrosis factor alpha (TNF) in the plasma of Plasmodium falciparum infected subjects; and 2) to correlate the presence of TNF to symptomatology. Plasma from 77 malaria infected individuals (with malaria parasites) were assayed for TNF by ELISA. The mean age of the subjects under study was 16.36 +/- 0.80 (mean +/- SEM) years. Thirty-nine (51%) subjects had measurable plasma TNF. Taking symptomatology into account, 10 (59%) of the 17 asymptomatics and 29 (48%) of the 60 symptomatics had measurable plasma TNF. A risk ratio of 0.9 was obtained for the association between the detection of plasma TNF and the presence of symptoms. In plasma from 13 healthy controls no TNF was detected. The results suggest that if TNF plays a negative role in the pathogenesis of malaria, it must be in the presence of other predisposing factors.

Antimalarial drug sensitivity patterns in the western province of Zambia. Implications for the management of primary health care (PHC).

The management of acute malaria consists of chemotherapy aimed at restoring the normal function of all organs. Appropriate treatment is dependent upon extensive knowledge of the drug sensitivity patterns of the malaria parasites in the area. This is also important for chemoprophylaxis. Drug sensitivity patterns and recrudescence rates for Mongu (Western Province in Zambia) are suggestive of a likely increase in resistance to both chloroquine and sulfadoxine-pyrimethamine (Fansidar). We found RI (19.4%), RII (1.5%) and RIII (4.4%) resistance to chloroquine and RII (4.3%) resistance to Fansidar. This calls for careful consideration of treatment schedules, legislation pertaining to the distribution of drugs in the general public and alternative antimalarial control strategies.