Tensiomyography and Statistical Analysis Based Muscle Change Detection in Multiple Sclerosis for Smart Healthcare.

The impact of demyelinization on muscle fiber changes and the type of changes in multiple sclerosis (MS) is very hard to estimate. One of the major problems of MS patients is muscle fatigue and decrease of muscle force in the range of 16-57%. The objective of this research work is to estimate various aspects of muscle changes at tibial muscle (mTA) level using a noninvasive method named as tensiomyography (TMG). TMG provides information about muscle functions in MS. This study includes 40 MS patients among which 18 are males (45%) and 22 are females (55%). They are divided in two subgroups: subgroup A and subgroup B. Subgroup A includes 20 MS patients without clinical decelable gait disorders and subgroup B includes 20 MS patients with clinical decelable gait disorders. Also, we have a control group that includes 20 healthy people with the same average age. Average age is 38.15 ± 11.19 y for MS patients and 39.34 ± 10.57 for healthy people. Evaluation measures include ADL score and EDSS scale. The ADL score is 0 for patients from subgroup A and 1 for patients from subgroup B. The EDSS score is 1 for subgroup A and 2.5 for subgroup B. This study confirms the importance of TMG based evaluation of muscle changes in MS patients. This smart healthcare system is also used for prediction of the muscle changes and muscle imbalance. Contraction time (Tc) recordings are used to detect the muscle fatigue which is a specific symptom of MS. The value of Tc for subgroup A is 45.8 ms and subgroup B is 61.37 ms for right side. Analysis of these two parameters such as Dm and Tc could define the muscle behaviour and help provide early information about the possibility of developing gait disorders. This smart TMG system analyses the muscle tone in the best possible way to predict the onset of any diseases which is an integral part of the smart healthcare system.

Functional muscle balance assessment in multiple sclerosis.

BACKGROUND: Chronic demyelinisation in multiple sclerosis (MS) involves changes in the muscle structure and development of motor disorders. OBJECTIVE: The aim of this research is to assess the muscle balance of thigh muscle in MS using a noninvasive method, to have information about the muscle status prior to the rehabilitation and to prevent muscle damage. METHODS: The studied group consisted of 20 patients: 9 men and 11 women, with a mean age of 42 years. The patients were diagnosed with MS in different stages. The clinical evaluation included clinical examination, neurological examination, functional evaluation by using the Hamilton score, the activity daily living (ADL) scale and the Kurtze (EDSS) scale. For the muscle assessment we used tensiomyography (TMG), an evaluation method for the functional potential of the muscle, depending on the muscle composition. The TMG parameters are displacement (Dm), contraction time (Tc) and sustain time (Ts) for biceps femoris (mBF) and rectus femoris (mRF). RESULTS: The value of Dm shows low values for both studied muscle groups, but closer to the normal value for mBF. The average normal Tc values for mBF are 30.25 ± 3.5 ms and 32.83 ± 4.5 for mRF. The values are low values for mRF and high for mBF. The normal values of Ts are not standard values and can be compared healthy individuals' values. These parameters could monitor the evolution and in our research have lower values for mRF. In the thigh, there was a significant difference in the Dm values, with higher values in mBF and also with higher values in the right lower limb. Analyzing the Ts results, we noticed a difference between the two muscle groups with a significant reduction in mRF, showing the inability to achieve anterior-posterior symmetry and the tendency to develop type I fibers at mBF level. CONCLUSIONS: Our study showed the presence of a structural and functional asymmetry explained by the tendency of increasing the tonus at mRF level in order to compensate the knee stability. We noticed a decrease in Tc value at the mRF level, but close to the value of the two lower limbs. TMG analysis revealed the asymmetry of the muscle composition at the level of the antagonist muscle groups of the thigh, with an increase in the percentage of type II fibers in the previous group, which became hyperton, and a decrease in the percentage of type I fibers in the posterior group.

Morphofunctional muscle changes influence on foot stability in multiple sclerosis during gait prediction: The rehabilitation potential.

BACKGROUND: Multiple sclerosis patients may suffer muscle changes that involve gait disorders of the kinetic and kinematic parameters also their gait may be clinically symmetrical or asymmetrical. OBJECTIVE: The aim of this study is to analyze how the muscle change, could affect the biomechanical parameters of foot stability during the gait, by disturb the motor control. METHODS: The study group consisted of 13 patients diagnosed with multiple sclerosis, presenting clinically detectable abnormal gait. The biomechanical evaluation included the foot axes and angles -external and internal rotation; the foot angle deviation from the gait direction; the subtalar angle. RESULTS: The values of the foot angle were between -10.74∘ to 26.38∘ for the left foot and between -11.16∘ to 30.04∘ for the right foot. The foot axis angle is the axis of the foot in relation to the gait direction, and the subtalar angle is in relation to the vertical axis of the foot. The rotation of the right foot into pronation during the initial contact phase was followed by supination in the semi-support phase, to return to the neutral position during the propulsion phase, which meant being in free zone of minimal risk. CONCLUSIONS: Biomechanical analysis of the foot angle and of subtalar angle in the patients with multiple sclerosis allows us to objectify the existence of a right-left asymmetry, the behavior ankle-foot during the gait. At the same time this evolution is closely correlated with the contact surface that tends to increase, which means involving the reflex mechanisms that place the foot in the zone of minimum risk and assure the stability of the body.

Morphofunctional changes in distribution of pressure center in multiple sclerosis.

INTRODUCTION: Gait evaluation and assessment of motor performance are of utmost importance in the clinical management of multiple sclerosis (MS). A new approach to the analysis of static and dynamic balance of MS patients is the use of complex biomechanical analysis that includes an analysis of the distribution of the center of pressure (DCP) and loading, measured by using the pressure and force platforms. PATIENTS AND METHODS: The study was conducted on a total of 18 patients with MS, with the mean age of 41.2 years old, divided into two groups, according to the presence of clinically detectable gait disturbances. The biomechanical analysis that included the assessment of the loading and DPC was performed using the platform of force distribution. DPC represented the center of all the forces applied and its value could appreciate the mediolateral stability, hence the pronation or, respectively, the supination. Group 1, consisting of 12 patients with MS with clinically detectable gait disorders, including six men and six women, and group 2, of six MS patients without clinically detectable gait disorders, including two men and four women. RESULTS: For group 1, the center of pressure had a left-right asymmetric distribution, and also an anterior-posterior one. There was a predominant distribution at the medial heel, at metatarsals 1-3 and at the hallux. For group 2, the analysis of the plantograms recorded in our study indicated a tendency of the distribution of the pressure center in the metatarsals 2, 3 and less in the heel. CONCLUSIONS: The analysis of the loading and distribution of the pressure center was important not only to appreciate the static equilibrium disorders but also to appreciate how these disorders affected the gait initiation, since the patients suffered from anterior-posterior and mediolateral disorders, which produced spatial and temporal distortion preventing gait initiation. In the study of pressure and force, we noticed a predominant distribution on the lateral region of the heel, explained by an attempt of the body to compensate the disorders of balance and orientation of the reaction force of the ground to normalize the gait.

The correlation between insulin-like growth factor with glycemic control, glomerular filtration rate, blood pressure, hematological changes or body mass index in patients with type 2 diabetes mellitus.

Insulin-like growth factor (IGF) family is made up of two polypeptides, IGF-I and IGF-II, six specific binding proteins (IGFBPs 1-6) and specific receptors. IGF-I is involved in the regulation of growth and cellular proliferation and has a similar structure to insulin. The major IGF transport function is attributed to IGFBP-3. Some studies have highlighted the association between IGF and diabetes. The aims of this study were to analyze the correlation between IGF with glycemic control, glomerular filtration rate (GFR), blood pressure, hematological changes or body mass index (BMI) in patients with type 2 diabetes mellitus (T2DM). Thirty patients with T2DM and thirty non-diabetic control patients were included in this study. Clinical, anthropometric, biochemical parameters and morphology of blood smear were recorded. Blood pressure was determined by mercury sphygmomanometer. The anthropometric measurement included BMI. The biochemical parameters included fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), GFR, serum IGF-I, IGFBP-3 levels. The IGF-I÷IGFBP-3 ratio was evaluated. The plasma glucose was determined enzymatically, HbA1c was determined by high-performance liquid chromatography (HPLC) and GFR was calculated automatically. IGF-I was measured by immunoradiometric assay (ELISA - enzyme-linked immunosorbent assay) and IGFBP-3 by sensitivity immunoassay. For the analysis of the morphology of blood smear, May-Grünwald-Giemsa (MGG) was used as staining technique. The microscopic examination was performed initially with the objectives of 10×÷20× and subsequently with an immersion objective of 100×. Image acquisition was done after the examination of the preparations obtained with a 40× objective, using Image Pro Plus 6.0 software. In the present study, we observed that T2DM leads to an increase in the IGF-I and IGFBP-3 levels. No relationship was obtain between IGF-I, IGFBP-3 levels and IGF-I÷IGFBP-3 ratio with neither parameters studied. The difference of serum IGF-I and IGFBP-3 levels between patients with T2DM and subjects without diabetes showed that IGF-I may be a useful marker for diabetes mellitus and IGFBP-3 for possible complications of this affection.

Prediction of motor disorders in multiple sclerosis using muscle change structure assessment.

INTRODUCTION: The neuropathogenesis of multiple sclerosis (MS) lesions has been explained by several mechanisms, which emphasize the unpredictable nature of these lesions. The aim of this study is to present the neuromuscular changes in MS at the patients without gait or motor disorders using a noninvasive method named tensiomyography (TMG). PATIENTS AND METHODS: The studied group included a number of seven MS patients without clinically detected gait disorders, with mean age of 33.28 years (min. 22 years-max. 60 years), diagnosed with progressive multiple sclerosis with relapses - three patients and with relapsing-remitting multiple sclerosis (RRMS). They have been evaluated using clinical, functional scales for evaluation and neuromuscular assessment using TMG parameters (displacement Dm, contraction time - Tc, delay time - Td, supporting time - Ts, relaxation time - Tr), for rectus femoris (mRF). RESULTS: The group with MS patients recorded functional asymmetries with higher values in the left lower limb. We determined Tc values lower than the minimum normally required, which meant that in the group with MS there was an increase in the percentage of type II fibers. Other TMG parameters show important difference between left and right side even if they do not have gait disorders. DISCUSSION AND CONCLUSIONS: These patients with MS underwent modifications in their muscle tone, muscle strength and other changes related to the presence or absence of muscle atrophy. The muscle tone could be affected by the muscle atrophy or hypertrophy. In conclusion, this type of assessment performs the non-invasive assessment of contractile properties of the muscles, without the integration of the tendon properties, joint mechanics or connective tissue in the mechanical response to muscle deformation produced by electrical stimulation.

Complex assessment in progressive multiple sclerosis: a case report.

UNLABELLED: The study presents the case of a patient with progressive multiple sclerosis in relapses (PPMS) and proposes a comprehensive neuromuscular and biomechanical evaluation in order to achieve a predictive picture of gait evolution and balance disorders with disease progression. PATIENT AND METHODS: The evaluation included: clinical, functional and neuromuscular evaluation by tensiomyography (TMG) and biomechanics (by RSscan platform force). Elements evaluated included the calf muscle groups (tibialis anterior and gastrocnemius) and the following parameters were assessed from neuromuscular point of view: contraction time, sustain time, delay, relax time and displacement amplitude after electrical stimulation. Biomechanically, we assessed the subtalar angle, foot loading in metatarsian area, foot balance and pressure center distribution. RESULTS AND CONCLUSIONS: From neuromuscular point of view, we concluded that the right anterior tibial muscle developed compensatory muscle fibers resistant to fatigue. TMG analysis can estimate the possibility of developing gait disorders even in the absence of visible clinical manifestations. We also noted an increased muscle tone in the muscles of bilateral twins. Biomechanical evaluation revealed a symmetrical, abnormal gait, explained by the difference in the angle of left and right foot and in subtalar angle, which expresses the degree of coordination and control of foot gait initiation and execution. In this context, there is an exorotation of both feet.

Analysis of neuromuscular parameters in patients with multiple sclerosis and gait disorders.

UNLABELLED: Gait is a motor activity that requires understanding the dynamics and functional anatomical elements that make possible its cyclical conduct. Patients with multiple sclerosis record impaired balance and gait due to the process of demyelination, disorders that can be estimated by quantifying neuromuscular and cortical parameters. The aim of this paper is to present both an analysis of these parameters in the thigh muscles and an evaluation of cortical parameters obtained by visual evoked potentials (VEP). PATIENTS AND METHODS: The study was conducted on a group of 13 patients (mean age 38 years) with multiple sclerosis (MS), who had clinically detectable gait disturbance. Evaluation methods used were tensiomyography (TMG) and VEP, the monitored parameters were: contraction time (Tc), stance time (Ts), displacement (Dm), if TMG in the two muscle groups of the thigh (biceps femoris and right femoris), and if VEP the assessed waves were N75, P100, N135-145. RESULTS: There were estimated the average values of latency and duration of the three analyzed waves in VEP, the values of wave N135-145 were far higher than physiological values. In terms of TMG values, they results indicate the existence of a clear right-left functional asymmetry. DISCUSSION AND CONCLUSIONS: Analyzing these results, we note an increase in the muscular tone of the groups studied, a functional asymmetry agonist/antagonist, low speed response to stimulus. Regarding VEP wave parameters, we find significant variations of these waves' latencies, particularly of P100 wave, while the duration of these waves did not register significant figures. In conclusion, we can emphasize a change in muscle structure with predominantly type I muscular fibers and inter-neuronal connections between areas of the association to substitute the lesions occurred in specific areas.

Plasma levels of glucose and insulin in patients with brain tumors.

In the last years there were many authors that suggest the existence of an association between different components of metabolic syndrome and various cancers. Two important components of metabolic syndrome are hyperglycemia and hyperinsulinemia. Both of them had already been linked with the increased risk of pancreatic, breast, endometrial or prostate cancer. However the correlation of the level of the glucose and insulin with various types and grades of brain tumors remains unclear. In this article we have analysed the values of plasma glucose and insulin in 267 patients, consecutively diagnosed with various types of brain tumors. Our results showed no correlation between the glycemia and brain tumor types or grades. High plasma levels of insulin were found in brain metastasis and astrocytomas while the other types of brain tumors (meningiomas and glioblastomas) had lower levels of the peptide. The levels of insulin were also higher in brain metastasis and grade 3 brain tumors when compared with grade 1, grade 2 and grade 4 brain tumors.

The dedifferentiation of neuroendocrine tumor metastases: myth or reality?

Dedifferentiation is a process that may be found in metastasis from the neuroendocrine tumors. We present the case of a female within the seventh decade of life incidentally diagnosed with a mature teratoma with element of cartilages, bronchia, mucinous glands, and a poorly differentiated neuroendocrine carcinoma (Ki67 of 30%). After six months of chemotherapy and another six months of disease free interval, a metastasis of the great omentum was removed. The dedifferentiation was diagnosed based on much higher Ki67 (of 70%). The loss of estrogen receptor of 40% from the initial site to 3% into metastasis indicates an exclusive neuroendocrine aggressive pattern. The ovarian carcinoid is a rare situation, and metastasis to the great omentum with dedifferentiation is even seldom.

The poor prognosis factors in G2 neuroendocrine tumor.

BACKGROUND: The G2 neuroendocrine tumors (NET) or well-differentiated neuroendocrine carcinomas (2010 WHO Classification of Tumours of the Digestive System) embrace different types of evolution despite the fact that they actually are included in the same group of prognosis based on mitotic count and the Ki-67 proliferation index. AIM: We studied the pathological and clinical aspects in patients with G2 NET. MATERIALS AND METHODS: This is a retrospective pilot observational study in patients admitted between January 2008 and January 2013 in "Constantin I. Parhon" National Institute of Endocrinology, Bucharest, Romania. They were evaluated based on the pathological report, imagistic scan, and neuroendocrine markers. RESULTS: Nine patients (female/male ratio: 5/4) with G2 NET were included (mean age at diagnosis 54.11 years). Surgery was performed in 66.66% of cases. 44.44% of tumors had unknown origin. 22.22% of patients had negative immunostain for chromogranin A. Synaptophysin was positive in all cases. Neuronal specific enolase (NSE) was performed in 44.44% of cases and it was positive in all these situations. 88.88% of patients had high neuroendocrine markers. Multiple tumors were found in two cases (follicular thyroid adenoma, and a carcinoma of the port vein, respective bilaterally pheochromocytomas). The youngest patient (39-year-old) had atypical onset with bilateral adrenal tumors (positive for CHROMO, EMA, CK-19, CK-20, negative for SOMATO, CK-7, S-100, glucagon, CD57, and a Ki-67 of 15%). Death was registered in two cases, both with bone metastases. DISCUSSION: Some poor prognosis factors may be taken into account as lack of CHROMO immunostain, young age at diagnosis, genetic background, and lack of therapy options as surgery. Larger databases will provide more information. CONCLUSIONS: It is possible that the G2 NET group of tumors actually includes some different subtypes or in fact, a late diagnosis of the tumor might be associated with a poor diagnosis.

Tropomyosin-receptor-kinases signaling in the nervous system.

ABSTRACT: The development and function of the nervous system is dependent on many growth factors and their signaling. Tropomyosin-receptor-kinase receptor family controls synaptic strength and plasticity in the mammalian nervous system. Dysregulation of Tropomyosin-receptor-kinase receptors signaling can lead to neural developmental disorders and has been reported in certain diseases of the nervous system. Apart from their role in the nervous system, these tyrosine kinase receptors are also involved in cancer biology. Tropomyosin-receptor-kinases and their ligands, neurotrophins, are also involved in neural precursor stem cells differentiation. This review focuses on Tropomyosin-receptor-kinases, the most abundant receptors in mammalian nervous system.

Biomechanical disorders of foot in multiple sclerosis.

Multiple sclerosis (MS) has a multifactorial etiology located at the interaction point of environmental factors--nutritional, geographic, infectious, etc.--with genetic factors, which confers susceptibility to disease or alters its development. This research presents a case study focused on complex assessment of a patient using clinical and functional assessment, biomechanical gait evaluation using RSScan force plate. Biomechanical parameters (contact area, load, impulse, force, pressure, foot balance) are the parameters that we obtain after force plate measurements. Analyzing the results of the functional assessment, it is found an anatomical functional abnormality with a tendency to increase. Biomechanical tests show an asymmetric gait due to the impact of neurological disorders generated in the proprioceptive system. Global analysis of values (surface contact, pressure, force, load, impulse, active contact area) indicates the fact that there is a tendency to develop a higher pressure in the anterior-medial region of the plant in an attempt to maintain balance. It is a tendency to increase the active contact area in the forefoot region; this increase is explained by the body tendency to develop compensatory mechanisms to maintain balance.

Morphofunctional aspects of lower limb in multiple sclerosis.

Gait, as an expression of the locomotive system, needs a complex biomechanical analysis, which allows the description of multiple sclerosis (MS) specific patterns, MS patients having a polymorphism of motion patterns. The studied group consisted of 13 MS patients with gait disorders, average age of the group was of 36 years. The evaluation of the subjects comprises: clinical evaluation (anamnesis, neurological examination), paraclinical evaluation (MRI), functional evaluation, neuro-physiologic evaluation and biomechanical evaluation. Biomechanical examination was completed using the force and pressure-measuring platform of plantar pressure distribution Footscan Scientific Version, RSscan. The studied parameters were: contact area, active contact area, heel rotation, foot balance, foot angle. The evaluated zones during a gait cycle were: the heel, medial foot, antefoot. Although the analysis of contact area in the lateral foot did not show any significant differences between the right and the left foot, it nonetheless underlined a major difference in the expression of maximum and minimum values, which meant that MS patients with clinically detectable gait disorders had a tendency to increase contact area to maintain balance. Examining the foot positions in relation to the movement direction and to the foot vertical axis, we noticed the existence of certain elements indicating an orientation tendency of the foot. This tendency had to be related to neutral position (corresponding to anatomical position) of the foot. We also noticed a foot deviation in abduction, associated with visible pronation and decrease of the contact area corresponding to medial plantar zone.

The immunohistochemistry aspects in two cases of neurofibromatosis-associated abdominal tumors.

Type 1 neurofibromatosis associates various abdominal tumors as gastrointestinal stromal tumors, duodenal or pancreatic carcinoid, and adrenal tumors like pheochromocytoma. We present the immunohistochemistry report in two cases with different profile regarding the evolution. One case is a 7th decade women diagnosed with unilateral pheochromocytoma and GISTs, with a good prognosis after surgery. The other case is a 41-year-old male diagnosed with duodenal metastatic somatostatinoma after an intestinal occlusive syndrome and later the hormonal profile leaded to the diagnosis of pheochromocytoma. The patient had a fulminate evolution within six months from diagnosis.

Neuromuscular assessment in the study of structural changes of striated muscle in multiple sclerosis.

UNLABELLED: The aim of this research is to present the results of neuromuscular assessment using tensiomyography (TMG) in multiple sclerosis for prediction the muscle changes. This study consists of 20 patients, selected conform to certain criteria. Thus, according to diagnosis and MS level, the studied group was divided into two subgroups: subgroup A, consisting of 13 MS patients with clinically detectable gait disorders, and subgroup B, made up of seven MS patients without clinically detectable gait disorders. TMG determines the diagnosis of a certain muscular type and muscular status÷condition (fatigue, stress influence on the body, etc.), the diagnosis of a functional muscular symmetry. The investigation has been performed on the shank muscles. The parameters evaluated through TMG were: contraction time (Tc) and the amplitude of muscular displacement in transverse direction - Dm (mm) a parameter which is also correlated with Tc values and depends on the flexibility of muscular tissue. RESULTS: Dm in the case of gastrocnemius muscles (mG) data analysis shows an evolution of functional bilateral right-left asymmetry, which is more pronounced in subgroup A. At the level of posterior shank, Dm values in subgroup A are lower, which means that patients in subgroup A have a higher muscular tone and a maximum response to stimulation. Concerning Tc values, this parameter indicates muscular fatigue at the level of anterior tibialis. CONCLUSIONS: TMG, besides classical methods of paraclinical investigation, improves data generation, standardization, identifies correlations, which may facilitate a precocious diagnosis in morphofunctional changes evolution at muscular level at MS patients.