Symmetrical Limb Research Articles

Branched-Chain Amino Acids Deficiency Promotes Diabetic Neuropathic Pain Through Upregulating LAT1 and Inhibiting Kv1.2 Channel.

Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

Reliability of the Hop Test and Asymmetry Index in University Athletes: A Cross-Sectional Study Assessing Injury Risk

This study aims to assess the reliability of hop tests among healthy university athletes and to identify leg asymmetries through these assessments. A cohort of 212 university athletes, active in sports, participated in the study. Hop tests, comprising four distinct procedures, were administered to evaluate lower extremity strength. The hop tests demonstrated high reliability, with reliability coefficients ranging from 0.704 to 0.990. Examination of asymmetry indices revealed mean values of 101.07%, indicative of symmetrical limb function among participants. Gender-based differences were notable in hop test results, particularly in the crossover hop test, which showed significant asymmetry (p

Apert syndrome: modern aspects of diagnosis and treatment

The purpose of this review is to raise awareness of medical professionals about the features of the clinical picture, the possibilities of diagnosis (including prenatal) and therapy of patients with Apert syndrome to further improve the prognosis and improve the quality of life. Acrocephalosyndactyly is a group of rare congenital syndromes characterized by the presence of acrocephaly, craniofacial anomalies, syndactyly of the hands and feet. According to the literature, the most common form of аcrocephalosyndactyly is Apert syndrome (acrocephalosyndactyly type I, Apert syndrome, ICD 10 Q 87.0, OMIM 101200). This is a genetic disease inherited by an autosomal dominant type. CA is caused by a mutation of the fibroblast growth factor receptor type 2 gene (FGFR2) located on the long arm of chromosome 10, which leads to increased bone metabolism and impaired bone synthesis. The frequency of Apert syndrome is about 15 cases per 1,000,000 live births. Wheaton first reported this pathology in 1894, and in 1906 the French pediatrician Eugene Apert published a series of nine clinical cases with a characteristic triad of symptoms. Apert syndrome is characterized by craniosynostosis, bilateral symmetrical limb syndactyly and dysmorphic facial features. Hypoplasia of the upper jaw and bicoronal synostosis are two noticeable craniofacial defects that lead to a flat, deepened appearance of the forehead and the middle part of the face. Hypertelorism and excessive orbitality, low-set ears, flat nose and cleft palate are often found. Cardiovascular, neurological and genitourinary abnormalities may be present. Diagnosis is based on clinical criteria and molecular genetic testing. There is a possibility of prenatal detection of Apert syndrome.

An Evaluation of Variations in the Carpal Tunnel Dimensions of Adult Subjects in a Hospital-Based Population: An Ultrasonographic Cross-Sectional Study.

Background The carpal tunnel is a groove that spans the palm as a 'U.' The ulnar and radial sides of the wrist are made up of the scaphoid tubercle and trapezium while the palmar aspect is made up of carpal bones. Our study aimed to see whether there were differences in carpal tunnel size between men and women. Material and methods The study was conducted on 65 healthy adults, 13 (20%) were males and 52 (80%) were females (both non-pregnant and pregnant). Inclusion criteria were healthy adults and bilaterally symmetrical limbs. Exclusion criteria were chronic disease, diabetes, hypertension, immunological disorders, any visible abnormalities, and a history of upper extremity pain on either side. A high-resolution ultrasound machine with a linear transducer was used to perform an ultrasound scan of the carpal tunnel. The anteroposterior dimension was measured at the midline, or along the axis of the middle finger, and the transverse diameter was measured at the midpoint of the flexor retinaculum. The cross-sectional area of the tunnel was measured at its largest diameter within the carpal tunnel. All the dimensions were measured in centimeters. Results The mean transverse diameter of the right side was 1.824 ± 0.223 cm (p-value 0.002) and of the left side was 1.742 ± 0.197 cm (p-value 0.004). The mean cross-sectionalarea of the carpal tunnel on the right side was 1.417 ± 0.379 cm2 (p-value 0.008) and on the left side was 1.306 ± 0.303 cm2(p-value 0.004), respectively. Age, sex, weight, and BMI were discussed. The carpal tunnels of females were found to be comparatively squarer and smaller than those of males. Conclusion The transverse diameter and cross-sectional area of the carpal tunnel and their correlation with carpal tunnel syndromeare predicted by age, sex, weight, and BMI. Both sexes had the same wrist ratio.

Gait analysis: An effective tool to mechanically monitor the bone regeneration of critical-sized defects in tissue engineering applications.

Tissue engineering has emerged as an innovative approach to treat critical-size bone defects using biocompatible scaffolds, thus avoiding complex distraction surgeries or limited stock grafts. Continuous regeneration monitoring is essential in critical-size cases due to the frequent appearance of non-unions. This work evaluates the potential clinical use of gait analysis for the mechanical assessment of a tissue engineering regeneration as an alternative to the traditional and hardly conclusive manual or radiological follow-up. The 15-mm metatarsal fragment of eight female merino sheep was surgically replaced by a bioceramic scaffold stabilized with an external fixator. Gait tests were performed weekly by making the sheep walk on an instrumented gangway. The evolution of different kinematic and dynamic parameters was analyzed for all the animal's limbs, as well as asymmetries between limbs. Finally, potential correlation in the recovery of the gait parameters was evaluated through the linear regression models. After surgery, the operated limb has an altered way of carrying body weight while walking. Its loading capacity was significantly reduced as the stance phases were shorter and less impulsive. The non-operated limbs compensated for this mobility deficit. All parameters were normalizing during the consolidation phase while the bone callus was simultaneously mineralizing. The results also showed high levels of asymmetry between the operated limb and its contralateral, which exceeded 150% when analyzing the impulse after surgery. Gait recovery significantly correlated between symmetrical limbs. Gait analysis was presented as an effective, low-cost tool capable of mechanically predicting the regeneration of critical-size defects treated by tissue engineering, as comparing regeneration processes or novel scaffolds. Despite the progressive normalization as the callus mineralized, the bearing capacity reduction and the asymmetry of the operated limb were more significant than in other orthopedic alternatives.

Symmetrical Peripheral Gangrene resulting from application of henna: a rare clinical occurrence

Symmetrical Peripheral Gangrene (SPG) is a rare clinical syndrome characterized by bilateral symmetric distal limb ischemia leading to gangrene with no evidence of major vascular occlusive disease. The peripheral pulses are usually palpable as a result of the sparing of larger vessels. The mechanism of vascular occlusion is poorly understood. Disseminated intravascular coagulation has been implicated as the final common pathway in its pathogenesis. Initial management is resuscitation followed by amputation when the gangrene becomes demarcated. We report a rare case of symmetrical peripheral gangrene of both hands and feet in a 28-year-old female who presented with pain and darkening of all her fingers and toes for 2 days following the application of henna, with no medical history of the known predisposing conditions. She had amputation of the digits of her hands and tarsometatarsal amputation of her feet bilaterally. She had an uneventful postoperative period and was discharged to see the outpatient department. While reported cases of SPG due to numerous etiologies can be found in the literature, this is to our findings the first time we are seeing it resulting from the cosmetic use of henna. The intriguing case presented here was brought about by the application of henna used as a cosmetic agent and was characterized by a very rapid clinical course with no other apparent predisposing etiology.

Tuberculous Radiculomyelitis Presenting as Bilaterally Symmetrical Proximal Lower Limb Weakness

Tuberculous Radiculomyelitis Presenting as Bilaterally Symmetrical Proximal Lower Limb Weakness

Evidence-Based Application of the Plasma Exchange to Improve Muscle Power and Disability Grade in Patients with Guillain-Barré Syndrome

<p>格林-巴利症候群是罕見且病程進展快速的急性周邊神經系統病變，未及時治療，將導致四肢癱瘓及呼吸衰竭。本文描述一位71歲男性，接種AstraZeneca（AZ）疫苗後，出現對稱性肢體無力及右側顏面麻痺，經檢查確診為AZ疫苗誘發格林-巴利症候群的急性發炎性脫髓鞘多發性神經病變合併右側貝爾氏麻痺。筆者以神經科專科護理師角度，評估病人與家屬對治療方案之選擇呈現意見分歧，故運用實證方法探討血漿置換術對改善肌肉力量與殘疾程度之成效。 於Cochrane、Embase、MEDLINE、PubMed、 CINAHL及華藝等資料庫，使用“Guillain-Barre Syndrome”、“plasma exchange”、“intravenous immunoglobulin”、“muscle power”及“disability grade”之關鍵字，搜尋2013 年1月至2023 年2月之中英文文獻。經篩選後共計納入3篇研究進行分析，使用OCEBM評讀文獻，結果顯示治療第2週後，接受血漿置換術之介入措施對於殘疾等級和肌肉力量之改善高於靜脈注射免疫球蛋白。本實證應用結果，病人於住院期間確實恢復肌肉力量及改善殘疾程度。希冀藉由此案例分享，做為爾後照護之參考。</p> <p> </p><p>Guillain-Barré syndrome is a rare and rapidly progressing disease characterized by acute peripheral neuropathy. If left untreated, it can lead to quadriplegia and respiratory failure. In this case, a 71-year-old male developed symmetric limb weakness and right facial palsy after receiving the AstraZeneca (AZ) vaccine. The case was diagnosed with acute inflammatory demyelinating polyneuropathy, a form of Guillain-Barré syndrome, along with right Bell’s palsy. The author, a neurological nurse practi-tioner, was trying to resolve the differences in treatment preferences between the patient and his fami-ly members. Therefore, an evidence-based approach was employed to explore the effectiveness of plas-ma exchange in improving muscle strength and disability grade. An electronic literature search was conducted in databases including Cochrane, Embase, MEDLINE, PubMed, CINAHL, and Airiti Li-brary. Keywords such as “Guillain-Barré Syndrome,” “Plasma Exchange,” “Intravenous Immunoglob-ulin,” “Muscle Power,” and “Disability Grade” were applied. Studies in Chinese or English published between January 2013 and February 2023 were screened and three relevant studies were included in the analysis. The Oxford Centre for Evidence-Based Medicine criteria were further applied to review the literature. The results showed that plasma exchange intervention resulted in a greater improvement in disability grade and muscle power compared to intravenous immunoglobulin after the second week of treatment. Empirical evidence indicated that the patient indeed regained muscle strength and im-proved their disability grade during hospitalization. This case is shared as a reference for future care considerations.</p> <p> </p>

Dengue-induced Guillain–Barre syndrome: a case series

BackgroundDengue virus is an RNA virus that is associated with a myriad of neurological manifestations. Less than 5% of patients develop neuromuscular complications. Guillain–Barre syndrome (GBS) is an uncommon neurological sequelae of dengue fever. Studies have shown acute motor axonal neuropathy (AMAN) and acute motor sensory axonal neuropathy (AMSAN) to be the most common variants associated with dengue fever in Asian countries. Very few cases have been reported from Pakistan to date.Case presentationWe present four adult patients with dengue-associated GBS. The time interval between onset of symptoms of dengue fever and development of lower limb weakness in all patients was between 6 and 20 days. Dengue was diagnosed based on either serology or dengue NS1 antigen testing. Acute inflammatory demyelinating polyneuropathy (AIDP) (n = 1), AMAN (n = 1), and AMSAN (n = 2) variants were identified. One patient had a coexisting myopathy which has not been previously reported. All patients showed good recovery after treatment with plasmapheresis or intravenous immunoglobulins.ConclusionsOur case series is valuable in contributing to the limited pool of reported cases of dengue fever complicated by GBS. Early detection of new onset symmetrical limb weakness during or after a dengue infection is imperative for early treatment and to limit disability.

Case study of Guillain-Barré syndrome with acute flaccid paralysis

Guillain-Barre syndrome (GBS) is a sudden and a complicated degenerative neurological disorder which can be acute or chronic in nature. Etiology remains unclear, but pathophysiology shows demyelination of spinal nerve roots characterised by symmetrical limb weakness and muscle stiffness. Death is rare. Early diagnosis and prompt treatment should occur in severe cases. Here we discuss a rare case of GBS as paraesthesia and acute flaccid paralysis. This case report focuses on a 9-year-old male patient presenting with c/o progressive muscle weakness and paraesthesia in the lower extremities. The clinical examination revealed bilateral lower limb weakness, absent deep tendon reflexes, and diminished vibration sense, acute flaccid paralysis. Diagnostic evaluations of CT scan of brain and spine and other preliminary tests confirmed the diagnosis of GBS by demonstrating characteristic findings of demyelinating polyneuropathy and elevated protein levels without pleocytosis, respectively. Prompt initiation of intravenous immunoglobulin therapy and supportive measures, such as physical therapy, were implemented. Over a four-week period, the patient showed progressive improvement in muscle strength, starting from the slight movement in fingers and toes. This case report underscores the importance of accurate diagnosis, and timely initiation of appropriate treatment strategies in managing GBS, highlighting the efficacy of intravenous immunoglobulin therapy as a first-line intervention for GBS patients.

Femoral Magnetic Lengthening After Distal Femur Endoprosthetic Reconstruction in a Pediatric Patient: A Case Report.

A 10-year-old boy with osteosarcoma of the left distal femur underwent resection with compressive osseointegration endoprosthetic reconstruction, gradually resulting in a 4.5-cm leg-length difference with significant predicted progression. Two years after resection, he underwent right distal femur and proximal tibia epiphysiodesis and placement of a left femoral magnetic lengthening nail. At 2 years after lengthening and skeletal maturity, the patient has symmetric limb lengths, no pain, and returned to sports. A magnetic lengthening nail with contralateral epiphysiodesis is a viable option for correcting limb-length discrepancy after distal femur endoprosthetic reconstruction in a pediatric patient.

Dynamic Modeling and Performance Evaluation of a 5-DOF Hybrid Robot for Composite Material Machining

Dynamic performance is an important performance of robots used for machine processing. This paper studies the dynamic modeling and evaluation method of a 5-DOF (Degree of Freedom) hybrid robot used in aerospace composite material processing. With the consideration of the dynamics of the serial part, the complete dynamic model of the hybrid robot is established based on the virtual work principle. In addition to the widely considered acceleration term, a dynamic performance evaluation index that comprehensively considers the acceleration term, velocity term and gravity term in the dynamic model is proposed. Using the dynamic performance index, the effect of the placement direction of the robot and the arrangement of the double symmetric limbs on robot dynamics are investigated. The results indicate that the vertical placement is beneficial to the dynamics of the hybrid robot, and the arrangement of double symmetric limbs has different effects on different limbs.

Physeal Sparing Proximal Femoral Endoprosthetic Reconstruction with a Short Distal Segment: A Case Report

Background: A custom endoprosthesis allowed for the preservation of the distal femoral physis with a short remaining metaphyseal segment after osteosarcoma resection in a 10-year-old boy. CASE Case Presentation: This case illustrates a reconstructive alternative allowing physeal sparing with minimal remaining metaphyseal bone. At the three-year follow-up, the patient has remained complication-free with distal femoral growth maintaining symmetric limb length. Conclusion: When intercalary biologic reconstruction is not an option and the sacrifice of physis necessitates an extendible total femoral prosthesis, custom physeal sparing short segment press-fit fixation is an appropriate solution.

VRK1 mutation associated with adult-onset spinal muscular atrophy and persistently elevated creatine kinase (P3-8.011)

<h3>Objective:</h3> NA <h3>Background:</h3> NA <h3>Design/Methods:</h3> We present a patient with persistently elevated creatinine kinase and a clinical syndrome consistent with adult-onset spinal muscular atrophy (dSMA) without pontocerebellar atrophy secondary to a vaccinia-related kinase 1 (VRK1) mutation. <h3>Results:</h3> A 46-year-old male presented for evaluation of persistently elevated creatinine kinase, leg weakness, and decreased balance for more than 5 years. He reported mild weakness mainly in the lower extremities and reduced calf size. The patient has had persistently elevated creatine kinase (CK) for the past 5 years, ranging from 580–7,000 units/L. On examination, he had bilateral high arches, calf fasciculations, and atrophy. Motor showed decreased strength in feet dorsiflexion and minimal bilateral hand interosseous weakness. Reflexes were normal except for the absent left ankle reflex. The rest of the neurologic examination was unremarkable. EMG/NCS showed reduced motor responses with diffuse neurogenic changes in the right arm and leg concerning for motor neuropathy. CK level remained elevated along with aldolase; otherwise negative myopathy labs. The neuropathy panel showed two pathogenic mutations of the VRK1 gene, variant c1072C&gt;T (p.Arg358) and c.356 A&gt;G (p.His119Arg), consistent with compound heterozygosity. <h3>Conclusions:</h3> VRK1 mutation is a rare cause of distal predominant spinal muscular atrophy. This disease is characterized by slowly progressive distal symmetric limb muscle weakness and atrophy, frequently leading to foot deformities such as pes cavus, with minimal or no sensory involvement. Mild elevations in CK can be seen in up to 50% of motor neuron disease cases. Our patient’s presentation was consistent with adult-onset spinal muscular atrophy. There was no pontocerebellar hypoplasia, which has also been described with this mutation. Creatine kinase level remained very elevated in our patient, beyond what has previously been described in the literature. Future investigation should be done to determine the significance of this, including whether there may be a myopathic component to this illness. <b>Disclosure:</b> Dr. Rodriguez-Hernandez has nothing to disclose. Dr. Carranza-Renteria has nothing to disclose. Dr. Faktorovich has a non-compensated relationship as a Board of Directors with Brother’s Brother Foundation that is relevant to AAN interests or activities.

SPINAL MUSCULAR ATROPHY CLINICAL FEATURES, CLASSIFICATION, NATURAL HISTORY, GENETICS, DIAGNOSIS, COMPLICATIONS AND TREATMENT OF THE DISEASE

Introduction: Spinal muscular atrophy (SMA) is a complex neuromuscular disorder, it is the most usual autosomal recessively inherited lethal neuromuscular disease in pediatrics, it presents a defective alteration in the survival motor neuron 1 (SMN1) gene. Spinal muscular atrophy clinically shows progressive weakness of skeletal and respiratory muscles. In recent years, drugs with encouraging results from phase II and III clinical trials have been presented. Objective: to detail current information related to spinal muscular atrophy, clinical features, classification, natural history, genetics, diagnosis, complications and treatment of the disease. Methodology: a total of 40 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 31 bibliographies were used because the other articles were not relevant to this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: spinal muscular atrophy, Spinal Muscular Atrophy, spinal muscular atrophy and spinal muscular atrophy. Results: About 95 % of the occurrences of spinal muscular atrophy are generated by homozygous deletions. Individuals with 5q mutation make up 95% of cases of spinal muscular atrophy and the remaining 5% are generated by mutations in 5q1-5. Targeted treatments may prevent or delay the progression of some symptoms of spinal muscular atrophy. Conclusions: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by muscle atrophy and weakness resulting from irreversible loss and progressive degeneration of the brainstem nuclei and anterior horn cells in the spinal cord (lower motor neurons). Clinically it presents with symmetrical proximal limb weakness that also impacts the axial muscles, intercostal and bulbar musculature and is progressive, and the classification protocol is important in genetics, as well as providing prognostic and clinical information. The natural history of the disease is variable and complicated. It is made by demonstrating a history of proximal muscle weakness, motor difficulties or regression, diminished or absent deep tendon reflexes. Among the most frequent complications in unsupported individuals are those previously mentioned such as poor weight gain with growth retardation, scoliosis, restrictive lung disease, joint contractures and sleep difficulties. In terms of treatment, several different compounds have been investigated in recent years, focused on increasing muscle strength and function. Proactive supportive treatment involving a multidisciplinary team is paramount to decrease the severity of symptoms. KEY WORDS: muscle atrophy, spine, spinal, spinal cord, motor neuron.

Guillain-Barré Syndrome with Incomplete Oculomotor Nerve Palsy after Traumatic Brain Injury: Case Report and Literature Review

Guillain-Barré syndrome (GBS) is a severe peripheral neuroinflammatory demyelinating disease characterized by symmetrical progressive limb weakness, which can be accompanied by cranial nerve and sensory disturbances. There is usually a history of bacterial or viral infection prior to onset. GBS is rarely seen after traumatic brain injury (TBI). We report a case of a 66-year-old male patient who presented with dilated pupils, followed by respiratory failure and symmetrical quadriplegia during a conservative treatment for TBI. He was eventually diagnosed with GBS and was treated with intravenous immunoglobulin, followed by rehabilitation therapy with a good recovery. We summarize previous similar cases and analyze possible causes. It is suggested that the possibility of GBS should be considered when unexplained symptoms occurred in patients with TBI, such as respiratory failure, dilated pupils, and limb weakness.

Pharyngeal-Cervical-Brachial Variant of Guillain Barre Syndrome

Guillain-Barre Syndrome (GBS) usually present as1 symmetrical ascending muscle weakness associated with areflexia and flaccidity with or without sensory symptoms. However,2 in some patients it may present atypically and one of the rare variant is Pharyngeal-cervical-brachial variant, usually presented as muscle weakness extending from cervical area to the upper extremities often affected with proximal muscle groups. A 20-year-old male presented in ER with complaints of weakness over bilateral upper limb, dysphagia and difficulty in speaking followed by quadriparesis and breathing difficulty. Diagnosis of PCB variant was made by CSF and nerve conduction study and all other possible differentials were excluded.The patient improved by administration of iv immunoglobulin and other supportive measures. Physicians should think about PCB variant of GBS, whenever a patient presenting with symmetrical upper limb weakness and bulbar palsy.

Mimicry of Two Disease Guillain-Barre Syndrome and Japanese encephalitis: A Case Report

Guillian-Barre syndrome (GBS) is an acute immune-mediated inflammatory demyelinating polyneuropathy characterized by symmetrical limb weakness and areflexia preceded by an infection while Japanese encephalitis (JE) virus is a neurotropic RNA virus belonging to Flaviviridae family. GBS can have different clinical manifestations which overlaps JE. GBS secondary to JE has been reported earlier though in the incidence is low.Involvement of the peripheral nerve, areflexic paralysis, electrophysiological nerve examination and JE IgM in CSF were consistent with a diagnosis of GBS with JE. Prompt detection and diagnosis can reduce morbidity and mortality.

Symmetrical Posterior Lower Limb Bruising in A Qatar 2022 FIFA World Cup Fan – A Case Report

Suspected spontaneous ecchymoses may indicate rare but serious underlying bleeding disorders. By undertaking a thorough clinical assessment and appropriately safety-netting patients, clinicians can reduce the need for unnecessary investigations and follow-up. Objective: To report a case of symmetrical posterior lower limb bruising in a Qatari male football fan twelve-hours following his attendance at a Qatar 2022 FIFA World Cup match in Doha, Qatar. Background: A 36-year-old previously fit and well Qatari male presented routinely to a primary healthcare centre in Doha, Qatar, after waking with painless bruising to the posterior aspects of both thighs and calves. He attended a Qatar 2022 World Cup football match as a fan the evening before, and reported being completely well prior to this. He scored 0 on both the Bleeding Assessment Score and Wells’ Criteria for DVT. Following a thorough history, examination and laboratory studies to exclude possible bleeding disorders, a diagnosis of simple purpura was made. The patient was reviewed a week later, and confirmed complete resolution. Conclusions: Fit and well football fans presenting with bruising to the dorsum of the legs in a similar pattern can, following a thorough assessment, be diagnosed with simple purpura. Key Words: Bruising, ecchymosis, football fan, soccer fan, Fan Seat Bruising

Behavioral context improves optogenetic stimulation of transplanted dopaminergic cells in unilateral 6-OHDA rats

Stem cell therapy has long been a popular method of treatment for Parkinson’s disease currently being researched in both preclinical and clinical settings. While early clinical results are based upon fetal tissue transplants rather than stem cell transplants, the lack of successful integration in some patients and gradual loss of effect in others suggests a more robust protocol is needed. We propose a two-front approach, one where transplants are directly stimulated in coordination with host activity elicited by behavioral tasks, which we refer to as behavioral context. After a pilot with unilateral 6-OHDA rats transplanted with dopaminergic cells differentiated from mesenchymal stem cells that were optogenetically stimulated during a swim task, we discovered that early stimulation predicted lasting reduction of motor deficits, even in the absence of later stimulation. This led to a follow-up with n = 21 rats split into three groups: one stimulated while performing a swim task (Stim-Swim; St-Sw), one not stimulated while swimming (NoStim-Swim; NSt-Sw), and one stimulated while stationary in a bowl (Stim-NoSwim; St-NSw). After initial stimulation (or lack thereof), all rats were retested two and seven days later with the swim task in the absence of stimulation. The St-Sw group gradually achieved and maintained symmetrical limb use, whereas the NSt-Sw group showed persistent asymmetry and the St-NSw group showed mixed results. This supports the notion that stem cell therapy should integrate targeted stimulation of the transplant with behavioral stimulation of the host tissue to encourage proper functional integration of the graft.