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Frontiers in Immunology 2024Poisoning by widow-spider (genus ) bites occurs worldwide. The illness, termed latrodectism, can cause severe and persistent pain and can lead to muscle rigidity,...
Poisoning by widow-spider (genus ) bites occurs worldwide. The illness, termed latrodectism, can cause severe and persistent pain and can lead to muscle rigidity, respiratory complications, and cardiac problems. It is a global health challenge especially in developing countries. Equine serum-derived polyclonal anti-sera are commercially available as a medication for patients with latrodectism, but the use of sera imposes potential inherent risks related to its animal origin. The treatment may cause allergic reactions in humans (serum sickness), including anaphylactic shock. Furthermore, equine-derived antivenom is observed to have batch-to-batch variability and poor specificity, as it is always an undefined mix of antibodies. Because latrodectism can be extremely painful but is rarely fatal, the use of antivenom is controversial and only a small fraction of patients is treated. In this work, recombinant human antibodies were selected against alpha-latrotoxin of the European black widow () by phage display from a naïve antibody gene library. Alpha-Latrotoxin (α-LTX) binding scFv were recloned and produced as fully human IgG. A novel alamarBlue assay for venom neutralization was developed and used to select neutralizing IgGs. The human antibodies showed neutralization efficacy both as single antibodies and antibody combinations. This was also confirmed by electrophysiological measurements of neuronal activity in cell culture. The best neutralizing antibodies showed nanomolar affinities. Antibody MRU44-4-A1 showed outstanding neutralization efficacy and affinity to α-LTX. Interestingly, only two of the neutralizing antibodies showed cross-neutralization of the venom of the Southern black widow (). This was unexpected, because in the current literature the alpha-latrotoxins are described as highly conserved. The here-engineered antibodies are candidates for future development as potential therapeutics and diagnostic tools, as they for the first time would provide unlimited supply of a chemically completely defined drug of constant quality and efficacy, which is also made without the use of animals.
Topics: Humans; Animals; Black Widow Spider; Antibodies, Neutralizing; Spider Venoms; Antivenins; Single-Chain Antibodies; Spider Bites; Immunoglobulin G
PubMed: 38933276
DOI: 10.3389/fimmu.2024.1407398 -
Medicina (Kaunas, Lithuania) Jun 2024Patients with movement disorders such as Parkinson's disease (PD) living in remote and underserved areas often have limited access to specialized healthcare, while the... (Review)
Review
Patients with movement disorders such as Parkinson's disease (PD) living in remote and underserved areas often have limited access to specialized healthcare, while the feasibility and reliability of the video-based examination remains unclear. The aim of this narrative review is to examine which parts of remote neurological assessment are feasible and reliable in movement disorders. Clinical studies have demonstrated that most parts of the video-based neurological examination are feasible, even in the absence of a third party, including stance and gait-if an assistive device is not required-bradykinesia, tremor, dystonia, some ocular mobility parts, coordination, and gross muscle power and sensation assessment. Technical issues (video quality, internet connection, camera placement) might affect bradykinesia and tremor evaluation, especially in mild cases, possibly due to their rhythmic nature. Rigidity, postural instability and deep tendon reflexes cannot be remotely performed unless a trained healthcare professional is present. A modified version of incomplete Unified Parkinson's Disease Rating Scale (UPDRS)-III and a related equation lacking rigidity and pull testing items can reliably predict total UPDRS-III. UPDRS-II, -IV, Timed "Up and Go", and non-motor and quality of life scales can be administered remotely, while the remote Movement Disorder Society (MDS)-UPDRS-III requires further investigation. In conclusion, most parts of neurological examination can be performed virtually in PD, except for rigidity and postural instability, while technical issues might affect the assessment of mild bradykinesia and tremor. The combined use of wearable devices may at least partially compensate for these challenges in the future.
Topics: Humans; Telemedicine; Movement Disorders; Neurologic Examination; Parkinson Disease; Tremor
PubMed: 38929575
DOI: 10.3390/medicina60060958 -
PloS One 2024Minimalist shoes (MS) are beneficial for foot health. The foot is a part of the posterior chain. It is suggested that interventions on the plantar foot sole also affect... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Minimalist shoes (MS) are beneficial for foot health. The foot is a part of the posterior chain. It is suggested that interventions on the plantar foot sole also affect the upper segments of the body. This study aimed to investigate the local and remote effects along the posterior chain of four weeks of MS walking in recreationally active young adults.
METHODS
28 healthy participants (15 female, 13 male; 25.3 ± 5.3 years; 70.2 ± 11.9 kg; 175.0 ± 7.8 cm) were randomly assigned to a control- or intervention group. The intervention group undertook a four-week incremental MS walking program, which included 3,000 steps/day in the first week, increasing to 5,000 steps/day for the remaining three weeks. The control group walked in their preferred shoe (no MS). We assessed the following parameters in a laboratory at baseline [M1], after the four-week intervention [M2], and after a four-week wash-out period [M3]: Foot parameters (i.e., Foot Posture Index-6, Arch Rigidity Index), static single-leg stance balance, foot-, ankle-, and posterior chain range of motion, and muscle strength of the posterior chain. We fitted multiple hierarchically built mixed models to the data.
RESULTS
In the MS group, the Foot Posture Index (b = -3.72, t(51) = -6.05, p < .001, [-4.94, 2.51]) and balance (b = -17.96, t(49) = -2.56, p = .01, [-31.54, 4.37]) significantly improved from M1 to M2, but not all other parameters (all p >.05). The improvements remained at M3 (Foot Posture Index: b = -1.71, t(51) = -2.73, p = .009, [-4,94,0.48]; balance: b = -15.97, t(49) = -2.25, p = .03, [-29.72, 2.21]).
DISCUSSION
Walking in MS for four weeks might be advantageous for foot health of recreationally active young adults but no chronic remote effects should be expected.
Topics: Humans; Female; Male; Walking; Foot; Adult; Postural Balance; Shoes; Young Adult; Posture; Range of Motion, Articular; Muscle Strength
PubMed: 38900749
DOI: 10.1371/journal.pone.0304640 -
Journal of the Neurological Sciences Jun 2024Sex differences affect Parkinson's disease (PD) development and manifestation. Yet, current PD identification and treatments underuse these distinctions. Sex-focused PD...
Sex differences affect Parkinson's disease (PD) development and manifestation. Yet, current PD identification and treatments underuse these distinctions. Sex-focused PD literature often prioritizes prevalence rates over feature importance analysis. However, underlying aspects could make a feature significant for predicting PD, despite its score. Interactions between features require consideration, as do distinctions between scoring disparities and actual feature importance. For instance, a higher score in males for a certain feature doesn't necessarily mean it's less important for characterizing PD in females. This article proposes an explainable Machine Learning (ML) model to elucidate these underlying factors, emphasizing the importance of features. This insight could be critical for personalized medicine, suggesting the need to tailor data collection and analysis for males and females. The model identifies sex-specific differences in PD, aiding in predicting outcomes as "Healthy" or "Pathological". It adopts a system-level approach, integrating heterogeneous data - clinical, imaging, genetics, and demographics - to study new biomarkers for diagnosis. The explainable ML approach aids non-ML experts in understanding model decisions, fostering trust and facilitating interpretation of complex ML outcomes, thus enhancing usability and translational research. The ML model identifies muscle rigidity, autonomic and cognitive assessments, and family history as key contributors to PD diagnosis, with sex differences noted. The genetic variant SNCA-rs356181 may be more significant in characterizing PD in males. Interaction analysis reveals a greater occurrence of feature interplay among males compared to females. These disparities offer insights into PD pathophysiology and could guide the development of sex-specific diagnostic and therapeutic approaches.
PubMed: 38870732
DOI: 10.1016/j.jns.2024.123091 -
BMC Psychiatry Jun 2024Malignant hyperthermia is a potentially lethal condition triggered by specific anesthetic drugs, especially a depolarizing muscle relaxant of succinylcholine...
BACKGROUND
Malignant hyperthermia is a potentially lethal condition triggered by specific anesthetic drugs, especially a depolarizing muscle relaxant of succinylcholine (Suxamethonium). Despite the frequent use of succinylcholine with electroconvulsive therapy (ECT), there has been no reported case of potentially lethal malignant hyperthermia following ECT. In addition, the time interval between the administration of succinylcholine and the onset of malignant hyperthermia has not been outlined in the context of ECT.
CASE PRESENTATION
We present the case of a 79-year-old woman suffering from severe depression, who experienced severe malignant hyperthermia due to succinylcholine administration during an ECT session. She presented with a high fever of 40.2 °C, tachycardia of 140/min, hypertension with a blood pressure exceeding 200 mmHg, significant muscle rigidity, and impaired consciousness. These symptoms emerged two hours after ECT, which occurred in a psychiatric ward rather than an operating room, and reached their peak in less than 24 h. She was given 60 mg of dantrolene, which quickly reduced the muscular rigidity. Subsequently, she received two additional doses of 20 mg and 60 mg of dantrolene, which brought her fever down to 36.2 °C and completely eased her muscle rigidity within two days after ECT.
CONCLUSIONS
This is the first reported case of potentially lethal malignant hyperthermia after ECT. In addition, it highlights the delayed onset of malignant hyperthermia following an ECT procedure, emphasizing the necessity for psychiatrists to recognize its onset even after the treatment. In the light of potentially lethal consequences of malignant hyperthermia, it is critically important for psychiatrists to closely monitor both intraoperative and postoperative patient's vital signs and characteristic physical presentations, promptly identify any symptomatic emergence, and treat it immediately with dantrolene.
Topics: Humans; Succinylcholine; Electroconvulsive Therapy; Aged; Malignant Hyperthermia; Female; Neuromuscular Depolarizing Agents; Dantrolene; Psychiatrists
PubMed: 38834964
DOI: 10.1186/s12888-024-05846-5 -
Neuropsychopharmacology Reports Jun 2024Neuroleptic malignant syndrome (NMS) is a rare and potentially life-threatening condition that may arise at any point during treatment and is often associated with...
BACKGROUND
Neuroleptic malignant syndrome (NMS) is a rare and potentially life-threatening condition that may arise at any point during treatment and is often associated with adverse reactions to dopamine-blocking agents. This syndrome is normally characterized by features such as muscle rigidity, alteration in consciousness, autonomic instability, and leukocytosis.
AIM
The aim of this study is to investigate a borderline intellectual functioning (BIF) case in which NMS with insidious disease progression and long prodromal symptoms was developed.
CASE PRESENTATION
The investigated patient was a 38-year-old female diagnosed with bipolar disorder and a variety of corresponding disorders. The patient exhibited gastrointestinal symptoms and restlessness in the weeks leading up to the study, subsequent to the administration of elevated doses of haloperidol, risperidone, and lithium. In addition, she was hospitalized for restlessness and aggressiveness in the summer of 2023. Furthermore, due to her chief complaint, she received parenteral haloperidol twice in the emergency room, subsequently experiencing fever, altered consciousness, generalized rigidity, and dysphagia. Moreover, the patient's initial creatine phosphokinase (CPK) level was 2550 IU/L, and she was hospitalized in an intensive care unit with the diagnosis of NMS for 8 days.
CONCLUSIONS
This case study highlights the necessity of being attentive about prodromal symptoms of NMS and emergent interventions.
PubMed: 38832410
DOI: 10.1002/npr2.12454 -
Nature Communications May 2024Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson's disease. Potentially, improving each symptom may...
Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson's disease. Potentially, improving each symptom may require stimulation of different white matter tracts. Here, we study a large cohort of patients (N = 237 from five centers) to identify tracts associated with improvements in each of the four symptom domains. Tremor improvements were associated with stimulation of tracts connected to primary motor cortex and cerebellum. In contrast, axial symptoms are associated with stimulation of tracts connected to the supplementary motor cortex and brainstem. Bradykinesia and rigidity improvements are associated with the stimulation of tracts connected to the supplementary motor and premotor cortices, respectively. We introduce an algorithm that uses these symptom-response tracts to suggest optimal stimulation parameters for DBS based on individual patient's symptom profiles. Application of the algorithm illustrates that our symptom-tract library may bear potential in personalizing stimulation treatment based on the symptoms that are most burdensome in an individual patient.
Topics: Humans; Deep Brain Stimulation; Parkinson Disease; Male; Female; Middle Aged; Aged; Tremor; Motor Cortex; Algorithms; Hypokinesia; White Matter; Muscle Rigidity; Cerebellum; Cohort Studies; Treatment Outcome
PubMed: 38821913
DOI: 10.1038/s41467-024-48731-1 -
Cureus Apr 2024Stiff Person Syndrome (SPS) is a rare autoimmune condition marked by extremely painful muscle spasms, stiffness, and rigidity throughout the body. Its rarity often...
Stiff Person Syndrome (SPS) is a rare autoimmune condition marked by extremely painful muscle spasms, stiffness, and rigidity throughout the body. Its rarity often translates to limited treatment options for patients and, occasionally, challenges in obtaining a definitive diagnosis. SPS also impacts patients' mental health, social and economic involvement, and overall quality of life. A 43-year-old man was initially being seen for lumbar radicular pain. A clinical diagnosis of SPS was made by a neurologist and confirmed by in-clinic follow-ups and anti-glutamic acid decarboxylase (anti-GAD) antibody testing. The Pain Management doctor agreed with this diagnosis and offered intravenous (IV) ketamine treatment, which he has found to positively impact the treatment of similar disorders. After an initial 10-day infusion, the patient reported improvement in pain and function. For almost two years, the patient received intravenous immunoglobulin (IVIg) and IV ketamine treatments to manage their condition and maintain pain control as well as quality of life. When the patient's symptoms began worsening after IVIg infusions, the decision to withdraw IVIg infusions and continue ketamine infusions was made. After discontinuing IVIg infusions, the patient reported improvement in function and pain level and continues to receive monthly two-day ketamine boosters. Outside of the infusions, the patient was able to discontinue the use of fentanyl patches and continued taking ketamine lozenges, oxycodone-acetaminophen, and dextromethorphan for at-home pain management. The patient's symptoms continue to be managed effectively with their current regimen, enabling their return to work and experiencing an enhanced quality of life. This case illustrates the potential benefits of IV ketamine treatment for patients with treatment-resistant SPS and similar neurologic and autoimmune disorders. Understanding and examining treatment alternatives for rare syndromes is crucial for achieving optimal patient outcomes. Additionally, documenting such cases offers valuable insights into the mechanism of ketamine, extending beyond these syndromes.
PubMed: 38817534
DOI: 10.7759/cureus.59397 -
Therapeutic Hypothermia and Temperature... Jun 2024Malignant hyperthermia (MH) is a rare, life-threatening condition caused by alterations in skeletal muscle calcium channels inherited through an autosomal dominant...
Malignant hyperthermia (MH) is a rare, life-threatening condition caused by alterations in skeletal muscle calcium channels inherited through an autosomal dominant pattern. The use of specific agents in anesthesia such as inhaled anesthetics and succinylcholine can precipitate a hyperthermic crisis. Patients experience a rapid increase in muscle rigidity, secondary to skeletal muscle calcium dysregulation, leading to acute rhabdomyolysis and possible hyperthermia. Providers must have a high index of suspicion of this disease process because early diagnosis is critical to mortality reduction. Management centers around removal of the offending agent, dantrolene, and supportive care including cooling if hyperthermic. Intravascular cooling devices have been used in thermodynamic regulation after cardiac arrest and have shown to be more effective than dermal cooling techniques; however, they have not been well described in other disease processes. The following case report is the first to describe a patient suffering from MH to undergo invasive intravenous cooling in order to counteract the effects of this life-threatening disease.
Topics: Humans; Malignant Hyperthermia; Hypothermia, Induced; Male; Treatment Outcome
PubMed: 38808487
DOI: 10.1089/ther.2024.0004 -
Medicina (Kaunas, Lithuania) Apr 2024This study delves into the multifaceted approaches to treating Parkinson's disease (PD), a neurodegenerative disorder primarily affecting motor function but also... (Review)
Review
This study delves into the multifaceted approaches to treating Parkinson's disease (PD), a neurodegenerative disorder primarily affecting motor function but also manifesting in a variety of symptoms that vary greatly among individuals. The complexity of PD symptoms necessitates a comprehensive treatment strategy that integrates surgical interventions, pharmacotherapy, and physical therapy to tailor to the unique needs of each patient. Surgical options, such as deep brain stimulation (DBS), have been pivotal for patients not responding adequately to medication, offering significant symptom relief. Pharmacotherapy remains a cornerstone of PD management, utilizing drugs like levodopa, dopamine agonists, and others to manage symptoms and, in some cases, slow down disease progression. However, these treatments often lead to complications over time, such as motor fluctuations and dyskinesias, highlighting the need for precise dosage adjustments and sometimes combination therapies to optimize patient outcomes. Physical therapy plays a critical role in addressing the motor symptoms of PD, including bradykinesia, muscle rigidity, tremors, postural instability, and akinesia. PT techniques are tailored to improve mobility, balance, strength, and overall quality of life. Strategies such as gait and balance training, strengthening exercises, stretching, and functional training are employed to mitigate symptoms and enhance functional independence. Specialized approaches like proprioceptive neuromuscular facilitation (PNF), the Bobath concept, and the use of assistive devices are also integral to the rehabilitation process, aimed at improving patients' ability to perform daily activities and reducing the risk of falls. Innovations in technology have introduced robotic-assisted gait training (RAGT) and other assistive devices, offering new possibilities for patient care. These tools provide targeted support and feedback, allowing for more intensive and personalized rehabilitation sessions. Despite these advancements, high costs and accessibility issues remain challenges that need addressing. The inclusion of exercise and activity beyond structured PT sessions is encouraged, with evidence suggesting that regular physical activity can have neuroprotective effects, potentially slowing disease progression. Activities such as treadmill walking, cycling, and aquatic exercises not only improve physical symptoms but also contribute to emotional well-being and social interactions. In conclusion, treating PD requires a holistic approach that combines medical, surgical, and therapeutic strategies. While there is no cure, the goal is to maximize patients' functional abilities and quality of life through personalized treatment plans. This integrated approach, along with ongoing research and development of new therapies, offers hope for improving the management of PD and the lives of those affected by this challenging disease.
Topics: Humans; Parkinson Disease; Physical Therapy Modalities; Independent Living; Gait; Deep Brain Stimulation; Quality of Life; Exercise Therapy
PubMed: 38792894
DOI: 10.3390/medicina60050711