Spinal cord stimulation for the symptomatic treatment of rigidity and painful spasm in a case of stiff person syndrome.

BACKGROUND: Stiff person syndrome (SPS) is a rare neuroimmunological disorder characterized by rigidity and painful spasm primarily affecting the truncal and paraspinal musculature due to autoimmune-mediated neuronal hyperexcitability. Spinal cord stimulation (SCS) is an approved therapy for managing painful neuropathic conditions, including diabetic peripheral neuropathy and refractory angina pectoris. We describe the novel use of SCS for the treatment of spasm and rigidity in a 49-year-old man with seropositive stiff person syndrome (SPS). The patient was treated with intravenous immunoglobulin (IVIG) and oral medications over a 13-month period with minimal improvement, prompting consideration of SCS. To our knowledge, this is the first report of the successful use of SCS in SPS with the demonstration of multifaceted clinical improvement. METHODS: Following a successful temporary SCS trial, permanent implantation was performed. Spasm/stiffness (Distribution of Stiffness Index; Heightened Sensitivity Scale; Penn Spasm Frequency Scale, PSFS), disability (Oswestry Disability Index, ODI; Pain Disability Index, PDI), depression (Patient Health Questionnaire-9, PHQ-9), sleep (Pittsburgh Sleep Quality Index, PSQI), fatigue (Fatigue Severity Scale, FSS), pain (Numerical Pain Rating Scale, NPRS), quality of life (EuroQoL 5 Dimension 5 Level, EQ-5D-5L), and medication usage were assessed at baseline, 6-month, and 10-month postimplantation. RESULTS: ODI, PHQ-9, FSS, NPRS, PSQI, and EQ-5D-5L scores showed a notable change from baseline and surpassed the defined minimal clinically important difference (MCID) at 6-month and 10-month follow-up. Oral medication dosages were reduced. CONCLUSIONS: The novel use of SCS therapy in seropositive SPS resulted in functional improvement and attenuation of symptoms. We present possible mechanisms by which SCS may produce clinical response in patients with SPS and aim to demonstrate proof-of-concept for a future comprehensive pilot study evaluating SCS-mediated response in SPS.

A Review of Peripheral Nerve Stimulation Techniques Targeting the Medial Branches of the Lumbar Dorsal Rami in the Treatment of Chronic Low Back Pain.

OBJECTIVES: The lumbar medial branch nerve has historically been a focus for ablative techniques in the treatment of chronic low back pain (CLBP) of facetogenic origin. Recent developments in the field of neuromodulation have been employed to target these nerves for analgesia and/or functional restoration in broader populations of CLBP patients. The objective of this article was to provide an introductory review of procedural techniques and devices employed for peripheral nerve stimulation (PNS) of the lumbar medial branch of the dorsal ramus for the treatment of CLBP. METHODS: A literature search via PubMed.gov was performed through September 2019 with key words focusing on peripheral nerve stimulation for chronic low back pain. This was refined to include only those articles that focused specifically on stimulation of the lumbar medial branch of the dorsal ramus. References within selected articles and unpublished data currently in the peer review process were also utilized. RESULTS: Ninety articles from PubMed.gov were obtained. Two approaches to PNS of the medial branch of the dorsal ramus were identified. CONCLUSIONS: Our review of the current literature regarding techniques for neuromodulation of the medial branch of the dorsal ramus revealed two dominant methods: a temporarily implanted percutaneous coiled-lead approach and a permanently implanted system. The two techniques share some similarities, such as targeting the medial branch of the dorsal ramus, and also have some differences, such as indwelling time, stimulation parameters, duration of treatment, image guidance, and degrees of invasiveness, but they are both demonstrating promising results in clinical trials.

Altered Thermoregulatory Responses Following Spinal Morphine for Caesarean Delivery: a Case Report.

OBJECTIVE: Spinal anaesthesia interferes with physiological thermoregulatory responses, potentially leading to peri-operative hypothermia. Spinal morphine can further compound this by a paradoxical clinical presentation leading to poor patient outcome. CASE REPORT: Following an uneventful caesarean delivery (CD) under spinal anaesthesia with intrathecal morphine for post-operative analgesia, a parturient presented in the recovery room with increasing somnolence, excessive sweating and a sensation of feeling hot. She was haemodynamically stable, but her temperature was 34.5°C. Active warming measures were implemented, and normothermia was achieved in 3 hours. CONCLUSION: Spinal morphine can alter the clinical presentation of hypothermia by manifesting as excessive sweating and subjective sensation of warmth. Teams involved in the perioperative care of parturients should be aware of (a) the possibility of spinal anaesthesia causing perioperative hypothermia, (b) intrathecal morphine masking the clinical presentation of hypothermia and (c) the importance of monitoring temperature of patients who have received spinal anaesthesia with added morphine.

Optimal treatment for lumbar spinal stenosis: an update.

PURPOSE OF REVIEW: Our review of current literature within the past 12-24 months for the treatment of lumbar spinals stenosis (LSS) serves to update providers on recent advances and comparisons regarding therapy spanning lifestyle modification, pharmacologic therapy, minimally invasive interventions, and surgical interventions. RECENT FINDINGS: Current literature supporting the inclusion of physical therapy and gabapentin/pregabalin within an initial treatment regimen have been positive. A recent randomized, double-blinded clinical trial of adding calcitonin to epidural steroid injections have shown improvement in pain and function up to 1 year. The minimally invasive lumbar decompression (mild) procedure is showing ongoing beneficial results in pain and function. Spinal cord stimulation (SCS) may have a role for select patients with lumbar spinal stenosis. Finally, the benefits of surgical treatment versus nonsurgical treatment is ultimately inconclusive because of the nature of data collection, inconsistencies with the clinical definition of LSS, and a lack of standardized treatment guidelines. SUMMARY: Our review of current research demonstrates there is a positive role for the current conservative therapies, with favorable results for interventions such as minimally invasive decompression and SCS. Pharmacologic interventions such as systemic prostaglandin analogues and epidural agents such as calcitonin demonstrate early promise, but need to undergo additional safety testing and confirmatory trials. Further long-term research with validated, objective measurements for the aforementioned treatments are needed to draw any definitive conclusions for clinical practice.

Spectrophotometric detection of susceptibility to anti-malarial drugs.

BACKGROUND: With malaria drug resistance increasing in prevalence and severity, new technologies are needed to aid and improve the accuracy and clinical relevance of laboratory or field testing for malaria drug resistance. This study presents a method based on simple and reagentless spectroscopic measurements coupled with comprehensive spectral interpretation analysis that provides valuable quantitative information on the morphological and compositional responses of Plasmodium falciparum and infected red blood cells (IRBCs) to anti-malarial treatment. METHODS: The changes in the size, internal structure, nucleotide and haemozoin composition of the parasites as well as the morphology (size and shape) and haemoglobin composition of the IRBCs treated with dihydroartemisinin (DHA) and mefloquine (MFQ) were investigated using a spectral interpretation analysis. RESULTS: DHA treatment reduced the sizes of the parasites and their structural organelles. The haemoglobin composition of the host IRBCs determined from spectroscopic analysis changed negligibly following DHA treatment. MFQ treated parasites grew to the same size as those from parallel non-treated cultures but lacked haemozoin. Lesser deformation of the cell shape and no haemoglobin depletion were detected for the IRBCs of MFQ treated cultures. CONCLUSIONS: The spectroscopic analysis method proved to be sensitive for recognition of the effects of anti-malarial treatment on the structure and composition of the parasites and IRBCs. The method can have significant potential for research and clinical applications such as evaluating patient specimens for drug action, drug effects or for therapeutic monitoring.

Phenotypic and genotypic analysis of in vitro-selected artemisinin-resistant progeny of Plasmodium falciparum.

Emergence of artemisinin resistance in Cambodia highlights the importance of characterizing resistance to this class of drugs. Previously, intermediate levels of resistance in Plasmodium falciparum were generated in vitro for artelinic acid (AL) and artemisinin (QHS). Here we expanded on earlier selection efforts to produce levels of clinically relevant concentrations, and the resulting lines were characterized genotypically and phenotypically. Recrudescence assays determined the ability of resistant and parent lines to recover following exposure to clinically relevant levels of drugs. Interestingly, the parent clone (D6) tolerated up to 1,500 ng/ml QHS, but the resistant parasite, D6.QHS340×3, recovered following exposure to 2,400 ng/ml QHS. Resistant D6, W2, and TM91c235 parasites all exhibited elevated 50% inhibitory concentrations (IC(50)s) to multiple artemisinin drugs, with >3-fold resistance to QHS and AL; however, the degree of resistance obtained with standard methods was remarkably less than expected for parasite lines that recovered from 2,400-ng/ml drug pressure. A novel assay format with radiolabeled hypoxanthine demonstrated a greater degree of resistance in vitro than the standard SYBR green method. Analysis of merozoite number in resistant parasites found D6 and TM91c235 resistant progeny had significantly fewer merozoites than parent strains, whereas W2 resistant progeny had significantly more. Amplification of pfmdr1 increased proportionately to the increased drug levels tolerated by W2 and TM91c235, but not in resistant D6. In summary, we define the artemisinin resistance phenotype as a decrease in susceptibility to artemisinins along with the ability to recover from drug-induced dormancy following supraclinical concentrations of the drug.

Quantitative analysis of morphological alterations in Plasmodium falciparum infected red blood cells through theoretical interpretation of spectral measurements.

Spectroscopic analysis can provide valuable insights into morphological and biochemical cellular transformations caused by diseases. However, traditional spectroscopic methods and the corresponding spectral interpretation approaches have been challenged by the complexities of the cell shape, orientation, and internal structure. Here we present an elegant spectral interpretation model that enables accurate quantitative analysis of the UV-visible spectra of red blood cells (RBCs) parasitized by the lethal human malaria parasite, Plasmodium falciparum. The model is based on the modified Mie theory (MMT) approach that incorporates the effects of the nonsphericity and orientation and multilayered cell structure to account for complex composition of the infected RBCs (IRBCs). We determine the structure and composition of the IRBCs and address unresolved matters over the alterations induced by the intraerythrocytic development of P. falciparum. The results indicate deformation and swelling of the IRBCs during the trophozoite stage of P. falciparum that is followed by substantial shrinkage during the schizont stages. We determine that up to 90% depletion of hemoglobin from the RBC cytosol does not lead to a net loss of iron from the infected cells. We quantitatively follow the morphological changes in the parasites during the intraerythrocytic development by applying the interpretation model to the UV-visible spectroscopic measurements of the IRBCs. We expect this method of quantitative spectroscopic characterization of the diseased cells to have practical clinical utility for rapid diagnosis, therapeutic monitoring, and drug susceptibility testing.

Interpretation of the ultraviolet-visible spectra of malaria parasite Plasmodium falciparum.

The absorption and scattering properties of three developmental stages of protozoan parasite Plasmodium falciparum were studied both experimentally and theoretically. Experimentally, the light attenuation and forward scattering from parasites extracted from host erythrocyte cultures were measured with UV-visible spectroscopy. The measured spectra were interpreted theoretically with a model based on the core-shell Mie theory in terms of the structural and compositional characteristics of the protozoa. The model accurately reproduced the features of the measured spectra of all developmental stages. The results show that realistic quantitative estimates of the parasite size, nucleotide, and hemozoin contents can be derived from the UV-visible spectroscopy measurements.