Systematic Review of the Clinical Characteristics and Management of Isaac Syndrome.

OBJECTIVES: Isaac syndrome (IS) is a condition characterized by peripheral nerve hyperexcitability caused by voltage-gated potassium channel (VGKC)-complex antibodies. Muscle twitching, stiffness, hypertrophy, and dysautonomic characteristics, such as hyperhidrosis, are common manifestations. The syndrome can be autoimmune or paraneoplastic, with thymoma being a common cause of paraneoplastic IS. Furthermore, this condition could be handed down from one generation to another. However, there is limited information regarding outcomes, relapses, associated syndromes, associated malignancies (other than thymoma), and treatment options. Despite its rarity, there remains a need for effective management strategies for patients with IS. To address this gap, we conducted a systematic review to summarize the most common and effective treatments of IS in immunomodulatory agents and symptomatic medications, as well as to describe outcomes, relapses, and associated malignancies. Altogether, this review serves to guide clinical practice recommendations for IS and highlight areas for further research. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol to conduct a systematic review of cases reposted through the PubMed and Google Scholar databases. The terms "Isaac Syndrome" and "Acquired Neuromyotonia" were used. The Joanna Briggs Institute's critical appraisal tool was used to evaluate the quality of the included studies. RESULTS: We identified 61 case reports and 4 case series, comprising a total of 70 patients with IS (mean age at onset: 42.5 ± 18 years, and 69% were males). Fourteen cases reported relapses. Thymoma was the most common malignancy associated with IS, followed by lymphoma. Among various serum antibodies, voltage-gated potassium channel-complex antibodies were the most reported antibodies elevated in IS (reported in 38 patients and elevated in 21 patients [55.2%]), followed by acetylcholine ganglionic receptor antibodies, which were reported in 30% of patients (n = 21) and were elevated in 5 cases. The most common electromyography findings were myokymic discharges (n = 22), followed by fasciculations (n = 21) and neuromyotonia (n = 19). For treatment, combining anticonvulsants such as carbamazepine with immunotherapy therapy showed the best results in controlling the symptoms. Among immunotherapy therapies, the combination of plasma exchange plus intravenous high-dose steroids achieved the best results in the acute treatment of IS ([n = 6], with improvement noted in 83.3% [n = 5] of cases). Among the symptomatic treatments with anticonvulsants, carbamazepine was the most efficacious anticonvulsant in treatment of IS, with an average effective dosing of 480 mg/day (carbamazepine was used in 32.3% of acute treatment strategies [n = 23], with improvement noted in 73.9% [n = 17] of cases). CONCLUSIONS: IS a rare neuromuscular syndrome that tends to affect middle-aged men. These patients should be screened for thymoma and other malignancies such as lymphomas. The management of IS symptoms can be challenging, but based on our review, the combination of multiple immunosuppressives such as IV steroids and plasmapheresis with anticonvulsants such as carbamazepine seems to achieve the best results.

Resistance profile of genetically distinct clinical Pseudomonas aeruginosa isolates from public hospitals in central Pakistan.

INTRODUCTION: Pseudomonas aeruginosa (member of ESKAPE group) is predominantly responsible for emerging nosocomial infections and poses serious health concern due to ever-increasing drug resistance trends. The current study investigates the prevalence of such highly resistant P. aeruginosa in major hospital settings and further characterizes and compares them for genetic heterogeneity. MATERIALS AND METHODS: Samples of patients (n=108) with wound infections, bacteremia and burn injuries from major hospitals of Rawalpindi and Islamabad during 2017 to 2018 were collected for the present study. The samples were processed in the COMSATS Microbiology and Public Health lab and screened for the P. aeruginosa by routinely used biochemical tests, drug susceptibility tests and rapid molecular approaches. RESULTS: The results suggested that most of the isolates (88/108) are indeed P. aeruginosa (81.4%) underpinning the need of its active surveillance in hospital settings. Further analysis suggested that 32 of these 88 microbes are multi-drug resistance (36.3%), 16 (18.1%) are extensively drug resistance and 4 (4.5%) are pan-drug resistance. Moreover, double disc synergistic test suggested that 16 (18.1%) are positive for metallo-ß-lactamase production. Molecular screening confirmed that 2 (12.5%) and 3 (18.75%) of these 16 isolates are positive for VIM and NDM gene respectively while all the studied isolates were positive for AmpC ß-lactamase. PAP17 isolate harbors both VIM and NDM genes. ERIC PCR profiling showed that majority of MDR bacteria fall in cluster II and III similarly XDR bacteria also fall in cluster II and III while PDR bacteria fall in cluster IV. CONCLUSION: This study revealed that majority of the isolates are multi drug resistant MDR and extensively drug resistant (XDR). However, the presence of some pan drug resistant (PDR) isolates among such small sample size screened is of utmost concern. Molecular typing of extremely resistant P. aeruginosa revealed high genetic diversity. Therefore, we suggest that regular monitoring and surveillance of such highly resistant P. aeruginosa in hospital settings will help to control their transmission and hence reduce the disease burden.