Timectomía transesternal extendida en pacientes con miastenia grave / Extended Transsternal Thymectomy in Patients with Myasthenia Gravis

Introducción: La miastenia grave adquirida es un trastorno de la transmisión neuromuscular, causado por la unión de autoanticuerpos con los componentes de la placa neuromuscular, más frecuentemente con el receptor de acetilcolina. Objetivo: Evaluar los resultados quirúrgicos inmediatos, obtenidos con la timectomía extendida en pacientes con miastenia grave timomatosa y no timomatosa. Métodos: Se realizó un estudio observacional, prospectivo y descriptivo para evaluar los resultados postoperatorios inmediatos de 21 pacientes intervenidos por miastenia grave entre junio de 2015 y mayo de 2020. Las variables estudiadas fueron edad, sexo, lesiones tímicas asociadas y resultados inmediatos: complicaciones y mortalidad ocurridas hasta 30 días de la intervención. Los datos fueron obtenidos de una base en Microsoft Access. Resultados: Dieciséis (76,2 por ciento) pertenecían al sexo femenino y 5 (23, 8 por ciento) al masculino. El mayor número correspondió a la MG con timoma, seguido por la MG e hiperplasia tímica (8) y uno con MG y restos tímicos. Se complicaron tres pacientes (14,3 por ciento). Uno presentó dos complicaciones: enfisema subcutáneo y septicemia, el siguiente, fiebre sin causa aparente y, el último, infección superficial de la herida. No hubo fallecidos. Conclusiones: La timectomía transesternal extendida permite extirpar el timo y la mayor parte de los tejidos adiposo y tímico aberrante, en el cuello y el mediastino. En pacientes tratados por equipos multidisciplinarios, con experiencia en esta cirugía, las complicaciones y la mortalidad tempranas usualmente son favorables(AU)

Introduction: Acquired myasthenia gravis (MG) is a neuromuscular transmission disorder caused by the union of autoantibodies and the components of the neuromuscular plaque, most frequently with the acetylcholine receptor. Objective: To assess the immediate surgical outcomes of extended thymectomy in patients with thymomatous and nonthymomatous myasthenia gravis. Methods: An observational, prospective and descriptive study was carried out to assess the immediate postoperative outcomes of 21 patients operated on for myasthenia gravis between June 2015 and May 2020. The variables studied were age, sex, associated thymic lesions, and immediate outcomes: complications and mortality that occurred up to thirty days after the intervention. The data were obtained from a Microsoft Access database. Results: Sixteen (76.2 percent) belonged to the female sex and five (23.8 percent) to the male sex. The highest number corresponded to MG with thymoma, followed by MG and thymic hyperplasia (8) and one with MG and thymic remains. Three patients (14.3 percent) were complicated. One had two complications: subcutaneous emphysema and septicemia; the next had unexplained fever; and the last one had superficial wound infection. There were no deaths. Conclusions: Extended transsternal thymectomy allows removal of the thymus and most of the adipose and aberrant thymic tissues in the neck and mediastinum. In patients treated by multidisciplinary teams, with experience in this surgery, outcomes regarding early complications and mortality are usually favorable(AU)

B Cell Immunophenotyping and Transcriptional Profiles of Memory B Cells in Patients with Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorders mediated by various autoantibodies. Although most patients with MG require chronic immunosuppressive treatment to control disease activity, appropriate surveillance biomarkers that monitor disease activity or potential toxicity of immunosuppressants are yet to be developed. Herein, we investigated quantitative distribution of peripheral blood B cell subsets and transcriptional profiles of memory B cells (CD19+ CD27+) in several subgroups of MG patients classified according to the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification. This study suggests potential immunologic B-cell markers that may guide treatment decision in future clinical settings.

Miastenia gravis seronegativa: revisión de la literatura / Seronegative Myasthenia Gravis: A Literature Review

RESUMEN En 1976 se identificaron varios anticuerpos dirigidos contra el receptor de acetil colina en el suero de los pacientes con miastenia gravis (MG). Sin embargo, luego de unos años, se evidenció que aproximadamente el 20 % de los pacientes con MG generalizada y con evidencia electrofisiológica de un trastorno de la unión neuromuscular, no expresan dichos anticuerpos por radioinmunoensayo (RIA); éstos constituyen los casos de miastenia gravis seronegativa (MGSN). El diagnóstico en estos pacientes es difícil, dada la ausencia de autoanticuerpos detectables en suero y la falta de estudios neurofisiológicos sensibles. Recientemente un nuevo método basado en ensayos celulares muestra un aumento significativo en la detección de miastenia seropositiva, en casos diagnosticados previamente como seronegativos. Este artículo pretende dar un abordaje sobre la fisiopatología de la miastenia gravis seronegativa, así como una actualización de los últimos avances sobre su diagnóstico. También busca hacer una revisión sobre el contexto general actual de esta patología en Colombia.

SUMMARY In 1976 antibodies against acetyl-choline receptor were identified on the serum of patients with myasthenia gravis. However, some years later, it became clear that about 20% of patients with generalized MG and an electro physiologic disorder on the neuromuscular junction did not express these antibodies by radioimmunoassay (RIPA). These cases represent seronegative myasthenia gravis (SNMG). The diagnosis of these patients is difficult, given the absence of detectable autoantibodies on serum and the lack of sensitive neurophysiologic tests. Recently, a new method based on cellular assays shows an increase on detection of seropositive MG from cases, which were initially diagnosed as seronegative. This article reviews the physiopathology of seronegative MG and gives an update on the latest advances concerning its diagnosis. It also hopes to approach the current general context of the illness in Colombia.

A Case of Lambert-Eaton Myasthenic Syndrome with Small-Cell Lung Cancer and Transient Increase in Anti-Acetylcholine-Receptor-Binding Antibody Titer

BACKGROUND: Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic neuromuscular junction disorder that is most frequently associated with small-cell lung cancer (SCLC). The titers of antibodies against voltage-gated calcium channels are frequently increased in LEMS, but only rarely is titer of anti-acetylcholine-receptor-binding antibodies (AChR-abs) increased. CASE REPORT: A 57-year-old male was admitted to our hospital due to dry mouth and eyes and progressive proximal limb weakness of 2 months duration. The results of a repetitive nerve stimulation test disclosed all criteria for the electrophysiological LEMS pattern, and the patient's AChR-abs titer was 0.587 nmol/L. At a follow-up performed 5 years after successful treatment of SCLC and LEMS, his AChR-abs titer had decreased to 0.001 nmol/L. CONCLUSIONS: We suggest that this was a case of transient pseudopositivity of AChR-abs in SCLC with LEMS.

Occupational Neurotoxic Diseases in Taiwan

Occupational neurotoxic diseases have become increasingly common in Taiwan due to industrialization. Over the past 40 years, Taiwan has transformed from an agricultural society to an industrial society. The most common neurotoxic diseases also changed from organophosphate poisoning to heavy metal intoxication, and then to organic solvent and semiconductor agent poisoning. The nervous system is particularly vulnerable to toxic agents because of its high metabolic rate. Neurological manifestations may be transient or permanent, and may range from cognitive dysfunction, cerebellar ataxia, Parkinsonism, sensorimotor neuropathy and autonomic dysfunction to neuromuscular junction disorders. This study attempts to provide a review of the major outbreaks of occupational neurotoxins from 1968 to 2012. A total of 16 occupational neurotoxins, including organophosphates, toxic gases, heavy metals, organic solvents, and other toxic chemicals, were reviewed. Peer-reviewed articles related to the electrophysiology, neuroimaging, treatment and long-term follow up of these neurotoxic diseases were also obtained. The heavy metals involved consisted of lead, manganese, organic tin, mercury, arsenic, and thallium. The organic solvents included n-hexane, toluene, mixed solvents and carbon disulfide. Toxic gases such as carbon monoxide, and hydrogen sulfide were also included, along with toxic chemicals including polychlorinated biphenyls, tetramethylammonium hydroxide, organophosphates, and dimethylamine borane. In addition we attempted to correlate these events to the timeline of industrial development in Taiwan. By researching this topic, the hope is that it may help other developing countries to improve industrial hygiene and promote occupational safety and health care during the process of industrialization.

Occupational Neurotoxic Diseases in Taiwan

Occupational neurotoxic diseases have become increasingly common in Taiwan due to industrialization. Over the past 40 years, Taiwan has transformed from an agricultural society to an industrial society. The most common neurotoxic diseases also changed from organophosphate poisoning to heavy metal intoxication, and then to organic solvent and semiconductor agent poisoning. The nervous system is particularly vulnerable to toxic agents because of its high metabolic rate. Neurological manifestations may be transient or permanent, and may range from cognitive dysfunction, cerebellar ataxia, Parkinsonism, sensorimotor neuropathy and autonomic dysfunction to neuromuscular junction disorders. This study attempts to provide a review of the major outbreaks of occupational neurotoxins from 1968 to 2012. A total of 16 occupational neurotoxins, including organophosphates, toxic gases, heavy metals, organic solvents, and other toxic chemicals, were reviewed. Peer-reviewed articles related to the electrophysiology, neuroimaging, treatment and long-term follow up of these neurotoxic diseases were also obtained. The heavy metals involved consisted of lead, manganese, organic tin, mercury, arsenic, and thallium. The organic solvents included n-hexane, toluene, mixed solvents and carbon disulfide. Toxic gases such as carbon monoxide, and hydrogen sulfide were also included, along with toxic chemicals including polychlorinated biphenyls, tetramethylammonium hydroxide, organophosphates, and dimethylamine borane. In addition we attempted to correlate these events to the timeline of industrial development in Taiwan. By researching this topic, the hope is that it may help other developing countries to improve industrial hygiene and promote occupational safety and health care during the process of industrialization.

Myasthenia Gravis Presenting Hyperacusia and Ptosis

Myasthenia gravis (MG), which is the most common autoimmune neuromuscular junction disorder, is characterized by weakness of musdes and increased fatigability after repetitive use, and recovery after rest. The diagnosis is based on a detailed history, physical examination, and pharmacological, electrophysiological, and immunological testing. Stapedial reflex abnormalities are noted, so the stapedial reflex decay test (SRDT) can be attempted. There are no reports regarding the SRDT in Korea. We report a case of MG presenting hyperacusia and ptosis that was diagnosed by the SRDT. We recommend using the SRDT in the clinical diagnosis of MG.

Myasthenia gravis and pregnancy

A 33 years old multigravida lady presented at 8 weeks of gestation for booking, with a history of previous three caesarean sections. In 1995, her first pregnancy ended up in spontaneous abortion. The development of classical symptoms of MG during her second pregnancy and delayed recovery from nondepolarizing muscle relaxant [used for general anaesthesia] led to the suspicion of MG. The neonate also suffered from transient neonatal MG. Later on, she was investigated and found to have raised anticholinesterase receptor antibodies [117 nmol/L], cholinesterase level [4355 micro /L] and serum anti-DNA [3.9 I.V/ml]. Other antibodies including ANA, AMSA and AMA were negative. The treatment for MG started with an anti-cholinesterase agent in a dose of 60 mg daily. Thymectomy was carried out in 1998 for enlarged thymus gland and her symptoms further improved. Thereafter, the dose of anti-cholinesterase drug was reduced to half i.e., 30 mg daily during subsequent three pregnancies. The present pregnancy was supervised intensively by an obstetrician and neurologist. An elective C. section with bilateral tubal ligation was carried out on term under spinal anaesthesia. A male baby weighing 4 kg was delivered with an APGAR scores of eight at one minute and ten at five minutes. The patient continued her normal oral therapy before and after the operation. Her puerperium was uneventful

Re-evaluation of Repetitive Nerve Stimulation Test in Myasthenia Gravis and Myasthenic Syndrome

BACKGROUND: The repetitive nerve stimulation (RNS) test is a useful tool in the evaluation of neuromuscular transmission disorders. In our laboratory, we frequently use Oh's method, which tests 5 kinds of muscles (flexor carpi ulnaris (FCU), abductor digiti quinti (ADQ), orbicularis oculi, nasalis and trapezius) with 3 kinds of low rate stimulation (LRS) and high rate stimulation (HRS). This method has the advantage of high sensitivity, but is time consuming and painful to patients. So, we tried to reestablish the stage of RNS to overcome this problem and to create a useful test. METHODS: We analyzed RNS data from 369 patients, retrospectively. The number of patients with myasthenia gravis (MG) was 357 and the number with myasthenic syndrome was 12. We compared the sensitivity of individual muscle as well as individual stimulation rate. And we analyzed the results of MG and myasthenic syndrome to verify the usefulness of HRS. RESULTS: The sensitivity of RNS (LRS) was 69.7% in MG (generalized symptom 86.4%, only ocular symptom 40.3%). The sensitivity was higher with 3 pps and 5 pps than with 2 pps, while the exclusion of 2 pps did not affect the sensitivity. We found only 3 cases (1.0%) with post-tetanic exhaustion (PTE) in MG patients with negative results on LRS. The distributions of resting CMAP and post-exercise CMAP were different between MG and myasthenic syndrome. In most cases of myasthenic syndrome, the resting CMAP of ADQ and FCU was below 4.0 mV and post-exercise CMAP of ADQ and FCU was above 50%. CONCLUSIONS: LRS may be done with only 3 and 5 pps, and HRS of the ulnar nerve was helpful only if there was a suspicion of myasthenic syndrome (resting CMAP50%, in ADQ & FCU) or a borderline decremental response in LRS.

Quantitative Change of Repetitive Nerve StimulationTest in Myasthenia Gravis

Repetitive nerve stimulation test (RNS) is an easy and non-invasive test which provides objective for the presence of a myasthenic neuromuscular defect and for monitoring possible improvement through various therapeutic measures, and makes the differentiation of neuromuscular junction disorders. Analysing the RNS test of 45 normal controls and 146 patients with myasthenia gravis quantitatively, the following results obtained. 1. At low rate stimulation, the decremental response upto 2 standard deviation in normal control are 7.1% in orbicularis oculi(~), 7.6% in flexor carpi ulnaris (FCU) and 5.4% in abductor digiti guinti muscle(ADQ). There are two kinds of facilitation noticed: incremental responses at repetitive low stimulation (13.3-14.9%) immediately after tetanic stimulationy and increased mean amplitudes of compound muscle action potentials after exercise(l3-17%). Four minutes after the tetanic stimulation, the decremental responses at low rate stimulation become accentuated slightly even in normal control group. 2. At low rate stimulation. There are singificant decremental decremental responses in patients with myasthenia gravis, but statistically no significant differences are seen in the quantity of decremental responses among 2, 3 and 5/sec rate of stimulation. 3. The pattern and severity of decremental responses at low rate stimulation are depending on the clinical type of generalized myasthenia gravis. There are no decremental responses in FCU or ADQ in ocular type. The decremental responses of oo are greater than that of FCU in mild generalize myasthenia, but the reverse is true in moderate generalized type. 4. Statistically significant post-tetanic facilitation and exhaustion are noticed in patients with generalized myasthenia gravis.

Quantitative Change of Repetitive Nerve StimulationTest in Myasthenia Gravis

Repetitive nerve stimulation test (RNS) is an easy and non-invasive test which provides objective for the presence of a myasthenic neuromuscular defect and for monitoring possible improvement through various therapeutic measures, and makes the differentiation of neuromuscular junction disorders. Analysing the RNS test of 45 normal controls and 146 patients with myasthenia gravis quantitatively, the following results obtained. 1. At low rate stimulation, the decremental response upto 2 standard deviation in normal control are 7.1% in orbicularis oculi(~), 7.6% in flexor carpi ulnaris (FCU) and 5.4% in abductor digiti guinti muscle(ADQ). There are two kinds of facilitation noticed: incremental responses at repetitive low stimulation (13.3-14.9%) immediately after tetanic stimulationy and increased mean amplitudes of compound muscle action potentials after exercise(l3-17%). Four minutes after the tetanic stimulation, the decremental responses at low rate stimulation become accentuated slightly even in normal control group. 2. At low rate stimulation. There are singificant decremental decremental responses in patients with myasthenia gravis, but statistically no significant differences are seen in the quantity of decremental responses among 2, 3 and 5/sec rate of stimulation. 3. The pattern and severity of decremental responses at low rate stimulation are depending on the clinical type of generalized myasthenia gravis. There are no decremental responses in FCU or ADQ in ocular type. The decremental responses of oo are greater than that of FCU in mild generalize myasthenia, but the reverse is true in moderate generalized type. 4. Statistically significant post-tetanic facilitation and exhaustion are noticed in patients with generalized myasthenia gravis.