Pub Date : 2021-11-08DOI: 10.23937/2378-3001/1410115
K. Ajit, Malhotra Vickrant
{"title":"Unusual Simultaneous Occurrence of Cerebral Arterial and Venous Thromboembolism in the Setting of Antithrombin 3 (AT3) Deficiency","authors":"K. Ajit, Malhotra Vickrant","doi":"10.23937/2378-3001/1410115","DOIUrl":"https://doi.org/10.23937/2378-3001/1410115","url":null,"abstract":"","PeriodicalId":14172,"journal":{"name":"International Journal of Neurology and Neurotherapy","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78372648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Endovascular embolization of cerebral aneurysm is common in clinical practice. The rare complication of endovascular embolization is coil misplacement. Most of the reported coil misplacements occur due to premature release of a coil into the cerebral circulation. We report a case of a coil lost into the peripheral circulation due to failed detachment from the micro-catheter at the right place. Case: A young lady without medical history, presented at the emergency department with severe headache. Her consciousness level deteriorated, and her GCS dropped to 5, requiring immediate intubation, sedation and ventilation. Computer tomography and angiography showed a giant supraclinoid aneurysm of the left internal carotid artery. She was taken for endovascular coiling under general anesthesia and one coil was successfully inserted in the aneurysm. During the insertion of the second coil, it was not possible to detach the coil from the micro-catheter, the coil got stuck at the level of the carotid bifurcation and after several failed attempts to remove it, the coil was swept away into the general circulation and went undetected on fluoroscopy. Next day extremity X-ray showed the coil in the left popliteal artery. Patient was taken for angiography, the misplaced coil was successfully removed and the aneurysm was completely embolized. Her condition improved with supportive care and by day 14 she was successfully extubated and discharged home after another week. Conclusion: During embolization coil can fail to get detached from the catheter and can go into the peripheral circulation.
{"title":"Missed Cerebral Coil Found in Peripheral Circulation after Endovascular Embolization: A Rare Complication and Review","authors":"Shaikh Nissar, Nawaz Shoaib, A. Sumayya, Khan Adnan, Alkubaisi Aisha, Momin Umais Zaid, Thabet Abdulnasser","doi":"10.23937/2378-3001/1410112","DOIUrl":"https://doi.org/10.23937/2378-3001/1410112","url":null,"abstract":"Endovascular embolization of cerebral aneurysm is common in clinical practice. The rare complication of endovascular embolization is coil misplacement. Most of the reported coil misplacements occur due to premature release of a coil into the cerebral circulation. We report a case of a coil lost into the peripheral circulation due to failed detachment from the micro-catheter at the right place. Case: A young lady without medical history, presented at the emergency department with severe headache. Her consciousness level deteriorated, and her GCS dropped to 5, requiring immediate intubation, sedation and ventilation. Computer tomography and angiography showed a giant supraclinoid aneurysm of the left internal carotid artery. She was taken for endovascular coiling under general anesthesia and one coil was successfully inserted in the aneurysm. During the insertion of the second coil, it was not possible to detach the coil from the micro-catheter, the coil got stuck at the level of the carotid bifurcation and after several failed attempts to remove it, the coil was swept away into the general circulation and went undetected on fluoroscopy. Next day extremity X-ray showed the coil in the left popliteal artery. Patient was taken for angiography, the misplaced coil was successfully removed and the aneurysm was completely embolized. Her condition improved with supportive care and by day 14 she was successfully extubated and discharged home after another week. Conclusion: During embolization coil can fail to get detached from the catheter and can go into the peripheral circulation.","PeriodicalId":14172,"journal":{"name":"International Journal of Neurology and Neurotherapy","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84418224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-07DOI: 10.23937/2378-3001/1410111
G. BeranRoy
Introduction: This paper reinforces the concept that headaches reside on a continuum with migraine type headache at one end of the spectrum and Tension Type Headache (TTHs) at the other with what used to be referred to as tension/vascular headaches, along that continuum. Background information: This brief overview of headaches is based upon almost half a century of clinical neurological experience by the author, rather than an in depth analysis of definitions and is also dependent upon impressions of patient responses to treatment. Results: Based upon clinical experience, one of the most common complaints that present to the neurologist is that of chronic headache, or headache in general, and so long as the headache is significantly intrusive it is referred to the consultant as a case of migraine even if the evidence favours an alternative headache type such as TTH. Discussion: This paper confirms the concept, demonstrated in previous studies, that there is a continuum spectrum of headache types, with patients moving along that continuum with changing presentations at various times during a long history of headaches.
{"title":"Not All Severe Primary Headaches are Migraines - Tension Type Headaches are Far More Common Yet often Labelled as Migraines","authors":"G. BeranRoy","doi":"10.23937/2378-3001/1410111","DOIUrl":"https://doi.org/10.23937/2378-3001/1410111","url":null,"abstract":"Introduction: This paper reinforces the concept that headaches reside on a continuum with migraine type headache at one end of the spectrum and Tension Type Headache (TTHs) at the other with what used to be referred to as tension/vascular headaches, along that continuum. Background information: This brief overview of headaches is based upon almost half a century of clinical neurological experience by the author, rather than an in depth analysis of definitions and is also dependent upon impressions of patient responses to treatment. Results: Based upon clinical experience, one of the most common complaints that present to the neurologist is that of chronic headache, or headache in general, and so long as the headache is significantly intrusive it is referred to the consultant as a case of migraine even if the evidence favours an alternative headache type such as TTH. Discussion: This paper confirms the concept, demonstrated in previous studies, that there is a continuum spectrum of headache types, with patients moving along that continuum with changing presentations at various times during a long history of headaches.","PeriodicalId":14172,"journal":{"name":"International Journal of Neurology and Neurotherapy","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88022076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-12-31DOI: 10.23937/2378-3001/1410106
O. Serhat, Topcu Hulya
ALS is a rare motor neuron disease. Since surgical procedures exacerbate ALS, surgical procedures are not usually applied except in the necessary cases. Pulmonary complications are the main cause of mortality in ALS patients, because respiratory and swallowing muscles may be affected. Although opioids provide effective analgesia, they are not the best choice in ALS patients because they can cause nausea-vomiting and have negative effects on respiratory functions. Oblique Subcostal Transversus Abdominis Plane Block provides highly effective analgesia in laparoscopic cholecystectomy operations. In this case report, we evaluated the effectiveness of the OSTAP block in ALS patients, which is one of the rare diseases and rarely underwent Laparoscopic Cholecystectomy. As far as we know, this case report is the first and only in literature. Laparoscopic Cholecystectomy was performed under general anesthesia on a 56-year-old male patient. Unilateral OSTAP block (30 ml 0.25%) was applied. The patient's postoperative 10th-hour pain score was 4, and 75 mg diclofenac sodium i.m. administered. The patient did not need any other analgesics. In this case; we detected that the OSTAP block provides effective analgesia.
肌萎缩侧索硬化症是一种罕见的运动神经元疾病。由于外科手术加重了ALS，除非在必要的情况下，通常不采用外科手术。肺部并发症是ALS患者死亡的主要原因，因为呼吸和吞咽肌肉可能受到影响。虽然阿片类药物具有有效的镇痛作用，但由于其可引起恶心呕吐，并对呼吸功能产生负面影响，因此并不是ALS患者的最佳选择。斜肋下腹横面阻滞在腹腔镜胆囊切除术中提供了高效的镇痛效果。在本病例报告中，我们评估了OSTAP阻滞在ALS患者中的有效性，ALS是一种罕见的疾病，很少接受腹腔镜胆囊切除术。据我们所知，这是文献中第一例也是唯一一例。腹腔镜胆囊切除术是一名56岁男性患者在全身麻醉下进行的手术。单侧OSTAP阻滞(30 ml 0.25%)。患者术后第10小时疼痛评分为4，双氯芬酸钠75 mg静脉滴注。患者不需要任何其他镇痛药。在这种情况下;我们发现OSTAP阻滞提供了有效的镇痛作用。
{"title":"Evaluation of Oblique Subcostal Transversus Abdominis Plane Block Effectiveness in Amyotrophic Lateral Sclerosis Patients Undergoing Laparoscopic Cholecystectomy","authors":"O. Serhat, Topcu Hulya","doi":"10.23937/2378-3001/1410106","DOIUrl":"https://doi.org/10.23937/2378-3001/1410106","url":null,"abstract":"ALS is a rare motor neuron disease. Since surgical procedures exacerbate ALS, surgical procedures are not usually applied except in the necessary cases. Pulmonary complications are the main cause of mortality in ALS patients, because respiratory and swallowing muscles may be affected. Although opioids provide effective analgesia, they are not the best choice in ALS patients because they can cause nausea-vomiting and have negative effects on respiratory functions. Oblique Subcostal Transversus Abdominis Plane Block provides highly effective analgesia in laparoscopic cholecystectomy operations. In this case report, we evaluated the effectiveness of the OSTAP block in ALS patients, which is one of the rare diseases and rarely underwent Laparoscopic Cholecystectomy. As far as we know, this case report is the first and only in literature. Laparoscopic Cholecystectomy was performed under general anesthesia on a 56-year-old male patient. Unilateral OSTAP block (30 ml 0.25%) was applied. The patient's postoperative 10th-hour pain score was 4, and 75 mg diclofenac sodium i.m. administered. The patient did not need any other analgesics. In this case; we detected that the OSTAP block provides effective analgesia.","PeriodicalId":14172,"journal":{"name":"International Journal of Neurology and Neurotherapy","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75989261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-29DOI: 10.23937/2378-3001/1410099
M. Guntel, H. Can, Fatma Gok, Goncagul Tangulec, Unal Balikel, Nur Usta Busra
Intracerebral hemorrhage (ICH) (International Classification of Diseases, 9th Revision) is a neurological deficit documented by brain CT or MRI showing the presence of an intracranial bleed in the parenchyma of the brain. ICH is a serious cerebrovascular condition associated with high mortality and morbidity in adults It can be classified as primary and secondary according to etiology. Primary intracranial hemorrhage often develops due to hypertension or amyloid angiopathy. Secondary intracranial hemorrhage causes are often tumor, aneurysm and vascular anomalies. Trauma is the most common reason of seconder ICH. Sildenafil citrate is a potent vasodilator agent used in the treatment of erectile dysfunction. Among its side effects, intracranial hemorrhage is a very rare complication. We present a case of a 54-year-old patient who was brought to the emergency department due to nausea, vomiting and confusion after the use of sildenafil. The patient was diagnosed with intracranial hemorrhage in the setting of sildenafil use after excluding other causes.
{"title":"Intracranial Hemorrhage Associated with Sildenafil Use: A Very Rare Complication","authors":"M. Guntel, H. Can, Fatma Gok, Goncagul Tangulec, Unal Balikel, Nur Usta Busra","doi":"10.23937/2378-3001/1410099","DOIUrl":"https://doi.org/10.23937/2378-3001/1410099","url":null,"abstract":"Intracerebral hemorrhage (ICH) (International Classification of Diseases, 9th Revision) is a neurological deficit documented by brain CT or MRI showing the presence of an intracranial bleed in the parenchyma of the brain. ICH is a serious cerebrovascular condition associated with high mortality and morbidity in adults It can be classified as primary and secondary according to etiology. Primary intracranial hemorrhage often develops due to hypertension or amyloid angiopathy. Secondary intracranial hemorrhage causes are often tumor, aneurysm and vascular anomalies. Trauma is the most common reason of seconder ICH. Sildenafil citrate is a potent vasodilator agent used in the treatment of erectile dysfunction. Among its side effects, intracranial hemorrhage is a very rare complication. We present a case of a 54-year-old patient who was brought to the emergency department due to nausea, vomiting and confusion after the use of sildenafil. The patient was diagnosed with intracranial hemorrhage in the setting of sildenafil use after excluding other causes.","PeriodicalId":14172,"journal":{"name":"International Journal of Neurology and Neurotherapy","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87367779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-17DOI: 10.20944/preprints202004.0303.v1
Júlia Machado Rickli, Gabriela Pomaleski, M. Gonçalves
Objective: Elucidate the main clinical aspects of the CANOMAD spectrum. Methods: Bibliographical review trough databases (PubMed, Google Scholar, Orphanet, Oxford Academic) of articles from 1985 (1) to 2019 and later selection of the most applicable of the above, in order to construct a non-systematic review. Conclusion: CANOMAD is a chronic-ataxic autoimmune neuropathy associated with IgM monoclonal gammopathy. The correct diagnosis of this rare and multi-faceted disease will help optimal treatment.
目的:阐明CANOMAD谱的主要临床特征。方法:通过数据库(PubMed, Google Scholar, Orphanet, Oxford Academic)对1985(1)- 2019年的文章进行文献综述，随后选择上述最适用的文章，构建非系统综述。结论:CANOMAD是一种与IgM单克隆γ病相关的慢性共济失调自身免疫性神经病变。正确诊断这种罕见和多方面的疾病将有助于最佳治疗。
{"title":"CANOMAD: A Multi-Faceted Disease","authors":"Júlia Machado Rickli, Gabriela Pomaleski, M. Gonçalves","doi":"10.20944/preprints202004.0303.v1","DOIUrl":"https://doi.org/10.20944/preprints202004.0303.v1","url":null,"abstract":"Objective: Elucidate the main clinical aspects of the CANOMAD spectrum. Methods: Bibliographical review trough databases (PubMed, Google Scholar, Orphanet, Oxford Academic) of articles from 1985 (1) to 2019 and later selection of the most applicable of the above, in order to construct a non-systematic review. Conclusion: CANOMAD is a chronic-ataxic autoimmune neuropathy associated with IgM monoclonal gammopathy. The correct diagnosis of this rare and multi-faceted disease will help optimal treatment.","PeriodicalId":14172,"journal":{"name":"International Journal of Neurology and Neurotherapy","volume":"80 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91142186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-02-05DOI: 10.23937/2378-3001/1410096
P. Taslim, Wijaya Vincent Ongko
Introduction: Stroke patients commonly experience various medical complications during their rehabilitation stay. Understanding complications in hemorrhagic stroke patients can determine the patient’s prognosis. Aim: This study aimed to explore complications as prognostic factors among patients with hemorrhagic stroke. Methods: This was an observational analytic study with retrospective design. We analyzed the medical records of 480 patients admitted with hemorrhagic stroke between 2017 and 2018 at Bethesda Hospital, Indonesia. Disability, mortality, and length of stay (LoS) were assessed as clinical outcomes for this study. Multivariate logistic regression was used to analyze the data. Results: The data were obtained from 480 patients with hemorrhagic stroke that majority of males (58.5%), with ≤ 60-years-old (52.3%), stroke onset > 3 hours (87.5%), and had stroke for the first time (82.9%). The most common complications were GI tract bleeding (19.8%), whereas the least was decubitus ulcer (1.5%). There were 25.8% patients died during hospitalization period. Among 356 survivors, there were no significant prognosis factors of disability in subjects. Logistic regression found stroke onset ≥ 3 hours (OR: 0.34; 95% CI: 0.19-0.59; p ≤ 0.001) and GI tract bleeding (OR: 30.8; 95% CI: 16.93-55.88; p ≤ 0.001) to be an independent predictors of mortality in hemorrhagic stroke, whereas GI tract bleeding (OR: 0.54; 95% CI: 0.31-0.95; p = 0.03) and UTI (OR: 4.73; 95% CI: 1.11-20.1; p = 0.04) were also an independent predictors of prolonged length of stay in hemorrhagic stroke. Conclusion: This study identify complications as prognostic factors in hemorrhagic stoke patients. Stroke onset > 3 hours, GI tract bleeding, and UTI were independent predictors of poor prognosis in hemorrhagic stroke. There was no prognosis factor that affects disability in subjects.
{"title":"Complications as Poor Prognostic Factors in Patients with Hemorrhagic Stroke: A Hospital-Based Stroke Registry","authors":"P. Taslim, Wijaya Vincent Ongko","doi":"10.23937/2378-3001/1410096","DOIUrl":"https://doi.org/10.23937/2378-3001/1410096","url":null,"abstract":"Introduction: Stroke patients commonly experience various medical complications during their rehabilitation stay. Understanding complications in hemorrhagic stroke patients can determine the patient’s prognosis. Aim: This study aimed to explore complications as prognostic factors among patients with hemorrhagic stroke. Methods: This was an observational analytic study with retrospective design. We analyzed the medical records of 480 patients admitted with hemorrhagic stroke between 2017 and 2018 at Bethesda Hospital, Indonesia. Disability, mortality, and length of stay (LoS) were assessed as clinical outcomes for this study. Multivariate logistic regression was used to analyze the data. Results: The data were obtained from 480 patients with hemorrhagic stroke that majority of males (58.5%), with ≤ 60-years-old (52.3%), stroke onset > 3 hours (87.5%), and had stroke for the first time (82.9%). The most common complications were GI tract bleeding (19.8%), whereas the least was decubitus ulcer (1.5%). There were 25.8% patients died during hospitalization period. Among 356 survivors, there were no significant prognosis factors of disability in subjects. Logistic regression found stroke onset ≥ 3 hours (OR: 0.34; 95% CI: 0.19-0.59; p ≤ 0.001) and GI tract bleeding (OR: 30.8; 95% CI: 16.93-55.88; p ≤ 0.001) to be an independent predictors of mortality in hemorrhagic stroke, whereas GI tract bleeding (OR: 0.54; 95% CI: 0.31-0.95; p = 0.03) and UTI (OR: 4.73; 95% CI: 1.11-20.1; p = 0.04) were also an independent predictors of prolonged length of stay in hemorrhagic stroke. Conclusion: This study identify complications as prognostic factors in hemorrhagic stoke patients. Stroke onset > 3 hours, GI tract bleeding, and UTI were independent predictors of poor prognosis in hemorrhagic stroke. There was no prognosis factor that affects disability in subjects.","PeriodicalId":14172,"journal":{"name":"International Journal of Neurology and Neurotherapy","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81195261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-14DOI: 10.23937/2378-3001/1410092
M RiveraVictor
This paper describes a complicated history taken place during World War II (WWII) when military intentions for acquiring biological weapon superiority knowledge was obtained in some cases through atrocious investigations in human beings disregarding ethical and moral principles. After the war, Murray Sanders (1910-1988), a young military officer and American scientist became incidentally entwined with the U.S. military concern over the Japanese bacteriological knowledge, unbeknown by the Allies that was being acquired through human experiments. In a second stage of his career (between 1949 and 1983), Sanders investigated the potential therapeutic characteristics of snake venom, obtained several U.S. patents on the formulation and an Investigational New Drug (IND) license from the Food and Drug Administration (FDA). While he was well-intentioned and cared for his patients, Sanders utilized protocols non-sanctioned by Independent Ethics Committees and openly administered detoxified snake venom neurotoxin or Modified Neurotoxin (MNT) to patients with poliomyelitis and later used it in Amyotrophic Lateral Sclerosis (ALS). While Sanders reported “partial” efficacy of MNT in ALS this was not confirmed with placebo-controlled, IRB-approved clinical trials. Two well-designed placebo-controlled clinical trials performed by independent institutions sanctioned by the FDA and approved by their respective Institutional Review Boards did not yield positive results. Findings were reported in the neurological literature. Later in life Sanders was requested to testify in a Congressional Hearing on the WWII Japanese bacteriological warfare experiments and the U.S. strategy to condone culpability of war crimes in exchange for military information. This article reflects on a scientific effort spanning through several epochs and personae interacting with diverse philosophies and different objectives performing research in human beings. *Corresponding author: Victor M Rivera, MD, FAAN, Distinguished Emeritus Professor, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA ReView ARticle
本文描述了第二次世界大战期间发生的一段复杂的历史，在某些情况下，获取生物武器优势知识的军事意图是通过对人类的残暴调查而获得的，无视伦理和道德原则。战争结束后，默里·桑德斯(Murray Sanders, 1910-1988)，一位年轻的军官和美国科学家，偶然地卷入了美国军方对日本人的细菌知识的关注中，这些知识是盟军通过人体实验获得的，却不为人知。在他职业生涯的第二阶段(1949年至1983年)，桑德斯研究了蛇毒的潜在治疗特性，获得了几项配方的美国专利，并获得了食品和药物管理局(FDA)的研究新药(IND)许可证。虽然他的初衷是好的，也很关心他的病人，但桑德斯采用了未经独立伦理委员会批准的方案，公开给脊髓灰质炎患者使用解毒的蛇毒神经毒素或改良神经毒素(MNT)，后来又将其用于肌萎缩性侧索硬化症(ALS)。虽然Sanders报告了MNT对ALS的“部分”疗效，但这并没有得到安慰剂对照、irb批准的临床试验的证实。两个设计良好的安慰剂对照临床试验由FDA批准的独立机构进行，并由各自的机构审查委员会批准，但没有产生积极的结果。研究结果已在神经学文献中报道。后来，桑德斯被要求在国会听证会上就二战日本细菌战实验和美国宽恕战争罪行以换取军事情报的战略作证。这篇文章反映了跨越几个时代和人物的科学努力，与不同的哲学和不同的目标相互作用，在人类身上进行研究。*通讯作者:Victor M Rivera，医学博士，FAAN，美国德克萨斯州休斯顿贝勒医学院神经内科名誉教授
{"title":"Biological Warfare and Snake Venom for Poliomyelitis and ALS: The Little Known Entwined History of Failed Ethics and a Reasonable Therapeutic Hypothesis","authors":"M RiveraVictor","doi":"10.23937/2378-3001/1410092","DOIUrl":"https://doi.org/10.23937/2378-3001/1410092","url":null,"abstract":"This paper describes a complicated history taken place during World War II (WWII) when military intentions for acquiring biological weapon superiority knowledge was obtained in some cases through atrocious investigations in human beings disregarding ethical and moral principles. After the war, Murray Sanders (1910-1988), a young military officer and American scientist became incidentally entwined with the U.S. military concern over the Japanese bacteriological knowledge, unbeknown by the Allies that was being acquired through human experiments. In a second stage of his career (between 1949 and 1983), Sanders investigated the potential therapeutic characteristics of snake venom, obtained several U.S. patents on the formulation and an Investigational New Drug (IND) license from the Food and Drug Administration (FDA). While he was well-intentioned and cared for his patients, Sanders utilized protocols non-sanctioned by Independent Ethics Committees and openly administered detoxified snake venom neurotoxin or Modified Neurotoxin (MNT) to patients with poliomyelitis and later used it in Amyotrophic Lateral Sclerosis (ALS). While Sanders reported “partial” efficacy of MNT in ALS this was not confirmed with placebo-controlled, IRB-approved clinical trials. Two well-designed placebo-controlled clinical trials performed by independent institutions sanctioned by the FDA and approved by their respective Institutional Review Boards did not yield positive results. Findings were reported in the neurological literature. Later in life Sanders was requested to testify in a Congressional Hearing on the WWII Japanese bacteriological warfare experiments and the U.S. strategy to condone culpability of war crimes in exchange for military information. This article reflects on a scientific effort spanning through several epochs and personae interacting with diverse philosophies and different objectives performing research in human beings. *Corresponding author: Victor M Rivera, MD, FAAN, Distinguished Emeritus Professor, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA ReView ARticle","PeriodicalId":14172,"journal":{"name":"International Journal of Neurology and Neurotherapy","volume":"126 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76152979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-23DOI: 10.23937/2378-3001/1410091
Anand Inder S, Konstam Marvin A, Ardell Jeffrey L, Libbus Imad, DiCarlo Lorenzo A, Mann Douglas L
Background: Vagus nerve stimulation (VNS) is used currently in the management of drug-refractory epilepsy (DRE), and is in development for treating chronic heart failure (HF). HF is accompanied by autonomic nervous system (ANS) dysfunction, consisting of sustained sympathetic hyper-activation and withdrawal of parasympathetic tone, and associated with progressive worsening of cardiovascular (CV) function and increased morbidity and mortality. We sought to compare how VNS is utilized for DRE and may potentially be employed for HF. Methods: A search was conducted in PubMed for all published articles using the search terms “vagus” OR “vagal” OR “VNS” AND “epilepsy”, and a separate search used similar search terms AND “heart failure”. Further filtering yielded the articles available as free full text, and clinical trial, prospective study, and retrospective study publications. The final selection of clinical trial/study publications in epilepsy or HF was based upon at least 3 months of follow-up and exclusion of pediatric studies. Additional information was obtained subsequently from references within these publications, and technical manuals available in the public domain. Results: For DRE, VNS is administered via the left cervical vagus nerve (CVN), and directed toward the central nervous system (CNS). No known biomarkers exist currently for real-time VNS adjustment. VNS is titrated empirically, using large and infrequent adjustments of VNS intensity and based upon achieving long term reduction in seizure frequency (RSF) and/or reaching the maximum tolerated VNS intensity. A significantly greater mean RSF has been observed after 3 months of VNS delivery using pulse frequency 30 Hz and duty cycle 9% (30 seconds on, 5 minutes off) when compared to using 1 Hz and duty cycle 14% (30 seconds on, 3 minutes off). A further reduction of mean RSF has been observed after 12 months by increasing the pulse frequency at 3 months from 1 to 30 Hz. For HF, VNS has been administered via the left or right CVN, targeting both the CNS and/or peripheral hierarchical autonomic reflex arcs that control cardiovascular function. Real-time changes in heart rate dynamics (HR and HR variability) have served as a biomarker of ANS engagement (ANSE) for titration. Titration to ANSE has been completed in 2.5 (median; range 1.6-3.6) months using 10 Hz and duty cycle 23% (18 seconds on, 1 minute off), using smaller and more frequent adjustments of VNS intensity, and has been associated with significant improvements after 6 months in HR, HR variability, CV function, and HF symptoms. Use of 1 Hz may have less clinical efficacy than occurs with a higher pulse frequency, however, intolerable side effects have occurred before ANSE using 20 Hz. Conclusions: Neuromodulation for the treatment of epilepsy and HF is not a one-size-fits-all therapy. The magnitude of long term reduction of seizure frequency in DRE, and improvements in function and symptoms in HF, may have a potential dose-depe
背景:迷走神经刺激(VNS)目前用于治疗药物难治性癫痫(DRE)，并且正在开发用于治疗慢性心力衰竭(HF)。HF伴有自主神经系统(ANS)功能障碍，包括持续的交感神经过度激活和副交感神经张力的戒除，并伴有心血管(CV)功能的进行性恶化和发病率和死亡率的增加。我们试图比较VNS如何用于DRE和可能用于HF。方法:在PubMed中使用搜索词“迷走神经”或“迷走神经”或“迷走神经麻痹”和“癫痫”对所有已发表的文章进行搜索，并使用类似的搜索词和“心力衰竭”进行单独搜索。进一步筛选得到免费全文、临床试验、前瞻性研究和回顾性研究出版物。癫痫或心衰临床试验/研究出版物的最终选择是基于至少3个月的随访和排除儿科研究。后来从这些出版物的参考文献和公共领域的技术手册中获得了更多的资料。结果:对于DRE, VNS经左颈迷走神经(CVN)给药，并直接作用于中枢神经系统(CNS)。目前还没有已知的生物标志物用于实时调节VNS。根据经验滴定VNS，使用大而不频繁的VNS强度调整，并基于实现癫痫发作频率(RSF)的长期降低和/或达到最大耐受的VNS强度。与脉冲频率为1 Hz、占空比为14%(30秒开，3分钟关)的VNS相比，脉冲频率为30 Hz、占空比为9%(30秒开，5分钟关)的VNS传递3个月后的平均RSF明显更高。12个月后，通过在3个月时将脉冲频率从1赫兹增加到30赫兹，观察到平均RSF进一步降低。对于HF, VNS通过左或右CVN给药，靶向控制心血管功能的CNS和/或外周分层自主反射弧。心率动态的实时变化(HR和HR变异性)被用作ANS参与(ANSE)的生物标志物，用于滴定。ANSE的滴定在2.5(中位数;范围1.6-3.6)个月，使用10hz，占空比23%(开启18秒，关闭1分钟)，使用更小和更频繁的VNS强度调整，并与6个月后HR, HR变异性，CV功能和HF症状的显着改善相关。使用1hz的脉冲频率可能比使用更高的脉冲频率的临床疗效差，然而，在使用20hz的脉冲频率之前，已经发生了无法忍受的副作用。结论:神经调节治疗癫痫和心衰并不是一种万能的治疗方法。DRE患者癫痫发作频率的长期降低幅度，以及HF患者功能和症状的改善程度，可能与VNS传递的强度存在潜在的剂量依赖关系。然而，用于这些疾病的VNS在神经靶点、用于滴定的技术平台和范例以及上调VNS所需的时间和频率方面存在差异。*通讯作者:Inder S Anand, MD, FRCP, DPhil (Oxon)，明尼苏达大学VA医学中心心脏病科，心脏病学111-C, One Veterans Drive, Minneapolis, MN 55417, USA，电话:+1-(612)-467-3663，传真:+1-(612)970-5899
{"title":"Neuromodulation for Drug-Refractory Epilepsy and Chronic Heart Failure: Targets, Delivery, Composition and Titration","authors":"Anand Inder S, Konstam Marvin A, Ardell Jeffrey L, Libbus Imad, DiCarlo Lorenzo A, Mann Douglas L","doi":"10.23937/2378-3001/1410091","DOIUrl":"https://doi.org/10.23937/2378-3001/1410091","url":null,"abstract":"Background: Vagus nerve stimulation (VNS) is used currently in the management of drug-refractory epilepsy (DRE), and is in development for treating chronic heart failure (HF). HF is accompanied by autonomic nervous system (ANS) dysfunction, consisting of sustained sympathetic hyper-activation and withdrawal of parasympathetic tone, and associated with progressive worsening of cardiovascular (CV) function and increased morbidity and mortality. We sought to compare how VNS is utilized for DRE and may potentially be employed for HF. Methods: A search was conducted in PubMed for all published articles using the search terms “vagus” OR “vagal” OR “VNS” AND “epilepsy”, and a separate search used similar search terms AND “heart failure”. Further filtering yielded the articles available as free full text, and clinical trial, prospective study, and retrospective study publications. The final selection of clinical trial/study publications in epilepsy or HF was based upon at least 3 months of follow-up and exclusion of pediatric studies. Additional information was obtained subsequently from references within these publications, and technical manuals available in the public domain. Results: For DRE, VNS is administered via the left cervical vagus nerve (CVN), and directed toward the central nervous system (CNS). No known biomarkers exist currently for real-time VNS adjustment. VNS is titrated empirically, using large and infrequent adjustments of VNS intensity and based upon achieving long term reduction in seizure frequency (RSF) and/or reaching the maximum tolerated VNS intensity. A significantly greater mean RSF has been observed after 3 months of VNS delivery using pulse frequency 30 Hz and duty cycle 9% (30 seconds on, 5 minutes off) when compared to using 1 Hz and duty cycle 14% (30 seconds on, 3 minutes off). A further reduction of mean RSF has been observed after 12 months by increasing the pulse frequency at 3 months from 1 to 30 Hz. For HF, VNS has been administered via the left or right CVN, targeting both the CNS and/or peripheral hierarchical autonomic reflex arcs that control cardiovascular function. Real-time changes in heart rate dynamics (HR and HR variability) have served as a biomarker of ANS engagement (ANSE) for titration. Titration to ANSE has been completed in 2.5 (median; range 1.6-3.6) months using 10 Hz and duty cycle 23% (18 seconds on, 1 minute off), using smaller and more frequent adjustments of VNS intensity, and has been associated with significant improvements after 6 months in HR, HR variability, CV function, and HF symptoms. Use of 1 Hz may have less clinical efficacy than occurs with a higher pulse frequency, however, intolerable side effects have occurred before ANSE using 20 Hz. Conclusions: Neuromodulation for the treatment of epilepsy and HF is not a one-size-fits-all therapy. The magnitude of long term reduction of seizure frequency in DRE, and improvements in function and symptoms in HF, may have a potential dose-depe","PeriodicalId":14172,"journal":{"name":"International Journal of Neurology and Neurotherapy","volume":"88 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78307873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-18DOI: 10.23937/2378-3001/1410090
Konishi Tetsuro
Anti-muscle-specific kinase (MuSK) antibody positive generalized myasthenia gravis (MuSK-MG) is an autoimmune disease, in which deterioration of myasthenic symptoms may occur by cholinesterase inhibitor (ChE-I) treatment. Salbutamol, a sympathetic β2 receptor agonist, was an effective therapeutic drug in congenital myasthenic syndrome patients with MuSK gene abnormalities and in MuSK-MG animal model. Salbutamol was attempted to treat a female MuSK-MG patient who did not respond to ChE-I. Any acute benefit of salbutamol was not observed but her myasthenic symptoms gradually improved over a year without adversive effects. Salbutamol may be a therapeutic drug to alleviate myasthenic symptoms in MuSK-MG patients.
{"title":"A Female Patient with Anti-Muscle-Specific Kinase Antibody Positive Generalized Myasthenia Gravis Responded to Salbutamol but not Pyridostigmine: A Case Report","authors":"Konishi Tetsuro","doi":"10.23937/2378-3001/1410090","DOIUrl":"https://doi.org/10.23937/2378-3001/1410090","url":null,"abstract":"Anti-muscle-specific kinase (MuSK) antibody positive generalized myasthenia gravis (MuSK-MG) is an autoimmune disease, in which deterioration of myasthenic symptoms may occur by cholinesterase inhibitor (ChE-I) treatment. Salbutamol, a sympathetic β2 receptor agonist, was an effective therapeutic drug in congenital myasthenic syndrome patients with MuSK gene abnormalities and in MuSK-MG animal model. Salbutamol was attempted to treat a female MuSK-MG patient who did not respond to ChE-I. Any acute benefit of salbutamol was not observed but her myasthenic symptoms gradually improved over a year without adversive effects. Salbutamol may be a therapeutic drug to alleviate myasthenic symptoms in MuSK-MG patients.","PeriodicalId":14172,"journal":{"name":"International Journal of Neurology and Neurotherapy","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73268090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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