Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Hospital Course, Confounders, and Medications.

The convergence of an interdisciplinary team of neurocritical care specialists to organize the Curing Coma Campaign is the first effort of its kind to coordinate national and international research efforts aimed at a deeper understanding of disorders of consciousness (DoC). This process of understanding includes translational research from bench to bedside, descriptions of systems of care delivery, diagnosis, treatment, rehabilitation, and ethical frameworks. The description and measurement of varying confounding factors related to hospital care was thought to be critical in furthering meaningful research in patients with DoC. Interdisciplinary hospital care is inherently varied across geographical areas as well as community and academic medical centers. Access to monitoring technologies, specialist consultation (medical, nursing, pharmacy, respiratory, and rehabilitation), staffing resources, specialty intensive and acute care units, specialty medications and specific surgical, diagnostic and interventional procedures, and imaging is variable, and the impact on patient outcome in terms of DoC is largely unknown. The heterogeneity of causes in DoC is the source of some expected variability in care and treatment of patients, which necessitated the development of a common nomenclature and set of data elements for meaningful measurement across studies. Guideline adherence in hemorrhagic stroke and severe traumatic brain injury may also be variable due to moderate or low levels of evidence for many recommendations. This article outlines the process of the development of common data elements for hospital course, confounders, and medications to streamline definitions and variables to collect for clinical studies of DoC.

Stroke Care during the COVID-19 Pandemic: International Expert Panel Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. SUMMARY: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.

Comparison of the European and Japanese guidelines for the management of ischemic stroke.

BACKGROUND: Different aspects of acute stroke management and strategies for stroke prevention derive from two viewpoints: specific traditional and historical backgrounds and evidence-based medicine from modern randomized controlled trials (RCTs), meta-analysis and authorized clinical practice guidelines (GLs). Regarding stroke, GLs have been published by national and international organizations in different languages, most frequently in English. Cerebrovascular Diseases published the European GLs for the management of ischemic stroke and transient ischemic attacks in 2003, with an update in 2008. At about the same time (in 2004), the first Japanese GLs for the management of stroke appeared in Japanese. The first English version of the updated Japanese GLs was published only in 2011 and included differently approved drugs and drug dosages as compared with other American or European countries. METHODS: Since 2011, the authors have met repeatedly and have compared the latest versions of published European and Japanese GLs for ischemic and hemorrhagic strokes. Many aspects have only been addressed in one but left out in the other GLs, which consequently founded the basis for the comparison. Classification of evidence levels and recommendation grades defined by the individual committees differed between both original GLs. RESULTS: Aspects of major importance were surprisingly similar and hence did not need extensive interpretation. Other aspects of ischemic stroke management differed significantly, e.g. the dosage of recombinant tissue plasminogen activator approved in Japan is lower (0.6 mg/kg) than in Europe (0.9 mg/kg), which derived from different practices in cardiovascular treatment prior to the design of acute ischemic stroke RCTs. Furthermore, comedication with neuroprotective agents (edaravone), intravenous anticoagulants (argatroban) or antiplatelet agents within 1-2 days after stroke onset is recommended in Japan but not in Europe. For cardioembolic stroke prevention, a major difference consists in a higher international normalized ratio target (2.0-3.0) in younger subjects versus in those >70 years (1.6-2.6), without age restrictions in Europe. CONCLUSION: This brief survey - when compared with the lengthy original recommendations - provides a stimulating basis for an extended interest among Japanese and European stroke clinicians to learn from their individual experiences and to strengthen efforts for joint cooperation in treating and preventing stroke all around the globe.

Comparison of the European and Japanese guidelines for the acute management of intracerebral hemorrhage.

BACKGROUND: Different aspects of acute stroke management and strategies for stroke prevention derive from two viewpoints: specific traditional and historical backgrounds and evidence-based medicine from modern randomized controlled trials (RCTs), meta-analysis and authorized clinical practice guidelines (GLs). Regarding intracerebral hemorrhage (ICH), Cerebrovascular Diseases published the 2006 European stroke initiative recommendations for the management of ICH. In 2009, the revised Japanese GLs for the management of stroke, including that of ICH, appeared in Japanese. Whereas GLs for the prevention and treatment of ischemic stroke were presented in detail, recommendations with regard to ICH are relatively rare both in Japan and Europe. METHODS: Since 2011, the authors have met repeatedly and have compared the latest versions of published European and Japanese GLs for ischemic and hemorrhagic strokes. Many aspects have only been addressed in one but left out in the other GLs, which consequently founded the basis for the comparison. Classification of evidence levels and recommendation grades defined by the individual committees differed between both original GLs. RESULTS: Aspects of major importance were similar and hence did not need extensive interpretation, mostly due to a lack of evidence from appropriate RCTs worldwide. The target level to which systolic blood pressure should be lowered is quite high; <170 mm Hg for patients with known hypertension in Europe and <180 mm Hg in Japan. The results of ongoing clinical trials are awaited for the optimal target level and optimal medications. Concerning ICH associated with oral anticoagulant therapy, both guidelines give similar recommendations, namely that anticoagulation should be discontinued and the international normalized ratio of prothrombin time should be normalized with prothrombin complex concentrate or fresh-frozen plasma and additional vitamin K. Patients with ICH were treated surgically, often based on individual decisions - more frequently in Japan, depending on the association with hypertension. Patients with large or intraventricular bleedings were only treated if a life-saving performance was considered, irrespective of the neurological outcome. Infra- and supratentorial differences were similarly addressed in both GLs. CONCLUSION: This brief survey - when compared with the lengthy original recommendations - provides a stimulating basis for an extended interest among Japanese and European stroke clinicians to learn from their individual experiences and to strengthen efforts for joint cooperation in treating and preventing stroke all around the globe.

Effects of white matter hyperintensities on isolated executive function assessed by the Trail Making Test.

BACKGROUND: White matter hyperintensities (WMHs) on MRI are associated with cognitive dysfunction, particularly slow processing speed and executive dysfunction. However, it is not clear whether WMHs burden affects isolated executive function independent of aging when WMHs are assessed separately in periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH). PURPOSE: To assess the relationship between the degree of WMHs and the performance on the Trail Making Test (TMT), which can evaluate isolated ability of set-shifting and working memory. METHODS: 74 participants who visited our memory clinic and underwent the TMT subtests (TMT-A and TMT-B) and the Mini-Mental State Examination (MMSE). All subjects performed the TMT within the time limits and their MMSE scores were 24 or higher, and they were diagnosed as having normal cognition or mild cognitive impairment. The extent of PVH and DSWMH was graded from 0 to 3 using the Fazekas scale. We obtained testing time to complete the TMT-A and TMT-B, and calculated TMT-B minus TMT-A. We performed correlation analyses between the degree of WMHs and the time measures of the TMT subtests with adjustment of age. RESULTS: Average scores of the MMSE were not different among the groups either by PVH grade or by DSWMH grade. In contrast, average time required for the TMT-A, TMT-B, and TMT-B minus TMT-A increased along with exacerbation of PVH and DSWMH grade. After the adjustment of age we found significant association between only DSWMH grade and the time difference of TMT-B minus TMT-A. CONCLUSIONS: Exacerbation of PVH and DSWMH differentially affected isolated executive functions assessed by the TMT subtests independent of age and general cognitive function.

Proposal of new diagnostic criteria for fatal familial insomnia.

BACKGROUND: The understanding of fatal familial insomnia (FFI), a rare neurodegenerative autosomal dominant prion disease, has improved in recent years as more cases were reported. This work aimed to propose new diagnostic criteria for FFI with optimal sensitivity, specificity, and likelihood ratio. METHODS: An international group of experts was established and 128 genetically confirmed FFI cases and 281 non-FFI prion disease controls are enrolled in the validation process. The new criteria were proposed based on the following steps with two-round expert consultation: (1) Validation of the 2018 FFI criteria. (2) Diagnostic item selection according to statistical analysis and expert consensus. (3) Validation of the new criteria. RESULTS: The 2018 criteria for possible FFI had a sensitivity of 90.6%, a specificity of 83.3%, with a positive likelihood ratio (PLR) of 5.43, and a negative likelihood ratio (NLR) of 0.11; and the probable FFI criteria had a sensitivity of 83.6%, specificity of 92.9%, with a PLR of 11.77, and a NLR of 0.18. The new criteria included more specific and/or common clinical features, two exclusion items, and summarized a precise and flexible diagnostic hierarchy. The new criteria for possible FFI had therefore reached a better sensitivity and specificity (92.2% and 96.1%, respectively), a PLR of 23.64 and a NLR of 0.08, whereas the probable FFI criteria showed a sensitivity of 90.6%, a specificity of 98.2%, with a PLR of 50.33 and a NLR of 0.095. CONCLUSIONS: We propose new clinical diagnostic criteria for FFI, for a better refining of the clinical hallmarks of the disease that ultimately would help an early recognition of FFI and a better differentiation from other prion diseases.

[Neurological Manifestations of COVID-19 and Work-up at the Emergency Room and the Intensive Care Unit].

The global pandemic due to the Coronavirus Disease 2019 (COVID-19) has placed tremendous strain on healthcare services. This review provides guidance to neurologists on the appropriate management of neurological and neurocritical conditions and diseases during the COVID-19 pandemic in the emergency room and the intensive care unit. The guidance is based on official recommendations and manuals that were urgently produced by the international and domestic societies with the contributions of an expert panel including this author.

Postpublication external review of the Japanese guidelines for the management of stroke 2004.

BACKGROUND AND PURPOSE: Many guidelines for management of stroke have been published throughout the world, but no postpublication external review of any set of stroke guidelines by users, using standard checklists, has been reported. The purpose of this article is to present the results of an external review of the Japanese Guidelines for the Management of Stroke 2004, conducted several months postpublication. METHODS: Forty-one evaluators, who had not been involved in developing the guidelines, were selected from representative stroke centers and institutions in Japan. They consisted of 30 physicians including 22 stroke specialists, and 11 nurse practitioners. Three standard checklists, ie, Appraisal of Guidelines for Research and Evaluation (AGREE) instrument, checklist by Shaneyfelt et al, and the Conference on Guideline Standardization (COGS) checklist, were used. RESULTS: Confidence ratios according to the AGREE checklist were 75%, 77%, and 86% for stroke specialists, physicians other than stroke specialists, and nurse practitioners, respectively. The average scores were 2.98, 3.13, and 3.29, [corrected] respectively. The confidence ratios according to the checklist by Shaneyfelt et al were 72%, 73% and 86% respectively, and those for the COGS checklist were 66%, 74%, and 91%, respectively. CONCLUSIONS: Although it is impossible to compare our results with those for other stroke guidelines, because none of them has been externally reviewed by users postpublication, our results seem better than those for published guidelines for treatment of other diseases in Japan. These results should be helpful in the process of updating stroke guidelines in Japan and elsewhere.

[The Japanese Guidelines for the Management of Stroke 2007 and medical professionalism].

In 2004, we published the first Japanese Guidelines for the Management of Stroke which were evidence-based and took into consideration of the differences in races and therapeutic agents between Japan and other countries, and also, employed the detailed, lots of evidences from Japan. For the renewal of this Guideline, the new Joint Committee on Guidelines for the Management of Stroke was established (Chairperson: Yukito Shinohara, Vice-Chairpersons: Akira Ogawa, Yasuo Katayama, Norihiro Suzuki, Akio Kimura, Clinical Epidemiology: Hideki Origasa, Secretariat-General: Masao Nagayama). Approximately 120 representative authorities were selected from five stroke-related societies in Japan. The committee is composed of seven groups which take charge of stroke general, cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, asymptomatic cerebrovascular diseases, other cerebrovascular diseases, or rehabilitation, respectively. On the other hands, in recent years, medical professionalism has been faced a crisis and scrutinized by physicians, patients, and the media. Because the author is also involved in the activity of the committee for the medical professionalism by the Fellows' Association of the Japanese Society of Internal Medicine, recent concepts regarding the relationship between medical professionalism and guideline were reviewed, and the critical roles of a physician in the process of consensus development for clinical guideline determination were emphasized.

Novel clinical features of nonconvulsive status epilepticus.

Nonconvulsive status epilepticus (NCSE) has rapidly expanded from classical features such as staring, repetitive blinking, chewing, swallowing, and automatism to include coma, prolonged apnea, cardiac arrest, dementia, and higher brain dysfunction, which were demonstrated mainly after the 2000s by us and other groups. This review details novel clinical features of NCSE as a manifestation of epilepsy, but one that is underdiagnosed, with the best available evidence. Also, we describe the new concept of epilepsy-related organ dysfunction (Epi-ROD) and a novel electrode and headset which enables prompt electroencephalography.

[Case of Marfan's syndrome with anterior sacral meningocele along with recurring bacterial meningitis].

We reported a 46-year-old woman with Marfan's syndrome exhibiting an incomplete Currarino triad and recurrent bacterial meningitis which recurred three times in about six months. An anterior sacral meningocele (ASM) was noted in a lumbar MRI, and multiple bone defects in the sacrum were noted in 3D-CT. Surgical approach to prevent the recurrence of infection was limited to plasty for the meningocele, but no meningitis has been observed for two years. Radical surgery should be considered in cases with ASM who recurred bacterial meningitis.

Critical role of the "Doctor-Heli" system on cerebral infarction in the superacute stage--report of a outstanding pilot case.

In Japan, the physician staffed helicopter ambulance system, "Doctor-Heli" System, was first founded in our University Hospital in 1999. In this system, a helicopter is based at an Emergency Medical Center at all times and dispatch with both emergency physicians and a nurse upon a request by paramedics. This system has made possible a critically earlier development of the initial management at the point of care and rapid transport to the hospital. We presented the case suffering from acute cerebral infarction was transported by the "Doctor-Heli" and received the intervention for thrombolysis successfully. It was less than three hours from the onset to the completion of the intervention. The "DoctorHeli" system has a potential benefit for patients with acute cerebral infarction because of it enables quite early clinical diagnosis and rapid transport.

Eosinophilic pleurisy induced by dantrolene.

A 70-year-old male developed eosinophilic pleurisy fifteen years after dantrolene sodium had been started for his spastic paraplegia due to spinocerebellar degeneration. Drug lymphocyte stimulation test (DLST) for dantrolene was positive. After discontinuance of dantrolene, pleural effusion gradually decreased and inflammatory reaction improved. During two-year observation, we have found no relapse of pleurisy without special medication. We present this case and compare this case with other 10 reported cases.