Emergency medical service response for cases of stroke-suspected seizure: A population-based study.

OBJECTIVES: We evaluated the on-scene time of emergency medical services (EMS) for cases where discrimination between acute stroke and epileptic seizures at the initial examination was difficult and identified factors linked to delays in such scenarios. MATERIALS AND METHODS: A retrospective review of cases with suspected seizure using the EMS database of fire departments across six Japanese cities between 2016 and 2021 was conducted. Patient classification was based on transport codes. We defined cases with stroke-suspected seizure as those in whom epileptic seizure was difficult to differentiate from stroke and evaluated their EMS on-scene time compared to those with epileptic seizures. RESULTS: Among 30,439 cases with any seizures, 292 cases of stroke-suspected seizure and 8,737 cases of epileptic seizure were included. EMS on-scene time in cases of stroke-suspected seizure was shorter than in those with epileptic seizure after propensity score matching (15.1±7.2 min vs. 17.0±9.0 min; p = 0.007). Factors associated with delays included transport during nighttime (odds ratio [OR], 1.73, 95 % confidence interval [CI] 1.02-2.93, p = 0.041) and transport during the 2020-2021 pandemic (OR, 1.77, 95 % CI 1.08-2.90, p = 0.022). CONCLUSION: This study highlighted the difference between the characteristics in EMS for stroke and epileptic seizure by evaluating the response to cases with stroke-suspected seizure. Facilitating prompt and smooth transfers of such cases to an appropriate medical facility after admission could optimize the operation of specialized medical resources.

The long-term effects of heated tobacco product exposure on the central nervous system in a mouse model of prodromal Alzheimer's disease.

Heated tobacco products (HTPs) have emerged as novel alternatives to conventional cigarettes (CCs), marketed by the tobacco industry as having a reduced potential for harm. Nevertheless, a significant dearth of information remains regarding the long-term effects of HTPs on the central nervous system (CNS). Here, we sought to shed light on the repercussions of prolonged exposure to HTPs on the CNS, employing a mouse model mimicking prodromal Alzheimer's disease (AD). Our study entailed subjecting App knock-in mice to 16 weeks of HTP exposure, administered 5 days per week, with serum cotinine concentration serving as confirmation of HTP exposure within this model. Histological analysis, aimed at assessing amyloid pathology, unveiled a minimal impact attributable to HTPs. However, exploration of differentially expressed genes in the cerebral cortex, using unadjusted p values, indicated an association between HTP exposure and non-inflammatory pathways, specifically linked to neurohypophyseal and neuropeptide hormone activity within the CNS. Of note, similar results have already been observed after exposure to CCs in vivo. Our study not only contributes insights into the potential non-inflammatory effects of HTPs within the context of AD pathogenesis but also underscores the significance of continued research to comprehend the full scope of their impact on the CNS.

On-scene time delays for epileptic seizures in developed community-based integrated care system regions.

BACKGROUND: Delayed on-scene time by emergency medical services (EMS) can have detrimental effects on critical cases for people with epilepsy (PWE). In preparation for a super-aged society, a Community-based Integrated Care System is crucial to manage healthcare costs. However, sufficient coordination irrespective of sociomedical changes among medical providers is challenging. AIM: This study aimed to evaluate on-scene time delays in the treatment of PWE, identify factors associated with such delays, and clarify regional differences. The focus was on the volume of acute care beds in regions with a developed Community-based Integrated Care System. METHODS: This population-based observational study evaluated on-scene time delays in the treatment of PWE across six major cities in western Japan between 2017 and 2021. In addition, we also evaluated the association between regional differences focusing on volume of acute care beds ("Reduced region" and "Preserved region", as cities with numbers of acute care beds per 1,000 people below and above the national average, respectively) along with sociomedical factors associated with on-scene time delays. RESULTS: This study included 8,737 PWE transported by EMS, with a mean on-scene time for EMS ranging from 12.9 ± 6.8 min to 21.7 ± 10.6 min. On-scene time delays were evident in Reduced regions, with an increase of 1.45 min (95 % confidence interval 0.86-2.03 min, p < 0.001). A high total EMS call volume independently influenced on-scene time delays during the middle period of the pandemic in Reduced regions. CONCLUSION: Optimal coordination must be facilitated to ensure the effective functioning of the Community-based Integrated Care System, particularly during unusual circumstances.

Morphological study of the phrenic nerve to determine a reference value for the myelinated fiber density in elderly individuals.

Phrenic nerves (PNs) play an important role in respiration; however, very few morphological studies have assessed them. This study aimed to provide control reference values, including the density of large and small myelinated PN fibers, for future pathological studies. We assessed a total of nine nerves from eight cases among consecutive autopsy cases registered to the Brain Bank for Aging Research between 2018 and 2019 (five men and three women, mean age 77.0 ± 7.0 years). The nerves were sampled distally, and their structures were analyzed using semi-thin sections stained with toluidine blue. The mean and standard deviation of the density of each myelinated fiber of the PN was 6908 ± 1132 fibers/mm2 (total myelinated fiber), 4095 ± 586 fibers/mm2 (large diameter myelinated fiber; diameter ≥7 µm), and 2813 ± 629 fibers/mm2 (small diameter myelinated fiber; diameter <7 µm). There was no correlation between myelinated fiber density and age. This study provides the density measurement of the human PN myelinated fiber, and these findings can be used as reference values for the PN in elderly individuals.

On-scene time delays for epileptic seizures in emergencies during a social pandemic: A population-based study.

OBJECTIVES: The on-scene time of Emergency Medical Services (EMS), including time for hospital selection, is critical for people in an emergency. However, the outbreak of the novel coronavirus disease 2019 (COVID-19) led to longer delays in providing immediate care for individuals with non-COVID-19-related emergencies, such as epileptic seizures. This study aimed to examine factors associated with on-scene time delays for people with epilepsy (PWE) with seizures needing immediate amelioration. MATERIALS & METHODS: We conducted a population-based retrospective cohort study for PWE transported by EMS between 2016 and 2021. We used data from the Hiroshima City Fire Service Bureau database, divided into three study periods: "Pre period", the period before the COVID pandemic (2016-2019); "Early period", the early period of the COVID pandemic (2020); and "Middle period", the middle period of the COVID pandemic (2021). We performed linear regression modeling to identify factors associated with changes in EMS on-scene time for PWE during each period. In addition, we estimated the rate of total EMS call volume required to maintain the same on-scene time for PWE transported by EMS during the pandemic expansion. RESULTS: Among 2,205 PWE transported by EMS, significant differences in mean age and prevalence of impaired consciousness were found between pandemic periods. Total EMS call volume per month for all causes during the same month <5,000 (-0.55 min, 95% confidence interval [CI] -1.02 - -0.08, p = 0.022) and transport during the Early period (-1.88 min, 95%CI -2.75 - -1.00, p < 0.001) decreased on-scene time, whereas transport during the Middle period (1.58 min, 95%CI 0.70 - 2.46, p < 0.001) increased on-scene time for PWE transported by EMS. The rate of total EMS call volume was estimated as 0.81 (95%CI -0.04 - 1.07) during the expansion phase of the pandemic to maintain the same degree of on-scene time for PWE transported by EMS before the pandemic. CONCLUSIONS: On-scene time delays on PWE in critical care settings were observed during the Middle period. When the pandemic expanded, the EMS system required resource allocation to maintain EMS for time-sensitive illnesses such as epileptic seizures. Timely system changes are critical to meet dramatic social changes.

Bilateral tonic-clonic seizure and focal cortical hyperexcitability in familial Creutzfeldt-Jakob disease with E200K mutation of the prion protein.

Convulsive epileptic seizures are rare in Creutzfeldt-Jakob disease (CJD), and their clinical and EEG features have not been reported in detail. We describe a case of familial CJD with an E200K mutation of the prion protein who presented with bilateral tonic-clonic seizures (BTCS) during long-term video-EEG monitoring. Semiologically, BTCS showed focal clinical signs such as head turning and eye deviation to the left. The ictal EEG started with generalized polyspikes. Interictal EEG showed generalized periodic discharges with right fronto-temporal predominance (larger amplitude and earlier onset compared with other regions). MRI showed high-intensity signals persistently in the right temporo-parietal region on diffusion-weighted images (DWI). Interictal single-photon emission computed tomography (SPECT) showed hyperperfusion in the same region. Brain pathology revealed typical spongiform changes in CJD without other pathological findings of rapidly progressive dementia. Our case demonstrates that CJD can cause BTCS with generalized EEG changes and focal semiological/imaging abnormalities, suggesting that diffuse and inhomogeneous cortical and subcortical epileptic networks may develop in familial CJD.

Reversible Brain Atrophy in Cryptogenic New-onset Refractory Status Epilepticus.

Cryptogenic new-onset refractory status epilepticus (C-NORSE) is a neurologic emergency condition characterized by refractory status epilepticus (RSE) of unknown cause. Brain atrophy in a setting of C-NORSE is usually irreversible. A 33-year-old woman who was highly suspected of C-NORSE once showed mild frontotemporal atrophy on brain magnetic resonance imaging (MRI), but follow-up MRI revealed recovery of the brain atrophy. Her cognitive function also gradually improved, with a reduction in seizure frequency. Early initiation of intensive immunotherapy with anti-seizure medications may have minimized irreversible brain damage associated with RSE, resulting in a relatively good outcome.

Knockdown of optineurin controls C2C12 myoblast differentiation via regulating myogenin and MyoD expressions.

Mutations in optineurin (OPTN) have been identified in a small proportion of sporadic and familial amyotrophic lateral sclerosis (ALS) cases. Recent evidences suggest that OPTN would be involved in not only the pathophysiological mechanisms of motor neuron death of ALS but also myofiber degeneration of sporadic inclusion body myositis. However, the detailed role of OPTN in muscle remains unclear. Initially, we showed that OPTN expression levels were significantly increased in the denervated muscles of mice, suggesting that OPTN may be involved in muscle homeostasis. To reveal the molecular role of OPTN in muscle atrophy, we used cultured C2C12 myotubes treated with tumor necrosis factor-like inducer of apoptosis (TWEAK) as an in vitro model of muscle atrophy. Our data showed that OPTN had no effect on the process of muscle atrophy in this model. On the other hand, we found that myogenic differentiation was affected by OPTN. Immunoblotting analysis showed that OPTN protein levels gradually decreased during C2C12 differentiation. Furthermore, OPTN knockdown inhibited C2C12 differentiation, accompanied by reduction of mRNA and protein expression levels of myogenin and MyoD. These findings suggested that OPTN may have a novel function in muscle homeostasis and play a role in the pathogenesis of neuromuscular diseases.

An autopsied case of ADSSL1 myopathy.

ADSSL1 myopathy is an inherited myopathy with limb weakness, respiratory muscle paralysis, dysphagia, and myocardial symptoms. We present an autopsy case of a 66-year-old male carrying compound heterozygous variants c.781G>A (p.D261N) and c.919delA (p.I307fs) in ADSSL1. He had not run fast since school with no family history. He showed a gradual progression of limb weakness and developed dyspnoea, dysphagia, and Brugada syndrome at the age of 56. The magnetic resonance imaging (MRI) revealed bright tongue sign. Muscle biopsy showed only chronic myopathic changes. He died of respiratory muscle weakness at the age of 66. Autopsy revealed that there were many fibres with vacuoles and nemaline rods in the biceps brachii, tongue, diaphragm, and iliopsoas. Many lipopigments and nuclear clumps were also detected. The myocardium and central nervous system had only nonspecific age-related changes. This is the first autopsied case to clarify the terminal state of ADSSL1 myopathy.

Lewy pathology of the submandibular gland in Lewy body disease: A report of autopsy cases.

Accumulation of phosphorylated α-synuclein in the central and peripheral nervous systems is a histological hallmark of Lewy body disease (LBD), including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and LB-related pure autonomic failure. The submandibular gland is employed as a biopsy site for detecting Lewy pathology; however, the incidence of Lewy pathology in this region in autopsy-proven LBD cases at all stages from an aged Japanese cohort remains unclear. To validate the utility of Lewy pathology of the submandibular gland as a diagnostic biomarker for LBD, we investigated the submandibular gland Lewy pathology in autopsied patients. To determine the specificity, we prospectively evaluated the submandibular gland in 64 consecutive autopsied patients. To determine the sensitivity, we retrospectively assessed the submandibular gland in 168 consecutive autopsied patients who had prodromal or clinical LBD. In the prospective study, Lewy pathology was found in 21 of 64 patients, and nine of those 21 patients had the submandibular gland Lewy pathology. No Lewy pathology was found in 43 patients without CNS Lewy pathology, giving a specificity of 100%. In the retrospective study, Lewy pathology of the submandibular gland was detected in 126 of 168 patients. The sensitivity was 89.1% in PD and 75.4% in DLB. The sensitivity increased with disease progression. These findings support the utility of the submandibular gland biopsy for the pathological diagnosis of LBD.

Progression of phosphorylated α-synuclein in Macaca fuscata.

Prion-like spreading of abnormal proteins is proposed to occur in neurodegenerative diseases, and the progression of α-synuclein (α-syn) deposits has been reported in the brains of animal models injected with synthetic α-syn fibrils or pathological α-syn prepared from patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, α-syn transmission in nonhuman primates, which are more similar to humans, has not been fully clarified. Here, we injected synthetic human α-syn fibrils into the left striatum of a macaque monkey (Macaca fuscata). At 3 months after the injection, we examined neurodegeneration and α-syn pathology in the brain using α-syn epitope-specific antibodies, antiphosphorylated α-syn antibodies (pSyn#64 and pSer129), anti-ubiquitin antibodies, and anti-p62 antibodies. Immunohistochemical examination with pSyn#64, pSer129, and α-syn epitope-specific antibodies revealed Lewy bodies, massive α-syn-positive neuronal intracytoplasmic inclusions (NCIs), and neurites in the left putamen. These inclusions were also positive for ubiquitin and p62. LB509, a human-specific α-syn antibody targeting amino acid residues 115-122, showed limited immunoreactivity around the injection site. The left substantia nigra (SN) and the bilateral frontal cortex also contained some NCIs and neurites. The left hemisphere, including parietal/temporal cortex presented sparse α-syn pathology, and no immunoreactivity was seen in olfactory nerves, amygdala, hippocampus, or right parietal/temporal cortex. Neuronal loss and gliosis in regions with α-syn pathology were mild, except for the left striatum and SN. Our results indicate that abnormal α-syn fibrils propagate throughout the brain of M. fuscata via projection, association, and commissural fibers, though the progression of α-syn pathology is limited.

Lewy pathology of the esophagus correlates with the progression of Lewy body disease: a Japanese cohort study of autopsy cases.

Lewy body disease (LBD) is a spectrum of progressive neurodegenerative disorders characterized by the wide distribution of Lewy bodies and neurites in the central and peripheral nervous system (CNS, PNS). Clinical diagnoses include Parkinson's disease (PD), dementia with Lewy bodies, or pure autonomic failure. All types of LBD are accompanied by non-motor symptoms (NMSs) including gastrointestinal dysfunctions such as constipation. Its relationship to Lewy body-related α-synucleinopathy (Lewy pathology) of the enteric nervous system (ENS) is attracting attention because it can precede the motor symptoms. To clarify the role of ENS Lewy pathology in disease progression, we performed a clinicopathological study using the Brain Bank for Aging Research in Japan. Five-hundred and eighteen cases were enrolled in the study. Lewy pathology of the CNS and PNS, including the lower esophagus as a representative of the ENS, was examined via autopsy findings. Results showed that one-third of older people (178 cases, 34%) exhibited Lewy pathology, of which 78 cases (43.8%) exhibited the pathology in the esophagus. In the esophageal wall, Auerbach's plexus (41.6%) was most susceptible to the pathology, followed by the adventitia (33.1%) and Meissner's plexus (14.6%). Lewy pathology of the esophagus was significantly associated with autonomic failures such as constipation (p < 0.0001) and among PNS regions, correlated the most with LBD progression (r = 0.95, p < 0.05). These findings suggest that the propagation of esophageal Lewy pathology is a predictive factor of LBD.

[A case of hemichorea caused by right internal carotid artery stenosis].

This is a case of a 71 years old man. Hemichorea appeared in the left half of his body in the middle of November, 2014. Minute hyperintense areas in the white matter near the posterior horn of the right lateral ventricle and in the right parasagittal frontal cortex was shown in MRI diffusion weighted image. Severe stenosis was seen in the right internal carotid artery, and reduction in cerebral blood flow of the right cerebral hemisphere including the basal ganglia was shown in single photon emission computed tomography (SPECT). After having carotid endarterectomy of the right internal carotid artery in January, 2015, hemichorea disappeared, and the cerebral blood flow of the right cerebral hemisphere improved. It is known that hemichorea is caused by the infarction of the basal ganglia. In recent years, some hemichorea cases are reported around East Asia caused by internal carotid artery stenosis with reduction in cerebral blood flow.

Novel Asp511Thr mutation in McArdle disease with acute kidney injury caused by rhabdomyolysis.

McArdle disease (glycogen storage disease type V) is a rare hereditary metabolic myopathy. It can be overlooked clinically because it often presents as chronic asymptomatic hypercreatine phosphokinasemia (hyperCKemia). However, vigorous exercise or infections can trigger severe rhabdomyolysis. We present the case of a patient with long-term idiopathic hyperCKemia who, after contracting an upper respiratory tract infection, developed severe rhabdomyolysis and acute kidney injury. Upon hemodialysis, his renal function recovered and CK levels fell to below baseline, and maintenance therapy with vitamin B6 was also started. A molecular diagnosis of McArdle disease was subsequently made. Whole-exome sequencing revealed homozygous c1538delG (p.Asp511Thr fs*28) mutations in the PYGM gene, which was a novel mutation. Therefore, when investigating idiopathic hyperCKemia, glycogen storage disorders should also be considered.

[A case of MELAS with G13513A mutation presenting with chronic kidney disease long before stroke-like episodes].

The patient was a 35-year-old female with an 9-year history of chronic kidney disease awaiting renal transplantation. She was brought to hospital by ambulance due to a generalized convulsive seizure. Her consciousness remained disturbed after treatment for her seizure, and sensorineural deafness was noted. Lactic acid and pyruvic acid levels were extremely elevated in both the plasma and the cerebrospinal fluid, and brain atrophy was obvious on brain imaging. These findings suggested mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, which was confirmed by muscle biopsy. Previous renal biopsy specimen showed focal segmental glomerulosclerosis and granular swollen epithelial cells. She had no acute progression of the stroke-like episode with L-arginine treatment. However, the brain lesions expanded on MRI. Mitochondrial DNA analysis from a muscle biopsy specimen showed G13513A mutation. The G13513A mutation and the long history of preceding renal failure before the stroke-like episodes were distinctive features in this case.