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Journal of Neurology, Neurosurgery, and... Mar 2021To generate a score which clinically identifies surface-directed autoantibodies in adults with new-onset focal epilepsy, and evaluate the value of immunotherapy in this...
OBJECTIVE
To generate a score which clinically identifies surface-directed autoantibodies in adults with new-onset focal epilepsy, and evaluate the value of immunotherapy in this clinical setting.
METHODS
Prospective clinical and autoantibody evaluations in a cohort of 219 consecutive patients with new-onset focal epilepsy.
RESULTS
10.5% (23/219) of people with new-onset focal epilepsy had detectable serum autoantibodies to known or novel cell surface antigenic targets. 9/23 with autoantibodies were diagnosed with encephalitis, by contrast to 0/196 without autoantibodies (p<0.0001). Multivariate analysis identified six features which predicted autoantibody positivity (area under the curve=0.83): age ≥54 years, ictal piloerection, lowered self-reported mood, reduced attention, MRI limbic system changes and the absence of conventional epilepsy risk factors. 11/14 (79%) patients with detectable autoantibodies, but without encephalitis, showed excellent long-term outcomes (modified Rankin Score=0) despite no immunotherapy. These outcomes were superior to those of immunotherapy-treated patients with confirmed autoantibody-mediated encephalitis (p<0.05).
CONCLUSIONS
Seizure semiology, cognitive and mood phenotypes, alongside inflammatory investigation findings, aid the identification of surface autoantibodies among unselected people with new-onset focal epilepsy. The excellent immunotherapy-independent outcomes of autoantibody-positive patients without encephalitis suggests immunotherapy administration should be guided by clinical features of encephalitis, rather than autoantibody positivity. Our findings suggest that, in this cohort, immunotherapy-responsive seizure syndromes with autoantibodies largely fall under the umbrella of autoimmune encephalitis.
Topics: Adolescent; Adult; Aged; Autoantibodies; Cohort Studies; Encephalitis; Epilepsies, Partial; Female; Humans; Immunotherapy; Male; Middle Aged; Nerve Tissue Proteins; Predictive Value of Tests; ROC Curve; Young Adult
PubMed: 33219046
DOI: 10.1136/jnnp-2020-325011 -
Journal of the American Association For... Mar 2020Objectively recognizing postoperative pain in mice is challenging, making it difficult to determine an appropriate postoperative analgesic regimen. Adult male mice...
Objectively recognizing postoperative pain in mice is challenging, making it difficult to determine an appropriate postoperative analgesic regimen. Adult male mice produce ultrasonic vocalizations after exposure to adult female urine (FiUSV). To determine if FiUSV can be used as a indicator of postoperative pain, FiUSV produced by male C57BL/6J mice were assessed for 5 d before and after vasectomy or sham surgery with or without sustained-release buprenorphine. Postoperative pain was assessed by monitoring vocalization using an ultrasonic microphone and by evaluating orbital tightness, posture, and piloerection at postoperative time points. Before vasectomy or sham surgery, 25 of 38 male mice produced FiUSV on 4 of 5 d (143 ± 93 FiUSV). Vasectomized mice without postoperative analgesia produced significantly fewer FiUSV (59 ± 26 FiUSV) compared with baseline (212 ± 102 FiUSV) at 4 h postoperatively, but returned to baseline by 28 h. Vasectomized mice treated with buprenorphine and sham-surgery mice had no change in FiUSV from baseline at any time point after surgery. Activity was decreased compared with baseline in vasectomized mice, regardless of receiving postoperative analgesia or not, but only at the 4-h time point. There were no differences in behavior scores between vasectomized mice and sham-surgery mice at any time point. These results show that FiUSV can be used to detect postoperative pain in male C57BL/6J mice after vasectomy.
Topics: Analgesics, Opioid; Animals; Buprenorphine; Female; Humans; Male; Mice; Mice, Inbred C57BL; Pain Measurement; Pain, Postoperative; Postoperative Period; Ultrasonics; Vasectomy; Vocalization, Animal
PubMed: 31918790
DOI: 10.30802/AALAS-JAALAS-19-000059 -
PLoS Pathogens Dec 2021Kyasanur Forest disease virus (KFDV) and the closely related Alkhurma hemorrhagic disease virus (AHFV) are emerging flaviviruses that cause severe viral hemorrhagic...
Kyasanur Forest disease virus (KFDV) and the closely related Alkhurma hemorrhagic disease virus (AHFV) are emerging flaviviruses that cause severe viral hemorrhagic fevers in humans. Increasing geographical expansion and case numbers, particularly of KFDV in southwest India, class these viruses as a public health threat. Viral pathogenesis is not well understood and additional vaccines and antivirals are needed to effectively counter the impact of these viruses. However, current animal models of KFDV pathogenesis do not accurately reproduce viral tissue tropism or clinical outcomes observed in humans. Here, we show that pigtailed macaques (Macaca nemestrina) infected with KFDV or AHFV develop viremia that peaks 2 to 4 days following inoculation. Over the course of infection, animals developed lymphocytopenia, thrombocytopenia, and elevated liver enzymes. Infected animals exhibited hallmark signs of human disease characterized by a flushed appearance, piloerection, dehydration, loss of appetite, weakness, and hemorrhagic signs including epistaxis. Virus was commonly present in the gastrointestinal tract, consistent with human disease caused by KFDV and AHFV where gastrointestinal symptoms (hemorrhage, vomiting, diarrhea) are common. Importantly, RNAseq of whole blood revealed that KFDV downregulated gene expression of key clotting factors that was not observed during AHFV infection, consistent with increased severity of KFDV disease observed in this model. This work characterizes a nonhuman primate model for KFDV and AHFV that closely resembles human disease for further utilization in understanding host immunity and development of antiviral countermeasures.
Topics: Animals; Chlorocebus aethiops; Cytokines; Disease Models, Animal; Encephalitis Viruses, Tick-Borne; Encephalitis, Tick-Borne; Female; HEK293 Cells; Hemorrhagic Fevers, Viral; Humans; Lymph Nodes; Macaca nemestrina; Vero Cells; Viremia
PubMed: 34855915
DOI: 10.1371/journal.ppat.1009678 -
Nederlands Tijdschrift Voor Geneeskunde Sep 2021Depending on the level and severity of spinal cord injury (SCI), SCI patients may suffer from loss of autonomic nervous system function besides the well-known motor and...
Depending on the level and severity of spinal cord injury (SCI), SCI patients may suffer from loss of autonomic nervous system function besides the well-known motor and sensory function loss. Changes in the autonomic control of the cardiovascular system can lead to the life-threatening phenomenon of autonomic dysreflexia (AD), especially in patients with cervical or high thoracic SCI. AD is defined as a sudden increase in systolic blood pressure of at least 20 mmHg above baseline. It results from an uncontrolled reaction of the sympathetic nervous system to a stimulus below the neurological SCI level. The characteristic symptoms above the neurological level are caused by vasodilation (headache, flushing, sweating, nasal congestion) whereas the symptoms below the neurological level are caused by vasoconstriction (piloerection). Recognition and appropriate management of AD are essential in preventing life-threatening complications of hypertensive crisis as well as identifying underlying disease requiring further treatment.
Topics: Autonomic Dysreflexia; Autonomic Nervous System; Blood Pressure; Humans; Hypotension; Spinal Cord; Spinal Cord Injuries
PubMed: 34854619
DOI: No ID Found -
Scientific Reports Jan 2021Hair regenerative medicine has emerged as a promising approach for the treatment of severe hair loss. Recent advances in three-dimensional tissue engineering, such as...
Hair regenerative medicine has emerged as a promising approach for the treatment of severe hair loss. Recent advances in three-dimensional tissue engineering, such as formation of hair follicle germs (HFGs), have considerably improved hair regeneration after transplantation in animal models. Here, we proposed an approach for fabricating HFGs containing vascular endothelial cells. Epithelial, dermal papilla, and vascular endothelial cells initially formed a single aggregate, which subsequently became a dumbbell-shaped HFG, wherein the vascular endothelial cells localized in the region of dermal papilla cells. The HFGs containing vascular endothelial cells exhibited higher expression of hair morphogenesis-related genes in vitro, along with higher levels of hair shaft regeneration upon transplantation to the dorsal side of nude mice, than those without vascular endothelial cells. The generated hair follicles represented functional characteristics, such as piloerection, as well as morphological characteristics comparable to those of natural hair shafts. This approach may provide a promising strategy for fabricating tissue grafts with higher hair inductivity for hair regenerative medicine.
Topics: Alopecia; Animals; Cells, Cultured; Endothelium, Vascular; Female; Hair Follicle; Humans; Mice; Mice, Inbred ICR; Mice, Nude; Regeneration; Regenerative Medicine; Stem Cells; Tissue Engineering
PubMed: 33436760
DOI: 10.1038/s41598-020-79722-z -
Case Reports in Neurology 2021Autonomic status epilepticus (Aut SE) is a condition characterized by ongoing focal autonomic seizure lasting for >30 min. Aut SE can show a variety of clinical...
Autonomic status epilepticus (Aut SE) is a condition characterized by ongoing focal autonomic seizure lasting for >30 min. Aut SE can show a variety of clinical manifestations including vomiting, nausea, changes in heart rate, piloerection, pupillary abnormalities, and visual abnormalities. Although Aut SE is a common finding in childhood in the context of Panayiotopoulos syndrome, few reports have described this condition during adulthood. In the present report, we describe a case of Aut SE in an adult patient with parasellar meningioma and bilateral frontotemporal epileptiform activity on EEG record.
PubMed: 35111030
DOI: 10.1159/000519944 -
Epileptic Disorders : International... Oct 2021Musicogenic epilepsy (ME), a peculiar form of reflex epilepsy, represents a neurological rarity and yet another demonstration of the extraordinary power of music on the...
Musicogenic epilepsy (ME), a peculiar form of reflex epilepsy, represents a neurological rarity and yet another demonstration of the extraordinary power of music on the human brain. Despite the heterogeneity of the reported musical triggers, patients' emotional response to music is thought to play a crucial role in provoking seizures. Accordingly, the mesial temporal structures (especially of the non-dominant hemisphere) appear most involved in seizure generation, although a more complex fronto-temporal epileptogenic network was documented in some cases. Autoimmune encephalitis has been recently included among the many possible aetiologies of ME based on a few reports of music-induced seizures in patients with anti-glutamic acid decarboxylase 65 antibodies. Here, we describe the case of a 25-year-old man, educated in music over a long period of time, who had suffered from drug-resistant temporal lobe epilepsy following seronegative limbic encephalitis related to non-Hodgkin lymphoma. Along with spontaneous events, the patient also developed musicogenic seizures later in the disease course. After detecting five music-induced episodes via 24-hour ambulatory EEG, we performed prolonged video-EEG monitoring during which the patient presented a right temporal seizure (characterized by déjà-vu, piloerection and gustatory hallucinations) while listening to a hard rock song through headphones (which he had not previously heard). This observation allowed us to confirm the provoking effect of the music on our patient's seizures, despite the lack of any emotional drive, which suggests that a "cognitive" trigger was more likely in this case. Our report further highlights that autoimmune encephalitis should be investigated as a novel potential cause of musicogenic epilepsy, regardless of autoantibody status.
Topics: Adult; Drug Resistant Epilepsy; Electroencephalography; Epilepsy, Reflex; Humans; Limbic Encephalitis; Male; Music; Seizures
PubMed: 34612817
DOI: 10.1684/epd.2021.1322 -
The American Journal of Emergency... Feb 2020In a constantly increasing world of opioid addiction, naloxone has become a topic of great discussion and use. With seemingly minimal side effects, naloxone has become...
BACKGROUND
In a constantly increasing world of opioid addiction, naloxone has become a topic of great discussion and use. With seemingly minimal side effects, naloxone has become one of the most wellknown and widely used reversal agents for opioid intoxication. While more common effects of using naloxone include agitation, abdominal cramps, piloerection, diarrhea, nausea, and yawning, lesser known side effects involve muscle spasms, flushing, hyperreflexia in neonates, and seizures. This case study demonstrates a side effect of rigidity secondary to IV naloxone that has not previously been documented.
CASE
A 56 year old man was brought in by EMS after being found unresponsive in a car with a bag of drugs beside him. He was given 0.5 mg naloxone IV by EMS and immediately brought to the hospital. On arrival, the pt was noted to have tight rigidity of his upper extremities, with severe flexion. This presentation was not noted before the delivery of naloxone by EMS.
CONCLUSIONS
While this case highlights a patient with a rare side effect of naloxone, it reminds physicians that all medications come with a cost. Of course, ABCs remain the highest priority of resuscitation, however when administering a medication to reverse a drug overdose, it is important to keep in mind all possible consequences of said agent. Recognizing that complete muscle rigidity may remain a result of naloxone administration allows physicians to perhaps save patients from further medical workup.
Topics: Adult; Analgesics, Opioid; Emergency Service, Hospital; Female; Humans; Muscle Rigidity; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Syndrome; Thoracic Wall
PubMed: 31831344
DOI: 10.1016/j.ajem.2019.09.009 -
Developmental Psychobiology Sep 2020During infection, sickness behaviors, such as a hunched stance with piloerection, can facilitate host resistance by supporting the generation and maintenance of fever....
During infection, sickness behaviors, such as a hunched stance with piloerection, can facilitate host resistance by supporting the generation and maintenance of fever. Fever, in turn, is mediated by hypothalamic neuroimmune signaling. Sickness behaviors, however, can also be influenced by social stimuli. In this study, guinea pig pups were injected with lipopolysaccharide to simulate a bacterial infection and then exposed to a novel, threatening environment while either with their mother or alone. We found that the presence of the mother suppressed sickness behavior, but enhanced fever, and had no measureable effect on gene expression of hypothalamic mediators of fever. This 3-way dissociation induced by the mother's presence is interpreted in terms of the differential adaptive consequences of behavioral and febrile responses for pups in this situation. The results contribute to a growing literature linking immunological and social processes.
Topics: Animals; Behavior, Animal; Fear; Female; Fever; Gene Expression; Guinea Pigs; Hypothalamus; Illness Behavior; Lipopolysaccharides; Male; Mothers
PubMed: 32115686
DOI: 10.1002/dev.21962