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1.
Neurol Int ; 16(1): 95-112, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38251054

ABSTRACT

Traumatic brain injury (TBI) is a common diagnosis requiring acute hospitalization. Long-term, TBI is a significant source of health and socioeconomic impact in the United States and globally. The goal of clinicians who manage TBI is to prevent secondary brain injury. In this population, post-traumatic cerebral infarction (PTCI) acutely after TBI is an important but under-recognized complication that is associated with negative functional outcomes. In this comprehensive review, we describe the incidence and pathophysiology of PTCI. We then discuss the diagnostic and treatment approaches for the most common etiologies of isolated PTCI, including brain herniation syndromes, cervical artery dissection, venous thrombosis, and post-traumatic vasospasm. In addition to these mechanisms, hypercoagulability and microcirculatory failure can also exacerbate ischemia. We aim to highlight the importance of this condition and future clinical research needs with the goal of improving patient outcomes after TBI.

2.
Front Neurol ; 12: 714341, 2021.
Article in English | MEDLINE | ID: mdl-34887824

ABSTRACT

Introduction: Glycemic gap (GG), as determined by the difference between glucose and the hemoglobin A1c (HbA1c)-derived estimated average glucose (eAG), is associated with poor outcomes in various clinical settings. There is a paucity of data describing GG and outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Our main objectives were to evaluate the association of admission glycemic gap (aGG) with in-hospital mortality and with poor composite outcome and to compare aGG's predictive value to admission serum glucose. Secondary outcomes were the associations between aGG and neurologic complications including vasospasm and delayed cerebral ischemia following aSAH. Methods: We retrospectively reviewed 119 adult patients with aSAH admitted to a single tertiary care neuroscience ICU. Spearman method was used for correlation for non-normality of data. Area under the curve (AUC) for Receiver Operating Characteristic (ROC) curve was used to estimate prediction accuracy of aGG and admission glucose on outcome measures. Multivariable analyses were conducted to assess the value of aGG in predicting in-hospital poor composite outcome and death. Results: Elevated aGG at or above 30 mg/dL was identified in 79 (66.4%) of patients. Vasospasm was not associated with the elevated aGG. Admission GG correlated with admission serum glucose (r = 0.94, p < 0.01), lactate (r = 0.41, p < 0.01), procalcitonin (r = 0.38, p < 0.01), and Hunt and Hess score (r = 0.51, p < 0.01), but not with HbA1c (r = 0.02, p = 0.82). Compared to admission glucose, aGG had a statistically significantly improved accuracy in predicting inpatient mortality (AUC mean ± SEM: 0.77 ± 0.05 vs. 0.72 ± 0.06, p = 0.03) and trended toward statistically improved accuracy in predicting poor composite outcome (AUC: 0.69 ± 0.05 vs. 0.66 ± 0.05, p = 0.07). When controlling for aSAH severity, aGG was not independently associated with delayed cerebral ischemia, poor composite outcome, and in-hospital mortality. Conclusion: Admission GG was not independently associated with in-hospital mortality or poor outcome in a population of aSAH. An aGG ≥30 mg/dL was common in our population, and further study is needed to fully understand the clinical importance of this biomarker.

3.
Clin Neurol Neurosurg ; 208: 106871, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34391085

ABSTRACT

BACKGROUND: Intracerebral hemorrhage (ICH) is the most common type of hemorrhagic stroke. Glycemic gap, determined by the difference between glucose and the HbA1c-derived average glucose, predicts poor outcomes in various clinical settings. Our main objective was to evaluate association of some admission factors and outcomes in relation to admission glycemic gap (AGG) in patients with ICH. METHODS: We retrospectively analyzed 506 adult patients with ICH between 2014 and 2019. AGG was defined as A1c-derived average glucose (28.7×HbA1c-46.7) subtracted from admission glucose. Admission factors and hospital outcomes indicative of poor outcome (i.e. death, gastrostomy tube, tracheostomy, and discharge status) were compared between patients with elevated (greater than 80 mg/dL) vs. non-elevated (less than or equal-to 80 mg/dL) AGG. Pearson chi-square test was used for independence, and multivariate analysis was used for association. SPSS and excel were used for all data analysis. RESULTS: We found that 67 of 506 (13%) ICH patients had elevated AGG with a mean of 137.3 mg/dL compared to 439 (87%) non-elevated AGG with a mean of 12.6 mg/dL. While mean and standard deviation values for age, weight,and body mass index were comparable between groups, the elevated AGG group had significantly higher admission glucose (286.1 ± 84.3 vs. 140.1 ± 42.5, p < 0.001), higher lactic acid (3.26 ± 2.04 mmol/L vs. 1.99 ± 1.33 mmol/L, p < 0.001), lower Glasgow Coma Scale (GCS) scores (7.70 ± 4.28 vs. 11.24 ± 4.14, p < 0.001), and higher ICH score (median 3, IQR 2-4 vs. median 1, IQR 0-3, p < 0.001). Higher AGG was associated with an increased likelihood of mechanical ventilation, and in-hospital mortality (74.6% vs. 38.3% and 47.8% vs. 15.0% respectively, p < 0.001). Placements of tracheostomy and gastrostomy were similar between the two groups (13.4% vs. 11.8%, p = 0.69% and 1.5% and 4.6%, p = 0.34 respectively). The higher AGG group had a more common poor discharge outcome to either long-term acute care, skilled nursing facility, and/or hospice (65.7% vs. 42.6%, p < 0.001). Hospital cost and length of hospitalization did not differ significantly. Although AGG was not an independent predictor of poor outcome, multivariate analysis showed it was significantly associated with poor outcome while admission glucose was not (p < 0.001 vs. p = 0.167). CONCLUSION: Elevated AGG was associated with worse GCS and ICH scores on admission, as well as need for mechanical ventilation, in hospital mortality and poor discharge status. Elevated AGG has value in prediction of outcome, but existing understanding is limited.


Subject(s)
Blood Glucose/analysis , Cerebral Hemorrhage/diagnosis , Patient Admission , Aged , Cerebral Hemorrhage/blood , Cerebral Hemorrhage/mortality , Female , Glycated Hemoglobin/analysis , Hospital Mortality , Humans , Male , Patient Discharge , Prognosis , Retrospective Studies
4.
Pacing Clin Electrophysiol ; 44(4): 651-656, 2021 04.
Article in English | MEDLINE | ID: mdl-33592679

ABSTRACT

BACKGROUND: Pulmonary vein isolation (PVI) with autonomic modulation may be more successful than PVI alone for atrial fibrillation (AF) ablation and may be signaled by changes in sinus rhythm heart rate (HR) post ablation. We sought to determine if a change in sinus rhythm HR predicted AF recurrence post PVI. METHODS: Patients who underwent AF ablation from 2000 to 2011 were included if sinus rhythm was noted on ECG within 90 days pre and 7 days post ablation. Basic ECG interval and HR changes were analyzed and outcomes determined. RESULTS: A total of 1152 patients were identified (74.3% male, mean age 57 ± 11 years). Mean AF duration was 5.2 ± 5.3 years. Paroxysmal AF was noted in 712 (61.8%) of the patients. Mean EF was 61% ± 6%. Sinus rhythm HR was 61 ± 11 pre-ablation and 76 ± 13 bpm post-ablation (27% ± 24% increase, p < .001). The ability of relative HR change post-ablation to predict AF recurrence was borderline (hazard ratio 0.65 [0.41-1.01], p = .067). With patients separated into quartiles based on the relative HR change, the upper quartile with the largest relative increase in HR had a significantly lower rate of AF recurrence compared to the lowest quartile following multi variable modeling (p = .038). There were significant changes in PR (171 ± 28 to 167 ± 30 ms) and QTc (424 ± 25 to 434 ± 29 ms) intervals (both p < .001) but these were not predictive of outcome. CONCLUSION: Relative changes in HR post AF ablation correlates with AF recurrence. Further prospective studies are needed to confirm this relationship.


Subject(s)
Atrial Fibrillation/surgery , Catheter Ablation , Heart Rate/physiology , Pulmonary Veins/surgery , Adult , Atrial Fibrillation/physiopathology , Child , Female , Heart Atria/physiopathology , Humans , Infant , Male , Middle Aged , Recurrence
6.
Mayo Clin Proc Innov Qual Outcomes ; 4(2): 143-149, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32280924

ABSTRACT

OBJECTIVE: To assess familiarity with sarcoma guidelines among primary care practitioners (PCPs) in Minnesota. PARTICIPANTS AND METHODS: Surveys were distributed at 2 educational conferences held in Minnesota on April 16-17, 2015, and October 24, 2015. The PCPs were asked a series of questions about their current practice, past experience with sarcoma, and familiarity with sarcoma guidelines. They were then given a series of case presentations and asked to indicate if they would pursue a sarcoma work-up given the information provided. RESULTS: The study group included 80 physicians and 32 nurse practitioners (NPs). Over their careers (median, 14 years), physicians reported seeing a mean of 2.2 cases of soft tissue sarcoma and 0.7 cases of bone sarcoma. The NPs reported seeing a mean of 0.7 and 0.2 cases, respectfully, over their careers (median, 8 years). Both physicians and NPs reported low familiarity with sarcoma guidelines. When challenged with case presentations for which urgent referral to a sarcoma specialist is recommended, more than 50% of PCPs did not indicate that they would refer patients. The PCPs who had previous experience with soft tissue sarcoma and bone sarcoma estimated that only 17% and 23% of their patients, respectively, were diagnosed within 1 month of presentation. The most reported reason for a delayed diagnosis was the PCP advising the patient to "watch and wait." CONCLUSION: Minnesota PCPs have seen very few cases of sarcoma and report low familiarity with sarcoma guidelines. When challenged with case presentations, PCPs made decisions inconsistent with established guidelines. This study supports ongoing efforts to increase sarcoma awareness.

7.
Pediatr Surg Int ; 36(3): 341-355, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31938836

ABSTRACT

PURPOSE: The objective of this study was to examine the long-term outcomes of pediatric patients who underwent surgical resection for lipoblastoma and lipoblastomatosis (LB/LBM). METHODS: A single-center retrospective study of pediatric patients with LB/LBMs seen between 1991 and 2015 was conducted. A systematic review, including studies published prior to late August 2018, was performed. Using a random effect meta-analysis, pooled weighted proportions and unadjusted odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: The retrospective study included 16 patients, while the systematic review included 19 published studies consisting of 381 patients. Among 329 (82%) patients with follow-up information, the pooled recurrence rate was 16.8% (95% CI 10.9-23.5%; I2 = 59%). The reported time to recurrence ranged from < 1 to 8 years. Recurrence risk was greater for incomplete (n = 34) than complete resection (n = 150): OR 11.4 (95% CI 3.0-43.6; I2 = 43%). LBMs (n = 35) had a greater recurrence risk than LBs (n = 116): OR 5.5 (95% CI 1.9-15.9; I2 = 0%). Recurrences were higher for studies with approximately ≥ 3 years of follow-up versus studies with < 3 years of follow-up. CONCLUSION: Recurrences are more likely to occur with LBMs and/or incomplete resection. Follow-up beyond 3-5 years should be considered given that the recurrence risk appears to be greater in the long-term.


Subject(s)
Lipoblastoma/surgery , Soft Tissue Neoplasms/surgery , Surgical Procedures, Operative/methods , Child , Follow-Up Studies , Humans , Time Factors , Treatment Outcome
8.
J Drugs Dermatol ; 16(7): 711-713, 2017 Jul 01.
Article in English | MEDLINE | ID: mdl-28697227

ABSTRACT

Pyoderma gangrenosum (PG) is a neutrophilic, ulcerative dermatosis that can develop at sites of cutaneous trauma, including surgical incisions, a phenomenon known as pathergy. The characteristic lesion is a painful, rapidly expanding ulceration with a violaceous undermined border.1 A biopsy taken from the expanding violaceous border shows predominantly neutrophilic dermal inflammation with neutrophilic abscess formation.

The etiology of PG appears to be variable among patients, as about a half of the reported cases are associated with systemic disease such as inflammatory bowel disease, rheumatoid arthritis, or myeloproliferative disorders, while the other half seem to be idiopathic.2 PG is difficult to diagnose as other etiologies, including infectious, vasculitic, and other inflammatory dermatoses, must be excluded.1 Histopathologic and biochemical markers of PG, such as dermal neutrophilic infiltrate or overexpression of interleukin-8,3 respectively, are not pathognomonic. Given that several drugs, such as hydralazine, mesalamine, and sunitinib, are reportedly associated with PG, failure to recognize this association and stop these medications may delay diagnosis and therapy. We report a case of idiopathic postoperative PG following video-assisted thoracic surgery (VATS).

J Drugs Dermatol. 2017;16(7):711-713.

.


Subject(s)
Postoperative Complications/diagnosis , Postoperative Complications/etiology , Pyoderma Gangrenosum/diagnosis , Pyoderma Gangrenosum/etiology , Thoracic Surgery, Video-Assisted/adverse effects , Debridement/methods , Female , Humans , Middle Aged , Postoperative Complications/surgery , Pyoderma Gangrenosum/surgery , Thoracic Surgery, Video-Assisted/trends
9.
J Vasc Surg Venous Lymphat Disord ; 5(2): 185-193, 2017 03.
Article in English | MEDLINE | ID: mdl-28214485

ABSTRACT

OBJECTIVE: Peripheral venous reconstruction surgery may be necessary for appropriate oncologic resection; however, the operative approach and surgical outcomes are not well described. We report our experience with these complex reconstructions to identify best practice. METHODS: We retrospectively reviewed all adult patients who underwent peripheral vein reconstruction for tumor resection at Mayo Clinic, Rochester (2000-2015). Patients were classified into three subgroups by the location: iliac (IL), lower extremity (LE), and upper extremity (UE). Location, type of reconstruction, operative morbidity, as well as long-term patency, limb salvage, recurrence-free survival, and overall survival were recorded. RESULTS: We identified 27 patients (11 women and 16 men), with a mean age of 55 ± 15 years, who underwent 28 operations involving vein reconstruction during tumor resection. One patient underwent two vascular reconstructions for recurrent malignant fibrous histiocytoma. Concomitant artery reconstruction was required in 16 (57%). The most commonly treated tumors were rectal cancer (n = 4) and liposarcoma (n = 3). Reconstructions were IL in 19 (68%), LE in 6 (21%), and UE in 3 (11%). Venous reconstructions consisted of 7 vein grafts (25%), 17 polytetrafluoroethylene prosthetic grafts (61%), 1 cryograft (4%), and 3 isolated patch angioplasties (11%). Two additional patch angioplasty procedures were performed in conjunction with vein grafts (1 polytetrafluoroethylene, 1 vein graft). There were no 30-day deaths. The mean hospital length of stay was 13.5 ± 10.5 days. Medications prescribed at discharge were aspirin in 15 patients (54%) and warfarin in 16 (57%). Surgical complications included renal failure (n = 5), respiratory complication (n = 3), surgical site infection (n = 5), graft infection (n = 3), and lymph leak (n = 5). The median follow-up was 4.4 years (range, 17 days-14.1 years). At 2 and 5 years, overall primary patency was 61% (95% confidence interval [CI], 41%-87%) and 61% (95% CI, 36%-87%), respectively, and overall freedom from graft thrombosis was 87% (95% CI, 69%-100%) and 87% (95% CI, 64%-100%), respectively. Graft thrombosis occurred in five patients (18%; 4 IL, 1 LE), of which four were prosthetic and one was a patch site. These were managed by thrombolysis (n = 1), thrombectomy (n = 1), and medical management (n = 3). Two patients (7.1%) underwent ipsilateral amputation at 3 and 314 days for compartment syndrome and metastatic pain. The overall survival rate was 74% (95% CI, 50%-87%) at 2 years and 56% (95% CI, 32%-75%) at 5 years. Death was predominantly from cancer-associated morbidities. Overall recurrence-free survival was 75% (95% CI, 57%-97%) at 2 years and 56% (95% CI, 31%-92%) at 5 years. CONCLUSIONS: In selected patients fit for advanced tumor resection, reconstruction of IL and extremity veins is a safe and durable, with excellent limb salvage. Vein and prosthetic reconstructions both appear effective; however, infectious complications and graft thrombosis remain important complications when selecting a prosthetic conduit.


Subject(s)
Angioplasty/methods , Neoplasms/surgery , Veins/surgery , Angioplasty/adverse effects , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/methods , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Retrospective Studies
10.
Ophthalmology ; 124(2): 257-262, 2017 02.
Article in English | MEDLINE | ID: mdl-27871763

ABSTRACT

PURPOSE: To report the prevalence, type, and cause of diplopia in medically and surgically treated patients with glaucoma. DESIGN: Cohort study. PARTICIPANTS: A total of 195 adult patients with glaucoma treated in a glaucoma referral practice. METHODS: A total of 195 adult patients with glaucoma who had undergone surgical or medical management were prospectively enrolled. Forty-seven patients had undergone glaucoma drainage device (GDD) surgery (Baerveldt 350, Baerveldt 250 [Abbott Medical Optics, Abbott Park, IL], or Ahmed FP7 [New World Medical Inc, Rancho Cucamonga, CA]), 61 patients had undergone trabeculectomy, and 87 patients were medically treated. All patients completed the Diplopia Questionnaire to assess diplopia. We defined the presence of diplopia as "sometimes," "often," or "always" in distance straight ahead or reading positions on the Diplopia Questionnaire. A chart review was performed jointly by a strabismus specialist and a glaucoma subspecialist to characterize the type and cause of the diplopia. MAIN OUTCOME MEASURES: Frequency, type, and cause of diplopia. RESULTS: Diplopia was reported in 41 of 195 medically and surgically treated patients (21%) with glaucoma. Binocular diplopia due to the glaucoma procedure was present in 11 of 47 patients (23%) after GDD (95% confidence interval, 12-38), which was significantly greater than in patients after trabeculectomy (2/61 [3%]; 95% confidence interval, 0.4-11; P = 0.002). The most common type of strabismus associated with binocular diplopia due to glaucoma surgery was hypertropia (10/11 GDD cases, 2/2 trabeculectomy cases). Monocular diplopia was found in a similar proportion of medically treated, post-trabeculectomy, and post-GDD cases (4/87 [5%], 4/61 [7%], and 2/47 [4%], respectively). Binocular diplopia not due to surgery was found in similar proportions of GDD, trabeculectomy, and medically treated cases (3/47 [6%], 5/61 [8%], and 10/87 [11%], respectively). CONCLUSIONS: Diplopia may be under-recognized in medically and surgically treated patients with glaucoma, and standardization of ascertaining patient symptoms using the Diplopia Questionnaire may be useful in these patients. Diplopia was more commonly seen after GDD than trabeculectomy, typically a noncomitant restrictive hypertropia. The prevalence of monocular diplopia and binocular diplopia unrelated to glaucoma surgery was similar among medical and surgical groups. It is important to counsel patients on the higher occurrence of diplopia associated with GDD surgery.


Subject(s)
Diplopia/epidemiology , Glaucoma Drainage Implants/adverse effects , Glaucoma/surgery , Trabeculectomy/adverse effects , Adult , Aged , Aged, 80 and over , Diplopia/diagnosis , Diplopia/etiology , Female , Humans , Male , Middle Aged , Prevalence , Prospective Studies , Strabismus/diagnosis
11.
World J Surg ; 40(12): 2956-2963, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27384174

ABSTRACT

BACKGROUND: In patients with persistent (P-PHPT) or recurrent (R-PHPT) primary hyperparathyroidism, preoperative localization is important. Selective parathyroid hormone venous sampling (sPVS) is an invasive technique that can be used to regionalize and/or lateralize the source of PHPT when noninvasive imaging studies are nonlocalizing. The aim of the present study was to assess the role of sPVS in the preoperative evaluation of patients with P-PHPT or R-PHPT and negative, equivocal, or discordant noninvasive imaging localization. METHODS: After IRB-approval a retrospective review of all patients with P-PHPT or R-PHPT and nonlocalizing noninvasive imaging that underwent sPVS from 2000 to 2014 was performed. The location of the source of PHPT at sPVS was predicted by a parathyroid hormone (PTH) gradient and compared to the surgical, pathology, and biochemical follow-up data as the gold standard. Sensitivity and positive predictive value (PPV) were calculated. RESULTS: Of 30 patients who underwent sPVS, 12 patients did not undergo surgical exploration due to negative or non-localizing PTH gradient (n = 8) or opted for medical management (n = 4). Of the 18 patients who underwent surgical exploration, 17 (94 %) had a positive PTH gradient and pathologic parathyroid tissue identified at surgery. Sensitivity and PPV of sPVS were 93 and 77 %, respectively, for all surgical cases, 86 and 60.0 % for cervical cases (n = 11), and 100 and 100 % for mediastinal cases (n = 7). Sixteen patients (89 %) were surgically cured. CONCLUSIONS: In patients with P-PHPT or R-PHPT and nonlocalizing imaging studies, sPVS is a sensitive test for localizing the source of PHPT when a positive PTH gradient is present.


Subject(s)
Hyperparathyroidism, Primary/blood , Hyperparathyroidism, Primary/diagnostic imaging , Parathyroid Hormone/blood , Phlebotomy/methods , Adult , Aged , Female , Humans , Hyperparathyroidism, Primary/pathology , Hyperparathyroidism, Primary/surgery , Male , Mediastinum , Middle Aged , Neck , Parathyroidectomy , Preoperative Care , Recurrence , Retrospective Studies , Sensitivity and Specificity , Young Adult
12.
Pediatr Neurol ; 53(3): 207-10, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26302699

ABSTRACT

RATIONALE: One challenge for families whose children are undergoing presurgical evaluation for epilepsy surgery is the unpredictable length of hospitalization for video-electroencephalograph monitoring. The goal of this study was to retrospectively evaluate length of stay in children admitted for presurgical evaluation at a tertiary referral center. METHODS: Duration of stay for children with medically intractable epilepsy admitted for presurgical evaluation to the Pediatric Epilepsy Monitoring Unit at Mayo Clinic Rochester between 2010 and 2013 was evaluated retrospectively. RESULTS: Of 140 children, surgical candidacy was determined in 122 (87.1%) (72 candidates, 50 noncandidates). The mean length of stay was 4.0 ± 3.7 days and was not predicted by candidacy for surgery, age at monitoring, duration of epilepsy, number of antiepileptic drugs at admission, or focal/hemispheric magnetic resonance imaging abnormality. Shorter length of stay was predicted by younger age at epilepsy onset (P < 0.05) and shorter interval since most recent seizure (P = 0.001). Subtraction ictal single-photon emission computed tomography coregistered to magnetic resonance imaging was performed in 43 (35.2%) children, and correlated with longer length of stay (mean 5.1 ± 4.1 days for subtraction ictal single-photon emission computed tomography coregistered to magnetic resonance imaging users versus 3.5 ± 3.3 days for nonusers, P = 0.022). Antiepileptic drugs were reduced either upon or after admission in 67 (54.9%) children, and the length of stay was significantly longer in these patients (mean 5.5 ± 4.1 days if antiepileptic drugs were reduced versus 2.2 ± 2.1 days if not reduced, P < 0.001). CONCLUSIONS: Significant predictors of shorter length of stay include younger age at epilepsy onset, shorter interval from most recent seizure, lack of subtraction ictal single-photon emission computed tomography coregistered to magnetic resonance imaging, and lack of need for AED reduction on or after admission.


Subject(s)
Drug Resistant Epilepsy/diagnosis , Drug Resistant Epilepsy/therapy , Length of Stay , Age Factors , Anticonvulsants/therapeutic use , Brain/diagnostic imaging , Brain/pathology , Brain/physiopathology , Brain/surgery , Child , Drug Resistant Epilepsy/epidemiology , Electroencephalography/methods , Female , Humans , Linear Models , Magnetic Resonance Imaging , Male , Multivariate Analysis , Neurosurgical Procedures , Prognosis , Retrospective Studies , Tomography, Emission-Computed, Single-Photon , Video Recording/methods
14.
Elife ; 3: e03896, 2014 Nov 17.
Article in English | MEDLINE | ID: mdl-25402831

ABSTRACT

Long-term memory (LTM) is believed to be stored in the brain as changes in synaptic connections. Here, we show that LTM storage and synaptic change can be dissociated. Cocultures of Aplysia sensory and motor neurons were trained with spaced pulses of serotonin, which induces long-term facilitation. Serotonin (5HT) triggered growth of new presynaptic varicosities, a synaptic mechanism of long-term sensitization. Following 5HT training, two antimnemonic treatments-reconsolidation blockade and inhibition of PKM--caused the number of presynaptic varicosities to revert to the original, pretraining value. Surprisingly, the final synaptic structure was not achieved by targeted retraction of the 5HT-induced varicosities but, rather, by an apparently arbitrary retraction of both 5HT-induced and original synapses. In addition, we find evidence that the LTM for sensitization persists covertly after its apparent elimination by the same antimnemonic treatments that erase learning-related synaptic growth. These results challenge the idea that stable synapses store long-term memories.


Subject(s)
Aplysia/physiology , Behavior, Animal/physiology , Memory, Long-Term/physiology , Synapses/physiology , Animals , Aplysia/drug effects , Aplysia/enzymology , Behavior, Animal/drug effects , Benzophenanthridines/pharmacology , Coculture Techniques , Epigenesis, Genetic/drug effects , Histone Deacetylases/metabolism , Memory, Long-Term/drug effects , Microscopy, Confocal , Protein Kinase C/antagonists & inhibitors , Protein Kinase C/metabolism , Serotonin/pharmacology , Synapses/drug effects
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