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1.
Epilepsia ; 60(6): 1171-1183, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31112302

RESUMO

OBJECTIVE: Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) has reported seizure freedom rates between 36% and 78% with at least 1 year of follow-up. Unfortunately, the lack of robust methods capable of incorporating the inherent variability of patient anatomy, the variability of the ablated volumes, and clinical outcomes have limited three-dimensional quantitative analysis of surgical targeting and its impact on seizure outcomes. We therefore aimed to leverage a novel image-based methodology for normalizing surgical therapies across a large multicenter cohort to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE. METHODS: This multicenter, retrospective cohort study included 234 patients from 11 centers who underwent LITT for mTLE. To investigate therapy location, all ablation cavities were manually traced on postoperative magnetic resonance imaging (MRI), which were subsequently nonlinearly normalized to a common atlas space. The association of clinical variables and ablation location to seizure outcome was calculated using multivariate regression and Bayesian models, respectively. RESULTS: Ablations including more anterior, medial, and inferior temporal lobe structures, which involved greater amygdalar volume, were more likely to be associated with Engel class I outcomes. At both 1 and 2 years after LITT, 58.0% achieved Engel I outcomes. A history of bilateral tonic-clonic seizures decreased chances of Engel I outcome. Radiographic hippocampal sclerosis was not associated with seizure outcome. SIGNIFICANCE: LITT is a viable treatment for mTLE in patients who have been properly evaluated at a comprehensive epilepsy center. Consideration of surgical factors is imperative to the complete assessment of LITT. Based on our model, ablations must prioritize the amygdala and also include the hippocampal head, parahippocampal gyrus, and rhinal cortices to maximize chances of seizure freedom. Extending the ablation posteriorly has diminishing returns. Further work is necessary to refine this analysis and define the minimal zone of ablation necessary for seizure control.


Assuntos
Epilepsia do Lobo Temporal/cirurgia , Terapia a Laser/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tonsila do Cerebelo/diagnóstico por imagem , Criança , Estudos de Coortes , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia Tônico-Clônica/diagnóstico por imagem , Epilepsia Tônico-Clônica/cirurgia , Feminino , Humanos , Terapia a Laser/efeitos adversos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/cirurgia , Resultado do Tratamento , Adulto Jovem
2.
J Neurooncol ; 144(1): 193-203, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31240526

RESUMO

INTRODUCTION: Laser interstitial thermal therapy (LITT) is a novel MR thermometry-guided thermoablative tool revolutionizing the clinical management of brain tumors. A limitation of LITT is our inability to estimate a priori how tissues will respond to thermal energy, which hinders treatment planning and delivery. The aim of this study was to determine whether brain tumor LITT ablation dynamics may be predicted by features of the preoperative MRI and the relevance of these data, if any, to the recurrence of metastases after LITT. METHODS: Intraoperative thermal damage estimate (TDE) map pixels representative of irreversible damage were retrospectively quantified relative to ablation onset for 101 LITT procedures. Raw TDE pixel counts and TDE pixel counts modelled with first order dynamics were related to eleven independent variables derived from the preoperative MRI, demographics, laser settings, and tumor pathology. Stepwise regression analysis generated predictive models of LITT dynamics, and leave-one-out cross validation evaluated the accuracy of these models at predicting TDE pixel counts solely from the independent variables. Using a deformable atlas, TDE maps were co-registered to the immediate post-ablation MRI, allowing comparison of predicted and actual ablation sizes. RESULTS: Brain tumor TDE pixel counts modelled with first order dynamics, but not raw pixel counts, are correlated with the independent variables. Independent variables showing strong relations to the TDE pixel measures include T1 gadolinium and T2 signal, perfusion, and laser power. Associations with tissue histopathology are minimal. Leave-one-out analysis demonstrates that predictive models using these independent variables account for 77% of the variance observed in TDE pixel counts. Analysis of metastases treated revealed a trend towards the over-estimation of LITT effects by TDE maps during rapid ablations, which was associated with tumor recurrence. CONCLUSIONS: Features of the preoperative MRI are predictive of LITT ablation dynamics and could eventually be used to improve the clinical efficacy with which LITT is delivered to brain tumors.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Terapia a Laser/métodos , Imageamento por Ressonância Magnética/métodos , Modelos Teóricos , Cuidados Pré-Operatórios , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Valor Preditivo dos Testes , Estudos Retrospectivos
3.
Stereotact Funct Neurosurg ; 97(5-6): 347-355, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31935727

RESUMO

BACKGROUND: Laser interstitial thermal therapy (LITT) has recently gained popularity as a minimally invasive surgical option for the treatment of mesiotemporal epilepsy (mTLE). Similar to traditional open procedures for epilepsy, the most frequent neurological complications of LITT are visual deficits; however, a critical analysis of these injuries is lacking. OBJECTIVES: To evaluate the visual deficits that occur after LITT for mTLE and their etiology. METHOD: We surveyed five academic epilepsy centers that regularly perform LITT for cases of self-reported postoperative visual deficits. For these patients all pre-, intra- and postoperative MRIs were co-registered with an anatomic atlas derived from 7T MRI data. This was used to estimate thermal injury to early visual pathways and measure imaging variables relevant to the LITT procedure. Using logistic regression, we then compared 14 variables derived from demographics, mesiotemporal anatomy, and the surgical procedure for the patients with visual deficits to a normal cohort comprised of the first 30 patients to undergo this procedure at a single institution. RESULTS: Of 90 patients that underwent LITT for mTLE, 6 (6.7%) reported a postoperative visual deficit. These included 2 homonymous hemianopsias (HHs), 2 quadrantanopsias, and 2 cranial nerve (CN) IV palsies. These deficits localized to the posterior aspect of the ablation, corresponding to the hippocampal body and tail, and tended to have greater laser energy delivered in that region than the normal cohort. The patients with HH had insult localized to the lateral geniculate nucleus, which was -associated with young age and low choroidal fissure CSF volume. Quadrantanopsia, likely from injury to the optic radiation in Meyer's loop, was correlated with a lateral trajectory and excessive energy delivered at the tail end of the ablation. Patients with CN IV injury had extension of contrast to the tentorial edge associated with a mesial laser trajectory. CONCLUSIONS: LITT for epilepsy may be complicated by various classes of visual deficit, each with distinct etiology and clinical significance. It is our hope that by better understanding these injuries and their mechanisms we can eventually reduce their occurrence by identifying at-risk patients and trajectories and appropriately tailoring the ablation procedure.


Assuntos
Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/cirurgia , Terapia a Laser/efeitos adversos , Transtornos da Visão/diagnóstico por imagem , Transtornos da Visão/etiologia , Adulto , Criança , Estudos de Coortes , Feminino , Humanos , Terapia a Laser/métodos , Terapia a Laser/tendências , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/cirurgia
4.
Epilepsia ; 58(5): 801-810, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28244590

RESUMO

OBJECTIVE: To identify features of ablations and trajectories that correlate with optimal seizure control and minimize the risk of neurocognitive deficits in patients undergoing laser interstitial thermal therapy (LiTT) for mesiotemporal epilepsy (mTLE). METHODS: Clinical and radiographic data were reviewed from a prospectively maintained database of all patients undergoing LiTT for the treatment of mTLE at the University of Miami Hospital. Standard preoperative and postoperative evaluations, including contrast-enhanced magnetic resonance imaging (MRI) and neuropsychological testing, were performed in all patients. Laser trajectory and ablation volumes were computed both by manual tracing of mesiotemporal structures and by nonrigid registration of ablation cavities to a common reference system based on 7T MRI data. RESULTS: Among 23 patients with at least 1-year follow-up, 15 (65%) were free of disabling seizures since the time of their surgery. Sparing of the mesial hippocampal head was significantly correlated with persistent disabling seizures (p = 0.01). A lateral trajectory through the hippocampus showed a trend for poor seizure outcome (p = 0.08). A comparison of baseline and postoperative neurocognitive testing revealed areas of both improvement and worsening, which were not associated with ablation volume or trajectory. SIGNIFICANCE: At 1-year follow-up, LiTT appears to be a safe and effective tool for the treatment of mTLE, although a longer follow-up period is necessary to confirm these observations. Better understanding of the impact of ablation volume and location could potentially fine-tune this technique to improve seizure-freedom rates and associated neurologic and cognitive changes.


Assuntos
Lobectomia Temporal Anterior/métodos , Epilepsia do Lobo Temporal/cirurgia , Terapia a Laser/métodos , Transtornos Neurocognitivos/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Adulto , Tonsila do Cerebelo/cirurgia , Lobectomia Temporal Anterior/efeitos adversos , Mapeamento Encefálico , Epilepsia do Lobo Temporal/patologia , Feminino , Seguimentos , Hipocampo/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Fatores de Risco , Estatística como Assunto
5.
CNS Neurol Disord Drug Targets ; 20(3): 216-227, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-32951588

RESUMO

Traumatic Brain Injury (TBI) is still the worldwide leading cause of mortality and morbidity in young adults. Improved safety measures and advances in critical care have increased chances of surviving a TBI, however, numerous secondary mechanisms contribute to the injury in the weeks and months that follow TBI. The past 4 decades of research have addressed many of the metabolic impairments sufficient to mitigate mortality, however, an enduring secondary mechanism, i.e. neuroinflammation, has been intractable to current therapy. Neuroinflammation is particularly difficult to target with pharmacological agents due to lack of specificity, the blood brain barrier, and an incomplete understanding of the protective and pathologic influences of inflammation in TBI. Recent insights into TBI pathophysiology have established microglial activation as a hallmark of all types of TBI. The inflammatory response to injury is necessary and beneficial while the death of activated microglial is not. This review presents new insights on the therapeutic and maladaptive features of the immune response after TBI with an emphasis on microglial polarization, followed by a discussion of potential targets for pharmacologic and non-pharmacologic treatments. In aggregate, this review presents a rationale for guiding TBI inflammation towards neural repair and regeneration rather than secondary injury and degeneration, which we posit could improve outcomes and reduce lifelong disease burden in TBI survivors.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Microglia/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Animais , Barreira Hematoencefálica/metabolismo , Modelos Animais de Doenças , Humanos , Inflamação/tratamento farmacológico , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacos
6.
Neurosurgery ; 89(3): 496-503, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34156076

RESUMO

BACKGROUND: Laser interstitial thermal therapy (LITT) is a promising approach for cytoreduction of deep-seated gliomas. However, parameters contributing to treatment success remain unclear. OBJECTIVE: To identify extent of ablation (EOA) and time to chemotherapy (TTC) as predictors of improved overall and progression-free survival (OS, PFS) and suggest laser parameters to achieve optimal EOA. METHODS: Demographic, clinical, and survival data were collected retrospectively from 20 patients undergoing LITT for newly diagnosed glioblastoma (nGBM). EOA was calculated through magnetic resonance imaging-based volumetric analysis. Kaplan-Meier and multivariate Cox regression were used to examine the relationship between EOA with OS and PFS accounting for covariates (age, isocitrate dehydrogenase-1 (IDH1) mutation, O6-methylguanine-DNA methyltransferase hypermethylation). The effect of laser thermodynamic parameters (power, energy, time) on EOA was identified through linear regression. RESULTS: Median OS and PFS for the entire cohort were 36.2 and 3.5 mo respectively. Patient's with >70% EOA had significantly improved PFS compared to ≤70% EOA (5.2 vs 2.3 mo, P = .01) and trended toward improved OS (36.2 vs 11 mo, P = .07) on univariate and multivariate analysis. Total laser power was a significant predictor for increased EOA when accounting for preoperative lesion volume (P = .001). Chemotherapy within 16 d of surgery significantly predicted improved PFS compared to delaying chemotherapy (9.4 vs 3.1 mo, P = .009). CONCLUSION: Increased EOA was a predictor of improved PFS with evidence of a trend toward improved OS in LITT treatment of nGBM. A strategy favoring higher laser power during tumor ablation may achieve optimal EOA. Early transition to chemotherapy after LITT improves PFS.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Terapia a Laser , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/terapia , Estudos de Coortes , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Humanos , Lasers , Prognóstico , Estudos Retrospectivos
7.
World Neurosurg ; 136: e165-e170, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31874291

RESUMO

BACKGROUND: Microvascular decompression (MVD) is highly effective in managing the neuropathic facial pain of trigeminal neuralgia (TN). Its utility in patients with TN and concurrent multiple sclerosis (MS) has been a subject of debate. The goal of this study was to identify demographic and perioperative variables associated with favorable outcome after MVD over the past 20 years in patients from our institution. METHODS: A retrospective analysis of our cohort of 33 patients diagnosed with MS and TN who underwent MVD between 1997 and 2017 to treat neuropathic facial pain was performed. Perioperative variables included MS disease burden, findings on preoperative magnetic resonance imaging (MRI), TN pain severity, and the presence of intraoperative neurovascular compression. MS disease burden was quantified using the Expanded Disability Status Scale. Preoperative and postoperative pain severity was quantified using the Barrow Neurological Institute (BNI) pain severity scale. RESULTS: A total of 33 patients with TN and MS were treated with MVD at our institution (out of the 632 total MVDs performed) between 1997 and 2017. Twenty-two patients (67%) maintained a reduction in pain at a mean follow-up of 53.5 months. Higher preoperative BNI pain intensity score was associated with unfavorable outcome after MVD (P = 0.006). No associations were identified between MS disease burden, presence of neurovascular compression or pontine demyelinating plaques on MRI, or intraoperative findings of neurovascular compression and treatment outcomes. CONCLUSIONS: MVD is a reasonable treatment option for patients with TN and MS, although the rate of freedom from pain is lower than that for the general TN population. Preoperative pain severity may be a predictor of treatment success.


Assuntos
Cirurgia de Descompressão Microvascular/métodos , Esclerose Múltipla/complicações , Nervo Trigêmeo/diagnóstico por imagem , Neuralgia do Trigêmeo/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Neuralgia do Trigêmeo/complicações , Neuralgia do Trigêmeo/diagnóstico por imagem
8.
Oper Neurosurg (Hagerstown) ; 19(2): 195-204, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31828344

RESUMO

BACKGROUND: Prior treatment with magnetic resonance-guided, laser-induced thermal therapy (LITT) is widely assumed not to be a contraindication for further treatment of brain lesions, including further iterations of LITT. However, the safety and efficacy of repeat LITT treatments have never been formally investigated. OBJECTIVE: To evaluate treatment with multiple iterations of LITT. METHODS: All patients treated with LITT at least twice at our institution were included in the study. Outcomes and neurological examinations from before and after surgery were retrospectively examined from clinic notes. Perilesonal edema was determined at various timepoints using volumetric data derived from manual tracings of fluid-attenuated inversion recovery (FLAIR) enhancement on magnetic resonance imaging (MRI). Finally, a literature review of prior cases of repeat LITT was performed. RESULTS: A total of 9 patients underwent 18 treatments with LITT; all but 1 of whom were treated for metastatic brain lesions. One patient had a transient cerebrospinal fluid leak, whereas a second patient had a superficial wound infection, both of which resolved with standard medical care. The remaining 7 patients tolerated all LITT procedures without complication. Analysis of perilesional edema volume demonstrated a correlation with the amount of energy delivered during LITT. Literature review found 5 published papers describing 9 patients who underwent LITT more than once, the majority of whom tolerated repeat LITT well. CONCLUSION: LITT is a safe and promising treatment modality and may be used multiple times without issue. There appears to be an association between the amount of energy delivered during a LITT session and the degree of postoperative perilesional edema.


Assuntos
Neoplasias Encefálicas , Terapia a Laser , Cirurgiões , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Humanos , Lasers , Espectroscopia de Ressonância Magnética , Estudos Retrospectivos
9.
Neurol Clin Pract ; 10(4): 314-323, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32983611

RESUMO

OBJECTIVE: To provide a review of cognitive outcomes across a full neuropsychological profile in patients who underwent laser interstitial thermal therapy (LiTT) for mesiotemporal epilepsy (mTLE). METHODS: We examined cognitive outcomes following LiTT for mTLE by reviewing a consecutive series of 26 patients who underwent dominant or nondominant hemisphere procedures. Each patient's pre- and postsurgical performance was examined for clinically significant change (>1SD improvement or decline on standardized scores), with a neuropsychologic battery that included measures of language, memory, executive functioning, and processing speed. RESULTS: Presurgical performance was largely consistent with previous research, where patients suffering from dominant hemisphere epilepsies demonstrated deficits in verbal learning and memory, whereas patients with nondominant hemisphere scored lower on visually mediated tests. Case-by-case review comparing presurgical to postsurgical scores revealed clinically significant improvement in both dominant and nondominant patients in learning and memory and other aspects of cognition such as processing speed and executive functioning. Of the few patients who did experience clinically significant decline following LiTT, a greater proportion had undergone dominant hemisphere procedures. CONCLUSIONS: Compared with the outcome literature of dominant open anterior temporal lobectomies (ATLs), where postsurgical decline has been documented in up to 40%-60% of cases, our LiTT case series exhibited a much lower incidence of postoperative language or verbal memory decline. Moreover, promising rates of postoperative improvements were also observed across multiple cognitive domains. Future studies exploring cognitive outcomes following LiTT should include comprehensive neuropsychological findings, rather than only select domains, as clinically significant change can occur in areas other than those typically associated with mesiotemporal structures.

10.
Parkinsonism Relat Disord ; 70: 96-102, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31866156

RESUMO

INTRODUCTION: Deep brain stimulation (DBS) surgery is an efficacious, underutilized treatment for Parkinson's disease (PD). Studies of DBS post-operative outcomes are often restricted to data from a single center and consider DBS in isolation. National estimates of DBS readmission and post-operative outcomes are needed, as are comparisons to commonly performed surgeries. METHODS: This study used datasets from the 2013 and 2014 Nationwide Readmissions Database (NRD). Our sample was restricted to PD patients discharged alive after hospitalization for DBS surgery. Descriptive analyses examined patient, clinical, hospital and index hospitalization characteristics. The all-cause, non-elective 30-day readmission rate after DBS was calculated, and logistic regression models were built to examine factors associated with readmission. Readmission rates for the most common surgical procedures were calculated and compared to DBS. RESULTS: There were 6058 DBS surgeries for PD in our sample, most often involving a male aged 65 and older, who lived in a high socioeconomic status zip code. DBS patients had an average of four comorbidities. With respect to outcomes, the majority of patients were discharged home (95.3%). Non-elective readmission was rare (4.9%), and was associated with socioeconomic status, comorbidity burden, and teaching hospital status. Much higher acute, non-elective readmission rates were observed for common procedures such as upper gastrointestinal endoscopy (16.2%), colonoscopy (14.0%), and cardiac defibrillator and pacemaker procedures (11.1%). CONCLUSION: Short-term hospitalization outcomes after DBS are generally favorable. Socioeconomic disparities in DBS use persist. Additional efforts may be needed to improve provider referrals for and patient access to DBS.


Assuntos
Estimulação Encefálica Profunda/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Doença de Parkinson/epidemiologia , Doença de Parkinson/terapia , Readmissão do Paciente/estatística & dados numéricos , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Bases de Dados Factuais , Estimulação Encefálica Profunda/efeitos adversos , Feminino , Disparidades em Assistência à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Classe Social , Estados Unidos/epidemiologia
11.
Cereb Cortex ; 18(8): 1828-42, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18056699

RESUMO

Several studies have shown that neurons with similar response properties are arranged together in domains across primary visual cortex (V1). An orderly pattern of domains has been described for preferences to ocular dominance, orientation, and spatial frequency. Temporal frequency preference, another important attribute of the visual scene, also might be expected to map into different domains. Using optical imaging and a variety of quantitative methods, we examined how temporal frequency selectivity is mapped in V1 of the prosimian primate, bush baby (Otolemur garnetti). We found that unlike other attribute maps, selectivity for different temporal frequencies is arranged uniformly across V1 with no evidence of local clustering. Global tuning for temporal frequency, based on magnitude of response, showed a good match to previous tuning curves for single neurons. A peak response was found around 2.0 Hz, with smaller attenuation at lower temporal frequencies than at higher frequencies. We also examined whether the peak temporal frequency response differed between anatomical compartments defined by cytochrome oxidase (CO). No significant differences in the preference for temporal frequency were found between these CO compartments. Our findings show that key sensory attributes that are linked in perception can be organized in quite distinct ways in V1 of primates.


Assuntos
Mapeamento Encefálico/métodos , Galago/fisiologia , Córtex Visual/fisiologia , Animais , Feminino , Masculino , Fatores de Tempo , Vias Visuais/fisiologia
12.
Front Cell Neurosci ; 13: 510, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803022

RESUMO

The spinal cord after injury shows altered transcription in numerous genes. We tested in a pilot study whether the nucleus raphé magnus, a descending serotonergic brainstem region whose stimulation improves recovery after incomplete spinal cord injury (SCI), can influence these transcriptional changes. Rats received 2 h of low-frequency electrical stimulation in the raphé magnus 3 days after an impact contusion at segment T8. Comparison groups lacked injuries or activated stimulators or both. Immediately following stimulation, spinal cords were extracted, their RNA transcriptome sequenced, and differential gene expression quantified. Confirming many previous studies, injury primarily increased inflammatory and immune transcripts and decreased those related to lipid and cholesterol synthesis and neuronal signaling. Stimulation plus injury, contrasted with injury alone, caused significant changes in 43 transcripts (39 increases, 4 decreases), all protein-coding. Injury itself decreased only four of these 43 transcripts, all reversed by stimulation, and increased none of them. The non-specific 5-HT7 receptor antagonist pimozide reversed 25 of the 43 changes. Stimulation in intact rats principally caused decreases in transcripts related to oxidative phosphorylation, none of which were altered by stimulation in injury. Gene ontology (biological process) annotations comparing stimulation with either no stimulation or pimozide treatment in injured rats highlighted defense responses to lipopolysaccharides and microorganisms, and also erythrocyte development and oxygen transport (possibly yielding cellular oxidant detoxification). Connectivity maps of human orthologous genes generated in the CLUE database of perturbagen-response transcriptional signatures showed that drug classes whose effects in injured rats most closely resembled stimulation without pimozide include peroxisome proliferator-activated receptor agonists and angiotensin receptor blockers, which are reportedly beneficial in SCI. Thus the initial transcriptional response of the injured spinal cord to raphé magnus stimulation is upregulation of genes that in various ways are mostly protective, some probably located in recently arrived myeloid cells.

13.
Brain Sci ; 9(6)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31142050

RESUMO

Spinal cord injury (SCI) is a major cause of disability and pain, but little progress has been made in its clinical management. Low-frequency electrical stimulation (LFS) of various anti-nociceptive targets improves outcomes after SCI, including motor recovery and mechanical allodynia. However, the mechanisms of these beneficial effects are incompletely delineated and probably multiple. Our aim was to explore near-term effects of LFS in the hindbrain's nucleus raphe magnus (NRM) on cellular proliferation in a rat SCI model. Starting 24 h after incomplete contusional SCI at C5, intermittent LFS at 8 Hz was delivered wirelessly to NRM. Controls were given inactive stimulators. At 48 h, 5-bromodeoxyuridine (BrdU) was administered and, at 72 h, spinal cords were extracted and immunostained for various immune and neuroglial progenitor markers and BrdU at the level of the lesion and proximally and distally. LFS altered cell marker counts predominantly at the dorsal injury site. BrdU cell counts were decreased. Individually and in combination with BrdU, there were reductions in CD68 (monocytes) and Sox2 (immature neural precursors) and increases in Blbp (radial glia) expression. CD68-positive cells showed increased co-staining with iNOS. No differences in the expression of GFAP (glia) and NG2 (oligodendrocytes) or in GFAP cell morphology were found. In conclusion, our work shows that LFS of NRM in subacute SCI influences the proliferation of cell types implicated in inflammation and repair, thus providing mechanistic insight into deep brain stimulation as a neuromodulatory treatment for this devastating pathology.

14.
Brain Res Rev ; 55(2): 264-84, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17692925

RESUMO

At the time of Golgi and Cajal's reception of the Nobel Prize in 1906 most scientists had accepted the notion that neurons are independent units. Although neuroscientists today still believe that neurons are independent anatomical units, functionally, it is thought that some sort of population coding occurs. Throughout this essay, we provide evidence that suggests that populations of neurons can code information through the synchronization of their responses. This synchronization occurs at several levels in the brain. Whereas spike synchrony refers to the correlation between spikes of different neurons' spike trains, oscillatory synchrony refers to the synchronization of oscillatory responses, generally among large groups of neurons. In the first section of this essay we describe the dependence of the brain's developmental processes on synchronous firing and how these processes form a brain that supports and is sensitive to synchronous spikes. Data are then presented that suggest that spike and oscillatory synchrony may serve as useful neural codes. Examples from sensory (auditory, olfactory and somatosensory), motor and higher cognitive (attention, memory) systems are then presented to illustrate potential roles for these synchronous codes in normal brain function. Results from these studies collectively suggest that spike synchrony in sensory and motor systems may provide detail information not available from changes in firing rate. Oscillatory synchrony, on the other hand, may be globally involved in the coordination of long-distance neuronal communication during higher cognitive processes. These concepts represent a dramatic shift in direction since the times of Golgi and Cajal.


Assuntos
Rede Nervosa/fisiologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Animais , Modelos Neurológicos , Oscilometria
15.
PLoS One ; 13(7): e0199190, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29979717

RESUMO

INTRODUCTION: The recent emergence of laser interstitial thermal therapy (LITT) as a frontline surgical tool in the management of brain tumors and epilepsy is a result of advances in MRI thermal imaging. A limitation to further improving LITT is the diversity of brain tissue thermoablative properties, which hinders our ability to predict LITT treatment-related effects. Utilizing the mesiotemporal lobe as a consistent anatomic model system, the goal of this study was to use intraoperative thermal damage estimate (TDE) maps to study short- and long-term effects of LITT and to identify preoperative variables that could be helpful in predicting tissue responses to thermal energy. METHODS: For 30 patients with mesiotemporal epilepsy treated with LITT at a single institution, intraoperative TDE maps and pre-, intra- and post-operative MRIs were co-registered in a common reference space using a deformable atlas. The spatial overlap of TDE maps with manually-traced immediate (post-ablation) and delayed (6-month) ablation zones was measured using the dice similarity coefficient (DSC). Then, motivated by simple heat-transfer models, ablation dynamics were quantified at amygdala and hippocampal head from TDE pixel time series fit by first order linear dynamics, permitting analysis of the thermal time constant (τ). The relationships of these measures to 16 independent variables derived from patient demographics, mesiotemporal anatomy, preoperative imaging characteristics and the surgical procedure were examined. RESULTS: TDE maps closely overlapped immediate ablation borders but were significantly larger than the ablation cavities seen on delayed imaging, particularly at the amygdala and hippocampal head. The TDEs more accurately predicted delayed LITT effects in patients with smaller perihippocampal CSF spaces. Analyses of ablation dynamics from intraoperative TDE videos showed variable patterns of lesion progression after laser activation. Ablations tended to be slower for targets with increased preoperative T2 MRI signal and in close proximity to large, surrounding CSF spaces. In addition, greater laser energy was required to ablate mesial versus lateral mesiotemporal structures, an effect associated with laser trajectory and target contrast-enhanced T1 MRI signal. CONCLUSIONS: Patient-specific variations in mesiotemporal anatomy and pathology may influence the thermal coagulation of these tissues. We speculate that by incorporating demographic and imaging data into predictive models we may eventually enhance the accuracy and precision with which LITT is delivered, improving outcomes and accelerating adoption of this novel tool.


Assuntos
Epilepsia do Lobo Temporal/diagnóstico por imagem , Terapia a Laser/efeitos adversos , Lasers/efeitos adversos , Lobo Temporal/diagnóstico por imagem , Adulto , Idoso , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiopatologia , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/cirurgia , Feminino , Gadolínio/administração & dosagem , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Lobo Temporal/fisiopatologia , Lobo Temporal/cirurgia
16.
Seizure ; 61: 89-93, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30118930

RESUMO

PURPOSE: Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MRgLITT) is an emerging minimally-invasive alternative to resective surgery for medically-intractable epilepsy. The precise lesioning effect produced by MRgLITT supplies opportunities to glean insights into epileptogenic regions and their interactions with functional brain networks. In this exploratory analysis, we sought to characterize associations between MRgLITT ablation zones and large-scale brain networks that portended seizure outcome using resting-state fMRI. METHODS: Presurgical fMRI and intraoperatively volumetric structural imaging were obtained, from which the ablation volume was segmented. The network properties of the ablation volume within the brain's large-scale brain networks were characterized using graph theory and compared between children who were and were not rendered seizure-free. RESULTS: Of the seventeen included children, five achieved seizure freedom following MRgLITT. Greater functional connectivity of the ablation volume to canonical resting-state networks was associated with seizure-freedom (p < 0.05, FDR-corrected). The ablated volume in children who subsequently became seizure-free following MRgLITT had significantly greater strength, and eigenvector centrality within the large-scale brain network. CONCLUSIONS: These findings provide novel insights into the interaction between epileptogenic cortex and large-scale brain networks. The association between ablation volume and resting-state networks may supply novel avenues for presurgical planning and patient stratification.


Assuntos
Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Terapia a Laser/métodos , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Adolescente , Criança , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Monitorização Intraoperatória , Vias Neurais/cirurgia , Procedimentos Neurocirúrgicos , Descanso , Resultado do Tratamento , Adulto Jovem
17.
World Neurosurg ; 100: 74-84, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28034811

RESUMO

BACKGROUND: Spinal cord stimulation (SCS) is an efficacious treatment for various chronic pain syndromes culminating predominantly into spinal nerves. To improve intraoperative electrode placement, several groups have advocated the use of intraoperative neuromonitoring for localization of the spinal cord midline. In our study we present the case series of patients undergoing stimulator placement with consistent electromyographic intraoperative testing, with an emphasis on examining reoperation rates and complications. METHODS: After approval from the institutional review board, we retrospectively collected data on standard demographics, preoperative diagnoses, prior spine surgeries, electrode manufacturer, blood loss, complications, and patient outcome. RESULTS: The study included 103 patients with an average age of 60.7 years. Of these, 72 (69.9%) had prior spine surgery, which was associated with higher rate of reoperation (P = 0.019). The mean latency between initial SCS implantation and revision surgery ± SD was 14.6 ± 17.2 months, with a median time of 280 days. There was a 13.6% complication rate. Common complications that lead to reoperation included migrated electrode or failed generator. CONCLUSIONS: Our retrospective chart review of 103 patients indicates that patients receiving SCS implantation in conjunction with electromyographic monitoring have low complication rates and rarely return to the operating room for electrode repositioning or removal.


Assuntos
Eletromiografia , Neuroestimuladores Implantáveis , Monitorização Neurofisiológica Intraoperatória , Procedimentos Neurocirúrgicos , Estimulação da Medula Espinal , Medula Espinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Dor Crônica/epidemiologia , Dor Crônica/cirurgia , Eletromiografia/métodos , Falha de Equipamento , Feminino , Fluoroscopia , Humanos , Monitorização Neurofisiológica Intraoperatória/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos
18.
J Med Case Rep ; 11(1): 103, 2017 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-28407815

RESUMO

BACKGROUND: Symptomatic peri-lead edema is a rare complication of deep brain stimulation that has been reported to develop 4 to 120 days postoperatively. CASE PRESENTATION: Here we report the case of a 63-year-old Hispanic man with an 8-year history of Parkinson's disease who underwent bilateral placement of subthalamic nucleus deep brain stimulation leads and presented with acute, symptomatic, unilateral, peri-lead edema just 33 hours after surgery. CONCLUSIONS: We document a thorough radiographic time course showing the evolution of these peri-lead changes and their regression with steroid therapy, and discuss the therapeutic implications of these findings. We propose that the unilateral peri-lead edema after bilateral deep brain stimulation is the result of severe microtrauma with blood-brain barrier disruption. Knowledge of such early manifestation of peri-lead edema after deep brain stimulation is critical for ruling out stroke and infection and preventing unnecessary diagnostic testing or hardware removal in this rare patient population.


Assuntos
Edema Encefálico/diagnóstico por imagem , Estimulação Encefálica Profunda/efeitos adversos , Cefaleia/etiologia , Doença de Parkinson/terapia , Complicações Pós-Operatórias/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Anti-Inflamatórios/uso terapêutico , Edema Encefálico/terapia , Dexametasona/uso terapêutico , Cefaleia/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Ondansetron/uso terapêutico , Doença de Parkinson/fisiopatologia , Complicações Pós-Operatórias/terapia , Náusea e Vômito Pós-Operatórios , Núcleo Subtalâmico , Resultado do Tratamento , Conduta Expectante
19.
J Neurosurg Pediatr ; 20(2): 158-163, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28524790

RESUMO

Cognard Type V dural arteriovenous fistulas (dAVFs) are a unique type of cranial vascular malformation characterized by congestion of the perimedullary venous system that may lead to devastating spinal cord pathology if left untreated. The authors present the first known case of a pediatric patient diagnosed with a Type V dAVF. A 14-year-old girl presented with a 3-week history of slowly progressive unilateral leg weakness that quickly progressed to bilateral leg paralysis, sphincter dysfunction, and complete sensory loss the day of her presentation. MRI revealed an extensive T2 signal change in the cervical spine and tortuous perimedullary veins along the entire length of the cord. An emergency cranial angiogram showed a Type V dAVF fed by the posterior meningeal artery with drainage into the perimedullary veins of the cervical spine. The fistula was not amenable to embolization because vascular access was difficult; therefore, the patient underwent urgent suboccipital craniotomy and ligation of the arterialized venous drainage from the fistula. The patient's clinical course immediately reversed; she had a complete recovery over the course of a year, and she remains asymptomatic at the 2-year follow-up. This report adds to a growing body of evidence that describes the diverse and unpredictable nature of Type V dAVFs and highlights the need to obtain a cranial angiogram in pediatric patients with unexplained myelopathy and cervical cord T2 signal change on MRI.


Assuntos
Malformações Vasculares do Sistema Nervoso Central/complicações , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Doenças da Medula Espinal/etiologia , Doenças da Medula Espinal/cirurgia , Adolescente , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/reabilitação , Craniotomia , Progressão da Doença , Feminino , Humanos , Ligadura , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/reabilitação
20.
Oper Neurosurg (Hagerstown) ; 13(5): 627-633, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28922876

RESUMO

BACKGROUND: Laser interstitial thermal therapy (LITT) is quickly emerging as an effective surgical therapy for temporal lobe epilepsy (TLE). One of the most frequent complications of the procedure is postoperative visual field cuts, but the physiopathology of these deficits is unknown. OBJECTIVE: To evaluate potential causes of visual deficits after LITT for TLE in an attempt to minimize this complication. METHODS: This retrospective chart review compares the case of a 24-year-old male who developed homonymous hemianopsia following LITT for TLE to 17 prior patients who underwent the procedure and suffered no visual deficit. We examined both features of the surgical approach (trajectory, laser energy, ablation size) and of preoperative surgical anatomy, derived from volumetric tracings of mesiotemporal structures. RESULTS: For the patient with postoperative homonymous hemianopsia imaging suggested inadvertent ablation of the lateral geniculate nucleus, although the laser was positioned entirely within the hippocampus. This patient's laser trajectory, ablation number, energy delivered, and ablation size were not significantly different from the prior patients. However, the subject with the visual deficit did have significantly smaller choroidal fissure cerebrospinal fluid volume. CONCLUSION: Visual deficits are the most common complication of LITT for mesiotemporal epilepsy and patients at most risk may have small cerebrospinal fluid volume in the choroidal fissure, allowing heat to spread from the hippocampal body to the lateral geniculate nucleus. When such anatomy is identified on preoperative magnetic resonance imaging, we recommend lowering laser trajectory, decreasing ablation power through the hippocampal body, and using temperature safety markers at the lower thalamic border.


Assuntos
Epilepsia do Lobo Temporal/terapia , Hemianopsia/etiologia , Terapia a Laser/efeitos adversos , Imagem de Difusão por Ressonância Magnética , Epilepsia do Lobo Temporal/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Estudos Retrospectivos , Campos Visuais/fisiologia , Adulto Jovem
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