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1.
Stereotact Funct Neurosurg ; 99(1): 34-37, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32937628

RESUMO

Magnetic resonance imaging-guided focused ultrasound (MRgFUS) is a novel method for stereotactic brain lesioning and has primarily been applied for thalamotomies to treat essential tremor (ET). The electrophysiological properties of previously MRgFUS-sonicated thalamic neurons have not yet been described. We report on an ET patient who underwent an MRgFUS thalamotomy but experienced tremor recurrence. We expanded the MRgFUS-induced thalamic cavity using radiofrequency (RF), with good effect on the tremor but transient sensorimotor deficits and permanent ataxia. This is the first report of a patient undergoing RF thalamotomy after an unsuccessful MRgFUS thalamotomy. As we used microelectrode recording to guide the RF thalamotomy, we could also study for the first time the electrophysiological properties of previously sonicated thalamic neurons bordering the MRgFUS-induced cavity. These neurons displayed electrophysiological characteristics identical to those recorded from nonsonicated thalamic cells in ET patients. Hence, our findings support the widespread assumption that sonication below the necrotic threshold does not permanently alter neuronal function.


Assuntos
Tremor Essencial/diagnóstico por imagem , Tremor Essencial/terapia , Ablação por Radiofrequência/métodos , Tálamo/diagnóstico por imagem , Tálamo/cirurgia , Terapia por Ultrassom/métodos , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Microeletrodos , Psicocirurgia/métodos
2.
J Neurophysiol ; 122(4): 1367-1372, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31411948

RESUMO

Tremor is a well-known side effect from many psychiatric medications, including lithium and dopamine antagonists. In patients whose psychiatric symptoms are stabilized and only respond to certain medications, deep brain stimulation may offer relief of the consequent motor complications. We report the case of an elderly male with disabling tremor related to lithium therapy for bipolar affective disorder, who was subsequently treated with deep brain stimulation. In this patient, we obtained recordings from the substantia nigra pars reticulata and performed a high-frequency stimulation protocol that robustly elicits long-term potentiation (LTP)-like changes in patients with Parkinson's disease. We hypothesized that in this patient, who did not have Parkinson's disease, the levels of inhibitory plasticity would be much greater. However, we found an unanticipated lack of plasticity in the patient with lithium-induced tremor, compared with two de novo control patients with Parkinson's disease. This patient was successfully treated with deep brain stimulation in the vicinity of the ventral oral posterior nucleus, an area of the thalamus that receives inputs from the basal ganglia. We postulate that the lithium-induced blockade of LTP may bring about motor complications such as tremor while simultaneously contributing to the therapeutic mechanism for treating the symptoms of psychiatric disorders such as bipolar affective disorder.NEW & NOTEWORTHY Use of a dual-microelectrode technique enabled us to compare long-term potentiation (LTP)-like changes in a patient with lithium-induced tremor to that of patients with Parkinson's disease. This study corroborated the findings in rodent brain slices that chronic lithium treatment may block LTP. Whereas a deficit in LTP may underlie the therapeutic mechanism for treating psychiatric disorders such as bipolar affective disorder, it may simultaneously contribute to consequent appearance of tremor.


Assuntos
Transtorno Bipolar/fisiopatologia , Lítio/efeitos adversos , Potenciação de Longa Duração/efeitos dos fármacos , Neurônios/fisiologia , Parte Reticular da Substância Negra/fisiopatologia , Tremor/induzido quimicamente , Tremor/fisiopatologia , Idoso , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Estimulação Encefálica Profunda , Humanos , Masculino
3.
N Engl J Med ; 375(8): 730-9, 2016 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-27557301

RESUMO

BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).


Assuntos
Tremor Essencial/terapia , Tálamo/cirurgia , Terapia por Ultrassom , Atividades Cotidianas , Idoso , Método Duplo-Cego , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Qualidade de Vida , Terapia por Ultrassom/efeitos adversos , Terapia por Ultrassom/métodos , Ultrassonografia de Intervenção
4.
J Neurol Neurosurg Psychiatry ; 90(4): 474-482, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30337440

RESUMO

There are several different surgical procedures that are used to treat essential tremor (ET), including deep brain stimulation (DBS) and thalamotomy procedures with radiofrequency (RF), radiosurgery (RS) and most recently, focused ultrasound (FUS). Choosing a surgical treatment requires a careful presentation and discussion of the benefits and drawbacks of each. We conducted a literature review to compare the attributes and make an appraisal of these various procedures. DBS was the most commonly reported treatment for ET. One-year tremor reductions ranged from 53% to 63% with unilateral Vim DBS. Similar improvements were demonstrated with RF (range, 74%-90%), RS (range, 48%-63%) and FUS thalamotomy (range, 35%-75%). Overall, bilateral Vim DBS demonstrated more improvement in tremor reduction since both upper extremities were treated (range, 66%-78%). Several studies show continued beneficial effects from DBS up to five years. Long-term follow-up data also support RF and gamma knife radiosurgical thalamotomy treatments. Quality of life measures were similarly improved among patients who received all treatments. Paraesthesias, dysarthria and ataxia were commonly reported adverse effects in all treatment modalities and were more common with bilateral DBS surgery. Many of the neurological complications were transient and resolved after surgery. DBS surgery had the added benefit of programming adjustments to minimise stimulation-related complications. Permanent neurological complications were most commonly reported for RF thalamotomy. Thalamic DBS is an effective, safe treatment with a long history. For patients who are medically unfit or reluctant to undergo DBS, several thalamic lesioning methods have parallel benefits to unilateral DBS surgery. Each of these surgical modalities has its own nuance for treatment and patient selection. These factors should be carefully considered by both neurosurgeons and patients when selecting an appropriate treatment for ET.


Assuntos
Estimulação Encefálica Profunda/métodos , Tremor Essencial/terapia , Ablação por Radiofrequência/métodos , Radiocirurgia/métodos , Técnicas Estereotáxicas , Tálamo/cirurgia , Procedimentos Cirúrgicos Ultrassônicos/métodos , Protocolos Clínicos , Humanos , Procedimentos Neurocirúrgicos , Implantação de Prótese
5.
Mov Disord ; 34(2): 264-273, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30633810

RESUMO

BACKGROUND: Pantothenate kinase-associated neurodegeneration is a rare autosomal-recessive disorder, characterized by progressive neurodegeneration associated with brain iron accumulation. DBS has been trialed to treat related movement disorders, particularly dystonia. The objective of this study was to determine the outcome and safety of DBS for pantothenate kinase-associated neurodegeneration. METHODS: We performed a meta-analysis using independent participant data (n = 99) from 38 articles. Primary outcome was change in movement and disability scores of the Burke-Fahn-Marsden Dystonia Rating Scale 1 year postoperatively. Secondary outcomes were response rate and complications. RESULTS: Patients with classic-type (n = 58) and atypical-type (n = 15) pantothenate kinase-associated neurodegeneration were operated on at a median age of 11 and 31 years, respectively (P < 0.001). GPi was primarily targeted (n = 87). Mean dystonia movement score improved 1 year following GPi-DBS (-26%; 95% confidence interval, -37% to -15%), particularly in atypical versus classic cases (-45% vs -16%; P < 0.001). At least 30% improvement was observed in 34% of classic versus 73% of atypical cases (P = 0.04). Higher preoperative score and atypical type predicted larger improvement. GPi-DBS improved dystonia disability score in atypical (-31%; 95% confidence interval, -49% to -13%) but not classic (-5%; 95% confidence interval, -17% to 8%) cases. Prevalence of surgical infections (6%) and hardware failure (7%) was similar to other dystonia etiologies. Two patients died within 3 months. There was insufficient data to describe outcome > 1 year following GPi-DBS or with other DBS targets. Overall, small sample sizes limited generalizability. CONCLUSIONS: This meta-analysis provides level 4 evidence that GPi-DBS for pantothenate kinase-associated neurodegeneration may improve dystonia movement scores in classic type and atypical type and disability scores in atypical type 1 year postoperatively. © 2019 International Parkinson and Movement Disorder Society.


Assuntos
Estimulação Encefálica Profunda , Distonia/terapia , Neurodegeneração Associada a Pantotenato-Quinase/terapia , Transtornos Parkinsonianos/terapia , Adolescente , Adulto , Encéfalo/cirurgia , Criança , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Distonia/fisiopatologia , Distúrbios Distônicos/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurodegeneração Associada a Pantotenato-Quinase/complicações , Neurodegeneração Associada a Pantotenato-Quinase/fisiopatologia , Transtornos Parkinsonianos/complicações , Resultado do Tratamento , Adulto Jovem
6.
Magn Reson Med ; 79(6): 3122-3127, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29115692

RESUMO

PURPOSE: To develop a rapid pulse sequence for volumetric MR thermometry. METHODS: Simulations were carried out to assess temperature deviation, focal spot distortion/blurring, and focal spot shift across a range of readout durations and maximum temperatures for Cartesian, spiral-out, and retraced spiral-in/out (RIO) trajectories. The RIO trajectory was applied for stack-of-spirals 3D imaging on a real-time imaging platform and preliminary evaluation was carried out compared to a standard 2D sequence in vivo using a swine brain model, comparing maximum and mean temperatures measured between the two methods, as well as the temporal standard deviation measured by the two methods. RESULTS: In simulations, low-bandwidth Cartesian trajectories showed substantial shift of the focal spot, whereas both spiral trajectories showed no shift while maintaining focal spot geometry. In vivo, the 3D sequence achieved real-time 4D monitoring of thermometry, with an update time of 2.9-3.3 s. CONCLUSION: Spiral imaging, and RIO imaging in particular, is an effective way to speed up volumetric MR thermometry. Magn Reson Med 79:3122-3127, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Termometria/métodos , Animais , Encéfalo/diagnóstico por imagem , Simulação por Computador , Imagens de Fantasmas , Suínos
7.
Stereotact Funct Neurosurg ; 96(1): 60-64, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29433124

RESUMO

BACKGROUND: A recent randomized controlled trial investigating unilateral MRI-guided focused ultrasound (FUS) for essential tremor demonstrated efficacy. The long-term durability of this thalamotomy, however, is unknown. Furthermore, the feasibility of stimulating a previously lesioned target such as the thalamic nucleus ventralis intermedius (Vim) is poorly understood. We report a case of tremor recurrence, following an initially successful FUS thalamotomy, in which Vim-DBS was subsequently utilized to regain tremor control. METHODS: An 81-year-old right-handed female with medically refractory essential tremor (a Clinical Rating Scale for Tremor [CRST] value of 73) underwent left-sided FUS thalamotomy with initial abolition of right-upper extremity tremor. By the 6-month follow-up, there was complete recurrence of tremor (a CRST value of 76). The patient subsequently underwent left-sided Vim-DBS. RESULTS: Vim-DBS provided clinical improvement with a CRST value of 42 at the 3-month follow-up; the patient continues to do clinically well at the 6-month follow-up. This result mirrors previous reported cases of stimulation following radiofrequency and gamma-knife lesioning. Our literature review highlights several reasons for the waning of clinical benefit seen with lesional procedures. CONCLUSION: This case demonstrates that thalamic DBS can salvage a failed FUS thalamotomy and also the feasibility of stimulating a previously lesioned target.


Assuntos
Estimulação Encefálica Profunda/métodos , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/cirurgia , Ultrassonografia de Intervenção/métodos , Núcleos Ventrais do Tálamo/diagnóstico por imagem , Núcleos Ventrais do Tálamo/cirurgia , Idoso de 80 Anos ou mais , Feminino , Humanos , Recidiva , Terapia de Salvação/métodos , Resultado do Tratamento
8.
Neurosurg Focus ; 45(2): E11, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30064320

RESUMO

Drug addiction represents a significant public health concern that has high rates of relapse despite optimal medical therapy and rehabilitation support. New therapies are needed, and deep brain stimulation (DBS) may be an effective treatment. The past 15 years have seen numerous animal DBS studies for addiction to various drugs of abuse, with most reporting decreases in drug-seeking behavior with stimulation. The most common target for stimulation has been the nucleus accumbens, a key structure in the mesolimbic reward pathway. In addiction, the mesolimbic reward pathway undergoes a series of neuroplastic changes. Chief among them is a relative hypofunctioning of the prefrontal cortex, which is thought to lead to the diminished impulse control that is characteristic of drug addiction. The prefrontal cortex, as well as other targets involved in drug addiction such as the lateral habenula, hypothalamus, insula, and subthalamic nucleus have also been stimulated in animals, with encouraging results. Although animal studies have largely shown promising results, current DBS studies for drug addiction primarily use stimulation during active drug use. More data are needed on the effect of DBS during withdrawal in preventing future relapse. The published human experience for DBS for drug addiction is currently limited to several promising case series or case reports that are not controlled. Further animal and human work is needed to determine what role DBS can play in the treatment of drug addiction.


Assuntos
Encéfalo/cirurgia , Estimulação Encefálica Profunda , Transtornos Relacionados ao Uso de Substâncias/terapia , Núcleo Subtalâmico/cirurgia , Animais , Estimulação Encefálica Profunda/métodos , Humanos , Procedimentos Neurocirúrgicos/métodos , Resultado do Tratamento
9.
Neurosurg Focus ; 44(2): E3, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29385914

RESUMO

Although the use of focused ultrasound (FUS) in neurosurgery dates to the 1950s, its clinical utility was limited by the need for a craniotomy to create an acoustic window. Recent technological advances have enabled efficient transcranial delivery of US. Moreover, US is now coupled with MRI to ensure precise energy delivery and monitoring. Thus, MRI-guided transcranial FUS lesioning is now being investigated for myriad neurological and psychiatric disorders. Among the first transcranial FUS treatments is thalamotomy for the treatment of various tremors. The authors provide a technical overview of FUS thalamotomy for tremor as well as important lessons learned during their experience with this emerging technology.


Assuntos
Tremor Essencial/diagnóstico por imagem , Tremor Essencial/cirurgia , Imageamento por Ressonância Magnética/métodos , Procedimentos Neurocirúrgicos/métodos , Tálamo/diagnóstico por imagem , Tálamo/cirurgia , Humanos , Monitorização Neurofisiológica Intraoperatória/métodos , Cuidados Pós-Operatórios/métodos
10.
Acta Neurochir (Wien) ; 159(11): 2193-2207, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28913667

RESUMO

PURPOSE: The aim of this systematic review is to evaluate the long-term endocrine outcomes and postoperative complications following endoscopic vs. microscopic transsphenoidal resection (TSR) for the treatment of acromegaly. METHODS: A literature review was performed, and studies with at least five patients who underwent TSR for acromegaly, reporting biochemical remission criteria and long-term remission outcomes were included. Data extracted from each study included surgical technique, perioperative complications, biochemical remission criteria, and long-term remission outcomes. RESULTS: Fifty-two case series from 1976 to 2016 met the inclusion criteria, comprising 4375 patients. Thirty-six reports were microsurgical (n = 3144) and 13 were endoscopic (n = 940). Three studies compared microsurgical (n = 111) to endoscopic TSR outcomes (n = 180). The overall initial and long-term remission rates were 58.2 vs. 57.4% and 69.2 vs. 70.2% for the microsurgical and endoscopic groups, respectively. For microadenomas, the initial and long-term remission rates were 77.6 vs. 82.2% and 76.9 vs. 73.5% for microsurgical and endoscopic approaches, respectively. For macroadenomas, the initial and long-term remission rates were 46.9 vs. 60.0% and 40.2 vs. 61.5% for microsurgical and endoscopic approaches, respectively. The rates of postoperative CSF leak were 3.0 vs. 2.3% for the microscopic and endoscopic groups, respectively. The rates of hypopituitarism and transient diabetes insipidus were 6.7 vs. 6.4% and 9.0 vs. 7.8% for the microscopic and endoscopic groups, respectively. CONCLUSIONS: Both endoscopic and microsurgical approaches for TSR of growth hormone-secreting adenomas are viable treatment options for patients with acromegaly, and yield similarly high rates of remission under the most current consensus criteria.


Assuntos
Acromegalia/cirurgia , Endoscopia/métodos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Microcirurgia/métodos , Neoplasias Hipofisárias/cirurgia , Vazamento de Líquido Cefalorraquidiano/epidemiologia , Humanos , Hipopituitarismo , Complicações Pós-Operatórias , Osso Esfenoide/cirurgia , Resultado do Tratamento
11.
EMBO J ; 31(5): 1203-16, 2012 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-22234183

RESUMO

Memory is essential for our normal daily lives and our sense of self. Ca(2+) influx through the NMDA-type glutamate receptor (NMDAR) and the ensuing activation of the Ca(2+) and calmodulin-dependent protein kinase (CaMKII) are required for memory formation and its physiological correlate, long-term potentiation (LTP). The Ca(2+) influx induces CaMKII binding to the NMDAR to strategically recruit CaMKII to synapses that are undergoing potentiation. We generated mice with two point mutations that impair CaMKII binding to the NMDAR GluN2B subunit. Ca(2+)-triggered postsynaptic accumulation is largely abrogated for CaMKII and destabilized for TARPs, which anchor AMPA-type glutamate receptors (AMPAR). LTP is reduced by 50% and phosphorylation of the AMPAR GluA1 subunit by CaMKII, which enhances AMPAR conductance, impaired. The mutant mice learn the Morris water maze (MWM) as well as WT but show deficiency in recall during the period of early memory consolidation. Accordingly, the activity-driven interaction of CaMKII with the NMDAR is important for recall of MWM memory as early as 24 h, but not 1-2 h, after training potentially due to impaired consolidation.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Memória , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Camundongos , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Mutação de Sentido Incorreto , Mutação Puntual , Ligação Proteica , Receptores de N-Metil-D-Aspartato/genética
12.
Mov Disord ; 30(14): 1937-43, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26769606

RESUMO

BACKGROUND: Thalamic deep brain stimulation (DBS) has largely replaced radiofrequency thalamotomy as the treatment of choice for disabling, medication-refractory essential tremor. Recently, the development of transcranial, high-intensity focused ultrasound has renewed interest in thalamic lesioning. The purpose of this study is to compare functional outcomes and quality of life in essential tremor patients treated with either bilateral Vim DBS or unilateral procedures (focused ultrasound or DBS). We hypothesized that all three would effectively treat the dominant hand and positively impact functional outcomes and quality of life as measured with the Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire. METHODS: This is a retrospective study of medication-refractory essential tremor patients treated at the University of Virginia with bilateral Vim DBS (n = 57), unilateral Vim DBS (n = 13), or unilateral focused ultrasound Vim thalamotomy (n = 15). Tremor was rated for all patients before and after treatment, using the Clinical Rating Scale for Tremor and Quality of Life in Essential Tremor Questionnaire. RESULTS: Patients undergoing bilateral DBS treatment had more baseline tremor and worse quality of life scores. Patients had significant improvements in tremor symptoms and quality of life with all three treatments. Both DBS procedures improved axial tremor. No difference was seen in the degree of improvement in upper extremity tremor score, disability, or overall quality of life between bilateral and either unilateral procedure. CONCLUSIONS: Bilateral thalamic DBS improves overall tremor more than unilateral DBS or focused ultrasound treatment; however, unilateral treatments are equally effective in treating contralateral hand tremor. Despite the greater overall tremor reduction with bilateral DBS, there is no difference in disability or quality of life comparing bilateral versus unilateral treatments.


Assuntos
Estimulação Encefálica Profunda/métodos , Tremor Essencial/diagnóstico , Tremor Essencial/terapia , Qualidade de Vida/psicologia , Tálamo , Idoso , Tremor Essencial/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia de Intervenção
13.
Pituitary ; 18(2): 211-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25724315

RESUMO

BACKGROUND: Transsphenoidal selective adenomectomy is the first-line treatment for Cushing's disease. At experienced centers, early remission rates after transsphenoidal surgery range from 65 to 98%, however disease relapse frequently occurs with rates ranging from 2 to 35% at long-term follow up. METHODS: This article discusses recently reported studies on the surgical outcomes from transsphenoidal surgery for Cushing's disease. CONCLUSIONS: One of the keys to a successful long-term surgical outcome is meticulous dissection using the adenoma's pseudocapsule as a surgical plane for complete resection. MRI-negative and invasive ACTH-secreting adenomas pose particular challenges for pituitary surgeons.


Assuntos
Adenoma Hipofisário Secretor de ACT/cirurgia , Adenoma/cirurgia , Hipofisectomia , Hipersecreção Hipofisária de ACTH/cirurgia , Adenoma Hipofisário Secretor de ACT/complicações , Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma/complicações , Adenoma/diagnóstico , Humanos , Recidiva Local de Neoplasia , Neoplasia Residual , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/etiologia , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
14.
Stereotact Funct Neurosurg ; 93(2): 140-146, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25765151

RESUMO

BACKGROUND: Patients treated with deep brain stimulation (DBS) often develop symptom progression. If safe, focused ultrasound (FUS) lesioning could be used for patients unable to undergo further DBS surgery. OBJECTIVE: To test the feasibility and safety of MR-guided FUS surgery in the setting of a previously implanted DBS system. METHODS: Three preclinical experiments were designed to test feasibility and safety. Hydrogels were implanted with an electrode, and FUS lesions were targeted adjacently. Cadavers were implanted with a thalamic electrode, and FUS lesions were targeted in the contralateral thalamus. Finally, DBS systems were implanted in swine, and FUS lesioning was targeted to the contralateral thalamus, MRI was used to assess the treatments, and histological analyses were performed at 2 days and at 1 month. RESULTS: In gel experiments and cadavers, FUS resulted in target heating to 29-32°C without any heating at the electrode. In animal experiments, there were no FUS-related MRI signal changes near the electrode. Histological analysis showed typical FUS lesions with no evidence of damage surrounding the electrode tracts. CONCLUSIONS: FUS is feasible in the setting of a preimplanted DBS device. There was minimal heating of the device during the procedure and no apparent FUS-related tissue injury. © 2015 S. Karger AG, Basel.

16.
J Biol Chem ; 287(27): 22838-53, 2012 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-22589537

RESUMO

To maintain genomic integrity DNA damage response (DDR), signaling pathways have evolved that restrict cellular replication and allow time for DNA repair. CCNG2 encodes an unconventional cyclin homolog, cyclin G2 (CycG2), linked to growth inhibition. Its expression is repressed by mitogens but up-regulated during cell cycle arrest responses to anti-proliferative signals. Here we investigate the potential link between elevated CycG2 expression and DDR signaling pathways. Expanding our previous finding that CycG2 overexpression induces a p53-dependent G(1)/S phase cell cycle arrest in HCT116 cells, we now demonstrate that this arrest response also requires the DDR checkpoint protein kinase Chk2. In accord with this finding we establish that ectopic CycG2 expression increases phosphorylation of Chk2 on threonine 68. We show that DNA double strand break-inducing chemotherapeutics stimulate CycG2 expression and correlate its up-regulation with checkpoint-induced cell cycle arrest and phospho-modification of proteins in the ataxia telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) signaling pathways. Using pharmacological inhibitors and ATM-deficient cell lines, we delineate the DDR kinase pathway promoting CycG2 up-regulation in response to doxorubicin. Importantly, RNAi-mediated blunting of CycG2 attenuates doxorubicin-induced cell cycle checkpoint responses in multiple cell lines. Employing stable clones, we test the effect that CycG2 depletion has on DDR proteins and signals that enforce cell cycle checkpoint arrest. Our results suggest that CycG2 contributes to DNA damage-induced G(2)/M checkpoint by enforcing checkpoint inhibition of CycB1-Cdc2 complexes.


Assuntos
Divisão Celular/fisiologia , Ciclina G2/genética , Dano ao DNA/fisiologia , Doxorrubicina/farmacologia , Fase G2/fisiologia , Transdução de Sinais/efeitos dos fármacos , Animais , Antibióticos Antineoplásicos/farmacologia , Proteínas Mutadas de Ataxia Telangiectasia , Proteína Quinase CDC2 , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Divisão Celular/efeitos dos fármacos , Quinase do Ponto de Checagem 2 , Ciclina B/metabolismo , Ciclina B1/metabolismo , Ciclina G2/metabolismo , Quinases Ciclina-Dependentes , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fase G2/efeitos dos fármacos , Genes cdc/efeitos dos fármacos , Genes cdc/fisiologia , Células HCT116 , Humanos , Camundongos , Células NIH 3T3 , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/fisiopatologia , Proteína Oncogênica p21(ras)/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Interferente Pequeno/genética , Transdução de Sinais/fisiologia , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
17.
Asian J Neurosurg ; 18(1): 40-44, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37056893

RESUMO

Objective Trigeminal neuralgia (TN) is a debilitating syndrome characterized by paroxysmal facial pain in one or more divisions of the trigeminal nerve. The etiology and treatment paradigms are still controversial. The endoscopically-assisted procedure has not yet been described in percutaneous procedures for TN. The aim of this study was to assess the utility and feasibility of endoscopic-assisted percutaneous approaches for trigeminal rhizotomy in TN. Methods This study comprised eight cadaveric sides heads that underwent an endoscopically assisted percutaneous approach using Hakanson's anterior puncture method for targeting the foramen ovale. Results V3 exiting the foramen ovale was easily visualized with the endoscope on all sides. While approaching the foramen ovale, distal branches of V3 such as the lingual and inferior alveolar nerves were first identified as they traveled between the medial and lateral pterygoid muscles. These branches were then traced proximally to the V3 trunk deep to the lateral pterygoid. Large arteries and veins were easily visualized and avoided in the trajectory to the foramen ovale. No gross injury to any neurovascular structure along the course of the needle insertion was identified. Conclusion We found that endoscopic-assisted percutaneous approach to the foramen ovale is feasible and allows for accurate canalization and anatomical identification of the precise location for rhizotomy under direct visualization. Such a procedure, after it is confirmed in patients, could offer a new technique for reducing unsuccessful canalization and could improve outcomes.

18.
Otolaryngol Clin North Am ; 55(3): 607-632, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35490039

RESUMO

Facial pain is a common medical complaint that is easily misdiagnosed. As a result, this pain often goes mistreated. Despite this, there are a variety of pharmacologic, surgical, and neuromodulatory options for the treatment of facial pain. In this review, the authors detail the forms of facial pain and their treatment options. They discuss the common medications used in the first-line treatment of facial pain and the second-line surgical and neuromodulatory options available to patients when pharmacologic options fail.


Assuntos
Rizotomia , Neuralgia do Trigêmeo , Dor Facial/diagnóstico , Dor Facial/etiologia , Dor Facial/cirurgia , Humanos , Resultado do Tratamento , Neuralgia do Trigêmeo/diagnóstico , Neuralgia do Trigêmeo/cirurgia
19.
J Craniovertebr Junction Spine ; 13(4): 378-389, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36777909

RESUMO

Background: Steadily increasing expenditure in the United States health-care system has led to a shift toward a value-based model that focuses on quality of care and cost-effectiveness. Operations involving the spine rank among some of the most common and expensive procedures performed in operating rooms nationwide. Patient-reported outcomes measures (PROMs) are a useful tool for reporting levels of outcome and analyzing patient recovery but are both under-utilized and nonstandardized in spine surgery. Methods: We conducted a systematic review of the literature using the PubMed database, focusing on the most commonly utilized PROMs for spine disease as well as spinal deformity. The benefits and drawbacks of these PROMs were then summarized and compared. Results: Spine-specific PROMs were based on the class of disease. The most frequently utilized PROMs were the Neck Disability Index and the modified Japanese Orthopaedic Association scale; the Oswestry Disability Index and the Roland-Morris Disability Questionnaire; and the Scoliosis Research Society 22-item questionnaire (SRS-22) for cervicothoracic spine disease, lumbar spine disease, and spinal deformity, respectively. Conclusion: We found limited, though effective, use of PROMs targeting specific classes of disease within spine surgery. Therefore, we advocate for increased use of PROMs in spine surgery, in both the research and clinical settings. PROM usage can help physicians assess subjective outcomes in standard ways that can be compared across patients and institutions, more uniquely tailor treatment to individual patients, and engage patients in their own medical care.

20.
J Craniovertebr Junction Spine ; 13(3): 224-232, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36263337

RESUMO

Cat scratch disease (CSD), caused by Bartonella henselae, may atypically present with vertebral osteomyelitis. Antibiotic regimens are tailored to presentation, which is markedly variable and not well defined for any atypical disease. In cases of spinal instability, the use of antibiotics alone may not be sufficient. Atlantoaxial instability caused by osteomyelitis is a rare complication of CSD. In this report, we describe the rare case of vertebral osteomyelitis complicated by atlantoaxial instability, requiring both antibiotics and atlantoaxial fusion. We discuss our case, surgical technique, rationale, and outcome. In addition, we conducted a systematic review of the literature of vertebral osteomyelitis in pediatric secondary to B. henselae. A 2-year-old child presented with a 2-month history of irritability, fever, and rigid neck pain along with a recent history of feline exposure. Physical examination revealed cervical tenderness and decreased range of motion. Computed tomography (CT) showed osteolysis of the right C1 lateral mass and pars articularis; T1-weighted magnetic resonance imaging with contrast showed enhancement around the right C1 lateral mass. The titer for B. henselae was high. A diagnosis of cat scratch osteomyelitis with cervical instability was made, for which the patient underwent surgery with atlantoaxial fusion. Postoperative imaging demonstrated resolution of the contrast-enhanced lesion. At 6-year follow-up, the patient showed no signs of residual complications from surgical intervention with a solid fusion. Our review revealed 44 cases of pediatric CSD vertebral osteomyelitis. Conservative management with antibiotic employed in 86% while antibiotics with surgical intervention in 14% of the cases. Surgical intervention was most often in the form of incision for drainage and decompression without fusion. Average follow-up 10 months with 86% achieved complete resolution. Cervical instability caused by osteolysis is a rare complication of CSD. This can subsequently lead to vertebral instability, requiring definitive surgical intervention.

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