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1.
Neurosurgery ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767366

RESUMO

BACKGROUND AND OBJECTIVES: The management of blunt cerebrovascular injuries (BCVIs) remains an important topic within trauma and neurosurgery today. There remains a lack of consensus within the literature and significant variation across institutions. The purpose of this study was to evaluate management of BCVI at a large, tertiary referral trauma center. METHODS: Institutional Review Board approval was obtained to conduct a retrospective review of patients with BCVI at our Level 1 Trauma Center. Computed tomography angiography was used to identify BCVI for each patient. Patient information was collected, and statistical analysis was performed. With the included risk factors for ischemic complications, a novel scoring system based on ischemic risk, the "Memphis Score," was developed and evaluated to grade BCVI. RESULTS: Two hundred seventeen patients with BCVI from July 2020 to August 2022 were identified. The most common mechanism of injury was motor vehicle collision (141, 65.0%). Vertebral arteries were the most common vessel injured (136, 51.1%) with most injuries occurring at a high cervical location (101, 38.0%). Denver Grade 1 injuries (89, 33.5%) and a Memphis Score of 1 were most frequent (172, 64.6%), and initial anticoagulation with heparin drip was initiated 56.7% of the time (123). Endovascular treatment was required in 24 patients (11.1%) and was usually performed in the first 48 hours (15, 62.5%). While Denver Grade (P = .019) and Memphis Score (P < .00001) were significantly higher in those patients undergoing endovascular treatment, only the Memphis Score demonstrated a significant difference between those patients who had stroke or worsening on follow-up imaging and those who did not (P = .0009). CONCLUSION: Although BCVI management has improved since early investigative efforts, institutions must evaluate and share their data to help clarify outcomes. The novel "Memphis Score" presents a standardized framework to communicate ischemic risk and guide management of BCVI.

4.
Interv Neuroradiol ; : 15910199231154707, 2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36760041

RESUMO

A 41-year-old female presented with a headache and left inferior quadrantanopia. Imaging demonstrated a clot spanning the atrium of the ventricle to the superior parietal lobule (SPL), with a small arteriovenous malformation (AVM) nidus outside the atrium of the ventricle. The nidus was supplied by parieto-occipital arterial (P4) feeders with a single atrial draining vein. Pre-operative embolization of a pedicle with Onyx provided a surgical marker. A parietal craniotomy was performed with a trans-cortical SPL approach. During AVM resection, the draining vein was injured, which was stabilized using a temporary clip to "spot weld" the defect and continue nidus dissection with patent venous outflow. After careful dissection, coagulation, and division of all the arterial feeders, the AVM was mobilized and the draining vein was clipped, coagulated, and divided. Follow-up indocyanine green angiography and cerebral angiography both confirmed complete resection of the AVM. The patient consented to the procedure and to publication.

5.
Cureus ; 14(10): e30248, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36381781

RESUMO

Primary glioblastoma of the spinal cord (sGB) is a rare and challenging diagnosis. In the diagnostic algorithm, reversible causes should be considered while the diagnosis of sGB is under evaluation. We present a case of cervical sGB mimicking neuroschistosomiasis. A 21-year-old Somali man presented with neck pain, sensory disturbances, and spastic tetraplegia. Cervical spine magnetic resonance imaging with contrast showed a heterogeneously enhancing intramedullary mass spanning from the level of the C1 to T3 vertebrae. Cerebrospinal fluid analysis showed a lymphocytic predominance and elevated protein. Due to the patient's history of poorly treated schistosomiasis, praziquantel and dexamethasone were initiated while the diagnostic work-up was completed. Three days after the patient was discharged to a rehabilitation facility where he experienced worsened motor function with radiographic progression of the lesion and increased cord edema. The patient underwent a surgical biopsy which confirmed a diagnosis of primary sGB. sGB is an unusual diagnosis that can masquerade as a non-neoplastic lesion. However, the diagnosis of sGB should be considered in patients with an intramedullary spinal cord lesion who exhibit rapid radiographic and clinical progression.

7.
PLoS One ; 16(4): e0249591, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33819286

RESUMO

Traumatic spinal cord injury (SCI) is a devastating neurological condition that involves both primary and secondary tissue loss. Various cytotoxic events including hypoxia, hemorrhage and blood lysis, bioenergetic failure, oxidative stress, endoplasmic reticulum (ER) stress, and neuroinflammation contribute to secondary injury. The HIF prolyl hydroxylase domain (PHD/EGLN) family of proteins are iron-dependent, oxygen-sensing enzymes that regulate the stability of hypoxia inducible factor-1α (HIF-1α) and also mediate oxidative stress caused by free iron liberated from the lysis of blood. PHD inhibition improves outcome after experimental intracerebral hemorrhage (ICH) by reducing activating transcription factor 4 (ATF4)-driven neuronal death. As the ATF4-CHOP (CCAAT-enhancer-binding protein homologous protein) pathway plays a role in the pathogenesis of contusive SCI, we examined the effects of PHD inhibition in a mouse model of moderate T9 contusive SCI in which white matter damage is the primary driver of locomotor dysfunction. Pharmacological inhibition of PHDs using adaptaquin (AQ) moderately lowers acute induction of Atf4 and Chop mRNAs and prevents the acute decline of oligodendrocyte (OL) lineage mRNAs, but does not improve long-term recovery of hindlimb locomotion or increase chronic white matter sparing. Conditional genetic ablation of all three PHD isoenzymes in OLs did not affect Atf4, Chop or OL mRNAs expression levels, locomotor recovery, and white matter sparing after SCI. Hence, PHDs may not be suitable targets to improve outcomes in traumatic CNS pathologies that involve acute white matter injury.


Assuntos
Fator 4 Ativador da Transcrição/antagonistas & inibidores , Estresse do Retículo Endoplasmático , Locomoção , Pró-Colágeno-Prolina Dioxigenase/antagonistas & inibidores , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/fisiopatologia , Fator de Transcrição CHOP/antagonistas & inibidores , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismos da Medula Espinal/metabolismo , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo
8.
Oper Neurosurg (Hagerstown) ; 20(3): 310-316, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33372226

RESUMO

BACKGROUND: Acute subdural hematomas (aSDHs) occur in approximately 10% to 20% of all closed head injury and represent a significant cause of morbidity and mortality in traumatic brain injury patients. Conventional craniotomy is an invasive intervention with the potential for excess blood loss and prolonged postoperative recovery time. OBJECTIVE: To evaluate the outcomes of minimally invasive endoscopy for evacuation of aSDHs in a pilot feasibility study. METHODS: We retrospectively reviewed the records of consecutive patients with aSDHs who underwent surgical treatment at our institution with minimally invasive endoscopy using the Apollo/Artemis Neuro Evacuation Device (Penumbra, Alameda, California) between April 2015 and July 2018. RESULTS: The study cohort comprised three patients. The Glasgow Coma Scale on admission was 15 for all 3 patients, median preoperative hematoma volume was 49.5 cm3 (range 44-67.8 cm3), median postoperative degree of hematoma evacuation was 88% (range 84%-89%), and median modified Rankin Scale at discharge was 1 (range 0-3). CONCLUSION: Endoscopic evacuation of aSDHs can be a safe and effective alternative to craniotomy in appropriately selected patients. Further studies are needed to refine the selection criteria for endoscopic aSDH evacuation and evaluate its long-term outcomes.


Assuntos
Hematoma Subdural Agudo , Craniotomia , Endoscopia , Escala de Coma de Glasgow , Hematoma Subdural Agudo/diagnóstico por imagem , Hematoma Subdural Agudo/cirurgia , Humanos , Estudos Retrospectivos
9.
Neurosurgery ; 88(3): 523-530, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33269390

RESUMO

BACKGROUND: Patients who survive aneurysmal subarachnoid hemorrhage (aSAH) are at risk for delayed neurological deficits (DND) and cerebral infarction. In this exploratory cohort comparison analysis, we compared in-hospital outcomes of aSAH patients administered a low-dose intravenous heparin (LDIVH) infusion (12 U/kg/h) vs those administered standard subcutaneous heparin (SQH) prophylaxis for deep vein thrombosis (DVT; 5000 U, 3 × daily). OBJECTIVE: To assess the safety and efficacy of LDIVH in aSAH patients. METHODS: We retrospectively analyzed 556 consecutive cases of aSAH patients whose aneurysm was secured by clipping or coiling at a single institution over a 10-yr period, including 233 administered the LDIVH protocol and 323 administered the SQH protocol. Radiological and outcome data were compared between the 2 cohorts using multivariable logistic regression and propensity score-based inverse probability of treatment weighting (IPTW). RESULTS: The unadjusted rate of cerebral infarction in the LDIVH cohort was half that in SQH cohort (9 vs 18%; P = .004). Multivariable logistic regression showed that patients in the LDIVH cohort were significantly less likely than those in the SQH cohort to have DND (odds ratio (OR) 0.53 [95% CI: 0.33, 0.85]) or cerebral infarction (OR 0.40 [95% CI: 0.23, 0.71]). Analysis following IPTW showed similar results. Rates of hemorrhagic complications, heparin-induced thrombocytopenia and DVT were not different between cohorts. CONCLUSION: This cohort comparison analysis suggests that LDIVH infusion may favorably influence the outcome of patients after aSAH. Prospective studies are required to further assess the benefit of LDIVH infusion in patients with aSAH.


Assuntos
Anticoagulantes/administração & dosagem , Infarto Cerebral/prevenção & controle , Heparina/administração & dosagem , Doenças do Sistema Nervoso/prevenção & controle , Hemorragia Subaracnóidea/tratamento farmacológico , Adulto , Idoso , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/etiologia , Estudos de Coortes , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico por imagem , Doenças do Sistema Nervoso/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem
10.
Interv Neuroradiol ; 27(3): 388-390, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33070683

RESUMO

Ruptured vertebrobasilar dissecting aneurysms require urgent, often challenging treatment as they have with a high re-hemorrhage rate within the first 24 hours. The patient is a 57-year-old woman who presented with severe-sudden onset headache. Further work up showed a ruptured dissecting aneurysm of the caudal loop of the posterior inferior cerebellar artery (PICA) with associated narrowing distally, in the ascending limb. The aneurysm was immediately occluded with a Woven Endobridge (WEB) device (MicroVention, Tustin, CA, USA) while flow diversion treatment of the diseased ascending limb was postponed. Follow-up angiography three months later showed complete occlusion of the aneurysm, as well as healing of the diseased distal vessel, obviating the need for further intervention. WEB embolization of a ruptured dissecting posterior circulation aneurysm provided an excellent outcome for this patient.


Assuntos
Aneurisma Roto , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Dissecação , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Interdiscip Neurosurg ; 22: 100878, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32837915

RESUMO

COVID-19 patients are increasingly understood to develop multisystem manifestations, including neurologic involvement. We report the case of a 42-year old COVID-19 positive patient with a fatal intracerebral hemorrhage (ICH). The patient presented with fever and dyspnea, requiring intubation due to medical complications. After prolonged sedation and anticoagulation, the patient suddenly developed bilaterally fixed and dilated pupils, caused by a right-sided intracranial hemorrhage with uncal herniation. The course of this case illustrates the delicate balance between hypercoagulability and coagulation factor depletion; especially in the intubated and sedated patient, in whom regular neurological assessments are impeded. As we expand our understanding of the neurological ramifications of COVID-19, clinicians need to be increasingly aware of the precarious coagulation balance.

12.
J Neurotrauma ; 37(21): 2277-2291, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32605423

RESUMO

Yucatan miniature pigs (YMPs) are similar to humans in spinal cord size as well as physiological and neuroanatomical features, making them a useful model for human spinal cord injury. However, little is known regarding pig gait kinematics, especially on a treadmill. In this study, 12 healthy YMPs were assessed during bipedal and/or quadrupedal stepping on a treadmill at six speeds (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 km/h). Kinematic parameters, including limb coordination and proximal and distal limb angles, were measured. Findings indicate that YMPs use a lateral sequence footfall pattern across all speeds. Stride and stance durations decreased with increasing speed whereas swing duration showed no significant change. Across all speeds assessed, no significant differences were noted between hindlimb stepping parameters for bipedal or quadrupedal gait with the exception of distal limb angular kinematics. Specifically, significant differences were observed between locomotor tasks during maximum flexion (quadrupedal > bipedal), total excursion (bipedal > quadrupedal), and the phase relationship between the timing of maximum extension between the right and left hindlimbs (bipedal > quadrupedal). Speed also impacted maximum flexion and right-left phase relationships given that significant differences were found between the fastest speed (3.5 km/h) relative to each of the other speeds. This study establishes a methodology for bipedal and quadrupedal treadmill-based kinematic testing in healthy YMPs. The treadmill approach used was effective in recruiting primarily the spinal circuitry responsible for the basic stepping patterns as has been shown in cats. We recommend 2.5 km/h (0.7 m/sec) as a target walking gait for pre-clinical studies using YMPs, which is similar to that used in cats.


Assuntos
Análise da Marcha/métodos , Porco Miniatura/fisiologia , Animais , Fenômenos Biomecânicos , Feminino , Marcha , Modelos Animais , Suínos
13.
BMC Neurol ; 20(1): 144, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32312245

RESUMO

BACKGROUND: Vagal nerve stimulation (VNS) can be an effective therapy for patients with epilepsy refractory to anti-epileptic drugs or intracranial surgery. While generally well tolerated, it has been associated with laryngospasm, hoarseness, coughing, dyspnea, throat and atypical chest pain, cardiac symptoms such as bradycardia and occasionally asystole. We report on a patient receiving vagal nerve stimulation who experienced severe typical anginal chest pain during VNS firing without any evidence of cardiac ischemia or dysfunction. Thus, the pain appeared to be neuropathic from the stimulation itself rather than nociceptive secondary to an effect on heart function. CASE PRESENTATION: A 29-year-old man, with a history of intractable frontal lobe epilepsy refractory to seven anti-epileptic medications and subsequent intracranial surgery, underwent VNS implantation without complications. On beginning stimulation, he began to have intermittent chest pain that corresponded temporally to his intermittent VNS firing. The description of his pain was pathognomonic of ischemic cardiac chest pain. On initial evaluation, he displayed Levine's sign and reported crushing substernal chest pain radiating to the left arm, as well as shortness of breath walking upstairs that improved with rest. He underwent an extensive cardiac workup, including 12-lead ECG, cardiac stress test, echocardiogram, 12-day ambulatory cardiac monitoring, and continuous ECG monitoring each with and without stimulation of his device. The workup was consistently negative. Inability to resolve the pain necessitated the disabling and eventual removal of the device. CONCLUSION: To our knowledge, this is the first report of pseudoanginal chest pain associated with VNS. This occurrence prompted our review of the mechanisms of cardiac chest pain and suggests that vagal afferents may convey anginal pain separately or in parallel with known spinal cord pain mechanisms. These insights into the physiology of chest pain may be of general interest and important to surgeons implanting VNS devices who may potentially encounter such symptoms.


Assuntos
Dor no Peito , Estimulação do Nervo Vago/efeitos adversos , Adulto , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Dor no Peito/fisiopatologia , Epilepsia Resistente a Medicamentos/terapia , Humanos , Masculino
14.
World Neurosurg ; 138: e642-e651, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32173551

RESUMO

OBJECTIVE: Endovascular thrombectomy (ET) for acute large vessel occlusion reduces infarct size, and it should hypothetically decrease the incidence of major ischemic strokes requiring decompressive craniectomy (DC). The aim of this retrospective cohort study is to determine trends in the utilization of ET versus DC for stroke in the United States over a 10-year span. METHODS: We extracted data from the Nationwide Inpatient Sample using International Classification of Diseases-9/10 codes from 2006-2016. Patients with a primary diagnosis of stroke were included. Baseline demographics, outcomes, and hospital charges were analyzed. RESULTS: The study cohort comprised 14,578,654 patients diagnosed with stroke. During the study period, DC and ET were performed in 124,718 and 62,637 patients, respectively. The number of stroke patients who underwent either ET or DC increased by 266% from 2006 to 2016. During that time period, the ET utilization rate increased (0.19% in 2006 to 14.07% in 2016, P < 0.0004), whereas the DC utilization rate decreased (7.07% in 2006 to 6.43% in 2016, P < 0.0001). In 2015, the utilization rate of ET (9.73%) exceeded that of DC (9.67%). ET-treated patients had shorter hospitalization durations (mean 8.8 vs. 16.8 days, P < 0.0001), lower mortality (16.2% vs. 19.3%), higher likelihood of discharge home (27.1% vs. 24.1%, P < 0.0001), and reduced hospital charges (mean $189,724 vs. $261,314, P < 0.0001). CONCLUSIONS: We identified an inverse relationship between national trends in rising ET and diminishing DC utilization for stroke treatment over a recent decade. Although direct causation cannot be inferred, our findings suggest that ET curtails the necessity for DC.


Assuntos
Isquemia Encefálica/cirurgia , Craniectomia Descompressiva/tendências , Procedimentos Endovasculares/tendências , Acidente Vascular Cerebral/cirurgia , Trombectomia/tendências , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/economia , Estudos de Coortes , Craniectomia Descompressiva/economia , Demografia , Procedimentos Endovasculares/economia , Feminino , Custos de Cuidados de Saúde , Preços Hospitalares , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Acidente Vascular Cerebral/economia , Trombectomia/economia , Resultado do Tratamento
15.
Acta Neurochir Suppl ; 127: 15-19, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31407057

RESUMO

Aneurysmal subarachnoid hemorrhage (aSAH) remains a significant cause of stroke disability despite gradual reductions in physical morbidity and mortality. Heparin is an effective anti-inflammatory agent and may potentially prevent delayed neurological injury in the days to weeks after the hemorrhage. Various human studies have shown the safety of a continuous infusion of low-dose unfractionated heparin in the setting of subarachnoid hemorrhage as well as its efficacy in minimizing delayed neurological deficits including symptomatic cerebral vasospasm, vasospasm-related infarction, and cognitive dysfunction. Studies have also shown mixed results with low-molecular-weight heparin usage in this patient population. Heparin treatment is not associated with significant hemorrhagic complications; however, vigilance is essential for early detection of heparin-induced thrombocytopenia in order to prevent devastating sequelae. Multicenter randomized controlled trials are necessary for objective characterization of the effects of heparin.


Assuntos
Anticoagulantes , Heparina , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Anticoagulantes/uso terapêutico , Heparina/uso terapêutico , Humanos , Acidente Vascular Cerebral/etiologia , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Vasoespasmo Intracraniano/tratamento farmacológico
16.
BMC Neurol ; 19(1): 214, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470816

RESUMO

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder usually associated with specific medical conditions that cause a disturbance of the CNS homeostasis. It has seldom been reported to be a consequence of an iatrogenic intervention causing intracranial hypotension. CASE PRESENTATION: We report the case of an individual 69-year-old male presenting with headache and blurred vision following cerebrospinal fluid (CSF) leak from resection of a sellar mass. The patient developed the condition following removal of the lumbar drain post-operatively. Magnetic Resonance Imaging showed bilateral occipital, parieto-occipital, and cerebellar T2 FLAIR hyper-intensities, suggesting a radiological diagnosis of posterior reversible encephalopathy syndrome (PRES). The patient's symptoms started to improve shortly afterwards and had completely resolved at 3 months follow-up. CONCLUSIONS: The absence of severe hypertension and presence of an intraoperative CSF leak requiring placement of the lumbar drain suggests that decreased CSF volume and associated reactive hyperemia could have a role in the pathophysiology of the disease.


Assuntos
Drenagem/métodos , Cefaleia/etiologia , Síndrome da Leucoencefalopatia Posterior/etiologia , Idoso , Cerebelo , Drenagem/efeitos adversos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino
17.
Cureus ; 11(6): e4940, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31431845

RESUMO

Background  Cerebral venous thrombosis (CVT) is a rare cerebrovascular disorder, comprising <1% of all strokes. The incidence of CVT is higher in females but a small number of cases suggest that men have a higher risk for CVT in high elevation. The aim of this retrospective cohort study is to investigate this gender-related relationship and to describe the baseline characteristics and treatment outcomes of patients who suffered CVT at high altitude in eastern Nepal. Methods  We conducted a retrospective analysis of 21 consecutive patients with CVT at a tertiary care center in Nepal from July 2017 to January 2018. Clinical data, radiologic characteristics, therapeutic strategies, and outcomes were analyzed. The Glasgow Outcome Scale (GOS) at discharge was reported for each patient.  Result The study cohort comprised 21 patients (76% males) with a mean of 56 years. Medical comorbidities included hypertension (76%) and diabetes mellitus (57%). All patients received low-molecular-weight heparin therapy (LMWH). Eight patients (38%) underwent decompressive craniectomy while the remaining 13 (62%) were treated with medical therapy alone. The GOS at discharge was 5 in 57%, 2-4 in 33%, and 1 in 10%. Conclusion  In our series, men were found to have a higher risk for CVT at high altitude. The reversal in the gender ratio could be related to elevation, but could also be confounded by alcoholism. Increasingly sophisticated imaging techniques, such as computed tomography venography (CTV) and magnetic resonance venography (MRV), have facilitated the diagnosis of CVT. LMWH is a safe and easily accessible treatment option, especially in developing countries. Further studies are needed to assess the incidence and prevalence of CVT in the developing world, to establish the gender-related trends.

18.
Proc Natl Acad Sci U S A ; 116(33): 16593-16602, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31346086

RESUMO

Mutant huntingtin (mHTT), the causative protein in Huntington's disease (HD), associates with the translocase of mitochondrial inner membrane 23 (TIM23) complex, resulting in inhibition of synaptic mitochondrial protein import first detected in presymptomatic HD mice. The early timing of this event suggests that it is a relevant and direct pathophysiologic consequence of mHTT expression. We show that, of the 4 TIM23 complex proteins, mHTT specifically binds to the TIM23 subunit and that full-length wild-type huntingtin (wtHTT) and mHTT reside in the mitochondrial intermembrane space. We investigated differences in mitochondrial proteome between wtHTT and mHTT cells and found numerous proteomic disparities between mHTT and wtHTT mitochondria. We validated these data by quantitative immunoblotting in striatal cell lines and human HD brain tissue. The level of soluble matrix mitochondrial proteins imported through the TIM23 complex is lower in mHTT-expressing cell lines and brain tissues of HD patients compared with controls. In mHTT-expressing cell lines, membrane-bound TIM23-imported proteins have lower intramitochondrial levels, whereas inner membrane multispan proteins that are imported via the TIM22 pathway and proteins integrated into the outer membrane generally remain unchanged. In summary, we show that, in mitochondria, huntingtin is located in the intermembrane space, that mHTT binds with high-affinity to TIM23, and that mitochondria from mHTT-expressing cells and brain tissues of HD patients have reduced levels of nuclearly encoded proteins imported through TIM23. These data demonstrate the mechanism and biological significance of mHTT-mediated inhibition of mitochondrial protein import, a mechanism likely broadly relevant to other neurodegenerative diseases.


Assuntos
Proteína Huntingtina/metabolismo , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas Mutantes/metabolismo , Proteostase , Linhagem Celular , Núcleo Celular/metabolismo , Córtex Cerebral/patologia , Corpo Estriado/patologia , Humanos , Doença de Huntington , Membranas Mitocondriais/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Proteínas Mitocondriais/metabolismo , Ligação Proteica , Proteoma/metabolismo
19.
World Neurosurg ; 129: e35-e39, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31042595

RESUMO

BACKGROUND: Spontaneous intracranial hemorrhage (ICH) of the cerebellum can be life threatening because of mass effect on the brainstem and fourth ventricle. Suboccipital craniectomy is currently the treatment of choice for cerebellar ICH evacuation. Minimally invasive surgery (MIS) is currently being investigated for the treatment of supratentorial ICH. However, its utility for cerebellar ICH is unknown. The aim of this multicenter, retrospective cohort study is to evaluate the outcomes of MIS for cerebellar ICH. METHODS: We retrospectively reviewed the records of all patients with cerebellar ICH who underwent MIS using either the Apollo or Artemis Neuro Evacuation Device (Penumbra Inc., Alameda, California, USA) at 3 institutions from May 2015 to July 2018. Data from each contributing center were deidentified and pooled for analysis. RESULTS: The study cohort comprised 6 patients with a median age of 62.5 years. The median pre- and postoperative Glasgow Coma Scale scores were 10.5 and 15, respectively. The median degree of hematoma evacuation was 97.5% (range, 79%-100%). There were no procedural complications, but 1 patient required subsequent craniectomy (retreatment rate 17%). The median discharge modified Rankin scale score was 4, including 3 patients who improved to functional independence at follow-up durations of 3 months. Two patients died from medical complications (mortality rate 33%). CONCLUSIONS: MIS could represent a reasonable alternative to conventional surgery for the treatment of appropriately selected patients with cerebellar ICH. However, further studies are needed to clarify the perioperative and long-term risk to benefit profiles of this technique.


Assuntos
Doenças Cerebelares/cirurgia , Drenagem/instrumentação , Hemorragias Intracranianas/cirurgia , Neuroendoscopia/instrumentação , Idoso , Cerebelo/cirurgia , Estudos de Coortes , Drenagem/métodos , Feminino , Hematoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Neuroendoscopia/métodos , Neuronavegação/métodos , Estudos Retrospectivos
20.
Cureus ; 11(2): e4070, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-31016097

RESUMO

Spinal cord herniation (SCH) is an uncommon traumatic event that should be considered in patients with vertebral fractures who develop an unusual constellation of autonomic and motor deficits. Herein, we describe a case of rapidly deteriorating neurological function following cervical spine fracture including sequelae such as bilateral lower-extremity weakness, loss of upper extremity motor function, and priapism. Decompression of the spinal cord allowed for the identification of the unusual herniation of the spinal cord and prevention of any further worsening of the neurological injury. Hyperflexion of the cervical spine upon traumatic impact provided the impetus for vertebral retropulsion and subsequent incarceration of the spinal cord. This phenomenon should be considered in the setting of acute traumatic injury to the cervical spinal cord. Surgical intervention is likely to allow the preservation of the remaining neurological function.

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