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2.
J Pain ; 23(8): 1343-1357, 2022 08.
Article En | MEDLINE | ID: mdl-35292377

Neuropathic pain in rodents can be driven by ectopic spontaneous activity (SA) generated by sensory neurons in dorsal root ganglia (DRG). The recent demonstration that SA in dissociated human DRG neurons is associated with reported neuropathic pain in patients enables a detailed comparison of pain-linked electrophysiological alterations driving SA in human DRG neurons to alterations that distinguish SA in nociceptors from SA in low-threshold mechanoreceptors (LTMRs) in rodent neuropathy models. Analysis of recordings from dissociated somata of patient-derived DRG neurons showed that SA and corresponding pain in both sexes were significantly associated with the three functional electrophysiological alterations sufficient to generate SA in the absence of extrinsic depolarizing inputs. These include enhancement of depolarizing spontaneous fluctuations of membrane potential (DSFs), which were analyzed quantitatively for the first time in human DRG neurons. The functional alterations were indistinguishable from SA-driving alterations reported for nociceptors in rodent chronic pain models. Irregular, low-frequency DSFs in human DRG neurons closely resemble DSFs described in rodent nociceptors while differing substantially from the high-frequency sinusoidal oscillations described in rodent LTMRs. These findings suggest that conserved physiological mechanisms of SA in human nociceptor somata can drive neuropathic pain despite documented cellular differences between human and rodent DRG neurons. PERSPECTIVE: Electrophysiological alterations in human sensory neurons associated with patient-reported neuropathic pain include all three of the functional alterations that logically can promote spontaneous activity. The similarity of distinctively altered spontaneous depolarizations in human DRG neurons and rodent nociceptors suggests that spontaneously active human nociceptors can persistently promote neuropathic pain in patients.


Neuralgia , Nociceptors , Action Potentials/physiology , Animals , Female , Ganglia, Spinal/physiology , Humans , Male , Nociceptors/physiology , Rodentia , Sensory Receptor Cells
3.
Pain ; 161(11): 2494-2501, 2020 11.
Article En | MEDLINE | ID: mdl-32826754

SARS-CoV-2 has created a global crisis. COVID-19, the disease caused by the virus, is characterized by pneumonia, respiratory distress, and hypercoagulation and can be fatal. An early sign of infection is loss of smell, taste, and chemesthesis-loss of chemical sensation. Other neurological effects of the disease have been described, but not explained. It is now apparent that many of these neurological effects (for instance joint pain and headache) can persist for at least months after infection, suggesting a sensory neuronal involvement in persistent disease. We show that human dorsal root ganglion (DRG) neurons express the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 at the RNA and protein level. We also demonstrate that SARS-CoV-2 and coronavirus-associated factors and receptors are broadly expressed in human DRG at the lumbar and thoracic level as assessed by bulk RNA sequencing. ACE2 mRNA is expressed by a subset of nociceptors that express MRGPRD mRNA, suggesting that SARS-CoV-2 may gain access to the nervous system through entry into neurons that form free nerve endings at the outermost layers of skin and luminal organs. Therefore, DRG sensory neurons are a potential target for SARS-CoV-2 invasion of the peripheral nervous system, and viral infection of human nociceptors may cause some of the persistent neurological effects seen in COVID-19.


Betacoronavirus , Coronavirus Infections/metabolism , Ganglia, Spinal/metabolism , Nervous System Diseases/metabolism , Nociceptors/metabolism , Peptidyl-Dipeptidase A/biosynthesis , Pneumonia, Viral/metabolism , Spike Glycoprotein, Coronavirus/biosynthesis , Adult , Aged , Angiotensin-Converting Enzyme 2 , COVID-19 , Coronavirus Infections/genetics , Female , Ganglia, Spinal/virology , Gene Expression , Humans , Male , Middle Aged , Nervous System Diseases/genetics , Nervous System Diseases/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
4.
J Neurooncol ; 148(2): 327-334, 2020 Jun.
Article En | MEDLINE | ID: mdl-32358642

OBJECTIVE: Dose escalation via stereotactic radiation therapy techniques has been necessary for hepatobiliary malignancies in the primary and oligometastatic setting, but such dose escalation is challenging for spine metastases due to spinal cord proximity. Here, we investigate the role of spine stereotactic radiosurgery (SSRS) in the management of such metastases. METHODS: We retrospectively reviewed patients treated with SSRS to spinal metastases from hepatobiliary malignancies between 2004 and 2017 at our Institution. We used the Kaplan-Meier method to calculate overall survival (OS) and local control (LC) and Cox regression analysis to identify factors associated with disease-related outcomes. RESULTS: We identified 28 patients treated to 43 spinal metastases with SSRS for either HCC or cholangiocarcinoma. The 1-year LC and OS were 85% and 23%, respectively. The median time to death was 6.2 months, while median time to local failure was not reached. Tumor volume > 60 cc (SHR 6.65, p = 0.03) and Bilsky ≥ 1c (SHR 4.73, p = 0.05) predicted for poorer LC, while BED10 > 81 Gy trended towards better local control (SHR 4.35, p = 0.08). Child-Pugh Class (HR 3.02, p = 0.003), higher PRISM Group (HR 3.49, p = 0.001), and systemic disease progression (HR 3.65, p = 0.001) were associated with worse mortality based on univariate modeling in patients treated with SSRS; on multivariate analysis, PRISM Group (HR 2.28, p = 0.03) and systemic disease progression (HR 2.67, p = 0.03) remained significant. Four patients (10%) developed compression deformity and one patient (2%) developed radiation neuritis. CONCLUSION: SSRS provides durable local control in patients with metastatic hepatobiliary malignancies, with higher BED necessary to ensure excellent LC. PRISM scoring is a promising prognostic tool to aid SSRS patient selection.


Digestive System Neoplasms/diagnosis , Digestive System Neoplasms/pathology , Radiosurgery , Spinal Neoplasms/diagnosis , Spinal Neoplasms/radiotherapy , Adult , Aged , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Patient Selection , Retrospective Studies , Spinal Neoplasms/secondary , Treatment Outcome
5.
J Neurosurg Spine ; : 1-9, 2020 Jan 03.
Article En | MEDLINE | ID: mdl-31899882

OBJECTIVE: The proximity of the spinal cord to compressive metastatic lesions limits radiosurgical dosing. Open surgery is used to create safe margins around the spinal cord prior to spinal stereotactic radiosurgery (SSRS) but carries the risk of potential surgical morbidity and interruption of systemic oncological treatment. Spinal laser interstitial thermotherapy (SLITT) in conjunction with SSRS provides local control with less morbidity and a shorter interval to resume systemic treatment. The authors present a comparison between SLITT and open surgery in patients with metastatic thoracic epidural spinal cord compression to determine the advantages and disadvantages of each method. METHODS: This is a matched-group design study comprising patients from a single institution with metastatic thoracic epidural spinal cord compression that was treated either with SLITT or open surgery. The two cohorts defined by the surgical treatment comprised patients with epidural spinal cord compression (ESCC) scores of 1c or higher and were deemed suitable for either treatment. Demographics, pre- and postoperative ESCC scores, histology, morbidity, hospital length of stay (LOS), complications, time to radiotherapy, time to resume systemic therapy, progression-free survival (PFS), and overall survival (OS) were compared between groups. RESULTS: Eighty patients were included in this analysis, 40 in each group. Patients were treated between January 2010 and December 2016. There was no significant difference in demographics or clinical characteristics between the cohorts. The SLITT cohort had a smaller postoperative decrease in the extent of ESCC but a lower estimated blood loss (117 vs 1331 ml, p < 0.001), shorter LOS (3.4 vs 9 days, p < 0.001), lower overall complication rate (5% vs 35%, p = 0.003), fewer days until radiotherapy or SSRS (7.8 vs 35.9, p < 0.001), and systemic treatment (24.7 vs 59 days, p = 0.015). PFS and OS were similar between groups (p = 0.510 and p = 0.868, respectively). CONCLUSIONS: The authors' results have shown that SLITT plus XRT is not inferior to open decompression surgery plus XRT in regard to local control, with a lower rate of complications and faster resumption of oncological treatment. A prospective randomized controlled study is needed to compare SLITT with open decompressive surgery for ESCC.

6.
Brain ; 142(5): 1215-1226, 2019 05 01.
Article En | MEDLINE | ID: mdl-30887021

Neuropathic pain encompasses a diverse array of clinical entities affecting 7-10% of the population, which is challenging to adequately treat. Several promising therapeutics derived from molecular discoveries in animal models of neuropathic pain have failed to translate following unsuccessful clinical trials suggesting the possibility of important cellular-level and molecular differences between animals and humans. Establishing the extent of potential differences between laboratory animals and humans, through direct study of human tissues and/or cells, is likely important in facilitating translation of preclinical discoveries to meaningful treatments. Patch-clamp electrophysiology and RNA-sequencing was performed on dorsal root ganglia taken from patients with variable presence of radicular/neuropathic pain. Findings establish that spontaneous action potential generation in dorsal root ganglion neurons is associated with radicular/neuropathic pain and radiographic nerve root compression. Transcriptome analysis suggests presence of sex-specific differences and reveals gene modules and signalling pathways in immune response and neuronal plasticity related to radicular/neuropathic pain that may suggest therapeutic avenues and that has the potential to predict neuropathic pain in future cohorts.


Electrophysiological Phenomena/physiology , Ganglia, Spinal/physiopathology , Neuralgia/genetics , Neuralgia/physiopathology , Transcriptome/physiology , Cells, Cultured , Female , Humans , Male , Prospective Studies , Retrospective Studies
7.
World Neurosurg ; 124: e580-e594, 2019 Apr.
Article En | MEDLINE | ID: mdl-30641236

BACKGROUND: Spinal ependymomas are rare, with an incidence of 1 per 100,000. Given the paucity of data for higher grade II and III disease, the management and patterns of care require further investigation. METHODS: Our study of 1345 patients with higher-grade spinal ependymoma used χ2 tests and simple and multivariable logistic regression models to assess demographic and clinical factors associated with therapy. Kaplan-Meier and log-rank tests were used to assess overall survival (OS). RESULTS: Most grade II patients received surgery alone (81.1%) compared with 36.8% of grade III. Approximately 60% of patients with grade III ependymomas received radiotherapy (RT) versus 15.3% of grade II (P < 0.001). Patients living ≤32 km (20 miles) from a facility were more likely to receive RT (P < 0.001) than were those living further away. On multivariable logistic regression, grade (grade III, odds ratio, 8.6; P < 0.001) and facility distance were significantly associated with receipt of RT (P < 0.0001). The 5-year and 10-year OS was 94.7%/85.1% for patients with grade II disease and 58.2%/46.4% for grade III disease (P < 0.0001). OS was highest at facilities treating an average of 15 patients over 10 years, corresponding to the top 81st percentile in volume. The 10-year OS was 92.6% at facilities treating at least 15 patients and 88.0% at facilities treating 6-14 patients. CONCLUSIONS: Approximately 40% of patients with grade III ependymomas do not receive immediate adjuvant therapy, which may be related to distance from a facility. Patients with this rare tumor may benefit from multidisciplinary care at facilities with a larger volume.

8.
J Neurosci ; 38(5): 1124-1136, 2018 01 31.
Article En | MEDLINE | ID: mdl-29255002

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect experienced by cancer patients receiving treatment with paclitaxel. The voltage-gated sodium channel 1.7 (Nav1.7) plays an important role in multiple preclinical models of neuropathic pain and in inherited human pain phenotypes, and its gene expression is increased in dorsal root ganglia (DRGs) of paclitaxel-treated rats. Hence, the potential of change in the expression and function of Nav1.7 protein in DRGs from male rats with paclitaxel-related CIPN and from male and female humans with cancer-related neuropathic pain was tested here. Double immunofluorescence in CIPN rats showed that Nav1.7 was upregulated in small DRG neuron somata, especially those also expressing calcitonin gene-related peptide (CGRP), and in central processes of these cells in the superficial spinal dorsal horn. Whole-cell patch-clamp recordings in rat DRG neurons revealed that paclitaxel induced an enhancement of ProTx II (a selective Nav1.7 channel blocker)-sensitive sodium currents. Bath-applied ProTx II suppressed spontaneous action potentials in DRG neurons occurring in rats with CIPN, while intrathecal injection of ProTx II significantly attenuated behavioral signs of CIPN. Complementarily, DRG neurons isolated from segments where patients had a history of neuropathic pain also showed electrophysiological and immunofluorescence results indicating an increased expression of Nav1.7 associated with spontaneous activity. Nav1.7 was also colocalized in human cells expressing transient receptor potential vanilloid 1 and CGRP. Furthermore, ProTx II decreased firing frequency in human DRGs with spontaneous action potentials. This study suggests that Nav1.7 may provide a potential new target for the treatment of neuropathic pain, including chemotherapy (paclitaxel)-induced neuropathic pain.SIGNIFICANCE STATEMENT This work demonstrates that the expression and function of the voltage-gated sodium channel Nav1.7 are increased in a preclinical model of chemotherapy-induced peripheral neuropathy (CIPN), the most common treatment-limiting side effect of all the most common anticancer therapies. This is key as gain-of-function mutations in human Nav1.7 recapitulate both the distribution and pain percept as shown by CIPN patients. This work also shows that Nav1.7 is increased in human DRG neurons only in dermatomes where patients are experiencing acquired neuropathic pain symptoms. This work therefore has major translational impact, indicating an important novel therapeutic avenue for neuropathic pain as a class.


Antineoplastic Agents, Phytogenic/toxicity , Ganglia, Spinal/drug effects , NAV1.7 Voltage-Gated Sodium Channel/biosynthesis , NAV1.7 Voltage-Gated Sodium Channel/drug effects , Neuralgia/chemically induced , Neuralgia/metabolism , Paclitaxel/toxicity , Action Potentials/drug effects , Animals , Calcitonin Gene-Related Peptide/biosynthesis , Calcitonin Gene-Related Peptide/genetics , Female , Ganglia, Spinal/cytology , Humans , Hyperalgesia/chemically induced , Hyperalgesia/psychology , Male , Patch-Clamp Techniques , Primary Cell Culture , Rats , Rats, Sprague-Dawley , Sodium Channel Blockers/pharmacology , Spider Venoms/pharmacology , Up-Regulation/drug effects
9.
Pain ; 158(3): 417-429, 2017 03.
Article En | MEDLINE | ID: mdl-27902567

Here, it is shown that paclitaxel-induced neuropathy is associated with the development of spontaneous activity (SA) and hyperexcitability in dorsal root ganglion (DRG) neurons that is paralleled by increased expression of low-voltage-activated calcium channels (T-type; Cav3.2). The percentage of DRG neurons showing SA and the overall mean rate of SA were significantly higher at day 7 in rats receiving paclitaxel treatment than in rats receiving vehicle. Cav3.2 expression was increased in L4-L6 DRG and spinal cord segments in paclitaxel-treated rats, localized to small calcitonin gene-related peptide and isolectin B4 expressing DRG neurons and to glial fibrillary acidic protein-positive spinal cord cells. Cav3.2 expression was also co-localized with toll-like receptor 4 (TLR4) in both the DRG and the dorsal horn. T-type current amplitudes and density were increased at day 7 after paclitaxel treatment. Perfusion of the TLR4 agonist lipopolysaccharide directly activated DRG neurons, whereas this was prevented by pretreatment with the specific T-type calcium channel inhibitor ML218 hydrochloride. Paclitaxel-induced behavioral hypersensitivity to mechanical stimuli in rats was prevented but not reversed by spinal administration of ML218 hydrochloride or intravenous injection of the TLR4 antagonist TAK242. Paclitaxel induced inward current and action potential discharges in cultured human DRG neurons, and this was blocked by ML218 hydrochloride pretreatment. Furthermore, ML218 hydrochloride decreased firing frequency in human DRG, where spontaneous action potentials were present. In summary, Cav3.2 in concert with TLR4 in DRG neurons appears to contribute to paclitaxel-induced neuropathy.


Calcium Channels, T-Type/metabolism , Ganglia, Spinal/pathology , Hyperalgesia/etiology , Paclitaxel , Peripheral Nervous System Diseases/complications , Peripheral Nervous System Diseases/pathology , Sensory Receptor Cells/metabolism , Animals , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/pharmacology , Azabicyclo Compounds/therapeutic use , Benzamides/therapeutic use , Calcitonin Gene-Related Peptide/metabolism , Calcium Channel Blockers/therapeutic use , Disease Models, Animal , Gene Expression Regulation/drug effects , Humans , Male , Paclitaxel/adverse effects , Paclitaxel/pharmacology , Pain Threshold/drug effects , Pain Threshold/physiology , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/prevention & control , Rats , Rats, Sprague-Dawley , Sensory Receptor Cells/drug effects , Spinal Cord/drug effects , Spinal Cord/metabolism , Sulfonamides/therapeutic use , Toll-Like Receptor 4/antagonists & inhibitors , Toll-Like Receptor 4/metabolism
10.
J Neurosci ; 35(39): 13487-500, 2015 Sep 30.
Article En | MEDLINE | ID: mdl-26424893

Peripheral neuropathy is dose limiting in paclitaxel cancer chemotherapy and can result in both acute pain during treatment and chronic persistent pain in cancer survivors. The hypothesis tested was that paclitaxel produces these adverse effects at least in part by sensitizing transient receptor potential vanilloid subtype 1 (TRPV1) through Toll-like receptor 4 (TLR4) signaling. The data show that paclitaxel-induced behavioral hypersensitivity is prevented and reversed by spinal administration of a TRPV1 antagonist. The number of TRPV1(+) neurons is increased in the dorsal root ganglia (DRG) in paclitaxel-treated rats and is colocalized with TLR4 in rat and human DRG neurons. Cotreatment of rats with lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides (LPS-RS), a TLR4 inhibitor, prevents the increase in numbers of TRPV1(+) neurons by paclitaxel treatment. Perfusion of paclitaxel or the archetypal TLR4 agonist LPS activated both rat DRG and spinal neurons directly and produced acute sensitization of TRPV1 in both groups of cells via a TLR4-mediated mechanism. Paclitaxel and LPS sensitize TRPV1 in HEK293 cells stably expressing human TLR4 and transiently expressing human TRPV1. These physiological effects also are prevented by LPS-RS. Finally, paclitaxel activates and sensitizes TRPV1 responses directly in dissociated human DRG neurons. In summary, TLR4 was activated by paclitaxel and led to sensitization of TRPV1. This mechanism could contribute to paclitaxel-induced acute pain and chronic painful neuropathy. Significance statement: In this original work, it is shown for the first time that paclitaxel activates peripheral sensory and spinal neurons directly and sensitizes these cells to transient receptor potential vanilloid subtype 1 (TRPV1)-mediated capsaicin responses via Toll-like receptor 4 (TLR4) in multiple species. A direct functional interaction between TLR4 and TRPV1 is shown in rat and human dorsal root ganglion neurons, TLR4/TRPV1-coexpressing HEK293 cells, and in both rat and mouse spinal cord slices. Moreover, this is the first study to show that this interaction plays an important role in the generation of behavioral hypersensitivity in paclitaxel-related neuropathy. The key translational implications are that TLR4 and TRPV1 antagonists may be useful in the prevention and treatment of chemotherapy-induced peripheral neuropathy in humans.


Antineoplastic Agents, Phytogenic/pharmacology , Paclitaxel/pharmacology , Sensory Receptor Cells/drug effects , TRPV Cation Channels/antagonists & inhibitors , Toll-Like Receptor 4/drug effects , Animals , Antineoplastic Agents, Phytogenic/antagonists & inhibitors , Calcium/metabolism , Excitatory Postsynaptic Potentials/drug effects , Ganglia, Spinal/cytology , Ganglia, Spinal/drug effects , HEK293 Cells , Humans , Hyperalgesia/chemically induced , Hyperalgesia/physiopathology , Male , Mice , Mice, Inbred C57BL , Paclitaxel/antagonists & inhibitors , Pain Measurement/drug effects , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Spinal Cord/drug effects , Toll-Like Receptor 4/antagonists & inhibitors
11.
Arq Neuropsiquiatr ; 63(3B): 855-8, 2005 Sep.
Article En | MEDLINE | ID: mdl-16258670

Spinal extradural meningeal cysts are typically formed by a thin fibrotic membranous capsule, macroscopically similar that of an arachnoid membrane, filled by cerebro spinal fluid and related to a nerve root or to the posterior midline. Ventral location is extremely rare and when it occurs they usually cause spinal cord herniation through the ventral dural gap. A 61 year-old man who began with a two years long history of insidious tetraparesis, spasticity and hyperreflexia in lower extremities, and flaccid atrophy of upper limbs, without sensory manifestations, is presented. Investigation through magnetic resonance imaging demonstrated an extensive spinal ventral extradural cystic collection from C6 to T11. The lesion was approached through a laminectomy and a cyst-peritoneal shunt was introduced. The cyst reduced in size significantly and the patient is asymptomatic over a 48 months follow-up. This is the first reported case of a spontaneous ventral extradural spinal meningeal cyst causing cord compression. Cyst-peritoneal shunt was effective in the treatment of the case and it should be considered in cases in which complete resection of the cyst is made more difficult or risky by the need of more aggressive surgical maneuvers.


Arachnoid Cysts/surgery , Spinal Cord Compression/surgery , Spinal Cord Diseases/surgery , Thoracic Vertebrae/pathology , Arachnoid Cysts/complications , Arachnoid Cysts/pathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Myelography , Peritoneal Cavity/pathology , Spinal Cord Compression/etiology , Spinal Cord Compression/pathology , Spinal Cord Diseases/complications , Spinal Cord Diseases/pathology , Treatment Outcome
12.
Arq Neuropsiquiatr ; 63(3A): 676-80, 2005 Sep.
Article En | MEDLINE | ID: mdl-16172723

We present the case of a 47 years old woman submitted to an endovascular trapping of a left cavernous internal carotid artery aneurysm, in which the distal balloon was inflated, as usually done, within the cavernous segment of the internal carotid artery, different from the proximal one which was inflated inside the carotid canal due to technical problems. Consequently, a clinical picture of Raeder's paratrigeminal neuralgia took place. This is the first case report in the literature with theses characteristics. A review of the anatomic pathways and further considerations about the possible pathophysiological mechanisms involved are presented.


Balloon Occlusion/adverse effects , Blepharoptosis/etiology , Carotid Artery, Internal/diagnostic imaging , Intracranial Aneurysm/therapy , Miosis/etiology , Trigeminal Neuralgia/etiology , Blepharoptosis/physiopathology , Cerebral Angiography , Female , Humans , Intracranial Aneurysm/diagnostic imaging , Magnetic Resonance Imaging , Middle Aged , Miosis/physiopathology , Syndrome , Trigeminal Neuralgia/physiopathology
13.
Arq. neuropsiquiatr ; 63(3A): 676-680, set. 2005. ilus
Article En | LILACS | ID: lil-409056

Apresentamos o caso de uma mulher de 47 anos submetida a obliteração endovascular de um aneurisma gigante de carótida interna cavernosa à esquerda, no qual o balão distal foi inflado, tal como usual, dentro do segmento cavernoso da artéria carótida interna, diferente do proximal, o qual foi inflado dentro do canal carotídeo devido a problemas técnicos. Conseqüentemente, um quadro clínico de neuralgia paratrigeminal de Raeder se instalou. Este é o primeiro relato na literatura com estas características. Uma revisão das vias anatômicas e maiores considerações a respeito de possíveis mecanismos fisiopatológicos envolvidos são apresentados.


Female , Humans , Middle Aged , Balloon Occlusion/adverse effects , Blepharoptosis/etiology , Carotid Artery, Internal , Intracranial Aneurysm/therapy , Miosis/etiology , Trigeminal Neuralgia/etiology , Blepharoptosis/physiopathology , Cerebral Angiography , Intracranial Aneurysm , Magnetic Resonance Imaging , Miosis/physiopathology , Syndrome , Trigeminal Neuralgia/physiopathology
14.
Arq Neuropsiquiatr ; 61(2A): 241-7, 2003 Jun.
Article Pt | MEDLINE | ID: mdl-12806503

Between 1993 and 1999, 44 patients submitted to resection of an expansible intradural extramedullary lesion who filled protocol requirements of appropriate follow up were studied. Patients were constituted by 43.2% female and 56.8% male. The mean age was 32.9 years old. Lesion most common location was at the thoracic spine, with 45.5% of the cases, followed by the lumbar level with 18.2%. Tumor extension varied from 1 to 7 vertebral segments, with an average of 2.5 levels. Schwannoma, with 65,9% of the cases, was the most frequent lesion, followed by meningioma with 20.5%. There were 2 cases of neurofibroma and 1 case of paraganglioma, neuroenteric cyst, metastasis and malignant schwannoma. The evolution was of improvement in 56.8%, stability in 31.8% and of worsening in 11.4%. There was no mortality related to the surgical procedure. All cases of worsening had total resection and they had lesions located in the thoracic segment. Total resection is the ideal modality of surgical treatment. However, at the thoracic level, where the peculiarities of spine irrigation prevail, surgical morbidade may be higher (p=0.014).


Meningioma/surgery , Neurilemmoma/surgery , Spinal Cord Neoplasms/surgery , Adolescent , Adult , Aged , Child , Female , Humans , Male , Meningioma/diagnosis , Middle Aged , Neurilemmoma/diagnosis , Neurofibroma/diagnosis , Neurofibroma/surgery , Prognosis , Retrospective Studies , Spinal Cord Neoplasms/diagnosis
15.
Arq Neuropsiquiatr ; 61(2A): 274-6, 2003 Jun.
Article En | MEDLINE | ID: mdl-12806511

A 5 year-old boy with a cerebellar gangliocytoma with a peripheral right facial paresis and ataxia is presented. His MRI showed a heterogenous, diffuse lesion, isointense on T1 and hyperintense on T2-weigthed sequences, involving the right cerebellar hemisphere with direct extension into the right facial nerve. The present case is the first description of a gangliocytoma with direct facial nerve invasion, as demonstrated for the facial nerve paresis and supported by MRI and surgical inspection.


Cerebellar Neoplasms/diagnosis , Cranial Nerve Neoplasms/diagnosis , Facial Nerve Diseases/diagnosis , Ganglioneuroma/diagnosis , Ataxia/etiology , Cerebellar Neoplasms/complications , Child, Preschool , Cranial Nerve Neoplasms/complications , Facial Nerve Diseases/complications , Facial Paralysis/etiology , Ganglioneuroma/complications , Humans , Male
16.
Arq. neuropsiquiatr ; 61(2A): 241-247, Jun. 2003. ilus, tab, graf
Article Pt | LILACS | ID: lil-339493

Entre 1993 e 1999 foram estudados 44 pacientes que preencheram requisitos protocolares de seguimento adequado e que foram submetidos a ressecção de processo expansivo extramedular intradural. Os pacientes eram constituídos por 43,2 por cento de mulheres e por 56,8 por cento de homens. A média da idade foi 32,9 anos. A localização da lesão foi mais comum na região torácica, com 45,5 por cento dos casos, seguida da lombar com 18,2 por cento. A extensão tumoral variou de 1 a 7 segmentos vertebrais, com uma média de 2,5 níveis. O schwanoma foi o tipo histológico mais comum com 65,9 por cento, seguido dos meningiomas com 20,5 por cento. Houve 2 casos de neurofibroma e 1 caso de paraganglioma, cisto neuroentorico, metástase e schwanoma maligno. A evolução foi de melhora em 56,8 por cento, estabilidade em 31,8 por cento e de piora em 11,4 por cento. Não houve mortalidade relacionada ao procedimento cirúrgico. Todos os casos de piora tiveram ressecção total e eram localizados no segmento torácico. A ressecção total é a modalidade ideal de tratamento cirúrgico. No entanto, no nível toracico, onde predominam as peculiaridades de irrigação da medula, a morbidade cirúrgica pode ser mais elevada (p=0,014)


Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Meningioma , Neurilemmoma , Spinal Cord Neoplasms , Meningioma , Neurilemmoma , Prognosis , Retrospective Studies , Spinal Cord Neoplasms
17.
Arq. neuropsiquiatr ; 61(2A): 274-276, Jun. 2003. ilus
Article En | LILACS | ID: lil-339501

A 5 year-old boy with a cerebellar gangliocytoma with a peripheral right facial paresis and ataxia is presented. His MRI showed a heterogenous, diffuse lesion, isointense on T1 and hyperintense on T2-weigthed sequences, involving the right cerebellar hemisphere with direct extension into the right facial nerve. The present case is the first description of a gangliocytoma with direct facial nerve invasion, as demonstrated for the facial nerve paresis and supported by MRI and surgical inspection


Humans , Male , Child, Preschool , Cerebellar Neoplasms , Cranial Nerve Neoplasms , Facial Nerve Diseases , Ganglioneuroma , Ataxia , Cerebellar Neoplasms , Cranial Nerve Neoplasms , Facial Nerve Diseases , Facial Paralysis , Ganglioneuroma
18.
Arq Neuropsiquiatr ; 61(1): 79-82, 2003 Mar.
Article Pt | MEDLINE | ID: mdl-12715024

Cavernomas are vascular malformations that typically affect the white matter of cerebral hemispheres and brain stem. They are angiographically occult lesions that depend on magnetic resonance imaging (MRI) for their diagnosis, presenting a hypointense perilesional ring caused by hemossiderin deposition as seen in T2 sequences. The ventricular location is rare, and image features may differ. We present two cases with diagnosis made only by histopathologic examination, due to a lack of classic image findings. Cavernous hemangiomas must be included in the differential diagnosis of intraventricular tumors, and total surgical resection is the treatment of choice. Perilesional ring as demonstrated by MRI, must not be expected when dealing with such lesions.


Cerebral Ventricle Neoplasms/diagnosis , Hemangioma, Cavernous/diagnosis , Magnetic Resonance Imaging , Adolescent , Cerebral Ventricle Neoplasms/surgery , Diagnosis, Differential , Female , Hemangioma, Cavernous/surgery , Humans , Male , Middle Aged
19.
Arq. neuropsiquiatr ; 61(1): 79-82, mar. 2003. ilus, tab
Article Pt | LILACS | ID: lil-331163

Cavernomas säo malformações vasculares que frequentemente acometem a substância branca dos hemisférios cerebrais e tronco encefálico. São angiograficamente ocultas e têm como principal método diagnóstico a ressonância magnética, em que tipicamente se observa nas sequências ponderadas em T2, um halo perilesional hipointenso devido a deposiçäo de hemossiderina no tecido adjacente. A localizaçäo ventricular é considerada rara, e suas características de imagem na ressonância magnética diferem, podendo näo apresentar tal halo. Apresentamos dois casos nos quais o diagnóstico foi feito somente com exame histopatológico, devido a ausência dos critérios de imagem que permitiriam a suspeita de tal lesäo. Os cavernomas devem ser incluidos no diagnóstico diferencial dos processos expansivos intraventriculares, sendo a ressecçäo cirurgica completa a melhor modalidade de tratamento para estas lesöes


Humans , Male , Female , Adolescent , Middle Aged , Cerebral Ventricle Neoplasms , Hemangioma, Cavernous , Magnetic Resonance Imaging , Cerebral Ventricle Neoplasms , Diagnosis, Differential , Hemangioma, Cavernous
20.
Arq Neuropsiquiatr ; 60(3-B): 818-22, 2002 Sep.
Article Pt | MEDLINE | ID: mdl-12364954

Between 1993 and 1999, in the Divisions of Neurosurgery of the Hospital Nossa Senhora das Graças and the Hospital de Clínicas in Curitiba, Paraná, Brazil, 35 patients harboring intramedullary spinal cord tumors who were submitted to microsurgery were analyzed. There were 24 males (68.6%) and average age was 32.9 years. The main location, with 40% of cases, was the thoracic level, followed by cervical and cervico-thoracic levels with 25.7%. Neurological exam, carried out between 6 and 12 months after surgery, showed that 42.9% of patients improved, 34.3% were stable and 22.9% presented neurological worsening. Total resection was obtained in 57.2% of cases and subtotal in 37.1%. In 5.7% of patients a biopsy was the accomplished procedure. Total resection was more often obtained among patients with ependymomas (13 out of 17) than with astrocytomas (5 out of 12). However, degree of resection and tumor histology did not interfere in postoperative morbidity. Factors as sex, age and tumor's size also did not demonstrate significance in predicting prognostic after surgery, whereas tumor in a thoracic level was associated with higher morbidity (p=0.021).


Microsurgery , Spinal Cord Neoplasms/surgery , Adolescent , Adult , Aged , Chi-Square Distribution , Child , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Postoperative Period , Prognosis , Spinal Cord Neoplasms/pathology
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