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1.
Neurology ; 94(12): e1314-e1319, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-31992683

RESUMO

OBJECTIVE: To investigate the following among patients with phrenic neuropathy: (1) occurrences of water immersion activity-induced dyspnea; (2) clinical, electrophysiologic, sonographic, and pulmonary function test abnormalities; and (3) frequency of documented counseling regarding the risks of water immersion activities. METHODS: We identified all patients with test-confirmed phrenic neuropathy seen from January 1, 2000, to December 31, 2018, at Mayo Clinic. RESULTS: Of 535 patients with phrenic neuropathy, documentation of dyspnea with water activities was identified in 4% (22/535). The risks of water immersion were only documented in patients having experienced this problem. The majority had isolated phrenic neuritis or neuralgic amyotrophy syndrome (77.3%), mean age was 55 years (range 31-79), and most patients were men (81.9%). Patients had right-sided (45.5%) or bilateral (54.5%) phrenic neuropathy. None had isolated left phrenic involvement. Near-fatal drowning occurred in 18.2% (4/22), with persons needing assistance to be rescued from the water, following diving into water. Dyspnea with water immersion was the only symptom in 4.5% (1/22) and the presenting respiratory symptom in 36.4% (8/22). A range of electrophysiologic, sonographic, and pulmonary function test abnormalities including mild abnormalities were seen and not found to be significantly different from those in patients in whom water-induced dyspnea was not recorded. CONCLUSION: Respiratory distress with water immersion activities is a serious complication of phrenic neuropathies. Physician-documented counseling is lacking. Isolated phrenic neuritis, neuralgic amyotrophy, and right-sided and bilateral phrenic involvement are most commonly implicated, but the range of severity and testing abnormalities suggest that all patients with neuralgic amyotrophy or phrenic neuropathy should be warned especially about diving into water.


Assuntos
Dispneia/etiologia , Doenças do Sistema Nervoso Periférico/complicações , Nervo Frênico/patologia , Esportes Aquáticos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
4.
Pulmonology ; 25(4): 223-235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30509855

RESUMO

The diaphragm is the main breathing muscle and contraction of the diaphragm is vital for ventilation so any disease that interferes with diaphragmatic innervation, contractile muscle function, or mechanical coupling to the chest wall can cause diaphragm dysfunction. Diaphragm dysfunction is associated with dyspnoea, intolerance to exercise, sleep disturbances, hypersomnia, with a potential impact on survival. Diagnosis of diaphragm dysfunction is based on static and dynamic imaging tests (especially ultrasound) and pulmonary function and phrenic nerve stimulation tests. Treatment will depend on the symptoms and causes of the disease. The management of diaphragm dysfunction may include observation in asymptomatic patients with unilateral dysfunction, surgery (i.e., plication of the diaphragm), placement of a diaphragmatic pacemaker or invasive and/or non-invasive mechanical ventilation in symptomatic patients with bilateral paralysis of the diaphragm. This type of patient should be treated in experienced centres. This review aims to provide an overview of the problem, with special emphasis on the diseases that cause diaphragmatic dysfunction and the diagnostic and therapeutic procedures most commonly employed in clinical practice. The ultimate goal is to establish a standard of care for diaphragmatic dysfunction.


Assuntos
Diafragma/fisiopatologia , Nervo Frênico/fisiopatologia , Paralisia Respiratória/terapia , Ultrassonografia/métodos , Diafragma/diagnóstico por imagem , Diafragma/inervação , Diafragma/cirurgia , Eventração Diafragmática/complicações , Eventração Diafragmática/diagnóstico por imagem , Eventração Diafragmática/fisiopatologia , Fluoroscopia/métodos , Humanos , Microcirurgia/métodos , Nervo Frênico/lesões , Nervo Frênico/patologia , Nervo Frênico/cirurgia , Radiografia/métodos , Respiração Artificial/métodos , Respiração Artificial/tendências , Testes de Função Respiratória/métodos , Paralisia Respiratória/etiologia , Estimulação Elétrica Nervosa Transcutânea/métodos
5.
Respir Physiol Neurobiol ; 261: 15-23, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30590202

RESUMO

Spinal chloride-dependent synaptic inhibition is critical in regulating breathing and requires neuronal chloride gradients established by cation-chloride cotransporters Na+-K+-2Cl- (NKCC1) and K+-Cl- (KCC2). Spinal transection disrupts NKCC1/KCC2 balance, diminishing chloride gradients in neurons below injury, contributing to spasticity and chronic pain. It is not known if similar disruptions in NKCC1/KCC2 balance occur in respiratory motor neurons after incomplete cervical contusion (C2SC). We hypothesized that C2SC disrupts NKCC1/KCC2 balance in phrenic motor neurons. NKCC1 and KCC2 immunoreactivity was assessed in CtB-positive phrenic motor neurons. Five weeks post-C2SC: 1) neither membrane-bound nor cytosolic NKCC1 expression were significantly changed, although the membrane/cytosolic ratio increased, consistent with net chloride influx; and 2) both membrane and cytosolic KCC2 expression increased, although the membrane/cytosolic ratio decreased, consistent with net chloride efflux. Thus, contrary to our original hypothesis, complex shifts in NKCC1/KCC2 balance occur post-C2SC. The functional significance of these changes remains unclear.


Assuntos
Medula Cervical/lesões , Contusões/metabolismo , Neurônios Motores/metabolismo , Nervo Frênico/metabolismo , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Simportadores/metabolismo , Animais , Membrana Celular/metabolismo , Membrana Celular/patologia , Medula Cervical/metabolismo , Medula Cervical/patologia , Vértebras Cervicais , Contusões/patologia , Citosol/metabolismo , Citosol/patologia , Modelos Animais de Doenças , Masculino , Neurônios Motores/patologia , Nervo Frênico/patologia , Distribuição Aleatória , Ratos Endogâmicos Lew , Traumatismos da Medula Espinal/metabolismo
6.
J Comp Neurol ; 526(18): 2973-2983, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30411341

RESUMO

Structural plasticity in motoneurons may be influenced by activation history and motoneuron-muscle fiber interactions. The goal of this study was to examine the morphological adaptations of phrenic motoneurons following imposed motoneuron inactivity while controlling for diaphragm muscle inactivity. Well-characterized rat models were used including unilateral C2 spinal hemisection (SH; ipsilateral phrenic motoneurons and diaphragm muscle are inactive) and tetrodotoxin phrenic nerve blockade (TTX; ipsilateral diaphragm muscle is paralyzed while phrenic motoneuron activity is preserved). We hypothesized that inactivity of phrenic motoneurons would result in a decrease in motoneuron size, consistent with a homeostatic increase in excitability. Phrenic motoneurons were retrogradely labeled by ipsilateral diaphragm muscle injection of fluorescent dextrans or cholera toxin subunit B. Following 2 weeks of diaphragm muscle paralysis, morphological parameters of labeled ipsilateral phrenic motoneurons were assessed quantitatively using fluorescence confocal microscopy. Compared to controls, phrenic motoneuron somal volumes and surface areas decreased with SH, but increased with TTX. Total phrenic motoneuron surface area was unchanged by SH, but increased with TTX. Dendritic surface area was estimated from primary dendrite diameter using a power equation obtained from three-dimensional reconstructed phrenic motoneurons. Estimated dendritic surface area was not significantly different between control and SH, but increased with TTX. Similarly, TTX significantly increased total phrenic motoneuron surface area. These results suggest that ipsilateral phrenic motoneuron morphological adaptations are consistent with a normalization of motoneuron excitability following prolonged alterations in motoneuron activity. Phrenic motoneuron structural plasticity is likely more dependent on motoneuron activity (or descending input) than muscle fiber activity.


Assuntos
Neurônios Motores/patologia , Plasticidade Neuronal/fisiologia , Paralisia Respiratória/patologia , Paralisia Respiratória/fisiopatologia , Animais , Diafragma/inervação , Modelos Animais de Doenças , Nervo Frênico/patologia , Nervo Frênico/fisiopatologia , Ratos , Ratos Sprague-Dawley
7.
J Cardiothorac Surg ; 13(1): 86, 2018 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-29986737

RESUMO

BACKGROUND: Combined resection of a phrenic nerve is occasionally required in T3 primary lung carcinomas invading the phrenic nerve to completely remove a malignant tumour, resulting in diaphragmatic paralysis. We describe the first case of thoracoscopic lobectomy and diaphragmatic plication as a one-stage surgery for lung cancer invading the phrenic nerve. CASE PRESENTATION: A 56-year-old woman with a T3N0M0 primary adenosquamous carcinoma in the left upper lobe presented with suspicious invasion to the anterior mediastinal fat tissue and left phrenic nerve and underwent left upper lobectomy, node dissection, and partial resection of the anterior mediastinal fat tissue with the left phrenic nerve. Furthermore, thoracoscopic diaphragmatic plication was performed as a concomitant procedure. The patient's postoperative course was favourable, without any complications, and respiratory function was preserved for 1 year postoperatively. CONCLUSIONS: Thoracoscopic one-stage lobectomy and diaphragmatic plication for T3 lung cancer invading the phrenic nerve is effective for preservation of postoperative pulmonary function.


Assuntos
Carcinoma Adenoescamoso/cirurgia , Diafragma/cirurgia , Neoplasias Pulmonares/cirurgia , Nervo Frênico/cirurgia , Pneumonectomia/métodos , Carcinoma Adenoescamoso/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Nervo Frênico/patologia , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias , Paralisia Respiratória/prevenção & controle , Resultado do Tratamento
8.
Emerg Infect Dis ; 24(8)2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30016248

RESUMO

Since the first identification of neonatal microcephaly cases associated with congenital Zika virus infection in Brazil in 2015, a distinctive constellation of clinical features of congenital Zika syndrome has been described. Fetal brain disruption sequence is hypothesized to underlie the devastating effects of the virus on the central nervous system. However, little is known about the effects of congenital Zika virus infection on the peripheral nervous system. We describe a series of 4 cases of right unilateral diaphragmatic paralysis in infants with congenital Zika syndrome suggesting peripheral nervous system involvement and Zika virus as a unique congenital infectious cause of this finding. All the patients described also had arthrogryposis (including talipes equinovarus) and died from complications related to progressive respiratory failure.


Assuntos
Diafragma/inervação , Doenças do Sistema Nervoso Periférico/etiologia , Nervo Frênico/patologia , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/congênito , Infecção por Zika virus/complicações , Adolescente , Adulto , Feminino , Humanos , Recém-Nascido , Doenças do Sistema Nervoso Periférico/patologia , Gravidez , Adulto Jovem
9.
J Neurophysiol ; 119(5): 1852-1862, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29412773

RESUMO

Sarcopenia is the age-related reduction of muscle mass and specific force. In previous studies, we found that sarcopenia of the diaphragm muscle (DIAm) is evident by 24 mo of age in both rats and mice and is associated with selective atrophy of type IIx and IIb muscle fibers and a decrease in maximum specific force. These fiber type-specific effects of sarcopenia resemble those induced by DIAm denervation, leading us to hypothesize that sarcopenia is due to an age-related loss of phrenic motor neurons (PhMNs). To address this hypothesis, we determined the number of PhMNs in young (6 mo old) and old (24 mo old) Fischer 344 rats. Moreover, we determined age-related changes in the size of PhMNs, since larger PhMNs innervate type IIx and IIb DIAm fibers. The PhMN pool was retrogradely labeled and imaged with confocal microscopy to assess the number of PhMNs and the morphometry of PhMN soma and proximal dendrites. In older animals, there were 22% fewer PhMNs, a 19% decrease in somal surface area, and a 21% decrease in dendritic surface area compared with young Fischer 344 rats. The age-associated loss of PhMNs involved predominantly larger PhMNs. These results are consistent with an age-related denervation of larger, more fatigable DIAm motor units, which are required primarily for high-force airway clearance behaviors. NEW & NOTEWORTHY Diaphragm muscle sarcopenia in rodent models is well described in the literature; however, the relationship between sarcopenia and frank phrenic motor neuron (MN) loss is unexplored in these models. We quantify a 22% loss of phrenic MNs in old (24 mo) compared with young (6 mo) Fischer 344 rats. We also report reductions in phrenic MN somal and proximal dendritic morphology that relate to decreased MN heterogeneity in old compared with young Fischer 344 rats.


Assuntos
Envelhecimento/patologia , Medula Cervical/patologia , Diafragma/patologia , Neurônios Motores/patologia , Nervo Frênico/patologia , Sarcopenia/patologia , Animais , Feminino , Masculino , Ratos , Ratos Endogâmicos F344
10.
Exp Neurol ; 299(Pt A): 148-156, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29056361

RESUMO

In SOD1G93A transgenic rat model of ALS, breathing capacity is preserved until late in disease progression despite profound respiratory motor neuron (MN) cell death. To explore mechanisms preserving breathing capacity, we assessed inspiratory EMG activity in diaphragm and external intercostal T2 (EIC2) and T5 (EIC5) muscles in anesthetized SOD1G93A rats at disease end-stage (20% decrease in body mass). We hypothesized that despite significant phrenic motor neuron loss and decreased phrenic nerve activity, diaphragm electrical activity and trans-diaphragmatic pressure (Pdi) are maintained to sustain ventilation. We alternatively hypothesized that EIC activity is enhanced, compensating for impaired diaphragm function. Diaphragm, EIC2 and EIC5 muscle EMGs and Pdi were measured in urethane-anesthetized, spontaneously breathing female SOD1G93A rats versus wild-type littermates during normoxia (arterial PO2 ~90mmHg, PCO2 ~45mmHg), maximal chemoreceptor stimulation (MCS: 10.5% O2/7% CO2), spontaneous augmented breaths and sustained tracheal occlusion. Phrenic MNs were counted in C3-5; T2 and T5 ventrolateral MNs were counted. In end-stage SOD1G93A rats, 29% of phrenic MNs survived (vs. wild-type), yet integrated diaphragm EMG amplitude was normal. Nevertheless, maximal Pdi decreased ~30% vs. wild type (p<0.01) and increased esophageal to gastric pressure ratio (p<0.05), consistent with persistent diaphragm weakness. Despite major T2 and T5 MN death, integrated EIC2 (100% greater than wild type) and EIC5 (300%) EMG amplitudes were increased in mutant rats during normoxia (p<0.01), possibly compensating for decreased Pdi. Thus, despite significant phrenic MN loss, diaphragm EMG activity is maintained; in contrast, Pdi was not, suggesting diaphragm dysfunction. Presumably, increased EIC EMG activity compensated for persistent diaphragm weakness. These adjustments contribute to remarkable preservation of breathing ability despite major respiratory motor neuron death and diaphragm dysfunction.


Assuntos
Esclerose Amiotrófica Lateral/fisiopatologia , Diafragma/fisiopatologia , Músculos Intercostais/fisiopatologia , Músculos Respiratórios/fisiopatologia , Esclerose Amiotrófica Lateral/genética , Animais , Eletromiografia , Feminino , Neurônios Motores/patologia , Neurônios/patologia , Nervo Frênico/patologia , Nervo Frênico/fisiopatologia , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Respiração , Superóxido Dismutase-1/genética
11.
Neurorehabil Neural Repair ; 31(4): 364-375, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28332435

RESUMO

BACKGROUND: Mild intermittent hypoxia has been considered a potential approach to induce respiratory neuroplasticity. OBJECTIVE: The purpose of the present study was to investigate whether mild acute intermittent hypoxia can improve breathing function in a clinically relevant spinal cord injury animal model. METHODS: Adult male rats received laminectomy or unilateral contusion at the C3-C4 spinal cord using a MASCIS Impactor (height: 6.25 or 12.5 mm). At 4 weeks postinjury, the breathing patterns of unanesthetized rats were measured by whole body plethysmography before, during and after 10 episodes of 5 minutes of hypoxia (10% O2, 4% CO2, balance N2) with 5 minutes of normoxia intervals. RESULTS: The results demonstrated that cervical contusion resulted in reduction in breathing capacity and number of phrenic motoneurons. Acute hypoxia induced significant increases in frequency and tidal volume in sham surgery and contused animals. In addition, there was a progressive decline in the magnitude of hypoxic ventilatory response during intermittent hypoxia. Further, the tidal volume was significantly enhanced in contused but not sham surgery rats at 15 and 30 minutes postintermittent hypoxia, suggesting intermittent hypoxia can bring about long-term facilitation of tidal volume following cervical spinal contusion. CONCLUSIONS: These results suggest that mild acute intermittent hypoxia can elicit differential forms of respiratory plasticity in sham surgery versus contused animals, and may be a promising neurorehabilitation approach to improve respiratory function after cervical spinal cord injury.


Assuntos
Hipóxia/fisiopatologia , Reabilitação Neurológica , Respiração , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/reabilitação , Animais , Medula Cervical/patologia , Medula Cervical/fisiopatologia , Vértebras Cervicais , Modelos Animais de Doenças , Hipóxia/patologia , Masculino , Neurônios Motores/patologia , Neurônios Motores/fisiologia , Nitrogênio/administração & dosagem , Oxigênio/administração & dosagem , Nervo Frênico/patologia , Nervo Frênico/fisiopatologia , Pletismografia Total , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/patologia , Volume de Ventilação Pulmonar
12.
Brain Pathol ; 27(4): 459-471, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27488538

RESUMO

Motor neuron diseases such as amyotrophic lateral sclerosis (ALS) are now recognized as multi-system disorders also involving various non-motor neuronal cell types. The precise extent and mechanistic basis of non-motor neuron damage in human ALS and ALS animal models remain however unclear. To address this, we here studied progressive motor neuronopathy (pmn) mice carrying a missense loss-of-function mutation in tubulin binding cofactor E (TBCE). These mice manifest a particularly aggressive form of motor axon dying back and display a microtubule loss, similar to that induced by human ALS-linked TUBA4A mutations. Using whole nerve confocal imaging of pmn × thy1.2-YFP16 fluorescent reporter mice and electron microscopy, we demonstrate axonal discontinuities, bead-like spheroids and ovoids in pmn suralis nerves indicating prominent sensory neuropathy. The axonal alterations qualitatively resemble those in phrenic motor nerves but do not culminate in the loss of myelinated fibers. We further show that the pmn mutation decreases the level of TBCE, impedes microtubule polymerization in dorsal root ganglion (DRG) neurons and causes progressive loss of microtubules in large and small caliber suralis axons. Live imaging of axonal transport using GFP-tagged tetanus toxin C-fragment (GFP-TTC) demonstrates defects in microtubule-based transport in pmn DRG neurons, providing a potential explanation for the axonal alterations in sensory nerves. This study unravels sensory neuropathy as a pathological feature of mouse pmn, and discusses the potential contribution of cytoskeletal defects to sensory neuropathy in human motor neuron disease.


Assuntos
Transporte Axonal/genética , Microtúbulos/metabolismo , Doença dos Neurônios Motores/complicações , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/patologia , Nervo Sural/patologia , Animais , Axônios/metabolismo , Axônios/patologia , Células Cultivadas , Modelos Animais de Doenças , Embrião de Mamíferos , Gânglios Espinais/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes Neurológicos , Camundongos Transgênicos , Microtúbulos/genética , Microtúbulos/ultraestrutura , Chaperonas Moleculares/genética , Doença dos Neurônios Motores/genética , Doença dos Neurônios Motores/patologia , Mutação de Sentido Incorreto/genética , Neurônios/metabolismo , Neurônios/patologia , Neurônios/ultraestrutura , Nervo Frênico/patologia , Nervo Frênico/ultraestrutura , Polimerização , Nervo Sural/metabolismo , Nervo Sural/ultraestrutura
13.
J Neurovirol ; 23(2): 186-204, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27761801

RESUMO

Neurological respiratory deficits are serious outcomes of West Nile virus (WNV) disease. WNV patients requiring intubation have a poor prognosis. We previously reported that WNV-infected rodents also appear to have respiratory deficits when assessed by whole-body plethysmography and diaphragmatic electromyography. The purpose of this study was to determine if the nature of the respiratory deficits in WNV-infected rodents is neurological and if deficits are due to a disorder of brainstem respiratory centers, cervical spinal cord (CSC) phrenic motor neuron (PMN) circuitry, or both. We recorded phrenic nerve (PN) activity and found that in WNV-infected mice, PN amplitude is reduced, corroborating a neurological basis for respiratory deficits. These results were associated with a reduction in CSC motor neuron number. We found no dramatic deficits, however, in brainstem-mediated breathing rhythm generation or responses to hypercapnia. PN frequency and pattern parameters were normal, and all PN parameters changed appropriately upon a CO2 challenge. Histological analysis revealed generalized microglia activation, astrocyte reactivity, T cell and neutrophil infiltration, and mild histopathologic lesions in both the brainstem and CSC, but none of these were tightly correlated with PN function. Similar results in PN activity, brainstem function, motor neuron number, and histopathology were seen in WNV-infected hamsters, except that histopathologic lesions were more severe. Taken together, the results suggest that respiratory deficits in acute WNV infection are primarily due to a lower motor neuron disorder affecting PMNs and the PN rather than a brainstem disorder. Future efforts should focus on markers of neuronal dysfunction, axonal degeneration, and myelination.


Assuntos
Tronco Encefálico/imunologia , Neurônios Motores/imunologia , Nervo Frênico/imunologia , Medula Espinal/imunologia , Febre do Nilo Ocidental/imunologia , Animais , Astrócitos/imunologia , Astrócitos/patologia , Astrócitos/virologia , Tronco Encefálico/patologia , Tronco Encefálico/virologia , Contagem de Células , Cricetulus , Eletromiografia/métodos , Feminino , Humanos , Masculino , Camundongos , Microglia/imunologia , Microglia/patologia , Microglia/virologia , Neurônios Motores/patologia , Neurônios Motores/virologia , Condução Nervosa , Infiltração de Neutrófilos , Nervo Frênico/patologia , Nervo Frênico/virologia , Medula Espinal/patologia , Medula Espinal/virologia , Linfócitos T/imunologia , Linfócitos T/patologia , Linfócitos T/virologia , Febre do Nilo Ocidental/patologia , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/patogenicidade , Vírus do Nilo Ocidental/fisiologia
14.
J Neurophysiol ; 117(2): 545-555, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27832610

RESUMO

Contusion-type injuries to the spinal cord are characterized by tissue loss and disruption of spinal pathways. Midcervical spinal cord injuries impair the function of respiratory muscles and may contribute to significant respiratory complications. This study systematically assessed the impact of a 100-kDy unilateral C4 contusion injury on diaphragm muscle activity across a range of motor behaviors in rats. Chronic diaphragm electromyography (EMG) was recorded before injury and at 1 and 7 days postinjury (DPI). Histological analyses assessed the extent of perineuronal net formation, white-matter sparing, and phrenic motoneuron loss. At 7 DPI, ∼45% of phrenic motoneurons were lost ipsilaterally. Relative diaphragm root mean square (RMS) EMG activity increased bilaterally across a range of motor behaviors by 7 DPI. The increase in diaphragm RMS EMG activity was associated with an increase in neural drive (RMS value at 75 ms after the onset of diaphragm activity) and was more pronounced during higher force, nonventilatory motor behaviors. Animals in the contusion group displayed a transient decrease in respiratory rate and an increase in burst duration at 1 DPI. By 7 days, following midcervical contusion, there was significant perineuronal net formation and white-matter loss that spanned 1 mm around the injury epicenter. Taken together, these findings are consistent with increased recruitment of remaining motor units, including more fatigable, high-threshold motor units, during higher force, nonventilatory behaviors. Changes in diaphragm EMG activity following midcervical contusion injury reflect complex adaptations in neuromotor control that may increase the risk of motor-unit fatigue and compromise the ability to sustain higher force diaphragm efforts. NEW & NOTEWORTHY: The present study shows that unilateral contusion injury at C4 results in substantial loss of phrenic motoneurons but increased diaphragm muscle activity across a range of ventilatory and higher force, nonventilatory behaviors. Measures of neural drive indicate increased descending input to phrenic motoneurons that was more pronounced during higher force, nonventilatory behaviors. These findings reveal novel, complex adaptations in neuromotor control following injury, suggestive of increased recruitment of more fatigable, high-threshold motor units.


Assuntos
Contusões/complicações , Diafragma/fisiopatologia , Potencial Evocado Motor/fisiologia , Lateralidade Funcional/fisiologia , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/patologia , Análise de Variância , Animais , Vértebras Cervicais/patologia , Toxina da Cólera/metabolismo , Diafragma/patologia , Modelos Animais de Doenças , Eletromiografia , Masculino , Neurônios Motores/fisiologia , Nervo Frênico/patologia , Ratos , Ratos Sprague-Dawley
15.
Interact Cardiovasc Thorac Surg ; 23(3): 454-8, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27221999

RESUMO

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'In patients with tumours involving the phrenic nerve, does prophylactic diaphragm plication improve lung function following tumour resection?' Using the reported search, 258 papers were found of which 6 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Three case reports and one case series represent 37 patients in the literature along with two relevant animal studies. Patients treated with prophylactic plication at the time of injury or sacrifice of the phrenic nerve had reduced radiological evidence of diaphragm paralysis, lower reported shortness of breath and reduced requirement for ventilatory support. In patients with prophylactic diaphragm plication and a concurrent pulmonary resection, the predicted postoperative lung function correlated closely with the postoperative measured FEV1, FVC and gas transfer. The postoperative measured FEV1 was reported as 86-98%, the FVC 82-89% and gas transfer 97% of the predicted values. Two animal models investigate the mechanics of respiration, spirometry and gas exchange following diaphragmatic plication. A randomized control study in four dogs measured a 50% reduction in tidal volume and respiratory rate, a 40% decrease in arterial PO2 and a 43% increase in arterial CO2 when the phrenic nerve was crushed in animals with a pneumonectomy but without prophylactic diaphragm plication. A further randomized control animal study with 28 dogs found that plicating the diaphragm after unilateral phrenic nerve transection resulted in a significant increase in tidal volume and lung compliance and a significant decrease in respiratory frequency and the work of breathing. Prophylactic diaphragm plication may preserve lung function, reduce the risk of ventilator dependence and improve the mechanics of breathing in patients with phrenic nerve transection. If transection of the phrenic nerve occurs, and it is recognized intraoperatively, prophylactic diaphragm plication should be considered.


Assuntos
Diafragma/cirurgia , Pulmão/fisiopatologia , Nervo Frênico/patologia , Complicações Pós-Operatórias/prevenção & controle , Paralisia Respiratória/prevenção & controle , Timectomia , Timoma/patologia , Diafragma/inervação , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Complicações Pós-Operatórias/etiologia , Testes de Função Respiratória , Paralisia Respiratória/etiologia , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Timoma/cirurgia
16.
Crit Care ; 20: 77, 2016 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-27036885

RESUMO

BACKGROUND: Respiratory muscle weakness contributes to respiratory failure in ICU patients. Unfortunately, assessment of weakness is difficult since the most objective test, transdiaphragmatic pressure in response to phrenic nerve stimulation (PdiTw), is difficult to perform. While most clinicians utilize maximum inspiratory pressure (Pimax) to assess strength, the relationship of this index to PdiTw has not been evaluated in a large ICU population. The purpose of the present study was to assess both PdiTw and Pimax in ICU patients to determine how these indices correlate with each other, what factors influence these indices, and how well these indices predict outcomes. METHODS: Studies were performed on adult mechanically ventilated patients in the University of Kentucky MICU (n = 60). We assessed PdiTw by measuring transdiaphragmatic pressure (Pdi) in response to bilateral twitch stimulation of the phrenic nerves using dual magnetic stimulators (Magstim 200). Pimax was determined by measuring airway pressure during a 30-second inspiratory occlusion. We also assessed the twitch and maximum force generation for diaphragms excised from control and septic mice. RESULTS: Both Pimax and PdiTw measurements were profoundly reduced for mechanically ventilated MICU patients when compared to normal reference values, e.g., Pimax averaged 56% of the predicted value for normal subjects. For the ICU population as a whole, PdiTw and Pimax values correlated with each other (r(2) = 0.373, p < 0.001), but there was wide scatter and, as a result, PdiTw could not be reliably calculated from Pimax levels for individual subjects. Infection selectively reduced low-frequency force generation more than high-frequency force generation for both our mouse experiments (comparing muscle twitch to 150 Hz tetanic force) and for MICU patients (comparing PdiTw to Pimax). This effect of infection may contribute to scatter in the PdiTw to Pimax relationship. We also found that both PdiTw and Pimax were significantly correlated with both patient survival and the duration of mechanical ventilation, albeit statistically, PdiTw was the better predictor. CONCLUSIONS: While more difficult to measure, the PdiTw is a better predictor of outcomes in mechanically ventilated MICU patients than the Pimax. Nevertheless, for some clinical applications, the Pimax determination is a reasonable alternative.


Assuntos
Diafragma/fisiopatologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Ventilação com Pressão Positiva Intermitente/efeitos adversos , Adulto , Animais , Feminino , Mortalidade Hospitalar/tendências , Humanos , Unidades de Terapia Intensiva/tendências , Kentucky , Masculino , Camundongos , Modelos Animais , Debilidade Muscular/diagnóstico , Debilidade Muscular/fisiopatologia , Nervo Frênico/patologia , Pressão/efeitos adversos , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Respiração Artificial/mortalidade , Testes de Função Respiratória/estatística & dados numéricos , Músculos Respiratórios/fisiopatologia
17.
Acta Neuropathol ; 132(1): 93-110, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27021905

RESUMO

In neurons, microtubules form a dense array within axons, and the stability and function of this microtubule network is modulated by neurofilaments. Accumulation of neurofilaments has been observed in several forms of neurodegenerative diseases, but the mechanisms how elevated neurofilament levels destabilize axons are unknown so far. Here, we show that increased neurofilament expression in motor nerves of pmn mutant mice, a model of motoneuron disease, causes disturbed microtubule dynamics. The disease is caused by a point mutation in the tubulin-specific chaperone E (Tbce) gene, leading to an exchange of the most C-terminal amino acid tryptophan to glycine. As a consequence, the TBCE protein becomes instable which then results in destabilization of axonal microtubules and defects in axonal transport, in particular in motoneurons. Depletion of neurofilament increases the number and regrowth of microtubules in pmn mutant motoneurons and restores axon elongation. This effect is mediated by interaction of neurofilament with the stathmin complex. Accumulating neurofilaments associate with stathmin in axons of pmn mutant motoneurons. Depletion of neurofilament by Nefl knockout increases Stat3-stathmin interaction and stabilizes the microtubules in pmn mutant motoneurons. Consequently, counteracting enhanced neurofilament expression improves axonal maintenance and prolongs survival of pmn mutant mice. We propose that this mechanism could also be relevant for other neurodegenerative diseases in which neurofilament accumulation and loss of microtubules are prominent features.


Assuntos
Chaperonas Moleculares/metabolismo , Proteínas de Neurofilamentos/deficiência , Fator de Transcrição STAT3/metabolismo , Estatmina/metabolismo , Animais , Axônios/metabolismo , Axônios/patologia , Células Cultivadas , Estimativa de Kaplan-Meier , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Chaperonas Moleculares/genética , Atividade Motora/fisiologia , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Proteínas de Neurofilamentos/genética , Fenótipo , Nervo Frênico/metabolismo , Nervo Frênico/patologia , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia , Transdução de Sinais , Medula Espinal/metabolismo , Medula Espinal/patologia
18.
World Neurosurg ; 88: 237-242, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26746336

RESUMO

BACKGROUND: Phrenic neurofibromas are a rare pathologic entity, with 9 cases described in the English literature. They may occur in conjunction with or independently of neurofibromatosis type 1. Phrenic neurofibromas pose distinct therapeutic challenges compared with the more common phrenic schwannoma. We describe here a 12-year-old boy with neurofibroma of the left phrenic nerve presenting as dextroposition of the heart after paralysis of the left hemidiaphragm allowed herniation of abdominal contents into the left hemithorax and displaced the heart. METHOD: Surgical resection of the tumor followed by diaphragmatic plication was performed to assess its degree of malignancy, reduce abdominal herniation, and improve lung capacity. RESULTS: The operation markedly improved his hemidiaphragmatic elevation. CONCLUSIONS: The spectrum of management options ranges from conservative surveillance to open thoracic surgery. Functional preservation of the phrenic nerve is technically challenging, and although phrenic neurofibromas often present with absent function that cannot be recovered, surgical intervention can be fruitful in restoring lung capacity through diaphragmatic reconstruction.


Assuntos
Neurofibroma/diagnóstico , Neurofibroma/cirurgia , Neoplasias do Sistema Nervoso Periférico/diagnóstico , Neoplasias do Sistema Nervoso Periférico/cirurgia , Nervo Frênico/patologia , Insuficiência Respiratória/prevenção & controle , Criança , Humanos , Masculino , Neurofibroma/complicações , Procedimentos Neurocirúrgicos/métodos , Neoplasias do Sistema Nervoso Periférico/complicações , Nervo Frênico/cirurgia , Doenças Raras , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Resultado do Tratamento
19.
Clin Respir J ; 10(3): 400-3, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25103093

RESUMO

BACKGROUND AND AIMS: Isolated phrenic nerve nodule is usually a primitive tumour. Surgery is diagnostic and therapeutic at the same time. We report the case of a completely serum-negative Caucasian male with a right diaphragmatic relaxation associated to an isolated small nodule of the phrenic nerve. METHODS: The patient was referred to our unit complaining shortness of breath and progressive fatigue. A standard chest X-ray showed right diaphragmatic palsy; chest scanning revealed a nodular lesion belonging to the right phrenic nerve. Positron emission tomography was negative for glucose uptake. The preoperative diagnosis of primitive neurogenic tumour was thus supposed, and the patient treated by the lesion's surgical resection along with diaphragmatic plication. RESULT: Histopathological examination revealed an idiopathic inflammatory nodule of the phrenic nerve. CONCLUSION: Such condition has not previously been reported in the literature among the possible aetiology of a diaphragmatic relaxation.


Assuntos
Doenças do Sistema Nervoso Periférico/cirurgia , Nervo Frênico/patologia , Paralisia Respiratória/cirurgia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/diagnóstico , Nervo Frênico/cirurgia , Paralisia Respiratória/etiologia
20.
J Pediatr Surg ; 51(3): 354-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26411723

RESUMO

AIM: To evaluate the remote effect of intestinal ischemia reperfusion (IR) injury mediated by tumor necrosis factor alpha (TNF-α) on diaphragm contractility functions and whether administration of NAC may counteract the possible detrimental effects in an experimental neonatal rat model. METHODS: 40 Wistar rat pups were randomized into four groups; ten animals in each. Intestinal ischemia was conducted by obstructing mesentery of intestines by a silk loop. In the control group; only laparotomy was performed. After 1h ischemia, reperfusion was conducted for 1h in 1h group, 24h for 24h group and 24h for 24h+NAC group but administration of NAC (150mg/kg/day) intraperitoneally twice a day was performed. Inflammatory response was evaluated by tissue TNF-α level and contractility functions by mechanic activity studies of the diaphragm. Electrophysiology of the diaphragm and the phrenic nerve was conducted to determine neuropathy or myopathy and transmission electron microscopy was performed to evaluate ultrastructural changes in the phrenic nerve. RESULTS: Diaphragm tissue TNF-α level significantly increased in 1h and 24h groups (P=0.004, P=0.0001; respectively). Diaphragm mechanic activation force and duration significantly decreased at 1h and 24h (P=0.004, P=0.02 and P=0.0001, P=0.0001; respectively). NAC administration significantly prevented decrease in the maximal contraction and the duration (P<0.001). Phrenic nerve compound action potential (CMAP) amplitude significantly decreased in 1h group (P<0.0001) and NAC administration significantly prevented this decrease when compared with 24h group (P<0.001). In diaphragmatic needle electromyography, the duration of motor unit potentials (MUP) was prolonged significantly when compared with control group. Contractility and electrophysiological studies were indicating primarily neuropathy in diaphragm dysfunction. Histopathology revealed axonal and myelin degeneration in the 1h and 24h group, but less injury in the NAC administered group. CONCLUSIONS: Intestinal IR induced elevation of TNF-α level in the diaphragm. Impairment in the diaphragm contractility and neuropathic changes in the phrenic nerve occurred even in the first hour of reperfusion. NAC administration prevented these detrimental effects.


Assuntos
Acetilcisteína/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Diafragma/fisiopatologia , Intestinos/irrigação sanguínea , Contração Muscular/fisiologia , Traumatismo por Reperfusão/fisiopatologia , Acetilcisteína/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Biomarcadores/metabolismo , Diafragma/efeitos dos fármacos , Diafragma/metabolismo , Diafragma/patologia , Eletromiografia , Intestinos/patologia , Masculino , Microscopia Eletrônica de Transmissão , Contração Muscular/efeitos dos fármacos , Nervo Frênico/efeitos dos fármacos , Nervo Frênico/patologia , Nervo Frênico/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismo
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