Unilateral diaphragm paralysis: a dysfunction restricted not just to one hemidiaphragm.

BACKGROUND: Most patients with unilateral diaphragm paralysis (UDP) have unexplained dyspnea, exercise limitations, and reduction in inspiratory muscle capacity. We aimed to evaluate the generation of pressure in each hemidiaphragm separately and its contribution to overall inspiratory strength. METHODS: Twenty-seven patients, 9 in right paralysis group (RP) and 18 in left paralysis group (LP), with forced vital capacity (FVC) < 80% pred, and 20 healthy controls (CG), with forced expiratory volume in 1 s (FEV1) > 80% pred and FVC > 80% pred, were evaluated for lung function, maximal inspiratory (MIP) and expiratory (MEP) pressure measurements, diaphragm ultrasound, and transdiaphragmatic pressure during magnetic phrenic nerve stimulation (PdiTw). RESULTS: RP and LP had significant inspiratory muscle weakness compared to controls, detected by MIP (- 57.4 ± 16.9 for RP; - 67.1 ± 28.5 for LP and - 103.1 ± 30.4 cmH2O for CG) and also by PdiTW (5.7 ± 4 for RP; 4.8 ± 2.3 for LP and 15.3 ± 5.7 cmH2O for CG). The PdiTw was reduced even when the non-paralyzed hemidiaphragm was stimulated, mainly due to the low contribution of gastric pressure (around 30%), regardless of whether the paralysis was in the right or left hemidiaphragm. On the other hand, in CG, esophagic and gastric pressures had similar contribution to the overall Pdi (around 50%). Comparing both paralyzed and non-paralyzed hemidiaphragms, the mobility during quiet and deep breathing, and thickness at functional residual capacity (FRC) and total lung capacity (TLC), were significantly reduced in paralyzed hemidiaphragm. In addition, thickness fraction was extremely diminished when contrasted with the non-paralyzed hemidiaphragm. CONCLUSIONS: In symptomatic patients with UDP, global inspiratory strength is reduced not only due to weakness in the paralyzed hemidiaphragm but also to impairment in the pressure generated by the non-paralyzed hemidiaphragm.

Diaphragmatic paralysis: a rare consequence of dengue fever.

BACKGROUND: Dengue is considered one of the most common mosquito borne illnesses in the world. Although its clinical course is usually uneventful, complications have rarely been known to arise. These include neurological manifestations such as neuropathies. CASE PRESENTATION: We report a middle aged patient from urban Sri Lanka who developed diaphragmatic paralysis secondary to phrenic neuropathy a month after recovering from dengue fever. He was managed conservatively and made a full recovery subsequently. CONCLUSION: Isolated phrenic nerve palsy causing diaphragmatic paralysis should be considered a recognized complication of Dengue fever. A patient usually gains full recovery with conservative management.

Imaging of the diaphragm: anatomy and function.

The diaphragm is the primary muscle of ventilation. Dysfunction of the diaphragm is an underappreciated cause of respiratory difficulties and may be due to a wide variety of entities, including surgery, trauma, tumor, and infection. Diaphragmatic disease usually manifests as elevation at chest radiography. Functional imaging with fluoroscopy (or ultrasonography or magnetic resonance imaging) is a simple and effective method of diagnosing diaphragmatic dysfunction, which can be classified as paralysis, weakness, or eventration. Diaphragmatic paralysis is indicated by absence of orthograde excursion on quiet and deep breathing, with paradoxical motion on sniffing. Diaphragmatic weakness is indicated by reduced or delayed orthograde excursion on deep breathing, with or without paradoxical motion on sniffing. Eventration is congenital thinning of a segment of diaphragmatic muscle and manifests as focal weakness. Treatment of diaphragmatic paralysis depends on the cause of the dysfunction and the severity of the symptoms. Treatment options include plication and phrenic nerve stimulation. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.322115127/-/DC1.

Acute respiratory distress in an alpaca.

An alpaca was presented with a history of respiratory difficulty and death. Histology of the phrenic nerves and diaphragm revealed degenerative changes consistent with denervation atrophy, and a diagnosis of diaphragmatic paralysis was established. No gross or histological abnormalities were observed in the spinal cord or other organs. The etiology of the phrenic nerve neuropathy could not be determined. The need to examine phrenic nerves and diaphragm in camelids with respiratory distress is emphasized, as failure to examine these samples will preclude a diagnosis of diaphragmatic paralysis.

Doxorubicin causes diaphragm weakness in murine models of cancer chemotherapy.

Doxorubicin is a chemotherapeutic agent prescribed for a variety of tumors. While undergoing treatment, patients exhibit frequent symptoms that suggest respiratory muscle weakness. Cancer patients can receive doxorubicin chemotherapy through either intravenous (IV) or intraperitoneal (IP) injections. We hypothesized that respiratory muscle function would be depressed in a murine model of chemotherapy. We tested this hypothesis by treating C57BL/6 mice with a clinical dose of doxorubicin (20 mg/kg) via IV or IP injection. Three days later we measured contractile properties of muscle fiber bundles isolated from the diaphragm. Doxorubicin consistently depressed diaphragm force with both methods of administration (P < 0.01). Doxorubicin IP exaggerated the depression in diaphragm force and stimulated tissue inflammation and muscle fiber injury. These results suggest that clinically relevant doses of doxorubicin cause respiratory muscle weakness and that the loss of function depends, in part, on the route of administration.

Interactive effects of corticosteroid and mechanical ventilation on diaphragm muscle function.

Information on the interactive effects of methylprednisolone, controlled mechanical ventilation (CMV), and assisted mechanical ventilation (AMV) on diaphragm function is sparse. Sedated rabbits received 2 days of CMV, AMV, and spontaneous breathing (SB), with either methylprednisolone (MP; 60 mg/kg/day intravenously) or saline. There was also a control group. In vitro diaphragm force, myofibril ultrastructure, αII-spectrin proteins, insulin-like growth factor-1 (IGF-1), and muscle atrophy F-box (MAF-box) mRNA were measured. Maximal tetanic tension (P(o)) decreased significantly with CMV. Combined MP plus CMV did not decrease P(o) further. With AMV, P(o) was similar to SB and controls. Combined MP plus AMV or MP plus SB decreased P(o) substantially. Combined MP plus CMV, MP plus AMV, or MP plus SB induced myofibrillar disruption that correlated with the reduced P(o). αII-spectrin increased, IGF-1 decreased, and MAF-box mRNA increased in both the CMV group and MP plus CMV group. Short-term, high-dose MP had no additive effects on CMV-induced diaphragm dysfunction. Combined MP plus AMV impaired diaphragm function, but AMV alone did not. We found that acute, high-dose MP produces diaphragm dysfunction depending on the mode of mechanical ventilation.

Bilateral impact on the lung of hemidiaphragmatic paralysis in the dog.

The present study was designed to test the hypothesis that the expansion of a particular lung during breathing is partly related to the action of the hemidiaphragm on the opposite side. Two endotracheal tubes were inserted in the right and left main stem bronchi of anesthetized dogs, and the changes in pleural pressure (DeltaPpl) over the two lungs were assessed separately, first before and then after section of one phrenic nerve, by measuring the changes in airway opening pressure (DeltaPao) in the two tubes during occluded breaths. After phrenic nerve section, DeltaPao in the ipsilateral lung decreased 28+/-2%, and DeltaPao in the contralateral lung decreased 16+/-2% (P<0.01 for both). Parasternal intercostal activity, however, increased 15% on either side of the chest (P<0.05), thus indicating that the neural inspiratory drive was greater. Analysis of the results also suggested that after phrenic section, the contralateral (intact) hemidiaphragm still contributed nearly a third of the DeltaPpl over the ipsilateral lung. These observations indicate, in agreement with the hypothesis, that hemidiaphragmatic paralysis in the dog has a direct detrimental effect on the expansion of both lungs. They may account for the fact that in patients with hemidiaphragmatic paralysis, ventilation is reduced in both lung bases.

Long-term reorganization of respiratory pathways after partial cervical spinal cord injury.

High cervical spinal cord injury (SCI) interrupts bulbospinal respiratory pathways innervating phrenic motoneurons, and induces an inactivation of phrenic nerves (PN) and diaphragm. We have previously shown that the ipsilateral (ipsi) PN was inactivated following a lateral C2 SCI, but was spontaneously partially reactivated 7 days post-SCI. This phrenic reactivation depended on contralateral (contra) descending pathways, located laterally, that cross the spinal midline. We analysed here whether long-term post-lesional changes may occur in the respiratory network. We showed that ipsi PN reactivation was greater at 3 months compared with 7 days post-SCI, and that it was enhanced after acute contra phrenicotomy (Phx), which also induced a substantial reactivation of the ipsi diaphragm (not detected at 7 days post-SCI). At 3 months post-SCI (compared with 7 days post-SCI), ipsi PN activity was only moderately affected by ipsi Phx or by gallamine treatment, a nicotinic neuromuscular blocking agent, indicating that it was less dependent on ipsi sensory phrenic afferents. After an additional acute contra SCI (C1) performed laterally, ipsi PN activity was abolished in rats 7 days post-SCI, but persisted in rats 3 months post-SCI. This activity thus depended on new functional descending pathways located medially rather than laterally. These may not involve newly recruited neurons as retrograde labelling showed that ipsi phrenic motoneurons were innervated by a similar number of medullary respiratory neurons after a short and long post-lesional time. These results show that after a long post-lesional time, phrenic reactivation is reinforced by an anatomo-functional reorganization of spinal respiratory pathways.

Unilateral diaphragm paralysis: etiology, impact, and natural history.

AIM: The etiology, clinical impact, natural history and best therapy of unilateral diaphragm paralysis (UDP) are incompletely understood. This condition is not amenable to pacing, which requires an intact phrenic nerve. METHODS: Clinical records of patients with UDP referred to our diaphragm center were reviewed. RESULTS: Thirty-six patients (28 male, 8 female) aged 1 month to 78 years (mean 47.8 years) with UDP evaluated from 1983 to February 2007 were reviewed. Etiology was postsurgical in 13 (36%), tumor (with surgery or radiation therapy) in 7 (19%), idiopathic in 6 (17%), trauma (motor vehicle accident or head injury) in 5 (14%), polio in 3 (8%), and viral in 2 (6%) patients. 28 patients (78%) were symptomatic; 8 (22%) carried a diagnosis of coexisting chronic obstructive pulmonary disease. Mean duration of paralysis was 57.9 months (range up to 261 months). The left diaphragm was involved in 23 cases (64%) and the right in 13 (36%). Mean forced expiratory volume (FEV1) was 1 915 mL (61.3% of predicted) and mean forced vital capacity (FVC) was 2 432 mL (62.9% of predicted). Mean pO2 was 69.9 mmHg (range 49 to 124), indicating considerable shunting through underventilated lung. Pulmonary infection affected 3 patients (8.4%). Diaphragm function returned in 17% of patients (mainly children) at mean of 10.3 months. Four incapacitated patients (11 %) were treated surgically, with resection of the hemi-diaphragm. Surgical exploration revealed neurogenic atrophy of the diaphragm muscle. All 4 resected patients showed clinical, oxymetric, and spirometric improvement. CONCLUSION: The conclusion is drawn that: 1) UDP may be traumatic, tumor-related, iatrogenic, or idiopathic; 2) UDP decreases pO(2) substantially and breathing capacity by more than 1/3; 3) spontaneous recovery is possible; 4) UDP is not intrinsically lethal; 5) occasional patients are incapacited; 6) diaphragm resection produces clinical improvement via lower lobe re-expansion; 7) the incapacity incurred by UDP is mild compared to the clinical spectrum of bilateral diaphragm paralysis.

Neuromuscular disease and respiratory failure.

Neurologists should be able to anticipate and recognise the onset of respiratory failure in patients with neuromuscular disorders. Symptoms will differ depending on the speed of onset of the respiratory muscle weakness. Careful monitoring of respiratory function is particularly important in acute disorders such as Guillain-Barré syndrome. Patients with an unrecognised neuromuscular disorder may occasionally present with respiratory failure. Important investigations include vital capacity, mouth pressures, arterial blood gases, chest x ray and sometimes overnight respiratory monitoring. Patients with Guillain-Barré and other acute conditions may require short-term ventilatory support in the intensive care unit. Patients with some chronic disorders, such as motor neuron disease and Duchenne dystrophy, can be successfully treated with non-invasive ventilation, usually in collaboration with a respiratory physician. New-onset weakness of limb and respiratory muscles in the intensive care unit is usually due to critical illness myopathy or critical illness polyneuropathy, and treatment is supportive.

Phrenic motoneuron structural plasticity across models of diaphragm muscle paralysis.

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.

Diaphragmatic thickness ratio (inspiratory/expiratory) as a diagnostic method of diaphragmatic palsy associated with interescalene block. / La ratio de grosor diafragmático (inspiratorio/espiratorio) como método diagnóstico de parálisis diafragmática asociada al bloqueo interescálenico.

INTRODUCTION: Diaphragmatic paralysis is a side-effect associated with interscalene block. Thickness index of the diaphragm muscle (inspiratory thickness/expiratory thickness) obtained by ultrasound has recently been introduced in clinical practice for diagnosis of diaphragm muscle atrophy. Our objective was to evaluate this index for the diagnosis of acute phrenic paresis associated with interscalene block. PATIENTS AND METHODS: We designed an observational study in 22 patients scheduled for shoulder arthroscopy. Spirometry was performed (criteria of phrenic paresis was a decrease in FVC and FEV1 ≥20%). Ultrasound apposition zone was assessed in anterior axillary line and diaphragmatic displacement was evaluated on inspiration and expiration (number of intercostal spaces; phrenic paresis considered a reduction ≥25%) and thickness of the diaphragm muscle (a phrenic paresis was considered an index <1.2). These determinations were performed before and at 20min after interscalene block at C5-C6 with 20ml of 0.5% ropivacaine. RESULTS: Twenty-one patients (95%) presented phrenic nerve block according to one or more of the methods used. One patient did not show any symptoms or signs suggestive of phrenic paralysis and was excluded. All the patients presented phrenic paresis based on the diaphragmatic thickness index, with the pre-block index being 1.8±0.5 and post-block of 1.05±0.06 (P<0.001). Ninety percent of the patients (19) presented phrenic paresis according to spirometry and all the patients had a reduction in diaphragmatic movement after the block (from 1.9±0.5 intercostal spaces to 0.5±0.3; P<0.001). CONCLUSION: The index of inspiratory / expiratory diaphragmatic thickness at cut-off <1.2 seems to be useful in the diagnosis of phrenic paresis associated with interscalene block. This index does not require a baseline pre-assessment.

Diagnosis of myotubular myopathy in the oldest known manifesting female carrier: a clinical and genetic study.

X-linked myotubular myopathy is a congenital myopathy due to mutation in the MTM1 gene, encoding myotubularin. Most of the affected male neonates die early of respiratory failure. The female carriers are usually asymptomatic. The authors report a novel MTM1 mutation in a 77-year-old woman. She presented with progressive ptosis since childhood, proximal limb weakness, and a severe restrictive respiratory dysfunction with a hemidiaphragmatic paresis, leading to death at 84 years of age. The muscle biopsy showed centrally nucleated fibers and mitochondrial abnormalities. A stop mutation Leu498X in MTM1 gene was identified in the proband and in her two healthy daughters. The X-inactivation pattern was random in the proband's blood and muscle DNA, and in blood DNA from her two unaffected MTM1 mutation carrier daughters. Two large heteroplasmic deletions were also detected in the muscle mitochondrial DNA of the propositus, raising the question of their putative impact on the phenotype.

Compensatory effects following unilateral diaphragm paralysis.

Injury to nerves innervating respiratory muscles such as the diaphragm muscle results in significant respiratory compromise. Electromyography (EMG) and transdiaphragmatic pressure (Pdi) measurements reflect diaphragm activation and force generation. Immediately after unilateral diaphragm denervation (DNV), ventilatory behaviors can be accomplished without impairment, but Pdi generated during higher force non-ventilatory behaviors is significantly decreased. We hypothesized that 1) the initial reduction in Pdi during higher force behaviors after DNV is ameliorated after 14 days, and 2) changes in Pdi over time after DNV are associated with concordant changes in contralateral diaphragm EMG activity and ventilatory parameters. In adult male rats, the reduced Pdi during occlusion (∼40% immediately after DNV) was ameliorated to ∼20% reduction after 14 days. Contralateral diaphragm EMG activity did not significantly change immediately or 14days after DNV compared to the pre-injury baseline for any motor behavior. Taken together, these results suggest that over time after DNV compensatory changes in inspiratory related muscle activation may partially restore the ability to generate Pdi during higher force behaviors.

Crus Atrophy: Accuracy of Computed Tomography in Diagnosis of Diaphragmatic Paralysis.

PURPOSE: The aim of this study was to measure the association between crus atrophy as depicted by computed tomography (CT) and fluoroscopic diagnosis of hemidiaphragmatic paralysis in patients with suspected diaphragmatic dysfunction. MATERIALS AND METHODS: A retrospective review of patient data was approved by our institutional review board and was HIPPA-compliant. We reviewed 90 patients who had undergone diaphragmatic fluoroscopy; 72 had CT scans available for measurement of crus thickness at the levels of the celiac and superior mesenteric arteries and the L1 vertebral body. Receiver operating characteristic analysis was used to determine the threshold of crus thinning that best distinguished a paralyzed hemidiaphragm from a nonparalyzed one. RESULTS: Hemidiaphragmatic paralysis caused significant crus thinning at the celiac artery level (mean±SD, 1.7±0.6 vs. 3.6±1.3 mm, P=0.017, on the right; 1.1±0.4 vs. 3.0±1.4 mm, P=0.001, on the left) and the L1 vertebral level (mean±SD, 1.5±0.7 vs. 4.4±1.6 mm, P=0.018, on the right; 1.5±0.6 vs. 3.6+1.7 mm, P=0.017, on the left). On axial CT, thinning to ≤2.5 mm at the celiac artery level identified paralysis of the hemidiaphragm with a sensitivity of 100% and a specificity of 86% on the right and with a sensitivity of 100% and a specificity of 64% on the left. On coronal CT, thinning to ≤2.5 mm at the L1 vertebral level identified paralysis of the hemidiaphragm with a sensitivity of 100% and a specificity of 88% on the right and with a sensitivity of 100% and a specificity of 77% on the left. CONCLUSIONS: Atrophy of the crus assessed by CT is a good discriminator of paralyzed versus nonparalyzed hemidiaphragm in patients with suspected diaphragmatic dysfunction.

Co-existince of sickle cell disease and hemidiaphragm paralysis.

Sickle cell anemia is a disease caused by production of abnormal hemoglobin. Infection, acute splenic sequestration crisis, aplastic crises, acute chest syndrome, stroke, cholelithiasis, renal disease and pain are the major complications. Unilateral or bilateral diaphragm paralysis maybe seen following phrenic nerve injury and with a variety of motor-neuron diseases, myelopathies, neuropathies, and myopathies. Prominent right hemi-diaphragma elevation was observed on chest radiograph of a 14 years' old female patient with sickle cell disease. Her medical history yielded neither trauma nor intra-thoracic surgery. She didn't have either motor deficit or sensation disorder on any region of her body. Thorax CT yielded no lesion except the significantly elevated right diaphragm. Her cranial CT showed no lesion, too. Diagnosis of right hemidiaphragm paralysis was confirmed by positive Hitzenberg Sniff test on fluoroscopy. Although several pathophysiologic mechanisms are known to be involved and lead to central neurologic complications in sickle cell disease, involvement of peripheric nerves have not been reported. Here we present a 14 years' old female patient with sickle cell anemia and unilateral diaphragm paralysis, co-existence of which have not been reported so far.

[Bilateral diaphragmatic paralysis due to Parsonage-Turner syndrome]. / Une paralysie diaphragmatique révélatrice d'un syndrome de Parsonage-Turner.

We report the case of a 49-years-old patient who presented to the accident and emergency department with sudden onset dyspnea associated with acute shoulder pain. He was breathless at rest with supine hypoxemia. He had an amyotrophic left shoulder with localized paresis of the shoulder. Both hemi-diaphragms were elevated on chest X-rays. Pulmonary function tests showed a restrictive pattern and both phrenic nerve conduction velocities were decreased. At night, alveolar hypoventilation was evidenced by elevated mean capnography (PtcCO2: 57mmHg). Neuralgic amyotrophy, Parsonage-Turner syndrome was the final diagnosis. This syndrome is a brachial plexus neuritis with a predilection for the suprascapular and axillary nerves. Phrenic nerve involvement is rare but where present can be the most prominent clinical feature as in our case report.

Patient with spinal muscular atrophy with respiratory distress type 1 presenting initially with hypertonia.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive neuromuscular disorder caused by mutations in the IGHMBP2 gene and characterized by life-threatening respiratory distress due to irreversible diaphragmatic paralysis between 6weeks and 6months of age. In this study, we describe a two-month-old boy who presented with hypertonia at first and developed to hypotonia progressively, which was in contrast to the manifestations reported previously. Bone tissue compromise was also observed as one of the unique symptoms. Muscle biopsy indicated mild myogenic changes. He was misdiagnosed until genetic screening to be confirmed as SMARD1. SMARD1 is a clinical heterogeneous disease and this case broadens our perception of its phenotypes.