(Chest. 2000;117:1196-1200.)
© 2000
American College of Chest Physicians
Bilateral Diaphragm Paralysis Secondary to Central von Recklinghausen’s Disease*
Paul M. Hassoun, MD and
Bartolome R. Celli, MD, FCCP
*
From the Pulmonary and Critical Care Division, Department of Medicine (Dr. Hassoun), New England Medical Center/Tufts University School of Medicine; and the Pulmonary and Critical Care Division (Dr. Celli), St. Elizabeth’s Medical Center, Boston, MA.
Correspondence to: Paul M. Hassoun, MD, Pulmonary and Critical Care Division, Department of Medicine, New England Medical Center, 750 Washington St, NEMC 257, Boston, MA 02111; e-mail: paul.hassoun{at}es.nemc.org
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Abstract
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Bilateral paralysis of the diaphragm is either idiopathic or
associated with several medical conditions, including trauma or
thoracic surgery, viral infections, and neurologic congenital or
degenerative disorders. We describe the case of a 36-year-old man with
a history of neurofibromatosis who developed severe bilateral
diaphragmatic paralysis from involvement of the phrenic nerve roots
with neurofibromas. The patient manifested progressive
exertional dyspnea and debilitating orthopnea requiring the
use of noninvasive mechanical ventilation at night. A review of the
literature reveals that neurofibromatosis is an unrecognized cause of
diaphragmatic paralysis.
Key Words: diaphragm dysfunction • neurofibromatosis • phrenic nerve • respiratory failure
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Introduction
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While
unilateral diaphragm paralysis is of little clinical significance
unless there is underlying respiratory disease, bilateral dysfunction
of the diaphragm can cause various degrees of respiratory
dysfunction.1
In the latter case, the symptoms include
exertional dyspnea, when bilateral weakness is present, or severe
orthopnea and hypercapnic respiratory failure in bilateral diaphragm
paralysis.1
Several causes of bilateral diaphragmatic
paralysis have been described, including congenital muscular
(eg, muscular dystrophy) or neurologic (eg,
Arnold-Chiari malformation and syringomyelia) disorders; various
degenerative (eg, multiple sclerosis) and viral
(eg, herpetic) diseases; traumatic involvement of the
phrenic nerves (surgical section or thermal injury); and idiopathic
causes. However, involvement of the phrenic nerves or their roots by
neurofibromas, as described in the present case, is not a recognized
cause of bilateral diaphragm paralysis.
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Case Report
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A 36-year-old man was referred to the pulmonary clinic for
evaluation of a right upper lobe mass. His medical history was
remarkable for neurofibromatosis that had been present since age 15,
with multiple neurofibromas involving the skin and a malignant
neurofibrosarcoma that had been removed from his left leg without
complications about 15 years prior to his initial visit to our clinic.
The patient had a distant 3-pack-year smoking history and had been
abstinent for > 10 years. He had been completely asymptomatic from a
pulmonary standpoint, except for recent exertional dyspnea. A chest
roentgenogram, ordered because of right upper chest and right shoulder
discomfort, revealed a round and well-defined right apical chest mass
(Fig 1
). A chest CT scan confirmed the presence of a rounded mass measuring 5
cm in diameter and located in the right apical paravertebral region
(Fig 2
). There was no evidence of other masses along the known anatomic paths
of the phrenic nerves.2
3
The findings were compatible
with a neurofibroma, considering the patient’s known history of
neurofibromatosis. The clinical diagnosis was confirmed by surgical
resection of the tumor, which was done without complication in June of
1995. One month later, another neurofibroma was removed from the right
brachial plexus. The surgery was complicated by severe dyspnea, and
particularly orthopnea, in the postoperative period immediately
following extubation. Dyspnea improved within a few hours
postextubation; however, persistence of orthopnea after discharge from
the hospital prompted a second visit to the pulmonary clinic.
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Figure 1.. An anteroposterior chest roentgenogram revealed
the presence of a large right apical soft tissue mass, as well as an
elevated left hemidiaphragm with linear atelectasis at the left base.
The remainder of the lung parenchyma is clear.
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Figure 2.. A chest CT scan revealed the presence of a
slightly heterogeneous mass measuring 5 cm in diameter and located in
the right apical paravertebral area. There was probable thinning of the
posterior aspect of the right second rib. There was no obvious widening
of the adjacent neural foramina. The findings are nonspecific but
compatible with a neurofibroma.
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On examination, there was evidence of severe diaphragmatic dysfunction
with dullness at the bases of the lungs, diminished excursion of the
diaphragm, and marked paradoxical inward motion of the anterior
abdominal wall on deep inspiration. In addition, the patient was unable
to remain in the supine position for more than a few seconds because of
severe dyspnea. He claimed that he had been forced to sleep in an
upright position for several weeks. A workup was undertaken to confirm
the clinical suspicion of bilateral diaphragmatic paralysis. Spirometry
and lung volumes revealed a moderately severe restrictive pattern, with
FVC of 2.32 L (48% of predicted value) in the upright position and
1.51 L (31% predicted) in the supine position.
FEV1 was 1.69 L and 0.86 L in the upright and
supine positions, respectively. Maximal inspiratory and expiratory
forces were -61 (58% predicted) and +84 (42% predicted) cm
H2O pressure, respectively, confirming severe respiratory
muscle dysfunction. Transdiaphragmatic pressure, assessed by esophageal
and gastric balloon pressure monitoring, revealed a significantly
decreased pressure of 31 cm H2O. Fluoroscopic
examination of the diaphragm (the "sniff test") revealed marked
decrease in diaphragm motion bilaterally. Electromyographic studies of
the diaphragm after stimulation of the phrenic nerves on both sides
revealed no response. MRI of the cervical spine, obtained for a
complaint of arm pain and paresthesias 4 months prior to the
development of dyspnea, had revealed enlargement of the nerve roots
within and lateral to the neural foramen at the levels of C3–4 and
C6–7 on the right, and bilaterally at the levels of C4–5 and C5–6,
most consistent with multiple neurofibromas (Fig 3
). In summary, the radiographic, physiologic, and electrophysiologic
studies were all consistent with severe bilateral diaphragm paralysis,
which was believed to be secondary to involvement of the phrenic nerve
roots (C3 to C5) with neurofibromas. For the past 3 years, the patient
has been able to sleep flat at night with the assistance of noninvasive
ventilation (bilevel pressure ventilation), and exertional
dyspnea has remained stable.
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Figure 3.. MRI of the cervical spine was obtained between C2
and T1, with and without gadolinium. Top: A sagittal
T1, proton density, and T2 weighted sequences
obtained through the cervical spine is shown, revealing significant
enlargement of the neural foramina at various levels between C2–3 and
C6–7 (eg, level of C4-C5 is indicated by arrow).
Bottom: Axial T1 weighted sequences obtained
at the levels of C3–4 (left panel) and C4–5
(right panel) reveal marked enlargement of the nerve
roots, greater on the right (arrows) than on the left.
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Discussion
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Neurofibromatosis, or von Recklinghausen’s disease, is a
relatively common autosomal dominant genetic disorder in which affected
individuals develop benign and malignant tumors at an increased
frequency.4
Clinical and genetic studies have demonstrated
the existence of two distinct genetic forms of neurofibromatosis, with
mutations of genes NF1 and NF2 on chromosomes 17
and 22, respectively. While the diagnosis of these diseases is based on
clinical criteria initially established by the National Institutes of
Health Consensus Development Conference on Neurofibromatosis in
1987,5
the recent cloning of the genes NF1 and
NF2 and identification of their respective protein products,
neurofibromin and merlin or schwannomin, have significantly advanced
our understanding of these diseases and improved the diagnosis of
afflicted patients.6
The most common clinical manifestations of neurofibromatosis include
cutaneous café au lait spots and neurofibromas of the
cutaneous and subcutaneous peripheral nerves and nerve
roots.7
Thoracic neoplasms, which are not uncommon in this
disease, often arise from intercostal nerves when the patient reaches
adulthood and can be associated with some degree of rib destruction.
These tumors can project over the lungs on chest roentgenogram and,
therefore, can appear parenchymal in nature. The diagnosis of
neurofibroma or schwannoma is usually facilitated by the presence of
typical cutaneous lesions and the knowledge of long-standing von
Recklinghausen’s disease. However, surgical excision is sometimes
warranted if symptoms (eg, pain) are present or to rule out
malignant degeneration (eg, neurofibrosarcoma). Aside from
surgical resection of the tumors, there is no adequate form of therapy.
Other pulmonary manifestations of neurofibromatosis include
interstitial fibrosis with basilar predominance with or without
asymmetric bullous disease of the upper lobes.8
While involvement of the phrenic and vagus nerves by
neurofibromatosis has been occasionally described,2
3
involvement of the roots of the phrenic nerve and/or bilateral
diaphragmatic paralysis has never been reported. Nocturnal central
hypoventilation and intermittent respiratory insufficiency was
described in a patient after two surgical interventions for removal of
a recurrent cerebellopontine angle tumor.9
The respiratory
problems were thought to be directly related to extrinsic neoplastic
compression of the ventrolateral portions of the brainstem and portions
of the upper cervical cord. The patient’s condition was treated
postoperatively with implantation of bilateral phrenic nerve
pacemakers. He later developed complete failure of the right phrenic
nerve neuropacemaker that was found to be related to a neurofibroma
compressing the right phrenic nerve.9
In the present case,
involvement of the roots of the phrenic nerves with neurofibromas was
the only possible cause of bilateral diaphragmatic paralysis, as there
was no evidence of involvement of the phrenic nerves themselves by
chest CT scan. Although diaphragmatic pacing was considered for the
present case, the dramatic response of orthopnea and nocturnal
respiratory failure with the assistance of noninvasive ventilation, and
the subsequent benign clinical course convinced our patient to decline
surgery. Long-term intermittent noninvasive ventilation is effective in
reversing ventilatory failure and improving respiratory muscle
function.10
In summary, this case illustrates the possibility of severe
bilateral diaphragm paralysis due to involvement of the roots of the
phrenic nerve with neurofibromas. Noninvasive ventilation was
sufficient to improve the patient’s debilitating symptom of recumbent
respiratory insufficiency.
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Footnotes
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Supported in part by Grant RO1 HL-49411 from the National Heart, Lung,
and Blood Institute.
Received for publication August 2, 1999.
Accepted for publication September 17, 1999.
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References
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Davis, J, Goldman, M, Loh, L, et al (1976) Diaphragm function and alveolar hypoventilation. Q J Med 45,87-100[Abstract/Free Full Text]
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Bourgouin, PM, Shepard, JO, Moore, EH, et al (1988) Plexiform neurofibromatosis of the mediastinum: CT appearance. Am J Roentgenol 151,461-463[Abstract/Free Full Text]
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Lee, KS, Im, J-G, Kim, IY, et al (1991) Tumours involving the intrathoracic vagus and phrenic nerves demonstrated by computed tomography: anatomical features. Clin Radiol 44,302-305[CrossRef][ISI][Medline]
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Riccardi, VM (1981) von Recklinghausen neurofibromatosis. N Engl J Med 305,1617-1627[ISI][Medline]
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. National Institutes of Health Consensus Development Conference. (1988) Neurofibromatosis: conference statement. Arch Neurol 45,575-578[ISI][Medline]
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Gutmann, DH, Aylsworth, A, Carey, JC, et al (1997) The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 278,51-57[Abstract]
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Chan, CK, Loke, J, Virgulto, JA, et al (1988) Bilateral diaphragmatic paralysis: clinical spectrum, prognosis and diagnostic approach. Arch Phys Med Rehabil 69,976-979[ISI][Medline]
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Massaro, D, Katz, S (1966) Fibrosing alveolitis: its occurence, roentgenographic and pathologic features in von Recklinghausen’s neurofibromatosis. Am Rev Respir Dis 93,934-942[ISI][Medline]
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Richardson, RR, Johnson, N, Cerullo, LJ (1978) Diaphragm pacing in central von Recklinghausen’s disease: a case report. Neurosurgery 3,75-78[ISI][Medline]
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Celli, BR, Rassulo, J, Corral, R (1987) Ventilatory muscle dysfunction in patients with bilateral idiopathic diaphragmatic paralysis: reversal by intermittent external negative pressure ventilation. Am Rev Respir Dis 136,1276-1278[ISI][Medline]
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Abstract
Introduction
