ltal. J. Neurol. Sci. 13:435 438, 1992
Neurogenic pulmonary edema: a presenting symptom in multiple sclerosis Gentiloni N.*, Schiavino D.*, Della Corte F.**, Ricci E.***, Colosimo C.**** Universitfl Cattolica del Sacro Cuore, Policlinico A. Gemelli, R o m a * Istituto di Clinica M e d i c a ** Istituto di Anestesia e R i a n i m a z i o n e *** lstituto di Neurologia **** Istituto di Radiologia
Altered cardiovascular and respiratory function is uncommonly encountered in multiple sclerosis, though it may appear late in the course of the disease [4]. Episodes of acute ventilatory failure due to autonomic and~or voluntary respiratory function paralysis have already been described. These episodes are often accompanied by a focal neurological deficit which expresses lesion at the level of the medulla [6]. A demyelinating bulbar lesion leading to altered cardiovascular function is likewise infrequent but when it happens, bradycardia, postural hypotension [2], or acute pulmonary edema without heart failure may occur [11. We present a case of non cardiogenic acute pulmonary edema which had neither a toxic insult nor an infective agent as etiology, but appeared as the initial manifestation of a multifocal demyelinating syndrome.
Key Words: Multiple sclerosis - - neurogenic pulmonary edema
Case Report A conscious 16 years old girl presented to the emergency department in a collapsed state with a blood pressure of 70/50 mmHg, after a sleepless night with headache, profuse sweating and repeated vomiting. Two weeks earlier, while the patient was taking her driving test, she had experienced some difficulties in writing and verbal expression, which her family and her doctor attributed to stress. While under our observation, the patient continued to vomit small quantities of coffee ground-like substance, but had no abdominal complaints. Temperature was normal, chest examination was unremarkable and auscultation of the heart reReceived 13 March 1991 - Accepted 30 August 1991
vealed a third heart sound. Abdomen was soft, non tender with normal bowel sounds. Neurological examination showed rotary nystagmus and normal sensation and motor function of the limbs. Electrocardiogram demonstrated alterations compatible with increased sympathetic tone with a heart rate of 120 per minute. Apart from a leukocytosis of 21,000/mm 3 with a left shift, the biochemical studies including serum amylase levels were normal. After some hours on intravenous fluid support therapy and while waiting to undergo endoscopic examination of the upper gastrointestinal tract, the patient suddenly went into acute pulmonary edema. Radiographic findings were typical of the disorder (Fig. l) and her arterial blood gas analysis 435
The Italian Journal of Neurological Sciences
Fig. 1. Chest X-ray demonstrates lmhnonary edeIlla.
anti-DNA antibodies and circulating immunocomplexes were absent; complement and immunoglobulins were normal. Finally, there were no symptoms of kidney, heart, joint, skin or peripheral nervous system involvement. A few days after the start of prednisone 100 mg/ Kg/day, the patient showed substantial improvement with resolution of the neurological symptoms. On the fifth day, however, the serum amylase and serum lipase rose to as much as 1,265 u/ I and 1,047 u/I respectively (90% of the amylase was pancreatic in origin). The patient had no abdominal pain. Ultrasonographic study revealed no alterations of the pancreas. The patient was discharged from the hospital one month after admission complaining only of nocturnal sharp burning pains in the legs. During the subsequent 12 months the disease showed a typical relapsing and remitting course: the patient was readmitted twice because of acute onset cerebellar ataxia. On both occasions she was given high doses of prednisone and recovered in a few weeks. Discussion
displayed pH of 7.634, PaCO2 of 23.4 mmHg and PaO2 of 41.9 mmHg. The patient was immediately transferred to the intensive care unit, where ventilatory support with continuous positive airway pressure (CPAP) through a face mask was promptly commenced at a pressure of 10 cmH20. The hemodynamics of the pulmonary circulation measured with a Swan-Ganz catheter was normal. Echocardiography demonstrated normal-sized cardiac chambers and conserved kinetics. The positive pressure ventilation resulted in rapid improvement of respiratory symptoms, and within 12 hours of support treatment, PaO, increased to 105 mmHg with a fractional oxygen concentration of inspired air of 1 (FIOD. Over a period of 24 hours, other signs of brainstem damage became evident. Besides the rotary nystagmus already noted, dysphonia and unilateral paresis of the soft palate and the tongue appeared. CT scan showed a large low density area with irregular margins corresponding to the white matter of the corona radiata and the medullary center. This lesion, suspicious for a demyelinating process, corresponded with findings on MRI which in addition showed numerous small scattered lesions in the white matter of both hemispheres, the posterior limb of the internal capsule on the left, the right cerebellar hemisphere and the right paramedian region of the medulla dorsally (Fig. 2). CSF studies showed the presence of oligoclonal banding of IgG with a normal IgG to albumin ratio. Other CSF parameters were normal and immunological and serological studies for neurotropic viruses were negative; the erythrocyte sedimentation rate was normal; antinuclear and 436
The diagnosis of multiple sclerosis in our case is in accordance with criteria established in 1986 by Sander, Bellen and Van Der Velde. The subtle disturbance of writing and wording that was the first symptom was quickly followed by a dysautonomic syndrome (headache, hyperhidrosis, vomiting and hypotension) and later by a bulbar syndrome. The latter was associated with acute pulmonary edema for which no cardiac, toxic or infective etiology was found. It was therefore diagnosed as neurogenic [5]. MRI revealed the presence of multiple non contiguous lesions consistent with demyelinating plaques within the white matter of both hemispheres, medulla and cerebellum. CSF was positive for oligoclonal bands. The disease showed a relapsing and remitting course. We found no clinical or laboratory evidence of systemic vasculitis. Given the young age, absence of headache, the CT and MRI features and presence of oligoclonal bands on CFS examination, an isolated angiitis of the central nervous system, a rare event, was unlikely. An elevated serum pancreatic enzymes may suggest a differential diagnosis of demyelinating leukoencephalopathy in the course of acute pancreatitis; but, a part from other considerations, the phenomenon that was probably an expression of pancreatic derangement associated with the patient's collapsed and hypoxic state manifested itself on the fifth day when the neurological symptoms were in regression. The peculiarity of this case lies in the initial manifestation of the disease: a bulbar syndrome presenting as non- cardiogenic pulmonary edema.
Gentiloni N.: Neurogenic pulmonal 3 edema in M.S.
A
B
/,
C
D
Fig. 2. MRI of the brain discloses multiple leukoencephalopathic demyelinating areas consistent with: multiple sclerosis. A,B. A hyperintense lesion (arrowheads) is seen in the right medulla O' tegmentum. C,D. Multiple h3perintense lesions (large arrows) are demonstrated in the white matter o f the left hemisphere; the largest one abuts 077 the centrum semiovaIe in the body o f the corpus callosum (small arrows).
Apart from the multiple supratentorial and cere- 9 in Japanese and western studies with a higher frebellar demyelinating lesions, MRI showed a plaquency in Japanese patients [3]. que on the dorsal paramedial region of the medNeurogenic pulmonary edema as a starting sympulla. The incidence of medullary lesions in multom in this disease is really exceptional. The motiple sclerosis is estimated at between 4% and 9%; re commonly seen neurogenic pulmonary edema however, the occurrence of respiratory and cardiis a frequent complication of intracranial patholocirculatory alterations is far below what one ogies (cranial trauma, intracerebral hemorrhage, would expect. Paralysis of autonomic and/or v o l status epilepticus etc.) and is characterized by untary functions of respiration has been described severe symptoms from the outset and a poor 437
The Italian Journal of Neurologit'al Sciences
prognosis. According to some authors, the pathophysiological basis for this is an absolute variation in intracranial pressure and dysfunction of the hypothalamus that results in the release of a large amount of catecholamines, and hence severe repercussions on the cardiovascular system. In the absence of increased intracranial pressure, the likely cause of neurogenic pulmonary edema from a demyelinating bulbar lesion is damage to the dorsal motor nuclei of the vagus and median reticular nucleus which control respiratory and cardiac functions. Describing a case similar to ours [1], M. Giroud states that in the experimental an-
imai, bilateral lesion of the dorsal nucleus of the vagus causes acute pulmonary edema with increase in pulmonary capillary but not systemic hydrostatic pressure and without accompanying heart failure. In our case cardiac function and pulmonary and systemic hydrostatic pressure were normal. Since no fluid sample from the bronchoalveolar aspirate was obtained, we were unable to determine the alveolar fluid/plasma protein ratio. Therefore, a sudden increase in pulmonary capillary endothelial permeability as a pathogenetic mechanism remains a plausible but as yet unproven hypothesis.
Sommario I disturbi cardio-vascolari e respiratori sono piuttosto rari nella sclerosi multipla, anche se possono comparire nella f a s e terminale della malattia. Sono stati descritti episodi di deficit acuto nella ventilazione polmonare; questi episodi sono spesso accompagnati da deficit neurologici focali, che sono espressione di localizzazioni della malattia a livello del bulbo. Lesioni bulbari demielinizzanti in grado di alterare la funzione cardiovascolare sono rare, ma quando si verificano esse possono indurre bradicardia, ipotensione ortostatica o edema polmonare acuto senza deficit della funzione cardiaca. Noi presentiamo un caso di edema polmonare acuto non cardiogeno, non tossico e non infettivo, ma che appare come la manifestazione iniziale di una sindrome demlelmtzzante multifocale.
Address reprint requests to: Prof. Nicola Gentiloni Istituto di Clinica Medica, Policlinico A. Gemelli, Largo A. Gemelli, 1, 00168 Roma.
References [1] G1ROUDM., GUARDO., DUMASR.: Anomalies cardio-respiratoires dans la scl~rose en plaques. Rev. Neurol. (Paris) 144, 4, 284-88, 1988. [2] NORONHAM.J., VAS C.J., AZlZH.: Autonomic dysfunction in muln'ple sclerosis. J. Neurol. Neurosurg, Psychiatry, 31:19-22, 1968. [3] OCHIAIY., YOKOJAMAM., KOSOKABEY., ABE S., TANIGUCHIM., TADA K." Intensive care of multiple sclerosis with bulbar palsy. J. Intensive Care
438
Med. (Tokyo) _5:579-86, 1981. [4] STEFOSKID., Davis F.A.: Central disturbances of respiration in multiple sclerosis. In: W.J. Weiner (Ed.), Respiratory dysfunction in neurologic disease. Futura Mount Kisco NY pag. 187-196, 1980. [5] THEODOREJ., ROBINE.D.: Speculations on neurogenic pulmonary edema. Ann. Rev. Respir. Dis., 113:405-11, 1976. [61 TORN YAMAMOTO, TERUKUNI IMAI, MASAHIRO YAMASAKI: Acute ventilator3, f a i l u r e in multiple
sclerosis. J. Neurol. Sci., 89:313-24, 1989.
Neurogenic pulmonary edema: a presenting symptom in multiple sclerosis Gentiloni N.*, Schiavino D.*, Della Corte F.**, Ricci E.***, Colosimo C.**** Universitfl Cattolica del Sacro Cuore, Policlinico A. Gemelli, R o m a * Istituto di Clinica M e d i c a ** Istituto di Anestesia e R i a n i m a z i o n e *** lstituto di Neurologia **** Istituto di Radiologia
Altered cardiovascular and respiratory function is uncommonly encountered in multiple sclerosis, though it may appear late in the course of the disease [4]. Episodes of acute ventilatory failure due to autonomic and~or voluntary respiratory function paralysis have already been described. These episodes are often accompanied by a focal neurological deficit which expresses lesion at the level of the medulla [6]. A demyelinating bulbar lesion leading to altered cardiovascular function is likewise infrequent but when it happens, bradycardia, postural hypotension [2], or acute pulmonary edema without heart failure may occur [11. We present a case of non cardiogenic acute pulmonary edema which had neither a toxic insult nor an infective agent as etiology, but appeared as the initial manifestation of a multifocal demyelinating syndrome.
Key Words: Multiple sclerosis - - neurogenic pulmonary edema
Case Report A conscious 16 years old girl presented to the emergency department in a collapsed state with a blood pressure of 70/50 mmHg, after a sleepless night with headache, profuse sweating and repeated vomiting. Two weeks earlier, while the patient was taking her driving test, she had experienced some difficulties in writing and verbal expression, which her family and her doctor attributed to stress. While under our observation, the patient continued to vomit small quantities of coffee ground-like substance, but had no abdominal complaints. Temperature was normal, chest examination was unremarkable and auscultation of the heart reReceived 13 March 1991 - Accepted 30 August 1991
vealed a third heart sound. Abdomen was soft, non tender with normal bowel sounds. Neurological examination showed rotary nystagmus and normal sensation and motor function of the limbs. Electrocardiogram demonstrated alterations compatible with increased sympathetic tone with a heart rate of 120 per minute. Apart from a leukocytosis of 21,000/mm 3 with a left shift, the biochemical studies including serum amylase levels were normal. After some hours on intravenous fluid support therapy and while waiting to undergo endoscopic examination of the upper gastrointestinal tract, the patient suddenly went into acute pulmonary edema. Radiographic findings were typical of the disorder (Fig. l) and her arterial blood gas analysis 435
The Italian Journal of Neurological Sciences
Fig. 1. Chest X-ray demonstrates lmhnonary edeIlla.
anti-DNA antibodies and circulating immunocomplexes were absent; complement and immunoglobulins were normal. Finally, there were no symptoms of kidney, heart, joint, skin or peripheral nervous system involvement. A few days after the start of prednisone 100 mg/ Kg/day, the patient showed substantial improvement with resolution of the neurological symptoms. On the fifth day, however, the serum amylase and serum lipase rose to as much as 1,265 u/ I and 1,047 u/I respectively (90% of the amylase was pancreatic in origin). The patient had no abdominal pain. Ultrasonographic study revealed no alterations of the pancreas. The patient was discharged from the hospital one month after admission complaining only of nocturnal sharp burning pains in the legs. During the subsequent 12 months the disease showed a typical relapsing and remitting course: the patient was readmitted twice because of acute onset cerebellar ataxia. On both occasions she was given high doses of prednisone and recovered in a few weeks. Discussion
displayed pH of 7.634, PaCO2 of 23.4 mmHg and PaO2 of 41.9 mmHg. The patient was immediately transferred to the intensive care unit, where ventilatory support with continuous positive airway pressure (CPAP) through a face mask was promptly commenced at a pressure of 10 cmH20. The hemodynamics of the pulmonary circulation measured with a Swan-Ganz catheter was normal. Echocardiography demonstrated normal-sized cardiac chambers and conserved kinetics. The positive pressure ventilation resulted in rapid improvement of respiratory symptoms, and within 12 hours of support treatment, PaO, increased to 105 mmHg with a fractional oxygen concentration of inspired air of 1 (FIOD. Over a period of 24 hours, other signs of brainstem damage became evident. Besides the rotary nystagmus already noted, dysphonia and unilateral paresis of the soft palate and the tongue appeared. CT scan showed a large low density area with irregular margins corresponding to the white matter of the corona radiata and the medullary center. This lesion, suspicious for a demyelinating process, corresponded with findings on MRI which in addition showed numerous small scattered lesions in the white matter of both hemispheres, the posterior limb of the internal capsule on the left, the right cerebellar hemisphere and the right paramedian region of the medulla dorsally (Fig. 2). CSF studies showed the presence of oligoclonal banding of IgG with a normal IgG to albumin ratio. Other CSF parameters were normal and immunological and serological studies for neurotropic viruses were negative; the erythrocyte sedimentation rate was normal; antinuclear and 436
The diagnosis of multiple sclerosis in our case is in accordance with criteria established in 1986 by Sander, Bellen and Van Der Velde. The subtle disturbance of writing and wording that was the first symptom was quickly followed by a dysautonomic syndrome (headache, hyperhidrosis, vomiting and hypotension) and later by a bulbar syndrome. The latter was associated with acute pulmonary edema for which no cardiac, toxic or infective etiology was found. It was therefore diagnosed as neurogenic [5]. MRI revealed the presence of multiple non contiguous lesions consistent with demyelinating plaques within the white matter of both hemispheres, medulla and cerebellum. CSF was positive for oligoclonal bands. The disease showed a relapsing and remitting course. We found no clinical or laboratory evidence of systemic vasculitis. Given the young age, absence of headache, the CT and MRI features and presence of oligoclonal bands on CFS examination, an isolated angiitis of the central nervous system, a rare event, was unlikely. An elevated serum pancreatic enzymes may suggest a differential diagnosis of demyelinating leukoencephalopathy in the course of acute pancreatitis; but, a part from other considerations, the phenomenon that was probably an expression of pancreatic derangement associated with the patient's collapsed and hypoxic state manifested itself on the fifth day when the neurological symptoms were in regression. The peculiarity of this case lies in the initial manifestation of the disease: a bulbar syndrome presenting as non- cardiogenic pulmonary edema.
Gentiloni N.: Neurogenic pulmonal 3 edema in M.S.
A
B
/,
C
D
Fig. 2. MRI of the brain discloses multiple leukoencephalopathic demyelinating areas consistent with: multiple sclerosis. A,B. A hyperintense lesion (arrowheads) is seen in the right medulla O' tegmentum. C,D. Multiple h3perintense lesions (large arrows) are demonstrated in the white matter o f the left hemisphere; the largest one abuts 077 the centrum semiovaIe in the body o f the corpus callosum (small arrows).
Apart from the multiple supratentorial and cere- 9 in Japanese and western studies with a higher frebellar demyelinating lesions, MRI showed a plaquency in Japanese patients [3]. que on the dorsal paramedial region of the medNeurogenic pulmonary edema as a starting sympulla. The incidence of medullary lesions in multom in this disease is really exceptional. The motiple sclerosis is estimated at between 4% and 9%; re commonly seen neurogenic pulmonary edema however, the occurrence of respiratory and cardiis a frequent complication of intracranial patholocirculatory alterations is far below what one ogies (cranial trauma, intracerebral hemorrhage, would expect. Paralysis of autonomic and/or v o l status epilepticus etc.) and is characterized by untary functions of respiration has been described severe symptoms from the outset and a poor 437
The Italian Journal of Neurologit'al Sciences
prognosis. According to some authors, the pathophysiological basis for this is an absolute variation in intracranial pressure and dysfunction of the hypothalamus that results in the release of a large amount of catecholamines, and hence severe repercussions on the cardiovascular system. In the absence of increased intracranial pressure, the likely cause of neurogenic pulmonary edema from a demyelinating bulbar lesion is damage to the dorsal motor nuclei of the vagus and median reticular nucleus which control respiratory and cardiac functions. Describing a case similar to ours [1], M. Giroud states that in the experimental an-
imai, bilateral lesion of the dorsal nucleus of the vagus causes acute pulmonary edema with increase in pulmonary capillary but not systemic hydrostatic pressure and without accompanying heart failure. In our case cardiac function and pulmonary and systemic hydrostatic pressure were normal. Since no fluid sample from the bronchoalveolar aspirate was obtained, we were unable to determine the alveolar fluid/plasma protein ratio. Therefore, a sudden increase in pulmonary capillary endothelial permeability as a pathogenetic mechanism remains a plausible but as yet unproven hypothesis.
Sommario I disturbi cardio-vascolari e respiratori sono piuttosto rari nella sclerosi multipla, anche se possono comparire nella f a s e terminale della malattia. Sono stati descritti episodi di deficit acuto nella ventilazione polmonare; questi episodi sono spesso accompagnati da deficit neurologici focali, che sono espressione di localizzazioni della malattia a livello del bulbo. Lesioni bulbari demielinizzanti in grado di alterare la funzione cardiovascolare sono rare, ma quando si verificano esse possono indurre bradicardia, ipotensione ortostatica o edema polmonare acuto senza deficit della funzione cardiaca. Noi presentiamo un caso di edema polmonare acuto non cardiogeno, non tossico e non infettivo, ma che appare come la manifestazione iniziale di una sindrome demlelmtzzante multifocale.
Address reprint requests to: Prof. Nicola Gentiloni Istituto di Clinica Medica, Policlinico A. Gemelli, Largo A. Gemelli, 1, 00168 Roma.
References [1] G1ROUDM., GUARDO., DUMASR.: Anomalies cardio-respiratoires dans la scl~rose en plaques. Rev. Neurol. (Paris) 144, 4, 284-88, 1988. [2] NORONHAM.J., VAS C.J., AZlZH.: Autonomic dysfunction in muln'ple sclerosis. J. Neurol. Neurosurg, Psychiatry, 31:19-22, 1968. [3] OCHIAIY., YOKOJAMAM., KOSOKABEY., ABE S., TANIGUCHIM., TADA K." Intensive care of multiple sclerosis with bulbar palsy. J. Intensive Care
438
Med. (Tokyo) _5:579-86, 1981. [4] STEFOSKID., Davis F.A.: Central disturbances of respiration in multiple sclerosis. In: W.J. Weiner (Ed.), Respiratory dysfunction in neurologic disease. Futura Mount Kisco NY pag. 187-196, 1980. [5] THEODOREJ., ROBINE.D.: Speculations on neurogenic pulmonary edema. Ann. Rev. Respir. Dis., 113:405-11, 1976. [61 TORN YAMAMOTO, TERUKUNI IMAI, MASAHIRO YAMASAKI: Acute ventilator3, f a i l u r e in multiple
sclerosis. J. Neurol. Sci., 89:313-24, 1989.
