J Neurosurg 76:696-700. 1992
Malignant lymphoma of the central nervous system presenting with central neurogenic hyperventilation Case report YASUSHI SHIBATA, M.D., KOTOO NIEGURO+ M.D.F.R.C.S.(C), KIYOSHI NARUSHIMA, M.D., FUMIltO SHIBUYA, M.D., Mm~o DoI, M.D., AND YOICHI KmUCHI, M.D. Departments of Neurosurgery, Pathology, and Radiology, Tsukuba Medical Center Hospital, Tsukuba, Ibaraki, Japan v, The case is described of a 72-year-old woman who presented with a progressive fight hemiparesis and central neurogenic hyperventilation. Pathological and radiological studies revealed diffuse infiltration of a malignant lymphoma into the entire central nervous system and the upper spinal cord. The authors review 12 cases of tumor-induced central neurogenichyperventilationand discuss the palhophysiologyof this condition. KEY W o a D s 9 central nervous system magnetic resonance imaging
ENTRAL neurogenic hyperventilation is commonly encountered in comatose patients who have gross intracranial lesions. However, it is a rare finding in an awake patient. We recently treated an awake patient with tumor-induced central neurogenic hyperventilation. Autopsy of the central nervous system (CNS) revealed diffuse infiltration of a malignant lymphoma into the entire CNS and the upper spinal cord. We review the literature of tumor-induced central neurogenic hyperventilation and discuss the pathophysiology of hyperventilation.
C
Case
Report
This 72-year-old woman was initially seen by a family physician on January 17, 1990, for evaluation of right lower-extremity weakness lasting for 1 month. Computerized tomography (CT) showed no abnormal findings; however, her right-sided paresis progressed to involve the right upper extremity, so she was referred to our hospital on January 22, 1990. Examination. The patient was alert on admission, and physical examination was normal except for the neurological findings. She was found to have a right hemiparesis and bypesthesia, general hyperreflexia, and urinary incontinence. A CT scan disclosed multiple bilateral low-density areas in the white matter. Findings on cerebral angiography were almost normal. The ini696
.
hyperventilation
.
lymphoma
9
tial diagnosis was multiple cerebral infarction. Intravenous infusion of low-molecular-weight dextran and urokinase had no effect. Course. In early February, 1990, the patient started to experience fast, deep respirations, which persisted during sleep. Arterial blood gas measurements, obtained with room-air ventilation, revealed a pH of 7.613, pCO2 17.4 mm Hg, and pO2 100 mm Hg, suggesting the presence of hypocapnea, slight hyperoxycemia, and marked respiratory alkalosis. We investigated the cause of the hyperventilation. Chest roentgenography and echocardiography indicated no pathology such as pulmonary fibrosis, congestive heart failure, or pulmonary embolism. Lumbar cerebrospinal fluid (CSF) analysis revealed mild pleocytosis with lymphocyte dominance and a slightly elevated protein level. Cytological study demonstrated no other abnormalities in the CSF, and other laboratory data and cerebral angiograpby findings were negative for autoimmune disease or cerebral vasculitis. Follow-up CT on March 6 disclosed an increase of the left parietal low-density area. Magnetic resonance (MR) images of the brain stem showed no abnormality except for a possible lesion in the pons suggested by a long signal on the T2-weighted image. Enhanced CT on April 6 and MR imaging on April 11 disclosed well-enhanced lesions in the paraventricular white matter bilaterally with infiltration to the corpus callosum and a left-sided J. Neurosurg. / Volume 76/April. 1992
Lymphoma of the CNS with central neurogenic hyperventilation
FXG. 1. Computerized tomography scans with contrast enhancement obtained on April 6, 1990, showing well-enhanced multiple lesions in the paraventricular white matter bilaterally with infiltration to the corpus callosum. The left-sided enhanced lesion is seen extending to the cerebral peduncle. Note that there is little edema or mass effect. enhanced lesion extending to the pons along the corticospinal tract (Figs. 1, 2, and 3). A biopsy of the lesion was scheduled but the patient died of severe p n e u m o n i a on April 15, 1990.
Postmortem Examination. An autopsy of the brain only was permitted. Macroscopically, there was an obvious area of discoloration in the white matter and the brain stem, corresponding to the lesion delineated
PIG. 2. Magnetic resonance images ot~talned on A o r u 1 1, IYYU. 1 ~-we~gnteo~mages (upper) ~l K 3uu msec, TE 14 msec) and proton-weighted images (lower) (TR 2000 msec, TE 30 msec), axial view, demonstrating T~and T2-elongated lesions in the paraventricular white matter bilaterally and in lhe left pons. There is little edema or mass effect. J. Neurosurg. / Volume 76 /April. 1992
697
Y. Shibata, et al.
Flea..~.
lu
It~StkIlall~'e l l l l a g t ~ s o D t a l l l e U
O l l /~_pill l Z, l ' J ' / k ) . ~,.I'~I.tlOIIIIIUlII-L/I V/~-~Illl~l.lltJtXl I i - w e l g i l l . e u
images (TR 300 msec. TE 14 msec), axial (upper) and coronal (lower) views, showing well-enhanced lesions in the paraventficular white matter bilaterallywith involvement of the corpus callosum. The left-sided enhanced lesion is seen extending into the pons with little edema or mass effect.
by MR imaging. Magnetic resonance study of the formaldehyde-fixed brain specimen showed almost the same appearance as the in vivo MR study obtained on April I 1. Histologically, tumor cells had infiltrated diffusely around the perivascular space in the white matter of the entire CNS (Fig. 4). Immunohistological staining revealed B cell lymphoma in the perivascular space and an abundance of reactive T cell lymphocytes. Tumor cells had infiltrated along the vessel and tract, especially the left corticospinal tract down to the upper cervical spinal cord. Infiltration by tumor cells was also found
FIG. 4. Photomicrograph of a brain section showing diffuse infiltration of malignant lymphoma cells into the perivascular space. H & E, x 400. 698
in the entire CNS beyond the area of the gadoliniumenhanced lesion on the MR image. In the pons, the tegmentum was widely invaded by tumor cells without mass effect, in addition to the tumor nodule in the basis pontis.
Discussion Literature Review Central neurogenic hypcrventilation in the strict sense is a rare neurological finding. Plum and Swanson '~ reported nine cases of central neurogenic hyperventilation with brain-stem infarction. Complete autopsy of six cases showed necrosis of the central portion of the pons in five and compression of the pons in one. The common lesion of all six cases was the infarction of the medial pontine nuclei, medial pontine reticular formation, and the corticospinal tract in the pons. The lateral pontine reticular formation and laterally located fiber tract were spared. The authors proposed that central neurogenic hyperventilation results from uninhibited stimulation of the respiratory center (both inspiratory and expiratory) in the medulla by the lateral pontine reticular formation and by the laterally located descending neural pathway. However, these patients had suffered moderate to extensive bronchopneumonia or pulmonary congestion. The PaO2 levels in these patients were below normal and disproportionate to the extent of hyperventilationY In a later hypothesis, Plum ~ postulated that local stimulation of a chemosensitive area by hydrogen ions produced by a tumor could result in central hyperventilation. However, posJ. Neurosurg. / Volume 76/April, 1992
Lymphoma of the CNS with central neurogenic hyperventilation TABLE 1 Reported cases ~f tumor-induced central neurogenic hjl~erventilation* Case Authors & Year No. 1 2 3 4 5 6 7 8 9 10 I1 12 13
Suzuki. et al., 1964 Lange & Laszlo, 1965 Goulon, et al., 1969 Tinaztepe, et at., 1981 Rodriguez, et al., 1982 Plum, 1982 Sunderrajan & Passamonte, 1984 Bateman, et al., 1985 Nakasu, et al., 1988 Pauzner, et al., 1989 Salvesen, 1989 Shibata, et aL, 1992
Age (yrs), Sex
Diagnosis
Method of Diagnosis
5, M 51. M 22. M 7. M 53, F 8. M 39, M 41, M 62. F 7, F 61, F 48, M 72, F
astrocytoma lymphoma astrocytoma lymphoma astrocytoma unknown unknown lymphoma lymphoma astrocytoma lymphoma unknown lymphoma
autopsy autopsy autopsy autopsy autopsy pneumoencephalography CT CT. biopsy autopsy extirpation CSF cytology MRI autopsy
Areaof Involvement Ports
Medulla
+ + + + + + + unknown + unknown + +
unknown + + + unknown unknown unknown + unknown unknown +
* CT = computerizedtomography;CSF = cerebrospinalfluid; MRI = magneticresonanceimaging.+ indicatesarea was involved;- indicates area not involved.
itron emission tomography studies have revealed that the pH of the tumor in vivo is always more alkaline
than the gray or white matter.1'1 Bateman, et -
al., l
argued
against local acidification of the CSF in the region of the brain stem as the mechanism of hyperventilation on the basis that central neurogenic hylxrventilation is very rare despite the relative frequency of meningeal carcinomatosis. Ngai and Wang 6 reported hyperventilation by electrolysis of the dorsolateral pons of cats. Other authors have failed subsequently to produce hyperventilation in similar experiments, l~ Central vs. Pulmonary Hyperventilation Hyperventilation in comatose patients with intracranial disorders is sometimes regarded as central neurogenic hylxrventilation but is often pulmonary in origin. Acute intracranial lesions such as hemorrhage or infarction are frequently accompanied by pulmonary complications. The increase of catecholamine and hypertension contributes to pulmonary congestion, and this disturbance of consciousness may result in pneumonia. In the majority of cases, hyperventilation with intracranial disorders appears to be due to pulmonary complications. Pathogenesis of Central Neurogenic Hyperventilation We reviewed 13 cases of tumor-induced central neurogenic hyperventilation including our own case t~.a.~.7.s. ,t.t~-16 (Table l). Involvement of the pons was present in 10 cases and absent in one. Although the case reported by Bateman, et al., 1revealed no lesion below the midbrain at autopsy, a pontine lesion seems to be the responsible lesion of central neurogenic hy~rventilation in most cases. Tumor infiltration in the medulla was recognized in four cases with microscopic examination..2 11 916 These findings did not support the hypothJ. Neurosurg. / Volume 76/April, 1992
esis that central neurogenic hyperventilation is caused by the uninhibited stimulation of the respiratory center in the intact medulla. Among 13 cases of tumor-induced hyperventilation, six were lymphoma, four were astrocytoma, and three were of unknown pathology. Malignant lymphoma is a rare tumor, representing fewer than 1% of primary brain tumors) The relative high frequency of lymphoma among cases of tumor-induced hyperventilation appears significant. For this reason, the possibility of a CNS malignant lymphoma should be kept in mind in the case of central neurogenic hyperventilation. What is the common denominator responsible for central neurogenic hyperventilation among these 13 cases? One of the common features may be diffuse infiltration of tumor cells in the pons. Lymphomas are known to be infiltrative, and the four cases of astrocytoma involved the entire ports. It can be postulated that, to produce central neurogenic hyperventilation, the pons should be infiltrated diffusely but should preserve its structure without major destruction. In our case, a gadolinium-enhanced lesion along the pyramidal tract on the MR image was not considered sufficient to cause central neurogenic hyperventilation. However, further postmortem microscopic examination revealed tumor cells throughout the entire ports. Neuroradiographic Studies Gadolinium-enhanced MR imaging is more accurate in determining the area of the lesion than contrastenhanced CT. However, MR imaging was limited as evidenced by the fact that the pathological study revealed more extensive tumor-cell infiltration. The clinical findings, including progressive hemiparesis, were well correlated with gadolinium-enhanced MR imaging which showed a probable area of blood-brain barrier disruption. Gadolinium-enhanced MR imaging is the most useful radiological study in delineating an area 699
Y. Shibata, et a[. of brain edema, but tumor cells without edema may not be recognized even on gadolinium-enhanced MR images. References
1. Bateman DE, Gibson GL, Hudgson P, et al: Central neurogenic hyperventilation in a conscious patient with a primary cerebral lymphoma. Ann Neurol 17:402--405. 1985 2. Goulon M, Escourolle R, Augustin P, et al: Hyperventilation primitive par gliome bulbo-protubrrantiel. Rev Neurol 121:636-639, 1969 3. HochbergFH, MillerDC: Primary central nervous system lymphoma. J Neurnsurg 68:835-853, 1988 4. Lange LS, Laszlo G: Cerebral tumour presenting with hyperventilation. J Neurol Neurosurg Psychiatry 28: 317-319, 1965 5. Nakasu Y, Nakasu S, Matsuda M, et al: [Central neurogenie hyperventilation with pontine tumor. Case report and a review of the literature.] Nippon Geka Hokan 57: 165-171, 1988 {Jpn) 6. Ngai SH, Wang SC: Organization of central respiratory mechanisms in the brain stem of the cat: localization by stimulation and destruction. Am J Physiol 190: 343-349, 1957 7. Pauzner R, Mouallem M, Sadeh M, etal: High incidence of primary cerebral lymphoma in tumor-induced central neurogenic hypervenlflation. Arch Neurol 46:510--512, 1989 8. Plum F: Mechanisms of "central" hyperventilation. Ann Neurol 11:636-637, 1982 (Letter)
7'00
9. Plum F. Posner JB: The Diagnosis of Stupor and Coma, ed 3. Philadelphia: FA Davis, 1980 10. Plum F, Swanson AG: Central neurogenic hyperventilalion in man. Arch Neurol Psychiatry 81:535-549, 1959 11. Rodriguez M, Baele PL, Marsh HM, etal: Central neurogenic hyperventilation in an awake patient with brainstem astrocytoma. Ann Neurol 11:625-628, 1982 12. Rottenberg DA, Ginos JZ, Keaffott KJ, et al: In vivo measurement of brian tumor pH using dimethyloxazolidinedione and positron emission tomography. Ann Neurol 16:132-133, 1984 (Abstract) 13. Salvesen R: Pontine tumour with central neurogenic hyperventilation. J Neurol Neurosurg Psychiatry 52: 1441-1442, 1989 (Letter) 14. Sunderrajan EV, Passamonte PM: Lymphomatoid granulomatosis presenting as central neurogenic hyperventilation. Chest 86:634-636, 1984 15. Suzuki M, Kawakatsu T, Kameshita S, et ah A case of pontine tumor associated with repeated episodes of hyperventilation and ketosis. Paediatr Univ Tokyo 10: 58-62, 1964 16. Tinaztepe B, Tinaztepe K, Yalaz K, et ah Microgliomatosis presenting as sustained hyperventilation. Turk J Pediatr 23:269-275, 1981
Manuscript received May 21, 1991. Accepted in final form September 9, 1991. Address reprint requests to: Yasushi Shibata, M.D., Department of Neurosurgery, Tsukuba Medical Center Hospital, Tsukuba, Ibaraki 305, Japan.
J. Neurosurg. / Volume 76/April, 1992
Malignant lymphoma of the central nervous system presenting with central neurogenic hyperventilation Case report YASUSHI SHIBATA, M.D., KOTOO NIEGURO+ M.D.F.R.C.S.(C), KIYOSHI NARUSHIMA, M.D., FUMIltO SHIBUYA, M.D., Mm~o DoI, M.D., AND YOICHI KmUCHI, M.D. Departments of Neurosurgery, Pathology, and Radiology, Tsukuba Medical Center Hospital, Tsukuba, Ibaraki, Japan v, The case is described of a 72-year-old woman who presented with a progressive fight hemiparesis and central neurogenic hyperventilation. Pathological and radiological studies revealed diffuse infiltration of a malignant lymphoma into the entire central nervous system and the upper spinal cord. The authors review 12 cases of tumor-induced central neurogenichyperventilationand discuss the palhophysiologyof this condition. KEY W o a D s 9 central nervous system magnetic resonance imaging
ENTRAL neurogenic hyperventilation is commonly encountered in comatose patients who have gross intracranial lesions. However, it is a rare finding in an awake patient. We recently treated an awake patient with tumor-induced central neurogenic hyperventilation. Autopsy of the central nervous system (CNS) revealed diffuse infiltration of a malignant lymphoma into the entire CNS and the upper spinal cord. We review the literature of tumor-induced central neurogenic hyperventilation and discuss the pathophysiology of hyperventilation.
C
Case
Report
This 72-year-old woman was initially seen by a family physician on January 17, 1990, for evaluation of right lower-extremity weakness lasting for 1 month. Computerized tomography (CT) showed no abnormal findings; however, her right-sided paresis progressed to involve the right upper extremity, so she was referred to our hospital on January 22, 1990. Examination. The patient was alert on admission, and physical examination was normal except for the neurological findings. She was found to have a right hemiparesis and bypesthesia, general hyperreflexia, and urinary incontinence. A CT scan disclosed multiple bilateral low-density areas in the white matter. Findings on cerebral angiography were almost normal. The ini696
.
hyperventilation
.
lymphoma
9
tial diagnosis was multiple cerebral infarction. Intravenous infusion of low-molecular-weight dextran and urokinase had no effect. Course. In early February, 1990, the patient started to experience fast, deep respirations, which persisted during sleep. Arterial blood gas measurements, obtained with room-air ventilation, revealed a pH of 7.613, pCO2 17.4 mm Hg, and pO2 100 mm Hg, suggesting the presence of hypocapnea, slight hyperoxycemia, and marked respiratory alkalosis. We investigated the cause of the hyperventilation. Chest roentgenography and echocardiography indicated no pathology such as pulmonary fibrosis, congestive heart failure, or pulmonary embolism. Lumbar cerebrospinal fluid (CSF) analysis revealed mild pleocytosis with lymphocyte dominance and a slightly elevated protein level. Cytological study demonstrated no other abnormalities in the CSF, and other laboratory data and cerebral angiograpby findings were negative for autoimmune disease or cerebral vasculitis. Follow-up CT on March 6 disclosed an increase of the left parietal low-density area. Magnetic resonance (MR) images of the brain stem showed no abnormality except for a possible lesion in the pons suggested by a long signal on the T2-weighted image. Enhanced CT on April 6 and MR imaging on April 11 disclosed well-enhanced lesions in the paraventricular white matter bilaterally with infiltration to the corpus callosum and a left-sided J. Neurosurg. / Volume 76/April. 1992
Lymphoma of the CNS with central neurogenic hyperventilation
FXG. 1. Computerized tomography scans with contrast enhancement obtained on April 6, 1990, showing well-enhanced multiple lesions in the paraventricular white matter bilaterally with infiltration to the corpus callosum. The left-sided enhanced lesion is seen extending to the cerebral peduncle. Note that there is little edema or mass effect. enhanced lesion extending to the pons along the corticospinal tract (Figs. 1, 2, and 3). A biopsy of the lesion was scheduled but the patient died of severe p n e u m o n i a on April 15, 1990.
Postmortem Examination. An autopsy of the brain only was permitted. Macroscopically, there was an obvious area of discoloration in the white matter and the brain stem, corresponding to the lesion delineated
PIG. 2. Magnetic resonance images ot~talned on A o r u 1 1, IYYU. 1 ~-we~gnteo~mages (upper) ~l K 3uu msec, TE 14 msec) and proton-weighted images (lower) (TR 2000 msec, TE 30 msec), axial view, demonstrating T~and T2-elongated lesions in the paraventricular white matter bilaterally and in lhe left pons. There is little edema or mass effect. J. Neurosurg. / Volume 76 /April. 1992
697
Y. Shibata, et al.
Flea..~.
lu
It~StkIlall~'e l l l l a g t ~ s o D t a l l l e U
O l l /~_pill l Z, l ' J ' / k ) . ~,.I'~I.tlOIIIIIUlII-L/I V/~-~Illl~l.lltJtXl I i - w e l g i l l . e u
images (TR 300 msec. TE 14 msec), axial (upper) and coronal (lower) views, showing well-enhanced lesions in the paraventficular white matter bilaterallywith involvement of the corpus callosum. The left-sided enhanced lesion is seen extending into the pons with little edema or mass effect.
by MR imaging. Magnetic resonance study of the formaldehyde-fixed brain specimen showed almost the same appearance as the in vivo MR study obtained on April I 1. Histologically, tumor cells had infiltrated diffusely around the perivascular space in the white matter of the entire CNS (Fig. 4). Immunohistological staining revealed B cell lymphoma in the perivascular space and an abundance of reactive T cell lymphocytes. Tumor cells had infiltrated along the vessel and tract, especially the left corticospinal tract down to the upper cervical spinal cord. Infiltration by tumor cells was also found
FIG. 4. Photomicrograph of a brain section showing diffuse infiltration of malignant lymphoma cells into the perivascular space. H & E, x 400. 698
in the entire CNS beyond the area of the gadoliniumenhanced lesion on the MR image. In the pons, the tegmentum was widely invaded by tumor cells without mass effect, in addition to the tumor nodule in the basis pontis.
Discussion Literature Review Central neurogenic hypcrventilation in the strict sense is a rare neurological finding. Plum and Swanson '~ reported nine cases of central neurogenic hyperventilation with brain-stem infarction. Complete autopsy of six cases showed necrosis of the central portion of the pons in five and compression of the pons in one. The common lesion of all six cases was the infarction of the medial pontine nuclei, medial pontine reticular formation, and the corticospinal tract in the pons. The lateral pontine reticular formation and laterally located fiber tract were spared. The authors proposed that central neurogenic hyperventilation results from uninhibited stimulation of the respiratory center (both inspiratory and expiratory) in the medulla by the lateral pontine reticular formation and by the laterally located descending neural pathway. However, these patients had suffered moderate to extensive bronchopneumonia or pulmonary congestion. The PaO2 levels in these patients were below normal and disproportionate to the extent of hyperventilationY In a later hypothesis, Plum ~ postulated that local stimulation of a chemosensitive area by hydrogen ions produced by a tumor could result in central hyperventilation. However, posJ. Neurosurg. / Volume 76/April, 1992
Lymphoma of the CNS with central neurogenic hyperventilation TABLE 1 Reported cases ~f tumor-induced central neurogenic hjl~erventilation* Case Authors & Year No. 1 2 3 4 5 6 7 8 9 10 I1 12 13
Suzuki. et al., 1964 Lange & Laszlo, 1965 Goulon, et al., 1969 Tinaztepe, et at., 1981 Rodriguez, et al., 1982 Plum, 1982 Sunderrajan & Passamonte, 1984 Bateman, et al., 1985 Nakasu, et al., 1988 Pauzner, et al., 1989 Salvesen, 1989 Shibata, et aL, 1992
Age (yrs), Sex
Diagnosis
Method of Diagnosis
5, M 51. M 22. M 7. M 53, F 8. M 39, M 41, M 62. F 7, F 61, F 48, M 72, F
astrocytoma lymphoma astrocytoma lymphoma astrocytoma unknown unknown lymphoma lymphoma astrocytoma lymphoma unknown lymphoma
autopsy autopsy autopsy autopsy autopsy pneumoencephalography CT CT. biopsy autopsy extirpation CSF cytology MRI autopsy
Areaof Involvement Ports
Medulla
+ + + + + + + unknown + unknown + +
unknown + + + unknown unknown unknown + unknown unknown +
* CT = computerizedtomography;CSF = cerebrospinalfluid; MRI = magneticresonanceimaging.+ indicatesarea was involved;- indicates area not involved.
itron emission tomography studies have revealed that the pH of the tumor in vivo is always more alkaline
than the gray or white matter.1'1 Bateman, et -
al., l
argued
against local acidification of the CSF in the region of the brain stem as the mechanism of hyperventilation on the basis that central neurogenic hylxrventilation is very rare despite the relative frequency of meningeal carcinomatosis. Ngai and Wang 6 reported hyperventilation by electrolysis of the dorsolateral pons of cats. Other authors have failed subsequently to produce hyperventilation in similar experiments, l~ Central vs. Pulmonary Hyperventilation Hyperventilation in comatose patients with intracranial disorders is sometimes regarded as central neurogenic hylxrventilation but is often pulmonary in origin. Acute intracranial lesions such as hemorrhage or infarction are frequently accompanied by pulmonary complications. The increase of catecholamine and hypertension contributes to pulmonary congestion, and this disturbance of consciousness may result in pneumonia. In the majority of cases, hyperventilation with intracranial disorders appears to be due to pulmonary complications. Pathogenesis of Central Neurogenic Hyperventilation We reviewed 13 cases of tumor-induced central neurogenic hyperventilation including our own case t~.a.~.7.s. ,t.t~-16 (Table l). Involvement of the pons was present in 10 cases and absent in one. Although the case reported by Bateman, et al., 1revealed no lesion below the midbrain at autopsy, a pontine lesion seems to be the responsible lesion of central neurogenic hy~rventilation in most cases. Tumor infiltration in the medulla was recognized in four cases with microscopic examination..2 11 916 These findings did not support the hypothJ. Neurosurg. / Volume 76/April, 1992
esis that central neurogenic hyperventilation is caused by the uninhibited stimulation of the respiratory center in the intact medulla. Among 13 cases of tumor-induced hyperventilation, six were lymphoma, four were astrocytoma, and three were of unknown pathology. Malignant lymphoma is a rare tumor, representing fewer than 1% of primary brain tumors) The relative high frequency of lymphoma among cases of tumor-induced hyperventilation appears significant. For this reason, the possibility of a CNS malignant lymphoma should be kept in mind in the case of central neurogenic hyperventilation. What is the common denominator responsible for central neurogenic hyperventilation among these 13 cases? One of the common features may be diffuse infiltration of tumor cells in the pons. Lymphomas are known to be infiltrative, and the four cases of astrocytoma involved the entire ports. It can be postulated that, to produce central neurogenic hyperventilation, the pons should be infiltrated diffusely but should preserve its structure without major destruction. In our case, a gadolinium-enhanced lesion along the pyramidal tract on the MR image was not considered sufficient to cause central neurogenic hyperventilation. However, further postmortem microscopic examination revealed tumor cells throughout the entire ports. Neuroradiographic Studies Gadolinium-enhanced MR imaging is more accurate in determining the area of the lesion than contrastenhanced CT. However, MR imaging was limited as evidenced by the fact that the pathological study revealed more extensive tumor-cell infiltration. The clinical findings, including progressive hemiparesis, were well correlated with gadolinium-enhanced MR imaging which showed a probable area of blood-brain barrier disruption. Gadolinium-enhanced MR imaging is the most useful radiological study in delineating an area 699
Y. Shibata, et a[. of brain edema, but tumor cells without edema may not be recognized even on gadolinium-enhanced MR images. References
1. Bateman DE, Gibson GL, Hudgson P, et al: Central neurogenic hyperventilation in a conscious patient with a primary cerebral lymphoma. Ann Neurol 17:402--405. 1985 2. Goulon M, Escourolle R, Augustin P, et al: Hyperventilation primitive par gliome bulbo-protubrrantiel. Rev Neurol 121:636-639, 1969 3. HochbergFH, MillerDC: Primary central nervous system lymphoma. J Neurnsurg 68:835-853, 1988 4. Lange LS, Laszlo G: Cerebral tumour presenting with hyperventilation. J Neurol Neurosurg Psychiatry 28: 317-319, 1965 5. Nakasu Y, Nakasu S, Matsuda M, et al: [Central neurogenie hyperventilation with pontine tumor. Case report and a review of the literature.] Nippon Geka Hokan 57: 165-171, 1988 {Jpn) 6. Ngai SH, Wang SC: Organization of central respiratory mechanisms in the brain stem of the cat: localization by stimulation and destruction. Am J Physiol 190: 343-349, 1957 7. Pauzner R, Mouallem M, Sadeh M, etal: High incidence of primary cerebral lymphoma in tumor-induced central neurogenic hypervenlflation. Arch Neurol 46:510--512, 1989 8. Plum F: Mechanisms of "central" hyperventilation. Ann Neurol 11:636-637, 1982 (Letter)
7'00
9. Plum F. Posner JB: The Diagnosis of Stupor and Coma, ed 3. Philadelphia: FA Davis, 1980 10. Plum F, Swanson AG: Central neurogenic hyperventilalion in man. Arch Neurol Psychiatry 81:535-549, 1959 11. Rodriguez M, Baele PL, Marsh HM, etal: Central neurogenic hyperventilation in an awake patient with brainstem astrocytoma. Ann Neurol 11:625-628, 1982 12. Rottenberg DA, Ginos JZ, Keaffott KJ, et al: In vivo measurement of brian tumor pH using dimethyloxazolidinedione and positron emission tomography. Ann Neurol 16:132-133, 1984 (Abstract) 13. Salvesen R: Pontine tumour with central neurogenic hyperventilation. J Neurol Neurosurg Psychiatry 52: 1441-1442, 1989 (Letter) 14. Sunderrajan EV, Passamonte PM: Lymphomatoid granulomatosis presenting as central neurogenic hyperventilation. Chest 86:634-636, 1984 15. Suzuki M, Kawakatsu T, Kameshita S, et ah A case of pontine tumor associated with repeated episodes of hyperventilation and ketosis. Paediatr Univ Tokyo 10: 58-62, 1964 16. Tinaztepe B, Tinaztepe K, Yalaz K, et ah Microgliomatosis presenting as sustained hyperventilation. Turk J Pediatr 23:269-275, 1981
Manuscript received May 21, 1991. Accepted in final form September 9, 1991. Address reprint requests to: Yasushi Shibata, M.D., Department of Neurosurgery, Tsukuba Medical Center Hospital, Tsukuba, Ibaraki 305, Japan.
J. Neurosurg. / Volume 76/April, 1992
