- Email: [email protected]
Apnea as the sole manifestation of cord compression in achondroplasia
CLINICAL A N D LABORATORY OBSERVATIONS
Articles in this section should require no more than three Journal pages, the text 1000 words or less. A combined total of two illustrations or tables and up to 10 references will be accepted. An abstract is not necessary.
Apnea as the sole manifestation of cord compression in achondroplasia Amy S. Fremion, M.D., Bhuwan P. Garg, M.B.B.S., and John Kalsbeck, M.D. I n d i a n a p o l i s , Ind.
ACtlONDROPLASIA is an autosomal d o m i n a n t disorder characterized by inhibition of endochondral bone formation. The base of the skull is affected, but the membranous bones of the skull grow normally. This results in a large calvarium on a small base and spinal stenosis. Hydrocephalus is often present) W e describe achondroplasia in two patients with recurrent hypoventilatory syndrome as the sole manifestation of medulloccrvical compression. CASE REPORTS Patient I. This achondroplastic infant was admitted to Riley Children's Hospital at age 9 months for further evaluation of apneic spells. The patient was the product of a term pregnancy in a 29year-old white woman. Delivery was by cesarean section because of breech presentation. The patient had three apneic spells shortly after delivery that spontaneously resolved. No further apneie spells occurred until 15 days of age, when the patient was found cyanotic after awakening from a nap. tte was hospitalized and became apneic four times during the hospitalization. An electroencephalogram showed diffusely slow brain waves, and results of a computed tomographic scan of the head were normal. A sleep EEG yielded unremarkable findings, as did a pneumogram. The patient was discharged to home with an apnea monitor. At different times he was given phenobarbital, ethosuximide, phenytoin, and valproate without a decrease in the frequency of apneie
From the Departnwnts of Neurology and Neurosurgery, Indiana University School of Medicine. Presented in part at the American Academy of Neurology meeting. San Diego. April 28, 1983. Reprint requests: Amy S. Fremion, M.D., Department of Neurology. Rile)' NI02, 702 Barnhill Dr., Indianapolis, IN 46223.
398
The Journal of P E D I A T R I C S Vol. 104, No. 3, March 1984
spells, which continued to occur in clusters of eight to twelve every 3 to 4 weeks. Developmental history was normal except for difficulty holding up his large head. The patient's father, who also had aehondroplasia, had had apneic spells between 7 and 9 months of age, which stopped spontaneously. Examination on admission showed an occipitofrontal circumference of 53 cm (>98th percentile for a 9-month-old boy with t achondroplasia). Results of chest and cardiac examinations were normal. The patient could hold his head up when sitting. There were no abnormal neurologic findings.
See related article, p. 342.
SER
Somatosensory evoked responses
I
During the hospitalization a repeat CT head scan was obtained, which yielded normal findings. An EEG showed diffuse slowing of brain waves. Long-latency somatoscnsory evoked responses after stimulation of the right and left median nerves were 19.6 msec and 18.6 mscc, respectively. Posterior tibial nerve stimulation at 2/see produced SERs with a latency of 36.5 msee on the right and 35 msec on the left. These values are significantly prolonged for the patient's age and stature, the site of impairment being rostral to the cervical cord. CT of the foramen magnum and upper cervical spine showed narrowing at the foramen magnum and CI. Anteroposterior diameter of the patient's foramen was 21 mm (normal 30 mm).(Fig. I). AP diameter at CI measured 13 mm, which is also below the lower limits of normal. The AP diameter at C2 was normal. The patient underwent posterior fossa decompression and C I laminectomy. ! le had two brief episodes of pcrioral cyanosis in the immediate postoperative period. He was discharged to home without anticonvulsant therapy. On follow-up 6 months after
Volume 104 Number 3
Fig. I. A, CT scan of foramen magnum in patient I, showing narrowing of AP and lateral diameters. B, CT scan of foramen magnum in normal 9-month-old child.
discharge, the parents reported no incidents of cyanosis or apnea. Patient 2. This 5-year-old boy with achondroplasia was admitted to Riley Children's Ilospital with acute respiratory distress. Ten days prior to admission he began having episodes of cyanosis, during which he was difficult to arouse. He would awaken on stimulation, but fall back to sleep immediately. Each spell would last for an entire day, followed by a normal day. One day prior to admission to Riley Children's Ilospital he was admitted to a local hospital with a presumptive diagnosis of congestive heart failure. When he did not respond to treatment, he was transferred. The patient was the 1644 gm product of 32 weeks" gestation in a mother with achondroplasia. Delivery was by cesarean section because of placenta previa. The patient remained in the hospital for 3 weeks after birth. The only complication was neonatal
Clinical attd laboratory observations
399
Fig. 2. A, CT scan of foramen magnum in patient 2, showing narrowing of AP and lateral diameters. B, CT scan of foramen magnum in normal 5-year-old child.
jaundice. Ile did not require ventilatory support. His development was normal except for minimal delay in walking, and at the time of admission he could recite the alphabet, count to 10, write his name, and dress himself, tie was receiving no medications. The patient's brother, mother, and maternal grandfather had achondroplasia. The brother (patient 3) was admitted to Riley Children's Hospital at the age of 3 years because of an episode of respiratory arrest during pneumonia. Physical examination on admission showed moderate respiratory distress. OFC was 60 cm (98th percentile for a boy with achondroplasia). Chest, cardiac, and neurologic examinations yielded normal results. Arterial blood gas values on admission, during 40% Fio2, were
400
Clinical and laboratory observations
Poz 125 torr, Pcoz I 10 torr, and pH 7.16. Tracheal inlubation and mechanical ventilation resulted in normal arterial blood gas values. ECG and echocardiogram showed normal findings. ACT scan of the head showed prominent ventriclesand a small foramen magnum (Fig. 2). A cervical myelogram showed narrowing at the superior aspect of C2, extending through CI. An EEG showed moderately diffuseslowing for age and a possiblemid-vertex spike focus. The patient underwent a decompressivesuboccipital eraniectomy and C I-3 cervical laminectomy, tlis postoperative course was uneventful, and he has had no more episodes of cyanosis. Patient 3. This boy, the brother of patient 2, had been hospitalized numerous times between 3 months and 3 years of age because of pneumonia, tlis development had been normal except for slightly delayed walking, lte had undergone foramen magnum decompression and was able to be weaned from the ventilator during the postoperative period. Later, he developed pneumonia, his lungs could not be adequately ventilated, and he died. Autopsy showed softening and cavity formation in the upper spinal cord extending from 8 mm to 2 mm below the medulla. Microscopic examination of the cord at this level showed a densely gliotie area with cystic degeneration. DISCUSSION Compression of a normal-sized medulla and cervical cord in a small foramen magnum and vertebral canal is not infrequent in achondroplasia3 Compression of the medulla may result in hypoventilation because of dysfunction of fibers emerging from the respiratory center. 3 The respiratory apparatus remains responsive to voluntary efforts, so that patients can breathe on command, but not while asleep. Lesions of the cervical cord, on the other hand, cause dysfunction of the lateral pyramidal tracts carrying fibers influencing the innervation of the diaphragm and intercostal muscles.+ The result is paralysis of voluntary respiration with reduction of tidal volume. Cervical myelopathy has been recognized as a complication of achondroplasia since 1901.5 Yamada et al. +reported eight achondroplastic patients between the ages of 3t,5 and 21 months who had feeding problems, poor head control, delayed motor milestones, quadriparesis, and cyanotic attacks after exertion as symptoms of cord compression at the level of the foramen magnum. Six of the eight underwent foramen magnum decompression, with subsequent improvement. Isolated respiratory problems were not seen. Our patients had symptoms of medullary and cervical cord compression giving rise to dysfunction of both involuntary and voluntary respiration. They had greater difficulty while asleep, but were also episodically apneic while awake. Stokes et al.7 recently reported nine children with achondroplasia with respiratory complications resulting from one of four mechanisms: chest deformity, upper airway obstruction and sleep-disordered breathing, coinci-
The Journal of Pediatrics March 1984
dental chronic pulmonary conditions, and neurologic complications. Evidence for any of the first three mechanisms was absent in our patients, whose symptoms resolved after decompressive craniectomy/laminectomy. Yang et al.~ described the pathologic findings in two infants with achondroplasia. Each had a small foramen magnum and evidence of severe damage to the corresponding segment of the upper cervical cord. One newborn baby had respiratory failure; the other died of cardiopulmonary complications at age 6 months. In the first patient, the brainstem was located abnormally posterior to the foramen magnum, causing the upper cervical cord and lower medulla to be angulated anteriorly. Findings on examination of the second patient were unremarkable. Both patients evidenced central gray matter necrosis comparable to that seen following traumatic hyperextension injuries. In our patient 3, microscopic examination of the cord showed a gliotic area with cystic degeneration; the cyst was lined with dysplastic cells. This cervical lesion was the presumed reason this patient died despite foramen magnum decompression. The possibility of cervical cord compression must be considered in young achondroplastic patients with respiratory abnormalities, especially in those who do not have abnormal thoraces, upper airway obstruction, or chronic pulmonary disease. Failure to consider cord compression may result in undue delay before the correct diagnosis is made and corrective surgery performed. Hyperextension of the neck should be avoided whenever possible in achondroplastic patients. It is recognized that all infants with achondroplasia have a small foramen magnum. In one of our patients, prolongation of SER latencies was consistent with cord compression. Data are insufficient to be certain whether SERs alone can be relied on to demonstrate cord compression in achondroplastic children. Cord. compression can be confirmed by CT scans 9f the foramen magnum and upper cervical cord. Surgery should be performed at the first sign of cord compression, as results are poor after extensive damage has occurred. ltydrocephalus is often present in achondroplastic patients of normal intelligence. One theory attributes the hydrocephalus to premature synostoses of the base of the skull, producing obstruction of the ventricular fluid circulation, with internal hydrocephalus. In both of our patients, CT scans after occipital craniectomy showed no decrease in ventricular size. This argues against obstruction at the base of the skull as the cause of their hydrocephalus. REFERENCES I. Langer LO, Baumann PA, Gorlin RJ: Achondroplasia: Clinical radiological features with comment on genetic implications. Clin Pediatr 7:474, 1968.
Volume 104 Number 3
2. Cohen ME, Roscnthal AD, Matson DD: Neurological abnormalities in achondroplastic children. 3 PEDIATR 71:367, 1967. 3. Plum F, Posner J: Diagnosis of stupor and coma. Philadelphia, 1971, FA Davis, p 29. 4. Haymaker W: Bing's local diagnosisin neurologicdisease. St. Louis, 1969, CV Mosby, p 100. 5. Collmann B: Beitag zur Kenntniss der Chondrodystrophia foctalis. Virchows Arch [Pathol Anat] 166:1, 1901.
Clinical and laboratory observations
401
6. Yamada H, Makamura S, Tajima M, Kageyama N: Neurological manifestations of pediatric achondroplasia. J Neurosurg 54:49, 1981. 7. Stokes DC, Phillips JA, Leonard CO, et al: Respiratory complications of achondroplasia. J PEDIA'rR102:534, 1983. 8. Yang SS, Corbett DP, Brough AJ, lteidelberger KP: Upper cervical myelopathy in achondroplasia. Am J Clin Pathol 68:68, 1977.
Superiority o f acridine orange stain versus Gram stain in partially treated bacterial meningitis Martin B. Kleiman, M.D., Janet K. Reynolds, M.S., Nancy H. Watts, M.S., Richard L. Schreiner, M.D., and James W. Smith, M.D. Indianapolis, Ind.
GRAM STAIN EXAMINATION of cerebrospinal fluid often yields rapid, reliable information that is useful in selecting initial antimicrobial therapy for the patient with bacterial infection. Although partial antibiotic treatment may not obscure the cellular changes typical of purulent meningitis, suboptimal treatment can sterilize the CSF, decrease the number of bacteria present, or alter bacterial cell wall structure and function sufficiently to render the Gram stain negative or misleading) Acridine orange [3,6-bis(dimethylamino)acridine] is a lluorochrome that stains the nucleic acids of somatic cells,2 bacteria) and other microorganisms?.: KronvalP first observed that bacteria stained bright orange and the background of cell debris and human cells appeared yellow to pale green when the stain pH was maintained at 3.5 to 5.0, thereby permitting easy identification of bacteria in clinical specimens. The acridine orange stain has been used for detecting malarial parasites in human blood smears, ~.6 gonococci in urethral smears, ~and Trichomonas vaginalis ~ in vaginal secretions. McCarthy and Senne" found the AOS as sensitive as
From the Department of Pediatrics. Sections of Infectious Disease attd Neonatology, and the Department of Pathology, Division of Microbiolog)', Indiana University School of Medicine. Supported by a grant from the Riley Memorial Association. Presented in part at the annual meetings of the Society for Pediatric Research, Washington. D.C.. May 5. 1983. attd the American Academy of Pediatrics, San Francisco, October 24, 1983. Reprint requests: Martin B. Kleiman. M.D.. Section of b:fectious Disease. Department of Pediatrics. James IVhitcomb Riley Hospital for Children. 702 Barnhill, Indianapolis, IN 46223.
subculture for detecting organisms in blood culture bottles that did not demonstrate visible growth after 24 hours. Mirrett et al. 9 found the AOS more sensitive and equally as specific as the Gram and methylene blue stains for early detection of positive blood cultures. Lauer et al) ~ compared the AOS and Gram stains of'direct smears of 487 specimens of body fluids, tissues, and exudates and concluded that the AOS and Gram stain were equally specific, whereas the AOS was slightly more sensitive. Eisenach et
AOS
Acridine orange stain
]
al." examined 14 culture-positive CSF samples and found the AOS positive in 10 and the Gram stain positive in eight. The objectives of our investigation were to compare (1) the sensitivity of the AOS and Gram stain for detecting bacteria in direct smears of CSF obtained before and at intervals during antibiotic treatment, and (2) Gram stain and AOS with culture of CSF obtained during antibiotic treatment. MATERIALS AND METtIODS Cerebrospinal fluid was obtained from 217 children undergoing diagnostic lumbar or ventricular taps between March 1981 and April 1983. All 32 patients with infections caused by Haemophilus influenzae, Neisseria meningitidis, or Streptococcus pneumoniae were between 3 months and I0 years of age. Ten of I1 patients with meningitis caused by group B streptococcus, Streptococcus faecalis, Staphylococcus aureus, Escherichia coli, or
Articles in this section should require no more than three Journal pages, the text 1000 words or less. A combined total of two illustrations or tables and up to 10 references will be accepted. An abstract is not necessary.
Apnea as the sole manifestation of cord compression in achondroplasia Amy S. Fremion, M.D., Bhuwan P. Garg, M.B.B.S., and John Kalsbeck, M.D. I n d i a n a p o l i s , Ind.
ACtlONDROPLASIA is an autosomal d o m i n a n t disorder characterized by inhibition of endochondral bone formation. The base of the skull is affected, but the membranous bones of the skull grow normally. This results in a large calvarium on a small base and spinal stenosis. Hydrocephalus is often present) W e describe achondroplasia in two patients with recurrent hypoventilatory syndrome as the sole manifestation of medulloccrvical compression. CASE REPORTS Patient I. This achondroplastic infant was admitted to Riley Children's Hospital at age 9 months for further evaluation of apneic spells. The patient was the product of a term pregnancy in a 29year-old white woman. Delivery was by cesarean section because of breech presentation. The patient had three apneic spells shortly after delivery that spontaneously resolved. No further apneie spells occurred until 15 days of age, when the patient was found cyanotic after awakening from a nap. tte was hospitalized and became apneic four times during the hospitalization. An electroencephalogram showed diffusely slow brain waves, and results of a computed tomographic scan of the head were normal. A sleep EEG yielded unremarkable findings, as did a pneumogram. The patient was discharged to home with an apnea monitor. At different times he was given phenobarbital, ethosuximide, phenytoin, and valproate without a decrease in the frequency of apneie
From the Departnwnts of Neurology and Neurosurgery, Indiana University School of Medicine. Presented in part at the American Academy of Neurology meeting. San Diego. April 28, 1983. Reprint requests: Amy S. Fremion, M.D., Department of Neurology. Rile)' NI02, 702 Barnhill Dr., Indianapolis, IN 46223.
398
The Journal of P E D I A T R I C S Vol. 104, No. 3, March 1984
spells, which continued to occur in clusters of eight to twelve every 3 to 4 weeks. Developmental history was normal except for difficulty holding up his large head. The patient's father, who also had aehondroplasia, had had apneic spells between 7 and 9 months of age, which stopped spontaneously. Examination on admission showed an occipitofrontal circumference of 53 cm (>98th percentile for a 9-month-old boy with t achondroplasia). Results of chest and cardiac examinations were normal. The patient could hold his head up when sitting. There were no abnormal neurologic findings.
See related article, p. 342.
SER
Somatosensory evoked responses
I
During the hospitalization a repeat CT head scan was obtained, which yielded normal findings. An EEG showed diffuse slowing of brain waves. Long-latency somatoscnsory evoked responses after stimulation of the right and left median nerves were 19.6 msec and 18.6 mscc, respectively. Posterior tibial nerve stimulation at 2/see produced SERs with a latency of 36.5 msee on the right and 35 msec on the left. These values are significantly prolonged for the patient's age and stature, the site of impairment being rostral to the cervical cord. CT of the foramen magnum and upper cervical spine showed narrowing at the foramen magnum and CI. Anteroposterior diameter of the patient's foramen was 21 mm (normal 30 mm).(Fig. I). AP diameter at CI measured 13 mm, which is also below the lower limits of normal. The AP diameter at C2 was normal. The patient underwent posterior fossa decompression and C I laminectomy. ! le had two brief episodes of pcrioral cyanosis in the immediate postoperative period. He was discharged to home without anticonvulsant therapy. On follow-up 6 months after
Volume 104 Number 3
Fig. I. A, CT scan of foramen magnum in patient I, showing narrowing of AP and lateral diameters. B, CT scan of foramen magnum in normal 9-month-old child.
discharge, the parents reported no incidents of cyanosis or apnea. Patient 2. This 5-year-old boy with achondroplasia was admitted to Riley Children's Ilospital with acute respiratory distress. Ten days prior to admission he began having episodes of cyanosis, during which he was difficult to arouse. He would awaken on stimulation, but fall back to sleep immediately. Each spell would last for an entire day, followed by a normal day. One day prior to admission to Riley Children's Ilospital he was admitted to a local hospital with a presumptive diagnosis of congestive heart failure. When he did not respond to treatment, he was transferred. The patient was the 1644 gm product of 32 weeks" gestation in a mother with achondroplasia. Delivery was by cesarean section because of placenta previa. The patient remained in the hospital for 3 weeks after birth. The only complication was neonatal
Clinical attd laboratory observations
399
Fig. 2. A, CT scan of foramen magnum in patient 2, showing narrowing of AP and lateral diameters. B, CT scan of foramen magnum in normal 5-year-old child.
jaundice. Ile did not require ventilatory support. His development was normal except for minimal delay in walking, and at the time of admission he could recite the alphabet, count to 10, write his name, and dress himself, tie was receiving no medications. The patient's brother, mother, and maternal grandfather had achondroplasia. The brother (patient 3) was admitted to Riley Children's Hospital at the age of 3 years because of an episode of respiratory arrest during pneumonia. Physical examination on admission showed moderate respiratory distress. OFC was 60 cm (98th percentile for a boy with achondroplasia). Chest, cardiac, and neurologic examinations yielded normal results. Arterial blood gas values on admission, during 40% Fio2, were
400
Clinical and laboratory observations
Poz 125 torr, Pcoz I 10 torr, and pH 7.16. Tracheal inlubation and mechanical ventilation resulted in normal arterial blood gas values. ECG and echocardiogram showed normal findings. ACT scan of the head showed prominent ventriclesand a small foramen magnum (Fig. 2). A cervical myelogram showed narrowing at the superior aspect of C2, extending through CI. An EEG showed moderately diffuseslowing for age and a possiblemid-vertex spike focus. The patient underwent a decompressivesuboccipital eraniectomy and C I-3 cervical laminectomy, tlis postoperative course was uneventful, and he has had no more episodes of cyanosis. Patient 3. This boy, the brother of patient 2, had been hospitalized numerous times between 3 months and 3 years of age because of pneumonia, tlis development had been normal except for slightly delayed walking, lte had undergone foramen magnum decompression and was able to be weaned from the ventilator during the postoperative period. Later, he developed pneumonia, his lungs could not be adequately ventilated, and he died. Autopsy showed softening and cavity formation in the upper spinal cord extending from 8 mm to 2 mm below the medulla. Microscopic examination of the cord at this level showed a densely gliotie area with cystic degeneration. DISCUSSION Compression of a normal-sized medulla and cervical cord in a small foramen magnum and vertebral canal is not infrequent in achondroplasia3 Compression of the medulla may result in hypoventilation because of dysfunction of fibers emerging from the respiratory center. 3 The respiratory apparatus remains responsive to voluntary efforts, so that patients can breathe on command, but not while asleep. Lesions of the cervical cord, on the other hand, cause dysfunction of the lateral pyramidal tracts carrying fibers influencing the innervation of the diaphragm and intercostal muscles.+ The result is paralysis of voluntary respiration with reduction of tidal volume. Cervical myelopathy has been recognized as a complication of achondroplasia since 1901.5 Yamada et al. +reported eight achondroplastic patients between the ages of 3t,5 and 21 months who had feeding problems, poor head control, delayed motor milestones, quadriparesis, and cyanotic attacks after exertion as symptoms of cord compression at the level of the foramen magnum. Six of the eight underwent foramen magnum decompression, with subsequent improvement. Isolated respiratory problems were not seen. Our patients had symptoms of medullary and cervical cord compression giving rise to dysfunction of both involuntary and voluntary respiration. They had greater difficulty while asleep, but were also episodically apneic while awake. Stokes et al.7 recently reported nine children with achondroplasia with respiratory complications resulting from one of four mechanisms: chest deformity, upper airway obstruction and sleep-disordered breathing, coinci-
The Journal of Pediatrics March 1984
dental chronic pulmonary conditions, and neurologic complications. Evidence for any of the first three mechanisms was absent in our patients, whose symptoms resolved after decompressive craniectomy/laminectomy. Yang et al.~ described the pathologic findings in two infants with achondroplasia. Each had a small foramen magnum and evidence of severe damage to the corresponding segment of the upper cervical cord. One newborn baby had respiratory failure; the other died of cardiopulmonary complications at age 6 months. In the first patient, the brainstem was located abnormally posterior to the foramen magnum, causing the upper cervical cord and lower medulla to be angulated anteriorly. Findings on examination of the second patient were unremarkable. Both patients evidenced central gray matter necrosis comparable to that seen following traumatic hyperextension injuries. In our patient 3, microscopic examination of the cord showed a gliotic area with cystic degeneration; the cyst was lined with dysplastic cells. This cervical lesion was the presumed reason this patient died despite foramen magnum decompression. The possibility of cervical cord compression must be considered in young achondroplastic patients with respiratory abnormalities, especially in those who do not have abnormal thoraces, upper airway obstruction, or chronic pulmonary disease. Failure to consider cord compression may result in undue delay before the correct diagnosis is made and corrective surgery performed. Hyperextension of the neck should be avoided whenever possible in achondroplastic patients. It is recognized that all infants with achondroplasia have a small foramen magnum. In one of our patients, prolongation of SER latencies was consistent with cord compression. Data are insufficient to be certain whether SERs alone can be relied on to demonstrate cord compression in achondroplastic children. Cord. compression can be confirmed by CT scans 9f the foramen magnum and upper cervical cord. Surgery should be performed at the first sign of cord compression, as results are poor after extensive damage has occurred. ltydrocephalus is often present in achondroplastic patients of normal intelligence. One theory attributes the hydrocephalus to premature synostoses of the base of the skull, producing obstruction of the ventricular fluid circulation, with internal hydrocephalus. In both of our patients, CT scans after occipital craniectomy showed no decrease in ventricular size. This argues against obstruction at the base of the skull as the cause of their hydrocephalus. REFERENCES I. Langer LO, Baumann PA, Gorlin RJ: Achondroplasia: Clinical radiological features with comment on genetic implications. Clin Pediatr 7:474, 1968.
Volume 104 Number 3
2. Cohen ME, Roscnthal AD, Matson DD: Neurological abnormalities in achondroplastic children. 3 PEDIATR 71:367, 1967. 3. Plum F, Posner J: Diagnosis of stupor and coma. Philadelphia, 1971, FA Davis, p 29. 4. Haymaker W: Bing's local diagnosisin neurologicdisease. St. Louis, 1969, CV Mosby, p 100. 5. Collmann B: Beitag zur Kenntniss der Chondrodystrophia foctalis. Virchows Arch [Pathol Anat] 166:1, 1901.
Clinical and laboratory observations
401
6. Yamada H, Makamura S, Tajima M, Kageyama N: Neurological manifestations of pediatric achondroplasia. J Neurosurg 54:49, 1981. 7. Stokes DC, Phillips JA, Leonard CO, et al: Respiratory complications of achondroplasia. J PEDIA'rR102:534, 1983. 8. Yang SS, Corbett DP, Brough AJ, lteidelberger KP: Upper cervical myelopathy in achondroplasia. Am J Clin Pathol 68:68, 1977.
Superiority o f acridine orange stain versus Gram stain in partially treated bacterial meningitis Martin B. Kleiman, M.D., Janet K. Reynolds, M.S., Nancy H. Watts, M.S., Richard L. Schreiner, M.D., and James W. Smith, M.D. Indianapolis, Ind.
GRAM STAIN EXAMINATION of cerebrospinal fluid often yields rapid, reliable information that is useful in selecting initial antimicrobial therapy for the patient with bacterial infection. Although partial antibiotic treatment may not obscure the cellular changes typical of purulent meningitis, suboptimal treatment can sterilize the CSF, decrease the number of bacteria present, or alter bacterial cell wall structure and function sufficiently to render the Gram stain negative or misleading) Acridine orange [3,6-bis(dimethylamino)acridine] is a lluorochrome that stains the nucleic acids of somatic cells,2 bacteria) and other microorganisms?.: KronvalP first observed that bacteria stained bright orange and the background of cell debris and human cells appeared yellow to pale green when the stain pH was maintained at 3.5 to 5.0, thereby permitting easy identification of bacteria in clinical specimens. The acridine orange stain has been used for detecting malarial parasites in human blood smears, ~.6 gonococci in urethral smears, ~and Trichomonas vaginalis ~ in vaginal secretions. McCarthy and Senne" found the AOS as sensitive as
From the Department of Pediatrics. Sections of Infectious Disease attd Neonatology, and the Department of Pathology, Division of Microbiolog)', Indiana University School of Medicine. Supported by a grant from the Riley Memorial Association. Presented in part at the annual meetings of the Society for Pediatric Research, Washington. D.C.. May 5. 1983. attd the American Academy of Pediatrics, San Francisco, October 24, 1983. Reprint requests: Martin B. Kleiman. M.D.. Section of b:fectious Disease. Department of Pediatrics. James IVhitcomb Riley Hospital for Children. 702 Barnhill, Indianapolis, IN 46223.
subculture for detecting organisms in blood culture bottles that did not demonstrate visible growth after 24 hours. Mirrett et al. 9 found the AOS more sensitive and equally as specific as the Gram and methylene blue stains for early detection of positive blood cultures. Lauer et al) ~ compared the AOS and Gram stains of'direct smears of 487 specimens of body fluids, tissues, and exudates and concluded that the AOS and Gram stain were equally specific, whereas the AOS was slightly more sensitive. Eisenach et
AOS
Acridine orange stain
]
al." examined 14 culture-positive CSF samples and found the AOS positive in 10 and the Gram stain positive in eight. The objectives of our investigation were to compare (1) the sensitivity of the AOS and Gram stain for detecting bacteria in direct smears of CSF obtained before and at intervals during antibiotic treatment, and (2) Gram stain and AOS with culture of CSF obtained during antibiotic treatment. MATERIALS AND METtIODS Cerebrospinal fluid was obtained from 217 children undergoing diagnostic lumbar or ventricular taps between March 1981 and April 1983. All 32 patients with infections caused by Haemophilus influenzae, Neisseria meningitidis, or Streptococcus pneumoniae were between 3 months and I0 years of age. Ten of I1 patients with meningitis caused by group B streptococcus, Streptococcus faecalis, Staphylococcus aureus, Escherichia coli, or