Correspondence

Case 12-2008: Apnea and Seizures in a Newborn Infant

N Engl J Med 2008; 359:315-316July 17, 2008

Article

To the Editor:

Redline et al. (April 17 issue)1 discuss an interesting case of a newborn with seizures and apnea secondary to perinatal ischemic stroke. Although an accurate diagnosis was made without the use of lumbar puncture and cerebrospinal fluid analysis, we think these tests should have been performed.

As the authors state, intracranial hemorrhage, especially subarachnoid hemorrhage, is a common cause of neonatal seizures. Although a computed tomographic (CT) scan of the head showed no evidence of subarachnoid hemorrhage, small subarachnoid hemorrhages are often diagnosed only with cerebrospinal fluid analysis.

In addition, as the authors mention, meningitis is a possibility, especially given maternal chorioamnionitis. Although blood cultures were negative, blood cultures may be negative in neonates with documented bacterial meningitis.2,3 Herpes simplex virus (HSV) meningitis is another possibility. Despite no maternal history of HSV infection, the temporal-lobe hypodensity on the CT scan mandates its consideration.

Retrospectively, although cerebrospinal fluid analysis was not required to make the correct diagnosis, we believe the authors should have emphasized that in the workup of a neonate with seizures and apnea, lumbar puncture should be strongly considered.

Shiwan K. Shah, D.O.
Sunil Jain, M.D.
Joan Richardson, M.D.
University of Texas Medical Branch, Galveston, TX 77555
skshah@utmb.edu

3 References

1. 1

   Case Records of the Massachusetts General Hospital (Case 12-2008). N Engl J Med 2008;358:1713-1723
   Full Text | Web of Science | Medline

2. 2

   Garges HP, Moody MA, Cotten CM, et al. Neonatal meningitis: what is the correlation among cerebrospinal fluid cultures, blood cultures, and cerebrospinal fluid parameters? Pediatrics 2006;117:1094-1100
   CrossRef | Web of Science | Medline

3. 3

   Nel E. Neonatal meningitis: mortality, cerebrospinal fluid, and microbiological findings. J Trop Pediatr 2000;46:237-239
   CrossRef | Web of Science | Medline

To the Editor:

Redline and colleagues do not mention possible maternal cocaine use and consequent fetal exposure to the drug as a possible risk factor for perinatal stroke. The maternal history neither included nor excluded this important risk factor. A neuroradiologic study1 showed that 17% of newborns who had been exposed in utero to cocaine had cerebral infarction, as compared with 2% of newborns in the control group. In particular, the authors postulated that the significantly higher frequency of stroke among the newborns who had been exposed in utero was related to vasospasm caused by cocaine when used in the third trimester of pregnancy. Even though perinatal stroke is considered to be a multiple-risk-factor disease,2 cocaine abuse during pregnancy is the only risk factor that is 100% preventable. Physicians should therefore emphasize the potentially adverse effects of drug abuse in any pregnancy.

Ruggero Spadafora, M.D.
University of California, San Francisco, San Francisco, CA 94143
ruggero.spadafora@ucsf.edu

2 References

1. 1

   Heier LA, Carpanzano CR, Mast J, Brill PW, Winchester P, Deck MD. Maternal cocaine abuse: the spectrum of radiologic abnormalities in the neonatal CNS. AJNR Am J Neuroradiol 1991;12:951-956
   Web of Science | Medline

2. 2

   Wu YW, Lynch JK, Nelson KB. Perinatal arterial stroke: understanding mechanisms and outcomes. Semin Neurol 2005;25:424-434
   CrossRef | Web of Science | Medline

Author/Editor Response

In response to the comments by Shah et al.: we did not overlook the need for lumbar puncture in this patient. Lumbar puncture should be a part of the workup for neonatal seizures, including apneic seizures. However, there are clinical situations in which the cause is obvious, in which case, a lumbar puncture may not be necessary. Since the diagnosis of an infarct of the middle cerebral artery was made expeditiously by means of a magnetic resonance imaging (MRI) scan of the brain, we decided to defer a lumbar puncture. We considered the possibility of HSV encephalitis on the basis of a hypodense lesion on the CT scan. However, the subsequent MRI of the brain made this possibility unlikely.

In our opinion, the utility of cerebrospinal fluid analysis is limited in the diagnosis of neonatal subarachnoid hemorrhage with a negative CT brain scan, because of the confusing cerebrospinal fluid composition in neonates, who normally have xanthochromia (derived from bilirubin), a high cerebrospinal fluid protein level (related to gestation), and a variable number of red cells (presumably derived from leakage of meningeal capillaries during delivery).1 The use of cerebrospinal fluid analysis (to look for xanthochromia and red cells) for the diagnosis of subarachnoid hemorrhage with a negative CT scan is more applicable to adults in whom the source of bleeding is arterial, often from a leaking aneurysm.

In response to Spadafora, we agree that screening for cocaine or other forms of drug abuse may be appropriate in many cases of perinatal stroke. We did not screen the mother in this case because we considered her to be at low risk. The presence of overt thrombosis in this case (heart valve and placenta), moreover, differs from that which is usually seen in perinatal stroke from cocaine abuse. Although it is well recognized that cocaine causes arterial vasoconstriction,2 and although many consider the mechanism of perinatal stroke caused by cocaine to be cerebral vasospasm,3 clear documentation of venous thrombosis due to cocaine abuse is lacking.4 In this case, venous thrombosis was the presumed pathway because of the placental pathology, valvular thrombosis, and patent foramen ovale with right-to-left shunt.

Kalpathy S. Krishnamoorthy, M.D.
Eric F. Grabowski, M.D., D.Sci.
Drucilla J. Roberts, M.D.
Massachusetts General Hospital, Boston, MA 02114

4 References

1. 1

   Volpe JJ. Neurology of the newborn. 4th ed. Philadelphia: W.B. Saunders, 2001.
   

2. 2

   Madden JA, Konkol RJ, Keller PA, Alvarez TA. Cocaine and benzoylecgonine constrict cerebral arteries by different mechanisms. Life Sci 1995;56:679-686
   CrossRef | Web of Science | Medline

3. 3

   Heier LA, Carpanzano CR, Mast J, Brill PW, Winchester P, Deck MD. Maternal cocaine abuse: the spectrum of radiologic abnormalities in the neonatal CNS. AJNR Am J Neuroradiol 1991;12:951-956
   Web of Science | Medline

4. 4

   Wright NM, Martin M, Goff T, Morgan J, Elworthy R, Ghoneim S. Cocaine and thrombosis: a narrative systematic review of clinical and in-vivo studies. Subst Abuse Treat Prev Policy 2007;2:27-27
   CrossRef | Medline