Incomplete Alpha Coma Pattern in a Child

Case Reports

Incomplete Alpha Coma Pattern in a Child Rajesh RamachandranNair, MD and Shelly Karen Weiss, MD Only 19 cases of alpha coma pattern in the pediatric age group had been reported. Recently the concept of reactivity has been included in the definition of alpha coma. Electroencephalography reveals reactivity to painful stimuli in incomplete alpha coma. In adults, this pattern has a better prognosis than the complete pattern with no reactivity. A 5-year-old child had coma secondary to hypoxic brain damage after surgery. His electroencephalogram documented an incomplete alpha coma pattern. He remained in a vegetative state. This study is the first report of a child with incomplete alpha pattern documented on electroencephalogram. © 2005 by Elsevier Inc. All rights reserved. RamachandranNair R, Weiss S. Incomplete Alpha Coma Pattern in a Child. Pediatr Neurol 2005;33:127-130.

Introduction Alpha coma and alpha-frequency coma are terms used to refer to an electroencephalographic pattern predominating in the alpha frequency band (8-12 Hz) and present in unresponsive patients [1,2]. In the literature approximately 360 cases of alpha coma were described from 1974 to 1998 [2]. Only 19 cases of alpha coma in the pediatric age group were reported in English-language indexed journals during the period 1975 to 2003 [1,3-12]. The etiologies included cardiorespiratory arrest, head trauma, brainstem lesions, and toxic-metabolic abnormalities. Complete alpha pattern is described as a frontally dominant or diffuse invariant pattern with no reactivity to external stimulation

From the Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Canada.

© 2005 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2005.01.015 ● 0887-8994/05/$—see front matter

[2,13]. Recently many authors have extended the alpha coma concept to include reactive electroencephalographic patterns and other frequencies (theta) [2,13,14]. Incomplete alpha coma is characterized by posteriorly dominant alpha frequency, which indicates reactivity to external stimuli [2,13]. To our knowledge, incomplete alpha coma pattern in children has not been reported before. This study presents the case of a 5-year-old male who demonstrated an incomplete alpha coma pattern in the electroencephalogram after hypoxic-ischemic brain injury secondary to cardiorespiratory arrest.

Case Report A 5-year-old male was admitted to the critical care unit of our hospital 2 hours after cardiorespiratory arrest. He underwent tonsillectomy with adenoidectomy under general anesthesia at another hospital. In the postoperative period he required reintubation for postextubation apnea. During intubation he developed cardiac asystole, which was reverted with intravenous atropine and adrenaline. An emergency bronchoscopy retrieved adenoid tissue from the right main bronchus. After the resuscitation, he had two generalized tonic-clonic seizures, which were managed with intravenous phenytoin and phenobarbital. On arrival, he was comatose with a Glasgow Coma Scale score of 3. Pupils were 4 mm bilaterally with sluggish reaction to light. Corneal and gag reflexes could be elicited. Doll’s eye movement was partially preserved. All the deep tendon reflexes were sluggish, and the plantar response was extensor on both sides. He had a heart rate of 104/minute, and the blood pressure was 96/70 mm Hg. Blood gas analysis indicated metabolic acidosis, which was corrected. Hemogram, renal and liver functions, serum calcium, magnesium, and glucose were within normal range. Five hours after the onset of coma, he developed generalized myoclonic jerks. The first electroencephalogram (Stellate-Rhythm version 9.0 software) performed in the pediatric intensive care unit 7 hours after cardiorespiratory arrest (CRA) disclosed generalized periodic epileptiform discharges at an interval of 1.5 to 4 seconds on a diffusely attenuated background. There was no reactivity to painful stimuli. Scalp electrodes were placed according to the International 10-20 system with Pz

Communications should be addressed to: Dr. RamachandranNair; Division of Neurology; The Hospital for Sick Children; University of Toronto; 555 University Avenue; Toronto M5G 1X8, Canada. Received October 19, 2004; accepted December 10, 2004.

RamachandranNair and Weiss: Incomplete Alpha Coma Pattern 127

Figure 1. Electroencephalogram on the second day revealed frontally dominant alpha frequency, which attenuated in voltage to painful stimulus. The period of voltage attenuation is observed between the two arrowheads.

as standard reference. Filters were set at 1 and 70 Hz, and the sampling rate was 200 Hz. Serum phenytoin level was 64 ␮mol/L (normal value 40-80) and phenobarbital was 170 ␮mol/L (normal value 65-170). After 24 hours, there was no improvement in the neurologic status. A repeat electroencephalogram (performed at 26 hours after arrest) documented frontally dominant 9.5 to 10 Hz rhythm, intermixed with intermittent theta and delta activity. This pattern was consistent both in the referential and bipolar montages. The frontally dominant alpha frequency rhythm was continuous during the 30-minute record. It lacked the typical waxing and waning morphology of the physiologic alpha rhythm. However, the voltage attenuated to painful stimuli applied by pinching the nail bed of the right index finger (Fig 1). Reactivity was confirmed by repeating the same stimulus once more. There was absent cortical response to bilateral median sensory stimulation. Visual evoked potentials were absent on both sides. Brainstem auditory evoked response was normal bilaterally. Repeat electroencephalogram on the third and sixth day revealed complete replacement of the alpha frequency with polymorphic delta activity, which indicated no reactivity. Repeat evoked potential studies on the sixth day were unchanged. Computed tomographic scan of the brain performed at 48 hours revealed diffuse white matter and basal ganglia lucencies suggestive of hypoxic brain damage. He remained in a coma for 6 weeks. He remains in a vegetative state 12 weeks after the onset of coma. The last electroencephalogram, taken at 12 weeks, disclosed diffuse polymorphic delta activity. Discussion Complete neurologic recovery has been reported in children with complete alpha coma [3,6,9,11]. However, out of 360 cases, only 2 adults had a normal neurologic

128

PEDIATRIC NEUROLOGY

Vol. 33 No. 2

function after complete alpha coma [2,7,15]. Recent studies have indicated that presence of electroencephalographic reactivity correlated with survival, though many of these survivors manifested varying grades of neurologic impairment [2, 13]. In a study of 14 adult patients with postanoxic alpha coma, all patients with complete alpha coma died. Three of five patients with incomplete alpha coma survived [13]. Reactivity could be in the form of attenuation or increase in alpha frequency pattern or an increase/decrease in the amount of theta and delta frequency activity [2] In this child, encephalopathy was secondary to cardiorespiratory arrest, which was documented by electrocardiogram. The causes of coma in the 19 children who manifested alpha coma pattern are summarized in Table 1. The causes included cardiorespiratory arrest (10), head injury (2), drug intoxication (2), seizure (1), metabolic (1), infection (1), tumor (1), and stroke (1). The youngest age at which alpha coma was reported is 2 months (Patient 5) [5]. All these children were reported to have a complete alpha coma pattern. Ten (52.6%) children died, five had normal neurologic status or returned to pre-event status and four manifested severe neurologic deficits. Six of the 10 children with cardio-respiratory arrest died. Only one child with cardio-respiratory arrest had a normal neurologic outcome. As in adults, the survival was better if the cause of alpha coma was drug toxicity, stroke, or infection. One child with cyclosporin toxicity expired after a cardiac arrest [12]. Alpha coma pattern is a transient phenomenon. It has been reported to be present as early as 2 hours after a cardio-respiratory arrest and as late as 5 days after onset of coma [9,15]. Spindle coma has been reported as late as 11 days [9]. In the child described in the present study, alpha coma pattern developed on the second day. As the child was not on continuous electroencephalographic monitor-

Table 1.

Alpha coma pattern in children

No.

Reference

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

Westmoreland [1] Lersch [3] Lersch Yamada [4] Homan [5] Pulst [6] Sorensen [7] Molofsky [8] Horton [9] Horton Horton Horton Horton Horton Frisher [10] Frisher Frisher Collins [11] Sarma [12]

Age 14 3 15 2 2 13 16 12 2 2 2 4 8 12 6 11 5 22 3

yr yr yr yr mo yr yr yr yr yr yr yr yr yr yr yr yr mo yr

Cause of Alpha coma CPA Status epilepticus Head Injury Reye’s syndrome Drowning Imipramine toxicity CPA Cardiac arrest Drowning Head injury Drowning Viral encephalitis Thalamic tumor Stroke in SCD Drowning Drowning CPA Strangulation Cyclosporin toxicity in RF

Outcome Death Survived–Normal Survived–Severe disability Death, D3 Death Survived–Normal Survived–Impaired memory Survived–Ataxia, LD Death, D4 Death, D11 Death, D5 Survived–Normal Death Survived (Returned to premorbid state) Death, D21 Death, D11 Survived–PVS Survived–Normal Death following cardiac arrest

Abbreviations: CPA ⫽ Cardiopulmonary arrest D ⫽ Day LD ⫽ Learning disability PVS ⫽ Persistent vegetative state RF ⫽ Renal failure SCD ⫽ Sickle cell disease

ing, one can assume that alpha coma developed between 7 hours and 48 hours after the arrest. Persistence of rhythmic coma in children is associated with a poor outcome [9]. Alpha frequency was posteriorly dominant in all the cases of incomplete alpha coma reported so far. In the present case, the alpha frequency was more prominent in the anterior head region. Computed tomographic scan of the brain revealed significant hypoxic damage in the posterior head region. This condition might have resulted in poor expression of alpha frequency in the posterior region. The exact brain generator of alpha frequency in coma is not clear. Many authors believe that alpha-frequency coma represents a de novo abnormal pattern. In dogs, after exsanguination and resuscitation, posthypoxic alpha-like activity appears first with maximum amplitude in the amygdala. This activity could be blocked by bilateral obliteration of the amygdala, but not by destruction of cerebral hemispheres [2,13]. After hypoxic injury in humans, amygdala, hypothalamus, brainstem, and forebrain structures are relatively preserved [2,13]. Once thalamocortical neurons are damaged, the amygdala or other subcortical structures may function as the pacemaker of electric brain activity. Berkhoff et al. had postulated that incomplete alpha coma might, in some patients, represent a residuum of physiologic alpha electroencephalographic activity [13]. If incomplete alpha coma pattern represented a residuum of physiologic alpha activity, the electroencephalogram should have revealed a well-modulated alpha or at least persistence of alpha on follow-up. In our child, the subsequent electroencephalograms documented dif-

fuse polymorphic delta activity. This case and the occurrence of alpha coma in a 2-month-old infant uphold the de novo theory that alpha frequency in alpha coma pattern did not evolve from physiologic alpha rhythm. Incomplete alpha coma may represent a less severe hypoxic damage, but most likely, it is a de novo transient abnormal rhythm. Electroencephalography combined with somatosensory evoked potential study has better prognostic significance in postanoxic coma than either test alone. A meta-analysis of 41 studies, which looked into the role of somatosensory evoked potentials performed early after onset of coma in predicting the likelihood of nonawakening, demonstrated that 93% of children with bilaterally absent cortical responses in somatosensory evoked potentials died or remained in persistent vegetative state [16]. The child described herein had a consistently absent cortical response. He remained in a vegetative state. Electroencephalographic reactivity alone may not predict a good outcome as in this child. Persistently abnormal electroencephalographic background activity and absent cortical responses are also equally important in predicting the outcome after hypoxic coma. Conclusion Incomplete alpha coma is a previously described electroencephalographic pattern, which represents an abnormal transient de novo pattern. This study is the first report of incomplete alpha coma pattern in the pediatric age group. The distribution of the alpha frequency in incom-

RamachandranNair and Weiss: Incomplete Alpha Coma Pattern 129

plete alpha coma pattern need not be in the posterior head region as reported before. In this child, alpha frequency was more frontally dominant. Early and serial electroencephalographic studies after acute hypoxic insult may be important to demonstrate this pattern in children. Prognosis of postanoxic alpha coma in children is better than in adults in terms of survival. Electroencephalographic reactivity in adults with alpha coma is associated with a relatively better outcome. However, the value of electroencephalographic reactivity in alpha coma pattern in the prognosis of pediatric coma is yet to be determined. References [1] Westmoreland BF, Klass DW, Sharbrough FW, Reagan TJ. Alpha-coma: Electroencephalographic, clinical, pathologic, and etiologic correlations. Arch Neurol 1975;32:713-8. [2] Kaplan PW, Genoud D, Ho TW, Jallon P. Etiology, neurologic correlations, and prognosis in alpha coma. Clin Neurophysiol 1999;110: 205-13. [3] Lersch DR, Kaplan AM. Alpha-pattern coma in childhood and adolescence. Arch Neurol 1984;41:68-70. [4] Yamada T, Stevland N, Kimura J. Alpha-pattern coma in a 2-year-old child. Arch Neurol 1979;36:225-7. [5] Homan RW, Jones MG. Alpha-pattern coma in a 2-month-old child. Ann Neurol 1981;9:611-3.

130

PEDIATRIC NEUROLOGY

Vol. 33 No. 2

[6] Pulst SM, Lombroso CT. External ophthalmoplegia, alpha and spindle coma in imipramine overdose: Case report and review of the literature. Ann Neurol 1983;14:587-90. [7] Sorensen K, Thomassen A, Wernberg M. Prognostic significance of alpha frequency EEG rhythm in coma after cardiac arrest. J Neurol Neurosurg Psychiatry 1978;41:840-2. [8] Molofsky WJ. Alpha coma in a child. J Neurol Neurosurg Psychiatry 1982;45:95. [9] Horton EJ, Goldie WD, Baram TZ. Rhythmic coma in children. J Child Neurol 1990;5:242-7. [10] Frisher S, Herishanu Y. Mu and alpha rhythm in comatose children. Childs Nerv Syst 1985;1:208-10. [11] Collins AT, Chatrian GE. EEG rhythm of alpha frequency in a 22-month-old child after strangulation. Neurology 1980;30:1316-9. [12] Sarma GR, Kumar A, Roy AK, Pinheiro L. Post-cardiorespiratory arrest beta-alpha coma: An unusual electroencephalographic phenomenon. Neurol India 2003;51:266-8. [13] Berkhoff M, Donati F, Bassetti C. Postanoxic alpha (theta) coma: A reappraisal of its prognostic significance. Clin Neurophysiol 2000;111:297-304. [14] Young GB, Blume WT, Campbell VM, et al. Alpha, theta and alpha-theta coma: A clinical outcome study utilizing serial recordings. Electroencephalogr Clin Neurophysiol 1994;91:93-9. [15] Iragui VJ, McCutchen CB. Physiologic and prognostic significance of “alpha coma”. J Neurol Neurosurg Psychiatry 1983;46:632-8. [16] Robinson LR, Micklesen PJ, Tirschwell DL, Lew HL. Predictive value of somatosensory evoked potentials for awakening from coma. Crit Care Med 2003;31:960-7.