days of treatment." The predictable period of high risk between 40 and 100 days from initiation of chemotherapy
Attack Rate of Pneumocystis carinii Pneumonitis (PCP) in Children Receiving Treatment for Acute Lymphatic Leukemia
Treatment No TMP-SMZ High-dose brief TMP-SMZ* Placebo (Hughes et
Patients With PCP
al'0)
Low-dose contin¬ uous TMP-SMZ (Hughes et al'°)t
'Compared =
2
no
4.15,
with =
0.02.
was
the basis for
17
80
0
80
pattern since
their infections occurred randomly
throughout the entire period of treat¬
ment. This difference may be related to the intensity of therapy at differ¬ ent phases of the disease. Both
Hughes' and our group have noted the correlation of increased PCP with the addition of more intense chemothera¬ py/'2
TMP-SMZ, x2
=
Since the incidence of PCP in
.357,
high-dose
TMP-SMZ,
Disease Control noted an association between the length of hospitalization and development of pneumocystis pneumonia. In addition, a greater percentage of hematology staff, com¬ pared with other hospital staff, were seropositive for pneumocystis anti¬ bodies. Both observations suggest hos¬ pital transmission of the organism/ Recent animal studies confirm the spread of pneumocystis organisms by horizontal transmission." The results by Hughes et al·" employing a lower dose of TMP-SMZ (TMP 4 mg and SMZ 20 mg/kg/day) during the entire period of chemo¬ are
group
not conform to this
Patients Without PCP 13
Failure of patient compliance is unlikely because all oral medications were given with nursing supervision in the clinic or parent care facility. During our institutional outbreak of PCP, investigation by the Center for
therapy
our
initiating the prophylaxis program at four weeks. Hughes's patients did
0.28.
tCompared =
with
4
in
clearly superior
to
our
results. Comparison of results be¬ tween the placebo and treated group in Hughes's series and between the no TMP-SMZ group and treated group in our series shows the superiority of long-term low-dose TMP-SMZ (Ta¬ ble). The attack rate of the groups who did not receive effective prophylaxis are quite similar: 17 of 80 (21%) of Hughes's placebo group compared with four of 17 (23%) of our nontreated group but, the time of onset of PCP differed. Our patients conform more to the general experi¬ ence of the investigators of the Chil¬ dren's Cancer Study Group \vho noted that the greatest frequency of pulmo¬ nary infections in 569 patients with ALL occurred within the first 100
8. Ruebush TK, Weinstein RA, Baehner RL, et al: An outbreak of pneumocystis pneumonia in children with acute leukemia. Am J Dis Child, to be published. 9. Walzer PD, Schnelle V, Armstrong D, et al: Experimental transmission studies of Pneumocystis carinii in nude mice. Science 197:177-179, 1977. 10. Hughes W, Kuhn S, Chaudhary S, et al: Successful chemoprophylaxis for Pneumocystis carinii pneumonitis. Pediatr Res 11:501, 1977. 11. Siegel SE, Baehner RL, Nesbitt M: Pulmonary disease during the therapy of childhood acute lymphocytic leukemia. Abstracts American Society of Hematology, 1974. 12. Hughes WT, Feldman S, Aur RJ, et al: Intensity of immunosuppressive therapy and the incidence of Pneumocystis carinii pneumonitis. Cancer 36:2004-2009, 1975.
our
patients who received TMP-SMZ was not decreased, but simply delayed in onset for a period up to 170 days after initiation of chemotherapy and the rate of PCP in our non-ALL patients increased to 17%, we have abandoned the short-term high-dose TMP-SMZ as prophylaxis and are now evaluating the efficacy of low dose continuous TMP-SMZ for all our patients at LAWRENCE J. WOLFF, MD ROBERT L. BAEHNER, MD Department of Pediatrics Indiana University School of Medicine James Whitcomb Riley Hospital for Children Indianapolis, IN 46202 This investigation was supported by grant IN\x=req-\ 450 awarded by the American Cancer Society and by a grant from the James Whitcomb Riley Memorial Association. 1. Stevens DA: Current concepts in cancer: II. Infections in cancer patients. Int J Radiat Oncol Biol Phys 1:295-296, 1976. 2. Simone JV, Holland E, Johnson W: Fatalities during remission of childhood leukemia. Blood 39:759-770, 1972. 3. Hughes WT, Feldman S, Sanyal SK: Treatment of Pneumocystis carinii pneumonitis with trimethoprim-sulfamethoxazole. Can Med Assoc J 112:47S-50S, 1975. 4. Hughes WT, Feldman S, Chaudhary S, et al: Comparison of trimethoprim-sulfamethoxazole and pentamidine in the treatment of Pneumocystis carinii pneumonitis. Pediatr Res 10:399, 1976. 5. Lau WK, Young LS: Trimethoprim-sulfamethoxazole treatment of Pneumocystis carinii pneumonia in adults. N Engl J Med 295:716-718, 1976. 6. Wolff LJ, Bartlett MS, Baehner RL, et al: The causes of interstitial pneumonitis in immunocompromised children: An aggressive systematic approach to diagnosis. Pediatrics 60:41-45, 1977. 7. Hughes WT, McNabb PC, Makres TD, et al: Efficacy of trimethoprim and sulfamethoxazole in the prevention and treatment of Pneumocystis carinii pneumonitis. Antimicrob Agents Chemother 5:289-293, 1974.
Association of Prune Belly Syndrome and Gastroschisis
Prune belly and gastroschisis are syndromes that have been well described in the literature. Prune belly or the "triad syndrome" is composed of cryptorchidism, deficiency of the abdominal wall, musculature, and urinary tract abnormalities.1
-4 Gastroschisis is a congenital full-thickness cleft in the abdominal wall, usually to the right of a normally inserting umbilical cord, and evisceration through the defect with no overlying membrane.5 -8 There have been more than 200 cases of prune belly and greater than 120 cases of gastroschisis reported in the literature, but the two syndromes have not, to our knowledge, been described together in the same patient. This report describes a patient with both prune belly syndrome and gastroschisis.
Report of a Case.\p=m-\Thisinfant was deliva gravida 9, para 7, 37-year-old woman on June 23, 1976 in Chicago Osteopathic Hospital. Excessive maternal alcohol consumption was the only complication of pregnancy. A previous child with spina bifida and hydrocephalus had died at the age of 2 years. Labor began at 36 weeks by dates and lasted two hours with membrane rupture occurring one hour prior to deliv¬ ery. No systemic or local anesthetics were administered and the delivery was sponta¬ neous vaginal. Apgar scores were 3 and 4 at one and five minutes respectively, and the patient required resuscitation for 15 min¬ utes. A large defect in the abdominal wall with evisceration was noted in the delivery room. The patient was transferred to the Wyler Children's Hospital Intensive Care Nursery. On examination, the patient was in no distress and weighed 2,165 gm. The Dubo¬ witz score indicated a gestational age of 37 ered from
weeks. There was a 6-cm defect in the abdominal wall to the right of a normal
Downloaded From: http://archpedi.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/31/2015
umbilical cord through which the stomach, the entire small intestine, and two-thirds of the colon protruded. There was a midgut malrotation. Only minimal thickening of the bowel wall was present. The abdominal wall musculature, on examination and
subsequently The scrotal
at surgery,
was
hypoplastic.
sac was small and the testes not palpable. There were supernu¬ merary digits on each hand and anonychia
were
of the pollicis and hallucis bilaterally. The remainder of the physical examination was unremarkable. At 2 hours of age the first stage of a twostage closure was performed employing a silastic pouch to cover the defect according to the method devised by Schuster." Ladd's bands were dissected and gastrostomy was performed. Postoperatively the patient's condition was managed with a pressure ventilator, antibiotics, and peripheral par¬ enteral nutrition. Complications included a urinary fistula probably involving the urachus, a wound cellulitis with subsequent fecal fistula, and two urinary tract infec¬ tions. The cystogram showed a small, irregular bladder with reflux into markedly dilated ureters and calyceal systems bilaterally. There was evidence of bilateral loss of renal cortex. The urethra appeared normal on the voiding films. There was no evidence of posterior urethral valves. The intravenous pyelogram demonstrated a dilated pelvocalyceal system on both sides. At 11 weeks of age the patient was discharged from the hospital weighing 2,175 gm and taking feedings by mouth ad lib. He had normal stools and spontaneous sterile urine production. The BUN and creatinine levels were 6.0 mg/100 ml and 0.3 mg/100 ml, respectively. Chromosome studies were normal. At 7 months of age, when most recently seen, clinically his urinary and bowel func¬ tion continued to be normal.
Comment.—Gastroschisis is theo¬ rized to result from a failure of local¬ ized differentiation and subsequent résorption of embryonic mesenchyme in one of the two lateral folds of mesenchyme in the abdominal wall. Subsequently, the ectoderm also invo¬ lutes, leaving a full-thickness abdom¬ inal wall cleft. The defect is unilateral and originates during the latter part of the third week of embryonic life.5 Ives' has proposed that the prune belly syndrome is caused by a localized abnormality of the mesoderm during the time of the initial formation of the primitive streak and its outflow of mesoderm early in the third week of development. A defect in the paraxial mesoderm would account for the abdominal wall deficiency. The inter¬ mediate mesoderm deficiency would explain the renal abnormalities in the
musculature of the ureters, bladder and gubernaculum, accounting for megalometers, megacystis and failure of descent of the testes respectively. This case report describing a pa¬ tient with both gastrochisis and prune belly supports Ives' hypothesis. One case report exists of a patient with both prune belly and omphalocele.4 Omphalocele is also thought to be the result of a defect during the last part of the third embyronic week, provid¬ ing supporting evidence for the hypo¬ thesis.
CRAIG WILLERT, MD HOWARD COHEN, MD
YA-MEI T. Yu, MD JOHN D. MADDEN, MD Pritzker School of Medicine of The University of Chicago Department of Pediatrics 950 E 59th St
Chicago,
IL 60637
1. Eagle JF, Barrett GS: Congenital deficiency of abdominal musculature with associated genito-urinary abnormalities: A syndrome, report of nine cases. Pediatrics 6:721-736, 1950. 2. Rogers LW, Ostrow PT: The prune belly syndrome: Report of 20 cases and description of a lethal variant. J Pediatr 83:786-793, 1973. 3. Ives EJ: The abdominal muscle deficiency triad syndrome\p=m-\Experiencewith ten cases. Birth Defects: Original Article Series, No. 4, vol 10, pp 127-135, 1974. 4. Cremin BJ: The urinary tract anomalies associated with agenesis of the abdominal walls. Br J Radiol 44:767-772, 1971. 5. Lewis JE, Kraeger RR, Danis RK: Gastroschisis. Arch Surg 107:218-222, 1973. 6. Gilbert MG, Mencia LF, Puranik SR, et al: Management of gastroschisis and short bowel: Report of 17 cases. J Pediatr Surg 7:598-607, 1972. 7. Mahour GH, Weitzman JJ, Rosenkrantz JG: Omphalocele and gastroschisis. Ann Surg 177:478-482, 1973. 8. Moore TC: Gastroschisis with antenatal evisceration of intestines and urinary bladder. Ann Surg 158:263-269, 1963. 9. Schuster SR: A new method for the staged repair of omphalocele. Surg Gynecol Obstet 125:837, 1967.
Dyskinesia and Akathisia Induced by Ethosuximide Ethosuximide (Zarotin)
was introduced in 1958 for the treatment of petit mal epilepsy' and has since been found useful in the control of minor motor seizures. We report the case histories of two children in whom a syndrome characterized by motor restlessness (akathisia) and purposeless movements of the tongue, jaw, face, and extremities (dyskinesia) developed 12 hours after the first ingestion of ethosuximide. Among the various side effects attributed to this drug, this reaction must be exceed-
ingly rare as we have been able to find only one previous report.2 Report of Cases.\p=m-\Case1.\p=m-\Thepatient developing normally and was in good
was
health, when at the age of 8 months, a prolonged generalized seizure occurred in association with
a
fever of 38 C. Phenobar-
bital, diazepam, and paraldehyde were given. His physical examination was normal afterwards, as were blood chemistries, spinal fluid, and roentgenogram of
the skull. An EEG revealed suppression of the background activity in the right hemisphere. Despite the use of phénobarbital he had ten more seizures during the next six months. Phenytoin was tried but not found useful. At age 3, numerous minor motor seizures characterized by head nodding were noted daily and clonazepam was added to his drug regimen. A repeated EEG revealed frequent paroxysms of atypical spike-wave activity. Ethosuximide was substituted for clonazepam at a dose of 250 mg twice a day. One hour after the second dose, which was 12 hours after the first dose, involuntary movements developed. The child moved about the room purposelessly unless re¬ strained by his parents; chorea was present in the extremities, and was associated with facial grimacing, lip smacking, and tongue protrusion. He was alert and no seizures were noted. An intravenous injection of diazepam put the child to sleep for three hours. On rising the movements returned, though with less severity, and continued to diminish during the next day. Ethosux¬ imide had been discontinued after the second dose and the symptoms disappeared within 36 hours of their onset. Case 2.—This 8-year-old boy was re¬ ferred at age 4 for the evaluation of delayed development. A diagnosis of unspecified psychomotor retardation was made. Minor motor seizures were noted a year later and an EEG demonstrated paroxysmal polyspike discharges of centrencephalic origin. At first, the seizures were well controlled with phenytoin and clonazepam, but later recurred and pro¬ gressively increased in frequency. Ethosuximide, 100 mg twice a day, was added. Approximately 12 hours after the first dose, the child became restless and developed uncontrollable movements of the limbs and face. Facial grimacing and
tongue protrusion as
sufficiently severe feeding. Despite these
were
to interfere with
symptoms, the parents continued
to ad¬ minister the ethosuximide and on the tenth day increased the dose to 250 mg as origi¬ nally instructed. Two weeks later, they first telephoned in to report the involun¬ tary movements as well as a marked improvement in seizure control. They were instructed to discontinue ethosuximide
immediately.
The child was examined 24 hours after his last dose and the movements were reported to have diminished. The child was restless unless restrained. Buccolingual
Downloaded From: http://archpedi.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/31/2015
Attack Rate of Pneumocystis carinii Pneumonitis (PCP) in Children Receiving Treatment for Acute Lymphatic Leukemia
Treatment No TMP-SMZ High-dose brief TMP-SMZ* Placebo (Hughes et
Patients With PCP
al'0)
Low-dose contin¬ uous TMP-SMZ (Hughes et al'°)t
'Compared =
2
no
4.15,
with =
0.02.
was
the basis for
17
80
0
80
pattern since
their infections occurred randomly
throughout the entire period of treat¬
ment. This difference may be related to the intensity of therapy at differ¬ ent phases of the disease. Both
Hughes' and our group have noted the correlation of increased PCP with the addition of more intense chemothera¬ py/'2
TMP-SMZ, x2
=
Since the incidence of PCP in
.357,
high-dose
TMP-SMZ,
Disease Control noted an association between the length of hospitalization and development of pneumocystis pneumonia. In addition, a greater percentage of hematology staff, com¬ pared with other hospital staff, were seropositive for pneumocystis anti¬ bodies. Both observations suggest hos¬ pital transmission of the organism/ Recent animal studies confirm the spread of pneumocystis organisms by horizontal transmission." The results by Hughes et al·" employing a lower dose of TMP-SMZ (TMP 4 mg and SMZ 20 mg/kg/day) during the entire period of chemo¬ are
group
not conform to this
Patients Without PCP 13
Failure of patient compliance is unlikely because all oral medications were given with nursing supervision in the clinic or parent care facility. During our institutional outbreak of PCP, investigation by the Center for
therapy
our
initiating the prophylaxis program at four weeks. Hughes's patients did
0.28.
tCompared =
with
4
in
clearly superior
to
our
results. Comparison of results be¬ tween the placebo and treated group in Hughes's series and between the no TMP-SMZ group and treated group in our series shows the superiority of long-term low-dose TMP-SMZ (Ta¬ ble). The attack rate of the groups who did not receive effective prophylaxis are quite similar: 17 of 80 (21%) of Hughes's placebo group compared with four of 17 (23%) of our nontreated group but, the time of onset of PCP differed. Our patients conform more to the general experi¬ ence of the investigators of the Chil¬ dren's Cancer Study Group \vho noted that the greatest frequency of pulmo¬ nary infections in 569 patients with ALL occurred within the first 100
8. Ruebush TK, Weinstein RA, Baehner RL, et al: An outbreak of pneumocystis pneumonia in children with acute leukemia. Am J Dis Child, to be published. 9. Walzer PD, Schnelle V, Armstrong D, et al: Experimental transmission studies of Pneumocystis carinii in nude mice. Science 197:177-179, 1977. 10. Hughes W, Kuhn S, Chaudhary S, et al: Successful chemoprophylaxis for Pneumocystis carinii pneumonitis. Pediatr Res 11:501, 1977. 11. Siegel SE, Baehner RL, Nesbitt M: Pulmonary disease during the therapy of childhood acute lymphocytic leukemia. Abstracts American Society of Hematology, 1974. 12. Hughes WT, Feldman S, Aur RJ, et al: Intensity of immunosuppressive therapy and the incidence of Pneumocystis carinii pneumonitis. Cancer 36:2004-2009, 1975.
our
patients who received TMP-SMZ was not decreased, but simply delayed in onset for a period up to 170 days after initiation of chemotherapy and the rate of PCP in our non-ALL patients increased to 17%, we have abandoned the short-term high-dose TMP-SMZ as prophylaxis and are now evaluating the efficacy of low dose continuous TMP-SMZ for all our patients at LAWRENCE J. WOLFF, MD ROBERT L. BAEHNER, MD Department of Pediatrics Indiana University School of Medicine James Whitcomb Riley Hospital for Children Indianapolis, IN 46202 This investigation was supported by grant IN\x=req-\ 450 awarded by the American Cancer Society and by a grant from the James Whitcomb Riley Memorial Association. 1. Stevens DA: Current concepts in cancer: II. Infections in cancer patients. Int J Radiat Oncol Biol Phys 1:295-296, 1976. 2. Simone JV, Holland E, Johnson W: Fatalities during remission of childhood leukemia. Blood 39:759-770, 1972. 3. Hughes WT, Feldman S, Sanyal SK: Treatment of Pneumocystis carinii pneumonitis with trimethoprim-sulfamethoxazole. Can Med Assoc J 112:47S-50S, 1975. 4. Hughes WT, Feldman S, Chaudhary S, et al: Comparison of trimethoprim-sulfamethoxazole and pentamidine in the treatment of Pneumocystis carinii pneumonitis. Pediatr Res 10:399, 1976. 5. Lau WK, Young LS: Trimethoprim-sulfamethoxazole treatment of Pneumocystis carinii pneumonia in adults. N Engl J Med 295:716-718, 1976. 6. Wolff LJ, Bartlett MS, Baehner RL, et al: The causes of interstitial pneumonitis in immunocompromised children: An aggressive systematic approach to diagnosis. Pediatrics 60:41-45, 1977. 7. Hughes WT, McNabb PC, Makres TD, et al: Efficacy of trimethoprim and sulfamethoxazole in the prevention and treatment of Pneumocystis carinii pneumonitis. Antimicrob Agents Chemother 5:289-293, 1974.
Association of Prune Belly Syndrome and Gastroschisis
Prune belly and gastroschisis are syndromes that have been well described in the literature. Prune belly or the "triad syndrome" is composed of cryptorchidism, deficiency of the abdominal wall, musculature, and urinary tract abnormalities.1
-4 Gastroschisis is a congenital full-thickness cleft in the abdominal wall, usually to the right of a normally inserting umbilical cord, and evisceration through the defect with no overlying membrane.5 -8 There have been more than 200 cases of prune belly and greater than 120 cases of gastroschisis reported in the literature, but the two syndromes have not, to our knowledge, been described together in the same patient. This report describes a patient with both prune belly syndrome and gastroschisis.
Report of a Case.\p=m-\Thisinfant was deliva gravida 9, para 7, 37-year-old woman on June 23, 1976 in Chicago Osteopathic Hospital. Excessive maternal alcohol consumption was the only complication of pregnancy. A previous child with spina bifida and hydrocephalus had died at the age of 2 years. Labor began at 36 weeks by dates and lasted two hours with membrane rupture occurring one hour prior to deliv¬ ery. No systemic or local anesthetics were administered and the delivery was sponta¬ neous vaginal. Apgar scores were 3 and 4 at one and five minutes respectively, and the patient required resuscitation for 15 min¬ utes. A large defect in the abdominal wall with evisceration was noted in the delivery room. The patient was transferred to the Wyler Children's Hospital Intensive Care Nursery. On examination, the patient was in no distress and weighed 2,165 gm. The Dubo¬ witz score indicated a gestational age of 37 ered from
weeks. There was a 6-cm defect in the abdominal wall to the right of a normal
Downloaded From: http://archpedi.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/31/2015
umbilical cord through which the stomach, the entire small intestine, and two-thirds of the colon protruded. There was a midgut malrotation. Only minimal thickening of the bowel wall was present. The abdominal wall musculature, on examination and
subsequently The scrotal
at surgery,
was
hypoplastic.
sac was small and the testes not palpable. There were supernu¬ merary digits on each hand and anonychia
were
of the pollicis and hallucis bilaterally. The remainder of the physical examination was unremarkable. At 2 hours of age the first stage of a twostage closure was performed employing a silastic pouch to cover the defect according to the method devised by Schuster." Ladd's bands were dissected and gastrostomy was performed. Postoperatively the patient's condition was managed with a pressure ventilator, antibiotics, and peripheral par¬ enteral nutrition. Complications included a urinary fistula probably involving the urachus, a wound cellulitis with subsequent fecal fistula, and two urinary tract infec¬ tions. The cystogram showed a small, irregular bladder with reflux into markedly dilated ureters and calyceal systems bilaterally. There was evidence of bilateral loss of renal cortex. The urethra appeared normal on the voiding films. There was no evidence of posterior urethral valves. The intravenous pyelogram demonstrated a dilated pelvocalyceal system on both sides. At 11 weeks of age the patient was discharged from the hospital weighing 2,175 gm and taking feedings by mouth ad lib. He had normal stools and spontaneous sterile urine production. The BUN and creatinine levels were 6.0 mg/100 ml and 0.3 mg/100 ml, respectively. Chromosome studies were normal. At 7 months of age, when most recently seen, clinically his urinary and bowel func¬ tion continued to be normal.
Comment.—Gastroschisis is theo¬ rized to result from a failure of local¬ ized differentiation and subsequent résorption of embryonic mesenchyme in one of the two lateral folds of mesenchyme in the abdominal wall. Subsequently, the ectoderm also invo¬ lutes, leaving a full-thickness abdom¬ inal wall cleft. The defect is unilateral and originates during the latter part of the third week of embryonic life.5 Ives' has proposed that the prune belly syndrome is caused by a localized abnormality of the mesoderm during the time of the initial formation of the primitive streak and its outflow of mesoderm early in the third week of development. A defect in the paraxial mesoderm would account for the abdominal wall deficiency. The inter¬ mediate mesoderm deficiency would explain the renal abnormalities in the
musculature of the ureters, bladder and gubernaculum, accounting for megalometers, megacystis and failure of descent of the testes respectively. This case report describing a pa¬ tient with both gastrochisis and prune belly supports Ives' hypothesis. One case report exists of a patient with both prune belly and omphalocele.4 Omphalocele is also thought to be the result of a defect during the last part of the third embyronic week, provid¬ ing supporting evidence for the hypo¬ thesis.
CRAIG WILLERT, MD HOWARD COHEN, MD
YA-MEI T. Yu, MD JOHN D. MADDEN, MD Pritzker School of Medicine of The University of Chicago Department of Pediatrics 950 E 59th St
Chicago,
IL 60637
1. Eagle JF, Barrett GS: Congenital deficiency of abdominal musculature with associated genito-urinary abnormalities: A syndrome, report of nine cases. Pediatrics 6:721-736, 1950. 2. Rogers LW, Ostrow PT: The prune belly syndrome: Report of 20 cases and description of a lethal variant. J Pediatr 83:786-793, 1973. 3. Ives EJ: The abdominal muscle deficiency triad syndrome\p=m-\Experiencewith ten cases. Birth Defects: Original Article Series, No. 4, vol 10, pp 127-135, 1974. 4. Cremin BJ: The urinary tract anomalies associated with agenesis of the abdominal walls. Br J Radiol 44:767-772, 1971. 5. Lewis JE, Kraeger RR, Danis RK: Gastroschisis. Arch Surg 107:218-222, 1973. 6. Gilbert MG, Mencia LF, Puranik SR, et al: Management of gastroschisis and short bowel: Report of 17 cases. J Pediatr Surg 7:598-607, 1972. 7. Mahour GH, Weitzman JJ, Rosenkrantz JG: Omphalocele and gastroschisis. Ann Surg 177:478-482, 1973. 8. Moore TC: Gastroschisis with antenatal evisceration of intestines and urinary bladder. Ann Surg 158:263-269, 1963. 9. Schuster SR: A new method for the staged repair of omphalocele. Surg Gynecol Obstet 125:837, 1967.
Dyskinesia and Akathisia Induced by Ethosuximide Ethosuximide (Zarotin)
was introduced in 1958 for the treatment of petit mal epilepsy' and has since been found useful in the control of minor motor seizures. We report the case histories of two children in whom a syndrome characterized by motor restlessness (akathisia) and purposeless movements of the tongue, jaw, face, and extremities (dyskinesia) developed 12 hours after the first ingestion of ethosuximide. Among the various side effects attributed to this drug, this reaction must be exceed-
ingly rare as we have been able to find only one previous report.2 Report of Cases.\p=m-\Case1.\p=m-\Thepatient developing normally and was in good
was
health, when at the age of 8 months, a prolonged generalized seizure occurred in association with
a
fever of 38 C. Phenobar-
bital, diazepam, and paraldehyde were given. His physical examination was normal afterwards, as were blood chemistries, spinal fluid, and roentgenogram of
the skull. An EEG revealed suppression of the background activity in the right hemisphere. Despite the use of phénobarbital he had ten more seizures during the next six months. Phenytoin was tried but not found useful. At age 3, numerous minor motor seizures characterized by head nodding were noted daily and clonazepam was added to his drug regimen. A repeated EEG revealed frequent paroxysms of atypical spike-wave activity. Ethosuximide was substituted for clonazepam at a dose of 250 mg twice a day. One hour after the second dose, which was 12 hours after the first dose, involuntary movements developed. The child moved about the room purposelessly unless re¬ strained by his parents; chorea was present in the extremities, and was associated with facial grimacing, lip smacking, and tongue protrusion. He was alert and no seizures were noted. An intravenous injection of diazepam put the child to sleep for three hours. On rising the movements returned, though with less severity, and continued to diminish during the next day. Ethosux¬ imide had been discontinued after the second dose and the symptoms disappeared within 36 hours of their onset. Case 2.—This 8-year-old boy was re¬ ferred at age 4 for the evaluation of delayed development. A diagnosis of unspecified psychomotor retardation was made. Minor motor seizures were noted a year later and an EEG demonstrated paroxysmal polyspike discharges of centrencephalic origin. At first, the seizures were well controlled with phenytoin and clonazepam, but later recurred and pro¬ gressively increased in frequency. Ethosuximide, 100 mg twice a day, was added. Approximately 12 hours after the first dose, the child became restless and developed uncontrollable movements of the limbs and face. Facial grimacing and
tongue protrusion as
sufficiently severe feeding. Despite these
were
to interfere with
symptoms, the parents continued
to ad¬ minister the ethosuximide and on the tenth day increased the dose to 250 mg as origi¬ nally instructed. Two weeks later, they first telephoned in to report the involun¬ tary movements as well as a marked improvement in seizure control. They were instructed to discontinue ethosuximide
immediately.
The child was examined 24 hours after his last dose and the movements were reported to have diminished. The child was restless unless restrained. Buccolingual
Downloaded From: http://archpedi.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/31/2015
