Richard Towbin

Mutism and pseudobulbar symptoms after resection of posterior fossa tumors in children: incidence and pathophysiology.

MUTISM AND A variety of other neurobehavioral symptoms have been reported anecdotally after the removal of posterior fossa mass lesions. To determine the incidence and clinical spectrum of this syndrome, a detailed review was performed of patients undergoing resection of infratentorial tumors at our institution during the last 9 years; 12 of 142 patients (8.5%) manifested this syndrome, the largest series of such patients reported to date. Each child had a lesion that involved the vermis; seven had medulloblastomas, three had astrocytomas, and two had ependymomas. The incidence among children with vermian neoplasms was 13%. Ten children underwent division of the inferior vermis during tumor resection, and three had a superior vermian incision; one child underwent both superior and inferior vermian incisions. In 10 children, mutism developed in a delayed fashion postoperatively. The speech disturbance was associated with poor oral intake in 9 children, urinary retention in 5, long-tract signs in 6, and bizarre personality changes, emotional lability, and/or decreased initiation of voluntary movements in all 12. Neuropsychiatric testing, performed in seven children, confirmed impairments not only in speech but also in initiation of other motor activities. Ten children regained normal speech, bladder control, and neurological functioning, other than ataxia and mild dysarthria, within 1 to 16 weeks; two children had significant residual deficits. Characteristically, affect and oral intake returned to their preoperative baseline before the speech difficulties began to resolve. A detailed radiological review of these cases in parallel with 24 cases of vermian tumors without mutism identified only one factor that was significantly associated with the mutism syndrome, bilateral edema within the brachium pontis (P < 0.01). Neither the size of the tumor nor the length of vermian incision was associated with the development of mutism. The clinical features of this syndrome in the context of these imaging findings suggest that the mutism syndrome results from transient impairment of the afferent and/or efferent pathways of the dendate nuclei that are involved in initiating complex volitional movements. The clinical courses of our patients are presented and compared with those of similar cases in the literature in an attempt to evaluate the validity of this hypothesis.

Mutism and Pseudobulbar Symptoms after Resection of Posterior Fossa Tumors in Children

MUTISM AND A variety of other neurobehavioral symptoms have been reported anecdotally after the removal of posterior fossa mass lesions. To determine the incidence and clinical spectrum of this syndrome, a detailed review was performed of patients undergoing resection of infratentorial tumors at our institution during the last 9 years ; 12 of 142 patients (8.5%) manifested this syndrome, the largest series of such patients reported to date. Each child had a lesion that involved the vermis ; seven had medulloblastomas, three had astrocytomas, and two had ependymomas. The incidence among children with vermian neoplasms was 13%. Ten children underwent division of the inferior vermis during tumor resection, and three had a superior vermian incision ; one child underwent both superior and inferior vermian incisions. In 10 children, mutism developed in a delayed fashion postoperatively. The speech disturbance was associated with poor oral intake in 9 children, urinary retention in 5, long-tract signs in 6, and bizarre personality changes, emotional lability, and/or decreased initiation of voluntary movements in all 12. Neuropsychiatric testing, performed in seven children, confirmed impairments not only in speech but also in initiation of other motor activities. Ten children regained normal speech, bladder control, and neurological functioning, other than ataxia and mild dysarthria, within 1 to 16 weeks ; two children had significant residual deficits. Characteristically, affect and oral intake returned to their preoperative baseline before the speech difficulties began to resolve. A detailed radiological review of these cases in parallel with 24 cases of vermian tumors without mutism identified only one factor that was significantly associated with the mutism syndrome, bilateral edema within the brachium pontis (P < 0.01). Neither the size of the tumor nor the length of vermian incision was associated with the development of mutism. The clinical features of this syndrome in the context of these imaging findings suggest that the mutism syndrome results from transient impairment of the afferent and/or efferent pathways of the dendate nuclei that are involved in initiating complex volitional movements. The clinical courses of our patients are presented and compared with those of similar cases in the literature in an attempt to evaluate the validity of this hypothesis.

Percutaneous gastrojejunostomy versus Nissen fundoplication for enteral feeding of the neurologically impaired child with gastroesophageal reflux

To determine the optimal method of providing enteral feeding to neurologically impaired children with gastroesophageal reflux, Nissen fundoplication with simultaneous gastrostomy tube placement (NGT) was compared with anterograde percutaneous gastrojejunostomy (APGJ), a nonsurgical procedure performed under fluoroscopic guidance. The records of 112 neurologically impaired children with gastroesophageal reflux were retrospectively reviewed; 68 had undergone NGT and 44 APGJ. Follow-up data were available for 45 NGT patients (mean age, 6.4 years) and 34 APGJ patients (mean age, 7.9 years). Mean follow-up was 1.8 years in the NGT group and 2.5 years in the APGJ group. Complications resulting from either procedure were classified either as major, which included treatment failures or morbidity resulting in prolonged hospitalization, or as minor, those requiring outpatient treatment only or not directly caused by the procedure. The NGT group had a significantly higher incidence of major complications in comparison with the APGJ group (33.3% vs 11.8%, p < 0.05). Ten patients (22.2%) in the NGT group required reoperation for complications; six required a second NGT for wrap hernia, failure, and continued gastroesophageal reflux. Two patients (5.9%) in the APGJ group required surgery for complications; one of these eventually required an NGT, and the other had an intussusception that necessitated a small-bowel resection. Minor complications were more common in the APGJ group than in the NGT group (44.1% vs 6.6%); the majority of complications were related to the jejunostomy tube. Premature replacement or reinsertion of the jejunostomy tube was necessary in 14 APGJ patients (32%). The mortality rate was 8.8% in the NGT group and 5.9% in the APGJ group (p = not significant). No death occurred within 30 days of either procedure. We conclude that APGJ is a safe alternative method for feeding the neurologically impaired child with gastroesophageal reflux.

Use of indium-111-labeled hepatocytes to determine the biodistribution of transplanted hepatocytes through portal vein infusion.

PURPOSE Hepatocyte transplantation is useful for ex vivo gene therapy and liver repopulation. Methods for hepatic reconstitution were recently developed, but hepatocyte transplantation systems must be optimized. The authors report their experience with In-111 oxyquinolone labeling of a test dose of hepatocytes (108 cells) for noninvasive assessment of the biodistribution of transplanted hepatocytes in a 5-year-old child with omithine transcarbamoylase deficiency. MATERIALS AND METHODS Donor hepatocytes (approximately 108) were radiolabeled using a commercially available In-111 oxyquinolone solution (specific activity of 1 mCi/ml). RESULTS The overall labeling efficiency was 36.4%. A final dose of approximately 290 ,uCi of the In-111-labeled hepatocytes in 10 ml serum-free phosphate-buffered saline was infused percutaneously into the portal vein approximately 2.5 hours after their preparation. The study was performed 3 hours before cell transplantation (109 cells). Quantitative analysis of the biodistribution of In-111-labeled hepatocytes indicated that cells were predominantly localized in the liver immediately after portal vein-infused transplantation. The predominant hepatic distribution was persistent for as long as 7 days after the procedure, with an average liver-to-spleen ratio of 9.5 to 1. No significant pulmonary radiotracer uptake was present. CONCLUSION These results indicate that In-111 labeling of hepatocytes is useful for the short-term noninvasive analysis of the biodistribution of transplanted hepatocytes.

Intrahepatic chemoembolization in unresectable pediatric liver malignancies.

Objective. To determine the effectiveness of a new miltidisciplinary approach using neoadjuvant intrahepatic chemoembolization (IHCE) and liver transplant (OLTx) in patients with unresectable hepatic tumors who have failed systemic chemotherapy.¶Materials and methods. From November 1989 to April 1998, 14 children (2–15 years old) were treated with 50 courses of intra-arterial chemotherapy. Baseline and post-treatment contrast-enhanced CT and alpha-fetoprotein levels were performed. Seven had hepatoblastoma, and 7 had hepatocellular carcinoma (1 fibrolamellar variant). All patients had subselective hepatic angiography and infusion of cisplatin and/or adriamycin (36 courses were followed by gelfoam embolization). The procedure was repeated every 3–4 weeks based on hepatic function and patency of the hepatic artery.¶Results. Six of 14 children received orthotopic liver transplants (31 courses of IHC). Pretransplant, 3 of 6 showed a significant decrease in alpha-fetoprotein, while only 1 demonstrated a significant further reduction in tumor size). Three of 6 patients are disease free at this time. Three of 6 patients died of metastatic tumor 6, 38, and 58 months, respectively post-transplant. One of 14 is currently undergoing treatment, has demonstrated a positive response, and is awaiting OLTx. Three of 14 withdrew from the program and died. Four of 14 patients developed an increase in tumor size, developed metastatic disease, and were not transplant candidates. Two hepatic arteries thrombosed, and one child had a small sealed-off gastric ulcer as complications of intrahepatic chemoembolization.¶Conclusion. The results of intrahepatic chemoembolization are promising and suggest that some children who do not respond to systemic therapy can be eventually cured by a combination of intrahepatic chemoembolization orthotopic liver transplant. Alpha-fetoprotein and cross-sectional imaging appear to be complementary in evaluating tumor response. IHCE does not appear to convert an anatomically unresectable lesion to a candidate for partial hepatectomy.

Outcome of Children With Cerebral Edema Caused by Fulminant Hepatic Failure

Mortality is high in patients with fulminant hepatic failure (FHF). Neurologic complications of encephalopathy and cerebral edema are major contributors to mortality. Orthotopic liver transplantation has improved survival in these patients. However, the complexity of medical and surgical problems in this patient population, coupled with a severe shortage of organs, requires careful patient selection. The aim of this study was to describe the neurologic outcome of children with FHF who developed radiologically apparent cerebral edema. The hospital and outpatient records and radiologic studies of 20 children with FHF admitted to Childrens Hospital of Pittsburgh from 1981-1995 who developed encephalopathy and computed tomographic evidence of cerebral edema were reviewed. Fourteen patients died (70%), three were left with severe neurologic deficits (15%), and three were left with moderate deficits (15%). Survival was correlated with a lesser degree of coma. Histopathologic examination of eight brains demonstrated cerebral edema and widespread ischemic neuronal necrosis in all eight. The presence of radiographic cerebral edema in children with FHF is an objective measure that indicates a very poor prognosis. Termination of care is a reasonable option. Comprehensive monitoring of cerebral function and intracranial pressure is required in children with FHF. Orthotopic liver transplantation should be performed in children with severe and worsening encephalopathy before the development of radiographically apparent cerebral edema.

Evaluation and management of bilateral renal artery stenosis in children: A case series and review

This report describes the clinical course, diagnostic evaluation and management of six children with bilateral renal artery stenosis (RAS) and concurrent narrowing of the abdominal aorta. Except for one child with active arteritis, the others were asymptomatic. There were no clinical or laboratory features suggesting the etiology of hypertension in four of six patients, and diagnostic procedures, including Doppler duplex ultrasound and captopril scintigraphy, were unreliable in screening for such hypertension. Abdominal aortography and selective renal angiography confirmed the diagnosis of bilateral RAS and associated anatomical alterations of the aorta and its branches. The hypertension was severe and minimally responsive to antihypertensive agents. It was cured or improved after percutaneous transluminal angioplasty (PTA) of three vessels in two children with mid-vessel stenoses, while hypertension persisted after PTA of two mid-vessel stenoses in a third child and one vessel with ostium stenosis in a fourth child. Autotransplantation of seven kidneys in four children resulted in cure or significant improvement of the hypertension. Renal function was preserved in all children during a mean follow-up time of 41 months. Based on illustrative data from these six children, as well as information from a review of the literature, this report discusses the key diagnostic issues and stresses the potential advantages of renal autotransplantation in selected children with this disorder.

Management of hepatic venous obstruction after split-liver transplantation.

Abstract: Stenosis of the hepatic vein anastomosis is an unusual but critical complication after liver transplantation. In pediatric liver transplantation, the scarcity of size‐matched donors has required the use of segmental liver allografts, either as reduced‐size or split‐liver grafts. This report illustrates the primary use of a hepatic vein stent to manage hepatic venous outflow obstruction in a pediatric split‐liver recipient, and reviews experience in the management of hepatic venous outflow obstruction after liver transplant using stent methods.

Long-Term Outcome after Sagittal Synostosis Operations

We evaluated 27 children who had been operated on 5-10 years previously for sagittal synostosis. The mean age at operation was 0.55 years. Twenty-two children were treated by the senior authors technique, 4 by the Pi craniectomy technique and 1 by parasagittal sagittal strip craniectomies. The mean age at follow-up was 9.6 years. The cosmetic appearance of the head was graded independently by 3 examiners. Skull radiographs were graded by 2 examiners according to the appearance and presence of beaten copper markings. The cephalic index was measured. Frequent headaches were reported in 7 of 27 children and were migrainous in 3 of the 7. No child had papilledema. The childrens appearance was considered to be normal or mildly abnormally by the parents in every case and by the medical observers in 25 of 27 (93%). The only 2 children with an unacceptable appearance were either operated late (3.3 years) or had a craniofacial syndrome. Skull radiographs revealed a normal or mildly abnormal appearance in 18-19 children, depending on the observer. Beaten copper markings were observed to some extent in 14 of 27 cases and did not correlate with the presence of headaches. The cranial index ranged from 62 to 78 with a mean of 70 (normal 81). Sagittal reconstructions resulted in an acceptable appearance 5-10 years postoperatively in all cases operated on at less than 1 year of age who had no syndrome. The need for long-term follow-up of children after sagittal synostosis operations cannot be determined from this sample size.

Treatment of pentobarbitol sodium (Nembutal) hyperactivity: a new approach

Sir, Proper sedation of the pediatric patient is essential for obtaining high-quality imaging examinations and performing interventional procedures. This sedation is usually achieved using pentobarbital sodium alone or in combination. In approximately 1% of cases, pentobarbital sodium (Nembutal) causes paradoxical hyperactivity [1±3]. This reaction is similar to the hyperactivity seen in children with attention deficit hyperactivity disorder (ADHD), leaving the patient agitated and restless. Stimulants have been used to treat ADHD since 1937 [4]. While most treatments have centered on amphetamines, caffeine has also been successfully used to treat ADHD. As a result of this experience, it appeared that the paradoxical reaction secondary to pentobarbital could be treated in a similar fashion. We have found that caffeine administered orally in Mountain Dew (a soft drink) can be effective. In the past 2 years we have treated 25 children ranging in age from 14 months to 11 years for 26 episodes of paradoxical hyperactivity after injection of pentobarbital (mean dose 4.36 mg/kg). Of the 25 children treated, 24 calmed down within 10±90 min of ingestion. Each child received 1±12 oz (mean 3.5 oz) of Mountain Dew (mean 8.6 mg/kg caffeine). Barbituates affect the reticular activating system. Slovis and colleagues suggest that paradoxical hyperactivity does not occur with Versed or fentanyl administration [3]. While the mechanism of action of stimulants remains unknown, evidence suggests their effects on hyperactivity are produced by a combined effect on dopamine and nonadrenergic-dependant pathways in the CNS [5]. The currently accepted mechanism of action of caffeine is a blockade of methyl-xanthine sensitive adenosine receptors [6]. Adenosine promotes the onset of slow-wave sleep, reduced vigilance, effects opposite those of caffeine. Mountain Dew is readily available and is an excellent source of caffeine, 4.6 mg/oz. Patients readily drink this preparation. Children who develop paradoxical hyperactivity may be offered a can (12 oz). If necessary, the liquid may be given by NG tube. Alternatively, although not in our subgroup, caffeine may be given intravenously or orally (20 mg/kg). Our experience suggests that paradoxical hyperactivity can be treated with orally administered Mountain Dew (or other high-caffeine sodas). References