Twenty-four-hour ambulatory EEG monitoring in infantile spasms

Twenty-four-hour ambulatory EEG (AEEG) recordings were performed in 74 infants with West Syndrome (WS) who had not received corticosteroids before the recording. EEG analysis was performed visually for interictal background activity as well as for ictal events: spasms (isolated or in clusters) and other seizures either generalized or partial. Six hundred fifty-four seizures were recorded in 67 patients. Partial seizures (PS) were noted in 31 infants (51% of symptomatic WS cases, 33% of cryptogenic WS cases). In 14 patients, PS were immediately followed by a cluster of spasms consisting of a single ictal event. Patients with PS had an asymmetrical interictal background activity in 85% of cases, with no return to hypsarrhythmia between spasms in a given cluster. AEEG is a reliable method to detect and analyze ictal events in infants with WS. In this population, patients with unfavorable outcome of both epilepsy and psychomotor development have PS. Therefore, the existence of PS may contribute to etiologic diagnosis and prognostic evaluation.     

Randomized multicenter trial comparing synchronized and conventional intermittent mandatory ventilation in neonates

OBJECTIVE: To compare synchronized intermittent mandatory ventilation (SIMV) and conventional intermittent mandatory ventilation (IMV) in neonates. STUDY DESIGN: Prospective, multicenter, randomized clinical trial. SETTING: Level III neonatal intensive care units at six university or children's hospitals. PATIENTS: Three hundred twenty-seven infants receiving conventional IMV for respiratory distress syndrome, pneumonia, or meconium aspiration pneumonitis were randomly assigned a 7.5 +/- 6 hours of age to either continue with IMV or change to SIMV. Infants assigned to each mode of ventilation had similar birth weight (BW), gestational age, and Apgar scores at birth, and similar oxygenation indexes at randomization. They received similar surfactant therapy and had similar incidence of sepsis, seizures, secondary pneumonia, and necrotizing enterocolitis. In the infants with BW less than 1000 gm, more infants receiving IMV had surgical ligation of their patent ductus arteriosus than did those receiving SIMV (27 vs. 7 %; p = 0.02). ANALYSIS: Data was analyzed overall for all infants and also separately within three BW groups: less than 1000 gm, 1000 to 2000 gm, and more than 2000 gm. The 1000 to 2000 gm BW group was further analyzed in subgroups weighing 1000 to 1499 gm and 1500 to 2000 gm. RESULTS: In all infants, at 1 hour after randomization, the infants receiving SIMV had a lower mean airway pressure than those receiving IMV (8.08 +/- 2.15 vs. 8.63 +/- 2.59; p<0.05), with similar fractions of inspired oxygen and oxygenation indexes. Infants whose BW was 1000 to 2000 gm at 0.5 hour required a lower fraction of inspired oxygen with SIMV than with IMV (0.52 +/- 0.20 vs. 0.62 +/- 0.27; p<0.05) and had better oxygenation at 1 hour, as shown by lower oxygenation indexes with SIMV than with IMV (6.14 +/- 4.17 vs. 9.42 +/- 8.41; p = 0.01). Infants whose BW was 1000 to 2000 gm received a lower number of unit doses of sedative/analgesic drugs per infant during the first 4 days of SIMV than did infants receiving IMV (3.8 +/- 3.4 vs 6.3 +/- 5.5 unit doses; p = 0.02). Infants whose BW was more than 2000 gm had a shorter duration of mechanical ventilation with SIMV than with IMV (median, 72 vs 93 hours; p = 0.02). Three of the forty-six infants receiving IMV but none of the 47 infants receiving SIMV required extracorporeal membrane oxygenation. In the infants with BW less than 1000 gm, fewer infants treated with SIMV required supplemental oxygen at 36 weeks of postconceptional age than did those treated with IMV (47 vs 72%; p<0.05). In 83 infants whose lungs were mechanically ventilated for 14 days or longer, all with BW less than 2000 gm, those treated with SIMV regained their BW earlier than those treated with IMV (median, 21.5 vs 29 days; p<0.01). There were no differences in the rates of death, intraventricular hemorrhage (grades III and IV), air leak, need for pharmacologic paralysis, or need for supplemental oxygen at 28 days. CONCLUSIONS: We found that SIMV was at least as efficacious as conventional IMV, and may have improved certain outcomes in BW-specific groups.     

Retinal lesions in tuberous sclerosis

Retinal lesions in 116 patients with tuberous sclerosis included three types: the relatively flat, semitransparent, non-calcified tumors; the more commonly described nodular, calcified tumors; and a third lesion that possessed features of the other two. Other less definite pigmented and plaque-like lesions also were seen. The evolution of a relatively flat, noncalcified lesion into an elevated nodular, apparently calcified lesion during an interval of two decades was photographically recorded.     

Randomized controlled trial comparing same-day discharge with hospital stay following haemorrhoidectomy

Neurological complications of 5-fluorouracil (5-FU) chemotherapy are uncommon events. The two patients presented demonstrate two manifestations of 5-FU neurotoxicity, namely a cerebellar syndrome in association with global motor weakness and bulbar palsy, and a bilateral third cranial (oculomotor) nerve palsy. Both highlight the rapid onset and severity of these unusual side effects but also emphasize that, unlike paraneoplastic syndromes or central nervous system involvement by tumour, complete spontaneous recovery is a potential outcome.     

Massive renal angiomyolipoma in tuberous sclerosis

Endoscopic surgery has been used as a new procedure to simplify different surgical processes. The goal of this study was to evaluate the benefits of endoscopic retroperitoneal surgery for lumbar sympathectomies. Between February 93 and November 95 we performed 35 lumbar sympathectomies using this technique. All patients were arteritic. The results were as follows: for 25% of the patients, conversion classical open technique was required; 6% complications (septic); 3% of the patients died. In comparing the various techniques of sympathectomy and sympatholysis, it would appear that the endoscopic technique produces fewer complications. However we believe that a learning period is necessary before this technique can be fully mastered.     

Hemimegalencephaly and focal megalencephaly in tuberous sclerosis complex

We describe two children with complex cortical malformations as well as the typical intracranial manifestations of tuberous sclerosis complex. One child had hemimegalencephaly and the other had extensive focal megalencephaly. These cases are discussed in terms of the current concepts of cortical malformations.     

Therapeutic efficacy of ACTH in symptomatic infantile spasms with hypsarrhythmia

The records of twenty-six infants with both symptomatic infantile spasms and classic hypsarrhythmia were reviewed to determine the efficacy of various ACTH dosages and time of initiation of therapy. Mean age of infantile spasm onset was 6.4 months. Most patients (13) had sustained perinatal hypoxic-ischemic insults. Seventeen patients (65%) had complete cessation of spasms. Between these responders and the 9 nonresponders there was no difference in duration of spasms prior to treatment (2.6 and 2.0 months) or mean ACTH dose (87.4 and 84.5 U/m2, respectively). Infants treated with high-dose ACTH (> 100 U/m2) did not have an improved response rate. The most favorable outcomes were associated with spasm onset at > 8 months of age (all of whom were responders, regardless of dose) or when treatment was started within 1 month of onset of infantile spasms with > 80 U/m2 ACTH (88% responders). Infants treated more than 2 months after onset often did not respond (57%) regardless of dose. Nonresponders with spasm onset at < 4 months of age had the worst prognoses; all had poorly controlled seizures and regressed developmentally. Although all infants in the study were neurologically abnormal, development either improved or did not deteriorate in most responder infants following spasm resolution and one-half remained seizure free. Nonresponder infants continued to have infantile spasms or other seizure types. These data suggest that ACTH is valuable in the treatment of significantly impaired infants with symptomatic infantile spasms, but the most important determinants of outcome may be age of onset and rapidity of treatment rather than dosage.     

Diagnosis and management of tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous disorder with a high spontaneous mutation rate. Understanding of this disorder has greatly increased in recent years. Two chromosomal loci can produce the TSC phenotype: 9q34 and 16p13. These appear to code for proteins that have a tumor suppressor function. TSC results in hamartomas that affect various organ systems, most commonly brain, skin, heart, and kidney. Previously thought to consist of intractable seizures, facial angiofibromas, and dementia, increasing numbers of persons with less severe involvement have been identified. Diagnostic criteria, various types of lesions, and medical management are reviewed.     

Loss of heterozygosity in tuberous sclerosis hamartomas

We have previously described in tuberous sclerosis (TSC) hamartomas the phenomenon of loss of heterozygosity (LOH) for DNA markers in the region of both the TSC2 gene on chromosome 16p13.3 and the TSC1 gene on 9q34. We now describe the spectrum of LOH in 51 TSC hamartomas from 34 cases of TSC. DNA was extracted from leucocytes or normal paraffin embedded tissue, and from frozen paraffin embedded hamartoma tissue from the same patient. The samples were analysed for 11 markers spanning the TSC1 locus and nine markers spanning the TSC2 locus. Twenty-one of 51 hamartomas showed LOH (41%). There was significantly more LOH on 16p13.3, with 16 hamartomas showing LOH around TSC2, and five in the vicinity of TSC1. No hamartoma showed LOH for markers around both loci. All the areas of LOH on chromosome 9 were large, but the smallest region of overlap lay between the markers D9S149 and D9S114, providing independent evidence for the localisation of the TSC1 gene. These data show that LOH is a common finding in a wide range of hamartomas, affecting the same TSC locus in different lesions from the same patient but not affecting both loci. These data support the hypothesis that both the TSC genes act as tumour suppressors and that the manifestations of TSC in patients with germline TSC mutations rise from "second hit" somatic mutations inactivating the remaining normal copy of the TSC gene.     

Randomized trial comparing three forms of pelvic floor repair for neuropathic faecal incontinence

A randomized controlled trial in women with neuropathic faecal incontinence compared total pelvic floor repair (n = 12) with anterior levatorplasty and sphincter plication alone (n = 12) and postanal repair alone (n = 12). Review at 6 and 24 months indicated that results were significantly better for total pelvic floor repair than either of the other procedures. Complete continence was achieved in eight of the 12 patients 2 years after total pelvic floor repair. Only total repair significantly elongated the anal canal. Both total pelvic floor repair and anterior levatorplasty improved sensation in the upper anal canal.     

Temporal relationship modeling: DTP or DT immunizations and infantile spasms

The time relationship between DTP immunization and infantile spasms (IS) onset was examined using three models--association, temporal shift, and no-effect--and the case/control data from the National Childhood Encephalopathy Study (NCES). Infantile spasms cases classified as being previously abnormal (e.g., tuberous sclerosis complex patients) showed a no-effect relationship, whereas those classified as previously normal suggested a fit to the temporal shift model, i.e. no increase in number of cases but a shortening of time to onset of seizure. No data fit the association model. Analyses for vaccine complications should examine for temporal changes (i.e. temporal shift) in addition to increased risks.     

Evolution of cardiac rhabdomyoma in tuberous sclerosis complex

The objective of the study was to define the longitudinal evolution of cardiac rhabdomyomas (CR) in patients with tuberous sclerosis complex (TSC). A cohort of patients with TSC who had undergone videotaped echocardiographic (ECHO) examination during the 10-year interval (1984-1994) were retrospectively studied by reviewing and quantifying the CR appearance and associated cardiac abnormalities in sequentially obtained ECHO examinations. Sixteen patients with TSC (8 males) underwent a total of 35 recorded studies. Ten of the 16 (62.5%) had CR identified at initial study; none were found in the atria. Localization was the ventricular walls as compared with the ventricular septum by a ratio of 2:1. The number of CRs sequentially studied declined as follows; initial study: 23 lesions in 10 patients; second study: 16 lesions in 8 patients; third study: 12 lesions in 5 patients; and fourth study: 4 lesions in 2 patients. Total CR size index declined at each study as follows: initial index of 2,684; second index of 1,746 (-35% from initial); third index 1,141 (-57% from initial); and fourth index 705 (-74% from initial). Complete spontaneous regression of CR was seen by age 6 years with prolonged gradual resolution thereafter. Two patients had bicuspid aortic valves and two had conduction defects. Patients with TSC who have CR can be expected to experience a decline in both the number and size of CR over time; early complete regression on ECHO occurs before age 6 years.