Increased QT dispersion in breath-holding spells.

UNLABELLED: Breath-holding spells (BHS) in children can be a frightening and clinically challenging paroxysmal, non-epileptic childhood disorder. The pathophysiology has been found to incorporate central nervous system dysregulation in addition to an underlying genetic predisposition. Akalin and colleagues found group differences (BHS versus controls) in QT dispersion and QTc dispersion. These differences, however, may have been affected mainly by normal sinus arrhythmia from the predominant cyanotic BHS cohort. CONCLUSION: The subtle differences measured in the current study between pallid and cyanotic breath-holder groups, in terms of increased QTc dispersion in the pallid group, may represent an additional factor impacted upon by the resting state of underlying central autonomic dysregulation.

Prospective study of children with cyanotic and pallid breath-holding spells.

OBJECTIVE: In this investigation, we sought to prospectively document the natural history of severe breath-holding spells (BHS) among children with both cyanotic and pallid BHS who were referred for neurologic consultation. DESIGN: Prospective cohort study. METHODS: A structured interview was undertaken at the time of initial consultation and at subsequent 1-year intervals regarding type of BHS, frequency of spells, associated phenomenon, sequelae, family history, and age at termination of spells. RESULTS: A total of 95 children (48 boys, 47 girls) with BHS were identified and followed over a 9-year interval. There were no significant differences between genders. Median onset age was between 6 and 12 months old with 15% presenting younger than 6 months. A median frequency of spells was weekly with 30% experiencing 1 or more spells per day. The median age at peak frequency was between 12 and 18 months old with a range extending from 6 months to 4 years of age. Of the patients whose BHS had remitted for >12 months' time (n = 67), the last spell occurred at a median age of 37 to 42 months. Of those children whose BHS were still occurring, the oldest age at time of latest spell was at 7 years old. Hypoxic convulsions were associated with BHS in

Assessment of stress in mothers of children with severe breath-holding spells.

BACKGROUND: Severe breath-holding spells (BHS) in children consist of a stereotypical sequence of provocation to cry, noiseless expiration, color change, and loss of consciousness. Parenting a child who exhibits BHS is likely more stressful than parenting a healthy child, owing to this additional medical concern. It is also likely more stressful than parenting a child with a convulsive seizure disorder (SD), because it is often not recognized or misdiagnosed as behavioral rather than medical. Mothers of children with BHS were hypothesized to suffer significantly greater stress than mothers of children with SD or mothers of children without any significant medical conditions. OBJECTIVES: To examine maternal stress in parenting a child who exhibits BHS, and to identify the specific areas of stress impact, compared with mothers of children with a convulsive SD and mothers of control children. METHODS: The Parenting Stress Index and questions regarding how mothers coped were individually administered to 34 mothers of children with BHS, 16 mothers of children with SD, and 16 mothers of children with no medical conditions (controls). RESULTS: Mothers of children with BHS or SD experience more overall stress and disruption in their attachment or understanding of their child, compared with control mothers. These groups of mothers (BHS and SD) also perceived their child as more distractible/hyperactive, less adaptive, and more demanding than did control mothers. However, mothers of the BHS group alone showed significant disruption in their sense of competence as a parent, maintaining self-identity, and receiving positive reinforcement from their child. Mothers of children with SD showed a similar trend, but it was not significant. These findings were not related to maternal health or feelings of depression/isolation, insufficient spousal support, child's mood, or other life stresses. CONCLUSION: Parenting a child with BHS or SD impacts a greater degree of life stress on mothers of these children than does parenting control children, although the stress is greater for the BHS group than for the SD group.

Headaches in patients with neurofibromatosis-1.

An analysis of patients followed with a diagnosis of neurofibromatosis-1 and headache was conducted. Characterization of headache type was done after chart review of 81 patients with neurofibromatosis-1 and headache. Consent was obtained for subsequent telephone interviews using a standardized questionnaire concerning the onset, characteristics, timing, triggers, and associated symptoms of the patients' headaches. Data was summarized and tabulated. Of 132 patients with neurofibromatosis-1, 81 were identified with any headache by screening history. Recurrent headaches were present in 77% of patients and in 47% of our neurofibromatosis-1 clinic population. Fifty-three of 81 patients were accessible for and agreeable to telephone interview. There were 23 male patients and 30 female patients aged 5 6/12 to 49 6/12 years, with a mean age of 20.9 years. Eighty-one percent reported having experienced recurrent headaches within the year. The majority reported onset of headache prior to the age of 10 years. Headache characteristics included the following: frequency of monthly or less, frontotemporal location, pulsating or pressing quality, and moderate severity (pain scale 4 to 5 out of 10). Headaches interfered with daily activities, had weekend occurrence, and had a duration less than 2 hours. Common headache triggers included stress, "change in weather," menstruation, fatigue, and certain foods. A high percentage of patients reported associated symptoms of nausea with or without vomiting (37%), phonophobia, photophobia, pallor, and visual scotoma. We classified 34% of the patients as having migraine (25% with aura, 9% without aura), 45% with nonmigrainous headache only, and 15% with mixed headache types (either intermittently), and 7.5% with other head pains. We conclude that patients with neurofibromatosis-1 are at greater risk for headaches than the general population. While the prevalence of both migraine and nonnigraine headache is somewhat greater than in the general population, the proportion of tension-type headache, especially in young children, is greater than expected.

Childhood head tremor.

We report here four children (three girls, one boy) with head tremor followed longitudinally, ages 15 months to 11 years, with follow-up over 1 to 8 years. Each demonstrated onset of head tremor between the ages of 5 and 10 months. In each case head tremor was characterized by a predominant "yes-yes" or "no-no" movement of the head. In two of the children the movement was slightly skewed with chin movement toward the shoulder. Oscillations were at a frequency of about 1 to 2 Hz. They were accentuated when sitting upright without head support, increased at times of movement, and dissipated while lying flat or sleeping. The children were unable to voluntarily suppress the action and did not experience any sensation of movement. Three of the children had shuddering spells prior to onset of head tremor. Two children have developed mild dystonic posturing of the legs when intently concentrating. Their general and neurologic examinations were normal. Normal investigations included brain magnetic resonance imaging and computed tomography, urine amino acids and organic acids screening, serum lactate, erythrocyte sedimentation rate, antinuclear antibodies, and ceruloplasmin and copper levels. A family history of tremor was present in two children, maternal epilepsy in one child, and infantile shuddering occurred in the father of one child. Therapy included trials of selective and nonselective beta-adrenergic blockers, alpha-adrenergic agonists, anticholinergics, anticonvulsants, and amantadine. One child responded well to both timolol and trihexyphenidyl. A second child responded moderately to primidone. Two have not been treated. Two have had head tremor spontaneously remit. We conclude from this small series of children with head tremor that it can evolve from a prior history of shuddering spells, occurs in the context of a positive family history of tremor, and can be accompanied by the development of a mild dystonia. Therapeutic response is variable to multiple agents. Spontaneous remission occurs, suggesting a benign course.

Hereditary neuropathy with liability to pressure palsies in children.

The clinical and neurophysiologic findings of two children presenting with focal weakness and atrophy in unusual nerve distributions and no apparent antecedent injuries are reported. Patient 1 presented with a droopy left shoulder that was initially attributed to scoliosis. Patient 2 presented with right biceps brachii atrophy that was first brought to his parent's attention during a routine physical examination. In addition to documenting focal spinal accessory and musculocutaneous mononeuropathies as the cause of weakness in Patients 1 and 2, respectively, nerve conduction studies also revealed evidence of superimposed diffuse demyelinating polyneuropathy in both children. The latter findings suggested the diagnosis of hereditary neuropathy with liability to pressure palsies and led to definitive DNA diagnoses.

Brain morphometric analysis in neurofibromatosis 1.

RATIONALE AND OBJECTIVES: To investigate the relationships between brain and skull base growth in patients with neurofibromatosis 1 (NF1) compared with healthy control subjects using brain magnetic resonance imaging (MRI) for morphometric analysis. METHODS: Evaluated patients included children who underwent T1- and T2-weighted or dual-echo proton density axial and T1-weighted sagittal brain MRI from January 1, 1988, to December 31, 1995. Study subjects (n = 27) received a diagnosis of NF1 by accepted National Institutes of Health clinical criteria and were compared with an age- and sex-matched control group (n = 43). Twenty-four predetermined ventricular and brain parenchymal dimensions and area calculations were evaluated. Data were analyzed using 2-tailed t tests, chi2 analysis, analysis of variance, and analysis of covariance adjusted for age and sex. Correlational analyses with respect to subject type and age were performed separately. RESULTS: There were 27 patients (20 boys, aged 1.0-17.7 years; mean age, 8.8 years) and 43 controls (22 boys, aged 0.1-17.7 years; mean age, 5.9 years). The mean ages between groups (boys, girls, and totals) were not statistically different. Significant differences were appreciated for 6 of 24 measures. Patients with NF1 had a significantly larger bicaudate width (P = .002), biatrial width (P<.001), and biparietal diameter (P = .003), but not hemispheric length. They also had significantly increased iter measures (P = .004), descending sigmoid sinus (P<.001), and an age-specific increase in brainstem height (P = .03) not seen in controls. CONCLUSIONS: Patients with NF1 experience dynamic changes in brain morphometry, resulting in a predominant lateral volume expansion of the supratentorial compartment and an increasing velocity of brainstem growth as they age. These data underscore brain-region-specific parenchymal overgrowth potential.

Electroencephalographic findings in ornithine transcarbamylase deficiency.

A 3-day-old infant presented with anorexia, irritability, hypotonia, and seizures. Blood ammonia was 2115 micromol/L and amino and organic acid analyses were consistent with ornithine transcarbamylase deficiency. Liver biopsy confirmed only 1% enzyme activity. The patient was treated with hemodialysis. An electroencephalogram (EEG) revealed multifocal independent spike-and-sharp-wave discharges. After initial stabilization he was placed on a low-protein diet with citrulline and phenylbutyrate. Conjugating agents (arginine, sodium benzoate, and sodium phenylacetate) have been added during periods of metabolic decompensation. Although developmentally delayed, the patient has shown signs of clinical improvement and EEG activity has likewise improved with only mild background slowing and no evidence of epileptogenic activity at 4 years of age. A second infant presented at 3 days of age with a similar history, blood ammonia of 1382 micromol/L, and metabolic studies indicative of ornithine transcarbamylase deficiency. EEG showed multifocal independent ictal and interictal discharges. Electrographic abnormalities persisted despite lowering of blood ammonia with hemodialysis and conjugating agents. The patient continued to decline clinically and died on the 7th hospital day. EEG changes parallel the clinical course of ornithine transcarbamylase deficiency and may serve as an objective marker of the effectiveness of therapeutic interventions.

Tuberous Sclerosis Consensus Conference: recommendations for diagnostic evaluation. National Tuberous Sclerosis Association.

At the recent Tuberous Sclerosis Consensus Conference, a subcommittee proposed recommendations to guide the rational use of diagnostic studies in patients with tuberous sclerosis complex. Recommendations were made for diagnostic evaluation at the time of diagnosis, when testing helps both to establish the diagnosis and to identify potential complications. Additional guidelines were proposed for the ongoing surveillance of established patients to detect later complications of tuberous sclerosis complex. In the absence of comprehensive population studies to govern the use of diagnostic studies in individuals with tuberous sclerosis complex, the panel developed guidelines based on the disorder's natural history, concentrating on complications that are common, clinically significant, and more easily managed when found early. Finally, the group made suggestions for the use of diagnostic tests to identify family members who have tuberous sclerosis complex. Although these recommendations should standardize and improve our use of diagnostic studies in individuals with tuberous sclerosis complex, the clinical approach in a given patient must remain flexible enough to meet the needs of individual patients and families.

Respiratory sinus arrhythmia of brainstem lesions.

In this pilot study we investigated the hypothesis that intrinsic and extrinsic brainstem lesions situated within the pontomedullary region would effect the integrity of respiratory sinus arrhythmia. The study sample consisted of three patients with anatomic brainstem abnormalities associated with isolated Chiari I malformation, Chiari II malformation with syringobulbia, and achondroplasia with cervicomedullary compression. They were compared to an age- and sex-matched control group of nine patients. Each subject's electrocardiogram was recorded in a quiet room and digitized by a personal computer during five 1-minute periods. R-R intervals within each 1-minute period were converted to heart rate in 120 successive 0.5-second intervals. The resultant heartrate time series was converted to its underlying frequency composition by a fast Fourier transform and averaged across minutes. Respiratory sinus arrhythmia was defined as the variability in the time series over a frequency range (0.096 to 0.48 Hz) corresponding to a range of respiratory rates from 6 to 30 breaths per minute. Analysis revealed a significant reduction in respiratory sinus arrhythmia (P < .05), defined as the summated area under the curve, with a mean for controls of 35.42+/-28.13 SD and for subjects of 17.20+/-11.50 SD. There was a gradient of abnormality noted, with the mildest deviation in respiratory sinus arrhythmia for the patient with isolated Chiari I malformation and maximum deviation seen in the patient with extrinsic cervicomedullary compression.

Cervicomedullary astrocytoma simulating a neuromuscular disorder.

A 12-year-old male developed progressive proximal upper extremity weakness over a 3- to 4-year period. The clinical findings of proximal upper extremity weakness and atrophy, prominent scapular winging, and no sensory deficits or upper motor neuron signs suggested a neuromuscular disorder. Electromyography was consistent with a chronic denervating disorder involving the upper cervical anterior horn cells or their axons. A cervical magnetic resonance image revealed a large intramedullary mass extending from the inferior aspect of the fourth ventricle down to the level of T2. A biopsy of the lesion was consistent with a low-grade astrocytoma.

Respiratory sinus arrhythmia in children with severe cyanotic and pallid breath-holding spells.

In this study we investigated centrally mediated parasympathetic regulation of modulated cardiac vagal tone among children with severe cyanotic and pallid breath-holding spells by examining respiratory sinus arrhythmia. Respiratory sinus arrhythmia was evaluated in 41 children; 17 subjects with cyanotic breath-holding spells (6 boys, 11 girls; mean age 37.1 months), 7 subjects with pallid breath-holding spells (2 boys, 5 girls; mean age 33.0 months), and 17 controls (8 boys, 9 girls; mean age 41.2 months). Subjects had recurrent (more than 3) severe breath-holding spells. Each subject's electrocardiogram was recorded in a quiet room and digitized by an 80386 personal computer during five 1-minute periods. R-R intervals within each 1-minute period were converted to heart rate in 120 successive 0.5-second intervals. The resultant heart rate time series was converted to its underlying frequency composition by a fast Fourier transform and averaged across minutes. Respiratory sinus arrhythmia was defined as the variability in the time series over a frequency range (0.096 Hz to 0.48 Hz) corresponding to a range of respiratory rates from 6 to 30 breaths per minute. ANCOVA adjusting for age and sex was conducted with the subject group as the independent measure. There were no significant differences between subjects with cyanotic breath-holding spells and controls. Pallid breath-holding spell subjects had a marked difference in respiratory sinus arrhythmia from either controls or subjects with cyanotic breath-holding spells, demonstrating less variability in respiratory sinus arrhythmia (P < .042) This study supports the hypothesis that there exists autonomic dysregulation in pallid breath-holding spells, caused by a primary central parasympathetic disturbance distinct from the dysregulation found in cyanotic breath-holding spells.

Magnetic resonance imaging lesion analysis in neurofibromatosis type 1.

OBJECTIVE: To define the evolution of identified high-signal brain parenchymal lesions on magnetic resonance imaging (MRI) studies in patients with neurofibromatosis type 1 (NF-1). DESIGN: A cohort of patients with NF-1 who underwent MRI were identified prospectively and their imaging studies analyzed. PATIENTS: All referred patients with NF-1 (as defined by National Institutes of Health consensus criteria), who had undergone imaging with MRI were eligible. Of 123 patients with NF-1 whose conditions were evaluated, 30 patients had undergone 59 MRIs. There were 22 males and 8 females, aged 1 to 53 years with mean age of 12.5 years. Two groups of patients were identified, those with brain lesions (WBL) and those with no brain lesions. All initial and subsequently obtained MRIs from the WBL group were analyzed and tallied for number, size, and location of lesions over serial studies. RESULTS: Of the 19 patients with WBL, lesions were in hemispheres in 19 patients, and in the brainstem and the cerebellum in 10 patients each, respectively. Lesions were located in the cerebellum and globus pallidus most often (87 of 129 lesions). Of the patients with WBL having serial studies, a total of 97 lesions equaling 197 units (mean, 2.03 units per lesion) were identified at initial study. Follow-up evaluation (interval, 0.5-4.5 years; mean, 2.3 years), showed a decrease in both total number of lesions (68 [-29%]) and size (132 units; mean, 1.86 units per lesion [-33%]). Importantly, brainstem lesions increased in both number (+36%) and size (+6.4%) over the same intervals in 7 of 13 patients with WBL studied serially, whereas hemispheric and cerebellar lesions were more evanescent. CONCLUSIONS: High-signal T2 lesions on MRI in patients with NF-1 evolve over time. The evolution of the NF-1 lesion is region specific and may relate to preferential region-specific effects of the NF-1 gene product.

Respiratory sinus arrhythmia in children with severe cyanotic breath-holding spells.

In this study we sought to investigate parasympathetic activity among children with severe cyanotic breath-holding spells by examining respiratory sinus arrhythmia. The study sample was composed of two groups of patients, 16 subjects with cyanotic breath-holding spells (5 male, 11 female; mean age, 37.5 mo) and 17 controls (8 male, 9 female; mean age, 37.7 mo). Each subject's electrocardiogram was recorded in a quiet room and digitized by an 80386 personal computer during five 1-minute periods. R-R intervals within each 1-minute period were converted to heart rate in 120 successive 0.5 second intervals. The resultant heart rate time series was converted to its underlying frequency composition by a fast Fourier transform and averaged across minutes. Respiratory sinus arrhythmia was defined as the variability in the time series over a frequency range (0.096-0.48 Hz) corresponding to a range of respiratory rates from 6 to 30 breaths per minute. Analysis revealed after ANCOVA adjustment for age and gender with subject group and frequency bin as dependent measures, that subjects with cyanotic breath-holding spells had similar variability in their heart rates as did controls (group x frequency bin: F = 0.74, P = 0.71). This study supports the hypothesis that autonomic dysregulation in cyanotic breath-holding spells is not due to a primary disturbance in central parasympathetic control over cardiac rate and rhythm.

Family pedigree analysis of children with severe breath-holding spells.

We examined family pedigrees of children with severe breath-holding spells (SBHS). There were 57 probands (27 males, 30 females; 44 cyanotic, 13 pallid) whose families comprised 1683 individuals. We found that 31 (27%) of 114 proband parents and 9 (21%) of 43 proband siblings had current or prior SBHS. Father-to-son transmission was observed in 7 instances. There were 7 families with 2 or more affected siblings and 5 families with 3 or more affected members. From 85 nuclear families, 130 individuals had current or prior SBHS (59 males, 71 females; male/female ratio, 1:12). These data suggest that the most likely underlying genetic inheritance pattern in SBHS is an autosomal dominant trait with reduced penetrance.

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.

Prenatal diagnosis of intracranial lipoma associated with agenesis of the corpus callosum.

BACKGROUND: Lipoma of the corpus callosum is a congenital malformation present in 1:1700 individuals. Only three cases of prenatal sonographic diagnosis have been described. CASES: Two cases of prenatal sonographic diagnosis of intracranial lipoma are described. The first case was visible at 26 weeks' gestation and was associated with partial agenesis of the corpus callosum, a characteristic midline gyral pattern, and fetal colpocephaly. The second case was an isolated lipoma diagnosed at 37 weeks. In both cases transvaginal scanning and color Doppler studies were useful adjuncts in making the diagnosis. CONCLUSION: Prenatal sonographic diagnosis of intracranial lipoma associated with agenesis of the corpus callosum is possible as early as 26 weeks' gestation. Because prognosis depends on associated anomalies, a detailed examination of fetal intracranial anatomy and a complete anatomic survey should be performed. Awareness of this lesion can be expected to increase its detection on prenatal sonography.