Early prediction of neurologic outcome after perinatal depression

Evaluation is presented of whether or not a detailed neuromotor examination at 3 months of age could predict later neurologic abnormalities among term infants with perinatal depression. In a prospective cohort, infants were neurologically evaluated at 3 and 12 months. Infants were scored from 0 to 5 according to a new neuromotor scoring system. The neuromotor score at 3 months (NMS-3) was compared with the NMS at 12 months (NMS-12). Seventy-four infants were enrolled in the study; nine were lost to follow-up, and five died before reaching 1 year. Sixty infants were examined (neurologic abnormalities = 52%, normal = 48% at 1 year). The NMS-3 correlated strongly with the NMS-12 and the results of the 12-month neurologic examination. All infants with a NMS-3 of 5 had neurologic abnormalities at 1 year. Infants with neonatal seizures had a significantly increased risk of developmental abnormalities at 1 year. Eighteen infants exhibited transient abnormalities. Using a simple scoring system, the results of the early neurologic examinations correlated strongly with outcome among term infants with perinatal depression. A subgroup of infants had transient abnormalities. These findings suggest that in term high-risk infants, the 1-year neurologic outcome can be predicted at 3 months of age using these parameters.     

Abnormal neurologic maturation in adolescents with early-onset schizophrenia

OBJECTIVE: This study evaluated neurologic functioning in adolescents with schizophrenia with onset of psychosis before age 13. METHOD: The authors administered a structured neurologic examination to 21 adolescents with early-onset schizophrenia and 27 healthy age- and sex-matched comparison subjects. RESULTS: The adolescents with schizophrenia had a high frequency of neurologic abnormalities. Neurologic signs decreased with age in the healthy comparison subjects but not in the subjects with schizophrenia. CONCLUSIONS: The adolescents with schizophrenia had a high burden of neurologic impairment and a pattern of abnormalities similar to that of adults with schizophrenia. The persistence of neurologic signs in the adolescents with schizophrenia, which faded with age in the healthy comparison adolescents, supports earlier evidence of a delay in or failure of normal brain development during adolescence.     

Computed tomography and childhood seizure disorders

Computerized tomography (CT) was performed on 256 children with seizure disorders. The incidence of abnormal scans was closely related to seizure type, and permitted separation of patients into a low-yield and a high-yield group. Low-yield groups included children with idiopathic generalized seizures, children in whom both the neurologic examination and electroencephalogram (EEG) were normal, and children with a generalized seizure of unknown etiology in whom the neurologic examination and the EEG were normal. The high-yield groups included children with partial seizures with elementary symptomatology, partial seizures with complex symptomatology, generalized seizures with known etiology, neonates with seizures, and children whose seizures began as neonates. The overall incidence of abnormalities in the entire group was 33 percent. An abnormal neurologic examination increased the incidence of abnormal CT scans to 64 percent. EEGs were abnormal in 65 percent of the children, but only focal slowing resulted in a significant increase in the incidence of abnormal CT scans. Seven children (2.7 percent) had intracranial abnormalities requiring surgery. If the neurologic examination and EEG were normal, the yield of abnormal CT scans was only 5 percent of the total.     

Neurologic and evoked potential abnormalities in subtle cobalamin deficiency states, including deficiency without anemia and with normal absorption of free cobalamin

The meaning of a low serum cobalamin level when the classic findings of pernicious anemia are lacking is undergoing reevaluation. We therefore studied the neurologic status of 11 patients who had low cobalamin levels without definite hematologic evidence of deficiency. Neurologic evaluation included pattern-shift visual and median and posterior tibial nerve somatosensory evoked potentials. None of the patients had megaloblastic changes in the blood or bone marrow, although 7 of the 11 had subtle cellular cobalamin disturbances demonstrated by an abnormal deoxyuridine suppression test result. Seven patients had normal Schilling test results and 2 had borderline results; however, 2 of the 5 patients tested further had food-cobalamin malabsorption, while a third had prepernicious anemia. The patients displayed a variety of neurologic problems, including dementia, depression, myelopathy, neuropathy, and seizure disorder; 1 patient was neurologically normal by clinical criteria. Evoked potential abnormalities were demonstrable in 8 of the 9 patients with subtle cobalamin deficiency, and in at least 5 cases the disturbance was central. In contrast, both patients whose low serum cobalamin levels were found on evaluation to be spurious had normal evoked potentials. Evoked potential abnormalities improved in the one patient retested after cobalamin therapy. These findings demonstrate that neurologic deficits occur not only in classic cobalamin deficiency but also in subtle or atypical cobalamin deficiency states in which anemia is absent and Schilling test results are normal. Electrophysiologic evidence of neurologic impairment is often present, even in patients without obvious clinical neurologic abnormalities.     

Association between electroencephalographic findings and neurologic status in infants with congenital heart defects.

Neurologic status is of concern in infants with congenital heart defects undergoing open heart surgery. The association between perioperative electroencephalography (EEG) with acute neurologic status and subsequent outcome was examined in a cohort of 60 infants. Preoperative EEG and neurologic examinations were performed within 1 to 2 days prior to surgery (n = 27) and postoperatively (n = 47). Prior to surgery, 15 of 27 infants had normal EEG, whereas 5 had epileptiform activity and 9 had disturbances in background activity that were primarily moderate (8/9) and diffuse (7/9). Postoperatively, only 17 of 47 infants had normal recordings. Newborns (<1 month) were more likely (P< .001) to demonstrate EEG abnormalities than infants. Epileptiform activity was documented in 15, whereas 28 had background abnormalities that were moderate-severe (22/28) and diffuse (20/28) in most. Epileptiform activity prior to surgery was always associated with an abnormal neurologic examination, and this association persisted postoperatively (86%). Moderate to severe background abnormalities in the postoperative EEG was also strongly associated with acute neurologic abnormalities (93%). Severe background abnormalities (n = 5) were 100% predictive of death or severe disability. Long-term follow-up revealed that all children with normal postoperative EEGs had positive neurologic outcomes (P = .04); however, there were many false positives. Perioperative EEG abnormalities increased the likelihood for acute neurologic findings, whereas normal recordings following surgery were reassuring with regard to a favorable outcome.     

Pediatric Chiari I malformations: do clinical and radiologic features correlate?

BACKGROUND: Although Chiari I malformation is increasingly recognized in children, little is known about its clinical presentation in this age group. OBJECTIVE: To evaluate the relationship between clinical and MRI features of pediatric Chiari I malformations. METHODS: We performed a chart review and MRI analysis of 49 children with Chiari I malformation. The degree of tonsillar ectopia was compared with age at onset, presence of syringomyelia, and a neurologic severity score as follows: asymptomatic = 0, symptomatic with normal neurologic examination = 1, and symptomatic with abnormal examination = 2. RESULTS: Age at onset of symptoms ranged from 10 months to 14 years. Fifty-seven percent of patients were asymptomatic. Headache and neck pain were the most frequent complaints. Syringomyelia was detected in 14% of patients and skull base abnormalities in 50%. The magnitude of tonsillar ectopia (5 to 23 mm) correlated with severity score (p = 0.04) but not with other clinical measures. CONCLUSIONS: The clinical symptoms of Chiari I malformations in children are nearly identical to those seen in adults. Children with greater amounts of tonsillar ectopia on MRI are more likely to be symptomatic.     

Transient neurologic abnormalities and BAEPs in high-risk infants

We examined brainstem auditory evoked potentials in 2 neurodevelopmentally different groups of high-risk premature infants during the first year of life. Our 77 patients were considered at birth to be at risk for neurologic disabilities, but were found to have normal development in the second year of life. The patients were divided into 2 groups on the basis of their neurologic findings during the first year of life; 24 of the 77 patients demonstrated transient neurologic abnormalities (group I) and the remaining 53 demonstrated normal neurologic findings through the first year of life (group II). Normative data of brainstem auditory evoked potentials were obtained from 60 low-risk and neurologically normal infants. Group I patients had prolonged III-V and I-V intervals at 2 months of age or younger and poorly detectable waves VI and VII at 5 months of age or younger, compared with control subjects. Wave VI was poorly detected in group II patients only at 35-39 weeks of conceptional age. Brainstem auditory evoked potentials suggested that the patients with transient neurologic abnormalities had transient dysfunction or maturational delay in the brainstem and upper auditory pathway early in the first year of life.     

Magnetic resonance imaging in puerperal seizures: Postpartum eclampsia or cerebral venous thrombosis?

We reviewed cranial magnetic resonance imaging (MRI) studies in three women with puerperal seizures. One patient had eclampsia and had extensive parasagittal abnormalities on MRI, but she had a normal neurologic examination and recovered without sequelae. The other patients presented with postpartum seizures but were not eclamptic. Both of these women also had parasagittal abnormalities on MRI, which were less severe than the patient with eclampsia. However, both of these patients had neurologic sequelae. One woman had persistent headaches; the other had persistent seizures. In both of these women, EEG showed persistent epileptiform abnormalities. Convalescent MRI was normal in all three patients. Contrary to recent reports, we suggest that cranial MRI in women with puerperal seizures is not specific for eclampsia and does not necessarily predict the clinical course.     

Clinical significance of plantar grasp response in infants

The present study was undertaken to delineate the clinical significance of the plantar grasp response in infants. All 834 normal control infants had a positive response within the first 6 months of age, and most of them had a marked response at 1-4 months of age. The authors attempted to evaluate the neurologic outcomes of infants who had negative or diminished responses in these respective periods. Ninety-three infants examined from 1982 to 1992 fulfilled these criteria, and their prognoses were reviewed. The outcomes consisted of cerebral palsy in 75 (69 spastic, four athetoid with spasticity, one athetoid, and one ataxic); mental retardation in seven; borderline intelligence in two; motor delay in one; and eight were considered normal. These outcomes indicate that the negative or diminished response of this primitive reflex during early infancy is highly suggestive of neurologic abnormalities, especially for spasticity. Infants with such findings should be carefully observed for possible development of neurologic abnormalities.     

One-year follow-up of infants with abstinence-associated seizures

Fourteen infants with neonatal abstinence-associated seizures were assessed neurodevelopmentally during the first year of life. Despite abnormal neurologic examination results in eight of 12 infants at 2 to 4 months of age, nine of 12 infants had normal neurologic examination results at follow-up (two infants were unavailable for follow-up; one infant died of acquired immunodeficiency syndrome). Nine neonatal electroencephalograms were abnormal; seven of eight of these abnormal tracings normalized during the follow-up period. Bayley developmental scores remained normal during the first year of life and did not differ from either passively addicted infants without seizures or from published population norms. This short-term favorable prognosis for abstinence-associated seizures differs from that associated with neonatal seizures due to other causes. This observed improvement in neurologic function may be based on replenishment of neurotransmitters following transient depletion in the neonatal period.     

Electroencephalographic abnormalities in children with congenital heart disease

Ninety-eight consecutive patients with clinically suspected congenital heart disease were prospectively studied with electroencephalographic (EEG) recordings before cardiac catheterization. Twenty-five patients had abnormal EEGs. Fifty-five patients had acyanotic heart disease and normal neurologic examination results, of whom 15 had abnormal EEGs. Thirteen had spikes or spike and wave discharges and two had mildly abnormal EEGs. Twenty-seven patients had cyanotic heart disease and normal neurologic examination results, of whom four had abnormal EEGs. Seven patients (8%) had abnormal neurologic examination results, of whom four had abnormal EEGs. There was a higher incidence of seizures with increasing age. Based on their medical history two children with acyanotic heart disease had had seizures without EEG abnormalities. Five children with normal catheterization findings and four children with Down's syndrome (two with abnormal EEGs) were excluded from the total of 98. These findings suggest that subclinical nervous system involvement may occur in congenital heart disease.     

Prognostic significance of multimodality evoked response testing in high-risk newborns

Exposure to hypoxic-ischemic events in fetal or neonatal life may lead to permanent brain damage and subsequent neurodevelopmental deficits. Clinical and diagnostic tools have been somewhat helpful in identifying an at-risk group, particularly those patients sustaining significant neurologic sequelae. In this prospective study, the prognostic significance of multimodality evoked responses in high-risk newborns was examined. A group of 44 high-risk newborns, as well as 14 healthy newborns, were tested during the newborn period with auditory brainstem responses and somatosensory evoked responses; these tests were repeated at 2 and 6 months corrected age. A neonatal neurologic examination, the Einstein Neonatal Neurobehavioral Assessment Scale, was also conducted. At 1 year corrected age, both groups were assessed in a blind fashion by a pediatric neurologist and a psychologist to determine neurodevelopmental outcome. Results indicated that somatosensory evoked response abnormalities in particular predict an abnormal neurologic status at 1 year of age. Abnormalities that persisted or worsened correlated with severe neurologic impairment, whereas an abnormal somatosensory evoked response that improved or normalized in infancy was associated with mild to moderate neurologic sequelae. Increased brainstem conduction in the auditory brainstem responses was also associated with neurologic sequelae. Normal findings from auditory brainstem responses and somatosensory evoked responses predicted normal developmental scores in all areas, as well as a normal neurologic outcome at 1 year with negative predictive powers ranging from 85–100%. Evoked response testing appears to be an important adjunct to the neurologic investigation of high-risk newborns.     

Neurologic symptoms in children with systemic lupus erythematosus

Neurologic complications of systemic lupus cerebritis are not as well known in children as in adults. Twenty-five children with neurologic complications were identified after reviewing the hospital medical records of 86 children with systemic lupus erythematosus. Seven children (28%) had neurologic symptoms at the time of initial diagnosis of systemic lupus erythematosus; median time between diagnosis of systemic lupus erythematosus and onset of neurologic complications was 1 month (range 0-5 years). Seizures were the most common neurologic symptoms overall, but headaches were the most frequent neurologic manifestation in children without a previous diagnosis of systemic lupus erythematosus. Sixteen children had seizures, and 12 children had seizures as the initial central nervous system involvement. Almost all children who developed seizures had an established diagnosis of systemic lupus erythematosus; only one child had seizures that led to the diagnosis of systemic lupus erythematosus. No patient had status epilepticus, and, in general, seizures were not difficult to control. In six children, headache was the initial symptom of central nervous system involvement. Five children had lupus cerebritis, three children had stroke, and two had isolated cranial neuropathies. Chorea was seen in only two cases, and three children had pseudotumor cerebri. Treatment with high-dose intravenous methylprednisolone led to a good response in 18 children; cyclophosphamide was required in 6 patients and plasmapheresis in 1 child. Outcome was generally good, although one child developed fulminant cerebritis with intracranial hypertension and died.     

Assessment of median nerve somatosensory evoked potentials in cerebral ischemia

Seventy patients with cerebral ischemia (21 with transient ischemic attack and 49 with stroke) were studied with short-latency median nerve somatosensory evoked potentials to characterize the evoked potentials in all ischemic patients and to investigate their efficacy for prognosis in stroke. Within 72 hours of symptom onset, all 70 patients received a scaled neurologic function score, with a maximum of 50 points. Somatosensory evoked potential abnormalities were found in 10% (2/19), 42% (15/36), and 93% (14/15) of all patients with initial neurologic examinations who had normal (50 points), mild-moderate (30-49 points), and severe deficits (less than or equal to 29 points), respectively. Thirty-seven of the 49 stroke patients were available for a follow-up neurologic assessment. Eight-nine percent (8/9) of the stroke patients with poor outcome had somatosensory evoked potential abnormalities; 82% (9/11) of the stroke patients with severe neurologic deficits at onset had poor outcome. Results demonstrate that somatosensory evoked potential abnormalities are common in patients with cerebral ischemia but that somatosensory evoked potential findings are not significantly better than a detailed neurologic examination in predicting outcome from stroke.     

Adult myoclonic epilepsy: a distinct syndrome of idiopathic generalized epilepsy

The authors present 11 cases of idiopathic generalized epilepsy that began in adulthood at a mean age of 39 years. All patients had myoclonic jerks, five had absence seizures, and nine had infrequent generalized tonic-clonic seizures. A majority had a family history of seizures. EEG in all patients showed generalized epileptiform abnormalities, whereas neuroimaging and neurologic examination results were normal. This series appears to represent a previously undescribed idiopathic generalized epilepsy syndrome of adult myoclonic epilepsy.     

Agyria-pachygyria: clinical,neuroimaging, and neurophysiologic correlations

Agyria-pachygyria complex is a disorder of neuronal migration and organization. Patients suffer either motor or intellectual retardation. We report our experiences of 10 patients with agyria-pachygyria complex and evaluate their clinical features, electroencephalography, and evoked potentials. Of nine electroencephalography examinations, five patients demonstrated characteristically high-amplitude fast activity. One of nine patients had an abnormal brainstem auditory-evoked potential. Three of seven patients had abnormal goggled visual-evoked potential. Six patients received somatosensory-evoked potential examinations, and five of these were abnormal, including four with prolonged central conduction times. Of the 10 patients, eight survived with variable intellectual and motor retardation; two died of sepsis. Patients with grades 1-4 agyria-pachygyria had high incidences of somatosensory-evoked potential abnormalities and also suffered worse neurologic outcomes. Normal brainstem auditory-evoked potential but abnormal cortical somatosensory-evoked potential components and prolonged central conduction time in these patients indicate that agyria-pachygyria is a supratentorial disease. We conclude that somatosensory-evoked potential examination is supplemental to neuroimaging in predicting the neurologic prognosis of patients with agyria-pachygyria.     

Follow-up study of macrocephalic children with enlargement of the subarachnoid space.

Eighteen macrocephalic children with enlargement of the subarachnoid space (ESAS), with or without mild ventricular dilatation, were followed prospectively to a mean age of 56 months. All were born at term, with uneventful neonatal period and negative tests for congenital infections. There were 17 boys and 1 girl and the mean follow-up period was 46 months (8-58 months). The initial neurologic evaluation, between ages of 2 to 33 months, disclosed abnormalities in 2 cases. At the follow-up one was still abnormal and the other had a normal neurological examination. Another child, who had a normal neurological examination at the age of 5 months, at the age of 7 years and 7 months had an IQ of 77. Thus the abnormality rate at follow-up was 11%. The OFC returned to the normal range in 45% of the children at the follow-up period. There were no cases of intracranial hypertension. One infant had subdural taps performed at the age of 13 months that disclosed a fluid with the same characteristics as the CSF. All the children had a CT-scan performed at the beginning of the study that revealed a large subarachnoid space; in 77% it was associated with mild ventricular dilatation. Eleven had CT-scans repeated, during the study period, which showed resolution of the process in 3 cases, improvement in 2, and unchanged in 6. We conclude that enlargement of the subarachnoid space in macrocephalic children is often a benign entity. ESAS and macrocephaly will still be present in the majority of children in the long-term follow-up.     

Somatosensory evoked response abnormalities in high-risk newborns

In a previous study from our laboratory, the prognostic significance of the auditory brainstem evoked response was assessed in high-risk neonates. An abnormal auditory brainstem evoked response predicted neurologic deficits at age 1 year; however, a normal result did not predict a normal outcome. In order to evaluate the prognostic utility of examining other sensory pathways, somatosensory evoked responses were elicited following median nerve stimulation. Testing was performed at 37–44 weeks conceptional age (defined as gestational age plus chronologic age) and at 2 and 6 months conceptional ages. Those patients studied included 34 high-risk neonates and 18 healthy, term infants as controls. Ten of the 34 patients had abnormal somatosensory evoked responses. Abnormalities included increased absolute (N19, P22) and interwave (N13–N19, N19–P22) latencies and flat potentials, alone or in combination. Three children with flat potentials demonstrated a persistence of this abnormality on subsequent examination and they later presented clinically with spastic quadriparesis. Four infants with increased latencies manifested normal responses on subsequent examination. Recently, these 4 patients exhibited tone abnormalities and mild developmental deficits; developmental outcome, however, will be assessed in a blind study at 1 year of age as part of this ongoing prospective study. Preliminary results suggest that somatosensory evoked responses may be valuable as an electrophysiologic predictor of outcome.     

Spectrum of central nervous system abnormalities in neurocutaneous melanocytosis

Aim Neurocutaneous melanocytosis is a rare neurocutaneous syndrome defined by the presence of large and/or multiple congenital cutaneous nevi and melanocytic deposits in the central nervous system. We sought to define the spectrum of central nervous system abnormalities in children with neurocutaneous melanocytosis. Method We retrospectively reviewed cases of neurocutaneous melanocytosis referred to the pediatric neuro‐oncology service at our center from 2003 to 2010. Results Of 14 patients (11 males, 3 females) identified, eight were living. Median age of survivors was 31 months (range 12mo–6y 10mo) while median age of death was 81 months (19mo–28y). Of the six patients who died, all had diffuse leptomeningeal melanocytic deposits and four had leptomeningeal melanoma. All patients had neuroimaging: six had findings suggestive of diffuse leptomeningeal melanocytosis; seven had multifocal melanocytic deposits; and one patient had normal neuroimaging but focal seizures. Spinal abnormalities were common: three patients had extensive dorsal spinal arachnoid cysts and one had a benign cervical spindle cell tumor. Seven patients had epilepsy. Three patients had profound developmental delay; the other 11 patients had no or mild delay. Interpretation Children with neurocutaneous melanocytosis exhibit a wide range of intracranial and intraspinal abnormalities and variable clinical outcomes.     

Spectrum of cerebrospinal fluid findings in various stages of human immunodeficiency virus infection

This report summarizes the results of neurologic and cerebrospinal fluid (CSF) study findings in over 400 of the 649 human immunodeficiency virus-infected US Air Force personnel, evaluated as of Dec 31, 1987. Eighty percent of these patients were entirely asymptomatic and immunologically normal, 13% had low T-helper lymphocyte counts and/or cutaneous anergy, and only 7% had opportunistic infection. Sixty-three percent of all patients had some CSF abnormality. Sixty percent of the asymptomatic group had at least one abnormal result, over 25% had three or four CSF abnormalities, and over 7% had five or six abnormal values. When patients with evidence of blood-brain barrier leak were excluded, significant differences were seen between disease groups with regard to CSF glucose, CSF IgG levels, and CSF IgG synthesis. No human immunodeficiency virus-related central nervous system abnormalities were found on neurologic examination in immunologically intact asymptomatic patients regardless of CSF findings. No clear-cut predictor of impending central nervous system complications has, as yet, been identified from the CSF parameters studied.