Sacral agenesis and neurogenic bladder: Long-term outcomes of bladder and kidney function.

BACKGROUND: Sacral agenesis (SA) is a rare congenital condition that refers to the absence of part or all of two or more lower sacral vertebral bodies. It can be associated with neurogenic bladder dysfunction that does not necessarily correlate with the level of spinal or skeletal defect. Patients with SA should undergo urodynamic studies (UDS) to guide lower urinary tract (LUT) management. OBJECTIVE: This review aimed to update the present institutional experience since 1981 of this rare patient population with detailed, long-term follow-up of bladder and kidney function. STUDY DESIGN: A single institution, retrospective, IRB-approved review was performed on patients born after January 1, 1981 with an isolated diagnosis of sacral agenesis without spina bifida, and followed with urologic involvement at Boston Children's Hospital. Records were reviewed for demographics, radiologic imaging, UDS including cystometrogram (CMG) and electromyography (EMG), surgery, and blood chemistries. Comparisons were made between groups of patients based on age at diagnosis, with specific focus on renal function and stability of neurogenic bladder lesion. RESULTS: Forty-three patients were identified: 23 female and 20 male. Thirty-seven children (86%) had a known age of diagnosis. Nineteen were diagnosed before 2 months old, including five who were diagnosed prenatally, 11 were diagnosed between 2 and 18 months, and seven were diagnosed after 18 months. All 43 had UDS, with 24 (55.8%) studied at the time of diagnosis (Summary Table). Twenty had serial full UDS, with 30% demonstrating neurourologic instability. None developed end-stage renal disease (ESRD) or required spinal cord detethering. DISCUSSION: Many children with SA appeared to be diagnosed prenatally or early in life; SA was mostly identified during evaluation of associated anomalies. Though UDS aid in urologic management, testing was not routinely utilized at the time of diagnosis. CONCLUSIONS: This review of long-term follow-up in SA patients showed stable LUT and renal function, with minimal risk of progression to ESRD.

Lateralized cognitive dysfunction in patients with systemic lupus erythematosus.

This study was designed to determine whether there is a lateralized pattern of cognitive dysfunction in patients with systemic lupus erythematosus (SLE). Fifty right-handed patients with SLE, but no history of cerebrovascular disease participated in the study. Thirty right-handed healthy subjects matched for age and education served as controls. SLE and healthy control subjects underwent a three-hour neuropsychological evaluation designed to measure attention, memory, visual spatial skills, verbal skills reasoning, psychomotor speed, and motor function. A cognitive disability index was created to identify cognitive impairment. Percentile tables based on the performance of all subjects were constructed for 20 component scores. Any subject with five or more component scores below the 25th percentile was designated impaired. Using this criterion, cognitive impairment was identified in 50% of patients with SLE and 20% of healthy controls. Patients with SLE were impaired on measures of psychomotor speed/fluency, verbal speed/fluency and verbal memory. This pattern of performance on neuropsycholgical testing was consistent with left hemisphere brain dysfunction. The observed deficits were not clearly attributable to vascular lesions and suggest immune-mediated effects on specific brain regions in a subgroup of patients with SLE.

The teratogenicity of anticonvulsant drugs.

BACKGROUND: The frequency of major malformations, growth retardation, and hypoplasia of the midface and fingers, known as the anticonvulsant embryopathy, is increased in infants exposed to anticonvulsant drugs in utero. However, whether the abnormalities are caused by the maternal epilepsy itself or by exposure to anticonvulsant drugs is not known. METHODS: We screened 128,049 pregnant women at delivery to identify three groups of infants: those exposed to anticonvulsant drugs, those unexposed to anticonvulsant drugs but with a maternal history of seizures, and those unexposed to anticonvulsant drugs with no maternal history of seizures (control group). The infants were examined systematically for the presence of major malformations, signs of hypoplasia of the midface and fingers, microcephaly, and small body size. RESULTS: The combined frequency of anticonvulsant embryopathy was higher in 223 infants exposed to one anticonvulsant drug than in 508 control infants (20.6 percent vs. 8.5 percent; odds ratio, 2.8; 95 percent confidence interval, 1.1 to 9.7). The frequency was also higher in 93 infants exposed to two or more anticonvulsant drugs than in the controls (28.0 percent vs. 8.5 percent; odds ratio, 4.2; 95 percent confidence interval, 1.1 to 5.1). The 98 infants whose mothers had a history of epilepsy but took no anticonvulsant drugs during the pregnancy did not have a higher frequency of those abnormalities than the control infants. CONCLUSIONS: A distinctive pattern of physical abnormalities in infants of mothers with epilepsy is associated with the use of anticonvulsant drugs during pregnancy, rather than with epilepsy itself.

Prevalence of migraine in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of migraine in patients with systemic lupus erythematosus (SLE), and to examine the relationships between headache type and other clinical, serologic, and treatment features of the disease. BACKGROUND: Headaches are common in SLE and are a significant source of patient disability. The exact prevalence of headaches in patients with SLE is unknown. The classification of headache syndromes in SLE is also unclear. Previous studies were based on small numbers of patients and the headache types and criteria to define headache types varied widely. METHODS: Four hundred fourteen patients meeting American College of Rheumatology criteria for the diagnosis of SLE were sent the University of California, San Diego Migraine Questionnaire. Patients who completed the questionnaire had their medical records reviewed for constitutional, respiratory, cardiac, vascular, skin, musculoskeletal, other neuropsychiatric, hematologic, renal, and immunologic manifestations of the disease. Recent corticosteroid, nonsteroidal anti-inflammatory drug, antimalarial, and immunosuppressive medications were also recorded. RESULTS: One hundred eighty-six patients completed the questionnaire. Sixty-two percent of patients reported headaches: 39% met diagnostic criteria for migraine and 23% met criteria for nonmigrainous headache. Of the patients with migraine, 56% met criteria for migraine without aura and 44% met criteria for migraine with aura. There were no significant associations between headache type and other clinical, serologic, or treatment features of the disease. CONCLUSIONS: There is a high prevalence of migraine in patients with SLE, and patients should be routinely evaluated for migraine symptoms.

Long-term followup of newborns with myelodysplasia and normal urodynamic findings: Is followup necessary?

PURPOSE: A subset of newborns with myelodysplasia have normal bladder function on urodynamic assessment. We analyzed long-term followup in this population to determine the necessity for subsequent urological surveillance. MATERIALS AND METHODS: We retrospectively analyzed the records of 25 of 204 newborns (12%) with myelodysplasia in whom neurourological evaluation was normal after surgical repair of the spinal defect. Initial assessment included complete urodynamic study, renal ultrasound, urinalysis and urine culture. These patients were reevaluated every 3 months until age 3 years, semiannually until age 6 years and yearly thereafter. The longest followup was 18.6 years. RESULTS: Of the 25 newborns 22 had myelomeningocele and 3 had meningocele. During a mean followup of 9.1 years urodynamics subsequently showed neurourological deterioration in 8 children (32%). No changes in urodynamics were observed in any patient older than 6 years. All children with neurourological deterioration underwent magnetic resonance imaging, which confirmed a tethered spinal cord that was then surgically corrected. After the untethering procedure 2 patients (25%) regained normal voiding function, whereas in 6 (75%) mild or moderate neurogenic bladder dysfunction persisted. CONCLUSIONS: Newborns with myelodysplasia and initially normal urodynamic studies are at risk for neurological deterioration secondary to spinal cord tethering, especially during the first 6 years of life. Close followup of these children is important for the early diagnosis and timely surgical correction of tethered spinal cord, and for the prevention of progressive urinary tract deterioration.

Lateralized EEG findings in patients with neuropsychiatric manifestations of systemic lupus erythematosus.

Routine and quantitative EEG were used to determine whether there is a lateralized pattern of electrophysiologic dysfunction in patients with diverse neuropsychiatric manifestations of SLE. Twenty consecutive patients with neuropsychiatric symptoms of SLE underwent 20-minute EEG recordings with an 18-channel polygraph. Ten 1-second intervals were randomly selected for each patient. Once selected, the intervals were analyzed for the presence of theta and delta slow activity. Mapping was done by four-point interpolation around the 18 acquired data points. On routine EEG, abnormalities were identified in 14/20 patients with SLE. In 12/14 patients, the abnormalities were localized to the left temporal region. Quantitative EEG analyses revealed theta and delta slow activity predominantly affecting the left hemisphere in 16/19 patients with SLE. Taken together, these findings suggest selective involvement of the left hemisphere in patients with diverse neuropsychiatric manifestations of SLE.

Intelligence and physical features of children of women with epilepsy.

The teratogenicity of maternal epilepsy has been attributed to several factors, including the antiepileptic drugs taken to prevent seizures during pregnancy, the occurrence of seizures during pregnancy, and the factors in the mother that caused her to have epilepsy. We have addressed the hypothesis that the children of women who have a history of epilepsy (seizure history), but who took no antiepileptic drugs (AED) and had no tonic-clonic seizures in pregnancy, have an increased risk of malformations and diminished intelligence. The frequency of cognitive dysfunction was determined in 57 seizure history and 57 matched control children aged 6-l6 years. The masked evaluation of the children included a physical and neurologic examination and testing with the Wechsler Intelligence Scale for Children-Revised (WISC-R) and a systematic physical examination for the features of the fetal AED syndrome. The evaluation of both parents of each child included a test of reasoning (Ravens Progressive Matrix) and a physical examination. There were no differences between the two groups of children in either IQ scores or physical features; none of the seizure history children was judged to have the "anticonvulsant face" or digit hypoplasia. This study had 80% power to rule out a difference of seven or more IQ points between the two groups, based on a two-sided test at a 5% level of significance. Our confidence in concluding that there was no difference between seizure history and control infants was strengthened by the fact that no statistically significant differences were observed with respect to multiple outcomes, including eight related measures of intelligence. Thirty (53%) of the seizure history mothers resumed taking AED after the birth of the child we evaluated. Additional studies are needed to address the teratogenicity of the antiepileptic drugs as monotherapy.

Clozapine-induced seizures and EEG abnormalities in ambulatory psychiatric patients.

OBJECTIVE: To examine the seizure characteristics and electroencephalogram (EEG) abnormalities in psychiatric patients taking clozapine, given the estimate of a 10% cumulative risk of generalized seizures in this population. DESIGN: We reviewed all consecutive EEGs of ambulatory psychiatric patients taking clozapine performed at our laboratory during 1996 and 1997. SETTING: A university-affiliated urban teaching hospital. SUBJECTS: Twelve patients (4 F/8 M; mean age 40.1 y, range 20-63) had either presented with de novo ictal events within the first month of clozapine therapy (n = 8) or had EEGs recorded to assess seizure risk (n = 4). RESULTS: According to clinical history and interictal EEG findings, the patients were subdivided as follows: three patients with generalized tonic-clonic seizures, two with generalized myoclonic jerks (1 associated with simple partial seizures), two with complex partial seizures, and one with simple partial seizures. The EEGs revealed interictal epileptiform abnormalities (IEDs) in eight patients, two of whom had not had seizures. IEDs were focal or multifocal, with a predominance of left temporal foci. One patient showed a paroxysmal response to photic stimulation. CONCLUSIONS: Patients taking clozapine may be prone to partial seizures and focal EEG abnormalities as well as to generalized seizures and EEG abnormalities, as previously reported.

EEG abnormalities in systemic lupus erythematosus.

The medical records of 478 SLE patients were reviewed. Ninety-five patients (19.9%) with a history of seizures were identified. EEG reports were available on 62. EEGs were interpreted as normal in 8 (12.9%) and abnormal in 54 (87.1%). Abnormal EEGs were reviewed for the presence of unilateral and bilateral abnormalities. Left hemisphere abnormalities were identified in 43 (79.6%), right hemisphere abnormalities in 4 (7.4%), and bilateral abnormalities in 7 (13.0%) patients with SLE. Abnormalities included theta and delta slowing and sharp wave activity. In 32 of the 43 (74.4%) patients with left hemisphere abnormalities, the abnormalities were localized to the left temporal leads. These findings suggest selective damage to the left temporolimbic region in patients with SLE.

Paraspinal muscle hematoma after electromyography.

There have been few reports of complications related to electromyography. Needle examination of certain muscles is sometimes avoided in patients taking anticoagulant agents, although no clear guidelines have been established. We describe a patient who was not receiving an anticoagulant and developed a large paraspinal muscle hematoma after routine electromyography. Subsequently, all patients who underwent paraspinal muscle electromyography and were diagnosed with radiculopathy at our institution over a 14-month period were reviewed. From this group, 17 patients were identified who had also underwent MRI of the appropriate spinal levels within 1 week after the needle examination. These images were reviewed for evidence of paraspinal muscle hematomas. Four small hematomas were identified in four different patients. None of these were radiologically significant compared with the large hematoma described in the case report. Radiologically apparent paraspinal hematomas after electromyography are an unusual complication of needle examination and do not appear to have any clinical significance. Nevertheless, the presence of these lesions justifies caution when considering electromyography of paraspinal and other deeper muscles in anticoagulated patients.

The in-training examination in internal medicine.

OBJECTIVE: The In-Training Examination in Internal Medicine (ITE-IM) has been offered to internal medicine trainees annually since 1988 as an instrument for self-assessment. This report outlines the manner in which the test is prepared, reviews the results of annual examinations, and analyzes trends during the past 6 years. DESIGN: Results of each examination were reviewed with regard to the demographic characteristics of persons taking the test, their previous medical training, and their present program affiliations. RESULTS: Then number of residents participating in the ITE-IM has increased steadily over the past 6 years. In 1993, more than 12,000 residents from more than 90% of internal medicine training programs in the United States participated in the examination; the percentage of international medical school graduates taking the examination increased from 27% in 1988 to 47% in 1993. Statistical analyses of each examination have shown it to be reliable, internally consistent, and discriminating. Over the past 6 years, graduates of U.S. medical schools have scored consistently higher than those of international medical schools and schools of osteopathic medicine on all annual examinations. However, in 1993, for residents at all levels of training, the differences in scores between graduates of U.S. medical schools and graduates of international medical schools narrowed substantially. From 1988 to 1993, there has been a trend toward lower scores by every cohort on each subsequent examination. The decreases in scores are most pronounced for graduates of U.S. medical school and those of schools of osteopathic medicine. The lower scores may be caused by either an increased level of difficulty in the examination or decreased knowledge among examinees. CONCLUSIONS: The ITE-IM is a useful instrument to assess the knowledge base of residents and program directors with a reliable evaluation of themselves and their programs in comparison to their national peer groups. It also provides objective data to monitor trends over time in residents' scores and relates them to the changing demographic characteristics of trainees and to innovations in the clinical curricula of internal medicine training programs.

Anticonvulsant teratogenesis: I. A study design for newborn infants.

The basis for the apparent teratogenicity of maternal epilepsy is controversial. Is the critical factor the anticonvulsant drugs taken by the pregnant woman, or the genes which cause the mother's epilepsy? We describe a study design developed to assess these competing theories in a cohort study of newborn infants. We show the feasibility of ascertaining exposed and unexposed infants at several birthing hospitals in one urban area. Between 1986 and 1988, we identified 180 drug-exposed and 218 epilepsy-history infants among 49,403 infants. The rate of exposure to seizure medication was 0.36% and of maternal history of epilepsy was 0.44%. A significant number of infants could not be evaluated because they were missed, ineligible, or either the doctor, nurse or parent refused to participate. Overall, there was a significant increase in major malformations, microcephaly or growth retardation among the drug-exposed infants in comparison to both the epilepsy-history and the unexposed infants. The types of epilepsy and the apparent etiology were the same among women who took anticonvulsants and women with a history of epilepsy but no anti-convulsants during pregnancy. This study must be extended to include a sufficient number of infants exposed to each commonly used drug as monotherapy to allow for a comparison of the effect of each drug on pregnancy outcomes; to provide a comparison of infants whose mothers had a strong family history of epilepsy with infants whose mothers had trauma-induced epilepsy; and to assess the possible impact of the severity of the mothers' disease on the infants.

I-123 iofetamine SPECT scan in systemic lupus erythematosus patients with cognitive and other minor neuropsychiatric symptoms: a pilot study.

Accurate diagnosis of central nervous system (CNS) lupus remains difficult, especially when the manifestations are of subtle cognitive and affective changes. This pilot study reports on the use of I-123 iofetamine single photon emission computerized tomography (SPECT) scans in 18 such patients with documented systemic lupus erythematosus. Eight of the 18 scans were abnormal (44%), four in a diffuse bi-temporo-parietal pattern previously noted only in Alzheimer's disease, and four with large focal deficits. Neither the existence of the abnormal scan nor the particular pattern of abnormality correlated with the results of other diagnostic tests. These preliminary results raise the possibility that SPECT scans may offer an additional valuable diagnostic instrument in CNS lupus, although further studies are necessary to delineate their precise role.

Kenneth McKenzie, Harvey Cushing, and the early neurosurgical treatment of spasmodic torticollis.

In 1923, Dr. Kenneth McKenzie trained at the Peter Bent Brigham Hospital under Dr. Harvey Cushing. At that time, a patient with spasmodic torticollis came to Cushing and was treated with an innovative operation for this disorder with good results. This case sparked an interest in Dr. McKenzie, who published the case 1 year later. In reviewing the surgical histories from the Peter Bent Brigham Hospital, we have found the original records of this well-documented case. The record includes postoperative drawings of the intraoperative field by Dr. Cushing, a sketch by Dr. McKenzie illustrating the postoperative sensory examination, and pre- and postoperative photographs of the patient.

MR imaging of paraneoplastic limbic encephalitis.

Paraneoplastic limbic encephalitis is a rare disorder that has been previously diagnosed on clinical and pathologic grounds without good radiologic correlation. We present the case of a 42-year-old woman who developed gradually progressive limbic dysfunction 4 years after undergoing mastectomy for breast cancer. Although CT scans were normal, magnetic resonance (MR) imaging showed signal abnormalities in the medial portions of both temporal lobes, the amygdaloid nuclei, and the hypothalamus. An MR-guided temporal lobe biopsy confirmed the presence of encephalitis.

Urodynamic assessment of children with cerebral palsy.

More than a third of the children with cerebral palsy present with dysfunctional voiding symptoms. Clinical evaluation and urodynamic study of cerebral palsy patients were performed to characterize the symptoms, to define the type of neurological deficit and to document its effect on voiding dynamics. We evaluated flow rate, and cystometrographic and external sphincter electromyographic findings in 57 children with cerebral palsy. Upper and lower motor neuron lesions were defined by standard criteria. Of the children 86 per cent had evidence of a pure upper motor neuron injury and 11 per cent manifested electromyographic findings suggestive of incomplete lower motor neuron sphincteric injury. The latter deficit could not be predicted on the basis of clinical neurological findings but it was suggested by a history of neonatal cyanosis. Treatment protocols achieved continence in more than 75 per cent of the children. The voiding dynamics in children with cerebral palsy have not been assessed previously. We have defined the lower urinary tract dysfunction in these patients, and provide a rational and effective plan of management.