Familial cerebellar ataxia with muscle coenzyme Q10 deficiency.

OBJECTIVE: To describe a clinical syndrome of cerebellar ataxia associated with muscle coenzyme Q10 (CoQ10) deficiency. BACKGROUND: Muscle CoQ10 deficiency has been reported only in a few patients with a mitochondrial encephalomyopathy characterized by 1) recurrent myoglobinuria; 2) brain involvement (seizures, ataxia, mental retardation), and 3) ragged-red fibers and lipid storage in the muscle biopsy. METHODS: Having found decreased CoQ10 levels in muscle from a patient with unclassified familial cerebellar ataxia, the authors measured CoQ10 in muscle biopsies from other patients in whom cerebellar ataxia could not be attributed to known genetic causes. RESULTS: The authors found muscle CoQ10 deficiency (26 to 35% of normal) in six patients with cerebellar ataxia, pyramidal signs, and seizures. All six patients responded to CoQ10 supplementation; strength increased, ataxia improved, and seizures became less frequent. CONCLUSIONS: Primary CoQ10 deficiency is a potentially important cause of familial ataxia and should be considered in the differential diagnosis of this condition because CoQ10 administration seems to improve the clinical picture.

Hereditary congenital nystagmus and gaze-holding failure: the role of the neural integrator.

Congenital nystagmus (CN) may be due to an instability of the neural integrator responsible for gaze holding. This longitudinal study tests that hypothesis, investigates the saccadic instabilities of relatives, and assesses the effects of afferent stimulation on both the CN and the coexisting gaze-holding failure. We recorded four siblings who had CN and gaze-holding failure while fixating in primary position and lateral gaze. In lateral gaze, the CN waveforms were superimposed on the centripetal drift caused by the gaze-holding failure; the drift time constants ranged from 300 to 1,450 msec. CN waveforms lacked extended foveation periods. Saccadic instabilities were present in the father and two clinically unaffected siblings; the mother's eye movements were normal. We conclude that CN in the subjects of this study, and in others with idiopathic CN, is not due to gaze-holding abnormalities, and we speculate that development of the fixation reflexes that produce CN foveation periods requires some minimal foveation interval during which the target image is in the foveal area with low retinal slip velocity and acceleration.

Very-low-birthweight children and speech and language development.

Very low birthweight (VLBW) is often considered to be a risk factor for speech and language disorders, yet data are equivocal. The present study compared speech and language comprehension and production between 249 very-low-birthweight (VLBW: less than 1.5 kg) and 363 normal-birthweight 8-year-olds, randomly sampled in a geographic area. Mean performance for the entire group of VLBW children and for the group when 24 VLBW children with major neurologic abnormalities were excluded, was significantly lower than for controls on the majority of speech and language measures. Further analyses addressed the clinical significance of these statistically significant differences. Test scores were converted to standard scores and grouped according to standard deviation intervals, thus portraying each child's performance in terms of the magnitude of discrepancy from each test's mean. When the 24 children with major neurological abnormalities were excluded, no significant differences between the VLBW and control children were observed. Using discrepancy between WISC-R performance IQ and language to define specific language impairment (SLI), a higher percentage of control than VLBW children were identified as having SLI. Neonatal risk factors did not differentiate between VLBW children with or without SLI. A higher proportion of VLBW than control children did present subnormal language associated with IQ less than 85, hearing deficits, and/or major neurological impairments. Thus, SLI is not more common among VLBW than control children. Language deficits accompanied by more general developmental problems, however, are more frequent.

Enamel defects: a developmental marker for hemifacial microsomia.

We have observed primary tooth enamel defects in 4 children with hemifacial microsomia. The distribution of enamel defects was concordant with the laterality of craniofacial anomalies in these patients and was most pronounced on the maxillary incisors. Since the location of enamel defects serves as a chronicle for the events of tooth formation, we propose that enamel defects may serve as a developmental marker for the events leading to hemifacial microsomia.

Pontine myelinolysis and delayed encephalopathy following the rapid correction of acute hyponatremia.

We describe a case of pontine myelinolysis associated with hyponatremia and hyperammonemia resulting from bladder irrigation during a transurethral prostatic resection. Following the procedure the patient exhibited seizurelike activity. He underwent rapid correction of the hyponatremia, he initially recovered but developed encephalopathy 19 days later. Magnetic resonance images showed symmetrical lesions in the white matter of the cerebellar peduncles. A relatively small pontine lesion was also noted. The patient later recovered. This case demonstrates that myelinolysis associated with rapid correction of hyponatremia may be greater in the cerebellar peduncles than in the central pons.

Effect of eyelid closure and vocalization upon the vestibulo-ocular reflex during rotational testing.

During rotational testing of the vestibulo-ocular reflex (VOR), eyelid closure is known to reduce both VOR gain and nystagmus frequency. We tested the effect of vocalization, such as counting aloud, on the VOR in ten healthy normal subjects. Velocity-step and sinusoidal stimuli were applied in complete darkness under three test conditions: 1) eyes open, performing mental arithmetic; 2) eyes closed, performing mental arithmetic; and 3) eyes closed and vocalizing. With velocity-step stimuli, eyelid closure significantly reduced VOR gain (peak eye velocity/head velocity) and nystagmus duration, but vocalization reversed these effects and resulted in the highest gain values. Similar results were obtained for VOR gain during sinusoidal stimulation. This study demonstrates that when eyelid closure is necessary or unavoidable during VOR testing, continuous vocalization ensures responses that are comparable to or better than those with eyes open in darkness.

Maturation of the vestibulo-ocular reflex in normal infants during the first 2 months of life.

We measured the dynamic properties of the vestibulo-ocular reflex (VOR) in 20 healthy, newborn babies, using sinusoidal and velocity-step rotational stimuli. With sinusoidal stimuli, quick phases of nystagmus were uncommon and there was a large phase lead of eye position over head position that exceeded 20 degrees at frequencies below 0.5 Hz. With velocity-step stimuli, primary nystagmus lasted for a mean duration of 10 seconds and was followed by an early reversal phase of nystagmus. By 2 months of age, primary nystagmus induced by velocity-step stimuli was more prolonged (mean duration, 15 seconds) and the reversal phase occurred later. We postulate that these changes reflect maturation of visual pathways essential in calibrating the VOR so that vision remains clear during head perturbations.

Serial MR studies in Menkes disease.

We describe a characteristic combination of findings in a patient with Menkes disease who was serially imaged with magnetic resonance over 2 months. Abnormal intracranial vessels were demonstrated as was the progression of white matter disease.

Hearing and neurologic impairment: insult timing indicated by primary tooth enamel defects.

The association between hearing loss, neurologic impairment, and primary tooth enamel defects was examined in a group of 88 children presenting for hearing evaluation at a tertiary care children's hospital. Forty-one had classifiable enamel defects, reflecting the time and duration of prenatal or perinatal insult. Hearing loss was more prevalent and severe in 19 children with enamel defects of the incisal tooth edge (mean = 61 dB) reflecting a systemic insult at 14 to 16 weeks gestation, than in 7 children with cervical third tooth defects (mean = 23 dB) reflecting insult near term (X2 = 4.08; p less than 0.05). Audiometric findings among the 15 children with incisor defects of the middle third varied; 7 had significant hearing loss and 8 were normal. A correlation was observed between severity of hearing loss (in dB) and estimated time of systemic insult (in weeks gestational age) determined by tooth defect site (r = -0.48; p less than 0.01). The neurologic data revealed similar trends. The group with early systemic insults more frequently had moderate or severe neurologic deficits known to originate early in fetal development. The two groups with third trimester or term insults tended to have mild or no neurologic impairment. A differential susceptibility for developing auditory and neurologic structures based on insult timing is supported.

Spasmus nutans. A quantitative prospective study.

Spasmus nutans includes ocular oscillations, head nodding, and anomalous head positions. No quantitative longitudinal study verifying the natural history of this self-limited condition has appeared in the literature. Using infrared oculography, we prospectively examined the eye movements of otherwise neurologically normal infants in whom a diagnosis of spasmus nutans had been made. At this writing the ocular oscillations and head movements in two of the children were clinically absent, thereby confirming the diagnosis. The ocular movements are characterized by a phase difference between the oscillations of each eye that varies both during one recording session and during development. The dissociated, pendular nystagmus consists of high-frequency oscillations that may be disconjugate, conjugate, or purely uniocular.

Neurologic sequelae of cardiac catheterization.

Neurologic complications are a known and at times tragic consequence of cardiac catheterization. During a four-year period, 1,362 procedures were performed at our institution on children less than 15 years of age. Eighteen children, without prior nervous system disease, developed neurologic sequelae within 24 hours of cardiac catheterization (1.3%). Three presented with seizures only, ten with neurologic deficits, and five with both focal seizures and stroke. Computerized tomography scans (16 patients) demonstrated areas of nonhemorrhagic infarction in all but one. The 18 patients were studied retrospectively for possible factors contributing to the neurologic complications. They were matched to controls by age, cardiac lesion, and catheterization technique. Data examined included catheterization duration and approach, contrast agent, precatheterization urine specific gravity, pre- and postcatheterization hematocrit, blood loss, and intracatheterization events. Catheter and catheter sheath clots were noted in both patient groups. The neurologic complication group had 7/18 intracatheterization neurologic events versus only one in the controls and the change in hematocrit was greater in the complication group (t = 2.89, p less than 0.01). Due to this study's results and to prevent possible thromboembolic events, a heparinization protocol was instituted and patients were prospectively observed for neurologic complications. No neurologic complications have occurred over three years since the institution of this protocol.