The effect of adrenalectomy on the circadian variation in the rate of kindled seizure development.

The hypothalamic-pituitary adrenal axis (HPAA) is activated during kindled seizures and the circadian changes in this axis may contribute to the circadian variation in the kindling rate. Changes in the rate of seizure development were examined in rats that were amygdala kindled in the a.m., at midday and in the p.m.. Sham operated control groups were compared to adrenalectomized groups. Adrenalectomy had no effect on the midday rate but abolished the normal circadian variation by accelerating the rate in the a.m. and decreasing the rate in the p.m.. These results suggest a complicated relationship of kindled seizure rate to the hormones of the HPAA axis.

Reassessment of the clinical significance of periodic lateralized epileptiform discharges in pediatric patients.

A review of clinical data from 18 pediatric patients with periodic lateralized epileptiform discharges and bilateral independent periodic lateralized epileptiform discharges (PLEDs and BIPLEDs) showed 2 with chronic neurologic illness, 6 with a history of prior seizures, 14 with depressed sensorium at the time of EEG, 5 deaths, and 8 of 13 survivors with neurologic deficits. These findings are similar to the combined data from reports involving adult patients only. Separating pediatric patients with PLEDs from those with BIPLEDs shows some influence from patients with BIPLEDs. Overall, our data do not suggest significant clinical differences for PLEDs between children and adults.

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.

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.

Neurologic abnormalities in cobalamin deficiency are associated with higher cobalamin "analogue" values than are hematologic abnormalities.

Serum cobalamin "analogue" levels were estimated by the discrepancy in cobalamin results with radioassays done with pure intrinsic factor and R binder in 364 patients with low cobalamin levels. No differences were found among the various causes of low cobalamin levels, except for the lower "analogue" levels among pregnant women. However, 76 patients with low cobalamin levels and primarily neurologic (spinal cord, neuropathic, cerebral, or a combination of these) symptoms had significantly higher "analogue" levels than 19 patients with primarily hematologic abnormalities. Moreover, the "analogue" levels correlated with hemoglobin values and were significantly higher in patients without megaloblastic changes in their bone marrow than in patients with megaloblastosis. An analysis limited to 47 patients with pernicious anemia yielded similar findings. The seven patients with only neurologic abnormalities had higher "analogue" levels than did the nine patients with only hematologic abnormalities. Because of the higher "analogue" levels, the assay done with R binder failed to register low cobalamin levels in 33 of 76 patients with low cobalamin levels and primarily neurologic abnormality (compared with only two of 19 with hematologic abnormality) and in 10 of 20 patients with pernicious anemia who had neurologic abnormalities (compared with only two of 12 without such abnormalities). These differences between patients with hematologic disturbances and patients with neurologic disturbances, and the inverse relationship of "analogue" level with severity of anemia, suggest that the disproportionate accumulation of analogues may explain why some patients with cobalamin deficiency display neurologic abnormalities while others do not.

Unsuspected pernicious anemia in a patient with sickle cell disease receiving routine folate supplementation.

Although the issue of folate supplementation in sickle cell anemia remains controversial, routine supplementation has become common. The major drawback to indiscriminate folate therapy is the potential of masking findings of vitamin B12 (cobalamin) deficiency. This has been dismissed as a problem in sickle cell anemia because of the generally young age of the patients. However, because young blacks, especially women, are at higher risk for developing pernicious anemia than whites, sickle cell anemia and pernicious anemia can be expected to coexist occasionally. In this article we describe such a patient and recommend that routine folate supplementation should not be given in sickle cell anemia before determining the vitamin B12 status.

Short-latency somatosensory evoked potentials correlate with the severity of the neurological deficit and sensory abnormalities following cerebral ischemia.

Short-latency somatosensory evoked potentials (SSEPs) were studied in 49 patients who had suffered hemispheric or thalamic ischemia, including 6 patients with transient ischemic attacks (TIAs) and 3 patients with reversible ischemic neurological deficits (RINDs). SSEPs were abnormal in 30 patients (61%). SSEP abnormalities correlated with the presence of sensory deficit and the degree of neurological deficit. SSEPs were normal following TIA but were abnormal in 2 of 3 patients with RINDs. SSEPs were abnormal in some patients without sensory deficits suggesting that sensory pathways may be affected when clinically inapparent.

Atypical cobalamin deficiency. Subtle biochemical evidence of deficiency is commonly demonstrable in patients without megaloblastic anemia and is often associated with protein-bound cobalamin malabsorption.

We performed studies in 25 patients with low serum cobalamin levels who had few if any clinical or hematologic findings of cobalamin deficiency. All but three had morphologically normoblastic hematopoiesis, and 15 were not even anemic. None of those tested excreted methylmalonic acid or homocystine. Nevertheless, the dUST identified metabolic abnormalities in 18 of the 25 cases. In vitro additives were essential in the dUST. Especially noteworthy was MTHF, whose addition unmasked an otherwise undetectable dUST abnormality in four cases. Why MTHF appears to act as a "stress test" in this setting is unknown but deserves further attention. Seven patients had early forms of classical malabsorptive states such as pernicious anemia, defined by abnormal Schilling test results. Among the rest, seven of 13 patients displayed malabsorption of protein-bound cobalamin despite normal absorption of free cobalamin by the Schilling test. In two patients, initially normal Schilling test results became abnormal the following year. These findings demonstrate that seemingly falsely low serum cobalamin levels often indicate subtle biochemical cobalamin deficiency. Early stages of pernicious anemia or other classical malabsorptive states are sometimes responsible for such subtle deficiency. However, malabsorption confined to protein-bound cobalamin is an equally common cause. Current concepts of cobalamin deficiency and the absorptive defects that can cause it should be expanded to include atypical defects requiring newer methods of identification.

Low serum cobalamin levels in primary degenerative dementia. Do some patients harbor atypical cobalamin deficiency states?

Serum cobalamin (vitamin B12) levels were analyzed retrospectively in 17 patients with primary degenerative dementia and 11 with specific demonstrable causes of dementia (secondary dementia). The prevalence of low cobalamin levels was significantly increased in primary dementia (29% vs 0% in secondary dementia). Because typical findings of deficiency often seemed absent, we prospectively studied two other patients with primary dementia and low cobalamin levels. Neither of these two had megaloblastic anemia; one had a normal Schilling test while the other's was borderline. Despite this absence of the expected findings, the deoxyuridine suppression test gave biochemical evidence of cobalamin deficiency in both cases. Our survey of 28 patients thus established that low serum cobalamin levels are frequent in primary dementia. Our findings in the two prospectively studied cases (as well as in some of the patients in the survey) indicate that these levels are associated in at least some cases with an atypical deficiency state rather than with disorders such as pernicious anemia. Such atypical deficiency states cannot be identified by classic hematological criteria or by the Schilling test.

Physician response to low serum cobalamin levels.

Physician response to a low serum cobalamin result was evaluated in 250 patients. In 42% of cases, no response whatsoever to the low level was found. In 24%, response was suboptimal. In only 34% of cases was management adequate from a diagnostic and therapeutic aspect. Moreover, 13% of all patients were treated with folic acid alone. In addition to the lack of attention to the bulk of cases that had subtle abnormalities or that were not truly cobalamin-deficient, many cases with typical findings of deficiency were ignored. It should also be noted that many truly deficient patients had quite atypical clinical and hematologic features, and the classic picture emphasized in textbooks probably applies mainly to late cases with florid manifestations. These findings raise disturbing questions about the medical management of cobalamin deficiency. They also touch on the more general issue of how physicians view and respond to laboratory abnormalities.

Short-latency somatosensory evoked potentials in myotonic dystrophy: evidence for a conduction disturbance.

Short-latency somatosensory evoked potentials were recorded in 13 patients with myotonic dystrophy (MyD). The MyD were compared with age-matched controls. The mean conduction latency between the brachial plexus and dorsal column nuclei (EP-N14) was significantly longer for the MyD. Results suggest an afferent conduction disturbance in MyD.

Auditory evoked potentials in coma after closed head injury: a clinical-neurophysiologic coma scale for predicting outcome.

We studied auditory evoked potentials in 45 head-injured patients. All but three were comatose or stuporous at the time of study. Preservation of brainstem auditory or long-latency auditory evoked potentials predicted good outcome. The Glasgow coma scale (GCS), the clinical subtotal of the neurophysiologic coma scale (NPCS), and the NPCS had predictive accuracies of 71%, 82%, and 82%. Although there were 22 falsely pessimistic predictions with the GCS and 9% with the clinical subtotal of the NPCS, there were no falsely pessimistic predictions with the NPCS.

The deoxyuridine suppression test identifies subtle cobalamin deficiency in patients without typical megaloblastic anemia.

Four patients had serum cobalamin levels that were initially thought to be falsely low. None of the patients had the typical hematologic and clinical features of cobalamin deficiency and the three so tested had normal cobalamin absorption and/or gastric function. However, the deoxyuridine suppression test result was abnormal in all four cases. The abnormality was improved by adding cobalamin in vitro but, in three of the four cases, was not corrected and, indeed, was made worse by the addition of methyl tetrahydrofolate. These results established metabolically the presence of cobalamin deficiency. The recently improved cobalamin radioassays may be unmasking some atypical and, heretofore, unappreciated cobalamin-deficiency states (only one of our four patients would have come to attention with the older radioassays). These can be identified with the deoxyuridine suppression test, particularly when specific in vitro additives are included.

Triphasic waves: a reassessment of their significance.

Electroencephalograms and case histories of 50 patients with triphasic waves were reviewed. EEGs were studied for slowed dominant activity, anteriorly dominant triphasic waves, anterior-posterior lag time and bursts of triphasic waves. Etiologies of triphasic waves were: hepatic (28), azotemia (10), anoxia (10) and hyperosmolarity (2). Sixteen hepatic and two azotemic patients showed all of these characteristic EEG features. Triphasic waves demonstrating all of these features are highly characteristic of but are not pathognomonic for hepatic encephalopathy. Prognosis correlated best with the type of hepatic injury and deteriorating renal function. We postulate that triphasic waves are generated by the same thalamocortical volleys which normally induce spindles.

Abnormal visual evoked potentials in myotonic dystrophy.

Pattern-shift visual evoked potentials (VEPs) were recorded in 17 patients with myotonic dystrophy. Abnormalities of latency or amplitude were found in 10 patients (59%) with no obvious retinal or other significant ocular abnormality. All patients had a visual acuity of 20/30 or better. Since most patients had bilateral VEP abnormalities, localization of the disturbance was not certain.

EEG monitoring of clinical coma: the compressed spectral array.

Twenty-four comatose patients were studied by 16-hour compressed spectral array (CSA), made from four-channel portable EEG recordings. Causes of coma included head injury (15), anoxia (6), and brainstem strokes (3). CSA was classified on the basis of frequency and alternating or nonalternating patterns. Alternating CSA was significantly associated with survival (p less than 0.005) in the head-injured and anoxic group combined, and in the head-injured subgroup (p less than 0.013). The prognostic value of CSA equaled the Glasgow Coma Scale or neurologic examination and occasionally added prognostic information.

Localizing and prognostic value of auditory evoked responses in coma after closed head injury.

We studied brainstem auditory evoked responses (BAERs) in 26 comatose patients after head injury, and long-latency auditory evoked responses (AERs) in 24 patients. BAERs-AERs were graded for abnormality to evaluate graded outcome. Only six patients had central BAER abnormalities. AERs were abnormal in 21, and all patients with abnormal BAER had abnormal AER, implying that the major site of injury affected the cerebral hemispheres. BAER was abnormal in only 5 of 12 with decerebration, suggesting that decerebration may occur with diffuse hemispheric injury. BAER (p less than 0.01) and AER (p less than 0.01) strongly correlated with outcome. Preservation of AER and normal BAER indicated good quality of survival; absent AER and normal BAER, survival; and absent AER and abnormal BAER, severe disability or death. BAER-AER predicted outcome as accurately as the detailed neurologic examination and occasionally added predictive power.