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Cobalamin levels are frequently low in patients with dementia, but it is unclear if they represent definable deficiency and what the mechanisms are. Therefore, patients being evaluated for dementia who had low cobalamin levels but no obvious evidence of deficiency were studied hematologically, neurologically and with metabolic tests and were re-evaluated after cobalamin treatment. Abnormalities suggestive of or diagnostic for deficiency were documented in most of the 16 demented and nondemented patients. Metabolic results: 50% of patients tested had abnormal deoxyuridine suppression and 44% had increased serum methylmalonic acid and/or homocysteine levels; these test results correlated with each other. Neurologic results: 73% of patients had clinical abnormalities, primarily mild neuropathies, not attributable to other causes, 75% had electroencephalographic abnormalities, 77% had abnormal visual evoked potentials and 33% had abnormal somatosensory potentials. Metabolic and neurologic dysfunction were present together or absent together in all but 2 cases. Cobalamin therapy improved 50–100% of the various types of abnormalities, although it did not improve cognitive function in the 13 demented patients. Food-cobalamin malabsorption was found in 60% of the patients. Despite the absence of megaloblastic anemia and rarity of traditional malabsorption of free cobalamin, low cobalamin levels in demented patients frequently represent mild cobalamin deficiency and are often associated with food-cobalamin malabsorption. Perhaps most importantly, this is accompanied not only by metabolic changes but by evidence of mild neurologic dysfunction. Their frequent reversibility by cobalamin confirms that these defects indeed arise from cobalamin deficiency. Although the long-standing dementia does not improve, treating such patients with cobalamin has other concrete benefits.

Neuron-specific enolase (NSE) is a sensitive marker of brain injury after stroke, global ischemia, and coma. We report changes in serum NSE (s-NSE) in 19 patients who sustained status epilepticus. s-NSE peaked within 24 to 48 hours after status epilepticus. The mean peak s-NSE level for the entire group was elevated compared with the levels for normal controls (24.87 ng/ml versus 5.36 ng/ml, p = 0.0001) and for epileptic controls (24.87 ng/ml versus 4.61 ng/ml, p = 0.0001). The mean peak s-NSE level for the 11 subjects without an acute neurologic insult (15.44 ng/ml) was also significantly increased compared with levels for normal and epileptic controls. Further, s-NSE was significantly correlated with outcome and duration. We conclude that s-NSE is a promising in vivo marker of brain injury in status epilepticus and warrants further study in larger populations.

In classic galactosemia, long-term neurologic sequelae can include low cognitive functioning and a curious neurologic syndrome with tremors, dysmetria, and ataxia. An abnormal white-matter signal on cerebral magnetic resonance imaging (MRI) is present in almost all patients; some have mild cerebral or cerebellar atrophy and focal white-matter lesions. The present study was undertaken to assess the integrity of myelinated pathways by recording somatosensory evoked potentials. Results were correlated with age at diagnosis, severity of illness, age at evoked potentials, neurologic examination, MRI studies and cognitive outcome as measured by the Woodcock-Johnson Revised Standard Cognitive Battery. Evoked potentials were abnormal in 17 (28%) of 60 patients who had median nerve, and 26 (77%) of 34 patients who had posterior tibial nerve studies. Abnormalities of the central rather than the peripheral nervous system were most common. Evoked potentials correlated with severity of presenting symptoms (P = .011), age at evoked potential testing (P = .029), and presence of focal white-matter lesions on MRI (P = .049). Results of neurophysiologic testing showed no correlation with the Woodcock-Johnson Battery. Patients with classic galactosemia may have abnormal conduction along myelinated pathways that is associated with other central deficits. Myelin, which contains galactose, may be adversely affected in this inborn error of metabolism. (J Child Neurol 1995;10:32-36).

The P300 is a cognitive event-related potential partially generated by the amygdala/hippocampus complex, the most common source of temporal lobe epilepsy (TLE). In order to test the hypothesis that scalp P300 amplitude is reduced ipsilateral to the epileptogenic focus in TLE, we performed a prospective study of 15 subjects with TLE and compared the lateralizing ability of scalp P300 to interictal EEG. P300 asymmetries in TLE were compared with asymmetries in a control group. P300 amplitude was significantly attenuated ipsilateral to the epileptic focus. P300 amplitude reduction correctly lateralized the focus in 82% of the cases ( p = 0.02). We conclude that scalp P300 accurately lateralizes the epileptogenic focus in TLE. Further studies are needed to define the potential role of P300 in the presurgical evaluation of TLE.

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.

✓ Twenty-one patients operated on for unruptured intracranial aneurysms were studied retrospectively in order to identify the incidence of postoperative seizures, factors predictive of seizures, and the response to discontinuation of antiepileptic drugs. The overall risk of postoperative seizures in initially seizure-free patients was 15.7%. Although seizures were not uncommon, antiepileptic drugs were successfully tapered in most of the patients before 12 months.

Objectives: To determine the relative magnitudes of neuron-specific enolase (NSE) levels after complex partial status epilepticus (SE), absence SE, generalized convulsive SE, and subclinical generalized convulsive SE (frequently referred to as acute symptomatic myoclonic status epilepticus).Background: NSE is a marker of acute brain injury and blood–brain barrier dysfunction, which is elevated in SE.Methods: Serum NSE levels were drawn in 31 patients 1, 2, 3, and 7 days after SE. Patients were classified as acute symptomatic or remote symptomatic, and the duration and outcome of SE were determined and correlated with the peak NSE level.Results: NSE was elevated significantly in all four subtypes of SE, but NSE levels were highest in complex partial and subclinical SE. The mean peak NSE level for the complex partial SE group was 23.88 ng/mL (n = 12), 21.5 ng/mL for absence SE (n = 1), 14.10 ng/mL for the generalized convulsive SE group (n = 12), and 37.83 ng/mL for the subclinical SE group (n = 6), all of which was significantly higher than normal control subjects (5.02 ng/mL). Outcome was significantly different between the three groups (p = 0.0007), and was significantly worse for subclinical SE (p = 0.0005, subclinical versus generalized convulsive SE).Conclusion: Serum NSE levels were highest in complex partial and subclinical generalized convulsive SE. The extremely high levels of NSE in subclinical SE reflect the severity of the acute neurologic insults and poor outcome common to subclinical SE. High NSE levels in complex partial SE reflects the long duration of SE in this subgroup, and potential for brain injury.

Low serum cobalamin levels are common in conditions such as dementia and often represent mild deficiency. We surveyed serum cobalamin levels prospectively in spouses and blood relatives of demented patients to determine if any familial predisposition exists for the low levels. Cobalamin status in most of the relatives found to have low levels was assessed further by means of blood counts, metabolic tests, neurologic evaluation, absorption studies and response to cobalamin therapy. Serum cobalamin levels in 36 spouses correlated with those of the 36 demented patients related to them (r = 0.46, p = 0.004). A significant association was not seen in 34 blood relatives of 34 demented patients (r = 0.27). Most importantly, 67% of the spouses of demented patients with low serum cobalamin had low values themselves, compared with only 3% of the spouses of patients with normal levels (p = 0.001). Detailed study of 4 of the 5 spouses (and 3 blood relatives) with low cobalamin levels showed no anemia in any case. Nevertheless, 4 of the subjects had metabolic evidence of deficiency and one had electrophysiological abnormalities; all these defects improved with cobalamin therapy. These observations identify a hitherto unsuspected group of people at high risk for cobalamin deficiency and suggest that spouses of demented patients with low cobalamin levels should also have their cobalamin levels measured. The increased frequency of low serum cobalamin levels in spouses of demented patients with low levels represents in most cases a true, mild cobalamin deficiency that responds to treatment.

Summary: Purpose: To determine whether complex partial status epilepticus (CPSE) causes brain injury in humans. Serum neuron-specific enolase (s-NSE) is an accepted marker of acute brain injury, and increases in s-NSE have been correlated with the duration and outcome of generalized convulsive status epilepticus. s-NSE levels in CPSE are unknown. Increase in s-NSE in CPSE would provide new information about the degree of brain injury in CPSE and would help confirm that CPSE is a medical emergency. Methods: This was a pilot prospective study of serial levels of s-NSE and outcome in CPSE. Eight patients with confirmed CPSE and no acute neurologic deficit were identified prospectively. Results were compared with those of normal and epileptic control groups, and outcome was assessed at hospital discharge or at 7 days with the Glasgow Oucome Scale (GOS). Results: The mean peak s-NSE was 21.81 ng/ml, which for the 8 patients with CPSE was four times higher than that of normal controls (mean s-NSE = 5.36 SD = 1.66, p = 0.0003) and epileptic controls (mean s-NSE = 4.61 SD = 1.74, p. = 0.001). Conclusion: The increase in s-NSE provides new evidence that CPSE causes brain injury in humans.

A pilot case-control quantitative study of the hippocampus in patients with severe status epilepticus was performed to identify specific patterns of pyramidal cell loss. Pyramidal cell densities from five patients who died following status epilepticus were compared with five normal controls and five controls matched for age, hypoxia/ischemia, previous epilepsy, and alcohol abuse. Neuronal densities were greatest in the normal control group and least in patients with status epilepticus. Significant reductions were identified in Sommer's sector (prosubiculum and CA1) as well as in CA3 when compared to normal controls.

Auditory event-related potentials (ERPs) were performed in 20 patients with nontraumatic coma to determine the presence of a P300 ERP in coma and its association with the Glasgow Coma Score and awakening (Glasgow Outcome Score,or = 3). A standard "oddball" paradigm was used: frequent tone, 1 kHz; rare tone, 2 kHz and 4 Hz; probability, 20%. The Glasgow Coma Score was determined concurrently with the P300 ERP. Thirty percent (6/20) of the comatose patients had a P300 ERP. The mean Glasgow Coma Score was significantly higher for those with a P300 ERP. Eighty-three percent (5/6) of those with a P300 ERP awoke. Presence of a P300 ERP was associated significantly with awakening, but absence of a P300 ERP did not preclude it.

Reply from the Authors: We welcome the comments of Schmitt and Bandtlow. In review, we reported the first prospective study of serum neuron-specific enolase (s-NSE), a marker of acute neuronal injury after stroke and anoxia, in status epilepticus (SE). Our specific aim was to determine if s-NSE is elevated after SE, and if so, was it correlated with outcome and duration. The results of this pilot study were highly significant. s-NSE was elevated even in those without an acute neurologic insult (remote symptomatic SE). Further, for the 19 patients s-NSE was highly correlated with the 1-week Glasgow Outcome Score (GOS) and the duration of SE. Schmitt and Bandtlow assert that CSF NSE is the more promising marker of brain injury, and cite their own unpublished data. They suggest that s-NSE is more variable than CSF NSE, but multiple studies in animals and humans have shown s-NSE to be a highly specific marker in stroke and anoxic-coma. [2-4] Roine et al. [3] have pointed out "... the relatively high specificity of the serum test and the good correlation between serum and CSF levels of NSE suggest that it may be useful as a routinely available substitute for CSF measurements.'' We have collected CSF and serum samples in 10 patients in SE, and found CSF NSE to be …

A subject is described who can voluntarily select and hold either of two qualitatively different states of consciousness. Evidence is presented which confirmed differential left or right hemisphere dominance in each state. Asymmetries of EEG alpha and task performance scores indicated a state-dependent shift in functional lateralization. Evoked response studies showed directional changes in rate of interhemispheric transmission correlated with state-related hemisphere dominance. These findings demonstrated the capability for voluntary endogenous control of cerebral dominance under natural conditions.

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.

A group of 11 patients with a variety of lesions affecting the 3rd ventricle have been treated using a direct transcallosal interfornicial approach to the region. In 3 patients, no attendant hydrocephalus was present. In an effort to minimize potential cortical injury related to the approach, we studied the venous anatomy in the region of the coronal suture. Based on this study, appropriate flap placement and interhemispheric entry points were defined. Although no lasting, clinically apparent morbidity was observed in any of the 11 cases, we performed more sophisticated studies of the interhemispheric transfer of somesthetic and perceptual motor tasks, as well as psychometric testing related to parameters of intelligence and memory, 3 to 8 months postoperatively in 6 cases. The results and clinical material indicate that this surgical technique is a safe, feasible alternative in the management of a wide spectrum of pathological lesions within this region. A transcallosal, interfornicial approach offers excellent visualization of the entire 3rd ventricle without the dependence on hydrocephalus or an extensive extra-axial mass to enhance the exposure. With proper planning and technique. it may be accomplished with a minimum of physiological consequence.

Brain-stem (BAEP) and middle-latency (MLAEP) auditory evoked potentials were recorded in zero noise and in 3 levels of continuous ipsilateral broadband noise. New information is presented on the efefcts of noise on BAEP wave I. Latency of wave I was not changed by increasing noise, but wave V latency linearly increased. Amplitude of waves I and V decreased non-linearly. The amplitude decrease was equivalent for both waves and occured only at the higher noise levels. The dissociation of latency effcets fior waves I and V indicates a central component for the effect of noise on latency. The parallel amplitude change for waves I and V suggests a largely peripheral component.. The MLAEP Pa latency also increased with increasing noise further supporting a central mechanism.

Evoked responses can be characterized with respect to latency and amplitude. The latency of the evoked response depends upon whether the person is right-handed or left-handed. In right-handed subjects, the left (dominant) hemisphere has a longer latency than the right when used as a direct hemisphere. Similarly, when the so-called dominant (right) hemisphere of left-handed subjects is used as the direct hemisphere it shows a longer latency than when the non-dominant hemisphere is used. This has been interpreted as an indication that a longer processing time is required in cortical or subcortical systems. Another asymmetry in response occurs with respect to amplitude. While right-handed persons show no difference in the amplitude of the response between right (direct) and left (direct) hemispheres, this is not so for left-handed individuals in whom the response of the right (so-called dominant) hemisphere is larger when used as the direct hemisphere. The responses from left- and right-handed people were compared to one another. The left (dominant) hemisphere of right-handed persons has a longer latency than the left (non-dominant) hemisphere of the left-handed person. Similarly, the latency of the responses from the right (dominant) hemisphere of the left-handed subjects is longer than that from the right (non-dominant) hemisphere of right-handed subjects. The amplitude of responses recorded from the right (dominant) hemisphere of left-handed people appears to be larger in general than those from the right (non-dominant) hemisphere of right-handed people, but the data were not statistically significant.

Interhemispheric transmission time (ITT) was derived from vibratory somatosensory evoked potentials (VSEP) arising in homologous cortical sensory--association areas of normals. Two different vibratory sources, an audiometer bone oscillator or an Optacon, were used to stimulate each index finger independently. ITT was calculated by subtracting the latency of the first major peak over the contralateral cortex (CL) from the latency of the corresponding peak over the ipsilateral area (IL-CL = ITT). Readily identified aberrant values were observed and rejected from the series of measurements leaving clear normal ranges. In addition to providing normal ITT data, clinical correlations were illustrated in two different disorders. Results suggested that important information relating to diagnosis and therapy of brain pathologies affecting interhemispheric transmission can now be made available in both experimental and clinical situations.

Studies of patients who have undergone surgical section of the forebrain commissures indicate that the two hemispheres are specialized for different cognitive functions. The left hemisphere has been described as superior in speech, calculation, and related linguistic or analytic activities, while the right hemisphere is superior in configurational, spatial, and synthetic activities (SPERRY and GAZZANIGA, 1967; SPERRY, et al., 1969).

Two patients with radiologically confirmed total agenesis of the corpus callosum, and free of gross focal hemispheric pathology, received a battery of lateralized and free-field language and perceptual-motor tests. These tasks allowed a comparison of (1) agenic findings with previous results from surgical commissurotomy patients, and (2) the inter- and intrahemispheric performance for each agenic subject. In general, the results indicate that the two agenic patients do not demonstrate the marked deficits of cross-integration reported after commissurotomy. However, there was an upper limit to their integrative capacity for visual, and to an even greater extent, for fine motor and kinesthetically mediated performance. The tasks that proved particularly difficult appeared to have common factors which may be related to functional capabilities of the ipsilateral motor pathways and anterior commissure.

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.

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.

Summary Cognitive abilities were investigated in three patients with hemispherectomy for noninfantile disease. Two had the right and one had the left hemisphere removed. Results indicate that after right hemispherectomy in the mature brain the left hemisphere remains decidedly more proficient in verbal than nonverbal functions. In the developing younger brain, however, regardless of which hemisphere was removed, less difference exists between abilities in verbal and nonverbal functions, and level of performance is in general lower than in the adult case. Memory functions were impaired after hemispherectomy with removal of the left hemisphere producing the greater deficit.

Norepinephrine has been shown to improve signal-to-noise ratios of sensory systems, including that of the auditory system. Yohimbine has been observed to cause a selective increase of cerebral norepinephrine. It was administered in one dose to sensorineurally impaired subjects with the object of improving their speech hearing in noise. Speech intelligibility was measured by the adaptive procedure. Mild, significant improvement was noted in one of the hearing components, "attenuation," and an adverse effect was shown on "distortion," owing to noise. Auditory brainstem response was improved significantly. The objective of temporarily improving intelligibility in noise was not attained.

A 6-year follow-up of patients harboring microprolactinomas suggests that few patients (3 of 27) demonstrate significant growth of their tumor during this time. The major hazard for such patients who are not treated seems to be their risk for the development of premature osteoporosis in the face of sustained hyperprolactinemia. The risks of this complication may exceed the risks of early surgical intervention in selected patients. This short term risk of tumor growth (about 10%) must be weighed in the decision about therapeutic endeavors.