Imaging Acetaldehyde Formation During Ethanol Metabolism in Living Cells using a Hydrazinyl Naphthalimide Fluorescent Probe.

The metabolism of ethanol to acetaldehyde has been visualized in living lung epithelial cells using a hydrazinyl naphthalimide fluorescent probe. Utilizing a condensation reaction between carbonyls and a hydrazine moeity, we demonstrate that the fluorescent probe (Aldehydefluor-1) AF1 reacts with a range of reactive carbonyl species including formaldehyde, acetaldehyde, glyoxylic acid, and methyl glyoxal. With AF1, it is possible to directly visualize endogenous carbonyl metabolites. Here, we have applied it towards the visualization of acetaldehyde generated from alcohol dehydrogenase mediated ethanol metabolism, validating it as a useful tool to study the roles of alcohol in respiratory disease and other pathological mechanisms.

Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure.

This report provides the first detailed neuropathological study of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in humans. All 3 subjects self-administered the drug under the impression it was "synthetic heroin" and subsequently developed severe and unremitting parkinsonism, which was L-dopa responsive, at least in the earlier stages of illness. Survival times ranged from 3 to 16 years. Neuropathological examination revealed moderate to severe depletion of pigmented nerve cells in the substantia nigra in each case. Lewy bodies were not present. In Patients 1 and 2, there was gliosis and clustering of microglia around nerve cells. Patient 3 had a similar picture and also showed large amounts of extraneuronal melanin. These findings are indicative of active, ongoing nerve cell loss, suggesting that a time-limited insult to the nigrostriatal system can set in motion a self-perpetuating process of neurodegeneration. Although the mechanism by which this occurs is far from clear, the precedent set by the cases could have broad implications for human neurodegenerative disease.

Long-term seizure outcome following corpus callosotomy in children.

INTRODUCTION: The long-term outcome of pediatric patients undergoing corpus callosotomy (CC) for palliative control of medically intractable seizures is presented. METHODS: During a 27-year period, 43 patients, 20 years of age or younger, underwent CC for seizure palliation and had a minimum of 1 year follow-up. Seizure reduction and stability of that outcome for individual seizure types and for most disabling seizure were reviewed. RESULTS: Overall, 63% of the seizures documented showed a good response. For the most disabling seizure, 56% of the patients had good outcomes. Changes in outcome status occurred within the first 6 months, and outcome was largely maintained after that point. CONCLUSION: Callosotomy achieves the goal of seizure palliation in more than half of the patients, with stable, good outcomes being maintained in the majority of patients.

Pure alexia: clinical-pathologic evidence for a lateralized visual language association cortex.

Traditional views of pure alexia have held that the disorder results from a disconnection between the secondary visual cortices of both hemispheres and the angular gyrus of the dominant hemisphere. Evidence has accumulated, however, suggesting the importance of the posterior inferior temporal area in visual language processing. We describe clinical-pathological support for the presence of a lateralized visual language association area residing in the dominant posterior inferior temporal lobe.

Isolation of a right hemisphere cognitive system in a patient with anarchic (alien) hand sign.

We report evidence of isolated conceptual knowledge in the right hemisphere of a woman with chronic anarchic hand sign after ischemic infarction of the central four-fifths of the corpus callosum. Limited visual information was available to the right hemisphere, access to medial temporal structures subserving memory was disrupted and disconnection from left hemisphere language structures was complete. Still, the right hemisphere could build mental representations of objects via tactile input and use them in cross-modal matching. These representations were not accessed consistently in auditory comprehension or naming tasks. This functional specificity and its pathoanatomical correlates demonstrate that the study of anarchic hand sign can illuminate not just motor control issues but may inform our understanding of the representation and lateralization of conceptual knowledge as well.

Parkinson's and Alzheimer's: new tools, new attitudes in patient care.

In 1946, the differential diagnosis of cognitive failure resided in the hands of psychiatrists. Not until the late 1960s was permanent doubt cast on the arteriosclerotic origins of dementia. Neuro-diagnostic studies 50 years ago were limited to skull x-rays. Many neurologic signs that would now be considered indicative of Parkinson's disease (PD) were thought in 1946 to typify old age. The diagnosis of PD was made on clinical grounds, and in that regard little has changed. For treatment of PD, textbooks then had little to offer, compared with the wide range of drug therapies available today. Unknown in the mid-1940s, the molecular biology of DNA now allows practitioners a glimpse at the highly complex and multifactorial origins of Alzheimer's disease.

Alexia without agraphia associated with spleniogeniculate infarction.

Pure alexia, following an infarction in the distribution of the left posterior cerebral artery, is attributed to damage of the left occipital lobe and the splenium of the corpus callosum. We describe a case of pure alexia in a 57-year-old woman with infarction of the left lateral geniculate body and the splenium of the corpus callosum, a variation on this classic disconnection syndrome.

Corpus callosotomy for intractable seizures in the pediatric age group.

The results of corpus callosotomy in 18 patients 16 years old and younger are presented. Eighty-three percent of our patients have had a significant improvement from the surgery (a decrease in seizure frequency of greater than 80% or no longer having generalized atonic, tonic, or tonic-clonic seizures). The procedure seems to be well tolerated in young patients, and we have not noted a postoperative deterioration in behavior, memory, or language function in our patients. One of our patients died in status epilepticus 3 months after surgery. Nevertheless, we have not encountered any serious morbidity in our other patients. Corpus callosotomy can be considered for children with intractable seizures, especially when generalized atonic, tonic, or tonic-clonic (whether primary or secondary) seizures are the major seizure type.

Central corpectomy for cervical spondylotic myelopathy: a consecutive series with long-term follow-up evaluation.

Since 1984, a consecutive series of patients with cervical spondylotic myelopathy has been treated by central corpectomy and strut grafting. This report focuses on 40 cases operated on between 1984 and 1987 and followed from 2 to 5 years. The perioperative complication rate was 47.5%, with a 7.5% incidence of persistent sequelae: severe C-5 radiculopathy in one patient, swallowing dysfunction in one, and hypoglossal nerve palsy in one. No single factor (age, duration of symptoms, or severity of myelopathy) was absolutely predictive of outcome; however, syndromes of short duration had the best likelihood of cure. Similar outcomes were associated, individually, with long duration of symptoms, age over 70 years, and severe myelopathy. After factoring a 5% regression of improvement, the long-term cure rate was 57.5% and the failure rate was 15%. Myelopathy worsening was not documented.

Asymmetries of the auditory areas of the cerebrum.

A total of 29 human cadaver brains were examined for asymmetries of the left and right Sylvian fissure, Heschl's gyri, and planum temporale. The mean lengths of these structures were all significantly greater on the left side than on the right. There was considerable morphologic variability in these structures as evidenced by the number of Heschl's gyri that ranged from one to three per hemisphere in different brains, although there was no significant asymmetry in the number of Heschl's gyri in individual brains. Asymmetry of the Sylvian fissure was correlated with the greater length of the planum temporale on the left side. Although it is well known that the planum temporale is larger in the left hemisphere than in the right, little has been reported on Heschl's gyri in this regard. It is possible that asymmetries in higher auditory and language function may be attributable to anatomic asymmetries of not only the planum temporale but also Heschl's gyri.

Transient partial oculomotor nerve paresis with posterior communicating artery aneurysm. A case report.

A 38-year-old woman is described who developed a partial right oculomotor paresis which cleared spontaneously prior to clipping of an associated nonhemorrhagic bilobate right anterior communicating artery aneurysm.

Electrophysiologic and behavioral auditory findings in multiple sclerosis.

An auditory test battery composed of seven behavioral and electrophysiologic measures, in addition to pure tone testing, was administered to 33 subjects with definite multiple sclerosis. More than 40% of the subjects with normal peripheral hearing presented with subjective complaints of hearing difficulties. Auditory brainstem response (ABR) was found to be the most sensitive individual test in detecting central auditory dysfunction. Further analyses suggested that the combination of ABR and masking level difference (MLD) tests was essentially as effective as the entire test battery in detecting dysfunction in these subjects. Dichotic speech measures, unlike other tests, showed a definite laterality effect with the left ear consistently poorer, possibly reflecting interhemispheric involvement.

Magnetic resonance imaging and the "one-and-a-half" syndrome: a case report.

A patient is described who had magnetic resonance imaging (MRI) findings of a left paramedian pontine ischemic stroke. It was associated with right motor sensory and left cerebellar dysfunction and the "one-and-a-half" syndrome of Fisher.

Effect of commissurotomy on complex partial epilepsy in patients without a resectable seizure focus.

Twenty-five patients in a series of 51 undergoing partial or complete section of the corpus callosum for the treatment of intractable epilepsy experienced complex partial seizures among their seizure types preoperatively. Ten of these 25 patients have experienced no further complex partial seizures. Reduction in severity of seizures has been found in 11 of the 15 patients still experiencing this seizure type, and 3 have had greater than 80% frequency reduction. These findings are consistent with the electrophysiologic observations of Lieb on the relative unimportance of the hippocampal commissure in man and the behavioral observations of Quesney on unilateral versus bilateral temporal lobe seizure activity.

Central auditory function following anterior sectioning of the corpus callosum.

This paper describes auditory findings for eight patients with anterior sections of the corpus callosum. Peripheral (pure tone and speech recognition) and five central auditory tests were administered to each of the eight patients prior to surgery and then again approximately 2 weeks after surgery. The central tests administered included a low-pass filtered speech test, the frequency patterns perception test, and three dichotic speech tests. Mean scores for the peripheral tests fell grossly within the normal range preoperatively and showed little change postoperatively. Similarly, scores on the central tests, though somewhat more variable, did not show any obvious differences upon pre- and postsurgical comparison. A comparison of these results with those reported previously for patients with complete commissurotomies (Musiek, Kibbe, and Baran. Semin Hear 1984;5:219-29) revealed that as a group, patients with anterior sections of the corpus callosum showed fewer postsurgery deficits than did the subjects with complete commissurotomies. The lack of an apparent auditory effect in the anterior group is believed to have an anatomical basis.

Neurologic signs in senescence.

We examined 2,029 volunteers 50 to 93 years of age in a cross-sectional study of nine bedside neurologic tests to determine the frequency of "abnormal" responses in uncomplicated aging (senescence). Rates of abnormal responses remained constant until age 70 years, after which they increased significantly. The number of abnormal signs per subject also increased, especially over 70 years of age. These results provide normative data against which these signs may be compared when applied as a clinical screening battery for diffuse cerebral dysfunction.