Biomedical subjects
Publications and source records attributed to J R Hotson.
Dementia was the presenting symptom in a patient with increased serum viscosity secondary to multiple myeloma. Plasmapheresis led to complete resolution of the neurologic syndrome. Serum hyperviscosity should be added to the growing list of reversible causes of dementia. When hyperviscosity-associated dementia is suspected, both serum and whole blood viscosity determinations are indicated.
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Human subjects normally have miniature eye movements during tasks that require steady visual fixation. These eye movements were compared in 12 control subjects and 4 patients with degenerative cerebellar disorders. Slow drifts, small fixation saccades, square waves, saccadic oscillations, flutter, and vertical nystagmus occurred in both control subjects and patients. In the patients, however, fixation eye movements were enlarged and square waves and saccadic oscillations were more frequent. It appears that some forms of pathologic fixation instability are due to defective cerebellar control of fixation eye movements, and that precise measurements of these eye movements may quantitate disorders of cerebellar function.
Both barium (Ba++) and penicillin produce spontaneous epileptiform burst generation in hippocampal neurons in vitro. Recent investigations suggest that Ba++ acts by both adding to a calcium (Ca++)-mediated depolarization and reducing potassium (K+) conductance. In contrast, it has been proposed that penicillin produces burst generation by attenuating inhibitory postsynaptic potentials. However, some evidence suggests that penicillin may also directly alter intrinsic membrane properties. We therefore compared the actions of penicillin and Ba++ on three intrinsic Ca++- or K+-mediated membrane events, namely, CA++ spikes, Ca++-dependent anomalous rectification, and K+-dependent afterhyperpolarization. Ba++ augmented the Ca++ potentials and attenuated the K+-dependent afterhyperpolarization; penicillin had no demonstrable effect on these events. Ba++ produced rhythmical burst firing and oscillations of the membrane potentials, while penicillin caused sporadic burst generation followed by a longlasting afterhyperpolarization. Synchronized, orthodromically evoked burst firing occurred after exposure to penicillin but not to Ba++. Ba++ and penicillin are prototypes of agents which induce epileptogenesis in mammalian cortical neurons by two different but probably interrelated mechanisms. Ba++ causes burst generation by disrupting a delicate balance between depolarizing Ca++ potentials and repolarizing, hyperpolarizing K+ potentials. Penicillin does not affect Ca++- or K+-mediated membrane events; other data suggest that it produces burst generation in hippocampal pyramidal neurons by attenuating gamma-aminobutyric acid-mediated synaptic inhibition, which in turn ordinarily limits intrinsic bursting.
Approximately 5,000 new cases of neurosyphilis may occur in the United States each year. General paresis and tabes dorsalis, however, have become relatively rare since the introduction of penicillin. Seizures, neuro-ophthalmologic symptoms, stroke and acute meningoencephalitis are currently the most common manifestations of neurosyphilis. In more than a third of patients with neurosyphilis, nontreponemal tests for syphilis (such as VDRL) are negative and should not be used to exclude the diagnosis. Specific treponemal tests are more sensitive and more specific. Examination of the cerebrospinal fluid may show no abnormalities in neurosyphilis and is not an infallible guide to the activity of the infection. Penicillin is the only proven antibiotic treatment of neurosyphilis. However, low-dose regimens do not produce spirocheticidal concentrations in the brain, and high-dose penicillin therapy is recommended to insure eradication of the spirochetes. Doxycycline, a tetracycline derivation that achieves relatively high concentration in the brain, may also be effective.
1. A long-lasting afterhyperpolarization (AHP) follows current-induced repetitive firing in hippocampal CA1 neurons studied in vitro. A 10-25% increase in membrane slope conductance occurs during the AHP, suggesting that it may be mediated by an increased conductance to either K+ or Cl-. 2. Intracellular Cl- iontophoresis does not alter the AHP but does attenuate the IPSP. In contrast Ba2+, a cation that can decrease K+ conductance, eliminates the AHP but not the IPSP. These findings suggest the AHP is produced by a long-lasting increased conductance to K+, and is distinct from the IPSP. 3. Mn2+, a Ca2+-channel blocker, eliminates the AHP. In comparison, the AHP persists in the presence of the Na+-channel blocker, tetrodotoxin (TTX), and appears to be temporally associated with TTX-resistant "Ca2+ spikes." It is concluded that AHP is probably activated by Ca2+ influx. 4. These observations indicate that the AHP may be produced by a Ca2+ activated K+ current. A balance between cellular depolarization produced by Ca2+ entry and repolarization generated by a Ca2+-activated K+ current appears to operate to control excitability in some mammalian cortical neurons as it does in molluscan neurons. Disruption of this balance by Ba2+ produces spontaneous membrane-potential oscillations and recurrent burst firing in hippocampal neurons. Increases in the magnitude and duration of Ca2+ depolarization and/or decreases in the Ca2+-activated, K+-mediated repolarization may be mechanisms that lead to spontaneous, epileptiform bursting in mammalian cortical neurons.
1. Anomalous rectification occurred in 54 of 56 hippocampal CA1 neurons studied in vitro. This phenomenon is characterized by a progressive increase in input resistance with membrane depolarization. An average increase in membrane resistance of 45% occurred over a 15-mV region of membrane potential immediately subthreshold to cellular firing. 2. Both Mn2+, a Ca+ antagonist, and tetrodotoxin (TTX), a neurotoxin that blocks regenerative Na+ currents, eliminated anomalous rectification. Ba2+, which can both contribute to intracellular cation influx as well as reduce K+ conductance, increased the magnitude of anomalous rectification. The observations are indirect evidence indicating that a Ca2+-Na+ current may produce the inward-going rectification. 3. Enhancement of anomalous rectification by Ba2+ was associated with the onset of membrane oscillations and spontaneous bursts of repetitive discharges. The magnitude of anomalous rectification may be one factor that predisposes some cortical neurons to bursting behavior.
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Two patients with disulfiram-(Antabuse-)induced encephalopathy exhibited paranoid ideas, disorientation, impaired memory, ataxia, dysarthria, snout and grasp reflexes, and abnormal electroencephalograms. The first patient developed symptoms on two occasions, each time after disulfiram administration. The second patient experienced a generalized seizure followed by fulminant psychosis three weeks after starting disulfiram therapy. Spinal fluid examination in the latter patient revealed a low homovanillic acid (HVA) level. Since disulfiram inhibits dopamine oxidation, disulfiram-induced encephalopathy may be related to excess dopaminergic activity in the central nervous system.
Review of the neurological complications encountered in 83 patients who received cardiac homografts over a seven-year period leads to the following conclusions: (1) Neurological disorders are common in transplant recipients, occurring in over 50 per cent of patients. (2) Infection was the single most frequent cause of the neurological dysfunction, being responsible for one-third of all CNS complications. (3) The infective organisms were typically those considered to be usually of low pathogenicity: fungi, viruses, protozoa and an uncommon bacterial strain. (4) Other clinical neurological syndromes were related to vascular lesions, often apparently from cerebral ischaemia or infarction occurring during the surgical procedure, metabolic encephalopathies, cerebral microglioma, acute psychotic episodes and back pain from vertebral compression fractures. (5) The infectious complications and probably the development of neoplasms de novo, are related to immunosuppressive therapy which impairs virtually all host defence mechanisms and alters the nature of the host's response to infective agents or other foreign antigens. (6) Because neurological symptoms and signs were usually those of behavioural changes or deterioration in intellectual performance, the neurological examination was often of little value in diagnosing the nature or even the anatomical site of the neuropathological process. (7) The possibility of an infectious origin of the neurological manifestations must be aggressively pursued even in the absence of fever and a significantly abnormal spinal fluid examination. The diagnostic error made most frequently was to ascribe neurological symptoms erroneously to metabolic disturbances or to "intensive care unit psychosis" when they were in fact due to unrecognized CNS infection. (8) Maintenance of mean cardiopulmonary bypass pressures above 70 mmHg, particularly in patients with known arteriosclerosis, may reduce operative morbidity. (9) Though increased diagnostic accuracy is possible with routine use of a variety of radiological and laboratory techniques, two further requirements probably must be met before a significant reduction in the frequency of neurological complications will occur: the advent of greater immunospecificity in suppressing rejection of the grafted organ while preserving defences against infection; and a more effective armamentarium of antiviral and antifungal drugs.
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