Gastone G. Celesia

Acetylcholine released from cerebral cortex in relation to state of activation

THERE IS a growing amount of experimental evidence to support the view that certain forms of activation of the cerebral cortex may be mediated by acetylcholine ( ACh) . It has long been known that desynchronization of the electrical activity of the cortex comparable to that seen in the transition from the state of sleep to arousal or alertness can be simulated by ACh or by agents which antagonize its hydrolysis such as neostigmine bromide (Prostigmin@) . This forni of activation or “arousal” is blocked by atropine.1-5 Activation to epileptiform discharge by ACh has also been demonstrated by numerous investigators.6-9 More direct evidence has been obtained by measurements of the “bound or “stored” concentration of ACh in cerebral tissue during different states of activation, as in the studies of Richter and Crosslandlo who found an increase in the tissue ACh, that is, the “bound form, during anesthesia as compared to the state of wakefulness and a marked decrease during convulsive seizures. These results were confirmed by Pepeu and Mantegazzinill in experiments involving a hemisection of the midbrain. These authors found that the hemisphere showing electrical activity characteristic of sleep contained more bound ACh than the opposite hemisphere which showed an arousal pattern in the electroencephalogram (EEG), thereby concluding that more ACh was being released in the “waking” half of the brain. Direct measurements of the rate of release of ACh from the surface of the cerebral cortex have also been shown to vary with its degree of activation by the use of a profusion chamber placed in the skull over the cortex in which could be placed an “eserinized” physiological salt solution.12-14 These studies have shown

Auditory cortical areas of man.

CO\f l ’CTEl l AVERAGING TECHNIQUES to extract small signals from the spontaneous background rhythms have been applied in recent years to the study of cortical sensory areas in mail during neurosurgical procedures. Somatosensoryevoked responses have been recorded directly from the cerebral cortex and thalamic nuclei,1-4 and detailed reports are therefore available on the configuration, latency, and physiological characteristics of these responses. By contrast, comparable studies oil the central auditory system are few. Celesia et x1.z recorded evoked potentials to clicks from the posterior part of the first temporal gyriis (nlso referred to as the superior tempoi~al gyrus) and the parietal and frontal opercnlnm, but ndmittedly they did not record from the trans\reuse temporal gyri. Sem-Jacobsen et al.6 and Chatriaii et a1.7 obtained single evoked potentials to click stimulation from the human cortex with the use of chronically implanted electrodes. However, it is doubtful if their electrode placed on the superior surface of the tempoi-a1 lobe recorded primary auditory responses. A systematic exploration of the superior temporal plane was undertaken in the present work to determine the nature and location of the human primary auditory sensory area.

Positive spontaneous visual phenomena limited to the hemianopic field in lesions of central visual pathways

We prospectively studied 32 patients with ischemic infarction of the retrochiasmal visual pathways.Positive spontaneous visual phenomena (PSVP) in the blind hemifield were present in 13 patients (41%). The PSVP were subdivided into phosphenes, photopsias, visual hallucinations, palinopsia, and agitated delirium with hemianopia. PSVP were never associated with auditory or other sensory positive phenomena, except in patients with agitated delirium. Patients with photopsias, phosphenes, palinopsia, and visual hallucinations had similar lesions in MRI/CT, suggesting no anatomic area unique for these four phenomena. However, there was a significant difference in the severity of associated neurologic deficits between hemianopic patients with and without PSVP. Larger lesions destroying anteriorly located visual association areas precluded the development of PSVP, which may be related to release from inhibitory input of visual regions bordering the damaged area. Patients with the syndrome of agitated delirium and hemianopia had specific lesions involving the mesial aspect of the occipital lobe, the parahippocampal gyrus, and hippocampus. NEUROLOGY 1996;47: 408-417

Evoked potential techniques in the evaluation of visual function.

Visual evoked potentials (VEPs) can be used in a multitude of ways to assess the various levels of visual processing. The human visual system consists of multiple, parallel channels which process different information, and each channel constitutes a set of sequential processes. An algorithm of sequential steps that can be used to assess visual function is reviewed. The pathophysiology of retinal, anterior visual pathways and retrochiasmal pathways can be objectively evaluated by VEPs.

Visual electroencephalographic computer analysis (VECA) A new electrophysiologic test for the diagnosis of optic nerve lesions

The function of optic pathways was studied by visual electroencephalographic computer analysis (VECA). Pattern and flash stimuli were used. The VECA profile was abnormal in two types of lesions: pathology involving the eye, and pathology involving the optic nerve. When ocular pathology is excluded, an abnormal profile indicates optic nerve dysfunction. Of the multiple sclerosis patients tested, 77 percent had an abnormal VECA profile. The test was always abnormal in patients with optic neuritis. Delayed visual evoked responses occurred in 18 of 29 multiple sclerosis patients judged to be clinically without visual deficits. VECA is reliable and sensitive for detecting clinical and subclinical optic nerve pathology.

Regional alterations in M1 muscarinic receptor-G protein coupling in Alzheimer's disease

Previous studies examining the functional status of cortical muscarinic cholinergic M1 receptors have demonstrated an impairment in receptor-G protein coupling in Alzheimers disease (AD) as measured by the inability of the receptor to form a high affinity agonist binding site. In order to investigate whether this alteration was a global phenomenon or a regional specific defect in signal transduction, we examined agonist binding at M1 receptors in three brain areas (superior frontal cortex, Brodmann areas 8 and 9; primary visual cortex, Brodmann area 17; and the dorsal striatum) within the same brain in controls and moderate to severe AD cases. Competition binding studies using the M1 antagonist 3H-pirenzepine (4 nM) in the presence of varying concentrations of the cholinergic agonist carbachol (50 nM to 1 mM) were performed in the presence and absence of GppNHp (100 microM), a non-hydrolyzable analog of GTP. In control membrane preparations, computer-assisted analysis of antagonist-agonist competition curves revealed that M1 receptor agonist binding fit a two site model with high and low affinity states in all three brain areas in the absence of GppNHp but only a single site in the presence of GppNHp. This is consistent with the ternary complex model of G protein-linked receptors. In contrast, curves obtained from both cortical regions from AD brains fit a single site model with low affinity in the presence or absence of GppNHp. On the other hand, agonist binding data obtained from the dorsal striatum of AD cases exhibited a two site fit, similar to that seen in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Disorders of membrane channels or channelopathies.

OBJECTIVE To review the structure and function of membrane ion channels with special emphasis on inherited nervous system channel disorders or channelopathies. RESULTS Channels are pores in the cell membrane. Through these pores ions flow across the membrane and depolarize or hyperpolarize the cell. Channels can be classified into 3 types: non-gated, directly gated and second messenger gated channels. Among the important directly gated channels are voltage gated (Na(+), K(+), Ca(2+), Cl(-)) and ligand gated (ACh, Glutamate, GABA, Glycine) channels. Channels are macromolecular protein complexes within the lipid membrane. They are divided into distinct protein units called subunits. Each subunit has a specific function and is encoded by a different gene. The following inherited channelopathies are described. (1) Sodium channelopathies: familial generalized epilepsy with febrile seizures plus, hyperkalemic periodic paralysis, paramyotonias, hypokalemic periodic paralysis; (2) potassium channelopathies: benign infantile epilepsy, episodic ataxia type 1; (3) calcium channelopathies: episodic ataxia type 2, spinocerebellar ataxia type 6, familial hemiplegic migraine, hypokalemic periodic paralysis, central core disease, malignant hyperthermia syndrome, congenital stationary night blindness; (4) chloride channelopathies: myotonia congenitas; (5) ACh receptor channelopathies: autosomal dominant frontal lobe nocturnal epilepsy, congenital myasthenic syndromes; (6) glycine receptor channelopathies: hyperekplexia. CONCLUSIONS Studies of human inherited channelopathies have clarified the functions of many ion channels. More than one gene may regulate a function in a channel, thus different genetic mutations may manifest with the same disorder. The complex picture of the genetic and molecular structures of channels will require frequent updates.

Prognostic significance of EEG triphasic waves in patients with altered state of consciousness.

Triphasic waves (TWs) are a distinctive, but nonspecific, EEG pattern found in metabolic encephalopathies and a variety of other neurologic conditions. The prognostic value of TWs was studied in 30 patients with altered state of consciousness. Patients were either comatose (18 patients) or very lethargic (12 patients). Triphasic waves were the dominant EEG pattern, present for at least 35% of the tracing. The etiology of their underlying encephalopathy was multiple metabolic derangements (12 patients), hepatorenal syndrome (5 patients), renal failure (4 patients), hypoxic encephalopathy (4 patients), hepatic failure (3 patients), hyponatremia (1 patient), and hypoglycemia (1 patient). Patients were followed up to 22 months. Fifty percent of the subjects died within 30 days of recording TWs. The overall mortality was 77%. Seven patients (23%) have survived, but only three patients (10%) are neurologically normal. In conclusion, TWs occur most often in patients with metabolic encephalopathies, cannot be used to distinguish different diagnostic entities, and indicate a poor prognosis for survival.

The effects of age on steady-state pattern electroretinograms and visual evoked potentials

Steady-state pattern-reversal electroretinograms and visual evoked potentials were simultaneously recorded in two groups of young and elderly normal volunteers. The young group consisted of 23 subjects (13 women and 10 men) aged 18 to 28 years, and the elderly group consisted of 24 subjects (11 women and 13 men) aged 58 to 77 years. Stimuli were square-wave gratings ranging in spatial frequency from 0.5 to 6 c/deg and phase reversed at a frequency of 4 Hz. Pattern-reversal electroretinograms and visual evoked potentials consisted of a prominent second and a smaller fourth harmonic response. Spatial frequency-amplitude functions of the pattern-reversal electroretinogram second and fourth harmonics were similar for the young and elderly groups. The mean fourth harmonic phase was significantly shifted in elderly subjects compared with young subjects for all spatial frequencies tested. Spatial frequency tuning was observed for amplitude and phase functions of the visual evoked potential second and fourth harmonic responses for both age groups. Age had a significant effect on phase for spatial frequencies above 1.5 c/deg. Amplitude of the fourth harmonic was significantly lower for the elderly group at 1.5–4 c/deg. Phase was significantly different between groups for spatial frequencies below 3 c/deg. Our results suggest that aging influences both retinal and central visual pathways. Aging differentially affected the visual evoked potential second and fourth harmonic responses, suggesting different neuronal origins for these components.

Simultaneous recording of pattern electroretinogram and visual evoked responses in neuro‐ophthalmologic disorders

Simultaneous pattern electroretinograms (P-ERG) and pattern visual evoked potentials (P-VEP) to transient and steady-state checkerboard pattern reversal were recorded in 52 normal volunteers. Twenty-seven patients were also studied. Three patterns of abnormalities emerged. Pattern 1 with prolonged P-ERG, prolonged P-VEP, and normal retino-cortical time (RCT) was found exclusively in early maculopathies. Pattern 2 with normal P-ERG, prolonged P-VEP, and prolonged RCT was found in optic nerve lesions without optic atrophy, probably indicating the presence of a demyelinating lesion of the optic nerve. Pattern 3, with very small or absent P-ERG and P-VEP, was observed in both maculopathies and optic atrophies.