Milton M. Gross

Acute Alcohol Withdrawal Syndrome

Delirium tremens and related clinical states have been part of the human condition since antiquity (Zilboorg and Henry, 1941). However little was known and less was written about them until the end of the eighteenth century, when the diagnosis and treatment of this group of illnesses were delineated for the first time (Lettsom, 1787; Pearson, 1801, 1813; Sutton, 1813). This was followed by a series of confirmatory observations, some of which also contributed new data on prognostic factors (Armstrong, 1813; Klapp, 1817; Channing, 1819; Snowden, 1820; Hayward, 1822; Staughton, 1822; Coates, 1827; Wright, 1830; Carter, 1830; Jackson, 1830; Ware, 1838). The subsequent sustained proliferation of publications on these clinical states have increased our knowledge and attest to the continuing interest and importance of this field of study.

Auditory evoked response comparison during counting clicks and reading

Abstract The shift from a casual task directed away from auditory stimuli to a task requiring a low order of effort directed to the auditory stimuli produced significant changes in the 4 major amplitudes and the total duration of the auditory evoked response.

An Improved Quantitative System for Assessing the Acute Alcoholic Psychoses and Related States (TSA and SSA)

The problem of studying and treating the acute alcoholic psychoses and related states has been substantially burdened by the inadequacies of the methods of assessing the condition of the patients at the time of initial contact and during their subsequent course. A new, reliable alternative has been developed and will be described which is an improved version of a previously published reliable quantitative assessment (Gross et al., 1971).

EXPERIMENTAL STUDY OF SLEEP IN CHRONIC ALCOHOLICS BEFORE, DURING, AND AFTER FOUR DAYS OF HEAVY DRINKING, WITH A NONDRINKING COMPARISON*

Since the advent of a psychophysiologic anatomy of sleep, it has been hoped that it would prove relevant to clinical problems. One area where its relevance has become increasingly apparent has been in studies of the acute alcohol withdrawal states and the intoxication that precedes them. Clinical studies have suggested relations between increased stage I REM and hallucinations during withdrawal.1-6 The clinical data have also suggested a connection between reduced slow-wave sleep and withdrawal manifestations in addition to hallucination^.^-* It has also been proposed that the marked reduction of the slow-wave sleep associated with the withdrawal may be a prerequisite for the unusually high levels of stage I REM and h a l l u c i n a t i ~ n s . ~ ~ J ~ A pilot experimental study suggested a biphasic effect of alcohol on stage I REM and the slow-wave sleep, in which the withdrawal effects appeared to be the reverse of the alcohol intake effect.24 Mello and Mendelsonlo have drawn attention to sleep-wake fragmentation of sleep during drinking and withdrawal and questioned the relation between insomnia and withdrawal. Johnson and co-workerss drew attention to sleep fragmentation, in terms of stage changes during withdrawal. Most recently, sleep in the nondrinking, basal state of the chronic alcoholic has also received considerable attention.6J1 A partial presentation of the experimental data to follow, as well as an extensive review of the literature, have been previously r e p ~ r t e d . ~

Quantitative Changes of Signs and Symptoms Associated with Acute Alcohol Withdrawal: Incidence, Severity and Circadian Effects in Experimental Studies of Alcoholics

A quantitative phenomenological approach to the alcohol withdrawal syndrome in man offers major advantages to the investigator and clinician that are not provided by the current nosology of the withdrawal. These advantages have been discussed at length elsewhere (Gross et al., 1974). A clinical instrument was developed for the purpose of a quantitative phenomenological assessment of the alcohol withdrawal syndrome, the Total Severity Assessment of alcohol withdrawal (TSA). This instrument was based on a review of the literature, observations over thirteen years of approximately fifteen thousand patients in alcohol withdrawal, and extensive clinical trials, several of which have been reported (Gross et al., 1968, Gross et al., 1971a, Gross et al., 1971b, Gross et al., 1973, Gross et al., 1974). The TSA has been applied in experimental studies of intoxication and withdrawal in alcoholic volunteers. In an earlier communication, the prevalence of the signs and symptoms associated with acute alcohol withdrawal during experimental studies were reported (Gross and Lewis, 1973). This communication will examine the incidence and severity of the signs and symptoms during experimental studies of intoxication and withdrawal in an enlarged sample. Circadian effects on temperature changes will also be described.

The Relation Between Baseline Slow Wave Sleep and the Slow Wave Sleep Response to Alcohol in Alcoholics

Important advances in the psychophysiological studies of sleep, triggered by the breakthroughs of Aserinsky and Kleitman (1953) and Dement and Kleitman (1957), led to investigations of the possible relevance of such studies to psychopathology. In alcoholics, striking departures from normal sleep psychophysiology were observed during and following acute intoxication and withdrawal (see reviews by Johnson, 1971, Gross et al., 1971, Williams and Salamy, 1972 and Gross et al., 1974). The disturbances observed in alcoholics involved the rhythmicity and composition of sleep. Prominent among the disturbances of sleep composition were those involving Slow Wave Sleep (SWS).

Sleep Changes Induced by 4 and 6 Days of Experimental Alcoholization and Withdrawal in Humans

The delineation of five somewhat sequential stages of sleep which occurred rhythmically in approximately 90 minute cycles in normal adults generated considerable interest in those who saw in it the possibility for investigating the nature of these stages of sleep and their relation to normal and pathological states.

Correlation of Urinary Biogenic Amines with Sleep Stages in Chronic Alcoholization and Withdrawal

The chronic administration of alcohol causes dramatic changes in the urinary excretion of biogenic amines and their metabolites at the same time that it causes equally dramatic changes in the sleep pattern. Since the stages of sleep are said to be related to biogenic amine metabolism in the brain, it seemed reasonable to investigate the possible relationship between these two widely separated sets of phenomena.

Slow Wave Sleep and Carry-over of Functional Tolerance and Physical Dependence in Alcoholics

Alcohol affects sleep. In alcoholics, profound sleep changes have been observed clinically and experimentally before, during and after a period of heavy alcohol intake. Elucidation of the alcohol-sleep interactions may illuminate mechanisms involved in alcoholism. This communication will focus on the post-drinking Slow Wave Sleep (SWS) which tends to be decreased initially and gradually recovers. More specifically the post-drinking SWS will be examined in relation to the rate of reacquisition of functional tolerance and physical dependence in a subsequent drinking episode.

Recovery Function and Clinical Symptomatology in Acute Alcoholization and Withdrawal

Withdrawal has often been considered a phenomenon which occurs only after the cessation of long-term alcohol intake. The occurrence of withdrawal signs and symptoms upon cessation of alcohol ingestion is evidence of physiological dependence. It has also been postulated by Seevers and Deneau (1964) that physical dependence is characterized by hyperexcitability of the central nervous system. Consequently, we recently undertook to study changes in brain excitability of alcoholics, during alcoholization and withdrawal. We used the recovery function of somatosensory evoked potentials to assess changes in CNS excitability. Our findings (Begleiter, Porjesz and Yerre, in press) demonstrated that an increase of central nervous system excitability results from the cessation of alcohol intake, even after short periods of drinking. The state of hyperexcitability increases as drinking progresses and appears to reach a peak approximately 34 hours subsequent to withdrawal from prolonged alcohol ingestion. Three days after cessation of alcohol intake, our recovery function values return to normal. Our data support the hypothesis that partial withdrawal is manifested by a latent rebound hyperexcitability which occurs subsequent to depression of the central nervous system by alcohol.