Electroencephalographic Findings in Phencyclidine Intoxication James J.
\s=b\ The
Stockard, MD; Sarah S. Werner, MD; John A. Aalbers, MD; Keith H. Chiappa, MD first
report
of
electroencephalo-
graphic findings in clinically encountered phencyclidine intoxication is presented. When first seen, the patient was in a coma, initially distinguished only by nystagmus, waxy rigidity of the extremities, and an EEG with a widespread, sinusoidal theta rhythm interrupted every few seconds by periodic slow-wave complexes. The similarity of the EEG to that of deep ketamine anesthesia suggested intoxication
with
a
ketamine-related
(phenylcyclohexylamine) drug. Phencyclidine, the prototype of the phenylcyclohexylamine compounds and a widely abused hallucinogen, was subsequently identified in the urine and blood. (Arch Neurol 33:200-203, 1976)
Phencycl idine hydrochloride, l-(l-phenylcyclohexyl) piperidine,
or
introduced in the late 1950s as an intravenous general anesthetic that was nontoxic, nonflammable, and pro¬ duced minimal cardiorespiratory de¬ pression.1 These clinical advantages were unfortunately offset by its prolonged duration of action and
was
-
psychotomimetie effects,3 properties
Accepted for publication Sept 24, 1975. From the Clinical Neurophysiology Laboratories, Department of Neurosciences, University of California (San Diego) School of Medicine, La Jolla, Calif. Reprint requests to EEG Laboratory, University Hospital, 225 W Dickinson St, San Diego, CA 92103 (Dr Stockard).
that have contributed to the emer¬ gence of phencyclidine as a major drug of abuse in the United States.4-0 Known on the streets as "angel dust,"
"angel mist," "PCP," "hog," and "peace pills," phencyclidine may be taken orally, parenterally, or inhaled in powdered form. It is present in a wide variety of hallucinogen prepara¬ tions that are falsely labeled as pure LSD, mescaline, THC (tetrahydrocannabinol), psilocybin, STP (2,5-dimeco¬ thoxy-4-methylamphetamine), caine, 3,4-methylenedioxyampheta-
combinations of these.7-9 Severe phencyclidine intoxication can produce "coma" in the sense of unarousable unresponsiveness, but it remains unclear whether conscious¬ ness is actually lost secondary to the brain stem effects of the drug or is merely altered at limbic and neocortical levels; the latter mechanism is suggested by some of the clinical pre¬ sentations of phencyclidine overdose, which, in addition to simple obtunda¬ tion, can include a condition resem¬ bling akinetic mutism with catalepsy, a fugue-like state with automatisms, or even grand mal status epilepticus.10 Because of the confusing clinical manifestations and increasing inci¬ dence of phencyclidine overdose,10-14 the electroencephalographic effects are of potential diagnostic impor¬
mine,
tance.
or
METHOD Pour EEG recordings were obtained in this case at 8,12, 36, and 72 hours after the patient's admission to the intensive care unit (ICU). Bipolar and unipolar recordings were performed with an eight-channel electroencephalograph (time constant of 0.16 second, high-frequency filter of 70 hertz) from a 10-20 system placement of tin-tin chloride disc electrodes applied with collodion. A high-frequency cutoff (—3 dB point) of 35 Hz was employed during the illustrated portions of the EEG records in order to reduce contamination by electro¬
myographic (EMG) potentials. Periorbital, perioral, and submental electrodes were applied with adhesive paste for the record¬ ing of electro-oculographic (EOG), glossokinetic, and EMG potentials, respectively. Polygraphie data were recorded either on
FM tape recorder or, when recorded on paper, were reconverted to "live" analog form with an automatic curve reader. Analog EEG data were then digitized and subjected to power spectral analysis with a an
digital computer. Serum phencyclidine con¬ centrations were determined by gas-liquid Chromatographie analysis, and urine phen¬ cyclidine analyses employed thin-layer chromatography. Serial neurologic exams were performed at four- to six-hour inter¬
vals from the time of admission until recovery of consciousness 48 hours later.
REPORT OF A CASE A 25-year-old man was admitted to the ICU, unresponsive and immobile, with shallow, regular respirations at 14 per minute, blood pressure of 160/95 mm Hg,
Downloaded From: http://archneur.jamanetwork.com/ by a University of California - San Diego User on 06/05/2015
pulse
rate of 102 beats per
minute, rectal
Ice-water calorie stimulation produced tonic conjugate ocular deviation toward the irrigated ear. Deep tendon reflexes were symmetrically increased, and there was a generalized increase in muscle tone with waxy rigidity of the extremities. There was unsustained clonus of both ankles, but no Babinski or other pathologic reflexes. There was no response to intense, repeti¬ tive sensory stimulation, including deep pain and trachéal suctioning. Lumbar puncture, cerebrospinal fluid examination, chest roentgenogram, electrocardiogram,
temperature of 37.7 C, and PaoL,/Paco„/pH
(room air) of 59/44/7.44. The patient was intubated and given mechanically con¬ trolled ventilation, after which the arterial blood gases normalized. Initial neurologic examination indicated reactive 3-mm pu¬ pils bilaterally, with hippus and intermit¬ tent, tonic, downward deviation of the eyes. Prominent horizontal and rotatory nystagmus were observed on separate occasions. Corneal, oculocephalic, cough, gag, and ciliospinal reflexes were intact.
routine blood chemistry tests, complete blood cell count, and urinalysis were unre¬ markable. The initial EEG recorded eight hours after admission showed nearly continuous, generalized sinusoidal theta activity that was interrupted approximately every four seconds by slow-wave discharges (Fig 1). Between periodic slow-wave complexes, the diffuse theta activity was unreactive to photic, auditory, and tactile stimulation and to deep pain and eye-opening. It remained monorhythmic at 5.75 ± 0.25 Hz
Fpl-F3 F3-C3
vvvA/wvvvwV\/^mm/^^
C3-P3
mamaa/vAa/W^'V/nAA^^ ^ ^
P3-01
/\ _ ^^
^^
Fp2-F4 '^A^^^^hrAy^^^^ f4-QA.
/\ ~
/\/ ^·/ ^ / \^^ /WV^^A
-PA
/^
^^
4-02 75uV
I_
I second
Fig 1.—Bipolar EEG recording obtained approximately 12 hours after inhalation of phencyclidine, showing diffuse, monorhythmic theta activity with periodic slow-wave complexes. Complexes not
synchronized with any detectable external events (including respiration), and no associated ocular or prosopoglossopharyngeal movements apparent.
Fib 2.—Unipolar EEG recording obtained approximately 16 hours after phencyclidine intake. Note parietal predominance of theta rhythm and progressive fronto-occipital latency lag of delta complexes. Desynchronizations of theta rhythm preceded electro-oculographic (EOG) and glossokinetic (GKP) potentials
generated by
Fp1 Fp2
-
A1
V*
A2
Wv\MAMM/W\/V^^/7^
73
_
A"|
V\l\ rJV\µ^J^AÍ r í\ys^^ ^^
T4
—
A2
P3
-
A1
P4
-
A2
-
/ 1/^ \ /
/ \/ ^ ^ ^^
associated eye and tongue movements. The EOG contribution to large positive wave of the more frontal EEG complexes can be appreciated. Bottom tracing indicates trig¬ gering of respirator.
/'''% / >/\ ^^ ^^
A/WWvVVWWW7"^^ ^ /^
EOG GKP/ ECG " *—,u»Ji~«*'L-~«V~yV,
RFSPÍMA-Ü 100 µ V I second
Downloaded From: http://archneur.jamanetwork.com/ by a University of California - San Diego User on 06/05/2015
/"^SfvANWvW
period of hours (as shown by sequen¬ spectral analyses) and was maximal in amplitude in the centroparietal regions, ranging up to µ . Twelve hours after the patient's admis¬ sion, the intermittent desynchronizations of the diffuse theta rhythm (now 6.0 Hz) had become less frequent and less periodic over a
EEG
POWER
SPECTRA
CONVENTIONAL
EEG
50 |jV
tial
and
were now
associated with
a
stereo¬
typed complex of motor manifestationstransient eye-opening and vertical nystag¬ mus, mouth-opening with tongue protru¬ sion, and bisynchronous myoclonic arm flexion. The periodic desynchronizations of the theta rhythm were now initiated by a bilaterally synchronous slow or sharp wave, highest in amplitude anteriorly and show¬ ing frontooccipital lag, which preceded the onset of the electro-oculographic and glossokinetic potentials resulting from the
associated eye and tongue movements (Fig A short time later, the patient devel¬ oped repetitive, stereotyped automatisms that consisted of opening the eyes, raising the right arm, and staring at the raised hand for several seconds while smacking his lips. Other stereotyped movements of the extremities sometimes accompanied the automatism described above. Ten milli¬ grams of diazepam given intravenously slowed the theta rhythm by 2 Hz and reduced its amplitude by 30µ , while abol¬ ishing the automatic movements (Fig 3). The slow-wave rhythm was never com¬ pletely desynchronized, however, and with¬ in eight minutes of the diazepam infusion it had increased in amplitude and frequen¬ cy again to 50µ and 4 Hz as the stereo¬ typed extremity, ocular and prosopoglossopharyngeal movements returned. Subse¬ quently, the synchronous arm jerks reap¬ peared and increased in frequency, culmi¬ nating in two clonic seizures. Phenytoin therapy, administered intravenously, was begun at 50 mg/hr, and no further clinical seizure activity was noted. By this time, phencyclidine was detected in urine, and a serum phencyclidine concentration of 0Mpg/m\ was subsequently determined. Thirty-six hours after admission, the patient remained stuporous, responding only to trachéal suctioning. Intermittent vertical nystagmus was still present, but the periodic motor manifestations were absent. There was still sustained cataleptic posturing of the extremities in virtually any position into which they were passively moved. Spontaneous semipurposeful move¬ ments occurred continually, unmodified by stimulation, but deep pain resulted in decorticate posturing. The EEG at this time showed continuous generalized sinu¬ soidal 30µ to 50µ , 7.5 Hz activity, maximal posteriorly, which remained unreactive to eye-opening, but desynchro-
2).
eight minutes after diazepam
;
spontaneous
movements
return
^v^sVuv/v\AA"VA/V four minutes
following diazepam; unresponsive,
no
movements
immediately following intravenous infusion of 10 mg. diazepam
over
2 min.
completely unresponsive but with spontaneous movement
Fig 3.—Diazepam-induced slowing and desynchronization of monorhythmic theta activity associated with disappearance of spontaneous stereotyped movements. Resynchronization and acceleration of slow-wave rhythm began about eight minutes later accompanied by reappearance of motor automatisms. Each of four samples consists of vertically compressed power spectra from nine successive four-second epochs of primary EEG data. Power is proportional to peak heights and is expressed with 0.25 Hz resolution. A representative four-second epoch of primary EEG data is plotted to right of each spectral block; slight irregularities in latter tracings are artifacts of computer analysis. Parieto-occipital EEG derivation. nized in response to trachéal suction. Forty hours after admission, the patient was extubated, and eight hours later he regained consciousness (appropriate verbal responsiveness). Seventy-two hours after admission, neurologic recovery was com¬ plete, and the EEG had returned to within normal limits, with a symmetric, reactive 8.5-Hz alpha rhythm. The patient stated
thing he remembered prior to awakening on the third hospital day was inhaling a large amount of "angel dust" on the night of admission. that the last
COMMENT
Rhythmic slowing of EEG back¬ ground activity has been reported in human volunteers receiving 0.1 to 0.3
Downloaded From: http://archneur.jamanetwork.com/ by a University of California - San Diego User on 06/05/2015
mg/kg phencyclidine hydrochloride intravenously,117'1'1 but the periodic EEG events seen early in this case were not observed in the experimental studies. The EEG and neurologic manifestations produced experimen¬ tally by 0.1 to 0.3 mg/kg phencyclidine hydrochloride given intravenously did
resemble those seen 36 hours after admission in our patient, at which time the serum concentration had presumably fallen well below the
earlier value. In one experimental human study,1 intravenous doses of 0.5 to 1.0 mg/kg phencyclidine hy¬ drochloride induced seizures, but the EEG effects were not reported. The EEG pattern of deep phency¬ clidine obtundation (Fig 1 and 2) is sufficiently specific to be of diag¬ nostic importance and, in fact, ini¬ tially suggested the diagnosis in the case presented; we had observed a similar pattern before only in patients deeply anesthetized with ketamine, a derivative of phencyclidine. Like their parent compound, ketamine (2-[orthochlorophenyl] 2- [methylamino] cyclohexanone) and other cyclohexylamine derivatives can produce rhythmic the¬ ta activity, which, at higher doses, is interrupted by periodic slow- or sharpwave complexes.171* Ketamine pro¬ duces a "cataleptoid" state of unre-
sponsiveness similar to that induced by phencyclidine and is gaining popu¬ larity as a street hallucinogen."> -" Thus, an electroclinical presentation similar to that described above might also be anticipated with ketamine intoxication.
This investigation was supported in part by an Epilepsy Foundation of American fellowship (Dr Stockard), and by US Public Health Service grant NS 08962. Kenneth R. Hanson assisted in the computer analysis of the EEG data. Susan Sampson and Gina Dronet aided in the preparation of the manuscript. R. G. Bickford, MB, FRCP, supplied recording and computing equipment.
Nonproprietary Name and Trademark of Drug
Phencyclidine hydrochloride-Serwî/ton. References 1. Greifenstein FE, DeVault M, Yoshitaki J, et al: A study of l-aryl cyclohexyl amine for anesthesia. Anesth Analg 37:283-294, 1958. 2. Johnstone M, Evans V, Baigel S: Sernyl (C1395) in clinical anesthesia. Br J Anesth 31:433\x=req-\ 439, 1959. 3. Luby ED, Cohen BD, Rosenbaum G, et al: Study of a new schizophrenomimetic drug\p=m-\ Sernyl. Arch Neurol Psychiatry 81:363-369, 1959. 4. Rainey JM, Crowder MK: Prevalence of phencyclidine in street drug preparations. N Engl J Med 290:466-467, 1974. 5. Rainey JM, Crowder MK: Ketamine or
phencyclidine. JAMA 230:824, 1974. 6. The perils of PCP. Drug Enforcement 1:8-9, 1974.
7. Hart JB, McChesney JC, Grief M: Composition of illicit drugs and the use of drug analysis and abuse abatement. J Psychedelic Drugs 5:83\x=req-\ 88, 1972. 8. Gupta RL, Montgomery SH, Lundberg GD: Quantitative determinations of street drugs in the Los Angeles area. Clin Toxicol 7:241-254, 1974. 9. Schnoll SH, Vogel WH: Analysis of "street drugs." N Engl J Med 284:791, 1971. 10. Kessler GF, Demers LM, Berlin C, et al: Phencyclidine and fatal status epilepticus. N Engl J Med 291:979, 1974. 11. Stein JI: Phencyclidine induced psychosis: The need to avoid unnecessary sensory influx. Milit Med 138:590-591, 1973. 12. Liden CB, Lovejoy FH, Costello CE: Phencyclidine (Sernylan) poisoning. Pediatr Pharmacol Ther 83:844-845, 1974. 13. Dandavino R, Friborg J, Beaudry C, et al: Un cas d'intoxication aigu\l=e"\a la phencyclidine avec atteinte musculaire importante et insuffisance r\l=e'\naleaigu\l=e"\. Union Med Can 104:59-60, 1975. 14. Eastman JW, Cohen SN: Hypertensive crisis and death associated with phencyclidine poisoning. JAMA 231:1270-1271, 1975. 15. Meyer JS, Greifenstein F, DeVault M: A new drug causing symptoms of sensory deprivation: Neurological, electroencephalographic and pharmacological effects of Sernyl. J Nerv Ment Dis 129:54-61, 1959. 16. Rodin EA, Luby ED, Meyer JS: Electroencephalographic findings associated with Sernyl infusion. Electroencephalogr Clin Neurophysiol 11:796-798, 1959. 17. Scholler KL, Thies H, Wiemers K: Die Allgemeinanasthesie mit Cyclohexylaminderivaten: Klinische und elektroencephalographische Untersuchungen. Anesthetist 9:163-168, 1960. 18. Corrsen G, Little SC, Tavakoli M: Ketamine and epilepsy. Anesth Analg 53:319-335, 1974. 19. Reier CE: Ketamine\p=m-\dissociativeagent or hallucinogen. N Engl J Med 284:791-792, 1971. 20. Shaffer LL: Ketamine. JAMA 229:763, 1974.
Downloaded From: http://archneur.jamanetwork.com/ by a University of California - San Diego User on 06/05/2015
\s=b\ The
Stockard, MD; Sarah S. Werner, MD; John A. Aalbers, MD; Keith H. Chiappa, MD first
report
of
electroencephalo-
graphic findings in clinically encountered phencyclidine intoxication is presented. When first seen, the patient was in a coma, initially distinguished only by nystagmus, waxy rigidity of the extremities, and an EEG with a widespread, sinusoidal theta rhythm interrupted every few seconds by periodic slow-wave complexes. The similarity of the EEG to that of deep ketamine anesthesia suggested intoxication
with
a
ketamine-related
(phenylcyclohexylamine) drug. Phencyclidine, the prototype of the phenylcyclohexylamine compounds and a widely abused hallucinogen, was subsequently identified in the urine and blood. (Arch Neurol 33:200-203, 1976)
Phencycl idine hydrochloride, l-(l-phenylcyclohexyl) piperidine,
or
introduced in the late 1950s as an intravenous general anesthetic that was nontoxic, nonflammable, and pro¬ duced minimal cardiorespiratory de¬ pression.1 These clinical advantages were unfortunately offset by its prolonged duration of action and
was
-
psychotomimetie effects,3 properties
Accepted for publication Sept 24, 1975. From the Clinical Neurophysiology Laboratories, Department of Neurosciences, University of California (San Diego) School of Medicine, La Jolla, Calif. Reprint requests to EEG Laboratory, University Hospital, 225 W Dickinson St, San Diego, CA 92103 (Dr Stockard).
that have contributed to the emer¬ gence of phencyclidine as a major drug of abuse in the United States.4-0 Known on the streets as "angel dust,"
"angel mist," "PCP," "hog," and "peace pills," phencyclidine may be taken orally, parenterally, or inhaled in powdered form. It is present in a wide variety of hallucinogen prepara¬ tions that are falsely labeled as pure LSD, mescaline, THC (tetrahydrocannabinol), psilocybin, STP (2,5-dimeco¬ thoxy-4-methylamphetamine), caine, 3,4-methylenedioxyampheta-
combinations of these.7-9 Severe phencyclidine intoxication can produce "coma" in the sense of unarousable unresponsiveness, but it remains unclear whether conscious¬ ness is actually lost secondary to the brain stem effects of the drug or is merely altered at limbic and neocortical levels; the latter mechanism is suggested by some of the clinical pre¬ sentations of phencyclidine overdose, which, in addition to simple obtunda¬ tion, can include a condition resem¬ bling akinetic mutism with catalepsy, a fugue-like state with automatisms, or even grand mal status epilepticus.10 Because of the confusing clinical manifestations and increasing inci¬ dence of phencyclidine overdose,10-14 the electroencephalographic effects are of potential diagnostic impor¬
mine,
tance.
or
METHOD Pour EEG recordings were obtained in this case at 8,12, 36, and 72 hours after the patient's admission to the intensive care unit (ICU). Bipolar and unipolar recordings were performed with an eight-channel electroencephalograph (time constant of 0.16 second, high-frequency filter of 70 hertz) from a 10-20 system placement of tin-tin chloride disc electrodes applied with collodion. A high-frequency cutoff (—3 dB point) of 35 Hz was employed during the illustrated portions of the EEG records in order to reduce contamination by electro¬
myographic (EMG) potentials. Periorbital, perioral, and submental electrodes were applied with adhesive paste for the record¬ ing of electro-oculographic (EOG), glossokinetic, and EMG potentials, respectively. Polygraphie data were recorded either on
FM tape recorder or, when recorded on paper, were reconverted to "live" analog form with an automatic curve reader. Analog EEG data were then digitized and subjected to power spectral analysis with a an
digital computer. Serum phencyclidine con¬ centrations were determined by gas-liquid Chromatographie analysis, and urine phen¬ cyclidine analyses employed thin-layer chromatography. Serial neurologic exams were performed at four- to six-hour inter¬
vals from the time of admission until recovery of consciousness 48 hours later.
REPORT OF A CASE A 25-year-old man was admitted to the ICU, unresponsive and immobile, with shallow, regular respirations at 14 per minute, blood pressure of 160/95 mm Hg,
Downloaded From: http://archneur.jamanetwork.com/ by a University of California - San Diego User on 06/05/2015
pulse
rate of 102 beats per
minute, rectal
Ice-water calorie stimulation produced tonic conjugate ocular deviation toward the irrigated ear. Deep tendon reflexes were symmetrically increased, and there was a generalized increase in muscle tone with waxy rigidity of the extremities. There was unsustained clonus of both ankles, but no Babinski or other pathologic reflexes. There was no response to intense, repeti¬ tive sensory stimulation, including deep pain and trachéal suctioning. Lumbar puncture, cerebrospinal fluid examination, chest roentgenogram, electrocardiogram,
temperature of 37.7 C, and PaoL,/Paco„/pH
(room air) of 59/44/7.44. The patient was intubated and given mechanically con¬ trolled ventilation, after which the arterial blood gases normalized. Initial neurologic examination indicated reactive 3-mm pu¬ pils bilaterally, with hippus and intermit¬ tent, tonic, downward deviation of the eyes. Prominent horizontal and rotatory nystagmus were observed on separate occasions. Corneal, oculocephalic, cough, gag, and ciliospinal reflexes were intact.
routine blood chemistry tests, complete blood cell count, and urinalysis were unre¬ markable. The initial EEG recorded eight hours after admission showed nearly continuous, generalized sinusoidal theta activity that was interrupted approximately every four seconds by slow-wave discharges (Fig 1). Between periodic slow-wave complexes, the diffuse theta activity was unreactive to photic, auditory, and tactile stimulation and to deep pain and eye-opening. It remained monorhythmic at 5.75 ± 0.25 Hz
Fpl-F3 F3-C3
vvvA/wvvvwV\/^mm/^^
C3-P3
mamaa/vAa/W^'V/nAA^^ ^ ^
P3-01
/\ _ ^^
^^
Fp2-F4 '^A^^^^hrAy^^^^ f4-QA.
/\ ~
/\/ ^·/ ^ / \^^ /WV^^A
-PA
/^
^^
4-02 75uV
I_
I second
Fig 1.—Bipolar EEG recording obtained approximately 12 hours after inhalation of phencyclidine, showing diffuse, monorhythmic theta activity with periodic slow-wave complexes. Complexes not
synchronized with any detectable external events (including respiration), and no associated ocular or prosopoglossopharyngeal movements apparent.
Fib 2.—Unipolar EEG recording obtained approximately 16 hours after phencyclidine intake. Note parietal predominance of theta rhythm and progressive fronto-occipital latency lag of delta complexes. Desynchronizations of theta rhythm preceded electro-oculographic (EOG) and glossokinetic (GKP) potentials
generated by
Fp1 Fp2
-
A1
V*
A2
Wv\MAMM/W\/V^^/7^
73
_
A"|
V\l\ rJV\µ^J^AÍ r í\ys^^ ^^
T4
—
A2
P3
-
A1
P4
-
A2
-
/ 1/^ \ /
/ \/ ^ ^ ^^
associated eye and tongue movements. The EOG contribution to large positive wave of the more frontal EEG complexes can be appreciated. Bottom tracing indicates trig¬ gering of respirator.
/'''% / >/\ ^^ ^^
A/WWvVVWWW7"^^ ^ /^
EOG GKP/ ECG " *—,u»Ji~«*'L-~«V~yV,
RFSPÍMA-Ü 100 µ V I second
Downloaded From: http://archneur.jamanetwork.com/ by a University of California - San Diego User on 06/05/2015
/"^SfvANWvW
period of hours (as shown by sequen¬ spectral analyses) and was maximal in amplitude in the centroparietal regions, ranging up to µ . Twelve hours after the patient's admis¬ sion, the intermittent desynchronizations of the diffuse theta rhythm (now 6.0 Hz) had become less frequent and less periodic over a
EEG
POWER
SPECTRA
CONVENTIONAL
EEG
50 |jV
tial
and
were now
associated with
a
stereo¬
typed complex of motor manifestationstransient eye-opening and vertical nystag¬ mus, mouth-opening with tongue protru¬ sion, and bisynchronous myoclonic arm flexion. The periodic desynchronizations of the theta rhythm were now initiated by a bilaterally synchronous slow or sharp wave, highest in amplitude anteriorly and show¬ ing frontooccipital lag, which preceded the onset of the electro-oculographic and glossokinetic potentials resulting from the
associated eye and tongue movements (Fig A short time later, the patient devel¬ oped repetitive, stereotyped automatisms that consisted of opening the eyes, raising the right arm, and staring at the raised hand for several seconds while smacking his lips. Other stereotyped movements of the extremities sometimes accompanied the automatism described above. Ten milli¬ grams of diazepam given intravenously slowed the theta rhythm by 2 Hz and reduced its amplitude by 30µ , while abol¬ ishing the automatic movements (Fig 3). The slow-wave rhythm was never com¬ pletely desynchronized, however, and with¬ in eight minutes of the diazepam infusion it had increased in amplitude and frequen¬ cy again to 50µ and 4 Hz as the stereo¬ typed extremity, ocular and prosopoglossopharyngeal movements returned. Subse¬ quently, the synchronous arm jerks reap¬ peared and increased in frequency, culmi¬ nating in two clonic seizures. Phenytoin therapy, administered intravenously, was begun at 50 mg/hr, and no further clinical seizure activity was noted. By this time, phencyclidine was detected in urine, and a serum phencyclidine concentration of 0Mpg/m\ was subsequently determined. Thirty-six hours after admission, the patient remained stuporous, responding only to trachéal suctioning. Intermittent vertical nystagmus was still present, but the periodic motor manifestations were absent. There was still sustained cataleptic posturing of the extremities in virtually any position into which they were passively moved. Spontaneous semipurposeful move¬ ments occurred continually, unmodified by stimulation, but deep pain resulted in decorticate posturing. The EEG at this time showed continuous generalized sinu¬ soidal 30µ to 50µ , 7.5 Hz activity, maximal posteriorly, which remained unreactive to eye-opening, but desynchro-
2).
eight minutes after diazepam
;
spontaneous
movements
return
^v^sVuv/v\AA"VA/V four minutes
following diazepam; unresponsive,
no
movements
immediately following intravenous infusion of 10 mg. diazepam
over
2 min.
completely unresponsive but with spontaneous movement
Fig 3.—Diazepam-induced slowing and desynchronization of monorhythmic theta activity associated with disappearance of spontaneous stereotyped movements. Resynchronization and acceleration of slow-wave rhythm began about eight minutes later accompanied by reappearance of motor automatisms. Each of four samples consists of vertically compressed power spectra from nine successive four-second epochs of primary EEG data. Power is proportional to peak heights and is expressed with 0.25 Hz resolution. A representative four-second epoch of primary EEG data is plotted to right of each spectral block; slight irregularities in latter tracings are artifacts of computer analysis. Parieto-occipital EEG derivation. nized in response to trachéal suction. Forty hours after admission, the patient was extubated, and eight hours later he regained consciousness (appropriate verbal responsiveness). Seventy-two hours after admission, neurologic recovery was com¬ plete, and the EEG had returned to within normal limits, with a symmetric, reactive 8.5-Hz alpha rhythm. The patient stated
thing he remembered prior to awakening on the third hospital day was inhaling a large amount of "angel dust" on the night of admission. that the last
COMMENT
Rhythmic slowing of EEG back¬ ground activity has been reported in human volunteers receiving 0.1 to 0.3
Downloaded From: http://archneur.jamanetwork.com/ by a University of California - San Diego User on 06/05/2015
mg/kg phencyclidine hydrochloride intravenously,117'1'1 but the periodic EEG events seen early in this case were not observed in the experimental studies. The EEG and neurologic manifestations produced experimen¬ tally by 0.1 to 0.3 mg/kg phencyclidine hydrochloride given intravenously did
resemble those seen 36 hours after admission in our patient, at which time the serum concentration had presumably fallen well below the
earlier value. In one experimental human study,1 intravenous doses of 0.5 to 1.0 mg/kg phencyclidine hy¬ drochloride induced seizures, but the EEG effects were not reported. The EEG pattern of deep phency¬ clidine obtundation (Fig 1 and 2) is sufficiently specific to be of diag¬ nostic importance and, in fact, ini¬ tially suggested the diagnosis in the case presented; we had observed a similar pattern before only in patients deeply anesthetized with ketamine, a derivative of phencyclidine. Like their parent compound, ketamine (2-[orthochlorophenyl] 2- [methylamino] cyclohexanone) and other cyclohexylamine derivatives can produce rhythmic the¬ ta activity, which, at higher doses, is interrupted by periodic slow- or sharpwave complexes.171* Ketamine pro¬ duces a "cataleptoid" state of unre-
sponsiveness similar to that induced by phencyclidine and is gaining popu¬ larity as a street hallucinogen."> -" Thus, an electroclinical presentation similar to that described above might also be anticipated with ketamine intoxication.
This investigation was supported in part by an Epilepsy Foundation of American fellowship (Dr Stockard), and by US Public Health Service grant NS 08962. Kenneth R. Hanson assisted in the computer analysis of the EEG data. Susan Sampson and Gina Dronet aided in the preparation of the manuscript. R. G. Bickford, MB, FRCP, supplied recording and computing equipment.
Nonproprietary Name and Trademark of Drug
Phencyclidine hydrochloride-Serwî/ton. References 1. Greifenstein FE, DeVault M, Yoshitaki J, et al: A study of l-aryl cyclohexyl amine for anesthesia. Anesth Analg 37:283-294, 1958. 2. Johnstone M, Evans V, Baigel S: Sernyl (C1395) in clinical anesthesia. Br J Anesth 31:433\x=req-\ 439, 1959. 3. Luby ED, Cohen BD, Rosenbaum G, et al: Study of a new schizophrenomimetic drug\p=m-\ Sernyl. Arch Neurol Psychiatry 81:363-369, 1959. 4. Rainey JM, Crowder MK: Prevalence of phencyclidine in street drug preparations. N Engl J Med 290:466-467, 1974. 5. Rainey JM, Crowder MK: Ketamine or
phencyclidine. JAMA 230:824, 1974. 6. The perils of PCP. Drug Enforcement 1:8-9, 1974.
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