Delayed Hypoxic Encephalopathy Without Cognitive Dysfunction LCDR Michael W. Devereaux, MC, USNR, Michael J. Partnow, MD
\s=b\ Three days after an episode of hypoxia, a 20-year-old man developed profound motor deficit in the absence of behavioral or cognitive disturbance. Previous reviews of delayed hypoxic encephalopathy have stressed behavioral and cognitive disturbances as the initial symptoms. This patient's pyramidal tract dysfunction in the absence of higher cortical dysfunction serves to illustrate that delayed hypoxic encephalopathy is predominantly a white matter rather than a
gray matter disorder. (Arch Neurol 32:704-705, 1975)
delayed encephalopa¬ Asyndrome thy following hypoxia of
of varied cause has been described in the litera¬ ture. Carbon monoxide poisoning,16 anoxic anoxia,s surgical complica¬ tions,4 578 cardiac arrest," and heroin overdose9 have all been associated with initial transient recovery lasting for a period of hours4 to weeks2 fol¬ lowed by neurologic deterioration. Virtually all of the patients described
for publication Jan 7, 1975. From the Section of Neurology, Department of Medicine, Navy Regional Medical Center, Philadelphia, the Division of Neurology, Hahnemann Medical College, Philadelphia, and the departments of neurology of Rancocas Valley Hospital, Willingboro, NJ, and the University of
Accepted
Pennsylvania. Reprint requests to Department of Neurology, Rancocas Valley Hospital, Willingboro, NJ 08046 (Dr. Partnow).
presented with cognitive or behav¬ ioral changes or both after a lucid in¬ terval; frequently the initial impres¬ sion was psychiatric illness.
The purpose of this communication is to describe another patient with this uncommon condition who, unlike
others, developed profound
motor
deficit in the absence of behavioral cognitive disturbance.
or
REPORT OF A CASE A 20-year-old man underwent extraction of impacted wisdom teeth. Several hours later blood was oozing from the surgical site. In preparation for ligation of a lacer¬ ated lingual artery, succinylcholine was administered, and trachéal intubation was performed with great difficulty. The pa¬ tient was hypoxic for about five minutes. He awoke from anesthesia and appeared well. Because of the hypoxic episode, neu¬ rologic consultation was requested 15 hours postoperatively. At that time the pa¬ tient was awake, alert, and able to follow complex commands, but unable to speak because of the oral packing and a tracheostomy. He could write well and by this method his general fund of knowledge, memory, judgment, and ability to perform mathetmatical computations were found to be normal. His general behavior and mood were appropriate. He displayed general¬ ized hyperreflexia with Babinski sign pres¬ ent bilaterally. The remainder of the neu¬ rologic examination gave normal results.
Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/09/2015
In the first 72 hours after surgery the
patient was ambulatory. The tracheostomy was closed and speech was found to be nor¬ mal. On the third postoperative day he de¬ veloped "spastic movements" of the right hand and began to have difficulty walking. During the next several hours his symp¬ toms progressed and he experienced diffi¬ culty with micturition. Neurologic examination revealed his mental status, language function, cranial nerves, sensation, and anal sphincter to be normal. He was quadriparetic with hyperreflexia (4 + ) and Babinski sign present bi¬ laterally. He had periodic 4 to 5 cps myo¬ clonic movements involving all extremities
in various combinations. An EEG showed bitemporal theta slowing. There was no paroxysmal activity related to the extrem¬
ity movements. By the fourth postoperative day the
pa¬ tient was mute but able to communicate by eye blink. He could grimace and open his mouth to commands. He had right-gaze preference, easily overcome by the oculocephalic reflex. The patient also had facial diparesis, inability to protrude his tongue, quadriplegia with increased extensor tone in all extremities, and hyperreflexia (4 + ) with Babinski sign present bilaterally. In addition he had a hyperactive jaw jerk (3 + ). Skull and cervical spine roentgen¬ ograms, lumbar puncture, and cerebral an¬ giography were done with normal results. By the tenth postoperative day the pa¬ tient would no longer follow commands, and persistent grimacing and chewing movements resulted in maceration of his
lip. On the 13th postoperative day he spontaneously looking in all fields of gaze. From this day he gradually began to improve. He started to follow verbal com¬ mands again and to take fluids orally. By the 49th postoperative day he was speaking in simple phrases although he had a pronounced dysarthria. By the 79th postoperative day he could answer all questions verbally. On the 104th postoperative day a Wechs¬ ler Adult Intelligence Scale verbal subtest showed an IQ of 88. His naval entrance test (general classification test) had shown an IQ of 97. The most recent examination again lower was
showed his mental status to be normal. He has continued to have pseudobulbar dys¬ arthria and severe spastic quadriparesis. He remembers almost everything that happened during his illness, even those pe¬ riods when it appeared that he was unable to communicate or follow commands. He was able to describe his angiogram in de¬ tail. He remembered macerating his lips for several days and commented that he was unable to control the chewing move¬ ments. He claimed that he stopped commu¬ nicating by eye blink because he was tired of cooperating and wanted to be left alone.
COMMENT
Although acute neurologic dysfunc¬ hypoxia is well recognized, delayed neurologic deterioration af¬ tion from
ter a normal interval is not. The syn¬ drome is discussed in detail by Plum et al5 in 1962 with initial descriptions dating to 1891.' The disorder most
commonly has followed carbon mon¬ oxide poisoning, probably because of the ubiquity of this gas and its ability to cause prolonged sublethal anoxia.5-6
The associated pathological changes have been characteristic.2·35710 In
hypoxic encephalopathy, primarily found in gray matter while in delayed hypoxic en¬ cephalopathy there is demyelination with relative sparing of neurons. Pos¬ sible mechanisms resulting in demye¬ lination include hypoxic-induced dam¬ acute
changes
are
age to small blood vessels, cerebral edema, and encephalomyelitis. Plum et al5 explored each mechanism in de¬ tail and found all unsatisfactory as causal explanations. Bass10 studied the brains of animals with cyanideinduced hypoxic encephalopathy known to produce a pathological pic¬ ture similar to that seen in delayed hypoxia. He noted the selective de¬ struction of oligodendroglia followed by the breakdown of myelin mem¬ branes with preservation of neurons. He suggested that a similar distur¬ bance of the oligodendroglia myelin membrane system might account for
the
demyelination seen with delayed hypoxic encephalopathy. Our patient differs from those pre¬ viously described in that he presented with progressive spastic quadripa¬ resis without evidence of cognitive or
behavioral disorder. Mental status ex¬ aminations, repeated until brain stem dysfunction made such testing diffi¬ cult, showed no abnormalities. Psychometric examination several months after the neurologic insult demonstrated an IQ only slightly lower than his premorbid IQ. It is of interest that his memory was intact for the period in which he had severe
Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/09/2015
neurologie dysfunction. He was able during that time in great detail, lending credence to his claim that he did not respond to at¬ to describe events
at communication via eye blink because of a desire to be left alone rather than because of cogni¬ tive dysfunction. The patient's severe spastic quad¬ riparesis in the face of little or no cognitive deterioration is consistent with the finding that delayed hypoxic encephalopathy is the result of white matter disease with relative sparing of the cerebral cortex.
tempts
References 1. Cramer A: Anatomischer Befund im Gehirn bei einer Kohlenoxydgasvergiftung. Zentrabl Allg Pathol 2:545-550, 1891. 2. Courville CB: The process of demyelination in the central nervous system. J Nerv Ment Dis 125:534-546, 1957. 3. Schwedenberg TH: Leukoencephalopathy following carbon monoxide asphyxia. J Neuropathol Exp Neurol 18:597-608, 1959. 4. Richardson JC, Chambers RA, Heywood PM: Encephalopathies of anoxia and hypoglycemia. Arch Neurol 1:178-190, 1959. 5. Plum F, Posner JB, Hain RF: Delayed neurological deterioration after anoxia. Arch Intern Med 110:56-63, 1962. 6. Brucher JM: Neuropathological problems posed by carbon monoxide poisoning and anoxia. Prog Brain Res 24:75-100, 1967. 7. Abbott CN, Courville CB: Degeneration of the globus pallidus after nitrous oxide anesthesia. Bull Los Angeles Neurol Soc 3:46-50, 1938. 8. Gebauer PW, Coleman FP: Postanesthetic encephalopathy following cyclopropane. Ann Surg 107:481-485, 1938. 9. Protass LM: Delayed postanoxic encephalopathy after heroin use. Ann Intern Med 74:738\x=req-\ 739, 1971. 10. Bass NH: Pathogenesis of myelin lesions in experimental cyanide encephalopathy. Neu-
rology 18:167-177,
1968.
\s=b\ Three days after an episode of hypoxia, a 20-year-old man developed profound motor deficit in the absence of behavioral or cognitive disturbance. Previous reviews of delayed hypoxic encephalopathy have stressed behavioral and cognitive disturbances as the initial symptoms. This patient's pyramidal tract dysfunction in the absence of higher cortical dysfunction serves to illustrate that delayed hypoxic encephalopathy is predominantly a white matter rather than a
gray matter disorder. (Arch Neurol 32:704-705, 1975)
delayed encephalopa¬ Asyndrome thy following hypoxia of
of varied cause has been described in the litera¬ ture. Carbon monoxide poisoning,16 anoxic anoxia,s surgical complica¬ tions,4 578 cardiac arrest," and heroin overdose9 have all been associated with initial transient recovery lasting for a period of hours4 to weeks2 fol¬ lowed by neurologic deterioration. Virtually all of the patients described
for publication Jan 7, 1975. From the Section of Neurology, Department of Medicine, Navy Regional Medical Center, Philadelphia, the Division of Neurology, Hahnemann Medical College, Philadelphia, and the departments of neurology of Rancocas Valley Hospital, Willingboro, NJ, and the University of
Accepted
Pennsylvania. Reprint requests to Department of Neurology, Rancocas Valley Hospital, Willingboro, NJ 08046 (Dr. Partnow).
presented with cognitive or behav¬ ioral changes or both after a lucid in¬ terval; frequently the initial impres¬ sion was psychiatric illness.
The purpose of this communication is to describe another patient with this uncommon condition who, unlike
others, developed profound
motor
deficit in the absence of behavioral cognitive disturbance.
or
REPORT OF A CASE A 20-year-old man underwent extraction of impacted wisdom teeth. Several hours later blood was oozing from the surgical site. In preparation for ligation of a lacer¬ ated lingual artery, succinylcholine was administered, and trachéal intubation was performed with great difficulty. The pa¬ tient was hypoxic for about five minutes. He awoke from anesthesia and appeared well. Because of the hypoxic episode, neu¬ rologic consultation was requested 15 hours postoperatively. At that time the pa¬ tient was awake, alert, and able to follow complex commands, but unable to speak because of the oral packing and a tracheostomy. He could write well and by this method his general fund of knowledge, memory, judgment, and ability to perform mathetmatical computations were found to be normal. His general behavior and mood were appropriate. He displayed general¬ ized hyperreflexia with Babinski sign pres¬ ent bilaterally. The remainder of the neu¬ rologic examination gave normal results.
Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/09/2015
In the first 72 hours after surgery the
patient was ambulatory. The tracheostomy was closed and speech was found to be nor¬ mal. On the third postoperative day he de¬ veloped "spastic movements" of the right hand and began to have difficulty walking. During the next several hours his symp¬ toms progressed and he experienced diffi¬ culty with micturition. Neurologic examination revealed his mental status, language function, cranial nerves, sensation, and anal sphincter to be normal. He was quadriparetic with hyperreflexia (4 + ) and Babinski sign present bi¬ laterally. He had periodic 4 to 5 cps myo¬ clonic movements involving all extremities
in various combinations. An EEG showed bitemporal theta slowing. There was no paroxysmal activity related to the extrem¬
ity movements. By the fourth postoperative day the
pa¬ tient was mute but able to communicate by eye blink. He could grimace and open his mouth to commands. He had right-gaze preference, easily overcome by the oculocephalic reflex. The patient also had facial diparesis, inability to protrude his tongue, quadriplegia with increased extensor tone in all extremities, and hyperreflexia (4 + ) with Babinski sign present bilaterally. In addition he had a hyperactive jaw jerk (3 + ). Skull and cervical spine roentgen¬ ograms, lumbar puncture, and cerebral an¬ giography were done with normal results. By the tenth postoperative day the pa¬ tient would no longer follow commands, and persistent grimacing and chewing movements resulted in maceration of his
lip. On the 13th postoperative day he spontaneously looking in all fields of gaze. From this day he gradually began to improve. He started to follow verbal com¬ mands again and to take fluids orally. By the 49th postoperative day he was speaking in simple phrases although he had a pronounced dysarthria. By the 79th postoperative day he could answer all questions verbally. On the 104th postoperative day a Wechs¬ ler Adult Intelligence Scale verbal subtest showed an IQ of 88. His naval entrance test (general classification test) had shown an IQ of 97. The most recent examination again lower was
showed his mental status to be normal. He has continued to have pseudobulbar dys¬ arthria and severe spastic quadriparesis. He remembers almost everything that happened during his illness, even those pe¬ riods when it appeared that he was unable to communicate or follow commands. He was able to describe his angiogram in de¬ tail. He remembered macerating his lips for several days and commented that he was unable to control the chewing move¬ ments. He claimed that he stopped commu¬ nicating by eye blink because he was tired of cooperating and wanted to be left alone.
COMMENT
Although acute neurologic dysfunc¬ hypoxia is well recognized, delayed neurologic deterioration af¬ tion from
ter a normal interval is not. The syn¬ drome is discussed in detail by Plum et al5 in 1962 with initial descriptions dating to 1891.' The disorder most
commonly has followed carbon mon¬ oxide poisoning, probably because of the ubiquity of this gas and its ability to cause prolonged sublethal anoxia.5-6
The associated pathological changes have been characteristic.2·35710 In
hypoxic encephalopathy, primarily found in gray matter while in delayed hypoxic en¬ cephalopathy there is demyelination with relative sparing of neurons. Pos¬ sible mechanisms resulting in demye¬ lination include hypoxic-induced dam¬ acute
changes
are
age to small blood vessels, cerebral edema, and encephalomyelitis. Plum et al5 explored each mechanism in de¬ tail and found all unsatisfactory as causal explanations. Bass10 studied the brains of animals with cyanideinduced hypoxic encephalopathy known to produce a pathological pic¬ ture similar to that seen in delayed hypoxia. He noted the selective de¬ struction of oligodendroglia followed by the breakdown of myelin mem¬ branes with preservation of neurons. He suggested that a similar distur¬ bance of the oligodendroglia myelin membrane system might account for
the
demyelination seen with delayed hypoxic encephalopathy. Our patient differs from those pre¬ viously described in that he presented with progressive spastic quadripa¬ resis without evidence of cognitive or
behavioral disorder. Mental status ex¬ aminations, repeated until brain stem dysfunction made such testing diffi¬ cult, showed no abnormalities. Psychometric examination several months after the neurologic insult demonstrated an IQ only slightly lower than his premorbid IQ. It is of interest that his memory was intact for the period in which he had severe
Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/09/2015
neurologie dysfunction. He was able during that time in great detail, lending credence to his claim that he did not respond to at¬ to describe events
at communication via eye blink because of a desire to be left alone rather than because of cogni¬ tive dysfunction. The patient's severe spastic quad¬ riparesis in the face of little or no cognitive deterioration is consistent with the finding that delayed hypoxic encephalopathy is the result of white matter disease with relative sparing of the cerebral cortex.
tempts
References 1. Cramer A: Anatomischer Befund im Gehirn bei einer Kohlenoxydgasvergiftung. Zentrabl Allg Pathol 2:545-550, 1891. 2. Courville CB: The process of demyelination in the central nervous system. J Nerv Ment Dis 125:534-546, 1957. 3. Schwedenberg TH: Leukoencephalopathy following carbon monoxide asphyxia. J Neuropathol Exp Neurol 18:597-608, 1959. 4. Richardson JC, Chambers RA, Heywood PM: Encephalopathies of anoxia and hypoglycemia. Arch Neurol 1:178-190, 1959. 5. Plum F, Posner JB, Hain RF: Delayed neurological deterioration after anoxia. Arch Intern Med 110:56-63, 1962. 6. Brucher JM: Neuropathological problems posed by carbon monoxide poisoning and anoxia. Prog Brain Res 24:75-100, 1967. 7. Abbott CN, Courville CB: Degeneration of the globus pallidus after nitrous oxide anesthesia. Bull Los Angeles Neurol Soc 3:46-50, 1938. 8. Gebauer PW, Coleman FP: Postanesthetic encephalopathy following cyclopropane. Ann Surg 107:481-485, 1938. 9. Protass LM: Delayed postanoxic encephalopathy after heroin use. Ann Intern Med 74:738\x=req-\ 739, 1971. 10. Bass NH: Pathogenesis of myelin lesions in experimental cyanide encephalopathy. Neu-
rology 18:167-177,
1968.
