149
15
Toxic and Metabolic Disorders
WERNICKE-KORSAKOFFSYNDROME 149 DELIRIUMTREMENS 150
TOXEMIA OFPREGNANCY 150
Wernicke-Korsakoff Syndrome
Vignette
A 68-year-old man was found by the police wan- dering at the airport confused, disheveled, and ac- tively confabulating. In the emergency room, he seemed malnourished and had low-grade fever. He knew his name, but could not tell the date or place.
He could not remember three items after five min- utes. He did not recall his birthday or his mother’s name. He identified the patient in the next bed as his father and seemed to recognize people whom he never saw before. On examination, he had normally reactive pupils. On attempted lateral gaze to each side, the adducting eye moved only a few degrees medial to the midline. There was a coarse nystag- mus of the abducting eye. Motor and sensory ex- aminations were normal. Ankle jerks were absent bilaterally. Gait was wide-based ataxic.
Summary A 68-year-old man disoriented, confused, hal- lucinating, with both anterograde and retrograde amnesia, bilateral internuclear ophthalmoplegia, absent ankle jerks, and ataxic gait.
Localization
Confusion is attributed to bilateral cerebral dysfunction.
The amnestic disorder may localize to lesions affecting the diencephalon and mesencephalon, particularly the medial dorsal nucleus of the thalamus and the hippocam- pal formation (Adams and Victor).
Differential Diagnosis
The first consideration among the clinical features de- scribed in the vignette is the severe amnestic syndrome
with confabulations. The differential diagnosis includes several categories, but the patient found confused with severe memory loss and typical neurological findings could represent a clear example of the Wernicke- Korsakoff syndrome, which is due to thiamine deficiency.
The causes include primarily chronic alcohol abuse but also severe vomiting, gastric and other malignancy, and chronic systemic disorders.
In the differential diagnosis of the case presented, con- sideration also needs to be given to other etiologies:
• Vascular disorders, such as bilateral posterior cerebral artery CVA that can manifest with severe amnesia, ag- itation, and delirium but also cortical blindness.
• Infections, such as herpes encephalitis, that cause acute mental status changes and hallucinations.
• Paraneoplastic limbic encephalitis.
Clinical Features
Wernicke’s disease is characterized by typical neurolog- ical findings that include nystagmus, ophthalmoplegia, imbalanced gait with ataxia, and mental status changes.
Korsakoff psychosis is defined by Adams and Victor as an abnormal mental state in which memory and learning are affected out of proportion to other cognitive functions in an otherwise alert and responsive patient.
Ocular abnormalities include nystagmus, which can be horizontal and vertical, and ophthalmoplegia that in- volves the abducens nerve with bilateral lateral rectus pa- ralysis. Conjugate gaze paralysis, particularly horizontal, ptosis, and internuclear ophthalmoplegia are other ocular findings described in patients with Wernicke’s syndrome.
Unsteady gait with ataxia of varying degree of severity is also commonly found, as well as signs of peripheral nerve dysfunction such as pain, paresthesias, and reflex and sensory loss.
Mental status changes present in Wernicke’s encepha- lopathy include apathy, drowsiness, inattention, confu- sion, stupor, and so on. Korsakoff’s amnestic syndrome
150 15. Toxic and Metabolic Disorders
that can represent the initial manifestation of WKS is characterized by prominent retrograde and anterograde amnesia (the latter more severe) which in some patients is associated with confabulations. The diagnosis of Kor- sakoff’s amnestic state also includes other aspects of mental functions, such as an alert and responsive patient who is aware of his or her surroundigs and does not show an inappropriate social behavior (Adams and Victor).
The hallmarks of the disorder are
• Retrograde amnesia: Inability to recall events and other information that had been acquired over a period of many months or years before the onset of the illness.
• Anterograde amnesia: Inability to secure new infor- mation by learning or forming new memories.
• Confabulations: Falsifications of memory. Patients tend to fill in blanks in their memory with material that they fabricate.
Delirium Tremens
Vignette
A 55-year-old construction worker became con- fused two days after undergoing total right knee replacement. The neurology resident called by a concerned orthopedic attending noticed that the patient was agitated and uncooperative and he was pointing around the room as if he was seeing people or objects that were not present. He was tremulous and tachycardic. Otherwise the neurological ex- amination was not focal.
Summary A 55-year-old man with changes in mental status two days after undergoing surgery for right knee replacement.
Differential Diagnosis, Diagnosis, and Treatment
Several syndromes can be associated with delirium and acute confusional state, particularly in hospitalized pa- tients. These include systemic infections causing bacter- emia, septicemia, and pneumonia, or infections localized to the central nervous system, such as meningitis, en- cephalitis, and so on.
Metabolic and endocrine abnormalities are an impor- tant consideration, in particular hypo/hyperosmolality, hypo/hypernatremia, hypercalcemia, hypoglicemia, he- patic and uremic encephalopathy, and so on.
Other etiologies include trauma, particularly compli- cated by subdural hematoma, intracranial hemorrhages, transient ischemic attacks, hypertensive encephalopathy,
multiple emboli, and drug and alcohol intoxication and withdrawal.
Considering the case presented in the vignette, acute confusion with tremulousness and visual hallucinations beginning two days after admission to the hospital is highly suspicious of delirium tremens. Delirium tremens manifests acutely several days after alcohol withdrawal.
Typical symptoms include confusion, agitation, tremor, diaphoresis, insomnia, delusions, visual hallucinations, and marked sympathetic hyperactivity with hyperther- mia, tachycardia, pupillary dilatation, tremor, nausea, vomiting, diarrhea, profuse sweating, and so on.
Associated electrolyte abnormalities, hyperthermia, and dehydration with circulatory collapse can be fatal (Miles and Diamond). In the majority of cases, the epi- sode lasts less than 72 hours and resolves.
The treatment is based on the correction of fluid and electrolyte abnormalities. Withdrawal symptoms and ag- itation are treated with the use of benzodiazepines.
Toxemia of Pregnancy
Vignette
A 32-year-old female recent Pakistani immigrant started experiencing visual difficulties and became completely blind after a few hours. Her previous history was significant for 34 weeks of gestation and poor prenatal care. In the emergency room she appeared drowsy and was complaining of head- ache. Blood pressure was 150/100. Pupils were 3 mm and normally reactive. Funduscopic examina- tion was normal, with spontaneous venous pulsa- tion. She did not blink to threat. The rest of the neurological examination was normal.
Summary A 32-year-old woman 34 weeks pregnant, hy- pertensive, experiencing acute bilateral visual loss and drowsiness.
Localization
The localization points to a postchiasmatic lesion. The normal pupillary reactions and normal ophthalmoscopic findings are characteristic of cortical blindness.
Differential Diagnosis and Diagnosis
Several disorders can be associated with cortical blind- ness, such as vascular, infectious, toxic, metabolic, neu- rodegenerative, traumatic, and so on.
The patient described in the vignette is a pregnant woman with hypertension. This suggests the very impor- tant possibility of preeclampsia or eclampsia as a causa-
References 151
tive factor. Blindness can be a complication of severe preeclampsia and eclampsia and may last several days, rapidly resolving after delivery. The problem usually is caused by multiple microhemorrhages and microinfarcts occurring in the occipital lobe (Arias).
Cortical blindness can also be caused by vascular dis- orders involving the posterior circulation, in particular embolic or thrombotic occlusion of the posterior cerebral arteries or basilar artery.
Infectious processes include meningitis, encephalitis such as Creutzfeld-Jacob disease, AIDS, subacute scle- rosing panencephalitis, and so on.
Metabolic and toxic causes include hypoglycemia, ure- mia, carbon monoxide poisoning, mercury, ethanol intox- ication, and so on.
Degenerative causes of cortical blindness include met- achromatic leukodystrophy, Leigh’s disease, mitochon- drial disorders, and so on.
Finally, a transitory form of cortical blindness may be the consequence of head trauma, particularly in children.
Basilar migraine can also manifest with transitory cortical blindness.
Preeclampsia is characterized by hypertension, protein- uria, edema, and headache after 20 weeks of gestation.
Eclampsia is characterized by the occurrence of gener- alized tonic-clonic seizures in women with preeclampsia.
Eclampsia occurs antepartum in 46.3 percent, intrapartum in 16.4 percent, and postpartum in 37.3 percent of cases (Arias).
Visual hallucinations, usually streaks of light, often precede the onset of eclamptic convulsions (Donaldson in Devinsky et al.). Visual hallucinations and cortical blindness are due to involvement of the occipital area.
Other neurological signs include hyperreflexia and oc- casionally clonus.
The management includes magnesium sulfate for sei- zure prevention, control of severe hypertension, and fluid restriction to prevent worsening of cerebral edema.
References
Wernicke-Korsakoff Syndrome
Adams, R.D. and Victor, M. Principles of Neurology, ed. 5. New York: McGraw-Hill, 851–858, 1993.
Case Records of the Massachusetts General Hospital. Case 33.
N. Engl. J. Med. 503–508, 1986.
Miles, M.F. and Diamond, I. Neurological complications of al- coholism and alcohol abuse In: Aminoff, M.J. and Goetz, C.G. (Eds.). Handbook of Clinical Neurology, Vol. 26. New York: Elsevier, 339–365, 1998.
Victor, M. et al. The Wernicke-Korsakoff Syndrome. Philadel- phia: F.A. Davis, 1989.
Delirium Tremens
Adams, R.D. and Victor, M. Principles of Neurology, ed. 5. New York: McGraw-Hill, 912–915, 1993.
Miles, M. and Diamond, I. Neurological complications of al- coholism and alcohol abuse. In: Handbook of Clinical Neu- rology, Vol. 26. New York: Elsevier, 340–345, 1998.
Tasman, A. et al. Psychiatry, Vol. 1. Philadelphia: W.B. Saun- ders, 917–921, 1997.
Toxemia of Pregnancy
Arias, F. Practical Guide to High-Risk Pregnancy and Delivery, ed. 2. St. Louis: Mosby, 183–210, 1992.
Cunningham, F.G. et al. Blindness associated with preeclampsia and eclampsia Am. J. Obstet. Gynecol. 172:1291–1298, 1995.
Devinsky, O. et al. Neurological Complications of Pregnancy.
New York: Raven, 25–33, 1994.
Goodlin, R.C. et al. Cortical blindness as the initial symptom in severe preeclampsia. Am. J. Obstet. Gynecol. 147:841–
842, 1983.
Hinchey, J. et al. A reversible posterior leukoencephalopathy syndrome. N. Engl. J. Med. 334:494–500, 1996.
Rowland, L. Merritt’s Textbook of Neurology, ed. 8. Philadel- phia: Lea and Febiger, 896–897, 1989.
