H O R T R E P O R T Cortical Blindness and Cerebral Infarction Associated With Severe Hypoglycemia dence of seizure activity for which she received phenytoin. An electroencephalogram (EEG) performed at this time showed almost continuous sharp wave discharges originating from the right parietal region; episodes of facial OBJECTIVE — To describe a case of cortical blindness and cerebral infarction associated with twitching were accompanied by an insevere hypoglycemia. crease in this sharp wave activity. In summary, the EEG revealed evidence of CONCLUSIONS — The possible pathogenesis of the neurological defects is discussed. severe cerebral insult. Over the next week, the patient showed some evidence of improvement ypoglycemia is a common compli- with most HbAlc concentrations in the and no longer required ventilation. There cation of insulin-treated diabetes. range 8.0-10.2% (normal range <6.0%). was evidence of spontaneous eye opening Recurrent severe hypoglycemia is She had no further episodes of severe hy- and some vocal noises. After 3 weeks, all associated with cognitive dysfunction poglycemia, and awareness of hypoglyce- seizure activity appeared to have resolved. (1,2) or even death (3). Other neurologi- mia appeared satisfactory. Over the next 4 weeks, there was a further cal manifestations of hypoglycemia inIn May 1995, the patient was ad- slow improvement in neurological funcclude hemiplegia, decerebration, ataxia, mitted with mild ketoacidosis, secondary tion. The patient moved all limbs spontachoreoathetosis, the "locked-in" syn- to a urinary tract infection. The most reneously and made spontaneous sounds. drome, and severe amnesia (4,5). Of re- cent HbAlc was 10.2%. On admission, Swallowing returned to normal. The paports on neurological manifestations of she was taking 100 Ul/day (1.3 U/kg). tient would turn to verbal stimuli but did nonfatal hypoglycemia, 50% are of tran- Following standard treatment, the patient not respond to visual stimuli. Fundussient abnormalities (4). made a rapid recovery. Marked reduc- copy and pupillary reflexes were normal. A severe hypoglycemic coma case tions in insulin doses were required so Visual evoked potentials revealed normal in a 22-year-old woman, resulting in per- that at the time of discharge, the patient electroretinograms, suggesting normal manent neurological abnormalities in- was taking a total daily dose of 74 U, and retinal function; however, the cortical recluding cortical blindness, is described. further reductions were made over the sponses recorded from either eye after a following few days. visual stimulus were grossly abnormal, Five days later, the patient was suggesting severe lesions within both corCASE— This 22-year-old woman developed diabetes at the age of 12. Glyce- found comatose in the morning by her tical areas of the visual system. A repeat mic control had never been particularly parents and was admitted to hospital. On EEG was reported as showing diffuse slow tight, but despite this, the patient had had the day before admission, she experi- wave activity but no seizure activity. a tendency to hypoglycemia, especially enced difficulty in avoiding hypoglyceTwo months after admission, the related to sports. Between 1989 and mia, despite taking extra carbohydrate patient was able to walk if guided and eat 1991, the patient experienced three epi- and further reducing the insulin doses. with assistance but was unable to talk cosodes of severe hypoglycemia requiring There had been no strange behavior, and herently or understand basic verbal comglucagon. In June 1991, she was found by there appeared to be no suicidal motivamands. Four months after admission, the tion. On admission to the hospital, the her parents unconscious in bed and profoundly hypoglycemic, and on this ad- patient exhibited decerebrate move- CT scan was repeated (Fig. IB). There mission she required ventilation. Com- ments. Blood glucose was < 1 mmol/1. were marked changes compared with the puted tomography (CT) scan showed no Emergency CT scan (Fig. 1A) showed no scan performed on admission, with eviabnormality. The patient made an appar- abnormality, and a lumbar puncture was dence of gross global cerebral atrophy ent full recovery of neurological function normal. Cortisol response to tetracosactin with areas of attenuation in the posterior and was discharged home. was satisfactory. Over the next 4 days, the parietal regions consistent with possible Over the next 4 years, the patient's patient experienced apneic episodes re- infarction. EEG activity had not changed. The patient remained entirely deglycemic control remained suboptimal, quiring ventilation, and there was evipendent and required constant supervision. The parents wished to manage their daughter at home. However, the availabilI;rom the Department of Diabetes, Newcastle General Hospital, Newcastle upon Tyne, U.K. ity of financial support for providing apAddress correspondence and reprint requests to A.E. Gold, MD, Ward 3 Office, Newcastle General propriate assistance was not forthcoming. Hospital, Westgate Rd., Newcastle upon Tyne NE4 6BE, U.K. The patient's mother has given up her Received for publication 22 January 1996 and accepted in revised form 2 May 1996. work to care for her daughter. CT, computed tomography; EEG, electroencephalogram; MR1, magnetic resonance imaging. ANN E. GOLD, MD SALLY M. MARSHALL, MD H DIABETES CARE, VOLUME 19, NUMBER 9, SEPTEMBER 1996 1001 Cortical blindness and hypoglycemia B Figure 1—A: CT scan without contrast 12 h after admission with severe hypoglycemia B: CT scan taken 4 months after admission with severe hypoglycemia. 1002 C O N C L U S I O N S — This case history illustrates the devastating effect that a single episode of severe hypoglycemia may have on a patient and his or her family. The cerebral damage sustained included gross cerebral atrophy and probable cerebral infarction, which were manifest as severe cognitive changes and as cortical blindness, which was confirmed clinically and on evoked potential recordings. Cortical blindness is defined as the loss of vision in the presence of normal pupillary reflexes and in the absence of ophthalmological disease. Transient cortical blindness has previously been documented as a result of hypoglycemia in a child with a glycogen storage disease (6), but to our knowledge, permanent cortical blindness as a result of hypoglycemia has not been described in a patient with insulin-treated diabetes. Postictal cortical blindness has been described both in adults and in children (7-10). In almost all of these cases, the defect was transient. It has been suggested that, particularly in children, there is an increased susceptibility of the occipital cortex to paroxysmal EEG abnormalities, which appear to migrate towards the temporal regions as children grow older (9). Other cerebral insults have also been associated with cortical blindness: hypoxia, cardiac arrest, trauma, intracranial hemorrhage, X-ray contrast media, and hyponatremia (11-15). The occipital cortex receives its blood supply from both middle and posterior cerebral arteries. If one vessel is occluded, this dual blood supply protects the area from ischemic damage, but if there is general hypoxia, for example during prolonged hypotension, this protection does not occur (15). A recent pilot study examined the effects of the postanoxic syndrome on cerebral glucose metabolism in patients who had suffered a cardiac arrest (16). Using positron emission tomography, regional decreases in cerebral glucose metabolism were demonstrated, particularly in the parietal and occipital cortices, and were associated with cortical blindness. The authors suggest that cerebral hypoxia induces hypometabolism, which preferentially affects regions in arterial border zones (16). Acute hypoglycemia induces changes in homeostasis and coagulation defects (17). Increases in von Willebrand factor during acute hypoglycemia may promote platelet adhesion, and changes DIABETES CARE, VOLUME 19, NUMBER 9, SEPTEMBER 1996 Gold and Marshall hyponatremia: dynamic cerebral dysfuncin fibrinolysis may result in a hypercoaguReferences tion visualised using serial SPECT scan lablc state (17). An imbalance between rung. J Xm-I Mi-d to 127,1--1274. UWfi coagulation and fibrinolysis, with coagu1. Wrcdling R, Levander S, AdamsonU, Lins 14. Weinberger HA, van der YVoudc R, Maicr lation predominant, has been demonPE: Permanent neuropsychological imHC: Prognosis of cortical blindness folstrated during acute hypoglycemia (18). pairment after recurrent episodes of selowing cardiac arrest in children. jAM\ Such changes may predispose to thromvere hypoglycaemia in man. Diabetologia 179:126-129, 1%2 33:152-157, 1990 bosis and precipitate cerebral infarction, 2. Langan SJ, Deary IJ, Hepburn DA, Frier 15. Sabah AH: Blindness after cardiac arrest. as was suggested by the CT scan in the Postgraduate MedJ 44:51 \ -516, 1 % 8 BM: Cumulative cognitive impairment patient described. Although no specific 16. DeVoiderAG, Michel C, Guerit )M, Bol A, following recurrent severe hypoglycaemia changes were demonstrated on CT or Georges B, de Barsy T, l.atene C: Brain in adult patients with insulin-treated diaV.V.G in the occipital regions, which may glucose metabolism in posianoxic synbetes mellitus. Diabetologia 34:337-344, have been anticipated in cortical blinddrome due to cardiac arrest. Ada Xeutol 1991 ness, it is possible that the gross atrophic Belgica 94:183-189, 1994 3. Kalimo H, Olsson Y: Effects of severe hychanges may have masked more subtle poglycaemia on the human brain: neuro- 17. Fisher BM, Quin ]D, Rumley A, 1 ennie areas of infarction in this region. Tranpathological case reports. Ada Neurolo SE, Small M, MacCuish AC, Lowe GDO: sient cortical blindness in association Scand 62:345-356, 1980 Effects of acute insulin-induced Inpogk •• with other neurological conditions and 4. Lins P-E, Adamson U: Neurological mancaemia on haemosiasis, fibrinolysis, and potentially hypercoagulable states in nonifestations of hypoglycaemia. In Hypoglyhaemorheology in insulin-dependent dicaemia and Diabetes: Clinical and Physisodiabetic patients has been demonstrated abetic patients and control subjects, Clin logical Aspects. Frier BM, Fisher BM, Eds. to be associated with abnormalities on Sri 80:525-531, 1991 London, Edward Arnold, 1993, p. 347- 18. Wieczorek 1, Pell ACH, Mclver B, magnetic resonance imaging (MRI) and 354 (IT scans, which may have been secondMacGregor IR, Ludlam CA, Frier BM: Co 5. ChalmersJ, RiskMTA, KeanDM, Grant R, ary to small cortical venous thromboses agulation and fibrinolytic systems in typo Ashworth B, Campbell IW: Severe amne1 diabetes: effects of venous occlusion and (1°-). in addition, MRI may identify some sia after hypoglycemia. Diabetes Care 14: insulin-induced hypoglycaemia. Clin .s\i occipital lesions that are not visible on CT 922-925, 1991 84:79-86, 1993 scanning (19). It is possible that the ap6. Mukamel M, Weitz R, Nissenkorn 1, Yas19. Patronas NJ, Argyropoulou M: lntravas ncic and convulsive episodes experienced sur I, Varsano I: Acute cortical blindness cular thrombosis as a possible cause of by the patient contributed to the cerebral associated with hypoglycemia. ] Pediatr transient cortical brain lesions: CT and changes; however, these episodes oc98:583-584, 1981 MRI. J Computer Assisted Tomography 16: curred while the patient was being venti7. Barnet AB, Manson Jl, Wilner E: Acute 84Q-855, 1992 lated, and no significant prolonged detecerebral blindness in childhood. Neurol20. Gold AE, Deary II, Jones RW, O'Hare ]I\ ogy 20:1147-1152,1970 riorations in oxygen saturation were 8. Kosnik E, Paulson GW, Laguna JF: PosReckless JPD, F'rier BM: Severe deteriorapermitted. tictal blindness. Neurology 26:248-250, tion in cognitive function and personal This case also illustrates the diffi1976 ity in five patients with long-standing culty faced by caregivers of patients with 9. Zung A, Margalith D: Ictal cortical blinddiabetes: a complication of diabetes or a cerebral dysfunction (20) and the lack of ness: a case report and review of the literconsequence of treatment? Diabetic Med facilities and resources to meet their ature. Dev Med Child Neurol 35:917-926, 11:499-505, 1994 needs. 1993 21. Heller SR, Cryer PE: Reduced neuroendo • The cause of the hypoglycemia in 10. JosephJM, Louis S: Transient ictal cortical crine and symptomatic responses to subblindness during middle age: a case report this patient remains unknown. It is possisequent hypoglycemia after one episode and review of the literature. J Neuro Ophble that the ability of the patient to counof hypoglycemia in nondiabetic humans. thal 15:39-42, 1995 terregulate was impaired because of the Diabetes 40:223-226, 1991 frequent episodes of hypoglycemia expe- 11. Wong VC: Cortical blindness in children: 22. Dagogo-Jack SE, Craft S, Cryer PE: 1 lypo a study of etiology and prognosis. Pediatr rienced the previous day (21,22), thereby glycemia-associated autonomic failure Neurol 7:178-185, 1991 predisposing the patient to severe hypoin insulin-dependent diabetes mellitus: 12. Kermode AG, Chakera T, Mastaglia FL: glycemia. In conclusion, cerebral infarcrecent antecedent hypoglycemia reLow osmolar and non-ionic X-ray contion and cortical blindness are rare comduces autonomic responses to, symptrast media and cortical blindness. Clin plications of severe hypoglycemia but toms of, and defense against subsequent Exp Neurol 29:272-276, 1992. hypoglycemia. / Clin Invest 91:819-8/>8, have a profound effect on rehabilitation 13. Hagerty C, Licho R, Recht L: Cortical blin1993 and quality of life. deness after correction of symptomatic 1)IAFH:TE:S CARE, VOLUME 19, NUMBER 9, SEPTEMBER 1996 1003