the neurological manifestations complicated by profound hypoglycemia range from reversible focal deficits to irreversible coma ( 1 , 2 ) . and the brain - imaging abnormalities and their sequelae changes are also variable in subjects with hypoglycemia - induced brain injuries . although infarction is the most common cause of a hyper - intense lesion on diffusion magnetic resonance imaging ( mri ) , hypoglycemia also exhibits similar findings on diffusion - mri . previous literature reports that reversibility of hyper - intense lesion in diffusion - mri indicates the good prognosis . and laminar necrosis of the cerebral cortex , neuropathologically characterized by delayed selective neuronal necrosis , results from hypoglycemic encephalopathy and other brain diseases . here we report a 68-yr - old male who suffered diffuse brain injuries following an episode suggestive of prolonged hypoglycemia and showed reversible hyper - intense lesions on diffusion - mri and laminar necrosis of the cerebral cortex . a 68-yr old male with a 10-yr history of type 2 diabetes receiving a biphasic insulin analogue was brought into the emergency room by ambulance after being found in an unresponsive state by his colleague at his home . the patient lived alone , and he was in his usual state of health when he was last seen 3 days ago . on arrival , the patient 's physical exam was unremarkable except for his neurological examination . he could not open his eyes spontaneously and his pupils were equal , round , and reactive to light and accommodation , there were no corneal reflexes and doll 's eye reflexes were present . he had no purposeful speech and did not withdraw to nail bed pressure in all extremities . blood pressure was 122/80 mmhg ; pulse 75 beats / min , respiratory rate 20 breaths / min ; and temperature 36.1. the blood glucose was found to be 24 mg / dl , which lead to immediate administration of 10% glucose with a bolus followed by continuous infusion . during oxygen administration , arterial ph was 7.40 , pa02 78.6 mmhg , pac02 33.1 mmhg , base excess-3.9 mm / l , and oxygen saturation 91.4% . other chemistry results were unremarkable except for ldh ( 468 iu / l , reference rage : 240 - 460 ) and ck ( 265 iu / l , reference rage : 38 - 160 ) . computed tomography scans showed no findings of acute cerebrovascular injury except for non - prominent diffuse brain edema . this combination of test results suggested that the patient 's severe hypoglycemia was most likely caused by exogenous insulin or perhaps insulin receptor antibodies . neuroimaging with a 1.5 t mr scanner ( magnetom vision , siemens medical solutions , erlangen , germany ) on hospital day 2 showed multiple bilateral hyper - intense lesions at the cortex ( frontal , temporal , parietal and occipital lobes ) with gyral distribution , hippocampus , caudate , globus pallidus and putamen on diffusion - mri and hypo - intense lesions on apparent diffusion coefficient ( adc ) map ( fig . this was prominently seen in the occipital lobe . low signal intensity at t1-weighted image and high signal intensity at t2 weighted image lesion were seen at the same area ( fig . these abnormalities were global in appearance and did not conform to vascular distributions ; furthermore , they look like a train track . following mr angiography of we performed function neuroimaging single photon emission computed tomography ( spect ) with 99mtc - hmpao ) to look for cerebral perfusion defects on hospital day 8 . his electroencephalographic examinations on hospital day 10 showed a moderate diffuse cerebral dysfunction but no definite epileptiform discharge . during the supportive medical management in icu , there was no event and the patient 's mental and neunological changes were not noticed . follow - up mri on hospital day 22 showed a reversal of the hyperintensity lesions on diffusion - mri and the hypointensity lesions on adc map ( fig . the t1 and t2-weighted images showed linear high signal intensity selectively along the cerebral cortex in the cortical regions of bilateral hemisphere and the basal ganglia with severe parenchymal loss , characteristic of cerebral cortical laminar necrosis ( fig . the neurologic deficits and radiologic images are variable in subjects with hypoglycemia - induced brain injuries . of the mri image , diffusion - mri is a neuroimaging technique that evaluates the movement of water molecule along random pathways , detecting the tissue injury as in acute cerebral damages . although infarction is the most common cause of such a hyper - intense lesion on diffusion - mri , hypoglycemia also exhibits similar findings on diffusion - mri . despite similar findings on diffusion - mri in both infarction and hypoglycemia , their mechanisms are distinct ( 3 ) . in most reported cases with focal brain lesions associated with hypoglycaemia , the brain lesions were transient and the reversibility of both hypoglycemic coma and hyper - intense lesions on diffusion - mri was also reported ( 2 , 4 ) . however , in some cases with extensively involved brain lesion such as cerebral cortex or basal ganglia , permanent brain damage following hypoglycemia was reported ( 5 - 7 ) . in spite of reversibility of hyper - intense lesion of diffusion mri , our case also showed extensive involvement of cerebral cortex and there was no improvement of patient 's neurologic condition . the most vulnerable areas of hypoglycemia - related brain injuries are the involvement of hippocampus , basal ganglia , and cortical and subcortical areas in adults ( 2 , 4 , 5 , 7 - 11 ) . of the limited reported cases , neurologic recoveries and good prognosis were found those who were affected on the cortex sparing the basal ganglia ( 2 , 4 , 8) . the well - documented characteristics of severe brain damage following hypoglycemia are the affected areas of the parietal and occipital lobes ( 3 , 12 , 13 ) , and progressive parenchymal loss of predominant occipital lobe ( 14 ) in the newborn . our case showed multiple bilateral hyper - intense lesions at the cortex , hippocampus , caudate , globus pallidus , and putamen . this was prominently seen in the occipital lobe , and severe parenchymal loss in bilateral hemisphere and the basal ganglia was seen on a follow - up mri . the importance of duration of hypoglycemia was demonstrated in non - human primates : permanent neurological damage after profound hypoglycemia lasting 6 hr was seen in 73% of cases , with a mortality rate of 14% ( 15 ) . we have no good information on precisely how long the hypoglycemia was present in this patient , so the length of hypoglycemia remains pure speculation . aoki et al . ( 2 ) suggested that diffusion - mri is a useful tool for early diagnosis of severe hypoglycemia ( 16 ) and predicting prognosis ( 17 ) . if the hyper - intense lesions regress in the second image , the patient will likely recover . however , if the hyper - intense lesions do not regress in the second image , the outcome will be poor . they noted that they had no information on the time necessary for hyper - intense lesions on diffusion - mri to disappear in humans after glucose infusion , and signal intensity reversibility in their patient occurred within 10 days . our case showed similar findings and reversible changes of signal intensity on diffusion - mri at 22 days after admission . however , the patient showed no recovery from any neurologic deficit , and the reversibility of signal intensity on diffusion - mri did not correlate with a good prognosis . cerebral cortical laminar necrosis , neuropathologically characterized by delayed selective neuronal necrosis of the cerebral cortex , is a well - known consequence of encephalopathies such as hypoglycemic encephalopathy , cerebrovascular disease , or status epilepticus ( 18 , 19 ) . mri studies have reported that cortical laminar necrosis is visualized as high - intensity areas on t1-weighted imaging during the subacute period in hypoglycemic encephalopathy ( 4 ) , brain infarction ( 18 , 19 ) . and others , and the t2-weighted image shows low or high intensity . necrosis , with the appearance of marked cytolysis and interstitial edema , occurs within a few days . this is followed by resorption , with the subsidence of edema and the phagocytosis of necrotic material , and results in fat - laden macrophages depositions from the 7th to the 42nd day . in histologic studies , hemorrhagic foci have also occasionally been documented in patients with watershed cortical involvement ( 20 ) . in our subject , a follow up mri illustrated the cortical laminar necrosis meaning the severe parenchymal loss and linear high - signal intensity selectively along the cerebral cortex in the cortical regions of bilateral hemisphere and the basal ganglia on t1-weighted image . one might also argue that there may have been other components such as infarction or hypoxia causing the brain injuries in this patient . however , there was no objective evidence or documented episode of hypotension , acidosis , other drug intoxication , and infection before admission , or status epilepticus in this subject . and abnormal mr images were global in appearance and did not conform to vascular distributions ; furthermore they looked like a train track . in addition , mr angiography and conventional angiography of the brain and neck showed no abnormalities . though our subject showed reversible hyper - intense lesions in diffusion - mri , the subsequent mr images showed laminar necrosis of the cerebral cortex , and patient 's neurologic condition failed to improve . in conclusion , we have described a patient who suffered brain injuries following an episode suggestive of prolonged hypoglycemia . it was previously reported that reversibility of hyper - intense lesions in diffusion - mri indicates the good prognosis . the subject , however , showed reversible hyper - intense lesions but had a poor prognosis . further studies are needed to validate the clinical correlation of the lamina necrosis in subject with hypoglycemic brain injury . we tentatively suggest that cerebral cortical laminar necrosis might be another clue for predicting the poor prognosis in a subject with hypoglycemic injuries .
we report a case of 68-yr - old male who died from brain injuries following an episode of prolonged hypoglycemia . while exploring controversies surrounding magnetic resonance imaging ( mri ) findings indicating the bad prognosis in patients with hypoglycemia - induced brain injuries , we here discuss interesting diffusion - mri of hypoglycemic brain injuries and their prognostic importance focusing on laminar necrosis of the cerebral cortex .