Case Report
Localized Reversible Reduction of Apparent Diffusion
Coefficient in Transient Hypoglycemia-Induced Hemiparesis
J. Böttcher, MD; A. Kunze, MD; C. Kurrat, MD; P. Schmidt, MD; G. Hagemann, MD;
O.W. Witte, MD; W.A. Kaiser, MD, MS
Background and Purpose—The pathophysiology of hypoglycemia shares a common mechanism with cerebral ischemia,
but so far, little is known regarding MRI of humans with hypoglycemia.
Methods—We report a patient with left hemiparesis and dysarthria associated with a blood glucose level of 1.7 mmol/L.
The patient recovered completely after glucose infusion.
Results—The initial diffusion-weighted imaging (DWI) showed increased signal intensities and a reduction of apparent
diffusion coefficient (ADC) values localized in the corpus callosum (splenium) and asymmetrically in the corona
radiata. After 48 hours, follow-up revealed complete recovery of DWI and ADC signal abnormalities.
Conclusion—To our knowledge, this is the first presentation of a case with transient hypoglycemia-induced focal
neurological deficits revealing completely reversible MRI changes in terms of disturbed DWI and ADC with a peculiar
as yet undescribed topography. (Stroke. 2005;36:e20-e22.)
Key Words: apparent diffusion coefficient 䡲 diffusion-weighted imaging 䡲 hypoglycemia
䡲 magnetic resonance imaging

S

evere hypoglycemia can cause a variety of different
neurological symptoms, ranging from focal deficits to
severe coma and death.1,2 Especially in the setting of acute
onset, it can be difficult to differentiate hypoglycemia-related
symptoms from stroke.3
MRI techniques, particularly diffusion-weighted imaging
(DWI) and apparent diffusion coefficient (ADC) mapping,
are the most useful tools in diagnosing early ischemic injury.4
The detailed mechanism for the alterations of DWI and ADC
values in the event of acute ischemic brain injury is not
precisely understood. However, ischemia results in metabolic
energy failure with a disruption of water and electrolyte
homeostasis consecutively leading to impairment of cell
membrane potential. The ionic imbalance provokes an osmotically driven flow of water into the cells and a consecutive
reduction of the extracellular space (ECS). It has been
speculated that the reduction of the ECS and the diminished
diffusibility of water intracellularly contribute to the changes
of ADC in ischemia. Complete or partial recovery of ADC
reductions could be demonstrated in transient ischemia,
suggesting that early ADC decreases do not necessarily
represent irreversible tissue damage.4,5 ADC reductions are
not unique to ischemia and occur in different pathological
conditions, such as seizures, spreading depression, excitotoxic cerebral injuries, as well as hypoglycemia.4,5 However,
the pathophysiology of these conditions and therefore most
likely the reasons for ADC changes are heterogenous.

In animal in vivo studies, the visualization of
hypoglycemia-induced changes of signal intensities for DWI
and ADC imaging is documented in detail and could be
reversed by glucose intake.5 We report a case with transient
hypoglycemia-related neurological deficits combined with
reversible DWI and ADC changes in the corona radiata
asymmetrically and in the splenium of the corpus callosum.

Materials and Methods
Case Report
A 77-year-old male patient with a 15-year history of type 2 diabetes
who was receiving a total of 4 mg Glimepiride daily developed a
progressive reduction of mental status and dysarthria 1 day prior to
admission. He had no history of vascular disease but a renal
insufficiency with serum creatinine of 488 ␮mol/L (5.51 mg/dL) and
proteinuria (4964 mg/L). Initial neurological examination revealed a
somnolent patient with left hemiparesis (Medical Research Council
grade 3), including facial paresis and dysarthria.
MRI examination was performed immediately, and the following
laboratory findings could be documented: plasma glucose level of
1.71 mmol/L, serum chloride of 116 mmol/L, serum potassium of
7.09 mmol/L, and serum calcium of 2.03 mmol/L. The patient
showed a marked recovery within 2 hours after glucose substitution
and was back to normal 12 hours later.

Neuroimaging
MRI was performed on a 1.5T magnetic resonance (MR) scanner
(Sonata; Siemens) with standard sequences (diffusion-weighted sequence, fluid-attenuated inversion recovery [FLAIR] sequence, MR

Received October 15, 2004; final revision received November 21, 2004; accepted November 25, 2004.
From the Department of Diagnostic and Interventional Radiology (J.B., C.K., P.S., W.A.K.), and Department of Neurology (A.K., G.H., O.W.W.),
Friedrich-Schiller-University Jena, Germany.
Correspondence to Dr Joachim Böttcher, Department of Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, Erlanger Allee
101, 07747 Jena, Germany. E-mail joachim.boettcher@med.uni-jena.de
© 2005 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org

DOI: 10.1161/01.STR.0000155733.65215.c2

e20
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Böttcher et al

Figure 1. A, Initial DWI (repetition time/echo time/␣ 4100/96/90;
␤⫽1000 s/mm2; field of view 230 mm; matrix: 128⫻128) with
increased signal intensities in bilateral corona radiata and splenium. B, Initial ADC maps with signal reduction also in bilateral
corona radiata and splenium corresponding to DWI images.

perfusion and MR angiography of intracerebral and extracerebral
arteries, T1-weighted spin-echo, and T2*-weighted sequence). ADC
maps were automatically calculated from DWI.

Results
The initial MRI showed circumscribed areas of reduced
diffusion in the corona radiata asymmetrically and in the
splenium of the corpus callosum. The DWI changes with a
maximal relative 62.9% increase compared with unaffected
cerebral tissue were localized in the splenium, the corona
radiata of the right hemisphere, and, to a lesser extent, in the
left corona radiata, but were generally not as pronounced as
with acute ischemia. The reduction of ADC (maximal relative
signal decline 61.3%) clearly showed a hypointense signal
change (Figure 1) and revealed absolute values
(unit⫻10⫺4 mm2/s) of 3.07 in the splenium of the corpus
callosum, 4.75 in the left, and 4.10 in the right corona radiata.
All values returned to normal until follow-up.
T1-weighted images revealed no intracerebral hemorrhage,
whereas FLAIR sequence and T2*-weighted images showed
no significantly increased signal in the locations of reduced
diffusion (Figure 2).
MR angiography documented no hemodynamically relevant stenoses or vasospasm of the extracerebral and intracerebral arteries. MR perfusion revealed no perfusion deficit.
Follow-up after 48 hours showed completely normalized MR
images.

Discussion
To our knowledge, this is the first case of a patient with
transient hypoglycemia-induced hemiparesis and reversible
ADC reduction and signal increase in DWI experiencing a
complete recovery of all neurological symptoms and pathological MR alterations after glucose intake.
In many reports, different theories to explain the neurological deficits after hypoglycemia were discussed.1,5–7 In our
case, significant cerebral vasospasm and asymmetric cerebral

MRI in Hypoclycemia-Induced Hemiparesis

e21

Figure 2. A, Initial FLAIR sequence (repetition time/echo time/
TI/␣ 9000/108/2500/150; field of view 184 mm; matrix:
448⫻512). B, T2*-weighted sequence showed images without
visible increase of signal intensities as opposed to DWI and
ADC maps (considering a different slice angulation between the
imaging sessions because of patient’s movement).

blood circulation could be excluded mostly by normal MR
angiography and perfusion imaging.
MRI, in particular, and, in a very sensitive manner, DWI
and ADC, could identify changes in brain water diffusion
during hypoglycemia regarding in vivo animal models.4,5 In
this respect, hypoglycemia shows similar MR findings as
acute ischemia, but the underlying pathophysiology is distinct. Nevertheless, it is assumed widely that severe hypoglycemia causes cerebral energy failure and leads to a reduction
of cell membrane ionic pump activity and a consecutive shift
of cerebral water from ECS to intracellular space. Hasegawa
et al5 suggest that this is a substantial mechanism contributing
to the ADC changes in hypoglycemia. Although the exact
mechanism underlying the ADC reductions is not known in
detail, the results of this and several experimental studies
support the assumption that ADC decline is a marker of
unspecific ECS shrinkage.
The fast recovery of the clinical symptoms and the imaging
abnormalities can be explained by the intravenous glucose
supplementation, which was initiated immediately after the
first MRI and allows exclusion of ischemic origin. Similarly,
a fast normalization of signal abnormality has been reported
in animal models of hypoglycemia.5 Most reports of MRI
changes in hypoglycemic patients so far were reported on
more severely affected patients who were in a vegetative
state.2,7
Secondly, the anatomical locations of areas with
hypoglycemia-induced alteration of diffusion have not been
described previously in humans. In earlier reports, MR signal
changes were localized in the basal ganglia, the pons, the
temporal and occipital cortex, and the hippocampus.1,2,6,7
In an in vivo animal study of hypoglycemia, more detailed
analysis is available that demonstrated severe and widespread
ADC abnormalities only after the onset of isoelectricity of rat
brains.5 However, earlier ADC decline, which was asymmet-

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Stroke

March 2005

rical, was observed in isolated cortical and periventricular
areas, mainly the caudoputamen, and furthermore, 10 minutes
after glucose infusion, ADC normalization was complete
except in the periventricular regions.5 The asymmetry of the
transient periventricular ADC changes, as well as the reversibility of the hemiparesis after glucose infusion in our patient,
corresponds well with these findings and suggests that the
hypoglycemia has not been long lasting and probably was not
as severe as to cause permanent cell injury.
Hasegawa et al5 speculate that the localized ADC changes
might be caused by regional imbalances between energy supply
and demand, spreading depression, or an excitotoxic mechanism. There are no data on the corpus callosum in this study.
Profound MR signal changes (in T2*-weighted imaging
and DWI) in the splenium of the corpus callosum have been
reported in a variety of different pathological conditions
(infectious diseases, treatment with or withdrawal from antiepileptic drugs), partially based on histopathological studies,
without unraveling the reason for this localized vulnerability.

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Localized Reversible Reduction of Apparent Diffusion Coefficient in Transient
Hypoglycemia-Induced Hemiparesis
J. Böttcher, A. Kunze, C. Kurrat, P. Schmidt, G. Hagemann, O.W. Witte and W.A. Kaiser
Stroke. 2005;36:E20-E22; originally published online February 3, 2005;
doi: 10.1161/01.STR.0000155733.65215.c2
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2005 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628

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