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Neuroradiology (1984) 26:517-521

© Springer-Verlag1984

Reno-cerebral oxalosis induced by xylitol
B. Ludwig 1, E. Schindler1, J. Bohl 2, J. Pfeiffer3 and G. Kremer4
Departments of 1Neuroradiology,2Neuropathology,3Pathology,and 4Internal Medicine, University Hospital Mainz, FRG

Summary. A 20-year-old man suffering from Crohn's
disease developed coma and generalized seizures
following ileocecal resection. During postoperative
parenteral feeding he received xylitol in an unusually
high concentration. CT examinations a few days before death showed intense hypodensity and swelling
of brainstem and basal ganglia and increasing triventricular dilatation. Autopsy revealed, mainly in the
brainstem and cerebellum, a destruction of intracerebral, intracerebellar and leptomeningeal vessel walls
by birefringent crystals (probably calcium oxalate),
an early inflammatory reaction and severe brain edema with final tonsillar herniation. The same crystalloid deposits were found in the kidneys.

Key words: Xylitol-infusions - calcium oxalate crystals in reno-cerebral vessel walls - perivascular inflammatory reactions and brain edema - computed
tomography

In 1972 similar autopsy findings had first been
reported in Germany [4]. In all these cases, intravenous infusions containing high doses of xylitol had
been administered to the patients.
These alarming results led to the recommendation to limit the quotidian dose of xylitol to a maximum of 1.5 g/kg body weight [1].
Meanwhile some further reports on the toxic effects of xylitol have been published, especially in
Germany, where xylitol is still used [7, 17, 19], the effects occurring when xylitol is administered in high
doses or frequently within a short time. Clinically,
the patients show neurological or psychopathological signs of various degrees.
We report the case of a 20-year-old male patient
with striking cerebral changes on CT, whose autopsy
revealed a reno-cerebral oxalosis induced by xylitol
[131.

Case report
Intravenously infused xylitol may be used for supplying the organism with carbohydrates when the
metabolism of glucose is disordered e. g. after trauma
or surgery [21].
In 1970 Australian authors reported severe complications following the administration of high doses
of xylitol even with fatal outcome in some cases [24].
At autopsy, marked calcium oxalate precipitations
were found in the renal tubules. Such deposits could
also be seen in the walls of small intracerebral vessels.
Because of these findings, xylitol has been withdrawn in Australia and in the United States.
At the same time, an inquiry performed by the
Pharmaceutic Committee of the German Medical
Association did not reveal any siriaiiar observations.

The patient suffered from Crohn's disease with stenosis of the terminal ileum. Repeatedly treated with
azulfidine and corticosteroids, the patient's condition was satisfactory for some years. Later, unilateral
hydronephrosis caused by an inflammatory conglomerate compressing the ureter led to deterioration. An ileocecal resection was therefore performed.
During 9 postoperative days of parenteral nutrition the patient whose body weight was 50 kg was
treated with a quotidian dose of 150 g xylitol, that is
double the maximal amount recommended by the
Pharmaceutic Committee. The postoperative course
was uneventful, but after one week septic fever occurred. Twelve hours later, after several seizures, the
patient lost consciousness. A severe metabolic acidosis, disorder of the electrolyte balance and acute renal failure developed.

518

Fig. 1. Postcontrast CT on the 7th postoperative day: hypodensity and swelling of brainstem and deep grey nuclei without pathological
enhancement, bilateral edema of the internal and external capsules, partial compression of the supratentorial ventricles and subarachnoid
spaces

CT was performed on the 7th postoperative day
(Fig.l): There was hypodensity and swelling of the
brainstem, the basal ganglia and the thalami with
edema of the internal and external capsules on both
sides. The 3rd ventricle and the frontal horns of the
lateral ventricles were narrow, the temporal and occipital horns slightly enlarged, the sulci ill-defined.
The quadrigeminal cistern was narrow, the 4th ventricle normal. Pathological enhancement was not
seen.

Plain CT performed on the following day (Fig. 2)
showed that the cisterns surrounding the brainstem
were almost obliterated. The lateral ventricles were
dilated, especially the occipital horns, and their outlines were ill-defined. The supratentorial hypodense
area had increased in size, reaching the cortex.
At this time the patient's condition further deteriorated. He became anuric on the next day and his
respiration ceased. Two days later EEG was isoelec-

tric and death occurred on the l l t h postoperative
day.
Autopsy revealed marked signs of elevated intracranial pressure with tonsillar herniation. Microscopically severe lesions of intracerebral, intracerebellar and leptomeningeal vessels with deposits of
birefringent crystals were found. These crystals were
morphologically identical with calcium oxalate crystals (Fig.3). The pathologic changes of the vessel
walls, with perivascular inflammatory reactions and
brain edema were particularly pronounced in the
brainstem and cerebellum. Crystalloid concretions
were also found in the renal tubules (Fig. 4).

Discussion

The localization of these pathological changes and
their exclusive distribution in the kidneys and the

519

Fig.2. Precontrast CT on the 8th postoperative day (3 days before death): progression of the hypodense and space-occupying changes,
dilation of the lateral ventricles

brain characteristically demonstrate the type of
oxalosis, which can be induced by xylitol [8, 25].
In primary oxalosis, however, caused by congenital enzyme defects, only scanty cerebral oxalate deposits inconstantly occur, despite massive oxalate
precipitations in all other organs [11, 15].
The same can be assumed for most of the secondary oxaloses [2] which are defined by disturbances of
the oxalic acid metabolism. The latter develops either endogenously e.g. in renal insufficiency [26] or
exogenously, dependent on intoxications, for instance caused by oxalic acid [27], ethylene glycol [18,
23] or the anaesthetic methoxyfluran [9]. Hyperoxalemia occurring as well in primary as in secondary oxaloses does not lead to severe cerebral changes because the blood brain barrier remains undamaged

[20].
In xylitol-induced oxalosis, however, the insoluble and therefore inert calcium-oxalate in the cere-

bral vessel walls is probably just the final product of
a series of reactions, which can not yet be biochemically entirely clarified [10, 12].
Intoxication caused by the anti-freeze ethylene
glycol induces the same renal and cerebral damage
as xylitol [4, 18, 19]. In a lethal case of ethylene glycol
intoxication we were also able to find at autopsy the
same birefringent deposits of calcium oxalate in
cerebral, cerebellar and leptomeningeal vessels as
well as in renal tubules. Therefore a common biochemical pathway can be supposed [16, 20, 22].
Indeed, Maier recently reported a case of sublethal intoxication with ethylene glycol showing a reversible density decrease of the brainstem, the basal
ganglia and the thalami in CT [14].
In an overdosage of xylitol as well as in intoxication with ethylene glycol, the precursors of oxalic acid, developing in the liver, especially glycolic acid,
are probably the real toxic substances. The inflam-

Fig.3a and,b, a Intracerebral blood vessels with acute inflammatory reactions in the vessel wall (scale bar 50 ~t) b Localized deposits of a
birefringent crystalline material (probably calcium oxalate) in a blood vessel wall at a higher magnification and with closed polarizing filters (scale bar 10 p,). Paraffin embedding, HE staining

Fig. 4. Renal cortex with circumscribed deposits of a birefringent crystalline material (probably calcium oxalate) inside the renal tubules.
The polarizing filters are more open on the left and more closed on the right side (scale bar 50 Is). Paraffin embedding, HE staining

521

matory cerebral changes and the metabolic acidosis,
occurring in both intoxications, had been attributed
to these substances too [5, 6].
It is questionable whether there is any connection
with Crohn's disease or the ileocecal resection in this
patient, even when, because of a disturbance of the
oxalic acid resorption, an enterogenous hyperoxaluria or hyperoxalemia may develop under these circumstances [12]. In some reported cases of cerebral
oxalosis appearing after ileocecal resection [3] the
cerebral changes might have been caused by infusions of xylitol too [20].

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Received: 12 December 1983

Dr. B. Ludwig
Abteilung ffir Neuroradiologie
Universit~itskliniken Mainz
Langenbeckstral~e 1
D-6500 Mainz
Federal Republic of Germany