Diabetes Research and Clinical Practice 68 (2005) 75–80

www.elsevier.com/locate/diabres

Case report

Central pontine and extrapontine myelinolysis associated

with type 2 diabetic patient with hypokalemia
Mitsuyo Shintania,*, Mariko Yamashitab, Atsuo Nakanoa, Daisuke Aotania,
Koji Maedaa, Toru Yamamotob, Haruo Nishimuraa
a
Department of Endocrinology and Diabetes, Osaka Saiseikai Nakatsu Hospital, 2-10-39 Shibata, Kita-ku, Osaka 530-0012, Japan
b
Department of Neurology, Osaka Saiseikai Nakatsu Hospital, 2-10-39 Shibata, Kita-ku, Osaka 530-0012, Japan
Received 9 March 2004; received in revised form 1 July 2004; accepted 11 August 2004
Available online 12 October 2004

Abstract

Central pontine myelinolysis (CPM) is a demyelinating disease of the pons often associated with the demyelination of
extrapontine areas of the central nervous system. Although the etiology and pathogenesis are unclear, CPM is usually associated
with hyponatremia or its rapid correction, and chronic alcoholism is also a common underlying condition. We observed a 43-
year-old man with diabetes mellitus who developed central pontine and extrapontine myelinolysis with no apparent evidence of
hyponatremia, serum hyperosmolality or associated rapid correction, or history of alcohol abuse. On admission, the patient was
lethargic with dysarthria, dysphagia, and mild tetraparesis and his face and lower extremities were severely edematous.
Laboratory examination showed normoglycemia and normonatremia, although hypokalemia, elevated HbA1c, and nephrotic
syndrome were also present. Magnetic resonance imaging (MRI) revealed abnormal signal intensity in the pons, the deep layers
of the cerebral cortex, and the adjacent white matter consistent with central pontine and extrapontine myelinolysis. Generalized
edema was reduced by the use of diuretics and extracorporeal ultrafiltration without significant changes of serum sodium or
osmolality. His consciousness level and paresis gradually improved within a few weeks. Our patient is a rare case of CPM
associated with diabetes without apparent evidence of sodium or glucose imbalances.
# 2004 Elsevier Ireland Ltd. All rights reserved.

Keywords: Central pontine myelinolysis; Extrapontine myelinolysis; Hypokalemia; Nephrotic syndrome

1. Introduction with the rapid correction of hyponatremia [1,2].

Central pontine and extrapontine myelinolysis are
neurologic complications that have been associated
* Corresponding author. Tel.: +81 6 6372 0333;
fax: +81 6 6372 0339.
E-mail address: mitsuyo@kuhp.kyoto-u.ac.jp (M. Shintani).
Pontine and extrapontine myelinolysis have also been
described in association with other underlying
conditions, such as alcoholism and malnutrition
[3,4]. These conditions are characterized by loss of
myelin with the sparing of neuron in the central pons
as well as certain extrapontine sites, such as the
internal capsule, basal ganglia, cerebellum, and

0168-8227/$ – see front matter # 2004 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.diabres.2004.08.005
76 M. Shintani et al. / Diabetes Research and Clinical Practice 68 (2005) 75–80

cerebrum. Chronically, CPM is characterized by rapid Table 1

Laboratory data on the present admission
evolving paraparesis or quadriparesis with pseudo-
bulbar symptoms, such as dysarthria and dysphagia. CBC
WBC 7300 ml
1
We describe a case of diabetic patient accompanied
RBC 429  104 ml
1
by central pontine and extrapontine myelinolysis Hb 11.5 g/dl
without hyponatremia, hyperosmolality or associated Ht 35.7%
rapid corrections. Plt 52.9  104 m
1
Serological
CRP 2.49 mg/dl
2. Case report Urinalysis
Protein 300"
A 43-year-old man with a history of type 2 Glucose

diabetes for more than 10 years was admitted to our Ketone body +
Occult blood 2+
hospital on April 9, 2003, due to lethargy, dysarthria,
pH 7.0
dysphasia, mild tetraparesis, and severe generalized WBC 3+
edema.
Arterial blood gas analysis
He was previously admitted to our hospital due to pH 7.460
nephrotic syndrome in June 2002, at which time, pO2 73.5 mmHg
diabetic nephropathy was diagnosed. Vibration sense pCO2 39.0 mmHg
was decreased and neurogenic bladder dysfunction HCO3 27.1 mEq/l pl
was also diagnosed. Proliferative diabetic retinopathy BE 3.2
was observed and photocoagulation was recom- Blood chemistry
mended. His condition was complicated with diabetic Na 146 mEq/l
K 2.6 mEq/l
microangiopathy, but he did not have cerebrovascular
Cl 108 mEq/l
disease or ischemic heart disease. After his discharge, Ca 7.6 mg/dl
he discontinued his doctor visit and eventually lost his P 4.4 mg/dl
sight due to diabetic retinopathy. BUN 18.6 mg/dl
Laboratory data on the present admission (Table 1) Cr 1.8 mg/dl
UA 6.7 mg/dl
showed hypokalemia (2.6 mEq/l, normal range: 3.5–
TP 4.7 g/dl
4.8), hypoalbuminemia (1.8 mg/dl, normal range: 3.8– Alb 1.8 g/dl
5.3), proteinuria, and hyperlipidemia, but serum Ch-E 291 IU/l
sodium (sodium; 146 mEq/l, normal range: 135– GOT 12 IU/l
147), osmolality (297 mOsm/kg, normal range: 275– GPT 4 IU/l
LDH 175 IU/l
295) and glucose (101 mg/dl, normal range: 60–
g-GTP 9 U/l
109 mg/dl) were almost normal. HbA1c was, however, T-cho 351 mg/dl
at a high value of 9.1%. Magnetic resonance imaging TG 192 mg/dl
(MRI) of the brain (Fig. 1(a)–(d)) revealed increased HDL 53 mg/dl
signal intensity in the central portion of pons, the deep LDL 282 mg/dl
Glucose 101 mg/dl
layers of the cerebral cortex and the adjacent white
HbA1c 9.1%
matter consistent with central pontine and extrapon-
tine myelinolysis in T2 weighted images. The T1
weighted images decreased in intensity. CSF exam-
ination did not reveal any remarkable changes. These without significant changes of serum sodium or
clinical images seemed to be consistent with central osmolality (Fig. 2). His consciousness and paresis
pontine and extrapontine myelinolysis. gradually improved relative to the improvement of
The patient’s generalized edema was reduced after serum potassium level and nutrition. T2 weighed MRI
2 weeks by the use of the diuretic furosemide and by images after 6 months showed slight reduction of the
the extracorporeal ultrafiltration method (ECUM) high intensity in the pons (Fig. 1(e)).
 M. Shintani et al. / Diabetes Research and Clinical Practice 68 (2005) 75–80 77

Fig. 1. (a) Sagittal T2-weighted image shows increased intensity in the pons. (b) Coronal T2-weighted image shows increased intensity in
subcortical white matter and pons. (c) Axial T1-weighted image shows decreased intensity in pons. (d) Axial T2-weighed shows increased
intensity in the pons. (e) Axial T2-weighted image, performed after 6 month, shows reduction of the hyperintense signal in pons.

3. Discussion ized edema after the admission, at which time neither

Central pontine and extrapontine myelinolysis are
demyelinating disorders, which were originally
described by Adams et al. [3]. Although the
pathogenesis has not been elucidated, most CPM
cases have been reported in association with rapid
correction or overcorrection of hyponatremia [1,2].
Recently, CPM has also been reported to be associated
with an increase in serum osmolality secondary to the
development of hypernatremia [5,6]. CPM has also
been reported in cases of hyperosmolality secondary
to severe hyperglycemia and azotaemiam without
significant shifts of serum sodium [6–8]. With our
case, neither sodium nor osmolality had significantly
changed when CPM and EPM had developed. We
administered a diuretic and performed extracorporeal
ultrafiltration method to improve his severe general-
sodium nor osmolality was significantly changed. His
neurological symptoms and generalized edema
improved gradually after admission. Before admis-
sion, he had no medication including diuretics. His
serum sodium and glucose levels and osmolality were
within the normal range at the time of admission.
Magnetic resonance imaging (MRI) of the brain
(Fig. 1) revealed increased signal intensity in the
central portion of pons, the deep layers of the cerebral
cortex, and the adjacent white matter. Neither
magnetic resonance angiography (MRA) of the brain
nor ultrasonographic examination of the carotid
arteries showed atherosclerotic changes. Because
the patient did not have arrhythmia or valvular heart
diseases and his symptoms gradually improved, the
possibility of cerebrovascular disease or brain tumor
was excluded. His clinical and radiographical findings
78 M. Shintani et al. / Diabetes Research and Clinical Practice 68 (2005) 75–80

Fig. 2. Clinical course after admission. Neither serum sodium nor osmolality changed significantly during the course, although serum potassium
level was gradually improved. ECUM, extracorporeal ultrafiltration method.

were consistent with central pontine and extrapontine
myelinolysis on T2 weighted images, although the
possibility of multiple sclerosis may not be ruled out
completely.
The laboratory data showed hypokalemia at the
first examination. Because he did not use insulin,
insulin-induced shift of potassium into the cells was
not considered to be the cause of his hypokalemia. He
did not take any medicines including diuretics, licoris
or corticoids, and did not have gastrointestinal
disorders. He had no family history of hypertension
or renal dysfunction. His adrenal function was
not impaired nor was his aldosterone level high.
Arterial blood gas analysis showed a slight metabolic
alkalosis. The hypokalemia improved gradually over
the course of time. Although his serum cholesterol and
triglyceride levels were not low, total protein, albumin
and ration of albumin to globulin (A/G) were low. The
serum total protein, albumin levels and ratio of
albumin to globulin at this admission (total protein,
albumin, A/G: 4.7 mg/dl, 1.8 mg/dl, 0.6 respectively)
were much lower than those at the former admission
(5.4 mg/dl, 2.6 mg/dl, 0.9 respectively). The elevation
of ketone body level in his urine, furthermore,
suggested the presence of prolonged starvation.
His blood glucose was 101 mg/dl at the admission
although his HbA1c was high. It is thus possible that
he did not have enough potassium and food intake for
a while before his admission. Although the reason he
developed hypokalemia was not clear, metabolic
alkalosis and low potassium intake might affect the
condition. His hypokalemia was gradually improved
after admission in spite of the use of diuretics. The
improvement of hypokalemia might be, at least, due to
the increase in food intake and intravenous potassium
infusion after the admission.
It has been reported that hypokalemia may increase
the incidence of CPM during rapid correction of
hyponatremia [9,10]. The sodium- and potassium-
activated adenosine triphosphate (Na-K-ATPase),
located in the cell membrane, which transports
potassium into cells in exchange for sodium, is
critically important in the regulation of cell volume.
Potassium deficiency may be associated with a
decreased concentration of Na-K-ATPase in endothe-
lial or glial cell membranes, as reported in skeletal
muscle in vivo [11,12]. A decrease in Na-K-ATPase
activity during hypokalemia may limit the ability of
the cell to preserve its volume in the face of increasing
osmolality because of a decrease in uptake of
inorganic and organic osmolytes [9]. It is possible
that CPM developed without a significant change in
 M. Shintani et al. / Diabetes Research and Clinical Practice 68 (2005) 75–80 79

Table 2
Reported cases of central pontine myelinolysis without hyponatremia with hypokalemia
Reference Age Sex Na K Alcoholism EPMa Underlying disease
Adams et al. [3] 38 M ND 3.1 + +
Berry and Olszewski [22] 51 M ND Decreased + +
Chason et al. [14] 32 F 135 1.3 +

Cadman and Rorke [15] 3 F ND 2.8

Hematologic disease
Cadman and Rorke [15] 4 F ND 1.5

Hematologic disease
Minauf and Jellinger [16] 11 M ND 2.4


Endo et al. [17] 63 M Normal Decreased


Bahr et al [18] 59 M 137 <3 + +
Bahr et al [18] 32 F 133 2.6 +

Mukai et al. [19] 39 M Normal 1.8 + +
Nagashima et al. [23] 42 F 140 2.9

Sjögren’s syndrome, renal tubular acidosis
Sugimoto et al. [21] 31 M 140 2.8

Anorexia nervosa
This case (2004) 43 M 146 2.6
+ Diabetes
ND: not described.
a
Extrapontime myelinolysis.

serum sodium or osmolality in the presence of
hypokalemia. Although serum sodium level was not
obviously changed, serum potassium level was low in
this case. Na-K-ATPase activity in this case might
decrease though we did not determine.
His blood glucose was 101 mg/dl though the
HbA1c was high. The discrepancy between the blood
glucose level and HbA1c may not be caused by
hemoglobin abnormalities, for his HbA1c level
decreased after admission in accordance with low-
ering blood glucose levels. The discrepancy indicates
recent decrease in his blood glucose levels. The acute
or subacute change in blood glucose level might affect
the development of central pontine and extrapontine
myelinolysis.
He had nephrotic syndrome and hypothyroidism
since the former admission. Both nephrotic syndrome
and hypothyroidism can attribute to hyponatremia. It
is possible that his sodium and osmolality levels were
changed before the present admission, although those
levels were within normal range at the admission.
Few cases of CPM have been reported to have
hypokalemia without hyponatremia and Table 2 lists
these previously reported cases [3,13–21]. In these
cases, underlying diseases are alcoholism, hematolo-
gical disease, liver disease, renal tubular acidosis,
or anorexia nervosa. In our case, the underlying
conditions were diabetes with severe microvascular
complications, hypothyroidism and malnutrition due
to nephrotic syndrome and poor food intake.
This is a rare case of a diabetic patient with CPM,
who had hypokalemia without significant changes in
serum sodium or osmolality. Clinicians should be
aware of the possibility of CPM when treating diabetic
patients with neurologic disorders, even if serum
sodium or osmolality has not changed. MRI is one of
the useful tools in documenting this disease.
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