Reversibile Quadriplegia and Nonketotic Hyperosmolar Coma

Is it an exceptional association or an overlooked complication?

A thrombotic stroke or cerebro-pontine myelinolysis associated with high serum osmolarity and cerebral edema are well-known complications of hyperosmolar nonketotic coma (1). Although critical illness polyneuropathy (CIP) is not included in the “textbook” differential diagnosis, there is one case report showing an association of CIP to hyperosmolar nonketotic coma (2).

We report on a case of a 56-year-old white woman with unknown diabetes who was admitted to the emergency department because of fever, chills, arthromyalgia, and fatigue. At presentation, she was confused, lethargic, and dehydrated. Initial laboratory studies revealed blood glucose 916 mg/dl, creatinine 1.7 mg/dl, sodium 146 mEq/l, and potassium 5.3 mEq/l. Plasma osmolarity was 342 mOsm/l. Urinalysis was negative for ketones.

The patient was diagnosed with hyperosmolar nonketotic coma and treated with normal saline, potassium, continuous insulin infusion, and antimicrobial therapy according to culture results. Strict blood glucose control was achieved in a few days and maintained thereafter with four daily insulin injections. Anti-GAD and –islet cell antibodies were negative, while fasting serum C-peptide was 6 ng/ml.

During days 1–4, the patient remained in the intensive care unit. The neurological examination revealed pupils that were round, equal, and light responsive. The tendon reflexes were present and normal, and there were no symptoms or signs of peripheral neuropathy. On day 5, neurological examination revealed all four limbs to be flaccid and areflexic. A brain computed tomography scan was normal, and lumbar puncture with analysis of cerebrospinal fluid showed normal concentration of protein and no nucleated cells. Since electromyogram was consistent with severe axonal sensorimotor peripheral neuropathy, other conditions such as Guillain-Barré syndrome were excluded and a diagnosis of CIP was made.

On day 30, the patient’s limbs were responsive to pain and she was able to voluntarily move her arms, while the lower limbs remained paretic. A further electrophysiological study showed improvement in the axonal damage; in particular, a marked increase in upper limb sensory nerve action potential amplitudes was observed, whereas compound motor action potentials remained compromised. On day 60, the recovery in motility was complete in her arms but only partial in her legs. Four months after the admission, the patient was able to walk with support.

Severe and acute hyperglycemia should be included in the list of other well-known conditions such as coma, severe lung disease, sepsis, multiple trauma, postsurgical complications, and shock, which may be complicated by CIP, by different mechanisms (3,4). Consistent with this view, in vivo and in vitro animal studies have shown that acute and severe hyperglycemia (>500 mg/dl) can result in increased apoptosis of neurons and reduced neurite growth (5).

At variance with classical diabetic neuropathy, which is mainly related to poor blood glucose control and diabetes duration, in our patient, CIP was mainly caused by coma, sepsis, and, as we suggest, severe hyperglycemia. The apparent delayed onset is consistent with CIP; despite CIP affecting 80% of intensive care unit patients after 7 days, the occurence of CIP on day 5 is not surprising (2). In fact, the woman was probably exposed to a high concentration of glucose (>500 mg/dl) for a few days before admission. So, in this patient, the role of hyperglycemia in causing CIP is both direct (by means of its acute neurotoxicity) and indirect (by causing the sepsis).

In such an acute clinical picture, CIP could not be an exceptional event, but rather a relatively common complication that should be kept in mind. For all these reasons, we recommend that electromyogram be performed in patients with hyperosmolar nonketotic coma and sudden-onset quadriplegia. The aim is not only to differentiate CIP, which is reversibile in 80% of cases (4), from more usual complications (mainly Guillain-Barré syndrome) with worse prognosis, but also to find out the prevalence of this condition in diabetic patients.