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Introduction

Wernicke’s encephalopathy is a medical emergency. Immediate treatment with thiamine is required to prevent permanent neurologic injury. Although the classical context for Wernicke’s encephalopathy is the malnourished alcoholic patient, it is seen in many other conditions in which thiamine deficiency arises. Indeed, 1 of the 3 initial cases reported by Wernicke et al in 1881 developed as a consequence of esophageal injury after the ingestion of sulfuric acid. Wernicke’s encephalopathy has been recognized with increasing frequency after bariatric surgery and with cancer . Wernicke’s encephalopathy occurring in the latter settings often results in diagnostic confusion resulting in a delay of therapy. We report 2 cases of Wernicke’s encephalopathy occurring during the course of therapy for head and neck cancer.

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Discussion

Thiamine is an essential coenzyme in intermediate carbohydrate metabolism, playing a vital role in the Krebs and pentose phosphate cycles . Thiamine deficiency alters mitochondrial function by impairing oxidative metabolism and causes selective neuronal death by diminishing thiamine-dependent enzymes, and thus, impairing glucose metabolism, cerebral metabolism of glutamate, and the generation of proteins, DNA, neurotransmitters, and radical scavengers . Because of their high dependence on oxidative metabolism and high thiamine content and turnover, certain regions of the nervous system, such as, the midline mesencephalon and cerebellar vermis, are especially sensitive to thiamine deficiency . The peripheral nerves are also very sensitive to thiamine deficiency . Damage to these vulnerable structures is responsible for the clinical presentation of Wernicke’s encephalopathy that includes mental confusion, ataxia, oculomotor abnormalities including nystagmus and ophthalmoplegia, and peripheral neuropathy.

Wernicke’s encephalopathy is frequently misdiagnosed. Less than 20% of patients display the classic triad of altered mental status, ophthalmoplegia, ataxia, and nonspecific manifestations that may herald the disorder . A sensorimotor peripheral neuropathy may dominate the clinical picture of thiamine deficiency . The appearance of the disorder in the nonalcoholic patient may be clinically confusing. Lastly, a thorough neurologic examination may be rendered difficult or impossible because of a poor level of cooperation.

Neuropsychiatric complications, particularly delirium, are common in advanced cancer. Delirium has been observed in 28% to 34% of terminally ill cancer patients at presentation and 68% to 85% preterminally . Approximately 80% of patients with Wernicke’s encephalopathy present with mental status changes, and therefore, thiamine deficiency should be considered in all patients with cancer displaying otherwise unexplained confusion or delirium . Nutritional deficiency as a cause of mental status change as well as other neurologic manifestations in the patient with cancer can be easily missed. Patients with head and neck cancer are at an especially high risk for malnutrition for several reasons. At baseline, these patients are frequently malnourished and cachectic. Therapy, specifically chemoradiation, with or without surgery, adds to the dysphagia. Heavy dependence of narcotic control of analgesia results in impaired bowel motility. Chemotherapy may result in an increased likelihood of emesis. Tube gastrostomy feedings are not universally tolerated, and delayed gastric emptying may result in bloating, reflux, and in some cases, persistent emesis. This constellation of issues results in decreased dietary intake, malabsorption, and increased metabolic consumption with elevated thiamine requirements. This phenomenon also occurs in the setting of increased carbohydrate loading in an individual with low stores, as is seen in poststarvation feeding .

In the setting of prescribed nutritional supplementation, the nutritionally depleted state may not be readily recognized, and the concern for delirium from other sources, particularly, metastatic disease, may cloud the diagnosis. Mental status changes may also be inappropriately attributed to narcotic analgesia in patients with cancer.

Once the diagnosis of thiamine deficiency is considered, treatment should begin immediately with 50 to 100 mg thiamine intravenously, with maintenance therapy for several days . As delay in treatment may increase the risk of permanent neurologic injury, specifically, an abnormality of antegrade memory (Korsakoff’s psychosis), therapy should be administered presumptively. The diagnosis can be confirmed by measuring exogenous thiamine pyrophosphate after treatment initiation if warranted. Response to treatment is generally very rapid, with restoration of sleep-wake cycles within the first day of treatment. Ophthalmoplegia typically recovers quickly, with subsequent improvements in ataxia. Cognitive function recovers more slowly. Careful examination, even after long-term thiamine therapy, frequently demonstrates persistent clinical findings of nystagmus, ataxia, persistently disturbed mental function, and peripheral neuropathy .

In general, the nutritional requirements in overall energy intake in the head and neck cancer population are well appreciated. The impact of chemoradiatiotherapy during head and neck cancer therapy on swallowing and dysphagia is similarly acknowledged. Although this is generally measured and monitored in weight loss, the emphasis on energy intake frequently masks an essential awareness of nutritional wellness. We present 2 cases of Wernicke’s encephalopathy occurring when dietary maintenance was impaired by complications of therapy, specifically intractable emesis. As trends in therapy for head and neck cancer have shifted from radiation alone to the almost universal use of adjuvant chemotherapy, the prevalence of potential neurologic symptoms from nutritional deficiencies is likely to increase. A heightened awareness of these potential complications is necessary for the appropriate care of this population.