Hideki Onishi

Successful treatment of Wernicke encephalopathy in terminally ill cancer patients: Report of 3 cases and review of the literature

Although Wernicke encephalopathy has been reported in the oncological literature, only one terminally ill cancer patient with Wernicke encephalopathy has been reported. Wernicke encephalopathy, a potentially reversible condition, may be unrecognized in terminally ill cancer patients. In this communication, we report three terminally ill cancer patients who developed Wernicke encephalopathy. Early recognition and subsequent treatment resulted in successful palliation of delirium. Two of the three patients did not show the classical triad of Wernicke encephalopathy. Common clinical symptoms were delirium and poor nutritional status. Intravenous thiamine administration dramatically improved the symptoms of delirium in all three patients. In terminally ill cancer patients, clinicians must remain aware of the possibility of Wernicke encephalopathy when patients with a poor nutritional status present with unexplained delirium. Early intervention may correct the symptoms and prevent irreversible brain damage and the quality of life for the patient may improve.

Effects of CYP2D6 polymorphisms on neuroleptic malignant syndrome

ObjectiveNeuroleptic malignant syndrome (NMS) is one of the most serious adverse reactions to antipsychotic medications. We accumulated data on Japanese NMS patients and, in a study designed to examine the effects of drug metabolism on the occurrence of NMS, tested the possibility of association between NMS and CYP2D6 polymorphisms.MethodsWe studied 53 patients who had experienced NMS and 112 healthy individuals. We determined what drugs the patients with NMS had been given and retrospectively identified candidates for drugs causing NMS. We screened the prevalence of CYP2D6 genotypes using polymerase chain reaction and restriction fragment length polymorphism analyses.ResultsThe prevalence of *5 alleles in the group of all patients with NMS was higher than that in the controls, though this difference was not statistically significant (10.4% vs. 5.4%; P = 0.107; odds ratio (OR) 2.05; 95% confidence interval (CI) 0.87–4.80). No association was found between the frequency of *10 alleles and the occurrence of NMS. We found *4 and duplicated alleles in only one patient each among the patients with NMS. A total of 29 patients appeared to have developed NMS as a result of having taking CYP2D6 substrates. The prevalence of *5 alleles in these 29 patient was significantly higher than that in the controls (15.5% vs. 5.4%; P = 0.020; OR 3.25; 95% CI 1.30–8.13).ConclusionOur findings suggest that the CYP2D6*5 allele is likely to affect vulnerability to development of NMS.

Characteristics, interventions, and outcomes of misdiagnosed delirium in cancer patients.

OBJECTIVE Although delirium is a common psychiatric complication in cancer patients, it is often not accurately recognized. To date, the characteristics and outcome of misrecognized patients are unclear in the cancer setting. This retrospective study was planned to determine the recognition by oncologists at the psychiatric consultation, characteristics, reversibility and outcome of misrecognized patients with delirium. METHOD We reviewed charts of 60 patients diagnosed with delirium by the psycho-oncologists who were referred to the psychiatric consultation by the oncologists. Information about demographics, initial assessment by the oncologists, delirium subtype, precipitating factors, intervention for delirium, reversibility, and final status was obtained. RESULTS Twenty-two among 60 delirious patients were misrecognized by the oncologists at the time of consultation. They were often diagnosed as having anxiety or other psychiatric disorders. Misrecognized participants were significantly younger than accurately recognized cases of delirium. The psychiatrists made suggestions to the oncologists for all the referred patients, even when they were accurately diagnosed with delirium before consultation. For the correctly recognized patients, the main suggestion was pharmacological reevaluation. For the misdiagnosed cases, the psychiatrists suggested a reconsideration of the strategy for cancer treatment and the provision of information to the patients family members about their condition. SIGNIFICANCE OF RESULTS Despite its high prevalence, delirium is difficult to diagnose for non-psychiatric physicians. Its detection is important not only to give the best treatment option to cancer patients but also to provide the best opportunity to inform their family about their condition and end-of-life issues.

Lack of association in Japanese patients between neuroleptic malignant syndrome and a debrisoquine 4-hydroxylase genotype with low enzyme activity.

Decreased activity of debrisoquine 4-hydroxylase (CYP2D6), which participates in hepatic metabolism of several frequently used neuroleptics and antidepressants, is inherited as an autosomal recessive trait through polymorphic CYP2D6 gene alleles. In eastern Orientals, a C --> T substitution at nucleotide 188 (Pro34Ser) is primarily responsible for decreased ability to metabolize CYP2D6 substrates. We therefore studied a possible association between neuroleptic malignant syndrome (NMS) and the C188T mutation. We examined the frequency of the C188T mutation by polymerase chain reaction and restriction fragment length polymorphism analysis in 36 Japanese patients previously diagnosed with NMS and 107 neuroleptic-treated schizophrenic patients with no NMS history. The C188T allele frequency was 0.417 in NMS patients and 0.463 in patients without NMS. No significant allele or genotype associations were observed. We cannot conclude that low CYP2D6 activity genotype causes susceptibility to NMS in Japanese patients.

Wernicke encephalopathy presented in the form of postoperative delirium in a patient with hepatocellular carcinoma and liver cirrhosis: a case report and review of the literature.

OBJECTIVE Although Wernicke encephalopathy has been reported in the oncological literature, it has not previously been reported in postoperative cancer patients. METHODS In this communication, we report a patient of hepatocellular carcinoma with liver cirrhosis who developed Wernicke encephalopathy in the form of postoperative delirium. Preoperatively, the patient had a very good appetite and had eaten all the food of an 1800 cal/day diet until 1 day before operation. The operation was done without any complications. The patient developed delirium 2 days after the lobectomy of the liver. The level of delirium remained unchanged until administration of thiamine starting on day 7 postoperatively, which resulted in palliation of delirium without brain damage. Laboratory data demonstrated that the serum thiamine level at day 6 postoperatively was below the lower limit of normal. As the mechanism of Wernicke encephalopathy, we thought that decreased ability to store thiamine due to liver cirrhosis led to depletion of thiamine faster than had been expected. RESULTS AND SIGNIFICANCE OF THE RESEARCH In cancer patients, clinicians must always remain aware of the possibility of Wernicke encephalopathy, especially in patients with liver dysfunction, which decreases the ability to store thiamine in the liver. Early detection and intervention may alleviate the symptoms of delirium and prevent irreversible brain damage.

Development of Wernicke encephalopathy in a terminally ill cancer patient consuming an adequate diet: A case report and review of the literature

Malignancy-associated primary thiamine deficiency has been documented in several experimental tumors, clinical case reports, and in patients with fast growing malignancies. We report a terminally ill cancer patient who developed delirium. Close examination of the patient demonstrated that delirium was caused by thiamine deficiency, although she had been consuming an average of 990 cal/day for the past 3 weeks. Malabsorption or consumption by the tumor was considered the mechanism of thiamine deficiency. Early recognition and subsequent treatment resulted in successful palliation of delirium. In terminally ill cancer patients, clinicians must remain aware of the possibility of Wernickes encephalopathy, when the patients develop unexplained delirium, even if the patient has been consuming adequate amounts of food. Early intervention may correct the symptoms and prevent irreversible brain damage, and the quality of life for the patient may improve.

Neuroleptic malignant syndrome and hydroxylase gene mutations: no association with CYP2D6A or CYP2D6B.

To examine a possible association between debrisoquine 4-hydroxylase gene mutations and neuroleptic malignant syndrome, we assessed frequencies of wild type and A and B mutant alleles of the CYP2D6 gene in 24 patients with a history of nuroleptic malignant syndrome, 50 patients with neuroleptic-treated schizophrenia but no history of neuroleptic malignant syndrome, and 50 healthy controls. Allele frequencies did not differ significantly between these groups. Homozygotes for CYP2D6A and for CYP2D6B, which indicate a poor-metabolizer phenotype for the CYP2D6 substrate, were not detected among the neuroleptic malignant syndrome cases. This result indicates no excess of poor CYP2D6 metabolizers in neuroleptic malignant syndrome. The aetiology of neuroleptic malignant syndrome is not explainable in terms of CYP2D6 gene mutations.

Psychiatric Disorders in Cancer Patients at a University Hospital in Japan: Descriptive Analysis of 765 Psychiatric Referrals

OBJECTIVE In cancer patients, adjustment disorders, delirium and depression have been identified as common psychiatric disorders. Although a comparable result was reported in the National Cancer Center in Japan, the nature of patients in that hospital may differ from that in local hospitals. There is a possibility to expand the findings of psycho-oncology by evaluation of the data from a local university hospital and comparison with the National Cancer Center data. METHODS We retrospectively reviewed the medical records of cancer patients who were referred to the Department of Psycho-Oncology at Saitama Medical University International Medical Center. We identified their characteristics and psychiatric diagnoses and compared these with the National Cancer Center data. RESULTS During the study period, 765 cancer patients were referred. The numbers of inpatients and outpatients were almost the same. The most common psychiatric diagnosis was adjustment disorders (24%), followed by delirium (16%) and then major depressive disorder (12%). The rank of these three was the same as that at the National Cancer Center. Outpatients constituted more than 80% of the patients with major depressive disorder. The proportion of cancer patients with schizophrenia in this study (4.3%) was higher than that in the National Cancer Center (1.6%). CONCLUSIONS This study revealed basic information about the consultation data of cancer patients at a local university hospital in Japan. The importance of communication with outpatients was suggested. It seems that cancer treatment for patients with schizophrenia in a local hospital is also important.

Detection and treatment of akathisia in advanced cancer patients during adjuvant analgesic therapy with tricyclic antidepressants: Case reports and review of the literature

OBJECTIVE There is substantial evidence that tricyclic antidepressants are effective in the management of chronic pain, including cancer pain. In oncological settings, these agents are used as adjuvant analgesic drugs. However, cases of akathisia due to tricyclic antidepressants used as adjuvant analgesic therapy have not previously been reported. CASE REPORTS Two cancer patients experiencing chronic pain who were refractory to nonsteroidal anti-inflammatory drugs and opioids were prescribed amoxapine as an adjuvant analgesic therapy for neuropathic pain. These patients developed inner restlessness and restless physical movements after amoxapine was prescribed. Although symptoms were atypical, akathisia was suspected and discontinuation of amoxapine resolved the symptoms. RESULTS AND SIGNIFICANCE OF RESULTS Akathisia should be considered in patients receiving adjuvant analgesic therapy with tricyclic antidepressants. Early detection and appropriate treatment will relieve this distressing symptom. Restless movements involving parts of the body other than the legs may be the clue to the diagnosis.

The evaluation of the relationship between the level of disclosure of cancer in terminally ill patients with cancer and the quality of terminal care in these patients and their families using the Support Team Assessment Schedule.

Aims: To examine the relationship between informing patients of cancer and the quality of terminal care. Methods: This was a study of 87 consecutive terminally ill cancer patients who died during the last 27-month period. Notification of cancer was classified into 4 groups (A, B, C, and D, respectively): “nondisclosure,” “disclosure of cancer diagnosis,” “disclosure of life threatening,” and “disclosure of poor prognosis.” We evaluated the quality of palliative care using Support Team Assessment Schedule–Japanese (STAS-J). Results: A, B, C, and D groups included 8, 22, 37, and20 cases, respectively. Regarding physical symptoms, no marked difference was noted. Anxiety was significantly reduced, and the recognition of disease conditions and the level of communication were significantly higher in the groups that received specific information (P < .001). Conclusions: Informing patients of more specific information will increase the quality of terminal care.