Dr Toshiyuki Kobayashi MD PhD, Department of Psychiatry, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke City, Tochigi 329-0498, Japan. Email: email@example.com
Creutzfeldt-Jacob disease (CJD) broadly involves the central nervous system and exhibits a wide variety of symptoms; consequently, patients are frequently misdiagnosed in its early stages with other neuropsychiatric syndromes. In the present paper, the authors report a case of CJD in a patient with alcohol dependence. A 65-year-old woman drank heavily for several years and occasionally had delusions of persecution. After a year of abstinence, she resumed drinking and exhibited behavioral anomalies. She was admitted to an internal medicine ward of a hospital because of an asthmatic attack. She then became unresponsive, bedridden and incontinent, and was moved to the psychotic ward of our hospital. From findings of rapidly progressing dementia, myoclonus, characteristic electroencephalogram, and signal increase in the cortex and basal ganglia on diffusion-weighted magnetic resonance imaging the woman was diagnosed with CJD. CJD is a rare but considerable syndrome in the differential diagnosis of alcohol-related disorders.
Creutzfeldt-Jacob disease (CJD) exhibits various symptoms with widespread involvement of the central nervous system. In the early stages, the symptoms of CJD are often similar to those of other dementias,1–4 or even of other neuropsychiatric disorders.5 Conceptually, any patient with a certain neuropsychiatric disorder can develop CJD, and it is difficult to distinguish CJD complicated with a neuropsychiatric disorder from CJD manifesting as the disorder.
In the present paper, the authors report a patient with alcohol dependence who developed CJD. Physicians misdiagnosed the patient as having an alcohol-related disorder. The patient was then moved to a psychiatric ward where she was correctly diagnosed with CJD.
A 65-year-old woman who exhibited behavioral problems during heavy alcohol use was admitted to an internal ward of a hospital because of an asthmatic attack.
The patient was married to a factory worker and had two children. She was born in the north district of Japan. At the age of 27, she moved to the capital region and began work at a chicken meat processing plant. She married a coworker at the age of 29. After the birth of her first child at the age of 32, the woman developed bronchial asthma. She quit her job at the age of 40 and took up part-time work until the age of 60. She had no record of overseas travel.
The patient was a habitual drinker. At the age of 58 she began to drink more heavily. At the age of 60 she developed bizarre behavior, for example, staying up all night to make artificial flowers to give to her colleagues. She sometimes insisted that she was maltreated at her workplace and that her husband made her coworkers harass her. On another occasion, she claimed that gangsters were watching her so she sealed up her windows.
When she quit her job, she became scared of her husband, claiming that he was going to kill her, so she fled home and stayed with her relatives for 2 months. After returning home, she was consulted to a psychiatric clinic and diagnosed with depression. She attended the clinic for 6 months. The diagnosis and treatment course at the clinic are uncertain.
For the next 3 years or so, the woman lived without any major difficulties other than drinking, episodic delusions of persecution, and forgetfulness. At the age of 62, she developed diabetes.
Without any apparent cause, the woman's alcohol intake increased. She drank approximately 2 L of beer each day and often drank all day long. Her family believed she was dependent on alcohol and attempted to take her to hospital, but failed.
At the age of 64, while attending a funeral of a relative in her hometown, she lost consciousness and was admitted to hospital. The cause of unconsciousness and details of her hospital course are uncertain. According to her family, she was in a dementia-like state, had visual hallucinations and occasionally could not recognize her family. Her blood sugar level was 565 mg/dL and brain computed tomography revealed cortical atrophy. She was hospitalized for several days. After returning home, she attended a physician's office and was treated for diabetes mellitus and bronchial asthma. She stopped drinking for a year and was able to do most of the housework.
However, after a year of abstinence, at the age of 65, the woman began to drink again. She drank approximately 3 L of beer each day, and her drunken behavior frequently became agitated. On one occasion, she became so drunk that she threatened her family with a knife and saying ‘I'll kill you’. Her alcohol intake increased along with the summer heat and her behavior became erratic, for example, she thought she was placing a pot over a fire while placing it on the kitchen table; she mimed a eating from a bowl without real chopsticks; and she could not figure out how to use the washing machine. Although her husband hid the alcohol from her, she searched for it and found it. Her husband then threw out the alcohol, so she was forced to abstain from drinking for several days and her behavior became less abnormal.
One day, several days later, she lay down from morning, complaining of listlessness. In the evening, her behavior became erratic again: she poured soy sauce on absorbent cotton and ate it, and she drank detergent. The next day, she was hospitalized because of an asthmatic attack, as well as for examination of her abnormal behavior.
Steroid therapy relieved her asthma, but her mental symptoms deteriorated soon after admission. She had hallucinations, including one of a monkey, had a resting tremor, and seemed frightened. She stayed in bed and was unresponsive. She sometimes kicked and struggled in bed, crying in fear.
Brain computed tomography revealed only mild cortical atrophy. The neurologist evaluated her as having a possible alcoholic psychosis. She was then consulted to our psychiatric clinic. Our initial impression was that she not only had an alcohol-related disorder, but that there was also an underlying organic brain disorder. We administrated diazepam at a dose of 6 mg/day, with the possibility of prolonged alcoholic withdrawal in mind. Diazepam was inefficient, so we switched to risperidone at a dose of 1 mg/day, which resulted in over-sedation. We requested a brain magnetic resonance imaging (MRI); however, it was abandoned because the patient could not keep still. At the strong demand of the physicians, the patient was moved to our psychiatric ward on her 40th day of hospitalization.
The patient was unresponsive, bedridden, and incontinent. She seemed scared and trembled all over; however, her trembling was probably myoclonus. Diffusion-weighted MRI of her brain exhibited increased signal in the frontal, parietal, and lateral cortices, and caudate nuclei (Fig. 1). Cerebrospinal fluid examination was within the normal limit. Her 14-3-3 protein level was not measured. Electroencephalogram (EEG) showed the characteristic finding of periodic sharp or biphasic and synchronous discharge (Fig. 2). Considering these findings together, she was diagnosed as having sporadic CJD.
Many reports have been published of CJD manifesting as other neuropsychiatric syndromes; however, there are only a few reports on the association between CJD and alcohol-related disorders. Gaytan-Garcia et al.6 presented a case of CJD associated with Wernicke encephalopathy. There are two reports7,8 of CJD manifesting Wernicke–Korsakoff syndrome. In contrast, Stone et al.9 reported a case of Wernicke encephalopathy manifesting variant CJD.
Although alcohol dependence associated with CJD is rare, upon first sight of the patient, we suspected that she had an unknown organic brain disorder underlying her alcohol dependence. The physicians who referred the patient to us paid insufficient attention to differential diagnosis, forejudging that she had an alcohol-related disorder.
The apparent onset of CJD in the patient was when she resumed drinking and developed behavioral problems, including miming eating from a bowl without chopsticks, and becoming confused when trying to use the washing machine. Before that, she had occasionally exhibited delusions of persecution and abnormal behavior since she was 58 years old. It is considered that her antecedent symptoms were alcohol-related and that her recent symptoms were caused by CJD. The present paper is a rare report of the comorbidity of alcohol dependence and CJD. However, the cause of the antecedent symptoms is debatable.
In the early stages of CJD, patients present mental disorders, personality changes and behavioral anomalies.10 Depression and anxiety are the most frequent symptoms.10 According to case reports of preceding depressive states before the obvious onset of CJD lasting for 2 years11 and 5 years,12 early symptoms seem to last for several years. However, it cannot be proven that these early symptoms were related to CJD. In our patient, it is difficult to detect when the early symptoms of CJD began. While the abovementioned cases showed depression, our patient had delusions of persecution, abnormal behavior and forgetfulness. Her symptoms cannot be placed in the same category with the preceding depression. They are reasonably interpreted as alcoholic psychoses or withdrawal syndromes with progressing mild alcoholic dementia, but we cannot completely deny the possibility of involvement of CJD in any way.
Our patient's resumption of drinking and the apparent onset of CJD were not coincidental; the progression of CJD could diminish suppression of drinking. If our patient did not start drinking again, the onset and deterioration of mental symptoms would come to front, and diagnosis would be easier. However, her alcohol abuse confused her family and as well as her physicians.
In our patient, brain MRI13 was useful for diagnosis along with EEG. CJD is a rare but considerable syndrome in the differential diagnosis of alcohol-related disorders.