Psychosomatics 40:260-263, June 1999
© 1999 The Academy of Psychosomatic Medine
The Varied Neuropsychiatric Presentations of Creutzfeldt-Jakob Disease
Chris K. Moellentine, M.D., and
Teresa A. Rummans, M.D.
Received May 29, 1998; revised October 16, 1998; accepted October 23, 1998. From the Department of Psychiatry, Mayo Clinic, Rochester, Minnesota. Address reprint requests to Dr. Rummans, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905.
Key Words: Neuropsychiatric Disorders • Creutzfeldt-Jakob Disease
Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative dementing illness with an incidence of roughly one case per million annually. CJD results from a prion infection of the central nervous system with both cortical and subcortical manifestations.
Prion diseases, also referred to as spongiform encephalopathies because of their characteristic pathologic appearance, include several human diseases with CJD being the most common.1 A prion is a protein that acts as the infectious agent, differing from a virus as it does not include any nucleic acid. CJD mainly occurs sporadically but is both heritable and transmissible,1 although the mode of transmission is unknown. Ten to fifteen percent of cases occur in a familial pattern. Human-to-human transmission is rare with only iatrogenic cases being reported.
Clinically, CJD usually occurs in middle or late life with a few reports of younger presentations. Clinical features are quite varied, as outlined in Table 1,2 but often include dementia, disturbances of gait, incoordination, rigidity, and myoclonus. The onset of illness may be gradual, but the progression of disease is rapid, ending in death usually within 1 year.
Diagnosis of CJD may be difficult, with routine blood counts, chemistries, and cerebrospinal fluid (CSF) usually being normal. Both CT and MRI may be normal or reveal cerebral atrophy late in the course of the disease. Classic EEG changes are those of periodic (1–2 cycles/second) discharges of large (triphasic) sharp wave or "burst suppression" high-voltage activity.2 Although EEG is generally considered a useful tool for the diagnosis of CJD, some cases have been reported where the EEG is nonspecific.3 CSF evaluation may reveal CJD-specific proteins or genetic testing may reveal mutations in the prion protein.4 However, neither of these evaluations is routinely performed and they are difficult to obtain. Pathologic examination reveals a degenerative picture with gross atrophy, neuronal loss, gliosis, and vacuoles developing in neurons, giving a characteristic spongy appearance.
There have been only a few case reports5–7 with little attention in the literature given to the psychiatric manifestations of CJD. In fact, there is a well-described prodromal phase of the disease in which symptoms may be vague and can include weight loss, fatigue, dizziness, headache, disorders of sleep, impaired judgment, and unusual behavior.1 An unusually intense emotional response to the environment as well as delusions, hallucinations, and agitation may be interpreted as a depressive or psychotic illness.8 In review of 232 experimentally transmitted cases of sporadic CJD, approximately one-third of the cases at the outset manifested mental deterioration only, with some form of "emotional abnormality" found in the majority of cases.5 Ten percent of patients with CJD are admitted to psychiatric wards.6
The following case illustrates how diagnosing CJD is difficult for psychiatrists, neurologists, and internists alike because of the variability and complexity of its presentation.
Case Report
Mr. C., a 40-year-old married father of two who worked as a consultant in a computer firm, was admitted for evaluation of progressive confusion, bizarre, unpredictable behavior, and aggression.
Mr. C., who had no previous medical or psychiatric history or family psychiatric history, was noted by his wife to have a change in his personality and a decline in his level of functioning 1 year prior to admission. Personality changes including paranoia and irritability led to significant marital discord during that year. They had received marital therapy during which time it was revealed that they had been involved in extramarital affairs. The patient further reported a history of an incestuous relationship with his mother between the ages of 10 and 15, for which he felt quite guilty and remorseful. This history was questioned and refuted by his wife and family.
Initially Mr. C.'s wife noticed that his sleep was restless. Later, his thoughts and behavior became erratic. He became increasingly dependent on his wife, often going to work with her. At other times he became paranoid and believed his wife was trying to poison him, causing him to flee from her. He described visual hallucinations of people coming into their house.
Mr. C. became hypersexual, wanting intercourse three to four times per day. He believed certain parts of his body were numb, including his genitalia. He would wash his penis excessively to the point of abrasions.
Mr. C. began complaining of daily headaches, occasional blurred or double vision with scintillations. He was moody, irritable, and aggressive. His oral intake decreased and he lost 40 pounds. He developed episodic confusion, difficulty concentrating and reading, and memory impairment. He could no longer work and he withdrew from family and friends.
At the time of admission, he was anxious and restless. His affect was flat. He appeared depressed. His thought processes were tangential. He was paranoid and was believed to be experiencing visual hallucinations, which he denied. He denied suicidal or homicidal thinking. Cognitively he was impaired with an MMSE score of 10/30.
His initial neurologic examination was remarkable for an inconsistent widebased and staggering gait. There was a variable resting and action tremor involving the arms, trunk, and head that would escalate when startled and improve when distracted. Muscle strength and tone were normal, deep tendon reflexes hypoactive, and plantar responses were downgoing. There were no fasciculations, dystonic movements, or myoclonic jerks. Cranial nerves as well as sensory and cerebellar systems were intact.
During a previous hospitalization elsewhere (and initially here), Mr. C.'s extensive medical and neurologic workups were unremarkable. Workups included complete blood count, electrolytes, sedimentation rate, thyroid-stimulating hormone, serum creatinine, glutamate oxaloacetate transaminase, syphilis serology, antinuclear antibody, serum copper, ceruloplasmin, and HIV titre. Urinalysis, chest x-ray, electrocardiogram, CT abdomen, MR head, EEG, CSF evaluation, cerebral angiogram, and urine screen for heavy metals were also unremarkable.
After both negative medical and neurologic evaluations, those caring for him believed his symptoms were the result of a severe psychiatric disorder. Our initial differential diagnoses included a conversion disorder; factitious disorder; major depression with psychotic features; bipolar disorder, NOS; and psychosis, NOS.
Hospital Course. Mr. C.'s presentation and clinical course were inconsistent and fluctuated over time. He clenched his fists with anger and frustration, rubbing his hands through his hair and furrowing his brow. At other times he smiled and laughed inappropriately stating "I am doing ridiculous things" while hiding from a nurse. He assumed dramatic and bizarre postures. He slept poorly and was restless at night, wandering around the unit. He was intrusive and needed constant redirection. There were episodes when he would disrobe and urinate on the floor. He was alert but was grossly disoriented. He exhibited hypervigilance with an exaggerated startle response. His affect was labile, anxious, and intense. His speech was monotonous and slowed with a paucity of content and perseveration, seeming vague and avoidant, answering "I don't know" to many questions. At times he was thought blocking.
Extensive evaluations were again nonrevealing except for a SPECT scan that showed left frontal, left temporal, and biparietal hypoperfusion and an EEG showing diffuse slow wave abnormalities consistent with an organic encephalopathy. Neuropsychological testing when compared with previous studies showed a progression of cognitive decline across virtually all levels of function with significant comment on variable level of attention and concentration. On projectives, Mr. C.'s responses were bizarre and characterized by unusual personalizations and excessive affect, responding to the cards as if they were real. He would grab the ink blot and ask "Is my wife in there?"
Early in the course of his illness, work and family stresses were believed to have contributed to his clinical picture. Consequently, Mr. C. received individual and marital counseling. Later, as the illness progressed, various psychotropic medications including antipsychotics (haloperidol and risperidone), antidepressants (trazodone), benzodiazepines (lorazepam), and mood stabilizers (valproic acid and carbamazepine) as well as ECT with eight bilateral treatments were administered with only fleeting improvement or transient worsening of symptoms noted. Ultimately the patient was discharged to a long-term care facility with the diagnosis of a neurodegenerative process of unknown etiology. He continued to have a declining course. He became mute, wheelchair bound, and unable to feed himself. He developed occasional myoclonic jerks and increased muscle tone. He went into a nearly vegetative state several months later and died within 1 year. At autopsy his brain had extensive spongiform changes consistent with the diagnosis of CJD.
Discussion
Initially, Mr. C.'s history was confusing and misleading as it was discovered later that the accusations made by the patient toward his wife and parents were false. Conflicts with his wife stemmed from his significant personality changes. The inconsistent and fluctuating clinical presentation led one to initially consider the gamut of psychiatric disorders producing his illness. The presence of significant abnormalities detected by SPECT led those caring for Mr. C. to seriously consider an undiagnosed neurological disorder for the cause of his bizarre, progressive, neuropsychiatric decline. Indeed, several case reports have demonstrated that, especially in the atypical presentation (i.e., nonspecific EEG change or absence of myoclonus), SPECT may provide useful, although not diagnostic, information.9,10
How atypical for CJD was Mr. C.'s presentation? This patient had subacute onset of an atypical dementia with total course lasting approximately 3 years. This is commonly associated with CJD. However, our patient had nonspecific EEG changes and no observed myoclonus. It has been reported that patients in early stages of CJD may have normal or show nonspecific changes on EEG,2 with up to 60% failing to ever demonstrate the classic findings. Myoclonic jerks found in CJD are often precipitated by environmental or physical stimuli,11 giving the impression of an exaggerated startle response.8 In fact Mr. C. was given a trial of beta blockers for a striking startle reflex.
Significant truncal ataxia and upper extremity tremors were also a prominent part of the clinical presentation, which was often referred to as an astasia-abasia. Sethi and Hess11 state that the differential diagnosis of an otherwise obscure movement disorder should include CJD even in the absence of a typical EEG pattern. Other atypical dementias such as Gerstmann-Sträussler-Scheinker syndrome are rare. This syndrome is associated with a strong family history, which our patient did not have, and a longer course of illness.4,12
Mr. C.'s case is one in which the salient features of the clinical presentation were psychiatric. It is known that behavioral or functional disturbance may occur as the dominant or even sole manifestation of a viral infection in the brain. K. Kristensson13 reviewed potential pathogenic mechanisms by which viruses produce behavioral disturbances. These include alterations in neuronal structure (i.e., synaptic receptors and ion channels), function, and the extra and intraneuronal milieu in which the neurons are immersed. Although prions differ from the viruses, these changes may be similarly found and produce similar mechanisms by which prions produce psychiatric symptoms in patients affected with CJD.
In conclusion, psychiatric cases that are complex with contradictory history and physical findings and do not respond to or are refractory to typical treatment modalities should be frequently reassessed for presence of an occult medical or neurologic condition such as CJD. Further, if appropriate, it is important that at least an index of suspicion be maintained for neurodegenerative diseases such as CJD even if classic signs and symptoms such as myoclonus or classic EEG changes are absent. CJD may be one disease with a single pathogenesis, but its presentation often occurs in a kaleidoscopic fashion.
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