Which of the following CSF studies would be most helpful in supporting the probable diagnosis? A 49-year-old female physician has a 2-month history of increasing forgetfulness, difficulty reading, loss of interest in her appearance, and walking with a jerky, wide-based gait. She has been unable to work for several weeks. Her past medical history is unremarkable, and she takes no medications. Family medical history is noncontributory.\nÂ Â Â Â On physical examination, the patient is alert but is uncommunicative and uncooperative. There is bilateral horizontal nystagmus and decreased visual acuity. The gait is wide-based and ataxic. A prominent resting tremor of the hands is noted. Motor strength is good throughout, but several myoclonic jerks of the upper and lower extremities are noted. A lumbar puncture is performed. The only abnormal CSF finding is a protein of 98 mg/dL.
A. VDRL test for syphilis B. Measurement of amyloid-Î² C. Measurement of 14-3-3 protein D. Measurement of microtubule-associated protein tau E. Histologic examination for Negri bodies
Elevated amounts of 14-3-3 proteins are found in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.
14-3-3 proteins are a family of conserved regulatory molecules expressed in all eukaryotic cells.
14-3-3 proteins have the ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and transmembrane receptors. More than 100 signaling proteins have been reported as 14-3-3 ligands.
The name 14-3-3 refers to the particular elution and migration pattern of these proteins on DEAE-cellulose chromatography and starch-gel electrophoresis. The 14-3-3 proteins eluted in the 14th fraction of bovine brain homogenate and were found on positions 3.3 of subsequent electrophoresis by Moore and Perez (1967).
The first symptom of CJD is rapidly progressive dementia, leading to memory loss, personality changes and hallucinations. This is accompanied by physical problems such as speech impairment, jerky movements (myoclonus), balance and coordination dysfunction (ataxia), changes in gait, rigid posture, and seizures. The duration of the disease varies greatly, but sporadic (non-inherited) CJD can be fatal within months or even weeks (Johnson, 1998). In some people, the symptoms can continue for years. In most patients, these symptoms are followed by involuntary movements and the appearance of an atypical diagnostic electroencephalogram tracing. Most victims die six months after initial symptoms appear, often of pneumonia due to impaired coughing reflexes. About 15% of patients survive two or more years.
The symptoms of CJD are caused by the progressive death of the brains nerve cells, which is associated with the build-up of abnormal prion proteins forming amyloids. When brain tissue from a CJD patient is examined under a microscope, many tiny holes can be seen where whole areas of nerve cells have died. The word spongiform in transmissible spongiform encephalopathies refers to the sponge-like appearance of the brain tissue.