The neuropsychiatric symptoms associated with metabolic, endocrine, or toxic disorders (e.g., Cushing syndrome, vitamin B12 deficiency, hypercalcemia, uremia) may present difficulties in diagnosis because of the variety of clinical pictures by which they manifest themselves. Drowsiness or stupor and asterixis are the surest signs of a metabolic or drug-induced encephalopathy, but they are not always present. Psychosis with hallucinations and a great deal of fluctuation in behavior also bespeak an exogenously caused confusional state, with the exception that Lewy-body dementia also has these characteristics. Whenever any such metabolic or toxic disorder is suspected, a thorough review of the patient’s medications is crucial. Medications with atropinic activity, for example, can produce an apparent dementia or worsen a structurally based dementia, as discussed in Chap. 19. Occupational exposure to toxins and heavy metals should also be explored, but this is an infrequent cause of dementia; therefore, slight or even moderately elevated levels of these chemicals in the blood should be interpreted cautiously. It is also useful to keep in mind that seizures are not a usual component of the degenerative dementias; when they are present, they generally do not appear until a very late stage.
Once it is decided that the patient suffers from a dementing condition, the next step is to determine whether there are other neurologic signs or indications of a medical disease. This enables the physician to place the case in one of the three aforementioned categories in the bedside classification (see above and Table 20-3).
Experienced neurologists recognize that certain leading neurologic features are indicative of particular degenerative dementias. Foremost among these are disorders of movement, for example, prominent and early parkinsonian signs such as bradykinesia, tremor, and shortened step are characteristic of the subcortical dementias of Lewy body and Parkinson diseases. Rigidity of the limbs and apraxia may have a similar clinical appearance but point to corticobasal degeneration as the cause of mental decline. An early aphasia or visuospatial difficulty that is manifest as either geographic confusion or difficulty with drawing, copying, and recognizing faces and objects are characteristic of a focal degeneration of the parietal or inferior temporal lobes. Frequent falls and a disorder of vertical eye movements are the core components of progressive supranuclear palsy that often has an attendant dementia. Involuntary movements such as choreoathetosis, dystonia, ataxia, and myoclonus are each signs of particular disorders that include Huntington disease, acquired and inherited hepatocerebral degenerations, and prion disease, all of which are discussed in later chapters. In the nondegenerative categories of dementia, spasticity and Babinski signs are typical of vascular dementias.
Ancillary examinations—such as CT, MRI, lumbar puncture, measurement of blood urea nitrogen, calcium, electrolytes, and liver function tests—should be carried out in appropriate cases. Brain MRI and CT are of major importance in objectifying hydrocephalus, lobar atrophy, cerebrovascular disease, tumor, and subdural hematoma. Functional imaging, particularly with PET, including with the use of radioligands to amyloid, tau and other substances is assuming great importance in identifying Alzheimer, Lew body and corticobasal degeneration. Testing for syphilis, vitamin B12 deficiency, and thyroid function is also undertaken in many clinics almost as a matter of routine because the tests are simple and the dementias they cause are reversible. These are supplemented in individual circumstances by serologic testing for HIV infection, measurement of copper and ceruloplasmin levels (Wilson disease), heavy metal concentrations in serum, urine or tissues, autoantibodies including anti-Hu for paraneoplastic encephalitis, and drug toxicology screening. The final step is to determine, from the total clinical picture, the particular disease within each category.
(SEE ALSO CHAP. 40)