Pick Disease Workup

Updated: Jun 06, 2014
  • Author: A M Barrett, MD; Chief Editor: Jasvinder Chawla, MD, MBA  more...
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Workup

Approach Considerations

As in any dementia evaluation, initial workup includes a vitamin B-12 level, thyroid function studies, antinuclear antibodies, [15] and, possibly, fluorescent treponemal antibody testing for syphilis. The American Academy of Neurology, in their practice guidelines for the evaluation of dementia, indicates that the incidence of syphilis as a cause of dementia is so low in the typical American patient that routine screening for syphilis is not necessary. [22] However, the index of suspicion should be high in patients with human immunodeficiency virus (HIV) and in patients from geographic regions where the prevalence of syphilis is high.

If prominent inattention is observed, the patient may have a toxic and/or metabolic encephalopathy rather than a true dementia. In such patients, obtain a urine toxicology screen, serum chemistry panel, complete blood count (CBC) and differential count, liver function tests, ammonia level, and erythrocyte sedimentation rate.

If the patient has parkinsonism or a movement disorder, the following tests can be added:

  • Ceruloplasmin (serum) and serum or urinary copper to exclude Wilson disease
  • Manual peripheral blood smear for acanthocytes
  • Genetic testing - Not commercially available for screening for mutations associated with frontotemporal dementias, but genetic testing may be obtained from research laboratories.

Second-line workup

A second-line workup includes cerebrospinal fluid (CSF) examination (for chronic meningitis or elevated pressure) and HIV serology. As Alzheimer disease is almost always in the differential diagnosis, CSF analysis for Abeta1-42 may be indicated.

If prominent inattention is present, obtain a metastatic cancer workup, electroencephalogram (EEG), and Lyme disease serology. Consider consultation with a social worker, geriatric case manager, or nurse practitioner.

Third-line workup

A third-line workup includes the following:

  • Evaluation by a neuropsychologist, behavioral neurologist, or neuropsychiatrist
  • Consideration and discussion of genetic counseling and testing if a familial syndrome is suspected-- excellent information is available at Association for FTD
  • Consideration of a brain biopsy in very select patients
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CT Scanning, MRI, and PET Scanning

Brain CT scanning and MRI

Order a computed tomography (CT) scan if magnetic resonance imaging (MRI) is contraindicated in the patient (eg, if the patient has a pacemaker or metallic ocular implants).

If not contraindicated, an MRI scan is preferred. Metastatic lesions and subcortical infarction (eg, caudate, thalamic) can easily be missed on a CT scan. Frontal lobe atrophy out of proportion to atrophy in other brain regions can sometimes be detected. Some patients with frontotemporal dementia may have increased T2 signal in frontal lobe white matter, especially on fluid-attenuated inversion recovery (FLAIR) sequences. [10]

Functional brain and physiologic imaging

Functional brain imaging, eg, with single-photon emission CT (SPECT) scanning, or physiologic imaging with positron emission tomography (PET) scanning may be appropriate in some patients.

In some patients with relatively isolated social-behavioral dysfunction, employers or others may require evidence of a medical disorder. Such patients may appear cognitively normal on objective neuropsychological tests, yet may be unable to function due to acquired brain disease. A SPECT scan may demonstrate relative hypometabolism in frontal and temporal areas (when other neuroimaging is normal), thus providing evidence of brain dysfunction.

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Lumbar Puncture

Lumbar puncture (CSF examination) may be appropriate. Some memory disorder specialists perform this examination in every patient with frontal lobe or atypical dementia.

Check pressure, cultures, cryptococcal antigen, and large-volume tap for cytology or acid-fast bacillus (AFB) if the clinical situation warrants such testing. Elevated levels of phosphorylated tau protein and low levels of Abeta1-42 are found in the CSF of patients with Alzheimer disease. Data on levels of tau and beta-amyloid in CSF from patients with frontotemporal dementias has been inconsistent. [23, 24]

Markers for Creutzfeldt-Jakob disease, central nervous system (CNS) Whipple disease, progressive multifocal leukoencephalopathy, and herpes encephalitis also can be ordered from the spinal fluid.

Complications

After diagnostic lumbar puncture, some patients with Pick disease and cerebral atrophy can develop a subdural hematoma.

Observe the patient for headache or change in mental status for several days after this procedure (some physicians admit the patient for 23 h observation). If a subdural hematoma is suspected, perform a CT scan with and without contrast or an MRI scan with contrast.

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Brain Biopsy

Brain biopsy may be considered in exceptional circumstances if the diagnosis is in doubt and use of a treatment depends on the results. Occasionally, spinal fluid markers can obviate the need for a brain biopsy, even in these patients. Some of the factors mitigating for a brain biopsy include the following:

  • If the diagnosis is in doubt (eg, faced with second- or third-line autoimmune therapy for neurosarcoidosis)
  • If a familial frontotemporal dementia is suspected
  • If the family desires
  • If a treatment that has significant adverse effects is being considered

Histologic findings

Neuropathological analysis involves inspecting the morphology of neuronal or glial inclusions and their anatomical distribution. In the future, it may be important to detect FTD-tau pathology in order to administer tau-directed therapeutics. However, since FTLD-TDP is more common (about half the cases), histologic analysis is not projected to result in specific clinical decisions for most patients. Almost all cases of FTLD can be categorized as one of the above categories (FTLD-tau and FTLD-TDP) or to the molecular subgroup FTLD-FUS.

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