Pick Disease Workup

Updated: Nov 18, 2019
  • Author: Monica Saini, MD, MBBS, MRCP(UK); Chief Editor: Jasvinder Chawla, MD, MBA  more...
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Workup

Approach Considerations

As in any dementia evaluation, initial workup includes avitamin B-12 and folic acid levels, thyroid function studies, antinuclear antibodies, [23] and fluorescent treponemal antibody testing for syphilis. The American Academy of Neurology, in their practice guidelines for the evaluation of dementia, indicate that the incidence of syphilis as a cause of dementia is low in the typical American patient and that routine screening for syphilis is not necessary. [41] 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. 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 observed, the patient may have a toxic and/or metabolic encephalopathy rather than a true dementia. In such patients, and also in patients with a rapid onset or progression of cognitive complaints, obtain a urine toxicology screen, serum chemistry panel, complete blood count (CBC) and differential count, liver function tests, ammonia level, and erythrocyte sedimentation rate. Malignancy workup, electroencephalogram (EEG), and Lyme disease serology may be indicated in select cases.

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

  • 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. Consideration and discussion of genetic counseling and testing may especially be relevant in patients where family history suggestive of genetic taupathy is obtained (dementia, behavior disturbance, motor neuronopathy, parkinsonism, or a combination of these syndromes in >1 relative, one of whom is a first-degree relative).

Excellent information is available at Association for FTD.

All patients suspected to have Pick disease require a detailed cognitive assessment.  Evaluation by a neuropsychologist, behavioral neurologist, or neuropsychiatrist may be needed.

  • Language assessment: For svPPA, tests include confrontational naming (e.g, Boston Naming test), tests of semantic association (e.g., Pyramids and Palm Trees test), and knowledge (e.g, naming famous faces), reading and spelling of irregular words, evaluation of spontaneous speech, repetition and syntactic comprehension.

  • Frontal lobe function should be assessed in all patients suspected with Pick disease.

  • Characteristic behavioral features in bvFTD patients may be measured with scales such as frontal behavioral inventory (FBI), neuropsychiatric inventory (NPI), and Cambridge behavioral inventory (CBI). Neuropsychological tools such as theory of mind (ToM) tasks and social cognition and emotional assessment (SEA) have been demonstrated to be able to detect and distinguish bvFTD at an early stage from Alzheimer’s disease (AD). [42]

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Imaging Studies

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. 

Typically, semantic impairment is associated with greater left-sided anterior temporal atrophy. Naming difficulties are correlated with involvement of the superior portions of the left temporal pole, while loss of person knowledge and behavioral changes are associated with more extensive right temporal atrophy. PPA appears to be associated not only with grey matter but also with significant white matter degeneration. [43]

Patients with FTD show earliest structural changes in the insula and temporal and frontal areas. They may have increased T2 signal in frontal lobe white matter, especially on fluid-attenuated inversion recovery (FLAIR) sequences. [14]

 

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.

Semantic impairment is associated with greater left-sided anterior temporal  hypometabolism-on fluorodeoxyglucose (FDG) PET. [44] In these patients, resting-state functional magnetic resonance imaging has shown decreased functional connectivity along the ventral language pathway and increased functional connectivity along the dorsal language pathway, [45] which corresponds well with the clinical deficits in this syndrome. In patients with svPPA, a decrease in Fractional Anisotropy has been demonstrated in the longitudinal, uncinate, cingulum, and external capsule fasciculi. [46]

In patients with bvFTD, uni- or bilateral hypometabolism is noted in the prefrontal cortex, anterior temporal lobe, anterior cingulate, and basal ganglia (FDG PET). [47]

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Lumbar Puncture

Lumbar puncture (CSF examination) is performed in patients with atypical features or rapidly progressive cognitive impairment. Cerebrospinal fluid is usually examined for cell count, protein, cryptococcal antigen, acid-fast bacillus (AFB), cultures, VDRL, and cytology,  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. [48, 49] Studies have suggested that FTLD patients (including bvFTD) display higher levels of CSF NfL and/or lower ratio of phospho-tau/tau compared to healthy controls or patients with other neurodegenerative or psychiatric diseases, including, for example, AD. [50] However, there are no routinely used or guideline-mandated CSF biomarkers for the diagnostics of bvFTD or svPPA. 

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. Indication for such tests is determined by the clinical picture and differentials being considered for an individual patient.

Complications

Headache is the commonest complication following LP, and tends to self-resolve within 24–48 hours. Symptomatic intracranial hypotension, secondary to a persistent CSF leak, is less common and may in rare cases be complicated by development of subdural hematomas.

Observe the patient for headache or change in mental status for several days after this procedure (some physicians admit the patient for 23-hr observation). If patient has persistent headache, signs of low intracranial pressure, or you suspect a subdural hematoma, 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. Usually, this occurs in setting of atypical features or a very rapid progression, where treatable pathologies need exclusion. 

Occasionally, spinal fluid markers can obviate the need for a brain biopsy, even in these patients.

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