Pick Disease Clinical Presentation

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

History

Frontotemporal lobar degeneration (FTLD) is a neuropathologic designation that encompases a group of neurodegenerative diseases of the frontal and anterior temporal lobes, associated with specific pathologies, including Pick pathology. Clinical syndromes associated with FTLD are classified under the rubric of FTD.

In FTD, the primary impairment in cognition does not involve an abnormal level of consciousness or distractibility. Such a finding is more consistent with an attentional dementia [23] or a confusional state and/or dementia. The onset of behavioral and cognitive dysfunction in individuals with Pick disease can be difficult to identify. In many cases, individuals with Pick disease perform well on quick cognitive screening tests, such as the Mini-Mental Status Examination (MMSE). [15]

Clinical features

bvFTD behavioral variant

The most common clinical subtype of FTLD is the behavioral variant frontotemporal dementia (bvFTD), which accounts for roughly more than half of FTLD cases. bvFTD is characterized by early and often severely disabling changes in personality and behavior,  which may be preceded by a long phase of subclinical behavioral changes and social disruption, often occurring in the absence of cognitive impairment. Psychiatric abnormalities that seem to respect the pattern of the classic frontal lobe syndromes are present. [24] “Possible bvFTD” criteria include only behavioral symptoms and thus bvFTD can be easily confused with psychiatric disorders.

Changes in attention, executive function, and social cognition have been reported in presymptomatic patients, especially MAPT mutation carriers. [25]

Patients with orbitofrontal dysfunction can become aggressive and socially inappropriate. Individuals become overly friendly, and may seem inappropriately explicit in their conversations.T hey become more impulsive, addiction prone, irritable, and are likely to exhibit antisocial behaviors.

Obsessive-compulsive or repetitive stereotyped behaviors may be noted. Obsessive–compulsive behavior correlates with dysfunction in networks involving orbitofrontal and anterior cingulate cortexes, basal ganglia, and thalamus.

Patients with dorsomedial or dorsolateral frontal dysfunction may demonstrate a lack of concern, apathy, or decreased spontaneity. Patients can demonstrate an absence of self-monitoring, abnormal self-awareness, and an inability to appreciate meaning. [24] They present with lack of spontaneity and motivation, which may progress to mutism and immobility in the end stages of the disease. Apathy seems to correlate anatomically with dysfunction of brain circuits involving the right anterior cingulate and caudate. Loss of empathy correlates with dysfunction in the right anterior temporal and medial frontal regions.

Patients with gray matter loss in the bilateral posterolateral orbitofrontal cortex and right anterior insula may demonstrate changes in eating behaviors, such as a pathologic sweet tooth. Patients with more focal gray matter loss in the anterolateral orbitofrontal cortex may develop hyperphagia. [26]

Though amnestic deficits are not prominent in bvFTD, in 60% of cases  patients and their caregivers report episodic memory disturbances. [27] Patients usually have relatively little limb apraxia and/or visuospatial dysfunction, thus distinguishing them from patients with diffuse, bihemispheric impairment. Cognitive symptoms of bvFTD are related to poor judgment, inattentiveness, distractibility, loss of planning ability, and disorganization. This executive dysfunction correlates with atrophy in the dorsolateral and medial prefrontal cortex.

Incontinence can occur; it tends to occur earlier as compared to Alzheimer disease.

Parkinsonism, with its concomitant history of rigidity and gait impairment, can occur. Severe or early parkinsonism indicates an alternate diagnosis, such as corticobasal ganglionic degeneration, diffuse Lewy body disease, or progressive supranuclear palsy.

Psychotic symptoms, including delusions and hallucinations, tend to occure more frequently in inherited bvFTD with MND features. [28]

svPrimary progressive aphasia

The first systematic description of a PPA case was published in 1982 by Marsel Mesulam. [29]

Age at onset of svPPA varies; commonest is between 55 and 70 years. [30]

In the semantic variant of PPA, preferential involvement of language and semantic processing is noted. A progressive loss of stored knowledge of word meaning is characteristic of svPPA, clinically evident as a multimodal loss of semantic knowledge.

Single-word naming and comprehension deficits are noted. This tends to affect low-frequency items (less familiar) in the early stages. Semantic paraphasia (e.g., clock for watch, brush for comb) are common. Anomia may be noted.

With progression, object recognition is impaired and this extends to all sensory modalities (e.g, visual agnosia). Surface dyslexia (difficulty in pronouncing irregular words, e.g, pronounce “yacht” as“yatsht”) and surface dysgraphia is noted.

Features extend beyond the realm of language. Patients may have difficulty in understanding concrete concepts. Some patients may have difficulty in facial recognition (loss of person knowledge). [31]

In mid-late phases, behavior changes may be prominent. These include disinhibition, irritability, changes in food taste, lack of empathy, and mental inflexibility. [32] Compulsive behavior is frequently seen and patients may show excessive preoccupation with normal bodily sensations. [33]

Memory impairment is relatively less severe and episodic memory tends to be better preserved. Typically, recent autobiographical memory tends to be better than remote autobiographical memory (reverse temporal gradient). [34]

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Physical Examination

The general physical examination often shows the patient to be unkempt at an earlier stage than in comparably impaired patients with Alzheimer disease.

Abnormal spontaneous behaviors observed during examination may include the following:

  • Witzelsucht or inappropriate jocularity

  • Echolalia (repeating the examiner's words), echopraxia (imitating the examiner's gestures), [35, 36] and other disinhibited approach or utilization behaviors

A general neurologic examination may include some of the following abnormalities:

  • Primitive reflexes, such as grasp, suck, and snout (not the palmomental reflex, which is often present in healthy individuals [37] )

  • Akinesia, plastic rigidity, or paratonia on motor examination [38]

  • Resting tremor - Uncommon; its presence suggests Parkinson disease or a Parkinson-plus syndrome

Mental status/neuropsychological examination may reveal the following:

  • Verbal output that is often nonfluent - Most patients have difficulty in naming common objects or pictures (anomia); spontaneous speech can be sparse, yet fluent, in character, with preserved grammar (logopenia)

  • Perseveration - Cognitive and motor (see the image below)

    Motor perseveration in a patient with Pick disease Motor perseveration in a patient with Pick disease. The patient was asked to copy loops (as demonstrated by the examiner in the first line).
  • Relatively preserved visuospatial and visual orientation skills

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