Pick's disease

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Pick's disease
ICD-10	G31.0, F02.0
ICD-9	331.11
OMIM	172700
DiseasesDB	10034
MedlinePlus	000744
MeSH	D020774

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Kalsang Dolma, M.B.B.S.[2]

Synonyms and keywords: Pick disease of brain, Wilhelmsen-Lynch Disease,Primary Progressive Aphasia, Semantic Dementia, Frontotemporal dementia

Overview

Pick's disease is a rare neurodegenerative disease. While the term Pick's disease was once used to represent a specific group of clinical syndromes with symptoms attributable to frontal and temporal lobe dysfunction, it is now used (at least among professionals in the field) to mean a specific pathology that is just one of the causes of the clinical syndrome now known as frontotemporal lobar degeneration. Some people still use the term Pick's disease to mean the more general clinical syndrome of frontotemporal lobar degeneration, but this has previously led to confusion among both professionals and patients and so its use should be restricted to the specific pathological subtype described below.

Historical Perspective

Pick's disease is named after Arnold Pick, a professor of psychiatry from the University of Prague who first discovered and described the disease in 1892 by examining the brain tissue of several deceased patients with histories of dementia. As a result, the characteristic histological feature of this disease—a protein tangle that appears as a large body in neuronal tissue—is named a Pick body. In 1911, Alois Alzheimer also noted the complete absence of senile plaques and neurofilbrillary tangles as well as the presence of Pick Bodies and occasional ballooned neurons.

Pathophysiology

Gross Pathology

Numerous different areas of the brain are affected by PiD, but the specific areas that are affected allow for differentiation between PiD and Alzheimer’s disease. Pick bodies are almost always found in several different places in the brain, including the dentate gyrus, the pyramidial cells of the CA1 sector and subiculum of the hippocampus, and the neocortex as well as a plurality of other nuclei. Interestingly, it is the location within the different layers of the brain as well as the anatomical location that demonstrates some of the unique features of PiD. A striking feature is that in the neocortex the Pick bodies are located in the II and IV layers of the cortex, which send neurons within the cortex and to thalamic synapses, respectively. While layers III and V have very few if any Pick bodies they show extreme neuronal loss that can, in some cases, be so severe as to leave a void in the brain. altogether. Other regions that are involved include the caudate, which is severely affected, the dorsomedial region of the putamen, the globus pallidus, and locus cerulus. The hypothalamic lateral tuberal nucleus is also very severely affected. The cerebellar elements that are important in receiving input, including the mossy fibers as well as the monodendritic brush cells in the granule cell layer, and generating output signals, most notably the dentate nucleus, are stricken with lots of tau protein inclusions. Strangely, the substantia nigra is most often uninvolved or only mildly involved, but cases of extreme degeneration do exist.

Microsopopic Pathology

• PiD was first recognized as a distinct disease separate from other neurodegenerative diseases because of the presence of large, dark-staining aggregates of proteins in neurological tissue as well as the aforementioned ballooned cells, which are known as Pick cells. ** Pick bodies are almost universally present in patients with PiD, but some new cases of atypical Pick’s disease have come to light that lack noticeable Pick bodies.
• A variety of stains can aid in the visualization of Pick bodies and Pick cells, but immunohistochemical staining using anti-tau and anti-ubiquitin antibodies have proven the most efficient and specific. Hematoxylin and eosin staining allows visualization of another population of Pick cells, which are both tau and ubiquitin protein negative.
• Several different silver impregnation stains have been used, including the Bielschowsky, Bodian, and Gallyas methods. The latter two techniques are sensitive enough to allow PiD to be distinguished from Alzheimer's disease as the Bodian will bind preferentially to cells with PiD as compared to the Gallyas method, which preferentially binds to the cells with Alzheimer's.** PiD has several unique biochemical characteristics that allow for unique identification of Pick’s disease as opposed to other pathological subtypes of frontotemporal lobar degeneration. The most striking of these is that this disease, which has tau protein tangles present in many affected neurons, contains only one or as many as two of the six different isoforms of the tau protein. All of these isoforms result from alternative splicing of the same gene. Pick bodies typically have the 3R isoform of tau proteins as not only the most abundant form but the only form of this protein, but a recent study has shown that a much greater number of different tau isoforms including 4R and mixed 3R/4R can be present in the Pick bodies. Not only do these tangles have the 3R tau protein predominately but they are also characteristically shaped with a round body and there is often an indentation in the area that faces the nucleus of the cell.
• The Pick bodies are also able to be labeled by N-terminal amyloid precursor protein segment, hyperphosphorylated tau, ubiquitin, Alz-50, neurofiliment proteins, clathrin, synaptophysin and neuronal surface glycoside (A2B5) specific stains. Moreover βII tubulin proteins are also suspected in playing a role in the formation of phosphor-tau aggregates that are seen in PiD as well as AD.

Causes

Whilst other pathologies causing frontotemporal lobar degeneration are associated with a genetic cause, there is no evidence in the modern literature that classical Pick's disease pathology can run in families or has a genetic cause.

Differentiating Pick's disease from Alzheimer’s disease

• The early personality changes can help doctors tell Pick's disease apart from Alzheimer’s.

Memory loss is often the main, and earliest, symptom of Alzheimer's.

• In Alzheimer’s disease, all six isoforms of tau proteins are expressed. In addition, the presence of neurofibrillary tangles that are a hallmark of Alzheimer’s can be stained with antibodies to basic fibroblast growth factor, amyloid P, and heparan sulfate glycosaminoglycan.

Natural History, Complications and Prognosis

Prognosis

• The disorder quickly and steadily becomes worse.
• Patients become totally disabled early in the course of the disease.
• Pick's disease commonly causes death within 2 - 10 years, usually from infection but sometimes from general failure of the body systems.

Complications

• Abuse by an over-stressed caregiver
• Infection
• Loss of ability to care for self or perform normal activities
• Loss of ability to interact with others
• Progressive loss of ability to function
• Side effects of medications used to treat the disorder
• Reduced life span

Diagnosis

Symptoms

• General symptoms are listed below.

• Behavioral changes:

• Can't keep a job
• Compulsive behaviors
• Inappropriate behavior
• Inability to function or interact in social or personal situations
• Problems with personal hygiene
• Repetitive behavior
• Withdrawal from social interaction

• Emotional changes:

• Abrupt mood changes
• Decreased interest in daily living activities
• Failure to recognize changes in behavior
• Failure to show emotional warmth, concern, empathy, sympathy
• Inappropriate mood
• Not caring about events or environment

• Language changes:

• Can't speak (mutism)
• Decreased ability to read or write
• Difficulty finding a word
• Difficulty speaking or understanding speech (aphasia)
• Shrinking vocabulary
• Weak, uncoordinated speech sounds

• Neurological problems:

• Memory loss that gets worse
• Weakness

• Other problems: Urinary incontinence

Physical Examination

Neurologic

• Memory loss that gets worse
• Movement/coordination difficulties (apraxia)
• Weakness
• Increased muscle tone (rigidity)
• Repeat anything spoken to them (echolalia)
• Shrinking vocabulary
• Weak, uncoordinated speech sounds

Imaging Findings

MRI

MRI scan is preferred over CT scan. 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.

Functional Brain Imaging

A Single photon emission CT scan (SPECT) may demonstrate hypometabolism in frontal and temporal areas.

Treatment

• There is no specific treatment for Pick's disease.
• It's important to treat any disorders that contribute to confusion. These may include:

• Anemia
• Decreased oxygen (hypoxia) levels
• Heart failure
• High carbon dioxide levels
• Infections
• Kidney failure
• Liver failure
• Nutritional disorders
• Thyroid disorders
• Psychiatric conditions such as depression

Medical Therapy

Sometimes patients with Pick's take the same medications used to treat other types of dementia, such as medications that decrease the breakdown of the chemical messenger, acetylcholine (anticholinesterase inhibitors), and memantine. However, there is no conclusive evidence that these help.

• Treatments for cognitive and functional losses

1. Cholinesterase inhibitors: donepezil, rivastigmine, galantamine
2. Memantine
3. Agents proposed for the treatment of cognitive decline and dementia but not recommended for routine use because adequate data are lacking or data show no benefit: aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), estrogen supplementation, alpha-tocopherol (vitamin E)

• Treatments for psychosis and agitation

1. Antipsychotic medications
2. Benzodiazepines (lorazepam, oxazepam, diazepam, clonazepam)
3. Agents proposed for the treatment of agitation in patients with dementia but not recommended for routine use because adequate data are lacking or data show no benefit: anticonvulsants, trazodone, selective serotonin reuptake inhibitors (SSRIs), lithium carbonate, beta blockers

• Treatments for depression

1. Antidepressants: cyclic antidepressants, SSRIs, and MAOIs
2. Dopaminergic agents such as psychostimulants
3. Electroconvulsive therapy (ECT)

• Treatments for sleep disturbance

1. Trazodone, zolpidem, zaleplon
2. Benzodiazepines, diphenhydramine, antipsychotics

Psychotherapy

• Behavior-oriented approaches
• Stimulation-oriented approaches (e.g., recreational activities or therapies, music therapy, dance therapy, art therapy, exercise, multisensory stimulation, simulated presence, aromatherapy)
• Emotion-oriented approaches (e.g., supportive psychotherapy, reminiscence therapy, validation therapy, sensory integration, and simulated presence therapy)
• Cognition-oriented approaches (reality orientation, cognitive remediation, and skills training)

Family Counselling

• Depending on the symptoms and severity of the disease, the patient may need monitoring and help with personal hygiene and self-care. Eventually, there may be a need for 24-hour care and monitoring at home or in a special facility.
• Family counseling can help the person cope with the changes needed for home care.