Perry syndrome

Radiopaedia • CC-by-nc-sa 3.0 • de

Perry syndrome is a rare, progressive, hereditary neurodegenerative movement disorder and TDP-43 proteinopathy.

Epidemiology

Perry syndrome is considered to be very rare, generally isolated to select families who carry the mutation implicated in the disease . In one study, the age on onset was found to be approximately 50 years, with a range of 35-70 years .

Clinical presentation

Perry syndrome is classically characterized by :

  • parkinsonism: rigidity, tremor, bradykinesia, and postural instability
  • psychiatric symptoms: apathy and depression
  • respiratory compromise: central hypoventilation and central sleep apnea
  • weight loss: unintentional and progressive in nature

In addition to these features, patients many have a wide array of other neurological symptoms, such as presence of frontal signs, oculomotor disorders, dysphagia, dementia, and autonomic dysfunction .

Pathology

Perry syndrome is an autosomal dominant disorder, caused by mutation to the DCTN1 gene, on chromosome 2p13.1. The DCTN1 gene encodes for dynactin-1, which plays a vital role in transport of materials within neurons . In Perry syndrome, this process is impaired, resulting in progressive neuronal loss. In particular, neuronal loss is most marked in the substantia nigra . However there is also involvement in other parts of the central nervous system, such as other regions of the basal ganglia and brainstem, with notable sparing of the cortex . Progressive neuronal loss in these regions results in the described clinical phenotype.

Microscopic appearance

Affected regions of the brain in Perry syndrome unsurprisingly demonstrate neuronal loss and gliosis . Furthermore, on immunostaining, neurons may have abnormal transactive response DNA-binding protein of 43 kDa (TDP-43)-positive cytoplasmic inclusions . Thus, Perry syndrome is considered a TDP-43 proteinopathy.

Radiographic features

Neuroimaging in Perry syndrome is often unremarkable, however there may be some subtle changes in patients with certain clinical features . For example, MRI brain may reveal frontotemporal atrophy, which may be more likely to be present in patients with Perry syndrome with concurrent frontal signs . Similarly, in patients with concurrent oculomotor signs, there may be midbrain atrophy noted .

Treatment and prognosis

Management of Perry syndrome is symptomatic, such as trialing levodopa therapy for parkinsonism, and managing respiratory symptoms with non-invasive ventilation or diaphragmatic pacemaker insertion .

Unfortunately, Perry syndrome is a progressive condition that is ultimately fatal, often due to respiratory complications, with one study finding a median disease duration of 5 years .

History and etymology

The syndrome was first described in a Canadian family by Thomas L Perry and colleagues in their 1975 seminal case series .

Differential diagnosis