2062
Synucleinopathies refers to neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibers or glial cells.
Synucleinopathies are characterized by the deposition of phosphorated alpha-synuclein within the CNS and peripheral nervous systems.
There are three main types of synucleinopathy: Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA): pure autonomic failure is an additional type.
All four synucleinopathies have overlapping clinical features, characterized by progressive neurodegeneration and disability.
In pure autonomic failure, Parkinson’s disease, and dementia with Lewy bodies, Lewy body deposition in various peripheral and central structures occur.
In multiple system atrophy alpha-synclein deposition in glial cells termed cytoplasmic inclusions occur.
Other rare disorders, such as various neuroaxonal dystrophies, may have α-synuclein pathologies.
The synucleinopathies have features of parkinsonism, impaired cognition, sleep disorders, and visual hallucinations.
They can sometimes overlap with tauopathies.
REM sleep behavior disorder (RBD) is a parasomnia.
In REM sleep behavior disorder individuals lose atonia that is normal during rapid eye movement (REM) sleep, and act out their dreams or have other abnormal movements or vocalizations.
Abnormal sleep behaviors may appear decades before any other symptoms, in synucleinopathy.
On autopsy, 94 to 98% of individuals with polysomnography-confirmed REM sleep behavior disorder are found to have a synucleinopathy—most commonly with dementia with Lewy bodies or Parkinson’s disease.
A high proportion of individuals with this group of neuro degenerative disorders have a positive skin biopsy test for phosphorylated alpha-synuclein (>90%) and may help in the diagnosis.
Symptoms of the specific synucleinopathy usually manifest within 15-50 years of the diagnosis of REM behavior sleep disorder.
Alpha-synuclein deposits occur in the cardiac muscle and blood vessels.
Patients with synucleinopathies have cardiovascular dysfunction, but most are asymptomatic.
Alpha-synuclein deposits affect every level of gastrointestinal tract.
Symptoms related to Alpha-synuclein deposits in the upper gastrointestinal tract cause dysfunction such as delayed gastric emptying or lower gastrointestinal dysfunction, such as constipation and prolonged stool transit time.
Patients suffering with synucleinopathies are subject to: Urinary retention, waking at night to urinate, increased urinary frequency and urgency, and over or underactive bladder.
Sexual dysfunction including erectile dysfunction, and difficulties achieving orgasm or ejaculating may appear early in the course of asynucleinopathy.