alpha-synuclein and Sleep-Initiation-and-Maintenance-Disorders

Although resting tremor, cogwheel rigidity, hypokinesia/bradykinesia and postural instability usually dominate the clinical picture of sporadic Parkinson's disease (PD), both clinical and epidemiological data reveal that a wide variety of additional symptoms impair patients' quality of life considerably, parallel to the chronic progressive neurodegenerative movement disorder. Autopsy based retrospective studies have shown that α-synuclein immunoreactive Lewy pathology (LP) develops in the locus coeruleus (LC) of patients with neuropathologically confirmed sporadic PD, as well as in individuals with incidental (prodromal or premotor) Lewy body disease but not in age and gender matched controls. Using five case studies, this review discusses the possible role of LP (axonopathy, cellular dysfunction and nerve cell loss) in the LC, catecholaminergic tract and related circuitry in the development of PD-related dementia. The contribution of noradrenergic deficit to cognitive dysfunction in PD has been underappreciated. Noradrenergic therapeutic interventions might not only alleviate depressive symptoms and anxiety but also delay the onset of cognitive decline.

Topics: Aged; Aged, 80 and over; alpha-Synuclein; Atherosclerosis; Autopsy; Brain; Dementia; Disease Progression; Female; Humans; Lewy Body Disease; Locus Coeruleus; Male; Nerve Net; Norepinephrine; Parkinson Disease; REM Sleep Behavior Disorder; Sleep Initiation and Maintenance Disorders

Parkinson's disease is one of the most frequent progressive degenerative disorders with unknown origin of the nervous system. The commutation of the disease on Guam led to the discovery of a neurotoxin which was also found in other continents. This neurotoxin was identified in the common cyanobacteria (blue-green algae). Early clinical observations suggested some loose correlations with gastric and duodenal ulcer and Parkinson's disease, while recent studies revealed a toxin, almost identical to that found in cyanobacteria in one strain of Helicobacter pylori, which proved to cause Parkinson like symptoms in animals. Therefore, it cannot be ruled out that there is a slowly progressive poisoning in Parkinson's disease. The disease specific alpha-sinuclein inclusions can be found in nerve cells of the intestinal mucosa far before the appearance of clinical symptoms indicating that the disease may start in the intestines. These results are strengthened by the results of Borody's fecal transplants, after which in Parkinson patients showed a symptomatic improvement. Based on these observations the Parkinson puzzle is getting complete. Although these observations are not evidence based, they may indicate a new way for basic clinical research, as well as a new way of thinking for clinicians. These new observations in psycho-neuro-immunology strengthen the fact that immunological factors may also play a critical factor facilitating local cell necrosis which may be influenced easily.

Topics: alpha-Synuclein; Amino Acids, Diamino; Amyotrophic Lateral Sclerosis; Animals; Chiroptera; Cyanobacteria Toxins; Dementia; Depression; Depressive Disorder; Duodenal Ulcer; Encephalitis; Excitatory Amino Acid Agonists; Feces; Helicobacter Infections; Helicobacter pylori; Humans; Intestines; Lewy Bodies; Oxidative Stress; Parkinson Disease; Sleep Initiation and Maintenance Disorders; Stomach Ulcer

We examined 7 patients from a family harboring a novel mutation in the alpha-synuclein gene (E46K) that segregated with a phenotype of parkinsonism and dementia with Lewy bodies. An abnormal restless sleep was the presenting symptom in 2 of them. Polysomnographic (PSG) studies were performed in 4 of the 7 patients and in 2 asymptomatic carriers of the mutation. A severe loss of both rapid eye movement (REM) and non-REM sleep was observed in 2 patients complaining of insomnia and in a third parkinsonian member of the family who did not complain of trouble with sleeping. Another parkinsonian family member had a mild disorganization of the sleep architecture. The 2 asymptomatic carriers also had minor changes in the PSG findings. Episodes of bizarre behavior at night were reported historically in the 2 symptomatic patients, but we did not observed the behaviors during the PSG studies. REM sleep behavior disorder could not be recorded in any case. Our findings expand the spectrum of sleep disorders reported in synucleinopathies whether sporadic or familial.

Topics: Adult; Aged; Aged, 80 and over; alpha-Synuclein; Diagnosis, Differential; DNA Mutational Analysis; Electroencephalography; Electromyography; Electrooculography; Female; Humans; Lewy Body Disease; Male; Middle Aged; Parkinsonian Disorders; Pedigree; Point Mutation; Polysomnography; REM Sleep Behavior Disorder; Restless Legs Syndrome; Sleep Initiation and Maintenance Disorders