Lewy body constipation

Sakakibara R1, Tateno F1, Aiba Y1, Yamamoto T2, Uchiyama T3, Yamanishi T4, Panicker J5

Research Type

Clinical

Abstract Category

Anorectal / Bowel Dysfunction

Abstract 92
E-Poster 1
Scientific Open Discussion ePoster Session 7
Wednesday 4th September 2019
13:05 - 13:10 (ePoster Station 3)
Exhibition Hall
Constipation Imaging Gerontology Neuropathies: Central Neuropathies: Peripheral
1.Neurology, Internal Medicine, Sakura Medical Center, Toho University, 2.Neurology, Chiba University, 3.International University of Health and Welfare, 4.Continence Center, Dokkyo Medical College, 5.Uro-Neurology, National Hospital for Neurology & Neurosurgery, London
Presenter
R

Ryuji Sakakibara

Links

Poster

Abstract

Hypothesis / aims of study
We describe a newer concept “Lewy body constipation”, i.e., constipation due to Lewy body diseases (LBD) (Parkinson’s disease, dementia with Lewy bodies), with minimal non-gastrointestinal symptoms, such as REM sleep behavior disorder, overactive bladder, mild cognitive impairment, and minimal or no gait difficulty.
Study design, materials and methods
This study was a prospective cohort study: recruiting period, 5.0 years; prospective follow-up period, 5.5±3.0 years, visit at least once a year. We recruited 745 referred subjects.  The inclusion criteria were: at least one of the known nonmotor features of PD, i.e., autonomic (e.g., postural hypotension with systolic pressure fall > 20 mmHg, usually with a more widespread autonomic failure but without any motor or cognitive disorder [pure autonomic failure, PAF], constipation, bladder dysfunction), sleep (e.g., REM sleep behavior disorder (RBD)), cognitive (including mild cognitive impairment [MCI] or psychiatric [apathy, depression, anxiety, hallucination] symptoms). All these items are being recently regarded the markers for the early PD 4; and having undergone both a DAT scan (the threshold of specific binding ratio at our hospital is 3.0) and an MIBG test (the threshold of heart vs. mediastinum ratio in the delayed images at our hospital is 2.0) (Fig. 1).  All patients and their families gave informed consent before participating in the study.
Results
During the recruiting period, after the initial workup, only 18 patients fulfilled the above criteria. Most of them were referred from local general physicians for an assessment of neurologic etiologies of syncope, constipation, overactive bladder, RBD, and memory disorder. The patients were uniformly elderly (mean age 75.5 years; range 67–86 years), had long histories (age of onset 61.0 years, range 53–79 years; duration of disease 14.5 years, range 1–37 years), had male dominance (14 men and four women). All patients could walk independently. The neurologic diagnoses of the patients were constipation/RBD in 10 (56%), constipation/ RBD/ PAF in six (33%), and constipation/PAF in the remaining two patients (11%), based on their clinical and laboratory manifestations.
During the prospective follow-up period, in the most recent one year, seven of the patients (39%) developed a motor/cognitive disorder that might need medication: motor (PD) (n=5, 3 changed from constipation/RBD, 2 from constipation/RBD/ PAF), cognitive (mild cognitive impairment [MCI]) (n=1, from constipation/RBD), and both motor and cognitive (dementia with Lewy bodies) (n=1, from constipation/RBD/PAF). Motor disorder in these 5 patients was mild and akinesia/gait freezing dominant. Three of them were started on levodopa, and the effect was moderate in all patients. 
Among the 18 patients, all but one (n=17, 94%) had an abnormal MIBG test result, whereas only 56% (n=10) had an abnormal DAT scan (Fig 2).
Interpretation of results
The underlying mechanisms seem to be as follows. 1) Epidemiological studies in a Japanese-immigrant cohort in Hawaii, USA indicated a clear association between constipation and the future risk of developing motor signs (namely, PD) in LBD. The interval between the questionnaire of constipation to the development of motor sign was more than 10–20 years in those studies. 2) Serial pathology by Braak and colleagues showed that PD pathology in the brain starts in the dorsal vagal nucleus (that might regulate bowel function) earlier than in the substantia nigra (that regulates motor function). Gelpi et al. further reported that alpha-synuclein aggregates (pathological hallmark of PD) tended to appear in the peripheral nerves earlier than in the brain: e.g., vagus nerve (86.7%), myenteric plexus (86.7%), cardiac sympathetic nerve (100%), etc. 3) Environmental toxins (particularly pesticides in rural regions) may change microbiota (bacterial flora) in the bowel, triggering myenteric LBD pathology, and developing constipation by epidemiological and experimental studies. 4) Once LBD pathology starts in the myenteric plexus, it is postulated that aggregated α-synuclein (a marker of LBD pathology) has the ability to transmit (like prion) from neuron to neuron, then spread to the brain through sympathetic (thoracic and lumbar sympathetic trunk) and parasympathetic (vagal and pelvic) nerves (ref. 1,2). 
Our study result may indicate myenteric LBD pathology in the very early stage in situ by the aid of two neuroimaging.
Concluding message
Our results indicate that “Lewy body constipation” might consist of an important  part of elderly constipation. This is because DLB is not uncommon, occurring in up to one in fifteen of general octogenarians. “Lewy body constipation” needs particular care since it may lead to gastrointestinal emergencies such as intestinal pseudo-obstruction, introsusception, volvulus, stercoral ulcer, etc.
Figure 1 Fig 1 Two neuroimaging tests for Lewy Body Constipation.
Figure 2 Fig 2 Positive rate of two neuroimaging tests for Lewy Body Constipation.
References
  1. Tateno F, Sakakibara R, Kishi M, et al. Constipation and metaiodobenzylguanidine myocardial scintigraphy abnormality. J Am Geriatr Soc. 2012; 60: 185-187.
  2. Gelpi E, Navarro-Otano J, Tolosa E, et al. Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders. Mov Disord. 2014; 29: 1010-18.
Disclosures
Funding None Clinical Trial No Subjects Human Ethics Committee Ethics Committee, Sakura Medical Center, Toho University Helsinki Yes Informed Consent Yes