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Staging System Classifies Nearly All Patients With Lewy Body Synucleinopathy

The Unified Staging System for Lewy Body Disorders can categorize patients, regardless of their specific synucleinopathies.


 

LOS ANGELES—The Unified Staging System for Lewy Body Disorders (USSLB) enables the categorization of almost all brains with Lewy body synucleinopathy, according to research described at the 70th Annual Meeting of the American Academy of Neurology. The USSLB’s stages correlate significantly with motor and nonmotor findings. “Wider use of the USSLB would help standardize research in synucleinopathies,” said Charles H. Adler, MD, PhD, Professor of Neurology at Mayo Clinic in Scottsdale.

Charles H. Adler, MD, PhD

Investigators have developed several neuropathologic staging systems for Lewy body disorders, but many focus on specific diseases, such as Parkinson’s disease or dementia with Lewy bodies. They thus do not allow the classification of all patients with Lewy body disorders. In addition, the literature contains few data about how well these systems’ stages correlate with clinical and pathologic findings.

The Emergence of the USSLB

Dr. Adler and colleagues proposed the USSLB in research published in Acta Neuropathologica in 2009. Their goal was to enable the classification of patients with Lewy body disorders, regardless of their specific diagnoses. The USSLB includes four stages. Stage I denotes pathology limited to the olfactory bulb. Stage IIa denotes predominantly brainstem involvement. Stage IIb refers to pathology predominantly in the limbic system, rather than the brainstem. Stage III denotes pathology in the brainstem and limbic system. Stage IV represents neocortical pathology.

To examine the correlation between patients’ motor and nonmotor findings, including cognitive measures, and the extent of Lewy-type synucleinopathy, as categorized by the USSLB, Dr. Adler and others examined data from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). That study includes participants in the Banner Sun Health Research Institute brain and body donation program. Participants undergo annual clinical exams that include movement testing, cognitive testing, sleep and autonomic questionnaires, and a smell test.

The investigators searched the AZSAND database for patients who presented from January 1997 through December 2015. They identified 641 autopsies. Clinical data and information on Lewy-type synucleinopathy were available for 280 of the cases. The population included cases with Lewy bodies and those with synuclein pathology within the neuropil and fibers. The population’s mean age at death was 83. Greater severity of synucleinopathy was associated with younger age at death.

Braak Staging Could Not Characterize Some Patients

The researchers classified 8.6% of cases as Stage I, 15.4% as Stage IIa, 13.6% as Stage IIb, 31.8% as Stage III, and 30.7% as Stage IV. Cognition was normal in 25.7% of the cases, 8.6% had mild cognitive impairment, and 65.7% had dementia.

“We had a lot of patients with dementia who had early-stage Lewy synucleinopathy,” said Dr. Adler. “The reason for that is that we had a tremendous number of Alzheimer’s disease brains, which have olfactory-bulb-only or early-stage Lewy synucleinopathy.”

Multiple measures of motor parkinsonism and cognitive impairment, as well as of hyposmia and probable REM sleep behavior disorder, correlated significantly with increasing USSLB stage. A few clinical features had no correlation with USSLB stage.

Dr. Adler and colleagues also applied the Braak staging criteria to the cases. To classify all cases, the investigators added an olfactory-bulb-only stage to the Braak criteria. Of the initial cohort, 70 cases could not be assigned a Braak stage. When the researchers removed cases with Alzheimer’s disease, 21% of cases could not be staged.

“The USSLB is an improvement on previously published Lewy body staging systems,” said Dr. Adler. The system provides clear rules for classification and assesses 10 brain regions.

—Erik Greb

Suggested Reading

Beach TG, Adler CH, Lue L, et al. Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol. 2009;117(6):613-634.

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