**1. Introduction**

298 Neuroimaging for Clinicians – Combining Research and Practice

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Parkinson Disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) are characterized by deposition of Lewy Bodies (LB), consisting of eosinophilic intracellular (intraneural in PD and DLB and intraglial in MSA) inclusions of α-synuclein and allowing the three disorders to be categorized as synucleinopathies. The identification in the last two decades of specific clinical features of synucleinopathies has been a major breakthrough in Neurology, as it prompted a reconsideration of diagnostic and therapeutic approaches to dementia and parkinsonism. The recognition of synuclein and ubiquitin markers in dementia resulted in the reclassification of patients previously considered as affected by Alzheimer Disease (AD) and Vascular Dementia (VaD), and there is now agreement that DLB is the second most common cause of dementia in elderly population: its prevalence is reported to be in the 25-43% range in different studies.

DLB is clinically characterized by the presence of prominently dysexecutive dementia (frontal lobe or subcortical dementia according to earlier classification [1]), cognitive fluctuations, consisting of remitting-relapsing episodes of blunted conscience reaching levels of stupor, by the occurrence of visual hallucinations and delusions, by parkinsonian motor signs and hypersensitivity to neuroleptic treatment, ranging from worsening of parkinsonism to the possible lethal neuroleptic-malignant syndromes [2]. Yet, variances of presentation and overlapping symptoms with AD and Fronto-Temporal lobe Degeneration (FTD), could be misleading in the process of addressing a clinical diagnosis with consequent therapeutic risks(e.g. introducing neuroleptic treatments in patient with DLB), or economic costs (e.g. addressing patients with DLB to treatment protocols dedicated to AD patients, based on vaccines or antibodies against β amyloid proteins, a neuropathological feature of AD).

It is evident the stringent need for improvement of reliable diagnostic tools (u.e. biomarkers) to differentiate the diseases associated with dementia. In 2010 the National Institute of Health, NIH, held a symposium focused on the development of possible biomarkers for DLB. Among the different suggested biomarkers, neurophysiological assessments were reconsidered, as a large amount of neurophysiological studies had been devoted to AD and PD, whose characteristics are shared by DLB.

Is There a Place for Clinical Neurophysiology Assessments in Synucleinopathies? 301

PARKINSON'S DISEASE LB/DYSTROPHIC NEURITIS INTRACYTOPLASMIC LEWY BODY DEMENTIA LB/DYSTROPHIC NEURITIS INTRACYTOPLASMIC

LB/DYSTROPHIC NEURITIS

FAILURE LB INTRACYTOPLASMIC

PLAQUES (Aβ AMYLOID) TANGLES PHF/TAU LB/α-SYNUCLEIN

CYTOPLASMATIC GLIAL

LB/CYTOPLASMATIC GLIAL

UBIQUITIN, INCLUSION SOD 1,

The central clinical feature of DLB is progressive dementia prominently characterized, in the early phases of the disease, by deficits in attention, executive function and visuospatial ability, at difference with AD where memory impairment is the main early feature of dementia. Fluctuations in attention and alertness, recurrent complex visual hallucinations and parkinsonism represent the core features for the diagnosis. Suggestive clinical features are REM sleep behavior disorder, severe sensitivity to neuroleptics and low dopamine transporter uptake in the basal ganglia demonstrated by single photon emission computerized tomography (SPECT) or Positron Emission Tomography (PET) imaging. Supportive features are often present and are represented by repeated falls and syncopes, transient and unexplained loss of consciousness, severe autonomic dysfunction (e.g., orthostatic hypotension, urinary incontinence), hallucinations in other modalities than visual, systematized delusions, depression, relative preservation of medial temporal lobe structures on CT or MRI scans, generalized low uptake on SPECT/PET perfusion scans with low occipital activity, abnormally low uptake on 123I-metaiodobenzilguanidine (123I-MIBG)

In this last revision of criteria for the diagnosis of DLB, electroencephalography (EEG) abnormalities with transient slow waves or sharp waves were also reported as supportive

We performed a prospective study evaluating the incidence and characteristics of EEG abnormalities in patients affected by AD, DLB and PD with Dementia at their first

INCLUSION INTRACYTOPLASMIC

INCLUSION INTRACYTOPLASMIC

INTRACYTOPLASMIC

INTRACYTOPLASMIC EXTRACELLULAR INTRACELLULAR

EXTRACELLULAR/ INTRACYTOPLASMIC

INTRANUCLEAR, INTRACYTOPLASMIC

**SYNUCLEINOPHATIES LESION/COMPONENTS LOCATION** 

TANGLES PHF/TAU

Aβ-PLAQUES

DYSTROPHY AXONAL SPHEROIDS

Table 1. Sinucleinophaties and LB location.

LB

LEWY BODY VARIANT OF ALZHEIMER

PURE AUTONOMIC

MULTIPLE SYSTEM

HALLERVORDEN-SPATZ DISEASE

NEUROAXONAL

AMYOTROPHIC LATERAL SCLEROSIS

DOWN SYNDROME MOTOR NEURON

myocardial scintigraphy [2].

features for the diagnosis[2,4].

ALZHEIMER'S DISEASE

DISEASE

ATROPHY

OTHER:

DISEASE

We contributed to several studies on this argument along the years, and in the present chapter we discuss the role of clinical neurophysiological studies in DLB in comparison with other disorders. The essential background of our original studies laid in the fact that most historical studies were performed when the DLB clinical entity was unknown and therefore some of the past results were marred by absent recognition of this clinical entity.
