ReviewNeurophysiological correlate of clinical signs in Parkinson's disease
Introduction
Electrophysiological examination is still scarcely used in the assessment of central nervous system (CNS) diseases. However, many tests available to most neurophysiological laboratories in present days can be used to document and quantify symptoms and signs found in patients with CNS diseases, and provide information on the underlying pathophysiological processes. Disturbances in motor control can be assessed through the analysis of electromyographic (EMG) activity and movement during performance of voluntary or involuntary actions. Abnormal reflex reactions can be an expression of disturbed neuronal excitability, and may be assessed by measuring the size and latency of reflex responses. The examination of central conduction time for sensory and motor pathways with evoked potentials (EPs) and transcranial magnetic stimulation (TMS) provides useful information on excitability of certain areas of the CNS.
Parkinson's disease (PD) is a degenerative disorder that presents with a constellation of symptoms and signs known as parkinsonism. However, parkinsonism is not the only feature of patients with PD, or specific for PD. An accurate history and a thorough physical examination are still of paramount importance in correctly classifying patients with parkinsonism (Jankovic et al., 2000, Marjama-Lyons and Koller, 2001). According to current diagnostic criteria (Koller, 1992, Calne et al., 1992, Hughes et al., 1992), patients can be considered to have PD when they have bradykinesia and at least one of the following: rigidity, tremor, or postural instability with no known other causes, and do not have any of the signs considered atypical for PD (Table 1). However, because no diagnostic biologic marker is available, the diagnosis of PD requires frequent clinical reassessment (Jankovic et al., 2000, Viallet, 2000). Additional diagnostic requirements used by some authors in protocolized studies are evidence of a progressive disorder, and asymmetric onset of symptoms or signs (Ward and Gibb, 1990). Apart from parkinsonism, other features of patients with PD include cognitive disorders (Levin et al., 1992, Starkstein et al., 1992), depression (Melamed, 1997), olfactory dysfunction (Stern et al., 1994), seborrheic dermatitis (O'Neill et al., 1994), sleep disorders (Kales et al., 1971), autonomic dysfunction (Goetz et al., 1986), etc. Other degenerative diseases of the CNS presenting with parkinsonism, that should be differentiated from idiopathic PD, are progressive supranuclear palsy (PSP), multisystem atrophy (MSA), cortico-basal ganglionic degeneration (CBGD), and secondary causes of parkinsonism. The similarities between these disorders regarding their clinical presentation are probably the reason why about 25% of the patients clinically diagnosed to have idiopathic PD have actually other pathological diagnoses (Hughes et al., 1992). Neurophysiological examinations can be of some help to the clinician in reaching a more accurate differentiation between parkinsonisms, on the basis of the characterization of their specific symptoms and signs (for a review, see Valls-Solé, 2000).
The rationale for performing neurophysiological studies in patients with PD may be twofold: on the one hand, electrophysiological examination should provide documentation and quantitation of symptoms and signs while on the other hand, electrophysiological abnormalities, even those with no clear clinical correlate, can furnish information on pathophysiological mechanisms underlying some clinical manifestations and therefore, be the basis for a better understanding of disease mechanisms. Well-documented electrophysiological data should be relevant for diagnostic and differential diagnosis purposes. Some of the most relevant electrophysiological findings reported in patients with PD are listed in Table 2.
Section snippets
Neurophysiological evidence of basal ganglia dysfunction
From anatomical and electrophysiological studies in animals, several authors have agreed on a theoretical model of basal ganglia motor circuitry, the dysfunction of which would explain the pathophysiology of some symptoms in PD (Alexander and Crutcher, 1990). This theoretical model implies both direct and indirect striato-pallidal connections, whose activity is regulated by the nigro-striatal dopaminergic system. Degeneration of nigral cells should trigger adaptive hyperactivity changes in
Akinesia/bradykinesia
The term bradykinesia is used to describe slowness of movement, while the term akinesia refers to the delay in onset of a voluntary movement (Hallett and Khoshbin, 1980, Hallett, 1990, Pascual-Leone et al., 1994a). Therefore, the measurement of movement onset or of the onset of EMG activity in reaction time paradigms are useful tools for assessing the degree of akinesia/bradykinesia. Simple and complex reaction time task paradigms have been the subject of many studies with PD patients (Table 3
Abnormalities in brainstem reflexes and functions
In many extrapyramidal disorders, facial reflexes with short latency times (like the jaw-jerk, the R1 of the blink reflex, and the first phase of the masseteric inhibitory reflex) are unaltered. This observation indicates that the afferent and efferent fibers of the reflex arc and the brain stem mono- or oligosynaptic circuits are not directly affected by these diseases. In contrast, reflexes with longer latency times and polysynaptic pathways, which undergo a strong suprasegmental influence,
Sensitivity and specificity of neurophysiological signs in PD
Sensitivity of clinical neurophysiological tests is, in general terms, not powerful enough for determining the positive diagnosis of IPD. Some of the neurophysiological observations reported above have also been obtained in patients with degenerative diseases other than IPD, suggesting at first glance that neurophysiological tests are also not specific for PD. The results of neurophysiological tests reflect in a rather indirect way the clinical state of the patient more than etiological
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