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Advanced Neurology Neurophysiology in hypokinetic disorders

TMS study suggested that the quantification of cerebellar especially in the absence of reliable markers. Moreover, the
inhibition (CBI) could be a neurophysiological marker of discrimination of early PD and APS is challenged by the
MSA progression, particularly the MSA-C phenotype. relatively similar clinical symptoms.
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CBI directly regulates motor cortex activity and can be The use of semi-quantitative EEG was assessed for
measured from the decrease of MEPs following a single- its ability to distinguish PD from APS and among APS
pulse TMS stimulation. In this context, healthy individuals conditions. This approach involved a grand total EEG
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would have higher CBI as compared to MSA-C patients, and (GTE) score, assessing the posterior background and slow
low CBI (i.e., in MSA-C patients) is commonly associated wave activities. It was reported that PD patients exhibited
with ataxia. This finding suggested that CBI could be used the lowest GTE score, followed consecutively by CBS, MSA,
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as a prognostic marker of MSA-C progression.
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and PSP patients (in increasing GTE scores). A GTE
3.3.2. Neurophysiological features of PSP score of ≤9 could distinguish PD from APS patients with
a sensitivity of 100% and a specificity of 33.3%. Despite
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Recent neurophysiological studies on PSP were conducted these results, GTE was not able to precisely distinguish
with the use of TMS to define the pathophysiological role APS conditions. 36
of M1 in PSP. 33,34 In a study, PSP Richardson syndrome
patients and healthy controls underwent SICI, SICF, R2BRRC is a neurophysiological tool used to measure
intracortical facilitation (ICF), and QPS over M1 (i.e., with brainstem excitability, which is usually altered in several
an interstimulus interval (ISI) of 5 ms to induce an LTP- movement disorders. Only a few studies on BR and R2BRRC
like effect), and it was reported that the LTP-like effect was in APS were reported in recent years. 40-43 In particular,
reduced in the PSP group and negatively correlated with R2BRRC could differentiate patients with tauopathies,
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UPDRS-III score, especially bradykinesia. Notably, none of that is, PSP and CBS. The use of a recovery cycle
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the other cortical excitability parameters differed from those demonstrated that patients with PSP exhibited increased
of controls or correlated with any clinical features. Therefore, brainstem excitability, with high specificity and sensitivity
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40
the degree of LTP alterations in PSP could reflect the severity in distinguishing PSP from CBS. Recently, R2BRRC was
of bradykinesia and M1 cortical impairment. However, used to discriminate APS with similar clinical phenotypes,
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TMS may not be useful in clinical practice, especially for as well as APS from early PD. 37,38 The identification of
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differentiating drug-naïve PSP and PD at the early stage. accurate R2BRRC cutoff scores to distinguish each APS
Amplitude and latency of MEPs, central motor conduction has suggested that R2BRRC could be a reliable tool in the
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time (CMCT), RMT, and cortical silent period (CSP) were differential diagnosis of APS in daily clinical practice.
recorded in drug-naïve PSP and PD patients and healthy At an ISI of 100 ms, a cutoff value greater than 33% could
controls, and it was subsequently reported that higher MEP differentiate CBS from PSP with a sensitivity of 91.3% and a
amplitude and longer CSP were observed in PD and PSP specificity of 92.9%. In contrast, a cutoff value of 23% could
patients than in the healthy controls. Therefore, PD and distinguish CBS from MSA with a sensitivity of 93.3% and
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PSP may share relatively similar neurophysiological features a specificity of 92.9%. Therefore, it was hypothesized that
in the early stages (based on TMS). The overlapping clinical the normal brainstem excitability observed in CBS patients
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and neurophysiological features between PD and PSP further could be related to the absence of a brainstem involvement,
highlight the challenge of an accurate differential diagnosis and this brainstem excitability is from PSP and MSA,
of similar hypokinetic disorders and the significance of regardless of the underlying pathology. 37
developing novel and effective electrophysiological tools to Similarly, the differential diagnosis between drug-
distinguish these disorders. naïve PD, MSA, and PSP patients with predominant
3.3.3. Neurophysiological features of CBS Parkinsonism is challenged by the relatively similar clinical
features at the early onset of the diseases. A recent study
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In 2019, Stasio et al. summarized the neurophysiological investigated the possible asymmetric brainstem excitability
findings (reported before 2019) related to CBS of untreated PD, MSA, and PSP patients and evaluated the
pathophysiology in a review article. Herein, the differences through a side-to-side comparison associated
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neurophysiological features of CBS, with emphasis on with the computation of an asymmetry index (AI) of
differentiating APS, are summarized in Table 2. 36-39 R2BRRC. The AI of R2BRRC was calculated with the
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3.3.4. Neurophysiological assessments for the formula:
differential diagnosis of APSs ([Side 1 – Side 2]/[Side 1 + Side 2])
The differential diagnosis among MSA, PSP, and CBS Where Side 1 and Side 2 (referring to MAS and LAS,
patients is often difficult at the early onset of the disease, respectively) are the percentage values of R2BRRC at each

Volume 3 Issue 1 (2024) 7 https://doi.org/10.36922/an.1961