also responses in the orbicularis oculi muscle. The exception were the patients with PSP, who had no orbicularis oculi responses even if the responses of the mentalis muscle were not different from those observed in the other groups of patients (Fig. 3B). This abnormality probably reflects the activation of two different circuits by the median nerve afferent volley. The mentalis response could be conveyed through the cortico-nuclear tract, since this tract innervates predominantly lower facial moto-neurons (53), and a transcortical loop has been suggested because of the contiguity between thumb and chin areas in the brain sensorimotor region (52,54). The selective damage of the pontine reticular formation in patients with PSP would be responsible for the absence of the orbicularis oculi response. Enhancement of mentalis response may occur because of disinhibition of thalamo-cortical connections from their striatal control (54).
One of the earliest contributions of electromyography to the assessment of central nervous system (CNS) abnormalities in patients with parkinsonism was made by Kimura in 1973 (55). Kimura demonstrated in these patients the existence of an abnormal decrease of habituation of the blink reflex to paired supraorbital nerve electrical stimuli. The fact that the abnormalities occurred in the R2 but not in the R1 component of the blink reflex suggested that the disturbance lies in the interneurons rather than in the motoneurons. Since then, many authors have studied the blink reflex excitability recovery curve to paired stimuli, by dividing the size of the response to the test stimulus by that of the response to the conditioning stimulus. This sign has been reported not only in parkinsonism, but in many other disorders as well (56,57). It is therefore of little use for differential diagnosis between degenerative disorders. In clinical practice, the assessment of enhanced trigemino-facial reflex excitability may be of interest for documenting the existence of an abnormal function of brainstem interneurons in patients in whom clinical assessment is dubious or at early stages of their disease. We found similar interneuronal brainstem excitability enhancement in IPD, PSP, and MSA patients (47). Figure 4 shows the proposed circuit of basal ganglia control of trigemino-facial reflex excitability, according to Basso and Evinger (58) and Basso et al. (59), and the dysfunction likely occurring in parkinsonism.
Neurophysiological abnormalities have been reported in other brainstem reflexes in parkinsonism, although they have not been investigated specifically in APDs (60-62). It has been shown that the second inhibitory period of the masseteric exteroceptive inhibitory reflex has an enhanced excitability recovery cycle, similar to that of the blink reflex in patients with IPD. The same excitability recovery abnormalities have been reported in parkinsonism and dystonia (60).
The Startle Reaction and the Startle-Induced Modulation of Reaction Time
The startle reaction in experimentation animals is known to be generated in the nucleus reticularis pontis caudalis (nRPC), which activates the reticulospinal tract inducing muscle responses in facial and spinal motoneurons (63). In humans, the startle reaction is also thought to originate in corresponding nuclei of the brainstem, and spread caudally and rostrally to limb and facial muscles.
Abnormalities in the startle reaction can be related to enhancement or reduction of the response size. One example of abnormal startle response enhancement is hyperkeplexia (64), whereas an abnormal startle response reduction takes place in patients with PSP (48). The decrease of the startle reaction in PSP patients should not be surprising, since neuronal loss in these patients involves specifically the cholinergic neurons of the lower pontine reticular formation, where the startle reaction is generated. Neuronal loss has been reported in the pedunculo-pontine tegmental nucleus and the nucleus reticularis pontis caudalis (65-67). In the study carried out by Vidailhet et al. (48), the response was absent in three out of eight patients, and it was small and delayed in the other five patients. The same finding was later replicated by Valldeoriola et al. (22), who carried out a comparative study of PSP and other APDs.
Whereas response enhancement is easy to identify because of reactions of larger size and decreased habituation, assessment of an abnormal reduction of the response may be more difficult because of the fact that the response habituates easily in healthy subjects (49). For this reason, the observations made in experiments in which the startling stimulus was applied together with the imperative signal in the context of a reaction time task paradigm should be helpful for clinical purposes. Using such methods, Valls-Sole and coworkers (68-70) made a few interesting observations in healthy subjects:
1. The startling stimulus applied together with the imperative signal of a reaction time task induces a significant acceleration in the execution of the intended movement. The ballistic movement is executed without any distortion but at a significantly faster speed (70).
Clinical application of the collision between a startle reaction and the voluntary activity in a reaction time task paradigm (the StartReact effect) was reported by Valldeoriola et al. (22). These authors found that patients with PSP not only had absent startle reaction but they were also not able to accelerate their voluntary reaction when the startling stimulus was applied together with the imperative signal.
In contrast to patients with PSP, patients with MSA have normal auditory startle reaction in facial and cervical muscles (71). Furthermore, when the responses of cranial and limb muscles are analyzed together, MSA patients had enhanced probability of a response, shortened onset latency, and enlarged response magnitude compared to normal controls (72,73). In the only analysis of the startle response in patients with LBD, Kofler et al. (73) reported fewer and abnormally delayed ASR of low amplitude and short duration in extremity muscles in comparison to healthy controls. Two more details of the studies of Kofler and coworkers (72,73) are relevant for the discussion of the contribution of the startle reaction to the differential diagnosis of APD patients. One is the fact that three patients with MSA had no response to the startle reaction, indicating that absence of the startle reaction is not a feature exclusive to PSP patients (48). A particularly high density of oligodendroglial cytoplasmatic inclu sions in the brainstem area responsible for the generation of the reticulospinal tract was assumed to be the cause of absent startle response in those MSA patients. Another observation made by Kofler et al. (72) was the existence of subtle differences in the characteristics of the response between MSA-P and MSA-C patients. Whereas MSA-P patients had a higher startle probability and a larger area and shorter latency of the motor response, patients with MSA-C had less habituation. Differences between the two groups in the inhibitory effect of the cerebellum over the motor cortex may be responsible for such neurophysiological observation (72).
A weak stimulus preceding by about 100 ms the startling stimulus has an effect of inhibition upon the startle reaction (prepulse inhibition). The prepulse stimulus may be of the same or a different sensory modality as the stimulus inducing the startle (50). In the blink reflex, an auditory prepulse causes enhancement of the R1 and depression of the R2 to electrical supraorbital nerve stimuli (74). In a study of prepulse inhibition in patients with IPD, Nakashima et al. (75) found that auditory prepulse stimuli induced an abnormally reduced inhibition of the R2 response of the blink reflex, and Lozza et al. (76) reported an abnormally reduced blink reflex inhibition after index finger stimulation. However, some patients with IPD have an abnormal auditory prepulse inhibition and a normal somatosensory prepulse inhibition (77). The different behavior of auditory and somatosensory prepulse stimuli in IPD patients could be owing to differences in the prepulse effectiveness of the same vs different sensory modality, differences in the arrival time of prepulse inputs to the brainstem centers, or to selective impairment of reticular formation neurons activated by auditory inputs. Patients with PSP have also absent or significantly reduced prepulse inhibition to both auditory and somatosen-sory prepulses (Fig. 5), revealing an even more striking dysfunction of the prepulse circuit in PSP compared to IPD. No data are available so far regarding prepulse inhibition in MSA patients.
A variety of tests determining the excitability of propriospinal interneurons (78,79) have been applied to patients with IPD, demonstrating reduced reciprocal (33,34) and autogenetic (Ib) inhibition (35), possibly related to the clinical expression of rigidity. These exams have not been done in patients with APDs, except for a single study of autogenetic inhibition (Ib inhibition) in patients with PSP (41). In such a study, the authors showed enhancement of the inhibition, the exact opposite of what was reported in patients with IPD. The explanation why opposite results have been found in these two groups of patients is, up to now, not clear.
Audiospinal facilitation is known as the effect of an auditory stimulus on spinal reflexes, specifically the soleus H reflex. The methods for audiospinal facilitation were developed by Rossignol and Jones (80) and Delwaide et al. (81). The stimulus to the posterior tibial nerve to induce the H reflex is applied between 0 and 110 ms after a loud acoustic stimulus. Healthy subjects have H reflex facilitation beginning at intervals between 60 and 80 ms, and lasting until the intervals of 100 or 110 ms. However, audiospinal facilitation is abnormally reduced in patients with IPD (12,81). Our own preliminary observations in patients with the clinical diagnosis of probable PSP is that they exhibit the same abnormality (82).
The recording of abnormal movements by means of surface EMG recording yields interesting information for the analysis of tremor, such as in patients with IPD (82). Tremor has also been reported in up to 74% of MSA patients (83). However, this figure included several types of tremor, with only a few patients exhibiting the resting tremor typical of IPD, and a large proportion of unclassifiable hands and finger "jerky" tremors, such as those shown in video segment 2. Electrophysiological studies of these latter movements have shown that their characteristics are closer to myoclonus than to tremor (84). A piezoelectric accelerometer was used to record finger movements and analyze the
Was this article helpful?