In the year of 1817, James Parkinson (1775–1824), a physician and geologist who lived
near London, England, published his monograph “An Essay on the Shaking Palsy”[1]. Within his work, he described greatly what had been seen a long time before him
by individuals like Galen[2],[3], known at that time as paralysis agitans. Approximately fifty years after his publication, Jean-Martin Charcot (1825–1893)
and his students at the Salpêtrière Hospital in Paris, France, complemented the analyses
of the disease by naming it as we know today, Parkinson's disease (PD), and distinguishing
it from other similar diseases at that time, as multiple sclerosis[2],[4]. Furthermore, Charcot and his students identified atypical variants of what was
defined as the classic PD. Those variants were called PD without tremor, PD with hemiplegia,
and PD with extended posture[2],[5]. Nowadays, these variants are known to be atypical parkinsonism, as progressive
supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal degeneration
(CBD)[2].
Among different predominant features of PD seen at that time, as bradykinesia and
rigidity, one of Charcot's students, Arthur Dutil, described, in 1889, a woman with
parkinsonian features and abnormal eye movements. Although no clear description of
supranuclear palsy was reported, the presence of retrocollis and erect trunk suggest
a PSP phenotype[6]. Prior to Dutil, in 1838, an interesting report was made by Marshall Hall, when
he wrote “a peculiar lateral rocking motion of the eyes” regarding a 28-year-old male
thought to be a case of PD[7].
Throughout the first half of the 20th century, authors, including E. Krebs, in 1925, and A. Bielschowsky, in 1935, have
described abnormal eye movements in patients with PD[8]. Fisher, in 1924, and Portman, in 1932, found first degree spontaneous nystagmus
that appears when the patient gazes in the direction of the fast component to be frequent
in PD[9],[10]. After the influenza epidemic of 1916–1917, there was an important increase in cases
of postencephalitic parkinsonism[2]. Therefore, many studies were based on the observation of postencephalitic parkinsonism
cases[11], which occur with characteristic oculogyric crisis, pupillary changes, and gaze
palsies[12]. Alexandre, in 1939, and Fracasso and Palatini, in 1941, however, found first degree
spontaneous nystagmus to be rare in patients with PD.
Research on abnormal eye movements in parkinsonian disorders was intensified in the
second half of the 20th century ([Figure 1]). In 1972, Corin et al.[8] published an important case-control study on oculomotor dysfunction in PD[8] and described some dysfunctions as the saccadic, pursuit, and vergence in approximately
75% of patients. As the criteria for PD was not mentioned in these ancient studies,
we can assume that at least part of their sample had parkinsonian syndrome other than
PD as we define today.
Figure 1 Parkinson's disease and Parkinsonisms’ timeline.
By the year of 2020, much has been known about the association of parkinsonism and
abnormal eye movements, their role in differential diagnosis of parkinsonian disorders,
and their potential aid to better elucidate diseases pathophysiology.
Among parkinsonism and movement disorders, PD appears to have less prominent oculomotor
abnormality[13] ([Table 1]). Nevertheless, hypometric voluntary saccades, saccadic intrusions during eye fixation,
impaired vertical soft search/tracking movements and convergence insufficiency can
be seen in PD and worsen as disease progresses[13],[14]. In comparison, PSP patients present oculomotor disorders in early disease stage,
including frequently slow vertical saccades with normal speed horizontal saccades
(although often hypometric) that also become slow with disease progression, and impaired
convergent ocular movements and linear vestibulo-ocular reflex. PSP is liable to be
confused with CBD in consequence of the vertical paralysis of supranuclear gaze[13],[14]. However, it was observed that CBD presents with significant increased latency of
horizontal saccades, while PSP presents with a decrease of saccade speed[13],[14].
Table 1
Ocular motor abnormalities in parkinsonism, adapted from Jung[13].
|
Diagnosis
|
Parkinson's disease
|
Progressive supranuclear palsy syndrome
|
Corticobasal syndrome
|
Multiple systemic atrophy
|
|
Saccadic intrusions
|
+
|
++
|
+
|
+
|
|
Vertical saccades
|
Hypometric
|
Slowed, early
|
Impaired, late
|
Hypometric
|
|
Horizontal saccades
|
Hypometric
|
Slowed, late
|
Delayed
|
Hypometric
|
|
Blepharospasm or eyelid apraxia
|
Very rare
|
Common
|
Common
|
Rare
|
|
Smooth pursuit
|
Mild
|
Severe
|
Mild
|
Moderate
|
In 2016, Yu et al.[15]drew attention to reading disturbance in PD analyzing a 40-year-old man with a six-year
history of disease. The man was on dopamine-replacement therapy, had high schooling
levels and good eye movement control. His ability in making alternating fixations
and saccades during number reading was normal on the neuro-ophthalmic examination.
Nevertheless, his word reading was significantly slowed and abnormal due to increased
number of saccades, smaller saccade amplitudes, increased number of regressive saccades
and longer fixation durations.
Waldthaler et al.[16], in 2018, also characterized eye movements during reading in PD patients. They suggest
that eye movements during reading reflect cognitive impairment in PD. Wong et al.[17] had explored the relationship between the eye movement parameters and performance
in cognitive tests in multiple domains. As a result, it was found that the prolonged
duration of fixation was associated with poorer performance in verbal fluency, visual
and verbal memory. Gorges et al.[18] analyzed eye movements using video-oculography and correlated the findings with
functional brain mapping obtained from task-based/no-task-based functional magnetic
resonance imaging (MRI). The results show that the worst oculomotor performance is
associated with the severity of the functional impairment of the brain structures
involved with the disease. These findings may allow further exploration of the use
of eye movement parameters as a clinical proxy for cognitive function markers in patients
with PD. Similarly, Barbosa et al. described an association between the saccadic direction
error with impulse-compulsive behavior in PD patients[19].
Another interesting line of study is the analysis of the different inherited parkinsonian
syndromes and their dysfunction profiles in the basal ganglia. The study, carried
out in 2017 by Pretegiani et al.[20], compared the pattern of alteration of attributes of horizontal saccades, vertical
saccades and antisaccades in PD and different forms of genetic parkinsonism, such
as PARK1, PARK2, PARK6 and PARK9 inherited forms of PD, in addition to neurodegeneration
with brain iron accumulation (NBI) and Gaucher Disease, among others. The results
show that each one of the mentioned diseases may have a different pattern of changes
in the saccadic movements. Such a study allows important inferences to be made about
the different dysfunctions presented by the basal ganglia in these syndromes.
In conclusion, the differential diagnosis of PD is relevant for prognosis, treatment,
and research, and, despite major advances in the field, it still remains largely clinical.
The relevance of eye movement examination has grown alongside the history of PD and
has proven to be an excellent tool for differential diagnosis of parkinsonism[13],[21]. Moreover, it may become an aid to identify different forms of genetic PD, and useful
to improve early recognition of cognitive decline in PD patients.
