Keywords
cerebral microangiopathy - computerized dynamic posturography - idiopathic thrombocytopenia
- video head impulse test - videonystagmography - rotational chair - sinusoidal harmonic
acceleration - bilateral hypofunction
Cerebral microangiopathy (CM) is characterized by changes in small brain vessels including
small arteries, arterioles, capillaries, and small veins.[1] It is primarily diagnosed through neuroimaging studies such as magnetic resonance
imaging (MRI). Neurologic symptoms of CM include reports of seizures, vertigo, incontinence,
and other stroke or transient ischemic attacks. Gait apraxia has also been reported
in 27.8% of patients with CM.[2] Current treatment of CM is not clearly defined. While there is promising information
regarding reducing risk of developing CM, there is currently no agreed upon therapeutic
prevention or intervention strategy.[3] Current classes of drugs used to prevent or treat CM include, but are not limited
to, acetylcholinesterase inhibitors, anticoagulation medicines, anti-inflammatory
agents, antiplatelet agents, and blood pressure lowering medicines.[3]
The overall prevalence of immune thrombocytopenia (ITP), also known as idiopathic
thrombocytopenic purpura, is unknown, though a recent study estimates that it may
be close to 23.6 per 100,000 adults.[4] ITP is characterized by low platelet counts and is typically chronic in nature when
diagnosed in adults.[5] Chronic ITP is even less prevalent with estimates of 7.1 and 9.5 per 100,000 adults.[4] Patients with chronic ITP can develop antibodies that target other tissues or organs
in the body leading to the development of further illness and disease. Treatment strategies
for ITP are dependent on the severity of the presentation. Often those with milder
cases of ITP who have an acceptable platelet count are not actively treated rather
they undergo routine monitoring.[6] For those with lower platelet counts, corticosteroids are prescribed as a first
course of action. Due to ITP's characteristic low platelet counts, patients with ITP
are at risk for severe hemorrhage, due to decreased ability to clot. This increased
risk of severe hemorrhage is an important consideration when evaluating a person's
falls risk and general vestibular and balance function.
Case Study
Vestibular/Balance History
Our patient was a 64-year old male referred by his neurologist for vestibular evaluation
due to progressively worsening balance and feeling like he was “veering to the right”
while walking. The symptoms were first noticed 1 year prior to his date of evaluation,
and had significantly progressed in the past 6 months. The patient reported that he
felt the most unsteady when he walked in dark or dimly lit environments, particularly
on uneven surfaces like his lawn. The patient reported that he had previously been
seen by a physical therapist for vestibular rehabilitation, but had not perceived
any benefit from the therapy. He has fallen and has had near falls on several occasions
but had not yet sustained any serious injuries.
Audiological Evaluation
Comprehensive audiological testing performed at another facility 3 months prior revealed
symmetric mild to moderately severe sensorineural hearing loss bilaterally. He reportedly
had a significant history of work-related noise exposure. Speech recognition thresholds
were found to be in agreement with pure-tone averages. Word recognition testing revealed
a score of 88% at 65 dB HL in the right ear, and a score of 92% at 60 dB HL in the
left ear. Tympanometry revealed normal middle ear function with ear canal volume,
static compliance, and peak pressure to be within normal limits bilaterally.
Medical History
The following medical history was reported by the patient: arthritis, ITP, and high
blood pressure. Current medications were listed as Cialis and Metoprolol. The patient
denied any allergies, recreational drug use, tobacco use, or alcohol consumption.
He reported a 30-year history of knee injuries including at a total knee replacement
on the right side several years prior to the appointment. He reported that his initial
diagnosis of ITP was made several years prior and was based in part due to low platelet
levels. At the time of testing, he was under monitoring and not active treatment for
ITP as his platelet levels were above the recommended cutoff. At the time of testing,
he was under the care of his neurologist who had recently diagnosed him with CM based
off of abnormal imaging studies. He denied any significant cognitive decline.
Imaging Studies
Results of MRI performed with and without contrast revealed mildly prominent ventricles
and sulci, comparable to patient age. There was no reported evidence of mass or edema.
Mild white matter signal abnormalities were documented and attributed to the patient's
history of microangiopathy. No evidence of infarction or hemorrhage was reported.
Cerebellar tonsils were noted to be in normal location and intracranial vascular flow
voids were noted to be normal.
Methods
The following tests were performed at The Pennsylvania Ear Institute over the course
of two appointments: Halmagyi Head Thrust; computerized dynamic posturography (CDP)
battery including sensory organization test (SOT), motor control test (MCT), and adaptation
test (ADT) using Neurocom's Equitest system; videonystagmography (VNG) battery including
saccade, pursuit, optokinetic, gaze evoked/spontaneous nystagmus, Dix–Hallpike maneuvers,
static positional testing, and bilateral bithermal air calorics; rotational chair
studies including sinusoidal harmonic acceleration (SHA), step velocity (100 degrees/second
clockwise and counterclockwise), visual fixation (VFX) and visual enhanced (VVOR)
SHA testing via Micromedical VisualEyes system; and video head impulse test (vHIT)
via Micromedical's Vorteq vHIT system.
Results
Halmagyi Head Thrust
Our patient was unable to maintain stable VFX and multiple corrective overt saccades
were visualized during lateral head thrusts bidirectionally.
Computerized Dynamic Posturography
The CDP battery of tests was performed in the following order: SOT, MCT, and ADT.
SOT measures are obtained by measuring (via a force plate) the amount of postural
sway a person exhibits in a series of six different conditions. Each condition augments
the ability to use either vision, somatosensory, or vestibular senses in a systematic
manner. MCT evaluates motor control response of the lower extremities by quickly and
sporadically moving the force plate forward and backward. ADT measures the ability
to adapt to a sudden change including rotating toes up and rotating toes down.
SOT: Equilibrium index (EI) is calculated by measuring the amount of anterior and posterior
sway in each condition. EI scores are compared with age-matched normative data for
each condition as well as a composite EI. Normal EI scores were achieved during conditions
1, 2, and 3, with significantly reduced EIs and/or falls during conditions 4, 5, and
6, resulting in overall reduced composite EI ([Fig. 1]). MCT was completed next, and revealed that although the patient did fall into a
normal range for his composite score, he had abnormally long latencies in both large
forward and large backward translations ([Fig. 2]). These measures were analyzed and verified to be an accurate representation of
the patient's abilities. ADT was completed following MCT, and the patient was able
to successfully adapt to both the toes up and toes down stimuli.
Fig. 1 Sensory organization test comprehensive test results depicting abnormal composite
and individual equilibrium scores during conditions 4, 5, and 6. Sensory analysis
demonstrates ineffective use of vestibular and visual information resulting in a somatosensory-dependent
configuration. Strategy analysis depicts abnormal ankle-dominant movements. Center
of gravity alignment is normal.
Fig. 2 Motor control test results indicating normal weight distribution during testing.
Normal latencies were observed during all medium translations. Abnormally long latencies
were observed during large translations.
Videonystagmography
Ocular motor testing was performed using a 50-inch monitor and independent binocular
video recording goggles. The patient was alert and compliant throughout the evaluation.
No spontaneous or gaze-evoked nystagmus was observed with or without fixation. Smooth
pursuit testing was within normal limits for gain and symmetry; however, small saccadic
intrusions were visible on the eye tracing particularly at 0.4 Hz ([Fig. 3]). Saccade testing indicated abnormal accuracy (repeated hypometric responses), prolonged
latency, and reduced velocity measures ([Fig. 4]). Optokinetic testing was performed at a rate 30 degrees/second and revealed reduced
gain for left and right moving stimuli. Dix–Hallpike maneuvers were negative for torsional
nystagmus bilaterally. Static positional studies were conducted and a persistent six
degree per second right beating nystagmus was observed in head left without fixation,
which was suppressed with fixation. Seven degree left beating nystagmus present during
head right without fixation, which again was suppressed with fixation. During body
left, 11 degree per second right beating nystagmus was observed; and nine degree per
second left beating nystagmus was present during body right. In both body positions,
the nystagmus suppressed with fixation. The patient did not report any feelings of
motion during static positional testing. Bilateral bithermal caloric stimulation revealed
a significant bilateral weakness. The total slow phase velocity for all irrigations
was zero.
Fig. 3 Smooth pursuit tracing indicates normal gain and phase with subtle saccadic intrusions
at 0.4 Hz.
Fig. 4 Saccade results indicate abnormal velocity, consistent undershoots, and abnormally
long latencies.
Rotational Chair
SHA testing revealed low gain from 0.01 to 0.64 Hz. Due to low gain measures under
0.2 from 0.01 to 0.32 Hz, symmetry and phase were not calculated at those frequencies
([Fig. 5]).
Fig. 5 SHA results indicate severely reduced gain with no interpretable asymmetry or phase
measures. SHA, sinusoidal harmonic acceleration.
VFX with fixation light revealed normal gain, with no symmetry or phase calculated
as gain was below 0.2, as expected. VVOR with earth-stable optokinetic bars revealed
reduced gain with a measurement of 0.5 at 0.16 Hz, which is below normal limits and
consistent with previous test results.
Step velocity testing did not produce nystagmus, which resulted in abnormally low
gain and time constants in both the clockwise and counterclockwise directions.
Additionally, vHIT performed using the Micromedical System 2000 with vHIT attachment
in the lateral plane revealed reduced gain bidirectionally with possible covert saccades
([Fig. 6]). It should be noted that gain was calculated using area-under-the-curve method.
The measures of 0.7 fell below clinic normative data and 0.8 were considered borderline.
The bulk and weight of the device may have impacted test results.
Fig. 6 Lateral vHIT measures indicate abnormal gain, area under the curve with possible
covert saccades bidirectionally. vHIT, video head impulse test.
Discussion
Collectively, vestibular and balance results indicate severe bilateral horizontal
canal paresis with somatosensory dependence. The failure of the angular VOR is most
likely contributing to the patient's symptoms of blurred vision and instability while
walking in dimly lit and on uneven surfaces. Also unknown is the status of the vertically
aligned semicircular canals as vHIT was only performed in the lateral plane. It is
important to note that neither cervical nor ocular vestibular evoked myogenic potentials
were completed. Therefore, the function of the otolith organs and inferior vestibular
nerve cannot be accurately ascertained. However, his general gait instability and
poor performance on the SOT may indicate deficits in these areas as well. Additionally,
his history of orthopedic injury and total right knee replacement may have impacted
the MCT portion of the test and may explain some of his reported tendency to veer
to the right while walking. The absence of results in this patient's caloric testing
suggests the presence of either a bilateral dysfunction of the lateral semicircular
canals and their afferent pathways, a centrally located lesion or both. Additionally,
abnormal saccade parameters (velocity, accuracy, and latency), reduced optokinetic
gain, and poor qualitative performance during pursuit evaluations suggest involvement
of central system structures.[7] Also of interest is the presence of nonsymptomatic persistent apogeotropic nystagmus
in head/body right and left without fixation. Apogeotropic nystagmus has been reported
in individuals with ischemic changes.[8] In a recent systematic literature review, Macdonald et al[9] reported a lack of consistent reporting of the various types of positional nystagmus
and their underlying causes. In this review, several of the included studies reported
positional horizontal nystagmus, including apogeotropic, in those with a variety of
central system site of lesions. Interestingly 85.4% of subjects in the studies that
reported ocular motor testing had abnormalities including abnormal saccades, smooth
pursuit, and/or gaze-evoked nystagmus.
While it is possible that CM and ITP are not contributing to the patient's symptoms
and vestibular dysfunction, there is some evidence to support their inclusion in the
discussion. Lucieer et al[10] found that a large percentage of bilateral vestibular hypofunction are idiopathic
in nature. A retrospective case study of patients presenting with bilateral vestibular
hypofunction found that nearly 10% of “idiopathic” cases could be attributed to autoimmune
disorders, including Susac's disease and Wegener's disease. Although the prevalence
of chronic ITP in adults is low, it is reasonable to suspect that this autoimmune
disease may be contributing in part to our patient's presentation of bilateral vestibular
hypofunction.
Lucieer et al[10] further identified vascular changes, such as CM, as a definite cause for several
cases of bilateral vestibular hypofunction. CM causes changes in the brain vasculature
which can result in white matter lesions, lacunar infarcts, and microbleeds. These
vascular changes in turn have been noted to impact patient function. As outlined in
a retrospective study by Okroglic et al,[2] 27.8% of patients with documented cases of CM also suffered from gait apraxia. Other
commonly co-occurring clinical symptoms included dementia, stroke symptoms, transient
ischemic attack symptoms, incontinence, vertigo, and seizures.[2]
Further evidence of this need to diagnose CM as early as possible was shown in a study
done by Cerchiai et al,[11] in which they researched possible underlying causes of dizziness in neurovascular
patients. This study identifies CM as “small vessel disease” (SVD). This study examined
60 patients with SVD and categorized them based on neuroimaging results, with either
low- or high-burden SVD. After their categorization, the subjects completed vestibular
testing, and results were analyzed. Researchers found that there was a higher prevalence
of pathological vestibular signs of a peripheral type in patients with lower SVD burden
as compared with those with higher burden SVD. Furthermore, similar to our patient,
a significant canal paresis was found in 12 patients with low-burden SVD, and in two
cases there was evidence of a bilateral vestibular hypofunction. Of note, the two
patients identified with a bilateral vestibular hypofunction, denied exposure to any
vestibulotoxic agents, and were subsequently referred to neurology for further follow-up.
Ultimately, researchers suggested that after a diagnosis of SVD is made, patients
should undergo a complete neuro-otologic evaluation due to the high prevalence of
peripheral vestibular findings in this population.[11] There is a paucity of research specifically focused on ITP's effects on the vestibular
system, making this case study a unique look into the possible effects of CM and ITP
on the vestibular system.
Conclusions
Information available regarding both CM and ITP suggests both disorders as possible
etiologies for this patient's bilateral vestibular hypofunction. ITP is characterized
by autoimmune attacks on the body and it is not beyond belief that the vestibular
system could be victim of one or more of these attacks. It is also common for ITP
to be diagnosed secondary to other disorders such as autoimmune connective tissue
disease as well as acute and chronic infections. Currently, there are no other documented
cases of patients with bilateral vestibular hypofunction and both CM and ITP diagnosis
at this time with which we can compare the results of our patient.
With the incidence of CM and the risk of falling both increasing with age, the importance
of vestibular assessment cannot be overstated in this population. Establishing baseline
performance and documenting changes within the vasculature and the corresponding changes
in vestibular test results may be warranted. Ideally a complete battery of vestibular
diagnostic- and function-based tests including VNG, cervical VEMP, ocular VEMP, vHIT
(all canals), rotary chair, and CDP should be collected to better define site of lesion
in these patients. Ultimately, further research is needed before any concrete statement
can be made regarding both CM and ITP's impacts on the vestibular system specifically
and global balance function. With regards to management, ITP presents an additional
challenge as risk of hemorrhage due to lack of clotting is an unfortunate consequence
if platelet levels fall too low. Fortunately for our patient, he has not to date suffered
a fall that resulted in severe injury and his platelet levels have stabilized. Proper
patient counseling on realistic expectations of postural and balance control with
confirmed bilateral hypofunction should be emphasized particularly with those at increased
risk of incurring major injury secondary to falls.
