Dizziness/vertigo associated with cerebral small vessel disease

Cerebral small vessel disease

Cerebral small vessel disease (CSVD) refers to a series of clinical, imaging and pathological syndromes
caused by cerebral perforatorial arteries and their distal branches, arterioles, capillaries, venules and microvenous lesions 。 Its clinical manifestations mainly include stroke, cognitive and emotional disorders, balanced gait disorders, mental changes and decreased life ability, and imaging manifestations include lacunar infarction (LI), white matter hyperintensities (WMHs), perivascular space enlargement (EPVS), cerebral microbleeds (CMBs) and cerebral atrophy
。 Common forms of dizziness and vertigo are instability and presyncope state such as head drowsiness, lightheadedness, visual rotation or self-perceived rotation, movement, shaking; Gait instability and balance disturbances are also often associated with dizziness, especially in older patients with
CSVD.
Vascular lesions and neurological lesions represented by CSVD are closely related
to dizziness/vertigo in terms of symptoms, anatomy, pathology and biochemistry.
The relationship between CSVD and dizziness/vertigo has received increasing attention
in recent years.

Association of CSVD with dizziness/vertigo

Connection of clinical symptoms In patients with vascular risk factors such as dizziness, vertigo, gait instability, balance disorders, and a long-term history of hypertension, MRI often reveals deep WMHs and other abnormal changes
in small blood vessels.
Researchers have explored whether there is a correlation between the two and found that cerebrovascular disease is closely related to vertigo, about 50% of patients with vasculitic syndrome have vertigo, and vascular inflammation can promote WMHs and LI.

A retrospective study of 223 CSVD patients by Okroglic et al.
showed that 17% of patients had vertigo symptoms, and frontal lobe and basal ganglia WMHs and LI were closely related to
vertigo symptoms.
Ahmad et al.
divided 122 patients with dizziness/vertigo into an unexplained group and a clear diagnosis group (including benign paroxysmal positional vertigo, vestibular neuritis, vestibular migraine, Meniere's disease, bilateral vestibular dysfunction, orthostatic hypotension, cerebellar ataxia, etc.
), and applied the Fazekas scale to assess the severity
of WMHs.
The results showed that the proportion of severe WMHs (Fazekas grade 2 or 3) in the unexplained group was significantly higher than that in the diagnostically definite group, the proportion of rotational vertigo was also significantly higher than that in the diagnostically definite group, and gait and postural abnormalities were more common
.
Vertigo attacks come in different forms, and discomfort, imbalance, and increased dizziness in moving scenes and noisy crowds are called visual vertigo
.
Pollak et al.
included patients with visual vertigo with symptoms persisting for more than 3 months as the experimental group, and patients with dizziness without visual vertigo symptoms as the control group, and the results showed that multiple WMHs may promote the occurrence
of visual vertigo.

CMBs are clinically characterized by stroke, cognition, and affective impairment
.
Previous studies in patients with dementia have shown that cerebral amyloid angiosis (CAA) is an important cause of
CMBs.
Whether CMBs directly cause dizziness/vertigo episodes and the corresponding mechanism are unclear, and a cross-sectional study showed no significant association between CMBs and dizziness/vertigo, but the attention deficit, visuospatial memory abnormalities, and executive dysfunction that often accompany patients with CMBs can exacerbate pre-existing dizziness/vertigo symptoms
.
Cerebral atrophy is independently related to dizziness left after symptom relief in patients with benign paroxysmal positional vertigo, and may be related to
vestibular neuropathy.
In addition, brain atrophy in older people can affect vision, proprioception, and coordination of the vestibular system, leading to dizziness/vertigo
.
Clinical reports on the relationship between LI and EPVS and dizziness/vertigo are relatively rare, and animal experiments have shown a certain correlation
between EPVS and cognitive impairment and depression.

Anatomical site connection There is a clear association between the anatomical site of the lesion and clinical symptoms, so CSVD lesions in some anatomical sites can cause dizziness/vertigo
.
Studies by Okroglic et al.
have shown that frontal WMHs and LI can lead to frequent episodes
of vertigo.
Studies by Zhao Hongyi et al.
showed that WMHs in vertigo patients were more common in the frontal lobe, followed by the parietal, occipital and temporal lobes; WMHs in patients with dizziness are more common in the parietal and occipital lobes, followed by the frontal and temporal lobes; WMHs are more common in patients with balance disorders in the subcurtain and frontal lobes
.
Based on the results of clinical studies in recent years, it is suggested that vertigo is closely related to vestibular lesions of the frontal lobe, and dizziness is mostly caused by
ischemic cerebrovascular lesions.
In order to clarify the relationship between vestibular lesions and cerebrovascular disease and dizziness/vertigo, Cerchiai et al.
performed vestibular function measurement
on 60 patients with small vessel white matter disease (SVD) with dizziness 。 The results showed that the incidence of peripheral vestibular dysfunction in the low SVD burden (L-SVD) group was significantly higher than that in the high SVD burden group (H-SVD) (51.
6% vs.
17.
2%; P=0.
012); the proportion of unexplained dizziness was as high as 82.
8%
in the H-SVD group.
Therefore, not only do patients with H-SVD have a high risk of dizziness, but also patients with L-SVD should pay special attention to the prevention and treatment
of peripheral vestibular diseases.
Yeo et al.
showed that parieto-insular vestibular cortex (PIVC) infarction affects the information transmission pathway between the vestibular nucleus and cortex, and diffusion tensor imaging (DTI) examination shows damage
to the vestibular core pathway.

In summary, frontal WMHs are clearly associated with vertigo episodes, while parietal-occipital WMHs can lead to frequent dizziness
.
H-SVD often indicates the presence
of central dizziness.
PIVC infarction impairs its information pathway to the vestibular nucleus, and vertigo episodes are significantly increased
.

Possible mechanisms by which CSVD promotes dizziness/vertigo

WMHs cause conductive fibropathies WMHs in the cortical region often involve subcortical tracts, resulting in decreased cone and extrapyramidal function, walking instability, and decreased
balance.
One hypothetical mechanism is that when WMHs involve the subcortical region responsible for feedback inhibition, an excessive vestibular response to a form of visual stimulus, known as visual vertigo
, occurs.
Studies of WMHs-associated vascular vertigo suggest that WMHs may affect neural networks that connect the vestibular cortex, such as nerve fibers between the prefrontal lobe and the vestibule, leading to vertigo and dyskinesia
.

The fibrous tracts of deep white matter govern lower limb movement and play an important role
in gait and balance regulation.
A cross-sectional analysis showed that CSVD-related changes in brain microstructure affect upper and lower limb motor performance, especially WMHs and brain atrophy are strongly associated with deterioration of motor function, and WMHs-induced balance disorders, gait instability, and eye movement abnormalities can also cause or worsen dizziness/vertigo
.
One view is that decreased vestibular Sylvian region and PIVC blood supply after subcortical infarction, and lesions such as WMHs and LI due to hypoperfusion and secondary ischemic hypoxia are common causes of typical vestibular symptoms, manifesting as dizziness, spinning vertigo without nystagmus, gait instability, and falls
.
Another view is that patients with CSVD have disconnected cortico-cortical syndrome, which in turn causes white matter tract damage that controls gait and balance, and can also produce subjective feelings
such as instability and dizziness/vertigo.
The above research data suggest that WMHs-induced vestibular dysfunction and nerve conduction pathway disorders are the main causes of dizziness/vertigo, and that balance and gait disturbances secondary to WMHs and subcortical infarction can also cause or worsen dizziness/vertigo
.

EPVS and inflammatory cell infiltration Patients with a large number of EPVS in the basal ganglia area often show a certain degree of cognitive impairment, and some patients have gait abnormalities
.
Normally, the perivascular space (PVS) is filled by cerebrospinal fluid (CSF), which enters the subarachnoid space and then passes through the lymphatic pathway to the cervical lymph nodes
.
When the lymphatic circulation pathway of the brain is obstructed or product transport is impaired, EPVS
appears around the ventricles.
At this time, water-soluble mucopolysaccharides accumulate in PVS and cause infiltration of inflammatory cells, resulting in some cerebrovascular lesions and neurodegeneration of the nervous system, which may be related to
the occurrence of dizziness/vertigo.

Age-related CSVD and vestibular dysfunction Common risk factors for CSVD include age, diabetes, hypertension, smoking, alcoholism, hypercholesterolemia, etc.
, which are also prone to atherosclerosis
.
Atherosclerosis can cause vertebrobasilar artery tortuosis or stenosis, leading to dizziness/vertigo associated with posterior
circulation ischaemic events.
In addition, older patients may have both large and small vessel lesions
.
When considering CSVD-related dizziness/vertigo, attention should also be paid to whether concomitant macrovascular lesions are a contributing factor
.
Dysfunction of cerebrovascular autoregulation is also an important factor in
the involvement of WMHs and the structural integrity of white matter.
Disorders of blood flow in small blood vessels around the inner ear in older people cause poor arterial anastomosis, which may cause a decrease
in the number of vestibular neurons.
In addition, with age, the number of vestibular nuclei, ganglia, and peripheral nerve fibers in the vestibular system decreases significantly, and vestibular function decreases, which may be associated
with nonspecific dizziness/vertigo symptoms in older CSVD patients.
Therefore, before attributing dizziness/vertigo symptoms to CSVD, it is first necessary to identify peripheral vestibular disease in detail and prevent the underlying disease
.

CSVD - Psychopsyche - Dizziness/Vertigo Mode Dizziness/vertigo is a common symptom
in patients with anxiety, depression, and physical imbalance.
When balance disorders and acute vestibular symptoms occur, the body quickly returns to normal
through physical and behavioral adaptation mechanisms.
In some patients with anxiety, this adaptive mechanism persists, resulting in dysposture, gait, gaze, and maladaptation, leading to functional dizziness
.
These abnormal adjustment mechanisms are also one of
the common causes of visual vertigo, persistent postural perception dizziness, and chronic subjective dizziness.
Imaging studies show a high prevalence of frontal WMHs in patients with vascular vertigo, suggesting that frontal WMHs may be related to
vestibular dysfunction and anxiety.
Other studies have shown complex interactions between mental disorders and vestibular symptoms, and neuroanatomical and functional overlaps
between anxiety and the vestibular system.
Many neuronal pathways link the vestibular network to limbic structures, and the vestibular cortex regulates anxiety
through its connection to the amygdala.
When WMHs cause vestibular impairment, the resulting anxiety disorder can exacerbate the maladaptive conditions described above, leading to chronic dizziness for a long time
.
The vicious cycle of "pathological-psychopsycho-symptomatic" caused by this indirect pattern (CSVD-vestibular-anxiety/depression-dizziness/vertigo) cannot be ignored
in particular.

Macrovascular/small vessel disease associated with dizziness/vertigo Macrovascular lesions often coexist
with CSVD.
For example, patients with large artery atherosclerotic (LAA) often have varying degrees of CSVD, and patients with LAA with moderate to severe CSVD have a significantly increased
risk of recurrence of ischemic stroke and intracerebral hemorrhage.
In addition, intracranial atherosclerosis is also closely related to
local perforatorial occlusion.
Vertigo
can also be caused by posterior fossa vascular malformations, prolonged dilation of the vertebrobasilar artery, or hypoplasia due to distal insufficiency, or compression of the vestibular nerve.

Macrovascular pathological changes and morphological changes can eventually lead to CSVD lesions, and a variety of inflammatory factors (eg, serum cystatin C, interleukin-6) and pathological changes (eg, vascular endothelial dysfunction, hypoperfusion) that cause macrovascular lesions can also cause abnormal
small vessel function.
Hypoperfusion of large and small vessels is a common cause
of dizziness/vertigo.
For example, anterior inferior cerebellar artery ischemia can cause ischemic lesions of the inner ear, leading to vertigo; Solitary dizziness/vertigo can be caused by vestibular nucleus ischemia and small brainstem infarction; Middle cerebral artery infarction causes distal small vessel ischemic lesions, and PIVC can lead to central vestibular access disorders, and typical vestibular symptoms
such as dizziness and imbalance may occur.
Vertigo-related intracerebral hemorrhage is also concentrated in the posterior circulation, especially cerebellar hemorrhage can manifest as severe vertigo
.
Due to the close connection between macrovascular and small-vessel lesions, the treatment of macrovascular lesions should also be paid attention to in the prevention and treatment
of CSVD-related dizziness/vertigo.

Diagnosis and differential diagnosis of CSVD-related dizziness/vertigo

In patients with sudden onset of dizziness or vertigo, the first step is to differentiate central or peripheral vestibular lesions
.
Due to the variety of types and symptoms of peripheral vestibular lesions, a thorough history and physical examination are first required to confirm the diagnosis, such as neurological examination, head shake test, ocular deviation response, nystagmus, follow-up test, saccade test, vestibular oculomotor reflex, fixed vision suppression, fixed vision metastasis, position test, etc
.
Central vestibular lesions
are usually differentiated by clinical symptoms, imaging, and/or blood biochemistry.
In recent years, it has become easier to detect cortical microinfarcts using 7.
0T MRI, and the results are consistent with pathology, which is helpful to establish the association between
CSVD and dizziness/vertigo.
Vestibular examination results are highly
sensitive and specific for differentiating peripheral vestibular disease (eg, vestibular neuritis, Meniere's disease) and central vestibular disease (eg, vestibular migraine, posterior circulation ischemia).
In cases where suspicion of central vertigo is high and early diffusion-weighted imaging is negative, vestibular examination can help identify central vertigo
if peripheral lesions are excluded, combined with clinical signs.
When patients with dizziness/vertigo have concurrent CVSD imaging changes, they need to be differentiated
by vestibular examination.
For patients who cannot clearly link the two, dynamic follow-up should be followed
.

In clinical practice, even if CSVD imaging features are found on MRI of the head, its association
with dizziness/vertigo should be interpreted with caution.
Studies by Cerchiai et al.
showed that the proportion of peripheral blood vestibular abnormalities in elderly patients whose main complaints were chronic dizziness or instability and WMHs were found on head MRI was as high as 35% after detailed vestibular function evaluation, while the proportion of peripheral vestibular disease in the mild WMHs (Fakezas grade 1) group could be as high as 50%.

Therefore, in some patients with chronic chronic dizziness, even if CSVD is found on imaging, a detailed history and physical examination, along with vestibular function assessment, are required to determine the underlying cause
.

For patients with CSVD-related dizziness/vertigo, the severity of the lesion can be graded to help develop a more precise treatment plan
.
For example, there are a variety of qualitative and quantitative methods for WMHs, including the Fazeka Visual Scoring Scale, the Scheltens Scale, and the Age-Related White Matter Change (ARWMC) scale, and computer-automated analysis including the FreeSurfer method and the Support Vector Machines (SVM) method
。 For patients with a high (severe) CSVD score, dizziness/vertigo degree should be assessed at the same time to observe the relationship
.
Dizziness Handicap Inventory (DHI) is an effective scale for evaluating the symptoms of vertigo in patients, which can simultaneously evaluate the physical, functional and emotional domains, combined with the visual grading score of vertigo degree, which can more accurately understand the patient's condition, provide ideas for the next study of the association between dizziness/vertigo and CSVD, and also help to formulate individualized rehabilitation plans
.

epilogue

CSVD promotes dizziness/vertigo
through mechanisms such as nerve pathway damage, inflammatory infiltrative injury, age-related vestibular degeneration, psychopsychiatric, and hypoperfusion associated with macrovascular and small vessel disease.
However, the identification and treatment of CSVD-associated dizziness/vertigo still needs to be further explored and reached a consensus
.
Therefore, various clinical and basic studies need to be actively carried out around the pathophysiology, risk factor identification, clinicopathology and imaging features of CSVD-related dizziness/vertigo, so as to better understand the association and mechanism
between CSVD and dizziness/vertigo.