Research status of urinary disorders in cerebral small vessel disease

summary

Urination disorders are considered to be one of the main clinical manifestations of cerebral small vessel disease (CSVD), but it has not received enough attention
from researchers in the past.
Some studies in recent years have shown that the incidence of urination disorders in CSVD patients is high, which seriously affects the daily life and social functioning of
patients.
The clinical characteristics of urination disorders in CSVD patients are mainly manifested as overactive bladder and urinary incontinence, and the mechanism is related to
the damage in the structure and function of the frontal cortex, middle cingulate gyrus, and subcortical circuit.
This article intends to review the clinical occurrence of urination disorders in CSVD patients, and expand new ideas
for the clinical diagnosis and treatment of CSVD.

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Urination disorder is considered to be one of the main clinical manifestations of cerebral small vessel disease (CSVD), which seriously affects the daily life and social functioning of CSVD patients, but it seems that it has not attracted enough attention
from CSVD doctors in the past.
Not only that, the clinical characteristics, pathogenesis, and treatment methods of urination disorders in CSVD patients also need to be further clarified
.
In recent years, the continuous progress of new diagnostic technologies, especially neuroimaging technology, has made CSVD a group of central nervous system diseases of considerable concern, and there have been many new explorations and preliminary answers
to clinical questions related to CSVD.
This article is a review
of the new progress in clinical research on urination disorders in patients with CSVD.

Overview of 1CSVD

CSVD refers to a series of clinical, imaging and pathological syndromes
caused by various causes affecting arterioles, arterioles, capillaries, microvenules and venules in the brain.
According to the imaging diagnostic criteria for the CSVD study published by the Neuroimaging Reporting Standards Group (STRIVEv1) in 2013, the characteristic imaging findings of CSVD include new-onset small subcortical infarction on head MRI, possible vasogenic lacunarity, possible vasogenic white matter hyperintensity, perivascular space, cerebral microhemorrhage, and cerebral atrophy
.
With the advent of the aging society and the improvement of public living standards, the incidence of CSVD patients in China remains high
.
For example, according to recent literature reports, the prevalence of white matter hyperintensity seen in imaging in the elderly population in the community is 65.
4%~72.
1%.

The clinical manifestations of CSVD are complex and diverse, and the currently accepted view is that cognitive dysfunction, movement disorders, affective disorders, urination disorders, and decreased social ability are the most common symptoms, which cause a great burden
on patients and caregivers.
With the development of research, the current research of CSVD symptomatology by domestic and foreign researchers mainly focuses on cognitive impairment, movement disorders, affective disorders, etc.
, but the research on urinary disorders in CSVD patients is still in its infancy, this article reviews the research on urinary function of CSVD patients and provides innovative ideas
for clinical treatment.

2 Urination disorders

Urination disorders can be manifested as urinary tract irritation symptoms such as frequent urination, urgency, urinary incontinence, and nocturia, or urinary tract depression symptoms
such as incomplete urination, fine urinary lines, intermittent urination, and laborious urination.
The bladder, urethra and urethral sphincter are physiologically controlled by a complete and complex neural network on
the spinal cord.
Since the beginning of the new century, the control of urination function by the central nervous system has become a hot spot and focus
of urology research.
With the deepening of research, a series of brain regions including the cortex, cingulate gyrus, and insula have been found to be involved in the regulation of
urination function.
Incomplete structure and function of the central nervous system caused by multiple causes may cause urination disorders, which has become the theoretical basis
for the study of urination disorders in CSVD patients.

3 Study of urination disorders in patients with CSVD

The research on urinary tract irritation symptoms mainly focuses on overactive bladder (OAB) and urinary incontinence, the former is a group of symptoms with urinary urgency as the main clinical manifestations, often accompanied by frequent urination, increased nocturia, urodynamic manifestations are mainly manifested as overactivity
of the bladder detrusor muscle.
Urodynamic studies have found that spontaneous involuntary contraction of the detrusor muscle of the bladder during bladder filling is common in CSVD patients, accounting for 70%~91%.

As one of the main symptoms of OAB, urinary incontinence has been widely valued
in the study of CSVD in recent years.
Similar to the concepts of vascular parkinsonism (VP) and vascular dementia (VD), the emergence of the term "vascular incontinence" also reflects the researchers' in-depth understanding
of the specificity of urinary disorders caused by cerebrovascular diseases, especially cerebral white matter hyperintensity.

In an earlier study, Sakakibara et al.
included 63 elderly patients with varying degrees of white matter damage (male/female = 28/35), with an average age of 73 years (62~75 years old).

The researchers first scored and grouped the participants for white matter damage (1~4 groups) by Fazeka's scoring method, and then divided the subjects' voiding function by questionnaire survey and urinary kinetics, and divided nocturia more than 2 times and urinary incontinence into mild and severe voiding disorders
, respectively.
The results showed that the incidence of nocturia in groups 1~4 was 60%, 58%, 93% and 91% (average 75%), respectively.
The incidence of urge urinary incontinence was 33%, 25%, 57%, and 45% (average 40%)
, respectively.
More importantly, the study found that in elderly patients with white matter impairment, the onset of urinary frequency and urgency may precede the onset
of dementia and gait disorders.
Similar to the results of Sakakibara and other studies on Asian populations, European scholars have also found that more than 50% of elderly CSVD patients have symptoms such as frequent urination, nocturia, and OAB, and there is little difference between men and women
.
Further studies have found that the severity of urination disorders is strongly associated
with lateral paraventricular and subcortical lesions.
Kuchel et al.
completed the analysis of 97 elderly patients (75~89 years old) with community white matter impairment, and used diffused tensor imaging (DTI) to reflect the white matter integration of brain partitions, and correlated analysis
with the urinary incontinence grade measured by the questionnaire.
The results found that up to 64% of the participants had some degree of urinary incontinence
.
The white matter damage brain region most associated with the severity of incontinence is the right inferior frontal gyrus, and white matter fiber tracts in the anterior radial crown and upper frontal occipital bundle may be involved in the development
of urinary incontinence.
Since urinary incontinence is more common in elderly women than in men, Tadic et al.
used functional magnetic resonance technology to observe the correlation between bladder control and white matter damage in elderly women with urinary incontinence patients, and found that the heavier the high signal load of frontal white matter (especially prethalamic radiation and superior longitudinal tract), the worse
the bladder control of patients.

In addition, longitudinal studies have also found that white matter hyperintensity load can explain and predict urination disorders
in the elderly population.
The above studies have shown that urinary incontinence is a common symptom of CSVD in the elderly and is closely related to
the severity of white matter damage.
The researchers did not clarify whether causes such as blood-brain barrier disruption or cerebral hypoperfusion were involved in urination disorders in CSVD patients, but existing studies have confirmed the importance of the integrity of white matter fiber tracts for voiding function, and imaging white matter hyperintensity can predict voiding disorders
in older patients.
Studies have also confirmed that urination disorders such as urinary incontinence can seriously affect the quality of life of
elderly CSVD patients.
In addition, Clarkson et al.
found that pelvic floor muscle training for urinary disorders in CSVD patients found that patients with severe white matter damage load were much less responsive to pelvic floor muscle training than normal people
.
Therefore, the severity of CSVD is directly related to the therapeutic effect
of the patient's urination disorder.

4 Mechanisms of urination disorders in patients with CSVD

Current studies in urology have found that there are three main circuits in the central nervous system that control urination, and these neural circuits are related to sensory cognition, contextualization, control decisions, motor preparation, and participate in the normal completion
of urination.
Loop 1: The frontal cortex circuit, which mainly includes the medial prefrontal cortex (mPFC), mainly controls bladder filling and discharge through conscious control or preconscious awareness, and decides whether to urinate
through the contextualization of integrated information.
Loop 2: The middle cingulate loop, which mainly includes the dorsal anterior cingulate gyrus and the adjacent auxiliary motor cortex, is mainly responsible for integrating bladder sensory information and motor reflex preparation
.
Loop 3: The subcortical circuit, which mainly includes the hippocampus and related limbic systems, is mainly responsible for environmental cognition and emotional regulation
related to urinary status.
When CSVD patients have impairment in the structure and function of the above circuits, corresponding urination disorders
occur.
In fact, many researchers have found that CSVD patients often have other clinical symptoms
while having urination disorders.
For example, in a cross-sectional study, Haruta et al.
included 40 elderly patients with white matter impairment with urination disorders, and evaluated the correlation between cognitive function and voiding disorders, including the Mini-mental State Examination (MMSE) and the Frontal Assessment Battery (FAB), and found that overactivity of the detrusor muscle of the bladder was indeed associated with Go/ The No-Go test is closely related to
the decline in inhibition control ability.
Therefore, the investigators believe that this result can be explained by impaired control decisions related to urination caused by prefrontal cortex involvement in CSVD patients, and is also reflected in
the FAB test.

5 Treatment of urination disorders in patients with CSVD

The treatment of urination disorders in CSVD patients is more likely to be anticholinergic drugs such as solifenacin and midanacin, mainly because most elderly patients have varying degrees of parasympathetic nerve excitement, but the adverse reactions of anticholinergic drugs for cognitive impairment may affect normal voiding control, and the adverse reactions of such drugs are more serious
in the case of common blood-brain barrier damage in CSVD patients.
Therefore, in recent years, based on the clinical and mechanistic research of urination disorders in CSVD patients, the application of cerebrovascular protective agents or antihypertensive, lipid-lowering and other treatments to improve cerebral small blood vessel function is a useful supplement
.

6 Outlook

CSVD is a common disease in middle-aged and elderly people, and compared with other symptoms, the research on urination disorders in CSVD patients is far behind
.
It is not yet possible to distinguish between urinary disorders that are central nervous system or urinary
system.
The author believes that similar to the concept of "CSVD-related dizziness", if the direction of future research can be made in "CSVD-related urination disorders", the diagnosis and treatment of urination disorders in CSVD patients will be more targeted, which will be of great benefit
to solving the problem of urination disorders in CSVD patients.