Binswanger’s Disease (BD)

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About Binswanger’s Disease (BD)

Binswanger’s disease (BD), also called subcortical vascular dementia, is a type of dementia caused by widespread, microscopic areas of damage to the deep layers of white matter in the brain. The damage is the result of the thickening and narrowing (atherosclerosis) of arteries that feed the subcortical areas of the brain.

Atherosclerosis (commonly known as “hardening of the arteries”) is a systemic process that affects blood vessels throughout the body. It begins late in the fourth decade of life and increases in severity with age. As the arteries become more and more narrowed, the blood supplied by those arteries decreases and brain tissue dies.

A characteristic pattern of BD-damaged brain tissue can be seen with modern brain imaging techniques such as CT scans or magnetic resonance imaging (MRI). The symptoms associated with BD are related to the disruption of subcortical neural circuits that control what neuroscientists callexecutive cognitive functioning: short-term memory, organization, mood, the regulation of attention, the ability to act or make decisions, and appropriate behavior.

Binswanger’s disease (BD) is a progressive form of cerebral small vessel disease (SVD) affecting the white matter (WM) and other subcortical structures. Advances in imaging have increased interest in understanding has arisen in the definitions, clinical presentations, differential diagnoses, risk factors and complications of BD.

Clinical and imaging features, neurophyschological profile and cerebrospinal fluid analysis aid in making the diagnosis. With recent developments in MRI methods and analysis of CSF and blood biomarkers, we have gained a greater understanding of the complex pathophysiology of the disease, which has helped with the diagnosis and prognosis of BD.

There is growing evidence that the WM injury in BD is related to endothelial dysfunction with secondary inflammatory response leading to breakdown of the neurovascular unit (NVU). This review summarizes current and future research directions, including pathophysiological mechanisms and potential therapeutic approaches.

The most characteristic feature of BD is psychomotor slowness – an increase in the length of time it takes, for example, for the fingers to turn the thought of a letter into the shape of a letter on a piece of paper.

Other symptoms include forgetfulness (but not as severe as the forgetfulness of Alzheimer’s disease), changes in speech, an unsteady gait, clumsiness or frequent falls, changes in personality or mood (most likely in the form of apathy, irritability, and depression), and urinary symptoms that aren’t caused by urological disease. Brain imaging, which reveals the characteristic brain lesions of BD, is essential for a positive diagnosis.

Binswanger's Disease (BD)

Binswanger’s Disease (BD)

 

Binswanger disease is a progressive neurological disorder caused by arteriosclerosis and thromboembolism affecting the blood vessels that supply the white-matter and deep structures of the brain (basal ganglia and thalamus).

Most patients experience progressive loss of memory and intellectual abilities (dementia), urinary urgency or incontinence, and an abnormally slow, shuffling, unsteady pattern of walking, usually over a 5-10 year period. Due to their vascular etiology, the symptoms and physical findings associated with Binswanger disease may suddenly worsen due to stroke, stabilize and then improve for a brief time, but the patient’s overall condition continues to progress as the blood vessels become increasingly obstructed.

Symptoms

Affected individuals often become depressed, uncaring (apathetic), inactive, and unable to act or make decisions (abulic). They become withdrawn, and exhibit poor judgement and less spontaneous communication. In addition, affected individuals may have difficulty with speech (dysarthria), swallowing (dysphagia), and urinary bladder control (incontinence). Some patients exhibit abnormalities that are similar to those seen in Parkinson disease, such as slowness, poor balance and short, shuffling steps (Parkinsonism). Tremor is usually not a feature.

Many individuals with Binswanger disease have a history of strokes or transient ischemic attacks. Consequently, the symptoms and signs of this disease develop in a stuttering or stepwise fashion; in contrast to the insidious, gradually progressive course of neurodegenerative diseases (see Related Disorders).

The symptoms of Binswanger’s disease are due to disruption of the subcortical neural areas. The most commonly encountered symptoms include psychomotor slowness.

Symptoms related to cognitive functioning includes:

  • Short term memory loss and mental deterioration.
  • Mood disorder including apathy, depression and irritability.
  • Difficulty with organization and regulation of attention.
  • Inability to act or make appropriate decision.
  • Behavioural issues.

Other symptoms of Binswanger’s disease include:

  • Speech difficulties.
  • Language issues.
  • Unsteady balance and gait.
  • Frequent falls and clumsiness.
  • Changes in personality.
  • Urinary disturbances such as uncontrollable bladder.
  • Transient ischemic attack.
  • Muscle ataxia.
  • Slow movements.
  • Postural changes.
  • Frequent episodes of fainting.

Causes

Binswanger disease is caused by atherosclerosis, thromboembolism and other diseases that obstruct blood vessels that supply the deep structures of the brain. Hypertension, smoking, hypercholesterolemia, heart disease and diabetes mellitus are risk factors for Binswanger disease. Rare hereditary diseases such as CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) also cause Binswanger disease. Thus, Binswanger disease is actually a clinical syndrome of vascular dementia with multiple causes, not a specific disease.

Diagnosis

The diagnosis of Binswanger disease is usually based on a thorough clinical evaluation, including a detailed patient history, physical examination, and magnetic resonance imaging (MRI) or computerized tomography (CT) scanning of the brain. MRI and CT reveal nerve fiber (white matter) degeneration and multiple small strokes in the deep structures of the brain.

Diagnosis of Binswanger’s disease is done after obtaining a detailed case history followed by clinical examination. Investigative studies such as CT scan, MRI and proton MR spectrography are done as confirmatory tests. CT scan and MRI of brain show a characteristic pattern of Binswanger’s disease damages to brain tissue. Indicative signs include presence of infarction, lesions, loss of intensity of central white matter, enlargement of ventricles and leukoaraiosis.

Leukoaraiosis or LA is an imaging finding of the white matter that is commonly found in imagining tests of patients with Binswanger’s disease. This finding is found in other neurological conditions as well and thus cannot be taken as a confirmatory sign.

A Mini Mental Test (MMT) is usually done for assessment of cognitive impairment and vascular dementia. The condition is best diagnosed by a team of experts which includes experienced neurologist and psychiatrist to have in depth understanding of the condition and thus can rule out other neurological or psychological conditions.

Treatment

The American Heart Association (AHA) recently published treatment guidelines for patients with VCI. Nevertheless, there are no specific clinical studies targeting therapies for BD, making it difficult to choose treatments for this group of patients. Although most studies that use subjects with VCI, vascular dementia and leukoaraiosis have included BD patients, they have not been specifically targeted for treatment trials.

Therefore the real treatment effect of a specific therapy is still unknown. Despite the lack of rigorous studies, best treatments can still be inferred and generalized from multiple studies. Here we review treatments that aim to prevent progression, improve behavior and reduce complications.

Blood Pressure Reduction

Hypertension plays a central role in the pathogenesis of BD. Hypertension is a major risk factor for all types of symptomatic strokes, asymptomatic strokes and WMHs. Blood pressure control reduces the incidence of stroke in both primary and secondary prevention. There is compelling evidence that treatment of hypertension is beneficial in patients with SVD.

Lacunar strokes are prevented with blood pressure control but the BP target is still debatable. Tight BP control (SPB<130) is emerging as more effective than less intense therapy (SBP 140-130) for stroke prevention. The recent secondary prevention of small subcortical stroke trial (SPS3) trial compared both BP regimens for secondary prevention in lacunar strokes but did not reach statistical significance.

Hypertension has consistently been associated with cross-sectional measured WML burden and with longitudinally measured WML progression.

In longitudinal studies, rogression of WMHs is associated with uncontrolled hypertension and hypertension treatment reduces the growth of WMHs. To date two randomized, placebo-controlled trials have been performed to investigate the effect of antihypertensive treatment on the progression of WML; the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) and the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial.

The PROGRESS achieved a small significant decrease of WMHs on brain MRI with large reduction in BP compare to placebo (mean SBP reduction: 9.5 mmHg). In the PRoFESS the reduction of BP was modest (mean SBP reduction: 3.3 mmHg) and no significant changes in WMH was observed.  Two recent observational studies found treatment of people with high systolic blood pressure to be related to less WML progression.

Blood pressure control has also proved to reduce progression of cognitive impairment and onset of dementia associated with stroke and WMHs.  We recommend an aggressive management of hypertension especially in younger patients who can tolerate lower BP levels better than older ones. Older patients should be treated with hypertensive medications although targeting low BP levels is in this group is still controversial.

Antiplatelet therapy

The use of antiplatelet therapy is recommended based on the presence of lacunar strokes. Dual antiplatelet therapy is not recommended. In the SPS3 the use of dual antiplatelet therapy did not reduce recurrence of ischemic stroke outcomes and increased the rate of intracranial hemorrhages (ICH) in that patient population.

 There is scarce evidence in the use of antiplatelets in patients with isolated WMHs or BD in the absence of clinical or radiological strokes. There is a 3 times higher risk of stroke in subjects with WMHs than in the general population.

 BD carries a higher risk of ICH; therefore the benefit of ASA for stroke primary prevention versus the risk of increasing ICH in this group is unknown. Despite of the limitations, the use of antiplatelet therapy BD with radiological evidence of ischemic stroke seems reasonable. However, it is important to avoid treating patients without symptomatic stroke or TIA and amyloid angiopathy or other mimic conditions that could carry a higher risk of ICH.

Statins

Statins play a very important role in secondary stroke prevention. Statins have many pleotropic properties such as reduction of atherosclerosis and inflammation. Makers of endothelial dysfunction and vascular inflammation are common finding on patients with BD and SVD. However the use of statins is not certain in BD patients with no history of clinical stroke or imaging confirmed stroke. The recent AHA guidelines recommends the use of statins in patients with high risk of stroke as primary prevention.

We recommend for the use of statins in BD patients with history of stroke or TIA, radiological stroke and an LDL >100mg/dl. Because statins might somewhat increase the risk of ICH in patients with SVD more information is required to understand how intensive the treatment should be.

Physical Activity

Physical activity prevents cognitive impairment in normal aging and reduces the speed of cognitive decline in patients with mild cognitive impairment (MCI).

Physical activity in participants with SVD is related to WMHs volume on conventional FLAIR and to WM microstructural integrity using WM MRI tractography analysis. In large cohort of patients with leukoaraiosis from the LADIS group, physical activity reduced the risk for cognitive impairment and vascular dementia, independently of the severity of the WM lesions.

The benefits of exercise and physical activity for stroke prevention and hypertension treatment of are also well stated. Theoretical benefits of physical activity on the pathophysiology of the disease are multiple: reduction of blood pressure, anti-inflammatory, increase of oxygen capacity, etc.

The type (aerobic versus resistance) and amount of recommended exercise are still debated and an ongoing matter of study. Although resistance exercises (e.g. weight lifting) might have potential benefits, most of the human and animals studies have focused on the effects of aerobic exercise in cognition. Therefore, there is more evidence to recommend aerobic exercise for prevention of BD.

Diet

High homocysteine levels are associated with risk of stroke and SVD. However there is no benefit of folic acid or vitamin supplements for the prevention of stroke, WHMs or improvement of cognitive function. We recommend a low salt diet. A normal American diet has 3.5 to 4 gms of sodium per day.

A high salt diet raises blood pressure and increases the risk of stroke. Salt reduction plays an important role on reduction of blood pressure. The American heart association recommends only 1.5 grams of sodium in patients with stroke. High sodium intake is also linked to increase in oxidative stress and worsen of vascular resistance. However, the specifics of the role of salt and Binswanger’s pathology remain to be studied.

Physical Therapy and Rehabilitation

Patients with BD often have balance problems and parkinsonian features. The initiation of an exercise program should be preceded by a full evaluation of physical therapy and programing. Although the evidence of physical therapy as an effective treatment is unclear, it encourages patients to participate in physical activities, understanding their risks and limitations. Yoga and tai-chi most likely are beneficial, but studies are still needed.

Management of other medical conditions

Diabetes does not appear to be at the root of the BD pathology, but it is suspected to contribute to the worsening of the disease. Glucose control is recommended but tight glucose control should be avoided due to the detrimental effects of hypoglycemic events.

Restoring impaired vision and hearing helps to restore well-being in aging and demented patients in general. Hearing loss is independently associated with accelerated cognitive decline and incident cognitive impairment in older adults. Although still unclear that improvement of hearing with devices will affect cognitive decline.

Acetylcholinesterase inhibitors and Memantine

Autopsy studies have demonstrated cholinergic deficits in patients with VCI.

Several large clinical trials have examined the effect of cholinesterease inhibitors. Patients with VCI who received galantamine showed improved cognitive performance compared with placebo, though functional measures were unchanged.

In another double-blind placebo controlled trial of donepezil for VaD, statistically significant gains occurred for cognitive outcomes, dementia severely and global clinical-based improvement ratings.

However, favorable effects in functional status were again not obtained. In fact, only one study to date has reported benefits for activities of daily living. Another placebo-controlled study compared donepezil to placebo in patients with CADASIL.

No significant effect was found on the primary outcome measure, though treatment improved some secondary endpoints. The lack of benefits for functional outcomes or dementia severity gain indicated uncertain clinical efficacy, a conclusion reinforced in a recent metanalysis.

Relatively less is published about treatment of VCI patients with memantine, an N-methyl –D – aspartate antagonist approved for moderate to severe AD. Two large, placebo-controlled studies found statistically significant drug-placebo differences in cognitive outcome measures.[58] No effect on global or functional outcomes was demonstrated, however, undermining their clinical significance in a manner to cholinesterase inhibitors.

In conclusion human studies with cholinergic medications and memantine have not shown a well-defined clinical improvement and in our experience these medications might cause side effects and discomforts. These medications are not FDA approved in VCI or VaD patients and in general we do not recommend its widespread use in VCI or mixed dementia when the vascular component appears to be the primary cause.

Medications to avoid

There is some evidence that blood pressure variability and systolic spikes can decompensate patients and increase risk of vascular events. ICH is also more common on patients with SVD and BD and can be potentially trigger by fluctuations of BP. In our experience we try to avoid medications that can cause rebound hypertension or hypertensive surges. We try to avoid medications that can cause confusion, drowsiness and psychosis especially in BD with severe cognitive impairment or dementia.

Because parkinsonism is a common BD finding, neuroleptics, prokinetic agents and medications that can worse parkinsonism should be used with caution.

Anticoagulation, especially with warfarin, should be considered only in atrial fibrillation, valve replacement or high-risk patients. There is a strong association with warfarin therapy and symptomatic ICH inpatients with severe WMHs. The Stroke Prevention in Reversible Ischemia Trail (SPIRIT) used an INR target of and found that WMHs was a strong independent risk factor for ICH, with an odds ratio of The results were replicated in a hospital-based case-control, in which patients with a mean of INR of had an odds ratio of for symptomatic ICH.

Recovery and rehabilitation

Although currently no cure exists for dementias such as the Binswanger type, the goal of therapy is to maintain the highest state of physical health by managing the symptoms, along with maintaining the highest possible state of functional activity and well being. In addition to physical and occupational therapy, treatment for mood swings or depression helps the person with Binswanger disease to remain active, socially engaged, and mobile for as long as possible.

When the disease progresses and mobility, along with mental ability, decreases, the person with Binswanger or

Other dementias will likely require a nurturing environment that provides for medical care and safety. Whether at home or in a care facility, personal care assistance may be necessary for many or all hours of the day.

Many communities have adult daycare centers with targeted, stimulating activities for persons with dementia in the early stages. Long-term care facilities that specialize in dementia can provide an environment that fosters mobility in a soothing environment, where staff provides cues to orient the person with dementia to memories and surroundings.

Causes and Risk Factors for Binswanger’s Disease

Binswanger disease is primarily caused by atherosclerosis, thromboembolism and disorders in the blood vessels that supply the deep tissues of the brain. Other predisposing risk factors of Binswanger’s disease include elevated cholesterol levels, heart disorders, diabetes, elevated blood pressure and history of smoking.

Certain rare hereditary diseases such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) may also lead to Binswanger’s disease. Binswanger’s disease is not a specific disease. It is a clinical syndrome of a vascular dementia with multiple causes.

A risk factor is something that increases your chances of getting a disease or condition. Binswanger’s disease usually affects people over the age of 60. Other exact risk factors for the disease are unknown. However, factors that are believed to increase the risk of the disease include:

  • High blood pressure
  • Cardiovascular disease
  • Hardening of blood vessels (atherosclerosis)
  • Diabetes

Prevention

There are no definitive guidelines for the prevention of Binswanger’s disease because the exact cause is unknown. However, the following may help reduce your risk:

  • Don’t smoke. If you smoke, quit.
  • Eat a diet that is low in fat and low in salt.
  • If you drink alcohol, do so only in moderation. Moderate alcohol intake is two drinks per day for men and one drink per day for women.
  • Have your blood pressure and blood cholesterol levels checked regularly (at least once per year) , and if treatment is recommended follow your doctor’s guidelines.
  • Avoid low blood pressure. If you get dizzy when you stand up or have a history of fainting, be sure to talk with your doctor about ways to ensure a safe amount of blood circulation for your brain at all times.
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