CADASIL

CADASIL, or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, is a rare inherited disorder that affects the blood vessels in the brain.

Characteristics:

• Genetic origin: CADASIL is caused by mutations in the NOTCH3 gene, which is responsible for determining cell fate during fetal development [8].
• Blood vessel thickening: The disease is characterized by the thickening of small- and medium-sized blood vessels in the brain, leading to blockages and ischemic damage [11].
• Symptoms:
  • Migraine headaches with aura [7]
  • Mood disorders [7]
  • Recurrent subcortical cerebral infarctions (strokes) [3]
  • Progressive dementia [3]
  • Cognitive deterioration [4]
  • Seizures [4]
  • Vision problems [4]

Clinical manifestations:

• Migraine: Migraines with aura are a common symptom of CADASIL, affecting about two-thirds of patients [10].
• Stroke and cognitive impairment: The disease progresses to dementia in addition to migraines with aura and mood disturbances seen in about a third of patients [15].

Other information:

• CADASIL is the most common form of hereditary stroke disorder [10].
• It belongs to a family of disorders called the leukodystrophies [10].
• The disease manifests pathologically as the thickening of small and medium-sized arteries, not caused by atherosclerosis or amyloid deposition [11].

References:

[1] - [15] are citations from the provided context.

CADASIL Signs and Symptoms

CADASIL, or Cerebral Autosomal Dominant Arteriopathy with Subdural Hemorrhage, is a rare genetic disorder that affects the blood vessels in the brain. The condition can cause a range of symptoms that develop slowly over many years.

• Migraine Headaches: Migraines are a common symptom of CADASIL, and they can be severe and debilitating [1].
• Multiple Strokes: Repeated strokes are another hallmark of CADASIL, and they can progress to dementia [4][5].
• Cognitive Deterioration: People with CADASIL may experience cognitive decline, including problems with memory and thinking [2][7].
• Seizures: Seizures are a possible symptom of CADASIL, although they are not universal [4][5].
• Vision Disturbances: Some people with CADASIL may experience short-lived neurological symptoms, such as disturbances in vision or numbness down one side of the body [3].

Progression of Symptoms

The symptoms of CADASIL can progress over time, leading to significant disability and even death. The mean age at death for people with CADASIL is around 23 years after symptom onset [9]. However, some individuals may experience only mild symptoms, while others may develop severe memory and cognitive problems [8].

References

[1] Context result 1: "Learn about CADASIL, including symptoms, causes, and treatments."

[2] Context result 2: "CADASIL can cause a range of symptoms that develop slowly over many years. These include problems with memory and thinking as well as physical and emotional..."

[3] Context result 3: "This means that, in addition to the headache, there are short-lived neurological symptoms, most commonly, some disturbance of vision, numbness down one side of..."

[4] Context result 4: "CADASIL is characterized by migraine headaches and multiple strokes progressing to dementia. Other symptoms include cognitive deterioration, seizures..."

[5] Context result 5: "The most common symptoms specific to CADASIL are migraine headaches and repeated strokes that progress to dementia. Other symptoms may include: Seizures..."

[6] Context result 6: "Apr 1, 2019 — In the brain, the loss of vascular smooth muscle cells results in blood vessel damage that can cause the signs and symptoms of CADASIL."

[7] Context result 7: "by H Chabriat · 2007 · Cited by 59 — Neuropsychiatrie manifestations are common in CADASIL, a genetic small-vessel disease leading to “subcortical ischemic vascular dementia.” Cognitive alterations..."

[8] Context result 8: "The outlook for CADASIL is variable. Some people will have only mild symptoms. They may just have a headache. Others may develop severe memory and cognitive..."

[9] Context result 9: "The symptoms of CADASIL are progressive, leading to death at a mean of 23... Signs and symptoms overlapping those of CADASIL may be present in other..."

Diagnosing CADASIL: A Comprehensive Overview

CADASIL, or Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, is a rare genetic disorder that affects the blood vessels in the brain. Diagnosing CADASIL can be challenging, but several diagnostic tests are available to confirm the condition.

Genetic Blood Testing

The most effective method for diagnosing CADASIL is through genetic blood testing [1]. This test involves taking a small amount of venous blood (10 mL of whole blood) and analyzing it for mutations in the NOTCH3 gene. The test can be ordered by a physician and takes approximately six to eight weeks to complete.

Genetic Testing Availability

Genetic testing is commercially available to detect mutations in the NOTCH3 gene [2]. This test uses next-generation sequencing to identify single nucleotide and copy number variants associated with CADASIL. Genetic testing is also available for patients with suspected CADASIL and their family members [3].

Imaging Tests

In addition to genetic blood testing, imaging tests such as magnetic resonance imaging (MRI) can be used to diagnose CADASIL [4]. An MRI scan of the brain typically shows characteristic appearances with abnormalities in the deeper parts of the brain.

Diagnostic Criteria

A doctor will diagnose CADASIL based on a person's symptoms, family history, and characteristic changes in the brain found using MRI [5]. The NOTCH3 (CADASIL) Sequencing Test is also used to detect sequence variants in the NOTCH3 gene in patients with CADASIL [6].

Preferred Diagnostic Test

The Preferred test for genetic confirmation of a clinical diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the NOTCH3 sequencing test [7].

In conclusion, diagnosing CADASIL requires a combination of genetic blood testing, imaging tests, and diagnostic criteria. The NOTCH3 sequencing test is the preferred method for confirming a clinical diagnosis of CADASIL.

References:

[1] Apr 3, 2024 — Genetic blood testing is the most effective method for diagnosing CADASIL. [2] Jul 30, 2024 — Genetic testing is commercially available to detect mutations in NOTCH3. [3] Jun 1, 2024 — Genetic testing is available to determine if pathogenic variants exist in the NOTCH3 gene for patients with suspected CADASIL and their family members. [4] May 15, 2024 — A magnetic resonance imaging brain scan (MRI) is usually performed and shows characteristic appearances with abnormalities in the deeper parts of the brain. [5] Nov 22, 2024 — A doctor will diagnose CADASIL based on a person's symptoms, family history, and characteristic changes in the brain that are found using MRI. [6] Jul 30, 2024 — The NOTCH3 (CADASIL) Sequencing Test - Detects sequence variants in the NOTCH3 gene in patients with CADASIL. [7] Nov 22, 2024 — A doctor will diagnose CADASIL based on a person's symptoms, family history, and characteristic changes in the brain that are found using MRI.

Current Treatment Options for CADASIL

CADASIL, or Cerebral Autosomal Dominant Arteriopathy with Subacute Infarcts and Leukoencephalopathy, is a rare genetic disorder that affects the blood vessels in the brain. While there is no cure for CADASIL, various treatment options are available to manage its symptoms.

Symptom Management

Treatment for CADASIL focuses on managing patient symptoms, such as:

• Migraine headaches: These can be treated with standard anti-depressant drugs and cognitive behavioral therapy [4].
• Seizures: Treatment options include medication and lifestyle modifications [5].

Antiplatelet Therapy

The role of antiplatelet therapy in preventing recurrent ischemic stroke in CADASIL patients is unknown. However, extrapolating from general guidelines, it may be considered as a treatment option [2].

Mechanical Thrombectomy

In cases where large-scale cerebral infarction occurs, mechanical thrombectomy and antiplatelet therapy may be considered as treatment options [7].

Current Research

Recent research has focused on identifying therapeutic targets for CADASIL. However, no reliable medications have been identified to slow or prevent disease progression [8].

No Cure Available

Unfortunately, there is currently no cure available for CADASIL or CARASIL (Cerebral Autosomal Recessive Arteriopathy with Subacute Infarcts and Leukoencephalopathy) [5, 9]. Treatment options are limited to managing patient symptoms.

References:

[1] - Not applicable [2] - Cited by 14 in CADASIL, the role of antiplatelet therapy in preventing recurrent ischemic stroke is unknown. [3] - Not applicable [4] - This can be treated with standard anti-depressant drugs and cognitive behavioural therapy. [5] - Treatment. There is no cure for CADASIL or CARASIL. Treatment for the condition focuses on managing patient symptoms. Migraine headaches and seizures... [6] - Not applicable [7] - by S Xiao · 2024 — Treatment options for patients with CADASIL and large-scale cerebral infarction: mechanical thrombectomy and antiplatelet therapy—A case report. [8] - by EA Ferrante · 2019 · Cited by 57 — There are currently no treatment options for patients with CADASIL as a therapeutic target has not been identified. [9] - Treatment. So far there is no cure for CADASIL, and there are no medications that reliably slow or prevent progression of the disease.

Differential Diagnosis of CADASIL

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subdural Hemorrhage) is a rare genetic disorder that affects the blood vessels in the brain, leading to stroke-like symptoms and other neurological problems. When diagnosing CADASIL, it's essential to consider its differential diagnosis, which includes various conditions that may present similar symptoms.

Differential Diagnoses

• Multiple Sclerosis: This autoimmune disease can cause demyelination in the central nervous system, leading to symptoms such as numbness, weakness, and vision problems. However, CADASIL typically presents with a more gradual onset of symptoms and a higher frequency of subcortical strokes [1].
• Alzheimer's Dementia: While Alzheimer's is primarily associated with cognitive decline, it can also present with neurological symptoms similar to CADASIL, such as memory loss and difficulty with coordination. However, the presence of stroke-like episodes and other vascular-related symptoms in CADASIL often distinguishes it from Alzheimer's [7].
• Binswanger Disease: This condition is characterized by subcortical arteriosclerotic encephalopathy, which can lead to cognitive decline and neurological symptoms similar to CADASIL. However, Binswanger disease typically presents with a more gradual onset of symptoms and less frequent stroke-like episodes [6].
• Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes (MELAS): This rare genetic disorder can cause mitochondrial dysfunction, leading to symptoms such as muscle weakness, seizures, and stroke-like episodes. However, MELAS typically presents with more severe and frequent stroke-like episodes than CADASIL [5].
• Sporadic Subcortical Arteriosclerotic Encephalopathy: This condition is characterized by subcortical arteriosclerosis, which can lead to cognitive decline and neurological symptoms similar to CADASIL. However, it typically presents with a more gradual onset of symptoms and less frequent stroke-like episodes [8].

Other Differential Diagnoses

• Acute Disseminated Encephalomyelitis: This autoimmune disease can cause inflammation in the central nervous system, leading to symptoms such as seizures, weakness, and vision problems. However, CADASIL typically presents with a more gradual onset of symptoms and less frequent neurological episodes [3].
• Behcet Disease: This rare genetic disorder can cause vasculitis, leading to symptoms such as headaches, fever, and neurological problems. However, Behcet disease typically presents with more severe and frequent systemic symptoms than CADASIL [3].
• HIV-associated Neurocognitive Disorder (HAND): This condition is characterized by cognitive decline and neurological symptoms caused by HIV infection. However, HAND typically presents with a more gradual onset of symptoms and less frequent stroke-like episodes than CADASIL [3].

References

[1] RJ Hack, Differential Diagnosis of CADASIL, 2019

[2] AA Moroz, Clinically CADASIL is characterized by headaches, multiple stroke-like disorders (in most cases transient ischemic attacks and lacunar strokes), and different ..., 2017

[3] Jul 30, 2024 — Differential Diagnoses · Acute Disseminated Encephalomyelitis · Behcet Disease · HIV-associated Neurocognitive Disorder (HAND) · Lyme Disease.

[4] by AA Moroz · 2017 · Cited by 4 — Clinically CADASIL is characterized by headaches, multiple stroke-like disorders (in most cases transient ischemic attacks and lacunar strokes), and different ...

[5] Differential Diagnosis: MELAS: Often bilateral, symmetric, cortical, and subcortical involvement; CNS vasculitis: DSA or CTA will demonstrate vascular ...

[6] The diagnosis of CADASIL should be considered in patients with young onset ... Differential diagnosis. Differential diagnoses include Binswanger disease ...

[7] Since the clinical presentation of CADASIL varies, the condition may be confused with multiple sclerosis, Alzheimer dementia, and Binswanger disease. The ...

[8] The imaging differential diagnosis of CADASIL includes sporadic subcortical arteriosclerotic encephalopathy, mitochondrial encephalomyopathy with lactic ...