Overview
Autosomal recessive cerebral arteriopathy and atherosclerosis with subcortical infarcts and leukoencephalopathy (CARASIL), or Maeda syndrome, is prevalent in young adults and is characterized by baldness, low back pain, and leukoencephalopathy; it is also referred to as youth-onset Binswanger-like leukoencephalopathy. It is a familial non-atherosclerotic, non-amyloid cerebral small-vessel disease caused by mutations in the HTRA1 gene on chromosome 10.
Etiology.
The disease is caused by a mutation in the HTRA1 gene on chromosome 10, which encodes the Htra1 serine protease with decreased activity, affecting its intracellular signaling and thus causing pathological changes such as fibrous thickening of the intima of the small arteries, loss of a large number of smooth muscle cells in the mid-membrane, thinning of the outer membrane, and luminal occlusion, etc. The large vessels at the base of the skull are usually not involved, and there are no amyloid deposits and no mid-membrane deposits. The specific pathogenesis is still under study.
Symptoms
1. Onset: early age, mostly in 20-40 years old. It is more common in males, with a male to female ratio of 3.2:1. The first symptom is walking disorders and weakness of one side of the lower limbs, or it may be characterized by personality changes, memory disorders and vestibular nerve symptoms. Half of the patients have insidious neurological symptoms, with chronic course and phased aggravation, and the other half of the patients start in the form of stroke, but with normal blood pressure.
2. Encephalopathic symptoms: similar to Binswanger’s disease, the main manifestations are dementia, pyramidal signs, extrapyramidal symptoms and pseudo medullary palsy. The disease starts with amnesia and gradually develops memory disorders, loss of calculation ability, disorientation, personality change and emotional control, and later manifests as speechlessness or immobility, and deafferentation episodes. There is no aphasia, anosognosia, dysarthria, or circadian inversion. Pseudo medullary palsy, asymmetric pyramidal signs on one or both sides, increased muscle tone in more than half of the patients were seen in all patients. A small number of patients showed brainstem symptoms such as oculomotor dyskinesia, vertigo, and nystagmus; a small number of patients showed motor deficits, and a very small number of patients showed mild sensory deficits.
3. Hair loss: most cases may have hair loss, appearing at the age of 10 to 20. It is distributed on the forehead and the top of the head, manifesting as thinning hair or baldness, with normal or mildly reduced sweat hair around the body. Skin keratinization, ulcers, dry skin syndrome and pigmented spots can be seen.
4. Low back pain: most patients have a history of acute low back pain, mostly caused by lumbar disc herniation, and more than half of the patients have degenerative changes of lumbar spine. In some cases, MRI shows disc degeneration and cauda equina compression, and in some cases, spinal cord arachnoid adhesion and suspected neurofibroma can be seen. Thoracolumbar vertebrae migration is a good place for lumbar disc herniation, and it is easy to be obstructed, which suggests that lumbar pain is by no means a single cause. Spinal pathologies such as hunchback and deformational cervical spondylosis can be seen. Dental caries is common, and symptoms such as deformity of both elbows, calcification of the collateral ligaments, and high hard palate are seen.
Examination
1. Cerebrospinal fluid routine examination
Cerebrospinal fluid and serum ApoE polymorphism and Tau protein quantification, β-amyloid fragment, have diagnostic significance.
2. Neuroimaging examination
CT shows diffuse cerebral white matter lesions, cavernous infarcts in the basal nuclei and cerebral white matter.MRI examination, T2-weighted image can see extensive high signal in the cerebral white matter; basal nuclei, cerebral bridges and cerebral peduncles are often seen as small scattered high signals; while digital subtraction angiography (DSA) is not abnormal in more than half of the cases, small arteries with serpentine walls can be seen in the rest of the cases, atherosclerosis of the thick arteries can be seen in some of the cases.SPECT examination Cerebral blood flow can be widely or predominantly reduced in the frontal lobe, and there are no abnormalities in immunity-related indicators such as antinuclear antibodies.
Diagnosis
1. Symptoms appear before 40 years of age, with progressive (sometimes transient pause) mental retardation, pyramidal tract signs, extrapyramidal symptoms, and pseudo medullary palsy, and imaging lesions predominantly in the diffuse subcortical white matter.
2. Baldness or widespread hair thinning at an early age (10-20 years).
3. Acute recurrent low back pain with deformational spondylosis or disc herniation.
4. Blood pressure <140mm/90mmHg without taking antihypertensive drugs.
5. No disease that infringes on the white matter of the brain, such as adrenoleukodystrophy.
If the above 5 items are present, it is a confirmed case; if one of items 2 or 4 is not clear, and the other 4 items are present, it is a probable case; if a sibling of a confirmed case and both parents are married in close relationship, and there is a manifestation of encephalopathy, or if there are items 2 and 3, it is a suspected case.
The following items can be used as diagnostic references: (1) genetic background of consanguineous marriage of both parents or grandparents; (2) stroke or staged progression; (3) diffuse cerebral white matter lesions and lacunar infarcts in the basal nuclei and cerebral white matter on CT/MRI.
Treatment
There is no specific therapy for this disease, and treatment with ticlopidine can stop stroke attacks.
Prognosis
Patients usually die within 10 years of the onset of encephalopathic symptoms and may survive for 10 to 20 years with improved and enhanced medical and nursing care.