Seminars in Cerebrovascular Diseases and Stroke最新文献

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a human genetic disease of small vessels characterized by autosomal dominant transmission, presence of small subcortical strokes, and leukoencephalopathy. Lesions affect mainly the brain, but the vasculopathy occurs in other organs and the diagnosis can be made by skin biopsy. Clinical manifestations include strokes, migraine with aura, depression, vascular dementia, and seizures (10%). Onset is at about age 30 with migraine preceded by aura; recurrent ischemic lacunar strokes begin to occur at age 45, usually in patients without traditional vascular risk factors. Brain MRI shows white matter lesions at 20 years of age, and skin biopsies are also positive at this early age. Poststroke vascular depression usually follows, leading to a pseudobulbar syndrome and to severe subcortical vascular dementia; death occurs at a mean age of 65 years. CADASIL maps to the short arm of chromosome 19. Notch3, the mutated gene, was previously unknown in humans and encodes for a large transmembrane receptor belonging to the Notch/LIN-12 family, involved in cell fate during development. Notch3 expression is highly restricted to the vascular smooth muscle cell. Mutations lead to tissular accumulation of the extracellular domain of the protein. Animal models include the Drosophila lethal-Abruptex and transgenic A90C-Tg-mice; pathological changes similar to those observed in CADASIL are seen in the Tg-mice. There is hope that the animal models would eventually provide a successful treatment for CADASIL patients.

Prevailing definitions of dementia are based on the Alzheimer disease (AD) model, which places major emphasis on memory impairment. In other dementias, such as vascular dementia (VaD), several other cognitive dysfunctions predominate over the memory disorder. The cognitive pattern changes according to the type of VaD. In multi-infarct dementia (MID), cortical lesions may cause loss of instrumental functions manifested by aphasia, amnesia, apraxia, or agnosia. Language in MID patients has shorter phrase length, restricted lexical variability, simplified syntax, and low verbal fluency; dysarthria or mechanical impairment of speech with abnormal pitch, melody, or articulation rate also occur. The latter are rare in degenerative dementias. Compared with AD, patients with MID demonstrate superior performance on verbal learning and memory, better delayed recall, and lower rates of forgetting, intrusions, and false positives. Subcortical ischemic dementia, subcortical hemorrhages, or single subcortical strategic infarcts frequently impair executive functions, attention, and speed of information processing; anterograde memory is generally less impaired than in AD patients. The two main problems of batteries used for evaluation of dementia such as those recommended by CERAD (verbal fluency test, a brief naming test such as the Modified Boston Naming Test, free recall of a word list, with immediate and delayed recall, followed by a recognition task of the same words, and line drawings of figures), as well as the Mini-Mental State Examination (MMSE), are (1) their strong emphasis on memory, temporal and spatial orientation, calculation, language, and constructional praxis, and (2) their failure to assess executive functions. Simple tests of executive function include the Trail Making Test, the Wisconsin Card Sorting Test, and the EXIT-25. A simple and effective test is the CLOX, an executive variation of the clock-drawing task. Depressive symptoms and other psychiatric disturbances are particularly common in VaD and become sources of cognitive and functional disability. Several questionnaires assess the neuropsychiatric manifestations of dementia including the Neuro-Psychiatric Inventory (NPI), the BEHAVE-AD test, the Cohen-Mansfield Scale, and the CERAD Behavioral Rating Scale for Dementia. Finally, development of dementia after a stroke may represent true VaD in patients with intact cognition before the stroke, or AD + CVD when the dementia occurs in patients that already had memory problems before the ictus. The diagnosis of VaD is a challenging clinical problem that encompasses the fields of medicine, neurology, psychiatry, and psychology.

Dolichoectatic basilar artery has become a more frequent finding in patients examined with modern neuroimaging techniques. Described complications of basilar dolichoectasia include ischemic infarcts of the brainstem, compression of cranial nerves, and hydrocephalus. We describe a patient who initially presented with pontine ischemic infarct related to dolichoectatic basilar artery. Within several days of her admission, the patient died. Her basilar lesion ruptured, resulting in a devastating subarachnoid hemorrhage, a relatively rare and fatal complication of this condition. We postulate that any deterioration in a patient with dolichoectatic basilar artery should not be automatically attributed to infarct, and that hemorrhage should be considered too.

Color doppler imaging (CDI) is a diagnostic tool that allows non-invasive evaluation of the orbital and intra-cranial structures. It operates by the doppler principle, which is detecting changes in the frequency of sound that is reflected from flowing blood, allowing estimation of flow velocity. CDI has been used in the diagnosis and follow up of ophthalmic conditions such as central retinal artery occlusion, central retinal vein occlusion, arteritic and non-arteritic ischemic optic neuropathy and the ocular ischemic syndrome. In addition, orbital conditions like varices can be evaluated. Transcranial doppler has been used to assess strokes and arteriovascular malformations of the brain. The main limitation of CDI is that it provides information about velocity and not flow. Despite this, it remains a valuable tool to diagnose ocular and intracranial conditions characterized by ischemia or abnormal blood flow.

Dolichoectasia, or the dilation and increased curvature of intracranial vessels, has long been linked to atherosclerosis. Rather than the result of atheromatous alterations of the vessel wall, investigators now believe that the primary lesion is a defect in the internal elastic lamina and the elastic components of the media. Remodeled by shear and stress related to blood flow and turbulence, the thickened intima and lipid deposits are secondary phenomena. In some patients, dissection of the intracerebral vessel wall may be the initial event, and with the passage of time, dolichoectasia may be the final phase. We present two patients to illustrate the spectrum of changes that can involve the posterior circulation. The first patient had dolichoectasia of the basilar artery, and the second patient had dissection of the vertebral artery. Each patient died from diffuse subarachnoid hemorrhage, and each had a postmortem examination. To better understand the genetic mechanisms leading to smooth muscle and elastic fiber defects in dolichoectasia, we can focus on a subgroup of patients with polycystic kidney disease. This cohort of renal patients has an abnormally high frequency of intracranial aneurysms, hemorrhages, and dolichoectasia of intracranial vessels. Polycystin is the protein product of the gene PKD1, which undergoes mutation in autosomal dominant polycystic kidney disease. By studying the relationship between aberrant polycystin expression and vascular phenotype, we may someday understand the vascular abnormalities at the molecular level.

Migraine headache has been associated with an increased frequency of certain cardiac structural abnormalities including patent foramen ovale (PFO) and right-to-left shunts. Improvement or resolution of migrainous symptoms has been reported after procedures performed to close PFO or atrial septal defects. Some authors advocate prospectively evaluating the use of interventional modalities in the treatment of migraine headache. The relevant epidemiology, diagnostic techniques, and treatment options for PFO and associated atrial septal abnormalities are presented initially. A systematic review of the investigations demonstrating an association between these entities and migraine headache is followed by a critical review of the studies noting improvement in migraine symptoms after PFO closure. Reports suggesting the possible utility of percutaneous closure procedures in the treatment of migraine headache are largely retrospective and uncontrolled. Prior to advocating prospective trials to further study the role of invasive procedures in the treatment of migraine, the benign nature of the disorder and the possibility of procedural complications should be carefully considered.