Acquired Hemicerebral Atrophy Secondary to Chronic Internal Carotid Steno-Occlusive Disease: A Case Series

Abstract

Cerebral atrophy is a common finding in elderly patients; however, cerebrovascular disease causing progressive focal cerebral atrophy and dysfunction is unusual. In this report, we present 3 cases of hemicerebral atrophy due to ipsilateral internal carotid artery (ICA) stenosis or occlusion mimicking neurodegenerative conditions. Patient 1 had a frontal dysexecutive syndrome potentially consistent with a diagnosis of behavioral variant frontotemporal dementia; however, neuroimaging revealed a chronically occluded left ICA and a pattern of atrophy restricted to the left middle cerebral artery territory, suggestive of a vascular etiology. Patient 2 presented with progressively worsening seizures and right-sided weakness consistent with left hemispheric dysfunction, with radiographic evidence of left hemicerebral atrophy. Angiography revealed a chronic dissection of the left ICA leading to left cerebral hypoperfusion. Patient 3 had asymmetric parkinsonism, alien limb, and cognitive impairment consistent with a diagnosis of corticobasal syndrome. His imaging, however, revealed atrophy and encephalomalacia within the anterior circulation watershed territories with chronic, severe stenosis of the left ICA suggestive of a chronic hypoperfused state. In this case series, we report 3 examples of hemicerebral atrophy secondary to chronic ipsilateral ICA vascular disease with diverse progressive clinical symptoms mimicking primary neurodegenerative conditions. This case series highlights the importance of considering chronic hypoperfusion and large-vessel severe stenosis or occlusion in patients with cognitive impairment and evidence of asymmetric brain atrophy. In addition to symptomatic treatment, the management of vascular risk factors including treatment with antiplatelet agents, statins, and revascularization procedures can be considered.

Introduction

Cerebral atrophy is common in the aging population and is influenced by a variety of factors including sex, vascular disease, and underlying neurodegenerative conditions.¹ With the development of advanced imaging techniques, certain patterns of atrophy are used to predict underlying neuropathologic conditions and correlate with neurologic deficits or impairment of specific cognitive domains.^2,3 Cerebrovascular disease is a strong risk factor for cognitive impairment and can lead to both cortical and subcortical atrophy.⁴ Although the symptoms of cerebrovascular disease often present acutely, as in ischemic stroke, long-standing regional hypoperfusion can cause slow progression of symptoms and are associated with focal areas of atrophy. In this series, we present 3 cases of hemicerebral atrophy due to ipsilateral carotid artery steno-occlusive disease mimicking neurodegenerative conditions.

Case 1

An 81-year-old right-handed Korean woman with history of breast cancer in remission following partial mastectomy, chemotherapy, and radiation presented to neurology clinic for evaluation of cognitive impairment.

Four years prior to presentation, her family noted changes in personality and behavior with increased irritability, decreased personal hygiene, and hoarding. She later developed difficulty preparing meals or dressing herself, and her language deteriorated to the extent she would only speak in simple sentences and had trouble with naming objects. Her right hand also became progressively uncoordinated, rendering her unable to handwrite or hold utensils while eating.

Her neurologic examination was notable for mild right hemiparesis, spasticity, and hyperreflexia. Neglect and ideomotor apraxia were not present. Cognitive evaluation revealed intact visuospatial processing and verbal and visual memory, but there were significant deficits in attention, language, and executive functioning consistent with a frontal dysexecutive syndrome. Magnetic resonance imaging (MRI) of the brain revealed asymmetric atrophy of the left frontal, temporal, and parietal lobes without significant gliosis or encephalomalacia (Figure 1A and B). Magnetic resonance angiography (MRA) and computed topography angiography demonstrated complete occlusion of the left internal carotid artery (ICA) from the skull base to the level of the supraclinoid segment with minimal collateral flow across the anterior communicating artery (ACOM) to the left anterior cerebral artery (ACA) and middle cerebral artery (MCA; Figure 1C and D). Taken together, these findings were suggestive of chronic hypoperfusion within the left anterior circulation leading to cortical atrophy, and the patient was started on aspirin and a statin for secondary prevention.

Figure 1.

A, Axial and B, Coronal Fluid Attenuated Inversion Recovery (FLAIR) sequences on magnetic resonance imaging (MRI) demonstrating prominent atrophy within the left middle cerebral artery (MCA) territory without associated T2 signal changes. C, Magnetic resonance angiography (MRA) showing absent flow within the left intracranial internal carotid artery and left MCA. D, Computerized tomography angiography (CTA) demonstrating minimal flow within the left MCA.

Case 2

A 41-year-old right-handed African American woman with a history of epilepsy and hypertension was admitted to the inpatient neurology service after presenting with increased seizure frequency and intermittent right hemiparesis, sensory loss, and dysarthria.

On admission, the patient’s examination was notable for mild aphasia and dysarthria, mild right hemiparesis and sensory loss, and right-sided spasticity. Continuous electroencephalography no further seizures or epileptiform discharges, and she was started on levetiracetam. A brain MRI revealed areas of T2 prolongation throughout the left MCA territory with associated atrophy (Figure 2A).

Figure 2.

A, Magnetic resonance imaging (MRI) Fluid Attenuated Inversion Recovery (FLAIR) images demonstrating T2 signal prolongation and atrophy within left middle cerebral artery (MCA) territories. B, Magnetic resonance angiography (MRA) with absent flow in the left MCA.

An MRA revealed incomplete opacification of the left ICA distal to the carotid bifurcation, with minimal flow extending into the cavernous ICA, left ACA, and first segment of the left MCA (Figure 2B). Digital subtraction angiography confirmed high-grade stenosis of the extracranial left ICA with filling of the left anterior circulation through collateralization with the left external carotid, left posterior communicating artery, and ACOM. Given her age and few other vascular risk factors, these findings were most consistent with chronic dissection leading to hypoperfusion of the left anterior circulation. She was initially treated with aspirin and a statin for secondary prevention. Her aphasia and sensorimotor deficits gradually worsened over 2 years of follow-up. Magnetic resonance perfusion with acetazolamide challenge revealed a 5- to 6-second delay in left anterior circulation peak perfusion compared to the right and no augmentation or steal following acetazolamide, and she ultimately underwent revascularization with a left pial synangiosis. Since her revascularization procedure, the patient has continued to have stable aphasia and right hemiparesis with several interval MRI scans demonstrating no new areas of restricted diffusion or progression of encephalomalacia.

Case 3

An 81-year-old man with history of diabetes, hypercholesterolemia, and hypertension presented to neurology with 2 years of abnormal gait and cognition. He had increasing difficulty with reading and writing and could no longer complete crossword puzzles. He also experienced slowness and shuffling of gait which resulted in multiple falls. A trial of carbidopa–levodopa resulted in mild subjective gait improvement. Several months later, the patient noticed that his left arm tended to lift nonpurposefully.

On examination, the patient had marked cognitive impairment involving multiple domains (Montreal Cognitive Assessment of 5/30), a prominent grasp reflex, and multiple right parietal signs including left-sided neglect, astereognosis, atopognosia, and ideomotor apraxia. He also had severe left-sided bradykinesia and rigidity with dystonic posturing and mild left-sided alien limb phenomenon. The patient was able to stand with assistance from his wheelchair but had a short and shuffling stride length with dystonic foot inversion and plantar flexion of the left foot.

His workup included an MRI that revealed chronic right MCA territory infarcts with surrounding encephalomalacia and atrophy (Figure 3), and MRA revealed severe right ICA stenosis consistent with a chronic dissection. He was started on aspirin and a statin for secondary stroke prevention, carbidopa–levodopa for parkinsonism in the setting of corticobasal syndrome (CBS), and botulinum toxin injections for left hemidystonia.

Figure 3.

Magnetic resonance imaging (MRI) Fluid Attenuated Inversion Recovery (FLAIR) images demonstrating T2 signal prolongation and atrophy within the right middle cerebral artery (MCA) and right anterior cerebral artery (ACA) distributions.

Discussion

Cerebral atrophy is a well-documented consequence of vascular disease and often occurs following an acute stroke with associated gliosis and encephalomalacia. Slowly progressive and chronic forms of atrophy can also arise in the absence of an overt stroke episode and are mediated through either recurrent microthromboembolic events or prolonged hypoperfusion.^1,5 As opposed to infarction, hypoperfused tissue maintains a marginally adequate cerebral blood flow (CBF) above the ischemic threshold thereby avoiding cell death from sudden energy failure or rapid neuronal excitotoxicity.⁶ Chronic reductions in cerebral perfusion may progressively impair cellular metabolism and protein synthesis thereby leading to delayed neuronal death.^6,7 In the setting of long-standing focal arterial narrowing, cellular injury is restricted to the area of reduced perfusion and may result in a focal atrophy pattern.⁷

In this case series, we report 3 examples of chronic hemicerebral atrophy secondary to ipsilateral ICA steno-occlusive disease with diverse clinical and radiographic features mimicking primary neurodegenerative conditions or other hemicerebral diseases. The patient in case 1 had clinical features of a frontal dysexecutive syndrome with evidence of left frontal and temporal lobe atrophy potentially consistent with a diagnosis of behavioral variant frontotemporal dementia.⁸ However, neuroimaging revealed a chronically occluded left ICA that directly correlated with isolated atrophy in the left MCA territory, strikingly sparing the ACA and PCA territories, consistent with a vascular etiology. In case 2, the patient presented with progressively worsening seizures and right-sided weakness consistent with left hemispheric dysfunction with reduced diffusion and T2 prolongation within the left frontal, parietal, and temporal lobes and evidence of left hemicerebral atrophy potentially suggestive of Rasmussen encephalitis; however, angiography revealed a chronic stenosis of the left ICA leading to hypoperfusion throughout the left anterior circulation. Already in a hypoperfused state, seizures may have led to increased metabolic demand resulting in focal ischemia and further cortical atrophy.⁹ Finally, the patient in case 3 demonstrated asymmetric parkinsonism, alien limb, and cognitive impairment consistent with a diagnosis of CBS.¹⁰ His imaging, however, revealed atrophy and encephalomalacia within the right MCA/ACA watershed territories with severe stenosis of the left ICA suggestive of a chronic hypoperfused state. Although previously thought to be synonymous with a histopathologic diagnosis of corticobasal degeneration, autopsy studies have demonstrated CBS can occur due to various neurodegenerative pathologies such as amyloid-β plaque with neurofibrillary tangles, tauopathy, and synucleinopathy.¹⁰ Corticobasal syndrome secondary to cerebrovascular disease is much less common and only reported in a few case reports in patients with ipsilateral ICA occlusions or following carotid endarterectomy.^11-13

The precise mechanisms underlying cerebral atrophy related to chronic hypoperfusion are still incompletely understood; however, by using positron emission tomography, Yamauchi and colleagues demonstrated evidence of increased oxygen extraction, termed misery perfusion, in tissues supplied by a stenotic carotid artery.¹⁴ This response serves as an early compensatory response to decreased CBF but over time is highly predictive of focal atrophy. Such hypoperfused tissue remains above the ischemic threshold due to maximal vasodilation at the limit of the autoregulatory curve and extracts oxygen at the utmost capacity. In this highly vulnerable state, even minor changes in local tissue perfusion may disrupt cellular processes and contribute to selective dendritic and cortical neuronal injury.⁵ The consequences of such atrophy were demonstrated in the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study, where hemodynamic-related cerebral atrophy was identified as a strong predictor of cognitive impairment, particularly involving executive functioning.¹⁵ The impact on cognitive function was further magnified when combined with evidence of ischemic white matter lesions suggesting a synergistic relationship in disrupting neural networks. Despite the apparent relationship between severe steno-occlusive disease and cognitive impairment, prospective studies of carotid revascularization have not demonstrated any impact on cognitive performance measures.¹⁶ The currently enrolling Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial-2 is evaluating cognitive function as a secondary end point and may shed more insight on the impact of such procedures.¹⁷

This case series highlights the importance of considering chronic hypoperfusion and large vessel stenosis in patients presenting with clinical syndromes consistent with a neurodegenerative process. Such patients require structural neuroimaging to evaluate for lesions that may result in cognitive impairment and vascular imaging should be considered in those with evidence of asymmetric cerebral atrophy, particularly if it conforms to a vascular territory. Currently, there is lack of high-quality evidence to guide treatment for such patients; however, aggressive medical management of vascular risk factors, including antiplatelet agents and high-intensity statin, is warranted. Further studies are necessary regarding the possible benefit of therapeutic interventions for such patients including revascularization procedures. A waiver of informed consent was granted by the local institutional review board.