Focal Cerebral Arteriopathy in Young Adult Patients With Stroke.

Background and Purpose- Focal cerebral arteriopathy is monophasic inflammatory stenosis of the distal internal carotid artery or the proximal segment of the middle cerebral artery. It is one of the most common causes of acute arterial ischemic stroke in young children but is a less familiar entity for adult neurologists. Methods- We retrospectively reviewed stroke service radiology records at a tertiary referral center from January 2013 to December 2014. Focal cerebral arteriopathy was defined as nonprogressive unifocal and unilateral stenosis/irregularity of the distal internal carotid artery or its proximal branches. Only patients aged 16 to 55 years with stroke were included. Results- There were 5 cases of focal cerebral arteriopathy: 2 males and 3 females. Three cases were from the cohort of 123 acute presentations of young stroke, and 2 cases were outpatient referrals. The mean age (range) was 43 (32-55) years. The majority presented with recurrent transient ischemic attacks/minor strokes within a single vascular territory over days to weeks. All cases had characteristic radiological features. Interval imaging demonstrated resolution in 1 case and improvement in 3 cases. Functional outcome was excellent with discharge modified Rankin Scale score ranging from 0 to 1. Recurrence occurred in 1 case. Conclusions- Focal cerebral arteriopathy is a rare cause of arterial ischemic stroke in young adults. Follow-up intracranial imaging is essential to differentiate from progressive arteriopathies. Evidence-based treatment warrants further investigation. Prognosis is favorable.

Complement activation associates with saccular cerebral artery aneurysm wall degeneration and rupture.

OBJECTIVE: Saccular cerebral artery aneurysm (SCAA) wall degeneration and inflammatory cell infiltrations associate with aneurysm rupture and subarachnoid hemorrhage, resulting in a devastating form of stroke. The complement system is the key mediator of inflammation and household processing of injured tissue. We studied how complement activation associates with SCAA wall degeneration and rupture to better understand the pathobiology of SCAA wall rupture. METHODS: Unruptured (n = 26) and ruptured (n = 32) SCAA fundi resected after microsurgical clipping were studied by immunostaining for complement activation (membrane attack complex [MAC]) and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling reaction for related cell death. Complement activation was correlated with clinical and other histological parameters. Electromicroscopy and immunoelectron microscopy were used for locating MAC depositions at the ultrastructural level. RESULTS: MAC localized consistently in a decellularized layer in the outer SCAA wall, and was found in all SCAA samples. The percentage of MAC-positive area relative to the total SCAA wall surface area (range, 5-77%) was greater in ruptured (n = 25; median, 39%) than in unruptured SCAAs (n = 18; median, 20%; P = 0.005). It also associated significantly with SCAA wall degeneration (P < 0.001), de-endothelialization(P < 0.001), and CD163+ macrophage (P = 0.023) and T-lymphocyte (P = 0.030) infiltrations. Apoptotic terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling-positive nuclei and MAC were located at the same wall areas in four out of 14 double-stained samples, but no double-positive cells were found. Electromicroscopy and immunoelectron microscopy of an unruptured SCAA showed cell death in the MAC-positive layers in the outer SCAA wall. CONCLUSION: These data suggests that complement activation and MAC formation are involved in SCAA wall degeneration and rupture.

Differences between arterial occlusive and cortical photothrombosis stroke models with magnetic resonance imaging and microtubule-associated protein-2 immunoreactivity.

The differences between two models of cerebral ischemia [middle cerebral arterial transection (MCAT) and cortical photothrombosis (PT)] were explored with multiparametric MRI of apparent diffusion coefficient trace (ADCtr), cerebral blood flow (CBF) and T1. Microtubule-associated protein-2 (MAP2) immunoreactivity sections aligned with the MR images in the same coronal plane were used to map the infarct and to guide region-of-interest selection. In ischemic cortex, the larger T1 increase in PT versus MCAT (42+/-7% vs. 16+/-5%) is related to the different character of edema between these models; yet, neither CBF nor ADCtr discriminated between them at 3.5 h, suggesting that different mechanisms of ischemic damage to the brain cells resulted in the same ADCtr value. CBF and ADCtr were depressed in immediately adjacent ischemic border by 27+/-7% and 47+/-10%, respectively, in MCAT but not in PT, suggesting marginal perfusion in MCAT. CBF in homotopic normal cortex in the opposite hemisphere was higher for PT compared with MCAT (199+/-20 and 134+/-10 ml/100 g/min, respectively). Different pathological processes in the two models affect CBF, ADCtr and T1 in a unique, regionally specific manner. The PT model differs substantially from the MCAT and is not a model of cortical ischemia with an appreciable border zone.

Clinicopathological and genetic studies of two further Italian families with cerebral autosomal dominant arteriopathy.

We report on two Italian families with an early-adult onset autosomal dominant disorder, characterized by leukoencephalopathy, migraine, psychiatric disturbances, stroke and dementia. These findings fulfill the diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) syndrome. Moreover, to confirm the CADASIL gene location to 19p12, we performed a linkage analysis with four microsatellite markers. The results of the genetic study gave positive but not significant lod scores, indicating only weak evidence of a linkage with 19p12. In one autopsy case, we found extensive ischemic changes due to the selective involvement of the small muscular arteries of the cerebral white matter. The lesions consisted of a thickening of the media with deposition of granular eosinophilic material. Ultrastructural examination of the arterial walls showed graded damage to smooth muscle cells, mostly of the longitudinal layer, and an abnormal proliferation of basal lamina components. Immunocytochemical analysis showed strong reactivity using antibodies to collagen IV and smooth myosin proteins. The results suggest a primary involvement of the smooth muscle cells of small cerebral arteries, with a secondary alteration of basal lamina components and elastic tissue.

[Isolated angiitis of the central nervous system with high immune complex titer, first presenting as intracranial hemorrhage during cesarean section].

A case of isolated angiitis of the central nervous system (IACNS) which first presented as intracranial hemorrhage during cesarean section was reported. The patient was a 27-year-old female who showed severe headache during cesarean section. CT scan disclosed hematoma in the right parieto-occipital area. Carotid and vertebral angiograms demonstrated striking areas of stenosis and irregularity of all intracranial arteries. There was no abnormality in the branches of the external carotid arteries. Systemic angiograms showed no evidence of systemic vasculitis. Biopsy of the temporal artery showed no abnormal findings. Titer of immune complex was elevated. Angiitis showed no improvement with corticosteroid alone, but improved markedly with corticosteroid plus cyclophosphamide. Elevated titer of immune complex became normal. Treatment with a combination of corticosteroid and cyclophosphamide is recommended in IACN.

Hemorrhagic stroke due to cerebral vasculitis and the role of immunosuppressive therapy.

Cerebral vasculitis may occur in isolation or in conjunction with a systemic illness. Although a relatively infrequent cause of intracerebral or subarachnoid hemorrhage, it should be considered in a setting of relevant systemic symptoms, an unexplained progressive neurologic disorder, or in a patient lacking risk factors for hemorrhagic stroke. Diagnosis may be difficult because the results of most studies may be normal or nonspecific. Because treatment is effective in many of the cerebral vasculitides, vigorous pursuit of the diagnosis is warranted.

[Intracranial arteritis with circulating immune complexes]. / Intrakranielle Arteriitis bei zirkulierenden Immunkomplexen (ZIK).

Thirty-eight patients below the age of 50 years were investigated and in twelve, circulating immune complexes were found. Eight of these had angiographic evidence of an arteritis of the intracranial vessels. The causative factors, the role of the circulating immune complexes and the angiographic appearances in intracranial arteritis are discussed.

[Giant cell thromboangiitis in a patient taking an oral contraceptive (author's transl)]. / Thromboangéite à cellules géantes au cours d'une contraception orale. Etude anatomo-clinique et immunologique.

Pathological examination in a patient who developed an ischemic cerebrovascular accident while taking an oral contraceptive demonstrated widespread lesions in the right and left carotid regions. Histological examination revealed the presence of an obliterating thromboangiitis in the arterial walls, with subendothelial fibrosis of the intima, arterial thrombosis, and a marked giant cell reaction where the lesions were in contact with the internal elastic layer. Immunological and biological anomalies confirmed the inflammatory nature of the lesion with the presence of anti-ethinyl estradiol antibodies in the serum and circulating blood immune complexes. These biological and histological results suggest the immunological nature of the mechanism of origin of the cerebrovascular accident in this case.

PIP: The article presents the case of a 28-year-old patient, on oral contraception for 2 years, who suddenly developed massive right hemiplagia. Pathological observations revealed widespread lesions in the right and left carotid regions, while histological observations revealed the presence of obliterating in the arterial walls, causing arterial thrombosis and giat cell reaction where the lesions were in contact with the internal elastic layer. Antiethinyl estradiol antibodies were found in the serum, together with immune circulating complexes. Such results suggest the immunological nature of the case presented.