[Primary vasculitis of internal carotid and vertebral arteries: a role of cytokines, transforming growth factor beta 1 and basic fibroblast growth factor]. / Pervichnyi vaskulit vnutrennei sonnoi i pozvonochnoi arterii: rol' tsitokinov, transformiruyushchego faktora rosta ß1 i osnovnogo faktora rosta fibroblastov.

OBJECTIVE: To study clinical/laboratory signs of primary vasculitis (PV) of the internal carotid artery (ICA) and vertebral artery (VA). MATERIAL AND METHODS: We examined 31 patients (23 men, 74%, mean age - 36.2±5.7 years) with ICA/VA PV verified by vessel wall contrast enhancement on black blood MRI (T1-weighted fat and blood suppressed sequences with- and without contrast injection) at the Research Center of Neurology (Moscow) from January 2012 to September 2019. Systemic vasculitis was excluded in all cases. Interleukins (IL-1ß, IL-2, IL-6, IL-17), TNF-a, transforming growth factor beta 1 (TGF-ß1) and basic fibroblast growth factor (bFGF) were analyzed by ELISA in 25 patients. Control group consisted of 21 healthy volunteers (12 men, 57%; mean age - 35.3±10.2 years). RESULTS: Clinical manifestations of ICA/VA PV included: ischemic stroke (IS) (94%), which combined with transient ischemic attacks (TIA) in 35%; isolated TIA (3%); Tolosa-Hunt syndrome (3%). Recurrent strokes were observed in 41% of patients on average in 5.3±2.1 months. Carotid artery was involved in 77%, VA - in 16%, both arteries - in 7%. Concomitant involvement of ICA/VA branches was in 19% patients. The level of arterial damage was follows: Intracranial part of arteries involved in 55%, intra-extracranial - in 35%, extracranial - in 10%. Bilateral involvement was found in 26%. Headache/neck pain in the acute IS period was observed in 21%. IS severity (NIHSS) was as follows: moderate (59%), mild (34%), moderately severe (7%). Disability after 3 months according to mRankin scale was as follows: mild (72%) moderate (21%), none (7%). The laboratory study revealed an increased levels of IL-6 (8.19±3.89 pg/ml vs 4.7±1.48 in control, p=0.000), IL-2 (5.64±1.82 pg/ml vs 4.30±1.65, p=0.013), TNF-a (36.9±33.66 pg/ml vs 12.68±5.93, p=0.000), TGF ß1 (2.77±1.60 pg/ml vs 1.63±0.64, p=0.006) and bFGF (417.67±132.68 pg/ml vs 335.71±105.08, p=0.018). The levels of IL-1ß and IL-17 did not differ significantly from the control. CONCLUSION: ICA/VA PV has a number of clinical peculiarities. Proinflammatory cytokines produced by Th17 and Th1 CD4+ lymphocytes as well as bFGF and TGR-ß1 play a role in its pathogenesis. Normal levels of IL-1ß and IL-17 suggest that they are not significant in the development of isolated inflammation in ICA/PA, in contrast to systemic inflammation in giant cell arteritis, in which, according to literature data, their level increases. Isolated ICA/PA inflammation seems to be caused by transaxonal (trigeminal nerve, upper-cervical roots, autonomic nerves) spread of pathogens that initiate immune inflammation in the ICA/PA wall.

[Intracerebral hemorrhage in the late period of internal carotid artery dissection]. / Vnutrimozgovye krovoizliianiia v pozdnem periode dissektsii vnutrennei sonnoi arterii.

Cervical artery dissection is the common cause of ischemic stroke in young and middle-age patients. According to our previous studies, dissection is related to arterial wall dysplastic changes, which in their turn are due to mitochondrial cytopathy. The authors describe three male patients who at the age of 53, 25 and 35 years underwent internal artery (ICA) dissection with occlusion of its lumen and subsequent recanalization in one of them. In 3.5 months, 13.5 years and 3 years respectively, patients developed intracerebral hemorrhage (IСH), which was not related to arterial hypertension, cerebral arterial aneurysms and anticoagulants. IСH were located on the side of ICA occluded after dissection (2 patients) or bilaterally in the territory of patent ICA (1 patient). Multivoxel 1H-MR spectroscopy performed in one patient on 40 and 48 days after ICH revealed a high lactate peak in the externally unchanged hemispheric white matter. It is assumed that mitochondrial cytopathy in patients with dissection may involve large as well as small intracerebral arteries (mitochondrial microangiopathy), which could be the cause of ICH.

[Primary central nervous system vasculitis]. / Pervichnyi vaskulit tsentral'noi nervnoi sistemy.

Primary vasculitis (angiitis) of the central nervous system (PACNS) is a rare disease targeting the vessels of the brain, spinal cord and leptomeninges without systemic involvement. The etiology is not clear enough. The authors review clinical, laboratory and radiological features of PACNS. Clinical manifestations are variable and depend on the caliber of affected vessels. The main clinical manifestations of small sized vessel vasculitis include encephalopathy (cognitive disorders, epileptic seizures), headache and transient cerebral ischemia. The main clinical presentation of vasculitis of medium/large cerebral arteries is ischemic strokes, which usually develop in different vascular territories. CSF findings in the majority of patients show modest lymphocytic pleocytosis, elevated protein level and occasionally the presence of oligoclonal bands. MRI data are not specific and include infarcts, hyperintensity (FLAIR) and sometimes tumor-like lesions. The gold standard for the verification of PACNS affected small-sized arteries is brain and leptomeningeal biopsy. Cerebral angiography allows the verification of vasculitis of medium and large cerebral arteries revealing segmental narrowings (beading). High resolution black blood MRI before and after contrast injection may visualize intracranial vessel wall contrast enhancement - the sign of inflammation in intracranial arteries. Treatment of PACNS includes corticosteroids and cyclophosphamide. In the case of patient intolerance, rituximab and blockers of tumor necrosis factor may be used.