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Objective: To evaluate transforming growth factor beta (TGF-β) in patients with cervical artery dissection (CeAD)., Material and Methods: TGF-β was studied by enzyme immunoassay in 74 of 336 patients with CeAD observed at the Research Center of Neurology (Moscow) from 2000 to 2021. The average patient's age at the time of TGF-β study was 41.6±9.8 years; the proportion of women was 51%. TGF-β was studied in the first month of the disease ( n =9), for 2-3 months ( n =12) and at a later period (mean - 4.3±5.03 years) ( n =53). The control group consisted of 20 healthy volunteers, matched for age and sex. Dissection occurred in internal carotid artery (ICA) ( n =42), vertebral artery (VA) ( n =29), ICA+VA ( n =3) and involved 1 artery ( n =58) or 2-3 arteries ( n =16). Clinical manifestations included ischemic stroke (IS) ( n =49), isolated cervical-cephalic headache ( n =23), lower cranial nerve palsy ( n =2). Pathological CeAD tortuosity was detected by angiography in 13 patients, and a dissecting aneurysm in 15 patients., Results: TGF-β1 and TGF-β2 were elevated in patients with CeAD patients compared with the control: TGF-β1 - 4990 [3950; 7900] pg/ml vs. 3645 [3230; 4250] pg/ml, p =0.001; TGF-β2 - 6120 [4680; 7900] pg/ml vs. 3155 [2605; 4605] pg/ml, p =0.001. The highest TGF-β1 and TGF-β2 levels were noted at 2-3 months of the disease. There was no correlation between the TGF-β level and various clinical and angiographic parameters., Conclusion: Increased TGF-β level confirms that CeAD patients have connective tissue disorder that underlies the arterial wall weakness. A higher TGF-β level at 2-3 months of CeAD seems to be connected with an active reparative process in arterial wall after dissection. TGF-β can be used as a biomarker of connective tissue dysplasia in patients with CeAD.

Objective: To study the frequency, angiographic and clinical features of aneurysms and tortuosity (T) in patients with internal carotid artery (ICA) and vertebral artery (VA) dissection., Material and Methods: Three hundred and twenty-seven patients (average age - 37.8±9.1 years, women - 57%) with ICA/VA dissection verified by neuroimaging were studied. Repeated neuroimaging in 2.4±3.3 years was performed in 254 patients. In one case, tortuous ICA fragment resected at the surgery complicated by dissection was histologically studied., Results: ICA/VA aneurysms were found in 46 (14%) patients. At repeated neuroimaging aneurysms did not change (38%), increased (11%) or decreased in size (8%), were not detected (38%) or were detected for the first time (5%). Patients with aneurysms compared with those without aneurysms more often had multiple dissections (44% vs. 20%, p =0.001) and T (35% vs. 13%, p =0.001), but less frequently the artery lumen occlusion in the acute period (15% vs. 40%, p =0.001). T was found in 53 (16%) patients. Patients with T compared with patients without T were older (40.6±8.1 vs. 37.3±9.3 years, p =0.039), more often had aneurysms (30% vs. 11%, p =0.001) and recanalization of occlusion observed in the acute period (89% vs. 54%, p =0.006). Dissection more often occurred in tortuous than in non-tortuous artery (79% vs 21%, p =0.001). During 4.8±3.6 years of follow-up, TIA developed inone patient (2%) with an aneurysm. Histological examination of tortuous ICA fragment, which also contained a small aneurysm, revealed dysplastic changes., Conclusion: The association between aneurism and T in patients with ICA/VA dissection suggests their common basis - the arterial wall weakness due to dysplasia. Age-related changes are also important for T development. T is a risk factor for ICA/VA dissection. Aneurysms formed after ICA/VA dissection have a benign course.

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-1β, IL-2, IL-6, IL-17), TNF-a, transforming growth factor beta 1 (TGF-β1) 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 β1 (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-1β 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-β1 play a role in its pathogenesis. Normal levels of IL-1β 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.

Cervical artery dissection (CeAD) due to arterial wall weakness (dysplasia) is one of the most common causes of ischemic stroke (IS) at a young age. A rare and little known cause of CeAD is Turner's syndrome (TS)-is an inherited disease caused by completely or partially missing X chromosome. In this paper, we describe 2 female patients, aged 27 and 33 years, with genetically confirmed TS (karyotype 45X0) and internal carotid artery dissection(ICAD).TS frequency among our 304 patients with CeAD was 0.07%. Both patients had short stature, received hormone replacement therapy from the age of 14 and had arterial hypertension. In addition, the first patient suffered from hypothyroidism, osteoporosis and survived a nephrectomy for hydronephrosis. ICAD in first patient manifested by IS. MRI of the neck arteries, MRA and CTA revealed intramural hematoma, hemodynamically significant stenosis, which regressed in 4 months. In the second patient, dissection was manifested by local symptoms (Horner's syndrome, cervicocephalic pain on the dissection side). MRA and CTA revealed a precranial dissected aneurysm of the left ICA (on the side of local symptoms), fusiform expansion of the right ICA, and pathological tortuosity of both ICA. The paper discusses the cause of vasculopathy in TS. It is assumed that connective tissue damage is associated with a deficiency of biglycan - extracellular matrix protein, which interacts with collagen and elastin to strengthen the arterial wall. Biglycan gene is linked to X-chromosome which is completely or partlially missing in TS resulting in a biglycan deficiency. The role of sex hormone deficiency as a cause of arterial wall weakness is unlikely.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disease of the central nervous system, mainly affecting the brain stem, cerebellum and spinal cord. The clinical picture includes gradually developing ataxia, double vision, dysarthria, pyramidal and cognitive impairment. Morphological examination reveals T-cell perivascular lymphocytic infiltration with CD4 lymphocytes predominance over CD8 lymphocytes. The cause of the disease is unknown. The article describes two patients (a 18-year-old woman and a 40-year-old man) with typical clinical and MRI manifestations of CLIPPERS, which was confirmed by brain biopsy in the female patient. The duration of follow-up was 3 and 7 years, respectively. Both patients survived an infection 2-3 weeks before the onset of disease that allows one to discuss its role in CLIPPERS pathogenesis. Both patients had a clear clinical and MRI responsiveness to steroids. In the female patient, steroids were replaced by intramuscular administration of the TNF-α blocker adalimumab. During 1,5 years of its use, there were no clinical relapses and pathological brain changes on MRI.

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 1 H-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.

The authors present a clinical-morphological observation of the 47-year old man with a severe fatal ischemic stroke due to middle cerebral artery thrombosis which developed at the site of intimal rupture. The cause of intimal rupture was the arterial wall dysplastic changes. There were no signs of atherosclerosis and hypercoagulation. As the intima rupture did not lead to blood input into arterial wall, but was accompanied by superimposed thrombosis, we suggested to denote such cases as incomplete dissection.

Authors describe a 7-year-old boy, who developed a severe right-sided hemiparesis, aphasia, seizure, and confusion state during sport games. There was no headache. Allergic dermatitis in the past medical history and influenza vaccination 2 weeks before stroke were recorded. On the 12th day of disease, MRI of the brain revealed an acute infarction in the territory of left anterior and middle cerebral arteries with hemorrhagic transformation. MPA (15 day) showed occlusion of the left ACA and MCA. HR-MRI T1_db_fs weighted imaging (36 day) found intramural hematoma (IMH) in ACA and MCA with marked stenosis of the lumen. After 3 months, HR-MRI/MRA showed the complete regression of IMH, recanalization of the arterial lumen, prolonged irregular MCA stenosis. Neurological deficit regressed significantly.

Objective: To analyze clinical and neuroimaging data in patients with neck pain and headache as the only manifestation of the internal carotid artery (ICA) dissection (ICAD) and vertebral artery (VA) dissection (VAD)., Material and Methods: One hundred and sixty-one patients (mean age - 37.4±4,99 years, 84 women, 52%) with cervical artery dissection (CAD) verified by magnetic resonance imaging (MRI) were enrolled. Neck pain and headache were the only CAD manifestation in 33 patients (mean age 37,3±7,4 yars, 28 women, 85%)., Results: The localization of the dissections in these patients was the following: one VA (15 patients), two VA (9), one ICA (7), two ICA (1), one ICA + two VA (1). The whole number of dissected arteries was 45: extracranial localization - 38, extra-intracranial - 6, intracranial - 1. Dissection led to stenosis of the arterial lumen in 41 arteries, to occlusion - in 2 and to dual lumen in 2 arteries. Small aneurism was found in 4 arteries. Combination of headache and the neck pain was observed in 26 out of 33 patients (79%), the only headache in 4 patients, the only neck pain in 3 patients. Along with this, 9 out of 24 VAD patients had the shoulder and/or arm pain. Headache in VAD patients was located more often in the occipital region (18 out of 24) that had never been observed in ICAD patients (p=0.0009). Fronto-temporal pain was observed more often in ICAD patients (5 out of 8 patients) than in VAD (2 out of 24 patients) (p=0.003). Neck pain in all VAD patients in comparison with 3 out ofI8 [CAD patients had posterior localization (p=0,007). Anterolateral neck pain was observed in 4 out ofI8 ICAD patients and in no patients with VAD (p=0.0009). The pain appearance was abrupt in all ICAD patients and most of the VAD patients. In 8 VAD patients the pain has been increasing during several hours. The pain intensity was severe in 19 patients, moderate in 12 and mild in 2. The characteristics of the pain were as following: constrictive/dull (26 patients), throbbing (1 patient) or combined (6 patients). Pain was increasing in a stepwise manner during the first days in 14 out of 24 VAD patients and in no one of ICAD patients (p=0.008). The mean pain duration period was 31 8 ± 15,7 days. Pain relief drugs were ineffective or had a short effect in 97% of patient., Conclusion: Isolated pain is more characteristic for women with VAD. Usually pain is presented as a combination of headache and neck pain. Pain localization, mode of appearance and the course are different in VAD and ICAD. The rarity of occlusion among patients with <> manifestation let to suggest that the intramural hematoma in this group of patients spreads to the adventitia that can reflect media weakness. Arterial wall changes underlying its weakness seem to be sex-hormone dependent taking into consideration the high predominace of women in cad manifested by isolated pain.

We present a medical history of a 30-year old male patient with fatal ischemic stroke, resulting from the right internal carotid artery (ICA) dissection provoked by repeated head tilts and verified by magnetic resonance imaging and pathomorphological examination. At admission, the high level of creatine phosphokinase (5284 un/ml, normal level<171) in the blood was found, the coagulation parameters were normal. Autopsy revealed intramural hematoma (IMH), which was located between the media and adventitia of the arterial wall, began at 3 cm above the common carotid artery bifurcation and extended to the base of the skull. The lumen of the ICA at the level of the IMG and intracranial parts as well as of the middle cerebral artery was occluded by the thrombus. The histological examination of the right ICA wall found splitting, thinning, fragmentation, disrupters of internal elastic membrane, severe media fibrosis, myocyte necrosis at the site of the dissection with the surrounding leukocyte infiltration, as well as lymphocytic infiltrates, clusters of eosinophils in adventitia. Similar changes, except myocyte necrosis, were also found in intact (non-dissected) brain supplying arteries. In general, they were similar to those in fibromuscular dysplasia (FMD). Histochemical and electron microscopic studies of skeletal muscles showed signs of mitochondrial cytopathy. The authors discuss the relationship between the dissection, FMD and mitochondrial pathology.

Objective: To compare demographic, clinical, and imaging characteristics of patients with internal carotid artery dissection (ICAD) and vertebral artery dissection (VAD) in a Russian population., Material and Methods: One hundred fifty-two consecutive patients (74 males, 49%; mean age - 37.0±10.3 years) with cervical artery dissection (ICAD - 85 patients, 56%; VA - 62 patients, 41%; ICA+VA - 5 patients - 3%) verified by MRI/MRA were studied. Five patients with both ICAD and VAD were excluded from analysis., Results: Patients with ICAD more often were men (63%, p<0.0001), while patients with VAD were women (69%, p<0.0001), age distribution was similar (37.4±11.2 and 36.2±9.4 years, p>0.05). The main precipitating events for VADs were neck movements, prolonged static turning of the head, physical exertion (57% vs 28% in ICAD, p=0.0009). Head trauma within the previous month was more often reported by ICAD patients than VAD patients (21% vs 7%, p=0.0295). Clinically ICADs more frequently manifested by ischemic stroke (IS) then VADs (82% vs 55% p=0.0004), but more rarely by isolated cervical pain/headache (10% vs 35%, p<0.0001). 85% patients with dissections had neck/headache preceding cerebral ischemia: isolated neck pain (27%, p=0.0001) or a combination of neck pain with headache (55%, p=0.0004) were characteristic of VADs while headache was typical for ICADs (71%, р=0.0001). According to MRI, bilateral ICADs were found more rarely than bilateral VADs (10% vs 31% p=0.0029). Arterial occlusion was more common for ICADs (61% vs 20%, p<0.0001), double lumen was found only in VAD patients (6%, p=0.0121), and aneurysms were revealed with similar frequency (ICAD 7%, VAD 5%)., Conclusion: There were significant differences between patients with ICAD and VAD in terms of gender distribution, precipitating events, clinical and imaging features. Different embryonic origin of ICA and VA, their anatomical differences, and intramural hematoma location in relation to intima and adventitia may underlay these differences.

The aim of this study was to analyze clinical and neuroimaging manifestations of vertebral artery (VA) dissection. Twenty seven patients (19 men, 8 women, mean age 34.1±6.1) with the VA dissection were enrolled. All the patients underwent MRA, neck MRI (T1 f-s, T2 f-s) and head MRI. Twenty six of 27 patients had follow-up MRA/MRT studies: during the acute period and after 2 months or later. Clinical manifestations of VA dissection included ischemic stroke (IS, 52%), transient ischemic attack (TIA, 4%) and isolated neck pain/headache (44%). Ninety two percent of patients in the group of patients with isolated pain and 53% in the group with brain ischemia were women. Bilateral dissection of VA was found in 10 of 27 patients (37%), concomitant internal carotid artery dissection -- in 2 patient (7,4%). In 93% of the patients, IS/TIA was associated with neck pain and/or headache. In 64% patients, the pain occurred after neck movements or mild head trauma. The pain preceded brain ischemia symptoms by a few days/2--3 weeks (80%) or appeared simultaneously with them (13%). Symptoms of brain ischemia developed abruptly (82%) usually in wakeful state (80%) during rotation/ bending of the head. Most patients (93%) had complete or good regress of neurological deficit. MRA/MRI revealed hemodynamically insignificant VA stenosis (92%), VA occlusion (5%), increasing of the external VA diameter (100%), dual lumen (8%) and small dissecting aneurysm (11%). In 4 of 6 stroke patients studied within the first week, the signs of arterial embolism were found. The follow up MRA/MRI showed the regress of all stenosis and recanalization of one of two occlusions. In patients with isolated pain, dissections occurred more often in the V1--V2 segments of VA (83%), while in patients with IS/TIA the dissections were mostly found in the V3--V4 segments (47%) (р<0.05). The patients with IS/TIA had more prominent VA stenosis and smaller external arterial diameters in comparison with patients with isolated pain. This suggests the subintimal localization of intramural hematoma (IMH) in the group of ischemic manifestation and subadventicial localization of IMH in patients with isolated head/neck pain. Clinical manifestations of VA dissection depend on the IMH localization. The main mechanism of brain ischemia appears to be an arterial embolism by clotted IMH fragments from the secondary intimal tear. It is suggested that in patients with isolated pain, the media may be weaker than in patients with brain ischemia that in turn promotes subadventicial IMH propagation.