[Transforming growth factor beta in patients with cervical artery dissection]. / Transformiruyushchii faktor rosta beta u bol'nykh s dissektsiei vnutrennikh sonnykh i pozvonochnykh arterii.

OBJECTIVE: To evaluate transforming growth factor beta (TGF-ß) in patients with cervical artery dissection (CeAD). MATERIAL AND METHODS: TGF-ß 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-ß study was 41.6±9.8 years; the proportion of women was 51%. TGF-ß 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-ß1 and TGF-ß2 were elevated in patients with CeAD patients compared with the control: TGF-ß1 - 4990 [3950; 7900] pg/ml vs. 3645 [3230; 4250] pg/ml, p=0.001; TGF-ß2 - 6120 [4680; 7900] pg/ml vs. 3155 [2605; 4605] pg/ml, p=0.001. The highest TGF-ß1 and TGF-ß2 levels were noted at 2-3 months of the disease. There was no correlation between the TGF-ß level and various clinical and angiographic parameters. CONCLUSION: Increased TGF-ß level confirms that CeAD patients have connective tissue disorder that underlies the arterial wall weakness. A higher TGF-ß level at 2-3 months of CeAD seems to be connected with an active reparative process in arterial wall after dissection. TGF-ß can be used as a biomarker of connective tissue dysplasia in patients with CeAD.

[The efficacy and safety of Erenumab in patients with high-frequency episodic migraine according to the first Russian real-life study of the Research Center of Neurology]. / Effektivnost' i bezopasnost' erenumaba u patsientov s chastoi epizodicheskoi migren'yu po dannym rossiiskogo issledovaniya real'noi klinicheskoi praktiki Nauchnogo tsentra nevrologii.

OBJECTIVE: To assess the effectiveness and safety of Erenumab, a monoclonal antibody to calcitonin gene-related peptide receptors, in patients with high-frequency episodic migraine (HFEM) in real-life study. MATERIAL AND METHODS: 35 patients with HFEM without aura (≥8-14 attacks per month) (30 females, mean age 32.4±8.1) received monthly subcutaneous administration of Erenumab 70 mg for 3 months. The primary endpoint was the change in monthly migraine days (MMDs) from baseline, the secondary endpoint was the proportion of patients who achieved a 50% reduction in the number of days with headache. The change in pain intensity, change in the number of days of use of acute migraine-specific medication, the effect on daily activity (HIT-6 scale, MIDAS), anxiety and depression (the Hospital Anxiety and Depression Scale) were assessed. RESULTS: At the end of the third month Erenumab decreased MMDs by 5±3.6 (p=0.00000). A 50% reduction in the mean number of migraine days per month was achieved for 60% of patients, the intensity of headache according to the visual analogue scale from 8±1.2 points to 5±2 points (p=0.00000), monthly analgesics intake passed from 11±7 to 4.5±3.7 (p=0.000001). 25.7% of patients did not respond to treatment, showing less than a 30% decrease in the number of days with headache. A decrease in pain intensity correlated with a decrease in anxiety (from 8±4 to 6±4 points (p=0.003)) and depression (from 6±4 to 4±3 points (p=0.0004)) according to HADS, reduced HIT-6 scale from 65±6 to 55±7 points (p=0.00000) and MIDAS from 45 [33; 67] points to 16 [5; 33] (p=0.000004)). Patients reported good tolerability of Erenumab. 25.7% of patients noted a tendency to constipation. No patient discontinued treatment due to adverse events. CONCLUSION: Real-life study confirmed the efficacy and safety of Erenumab in the treatment of HFEM, a decrease in the severity of comorbid anxiety and depression, and social maladjustment.

[Cervical artery dissection in women: relationships with pregnancy and postpartum period]. / Dissektsiya vnutrennei sonnoi i pozvonochnoi arterii u zhenshchin: vzaimootnoshenie s beremennost'yu i poslerodovym periodom.

OBJECTIVE: To study the frequency of CeAD that developed during pregnancy or in post partum period among all CeADs in women; to study the course of pregnancy in women with prior CeAD. MATERIAL AND METHODS: 162 women (mean age 37.1±4.1 years) with CeAD we examined at the Research Center of Neurology (Moscow), 98% women were studied during last 15 years. 140 women were of childbearing age (≤45 years, mean age - 35±2.8 years). All patients were interviewed whether or not CeAD occurred during pregnancy or in post partum period (CeADPPP). Obstetric history before and after CeAD was studied in 57 women of childbearing age (average age - 35.9±7.3 years at CeAD development). RESULTS: CeADPPP developed in 6 out of 162 all female patients (3.7%) or of 140 childbearing age patients (4.3%). It occurred 2-6 months (4 patients) and 10 days after delivery (1 patient), or on the 25th week of pregnancy (1 patient). CeADPPP patients were younger than patients with CeAD out of pregnancy or postpartum period (29.8±8 years vs 35.1±6.7 years, p>0.05). CeADPPP in comparison with CeAD outside these periods more often involved internal carotid artery (ICA) (50% vs 35%, p=0.666), more often occurred in 2-3 arteries (50% vs 31%, p=0.386) and more often was accompanied by dissecting aneurysm development (50% vs 8%, p=0.013). After CeAD, 18 out of 57 patients in whom obstetric history was studied, including 3 patients with postpartum dissection had 29 pregnancies. The pregnancy outcomes were as follows: childbirth (17 pregnancies, 59%), fetal loss (8 pregnancies, 27%) and medical abortion (4 pregnancies, 14%). Delivery occurred on average 4.5±2.061 years after CeAD in women aged 33.0±4.25 years (cesarean section - 15 patients). Fetal loss occurred at 7.4±3.5 weeks of pregnancy in women aged 37.6±3.13 years on average 2.7±1.4 years after CeAD. Fetal loss frequency after CeAD was higher than before it (27% vs 7%, p=0.016). There were no CeAD recurrences during pregnancy and postpartum period in women who had previously undergone CeAD. CONCLUSION: CeADPPP frequency among all dissections in women is 3.7-4.3%. The risk of CeAD recurrence during pregnancy or the postpartum period after prior CeAD is very low. The risk of fetal loss during 2.7±1.4 years after CeAD is higher than before it (27% vs 7%). Hormonal and growth factors associated with pregnancy and the postpartum period is suggested to contribute to cervical artery wall damage. It is possible that the prolonged action of some of these factors may disrupt the placental vessels formation, predisposing to miscarriage.

[Internal carotid artery dissection in patients with Turner's syndrome]. / Dissektsiya vnutrennei sonnoi arterii u bol'nykh s sindromom Shereshevskogo­Ternera.

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.

White matter hyperintensity in different migraine subtypes.

The diagnostic value of white matter hyperintensities (WMH) in different types of migraineare unknown. To evaluate the WMH pattern of different subtypes in migraine patients with no vascular risk factors. 92 migraine patients (73 females, mean age 34.6 ± 8.9; 61 episodic migraine, 31 chronic migraine, 36 migraine with aura, 56 migraine without aura) without vascular risk factors underwent brain MRI (3 T). We also included a matched healthy control group with no migraine (n = 24). The prevalence of WMH in different types of migraine was similar and ranged from 38.7 to 44.4%; the control group showed no WMH at all. Lesions were located within frontal, parietal and temporal lobes (in order of decreasing incidence) in juxtacortical and/or deep white matter. WMH appeared as round or slightly elongated foci with a median size of 2.5 mm [1.5; 3]. Total number, size and prevalence of WMH by lobes and white matter regions were similar between groups, and no interaction with age or sex was found. The number of lesions within the frontal lobe juxtacortical white matter correlated with the age of patients (r = 0.331, p = 0.001) and the duration since migraine onset (r = 0.264, p = 0.012). Patients with different migraine subtypes and without vascular risk factors are characterized by a similar pattern of WMH in the absence of subclinical infarctions or microbleedings. Therefore, WMH have no relevant prognostic value regarding the course of migraine and vascular complications. WMH pattern may be used to differentiate migraine as a primary disorder and other disorders with migraine-like headache and WMH.

[Aneurysms and pathological tortuosity of the internal carotid and vertebral arteries in patients with dissection of these vessels: a results of long-term study]. / Anevrizmy i patologicheskaya izvitost' vnutrennikh sonnykh i pozvonochnykh arterii u bol'nykh s dissektsiei etikh sosudov: rezul'taty dolgosrochnogo issledovaniya.

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.

[Fibromuscular dysplasia and its neurological manifestations]. / Fibromyshechnaya displaziya i ee nevrologicheskie proyavleniya.

The authors present the current data on the classification, epidemiology, etiology, neurological manifestations, prognosis, diagnosis, and treatment of patients with fibromuscular dysplasia (FMD). The review is based on the selection of publications by searching PubMed for keywords from the first sources until March 2019. FMD is a segmental non-atherosclerotic and non-inflammatory disease of large- and medium-caliber arteries leading to their stenosis. The disease occurs mostly in women (90%), and manifests itself in the 5th decade of life. In the cerebrovascular form of FMD, the extracranial internal carotid artery and the vertebral artery are usually affected. Diagnosis is based on the identification of alternation of narrowing and dilation of arteries using angiography (the string of beads sign (multifocal form)). Neurological manifestations include headache, tinnitus, and ischemic stroke, usually due to the dissection or stenosis, rarely, intracerebral or subarachnoid hemorrhages. The prognosis in most cases is favorable, relapses of strokes are rare. Treatment includes antiplatelet agents, if they are ineffective to prevent recurrence of ischemic stroke, endovascular treatment is carried out. Approaches to the treatment of intracranial aneurysms do not differ from those in patients without FMD.

[Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids]. / Khronicheskoe limfotsitarnoe vospalenie s perivaskulyarnym nakopleniem kontrastnogo veshchestva v mostu golovnogo mozga, otvechayushchee na lechenie steroidami.

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.

[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.

[Anamnestic headache in patients with cervical artery dissection: clinical characteristics and pathogenetic mechanisms]. / Anamnesticheskaia golovnaia bol' u bol'nykh s dissektsiei magistral'nykh arterii golovy: klinicheskie osobennosti i mekhanizmy razvitiia.

AIM: To study the frequency and characteristics of headache which is in the past history (HPH) of patients with cervical artery dissection (CeAD) and evaluate with the help of EEG and visual evoked potentials (VEP) the role of central mechanisms in its development. MATERIAL AND METHODS: Two hundred and twenty-seven patients with CeAD verified by neuroimaging were studied. All patients were interviewed about the presence of a headache in the past history and its features. The comparison group comprised 35 patients (mean age - 32,3±8,9 years, 77% female) with migraine. Thirty-five patients with HPH and 35 patients of the comparison group underwent EEG and VEP. RESULTS: HPH was found in 101 patients (average age of 38.5±8.5 years, 70% female) (44.5%) out of 227 patients. In 35 patients (15.4%), HPH met the International Criteria for migraine (with aura - 3.1%, without aura - 12.3%) and in 66 patients (29.1%) did not (non-migraine headache). The latter started at the age of 24.5±10.2 years, had mild/ moderate intensity (95%), diffuse localization (68%), dull/pressing/squeezing character (53%), never accompanied by vomiting and rarely by nausea (8%), photo- phonophobia (11%). HPH, which met the migraine criteria unlike migraine in the comparison group began at a later age (19.9±9.6 vs 16.2±4.4 years, p<0.03), more frequently did not have aura (80% vs 48%, p<0.003), less often was unilateral (31% vs 71%, p<0,004) and had less intensity. The visual EEG analysis less often found rhythmic disorganization in CeAD patients with HPH than in comparison group with migraine. The hyperventilation caused a slight increase in the spectral power of Teta, Delta waves in HPH patients and significant enhancement in comparison group with migraine (p<0.05). Pattern reversal VEP in patients with HPH had a greater latency and smaller amplitude of cortical responses than in comparison group with migraine (p=0.028 and =0.037, respectively). The flash VEP amplitude was lower in HPH patients than in migraine (p=0.01). CONCLUSION: HPH in patients with CeAD meets criteria of migraine in 15.4% (with aura - 3.1%, without aura - 12.3%), 29.1% patients have nonmigraine HPH. Central mechanisms, namely, the hypersensitivity of the cerebral cortex playing the main role in migraine pathogenesis, are not significant in HPH genesis. The main role appears to have peripheral mechanisms - dysplastic changes in the wall of extra- and intracranial arteries that predispose both to headache and dissection.

[Intimal rupture of the displastic middle cerebral artery wall complicated by thrombosis and fatal ischemic stroke]. / Razryv intimy pri displazii stenki srednei mozgovoi arterii, oslozhnivshiisia trombozom i razvitiem tiazhelogo ishemicheskogo insul'ta.

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.