ISCHEMIC STROKE / VASCULITIS
Takayasuova arteritida
Created 24/05/2023, last revision 10/11/2023
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- 10 mg PO twice daily
- 5mg IV once daily
Management
Etiology
- Item 2
Ocular vascular disorders
Ischemic optic neuropathy (ION) - anterior (AION)
- arteritic
- non-arteritic
- posterior (PION)
Central retinal vein occlusion (CRVO) → more
(the most common retinal vascular occlusive disorder)
- non-ischemic (venous stasis retinopathy – VSR) – usually benign condition [Hayreh, 1983]
- ischemic (hemorrhagic retinopathy – HR) – the risk of severe visual impairment
Hemi-central retinal vein occlusion (HCRVO)
- non-ischemic (venous stasis retinopathy)
- ischemic (hemorrhagic retinopathy)
Branch retinal vein occlusion (BRVO)
- major BRVO
- macular BRVO
Central retinal artery occlusion (CRAO)
- arteritic CRAO (giant cell arteritis) – approx. 5%
- non-arteritic permanent CRAO (NA-CRAO)
- non-arteritic transient CRAO
- CRAO with cilioretinal artery sparing (central vision maintained to varying degrees)
Branch retinal artery occlusion (BRAO)
- permanent BRAO
- transient BRAO
Cilioretinal artery occlusion
- anterior (AION)
- Item 3
Target Content3
- Item 4
Target Content4
ALPRAZOLAM
alprazolam (NEUROL / XANAX / ALPRAZOLAM)
tablets: 0.25 / 0.5 / 1 mg
- starting dose for anxiety: 0.25 mg taken 2-3 times a day
- elderly patients may start with a lower dose of 0.125 mg taken 2-3 times a day
- gradually increase until anxiety is controlled (usually 0.2-1 mg 3 times a day)
- the usual maximum dose: 3 mg/day
- discontinuation: decrease the daily dose of alprazolam by 0.25 mg every three days
- hypersensitivity to benzodiazepines, alprazolam, or to any of the excipients
- myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome and severe hepatic insufficiency
bromazepam (LEXAURIN / LECTOPAM)
tablets: 1.5 mg / 3 mg- starting dose for anxiety: 1.5 mg taken 2-3 times a day
- elderly patients may start with a lower dose
- elderly patients may start with a lower dose
- gradually increase until anxiety is controlled (usually 1.5-3 mg 3 times a day)
- the usual maximum adult dose: 9 mg/day
- discontinuation: the drug should never be abruptly stopped but slowly tapered off under medical supervision
- bromazepam binds to the GABA-A receptor producing a conformational change and potentiating its inhibitory effects
- short-term treatment of insomnia, short-term treatment of anxiety or panic attacks, and the alleviation of the symptoms of alcohol- and opiate-withdrawal
- hypersensitivity to benzodiazepines, bromazepam, or to any of the excipients
- myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome
- starting dose for anxiety: 1.5 mg taken 2-3 times a day
alprazolam (NEUROL / XANAX / ALPRAZOLAM)
tablets: 0.25 / 0.5 / 1 mg
- starting dose for anxiety: 0.25 mg taken 2-3 times a day
- elderly patients may start with a lower dose of 0.125 mg taken 2-3 times a day
- gradually increase until anxiety is controlled (usually 0.2-1 mg 3 times a day)
- the usual maximum dose: 3 mg/day
- discontinuation: decrease the daily dose of alprazolam by 0.25 mg every three days
- hypersensitivity to benzodiazepines, alprazolam, or to any of the excipients
- myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome and severe hepatic insufficiency
alprazolam (NEUROL / XANAX / ALPRAZOLAM)
tablets: 0.25 / 0.5 / 1 mg
- starting dose for anxiety: 0.25 mg taken 2-3 times a day
- elderly patients may start with a lower dose of 0.125 mg taken 2-3 times a day
- gradually increase until anxiety is controlled (usually 0.2-1 mg 3 times a day)
- the usual maximum dose: 3 mg/day
- discontinuation: decrease the daily dose of alprazolam by 0.25 mg every three days
- hypersensitivity to benzodiazepines, alprazolam, or to any of the excipients
- myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome and severe hepatic insufficiency
alprazolam (NEUROL / XANAX / ALPRAZOLAM)
tablets: 0.25 / 0.5 / 1 mg
- starting dose for anxiety: 0.25 mg taken 2-3 times a day
- elderly patients may start with a lower dose of 0.125 mg taken 2-3 times a day
- gradually increase until anxiety is controlled (usually 0.2-1 mg 3 times a day)
- the usual maximum dose: 3 mg/day
- discontinuation: decrease the daily dose of alprazolam by 0.25 mg every three days
- hypersensitivity to benzodiazepines, alprazolam, or to any of the excipients
- myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome and severe hepatic insufficiency
Prognostic value of IMT measurement
- not only atherosclerotic plaques but IMT as well can be used to quantify atherosclerosis burden in asymptomatic patients
- IMT should be assessed in each extracranial ultrasound exam
- an increase in the intima-media thickness is the first stage of atherosclerosis, and if untreated, it is followed by plaque formation
- clinical and epidemiologic studies demonstrated an association of IMT with coronary artery disease (CAD), stroke, and peripheral vascular disease (PAD) (ROTTERDAM, ACAPS trials ) [Lorenz, 2007]
- thickening of IMT correlates with the occurrence of traditional vascular risk factors (BMI, hypertension, hypercholesterolemia, diabetes, smoking)
- some authors recommend including IMT and the AS plaques presence among the classic vascular risk factors [Chambless, 2010]
- some publications question the importance of IMT in the CV events predictions [Costanzo, 2010] [Ruijter, 2012]
- detection of subclinical atherosclerosis is important in patients with borderline risk and multiple risk factors, as it moves the patient to the high-risk category (≥ 5% by SCORE) with all therapeutic consequences
- pharmacological studies have shown a reduction in the rate of progression of IMT on hypolipidemics and antihypertensives (ACAPS, METEOR)
- rosuvastatin did not induce disease regression
- on the other hand, a meta-analysis of 41 randomized trials showed regression of cardiovascular events on hypolipidemics but did not show a relationship between a decrease in CV events and regression of the IMT [Costanzo, 2010]
- an increase in IMT can also be found in non-atherosclerotic diseases (e.g., Takayasu arteritis)
Etiology
my-button2 – transparent
bromazepam (LEXAURIN / LECTOPAM)
tablets: 1.5 mg / 3 mg- starting dose for anxiety: 1.5 mg taken 2-3 times a day
- elderly patients may start with a lower dose
- elderly patients may start with a lower dose
- gradually increase until anxiety is controlled (usually 1.5-3 mg 3 times a day)
- the usual maximum adult dose: 9 mg/day
- discontinuation: the drug should never be abruptly stopped but slowly tapered off under medical supervision
- bromazepam binds to the GABA-A receptor producing a conformational change and potentiating its inhibitory effects
- short-term treatment of insomnia, short-term treatment of anxiety or panic attacks, and the alleviation of the symptoms of alcohol- and opiate-withdrawal
- hypersensitivity to benzodiazepines, bromazepam, or to any of the excipients
- myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome
- starting dose for anxiety: 1.5 mg taken 2-3 times a day
Clinical presentation
- závratě a synkopy (> 50%)
- ischemické CMP
- ICH (v ruptury důsledku aneuryzmat)
- zřídka poruchy vizu (poruchy ZP, amaurosis, retinální hemoragie)
- sekundární hypertenze (z postižení renálních arterií)
- diagnostické je oslabení pulsu (“bezpulsová nemoc“), rozdíl na HKK > 20mm Hg
- 98% pacientů má chybějící puls na alespoň jedné končetině
- Raynaudův fenomén
- končetinové klaudikace
- aortální regurgitace (20-25%)
TABS not changing to accordion on mobile
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- závratě a synkopy (> 50%)
- ischemické CMP
- ICH (v ruptury důsledku aneuryzmat)
- zřídka poruchy vizu (poruchy ZP, amaurosis, retinální hemoragie)
- sekundární hypertenze (z postižení renálních arterií)
- diagnostické je oslabení pulsu (“bezpulsová nemoc“), rozdíl na HKK > 20mm Hg
- 98% pacientů má chybějící puls na alespoň jedné končetině
- Raynaudův fenomén
- končetinové klaudikace
- aortální regurgitace (20-25%)
Diagnostic evaluation
Imaging methods
- zobrazovací metody – vícečetné koncentrické stenózy aorty a jejích větví, ždy vyšetřit i sestupnou aortu a renální tepny !
- SONO mag. tepen (“macaroni sign”)
- DSA
- MRA
- CTA
- FDG PET/CT
- průkaz zánětlivého postižení tepen
[Chrapko, 2015] - hypometabolismus v některých oblastech CNS [Berlit, 2010]
- průkaz zánětlivého postižení tepen
- SONO mag. tepen (“macaroni sign”)
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Blood tests
- ↑CRP, FW > 40mm (normální hodnoty nevylučují aktivní chorobu)
- anémie (většinou lehká)
- leukocytóza
- ↑ metaloproteinázy MMP-2, MMP-3 a MMP-9
Stroke prevention
- antiagregancia → viz zde [Souza, 2010]
- léčba hypertenze (problém s hodncoením TK při stenóze/okluzi a.scl.)
- dieta s nízkým obsahem Na+
- ev. PTA/STNT nebo bypassové operace (vč končetinových a renálních tepen)
- lepší výsledky jsou v obodobí remise
Immunosupressive therapy
- v úvodu PREDNISON 1 mg/kg, během několika týdnů postupně snižovat, cílová dávka je individuální (dle zánětlivých markerů a klinického obrazu)
- po dosažení remise (pokles FW, CRP, úprava anemie) ponechat na udržovací dávce 5–10 mg/den po dobu 1–2 let
- při taperingu hrozí relaps
- při dlouhodobé léčbě nutná prevence osteoporózy- např. Caltrate PLUS 1-0-1 nebo Kombi-Kalz 1000/880 1-0-0
- ev. kortikoidy kombinovat s imunosupresivy či imunomodulancii
Imunosupresiva – cytostatika
- cca 50-70% pacientů vyžaduje doplňující léčbu imunosupresivy
- u méně agresivních forem:
- azathioprin (IMURAN) 1-2 mg/kg/den
- mykofenolat (CELLCEPT)
- azathioprin (IMURAN) 1-2 mg/kg/den
- u agresivních forem:
- metotrexát 0.15-3 mg/kg/den
- cyklofosfamid (ENDOXAN) 2mg/kg/den
- metotrexát 0.15-3 mg/kg/den
Nová imunosupresiva [Mekinian, 2015]
-
- monoklonální protilátka proti receptoru pro IL 6 – tocilizumab (ROACTEMRA)
- TNF alfa blokátor – u rezistentních stavů
- monoklonální protilátka proti receptoru pro IL 6 – tocilizumab (ROACTEMRA)
Follow up
- sledování rozsahu změn, sledování šířky stěny, progrese stenóz
- MR krku + MRA
- neurosonologie
- CT angiografie
- CRP nespolehlivé
- FW – pokles při remisi jen u cca 60%, nespolehlivý marker [Matsuyama,2003]
- metaloproteinázy [Matsuyama,2003]
- MMP-2 diagnostická > 800 ng/ml
- relaps – MMP-3 > 100 ng/ml a MMP-9 > 75ng/ml
Differential diagnosis
- hypertensive arteriolopathy is the most common cause of intracerebral hemorrhage
- the relative risk of ICH in a patient with arterial hypertension compared to an individual without hypertension is approximately 4
- hypertension leads to bleeding by two mechanisms:
- rupture of an artery affected by chronic hypertension
- an acute or subacute severe hypertension leading to rupture of a previously unaffected artery (malignant hypertension)
- typical localization: basal ganglia, thalamus, cerebellum, pons
- a secondary propagation of hematoma into the ventricles (hemocephalus) or SA space is possible
- a secondary propagation of hematoma into the ventricles (hemocephalus) or SA space is possible
- hypertension leads to hypertrophy and degeneration of the media of small arteries (lipohyalinosis, fibrinoid necrosis)
- the findings suggestive of a hypertensive etiology:
- history of hypertension
- typical ICH localization
- absence of any other apparent cause of bleeding
- left ventricular hypertrophy
- leukoaraiosis on CT scan or MRI
- hypertensive retinopathy
- high blood pressure on admission is not a conclusive indicator of hypertensive disease; it can be a consequence of a stress reaction and intracranial hypertension
Imunosupresiva – cytostatika
- cca 50-70% pacientů vyžaduje doplňující léčbu imunosupresivy
- u méně agresivních forem:
- azathioprin (IMURAN) 1-2 mg/kg/den
- mykofenolat (CELLCEPT)
- azathioprin (IMURAN) 1-2 mg/kg/den
- u agresivních forem:
- metotrexát 0.15-3 mg/kg/den
- cyklofosfamid (ENDOXAN) 2mg/kg/den
- metotrexát 0.15-3 mg/kg/den
Nová imunosupresiva [Mekinian, 2015]
-
- monoklonální protilátka proti receptoru pro IL 6 – tocilizumab (ROACTEMRA)
- TNF alfa blokátor – u rezistentních stavů
- monoklonální protilátka proti receptoru pro IL 6 – tocilizumab (ROACTEMRA)
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Differential diagnosis
- compensate blood pressure (BP) in all ICH patients, start as soon as possible after bleeding
- combine pharmacological and non-pharmacological approaches
- target BP: < 130/80 mm Hg
- reduce salt uptake
- avoid smoking, alcohol and drug abuse
- treat sleep apnea if present
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- there is not enough evidence to discontinue the hypolipidemic medication (AHA/ASA 2015 IIb/C)
