Pearls on strokes associated with hematologic diseases

This is based on an OLD article by Martin Samuels, so newer drugs for condition are not included

Samuels MA, Thalinger K.  Cerebrovascular manifestations of selected hematologic diseases.  Seminars in Neurology 11:4 1991.

1.  Anemia-- examine the EYE.  First sign is pallor, then spindle shaped retinal hemorrages with cotton wool spots.

2.  Blood transfusions can trigger stroke in patients with Beta thallasemia (cites Logothetis J. et al. Neurology 1972;22:294-304.

3. In thrombocytopenia, intracranial hemorrhages occurs as small ring shaped hemorrhages in the gray and white matter due to capillary bleeding.Subdural, subarachnoid and epidural hemorrhages are rare in this condition.  Peripheral nerve and spinal cord hemorrhage also are rare.

4. In thrombotic thrombocytic purpura (TTP), consists of triad of thrombotic purpura, hemolytic anemia and neurologic manifestations.  Fever and renal disease are "invariably" present.  Diagnosis depends on tissue of skin, lymph node, bone marrow or spleen that show hyalinization of arterioles and platelet thrombi with small foci of parenchymal necrosis and petecchiae."Gray matter" symptoms include headache, confusion, aphasia, hemiparesis,visual changes, dysarthria, seizures, coma, vertigo. Exchange transfusion helps dramatically. Other treatments are heparin, steroids, splenectomy.

5.  In hemolytic uremic syndrome, similar to TTP, caused by immune deposits, exchange transfusion can result in dramatic improvement.  FFP without albumen also helps.

6.  Henoch-Schoenlein purpura (anaphylactoid purpura) is characterized by serosanguineous effusions into subcutaneous, submucous, and subserous tissues, esp in young adults.  Treatment is supportive.  ICH and SAH occur rarely.IgA mediated, also get renal deposits

7.  Ischemic strokes occur in 15-32 percent of patients with polycythemia vera.  The annual incidence of TIA/ stroke is 4-5 percent even in those treated with phlebotomy.  Conversely, risk of stroke is rare in secondary polycythmia.  For example, someone with congenitally cyanotic heart disease and Hct of 60 has very low risk, none occurred in a small series cited with more than 200 patient years of followup.

8.  Hyperviscosity syndrome is a major cause of stroke in patients with myeloma.  Clinical presentation is stupor, coma, drowsiness, inattention,delirium.  Fundoscopic changes include "sausage veins,"  retinal hemorrhages and exudates.  Focal events can occur in Waldenstrom's macroglobulinemia.  Plasma exchange can dramatically improve symptoms due to heavy proteins.

PFO and attributable risk with RoPE score

                        cryptogenic stroke, CS (n= 3,023)                                           

 

RoPE score          No patients   Prevalence PFO   PFO attributable   

 

0-3                         613               23(19-26)             0                          

4                            511               35(31-39)             38 (25-48)              

5                            516               34 (30-38)            34 (21-45)             

6                            482               47(42-51)             62 (54-68)         

7                            434               54(49-59)             72 (66-76)            

8                            287               67(62-73)             84 (79-87)         

9-10                       180                73(66-79)             88(83-91)         

 

 

                       cryptogenic stroke (CS) with PFO (N=1,324)

                            No CS+PFO    est 2 yr TIA/CVA (Kaplan-Meier) 

 

                                                                                   

0-3                         108                20(12-28)

4                            148                12(6-18)

5                            186                  7 (6-18)

6                            236                  8 (4-12)

7                            263                  6 (2-10)

8                            233                  6 (2-10)

9-10                       150                   2(0-4)

attributable risk PFO based on Bayes' theorem

 

derivation of data used to make RoPE database

RoPE score for PFO

RoPE score for PFO (Risk of Paradoxical Embolus)

Characteristic    Points

No history of
DM                         1
stroke/TIA              1
HTN                       1
nonsmoker             1
cortical infarct        1

Age
18-29                      5
30-39                      4
40-49                      3
50-59                      2
60-69                      1

total score  -- add sum of parts
cut score used in many articles is 7

source Neurology 2013 au Thaler
 

RoPE score, PFO and CS

Thaler DE, Ruthazer R, Weimar C., et al.  Recurrent stroke predictors differ in medically treated patients with pathogenic v. other PFO's.  Neurology 2014; 83: 221-226.

 

The RoPE score, "Risk of Paradoxical Embolism" score estimates the probability that a PFO discovered in a cryptogenic stroke (CS) patient is incidental or pathogenic, based on Bayes theorem.  Patients with high RoPE score (younger, no vascular risk factors, and a superficial infarct) are more likely to have pathogenic PFO's while patients with low RoPE scores (older, vascular risk factors) are probably incidental.  Authors hypothesized that predictors of recurrent stroke should differ among high and low RoPE score patients and PFO characteristics should be les important in low RoPE score individuals. 

 

Risk factors for recurrence with 1-2.2 yrs of followup  included LOW RoPE scores (one year followup, 7 v. 4 %; two year followup 10 v. 5 %) with 4/5 recurrences being in low score subgroup 

 

Patients with TIA had more recurrent events (HR 1.69) but there was no interaction with RoPE score.

 

Variable associated with risk in low RoPE group include older age, those treated with antiplatelet drugs after initial event.

Variables associated with recurrence in highRoPE score group include history of stroke or TIA, hypermobile interatrial septum, and a small shunt, but not shunt at rest. 

 

Comment of blogger

The article confirms / validates the RoPE score to some extent.  However, the point of closure is to prevent lifetime risk of paradoxical embolus, not 2 year risk.  As such, I am skeptical of the claim that risk of recurrence is lower in high RoPE score group

DJ

MELAS pearls

maternal , mitochondrial dna a3243g

1. Onset before 40
2. Clinical: hemiparesis, hemianopia, cortical blindness; seizures, dementia, migraine, muscle weakness,
3. Associated
Short stature
Hearing loss
Recurrent vomiting
Diabetes
cataracts
developmental delay , cognitive delay AFTER infancy
4. May be relapsing remitting
5. High lactic/abn muscle biopsy
6. AVOID statins and Depakote


MRI parietal-occipital, parietal temporal acute strokes
MRS lactate peak
CSF increased lactate, pyruvate and amino acids
depletes NAD+, NADH+
increases anaerobic metabolism
increases lactic acidosis

progressive strokes and vision loss before age 40
presents in childhood
dx muscle biopsy ragged red fibers on Gomori stain

Rx CoQ
carnitine
L-Arginine
B vitamins
AED's but not depakote

HERNS (RVCL)

Retinal vasculopathy with cerebral leukodystrophy aka cerebroretinal vasculopathy sysndrome aka hereditary endotheliopathy, retinopathy, nephropathy and stroke.

Features
Vision and memory loss
Seizures
Hemiparesis
Apraxia
Dysarthria
dysautonomia
AUT DOM

Onset in fourth decade
Death in five to ten years

Retinopathy is neovascularization of disc, retinal hemorrhage and macular edema.

Half patients have tumor like lesion with cortical sparing resembling malignancy.

Small white matter lesions may resemble MS

Caused by mutations of TREX1 genE
Inherited as aut dome frame shift mutation that encodes dna exonuclease

Retinopathy may respond to bevacizumab

CARASIL pearls

1.  Onset decades 3 to 5

2.  Premature alopecia occurs in teen years

3.  Cervical and lumbar spondylitis occurs in 2d and 3d decades

4.  Mutations in A serine peptides 1 on chromosome 10 q is implicated

Cadasil pearls

1. Strokes are subcortical many with classic lacunae syndromes

2. False negative genetic tests should prompt skin biopsy for granular osmiophic material in the vascular basal lsmina which is a specific finding

3. MRI finding occur in anterior temporal poles (o'Sullivan sign seen in 90 percent) but also extreme capsule and corpus callosum also are distinctive

4.  Other MRI findings are microbleeds and brain atrophy

5.  80 plus NOTCH3 mutations are identified

6.  Migraine with aura occurs in 30 percent, often in 3rd decade long before strokes

Unruptured aneurysm pearls

1. High risk patients who require screening are those with at least two first degree relatives with aneurysm or autosomal dominant polycystic kidney disease

2. Risk factors include age, female gender, family history

3. Risk of rupture in positive family history patients is 17 x higher than in predicted based on size and location in observational studies (Familial Intracranial Aneurysm study).

4. Associated diseases are Marfan syndrome, Ehler Danlos syndrome type IV, aortic coarctation, FMD, and autosomal dominant PCK (12.4 percent). Patients with PCK have increased risk of aneurysm, but their first degree relatives only have 9 percent risk

5. Modifiable risk factors for aneurysm growth include smoking, alcohol abuse and hypertension

6. MCA bifurcation aneurysms are more readily accessible to surgery.

Pearls pediatric stroke

1. Stroke may present with seizures in newborns and even older kids

2. Paroxysmal or stuttering episodes ppt by HV is typical for Moyà Moyà

3. In newborn, consider maternal factors (HTN, DM), perinatal factors, neonatal factors (congenital heart disease, dehydration, infection), and PLACENTAL vasculopathy

4. ACCP recommends against the use of alteplace in pediatric stroke outside clinical trials

5. In Toronto, UFH is used for AIS regardless of mechanism

6. The syndrome of transient cerebral arteriopathy of childhood is a well defined unilateral focal arteriopathy presumably of inflammatory origin. Features include irregular stenosis at carotid T junction. Varicella angiopathy is similar and borrelia and bartonella are also reported. Treatment may include antithrombotics, high dose pulse steroids with long taper, and acyclovir. differential includes Moyà Moyà and dissection of the carotid.

Hypercoagulable misc

1. Homocystinuria, anti phospholipid syndrome, and thrombin deficiency are some of the only syndromes associated with arterial thrombosis

2. The most common acquired thrombophilia is the apl syndrome

3. Seven percent of the white population carries the prothrombin gene mutation but it's rare in black and Asian populations

4. Inherited protein S deficiency autosomal dominant and heterozygous; homozygous is incompatible with life.

5. Protein C deficiency can be due to meningococcemia, liver disease, DIC, ARDS, methotrexate, 5FU, and cyclophosphamide.

Pearls on factor V (Leiden) mutation

1. By far the most common genetic risk factor for thrombophilia

2. Mechanism: increases thrombin production

3. Prevalence varies widely by ethnicity: 5.3 percent in whites, 2.2 percent in Hispanics, 1.3 percent in native Americans, 1.2 percent in African Americans, 0.5 percent in Asian Americans.

4. Five to ten percent of heterozygous carriers in their lifetimes; a sevenfold risk over non carriers but homozygous have an 80 fold risk.

5. 90 to 95 percent of patients with protein C resistance have a point mutation of factor V506Q.

6. Other causes of increased protein C resistance include smoking, oral contraceptives, pregnancy, HRT use, cancer, and anti phospholipid syndrome

7. Syndrome is convincingly linked to venous but not arterial thrombotic events

8. Testing in nonwhite populations is low yield

9. Testing in ischemic stroke in absence of a right to left shunt is low yield

10. In presence of a right to left shunt screening for Dvt with leg ultrasound and pelvic venography is useful

thrombolysis and aneurysms

Post-Thrombolysis Hemorrhage Risk of Unruptured Intracranial Aneurysms; Chen F, Yan S, Jin X, Lin C, Cao J; European Neurology 73 (1-2), 37-43 (Nov 2014)

 

Background/Aims: It has been questioned whether patients with unruptured intracranial aneurysms (IAs) are at a greater risk for the development of intracerebral hemorrhage (ICH) following thrombolytic therapy. We thus performed a meta-analysis to better quantify the risk of post-thrombolysis ICH in patients with acute ischemic stroke and incidental IAs. Methods: We searched PubMed, Web of Science and EMBASE for studies assessing ICH risk in patients with acute ischemic stroke treated with thrombolysis, in relation to the presence of pretreatment IAs. A fixed-effects model meta-analysis was performed. Results: We identified four studies totaling 707 participants receiving intravenous thrombolysis. The prevalence of unruptured IAs was 6.8%. Pooled analysis demonstrates relative risk (RR) for the presence of unruptured IAs and the development of any ICH to be 1.204 (95% CI 0.709-2.043; p = 0.492; I(2) = 0.0%). The RR for sICH is 1.645 (95% CI 0.453-5.970; p = 0.449; I(2) = 28.1%). Conclusion: Intravenous thrombolysis was safe among patients with acute ischemic stroke and incidental unruptured IAs. Future prospective studies with much larger sample sizes are required to clarify the significance of the association between pre-existing unruptured IAs and the development of post-thrombolysis ICH. © 2014 S. Karger AG, Basel.

11

Subarachnoid hemorhage and growth hormone treatment in childhood

Poidvin A, et al.  GH treatment for childhood short stature and risk of stroke in early adulthood. Neurology; 2013; 83: 780-6.

 

6874 children with idiopathic GH deficiency or short stature who stated GH treatment had  rate of hemorrhage from 3.5 to 7.0 compared registry rates. from 1985-96 

 

Editorial (Ichord R) outlines ramifications on screening adults exposed to GH and counselling kids considering GH about risks, which are small but not negligible.

 

 

 

 

Small strokes causing severe vertigo. Frequency of false negative MRI's and

nonlacunar mechanisms.

 

Tehrani ASS, Kattah JC, Mantokoudis G, et al. Neurololgy 2014; 83: 169=173

 

Introduction

Out of acute vestibular syndrome (AVS)  25 % have stroke

80 % of patients with stroke have isolated dizziness/vertigo and 20 % have focal neurologic signs

35 % of strokes are missed, often with negative MRI's. 

 

Results

Out of 190 high risk  AVS presentations, 105 strokes

15  "small strokes" who underwent repeat imaging and found lesion < 10 mm in axial diameter

 

Location of stroke: lateral medulla (60 %)

Etiology Many dissections of vertebral artery, less commonly small vessel, cardiac embolus 

 

"HINTS PLUS" with the plus being a "hearing battery" bedside finger rub picks up the AICA strokes more accurately than MRI

 

My comment-

Lateral medullary infarctions have expected neurologic signs and symptoms that may be missed by physicians who do not know what to look for.  These include decreased gag/phonation, and crossed sensory symptoms (loss of st tract on one foot, dorsal column function on the other) that will pick up many or most of those. I would guess that in AVS with HINTS plus hearing eval plus careful gag/sensory exam some if not most of the strokes could be diagnosed clinically and localized accurately.  MRI is a poor test in this disease, but diagnosis is possible.

 

DJ

Blood pressure variability after thrombolysis: prognostic signficance

Delgado-Mederos E, Ribo M, Rovira A, et al.  Prognostic significance of blood pressure variability after thrombolysis in acute stroke.  Neurology 2008; 71: 552=558.

 

80 stroke patients were prospectively studies who had MCA occlusion treated with t-pa.Multiple BP measurements were obtained.  Recanalization was assessed with TCD at six hours.  NIHSS was done at baseline and 24 hours, MRS at 3 months. 

 

55 % were recanalized.  Both SBP and DBP variability were highly associated with DWI growth (done before and 36 hours after thrombolysis) and outcome, but only in patients who failed to recanalize

 

Notes-- There was a significant decline in overall SBP and DBP in recanalized but not unrecanalized patients. However BP variability was the only factor corresponding to DWI growth.  Authors speculate that treating the swings is as important as treating the outlying numbers.

 

Blogger comment-- this observational study is interesting but not powerful enough to be determinant 

Infarction in the anterior choroidal artery territory: clinical progression and prognosis factors

Chausson N, et al.  JSCD; 2014; 23:8: 2012-7.

 

Authors describe the phenotypes of  anterior choroidal stroke in heretofore unappreciated ways.  They prospectively enrolled patients with AChA disease

 

*One hundred patients were found out of 1234 total (8.1 %) who had AChA strokes

 

*  Main risk factors found were hypertension and (79 %) and diabetes (31 %). 

 

*  88 % had "lacunar" (motor syndrome in 51, sensorimotor in 23, ataxic hemiparesis in 14, isolated ataxia in 4, other 7)

*  only four patients had hemianopia

*  cardioembolic and atherothrombotic causes wee rare

*  3 % mortality but 26 % poor outcomes, invariably due to residual motor deficit and/or spasticity

* Progressive strokes were seen in 46, and 16 with fluctuations, wiht progressions over a mean of 56 hours and being almost exclusively motor

* Use of iv tpa did nto help prevent progression (tpa was used in 12/46 progressors and 9/54 nonprogressors)

* predictor of poor outcome was those who reached an NIHSS of 6 or greater, clinical progression, and infarct size > 15 mm

* Progression was nearly always due to infarct expansion on DWI

* Authors suggest new treatments are needed for this disease.

 

 

Recurrence in Intracranial atherosclerotic disease (ICAD): a stenosis based analysis

Gouvela a, et al.  JSCD, 2014: 23:8:2080-4.

Authors confirmed prior work showing extremely high recurrence rate of stroke in this type of disease:  12.3 per 100 patient years, with mean time to recurrence being 1.7 months among symptomatic intracranial stenosis (SIS) and 0.88 per 100 patient years among asymptomatic intracranial stenosis (AIS). 

They investigated 1302 patients retrospectively, with 218 strokes in 158 patients, of which 77 were symptomatic and 141 asymptomatic.  Patients with AIS were older, had more AF

blogger note-- interesting article that splits ICAD ina new way, to AIS and SIS that has very different clinical outcomes.

Odds ratio and population attributable risk of 10 factors estimated to acount for 90 % of ischemic stroke risk

Risk factor            OR              PAR    (confidence intervals available elsewhere)

 

hypertension          2.64            34.6

current smoking     2.09            18.9

waist to hip ratio    1.65             26.5

Diet risk score       1.35             18.8

Regular exercise    0.69             28.5

Diabetes mellitus   1.36             5.0

ETOH (> 30/mo)     1.51             3.8

Stress/depression   1.30            4.6

Cardiac causes       2.38            6.7

ratio apo B/A1        1.89             24.9

 

Notes

Spouses of smokers have double risk of stroke.  Much benefit of cessation occurs in first 6 months.  Cessation leads to return to baseline risk within five years.

 

Fives risk factors  related to lifestyle and risk

1. Absent current smoking

2. 30 + minutes per day of exercise

3. healthy diet

4.  moderate ETOh consumption

5.  BMI < 25

If all five risk factors are favorable,   RR is -.2, PAR is -53.

 

Cretan Mediterranean diet is the best one; those randomized to it had 70 % less CV events within 27 months

This diet contains more fat esp olive oil.  Its much lower in meat and dairy products and uses fruit as desert. It has high levels of canola nad olive oil, high fruit/vegetable/lentils/beans and nuts.  Avoid trans fats and egg yolks; meat every other day.

 

Ottawa Model of Smoking Cessation

systematic

Identify smoking status-- have you used any form of tobacco in the past six months? The past seven days?

Document-- smoking history (pack years); previous quit attempts, time to first cigarette

Advise--- "There is nothing more important that cessation. We can help you with that"

Pharmacotherapy-- readily available medicine, prescribed appropriately

Followup-- FP; telephone calls; community resources.

ACC/AHA Guisdelines for postcardiac surgery atrial fibrillation; and CABG in general

* patients with pre-existing AF receiving antiarrhythmics or rate controlling agents should be continued ont hese in postop period.

 

*  Oral beta blocker is recommended to prevent post op AF in patients undergoing cardiac surgery-- unless contraindicated

 

*  An AV nodal blocking agent is recommended for postop rate control in patients who develop postop AF

 

* Preop amiodarone decreases the incidence of AF in patients undergoing cardiac surgery  and represents appropriate prophylactic therapy for patients at high risk of AF

 

*  Its reasonable to restore sinus rhythm pharmacologically or through cardioversion among patients who develop postoperative AF

 

*  It is reasonable to administer anti-arrhytmics to maintain SR in patients with postop refractory or recurrent AF

*  Antithrombotic medication is reasonable to administer in patients who develop postop AF

 

*  Prophylactic sotalol may be considered in high risk patients. 

 

Additional points for cardiac surgery-- evidence based

 

*Matching preop and postop BP may reduce the risk of perioperative stroke or death  III/B

 

* Preop statins reduce the perioperative stroke risk in cardiac surgery  IB/A

 

*  Antiplatelet therapy eg ASA reduces the postop stroke risk without increasing the risk of bleeding complications  Ia/A

 

*  Discontinuing warfarin or antiplatelet agents in anticipation of surgery increases the risk of perioperative stroke, with the highest risk in patients with CAD

Benefit of CEA in different conditions

Degree of stensois         Studies        Recc           Risk reduction

 

Symptomatic stenosis

   70-99%                       NASCET     CEA LEVEL A       16.5 % at two years

   >60 %                         ECST               "                     11.6 % at 3 years

   50-69 %                       NASCET           "                    10.1 % at 5 years

 

 

Asymptomatic stenosis

 

>60 %                            ACAS, ACST     "                     6.3 % at five years

RISK OF HEMORRHAGE

 

-- some literature favors early surgery for patients without early ICH on CT scans

 

-- of those who hemorrhaged, hemorhhage occured 3-6 days after surgery when patients were improving or ambulatory.  They occurred in 6/900 patients studied

 

-- Dosick et al. reported 9.5 % restroke incidence with six week waiting period before CEA

 

--In NASCET 4.9 % of 103 patients  (5 patients) had restroke within 30 days of trial entry if treated medically

 

-- In a variety of studies patients operated within 3 weeks had 3 % stroke risk, those operated beyong 3 weeks had a 5.3 % stroke risk

 

 

 

 

Timing of tpa; outcomes

0-90 minites  odds ratio for favorable outcome at 3 months based on 4 point decline of NIHSS is 2.11

90-180 minutes-- odds ratio is 1.69

 

In NINDS trials, poor outcomes as defined by MRS >3 at 24 hours were predicted by NIHSS>22

OR

NIHSS>17 plus AF

Duration of dual antiplatelet therapy after implantation of drug eluting stents

Park et al. NEJM 2010; 362: 1374-82. 
Conclusion
use of dual antiplatelet therapy more than 12 months among patients who received drug eluting stents was not significantly more effective than aspirin monotherapy. 

Lenient v. strict rate control in patients with atrial fibrillation

Gelder et al.  NEJM 2010; 362: 1363-73

study of 614 patients showed that among patients with permanent AF, lenient rate control is as effective as strict rate control and is easier to achieve.

vitatops study

http://ac.els-cdn.com/S1474442210701873/1-s2.0-S1474442210701873-main.pdf?_tid=c39f01f0-f232-11e3-9c1b-00000aacb361&acdnat=1402578739_e5b1b16c09ddc46f739cdc8e3ecf08fb

 

b vitamins and folic acid was safe but not more effective than placebo to prevent strokes

Fingolimod and atrial fibrillation

Rolf et al.  Paroxysmal atrial fibrillation after initiation of fingolimod for multiple sclerosis treatment

 

42 year old male had PAF on initiation, resolution on withdrawal of, recurrence on reinitiation and reresolution permanently on discontinuation of fingolimod.  Extensive cardiac testing was negative.   This is different than the bradycardia that is known to occur with fingolimod which requires initiation with cardiac monitoring. 

 

Authors note that fingolimod is an agonist of S1P-R1,2,3 in cardiovascuklar system.  In atrial myocytes, binding of the receptors causes activation of the potassium channels leading to an inward K current and decreased firing rate.  Therefore drug causes bradycardia or AV conduction blockade.  There is in animal models, S1P induced reperfusion tachyarrythmias. 

IV thrombolysis and renal disease

Neurology 2013; 81: 1780-8.

Studied 4780 ivt treated patients, of whom 25.5 % had a low GFR below 60 mL/min.  Low GFR was significantly associated with poor 3 month outcome  death and sICH; lower GFR "might be a better risk indicator than age" and a decrease by 10 mL/min/1.73 m@ has a similar impact on death or SIC as one point on the NIHSS

IV tpa is safe in Chagas disease related strokes

Neurology 2013;81:1773-5.  Out of a series of 240 patients in Brazil, 24 (13.8%) had positive serologic testing for Chagas disease.  They more likely had heart failure and higher NIHSS but did NOT have more symptomatic intracranial hemorrhage or in hospital death than patients without.  Conclusion:  Chagas disease diagnosis does not preclude use of tpa.
editor note: does not apply to those with known Chagas disease vasculitis, and a small number was studied, and positive serology is different than having severe disease

AHA guidelines for stroke prevention in women

http://stroke.ahajournals.org/content/early/2014/02/06/01.str.0000442009.06663.48

Syndrome of the trephined

Skin "sinks" weeks to months after a craniectomy.  It can have minor or major presentations, rarely coma, and be relieved with placing patient in trendelenberg position and using a titanium mesh.