Sunday, November 30, 2014

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.

Saturday, November 29, 2014

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

Tuesday, November 25, 2014

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

Friday, November 14, 2014

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

Thursday, November 13, 2014

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