Recent Advances in Neurology Difficult Cases
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- Ethelbert Walton
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1 Patient X: History Part 1 Recent Advances in Neurology Difficult Cases Heather J. Fullerton, MD, MAS Professor of Neurology & Pediatrics Director, Pediatric Brain Center Previously healthy 14-year old boy While playing basketball with friends, he had a witnessed convulsion lasting six minutes. Afterwards he had a mild headache and rightsided weakness. He was transported by EMS to a hospital where he was found to be aphasic with a right hemiparesis. 2 Q1: True or false? A child with a seizure followed by hemiparesis can be observed without emergent brain imaging because the hemiparesis is most likely a Todd s. A. True B. False T r u e 8% 92% F a l s e DDX for acute hemiparesis in a child Migraine Seizure (Post-ictal Todd s) Stroke/TIA Brain tumor Super rare things: mitochondrial disorders (MELAS), channelopathies (alternating hemiplegia of childhood) Very hard to distinguish clinically because seizure and headache common in children with acute stroke A child with first-ever acute hemiparesis needs urgent brain imaging to rule out stroke even if preceding seizure or headache 3 4 1
2 Stroke does occur in Children: Half of strokes in kids are hemorrhagic Incidence: 4.6 per 100,000 children/year in US 1 per 3,500 neonates Children Adults About 5,000 US kids/year Ischemic Hemorrhagic Hemorrhagic Ischemic Agrawal, Stroke, 2009 Broderick, J Child Neuro, 1993 Approach to Imaging for Suspected Stroke Emergent MRI with DWI/ADC Followed by immediate brain MRA if + infarct Especially if within 6 hour thrombectomy window More thorough vascular imaging later Approach to Imaging What about CT/CTA? Use sparingly: radiation more concerning in young kids Useful if MR can t be done (pacer leads) or can t be done quickly & thrombectomy would be considered Sensitive for hemorrhage, not acute infarct Don t add CT perfusion (not worth the radiation) 10 hr old infarct in 5 month old with congenital heart dz 2
3 Patient X: History Part 2 Back to our 14 year old boy with a convulsion followed by right hemiparesis and aphasia Emergent MRI: small infarcts of L MCA territory MRA: mild narrowing of his left supraclinoid internal carotid artery (ICA) thrombus versus arteriopathy? Q2: What is the most common cause of arterial ischemic stroke in a previously healthy child? A. Embolism from congenital heart disease B. Embolism from endocarditis C. Sickle cell disease D. Genetic thrombophilia E. Arteriopathy 34% 5% 17% 2% 41% E m b o l i s m f r o m c o n g e n i t a... E m b o l i s m f r o m e n d o c a r d i t i s S i c k l e c e l l d i s e a s e G e n e t i c t h r o m b o p h i l i a A r t e r i o p a t h y 9 10 Arteriopathy (disease of a cervical or cerebral vessel) is the most common cause of childhood arterial ischemic stroke. And the strongest predictor of recurrent stroke. Kids with arteriopathy are at highest risk of recurrence Proportion recurrent stroke free Time from index AIS to first recurrent stroke, months Idiopathic Cardioembolic Almost 1 in 4 Fullerton, Stroke, 2015 Possible arteriopathy Definite arteriopathy 11 3
4 Patient X: History Part 3 MRA on transfer Admitted to the hospital and placed on IV heparin. An echocardiogram was normal. His deficits improved dramatically over the next few days. 3-days post stroke: severe left frontal headache. 4-days post-stroke: agitated with worsened aphasia and right hemiparesis. His deficits were positional, improving when placed flat, and responded to IV hydration and pressors. Repeat MRI/A: new infarction in the left MCA territory and severe narrowing of his left distal ICA and proximal MCA. Transferred to UCSF Q3: What causes rapidly progressive stenosis of the distal ICA in children? A. Focal Cerebral Arteriopathy Inflammatory (FCA-i), also known as Transient Cerebral Arteriopathy (TCA) B. Moyamoya disease (idiopathic moyamoya) C. Moyamoya syndrome (secondary moyamoya) 62% D. Kawasaki disease FCAi Lenticulostriate infarcts Beading of M1 on conventional angiography 18% 5% 14% F o c a l C e r e b r a l A r t e r i o p... M o y a m o y a d i s e a s e ( i d i o... M o y a m o y a s y n d r o m e ( s... K a w a s a k i d i s e a s e
5 Natural History of FCA-i What causes FCA-i? Monophasic disease Initial progression Nonprogression after 6 months Improvement or stabilization; rarely normalization Chabrier & Sebire, J Child Neurol 1998; Danchaivijitr, Ann Neurol 2006 Acute 2 months 12 months Varicella zoster virus (VZV) strong evidence from histopathology studies Other herpesviruses, like herpes simplex virus, type 1 (HSV-1) evidence from case reports and a prospective casecontrol study (Vascular effects of Infection in Pediatric Stroke, VIPS study) Other pathogens? Abnormal host immune response? Courtesy of G. DeVeber 18 Q4: What are proven therapies for FCAi? A. Aspirin B. Revascularization Surgery (STA-MCA bypass) C. Acyclovir D. Corticosteroids E. None of the above A s p i r i n 18% R e v a s c u l a r i z a t i o n S u r g e r y... 9% A c y c l o v i r 13% C o r t i c o s t e r o i d s 23% N o n e o f t h e a b o v e 37% Patient X: History Part 4 Admitted to the PICU, placed on IVF (1.5 x maintenance), head of bed flat, on IV pressors Had flow-dependent deficits: when upright, hemiparesis worsened Serologies positive for HSV-1 After several days of observation, with no improvement in flowdependent deficits, treated with IV corticosteroids and acylovir After several days, patient stabilized Slowly weaned off IVF and pressors 2 month follow-up: dramatic improvement in ICA stenosis 2 year follow-up: no further strokes
6 Follow-up MRA Before his arteriopathy progressed, could we have diagnosed him with FCAi? FCA differential diagnosis: FCAi FCAd (focal cerebral arteriopathy, dissection subtype) Intracranial dissection Can also show early progression (spiral dissection) Difficult to distinguish from FCAi Vessel Wall Imaging (VWI) can help Early, unilateral moyamoya Lenticulostriate collaterals Chronic, silent infarcts Enhancement on VWI: suggests FCAi Moyamoya disease/syndrome Slow narrowing of bilateral supraclinoid ICAs 2ary lenticulostriate collaterals Can be unilateral at onset Secondary form: sickle cell disease, Down syndrome, NF-1, cranial radiation for cancer Courtesy of Max Wintermark, MD 6
7 Childhood arteriopathy diagnosis important for management and prevention of recurrent stroke Aspirin Heparin Revascularization Surgery (EDAS, STA-MCA bypass) Activity Restriction Hydration & BP augmentation FCAi x Rarely Acutely Dissection x Sometimes Lifelong Moyamoya x Routinely Long term Clinical trials planned for corticosteroids and acyclovir for FCAi. P.S. FCAi has also been reported in young adults 25 7
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