CADASIL

[MIM 125 310]

Acronym for Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. 

Non-atheromatous arterial disease (granular deposits in the arteriolar walls) resulting in subcortical infarction and lesions of the cerebral white matter). Autosomal dominant transmission of mutations in the Notch3 receiver gene (19p.13.2-p13.1) (a locus nearby the calcium channel CACNL1A4, mutations of which cause familial hemiplegic migraine). It generally starts during from the third decade with atypical migraines with aura without headache, or migraines with hemiplegia, epilepsy and early dementia. A history of migraines in childhood is often found.

It seems that the pathology is caused by cerebral hypoperfusion reaching primarily the white matter and the subcortical regions. The  cerebrovascular response to changes in paCO2 could be reduced but cerebral autoregulation seems to be preserved at least in the early stages of the disease.

Diagnosis: genetics, skin biopsy. 

Evolution: gradual worsening of dementia. Increased risk of sudden death from cardiac cause partly associated with a reduction in the variability of heart rate, a sign of cardiac autonomic dysfunction.

Treatment:   low-dose aspirin; antiepileptic drugs for epilepsy; sometimes acetazolamide (carbonic anhydrase inhibitor).


Anesthetic implications:

dementia, epilepsy; aim at maintaining cerebral perfusion pressure within the patient's normal range: avoid hypo - and hypercapnia as well as hypo - and hypertension. It is probably useful to use NIRS to assess cerebral oxygenation (cortical) and quickly detect hypoperfusion in the monitored area (by comparison to the values obtained before induction of anesthesia). Monitoring the depth of anesthesia (BIS for example) is useful to avoid awareness and titrate depth of hypnosis; in case of dementia, it is useful to know the awake BIS value measured before induction of anesthesia.


References : 

-        Cleves C, Friedman NR, Rothner AD, Hussain MS. 
Genetically confirmed CADASIl in a pediatric patient
Pediatrics 2010; 126: e 1603-7.

-        Dieu JH, Veyckemans F. 
Perioperative management of a CADASIL type arteriopathy patient.  
Br J Anaesth 2003 ; 91: 442-4.

-        Pfefferkorn T, von Struckrad-Barre S, Herzog J, Gasser T, Hamann GF, Dichgans M.
Reduced cerebrovascular CO2 reactivity in CADASIL: a transcranial Doppler sonography study. 
Stroke 2001; 32: 17-21.

-         Singhal S, Markus HS. 
Cerebral reactivity and dynamic autoregulation in nondemented patients with CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). 
J Neurol 2005; 252: 163-7.

-         Rufa A, Guideri F, Acampa M, Cevenini G et al. 
Cardiac autonomic nervous system and risk of arrhythmias in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). 
Stroke 2007; 38: 276-80.

-         Lamberg JJ, Cherian VT. 
Neuraxial anesthesia in CADASIL syndrome. 
J Neurosurg Anesthesiol 2013; 25: 216.


Updated: November 2019