Management of CADASIL Syndrome

Review
Management of CADASIL
syndrome
Expert Opinion on Orphan Drugs Downloaded from informahealthcare.com by Hospital La Paz on 05/09/14
For personal use only.
Michele Ragno & Luigi Trojano

1.
Introduction
2.
Review of evidence
3.
Expert opinion
Division of Neurology, Ospedale Madonna del Soccorso, San Benedetto del Tronto (AP), Italy
Introduction: Cerebral autosomal dominant arteriopathy with subcortical

infarcts and leukoencephalopathy (CADASIL) is the most common hereditary
small-vessel disease. CADASIL is caused by mutations in the NOTCH3 gene
on chromosome 19; its global incidence and prevalence are unknown, likely
because of under-diagnosis. CADASIL is a multisystemic disease, but its main
clinical manifestations are related to the involvement of the brain. Very
few controlled studies have been specifically performed on therapeutic
interventions for CADASIL and its clinical manifestations.
Areas covered: Evidence is reviewed about possible effects of controlling risk
factors for the disease, and about treatment of most common clinical manifestations: migraine, TIA/stroke, psychiatric disturbances and epilepsy, cognitive
impairment and dementia.
Expert opinion: Correction of risk factors, and in particular hypertension,
seems to be mandatory for reducing risk of stroke. Antiplatelet agents in secondary prevention in CADASIL might be recommended for secondary but not
for primary prevention. Antiepileptic drugs seem to be the best choice for
prophylaxis of migraine and MA, when needed. Psychiatric symptoms
should be treated with conventional drugs, after reaching correct clinical
diagnosis. Treatment of cognitive impairment and dementia with cholinesterase inhibitors may be effective on executive functions, but no conclusive data
are available about its usefulness.
Keywords: CADASIL, epilepsy, migraine, migraine with aura, stroke, vascular dementia
Expert Opinion on Orphan Drugs (2013) 1(9):695-703
1.
Introduction
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary small-vessel disease, related
to mutations in the NOTCH3 gene on chromosome 19 [1]. CADASIL is caused by a
systemic arteriopathy involving small arteries, characterized by prominent alterations
of vascular smooth muscle cells (VSMCs) and accretion of pathognomonic granular
osmiophilic material (GOM) in indentations of the VSMCs or in the extracellular
space close to VSMCs [2]. Presence of GOM within the media extends into the
adventitia; thickening of the arterial wall leads to lumen stenosis [2]. These lesions
are commonly localized to the brain, but they have also been found in the spinal
cord and in other organs such as the spleen, heart, skin, liver, muscle, retina, aorta,
carotid arteries and kidney [3].
The disease has been reported in several countries from all continents. Its global
incidence and prevalence are unknown, likely because of underdiagnosis. To date
only Razvi et al. [4] provided an estimated minimum prevalence of genetically proven
CADASIL (1.98 per 100,000 adults) in west Scotland. The neuroimaging picture
may be variable, particularly in early stages, but frequent findings on brain MRI
are [5]: i) multifocal and bilateral areas of increased signal on T2-weighted imaging
or fluid-attenuated inversion recovery (FLAIR) in the deep periventricular white
10.1517/21678707.2013.828998 2013 Informa UK, Ltd. e-ISSN 2167-8707

All rights reserved: reproduction in whole or in part not permitted
695
M. Ragno & L. Trojano
Article highlights.
.
.
.
Cerebral autosomal dominant arteriopathy with

subcortical infarcts and leukoencephalopathy (CADASIL)
is the most common hereditary small-vessel disease; it is
a multisystemic disease, but its main clinical
manifestations are related to the involvement of
the brain.
Very few controlled studies have been specifically
performed on therapeutic interventions for CADASIL
and its clinical manifestations.
Correction of risk factors, and in particular hypertension,
seems to be mandatory for reducing risk of stroke;
antiplatelet agents might be recommended for
secondary but not for primary prevention.
Antiepileptic drugs seem to be the best choice for
prophylaxis of migraine and MA.
Treatment of cognitive impairment and dementia with
cholinesterase inhibitors may be effective on executive
functions, but no conclusive data are available about
its usefulness.
This box summarizes key points contained in the article.
matter of frontal and parietal lobes, in the pons, in the basal

ganglia and most often in the external capsule and the anterior
part of the temporal lobes, sites that are highly suggestive of
CADASIL; ii) focal hypointensities on T1 (lacunar infarcts)
of variable shape, size, and number; iii) lesions suggestive of
microhemorrhages (microbleeds, MBs) detected on gradientecho images (T2*), found in 31 -- 69% of patients and mainly
localized in cortical--subcortical regions, white matter, thalamus and brainstem; likely, MBs and ischemic lesions are manifestations of the same underlying angiopathy, whereas large
intracerebral hemorrhages have been rarely described [6].
MRI changes precede onset of other symptoms by
10 -- 15 years and increase with age: typically MRI abnormalities appear at a mean age of 30 years, and are present in all
individuals carrying the mutation after age of 35 years [2].
Clinical manifestations of CADASIL are strikingly variable
too. They can include i) recurrent cerebral ischemic episodes
(TIA or stroke), that are the most frequent manifestations,
occurring in 60 -- 85% of patients, at a mean age of 49 years
(range 20 -- 70) [7-9]; ii) progressive cognitive decline, that is
the second most frequent clinical manifestation, although
some symptomatic patients do not show any neuropsychological decline over several years [10]; cognitive impairment with
an insidious onset may precede other disturbances [11], and
it is often characterized by prominent defects of attention
and executive functions [12,13], consistent with the wellknown definition of subcortical small-vessel vascular dementia [14]; iii) migraine, most often migraine with aura (MA),
that is usually the first symptom, with an average age at onset
of 30 years, present in 20 -- 40% of patients with CADASIL (a
proportion five times larger than in general population); frequency of attacks varies in affected individuals, from several
attacks in a month to one in 1 -- 2 years [15,16]; iv) epilepsy
696
in 5 -- 10% of patients [2]; v) psychiatric disorders, a very frequent (20 -- 31%), cardinal feature of the disease [7,8,17];
although most studies included a small number of patients,
and diagnoses were mainly based on history or review of clinical records, depression is the most common psychiatric manifestation, but adjustment disorders, anxiety, bipolar disorders,
olfactory hallucinations, persecutory delusions at onset and
schizophrenia have been also described [18,19]; apathy (absence
of motivation associated with decreased voluntary behavior) is
present in about 40% of patients, independently from
depression [20].
Other uncommon clinical manifestations include i) parkinsonism [21]; ii) acute encephalopathies, including rapid development of reversible coma [7,22,23]; and iii) subclinical
myopathic changes, associated with mitochondrial morphological or functional alterations [24,25], or without evident
mitochondrial changes but with core-like lesions, defined as
areas devoid of histochemical oxidative enzyme staining [26,27].
Since CADASIL is caused by a systemic arteriopathy, it is
not surprising that multiple organs can be affected throughout
the disease course. In fact, some reports are available in the literature about involvement of the kidney [3,27], heart [19,28,29],
eyes [30], or peripheral nerves [31]. It is possible that the multiorgan involvement may influence clinical evolution, prognosis
and treatment options for CADASIL, thus suggesting the
need for a multimodal approach to patient examination [19].
At the moment, there is no treatment of proven efficacy for
CADASIL, either aimed at modifying the disease course or at
treating the main symptoms specifically; only anecdotal
reports about therapeutic management in a few patients are
available, with a few exceptions.
2.
Review of evidence
Control of risk factors

Until now, the main marker of disease progression is ageing,
which can be considered as a nonmodifiable risk factor [8,32].
It has been suggested that gender too might shape clinical
and MRI profiles of CADASIL patients. In a recent study
on 313 CADASIL patients, stroke, apathy, disability during
the course of the disease and brain atrophy were more common among men, whereas MA was more common among
women, at least before menopausal age [16]. This observation
might open the issue of the possible role of ovarian hormones
in CADASIL phenotypic expression, although such data are
in line with those reported in general population [33].
Leaving aside the above nonmodifiable features, in planning possible interventions to modify evolution and prognosis
of a genetically determined disease, such as CADASIL, one
should consider strategies aiming to primary and secondary
prevention of most frequent manifestations.
The influence of environmental and lifestyle factors as possible modifiers of the clinical course has been underlined in a
study on monozygotic CADASIL twins [34], in which it has
been suggested that smoking habit, physical activity and early
2.1
Expert Opinion on Orphan Drugs (2013) 1(9)
Management of CADASIL syndrome
statin treatment might modulate clinical phenotypes. Poor

physical activity and smoking have been reported to be associated with early onset of stroke [22] and with risk for stroke [35].
The use of statins (for correcting hypercholesterolemia, but
also to prevent arterial disease and to increase cerebral blood
flow) [36] might be useful, but no significant change in
hemodynamic parameters has been observed in 24 CADASIL
subjects after 8-week treatment with atorvastatin [37].
Conventional cardiovascular risk factors, that are associated
with an increased risk of sporadic small-vessel disease, might
exacerbate damage to the small cerebral vessels caused by the
NOTCH 3 mutation. In this perspective, since most frequent
symptoms are vascular in nature (e.g., TIAs, strokes), welldefined modifiable risk factors for cerebrovascular diseases
should be addressed as a first step: arterial hypertension, diabetes mellitus, hyperomocysteinemia, smoking, high alcohol consumption, poor physical activity, dietary factors, overweight
and obesity, heart pathologies and hypercholesterolemia.
The role of hypertension in increasing stroke risk has been
reported in a large study on consecutive CADASIL patients
[22], and is in keeping with studies showing that higher blood
pressure is associated with brain volume loss and increased
T2 lesion load on serial MRI examination [38,39]. Further longitudinal studies are necessary to prove causality between
hypertension and stroke in CADASIL; but in the meantime,
it seems wise to treat hypertension and other cardiovascular
risk factors aggressively in patients with CADASIL [22].
It is worth remembering that hypertension, together with
age, might represent a risk factor for intracerebral hemorrhages, although they have been described sporadically in
CADASIL [6]. Most importantly, hypertension significantly
increases the risk for vascular dementia (VaD) in general population [40]; thus it is possible that controlling hypertension
might reduce development of VaD in CADASIL, although
at the moment no specific data are available to endorse this
claim.
Arguments in support of reducing blood pressure in
CADASIL routinely, however, should take into account that
these patients have problems in self-regulatory mechanisms
of cerebral blood flow (CBF). Several studies with SPECT,
PET or MRI bolus tracking methods have shown an early
decrease in CBF and cortical metabolism in CADASIL
patients, likely arising from both structural and functional
changes in brain arteries, with an increasing risk for chronic
subcortical ischemia [2,41,42]. Therefore, antihypertensive treatment in CADASIL seems to be potentially useful but great
care should be taken to avoid excessive blood pressure
decrease, and to reduce the putative risk of worsening chronic
hypoperfusion, although no data are available at the moment.
Migraine
As briefly recalled earlier, often migraine, and particularly
MA, is the presenting manifestation of CADASIL in the second or third decade of life [2], with prevalence as high as
75 -- 77% [22,35]. However, migraine and MA are not the
2.2
most disabling symptom in CADASIL and rarely require

prophylactic treatment, as frequency of attacks is low in
most patients. For instance, Gunda et al. [16] reported that
frequency of MA attacks is higher than one in a month only
in 21% of their sample; whereas in the remaining patients,
frequency of attacks ranged from less than one in a month
to one every other year.
It has been suggested that vasoconstrictors such as
ergot derivatives and triptans should be avoided in acute treatment of migraine in CADASIL, whereas conventional analgesics and nonsteroidal anti-inflammatory drugs should be
preferred [43]. In fact, in a case study on a CADASIL patient,
it has been claimed that repeated intake of sumatriptan may
have exacerbated or even caused status migrainosus and persistent aura without infarction [44]. This consideration is in line
with established clinical practice avoiding use of vasoconstrictors in patients with cerebrovascular disease. When prophylactic treatment is needed, conventional drugs such as
antiepileptics or b blockers can be used, but acetazolamide
deserves special attention. Two case reports [45,46] and a retrospective analysis of 32 CADASIL patients with migraine
(11 with and 21 without aura) [47] suggested that acetazolamide can be considered as an effective option for migraine
in CADASIL. Acetazolamide increases cerebral perfusion
through vasodilation both in normal subjects and in CADASIL patients [48-51], and might exert favorable effects on
migraine deriving from cerebral oligoemia [47,52,53]. To date,
cortical oligoemia has been demonstrated only in 1 asymptomatic patient, but it might trigger MA in affected subjects;
the resulting CBF decrease might be relieved by acetazolamide
treatment [41]. Alternatively, the therapeutic mechanism of
acetazolamide could be related to its effects in some familial
ion channels disorders, such as familial hemiplegic migraine,
hypokalemic periodic paralysis and episodic ataxia type 2
[54-56], provided that migraine is a possible disorder of neuronal ion channels [57]. The small number of CADASIL patients
treated with acetazolamide does not allow drawing definite
conclusions about its use, efficacy and safety in CADASIL
migraine. Appropriately sized randomized, double-blind, trials are necessary for this purpose.
Only 1 study demonstrated that homocysteine levels are
associated with an increased risk of migraine and with earlier
age of onset of migraine [34]. On this basis, it is possible to
consider lowering homocysteine blood levels by means of folic
acid and B vitamins [58].
Several CADASIL patients may show atypical migraine
attacks with basilar, hemiplegic, or prolonged aura, or status
migrainosus [44] and acute confusional migraine [59]. AdibSamii et al. [22] suggested that an acute reversible encephalopathy followed by full recovery, the so-called CADASIL
coma [7,23,35], might represent part of the CADASIL migraine
spectrum, since all affected individuals also showed a history
of MA, and in most of them CADASIL coma followed a
typical MA attack. It should also be considered that clinical
presentation of CADASIL coma has some similarities to
697
migraine coma described in familial hemiplegic migraine [60].

Pathogenetic mechanisms capable of explaining the association
of MA with CADASIL coma are unknown. EikermannHaerter et al. [61] reported that NOTCH3 mutations in
CADASIL transgenic mice enhance cortical susceptibility to
spreading depression, the electrophysiological substrate of
MA. Enhanced cortical susceptibility to spreading depression
might explain more frequent and severe MA phenotype in
CADASIL patients (atypical attacks, e.g., coma). The mechanisms linking vascular abnormalities to enhanced cortical
spreading depression susceptibility in CADASIL, however,
are not clear. It is worth mentioning that in two CADASIL
patients with acute complex migrainous episodes, lorazepam
and i.v. mannitol or i.v. sodium valproate were effective therapeutic options [44,62]. It should be taken into account that
both patients had shown previous epileptic seizures, as most
patients with CADASIL coma (some of them treated with
antiepileptic drugs such as i.v. phenytoin), and that epileptic
seizure might have been triggered by migraine (ICHD-2
1.5.5 migraine-triggered seizure).
Psychiatric disturbances and epilepsy

As recalled earlier, several studies have reported psychiatric
disorders, particularly mood disorders, in CADASIL patients.
However, in most cases generic descriptors have been used
without reaching a formal diagnosis according to standardized
criteria. Only a formalized approach will allow establishing
the best therapeutic choice for these aspects.
It is possible to argue that mood disorders in CADASIL
are likely related to the concept of vascular depression.
Increased prevalence of deep white matter hyperintensities
(DWMHs) has been consistently observed in patients with
geriatric depression and bipolar disorder [63]. DWMHs,
which are thought to be ischemic in etiology, may be related
to pathophysiology of mood disorders in the elderly, reasonably because of damage to the cortical--subcortical circuits.
Moreover, ischemic subcortical lesions are appraised as an
important risk factor for mood disorders [64]. Therefore, it is
possible that mood depression in CADASIL is related to subcortical ischemic lesions, although this hypothesis should be
specifically tested.
Within this perspective, it should be mentioned that
valproate is an anticonvulsant drug extensively used in the
treatment of both epilepsy and mood disorders [65,66]. Indeed,
Yuan et al. [67] suggested that valproate might have beneficial
effects in CADASIL via cytoprotective effects on VSMCs,
thus suggesting that valproate might be considered as a novel
therapeutic agent for depression and other disorders (seizures,
CADASIL coma) in CADASIL, although no specific trials
have been conducted.
As regards treatment of epilepsy (that is, recurrent seizures)
in CADASIL, the same principles apply as for psychiatric disorders: at the moment only anecdotal data are available, without specific therapeutic indications but those relative to usual
2.3
698
antiepileptic drugs, that is, treatment should be specifically

tailored to the type of clinical presentation of seizures [8,19,43].
Seizures/epilepsy in CADASIL can be considered as an
instance of poststroke seizures/epilepsy. Stroke is a frequent
cause of epilepsy in adults: frequency of poststroke seizures
ranges 2.3 -- 43% [68]. After a major stroke, most often partial
(motor) seizures with secondary generalization occur
(15 -- 21%) [69]. Seizures are less frequent after lacunar infarcts
(1 -- 3.7%) [70]; however, a higher incidence of seizures (strokerelated-symptoms and seizures: 24.2%) has been reported in a
recent retrospective study on 223 patients affected by cerebral
microangiopathy or cerebral small-vessel disease, possibly
because near-cortex lacunar infarcts may damage U-fibers,
leading to a high propensity for seizures [71].
European guidelines recommend the use of traditional
antiepileptic drugs in presence of recurrent post-stroke seizures [72], but paying particular attention to pharmacological
interactions and side effects, particularly on cognition. For
these reasons, phenobarbital should be avoided, whereas there
are positive indications about efficacy of lamotrigine and
carbamazepine [73], gabapentin [74], sodium valproate [75]
and levetiracetam [76,77] in poststroke partial and generalized
tonic--clonic seizures. By analogy, if seizures/epilepsy in
CADASIL can be encompassed within manifestations of poststroke seizures/epilepsy, the same anticonvulsant drugs as
above, at the same doses, should be considered in CADASIL
as well. However, no anticonvulsant agent has been identified
to be clearly superior for treatment of either acute poststroke
seizures or epilepsy, in general population and in CADASIL.
Future intervention studies should provide precise information about features of CADASIL seizures, including details
about lesion type, site and distribution, about clinical manifestations and about associated risk factors (e.g., gender, age).
TIA/stroke
Patients with TIAs or ischemic stroke have a high risk of
recurrent stroke. Antiplatelet therapy proved to be effective
in secondary stroke prevention and is recommended by wellestablished practice guidelines: in patients without cardiac
source of embolism aspirin, clopidogrel or the combination
of aspirin and dipyridamole is recommended [78-80].
Small subcortical brain infarcts or lacunar strokes in most
cases result from intrinsic disease of the small penetrating
arteries and aspirin is accepted as the standard antiplatelet
therapy for secondary prevention of lacunar stroke, as
detected by MRI [79]. A recent trial on Secondary Prevention
of Small Subcortical Strokes (SPS3) in 3020 patients with
recent symptomatic subcortical lacunar ischemic strokes identified by MRI showed that adding clopidogrel to aspirin did
not reduce the risk of recurrent stroke, but significantly
increased risk of major bleeding complications [81].
It is plausible that these guidelines for treatment of stroke
and lacunar infarcts in general population might apply to
CADASIL too. However, since only a few patients are
included in interventional studies, at the moment treatment
2.4
of TIA/stroke in CADASIL is only empirically based on

usual preventive measures for noncardioembolic ischemic
stroke: use of antiplatelet drugs.
Use of antiplatelet drugs can increase risk for microbleedings such as those identified in gradient-echo MRI in some
CADASIL patients, with increased risk for cerebral hemorrhage. It remains to be clarified whether presence of MBs,
their number and localization, might be useful in evaluation
of hemorrhagic risk. Also in this sense, novel randomized
multicentre controlled trials in CADASIL appear to be necessary, including a sufficient number of CADASIL subjects; the
estimated number of patients for an interventional twoyear study may be in the range of 650 patients [37]. In the
future, use of neurobiological markers of early injury, signalling onset and progression of clinical changes, might help
reducing the number of patients needed in therapeutic trials.
The search for these markers in MR studies (e.g., progression
of atrophy, accumulation of white matter lesions and other
typical structural changes) is under way, as well as analyses
of diffusion histograms and metabolic relations as assessed
by spectroscopy [38,39,82].
2.5
Cognitive impairment
Cognitive impairment and dementia are among the most

frequent manifestation of CADASIL. As stated above,
impairment of executive functions and attention can be found
in patients before development of clinically relevant dementia,
associated with loss of motivation (apathy) [20]. This pattern is
in line with the model of subcortical dementias [14], and in
particular of pure subcortical ischemic vascular dementia [83].
Nonetheless, phenotypic variability of cognitive impairment
and of its progression in CADASIL is wide. It has been suggested that several factors may contribute to this variability,
among which the so-called cognitive reserve [84]. Cognitive
reserve can be considered as the individual threshold for the
amount of brain damage a person can sustain, and can result
from availability of compensatory mechanisms, such as more
flexible use of existing networks or recruitment of additional
networks [84]. This concept has been proposed for patients
with Alzheimers disease, mild cognitive impairment and
healthy aging, but a recent study on 313 patients extended
validity of this concept to CADASIL and, by implication, to
vascular dementia [85]. The authors found that education
(that is considered as a valid proxy for cognitive reserve) had
an independent impact on measures of cognitive speed in subjects with mild to moderate degree of brain pathology,
whereas there was no significant influence of education on
cognition in patients with severe MRI changes [85]. The phenotypic expression of cognitive decline in CADASIL must
thus be considered as due to the interaction between individual features and biologically-determined lesions, expressed as
total lesion load [86], particularly in hippocampal regions [87].
It has been suggested that subcortical ischemic lesions
determine cognitive impairments by disrupting cholinergic
afferents to the neocortex [88-90]. This hypothesis led to
promoting a multicentre, placebo-controlled randomized

double-blind trial to assess the possible effect of cholinesterase
inhibitors in CADASIL [91], although contrasting data about
the effects of these drugs in VaD have been reported so
far [92]. Administration of 10 mg donepezil for 18 weeks to
a cohort of CADASIL patients with moderate to severe cognitive impairment had no effect on the primary endpoint, a
global measure of cognitive impairment, but determined
selective improvements on measures of executive functions [91].
Such findings are not conclusive, and the study itself has some
limitations [93], but further controlled studies are warranted to
explore this crucial issue. It has also to be taken into account
that unknown factors might condition response to cholinesterase inhibitors, as it has been demonstrated in VaD [94]. It
is also possible that other cholinesterase inhibitors, such as
galantamine, may be more effective than donepezil, but until
now only anecdotal evidence is available [95].
3.
Expert opinion
Before suggesting a treatment algorithm, some issues have to

be underlined. First, CADASIL is a multisystemic disease,
with preferential involvement of the brain, but at the moment
mechanisms underlying stroke, MA, mood disorders and vascular cognitive impairment are far from being understood.
Second, there is a wide variability in the natural history of
CADASIL not only among different genotypic variants but
also among individuals from the same pedigree. Moreover,
mild cognitive impairments, particularly in executive domains
can be found in asymptomatic individuals.
All CADASIL symptoms, particularly migraine and
psychiatric disorders, should be defined according to current
diagnostic criteria, and motor and cognitive conditions should
be monitored by means of standardized tests to follow the disease course over time. For instance, cognitive screening instruments specifically targeted to assess executive function might
be used in longitudinal studies to monitor cognitive aspects
related to progression of subcortical ischemic VaD; such tools
might reveal particularly important for future intervention trials. However, it has been recently suggested that clinical severity in subjects with CADASIL might be best expressed and
monitored by means of specific and global neurological scales,
including assessment of motor, gait and cognitive aspects [96].
Surrogate markers might be provided by quantitative MRI
measures, including lesion volume [97], brain atrophy rates [98],
number of new ischemic lesions [99], and diffusion tensor
imaging measures [38,39,82]. All these issues should be tackled
with in planning future multicenter intervention trials,
recruiting patients in different disease stages.
Which treatment can be considered optimal for CADASIL
management in 2013?
As a first step, the correction of risk factors seems to be
mandatory for reducing stroke risk. In particular, treating systolic and diastolic hypertension seems to be necessary in all
699
hypertensive CADASIL patients, to the aim of keeping mean

systolic blood pressure values within 90 -- 140 mmHg.
The use of antiplatelet agents in secondary prevention in
CADASIL might be recommended for secondary prevention
and not for primary prevention.
Antiepileptic drugs seem to be the best choice for prophylaxis of migraine and MA.
Psychiatric symptoms should be treated with conventional
drugs, after reaching correct clinical diagnosis.
Treatment of cognitive impairment and dementia with
cholinesterase inhibitors has been demonstrated to be of limited short-term efficacy on executive functions, but no conclusive data are available about its clinical usefulness.
It must be underlined, however, that only a few studies have
been performed to specifically evaluate efficacy of the above
treatments in modifying the disease course of CADASIL, or
in managing its main symptoms. Availability of effective therapeutic options will also change perspectives of genetic testing,
that at the moment is limited by considerations about its lack
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Affiliation
Michele Ragno1 MD & Luigi Trojano*2,3 MD

*,
Authors for correspondence
1
Division of Neurology, Ospedale Madonna del
Soccorso, San Benedetto del Tronto (AP), Italy
E-mail: michele.ragno@sanita.marche.it
2
Second University of Naples,
Department of Psychology, Caserta, Italy
Tel: +39 0823 274774;
Fax: +39 0823 274774;
luigi.trojano@unina2.it
3
Rehabilitation Institute of Telese Terme,
Salvatore Maugeri Foundation, IRCCS, Telese
Terme (BN), Italy
703

Management of CADASIL Syndrome

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Management of CADASIL Syndrome

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Review

Michele Ragno & Luigi Trojano

Introduction: Cerebral autosomal dominant arteriopathy with subcortical

10.1517/21678707.2013.828998 2013 Informa UK, Ltd. e-ISSN 2167-8707

M. Ragno & L. Trojano

Cerebral autosomal dominant arteriopathy with

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matter of frontal and parietal lobes, in the pons, in the basal

Control of risk factors

Expert Opinion on Orphan Drugs (2013) 1(9)