Open Access

Diagnostic criteria for CADASIL in the International Classification of Headache Disorders (ICHD-II): are they appropriate?

The Journal of Headache and Pain201011:203

https://doi.org/10.1007/s10194-010-0203-6

Received: 13 December 2009

Accepted: 16 February 2010

Published: 12 March 2010

Abstract

We reviewed the characteristics of headache in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), to verify the appropriateness of the International Classification of Headache Disorders, second edition (ICHD-II) criteria. Available data were found through Medline/PubMed using the keyword “cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)”. The search was restricted to studies published in English in the years between 1993 and 2008. We excluded studies that did not report original data on CADASIL and information regarding the presence of headache. We found 34 studies reporting data on 749 patients overall; 387 (51.7%) patients had headache. According to the authors’ definition, 356 (92%) patients were reported as having migraine and 31 (8%) as having headache. Of the 356 patients who were defined as migraineurs, 125 (35.1%) had migraine with aura, 7 (2%) migraine without aura, 156 (43.8%) unspecified migraine and 68 (19.1%) had more than one type of migraine. Among the 31 patients reported as suffering from headache, the headache was not further detailed in 18 (58.1%) patients; it was defined as chronic in 6 (19.3%), as resembling migraine with aura in 4 (12.9%), as resembling migraine without aura in 2 (6.5%) and as tension type in 1 (3.2%) patient. In patients with CADASIL, the headache was usually referred to as migraine and mostly as migraine with aura. However, this referral is formally incorrect since the diagnostic criteria for any type of migraine in the ICHD-II require that the disturbance is not attributed to another disorder. For this reason, we suggest updating the ICHD-II in relation to CADASIL. Our suggestion is to insert a new category referred to as Headache attributed to genetic disorder including Headache attributed to CADASIL.

Keywords

MigraineHeadacheCADASILInternational Classification of Headache Disorders

Introduction

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset inherited disease due to mutations in the Notch3 gene on chromosome 19p13 [13]. These mutations cause an abnormal accumulation of Notch3 in the cytoplasmic membrane of vascular smooth muscle cells both in cerebral and extracerebral vessels, which appear as granular osmiophilic deposits on electron microscopy [4]. The neuroradiological hallmark of the disease is represented by leukoencephalopathy with lacunaes in the basal ganglia, which can become evident at any stage of the disease [4]. The clinical spectrum of CADASIL includes migraine with or without aura, mood disturbances, transient ischemic attacks or strokes (usually lacunar infarcts) and progressive cognitive decline [1, 2, 4, 5]. Other disturbances are also reported, including epilepsy, acute reversible encephalopathy and myopathy [6, 7].

Headache in patients with CADASIL was first coded, according to the Classification and Diagnostic Criteria for Headache Disorders, Cranial Neuralgias and Facial Pain (ICHD), among headaches associated with other vascular disorders (code 6.9) [8]. Following the ICHD, second edition (ICHD-II), headache in patients with CADASIL is coded among the headaches attributed to cranial or cervical vascular disorder (code 6.7.1) on the implicit assumption that a vascular disorder is the cause of the headache [9], an interpretation that, in our opinion, should be reconsidered [5, 10].

To verify the appropriateness of the ICHD-II criteria, we deemed it to be of interest to review the studies reporting any headache in patients with CADASIL.

Methods

Available data for this review were found through Medline/PubMed using the keyword “cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)”. For our study, we reviewed all studies published in English between 1993 and 2008. All the retrieved studies were examined by the two of us (SS and DD). We excluded studies that did not report original data on CADASIL such as reviews, meta-analyses, comments and editorials. Among studies describing clinical details of patients with CADASIL, we excluded those in which there was no mention of headache or migraine. To exclude overlapping of CADASIL cases by the same research group, we considered what authors wrote in their studies and, where necessary, contacted the corresponding author.

Two of us (SS and DD) evaluated and classified all the reported cases separately. Any possible disagreement was resolved by a third opinion (AC). We maintained the terminology used by the authors in their studies and, consequently, where authors classified the headache according to the ICHD-II we kept their classification and where they used terms not contemplated in the ICHD or ICHD-II we kept their terminology. We also considered whether the headache was the first symptom or whether it was preceded by an ischemic stroke, TIA or other symptoms such as cognitive and psychiatric disturbances.

Mean age ± standard deviation (SD) was calculated with the method of weighted mean.

Results

The Medline/PubMed search identified 590 studies; 508 studies were excluded because they did not report clinical data or because there was no mention of headache, and 48 because their data had been already included in other studies by the same authors. We finally reviewed 34 (5.8%) studies including 16 case reports or letters (Table 1) [1, 57, 1140].
Table 1

Studies included in the review

First author

Year of publication

Publication type

Included patients (n)

Patients with any headache (n)

Arboleda

2002

OR

7

7

Bergmann

1996

OR

10

5

Bohlega

2007

OR

19

7

Brulin

2002

OR

50

32

Ceroni

2000

OR

8

6

Chabriat

1995

OR

45

10

Choi

2006

OR

20

6

Coto

2006

CR

1

1

Dichgans

1998

OR

102

48

Engelter

2002

CR

1

1

Finnilà

2001

CR

1

1

Hutchinson

1995

OR

10

6

Iwatsuki

2001

CR

3

1

Jung

1995

OR

10

3

Kim

2006

OR

5

1

Malandrini

2006

OR

14

4

Mandellos

2005

CR

4

1

Markus

2002

OR

83

31

Mellies

1998

CR

6

5

Pantoni

2004

CR

3

3

Peters

2004

OR

80

27

Ragno

2006

CR

6

1

Razvi

2005

OR

40

26

Rubio

1997

CR

3

3

Rufa

2004

CR

1

1

Sacco

2008

CR

1

1

Schon

2003

CR

6

6

Singhal

2005

OR

112

84

Saskia

2003

CR

6

3

Sullivan

1997

CR

5

2

Valko

2007

CR

1

1

Vahedi

2004

OR

72

41

Vérin

1995

OR

13

11

Williamson

1999

CR

1

1

OR original research, CR case report

The reviewed studies provided data on 749 patients including 387 (51.7%) who had headache. According to the authors’ definition, 356 (92%) patients were reported as having migraine and 31 (8%) as having headache (Table 2).
Table 2

Overall characteristics of patients with CADASIL

Characteristics

Migraine

Headache

Patients (n)

356

31

Gendera (%)

 Men

36.7

36.4

 Women

63.3

63.6

Mean age at onset (years)

32.2

38.9

aWhere available

Out of the 356 patients described as migraineurs, 125 (35.1%) had migraine with aura, 7 (2%) migraine without aura, 156 (43.8%) unspecified migraine, and 68 (19.1%) had more than one type of migraine (Table 3). Among the 125 patients who had migraine with aura, 24 (19.2%) had migraine with typical aura, 7 (5.6%) migraine with prolonged aura, 5 (4.0%) familial hemiplegic migraine, 2 (1.6%) basilar migraine, while in 87 (69.6%) patients the migraine type was not reported. The aura was visual in 10 (8%) patients, sensory in 7 (5.6%), motor in 5 (4%) and included multiple symptoms in 25 (20%); the aura type was not specified in 78 (62.4%) patients. Among the 68 patients with more than one type of migraine, 50 (73.5%) had migraine with aura, 38 (55.9%) migraine without aura, 18 (26.5%) migraine with aura and without headache, 13 (19.1%) basilar migraine, 11 (16.2%) familial hemiplegic migraine, 11 (16.2%) migraine with unspecified atypical aura, 4 (5.9%) acute onset aura without headache, 2 (2.9%) unspecified migraine, 1 (1.5%) migraine with prolonged aura, 1 (1.5%) migraine with acute onset aura, and 1 (1.5%) had status migrainosus (Table 3). At the onset of migraine, the mean age ± SD was 32.2 ± 13.1 years.
Table 3

Distribution of migraine subtypes in patients with CADASIL

Migraine subtype

ICHD code

ICHD-II code

Patients

n

%

Migraine without aura

1.1

1.1

7

2.0

Migraine with aura

1.2

1.2

125

35.1

 Migraine with typical auraa

1.2.1

1.2.1

24

 

 Migraine with prolonged aura

1.2.2

7

 

 Familial hemiplegic migraine

1.2.3

1.2.4

5

 

 Basilar migraine

1.2.4

1.2.6

2

 

 Unspecified

87

 

Unspecified migrainec

156

43.8

More than one type of migraine

68

19.1

 Migraine with aurab

1.2

1.2

50

 

 Migraine without aura

1.1

1.1

38

 

 Migraine aura without headache

1.2.3

18

 

 Basilar migraine

1.2.6

13

 

 Familial hemiplegic migraine

1.2.3

1.2.4

11

 

 Migraine with unspecified atypical aura

11

 

 Acute-onset aura without headache

4

 

 Unspecified migrainec

2

 

 Migraine with prolonged aura

1.2.2

1

 

 Migraine with acute-onset aura

1

 

 Status migrainosus

1.5.2

1

 

aIncludes one patient diagnosed with migraine accompagnée23

bIncludes two cases of migraine accompagnée23

cUnspecified migraine includes cases defined as migraine by authors without any further detail

In the 31 patients reported as having headache, the headache was not further specified in 18 (58.1%) patients, was defined as chronic in 6 (19.3%), as resembling migraine with aura in 4 (12.9%), as resembling migraine without aura in 2 (6.5%), and as tension type headache in 1 (3.2%) patient. At the onset of headache, mean age ± SD was 38.9 ± 16.8 years.

We also analyzed whether the headache was the first symptom or whether it was preceded by an ischemic stroke, TIA or by other symptoms. After excluding patients for whom data were not reported, 81 patients were described as suffering from migraine and 19 from headache. While 9 of the 81 patients (11.1%) had a previous stroke or TIA, migraine was the first symptom in 66 patients (81.5%) and in 6 (7.4%) it was preceded by other symptoms. While 3 of the 19 patients (15.8%) had a previous stroke or TIA, headache was the first symptom in 14 (73.7%) and in 2 (10.5%) it was preceded by other symptoms.

Discussion

From the 34 reviewed studies, we collected data on 387 patients [1, 540]. In none of the cases, the headache was coded according to the ICHD [8] or ICHD-II [9] criteria. The ICHD-II diagnostic criteria for Headache attributed to CADASIL required the following: (A) attacks of migraine with aura, with or without other neurological signs; (B) typical white matter changes on magnetic resonance imaging T2-weighted sequences; (C) diagnostic confirmation from skin biopsy evidence or genetic testing (Notch3 mutations) [9]. The coding of headache according to the ICHD or ICHD-II criteria might not have been done due to the paucity of details reported in the previous and present classification. Had authors correctly applied the ICHD-II criteria, patients with CADASIL would have been diagnosed as suffering from headache attributed to CADASIL without any further detail. In the reviewed studies, we found that 51.7% of patients with CADASIL were reported to have suffered from headache. Anyhow, despite that headache represents one of the major clinical features of CADASIL, we cannot exclude that some patients suffered from a primary headache. Besides, based on age of onset and clinical characteristics of the headache in CADASIL resembling those of some primary headaches, it was not possible to establish the proportion of primary headaches in the same patients. The headache in patients with CADASIL was more frequently and clearly defined as migraine and the majority of the migrainous patients were reported as suffering from migraine with aura (35.1%). Formally, this codification was inappropriate since diagnostic criteria for any type of migraine in the ICHD-II require that the disturbance is not attributed to another disorder. If the classification of CADASIL in the ICHD-II was not revised, clinicians will be induced to commit a formal error defining the headache as migraine or omit useful clinical details attributing the headache to CADASIL without giving any further characteristic. As much as 31 cases were diagnosed with disturbance other than migraine; in those cases, the authors used a generic terminology and possibly included patients suffering from primary headaches such as tension-type headache.

The inclusion of headache in CADASIL, in chapter 6 of ICHD-II, among Headache attributed to cranial or cervical vascular disorder, implies that the headache is caused by a vascular disease. This implication may rely on two possibilities: the former is that the headache in CADASIL might be considered secondary to the presence of an organic vascular lesion and the latter is that a disorder of the vascular system might be considered as the common underlying pathogenic mechanism that causes both headache and stroke. Referring to the former possibility, in CADASIL, the headache is usually the first symptom of the disease (73.7–81.5% according to reviewed data) preceding the onset of stroke or TIA. Moreover, a diagnosis of secondary headache is usually evident only when the headache resolves or greatly improves within a specified time interval after its onset or after the acute phase of the vascular disorder; however, this evolution is not reported in patients with CADASIL since the headache persists across the years. Consequently, for all the above reported reasons, this possibility is unlikely. Referring to the latter possibility, we have to consider that the underlying pathology in CADASIL is represented by an angiopathy with a unique type of ultrastructural basal lamina deposits and by degeneration of vascular smooth muscle cells, which are the major source of the Notch3 expression. The evidence for a functional impairment of vascular smooth cells is in line with this latter hypothesis [41] and consequently the pathogenic assumption reported in the ICHD-II is correct. However, we would underscore that the primary mechanism is not represented by the vascular damage, but by the genetic alteration in the Notch3 expression. For all these reasons, we suggest considering the possibility of revising the ICHD-II when referring to CADASIL. Specifically, we suggest adding a new category that could be named Headache attributed to genetic disorder including Headache attributed to CADASIL (Table 4). The new category might include also other genetic diseases in which headache represents a major clinical feature. Moreover, the new category should also report subtypes according to specific clinical details to allow the precise characterization of headache in the single patient (Table 4). The proposed diagnostic criteria for headache attributed to CADASIL are reported in Table 5. If our proposal is shared by the experts in the field, we think that it shall be easier from now on to characterize patients with CADASIL uniformly and that a good step forward will be realized.
Table 4

Proposal for a new classification of headache in patients with CADASIL based on available data

15 Headache attributed to genetic disorder

 15.1 Headache attributed to CADASIL

  15.1.1 Migraine without aura attributed to CADASIL

  15.1.2 Migraine with aura attributed to CADASIL

   15.1.2.1 Typical aura with migraine headache

   15.1.2.2 Typical aura without headache

   15.1.2.3 Hemiplegic migraine

   15.1.2.4 Basilar-type migraine

  15.1.3 Complications of migraine attributed to CADASIL

   15.1.3.1 Status migrainosus

   15.1.3.2 Persistent aura without infarction

  15.1.5 Unspecified headache

 15.2 Headache attributed to other genetic disordersa

aThis category is to be expanded and detailed

Table 5

Proposed diagnostic criteria for the new category of headache attributed to genetic disorder

15.1 Headache attributed to CADASIL

 A. Attacks of headache with or without neurological symptoms

 B. Typical white matter changes on MRI (T2W)

 C. Diagnostic confirmation from skin biopsy evidence or genetic testing (Notch 3 mutations)

15.1.1 Migraine without aura attributed to CADASIL

 A. Attacks of headache fulfilling criteria A–D for 1.1 Migraine without aura

 B. Attributed to CADASIL

15.1.2 Migraine with aura attributed to CADASIL

 A. Attacks of headache fulfilling criteria A and B for 1.2 Migraine with aura

 B. Attributed to CADASIL

15.1.2.1 Typical aura with migraine headache attributed to CADASIL

 A. Attacks of headache fulfilling criteria A–D for 1.2.1 Typical aura with migraine headache

 B. Attributed to CADASIL

15.1.2.2 Typical aura without headache attributed to CADASIL

 A. Attacks of headache fulfilling criteria A–D for 1.2.3 Typical aura without headache

 B. Attributed to CADASIL

15.1.2.3 Hemiplegic migraine attributed to CADASIL

 A. Attacks of headache fulfilling criteria A–C for 1.2.5 Sporadic hemiplegic migraine

 B. Attributed to CADASIL

15.1.2.4 Basilar-type migraine attributed to CADASIL

 A. Attacks of headache fulfilling criteria A–D for 1.2.6 Basilar-type migraine

 B. Attributed to CADASIL

15.1.3.1 Status migrainosus attributed to CADASIL

 A. Attacks of headache fulfilling criteria A and B for 1.5.2 Status migrainosus

 B. Attributed to CADASIL

15.1.3.2 Persistent aura without infarction attributed to CADASIL

 A. Attacks of headache fulfilling criterion A for 1.5.3 Persistent aura without infarction

 B. Attributed to CADASIL

15.1.5 Unspecified headache

 A. Headache is or was present

 B. Not enough information to classify the headache in a patient otherwise diagnosed with CADASIL

Declarations

Conflict of interest

None.

Authors’ Affiliations

(1)
Department of Neurology, University of L’Aquila

References

  1. Chabriat H, Vahedi K, Iba-Zizen MT, Joutel A, Nibbio A, Nagy TG, Krebs MO, Julien J, Dubois B, Ducrocq X, Levasseur M, Homeyer P, Mas JL, Lyon-Caen O, Tournier Lasserve E, Bousser MG (1995) Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Lancet 346:934–939, 10.1016/S0140-6736(95)91557-5, 1:STN:280:DyaK28%2FgsF2qug%3D%3D, 7564728PubMedView ArticleGoogle Scholar
  2. Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, Alamowitch S, Domenga V, Cécillion M, Marechai E, Maciazek J, Vayssiere C, Cruaud C, Cabanis EA, Ruchoux MM, Weissenbach J, Bach JF, Bousser MG, Tournier–Lasserve E (1996) Notch 3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 383:707–710, 10.1038/383707a0, 1:CAS:528:DyaK28XmsVGnsro%3D, 8878478PubMedView ArticleGoogle Scholar
  3. Sacco S, Olivieri L, Bastianello S, Carolei A (2006) Comorbid neuropathologies in migraine. J Headache Pain 7:222–230, 10.1007/s10194-006-0300-8, 16767530PubMed CentralPubMedView ArticleGoogle Scholar
  4. Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG (2009) CADASIL. Lancet Neurol 8:643–653, 10.1016/S1474-4422(09)70127-9, 19539236PubMedView ArticleGoogle Scholar
  5. Vahedi K, Chabriat H, Levy C, Joutel A, Tournier-Lasserve E, Bousser MG (2004) Migraine with aura and brain magnetic resonance imaging abnormalities in patients with CADASIL. Arch Neurol 61:1237–1240, 10.1001/archneur.61.8.1237, 15313840PubMedView ArticleGoogle Scholar
  6. Schon F, Martin RJ, Prevett M, Clough C, Enevoldson TP, Markus HS (2003) “CADASIL coma”: an underdiagnosed acute encephalopathy. J Neurol Neurosurg Psychiatry 74:249–252, 10.1136/jnnp.74.2.249, 1:STN:280:DC%2BD3s%2FisFWlsA%3D%3D, 12531961PubMed CentralPubMedView ArticleGoogle Scholar
  7. Valko PO, Siccoli MM, Schiller A, Wieser HG, Jung HH (2007) Non-convulsive status epilepticus causing focal neurological deficits in CADASIL. J Neurol Neurosurg Psychiatry 78:1287–1289, 10.1136/jnnp.2007.124800, 17940180PubMed CentralPubMedView ArticleGoogle Scholar
  8. Headache Classification Committee of the International Headache Society (1988) Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 8:1–96, 10.1046/j.1468-2982.1988.0801001.xView ArticleGoogle Scholar
  9. Headache Classification Subcommittee of the International Headache Society (2004) The international headache classification of headache disorders, 2nd edn. Cephalalgia 24(Suppl 1):9–160Google Scholar
  10. Sacco S, Carolei A (2007) Migraine attributed to genetic disorder. Funct Neurol 22:117–118, 17637216PubMedGoogle Scholar
  11. Arboleda-Velasquez JF, Lopera F, Lopez E, Frosch MP, Sepulveda-Falla D, Gutierrez JE, Vargas S, Medina M, Martinez de Arrieta C, Lebo RV, Slaugenhaupt SA, Betensky RA, Villegas A, Arcos-Burgos M, Rivera D, Restrepo JC, Kosik KS (2002) C455R notc3 mutation in a Colombian CADASIL kindred with early onset of stroke. Neurology 59:277–279, 1:CAS:528:DC%2BD38Xmt1Sitr4%3D, 12136071PubMedView ArticleGoogle Scholar
  12. Bergman M, Ebke M, Yuan Y, Brück W, Mugler M, Schwendemann G (1996) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL): a morphological study of a German family. Acta Neuropathol 92:341–350, 10.1007/s004010050528View ArticleGoogle Scholar
  13. Bohlega S, Al Shubili A, Alreshaid A, Alkhairallah T, AlSous MW, Farah S, Abu-Amero KK (2007) CADASIL in Arabs: clinical and genetic findings. BMC Med Genet 8:67, 10.1186/1471-2350-8-67, 17996090PubMed CentralPubMedView ArticleGoogle Scholar
  14. Brulin P, Godfraind C, Leteurtre E, Ruchoux MM (2002) Morphometric analysis of ultrastructural vascular changes in CADASIL: analysis of 50 skin biopsy specimens and pathogenetic implications. Acta Neuropathol 104:241–248, 12172909PubMedGoogle Scholar
  15. Ceroni M, Poloni TE, Tonietti S, Fabozzi D, Uggetti C, Frediani F, Simonetti F, Malaspina A, Alimonti D, Celano M, Ferrari M, Carrera P (2000) Migraine with aura and white matter abnormalities: Notch3 mutation. Neurology 54:1869–1871, 1:CAS:528:DC%2BD3cXktVCnu7k%3D, 10802804PubMedView ArticleGoogle Scholar
  16. Choi JC, Kang SY, Kang JH, Park JK (2006) Intracerebral hemorrhages in CADASIL. Neurology 67:2042–2044, 10.1212/01.wnl.0000246601.70918.06, 17135568PubMedView ArticleGoogle Scholar
  17. Coto E, Menéndez M, Navarro R, Garcia-Castro M, Alvarez V (2006) A new de novo Notch3 mutation causing CADASIL. Eur J Neurol 13:628–631, 10.1111/j.1468-1331.2006.01337.x, 1:STN:280:DC%2BD28zotFagtg%3D%3D, 16796587PubMedView ArticleGoogle Scholar
  18. Dichgans M, Mayer M, Uttner I, Brüning R, Müller-Höcker J, Rungger G, Ebke M, Klockgether T, Gasser T (1998) The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann Neurol 44:731–739, 10.1002/ana.410440506, 1:STN:280:DyaK1M%2FjsVagtQ%3D%3D, 9818928PubMedView ArticleGoogle Scholar
  19. Engelter ST, Rueegg S, Kirsch EC, Fluri F, Probst A, Steck AJ, Lyrer PA (2002) CADASIL mimicking primary angiitis of the central nervous system. Arch Neurol 59:1480–1483, 10.1001/archneur.59.9.1480, 12223037PubMedView ArticleGoogle Scholar
  20. Finnilä S, Tuisku S, Herva R (2001) A novel mitochondrial DNA mutation and a mutation in the Notch3 gene in a patient with myopathy and CADASIL. J Mol Med 79:641–647, 10.1007/s001090100268, 11715067PubMedView ArticleGoogle Scholar
  21. Hutchinson M, O’Riordan J, Javed M, Quin E, Macerlaine D, Wilcox T, Parfrey N, Nagy TG, Tournier-Lasserve E (1995) Familial hemiplegic migraine and autosomal dominant arteriopathy with leukoencephalopathy (CADASIL). Ann Neurol 38:817–824, 10.1002/ana.410380517, 1:STN:280:DyaK28%2FnsVWqtg%3D%3D, 7486874PubMedView ArticleGoogle Scholar
  22. Iwatsuki K, Murakami T, Manabe Y, Narai H, Warita H, Hayashi T, Abe K (2001) Two cases of Japanese CADASIL with corpus callosum lesion. Tohoku J Exp Med 195:135–140, 10.1620/tjem.195.135, 1:STN:280:DC%2BD387hsVSntw%3D%3D, 11846209PubMedView ArticleGoogle Scholar
  23. Jung H, Bassetti C, Tournier-Lasserve E, Vahedi K, Arnaboldi M, Arifi VB, Burgunder JM (1995) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a clinicopathological and genetic study of a Swiss family. J Neurol Neurosurg Psychiatry 59:138–143, 10.1136/jnnp.59.2.138, 1:STN:280:DyaK2MzlsFyksA%3D%3D, 7629527PubMed CentralPubMedView ArticleGoogle Scholar
  24. Kim Y, Kim JS, Kim G, No YJ, Yoo HW (2006) Two novel mutations of the NOTCH3 gene in Korean patients with CADASIL. Mutat Res 593:116–120, 1:CAS:528:DC%2BD28XmsFensw%3D%3D, 16256149PubMedView ArticleGoogle Scholar
  25. Lesnik Oberstein SA, van den Boom R, Middelkoop HA, Ferrari MD, Knaap YM, van Houwelingen HC, Breuning MH, van Buchem MA, Haan J (2003) Incipient CADASIL. Arch Neurol 60:707–712, 10.1001/archneur.60.5.707, 12756134PubMedView ArticleGoogle Scholar
  26. Malandrini A, Carrera P, Palmeri S, Cavallaro T, Fabrizi GM, Villanova M, Fattaposta M, Vismara L, Brancolini V, Tanganelli P, Calì A, Morocutti C, Zeviani M, Ferrari M, Guazzi GC (1996) Clinicopathological and genetic studies of two further Italian families with cerebral autosomal dominant arteriopathy. Acta Neuropathol 92:115–122, 10.1007/s004010050498, 1:STN:280:DyaK28vjvFehtw%3D%3D, 8841656PubMedView ArticleGoogle Scholar
  27. Mandellos D, Limbitaki G, Papadimitriou A, Anastasopoulos D (2005) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in a Greek family. Neurol Sci 26:278–281, 10.1007/s10072-005-0472-z, 1:STN:280:DC%2BD2MrhvFGmtg%3D%3D, 16193256PubMedView ArticleGoogle Scholar
  28. Markus HS, Martin RJ, Simpson MA, Dong YB, Ali N, Crosby AH, Powell JF (2002) Diagnostic strategies in CADASIL. Neurology 59:1134–1138, 1:STN:280:DC%2BD38njs1GitQ%3D%3D, 12395806PubMedView ArticleGoogle Scholar
  29. Mellies JK, Bäumer T, Müller JA, Tournier-Lasserve E, Chabriat H, Knobloch O, Hackelöer HJ, Goebel HH, Wetzig L, Haller P (1998) SPECT study of a German CADASIL family. Neurology 50:1715–1721, 1:STN:280:DyaK1c3psFCksQ%3D%3D, 9633716PubMedView ArticleGoogle Scholar
  30. Pantoni L, Sarti C, Pescini F, Bianchi S, Bartolini L, Nencini P, Basile AM, Lamassa M, Kalaria RN, Dotti MT, Federico A, Inzitari D (2004) Thrombophilic risk factors and unusual clinical features in three Italian CADASIL patients. Eur J Neurol 11:782–787, 10.1111/j.1468-1331.2004.00915.x, 1:STN:280:DC%2BD2crltlaqtg%3D%3D, 15525301PubMedView ArticleGoogle Scholar
  31. Peters N, Herzog J, Opherk C, Dichgans M (2004) A two-year clinical follow-up study in 80 CADASIL subjects: progression patterns and implications for clinical trials. Stroke 35:1603–1608, 10.1161/01.STR.0000131546.71733.f1, 15155961PubMedView ArticleGoogle Scholar
  32. Ragno M, Fabrizi GM, Cacchiò G, Scarcella M, Sirocchi G, Selvaggio F, Taioli F, Ferrarini M, Trojano L (2006) Two novel Italian CADASIL families from Central Italy with mutation CGC-TGC at codon 1006 in the exon 19 Notch3 gene. Neurol Sci 27:252–256, 10.1007/s10072-006-0679-7, 1:STN:280:DC%2BD28rmvVOntw%3D%3D, 16998728PubMedView ArticleGoogle Scholar
  33. Razvi SSM, Davidson R, Bone I, Muir KW (2005) Is inadequate family history a barrier to diagnosis in CADASIL? Acta Neurol Scand 112:323–326, 10.1111/j.1600-0404.2005.00495.x, 1:STN:280:DC%2BD2Mrkt12ltg%3D%3D, 16218915PubMedView ArticleGoogle Scholar
  34. Rubio A, Rifkin D, Powers JM, Patel U, Stewart J, Faust P, Goldman JE, Mohr JP, Numaguchi Y, Jensen K (1997) Phenotypic variability of CADASIL and novel morphologic findings. Acta Neuropathol 94:247–254, 10.1007/s004010050700, 1:STN:280:DyaK2svjs1Ohsw%3D%3D, 9292694PubMedView ArticleGoogle Scholar
  35. Rufa A, De Stefano N, Dotti MT, Bianchi S, Sicurelli F, Stromillo ML, D’Aniello B, Federico A (2004) Acute unilateral visual loss as the first symptom of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Arch Neurol 61:577–580, 10.1001/archneur.61.4.577, 15096408PubMedView ArticleGoogle Scholar
  36. Sacco S, Rasura M, Cao M, Bozzao A, Carolei A (2009) CADASIL presenting as status migrainosus and persisting aura without infarction. J Headache Pain 10:51–53, 10.1007/s10194-008-0079-x, 18953486PubMed CentralPubMedView ArticleGoogle Scholar
  37. Singhal S, Rich P, Markus HS (2005) The spatial distribution of MR imaging abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationship to age and clinical features. Am J Neuroradiol 26:2481–2487, 16286388PubMedGoogle Scholar
  38. Sullivan AA, Teh BT, Jeavons S, Schalling M, Silburn P, Larsson C, Boyle R (1997) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. J Clin Neurosci 4:176–180, 10.1016/S0967-5868(97)90070-9, 1:STN:280:DC%2BD1cvmsFCktg%3D%3D, 18638952PubMedView ArticleGoogle Scholar
  39. Vérin M, Rolland Y, Landgraf F, Chabriat H, Bompais B, Michel A, Vahedi K, Martinet JP, Tournier-Lasserve E, Lemaitre MH, Edan G (1995) New phenotype of the cerebral autosomal dominant arteriopathy mapped to chromosome 19: migraine as the prominent clinical feature. J Neurol Neurosurg Psychiatry 59:579–585, 10.1136/jnnp.59.6.579, 7500094PubMed CentralPubMedView ArticleGoogle Scholar
  40. Williamson EE, Chukwudelunzu FE, Meschia JF, Witte RJ, Dickson DW, Cohen MD (1999) Distinguishing primary angiitis of the central nervous system from cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Arthritis Rheum 42:2243–2248, 10.1002/1529-0131(199910)42:10<2243::AID-ANR30>3.0.CO;2-D, 1:STN:280:DyaK1Mvlt1egsw%3D%3D, 10524700PubMedView ArticleGoogle Scholar
  41. Dichgans M (2002) CADASIL: a monogenic condition causing stroke and subcortical vascular dementia. Cerebrovasc Dis 13:37–41, 10.1159/000049148, 1:CAS:528:DC%2BD38XitVygsLg%3D, 11901241PubMedView ArticleGoogle Scholar

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