International Journal of Neuroscience

ISSN: 0020-7454 (Print) 1543-5245 (Online) Journal homepage: http://www.tandfonline.com/loi/ines20

Neurological abnormalities in localized

scleroderma of the face and head: a case series
study for evaluation of imaging findings and
clinical course

Anna Lis-wity, Ligia Brzeziska-Wciso & Hubert Arasiewicz

To cite this article: Anna Lis-wity, Ligia Brzeziska-Wciso & Hubert Arasiewicz (2016):
Neurological abnormalities in localized scleroderma of the face and head: a case series study
for evaluation of imaging findings and clinical course, International Journal of Neuroscience,
DOI: 10.1080/00207454.2016.1244823

To link to this article: http://dx.doi.org/10.1080/00207454.2016.1244823

Accepted author version posted online: 04

Oct 2016.

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Download by: [Cornell University Library] Date: 23 October 2016, At: 15:05
Publisher: Taylor & Francis
Journal: International Journal of Neuroscience
DOI: http://dx.doi.org/10.1080/00207454.2016.1244823

Neurological abnormalities in localized scleroderma of the face and head: a case series study

for evaluation of imaging findings and clinical course

Anna Lis-wity*, Ligia Brzeziska-Wciso, Hubert Arasiewicz

School of Medicine in Katowice, Medical University of Silesia, Chair and Department of

Dermatology, Poland

* Corresponding author: Chair and Department of Dermatology, Francuska Str. 20/24, 40-027

Katowice, Poland, tel: +48 602720948; fax: +48 322561182;

E-mail: annadlis@neostrada.pl

Running title: Neurological abnormalities in localized scleroderma

Key words: scleroderma en coup de sabre; progressive facial haemiatrophy; neurological

pathology

1
Abstract

Introduction: Localized scleroderma (LoS) of the face and head is often associated with

neurologic manifestations and/or imaging abnormalities in the central nervous system (CNS).

Case series: We present an analysis of 20 cases of LoS affecting the face and head. The CNS

symptoms and/or abnormalities in high-resolution computed tomography (HRCT) and/or

magnetic resonance imaging (MRI) were observed in 12 patients (60%). In addition to the

mild and unspecific disorders (e.g. headaches), serious neurological complications probably in

the course of vasculitis were revealed: epilepsy (in 2 patients), epilepsy and pyramidal sings

(in 1 patient). Neurological disorders and LoS occurred at the same time (in 3 patients) or at

the course of the disease (9 patients) and no later than 29 years since the onset of the disease.

No link between neurological disorders and the LoS clinical morphology, immunological and

other laboratory parameters has been established.

Conclusions: CNS involvement is not correlated with the clinical course of the facial and head

LoS and may occur years after the disease initial symptomatology. Imaging follow up is not

required if there is not any emerging neurological symptom. In some cases, however, both

HRCT and MRI are useful for monitoring disease evolution and addressing therapeutic

choices.

Introduction

Localized scleroderma (LoS), also known as scleroderma circumscripta or morphea, is a

rare, inflammatory skin disorder that affects the dermis and sometimes subcutaneous tissues

(fascia, muscle, and underlying bone), with incidence 2.7 per 100.000 people.1 The etiology

and pathogenesis are not completely understood: autoimmunity, environmental factors,

infection, and trauma may trigger cytokine production and release that are responsible for
2
increased fibroblast and collagen synthesis. LoS rarely affects the face and/or head which is

the case in scleroderma en coup de sabre (SCS) and/ or progressive facial haemiatrophy

(PFH). Both disease subtypes occur predominantly in children. According to a large

international study of childhood-onset LoS 23% of children had a facehead localization

(linear head), including 13% for SCS and 10% for PFH.2 Adult-onset SCS constituted only

2,4 - 4,4% and PFH 0,3-1% of LoS in adult cohorts. 3-5 The disease is confined to the affected

areas and there is no evidence of internal organs involvement. However, in Zulian et al. study

neurologic or ocular findings were observed in 40% of children with LoS of the head.2 Some

recent reviews explored the neurologic manifestations in such patients. with LoS of the face

and head. Kister et al.1 reviewed 54 case descriptions of craniofacial LoS with neurological

symptoms and neuroimaging findings. Seizures (42-73%) and headaches (19-29%) were the

most frequent neurological disturbances.6,7 Amaral et al.2 identified 50 case reports/studies

referring to neurological involvement in SCS and 224 LoS patients in total. Epilepsy was the

most frequently reported neurological alteration, present in 37 SCS patients with a total of 42

events (42%).2 A total of 19 patients were identified with headache (19%).2 Cranial nerve

involvement occurred with a total of 8 events in 10% of patients.7 Pyramidal signs (including

hemiparesis) were observed in 7 patients 8% of patients.7 Some authors reported also a high

prevalence of ophthalmological changes in their patients especially in the SCS subtype of

juvenile LoS.8,9 Ocular disorders were frequent in PFH and included corneal and retinal

changes, and the most common neuro-ophthalmological disorders involved ocular and

pupillary dysfunction. 10 According to Tollefson and Witman11 cranial high-resolution

computed tomography (HRCT) and/or magnetic resonance imaging (MRI) findings in

patients with SCS/PFH and neurological disease were usually ipsilateral, supporting the

theory that these neurological manifestations may be directly linked to the cutaneous disease.

3
Some authors suggested that neuroimaging may be useful for monitoring disease activity in

SCS.12

Therefore, the aim of this study was to establish the correlation between neurological

changes and specific clinical features and laboratory data in patients with LoS of the face and

head.

Methods

The study included 20 patients (19 women and 1 man- No 9) with LoS of the face and

head. The age of subjects ranged from 18 to 62 years and the mean age was 38.314.9 years.

LoS was classified according to the European Society of Pediatric Rheumatology criteria.13

The age at disease onset ranged from 10 to 59 years and the average age was 24,815,3. In 6

patients the first symptoms appeared before the age 16. All the patients were subjected to a

detailed medical history and physical examination (including neurological and

ophthalmologic examination). The disease activity was determined based on the clinical

parameters presence of the erythematous to violaceous, edematous, or sclerotic lesions

with a characteristic violaceous ring and/or progression involving deeper tissue (subcutaneous

tissue, fascia, muscles and bones). Additionally, the following laboratory tests were

performed: ESR, CRP, FBC, peripheral blood smear, protein electrophoresis, rheumatoid

factor, and the following was determined: antinuclear antibodies (ANA) by means of indirect

immunofluorescence on HEp-2 cells, IgG and IgM antibodies against Borrelia burgdorferi by

ELISA, muscle enzymes and liver and kidney functions tests. After the neurological

consultations, all the patients had the CNS imaging performed: HRCT and/or MRI. They

were also ordered to run CNS imaging follow-up and they were scanned again after 3 years.

Ethical approval: the approval of ethics committee of Medical University of Silesia (ref.

1278/2008).

Results

4
Some clinical data, laboratory and neuroimaging findings are presented in table 1 and 2.

Eighteen patients were diagnosed with SCS, 1 patient (No 10) with linear LoS in the chin

area, 1 patient (No 11) with plaque LoS of the left cheek and upper lip. In 7 patients (6

diagnosed with SCS and one with linear LoS of the chin), PFH occurred (No 1-4, No 10, 13,

14). In 6 patients (No 1, 2, 11, 13, 16, 19), skin lesions were located on the left side, in 10

cases on the right side and 3 patients (No 6, 5, 20) experienced changes in the central part of

the face. In 13 patients with SCS, skin lesions affected only the forehead, in 4 patients (No 3,

4, 10, 12) the forehead and scalp (parietal area) and in one patient (No 6) the forehead

and chin. In cases No 3, 4, 10 and 12, SCS was accompanied with plaque LoS on the trunk

and in patient No 10 additionally on the legs. The duration of the disease estimated based on

the occurrence of the first dermatological symptoms related to LoS of the face and/or head

was 1 to 40 years, 14.710.4 years on average. Nine female patients (No 1, 3, 5, 8, 11, 13, 15,

19, 20) reported progression of skin lesions. The average time from the onset of symptoms to

examination of these patients was 14,414,1 years, ranged from 1 to 30 years. Only 4 patients

were recently diagnosed (the disease duration less than 5 years).

The CNS symptoms and/or radiological findings were observed in 12 patients. A migraine

was reported by 6 patients, in 3 cases epilepsy was observed, 2 patients complained of

paraesthesia of half of the face, 1 patient had facial paralysis on the side affected with SCS. In

patient No 3 SCS and PFH lesions were located on the right side, whereas the neurological

examination showed subtle pyramidal signs in the left limbs. The following were also

observed in this patient: slight generalised muscle weakness in four limbs and sensory

neuropathy characteristics of demyelination type in the lower limbs. In 3 patients

dermatological and neurological manifestations appeared at the same time, in 9 patients

neurological changes occurred or were revealed by the CNS imaging after a period of 1 to 29

years, 8.5+10.3 on average. At the age of 14, the patient No 3 started suffering from SCS and

5
PFH with coexistent migraines, then when the subject was 26, epilepsy occurred together with

abnormalities in neurological examination (pyramidal signs, see above) and the head MRI and

angiography revealed vasculitis. During these investigations, a lumbar puncture was

performed, and cerebrospinal fluid analysis was unremarkable.

By means of HRCT and MRI various abnormalities were detected in 4 patients with SCS

(No 1-4) and in 4 patients with comorbid PFH (No 5-8). In 8 patients, including 2 with co-

morbid PFH (No 13, 14), there were no neurological manifestations in the medical history,

physical examination and the CNS imaging. Nonetheless, patient No 13 experienced dizziness

and tinnitus on the side affected by SCS and in patient No 20 syncope occurred. Ten patients

showed positive ANA: in 6 patients in a speckled pattern, another 3 in a homogenous and

speckled pattern and in one in a nuclear pattern. Seven patients with positive ANA displayed

neurological symptoms and/or abnormalities in the brain scans. However, such disorders were

also observed in 5 cases where patients had negative ANA. In any case a follow-up HRCT

and MRI scans did not detect significant differences compared to the initial examination.

In 3 patients ophthalmologic abnormalities were observed. In two patients (No 2, 16) the

changes related to retinal angiopathy (vascular tortuosity). In the case No 2, epilepsy was

diagnosed accompanied by changes in MRI scans as described above. In the patient No 16,

no neurological manifestations were observed. In the case No 5, optic nerve disc drusen,

headaches and the calcifications of the cerebral falx were revealed.

Due to neurological disorders, symptomatic treatment was initiated (including anti-

epileptics, etc.). In one case (No 3), due to documented process of brain vasculitis,

corticosteroid therapy and immunosuppressive drugs (pulse therapy with cyclophosphamide

and methylprednisolone) were administered with good results.

Discussion

6
 Over past 10 years there have been a number of reports concerning the occurrence of

neurological and ophtalmological abnormalities associated with SCS/PFH.6-12,14-17 The crucial

problem to be solved is determining if the neurologic findings in these patients (either clinical

or radiographic) are related to their LoS or whether these are coincidental. We presented an

analysis of 20 cases of LoS affecting the face and head with a frequent CNS involvement in

the SCS and PFH cases, regardless of the time of presentation of cutaneous indurations, with

or without coexistent plaques of LoS in other locations. Similarly to findings of Kister et al.6

and Blaszczyk et al.14, in the most cases dermatologic symptoms preceded CNS involvement.

Although, in 16% of cases described by Kister et al.6 neurological symptoms predated the

cutaneous manifestations, we observed such manifestation in none of our cases. According to

Holland et al.15, long and careful follow-up of SCS patients provide evidence that

neurological abnormalities may develop at any time during the course of the disease. We

confirmed these observations, LoS of the face and head in our patients had very long periods

of quiescence followed by reactivation, without correlation between disease duration. In

addition to the mild and unspecific disorders (e.g. headaches), serious neurological

complications in the course of vasculitis were revealed in our case series. The results of the

immunosuppressive treatment were successful. Beneficial effects of such therapy on

neurological lesions in patients with PFH were observed also by other authors.12,16 Our study

confirmed also that the changes in the brain scans (calcifications, impaired cerebrospinal

fluid, extracerebral tumor) may be detected in patients with SCS/PFH who did not report or

experience any abnormalities in neurological examination. Similarly to Careta et al.,8 in all

the patients, imaging findings after 3 years were unchanged. Our observations seem to be also

consistent with those of a recently published by Doolittle et al.17 According to these authors,

imaging findings often do not progress, regardless of cutaneous disease activity and are

inconsistently associated with clinical abnormalities. Additionally, no link between

7
neurological disorders and the presence of positive ANA and other studied laboratory

parameters has been established in our cases. This tends to provide further evidence that the

detection of ANA in the context of LoS is merely an epiphenomenon of unclear pathogenetic

relevance. While Littman et al. 18 and Miyamoto et al.19 reported spinal cord lesions as rare

and difficult-to-find (possibly underestimated) neurological manifestation that can be

associated with LoS, the authors of the present study did not observe such involvement.

Ocular abnormalities were also not frequently associated with the CNS involvement and were

not specific.

Conclusions

CNS involvement is not correlated with the LoS clinical morphology and its activity and

may occur years after the disease initial symptomatology. Imaging follow up is not required if

there is not any emerging neurological symptom. In some cases, however, both MRI and

HRCT are useful for monitoring disease evolution and addressing therapeutic choices.

Conflict of interest: all authors declare they have no conflicts of interest

References

1. Peterson LS, Nelson AM, Su WP, Mason T, O'Fallon WM, Gabriel SE. The

epidemiology of morphea (localized scleroderma) in Olmsted County 1960-1993. J

Rheumatol. 1997;24:73-80.

2. Zulian F, Athreya BH, Laxer R, Nelson AM, Oliveira SKF de, Punaro MG, et al.

Juvenile localized scleroderma: clinical and epidemiological features in 750

children. An international study. Rheumatology (Oxford) 2006;45:614620.

3. Mertens JS, Seyger MMB, Kievit W, Hoppenreijs EPAH, Jansen TLTA, van de

Kerkhof PCM, et al. Disease recurrence in localized scleroderma: a retrospective

analysis of 344 patients with paediatric- or adult-onset disease. Br J Dermatol

2015;172:722728.

8
4. Kreuter A, Wischnewski J, Terras S, Altmeyer P, Stcker M, Gambichler T, et al.

Coexistence of lichen sclerosus and morphea: A retrospective analysis of 472

patients with localized scleroderma from a German tertiary referral center. J Am

Acad Dermatol 2012;67:11571162.

5. Marzano AV, Menni S, Parodi A, Borghi A, Fuligni A, Fabbri P, et al. Localized

scleroderma in adults and children. Clinical and laboratory investigations on 239

cases. Eur J Dermatol 2003;13:171176.

6. Kister I, Inglese M, Laxer RM, Herbert J. Neurological manifestations of localized

scleroderma: a case report and literature review. Neurology 2008,71 pp.1538

1545.

7. Amaral TN, Peres FA, Lapa AT, Marques-Neto JF, Appenzeller S. Neurological

involvement in scleroderma: A systematic review. Semin Arthritis Rheum

2013,43:335-347.

8. Careta MF, Leite Cda C, Cresta F, Albino J, Tsunami M, Romiti R. Prospective study

to evaluate the clinical and radiological outcome of patients with scleroderma of

the face. Autoimmun Rev 2013,12:1064-1069.

9. Zannin ME, Martini G, Athreya BH, Russo R, Higgins G, Vittadello F, et al. Juvenile

Scleroderma Working Group of the Pediatric Rheumatology European Society

(PRES).Ocular involvement in children with localised scleroderma: a multi-centre

study. Br J Ophthalmol 2007,91:1311-1314.

10. Bucher F, Fricke J, Neugebauer A, Cursiefen C, Heindl LM. Ophthalmological

Manifestations of Parry-Romberg Syndrome. Surv Ophthalmol. 2016 Apr 1. pii:

S0039-6257(15)30073-4. doi: 10.1016/j.survophthal.2016.03.009. [Epub ahead of

print]

9
11. Tollefson MM, Witman PM. En coup de sabre morphea and Parry-Romberg

syndrome: a retrospective review of 54 patients. J Am Acad Dermatol

2007,56:257-263.

12. Chini L, Orlacchio A, Silenzi R, Della Gatta F, Iannini R, Monteferrario E et al.

Neuroimaging is useful for monitoring disease activity in linear scleroderma "en

coup de sabre. Minerva Pediatr 2014,66:89-93.

13. Laxer RM, Zulian F. Localized scleroderma. Curr Opin Rheumatol. 2006,18:606-13.

14. Blaszczyk M, Krlicki L, Krasu M, Glinska O, Jablonska S. Progressive facial

hemiatrophy: central nervous system involvement and relationship with

scleroderma en coup de sabre. J Rheumatol 2003,30:1997-2004.

15. Holland KE, Steffes B, Nocton JJ, Schwabe MJ, Jacobson RD, Drolet BA. Linear

scleroderma en coup de sabre with associated neurological abnormalities.

Pediatrics 2006,117:e 132-136.

16. Korkmaz C, Adapinar B, Uysal S. Beneficial effect of immunosuppressive drugs on

Parry-Romberg syndrome: a case report and review of the literature. South Med J

2005,98:940-942.

17. Doolittle DA, Lehman VT, Schwartz KM, Wong-Kisiel LC, Lehman JS, Tollefson

MM. CNS imaging findings associated with Parry-Romberg syndrome and en

coup de sabre: correlation to dermatologic and neurologic abnormalities.

Neuroradiology. 2015;57:21-34.

18. Littman BH. Linear scleroderma: a response to neurologic injury? Report and

literature review. J Rheumatol. 1989;16:11351140.

19. Miyamoto M, Kinoshita M, Tanaka K, Tanaka M. Recurrent myelitis in localized

scleroderma. Clin Neurol Neurosurg. 2014;127:140-142.

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Table 1. Characteristics of patients with neurological manifestations

No Age at LoS Neurologic Other ANA titer HRCT and MR findings

disease Diuration Signs diuration

onset (years)
(years)
(years)
1. 59 3 No signs N/a Arterial Granular 340 Expansion of the pericerebral space around the frontal
lobes, asymmetry of the anterior cerebral arteries and
hypertension slight intracranial internal carotid artery calcifications.

2. 24 21 Epilepsy 4 Retinal angiopathy Negative Hemiatrophy of the left cerebral hemisphere and right
cerebellar hemisphere, periventricular leucomalatia and
vascular tortuosity diffused postischaemic degenerative demyelinating
changes in both cerebral hemispheres.
3. 16 17 Headache, 17 None Negative A hypertensive area on the right side of caudate
nucleus, visible in T2-weighted images and improved
Epilepsy, 5 after the administration of IV contrast which is the sign
of the damage to the blood-brain barrier as a result of
Pyramidal vaculitis, focus of similar characteristics in the area of
the right lateral ventricle core.
signs

4. 10 15 No signs N/a None Homogenic Impaired cerebrospinal fluid.

granular 160

5. 51 11 Headache, 5 Optic nerve disc Granular 160 Calcification of the cerebral falx.

Depression drusen,
 Arthralgia

6. 20 11 Epilepsy 4 Homogenic Single focus in the white matter of the left hemisphere
of uncharacteristic image, most likely a vascular lesion.
granular 160

7. 30 9 No signs None Negative Extracerebral tumor within the recessus pinealis

(teratoma?).
8. 17 40 Headache 20 Arterial Negative The areas of decreased density within the white matter
of cerebral hemispheres indicating the presence of
hypertension chronic vascular changes of moderate intensity.

Borreliosis

Arthralgia

9. 12 19 Facial 4 None Negative No abnormalities detected

paralysis,

Paraesthesia

10. 14 10 Paraesthesia 1 Head trauma Negative No abnormalities detected

11. 27 1 Headache, 1 None Negative No abnormalities detected

Paraesthesia

12. 11 23 Headache 10 Borreliosis Granular 160 No abnormalities detected

Table 2. Characteristics of patients without neurological manifestations

No Age at LoS Other ANA titer

disease
onset Diuration
(years)
(years)

13. 55 4 Dizziness and tinnitus Granular 640

14. 37 8 Arthralgia, asthma Homogenic, granular 320

15. 22 23 Raynaud, arthralgia Granular 640

16. 10 8 Retinal angiopathy (vascular Negative

tortuosity), borreliosis

17. 10 14 Borreliosis Negative

18. 15 30 None Negative

19. 30 30 Raynaud Negative

20. 20 1 Raynaud, syncope Granular 640