Journal of Neurology, Neurosurgery, and Psychiatry 1983;46:261-265

Progressive leptomeningeal fibrosis: a
clinico-pathological case report
DAVID CHALIF, LEO W DUCHEN, JOHN MARSHALL, RICHARD HAYWARD
From the Departments of Clinical Neurology, Neuropathology, and Neurosurgery, Institute ofNeurology,
The National Hospital for Nervous Diseases, Queen Square, London, UK
SUMMARY A female patient developed persistent facial pain beginning at age 19 years. Intermittent motor and sensory disturbances referable to one hemisphere began nine years later and by

the age of 41 she had developed signs of increased intracranial pressure. Exploratory craniotomy
revealed replacement of the leptomeninges by thick, fibrous tissue. The histological appearance
was that of a chronic, benign and minimally infiltrative process with a mild, non-specific
inflammatory component, underlying cortical ischaemic changes, and white matter oedema. The
lesion resembled nodular fasciitis, a soft tissue process. No cause of the reactive fibrosis of the
meninges in this case is known.
Benign fibrous lesions occur commonly in the soft
tissues yet rarely in the CNS or meninges. The
reported cases of intracranial fibroblastic proliferative processes form a spectrum histopathologically,
and usually present as well defined discrete
tumours.' Leptomeningeal fibrosis may follow cranial irradiation2 and sub-arachnoid haemorrhage3
but does not appear to have been reported as an
idiopathic entity. We report a case of diffuse fibrosis
of the leptomeninges of the right hemisphere in an
otherwise healthy 41-year-old female who was
aware of progressive symptoms referable to that
hemisphere for more than 20 years.
Case report

The patient is a 41-year-old right handed female surveyor,
who first came to attention at the National Hospital,
Queen Square in 1972. She had suffered from persistent
right facial pain in the first two divisions of the fifth cranial
nerve for over 20 years, at times associated with rightsided headache. For four years she had experienced
episodes of numbness lasting several days, over the left
side of the body associated with vague clumsiness of the
left hand. There was one isolated episode of loss of con-

sciousness associated with a numb sensation in the left leg.
Neurologic examination and general physical examination
were negative. EEG and EMG were normal. A radioDr D Chalifs present address, and address for reprint requests:
Department of Neurosurgery, New York University-Bellevue
Medical Center, 550 First Avenue, New York, NY 10016, USA.

Received 28 September
Accepted 29 October 1982

isotope brain scan showed an area of increased uptake in
the right parietal region, however four-vessel angiography
was normal. The patient was discharged with a presumptive diagnosis of migraine.
She presented next in 1976 with clumsiness of the left
arm starting acutely several weeks prior to admission and
slowly subsiding. In the interim period (1972-76), the
left-sided motor-sensory phenomena had subsided, but the
right facial pain had persisted. Neurologic examination
showed left-sided hyperreflexia and mild weakness. There
was no papilloedema. Lumbar puncture yielded clear colourless fluid with an opening pressure of 140 mm water, no
cells and a normal biochemical profile. There was no
oligoclonal pattern. CIT scan (fig la) showed a low density
area in the right parietal lobe which enhanced with contrast. No mass effect was appreciated. EEG demonstrated
a right anterior quadrantic disturbance; regional cerebral
blood flows were normal. Right carotid angiography
showed small abnormal tortuous vessels over the right
posterior frontal convexity, supplied mainly by a dilated
anterior middle meningeal artery. The angiographic picture was thought to be consistent with low grade glioma.
As the patient had minimal neurologic deficit and as the
lesion was ill-defined, surgical exploration was deferred,
and she was discharged to be followed as an out-patient.
The patient was re-admitted in 1981 for investigation.
The right-sided facial pain had remained constant although
the right-sided headache had increased in severity and
would at times wake her at night. About two weeks prior to
admission she had developed a slowly progressive leftsided numbness and she continued to have intermittent
episodes of left-sided motor and sensory disturbances.
There were no other symptoms. Family and past medical
history were non-contributory. Over the previous 20 years
the patient had taken a number of drugs for relief of
headaches and facial pain, including aspirin, codeine phos-

261

262Chalif, Duchen, Marshall, Hayward
262

Fig 1 The non-contrast computed tomographic scan in 1976 (A) demonstrates a small low
density area in the right fronto-parietal region. By 1981 (B) this low density area has spread to the
entirety of the right frontal and parietal lobes. The low density is confined to the white matter and
extends down to the internal capsule. There are small areas of calcification visible anteriorly and
there are further high density areas in or adjacent to-the parietal cortex. After intravenous contrast
infusion (C) selective cortical enhancement is noted, along with a slight right to left shift.

phate, paracetamol, propoxyphene and benzodiazepines.
Specifically, there was no history of methysergide ingestion.
Examination revealed an alert, intelligent woman with
mild pyramidal weakness and hyper-reflexia on the left
side. Plantar responses were flexor. There was mild blurring of the optic discs and fluorescein retinal angiography
showed early papilloedema. Repeat CT scan (figs lb, c)
demonstrated extensive areas of low density in the right
hemisphere, with marked cortical enhancement after contrast infusion. Bilateral carotid angiography disclosed diffuse swelling of the right cerebral hemisphere. The areas of
abnormal circulation in the right posterior frontal region
were persistent and the contribution of the meningeal circulation was more apparent than previously.
The patient was started on steroids with some clinical
improvement and underwent right frontal craniotomy for
biopsy and decompression. The surface of the brain was
grossly abnormal and were covered in most areas with a
3-4 mm thick layer of firm, pinkish tissue which was lightly
adherent to the overlying dura. Dilated meningeal arteries
were seen in the dura adjacent to the thickened leptomeninges. In some areas where the brain was not
covered by the abnormal tissue the arachnoid had a white
discoloration and was thickened along some, of the sulci.
Following operation the patient made an excellent
recovery. Treatment with steroids continued for several
weeks during which time there was a continuing improvement in her left sided weakness. She was then able to exist
without steroid therapy for several months but approximately one year after her operation she was re-admitted
with a short history of deterioration during which her
hemiplegia had worsened. At the time of her arrival at
hospital some spontaneous improvement had started.
Treatment with steroids was started once again and continued for several weeks. Further CT scans performed during this recurrence of her symptoms at first showed
increased oedema in the right hemisphere but later scans

demonstrated resolution of this oedema. At the time of
writing she is back at work with only a slight increase in her
hemiplegia compared with that noted prior to her operation.
Pathology

The operative specimen received consisted of brain tissue
15-2-0 cm in thickness including the frontal pole and adjacent gyri with underlying white matter. Many blocks were
prepared so that the whole specimen has been embedded
in paraffin wax. A wide variety of staining methods were
used. The description which follows applies to every block
studied with only minor variations. There was generalised
thickening of the leptomeninges varying from about 100
gm in thickness over some gyral convexities (fig 2) up to
15-2-0 mm in the sulci. In places the leptomeninges were
cellular, composed of plump fibroblast-type cells (fig 3)
lying in a loose reticulin-rich matrix and showing moderate
numbers of mitotic figures. There were scattered clusters of
lymphocytes, some around vessels, but no necrosis,
granulomas or plasma cells. No organisms were identified
with appropriate staining techniques for bacteria or fungi.
In other places the meninges were densely collagenous
with few cells, and here and there small vessels and collagen had an eosinophilic hyaline appearance (not positive
for amyloid). Arterial and venous vessels were present
within the thickened leptomeninges as well as
endothelium-lined channels. Although vessels were
numerous in some places, particularly in sulci, the tissue
was not vascular enough to be considered angiomatous and
only occasional granules of haemosiderin pigment were
present, too little to indicate previous bleeding. Vessels
were surrounded by concentric layers of collagen and some
seemed to be constricted by the dense surrounding tissue.
Several vessels were seen which have a greatly narrowed
lumen because of intimal thickening and smooth muscle
proliferation suggesting previous occlusion and recanalisa-

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Fig 2 Section showing meninges and underlying cerebral
cortex at the convexity of a gyrus. There is marked
thickening ofthepia-arachnoid (arrow) which is here about
200 pn thick, densely collagenous with a scattering of
lymphocytes. There are no granulomas. Immediately below
thepia there is a broad (about 80,pm) band ofglialfibres (*)
and the molecular layer beneath shows reactive astrocytic
gliosis. (Haematoxylin and eosin x 40.)

tion. There was no arteritis or phlebitis and no acute
thrombosis. Perivascular fibrosis was seen around some
vessels in the white matter (fig 4) and may represent an
extension of the fibrous lesion along Virchow-Robin
spaces.

The underlying brain showed changes which could
almost certainly all be interpreted as secondary to the
meningeal and vascular pathology. A layer of dense
astrocytic glial fibres, strongly stained by the Holzer
method, lay immediately beneath the pia and occupies the
superficial 100-200 ,tm of the molecular layer. The
remainder of the molecular layer showed an increased
number of astrocytes and in places these were of the reactive type with abundant eosinophilic cytoplasm. Several
areas of cortex showed ischaemic changes, the most severe
being around the depths of some sulci with laminar necrosis, capillary and glial proliferation and abundant fat
granule cells. One of these areas of cortical necrosis was
much older than the others and shows abundant collagen
formation within the softened zone. White matter beneath
the necrotic areas of cortex showed astrocytic gliosis, some
myelin loss and, in places, oedema.

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Fig 3 Section showing a cellular area of meninges.
Fibroblasts and occasional lymphocytes lie in a loose matrix
which, with appropriate staining, can be shown to be rich in
reticulin fibres but contains little collagen. (Haematoxylin
and eosin x 100.)

Discussion
Benign lesions composed of fibrous elements, commonly termed fibrous dysplasias, desmoids,
fibromas, and fibromatoses are exceedingly rare in
the CNS and meninges. A review of the differential
diagnosis of fibrous intracranial lesions' indicates
that the lesion we report is histologically unique.
Benign fibrous proliferations make up a variety of
soft tissue masses and are generally classified into a
group of lesions known as the fibromatoses. The
fibromatoses form a spectrum of processes and are
best defined as locally invasive, idiopathic, nonmetastasising fibrous tumours which are of mesenchymal origin and recurrent after surgical excision.4-6 Among the fibromatoses are entities such as
palmar fibromatosis, Dupuytren type fibromatosis,
and congenital generalised fibromatosis. Histologically these lesions are viewed as neoplastic tissue
which continues to proliferate, thereby becoming an

264

Fig 4 Section through gliotic white matter. A small blood
vessel, probably venous, is shown surrounded by a thick
peri-vascular layer of dense collagen. (Haematoxylin and
van Gieson x 100.)

infiltrating local mass. Proliferation of fibroblastic
elements can also be classified as reactive or
inflammatory phenomena,5 as in the case of postirradiation fibrosis,27 post subarachnoid haemorrhage fibrosis3 and nodular fasciitis.8 The histopathologic and aetiologic variability of benign
fibrous lesions make strict classification difficult. It
appears however, that the leptomeningeal fibrosis
we report has properties of both the fibromatoses
and the reactive fibrous lesions.
To date there are less than 20 reports in the literature of benign CNS and meningeal fibromas or
fibromatoses, and these form a variety of lesions
ranging from the so-called fibroblastic meningioma
to post-irradiation intracranial fibromas.' 29-19 Histologically these tumours were somewhat variable;
however, each showed dense growth of fibrous tissue and stained densely for collagen and reticulin.
Few mitoses were noted and there were no reports
of metastases. It is of note that except for one isolated report of dural fibrosis presenting as infantile
spasms,'4 all other CNS fibrous lesions were dis-

Chalif, Duchen, Marshall, Hayward
crete, well circumscribed intracranial tumours, often
accompanied by a significant mass effect. In addition
to hemispheric masses, an intra-cerebellar lesion'7
and an intramedullary thoracic lesion' have been
observed. Fibrous tumours of bone, ossifying
fibromas, are also known to occur intracranially,
arising from the craniofacial bones.2022 In contrast,
the fibrous process in the present case is not tumorous in character and is confined to the leptomeninges and adjacent vessels. Macroscopically,
the leptomeninges were thickened at surgery and
histopathologically the lesion shows a diffuse proliferation of fibroblastic elements in the
leptomeningeal plane.
Radiographically, pan-hemispheric low density
was noted and the unusual feature of selective cortical enhancement extending from frontal to occipital
lobes suggests that the process spread diffusely
through the leptomeninges over the right hemisphere. The low density, which had been progressive
since the previous scan, may reflect oedema and
reaction to widespread zones of laminar cortical
infarction which were found histologically. These
zones of infarction are thought to be a result of
perivascular fibrosis and the occlusion of vessels in
the sub-arachnoid space and cortex. Arteritis was
not noted histologically, but dilatation of the
meningeal vessels was seen both on angiography and
at surgery.
The lesion appeared to be chronic histologically
and survey of the specimen showed varying degrees
of density and organisation of the fibrous cellular
elements. The symptom of right sided facial pain
may indicate that this lesion was clinically long
standing, as the pain could represent chronic trigeminal irritation or the effect of the documented
engorgement of right hemispheric meningeal vessels.
The fibrotic leptomeninges are strikingly similar
histologically to the soft tissue mass termed nodular
fasciitis. This is a fascial mass composed of lobules of
fibroblasts, capillaries, a scant chronic inflammatory
cell infiltrate and areas representing granulation tissue in a myxoid stroma or collagen matrix.823 Nodular fasciitis has been called a "reactive" phenomenon in the soft tissues.8 In the case reported,
although there was sub-pial gliosis, there was no
clear source of meningeal irritation. Additionally,
although this leptomeningeal lesion is histologically
similar to nodular fasciitis, the clinical characteristics
differ and here the lesion appeared to be somewhat
more locally infiltrative. Although there is no evidence of direct extension into the cortex, perivascular fibrosis was noted in both grey and white matter
subjacent to the thickened leptomeninges. This
fibrosis seems to occupy the perivascular Virchow-

Progressive leptomeningeal fibrosis: a clinico-pathological case report

265

Robin spaces. The presentation differs also, as the 6 Stout AP. Tumours of the soft tissues. In: Atlas of
Tumour Pathology, Section 2, fascicle 5: Armed
patient reported here had a slowly progressive 24
Forces Institute of Pathology, Washington DC, 1967.
year history, while the reactive fibroses commonly
'Petit UD, Chamness JT, Ackerman LV. Fibromatosis
have a much shorter clinical course.
and fibrosarcoma following irradiation therapy.
Radiation therapy7 and chemotherapeutic
Cancer
1954;7:149-58.
agents24 have been implicated as aetiological factors
Price EB, Silliphant WM, Schuman R. Nodular fasciitis:
causing aberrent growth of fibrous tissue. Quest et
A clinico-pathologic analysis of 15 cases. Am J Clin
at2 report excision of a frontal fibrous tumour followPathol 1961;35:122-36.
ing cranial radiation therapy and CNS fibrosarcoma 9Alpers BJ, Grant FC, Yaskin J. Primary fibroblastoma of
is well documented following irradiation.25
the brain. Arch Neurol Psychiat 1931;26:1335 (abstract).
Methysergide, an ergotamine derivative used as an
antimigraine agent, has been implicated as a cause 10Amezua L. Fibroma intracerebral gigante recidivado
Hibemacion artificial. Acta Neuropsiquiat Argent
of retro-peritoneal fibrosis.24 There is, however, no
1958;4: 15-22.
evidence in the literature of drug induced intracra- " Baker
AB, Adams JM. Primary fibroblastoma of the
nial fibrosis in man. Subarachnoid haemorrhage is
brain.
of a case. Am J Pathol 1937;13: 129-37.
well known to cause fibrosis of the leptomeninges,3 12 Brucher Report
JM, Hizawa K, Wechsler W. Ultrastructure
usually basal, often leading to communicating hyd'un fibrome intracerebral et possibilite de transfordrocephalus. In this case there was no history or
mation maligne de ce type tumoral. Rev Neurol
clinical evidence of subarachnoid haemorrhage,
(Paris) 1970;123:443-5.
irradiation, trauma, infection or the use of 13 Carrillo R, Ricoy JR, Herrero-Vallejo J, et al. Fibrous
xanthomas of the brain. Report of two cases. Clin
methysergide.
Neurol Neurosurg 1975;78:34-40.
It is difficult to categorise formally this idiopathic
CL, Crichton JU, Jones EA, et al. Fibromatosis
leptomeningeal fibrosis. Developmentally, it is pre- 14 Dolman
of the dura presenting as infantile spasms. J Neurol Sci
sumed that fibrous tumours of the CNS arise from
1981;49:31-9.
mesenchymal precursors in the leptomeninges and .s Kepes
JJ, Kepes M, Slowick F. Fibrous xanthomas and
dura or from perivascular connective tissue, and
xanthosarcomas of the meninges and brain. Acta
have therefore been called "congenital neoplasms"
Neuropathol 1973;23: 187-99.
by Koos et al,'6 rather than true neoplasms. A 16 Koos WJ, Jellmeyer K, Sunder-Plassmann M.
Intracerebral fibroma in an 11 month old infant. Case
fibroma involving the dura has been described in a
report. J Neurosurg 1971;35:77-81.
five month old child with congenital generalised
fibromatosis.26 Conditions such as tuberous sclerosis '7Llena JF, Chung HD, Hirano A, et al. Intracerebellar
"fibroma". Case report. J Neurosurg 1975;43:98and neurofibromatosis, which are associated with a
101.
proliferation of fibrous elements within the CNS, 18 Scott
M, Peale AR, Croissant PD. Intracranial midline
must be considered when interpreting the pathology
anterior fossae ossifying fibroma invading orbits,
in this case although the patient had none of the
paranasal sinuses, and right maxillary antrum. Case
stigmata of these disorders.
report. J Neurosurg 1971;34:827-31.
We thank Professor du Boulay for the neuroradiological reports and for figure 1.
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