Neuroimaging CPC

A 67-Vear-Oid Woman with
Polymyalgia Rheumatica and
Left Hemispatial Neglect

J. Paul Mahfood, MD
Division of Rheumatology
Department of Internal
Medicine
University of South Florida
Tampa, FL
Michael Gold, MD
Department of Neurology
University of South Florida

America Gonzalvo, MD
Department of Pathology
University of South Florida
Joanne Valeriano-Marcet,
MD
Division of Rheumatology
Department of Internal
Medicine
University of South Florida

--------------------------------------------------------

ABSTRACT
A 67-year-old woman with a diagnosis of polymyalgia rheumatica presented initially wih periods of confusion and incontinence_ ACT scan of the brain was normal and she was treated
with tapering doses of corticosteroids and clinical improvement
After a brief period off steroids, the patient presented with a
progressive dementia, left-sided clumsiness, gait disturbances
and left hemispatial neglect An MRI at this time demonstrated
a large area of edema over the right parietal lobe and intense
cortical enhancement A chest CT demonstrated multiple nodules_ Biopsies of the lung and brain failed to identify any infectious organisms or malignant tissue_ The leptomeningeal biopsy
revealed multiple granulomatous areas with central necrosis and
hystiocytic cells consistent with idiopathic hypertrophic pachymeningitis_
Key words: polymyalgia rheumatica, neglect, chronic meningitis,
MRI.
Mahfood JP, Gold M, Gonzalvo A, Valeriano-Marcet r A 67year-old woman with polymyalgia rheumatica and left
hemispatial neglect
J Neuroimaging 1998;8:222-227
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A 67-year-old woman was diagnosed with polymyalgia
rheumatica (PMR) and temporal arteritis (TA) at age 62
based on fatigue, polymyalgia, proximal muscle stiffness,
unilateral temporal headache, and elevated erythrocyte

Received Feb 5, 1997, and in revised form Mar 27, 1998. Accepted for publication Mar 29, 1998.
Address correspondence to Dr Gold, University of South
Florida College of Medicine, Department of Neurology MDC
55, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612.
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222

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sedimentation rate (ESR). Bilateral temporal artery biopsies and head computed tomography (CT) were both
negative. High-dose corticosteroids were associated with
clinical improvement, and the patient was continued on
chronic corticosteroid therapy with variable dose adjustments in response to symptomatic flare-ups. She did not
receive disease-modifying antirheumatic drugs and had no
prior history of connective tissue diseases. Concurrent
medical problems included type II noninsulin-dependent
diabetes diagnosed in 1991, hypertension, and osteoporotic vertebral fractures. Past surgeries included total hysterectomy at age 48 and thyroidectomy at age 54.
In May 1995 she experienced episodes of confusion and
bladder incontinence for which a brain CT, with and without contrast, was reported to be normal. She was tapered
off corticosteroids in August 1995 following stable clinical
improvement and stabilization. Magnetic resonance imaging (MRI) with contrast, performed 1 month later, was
compared with the previous CT and revealed no mass
lesions or abnormal enhancement. An ophthalmologist reported no evidence of retinal degeneration, optic neuropathy, or any symptoms ofT A. While temporarily off corticosteroids she presented to a neurologist with symptons
of mild, unexplained weight loss, gait imbalance, left-side
weakness, clumsiness of her hands, variable cognitive deficits, myalgia, and fatigue. Examination revealed an amnestic disorder, anomia, ideomotor praxis, preservative
behaviors, and left hemispatial neglect on line bisection
and target cancellation tasks. The cranial nerves were normal except for extinction to double simultaneous visual
stimulation. The tone of the left arm was increased and a
subtle weakness was difficult to dissociate from motor intentional neglect. No extrapyramidal features were noted.
Fine touch and pinprick were diminished on the right upper arm without a radicular pattern. There was extinction
to double simultaneous extinction to left-side stimuli.

Copyright© 1998 by the American Society of Neuroimaging

Deep tendon reflexes were brisker on the left upper and
lower extremities.
Corticosteroid therapy was resumed prior to referral to
a rheumatologist, who reported a normal medical examination. Outpatient laboratory evaluations revealed Wintrobe ESR, 47 mm per hour; hemoglobin, 14.4 g per deciliter; white blood cell count, 21,000 per cubic millimeter;
platelet count, 292,000 per cubic millimeter; normal thyroid function tests; and absent rheumatoid factor and antinuclear antibodies. The patient was admitted to the hospital, where another MRI was performed, and she
underwent a comprehensive evaluation. Laboratory tests,
including a hemogram, serum electrolytes, antibody serologies, and an angiotensin converting enzyme level,
were all normal, with the exception of a slightly elevated
ESR (38 mm per hour). She was placed on corticosteroid
therapy with improvements in her left-side weakness and
left hemispatial neglect for several days. Because of the
multiple nodules noted on chest CT, which were suspicious for a malignancy, a lung biopsy was performed and
was followed by an open brain biopsy. No lumbar puncture was attempted because of the mass effect noted on
MRI. She remained clinically stable on a tapering dose of
steroids until her death several months later following a
complicating episode of pancreatitis and pneumonia. The
family refused an autopsy.
Radiological Description

Brain MRI (Figs 1-3) with and without contrast material
shows extensive and patchy leptomeningeal enhancement
extending over the right temporal, right occipital, and

Fig 1. Coronal T1-weighted magnetic resonance image following intravenous gadolinium demonstrating diffuse cortical enhancement peripherally of the right parieta l lobe.

Fig 2. Axial T2-weighted mag netic resonance image w ithout
contrast demonst rating diffuse edema prima rily involvi ng the
white matter of the right parietal lobe.

right parietal lobes. Increased T2-weighted signals are
seen in the right posterior temporal and right posterior
parietal regions within the subcortical and deep white matter. The increased signal , compatible with vasogenic

Fig 3. Axial T1-weighted magnetic resonance image f ol lowing
intravenous gadolinium demonst rating diffuse cortical enhancement of the right parietal lobe w ith slight mass effect and edema.
Note the absence of ring-enhancing or focal intracranial lesions.

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223

edema, was associated with effacement and compression
of the right lateral ventricular body, posterior lateral horn,
and occipital horn. A 3-mm midline shift to the left was
noted. No abnormal enhancement was seen in the left
hemisphere. There was no evidence of tentorial herniation. An increased periventricular T2 signal was present
posterior to the left lateral ventricle and posterior horn,
suggestive of chronic microvascular changes. In addition,
diffuse cortical atrophy and extensive atrophy of both medial temporal lobes were noted.
Chest CT with and without contrast showed multiple
calcified focal nodules in both lung fields from the apex to
the base, most of which appeared to be pleural and subpleural against a background of chronic obstructive lung
disease. No hilar adenopathy was noted. Abdominal and
pelvic CT was normal. A diagnostic lung biopsy was performed initially and was then followed by an open brain
biopsy. No lumbar puncture was attempted because of the
mass effect noted on MRI.
Neurological Differential Diagnosis

This patient had a 4-year history of a rheumatological
process with corticosteroid treatment antedating the onset
of neurological problems by a period of 4 years, during
which she was treated with corticosteroids. Her initial presentation was episodic confusion and incontinence, raising
the possibility of an epilepsy or repeated near-syncopal
events. There was no report of any focal signs during or
following these episodes. She was weaned off steroids and
then developed a gradual loss of cognitive skills along with
a poorly characterized "clumsiness" of her left side. On
mental status examination, she demonstrated left hemispatial neglect on exploratory tasks (line bisection and target cancellation) and on perceptual tasks (double simultaneous stimulation), indicating a lesion of the right
parietal lobe. In addition, deficits were noted in verbal
memory, object naming, and ideomotor apraxia, indicating deficits in the left parietotemporal region. Her elemental examination suggested an upper motor neuron-type
lesion based on the clumsiness and weakness of the left
arm.
The differential diagnosis is quite broad and is complicated by her previous medical problems. The pattern of
involvement suggests a multifocal intracranial process that
became more clearly manifest after she stopped taking
steroids.
One way to approach the differential diagnosis is to
hypothesize that the patient's new signs and symptoms
were related to her recent discontinuation of steroids. A
brief, noninclusive differential diagnosis is presented in
Table 1, and revolves around neoplastic, infectious, and
inflammatory conditions. The lack of a primary tumor and
a negative biopsy of the lung nodules and the brain make
a neoplasm unlikely. Likewise, the failure to identify or
224

Journal of Neuroimaging Vol 8 No 4 October 1998

Table 1. Brief Differential Diagnosis
Diagnoses

Neoplastic

Infectious

Inflammatory
Cardiovascular disease

Symptoms

Lymphoma, carcinomatous
meningitis (small-cell carcinoma),
dural-based metastases
(melanoma), dural-based primary
tumor of the central nervous
system
Fungal (Aspergillus,
coccidioidomycosis), parasitic
(cystocercosis, amoebic),
mycobacterial, luetic/borreliosis
Vasculitis (SLE,P AN), sarcoidosis
Hypertensive lipohyalinosis,
diabetic microangiopathy

SLE = systemic lupus erythematosus: PAN = polyarteritis nodosum.

culture organisms from either lung or brain tissue makes a
chronic infection unlikely. This leaves a chronic inflammatory condition such as sarcoidosis as the most likely
cause of our patient's focal signs and symptoms.
This patient also had medical complications from
chronic steroid use (diabetes mellitus and hypertension),
which could have caused cerebrovascular disease and the
development of vascular dementia. The lack of transient
ischemic attacks or abrupt decline in cognition would argue against this option. Although there was no evidence
for systemic vasculitis, the patient could have an isolated
central nervous system (CNS) vasculitis that became active as the steroids were tapered. MRI did not reveal cerebrovascular disease in the appropriate topology to account for all the patient's signs and symptoms. Meningeal
enhancement is associated with the acute stages of cerebral ischemia but does not result in a hypertrophic meningitis, thereby making microvascular ischemic disease or
vasculitis unlikely explanations.
Alternatively one can consider processes that are unrelated to the use of steroids. A brief differential diagnosis
is presented in Table 2. Although the patient's mental
status examination and clinical presentation meet the criteria for dementia, the focal motor findings and left hemispatial neglect suggest a structural lesion, which makes a
primary degenerative process unlikely as the sole explanation.
The vasogenic edema and mass effect on MR images
suggest that the differential diagnosis can be narrowed
Table 2. Another Brief Differential Diagnosis
Mechanism

Diagnosis

Degenerative

Alzheimer's disease, frontotemporal dementia,
Pick's disease
Creutzfeldt-Jakob disease, cerebral
amyloidosis
Arteriovenous malformation
Phakomatoses

Amyloidosis
Vascular
Congenital

down to a neoplastic lesion, and an infectious or inflammatory process. Contrast enhancement did not reveal a
nidus underlying the edema, but instead revealed tremendous meningeal enhancement. Although CSF analysis
might be helpful, pleocytosis, abnormal cytology, and elevated protein levels are found with neoplasm, chronic
infection, and chronic inflammation, thereby limiting its
specificity. We believed that the most probable etiology
was a chronic infection. A brain biopsy is needed to differentiate between the remaining possibilities.
Pathological Description

The gross biopsy specimen of the left lower lung measured
5.0 x 2.5 x 2.0 em. Histological examination revealed multiple granulomatous areas with central necrosis, peripheral
palisades, and numerous clear cells with the appearance of
histiocytes (Fig 4). Gram's stain, and special fungal and
acid-fast bacilli (AFB) stains were negative. There was no
evidence of malignancy or vasculitis.
The open brain biopsy specimen measured 1.2 x 0.6 x
0.3 em. Histological examination showed cerebral cortex
with overlying arachnoidal membrane. The arachnoid
membrane revealed fibrous thickening and was infiltrated
by abundant chronic inflammatory cells, especially plasma
cells and numerous foamy histiocytes. There were noncaseating granulomatous lesions with a necrotic center
surrounded by palisading histiocytes and a few multinucleated giant cells. The arteries encased in the fibrous process showed intimal thickening without evidence of vasculitis. The underlying parenchyma showed mild reactive
astrogliosis in the superficial layers of the cerebral cortex.
The fibrotic and inflammatory process extended along the

Fig 4. Section from the left lower lobe of lung showing extensive areas of necrosis (lower left corner) and chronic granulomatous inflammation with multinucleated giant cells, without evidence of vasculitis or malignancy. No microorganisms were
identified w ith special stains (H&E, original magnification X 100
before 86% reduction).

Virchow-Robin space into the superficial cerebral cortex.
Fungal and AFB stains were negative, and there was no
evidence of malignancy (Fig 5). A pathological diagnosis
of idiopathic hypertrophic cranial pachymeningitis (IHCP)
was rendered.
Discussion

First described by Charcot and Joffroy in 1869 (cited in
Smith and Aksamit 1), IHCP is a rare disease of unknown
cause with diverse clinical, laboratory, and radiographic
manifestations suggesting a multifactorial etiology. Later
patient reports have described an intracranial process with
chronic inflammation of the dura mater leading to diffuse
thickening and fibrosis of the meninges that can interfere
with normal CNS function? IHCP may involve the cerebral parenchyma, cranium, and extracranial soft tissue. 3 It
is a diagnosis of exclusion, with a broad differential diagnosis that includes a variety of spinal 4- 7 and cranial infections4·8-12 due to multiple organisms, as well as noninfectious etiologies such as neoplasm, vasculitis, rheumatoid
pachymeningitis, sarcoidosis, and chronic cerebral vascular stasis or accidents. 13- 26 IHCP has also been associated
with chronic dialysis, 27 undifferentiated connective tissue
disease, 14 and hydrocephaly with myocarditis, raising the
question of an autoimmune mechanism linking IHCP with
myocarditis. 28
Unique features in our patient include radiographic evidence of a mass effect in the absence of structural lesions,
association with PMR, absence of cranial nerve involvement, and rheumatoid nodulelike lesions noted on brain
and lung biopsies in the absence of rheumatoid arthritis
(RA) or serological evidence of rheumatoid factor and
antinuclear antibodies. Rheumatoid nodules of the brain
and leptomeninges are a rare finding and have only been
reported in patients with deforming RA 29 or nondeforming RA. 30 Brain involvement is generally recognized histologically by the formation of rheumatoid nodules. 31 ·32
Cheng and colleagues33 reported the clinical, laboratory, radiographic, and pathological features of 37 patients
diagnosed with IHCP during an 8-year period and found
that the most common etiologies were sarcoidosis (31%)
and metastatic adenocarcinoma (25% ). The specific etiology remained undetermined in 44% of patients in their
series. Their study indicated that MRI is the preferred
neuroimaging modality, that a biopsy of an enhancing lesion is likely diagnostic, and that a posterior fossa or pterional approach gives the greatest diagnostic yield. Mamelak et al 2 reported 3 patients with IHCP and noted that
headache and cranial nerve findings were the most common symptoms occurring in 100% and 78% of patients
respectively. Masson et al 15 reported 7 patients with IHCP
whose primary clinical findings were headache, ataxia, and
cranial nerve palsies. Their CSF analysis revealed variable
inflammatory changes without evidence of microorgan-

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...• .. -·
• \

Fig 5.

(A ) Section of brain with overlying leptomeninges that
are marked ly t hickened and f ibrotic. Multiple g ranulomas with
chronic inf lammatory infilt rate and f ocal areas of necrosis are
seen. No m icroorganisms w ere ident if ied with speci al stains (H&E,
original m agnification x 40 before 88% reductio n). (B) M ediumpower magnification confirms leptomeningeal t hickening with
prominent ch ronic inflammatio n and scattered giant cells. Underlying brain revea ls marked react ive changes (H&E, origi nal magnification x 100 before 88% red uct io n) (C) Hig h-power view of
the granuloma illustrates necrosis in t he center of t he g ran uloma
(lower left corner), with palisading epit helioid histiocytes and lymphocytes. A sing le, large multi nucleated giant cell is seen in t he left
upper corner (H&E, original magnification x 400 before 58%
reduction).

isms or malignancy. Histological examination of the leptomeninges in 5 patients revealed a cellular infiltrate of
polymorphic cells without epithelioid granuloma. Four of
these patients responded to corticosteroid therapy. A
study 1 of 49 patients with IHCP followed for 12 years
found that in 15% of patients an etiology, usually malignancy, was eventually identified. The most useful empiric
therapy in this group was also corticosteroids. In general,
an initial clinical response to corticosteroid therapy is expected to occur in as many as 50% of patients, 1 despite
subsequent progression of the disease. 2 Combination
therapy with corticosteroid and cyclophosphamide has
been used successfully when Wegener's granulomatosis
was the etiology of IHCPY Spontaneous resolution has
also been reported 34 but is not the usual course.
We believe this patient illustrates the first reported association between IHCP and PMR with evidence of mass
effect and rheumatoid nodulelike lesions in the CNS in the
absence of RA, rheumatoid factor, or antinuclear antibodies. High-dose corticosteroid therapy reversed her focal
neurological symptoms and led to resolution of the mass
effect. Although patients with AD may develop focal findings as part of the natural progression of the disease, ad226

Journal of Neuroimaging Vol 8 No 4 October 1998

ditional pathological processes such as vascular, infectious, neoplastic, and, as in this patient, inflammatory
diseases can be expected to develop in some of these patients. Clinicians need to remain alert to the development
of focal or atypical features in patients with dementia.

References
1. Smith JE, Aksamit Jr AJ. Outcome of chronic idiopathic
meningitis. Mayo Clin Proc 1994;69:548-556
2. Mamelak AN, Kelly WM, Davis RL, Rosenblum ML. Idiopathic hypertrophic cranial pachymeningitis. R eport of
three cases. J Neurosurg 1993;79:270-276
3. Kadoya C, Soejima T, Yamada H, Yokota A. Pachymeningoencephalitis: case report. Neurosurgery 1993;33:131 - 134
4. Murai H, Kira J , Ko bayashi T, et al. Hypertrophic cranial
pachymeningitis due to Aspergillus flavus. Clin Neurol
Neurosurg 1992;94:247-250
5. Berenguer J , Diaz-Mediavilla J, Una D, Munoz P . Central
nervous syste m infection caused by Pseudallescheria boydii: case report and review. Rev Infect Dis 1989;11:890-896
6. Carli P, Yao N, Marlier S, et al. Febrile cervicalgia caused
by Streptococcus milleri external pachyme ningitis. Presse
Med 1993;22:33 (Letter)
7. Bucy PC, Freeman W. Hypertrophic spinal pachymeningitis. J Neurosurg 1952;15:22-27
8. Nishioka R , Nakajima S, Morimoto Y, et al. Hypertrophic

cranial pachymeningitis with Propionibacterium acnes detected by dural biopsy. Rinsho Shinkeigaku 1995;35:526530
9. Leiberman A, Tovi F, Hirsch M. Pachymeningitis presenting features of posterior sinus infection. Eur J Pediatr
1986; 144:583-585
10. Kawano Y, Kira J. Chronic hypertrophic cranial pachymeningitis associated with HTL V-I infection. J Neurol
Neurosurg Psychiatry 1995;59:435-437
11. Gorell JM, Palutke W A, Chason JL. Candida pachymeningitis with multiple cranial nerve pareses. Arch Neural
1979;36:719-720
12. Taveras MJ. Neuroradiology. New York: Williams &
Wilkins, 1996:738
13. Ranoux D, Devaux B, Lamy C, Mear JY, Roux FX, Mas
JL. Meningeal sarcoidosis, pseudo-meningioma, and pachymeningitis of the convexity. J Neural Neurosurg Psychiatry
1992:55:300-303
14. Fujimoto M, Kira J, Murai H, eta!. Hypertrophic cranial
pachymeningitis associated with mixed connective tissue
disease; a comparison with idiopathic and infectious pachymeningitis. Intern Med 1993;32:510-512
15. Masson C, Henin D, Hauw JJ, eta!. Cranial pachymeningitis of unknown origin: a study of seven cases. Neurology
1993;43:1329-1334
16. Larnaout A, Haddad M, Hentati F, Ben Hamida M. Candida albicans meningitis and neurosarcoidosis. Rev Neural
(Paris) 1992;148:762-766
17. Ghilain S, Delreux V, Kevers L, Sindic CJ, Mathurin P,
Laterre EC. Multiple cranial nerve involvement associated
with tentorial pachymeningitis of granulomatous type.
Acta Neural Belg 1988;88:91-100
18. Stern BJ, Krumholz A, Johns C. Sarcoidosis and its neurological manifestations. Arch Neural 1985;42:909-917
19. Radziwill A, Weder B. Neurosarcoidosis of the central
nervous system. Analysis of the long term follow-up of 8
cases. N ervenartz 1995 ;66:915-922
20. O'Duffy JD, Goldstein JP. Neurologic involvement in
seven patients with Bechet's disease. Am J Med 1976;61:
170-178
21. Olson ME, Chernik NL, Posner JB. Infiltration of the lep-

tomeninges by systemic cancer. Arch Neural 1974;30:122137
22. Moore PM, Calabrese LH. Neurological manifestations of
systemic vasculitides. Semin Neural 1994;14:300-306
23. Caselli RJ, Scheithauer BW, O'Duffy JD. Chronic inflammatory meningoencephalitis should not be mistaken for
Alzheimer's disease. Mayo Clin Proc 1993;68:846-853
24. Gutman L, Hable K. Rheumatoid pachymeningitis. Neurology 1963; 13:901-903
25. Pou SA, Maso E, Roquer J. Isolated angiitis of the central
nervous system. Clinical and neuropathological study of 2
cases. Rev Neural (Paris) 1995;151:258-266
26. Eguchi K, Kodama Y, Hotta T, eta!. A case of cranial
hypertrophic pachymeningitis with intracranial hemorrhage. No To Shinkei 1996;48:475-480
27. Feringa ER, Weatherbee L. Hypertrophic granulomatous
pachymeningitis causing progressive blindness in a chronic
dialysis patient. J Neural Neurosurg Psychiatry 1975;38:
1170-1176
28. Tanaka M, Suda M, Ishikawa Y, Fujitake J, Fujii H, Tatsuoka Y. Idiopathic hypertrophic cranial pachymeningitis
associated with hydrocephalus and myocarditis: remarkable steroid-induced remission of hypertrophic dura mater.
Neurology 1996;46:554-556
29. Bathon JM, Moreland LW, DiBartolomeo AG. Inflammatory central nervous system involvement in rheumatoid
arthritis. Semin Arthritis Rheum 1989;18:258-266
30. Karam NE, Roger L, Hankins LL, Reveille JD. Rheumatoid nodulosis of the meninges. J Rheumatol 1994;21:19601963
31. Markenson JA, McDougal JS, Tsairis P. Rheumatoid meningitis: a localized immune process. Ann Intern Med 1979;
90:786-789
32. Kim RC, Collins GH. The neuropathology of rheumatoid
disease. Hum Pathol 1981;12:5-15
33. Cheng TM, O'Neill BP, Scheithauer BW, Piepgras DG.
Chronic meningitis: the role of meningeal or cortical biopsy. Neurosurgery 1994;34:590-595
34. Nishio S, Morioka T, Togawa A, et a!. Spontaneous resolution of hypertrophic cranial pachymeningitis. Neurosurg
Rev 1995;18:201-204

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