The document discusses neuroimaging findings in Wegener's granulomatosis. Key findings include: 1) Pachymeningeal enhancement on MRI, which can indicate direct invasion of tissues or non-contiguous "metastatic" disease. 2) White matter lesions and infarctions on MRI/CT, related to possible ischemic effects of vasculitis. 3) Discrete parenchymal granulomas seen as enhancing lesions on MRI. 4) Pituitary abnormalities like enhancement and enlargement indicating involvement.

1. INDEX
 INTRODUCTION
 NEUROIMAGING FINDINGS IN
WEGENER'S
GRANULOMATOSIS
 DISCUSSION
INTRODUCTION
WG is a systemic disease characterized by the triad of granulomatous lesions of the upper
and lower respiratory tract, focal segmental glomerulonephritis, and disseminated
necrotizing vasculitis. Clinical features are detailed in Table 1. Most patients present with
symptoms and signs referable to the upper respiratory tract, and most will have concurrent
evidence of lower respiratory tract involvement, sometimes subclinical. This is now
referred to as initial phase or limited disease. After a median delay of 5 months, the
systemic phase of the disease appears, marked by systemic necrotizing vasculitis,
preferentially involving small arterioles, capillaries and post-capillary venules, and
crescenteric glomerulonephritis, with rapid progression to renal failure.

2. Table 1. CLINICAL FEATURES OF WEGENER'S GRANULOMATOSIS
Male: female ratio 1.2:1
Age range (mean)(years) 9-83(41-50)
Signs and Symptoms
 Fever (%) 50
 Anorexia and weight loss (%) 35
 Sinusitis (%) 61-85
 Otitis media 32-42
 Eye manifestations (orbital pseudotumor, 41-52
episcleritis, scleritis, uveitis, retinitis [%])
 Cough (%) 20-28
 Pleuritis (%) 67
 Nodules/infiltrates on chest radiograph 11-30
 Hemoptysis (%) 45
 Skin lesions (palpable purpura, papules, 67
vesicles, ulcers, nodules
 Arthralgias/arthritis (%) 29
 Neurologic manifestations 15
 Peripheral nervous system 8
 Central nervous system (%) 39-45
 System Involvement
 Respiratory tract
o Upper (%) 90

3. o Lower (%) 48-85
 Renal (%) 77
 Eye (%) 39-52
Neurologic involvement (Table 2) may occur in any phase of the disease, and particular
neurologic features reflect the particular pathologic process involved: direct invasion of
paranasal and para-aural tissues by the granulomatous process, "metastasis" of the
granulomatous process to sites within the CNS that are not contiguous with the upper
airways, and necrotizing vasculitis. Direct invasion of the orbit and temporal bone appears
to account for orbital pseudotumor with associated involvement of extraocular muscles, the
optic and oculomotor nerves, and deafness caused by labyrinthine involvement-as well as
destruction of the seventh and eighth cranial nerves; however, most cranial nerve palsies,
as well as pituitary damage, appear to reflect granulomatous basilar meningitis, reflecting
"metastatic disease" that is not contiguous with disease of the upper airways. This
pachymeningitis can extend well up over the cerebral convexity or along the falx or
tentorium and can account for "cerebritis" associated with seizures and focal neurologic
deficits. (1) It may also involve the spinal canal, producing myelopathy. Vasculitis offers the
best explanation for peripheral neuropathy, which, like the neuropathy of PAN, is
characteristically a mononeuritis multiplex. Vasculitis also offers a plausible explanation of
ischemic stroke and intracerebral and subarachnoid hemorrhage (rare), and has been
pathologically demonstrated in a number of cases.
Table 2. NEUROLOGIC MANIFESTATIONS OF WEGENER'S GRANULOMATOSIS,
Drachman, 5 Nishino et al, 6
 Exophthalmos 12 %
 Any cranial neuropathy 6 %
 Ophthalmoplegia 3-5 %
 Optic nerve or chiasm involvement 7 %
 Pituitary involvement, diabetes insipidus 4 %
 Cranial nerve VII palsy 4%
 Vestibular involvement or deafness 3 %
 Involvement of base of brain, meninges 7 %
 Cerebrovascular events 4%
 Ischemic stroke 3%
 Venous thrombosis 1%
 Intracerebral hemorrhage 3%
 Subarachnoid hemorrhage 2%
 Cerebritis 1.5%
 Seizures 3%

4.  Neuropathy 16%
o Mononeuritis multiplex 13%
o Polyneuropathy 8%
 Myopathy 4%
 Etiology and Pathogenesis
The etiology of WG remains uncertain; however, a number of observations implicate
ANCA, in conjunction with intercurrent infection, in the pathogenesis. The proposed
mechanism is as follows: infection leads to the production of cytokines such as interleukins
1 and 8 and tumor necrosis factor alpha, which cause neutrophils to express adhesion
molecules (leading them to stick to vascular endothelium), and to express proteins that
provide the targets for ANCA (proteinase 3 and myeloperoxidase, among others).
Circulating ANCA then binds to these proteins and induces neutrophil degranulation,
generation of oxygen-free radicals, and endothelial cell injury. The presence of ANCA,
regardless of the specific underlying disease, is strongly associated with the human
leukocyte antigens (HLA) allele DQB*0301. By this mechanism, infection might potentiate
disease activity in WG, and there is compelling empirical evidence that this occurs.
 Diagnosis
Despite the peculiar and seemingly pathognomonic nature of the WG clinical triad, the
often prolonged initial phase of the disease and its some- what protean nature provide the
basis for a broad differential diagnosis, which includes many other vasculitides; relapsing
polychondritis; lethal midline granuloma (nasopharyngeal disease, which may be caused by
a limited and locally aggressive form of WG, B-cell lymphoma, and a limited form of
lymphomatoid granulomatosis, also termed polymorphic reticulosis, actually a T-cell
lymphoma); systemic lymphomatoid granulomatosis; sarcoidosis; eosinophilic pneumonia;
and a host of infectious diseases such as tuberculosis, fungal diseases, syphilis,
rhinoscleroma, and leprosy. Routine laboratory abnormalities (anemia, leukocytosis,
thrombocytosis, low titer rheumatoid factor) are nonspecific. The most helpful serologic
test is an assay for cytoplasm or C-ANCA (related to antibodies to the serine proteinase,
proteinase-3), which is 98% specific, and in active, generalized WG, has a sensitivity of
96%. Sensitivity drops to 65% in initial phase or inactive disease. In contrast,
antiperinuclear or P-ANCA (related primarily to antibodies to myeloperoxidase) is
associated primarily with MPA and AG. Tissue diagnosis (lung, renal, or sural nerve
biopsy) is often necessary.
The diagnosis of WG is strongly supported by the histologic features of granulomatous
inflammation and vasculitis in the resected tissue mass, coupled with the finding of positive
cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA).

5. Figure 1. Wegener granulomatosis. Histologic sections of the dura in a patient with
Wegener’s granulomatosis showed permeation by a dense, diffuse and focally nodular
granulomatous infiltrate composed of histiocytes, lymphocytes, plasma cells, scattered
multinucleate giant cells (arrows), eosinophils and neutrophils. The polymorphous
infiltrate showed no cytologic features of malignancy. In several areas the granulomatous
infiltration is clearly vasocentric and focally small blood vessels showed fibrinoid necrosis
with intramural neutrophils and karyorrhectic debris, and petechial hemorrhage. An
elastic tissue stain (Verhoeff-van Gieson) showed fragmentation of the elastica, confirming
the impression of a vasculitic granulomatous process. Special stains for bacteria,
mycobacteria, and fungi were negative.
NEUROIMAGING FINDINGS IN WEGENER'S GRANULOMATOSIS
 Pachymeningeal Enhancement
In Wegener granulomatosis, the meninges are considered to be abnormal (involved by the
disease) if they showed either diffuse or focal thickening on contrast-enhanced MR images.
Involvement of both the tentorium cerebelli and the dura overlying the convexity of the
cerebrum might occur in combination, however the tentorium cerebelli might be the sole
site of involvement. In Wegener granulomatosis the condition is primarily pachymeningitis
and leptomeningeal involvement by the disease is only very rarely demonstrated. Two
distinct MRI patterns of distribution of meningeal invlovement are noted in Wegener
granulomatosis (See table 3)

6. Table 3. Wegener granulomatosis types
Type Comment
Disease contiguous with  Focal dural thickening and enhancement adjacent and /or
disease of the upper contiguous with orbital, nasal, or paranasal disease. This
airways. represent direct invasion of paranasal and para-aural
tissues by the granulomatous process. Direct invasion of
the orbit and temporal bone appears to account for orbital
pseudotumor with associated involvement of extraocular
muscles, the optic and oculomotor nerves, and deafness
caused by labyrinthine involvement. Focal dural
thickening might be nodular or linear. Nodular dural
thickening might produce a mass that might require
surgical decompression.
Disease not contiguous  Diffusely abnormal meninges unrelated to sinus or orbital
with disease of the disease reflecting "metastatic disease" that is not
upper airways. contiguous with disease of the upper airways. This
pachymeningitis (primarily dural invlovement) can extend
well up over the cerebral convexity or along the falx or
tentorium and can account for "cerebritis" associated with
seizures and focal neurologic deficits. It may also involve
the spinal canal, producing myelopathy. Dural
involvement might be asymmetric or symmetric The dura
overlying the spinal cord might be involved in a similar
fashion. Dural biopsy is diagnostic of Wegener
granulomatosis. Severe headache is the reason for referral
for MR imaging in meningeal involvement.

7. Figure 2. (a) Transverse and (b) coronal T1-weighted contrast-enhanced spin-echo MR
images (500/9) demonstrate diffuse symmetric linear dural thickening and enhancement
(arrowheads).

8. Two distinct patterns of abnormal meningeal enhancement may be observed on intravenous
gadolinium-enhanced MR imaging. Dural (i.e., pachymeningeal) enhancement follows the inner
contour of the calvaria, whereas pial-subarachnoid (i.e., leptomeningeal) enhancement extends
into the depths of the cerebral and cerebellar sulci and fissures. Enhancement surrounding the
brain stem is always of the pial-subarachnoid space type because the arachnoid mater is clearly
separated from the pia by the intervening basal subarachnoid cisterns in this region. Although
leptomeningeal enhancement has been shown to occur more commonly in the setting of
meningitis than with neoplastic involvement, inflammatory and neoplastic processes may appear
similar or identical on imaging studies. A diffuse, thin, regular sheetlike enhancing appearance
over the surface of the brain favors an inflammatory cause, whereas irregular, nodular meningeal
enhancement occurs more commonly, although not exclusively, with neoplastic subarachnoid
dissemination.
Figure 3. (a) Sagittal and (b) transverse T1-weighted contrast-enhanced spin-echo MR
images (500/9) show extensive thickening and enhancement of the dura (arrows) overlying
the thoracic spinal cord.

9. Figure 4. A, Coronal fat-suppressed T1-weighted contrast-enhanced spin-echo MR image
(500/9) demonstrates focal thickening and enhancement of the dura (arrows) overlying the
inferior aspect of both frontal lobes and contiguous with extensive nasal and paranasal
disease. B, Transverse fat-suppressed T1-weighted contrast-enhanced spin-echo MR image
(500/9) shows thickening and enhancement of the dura overlying the anterior left temporal
lobe (arrows) contiguous with extensive paranasal disease.

10. Figure 5. A-C, MR images in a case of Wegener's granulomatosis with intracranial
involvement and meningeal involvement.
Figure 6. Wegener granulomatosis. MRI T1 postcontrast images showing chronic
inflammatory reaction involving the orbital fat , extraocular muscles, and lacrimal gland
(A). Notice leptomeningitis demonstrated as meningeal contrast enhancement with brain
edema (probably due to cerebritis). Biopsy confirmed the diagnosis in this case

11. Figure 7. Wegener granulomatosis, A,B CT scan showing granulomatous infiltration of the
anterior fossa and the nasal cavity and on the mediastinum, C,D,E,F
 Infarcts
Nonhemorrhagic infarcts that affected the cortex, white matter, or both, in a typical
vascular distribution might be seen in Wegener granulomatosis. Multiple infarctions can
occur. Ischemic brain lesions might be related to cerebral vasculitis.
 Nonspecific White Matter Lesions
Nonspecific white matter lesions with high signal intensity on intermediate-weighted and
T2-weighted images are occasionally seen in Wegener granulomatosis. These lesions can be
multiple and are commonly seen in the periventricular, subcortical regions, the basal
ganglia, the mesencephalon and pons. White matter disease - in Wegener granulomatosis-
is probably ischemic in nature.

12. Figure 8. Transverse T2-
weighted fast spin-echo
MR image (3,000/105
[effective]) in a patient
suspected of having
cerebral vasculitis shows
an ill-defined area of high
signal intensity in the
pons (arrows).
 Discrete Parenchymal granulomas
Discrete parenchymal lesions with high signal intensity on intermediate-weighted and T2-
weighted images, low signal intensity on T1-weighted images, and some peripheral
enhancement on gadolinium-enhanced images are occasionally demonstrated in Wegener
granulomatosis

13. Figure 9. Transverse T2-
weighted fast spin-echo
MR image (3,000/105
[effective]) in a patient
with gradual onset of
ataxia shows a discrete
right cerebellar lesion
(arrow) with high signal
intensity. An
intracerebral
granulomatous lesion was
thought to be the most
likely cause because of
the location, gradual
onset of symptoms,
peripheral enhancement,
and improvement in
ataxia and reduction in
the size of the lesion after
treatment.
 Pituitary Abnormalities
Enhancement and/or enlargement of the pituitary gland are occasionally demonstrated in
Wegener granulomatosis. The enhancement is commonly homogeneous with thickening
and / or enhancement of the infundibulum, especially superiorly. The pituitary involvement
can occur by direct invasion of the granulomatous disease from the sphenoidal sinus or
secondary to basal pachymeningitis. Diabetes insipidus can occur when the pituitary gland
is involved.

14. Figure 10. Coronal T1-weighted
contrast-enhanced spin-echo MR
image (500/9) in a patient with
diabetes insipidus shows diffuse
enlargement of the pituitary gland
(straight arrows) with thickening
and enhancement of the
infundibulum (curved arrows).
There also is filling and rim
enhancement (arrowheads) in the
sphenoid sinuses, consistent with
inflammatory disease.
 Cerebral and cerebellar Atrophy
Cerebral atrophy that is more marked than expected given the patients age can be
demonstrated in Wegener granulomatosis. Cerebral atrophy usually ranges from mild to
moderate. Atrophy can also involve the cerebellum. Patients with cerebral atrophy
commonly have symptoms suggestive of cerebral vasculitis, including peculiar intellectual
affect, headaches, confusion, and transient neurologic events such as paraesthesia,
blackouts, and visual loss.

15. Table 4. Types of CNS involvement in Wegener granulomatosis
Type Comment
Pachymeningeal In Wegener granulomatosis, the meninges are considered to be
Enhancement abnormal (involved by the disease) if they showed either diffuse or
focal thickening on contrast-enhanced MR images. Involvement of
both the tentorium cerebelli and the dura overlying the convexity
of the cerebrum might occur in combination, however the
tentorium cerebelli might be the sole site of involvement
Infarcts Nonhemorrhagic infarcts that affected the cortex, white matter, or
both, in a typical vascular distribution might be seen in Wegener
granulomatosis. Multiple infarctions can occur. Ischemic brain
lesions might be related to cerebral vasculitis.
Nonspecific White Nonspecific white matter lesions with high signal intensity on
Matter Lesions intermediate-weighted and T2-weighted images are occasionally
seen in Wegener granulomatosis. These lesions can be multiple and
are commonly seen in the periventricular, subcortical regions, the
basal ganglia, the mesencephalon and pons. White matter disease -
in Wegener granulomatosis- is probably ischemic in nature.
Pituitary Enhancement and/or enlargement of the pituitary gland are
Abnormalities occasionally demonstrated in Wegener granulomatosis. The
enhancement is commonly homogeneous with thickening and / or
enhancement of the infundibulum, especially superiorly.
Cerebral and Cerebral atrophy that is more marked than expected given the
cerebellar Atrophy patients age can be demonstrated in Wegener granulomatosis.
Cerebral atrophy usually ranges from mild to moderate. Atrophy
can involve the cerebellum.
DISCUSSION
In a 1963 literature review of 104 patients with Wegener granulomatosis, Drachman (5)
identified three processes of nervous system involvement. First, vasculitis occurred in 29
(28%) patients and produced mononeuritis multiplex, polyneuritis, myopathy,
intracerebral hemorrhage, subarachnoid hemorrhage, and cerebral arterial or venous
thrombosis. Second, granulomatous lesions resulting from contiguous invasion from nasal,
paranasal, or orbital disease and involving the optic nerve, optic chiasm, pituitary, nasal
vestibule, base of the brain, and meninges were present in 27 (26%) patients. Third,
granulomatous lesions remote from nasal granulomas and involving the meninges, cranial
nerves, brain, and parietal bone were described in four (4%) patients.
Because cerebral and meningeal involvement by Wegener granulomatosis is rare, with a
reported prevalence of 2%–8% (1,4,6), there are few reports of small series (7,8) in which
the MR imaging appearances were described. Asmus et al (7) reported the MR imaging

16. findings in seven patients: Six patients had small, sometimes multiple, focal areas of
increased signal intensity in the white matter on T2-weighted images, and one had an
infarct. Provenzale and Allen (8) reported the computed tomographic (two patients) and
MR imaging (five patients) findings in seven patients, which included dural thickening and
contrast enhancement in three patients, infarcts in two, areas of high signal intensity in the
white matter on T2-weighted MR images in two, and abnormal high signal intensity in the
brainstem on T2-weighted MR images in two. Direct intracranial spread from nasal,
paranasal, or orbital disease or remote, discrete granulomatous lesions in brain
parenchyma were not reported in either series.
Remote granulomatous involvement of the meninges in Wegener granulomatosis is rare (4–
6,10). At postmortem examination in one of 104 patients in Drachman's review (5),
meningeal involvement by a necrotic and granulomatous process was observed. Nishino et
al (6,10) reported that only one of 324 patients with Wegener granulomatosis had
thickening and enhancement of the right tentorium cerebelli, which caused multiple cranial
neuropathies and severe headaches. None of 85 patients described by Fauci et al (4) had
meningeal involvement with Wegener granulomatosis. The typical MR imaging appearance
is that of bilateral diffuse symmetric linear dural thickening and enhancement. Such
findings were described by Provenzale and Allen (8) in three patients, although focal and
nodular thickening have also been previously reported (11). Large areas of high signal
intensity in the white matter underlying thickened meninges on T2-weighted images have
been previously noted (11,12). Diffuse dural thickening and enhancement might occur both
intracranially and overlying the thoracic cord. Spinal dural thickening might produce
myelopathy. There is one previous report (10) of dural thickening overlying the thoracic
cord in a case of Wegener granulomatosis, and this resulted in a subacute myelopathy.
Leptomeningeal thickening and enhancement overlying the sulci in addition to dural
enhancement is quite rare and to our knowledge, this radiologic finding has rarely been
reported, although thickening, fibrosis, and numerous granulomas that often surround the
involved blood vessels, as seen at histologic examination of the pia-arachnoid, have been
reported (11).
The differential diagnosis for diffuse symmetric linear meningeal thickening is broad and
includes neurosarcoid, primary dural tumors such as lymphoma and meningioma,
metastases, infectious meningitis, neurosyphilis, and hypertrophic cranial pachymeningitis.
In neurosarcoid, the pia is involved more frequently than the dura (13). Clinical evaluation
and laboratory and radiologic investigations help the radiologist determine the most likely
diagnosis, although biopsy may be necessary for confirmation.
Direct intracranial invasion from adjacent extracranial disease has been reported (5,14) to
be the most common means by which the central nervous system is involved with Wegener
granulomatosis. This commonly occurs as extensive nasal, paranasal, or orbital disease
spreading intracranially to adjacent dura.
The ability to acquire multiplanar images without irradiating the eyes makes MR imaging
an excellent modality for demonstration of subtle intracranial spread from nasal,

17. paranasal, or orbital disease. Because thickened dura can be difficult to differentiate from
cerebrospinal fluid on T2-weighted images, we advocate the use of fat-suppressed T1-
weighted MR imaging with gadolinium enhancement when direct spread is suspected.
Vasculitis most frequently affects the peripheral nervous system, causing mononeuritis
multiplex or polyneuritis; it involves the brain or meninges in 0%–6% of patients, causing
intracerebral hemorrhage, subarachnoid hemorrhage, and cerebral arterial or venous
thrombosis (4–6). These hemorrhagic complications are thought to be secondary to
weakening of blood vessel walls by means of an inflammatory vasculitis, resulting in vessel
rupture and bleeding. Patients with WG might have symptoms suggestive of vasculitis,
such as altered consciousness or altered affect, or symptoms suggestive of ischemic
episodes, such as paraesthesia, blackouts, or internuclear ophthalmoplegia.
Patients with WG might have nonspecific areas of high signal intensity were seen in the
white matter on intermediate-weighted and T2-weighted MR images and most probably
these white matter lesions are ischemic in nature and this is consistent with vasculitic
granulomatous nature of WG. There are several other possible causes of infarct in cases of
Wegener granulomatosis: arterial occlusion secondary to a granulomatous mass that
extends from nasal or paranasal sites into the skull base (15), emboli from marantic
endocarditis (8), infarct secondary to renal failure–induced hypertension, and other causes
unrelated to Wegener granulomatosis.
Remote granulomatous lesions in brain parenchyma are the least common form of central
nervous system involvement with Wegener granulomatosis (5), although there have been a
few reported cases (16–18). Patients may present with seizures, and the lesions may be
single or multiple (17,18). Homogeneous and ring enhancement have been demonstrated,
and the lesions have high signal intensity on T2-weighted MR images and have been shown
to either decrease in size or disappear with treatment (17). Cerebral granulomas have been
found to be dark brown, scarred, indurated, and poorly demarcated at surgery and to
contain plasma cells, lymphocytes, histiocytes, and giant cells at histologic examination
(18).
Multiple nonspecific lesions with increased signal intensity on intermediate-weighted and
T2-weighted MR images are seen in the white matter in many conditions, including
postinfectious encephalitis, viral infections, sarcoidosis, multiple sclerosis, Behçet
syndrome, and the leukodystrophies, and are commonly seen in the elderly. This white
matter pathology might have ischemic aetiology and this is supported by the pathological
impression that granulomatous infiltration in WG is clearly vasocentric (Fig. 1c) and
focally - in white matter lesions- small blood vessels commonly show fibrinoid necrosis with
intramural neutrophils and karyorrhectic debris.
However the exact etiology of white matter lesions in relation to Wegener granulomatosis is
unclear. Similar white matter lesions in cases of Wegener granulomatosis have also been
reported by Provenzale and Allen (8) and Asmus et al (7). Asmus et al reported that these
areas represented areas of microinfarct, and Drachman (5) reported the postmortem
examination finding of small (<4 x 6-mm) areas of infarct in the thalamus, cortex,

18. mesencephalon, pons, and subcortical white matter in a patient with cerebral vasculitis
secondary to Wegener granulomatosis.
The pituitary and infundibulum may be involved in Wegener granulomatosis by means of
distant granulomas or direct spread. Four patients in Drachman's series (5) had
involvement of the pituitary gland due to direct extension from nasal, paranasal, or orbital
disease that caused diabetes insipidus. Czarnecki and Spickler (19) reported a case of
diabetes insipidus and hyperprolactinemia; this was probably secondary to remote
granulomatous involvement with Wegener granulomatosis because there was no evidence
of direct extension from extracranial disease. MR imaging demonstrated a sellar mass,
absence of the posterior pituitary high-signal-intensity spot, and thickening and
enhancement of the infundibulum, with almost complete resolution of findings at repeat
imaging performed 2 months after treatment with high-dose steroid therapy (19). In
general in patients with diffuse enlargement of the pituitary gland and infundibular
thickening, it is impossible to be certain whether this represented distal granulomatous
involvement with Wegener granulomatosis or direct spread from extensive inflammatory
changes in the sphenoid sinus, even when floor of the pituitary fossa appears to be intact in
both patients.
Finally, the exact etiology of brain atrophy in cases of Wegener granulomatosis is unclear,
but possible explanations include cerebral vasculitis, drugs used in treatment (eg, steroids),
and other unrelated causes such as senile atrophy. Yamashita et al (20) reported the
development of cerebral atrophy over 6 months in a patient with cerebral vasculitis
secondary to Wegener granulomatosis.
In summary, in patients with cerebral and meningeal involvement with Wegener
granulomatosis, there is a wide spectrum of MR imaging findings, which reflect the three
means by which the central nervous system can be affected in this disease: vasculitis; direct
spread from adjacent disease in the nasal, paranasal, or orbital region; and remote
granulomatous lesions. MR imaging, with which it is possible to acquire multiplanar
images without radiation, is an excellent modality for demonstration of these
abnormalities, especially for evaluation for direct spread to the meninges from orbital,
nasal, or paranasal disease.
 Treatment of Wegener granulomatosis
The 2-year case fatality rate in untreated WG is 93%. Optimal treatment consists of daily
intravenous or oral cyclophosphamide, 2 mg/kg/day Monthly pulse intravenous
cyclophosphamide, preferred because of its better side-effect profile, is insufficient to
reliably induce remission but may be employed to sustain remission. Cyclophosphamide
treatment is generally maintained through 1 year of stable remission. Daily prednisone, 1
mg/kg/day is routinely employed during the first 6- 12 months. With this approach,
Hoffman et al (1) achieved marked improvement or partial remission in 91 % of patients
and complete remission in 75%. The high morbidity rate associated with this treatment
(infections, hemorrhagic cystitis, secondary neoplasia) has led to an avid search for
alternative approaches. Methotrexate is successfully employed to induce remission in

19. patients who present with relatively more indolent disease and may be effective in
sustaining remission. Cotreatment of patients on cyclophosphamide regimens with
trimethoprim-sulfamethoxazole (Bactrim, Septra) significantly reduces the rate of relapse.
Initially, WG was uniformly fatal within a few months of diagnosis; the prognosis was
minimally improved after institution of steroid therapy.
Cyclophosphamide has since been used very effectively and is the usual drug of choice for
induction of remission. The well-recognized toxicity of oral cyclophosphamide has lead to
institution of pulse therapy as the present standard of care.
Azathioprine may be used as maintenance therapy or as initial therapy in patients unable
to tolerate cyclophosphamide.
Less frequently employed therapies include methotrexate. Excellent remission is achieved
in about 70% of patients but unfortunately relapses are common. Aggressive treatment of
pulmonary and renal involvement at the time of disease onset seems to lessen the
probability of later neurologic involvement.
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The author
Professor Yasser Metwally
www.yassermetwally.com