Rheumatology International

, Volume 28, Issue 7, pp 713–718 | Cite as

Idiopathic hypertrophic cranial pachymeningitis treated by oral methotrexate: a case report and review of literature

  • T. BosmanEmail author
  • C. Simonin
  • D. Launay
  • S. Caron
  • A. Destée
  • L. Defebvre
Open Access
Case Report


Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a rare clinical entity, characterized by a chronic inflammation causing thickening of the dura. Adequate therapeutic management is still a matter of debate. We present a patient with an IHCP, non-responsive to corticotherapy. Oral methotrexate was introduced (12.5 mg weekly) and total remission was observed after 6 weeks, both clinically and after neuro-imaging. We conclude that methotrexate can be effective and a therapeutical option in patients with IHCP who are resistant to corticotherapy or present major side-effects of chronic corticosteroids use.


Chronic Migraine Giant Cell Arteritis Cranial Nerve Palsy Intracranial Hypotension Carotid Artery Occlusion 
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Hypertrophic pachymeningitis (HP) is a rare clinical entity of diverse aetiology causing thickening of the dura. It was first described by Charcot and Joffroy regarding spinal meninges in 1869. These early reports of hypertrophic pachymeningitis were related to tuberculosis or syphilis [1]. Naffziger described the first case of idiopathic hypertrophic cranial pachymeningitis (IHCP) [2].

Compression of anatomic structures by the meninx, thickened by inflammatory infiltration is the most important cause of the clinical features. These include headache, cranial nerve palsies and ataxia [3, 4, 5, 6, 7, 8, 9].

Several other causes have been recognized, including infections, autoimmune disorders and neoplasms. When an exhaustive evaluation fails to reveal a cause, IHCP is considered. IHCP is a very rare disorder that affects predomininantly male patients. Adequate therapeutic management is still a matter of debate. Several therapeutic strategies have been proposed, including steroids and other immunosuppressive agents, as well as radiotherapy and surgical removal of the affected tissue [10].

In this case report, we present a patient with an IHCP and his responsiveness to oral methotrexate.

Case report

A 62-year-old male consulted in 2002 about a bi-temporal, non-throbbing headache, jaw claudication and diffuse articular pains. He described episodes of transitory hemianopsia. Neurological examination showed no signs of focalisation. He had no history of clinical signs or symptoms of systemic collagen vascular disease, syphilis, tuberculosis or obvious metastatic cancer. Laboratory test showed an erythrocyte sedimentation rate (ESR) of 91 mm and a C-reactive protein of 104 mg l−1 (normal < 3.2 mg l−1). Brain MRI study and biopsies of both temporal arteries were negative. After introduction of oral corticotherapy (prednisone 1 mg kg−1 day−1) an immediate (less than 24 h) and total remission was observed. His neurologist concluded the disease as a giant cell arteritis. In the following years, multiple attempts were made by his physician to reduce his corticotherapy. With daily doses of less than 30 mg the headache and the inflammatory syndrome reappeared.

A few months before his admission to our hospital the patient presented with recurring headaches, different from the headaches of 2002. He described intense occipital, non-throbbing headaches and cervical pain. The inflammatory syndrome worsened (ESR 100 mm). This exacerbation was accompanied by a lingual hypoesthesia and an important photophobia. Attempts to control this aggravation by intensifying his corticotherapy (80 mg daily) were unsuccessful.

He was admitted in our hospital in November 2005. At this time neurological examination showed a 4th, 5th and 12th left cranial nerve paresis and paresthesia of the left leg. The rest of the clinical examination was normal. Opthalmologic examination showed glaucoma as a complication of his chronic corticotherapy. Blood analysis revealed an ESR of 60 mm and a C-reactive protein level of 55 mg l−1. Brain MRI revealed a diffuse thickening and enhancement of the pachymeninges along both sides of the tentorium (Fig. 1).
Fig. 1

Axial (a) and coronal (b) T1-weighted contrast-enhanced MR images show markedly thickened and enhanced dura extending from the vertex to the tentorium

All known causes of pachymeningitis were explored. Blood analyses of rheumatoid factor, complement activation, antineutrophilic cytoplasmic antibodies (ANCA), antinuclear antibodies and tumour markers were normal. Cerebrospinal fluid (CSF) analyses revealed discrete pleiocytosis (white blood cell count 23 mm−3 and elevated protein levels 1.33 g l−1, normal value 0.6–1 g l−1) but the virologic, parasitologic and bacteriologic analyses were negative. PCR assay for the detection of Mycobacterium tuberculosis DNA was negative. Carcinomatous cells were not detected in two CSF samples. Angiotensin converting enzyme was slightly elevated (2.2 UI L−1, interval 0.5–1.50). Chest CT and MRI, bronchial fibroscopy with biopsy, gallium scintigraphy, neurophysiologic explorations presented no arguments for a systemic disease. Investigation for a neoplasia (tumour markers, chest and abdominal CT and bone scintigraphy) was negative. C-reactive protein continued to rise (115 mg L−1) and a significant worsening of the patient’s general condition was noted with a weight loss of 8 kg in 3 months. A control MRI study confirmed the worsening of the diffuse thickening of the dura (Fig. 2).
Fig. 2

Axial (a) and coronal (b) T1-weighted contrast-enhanced MR images show progression of dural thickening corresponding with the clinical worsening at the time of the biopsy

A meningeal biopsy was performed which showed an inflammatory infiltration, locally granulomatous but non-specific. No signs of vasculitis, neoplastic cells or infectious agents were found.

With these exhaustive clinical and para-clinical investigations being negative, we concluded at an IHCP. At that moment the patient was still treated with 60 mg of prednisone daily.

Because of his resistance to chronic steroid therapy, IV methylprednisone was administered (1 g day−1 for 3 days) and oral methotrexate 12.5 mg weekly was started. Total remission of the clinical and biologic abnormalities was evident 6 weeks after introduction of methotrexate as long as there was a progressive reduction of corticotherapy. He regained 7 kg in the following weeks. No side effects were noted. A control MRI study, performed 6 weeks after introduction of methotrexate, demonstrated a practically total abolition of the dural enhancement (Fig. 3).
Fig. 3

Axial (a) and coronal (b) T1-weighted contrast-enhanced MR images obtained 6 weeks after introduction of methotrexate show regression of dural thickening and enhancement

Currently, after 10 months of follow-up (after introduction of methotrexate), the patient is doing well and his corticotherapy is continually reduced. He recovered for his glaucoma and had no side effects for methotrexate. He currently takes 15 mg of oral methotrexate weekly and 12.5 mg cortisone daily and continues to reduce his corticotherapy. ESR and C-reactive protein remain normal. However he continues to describe facial paresthesias. Our therapeutic strategy is to lower the cortisone dosage until 10 mg daily and after a stable condition (clinically and biologically) of minimum 6 months, we will try to lower the methotrexate dosage.


Our patient presented with IHCP, which was confirmed by neuroimaging and biopsy, and which improved with the association of corticosteroids and methotrexate. Since the introduction of CT and MRI, IHCP has been increasingly reported in recent literature. The clinical picture can be heterogeneous. Parney et al. [11] described headache, cranial nerve palsy and ataxia in 88, 62 and 32% of the cases, respectively. Cranial nerve palsies are due to compression of the exit zone of the nerve roots by the hypertrophic basal pachymeningitis. Riku and kato [12] described two patterns of the multiple cranial neuropathies depending on the site of dural inflammation: cavernous sinus to superior orbital fissure involvement and falcotentorial to posterior fossa dural involvement. The headache is probably related to the dural inflammation because in many cases no evidence of raised intracranial pressure was present. Recently, the headache profile was described by Wang et al. [13] and characterized as a chronic daily headache, often resembling chronic migraine. Our patient also described daily headache, but the headache did not resemble chronic migraine. Rarely, IHCP has been reported to lead to internal carotid artery occlusion, venous sinus occlusion and obstructive hydrocephalus [14, 15, 16, 17, 18].

Hypertrophic pachymeningitis can be divided into two types: secondary, in which there is an identifiable coexisting cause and idiopathic, in which no identifiable cause, as in our patient. IHCP is thus a diagnosis of exclusion. Differential diagnoses are extensive. In our case, we performed a diagnostic work-up based on all known causes in current literature [10]. Most authors consider intracranial hypotension, infections, systemic autoimmune disorders, malignancy and meningioma as the main aetiologies of enhanced dura mater on gadolinium MRI.

Although by definition no cause is found for IHCP, different abnormalities are described. In a series of 12 patients, Kupersmith et al. described an elevated ESR in 41%. The chemistry of CSF was variable and non-diagnostic, but protein was elevated in 50% of their patients. They recommend biopsy of the dura when the patient clinically deteriorates or the neuro-imaging worsens, despite treatment [10]. Until now the pathogenesis of IHCP remains unclear. The close relationship to autoimmune disorders such as Wegner’s granulomatosis, rheumatoid arthritis or other connective tissue diseases has been described. Recently p-ANCA positive HP has been reported. As p-ANCA antibodies have been detected in many vasculitides, microvasculitis may be involved in some cases of IHCP [19].

Neuroimaging plays a key role in the evaluation of IHCP. Nevertheless, image study of IHCP can remain negative for 2 years before there is any significant finding [20]. The MR images show a diffusely thickened dura, usually isointense on T1-weighted slices that enhances strongly after paramagnetic contrast injection due to an inflammatory reaction of the pachymeninges. On T2-weighted imaging, the dura appears commonly hyperintense, rarely hypointense related to fibrosis process. The use of gadolinium is important for the evaluation of the pattern of meningeal enhancement that may differentiate between pachy- and lepto-meningitis. MRI can also demonstrate areas suitable for biopsy. In our case, the MRI was normal in the beginning. Although there was an evident change in symptomatology of disease progression, the possibility remains that the symptoms diagnosed as a giant cell arteritis in 2002 was the initial presentation of an occult IHCP.

As mentioned above, the role of the dural biopsy is important in the diagnostic process but even more important is to exclude other causes of HP. Taken into account the high number of relapses reported in literature, biopsy in an early disease stage must be discussed. Non-specific inflammatory changes in the dura are common histopathologic features. Vasculitis or granulomatous changes have been described as well [19].

In our case report angiotensin converting enzyme levels in CSF were elevated and although no other argument was found, neurosarcoidosis must be discussed in our patient. Although the biopsy performed in our patient did not find elements in favour of neurosarcoidosis, we must admit that chronic immunosuppressive therapy can mask the results.

In recent literature there is no consensus on the adequate management of IHCP. Spontaneous resolution of both clinical symptoms and signs, and dural thickening has been reported [21]. A variety of therapeutic approaches have been tried alone or in combination. Corticosteroid therapy is often effective in ameliorating the symptoms and signs, and in stopping the disease progression [22]. In those who do not respond to steroids or those who develop steroid dependence, other immunosuppressive therapies have been used [23].

Most authors agree that corticotherapy should be the first approach in IHCP. Some authors describe only a partial effectiveness of corticosteroid therapy, with partial clinical improvement and relapse when tapering the dosage [10]. Table 1 gives an overview of the therapeutic trials since 1990. Searching the pubmed database in the English-language literature for patients with IHCP receiving treatment, we identified a total of 60 patients. The most frequently used treatment was steroid therapy (n = 56, 93%). Thirty-nine patients were treated with corticosteroids as monotherapy (65%). In this subgroup,18 patients experienced relapses (46%). Different add-on therapeutic options are proposed; six patients received azathioprine, one patient cyclophosphamide, one patient underwent surgery and two patients were treated with methotrexate. In all these patients receiving add-on therapy, a sustained remission was described, permitting to stop or reduce the daily dose of corticosteroids. Considering occult tuberculosis, one patient was empirically treated with antitubercular medication as monotherapy. Surgical excision is sometimes necessary for patients with mass effect due to thickening of the skull base [19]. Symptomatic hydrocephalus sometimes requires ventriculoperitoneal shunting. In the identified patient group, five were operated, one after therapeutic failure of the corticotherapy. Recently the use of low-dose pulse subcutaneous methotrexate was proposed as monotherapy. Total remission of the clinical and neuro-imaging abnormalities was evident after 6 months [24, 25, 26, 27, 28, 29, 30, 31, 32].
Table 1

Therapeutic options: an overview of the literature






Hamilton et al. [24]



Corticosteroid + Aza (N = 2)

Remission with after addition Aza

Mtx + chloroquine (N = 1)

No improvement with Mtx


Remission after addition chloroquine

Masson et al. [25]



Corticosteroid (N = 4)

Improvement but corticodependent

Radiotherapy (= 1)

No lasting improvement

Corticotherapy + Aza (N = 1)

Permitting lowering of corticotherapy after introduction of Aza

Botella et al. [26]




Temporary relief

Parney et al. [11]



Antituberculous therapy

Total remission

Nishioka et al. [27]





Hatano et al. [23]



Corticotherapy (N = 4)

Three sustained remissions

Surgery + corticotherapy (N = 1)

Three relapses

Corticotherapy + cyclophosphamide (N = 1)


Yamamoto et al. [28]




Remission after lymphocytapheresis



Dumont et al. [29]



One corticotherapy

Sustained remission

One surgery

Sustained remission

Sylaja et al. [3]



Four corticotherapy

One complete remission


Three partial remission

Lee et al. [5]





Riku et al. [12]



Thirteen corticotherapy

Relapses in 7 patients

One corticotherapy + Aza

Long-term improvement

One surgery


Kupersmith et al. [10]



Twelve corticotherapy

Relapses in 6 patients

Two corticotherapy + Mtx

Reduction of corticotherapy

Two corticotherapy + Aza

Reduction of corticotherapy

Rossi et al. [30]




Three remission


One relapse

Kanemoto et al. [31]





Ruiz et al. [32]



Subcutanous methotrexate

Total remission

Rudnik et al. [33]





PY publication year, N number of patients, Aza azathioprine, Mtx methotrexate

In our patient we chose a low-pulse oral methotrexate scheme of 12.5 mg weekly. Although, large randomized trials are required to prove the efficacy and tolerability of methotrexate at different doses and routes of administration, we noted a spectacular improvement within the 6 weeks following introduction of methotrexate. After introduction of methotrexate we were able to taper the corticotherapy and reduce the side-effects of its chronic use (glaucoma). There is no consensus about the duration of this therapy. After minimum 12 months we will try to stop the methotrexate.


In this patient with an IHCP, methotrexate was a safe and effective treatment, resulting in a total remission after 6 weeks and allowing to reduce corticotherapy. In patients with IHCP which is non-responsive to corticotherapy, or in patients who present major side-effects of their chronic use of corticosteroids, methotrexate seems indicated. However further work is required to determine the place of oral methotrexate in the therapeutic management of IHCP.


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Copyright information

© The Author(s) 2007

Authors and Affiliations

  • T. Bosman
    • 1
    Email author
  • C. Simonin
    • 2
  • D. Launay
    • 3
  • S. Caron
    • 4
  • A. Destée
    • 2
  • L. Defebvre
    • 2
  1. 1.Department of NeurologyLeiden University Medical CentreLeidenThe Netherlands
  2. 2.Department of Neurology and Movement DisordersSalengro Hospital, Lille University Medical CentreLilleFrance
  3. 3.Department of Internal MedicineClaude-Huriez Hospital, Lille University Medical CentreLilleFrance
  4. 4.Department of RadiologySalengro Hospital, Lille University Medical CentreLilleFrance

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