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

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 [14‐18].

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 [24‐32].

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.