Journal of the Neurological Sciences 367 (2016) 278–283

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Journal of the Neurological Sciences

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Hypertrophic pachymeningitis
Lewis D. Hahn a, Robert Fulbright b, Joachim M. Baehring a,c,⁎
a
Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, United States
b
Department of Radiology, Yale University School of Medicine, New Haven, CT 06510, United States
c
Department of Neurology and Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, United States

a r t i c l e i n f o a b s t r a c t

Article history: Hypertrophic Pachymeningitis (HP) denotes inflammation and thickening of the dura mater that can be idio-
Received 10 December 2015 pathic or secondary to a wide variety of conditions. Clinically, HP can present as debilitating headaches and cra-
Received in revised form 19 May 2016 nial nerve defects but in other cases may be completely asymptomatic. We aimed to determine the relative
Accepted 9 June 2016
incidence of different etiologies of HP and compare their associated imaging findings. Additionally, we sought
Available online 11 June 2016
to compare the clinical features of the underlying syndromes. We retrospectively examined twenty-two consec-
Keywords:
utive cases of HP seen in a single practitioner neurology practice over a ten-year time period. The most common
Hypertrophic pachymeningitis etiologies were idiopathic HP and neurosarcoidosis. No imaging features were completely specific to any etiology.
Dura Nonetheless, idiopathic HP typically demonstrated diffuse regular enhancement whereas neurosarcoidosis was
Enhancement more likely to display a nodular enhancement pattern. Headache and cranial neuropathies were the most com-
mon clinical presentation. HP symptoms were often responsive to steroids but complete responses were rare. HP
is a diagnostic challenge without specific findings on minimally or non-invasive diagnostic studies. Biopsy is often
required and serves as the basis for effective therapy.
© 2016 Published by Elsevier B.V.

1. Introduction 2. Methods

Hypertrophic Pachymeningitis (HP) denotes inflammation and
thickening of the dura mater. Its pathogenesis is diverse [1,2]: systemic
inflammatory diseases associated with HP include sarcoidosis,
Wegener's granulomatosis, Sjogren's syndrome, rheumatoid arthritis,
and IgG4-related disease [3,4]. Infectious etiologies include tuberculosis,
syphilis, and Lyme disease [5,6]. Dural thickening is also seen as a reac-
tive change to tumor in the underlying bone; this must be distinguished
from true neoplastic invasion. It may also be the result of intracranial
hypotension, likely driven by compensatory interstitial edema of the
meninges in response to decreased volume of the CSF space [7]. If no un-
derlying disease process is identified, the condition is labeled idiopathic
HP.
HP remains a diagnostic challenge. Only a few large case series of HP
are available and data on the relative incidence of its various etiologies
are scarce. The primary goals of this study were to determine the rela-
tive incidence of different etiologies of HP and to describe the spectrum
of associated imaging findings.
Abbreviations: HP, hypertrophic pachymeningitis.
⁎ Corresponding author at: Yale University School of Medicine, PO Box 208042, 333
Cedar St., New Haven, CT 06520, United States.
E-mail address: Joachim.baehring@yale.edu (J.M. Baehring).
Cases of HP seen between July 1, 2002 and June 30, 2012 were iden-
tified retrospectively from the case log of a single investigator (JB) in the
Department of Neurology at Yale School of Medicine. Keywords in this
search included pachymeningitis, meningitis, and dura. Criteria for in-
clusion included HP as diagnosed by dural biopsy or thickening and en-
hancement of the dura mater on T1-weighted gadolinium-enhanced
MRI. Patients with dural thickening as a result of intracranial hypoten-
sion, meningioma, or neoplastic pachymeningitis were excluded. Pa-
tient charts were reviewed to obtain clinical history, laboratory data,
pathology reports, treatments, and outcomes.
Laboratory values were perused for the following diagnostic tests:
Cerebrospinal fluid (CSF) protein, CSF glucose, CSF cell count, Erythro-
cyte Sedimentation Rate (ESR), C-reactive protein (CRP), Angiotensin
Converting Enzyme (ACE; serum or CSF), Anti-Nuclear Antibodies
(ANA), Venereal Disease Research Laboratory test (VDRL), Lyme disease
titer, Purified Protein Derivative (PPD) test, Anti-Neutrophil Cytoplas-
mic Antibody (ANCA) screen, Serum Protein Electrophoresis (SPEP),
anti-Ro antibodies, anti-La antibodies, Rheumatoid Factor (RF),
Human Leukocyte Antigen (HLA) B27, and anti-double stranded DNA
(dsDNA) IgG.
The Social Security Death Index was searched for all patients who
have not had regular follow-up to identify those who are deceased.
MRI images taken at presentation were reviewed with a board-cer-
tified neuroradiologist (RF). Enhancement was categorized by location,

http://dx.doi.org/10.1016/j.jns.2016.06.024
0022-510X/© 2016 Published by Elsevier B.V.
 L.D. Hahn et al. / Journal of the Neurological Sciences 367 (2016) 278–283
overall distribution, and the pattern of enhancement. Overall distribu-
tion was categorized as diffuse or focal on the following basis: diffuse
enhancement was defined as a contiguous area N 50% of the area of
one intracranial compartment consisting of the posterior fossa, either
hemisphere, or spanning greater than five vertebral levels. Focal en-
hancement consisted of enhancement spanning b 50% of any given in-
tracranial compartment and included “multifocal” patterns (i.e.
multiple smaller regions of enhancement). The enhancement patterns
were further classified as “nodular,” “irregular,” and “regular.” Enhance-
ment was considered nodular if there was a single or multiple discrete
nodules N0.5 cm in diameter, irregular if there were nodules b 0.5 cm,
and regular if there was no nodularity at all. Descriptive statistics were
used to describe our findings.
3. Results
3.1. Distribution of cases and demographics
The most common diagnosis was idiopathic HP, constituting eleven
(50%) of the twenty-two cases (Table 1). There were six cases (27%) of
neurosarcoidosis, two cases (9%) of Wegener's granulomatosis, and one
case (5%) each of psoriatic arthritis, Vogt-Koyanagi-Harada disease, and
inflammatory pseudotumor.
Patients with idiopathic HP represented the oldest patients in the se-
ries with a mean age of 68 (standard deviation, S.D. 10 years). By com-
parison, the average age was 46 (S.D. 11) for neurosarcoidosis. An
overall female predominance was seen across groups. Overall, 15 of
the 22 patients (68%) in the series were female.
3.2. Imaging features
All cases of HP were initially diagnosed through MRI features that
showed dural thickening and enhancement. Within these changes,
there was much variation of the specific enhancement patterns (Table
2). The posterior fossa was commonly affected in cases of idiopathic
HP (six cases; Fig. 1), but overall, location was quite variable. The
areas affected by neurosarcoidosis were also varied but involved regions
tended to be located caudally, with two cases involving the occipital/
temporal lobe, and three involving the posterior fossa and tentorium
(Fig. 2). Focal involvement of dura was seen in four of six cases, and
the enhancement pattern was nodular in these four cases as well. In
total, four of the twenty-two cases involved the spinal column (Fig. 3).
3.3. Clinical features
Headache and loss of cranial nerve function were the most common
presenting features of HP regardless of etiology (Table 1). Headache was
present in almost half of the cases of idiopathic HP and
neurosarcoidosis; Cranial nerve dysfunction was seen in more than
half of idiopathic HP and neurosarcoidosis cases. In cases of idiopathic
HP, the cranial nerves II and VIII were most often affected, whereas V
and VI were more commonly involved in neurosarcoidosis. A minority
of patients presented with other features such as seizure, ataxia, and
sensory loss. Two cases of idiopathic HP and one case of
neurosarcoidosis were diagnosed in the absence of symptoms.
Laboratory data are summarized in Table 1. Patients with idiopathic
HP and neurosarcoidosis underwent comprehensive laboratory work-
up as described in the Methods section. Patients with idiopathic HP
and neurosarcoidosis had elevated CSF protein and ESR (Table 1). CSF
lymphocytic pleocytosis was also present in three of seven cases of idi-
opathic HP and two of four cases of neurosarcoidosis. Dural biopsy ob-
tained in seven cases showed a variety of inflammatory changes.
Response to therapy varied according to disease process (Table 1).
Of the patients with idiopathic HP, two were initially asymptomatic
and another had spontaneous resolution of headache. One of the
asymptomatic patients returned for follow-up and has remained
279
asymptomatic. The remaining eight patients were treated with steroids;
seven patients responded with symptomatic improvement, but in five
patients, symptoms either recurred or progressed. Three patients were
identified as deceased through the Social Security Death Index. The
age of these patients at presentation was 75–78. Survival following di-
agnosis ranged from 9.9 to 156 months. Six patients have received reg-
ular follow-up with a range of 2.1 to 6.3 years.
The five symptomatic patients with neurosarcoidosis initially were
treated with steroids. Three patients had complete resolution of symp-
toms following steroid taper; two continue on methotrexate mainte-
nance therapy. The two patients with partial responses were
medically noncompliant. One patient had no symptoms related to his
neurosarcoidosis and did not develop any on follow-up.
The patients with HP of other etiologies all initially responded to ste-
roids, but all eventually had recurrence or progression of symptoms.
4. Discussion
HP is a generally regarded as a rare pathologic entity. Existing
knowledge of HP is largely based on small case series describing HP sec-
ondary to a single entity, although larger studies have been published
recently [3,4]. To our knowledge, this is the first series of HP that char-
acterizes consecutive cases of HP diagnosed through imaging findings.
It is also the largest series that provides detailed description of imaging
findings in HP.
4.1. Distribution of cases and demographics
While there are many etiologies for diffuse dural thickening and in-
flammation, we primarily encountered cases of idiopathic HP and HP in
the setting of neurosarcoidosis.
The largest proportion of cases in our series consisted of idiopathic
HP. This finding was similar to the results of Yanekawa and colleagues'
nationwide survey of Japan, which found that 44% of the cases of HP
were idiopathic. A prior study in 1996 focusing on consecutive cases
of dural thickening and enhancement seen on MRI found that only
one case was idiopathic, with the majority either associated with malig-
nancy or intracranial hypotension [1]. Direct comparison to the Japa-
nese study is difficult as ANCA-related HP was recognized as its own
non-idiopathic entity. Recently, investigators have made the distinc-
tions of ANCA-positive [8] and IgG4-related HP [3,4], with evidence
that HP may be a manifestation of systemic disease related to these fac-
tors even in the absence of other disease manifestations. In case reports,
ANCA titers have lowered concurrently with treatment of HP [9]. In this
report, we included a single p-ANCA positive patient in the idiopathic
group, but this designation would be subject to change if future studies
definitively identify ANCA-related HP as a distinct pathologic entity.
Similarly, IgG4-related disease may in fact be responsible for a sub-
stantial number of cases of HP that were previously thought to be idio-
pathic [3]. IgG4 related disease was first described in 2003 and unifies a
set of diseases affecting any organ systems either in isolation or in com-
bination [10]. Diagnosis is determined on the basis of biopsy which
demonstrates three cardinal features of an IgG4 predominant
lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebi-
tis [10]. Unfortunately, biopsy samples in our study were not stained for
the presence of IgG4+ plasma cells and we are unable to definitively
demonstrate whether cases in our series labeled as idiopathic
pachymeningitis are in fact manifestations of IgG4 related disease. Sim-
ilar to ANCA related HP, serum levels of IgG4 has not reliably predicted
the presence of IgG4+ plasma cells on biopsy of dura or other organ
systems [10,11]. CSF IgG4 may be more predictive [12], but this was
not assessed in our set of cases.
CNS involvement of sarcoidosis is typically reported in b10% of cases
[13,14], and among these cases, the MRI pattern of dural thickening and
enhancement is less frequently found [15,16]. Interestingly, no cases of
sarcoidosis were found in the Japanese series [4]. This may reflect the
 280
Table 1
Patient demographics, clinical presentation, laboratory data, treatment, and outcomes.

Diagnosis N Age at Gender Clinical CSF CSF CSF ESR CRP Other Biopsy features Treatment Partial Complete Survival/follow-up Notes
presentation presentation lymphocytic protein glucose elevation elevation laboratory modalities used treatment treatment
±STDEV pleocytosis elevation depression data response response

Idiopathic 11 68±10 7F 4M Cranial nerve 3/7 7/8 2/7 9/11 3/9 ANA+ Lymphoplasmacytic Steroids (8) 7 3 patients 2 patients had no
hypertrophic deficits (6) (1) infiltrate (2) Cyclophosphamide deceased; range follow-up
pachymeningitis Headache (4) p-ANCA+ Dense fibrous tissue (1) 9.9–156 months. 6 1 Patient had
Seizure (1) (1) (1) Azathioprine (1) patients with spontaneous
Ataxia (2) anti-Ro+ Granulomatous Rituximab (1) active follow-up; resolution of HA
Asymptomatic (1) inflammation (1) median 3.3 years, without treatment.

L.D. Hahn et al. / Journal of the Neurological Sciences 367 (2016) 278–283
(2) No range 0.2 to 8.8 2 patients were
positive years asymptomatic at
tests for presentation and
VDRL, were not treated
Lyme, or
TB.
Neurosarcoidosis 6 46±11 5F 1M Cranial nerve 1/4 2/4 0/4 3/5 2/3 Serum Necrotizing Steroids (5) 2 3 5 patients with 2 patients with
deficits (4) ACE granulomatous Methotrexate (3) active follow-up; partial response
Headache (2) elevation inflammation (1) Azathioprine (1) median 3.4 years, were
Dizziness (1) (2) range 2.1 to 6.3 noncompliant with
Asymptomatic CSF ACE years treatment. One
(1) elevation patient was
(1) asymptomatic at
Anti-Ro+ presentation and
(1) was not treated.
Wegener's 2 30, 4 1F 1M Cranial nerve N/A N/A N/A 0/1 0/1 Steroids (2) 2 Patients last seen Laboratory workup
granulomatosis deficits (1) Rituximab (1) 1.4 and 1.8 years was performed at
Headache (1) Infliximab (1) after diagnosis outside hospitals
Methotrexate (1) for both patients
Psoriatic arthritis 1 65 F Headache (1) 1/1 N/A N/A 1/1 0/1 ANA+ Acute and chronic Steroids, 1 Patient last seen
dsDNA+ inflammation with methotrexate 2.4 years after
neutrophils, diagnosis
lymphocytes,
plasma cells; dense
fibrous tissue
Vogt-Koyanagi- 1 58 F Cranial nerve 1/1 1/1 0/1 1/1 0/1 Normal Steroids 1 Patient last seen
Harada deficits lgG4 2.3 years after
Headache diagnosis
Ataxia,
hearing loss,
tinnitus
Inflammatory 1 62 M Thoracic pain N/A N/A N/A 1/1 1/1 P-ANCA+ Mixed polyclonal Surgical cord 1 Patient last seen
urinary anti-Ro+ infiltrate with decompression, 2.2 years after
retention, psammomatous steroids, rituximab diagnosis
lower calcification
extremity
sensory loss
 L.D. Hahn et al. / Journal of the Neurological Sciences 367 (2016) 278–283 281

Table 2
Patient imaging features.

N Location Diffuse vs. focal enhancement “Roughness” of enhancement

Idiopathic HP 11 Posterior fossa (6) Diffuse (9) Regular (9)

Cavernous sinus (2) Focal (2) Irregular (1)
Optic nerve sheath (2) Nodular (1)
Anterior/middle cranial fossa (2)
Global (1)
Unilateral hemisphere (1)
Spinal-lumbosacral and thoracic dura (1)
Neurosarcoidosis 6 Occipital/temporal lobe (2) Focal (4) Regular (2)
Posterior fossa/tentorium (3) Diffuse (2) Nodular (4)
Global spinal (1)
Cavernous sinus (1)
Cerebello-pontine angle (1)
Wegener's granulomatosis 2 Anterior/middle cranial fossa (1) Focal (1) Nodular (1)
Global/upper cervical spine (1) Diffuse (1) Regular (1)
Psoriatic arthritis 1 Parietal lobe Focal (1) Nodular (1)
Vogt-Koyanagi-Harada disease 1 Global Diffuse and focal depending on region Regular and nodular in
different regions
Inflammatory pseudotumor 1 Mid-upper thoracic spine Diffuse (1) Nodular (1)

higher prevalence of sarcoidosis in the United States in comparison to
Japan [17].
A single case report of HP in the setting of Vogt-Koyanagi-Harada
disease was described recently [18] and this report represents the sec-
ond. Inflammatory pseudotumor of the CNS is extremely rare, and
cases with associated HP have only been described in a few case reports
[19–21]. One patient in our series had psoriatic arthritis; while biopsy
demonstrated evidence of acute and chronic inflammation, these find-
ings are nonspecific and it is unclear whether this was a manifestation
of psoriasis or merely coincidental. We were unable to find other report-
ed cases of HP in the setting of psoriatic arthritis.
Our series had no infectious cases of HP. This was somewhat surpris-
ing: while tuberculosis and syphilis are relatively rare, Lyme disease is
endemic to our region. Despite numerous citations in the literature of
neuroborreliosis as a cause of HP, we were only able to find a single spe-
cific case report documenting dural enhancement in the setting of CNS
Lyme disease, although this patient had concurrent vasculitis [22].
In our retrospective case search, we additionally found 11 cases of
neoplastic pachymeningitis; these were excluded as it can be difficult
to distinguish between dural metastasis and reactive dural changes to
adjacent tumor [23], and we did not have sufficient biopsy material to
distinguish between the two possibilities. Dural metastases are infre-
quently studied in comparison to parenchymal and leptomeningeal
metatases, although they have been found in up to 10% of patients
with systemic cancer in autopsy studies [23]. The most frequent under-
lying primary tumors are breast, prostate, lung, and gastric cancers [23,
24]. It is suggested that a continuous patterns of enhancement repre-
sents reactive change rather than dural invasion [25]. The relatively
high incidence of neoplastic HP likely reflects a referral bias as the pri-
mary focus of our clinic is neuro-oncology.
The reasons for a female predominance in our series are unclear.
Other investigators have reported even or male-predominant distribu-
tions [3,4]. Additionally, the average age at presentation of patients

Fig. 1. 79 year old man who presented with blurry vision, hearing loss, and gait instability.
Axial T1-weighted image of the brain demonstrates dural thickening and enhancement of
the posterior fossa with extension into the internal auditory canal. After negative workup,
he was given the diagnosis of idiopathic HP.
Fig. 2. A 38 year old woman complained of progressive neck pain and weakness over the
course of a year. She was dropping objects from her right hand and needed a cane to walk.
In addition, she had difficulty swallowing. MRI revealed a dural based mass lesion arising
from the rostral cervical spinal canal and the posterior fossa. Histopathology
demonstrated non-caseating granulomatous inflammation. T1-weighted axial MR image
with gadolinium.
282 L.D. Hahn et al. / Journal of the Neurological Sciences 367 (2016) 278–283
Fig. 3. Sagittal T1-weighted image with contrast of a 61 year old man presenting with
thoracic pain, sensory loss, difficulty walking, and inability to urinate. Dural thickening
of the thoracic spinal cord results in cord compression and edema. Biopsy subsequently
provided a diagnosis of inflammatory pseudotumor.
with idiopathic HP was sixty-eight, significantly higher than those with
other etiologies and those reported in the literature [2,4].
4.2. Imaging features
A major focus of our study was imaging features given the essential
role which contrast-enhanced MR has in the diagnosis of HP. A variety
of non-inflammatory conditions may also lead to a similar appearance
of thickened, enhancing dura including meningioma, intracranial hypo-
tension, post-surgical change, and chronic subdural hematoma. In many
cases, ancillary findings coupled with clinical history can clearly identify
an etiology; for example, dural thickening/enhancement in combina-
tion with a slumping midbrain in a patient with positional headache
would be clearly identified as intracranial hypotension, whereas sus-
ceptibility artifact on T2-weighted images in a patient with history of
prior trauma would identify a patient with chronic subdural hematoma.
Once other etiologies have been excluded, imaging in itself cannot be
used to discern between different etiologies of hypertrophic
pachymeningitis; therefore definitive diagnosis relies on biopsy. As
was the case in this study, biopsy is often avoided given its inherent
risks and sufficient clinical suspicion to warrant empiric treatment.
Although there was significant overlap in imaging findings of HP
secondary to all etiologies, our results raise the possibility that location
and pattern of dural enhancement may aid in distinguishing between
underlying etiologies of HP. Idiopathic HP generally exhibited diffuse,
regular enhancement that most commonly involved the posterior
fossa. Thickening of the falx and tentorium has previously been reported
to be the most common finding of idiopathic HP and this was also seen
in our series [26]. Cavernous sinus involvement is also common [2,26].
Both regular and nodular patterns have been seen in prior series [2,
26]. One prior study found an association between poor prognosis and
focal, uneven enhancement, but prognosis in our series could not be
correlated to imaging pattern [27].
In contrast, most neurosarcoidosis cases showed a focal, nodular en-
hancement pattern. As with cases of idiopathic HP, the posterior fossa
was also commonly involved. While this study focused on
neurosarcoidosis with exclusive dural involvement, it is important to ac-
knowledge that other patterns such as leptomeningeal neurosarcoidosis
are much more common [15,16].
4.3. Clinical features
Presentation of HP most frequently included headache and symp-
toms of cranial nerve deficits. Headache and cranial nerve dysfunction
are also well-documented presentations of idiopathic HP [2] and
neurosarcoidosis [15,28,29]. The most frequent cranial nerve deficit
has been reported to be the facial nerve in neurosarcoidosis and the
vestibulocochlear nerve in idiopathic HP, although almost every cranial
nerve has been reported to be involved in both [2,29,30]. In our series,
cranial nerve II and VIII were most frequently involved. Trigeminal
and abducens nerve deficits were most frequent among cases of
neurosarcoidosis. Interestingly, several cases of HP were incidental find-
ings and the patients were otherwise asymptomatic.
ESR was unsurprisingly elevated for all causes of HP, reflecting the
inflammatory nature of HP and its underlying conditions. CRP was less
consistently elevated. CSF analysis showed elevated protein in almost
all cases of idiopathic HP and most cases of neurosarcoidosis. Elevated
CSF protein is frequently documented in both of these entities [15,28,
31]. When CSF leukocytosis was found, there was always lymphocytic
predominance, which is typical of neurosarcoidosis and idiopathic HP
[27,29]. CSF abnormalities generally are inconsistent features of
neurosarcoidosis and the other disease entities; in neurosarcoidosis,
one third of patients show no CSF abnormalities [29,32].
Serum biomarkers were elevated for rheumatologic cases of HP but
no marker was especially sensitive. Both serum and CSF ACE were in-
consistently elevated in our series; while CSF ACE is accepted as a
more reliable marker of neurosarcoidosis than serum ACE, it has lower
sensitivity [15,33]. Several patients with idiopathic HP were positive
for rheumatologic disease markers; however, they lacked systemic
manifestations of these diseases and therefore we preserved the label
of idiopathic disease. Similarly, anti-Ro and p-ANCA were positive for
the patient with inflammatory pseudotumor, but this patient lacked
systemic manifestations of Wegener's granulomatosis and Sjogren's dis-
ease. As discussed above, ANCA and IgG4-related disease may in fact ac-
count for some of the cases of idiopathic HP.
The only patients who were documented as deceased by the end of
our study were idiopathic HP patients; the cause of death for these pa-
tients is unknown, but normal aging likely played a role given that
these patients were age 75 or older at diagnosis.
In cases of idiopathic HP, steroids almost invariably led to temporary
but never sustained improvement in symptoms. By contrast, steroid use
combined with maintenance-dose immune modulating therapy led to
sustained remission of symptoms in compliant neurosarcoidosis pa-
tients. These findings are consistent with past reports [2,34]. Steroid
use in the other inflammatory conditions also led to improvement of
symptoms, though symptoms either recurred or were not fully
suppressed.
As mentioned above, HP in itself is not always symptomatic. Two pa-
tients with idiopathic HP and one with neurosarcoidosis were asymp-
tomatic at presentation and remained asymptomatic on follow-up;
additionally, two of these patients showed imaging resolution of HP
on MRI. Therefore it is unlikely that asymptomatic HP merits pre-
emptive treatment.
4.4. Limitations of study/future directions
Our series, which spanned nine years of time for a single practition-
er, demonstrates that HP is not an uncommon finding and future series
or population-wide studies are indicated. Larger studies will be needed
to make statistically sound comparisons of HP due to varying etiologies.
Our conclusions also primarily compare HP diagnosed based on imaging
findings, and future studies based on biopsy-proven HP are needed to
confirm these findings.
The results of our study may overestimate the frequency of idiopath-
ic pachymeningitis as biopsy specimens were not studied to determine
whether cases labeled as idiopathic may actually be due to IgG4 related
 L.D. Hahn et al. / Journal of the Neurological Sciences 367 (2016) 278–283
disease. Similarly, one p-ANCA positive patient was included in the idi-
opathic hypertrophic pachymeningitis group, but it is controversial
whether such cases are truly idiopathic.
5. Conclusions
HP is a reactive inflammatory process affecting the dura mater that is
identified by thickening and enhancement of the dura mater on con-
trast-enhanced MRI or chronic inflammatory changes seen on dural bi-
opsy. In our series, HP was most commonly idiopathic but also
associated with systemic inflammatory diseases. Location and pattern
of abnormal dural enhancement may help distinguish between etiolo-
gies of HP. Laboratory studies generally show markers of systemic in-
flammation, but we found no markers specific to each underlying
entity. Steroids and other anti-inflammatory agents are useful for reduc-
ing symptoms secondary to HP, but complete remission is rare.
Financial disclosures
No financial disclosures.
Funding
No independent source was used to fund this project.
References
[1] Y. River, A. Schwartz, J.M. Gomori, D. Soffer, T. Siegal, Clinical significance of diffuse
dural enhancement detected by magnetic resonance imaging, J. Neurosurg. 85
(1996) 777–783.
[2] M.J. Kupersmith, V. Martin, G. Heller, A. Shah, H.J. Mitnick, Idiopathic hypertrophic
pachymeningitis, Neurology 62 (2004) 686–694.
[3] Z.S. Wallace, M.N. Carruthers, A. Khosroshahi, et al., IgG4-related disease and hyper-
trophic pachymeningitis, Medicine (Baltimore) 92 (2013) 206–216.
[4] T. Yonekawa, H. Murai, S. Utsuki, et al., A nationwide survey of hypertrophic
pachymeningitis in Japan, J. Neurol. Neurosurg. Psychiatry (2013).
[5] M.J. Thurtell, A.B. Keed, M. Yan, T. Gottlieb, J.M. Spies, G.M. Halmagyi, Tuberculous
cranial pachymeningitis, Neurology 68 (2007) 298–300.
[6] S. Rossi, F. Giannini, A. Cerase, et al., Uncommon findings in idiopathic hypertrophic
cranial pachymeningitis, J. Neurol. 251 (2004) 548–555.
[7] L.M. Shah, L.A. McLean, M.E. Heilbrun, K.L. Salzman, Intracranial hypotension: im-
proved MRI detection with diagnostic intracranial angles, AJR Am. J. Roentgenol.
200 (2013) 400–407.
[8] D. Jacobi, F. Maillot, C. Hommet, et al., P-ANCA cranial pachymeningitis: a case re-
port, Clin. Rheumatol. 24 (2005) 174–177.
[9] T. Horino, T. Takao, Y. Taniguchi, Y. Terada, Hypertrophic pachymeningitis with
MPO-ANCA-positive vasculitis, Clin. Rheumatol. 29 (2010) 111–113.
[10] T. Kamisawa, Y. Zen, S. Pillai, J.H. Stone, IgG4-related disease, Lancet 385 (2015)
1460–1471.
283
[11] M. Ezzeldin, A. Shawagfeh, V. Schnadig, R.G. Smith, X. Fang, Hypertrophic spinal
pachymeningitis: idiopathic vs. IgG4-related, J. Neurol. Sci. 347 (2014) 398–400.
[12] E. Della-Torre, L. Galli, D. Franciotta, et al., Diagnostic value of IgG4 indices in IgG4-
related hypertrophic pachymeningitis, J. Neuroimmunol. 266 (2014) 82–86.
[13] E.E. Lower, K.L. Weiss, Neurosarcoidosis, Clin. Chest Med. 29 (2008) 475–492 (ix).
[14] R.P. Baughman, A.S. Teirstein, M.A. Judson, et al., Clinical characteristics of patients in
a case control study of sarcoidosis, Am. J. Respir. Crit. Care Med. 164 (2001)
1885–1889.
[15] V. Terushkin, B.J. Stern, M.A. Judson, et al., Neurosarcoidosis: presentations and
management, Neurologist 16 (2010) 2–15.
[16] J.K. Smith, M.G. Matheus, M. Castillo, Imaging manifestations of neurosarcoidosis,
AJR Am. J. Roentgenol. 182 (2004) 289–295.
[17] T. Morimoto, A. Azuma, S. Abe, et al., Epidemiology of sarcoidosis in Japan, Eur.
Respir. J. 31 (2008) 372–379.
[18] H.J. Han, H.Y. Kim, J.H. Park, E.J. Lee, G. Kim do, D.I. Shin, Magnetic resonance imaging
of pachymeningeal enhancement in Vogt-Koyanagi-Harada disease, Neurol. Sci. 31
(2010) 785–788.
[19] K. Matsumoto, Y. Natori, E. Hirokawa, T. Iwaki, Hypertrophic pachymeningitis as a
result of a retropharyngeal inflammatory pseudotumor: case report, Neurosurgery
51 (2002) 1061–1064 (discussion 1064-1065).
[20] P.C. Lui, Y.S. Fan, S.S. Wong, et al., Inflammatory pseudotumors of the central ner-
vous system, Hum. Pathol. 40 (2009) 1611–1617.
[21] A.H. Cho, B.H. Lee, K.W. Kwak, J.K. Kang, Inflammatory pseudotumor of temporal
bone with pachymeningitis, cranial neuropathies and uveitis, Eur. Neurol. 51
(2004) 238–240.
[22] J. Oksi, H. Kalimo, R.J. Marttila, et al., Intracranial aneurysms in three patients with
disseminated Lyme borreliosis: cause or chance association? J. Neurol. Neurosurg.
Psychiatry 64 (1998) 636–642.
[23] L. Nayak, L.E. Abrey, F.M. Iwamoto, Intracranial dural metastases, Cancer 115 (2009)
1947–1953.
[24] F. Laigle-Donadey, S. Taillibert, K. Mokhtari, J. Hildebrand, J.Y. Delattre, Dural metas-
tases, J. Neuro-Oncol. 75 (2005) 57–61.
[25] J. Ahmadi, D.R. Hinton, H.D. Segall, W.T. Couldwell, Surgical implications of magnetic
resonance-enhanced dura, Neurosurgery 35 (1994) 370–377 (discussion 377).
[26] Y.C. Lee, Y.C. Chueng, S.W. Hsu, C.C. Lui, Idiopathic hypertrophic cranial
pachymeningitis: case report with 7 years of imaging follow-up, AJNR Am. J.
Neuroradiol. 24 (2003) 119–123.
[27] O.Y. Bang, D.I. Kim, S.R. Yoon, I.S. Choi, Idiopathic hypertrophic pachymeningeal le-
sions: correlation between clinical patterns and neuroimaging characteristics, Eur.
Neurol. 39 (1998) 49–56.
[28] E. Hoitsma, C.G. Faber, M. Drent, O.P. Sharma, Neurosarcoidosis: a clinical dilemma,
Lancet Neurol. 3 (2004) 397–407.
[29] F.G. Joseph, N.J. Scolding, Neurosarcoidosis: a study of 30 new cases, J. Neurol.
Neurosurg. Psychiatry 80 (2009) 297–304.
[30] A.N. Mamelak, W.M. Kelly, R.L. Davis, M.L. Rosenblum, Idiopathic hypertrophic cra-
nial pachymeningitis. Report of three cases, J. Neurosurg. 79 (1993) 270–276.
[31] A. Rojana-udomsart, T. Pulkes, K. Viranuwatti, J. Laothamatas, S. Phudhichareonrat,
R. Witoonpanich, Idiopathic hypertrophic cranial pachymeningitis, J. Clin. Neurosci.
15 (2008) 465–469.
[32] V. Oksanen, Neurosarcoidosis: clinical presentations and course in 50 patients, Acta
Neurol. Scand. 73 (1986) 283–290.
[33] G.A. Christoforidis, E.M. Spickler, M.V. Recio, B.M. Mehta, MR of CNS sarcoidosis: cor-
relation of imaging features to clinical symptoms and response to treatment, AJNR
Am. J. Neuroradiol. 20 (1999) 655–669.
[34] A. Rudnik, D. Larysz, J. Gamrot, A. Skorupa, G. Bierzynska-Macyszyn, P. Bazowski, Id-
iopathic hypertrophic pachymeningitis - case report and literature review, Folia
Neuropathol. 45 (2007) 36–42.