alexa Seronegative Wegenerand#195;and#162;and#194;and#8364;and#194;and#8482;s Granulomatosis Presenting as a Multiple Cranial Neuropathy | OMICS International
ISSN: 2329-6895
Journal of Neurological Disorders
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Seronegative Wegener’s Granulomatosis Presenting as a Multiple Cranial Neuropathy

Sara Machado1*, Amélia Nogueira Pinto2, Nuno Inácio1, Filipe Paulas3, Luísa Biscoito4, João Paulo Farias5, Marta Amaral3 and José Alves3
1Department of Neurology, Hospital Professor Doutor Fernando Fonseca, EPE. Amadora, Portugal
2Institute of Neurology, UCL, National Hospital for Neurology and Neurosurgery. London, UK
3IV Department of Internal Medicine, Hospital Professor Doutor Fernando Fonseca, EPE. Amadora, Portugal
4Department of Neurorradiology, Hospital de Santa Maria, Centro Hospitalar de Lisboa Norte EPE. Lisboa, Portugal
5Department of Neurosurgery, Hospital de Santa Maria, Centro Hospitalar de Lisboa Norte EPE. Amadora, Portugal
Corresponding Author : Sara Machado
Neurology Department
Hospital Professor Doutor Fernando Fonseca
EPE, IC-19 Amadora, Portugal
Tel: +351 214348404
E-mail: [email protected]
Received February 18, 2014; Accepted March 12, 2014; Published March 15, 2014
Citation: Machado S, Pinto AN, Inácio N, Paulas F, Biscoito L, et al. (2014) Seronegative Wegener’s Granulomatosis Presenting as a Multiple Cranial Neuropathy. J Neurol Disord 2:149. doi: 10.4172/2329-6895.1000149
Copyright: © 2014 Machado S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Related article at
DownloadPubmed DownloadScholar Google

Visit for more related articles at Journal of Neurological Disorders

Abstract

Wegener’s granulomatosis (WG) is an immune-mediated systemic vasculitis of unknown etiology that can be seen in almost any system. It classically affects the upper and lower airways, lungs and kidneys. Despite its possibility of generalization, neurological involvement is hardly seen. When it occurs, WG tends to affect the peripheral nervous system, often as sensory-motor polyneuropathy or mononeuritis multiplex. Involvement of cranial nerves is much less frequent, and the most affected is the optic nerve. Involvement of the central nervous system is even rarer but there are reports including cerebrovascular events, seizures, cerebritis, diabetes insipidus and pachymeningitis. In 1990, four criteria have been identified for the clinical diagnosis of WG by the American College of Rheumatology, which are still in effect and include upper airways inflammation, pulmonary nodules and microhematuria. A patient who meets at least 2 of the criteria may be diagnosed as having classical WG with a sensitivity of 88% and a specificity of 92%. Usually there is positivity for antineutrophil cytoplasmatic antigene (ANCA) but its absence does not exclude this diagnosis, especially when the clinical picture is highly suggestive. We present a case of palsy of the lower cranial nerves as the initial presentation of a seronegative WG.

Keywords
Wegener’s granulomatosis; Neurological involvement; Cranial neuropathy; Aseptic meningitis
Summary
Wegener’s granulomatosis (WG) is an immune-mediated systemic vasculitis of unknown etiology that can be seen in almost any system. It classically affects the upper and lower airways, lungs and kidneys. Despite its possibility of generalization, neurological involvement is hardly seen. When it occurs, WG tends to affect the peripheral nervous system, often as sensory-motor polyneuropathy or mononeuritis multiplex [1]. Involvement of cranial nerves is much less frequent, and the most affected is the optic nerve [1]. Involvement of the central nervous system is even rarer but there are reports including cerebrovascular events, seizures, cerebritis, diabetes insipidus and pachymeningitis [2].
In 1990, four criteria have been identified for the clinical diagnosis of WG by the American College of Rheumatology [3], which are still in effect and include upper airways inflammation, pulmonary nodules and microhematuria. A patient who meets at least 2 of the criteria may be diagnosed as having classical WG with a sensitivity of 88% and a specificity of 92%. Usually there is positivity for antineutrophil cytoplasmatic antigene (ANCA) but its absence does not exclude this diagnosis, especially when the clinical picture is highly suggestive [4,5].
We present a case of palsy of the lower cranial nerves as the initial presentation of a seronegative WG.
Case Report
A 59 years old woman was in her usual state of good health until October 2009. She presented in the emergency room with one month history of severe right otalgy followed by an indolent and progressive appearance of homolateral facial palsy, gait disturbance, dysphagia and dysphonia. There was low grade fever since the beginning, without other accompanying symptoms. She had previously been treated with antibiotic (ceftriaxone 1 g IM for 2 weeks) and oral steroid (deflazacort up to 30 mg PO for 7 days) with no recovery. On the neurological examination we found peripheral type paresis of the VII, IX, X and XIth right cranial nerves, and the rest of the examination was unremarkable. Also, there were no significant signs in the general examination namely adenopathies or cutaneous abnormalities.
Since there was a paresis of the lower cranial nerves, the syndromic diagnosis of Vernet Syndrome was done, and a lesion in the jugular foramen was suspected. A brain MRI was performed and found out a round mass in the expected location, with homogeneous enhancement after the use of gadolinium, and also a right mastoiditis. The MRA supported a possible jugular glomus (Figure 1). In this context, a conventional angiography was realized and the hypothesis of glomus was not confirmed, but an occlusion of the right internal jugular vein was identified. The presumptive diagnosis a jugular vein thrombosis due to a right otomastoiditis was assumed. However, taking into account the age of the patient, further investigation was made to exclude prothrombotic states or occult neoplasy.
The laboratory evaluation disclosed a modest elevation of ESR (45 mm) and CRP (3.07 mg/dl), leucocytosis without neutrophilia (11,700/ μl) and an urinalysis showed mild microhematuria (52.8/μl). The prothrombotic screening which includes an auto-immune evaluation was completely normal (including ANA and ANCA). Renal US and CT scan did not find any anatomic abnormalities or signs of medical nephropathy. A thoracic CT scan found multiple millimetric bilateral pulmonary nodules, interpreted as metastasis. A comprehensive search for a primary lesion was performed with several exams but without any positive results: tumoral markers, mammography and mammary US and PET scan. CSF analysis including cytology, bacterial and viral antibody detection (such as antibodies against varicella zoster and herpes simplex I and II virus and against mycoplasma and borrelia burgdorferi), immune screening (including ANA, ANCA and ECA), oligoclonal bands and cultures (namely for mycobacterium tuberculosis) were normal.
During the hospital stay there was a spontaneous but subtle improvement. She was discharged with acetylsalicylic acid 150 mg PO and then seen in regular visits in both Neurology and Oncology outpatient clinics. In April 2010, she returned to our department with a week course of severe headache which was refractory to NSAIDs and difficulty in the verbal articulation de novo. On the examination there was only a XIIth right cranial nerve palsy with no meningeal signs or other remarkable deficits. A MRI was performed and the previous right mastoiditis and ipsilateral mass in the jugular foramen both persisted and a new adjacent meningeal enhancement was found (Figure 2). A second lumbar puncture was done, with a normal opening pressure, but this time with pleocytosis (42 cells, mononuclear). Apart from these finding, the LCR analysis was normal once again (with all the evaluations previously described).
Based on the upper and inferior airways, renal and CNS involvement plus the absence of any abnormal values of immune marker as ANCA, the diagnosis of seronegative granulomatous vasculitis was likely and the patient was referred to the systemic immunomediated diseases outpatient clinic. Corticotherapy was then initiated with three IV pulses of methylprednisolone followed by a month course of prednisolone 1 mg/kg PO. All the clinical symptoms disappeared, a MRI was repeated with no meningeal enhancement, and the LCR evaluation was entirely normal. As this case represented a disseminated form of Wegener’s Granulomatosis, we initiated the treatment with cyclophosphamide. There were administrated 7 cycles, 3 of 500 mg and 4 of 450 mg IV, with an exceptional clinical recovery. The control MRI showed a decrease of the primary lesion and no enhancement after gadolinium (Figure 3). The controle chest CT scan found only 2 of the previous micronodules and both the urinary sediment and the ER normalized. After the suspension of this drug, azathyoprine was started but due to gastrointestinal intolerance, mycophenolate mophetil was finally initiated. She is currently taking 500 mg PO tid. After 13 months of treatment she remains completely asymptomatic without any abnormalities in the neurological examination.
Discussion
WG is a multisystemic granulomatous disease that usually begins with a localized inflammation of the nasal mucosa, lung tissue and kidneys and may subsequently involve other systems as the nervous system. The presence of cranial nerves involvement is not common but can develop in 6.5% of cases [5]. To our knowledge, cranial nerve palsies without previously diagnosis of WG is very rarely seen in the literature and lower cranial nerve palsies when present, may be associated with a skull-base pachymeningitis [6,7]. The aim of this report is to draw physician’s attention to the high possibility of unusual presentations of WG.
This entity should thus be considered in cranial multiple neuropathies or aseptic meningitis when there is also renal and respiratory tract involvement. In our case, these clues were all present: cranial neuropathy and inflammatory changes in the CSF not explained by other inflammatory disorders (namely sarcoid) or infections (such as borreliosis), as well as the renal and pulmonary abnormalities.
Although ANCA positivity is a sensitive and specific marker or WG, it is not currently part of the disease classification and the seronegativity should not exclude this diagnosis and delay the prompt initiation of treatment. This patient had symptomatic improvement after treatment with prednisolone and cyclophospamide.
It’s early diagnosis and treatment is of paramount importance as it is well known that without therapy it is uniformly fatal, being its 1-year mortality 80%. Corticosteroids and cytotoxic agents as cyclophosphamide are the mainstay of treatment and have significantly improved the natural course of the disease [8,9]. Prompt recognition and immunosuppressive therapy can have a major impact on the ominous course of the disease.
 
References









Figures at a glance

image   image   image
Figure 1   Figure 2   Figure 3
Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

Article Usage

  • Total views: 11916
  • [From(publication date):
    March-2014 - May 21, 2018]
  • Breakdown by view type
  • HTML page views : 8103
  • PDF downloads : 3813
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

business[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
Leave Your Message 24x7