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Presentations and outcomes of neurosarcoidosis: a study of 54 cases

S. Pawate, H. Moses, S. Sriram
DOI: http://dx.doi.org/10.1093/qjmed/hcp042 449-460 First published online: 20 April 2009

Abstract

Objective: To report on the clinical presentations, laboratory abnormalities, treatment and outcomes in 54 patients with neurosarcoidosis (NS).

Background: Sarcoidosis is an inflammatory granulomatous disease affecting multiple organ systems. Neurosarcoidosis (CNS involvement) is seen in approximately 25% of patients with systemic sarcoidosis, although it is subclinical in most of these cases. Because of its rarity, exposure of neurologists to the clinical spectrum of NS is limited to case reports or short case series.

Patients and Methods: A database of 3900 patients treated at the Vanderbilt Multiple Sclerosis Clinic between 1995 and 2008 was searched for ‘neurosarcoidosis’, ‘neurosarcoid’, ‘sarcoidosis’ and ‘sarcoid’. Of the 162 patient records that were retrieved, 54 patients were found to meet the criteria for definite, probable or possible neurosarcoidosis and were reviewed, including their clinical presentation, Cerebrospinal fluid (CSF) findings, Magnetic resonance imaging (MRIs), biopsy results, treatment, and where available, outcomes 4 months to 20 years after onset of the presenting illness.

Results: Clinical presentations and imaging findings in NS were varied. Cranial nerve abnormalities were the most common clinical presentation and involvement of the optic nerve in particular was associated with a poor prognosis for visual recovery. Isolated involvement of lower cranial nerves had a more favorable outcome. T2 hyperintense parenchymal lesions were the most common imaging finding followed by meningeal enhancement. Long-term treatment consisted of prednisone and/or other immunomodulators (azathioprine, methotrexate or mycophenolate mofetil).

Conclusions: Unlike systemic sarcoidosis, there is difficulty in making tissue diagnosis when involvement of CNS is suspected. MRI and CSF studies are sensitive in the detection of CNS inflammation but lack specificity, making the ascertainment of neurosarcoidosis a clinical challenge. In addition the low prevalence of the disease makes clinical trials difficult and therapeutic decisions are likely to be made from careful reporting from case studies.

Introduction

Sarcoidosis is a multisystem inflammatory granulomatous disease of unknown etiology although current opinion favors an immune response to an as yet unknown antigen.1 The incidence of sarcoidosis in North America is estimated at 3–10 per 100 000 among Caucasians and 35–80 per 100 000 among African Americans.2 Although the characteristic non-caseating granulomas can occur in any organ system, the lungs and the draining mediastinal lymph nodes are the most common sites of involvement.3,4 Neurosarcoidosis (NS), i.e. sarcoidosis involving the nervous system, is thought to be much rarer occurring in less than 5% of patients with systemic sarcoidosis, although post-mortem studies suggest that the incidence of NS may be higher than current estimates.5–7 Isolated NS without systemic involvement is thought to represent 17% of NS.8

Since there is no definitive test for sarcoidosis the diagnosis relies on clinical suspicion, along with attendant laboratory, imaging and pathological abnormalities. Zajicek et al.9 established a diagnostic classification system for neurosarcoidosis that distinguished ‘definite’, ‘probable’ and ‘possible’ NS based on tissue evidence of non caseating granulomas and supportive evidence of sarcoid pathology in laboratory and imaging studies (Table 1).

View this table:
Table 1

Classification of definite, probable and possible NS (modified from ref.9)

Neurosarcoidosis can be diagnosed in patients with (i) a clinical presentation suggestive of neurosarcoidosis with (ii) exclusion of other possible diagnoses, as follows:
1. Definite NS: Positive central nervous system histology
2. Probable NS: [a] Laboratory evidence of CNS inflammation (elevated levels of CSF protein and/or cells, the presence of oligoclonal bands and/or MRI evidence compatible with neurosarcoidosis), and [b] Evidence for systemic sarcoidosis (either through positive histology, including Kveim test, and/or at least two indirect indicators from Gallium scan, chest imaging and serum ACE)
3. Possible NS: Where the above criteria are not met

Because of its rarity, exposure of neurologists to the clinical spectrum of NS is limited to case reports or short case series. Only one large series has been published in North America over the last 10 years and it examined the outcome of accepted therapies.10 We report the clinical presentation of NS in 54 patients and provide a follow up of these patients from 4 months to 20 years providing a natural course of patients with neurological involvement. We have also included representative case reports and provide the readership of the spectrum of presentation and course of neurosarcoidosis.

Methods

A database of 3900 patients treated at the Vanderbilt Multiple Sclerosis Clinic between 1995 and 2008 was searched for patient records containing the text words ‘neurosarcoidosis’, ‘neurosarcoid’, ‘sarcoidosis’, or ‘sarcoid’. Of the 164 patient records that were retrieved, 110 did not have a diagnosis of neurosarcoidosis. A total of 54 patients were found to meet the criteria for definite, probable or possible neurosarcoidosis and were reviewed, including their clinical presentation, CSF findings, MRIs, biopsy results, treatment, and where available, outcomes 4 months–20 years after onset of the presenting illness. Statistical correlations were done using Prism software (Graphpad software version 3.02).

Results

Patient demographics

The group of 54 patients comprised 40 women and 14 men (Supplementary table). The age at presentation was 40.8 years ±11.6 years (range 12–66). The follow-up period was 5 ± 4.4 years (range 4 months to 20 years).

Classification of patients according to Zajicek criteria

In 9/54 of the patients the diagnosis was made based on pathological evidence of noncaseating granulomas in the CNS (definite neurosarcoidosis). Interestingly, only one of the nine patients had known systemic sarcoidosis prior to their neurological disease and therefore in 8/9 cases of definite NS, CNS manifestation was the initial presentation. In four of nine patients with definite NS, chest imaging showed no pulmonary sarcoidosis. A total of 33/54 patients were classified as probable NS. Fifteen of the 33 had known pre-existing systemic sarcoidosis, whereas in the remaining 18, systemic sarcoidosis was recognized during the workup of their neurological symptoms. In 12/54 patients, the diagnosis of ‘possible neurosarcoidosis’ was made by the authors after exclusion of other possibilities in appropriate clinical settings. In 7/12 possible NS patients, (patients 43–49, Supplementary table), there was no evidence of pulmonary sarcoidosis but evidence from CSF and MRI studies suggestive of NS. In three patients (patients 50–52, Supplementary table), there was imaging evidence of pulmonary sarcoidosis in a clinical setting consistent with NS, but there was no biopsy evidence or a second indirect evidence such as increased serum ACE level to satisfy criteria for probable NS. In the remaining 2 patients, there was normal chest imaging (patient 53) or unavailable chest imaging (patient 54) in the presence of CSF or MRI evidence of CNS inflammation consistent with NS.

Clinical presentation

Subacute loss of central vision with retrobulbar pain was the most common clinical presentation of optic neuritis and was seen in 19 of 54 (35%) patients (Table 1). In 13 patients (24%) the involvement of optic nerve was bilateral which occurred in close temporal sequence. Lower cranial nerve involvement was seen 12/54 (23%) patients, which included facial nerve involvement in 6/54 (11%) patients and hearing loss due to 8th nerve involvement (5/54 patients, 9%). Thirteen patients (24%) presented with myelopathy manifesting as weakness and/or sensory abnormalities of arm and legs. The remaining presentations are noted in Table 2.

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Table 2

Initial clinical presentations of NS

Presenting symptomNumber of patients (%)
Number of patients in the study54
Bilateral ON13 (24%)
Myelopathy10 (19%)
Seizures9 (17%)
Headache9 (17%)
Unilateral ON6 (11%)
Facial nerve palsy6 (11%)
Hearing loss5 (9%)
Other cranial neuropathy5 (9%)
Encephalopathy2 (4%)
Ataxia2 (4%)
Vertigo1 (2%)
Panhypopituitarism1 (2%)
Peripheral Neuropathy1 (2%)
Total (some patients had more than one initial symptom)70
  • Cranial neuropathies were the commonest manifestation of NS, occurring in 35 of the 54 patients (63%). Of the cranial neuropathies, optic neuropathy was the commonest, affecting 35% of patients while facial nerve involvement was seen in 11%. Myelopathy, presenting with sensory and motor symptoms in the upper or lower extremities, was seen in 19%. Seizures (17%) and headaches (17%) were other features seen in 10% or more of the patients in this series.

Magnetic resonance imaging

MRIs of brain were available in 53 of the 54 patients, and spinal cord MRIs in 18 of the 54 (Table 3, Supplementary table). The only person who did not have a brain or spinal cord MRI (patient 34) had an implanted cardiac defibrillator. Intraparenchymal T2 hyperintense lesions were the most common finding on brain MRI (Figure 1). Gray matter T2 hyperintense were seen in 6/53 of our patients (Figure 1). The T2 hyperintense lesions were contrast enhancing in 12 patients (23%) (Figure 2). Meningeal enhancement following injection of gadolinium was seen in 10 (19%) of patients (Figure 3). Swelling and/or enhancement of optic nerves or chiasm was seen in 5/19 patients who presented with visual loss (Figure 4). An enhancing 8th cranial nerve was seen in one patient. Other imaging presentations included intracranial masses simulating neoplasms in 3/53 (Figures 5 and 6) and vasculitic infarcts in one patient (Figure 7). Brain MRI was normal in 6 of 53 patients. Abnormal cervical or thoracolumbar spine abnormalities, including spinal cord swelling, meningeal enhancement, and parenchymal contrast enhancing lesions were seen 13 of 18 patients (Figures 8 and 9). One patient presented with abnormalities exclusively in the spinal cord (patient 18, described in case 7).

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Table 3

Magnetic resonance imaging results

MRI Brain (available in 53/54 patients)
    T2 hyperintense non-enhancing WM lesions16 (30%)
    Meningeal enhancement10 (19%)
    Contrast-enhancing parenchymal WM lesions10 (19%)
    Normal brain MRI6 (11%)
    Optic nerve and chiasm enhancement or enlargement5 (9%)
    T2 hyperintense non-enhancing GM lesions4 (8%)
    Intracranial mass (tumor-like)3 (6%)
    Contrast-enhancing parenchymal GM lesions2 (4%)
    8th nerve enhancement1 (2%)
    Vasculitic infarcts1 (2%)
    No brain MRI1 (2%)
    Total brain MRIa59
MRI spinal cord (available in 18/54 patients)
    Abnormal13 (72%)
    Normal5 (28%)
  • Brain MRI was available in 53 of the 54 patients (see Supplementary Table for details). T2 hyperintense white matter lesions were the commonest feature, found in 28 patients (52%) and in 10 patients they were contrast-enhancing. Gray matter lesions were found in 6 patients (11%) and were contrast-enhancing in 2. Meningeal enhancement was seen in 10 patients (19%). aSome patients had multiple features on MRI.

Figure 1.

White and gray matter lesions in NS. Subcortical (A) and periventricular (B) regions show extensive white matter lesions. Extensive lesion is also seen in the midbrain (C) and pons (D). There were bilateral thalamic lesions (E) that enhanced after contrast administration (F). (A–E) T2 FLAIR images and (F), postcontrast T1 image. Patient is described in Case 1.

Figure 2.

Enhancing parenchymal nodules in NS. T2 images (A) show nodules with extensive surrounding edema. T1 post-contrast images in axial view (B) show enhancement of the nodules. Patient is described in Case 2.

Figure 3.

Meningeal enhancement in NS. Post-contrast T1 images of the brain, axial (A) and coronal (B) views showing extensive leptomeningeal enhancement in the posterior fossa. Patient is described in Case 3.

Figure 4.

Optic nerve and chiasm involvement in NS. Compared to the pre-contrast images (A and C), after IV contrast administration, there is enhancement of optic nerves bilaterally (B) and of the optic chiasm (D). Patient is described in Case 4.

Figure 5.

Apparent glioma. T2 FLAIR image (A) shows an edematous lesion in the left temporal lobe. Pre- (B) and post- (C) contrast images show contrast enhancement. Biopsy showed the mass to be a sarcoid granuloma. Patient is described in Case 5.

Figure 6.

Extraaxial mass. T2-weighted image (A) shows an extraaxial hypointense lesion that is contrast-enhancing in axial (B and C) and coronal (D) views. The mass occupied the right side of the anterior cranial fossa with extension into the region of the cribriform plate. Posteriorly, the mass extended to the level of the clinoid process on the right and to the sella turcica. There was encasement of the right optic nerve and partial encasement of the left optic nerve. Patient is a 45-year-old woman who presented with visual loss on the right.

Figure 7.

Sarcoid vasculitis. Extensive infarcts in the thalamus (A) and brainstem (B). Patient is described in Case 6.

Figure 8.

Spinal cord lesions in NS. T2 sagittal view (A) and post-contrast sagittal view (B), showing an anteriorly located lesion that extends from T2 to T7. Patient is described in Case 7.

Figure 9.

Longitudinal myelitis. T2-weighted images of cervical (A) and thoracolumbar spinal cord (B) show edema and T2 hyperintensity extending the entire length of spinal cord. Post-contrast images were not available. Patient is a 32-year-old woman who presented with subacute paraparesis and sensory loss in the lower extremities.

Chest imaging

A total of 46/54 (85%) patients had chest X-ray. Abnormalities suggestive of sarcoidosis were present in 28 (61%). In 4/54 only results of chest CT was available and all of them were abnormal and indicative of systemic sarcoid. Ten of the patients with normal CXR had chest CT, which showed evidence of sarcoidosis in two. Combining X-ray and CT, chest imaging showed evidence of systemic sarcoidosis in 34 of the 50 patents (68%). Four patients did not have any imaging studies of the chest.

Biopsy

Tissue diagnosis of sarcoid was available for 36/54 (67%) patients (Supplementary table). In 8/54 patients (15%) brain was biopsied and in one patient a spinal dural nodule was removed. In 23/54 patients (43%) had lung/hilar lymph node biopsies. In the remaining five patients in whom biopsy results were available, lymph node (1), skin (1), testis (1), conjunctiva (2) were biopsied. All biopsies were positive for non caseating granulomas.

CSF studies and ACE levels

CSF results were available in 42/54 (76%) of patients (Supplementary table). ACE levels (Supplementary table) were available from serum in 42 (76%) patients) and CSF ACE was measured in 24/54 (44%) patients (Supplementary table). CSF indicators of NS showed features consistent with non infectious inflammatory changes. An increased CSF protein was seen in 26 of the 42 patients on whom CSF protein was available. Of the 26 patients, 14 had protein higher than 100 mg/dl CSF. Lymphocytic pleocytosis was seen in 24 patients, with seven having more than 100 cells. A decreased CSF glucose level was seen in only seven patients, and in six of these there was meningeal enhancement on MRI and parenchymal enhancement in the seventh. In 8/42 (19%) CSF studies, oligoclonal bands were present.

Treatment and prognosis

A total of 38 patients received steroids as the initial treatment, either as an initial pulse of high dose corticosteroids (IVMP 1 g daily for 3–5 days) (15 patients), or oral steroids (23 patients) followed in many by maintenance steroids. In 11 patients NS was managed with symptomatic treatment alone. Long-term immunosuppression was offered in the remaining 43 patients (Table 4). Immunosuppressive therapies were added and the corticosteroids were reduced or discontinued in 37 patients (Table 4) to avoid systemic complications of long-term steroids. The patients were on the treatments noted, as of their last clinic visit.

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Table 4

Maintenance treatment in the NS patients

Maintenance treatmentNumber of patients
No specific treatment11 (20%)
Methotrexate alone9 (17%)
Prednisone and methotrexate8 (15%)
Maintenance prednisone6 (11%)
Mycophenolate mofetil alone6 (11%)
Azathioprine alone6 (11%)
Prednisone and Mycophenolate mofetil4 (7%)
Prednisone and Azathioprine2 (4%)
Plaquenil and methotrexate1 (2%)
Rituximab1 (2%)
Total54
  • Maintenance immunosuppression was needed in 39 of the patients and consisted of low dose prednisone alone, and/or steroid sparing agents, usually methotrexate, azathioprine or mycophenolate mofetil. In a few cases, other medications were tried for a short time before switching to long-term medications and these have not been included. Symptomatic medications such as anti-seizure medications are also not included.

Patients who presented with bilateral decrease vision due to optic neuropathy (13/54) generally had a poor prognosis (Table 5). Among the 13 patients with bilateral ON, six lost vision (20/200 or worse) in at least one eye, while three others had a vision of 20/50 or worse in at least one eye. Three patients have VA of 20/30 or better in both eyes. Unilateral ON seemed to recover better, with five of the six patients achieving visual acuity of 20/30 or better (Table 5). Among patients with hearing loss, one patient lost hearing completely and received a cochlear implant. One patient recovered hearing to function without aids, and 3 recovered it completely. Other cranial neuropathies resolved completely. No patient showed persistent facial weakness. Among the 12 patients with myelopathy, their clinical symptoms either stabilized or improved. One patient with panhypopituitarism is doing well with hormone replacement. Patients with seizures due to intracranial lesions have been seizure-free on immunosuppression and anti-epileptic medications. Similarly headaches resolved after treatment. Three patients who had evidence of widespread parenchymal or meningeal involvement had poor outcomes (described in case histories 1, 3 and 6).

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Table 5

Outcomes in neurosarcoidosis with ON

PresentingF/U (years)Last recorded visual acuity
Bil ON620/400, 20/30
Bil ON120/40, 20/25
Bil ON520/200, 20/200
Bil ON1020/200, 20/200
Bil ON820/200, 20/25
Bil ON120/70, 20/25
Bil ON420/200, 20/200
Bil ON7LP, 20/20
Bil ON620/30, 20/60
Bil ON420/25, 20/30
Bil ON120/50, 20/50
Bil ON2020/70, NLP
Bil ON620/20, 20/20
R ON, meningioma420/20, 20/20
Seizures, R ON4Died in the acute phase
Bell's, R ON1320/30, 20/25
Myelopathic, L ON620/25, 20/25
L ON320/20, 20/20
L ON1620/15, 20/20
  • In 7 of the 13 patients with bilateral ON, there was a visual acuity of 20/200 or worse in at least one eye. Unilateral ON seemed to recover better with all patients except one who died in the acute phase achieving VA of 20/30 or better.

Discussion

This article describes our experience on the clinical presentation and course of 54 patients with NS at the Vanderbilt Multiple Sclerosis Center. The majority of the referrals were made to the MS center because of concerns that the underlying disease may be MS.

We recognize the limitations of chart review in attempting to describe the clinical features and natural history of sarcoidosis. While we have included the cases that we diagnosed as having possible NS, it is possible that we may have overlooked other cases of possible neurosarcoidosis that did not have evidence of pulmonary sarcoidosis. A limitation of our series is that none of the patients except one (patient 4; described in Case 1) had gallium scans, which can increase the detection of inflammatory granulomas in extrapulmonary sites. Also, none of our patients had the Kveim testing, which is not usually performed in the United States. Marangoni et al.11 proposed deleting the Kveim test, serum ACE and chest X-ray from Zajicek criteria and including high resolution chest CT, bronchoalveolar lavage with a CD4:CD8 ratio of greater than 3.5 and a CSF CD4:CD8 ratio of greater than 5. The CD4:CD8 ratios remain to be validated from other studies. In our experience a normal serum ACE was of no diagnostic value but an increased serum ACE prompted chest imaging to look for pulmonary sarcoidosis. Only in 2 of the 10 cases with normal CXR did chest CT find evidence of sarcoidosis. Therefore CXR remains a valuable initial diagnostic tool.

Our study differs from other case series in the clinical presentations and imaging characteristics. Optic neuritis was the most common presentation in our series, seen in 35% of patients. Spinal cord involvement, which was the most common manifestation in another series reported from a department of medicine,12 was seen in 24% of our patients. Two other case series have reported visual manifestations as the most common presentation of neurosarcoidosis,9,13 and both of these series were from neurology departments. The series by Stern et al.14 that showed facial nerve palsy as the commonest manifestation was reported from a sarcoid clinic. Referral bias probably accounts for the differences in clinical presentations reported in different case series. Thus optic neuritis and myelopathy, two common presentations of multiple sclerosis, resulted in referral to our MS center and are the two most common manifestations of NS in our series.

MRI findings were varied as noted in reviews.15,16 In agreement with Smith et al.,17 intraparenchymal T2 hyperintense lesions were the most common finding. Although basilar meningitis with involvement of cranial nerves is thought to be a common phenomenon,18 evidence of meningeal enhancement following injection of gadolinium was seen in only 10 (19%) of patients. Chest imaging showed evidence of systemic sarcoidosis in 34 of the 50 patents (68%). This is in agreement with Chapelon et al.8 and Salazar et al.19 and indicates that chest imaging has a high diagnostic yield in suspected NS and helps to establish the presence of systemic sarcoidosis. CSF findings in NS are nonspecific and include an increased protein and cell count9 which along with MRI evidence of CNS inflammation, aid in the diagnosis of NS.

There is controversy regarding the utility of ACE levels in making the diagnosis of NS.20–22 In our series, normal ACE levels were of limited value and increased serum or CSF ACE levels were helpful as an indicator of need for further studies to establish the diagnosis of systemic sarcoidosis. ACE levels in CSF were elevated in 20 of 24 patients. In the 20 patients who had both serum and CSF ACE levels, there was a poor correlation between the two levels (Spearman's r = 0.01, P = 0.96). This suggests that the CSF ACE levels may represent intrathecally synthesized ACE and not passive transfer from the serum. In the 24 patients that had CSF ACE and CSF protein available, there was a positive correlation between CSF ACE and CSF protein (Spearman's r = 0.625, P = 0.0011). This agrees with the suggestion that CSF protein and CSF ACE co-vary, as proposed by Zajicek.23 However, CSF ACE is a product of sarcoid granulomas, whereas increase in CSF protein is a nonspecific indicator of inflammation. Therefore increased CSF ACE may still have utility in the diagnosis of NS. In six of our patients there was normal CSF protein but elevated CSF ACE, pointing towards NS (Supplementary table). Therefore we would recommend measuring CSF ACE in cases of suspected NS.

There have been no controlled trials of treatment in neurosarcoidosis. Corticosteroids are accepted as the first line of treatment.24 In our series, most patients received an initial pulse of high dose corticosteroids, followed in many by maintenance immunosuppression. Based on our experience, there is comparable efficacy between long-term methotrexate, azathioprine and mycophenolate mofetil, and treatment decisions may be made on the basis of tolerability and adverse effects. A monoclonal antibody against TNF alpha, infliximab,25 and a combination of infliximab and mycophenolate mofetil26 have been recently used to treat NS resistant to steroids and nonspecific immunosuppression and represent new options in the treatment of refractory NS.

Conclusions

The diagnosis of neurosarcoidosis remains in the purview of clinical suspicion. Unlike systemic sarcoidosis, there is difficulty in making tissue diagnosis when involvement of CNS is suspected. MRI and CSF studies are sensitive in the detection of CNS inflammation but lack specificity, making the ascertainment of neurosarcoidosis a clinical challenge. In addition the low prevalence of the disease makes clinical trials difficult and therapeutic decisions are likely to be made from careful reporting from case studies.

Representative case histories

Case 1: Extensive neurosarcoidosis involving cerebral hemispheres, thalamus and brainstem (patient 4)

A 66-year-old woman presented with a 2-month history of bilateral ptosis. On examination she was only partly oriented to place and time, and was unable to do serial seven subtractions. She had bilateral ptosis, visual acuity of 20/200 either eye, a nonreactive pupil on the left and poorly reactive pupil on the right. She had diffuse weakness and was unable to stand without support, and had choreiform movements of arms. Brain MRI showed extensive T2 hyperintense lesions (Figure 1) in the cerebral hemispheres, thalamus, hypothalamus and brainstem. Her differential diagnosis included CNS vasculitis, neurosarcoidosis, Whipple's disease, other infectious causes, and paraneoplastic encephalitis, but workup for the latter three was negative. The extensive contrast enhancement from the roof of the fourth ventricle to the midbrain was suggestive of a brainstem glioma or CNS lymphoma, but biopsy of the lesion was consistent with sarcoidosis although lymphomatoid granulomatosis could not be ruled out by appearance. The absence of clonal B-cell populations and Epstein-Barr virus however made lymphomatoid granulomatosis less likely. A whole-body gallium scan showed extensive uptake in the mediastinum, consistent with a clinical picture of sarcoidosis. She was given prednisone and azathioprine with initial improvement, but continued to decline slowly over the next 18 months, when she lost to follow up.

Case 2: Seizures, enhancing widespread parenchymal nodules (patient 26)

A 27-year-old male with an unremarkable medical history had a generalized seizure and became acutely unresponsive. An MRI showed innumerable enhancing nodules throughout the subcortical white matter, cerebellum, and brainstem (Figure 2). CSF studies showed a protein of 410, glucose of 45, 53 WBC with 52% lymphocytes, and a CSF ACE of 4. Thoracic and abdominal CT scans showed extensive lymphadenopathy. He was also found to have bilateral testicular masses, and had a biopsy of one of these lesions. It was consistent with sarcoidosis. He was treated with high-dose prednisone and dilantin for his seizures. He was stable with no focal neurological deficits at 6 months and subsequently lost in follow up.

Case 3: Ataxia, posterior fossa leptomeningeal enhancement (patient 8)

A 48-year-old woman presented in 2001 with headaches that had begun 5–6 years prior, and more recent onset of balance problems. She was found to have weakness in her lower extremities, and truncal as well as limb ataxia. CSF showed a cell count of 21, glucose of 24 mg/dl, protein of 273 mg/dl, and the cultures were negative. MRI showed extensive meningeal enhancement in the posterior fossa (Figure 3). She underwent suboccipital craniotomy with open biopsy of dura, arachnoid and cerebellar tonsils, and the results were consistent with sarcoidosis. She was given IVMP, 1 g daily for 5 days, followed by prednisone and methotrexate. She showed no improvement after 4 months, and was given cyclophosphamide for two courses that she could not tolerate. She was therefore given mitoxantrone for one dose followed by etanercept for 12 weeks, and continued to worsen slowly through this time. She was then given prednisone and mycophenolate mofetil, which seemed to be better tolerated. She continued to improve slowly and a repeat MRI 2 years later showed resolution of the meningeal enhancement. Her lower extremity weakness did not improve and she remains wheel chair bound 6 years after meningeal biopsy.

Case 4: Optic neuropathy (patient 46)

A 46-year-old right-handed woman woke up with bilateral visual blurring. This persisted for approximately 1 week and resolved after steroids. Her symptoms returned after a month and this time she did not respond very well to the steroids, and she essentially lost vision in her left eye. She had an extensive evaluation including a spinal fluid exam that showed 11 cells and an elevated protein of 55. She also had a slightly elevated ESR of 25. Her SPEP was normal. A chest CT showed sequelae of granulomatous disease. An MRI of the brain showed bilateral enhancement of optic nerves, enlargement of the optic chiasm with marked enhancement (Figure 4), as well as leptomeningeal enhancement of the cerebellum. She was treated with corticosteroids and azathioprine. She continued to worsen slowly over the next few years and became legally blind in both eyes.

Case 5: Apparent Glioma (patient 2)

A then 32-year-old man had a generalized tonic-clonic seizure in November 2004. After an initial CT scan showed a left temporal lobe mass, he was referred to neurosurgery. A follow-up MRI showed a left temporal globular mass with edema and contrast-enhancement (Figure 5), concerning for a glioma although the appearance was thought to be atypical. He was scheduled for excision after a functional MRI showed that the speech areas were not involved. He received dexamethasone to reduce the edema prior to craniotomy, and the preoperative MRI showed significant resolution of the lesion and the surgery was changed to an open biopsy. The histology was consistent with sarcoidosis. He was continued on dilantin and steroids. He had another seizure in January 2006. A brain MRI showed resolution of mass effect and edema, but there was persistent enhancement. MMF and levetiracetam were added, and he has been seizure-free for the last 3 years.

Case 6: Sarcoid vasculitis (patient 9)

A then 38-year-old male began to have seizures in 2003. A brain MRI showed an occipital enhancing mass that was biopsied and was consistent with sarcoidosis. He was treated with steroids and phenytoin for seizures, and did well with occasional breakthrough seizures until early 2006, when he had a generalized tonic-clonic seizure and became unresponsive. A repeat brain MRI showed extensive infarcts in the brainstem and thalamus (Figure 7), presumably as a result of sarcoid vasculitis. He entered a persistent vegetative state from which he never recovered.

Case 7: Spinal cord sarcoidosis (patient 18)

A then 34-year-old woman presented in 2005 with lost feeling in both feet. This ascended up her legs and by the third day was to her hips. Her brain MRI was normal, and spinal cord MRI showed an enhancing lesion that extended from T2 to T7 (Figure 8). Her CSF showed an increased cell count of 57 and a high protein of 186 mg/dl. She also had pulmonary symptoms and used ambulatory oxygen for dyspnea. Her chest X-ray showed sequelae of granulomatous disease, and she had an elevated serum ACE of 96. She was given azathioprine and noted improvement in her symptoms. A subsequent MRI in 2007 showed a resolution of the lesion seen earlier.

Case 8: Multiple cranial neuropathy (patient 19)

A 32-year-old man noticed left-sided facial weakness. He was treated for Bell's palsy using steroids and acyclovir, and the weakness resolved in 4 weeks. Two weeks later he had numbness in the medial aspect of the left leg but did not seek medical attention. After a further 2 weeks, he started to experience double vision, and a recurrence of facial weakness. He also had headaches, global but predominantly in the left frontoparietal region, constant, throbbing, unresponsive to NSAIDs. The left frontoparietal area became numb. He saw an Ophthalmologist who started doxycycline for presumed Lyme disease. A brain MRI was normal. He had a serum ACE of 92. A CSF study showed an elevated protein of 76, and a lymphocytic pleocytosis (250 WBC, 75% lymphocytes). Chest X-ray and CT in the course of investigations showed enlarged hilar lymph nodes and he underwent biopsy. The pathology was consistent with sarcoidosis. He was started on steroids. His headaches disappeared soon after. After several months of high-dose steroids, his diplopia and facial weakness resolved. His steroids were tapered and he was started on mycophenolate mofetil. He has had a normal neurological examination for the last 24 months.

Supplementary data

Supplementary data are available at QJMED online.

Conflict of interest: None declared.

References

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