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CT scanning in the diagnosis of neurosarcoidosis
Case Reports / Journal of Clinical Neuroscience 19 (2012) 1461–1462
abnormalities is often slow.5,9 Approximately 50% of patients have disease recurrence, most of whom may require continuous treatment with immunomodulatory treatment to maintain remission.3 Other important differentials include limbic encephalitis, viral encephalitis, prion diseases, metabolic encephalopathies, degenerative dementias and encephalopathies related to other autoimmune disease. In conclusion, the clinicoradiologic findings associated with SREAT are varied and a high index of suspicion is necessary. Until the pathophysiologic mechanism of this and other autoimmune encephalopathies are better characterised, we believe that descriptive terms that reflect an association, rather than causation, are more appropriate for this syndrome. References 1. Stevens RB, Wakefield CB, Alonso D, et al. Hashimoto’s encephalopathy after intensive lymphocyte depletion with rabbit anti-thymocyte globulin in a renal transplant patient. Am J Transplant 2008;8:245–9.
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2. Brain L, Jellinek EH, Ball K. Hashimoto’s disease and encephalopathy. Lancet 1966;2:512–4. 3. Castillo P, Woodruff B, Caselli R, et al. Steroid-responsive encephalopathy associated with autoimmune thyroiditis. Arch Neurol 2006;63:197–202. 4. Schauble B, Castillo PR, Boeve BF, et al. EEG findings in steroid-responsive encephalopathy associated with autoimmune thyroiditis. Clin Neurophysiol 2003;114:32–7. 5. Henchey R, Cibula J, Helveston W, et al. Electroencephalographic findings in Hashimoto’s encephalopathy. Neurology 1995;45:977–81. 6. Giovanella L, Pedrazzi P, Jandus P, et al. Steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) with negative thyroperoxidase antibodies. Eur J Clin Invest 2008;38:693–4. 7. Fauci AS. Harrison’s principles of internal medicine. 17th ed. New York: McGrawHill Medical; 2008. 8. Blanchin S, Coffin C, Viader F, et al. Anti-thyroperoxidase antibodies from patients with Hashimoto’s encephalopathy bind to cerebellar astrocytes. J Neuroimmunol 2007;192:13–20. 9. Rodriguez AJ, Jicha GA, Steeves TD, et al. EEG changes in a patient with steroidresponsive encephalopathy associated with antibodies to thyroperoxidase (SREAT, Hashimoto’s encephalopathy). J Clin Neurophysiol 2006;23:371–3. 10. Caselli RJ, Boeve BF, Scheithauer BW, et al. Nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM): a reversible form of encephalopathy. Neurology 1999;53:1579–81.
doi:http://dx.doi.org10.1016/j.jocn.2011.10.023
The value of [18F]-fluorodeoxyglucose–positron emission tomography/CT scanning in the diagnosis of neurosarcoidosis M. Meenakshi a,b, Colin Arnold b, Simon A Broadley a,b,⇑ a b
School of Medicine, Gold Coast Campus, Griffith University, Queensland, Australia Department of Neurology, Gold Coast Hospital, Southport, Queensland 4215, Australia
a r t i c l e
i n f o
Article history: Received 17 February 2012 Accepted 26 February 2012
Keywords: Granuloma Lymphocytic meningitis Neurosarcoidosis PET scan
a b s t r a c t Sarcoidosis is a granulomatous disease of unknown aetiology which primarily affects the lungs, but can affect other tissues including the central nervous system (CNS). In neurosarcoidodis, the CNS is often the only affected site, which makes a tissue diagnosis difficult. Although a clinical diagnosis of neurosarcoidosis can often be made, the wide range of potential differential diagnoses, including other steroid responsive conditions (such as idiopathic lymphocytic meningitis) means that a confirmed diagnosis is invaluable. This is particularly important because neurosarcoidosis has a poor prognosis and aggressive immunosuppressive treatment is generally recommended. We present a man with clinically suspected neurosarcoidosis where attempts to obtain histological confirmation of the disease through skin and meningeal biopsy was unhelpful, but a lymph node biopsy, directed with the use of [18F]-fluorodeoxyglucose–positron emission tomography/CT scanning was diagnostic. Crown Copyright Ó 2012 Published by Elsevier Ltd. All rights reserved.
1. Introduction Sarcoidosis is a granulomatous disease of unknown aetiology which primarily affects the lungs but can affect other tissues, including the central nervous system.1 In neurosarcoidosis the central nervous system (CNS) is often the only affected site making a tissue diagnosis difficult.1 Whilst a clinical diagnosis of neurosarcoidosis can often be made,2 the wide range of potential differential diagnoses, including other steroid responsive conditions (such as idiopathic lymphocytic meningitis) means a confirmed diagnosis is invaluable. This is particularly important because neurosarcoidosis has a poor prognosis and aggressive immunosuppressive treatment is generally recommended.1 ⇑ Corresponding author. Tel.: +61 7 5678 0702; fax: +44 7 5678 0708. E-mail address: simon.broadley@griffith.edu.au (S.A Broadley).
We present a man with clinically suspected neurosarcoidosis where attempts to obtain histological confirmation of disease through skin and meningeal biopsy was unhelpful but lymph node biopsy, directed with the use of [18F]-fluorodeoxyglucose (FDG)– positron emission tomography/CT (FDG–PET/CT) scanning, was diagnostic. 2. Case report A 27-year-old male presented with a 4 week history of intractable occipital and frontal headache with vomiting, fever, arthralgia and rash. Admission was precipitated by acute onset of right-sided incoordination and slurred speech. There was a history of 20 kg weight gain over the preceding 6 months. There was no past history of note. Alcohol consumption was 42 units of alcohol per week, and he was a non-smoker.
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Case Reports / Journal of Clinical Neuroscience 19 (2012) 1461–1462
phragm. The most intense uptake was seen within mildly enlarged inguinal/femoral lymph nodes bilaterally (Fig. 1C). There was no evidence of FDG uptake within the CNS. Core biopsies of the inguinal lymph nodes, bilaterally, were performed and histology showed granulomatous lymphadenopathy (Fig. 1D). The granulomas were of non-caseating sarcoidal-type composed of epithelioid histiocytes with occasional multinucleated giant cells. The ZiehlNeelsen stain for acid-fast bacilli and periodic acid-Schiff and Grocott’s stains for fungi were negative. The patient was continued on a gradually tapering dose of oral prednisolone and commenced on oral cyclophosphamide after collection and freezing of semen. Oral bisphosphonates, proton pump inhibitor and prophylactic high dose sulfamethoxazole and trimethoprim were also commenced. At 12 months of follow-up there had been no further neurological episodes and no recurrence of headache. Repeat CSF analysis revealed a normal white cell count and protein concentration of 0.75 g/L. 3. Discussion
Fig. 1. (A) A photograph of the right knee (anterior) showing multiple small (red) nodules, (B) axial diffusion-weighted MRI at the mid-pons showing high signal in the anterior left pons (arrow), (C) coronal [18F]-fluorodeoxyglucose (FDG)–positron emission tomography/CT scan showing enlargement and increased FDG uptake in the inguinal lymph nodes bilaterally (arrows), and (D) high resolution micrograph of the core biopsy of the inguinal lymph node showing non-caseating sarcoidal-type granuloma (arrow). This figure is available in colour at www.sciencedirect.com.
On examination, there were signs of cerebellar dysarthria, rightsided limb ataxia and gait ataxia. There was a low grade fever (38.0 °C) on admission, and his weight was 120 kg. There was no neck stiffness, photophobia or papilloedema. There were tender, firm, red nodules measuring 10–15 mm in diameter confined to the medial aspects of the forearms and anterior of the legs and knees, consistent with erythema nodosum (Fig. 1A). Respiratory examination was normal and there were no palpable lymph nodes. Inflammatory markers were moderately elevated (erythrocyte sedimentation rate, 78 mm/hour and C-reactive protein, 121 mg/ L). Lumbar puncture showed an opening pressure of 33 cm of water, cerebrospinal fluid (CSF) analysis showed a white cell count of 224 (100% lymphocytes), glucose 3.0 mmol/L (plasma, 6.8 mmol/L) and protein 0.90 g/L. MRI brain confirmed left pontine infarction (Fig. 1B) and subtle T2-weighted hyperintensity in the region of the hypothalamus. A clinical diagnosis of neurosarcoidosis was made and treatment with intravenous methylprednisolone was commenced. The headache, fever and rash settled promptly, and the right hemiataxia and dysarthria slowly improved. Investigations, including chest radiography, CT scans of the chest, abdomen and pelvis, CSF culture for tuberculosis, thrombophilic, vasculitic and autoimmune screens, the polymerase chain reaction of the CSF and enzyme-linked immunosorbent assays for cryptococcal antigen, enterovirus, herpes simplex virus, cytomegalovirus and Epstein-Barr virus were all negative. CSF angiotensin-converting enzyme (ACE) level was 6 U/L (reference, <5 U/L) and the serum ACE level was 46 U/L (reference 20–130 U/L). The quantiferon gold test was indeterminate. A punch biopsy of the lower limb skin rash was non-diagnostic. Posterior fossa meningeal biopsy showed slightly thickened meninges with no specific pathological features. FDG–PET/CT scanning revealed variable intensity of FDG uptake within multiple nodal groups, both above and below the diadoi:http://dx.doi.org10.1016/j.jocn.2012.02.013
The diagnosis of neurosarcoidosis is challenging, given the frequent absence of other organ involvement and the potential for sampling error on biopsy of the meninges and parenchyma, even when lesions are evident on MRI.3 Since the fall from favour of the Kviem test, due to concerns about blood-borne infection and prion disease,4 definitive diagnosis of neurosarcoidosis can be established only through histological evidence of granulomas and exclusion of other possible causes. The recommended treatment includes steroids and immunosuppression, with alpha-interferon as second line treatment. In view of the potential for disease recurrence and significant side effects with such therapy, a definitive diagnosis is highly desirable. This patient had a clinical presentation which was highly suspicious of neurosarcoidosis but initially had no supporting radiological, serological or histological investigations, including a negative meningeal biopsy. Extensive investigations to exclude other potential causes was helpful, but the possibility of idiopathic lymphocytic meningitis could not be excluded, a condition which normally responds to steroids alone.5 FDG–PET/CT scan revealed the disease process in multiple lymph nodes and guided the biopsy to obtain a histological diagnosis. FDG-PET/CT scanning can be used to evaluate the extent of disease and to target an optimal site for biopsy in pulmonary sarcoidosis.6 This report highlights the value of this investigation in neurosarcoidosis. Thus, early investigation with FDG–PET/CT scanning should be considered in patients with suspected neurosarcoidosis. References 1. Zajicek JP, Scolding NJ, Foster O, et al. Central nervous system sarcoidosis– diagnosis and management. Q J Med 1999;92:103–17. 2. Pawate S, Moses H, Sriram S. Presentations and outcomes of neurosarcoidosis: a study of 54 cases. Q J Med 2009;102:449–60. 3. Kim SK, Im HJ, Kim W, et al. F-18 fluorodeoxyglucose and F-18 fluorothymidine positron emission tomography/computed tomography imaging in a case of neurosarcoidosis. Clin Nucl Med 2010;35:67–70. 4. Judson MA. The diagnosis of sarcoidosis. Clin Chest Med 2008;29:415–27, viii. 5. Charleston AJ, Anderson NE, Willoughby EW. Idiopathic steroid responsive chronic lymphocytic meningitis–clinical features and long-term outcome in 17 patients. Aust N Z J Med 1998;28:784–9. 6. Aide N, Benayoun M, Kerrou K, et al. Impact of [18F]-fluorodeoxyglucose ([18F]FDG) imaging in sarcoidosis: unsuspected neurosarcoidosis discovered by [18F]FDG PET and early metabolic response to corticosteroid therapy. Br J Radiol 2007;80:e67–71.
abnormalities is often slow.5,9 Approximately 50% of patients have disease recurrence, most of whom may require continuous treatment with immunomodulatory treatment to maintain remission.3 Other important differentials include limbic encephalitis, viral encephalitis, prion diseases, metabolic encephalopathies, degenerative dementias and encephalopathies related to other autoimmune disease. In conclusion, the clinicoradiologic findings associated with SREAT are varied and a high index of suspicion is necessary. Until the pathophysiologic mechanism of this and other autoimmune encephalopathies are better characterised, we believe that descriptive terms that reflect an association, rather than causation, are more appropriate for this syndrome. References 1. Stevens RB, Wakefield CB, Alonso D, et al. Hashimoto’s encephalopathy after intensive lymphocyte depletion with rabbit anti-thymocyte globulin in a renal transplant patient. Am J Transplant 2008;8:245–9.
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2. Brain L, Jellinek EH, Ball K. Hashimoto’s disease and encephalopathy. Lancet 1966;2:512–4. 3. Castillo P, Woodruff B, Caselli R, et al. Steroid-responsive encephalopathy associated with autoimmune thyroiditis. Arch Neurol 2006;63:197–202. 4. Schauble B, Castillo PR, Boeve BF, et al. EEG findings in steroid-responsive encephalopathy associated with autoimmune thyroiditis. Clin Neurophysiol 2003;114:32–7. 5. Henchey R, Cibula J, Helveston W, et al. Electroencephalographic findings in Hashimoto’s encephalopathy. Neurology 1995;45:977–81. 6. Giovanella L, Pedrazzi P, Jandus P, et al. Steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) with negative thyroperoxidase antibodies. Eur J Clin Invest 2008;38:693–4. 7. Fauci AS. Harrison’s principles of internal medicine. 17th ed. New York: McGrawHill Medical; 2008. 8. Blanchin S, Coffin C, Viader F, et al. Anti-thyroperoxidase antibodies from patients with Hashimoto’s encephalopathy bind to cerebellar astrocytes. J Neuroimmunol 2007;192:13–20. 9. Rodriguez AJ, Jicha GA, Steeves TD, et al. EEG changes in a patient with steroidresponsive encephalopathy associated with antibodies to thyroperoxidase (SREAT, Hashimoto’s encephalopathy). J Clin Neurophysiol 2006;23:371–3. 10. Caselli RJ, Boeve BF, Scheithauer BW, et al. Nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM): a reversible form of encephalopathy. Neurology 1999;53:1579–81.
doi:http://dx.doi.org10.1016/j.jocn.2011.10.023
The value of [18F]-fluorodeoxyglucose–positron emission tomography/CT scanning in the diagnosis of neurosarcoidosis M. Meenakshi a,b, Colin Arnold b, Simon A Broadley a,b,⇑ a b
School of Medicine, Gold Coast Campus, Griffith University, Queensland, Australia Department of Neurology, Gold Coast Hospital, Southport, Queensland 4215, Australia
a r t i c l e
i n f o
Article history: Received 17 February 2012 Accepted 26 February 2012
Keywords: Granuloma Lymphocytic meningitis Neurosarcoidosis PET scan
a b s t r a c t Sarcoidosis is a granulomatous disease of unknown aetiology which primarily affects the lungs, but can affect other tissues including the central nervous system (CNS). In neurosarcoidodis, the CNS is often the only affected site, which makes a tissue diagnosis difficult. Although a clinical diagnosis of neurosarcoidosis can often be made, the wide range of potential differential diagnoses, including other steroid responsive conditions (such as idiopathic lymphocytic meningitis) means that a confirmed diagnosis is invaluable. This is particularly important because neurosarcoidosis has a poor prognosis and aggressive immunosuppressive treatment is generally recommended. We present a man with clinically suspected neurosarcoidosis where attempts to obtain histological confirmation of the disease through skin and meningeal biopsy was unhelpful, but a lymph node biopsy, directed with the use of [18F]-fluorodeoxyglucose–positron emission tomography/CT scanning was diagnostic. Crown Copyright Ó 2012 Published by Elsevier Ltd. All rights reserved.
1. Introduction Sarcoidosis is a granulomatous disease of unknown aetiology which primarily affects the lungs but can affect other tissues, including the central nervous system.1 In neurosarcoidosis the central nervous system (CNS) is often the only affected site making a tissue diagnosis difficult.1 Whilst a clinical diagnosis of neurosarcoidosis can often be made,2 the wide range of potential differential diagnoses, including other steroid responsive conditions (such as idiopathic lymphocytic meningitis) means a confirmed diagnosis is invaluable. This is particularly important because neurosarcoidosis has a poor prognosis and aggressive immunosuppressive treatment is generally recommended.1 ⇑ Corresponding author. Tel.: +61 7 5678 0702; fax: +44 7 5678 0708. E-mail address: simon.broadley@griffith.edu.au (S.A Broadley).
We present a man with clinically suspected neurosarcoidosis where attempts to obtain histological confirmation of disease through skin and meningeal biopsy was unhelpful but lymph node biopsy, directed with the use of [18F]-fluorodeoxyglucose (FDG)– positron emission tomography/CT (FDG–PET/CT) scanning, was diagnostic. 2. Case report A 27-year-old male presented with a 4 week history of intractable occipital and frontal headache with vomiting, fever, arthralgia and rash. Admission was precipitated by acute onset of right-sided incoordination and slurred speech. There was a history of 20 kg weight gain over the preceding 6 months. There was no past history of note. Alcohol consumption was 42 units of alcohol per week, and he was a non-smoker.
1462
Case Reports / Journal of Clinical Neuroscience 19 (2012) 1461–1462
phragm. The most intense uptake was seen within mildly enlarged inguinal/femoral lymph nodes bilaterally (Fig. 1C). There was no evidence of FDG uptake within the CNS. Core biopsies of the inguinal lymph nodes, bilaterally, were performed and histology showed granulomatous lymphadenopathy (Fig. 1D). The granulomas were of non-caseating sarcoidal-type composed of epithelioid histiocytes with occasional multinucleated giant cells. The ZiehlNeelsen stain for acid-fast bacilli and periodic acid-Schiff and Grocott’s stains for fungi were negative. The patient was continued on a gradually tapering dose of oral prednisolone and commenced on oral cyclophosphamide after collection and freezing of semen. Oral bisphosphonates, proton pump inhibitor and prophylactic high dose sulfamethoxazole and trimethoprim were also commenced. At 12 months of follow-up there had been no further neurological episodes and no recurrence of headache. Repeat CSF analysis revealed a normal white cell count and protein concentration of 0.75 g/L. 3. Discussion
Fig. 1. (A) A photograph of the right knee (anterior) showing multiple small (red) nodules, (B) axial diffusion-weighted MRI at the mid-pons showing high signal in the anterior left pons (arrow), (C) coronal [18F]-fluorodeoxyglucose (FDG)–positron emission tomography/CT scan showing enlargement and increased FDG uptake in the inguinal lymph nodes bilaterally (arrows), and (D) high resolution micrograph of the core biopsy of the inguinal lymph node showing non-caseating sarcoidal-type granuloma (arrow). This figure is available in colour at www.sciencedirect.com.
On examination, there were signs of cerebellar dysarthria, rightsided limb ataxia and gait ataxia. There was a low grade fever (38.0 °C) on admission, and his weight was 120 kg. There was no neck stiffness, photophobia or papilloedema. There were tender, firm, red nodules measuring 10–15 mm in diameter confined to the medial aspects of the forearms and anterior of the legs and knees, consistent with erythema nodosum (Fig. 1A). Respiratory examination was normal and there were no palpable lymph nodes. Inflammatory markers were moderately elevated (erythrocyte sedimentation rate, 78 mm/hour and C-reactive protein, 121 mg/ L). Lumbar puncture showed an opening pressure of 33 cm of water, cerebrospinal fluid (CSF) analysis showed a white cell count of 224 (100% lymphocytes), glucose 3.0 mmol/L (plasma, 6.8 mmol/L) and protein 0.90 g/L. MRI brain confirmed left pontine infarction (Fig. 1B) and subtle T2-weighted hyperintensity in the region of the hypothalamus. A clinical diagnosis of neurosarcoidosis was made and treatment with intravenous methylprednisolone was commenced. The headache, fever and rash settled promptly, and the right hemiataxia and dysarthria slowly improved. Investigations, including chest radiography, CT scans of the chest, abdomen and pelvis, CSF culture for tuberculosis, thrombophilic, vasculitic and autoimmune screens, the polymerase chain reaction of the CSF and enzyme-linked immunosorbent assays for cryptococcal antigen, enterovirus, herpes simplex virus, cytomegalovirus and Epstein-Barr virus were all negative. CSF angiotensin-converting enzyme (ACE) level was 6 U/L (reference, <5 U/L) and the serum ACE level was 46 U/L (reference 20–130 U/L). The quantiferon gold test was indeterminate. A punch biopsy of the lower limb skin rash was non-diagnostic. Posterior fossa meningeal biopsy showed slightly thickened meninges with no specific pathological features. FDG–PET/CT scanning revealed variable intensity of FDG uptake within multiple nodal groups, both above and below the diadoi:http://dx.doi.org10.1016/j.jocn.2012.02.013
The diagnosis of neurosarcoidosis is challenging, given the frequent absence of other organ involvement and the potential for sampling error on biopsy of the meninges and parenchyma, even when lesions are evident on MRI.3 Since the fall from favour of the Kviem test, due to concerns about blood-borne infection and prion disease,4 definitive diagnosis of neurosarcoidosis can be established only through histological evidence of granulomas and exclusion of other possible causes. The recommended treatment includes steroids and immunosuppression, with alpha-interferon as second line treatment. In view of the potential for disease recurrence and significant side effects with such therapy, a definitive diagnosis is highly desirable. This patient had a clinical presentation which was highly suspicious of neurosarcoidosis but initially had no supporting radiological, serological or histological investigations, including a negative meningeal biopsy. Extensive investigations to exclude other potential causes was helpful, but the possibility of idiopathic lymphocytic meningitis could not be excluded, a condition which normally responds to steroids alone.5 FDG–PET/CT scan revealed the disease process in multiple lymph nodes and guided the biopsy to obtain a histological diagnosis. FDG-PET/CT scanning can be used to evaluate the extent of disease and to target an optimal site for biopsy in pulmonary sarcoidosis.6 This report highlights the value of this investigation in neurosarcoidosis. Thus, early investigation with FDG–PET/CT scanning should be considered in patients with suspected neurosarcoidosis. References 1. Zajicek JP, Scolding NJ, Foster O, et al. Central nervous system sarcoidosis– diagnosis and management. Q J Med 1999;92:103–17. 2. Pawate S, Moses H, Sriram S. Presentations and outcomes of neurosarcoidosis: a study of 54 cases. Q J Med 2009;102:449–60. 3. Kim SK, Im HJ, Kim W, et al. F-18 fluorodeoxyglucose and F-18 fluorothymidine positron emission tomography/computed tomography imaging in a case of neurosarcoidosis. Clin Nucl Med 2010;35:67–70. 4. Judson MA. The diagnosis of sarcoidosis. Clin Chest Med 2008;29:415–27, viii. 5. Charleston AJ, Anderson NE, Willoughby EW. Idiopathic steroid responsive chronic lymphocytic meningitis–clinical features and long-term outcome in 17 patients. Aust N Z J Med 1998;28:784–9. 6. Aide N, Benayoun M, Kerrou K, et al. Impact of [18F]-fluorodeoxyglucose ([18F]FDG) imaging in sarcoidosis: unsuspected neurosarcoidosis discovered by [18F]FDG PET and early metabolic response to corticosteroid therapy. Br J Radiol 2007;80:e67–71.