Acta Neurol Belg DOI 10.1007/s13760-015-0508-y
LETTER TO THE EDITOR
Neurosyphilis mimicking young-onset Alzheimer’s disease: a case report explaining the pitfalls of FDG-PET Sarah Verjans1 • Koen Van Laere2 • Rik Vandenberghe1
Received: 30 April 2015 / Accepted: 2 July 2015 Ó Belgian Neurological Society 2015
Introduction The use of FDG-PET in diagnosing Alzheimer’s dementia (AD) has recently increased. Precuneus and posterior cingulate are among the most sensitive regions in the early stages of AD. We present FDG-PET findings in a case of neurosyphilis presenting with rapidly progressive dementia. The case highlights a difficult differential diagnosis with young-onset Alzheimer’s on both clinical and neuroimaging grounds. The FDG pattern of diffuse temporoparietal hypometabolism and spared thalamic metabolism is a new finding in neurosyphilis.
Case report This 56-year-old heterosexual Caucasian man presented together with his wife to our outpatient clinic because of a 3-month history of progressive memory disturbances compromising his profession. He also complained of a vague feeling of ‘something going on in his head’ but denied true pain. Cardiovascular risk factors included smoking. Three months before, he was admitted to another hospital after a presyncopal episode. Given a history of myocardial infarction 10 years ago, he was evaluated at the cardiac department and discharged afterwards. He lost 7 kg since that event. Mini-mental state examination score was 22/30 (orientation in time 0/5; delayed recall 0/3). The 1-min animal & Sarah Verjans [email protected] 1
Department of Neurology, UZ Gasthuisberg, Leuven 3000, Belgium
2
Nuclear Department, UZ Gasthuisberg, Leuven 3000, Belgium
verbal fluency score was only 11. There was bradyphrenia and apathy. Clinical neurological evaluation was normal apart from reduced Achilles tendon reflexes (1/4) and a mildly broad-based gait. There were no Argyll Robertson pupils. General physical examination was normal. Three-tesla MRI revealed moderate hippocampal atrophy Scheltens scale two as well as global volume loss (Fig. 1). No white matter changes and no gadolinium enhancement were seen. Neuropsychological evaluation confirmed problems in episodic memory, executive functions, word generation, naming and constructional praxis. There was also a moderate depressive state. Routine biochemistry revealed a sedimentation rate of 56 mm/h, with normal CRP and autoimmune screening. Thyroid function and vitamin status were also normal. Brain FDG-PET showed severe hypometabolism in the inferior temporal gyrus, spreading anteriorly (anterior temporal and orbitofrontal areas) and into precuneus and intraparietal sulcus (Fig. 2). Given the medial parietal hypometabolism, the nuclear medicine protocol concluded that the findings were compatible with Alzheimer’s disease. On follow-up visit after 3 months, cognitive decline was remarkable. Paraneoplastic serum antibodies were negative. The VDRL test was positive with an RPR titer of 1:64, HIV serology test was negative. His wife then recalled an untreated penile rash 12 years ago. A lumbar puncture confirmed the diagnosis of neurosyphilis (total cell count of 80/ll of which 96 % lymphocytes, normal glucose, protein 1094 g/l, VDRL 1:8, Direct Treponemal Antibody testing positive). ELISA for AD biomarkers (Fujirebio, Belgium) revealed a CSF total tau above 1200 pg/ml (normal value \367 pg/ml), phospho-tau181 of 44.3 pg/ml (normal value \80 pg/ml), and Ab1–42 of 690 pg/ml (normal value [500 pg/ml). The
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Acta Neurol Belg
Fig. 1 Brain MRI showing mild global and hippocampal atrophy but no white matter changes or gadolinium enhancement
Ab1–42 and phospho-tau181 levels are outside the range that is typically seen in Alzheimer’s disease. Three weeks of IV penicillin were administered without clinical improvement. During the hospitalisation, he had an episode suggestive of angor. Cardiac evaluation showed an aortitis, probably due to tertiary syphilis. He developed a severe psycho-organic syndrome necessitating permanent institutionalisation.
Discussion Although neurosyphilis can cause young-onset dementia, it can be very difficult to recognise if a priori probability is low. In our case, not only the clinical findings, but also the
123
pattern seen on imaging could be confused with rapidly progressive Alzheimer’s. Brain MRI shows different patterns in tertiary neurosyphilis ranging from global atrophy to extensive white matter lesions or even normal findings [1, 2]. Recently, limbic and even frontal encephalitis were also described [3]. Even fewer data exist on the appearance on FDG-PET, a technique commonly used in dementia clinics for differentiation between frontotemporal lobar degeneration (FTLD) and Alzheimer’s, in particular in early-onset dementia. There are no reviews in the English literature on this matter. A small Austrian study [4] reported global reduction in glucose consumption in particular in the frontal areas with sparing of basal ganglia and thalamus in neurosyphilis. Other reports mention a variety of FDG-PET patterns ranging from hypermetabolic temporal lobes to focal temporal hypometabolism [5]. In our case, FDG-PET revealed severe hypometabolism of inferior temporal cortex and precuneus/posterior cingulate (Fig. 2). Involvement of the anterior inferior temporal gyrus, anterior temporal pole and orbitofrontal cortex is atypical for AD. The hypometabolism in precuneus and posterior cingulate was considered to be suggestive of AD. Our case clearly illustrates this sign is not specific for AD. We postulate that its status as a hub within the default mode network makes it vulnerable to hypometabolism in various types of multifocal extensive brain disease. According to EFNS guidelines [6], serologic testing for syphilis is only considered in individual cases at high risk or when suggestive clinical findings are present, but lumbar puncture is recommended in young-onset or rapidly progressive dementia. This case illustrates the diagnostic importance of serologic testing and lumbar puncture in these situations. Furthermore, it shows the value of more specific biomarkers of cerebral amyloidosis, such as CSF parameters or amyloid PET to eliminate AD.
Acta Neurol Belg
Fig. 2 FDG-PET. Most prominent hypometabolism (in green) is seen in the inferior temporal gyrus, anterior temporal lobe, orbitofrontal lobe and the posterior gyrus cingulum/precuneus (partly) as well as the intraparietal sulcus. The lateral occipital cortex shows also some
reduced tracer uptake. Z-map (below) shows the hypometabolism is most pronounced in the posterior gyrus cingulum/precuneus compared with age-matched controls
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Acta Neurol Belg Conflict of interest to disclose.
None of the authors has any conflict of interest 3.
Ethical standard We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Anonymity of the patient was protected at all times.
4.
5.
References 1. Peng F, Hu X, Zhong X, Wei Q, Jiang Y, Bao J, Wu A, Pei Z (2008) CT and MR findings in HIV-negative neurosyphilis. Eur J Radiol 66(1):1–6 2. Yu Y, Wei M, Huang Y, Jiang W, Liu X, Xia F, Li D, Zhao G (2010) Clinical presentation and imaging of general paresis due to
123
6.
neurosyphilis in patients negative for human immunodeficiency virus. J Clin Neurosci 17(3):308–310 Aizawa H, Yomono H, Kurisaki H (2013) Neurosyphilis presenting as frontal and mesial temporal encephalitis. Intern Med 52(20):2381–2382 Pichler R, Doppler S, Szalay E, Hertl C, Knell U, Winkler J (2008) SPECT and FDG-PET in diagnostics of neurolues. Wien Klin Wochenschr 120:20–23 Scheid R, Voltz R, Vetter T, Sabri O, von Cramon DY (2005) Neurosyphilis and paraneoplastic limbic encephalitis: important differential diagnoses. J Neurol 252:1129–1132 Hort J, O’Brien JT, Gainotti G et al (2010) EFNS guidelines for the diagnosis and management of Alzheimer’s disease. Eur J Neurol 17(10):1236–1248
LETTER TO THE EDITOR
Neurosyphilis mimicking young-onset Alzheimer’s disease: a case report explaining the pitfalls of FDG-PET Sarah Verjans1 • Koen Van Laere2 • Rik Vandenberghe1
Received: 30 April 2015 / Accepted: 2 July 2015 Ó Belgian Neurological Society 2015
Introduction The use of FDG-PET in diagnosing Alzheimer’s dementia (AD) has recently increased. Precuneus and posterior cingulate are among the most sensitive regions in the early stages of AD. We present FDG-PET findings in a case of neurosyphilis presenting with rapidly progressive dementia. The case highlights a difficult differential diagnosis with young-onset Alzheimer’s on both clinical and neuroimaging grounds. The FDG pattern of diffuse temporoparietal hypometabolism and spared thalamic metabolism is a new finding in neurosyphilis.
Case report This 56-year-old heterosexual Caucasian man presented together with his wife to our outpatient clinic because of a 3-month history of progressive memory disturbances compromising his profession. He also complained of a vague feeling of ‘something going on in his head’ but denied true pain. Cardiovascular risk factors included smoking. Three months before, he was admitted to another hospital after a presyncopal episode. Given a history of myocardial infarction 10 years ago, he was evaluated at the cardiac department and discharged afterwards. He lost 7 kg since that event. Mini-mental state examination score was 22/30 (orientation in time 0/5; delayed recall 0/3). The 1-min animal & Sarah Verjans [email protected] 1
Department of Neurology, UZ Gasthuisberg, Leuven 3000, Belgium
2
Nuclear Department, UZ Gasthuisberg, Leuven 3000, Belgium
verbal fluency score was only 11. There was bradyphrenia and apathy. Clinical neurological evaluation was normal apart from reduced Achilles tendon reflexes (1/4) and a mildly broad-based gait. There were no Argyll Robertson pupils. General physical examination was normal. Three-tesla MRI revealed moderate hippocampal atrophy Scheltens scale two as well as global volume loss (Fig. 1). No white matter changes and no gadolinium enhancement were seen. Neuropsychological evaluation confirmed problems in episodic memory, executive functions, word generation, naming and constructional praxis. There was also a moderate depressive state. Routine biochemistry revealed a sedimentation rate of 56 mm/h, with normal CRP and autoimmune screening. Thyroid function and vitamin status were also normal. Brain FDG-PET showed severe hypometabolism in the inferior temporal gyrus, spreading anteriorly (anterior temporal and orbitofrontal areas) and into precuneus and intraparietal sulcus (Fig. 2). Given the medial parietal hypometabolism, the nuclear medicine protocol concluded that the findings were compatible with Alzheimer’s disease. On follow-up visit after 3 months, cognitive decline was remarkable. Paraneoplastic serum antibodies were negative. The VDRL test was positive with an RPR titer of 1:64, HIV serology test was negative. His wife then recalled an untreated penile rash 12 years ago. A lumbar puncture confirmed the diagnosis of neurosyphilis (total cell count of 80/ll of which 96 % lymphocytes, normal glucose, protein 1094 g/l, VDRL 1:8, Direct Treponemal Antibody testing positive). ELISA for AD biomarkers (Fujirebio, Belgium) revealed a CSF total tau above 1200 pg/ml (normal value \367 pg/ml), phospho-tau181 of 44.3 pg/ml (normal value \80 pg/ml), and Ab1–42 of 690 pg/ml (normal value [500 pg/ml). The
123
Acta Neurol Belg
Fig. 1 Brain MRI showing mild global and hippocampal atrophy but no white matter changes or gadolinium enhancement
Ab1–42 and phospho-tau181 levels are outside the range that is typically seen in Alzheimer’s disease. Three weeks of IV penicillin were administered without clinical improvement. During the hospitalisation, he had an episode suggestive of angor. Cardiac evaluation showed an aortitis, probably due to tertiary syphilis. He developed a severe psycho-organic syndrome necessitating permanent institutionalisation.
Discussion Although neurosyphilis can cause young-onset dementia, it can be very difficult to recognise if a priori probability is low. In our case, not only the clinical findings, but also the
123
pattern seen on imaging could be confused with rapidly progressive Alzheimer’s. Brain MRI shows different patterns in tertiary neurosyphilis ranging from global atrophy to extensive white matter lesions or even normal findings [1, 2]. Recently, limbic and even frontal encephalitis were also described [3]. Even fewer data exist on the appearance on FDG-PET, a technique commonly used in dementia clinics for differentiation between frontotemporal lobar degeneration (FTLD) and Alzheimer’s, in particular in early-onset dementia. There are no reviews in the English literature on this matter. A small Austrian study [4] reported global reduction in glucose consumption in particular in the frontal areas with sparing of basal ganglia and thalamus in neurosyphilis. Other reports mention a variety of FDG-PET patterns ranging from hypermetabolic temporal lobes to focal temporal hypometabolism [5]. In our case, FDG-PET revealed severe hypometabolism of inferior temporal cortex and precuneus/posterior cingulate (Fig. 2). Involvement of the anterior inferior temporal gyrus, anterior temporal pole and orbitofrontal cortex is atypical for AD. The hypometabolism in precuneus and posterior cingulate was considered to be suggestive of AD. Our case clearly illustrates this sign is not specific for AD. We postulate that its status as a hub within the default mode network makes it vulnerable to hypometabolism in various types of multifocal extensive brain disease. According to EFNS guidelines [6], serologic testing for syphilis is only considered in individual cases at high risk or when suggestive clinical findings are present, but lumbar puncture is recommended in young-onset or rapidly progressive dementia. This case illustrates the diagnostic importance of serologic testing and lumbar puncture in these situations. Furthermore, it shows the value of more specific biomarkers of cerebral amyloidosis, such as CSF parameters or amyloid PET to eliminate AD.
Acta Neurol Belg
Fig. 2 FDG-PET. Most prominent hypometabolism (in green) is seen in the inferior temporal gyrus, anterior temporal lobe, orbitofrontal lobe and the posterior gyrus cingulum/precuneus (partly) as well as the intraparietal sulcus. The lateral occipital cortex shows also some
reduced tracer uptake. Z-map (below) shows the hypometabolism is most pronounced in the posterior gyrus cingulum/precuneus compared with age-matched controls
123
Acta Neurol Belg Conflict of interest to disclose.
None of the authors has any conflict of interest 3.
Ethical standard We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Anonymity of the patient was protected at all times.
4.
5.
References 1. Peng F, Hu X, Zhong X, Wei Q, Jiang Y, Bao J, Wu A, Pei Z (2008) CT and MR findings in HIV-negative neurosyphilis. Eur J Radiol 66(1):1–6 2. Yu Y, Wei M, Huang Y, Jiang W, Liu X, Xia F, Li D, Zhao G (2010) Clinical presentation and imaging of general paresis due to
123
6.
neurosyphilis in patients negative for human immunodeficiency virus. J Clin Neurosci 17(3):308–310 Aizawa H, Yomono H, Kurisaki H (2013) Neurosyphilis presenting as frontal and mesial temporal encephalitis. Intern Med 52(20):2381–2382 Pichler R, Doppler S, Szalay E, Hertl C, Knell U, Winkler J (2008) SPECT and FDG-PET in diagnostics of neurolues. Wien Klin Wochenschr 120:20–23 Scheid R, Voltz R, Vetter T, Sabri O, von Cramon DY (2005) Neurosyphilis and paraneoplastic limbic encephalitis: important differential diagnoses. J Neurol 252:1129–1132 Hort J, O’Brien JT, Gainotti G et al (2010) EFNS guidelines for the diagnosis and management of Alzheimer’s disease. Eur J Neurol 17(10):1236–1248
