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a Patient 1 MRI. T2-weighted image showing mild cortical atrophy more marked in both mesial temporal lobes. b Patient 1 SPECT showing diffuse cortical reduction of perfusion in frontal regions and in left parietotemporal cortex. c Patient 2 MRI. T2- weighted image, negative. d Patient 2 SPECT showing hypoperfusion of cerebral grey matter at both middle frontal regions and, to a lesser extent, in posterior parietal regions bilaterally; mild hypoperfusion in
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Neurosyphilis is rather an unusual cause of dementia characterized by a rapidly progressive course and psychiatric symptoms. Diagnosis of neurosyphilis should be suspected in the presence of a global cognitive impairment consisting in disorientation, amnesia and severe impairment of speech and judgement and psychiatric symptoms such as depression,...
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Context 1
... a Mini Mental Status Examination (MMSE) score of 14/30. EEG showed diffuse slow activity prominent in left frontotemporal regions. A neurodegenerative dementia was suspected and, therefore, laboratory and imaging diagnostic workup was performed. Magnetic resonance imaging (MRI) revealed mild cortical atrophy more marked in mesial temporal lobes (Fig. 1a) and cerebral single-photon emission computed tomography (SPECT) disclosed a diffuse reduction of per- fusion in frontal and left parieto-temporal lobes (Fig. 1b). Serum Venereal Disease Research Laboratory (VDRL) test was reactive 1:256 and Treponema Pallidum Particle Agglutination (TPPA) positive 1:20,480; HIV tests were negative. CSF ...
Context 2
... was suspected and, therefore, laboratory and imaging diagnostic workup was performed. Magnetic resonance imaging (MRI) revealed mild cortical atrophy more marked in mesial temporal lobes (Fig. 1a) and cerebral single-photon emission computed tomography (SPECT) disclosed a diffuse reduction of per- fusion in frontal and left parieto-temporal lobes (Fig. 1b). Serum Venereal Disease Research Laboratory (VDRL) test was reactive 1:256 and Treponema Pallidum Particle Agglutination (TPPA) positive 1:20,480; HIV tests were negative. CSF analysis showed hyperproteinorrachia (1.21 g/L), mild pleocytosis (20 leukocytes/mm 3 , mainly lymphocytes) and positive OB. Tau protein levels were 492 pg/mL ...
Context 3
... depressed mood and global cognitive impairment, particularly of verbal and visual memory and conceptual reasoning. He exhibited also mild deficits in tests exploring attention, visual-spatial exploration, verbal fluency and language skills. MMSE resulted 16/30. EEG showed slightly irreg- ular background activity. Although brain MRI was nega- tive (Fig. 1c), brain SPECT revealed hypoperfusion in middle-frontal regions and, to a lesser extent, in posterior parietal lobes, in right temporal region and in the head of the left caudate nucleus (Fig. ...
Context 4
... verbal fluency and language skills. MMSE resulted 16/30. EEG showed slightly irreg- ular background activity. Although brain MRI was nega- tive (Fig. 1c), brain SPECT revealed hypoperfusion in middle-frontal regions and, to a lesser extent, in posterior parietal lobes, in right temporal region and in the head of the left caudate nucleus (Fig. ...
Context 5
... left side); saccadic eye movements were fragmented and sphincterial control compromised. Owing to his psychiatric features neuropsychological evalu- ation was impossible. EEG was diffusely slow. Brain MRI revealed marked hyperintensity of frontal periventricular white matter on T2 and fluid attenuated inversion recovery (FLAIR) weighted images (Fig. 1e). Serum VDRL was positive 1:64 and serum TPPA [1:20,480. HIV tests were negative. CSF examination revealed mild hyperproteinorra- chia (0.94 g/L), endogenous synthesis index of 5.45, elevated immunoglobulins, positive OB and VDRL positive 1:8. Tau protein was 257 pg/mL and 14-3-3 protein positive. CSF cytology disclosed pleocytosis ...
Context 6
... a decrease in protein content (0.56 g/L) and an increase in leukocytes (42/lL); VDRL resulted positive 1:1. EEG showed theta-delta slowing prevailing on frontal regions. MRI was unmodified. SPECT disclosed diffuse cortical hypoperfusion (worse in anterior and left cortical regions) except for visual area, basal ganglia and subtentorial cortex (Fig. ...
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Purpose:
Transient Epileptic Amnesia (TEA) is a form of adult onset temporal lobe epilepsy characterised by ictal amnesia. The amnesic seizures are often accompanied by interical memory disturbance, involving autobiographical amnesia and accelerated long-term forgetting. Short-term follow-up studies suggest a relatively stable cognitive profile on...
We describe a patient who developed significant cognitive decline with profound amnesia following non-dominant temporal lobectomy for refractory seizures, in whom the original suspicion of structural pathology was revised following the discovery of clinical and neuropathological markers of inflammation, neuropsychological evidence of bilateral invo...
Citations
... It is characterized by sensorimotor symptoms such as abnormal gait, tremors, and numbness of the lower limbs accompanied by cognitive and mood dysfunction such as confusion, poor concentration, depression, and irritability. Interestingly, several cases of dementia caused by late neurosyphilis have been reported [248][249][250][251][252][253][254][255][256][257][258][259]. Commonly the patients are around 40-60-year-old at the time of diagnosis (early-onset for dementia) and they display a variety of neurological symptoms such as rapid cognitive decline, behavioral changes, and psychosis. ...
... Commonly the patients are around 40-60-year-old at the time of diagnosis (early-onset for dementia) and they display a variety of neurological symptoms such as rapid cognitive decline, behavioral changes, and psychosis. In some patients, the symptoms ameliorate after treatment with antibiotics [248][249][250][251][252][253][254][255][256][257][258][259]. Thus, syphilis should be considered as a cause for dementia-like symptoms in infected individuals. ...
Central nervous system infections have been suggested as a possible cause for neurodegenerative diseases, particularly sporadic cases. They trigger neuroinflammation which is considered integrally involved in neurodegenerative processes. In this review, we will look at data linking a variety of viral, bacterial, fungal, and protozoan infections to Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis and unspecified dementia. This narrative review aims to bring together a broad range of data currently supporting the involvement of central nervous system infections in the development of neurodegenerative diseases. The idea that no single pathogen or pathogen group is responsible for neurodegenerative diseases will be discussed. Instead, we suggest that a wide range of susceptibility factors may make individuals differentially vulnerable to different infectious pathogens and subsequent pathologies.
... bipolar affective disorder), toxicity associated with medications/substance use, and neurosyphilis. 44 Movement abnormalities are often seen in AE, including FBDS in LGI1 antibody-associated encephalitis, and choreoathetosis, catatonia, and orofacial dyskinesias in anti-NMDA-receptor encephalitis. 8,24 However, these abnormalities are also recognized early in the clinical course in several other potentially treatment-responsive and non-responsive causes of RPD. ...
Background
Rapidly progressive dementia (RPD) includes patients with less than two years from the onset of cognitive impairment to incapacitation due to dementia. Although RPD is often associated with fatal neurodegenerative diseases, including early‐onset Alzheimer disease or Creutzfeldt‐Jakob disease, treatable forms of RPD are increasingly recognized. Early recognition of patients with potentially treatable causes of RPD is key to the timely provision of therapies required to achieve the best possible long‐term outcomes.
Method
155 patients with RPD were prospectively enrolled from February 2016 to August 2022 via two tertiary care centers. Etiologic diagnoses were independently assigned by two neurologists with good agreement (>90%). Causes of RPD were further classified as treatment‐responsive or nonresponsive, referencing the extant literature. Demographic, clinical, and paraclinical features associated with treatable causes of RPD were identified using stepwise multivariate logistic regression and validated with 5‐fold cross validation.
Result
87/155 patients (56.1%) had a potentially treatable cause of RPD, including autoimmune/inflammatory disease (n = 52, 59.8%), vasculitis (n = 13, 14.9%), primary psychiatric disease (n = 4, 4.6%), or nutritional deficiency (n = 4, 4.6%). Multivariable analyses identified seven features that were independently associated with treatment‐responsiveness: age‐at‐symptom onset (OR: 0.62 per decade, 95%CI: 0.42‐0.93), seizures (OR: 9.81, 95%CI: 2.84‐33.89), MRI suggestive of autoimmune encephalitis (OR: 23.08, 95%CI: 2.28‐233.40), CSF white blood cell count ≥10 cells/mm ³ (OR: 32.24, 95%CI:5.80‐179.21), movement abnormalities (OR: 4.99, 95%CI: 1.76‐14.10), presence of disease‐associated tumor (OR: 13.82, 95%CI: 2.25‐85.11), and mania (OR: 18.47, 95%CI: 1.76‐193.61). Model performance was excellent (c‐statistic = 0.88, 95%CI: 0.82‐0.94; p<0.001): 71 patients (81.6%) with potentially treatable causes of RPD and 56 patients (82.4%) with non‐treatable causes of RPD were correctly classified (PPV = 85.5%; NPV = 77.8%).
Conclusion
Treatment‐responsive causes of RPD were common in our series. Younger age, seizures, movement abnormalities, or mania at presentation, and paraclinical tests suggesting inflammation (MRI or CSF) or tumor in patients with RPD should prompt consideration of treatable causes of RPD and initiation of treatment when indicated.
... 7,37 Mania may be observed at presentation in AE, especially in patients with anti-NMDA-receptor encephalitis; 43 however, the detection of mania in RPD should suggest a broader differential, including primary psychiatric disease (eg, bipolar affective disorder), toxicity associated with medications/ substance use, and neurosyphilis. 44 Movement abnormalities are often seen in AE, including faciobrachial dystonic seizures in LGI1 antibody-associated encephalitis, and choreoathetosis, catatonia, and orofacial dyskinesias in anti-NMDA-receptor encephalitis. 8,24 However, movement abnormalities are also recognized early in the clinical course in several other potentially treatment-responsive and nonresponsive causes of RPD. ...
Objective
To improve the timely recognition of patients with treatment‐responsive causes of rapidly progressive dementia (RPD).
Methods
Two‐hundred twenty‐six adult patients with suspected RPD were enrolled in a prospective observational study and followed for up to two years. Diseases associated with RPD were characterized as potentially treatment‐responsive or non‐responsive referencing clinical literature. Disease progression was measured using Clinical Dementia Rating® Sum‐of‐Box scores. Clinical and paraclinical features associated with treatment responsiveness were assessed using multivariable logistic regression. Findings informed the development of a clinical criterion optimized to recognize patients with potentially treatment‐responsive causes of RPD early in the diagnostic evaluation.
Results
One‐hundred fifty‐five patients met defined RPD criteria, of whom 86 patients (55.5%) had potentially treatment‐responsive causes. Median (range) age‐at‐symptom onset in patients with RPD was 68.9 years (22.0‐90.7), with a similar number of males and females. Seizures, tumor (disease‐associated), MRI suggestive of autoimmune encephalitis, mania, movement abnormalities, and pleocytosis (≥10 cells/mm ³ in CSF) at presentation were independently associated with treatment‐responsive causes of RPD after controlling for age and sex. Those features at presentation, as well as age‐at‐symptom onset < 50 years (i.e., STAM 3 P), captured 83/86 (96.4%) cases of treatment‐responsive RPD. The presence of ≥3 STAM 3 P features had a positive predictive value of 100%.
Interpretation
Selected features at presentation reliably identified patients with potentially treatment‐responsive causes of RPD. Adaptation of the STAM 3 P screening score in clinical practice may minimize diagnostic delays and missed opportunities for treatment in patients with suspected RPD.
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... Late neurosyphilis may also present as tabes dorsalis, which results in degeneration of the nerve cells in the dorsal columns of the spinal cord that carry sensory information to the brain [5]. the involvement of personality, affect, reflexes, eye, sensorium, intellect, and speech [6]. As a consequence of brain parenchymal invasion by spirochetes, late neurosyphilis can notably mimic various psychiatric conditions -some of which include depression, mania, psychosis, hallucinations, delusions, elation, dementia, and schizophrenia-like illness [6]. ...
... the involvement of personality, affect, reflexes, eye, sensorium, intellect, and speech [6]. As a consequence of brain parenchymal invasion by spirochetes, late neurosyphilis can notably mimic various psychiatric conditions -some of which include depression, mania, psychosis, hallucinations, delusions, elation, dementia, and schizophrenia-like illness [6]. The frequency of psychiatric signs and symptoms associated with neurosyphilis ranges from 33% to 86% as reported in the literature [7]. ...
Neurosyphilis is an infection of the central nervous system caused by the spirochete, Treponema pallidum. New syphilis infections have been increasing around the world each year. This disease was much of a concern in the pre-penicillin era, where when left untreated many cases progressed to tertiary syphilis which can commonly manifest as neurosyphilis. Of particular interest, neurosyphilis has been linked to masquerading itself as various psychiatric conditions. This narrative review focuses on exploring psychiatric manifestations of neurosyphilis as well as the importance of screening in psychiatric settings and clinicians maintaining high clinical suspicion of the disease. A systematic search was conducted for published articles from 2003 to 2023 using PubMed, EMBASE, and Google Scholar. A total of 66 articles met the criteria and were used for detailed analysis, where psychiatric manifestations and clinical progression of patients were discussed in detail. Psychiatric manifestations that were explored include dementia, delirium, depression, mania, personality changes, and psychosis. One of the most common manifestations of neurosyphilis appears to be severe neurocognitive impairment. There are also rare psychiatric conditions neurosyphilis mimics that have been described in literature such as Capgras syndrome and Geschwind syndrome. A narrative review of the literature revealed a low level of clinical awareness of neurosyphilis as a possible etiology of various psychiatric disorders. This resulted in delayed or inaccurate diagnosis and consequently delayed initiation of adequate treatment. Considering that many psychiatric manifestations of neurosyphilis are reversible with proper treatment, it is imperative to implement routine screening for syphilis among psychiatric patients.
... N eurosyphilis is the severe consequence of the syphilis infection in the CNS-an event that can occur at any stage of the infection (Conde-Sendín et al, 2004;Ghanem, 2010). The most common presentations of neurosyphilis include cognitive impairment mimicking degenerative dementias and/or psychiatric disorders, ranging from mood abnormalities to severe psychosis (Mahajan et al, 2017;Mukku et al, 2019;Rao et al, 2015;Stefani et al, 2013;Tatar et al, 2014;Verjans et al, 2016;Yanhua et al, 2016;Zheng et al, 2011). In some cases, limbic encephalitis-like or acute disseminated encephalomyelitis-like phenotypes have been described (Derouich et al, 2013;Serrano-Cardenas et al, 2018;Skalnaya et al, 2019;Xiang et al, 2013). ...
We present the case of a man exhibiting a clinical phenotype of behavioral variant of frontotemporal dementia (bvFTD). The man had developed psychiatric disturbances with verbal aggressiveness over a few months, followed by cognitive and frontal behavioral disorders, fulfilling the clinical criteria for bvFTD. Atrophy and hypometabolism in frontotemporal regions were consistent with the diagnosis. However, serum-screening exams for syphilis infection were positive, and CSF analysis, despite a negative Venereal Disease Research Laboratory Test, suggested the diagnosis of neurosyphilis. After specific antibiotic therapy, the man's behavioral abnormalities and cognitive deficits notably improved, confirming neurosyphilis as the cause of the clinical phenotype. The cognitive deficits completely recovered 1 year post therapy and remained stable for 2 years. After ∼2½ years from the first treatment, the man's behavioral disorders mildly worsened, at which time we re-evaluated him. His cognition was stable, and a positive Venereal Disease Research Laboratory Test confirmed the diagnosis of neurosyphilis. With this case, we demonstrated that in some instances, neurosyphilis can mimic frontotemporal dementia. As a cause of treatable dementia, it should be considered in the differential diagnosis of bvFTD, particularly when psychiatric symptoms and a rapid cognitive decline are noted, even in the presence of brain atrophy and/or hypometabolism.
... Our results are in agreement with previous SPECT findings of decreased rCBF in the frontal regions in patients with general paresis (15)(16)(17)(18), which is the most common form of neurosyphilis presenting with cognitive impairment and psychiatric symptoms (19). These cases also reported decreased rCBF in the temporal regions (15)(16)(17)(18), which was less prominent in our study. ...
... Our results are in agreement with previous SPECT findings of decreased rCBF in the frontal regions in patients with general paresis (15)(16)(17)(18), which is the most common form of neurosyphilis presenting with cognitive impairment and psychiatric symptoms (19). These cases also reported decreased rCBF in the temporal regions (15)(16)(17)(18), which was less prominent in our study. In contrast, there are single-case reports that showed increased rCBF in the temporal lobe (20) and frontal and temporo-occipital regions (21). ...
Objective: Clinical and radiological findings on neurosyphilis are fairly non-specific and there is a paucity of functional neuroimaging studies on neurosyphilis other than case reports and case series. The purpose of this study was to investigate brain perfusion abnormalities in patients with neurosyphilis.
Methods: Four HIV-negative neurosyphilis patients and 4 healthy controls underwent clinical evaluation, brain technetium-99m ethyl cysteinate dimer (99mTc-ECD) single-photon emission computed tomography (SPECT) imaging, and neuropsychological assessments which included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Clinical Dementia Rating—Sum of Boxes (CDR-SOB), and Global Deterioration Scale (GDS). Voxel-wise differences in regional cerebral blood flow were compared between the two groups.
Results: Neuropsychological test results indicated cognitive impairment in all patients. SPECT analysis revealed multifocal hypoperfusion predominantly in the frontal, insular, and posterior cingulate regions in neurosyphilis patients compared with healthy controls (family-wise error corrected p < 0.05).
Conclusions: Together with previous findings, our results suggest that the hypoperfusion in the frontal, insular, and posterior cingulate regions may reflect cognitive impairments observed in neurosyphilis patients. Further studies with larger samples are needed to confirm our findings.
... Even after several years in the latent phase, the infection can re-manifest itself through sensory ataxia and intestinal/bladder dysfunction, a phenomenon called Tabes dorsalis or general paralysis. Although less frequent, it may also present in the form of rapidly progressive dementia [4] . ...
Although worldwide prevalence has decreased with the onset of antibiotic therapy, syphilis plays an important role in modern medical and psychiatric practice. Neurosyphilis, a Central Nervous System infection caused by the spirochete Treponema pallidum, is a serious pathology that leads to deterioration of the disease with a significant impact on his life and also on the caregivers'. The authors propose a brief review of the topic based on the clinical cases of two patients admitted to sudden manifestations of cognitive and behavioral changes diagnosed with neurosyphilis, reflecting on the importance of the exclusion of organic causes and the treatment of psychiatric symptomatology. These events are usually diagnosed as rapidly progressive dementia, which may be due to different causes, so that the psychiatrist must assume a high degree of suspicion. Although there is a standard treatment with penicillin for neurosyphilis, in the current literature there is no evidence regarding the treatment of its psychiatric manifestations, altough there is an apparent benefit in the judicious use of antipsychotics.
... Neuroimaging examinations in patients with NS are important for the differential clinical diagnosis and follow-up, with the presentations being diverse [6]. Although several studies have analyzed clinical and laboratory characteristics of asymptomatic and symptomatic neurosyphilis patients, to the best of our knowledge, no systematic study has investigated neuroimaging changes after anti-syphilitic treatment [7][8][9][10]. Herein, we retrospectively reviewed 102 patients with NS who were examined at our center and made comparisons between asymptomatic and symptomatic NS patients. ...
IntroductionMany studies have explored the imaging characteristics of patients with neurosyphilis, but no systematic study has been made on the neuroimaging changes after anti-syphilitic treatment. The purpose of this study was to examine neuroimaging differences before and after treatment, comparing patients with asymptomatic and symptomatic neurosyphilis.MethodsA total of 102 patients with neurosyphilis, including 60 cases of symptomatic neurosyphilis and 42 cases of asymptomatic neurosyphilis, were identified between December 2012 and June 2019. Their demographics, medical histories, serological tests of peripheral blood and cerebrospinal fluid, and especially neuroimaging features before and after anti-syphilitic treatment were collected and analyzed.ResultsThe patients presented with variable clinical and neuroimaging features, including cerebral infarction or hemorrhage, atrophy, demyelination, arteritis, encephalitis, and hippocampal sclerosis. A total of 29 neuroradiological re-examinations were performed in 19 patients treated with anti-syphilitic medicine. The results indicated that some patients still presented neuroradiological progression after treatment, including 42.1% showing infarction lesions, 47.4% mild to severe brain atrophy, and 15.8% white matter demyelination.Conclusion
The clinical and neuroimaging features of neurosyphilis patients are diverse, and their follow-up neuroimaging continued to show progression even with standardized treatment.
... [3] Neurosyphilis is rather an unusual cause of dementia characterized by a rapidly progressive course and psychiatry symptoms. [4] Paretic neurosyphilis or general pareses usually develop 15-20 years after infection. PARESIS is an acronym ((involvement of Personality, Affect, Reflexes, Eye, Sensorium, Intellect and Speech). ...
... CSF examination was mandatory in neurosyphilis diagnosis. [4] Asymptomatic cases and cases with ill-defined syndrome become more common than the classic presentation of tabes dorsalis and general paresis. In this article, we present a case of neurosyphilis with progressive cognitive changes and intractable behavior and psychiatric problems whose primary and secondary phases were not detected. ...
... [1] Rapidly progressive dementia (RPD) associated with neuropsychiatric symptoms is the most common form of presentation of general paresis and includes a series of disturbances such as personality changes, amnesia, delusions, hallucinations and delirium. [4] No clinical or dermatological symptoms or sign was found related to primary and secondary stages of syphilis in our patient's history. It is noteworthy that clinical picture emerged with tertiary syphilis first. ...
The manifestations of CNS syphilis are unfamiliar to a differential of patients with dementia to many physicians today as of the relative rarity of this condition. This is a classical case report of a patient with syphilis and dementia in a 55-year-old female. General paresis of insane is a progressive disease of the brain leading to mental and physical worsening. It is important to consider tertiary syphilis in the differential diagnosis of dementia. Conventional presentations of neurosyphilis such as tabes dorsalis and general paresis of insane are read in textbooks only and rarely encountered in clinical practice in the 21st century.
... Rehabilitation and cognitive remediation is necessary in patients with cognitive sequelae of neurosyphilis. However, the few studies that have addressed neuropsychological assessment of patients with cognitive impairments due to neurosyphilis are silent on this approach to treatment of this condition (13,19). The absence of literature describing cognitive rehabilitation for persons with neurosyphilis may be related to a presumption that cognitive impairments due to such infections remit with antibiotic therapy (20). ...
Subacute cognitive disorders are frequently encountered in clinical practice, and many pathologies result in such pre- sentations. Consequently, prompt and precise etiologic di- agnosis is necessary because, in some cases, introducing treatments may reverse or prevent further progression of cognitive impairment. The differential diagnosis of subacute cognitive disorders
is broad and requires careful consideration. Among the causes of such disorders are: Creutzfeldt-Jakob disease, a brain disorder resulting in a rapidly progressing dementia syndrome, myoclonus, psychiatric disorders, and visual hallucinations. Other etiologies include toxins and vitamin deficiencies, Wernicke-Korsakoff syndrome, psychiatric pathologies (e.g., bipolar or unipolar disorder and chronic psychosis, dissociative or nondissociative), and epileptic syndromes and nonconvulsive status epilepticus. Moreover, autoimmune encephalitis can cause cognitive dysfunction, often with co-occurring depressive syndrome, anxiety, and irritability (1). Patients with infectious encephalitis may present with symptoms of cognitive dysfunction as well. Here, we present a case of neurosyphilis in an HIV-negative male patient, with discussion of clinical manifes- tations and neuroimaging modification.
