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The Clinical Presentation and Imaging Manifestation of Psychosis and Dementia in General Paresis: A Retrospective Study of 116 Cases
Dong Zheng, M.D.; Daoyou Zhou, M.D.; Zhongyan Zhao, M.D.; Zhonglin Liu, M.D.; Songhua Xiao, M.D.; Yigang Xing, M.D.; William Z. Suo, M.D.; Jun Liu, M.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 2011;23:300-307.
View Author and Article Information

From the Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China 510120; Department of Neurology, Guangzhou Brain Hospital, China 510370; Department of Neurology, Guangdong Province Hospital of Traditional Chinese Medicine, Guangzhou, China 510120; Laboratory for Alzheimer's Disease and Aging Research; Veterans Affairs Medical Center, KS City, MO, United States; Departments of Neurology, and Molecular, and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA.

Correspondence: Dr. Jun Liu; docliujun@hotmail.com (e-mail).

Received June 5, 2010; December 8, 2010; Accepted January 1, 2011.

In recent years, occurrence of “general paresis (GP)” has increased significantly because of the increasing incidence of syphilis in China. Early diagnosis plays a very important role for effective treatment. Incidence is becoming extensive enough to warrant an updated investigation of the clinical characteristics of GP. The authors retrospectively reviewed 116 cases of GP in Guangzhou, China, and analyzed its incidence and clinical appearance, as well as the characteristics of EEG, neuroradiology, serum, and cerebrospinal fluid examinations. Of the 116 GP patients, clinical symptoms presented frequently on admission were a variety of psychiatric-behavioral symptoms and varying degrees of dementia. Positive sucking reflex was the most common sign, as well as hyperreflexia and Argyll-Robertson pupil. EEG data mainly showed slightly abnormal EEG activity, with increased δ waves. Focal atrophy in one or multiple cerebral regions was evident on neuroimage. The prevalence of GP extends to various social strata or classes, with clinical presentation varying considerably among patients. For patients with progressive cognitive and behavioral deterioration, accompanied with psychotic and/or affective behavioral disorders or cerebral atrophy of unknown cause, general paresis should be considered.

Abstract Teaser
Figures in this Article

After continuous decline throughout the 1950s, the incidence of sexually transmitted diseases (STDs) in the People's Republic of China was virtually eliminated by 1964 across the country. However, it has shown a rapid and substantial increase during the last 20 years because of the “political reform and opening-up” policies since the 1980s. Similarly, incidence of syphilis increased approximately 20 times from 1989 to 1998, at an average annual increase of 52.7%.1 This introduced a big health problem that has been noticed by Chinese and foreign health researchers. Guangdong province, as the forefront of the “reform and opening,” has therefore had the worst prevalence of STDs in the country.

General paresis (GP) is a clinical type of late-stage syphilis and neurosyphilis. Diagnosis of GP depends on clinical evaluation, serologic testing, and cerebrospinal fluid (CSF) examination. Clinical presentation of GP varies considerably among patients, and diagnosis may fall to the general physician, geriatrician, neurologist, psychiatrist, or venereologist. Clinical recognition of GP may be easy or difficult. There is no gold standard for its diagnosis at present, which often results in undue delayed diagnosis and causes serious consequences.

It is therefore necessary to investigate the clinical characteristics of GP in hope to improve its early diagnosis. For this purpose, we collected data on demographic characteristics, clinical neuropsychological, EEG, neuroradiological, serum, and CSF examination profiles of GP patients in several neurological units in the south of China.

We retrospectively reviewed 116 GP cases diagnosed between January 2004 and December 2009 at Guangzhou Brian Hospital, the second Affiliated Hospital of Sun Yat-Sen University and Guangdong Province Hospital of Traditonal Chinese Medicine in Guangzhou, China. The case records were carefully searched for all available data on the course of the illness during the stay in the hospital. All patients were diagnosed with GP on the basis of clinical features and the etiological tests in serum and CSF. Particular interest was directed toward obtaining the incidence and nature of clinical signs and symptoms. EEG, neuroradiological, and CSF examination results were included as well. Furthermore, because some patients were uncooperative, certain information was obtained from their relatives at admission.

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Epidemiological Analysis

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Age and Sexuality

Age range on admission to the hospital was 30 to 76 years (mean: 45.6 [standard deviation {SD}: 5.8]) for men, and 28 to 73 years (mean: 50.2 [SD: 9.6]) for women. The peak age at symptom onset for both sexes fell within an age range of 50 to 65 years. The sex distribution was 104 men and 12 women.

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Social Status and Occupations

An analysis of social status and occupations revealed that the population of these patients included 13 semiskilled/unskilled workers (11.21%), 20 “peasants,” including peasant workers who worked on construction sites in cities (17.24%), 21 individual business owners (18.10%), 10 salesman (8.62%), 10 civil servants (8.62%), 11 drivers (9.48%), 3 teachers (2.59%), 3 nightclub waiters (2.59%), 3 housewives (2.59%), 22 with irregular jobs (18.97%; Table 1).

 
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History of Contact

All female patients denied a promiscuous sex life or history of involvement in sex work. Among male patients, 61 patients admitted a promiscuous sex life, including a history of using prostitutes; 25 patients denied these; and the rest of the male patients (N=37) could not provide any distinct information either because of psychosis or severe decrease in their cognitive functioning.

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Comorbidity With Other Sexually-Transmitted Diseases

Human immunodeficiency virus (HIV)-related antibody was examined, and all patients were negative for HIV antibody. Fifteen patients had once been infected by the bacterium Neisseria gonorrhoeae, but had already been cured.

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Clinical Characteristics

Although there was considerable overlap, because many patients had features of more than one syndrome, it was possible to divide the cases into different syndromes. The most frequent clinical symptoms presented on admission were a wide variety of psychiatric-behavioral symptoms, including emotional problems (92.24%; 107/116) and personality changes (87.93%; 102 patients), abnormal behavior (84.48%; 98/116), delusions (38.79%; 45/116), and hallucinations (12.93%; 15/116).

The other most frequent and important clinical feature of general paresis patients was cognitive impairment. Seventy-five patients were given the Mini-Mental State Exam (MMSE) at admission, and 85.33% of patients (64/75) showed different degrees of decline of intelligence and memory; their MMSE scores ranged from 3 to 19 (mean: 14.7 [SD: 3.2]). Incontinence of feces and urine (35.34%; 41/116), dysrhythms of the sleep–wake routine (25%; 29/116), epileptic seizures (16.38%; 19 patients) were also common symptoms. Symptoms such as palsy, unsteady gait, coughing when drinking, dysarthria, and tremors could be observed as well (Table 2).

 

We further investigated the details of the common symptoms in those with psychiatric-behavioral symptoms. We found that in cases with emotional problems, 83.18% of patients (89/107) of patients tended to switch from one extreme to another; they were moody and unpredictable. Meanwhile, 63.55% of patients (68/107) of patients were characterized by childishness; 33.64% (36/107) showed apathy; 22.43% (24/107) appeared euphoric; 14.02% (15/107) showed depression; and 13.08% (14/107) showed forced crying and laughing. For patients with abnormal behavior, aggressive behavior toward relatives and others was the most distinct symptom, reaching 68.37% (67/98). Delusions of persecution and delusions of grandeur were the most common symptoms in patients with delusions, reaching 86.67% (39/45) and 28.89% (13/45), respectively. The distinct differences of delusions between GP and schizophrenia were that delusions in GP patients were not as systematic as those in patients with schizophrenia. Regarding hallucinations, the incidence of auditory hallucinations was much higher than visual hallucinations: 80% (12/15) and 20% (3/15), respectively (Table 3).

 
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TABLE 3.Details of Psychiatric-Behavioral Symptoms
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Main Signs

Many patients had more than one clinical sign, so there was overlap of patients' main signs. The most common sign was positive sucking reflex, which appeared in 112 of the 116 patients (96.55%). This indicated severe damage to the frontal lobe, and was in accordance with their abnormal emotion and psychosis. Although Argyll-Robertson pupil is an important and typical sign of GP, its incidence here was only 31.03% (36/116). The other signs included 75% with hyperreflexia (87/116); 23.28% with pseudobulbar palsy (27/116); 22.41% with positive Babinski's sign (26/116); 19.83% with cerebellar ataxia (23/116); 14.66% with paresthesia (17/116); 12.07% with paresis of limbs (14/116); 2.59% with optic atrophy (3/116); 1.72% with sensory ataxia (2/116); and 1.72% with ophthalmoplegia externa (2/116); (see Table 4).

 
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TABLE 4.Details of Clinical Signs (N=116)
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Routine CSF Examination

Routine CSF examination revealed a nonspecific inflammatory response in most patients. An increased concentration of globulin was seen in 89 patients (76.72%) on admission. Increased white-cell count was detected in 56 patients (48.28%), and decreased concentration of chloride was found in 9 patients (7.76%) on admission. Pressure level of CSF and concentration of glucose were normal in all patients.

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Syphilis Pathogen Examination

Treponema Pallidum Hemagglutination Assay (TPHA) and Syphilis Toluidine Red Untreated Serum Test (TRUST) were administered immediately on admission. Both tests were positive for serum samples in 100% of the patients on admission. As for CSF samples, TPHA was positive in all 116 patients (100%), while TRUST was positive in 100 patients (86.21%). There was a statistically significant difference between the positive rates of TPHA and TRUST in CSF by chi-square statistic (χ2=4.17; p<0.05).

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EEG Examination

EEG (electroencephalographic) data were only available in 102 cases; 79.41% of patients (81/102) showed slightly abnormal EEG activity, with increased δ waves; 13.73% of patients (14/102) showed moderate-to-severe abnormal EEG activity, including single epileptiform discharge, in 4.9% patients (5/102), slight-to-moderate elevation of diffuse slow electrical activity in 1.96% of patients (2/102), and severe asymmetrical brain electrical activity in 6.86% of patients (7/102).

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Neuroimaging Examination

MRI/CT scan was available for all patients. Focal atrophy in one or multiple cerebral regions was evident in 87.07% (101/116); frontal: 84.48% (98/116); temporal: 84.48% (98/116); parietal: 56.03% (65/116); occipital: 4.31% (5/116); and cerebellar regions: 3.45% (4/116). Concomitant small vascular lesions and/or demyelinating lesions in white matter were observed in 84.48% of patients (98/116). Thickened cerebral dura mater was seen in 27.59% of patients (32/116), and hydrocephalus was seen in 23.28% (27/116). Only in 10.34% of patients (12/116) was the exam normal (Table 5).

 
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Clinical Misdiagnosis

Forty-two cases had once been misdiagnosed, and the rate of clinical misdiagnosis was 36.21%. Among these, 16.38% of cases (19/116) were clinically misdiagnosed as schizophrenia; 6.03% (7/116) cases as depression; 4.31% (5/116) as vascular dementia; and 2.59% (3/116) as viral encephalitis. The duration of the misdiagnosis lasted from 1 month to 24 months (mean: 8.2 [SD: 4.6 months]).

GP is caused by syphilis infection; it is also known as paralytic dementia, Bayle's disease, parenchymal syphilis, and symptomatic neurosyphilis. It is a neuropsychiatric disorder affecting the brain and CNS, and typically presents as progressive dementia, beginning 15–20 years after original infection (range: 3–30 years).

Evidence shows that syphilis has become a major public health problem again in recent decades. From 1988 to 1995, a persistently growing number of new cases of syphilis in the world was observed.2 In the United States, rates of primary and secondary syphilis again began to rise in 2001 after a decade of decline.3 In San Francisco, the increased incidence of early syphilis has been accompanied by increasing rates of neurosyphilis,4 and HIV infection also increases the risk of neurosyphilis.5 Similar trends have also been observed in Canada and Europe.6 In China, since the reform and opening-up policies of the early 1980s, STDs have been gradually recognized as public health problems, and the incidence of syphilis has increased steadily.1 In 1993, the reported total rate of cases of sysphilis in China was 2 cases per million people, whereas primary and secondary syphilis were 57 cases per million people in 2005. The rate of congenital syphilis increased drastically, with an average yearly rise of 71.9%, from 0.1 per million live births in 1991 to 196.9 per million live births in 2005.7 GP increased correspondingly after several years of incubation period; this is considered to be a “treatable” dementia because it can be treated with antibiotics, mainly penicillin.8 However, early diagnosis and treatment are very important.

The diagnosis of GP could be differentiated from other known psychoses by characteristic abnormality in eye pupil reflexes, development of muscular reflex abnormalities, seizures, memory impairment (dementia), and other signs of relatively pervasive neurocerebral deterioration. Eventually, the patients became completely incapacitated, bedridden, and die, the process taking about 3-to-5 years, on average.911 Clinicians need to recognize all the features of the clinical picture in order to correctly identify the GP patients at the early stage of the disease and design appropriate clinical treatments.

In our study, we found that neurosyphilis occurred more often in male than female patients, with a sex ratio of 8.67 to 1, which was higher than in previous reports.12 Furthermore, GP affected mainly young adult men, raising the question of whether it is due to an increasing incidence of homosexual behavior among men. About half of the patients had identified promiscuous sexual activity and/or history of frequenting prostitutes. The group suffering with GP were persons engaged in a variety of occupations. Among them, a large portion was mainly from lower social classes, including those with irregular work, nightclub waiters, low-skilled workers, poorly educated (junior middle school education or less), peasant or peasant workers, small-business owners, and laborers. It is worth noting that the analysis of social status revealed that some well-educated persons, such as teachers and civil servants, were also involved. This indicates that the prevalence of GP has extended to various social strata or classes, which is consistent with the report by Lin et al.13 The prevalence of GP is a very serious issue now in China.

It has been reported that HIV infection has a strong epidemiological association with neurosyphilis. Analysis of cases with dual infection with Treponema pallidum and HIV indicated that HIV infection may accelerate the course of syphilis and that the presence of syphilis may also have an influence on progression of chronic HIV infection to AIDS.5,14 Yet, in our study, no GP patients were simultaneously infected by HIV, maybe because of lower incidence of HIV infection in certain populations in China. Nevertheless, we strongly suggest that all of the patients with syphilis should be examined for the presence of HIV infection.

The most common symptom in our findings was emotional problems, followed by personality changes, different degrees of cognitive deterioration, abnormal behaviors, psychiatric symptoms, including delusions and hallucination, incontinence of feces and urine, dysrhythmia of the sleep–wake routine, and epileptic seizures. Other, lower incidence, symptoms, such as palsy, unsteady gait, coughing when drinking, dysarthria, and tremors, could also be observed in our study. Dawson-Butterworth and Heathcote15 reported that the incidence of dementia in GP patients is about 60%–80%. It was 85.33% in our study. The incidence of personality changes and abnormal behavior were similar to those of dementia, reaching 87.93% and 84.48%, respectively, which were higher than their report. As for the incidence of emotional problems, in our report, it was 92.24%, which was much higher than the 17% reported by them. The reason may be that emotional problems are now being taken more seriously by neuropsychologists, and there are more precise neuropsychological scales now than there were then. Epileptic seizures and limb pain, which were seldom reported before, were 16.38% and 10.34%, respectively, in our study, indicating that clinical manifestation of the GP developed in a diversified forms and complicated ways.

We further investigated the details of the common symptoms in those with psychosis. Changeable mood was the most common symptom and occurred in 83.18% of patients with emotional problems. The incidence of depression and euphoria tended to remain constant over the years, at 10% and 20.69%, respectively. Auditory hallucination was the most outstanding symptom in patients with hallucinations. Dewhurst16 stated that grandiose delusion was not one of the most commonly presenting features of cerebral syphilis. He reported 10.9% for his patients; data from Chia and Tsoi17 indicated it was 10%; Dawson-Butterworth and Heathcote15 gave a figure of 9.3%; and our investigation was also in agreement and yielded 11.21%. It has been reported that men tended to be more aggressive than women on admission. Dawson-Butterworth and Heathcote reported that the total incidence is around 30%, and this uncontrolled behavior subsided with treatment, but tended to recur after a few years in the same proportions as before.15 Chia and Tsoi17 reported 44% of patients with aggressive behavior. In our study, there was a higher incidence of aggression; it reached 57.76%, which implies that GP patients might be potentially harmful to society.

The most common sign, although seldom noticed by doctors, was positive sucking reflex. There were 112 cases in a total of 116 patients, which indicated severe damage to the frontal lobe, and is in accordance with patients' abnormal emotions and psychosis. Argyll-Robinson pupils are bilaterally small pupils that constrict when the patient focuses on a near object (they “accommodate”), but do not constrict when exposed to bright light (they do not “react” to light). Although the underlying pathophysiologic mechanism is unclear, research has implicated that the rostral midbrain in the vicinity of the sylvian aqueduct of the third ventricle might be the most likely region of damage. Argyll-Robinson pupil is an important and typical sign of neurosyphilis. The incidence here was 31.03%, slightly lower than the 35% reported by Dawson-Butterworth and Heathcote. The other clinical signs, such as tendon hyperreflexia, positive Babinski's sign, cerebellar ataxia, paresthesia, and optic atropy, were similar to those reported in recent literature.15,16,18

Results of EEG in most patients showed generic arrhythmic slow activity. Moderate or worse abnormal EEG activity and severe asymmetrical brain electrical activity were also detected. They are not specific, however, and can also be seen in other diseases. Anghinah et al.19 reported two GP cases characterized by progressive cognitive impairment followed by partial complex seizures, for which the EEG showed generalized periodic activity like those appearing in Creutzfeldt-Jakob disease. Our data revealed single epileptiform discharge in five patients, yet no generalized periodic activity.

Neuroimaging of neurosyphilis generally is not very specific and thus is of limited value in making a diagnosis. Our MRI/CT finding in patients (Figure 1) was mainly focal atrophy in one or multiple cerebral regions, especially in the frontal and temporal lobes, seldom in the occipital lobe and cerebellum, which was consistent with others' reports.20 Kodama et al.21 has suggested that MRI could be of prognostic value in patients with general paresis. They described severe atrophy, especially in the medial temporal lobe, which may be a poor prognostic sign in GP. For the purpose of verification, we may follow up these cases in a further study to observe their prognostic values. Single or multiple spotty or patchy lesions, mainly located in the cerebral cortex, subcortical white matter, and basal ganglia, with long T-1 and T-2 signal, were observed in 84.48% (98 patients). They were considered the result of insufficient blood to the brain caused by syphilitic cerebral vasculitis. Good and Jäger22 reported diffusely enhancing meninges around the brain and spinal cord, and pointed out there might exist obstruction of the CSF. Our study found that more than 20% of patients suffered thickened cerebral dura mater and hydrocephalus. Cognitive deterioration, ataxia, and incontinence of feces and urine were the most common clinical manifestation in these cases.

 
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FIGURE 1.Typical Changes on MRI

Note the brain atrophy involving bilateral frontal and temporal lobes, with enlargement of bilateral ventricles. Multiple spotty or patchy lesions can be seen in the subcortical white matter, with long T-1 and T-2 signal intensity, and can be more easily seen on FLAIR MRI.

As for syphilis pathogenic examination, positive blood TPHA and TRUST tests were seen in 100% of patients. For CSF samples, the positive rate of TPHA was 100%, whereas TRUST was 86.21%; statistical analysis indicated that TRUST was less sensitive than TPHA for CSF samples (p<0.05). There were also reports of negative TRUST values in the CSF of GP patients,23,24 coinciding with our interpretation of the question.

GP has diverse clinical manifestations and can easily be misdiagnosed as schizophrenia, depression, and viral encephalitis. In elderly patients, it is especially likely to be misdiagnosed as vascular dementia. Our data showed that the rate of misdiagnosis was 36.21%, and the mean duration for the misdiagnosis lasted from 1 month to 24 months (mean: 8.2 [SD: 4.6] months). A similar finding has also been reported by others.25,26

GP is considered to be a treatable dementia; however, its early diagnosis and treatment play a very important role. The clinical presentation of GP varies considerably among patients. For those with progressive cognitive and behavioral deterioration accompanied by psychotic and/or affective disorders or cerebral atrophy of unknown cause, general paresis should be considered.

Authors Dong Zheng and Daoyou Zhou contributed equally to this work.

This study was supported by a grant to Jun Liu from the National Natural Science Fundation of China (No. 30970966).

Chen  XS;  Gong  XD;  Liang  GJ  et al:  Epidemiologic trends of sexually transmitted diseases in China.  Sex Transm Dis 2000; 27:138–142
[PubMed]
[CrossRef]
 
Podwinska  J:  Syphilis and AIDS.  Arch Immunol Ther Exp (Warsz) 1996; 44:329–333
[PubMed]
 
Chesson  HW;  James  D;  Voigt  RF  et al:  Estimates of primary and secondary syphilis rates in persons with HIV in the United States, Sexually Transmitted Diseases, 2002.  Sex Transm Dis 2005; 32:265–269
[PubMed]
[CrossRef]
 
San Francisco Department of Public Health:  San Francisco Sexually Transmitted Disease Annual Report, 2004; available at http://www.dph.sf.ca.us/reports/std/ sfstdannlsum2004.pdf
 
Marra  CM:  Syphilis and human immunodeficiency virus: prevention and politics.  Arch Neurol 2004; 61:1505–1508
[PubMed]
[CrossRef]
 
Hook  EW  3rd;  Peeling  RW:  Syphilis control: a continuing challenge.  N Engl J Med 2004; 351:122–124
[PubMed]
[CrossRef]
 
Chen  ZQ;  Zhang  GC;  Gong  XD  et al:  Syphilis in China: results of a national surveillance programme.  Lancet 2007; 369:132–138
[PubMed]
[CrossRef]
 
Jay  CA:  Treatment of neurosyphilis.  Curr Treat Options Neurol 2006; 8:185–192
[PubMed]
[CrossRef]
 
Wardropper  AG;  Snow  M:  Neurosyphilis and HIV infection.  Int J STD AIDS 1994; 5:146–148
[PubMed]
 
Teixeira  AL;  Malheiros  JA;  Lambertucci  JR:  Rapid progressive dementia associated with neurosyphilis.  Rev Soc Bras Med Trop 2006; 39:390–391
[PubMed]
[CrossRef]
 
Kohler  CG;  Pickholtz  J;  Ballas  C:  Neurosyphilis presenting as schizophrenia-like psychosis.  Neuropsychiatry Neuropsychol Behav Neurol 2000; 13:297–302
[PubMed]
 
Liu  MC:  General paresis of the insane in Peking between 1933 and 1943.  J Ment Sci 1960; 106:1082–1092
[PubMed]
 
Cohen  MS;  Hawkes  S;  Mabey  D:  Syphilis returns to China with a vengeance.  Sex Transm Dis 2006; 33:724–725
[PubMed]
[CrossRef]
 
Lindsay  MK;  Adefris  W;  Willis  S  et al:  The risk of sexually transmitted diseases in human immunodeficiency virus-infected parturients.  Am J Obstet Gynecol 1993; 169:1031–1035
[PubMed]
 
Dawson-Butterworth  K;  Heathcote  PR:  Review of hospitalized cases of general paresis of the insane.  Br J Vener Dis 1970; 46:295–302
[PubMed]
 
Dewhurst  K:  The neurosyphilitic psychoses today: a survey of 91 cases.  Br J Psychiatry 1969; 115:31–38
[PubMed]
[CrossRef]
 
Chia  BH;  Tsoi  WF:  A study of 136 cases of general paralysis of the insane (dementia paralytica) in a mental hospital.  Singapore Med J 1971; 12:264–270
[PubMed]
 
Nordenbo  AM;  Sørensen  PS:  The incidence and clinical presentation of neurosyphilis in greater Copenhagen, 1974 through 1978.  Acta Neurol Scand 1981; 63:237–246
[PubMed]
[CrossRef]
 
Anghinah  R;  Camargo  EC;  Braga  NI  et al:  Generalized periodic EEG activity in two cases of neurosyphilis.  Arq Neuropsiquiatr 2006; 64:122–124
[PubMed]
[CrossRef]
 
Berbel-Garcia  A;  Porta-Etessam  J;  Martinez-Salio  A  et al:  Magnetic resonance image-reversible findings in a patient with general paresis.  Sex Transm Dis 2004; 31:350–352
[PubMed]
[CrossRef]
 
Kodama  K;  Okada  S;  Komatsu  N  et al:  Relationship between MRI findings and prognosis for patients with general paresis.  J Neuropsychiatry Clin Neurosci 2000; 12:246–250
[PubMed]
[CrossRef]
 
Good  CD;  Jäger  HR:  Contrast enhancement of the cerebrospinal fluid on MRI in two cases of spirochetal meningitis.  Neuroradiology 2000; 42:448–450
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Lessig  S;  Tecoma  E:  Perils of the prozone reaction: neurosyphilis presenting as an RPR-negative subacute dementia.  Neurology 2006; 66:777
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Lee  JW;  Wilck  M;  Venna  N:  Dementia due to neurosyphilis with persistently negative CSF VDRL.  Neurology 2005; 65:1838
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[CrossRef]
 
Rothschild  BM;  Behnam  S:  The often overlooked digital tuft: clues to diagnosis and pathophysiology of neuropathic disease and spondyloarthropathy.  Ann Rheum Dis 2005; 64:286–290
[PubMed]
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Barrett  AM:  Is it Alzheimer's disease or something else? 10 disorders that may feature impaired memory and cognition.  Postgrad Med 2005; 117:47–53
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References Container

FIGURE 1. Typical Changes on MRI

Note the brain atrophy involving bilateral frontal and temporal lobes, with enlargement of bilateral ventricles. Multiple spotty or patchy lesions can be seen in the subcortical white matter, with long T-1 and T-2 signal intensity, and can be more easily seen on FLAIR MRI.

+

References

Chen  XS;  Gong  XD;  Liang  GJ  et al:  Epidemiologic trends of sexually transmitted diseases in China.  Sex Transm Dis 2000; 27:138–142
[PubMed]
[CrossRef]
 
Podwinska  J:  Syphilis and AIDS.  Arch Immunol Ther Exp (Warsz) 1996; 44:329–333
[PubMed]
 
Chesson  HW;  James  D;  Voigt  RF  et al:  Estimates of primary and secondary syphilis rates in persons with HIV in the United States, Sexually Transmitted Diseases, 2002.  Sex Transm Dis 2005; 32:265–269
[PubMed]
[CrossRef]
 
San Francisco Department of Public Health:  San Francisco Sexually Transmitted Disease Annual Report, 2004; available at http://www.dph.sf.ca.us/reports/std/ sfstdannlsum2004.pdf
 
Marra  CM:  Syphilis and human immunodeficiency virus: prevention and politics.  Arch Neurol 2004; 61:1505–1508
[PubMed]
[CrossRef]
 
Hook  EW  3rd;  Peeling  RW:  Syphilis control: a continuing challenge.  N Engl J Med 2004; 351:122–124
[PubMed]
[CrossRef]
 
Chen  ZQ;  Zhang  GC;  Gong  XD  et al:  Syphilis in China: results of a national surveillance programme.  Lancet 2007; 369:132–138
[PubMed]
[CrossRef]
 
Jay  CA:  Treatment of neurosyphilis.  Curr Treat Options Neurol 2006; 8:185–192
[PubMed]
[CrossRef]
 
Wardropper  AG;  Snow  M:  Neurosyphilis and HIV infection.  Int J STD AIDS 1994; 5:146–148
[PubMed]
 
Teixeira  AL;  Malheiros  JA;  Lambertucci  JR:  Rapid progressive dementia associated with neurosyphilis.  Rev Soc Bras Med Trop 2006; 39:390–391
[PubMed]
[CrossRef]
 
Kohler  CG;  Pickholtz  J;  Ballas  C:  Neurosyphilis presenting as schizophrenia-like psychosis.  Neuropsychiatry Neuropsychol Behav Neurol 2000; 13:297–302
[PubMed]
 
Liu  MC:  General paresis of the insane in Peking between 1933 and 1943.  J Ment Sci 1960; 106:1082–1092
[PubMed]
 
Cohen  MS;  Hawkes  S;  Mabey  D:  Syphilis returns to China with a vengeance.  Sex Transm Dis 2006; 33:724–725
[PubMed]
[CrossRef]
 
Lindsay  MK;  Adefris  W;  Willis  S  et al:  The risk of sexually transmitted diseases in human immunodeficiency virus-infected parturients.  Am J Obstet Gynecol 1993; 169:1031–1035
[PubMed]
 
Dawson-Butterworth  K;  Heathcote  PR:  Review of hospitalized cases of general paresis of the insane.  Br J Vener Dis 1970; 46:295–302
[PubMed]
 
Dewhurst  K:  The neurosyphilitic psychoses today: a survey of 91 cases.  Br J Psychiatry 1969; 115:31–38
[PubMed]
[CrossRef]
 
Chia  BH;  Tsoi  WF:  A study of 136 cases of general paralysis of the insane (dementia paralytica) in a mental hospital.  Singapore Med J 1971; 12:264–270
[PubMed]
 
Nordenbo  AM;  Sørensen  PS:  The incidence and clinical presentation of neurosyphilis in greater Copenhagen, 1974 through 1978.  Acta Neurol Scand 1981; 63:237–246
[PubMed]
[CrossRef]
 
Anghinah  R;  Camargo  EC;  Braga  NI  et al:  Generalized periodic EEG activity in two cases of neurosyphilis.  Arq Neuropsiquiatr 2006; 64:122–124
[PubMed]
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