Hakim-Adams syndrome secondary to syphilis

doi:10.4236/crcm.2013.26101

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Vol.2, No.6, 377-379 (2013) Case Reports in Clinical Medicine

http://dx.doi.org/10.4236/crcm.2013.26101

Hakim-Adams syndrome secondary to syphilis

Ricardo Krause Martinez de Souza1, Alexandre Zatera2, Fernanda Leal Suzano2*,

Flávia de Oliveira Braga2, Samanta Fabrício Blattes da Rocha2, Ricardo Ramina3,

Pedro André Kowacs2

1Ambulatório de Desordens da Memória e do Comportamento, Instituto de Neurologia de Curitiba, Curitiba, Brazil

2Instituto de Psiquiatria do Paraná, Curitiba, Brazil; *Corresponding Author: [email protected]

3Serviço de Neurologia e Neurocirurgia, Curitiba, Brazil

Received 8 May 2013; revised 12 June 2013; accepted 8 July 2013

Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is

properly cited.

ABSTRACT

Normal pressure hydrocephalus (NPH) second-

ary to syphilis is an atypical form of neuro-

syphilis with an unusual clinical presentation

and uncommon neuroimaging findings. A case

of Syndrome de Hakim- Adams occurr ing in a 79-

year-old male was admitted for investigation of a

dementia syndrome. The patient presented with

clinical features and neuroimaging compatible

with NPH. Syphilis serology was reactive and

compatible with active disease. The patient was

treated with crystalline p enicillin (4 million units

every 4 hours for 21 days) and was assessed

again after three months, when his cognition

and gait had improved and the urinary inconti-

nence had resolved. According to this infor-

mation, we describe a case of syphilis mimick-

ing normal pressure hydrocephalus, making clear

the importance of the investigation of sexually

transmitted diseases in the differential diagno-

sis of dementia, even in patients without estab-

lished risk supposedly.

Keywords: Neurosyphilis; Hakim-Adam s Syndrome;

Syphilis; Normal Pressure Hydrocephalus

1. INTRODUCTION

Syphilis is a sexually transmitted disease caused by

the spirochete Treponema pallidum (T. pallidum), which

causes neurosyphilis when it invades the nervous system.

The initial neurological manifestations of neurosyphilis

are asymptomatic meningitis, acute syphilitic meningitis

and meningovascular syphilis. In the late stages of the

disease, there may be involvement of the spinal cord and

cerebral cortex, causing tabesdorsalis or general paresis,

which is also known as paralytic dementia [1]. Other

presentations of neurosyphilis have been described, such

as limbic encephalitis [2] and normal pressure hydro-

cephalus [3], which are referred to as atypical forms of

neurosyphilis.

The aim of this paper is to describe a case of atypical

neurosyphilis mimicking NPH in which treatment with

crystalline penicillin resulted in a considerable improve-

ment in symptoms.

2. CASE REPORT

A 79-year-old male was admitted to the Curitiba In-

stitute of Neurology for investigation of a dementia syn-

drome. The patient presented with symptoms marked by

gait apraxia, dementia and urinary incontinence that had

been worsening progressively over 1.5 years. On admis-

sion he was taking donepezil 5 mg. In the previous six

months his symptoms had worsened, leading him to seek

a second opinion. Laboratory tests were carried out and

the patient had a brain MRI scan, lumbar puncture and

neuropsychological assessment.

HIV serology was nonreactive and vitamin B12, folic

acid and TSH levels were normal. Syphilis serology was

reactive and compatible with active disease (second line

of the Table 1).

Cerebrospinal fluid (CSF) analysis revealed an in-

crease in protein concentration (72 mg/dL) any cellular

alterations. Opening pressure was 12 cm H2O, and VDRL

(venereal disease research laboratory) and FTA-ABS

(fluorescent treponemal antibody-absorption) tests were

nonreactive.

The MRI revealed ventricular dilation (Evans’ index

of 0.31) out of proportion to the degree of atrophy (Fig-

ure 1). Neuropsychological assessment showed cogni-

tive alterations associated with frontal-subcortical dys-

function, confirming the diagnosis of dementia.

R. K. M. de Souza et al. / Case Reports in Clinical Medicine 2 (2013) 377-379

378

Table 1. Serological profile of syphilis (total antibodies).

CMIA/EIA RPR TPHA/TP-PA

Non-reactivesyphilis −

Active syphilis + +

Treatedorlatentsyphilis + − +

Recent primary syphilis or

false positive + − −

CMIA/EIA: chemiluminescent microparticle immunoassay/syphilis enzyme

immunoassay; RPR: rapid plasma reagin; TPHA/TP-PA: Treponema palli-

dum hemagglutination assay/Tre ponema pallidum particle agglutination assay.

Figure 1. Brain MRI scan. (A) Axial FLAIR (Fluid At-

tenuated Inversion Recovery) sequence showing dilation

of the ventricular system out of proportion to the degree

of cerebral atrophy, and rounding of the frontal and oc-

cipital horns (arrows); (B) Coronal T2-weighted sequence

showing a callosal angle of 90˚, dilation of the temporal

horns (arrows) and tight high-convexity and medial sur-

face subarachnoid spaces (dotted arrows).

The patient was treated with crystalline penicillin (4

million units every 4 hours for 21 days) and was assessed

again after three months, when his cognition and gait had

improved and the urinary incontinence had resolved. A

NPH scale [8] was used to measure the clinical improve-

ment.

3. DISCUSSION

When syphilis is suspected, both treponemal (FTA-

ABS, TP-PA and EIA) and non-treponemal (VDRL and

RPR) tests should be carried out [1]. When the VDRL

test in CSF is reactive, a diagnosis of neurosyphilis can

be made. However, a nonreactive VDRL test does not

exclude a diagnosis of neurosyphilis. FTA-ABS in CSF

is sensitive but is not specific. However, if it is not reac-

tive, a diagnosis of neurosyphilis can usually be excluded

[1]. Our patient’s serum was reactive in CMIA and RPR

tests, indicating active syphilis (Table 1); his CSF find-

ings included elevated protein levels and a nonreactive

FTA-ABS test. There have been reports of rare cases in

which serologic tests for syphilis in CSF have been non-

reactive [1].

NPH secondary to syphilis is an atypical form of neu-

rosyphilis with an unusual clinical presentation [3] and

uncommon neuroimaging findings [4]. Pedersen et al.,

1979, described a case of NPH secondary to syphilis that

improved significantly with antibiotics [3]. A diagnosis

of NPH is made when its triad of signs and symptoms

(gait apraxia, dementia and urinary incontinence) is pre-

sent together with an opening CSF pressure of less than

18 cm H2O and ventricular dilation that cannot be attrib-

uted exclusively to cerebral atrophy. The neuroimaging

characteristics observed in our case, which included a

callosal angle of approximately 90˚ [6], tight high-con-

vexity and medial surface subarachnoid spaces [7] and

rounding of the frontal and temporal horns, support a

diagnosis of NPH. The patient’s NPH score [8] was the

parameter used to classify the response to treatment. The

NPH scale assesses three domains (gait, cognition and

sphincter control), with scores of between 1 and 5 for

each item. The total score can vary from a minimum of 3

points (patient completely incapacitated) to a maximum

of 15 (total independence). The result for our patient was

9/15 before treatment and 13/15 after treatment. There

was an improvement of 1 point in gait and cognition and

2 points in sphincter control. The overall improvement of

4 points was considered significant.

The patient presented with the classic Hakim-Adams

triad, with neuroimaging compatible with NPH. The

finding of normal opening pressure excluded the possi-

bility of hypertensive hydrocephalus. In view of the risks

associated with ventriculoperitoneal shunt surgery in an

elderly patient and the presence of active syphilis in the

blood, we decided to administer empirical treatment for

R. K. M. de Souza et al. / Case Reports in Clinical Medicine 2 (2013) 377-379

379

neurosyphilis using penicillin. The improvement in the

NPH score [8] observed after administration of the anti-

biotic corroborated the diagnosis of atypical neurosyphi-

lis.

OPEN A CCESS

4. CONCLUSION

Our case illustrates an atypical form of neurosyphilis

(Hakim-Adams syndrome), which is considered in the

literature to be a rare yet an important manifestation of

this disease as it involves potentially reversible dementia.

The absence of positive serology for syphilis in the CSF

should not exclude a diagnosis of neurosyphilis in cases

in which the clinical findings are suggestive of this in-

fection. Physicians should bear in mind that tests can

yield false-negative results and should trust their clinical

impressions when these are relevant to the patient’s

treatment.

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