On one occasion, he bought a weekly train ticket on consecutive days. He also had lost ... Email: somervil @medeserv.com.au forget ....â He scored 9 of 30 in the ...
L p k p i u , 40(9):1309-131 I , 1999 Lippincott Williams & Wilkina, Inc., Philadelphia 0 International League Against Epilepsy
Brief Communication
Intractable Epilepsy as the Initial Manifestation of Neurosyphilis Thanh G. Phan, Ernest R. Somerville, and *Sharon Chen Departments qf Neurology and *Infectious Diseases, Westmead Hospital, Sydney, NSW, Australia
Summary: A 29-year-old man experienced intractable partial
Syphilis should be considered in patients with adult-onset focal epilepsy, particularly if there is associated dementia. Treatment may be successful even when the diagnosis is delayed. Key Words: Seizure-Dementia-Neurosyphilis-Therapy.
seizures as the initial manifestation of neurosyphilis. The diagnosis was made after the onset of dementia 9 months later. Both the epilepsy and dementia resolved with penicillin therapy. -
forget ....” He scored 9 of 30 in the Mini-Mental State examination. There were no frontal release signs. The pupils were 4 mm in size and reacted equally and consensually to light; accommodation was normal. Tone, power, and all reflexes were normal. Sensory examination was normal to touch, pin-prick, vibration, and jointposition sense. The rest of the physical examination was normal. Routine hematology, erythrocyte sedimentation rate, biochemistry, thyroid-function tests, serum B ,2, and folate were normal. Anti-nuclear antibody and antineutrophil cytoplasmic antibody were not detected. Magnetic resonance imaging (MRI) of the brain was normal. Brain HMPAO single-photon emission computed tomography (SPECT) scan revealed mild right frontal hypoperfusion. EEG after the first seizure was normal, but 18 months later, revealed diffuse slow waves and frontal intermittent rhythmic delta activity (Fig. 1A). A smallbowel biopsy was normal. Antibodies to human immunodeficiency virus were not detected. Serum VDRL was positive (titer, 1:8); serum TPHA and FTA-ABS were reactive. Cerebrospinal fluid (CSF) examination showed a mononuclear pleocytosis and reactive VDRL (titer, 1:2). He was treated with intravenous penicillin G, 18 million units, and prednisone, 50 mg daily for 18 days. By day 10 of therapy, there was considerable improvement in memory, verbal fluency, and the ability to perform sequential tasks. As his memory recovered, he recalled having a lesion on the penis 10 years previously, which had been treated with a cream. An EEG 3 weeks later was normal (Fig. 1B). Antiepileptic medication was ceased after 12 months. Twenty months after cessation of therapy, there have
Neurosyphilis is a well-recognized cause of acute symptomatic seizures ( 1 4 ) . However, it is rarely considered as an etiologic possibility in chronic intractable epilepsy. We describe a patient with intractable partial epilepsy in whom the diagnosis of neurosyphilis was not suspected until the onset of dementia.
CASE REPORT A 29-year-old man had his first seizure 18 months before presentation. There was clenching of the right fist, followed by secondary generalization. The second seizure occurred 3 months later, and carbamazepine (CBZ) was introduced. Despite the addition of gabapentin (GBP) and lamotrigine (LTG) seizures continued. Beginning 9 months after the first seizure, his wife noted a gradual change in his personality. He no longer groomed himself and was unable to follow conversations. On one occasion, he bought a weekly train ticket on consecutive days. He also had lost interest in sex and was unable to achieve a full erection. As a result of continuing poor performance at work as a laborer, his employment was terminated 3 weeks before admission. He was orientated in person and place but not in time. He was unable to perform simple calculations and could not register three verbal items. Repetition was poor, and verbal fluency was reduced. He could not explain the nature of his job, and when asked what his problems were, he stated “I forget...I Accepted February 16, 1999. Address correspondence and reprint requests and reprint requests to Dr. E.R. Somerville at 113 Hawkesbury Rd., Westmead 2145, NSW, Australia. Email: somervil @medeserv.com.au
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T. C. PHAN ET AL.
1310 A
FPZ-CZ FCCZ CCCZ PCCZ 02-cz FP1-CZ F3-CZ c3-cz P3-cz 01-cz Fa-CZ TQCZ TCCZ F7-CZ T3-CZ TI-CZ ECG
+ FIG. 1. EEG before treatment showing generalised slowing (A) and 3 weeks after commencement of antibiotic therapy, showing normal background (B).
been no further seizures. He returned to work 1 month after discharge and has been promoted to factory supervisor.
DISCUSSION Neurosyphilis is now uncommon. Delay in the diagnosis of our patient was due to the initial absence of a history of early syphilis and the absence of pupillary or reflex abnormalities. A history of a primary lesion is present in 56% of cases of syphilitic meningitis, and a history of a rash, in 40% (4). However, in a patient with dementia, it may not be possible to elicit such a history. Syphilitic seizures were present in this patient long before dementia became apparent. This was not unusual in the preantibiotic era. Syphilitic seizures are commonest among patients with syphilitic meningitis and cerebrovascular syphilis, with a prevalence of -15%. They occur late in the course of general paralysis of the insane (GPI) (1,2). Cerebral gumma also may cause partial seizures (5). Status epilepticus has been described with neurosyphilis and may be the presenting sign (1,2,5,6). Hooshmand (4) noted that a third of his patients with syphilitic seizures were “asymptomatic.” Seizures from meningovascular syphilis have the best prognosis after antibiotic therapy, whereas seizures from GPI are more likely to persist. Younger patients with short duration of symptoms have a favorable prognosis for seizure control Epilepsia, V d . 40, No. 9, I999
(2,4). More than half of patients with meningovascular syphilis and “unclassified syphilis” become seizure free, and -30% of these patients have fewer seizures after treatment of syphilis. EEG findings are not useful in pointing to a syphilitic etiology. Spikes and sharp waves, periodic lateralized epileptiform discharges, and slowing have all been described. As in our patient at the onset of his epilepsy, 19% of patients with syphilitic seizures have a normal EEG (4). The brain MRI was unhelpful in arriving at the diagnosis. In a series of 35 patients with neurosyphilis, normal brain MRI was noted in 3 1%, cerebral infarction in 23%, nonspecific white-matter lesions in 20%, and cerebral gumma and cerebral atrophy in 37%. However, the majority of these patients had concomitant human immunodeficiency virus (HIV) infection (7). The experience with SPECT scanning in the evaluation is limited. Perfusion abnormalities can be either unilateral or bilateral; these changes can improve after treatment (8). Neurosyphilis is rare but should be excluded in patients with unexplained adult-onset epilepsy, particularly if there is also dementia. Epilepsy may be the sole presenting feature of neurosyphilis. Both the dementia and epilepsy are reversible with appropriate antibiotic therapy. Acknowledgment: Special thanks to Dr. Grant Walker, who suggested the diagnosis of neurosyphilis.
INTRACTABLE EPILEPSY AND NEUROSYPHILIS
REFERENCES 1. Merritt HH, Moore M. Acute syphilitic meningitis. Medicine 1935; 14:1 19-83. 2. Merritt HH, Adams RDA, Solomon HC. Neurosyphilis. Oxford University Press, 1946. 3. Hotson JR. Modern neurosyphilis: a partially treated chronic meningitis. Wesr J Med I98 I ; 135:191-200. 4. Hooshmand H. Seizure disorders associated with neurosyphilis. Dis Nerv Sysr 1976; 37: 133-6. 5. Suarez JI, Mlakar D, Snodgrass SM. Cerebral syphilitic gumma in
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an HIV-negative patient presenting as prolonged focal motor status epilepticus. N Engl J Med 1996; 335: 1159-60. 6, PrimaVera A, Solaro C, Cocito L. De nova epilepticus as the presenting sign of neurosyphilis. Epilepsiu 1998;39:1367-9. 7. Brightbill TC, Ihmeidan IH, Donovan J, Post M, Joseph R, Katz B, Katz D. Neurosyphilis in HIV-positive and HIV-negative patients: neuroimaging findings. AJNR 1995;16:703-11. 8. Kawai N, Baba A, Mizukami K, Sakai T, Shiraishi H, Kizumi J. CT, MR and SPECT findings in general paresis. Comput Med Imaging Gruph I 994; 18:46 1-5.
EptlepJia, Vol. 40, No. 9. 1999
