Secondary Logo

A Case Report of Neurosyphilis Limbic Encephalitis With Reversible Geschwind Syndrome and Mood Disorder

TOFFANIN, TOMMASO, MD, PhD; MIOLA, ALESSANDRO, MD; FOLLADOR, HALIMA, MD, PhD; FERRI, GIOVANNI, MD, PhD; SCUPOLA, NADIA, PhD; MARTINO, NICOLA, MD; BARATTO, ALESSANDRA, MD; PERINI, GIULIA IDA, MD

Journal of Psychiatric Practice®: May 2019 - Volume 25 - Issue 3 - p 222–226
doi: 10.1097/PRA.0000000000000390
Clinical Case Discussions
Free

Limbic encephalitis is an inflammatory process of the limbic structures, with polymorphic clinical features, caused by paraneoplastic and nonparaneoplastic conditions and infections. We describe a case of neurosyphilis limbic encephalitis, presenting with reversible Geschwind syndrome (hyperreligiosity and hypergraphia) and mood disorder due to the predominant involvement of left mesial temporal structures in a previously healthy 34-year-old, left-handed woman. Because neurosyphilis can mimic common neuropsychiatric syndromes, it should be included in the differential diagnosis of psychiatric disorders with suspected general medical causes. This case of nondominant limbic encephalopathy caused by syphilis infection highlights the relevance of a careful investigation for secondary psychotic, mood, and personality disorders when assessing new-onset psychiatric illness and the importance of a multidisciplinary approach to provide a better outcome in patients with neurosyphilis.

TOFFANIN, MIOLA: Department of Neurosciences, Section of Psychiatry, University-Hospital of Padova, Padova, Italy

FOLLADOR: Department of Psychiatry, Hospital of Conegliano, ULSS 2, Treviso, Italy

FERRI: Department of Psychiatry, Hospital of Cittadella, ULSS 6, Padova, Italy

SCUPOLA: Casa di Cura Parco dei Tigli, Teolo, Padova, Italy

MARTINO and BARATTO: Unit of Radiology, Hospital of Conegliano, ULSS 2, Treviso, Italy

PERINI: Department of Neurosciences, University of Padova, and Casa di Cura Parco dei Tigli, Teolo, Padova, Italy

The authors declare no conflicts of interest.

Please send correspondence to: Tommaso Toffanin, MD, PhD, Department of Neurosciences, Section of Psychiatry, University-Hospital of Padova, Via Giustiniani 2, 35128 Padova, Italy (e-mail: tommaso.toffanin@aopd.veneto.it).

Limbic encephalitis (LE) refers to an inflammatory process that involves the limbic system. It may occur in paraneoplastic and nonparaneoplastic conditions and in infectious subtypes. The classical syndrome of LE manifests itself with confusional states, mood disturbances, hallucinations, anterograde amnesia, and partial or less commonly generalized seizures, and it has a rapidly progressive course.1,2 However, due to its polymorphic clinical features, an early diagnosis is often missed, and the clinical picture is often underdiagnosed or misdiagnosed.3

In this report, we describe the case of a woman with neurosyphilis encephalitis. At the very onset of the disease, she displayed pseudo-depressive symptoms; she later developed a manic state and then started displaying an unequivocal “temporal lobe” personality profile, indicative of limbic system involvement, such as hyperreligiosity, interest in philosophical themes, and quite extensive hypergraphia. Geschwind syndrome in temporal lobe epilepsy (TLE) with characteristic interictal personality changes was described by Waxman and Geschwind4 in 1975 and by Blumer and Benson in 1982.5 However, even if the characteristic triad of personality changes involving hyperreligiosity, hypergraphia, and hyposexuality are unique to focal TLE epilepsy compared with other types of epilepsy,6,7 other conditions involving the medial temporal lobe and limbic structures, such as frontotemporal degeneration, may also display this unique profile of personality and behavioral changes.8,9

Back to Top | Article Outline

CASE PRESENTATION

A previously healthy 34-year-old, left-handed woman was first hospitalized on the psychiatric unit at the Hospital of Conegliano (Treviso, Italy) in November 2010 with a 6-month history of psychiatric disturbances such as low mood, anxiety, delusions of guilt and of poverty, paranoid ideation, psychomotor retardation, blunted affect and poverty of thought, derealisation, insomnia, and significant impairment in social and occupational areas. The patient had no history of alcohol abuse or use of illicit drugs, nor did she have any previous personal or family history of mental illness. General physical and neurological examinations revealed otherwise unremarkable findings. Routine blood examination did not show any abnormality. The patient was treated with olanzapine (20 mg/d), and diazepam (8 mg/d) with partial response during this initial hospitalization in 2010, but she reported that she had discontinued olanzapine and diazepam a few weeks after she was discharged from the hospital in December 2010 and returned to living in Ukraine with her parents. At that time, she continued to experience symptoms of depression and social withdrawal.

In September 2011, the patient was rehospitalized after 3 months of hypomanic symptoms, flight of ideas, spiritual and religious delusions, insomnia, auditory hallucinations, kleptomania-like behavior, and hypergraphia with partial insight. Her score on the 24-item Brief Psychiatric Rating Scale (BPRS-24) was 94 (indicating that she was extremely ill). After her admission, the patient started spending almost all day in the hospital occupational therapy room, copying pages and pages from books into her diary. In the meanwhile, a left ansicoria that was not reactive to light was detected on neurological examination. An electroencephalogram showed slowing over the left temporal lobe. When magnetic resonance imaging (MRI) of the patient’s brain was done, a fluid-attenuated inversion recovery (FLAIR) acquisition revealed cortical thickening of the inferior and mesial temporal cortex on the left side, which was associated with hyperintensities and edema of the surrounding white matter; the entire left hippocampus was also involved. Milder hyperintensities were also present in the ipsilateral insular cortex and frontal pole, and, to a lesser extent, in the contralateral insular cortex and hippocampal head. No restrictions of the diffusion coefficient or focal enhancement abnormalities were found (Figs. 1A, B).

FIGURE 1

FIGURE 1

The patient’s psychiatric symptoms were managed with olanzapine (10 mg/d), divalproex sodium (1000 mg/d), and diazepam (6 mg/d). A differential diagnosis workup for LE was started. The results of routine laboratory tests were normal. The patient was serologically negative for human immunodeficiency virus infection, hepatitis C virus, and borrelia burgdorferi, but her results were positive for syphilis [Venereal Disease Research Laboratory (VDRL) titer of 1:8 and Treponema pallidum hemagglutination assay (TPHA) titer of 1:10240]. Autoantibodies to Ri, Yo, Amphiphysin, CV2, and PNMA2 (Ma2/Ta) were negative. Cerebrospinal fluid (CSF) showed protein 1.41 g/L (normal value, 0.2 to 0.4 g/L), white blood cells 48/mm3 (normal value<2/mm3), Ig G 0.712 g/L (normal value, 0.008 to 0.0420), oligoclonal bands, lymphocytic pleocytosis, and no malignant cells. Polymerase chain reactions for CMV-DNA, HSV1-DNA, HSV2-DNA, VZV DNA, and Enterovirus-RNA were negative. Her CSF was reactive for TPHA, at a titer of 1:81920.

On neuropsychological assessment, the patient showed significant impairment in many different cognitive domains (attention, memory, visual functioning, and executive function). Results of the following neuropsychological tests were abnormal: digit span forward and backward (score=4, cutoff 5); immediate and delayed recall of a short history (scores=9 and 10, cutoff 10 and 15, respectively, to first and second recall); memory with interference at 10 and 30 seconds (scores=3 and 9, cutoff 7 and 6, respectively, for first and second test); Trail-making Test parts A and B (score=56 and 188 s, cutoff 44 and 144 s, respectively); phonemic verbal fluency test (score=9, cutoff 12); cognitive estimation (score=4, cutoff 4); overlapping figures test (score=14, cutoff 36), and clock drawing test (score=4.5, cutoff 9). A diagnosis of neurosyphilis encephalitis was made, and the patient was treated with parenteral ceftriaxone (1 g daily for 14 days).

An MRI scan 4 weeks after the administration of ceftriaxone showed slow incomplete regression of the radiologic abnormalities, which were still substantially persistent, and a pronounced enlargement of the Silvane sulci indicating a worsening of already existing atrophy (Fig. 1C).

Twelve weeks after the treatment for neurosyphilis, MRI showed a reduction of the thickening of the left temporal cortex and of the left polar temporal cortex, an enlargement of the lateral ventricles’ temporal horns bilaterally (due to progressive atrophy), a residual glial sclerosis of the insula, and a mild edema (Figs. 1D, E). Neuropsychological evaluation showed only mild improvement, with the Trail-making tests A and B, digit span forward and backward, and cognitive estimation normal but no changes on immediate and delayed recall of a short history, memory with interference at 10 and 30 seconds, the phonemic verbal fluency test, the overlapping figures test, or the clock drawing test. Her psychiatric symptoms were in full remission at the time of the 12-week MRI reevaluation (score on the BPRS-24=33). At that time, the patient was well oriented to time, space, and person, and her language and psychomotor behavior were normal. The mood symptoms with spiritual and religious overvaluation and hypergraphia were in remission. No macroscopic residual alterations in the form and content of thought nor alterations of the perceptual sphere were observed. Her sleep-wake circadian rhythm had gradually returned to normal. Her insight concerning her disease and adherence to therapy were at a very good level. Psychopharmacological therapy continued throughout the entire course of treatment with olanzapine, divalproex sodium, and diazepam at the same dosages.

Back to Top | Article Outline

DISCUSSION

We have presented a case of neurosyphilis LE with reversible Geschwind syndrome (hyperreligiosity and hypergraphia) and mood disorder, with predominant involvement of left mesial temporal structures in a left-handed woman. It is suggested that hyperreligiosity and hypergraphia are typically found mainly in patients with nondominant temporal lesions both in TLE and in other conditions due to stroke, cancer, and dementia.8,10,11 Neurosyphilis can occur at any time during syphilis,12 and it has been called the “chameleon of psychiatry” and “the great imitator” because of the large number of different and nonspecific clinical and psychopathological manifestations associated with it.3,13,14 In fact, patients with neurosyphilis can present with both affective and psychotic symptoms that are indistinguishable from primary psychiatric disorders. An active inflammatory process in limbic structures, especially temporal lobes, may play a role in this phenomenon; however, reports of mesiotemporal involvement in neurosyphilis are rare.15

This case of progressive limbic encephalopathy caused by syphilis infection highlights the relevance of a careful investigation of secondary psychotic, mood, and personality disorder symptoms when assessing new-onset psychiatric illness. Specific signs of limbic involvement such as Geschwind syndrome, together with affective psychotic symptoms, indicate the need for careful neurological, brain imaging, and neuropsychological evaluations due to the high probability of a general medical cause of these specific psychiatric symptoms.6,8–11

Neurosyphilis should be included in the differential diagnosis of psychiatric disorders. Since neurosyphilis can mimic common neuropsychiatric syndromes and because of increased risk of infection in psychiatric populations, patients with clinically evident psychiatric symptoms should have blood screening for syphilis and, in the case of a positive result, a lumbar puncture should be performed.16 It is accepted that the diagnosis is confirmed by a positive CSF VDRL associated with consistent clinical evidence.17

The usual clinical pattern of neurosyphilis, in people with undiagnosed syphilis, seems to be altered by inadvertently receiving incomplete treatment while taking antibiotics for other conditions. Thus, the classic form of the illness (tabe dorsalis, general paresis, meningovascular, meningeal) is rarely seen, and it may manifest itself in other atypical clinical forms.12,18,19

Penicillin G is still the first-line treatment for neurosyphilis, but ceftriaxone 2 g intravenously once per day for 10 to 14 days or doxycycline 200 mg orally 2 times/day for 28 days may be acceptable alternatives.20

Data on the treatment of psychiatric symptoms associated with neurosyphilis are limited.12 Although there are no guidelines for managing the psychiatric manifestations of neurosyphilis, case reports suggest that haloperidol and atypical antipsychotics (risperidone, quetiapine, and olanzapine), augmented with dilvalproex sodium and in combination with appropriate antibiotic therapy, seem to have clinical benefits for psychosis in patients with neurosyphilis.21

In the case described in this article, it was important to consider 2 relevant differential diagnoses: paraneoplastic LE and herpes simplex encephalitis (HSE). Paraneoplastic LE is a paraneoplastic syndrome associated with antineural antibodies produced by tumors against intracellular antigens. These antibodies include the glutamic acid decarboxylase (GAD) antibody, the VGKC antibody, the N-methyl-D-aspartate receptor (NMDAR) antibody, AMPAR, and the γ-aminobutyric acid receptor (GABA) antibody.22,23 The classical clinical presentation is characterized by subacute cognitive deterioration, especially short-term memory loss, seizures, and psychosis, suggesting involvement of the limbic system.1

The Paraneoplastic Neurological Syndrome Euronetwork has identified 4 criteria for the diagnosis of paraneoplastic LE, all of which must be met: clinical features, involvement of the limbic system on the basis of neuroimaging and neuropathologic findings, absence of other possible pathologies of limbic dysfunction, evidence of a cancer within 5 years of the diagnosis of the neurological symptoms or development of classic symptoms of limbic dysfunction in association with paraneoplastic antibodies.1,18 The absence of paraneoplastic serological markers and exclusion of cancer support our diagnosis in the case described here.

Mesiotemporal T2-weighted hyperintensity with an asymmetrical pattern has been reported in neurosyphilis and mimics neuroimaging finding in HSE.24,25 In fact, in herpes simplex virus 1 (HSV1) encephalitis, on MRI, there is an area in the temporal lobe and often in the insula of increased signal intensity on FLAIR, DWI, and T2-weighted images. The absence of temporal lobe involvement on FLAIR and DWI 48 hours after symptom onset suggests reconsideration of the diagnosis. HSV1 encephalitis presents with a subacute progression of fever, hemicranial headache, behavioral abnormalities, focal seizure activity, and focal neurological deficits, most often difficulty with word finding.16 In this case, the diagnosis of HSE was excluded by the clinical presentation and the negativity of the serology for herpes simplex.

This case report highlights the importance of a multidisciplinary approach and interdisciplinary communication among physicians (general practitioners, psychiatrists, neurologists, neuroradiologists, and infectious disease specialists) to provide a better outcome for patients with neurosyphilis.

Back to Top | Article Outline

REFERENCES

1. Mahawish K, Teinert L, Cavanagh K, et al. Limbic encephalitis. BMJ Case Rep. 2014;2014:pii: bcr2014204591.
2. Roos KL. Encephalitis. Handb Clin Neurol. 2014;121:1377–1381.
3. Friedrich F, Geusau A, Friedrich ME, et al. Das Chamaleon der Psychiatrie-Psychiatrische Manifestations-formen der Neurosyphilis. [The chameleon of psychiatry - psychiatric manifestations of neurosyphilis.]. Psychiatr Prax. 2012;39:7–13.
4. Waxman SG, Geschwind N. The interictal behavior syndrome in temporal lobe epilepsy. Arch Gen Psychiatry. 1975;32:1580–1586.
5. Blumer D, Benson FBenson DF, Blumer D. Psychiatric manifestation of epilepsy. Psychiatric Aspects of Neurological Disease (Vol II). New York: Grune & Stratton; 1982:25–48.
6. Devinsky S. Norman Geschwind’s contribution to the understanding of behavioral changes in temporal lobe epilepsy: the February 1974 lecture. Epilepsy Behav. 2009;15:417–424.
7. Perini GI, Tosin C, Carraro C, et al. Interictal mood and personality disorders in complex partial epilepsy and juvenile myoclonic epilepsy. J Neurol Neurosurg Psychiatry. 1996;61:601–605.
8. Veronelli L, Makaretz SJ, Quimby M, et al. Geschwind syndrome in frontotemporal lobar degeneration: neuroanatomical and neuropsychological features over 9 years. Cortex. 2017;94:27–38.
9. Gainotti G. Can different mechanisms underpin the “Geschwind syndrome” in temporal lobe epilepsy and in temporal lobe variant of frontotemporal degeneration? Cortex. 2017;96:134–136.
10. Roberts JK, Robertson MM, Trimble MR. The lateralising significance of hypergraphia in temporal lobe epilepsy. J Neurol Neurosurg Psychiatry. 1982;45:131–138.
11. Chan D, Anderson V, Pijnenburg Y, et al. The clinical profile of right temporal lobe atrophy. Brain. 2009;132:1287–1298.
12. Marra CM. Neurosyphilis. Continuum (Minneap Minn). 2015;21 (6 Neuroinfectious Disease):1714–1728.
13. Zheng D, ZhouD, Zhao Z, et al. The clinical presentation and imaging manifestation of psychosis and dementia in general paresis: a retrospective study of 116 cases. J Neuropsychiatry Clin Neurosci. 2011;23:300–307.
14. Friedrich F, Aigner M, Fearns N, et al. Psychosis in neurophilis—clinical aspect and implications. Psychopathology. 2014;47:3–9.
15. Jeong YM, Hwang HY, Kim HS. MRI of neurosyphilis presenting as mesiotemporal abnormalities: a case report. Korean J Radiol. 2009;10:310–312.
16. Vedes E, Geraldo EF, Rodrigues R, et al. Neurosyphilis versus herpes encephalitis in a patient with confusion, memory loss and T2-weighted mesiotemporal hyperintesity. Case Rep Infect Dis. 2012;2012:154863.
17. Friedrich F, Geusau A, Greisenegger S, et al. Manifest psychosis in neurosyphilis. Gen Hosp Psychiatry. 2009;31:379–381.
18. Wahab S, Md Rani SA, Sharis Othman S. Neurosyphilis and psychosis. Asia Pac Psychiatry. 2013;5(suppl 1):90–94.
19. Timmermans M, Carr J. Neurosyphilis in the modern era. J Neurol Neurosurg Psychiatry. 2004;75:1727–1730.
20. Conde-Sendin MA, Hernandez-Fleta JL, Cardenes-Santana MA, et al. Neurosyphilis: forms of presentation and clinical management. Rev Neurol. 2002;35:380–386.
21. Kararizou E, Mitsonis C, Dimopoulos N, et al. Psychosis or simply a new manifestation of neurosyphilis? J Int Med Res. 2006;34:335–337.
22. Sanchez FM, Zisselman MH. Treatment of psychiatric symptoms associated with neurosyphilis. Psychosomatics. 2007;23:274–277.
23. Zhang H, Zhou C, Wu L, et al. Are onconeural antibodies a clinical phenomenology in paraneoplastic limbic encephalitis? Mediators Inflamm. 2013;2013:172986.
24. Graus F, Delattre JY, Antoine JC, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry. 2004;75:1135–1140.
25. Lauria G, Erbetta A, Pareyson D, et al. Parenchymatous neurosyphilis. Neurol Sci. 2001;22:281–282.
Keywords:

Geschwind syndrome; limbic encephalitis; neurosyphilis

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.