LETTER TO THE EDITOR

Pitfalls in the diagnosis of Neuro-Behcet presentingwith psychiatric symptoms at onset: a case report!

Rocco Salvatore Calabro • Rosario Grugno •

Nunzio Muscara • Placido Bramanti

Received: 12 October 2012 / Accepted: 9 January 2013

� Springer-Verlag Italia 2013

Keywords Neuro-psycho-Behcet � Somatoform

disorders � Limbic system

Dear Sir,

Behcet’s Disease (BD) is a multi-system, vascular-inflam-

matory disease of unknown origin, characterized by

recurrent oral and genital ulcerations and uveitis with

hypopyon, and involving the nervous system in a subgroup

of patients. The majority of Neuro-Behcet’s (NBD) cases

can be characterized as a vascular-inflammatory central

nervous system (CNS) disease, which commonly presents

with the onset of a subacute brainstem syndrome, unilateral

or bilateral cortico-spinal tract signs, cerebellar findings

and mild confusion with or without disturbance in con-

sciousness [1]. Nevertheless, hemiparesis, cognitive,

behavioural and emotional disturbances, extrapyramidal

signs and seizures may be observed. However, neuropsy-

chiatric symptoms at onset are very rare, often leading to

misdiagnosis.

An otherwise healthy 31-year-old woman had behav-

ioural disturbances, excessive anxiety, weakness, and loss

of appetite with some episode of visual and auditory hal-

lucinations for about 3 months. Physical and neurological

examination, as well as EEG and brain CT were normal.

The severity of psychotic symptoms was assessed using the

Brief Psychiatric Rating Scale (BPRS). As somatoform

disorder was diagnosed, venlafaxine (75 mg/day) and

amisulpiride (50 mg/day) prescribed. Although psychiatric

symptoms ameliorated (BPRS score from 56 to 26) within

3 weeks, the patient, after around 2 months of treatment,

showed upper limb weakness and paresthesias, and thus

underwent a more specific evaluation. General examina-

tion, including ophthalmological exam, was normal while

neurological examination showed a mild hemiparesis. MR

flair images showed hyperintensities in the right amygdala

(see Fig. 1) and cingulate anterior gyrus and the left pos-

terior limb of the internal capsule. Laboratory tests,

including common autoantibodies (i.e. lupus anticoagulant,

anticardiolipin and antiphosphatidylserine antibodies,

antibeta 2 glycoprotein I, anti-nuclear, anti-smooth muscle

and anti-neutrophil cytoplasm antibodies, extractable

nuclear antigens), VES, PCR and coagulation (i.e. anti-

thrombin III, protein S and C), urinalyses and cerebrospinal

fluid examination did not reveal any abnormalities.

Since the most common alternative causes of such brain

parenchymal lesion have been ruled out (i.e. CNS infec-

tions with regards to tubercolosis, syphilis and Lyme bor-

reliosis, sarcoidosis, systemic and brain immune disorders,

including the anti-NMDA receptor Encephalitis) and

pathergy test was positive, NBD was suspected (although

the B51 HLA genotype was not detected) and the patient

treated with colchicine (1 mg/day) and antiplatelets (aspi-

rin 100 mg/day). No other brain MRI lesions were identi-

fied at 2-year follow-up.

However, during the follow-up period the patient pre-

sented with recurrent genital ulcerations, further confirm-

ing our hypothesis.

Because neurological involvement usually occurs

1–10 years after the first symptom of BD and because the

first symptom of BD is neurological/psychiatric in only

3 % of cases, NBD is sometimes very difficult to diagnose

[2]. Indeed, our patient has been misdiagnosed as affected

by somatoform disorder since, at the onset of the disease,

she presented with unspecific psychiatric symptoms and

R. S. Calabro (&) � R. Grugno � N. Muscara � P. Bramanti

IRCCS Centro Neurolesi ‘‘Bonino-Pulejo’’, S.S. 113,

Contrada Casazza, 98124 Messina, Italy

e-mail: salbro77@tiscali.it

123

Neurol Sci

DOI 10.1007/s10072-013-1304-1

CT was also negative. Moreover, she had no oral or genital

ulcerations, eye or skin lesions, leading to the proper

diagnosis. The diagnosis of neurological involvement in

BD is done mainly by clinical means since no specific test

for NBD, to date, exist, although an association with HLA

type B51 has been reported (in 60–70 % of Turkish and

Japanese patients and only 10–20 % of Europeans). Also

brain MRI lesions are not specific, although the involve-

ment of the upper brainstem, thalamus and basal ganglia is

more common [2].

To the best of our knowledge, only a few cases of NBD

presenting with psychiatric symptoms has been so far

described [3–5].

In the case report by Aydin et al. [4], Behcet’s disease

presented with affective symptoms, which recovered after

corticosteroid therapy, while Nakano et al. [5] described a

patient affected by Neuro-Behcet’s disease with early onset

of bipolar mood disorder.

Interestingly, both the patients’ brain MRI showed clear

swelling of the brain stem area, especially in the pons,

confirming the important role of the brain stem aminergic

nuclei in determining mood and anxiety disorders.

On the other hand, in the report by Deniz et al. [3], the

authors have hypothesized that their patient psychotic

symptoms could be due to the involvement of the limbic

system, as in our case. Indeed, the limbic system, including

the amygdala, has long been implicated in the pathogenesis of

psychotic spectrum disorders as well as mood disorders. Both

positive and negative symptoms can be attributed to functions

supported by the limbic system or its networks. The limbic

system has extensive afferent and efferent projections to

multiple brain regions, and it has been supposed that the

significant and selective disruption of fronto-temporal

connectivity is sufficient to determine a phenocopy of

schizophrenia [6].

In conclusion, with our report we want to underline the

importance of considering NBD as a possible factor in psy-

chiatric symptom when an organic aetiology is suspected.

References

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neurological involvement in Behcet’s disease: evaluation of 200

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2. Al-Araji A, Kidd DP (2009) Neuro-Behcet’s disease: epidemiol-

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192–204

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Kuloglu M (2009) A case study of neuro-psycho-Behcet’s

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Fig. 1 A T2-hyperintense lesion in the right amygdala

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