Clinical Neurology and Neurosurgery 127 (2014) 13–14
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Neuropsychiatric features in Behc¸et’s disease: A case report Cornelia van Ham a , Didier Schrijvers a,b,∗ , Livia De Picker b , Frans Vandendriessche a , Bernard Sabbe a,b a b
Psychiatric Hospital Duffel, Duffel, Belgium Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium
a r t i c l e
i n f o
Article history: Received 15 October 2013 Received in revised form 26 August 2014 Accepted 20 September 2014 Available online 2 October 2014 Keywords: Behc¸et’s disease Neuro-Behc¸et’s Manic episode
1. Introduction
3. Case report
Behc¸et’s disease (BD) is a multisystem disorder of unknown aetiology, characterised by inflammatory processes in several locations. Recurrent oral and genital ulcerations and uveitis eye inflammation represent the most important symptoms. Other possible symptoms include arthritis, skin rash and neurological abnormalities. The disease was first described in 1937 by Turkish dermatologist Hulusi Behc¸et. Little is known about the psychiatric symptoms of BD. This paper reports the case of a patient diagnosed with Behc¸et’s after being admitted to a psychiatric hospital with a manic episode and provides a literature review on neuropsychiatric features of BD.
A 34-year-old Moroccan man was admitted to psychiatric hospital after displaying bizarre behaviour, harassing children on the street and expressing suicidal intentions. Psychiatric examination upon admission pointed out an appearance of self-neglect, yet looking age-appropriate. Orientation in time, space and person was preserved, but the patient demonstrated impaired capacity for sustained concentration in the interview. He exhibited disinhibition, loss of decorum and reduced sleep, with psychomotor agitation, pressured speech and garrulousness. Manifest hallucinations, delusions and grandiose ideas were absent, nor was there an increase in goal-oriented behaviour. The patient mentioned experiencing depressive mood. Clinical neurological examination did not demonstrate any significant findings. Routine blood work appeared normal and toxicological screening was negative. After a few weeks the patient developed oral ulcerations, an erythematous chest rash and genital ulcerations. These symptoms were suggestive of BD and prompted further investigations. Heteroanamnesis revealed the patient to have been hospitalised for gait abnormalities four years earlier. Cerebral imaging at that time showed a space-occupying lesion, signifying either a malignant or inflammatory process. After subsequent unsuccessful treatment with ampicillin, ceftriaxone, metronidazole and acyclovir, histopathological investigation of a brain biopsy ruled out a malignant lesion, revealing parenchymal and perivascular inflammation with reactive gliosis. Thereafter, patient’s clinical condition aggravated; he became confused but then left the hospital against
2. Methodology A search of relevant literature was performed in “Pubmed”, using search strings: “behcet disease/syndrome” and “psychiatry”, “psychiatric symptoms”, “bipolar disorder”, “psychosis” and “mood/affective disorder”.
∗ Corresponding author at: Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Faculty of Medicine and Health Sciences, Campus Drie Eiken, R 3.22, Universiteitsplein 1, 2610 Wilrijk-Antwerp, Belgium. Tel.: +32 15304030. E-mail addresses: [email protected], [email protected] (D. Schrijvers). http://dx.doi.org/10.1016/j.clineuro.2014.09.010 0303-8467/© 2014 Elsevier B.V. All rights reserved.
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C. van Ham et al. / Clinical Neurology and Neurosurgery 127 (2014) 13–14
medical advice. Patient also mentioned a previous hospitalisation in Morocco, where he was treated with colchicine for indications unknown. 4. Additional investigations During current admission a CT scan of the patient’s brain revealed a small hypodense lesion in the right frontal white matter, presumably caused by aforesaid biopsy. MR imaging showed a right frontal area of perivascular gliosis, connected to a penetrating vascular structure through the basal ganglia. An early demyelination was noticed in the mesencephalon’s cerebral peduncle. Cerebral SPECT showed hypoperfusion over the left frontal and temporal lobes. EEG examination displayed mild, aspecific cortical dysfunction. Genetic testing for a BD marker proved the patient to be a genetic carrier of HLA-B51 leucocyte antigen, present in about 60% of Behc¸et’s patients. Finally, a “skin prick test” confirmed a positive pathergy reaction, a cutaneous phenomenon typical for Behc¸et’s: a needle pierced 5 mm deep into the patient’s forearm resulted in the development of a red bump around the insertion site 24–48 h later. 5. Diagnosis Abovementioned results confirmed the diagnosis of BD according to the international diagnostic criteria. Patient also met DSM-IV-TR criteria for a manic episode, albeit an atypical presentation without mood elevation and grandiose ideas. As our patient also experienced an increased energy level, DSM-5 criteria were met as well. 6. Treatment Initial treatment consisted of pipamperon 3× 20 mg and lormetazepam 2 mg daily. Continuous restiveness, agitation and confusion prompted the addition of 80 mg clotiapine. After a week this treatment regime proved inadequate and pipamperon and clotiapine were gradually switched to olanzapine 10 mg and valproic acid 1000 mg daily. After confirmation of BD, anti-inflammatory treatment was installed (colchicine 1.5 mg, methylprednisolone 1 mg/kg and azathioprine 100 mg daily), changed into azathioprine monotherapy after three weeks. A few days after initiation of anti-inflammatory therapy a positive effect was noticed on oral and genital ulcerations. Over the next three months the patient significantly improved behaviourally and after discharge continued to function well with ambulatory psychiatric follow-up. Azathioprine 50 mg daily was sustained as maintenance treatment. Although there are no controlled trials on the treatment of NBD, azathioprine is often used to prevent relapse. In our case, this was combined with psychoeducation of the patient and his family for a period of two years without any observed relapse. 7. Discussion This paper described a man hospitalised in a manic condition and subsequently diagnosed with BD.
BD is rare in Europe (0.12–7.5 per 100,000 inhabitants); prevalence is significantly higher in countries close to the ancient Silk Road, travelling through East Asia (13.5–20 per 100,000) to the Mediterranean (80–370 per 100,000). Its symptoms mostly emerge in young men [1]. The characteristic inflammatory processes are mostly caused by vasculitic involvement of large and small arterial and venous vessels. This causes the disease to manifest itself in various locations in the body and tends to complicate diagnosis. A minority of patients (5–20%) will also exhibit neurological complications, defined as neuro-Behc¸et’s disease (NBD) [2]. Neuro-Behc¸et’s underlying pathology is divided in vascular and parenchymal lesions. Patients with vascular lesions display intracranial hypertension with papilledema, headaches, focal neurological deficits and seldom pyramidal symptoms. Contrasting, parenchymal lesions cause pyramidal symptoms in 96% of patients and behavioural alterations in half. A minority also suffer from hypersomnia, sensory and gait aberrations and hearing and sight problems. Only 2% of cases exhibit psychiatric symptoms, such as acute psychosis. Our patient case clearly concerns NBD with parenchymal involvement, corresponding with the medical history of gait abnormality and pseudotumoral process. The histopathological and imaging findings also match literature description of parenchymal NBD. It is unclear whether the psychiatric symptoms were also due to the underlying NBD. Evidence from literature on the causal relationship between psychiatric symptoms and NBD is limited to four case reports. One report links NBD to bipolar disorder [3], in which the mood disorder manifested itself during an NBD exacerbation. Other reports describe a psychotic patient with an NBD exacerbation and a patient whose affective symptoms preceded BD [4,5]. Given the lack of psychiatric history, we might presume our patient’s psychiatric condition to be caused by NBD parenchymal brain damage. An explanatory hypothesis might refer to the associated neuroinflammatory processes, which are currently under investigation as causative factors in many psychiatric conditions. However, studies exploring the relation between neuroinflammation and psychiatric symptoms are still inconclusive at this point. Little research has investigated the treatment of NBD, but glucocorticoids combined with azathioprine appear to be effective. Alternatives include cyclophosphamide, TNF␣ inhibitors and interferon-␣. Colchicine is mainly effective for dermatological sequellae. In this case, anti-inflammatory treatment leads to prompt resolution of dermatological symptoms and subsequent normalisation of mood and behaviour in three months’ time. References [1] Yurdakul S, Hamuryudan V, Yazici H. Behcet syndrome. Curr Opin Rheumatol 2001;13:18–22. [2] Akman-Demir G, Serdaroglu P, Tasc¸i B. The neuro-Behcet study group. Clinical patterns of neurological involvement in Behc¸et disease: evaluation of 200 patients. Brain 1999;122:2171–82. [3] Alevizos B, Anagnostara C, Christodoulou GN. Resistant bipolar disorder precipitated by Behc¸et’s syndrome. Bipolar Disord 2004;6:260–3. [4] Deniz O, Cayköylü A, Vural G, Albayrak Y, Temel S, Aydin I, et al. A case study of neuro-psycho-Behc¸et’s syndrome presenting with psychotic attack. Clin Neurol Neurosurg 2009;111:877–9. [5] Aydin N, Aydin MD, Deniz O, Kirpinar I. Neuro-Behc¸et’s disease involving the pons with initial onset of affective symptoms. Eur Arch Psychiatry Clin Neurosci 2002;252:44–6.
©2014 Elsevier
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Neuropsychiatric features in Behc¸et’s disease: A case report Cornelia van Ham a , Didier Schrijvers a,b,∗ , Livia De Picker b , Frans Vandendriessche a , Bernard Sabbe a,b a b
Psychiatric Hospital Duffel, Duffel, Belgium Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium
a r t i c l e
i n f o
Article history: Received 15 October 2013 Received in revised form 26 August 2014 Accepted 20 September 2014 Available online 2 October 2014 Keywords: Behc¸et’s disease Neuro-Behc¸et’s Manic episode
1. Introduction
3. Case report
Behc¸et’s disease (BD) is a multisystem disorder of unknown aetiology, characterised by inflammatory processes in several locations. Recurrent oral and genital ulcerations and uveitis eye inflammation represent the most important symptoms. Other possible symptoms include arthritis, skin rash and neurological abnormalities. The disease was first described in 1937 by Turkish dermatologist Hulusi Behc¸et. Little is known about the psychiatric symptoms of BD. This paper reports the case of a patient diagnosed with Behc¸et’s after being admitted to a psychiatric hospital with a manic episode and provides a literature review on neuropsychiatric features of BD.
A 34-year-old Moroccan man was admitted to psychiatric hospital after displaying bizarre behaviour, harassing children on the street and expressing suicidal intentions. Psychiatric examination upon admission pointed out an appearance of self-neglect, yet looking age-appropriate. Orientation in time, space and person was preserved, but the patient demonstrated impaired capacity for sustained concentration in the interview. He exhibited disinhibition, loss of decorum and reduced sleep, with psychomotor agitation, pressured speech and garrulousness. Manifest hallucinations, delusions and grandiose ideas were absent, nor was there an increase in goal-oriented behaviour. The patient mentioned experiencing depressive mood. Clinical neurological examination did not demonstrate any significant findings. Routine blood work appeared normal and toxicological screening was negative. After a few weeks the patient developed oral ulcerations, an erythematous chest rash and genital ulcerations. These symptoms were suggestive of BD and prompted further investigations. Heteroanamnesis revealed the patient to have been hospitalised for gait abnormalities four years earlier. Cerebral imaging at that time showed a space-occupying lesion, signifying either a malignant or inflammatory process. After subsequent unsuccessful treatment with ampicillin, ceftriaxone, metronidazole and acyclovir, histopathological investigation of a brain biopsy ruled out a malignant lesion, revealing parenchymal and perivascular inflammation with reactive gliosis. Thereafter, patient’s clinical condition aggravated; he became confused but then left the hospital against
2. Methodology A search of relevant literature was performed in “Pubmed”, using search strings: “behcet disease/syndrome” and “psychiatry”, “psychiatric symptoms”, “bipolar disorder”, “psychosis” and “mood/affective disorder”.
∗ Corresponding author at: Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Faculty of Medicine and Health Sciences, Campus Drie Eiken, R 3.22, Universiteitsplein 1, 2610 Wilrijk-Antwerp, Belgium. Tel.: +32 15304030. E-mail addresses: [email protected], [email protected] (D. Schrijvers). http://dx.doi.org/10.1016/j.clineuro.2014.09.010 0303-8467/© 2014 Elsevier B.V. All rights reserved.
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C. van Ham et al. / Clinical Neurology and Neurosurgery 127 (2014) 13–14
medical advice. Patient also mentioned a previous hospitalisation in Morocco, where he was treated with colchicine for indications unknown. 4. Additional investigations During current admission a CT scan of the patient’s brain revealed a small hypodense lesion in the right frontal white matter, presumably caused by aforesaid biopsy. MR imaging showed a right frontal area of perivascular gliosis, connected to a penetrating vascular structure through the basal ganglia. An early demyelination was noticed in the mesencephalon’s cerebral peduncle. Cerebral SPECT showed hypoperfusion over the left frontal and temporal lobes. EEG examination displayed mild, aspecific cortical dysfunction. Genetic testing for a BD marker proved the patient to be a genetic carrier of HLA-B51 leucocyte antigen, present in about 60% of Behc¸et’s patients. Finally, a “skin prick test” confirmed a positive pathergy reaction, a cutaneous phenomenon typical for Behc¸et’s: a needle pierced 5 mm deep into the patient’s forearm resulted in the development of a red bump around the insertion site 24–48 h later. 5. Diagnosis Abovementioned results confirmed the diagnosis of BD according to the international diagnostic criteria. Patient also met DSM-IV-TR criteria for a manic episode, albeit an atypical presentation without mood elevation and grandiose ideas. As our patient also experienced an increased energy level, DSM-5 criteria were met as well. 6. Treatment Initial treatment consisted of pipamperon 3× 20 mg and lormetazepam 2 mg daily. Continuous restiveness, agitation and confusion prompted the addition of 80 mg clotiapine. After a week this treatment regime proved inadequate and pipamperon and clotiapine were gradually switched to olanzapine 10 mg and valproic acid 1000 mg daily. After confirmation of BD, anti-inflammatory treatment was installed (colchicine 1.5 mg, methylprednisolone 1 mg/kg and azathioprine 100 mg daily), changed into azathioprine monotherapy after three weeks. A few days after initiation of anti-inflammatory therapy a positive effect was noticed on oral and genital ulcerations. Over the next three months the patient significantly improved behaviourally and after discharge continued to function well with ambulatory psychiatric follow-up. Azathioprine 50 mg daily was sustained as maintenance treatment. Although there are no controlled trials on the treatment of NBD, azathioprine is often used to prevent relapse. In our case, this was combined with psychoeducation of the patient and his family for a period of two years without any observed relapse. 7. Discussion This paper described a man hospitalised in a manic condition and subsequently diagnosed with BD.
BD is rare in Europe (0.12–7.5 per 100,000 inhabitants); prevalence is significantly higher in countries close to the ancient Silk Road, travelling through East Asia (13.5–20 per 100,000) to the Mediterranean (80–370 per 100,000). Its symptoms mostly emerge in young men [1]. The characteristic inflammatory processes are mostly caused by vasculitic involvement of large and small arterial and venous vessels. This causes the disease to manifest itself in various locations in the body and tends to complicate diagnosis. A minority of patients (5–20%) will also exhibit neurological complications, defined as neuro-Behc¸et’s disease (NBD) [2]. Neuro-Behc¸et’s underlying pathology is divided in vascular and parenchymal lesions. Patients with vascular lesions display intracranial hypertension with papilledema, headaches, focal neurological deficits and seldom pyramidal symptoms. Contrasting, parenchymal lesions cause pyramidal symptoms in 96% of patients and behavioural alterations in half. A minority also suffer from hypersomnia, sensory and gait aberrations and hearing and sight problems. Only 2% of cases exhibit psychiatric symptoms, such as acute psychosis. Our patient case clearly concerns NBD with parenchymal involvement, corresponding with the medical history of gait abnormality and pseudotumoral process. The histopathological and imaging findings also match literature description of parenchymal NBD. It is unclear whether the psychiatric symptoms were also due to the underlying NBD. Evidence from literature on the causal relationship between psychiatric symptoms and NBD is limited to four case reports. One report links NBD to bipolar disorder [3], in which the mood disorder manifested itself during an NBD exacerbation. Other reports describe a psychotic patient with an NBD exacerbation and a patient whose affective symptoms preceded BD [4,5]. Given the lack of psychiatric history, we might presume our patient’s psychiatric condition to be caused by NBD parenchymal brain damage. An explanatory hypothesis might refer to the associated neuroinflammatory processes, which are currently under investigation as causative factors in many psychiatric conditions. However, studies exploring the relation between neuroinflammation and psychiatric symptoms are still inconclusive at this point. Little research has investigated the treatment of NBD, but glucocorticoids combined with azathioprine appear to be effective. Alternatives include cyclophosphamide, TNF␣ inhibitors and interferon-␣. Colchicine is mainly effective for dermatological sequellae. In this case, anti-inflammatory treatment leads to prompt resolution of dermatological symptoms and subsequent normalisation of mood and behaviour in three months’ time. References [1] Yurdakul S, Hamuryudan V, Yazici H. Behcet syndrome. Curr Opin Rheumatol 2001;13:18–22. [2] Akman-Demir G, Serdaroglu P, Tasc¸i B. The neuro-Behcet study group. Clinical patterns of neurological involvement in Behc¸et disease: evaluation of 200 patients. Brain 1999;122:2171–82. [3] Alevizos B, Anagnostara C, Christodoulou GN. Resistant bipolar disorder precipitated by Behc¸et’s syndrome. Bipolar Disord 2004;6:260–3. [4] Deniz O, Cayköylü A, Vural G, Albayrak Y, Temel S, Aydin I, et al. A case study of neuro-psycho-Behc¸et’s syndrome presenting with psychotic attack. Clin Neurol Neurosurg 2009;111:877–9. [5] Aydin N, Aydin MD, Deniz O, Kirpinar I. Neuro-Behc¸et’s disease involving the pons with initial onset of affective symptoms. Eur Arch Psychiatry Clin Neurosci 2002;252:44–6.
©2014 Elsevier
