Pathological gambling associated with CADASIL: an unusual manifestation

This paper details a report concerning a case of PG associated with Cerebral Autosomal Dominant Arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). CADASIL is an inherited small artery disease caused by mutations of the NOTCH-3 gene on chromosome 19 [1]. Usually, the first manifestations are attacks of migraine with aura, observed in 20–30 % of patients. Ischemic diseases, the most common clinical manifestations, are reported in 60–80 % of patients, generally during the fourth or fifth decade. Neuropsychiatric manifestations include mood disturbances and various degree of cognitive impairment, observed at all stages of the disorder. Psychiatric symptoms, mainly episodes of mood disturbances, are reported in 10–20 % of patients [2]. Pathological gambling (PG) is as a maladaptive and recurrent pattern of gambling behaviours that persists despite substantial negative consequences for the individual, his/her work and his/ her family. Gambling disorders (referred to as pathological gambling in the DSM-IV) have been recently reclassified in the 5th DSM edition under the category of ‘‘Addictions and Related Disorders’’ because of similarities to substance use disorder (SUD) (i.e. genetic predisposition, treatment response, clinical characteristics, cognitive deficits and underlying neurobiological mechanisms) [3]. A 39-yearold married male, unemployed and genetically diagnosed with CADASIL, carrying a heterogeneous mutation (R90C in the exon 3) of the NOTCH-3 on chromosome 19 p13.213.1 [1], was hospitalized to our neurological outpatient clinic for an episode of transient confusion. His family history revealed that his mother, suffering from CADASIL, died at age of 76 years after a stroke. Our patient had also a history of frequent attacks of migraine without aura since the age of 20 years. Furthermore, he and his relatives denied depressive episodes or previous diagnosis of mood disorder, and he did not display any sleep or eating disorders at the time of the visit. About 6 months before, he started to gamble every day, mainly football betting, slot machines and national lottery, cumulating about 40.000 euros in debts due to gambling. His wife reported that he had become excessively talkative, impulsive and verbally aggressive. During the hospitalization, his labile confusion completely resolved in a few days. Magnetic Resonance Imaging (MRI) of the brain revealed severe leukoencephalopathy with confluent and discrete, fairly symmetric T2 hyperintense foci in the deep and subcortical white matter of the cerebral hemispheres. Similar foci were present in the brainstem, thalami, basal ganglia and the subcortical white matter of anterior temporal lobes (Fig. 1). He had begun to impulse buy multiple items also make many unnecessary purchases for him or his family. When his mental condition was assessed, he showed no confirmation of delusions or hallucinations, but he did have labile moods, poor impulse control, and made grandiose plans. He demonstrated no insight into the changes in his personality and behaviour. Due to a suspected gambling disorder, neuropsychological testing was performed by a clinical psychologist. To evaluate his comprehensive & Domenico Bosco nico_bosco@libero.it