Neuropsychiatric Symptoms of CADASIL

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL) is an inherited small-artery disease of mid-adulthood caused by mutations of the NOTCH3 gene. The disease is responsible for widespread white-matter Iesions associated with lacunar infarctions in varinus subcortical areas. The disease is responsible for migraine with aura and ischemic strokes, and is associated with various degrees of cognitive impairment and with mood disturbances. CADASIL is considered as a unique model to investigate what is known as "subcortical ischemic vascular dementia. "Recent data suggest that the number of lacunar infarctions and severity of cerebral atrophy are the main magnetic resonance imaging markers associated with cognitive and motor disabilities in this disorder. Mood disturbances are reported in 10% to 20% of patients, most often in association with cognitive alterations. Their exact origin remains unknown; the presence of ischemic lesions within the basal ganglia or the frontal white matter may promote the occurrence of these symptoms. Further studies are needed to better understand the relationships between cerebral lesions and both cognitive and psychiatric symptoms in this small-vessel disease of the brain.

Bipolar disorder against a background of a rare vascular dementia

“…2 Chabriat et al estimated that about 5 per cent of CADASIL patients suf fer from mania. 9 A study carried out by Valenti et al was considered to be the first to approach the topic of mood disorders in CADASIL with a systemic and structured assessment.…”

“…2 CADASIL occurs world wide and has been reported in many ethnic groups. The prevalence and disease burden are still undeter mined.…”

Migraine and movement disorders

“…Basal ganglia (BG), which receives inputs from thalamus and all cortical regions projecting back to the BG, mostly through BG-thalamo-cortical loops, seems to be involved in the sensory, emotional and cognitive integration of pain information between cortical and thalamic regions [11][12][13]. Brain imaging studies have shown decreased activation in the BG of migraineurs versus controls in the interictal period [14], increased activation (blood flow) during the ictal state and other non specific lesions [15,16]. More recently, significant differences in gray matter volume and function in response to pain have been observed interictally in the BG in migraineurs with higher frequency of attacks versus those with lower frequency [17].…”

Hypomanic episode in CADASIL syndrome

“…With this, the age of onset and clinical presentations are multifactorious. Attacks of migraine with aura are the first clinical manifestation in 20-30% of patients (4). Mood disorders, anxiety disorders, psychotic disorders, adjustment disorders, behavioral disorders, personality disorders, drug addiction, and substance abuse are main psychiatric diagnoses in CADASIL patients (2).…”

“…NOTCH 3 is expressed exclusively from smooth muscle cells located at arterial walls and mutations in the NOTCH 3 gene bring about degeneration of vascular smooth muscle cells and multiple small infarcts at the white matter and deep gray matter (4,11). How the NOTCH 3 gene engenders arteriopathy is unknown.…”