Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) masquerading as CNS demyelination

Abstract

Abstract Background CADASIL is the most common single-gene disorder causing ischemic stroke. CADASIL has been linked to mutations in NOTCH3 gene, due to heterozygous missense mutations. The disease is of insidious onset, presenting with initial clinical features in third and fourth decade of life. However, it is now being increasingly acknowledged that individual clinical presentation, age, time of onset as well as disease severity are quite varied among patients with CADASIL most likely leading to under- or mis-diagnosis. The authors thereby report a genetically confirmed case of CADASIL with atypical clinical course and findings. Case presentation A 48-year-old woman presented with complaints of episodic headache, relapsing–remitting neurological illness, progressive cognitive impairment, and acute-onset loss of speech and ambulation. She was earlier being treated as a case of CNS demyelination for 10 years. On examination, vital parameters were within normal limits. Neurological examination revealed that the patient was drowsy, not verbalizing, not obeying commands, with movement of all four limbs on painful stimuli, hypertonia of all limbs, grade 3 + deep tendon reflexes, bilateral striatal toe and extensor plantar response. Magnetic resonance imaging of brain showed involvement of anterior temporal lobe and external capsule along with multiple acute infarcts. Cerebrospinal fluid analysis was found to be normal. Exome sequencing revealed heterozygous missense mutation in exon 2 of NOTCH3 gene. A definite diagnosis of CADASIL was made and patient was started on fluoxetine and aspirin, following which there was significant improvement over 4–6 weeks. Patient is able to carry out daily activities independently although continues to have mild persistent cognitive impairment with excessive talking and over familiarity. Conclusions As CADASIL has a relapsing and partially remitting course with frequently observed varied clinical presentation, patients may receive treatment for demyelination which may not be necessary. Hence, detailed family history along with knowledge of characteristic magnetic resonance imaging findings seen in CADASIL can help discern the diagnosis.