CASE REPORT Case report Fits and strokes Pankaj Sharma, Tao Wang, Morris J Brown, Anthony H V Schapira A 41-year-old right-handed engineer was admitted in MRI head scan showed no substantial change. A muscle 1998 with a 10-year history of absence seizures. The biopsy was normal. seizures were characterised by symptoms of olfactory déjà vu. During the seizures witnesses reported that the We screened the patient’s DNA for CADASIL patient was able to walk and undertake complex tasks. (cerebral autosomal dominant arteriopathy with The seizures, of which the patient had no recollection, subcortical infarcts and leukoencephalopathy). A diseaselasted for a few minutes and were causing mutation C→T583 was followed by several hours of found in exon 4.1 The patient’s 67 lethargy. They would occasionally year old mother also carried the occur following binge drinking. He mutation but reported no history of had a past history of migraine with cerebral ischaemic events. When visual aura. One of the patient’s last seen in Feb, 2001, the patient four siblings one was said to have remained stable. “multiple sclerosis” but the exact nature of the diagnosis was not CADASIL is an inherited adultclear. His mother had thyroid onset disease due to mutations in disease and migraine and his father the transmembrane receptor of the had diabetes but there was no other Notch3 gene (on chromosome family history of note. On 19q12) which either create or examination the patient had vitiligo. destroy a cysteine residue.2,3 The His BP was 120/80 mm Hg. He acronym CADASIL describes a seemed to have brisker tendon clinical syndrome characterised reflexes on the left side and foot most commonly by cerebral tapping was marginally diminished Magnetic resonance image of brain ischaemic events (84%), dementia on the left. His abstract reasoning (31%), migraine with aura (22%) was mildly impaired. The remainder of the examination and mood disturbances (20%).4 6% of patients with was normal. The following investigations were normal, CADASIL have grand mal seizures4 but epileptic events negative or non-diagnostic: full blood count, liver as a presenting feature of CADASIL are rare. The mean function, thyroid function, ESR (8 mm/h), syphilis age of onset of symptoms is 45 years and most patients die serology, blood lactate, amino acid profile, vitamin B12, by 65 years, as there is no available treatment. MRI of the folate, lupus anticoagulant, proteins C & S, activated head shows ischaemic changes with extensive white protein C resistance, antibody to thrombin III, matter signal abnormalities. Reduplication of the elastic autoantibody screen, angiotensin converting enzyme media and granular material in the media of affected concentrations in serum and cerebrospinal fluid (CSF), arteries is seen in biopsy samples. The cerebral visual, brainstem and somatosensory evoked potentials, arteriopathy is slowly progressive resulting in thickening magnetic resonance imaging (MRI) of the neck vessels, and fibrosis of small and medium sized penetrating and cardiac echocardiography. An electroencephalogram arteries with consequent narrowing of their lumen. With showed only mild non-specific left temporal disturbances availability of genetic testing1 the condition is becoming of cerebral activity. CSF examination showed an opening increasingly recognised. Sporadic cases of CADASIL are pressure of 16·5 cm of water, glucose 4 mmol/L likely to be more common than previously thought.5 (peripheral 7 mmol/L), protein 0·96 g/L, lymphocytes CADASIL is an important cause of ischaemic strokes, 2⫻106/L, red cells 1⫻106/L, normal CSF lactate, and no which should be considered especially in young patients, and can present with seizures, as illustrated by our oligoclonal bands. MRI of his head (figure) showed patient. multiple areas of high signal in the white matter bilaterally and one in the pons posteriorly. These areas were We thank Jean-Claude Baron for helpful comments on this manuscript. confluent periventricularly. 4 months later the patient was readmitted following a sudden onset of unsteadiness of References gait, diplopia, nausea, and vertigo. Over the next 48 h he 1 Wang T, Sharma SD, Fox N, Rosser M, Brown MJ, Sharma P. developed slurred speech. On examination he had ataxia Description of a simple test for CADASIL disease and determination with multi-directional and rotatory nystagmus. There was of mutation frequencies in sporadic ischaemic stroke and dementia patients. J Neurol Neurosurg Psychiatry 2000; 69: 652–24. marked cerebellar incoordination in the left arm. A repeat 2 Lancet 2001; 358: 120 Clinical Pharmacology Unit, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK (P Sharma PhD, T Wang PhD, M J Brown MD); and University Department of Clinical Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London (Prof A H V Schapira DSc) Correspondence to: Dr Pankaj Sharma (E-mail: psharma@hgmp.mrc.ac.uk) 120 3 4 5 Joutel A, Corpechot C, Ducros A, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996; 383: 707–10. Joutel A, Vahedi K, Corpechot C, et al. Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet 1997; 350: 1511–15. Chabriat H, Vahedi K, Iba-Zizen MT, et al. Clinical spectrum of CADASIL: a study of 7 families. Lancet 1995; 346: 934–39. Joutel A, Dodick DD, Parisi JE, Cecillion M, Tournier-Lasserve E, Bousser MG. De novo mutation in the Notch3 gene causing CADASIL. Ann Neurol 2001; 47: 388–91. THE LANCET • Vol 358 • July 14, 2001 For personal use. Only reproduce with permission from The Lancet Publishing Group.