Genetic testing in motor neurone disease

A minority (10%–15%) of cases of amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease (MND), are currently attributable to pathological variants in a single identifiable gene. With the emergence of new therapies targeting specific genetic subtypes of ALS, there is an increasing role for routine genetic testing for all those with a definite diagnosis. However, potential harm to both affected individuals and particularly to asymptomatic relatives can arise from the indiscriminate use of genetic screening, not least because of uncertainties around incomplete penetrance and variants of unknown significance. The most common hereditary cause of ALS, an intronic hexanucleotide repeat expansion in C9ORF72, may be associated with frontotemporal dementia independently within the same pedigree. The boundary of what constitutes a possible family history of MND has therefore extended to include dementia and associated psychiatric presentations. Notwithstanding the important role of clinical genetics specialists, all neurologists need a basic understanding of the current place of genetic testing in MND, which holds lessons for other neurological disorders.

Young-onset stroke complicating ulcerative colitis

A 16-year-old girl developed a proximal occlusion of the right middle cerebral artery during a flare-up of acute ulcerative colitis. Although mechanical thrombectomy led to successful middle cerebral artery recanalisation, she required an immediate second thrombectomy due to reocclusion of the same arterial segment. She developed a second ischaemic event 7 days later despite intravenous heparin infusion, later switched to low-molecular-weight heparin, and a third event after 3 days despite the addition of aspirin. We discuss stroke risks in people with inflammatory bowel disease and the uncertainties around anticoagulation and antiplatelet regimens in such cases.

Allgrove syndrome with amyotrophy

Allgrove syndrome is an autosomal recessive disease mostly caused by mutations in the AAAS gene. It has variable clinical features but its cardinal features comprise the triad of achalasia, alacrimia and adrenal insufficiency. It typically develops during the first decade of life, but some cases have second and third decades onset. We describe a 25-year-old woman with Allgrove syndrome who had progressive amyotrophy, achalasia, dry eyes and adrenal insufficiency since childhood. Awareness of its neurological manifestations and multisystem features helps to shorten the time for diagnosis and allow appropriate symptomatic treatment.

Cerebral amyloid angiopathy with related inflammation masquerading as crescendo transient ischaemic attacks

Cerebral amyloid angiopathy with related inflammation (CAA-RI) is an uncommon inflammatory subtype of CAA, with a variety of presentations that can mimic other focal and diffuse neurological disorders. We present a 63-year-old man with recurrent stereotyped focal neurological symptoms, who was initially diagnosed as capsular warning syndrome and treated with antithrombotic therapy. Atypical imaging led to further investigation including a cerebral biopsy, which confirmed CAA-RI; he improved clinically and radiologically with immunosuppression. This case highlights how CAA-RI is often under-recognised and that patients risk receiving inappropriate anticoagulation and delay in starting immunosuppression.