Hereditary transthyretin amyloidosis presenting with prominent autonomic dysfunction.

A 56-year-old man reported 2 years of slowly progressive exertional fatigue, presyncope, paraesthesia, generalised weakness and nocturnal bowel frequency. He had an abnormal Valsalva ratio and significant postural hypotension. Serum N-terminal pro-B-type natriuretic peptide and troponin T were elevated. Transthoracic echocardiogram identified thickening of the biventricular walls, interatrial septum and atrioventricular valve leaflets. Global longitudinal strain was reduced with relative apical sparing, suspicious for cardiac amyloidosis. Technetium-99m and 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy supported a diagnosis of transthyretin amyloidosis (ATTR). However, urinary Bence Jones protein (kappa) was identified despite a normal kappa/lambda light chain ratio and no serum paraprotein. Bone marrow and buccal biopsy provided histological confirmation of amyloid. The bone marrow had no evidence of plasma cell dyscrasia but positive TTR immunohistochemistry. The patient had a T60A genetic mutation for hereditary ATTR. Overlapping cardiac and autonomic symptoms prompt an amyloid workup, which then must distinguish AL amyloid from ATTR pathology.

Hypoactive-hypoalert behaviour and thalamic hypometabolism due to intracranial hypotension.

A 47-year-old man presented with a 9-year history of a hypoalert hypoactive behaviour syndrome, caused by the deep brain swelling variant of spontaneous intracranial hypotension. Along with apathy with retained cognition, he had stable ataxia, impaired upgaze and episodes of central apnoea. MRI brain showed a sagging brainstem, pointed ventricles and reduced angle between the vein of Galen and the straight sinus, but no meningeal enhancement or subdural collections. A dopamine transporter scan showed preganglionic dopamine receptor deficiency; a fluorodeoxy glucose positron emission tomography scan showed bilateral hypothalamic hypometabolism. This variant of spontaneous intracranial hypotension may alter deep brain functioning within the basal ganglia and thalamus, causing the hypoactive-hypoalert behaviour phenotype.

Secular trends in disease modifying treatment and expenditure in multiple sclerosis: A longitudinal population study in the north of Ireland.

BACKGROUND: The epidemiology of multiple sclerosis (MS) is important for planning disease modifying therapy (DMT). Secular changes in the use of DMT in MS can guide future service development. METHODS: A population study of the prevalence of multiple sclerosis was completed in the west of Northern Ireland - a defined geographic area making up the Western Health and Social Care Trust (WHSCT). The use, category and cost of DMT for the MS population in the WHSCT were measured over 11 years. RESULTS: The WHSCT had a recorded prevalence of MS of 238.4/100,000 (95%CI 221.5-256.5) in 2018. DMT use increased over threefold in 11 years. Four hundred and nine (57%) of 720 MS patients were taking a DMT by 2018. The annual expenditure of DMT drugs had increased sixfold over ten years to £5,301,198 in 2018 (using 2018 prices), reflecting both an increase in DMT use and a switch to more intensive DMTs. Younger MS patients were more likely to be taking a DMT (P<0.001). CONCLUSION: DMT use and cost have been increasing among the MS population in the Northern Ireland. There has been a temporal switch to more efficacious DMTs. Future research should monitor the cost-effectiveness and equity of treatment of MS patients.