Hisham Hamdalla

Neurodegeneration in frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9orf72 is linked to TDP-43 pathology and not associated with aggregated forms of dipeptide repeat proteins

A hexanucleotide expansion in C9orf72 is the major genetic cause of inherited behavioural variant Frontotemporal dementia (bvFTD) and motor neurone disease (MND), although the pathological mechanism(s) underlying disease remains uncertain.

Relapsing cerebral amyloid angiopathy-related inflammation: the wax and the wane

Cerebral amyloid angiopathy-related inflammation (CAA-I) is a rare variant of cerebral amyloid angiopathy (CAA). Its precise pathophysiology remains uncertain and we currently have limited evidence on which immunosuppressive agents are the most effective in its treatment. The disease course of CAA-I disorders can vary from an isolated clinical event to recurrent episodes. We present a case of biopsy-confirmed CAA-I that gives insight into its potential relapsing nature and the challenges of its long-term management.

PO197 Bulbospinal syndrome in a 17 years old

A 17 year old man with a 9 month history of progressive speech and swallowing difficulties as well as weight loss was admitted to hospital with pneumonia. He and his family noticed twitches of his upper limbs. No weakness or sensory symptoms in the limbs. His hearing and vision were normal. His grandfather had problems with swallowing and dropping things in his seventies. On examination he had myopathic facies with myoclonic jerks in the upper limbs.The tongue was wasted, fasciculating and weak. The neck muscles were strong and eye movements full. The limbs examination revealed no wasting with fasciculations in paraspinal muscles, normal power and symmetrical reflexes. There were no sensory, cerebellar or extrapyramidal features. Routine bloods were normal and an MRI of the neuroaxis as well as CT chest abdomen and pelvis were unremarkable. NCS/EMG was consistent with anterior horn cell disorder and EEG showed multiple paroxysmal generalised spike and wave. Genetic testing including Kennedy’s, Brown-Vialetto-Van Laere Syndrome were negative although pathogenic mutations FUS (Fused in Sarcoma) confirmed FUS MND. FUS MND is a rare cause of familial MND accounting for 4% of all cases with mutant FUS altering global RNA splicing.

A progressive multifocal conundrum

A 62-year-old right-handed woman was referred from ophthalmology in 2009, with a 5-year history of episodic and then more persistent balance difficulty. This was particularly noticeable during tasks requiring depth perception, such as walking down stairs, in the dark and when walking on uneven surfaces. She reported visual ‘bobbing’ when walking, with occasional vertigo, particularly following sudden head movements. As her unsteadiness progressed, she developed double vision on horizontal gaze, with the false image appearing askew (both horizontal and vertical separation). This was most noticeable during tasks requiring fast-tracking eye movements, such as scanning supermarket shelves. By early 2008, she had a ‘droopy’ left eyelid, worse in the evenings but with no limb weakness or difficulty with swallow or speech. Over the years, she developed left arm clumsiness and ‘slowing’ of movements. She now needed a walking stick for support. There was no weight loss, difficulty with hearing or tinnitus. She took treatment for hypertension and hypercholesterolaemia: her medications included bisoprolol, aspirin and atorvastatin. Eight years earlier, she had a melanoma removed from her left thigh. As a child, she had recurrent urinary tract infections complicated by pyelonephritis and requiring intravenous antibiotics; it was unclear as to whether she received aminoglycoside antibiotics. She did not smoke cigarettes and drank minimal alcohol. Her mother had died in her fifties from myocardial infarction and father had died in his fifties from complications of rheumatic heart disease. Her mother had suffered frequent debilitating headaches, diagnosed as migraines by a neurologist. She was one of twins, but her male co-twin died aged 36 h from unknown cause. A second brother, who also had migraine, died aged 54 years from myocardial infarction. She had two healthy children aged 38 and 36 years. On examination, there was no evidence of autonomic involvement. Her cognition was normal, with congruent mood. …