Heritability of frontotemporal dementia

One of my side projects over the past 2 years has been research in the cognitive neurosciences under the supervision of Dr James Burrell at Neuroscience Research Australia (NeuRA). Specifically, we were looking at the heritability of frontotemporal dementia.

Preliminary results from our study were published as a poster at the Australian and New Zealand Association of Neurologists (ANZAN) Annual Scientific Meeting 2014 in Adelaide. I doubt that anyone else at a neurology conference would typeset a poster in Helvetica Neue Light!

Our poster at ANZAN ASM 2014

This culminated in a paper which was accepted in the Journal of Neurology and published in November 2014 (vol 261 no 11). The abstract is reproduced below, along with the correct author affiliations (an error was introduced by the journal subeditors – Professors Kwok, Halliday and Hodges are not affiliated with Concord Repatriation General Hospital).

Po et al. J Neurol 2014

Author Affiliations

Concord Repatriation General Hospital, Sydney, Australia – KP, JB
Sydney Medical School, The University of Sydney, Australia – KP
Neurosciences Research Australia, Sydney, Australia – FL, NG, LB, JK, GH, JH, JB
The University of New South Wales, Sydney, Australia – JK, GH, JH, JB

Abstract

Frontotemporal dementia (FTD) is reportedly highly heritable, even though a recognized genetic cause is often absent. To explain this contradiction, we explored the “strength” of family history in FTD, Alzheimer’s disease (AD), and controls. Clinical syndromes associated with heritability of FTD and AD were also examined. FTD and AD patients were recruited from an FTD-specific research clinic, and patients were further sub-classified into FTD or AD phenotypes. The strength of family history was graded using the Goldman score (GS), and GS of 1-3 was regarded as a “strong” family history. A subset of FTD patients underwent screening for the main genetic causes of FTD. In total, 307 participants were included (122 FTD, 98 AD, and 87 controls). Although reported positive family history did not differ between groups, a strong family history was more common in FTD (FTD 17.2 %, AD 5.1 %, controls 2.3 %, P < 0.001). The bvFTD and FTD-ALS groups drove heritability, but 12.2 % of atypical AD patients also had a strong family history. A pathogenic mutation was identified in 16 FTD patients (10 C9ORF72 repeat expansion, 5 GRN, 1 MAPT), but more than half of FTD patients with a strong family history had no mutation detected. FTD is a highly heritable disease, even more than AD, and patients with bvFTD and FTD-ALS drive this heritability. Atypical AD also appears to be more heritable than typical AD. These results suggest that further genetic influences await discovery in FTD.

Citation

Po K, Leslie FVC, Gracia N, Bartley L, Kwok JBJ, Halliday GM, Hodges JR, Burrell JR. Heritability in frontotemporal dementia: more missing pieces? J Neurol. 2014;261(11):2170–7.

doi: 10.1007/s00415-014-7474-9
PMID: 25156163 (PubMed)

When two SCORPIOs get together

One of the key features of clinical learning at Sydney Medical School are the SCORPIO sessions (SCORPIO apparently stands for “structured, clinical, objective, referenced, problem-orientated, integrated and organised”). With the exception of a few pseudo-SCORPIOs during haematology block, I’ve generally found SCORPIOs to be great learning experiences and I’m quite fortunate that my clinical school reputedly organises more SCORPIOs than the other USyd clinical schools.

Each SCORPIO session generally starts with a short introductory session to outline the session, after which students divide into small groups and rotate around several teaching stations. Each station features either a patient with a certain clinical presentation to solve/discuss – e.g. a young lady with immune thrombocytopenic purpura (ITP) – or known clinical signs to elicit – e.g. a gentleman with a pronounced aortic valve ejection systolic murmur and carotid bruits.

For endocrinology block, the clinical school has organised a SCORPIO each week in lieu of clinical diagnostic skills tutorials. By coincidence our postponed neurology SCORPIO was also held this week, which meant that we had two SCORPIOs today.

Neurology SCORPIO

  • Charcot-Marie-Tooth disease
  • L5 sensorimotor radiculopathy
  • Brachial plexopathy secondary to radiotherapy

Endocrinology SCORPIO 1 (thyroid disorders)

  • Graves’ disease
  • Toxic multinodular goitre
  • Hashimoto’s thyroiditis

After enduring the frustration of most of this week, today’s double SCORPIO clinical day provided a welcome breath of fresh air.

Dysphasie en français

The hospital I work at has an arrangement with the New Caledonian private health fund Caisse de Compensation des Prestations Familiales des Accident du Travail et de Prévoyance Familiales des Travailleurs de la Nouvelle-Caledonie et Dépendances (CAFAT), which means that we regularly have French-speaking patients under our care – many of whom have little command of English.

Recently, I needed to check whether one of our CAFAT patients had any more of her own supply of gabapentin. Having established that she didn’t understand any English, I was forced to deploy my very rudimentary French…

Me: Bonjour madame, je suis le pharmacien… Avez-vous plus de la gabapentine?
Pt: Looks at me blankly. Pharmacien?
Me: Oui. Avez-vous plus de la gabapentine?
Pt: Matin et soir… « unintelligible »
I try a different tack and show her the tablets remaining in her medication drawer.
Me: Voici deux comprimés de la gabapentine. Avez-vous plus?
Pt: Un le matin… « unintelligible »
Me: Oui, mais avez-vous plus de comprimés? Plus?
Pt: « unintelligible »
At this point I give up…
Me: Ok, merci.

I later noted that the reason for admission was a central nervous system (CNS) lesion. At this point I realised that she probably had dysphasia secondary to the CNS lesion… so perhaps it wasn’t (just) my bad French!