Diagnosis Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Syndrome (2019)

Type of publication:
Journal article

Author(s):
Jabbari E, Holland N, Chelban V, Jones PS, Lamb R, Rawlinson C, Guo T, Costantini AA, Tan MMX, Heslegrave AJ, Roncaroli F, Klein JC, Ansorge O, Allinson KSJ, Jaunmuktane Z, Holton JL, Revesz T, Warner TT, Lees AJ, Zetterberg H, Russell LL, Bocchetta M, Rohrer JD, Williams NM, Grosset DG, Burn DJ, Pavese N, Gerhard A, Kobylecki C, Leigh PN, Church A, Hu MTM, Woodside J, Houlden H, Rowe JB, Morris HR.

Patients at Shrewsbury and Telford Hospital NHS Trust were recruited into this study.

Citation:
JAMA Neurol. 2019 Dec 20 [Epub ahead of print]

Abstract:
IMPORTANCE:
Atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are often misdiagnosed as Parkinson disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes but have not been prospectively studied.

OBJECTIVE:
To define the distinguishing features of PSP and CBS subtypes and to assess their usefulness in facilitating early diagnosis and separation from PD.

DESIGN, SETTING, PARTICIPANTS:
This cohort study recruited patients with APS and PD from movement disorder clinics across the United Kingdom from September 1, 2015, through December 1, 2018. Patients with APS were stratified into the following groups: those with Richardson syndrome (PSP-RS), PSP-subcortical (including PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (including PSP-frontal and PSP-CBS overlap subtypes), MSA-parkinsonism, MSA-cerebellar, CBS-Alzheimer disease (CBS-AD), and CBS-non-AD. Data were analyzed from February 1, through May 1, 2019.

MAIN OUTCOMES AND MEASURES:
Baseline group comparisons used (1) clinical trajectory; (2) cognitive screening scales; (3) serum neurofilament light chain (NF-L) levels; (4) TRIM11, ApoE, and MAPT genotypes; and (5) volumetric magnetic resonance imaging measures.

RESULTS:
A total of 222 patients with APS (101 with PSP, 55 with MSA, 40 with CBS, and 26 indeterminate) were recruited (129 [58.1%] male; mean [SD] age at recruitment, 68.3 [8.7] years). Age-matched control participants (n = 76) and patients with PD (n = 1967) were included for comparison. Concordance between the antemortem clinical and pathologic diagnoses was achieved in 12 of 13 patients with PSP and CBS (92.3%) undergoing postmortem evaluation. Applying the Movement Disorder Society PSP diagnostic criteria almost doubled the number of patients diagnosed with PSP from 58 to 101. Forty-nine of 101 patients with reclassified PSP (48.5%) did not have the classic PSP-RS subtype. Patients in the PSP-subcortical group had a longer diagnostic latency and a more benign clinical trajectory than those in PSP-RS and PSP-cortical groups. The PSP-subcortical group was distinguished from PSP-cortical and PSP-RS groups by cortical volumetric magnetic resonance imaging measures (area under the curve [AUC], 0.84-0.89), cognitive profile (AUC, 0.80-0.83), serum NF-L level (AUC, 0.75-0.83), and TRIM11 rs564309 genotype. Midbrain atrophy was a common feature of all PSP groups. Eight of 17 patients with CBS (47.1%) undergoing cerebrospinal fluid analysis were identified as having the CBS-AD subtype. Patients in the CBS-AD group had a longer diagnostic latency, relatively benign clinical trajectory, greater cognitive impairment, and higher APOE-ε4 allele frequency than those in the CBS-non-AD group (AUC, 0.80-0.87; P < .05). Serum NF-L levels distinguished PD from all PSP and CBS cases combined (AUC, 0.80; P < .05).

CONCLUSIONS AND RELEVANCE:
These findings suggest that studies focusing on the PSP-RS subtype are likely to miss a large number of patients with underlying PSP tau pathology. Analysis of cerebrospinal fluid defined a distinct CBS-AD subtype. The PSP and CBS subtypes have distinct characteristics that may enhance their early diagnosis.

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Audit of Brivaracetam in a Secondary Level Epilepsy Service (2019)

Type of publication:
Poster presentation

Author(s):
Rowe, J., Youssef, C., Tittensor, P., Manfredonia, F., *Smyth, C., Doherty, C.

Citation:
Poster presentation at ILAE British Branch Annual Scientific Meeting, 2-4 October 2019, Birmingham

Abstract:
A multicentre audit of the use Brivaracetam was carried out. Data were collated from 3 sites, The Royal Wolverhampton NHS Trust, Shrewsbury and Telford Hospitals NHS Trust and Walsall Healthcare NHS Trust Brivaracetam has shown efficacy and good tolerability and our experience suggests that it is a suitable add-on treatment for patients with refractory focal epilepsy. The very low rate of discontinuation for mood or behaviour reasons, particularly in the ID patients, indicates that it has the potential to be a positive choice for people with ID where issues have been noted on other medications, most notably Levetiracetam.

An audit of the Shrewsbury and Telford two week wait CNS malignancy pathway referrals over six months (2015)

Type of publication:
Poster presentation

Author(s):
*Metcalfe R, *Bowen J

Citation:
West Midlands Regional Neuroscience Meeting, 13 Nov 2015

Abstract:

An audit of the Shrewsbury and Telford two week wait CNS malignancy pathway referrals
over six months. By Metcalfe R*, Bowen J**
*Final year medical student, Keele University Medical School.
**Consultant Neurologist, Shrewsbury and Telford Hospital NHS trust (SaTH).
Word Count: 232 words.

Introduction:

  • The overall incidence of brain tumours in the U.K. is around 7/100,001
  • To promote early diagnosis a fast track “2 week wait” pathway exists for prompt diagnosis and initiation of management of brain/CNS tumours
  • In SaTH standardised suspected CNS malignancy referral proformas2 are faxed to meet 2 week targets appointments

Aim:

To undertake an audit to address the following:

  • Did referrals adhere to proforma criteria?
  • What proportion was seen within two weeks?
  • Is the process fit for purpose?

Methodology:

  • Case note review of all patients referred via the two week CNS Cancer pathway over a sixth month period from 1st July 2014 to 1st January 2015

Results:

  • Over the 6 months >98 % (120/122) referred via the two week wait pathway fulfilled the
    criteria on the proforma
  • Only 5.7% (7/122) were not seen within two weeks
  • 2 patients were diagnosed with brain metastases
  • No patients were diagnosed with a primary brain tumour

Conclusions:

  • Despite adherence of over 98% no case of primary brain tumour was detected over the six month period and 2 (1.6%) of patients referred had brain metastases
  • The current system is not effective at picking up brain tumours

Suggestions:

  • These results will be shared with local primary care groups and the referral criteria refined
  • A reaudit to assess impact of changes will be undertaken

References:
1. McKinney PA. J Neurol Neurosurg Psychiatry 2004;75:ii12-ii17
2. Shrewsbury and Telford Hospital NHS trust. Brain and CNS Cancer Two Week Wait
Referral Proforma. [internet] 2012 [Cited 6th October 2015] Available from:
www.sath.nhs.uk/Library/Documents/gpconnect/gpinfo/Brain%20and%20CNS
%20Cancer%20TWW%20Referral%20Proforma%20_V1_.pdf