title: Simulated surgical-type cerebral biopsies from post-mortem brains allows accurate neuropathological diagnoses in the majority of neurodegenerative disease groups.
abstract: BACKGROUND
  In theory, cerebral biopsies could provide the diagnosis in a significant proportion of patients with neurodegenerative diseases, however, there are considerable ethical barriers. Previous series of cerebral biopsies have shown variable diagnostic accuracy but have understandably suffered because of lack of post-mortem tissue with which to compare the diagnosis. To determine the accuracy of such biopsies in neurodegenerative disease we took small biopsy-sized samples of predominantly fresh post-mortem brain tissue from frontal and temporal lobes in 62 cases. These were processed as for a biopsy and stained for H&E, p62, tau, Aβ, α-synuclein, and TDP-43. The sections were assessed blind by 3 neuropathologists and the results compared with the final post-mortem diagnosis.
  
  
  RESULTS
  The agreement and sensitivity in most cases was good especially: controls; Alzheimer's disease (AD); multiple system atrophy (MSA); frontotemporal lobar degeneration with TDP-43 positive inclusions and/or motor neurone disease (FTLD-TDP/MND); Huntington's disease (HD); corticobasal degeneration (CBD) / microtubular associated protein tau mutation cases with CBD-like features (CBD/MAPT); and combined AD- Dementia with Lewy Bodies (AD-DLB) where the sensitivity on assessing both brain regions varied between 75-100%. There was poor sensitivity for progressive supranuclear palsy (PSP) and amyotrophic lateral sclerosis (ALS) (both 0%), but moderate sensitivity for pure DLB (60%). The temporal lobe assessment was marginally more accurate than the frontal lobe but these were only slightly worse than both combined.
  
  
  CONCLUSIONS
  The study shows that with certain caveats the cerebral biopsy in life should be a viable method of accurately diagnosing many neurodegenerative diseases.
authors.affiliation: Department of Clinical Neuropathology, Academic Neuroscience Building, Kings College Hospital, SE5 9RS Denmark Hill, London, England. andrewking@nhs.net.
authors.forename: Andrew
authors.initials: A
authors.lastname: King
authors.forename: Satomi
authors.initials: S
authors.lastname: Maekawa
authors.forename: Istvan
authors.initials: I
authors.lastname: Bodi
authors.forename: Claire
authors.initials: C
authors.lastname: Troakes
authors.forename: Olimpia
authors.initials: O
authors.lastname: Curran
authors.forename: Keyoumars
authors.initials: K
authors.lastname: Ashkan
authors.forename: Safa
authors.initials: S
authors.lastname: Al-Sarraj
mesh_terms: D001706:Biopsy / Q000379:methods*; D005625:Frontal Lobe / Q000473:pathology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000175:diagnosis* / Q000473:pathology*; D012680:Sensitivity and Specificity; D013702:Temporal Lobe / Q000473:pathology*; D016707:Tissue Fixation