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Psych Congress  

Progressive Limbic Anterograde Transneuronal Degeneration (LATND): a Neuropathological & Radiological Biomarker in TBI-induced CTE & Dementia

Authors  
William Torch, MD, MS
Sponsor  
NeuroDevelopmental & NeuroDiagnostic Ctr

In 1977, Torch et al [NEUROLOGY 27:1157-64] described LATND in a 64y.o. man who died after an 8yr progressive history of behavioral, sleep/autonomic disturbance, Alzheimers-like dementia[AD], associated with left temporal EEG slowing. Autopsy revealed an old left-hippocampal infarct with atrophy of the ipsilateral 1)fimbria/fornix[Fx], 2)mammillary-body[MB] & hypothalamus[HT], 3)mammillo-thalamic tract[MTT], anterior-thalamus[AT] & cingulum[C]. Clinical decline was attributed to 1o-2o -3o LATND. In determining child/adulthood prevalence, 128 published autopsy-cases of hippocampal injury in 4 major categories were reviewed: A)stroke[49 cases]; B)TBI/surgical[24 cases]; C)encephalitis[41 cases]; D) kernicturus[14 cases]. Miscellaneous cases included hippocampal-sclerosis; neoplasia; insulin-induced hypoglycemia; Atypical/Familial AD & Dementia-Infantilis. Using a graduated scale of microscopic-to- gross atrophy, rate & degree of LATND, and survival time (ST) were tabulated along with symptomatology in each case. Ipsilateral 1o-3o LATND was observed following uni- or bilateral: A)hippocampal stroke [14Lt:14Rt:12Lt/Rt]; B)boxing-induced TBI/CTE & hippocampal/fornix temporal-lobe surgery[1Lt:5Rt:18Lt/Rt]; C)encephalitis/vasculitis[3Lt:1Rt:37Lt/Rt];D)kernicterus/hypoxemia[14Lt/Rt]. LATND occurred in 65% of stroke-, 75% of TBI-, 37% of encephalitis-, 21% of kernicterus-affected hemispheres. Average-age of symptom-onset: infarction, 59y; TBI, 38y; encephalitis, 36y; kernicterus, 2.5d. Extent & degree of ipsilateral-LATND was linearly-related to ST, where mean ST was: TBI(13.3y)>infarction(3.9y)>encephalitis(3.4y)>kernicterus(2y). In stroke, rate of LATND progression was: Fx(4mos); MB(6-8mos); HT(1.5 y); MTT-AT(3y8 mos-5y), while in TBI: Fx(4-5 mo); MB(1-2.5y); HT(5-11y); MTT-AT(12-15 y). Advancing encephalopathy followed by dementia was seen in TBI(>5-10y); stroke(>2-4y); encephalitis(>3mo-2y; kernicteric-retardation(>1.5-2y), correlating with MTT-AT degeneration. While LATND-pathology is frequently overlooked at brain-cutting, recent literature-review of high-resolution CT/MRI/DTI/fMRI/PET/SPECT/MEG studies illustrates LATND as a potential radiological bio­marker for evolving dementia in hippocampal/amygdala-sensitive conditions, including contact sports (e.g. boxing-dementia-pugilistica, football, etc.), military-blast-TBI/CTE, child abuse/neglect-related TBI & cortisol-stress-induced-PTSD. LATND may hypothetically account for early "positive" hippocampal/amygdaloid encephalopathic-cognitive/affective/behavioral/psychotic symptoms, evolving into later "negative burned-out" stages in TBI/CTE and other various neuro-psychiatric dementias (e.g. AD/FTL/tau/prion schizophrenic-dementia-praecox, etc), reflecting initial diencephalic-deafferentation, denervationexcitation/hypersensitivity/dysinhibition, followed by progressive loss of neural-connectivity resulting limbic dementia.

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