Table 1.
Boxing-related CTE over more representative reports in literature
| Authors / years | Type of study / patients | Main observations |
|---|---|---|
| Martland, 1928 | 23 cases of retired boxers (clinical details in the case-report of a 38 year-old retired professional boxer) | “Punch-drunk syndrome” (“the occurrence of the symptoms in almost 50% of fighters seems to be good evidence that some special brain injury due their occupation exist”) |
| Millspaugh, 1937 | - | “Dementia pugilistica” |
| Critchley, 1957 | 21 case reports of boxers (16 professional), at different stages of their sportive activity | Panel of possible boxing-related neuro-psychiatric injuries over the time (knock-out/amnesias → “Groggy state” → “Punch-drunk state”); “Chronic progressive encephalopathy” (cumulative brain damage) |
| Roberts, 1969 | Prospective study: randomly sampled 250 retired professional boxers (registered in British Boxing Council between 1929–1955) of which 224 formally studied (physical examinations, psychiatric interviews, neuropsychological assessment, EEG and pneumoencephalography) | Prevalence of clinically defined boxing-related CTE among British retired professional boxers in the percentage of the 17% |
| Corsellis et al., 1973 | Neuropathological examinations in 15 cases of retired boxers with CTE | Characteristic neuropathological findings: NFT spreaded diffusely through both the cerebral cortex and brain-stem, CSP with fenestrations, cerebellar and cerebral scarring and degeneration of the substantia nigra; absence of SP |
| Guterman and Smith, 1987 | Literature review (physiopathology of brain injury; neuropathological, clinical and neuroradiological aspects; analyson contributions of electrophysiological studies and other laboratory methods; questioning on safety of boxing) | Correlation between EEG abnormalities in boxers with encephalopathy (while present in approximately 60% of cases) and encephalopathy is low: role of EEG in prevention, but not in diagnosis |
| Roberts et al., 1990 | Neuropathological examinations of 20 CTE cases in ex-boxers (15 professionals and 5 amateurs, of which 14 cases from archival formalin-fixed material of original study of Corsellis et al., 1973) + 20 Alzheimer’s Disease cases + 20 cases-controls | At the immunocytochemical investigation, presence in all the DP cases of extensive β-amyloid deposits (diffuse SP) |
| Hof et al., 1992 | Neuropathological examinations of 3 cases of CTE (in 3 retired professional boxers) + 8 cases of AD | Association cortex of brains in DP demonstrates an inverse NFT distribution as compared to AD |
| Unterharnscheidt, 1995 I,II,III,IV,V | Literature review (neurological and neuropathological aspects) | Permanent brain damage in boxers (both professional and amateur) |
| Mendez, 1995 | Literature review of studies on 274 professional boxers (neurobiological, clinical, neuropsychological, diagnostic, and management aspects of boxing-related brain injuries) | Clinical expression of CTE may results in a spectrum (mild, non-progressive motor changes → DP). Safety’s measures and rehabilitation techniques do not eliminate risk of CTE |
| Jordan, 2000 | Literature review (clinical, diagnostic, neuropathological and treatments aspects) | Main risk factors for CTBI: increased exposure (i.e., duration of career, age of retirement, total number of bouts), poor performance, increased sparring, ApoE-ε4. Mainstay of treatment is prevention; medications used in AD and/or parkinsonism may be utilized |
| Moseley, 2000 | Literature review (significance analysis of structural and functional neuroimaging techniques) | Significant correlations between imaging abnormalities and clinical evidence of brain damage not attainable by most morphological studies; large informative data in functional imaging not yet available |
| Clausen, 2005 | Literature review on retired professional boxers and data analysis of active professional boxers (636 subjects since 1930s to present, in the U. K. and Australia) | Exposure in professional boxing (measured by bouts and length of career) has decreased significantly over the century → incidence of boxing related CTBI should diminish in the current era |
| McCrory et al., 2007 | Literature review (definition, pathophysiology, clinical assessment, epidemiological data and neuroanatomical/neuroradiological aspects) | Attempt of establishing clinical evidence basis for boxing-related CTE |
| Areza-Fegyveres et al., 2007 | Case report (a 61 year-old retired boxer, amateur for 14 years and professional for 3 years) | A case of DP diagnosed on neuroimaging and neuropathology data with practically undistinguishable clinical features from AD |
| Loosemore et al., 2008 | Review of observational studies on clinically defined boxing-related CTE (1950 to 2007) | There is no strong evidence to associate CTE with amateur boxing |
| Heilbronner et al., 2009 | Literature review (neuropsychological aspect and recommendations to improve safety standards) | Recommendation of a systematic monitoring of the neurocognitive status throughout a boxer’s career (baseline and serial neuropsychological assessments) |
| Nowak et al., 2009 | Case report and literature review (a retired world boxing champion; correlation of clinical features with histochemical and immunohistochemical changes) | Dementia in retired boxers could be exacerbated by others etiologic factors than those typical in DP (such as multiple cerebral infarcts and Wernicke-Korsakoff syndrome) |
| McKee et al., 2009 | Review of 48 cases of neuropathologically verified CTE recorded in literature (37 retired boxers) and clinical findings of 3 case reports (2 retired boxers) | CTE as a neuropathologically distinct slowing progressive tauopathy with a clear environmental etiology; hypothesis of interactions with the pathogenetic cascade of AD |
| Orrison et al., 2009 | Literature review on MRI findings and assessment of 100 unselected consecutive 1.5- and 3.0-Tesla MRI examinations of professional unarmed combatants (boxers and mixed martial arts fighters) | Literature-based checklist approach by high-field MRI showed that 76% of the unarmed combatants had at least one finding that may be associated with Traumatic Brain Injury: 59% hippocampal atrophy, 43% CSP, 32% dilated perivascular spaces, 29% diffuse axonal injuries, 24% cerebral atrophy, 19% increased lateral ventricular size, 14% pituitary gland atrophy; 5% arachnoid cysts and 2% contusions. Possible role in prevention of a systematic assessment |
| Handratta et al., 2010 | Case report (a retired professional boxer, 47-years-old, with double diagnoses of schizophrenia and CTBI) and literature review | Hypotheses about pathophysiology of neuroimaging findings and their relationship to neuropsychiatric symptoms |
| King et al., 2010 | Neuropathological examinations of 59 cases of a variety of neurodegenerative conditions (of which 3 cases of boxing-related CTE) | Peculiar pattern of abnormal expression of TDP-43 in the neocortex of boxing-related CTE cases |
| Omalu et al., 2010 | Clinical findings + neuropathological examinations of 5 cases of CTE in professional contact sports athletes | Suicidal and para-suicidal behaviors |
| McKee et al., 2010 | Clinical findings + neuropathological examinations of 12 cases of CTE, of whom 3 with MND (4 professional boxers) | TDP-43 proteinopathy in brain and spinal cord: clinical and pathological link between CTE, FTD and MND |
Abbreviations: AD: Alzheimer’s disease; CTBI: chronic traumatic brain injury; CSP: cavum septum pellucidum; CTE: chronic traumatic encephalopathy; DP: dementia pugilistica; FTD: frontotemporal dementia; MCI: minimal cognitive impairment; MND: motor neuron disease; MRI: magnetic resonance imaging; NFT: neurofibrillary tangles