Punch drunk syndrome, also known as dementia pugilistica or chronic traumatic encephalopathy, is a neurodegenerative disease that affects athletes who have suffered repeated concussions, especially boxers. It is characterized by tau protein deposits in the brain and symptoms that include mood changes, behavioral issues, cognitive decline, and motor problems. While symptoms may not appear for years or decades after head impacts, it eventually leads to full-blown dementia. The neuropathology shows atrophy, neuronal loss, tau deposits, and in some cases amyloid plaques or TDP-43 inclusions. Genetic factors like the ApoE4 allele may increase risk. Boxers tend to have more severe and longer lasting symptoms than other

1. PUNCH DRUNK
BY
FAIZ AHMAD
JR 1, FORENSIC MEDICINE
JNMCH ALIGARH

2. DEFINITION
Punch-drunk or punch-drunk syndrome;
 is a neurodegenerative disease with features of dementia that
may affect amateur or professional boxers, wrestlers as well as
athletes in other sports who suffer concussions.
 A variant of chronic traumatic encephalopathy(CTE) it is also
called;
 Dementia pugilistica,
 Chronic boxer's encephalopathy,
 Traumatic boxer’s encephalopathy,
 Boxer's dementia,
 Chronic traumatic brain injury associated with
boxing (CTBI-B),
 Punch-drunk syndrome.

3.  Progressive neurodegenerative disease, distinct from
Alzheimer’s. –Tauopathy
 Symptoms begin months or years after concussions
and continue to worsen.
 Eventually leads to full-blown dementia.
 Perhaps the only fully preventable cause of dementia

4. Dementia Pugilistica
First described in boxers by Martland in 1928
–Martland HS: Punch drunk. JAMA 91:1103–
1107, 1928.
Harrison S. Martland
(1883-1954)
First full time paid pathologist
Newark city Hospital, 1909-1927
Chief Medical examiner Essex
county
23 cases reported to him by a single
boxing promoter
5 cases ‘personally examined’
1 case with clinical details

5.  Martland, in 19281, first brought the expression
“punch drunk syndrome” to medical literature,
 Hitherto used by the lay public and boxing fans to name the
condition that some boxers develop during or after their
fighting career.
 The syndrome consisted of extrapyramidal and cerebellar signs
and symptoms, associated or not, with cognitive and behavioral
abnormalities.

6.  In 1937, the designation “dementia pugilistica” was
proposed.
 Critchley, in 19573, named it “chronic progressive
encephalopathy of the boxer”, being more descriptive in
that it represents the long term cumulative effect of
repetitive head trauma.
 However, the label dementia pugilistica has been more
frequently used.

7. Clinical presentation
 Clinical symptoms of DP
generally present years or
decades after exposure to
trauma.
 Although there are some
symptom overlaps between
the acute concussive injury
and the later-life
neurodegenerative process of
CTE.

8.  CTE indistinct from the
acute concussion or post-
concussion sequelae.
 A history of repetitive brain
trauma is thought to be
necessary to cause CTE.

9.  All neuropathologically confirmed
cases of CTE to date have a
history of repetitive brain trauma.
 CTE symptoms are not just the
cumulative effects of this process.

10.  There is no clear relationship between
prolonged acute concussion symptoms
(e.g, post concussion syndrome) and
the pathology of CTE.
 CTE presents clinically with
symptoms in one or more of four
possible domains;

11. MOOD; Depression,Irritability,Hopelessness.
BEHAVIOR; Impulsivity,Explosivity,Aggression,
Premorbid personality traits, Suspiciousness, Paranoia,
Childishness,
Hypersexuality,Restlessness,Inappropriateness,and
Explosive outbursts of aggression.

12. COGNITION; Memory impairment, Executive
dysfunction, Information processing, Attention,
Concentration, Sequencing abilities, Judgment,
Reasoning, Future planning, Organization and in severe
cases Dementia.
MOTOR SYMPTOM; parkinsonism, ataxia, and
dysarthria, dysphagia, and ocular abnormalities, such as
ptosis.

13. In addition, chronic headache is also experienced in some
cases
Boxers with DP can also exhibit symptoms resembling other
degenerative disorders, including: Parkinsonism, Dementia,
Alzheimer’s disease, Wernicke-Korsakoff syndrome, and
Kluver-Bucy syndrome.

14. Two distinct clinical presentations of CTE have been
described in a recent study by Stern et al.
 The first type initially presents with mood and behavioural
symptoms earlier in life (mean age approximately35) and
cognitive symptoms later in the disease course.
 The second clinical presentation begins with cognitive
impairment later in life (mean age approximately 60) which
may progress to include mood and behavioural symptoms.

15. Corsellis, Bruton, and Freeman-Browne described 3 stages of
clinical deterioration;
 The first stage is characterized by affective disturbances and
psychotic symptoms. Social instability, erratic behavior,
memory loss,
 Initial symptoms of Parkinson disease appear during the
second stage.
 The third stage consists of cognitive dysfunction, dementia
and is accompanied by full-blown Parkinsonism, as well as
speech and gait abnormalities.

16. Neuropathologic characteristics
Gross Pathology
1. A reduction in brain
weight.
2. Enlargement of the
lateral and third
ventricles.
3. Thinning of the corpus
callosum.
Brai nweight: 156 0grams Brainw eight:
1450g ms
10 years of professional football
Death in his 80s with dementia

17. 4.Cavum septum pellucidum
with fenestrations.
5.Scarring and neuronal loss of
the cerebellar tonsils.
6.Atrophy of the frontal
lobe,temporal lobe,
parietal lobe, and less
frequently, occipital lobe.
Cavum septum pellucidum

18. 7. With increasing severity of the
disease, atrophy of the
hippocampus, entorhinal cortex
and amygdala,olfactory bulbs,
thalamus, mammillary bodies,
brainstem and cerebellum,
8. Pallor of the substantia nigra and
locus ceruleus and thinning of
the corpus callosum.
Marked medial temporala trophy

19. Microscopic Pathology
Neuronal Loss;
1. Neuronal loss and gliosis seen in
the hippocampus, substantia
nigra and cerebral cortex.
2. Neuronal loss and gliosis
accompanyed by neurofibrillary
degeneration,and are more in the
hippocampus, subiculum, the
entorhinal cortex and amygdala.
Cerebral cortex –primarily
the frontal and temporal
lobes

20. 3.In advanced, neuronal loss is also
found in the subcallosal and
insular cortex ,frontal and
temporal cortex.
4.Other areas of neuronal loss and
gliosis include the mammillary
bodies, medial thalamus,
substantia nigra, locus ceruleus
and nucleus accumbens.
Medial temporal lobe –amygdala,
hippocampus, entorhinal
cortexFrontal

21. Tau Deposition
1. Hyperphosphorylated tau
(ptau)protein as neurofibrillary
tangles (NFT) , astrocytic
tangles, and dot-like,spindle-
shaped neuropil neurites (NNs)
are common in the dorsolateral
frontal, subcallosal, insular,
temporal, dorsolateral parietal,
and inferior occipital cortic
Tau immunoreactive NFTs

22.  The tau-immunoreactive
neurofibrillary pathology is
characteristically irregular in
distribution with multifocal
patches of dense NFTs in the
superficial cortical layers,
Tau immunoreactive NFTs

23. 3.The irregularand perivascular
nature of the p-tau neurofibrillary
tangles, subpial and periventricular
involvement are unique features of
the disease that distinguish it from
other tauopathies.
4.Early stages show sparse TDP-43
positive neurites in cortex,medial
temporal lobe, and brainstem.
Medulla Cord
Pons

24. 5.Late-stage pathology presents withTDP-43 intraneuronal and
intraglial inclusions in the frontal subcorticalwhite matter and
fornix, brainstem, and medial temporal lobe.
β-Amyloid Deposition;
Few case shows diffuse Aβ plaques in the frontal, parietal and
temporal cortex, and sparse neuritic plaque.

25. death at age 45 years: depression, poor decision
making, substance abuse
Orbital frontal Hippocampus Temporal Amygdala
Aß: rare diffuse plaques

26. High school football player- Death at age 18.
Cognitively intact. Focal evidence of perivascular
tau
Tau immunohistochemistry
No Aß
John Doe
18 yrs
HS football
Tau positive
Neurofibrillary tangles
Frontal cortex
Tau positive
Neurofibrillary tangles
Insula cortex

27. CTE in Boxers
 Boxing is the most frequent sport associated with CTE and
disease duration is the longest in boxers, with case reports of
individuals living for 33, 34, 38, 41 and 46 years with
smouldering, yet symptomatic disease .
 Differences in the nature of exposure could account for
differences in presentation.

28.  Boxers experience proportionally more rotational acceleration than
in football.
 Computational modeling of boxing impacts suggests that stress in
boxing impacts is greatest on midbrain structures,and midbrain
damage may account for the parkinsonian features found in CTE .
 Professional boxers exhibited significantly more motor symptoms
(eg, ataxia dysarthria) relative to football players.
 Boxers displayed more cerebellar scarring than football players.

29.  Football players, were younger at the time of death compared to boxers with
CTE.
 The duration of symptomatic illness was also shorter in the football players
compared to the boxers.
 In the football players, the most common symptoms were mood disorder
(mainly depression), memory loss, paranoia, and poor insight or judgment
,outbursts of anger or aggression etc,

30. MRI-STUDY
 No morphological lesions
seen on structural MRI.
 Reduced perfusion/activity
in dor so-lateral pre-frontal
cortex when athletes with
PCS performed working
memory task.

32. Genetic Risk and the Role of ApoE4
 ApoE4 genotyping association has been reported in cases of CTE,
 Five of the 10 cases of CTE carried at least one ApoE ε4 allele
(50%), and 1 was homozygous for ApoE ε4 .
 The percentage of ApoE ε4 carriers in the general population is 15%;
this suggests that the inheritance of an ApoE ε4 allele might be a risk
factor for the development of CTE.

33.  In acute TBI effects of head trauma are more severe in ApoE ε4-positive
individuals.
 Acute TBI induces Aβ deposition in 30% of people and a significant
proportion of these individuals are heterozygous for ApoE ε4.
 ApoE4 transgenic mice suffer greater mortality from TBI than ApoE ε3
mice . Furthermore, transgenic mice that express ApoE ε4 and overexpress
APP show greater Aβ deposition after experimental TBI.

34. Thanks