PUNCH DRUNK

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

DEFINITIONPunch-drunk orpunch-drunk syndrome; is a neurodegenerative disease with features of dementiathat 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 boxers encephalopathy,Boxer's dementia,Chronic traumatic brain injury associated with boxing(CTBI-B), Punch-drunk syndrome.

Progressive neurodegenerative disease, distinct from Alzheimers. TauopathySymptoms begin months or years after concussions and continue to worsen.Eventually leads to full-blown dementia.Perhaps the only fully preventable cause of dementia

Dementia Pugilistica

First described in boxers by Martland in 1928Martland HS: Punch drunk. JAMA 91:11031107, 1928.Harrison S. Martland(1883-1954)First full time paid pathologist Newark city Hospital, 1909-1927Chief Medical examiner Essex county23 cases reported to him by a singleboxing promoter5 cases personally examined1 case with clinical details

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.

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.

Clinical presentationClinical 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.

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

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.

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;

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

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.

In addition, chronic headache is also experienced in some casesBoxers with DP can also exhibit symptoms resembling other degenerative disorders, including: Parkinsonism, Dementia, Alzheimers disease, Wernicke-Korsakoff syndrome, and Kluver-Bucy syndrome.

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.

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.

Neuropathologic characteristicsGross PathologyA reduction in brain weight.Enlargement of the lateral and third ventricles.Thinning of the corpus callosum.

Brai nweight: 156 0grams Brainw eight: 1450g ms10 years of professional footballDeath in his 80s with dementia

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

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

Microscopic Pathology

Neuronal Loss;Neuronal loss and gliosis seen in the hippocampus, substantia nigra and cerebral cortex.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

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

Tau Deposition

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

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

Tau immunoreactive NFTs

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

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

death at age 45 years: depression, poor decision making, substance abuse

Orbital frontal Hippocampus Temporal Amygdala A: rare diffuse plaques

High school football player- Death at age 18. Cognitively intact. Focal evidence of perivascular tau

Tau immunohistochemistryNo AJohn Doe18 yrsHS footballTau positive Neurofibrillary tanglesFrontal cortexTau positiveNeurofibrillary tanglesInsula cortex

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.

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.

CTE in Football Players

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,

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.

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 4 allele (50%), and 1 was homozygous for ApoE 4 .The percentage of ApoE 4 carriers in the general population is 15%; this suggests that the inheritance of an ApoE 4 allele might be a risk factor for the development of CTE.

In acute TBI effects of head trauma are more severe in ApoE 4-positive individuals. Acute TBI induces A deposition in 30% of people and a significant proportion of these individuals are heterozygous for ApoE 4. ApoE4 transgenic mice suffer greater mortality from TBI than ApoE 3 mice . Furthermore, transgenic mice that express ApoE 4 and overexpress APP show greater A deposition after experimental TBI.

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