Case 16 - Brain Injury

Case 16 - Brain Injury

1. Cellular Responses to Brain Injury

   • Nerve Injury
     • Glial Scar Formation
       • 1. Blood borne monocytes & macrophages invade injury site as BBB breached
       • 2. Microglia multiply & activate to remove cellular debris
       • 3. From 24h, oligodendrocyte precursors divide & hypertrophy (astrocytes follow after another 24h)
       • 4. Astrocyte process link together to surround lesion to recreate BBB
       • 5. Meningeal like cells invade lesion cavity --> Plug
       • 6. Cytokines control glial scar formation
     • Diffuse Axonal Injury
       • Torsion & impact on neuron leading to long term injury & cell death
       • Associated with coup & contracoup --> Sometimes misdiagnosed
       • Severs DAI leads to unconsciousness
       • Markers of DAI detect amyloid build up 2-3h after injury
       • Petechial haemorrhages can occur at interface of white/grey matter
       • Can lead to transneuronal degeneration --> Enlargement of ventricles due to white matter haemorrhages
   • Nerve Regeneration
     • PNS Regeneration
       • Schwann cells de-differentiate & stay within basal lamina of previous axon
       • Macrophages invade & secrete factors to promote Schwann cell migration & axon growth
       • Axons grown 1mm/day
     • PNS Degeneration
       • Triggered by extra & Intracellular Ca2+ entering cytosol activating calpain --> Breaks down cytoskeleton
       • Schwann cells phagocytose debris but also secrete trophic factors --> Promote axonal growth (for 1-2 months)
       • Enzymes break down neutron from distal end --> Proximal end (from cell body)
     • CNS - No Regeneration
       • Blocked by glial scar formation & release of inhibitory molecules by glial cells & macrophages
   • Microanatomy
     • Neurons & Glial cells
       • Most neuronal cell division ceases few weeks after birth
       • Glial cells remain ability to divide throughout life in response to damage
       • Tumours therefore consist mainly of glial & meningeal cells
       • Microglia act like macrophages in response to infection
     • Astrocytes
       • Control extracellular ion conc. particularly K+
       • Deactivate some transmitters (particularly glutamate in excitotoxicity)
   • Cell Death
     • Apoptosis: Cell breaks up into membrane bound apoptotic bodies containing infarct organelles
       • 1. Loss of trophic survival factors e.g. BDNF, NGF, TNF
       • 2. This is orchestrated by proteolytic enzymes (caspases) & DNAases
       • 3. Resulting apoptotic bodies phagocytosed
       • No inflammatory response, but may be triggered by injury
     • Necrosis: Cell ruptures leading to inflammatory in tissue which can lead to further damage
   • Excitotoxicity
     • Glutamate Recycling
       • If neurons ruptured or if astrocyte metabolism compromised, levels of glutamate can rise
       • Glutamate converted back to glutamine or into GABA
       • Deactivated by uptake or neurocyte intake
     • Cellular consequences
       • Na+ Ca2+ accumulation as result of NMDA & AMPA receptor function
       • Rises in levels of Ca2+ & Na+ --> Osmotic swelling & cell rupture
       • Rise in Ca2+ can activate necrotic signals
   • Oxidative Stress
     • NB: Can occur both in injury & neurodegenerative disease
     • Normal cellular respiraton produced ROS, excitoxicity can produce RNS
     • Large amounts of Ca2+ --> Abnormal level of ROS production
     • Vitamins C, E, superoxide dismutase (SOD) & glutathione peroxidase scavenge & protect against damage (deficient in MND)

2. Neurosurgical & Cranial Emergencies

   • Raised Intracranial Pressure
     • Symptoms
       • Headaches, nausea & vomiting
       • Altered consciousness
       • Cranial Nerve Palsies due to pressure on upper brainstem e.g. Ophthalmoparesis (CNIII, IV - most susceptible as longest route - & VI)
       • Vital Signs: Cushing's Triad = Increased systolic bp, bradycardia & abnormal respiratory pattern
       • Papilloedema
     • Herniation
       • Uncal Herniation (A)
         • Compression of CNIII --> Blown ipsilateral pupil
         • Coma occurs from midbrain compression
       • Central Herniation (B)
         • Symmetrical Movement of thalamic structures
         • Midbrain Compression
       • Transfalcine Herniation (C)
         • Displacement of cingulate gyrus under fall cerebri & across midline
       • Foraminal Herniation (D)
         • Cerebellum --> Foramen magnum
         • Compression of medulla & respiratory arrest
   • Haemorrhages
     • Types
       • Intracranial haemorrhage
         • Subarachnoid Haemorrhage: Blood within subarachnoid space
           • Often caused by aneurysms - e.g. Berry (Circle of Willis)
           • CSF yellow within 12 hours
         • Intracerebral: Blood in parenchyma
         • Cerebellar: Can cause coma & acute hydrocephalus
         • Intraventricular: Blood in ventricular system, often --> obstructive hydrocephalus
       • Extracranial haemorrhage
         • Extradural: Haematoma forms between skull & outer layer of dura
           • Often due to fracture of squamous temporal bone --> Damage to middle meningeal artery
           • Midline shift present which decreases size of ventricles
           • Can form due to venous blood - torn sinus
         • Subdural haematoma: Collection of blood between dura & arachnoid mater of meninges
           • Due to stretching & tearing of bridging cortical veins as cross subdural space to drain
           • Concave lesion towards brain
     • Causes
       • Cerebral aneurysms
       • Arteriovenous malformation
       • Hypertension
       • Anti-Coagulants
       • Drug Abuse
   • Types of traumatic brain injury
     • Penetrative brain injury
     • Skull impact - brain contusion
       • Coup & Contracoup (e.g. Whiplash)
       • Contusion - Veins running between brain & sinuses rupture --> Slow subdural haemorrhage
     • Compression of brain tissue due to:
       • Haemorrhage
         • E.g. Uncal herniation when raised ICP forces uncus to obstruct midbrain
       • Depressed skull fracture
       • Raised intracranial pressure
     • Infection e.g. meningitis
     • Brain ischaemia (loss of blood flow)
       • Brainstem Stroke
         • e.g. Basilar artery --> Reticular formation of pons
         • Vertebral artery & Basilar artery stroke mortality = 85%
         • Coma due to damage to Ascending Reticular Activation System (controls consciousness) in core of brainstem
       • Occlusion of PICA
         • Contralateral loss of body pain & temperature (Spinothalamic tract)
         • Ipsilateral loss of facial pain & temperature (trigeminal tract)
         • Dysphasia, hoarseness, loss of gag reflex (nucleus ambiguous & roots of CNIX & X)
         • Ipsilateral Horner's Syndrome (DLF)
         • Vertigo, double vision (vestibular nuclei)
         • Ipsilateral ataxia (spinocerebellar tract)
   • Hydrocephalus
     • Management: Ventriculo-peritoneal shunt or endoscopic third ventriclostomy
     • Obstruction of CSF within ventricular system or SA space --> Rise in fluid
     • Can cause papilloedema, headaches, dizziness
   • Spinal Emergencies
     • Cauda Equina Syndrome
       • Acute loss of neurological function of nerve roots below L1/2
       • Causes: Acute prolapsed disc & herniated lumbar disc
       • Signs: LMN signs, urinary incontinence, loss of anal tine, absent reflexes
     • Acute Spinal Cord Compression
       • Signs: UMN, Location specific pain, limb deficit, sensory loss & sphincter incontinence
       • Causes: Disc herniation, SD/ED haematoma, SD/ED empyema, tumour, fracture

3. Brain Anatomy

   • Cerebrospinal Fluid
     • Detection
       • Colourless & Odourless
       • Contains glucose (test with dipstick & then formally)
       • 'Halo' sign with blood
       • Beta-2-transferrin only in CSF
     • Production & Circulation
       • 1. Produced in choroid plexus of lateral ventricle
       • 2. Flows through interventricular foramen into 3rd ventricle
       • 3. Flows via cerebral aqueduct into 4th ventricle
       • 4. Leaves ventricular system through apertures of 4th ventricle
       • 5. Enters sub-arachnoid space
     • Reabsorption
       • 3. Here hydrostatic pressure in SA space > lumen of sinus due to greater colloid osmotic pressure of venous blood compared to CSF
         • 2. Site of reabsorption are arachnoid villi along sinuses
           • 1. Re-absorbed into venous system by passing into dural venous sinuses (e.g Superior sagittal sinus)
   • Radiological Anatomy
     • Spine X-Ray
       • Cranial Nerves
       • Radiological Neuroanatomy
       • Spine X-Ray
   • Anatomy of Neck
     • Carotid Sheath
       • Sympathetic Trunk located behind
       • Thyroid: Sup & Inf artery
     • Sternocleidomastoid
       • Landmark for JVP: Between sternal & clavicular head
       • Spinal Accessory nerve & C2/C3
     • Posterior Triangle
   • Airway
     • Epiglottis: Block trachea during feeding
     • Larynx: Open (Posterior cricoarytenoid muscle) & Close (Lateral cricocarytenoid)
   • Bones of Skull
     • Points of Weakness:
       • Pterion: 'H' shaped region between T, P, F & S bones - fracture lacerates meningeal artery (extradural haematoma)
       • Anterior, Middle & Posterior cranial fossa
   • Meninges

4. Infections of Brain

   • Meningitis
     • Inflammation of meninges
     • Triad of headache, fever & neck stiffness plus photophobia, altered LOC
     • Bacterial meningitis high mortality rate, fatal if unchecked BUT viral often self-limiting
     • Typical Organisms
       • Bacterial
         • Neisseria meningitides: Gram -ve, 'kissing' disease, NON BLANCHING, vancomycin
         • Streptococcal pneumoniae: Gram +ve, penicillin, triexone, dexamathasone
         • Listeria monocytogenes: Pregnancy, elderly & immune-compromised, ampicillin & vancomycin
         • Treatment: Broad spectrum (except neissera)
       • Viral
         • Enterovirus
         • No specific treatment
   • Chronic Meningitis
     • Fungal or TB (e.g. base of skull)
     • Common to find opthamoplegia in fungal
     • TB PCR ink stain for fungus
   • Encephalitis
     • Viral inflammation of brain tissue (can be autoimmune)
     • Presents with: Headache, fever plus cortical signs (cortical involvement - personality, seizure)
     • Causes: Herpes simplex (common), CMV, EBV, varicella zoster, HIV (direct), enterovirus & measles
     • Investigations: CSF analysis (similar to meningitis) - Antigen testing e.g. HSV PCR & HIV PCR
       • MRI, EEG & CT
     • Treatment: Antivirals, acyclovir, valaciclovir, ganciclovir etc. & HAART PLUS vaccination
   • Unusual infections
     • Abscess/emphyma
       • Local infection that spreads intracranially (e.g. mastoiditis)
       • Investigation: Contrast CT/MRI, locate source of infection, treatment (often gram +ve bacteria)
     • Rabies
       • Lyssavirusses spread from any warm blooded vertebrate
       • Universally fatal, 1 month incubation needed
       • Detected by: Fluorescent antibody test & negri bodies on biopsy
     • Cysticercosis: Parasitic (Taenia solium - COMMONEST CAUSE OF EPILEPSY)
     • Neurosyphilis: Manifestation of tertiary syphillis, differing latency according to structure affected = penicillin
     • Prion disease: Neurodegenerative

5. Management

   • Assessment of Unconscious Patient
     • Consciousness
       • 1. Conscious: Fully aware & interacting with environment
       • 2. Drowsy: Drifting but able to be roused
       • 3. Stupor: Able to be roused but slip back
       • 4. Coma: Prolonged consciousness e.g. sleep from which one cannot be aroused
         • a) Without neurological signs
         • b) With signs e.g. bleed, tumour
         • c) Meningitic syndrome --> Stiffness & SAH
       • 5. Vegetative state: Awake but non-responsive
     • Anatomy
       • Unconsciousness is disorder of: Reticular activating system (Diencephalon, midbrain & rostral pons = reticular formation), Thalamus & Cerebral Hemispheres
       • Lesions relate to whether supratentorium or infratentorium
       • Skull: Fixed area as non-flexible (brain, CSF & blood), can only compress it to a degree
         • According to Monro-Kellie Doctrine: Change in one results in compensation
     • Assessment
       • Collateral History
         • Why found?
         • How long for?
         • Abnormal health leading up to fall?
           • e.g. encephalitis starts like flu
       • Conscious level
         • GCS, FOUR & AVPU
       • Eyes
         • Vertical nystagmus --> bilateral pontine damage
         • Corneal reflex
           • High up lesion (CNV) - None on either side
           • Lesion after midline (CNVII) - No direct, present consensual
         • Doll's Eyes: Roving & opposite direction rolling = brainstem damage
       • Brainstem reflexes
         • Vestibular response: E.g. Caloric testing (normal = towards cold) - detects location of brainstem injury
         • Gag reflex - coughing on suction
       • Tone & reflexes
         • Hypertonia = Established cortical/cervical spine damage
         • Flaccid paralysis in acute SC injury
       • General examination
         • Resp: apneustic breathing
         • ECG: Fluid overload & MI
         • Dermatological: Rash = DIC, track marks from IVDU
   • Spinal Injury
     • Cauda Equina Syndrome
       • Urgent MRI, Urgent referral to surgeon for lumbar decompression & discectomy
     • Cord Compression
       • Urgent decompression, stabilisation, steroids (in metastases) NOT trauma
   • Acute Brain Injury
     • Haematoma
       • Epidural Haematoma
         • E.g. Male, 30yrs, Injury to head, 2hr later deterioration with LoC, headache, vomiting & CNIII palsy
           • Admit, bloods, mannitol (osmotic diuretic for raised ICP)
           • Craniotomy for evacuation of haematoma
       • Subdural Haematoma
         • More extensive surgery
     • Haemorrhage
       • E.g. Male 55yrs, SO headache, nausea, brief LoC, neck stiffness
         • Bed rest, IV fluids, nimodipine (vasospasm), analgesics
       • Control HT & investigate cause

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