Neurological Disorders

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Neurological Disorders
Tumors - 24,000/yr Cerebrovascular Accidents -
500,000/yr Seizure Disorders - 2,000,000 in
US Traumatic Brain Injury - 1/1000 - 50,000
die/yr Infectious Diseases Degenerative
Disorders
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Types of Tumors
Malignant - cancerous infiltrating Benign -
noninfiltrating (encapsulated) Gliomas
(60) Glioblastoma - worst Astrocytoma
(70) (same etiology - just severity
really) Meningioma Metastatic carcinoma
(35) - skin, lung, breast, prostrate
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Treatment - neuro-oncology
Surgery craniotomy Radiosurgery (radiation
treatment) - goal - tumor only Chemotherapy
(less in brain cases) - drugs taken up my tumor
cells - blood-brain barrier
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Neurological Disorders
Cerebrovascular Accidents Trauma Infectious
Diseases Degenerative Disorders
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Stroke - cerebrovascular accidents
Ischemic (80) thrombus - 50 embolus -
30 TIA infarct Hemorrhage
(20) intracerebral - 14 subarachnoid -
6 hypertension, aneurism, AVM
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Stroke - cerebrovascular accidents

• The glutamate cascade (ischemic cascade)
• -anoxia - starving or flood with blood
• - release glutamate
• - stimululate - calcium enters
• mitochondria - iron released??
• oxygen free-radicals
• Treatments - prevent or in acute phase
• antithrombotic - aspirin
• anticoagulants - warfarin, heparin
• thrombolytic - tissue plasminogen activator
  (t-PA)
• calcium antagonist
• glutamate antagonist

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Psychoactive Drugs
Psychedelics Phencyclidine - PCP or angel
dust - ketamine is similar - analgesic-
amnesiac- anesthestic (powerful) - NMDA
receptor - antagonist very good amnesiac -
prevent Ca influx and cell death from stroke?
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3401
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Rostral
Olfactory bulb
Anterior cerebral artery
Optic nerves (cut off)
Internal carotid artery
Middle cerebral artery
Temporal lobe
End of temporal lobe removed
Pituitary gland
Mammiliary bodies
Pons
Posterior cerebral artery
Medulla
Basilar artery
Cerebellum
Vertebral artery
caudal
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3402
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Each of the three major arteries of the cerebral
hemispheres- the anterior, middle, and posterior-
provides blood to a different region of the
cerebrum.
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3403
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3416
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3417 - ischemic infarct Mid Cerebral - 24hr, 72hr
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3418 - cerebellar
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3419 - hemorrhage - basal ganglia
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3423 - left AVM
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3424 - AVM - acute, 2yrs
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3425 - AVM
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3426 - hypertensive - excess water watershed
lesions- eclampsia like
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34N27
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34N28 - thrombophlebitis
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Atropine Injectors
Why is this relevant? (war, nerve
gas??) Atropine - anticholineric - blocks Ach
receptors - competitive inhibitor - more
muscarinic than nicotinic Counters Nerve Gases -
Sarin, Soman, VX - irreversible AchE inhibitors
- organophosphates (1800s) - like malathion -
insects (mammals inactivate the drug)
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Atropine Injectors
Nerve Gas - Ach accumulates - autonomic
(parasym) - all faucets on - somatic - twitch
contractions, weakness - brain - anxiety,
confusion, ataxia, seizures Death - continual
depolarization of diaphram - die due to
respiratory failure - also cardiac arrest -
Pralidoxime treatment - fixes AchE
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Seizure Disorders (epilepsy)
Sudden excessive activity of cerebral neurons
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Seizure Disorders
Generalized Tonic-clonic (grand mal) Absence
(petit mal) Atonic (loss of muscle
tone) Partial Simple (normal consciousness) lo
calized (partial) motor Motor
seizure Sensory Psychic Autonomic Complex
(altered conciousness) automatisms
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Seizure Disorders
Generalized Tonic-clonic (grand mal) Absence
(petit mal) Atonic (loss of muscle
tone) Partial Simple (normal consciousness) lo
calized (partial) motor Motor
seizure Sensory Psychic Autonomic Complex
(altered conciousness)
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Seizure Disorders
Generalized Tonic-clonic (grand mal) Absence
(petit mal) Atonic (loss of muscle
tone) Partial Simple (normal consciousness) lo
calized (partial) motor Motor
seizure Sensory Psychic Autonomic Complex
(altered conciousness) automatisms
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Infantile Spasms - West Syndrome - start before
12mo - cease 4y - arms flap , body bends
forward
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Seizure Disorders
Daiagnosis brain imaging (MRI) electrical
recording (EEG) Treatment Variety of
Drugs Anticonvulsants (Dilantin,
Tegretol) Surgery - map - record - cut
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Neurological Disorders
Tumors - 24,000/yr Cerebrovascular Accidents -
500,000/yr Seizure Disorders - 2,000,000 in
US Traumatic Brain Injury - 1/1000 - 50,000
die/yr Degenerative Disorders Infectious
Diseases
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Trauma
Lots of causes Lots of effects - damage -
contusion - hemorrhage
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3501
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3504
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3505
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3506 0 subdural hematoma
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3507 - chronic subdural hematoma
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3508 - chronic subdural hematoma - frontal lobes
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Degenerative Diseases
Parkinsons Disease - 500,000 folks degeneration
of dopamine neurons from S.N. -
pesticides/toxins - destroy mitochondrial
complex 1 (enzyme) - rotenone - affects all,
kills dopamine neurons (rats) Huntingtons
Chorea (heredity - chromosome 4) - 30,000 -
degeneration of putatmen and caudate nucleus
(N.O. ?) - lose inhibitory control Multiple
Sclerosis - 350,000 - autoimmune demyelinating
disease Alzheimers Disease (linked to Ach
neurons) - dementia - neuritic plaques (beta
amyloid) neurofibrillary tangles
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Beta amyloid plaque and neurofibrillary tangles
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Multiple sclerosis - sclerotic plaques in white
matter
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Infectious Diseases
Encephalitis Viral infection Arboviruses
(insects) Herpes Simplex poliomyelitis Rabies
AIDS - toxoplamosis - protozoa parasite Prion
Diseases (proteinaceous infectious
partic.) Spongiform Encephalopathies Creutzfe
ldt-Jakob Kuru Meningitis viral - usually not
bad bacterial - can be bad - Hib vacine in kids
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3302 - herpes encephalitis - left insula and
temporal
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33N23 - HIV
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Animal Models of Human Neuropsychological
Disease Animals - easier way to study Kindling
Model - Epilepsy - repeated elect stim to
amygdala - long lived changes - distributed,
not massed, stimulation Transagenic Mice - AD -
develop plaques (but not tangles) MPTP - for
parkinsons - metabolized into MPP - kills DA
neurons Deprenyl blocks it
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• Neural Degeneration
• anterograde - distal part
• proximal - towards cell body
• Neural Regeneration
• not great
• a little in PNS - guided by Schwann cells
• - how much guidance determines outcome
• Neural Reorganization
• yes, it happens, big area of work
• mostly sensory motor
• - even new neurons - hippocampus

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Recovery after brain damage - neural function -
not a lot really - reduced edema swelling -
when cells die they are gone - learn new
strategies - e.g., new path to old end
point - cognitive reserve
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Neuroplasticity Treatment - prevent
damage - clear the blockage - block Ca
uptake - other proteins involved - promote
regeneration - kill oligodendrocytes -
promote Schwann cells - neurotransplantation -
usually dopamine cells - Parkinsons - stem
cells - pluripotent