• Alcoholism (with dietary deficiency in thiamine)
• Malignancy (gastric and esophageal cancers),
• Hyperemesis gravidarum
• Chronic dialysis
• Bariatric surgery

• Lateral rectus palsy, confabulation
• Mamillary bodies with petechial hemorrhages (along with various other areas)
• Rarefaction of the brain, vascular proliferation, macrophage infiltration; preservation of neuron (still reversible at this stage)
• Can be irreversible damage; mamillary bodies shrunken, sunken and brown (due to hemosiderin)

• Surgical excavation of mass
• Elevation of head (increase venous drainage)
• Keep head straight (avoid neck compression)
• Analgesia/sedation, osmotic diuresis (mannitol), CSF drainage

• Hyperventilation
• Monitor jugular and venous sat.
• Lobectomy or craniectomy
• Barbiturate coma
• Hypothermia, hyponatremia

• Mechanism of action
  • Binds to own site on GABA-a receptor (potentiates inhibition)
  • NMDA antagonist
  • Also binds to canniboid-1, opiate, glycine, ACh and 5-HT receptors
• Metabolism
  • Metabolized by alcohol dehydrogenase (zero-order kinetics) to acetylaldehyde (causes hang-over effect)
  • Microsomal ethanol-oxidizing system, catalase

• Withdrawal signs
  • Peaks 2-3 days after last drink
  • Typically done by day 5-10
  • Tachycardia, HTN, diaphoresis, tremor seizure (generalized)
  • Rare event = delirium (delirium tremens), discernible by EEG
  • Hallucinations (in America, often pink elephants)
• Clinical institute withdrawal assessment (CIWA)
  • Score >8, treat medically
  • Score >18, hospitalization

• Disulfiram
  • Inhibits acetylaldehyde dehydrogenase (increasing circulating acetylaldehyde)
  • Severe "hang-over" immediately upon drinking
  • Can cross-react with other alcohols (perfume, mouth-wash), with heterogenous adverse effect
• Naltrexone
  • Block opiate receptor, leading to decreased dopamine release from nucleus accumbens
  • Best results with family hx of alcoholism, with same sex parent affected
  • Get LFT's every 6 mo
• Acomprosate
  • Metaborotropic glutamate receptor antagonist (works as glutamate modulator)
  • Deals with compensatory glutamate upregulation that occurs with GABA potentiation

• Barbiturates control the degree of chloride channel at the GABA receptor. They are potentially fatal.

• Benzos bind to the GABA receptor itself, controlling the frequency of chloride channel opening. Not fatal by itself, but fatal with alcohol

• Mu (site for morphine), used in supraspinal analgesia; causes respiratory depression, constipation, sedation, euphoria, miosis
• Kappa, used for spinal anesthesia; causes sedation, dysphoria, psychomimetic
• Delta, multiple functions

Note: all G-coupled receptors

• Diarrhea, rhinorrhea, abdominal cramping, vomiting, malaise, dysphoria, myalgia
• Withdrawal is non-lethal, but addicts have lower tolerance for pain/discomfort due to diminished endorphin function

• Naltrexone
  • Long acting opiate blockade with an antagonist
  • Compliance is big problem, except for medical professionals
  • Blockade of endogenous opiates in these patients 
• Methadone
  • Long acting opiate blockade with an agonist
  • Typically given PO, QD
  • Can safely be on maintenance for years to prevent withdrawal and cravings
  • Tight federal regulation
  • Takes weeks to months to detox from it b/c long t ½
  • Ppl on methadone maintenance - More alert than general population!!
• Buprenorphine
  
  • Partial agonist
  • Mechanism of action: Opiate agonist up to a certain level of tolerance, then is an antagonist.
  • Ceiling effect, so can’t OD
  • Metabolized By cytochrome 450 3A4, so a lot of interaction potential (benzo, TCA, eryththromycin, nifedipine, HIV protease inhibitors).
  • No street value
• Suboxone
  
  • Buprenorphine + naloxone

1. The synthetics (meperidone, methodone, propoxyphene, fentanyl)
2. Miosis and constipation (users develop tolerance to euphoria; typically drug seek to avoid withdrawal)

Not linear; <8 is classified as severe traumatic brain injury; doesn't give complete picture

• Eye opening (spontaneously, in response to voice, pain, or none)
• Verbal response (oriented x3, semi-lucid sentences, inappropriate words, incomprehensible sounds, or none)
• Motor response (to command, localization of pain, withdraws from pain, flexion, extension, none)

1. Sub-acute combined degeneration (degeneration of the posterior cords), generally at the thoracic level, leading to parathesia and loss of proprioception.
2. Loss of myelin basic protein, limiting myelin maintenance
3. Vacuolization in spinal cords with macrophages in the area (otherwise, vacuolization = artifact)

1. Petechial hemorrhages in the brain (cherry red coloration) with massive edema
2. Headache, dizziness, impaired hearing and vision, confusion, convulsion, coma, cardio-respiratory failure
3. Globus pallidus (iron-rich), anterior vessels

TORCH

1. Toxoplasmosis
2. "Other"
3. Rubella
4. Cytomegalovirus
5. Herpes/HIV

1. Days 16-28
2. 1/500
3. Alpha fetoprotein

Absence or hypoplasia of the skull vault, typically incompatible with life >1 week. Due to failure in anterior neural fold formation. 

Area cerebrovasculosa present (mass of disorganiced tissue)

• Meningocele - sac containing meninges, but not spinal cord
• Myelomeningocele - sac containing meninges AND spinal cord
• Spina Bifida Occulta - malformed spinal arches, no herniation
• Congenital dermal sinus - connection between skin and subarachnoid space

Failure of the prosencephaly (forebrain) to form. No midline, one hemisphere.

Chromosome 13 and genes of the Sonic Hedgehog pathway (as well as cholesterol inhibitors, which modify SHH)

1. Lissencephaly, type I (due to failure in migration @ month 3-4)
2. Lessencephaly type II (cobblestone appearance)
3. Doublecortin (microtubule binding protein)

• Males - lissencephaly (smooth brain)
• Females - subcortical band hetertopias (double cortex)

• Dandy-Walker malformation
• Enlarged posterior fossa, a/hypoplasia of the cerebellar vermis, agenesis of corpus callosum, aqueductal stenosis
• Seen in lissencephaly type II

Damage to the circulation of the major arteries in week 18-27 (equivalent of a fetal stroke), causing a migration disorder and pore formation.

Congenital hemiplegia, retardation, seizures and spasticity ensue.

• Germinal matrix (area where new cells are formed, next to ventricle). Vessels are compromised due to incomplete formation of basal lamina.
• 40-50% in infants born <26 weeks, 20% in infants 25-32 weeks, <5% in normal births
• Respiratory distress, congenital heart disease, coagulopathy

Modafinil

Catoplexy is treated with SNRI's (venlafaxine), TCA's and atomoxetine

1. Cavitation and coning
2. Edema, hemorrhage and increased ICP
3. Intracranial hemorrhage, traumatic aneurysm, infection. Increased risk of seizures

Intertial damage generate shearing force on cranium on abrupt acceleration/deceleration. MRI shows small hemorrhagic contusions. 

1. Corpus callosum lesions
2. Dorsolateral brainstem lesion 
3. Axonal retraction balls

Surgical intervention can be therapeutic if minimal function is still present below the lesion

• Pneumonia
• DVT
• Decubitus (bed sore)
• UTI (from catheter)

• Massive release of dopamine, serotonin and catecholamine, with partial reuptake inhibition
• Bruxisms (teeth grinding), psychosis similar to those found in mania or schizophrenia
• Crosses BBB faster and increase half life

Adenosine receptor antagonist in basal ganglia, modulating dopamine levels.

Pregnant women and women nursing should minimize amount they use (increased half-life in babies and in pregnant women)

What is the general pathological picture for metabolic diseases? Match the deficiency with the following disorders:

• Hurler's 
• GM2 gangliosidosis (Tay-Sachs)
• Neuronal ceroid lipofuscinosis
• Pompe's disease

Neurons are "ballooned", generally seen with megaencephaly (englarged brain). Due to deficient degradation of waste product.

• Deficiency in iduronidase, causing accumulation of dermatan and hepran sulfate ("gargoyle" features, short stature, coarse face, corneal clouding, etc.)
• Deficiency in hexosaminidase, causing accumulation of ganglioside (a lipid)
• Accumulation of autofluorescent protein, with various ages of onset
• Deficiency in acid maltase, leading to accumulation of glycogen. Multi-organ dysfunction (cardiomegaly, macroglossa, hepatomegaly)

• ATP7b (metabolizes copper into ceruloplasm, allowing for biliary excretion); build up of copper in the liver spills out systemically
• Clinical presentation
  • Liver failure
  • Wing beating tremors, dysarthria, dysphonia, dysphagia
  • Gait abnormalities
  • Seizures
  • Psychological pathology (schizophrenia, manic depressive, psychosis)
  • Kayser-Fleischer rings in cornea
• Definitive diagnosis is made by liver biopsy (macronodular cirrhosis), disease targets putamen