PHRM 341 Study Guide PDF - Neurology, Psychiatry & Neurological Exam Questions

PHRM 341 – Study Guide #1 Introductions & Foundations: -​ Definitions: -​ Neurology: deals with “organic” related to brain brain structure and/or physiologic functions. -​ NERVOUS SYSTEM -​ Psychiatry: deal with “functional,” so thoughts, f...

PHRM 341 – Study Guide #1 Introductions & Foundations: -​ Definitions: -​ Neurology: deals with “organic” related to brain brain structure and/or physiologic functions. -​ NERVOUS SYSTEM -​ Psychiatry: deal with “functional,” so thoughts, feelings, moods, etc… are as much of a result of brain activity as speech, movement, and sensation. -​ MENTAL/EMOTIONAL HELP -​ Organization of Nervous System: -​ CNS (Central Nervous System) consists of the brain and spinal cord. -​ PNS (Peripheral Nervous System) consists of two types of neural cells: -​ Neurones (Neurons): basic nerve cells, which transmit messages throughout the nervous system, resulting in functions as diverse as tasing, thinking, and moving. -​ Glial Cells: provide structural and functional support to neurons. -​ Lobes of the Brain -​ Deep grooves called fissures, separate the lobes of the brain: -​ Each cerebral hemisphere has four lobes that can be identified on the surface of the brain. -​ A fifth lobe, the INSULA, lies deep within the brain. -​ Neurosynaptic transmission -​ Neurotransmission -​ Electrical neurotransmission is like electrical signaling traveling down an electrical wire. (Action potential down an axon of a neuron) -​ Chemical neurotransmission transfers from electrical to chemical to move from nerve to nerve. (Action potential reaches the axon terminal and stimulates the release of chemical neurotransmitters). -​ The Synapse -​ Neurons do not physically touch one another; two neurons are separated by a gap known as the SYNAPTIC CLEFT. -​ Binding of chemical signal to the postsynaptic neuron can: -​ Excite – increasing the generation of action potentials. -​ Inhibit – decreasing the generation of action potentials. -​ Induce other biochemical processes.  -​ Process of chemical neurotransmission -​ (1) An action potential reaches the axon terminal of the presynaptic neuron. -​ (2) Vesicles fuse with the cell membrane of the presynaptic neuron, causing an influx of calcium ions, which causes the neuron to release stored neurotransmitters into the synaptic cleft. -​ (3) The neurotransmitters cross the synaptic cleft and bind to specific receptors on the postsynaptic cleft. -​ (4) When a neurotransmitter binds to the receptor on the postsynaptic neuron it can rapidly open to close an ion channel either generating or inhibiting an action potential. -​ (5) The neurotransmitters are cleared from the synaptic cleft by reuptake into the presynaptic cleft terminals, removal by astrocytes, diffusion away, or breakdown of enzymes. -​ Neurotransmission going wrong could be in Parkinson’s Disease where signals for motor function go wrong somewhere by a communication issue between the brain and muscles. -​ Neurologic / Psychiatric Exam: -​ A mental status examination (MSE) is a structured evaluation used to assess a person's cognitive, emotional, and behavioral functioning. It is typically conducted by a healthcare professional, such as a doctor, nurse, or mental health professional. -​ The "Mini-Mental State Examination" (MMSE) is a specific, standardized cognitive screening tool used within the MSE to assess specific areas of cognitive function like orientation, memory, and language, primarily to detect potential cognitive impairment or dementia -​ Essentially, the MSE is a broader assessment that includes the MMSE as one component focused on cognitive abilities. Parkinson’s Disease and Multiple Sclerosis: PD (Parkinson’s Disease): is a common neurodegenerative disorder. -​ CARDINAL FEATURES – movement disorder consisting of: -​ Bradykinesia -​ Resting Tremor -​ Rigidity -​ Postural Instability occurs at a later stage -​ Pathological hallmark – intracellular aggregates of protein clusters (a-synuclein) in the form of Lewey bodies and Lewey neurites. -​ In normal movement control: -​ Dopaminergic pathways of the basal ganglia-thalamocortical circuit. -​ Basal ganglia regulates voluntary movement. -​ Thalamus serves as the “gateway” to the motor cortex. -​ In Parkinson’s Disease: -​ The destruction of DOPAMINERGIC neurons decline the ability to coordinate and produce movement. -​ Degeneration of the presynaptic nigrostriatal neurons result in inhibition of the thalamocortical circuit and reduced signaling to the motor cortex. -​ Loss of dopaminergic neurons = decreased dopamine. -​ Symptoms only manifest when about 80-90% DA (dopamine) lost. -​ D1r not activated = can’t initiate movement. -​ D2r not activated = tremors. -​ Overtime Lewey bodies can likely lead to cell death. -​ PD Risk Factors: -​ Increase Risk – Aging, Genetics, Male Sex, Environmental Factors (Pesticide/Herbicides, Heavy Metal Exposure, and Detergents). -​ Decrease Risk – Cigarette Smoking, Caffeine -​ Symptoms: -​ General Features (KNOW): -​ Bradykinesia (Slow Movement), Resting Tremor, Rigidity, Postural Instability -​ Motor Symptoms (SOME): -​ Hypokinectic movements (reduced arm swing), Dysarthria (slurred speech), Micrographia (small handwriting), or Dysphagia (difficulty swallowing). -​ Sensory and Mental Symptoms (SOME): -​ Bladder dysfunction, Fatigue, Pain, Decrease sense of smell, Depression, Cognitive impairment, hallucinations, or altered sleep patterns. -​ Pseudoparkinsonism: Medication Induced PD (Fake PD).  -​ Progress of Parkinson’s: -​ Premotor (pre-clinical symptoms) – REM sleep behaviors, Constipation, Depression -​ Mild (0-5 years) – PD Diagnosis, Motor Symptoms -​ Moderate (5-10 years) – Sexual Dysfunction, Sleep troubles, Anxiety -​ Severe (10-15 years) – Gait Issues, Postural Instability -​ Very Severe – Psychosis, PD dementia, Dysphagia, Dysarthria, Problems Ambulating -​ PD vs Pseudoparkinsonism diagnosis: -​ Pseudo is often bilateral, whereas PD is unilateral (one-side) -​ Pseudo experiences Action Tremors (occurs when initiates action), whereas PD experiences Postural Tremors (occurs when holding a position against gravity). -​ PD stops at the onset of voluntary action (riding a bike and then tremors stop), associated with bradykinesia. Multiple Sclerosis: is an autoimmune disease that affects the central nervous system. -​ Labs – you’d have to undergo an MRI, Spinal Tap, or have evoked potential tests to gain a diagnosis -​ General Symptoms – Fatigue, vision problems, numbness and tingling, muscle spasms, stiffness, weakness, mobility problems, pain, problems with thinking learning and planning, and depression and anxiety. -​ Higher in different areas of population. Northern States: 377 cases. Western States: 277 cases. -​ Etiology: -​ Genetic susceptibility + Environmental Factors -​ African Americans -​ Risk Factors: Geography, Vitamin D Deficiency, Excess Body Weight, Smoking, High Sodium Intake, Circadian Disruptino (Tells to you ‘wake up’ or ‘go to sleep’) or a viral infection. -​ Viral Etiology Examples: Epstein Barr Virus (EBV), Human Cytomegalovirus, human herpesvirus-6. -​ EBV -​ Molecular mimicry, Increase EB nuclear antigen complexes, 24x risk increase, or assovaited with RRMS. -​ Pathiophysiology: -​ Early stage immune cell migration to CNS (immune cells aren’t typically in CNS) -​ Demylination of axons -​ Irreparable axon damage (black holes) -​ PNS: direct cell contact, inflammatory/neurotoxic mediators -​ T-cells are resonsible for initating the cascade of auto-immunity that occurs in MS -​ Disease Progression: -​ Acute – lymphocyctic inflammation -​ Chronic – less inflammation, more remyelination -​ Relapse → inflammatory | Progressive → neurodegenerative + long-term disability -​ Diagnosing MS -​ Lesions separated in space and time. -​ Multiple lesion, multiple locations -​ Clinically definits MS (CDMS) vs Clinically Isolated Syndrome (CIS) -​ CIS – 1 lesion site -​ CDMS – multiple lesion throughout CNS -​ MRI needed to diagnos CDMS -​ Types of MS -​ RRMS (Relapsing-Remitting): “episodes of MS,” most common type, patients have distinct attacks of symptoms, these can resolve partially or completely. -​ SPMS (Secondary Progressive): developed from RRMS, disability builds up and becomes independent of any relapses. -​ PPMS (Primary Progessive): progessive from beginngin, symptoms gradually worsen, does NOT appear as sudden attacks, and usually dx older. -​ PRMS (Progressive-Relapsing): steadily worsening + occansional relapses. -​ Symptom Type: -​ Primary – nerve impulse conduction is impaired (results from remyelination and axonal damage), which results in brain damange inducing visual problems, gait problems, pain, spasticity, weakness, ataxia (impaired coordination), fatigure, tremors, etc… -​ Secondary – Recurrent UTIs, osteoporosis, depression, poor nurition, fall-related injuries, etc… -​ Teritary – Finanial hardship, personal/social problems, vocational, and emotional problems. Seizures, Epilsepy, & Status Epilepticus: Epilepsy: when at least 2 unprovoked seizures occur greater than 24 hours apart or having one unprovoked seizure and a probability of further seizures. -​ Epilepsy → Seizures | Seizures -X- Epilepsy -​ Seizures can be provoked which means something brings on it (flashing lights, illness, stress, sleep deprivation), or unprovoked meaning there is no known cause for the seizure. Seizure triggers DO NOT CAUSE epilepsy. -​ Seizure: Abnormal electrical signal (short-term def.) or hyperexcitability of neurons AND hypersynchronization of neuron firing (long-term def.). -​ Normal Neuron Firing: Excitation VS Inhibition -​ Excitation: Glutamate, Aspartate, Na+ influx, and Ca2+ currents. -​ Inhibition: GABA, Glycine, Cl- influx, and K+ efflux. -​ NOTE: Increased brain levels of GLUTAMATE would be associated with increased risk of seizures. -​ Epidemiology: Epilepsy is the 4th most common neurological disorder. -​ Risk Factors, Triggers, Medications Induction: -​ Risk Factors: premature birth with small weight, perinatal injury (anoxia), history of alcohol withdrawal, febrile seizures, or family seizures. -​ Seizure Triggers: Hyperventilation, photostimulation, physical and emotional stress, sleep deprivation, sensory stimuli, or hormonal changes during childbirth, puberty, or pregnancy. -​ Medications that induce seizures: -​ Tramadol, Bupropion, OTCs, Clozapine, Haloperidol, Theophylline, antibiotics (penicillin, cephalosporin, etc.). -​ Diagnosis: -​ EEG (Electroencephalography) – recording of brain waves/electrical activity. -​ Evaluation/Assessment: -​ (1) Patient History -​ (2) Neurologic examination -​ (3) Labs: CMP, CBC, TSH, Tox Screen -​ (4) Neuroimaging (MRI or CT) -​ (5) EEG -​ Classification Methods: -​ Where Seizure Began? Level of Awareness During One? Other Features? -​ Focal Impaired Awareness (Complex Partial): Patient has no memory of seizure (‘unawareness’). -​ Automatisms – automatic behaviors like lip smacking, chewing, picking at clothing -​ Seizure on right side: symptoms of left side of body (VICE VERSA)  -​ Symptoms by location: -​ Parietal Lobe: feeling of numbness, sensation that an arm or leg feels bigger or smaller. -​ Temporal Lobe: a ‘rising’ feeling in the stomach (deja vu), getting unusual smell, sudden intense feeling of fear or joy, or oral and manual automatisms -​ Occipital Lobe: visual disturbances, or visual hallucinations. -​ Generalized Non-motor (Petit Mal): whole-brain involvement seizure that would give you a shortness of consciousness (blank stare/motionless), rapid eye blinking, and lasts only 10-30 seconds long. -​ Generalize Motor / Tonic Clonic (Grand-Mal): loss of consciousness, TONIC (increased muscle tone or whole body stiffness), CLONIC (rhythmic jerking), Post-ictal period, tongue biting, and lasts 1-3 minutes. -​ Unprovoked Seizure: permanent changes in cortical function. -​ Epileptogenic region or focus – an aggregate of neurons within the brain that are hyperexcitable and remain in a state of partial depolarization. Status Epilepticus (SE): 5 or more of continuous clinical and/or electrographic seizure activity or recurrent seizure activity without recovery between seizures. -​ GCSE (Generalized Convulsive Status Epilepticus): Convulsions that are associated with rhythmic jerking of extremities. -​ NCSE (Non-convulsive status Epilepticus): Seizure activity on an EEG without any associated clinical findings. -​ Etiology: -​ Type 1 (no structural lesion) – no apparent structural damage -​ Infection, Metabolic, Low AED levels, Alcohol, Idiopathic -​ Type 2 (structural lesion) – structural damage -​ Anoxia/Hypoxia, CNS tumor, CVA, Drug overdose, Hemorrhage, Trauma -​ Morality survival decreases with increasing age. -​ Pathophysiology: -​ “Seizures Beget Seizures” (more seizures activity the brain experiences, the brain will continue that pattern. -​ May result in ischemia (brain damage) if seizures continue -​ Neurologic & Physical Damage -​ Phase I (< 30 minutes) -​ Phase II (> 30 minutes) -​ Diagnosis -​ Observation, Nature and Duration of Seizure(s), EEG, Neurologic imaging, Physical examination, and Lab assessment -​ Clinical Presentation: -​ Symptoms: Impaired consciousness, post-seizure disorientation, and pain associated with injuries -​ Early Signs: Generalized convulsions, hypothermia or fever, incontinence, and normal BP -​ Late Signs: Pulmonary edema with respiratory failure, cardiac failure, hypotension or HTN, and Rhabdomyolysis Dementia & Alzheimer’s Disease: Dementia: -​ Reversible: -​ (D)rug (anticholinergic activity) -​ (E)motional (depression) -​ (M)etabolic (hypothyroidism = TSH is increased) -​ (E)yes and Ears declining -​ (N)ormal pressure hydrocephalus (fluid around brain) -​ (T)umor or another lesion -​ (I)nfection (syphilis, AIDS) -​ (A)nemia (Vitamin B12 or Folate deficiency) -​ Caused by modifiable factors such as: -​ Medications that may cause cognitive impairment – Anticholinergics (drugs that block the action of a neurotransmitter called acetylcholine) – Diphenhydramine, nortriptyline, amitriptyline, or oxybutynin. Opioids, antihypertensive/cardiac meds, hypoglycemia meds, or sedatives. -​ Medications that may cause vitamin deficiencies: phenytoin, carbamazepine and phenobarbital cause vitamin b12 and folic acid deficiencies. Methotrexate causes a folic acid deficiency. Metformin causes a vitamin b12 deficiency. -​ Irreversible: condition associated with cognitive or behavioral symptoms that cannot be fully reversed. (2 forms) -​ PROGRESSIVE – Alzhemier’s Disease, Vascular Dementia, Lewy Body Dementia, PD Dementia, Frontotemporal Dementia, or Mixed Dementia -​ Alzheimer’s Disease (AD) is the most common cause of dementia. -​ Degeneration of CHOLINERGIC NEURONS (use the neurotransmitter acetylcholine to send messages). -​ Diagnosis: -​ Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains. -​ IADLs (Instrumental Activities of Daily Living) – Using a phone, traveling, preparing meals, housework, financial management. -​ ADLs (Activities of Daily Living) – Bathing, Dressing, Toileting, Feeding -​ Risk Factors: -​ Non-Modifiable – Age, Sex, ApoE4 allele (inherited is very small %), Family History, or Head Trauma. -​ Modifiable – Hypertension, Diabetes, Dyslipidiemia, Depression, Mild Cognitive Impairment, Obesity, Smoking, Physical Activity, or Diet. -​ Assessment: -​ MMSE (Mini-Mental State Examination): 30-point based assessment tool for AD -​ Normal Cognitive function = 25-30 -​ MILD Impairment = 20-24 -​ MODERATE Impairment = 10-19 -​ SEVERE Impairment = Left side -​ Triggers – Light touch, chewing/eating, speaking -​ Women > Men Postherpetic Neuralgia (PHN): patients infected with chickenpox as a child (Virus remain dormant until reactivated). -​ Herpes Zoster (Shingles) presents as vesicular rash -​ Thoracic > Cervical > Trigeminal -​ Cause Acute infection -​ Patients can experience pain once healed. (20% following infections, typically after 3 months) -​ Female Sex is most likely to get. -​ Severe acute pain -​ Immunity declines as age increases and immunosuppression. Diabetic Peripheral neuropathy (DPN): damage of peripheral nerves in the feet and hands -​ Metabolic AGEs & Vascular changes due to diabetes -​ AGEs – advanced glycation end-products. -​ Symptoms: -​ Painful/Unpleasant – Lancinating pain, electric-like pain, burning sensation, paresthesia (tingling/pins and needles), allodynia and hyperalgesia. -​ Nonpainful (negative) – Numbness, loss/decrease of sensation and deep tendon reflexes -​ Risk Factors: -​ Definite Risks – Poor glycemic control, and duration of diabetes. -​ Potential Risks – HTN, hyperlipidemia, smoking, obesity, and excessive alcohol use. Fibromyalgia (FM): COMPLEX chronic pain syndrome characterized by chronic widespread pain & other symptoms. -​ Symptoms – morning stiffness, fatigue, depression, anxiety, sleep disturbance, headaches, IBS, bladder problems, etc… -​ Women >> Men -​ Etiology: -​ Central sensitivity syndrome – central augmentation of pain and sensory processes. -​ Increased level of excitatory neurotransmitters. -​ DECREASE NE and 5-HT IN THE BRAIN. Substance Use Disorder: Substance Use Disorder (SUD): continued use of a substance despite significant consequences. -​ Definitions: -​ INTOXICATION: symptoms & behaviors caused by a substance’s effect on the CNS. -​ TOLERANCE: decrease in body’s response to a drug dose with continued use. Higher doses needed to elicit effects lower doses used to bring. -​ WITHDRAWAL: physically and mentally unpleasant signs & symptoms that surface in absence, or significant, reduction in drug use. -​ DEPENDENCE: substance’s pharmacological effect changes the body’s homeostatic functioning. -​ ADDICTION: a chronic relapsing disorder characterized by compulsive drug seeking and use despite adverse consequences. -​ SUD are synonyms with addiction -​ SUD more socially acceptable, Addiction invites stigma. -​ Activities that used to be enjoyable are not as fun…. :( -​ Risk Factors: -​ Epigenetics (environmental effect on person's gene expression) -​ Adolescents -​ Mental Disorders. -​ Pathophysiology: -​ Dopaminergic neurons originate in VENTRAL TEGMENTAL AREA (VTA) and project into forebrain, including NUCLEUS ACCUMBENS -​ All drugs or actions that release DOPAMINE (DA) in the nucleus accumbens are associated with misuse. -​ Amygdala, hippocampus, and medial prefrontal cortex respond to natural reinforcers. -​ Repeated use leads to rewiring of brain networks. -​ Diagnosis: -​ DSM-5 organised into 4 categories: -​ Impaired Control, Risky Use, Social Impairment, or Psychological indicators -​ At least 2 occuring in a 12 month period. Alcohol Use Disorder (AUD): one of the leading causes of preventable deaths in the U.S. -​ Exerts on endogenous opioids & neurotransmitters (GABA, Glutamate, Serotonin, and Dopamine). -​ GABA = major inhibitory neurotransmitters that has binding sites for ethanol -​ Releases GABA → inhibitory effect -​ Block NMDA glutamate receptors → inhibitory effect  -​ Alcohol-Acute Intoxication: -​ Euphoria, Disinhibition, Altered perception/judgement, slurred speech, ataxia (poor muscle control), nystagmus (eye make uncontrolled movements, hyperreflexia (exaggerated reflexes), slowed reactions, and impaired memory. -​ Feel-good effects step from acute release of dopamine in VTA & beta-endorphins. -​ 3 Major Enzyme Systems with Hepatocyte (know the one listed): -​ ALCOHOL DEHYDROGENASE (ADH): alcohol → (via ADH) → acetaldehyde. -​ Zero-Order Kinetics – Blood alcohol decreases at a constant amount per unit of time. -​ Rate - Limiting Factor = TIME -​ First-Order Kinetics – at very high and very low concentrations. -​ Alcohol Withdrawal: -​ Requires hospitalization and pharmacological treatment. -​ Presentation: tachycardia, diaphoresis, hypertension, hyperthermia, nausea, vomiting, tremors, and hallucinations. -​ DELIRIUM TREMENS (DT) and seizures are most severe -​ Mechanism of seizure: depressant discontinuation → excitatory overload → seizure. -​ Labs & Monitoring: -​ CIWA-Ar Scale: score patient’s baseline symptoms and ongoing monitoring. -​ Labs: BAC, CBC (anemia), CMP (electrolytes), Tox screen -​ AUD Risk Factors: -​ Phenotype – Aggression, Depression, Impulsivity, Novelty-Seeking, Early Exposure -​ Environment – Religious background, place of residence, history of sexual abuse, being single, deceased parents -​ Diagnosis: -​ Alcohol Use Disorders Identification Test (AUDIT) -​ CAGE questionnaire -​ Complications of AUD: -​ Wernick’s encephalopathy (thiamine deficiency due to malabsorption) Opioid: naturally, synthetic, or semi-synthetic chemicals that interact with opioid receptors found in the brain and other organs. -​ Definitions: -​ Opiates: specifically natural compounds derived straight from poppy plants (opium/morphine). -​ Opioids = natural or synthesized in a lab. -​ Synthetic opioids = methadone, tramadol, fentanyl) are more potent than opioids -​ Opioid Pathophysiology: -​ Bind to MU RECEPTORS to mimic endogenous endorphins. -​ Exposure to opioid → release of DA to D1 receptors → cyclic AMP (cAMP) activation → downstream effects → experiencing feelings of euphoria → association of drug, their surrounding environment, and situation -​ DA release also conditions NMDA receptors to increase glutamate signaling → disordered response to opioids → habit formation. -​ SEROTONIN, GABA, acetylcholine, endogenous opioid and cannabinoid compounds involved in indirect signaling in nucleus accumbens. -​ Acute Intoxication: -​ Signs – miotic pupils, scratching, decreased respiratory drive, loss of consciousness, death -​ Symptoms – euphoria, dysphoria, apathy, lethargy, impaired motor skills -​ Opioid Withdrawal: -​ Onset of 8-24 hours for short-acting opioids and 36-72 hours for a long-acting (methadone) -​ Opioid withdrawal, itself, is not dangerous -​ COWS (Clinical Opiate Withdrawal Scale) = commonly used clinician-rated tool for monitoring symptoms and treatment effectiveness. -​ Signs – sweating/tachycardia, HTN, hyperthermia, lacrimation, restlessness, tremors, etc.. -​ Symptoms – body aches, abdominal cramping, diarrhea, nausea/vomiting, anxiety, agitation, and insomnia. -​ Opioid Use Disorder (OUD): chronic, problematic pattern of opioid use leading to problems or distress, with at least 2 symptoms present in a 12 month period. Headaches & Headache Disorders: Primary Headache: No known underlying cause. Secondary Headache: Result of another condition such as an infection, vascular disease, trauma, or psychiatric disease. -​ Headache History & Exam: -​ Frequency, Duration, Character, Severity, Location, Quality, Triggering/Aggravating/Alleviating Features -​ Age of Onset, Family History, Lifestyle, and Comorbid conditions. -​ Medication Reconciliation, Neurologic Exam, Physical Exam, Labs, and Imaging -​ Primary Headache – MIGRAINES, Tension-type headaches, or Cluster headaches. -​ Migraine: -​ More common in 25-55 year-olds and in women. -​ Half of migraine patients have onset before 20 years old. -​ Risk Factors – genetics, metabolism, female, head injury, depression, anxiety, or comorbid pain disorders. -​ Triggers – stress, hormones, drugs, not eating, environment, lack of sleep, odor, lights, alcohol, or smoking. -​ Pain experience comes from the release of CGRP and imbalance of serotonin stimulation. -​ Mechanisms: -​ Hypothalamic activation, altered brain connectivity, brainstem activation, cortical spreading depolarization, and release of CGRP (calcitonin gene-related peptide) and PACAP (pituitary adenylate cyclase-activating polypeptide). -​ Activates Trigeminovascular system -​ 4 Phases of Migraines: -​ PRODROME – Present in 60% of patients, can precede headache by hours to days, may experience depression, hyperacitivty, cognitive changes, frequent urination, etc… -​ AURA – symptoms grow over 5 minutes and last up to an hour, fully reversible set of nervous system symptoms, positive and negative symptoms (visual and sensory), and recedes 60 minutes before headache begins. -​ HEADACHE – unilateral, moderate to severe intensity. -​ POSTDROME – impaired concentration of fatigue. -​ Tension-Type Headache: -​ Affects 78% of the population, more common in women. -​ Risk Factors – Stress, Poor health, and lack of sleep. -​ Increased nociceptive processing in the Central Nervous System  -​ Chronic nociceptive input for pericranial myofascial tissues -​ Central sensitization over time -​ Headache lasts 30 minutes to 7 days. -​ 2-4 Characteristics: -​ Bilateral location, pressing to tightening quality, mild to moderate intensity, or not aggravated by physical activity. -​ Both of the following – no nausea or vomiting and only either photophobia or phonophobia (not both). -​ Headache Categories: -​ Infrequent Episodic – at least 10 episodes occurring less than 1 day a month ( 180 days per year). -​ Lasts hours to days or unremitting -​ Only 1 – photophobia, phonophobia, mild nausea -​ Cluster Headache: -​ Population prevalence 0.1%, Male to female ratio 2:5:1 to 3:5:1, Ages 20-40 year olds -​ Patients with 1st degree relatives have a 10-50x higher chance of developing cluster headaches. -​ Correlation with smoking. -​ MOA not completely understood but: -​ Elevated plasma calcitonin gene-related peptide level (CGRP) -​ Vasodilation and perivascular edema from trigeminal parasympathetic overactivity. -​ Headache Category: -​ Episodic – Occurring in cluster periods, at least two cluster periods lasting 7 days to 1 year (untreated), separated by pain free remission periods of at least 3 months. -​ Chronic – occurring without a remission period or with a remission period less than 3 months. -​ For at least 1 year. -​ Medication Overuse Headache: -​ Headache greater than or equal to 15 days per month. -​ Patient has a pre-existing headache disorder. -​ Regular overuse for greater than 3 months of meds for acute or symptomatic treatment. -​ Regular Intake of drug greater than or equal than or equal to 10 days to at least 3 months -​ Ergotamine, Triptans, Opioids, or Combination Analgesics -​ Regular Intake of drug greater than or equal than or equal to 15 days to at least 3 months -​ Acetaminophen, NSAIDS, or Aspirin. Major Depressive Disorder & Bipolar Disorder (MDD & BPD): MDD – Extremely Complex -​ Cannot be narrowed down to a single theory -​ Several Factors – Sex, Gender Identity, Race, Ethnicity, Culture, Social Status, Genetics, Environment -​ Actual Prevalence has increased lifetime prevalence – 7-15% -​ 1.5-2.5 times higher in females than males -​ Adolescents – 19.4% females, and 6.4% males (ages-12-17) -​ Tends to occur within families -​ MDD Pathophysiology: -​ NEUROTRANSMITTERS INVOLVED – SEROTONIN & NOREPINEPHRINE (most important) -​ Monoamine hypothesis – Serotonin (5-HT), Dopamine (DA), and Norepinephrine (NE) → decreased levels -​ GABA receptors, neuroactive steroids, endogenous opioids, nutritional imbalances. -​ Chronic Stress Model – Hypothalamic-Pituitary-Adrenal (axis) -​ Stress Effect – increased cortisol, glucocorticoids; decreased allopregnanolone. -​ NEUROTRANSMITTERS DO NOT FUNCTION INDEPENDENTLY -​ 5-HT and NE are thought to be the major contributors to MDD -​ Hippocampal volume of the brain is smaller in MDD than healthy controls -​ Neuroactive Steroids: -​ Progesterone metabolite and Allopregnanolone (release increase in settings of acute stress). -​ Brain-Derived Neurotrophic Factors (BDNF) – primary mediator of inflammation and overexcitation. Promotes survival of neurons and neuroplasticity. -​ Chronic Stress associated with glucocorticoids such as cortisol may lead to decrease BDNF -​ BDNF has been shown to decrease expression of GABA. -​ Glutamate and GABA transmission – increased GABA receptor activation results associated with decreased transmission of 5-HT and NE. -​ Clinical Presentation: -​ Emotional – diminished ability to experience pleasure, loss of interest and pleasure in usual activities, pessimism (hopelessness), and voices saying negative comments or suggesting suicide. -​ Physical – chronic fatigue resulting in decreased daily activity, fatigue does not improve with rest, changes in sleep, appetite changes, and GI disturbances.  -​ Cognitive – decreased concentration or slowed thinking, poor memory of recent events, or confused or indecisive. -​ Psychomotor Disturbances – slow physical movements/speech/thought processes and restlessness/outbursts of anxiety or agitation. -​ Diagnosis of MDD -​ At least 5 or more present for a single MDD episode. -​ At least one symptom must be a depressed mood or loss of interest or pleasure in nearly all activities. -​ Must be present nearly every day for at least 2 weeks minimum. -​ MDD Evaluation -​ Medical/Family/Social History -​ Labs: CBC, CMP, TSH, Folate levels, & Urine Drug Screen -​ PHQ-9 Examination: -​ Score of 0-27 -​ 0-4 Minimal, 5-9 Mild, 10-14 Moderate, 15-19 Moderately Severe, or 20-27 Severe. -​ Secondary Causes of Depression -​ Medical Causes – Folate Deficiency and Hypothyroidism -​ Depression Mimics (need to rule out) – Anemia, Hypotension, and Chronic Fatigue Syndrome BPD (Bipolar Disorder) – thought to be influenced by developmental, genetic, neurological and physiological factors. -​ Bipolar I (1%), Bipolar II (1.1%), and Subthreshold bipolar (2.4%). -​ Symptoms Onset – Occurs in late adolescence or early adulthood, or one-third to two-thirds experience the first episode as a child or adolescent. -​ Pathophysiology Theory: -​ Gene loci related to calcium channel, cardiac dihydropyridine-sensitive (CACNA1C), and ankyrin 3 (ANK3) involved in hereditary mood disorders. -​ Amygdala within the limbic system and prefrontal cortex may contribute to functional abnormalities. Altered synaptic and circuit functioning rather than dysfunctioning of individual neurotransmitters. -​ Environmental, physiological, immunological and sleep dysregulation. -​ MANIA: AT LEAST 1-WEEK PERIOD of abnormally and persistently elevated mood and energy, associated with at least three of the following symptoms: -​ (D) – Distractibility (poor attention) -​ (I) – Indecrection (pleasurable activities with high risk consequences) -​ (G) – Grandiosity (inflated self-esteem) -​ (F) – Flight of Ideas (racing thoughts) -​ (A) – Activity increase (increase goal-directed activities) -​ (S) – Sleep deficit (decreased need for sleep) -​ (T) – Talkativeness (pressure of speech) -​ MUST BE SEVERE ENOUGH TO CAUSE FUNCTIONAL IMPAIRMENT -​ HYPOMANIA: AT LEAST 3 DAYS of abnormally and persistently elevated mood and energy, associated with at least three of the following symptoms: -​ (D) – Distractibility (poor attention) -​ (I) – Indecrection (pleasurable activities with high risk consequences) -​ (G) – Grandiosity (inflated self-esteem) -​ (F) – Flight of Ideas (racing thoughts) -​ (A) – Activity increase (increase goal-directed activities) -​ (S) – Sleep deficit (decreased need for sleep) -​ (T) – Talkativeness (pressure of speech) -​ SYMPTOMS NOT SEVERE ENOUGH TO AFFECT FUNCTION -​ Classification: -​ BP I Disorder – Manic Episode +/- major depressive or hypomanic episode -​ BP II Disorder – Major Depressive Episode + hypomanic episode -​ Rapid Cycling Bipolar Disorder I or II – When 4+ mood episodes in a 12-month period. Female > Male. -​ Persistent Depressive Disorder (Dysthymia) -​ Depressed mood most days for at least 2 years (1 year in children and adolescents)  -​ Cyclothymic Disorder -​ Chronic fluctuations between subsyndromal depressive and hypomanic episodes -​ Unspecified bipolar and related disorders -​ Mood states do not meet full criteria for any specific disorder in the bipolar and related disorders -​ Secondary Causes of Mania: -​ Medical condition – CNS Disorders, Infections, Electrolyte Abnormalities, or Endocrine or hormonal dysregulation. -​ Medications or Drugs that induce mania: -​ Alcohol Intoxication, drug withdrawal states (antidepressants), DA - augmenting agents (CNS stimulants like amphetamines/cocaine), Hallucinogens, or Cannabis intoxication. -​ Somatic therapies that induce mania -​ Bright light therapy, deep brain stimulation, and sleep deprivation. Insomnia: Insomnia Disorder: Sleep disorder characterized by long sleep latency, issues with sleep maintenance (such as frequent nocturnal awakenings and/or prolonged periods of wakefulness during the sleep period), or a combination of these). -​ Leads to someone getting too little sleep/poor quality of sleep so they may not feel refreshed/energized when waking up. -​ 2 kinds: -​ Acute – Sleeping difficulties last a few days to a few weeks but no longer than 3 months -​ Chronic – Sleeping difficulties and daytime symptoms occur at least 3 days/weeks for > 3 months. -​ Insomnia can also be a symptom -​ Illness – Pain, Breathing Issues, Thyroid Issues -​ Poor Sleep Hygiene – Blue lights, Caffeine, Alcohol, or Daytime inactivity -​ Acute Stress – Emotional, Late Exercise, and Environmental -​ Epidemiology – about 10% of the world’s population experience insomnia disorder -​ Onset – tends to occur in adulthood vs childhood/adolescence. -​ Prevalence: -​ Tends to be higher in the elderly and tends to affect women more often than men -​ Risk Factors – Female, Olde age, inactive lifestyle, lower socioeconomic status, medical conditions, psychiatric disorders, irregular sleep schedule, having immediate family members with insomnia, light sleeper, RLS (restless leg syndrome), or alcohol use. -​ Complications of Insomnia: -​ Slowed reaction time and inattention/memory issues -​ Mental health conditions (depression, anxiety) -​ Daytime sleepiness and lack of energy -​ Lower performances at work, school, etc. -​ Higher risk of health conditions such as HTN, heart attack, stroke, diabetes, etc… -​ Benefits of adequate sleep: -​ Lower rates of chronic health conditions, Learning and memory consolidation, Cognitive/Social/Physical Performance, Emotional Wellbeing -​ Neurochemistry of sleep -​ Wake Promoting Neurotransmitters – NE, Acetylcholine, Histamine, 5-HT, DA, and Orexin (hypocretin) -​ Sleep Promoting Neurotransmitters – GABA, Adenosine, and Melatonin -​ Proper Sleep Hygiene Habits -​ Maintain stable bedtimes/rising times, Spend no more than 8 hours in bed, Spend no more than 20 minutes awake in bed, experience regular daytime light, maintain a quiet, dark bedroom, maintain adequate nutrition, etc… -​ Pathophysiology: -​ Insomnia happens due to neurochemical/structural issues in the system responsible for controlling the sleep/wake cycle and/or the circadian biological clock system. -​ CIRCADIAN BIOLOGICAL CLOCK regulates timing to sleep and wakefulness -​ DSM-5 Classifications: INSOMNIA DISORDER, hypersomnolence disorder, narcolepsy, breathing/circadian sleep disorders, non REM sleep arousal disorders, nightmare disorders, RLS, or substance or medication induced sleep disorders. -​ DSM-5 Criteria: -​ Unsatisfactory sleep quantity or quality + presence of > 1 of the following: -​ Difficulty with sleep latency -​ Difficulty with sleep maintenance -​ Early morning awakening -​ Other Significant Criteria: -​ Significant distress or impairment in social, occupational, or other areas of functioning (such as sleepiness, difficulty concentrating, etc..) -​ Sleep difficulty happens with adequate sleep opportunities. -​ Sleep complaints for > 4 nights per week and have been present for at least 3 months. -​ Not associated with other sleep disorders, substance use, psychiatric disorders, or other medical disorders. -​ Clinical Presentation: -​ Pharmacologically induced insomnia – anticonvulsants (felbamate, topiramate), central adrenergic blockers (Doxazosin), diuretics (Chlorthalidone), SSRIs (fluoxetine), Steroids (Dexamethasone), Stimulants (Amphetamines).  -​ Polysomnography -​ Electroencephalogram (EEG), Electrooculography (EOG), and Electromyography (EMG) Sleep Apnea (NOT INSOMNIA): repetitive episodes of cessation of breathing during sleep -​ Followed by blood oxygen and desaturation AND -​ Brief arousal from sleep to restart breathing -​ Result – fragmented sleep, poor sleep architecture, and periods of apnea and hypopnea