Clin Med III Exam 1: Endocrine, Neuro

Cushing Disease Cause: Overproduction of glucocorticoids (cortisol), usually d/t benign ACTH-secreting pituitary adenoma. Either 1) ATCH dependent (high ACTH) or 2) ACTH independent (normal-low ACTH). Also d/t exogenously administered gluccocorticoids (ex. autoimmune, asthma) resulting in hypercortisolism. Women > Men. S/sx: Clinical manifestations may be subtle. Most ppl who look like they have Cushing's don't. Most have a pituitary tumor that is producing ACTH Obesity, moon face, muscle wasting, HTN, HA, psych changes. Skin: thin, fragile, easy bruising, poor wound healing, hirsutism, striae (abdomen), acanthosis nigracans/hyperpigmentation (d/t ↑ ACTH) Dx: 1) Start w/DST - dexmethasone suppression test: measures whether ACTH secretion by the pituitary can be suppressed. Low dose (1 mg): no ACTH suppression = Cushing dz

2) 24-hour urine free cortisol: >3x NL = significant 3) Late-night salivary free cortisol: measure 11p-12 (x2) High dose dexamethasone (8 mg) distinguishes Cushing from paraneoplastic syndrome: if a tumor is causing hypercortisolism, the ACTH will not ↓when dexamethasone is on board. Lab results: ↑glucose/triglycerides/WBCs, urinalysis = glucosuria. Serum ACTH: if taking chronic high dose steroids will be low, if d/t pituitary Cushing dz = high. D/t adrenal tumor secreting cortisol = low Imaging: MRI pituitary, CT adrenals. Tx: Meds that inhibit steroid genesis. Adrenal adenoma = adrenalectomy. Pituitary adenoma = surgical removal of tumor

Dementia/Alzheimer's Dz Memory impairment plus: aphasia OR apraxia (inability to perform particular purposive actions) OR agnosia (inability to interpret sensations and hence to recognize things). Causes: Degenerative = alzheimer's dz, huntingtons, parkinsons Vascular = multiple infarcts, hypoperfusion (MI, hypotension), subdural hematoma, SAH. Infectious = meningitis, neurosyphilis, viral encephalitis (HIV, herpes) Inflammatory = lupus, demyelinating dz Also neoplastic, traumatic, hydrocephalic, toxins, metabolic, psych DISTURBANCES IN EXECUTIVE FUNCTIONING - must cause impairment in social/occupational function. Decline from previously higher level of functioning. ↑ w/age, ♀>♂ Alzheimer's MC, also vascular dementia, Lewey body dementia (dysfunction of cerebral hemispheres). Check for syphilis, B12, chem panel, drugs, HIV, lyme dz. Risk factors: Alzheimer's = age, Down's syndrome, ♀, ↓ educational level, family hx of early onset AD, genetics, +/- head trauma, HTN, CVA, thyroid dz, organic solvent exposure Early s/sx alzheimer's dz: Difficulty w/finances, meds, meals. Repetitive questions (ominous). Stop reading, stop hobbies. Social interaction preserved early. Mid stage: ↓ recent memory, trouble w/comprehension, naming, grammar. Disorientation in familiar settings, personality changes, impaired insight/judgement Late stage: Info/memories gone Sparse speech, ADL dependence, +/- seizures. Eventually mute, bedbound. Course = 7-10 years.

All d/t cortical atrophy in temporoparietal, limbic, posterior cingulate prominently. Synaptic losses, deposition of plaques. Cholinergic neurotransmission deficits also contribute to the progression of Alzheimer's due to the stress on the neurons due to neurofibrillary tangles that can start over *20 years prior* to symptoms Prevention alzheimer's = none Tx Alzheimer's: Cholinomimetics: ↓ levels of cholinergic markers on neurocortex - can slow progression in early-mid dz - not effective past 3 yrs Memantine: uncompetitive N-methyl-D-aspartate receptor antagonist - acts on glutamate transmission - slows progression of functional decline Vascular dementia: 2nd MC cause of dementia Usu. from multiple small infarcts of subcortical structures (basal ganglia, thalamus) - occlusion of small penetrating arteries → vascular risk factors/age Initial recovery likely. Dx: Stroke-like events, focal neuro deficits w/MRI findings Prevention: ↓ risk factors, ASA, plavix, anticoags Lewey body dementia: Main component of Lewy Bodies = Alpha-synuclein protein - function unknown still Found in other dementia's including Parkinson's dementia with movement symptoms - rigid muscles, shuffling walk, trouble instigating movement

Essential/familial tremor Present w/action (intention) NOT present @ rest Symmetric tremor of hands/head/voice BILATERAL onset any age, >60 MC Worse w/stress, intentional movement Relieved with alcohol Cause unknown, assoc. w/aging, genetics, +/- environmental

Cerebellar tremor = intention tremor. Unilateral or bilateral. Usually extremities, worse @ end-point. Dysmetria (misjudge distance to target = past-pointing), ataxia Tx: If mild observe, if not, meds. 1st line = propranolol, primidone (acts on GABA receptors to inhibit synaptic transmission). 2nd line = gabapentin, benzos (try to avoid), topiramate. DBS

Hyperparathyroidism Causes 1. Head and neck surgery account for the majority of cases—thyroidectomy, para- thyroidectomy, radical surgery for head and neck malignancies. 2. Nonsurgical hypoparathyroidism is rare. Clinical features 1. Cardiac arrhythmias 2. Rickets and osteomalacia 3. Increased neuromuscular irritability due to hypocalcemia a. Numbness/tingling—circumoral, fingers, toes b. Tetany • Hyperactive deep tendon reflexes • Chvostek's sign—Tapping the facial nerve elicits contraction of facial muscles. • Trousseau's sign—Inflating the BP cuff to a pressure higher than the patient's systolic BP for 3 minutes elicits carpal spasms. c. Grand mal seizures 4. Basal ganglia calcifications 5. Prolonged QT interval on ECG—Hypocalcemia should always be in the differen- tial diagnosis of a prolonged QT interval. 6. Cataracts

Diagnosis 1. Low serum calcium 2. High serum phosphate 3. Serum PTH inappropriately low 4. Low urine cAMP Treatment 1. IV calcium gluconate in severe cases, oral calcium in mild to moderate cases 2. Vitamin D supplementation (calcitriol) 3. Note that both vitamin D and calcium replacement can increase urinary calcium excretion, precipitating kidney stones. Therefore, administer with caution to avoid hypercalciuria (the goal is to keep serum calcium at 8.0 to 8.5 mg/dL).

Hyperthyroidism (Thyrotoxicosis) Hypermetabolic state d/t ↑↑ T3 and T4 D/t stimulation of TSH receptor (Graves dz) Pituitary adenoma causing ↑ TSH HCG in pregnancy Autonomous thyroid nodules that secrete excess hormones (multinodal goiter, thryoid adenoma, thryoid cancer). Also caused by drugs (levothyroxine OD), amiodarone, iodine, thyroid inflammation, struma ovarii S/sx: ↑ metabolism, diaphoresis, heat intolerance, tachycardia, ↓periph. resistance, HTN, bounding pulses, widened pulse pressure, ↑ CO, a-fib, ↓ attention span, ↑ wasting/weight loss, oligomenorrhea, osteoporosis, nervousness/anxiety, freq. defecation, hyperreflexia. Grave's disease: MC cause of hypothyroidism. Production of antibodies that stimulates TSH receptors and overproduce T3 and T4. MC in women 20-40. Genetic. Association w/other autoimmune diseases. S/sx: *Goiter, xopthalmus, pretibial myxedema*, finger clubbing.

Dx: Based on clinical finding and labs (Labs = low/undetectable TSH, high free T4/T3, + thyroid stimulating Ab's). If T4 normal, determine T3 Tx: Inhibit T3/T4 synthesis with methimazole, propylthiouracil - inhibit iodine → inhibit conversion of T4 → T3. Also inorganic iodide, B-adrenergic antagonists for s/sx (propranolol), radioactive iodine, thyroidectomy Thyroid storm: ↑ s/sx of hyperthyroidism, may be caused by infection, trauma, surgery, DKA, radiation. S/sx = fever, diaphoresis, tachycardia, Afib, CHF, tremors, NV, abd pain, AMS, hypotension, pulm edema. Tx = ICU, cooling, PTU/methimazole, steroids Dx: Serum TSH first. If normal and no s/sx of thyroid dz, all done. If low, check T4. If high, or if normal and s/sx of thyroid dz, check T4. Treat low T4, if normal tx based on TSH levels or sx. Both serum TSH and free T4 should be drawn if suspect pituitary or hypothalamic dz suspected

Migraine HA Tend to be familial, MC ♀ 30-39. MC no aura. Cortical spreading depression, self-propagating wave of neuronal and glial depolarization that spreads across cerebral cortex. Causes aura, activates trigeminal nerve → inflammatory changes in meninges = allodynia (head pain). Concerns: First/worst HA of life that intensifies quickly, change in HA pattern, fever, focal neuro deficits, MS change, abrupt HA w/exercise, visual field deficits, HA with HTN (pheo), HA <5 or > 50 yo (suspect pathology), new HA in HIV, cancer, preggos Prodrome ~60%: euphoria, irritability, food cravings 24-28 hrs prior Aura - focal visual, sensory or motor neuro disturbance w/and w/out HA developing in >5 mins. Photophobia/phonophobia common, also cutaneous allodynia. Triggers = stress, menstruation, visual stimuli, weather changes, nitrates, fasting, wine. Complex migraine: mimics stroke/TIA, presents w/wo HA. New onset

Dx: New onset HA w/normal neuro exam = labs, CT optional New onset HA w/abnormal neuro exam = labs w/Mg+, CT, MRI. Add LP if febrile w/meningeal signs CT in new onset HA > 40 yo Ask about OCP Tx: Mild = Tylenol (preggos), NSAIDs, ASA, naprosyn, Tordol, Moderate = tylenol with ISOMETHEPTENE MUCATE, reglan (nausea), topamax, valproate Severe = Dihydroergotamine (1 mg subcutaneously or 0.5 to 1 mg intravenously) along with an anti-emetic Ketorolac 60 mg IM benadryl, caffeine, NO narcotics d/t rebound HA and abuse potential. Prevention: for pts with debilitating HAs > 3 days/month = B-blockers, CCBs, NSAIDs, TCAs, anticonvulsants Peds: ♂>♀ after age 12 Primary HA MC cause, illness 2nd Occipital HA rare - suspect structural lesion Shorter duration Abdominal migraine = abd pain w/neuro s/sx

Multiple Sclerosis Inflammatory demyelinating disease that destroys myelin in the CNS and manifests as neuro dysfunction. The only COMMON demyelinating disease. Risk factors: +/- viruses (HSV, EBV), ♀, ↓ vit D (esp in northern hemisphere), genetics, smoking, sun exposure Patho: Oligodendrocyte produces myelin in CNS. T cell in the blood crosses the BBB and attaches to the myelin because it sees it as foreign. Releases cytokines (interleukins, TNF-alpha, interferon-gamma). Recruits more T cells, damages BBB, opens it up, then B cells/macrophages get in and destroy myelin S/sx: Motor weakness, visual disturbances, sensory loss - all *exacerbated by heat and stress*. Sensory disturbances unrelated to anything else - think MS. Types: Relapsing-remitting (RRMS): MC, best prognisis (although 85% progress to next). Short duration, may remain w/o s/sx for months/years Secondary-progressive (SPMS): slow, steady progression, w/or w/out relapses that do not fully remit Primary-progressive (PPMS): steady worsening from the start, no relapses/remissions Progressive-relapsing (PRMS): steadily worsening from the start, flare-ups, w/or w/out remission Prognosis: Rule of Thirds: 1/3 still ambulatory w/o issue. 1/3 need assistance to walk. 1/3 need a wheelchair/nursing care Favorable predictors: younger age @ onset, sensory sx, ♀, RRMS pattern.

Dx: Separated in time and space: 2 separate CNS sx in 2 separate places in brain, 2 attacks separated in time. Age 10-50 (20-40 MC) Objective deficits on exam, no other explanation for presentation. CSF fluid = oligoclonal bands, most IgG. Evoked potentials - visual (flickering pattern → depolarization - if speed of impulse is too slow = nerve damage), brainstem, auditory. Dx: MRI w/contrast (gadolineum). Shows active lesions: new/bigger, multifocal lesions - "plaques" of spine/brain. Plaques = discrete region of demyelination w/preservation of axons → acute inflammation. Black holes = plaques in chronic stage - signifies axonal destruction, irreversible damage. Can be diagnosed after only 1 attack - may begin as clinically isolated syndrome (CIS) Tx: Steroids: ↓ inflammation of acute attacks, may ↑ risk of optic neuritis - r/o first. Interferon - beta (Avonex, betaseron) Glatiramer acetate (Copaxone) Natalizumab (Tysabri) - inhibits T cells from leaving circulation and entering CNS = ↓ attacks on myelin. Fatigue: amantadine 100 mg BID. Also modafinil, SSRIs, adderal Motor deficits: K+ channel inhibitor for sx: no tx for lost strength. Spasticity: baclofen, tizanidine, diazepam Urologic: anticholinergics

Encephalitis Inflammation of the brain. Perivascular congestion, hemorrhage, and diffuse inflammatory response disproportionately affects gray matter over white matter. Usually viral prodrome: Fever, myalgias, HA, nonspecific s/sx, rash, lymphadenopathy, hepatosplenomegaly, parotid enlargement (VZV, EBV, CMV, measles, mumps). +/- NVD, cough, sore throat, rash. AMS runs gamut - depends on brain area and pathogen. Seizures common, focal abnormalities.

Dx: ↑ WBC < 250 (bacterial >2,000). Mostly lymphocytes (PMNs early). ↑ protein < 150 (bacterial > 200). Glucose normal (bacterial = low) High mortality rate HSVE, long term motor/mental disabilities 40%. Imaging to r/o brain abscess: MRI = demyelination, edema, necrosis, inflammation. Temporal lobe = HSV, VZV, EBV. Tx: R/o HSV - initiate acyclovir while awaiting blood cx, otherwise no tx: supportive/ICU

Thyroid nodules ↑ with age. Common. Cancer risk factors = head/neck radiation, hx thyroid cancer, hoarseness, age < 20 or > 60, rapid growth/change. Exam findings to suggest cancer = fixed, hard, firm nodules, with painless lymphadenopathy

Dx: thyroid mass Fine needle aspiration, US (FNA if > 1cm, if < 1 cm repeat US in 6-12 mos) Check TSH first. If low = low risk malignancy, if high = high risk malignancy, check T4. If TH low: RAIU to determine function. Hot nodule = made of cells that make TH, so lots of iodine uptake, low risk malignancy, tx hyperthyroidism. Cold nodule = made of cells that don't make TH = low iodine uptake, higher risk malignancy.

Bacterial Meningitis Inflammation of leptomeninges (tissue around brain/spinal cord). MC begins w/infection of sinuses/oropharynx Dx = abnormal # of WBCs in CSF MC infectious: bacteria, viruses, fungi, protozoa. Strep pneumoniae MC in infants/kids/adults Neisseria meningitidis MC in teens/YA (vaccine avail) Group B strep MC in neonates/elderly/chronically ill H. influenza rare d/t vaccine Staph MC following neuro procedures. Pneumococcus, listeria ↑ mortality S/Sx: Classic triad = FEVER NUCHAL RIGITIDY MS CHANGES 95% have 2/3, MC with meningococcal Also: HA (severe), photophobia, NV, focal neuro deficits, seizures (40%) Older adults may present w/only lethargy/obtundation Exam: + Kernig's/Brudzinski signs, papilledema, jolt accentuation of HA, petechial rash (ind. meningococcal). Look toxic. Labs/Dx: Leukocytosis w/left shift CSF = ↑ protein (leakage through tight junctions). LP can cause brain herniation in presence of ICP - do CT first, but can skip if no: seizure/CNS dz hx/papilledema/ms change/focal neuro signs Bacterial: Glucose = ↓(bacteria are eating it) WBCs = ↑↑(100-5,000, PMNs) Protein = ↑↑ Viral: Glucose = normal WBCs = ↑, lymphocytes late

Gram stain: Gram + diplococci → pneumococcal Gram + rods/coccobacilli → listeria Gram neg. diplococci → meningococcal Gram neg. small pleomorphic coccobacilli → H. influenza Imaging: CT best to exclude other causes of ICP. MRI best for ischemia. Enhanced temporal lobes → HSV Enhanced basal region → TB Tx: EARLY INITIATION OF ABX MOST IMPORTANT Empiric = high dose 3rd gen cephalosporins + Vanco + ampicillin if >50 yo, listeriosis, H. flu + acyclovir if HSV - IV acyclovir at 10 mg/kg every 8 hours; transition to orals on discharge; total 10-14 day treatment + doxy if RMSF + anti TB if TB Don't delay antibiotics Ceftriaxone 2 gm, Vancomycin 1 gm, Acyclovir 10mg/kg (ideal wt.) IV dexamethasone ~6 hrs if bacterial Day duration of tx from shortest to longest: Meningococcal 7 H. flu 7-10 Pneumococcal 10-14 Listeria 21

Parkinson's Dz Disorder d/t loss of dopaminergic neurons - substantia nigra neuron damage = dopamine deficiency → unused receptors. Direct pathway excites, but indirect pathway INHIBITS thalamus too much - pathways off balance - indirect > direct. 1% of population, >65 yo, onset early 60s. Etiology unk. Aging only definitive risk factor, genetic predisposition likely Cardinal features: 1) Tremor - unilateral onset, "pill rolling," commonly 1st sx, better w/activity 2) Bradykinesia - slowness or lack of movement (micrographia, quiet monotone speech) 3) Rigitidy - ↑ resistance when moving body part passively - "cogwheeling" - a ratcheting character during ROM - may lead to painful, aching, cramping muscles 4) Postural instability - later onset than tremors and bradykinesia. Shorter stride length → eventual shuffling gait. ↓ arm swing, stooped posture. Pull test for instability - Unified Parkinson's Dz Rating Scale: 0-4. 0 = normal, 4 = can't walk. 1 = walks slowly, 3 = severe, needs assistance Non-motor s/sx: Behavioral = depression, anxiety, personality changes Sensory = aches/pains, RLS, sleep issues Autonomic = constipation, hypotension, sexual dysfunction Exam: Hypophonia, masked facies, ↓ blink rate, bradykinesia w/rigidity, resting tremor - usually starts unilateral and progresses to bilateral. Seborrhea dermatitis of face, involuntary movements, orthostasis, tremors Dx: Clinical: Bradykinesia +: tremor OR rigidity OR postural instability. Response to dopamine diagnostic. No confirmatory lab tests. R/o secondary parkinsonianism (ex. Wilson dz - serum ceruloplasmin - all pts < 40 yo). Genetic testing = Park gene mutation, not routine

Imaging: Spect scan - uses I-ioflupane - presynaptic dopamine transporters - distinguish essential from parkinsonian tremor, may help r/o atypical parkinson's dz. MRI/CT to r/o other d/o Psychotropic drugs, chronic ischemia, vascular changes/infarcts → secondary parkinsonism Tardive dyskinesia - involuntary movements in people taking dopamine ANTAGONIST meds - many Parkinsonian-like features. Often 2ry to: 1st gen psych meds (ex Haldol), oder antiemetics. If drug induced, usually limited to the face. Tx w/Benadryl Tx: Drugs = Levodopa. Improves cardinal sx but NO impact on dz progression. Provides dopamine replacement for years. Treats tremor, bradykinesia, rigidity. Wearing-off phenomenon → dyskinesias - choreiform movements Dopamine agonists: if milder motor sx. Stimulate dopamine receptors in striatum. Reduce "wearing off" when used w/Levodopa - may use as monotherapy, but not good >70 yo d/t SE profile. Anticholinergics help w/tremor, rigidity, but lots of SE. Enhance neurotransmission by improving dopamine-ACH balance in striatum. Atypical antipsychotics - watch EPS Other tx: Surgery for deep brain stimulation (DBS) - high-frequency electrical stimulation of globus pallidus internus (direct pathway) or subthalamic nuclei (indirect pathway). Also ablative surgery, gene therapy (meh), thalalotomy (↓ tremor), pallidotomy (↓ cardinal s/sx), replaced by DBS - not as helpful for gait, speech

Hyperaldosteronism D/o that causes excessive production of aldosterone by zona glomerulosa. Primary = adrenal issue: high aldosterone, low renin S/sx: HTN, cardiovascular events (MC than HTN), muscle weakness (if low K+), HA, psych changes, ↓renin, ↑ alodsterone Causes: 1) Idiopathic bilateral adrenal hyperplasia (MC) 2) Conn syndrome - aldosterone-producing adenoma on one adrenal gland. Lead to ↓ renal flow (d/t hyperaldosteronism)

Labs: Na+ ↑ pH ↑(d/t pH ↑ renal H+ excretion) K+ ↓ or normal Dx: Plasma aldosterone: plasma: renin activity ratio > 20 strongly suggestive of hyperaldosteronism. CT adrenals to r/o adenoma. Tx: Adrenalectomy. Spironolactone. HTN management.

Pheochromocytoma Tumor of adrenal glands that causes them to produce too much catecholamines. S/sx: 5 P's: Paroxysmal, pain (HA), pressure (HTN), palpitations, perspiration. Cause of 2ry HTN less than 1% of the time.

Labs: ↑ 24 hr. metanephrines/plasma metanephrines. Urine catecholamines Imaging: MRI abdomen > CT 10% are malignant tumors of the adrenal medulla Tx: a/b blockade Definitive = adrenalectomy

Neoplastic Thyroid Disease 5 types: Papillary (MC): Previous exposure to radiation: Painless asymptomatic mass, dysphagia/dyspnea/hoarseness when advanced. Tx = surgery, radioactive iodine.

Medullary: C-cells in thyroid. Tumors secrete calcitonin. FNA. Poor 131 uptake. 50% 10 year survival. Cure < 20%. Tx = thyroidectomy, median lymph node dissection. MC in MEN. Hurthle cell: From follicular cells. No 131 uptake. FNA. Lymphatic spread. Tx = thyroidectomy. Anaplastic: Female > male. 131 uptake, FNA. 100% mortality. Good prognosis, +131 uptake. Follicular: Iodine deficient areas, more aggressive. MC in females. NO FNA. Mets MC → bone. +131 uptake. Tx = thyroidectomy

Prediabetes Glucose levels don't meet criteria for DM but are too high to be normal. Increases risk for CVD. Native Americans highest prevalence.

Metabolic syndrome 3 of the following: Obesity (waist-gender) Glucose impairment ↑ BP High tryglicerides Low HDL (gender)

Viral meningitis: Inflammation of leptomeninges (tissue around brain/spinal cord). MC begins w/infection of sinuses/oropharynx Dx = abnormal # of WBCs in CSF May also cause encephalitis. Enterovirus MC. Labs/Dx: CSF: Glucose = normal WBCs =↑ (10-300) , lymphocytes late Protein = ↑ HSV 1 or 2 = ↑ CSF red count. *85% with HSV-2 have genital lesions 3-12 days prior* HSV-1 manifests as encephalitis - high mortality S/sx: Rash, sore throat, diarrhea, joint aches, HA, +/- prodrome, MC late summer/early fall. Aseptic meningitis: Clinical and labs show meningitis, but no PMNs, neg. gram stain and blood cx. MC viral. Also meds, malignancy, autoimmune. Fungal = cryptococcus (esp HIV). TB = subacute, MC in older, debilitated, HIV. Syphillis, lyme dz. Tx aspetic meningitis: elderly, immmune compromised, prior abx = treat as bacterial Viral meningitis + HIV = mono-like syndrome, usu. resolves w/o tx

Noninfectious Causes of Aseptic Meningitis: Malignancy: hematologic malignancies often seed CNS, esp large cell lymphomas & acute leukemia Solid tumors: breast, lung, melanoma, GI Dx: cytology shows malignant cells in CSF Systemic processes: SLE, other collagen-vascular disease Inflammatory processes primarily involving the CNS Drug hypersensitivity Drug induced = unusual adverse type IV rxn to: NSAIDs, abx (*Bactrim*), IV immunoglobulins, cetuximab, antiepileptics. S/sx resolve after drug removal Pre-aseptic meningitis: HA, fever, photophobia. Diffuse maculpapular exanthem, mildly ill = enterovirus, HIV, or syphillis. Parotitis = mumps in unvacc. Genital lesions = HSV-2. Asymmetrical flaccid paralysis = West Nile If suspect HSV-1 and -2, West Nile, enterovirus, VZV send CSF out for PCR eval Prevention: Vaccination for meningococcus A, C, W, Y, serogroup B @ age 11-12, booster @ 16. For military recruits in barracks, HIV, asplenic/spleen damage, college students. Past exposure/household contacts = Rifampin 600 mg BID x 2 days Single dose ciprofloxacin 500 mg 5-10% of adults are asymptomatic nasopharyngeal carriers flouroquinolones, ceftriaxone eradiate meningicocci from nasopharynx

Delirium Common in 65+, older hospitalized patients (esp ICU, post-op). Disturbance of consciousness (↓ clarity of awareness of environment) w/ ↓ ability to focus, sustain, or shift attention. Change in cognition (memory deficit, disorientation, language disturbance) or development of perceptual disturbance that is not explained by a pre-existing/established/evolving dementia. Develops over a short time, tends to fluctuate during the day, caused by direct consequences of a general medical condition.

Often d/t meds - esp abx. Risk factors = cognitive impairement/dementia, illness, ↑ comorbidity, functional impairment, ↑ age, CKD, dehydration, malnutrition, vision/hearing impaired. Immobility/restraints can precipitate. Treat underlying cause, keep family w/pt. Have glasses/hearing aids/interpreters available. Tx: Haloperidol or lorazepam, seroquel for sleep (monitor QTI)

Type I Diabetes Chronic state of hyperglycemia d/t: 1) Deficiency of insulin secretion 2) Deficiency of insulin action 3) or both of the above 5-10% type I Causes = MC = viral infection or autoimmune dz + genetic predisposition → development of autoantibodies against B cells → absolute insulin deficiency d/t B cell destruction. May also be caused by genetic defects, steroids, pancreatic d/o, LADA S/Sx: Polyuria/dipsia. Acute, profound weight loss. NV, abd pain. Lethargy, tachypnea, DKA. DKA criteria: Glucose > 250 mg/dL ph < 7.3 HCO3- < 18 mEq/L + serum ketones Dx: Prediabetes = A1C 5.7 - 6.4% FBG 100-125 mg/dL OGTT 149-199 mg/dL RPG none Tx: Insulin: multiple daily injections of prandial and basal, or continous SQ infusion via pump. Also pancreatic islet cell transplant. Type II Diabetes Chronic state of hyperglycemia d/t: 1) Deficiency of insulin secretion 2) Deficiency of insulin action 3) or both of the above 90-95% type II Latent autoimmune diabetes of adult - thin, 20s-30s, look like a type I and act like a type II. Obesity MC cause.

Risk factors: FH, *obesity/overweight*, *HTN*, *dyslipidemia*, physical inactivity, hx of gestational DM, PCOS. Causes: Genetic predisposition + environment + unhealthy lifestyle = insulin resistance Diabetes = A1C ≥ 6.5% FBG ≥ 126 mg/dL OGTT ≥ 200 mg/dL RPG ≥ 200 mg/dL S/Sx: Asymptomatic, fatigue, blurred vision, parasthesias, candida infections, UTIs, skin infections HHS: hyperosmolar hyperglycemic state = high glucose levels (>1,000), AMS, coma, can lead to permanent neuro deficits Screening: Everyone @ 45, then q 3 yrs Everyone w/sx, risk factors Tx: Diet and exercise *Weight control* Oral meds Insulin Goals: A1C < 7% (varies) BP < 140/90 LDL < 100 mg/dL Complications: Retinopathies (microaneurysms, hemorrhages, exudates), nephropathies (30-40% all DM1 in 20 yrs, 15-20% all DM2), neuropathies (peripheral, autonomic), CAD, CVA, PVD Tx: Metformin, SGLT-2 inhibitors, GLP-1 agonists, DDP-4 inhibitors, TZDs, sulfonyureas, alpha glucosidase inhibitors

Hypothyroidism ↓ levels of thyroid hormone MC = primary: gland failure → low T4, high TSH Also secondary: d/t pituitary TSH deficiency Tertiary: hypothalamic deficiency of TRH Hashimoto thyroiditis MC primary: autoimmune inflammatory d/o that causes autoantibody destruction of thyroid tissue. 95% women, clusters in families. Subclinical hypothyroidism: ↑ TSH but normal T4, so no s/sx. Risk of progression to clinical hypothyroidism Myxedema coma: severe hypothyroidism w/high mortality rate. Precipitated by acute illness, trauma, cold intolerance. S/sx: impaired mentation, hyponatremia, hypoglycemia, hypothermia, respiratory depression. Tx = slow warming, levothyroxine, hydrocortisone

S/Sx: Depends on age @ onset. Infancy = defective physical, mental development (cretinism). Often d/t low iodine, also in utero with hypothyroid mothers. Children = retarded growth, ↓ school performance. Adults = apathy, fatigue, cold intolerance, coarsening of facial features, tongue thickening, deepening of voice, ↓ CO, hair loss, depression, thyroid enlargement,dry skin, HTN, expressionless face Dx: TSH most sensitive, T4 Tx: T4 (levothyroxine) - doesn't cause rapid ↑ in T3 that is assoc. with ↑cardiac risk

Diabetes insipidus Either deficiency of or loss of sensitivity to ADH. 2 types: 1) Central = absolute/relative deficiency of ADH. Causes: pituitary adenomas, trauma, autoimmune, infections, genetic defects 2) Nephrogenic = renal insensitivity to ADH → ↓ collecting duct permeability. Causes: meds (*Lithium 55%), chronic disease

S/Sx: Polyuria, polydipsia, +/- hypovolemia. Labs: ↓ urine osmolarity, ↑ serum osomolarity, ↑ Na+, normal BGL. Dx: Water deprivation test. + = continuous urine production when fluid-deprived Tx: Central = desmopressin (DDVAP) Nephrogenic = gentle diuretics (HCTZ), DDVAP`

Pituitary adenoma Tumor of pituitary gland. MC prolactinoma. May produce visual field disruption → bitemporal hemianopsia (bilat loss of periph. vision). Hyperprolactinemia causes: hypothyroidism, dopamine antagonists, SSRIs, estrogen, stress, exercise

S/sx: Amenorrhea, milk breast discharge, HA, visual field loss. ♀ present early, ♂ present late Dx: MRI of pituitary Labs: ↑ prolactin. Tx: Dopamine agonist. < 10 mm = observe, > 10 mm = surgery

Tension Headache Holocranial HA w/o NV that doesn't worsen w/activity. +/- photo/phonophobia. MC type of HA, ♀ MC, white > AA, western hemisphere. Chronic = HA ≥ 15 days/mo. Genetic like, influenced by environment. ↑ muscle tenderness → activates peripheral nociceptor → pericranial muscle tenderness (usu only abnormal finding)

S/sx: Mild/moderate, bilateral, no throbbing, no assoc. s/sx. Dull, band-like pressure, heavy weight, head fullness Tx: Tylenol, NSAIDs, naproxen, ketoprofen. Prevention: Amitryptiline, nortriptyline, fluoxetine, PT, acupuncture, muscle relaxers

Complex Regional Pain Syndrome Chronic pain d/o usually affecting a distal unilateral extremity. Follows trauma to affected area. S/sx disproportionate to usual course of healing expected for predisposing injury. Central pain syndrome: changes alter brain/spinal cord's ability to perceive pain normally: stress, h/o depression, physical/psychological trauma all predispose one to changes.

S/sx: STAMP: Sensory = allodynia, hyperalgesia Trophic: skin, hair, nail changes Autonomic: sweating, swelling, edema Motor: atrophy, weakness Pain Tx: Pain management referral, education, PT/OT, psychosocial/behavioral tx, injections, nerve blocks Drugs: NSAIDs, anticonvulsants, TCAs, lidocaine (same as DPN). Avoid opioids - can increase their sensitivity to pain

Addison's Disease Chronically low levels of cortisol. Primary adrenal insufficiency: bilateral destruction of adrenal cortex. MC in US = autoimmune. Also infectious (TB), neoplasms, AIDS. Need 90% bilateral destruction for s/sx onset, s/sx MC d/t corticosteroid withdrawal, also infection. S/sx: Fatigue, weakness, muscles aches, weight loss, hypotension, NVD, sparse axillary hair, ↑ skin pigmentation, esp over creases/pressure areas

Secondary adrenal insufficiency = low cortisol levels d/t pituitary not secreting ACTH. Also a lack of CRH from the hypothalamus Lab results Addison's: AM ACTH/K+/renin ↑, Na+/glucose/AM cortisol ↓(<3 mg/dL @ 8 am diagnostic) Testing: 1) Synthetic ACTH stimulation test (primary adrenal insufficiency) 2) Serum adrenal antibodies 3) CT adrenals: size, masses Tx = 4 S's: Steroids Sugar Salt Search for cause Lifetime of tx with hydrocortisone and mineralcorticoids

Cluster headache Part of trigeminal autonomic cephalgias ♂ > ♀, 20-30 yo Strong family link Rare < 10 yo S/sx: Unilateral HA with ipsilateral lacrimation, conjuctival injection, tearing. +/- nasal congestion, rhinorrhea, ptosis, miosis, flushing, eyelid edema, restlessness. Horner's syndrome = miosis, partial ptosis, anhidrosis (inability to sweat) Chronic = attack w/o remission ≤ 1 month for at least 1 year Paroxysmal hemicrania: unilateral pain lasting 2-30 mins 5x/day with 1+ autonomic feature Hemicrania continua: unilateral HA, occurs daily w/o pain-free periods with 1+ autonomic feature Prevent hemicranias with indomethacin

Short unilateral neuralgiform HA: unilateral, orbital, supraorbital, temporal pain w/conjunctival injection and tearing - 5-240 seconds, 3-200x/day "suicide HA" Dx: Recommend imaging to r/o lesions/infection/neoplasm Tx: 100% O2 7-10 LPM x15-30 mins Sumatriptan, Zolmitriptan, dihydroergotamine Prevention: verapamil, lithium, corticosteroids, anticonvulsants - start @ onset. Also valproic acid, topiramate, melatonin, gabapentin

Stroke/CVA Stroke = > 24 hrs, infarction TIA = minutes-hours, NO infarction, but 50% have a stroke w/in 24-48 hrs Risk Factors: Modifiable = HTN, ↑ lipids, CAD, hypercoagulability, DM. Non-modifiable =age, ♀/♂, prior stroke, race, family hx, migraines Behavioral = smoking, ETOH, obesity, ↓ physical activity, drug use (illicit), oral BCP + smoking Patho: Interruption of blood flow → ischemia = ↓ ATP production; malfunction of cells' ionic pumps →1) cytotoxic edema = influx of fluid into brain cells or 2) vasogenic edema = influx of fluid into interstitial space Death to brain tx in 4-10 mins w/0 blood flow. < 16-18 mL/100g of brain tissue = infarction in < 1 hr. Bigger area involved = bigger deficit. Ischemic penumbra = area of infarcted tissue that is salvageable if reperfused. Core irreversibly damaged. Benign oligemia - decreased flow but not at risk of infarction. MC stroke = ischemic. Thrombotic (large vessel, lacunar) or cardioembolic (ex. a-fib). The rest hemorrhagic (intracerebral, subarachnoid - aneurysm, AVM). MC involved artery = middle cerebral Common stroke s/sx: hemiparesis, speech disturbance, sensory loss, vision loss, ataxia Large vessel s/sx: Visual loss/field deficit (think carotid) Aphasia only if dominant sphere involved (MC left) Weakness, ataxia (think cerebellar) Small vessel/lacunar (MC) s/sx: Pure motor, pure sensory = contralateral. MC lacunar stroke. Mixed (motor & sensory). Previous hx = HTN, DM, atherosclerosis. Prognosis better than large vessel Embolic stroke: MCA MC, d/t: cardiac, carotid arteries, aortic atheroma Hemorrhagic stroke: "worst HA of my life." Meningeal signs: NV, nuchal rigidity, seizure suggests subarachnoid hemorrhage. Prominent ↓ LOC. Severe HTN. Risk factors = HTN, bleeding d/o, AA, AVM, ETOH. HIGHER mortality than ischemic. MCA stroke = UE. S/sx: contralateral weakness (face/arm > leg), contralateral sensory loss, aphasia if dominant hemisphere. ACA stroke = LE. S/sx: usually w/MCA stroke. Contralateral motor and sensory loss: leg < face/arm. PCA stroke sx/s: contralateral visual field defect. Mild contralateral motor and sensory defect. "D" symptoms: dysarthria, diplopia, dizziness (VERTIGO), dysphagia, depressed LOC, difficulty: walking, hearing

Stroke screen = FAST: face, arms, speech, time of onset. Expressive aphasia = Broca's area, receptive aphasia = Wernicke's area. Focus on BP w/vitals Dx: Non-contrast CT/MRI read by a neuroradiologist, labs for cardiac enzymes, CBC, clotting factors, BMP, coags, HIV, syphilis serology, carotid US Tx: Goal = door to CT in < 25 mins. Bleed = BP control, reverse risk of bleed (coumadin), call neuro consult. No bleed = thrombolysis (tPA), endovascular intervention (better for big bleeds), ASA (24 hrs post tPA), VTE prophylaxis (heparin), swallow study (aspiration pneumonia) Ischemic stroke = tPA (altaplase) w/in 3-4.5 hours of symptom onset Treat BP >220/120, end organ damage (CHF, aortic dissection, hypertensive encephalopathy) in everyone (labetolol or nicardipine). Treat all tPA candidates with BP >185/110, after tPA = <180/105 BP goals: Ischemic w/no thrombolysis = treat if BP > 220, goal 15% reduction in 1st 24 hours Hemorrhagic = treat if BP > 140, goal variable. NO ASA for hemorrhagic, yes for ischemic but delay for 24 hours if tPA Primary prevention: Most important modifiable risk factor for preventing both types of strokes = *HTN* Risk factors: A-fib, mitral stenosis, prosthetic cardiac valve, recent MI, thrombus in LV or LA appendage, atrial myxoma, dilated cardiomyopathy. Secondary prevention: antiplatelets (ASA, clopidogrel, dipyridamole), warfarin (cardioembolic stroke prevention), statins (↓risk for fatal/nonfatal strokes) *Better to prevent a stroke than treat one!*

Osteoporosis A skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength primarily reflects the integration of bone quality and bone density. Primary: due to declining age and declining gonadal function Secondary: due to other medical conditions / medications Bone density is determined by peak bone mass and subsequent of bone loss Bone quality refers to bone architecture, turnover, mineralization, and accumulation of damage The World Health Organization (WHO) defines osteoporosis as a bone mineral density value more than 2.5 standard deviations below the mean for young, healthy, white women Non-modifiable risk factors: Family history of osteoporosis and/or fracture Older age Being female (but men get osteoporosis too) Ethnicity (esp. Caucasian, Asian or Hispanic) Menopause, especially at an early age (<45) Being small and thin; Scandinavian Modifiable risk factors: Smoking Low lifetime calcium and/or vitamin D intake Lifetime lack of physical activity Excessive alcohol use Underweight for height (low body mass index) when caused by unhealthy diet or excessive exercise, rapid weight loss Hormonal imbalance (sometimes modifiable) PTH - Stimulates osteoclastic bone resorption indirectly to release calcium from bone. Stimulates the renal production of 1,25 dihydroxyvitamin D to increase calcium absorption from the intestine. Enhances renal phosphate and bicarbonate excretion. 1,25 dihydroxyvitamin D (cholecalciferol) - Promotes gastrointestinal absorption of calcium and phosphorus. Necessary for bone mineralization The Most Devastating Consequence of Osteoporosis = hip fx Biggest risk factor = prior fracture Bone DensitometryCentral Dual X-ray Absorptiometry gold standard Measures the amount of mineral (such as calcium) in a specific area of bone Can detect osteoporosis before a bone breaks Helps predict chances of fracturing in the future Helps determine need for osteoporosis treatment Indicated for: Women >65 regardless of risk factors Women <65 if 1 or more risk factors Men with clinical manifestations of low BMD (osteopenia on x-ray, hx low trauma fractures, loss of >1.5" height) and those with risk factors No routine BMD testing is recommended for children, premenopausal women or men under age 50

T-scores: normal = -1.0 and above. Osteopenia = -1.0 - -2.5. Osteoporosis = -2.5 and lower Repeat q 2-3 years. Prevention: Maximize Peak bone mass - children and adolescents Nutrition, physical activity, normal body weight, avoid smoking and EtOH Minimize Bone loss - adults Weight bearing exercise (30 min most days) Adequate nutrition (protein, calcium and vitamin D Smoking cessation Moderate EtOH Fall prevention Tx: Calcium supplements - If cannot take calcium with food or if take acid blocking medication - calcium citrate recommended, 1200 mg. Vitamin D 600-800 IU Physical activity, smoking cessation Offer tx to men and women age 50+ who: Have a hip or vertebral (clinical or morphometric) fracture T-score ≤ -2.5 at the femoral neck or spine after exclusion of secondary causes T-score between -1.0 and -2.5 at the femoral neck or spine and a 10-year probability of a hip fracture ≥ 3% or a 10-year probability of a major osteoporosis-related fracture Clinicians judgment and/or patient preferences may indicate treatment for people with 10-year fracture probabilities above or below these levels Offer tx with bisphosphonates (alendronate, risedronate, zolendronic acid), or denosumab to reduce risk for hip and vertebral fracture in women with osteoporosis Tx osteoporotic women for 5 yrs Offer tx with bisphosphonates to men with clinically recognized osteoporosis to reduce risk of vertebral fx. Oral bisphosphonates: Oral formulations have poor absorption and complicated protocols for ingestion May cause GI side effects, esophagitis. Contraindicated in severe renal impairment, hypocalcemia, esophageal disorders Black Box warning for osteonecrosis of the jaw (ONJ). Need to stop taking of they are having a dental procedure done to avoid ONJ. Rare risk atypical femur fx No BMD testing in 5 yr tx period Do not recommend estrogen or SERMS Make decision about treating osteopenic women 65+ with high fx risk after assessing pt preference, fx risk, benefits, harms and cost.

Cerebral aneurysm Focal dilation of arterial wall. Risk factors: Smoking, alcohol, family hx of subarachnoid hemorrhage, connective tx d/o (ex. Marfan's), previous SAH

TIA Stroke s/sx= minutes-hours, NO infarction, but 50% have a stroke w/in 24-48 hrs Same eval as stroke: CT, MRI, echo, labs. If resolution of s/sx: begin 2ry stroke prevention: lifestyle mod, ASA + dipyridamole, statin. S/sx ongoing/disabling: consider tPA or mechanical thrombectomy w/in 3-4.5 hrs of sx onset

Thyroid goiter Generalized thyroid enlargement, MC thyroid disease. Increase in size not equal to increase in function. Causes = Hashimoto's, Grave's, iodine deficiency (MC worldwide), nodule, error in hormone synthesis.

Thyroiditis Acute: Painful, swollen thyroid, fever, skin erythema d/t bacteria (strep, staph), usually from thyroglossal fistula or anatomical variant. Tx = abx, drainage, FNA Subacute: glandular swelling, tenderness, often following URI. Tx = supportive, NSAIDs, steroids Chronic: Hashimoto's and Riedel's - benign inflammatory thyroid enlargement w/thyroid fibrosis = large, painless thyroid

Tourette's Neuropsychiatric disorder with onset in childhood, characterized by multiple motor tics and at least one vocal (phonic) tic. These tics characteristically wax and wane, can be suppressed temporarily, and are typically preceded by an unwanted urge or sensation in the affected muscles. Some common tics are eye blinking, coughing, throat clearing, sniffing, and facial movements. Tourette's does not adversely affect intelligence or life expectancy. While the exact cause is unknown, it is believed to involve a combination of genetic and environmental factors. In most cases, medication for tics is not necessary. Education is an important part of any treatment plan, and explanation and reassurance alone are often sufficient treatment.[2][5] Many individuals with Tourette's go undiagnosed or never seek medical care. Among those who are seen in specialty clinics, attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) are present at higher rates. These co-occurring diagnoses often cause more impairment to the individual than the tics; hence, it is important to correctly identify associated conditions and treat them.

Tics = quick, non-rhythmic movements or vocalizations that happen over and over, not associated with ETOH or Huntington's dz. 3 criteria: 1) # of tics - mutiple motor tics and at least 1 verbal tic 2) Duration of tic d/o - need to persist for at least 1 yr 3) Age when tics started - need to have started before 18 yo Tics: Simple = short in duration: eye blinks, throat clearing Complex = longer in duration, combo of simple tics Echopraxia = repeat movements of others Copropraxia = obscene gestures Echolalia = repeating last word heard Palilalia = repetition of last word said Coprolalia = repeated inappropriate words Most severe before puberty and decrease after. May have an aura before a tic. Worse w/anxiety/excitement/exhaustion Tx: Behavioral therapy, habit reversal training, reduce anxiety/depression. Meds only for severe cases: Antipsychotics (haldol, risperidone), antiepileptics. ADHD meds. Botox injections to tic site to minimize appearance

Epilepsy/Seizure Seizure = sudden, abnormal firing of cortical neurons in the brain resulting in altered perception or behavior. Epilepsy = any condition of unprovoked recurrent seizures, at least 2 more than 24 hours apart. Family hx strongest risk factor for childhood epilepsy Tonic phase: phase of seizure immediately following loss of consciousness → rigidity, sudden arrest of respiration. May include incontinence, tongue biting, or aspiration, assoc. with postictal confusion. Prolactin commonly elevated after seizure Postictal period = time immediately after the seizure during which there is an altered LOC. Drowsiness, confusion, HA. Generalized seizures. Tonic-clonic seizure AKA grand mal seizure. Tonic = extension, clonic = flexion. Tongue-biting pathognomonic for seizure activity Focal seizure = seizure involving a restricted part of the brain; may evolve to a bilateral convulsive seizure. No LOC changes Absence/petit mal seizure = lapses of consciousness assoc. w/postictal confusion. Can be induced with up to 3 mins of hyperventilation. Usu. normal PE Tx absence seizures = ethosuximide (Zarontin), valproic acid, clonazepam Status epilepticus = continuous seizure activity that lasts > 5 mins, or intermittently for at least 30 mins. MC cause noncompliance w/seizure meds.

Tx status epilepticus = benzos. Ex lorazepam 0.1mg/kg @ 2mg/min as loading dose, max 4 mg/dose, then second dose in 10-15 mins if ness. Max 8 mg/12 hrs Simple-partial seizure = focal motor sx, no LOC change. Twitching that spreads to the rest of the area, followed by weakness Atonic seizures = epileptic drop attacks Automatisms = repetitive mouth movements, chewing, gulping, spitting, mumbling, hand movements (grasping, fumbling) Acute benign febrile seizure = typically age 3-36 months almost always < 5. Genetic predisposition, usually only occurs 1-2x. Unusual in under 3 months - suspect meningitis Seizure causes: Electrolyte d/o (Hyper/hyponatremia, hypocalcemia, hypomagnesemia) Also brain tumors, stroke, ETOH withdrawal, alzheimers, CNS infection, sleep deprivation, stress/anxiety, fever, drugs, hypoxemia, head trauma, uremia, hyperthyroidism, hypoglycemia Progresterone → increases seizure threshold, reduces likelihood of seizure Estrogen → decreases seizure threshold, increases likelihood of seizure (Progesterone protective, estrogen evil) Pt must be seizure-free for 6 mos to be able to drive, 12 mos for chauffers Tx: Bupropion - lowers seizure threshold Dx first-time seizure: CBC, glucose, electrolytes, prolactin, tox screen, BUN/Cr, AST/ALT, CPK, TSH, carboxyhemoglobin

Myasthenia gravis Exercise-induced fatiguability hallmark. Usually young, ♀>♂. Autoimmune d/o of postsynaptic membrane @ neuromuscular junction → destruction of Ach receptors = muscle weakness. Any age, fatiguable muscle weakness/dysphonia. Ptosis, EOM fatigue common. Face/neck/extremities, respiratory muscles Dx: Sx improve immediately w/trial of an acetylcholinesterase inhibitor. Cold pack over the eye improves ptosis = MG Labs/tests: Serum anti-AchR antibodies positive in 80-90% of generalized MG (50% with ocular sx only) Anti-muscle-specific tyrosine kinase (MUSK) ab - + in 70% of AChR seronegative pts CT, MRI → thymus gland abnormality (thymoma)

Tx: Mild dz, mild s/sx: none, otherwise pyridostigmine (cholinesterase inhibitor) - add corticosteroids if unresponsive to inhibitor Moderate dz: pyridostigmine + immunosuppressant (steroids, cyclosporins, tacrolimus). Thymectomy (adjunct) - pts with thymoma = any age, pts w/o thymoma = 15-55 MG crisis: severe weakness, resp failure (not common): intubation, vent, plasma exchange/IV immunoglobulin

Concussion MC in 0-4 yo, 15-19 yo, >65 yo Adults 75+ = highest TBI-releated hospitalizations and death rates. TBI occurs w/head injury d/t contact and/or accel/decel forces. MC MOI = falls (1), struck by/against (2), MVCs (3). Mild GCS 13-15 approx 30 mins after injury. Rapid onset short-lived impairment of neuro function that resolves spontaneously - can persist minutes-hours. Typically functional, not structural. Cortical contusions d/t coup-countrecoup. Disruption of axonal neurofilament organization impairs axonal xport → axonal swelling, degeneration, transection. S/sx: Confusion, amnesia, repetitive ?s, +/- LOC. Later = HA, vertigo/imbalance, mood changes, sleep disturbances. Vacant stare, delayed verbal response, disorientation, inability to focus. Post traumatic seizures can occur w/in 1st week of injury, most w/in 24 hrs. +/- subdural hemorrhage

Tx: Observation vs head CT Peds: PECARN algorithm for CT or not - depends on MOI, presentation Imaging if: suspected skull fx, raccoon eyes, intraorbital bruising, battle's signs, hemotympanum, CSF leak, rhinorrhea, 2 episodes of emesis, > 65 yo, significant MOI Second impact syndrome -2nd concussion that occurs before the sx of a previous one have resolved Chronic traumatic encephalopathy - memory/impulse control loss, depression, eventual dementia King-Devick test - concussion screening test Post-concussive syndrome: Common sequelae of TBI - HA, dizziness, neuropsych symptoms, cognitive impairment last weeks-years. Common w/repetitive injuries, 80% of mild TBIs. Manage sx, neuropsych eval, otolaryngology for persistent vertigo

Diabetic Peripheral Neuropathy Damage to PNS 2ry to poorly controlled DM → sensory impairment, MC in distal extremities. D/t excess glucose, also HTN, smoking, ETOH, ↑ lipds S/sx: pain, paresthesias (burning/tingling/numbness), extreme sensitivity to touch, sensory loss, balance loss, distal motor symptoms. Dx: monofilament testing, vibratory sensation Prevention: Improve glycemic control, education, foot care. Early detection crucial to avoid amputation

Tx: Pain management: pregabalin 1st line. Also anticonvulsants (inhibit post-synaptic nerve transmission → ↓ pain signals): gabapentin, phenytoin TCAs/SSRIs/SNRIs: alter how the brain registers pain. Topical = lidocaine Opioids Refer: podiatry, wound care center, PT/OT

Acromegaly Excessive growth of hands, feet, jaw, internal organs. D/t excess GH secretion - pituitary adenoma. (Gigantism = excess GH in childhood) Often unrecognized until middle age - old photo can confirm changes S/Sx: Tall, coarse facial features, large jaw/tongue, deep voice, large hands/feet, HTN, cardiomegaly, CHF, acanthosis nigracans, doughy texture Dx/Labs: ↑ GH. IGF-1 best screening test: >5x normal. Oral glucose suppression test - glucose won't suppress GH

Tx: Surgery best 1st, then pituitary irradiation if surgery fails. Also dopamine agonists, GH receptor agonists work better (ex. somatostatin analogues): bind to receptors on the GH producing cells in pituitary gland and ↓ GH production.

Huntington Disease Autosomal dominant, neurodegenerative disease. Onset 35-50 yo. Psych s/sx, chorea - involuntary motion of hips/legs/trunk hallmark. Gait disturbance. Cognitive decline, dementia - predictive of prognosis. Cause unknown. Atrophy of cuadate nucleus and putamen (striae), ↓ in GABA-ergic neurons in striatum → reduced inhibition of thalamus → ↑ thalamus output to cortex = ↑ cortical stimulation to muscles = ↑ involuntary movement. Opposite of Parkinson's

Tx: Counseling: genetic, behavioral Meds: Tetrabenazine, antipsychotics, SSRIs: all ↓ chorea movements

Altered LOC Drowsy = lethargy, ↓activity, loss of eye contact Confusion = cognitive abilities slowed/impaired Delirium = altered perception, disordered thinking, delusions Obtundation = less alert, disinterested in environment Stupor = stimulation required for arousal Coma = pt does not respond to stimuli

Use AEIOU-TIPS mnemonic to suss out a cause of AMS. AMS workup based on: Brain fuel (fingerstick, O2 sats, +/- thiamine) Metabolic: CBC, NH3, ABG, TSH Toxins: CO, ETOH, urine tox, EKG Infections: CXR, UA, +/- LP Structural: Head CT Coma cocktail: dextrose, O2, narcan, thiamine (before dextrose)

Bell's Palsy AKA idiopathic facial paralysis (IFP). acute, unilateral, peripheral, lower-motor-neuron facial nerve paralysis that gradually resolves over time in 80-90% of cases. Most common cause of unilateral facial paralysis. It is one of the most common neurologic disorders of the cranial nerves. In the great majority of cases, Bell palsy gradually resolves over time, and its cause is unknown, although the disorder appears to be a polyneuritis with possible viral, inflammatory, autoimmune, and ischemic etiologies. Increasing evidence implicates herpes simplex type I and herpes zoster virus reactivation from cranial-nerve ganglia. more common in adults, in people with diabetes, and in pregnant women. S/sx:Acute onset of unilateral upper and lower facial paralysis (over a 48-hr period) Posterior auricular pain Decreased tearing Hyperacusis Taste disturbances Otalgia Weakness of the facial muscles Poor eyelid closure Aching of the ear or mastoid Tingling or numbness of the cheek/mouth Epiphora Ocular pain Blurred vision Flattening of forehead and nasolabial fold on the side affected by palsy When patient raises eyebrows, palsy-affected side of forehead remains flat

When patient smiles, face becomes distorted and lateralizes to side opposite the palsy Dx:Otologic examination: Pneumatic otoscopy and tuning fork examination, particularly if evidence of acute or chronic otitis media Ocular examination: Patient often unable to completely close eye on affected side Oral examination: Taste and salivation often affected Neurologic examination: All cranial nerves, sensory and motor testing, cerebellar testing Tx: Corticosteroid therapy (prednisone) [6, 7] Antiviral agents [6, 8] Eye care: Topical ocular lubrication is usually sufficient to prevent corneal drying, abrasion, and ulcers [9] Surgical options Surgical treatment options include the following: Facial nerve decompression Subocularis oculi fat lift Implantable devices (eg, gold weights) placed into the eyelid Tarsorrhaphy Transposition of the temporalis muscle Facial nerve grafting Direct brow lift

Hyperparathyroidism A. General characteristics 1. One or more glands produce inappropriately high amounts of PTH relative to the serum calcium level. 2. Most common cause of hypercalcemia in the outpatient setting. B. Causes 1. Adenoma (80% of cases)—majority involve only one gland 2. Hyperplasia (15% to 20% of cases)—all four glands usually affected 3. Carcinoma (<1% of cases) C. Clinicalfeatures 1. "Stones" a. Nephrolithiasis b. Nephrocalcinosis 2. "Bones" a. Bone aches and pains b. Osteitis fibrosa cystica ("brown tumors")—predisposes patient to pathologic fractures 3. "Groans" a. Muscle pain and weakness b. Pancreatitis c. Peptic ulcer disease d. Gout e. Constipation 4. "Psychiatric overtones"—depression, fatigue, anorexia, sleep disturbances, anxiety, lethargy 5. Other symptoms: a. Polydipsia, polyuria b. HTN, shortened QT interval c. Weight loss D. Diagnosis 1. Laboratory a. Calcium levels (hypercalcemia)—When calculating calcium levels, be aware of albumin levels. Calculate the ionized fraction or get an ionized calcium level. b. PTH levels • Should be elevated relative to serum calcium level

• Note that in the presence of hypercalcemia, a normal PTH level is "abnor- mal" (i.e., high) because high calcium levels suppress PTH secretion. c. Hypophosphatemia d. Hypercalciuria e. Urine cAMP is elevated. f. Chloride/phosphorus ratio of >33 is diagnostic of primary hyperparathyroidism (33-to-1 rule). Chloride is high secondary to renal bicarbonate wasting (direct effect of PTH). 2. Radiographs a. Subperiosteal bone resorption (usually on radial aspect of second and third phalanges) b. Osteopenia E. Treatment 1. Surgery is the only definitive treatment, but not all patients require it. If the patient is over 50 years of age and is asymptomatic (with normal bone mass and renal function), surgery may not be needed. a. Primary hyperparathyroidism due to hyperplasia—All the four glands are removed. A small amount of parathyroid tissue is placed in the forearm muscle (prevents the need for re-exploration of the neck if hyperplasia recurs postop- eratively) to retain parathyroid function. b. Primary hyperparathyroidism due to adenoma—Surgical removal of the ade- noma is curative. c. Primary hyperparathyroidism due to carcinoma—Remove the tumor, ipsilateral thyroid lobe, and all enlarged lymph nodes