["530 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology Intracranial hemorrhage Epidural hematoma Rupture of middle meningeal artery (branch A B of maxillary artery), often 2\u00b0 to skull fracture C D (circle in A ) involving the pterion (thinnest E F area of the lateral skull). Might present with G H transient loss of consciousness \u008e\u00a0recovery (\u201clucid interval\u201d) \u008e\u00a0rapid deterioration due to hematoma expansion. Scalp hematoma (arrows in A ) and rapid intracranial expansion (arrows in B ) under systemic arterial pressure \u008e transtentorial herniation, CN III palsy. CT shows biconvex (lentiform), hyperdense blood collection B not crossing suture lines. Subdural hematoma Rupture of bridging veins. Can be acute (traumatic, high-energy impact \u008e\u00a0hyperdense on CT) or chronic (associated with mild trauma, cerebral atrophy, \u008f\u00a0age, chronic alcohol overuse \u008e\u00a0hypodense on CT). Also seen in shaken babies. Crescent-shaped hemorrhage (red arrows in C and D ) that crosses suture lines. Can cause midline shift, findings of \u201cacute on chronic\u201d hemorrhage (blue arrows in D ). Subarachnoid Bleeding E F due to trauma, or rupture of hemorrhage an aneurysm (such as a saccular aneurysm) or arteriovenous malformation. Rapid time course. Patients complain of \u201cworst headache of my life.\u201d Bloody or yellow (xanthochromic) lumbar puncture. Vasospasm can occur due to blood breakdown or rebleed 3\u201310 days after hemorrhage \u008e\u00a0ischemic infarct; nimodipine used to prevent\/reduce vasospasm. \u008f\u00a0risk of developing communicating and\/or obstructive hydrocephalus. Intraparenchymal Most commonly caused by systemic hemorrhage hypertension. Also seen with amyloid angiopathy (recurrent lobar hemorrhagic stroke in older adults), arteriovenous malformations, vasculitis, neoplasm. May be 2\u00ba to reperfusion injury in ischemic stroke. Hypertensive hemorrhages (Charcot- Bouchard microaneurysm) most often occur in putamen\/globus pallidus of basal ganglia (lenticulostriate vessels G ), followed by internal capsule, thalamus, pons, and cerebellum\u00a0 H .","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology SEC TION III 531 Central poststroke Neuropathic pain due to thalamic lesions. Initial paresthesias followed in weeks to months by pain allodynia (ordinarily painless stimuli cause pain) and dysesthesia (altered sensation) on the contralateral side. Occurs in 10% of stroke patients. Phantom limb pain Sensation of pain in a limb that is no longer present. Common after amputation. Associated with reorganization of 1\u00b0 somatosensory cortex. Characterized by burning, aching, or electric shock\u2013 like pain. Diffuse a onal injury Traumatic shearing of white matter tracts during rapid acceleration and\/or deceleration of the brain A (eg, motor vehicle accident). Usually results in devastating neurologic injury, often causing coma or persistent vegetative state. MRI shows multiple lesions (punctate hemorrhages) involving white matter tracts A . Aphasia Aphasia\u2014higher-order language deficit (inability to understand\/produce\/use language appropriately); caused by pathology in dominant cerebral hemisphere (usually left). TYPE Dysarthria\u2014motor inability to produce speech (movement deficit). Broca (expressive) COMMENTS Wernicke (receptive) Broca area in inferior frontal gyrus of frontal lobe. Associated with defective language production. Conduction Patients appear frustrated, insight intact. Global Broca = broken boca (boca = mouth in Spanish). Wernicke area in superior temporal gyrus of temporal lobe. Associated with impaired language comprehension. Patients do not have insight. Wernicke is a word salad and makes no sense. Can be caused by damage to arcuate fasciculus. Broca and Wernicke areas affected. uploaded by medbooksvn","532 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology Aneurysms Abnormal dilation of an artery due to weakening of vessel wall. Saccular aneurysm A Also called berry aneurysm A . Occurs at bifurcations in the circle of Willis. Most common site is junction of ACom and ACA. Associated with ADPKD, Ehlers-Danlos syndrome. Other risk Charcot-Bouchard factors: advanced age, hypertension, tobacco smoking. microaneurysm Usually clinically silent until rupture (most common complication) \u008e\u00a0subarachnoid hemorrhage (\u201cworst headache of my life\u201d or \u201cthunderclap headache\u201d) \u008e\u00a0focal neurologic deficits. Can also cause symptoms via direct compression of surrounding structures by growing aneurysm. \u0083\t ACom\u2014compression \u008e\u00a0bitemporal hemianopia (compression of optic chiasm); visual acuity deficits; rupture \u008e\u00a0ischemia in ACA distribution \u008e\u00a0contralateral lower extremity hemiparesis, sensory deficits. \u0083\t MCA\u2014rupture \u008e\u00a0ischemia in MCA distribution \u008e\u00a0contralateral upper extremity and lower facial hemiparesis, sensory deficits. \u0083\t PCom\u2014compression \u008e\u00a0ipsilateral CN III palsy \u008e\u00a0mydriasis (\u201cblown pupil\u201d); may also see ptosis, \u201cdown and out\u201d eye. Common, associated with chronic hypertension; affects small vessels (eg, lenticulostriate arteries in basal ganglia, thalamus) and can cause hemorrhagic intraparenchymal strokes. Not visible on angiography. Fever vs heat stroke Fever Heat stroke Cytokine activation during inflammation (eg, Inability of body to dissipate heat (eg, exertion) PATHOPHYSIOLOGY TEMPERATURE infection) Usually > 40\u00b0C (104\u00b0F) COMPLICATIONS Usually < 40\u00b0C (104\u00b0F) CNS dysfunction (eg, confusion), rhabdomyolysis, MANAGEMENT Febrile seizure (benign, usually self-limiting) acute kidney injury, ARDS, DIC Acetaminophen or ibuprofen for comfort (does Rapid external cooling, rehydration and not prevent future febrile seizures), antibiotic therapy if indicated electrolyte correction","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology SEC TION III 533 Seizures Characterized by synchronized, high-frequency neuronal firing. Variety of forms. Focal seizures Affect single area of the brain. Most commonly Epilepsy\u2014disorder of recurrent, unprovoked Generalized seizures originate in medial temporal lobe. Types: seizures (febrile seizures are not epilepsy). \u0083\t Focal aware (formerly called simple partial)\u2014consciousness intact; motor, Status epilepticus\u2014continuous (\u2265 5 min) or sensory, autonomic, psychic recurring seizures without interictal return to \u0083\t Focal impaired awareness (formerly called baseline consciousness that may result in brain complex partial)\u2014impaired consciousness, injury. automatisms Causes of seizures by age: Diffuse. Types: \u0083\t Children < 18\u2014genetic, infection (febrile), \u0083\t Absence (petit mal)\u20143 Hz spike-and-wave trauma, congenital, metabolic discharges, short (usually 10 seconds) \u0083\t Adults 18\u201365\u2014tumor, trauma, stroke, and frequent episodes of blank stare, no infection postictal confusion. Can be triggered by \u0083\t Adults > 65\u2014stroke, tumor, trauma, hyperventilation metabolic, infection \u0083\t Myoclonic\u2014quick, repetitive jerks; no loss of consciousness \u0083\t Tonic-clonic (grand mal)\u2014alternating stiffening and movement, postictal confusion, urinary incontinence, tongue biting \u0083\t Tonic\u2014stiffening \u0083\t Atonic\u2014\u201cdrop\u201d seizures (falls to floor); commonly mistaken for fainting Seizure Focal seizures 2\u00b0 generalized Generalized seizures Impaired consciousness? Focal aware Focal impaired Tonic-clonic Tonic Myoclonic Atonic Absence awareness (grand mal) Sti ening (petit mal) Quick Drop seizure Alternating and repetitive (falls to \ufb02oor) Blank stare sti ening and no postictal movement jerks confusion Tonic phase Drop Clonic phase uploaded by medbooksvn","534 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology Headaches Pain due to irritation of intra- or extracranial structures (eg, meninges, blood vessels). Primary headaches include tension-type, migraine, and cluster. Secondary headaches include medication CLASSIFICATION overuse, meningitis, subarachnoid hemorrhage, hydrocephalus, neoplasia, giant cell arteritis. Tension-type LOCALIZATION DURATION DESCRIPTION TREATMENT Migraine Bilateral > 30 min Steady, \u201cbandlike\u201d pain. No Acute: analgesics, NSAIDs, (typically 4\u20136 nausea or vomiting. No more acetaminophen. Cluster hr); constant than one of photophobia or phonophobia. No aura. Most Prophylaxis: TCAs (eg, common primary headache; amitriptyline), behavioral more common in females. therapy. Unilateral 4\u201372 hr Pulsating pain with nausea, Acute: NSAIDs, triptans, Unilateral photophobia, and\/or dihydroergotamine, 15 min\u20133 hr; phonophobia. May have antiemetics (eg, repetitive \u201caura.\u201d Due to irritation of prochlorperazine, CN V, meninges, or blood metoclopramide). vessels (release of vasoactive neuropeptides [eg, substance Prophylaxis: lifestyle changes P, calcitonin gene-related (eg, sleep, exercise, diet), peptide]). More common in \u03b2-blockers, amitriptyline, females. topiramate, valproate, botulinum toxin, anti-CGRP POUND\u2013Pulsatile, One-day monoclonal antibodies. duration, Unilateral, Nausea, Disabling. Acute: sumatriptan, 100% O2. Prophylaxis: verapamil. Excruciating periorbital pain (\u201csuicide headache\u201d) with autonomic symptoms (eg, lacrimation, rhinorrhea, conjunctival injection). May present with Horner syndrome. More common in males. Trigeminal neuralgia Recurrent brief episodes of intense unilateral pain in CN V distribution (usually V2 and\/or V3). Most cases are due to compression of CN V root by an aberrant vascular loop. Pain is described as electric shock\u2013like or stabbing and usually lasts seconds. Typically triggered by light facial touch or facial movements (eg, chewing, talking). Treatment: carbamazepine, oxcarbazepine.","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology SEC TION III 535 Dyskinesias PRESENTATION NOTES DISORDER Restlessness and intense urge to move Can be seen with neuroleptic use or as an adverse effect of Parkinson disease treatment Akathisia \u201cFlapping\u201d motion upon extension of wrists Asterixis Associated with hepatic encephalopathy, Wilson Athetosis Slow, snakelike, writhing movements; especially disease, and other metabolic derangements Chorea seen in the fingers Caused by lesion to basal ganglia Dystonia Sudden, jerky, purposeless movements Seen in Huntington disease Essential tremor Sustained, involuntary muscle contractions Chorea (Greek) = dancing Intention tremor Caused by lesion to basal ganglia Resting tremor High-frequency tremor with sustained posture Seen in Huntington disease and acute (eg, outstretched arms); worsened with Hemiballismus movement or anxiety rheumatic fever (Sydenham chorea). Myoclonus Slow, zigzag motion when pointing\/extending Writers cramp, blepharospasm, torticollis toward a target Treatment: botulinum toxin injection Uncontrolled movement of distal appendages Often familial (most noticeable in hands); tremor alleviated Patients often self-medicate with alcohol, which by intentional movement \u0090\u00a0tremor amplitude Sudden, wild flailing of one side of the body Treatment: nonselective \u03b2-blockers (eg, Sudden, brief, uncontrolled muscle contraction propranolol), barbiturates (primidone) Caused by cerebellar dysfunction Caused by lesion to substantia nigra Occurs at rest; \u201cpill-rolling tremor\u201d of Parkinson disease; when you park your car, it is at rest Caused by lesion to contralateral subthalamic nucleus (eg, due to lacunar stroke) In hemiballismus, half-of-body is going ballistic Jerks; hiccups; common in metabolic abnormalities (eg, renal and liver failure), Creutzfeldt-Jakob disease Restless legs syndrome Uncomfortable sensations in legs causing irresistible urge to move them. Emerge during periods of inactivity; most prominent in the evening or at night. Transiently relieved by movement (eg, walking). Usually idiopathic (often with genetic predisposition), but may be associated with iron deficiency, CKD, diabetes mellitus (especially with neuropathy). Treatment: gabapentinoids, dopamine agonists. uploaded by medbooksvn","536 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology Neurodegenerative movement disorders Parkinson disease Loss of dopaminergic neurons in substantia Affected neurons contain Lewy bodies: nigra pars compacta (depigmentation in A ). intracellular eosinophilic inclusions composed of \u03b1-synuclein B . Think \u201cParkinsynuclein.\u201d Symptoms typically manifest after age 60 (\u201cbody TRAP\u201d): AB \u0083\t Tremor (pill-rolling tremor at rest) \u0083\t Rigidity (cogwheel or leadpipe) Normal PD \u0083\t Akinesia\/bradykinesia \u008e\u00a0shuffling gait, small handwriting (micrographia) \u0083\t Postural instability (tendency to fall) Dementia is usually a late finding. Huntington disease Loss of GABAergic neurons in striatum. Atrophy of caudate and putamen with ex vacuo Autosomal dominant trinucleotide (CAG)n ventriculomegaly. repeat expansion in huntingtin (HTT) gene on chromosome 4 (4 letters) \u008e\u00a0toxic gain of \u008f\u00a0dopamine, \u0090\u00a0GABA, \u0090\u00a0ACh in brain. function. Neuronal death via NMDA receptor binding and glutamate excitotoxicity. Symptoms typically manifest between age\u00a030 and 50: chorea, athetosis, aggression, Anticipation results from expansion of CAG depression, dementia (sometimes initially repeats. Caudate loses ACh and GABA. mistaken for substance use). Dementia Decline in cognitive ability (eg, memory, executive function) with intact consciousness. Reversible Neurodegenerative causes of dementia include depression (pseudodementia), hypothyroidism, vitamin B12 deficiency, Alzheimer disease neurosyphilis, normal pressure hydrocephalus. Frontotemporal Most common cause of dementia in older Widespread cortical atrophy, especially dementia adults. Advanced age is the strongest risk hippocampus. Narrowing of gyri and widening Lewy body dementia factor. Down syndrome patients have \u008f\u00a0risk of of sulci. developing early-onset Alzheimer disease, as amyloid precursor protein (APP) is located on Senile plaques A in gray matter: extracellular chromosome 21. \u0090\u00a0ACh in brain. \u03b2-amyloid core; may cause amyloid angiopathy \u008e\u00a0intraparenchymal hemorrhage; A\u03b2 Associated with the following altered proteins: (amyloid-\u03b2) is derived from cleavage of APP. \u0083\t ApoE-2: \u0090\u00a0risk of sporadic form \u0083\t ApoE-4: \u008f\u00a0risk of sporadic form Neurofibrillary tangles B : intracellular, \u0083\t APP, presenilin-1, presenilin-2: familial hyperphosphorylated tau protein = insoluble forms (10%) with earlier onset cytoskeletal elements; number of tangles correlates with degree of dementia. ApoE-2 is \u201cprotwoctive,\u201d ApoE-4 is \u201cfour\u201d Alzheimer disease. Hirano bodies: intracellular eosinophilic proteinaceous rods in hippocampus. Formerly called Pick disease. Early changes in personality and behavior (behavioral variant), Frontal and\/or temporal lobe atrophy. or aphasia (primary progressive aphasia). Inclusions of hyperphosphorylated tau (round May have associated movement disorders. Pick bodies C ) or ubiquitinated TDP-43. Visual hallucinations (\u201chaLewycinations\u201d), Intracellular Lewy bodies primarily in cortex. dementia with fluctuating cognition\/ Called Lewy body dementia if cognitive and alertness, REM sleep behavior disorder, and parkinsonism. motor symptom onset < 1 year apart, otherwise considered dementia 2\u00b0 to Parkinson disease.","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology SEC TION III 537 Dementia (continued) 2nd most common cause of dementia in older MRI or CT shows multiple cortical and\/or Vascular adults. Result of multiple arterial infarcts and\/ subcortical infarcts D . Vascular dementia or chronic ischemia. Infective Step-wise decline in cognitive ability with late- Creutzfeldt-Jakob onset memory impairment. disease Rapidly progressive (weeks to months) dementia Spongiform cortex E (vacuolation without HIV-associated with myoclonus (\u201cstartle myoclonus\u201d) and inflammation). dementia ataxia. Fatal. Caused by prions: PrPc \u008e\u00a0PrPsc (\u03b2-pleated sheet resistant to proteases). Associated with periodic sharp waves on EEG A and \u008f\u00a014-3-3 protein in CSF. Typically sporadic, but may be transmitted by contaminated materials (eg, corneal transplant, neurosurgical equipment). Subcortical dysfunction associated with Diffuse gray matter and subcortical atrophy. advanced HIV infection. Characterized by Microglial nodules with multinucleated giant cognitive deficits, gait disturbance, irritability, depressed mood. cells. B CD E uploaded by medbooksvn","538 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology Idiopathic intracranial Also called pseudotumor cerebri. \u008f\u00a0ICP with no obvious findings on imaging. Risk factors include hypertension female sex, Tetracyclines, Obesity, vitamin A excess, Danazol (female TOAD). Associated with dural venous sinus stenosis. Findings: headache, tinnitus, diplopia (usually from CN VI palsy), no change in mental status. Impaired optic nerve axoplasmic flow \u008e\u00a0papilledema. Visual field testing shows enlarged blind spot and peripheral constriction. Lumbar puncture reveals \u008f\u00a0opening pressure and provides temporary headache relief. Treatment: weight loss, acetazolamide, invasive procedures for refractory cases (eg,\u00a0CSF shunt placement, optic nerve sheath fenestration surgery for visual loss). Hydrocephalus \u008f\u00a0CSF volume \u008e\u00a0ventricular dilation +\/\u2212 \u008f\u00a0ICP. Communicating Communicating \u0090 CSF absorption by arachnoid granulations (eg, arachnoid scarring post-meningitis) \u008e\u00a0\u008f\u00a0ICP, hydrocephalus papilledema, herniation. Normal pressure Affects older adults; idiopathic; CSF pressure elevated only episodically; does not result in hydrocephalus increased subarachnoid space volume. Expansion of ventricles A distorts the fibers of the corona radiata \u008e\u00a0triad of gait apraxia (magnetic gait), cognitive dysfunction, and urinary incontinence. \u201cWobbly, wacky, and wet.\u201d Symptoms potentially reversible with CSF drainage via lumbar puncture or shunt placement. Noncommunicating (obstructive) Noncommunicating Caused by structural blockage of CSF circulation within ventricular system (eg, stenosis of hydrocephalus aqueduct of Sylvius, colloid cyst blocking foramen of Monro, tumor B ). Hydrocephalus mimics Ex vacuo Appearance of \u008f CSF on imaging C , but is actually due to \u0090\u00a0brain tissue and neuronal atrophy ventriculomegaly (eg,\u00a0Alzheimer disease, advanced HIV, frontotemporal dementia, Huntington disease). ICP is normal; NPH triad is not seen. ABC","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology SEC TION III 539 Multiple sclerosis Autoimmune inflammation and demyelination of CNS (brain and spinal cord) with subsequent axonal damage. Most often affects females aged 20\u201340; more common in individuals who grew FINDINGS up farther from equator and with low serum vitamin D levels. Can present with TREATMENT \u0083\t Optic neuritis (acute painful monocular visual loss, associated with relative afferent pupillary A defect) \u0083\t Brainstem\/cerebellar syndromes (eg, diplopia, ataxia, scanning speech, intention tremor, nystagmus\/INO [bilateral > unilateral]) \u0083\t Pyramidal tract demyelination (eg, weakness, spasticity) \u0083\t Spinal cord syndromes (eg, electric shock\u2013like sensation along cervical spine on neck flexion, neurogenic bladder, paraparesis, sensory manifestations affecting the trunk or one or more extremities) Symptoms may exacerbate with increased body temperature (eg, hot bath, exercise). Relapsing and remitting is most common clinical course. \u008f IgG level and myelin basic protein in CSF. Oligoclonal bands aid in diagnosis. MRI is gold standard. Periventricular plaques A (areas of oligodendrocyte loss and reactive gliosis). Multiple white matter lesions disseminated in space and time. Stop relapses and halt\/slow progression with disease-modifying therapies (eg, \u03b2-interferon, glatiramer, natalizumab). Treat acute flares with IV steroids. Symptomatic treatment for neurogenic bladder (catheterization, muscarinic antagonists, botulinum toxin injection), spasticity (baclofen, GABAB receptor agonists), pain (TCAs, anticonvulsants). Neurologic Ophthalmic Fatigue Optic neuritis Diplopia Depression Nystagmus Ataxia INO Intention tremor Speech Spinal cord Dysarthria Sensory symptoms Scanning speech Weakness Spasticity Urinary Incontinence uploaded by medbooksvn","540 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology Other demyelinating and dysmyelinating disorders Osmotic demyelination Also called central pontine myelinolysis. Massive axonal demyelination in pontine white matter syndrome A 2\u00b0 to rapid osmotic changes, most commonly iatrogenic correction of hyponatremia but also rapid shifts of other osmolytes (eg, glucose). Acute paralysis, dysarthria, dysphagia, diplopia, loss of A consciousness. Can cause \u201clocked-in syndrome.\u201d Correcting serum Na+ too fast: \u0083\t \u201cFrom low to high, your pons will die\u201d (osmotic demyelination syndrome) \u0083\t \u201cFrom high to low, your brains will blow\u201d (cerebral edema\/herniation) Acute inflammatory Most common subtype of Guillain-Barre\u0301 syndrome. demyelinating Autoimmune condition that destroys Schwann cells via inflammation and demyelination of motor polyneuropathy fibers, sensory fibers, peripheral nerves (including CN III-XII). Likely facilitated by molecular Acute disseminated mimicry and triggered by inoculations or stress. Despite association with infections (eg, (postinfectious) Campylobacter jejuni, viruses [eg, Zika]), no definitive causal link to any pathogen. encephalomyelitis Results in symmetric ascending muscle weakness\/paralysis and depressed\/absent DTRs beginning Charcot-Marie-Tooth in lower extremities. Facial paralysis (usually bilateral) and respiratory failure are common. May disease see autonomic dysregulation (eg, cardiac irregularities, hypertension, hypotension) or sensory abnormalities. Most patients survive with good functional recovery. Progressive multifocal \u008f\u00a0CSF protein with normal cell count (albuminocytologic dissociation). leukoencephalopathy Respiratory support is critical until recovery. Disease-modifying treatment: plasma exchange or B IV\u00a0immunoglobulins. No role for steroids. Multifocal inflammation and demyelination after infection or vaccination. Presents with rapidly progressive multifocal neurologic symptoms, altered mental status. Also called hereditary motor and sensory neuropathy. Group of progressive hereditary nerve disorders related to the defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath. Typically autosomal dominant and associated with foot deformities (eg, pes cavus, hammer toe), lower extremity weakness (eg, foot drop), and sensory deficits (Can\u2019t Move Toes). Most common type, CMT1A, is caused by PMP22 gene duplication. Demyelination of CNS B due to destruction of oligodendrocytes (2\u00b0 to reactivation of latent JC virus infection). Associated with severe immunosuppression (eg, lymphomas and leukemias, AIDS, organ transplantation). Rapidly progressive, usually fatal. Predominantly involves parietal and occipital areas; visual symptoms are common. \u008f\u00a0risk associated with natalizumab. Other disorders Krabbe disease, metachromatic leukodystrophy, adrenoleukodystrophy.","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology SEC TION III 541 Neurocutaneous disorders DISORDER GENETICS PRESENTATION NOTES Sturge-Weber Congenital Capillary vascular malformation \u008e\u00a0port- Also called encephalotrigeminal syndrome nonhereditary wine stain A (nevus flammeus or non- angiomatosis. anomaly of neural neoplastic birthmark) in CN V1\/V2 crest derivatives. distribution; ipsilateral leptomeningeal Somatic mosaicism of angioma with calcifications B \u008e seizures\/ an activating mutation epilepsy; intellectual disability; episcleral in one copy of the hemangioma \u008e\u00a0\u008f\u00a0IOP \u008e\u00a0early-onset GNAQ gene. glaucoma. Tuberous sclerosis AD, variable expression. Hamartomas in CNS and skin, angiofibromas \u008f\u00a0incidence of subependymal Mutation in tumor C , mitral regurgitation, ash-leaf spots giant cell astrocytomas and suppressor genes TSC1 D , cardiac rhabdomyoma, intellectual ungual fibromas. on chromosome 9 disability, renal angiomyolipoma E , (hamartin), TSC2 seizures, shagreen patches. on chromosome 16 (tuberin; pronounce \u201ctwoberin\u201d). Neurofibromatosis AD, 100% penetrance. Caf\u00e9-au-lait spots F , Intellectual disability, Also called von Recklinghausen type I disease. Mutation in NF1 tumor Cutaneous neurofibromas\u00a0 G , Lisch 17 letters in \u201cvon suppressor gene on nodules (pigmented iris hamartomas H ), Recklinghausen.\u201d chromosome 17 Optic gliomas, Pheochromocytomas, CICLOPSS. (encodes neurofibromin, Seizures\/focal neurologic Signs (often a negative RAS from meningioma), bone lesions (eg, regulator). sphenoid dysplasia). Neurofibromatosis AD. Mutation in NF2 Bilateral vestibular schwannomas, juvenile NF2 affects 2 ears, 2 eyes. type II tumor suppressor cataracts, meningiomas, ependymomas. gene (merlin) on chromosome 22. von Hippel-Lindau AD. Deletion of VHL Hemangioblastomas (high vascularity with Numerous tumors, benign and disease gene on chromosome hyperchromatic nuclei I ) in retina, malignant. HARP. 3p. pVHL brainstem, cerebellum, spine J ; ubiquitinates hypoxia- Angiomatosis; bilateral Renal cell VHL = 3 letters = chromosome inducible factor 1a. carcinomas; Pheochromocytomas. 3; associated with RCC (also 3 letters). A B CDE F GH I J uploaded by medbooksvn","542 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology Adult primary brain tumors TUMOR DESCRIPTION HISTOLOGY Glioblastoma Grade IV astrocytoma. Common, highly Astrocyte origin, GFAP \u2295. \u201cPseudopalisading\u201d malignant 1\u00b0 brain tumor with ~ 1-year pleomorphic tumor cells B border central areas median survival. Found in cerebral of necrosis, hemorrhage, and\/or microvascular hemispheres. Can cross corpus callosum proliferation. (\u201cbutterfly glioma\u201d A ). Associated with EGFR amplification. Oligodendroglioma Relatively rare, slow growing. Most often in Oligodendrocyte origin. \u201cFried egg\u201d cells\u2014round frontal lobes C . nuclei with clear cytoplasm D . Often calcified. \u201cChicken-wire\u201d capillary pattern. Meningioma Common, typically benign. Females > males. Arachnoid cell origin. Spindle cells Occurs along surface of brain or spinal cord. concentrically arranged in a whorled pattern; Extra-axial (external to brain parenchyma) psammoma bodies (laminated calcifications, and may have a dural attachment (\u201ctail\u201d E ). arrow in F ). Often asymptomatic; may present with seizures or focal neurologic signs. Resection and\/or radiosurgery. Hemangioblastoma Most often cerebellar G . Associated with von Blood vessel origin. Closely arranged, thin- Hippel-Lindau syndrome when found with walled capillaries with minimal intervening retinal angiomas. Can produce erythropoietin parenchyma H . \u008e\u00a02\u00b0 polycythemia. Pituitary adenoma May be nonfunctioning (silent) or Hyperplasia of only one type of endocrine cells hyperfunctioning (hormone-producing). found in pituitary. Most commonly from Nonfunctional tumors present with mass effect lactotrophs (prolactin) J \u008e\u00a0hyperprolactinemia. (eg, bitemporal hemianopia [due to pressure Less commonly, from somatotrophs (GH) on optic chiasm I ]). Pituitary apoplexy \u008e\u00a0acromegaly, gigantism; corticotrophs (ACTH) \u008e\u00a0hypopituitarism. \u008e\u00a0Cushing disease. Rarely, from thyrotrophs (TSH), gonadotrophs (FSH, LH). Prolactinoma classically presents as galactorrhea, amenorrhea, \u0090\u00a0bone density due to suppression of estrogen in females and as \u0090\u00a0libido, infertility in males. Treatment: dopamine agonists (eg, bromocriptine, cabergoline), transsphenoidal resection. Schwannoma Classically at the cerebellopontine angle K , Schwann cell origin, S-100 \u2295. Biphasic, dense, benign, involving CNs V, VII, and VIII, but hypercellular areas containing spindle cells can be along any peripheral nerve. Often alternating with hypocellular, myxoid areas L . localized to CN VIII in internal acoustic meatus \u008e\u00a0vestibular schwannoma (can present as hearing loss and tinnitus). Bilateral vestibular schwannomas found in NF-2. Resection or stereotactic radiosurgery.","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology SEC TION III 543 Adult primary brain tumors (continued) A BCD E F GH I Normal J K L Patient uploaded by medbooksvn","544 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology Childhood primary brain tumors TUMOR DESCRIPTION HISTOLOGY Pilocytic astrocytoma Low-grade astrocytoma. Most common 1\u00b0 Astrocyte origin, GFAP \u2295. Bipolar neoplastic brain tumor in childhood. Usually well cells with hairlike projections. Associated with circumscribed. In children, most often found microcysts and Rosenthal fibers (eosinophilic, in posterior fossa A (eg, cerebellum). May be corkscrew fibers B ). Cystic + solid (gross). supratentorial. Benign; good prognosis. Form of primitive neuroectodermal tumor Medulloblastoma Most common malignant brain tumor in (PNET). Homer-Wright rosettes (small blue childhood. Commonly involves cerebellum cells surrounding central area of neuropil D ). C . Can compress 4th ventricle, causing noncommunicating hydrocephalus Synaptophysin \u2295. \u008e\u00a0headaches, papilledema. Can involve the cerebellar vermis \u008e\u00a0truncal ataxia. Can send Ependymal cell origin. Characteristic \u201cdrop metastases\u201d to spinal cord. perivascular pseudorosettes F . Rod-shaped blepharoplasts (basal ciliary bodies) found near Ependymoma Most commonly found in 4th ventricle E . Can the nucleus. cause hydrocephalus. Poor prognosis. Derived from remnants of Rathke pouch Craniopharyngioma Most common childhood supratentorial (ectoderm) H . Cholesterol crystals found in Pineal gland tumors tumor. Calcification is common G . May be \u201cmotor oil\u201d-like fluid within tumor. confused with pituitary adenoma (both cause bitemporal hemianopia). Associated with a Similar to testicular seminomas. high recurrence rate. CD Most commonly extragonadal germ cell tumors. \u008f incidence in males. Present with obstructive hydrocephalus (compression of cerebral aqueduct), Parinaud syndrome (compression of dorsal midbrain)\u2014triad of upward gaze palsy, convergence-retraction nystagmus, and light-near dissociation. AB E F GH","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology SEC TION III 545 Herniation syndromes C\u0007 ingulate (subfalcine) herniation under Can compress anterior cerebral artery. falx cerebri Falx cerebri Central\/downward transtentorial Caudal displacement of brainstem \u008e\u00a0rupture of herniation paramedian basilar artery branches \u008e\u00a0Duret Duret Lateral \u0007Uncal transtentorial herniation hemorrhages. Usually fatal. hemorrhage ventricles \u0007Cerebellar tonsillar herniation into the Uncus = medial temporal lobe. Early herniation Supratentorial foramen magnum \u008e\u00a0ipsilateral blown pupil (unilateral CN III mass compression), contralateral hemiparesis. Late Uncus herniation \u008e\u00a0coma, Kernohan phenomenon Tentorium (misleading contralateral blown pupil and cerebelli ipsilateral hemiparesis due to contralateral Kernohan compression against Kernohan notch). notch Coma and death result when these herniations compress the brainstem. Motor neuron signs UMN LESION LMN LESION COMMENTS SIGN + + Lower motor neuron (LMN) = everything \u2212 + lowered (less muscle mass, \u0090 muscle tone, \u0090 Weakness \u2212 + reflexes, downgoing toes) Atrophy \u008f \u0090 Fasciculations \u008f \u0090 Upper motor neuron (UMN) = everything up Reflexes + \u2212 (tone, DTRs, toes) Tone + \u2212 Babinski \u2212 + Fasciculations = muscle twitching Spastic paresis + \u2212 Positive Babinski is normal in infants Flaccid paralysis Clasp knife spasticity uploaded by medbooksvn","546 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology Spinal cord lesions Destruction of anterior horns by poliovirus. Fecal-oral transmission \u008e\u00a0replication in lymphoid Poliomyelitis tissue of oropharynx and small intestine \u008e\u00a0spread to CNS via bloodstream. Spinal muscular Acute LMN signs (asymmetric weakness) and symptoms of viral meningitis (eg, fever, headache, atrophy neck stiffness). Respiratory muscle involvement leads to respiratory failure. Posterior spinal arteries CSF shows \u008f\u00a0WBCs (lymphocytic pleocytosis) and slight \u008f\u00a0of protein (with no change in CSF glucose). Poliovirus can be isolated from stool or throat secretions. Congenital degeneration of anterior horns. Autosomal recessive SMN1 mutation (encodes survival motor neuron protein) \u008e\u00a0defective snRNP assembly \u008e\u00a0LMN apoptosis. Spinal muscular atrophy type 1 (most common) is also called Werdnig-Hoffmann disease. LMN signs only (symmetric weakness). \u201cFloppy baby\u201d with marked hypotonia (flaccid paralysis) and tongue fasciculations. Amyotrophic lateral Combined UMN (corticospinal\/corticobulbar) and LMN (brainstem\/spinal cord) degeneration. scleAnPrtooesrtieosrriiosspr isnpailnaarltaerrtyeries Usually idiopathic. Familial form (less common) may be linked to SOD1 mutations (encodes superoxide dismutase 1). ALS is also called Lou Gehrig disease. Posterior spinal arteries LMN signs: flaccid limb weakness, fasciculations, atrophy, bulbar palsy (dysarthria, dysphagia, TabesAndteroiorrsspianall iasrtery tongue atrophy). UMN signs: spastic limb weakness, hyperreflexia, clonus, pseudobulbar palsy (dysarthria, dysphagia, emotional lability). No sensory or bowel\/bladder deficits. Posterior spinal arteries Anterior spinal artery Fatal (most often from respiratory failure). Treatment: riluzole (\u201criLouzole\u201d). Degeneration\/demyelination of dorsal columns and roots by T pallidum (3\u00b0 syphilis). Causes Posterior spinal arteries progressive sensory ataxia (impaired proprioception \u008e\u00a0poor coordination). \u2295\u00a0Romberg sign and Subacute combined absent DTRs. Associated with shooting pain, Argyll Robertson pupils, Charcot joints. degeneration Demyelination of Spinocerebellar tracts, lateral Corticospinal tracts, and Dorsal columns (SCD) Anterior spinal artery due to vitamin B12 deficiency. Ataxic gait, paresthesias, impaired position\/vibration sense (\u2295\u00a0Romberg sign), UMN signs. Anterior spinal artery Anterior spinal artery Spinal cord infarction sparing dorsal columns and Lissauer tract. Watershed area is mid-thoracic occlusion ASA territory, as the artery of Adamkiewicz supplies ASA below T8. Can be caused by aortic aneurysm repair. Posterior spinal arteries Presents with UMN signs below the lesion (corticospinal tract), LMN signs at the level of the lesion (anterior horn), and loss of pain and temperature sensation below the lesion (spinothalamic tract). Anterior spinal artery","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology SEC TION III 547 Brown-S\u00e9quard Hemisection of spinal cord. Findings: Level of lesion syndrome I\u0007psilateral loss of all sensation at level of lesion Loss of all Right Left I\u0007psilateral LMN signs (eg, flaccid paralysis) at sensation level of lesion LMN signs Lesion \u0007Ipsilateral UMN signs below level of lesion (due to corticospinal tract damage) UMN signs \u0007Ipsilateral loss of proprioception, vibration, Impaired Impaired pain, and fine (2-point discrimination) touch below proprioception, temperature, level of lesion (due to dorsal column damage) vibration, \ufb01ne crude touch C\u0007 ontralateral loss of pain, temperature, and touch crude (non-discriminative) touch below level of lesion (due to spinothalamic tract damage) If lesion occurs above T1, patient may present with ipsilateral Horner syndrome due to damage of oculosympathetic pathway. Friedreich ataxia Autosomal recessive trinucleotide repeat Hypertrophic cardiomyopathy A disorder (GAA)n on chromosome 9 in gene that Diabetes mellitus encodes frataxin (iron-binding protein). Leads Kyphoscoliosis Cerebral palsy to impairment in mitochondrial functioning. Degeneration of lateral corticospinal tract High arches (spastic paralysis), spinocerebellar tract (pes cavus) (ataxia), dorsal columns (\u0090\u00a0vibratory sense, proprioception), and dorsal root ganglia Hammer toe (loss of DTRs). Staggering gait, frequent falling, nystagmus, dysarthria, pes cavus, hammer toes, diabetes mellitus, hypertrophic cardiomyopathy (cause of death). Presents in childhood with kyphoscoliosis A . Friedreich is fratastic (frataxin): he\u2019s your favorite frat brother, always staggering and falling but has a sweet, big heart. Ataxic GAAit. Permanent motor dysfunction resulting from nonprogressive injury to developing fetal\/infant brain. Most common movement disorder in children. Multifactorial etiology; prematurity and low birth weight are the strongest risk factors. Associated with development of periventricular leukomalacia (focal necrosis of white matter tracts). Presents with UMN signs (eg, spasticity, hyperreflexia) affecting \u2265 1 limbs, persistence of primitive reflexes, abnormal posture, developmental delay in motor skills, neurobehavioral abnormalities (excessive docility, irritability). Treatment: muscle relaxants (eg, baclofen), botulinum toxin injections, selective dorsal rhizotomy. Prevention: prenatal magnesium sulfate for high-risk pregnancies \u0090\u00a0incidence and severity. uploaded by medbooksvn","548 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology Common cranial nerve lesions CN V motor lesion Jaw deviates toward side of lesion due to unopposed force from the opposite pterygoid muscle. CN X lesion Uvula deviates away from side of lesion. Weak side collapses and uvula points away. CN XI lesion Weakness turning head to contralateral side of lesion (SCM). Shoulder droop on side of lesion (trapezius). CN XII lesion LMN lesion. Tongue deviates toward side of lesion (\u201click your wounds\u201d) due to weakened tongue muscles on affected side. Facial nerve lesions Bell palsy is the most common cause of peripheral facial palsy A . Usually develops after HSV A reactivation. Treatment: glucocorticoids +\/\u2013 acyclovir. Most patients gradually recover function, but aberrant regeneration can occur. Other causes of peripheral facial palsy include Lyme disease, herpes zoster (Ramsay Hunt syndrome), sarcoidosis, tumors (eg, parotid gland), diabetes mellitus. LESION LOCATION Upper motor neuron lesion Lower motor neuron lesion Facial nucleus, anywhere along CN VII AFFECTED SIDE Motor cortex, connection from motor cortex to MUSCLES INVOLVED facial nucleus in pons Ipsilateral FOREHEAD INVOLVEMENT Upper and lower muscles of facial expression OTHER SYMPTOMS Contralateral Affected Lower muscles of facial expression Incomplete eye closure (dry eyes, corneal Spared, due to bilateral UMN innervation Variable; depends on size of lesion ulceration), hyperacusis, loss of taste sensation to anterior tongue Face area Face area Face area Face area of motor of motor of motor of motor cortex cortex cortex cortex Corticobulbar tract Upper Upper (UMN lesion\u2013central) division division Lower Facial Lower Facial division nucleus division nucleus CN VII (LMN lesion\u2013peripheral)","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Otology SEC TION III 549 ` \u2009NEUROLOGY \u2014 OTOLOGY Tympanic membrane Auditory anatomy and physiology External auditory Semicircular canal canals Auricle Vestibule (pinna) Cochlea Oval window Ossicles Pharyngotympanic (eustachian) tube External Middle Internal (outer) ear ear (inner) ear Outer ear Visible portion of ear (pinna), includes auditory canal and tympanic membrane. Transfers sound Middle ear waves via vibration of tympanic membrane. Inner ear Air-filled space with three bones called the ossicles (malleus, incus, stapes). Ossicles conduct and Otitis externa amplify sound from tympanic membrane to inner ear. A Snail-shaped, fluid-filled cochlea. Contains basilar membrane that vibrates 2\u00b0 to sound waves. Otitis media Vibration transduced via specialized hair cells \u008e auditory nerve signaling \u008e\u00a0brainstem. A Each frequency leads to vibration at specific location on basilar membrane (tonotopy): \u0083\t Low frequency heard at apex near helicotrema (wide and flexible). \u0083\t High frequency heard best at base of cochlea (thin and rigid). Inflammation of external auditory canal. Most commonly due to Pseudomonas. Associated with water exposure (swimmer\u2019s ear), ear canal trauma\/occlusion (eg, hearing aids). Presents with otalgia that worsens with ear manipulation, pruritus, hearing loss, discharge A . Malignant (necrotizing) otitis externa\u2014invasive infection causing osteomyelitis. Complication of otitis externa mostly seen in older patients with diabetes. Presents with severe otalgia and otorrhea. May lead to cranial nerve palsies. Physical exam shows granulation tissue in ear canal. Inflammation of middle ear. Most commonly due to nontypeable Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis. Associated with eustachian tube dysfunction, which promotes overgrowth of bacterial colonizers of upper respiratory tract. Usually seen in children < 2 years old. Presents with fever, otalgia, hearing loss. Physical exam shows bulging, erythematous tympanic membrane A that may rupture. Mastoiditis\u2014infection of mastoid process of temporal bone. Complication of acute otitis media due to continuity of middle ear cavity with mastoid air cells. Presents with postauricular pain, erythema, swelling. May lead to brain abscess. uploaded by medbooksvn","550 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Otology Common causes of hearing loss Noise-induced Damage to stereociliated cells in organ of Corti. Loss of high-frequency hearing first. Sudden hearing loss extremely loud noises can produce hearing loss due to tympanic membrane rupture. Presbycusis Aging-related progressive bilateral\/symmetric sensorineural hearing loss (often of higher frequencies) due to destruction of hair cells at the cochlear base (preserved low-frequency hearing at apex). Diagnosing hearing loss Normal Conductive Sensorineural Weber test Tuning fork on vertex of skull No localization Localizes to a ected ear Localizes to una ected ear \u2193 transmission of background noise \u2193 transmission of all sound Rinne test Tuning fork in front of ear (air conduction, AC), Tuning fork on mastoid process (bone conduction, BC) AC > BC BC > AC AC > BC Cholesteatoma Abnormal growth of keratinized squamous epithelium in middle ear A (\u201cskin in wrong place\u201d). A Usually acquired, but can be congenital. 1\u00b0 acquired results from tympanic membrane retraction pockets that form due to eustachian tube dysfunction. 2\u00b0 acquired results from tympanic membrane perforation (eg, due to otitis media) that permits migration of squamous epithelium to middle ear. Classically presents with painless otorrhea. May erode ossicles \u008e\u00a0conductive hearing loss. Vertigo Sensation of spinning while actually stationary. Subtype of \u201cdizziness,\u201d but distinct from Peripheral vertigo \u201clightheadedness.\u201d Peripheral vertigo is more common than central vertigo. Central vertigo Due to inner ear pathologies such as semicircular canal debris (benign paroxysmal positional vertigo), vestibular neuritis, M\u00e9ni\u00e8re disease\u2014endolymphatic hydrops (\u008f endolymph in inner ear) \u008e triad of vertigo, sensorineural hearing loss, tinnitus (\u201cmen wear vests\u201d). Findings: mixed horizontal-torsional nystagmus (never purely torsional or vertical) that does not change direction and is suppressible with visual fixation. Due to brainstem or cerebellar lesions (eg, stroke affecting vestibular nuclei, demyelinating disease, or posterior fossa tumor). Findings: nystagmus of any direction that is not suppressible with visual fixation, neurologic findings (eg, diplopia, ataxia, dysmetria).","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014OPHTHALMOLOGY SEC TION III 551 ` \u2009NEUROLOGY \u2014 O P HTH A LMOLOGY Vitreous chamber Sclera (outer) Optic disc Choroid (middle) Normal eye anatomy Retina A (inner) A Fovea Ciliary body (middle) Zonular \ufb01bers Optic nerve Cornea (outer) Iris (middle) Central Central retinal retinal Pupil vein artery Lens Anterior chamber Posterior chamber ANTERIOR SEGMENT POSTERIOR SEGMENT (anterior chamber + posterior chamber) Conjunctivitis Inflammation of the conjunctiva \u008e\u00a0red eye A . A Allergic\u2014itchy eyes, bilateral. Bacterial\u2014pus; treat with antibiotics. Viral\u2014most common, often adenovirus; sparse mucous discharge, swollen preauricular node, \u008f\u00a0lacrimation; self-resolving. Refractive errors Common cause of impaired vision, correctable with glasses. Hyperopia Also called \u201cfarsightedness.\u201d Eye too short for refractive power of cornea and lens \u008e light focused Myopia behind retina. Correct with convex (converging) lenses. Astigmatism Also called \u201cnearsightedness.\u201d Eye too long for refractive power of cornea and lens \u008e light focused in front of retina. Correct with concave (diverging) lens. Abnormal curvature of cornea \u008e\u00a0different refractive power at different axes. Correct with cylindrical lens. uploaded by medbooksvn","552 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014OPHTHALMOLOGY Lens disorders Aging-related impaired accommodation (focusing on near objects), primarily due to \u0090\u00a0lens Presbyopia elasticity. Patients often need reading glasses or magnifiers. Cataract Painless, often bilateral, opacification of lens A . Can result in glare and \u0090\u00a0vision, especially at A night, and loss of the red reflex. Acquired risk factors: \u008f\u00a0age, tobacco smoking, alcohol overuse, excessive sunlight, prolonged glucocorticoid use, diabetes mellitus, trauma, infection. Congenital risk factors: classic galactosemia, galactokinase deficiency, trisomies (13, 18, 21), TORCH infections (eg, rubella), Marfan syndrome, Alport syndrome, myotonic dystrophy, NF-2. Treatment: surgical removal of lens and replacement with an artificial lens. Lens dislocation Also called ectopia lentis. Displacement or malposition of lens. Usually due to trauma, but may occur in association with systemic diseases (eg, Marfan syndrome, homocystinuria). Aqueous humor pathway \u201cAngle\u201d of the eye Cornea Trabecular out\ufb02ow (90%) Anterior chamber Posterior chamber Drainage through trabecular meshwork canal of Schlemm episcleral vasculature with M3 agonist (eg, carbachol, pilocarpine) \u2193 Episcleral Trabecular meshwork \u2193 vessels \u2193 Canal of \u2193 Schlemm Uveoscleral out\ufb02ow (10%) Sclera Iris Iris Drainage into uvea and sclera SDpilhaitnocrtmerumsculesc(l\u03b1e1()M3) with prostaglandin agonists (eg, Lens latanoprost, bimatoprost) Suspended from ciliary body by zonule \ufb01bers. Muscular \ufb01bers Ciliary body Lens Vitreous chamber and position. Aqueous humor Produced by nonpigmented epithelium on ciliary body \u2193 by \u03b2-blockers (eg, timolol), \u03b12-agonists (eg, brimonidine), and carbonic anhydrase inhibitors (eg, acetazolamide)","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014OPHTHALMOLOGY SEC TION III 553 Glaucoma Optic neuropathy causing progressive vision loss (peripheral \u008e central). Usually, but not always, accompanied by \u008f intraocular pressure (IOP). Etiology is most often 1\u00b0, but can be 2\u00b0 to an Open-angle glaucoma identifiable cause (eg, uveitis, glucocorticoids). Funduscopy: optic disc cupping (normal A vs thinning of outer rim of optic disc B ). Treatment: pharmacologic or surgical lowering of IOP. Angle-closure glaucoma Anterior chamber angle is open (normal). Most common type in US. Associated with \u008f resistance to aqueous humor drainage through trabecular meshwork. Risk factors: \u008f age, race (\u008f incidence in Black population), family history, diabetes mellitus. Typically asymptomatic and discovered incidentally. Anterior chamber angle is narrowed or closed. Associated with anatomic abnormalities (eg, anteriorly displaced lens resting against central iris) \u008e \u0090 aqueous flow through pupil (pupillary block) \u008e pressure buildup in posterior chamber \u008e peripheral iris pushed against cornea \u008e obstruction of drainage pathways by the iris. Usually chronic and asymptomatic, but may develop acutely. Acute angle-closure glaucoma\u2014complete pupillary block causing abrupt angle closure and rapid \u008f IOP. Presents with severe eye pain, conjunctival erythema C , sudden vision loss, halos around lights, headache, fixed and mid-dilated pupil, nausea and vomiting. Hurts in a hurry with halos, a headache, and a \u201chalf-dilated\u201d pupil. True ophthalmic emergency that requires immediate management to prevent blindness. Mydriatic agents are contraindicated. ABC Normal Cupping Acute angle closure Open-angle glaucoma Angle-closure glaucoma Normal aqueous \ufb02ow Obstruction of drainage Abnormal aqueous \ufb02ow pathways by the iris \uf068 trabecular Closed angle out\ufb02ow resistance Open angle Pupillary block uploaded by medbooksvn","554 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014OPHTHALMOLOGY Retinal disorders Degeneration of macula (central area of retina) \u008e loss of central vision (scotomas). Two types: Age-related macular \u0083\t Dry (most common)\u2014gradual \u0090 in vision with subretinal deposits (drusen, arrow in A ). degeneration \u0083\t Wet\u2014rapid \u0090 in vision due to bleeding 2\u00b0 to choroidal neovascularization. Distortion of straight Diabetic retinopathy lines (metamorphopsia) is an early symptom. Hypertensive Chronic hyperglycemia \u008e \u008f permeability and occlusion of retinal vessels. Two types: retinopathy \u0083\t Nonproliferative (most common)\u2014microaneurysms, hemorrhages (arrows in B ), cotton-wool Retinal artery spots, hard exudates. Vision loss mainly due to macular edema. occlusion \u0083\t Proliferative\u2014retinal neovascularization due to chronic hypoxia. Abnormal new vessels may Retinal vein occlusion cause vitreous hemorrhage and tractional retinal detachment. Retinal detachment Chronic hypertension \u008e spasm, sclerosis, and fibrinoid necrosis of retinal vessels. Funduscopy: arteriovenous nicking, microaneurysms, hemorrhages, cotton-wool spots (blue arrow in C ), hard Retinitis pigmentosa exudates (may form macular \u201cstar,\u201d red arrow in C ). Presence of papilledema is indicative of hypertensive emergency and warrants immediate lowering of blood pressure. Retinopathy of prematurity Blockage of central or branch retinal artery usually due to embolism (carotid artery atherosclerosis Papilledema > cardiogenic); less commonly due to giant cell arteritis. Presents with acute, painless monocular vision loss. Funduscopy: cloudy retina with \u201ccherry-red\u201d spot at fovea D , identifiable retinal emboli (eg, cholesterol crystals appear as small, yellow, refractile deposits in arterioles). Central retinal vein occlusion is due to 1\u00b0 thrombosis; branch retinal vein occlusion is due to 2\u00b0 thrombosis at arteriovenous crossings (sclerotic arteriole compresses adjacent venule causing turbulent blood flow). Funduscopy: retinal hemorrhage and venous engorgement (\u201cblood and thunder\u201d appearance; arrows in E ), retinal edema in affected areas. Separation of neurosensory retina from underlying retinal pigment epithelium \u008e loss of choroidal blood supply \u008e hypoxia and degeneration of photoreceptors. Two types: \u0083\t Rhegmatogenous (most common)\u2014due to retinal tears; often associated with posterior vitreous detachment (\u008f risk with advanced age, high myopia), less frequently traumatic. \u0083\t Nonrhegmatogenous\u2014tractional or exudative (fluid accumulation). Commonly presents with symptoms of posterior vitreous detachment (eg, floaters, light flashes) followed by painless monocular vision loss (\u201cdark curtain\u201d). Funduscopy: opacification and wrinkling of detached retina F , change in vessel direction. Surgical emergency. Group of inherited dystrophies causing progressive degeneration of photoreceptors and retinal pigment epithelium. May be associated with abetalipoproteinemia. Early symptoms: night blindness (nyctalopia) and peripheral vision loss. Funduscopy: triad of optic disc pallor, retinal vessel attenuation, and retinal pigmentation with bone spicule-shaped deposits G . Preterm birth \u008e\u00a0loss of normal hypoxic environment in utero \u008e\u00a0relative hyperoxia (\u008f\u00a0with supplemental O2 for NRDS) \u008e\u00a0\u0090\u00a0VEGF \u008e\u00a0arrest of normal retinal vascularization. As the eyes grow \u008e\u00a0hypoxia of avascular retina \u008e\u00a0\u008f\u00a0VEGF \u008e\u00a0retinal neovascularization (may cause tractional retinal detachment). Common cause of childhood blindness. Optic disc swelling (usually bilateral) due to \u008f ICP (eg, 2\u00b0 to mass effect). Results from impaired axoplasmic flow in optic nerve. Funduscopy: elevated optic disc with blurred margins H .","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014OPHTHALMOLOGY SEC TION III 555 Retinal disorders (continued) ABCD E FGH Retinoblastoma Most common intraocular malignancy in children. Arises from immature retinal cells A . A Caused by mutations to both RB1 tumor suppressor genes on chromosome 13, which normally impede G1 \u008e\u00a0S phase progression. Can be sporadic or familial (loss of heterozygosity). Presents with leukocoria, strabismus, nystagmus, eye redness. Leukocoria Loss (whitening) of the red reflex. Important causes in children include retinoblastoma A , A congenital cataract. Uveitis Inflammation of uvea; specific name based on location within affected eye. Anterior uveitis: iritis; A posterior uveitis: choroiditis and\/or retinitis. May have hypopyon (accumulation of pus in anterior chamber A ) or conjunctival redness. Associated with systemic inflammatory disorders (eg, sarcoidosis, Beh\u00e7et syndrome, juvenile idiopathic arthritis, HLA-B27\u2013associated conditions). uploaded by medbooksvn","556 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014OPHTHALMOLOGY Pupillary control Constriction, parasympathetic: Miosis \u0083\t 1st neuron: Edinger-Westphal nucleus to ciliary ganglion via CN III Pupillary light reflex \u0083\t 2nd neuron: short ciliary nerves to sphincter pupillae muscles Mydriasis Short ciliary nerves shorten the pupil diameter. Light in either retina sends a signal via CN II Visual \ufb01eld L eye Visual \ufb01eld R eye to pretectal nuclei (dashed lines in image) in midbrain that activates bilateral Edinger- Light Nasal Light Sphincter Westphal nuclei; pupils constrict bilaterally retina pupillae (direct and consensual reflex). muscles Temporal Result: illumination of 1 eye results in bilateral retina Optic nerve Ciliary pupillary constriction. (CN II) ganglion Optic chiasm Oculomotor nerve (CN III) Edinger- Westphal nucleus Lateral geniculate nucleus Pretectal nuclei Dilation, sympathetic: \u0083\t 1st neuron: hypothalamus to ciliospinal center of Budge (C8\u2013T2) \u0083\t 2nd neuron: exit at T1 to superior cervical ganglion (travels along cervical sympathetic chain near lung apex, subclavian vessels) \u0083\t 3rd neuron: plexus along internal carotid, through cavernous sinus; enters orbit as long ciliary nerve to pupillary dilator muscles. Sympathetic fibers also innervate smooth muscle of eyelids (minor retractors) and sweat glands of forehead and face. Long ciliary nerves make the pupil diameter longer. Relative afferent Also called Marcus Gunn pupil. Extent of pupillary constriction differs when light is shone in one pupillary defect eye at a time due to unilateral or asymmetric lesions of afferent limb of pupillary reflex (eg, retina, optic nerve). When light shines into a normal eye, constriction of the ipsilateral eye (direct reflex) and contralateral eye (consensual reflex) is observed. When light is swung from a normal eye to an affected eye, both pupils dilate instead of constricting.","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014OPHTHALMOLOGY SEC TION III 557 Horner syndrome Sympathetic denervation of face: Hypothalamus Ophthalmic division \u0083\t \u0007Ptosis (slight drooping of eyelid: superior of trigeminal nerve Ocular motility tarsal muscle) Internal \u0083\t M\u0007 iosis (pupil constriction) carotid Long ciliary nerve Superior \u0083\t Anhidrosis (absence of sweating) and artery rectus absence of flushing of affected side of face First neuron To sweat glands Lateral Synapse in of forehead rectus Associated with lesions along the sympathetic lateral horn To smooth muscle of eyelid Inferior chain: Spinal cord To pupillary dilator \u0083\t 1st neuron: pontine hemorrhage, lateral To sweat glands of face oblique medullary syndrome, spinal cord lesion External carotid artery above T1 (eg, Brown-S\u00e9quard syndrome, Third neuron A late-stage syringomyelia) Superior cervical ganglion \u0083\t 2nd neuron: stellate ganglion compression Strabismus by Pancoast tumor Second neuron \u0083\t 3rd neuron: carotid dissection (painful); anhidrosis is usually absent Superior Superior Superior CN VI innervates the Lateral Rectus. oblique rectus oblique CN IV innervates the Superior Oblique. CN\u2008III innervates the Rest. Trochlea Medial Trochlea The \u201cchemical formula\u201d LR6SO4R3. rectus Medial SR\u2083 SR\u2083 IO\u2083 SR\u2083 rectus SR\u2083 Inferior Lateral LR\u2086 MR\u2083 LR\u2086 rectus rectus RL Inferior Inferior rectus oblique IR\u2083 IR\u2083 SO\u2084 IR\u2083 IR\u2083 Obliques go Opposite (left SO and IO tested with patient looking right) IOU: IO tested looking Up Blowout fracture\u2014orbital floor fracture; usually caused by direct trauma to eyeball or intraorbital rim. \u008f risk of IR muscle A and\/or orbital fat entrapment. May lead to infraorbital nerve injury Eye misalignment (\u201ccrossed eyes\u201d). Deviation Amblyopia (\u201clazy eye\u201d)\u2014\u0090\u00a0visual acuity due of eye toward the nose (esotropia) is the most to maldevelopment of visual cortex. Caused common type of strabismus in children. by abnormal visual experience early in life (eg,\u00a0due to strabismus). Typically unilateral. Complications include amblyopia, diplopia, adverse psychosocial impact. uploaded by medbooksvn","558 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014OPHTHALMOLOGY Cranial nerve III, IV, VI palsies CN III damage CN III has both motor (central) and Motor = middle (central) parasympathetic (peripheral) components. Parasympathetic = peripheral CN III Common causes include: A \u0083\t Ischemia \u008e\u00a0pupil sparing (motor fibers affected more than parasympathetic fibers) B \u0083\t Uncal herniation \u008e\u00a0coma \u0083\t PCom aneurysm \u008e\u00a0sudden-onset headache \u0083\t Cavernous sinus thrombosis \u008e\u00a0proptosis, involvement of CNs IV, V1\/V2, VI \u0083\t Midbrain stroke \u008e\u00a0contralateral hemiplegia Motor output to extraocular muscles\u2014affected primarily by vascular disease (eg, diabetes mellitus: glucose \u008e sorbitol) due to \u0090 diffusion of oxygen and nutrients to the interior (middle) fibers from compromised vasculature that resides on outside of nerve. Signs: ptosis, \u201cdown-and-out\u201d gaze. Parasympathetic output\u2014fibers on the periphery are first affected by compression (eg, PCom aneurysm, uncal herniation). Signs: diminished or absent pupillary light reflex, \u201cblown pupil\u201d often with \u201cdown-and-out\u201d gaze A . CN IV damage Pupil is higher in the affected eye B . Characteristic head tilt to contralateral\/ unaffected side to compensate for lack of intorsion in affected eye. Can\u2019t see the floor with CN IV damage (eg, difficulty going down stairs, reading). CN VI damage Affected eye unable to abduct C and is displaced C medially in primary position of gaze.","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014OPHTHALMOLOGY SEC TION III 559 Visual field de ects 1.\u2002 Right anopia (monocular vision loss) Defect in visual \ufb01eld of: L eye R eye 2.\u2002 Bitemporal hemianopia 1 Macula LR (pituitary lesion, chiasm) Central scotoma 3.\u2002 Left homonymous hemianopia (macular degeneration) 4.\u2002 Left upper quadrantanopia 2 Optic nerve (right temporal lesion, MCA) Left anopia 5.\u2002 Left lower quadrantanopia 3 Optic chiasm (right parietal lesion, MCA) Bitemporal hemianopia 6.\u2002 Left hemianopia with macular sparing 4 Optic tract (right occipital lesion, PCA) Right homonymous hemianopia 7.\u2002 Central scotoma (eg, macular degeneration) 5 Meyer loop Ventral optic radiation (Meyer loop)\u2014lower Right upper quadrantanopia retina; travels through temporal lobe; loops (left temporal lesion) around inferior horn of lateral ventricle. 6 Dorsal optic radiation Dorsal optic radiation\u2014superior retina; travels Right lower quadrantanopia through parietal lobe. (left temporal lesion) 4 ( 7 if PCA infarct) Visual cortex Right hemianopia with macular sparing Note: When an image hits 1\u00b0 visual cortex, it is upside down and left-right reversed. Cavernous sinus Collection of venous sinuses on either side of pituitary. Blood from eye and superficial cortex \u008e\u00a0cavernous sinus \u008e internal jugular vein. CNs III, IV, V1, V2, and VI plus postganglionic sympathetic pupillary fibers en\u00a0route to orbit all pass through cavernous sinus. Cavernous portion of internal carotid artery is also here. Cavernous sinus syndrome\u2014presents with variable ophthalmoplegia (eg, CN III and CN VI), \u0090\u00a0corneal sensation, Horner syndrome and occasional decreased maxillary sensation. 2\u00b0 to pituitary tumor mass effect, carotid-cavernous fistula, or cavernous sinus thrombosis related to infection (spread due to lack of valves in dural venous sinuses). 3rd ventricle Anterior cerebral a. Internal carotid a. Optic chiasma (CN II) Subarachnoid space Oculomotor n. (CN III) Trochlear n. (CN IV) Pituitary Cavernous sinus Ophthalmic n. (CN V1) Sphenoid Pia Maxillary n. (CN V2) sinus Arachnoid Dura Abducens n. (CN VI) uploaded by medbooksvn","560 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014OPHTHALMOLOGY Internuclear Medial longitudinal fasciculus (MLF): pair of MLF in MS. ophthalmoplegia tracts that interconnect CN\u00a0VI and CN III When looking left, the left nucleus of CN VI nuclei. Coordinates both eyes to move in same fires, which contracts the left lateral rectus and horizontal direction. Highly myelinated (must stimulates the contralateral (right) nucleus of communicate quickly so eyes move at same CN III via the right MLF to contract the right time). Lesions may be unilateral or bilateral medial rectus. (latter classically seen in multiple sclerosis, Directional term (eg, right INO, left INO) refers stroke). to the eye that is unable to adduct. Lesion in MLF = internuclear ophthalmoplegia INO = Ipsilateral adduction failure, Nystagmus (INO), a conjugate horizontal gaze palsy. Opposite. Lack of communication such that when CN\u00a0VI nucleus activates ipsilateral lateral rectus, contralateral CN III nucleus does not stimulate medial rectus to contract. AbduRcitgihnt gfrontal eye displays nystagmus (CN VI overfires to eye \ufb01eld stimulate CNVo\u00a0lIuItnoIt)al.reyfCtgaozne vergence normal. L R Right frontal Right INO (right MLF lesion) Lateral Medial eye \ufb01eld rectus Volunrtearcytugsaze to left Lateral CNL VI R CN III rectus Medial rectus MidbrainCN VI CN III Oculomotor Midbrain (CN III) nucleus Pons Pons Right gaze Medulla Oculomotor Impaired adduction Nystagmus (convergence normal) (CNRIiIIg) hnutcMleLuFs Left gaze Paramedian pontine reticular formation (PPRF) RigAhbt dMuLcFens Par(aCmNeVdIia) nnupcolnetuinse reticular formation (PPRF) Abducens (CN VI) nucleus Medulla","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pharmacology SEC TION III 561 ` \u2009NEUROLOGY \u2014 P H A RM A C OLOGY Anticonvulsants COMMON ADVERSE EFFECTS RARE BUT SERIOUS ADVERSE EFFECTS MECHANISM Sedation, dizziness, diplopia, SJS, DRESS, hepatotoxicity, gingival hypertrophy, rash, neuropathy, osteoporosis, Narrow spectrum (focal seizures) hirsutism, drug interactions folate depletion, teratogenicity Phenytoin (CYP450 induction) SJS, DRESS, hepatotoxicity, Carbamazepine Block Na+ channel Sedation, dizziness, diplopia, agranulocytosis, aplastic vomiting, diarrhea, SIADH, anemia, folate depletion, Gabapentinoids Block Ca2+ channel rash, drug interactions teratogenicity Gabapentin, (CYP450 induction) pregabalin Hepatotoxicity, pancreatitis, Sedation, dizziness, ataxia, teratogenicity Narrow spectrum (absence seizures only) weight gain SJS, DRESS Ethosuximide Blocks Ca2+ channel Sedation, dizziness, vomiting Neuropsychiatric (eg, Broad spectrum (focal and generalized seizures) Sedation, dizziness, vomiting, psychosis) weight gain, hair loss, easy Kidney stones, angle-closure Valproate Blocks Na+ channel bruising, drug interactions Blocks Ca2+ channel (CYP450 inhibition) glaucoma Blocks GABA transaminase Sedation, dizziness, rash Lamotrigine Blocks Na+ channel Sedation, dizziness, fatigue Levetiracetam Blocks Synaptic Vesicle protein Sedation, dizziness, mood Topiramate 2A (SV2A) disturbance (eg, depression), weight loss, paresthesia Blocks Na+ channel Potentiates GABAA receptor uploaded by medbooksvn","562 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pharmacology Anticonvulsants (continued) EXCITATORY NEURON Na+ CHANNEL BLOCKERS Action Ca\u00b2+ CHANNEL BLOCKERS potential Phenytoin Gabapentinoids Carbamazepine Voltage-gated Ethosuximide Valproate Na+ channel Valproate Lamotrigine Na+ Topiramate Voltage-gated Depolarization Ca2+ channel SV2A RECEPTOR BLOCKER Ca2+ Glutamate vesicle Levetiracetam release SV2A receptor GABAA AGONISTS Na+ Ca2+ AMPA NMDA Benzodiazepines receptor receptor Phenobarbital recGeApBtAorA Cl_ Topiramate Depolarization Action Cl_ potential GABA GABA POST-SYNAPTIC GAD reuptake NEURON receptor Glutamate INHIBITORY Succinic semi- GABA GABA NEURON aldehyde (SSA) transaminase GABA TRANSAMINASE BLOCKER Valproate","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pharmacology SEC TION III 563 Barbiturates Phenobarbital, pentobarbital. MECHANISM Facilitate GABAA action by \u008f duration of Cl\u2212 channel opening, thus \u0090 neuron firing (barbidurates CLINICAL USE \u008f duration). ADVERSE EFFECTS Sedative for anxiety, seizures, insomnia. Benzodiazepines Respiratory and cardiovascular depression (can be fatal); CNS depression (can be exacerbated by MECHANISM alcohol use); dependence; drug interactions (induces cytochrome P-450). CLINICAL USE Overdose treatment is supportive (assist respiration and maintain BP). ADVERSE EFFECTS Contraindicated in porphyria. Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam. Facilitate GABAA action by \u008f frequency of Cl\u2013 channel opening (\u201cfrenzodiazepines\u201d \u008f\u00a0frequency). \u0090\u00a0REM sleep. Most have long half-lives and active metabolites (exceptions [ATOM]: Alprazolam, Triazolam, Oxazepam, and Midazolam are short acting \u008e higher addictive potential). Anxiety, panic disorder, spasticity, status epilepticus (lorazepam, diazepam, midazolam), eclampsia, medically supervised withdrawal (eg, alcohol\/DTs; long-acting chlordiazepoxide and diazepam are preferred), night terrors, sleepwalking, general anesthetic (amnesia, muscle relaxation), hypnotic (insomnia). Lorazepam, Oxazepam, and Temazepam can be used for those with liver disease who drink a LOT due to minimal first-pass metabolism. Dependence, additive CNS depression effects with alcohol and barbiturates (all bind the GABAA receptor). Less risk of respiratory depression and coma than with barbiturates. Treat overdose with flumazenil (competitive antagonist at GABA benzodiazepine receptor). Can precipitate seizures by causing acute benzodiazepine withdrawal. uploaded by medbooksvn","564 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pharmacology Insomnia therapy MECHANISM ADVERSE EFFECTS NOTES AGENT Examples: Zolpidem, Ataxia, headaches, confusion These ZZZs put you to sleep Zaleplon, esZopiclone Cause only modest day-after Short duration due to rapid Nonbenzodiazepine hypnotics Act via the BZ1 subtype of psychomotor depression and metabolism by liver enzymes; GABA receptor few amnestic effects (vs older effects reversed by flumazenil sedative-hypnotics) \u0090\u00a0dependency risk and Suvorexant Orexin (hypocretin) receptor \u0090\u00a0sleep cycle disturbance (vs antagonist CNS depression (somnolence), benzodiazepine hypnotics) headache, abnormal sleep- Ramelteon Melatonin receptor agonist: related activities Contraindications: narcolepsy, binds MT1 and MT2 in combination with strong suprachiasmatic nucleus Dizziness, nausea, fatigue, CYP3A4 inhibitors headache Not recommended in patients with liver disease Limited risk of dependency No known risk of dependency Triptans Sumatriptan MECHANISM 5-HT1B\/1D agonists. Inhibit trigeminal nerve activation, prevent vasoactive peptide release, induce vasoconstriction. CLINICAL USE ADVERSE EFFECTS Acute migraine, cluster headache attacks. A sumo wrestler trips and falls on their head. Coronary vasospasm (contraindicated in patients with CAD or vasospastic angina), mild paresthesia, serotonin syndrome (in combination with other 5-HT agonists).","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pharmacology SEC TION III 565 Parkinson disease The most effective treatments are non-ergot dopamine agonists which are usually started in therapy younger patients, and levodopa (with carbidopa) which is usually started in older patients. Deep brain stimulation of the STN or GPi may be helpful in advanced disease. STRATEGY AGENTS Dopamine agonists Non-ergot (preferred)\u2014pramipexole, ropinirole; toxicity includes nausea, impulse control disorder (eg, gambling), postural hypotension, hallucinations, confusion, sleepiness, edema. Ergot\u2014bromocriptine; rarely used due to toxicity. \u008f dopamine availability Amantadine (\u008f\u00a0dopamine release and \u0090\u00a0dopamine reuptake); mainly used to reduce levodopa- \u008f l-DOPA availability induced dyskinesias; toxicity = peripheral edema, livedo reticularis, ataxia. Prevent dopamine Agents prevent peripheral (pre-BBB) l-DOPA degradation \u008e\u00a0\u008f\u00a0l-DOPA entering CNS \u008e\u00a0\u008f\u00a0central breakdown l-DOPA available for conversion to dopamine. \u0083\t Levodopa (l-DOPA)\/carbidopa\u2014carbidopa blocks peripheral conversion of l-DOPA to Curb excess dopamine by inhibiting DOPA decarboxylase. Also reduces adverse effects of peripheral cholinergic activity l-DOPA conversion into dopamine (eg, nausea, vomiting). \u0083\t Entacapone and tolcapone prevent peripheral l-DOPA degradation to 3-O-methyldopa (3\u2011OMD) by inhibiting COMT. Used in conjunction with levodopa. Agents act centrally (post-BBB) to inhibit breakdown of dopamine. \u0083\t Selegiline, rasagiline\u2014block conversion of dopamine into DOPAC by selectively inhibiting MAO-B, which is more commonly found in the Brain than in the periphery. \u0083\t Tolcapone\u2014crosses BBB and blocks conversion of dopamine to 3-methoxytyramine (3-MT) in the brain by inhibiting central COMT. Benztropine, trihexyphenidyl (Antimuscarinic; improves tremor and rigidity but has little effect on bradykinesia in Parkinson disease). Tri Parking my Mercedes-Benz. \u2003 DOPA Dopamine CIRCULATION 3-OMD DECARBOXYLASE INHIBITOR \u2013 L-DOPA \u2013 COMT INHIBITORS Carbidopa DDC (peripheral) COMT BLOOD- Entacapone BRAIN Tolcapone BARRIER L-DOPA COMT INHIBITOR DDC (central) PRESYNAPTIC Dopamine COMT \u2013 Tolcapone TERMINAL FROM THE SUBSTANTIA NIGRA 3-MT MAO TYPE B DOPAC INHIBITORS DOPAMINE Selegiline AVAILABILITY Autoregulatory \u2013 Rasagiline Amantadine receptor Reuptake + POSTSYNAPTIC Dopamine receptors + DOPAMINE AGONISTS TERMINAL IN THE STRIATUM Pramipexole (non-ergot) Ropinirole (non-ergot) Bromocriptine (ergot) uploaded by medbooksvn","566 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pharmacology Carbidopa\/levodopa \u008f dopamine in brain. Unlike dopamine, l-DOPA can cross BBB and is converted by DOPA decarboxylase in the CNS to dopamine. Carbidopa, a peripheral DOPA decarboxylase inhibitor MECHANISM that cannot cross BBB, is given with l-DOPA to \u008f bioavailability of l-DOPA in the brain and to limit peripheral adverse effects. CLINICAL USE ADVERSE EFFECTS Parkinson disease. Nausea, hallucinations, postural hypotension. With progressive disease, l-DOPA can lead to \u201con- off\u201d phenomenon with improved mobility during \u201con\u201d periods, then impaired motor function during \u201coff\u201d periods when patient responds poorly to l-DOPA or medication wears off. Neurodegenerative disease therapy DISEASE AGENT MECHANISM NOTES Alzheimer disease Donepezil, rivastigmine, AChE inhibitor 1st-line treatment galantamine Adverse effects: nausea, dizziness, NMDA receptor antagonist; helps Memantine prevent excitotoxicity (mediated by insomnia; contraindicated Ca2+) in patients with cardiac Amyotrophic lateral Riluzole conduction abnormalities sclerosis \u0090\u00a0neuron glutamate excitotoxicity Dona Riva dances at the gala Huntington disease Deutetrabenazine, Inhibit vesicular monoamine Used for moderate to advanced tetrabenazine transporter (VMAT) \u008e\u00a0\u0090\u00a0dopamine dementia vesicle packaging and release Adverse effects: dizziness, confusion, hallucinations \u008f\u00a0survival Treat Lou Gehrig disease with riLouzole May be used for Huntington chorea and tardive dyskinesia","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pharmacology SEC TION III 567 Local anesthetics Esters\u2014benzocaine, chloroprocaine, cocaine, Local anesthetic Sodium tetracaine. Axonal membrane channel Amides\u2014bupivacaine, lidocaine, mepivacaine, prilocaine, ropivacaine (amides have 2 i\u2019s in name). Cell interior MECHANISM Block neurotransmission via binding to voltage-gated Na+ channels on inner portion of the channel along nerve fibers. Most effective in rapidly firing neurons. 3\u00b0 amine local anesthetics penetrate CLINICAL USE membrane in uncharged form, then bind to ion channels as charged form. ADVERSE EFFECTS Can be given with vasoconstrictors (usually epinephrine) to enhance block duration of action by \u0090\u00a0systemic absorption. In infected (acidic) tissue, alkaline anesthetics are charged and cannot penetrate membrane effectively \u008e need more anesthetic. Order of loss: (1) pain, (2) temperature, (3) touch, (4) pressure. Minor surgical procedures, spinal anesthesia. If allergic to esters, give amides. CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension, hypotension, arrhythmias (cocaine), methemoglobinemia (benzocaine, prilocaine). General anesthetics CNS drugs must be lipid soluble (cross the BBB) or be actively transported. Inhaled anesthetics Drugs with \u0090 solubility in blood (eg, nitrous oxide [N2O]) = rapid induction and recovery times. Sevoflurane Drugs with \u008f solubility in lipids (eg, isoflurane) = \u008f potency. Desflurane Isoflurane MAC = Minimum Alveolar Concentration (of inhaled anesthetic) required to prevent 50% of N2O subjects from moving in response to noxious stimulus (eg, skin incision). Potency = 1\/MAC. Intravenous anesthetics Propofol MECHANISM ADVERSE EFFECTS\/NOTES Etomidate Mechanism unknown Respiratory depression, \u0090 cough reflex Ketamine Myocardial depression, \u0090 BP \u008f cerebral blood flow (\u008f ICP), \u0090 metabolic rate \u0090 skeletal and smooth muscle tone Postoperative nausea and vomiting Malignant hyperthermia Diffusion into and expansion (N2O) of gas-filled cavities (eg, pneumothorax); very low potency Potentiates GABAA receptor Respiratory depression, \u0090 BP; most commonly Inhibits NMDA receptor used IV agent for induction of anesthesia Potentiates GABAA receptor Acute adrenal insufficiency, postoperative Inhibits NMDA receptor nausea and vomiting; hemodynamically neutral Sympathomimetic: \u008f BP, \u008f HR, \u008f cerebral blood flow (\u008f ICP), bronchodilation Psychotomimetic: hallucinations, vivid dreams uploaded by medbooksvn","568 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pharmacology Neuromuscular Muscle paralysis in surgery or mechanical ventilation. Selective for Nm nicotinic receptors at blocking drugs neuromuscular junction but not autonomic Nn receptors. Depolarizing Succinylcholine\u2014strong Nm nicotinic receptor agonist; produces sustained depolarization and neuromuscular prevents muscle contraction. blocking drugs Reversal of blockade: Nondepolarizing \u0083\t Phase I (prolonged depolarization)\u2014no antidote. Block potentiated by cholinesterase inhibitors. neuromuscular \u0083\t Phase II (repolarized but blocked; Nm nicotinic receptors are available, but desensitized)\u2014may blocking drugs be reversed with cholinesterase inhibitors. Malignant Complications include hypercalcemia, hyperkalemia, malignant hyperthermia. \u008f\u00a0risk of prolonged hyperthermia muscle paralysis in patients with pseudocholinesterase deficiency. Atracurium, cisatracurium, pancuronium, rocuronium, vecuronium\u2014competitive Nm nicotinic receptor antagonist. Reversal of blockade\u2014sugammadex or cholinesterase inhibitors (eg, neostigmine). Anticholinergics (eg, atropine, glycopyrrolate) are given with cholinesterase inhibitors to prevent muscarinic effects (eg, bradycardia). Rare, life-threatening, hypermetabolic condition caused by the administration of potent inhaled anesthetics (sevoflurane, desflurane, isoflurane) or succinylcholine in susceptible individuals. Susceptibility to malignant hyperthermia is caused by de novo or inherited (autosomal dominant) mutations to ryanodine (RYR1) or dihydropyridine receptors (DHPR). \u008f\u00a0\u008f\u00a0Ca2+ release from sarcoplasmic reticulum \u008e\u00a0sustained muscle contraction \u008e\u00a0hypercapnia, tachycardia, masseter\/generalized muscle rigidity, rhabdomyolysis, hyperthermia. Treatment: dantrolene (ryanodine receptor antagonist).","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pharmacology SEC TION III 569 Skeletal muscle relaxants DRUG MECHANISM CLINICAL USE NOTES Baclofen GABAB receptor agonist in Muscle spasticity, dystonia, Acts on the back (spinal cord) spinal cord multiple sclerosis May cause sedation Cyclobenzaprine Acts within CNS, mainly at the Muscle spasms Centrally acting brainstem Structurally related to TCAs Malignant hyperthermia May cause anticholinergic Dantrolene Prevents release of Ca2+ from (toxicity of inhaled anesthetics sarcoplasmic reticulum of and succinylcholine) and adverse effects, sedation skeletal muscle by inhibiting neuroleptic malignant the ryanodine receptor syndrome (toxicity of Acts directly on muscle antipsychotics) Tizanidine \u03b12 agonist, acts centrally Muscle spasticity, multiple sclerosis, ALS, cerebral palsy Opioid analgesics Act as agonists at opioid receptors (\u03bc = \u03b2-endorphin, \u03b4 = enkephalin, \u03ba = dynorphin) to modulate synaptic transmission\u2014close presynaptic Ca2+ channels, open postsynaptic K+ channels MECHANISM \u008e\u00a0\u0090\u00a0synaptic transmission. Inhibit release of ACh, norepinephrine, 5-HT, glutamate, substance P. EFFICACY Full agonist: morphine, meperidine (long acting), methadone, codeine (prodrug; activated by CYP2D6), fentanyl. CLINICAL USE Partial agonist: buprenorphine. ADVERSE EFFECTS Mixed agonist\/antagonist: butorphanol, nalbuphine. Antagonist: naloxone, naltrexone, methylnaltrexone. Tramadol Moderate to severe or refractory pain, diarrhea (loperamide, diphenoxylate), acute pulmonary MECHANISM edema, maintenance programs for opiate use disorder (methadone, buprenorphine + naloxone), CLINICAL USE neonatal abstinence syndrome (methadone, morphine). ADVERSE EFFECTS Nausea, vomiting, pruritus (histamine release), opiate use disorder, respiratory depression, constipation, sphincter of Oddi spasm, miosis (except meperidine \u008e\u00a0mydriasis), additive CNS depression with other drugs. Tolerance does not develop to miosis and constipation. Treat toxicity with naloxone and prevent relapse with naltrexone once detoxified. Very weak opioid agonist; also inhibits the reuptake of norepinephrine and serotonin. Chronic pain. Similar to opioids; decreases seizure threshold; serotonin syndrome. uploaded by medbooksvn","570 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pharmacology Butorphanol, nalbuphine MECHANISM \u03bc-opioid receptor partial agonists and \u03ba-opioid receptor full agonists. CLINICAL USE Analgesia for severe pain (eg, labor). NOTES Mixed opioid agonists\/antagonists cause less respiratory depression than full opioid agonists. Can cause opioid withdrawal symptoms if patient is also taking full opioid agonist (due to competition for opioid receptors). Not easily reversed with naloxone. Capsaicin Naturally found in hot peppers. Excessive stimulation and desensitization of nociceptive fibers \u008e \u0090 substance P release \u008e \u0090 pain. MECHANISM Musculoskeletal and neuropathic pain. CLINICAL USE Glaucoma therapy \u0090\u00a0IOP via \u0090\u00a0amount of aqueous humor (inhibit synthesis\/secretion or \u008f\u00a0drainage). \u201c\u03b2\u03b1D humor may not be politically correct.\u201d DRUG CLASS EXAMPLES MECHANISM ADVERSE EFFECTS \u03b2-blockers \u03b1-agonists Timolol, betaxolol, carteolol \u0090\u00a0aqueous humor synthesis No pupillary or vision changes Diuretics Epinephrine (\u03b11), \u0090\u00a0aqueous humor synthesis via Mydriasis (\u03b11); do not use in Prostaglandins apraclonidine, vasoconstriction (epinephrine) closed-angle glaucoma Cholinomimetics (M3) brimonidine\u00a0(\u03b12) \u0090\u00a0aqueous humor synthesis Blurry vision, ocular (apraclonidine, brimonidine) hyperemia, foreign body sensation, ocular allergic \u008f\u00a0outflow of aqueous humor via reactions, ocular pruritus uveoscleral pathway Acetazolamide \u0090\u00a0aqueous humor synthesis No pupillary or vision changes via inhibition of carbonic anhydrase Bimatoprost, latanoprost \u008f\u00a0outflow of aqueous humor via Darkens color of iris (PGF2\u03b1) \u0090\u00a0resistance of flow through (browning), eyelash growth uveoscleral pathway Direct: pilocarpine, carbachol \u008f\u00a0outflow of aqueous humor via Miosis (contraction of pupillary Indirect: physostigmine, contraction of ciliary muscle sphincter muscles) and echothiophate and opening of trabecular cyclospasm (contraction of meshwork ciliary muscle) Use pilocarpine in acute angle closure glaucoma\u2014very effective at opening meshwork into canal of Schlemm","HIGH-YIELD PRINCIPLES IN Psychiatry \u201cWords of comfort, skillfully administered, are the oldest therapy known to `\tPsychology\t 572 man.\u201d `\tPathology\t 575 `\tPharmacology\t 592 \u2014Louis Nizer \u201cPsychiatry at its best is what all medicine needs more of\u2014humanity, art, listening, and sympathy.\u201d \u2014Susannah Cahalan \u201cIt\u2019s time to tell everyone who\u2019s dealing with a mental health issue that they\u2019re not alone, and that getting support and treatment isn\u2019t a sign of weakness, it\u2019s a sign of strength.\u201d \u2014Michelle Obama \u201cI have schizophrenia. I am not schizophrenia. I am not my mental illness. My illness is a part of me.\u201d \u2014Jonathan Harnisch This chapter encompasses overlapping areas in psychiatry, psychology, sociology, and psychopharmacology. High-yield topics include schizo\u00ad phrenia, mood disorders, eating disorders, personality disorders, somatic symptom disorders, substance use disorders, and antipsychotics. Know the DSM-5 criteria for diagnosing common psychiatric disorders. 571 uploaded by medbooksvn","572 SECTION III Psychiatry\u2003 \uf07d\u2009Psychiatry\u2014PSYCHology ` \u2009P SYCHIATRY \u2014 P SYCHOLOGY Classical conditioning Learning in which a natural response Usually elicits involuntary responses. (salivation) is elicited by a conditioned, Pavlov\u2019s classical experiments with dogs\u2014 or learned, stimulus (bell) that previously was presented in conjunction with an ringing the bell provoked salivation. unconditioned stimulus (food). Operant conditioning Learning in which a particular action is elicited because it produces a punishment or reward. Reinforcement Usually elicits voluntary responses. Punishment Target behavior (response) is followed by desired Skinner operant conditioning quadrants: Extinction reward (positive reinforcement) or removal of Increase behavior Decrease behavior aversive stimulus (negative reinforcement). Repeated application of aversive stimulus Remove a Add a Positive Positive (positive punishment) or removal of desired stimulus stimulus reinforcement punishment reward (negative punishment) to extinguish unwanted behavior. Negative Negative reinforcement punishment Discontinuation of reinforcement (positive or negative) eventually eliminates behavior. Can occur in operant or classical conditioning. Transference and countertransference Transference Patient projects feelings about formative or other important persons onto physician (eg, psychiatrist is seen as parent). Countertransference Physician projects feelings about formative or other important persons onto patient (eg, patient reminds physician of younger sibling). Ego defenses Thoughts and behaviors (voluntary or involuntary) used to resolve conflict and prevent undesirable feelings (eg, anxiety, depression). IMMATURE DEFENSES DESCRIPTION EXAMPLE Acting out Subconsciously coping with stressors or A patient skips therapy appointments after deep Denial emotional conflict using actions rather than discomfort from dealing with his past. reflections or feelings. Displacement Avoiding the awareness of some painful reality. A patient with cancer plans a full-time work Dissociation schedule despite being warned of significant fatigue during chemotherapy. Redirection of emotions or impulses to a neutral After being reprimanded by her principal, a person or object (vs projection). frustrated teacher returns home and criticizes her wife\u2019s cooking instead of confronting the principal directly. Temporary, drastic change in personality, A survivor of sexual abuse sees the abuser and memory, consciousness, or motor behavior to suddenly becomes numb and detached. avoid emotional stress. Patient has incomplete or no memory of traumatic event.","Psychiatry\u2003 \uf07d\u2009Psychiatry\u2014PSYCHology SECTION III 573 Ego defenses (continued) IMMATURE DEFENSES DESCRIPTION EXAMPLE Fixation Partially remaining at a more childish level of A college student studying for a stressful exam development (vs regression). begins sucking her thumb. Idealization Expressing extremely positive thoughts of self A patient boasts about his physician and his and others while ignoring negative thoughts. accomplishments while ignoring any flaws. Identification Largely unconscious assumption of the A resident starts putting her stethoscope in her characteristics, qualities, or traits of another pocket like her favorite attending, instead of person or group. wearing it around her neck like before. Intellectualization Using facts and logic to emotionally distance A patient diagnosed with cancer discusses the oneself from a stressful situation. pathophysiology of the disease. Isolation (of affect) Separating feelings from ideas and events. Describing murder in graphic detail with no emotional response. Passive aggression Demonstrating hostile feelings in a nonconfrontational manner; showing indirect A disgruntled employee is repeatedly late to Projection opposition. work, but won\u2019t admit it is a way to get back at Rationalization the manager. Attributing an unacceptable internal impulse to Reaction formation an external source (vs displacement). A man who wants to cheat on his wife accuses Regression his wife of being unfaithful. Asserting plausible explanations for events that Repression actually occurred for other reasons, usually to An employee who was recently fired claims that avoid self-blame. the job was not important anyway. Replacing a warded-off idea or feeling with an A stepfather treats a child he resents with emphasis on its opposite (vs sublimation). excessive nurturing and overprotection. Involuntarily turning back the maturational A previously toilet-trained child begins clock to behaviors previously demonstrated bedwetting again following the birth of a under stress (vs fixation). sibling. Involuntarily withholding an idea or feeling A 20-year-old does not remember going to from conscious awareness (vs suppression). counseling during his parents\u2019 divorce 10 years earlier. Splitting Believing that people are either all good or all bad at different times due to intolerance of A patient says that all the nurses are cold and MATURE DEFENSES ambiguity. Common in borderline personality insensitive, but the physicians are warm and disorder. Borders split countries. friendly. Sublimation Replacing an unacceptable wish with a course A teenager\u2019s aggression toward her parents Altruism of action that is similar to the wish but socially because of their high expectations is channeled acceptable (vs reaction formation). into excelling in sports. Suppression Humor Alleviating negative feelings via unsolicited A mafia boss makes a large donation to charity. generosity, which provides gratification (vs reaction formation). An athlete focuses on other tasks to prevent worrying about an important upcoming match. Intentionally withholding an idea or feeling from conscious awareness (vs repression); temporary. A nervous medical student jokes about the boards. Lightheartedly expressing uncomfortable feelings to shift the internal focus away from the distress. Mature adults wear a SASH. uploaded by medbooksvn","574 SECTION III Psychiatry\u2003 \uf07d\u2009Psychiatry\u2014PSYCHology Grief Natural feeling that occurs in response to the death of a loved one. Symptoms and trajectory vary for each individual, are specific to each loss, and do not follow a fixed series of stages. In addition to guilt, sadness, and yearning, patients may experience somatic symptoms, hallucinations of the deceased, and\/or transient episodes of wishing they had died with or instead of their loved one. Typical acute grief is time limited (adaptations within 6 months) and is not a disorder. Prolonged grief disorder\u2014diagnosed if thoughts are persistent and prolonged, significantly impair functioning, and do not meet criteria for another disorder (eg, major depressive disorder [MDD]). Normal infant and Milestone dates are ranges that have been approximated and vary by source. Children not meeting child development milestones may need assessment for potential developmental delay. AGE MOTOR SOCIAL VERBAL\/COGNITIVE Infant Parents Start Observing, 0\u201312 mo Primitive reflexes disappear\u2014 Social smile (by 2 mo) Orients\u2014first to voice (by Toddler Moro, rooting, palmar, Stranger anxiety (by 6 mo) 4\u00a0mo), then to name and 12\u201336 mo Babinski (Mr. Peanut Butter) Separation anxiety (by 9 mo) gestures (by 9\u00a0mo) Preschool Posture\u2014lifts head up prone (by Object permanence (by 9 mo) 3\u20135 yr 1\u00a0mo), rolls and sits (by 6\u00a0mo), Oratory\u2014says \u201cmama\u201d and crawls (by 8 mo), stands (by 10\u00a0mo), walks (by 12\u201318 mo) \u201cdada\u201d (by 10 mo) Picks\u2014passes toys hand to hand (by 6 mo), Pincer grasp (by 10\u00a0mo) Points to objects (by 12 mo) Child Rearing Working, Cruises, takes first steps (by Recreation\u2014parallel play (by Words\u2014uses 50-200 words (by 12\u00a0mo) 24\u201336\u00a0mo) 2\u00a0yr), uses 300+ words (by 3 yr) Climbs stairs (by 18 mo) Rapprochement\u2014moves away Cubes stacked (number) from and returns to parent (by 24 mo) = age (yr) \u00d7 3 Cutlery\u2014feeds self with fork Realization\u2014core gender identity formed (by 36 mo) and spoon (by 20 mo) Kicks ball (by 24 mo) Don\u2019t Forget, they\u2019re still Learning! Drive\u2014tricycle (3 wheels at Freedom\u2014comfortably spends Language\u2014understands 1000 3\u00a0yr) part of day away from parent (3 zeros) words (by 3 yr), (by 3 yr) uses complete sentences and Drawings\u2014copies line or prepositions (by 4 yr) circle, stick figure (by 4 yr) Friends\u2014cooperative play, has imaginary friends (by 4 yr) Legends\u2014can tell detailed Dexterity\u2014hops on one foot stories (by 4 yr) by 4 yr (\u201c4 on one foot\u201d), uses buttons or zippers, grooms self (by 5 yr)","Psychiatry\u2003 \uf07d\u2009Psychiatry\u2014Pathology SECTION III 575 ` \u2009P SYCHIATRY \u2014 PATHOLOGY Child abuse Physical abuse Sexual abuse Emotional abuse STIs, UTIs, and genital, anal, SIGNS Nonaccidental trauma (eg, Babies or young children may fractures, bruises, burns). or oral trauma. Most often, lack a bond with the caregiver EPIDEMIOLOGY Injuries often in different there are no physical signs; but are overly affectionate stages of healing or in sexual abuse should not be with less familiar adults. patterns resembling possible excluded from a differential They may be aggressive implements of injury. diagnosis in the absence of toward children and animals Includes abusive head trauma physical trauma. or unusually anxious. (shaken baby syndrome), Children often exhibit sexual characterized by subdural knowledge or behavior Older children are often hematomas or retinal incongruent with their age. emotionally labile and prone hemorrhages. to angry outbursts. They may Peak incidence 9\u201312 years old. distance themselves from Caregivers may delay seeking caregivers and other children. medical attention for the They can experience vague child or provide explanations somatic symptoms for which inconsistent with the child's a medical cause cannot be developmental stage or found. pattern of injury. ~80% of young adult victims of 40% of deaths related to child child emotional abuse meet abuse or neglect occur in the criteria for \u2265 1 psychiatric children < 1 year old. illness by age 21. Child neglect Failure to provide a child with adequate food, shelter, supervision, education, and\/or affection. Most common form of child maltreatment. Signs: poor hygiene, malnutrition, withdrawal, impaired social\/emotional development, failure to thrive. As with other types of child abuse, suspected child neglect must be reported to local child protective services. Vulnerable child Parents perceive the child as especially susceptible to illness or injury (vs factitious disorder syndrome imposed on another). Usually follows a serious illness or life-threatening event. Can result in missed school or overuse of medical services. uploaded by medbooksvn","576 SECTION III Psychiatry\u2003 \uf07d\u2009Psychiatry\u2014Pathology Childhood and early-onset disorders Attention-deficit Onset before age 12, but diagnosis can only be established after age 4. Characterized by hyperactivity hyperactivity, impulsivity, and\/or inattention in \u2265 2 settings (eg, school, home, places of worship). disorder Normal intelligence, but commonly coexists with difficulties in school. Often persists into adulthood. Commonly coexists with other behavioral, cognitive, or developmental disorders. Autism spectrum Treatment: stimulants (eg, methylphenidate) +\/\u2013 behavioral therapy; alternatives include disorder atomoxetine and \u03b12-agonists (eg, clonidine, guanfacine). Onset in early childhood. Social and communication deficits, repetitive\/ritualized behaviors, restricted interests. May be accompanied by intellectual disability and\/or above average abilities in specific skills (eg, music). More common in males. Associated with \u008f\u00a0head and\/or brain size. Conduct disorder Repetitive, pervasive behavior violating societal norms or the basic rights of others (eg, aggression toward people and animals, destruction of property, theft). After age 18, often reclassified as antisocial personality disorder. Conduct = children, antisocial = adults. Treatment: psychotherapy (eg, cognitive behavioral therapy [CBT]). Disruptive mood Onset before age 10. Severe, recurrent temper outbursts out of proportion to situation. Child is dysregulation constantly angry and irritable between outbursts. Treatment: CBT, stimulants, antipsychotics. disorder Intellectual disability Global cognitive deficits (vs specific learning disorder) that affect reasoning, memory, abstract thinking, judgment, language, learning. Adaptive functioning is impaired, leading to major difficulties with education, employment, communication, socialization, independence. Treatment: psychotherapy, occupational therapy, special education. Intermittent explosive Onset after age 6. Recurrent verbal or physical outbursts representing a failure to control aggressive disorder impulses. Outbursts last < 30 minutes and are out of proportion to provocation and may lead to legal, financial, or social consequences. Episodes are not premeditated and may provide an immediate sense of relief, followed by remorse. Treatment: psychotherapy, SSRIs. Oppositional defiant Pattern of anger and irritability with argumentative, vindictive, and defiant behavior toward disorder authority figures lasting \u2265 6 months. Treatment: psychotherapy (eg, CBT). Selective mutism Onset before age 5. Anxiety disorder lasting \u2265 1 month involving refraining from speech in certain situations despite speaking in other, usually more comfortable situations. Development (eg, speech and language) not typically impaired. Interferes with social, academic, and occupational tasks. Commonly coexists with social anxiety disorder. Treatment: behavioral, family, and play therapy; SSRIs. Separation anxiety Overwhelming fear of separation from home or attachment figure lasting \u2265 4 weeks. Can be disorder normal behavior up to age 3\u20134. May lead to factitious physical complaints to avoid school. Treatment: CBT, play therapy, family therapy. Specific learning Onset during school-age years. Inability to acquire or use information from a specific subject disorder (eg, math, reading, writing) near age-expected proficiency for \u2265 6 months despite focused intervention. General functioning and intelligence are normal (vs intellectual disability). Treatment: academic support, counseling, extracurricular activities. Tourette syndrome Onset before age 18. Sudden, recurrent, nonrhythmic, stereotyped motor (eg, grimacing, shrugging) and vocal (eg, grunting, throat clearing) tics that persist for > 1 year. Coprolalia (involuntary obscene speech) found in some patients. Associated with OCD and ADHD. Treatment: psychoeducation, behavioral therapy. For intractable and distressing tics: tetrabenazine, antipsychotics, \u03b12-agonists.","Psychiatry\u2003 \uf07d\u2009Psychiatry\u2014Pathology SECTION III 577 Orientation Patients\u2019 ability to know the date and time, where they are, and who they are (order of loss: time \u008e\u00a0place \u008e\u00a0person). Common causes of loss of orientation: alcohol, drugs, fluid\/electrolyte imbalance, head trauma, hypoglycemia, infection, nutritional deficiencies, hypoxia. Amnesias Inability to remember things that occurred before a CNS insult. Retrograde amnesia Anterograde amnesia Inability to remember things that occurred after a CNS insult (\u0090\u00a0acquisition of new memory). Korsakoff syndrome Amnesia (anterograde > retrograde) and disorientation caused by vitamin B1 deficiency. Associated with disruption and destruction of the limbic system, especially mammillary bodies and anterior thalamus. Seen in chronic alcohol use as a late neuropsychiatric manifestation of\u00a0Wernicke encephalopathy. Confabulations are characteristic. Dissociative disorders Persistent feelings of detachment or estrangement from one\u2019s own body, thoughts, perceptions, Depersonalization\/ and actions (depersonalization) or one\u2019s environment (derealization). Intact reality testing (vs derealization psychosis). disorder Dissociative amnesia Inability to recall important personal information, usually following severe trauma or stress. May be accompanied by dissociative fugue (abrupt, unexpected travelling away from home). Dissociative identity disorder Formerly called multiple personality disorder. Presence of \u2265 2 distinct identities or personality states, typically with distinct memories and patterns of behavior. More common in females. Associated with history of sexual abuse, PTSD, depression, substance use, borderline personality disorder, somatic symptom disorders. Delirium \u201cWaxing and waning\u201d level of consciousness Delirium = changes in sensorium. with acute onset, \uf090\u00a0attention span, \uf090\u00a0level EEG may show diffuse background rhythm of arousal. Characterized by disorganized thinking, hallucinations (often visual), slowing. misperceptions (eg, illusions), disturbance Treatment: identification and management of in sleep-wake cycle, cognitive dysfunction, agitation. Reversible. underlying condition. Orientation protocols (eg, keeping a clock or calendar nearby), Usually 2\u00b0 to other identifiable illness (eg, CNS \u0090\u00a0sleep disturbances, and \u008f\u00a0cognitive disease, infection, trauma, substance use\/ stimulation to manage symptoms. withdrawal, metabolic\/electrolyte disturbances, Antipsychotics (eg, haloperidol) as needed. hemorrhage, urinary\/fecal retention), or Avoid unnecessary restraints and drugs that medications (eg, anticholinergics), especially may worsen delirium (eg, anticholinergics, in older adults. benzodiazepines, opioids). Most common presentation of altered mental status in inpatient setting, especially in the ICU or during prolonged hospital stays. uploaded by medbooksvn","578 SECTION III Psychiatry\u2003 \uf07d\u2009Psychiatry\u2014Pathology Psychosis Distorted perception of reality characterized by delusions, hallucinations, and\/or disorganized thought\/speech. Can occur in patients with psychiatric illness or another medical condition, or Delusions secondary to substance or medication use. Disorganized thought False, fixed, idiosyncratic beliefs that persist despite evidence to the contrary and are not typical Hallucinations of a patient\u2019s culture or religion (eg, a patient who believes that others are reading his thoughts). Types include erotomanic, grandiose, jealous, persecutory, somatic, mixed, and unspecified. Speech may be incoherent (\u201cword salad\u201d), tangential, or derailed (\u201cloose associations\u201d). Perceptions in the absence of external stimuli (eg, seeing a light that is not actually present). Contrast with misperceptions (eg, illusions) of real external stimuli. Types include: \u0083\t Auditory\u2014more commonly due to psychiatric illness (eg, schizophrenia) than neurologic disease. \u0083\t Visual\u2014more commonly due to neurologic disease (eg, dementia), delirium, or drug intoxication than psychiatric illness. \u0083\t Tactile\u2014common in alcohol withdrawal and stimulant use (eg, \u201ccocaine crawlies,\u201d a type of delusional parasitosis). \u0083\t Olfactory\u2014often occur as an aura of temporal lobe epilepsy (eg, burning rubber) and in brain tumors. \u0083\t Gustatory\u2014rare, but seen in epilepsy. \u0083\t Hypnagogic\u2014occurs while going to sleep. Sometimes seen in narcolepsy. \u0083\t Hypnopompic\u2014occurs while waking from sleep (\u201cget pomped up in the morning\u201d). Sometimes seen in narcolepsy. Contrast with illusions, which are misperceptions of real external stimuli (eg, mistaking a shadow for a black cat). Mood disorder Characterized by an abnormal range of moods or internal emotional states and loss of control over them. Severity of moods causes distress and impairment in social and occupational functioning. Mania Includes major depressive, bipolar, dysthymic, and cyclothymic disorders. Episodic superimposed psychotic features (delusions, hallucinations, disorganized speech\/behavior) may be present at any time during mood episodes (other than hypomania). MDE MDE with psychotic Bipolar I Bipolar II Schizoa ective disorder features Hypomania Euthymia Dysthymia Depression Psychotic features Psychosis only occurs Requires 1 episode of mania. Requires 1 episode of Psychosis overlaps with mood episodes with mood episodes Psychotic features possible hypomania and 1 MDE. but must occur by itself for > 2 weeks during manic or depressive Psychotic features possible Mania\/hypomania during MDE, but does not episodes. occur with hypomania Euthymia Major depressive episode (MDE)","Psychiatry\u2003 \uf07d\u2009Psychiatry\u2014Pathology SECTION III 579 Schizophrenia spectrum disorders Schizophrenia Chronic illness causing profound functional Associated with altered dopaminergic activity, impairment. Symptom categories include: \u008f\u00a0serotonergic activity, and \u0090\u00a0dendritic \u0083\t Positive\u2014excessive or distorted functioning branching. Ventriculomegaly on brain (eg, hallucinations, delusions, unusual imaging. Lifetime prevalence\u20141.5% (males thought processes, disorganized speech, >\u00a0females). Presents earlier in males (late teens bizarre behavior) to early 20s) than in females (late 20s to early \u0083\t Negative\u2014diminished functioning (eg, flat 30s). \u008f\u00a0suicide risk. or blunted affect, apathy, anhedonia, alogia, social withdrawal) Heavy cannabis use in adolescence is associated \u0083\t Cognitive\u2014reduced ability to understand or with \u008f\u00a0incidence and worsened course of make plans, diminished working memory, psychotic, mood, and anxiety disorders. inattention Treatment: atypical antipsychotics (eg, Diagnosis requires \u2265 2 of the following active risperidone) are first line. symptoms, including \u2265 1 from symptoms #1\u20133: 1.\tDelusions Negative symptoms often persist after treatment, 2.\t Hallucinations, often auditory despite resolution of positive symptoms. 3.\t Disorganized speech 4.\t Disorganized or catatonic behavior 5.\t Negative symptoms Symptom onset \u2265 6 months prior to diagnosis; requires \u2265 1 month of active symptoms over the past 6 months. Brief psychotic disorder\u2014\u2265 1 positive symptom(s) lasting between 1 day and 1 month, usually stress-related. Schizoaffective Schizophreniform disorder\u2014\u2265 2 symptoms lasting 1\u20136 months. disorder Shares symptoms with both schizophrenia and mood disorders (MDD or bipolar disorder). To Delusional disorder differentiate from a mood disorder with psychotic features, patient must have \u2265 2 weeks of psychotic symptoms without a manic or depressive episode. Schizotypal personality disorder \u2265 1 delusion(s) lasting > 1 month, but without a mood disorder or other psychotic symptoms. Daily functioning, including socialization, may be impacted by the pathological, fixed belief but is otherwise unaffected. Can be shared by individuals in close relationships (folie \u00e0 deux). Cluster A personality disorder that also falls on the schizophrenia spectrum. May include brief psychotic episodes (eg, delusions) that are less frequent and severe than in schizophrenia. Manic episode Distinct period of abnormally and persistently elevated, expansive, or irritable mood and \u008f\u00a0activity or energy. Diagnosis requires marked functional impairment with \u2265 3 of the following for \u2265 1 week, or any duration if hospitalization is required (people with mania DIG FAST): \u0083\t Distractibility \u0083\t Flight of ideas\u2014racing thoughts \u0083\t Impulsivity\/Indiscretion\u2014seeks pleasure \u0083\t \u008f goal-directed Activity\/psychomotor without regard to consequences (hedonistic) Agitation \u0083\t Grandiosity\u2014inflated self-esteem \u0083\t \u0090 need for Sleep \u0083\t Talkativeness or pressured speech uploaded by medbooksvn"]
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