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CM-Neuro Exam 4 Review Lecture 22-CNS Tumors CNS tumors accounts for 2% of all cancers. Most common malignant tumor is a GBM (glioblastoma) Most common benign tumor is a meningioma 25% are asymptomatic Adults-33% malignant Children-65% malignant, leading cause of death, 2nd most common tumor Male>female; Caucasian>blacks Pathogenesis Sequential accumulation of genetic aberrations, loss of chromosomes 1p and 19q. Defects in PTEN, Rb, p53, and cell-cycle pathways. Tumors graded I-IV, higher grade worse the tumor. Astrocytomas (which aren’t that bad) can become secondary glioblastomas. Risk Factors for Developing: Exposure to ionizing radiation Family history Genetic syndromes-neurofibromatosis, tuberous sclerosis, von Hippel-Lindau, etc. 5 yr mortality rates: Anaplastic astrocytoma-30% GBM-3% <14 yrs-62% >65 yrs-5% Diagnosis MRI w/gadolinium is the gold standard due to high sensistivity CT w/contrast is ok for pt unable to complete MRI. Clinical Presentation Headache-waking from sleep Seizures Focal neuro deficit Confusion Memory loss Personality changes N/V Herniation Syndromes: Uncal herniation (1)-temporal lobe lesion protrudes through tentorial notch o Structures impinged are PCA, contralateral peduncle and midbrain o Neuro findings-unilateral dilated pupil from ipsilateral CNIII compression, oculomotor plasy, homonymous hemianopia (visual loss with respect to vertical midline), and contralateral hemiparesis Central herniation (2)-midline tumor compresses basal ganglia, thalamus and midbrain. o Neuro findings-small pupils, lethargy, and Cheyne-Stokes respirations Cingulate herniation (3)-medial frontal lobe tissue is pushed under falx cerebri anteriorly. o Critical brian structures not typically involved early on. o Hernia syndrome is often an asymptomatic precursor to the other syndromes. Transcalvarial herniation (4)-also called ‘external herniation.’ o Can be caused by brain edema, pushing outward through fractured skull or craniotomy. o May prevent closure from taking place. Upward herniation (5)-also called upward cerebellar herniation. o One of the two posterior fossa herniations. o Cerebellar signs and some midbrain effects. Tonsillar herniation (6)-posterior fossa tumor compresses downward into foramen magnum, also called Chiari Malformation. o Neuro findings-posterior headache, cough, induced syncope, vomiting, respiratory changes. o Lhermittes Sign-dyesthesias in the arms and legs with bending neck forward. EM management-neuro/neurosurg consult, intubate and hyperventilate, IV mannitol, dexamethasone, and ICU care. o Seizures-stabilize the environment, use anticonvulsants, and imaging (MRI w/gadolinium). o DVT-duplex US to diagnose in extremities, CT angiography to dx in lung. Anticoagulation therapy (heparin and lovenox). Adult Tumors Gliomas-loss of heterozygosity for 1p and 19q indicates likelihood of response. Methylation of MGMT promoter results in better prognosis o Glioblastomas (60-70%) Most common primary brain tumor, medial survival <1 yr. Incidence rising in older population XRT and temozolamide better than XRT alone. Highly vascularized with elevated VEGF expression. Bevacizumab targets VEGF, and can improve outcomes when combined with chemo. o Anaplastic astrocytoma (10-15%) o Anaplastic oligodendroglioma/anaplastic oligoastrocytoma (10%) o Anaplastic ependymomas/gangliomas-few 5% of all CNS malignancies RT is commonly administered, no standard chemo Recurrence has poor outcome o Grade III and IV Meningiomas o 20-25% of all CNS tumors. o MRI shows: convexities, parasellar, ‘dural tail’ o Surgery if symptomatic o Stereotactic radiosurgery for <3 cm Germ Cell Tumors o Germinoma o Embryonal carcinoma o Choriocarcinoma o Teratoma CNS lymphoma-rare o Risk factors include immunosuppression. o Prognosis better if: Age <60 Good performance status Not associated with HIV Disease limited to cerebellum o Treatment Chemo-high dose methotrexate Radiation Intrathecal chemo HIV management w/HAART Pituitary adenomas: 10-25% of CNS tumors, either benign, invasive, or carcinoma. Most are adenomas. Most are asymptomatic. o Prolactinoma-pituitary tumor that produces prolactin. Symptoms: headache, visual field deficits, oligomenorrhea or amenorrhea, reduced fertility, loss of libido, ED, and galactorrhea. o Coricotroph-ACTH secreting tumor Symptoms: headache, visual field deficits, proximal myopathy, centripetal fat distribution, neuropsych symptoms, striae (irregular areas of skin that look like bands), ability to easily bruise/skin thinning, hirsutism, and osteopenia. o Somatotroph-Growth hormone secreting tumor Symptoms: headache, visual field deficits, growth of hands and feet, coarsening of facial features, carpal tunnel syndrome, snoring and obstructive sleep apnea, jaw growth and prognathism, osteoarthritis and arthralgia, and excessive sweating. o Thyrotroph-TSH secreting tumor Symptoms: palpitations, tremor, weight loss, insomnia, hyperdefecation, and sweating. o Non-functioning tumors (endocrine inactive tumor) Symptoms: headache, visual field deficits, pituitary insufficiency due to compression of pituitary stalk or destruction of pituitary tissue by tumor. Rarely ovarian overstimulation, testicular enlargement, or increased testosterone levels. Metastatic o Complication in 20-40% of CNS tumors o Multiple mets in 70% of pts. o Increasing incidence due to MRI imaging and longer survivals improving chemotherapy. o Solid tumors: Lung-50% Breast-15-20% Unknown primary-10-15% Melanoma-10% Colon-5% Management of CNS Tumors Surgery o Depends on age and performance status o Proximity to functional areas of the brain o Feasibility of debulking o Feasibility of complete resection o In reoccurrence, time since last resection Radiation o Ionizing radiation damages DNA, apoptosis leads to cell demise, rapidly growing cells are utilizing nucleotides at a greater rate than dormant. o Kid’s brains are very different than adults o Normal tissue tolerance is looked up in a book, brain doesn’t tolerate well. o Stereotactic radiosurgery-high dose radiation delivered to small volume w/in the brain with high precision o Gamma knife o Whole brain radiation therapy Chemotherapy o Works best when tumor burden is small, fewer cells to kill, more dividing, and less chance of resistance. o Combine active drugs making effects additive, decreases chance of resistance o Traditional agents damage DNA in dividing cells, based on dose intensity/density. Immunotherapy Vaccination therapy Intrathecal chemotherapy Lecture 23-Aphasias and Other Cortical Syndromes Broca’s Aphasia Broken Broca’s Decreased fluency, good comprehension, poor repetition and naming. Inferior frontal lobe (usually left) Contralateral weakness can be present Wernicke’s Aphasia Wordy Wernicke’s; word salad Good fluency (lots of output, but meaningless), poor comprehension (can’t follow commands), poor repetition and naming. May find homonymous hemianopsia contralateral to lesion Posterior superior temporal lobe on dominant side (usually left) Conduction Aphasia Preserved fluency and comprehension, but poor repetition and naming. No other neuro findings. Global Aphasia Trouble with all features of language: fluency, comprehension, repetition and naming. Not altered or waxing/waning as would be likely with encephalopathy. Unilateral or bilateral weakness can be present. Easy to confuse with confusion/encephalopathy Aphasia Etiology Cerebral contusion, subdural or epidural hematoma Ischemic or hemorrhagic vascular events Ictal or post-ictal deficit with focal seizures Mass lesions such as brain tumor, abscess, or toxoplasmosis Inflammatory or autoimmune disorders Developmental disorders such as language delay or autism Degenerative disorders such as Huntington’s, Alzheimer’s, etc. MCA Syndrome Contralateral hemiplegia or hemiparesis (arm>leg) Contralateral hemisensory syndrome Homonymous heminanopsia Contralateral lower facial weakness Speech or language abnormality Alexia-inability to read Letter blindness-cannot read letters but can read and comprehend familiar words. Wrenches’ may have problems with written and spoken language but can read fluently aloud. Parietal-occipital lesions-may not be associated with impaired writing. o Alexia without agraphia-cannot read but can write on dictation. o Damage to pathways conveying visual input from both hemispheres to the angular gyrus. Gerstman’s Syndrome Writing disturbance, finger agnosia, acalculia, r/l disorientation, difficulty spelling words and understanding spelled words. Pure angular gyrus lesion most likely if person doesn’t have a Wrench’s aphasia Many patients with alexia with agraphia have a partial or complete gerstman’s syndrome. Anton’s Syndrome Visual agnosagnosia-pt is blind but denies any difficulty seeing. Confabulate about what they see Secondary to acute bilateral bi-occipital lesions. Agnosognostic component may come from interruption of the thalamic connections to the right parietal association cortex or right hemispheric dysfunction. Balint’s Syndrome Bilateral parietal-occipital lesions. Failure to shift gaze on command, unable to redirect attention voluntarily Optic ataxia-failure to reach a target under visual control, appears clumsy. Decreased visual attention-affect many peripheral fields resulting in tunnel vision Visual simultanagnosia-can’t see whole picture but can name parts. Internal Carotid Occulsion-Acute Contralateral hemiplegia Contralateral sensory deficit Mutism, aphasia, or dysarthria Conjugate eye deviation toward lesion Homonymous hemianopsia opposite the lesion Horner’s syndrome (ptosis, miosis, and decreased sweating of the face on same side) ipsilateral to the lesion Contralateral lower facial weakness Cerebral edema may be life-threatening Vertebrobasilar artery syndrome Locked-in syndrome-lesions in bilateral ventral pons with sparing of the reticular activating system. Characterized by aphonia, quadriplegia, and preserved eye movement. Wakefulness maintained Lacunar Stroke Syndromes Pure motor hemiplegia o Contralateral face and arm > leg weakness o Mild dysarthria sometimes found o No vision, language, or sensory change o Lesion usually in contralateral internal capsule, posterior limb. Pure hemi-sensory deficit o Contralateral face, arm, trunk, and leg numbness, paresthesias and reduction of pain and temp sensation. o Lesion usually in contralateral ventral posterior lateral thalamic nucleus. Posterior Cerebral Artery Syndrome Contralateral homonymous hemianopsia May have no other symptoms other than visual field cut. Anterior Cerebral Artery Syndrome Contralateral hemiparesis (leg>arm) Akinetic mutism-no movement, no speech Behavioral or memory disturbance Dysarthria or transcortical motor aphasia, similar to Broca’s but repetition is intact. Conjugate eye deviation toward lesion. Lecture 24-Localization in Clinical Neurology Central Lesions Weakness/loss of movement, sensory loss, cranial nerve dysfunction, ataxia, increased tone/hyperreflexia, language dysfunction, extra movements. Peripheral Lesions Loss of reflexes, atrophy, dermatomal sensory loss, involvement of muscle group supplied by a particular nerve/nerve root, and weakness/atrophy. Spinal Cord Innervation Levels C7-Middle finger T4-nipple line T6-bottom of sternum T10-level with abdomen T12-pubic bone S3, S4 and S5-nerves in the genital area. UMN vs LMN UMN o No wasting o Increased tone o Fasciculations absent o Increased reflexes o Extensor plantar reflex LMN o Wasting o Decreased tone o +/- fasciculations o absent/decreased reflexes o flexor plantar reflex Middle Cerebral Artery LOC unusual-usually a sign of impending herniation Occlusion at stem-hemiplegia, hemianesthesia, homonymous hemianopia, language dysfunction. Contralateral eye deviation-frontal eye fields, more commonly insula and operculum Vertigo-insular involvement Visual field disturbance-large infarcts, supplies upper ½ optic radiation Neglect-impaired response to contralateral space, usually right lesion Apraxia-acquired disorders of execution Anterior choroidal artery Branch of intracranial ICA Supplies posterior 2/3 of the posterior limb of internal capsule, retrolenticular fibers posterior to the IC, posterior optic tract, medial pallidum, tail of caudate, choroid and thalamus, lateral geniculate body. Clinical findings include motor and sensory involvement, mutism, pseudobulbar state, and other visual deficits. 1-10% of all infarcts. Anterior cerebral artery Arises as medial branch of birfurcation of the ICA. Supplies the whole of the medial surfaces of the frontal and parietal lobes, and anterior 4/5 of corpus callosum. Weakness and sensory loss o Leg > arm, usually more proximal o Clumsy or slow movements out of proportion to weakness o Discriminative senses often affected o Pain, temp, gross touch less affected. Recurrent artery of Heubner o Supplies head of caudate, anterior inferior part of internal capsule anterior limb, anterior globus pallidus, uncinate fasciculus, olfactory regions, anterior putamen and hypothalamus o Contralateral weakness of face and arm w/o sensory loss, severe contralateral hemiplegia, cognitive. Posterior cerebral artery Homonymous hemianopia, quadrantanopia (vision loss in one quarter of vision), palinopsia (images persist after stimulus is gone). Repeated object in the affected field. Visual agnosia-usually alexia w/o agraphia. Difficult naming items presented visually, able to do when presented tactily or auditory. Amnesia-medial temporal lobe, can’t make new memories. May last 6 months. o Alexia without agraphia-lesion of corpus callosum o Alexia with agraphia-lesion of angular gyrus o Language dysfunction Cerebellar Infarcts Superior, anterior inferior, and posterior inferior cerebellar arteries. SCA with PICA and AICA can also be involved. Brainstem sometimes involved with SCA. SCA Syndrome o Among the most frequent. o Ipsilateral dysmetria (lack of coordination of movement, overshoot with hand), ipsilateral Horner’s, contralateral temp and pain loss, contralateral 4th nerve palsy. o Unusually choreoathetosis, bilateral hearing loss, and sleep disorders. o Rostral SCA Coma, dysmetria, ipsilateral Horner’s, contralateral pain and temp loss, and 6th nerve palsy, dysarthria, n/v. AICA Syndrome o Vertigo, n/v, tinnitus, dysarthria o Ipsilateral facial palsy, hearing and trigeminal sensory loss, contralateral pain and temp loss. PICA Syndrome o Medulla may be involved, caudal portion of PICA. Lateral medullary syndrome-contralateral ataxia, hoarseness, dysarthria, dysphagia. Visual disturbance, ipsilateral facial pain. Decreased pain/temperature contralateral o If medulla isn’t involved then vertigo, ataxia, headache, and horizontal nystagmus is present. o May present as labyrinthitis Lectures 25 & 26-Cortical Syndromes Dementia-progressive loss of intellectual function with memory loss being the central primary clinical feature. Abnormalities secondary, with language, spatial processing, praxis, and executive function. Cortical dementia-major symptoms include changes and disturbances in memory, language, perception and praxis. o Regions affected include temporal, parietal, and frontal lobes of brain cortex. o Alzheimer’s disease, diffuse lewy body disease, vascular dementia, and frtontotemporal dementia are examples. Subcortical dementia-behavior changes, emotional problems, slowing of motor function, disturbance in executive function, and less pronounced memory loss are key symptoms. o Thalamus, striatum, midbrain, and striatofrontal projections are affected regions of the brain. o Parkinson’s disease, progressive supranuclear palsy, normal pressure hydrocephalus, Huntigton’s, Creutzfeldt-Jakob and chronic meningitis are examples. Neurodegenerative dementia-involves a primary degenerative disease process with origin being in the CNS. o Most common underlying cause of dementia o Alzheimer’s disease, frontotemporal dementia and diffuse Lewy body disease are examples of this. Other causes of progressive Dementia-origin of degenerative process causing the dementing illness lies outside CNS or is of non-organic etiology o Includes structural disease or trauma, vascular disease, etc. Treatable causes of dementia Less than 10% are correctable with treatment. Structural processes, infections, metabolic disease, nutritional deficiencies and psychiatric issues must be considered to rule out reversible or treatable conditions. Underlying conditions that can be treated: pseudodementia from depression, normal-pressure hydrocephalus, thyroid hormone deficiency/excess, thiamine deficiency, tertiary syphilis, and alcoholism. Dementia Work-Up Electrolytes UA CBC w/Diff Folate and Vit B12 Liver, Renal and Thyroid fx Serologic studies for Syphilis and other studies for chronic infection LP EEG MRI and CT Neuropsychological testing o MMSE (memory and language) o Clock drawing test (visuospatial) o ‘Comb your hair’ (praxis) o Name as many animals as you can in sixty seconds (verbal fluency) Alzheimer’s Disease Complex, progressive disease that destroys cells in the brain. Terminal dementing illness that results in total care prior to death. Most common form of dementia, 5.2 million Americans. Early and late onset variants. 6th leading cause of death in US, number of people with this disease is rising. Characterized by: o Gradual memory loss and difficulties in learning. o Problems with reasoning and judgment o Loss of language skills and disorientation o Decline in ability to perform routine tasks o Changes in personality and behavior Costs a lot to care for AD and Dementia pts. Exact cause unknown, genetic research however, links chromosomes 1, 14 and 21 to early onset AD, and the ApoE4 gene on chromosome 19 has been linked to late onset AD. o Amyloid plaques and neurofibrillary tangles are important components of interest in this disease process. o Clumps of beta-amyloid fragments that accumulate between abnormal nerve cell axons and dendrites forming dense, insoluble structures o Neurofibrillary tangles are twisted paired strands of hyper-phosphorylated microtubule associated protein called ‘Tau’ that form inside brain cells results in inclusion bodies. Correlation between density of tangles and antemortem cognition. o Both plaques and tangles play a role in blocking neuron communication and disrupt vital cell processes. Ach is significantly decreased in AD. o Acetylcholine is an important neurotransmitter in areas of the brain involved in process of memory formation. Implies that this is related to cognitive impairment and disordered memory. Current pharmacotherapy targeted at inhibiting Ach breakdown. Diagnosing AD Clinical diagnosis based on comprehensive history, direct exam of mental/physical status, lab findings, neuropsych testing and neuroimaging. Can be made with 90% accuracy. The only way to absolutely confirm is a through post-mortem brain autopsy. Management of AD Nonpharmacological Behavioral Interventions o Direct behavioral intervention by caregivers o Safe structured environment o Activity therapy o Psychotherapeutic interventions o Pastoral interventions Cognitive Enhancers o Drugs that work as cholinesterase-inhibitor or glutamate antagonist. o Tacrine, Donepezil, Rivastigmine, and Galantamine are cholinesterase inhibitors o Memantine is glutamate antagonist o Benefit is modest. Medications for Behavioral Symptoms o Antispychotics o Antidepressants o Mood Stabilizers o Anxiolytics o Hypnotics o Pain medications Education and support for Caregivers o Caregiver burden counseling o Training and teaching for caregivers o Building family/social support o Respite services and care assistance o Legal services o Medical/ancillary services o Advocacy groups Long Term Care Goals o Provide AD pt with as much independence and functionality in the least restrictive setting possible. o Must be practiced with safety in mind, may have to place pt in a long term care facility, which requires prep from all involved. Modifiable strategies for use in AD o Mental stimulation o Physical activity o Social engagement o Proper nutrition o Spiritual growth Diffuse Lewy Body Disease Characteristics o May overlap with AD and PD. o Visual hallucinations o Sensitivity to antipsychotic meds o More rapid evolution of dementing process. o Lewy bodies found in brainstem, limbic system and cortex. Vascular Dementia Brain damage secondary to strokes or micro-infarcts. Neuroimaging reveals neuronal damage Focal neuro deficits are common and there is a supportive clinical time line of events Hx of HTN Vascular dementia can overlap with AD causing a mixed dementia Frontotemporal Dementia Pick’s disease is classic form of this type of dementia, which has Pick’s bodies present. Frontal and temporal lobe atrophy. May account for up to 5% of dementia. Frontal lobe syndrome manifests by inappropriate social behavior. Onset is usually earlier than other dementias, occurring during 50s. ½ of pts have a family history of similar dementia, being a link between ‘Tau’ protein mutation on chromosome 17. Parkinson’s Disease Dementia occurs in 35-55% of those with PD. Impacts executive function much more than language or visuospatial processing. Lewy bodies restricted to brainstem. Bradyphrenia and bradykinesia are present in PD. Depression also common in PD and may worsen cognitive function. Drugs that treat PD may induce psychosis or delirium, must rule out before dementia diagnosis. Normal Pressure Hydrocephalus Rare occurrence as cause of dementia, results from obstruction of flow of spinal fluid. Presents with classic triad: dementia, gait disturbance, and urinary incontinence. Other features include enlarged ventricles, and elevated ICP. Shunt placement is tx, and effective in dementia reversal. Creutzfeldt-Jakob Disease Rare occurrence as cause of dementia with a prion protein being transmissible agent. Presents with dementia, myoclonus, and abnormal EEG. Spongiform encephalopathy caused by CJD, rapidly progresses with death in <1 yr. AIDS HIV has direct action on brain. Subcortical structures affected more than cortex with bradyphrenia and bradykinesia. No disturbance of language. Forgetfulness, poor concentration and slowed thinking are common. Executive dysfunction and apathy may be more evident as dementia progresses. Antiviral agents may slow dementia progression. Head Injury Dementing illness that is more retrograde than anterograde. Degree of dementia correlates with extent of brain damage. Usually doesn’t progress unless further trauma occurs. Recovery may take years to return to baseline. Also known as Chronic Traumatic Encephalopathy, Dementia Pugilistica, or Boxer’s Dementia. Korsakoff’s Syndrome End result of untreated Wernicke’s encephalopathy caused by thiamine deficiency. Inability to establish new memory, affected pt’s often confabulate responses. Often seen with chronic alcoholism Thiamine replacement therapy mandated. Benign Forgetfulness of Aging Aging associated with mild loss of memory, difficulty recalling names and forgetfulness of dates. Poor performance and delay to recall tasks. Verbal fluency remains intact, with vocab increasing. Dementia is not the normal end-product of aging. Transient Global Amnesia Dramatic memory disturbance that affects pts older than 50 yrs. Pt typically has one episode, but more can occur Characterized by temporal and spatial disorientation with orientation for person remaining intact. Retrograde and anterograde amnesia persist for several hours. Pts very anxious/distressed asking same questions over and over. Vascular insufficiency to midbrain including hippocampus and midline thalamic projections may be underlying cause. Psychogenic Amnesia Incosistent loss of resent and remote memory exhibiting an indifference to the deficit. Pt will ask ‘Who am I?’ Disoriented to person. Also known as dissociative amnesia. Pseudodementia Dementia syndrome of depression. Found in about 5% of pts Difficult to distinguish from other causes of dementia, and can coexist with other dementia. Must r/o pseudodementia. Responds to ECT and anitdepressants. Huntington’s Disease Autosomal dominant illness on chromosome 4, CAG repeats. Onset 30-50 yrs. Causes dementia and chorea within a year of each other. Atrophy of cerebral cortex and heads of caudate nuclei. Subdural Hematoma Reversible dementia, most caused by head trauma. Sx include headache, confusion, inattention, apathy, memory loss, drowsiness and coma. Lateralizing signs are less common. Delirium Rapid onset, disorganized mental process which causes shit in attention and awareness. Disordered thinking, impaired perceptual discrimination. Can be caused by general medical condition, intoxication, withdrawal or other etiologies. Lecture 27-Altered State of Consciousness States of Consciousness Alert and awake-normal state of arousal Lethargy-fatigued with minimal difficulty maintaining alertness Stupor-moderate reduction in alertness, with decreased interest in environment. Responsive to stimuli Obtunded-unresponsivenss with arousal only with painful stimulus. Returns to unresponsive with removal of stimulus Comatose-unresponsive to noxious stimuli. Consciousness depends on an intact ascending reticular activating system and both cerebral hemispheres. Exam of comatose patient Verbal responses-oriented, confused, inappropriate, incomprehensible, none at all. Eye opening-spontaneous, verbal response, noxious response, none at all. Pupillary reactions-present or absent. o Normal pupils sugges coma not due to structural lesion of CNS o Unilateral dilation suggests structural injury. o Bilateral dilated pupils suggests severe brain injury. o Bilateral midposition pupils unresponsive to light indicates midbrain lesion. o Pinpoint pupils suggests medication effects, or lesion at pons. Corneal response-present or absent Spontaneous eye movement-orienting, roving, miscellaneous, none at all. Respiratory pattern-regular, periodic, ataxic. Motor responses-obeys, localizes, withdrawals, abnormal flexion, abnormal extension, none o Purposeful o Semi-purposeful o Random, non-purposeful o Decorticate-legs stiffly extended, arms flexed to chest or neck (toward core) o Decerebrate-legs and arms stiffly extended (away) DTRs-normal, increased, decreased Tone-normal, para, flex, ext, flaccid. GCS Eye Opening o Never-1 o Pain-2 o Verbal-3 o Spontaneous-4 Verbal Response o None-1 o Sounds-2 o Inappropriate words-3 o Disoriented-4 o Oriented-5 Motor Response o None-1 o Extensor-2 o Flexor posture-3 o Withdrawal-4 o Localization-5 o Obeys-6 Increased ICP detected by deterioration in mental status, pupils, or motor exam Coma Management: Ensure basic metabolic parameters are able to support brain function. Check blood gases, H&H, Na, K, Ca, BUN and BGL, and liver enzymes. Management of increased ICP Hyperventilation-lasts 1-2 hrs Mannitol-lasts 4-6 hrs Mannitol and Lasix are synergistic Hyperosmolality with 3% NaCl DDx of Coma: VITTAMIN D&E V-Vascular-infarctions or hemorrhage I-Infections T-Trauma T-Toxic A-Anoxic M-Metabolic-hypoxia, hypercapnia, acidosis, etc. I-Iatrogenic disorders-results from medical procedure/intervention N-Neoplasm D-Drugs-sedatives, EtOH, tranqs, etc. E-Endocrine/Epilepsy/Emotional: hypoglycemia, hyperglycemia, DKA, post-ictal state, etc. Coma Copycats Locked-in syndrome-pt alert and aware, quadriplegic with lower cranial nerve plasy. Persistent vegetative state-absent cognitive function, but retained vegetative components. Brainstem preserved. Catatonia-mute with marked decrease in motor activity, psych issue. Prognosis No 100% predictability Only 15% of trauma comas make satisfactory recovery. Functional recovery depends on cause of coma. Age not predictive of recovery Longer the coma lasts, the less likely pt is to regain function. Trauma comas do better than nontraumatic Lecture 28-Progressive Neurodegenerative Disorders Amyotrophic Lateral Sclerosis (ALS) Hallmark is progressive loss of function in both upper and lower motor neurons. Median survival is 3-5 yrs, resp failure is COD. Males>females 95% sporadic, 5% familial Death of peripheral motor neurons leads to denervation and atrophy of corresponding muscle fibers; followed by loss of fibers in lateral columns and replacement by fibrillary gliosis causing gross cord to have an abnormal firmness. Clinical Manifestations o Early-asymmetric distal weakness without sensory abnormalities, fasciculations, spasticity and wasting. o Bulbar involvement causes difficulty chewing and swallowing. o Hyperactive tendon reflexes o Ocular motility, bladder and bowel sphincters unaffected. o Later diffuse symmetrical involvement. Lab Eval o CBC and Sed Rate o CSF exam and culture o Lyme antibody titer o Chemistries including glu and calcium o Thyroid profile o ANA o B12, Folate and Vit E levels o Protein electrophoresis o Test for heavy metal toxicity Imaging o C-spine Xray to r/o structural problem o MRI of head and C-spine to r/o other lesions o Nerve conduction studies will be normal until late stages. o Electromyography testing will show fibrillations and fasciculations World Federation of Neuro Diagnostic Guidelines o Involvement of bulbar, cervical, thoracic and lumbar areas o Definite ALS-3/4 areas involved, or SOD1 mutation positive o Probable ALS-two areas involved o Possible ALS-Only one site involved and all other causes ruled out. Differential: o Structural lesions in c-spine or foramen magnum o Infections-lyme disease, tetanus, polio o Toxicities-lead, aluminum, phenytoin, strychnine o Paraproteinemias-multiple myeloma Treatment o Supportive care with splints for foot drop and wrist and fingers to assist in gripping. o CPAP to assist in ventilation o Gastrostomy for decreased gag reflex o Speech synthesizers to help with communication. Meds-riluzole shows modest improvement Multiple sclerosis Characterized by inflammation, demyelination and gliosis of the CNS with sparing of the peripheral nerves. Affects 350,000 in the US. Femals > males. Onset is 20-40yo More common in higher latitudes. Migration studies shows increased risk when people move to high incident areas as children. Infection possibly HHV-6, chlamydia, or EBV Demyelination with initial sparing of axon results in conduction blocks and slowing of conduction. Clinical Manifestations o Symptoms often insidious and various depending on location of lesion. o Complete neuro exam is important, pt may show signs of dysfunction that are asymptomatic. o Symptoms can be intermittent and sometimes resolve spontaneously after an acute flare, making dx difficult to pin down. o Muscle weakness and clumsiness are common. Spasticity and hyperreflexia are frequently seen. Exercise induced spasticity of legs may result in gait disturbances. o Diploplia due to internuclear ophthalmoplegia from CN VI palsy. o Optic neuritis seen in 30% of MS pts, and presents with decreased central field of vision. Usually monocular, may have peri-orbital pain prior to vision loss. Fundoscopic exam may see optic disc swelling. o Sensory sx: pain, paresthesias, hyperesthesia. o Bladder dysfunction-frequency, urgency or incontinence. o Constipation o Sexual dysfunction o Cognitive dysfunction-impaired memory, attention and difficulty switching tasks. o Depression-may be reactive or endogenous o Fatigue-90% of pts, may be related to sleep disturbances, increased effort with ADLs or depression. Course of Disease o Relapsing/remitting MS-85% Discreet attacks o Secondary progressive MS Starts as relapsing/remitting MS then increasing deterioration and less attacks o Primary progressive MS-15% No attacks, gradually worse and worse o Progressive/relapsing MS Progressive with rare attacks Diagnostic Tests o MRI of brain and thoracic spine o CSF analysis shows elevated protein and WBCs Diagnosis Criteria o Documentation of 2 or more episodes of symptoms and 2 or more sigs that show pathology in non-contiguous white matter tracts of CNS o Symptoms must last >24 hrs and episodes separated by 1 month o Abnormal MRI, EP and CSF findings support diagnosis Treatment o Acute episodes require IV coritcosteroids for 3-5 days, then oral taper for 2 weeks. Plasmapheresis if not responsive to steroids. o Disease modifying drugs can be helpful to prevent exacerbations Interferon-immunosuppressive Glatiramer Acetate-induces suppressor T-Cells Natalizumab-mab prevents lymphocyte adhesion o Symptomatic therapy Ataxia/tremor-clonazepam Spasticity-diazepam, dantroline, cyclobenzaprine Pain-gabapentin, amitriptyline Bladder dysfunction-oxybutynin and hyoscyamine Prognosis o Difficult to estimate. Better prognosis if <2 episodes in 5 yrs. o 80% require assistance with ambulation and ADLs after 25 yrs o Mortality is related to complication of infection in a debilitated pt. Guillain-Barre Syndrome Clinical Manifestations o Rapidly progressive ascending areflexive motor paralysis. Sensory deficits are mild. o Evolves over a few days and peaks 2-3 weeks. o Fever is rare, muscle pain in neck, back and shoulders. o 30% require ventilator support o Autonomic involvement is common. o 70% of cases occur 1-3 weeks after an infection or immunization: campylobacter jejuni Mycoplasma pneumoniae CMV EBV Influenza vaccines-swine flu 1976 Etiology o Surface glycoproteins of infectious agents cross-react with gangliosides on the myelin sheath. o Activated B-cells produce antibodies that cause demyelination and conduction block in nerve. o Complement is deposited on outer surface of myelin sheath and leads to degradation. Evaluation o Elevated CSF protein, w/o elevated WBCs o EMG shows axonal-reduced amplitude of action potentials, conduction slowing due to demyelination. Diagnostic Criteria o Required: Progressive weakness of 2 or more limbs Areflexia Disease course less than 4 weeks Exclusion of other causes o Supportive Symmetric weakness Mild sensory involvement Absence of fever Typical CSF EMG evidence of demyelination Treatment o Initiate IV immunoglobulin G or plasmapheresis ASAP for 5 days. o Supportive care includes ventilator support, heart arrhythmias, BP, nutrition, frequent turning, DVT prophylaxis Prognosis o 85% have full recovery in several months to a year o 5-10% can have relapse o <5% mortality, death usually related to pulmonary complications and infection. Myasthenia Gravis NM disorder causing weakness in skeletal muscle. Autoimmune attack on NM junction causes a decrease in Ach receptors. Pathophysiology o Reduction and flattending of AChR sites at the postsynaptic membrane, prevents propagation of AP. Clinical features o Females (20-30yrs)>males (50-60yrs) o Characteristic patter on muscle weakness and fatigability. o Weakness of CN muscles early in disease, worse after repetitive use and better after rest. o Weakness of eyelids and extraocular muscles causes ptsosis and diplopia o Weakness with prolonged chewing o Weakness in tongue and palate causing nasal/mushy speech. o Dysphagia can cause aspiration o If intercostal or diaphragm are affected then pt is in trouble Diagnosis/Eval o Neuro exam shows weakness with repetitive tasks o Normal DTR’s o Normal sensation o Normal CT or MRI of brain o Antibodies to AChR and MuSK o Repetitive nerve stimulation will show decreased potentials and the fatigue of muscle fibers. o Anticholinesterase testing-edrophonium (muscle weakness improves) and neostigmine Treatment o Anticholinesterase medications o Thymectomy o Immunosupressive therapy o Plasmapheresis o IV Immunoglobulin o Avoid these durgs: aminoglycosides, quinolones, macrolides, nondepolarizing muscle relaxants, beta-blockers, botox, quinine, magnesium, and penicillamine Prognosis o Most pts live full productive lives. o Active phase-peak symptoms with fluctuations for 2-3 yrs o Stable phase-may worsen with infection or med changes. o May have a remission phase, with or without meds. Lecture 30-New Onset Seizures in Peds Status Epilepticus-continuous seizure activity without regaining consciousness lasting >30 minutes (historical); >5 minutes (real life). Convulsive SE Nonconvulsive SE Refractory SE-failed to respond to therapy and lasts >60 minutes Febrile SE-seizure lasting >30 minutes plus occurs between 6-60 months old, temp >38 degrees C, no CNS or metabolic cause, absence of prior non-febrile seizures. Etiology of Seizure GRAND MALS G-Glucose R-Rising BP A-Alcohol/anatomic N-Neoplasm/neuro infection D-Drugs M-Metabolic A-Arterial Disease L-Electrolytes S-Subdural/SAH Partial Seizures-focal seizure only involves part of the brain. Simple Partial-only seizure in which level of consciousness is not altered or lost. o Seizures caused by abnormal activation of a limited number of neurons, signs and symptoms that allow localization of epileptic focus. o Short 10-20 sec o Child is conscious and able to verbalize o Aware and able to remember seizure o Treat with anti-epileptics, resolves in adolescence. Complex Partial o Frequently starts with aura followed by an alteration in consciousness, then stereotypic behavior or vocalizations. o Automatisms can continue in postictal phase. o Child not always aware of seizure, and won’t remember episode. o Treat with AEDs. Partial w/ Secondary Generalization o Partial seizure generalizes secondarily if epileptic activity propagates to entire brain. Generalized Seizures-involves whole brain, caused by global activation of neurons and always impairs consciousness. Motor changes and EEG abnormalities observed bilaterally in a synchronous, symmetric pattern. Absence o Formerly referred to as petit mal seizures. o Characterized by frequent, abrupt loss of consciousness accompanied by eyelid flickering that ends abruptly with resumption of activity. o Never have an aura or postictal period. o Can be induced by hyperventilation or photic stimulation o Typical vs. atypical types. Typical: abrupt onset, eye flickering, short duration, idiopathic generalized epilepsy. 3 cycles of 3 Hz per second. Atypical: gradual onset, other prominent symptoms including aura and automation, long duration (several minutes), and focal pathology or symptomatic epilepsy. Myoclonic o Brief contractions (non-rhythmic) of a muscle, muscle group, or several muscle groups. o Action, noise, startle, photic stimulation, or percussion can sometimes provoke the seizure. Clonic o Jerking (rhythmic), that is asymmetric and irregular. o Occur more frequently in neonates, infants or young children. Tonic o Sustained muscle contraction without clonic phase. o Occur at any age and are associated with diffuse cerebral damage, often seen in kids with Lennox-Gastaut syndrome. Tonic-Clonic-grand mal seizure o Characterized by three successive phases: o Tonic phase-lasts 10-30 seconds, contractures. o Clonic phase-lasts 30-60 seconds, rhythmic jerking. o Postictal phase-lasts 2-30 minutes, state of confusion and fatigue. Atonic o Characterized by loss of muscle tone, ‘drop attacks.’ o May involve only the tone of head and neck. These kids wear helmets. Pediatric Seizure Syndromes Benign Rolandic Seizures (Benign epilepsy of childhood) o Onset age 5-10 yrs. o Infrequent self-limited seizures involving a facial or arm motor seizure; throat tingling is characteristic. o Child is conscious but cannot speak. o Occur at night while child is asleep o Can be associated with migraines. o Dominant trait, look for family history o Often left untreated. o Spontaneous remission by adolescence is typical. o BECTS-Benign childhood epilepsy with centrotemporal spikes Juvenile myoclonic epilepsy (Janz Syndrome) o Onset is 12-16 yrs. o Myoclonic jerks upon awakening that diminish through day. o Most children develop tonic-clonic seizures. o Linked to defects on chromosome 6P (AD) o Treatment with valproic acid o Excellent prognosis but lifelong treatment is required. Temporal Lobe epilepsy (TLE) o Onset in late childhood and adolescence o Typical seizure is partial complex seizure with secondary generalization o MRI may show low grade tumor, cortical malformation or mesial temporal sclerosis o Treatment with AEDs and sometimes surgery Acquired Epileptic Aphasia (Landau-Kleffner Syndrome) o Onset at 3-6yrs o Characterized by abrupt loss of previously acquired language in children. o Cortical auditory deficit. o Some pts develop generalized seizure. o Etiology is unknown. o Treatment with AEDs, steroids, and surgery. Lennox-Gastaut Syndrome (LGS) o Onset at 3-10 yrs o Mix of seizures including myotonic, tonic-clonic, atonic, absence and partical. o Treat with valproic acid, and other AEDs o Prognosis is poor, most children have Mental Retardation and behavioral problems. Infantile Spasms (West Syndrome) o Onset in infants, from 4-6 months. o Sudden flexion or extension of neck, back and extremities. o Occur in clusters lasting 10-30 sec o Occur when infant is waking up or going to sleep. o Loss of developmental milestones after onset of seizures. o Seizure type may change with age. o Associated with tuberous sclerosis o First line of treatment is with ACTH. o Prognosis based on amount of developmental delay. Diagnostics First Tier o Seizure semiology (H&P) o Interictal EEG o Video-EEG o MRI Second Tier o Invasive EEG (subdural electrodes)-electrical map o Single Photon Emission CT (SPECT)-blood flow map o Magnetoenceophalography (MEG)-functional map o PET-metabolic map Treatment Antiepileptic drugs (AEDS) Steroids: ACTH (West syndrome) and prednisone (Landau-Kleffner syndrome) IVIG Ketogenic Diet o Initial period of fasting, followed by a diet with 3:1 or 4:1, fat:nonfat ratio o Mechanism unknown o Ketosis elvates levels of beta-hydroxybutyrate and acetoacetate. Higher levels=better seizure control. o Continued for 2 yrs in children who have good sz control. o Responders can dramatically decrease or discontinue anticonvulsants. o Contraindicated with carnitine deficiency. o Metabolic work-up may be needed before starting diet. o May not be tolerated due to lack of palatability o Valproic acid can’t be used with diet. o Atkins and low-glycemic index diets are easier to start Epilepsy Surgery o Vagal nerve stimulator Used for intractable epilepsies and for seizures of diffuse or multifocal anatomic origin that cannot be resected. Electrical signals applied to left vagus nerve. Side effects: cough/voice change o Focal resection Resect epileptogenic zone o Hemispherectomy Used for diffuse hemispheric lesions o Multiple subpial transection Connections of epileptic focus are partially cut without resection. o Corpus callostomy Used for drop attacks Counseling o Education about disease o Not required to report epileptic pt to DMV o Seizure-free period of 6 months is required before driving is allowed. o Swimming in rivers, lakes or sea and underwater diving are prohibited, pools are okay o Pt with epilepsy should remain under constant supervision when swimming Lecture 31-Seizure and Epilepsy in Adults Mechanisms of Seizure Excitation-too much, neurotransmitter glutamate and aspartate. o Ionic-inward Na and Ca currents. Inhibition-too little o Neurotransmitter-GABA o Ionic-inward Cl and outward K currents Absence vs. Complex Partial Seizures Absence: o Symptoms of generalized epilepsy. o Last only seconds, can occur 100 times or more per day o Start and end abruptly, no postictal confusion o Produce little or no abnormal motor activity o Misdiagnosed as daydreaming or inattention o EEG shows 3 Hz spike and wave bilaterally Complex Partial Seizures o Symptoms of focal epilepsy o Lasts more than a minute o Cause alterations in consciousness o Followed by postictal confusion o Most frequently originate in temporal lobe and involve limbic structures o EEG shows focal spikes and sharp waves unilaterally Jacksonian March Simple partial seizures, motor signs begin with clonic or tonic movements of a discrete body part. Muscles of face and hands often involved Seizure begins in primary motor cortex and spreads to involve rest of precentral gyrus, clonic movements progress in orderly sequence (Jacksonian march) that reflects the motor cortex homunculus representation: o Thumb to fingers to face to leg. Tonic Clonic Seizure Tonic phase-occurs abruptly, inclues limb extension bilaterally. Air is ejected forcefully against tightend vocal cords, responsible for ‘epileptic cry’ Clonic phase-synchronous muscle contraction Seizure is a symptom and epilepsy is a syndrome, disease or disorder. Classification of Epilepsy Localization-related (focal, local and partial) epileptic syndrome o Idiopathic-age-related onset Benign childhood epilepsy with centrotemporal spikes (rolandic epilepsy) Childhood epilepsy with occipital paroxysms o Symptomatic Chronic progressive epilepsia partialis continua of childhood. Frontal lobe epilepsies Occipital lobe epilepsies Parietal lobe epilepsies Syndromes characterized by specific modes of precipitation Temporal lobe epilepsies o Cryptogenic-symptomatic with unknown etiology Generalized epileptic syndrome o Benign familial neonatal convulsions o Benign myoclonic epilepsy of infancy o Juvenile myoclonic epilepsy o Epilepsy with generalized tonic-clonic seizures on awakening o Epilepsy with generalized tonic-clonic seizures only o Absence syndromes o Lennox-Gastaut syndrome o Progressive myoclonic epilepsies o West Syndrome Undetermined as to whether focal or generalized Special syndromes Antiepileptic drugs Mechanism o Na inactivation-phenytoin, carbamazepine, lamotrigine, topiramate, valproic acid o GABA activation-gabapentin, topiramate, phenobarbital, valproic acid, benzos o Ca inactivation-ethosuximide Many AEDs involved in P450 system and cause significant drug interaction. o P450 inducers: barbiturates, phenytoin, carbamazepine o P450 inhibitors: Depakote is a weak inhibitor Eval of First Seizure H&P Blood tests: CBC, electrolytes, glucose, calcium, magnesium, phosphate, hepatic and renal function (LFTs, BUN, Creatinine) LP if meningitis or encephalitis suspected Blood or urine screen for drugs EEG CT or MRI of brain Seizure Precipitants Metabolic and electrolyte imbalance Stimulant/other proconvulsant intoxication Sedative or EtOH withdrawal Sleep deprivation Antiepileptic medication reduction or inadequate AED treatment Hormonal variations Stress Fever or systemic infection Concussion and/or closed head injury. Seizure Risk Factors Family history Hx of febrile seizures Hx of head trauma Hx of meningitis Hx of stroke Causes of Breakthrough Seizures (while on AEDs) Metabolic and electrolyte imbalance Stimulant/other proconvulsant intox Sedative or ethanol withdrawal Sleep deprivation AED reduction or inadequate tx Hormonal vairiations Stress Fever or systemic infection Concussion and/or closed head injury Status Epilepticus-seizures that last for 5-20 minutes Mortality is 3-20% Treatment plan: o Lorazepam first 1-2 min o Immediately followed by phenytoin or fosphenytoin o After 20 min seizure continues, add additional phenytoin or fosphenytoin o After 30 min…add phenobarbital o After 50 min…increase phenobarbital o After 60 min…anesthesia with midazolam or propofol Neuro emergency, pt’s who have first episode of status epilepticus are at risk for future episodes. Outcome is usually worse the longer the episode lasts. 12-30% of pts with a new diagnosis of epilepsy first present in status epilepticus Pseudoseizures Represents 15-30% of seizures diagnosed. Common symptom of conversion or somatization disorder. May occur in individual who has epileptic seizures. Occurs without accompanying changes in EEG. Diagnosis made by recording typical events with video EEG. Post-ictal confusion may be absent. Evidence of loss of motor control during seizure. Maintain high degree of suspicion when seizures are refractory to therapy, or when atypical features are present. Lecture 32-Ethical Decisions in Neuro Palliative vs. Hospice Care Palliative: o Addresses goals of care and focuses on quality of life, family support and symptoms management o Can begin with onset of symptoms from a serious, life-limiting disease Hospice o Specific type of palliative care provided when pt is terminally ill. o Provide team based support services to pt, family and caregivers in home or an institution. Principles of Palliative Care Respect goals, likes and choices of the dying Looks after the medical, emotional, social and spiritual needs of the dying Supports the needs of family members Helps gain access to needed health care providers and appropriate care settings Builds way to provide excellent care at the end of life. Palliative care pts live longer, because they are getting the care they need! Hospice team: Family member is primary caregiver Interdisciplinary team: o Patient’s personal physician o Hospice physician/medical director o Nurses o Home health aides o Social workers o Clergy and bereavement counselors o Volunteers Levels of Care Routine home care-most common type of hospice service, may be in private home, assisted living facility or long-term care facility General inpatient hospital care-uncontrolled distressing physical symptoms, psychosocial problems, provided in a variety of settings. Continuous home care-pt’s qualify for inpatient care but desire to remain in home. Care provided 8-24 hrs per day by LPN or RN. Dementia Affects 10% of population by age 65 Affects 50% of population by age 85 Hospitalized pts with dementia have a 6x higher mortality rate than those w/o dementia. o Contributing factors: immobility, loss of ability for self care, anhedoniapleasure from activities or hobbies is loss, decline in coordinated tasks (gait, continence and swallowing). PEG tubes are not supported in response to dysphagia and aspiration risk. Some studies indicate higher aspiration risks and higher mortality rates in pts with feeding tubes, compared to those without. Other studies suggest that enteral feeding does little to improve nutritional status or pressure ulcer rates. Benefits of not placing PEG tube: focus on other needs of pt (frequent oral care, intimacy of hand feeding for family, pleasure foods-ice cream). o Less choking on oral secretions o Fewer diaper changes o Less skin breakdown Making Medical Decisions: Capacity determined by primary physician. Doesn’t require legal or psychiatric expertise. Competence is a judicial determinance. Required when assessing a pt’s global decision making capacity for non-medical issues. Pts have the right to refuse life-sustaining medical treatments. Based on philosophical concept of respect for pt autonomy. Pts without decisional capacity have same rights as mentally competent pts. Treatment should conform to what pt would want on basis of written or oral advanced care planning. If pt’s beliefs are unknown should be based on known values, and previous choices. If all else fails make a decision in best interest of pt. Advanced care planning: pt develop and indicate preferences for care and choose a surrogate to act on their behalf. o Should be discussed regularly before acute event occurs. If you don’t agree offer empathy, and thoughtful exploration of all possibilities. o If it violates your professional integrity, refer to another physician but don’t abandon pt. Ethics consultation may be an option. Physician Assisted Suicide Oregon is only state legal, provide pt with a prescription of a drug that a known overdose will occur if taken too much of. o Must be an adult and legal resident of Oregon o Diagnosed with terminal illness, life expectancy less than six months o Make two oral requests to PCP separated by 15 days o Provide written request to physician, signed in presence of two witnesses. o Prescribing physician and consulting physician must confirm diagnosis and prognosis and determine whether pt is capable of making decision. o Prescribing physician must inform pt of alternatives o Prescribing physician must request pt to inform next of kin. Highly controversial, under this law not considered suicide. Prohibits euthanasia. Telling the Pt the Truth Code of ethics requires honesty to pt, regardless of family request. Must respect pt, their autonomy!