CNS Embryology & Development PDF

CNS CNS embryology & dev'p general embryology (what happens ) ♢ 1st wk, 2nd wk, 3rd wk germ layer derivatives ♢ ectoderm ¤ surface ectoderm ¤ neural tube ¤ neuralcrest cell ( MAPESS) Melanocytes, Adrenal med...

CNS CNS embryology & dev'p general embryology (what happens ) ♢ 1st wk, 2nd wk, 3rd wk germ layer derivatives ♢ ectoderm ¤ surface ectoderm ¤ neural tube ¤ neuralcrest cell ( MAPESS) Melanocytes, Adrenal medulla, PNS, Entrochromaffin cell,Schwann cells, Skull bone ♢ mesoderm ¤ paraxial mesoderm ¤ intermediete mesoderm ¤ lateral mesoderm ♢ endoderm regionalization of neural tube and what do they give rise to ♢ prosencephalon ¤ telencephalon ¤ diencephalon ♢ mesencephalon ♢ rhombencephalon ¤ metencephalon ¤ myeloncephalon neural tube malformations ♢ neural tube closure is complete by 5-6 weeks gestation. ♢ risk factors ¤ folate deficiency ¤ type 1 DM ¤ prior pregnancy with neural tube defect ¤ medications 1  CNS antiepileptic (valproic acid, carbamezapine ) methotrexate ♢ prevention ¤ all women should begin folic acid supplementation at least 1 month before conception ¤ average-risk patients require 0.4 mg daily ¤ high-risk patients (eg, prior affected pregnancy, antiepileptic use) require 4 mg daily. ♢ types ¤ anencephaly associated with polyhydramnios due to impared swallowing ¤ encephalocele ¤ spinabifida 1.spinabifida occulta/ closed spinal dysraphism ♧ classic manifestations ▪ lumbosacral dermatologic findings dimple hair tuft lipoma hemangioma ▪ lower exterimity neurologic deficits weakness, hypotonia, hyporeflexia ▪ bladder dysfunction, bowel dysfunction urinary incontinence recurrent urinary tract infections chronic constipation ♧ pt maybe asymptomatic for years before onset of symptoms ♧ approach to bladder dysfunction in children 2  CNS 2.meningocele 3.meningomyelocele 4.myeloschisis/ rachischisis ♢ diagnosing neural tube defects in utero ( 2nd TM ) ¤ u/s ¤ maternal serum AFP other causes of elevated AFP incorrect dating ( most common cause ) multiple gestation abdominal wall defects (gastrochisis, omphalocele) ¤ amniotic acetylcholinesterase ( AchE ) 3  CNS brain malformations ♢ holoprosencephaly ♢ lissencephaly posterior fossa malformation ♢ chiari malformations and their presentation ¤ type 1 downward displacement of the cerebellar tonsils through foramen magnum highly associated with syringomelia when and how does it manifest adolesence/ early adulthood cough headache, cerebellar dysfunction, CN dysfunctions ¤ type 2 dowmward displacement of cerebellar tonsils and vermis highly associated with myelomeningocele when and how does it manifest infancy hydrocephalus ♢ dandy walker malformation ¤ hypoplasia/ agenesis of cerebellar vermis microcephaly 4  CNS macrocephaly ♢ HC >97th percentile for age and sex ♢ causes ¤ benign familial macrocephaly due to megaloencephaly (increased brain parenchyma volume) ▪ Examination findings that are reassuring for benign macrocephaly normal development no syndromic features no signs of increased intracranial pressure (eg, bulging fontanelle) no signs of infection (eg, fever, lethargy) ¤ hydrocephalus cerebral palsy 5  CNS is a nonprogressive motor dysfunction due to neurologic injury causes ♢ prematurity/ LBW ( most common cause ) ♢ intrauterine infection ♢ perinatal stroke ♢ hypoxic ischemic injury ♢ Etiology is often multifactorial & the underlying cause may not be identified. presentation ♢ motor delay ♢ early hand preference ♢ persistent neonatal reflexes ♢ abnormal tone ( Infants with CP may initially be hypotonic, but spasticity develops with time. Increased tone is accompanied by hyperreflexia and often clonus. diagnosis ♢ Clinical (usually by age 1-2) ¤ abnormal motor development & tone (eg, spastic, dyskinetic, ataxic) ♢ MRI of the head ¤ imaging findings of d/n causes of CP ▪ prematurity/ LBW periventricular leukomalacia Intraventricular hemorrhage ▪ intrauterine infection calcifications (eg, cytomegalovirus, toxoplasmosis ▪ perinatal stroke vascular distribution ▪ hypoxic ischemic injury Watershed injury mngt ♢ physical, occupational, speech therapies ♢ nutritional support ♢ antispastic medications prognosis ♢ Permanent, nonprogressive deficits comorbidities ♢ Epilepsy ♢ Speech disorders (eg, aphasia, dysarthria) ♢ Intellectual disability ♢ Feeding difficulties & poor growth ♢ Respiratory (eg, aspiration, restrictive lung disease) ♢ Vision/hearing impairment 6  CNS ANATOMY Brain cerebrum ♢ cortex ¤ lobes 1. frontal 2. temporal 3. parietal 4. Occipital 5. Insula ¤ surfaces and major sulci and gyri lateral medial inferior orbital tentorial ¤ major functional areas ( motor, sensory, association ) motor areas 1. Primary motor cortex 2. Premotor cortex 3. supplementary motor area 4. frontal eye field 5. broca's area sensory and association areas 1. primary somatosensory area 2. somatosensory association area 3. supramarginal gyri 4. angular gyri gerstmann's syndrome 5. wernicke's area ♤ types of aphasia ( comperhension, fluency, repitition ) broca's aphasia/ experessive aphasia/ nonfluent aphasia wernicke's aphasia/ receptive aphasia/ fluent aphasia conductive aphasia global aphasia (broca+wernicke+arcuate fasciculus) TMA caused by brain damage that results in the separation of language centers from other cortical areas involved in speech production/comprehension 7  CNS 6. primary auditory area 7. auditory association area 8. gustatory area 9. olfactory area 10. primary visual cortex 11. visual association area ♢ lateral ventricles ♢ white matter ¤ commissural fibers ( what do they connect ) corpus callosum ( rgbs ) anterior commissure posterior commissure habenular commissure hippocampal commissure/ fornix ¤ association fibers ( what do they connect ) arcuate fasciculus uncinate fasciculus superior longitudinal fasciculus inferior longitudinal fasciculus ¤ projection fibers corona radiata internal capsule ♢ basal ganglia ( video downloaded ) ¤ caudate nucleus ¤ lentiform nucleus putamen globus pallidus ¤ claustrum diencephalon ( video ) ♢ thalamus 8  CNS ¤ thalamic nuclei and their function anterior nuclei medial nuclei MGB LGB ventrolateral nuclei VPM nuclei VPL nuclei ♢ hypothalamus ¤ hypothalamic nuclie and their function anterior posterior ventro medial lateral paraventricular & supraoptic preoptic suprachiasmatic 9  CNS ♢ epithalamus ♢ subthalamus brainstem ♢ midbrain cerebral aqueduct cereberal peduncles tectum ( superior and inferior colliculi ) ♢ pons ♢ medulla cerebellum 10  CNS ♢ vermis ( spinocerebellum ) ♢ lateral zones ( cerebro cerebellum ) ♢ flocculonodular lobe ( vestibulocerebellum ) ♢ nuclei dentate, emboliform, globose , fastigi ( degf ) limbic system components of the limbic system kluver bucy syndrome ♢ bilateral ablation of amygdala ♢ presentation ¤ not afraid of anything ¤ extreme curiosity about everything ¤ forgets rapidly ¤ tendency to place everything in its mouth ¤ has sex drive so strong that it might attempt to copulate with immature animals, animals of wrong sex or d/n species reticular system ( exercise book ) Ventricular system ( video ) ♢ ventricles ¤ third ventricles ¤ foramen of monro/ interventricular foramen ¤ 3rd ventricle ¤ cerebral aqueduct ¤ 4th ventricle ♢ CSF circulation meninges of the brain ♢ dura ¤ perosteal part ¤ meningeal part dural folds falx cerebri tentorium cerebli 11  CNS ♢ arachnoid ¤ arachnoid villi ♢ pia dural venous sinuses ( anatomy zone video) ♢ superior sagittal sinus ♢ infirior sagittal sinus ♢ striate sinus ♢ transverse sinus ♢ sigmoid sinus ♢ occipital sinus ♢ cavernous sinus ¤ recieves opthalmic veins saphenopalatine veins ¤ structures passing through cavernous sinus ( OTOM CAT ) Oculomotor nerve Trochlear nerve Optic branch of the trigeminal nerve Maxillary branch of the trigeminal nerve Carotid artery ( internal ) Abducens nerve ♢ superior petrosal sinus ♢ inferior petrosal sinus blood brain barrier ♢ prevents circulating blood substances from reaching the CSF/ CNS ♢ formed by ¤ tight junctions ¤ basement membrane ¤ astrocytes ♢ circumvalate organs (CVO ) ¤ vascular areas with no BBB ¤ key CVOs ▪ area postrema caudal end of 4th ventricle affected by chemo agents sends signal to vomitting center ▪ OVLT ( organum vasculosum of lamina terminalis ) anterior wall of 3rd ventricle contain osmosensory neurons ▪ subfornical organ ( SFO ) anterior wall of 3rd ventricle responds to angiotensin 2 ▪ median eminence of hypothalamus releases hormones to vascular system to pituitary gland ♢ pineal gland and posterior puitutary also doesnt have BBB cells of cns 12  CNS ♢ neurons ♢ glial cells and their function microglia macroglia ¤ astrocytes ¤ oligodendrocytes ¤ schwann cells ¤ ependymal cell ( khan academy video ) spinal cord ( anatomy zone videos & exercise book ) 13 CNS blood supply ( look at video u downloaded ) anterior circulation ( look at video u downloaded of internal carotid artery ) ♢ internal carotid artery ¤ pathway ¤ branches ▪ ophthalmic artery ▪ ACA 1.cortical branches and their supply olfactory cortex gyrus rectus medial orbital gyrus corpus callosum with exception of the splenium medial part of frontal lobe paracentral lobule 2. central branches and their supply septum pellucidum 14  CNS anterior part of putamen head of caudate nucleus anterio medial aspect of the ant.limb of internal capsule ▪ MCA 1. cortical branches and their supply lateral half of orbital surface of the hemisphere most lateral surface temporal pole and insula 2. central branches and their supply lentiform and caudate post.half of the ant.limb of internal capsule anterior part of the post limb of internal capsule ▪ posterior communicating artery ▪ anterior choroidal posterior circulation ♢ vertebral arteries ¤ anterior spinal artery ♢ basilar arteries ¤ PICA ¤ posterior spinal artery ¤ AICA ¤ labyrinthine artery ¤ pontine artery ¤ superior cerebellar artery ¤ posterior cerebral artery ( PCA ) 1. cortical branches temporal lobe along the inferior border occipital lobe 2. central branches supply most of thalamus most of mid brain most of choroid plexus of 3rd and lateral ventricles 15  CNS circle of willis 16  CNS PNS 1.olfactory nerve pathway 2.optic nerve pathway visual field defects ¤ anopia ¤ bitemporal heminopsia ( hetronymous hemopsia ) ♢ compression of optic chiasm pituitary tumor anterior communicating artery aneurysm ¤ hemonymous heminopsia ¤ quadrantic anopia optic neuritis 3.occulomotor nerve pathway and innervation 17  CNS CN 3 palsy ¤ causes ¤ manifestations eye down, out, ptosis, dilated pupil 4.trochlear nerve pathway and innervation CN 4 palsy ¤ manifestation eye tilted up and outward diplopia head tilts away from affected side to compensate 5.trigeminal nerve (kenhub ) pathway and innervation trigeminal neuralgia ( bootcamp ) ¤ trt ( carbamazepine or oxcarbazepine) ¤ TN secondary to MS Although 18  CNS TN is commonly thought to be due to vascular compression of the CN V root, TN due to MS has a different pathophysiology. Inflammatory plaques in the pons that impact the trigeminal nerve nuclei or compress the trigeminal nerve roots are often implicated in TN secondary to MS usually resulting in bilateral TN b/c symptoms are due to inflammatory plaques, typical trts for TN may be ineffective for TN secondary to MS. 6.abducens nerve pathway and innervation palsy lateral gaze palsy 7.facial nerve (kenhub) the facial nerve nuclei in pons for ¤ upper face recieve dual motor innervation from both motor cortex ¤ lower face recieves motor innervation from only contralateral motor cortex pathway and innervation branches greater petrosal chorda tympani nerve to stapideus muscle To Zanzibar By Motor Car Bell's palsy ♢ peripheral neuropathy of the facial nerve ♢ upper face involvement distinguishes Bell palsy from upper motor neuron d/o (eg, stroke), which spare the upper face ♢ cause 19  CNS ¤ reactivation of a neurotrophic virus, most commonly HSV ♢ trt ¤ High-dose glucocorticoids ¤± Antivirals (eg, acyclovir) ¤ Eye protection (eg, lubrication, taping of eye at night) ♢ prognosis ¤ >85% completely recover with in few weeks with high-dose glucocorticoids ¤ even without trt resolves spontaneously in 70% of cases in 3-6 month ♢ further workup is not recommended when pts have a classic presentation (eg, acute onset, diffuse, peripheral nerve palsy with no systemic findings ) ♢ when do we consider further workup ? ¤ pts with atypical presentation ¤ if facial function has not returned by 4 months ♢ further workup is to exclude other cause of facial nerve palsy i.e ¤ neurologic disease (eg, stroke, GBS) ¤ granulomatous disease (eg, sarcoidosis) ¤ Infections (eg, otitis media, herpes zoster, Lyme disease) ¤ neoplasms (eg, cerebellopontine angle, parotid) 20  CNS 8.vestibulocochlear nerve pathway and innervation 9.glossopharyngeal (kenhub ) pathway and innervation functions ♢ general sensation ¤ tongue( post2/3) ; lingual branch ¤ tonsils ; tonsilar branch ¤ pharynx ( oropharynx, laryngopharynx ) ; pharyngeal branch ¤ middle ear & pharyngotympanic tube ; tympanic branch ¤ external ear ♢ special sensation ; taste from post 2/3 of tongue ; lingual branch ♢ visceral sensation ; carotid body and sinus ♢ parasympathetics ; parotid gland ♢ somatic motor ; stylopharyngeus 10.vagus nerve ( kenhub) pathway and innervation functions ♢ parasympathetic 21  CNS ¤ pharynx, larynx, esophageal plexus, cardiac plexus, pulmonary plexus, celiac plexus ♢ motor ¤ muscles of laynx and pharynx ♢ sensory ¤ afferent autonomic ( unconcious sensation ) viseral sensation from the heart, thoracic cavity, abdomen, carotid body, aortic body, epiglotis ¤ afferent somatic ( concious sensation ) outer ear, external auditory meatus, tympanic membrane 11.accessory nerve pathway and innervation 12.hypoglossal nerve pathway and innervation 22  CNS Types of nerve fibers, their mylination & function A (A alpha- proprioception, motor ) (A beta- touch, pressure ) (A gamma- muscle spindles ) (A delta- temp, pain ) B ( preganglionic sympathetic) C ( pain, postganglionic sympathetic) peripheral nerve damage neurapraxia --> focal demylination axonotmesis --> focal demylination + damage to axon ¤ what changes occur proximal and distal to the injury wallerian degeneration axonal rxn ( cxd) swelling chromatolysis nucleus moves to peripheri neurotmesis sensory receptors mechanoreceptors 1.pacinian corpuscle ( deep touch & deep pressure, vibration ) adapt rapidly/ great at sensing dynamic stimuli 2.ruffini endings ( pressure, joint angle change, slippage of objects along the skin) adapt slowly/ great at sensing static stimuli 3.merkel disc ( pressure, position, detect edges & shapes ) adapt slowly/ great at sensing static stimuli 4.meissner corpuscle ( light touch & position sense ) adapt rapidly/ great at sensing dynamic stimuli 5.free nerve endings thermoreceptors photoreceptors chemoreceptors nociceptors (pain) sensory pathways spinothalamic pathway dorsal column pathway spinocerebellar pathway 23 CNS 24  CNS Basal ganglia function direct pathway indirect pathway mov't disorders of basal ganglia 1. parkinson's dss ( sunstantia nigra) 2. huntington ( caudate neucleus ) ♢ pixorize ♢ motor manifastations of HD ¤ chorea is a core feature of HD and is cxd by sudden involuntary movements of the face, limbs, and trunk. early in the dss course, chorea may be mild and mistaken for restlessness, and pts may try to hide movements as purposeful ¤ hyperreflexia ¤ delayed initiation of voluntary saccades ¤ motor impersistence 25  CNS ♢ look at video chorea ( dowloaded on ur phone ) https://youtu.be/7FdGWpO9vvY?si=1fG5cX1oWvPlxbRZ 3. hemiballismus (subthalamic nuclei) 4. wilsons dss( GBI, striatum) contribution of Cerebellum to motor mov't cerebellar hemisphere d/o manifestations ( DANISH ) ¤ disdiadochokinesia ¤ ataxia ♢ differentiating cerebellar ataxia vs sensory ataxia by romberg test sensory ataxia (peripheral nerve or dorsal column damage) ♢ hereditary ataxias ataxia telangiectasia friedreichs ataxia ¤ nystagmus ¤ intention tremor ¤ scanning speech/ dysarthria ¤ hypotonia cerebellar vermis ( involved in coordination of the vestibular system, eye movements, balance, and complex and sequential movements) ♢ d/o manifestation ¤ downbeat nystagmus ¤ head bobbing ¤ truncal ataxia flocculonodular lobe ( involved in regulating balance, ocular movements, and gaze stability) ♢ d/o manifestation ¤ head bobbing ¤ truncal ataxia ¤ upbeat or rebound nystagmus, not the downbeat nystagmus alcoholic cerebellar degeneration Pathways pyramidal tract ¤ corticospinal tract ¤ corticobulbar tract extrapyramidal tracts ¤ rubrospinal tracts 26  CNS ¤ tectospinal ( collicospinal ) ¤ vestibulospinal ¤ olivospinal😢 ¤ reticulospinal😢 upper and lower motor neuron symptoms signs of UMN lesions 1.affects large grp of muscles 2.atrophy is rare 3.graded weakness( paresis ) 4.absence of fasciculation 5.absence of fibrillation 6.hypertonia 7.hyperreflexia 8.spasticity 9.clonus 10.babinski sign signs of LMN lesions 1.affects small grp of muscles 2.atrophy 3.profound weakness 4.fasciculation 5.fibrillation 6.hypotonia 7.hyporeflexia Pronator drift 27  CNS Infectious 1.meningitis normal csf analysis vs bacterial Tb/ cryptococcal viral Bacterial meningitis ♢ should be suspected in pts presenting with ♢ most common cause ¤ pneumococcal meningitis ¤ meningococcal meningitis early meningococcal infection presents w__w/c can be mistaken for pharyngitis, key distinguishing features are__ complications of meningococcemia postexposure trt for who and what ♢ conditions in w/c we do head CT before LP (FAILS) ¤ if we delay LP to do imaging should we delay antibiotics? ♢ empiric antibiotic for ¤ age 2-50 ¤ > 50, pregnant ¤ immunocompromised ¤ neurosurgury/ penetrating skull trauma ♢ who should recieve dexamethasone and why ♢ long term complications of meningitis in children ¤ complications are more likely to occur in w/c grp ♢ bacterial meningitis in children > 1 month ¤ common etiology ¤ presentation ¤ approach ¤ indication for CT ¤ trt TB meningitis ♢ occurs in _ % of pts w disseminated Tb ♢ w/c pts are at increased risk of developing Tb meningitis ♢ do most pts with Tb meningitis have pulmonary symptoms? ♢ clinical presentation ♢ diagnosis ¤ LP ¤ imaging ( what would you see) 28  CNS ¤ how helpfull are TST & IGRA ♢ trt Cryptococcal meningitis ♢ presentation ♢ diagnosis ¤ LP csf analysis may present similar to Tb meningitis differentiating them is hard indian ink stain ♢ trt ¤ induction ¤ consolidation ¤ maintenance Viral meningitis ♢ common causes ¤ enteroviruses ¤ mumps ¤ acute hiv infection 2.encephalitis HSV encephalitis ♢ primary vs reactivated infection ♢ presentation ♢ diagnosis ¤ imaging ( what will you see) ¤ CSF analysis ( what will you find) ♢ trt Autoimmune encephalitis ♢ Anti-NMDA receptor encephalitis ¤ is a form of autoimmune encephalitis syndrome cxd by psychiatric symptoms (eg, anxiety, psychosis), cognitive dysfunction (eg, memory impairment), seizure, autonomic instability, dystonia, and rigidity. ¤ It occurs most commonly in young women (median age of 21) and is associated with ovarian teratoma in >50% of cases. ¤ diagnosis can be confirmed by the presence of CSF antibodies to the GluN1 subunit of the NMDAR ¤ trt immunosuppressive treatment ( Regardless of the presence of a tumor ) tumor removal has been associated with better outcomes ¤ recovery is often slow, but 4 of 5 patients recover with minimal sequelae within 2 years. 3.brain abcess common etiologies how do the bacteria get access to the brain direct spread from__ hematogenous spread from presentation 29  CNS diagnosis treatment emperic antibiotic choice(metri+ceftra+vanco) aspiration of the lesion 30  CNS hydrocephalus communicating ♢ common cause 1. scarring after meningitis 2. choroid plexus papilloma (CPP) a benign intraventricular mass that causes increased production of CSF most common in infants diagnosis U/S of head ; enlarged ventricles with an intraventricular mass MRI ; confirmatory treatment surgical resection non communicating ♢ common causes 1. congenital ¤ aqueductal stenosis X linked or inflammation from in utero infections ¤ chiary malformation ¤ dandy walker malformations 2. acquired ¤ anything compressing csf outflow tract ¤ intraventricular hemorrhage in premature infants (IVH) ¤ vitamin K deficiency bleeding (VKDB) Classic VKDB presents in the first week of life with easy bruising, mucosal & gastrointestinal bleeding. Late-onset VKDB occurs between age 2 weeks and 6 months and is more commonly associated with intracranial hemorrhage w/c can block csf flow leading to obstructive hydrocephalus presentation of hydrocephalus in children ♢ Head examination ¤ rapidly enlarging head circumference &/or macrocephaly ( crossing multiple major percentiles ) ¤ prominent scalp veins ¤ full anterior fontanelle (if open) ♢ Signs of increased ICP ( more commonly seen once the anterior fontanelle closes ) ¤ headache, vomiting ¤ papilledema, impaired upward gaze 31  CNS ¤ hypertension, bradycardia ♢ Lower extremity weakness & spasticity ♢ developmental delay approach to a child with suspected hydrocephalus ♢ first step is neuroimaging ¤ In an infant with an open fontanelle ultrafast MRI or ultrasonography of the head ( visualization of the posterior fossa is superior with MRI ) ¤ CT scan is reserved for pts with acute signs of rising ICP due to risk of radiation ventriculoperitoneal shunt pseudotumor cerebri/ idiopathic intracranial hypertension ♢ risk factors ¤ women of childbearing age ¤ Recent weight gain/obesity ¤ Medications (eg, retinoids/vitamin A, tetracyclines, growth hormone) ♢ Pathophysiology ¤ Impaired CSF resorption & intracranial venous hypertension ♢ presentation ¤ signs of ICP ¤ pulsatile tinnitus ( whooshing sound ) ¤ Visual changes transient visual loss ( due to acute compression of the optic nerve ) blurry vision ( due to pappiledema ) enlarged physiologic blind spot (enlargement of the optic nerve due to papilledema) diplopia due to abducens nerve [CN VI] palsy (its long course through the skull ) ♢ diagnosis ¤ Papilledema & enlarged blind spots ¤ MRI to rule out mass lesions/hydrocephalus 32  CNS ¤ MR venography to rule out venous thrombosis ¤ LP : elevated opening pressure (>250 mm H2O) ♢ treatment ¤ carbonic anhydrase inhibitor (acetazolamide, topiramate ) ¤ wt loss normal pressure hydrocephalus ( NPH ) ♢ what is it ♢ presentation (DUG) ♢ diagnosis ¤ enlarged ventricles out of proportion to the underlying brain atrophy/ without sulcal enlargement ¤ marked improvement in gait with spinal fluid removal ♢ how to differentiate it from pseudotumor cerebri ♢ trt (vp shunt ) hydrocephalus ex vacuo ♢ what is it ♢ common causes ¤ age ¤ disease HIV , Alzhiemers, picks dss 33  CNS mid brain dss, structures affected & presentation 1.benedikt syndrome 2.claude synd ( claude spares crus cerebri) 3.weber synd ( weber spares red nucleus ) 4.parinoud synd pons dss, structures affected & presentation 1.millard gubler/ ventral pontine synd 2.foville synd/ paramedian pontine synd 3.raymond synd/ ventromedial pontine synd 4.marie-foix synd/ lateral pontine synd 5.locked in synd medullary dss, structures affected & presentation 1.medial medullary synd 2.lateral medullary synd/ wallenberg synd rule of four 34  CNS Tumors primary vs metastatic ♢ metastatic 50% ¤ common sources lung > breast > unknown primary > melanoma > colon ¤ present as multiple/ solitary well circumscribed lesion at grey-white junction ¤ how to differ it from neurocysticercosis on imaging ¤ trt surgical resection is recommended for solitary brain metastasis in pts with good performance status and stable extracranial disease whole brain radiation therapy In pts with multiple brain metastases ♢ primary tumors 50% ¤ adult 1.pituatary adenoma 2.meningioma ▪ risk factors female sex, old age, genetic predisposition ( NF2, schwannoma ) radiation exposure ▪ can also occur in spinal meninges 3.hemangioblastoma 4.glioblastoma multiforme 5.oligodendroglioma 6.schwanoma ¤ pediatric 1.craniopharyngioma ♢ Bimodal age distribution (age 5-14 & 50-75) 35  CNS 2.pinealoma 3.medulloblastoma 4.pilocytic astrocytoma differentiating medulloblastoma from pilocytic astrocytoma 5.ependymoma 36  CNS Aneurysms ♢ saccular/ berry aneurysm ♢ charcout bauchard aneurysm Heamorrhage ♢ Epidural hemorrhage cause presentation imaging finding 1st line trt for pts with epidural hematoma is urgent craniotomy ♢ subdural hemorrhage cause presentation 37  CNS imaging finding ¤ acute ¤ chronic mngt ¤ urgent surgical evacuation if there is evidence of neurological deterioration the SDH is ≥ 10 mm midline shift ≥ 5 mm on brain scan ♢ subarachnoid hemorrhage cause ♢ ruptured saccular/ berry aneurysms ¤ 80% of nontraumatic subarachnoid hemorrhages ♢ AVM ¤ 10% of nontraumatic subarachnoid hemorrhages ¤ appear as foci of calcification and hyperattenuating vascular channels ♢ ruptured mycotic aneurysm ¤ a rare cause of nontraumatic subarachnoid hemorrhages. mycotic intracranial aneurysms result from infected emboli, most often secondary to infective endocarditis ♢ Intracranial artery dissection ¤ rare cause of subarachnoid hemorrhage. ¤ majority of cases occur in people between the ages of 35–50 years ¤ is usually preceded by a history of trauma, exertional activity, or cerebral artery stretching presentation compared to meningitis SAH is cxd by dramatic onset and rapidly progressive severity of symptoms imaging finding 38  CNS if u highly suspect SAH but CT is negative what do you do what LP finding is suggestive of SAH how to differ traumatic LP from SAH complications of SAH ¤ rebleeding ; first 24 hrs ¤ vasospasm 4-12 days what do you do to prevent it from happening ♢ Intraparynchymal heamorrhage ¤ lobar hemorrhage ▪ causes 1.HTN ( most common cause ) 2.trauma 3.cerebral amyloid angiopathy (CAA ) is a vasculopathy cxd by beta amyloid deposition within small to medium sized cerebral blood vessels. is associated with Alzheimer dementia usually seen in > 65 age ICH due to CAA most often involves the occipital and parietal lobes, usually sparing the ventricles and deep brain structures (w/c helps differentiate it from hypertensive hemorrhage) 4.vascular causes aneurysms AVM (most common cause of intracerebral hemorrhage in children) 39  CNS vasculitis 5.coagulopathies ¤ lacunar hemorrhage ▪ Causes 1.HTN 2.charcout bauchard aneurysm 3.drug use cocaine inhibits the reuptake of serotonin, norepinephrine, and dopamine in the CNS which results in sudden onset of hypertension (due to increased sympathetic activation) as well as cerebral vasospasms cocaine induced ICH should be suspected in Young age Location ; most commonly seen in subcortical locations (eg, thalamus) and has a higher risk of associated intraventricular hemorrhage Absence of typical risk factors ; i.e Chronic hypertension Sympathetic activation ; acute HTN, tachycardia, mydriasis & hyperthermia ♢ Intraventricular hemorrhage cause ¤ due to ruptured germinal matrix vessels 40  CNS ¤ the germinal matrix is a fetal structure that eventually gives rise to neurons; it contains fragile vasculature that is prone to rupture with acute changes in cerebral perfusion ¤ Involution of the germinal matrix begins at gestational age 32 wks therefore, prematurity is the primary risk factor for IVH. presentation ¤ often asymptomatic ( 50% ) ¤ if symptomatic typically occurs in the first 3- 4 days of life with anemia, tachycardia bulging fontanelle, rapidly increasing head circumference nonspecific signs such as apnea, hypotonia, decreased movements & seizure diagnosis ¤ cranial ultrasonography performed if symptomatic or as routine screening if 30 minutes prior to injury focal deficits signs of skull fracture ♢ trt ¤ symptom mngt ( NSAIDS ) ¤ physical and cognitive rest for 24-48 hours ¤ gradual return- to-play protocol with slowly increasing physical intensity post concussion syndrome ( PCS ) ♢ most patients 43  CNS who follow a gradual return-to-play protocol after concussion have symptom resolution in 4 weeks) concussion symptoms after mild TBI ♢ risk factors ¤ nonadherence to gradual return-to-play protocol after concussion ¤ history of multiple concussions ♢ trt ¤ symptomatic care ( most pts improve within 3 months ) Diffuse axonal injury ♢ what is it ¤ wide spread shearing of white matter tracts ♢ etiology ¤ coup counter coup injury, mva, penetrating/ blast trauma ♢ presentation ¤ causes severe neurologic impairment in the absence of major CT scan findings. ♢ diagnosis ¤ initial test in TBI is CT is unremarkable in diffuse axonal injury ¤ MRI diffuse punctate hemorrhages at grey- white junction blurring of the gray-white interface (due to edema) ¤ histology axonal bulb formation accumulation of axonal transport protein TBI ♢ neurologic injury from TBI occurs in 2 phases ¤ primary injury caused by the mechanical impact ¤ secondary injury caused by subsequent local and/or systemic insults 1. acute traumatic coagulopathy ▪ cxd by increased activation of the coagulation pathway due to severe tissue injury leading to Hypocoagulability Hyperfibrinolysis, which may break down necessary clots ▪ this changes lead toworsening of existing ICH or cause delayed ICH 2. secondary insult of ischemia ♢ mngt of TBI 44  CNS 1. Prevent ICH ¤ antifibrinolytic therapy (ie, tranexamic acid) within first 3 hr ¤ reversal of preexisting anticoagulation 2. Maintain CPP (= MAP − ICP) ¤ maintain MAP ▪ isotonic fluids, vasopressor therapy ¤ reduce ICP ▪ ↓ Brain parenchymal volume osmotic therapy (eg, hypertonic saline, mannitol) to extract water ▪ ↓ Cerebral blood volume Head elevation to ↑ venous outflow Sedation to ↓ metabolic demand Hyperventilation to ↓ PaCO2, resulting in vasoconstriction ▪ ↓ CSF volume CSF removal (eg, external ventricular drain) ▪ ↑ Cranial volume ; Decompressive craniectomy 3 Other measures ¤ prevent seizures (eg, levetiracetam, phenytoin) ¤ control blood glucose (eg, insulin to target 140-180 mg/dL glucose) ¤ maintain normothermia (eg, antipyretics, surface-cooling devices) N;B --> paroxysmal sympathetic hyperactivity (PSH) ♢ occurs in ~ 10%-20% of patients with severe TBI ♢ occurs following damage to cortical areas that are responsible for modulating and inhibiting lower sympathetic centers (eg, in the hypothalamus, brainstem, and spinal cord) ♢ the resulting sympathetic hyperactivity manifests as rapid onset episodes of ¤ tachycardia, HTN, tachypnea often accompanied by fever & diaphoresis ¤ episodes can last up to 20-30 min ¤ usually triggered by external stimuli (eg, bathing, repositioning) but may occur spontaneously. ♢ diagnosis ; clinical ♢ treatment ¤ supportive (eg, avoiding triggers, treating fever) ¤ medication (eg, opioids, GABA-agonists, α2- agonists) to abort and/or 45  CNS prevent episodes Pediatric TBI ♢ High-risk features warranting consideration of imaging in children age < 2 ¤ altered mental status (fussy behavior) ¤ loss of consciousness ¤ severe mechanism of injury (fall >0.9 m [3 ft], high impact, MVC) ¤ nonfrontal scalp hematoma ¤ palpable skull fracture ♢ High-risk features warranting consideration of imaging in children age ≥2-18 ¤ altered mental status ¤ Loss of consciousness ¤ Severe mechanism of injury (eg, fall >1.5 m [5 ft], high-impact hit, MVA ) ¤ Vomiting or severe headache ¤ Signs of basilar skull fracture ♢ in pts with no high risk features imaging should be avoided and mngt should be reassurance and discharge home 46  CNS increased ICP & herniation ♢ signs of ICP 1.headache ¤ classically worsen during recumbent positioning (eg, at night, when waking in the morning ) 2.projectile vomiting 3.pappiledema 4.cushing triad HTN, bradycardia, irregular breathing 5.ipsilateral fixed,dilated pupil, down & out eye +/- ptosis 6.CN6 palsy 7.posturing ¤ decorticate ¤ decerebrate ♢ interventions for lowering ICP( refer TBI ) ♢ Herniation syndromes 1.subfalcine herniation of ¤ cingulate gyrus underneath falx cerebri presentation ¤ Contralateral leg weakness (ipsilateral ACA compression) ¤ no pupillary involvement, consciousness often preserved 2.uncal herniation herniation of ¤ uncus (medial temporal lobe) under tentorium cerebelli presentation ¤ Ipsilateral dilated & fixed pupil ipsilateral oculomotor nerve [CN III] compression ¤ kernohans phenomena Early: contralateral hemiparesis (ipsilateral cerebral peduncle compression) Late: ipsilateral hemiparesis (contralateral cerebral peduncle compression) 47  CNS ¤ homonymous heminopsia with macular sparing PCA compression 3.central/ tentorial herniation herniation of ¤ Caudal displacement of diencephalon & brainstem presentation ¤ Midsized, fixed pupils (impairment of both parasympathetic & sympathetic nerve fibers innervating the pupil) ¤ Unconsciousness (dysfunction of the ascending reticular activating system responsible for arousal) ¤ Decorticate (flexor) → decerebrate (extensor) posturing 4.tonsilar herniation herniation of ¤ cerebellar tonsils through foramen magnum presentation ¤ Coma ¤ loss of CN reflexes ¤ flaccid paralysis ¤ respiratory arrest 48  CNS Headache differentiating headaches based on Presentation, duration, other neurologic symptoms, genetic predisposition, triggers, treatment 1.Tension headache 2.Migraine headache ♢ pathophysiology ♢ diagnosis ¤ clinical ¤ neuroimaging maybe indicated in differences compared to prior headaches: rapidly increasing frequency, intensity abnormal neurologic examination (Seizure, changes in consciousness, specific deficits) signs of increased ICP new at age >40, sudden onset, trauma, present on awakening ♢ migraine in children vs adults Children adults & adolescents equal incidence in boys & --------------- F>M girls until puberty autonomic symptoms i.e ------------------ not typically found facial sweating tearing nasal congestion are common ♢ migraine in pregnant ¤ make sure to exclude other causes of headache i.e preeclamsia cerebral venous thrombosis ♢ treatment ¤ abortive ▪ for non pregnant 1st line dark,quite room, NSAIDs, acetaminophen refractory triptans, ergotamine ▪ pregnant 49  CNS 1st line acetaminophen pts who do not improve with acetaminophen low-potency opioid (acetaminophen-codeine) antiemetics (eg, promethazine) caffeine/butalbital NSAIDs ( 2nd TM only!! ) avoided in 1st & 3rd TM due to risk of fetal complications spontaneous abortion premature ductus arteriosus closure oligohydramnios renal dysfunction if all other options fail to improve symptoms potent opioids (eg, oxycodone) S/I worsen GI symptoms (eg, constipation, nausea) during pregnancy ¤ prophylactic medication ▪ beta blockers ( 1st line prevention during pregnancy ) ▪ amytriptiline ▪ topiramate ▪ considered for pts who have frequent (>4/month) or long-lasting ( >12 hours) episodes disabling symptoms that prevent regular activities despite abortive trt do not respond to abortive medications ♢ women who have migraine with aura are at increased risk of ischemic stroke so estrogen-containing contraceptives are contraindicated in this pts 3.Cluster headache ♢ trt for acute vs preventive trt( verapamil ) 50  CNS 4.Medication overuse headache ( MOH ) ♢ cxd by chronic ( ≥3 months ), near-daily headache in the setting of regular use of acute headache medications in patients with a preexisting headache disorder. ♢ presentation ¤ headache that is present upon awakening & brief symptom relief followed by rebound pain. ¤ the headaches mimic a migraine-type or tension-type headache ♢ overuse of any type of acute headache medication can lead to MOH but butalbital-containing products i.e ¤ acetaminophen ¤ opioids are the most commonly implicated ♢ mngt ¤ cessation of the culprit drugs 51  CNS Cerebral vein & venous sinus thrombosis risk factors ♢ thrombophilia (eg, factor V Leiden) ♢ pregnancy & postpartum ♢ oral contraceptive pills ♢ malignancy ♢ Infection pathophysiology ♢ venous sinus obstruction impairs CSF absorption, causing increased ICP ♢ venous sinus and isolated cerebral vein obstruction impedes blood return, causing increased venule/capillary pressure, resulting in ¤ decreased cerebral perfusion (cytotoxic edema) and ¤ blood-brain barrier disruption (vasogenic edema) presentation ♢ Headache, ↑ ICP (eg, vomiting, papilledema) ♢ Focal neurologic symptoms, seizures ♢ Encephalopathy diagnosis ♢ CT scan of the head is normal in approximately 30% of cases. ♢ When clinical suspicion remains high,MRI of the brain with MR venography is the next best step (highest sensitivity) treatment ♢ anticoagulation cavernous sinus thrombosis ( CST ) infective vs non infective CST 1.Infective CST ♢ common microorganisms are ¤ staph.aureus (70%) ¤ strep ♢ usually occurs from ¤ orbital cellulitis ¤ sinusitis ( sphenoid & ethmoid ) ¤ facial skin infection ( the danger triangle ) 2. non infective CST ♢ common causes ¤ hypercoagulable states ¤ carotid cavernous fistula ¤ nasopharyngeal carcinoma presentation ♢ even though CST started on one side it becomes bilateral with in 48 hrs due to connection of the two cavernous sinuses by inter cavernous sinus ♢ severe headache ♢ periorbital edema, proptosis, chemosis 52  CNS ¤ secondary to impaired venous flow in the orbital veins ♢ cranial nerve III, IV, V, and VI deficits ♢ signs of increased ICP prognosis ♢ 30% mortality rate diagnosis ♢ MRI with magnetic resonance venography trt (broad-spectrum IV antibiotic + prevention of herniation ) 53  CNS Stroke what is stroke ♢ sudden onset focal neurologic deficit caused by vascular origin and lasts for > 24 hr stroke vs TIA risk factors for stroke & TIA ♢ modifiable ¤ HTN - 4x ¤ smoking - 2.5x ¤ DM - 2x ¤ hypercholestrolemia - ≤2× ¤ alcohol intake - variable effect ¤ life style, obesity - small effect ♢ non modifiable TIA vs Todd paralysis ♢ although both of these conditions can cause headaches, aphasia, and limb weakness in TIA neurological symptoms usually localize to a single vascular territory rather than multiple TIAs rarely cause altered mental status and unconsciousness risk of stroke following TIA ♢ ABCD2 approach to pt with TIA TIA treatment ♢ modifying risk factors ♢ starting aspirin and statin ♢ improving blood pressure control 54  CNS classification of Stroke 1.Ischemic ♢ histopathologic timeline ¤ 4-5 min irriversible neuronal injury ¤ 1hr cytotoxic edema due to failure of ATP gated ion channels ¤ 12-24 hr red neurons, pyknosis ¤ 1-3 days BBB disruption vasogenic edema neutrophil liquefactive necrosis 55  CNS ¤ 3-7 days increase microphage and microglia density ¤ 1-2 week reactive gliosis ¤ > 2week cystic spaces surrounded by glial scarring ♢ types ¤ thrombotic ¤ embolic ▪ cardio embolic stroke most common causes of cardio embolic stroke i. atrial fibrillation risk of stroke CHA2DS2 VAS score chronic anticoagulation is indicated for men with a total score ≥2 and women with a total score ≥3 direct oral anticoagulants (eg, apixaban, rivaroxaban, dabigatran) are typically used for chronic anticoagulation ii. rheumatic heart dss iii. prosthetic valves ▪ artery to artery embolic stroke any diseased vessel can be embolic source ¤ global hypoperfusion 56  CNS ▪ bilateral wedge shaped infarct in watershed areas ▪ bilateral weakness of shoulders and thighes ( man in a barrel appearance) ▪ w/c areas of the brain is highly suceptable to hypoxia hippocampus cerebellum ( purkinge fibers) 2. hemorrhagic (pls refer hemorrhage part written previosly) Classical time course of strokes by etiology ♢ Hemorrhagic stroke ¤ evolves over minutes to hrs pts initially develop focal neurologic symptoms localized to the site of the bleed, as the hemorrhage expands, focal deficits are then quickly followed by findings suggestive of increased ICP this finally progresses to decreased consciousness ♢ embolic ¤ symptom onset is abrupt but is usually maximal at the start increased ICP is uncommon. ♢ thrombotic ¤ symptoms may alternate with periods of improvement ( stuttering progression) Stroke syndromes ♢ cortical 1.ACA syndrome ¤ presentation abulia ( basal forebrain ) contralateral hemiparesis ( leg > arm& face) contralateral hemisensory loss ( leg > arm& face) urinary incontinence 57  CNS gait apraxia ( supplementary motor area) transcortical motor aphasia 2.MCA syndrome ¤ presentation contralateral hemiparesis ( arm & face > leg) contralateral hemisensory loss ( arm & face > leg) conjugate deviation to the side of lesion ( FEF) broca's aphasia, wernickes aphasia, global aphasia contralateral homonymous hemionopia, quadrantopia ( optic radiations ) gerstmann synd. ( angular gyrus ) contralateral hemineglect if non dominant hemisphere is affected 3.PCA ¤ presentation contralateral homonymous hemionopia with macular sparing ¤ even though not cortical signs PCA stroke also results in medbrain dss refer mid brain portion ♢ lacunar ¤ lacunar ischemic microatheroma lipohyalinosis ¤ lacunar hemorrhagic charcout buchard aneurysm hemorrhage ¤ affected areas i. thalamus ▪ thalamic pain syndrome a central neuropathic pain syndrome that can develop after a stroke impacting the thalamus cxd by unilateral severe paroxysmal burning pain over affected areas w/c is classically exacerbated by light touch (allodynia) pain can be triggered by other sensory modalities (eg, sound, taste). ii. caudate nucleus iii. globus palidus iv. putamen Putaminal hemorrhage almost always involves the adjacent internal capsule this leads to contralateral hemiparesis and hemianesthesia (due to disruption of the corticospinal and somatosensory fibers in the posterior limb) and conjugate gaze deviation toward the side of the lesion (due to damage 58  CNS of frontal eye field efferents in the anterior limb). v. internal capsule vi. subthalamic nuclei vii. pons ¤ presentations absence of cortical signs (eg, aphasia, agnosia, neglect, apraxia, hemianopia), seizure or mental status changes Approach to suspected stroke 1.assessment of ABC 2.non contrast CT & lab studies ( cbc, RBS, coagulation panel, lipid profile...) ♢ why non contrast CT ♢ hyperdense (white) area on CT indicates hemorrhagic stroke ¤ reverse coagulopathy ( if it is warfarin related ICH) ▪ FFP, PCC ( prothrombin complex concentrates), vit k ¤ BP control ( goal SBP 140- 160 ) ¤ mngt of elevated ICP ¤ in addition to above urgent surgical decompression and clot evacuation are indicated in cerebellar (cerebellum) hemorrhage with ▪ signs of neurologic deterioration (eg, progressive lethargy, obtundation, coma). 59  CNS ▪ radiologic evidence of bleed >3 cm brainstem compression obstructive hydrocephalus ♢ CT is often normal in early ischemic stroke ( 185/110 mm viii. Current anticoagulant use with INR >1.7, PT >15 sec, or ↑ active PTT ix. Glucose /= 24 hrs not eligible for thrombolytic no need for CT angiography only standard post stroke mngt antiplatelet therapy investigation for embolic source etc 60  CNS pediatric stroke ♤ ischemic stroke ♢ risk factors ¤ cardiac congenital heart dss ( causing paradoxical embolism ) bacterial endocarditis ¤ vascular non inflammatory arterial dissection inflammatory vasculitis ¤ hematologic sickel cell dss 61  CNS hypercoagulable states ( protein c or s deficiency ) ♢ acute ischemic stroke in young children (< 6 yrs) presents different than older children and adults. they are more likely to have non localizing symptoms i.e ¤ headache (25-50%) ¤ seizures (15-25%) ¤ altered mental status, lethargy in addition to the classic focal neurologic deficits ♢ approach to children with acute ischemic stroke ¤ urgent MRI and MR angiography is more sensitive than CT scan for diagnosis of AIS in children ♤ hemorrhagic stroke ♢ risk factors ¤ vascular malformations AVM ( isolated or associated with HHT ) aneurysms ¤ hematologic dss hemophilia sickel cell dss N;B --> 62  CNS Seizures what is seizure causes os seizure ( VITAMIn D&E ) classification ♢ focal vs generalized ♢ provoked vs unprovoked what is jacksonian march diagnostic evaluation of a first-time seizure in an adults 1. exclude metabolic causes (eg, hypoglycemia, electrolyte disturbances) 2. toxicology screen 3. once metabolic and toxic etiologies are excluded as the cause of seizure most patients require neuroimaging 4. LP can be considered after neuroimaging has ruled out a space-occupying lesion but it is typically reserved for patients with suspected meningitis 5. EEG ; helps to stratify patient risk to determine if antiepileptic agents are needed febrile seizures ♢ common age 6month- 5yrs ♢ diagnostic criterias ¤ no previous afebrile seizure ¤ no signs of CNS infection ¤ no acute metabolic cause (eg, hypoglycemia) ♢ simple febrile seizure vs complex febrile seizure ¤ simple febrile brief generalized, non reoccuring ¤ complex febrile long lasting, reoccuring ♢ trt ¤ abortive therapy (≥5 min) ¤ symptomatic care (eg, antipyretics) ¤ reassurance and discharge ♢ Hospitalization & observation are required ¤ afebrile children with first-time seizure ¤ febrile seizures who have partial or focal seizure activity prolonged seizure (> 15 min) delayed recovery to baseline or postictal focal neurologic deficits ♢ LP for febrile seizure for pts with persistent neurologic abnormalities those already on antibiotics that could mask signs/symptoms of meningitis infants age 6-12 months with incomplete immunization against strep pneumo, HIb 63  CNS ♢ postictal lab abnormalities seizure vs syncope what is epilepsy ♢ 2 or more unprovoked seizures separated by > 24hrs ♢ 1 seizure with high risk for subsequent seizures epilepsy syndromes ♢ juvenile myoclonic epilepsy ( JME ) ♢ lennox gastaut synd ♢ mesial temporal lobe epilepsy ( MTLE ) status epilepticus ♢ what is it ♢ pts are at increased risk of developing permanent injury due to excitatory cytotoxicity. cortical laminar necrosis is the hallmark of prolonged seizures and can lead to persistent neurologic deficits and recurrent seizures ♢ trt ¤ stabilize circulation, airway & breathing ¤ abort seizure ( IV benzodiazepines repeat administration until termination of seizure activity) give IM midazolam if IV access cannot be gained ¤ prevention of reccurence ( AED ) 64  CNS ♢ following trt pt with status epilupticus usually regain responsiveness in 10-20 mins ¤ if this occurs neuroimaging (eg, brain MRI, head CT) should be performed to evaluate for any underlying structural abnormality, hemorrhage, or area of ischemia ¤ but if this doesn't occur it could be due to sedation due to persistent effects of benzodiazepines or ongoing seizure activity without physical manifestations ¤ to differentiate b/n the two states we need to do EEG. if EEG shows seizure activity despite benzodiazepines and AED we proceed to continuous infusion of benzodiazepines propofol or pentobarbital in refractory cases. N;B --> PNES Antiepileptic medications ♢ drugs inhibiting the glutaminergic pathway ¤ sodium channel blockers ( Fenet on Top of Lam in Carbon Valley ) ▪ carbamezapine ▪ valproate ▪ lamotrigine ▪ topiramate ▪ phenytoin phenytoin overdose (https://youtu.be/7BrBRISXe7k?si=ymXP-O09Ad3fd1zd) ¤ calcium channel blockers ▪ gabapentin ▪ ethosuximide ¤ SV2A( calcium binding protien ) blockers 65  CNS ▪ levitracetam ♢ drugs enhancing the GABA pathway ¤ GABA-A agonists ▪ Benzodiazepines short acting ( TM ) Triazolam Midazolam intermidiete acting ( COLA ) Clonazepam Oxazepam Lorazepam Alprazolam long acting ( DCF ) Diazepam Clordiazipoxide flurazepam not metabolized by liver (LOT ) Lorazepam Oxazepam Temazepam Barbituates ¤ GABA transaminase inhibitors vigabatrin valproate ¤ GABA reuptake inhibitors tiagabin Myoclonus involuntary muscle contraction that results in movement of limbs or joints causes ♢ genetic disorders ♢ seizures ♢ medications ♢ prolonged hypoxia/ posthypoxic myoclonus (PHM) ¤ commonly occurs after cardiac arrest ¤ PHM can be subdivided into acute and chronic forms 1. myoclonus status epilepticus (MSE) ▪ acute form of PHM that typically develops within 24 hrs after the initial hypoxic insult while the patient is still unconscious. ▪ cxd by generalized (often symmetric) myoclonus that typically involves 66  CNS the axial, limb, and facial muscles ▪ intermittent eye opening, upward gaze deviation & swallowing mov'ts are also common ▪ https://youtube.com/shorts/PFyFVkKQ_8Q? si=52j0tH_UqmWxivQz 2. Lance-Adams syndrome ▪ chronic form of PHM, presents days to weeks after the initial insult once the pt has regained consciousness ▪ It is typically focal in nature and exacerbated by action ▪ https://youtu.be/ySLS6KF9KPI? si=TZ4desrj0BIcgPDM ¤ EEG should be obtained to help distinguish between other forms of seizure and PHM ¤ treatment ▪ administration of antiepileptic agents (eg, clonazepam, levetiracetam) and supportive care 67  CNS Demyleting dss CNS 1.Multiple sclerosis ♢ pixorize ♢ risk factors ¤ Female, HLA-DRB1 ¤ Environmental factors (United States, Europe, Australia) ¤ Low vitamin D levels ¤ Epstein-Barr infection ♢ pregnancy is protective for multiple sclerosis (possibly due to the immunosuppressive effects of pregnancy), there is an increased risk of both the initial presentation and subsequent relapses in the early postpartum period. ♢ treatment ¤ acute exacerbation high dose glucocorticoids ACTH is sometimes used to promote the release of endogenous steroid Plasmapheresis should be considered in patients with MS flare who are refractory to corticosteroid therapy ¤ dss modifying drugs natalizumab fumarate beta interferons glatiramer ¤ symptom mngt 68  CNS Baclofen, an agonist at the GABA-B receptor Tizanidine, an alpha-2 adrenergic agonist N:B--> Depression has been found in up to two-thirds of pts with MS and is the most common psychiatric complication 2.ADEM ( acute disseminated encephalomyelitis ) ♢ osmosis ♢ how to differentiate it from MS A rare immune-mediated, demyelinating CNS disease caused by cross-reaction hypersensitivity between viral antigens and myelin. It usually develops after viral infections or, rarely, after vaccination. Clinical features resemble those of multiple sclerosis (e.g., optic neuritis). 3.Central pontine myelinosis ♢ Acute, symptomatic hyponatremia requires a prompt increase in the serum sodium concentration with 3% or hypertonic saline at a rate of no more than 0.5 mEq/L/hr to avoid causing central pontine myelinosis 4.Progressive multifocal leucoencephalopathy (PML ) 69  CNS Degenerative dss Degenerative dss of basal ganglia 1.parkinsons dss ♢ pixorize ♢ etiology ¤ 85 - 90% sporadic ¤ 10 - 15% familial ¤ environmental cases MPTP heavy metals, pesticides, cyanide etc ♢ protective factors ¤ smoking, caffiene intake ♢ presentation ¤ premotor symptoms ¤ motor symptoms ▪ cardinal motor symptoms ( TRAP ) ♧ types of tremors parkinson dss tremor resting tremor asymmetric ( It often occurs asymmetrically or involves one hand before the other) hands and legs essential tremor bilateral action tremor of the hands head tremor without dystonia Hands > arms > head >> legs no other neurologic signs Improves with alcohol family hx often present more pronounced at the end of goal-directed movements and improves, but may not completely abate, at rest. treatment anticonvulsants: primidone beta blockers: propranolol cerebellar tremor intention tremor usually associated with other cerebellar symptoms orthostatic tremor legs & trunk occurs only when standing functional (psychogenic) tremor 70  CNS abrupt onset and cessation present at rest and during mov't, stops with distraction (ie, during examination) not associated with other neurologic findings physiologic tremor most common cause of action tremor low amplitude, not visible under normal conditions ↑ With sympathetic activity (eg, drugs, hyperthyroidism, anxiety, caffeine) worse with movement common causes of enhanced physiologic tremor □ physiologic conditions stress, anxiety □ medical conditions thyrotoxicosis, liver dss hypoglycemia alcohol and opoid withdrawal □ medications nicotine, Caffeine, Corticosteroids Beta- adrenergic agonists SSRI TCA Lithium ▪ parkinsonian gait and other gait patterns ( watch videos downloaded) 71  CNS ▪ secondary motor symptoms ¤ non motor symptoms ▪ neuropsychiatric depression ▪ cognitive ▪ sleep disorders ▪ autonomic dysfunction 72  CNS ▪ sensory abnormalities ♢ diagnosis ¤ is clinical. no current imaging or laboratory tests can be used to confirm this diagnosis with any greater accuracy than history and physical examination ¤ essential criteria bradykinesia + resting tremor or rigidity ¤ exclusion criteria antidopaminergic medication use cerebellar signs (eg, limb ataxia, evoked nystagmus) Vertical (supranuclear) gaze palsy cortical sensory loss (eg, astereognosis) Progressive aphasia ¤ supportive features (OLAA) Olfactory dysfunction excellent response to levodopa asymmetric limb findings (eg, tremor, rigidity) abnormal dopaminergic function on neuroimaging ♢ DDx ¤ essential tremor ¤ secondary parkinsonism ▪ drug induced ( list them ) ▪ stroke, tumor, infection, trauma ¤ atypical parkinsonism ▪ are grp of neurodegenerative conditions that usually are associated with more wide spread neurodegeneration than is found in PD ▪ red flags suggesting atypical parkinsonism absence of resting tremor symmetry of symptoms dementia preceding motor symptoms early speech and gait abnormality early severe dysautonomia early onset hallucination poor response to levodopa ▪ atypical parkinsonism includes ♧ MSA ( multiple system atrophy) suspected when pt presents with atypical parkinsonism in conjunction with early and prominent autonomic dysfunction cerebellar signs ♧ PSP ( progressive supranuclear palsy ) suspected when pts with atypical parkinsonism in conjunction with Vertical gaze palsy, especially downward gaze (mid brain degeneration) 73  CNS progressive aphasia, early onset dementia ( cortical degeneration ) parkinsonian symptoms ( basal ganglia ) cerebellar symptoms ♧ CBD ( corticobasal degeneration ) Alien limb phenomenon (pt perceives the affected limb as not belonging to him Myoclonus, dystonia Cortical sensory loss ♢ trt ( pls look at cathecolamine synthesis and degradation video first ) ¤ levodopa- carbidopa ¤ dopamine agonists ▪ ergot derivatives bromocriptine ( also for trt of hyperprolactenimia, NMS ) cabergoline pergolide ▪ non ergot derivatives ( also for trt of restless leg synd ) pramipexole, ropinirole ¤ COMT inhibitors ▪ entacapone, tolcapone ¤ MAO- B inhibitors ( also for trt of atypical depression) ▪ seligiline, rasagiline ¤ Amantidine ( also for trt of influenza ) ♢ Psychosis (eg, hallucinations, delusions, paranoia) in PD is common and may be due to ¤ underlying disease process, medication, or a combination of the two. ¤ The first step in management of psychosis in PD includes reviewing the patient's medication and considering a cautious dose reduction pts who do not improve with a reduction or who cannot tolerate a 74  CNS dose reduction due to resurgent motor symptoms can be treated with a low-potency, second-generation antipsychotic antipsychotics with more potent dopamine- 2 receptor antagonism (eg, haloperidol, risperidone) should be avoided as these medications have the highest risk of extrapyramidal symptoms and will worsen Parkinson motor symptoms 75  CNS Peripheral neuropathy is acute or chronic damage to peripheral nerves (demyelination and/or axonal degeneration) caused by ♢Idiopathic ♢ Inflammation 1.GBS ¤ amboss ¤ subtypes AIDP ( acute inflammatory demylinating polyneuropathy ) axonal loss ¤ variants miller fisher synd once GBS is suspected the next step in hemodynamically stable pt is assesing the pulmonary function with spirometry ¤ conditions warranting indotracheal intubation a decline in FVC 8 wks can be assymetric and involve both ------------ascending symmetric proximal and distal muscle weakness