---start---- dr vite neuro ok...we are going to finish up what we've been doing - blocks of the NS talking about what goes wrong with lesions in particular areas. we'll finishe up that and then get a chance to apply those - work through cases of localizing CNS and PNS diseases, go over differentials and how to work up clinical cases. should be fun (uh huh.) so, remember - you want to ask three things: is NS disease present (to do that, you have to observe the animal and say is it normal or not, use words to describe what is going on, grade the dysfunction, localize lesion), where is the disease present, and what might be causing the disease. ddx is last, least important thing. saying if disease is there, and where it is, is more important. The hypothalamus - we'll just separate that out of the diencephalon/cerebral hemisphere for a minute. signs may be the same as those of endocrine dz. mostly metabolic diseases - Cushings - functional adrenal tumor or functional pituitary tumor - the pituitary sits right in the middle with the brain like a giant mushroom over it, and when pituitary becomes neoplastic you may see large macroadenomas giving hypothalamic signs including circling, pacing, other diencephalic signs as well as many endocrine dysfunctions, salt/water/sexual/other. Midbrain - small area this is where you start seeing gait abnormalities mentation may be altered may see ataxic, spastic tetraparesis or paralysis reflexes - contralateral hyperreflexia pupillary abnormalities, strabismus decreased sensation caudal to lesion very dilated eye that doesn't respond to light (CN III), along with ataxia, spastic tetraparesis... Pons/Medulla: mentation is altered b/c of part that keeps you awake ataxia, spastic tetraparesis, paralysis ipsilateral deficits in postural ability decreased sensation caudal to lesion ipsilateral hyperreflexia multiple cranial nerve deficits V - XII [see handout. he's rushing] we talked about CN VIII which is auditory... you have outer ear, eardrum, middle ear (hammer, anvil, stapes), round window, inner ear middle ear disease affects CN VII, and maybe causes Horner's syndrome inner ear dz causes CN VIII signs but will be able to hop, will have head tilt, strabismus, nystagmus, off-balance, but good postural ability, replaces knuckling, etc. only other nerve possibly affected is if infxn breaks out into middle ear may see signs of VII dysfunction or horner's syndrome. receptors in inner ear feed up through CN VIII to brainstem - if there was a lesion in lateral vestibular nucleus or sup or med vest nucl would see vestibular signs; if lesion was in the tract might see dysfunction of other nerves as well.this is how you tell central from peripheral vestibular dz. peripheral dz is usually treatable; lesions in the central area are usually tumor or encephalitis with much worse prognosis. we saw a review slide before - remember, with central dz, brainstem dz, you still have loss of balance, head tilt, rolling, nystagmus..with peripheral dz you do not have CN deficits in 5 -12, or cerebellar signs, hemiparesis, etc. slide: brain in section - the bulla are seen below the brain - those are part of middle ear - the inner ear is above the bulla. examples: if you have a lesion in th ebrainstem, on the right side, the postural deficits are on the right side. the head tilt is on the right. the strabismus is in the right eye. the nystagmus has fast phase to the left. there are exceptions to everything. look at this dog with the right sided brainstem lesion: he is sitting with a head tilt to the left; some postural problems - front feet sliding out from under him when he tries to sit. turning to the right when he stands (head tilt to left). walks like he's off-balance, wide spacing of feet, left head tilt body turned to right menace response present in left eye, not in right (can see from right eye though), can blink in right eye. left eye has ventral strabismus nystagmus with fast phase to right side very cute dog corrects knuckling ok on left knuckling deficits on right hops ok to the left hopping deficits to the right. problems: left sided head tilt, ventral strabismus in left eye, nystagmus with fast phase to right (want to put disease on the left, then). if this was central disease, would he have postural deficits? yes. if he had peripheral disease, he would not have postural deficits. so with central dz, should have ipsilateral deficits - but he has contralateral deficits. and has no menace in right eye - recall that when a menace is absent this points to cerebellar lesion on ipsilateral side - so right cerebellar lesion. if there was just a right sided lesion in medulla, everything would fit. but now there is paradoxic vestibular disease b/c of the problem in the tracts going to the cerebellum. a lesion in this area causes head tilt, eye droop, and nystagmus to be on wrong side. b/c of menace missing in right eye and contralateral deficits consider paradoxic vestibular disease. read the notes, they probably make more sense. video: dalmatian - lying on right side with limbs flexed, neck back (opisthotanos). weaves back and forth (like stevie wonder) and has nystagmus. appears off balance which indicates vestibular problem. sways back and forth - bilateral lesion? postural ability - standing on tiptoes. not normal. eyes moving vertically. (fast phase down?). this is central disease. a day later he's looking much better - holds himself sternally. head still weaving and some opisthotonos. not so much on the tippytoes as before. three days later can walk. remember - central vestibular disease mainly neoplastic or inflammatory - those diseases don't usually show such rapid improvement - but this was metronidazole intoxication - 60 mg/kg over a few days can cause these signs. with time and fluids will get better within 2 weeks. Cerebellum: normal mentation with altered, ataxic, dysmetric gait. ipsilateral deficits, menace deficit, intention tremors. remember this dog? saw it last week - alert rottweiller who goosesteps. not normal gait at all. when he runs, he bounces. those are the signs of cerebellar disease. DAMNIT list - degenerative? common. the cerebellum can degenerate so instead of looking like a large shrub covering the brainstem, it is too small. three diseases resulting in malformation of cerebellum during gestation: feline panleukopenia, BVD, hog cholera, bluetongue virus (often on the boards) as well as noninfectious causes. (this isn't degenerative though, is it? it's failure to form correctly, right?) neoplastic disease: this slide shows a large left sided cerebellar tumor that looks necrotic. meningioma of cerebellum. the other thing we see are infections which cause cerebellar signs - infections include the same ones like distemper, toxo, neospora, parasitic, mycotic, FIP, GME, etc. have that list ready when you see progressive central cerebellar signs so you know what to test for. so what's going on with these dogs here? these little puppies are so cute but remember, one of these puppies is quadraparetic, slightly depressed, with spastic quadraparesis, inability to support weight, dysmetria/hypermetria in front legs, worse in hind limbs, appears off balance, falls easily, postural deficits in all limbs, worse in hind limbs, resting nystagmus, whole body tremors. what's his problem? remember quadraparetic, spastic stuff happens with high cord lesions. where else could lesions cause this? higher up in brainstem. what causes postural deficits in all four limbs? PNS disease, cord dz (high), brainstem dz. hmm. nystagmus. what causes that? not PNS. brainstem dz can cause that, or very high cord disease. dysmetria is caused by cerebellar disease. intention tremors also cerebellar. mental dullness is seen with brainstem/higher diencephalon lesions. so brainstem, cerebellum.... but he has full body tremors. what causes that? demyelination in the whole NS. so he probably has a diffuse problem. you can't put it all in one place. if you can't, you probably have diffuse or multifocal NS disease. the puppy has globoid cell leukodystrophy - krabbe dz - causes demyelination in whole NS. will lose reflexes and everything eventually. more on diffuse, multicentric nervous diseases: the thing to know is some things fall off the list quickly - tumors do not act like diffuse diseases; the diseases we see are degenerative, metabolic (thiamine problems, hepatic encephalopathy), toxins, infectious/inflammatory diseases Hepatic encephalopathy: metabolic dysfunction. video: small puppy - dull, uninterested, postural deficits, minimally interested in checking out the roll of tape on the floor, major sign with these is often cerebrocortical dz - dull animals with postural deficits who can walk a little when you push them but who show some mild ataxia when you push them making you think diffuse dz. dx here is usually based on liver function tests, ammonia tolerance test, u/a (ammonium biurate), dye excretion tests, blah blah. tx is to limit toxins going in to liver (change food) for liver in failure, or if the problem is a shunt you try to surgically correct the shunt. but the dog looks no different from a dog who is intoxicated with say ethylene glycol or whatever. ddx must include all those diffuse NS disease causes. video of worse case - cat in right lateral recumbency, nonresponsive, rhythmic jerking, does hiss at other cats, very dull, no postural ability, not able to walk, no cranial nerve deficits but blindness. no righting ability. limbs are flexed, whole body is having flexor spasms (interneuron dishcarge in spinal cord. will eat if you put something in front of its mouth - licks anything, almost pathologically. this is much worse than the dog. this is common to see after shunt surgery. in about 10-15% of cases they start having seizures and then end up like this for 6-8 mos or a year and then after constant nursing may return to normal. no idea why; but starts to occur about 3 days postop. infectious inflammatory disease - hallmarks of rabies are important to know b/c lots of it is around. behavioral changes, paresis, paralysis. here the big concern is raccoon rabies and quite a few rabid cats and some rabid horses; not so many dogs due to vaccination programs. lower motor neuron paresis, paralysis. changes in mentation - nice dog turns aggressive. hind limb paresis can develop in cats, a sign of rabies...abnormal phonation, hanging open mouth, inability to move tongue like with trigeminal neuritis - always ask about rabies vaccine before testing gag reflex. no antemortem rabies test exists. canine distemper virus infection: fairly common around here. this dog has constant repetitive flexor spasms, vomiting, diarrhea, twitching which occurs even when asleep or anesthetized at surgical plane. teeth show enamel hypoplasia, due to infection, some people say this is the hallmark of distemper but we see it with other encephalitides, it's just that this encephalitis is more common. slide: retina, optic disk, vessels coming off. this distemper dog has little circular hyperreflective medallion lesions, bright and shiny, like tin foil, on the retina. other diseases affecting the NS are in notes. testing for distemper isn't so easy. look at clinical signs, signalment (young dog, not vax, runny nose/diarrhea and then seizures), enamel hypoplasia, etc. to confirm can run titers - if high, supportive, but not always high; conjunctival scrapings are easy to do, look for inclusion bodies - strongly supportive. CSF tap with lots of lymphocytes with inclusion bodies strongly supportive as well. inclusions also found in trans epi of bladder, respiratory epithelium. those are common places. also circulating in the blood. other things to remember - never forget the retina - here is a bulla seen on retina, this is FIP, and a protein gel lifting this up from the back of eye. more common - flocculent stuff floating in eye, anterior uveitis - FIP may also cause liver dysfunction, renal dysfunction, very high TP, lack of dehydration; FIP titers not that great for diagnosis. biopsy of liver or kidney may show granulomatous lesions of FIP. before biopsy, your dx is only "suspected FIP" cryptococcus - fungal infection, causes multifocal nervous system dz, also systemic disease - patchy round lesions on retina. can do Ag titer on blood, can culture the retina, (?), can biopsy lesions or do cytology and often see the little areas of budding yeast as in CSF. tx for this is difficult, antifungal tx is difficult, itraconazole and fluconazole are newer and better. cryptococcus is common in dogs here; big problem in AIDS patients. it's a fungus that is very prevalent. GME: this gross specimen of a brain looks like it contains a tumor but this isn't a tumor, it is granulomatous meningoencephalitis which is focal or multifocal and exerts a mass effect b/c it has this very inflamed area - there is a huge infiltrate of mphages, lymphocytes, neutrophils - "sterile" encephalitis b/c we can't find an infectious etiologic agent, bacteria, fungus, etc. on MRI looks like tumor. dx via biopsy. tx with steroids, immunomodulators, radiation, chemotherapy. sometimes can control for years this way before they recur. much more common in dogs than in cats (or people). acts like a mass, no associated organism. the only tumor that acts like multifocal dz is lymphosarcoma, a round cell tumor; malignant histocytosis too (?) little round cell tumors that can affect multiple parts of the brain. two reminders: one is for those who were not here last week he will have office hrs T and Th 5-6 in his office behind pharmacy on 3rd floor; two is any questions on the exam will come from lecture notes. three: after break come back to class to get clinical stuff! ---break--- I'm not supposed to be writing this down, per Dr Glass, but I'm going to write it down anyway if it is interesting enough. this lecture is a review of what we've been taught - some clinical cases and Dr Glass's perspective on gait evaluation which should be similar to that of Vite and Steinberg. Gait evaluation: break into two categories - paresis/paralysis, and ataxia paresis/paralysis: two subcategories: LMN lower motor neuron - short strided, flaccid, bunny hopping; UMN upper motor neuron- spastic, long strided, stiff gait ataxia: three subcategories: cerebellar - dysmetria (abnormality in rate, range, force of movement - stevie wonder movement), vestibular (loss of balance, leaning, looking drunk), GP/UMN (cord ataxia, proprioceptive ataxia) again remember anatomic diagnosis is key esp since we choose ancillary procedures to look at specific areas. three pathways. peripheral to cord, and cord to brain --> ascending proprioceptive pathwasy. upper motor neuron in brain to cord and cord to LMN are the descending motor pathways. third pathway is lower motor neuron system which is from LMN to periphery ascending proprioceptive fibers (SCT) are just lateral to the descending upper motor neuron pathways (RST, MRST) from muscle, you have ascending fibers going to dorsal faniculus (FC, FG - conscious proprioceptive fibers going to contralateral cerebral hemisphere); then you have the spinocerebellar pathway (SCT) going to ipsilateral cerebral hemisphere too. Case one: yellow lab - Bonnie Herbst, from NYC, where she saw three vets. the first told the owners that the dog, who wasn't walking right since purchase at 2-3 mos of age not to worry about it. the second one said don't worry, we'll do hip xrays. the third one said she had hip dysplasia and needed to see an orthopedic surgeon immediately. video of bonnie: head is in ventroflexion, short strided gait in all four limbs. "camped under" - will collapse if walked more than ten feet. never gets back to normal gait. legs never go past shoulders - she doesn't extend. she's 7 mos old and very skinny. her owners are 85 yrs old who got the dog as a gift from their 60 year old kids b/c they wanted a quiet, passive dog who wouldn't run around. quiet here == dull and weak. bonnie has been getting worse. she's now 7 mos old. quality of the weakness is lower motor neuron type. short strided, flaccid, etc. great, he's calling on people by name. would bonnie's reflexes be increased or decreased? decreased is what you expect. this is based on the fact that we see diffuse LMN problem, or diffuse neuromuscular disease. this dog isn't painful. she just has no oomph. she doesn't know she should be able to run around, either. tone is decreased. postural reactions seem ok to me. dogs with diffuse neuromuscular disease are surprisingly able to perform these reactions as long as you support their weight. if you don't, their reactions are slower but it is a support problem, not a proprioceptive problem. reflexes are absent or decreased. so something is affecting lumbosacral intumescence. she has sensory capability but no withdrawal reflex - not enough strength to pull back. very little tone in forelimbs or hindlimbs. raggedy ann doll type. so, anatomic dx: diffuse neuromuscular disease. that means it has something to do with disease in the ventral grey column cell bodies, root, nerve, neuromuscular junction, or muscle. but it's affected in the whole body, whatever it is. ddx: muscle disease: muscular dystrophy (doesn't look like this usually although it could)(good suggestion though, harl.); immune mediated myositis; type II muscle fiber myopathy of labrodor retrievers NMJ disease: myasthenia gravis (the thing here is there are two forms, one in young dogs born with it or getting it shortly after birth - lack of ACH receptors - never reported in labs; or older form where they have ACH receptor Ab and bonnie is too young) but often they rest out of that - and bonnie is always weak, never rests out. Botulism (affects cranial nerves, often hx garbage ingestion, full stomach, more acute than this) nerve: polyradicular neuropathy/coonhound paralysis - usually course is about 8 weeks and gets worse then better but bonnie is chronic, whole life, not better primary motor neuron disease - would expect denervation atrophy but bonny doesn't have that either. Bonnie had EMG in many muscles, many many other tests. muscle biopsy with special staining showed a lack of type II muscle fibers. the good thing is she lives in manhattan and is owned by two old people who want a dog who can just make it outside to pee and poo and then sleep on the couch. bonnie's doing great. loves manhattan. these dogs often stop progressing (getting worse) at about a year and then start looking a bit better. this is an inherited disease. case two: 2 yr old male intact schipperke "skipper" CC: can't walk hx: jumped from owner's arms, now can't walk owner is 6'6", 250 lbs, skipper jumped out of his arms, and he fell 6 feet to the ground. video: 2 days post event - local vet did good workup prior to referral. skipper is dragging the right front leg completely and is tetraparetic. legs are stiff. he can support weight on them when his body is held by someone in the proper position. there is increased tone in all four limbs. postural reactions really bad on right (right arm isn't moving at all), diminished on left but not as bad. severe proprioceptive deficits on right; not so bad on left. patellar reflexes brisk. other reflexes also brisk. difficult to flex limbs. dog doesn't lift head much during this whole thing. when dog fell - owner heard scream, couldn't tell how dog fell, dog couldn't walk. localize lesion - where do you think it is? C1-C6 - high cord lesion. with a lesion like this there is increased tone in all limbs, increased reflexes, neck pain may be present and in fact dog doesn't lift head up. anatomic dx: C1-C6 myelopathy. neck rads from referring vet: look at intervertebral disk, foramen, and articular facets. C5 rostral end is deviated dorsally, impinging the cord. dog has broken neck. what do youdo? medical or surgical management. if you much around in this tiny dog you may do permanent damage and dog may go into respiratory arrest since we're near the phrenic nerve. medical management involves a heavy bandage - cast material dorsally and ventrally and laterally in some areas. be careful. this means STRICT rest for 12 to 16 weeks. so he sent the dog home for rest and monitoring q 4 weeks. (was taking cast off q 2 weeks just to be cleaned, etc) at the next visit - much better - walking on his own, postural deficits not as bad.HOWEVER - dog started running away from him and then tripped and fell - this is a lesson to you - do NOT let the dog run off the leash during your exam. this dog could have REALLY done serious damage to his neck. 8 weeks post fracture - still much better. still changing cast q 2 weeks. still some deficits on the right but doing really well. 16 weeks out - walking pretty much normally however, he radiographed the neck just to see - and the dorsal deviation of C5 is much worse than it was on the first visit. it's still deviated into the canal. however, the cord is pretty resilient if you have a gradual insult. but remember you do not have to surgically repair these fractures all the time. note: local vet who first saw this dog recognized the neck fracture and gave steroids. usually we don't give any steroids after the initial injury so that was it. after he fell in the video they considered giving more but didn't. case three: a fantastic case. Rocky Cavanaugh. he came in last fall. 7 yr old FS labrador with difficulty walking. hx progressive difficulty walking with right side worse. a field trial dog worth a lot of money. has had an MRI from C2-Cd vertebrae. she had steroids at local vet. went to a chiropractor which didn't help, went to neurologist who saw this dog and decided the owner had a lot of money and he would send it for tests so did the MRI from C2 to the caudal vertebrae and the MRI was then sent here.... so Rocky came in. here's his video: bouncy, long stride. some ataxia. some knuckling on right hind. we see that with proprioceptive (cord) ataxia. some pacing - front and hind limbs on same side moving together - abnormal. sometimes legs cross midline. dragging right hind on ground. knuckles on right fore. evidence for unilateral spastic paresis. increased tone (floating up - overreaching). hop to left ok. hop to right much slower, sloppier. hind hops are always slower than fore hops, btw. note: CSF tap was done between making two videos and dog performed better after CSF tap. what's the anatomic diagnosis? scuffing is seen with proprioceptive ataxia. overreaching is typical of spastic paresis/upper motor neuron paresis so, C1-C6 again. (?) but she's already had an MRI of the cord. myelogram: the contrast material in the subarachnoid space is seen - note how it stops cranially? there is a mass at the junction of C1 and the medulla as seen with canine meningioma - they really like the C1-C2 cord segments. we aren't sure why but they do. at surgery, they made an enlargement and scooped out some of the meningioma. told owner dog might take a year to show recurrence and should be retired. four weeks later she got a pheasant :) 8 weeks postop she loks really good - not normal, but good. she injured her cruciate ligament after that hunt and then the owner did retire her but she would cry when he left her at home. still alive, doing great, no signs. not cured forever b/c tumor is still there. case 4: Peanut the pug: 7 month old FS cc: difficulty walking hx: 5 months progressive history of difficulty walking at 2-3 mos of age had car door hit her on head, screamed, ran under the car. sometime after that developed gait abnormality but owner isn't sure if it was before or after that. video of peanut: serious goosestepping. hind limbs are not normal either. long strided in all limbs. scuffing hind limbs. owner asked "does my dog walk abnormally?" and it's hard to respond to that. this dog looks like a member of a Hitler Youth group. this is spastic tetraparesis. limbs are stiff. dog can't tell where limbs are in space. hopping very slow, crossing midline, very abnormal. very bad in hind limb. this isn't subtle at all. the other thing to know about this is that reflexes in all four limbs are brisk. very brisk. anatomic dx: C1-C6 myelopathy what's wrong with this dog? MIND malformation, intoxication, inflammation, infection, injury, neoplasia, degeneration this is a young dog with progressive disease - malformation: hereditary? traumatic? radiograph - skull/cranial neck. there is an abnormal disk space seen. the foramina are all nice and normal but the C1-C2 one is HUGELY abnormal. the apical ligament has ruptured here. the spinous process of C2 isn't over the top of C1 anymore. why has this ruptured? well. the dens is off the ventrorostral aspect of C2 and is held down by the transverse ligament which keeps it from pithing the cord when you bend your neck. this ruptures when you hang a person and that's how you die. the dog here had a disk that ruptured traumatically, and the transverse ligament and apical ligament both ruptured traumatically. so someone went in ventrally and screwed C2 to C1 to stabilize this and keep the dens from pithing the cord. the dog is doing great now. ----end----