How to cure respiratory infections are severe

over the next several minutes i’m going to discuss very briefly some historicalaspects of guillain-barre syndrome. i will then focus on the clinical features of guillain-barreincluding some of the variance we see in clinical practice. i will talk a bit about the diagnosticapproach to the disorder including consideration of conditions in the differential diagnosisof the presentation. i’ll focus very briefly on the pathogenesis of guillain-barre, andthen spend the rest of the time talking a little bit about the treatment and some prognosticaspects of the disorder. i don’t have any conflicts of interest that are relevant tothis presentation. i would like to take this opportunity to thank dr. elizabeth raynor,my colleague, and dr. ted burns for sharing

some of their slides with me. in 1859 landry first described a case of distalsensory formications and ascending weakness after a prodromal illness with fever, malaiseand pain; and this patient progressed to paralysis over three weeks and died from respiratoryfailure. in addition, he also described four similar cases. sixty years later two frencharmy neurologists, guillain and barre, described an acute neuropathy in two soldiers and theclassic cerebral spinal fluid finding of albuminocytologic dissociation. strohl did the electrodiagnosticstudies in these soldiers, and these authors distinguished the illness from acute paralyticpoliomyelitis. the 1950s and 1960s really saw tremendousresearch into the pathophysiology of the disorder

along two paths. one, to delineate the electrophysiologicfeatures of the disorder and the other along the lines of pathogenesis and immunology.the 1980s and the 1990s were the decades of immunotherapy. guillain-barre syndrome is an acute monophasicimmune-mediated polyradiculoneuropathy with a mean age of onset of about 40 years thataffects slightly more males than females. it affects persons of all ages, races andnationalities. the worldwide incidence of guillain-barre has been reported to be anywherefrom 0.6 to 4 per 100,000 annually. children tend to be affected slightly less frequentlywhereas adults over the age of 50 years have a slightly greater incidence of the disorder.two-thirds of cases of guillain-barre syndrome

are associated with an antecedent infection. the typical clinical presentation of the diseaseis an acute generalized motor greater than senseory syndrome. the official name of thedisorder is “acute inflammation demyelinating polyneuropathy” which emphasizes the timecourse and the pathology of the disease. i will use the term gillain-barre syndrome inthis talk to encompass aidp and all its variance. the most common initial symptom of guillain-barreis paresthesia of the distal extremity, however at this stage, patients have little objectivesensory loss. severe radicular back pain or neuropathic pain affects most cases and iscommonly seen in the whole spectrum of guillain-barre and its variance.

diagnosis of guillain-barre, especially earlyon in children can be difficult and a high index of suspicion is necessary because childrenmay just present with pain, difficulty with walking or even just plain refusal to walk.within a few days, weakness ensues commonly in a symmetric ascending pattern. however,weakness can be somewhat asymmetric especially at the onset of the illness. most patients present initially with proximalas well as distal weakness in the lower extremities that subsequently spreads to the arms. thisis the presentation in approximately half the patients. a third of the patients presentwith both leg and arm weakness, and a few patients, approximately 10-12%, have onsetof weakness in the arms. facial nerve involvement

occurs in 70% of the cases and otopharyngealweakness or bulbar weakness with dysphagia in about 40%. rarely, approximately 5% ofpatients may develop ophthalmoplegia, ptosis, or both, and in this case the differentialdiagnosis of botulism or myasthenia gravis arises. hearing loss, papilledema and vocalchord paralysis are less common. a quarter to a third of the patients go on to developrespiratory failure requiring ventilatory assistance. autonomic dysfunction predominantly in theform of cardiovascular dysregulation is presented in most patients if carefully looked for,but the severity varies quite highly. most often, dysautonomia is in the form of sinustachycardia, but patients may also have bradycardia,

labile blood pressures with hyper and hypotension,or just plain orthostatic hypotension. they may develop cardiac arrhythmias. they maydevelop even neurogenic pulmonary edema and may report changes in sweating. a smallerpercentage of patients, approximately 5% may have dysautonomia that affects the bladderin the form of urinary retention or incontinence or the bowels in the form of constipation,ileus, gastric distention or even fecal incontinence. and in these patients, a differential diagnosisof a spinal cord disorder arises. this table is from the review from dr. alanropper in the “new england journal of medicine” in 1992 and if you look at the top columnor row, paresthesia are frequent initially in approximately 70% of patients, but thesepatients don’t often have sensory impairment.

at the peak of the illness however, both paresthesiaand sensory impairment are seen in the vast majority of patients. weakness involves the legs more than the armsinitially, but at the peak of the illness involves both the arms and the legs in mostpatients. the legs are affected more than the arms in over half of the patients, andapproximately a third of the patients have equal weakness in the legs and the arms. some patients progress rapidly to become ventilator-dependentwithin hours or days, whereas others have mild progression for several weeks and neverlose ambulation. occasional patients may have a stuttering or even a stepwise progression.weakness may range from mild to severe flaccid

quadriplegia; and about a third of the patientsnever lose ambulation. the nadir of the weakness as you see in the picture here is reachedby two weeks in anywhere from 50 to 80% of patients depending on the series. these patientsthen enter a plateau phase, again the duration of the plateau phase varies. the median wasfound to be approximately one week in the large study published in “brain” in 2014that evaluated almost over 500 patients with guillain-barre syndrome. following the plateauphase, patients gradually start to recover there have been diagnostic criteria establishedfor guillain-barre syndrome. the asbury criteria was the initial criteria. more recently wehave the brighton criteria, which provides a level of diagnostic certainty from leveli-iv. however, overall, the features that

are required for the diagnosis include progressiveweakness in more than one extremity associated with areflexia or at least hyporeflexia. some features that strongly support the diagnosisinclude the fact that progressional symptoms occurs for a period of less than four weeks.there’s relative symmetry of motor weakness, although as i mentioned earlier, it may beasymmetric at the onset. sensory symptoms and signs tend to be mild, but we do needto bear in mind the fact that there is a sensory variant of guillain-barre syndrome and i willtalk about that. bilateral facial weakness and autonomic dysfunction when present supportthe diagnosis and the typical cerebrospinal feature of high concentration of protein withthe lack of clear cytosis and typical electrodiagnostic

features, often acquired demyelinating syndrome,further support the diagnosis. having spoken about the typical presentation,let’s focus a little bit on some of the variants that we see in clinical practice.the first variance that was described was miller fisher syndrome and many of you arefamiliar with this presentation of ophthalmoplegia, ataxia, and areflexia without weakness. mostpatients present with at least two of these features and they do have an elevated cerebrospinalfluid protein, and that as many of you are aware, they have the characteristic autoantibodyto ganglioside gq1b. in the western hemisphere, miller fisher syndromeaccounts for approximately 5 to 10% of cases but tends to be most frequent in eastern asia,accounting for up to 25% of cases in japan.

some of these patients may actually progresson to just develop the classic ai dp picture. bickerstaff’s brainstem encephalitis isa variant of miller fisher syndrome and is characterized by alteration in consciousnessthat may progress even on to coma. these patients have paradoxic hyperreflexia rather than areflexia.after initial descriptions of acute inflammatory demyelinating neuropathy, we recognized thatthere were some patients who had axonal features and the acute motor axonal neuropathy variantwas reported in 1993 from northern china. soon after that, acute motor and sensory axonalneuropathy was reported. these cases have also been described from other countries includinghere in the united states. the pharyngeal-cervical brachial variant presentswith ptosis, ophthalmoplegia, bifacial weakness,

pharyngeal or bulbar weakness, neck flexorweakness spreading to the upper extremities. these patients have spared sensation and usuallydon’t have weakness in the lower extremities. and as you can imagine, this really does bringup the differential diagnosis of myasthenia gravis or botulism. the paraparetic variant presents with backpain, bilateral leg weakness, numbness and areflexia that can mimic acute cord lesion.local or restricted variants such as bifacial weakness or bilateral sixth nerve palsieswith paresthesia have also been described. many of us who take care of these patientswill see either a pure sensory ataxic variance or acute pandysautonomia often associatedwith sensory features.

two-thirds of patients report symptoms ofrespiratory or a gastrointestinal tract infection before the onset of the disease and in abouthalf these patients a specific type of infection can be identified. respiratory infectionsare more frequent than gi infections. also, gi infections the vast majority are due tocampylobacter jejuni. mycoplasma is also a bacterial infection that has been implicated.of the viral infections cytomegalovirus is the most common usually associated with therespiratory illness as an antecedent. epstein-barr virus can also be associated. we do see guillain-barresyndrome with associated hiv, usually a seroconversion or an early disease, hepatitis c and of coursenow, zika. a few patients develop guillain-barre syndromeshortly after receiving a vaccine and despite

the fact that these are rare, obviously suchevents cause considerable public concern. even the vaccination campaign against influenzah1n1 in 1976 in the united states approximately 1 in 100,000 persons vaccinated developedguillain-barre syndrome. however, in the 2009 season the incidence was 1 per million thatwas felt to be no different than after any seasonal flu vaccine. a few patients had reportedantecedents of pregnancy, surgery or epidural anesthesia. there are some clinical features that shouldraise red flags to the diagnosis of guillain-barre syndrome. patients who present with severerespiratory involvement with limited limb weakness at the onset usually do not haveguillain-barre syndrome. similarly, severe

sensory signs with limited weakness at onsetis a red flag, although again you have to bear in mind that we may be just dealing witha sensory variant that i alluded to earlier. the bladder and bowel dysfunction in guillain-barrefollows a very specific pattern that one has to be aware of. usually, when patients developbladder and bowel dysfunction they do so at the height of their illness when they havemaximum weakness and that is transient, and usually recovers before limb weakness startsrecovering. so if you see a patient who has severe bladder or bowel dysfunction at theonset of the illness when weakness is not prominent, or if they have persistent bladderor bowel dysfunction during the illness that should raise a red flag to the diagnosis ofguillain-barre.

fever at the onset of illness is not usualbecause they’ve usually gotten over the antecedent infection sorry, and often timesat least when i trained in india and we saw a lot of paralytic poliomyelitis was childrenwho developed a febrile illness and along with the fever developed asymmetric weaknesswith extremely exquisitely painful limbs, usually have paralytic polio and not guillain-barresyndrome. other infections may also be at play here. obviously, a sharp sensory levelshould bring up the diagnosis of myelopathy. and if you have more than 50 lymphocytes percubic millimeter in the cerebrospinal fluid or if there are polymorphonuclear lymphocytesin the cerebrospinal fluid, both of these should bring up other differential diagnosis.

what is the diagnostic evaluation in thesepatients? a careful history and neurological examination is important followed by laboratorytesting, magnetic resonance imaging of the brain or the spine as appropriate, followedby electrodiagnostic studies and lumbar puncture. and i state this in no particular order. the mental side of the examination in thesepatients is usually normal except for the few patients who have brainstem encephalitis.the cranial nerve examination typically reveals normal pupils and that’s an important factorwhen you see patients with a pharyngeal-cervical-brachial variant and you consider a diagnosis of botulism,because botulism often affects the pupils because of dysautonomia. you may see ptosisand ophthalmoparesis, bifacial weakness is

common and of course, bulbar weakness maybe seen in about 40% as i mentioned. the motor examination reveals both proximaland distal weakness, which is largely symmetric and legs are more involved than arms in mostpatients. the brain review that i mentioned earlier reported about 8% of patients witha paraparetic presentation. sensory involvement is in the form of large fiber sensory lossand therefore involves vibration and position sense. the ankle jerks are usually large first.later, most patients develop diffuse areflexia or at least hyperreflexia. in the same series of the brain, approximately10 percent had normal reflexes, despite having weakness in their arms; and 2% despite havingweak legs. and in some of these patients normal

reflexes persisted in the arms later on inthe disease course as well. a small proportion of patients with guillain-barr㩠syndrome,especially the acute motor axonal neuropathy variant, may have preserved or even exaggerateddeep tendon reflexes, as also the patients with bickerstaff’s encephalitis. howeverfor most parts, the presence of exaggerated reflexes should prompt you into consideringacute myelopathies in the differences in diagnosis routine laboratory tests are usually normal.some patients may have mild elevation of serum creatine-kinase, mildly elevated liver enzymesmay be seen. consideration should be given to testing for lyme antibody titers, heavy-metalscreens, toxicology screen, urine porphyrin testing in the relevant clinical context.consideration to hiv testing, again, if there

are risk factors for hiv. please bear in mindthat because the disorder occurs at fetal conversion or early on, the appropriate testto get is a pcr for a viral load and not the antibody testing because they may be antibody-negative.campylobacter jejuni antibodies really offer only prognostic information, and we will talkabout that later. there was a lot of literature about anti-gangliosideantibodies in the ‘80s, maybe the ‘70s and ‘80s and the ‘90s probably. however,usually they do not change management, and they are not ordered in the clinical setting.the exception to this perhaps may be in the second where miller fisher or bickerstaff’sbrainstem encephalitis is suspected when we tend to order gq1b antibodies because of thehigh sensitivity and specificity. but the

fact remains that for the most part, the resultof these antibody testing is not available before we start treatments in these patients cerebrospinal fluid protein elevation withoutclear cytosis, the typical albuminocytologic dissociation, is the hallmark of guillain-barrã©syndrome. however when performed in the first 48 hours, 85% of patients may have normalprotein, about two-thirds had elevated protein in the first week of the illness, and morethan 90 percent do have this pattern in fully developed illness. pleocytosis is unusual. as i mentioned earlier,if you have more than 50 cells per cubic millimeter, several differential diagnoses arise, includingearly hiv infection, lyme disease, leptomeningeal

carcinomatosis, cmv polyradiculitis, sarcoidosis,and other inflammatory or infectious conditions. the absence of albuminocytologic dissociationin the first week does not exclude guillain-barr㩠syndrome, and that’s important to remember. these two boxes are from the same paper anddrain. if you notice in the upper box, normal cell counts of less than five per cubic millimeterwere present in the vast majority of these 500-odd patients. more than 50 cells werenot seen in any of these patients. the lower box looks at protein elevation in the cerebrospinalfluid as a factor of the time between weakness and the lumbar puncture. in the first coupleof days only 50 percent of patients have elevated proteins. by the end of the first week, two-thirdsor more have elevated proteins, but that still

leaves us with the one-third who don’t havethe elevated protein. that’s important to remember. the goals of electrodiagnostic testing inguillain-barr㩠syndrome are to localize abnormalities to the peripheral nerve and to demonstrateevidence of a acquired demyelination. early electrodiagnostic findings may be subtle andrepeat studies may be required if the diagnosis is in doubt. the focus of the study is onnerve conduction testing, rather than needle emg, but both of these are complementary again in that same series from brain 2014,in the first week of illness, approximately 48% of patients had demyelinating featureson nerve conduction studies but 41% had equivocal

nerve conduction studies. i will spend a few minutes talking about thedifferential diagnosis of the disorder. if you think about it, guillain-barr㩠syndromepresents as an acute low motor neuron disorder with weakness and areflexia. so let’s talkabout all of the low motor neuron syndromes, starting from the anterior horn cells andgoing down in the neuroanatomic fashion. acute myelopathy, as we mentioned earlier,are in the differential diagnosis – especially if you have suspicion for a spinal cord level.they may be compressive or non-compressive. and the problem is that in the acute phase,you may have spinal shock and therefore limbs are flaccid, and reflexes are absent and thesetone and reflexes don’t help you distinguish

from an acute myelopathy. in addition to acute myelopathy, focal disordersof the anterior horn cells as part of paralytic poliomyelitis or west nile virus infectionmay cause a low motor neuron type of paralytic presentation. many of these presentationsare thick with evidence for meningitis, fever, et cetera. coming down to the peripheral nerve, criticalillness neuropathy can present with a similar picture, but it’s diagnosed by the companyit keeps. so patients are sick, they are in the icu, they have sepsis, they have multi-organfailure, et cetera. lymphoma or leptomeningeal carcinomatous meningitis often times are associatedwith sensory involvement as well. toxic neuropathy,

solvents, heavy metals – we have thallium.you have arsenic. most of these patients have g.i. symptoms. they have skin manifestations.thallium causes alopecia and [inaudible] manifestations. a brief mention of marine toxins – thesepatients often present with severe paresthesia followed by weakness very rapidly. they canalso have dysautonomia. here i’m talking about tetrodotoxin, which is due to pufferfishingestion or saxitoxin or ciguatoxin. the history is really key here. porphyrias – youknow the presentation with the typical abdominal pain, the photosensitivity, urinary findings,et cetera. vasculitic neuropathy is associated with other features of systemic involvement. we spoke about myasthenia gravis and botulismin the neuromuscular junction. hypermagnesemia

is an infrequent cause of neuromuscular junctionblockage. in children tick paralysis can begin two to four days after the tick bite. it reverseswithin 24 hours after tick removal, and the process here is a motor nerve terminal channelinhibition. coming down to muscle, there are idiopathicinflammatory myopathies that can present quite rapidly sometimes. rarely, but you do seethem. rhabdomyolysis, critical illness myopathy – again, distinguished by the company itkeeps. periodic paralysis or secondary hypokalemia with paralysis, as well as hypophosphatemia. the bottom line however is that early guillain-barrã©syndrome is often the clinical diagnosis. ancillary investigations such as cerebrospinalfluid analysis and electrodiagnostic study

are useful to exclude an alternative diagnosisbut may not help to confirm early guillain-barr㩠syndrome. however, it’s important to diagnosethese patients early because early treatment improves outcome. i’m going to be very brief regarding pathogenesisin the interest of time. it’s presumed autoimmune, but we don’t know exactly what happens.a trivial infection triggers a humoral response and these antibodies cross-react with gangliosidesin the phenomenon of molecular mimicry is. there is complement activation, lymphocytecell infiltration of proximal nerves and nerve roots, and macrophage-mediated myelin strippingcausing segmented demyelination. the pathology of acute motor axonal neuropathy seems tobe slightly different, but i’m not going

to focus on this in the interest of time. what are the clinical pathological correlates?demyelination with conduction failure among motor nerve fibers is what leads to clinicalweakness. demyelination in large diameter sensory fibers leads to distal loss of vibrationand position sense. inflammation of peripheral nerve groups lead to pain, and inflammationof the autonomic ganglia causes dysautonomia. how do we manage these patients? supportivecare and immunotherapy are the two mainstays of their care. most patients with guillain-barrã©syndrome are admitted to the neurologic intensive care unit, or at least to an intermediarycare unit to reduce mortality and morbidity. we need to manage them very carefully andmonitor for respiratory failure, dysautonomia.

nosocomial infection is frequent, usuallypneumonia or urinary tract infections, and one needs to be vigilant to these infectionsand treat them aggressively. deep venous thrombosis and resulting thromboembolism are problemsin these patients who are often immobile and need prophylaxis with compression stockingsand anticoagulants. nutritional support, including nasogastric tube support or even percutaneousendoscopy gastronomy if bulbar paralysis lasts for a significant period is important. siadhcan be associated with guillain-barr㩠syndrome, and needs to be recognized and managed. ifneuropathic pain does not respond to non-[inaudible] agents, other agents – such as gabapentin,pregabalin, carbamazepine, oxcarbazepine, tramadol, et cetera – may need to be used.passive range of movement to prevent contractures,

prevention of decubitus ulcers and preventionof corneal ulcers in patients who have bifacial weakness is important. communication and emotionalsupport cannot be understated because even in patients who are not on the ventilator,this is scary. they get weak very acutely and unable to move. one needs to be able totalk to them about the prognosis, explain to them that they are going to get betterfor the most part. it’s key in patients who are on the ventilator because they’reoften completely conscious. clinical clues to impending respiratory failureinclude weakness of neck flexor muscles. you have them count after they take a deep inspiration,count as fast as possible. that’s called a single breath count. if it’s less than20 or 30 or if they have a poor cough at bedside,

these are signs that they have impending respiratoryfailure. they may also have tachypnea and paradoxical respiration. tachycardia and diaphoresismay also imply respiratory failure, although it may also imply just plain dysautonomia.the monitoring of these patients at the bedside is often performed by forced vital capacitymeasures or measures of maximal inspiratory pressure or maximal expiratory pressure. some of you may be aware of the data fromthe mayo clinic in 2001 that suggested the 20/30/40 rule for intubation and ventilation.if we see less than 20 mls per kilogram, mip less than minus 30 centimeters of water ormep less than 40. the problem with monitoring these is that it’s not easy for patientsto give you adequate effort, and there may

be variation between trials. you have to interpretthese in the clinical context. if the patient looks stable and the numbers look bad, thenyou have to really worry that the numbers may not be reliable. the mip and mep especiallymay be difficult in the presence of bifacial weakness because patients can’t hold onto the tube and give a good feel and blow hard. another reason to intubate these patientsprophylactically is an ineffective cough or an inability to handle secretions i call this the respiratory pyramid. thisis again from the ropper review in nejm. i really like this. the middle of the pyramidshows the vital capacity going from normal all the way down to five mls per kilogram.on the right side, you see the accompanying

respiratory pathophysiology, on the left yousee recommended ventilator management. at about 30 mls per kilogram, poor cough andsecretions start accumulating. just physical therapy is recommended. at about 20, the sighiscompromised, and atelectasis and hypoxia begin. intensive spirometry and deep breathing isnecessary. at about 15 is when patients are usually intubated dysautonomia can cause sudden changes in heartrate and blood pressure or arrhythmia, as i mentioned. it’s important when managingautonomic instability to be extremely conservative and avoid aggressively treating blood pressurefluctuation because patients tend to be very sensitive to medication. if you over treatthe highs, this may exacerbate the lows. for

instance, if you over treat tachycardia orhypertension, it may then result in patients with prolonged hypertension or bradycardia.it’s often best to avoid treating the fluctuations if at all possible. if treatment is necessary,the treatments are usually short acting medications rather than long-acting medications. one otherthing that’s important to bear in mind is to treat aggravating factors. pain can aggravatehypertension or of course tachycardia. hypovolemia can aggravate hypertension, and needs to betreated. the mainstays of immunotherapy – plasmaexchange and intravenous immunoglobulin. plasma exchange was the first treatment proven tobe effective in these patients in two large trials, the north american trial and the frenchtrial. in the interest of time, i will not

go through all the details on this slide butsuffice to say that in both studies plasma exchange performed within two weeks from symptomonset consistently demonstrated a statistically significant reduction in time to weaning fromthe ventilator by 13 to 14 days and in time to walk unaided by 32 to 41 days. in addition,the french cooperative study also demonstrated that the patients who required ventilatoryassistance after entry into the trial were significantly less in the plasma exchangegroup. intravenous immunoglobulin was first demonstratedto be efficacious in guillain-barrã© syndrome by the dutch guillain-barrã© study group twodecades ago. in this study, they compared ivig and plasma exchange. ivig was found tobe actually better than plasma exchange. this

then brought up the question – is it reallytrue that ivig may be better than plasma exchange? however, this slide shows you the north americantrial plasma exchange results and the dutch trial plasma exchange results. you will noticethat the group that received plasma exchange in the dutch trial really did not do as wellas the group that received plasma exchange in the north american trial. it says thatgroup imbalances probably account for this difference between ivig and plasma exchangein the dutch trial. in a subsequent large trial, the plasma exchange sandoglobulin guillain-barrã©trial conclusively showed that there is no real difference between plasma exchange andiv immunoglobulin. i will show you that in a couple of slides.

how do you give intravenous immunoglobulin?the dose is two grams per kilogram. whether to give it over the two days – that’sone gram per kilogram per day; or the same dose over five days, 0.4 grams per kilogramper day for five days – has really not been fully evaluated. there’s some data in childrenthat children who receive the shorter course had more treatment -related fluctuations thanchildren who received the longer course. what do we do with patients in whom we’vetreated them with either plasma exchange or ivig and it’s been 10 to 14 days, and theyare still significantly weak and not getting better? do we then treat them with the othermedication or other modality? if we give them ivig, it doesn’t make sense to give themplasma exchange after that because we are

just going to take away the ivig that we gavethem. if we give them plasma exchange, should we then give them ivig? the study that i mentioned– the plasma exchange and sandoglobulin guillain-barrã© study – looked at this.they randomize patients to three groups – plasma exchange alone, ivig alone, or plasma exchangefollowed by ivig – and conclusively demonstrated that there was really no difference betweengroups, meaning the plasma exchange and ivig were indeed equally efficacious; and plasmaexchange followed by ivig was not indicated. the american academy of neurology practiceguidelines for immunotherapy systematically evaluated all of these studies. the recommendationswere that treatment with plasma exchange or intravenous immunoglobulin hastens recoveryfrom guillain-barrã©. both of them are equally

effective, but plasma exchange may carry agreater risk of side effects and may perhaps be more difficult to administer. i think that’sreally what influences the choice of treatment in the clinical setting. combining the twotreatments is not recommended. i did not really discuss steroids for lack of time, but thisreview and subsequent reviews – including a cochrane interview – also found that steroidsare not beneficial in guillain-barr㩠syndrome. very quickly, plasma exchange requires a largedouble lumen catheter, usually through a central line – although there are centers that canactually do this with a prophylaxis. potential complications include blood pressure instabilityor hypertension. this can be a real problem in patients with severe dysautonomia. infection,pneumothorax, thrombocytopenia or anemia,

prolonged clotting parameters, hypocalcemia,or citrate toxicity are other problems. we usually monitor labs in these patients everyday. if clotting parameters are not optimal, we tend to hold plasma exchange. complications of ivig – infusion reactionsare not infrequent. they are usually managed with pre-medication and also with medicationduring the course of the infusion. the medications include acetaminophen, diphenhydramine, oreven intravenous nasal prednisolone if necessary. infusion reactions are also related to thespeed or the rate of the infusion. it’s important to start the rate slowly and escalategradually. when patients develop reaction, oftentimes dropping the rate helps with thesereactions.

acute renal failure is a rare but seriouscomplication seen in diabetics especially with underlying renal impairment related tothe use of sucrose as a diluent in the ivig. neutropenia and even thrombocytopenia mayoccur. heart failure as a factor of fluid overload may also be an issue. because ofthe hyper viscosity of the molecule, it is a big molecule. in patients who already haveunderlined risk factors of thromboembolism, thromboembolic complications have been described,albeit rarely. iga deficiency is extremely rare in the general population. patients whoreceive ivig can also have a delayed skin reaction with desquamation of the skin. i would like to mention briefly treatment-relatedfluctuations because i often get a call from

my colleagues about this in the clinical setting.approximately 10 percent of patients treated with ivig or plasma exchange deteriorate atleast one grade after initial improvement of stabilization. so they stop progressing,or they even get better but then they deteriorate. this is supposed to be due to a prolongedimmune attack on the nerves. the bottom line – again, not going into great detail. thebottom line is they usually improve after retreatment with the same modality they received.so if they received plasma exchange, a few more exchanges. or if they received ivig,retreatment with ivig – two grams per kilogram for another five days. when they have treatment -related fluctuations,it’s important to consider acute-onset cidp.

cidp is a chronic inflammatory demyelinatingpolyneuropathy and acquired polyneuropathy that can sometimes present very acutely. acutecidp should be considered when patients who are initially diagnosed with guillain-barrã©syndrome had three or more periods of clinical deterioration, or if their deterioration occurseight or more weeks after the disease onset. clinical clues for this is also the fact thatmany of these patients tend to have less severe weakness and maintain the ability to ambulateindependently at the worst of their weakness. they usually don’t have cranial nerve dysfunction.this differentiation is important because treatments are different. there is no real data regarding immunotherapyof variance. the bottom line is you treat

variance similar to treatment of aidp. similarlyin children, the treatments remain similar. prognosis mortality – approximately 5% upto 11% in some series. it’s important to remember that the mean time to complete recoveryis almost 7 months in 80% of cases. most improvement happens within the first year after onset,but can continue after this period, and it’s important to explain this to patients. about65% have minor residual deficits, and 10 to 15 per cent with significant residual deficitsin the form of weakness, fatigue, or pain. some prognostic indicators include older ageat onset of the disease, rapid progression before presentation, ventilator dependency,and preceding infection with cytomegalovirus or campylobacter jejuni.

patients with acute motor axonal neuropathyhave a more delayed recovery usually, but there are some patients who recover fairlyquickly because of the underlying pathophysiology. so it’s important to bear in mind that adiagnosis of acute motor axonal neuropathy does not necessarily mean bad prognosis. there is a very nice online prognostic toolthat is very useful in the clinical setting. this is from the international gps outcomestudy group. there are two of these scores. the egris score is the erasmus gbs respiratoryinsufficiency score. it predicts the probability of respiratory insufficiency within the firstweek of admission. the outcome score on the other hand predicts the probability of walkingindependently at two weeks after hospital

admission. the website is here in red andwhen you go into the website, this is what it looks like. it asks you to agree with theterms of use. you start the tool. it asks you what tool you would like to use. so whatdo you want to predict? do you want to predict risk of respiratory failure in the first weekor inability to walk six months after admission? you pick what you want. you put in your patientdata, and it will give you the score and also the risk in terms of percentage of eitherrespiratory failure or being unable to walk six months after admission.