Guillain - Barre Syndrome - is an acute frequently severe and

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1 12 JAPI march 2013 VOL. 61 Original Article Clinical Profile of Guillain Barre Syndrome Shubhangi Vithal Dhadke 1, Vithal Narayan Dhadke 2, Sachin S Bangar 1, Milind B Korade 3 Abstract Objectives: To study clinical presentation, hospital care and outcome of patients of Guillain Barre Syndrome (GBS) and number of patients of respiratory failure and need for ventilators. To study efficacy of IVIg in patients of GBS. Material and Methods: 40 patients of GBS studied in detail including history, clinical examination and investigations {Nerve conduction velocity and C.S.F. examination}. All patients were watched for respiratory insufficiency and those who developed respiratory paralysis were given assisted mechanical ventilation. Patients were treated with IVIG and outcome was observed. Outcome of 2 groups of patients one treated with IVIg and other not treated with IVIg (supportive line of treatment) were compared. Results: Commonest age group affected was yrs. The male:female ratio was 1.5:1. Antecedent infection in form of fever, cough [11 patients], loose motions [10 patients] were present in 21 out of 40 patients. Quadriparesis was present in 39 patients and paraparesis in 1 patient. Cranial nerve involvement was seen in 25 out of 40 patients. Facial nerve was involved in 12[30%] patients and Glossopharyengeal, vagus nerves were involved in 12[30%] patients. Areflexia was found in all 40 patients. In CSF examination, albuminocytologic dissociation was present in 17 out of 26 patients. NCV findings show conduction velocity slowing, delayed f latencies in 90% patients. Out of 40 patients,13[30%] required mechanical ventilation. Out of 40 patients, 14 were treated with IVIg, 4 patients treated with plasmapheresis and 22 patients received only supportive treatment. Out of 40 patients 30 [75%] patients recovered completely, 8 [20%] patients died and 2 [5%] patients developed severe neurologic deficit. Conclusion: GBS is more common in yrs age group with male:female ratio of 1.5:1. Antecedent infection is seen in 55% patients. Commonest presentation was paresthesia in legs and ascending paralysis. One third [32.5%] patients developed respiratory paralysis and needed ventilatory support. Patients who received IVIg early in the course of disease had faster recovery as compared to patients who received only supportive line of treatment. Introduction Guillain - Barre Syndrome - is an acute frequently severe and type of polyradiculoneuropathy of autoimmune in nature. 1 It is also known as Landry s Paralysis. 2 Guillain - Barre (Ghee-yan-Bah-ray) Syndrome is also known as acute inflammatory demyelinating polyneuropathy (AIDP) and it is an inflammatory disorder of the peripheral nerves. 1 GBS manifests as rapidly evolving areflexic motor paralysis with or without sensory disturbance. The usual pattern is an ascending flaccid paralysis. Weakness typically evolve over hours to a few days and is frequently accompanied by tingling dysaesthesias in the extremities. 6 Autonomic involvement is common. The usual manifestations are loss of vasomotor control with wide fluctuation in blood pressure, postural hypotension and cardiac arrhythmias. Respiratory failure occurred and ventilatory assistance was required in 30% cases. 1,3,5 Aetiology of GBS is not known but about 70% cases were preceded 1 to 3 wks before GBS by acute infectious process, which is usually respiratory or gastrointestinal. The theories suggest an autoimmune mechanism in which the patient s defense system of antibodies and WBC are triggered into damaging the nerve coverings or insulation leading to weakness and abnormal sensation. 1,3,5,6 1 Lecturer in Medicine Department, 2 Head of Department Medicine, 3 Senior Resident, Dept. of Medicine, Dr. V.M. Govt. Medical College, Solapur. Received: ; Revised: ; Re-revised: ; Accepted: To confirm diagnosis nerve conduction velocity (NCV) was performed. These patients NCV show conduction velocity slowing, conduction block, prolonged distal latency. In patients with Axonal form, NCV show reduced compound muscle action potential without conduction velocity slowing. 1,3,5 Treatment part includes supportive care, IVIG and Plasmapheresis. Aims and Objectives 1. To study clinical presentation, Hospital course and outcome in patients of Guillain-Barre syndrome admitted in tertiary care institute. 2. To study the number of patients developing respiratory failure and requiring artificial ventilation. 3. To study the efficacy of Intravenous Immunoglobulin in GBS patients. Material and Methods The present study includes 40 cases of GBS during the period of Jan-2008 to Sep Patients were examined clinically. Investigations were done in the form of Hemogram, Peripheral Smear examination, Renal Function Test including Serum electrolytes in all patients. CSF examination was done for albumino - Cytological dissociation and the diagnosis was confirmed by nerve conduction velocity studies (NCV). All the patients were monitored for respiratory insufficiency and those who developed Respiratory paralysis were treated with mechanical ventilation. Few patients were treated with IVIG, and few with Plasmapheresis. 168 JAPI march 2013 VOL. 61

2 JAPI march 2013 VOL The outcome of two groups of patients, one treated with IVIg and other not treated with IVIg (with supportive line of treatment) was compared. Patient who recovered and discharged were followed up on Out Patients (OPD) basis. The outcome was graded as sequelae. 1. Complete Recovery 2. Minor Sequelae 3. Major Sequelae Bed-ridden Patient and cannot carry out routine activities Inclusion Criterion of GBS Required 1. Progressive weakness of 2 or more limbs due to neuropathy. 2. Areflexia 3. Disease course less than 4 weeks. 4. Exclusion of other causes eg. (a) vasculitis- (polyarteritis nodsa, SLE), (b) toxins (organophosphates, lead) botulism, diphtheria, porphyria) Supportive 1. Relative symmetric weakness. 2. Mild sensory involvement. 3. Facial nerve or other cranial nerve involvement 4. Absence of fever at onset. 5. Typical CSF profile (acellular, increase in protein levels). 6. Electrophysiological evidence of demyelination. Results Table 1 : Age and sex distribution Age Male Female Total More than Total Table 2 : Antecedent events in the patients studied Illness Male Female Total Fever, Cough Loose motions, Vomiting Vaccinations Exanthematous Fever Total Table 3 : Duration between preceding illness and onset of symptoms Onset of weakness Male Female Total 1 Week Week Week Week Months Total Table 4 : Clinical Features Clinical Features Male Female Total Quadriparesis Paraparesis Cranial Involvement Bladder Involvement Sensory Symptom Sensory Signs Atypical presentation (Descending Paralysis) Respiratory Paralysis Fisher Variant Table 5 : Cranial nerve involvement Cranial Nerve Male Female Total Occulomotor Facial-Unilateral Facial-Bilateral Glossopharyngeal, Vagus Spinal Accessory Hypoglossal Total Table 6 : Duration of progression to respiratory paralysis during the course of illness Duration Male Female Total <1 week of onset of weakness weeks More than (>) 2 weeks Table 7 : Various signs encountered in the patients Signs Male Female Total Areflexia Sensory abnormalities Sphincter disturbances Wasting Table 8 : Investigation chart Investigation Abnormal Normal Total CSF Routine Blood Chemistry (BSL, LFT, KFT) NCV Table 9 : Electrophysiological abnormalities (NCV studies) in the patients Parameters No. of patients (40) Percentage Absent/delayed f-wave latencies 36 90% Conduction velocity slowing 36 90% Prolonged distal motor latencies 34 85% Reduced CMAP amplitudes % Absent/reduced SNAPs 28 70% No abnormality 0 0% Absent/Delayed F wave latencies Decreased conduction velocity 34 Prolonged distal motor latencies 35 Reduced CMAP 28 Absent/reduced SNAPs 0 No abnormality Graph representing Electrophysiological Abnormalities in NCV Studies JAPI march 2013 VOL

3 14 JAPI march 2013 VOL. 61 Table 10 : Modalities of treatment and outcome Treatment Total Improved Death Severe Neurodeficit Percentage of Improved Patients IVIG % Plasmapheresis % Supportive % Table 11 : Rapid progression Improved Severe Neurodeficit Death Male Female Total [11] The present study was undertaken during the period of Jan-2008 to Sep The study comprises of 40 patients with Acute Inflammatory Demyelinating Polyneuropathy. There were 24 males and 16 Females (M:F=1:5:1) their ages ranged from 13 yrs to 65 yrs, as given in Table 1. Maximum number of patient i.e. 12 (30%) were between yr. of age group. Next common age group was of years in which 11 (27.5) patients were seen, as evident from table 1. Youngest patients was 13 year old female and oldest was 65 year old female. Table 2 gives antecedent event in patients of GBS studied in which, Twenty two patients (55%) had preceding illness. Majority of the patients i.e. 11(50%) had respiratory infection as evidenced by fever and cough. Gastrointestinal infection was encountered in 10 (45%) patients. One patient had exanthematous fever in the form of measles preceding AIDP with respiratory failure. As is evident from the Table 3, majority i.e. 20 out of 22 (90.90%) patients developed neurologic illness within 4 weeks of antecedent event, while remaining 2 patients developed it between 1-3 months of preceding illness. According to Table 4, the most common clinical feature was observed quadriparesis in 39 (97.5 %) patients. The least common clinical feature observed was paraparesis in 1 (2.5%) patient. Cranial nerves involvement observed in 25 (62.5%) patients, facial nerve was the commonest. Respiratory paralysis occurred in 13 (32.5%) patients. Table 5 indicates involvement of cranial nerves in which commonest cranial nerve involved was facial in 12 [48%] patients. Bilateral Facial nerve involvement was observed in 11 patients. Glossopharyngeal and vagus nerve was involved in 12 [48%] patients, while Hypoglossal and spinal accessory nerve involvement were not seen. Occulomotor nerve involvement was seen in 1 patient. As per Table 6, out of 40 patients, 13(32.5%) had respiratory paralysis during the course of illness. Out of 13 patients 11 [ 84.61%] required respiratory support within one week of onset of weakness. Mean time was 4th day of weakness while only 2 patients required ventilatory support within 1-2 weeks of onset of weakness. As per Table 7, Areflexia is observed in all patients (100%). Wasting particularly of distal muscle was noted in 2(5%) patients at the end of 6 months. According to Table 8, nerve conduction studies were abnormal in 40 patients (100%). Table 9 indicates electrophysiological abnormalities in NCV studies in which, out of 40 patients, 36 (90%) patients had absent / delayed f-wave latencies and slowing of conduction velocity, which was the most common abnormality observed. As per Table 10, out of 40 patients, 22 patients received supportive line of treatment. Out of 22, 15(68.18%) patients improved and 2(5%) patients developed severe neurodeficit at the end of 6 months and 5 patients died. Out of 40 patients, 14 patients received IVIG. Out of 14, 11 (78.57%) patients improved and 3 patients died, 4 patients received Plasmapheresis and all survived (100%). Out of 40 patients, 30 (75%) patients improved and 2(5%) patients developed significant residual neurodeficit at the end of 6 months. 8(20%) patients died due to ventilator associated pneumonia (VAP) and sepsis. All 8 patients were on ventillators. Out of 8 patients, 6 patients age was more than 40 years. Rapid Progression Reaching Maximal Neurodeficit in 7 days. Accordng to Table 11, 11 patients had progression reaching maximal deficit in 7 days. Out of 11, 4 [36.36%] patients improved, 2[ 18.18%] patients had severe neurologic deficit and 5 [45.45%] patients died. So rapid progression reaching maximal neurodeficit in 7 days was the reason of mortality. Discussion Acute Inflammatory Demyelinating Polyneuropathy (AIDP) is the most common form of acute neuromuscular disorder encountered in clinical practice. It is obvious from various studies, that the average incidence of Guillain Barre Syndrome is 0.4 to 1.7 per 1,00,000 population. It is fairly same in so many different geographical areas (Sweden, Italy, UK and U.S.A.) 2 In our study, 40 cases were studied in a span of 2 years hence it is insufficient to predict incidence of GBS from it in this area. Age Prevalence GBS seems to affect all the age groups. However there are studies suggesting some more specific age distribution. Adams, Victor and Ropper have quoted age range from as small as 8 months to as old as 80 years for GBS. Kaplan et al have reported two peaks one between 15 to 35 years and the other between 50 to 75 years of age. 2,3 Jiang - Guoxin in their study in Sweden have observed two peaks one between 20 to 24 years and the other between years. 8 In our study there were maximum 12 patients were in the age group of 31 to 40 years of age. The youngest patient in our study was 13 year old girl and the oldest was 65 years old women. Sex Prevalence Roberto D Alessandro did a study in Emilia-Romagna Italy and found a significant male preponderance in GBS with male: female ratio of In our study there was a male preponderance (26 males out of total 40 case) which confirms to the findings of other studies and 14 case an males with M:F ratio was 1.5:1. History of antecedent events History of antecedent illness is indeed significant in many cases of GBS. According to study done by Winner Hughes et al in more than 50 % of cases there is a significant history of preceding illness. 11 In the our study out of 40 patients twenty two patients (55%) had history of preceding illness. 170 JAPI march 2013 VOL. 61

4 JAPI march 2013 VOL Type of antecedent illness RDM Hadden, RAC Hughes et al have mentioned that two third of the patients of GBS will develop the neurological signs and symptoms within one to two weeks from the antecedent illness. One third of these are form of respiratory infection, One fourth have diarrhoea (usually campylobacter jejuni) and one fourth have influenza like illness. Some other rarer forms of infections mentioned are cytomegalovirus infection, Ebstein Barre Virus, Varicella, HIV infections. Immunization also has been mentioned as one of the rarer triggering factors. 12 In our study the most common preceding illness (11 patients out of 22 patients) was respiratory infection (History of fever and cough). Next was gastrointestinal infection was encountered in ten patients. Duration between preceding illness and onset of weakness Rhode Island study by Gilchrist Craing Woodland, has reported the duration of 1 to 4 weeks between antecedent events and onset of weakness. 13 As is evident from the observation table No.3 in our study, majority i.e. 20 out of 22 patients developed neurological illness within 4 weeks of antecedent event while remaining 2 patients developed between 1 to 3 months. Clinical Features in the GBS Sensory symptoms Loeffel Rossi et al in 1997 reported that in 75% of the patients the first neurological symptoms was paraesthesia in the toes. 14 In our study, before the onset of weakness, sensory symptoms in the form of tingling numbness, paraesthesia or pain were observed in 13 (32.5%) of the patients. 13 Motor symptoms The muscular weakness which is classical of GBS described as ascending and symmetrical with depressed and / or absent Deep Tendon Reflexes (DTRS) this pattern has been described in more than 90 % of cases of GBS in various studies (RDM Hadden and Hughes, Rostani AM et al Brain). 14,15 The weakness is most in the proximal musculature and is accompanied with depressed or absent Deep tendon reflexes in 80% of cases. Adams and Victor have described incidence of absent or depressed reflexes as 90% and in 10% cases there may be preservation of reflexes except ankle jerk which is lost in the initial phase of illness followed by loss of other reflexes later on. Asbury and Cornblath have described motor weakness to be maximum within days and usually the progress of the weakness ceases by 4th to 6th week of onset of illness. 2,14 In our study, out of 40 patients, 39(97.5 %) patients had the most common mode of presentation is ascending paralysis leading to quadriparesis with absent Deep tendon Reflexes. Cranial nerve involvement Loeffel, Rossi et al have quoted 50 % incidence of cranial nerve palsies in GBS in which facial nerve was the commonest. 14 In our study 62.5 % of the patients had cranial nerve involvement, commonest being the facial nerve. Respiratory failure Respiratory failure is the complication of GBS, study done by RDM Hadden, RAC Hughes had 20 % of incidence, while Teitebaum J.S. et al had 10 to 30 % incidence. 16 In our study, the respiratory failure was observed s in 13 (32.5%) patients. At an average, the duration between onset of weakness and respiratory failure is reported to be between 2 to 3 weeks by Hadden and Hughes and Harish Justin et al in their independent studies. In our study, out of 13 patients. 11 had respiratory failure within first week from onset of weakness and 2 patient had it in the second week from the onset of weakness. Duration of mechanical ventilation Ropper A.H. et al studied 38 patients of GBS out of which 19 required ventilation and the mean duration was for 49 days. 17 In our study the longest duration of Ventilation was of 94 days of a 45 year old man. Out of thirteen ventilated patients in this study 11 required it for less than 15 days and one patient required it for more than two months. Laboratory evaluation of GBS Diagnosis of GBS is mainly clinical. Hadden Hughes et al and Winner Hughes et al in their independent studies show that 80 % of the times there is albumino - cytological dissociation in CSF of the patients with GBS 17 In our study out of 26 patients who underwent CSF examination, 17 had albumino-cytological dissociation. Remaining 14 patients could not be subjected to lumbar puncture due to poor general condition and or compromised spontaneous respiration. Nerve conduction velocity is considered as a very useful tool for diagnosis as well as prognostication of AIDP by many authors. 2,3 (Bradley Daraff, Loffel VB et al, John Walten) In our study out of 40 patients, 33 patients had mixed sensorimotor demyelinating neuropathy while 7 patients had pure motor neuropathy so all patients had NCV findings suggestive of GBS. Treatment Good nursing care with Intravenous Immunoglobulins or plasmapheresis is considered as effective mode of treatment of GBS by many studies (Rostani A Metal, Ranfala H et al, RDM Hadden et al) IVIG is considered as treatment of choice in GBS in the dose of 400 mg/kg/day for five days by RDM Hadden et al. 15,18 In our study out of 40 patients, 14 patients received Intravenous immunoglobulin and 4 patients received plasmapheresis while rest of the patients received general nursing care. Plasmapheresis is not available in our hospital. We referred these patients to private hospital, those who were affording. This is the only part of treatment (clinical profile of GBS). This study is too small to find out the efficacy of various treatment modalities. Outcome In general, studies done by various authors worldwide suggest a good clinical outcome from GBS. Hadden and Hughes have reported 6% mortality 15 while GDP Smith et al have quoted a mortality of 4% in their respective studies. 19 In our study out of 40 patients, there were 8 deaths (mortality of 20%). Deaths were due to ventilator associated pneumonia, sepsis, and low amplitude CMAP and patients reporting very late to hospital for admission and age more than 40 years. Neurodeficits James Mcleod et al have quoted 15 to 25% incidence of significant neurodeficit at 6th month of illness. In our study out of 40 patient 2 (5%) patients had significant residual weakness at the end of 6 months. Various Factors that Determine the Outcome Rinske Van Koningsveld, Steyerberg E W studied clinical JAPI march 2013 VOL

5 16 JAPI march 2013 VOL. 61 prognostic scoring system for patients of GBS. 20 They studied 3 variables. Age, preceding diarrhoea, and GBS disability score at 2 weeks after entry, which accurately predicts poor outcome at 6 months. In our study is too small to duplicate such a helpful prognostication method, but we can test the prognostic indicators for accuracy. In our study there were 8 deaths and all of them were treated with mechanical ventilators. So, we can say that age over 40 years and mechanical ventilation are the poor prognostic factors. Severity of the disease course, including length of the ICU and hospital stay, risk of complications and a low amplitude CMAP indicate poor prognosis. Above 40 years of age, 6 patients died. In all 8 dead patients, CMAP was low amplitude. Patients who received Intravenous Immunoglobulin early in the course of disease, had faster recovery. Only 4 patients in our study received plasmapheresis and all were recovered completely. Conclusions 1. Guillain Barre Syndrome is common more in males than females. 2. Commonest age group is between yrs of age, the youngest age is 13 years and the oldest age is 65 years. 3. History of antecedent infection (Gastrointestinal or respiratory) is seen in about 55 % of patients. 4. Commonest presentation of GBS is paresthesia in legs and ascending paralysis. 5. One third (32.5%) of patients developed respiratory paralysis and needed ventilatory support. 6. Nerve Conduction Velocity study is the most useful investigations in diagnosis and abnormal in all GBS patients. 7. Patients who received Intravenous Immunoglobulin, early in the course of disease had faster recovery as compared to patients who received only supportive line of treatment. 8. Facial nerve(bilateral) is commonly involved nerve and all patient had abnormal NCV studies. 9. Areflexia is the most common sign observed in 40 patients. (100%). 10. The most common NCV studies observed is absent / delayed f-wave latencies and slowing of conduction velocity. 11. Out of 40 patients, 32 patients improved. References 1. Hauser SL, Asbury AK. Guillain-Barre Syndrome and other immune-related neuropathies. In Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo D, Jameson JL et al. Harrison s Principles of Internal Medicine. 17th edition,vol-ii. New York: Mc Graw-Hill, 2008; Ropper AH, Brown RH. Adams and Victor s Principles of Neurology. 9th edition.new York: Mc Graw-Hill,2005; Asbury MIC.New Concepts of GBS. J Child Neurology 2000;75: Kliegman RM, Behrman RE, Jenson HB,Staton BF. Guillain Barre syndrome. Nelson Textbook of paediatrics. 18th edition, vol-ii. Philadelphia: Saunders, 2007; Donaghy M. Polyneuropathy.Brain s Diseases of Nervous system.12th Edition.New York: Oxford University press,2009; Ghai OP, Paul VK, Bagga A. Central nervous system. Essential Pediatrics. 7th Edition. New Delhi: CBS publishers and distributors 2009; Hughes RAC, Wijdicks EFM, Benson E, Cornblath DR, Hahn AF, Meythaler JM et al. Supportive care for Patients with Guillain Barre Syndrome Arch Neurol. 2005;62: Guo-Xin J. GBS in Sweden from clinical epidemiology to public health surveillance. Journal of Neurology 1996;75: Ropper AH. Guillain- Barre syndrome variants in Emilia Ramagna, Italy, : Incidence, clinical features, and prognosis. Clinical and Neurology J. Neurol. Neurosurg. Psychiatry 1998;65: Winner SJ, Evans JG. Age Specific Incidence of Guillain Barre Syndrome in Oxfordshire. QJ Med 1990;77: Jacobs BC, van dermeche FGA, Herbrink P, Schmitz PIM, de Klerk MA, van Doorn PA. The spectrum of antecedent infections in Guillain Barre Syndrome case control study. Arch Neurol 1988;45: Seneca H. Influenza; epidemiology, etiology, immunization and management. J Am Geriatrics Soc 1980;28: Louie M, Gilchrist JM, Woodward G. 5 years Rhod Island Hospital Experience GBS. The Lancet Neurology 2000;40: Loffel VB, Rossi LN, Mumenyhaler M. The Landry Gullian Barre Syndrome complication prognosis and natural History of 123 cases. J Neural SG 1977;33: Hadden RDM, Huges RAC. GBS recent advances. Arch Neurol 2008;41: Durand MC, Porcher R, Orlikowski D, Clair CD, Annane D, Jean- Louis Gaillard JL et al. Clinical and electrophysiological predictors of respiratory failure in Guillain-Barre Syndrome: a prospective study. The Lancet Neurology 2006;5: Ropper AH. Electrodiagnostic Abnormalities in 113 Consecutive Patients with Guillain Barre Syndrome Arch Neurol 1990;47: Sater RA, Rostami A. Treatment of Guillain Barre Syndrome with intravenous immunoglobulin. Neurology 1998;51:9-15.y MIC.New Concepts of GBS. J Child Neurology 2000;86: Smith GDP, Hughes RAC. Plasma exchange treatment and prognosis of GBS. Quarterly Journal of Medicine New Series 1985;306: Van Koningsveld R, Steyerberg EW, Hughes RA, Swan AV, Van doorn PA, Jacobs BC. A clinical prognostic scoring system for Guillain-Barre syndrome. Lancet Neurol 2007;6: JAPI march 2013 VOL. 61