Clinical and Neurophysiological Pattern of Guillain-Barré Syndrome in Diabetic and Non Diabetic Patients

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1 Clinical and Neurophysiological Pattern of Guillain-Barré Syndrome in Diabetic and Non Diabetic Patients Shereen Zakarya Department of Neurology, Mansoura University ABSTRACT Objective: To study the clinical and neurophysiological pattern of Guillain-Barré syndrome (GBS) in Diabetics and non diabetic Patients. Materials and Methods: The clinical records of consecutive GBS patients during a 6-year period between 2001 and 2006 were analyzed. 51 cases with GBS, were divided into 2 groups, Group I: 39 non diabetic patients, their ages ranged from years, with a mean age 41±16.8 years, 25 males and 14 females. Patients with other causes of peripheral neuropathy were excluded from the study. Group II: 12 diabetic patients with GBS, 6 males and 6 females, their ages above 50 years, only one female patient was below 20 years. All diabetic patients with past history of diabetic neuropathy were excluded from the study. Results: The majority of the cases presented during the winter months and a preceding infection was reported in two thirds of them. Group I: The pattern of weakness was ascending in 92.3%. Proximal lower limb (LL) weakness was the predominant clinical presentation (89.7%), sensory loss in 59%. Bilateral facial weakness was the commonest cranial nerve affection (64.1%). Autonomic disturbances 26.6%, and need for assisted ventilation in 8 cases (20.5%), nerve conduction studies (NCS) demonstrated a demyelinating pattern in 66.7%, and axonal pattern in 17.9% and no abnormality in 5.1%. 35.9% showed improvement in the 3 rd, the majority of patients (71.8%) improved with one course of intravenous immunoglobulin (IV IG), only 12.8% needed plasma exchange, some factors which indicate bad prognosis include severe autonomic disturbance (12.8%), axonal NCS (17.9%) also it was observed that distal weakness of LL (10.3%) and proximal weakness of UL (17.9%) also indicated bad prognosis. Group II: Ascending progression was reported in (91.7%), distal weakness of both UL (50%) and LL (66.7%) was the predominant clinical presentation, sensory loss was detected in only 33.3%, bilateral facial weakness was also the commonest cranial nerve affection (58.3%), bulbar palsy was detected in only 3.8%, autonomic disturbances in 33.3% which is higher than the detected in non diabetic patients but no one need assisted ventilation, NCS demonstrated also a demyelinating pattern in 66.7%, cerebrospinal fluid (CSF) protein showed mainly mild elevation (the protein was less than 2 gm in 33.3%), 75% improved with one course of IV IG, autonomic and axonal NCS indicate also bad prognosis. Conclusion: The main clinical pattern of weakness in non diabetic GBS patients is proximal weakness of LL, while distal weakness of LL is the main clinical pattern in diabetic GBS, sensory loss is less common in diabetic than in non diabetic patients cerebrospinal fluid (CSF) protein usually showed mild to moderate elevation (less than 2 gm) in diabetic patients, the need for assisted ventilation is less in diabetic patients than non diabetic ones. Autonomic disturbances and axonal type in NCS caused delayed recovery in both diabetic and non diabetic with GBS while predominant distal weakness in the LL and proximal weakness in the UL in non diabetic GBS patients and uncontrolled DM in diabetic GBS patients also caused delayed recovery. (Egypt J. Neurol. Psychiat. Neurosurg., 2008, 45(2): ) INTRODUCTION Guillain-Barré syndrome (GBS) is the most common cause of acute or subacute generalized paralysis. It occurs in all parts of the world and in all seasons affecting children and adults of all ages and both sexes. A mild respiratory or gastrointestinal infection precedes the neuropathic symptoms by 1 to 3 s in about 60 percent of cases 1. GBS is an acute immune mediated polyradiculoneuropathy. GBS is not a disease with variations but a group of syndromes with distinctive subtypes depending upon the site of the immune attack. The major subtypes are acute idiopathic demyelinating polyradiculoneuropathy (AIDP) if the primary target of attack is the myelin sheath, acute motor axonal neuropathy (AMAN) if it involves motor axons at the internodal area, and acute motor Correspondence to Shereen Zakarya, shereenzakarya@yahoo.com. Contact number:

2 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 45 (2) July 2008 sensory axonal neuropathy (AMSAN) if both motor and sensory axons are affected 1. The triad of ataxia, areflexia and ophthalmoplegia, known as Miller Fisher syndrome (MFS), is due to predominant (demyelinating) attack on extraocular motor nerves and proprioceptive sensory fibers. The incidence of these 4 major subtypes differs from region to region with acute idiopathic demyelinating polyradiculoneuropathy predominating in the West, AMAN in China, and MFS in Japan and Taiwan 1,2. All of them are characterized by acute atonic areflexic motor weakness with albumino-cytological dissociation. With the exception of MFS the other subtypes cannot be easily distinguished by clinical features but can be differentiated by electrophysiological characteristics 1. The natural course of the disease is the progression of motor weakness (up to 4 s) that reaches the maximum deficit (nadir) and remains at nadir for several s before improvement starts 3,4. Early introduction (within 2 s of onset) of immunomodulatory therapy can arrest the progression and hasten the recovery. Aim of the present work is to study the clinical and neurophysiological pattern of Guillain-Barré syndrome (GBS) in Diabetic and non diabetic patients. MATERIALS AND METHODS The patients of the present work were admitted to the Neurology Department in IBN Sina Hospital, Kuwait between January 2001 & December They were divided into two groups: Group I: Thirty nine non diabetic patients presented with GBS their diagnosis was based on established clinical criteria of Asbury and Cornblath 5 and was verified by investigations, their ages ranged from 15 to 74 years with a mean 41±16.8, 25 males and 14 females Group II: Twelve diabetic patients satisfied the diagnostic criteria, there were equal numbers of males and females, their ages above 50 years, only one female patient was under the age of 20 years, 9 patients were known to be suffering from diabetes before the onset of motor weakness, the other two patients were detected to be diabetic after admission to the hospital. All the patients files included normal Electromyography (EMG), Nerve Conduction Studies (NCS) before illness i.e. no evidence of peripheral neuropathy before illness. All diabetic patients with past history of diabetic neuropathy before illness were excluded from the study. Both groups were subjected to: 1. History taking 2. Thorough neurological examination was performed at the onset of illness then at regular intervals. 3. The functional status of the patients was assessed using a modified objective scale of Miller published by Ammache et al Laboratory investigations to exclude infectious or metabolic causes of weakness, fasting blood sugar complete blood picture serum urea, creatinine, hepatic function enzymes and erythrocyte sedimentation rate. 5. Cerebrospinal fluid analysis for cells, glucose, and total protein. 6. Electrophysiological studies using standard techniques. The Italian Guillian-Barré study group electrodiagnostic criteria 7, 8 were used to classify the NCS as demyelinating, axonal or mixed type. 7.. Strict control of blood sugar in diabetic patients. 8. Immediately after diagnosis, every patient was given intravenous immunoglobulin (IV IG) 0.4 g/kg body weight for 5 days if the functional grading was more than 2 on Miller's scale. If the weakness persisted over 10 days after the first course of IV IG, a second course of IV IG was given. If the functional grade deteriorated, the patient was subjected to plasma exchange (PE). Statistical Analysis: Frequency, mean, standard deviation and standard error of mean were used to describe data. Chi-square test was used to test for association between groups and clinical categorical data. P value 700

3 was considered significant if less than These tests were run on an IPM compatible personal computer using the statistical package for social scientists (SPSS) for windows 7.5 (SPSS Inc, Chicago, IL, USA). RESULTS This is a retrospective comparative study between Non diabetic GBS patients (Group I) and Diabetic GBS (Group II) Most of the admissions (59%) were during the winter months of November to March. Twenty-seven (69%) patients gave history of preceding illness of which respiratory illness (44%) was the commonest. Of 7 (18%) patients with gastro-intestinal problems, 6 had Diarrhea and 1 nonspecific abdominal pain. No prior illness was reported by 14 (36%) patients. The patients were admitted within I day to a maximum of 21 days after the onset of the illness with an average of 8.3 days. Group I: Thirty nine (39) patients satisfied the diagnostic criteria; 25 males and 14 females with a male to female ratio of 1.8:1. The mean age was 41±16.8 years (range years). The distributions of age and sex are given in table (1). All the 39 patients had motor weakness. In most of them, the weakness started in the lower limbs (LL), then ascended to involve the upper limbs (UL). Combined involvement of both proximal and distal muscle was predominant in the UL, whereas in the LL predominant proximal muscle weakness (89.7%) was noted. The deep tendon reflexes were absent in 36 (92.3%) patients, sluggish in 2 (5.1%) and present in 1 (2.7%) throughout the course of the illness. There were no sensory complaints in 16 (41%) patients at presentation. The patterns of sensory disturbance and motor weakness are given in table (3). The other clinical features like cranial nerve affection, autonomic disturbance and respiratory failure are summarized in table (4). Ophthalmoplegia occurred in 1 GBS patient. Facial weakness was the commonest cranial nerve affection occurring in more than half of the patients. Bulbar weakness was noted in 6 patients (15.4%) and 5 of them developed autonomic disturbance and respiratory failure leading to prolonged ventilatory support and delayed recovery. In addition to these 5 patients, another 3 needed ventilatory support for a few hours and did not have either autonomic disturbance or bulbar palsy. Of the 8 patients requiring ventilatory support, (6 males and 2 females) all of them of different ages. The commonest autonomic disturbance was a combination of labile hypertension and urinary retention. One patient had tachycardia and none developed gastric disturbance or pulmonary edema. All the patients had undergone LP. The CSF protein was normal in 12 patients; the study was performed within 2 s of onset of the illness. The albumino-cytological dissociation was noted in 68%, with CSF protein elevation in 32 patients (Table 5); mean value and highest value g/l; the mean CSF cell count was <1 cell/ µl. All patients had undergone NCS. The most commonly encountered neurophysiological abnormalities were absent or prolonged F wave: 90%, prolonged distal latency: 80%, absent H reflex: 76%, delayed nerve conduction velocity: 73%, partial or complete conduction block: 63%, abnormal blink reflex: 60%, reduced compound muscle action potentials (CMAP): 38% and abnormal sensory nerve action potentials (SNAP): 28%. Demyelination was the predominant type in the neurophysiological work-up followed by axonal type (Table 5). Of the 7 patients with axonal forms, 4 had either absent or low SNAP, which characterizes the AMSAN variant and the other 3 had normal SNAP, typical for the AMAN type. Thirty-nine patients received IV IG. 10 patients was admitted and given IV IG in the first few days of illness onset; IV IG administration was delayed up to the third of admission in other patients because of the atypical progression of their illness. Recovery was accordingly delayed in these patients. Of the 39 patients, 28 (71%) improved with one course of IV IG, 4 (10.3%) required a second course after an interval of 10 days and 5 (12.8%) deteriorated rapidly and required PE. Upon initiation of the treatment, disease progression was arrested, the duration of the plateau phase was shortened and the recovery started in most of the patients (Table 6). In 9 patients, the progression continued up to 4 s, and 4 of them required ventilatory support and PE. Two (5%) patients, in whom the plateau 701

4 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 45 (2) July 2008 phase was prolonged for more than 2 s, showed a delayed recovery. Once the improvement started from nadir, No acute relapses (within 2-3 s of treatment) or mortality were noted in our patients. There was no significant clinical difference between patients with or without prior illness; the admission and initiation of treatment within the first 3 s of illness did not alter the recovery pattern. Patients with predominant distal weakness in the LL, proximal weakness in the UL, autonomic disturbance and axonal type of GBS had a poor outcome (Table 7). Group II: Twelve diabetic patients satisfied the diagnostic criteria, there were equal numbers of males and females, their ages above 50 years, only one patient was under the age of 20 years, 9 patients were known to be suffering from diabetes before the onset of motor weakness, the other two patients were detected to be diabetic after admission to the hospital. All the patient s files included normal EMG, NCS before illness i.e. no evidence of peripheral neuropathy before illness. All diabetic patients with past history of diabetic neuropathy before illness were excluded from the study. Ascending progression was reported in (91.7%), distal weakness of both UL (50%) and LL (66.7%) was the predominant clinical presentation, sensory loss was detected in only 33.3%, bilateral facial weakness was also the commonest cranial nerve affection (58.3%), bulbar palsy was detected in only 3.8%, autonomic disturbances in 33.3% which is higher than the detected in non diabetic patients but no one need assisted ventilation, NCS demonstrated also a demyelinating pattern in 66.7%, CSF protein was normal in 2 patients, 75% showed mainly mild to moderate elevation (CSF protein was less than 2 gm). 9 patients (75%) improved with one course of IV IG, 16.7% needed second course of IV IG and only 8.3% needed plasma exchange. Autonomic, axonal NCS and uncontrolled diabetes mellitus (DM) had a poor outcome. Table 1. Age and sex distribution of non diabetic patients with GBS. Age Male Female Total NO. % NO. % NO. % < > Total Table 2. Age and sex distribution of diabetic patients with GBS. Age Male Female Total NO. % NO. % NO % > Total

5 Age and sex distribution of non diabetic patients with GBS < >70 MALE FEMALE Table 3. Patterns of motor weakness and sensory disturbances in diabetic & non diabetic patients with GBS. Clinical features Evolution of motor weakness Weakness in UL Weakness in LL Sensory loss Signs/pattern Non Diabetic Patients Diabetic Patients NO. % NO. % Ascending Descending Total Proximal > distal Distal > proximal Distal = proximal Total Proximal > distal Distal > proximal Total Paresthesia only Joint position sense only Glove and stocking only All 3 together Any combination of above Total

6 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 45 (2) July 2008 Table 4. Cranial nerve affection, autonomic disturbance and breathing pattern of GBS in diabetic & non diabetic patients. Clinical features Cranial nerve involvement Breathing pattern Autonomic disturbances Signs/pattern Non diabetic Patients Diabetic Patients n % n % Ophthalmoplegia Unilateral facial involvement Bilateral facial involvement No facial involvement Bulbar palsy Total Ventilatory support No ventilatory support Total Labile hypertension alone Retention of urine alone Both together Total Table 5. Laboratory features of the disease in diabetic and non diabetic patients. Investigation CSF Nerve conduction Features Non diabetic Patients Diabetic Patients n % n % No cells Less than 10 cells/µd Protein normal (<0.45 g) Protein g g g >3 g Demyelination type Axonal type Mixed type H reflex abnormality alone Normal

7 Table 6. Treatment and outcome of the disease in both diabetic and non diabetic patients. Outcome Arrest of progression Plateau duration Improvement Treatment Features Non diabetic Patients Diabetic Patients n % n % 1st nd rd th I s >2 s In 2nd In 3rd In 4th In 5th In 6th In 7th In 8th One course of IV IG Two courses of IV IG Plasma exchange Clinical improvement in non diabetic GBS VS diabetic GBS In 2nd In 3rd In 4th In 5th In 6th In 7th In 8th Non diabetic Patients Diabetic Patients 705

8 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 45 (2) July 2008 Table 7. Evaluation of poor prognostic factors in non diabetic patents with GBS. Prognostic factors Patients p n % value Age > 70 years NS Ventilatory support Grade 6 disability in <4 days Plateau duration >14 days CMAP of median nerve < I mv Proximal weakness in UL Distal weakness in LL Severe autonomic disturbance Axonal NCS DISCUSSION GBS is a disease with a worldwide distribution affecting all ages, gender and ethnic groups. Usually, the incidence of GBS increases with age and is more common in persons 50 years or older with a male to female ratio of 1.6:1 6,7-12 compared to 1.8:1 in non diabetic patients in our study, but equal ratio in diabetic patients. As regard age, in non diabetic GBS it occurred in all age groups with predominance above the age of 50 years but in diabetic GBS nearly all the patients were more than 50 years. GBS is a nonseasonal disease 11,14 but seasonal clustering has been reported during summer in Northern China 15, spring in Taiwan 16 and winter and spring (September to March) in many studies 10,13 and in the present study during the winter months of November to March. GBS patients present with a wide clinical spectrum. There are variations in the clinical pattern and differences in immunologic, electrophysiologic and pathologic findings 4. Pattern of weakness is manly proximal in both LL in non diabetic GBS patients but mainly distal in diabetic patients which considered clinical variants of GBS, distal weakness of LL in diabetic patients is difficult to be considered diabetic neuropathy because it is of a acute onset, associated with typical electrophysiological pattern of GBS, also CSF protein was above the normal level. The incidence of AMAN in our population is the same as that in Western countries in contrast to an incidence of 15-20% in Japan, 40% in Latin America and 60-70% in Northern China 1. Western studies indicate a poor recovery for AMSAN and a faster recovery for AMAN 1,17,18,19. Kuwabara et al 20. Reported a variable pattern of recovery (both fast and slow recovery) for AMAN. Both AMSAN and the axonal type showed a delayed recovery pattern in diabetic and non diabetic patients in our study. Our non diabetic patients with predominant distal weakness in LL and proximal weakness in UL had delayed recovery. This type of muscle weakness and recovery pattern were not reported in diabetic patients and most of the other studies. The increase of CSF protein is probably a reflection of the widespread inflammatory disease of the nerve roots but high values have had no clinical or prognostic significance, in less than10% of GBS patients the CSF protein values remain normal throughout the illness 5, in our study CSF protein was normal in 17.9% in non diabetic GBS patients and 16.7% in diabetic GBS patients, CSF protein showed only mild to moderate elevation (less than 2 gm) in diabetic GBS patients but it was reached to high levels in non diabetic GBS patients Bulbar weakness and dysautonomia were considered poor prognostic signs in a Spanish study 12 whereas they were not relevant in a 706

9 Taiwanese study 16. We observed that the development of bulbar weakness was a bad prognostic sign as these non diabetic patients went on to develop autonomic disturbance and respiratory failure needing prolonged ventilatory support. The 8 patients who required ventilatory support and the 5 patients who had a combination of urinary retention and labile hypertension had a prolonged course of their illness. The autonomic disturbances were more common in diabetic patients (33.3%), but no one of them needed ventilatory support. Most of the studies report autonomic disturbance in 66% and ventilatory support in 30% of GBS patients 7,11,12,21 The incidence of autonomic disturbance (25.6% in non diabetic patients and 33.3 in diabetic patients) and requirement for ventilatory support (20% in non diabetic patients) was much lower in our study. Though GBS is a monophasic illness, there are reports of acute and long-term relapses in several studies 8,11,21,22 but we did not observe any acute relapse. Mortality in GBS has decreased from 33 to 5% after the introduction of positive pressure ventilatory support and advanced intensive care management 7,11,23. No deaths were recorded in our study most probably due to the early initiation of treatment. Over the years, treatment of GBS moved from symptomatic to specific immunomodulatory therapy. PE and IV IG are of equal benefit and cost effectiveness 24. We chose IV IG as initial therapy because of its ease of administration. Several controlled clinical trials have shown that both PE and IV IG shorten the time to recovery when used in the early stages of the neuropathy 9. In our study, IV IG was effective up to 3 s after the onset of illness. There are numerous studies about long-term prognostic pointers in GBS 3,7,10,12,20,25,26. Although we concur with most of the commonly mentioned poor prognostic factors, they do not help in the early evaluation (within 2 s) of those patients who are not qualified for treatment at the outset. Hence a need exists for having clinical and electrophysiological pointers to institute early immunomodulatory therapy for the patients with less than grade 2 disability even when the weakness is still in the progressive phase. In some patients there may be late progression after 2 s and a favorable outcome will be denied to them if the treatment is delayed. The non diabetic patients with predominant distal weakness in the LL, proximal weakness in the UL, autonomic disturbance (both hypertension and urinary incontinence together) and those with an axonal type tend to have a delayed recovery but in diabetic patients only autonomic disturbances, axonal type and uncontrolled DM tend to have a delayed recovery but distal weakness of LL didn t indicate poor prognosis. We recommend that patients with any of these factors be given immunomodulatory therapy irrespective of other clinical factors. Since our study population was small especially for diabetic patients, studies with a larger number of patients are needed before making these factors a universal guide to early initiation of treatment. Conclusion The main clinical pattern of weakness in non diabetic GBS patients is proximal weakness of LL, while distal weakness of LL is the main clinical pattern in diabetic GBS, sensory loss is less common in diabetic than in non diabetic patients CSF protein usually showed mild elevation (less than 2 gm) in diabetic patients, the need for assisted ventilation is less in diabetic patients than non diabetic ones. Autonomic disturbances and axonal type in NCS caused delayed recovery in both diabetic and non diabetic patients with GBS while predominant distal weakness in the LL and proximal weakness in the UL in non diabetic GBS patients and uncontrolled DM in diabetic GBS patients also caused delayed recovery. Hence, patients with any of these features should be given immunotherapy early in the course of the disease, In addition to good control of glucose in diabetic patients with GBS. REEFRENCES 1. Asbury AK: New concepts of Guillain-Barre syndrome. J Child Neurol 2000;15: Leone M, Giordana MT. Guillain-Barre` syndrome: A prospective, population- based incidence and outcome survey. Neurology 2003; 60(7): Me Khann GM: Guillain-Barre syndrome clinical and therapeutic observations. Ann Neurol 1990; 27(suppl): S I 3 S

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11 اننمط االكه ن كى وانفس ونوج انعصب نمتالزمة ج الن بار ه ف انمرضى انمصابون وانغ ر مصابون بانبول انسكري