Guillain-Barre syndrome in Oxfordshire: clinical features in relation to age.
Guillain-Barre syndrome (GBS) has received little attention as a cause of peripheral neuropathy in elderly people. We have recently shown that age-specific incidence rates of GBS in Oxfordshire, UK, increase throughout adult life , and similar findings have been reported from other parts of the world [2-6]. Clinical features in five elderly patients with GBS  have been described, but there are no detailed reports comparing old and young adults.
With the development of effective therapies such as plasma exchange and intravenous immunoglobulin infusion, the clinical features of GBS are under scrutiny [8, 9]. The range of clinical features has been described in geographically-defined populations using standardized diagnostic criteria in Israel , USA , and Australia , but not in the United Kingdom. We have examined the clinical features of GBS and their relation to age in an epidemiologically-based retrospective study of a defined population using standard diagnostic criteria.
Methodological and epidemiological details of this study have been reported previously  Residents of Oxfordshire admitted to hospital with GBS between 1 January 1974 and 31 December 1986 were sought using data from the Oxford record linkage study (ORLS)  as a diagnostic index. Hospital medical records were retrieved. Cases were defined using diagnostic criteria for GBS formulated by the United States National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) , augmented firstly by the inclusion of patients with reduced rather than absent reflexes when accompanied by electrophysiological evidence suggesting demyelinating neuropathy, as in a recent clinical study , and secondly by including patients with the Miller-Fisher syndrome (ophthalmoplegia, ataxia, and areflexia)  without limb weakness, as suggested by Asbury . Patients whose illness took a chronic or relapsing course suggestive of chronic inflammatory polyradiculo-neuropathy  were excluded.
Limb weakness was recorded using the Medical Research Council (MRC) grading system . Significant disability was defined as requiring assistance from another person in one or more simple activities of daily living (as listed in the Barthel Index of activities of daily living  but excluding bathing). To test whether patients over 60 years of age had different clinical characteristics from younger adults (20-59 years), comparisons were made using Fisher's exact test and the [X.sup.2] test with Yates' correction; durations were compared by the Kolmogorov-Smirnov two-sample test .
There were 72 patients, with a mean age at onset of 44.1 years (SD 21.9 range 2-85). Forty (56%) were women, and 32 (44%) were men. Ten (14%) were aged less than 20 years, 41 (57%) were 20-59 years, and 21 (29%) were 60 years and over.
Preceding events: A preceding event or illness was recorded in 47 patients (65%) within 4 weeks of the first symptom of GBS, and 53 patients (74%) within 8 weeks (Table I). More than one event or illness was recorded in three patients. An infective agent was implicated by immunological tests in ten patients: cytomegalovirus (CMV, three patients with upper respiratory symptoms, and one with headache and fever), Epstein-Barr virus (EBV, two patients), influenza (two), varicella (one) and mumps (one).
Table I. Preceding events in 53 patients with GBS Frequency of occurrence 0-4 weeks before 5-8 weeks onset before Upper respiratory infection 31 5 Other respiratory 3 Gastro-intestinal 7 Other infections 4 Trauma or surgery 2(*) 1(*) Pregnant 2([dagger]) Immunization 1 Total (events) 50 6 (*) One patient fell from a horse. Two patients had surgery with general anaesthesia but no blood transfusions (one 8 weeks before GBS onset). ([dagger]) Gestation 28 weeks and 37 weeks at onset of GBS.
Presenting symptoms: Paraesthesiae were reported as presenting symptoms by 30 patients (42%), seven of whom also had weakness, pain, or both at onset (Table II). Twenty-nine patients (40%) had pain, and in 24 (33%) this was the sole presenting symptom. Muscular weakness at presentation occurred in 28 patients (39%), and was the sole symptom in 18 (25%).
Table II. First symptoms in 72 patients with GBS Paraesthesiae Pain Weakness Arms 7 2 3 Legs 8 10 14 Both 14 3 6 Trunk/back 14 Face 1 1 Oculomotor 3 Bulbar 1(*) Neck 1 Total (Patients) 30 29 28 (*) Also had weak legs.
Course of disease: The course of the disease was characterized by progression over several days (median 11, range 1 to 47) to the point of maximal neurological impairment, which was reached within four weeks by 65 patients (90%). The plateau time (between maximal neurological impairment and the first sign of definite recovery) ranged from 0 to 21 days (median 3), with a median duration of disease from onset to the start of recovery of 17 days (257).
Clinical features: The main motor findings recorded at the time of maximal impairment are shown in Table III. Limb weakness was absent in two patients, and confined to the arms in one. Weakness was mainly proximal in 25 patients, and mainly distal in 11. Plantar responses were flexor in 61, absent in nine (of whom three had severe leg weakness), and extensor in two cases (unilaterally in one). Fifteen patients (21%) required mechanical ventilation, for a mean of 28.6 days (range 2-60).
Table III. Neurological signs at maximal neurological impairment in 72 patients with GBS Arms Legs Muscle weakness Absent 14 3 Mild (MRC Grade 4) 25 18 Moderate (MRC Grade 3) 12 21 Severe (Grade 2 or less) 21 30 Tendon reflexes Absent 47 67 Reduced 16 4 Normal 9 1 Increased 0 0 Sensory deficit Absent 41 23 Pin-prick and light touch only 18 12 Vibration and position only 6 21 Both 7 16
Cranial nerves were involved in 25 (35%) patients at first presentation, and in 37 (51%) at the time of maximal neurological deficit. Facial nerve palsy was observed in 35 (49%), and was bilateral in 31. Dysphagia or dysarthria occurred in 18 (25%), and external ophthalmoplegia in 11 (15%). Weakness of trapezius or sternomastoid muscles was noted in three (4%), of the muscles of mastication in two (3%), and of the tongue in one case. Seven patients (10%) were considered to have a combination of features consistent with the Miller-Fisher variant of GBS , accompanied by limb weakness in all except two.
Bilateral papilloedema was seen in two patients, both of whom required ventilation and had bilateral facial nerve palsies, severe quadriparesis, areflexia, extensor planters, and raised CSF protein (1.8 and 2.8 g/l). Sensory signs were present at the time of maximal neurological deficit in 50 patients (69%) (see Table III). An indefinite sensory level on the trunk was noted in five patients (7%).
Autonomic neuropathy affected 25 patients (35%). Seventeen (24%) had abnormal bladder or bowel function, manifesting as urinary retention (9 cases), hesitancy (5), frequency (2), constipation (4) and faecal incontinence (2). Fifteen (8%) had cardiovascular abnormalities: hypertension (6 cases), hypotension (5), sinus tachycardia (6), supraventricular tachycardia (4), and bradycardia (1). Hyponatraemia was observed in two patients, one of whom had a chest infection as the probable cause.
An abnormal mental state was observed during the course of GBS in seven patients (age range 28-85 years). This was present transiently at the onset in one case (mild confusion accompanying severe systemic upset in proven acute CMV infection), and at the point of maximal neurological impairment in two (associated with nocturnal hypoxia in one, and with hyponatraemia in the other). Mental impairment was present throughout the period of disease progression in three patients. One had a history and subsequent course compatible with previously undiagnosed Alzheimer-type dementia, one had confusion accompanying heart failure and systemic upset associated with pre-existing nephrotic syndrome, and the third had mild continuous drowsiness associated with signs of Miller-Fisher syndrome, including marked ataxia. This drowsiness remained unexplained, and resolved at the same time as her other signs.
The cerebrospinal fluid was examined in 71 patients (Table IV), by lumbar puncture carried out between one and 55 days after onset of symptoms (mean 12 days, SD 10.6). In four patients, an initially normal examination was repeated and the first abnormal result is shown. CSF protein was above 0.5 g/l in 59 cases, of whom 56 had fewer than 11 lymphocytes/[mm.sup.3]. None had a normal protein level accompanied by a raised cell count. Nerve conduction studies were carried out in 33 cases. All were abnormal, with a wide variety of findings compatible with polyradiculopathy [20, 21].
Outcome: To compare indices of severity of disease across age-groups, the 21 patients aged 60 years and over were compared with 41 younger adults aged 20-59 years (Table V). None of the patients in this series was treated with plasma exchange. The mean duration of follow-up from the date of onset was 25.5 months (SD 32.51), ranging from 1 to 145 months (median 8.5). Thirty-four patients (47%) were seen at 12 months, of whom 28 were free from significant disability (as defined above). Thirty-eight patients were seen for the last time earlier than 12 months, of whom four died and 34 were free from disability, giving a total of 62 (86%) patients who were known to be alive and free from significant disability at or before 12 months after onset of GBS (10/10 aged 0-19 years, 21/21 aged 20-39, 16/20 aged 40-59, 15/21 aged 60 years and over).
[TABULAR DATA 5 OMITTED]
Four deaths occurred during or within three months of the onset of GBS, a case fatality rate of 6%. Details have been reported previously . One patient (aged 66 years) died of pulmonary embolism 10 days after neurological progression ceased, but before definite recovery was noted. The other three deaths occurred 2-6 weeks after recovery had commenced, and each was associated with significant causes additional to GBS (aged 42 years of cerebrovascular accident, aged 69 years of pneumonia and severe chronic airways obstruction, aged 85 years of heart failure with nephrotic syndrome).
A wide variety of antecedent events has been recorded in case-reports of GBS patients [21, 22]. The association of GBS with preceding respiratory or gastrointestinal infection is well established, and the infective agents most commonly implicated are CMV, EBV, Mycoplasma pneumoniae and Campylobacter jejuni . Associations with surgery  and pregnancy  have been reported in other systematic series, but whether these are more than chance associations remains unproven.
Around a half of all patients report pain as a first symptom. This has generally been attributed to inflammation in dorsal roots and ganglia, but one
study has drawn attention to a possible muscular origin . Mild central nervous system (CNS) involvement such as extensor plantar responses and vague sensory levels occur in up to 10% of patients, and more prominent CNS signs are rare [15, 26]. Papilloedema has been shown in some cases of GBS to be associated with raised intracranial pressure with evidence of decreased reabsorption of cerebrospinal fluid [27, 28].
Our study was prompted partly by observation of an elderly patient in whom confusion was prominent at presentation, but our findings confirm that disturbances of mental function in GBS are usually attributable to accompanying disease or to hypoxia.
The clinical features and course of GBS in our patients were similar to those described in other epidemiologically-based retrospective studies [4, 6, 10], two of which also used the NINCDS criteria [4, 6]. GBS ran an exceptionally mild course in the seven patients over 70 years old in one small series , but no other significant differences in disease severity between adults of different ages have been reported from studies of geographically-defined populations. Associations between poor outcome and age reported in non-epidemiological hospital-based series may result from selection bias [13, 29] .
In our study, the clinical features of GBS were the same in patients 60 years and older as in younger adults (20-59 years), with the exception that cranial nerve involvement was significantly less common in older patients, a finding that could have arisen by chance. Older patients more frequently had accompanying diseases and diagnoses, a non-specific manifestation of the age-associated phenomenon of multiple pathology. More old patients were disabled or dead 12 months after onset, but this difference fell short of conventional statistical significance. There were no other significant differences between old and young adults. This study does not have the power to show small differences, but does exclude large differences between age groups.
The clinical features and outcome of GBS are similar in old and young patients, and this has important implications for the application of conventional therapies such as intensive care and mechanical ventilation, and of newer treatment regimes such as plasma exchange [30, 31] and immunoglobulin infusion .
We thank Dr M. J. Goldacre and Mr A. R. Peecke for assistance and advice and are grateful to consultants in Oxfordshire for permitting access to records of patients under their care.
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Authors' address Division of Geriatric Medicine, Nuffield Department of Clinical Medicine, University of Oxford
Address correspondence to Dr S. J. Winner, Department of Clinical Geratology, The Radcliffe Infirmary, Oxford OX2 6HE
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|Author:||Winner, S.J.; Evans, J. Grimley|
|Publication:||Age and Ageing|
|Date:||May 1, 1993|
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