Journal of the Neurological Sciences, 1978, 37: 135-143 © Elsevier/North-Holland Biomedical Press
135
CLINICAL FEATURES OF THE GUILLAIN-BARRI~ SYNDROME
DOV SOFFER, SHAUL FELDMAN and MILTON ALTER
Uri Leibowitz Neuroepidemiology Unit (DS, SF), Department of Neurology, Hadassah University Hospital, Jerusalem (Israel) and Department of Neurology ( MA ), Temple University Hospital, Philadelphia, Pa. 19140 (U.S.A.) (Received 18 January, 1978) (Accepted 20 February, 1978)
SUMMARY
In a country-wide search for patients with Guillain-Barrd syndrome (GBS) in Israel, 89 patients were found between 1969 and 1972 who met standardized diagnostic criteria. These cases, derived from a well defined population, were analyzed to provide a more accurate picture of the full range of clinical signs than is available from selected case series in the literature. Preceding illnesses, presenting symptoms, maximal neurological deficit, reflex changes, sensory deficit, cranial nerve, sphincter, respiratory, autonomic disturbances and spinal fluid changes were determined. Mortality was 5.6 which is lower than in many series. Alternatives to account for the apparent benignity of GBS in Israel were offered.
INTRODUCTION
The full range of clinical features of acute infectious polyneuritis (Guillain-Barrd syndrome) remains unclear not only because authorities vary in their definition of the syndrome (Brown and Baker 1947; Haymaker and Kernohan 1949; Boshes and Sherman 1953; Osler and Sidell 1960; Eiben and Gersony 1963; Marshall 1963; Poser and Fowler 1963; Wiederholt, Mulder and Lambert 1964; Leneman 1966; McFarland and Heller 1966; Ravn 1967; Pleasure, Lovelace and Duvoisin 1968) but also because the patients on whom the clinical descriptions are based tend to be selected; for instance, fatal cases (Haymaker and Kernohan 1949), patients from intensive care units (Marshall 1963; Wiener, Meyer and Baumann 1976), age-limited series (Aylett 1954; Low, Schneider and Carter 1958; Peterman, Daly, Dion and Kerth 1959; Dikshit, Taneja and Gupta 1970; Rossi, Mumenthaler, Ltitschg and Ludin 1976) or male patients only (Masucci and Kurtzke 1971). Even series drawn from a single institution (Eiben and Gersony 1963; Wiederholt et al. 1964; McFarland and Heller 1966; Ravn 1967; Eisen
136 and Humphreys 1974; McLeod, Walsh, Prineas and Pollard 1976; LOffel, Rossi, Mumenthaler, Lfitschg and Ludin 1977) may not accurately reflect the full range of clinical features because the institutions may be referral centers for more severe cases by virtue of their special facilities e.g. intensive care units (Eiben and Gersony t963 ; Ravn 1967). A more accurate concept of the full range of clinical features of the GuillainBarr6 syndrome (GBS) can be obtained from a series of well-defined patients collected in a country-wide study. SUBJECTS AND METHODS A country-wide search for GBS was conducted in Israel. Patients were identified by reviewing the National Registry of Neurological Diseases for the period 1969 through 1972. This Registry is based on diagnoses at discharge of all hospitalized patients. As GBS usually causes disability and all segments of the population have ready access to the same high quality medical facilities, including free hospitalization, the likelihood of being included in the Registry was high. All patients accepted for this study fit the following diagnostic criteria: (1) acute or subacute onset of weakness with evolution of signs within two months; (2) bilateral, essentially symmetrical, lower motor neuron type weakness with or without cranial nerve involvement or glove-stocking sensory abnormalities. However, patients with a sensory level on the trunk were excluded; (3) absence of evidence for other diseases known to produce polyneuropathy, e.g. diabetes mellitus, porphyria, collagen disease, infectious mononucleosis, intoxication and neoplasm; (4) less than 100 white blood cells per mm a in spinal fluid. Although albumino-cytologic dissociation is often a criterion of GBS, elevation of protein in spinal fluid was not a requirement for inclusion in the present study. RESULTS The study group consisted of 89 patients who were residents of Israel. Incidence rates and epidemiological features of this series have been reported elsewhere (Softer, Feldman and Alter 1978). The clinical features are the subject of this paper. Preceding illness: An illness during the month preceding onset of GBS occurred in 39 (43.8 %) of the cases (Table 1). Respiratory illness was the most common, accounting for 54 % of those reported. Presenting symptoms: The most frequent presenting symptom was motor weakness. It was reported by 38 patients (42.7 %) (Table 2). Next in frequency were sensory and mixed motor-sensory peripheral complaints. Facial weakness was noted at the onset in 5 cases though it developed later in others (vide infra). One patient reported double vision.
Maximal neurological deficit Motor manifestations: The frequency and severity of motor weakness at the time of maximal involvement is shown in Table 3. Forty-eight patients (53.9 %) displayed
137 TABLE 1 PRECEDING EVENTS IN GBS Type of illness or event
No. of cases
Upper respiratory infection 19 Fever (unexplained) 8 Abdominal pain, vomiting, diarrhea 3 German measles 2 Infectious hepatitis 1 Measles 1 Urinary tract infection 1 Skin eruption 1 Pregnancy, labor 2 Cholecystectomy 1
Total
39
TABLE 2 PRESENTING SYMPTOMS IN GBS Symptom
No. of cases
Motor weakness alone in the legs only in all limbs
34 4
Sensory complaints alone paresthesia paresthesia, legs paresthesia, hands paresthesia, all limbs pain limb pain low back pain
14 3 5 6 11 8 3
Mixed motor-sensory complaints weakness and paresthesia weakness and pain Facial weakness Diplopia Unknown
Total
38
25
16 7 9 5 1 4 89
weakness in all 4 limbs. This i n v o l v e m e n t was severe in 22 cases (24.7 ~ ) . I n 34 p a t i e n t s the weakness was l i m i t e d to the lower extremities. T w o patients h a d n o p e r i p h e r a l weakness t h r o u g h o u t the course o f the disease. I n the l a t t e r patients the disease was c h a r a c t e r i z e d by facial diplegia, loss o f deep t e n d o n reflexes a n d t y p i c a l a l b u m i n o c y tologic d i s s o c i a t i o n in the spinal fluid.
Reflex changes: D e e p t e n d o n reflex a b n o r m a l i t i e s were n o t e d in all 89 patients on w h o m d a t a were available (Table 4). D e e p t e n d o n reflexes were a b s e n t o r r e d u c e d
138 TABLE 3 MOTOR WEAKNESS IN GBS AT TIME OF MAXIMAL INVOLVEMENT Severity of weakness
Part of the body involved lower extremities
upper extremities
Moderate to severe Mild Normal muscle strength Unknown
53 32 2 2
22 26 39 2
Total
89
89
TABLE 4 DEEP T E N D O N R E F L E X CHANGES IN GBS Reflex
No. of cases
Absent, 4 limbs Absent LL, reduced U L Absent LL, normal U L Reduced, 4 limbs Reduced LL, normal UL Not specified
21 16 26 8 8 10
Total
89
LL = lower limbs; UL = upper limbs.
TABLE 5 SENSORY DEFICIT IN GBS AT TIME OF M A X I M A L INVOLVEMENT Type of sensory deficit
Superlicial sensation Dccp sensitivity Normal sensation
Total
Part of the body involved LL (No.)
UL (No.)
21 I1 --
16 3 --
Total (No.)
22 11 56 89
139
TABLE 6 CRANIAL NERVE INVOLVEMENT IN GBS Nerve involved Oculomotor; abducens Facial unilateral bilateral Glossopharyngeal; vagus Accessory Hypoglossal
No. of cases 6 21 6 15 12 1 1
Total
32
in the lower extremities of all cases, but were normal in the upper extremities in 34 patients. Sensory deficit : Neurologic examination disclosed objective sensory deficit in 33 cases (37.0 ~o) (Table 5), although subjective sensory phenomena such as pain and paresthesiae were reported by almost every patient. In most cases the sensory deficit was confined to the distal parts of the extremities often in stocking-glove distribution. Cranial nerve involvement: Cranial nerve dysfunction was present initially in 6.7 ~ and during the entire course it occurred in a total of 32 patients (35.9 ~ ) (Table 6). The facial nerve was most frequently involved, occurring in 21 cases (23.6 ~ ) and was usually bilateral. Sphincter disturbances were noted in 12 patients (13.4~) (Table 7). In 3 cases these disturbances were severe causing urinary and fecal incontinence. In all cases the sphincter dysfunctions were transient and brief. Respiratory and autonomic dysfunction: Fifteen patients (16.8~) had various degrees of respiratory distress. In 7 patients (7.8 ~ ) this was severe enough to necessitate tracheotomy and assisted respiration. Eleven of these 15 patients showed cranial nerve dysfunction in addition. Autonomic dysfunction manifested as hypertension (4 cases), hypotension (1 case) and sinus tachycardia (7 cases). Patients who developed hypertension while on steroid therapy were not included as suffering from autonomic dysfunction. TABLE 7 SPHINCTER DYSFUNCTION IN GBS Type of dysfunction Urinary incontinence Urinary retention Urinary frequency "Difficulty" in micturition Fecal incontinence Constipation Total
No. of cases 3 6 2 1 3 3 12
140 TABLE 8 SEVERITY OF GBS IN C H I L D R E N A N D ADULTS Sign
Adults
Severe quadriparesis (quadriplegia) Cranial nerve dysfunction Sphincter dysfunction Severe respiratory insufficiency Death
%
No.
%
No.
%
17 26 10 6 5
25.0 38.2 14.7 8.8 7.4
5 6 2 1 --
23.8 28.6 9.5 4.8 --
22 32 12 7 5
24.7 36.0 13.5 7.9 5.6
TABLE 9 CSF PROTEIN IN GBS Individual patients All specimens No.
~
50 or less 51-99 100-199 200-499 500-1000 "elevated"
11 18 26 26 4 3
12.5 20.4 29.5 29.5 4.6 3.5
29 35 44 32 5 3
19.6 23.6 29.7 21.6 3.5 2.0
Total
88 a
100.0
148
100.0
No.
a CSF unavailable from 1 patient.
TABLE 10 CSF PLEOCYTOSIS IN GBS Cells/mm8
Individual patients All specimens No.
%
No.
%
9 or less 10-19 20-29 50+
75 6 4 3
85.1 6.8 4.6 3.5
106 7 5 3
87.6 5.8 4.1 2.5
Total
88 •
100.0
121
100.0
a CSF unavailable for 1 patient.
Total
No.
Total: 68 adults, 21 children
CSF protein (mg/100 ml)
Children
141
Mortality: Five patients (5.6 ~) died during the acute phase of the disease. Four of these were 30 years old or over (30, 34, 67 and 80 years old respectively) and one was 16 years old. Severity: The following findings were considered to indicate severe disease: severe quadriparesis or quadriplegia; cranial nerve dysfunction; sphincter disturbances; respiratory insufficiency necessitating assisted respiration; and death. Severe quadriparesis-quadriplegia occurred in 24.7 ~ of the cases, cranial nerve dysfunction in 36.0 ~, severe sphincter disturbances in 13.5 ~o and severe respiratory insufficiency in 7.9 ~. The findings in 21 children and 68 adults are shown in Table 8. Children, in general, had a milder disease than adults, although the difference was not statistically significant. CSFfindings: The CSF was examined in 88 cases. Eleven patients had normal protein levels (Table 9) but most of these patients had only one lumbar puncture. In all other patients an elevated CSF protein was found. The highest level was 1000 mg/100 ml. In 13 patients mild CSF pleocytosis (more than 10 WBC/mm3) was noted. The highest count was 78 cells (Table 10). All the patients with pleocytosis had, in addition, markedly elevated protein. COMMENT The data indicate that in the majority of cases GBS is a relatively benign disease. Serious neurologic manifestations occurred only in the minority of cases. The frequency of severe complication in the Israeli series was lower than in many other reported series which range from 74--94 ~o quadriparesis (Haymaker and Kernohan 1949; Eiben and Gersony 1963; Marshall 1963; Wiederholt et al. 1964; Ravn 1967; McFarland and Heller 1966; Masucci and Kurtzke 1971; McLeod et al. 1976; L6ffel et al. 1977), 72-94 ~ cranial nerve dysfunction (Haymaker and Kernohan 1949; Eiben and Gersony 1963; Marshall 1963; Eisen and Humphreys 1974; Wiener et al. 1976), 24--32~ sphincter disturbances (Haymaker and Kernohan 1949; Eiben and Gersony 1963; Marshall 1963; Ravn 1967; Chhuttani, Chawla, Chugh and Singh 1968; Sheremata, Colby, Lusky et al. 1975) and 18-44 ~ severe respiratory insufficiency (Eiben and Gersony 1963; McFarland and Heller 1966; Ravn 1967; Pleasure et al. 1968; Dikshit et al. 1970; Masucci and Kurtzke 1971; Gashi and Kenrick 1975; McLeod et al. 1976) reaching even 96 ~ in Haymaker and Kernohan's (1949) series. Comparison of mortality rates among different series is more complex. Mortality in GBS is mostly determined by respiratory insufficiency. It is, therefore, not only a function of disease severity, but also reflects the efficacy of respiratory care. Thus it is not surprising that mortality has significantly decreased in recent years with introduction of intensive respiratory care (Ravn 1967; Asbury, Arnason and Adams 1969; Pleasure et al. 1968). Mortality rates in the recent literature vary, but ranged as high as 36.3 ~ (Wiederholt et al. 1964; McFarland and Heller 1966; Pleasure et al. 1968; Dikshit et al. 1970; Masucci and Kurtzke 1971; Lesser, Hauser, Kurland et al. 1973; Goodall, Kosmidis and Geddes 1974; Swick and McQuillen 1976; Rossi et al. 1976; Wiener et al. 1976; L6ffel et al. 1977). It seems, therefore, that the rate of respiratory insufficiency severe enough to
142 necessitate assisted respiration is a better indicator of disease severity than mortality rate. The discrepancy between the Israeli data on disease severity and the data in the literature could be explained in two ways. One possible explanation is that our data represent more accurately the actual spectrum of the disease in the population. Most data in the literature were derived from selected series, and may have had a disproportionately high percentage of severe cases. Another possibility is that the disease affects populations differently, being milder in Israel, for example, and more severe in Europe and North America. That certain segments of the population may show different degrees of severity in GBS has already been proposed by several investigators who noted a milder disease among children with the GBS compared with adults (Peterman et at. 1959; Markland and Riley 1967; Asbury et al. 1969; Paulson 1970; Swick and McQuillen 1976; Lrffel et al. 1977). The same trend was also observed in the present series, although the differences were not statistically significant. It is now generally accepted that GBS is probably a result of cell-mediated hypersensitivity against peripheral myelin, provoked in the majority of cases by certain viral infections (Asbury et al. 1969; Knowles, Currie, Saunders, et al. 1969; Caspary, Currie, Walton et al. 1971 ; Editorial 1975; Sheremata et al. 1975; McLeod et al. 1976). It might be speculated that certain populations or population segments react differently to certain viral antigens making them more susceptible (or resistant) to an autoimmune reaction of the GBS type. It is also possible that the virus strain plays a role in determining disease severity. Certain viruses may be more potent than others in provoking disease or in provoking more severe disease. These viruses may, perhaps, be unevenly distributed geographically, causing more severe disease in certain areas. It should be interesting to see the pattern of disease in clinical studies from different parts of the world, based on cases ascertained from well-defined populations.
REFERENCES Asbury, A. K., B. G. Arnason and R. D. Adams (1969) The inflammatory lesion in idiopathic polyneuritis - - Its role in pathogenesis, Medicine (Baltimore), 48: 173-215. Aylett, P. (1954) Five cases of acute infective polyneuritis (Guillain-Barr6 syndrome) in children, Arch. Dis. Child., 29: 531-536. Boshes, B. and I. C. Sherman (1953) Variability of course of Guillain-Barr6 syndrome, Neurology (Minneap.), 3: 789-799. Brown, J. R. and A. B. Baker (1947) Diagnosis of Guillain-Barrr's disease, .4met. J. Med., 2: 45-52. Caspary, E. A., S. Currie, J. N. Walton et al. (1971) Lymphocyte sensitization to nervous tissues and muscle in patients with the Guillain-Barr6 syndrome, J. NeuroL Neurosurg. Psychiat., 34: 179-181. Chhuttani, P. N., L. S. Chawla, K. S. Chugh and H: Singh (1968) Landry-Guillain-Barr6 Strohl syndrome in India. J. neurol. Sci., 7:581-592. Dikshit, S. K., B. L. V. Taneja and R. C. Gupta (1970) Infectious polyneuritis (GuiUain-Barr6 syndrome) in infancy and childhood, Clin. Med., 77(9) : 22-25. Editorial (1975) Guillain-Barr6 syndrome, Brit. med. J., 3 : 190-191. Eiben, R. M. and W. M. Gersony (1963) Recognition, prognosis and treatment of the Guillain-Barr6 syndrome (Acute idiopathic polyneuritis), Med. Clin. N. Amer., 47:1371-1380. Eisen, A. and P. Humphreys (1974) The Guillain-Barr6 syndrome, Arch. Neurol. (Chic.), 30: 438~43. Gashi, F. and M. M. Kenrick (1975) Guillain-Barr6 syndrome - - Review of the literature, case presentation and physiatric management, Sth. reed. J., 68:1524-1528.
143 Goodali, J. A., J. C. Kosmidis and A. M. Geddes (1974) Effect of corticosteroids on the course of Guillain-Barr6 syndrome, Lancet, 1 : 524-526. Haymaker, W. and J. W. Kernohan (1949) The Landry-Guillain-Barr6 syndrome, Medicine (Baltimore), 28 : 59-141. Knowles, M., S. Currie M. Saunders et al. (1969) Lymphocyte transformation in the GuillainBarr6 syndrome, Lancet, 2: 1168-1170. Leneman, F. (1966) The Guillain-Barr6 syndrome - - Definition, etiology and review of 1,100 cases, Arch. intern. Med., 118: 139-144. Lesser, R. P., W. A. Hauser and L. T, Kurland et al. (1973) Epidemiologic features of the GuillainBarr6 syndrome - - Experience in Olmstead County, Minnesota, 1935 through 1968, Neurology (Minneap.), 23 : 1269-1272. L~Sffel, N. B., L. N. Rossi, M. Mumenthaler, J. Liitschg and H.-P. Ludin (1977) The Landry-GuillainBarr6 syndrome - - Complications, prognosis and natural history in 123 cases, J. neurol. Sci., 33 : 71-79. Low, N. L., J. Schneider and S. Carter (1958) Polyneuritis in children, Pediatrics, 22: 972-990. McFarland, H. R. and G. L. Heller (1966) Guillain-Barr6 disease complex, Arch. Neurol. (Chic.), 14: 196-201. McLeod, J. G., J. C. Walsh, J. W. Prineas and J. D. Pollard (1976) Acute idiopathic polyneuritis, J. neurol. Sci., 27 : 145-162. Markland, L. D. and H. D. Riley (1967) The Guillain-Barr6 syndrome in childhood - - A comprehensive review, including observations on 19 additional cases, Clin. Pediat., 6:162-170. Marshall, J. (1963) The Landry-Guillain-Barr6 syndrome, Brain, 86: 55-66. Mascucci, E. F. and J. F. Kurtzke (1971) Diagnostic criteria for the Guillain-Barr6 syndrome, J. neurol. Sci., 13 : 483-501. Osler, L. D. and A. D. Sidell (1960) The Guillain-Barr6 syndrome - - The need for exact diagnostic criteria, New Engl. J. Med., 262: 964-969. Paulson, G. W. (1970) The Landry-Guillain-Barr6-Strohl syndrome in childhood, Develop. Med. Child NeuroL, 12: 604-607. Peterman, A. F., D. D. Daly, F. R. Dion and H. M. Kerth (1959) Infectious neuronitis (Guillain-Barr6 syndrome) in children, Neurology (Minneap.), 9: 533-539. Pleasure, D. E., R. E. Lovelace and R. C. Duvoisin (1968) The prognosis of acute polyradiculoneuritis, Neurology (Minneap.), 18 : 1143-1148. Poser, C. M. and C. W. Fowler (1963) The nosologic situation of the Landry-Guillain-Barr6 syndrome, Acta neurol, scand., 39: 187-201. Ravn, H. (1967) The Landry-Guillain-Barre syndrome, Acta neurol, scand., Suppl. 30, 43 : 1-64. Rossi, L. N., M. Mumenthaler, J. Ltitschg and H.-P. Ludin (1976) Guillain-Barr6 syndrome in children with special reference to the natural history of 38 personal cases, Neuropildiatrie, 7: 45-51. Sheremata, W., S. Colby, G. Lusky et al. (1975) Cellular hypersensitization to peripheral nervous antigens in the Guillain-Barr6 syndrome, Neurology (Minneap.), 25: 833-839. Softer, D., S. Feldman and M. Alter (1978) Epidemiologic features of the Guillain-Barr6 syndrome, Neurology (Minneap.), Accepted for publication. Statistical Abstract of Israel, 1969-1972, Government Printer, Jerusalem. Swick, H. M. and M. P. McQuillen (1976) The use of steroids in the treatment of idiopathic polyneuritis, Neurology ( Minneap. ) , 26: 205-215. Wiederholt, W. C., D. W. Mulder and E. H. Lambert (1964) The Landry Guillain-Barr6-Strohl syndrome or polyradiculoneuropathy, Proc. Mayo Clin., 39: 427~151. Wiener, S., M. Meyer and P. C. Baumann (1976) Die akute Polyradikulitis, Schweiz. reed. Wschr., 106 : 70-78.
135
CLINICAL FEATURES OF THE GUILLAIN-BARRI~ SYNDROME
DOV SOFFER, SHAUL FELDMAN and MILTON ALTER
Uri Leibowitz Neuroepidemiology Unit (DS, SF), Department of Neurology, Hadassah University Hospital, Jerusalem (Israel) and Department of Neurology ( MA ), Temple University Hospital, Philadelphia, Pa. 19140 (U.S.A.) (Received 18 January, 1978) (Accepted 20 February, 1978)
SUMMARY
In a country-wide search for patients with Guillain-Barrd syndrome (GBS) in Israel, 89 patients were found between 1969 and 1972 who met standardized diagnostic criteria. These cases, derived from a well defined population, were analyzed to provide a more accurate picture of the full range of clinical signs than is available from selected case series in the literature. Preceding illnesses, presenting symptoms, maximal neurological deficit, reflex changes, sensory deficit, cranial nerve, sphincter, respiratory, autonomic disturbances and spinal fluid changes were determined. Mortality was 5.6 which is lower than in many series. Alternatives to account for the apparent benignity of GBS in Israel were offered.
INTRODUCTION
The full range of clinical features of acute infectious polyneuritis (Guillain-Barrd syndrome) remains unclear not only because authorities vary in their definition of the syndrome (Brown and Baker 1947; Haymaker and Kernohan 1949; Boshes and Sherman 1953; Osler and Sidell 1960; Eiben and Gersony 1963; Marshall 1963; Poser and Fowler 1963; Wiederholt, Mulder and Lambert 1964; Leneman 1966; McFarland and Heller 1966; Ravn 1967; Pleasure, Lovelace and Duvoisin 1968) but also because the patients on whom the clinical descriptions are based tend to be selected; for instance, fatal cases (Haymaker and Kernohan 1949), patients from intensive care units (Marshall 1963; Wiener, Meyer and Baumann 1976), age-limited series (Aylett 1954; Low, Schneider and Carter 1958; Peterman, Daly, Dion and Kerth 1959; Dikshit, Taneja and Gupta 1970; Rossi, Mumenthaler, Ltitschg and Ludin 1976) or male patients only (Masucci and Kurtzke 1971). Even series drawn from a single institution (Eiben and Gersony 1963; Wiederholt et al. 1964; McFarland and Heller 1966; Ravn 1967; Eisen
136 and Humphreys 1974; McLeod, Walsh, Prineas and Pollard 1976; LOffel, Rossi, Mumenthaler, Lfitschg and Ludin 1977) may not accurately reflect the full range of clinical features because the institutions may be referral centers for more severe cases by virtue of their special facilities e.g. intensive care units (Eiben and Gersony t963 ; Ravn 1967). A more accurate concept of the full range of clinical features of the GuillainBarr6 syndrome (GBS) can be obtained from a series of well-defined patients collected in a country-wide study. SUBJECTS AND METHODS A country-wide search for GBS was conducted in Israel. Patients were identified by reviewing the National Registry of Neurological Diseases for the period 1969 through 1972. This Registry is based on diagnoses at discharge of all hospitalized patients. As GBS usually causes disability and all segments of the population have ready access to the same high quality medical facilities, including free hospitalization, the likelihood of being included in the Registry was high. All patients accepted for this study fit the following diagnostic criteria: (1) acute or subacute onset of weakness with evolution of signs within two months; (2) bilateral, essentially symmetrical, lower motor neuron type weakness with or without cranial nerve involvement or glove-stocking sensory abnormalities. However, patients with a sensory level on the trunk were excluded; (3) absence of evidence for other diseases known to produce polyneuropathy, e.g. diabetes mellitus, porphyria, collagen disease, infectious mononucleosis, intoxication and neoplasm; (4) less than 100 white blood cells per mm a in spinal fluid. Although albumino-cytologic dissociation is often a criterion of GBS, elevation of protein in spinal fluid was not a requirement for inclusion in the present study. RESULTS The study group consisted of 89 patients who were residents of Israel. Incidence rates and epidemiological features of this series have been reported elsewhere (Softer, Feldman and Alter 1978). The clinical features are the subject of this paper. Preceding illness: An illness during the month preceding onset of GBS occurred in 39 (43.8 %) of the cases (Table 1). Respiratory illness was the most common, accounting for 54 % of those reported. Presenting symptoms: The most frequent presenting symptom was motor weakness. It was reported by 38 patients (42.7 %) (Table 2). Next in frequency were sensory and mixed motor-sensory peripheral complaints. Facial weakness was noted at the onset in 5 cases though it developed later in others (vide infra). One patient reported double vision.
Maximal neurological deficit Motor manifestations: The frequency and severity of motor weakness at the time of maximal involvement is shown in Table 3. Forty-eight patients (53.9 %) displayed
137 TABLE 1 PRECEDING EVENTS IN GBS Type of illness or event
No. of cases
Upper respiratory infection 19 Fever (unexplained) 8 Abdominal pain, vomiting, diarrhea 3 German measles 2 Infectious hepatitis 1 Measles 1 Urinary tract infection 1 Skin eruption 1 Pregnancy, labor 2 Cholecystectomy 1
Total
39
TABLE 2 PRESENTING SYMPTOMS IN GBS Symptom
No. of cases
Motor weakness alone in the legs only in all limbs
34 4
Sensory complaints alone paresthesia paresthesia, legs paresthesia, hands paresthesia, all limbs pain limb pain low back pain
14 3 5 6 11 8 3
Mixed motor-sensory complaints weakness and paresthesia weakness and pain Facial weakness Diplopia Unknown
Total
38
25
16 7 9 5 1 4 89
weakness in all 4 limbs. This i n v o l v e m e n t was severe in 22 cases (24.7 ~ ) . I n 34 p a t i e n t s the weakness was l i m i t e d to the lower extremities. T w o patients h a d n o p e r i p h e r a l weakness t h r o u g h o u t the course o f the disease. I n the l a t t e r patients the disease was c h a r a c t e r i z e d by facial diplegia, loss o f deep t e n d o n reflexes a n d t y p i c a l a l b u m i n o c y tologic d i s s o c i a t i o n in the spinal fluid.
Reflex changes: D e e p t e n d o n reflex a b n o r m a l i t i e s were n o t e d in all 89 patients on w h o m d a t a were available (Table 4). D e e p t e n d o n reflexes were a b s e n t o r r e d u c e d
138 TABLE 3 MOTOR WEAKNESS IN GBS AT TIME OF MAXIMAL INVOLVEMENT Severity of weakness
Part of the body involved lower extremities
upper extremities
Moderate to severe Mild Normal muscle strength Unknown
53 32 2 2
22 26 39 2
Total
89
89
TABLE 4 DEEP T E N D O N R E F L E X CHANGES IN GBS Reflex
No. of cases
Absent, 4 limbs Absent LL, reduced U L Absent LL, normal U L Reduced, 4 limbs Reduced LL, normal UL Not specified
21 16 26 8 8 10
Total
89
LL = lower limbs; UL = upper limbs.
TABLE 5 SENSORY DEFICIT IN GBS AT TIME OF M A X I M A L INVOLVEMENT Type of sensory deficit
Superlicial sensation Dccp sensitivity Normal sensation
Total
Part of the body involved LL (No.)
UL (No.)
21 I1 --
16 3 --
Total (No.)
22 11 56 89
139
TABLE 6 CRANIAL NERVE INVOLVEMENT IN GBS Nerve involved Oculomotor; abducens Facial unilateral bilateral Glossopharyngeal; vagus Accessory Hypoglossal
No. of cases 6 21 6 15 12 1 1
Total
32
in the lower extremities of all cases, but were normal in the upper extremities in 34 patients. Sensory deficit : Neurologic examination disclosed objective sensory deficit in 33 cases (37.0 ~o) (Table 5), although subjective sensory phenomena such as pain and paresthesiae were reported by almost every patient. In most cases the sensory deficit was confined to the distal parts of the extremities often in stocking-glove distribution. Cranial nerve involvement: Cranial nerve dysfunction was present initially in 6.7 ~ and during the entire course it occurred in a total of 32 patients (35.9 ~ ) (Table 6). The facial nerve was most frequently involved, occurring in 21 cases (23.6 ~ ) and was usually bilateral. Sphincter disturbances were noted in 12 patients (13.4~) (Table 7). In 3 cases these disturbances were severe causing urinary and fecal incontinence. In all cases the sphincter dysfunctions were transient and brief. Respiratory and autonomic dysfunction: Fifteen patients (16.8~) had various degrees of respiratory distress. In 7 patients (7.8 ~ ) this was severe enough to necessitate tracheotomy and assisted respiration. Eleven of these 15 patients showed cranial nerve dysfunction in addition. Autonomic dysfunction manifested as hypertension (4 cases), hypotension (1 case) and sinus tachycardia (7 cases). Patients who developed hypertension while on steroid therapy were not included as suffering from autonomic dysfunction. TABLE 7 SPHINCTER DYSFUNCTION IN GBS Type of dysfunction Urinary incontinence Urinary retention Urinary frequency "Difficulty" in micturition Fecal incontinence Constipation Total
No. of cases 3 6 2 1 3 3 12
140 TABLE 8 SEVERITY OF GBS IN C H I L D R E N A N D ADULTS Sign
Adults
Severe quadriparesis (quadriplegia) Cranial nerve dysfunction Sphincter dysfunction Severe respiratory insufficiency Death
%
No.
%
No.
%
17 26 10 6 5
25.0 38.2 14.7 8.8 7.4
5 6 2 1 --
23.8 28.6 9.5 4.8 --
22 32 12 7 5
24.7 36.0 13.5 7.9 5.6
TABLE 9 CSF PROTEIN IN GBS Individual patients All specimens No.
~
50 or less 51-99 100-199 200-499 500-1000 "elevated"
11 18 26 26 4 3
12.5 20.4 29.5 29.5 4.6 3.5
29 35 44 32 5 3
19.6 23.6 29.7 21.6 3.5 2.0
Total
88 a
100.0
148
100.0
No.
a CSF unavailable from 1 patient.
TABLE 10 CSF PLEOCYTOSIS IN GBS Cells/mm8
Individual patients All specimens No.
%
No.
%
9 or less 10-19 20-29 50+
75 6 4 3
85.1 6.8 4.6 3.5
106 7 5 3
87.6 5.8 4.1 2.5
Total
88 •
100.0
121
100.0
a CSF unavailable for 1 patient.
Total
No.
Total: 68 adults, 21 children
CSF protein (mg/100 ml)
Children
141
Mortality: Five patients (5.6 ~) died during the acute phase of the disease. Four of these were 30 years old or over (30, 34, 67 and 80 years old respectively) and one was 16 years old. Severity: The following findings were considered to indicate severe disease: severe quadriparesis or quadriplegia; cranial nerve dysfunction; sphincter disturbances; respiratory insufficiency necessitating assisted respiration; and death. Severe quadriparesis-quadriplegia occurred in 24.7 ~ of the cases, cranial nerve dysfunction in 36.0 ~, severe sphincter disturbances in 13.5 ~o and severe respiratory insufficiency in 7.9 ~. The findings in 21 children and 68 adults are shown in Table 8. Children, in general, had a milder disease than adults, although the difference was not statistically significant. CSFfindings: The CSF was examined in 88 cases. Eleven patients had normal protein levels (Table 9) but most of these patients had only one lumbar puncture. In all other patients an elevated CSF protein was found. The highest level was 1000 mg/100 ml. In 13 patients mild CSF pleocytosis (more than 10 WBC/mm3) was noted. The highest count was 78 cells (Table 10). All the patients with pleocytosis had, in addition, markedly elevated protein. COMMENT The data indicate that in the majority of cases GBS is a relatively benign disease. Serious neurologic manifestations occurred only in the minority of cases. The frequency of severe complication in the Israeli series was lower than in many other reported series which range from 74--94 ~o quadriparesis (Haymaker and Kernohan 1949; Eiben and Gersony 1963; Marshall 1963; Wiederholt et al. 1964; Ravn 1967; McFarland and Heller 1966; Masucci and Kurtzke 1971; McLeod et al. 1976; L6ffel et al. 1977), 72-94 ~ cranial nerve dysfunction (Haymaker and Kernohan 1949; Eiben and Gersony 1963; Marshall 1963; Eisen and Humphreys 1974; Wiener et al. 1976), 24--32~ sphincter disturbances (Haymaker and Kernohan 1949; Eiben and Gersony 1963; Marshall 1963; Ravn 1967; Chhuttani, Chawla, Chugh and Singh 1968; Sheremata, Colby, Lusky et al. 1975) and 18-44 ~ severe respiratory insufficiency (Eiben and Gersony 1963; McFarland and Heller 1966; Ravn 1967; Pleasure et al. 1968; Dikshit et al. 1970; Masucci and Kurtzke 1971; Gashi and Kenrick 1975; McLeod et al. 1976) reaching even 96 ~ in Haymaker and Kernohan's (1949) series. Comparison of mortality rates among different series is more complex. Mortality in GBS is mostly determined by respiratory insufficiency. It is, therefore, not only a function of disease severity, but also reflects the efficacy of respiratory care. Thus it is not surprising that mortality has significantly decreased in recent years with introduction of intensive respiratory care (Ravn 1967; Asbury, Arnason and Adams 1969; Pleasure et al. 1968). Mortality rates in the recent literature vary, but ranged as high as 36.3 ~ (Wiederholt et al. 1964; McFarland and Heller 1966; Pleasure et al. 1968; Dikshit et al. 1970; Masucci and Kurtzke 1971; Lesser, Hauser, Kurland et al. 1973; Goodall, Kosmidis and Geddes 1974; Swick and McQuillen 1976; Rossi et al. 1976; Wiener et al. 1976; L6ffel et al. 1977). It seems, therefore, that the rate of respiratory insufficiency severe enough to
142 necessitate assisted respiration is a better indicator of disease severity than mortality rate. The discrepancy between the Israeli data on disease severity and the data in the literature could be explained in two ways. One possible explanation is that our data represent more accurately the actual spectrum of the disease in the population. Most data in the literature were derived from selected series, and may have had a disproportionately high percentage of severe cases. Another possibility is that the disease affects populations differently, being milder in Israel, for example, and more severe in Europe and North America. That certain segments of the population may show different degrees of severity in GBS has already been proposed by several investigators who noted a milder disease among children with the GBS compared with adults (Peterman et at. 1959; Markland and Riley 1967; Asbury et al. 1969; Paulson 1970; Swick and McQuillen 1976; Lrffel et al. 1977). The same trend was also observed in the present series, although the differences were not statistically significant. It is now generally accepted that GBS is probably a result of cell-mediated hypersensitivity against peripheral myelin, provoked in the majority of cases by certain viral infections (Asbury et al. 1969; Knowles, Currie, Saunders, et al. 1969; Caspary, Currie, Walton et al. 1971 ; Editorial 1975; Sheremata et al. 1975; McLeod et al. 1976). It might be speculated that certain populations or population segments react differently to certain viral antigens making them more susceptible (or resistant) to an autoimmune reaction of the GBS type. It is also possible that the virus strain plays a role in determining disease severity. Certain viruses may be more potent than others in provoking disease or in provoking more severe disease. These viruses may, perhaps, be unevenly distributed geographically, causing more severe disease in certain areas. It should be interesting to see the pattern of disease in clinical studies from different parts of the world, based on cases ascertained from well-defined populations.
REFERENCES Asbury, A. K., B. G. Arnason and R. D. Adams (1969) The inflammatory lesion in idiopathic polyneuritis - - Its role in pathogenesis, Medicine (Baltimore), 48: 173-215. Aylett, P. (1954) Five cases of acute infective polyneuritis (Guillain-Barr6 syndrome) in children, Arch. Dis. Child., 29: 531-536. Boshes, B. and I. C. Sherman (1953) Variability of course of Guillain-Barr6 syndrome, Neurology (Minneap.), 3: 789-799. Brown, J. R. and A. B. Baker (1947) Diagnosis of Guillain-Barrr's disease, .4met. J. Med., 2: 45-52. Caspary, E. A., S. Currie, J. N. Walton et al. (1971) Lymphocyte sensitization to nervous tissues and muscle in patients with the Guillain-Barr6 syndrome, J. NeuroL Neurosurg. Psychiat., 34: 179-181. Chhuttani, P. N., L. S. Chawla, K. S. Chugh and H: Singh (1968) Landry-Guillain-Barr6 Strohl syndrome in India. J. neurol. Sci., 7:581-592. Dikshit, S. K., B. L. V. Taneja and R. C. Gupta (1970) Infectious polyneuritis (GuiUain-Barr6 syndrome) in infancy and childhood, Clin. Med., 77(9) : 22-25. Editorial (1975) Guillain-Barr6 syndrome, Brit. med. J., 3 : 190-191. Eiben, R. M. and W. M. Gersony (1963) Recognition, prognosis and treatment of the Guillain-Barr6 syndrome (Acute idiopathic polyneuritis), Med. Clin. N. Amer., 47:1371-1380. Eisen, A. and P. Humphreys (1974) The Guillain-Barr6 syndrome, Arch. Neurol. (Chic.), 30: 438~43. Gashi, F. and M. M. Kenrick (1975) Guillain-Barr6 syndrome - - Review of the literature, case presentation and physiatric management, Sth. reed. J., 68:1524-1528.
143 Goodali, J. A., J. C. Kosmidis and A. M. Geddes (1974) Effect of corticosteroids on the course of Guillain-Barr6 syndrome, Lancet, 1 : 524-526. Haymaker, W. and J. W. Kernohan (1949) The Landry-Guillain-Barr6 syndrome, Medicine (Baltimore), 28 : 59-141. Knowles, M., S. Currie M. Saunders et al. (1969) Lymphocyte transformation in the GuillainBarr6 syndrome, Lancet, 2: 1168-1170. Leneman, F. (1966) The Guillain-Barr6 syndrome - - Definition, etiology and review of 1,100 cases, Arch. intern. Med., 118: 139-144. Lesser, R. P., W. A. Hauser and L. T, Kurland et al. (1973) Epidemiologic features of the GuillainBarr6 syndrome - - Experience in Olmstead County, Minnesota, 1935 through 1968, Neurology (Minneap.), 23 : 1269-1272. L~Sffel, N. B., L. N. Rossi, M. Mumenthaler, J. Liitschg and H.-P. Ludin (1977) The Landry-GuillainBarr6 syndrome - - Complications, prognosis and natural history in 123 cases, J. neurol. Sci., 33 : 71-79. Low, N. L., J. Schneider and S. Carter (1958) Polyneuritis in children, Pediatrics, 22: 972-990. McFarland, H. R. and G. L. Heller (1966) Guillain-Barr6 disease complex, Arch. Neurol. (Chic.), 14: 196-201. McLeod, J. G., J. C. Walsh, J. W. Prineas and J. D. Pollard (1976) Acute idiopathic polyneuritis, J. neurol. Sci., 27 : 145-162. Markland, L. D. and H. D. Riley (1967) The Guillain-Barr6 syndrome in childhood - - A comprehensive review, including observations on 19 additional cases, Clin. Pediat., 6:162-170. Marshall, J. (1963) The Landry-Guillain-Barr6 syndrome, Brain, 86: 55-66. Mascucci, E. F. and J. F. Kurtzke (1971) Diagnostic criteria for the Guillain-Barr6 syndrome, J. neurol. Sci., 13 : 483-501. Osler, L. D. and A. D. Sidell (1960) The Guillain-Barr6 syndrome - - The need for exact diagnostic criteria, New Engl. J. Med., 262: 964-969. Paulson, G. W. (1970) The Landry-Guillain-Barr6-Strohl syndrome in childhood, Develop. Med. Child NeuroL, 12: 604-607. Peterman, A. F., D. D. Daly, F. R. Dion and H. M. Kerth (1959) Infectious neuronitis (Guillain-Barr6 syndrome) in children, Neurology (Minneap.), 9: 533-539. Pleasure, D. E., R. E. Lovelace and R. C. Duvoisin (1968) The prognosis of acute polyradiculoneuritis, Neurology (Minneap.), 18 : 1143-1148. Poser, C. M. and C. W. Fowler (1963) The nosologic situation of the Landry-Guillain-Barr6 syndrome, Acta neurol, scand., 39: 187-201. Ravn, H. (1967) The Landry-Guillain-Barre syndrome, Acta neurol, scand., Suppl. 30, 43 : 1-64. Rossi, L. N., M. Mumenthaler, J. Ltitschg and H.-P. Ludin (1976) Guillain-Barr6 syndrome in children with special reference to the natural history of 38 personal cases, Neuropildiatrie, 7: 45-51. Sheremata, W., S. Colby, G. Lusky et al. (1975) Cellular hypersensitization to peripheral nervous antigens in the Guillain-Barr6 syndrome, Neurology (Minneap.), 25: 833-839. Softer, D., S. Feldman and M. Alter (1978) Epidemiologic features of the Guillain-Barr6 syndrome, Neurology (Minneap.), Accepted for publication. Statistical Abstract of Israel, 1969-1972, Government Printer, Jerusalem. Swick, H. M. and M. P. McQuillen (1976) The use of steroids in the treatment of idiopathic polyneuritis, Neurology ( Minneap. ) , 26: 205-215. Wiederholt, W. C., D. W. Mulder and E. H. Lambert (1964) The Landry Guillain-Barr6-Strohl syndrome or polyradiculoneuropathy, Proc. Mayo Clin., 39: 427~151. Wiener, S., M. Meyer and P. C. Baumann (1976) Die akute Polyradikulitis, Schweiz. reed. Wschr., 106 : 70-78.
