International Journal of Infectious Diseases 48 (2016) 20–21

Contents lists available at ScienceDirect

International Journal of Infectious Diseases

journal homepage: www.elsevier.com/locate/ijid

Letter to the Editor

Generalized tetanus could be complicated with Guillain–Barré syndrome

A R T I C L E I N F O S U M M A R Y

Keywords: A retrospective analysis of patients diagnosed with tetanus was conducted to evaluate the occurrence of
Tetanus Guillain–Barré syndrome (GBS). Two of 13 tetanus cases were complicated with GBS. Their symptoms
Guillan-Barre syndrome and signs related to GBS improved markedly after a 5-day infusion of intravenous immunoglobulin.
Physicians should keep in mind that GBS can be an important cause of muscle weakness in patients with
tetanus.
ß 2016 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).

1. Introduction 2. Patients

Although its cause is unknown, Guillain–Barré Syndrome (GBS)
is thought to be an autoimmune process triggered by antigenic
stimulation,1 resulting in demyelination and destruction of the
peripheral nerves. There is evidence against an association of GBS
with tetanus toxoid-containing vaccine,2 but the association of
GBS with tetanus is unknown. A retrospective analysis of patients
diagnosed with tetanus who were admitted to Wonkwang
University Hospital in South Korea between January 2000 and
December 2015 was conducted to examine the occurrence of GBS.
During the study period, 13 patients were diagnosed with
generalized tetanus. The mean age of these patients was 63.5
(range 38–79) years, and 62% (8/13) were men. The treatments for
tetanus included metronidazole (100%, 13/13), tetanus immune
globulin (92.3%, 12/13), a benzodiazepine such as midazolam or
diazepam (92.3%, 12/13), muscle relaxants (69.2%, 9/13), and
wound care (61.5%, 8/13). Eleven patients (84.6%) underwent
airway management (six endotracheal intubations and five
tracheostomies). Ten patients (76.9%) were admitted into the

Table 1
Characteristics of tetanus patients with Guillain–Barré syndrome

Case 1 Case 2

Age, years 71 79
Sex Male Female
Type of tetanus Generalized Generalized
Identifiable portal of entry Lower limb Neck
Severity of tetanus Severe Severe
Time from onset of tetanus to GBS (days) 23 8
Duration of ICU stay after onset of GBS (days) 22 6
Previous use of drugs affecting muscle strength Magnesium sulfate, diazepam Vecuronium, midazolam
Symptoms and signs at an early stage of GBS
Muscle strength from MRC grading MRC grade 1 in lower limbs MRC grade 2 in all limbs
Deep tendon reflex Not noticed Diminished
NCS findings 1. Diffuse sensory-motor polyneuropathy 1. Diffuse motor dominant polyneuropathy with
with absent or delayed F waves in the limbs absent F waves in the limbs
2. Mainly demyelinating type with secondary 2. Mainly demyelinating type with secondary
axonopathy axonopathy
3. Delayed terminal latencies in the right phrenic
nerve
Therapeutic option for GBS IVIG for 5 days IVIG for 5 days
Muscle strength after infusion of IVIG MRC grade 4 in lower limbs MRC grade 4 in all limbs

GBS, Guillain–Barré syndrome; ICU, intensive care unit; IVIG, intravenous immunoglobulin; MRC, Medical Research Council; NCS, nerve conduction study.

http://dx.doi.org/10.1016/j.ijid.2016.04.011
1201-9712/ß 2016 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 Letter to the Editor / International Journal of Infectious Diseases 48 (2016) 20–21
intensive care unit (ICU) and received mechanical ventilation (for a
range of 3–30 days). One patient (7.7%) died of tetanus. One or
more complications of tetanus were observed in 11 patients
(84.6%): 10 patients (76.9%) with autonomic dysfunction, eight
(61.5%) with hospital-acquired infections (eight pneumonia, three
wound infections, and three Clostridium difficile infections), and
one (7.7%) with deep vein thrombosis.
During the study period, two cases (15.4%) were complicated
with GBS. Before they were diagnosed with GBS, one patient
received midazolam and vecuronium, and the other patient
received diazepam and magnesium sulfate. Despite discontinuing
these drugs based on the improvement in the tetanus, the patients
had muscle weakness of the limbs and abnormal deep tendon
reflex responses. The results of nerve conduction studies (NCS)
were strongly suggestive of GBS. For both patients, their symptoms
and NCS findings fulfilled the requirements for level 2 of the
Brighton criteria for GBS.3 Because sampling of cerebrospinal fluid
had not been performed, cytoalbuminological dissociations could
not be confirmed. The GBS occurred 23 days after the onset of
tetanus in one patient (case 1) and 8 days after onset in the other
patient (case 2). After a 5-day infusion of intravenous immuno-
globulin, muscle strength improved in both patients, from Medical
Research Council (MRC) grade 1 to MRC grade 4 or higher (Table 1).
3. Discussion
The patients with tetanus investigated in this study received
diverse drugs including sedatives, muscle relaxants, and magne-
sium sulfate to relieve the tetanus-related symptoms, and these
could lead to generalized muscle weakness. A tracheostomy was
performed in some patients with tetanus, and these patients were
admitted to the ICU for mechanical ventilation.4 It is well known
that a substantial number of patients admitted to the ICU will
develop ICU-acquired weakness (ICUAW).5 In the present study,
when a physician detected muscle weakness in a patient, the
physician surmised that the muscle weakness may have resulted
from the drugs prescribed or ICUAW. However, in some cases,
muscle weakness continued after these drugs were discontinued,
and the patients were finally diagnosed with GBS based on the
symptoms and the results of NCS testing. Thus generalized tetanus
can be complicated with GBS. Therefore, the physician should keep
21
in mind that GBS could be an important cause of muscle weakness
in patients with tetanus.
Acknowledgement
This paper was supported in part by the Foundation of
Wonkwang University in 2015.
Conflict of interest: None to report.
References
1. Yuki N, Hartung HP. Guillain–Barré syndrome. N Engl J Med 2012;366:2294–304.
2. Baxter R, Bakshi N, Fireman B, Lewis E, Ray P, Vellozzi C, et al. Lack of association
of Guillain–Barré syndrome with vaccinations. Clin Infect Dis 2013;57:197–204.
3. Fokke C, van den Berg B, Drenthen J, Walgaard C, van Doom PA, Jacobs BC.
Diagnosis of Guillain–Barré syndrome and validation of Brighton criteria. Brain
2014;137:33–43.
4. Amare A, Melkamu Y, Mekonnen D. Tetanus in adults: clinical presentation,
treatment and predictors of mortality in a tertiary hospital in Ethiopia. J Neurol
Sci 2012;317:62–5.
5. Fan E, Cheek F, Chlan L, Gosselink R, Hart N, Herridge MS, et al., ATS Committee on
ICU-acquired Weakness in Adults; American Thoracic Society. An official Ameri-
can Thoracic Society Clinical Practice guideline: the diagnosis of intensive care
unit-acquired weakness in adults. Am J Respir Crit Care Med 2014;190:1437–46.
Jae Hoon Leea,*
Yun Su Hwangb
Ji Hyun Choc
a
Department of Internal Medicine, Wonkwang University College of
Medicine, 460, Iksandaero, Iksan 54538, Korea
b
Department of Neurology, Wonkwang University College of Medicine,
Iksan, Korea
c
Department of Laboratory Medicine, Wonkwang University College of
Medicine, Iksan, Korea
Corresponding Editor: Eskild Petersen, Aarhus, Denmark.
*Corresponding author. Tel.: +82-63-859-2647;
fax: +82-63-855-2025.
E-mail address: john7026@wku.ac.kr (J.H. Lee).
Received 1 December 2015