ORIGINAL ARTICLE

JIACM 2003; 4(3): 196-9

Neurological Manifestations of Enteric Fever

Manoj Lakhotia*, RS Gehlot**, Pravesh Jain***, Sanjeev Sharma****, Amita Bhargava*****

Abstract
Introduction : Enteric fever represents a spectrum of acute systemic febrile illness with a myriad of presentations and complications.
Neurological manifestations constitute an important, but often under-diagnosed constituent of this spectrum.
Aims : This study was carried out to evaluate the incidence, clinical pattern, and outcome of neurological manifestations in enteric
fever patients of Western Rajasthan.
Material and methods : A total of 232 patients of enteric fever, admitted between 1999 and 2001, at Mahatma Gandhi hospital,
Jodhpur were evaluated. The diagnosis of enteric fever was based on typical presentations, blood culture, serial Widal test titres,
and culture of urine, stool, and gastrointestinal secretions. CT scan of brain, CSF study, and electrophysiological studies of the
nervous system were done in appropriate patients.
Results : In this study, the average age of patients was 36.9 8.3 years, with males comprising 71.4% (n = 165) and females
28.6% (n = 67). Mean duration of fever was 14.8 5.6 days (range 7 to 30 days). Neurological manifestations were seen in
63 (27.1%) patients. Of these, 27 (42.8%) patients had typhoid delirium state and 36 (57.2%) had specific neurological
complications. Amongst specific neurological complications, encephalitis (25%), psychiatric manifestations (19.44%),
cerebellar ataxia (19.44%), and meningitis (13.89%) were the dominant features. Mortality rate amongst patients with
neurological manifestations was 6.35% (n = 4).
Conclusions : The results of this series corroborated favourably with the incidence of neurological manifestations of enteric fever
reported elsewhere in this country and abroad, and reinstates the importance of their early detection during the course of enteric
fever.
Key words : Typhoid delirium, Encephalitis, Cerebellar ataxia, Psychiatric disorders.

Introduction
Enteric fever represents a spectrum of acute systemic
febrile illness of prolonged duration, characterised by
hectic rise of fever, bacteraemia, delirium, and a wide
accompaniment of systemic manifestations. It is caused
due to widespread dissemination of infection by
predominantly Salmonella typhi, and to a lesser extent,
Salmonella paratyphi A, B and C1.
Although, traditionally the hallmark of enteric fever
was considered as fever and abdominal pain, with
evolution of this disease through the ages, its critical
presentations have exhibited a high level of
polymorphism in 50% cases in some series2. The typical
clinical features may not be seen in all patients and
the disease may instead manifest in an atypical form
of which neurological manifestations constitute an
important but often under diagnosed component of
the entire spectrum.

This observational study was carried out to evaluate the

incidence, clinical pattern, and outcome of neurological
manifestations in enteric fever patients of Western
Rajasthan.

Subjects and methods

This study was conducted at Mahatma Gandhi hospital,
affiliated to Dr. S. N. Medical College and associated
hospitals, Jodhpur, Rajasthan. This hospital, being
reference health centre, caters to the medical needs of
a substantial fraction of the population of Western
Rajasthan.
A total of 232 patients of enteric fever, who were admitted
in a period of approximately three years between 1999
and 2001, were enrolled in this study. Patients with a
relevant past history of neurological and psychiatric
diseases were excluded from this study. Similarly, patients
with a previous record of chronic liver diseases, connective

* Associate Professor, ** Professor, *** Post Graduate Resident, **** Ex-Senior Resident, ***** Assistant Professor
(Neurology), Department of Medicine, Dr. S. N. Medical College, Jodhpur, Rajasthan.

tissue disorders, renal failure, diabetes mellitus, and

chronic alcohol addiction were not incorporated in our
study.

1. Typhoid delirium state or typhoid toxaemia : 42.8%

(n = 27).
2. Specific neurological complications : 57.2% (n = 36).

All selected patients underwent a detailed historical and

clinical evaluation pertaining to all relevant systems. All
patients were subjected to an extensive battery of
investigations including a complete haemogram, liver
function tests (serum transaminases, bilirubin, total
protein and its fractions, and prothrombin time), renal
function tests (blood urea, serum creatinine, and serum
electrolytes), urine examination, chest X-ray, and
ultrasonography of abdomen.

Typhoid delirium state was the ear liest

neurological symptom observed in this study,
which occured 2 to 18 days (mean 5.9 days) after
the onset of fever. The mean duration of this
condition was 7.3 days (range: 3-14 days), and
following the initiation of appropriate
therapeutic measures, the mean time of
resolution was 3.3 days (range: 1-7 days). It was
charac terised by restlessness, c onfusion,
incoherent sp eech, disorientation, and
carphology (flocillations) (Fig. 1).

A definitive diagnosis of enteric fever was established in

all cases based on blood culture (especially buffy coat),
culture of urine, stool, gastric, and intestinal secretions, and
serial estimation of Widal test titres depending on the
temporal presentation of patients. Special tests pertaining
to the nervous system that were performed included CSF
study (including culture), CT scan of brain, MRI of brain,
and electro-physiological studies (nerve conduction
studies) when indicated in appropriate cases. In patients
with neuropsychiatric symptoms, evaluation by a panel
of experienced psychiatrists was done.

Specific neurological complications were present

in 57.2% (n = 36) of patients. The common
manifestations included encephalitic disorders in
25% (n = 9) as the commonest, closely followed by
psychiatric disorders, and cerebellar ataxia in
19.44% (n = 7) of patients each. Other prominent
manifestations included meningitis (13.89%; n =
5); polyneuropathy (8.33%; n = 3); and extrapyramidal syndromes (5.56%; n = 2) ( Table II and
Fig. 2). Also, one case each of transverse myelitis,
facial nerve palsy, and optic neuritis was seen.

Appropriate therapeutic interventions were undertaken

concomitantly in all patients, including parenteral
ceftriaxone sodium, intravenous fluids, antipyretics, and
antipsychotics (haloperidol, chlorpromazine) whenever
indicated .

Of all 63 cases with neurological manifestations,

mortality was seen in 4 cases (6.35%) all deaths were
attributed to encephalitic illness.

Observations
Among the 232 patients enrolled in this study,
the majority (71.12%) were males (n = 165),
while females were 28.88% (n = 67). The
average age of patients was 36.9 8.3 years.
The mean duration of fever in all patients was
14.8 5.6 days with a range of 7 to 30 days.
Common presenting symptoms and signs are
depicted in table I.
Neurological manifestations were diagnosed in
27.1% (n = 68) of the above 232 patients.
Patients with neurological manifestations were
Fig. 1. Clinical features of patients with typhoid delirium state.
broadly categorised into two groups:

Journal, Indian Academy of Clinical Medicine

Vol. 4, No. 3

July-September 2003

197

Table I : Common symptoms and signs in study patients.

Common symptoms
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.

Fever
Anorexia
Headache
Abdominal pain
Nausea/vomiting
Diarrhoea
Constipation
Myalgia/arthralgia
Pharyngitis/cough
Malena

(%)
:
:
:
:
:
:
:
:
:
:

Common signs

100%
83%
80%
52%
51%
43%
40%
31%
26%
12%

1.
2.
3.
4.
5.
6.
7.

(%)

Coated tongue
Hepatomegaly
Splenomegaly
Toxic symptoms
Relative bradycardia
Rhonchi
Rose spots

:
:
:
:
:
:
:

83%
50%
32%
30%
12%
4%
3%

Table II : Individual characteristics of specific neurological complications.

Specific neurological
complications

Common
manifestations
(%)

I.

Encephalitic disorders
(n = 9)

Coma
Semicoma
Meningism
Seizures

:
:
:
:

II.

Psychiatric disorders
(n = 7)

Paranoid psychosis
Hysteria
Delirium
Aggressive behavior
Gait ataxia
B/L finger nose ataxia
Dysdiadocokinesia
Hypotonia

III. Cerebellar ataxia

(n = 7)

Mean onset
in days
(range)

Mean
duration
in days
(range)

Mean time
for resolution
in days
(range)

55%
40%
46%
26%

9.9
(5-14)

11.4
(8-18)

19.3
(11-30)

:
:
:
:

56%
50%
50%
34%

11.2
(7-18)

24.1
(11-34)

:
:
:
:

78%
56%
45%
33%

14.8
(7-28)

> 25
days*

* Exact figures could not be estimated due to lack of further follow-up.

Discussion

Fig. 2 : Break-up of patients with specific neurological complications of enteric fever.

198

In the past 20 years, reports from India, Papua New

Guinea, Nigeria, and Indonesia have documented
a wide spectrum of neurological complications in
cases of typhoid fever3. The exact pathogenesis of
these complications is not known. Metabolic
disturbances, toxaemia, hyperpyrexia, and nonspecific cerebral changes such as oedema and
haemorrhage have been hypothesised as possible
mechanisms4. The pathological process in the
brain causing enteric fever encephalopathy may

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Vol. 4, No. 3

July-September 2003

Gastrointestinal disease. 5th Ed. Philadelphia,W.B. Saunders,

1993; 1128-73.

be related to acute disseminated encephalomyelitis5.

The incidence of 27.1% pertaining to neurological
complications as reported in this study, favourably
matches with those reported elsewhere 3,6. Typhoid
delirium state also commonly referred to as typhoid
toxaemia is one of the earliest and perhaps the
commonest neurological complication in enteric fever, but
is often underdiagnosed due to its lack of specificity. It is
considered to be an acute brain syndrome, which is usually
seen concomitantly with the height of pyrexia, and clears
quickly following the initiation of treatment7. Osuatukon
et al6 found an incidence of 57% in their study, while
elsewhere in India, Sharma and Gathwala have reported
in 42.4% cases8. In our subjects we found the incidence of
typhoid toxaemia to be 42.8%.
Amongst the specific neurological complications,
encephalitic illness in our series constituted 25% of the
cases with neurological complications. In a series of 959
Nigerian subjects by Osuatukon et al 6, the overall
incidence of similar encephalitic illness was 10.53%. In
both these studies, Salmonella species could not be
isolated from CSF examination.

2.

Bulter T, Islam A, Kabeer I et al. Patients of morbidity and

mortality in typhoid fever dependant on age and gender :
Review of 552 hospitalised patients with diarrhea. Rev Inf
Dis 1991; 13: 85-90.

3.

Khosla SW, Srivastava SC, Gupta S. Neuropsychiatric

manifestations of typhoid. J Trop Med Hyg 1977; 80: 93-5.

4.

Cohea JL et al. Extraintestinal manifestations of salmonella

infections. Medicine 1987; 66: 349-53.

5.

Wadia RS, Dhadphale S, Kulkarni R et al. Neurology of enteric

fever. Revs. Neurol 1994; 1: 57-65.

6.

Osuntukon BO, Bademossi O, Ogunremi K et al .

Neuropsychiatric manifestations of typhoid fever in 959
patients. Arch Neurol 1972; 27: 7-13.

7.

Hauqe A. Neurological manifestations of Enteric fever. In :

Chopra JS, Sawhney IMS, eds. : Neurology in Tropics. 1st Ed.
New Delhi, B.I. Churchill Living Stone,. India. 1993; 506-11.

8.

Sharma A, Gathwala G. Clinical profile and outcome in

enteric fever. Indian Pediat 1993; 30 (1): 47-50.

9.

Wadia RS, Ichaporia NR, Kimalkar RS et al. Cerebellar ataxia

in enteric fever. J Neurol Neurosurg Psychiat 1985; 48: 695-7.

Psychiatric illness may complicate enteric fever either as

a presenting complaint or may also develop during the
evolution of disease. Wadia et al 9 reported a near
equivalent incidence of 15% in their study, while incidental
reports by Osuatukon et al have quoted a figure of 0.7%.
Cerebellar ataxia may develop in isolation or may also
occur concomitantly with other features. In 1985 Wadia
et al9 described 28 cases of enteric fever with cerebellar
ataxia with 25% occurrence in first week and 61% in
second week. Our study had an incidence of 19.44% with
a mean onset of 14.8 days (7-29 days).
Hence, concluding this study, it would be important to
validate that, neurological manifestations constitute an
important and integral component of atypical enteric
fever presentation. It remains a challenge to the physician
to diagnose such patients at an early stage and
accordingly manage them.

References
1.

Gorbach Sl. Infectious diarrhea and bacterial food

poisoning. In: Sleisenger MH, Fordtran JS, eds.

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