CASE REPORT  
Niger J Paed 2012; 39 (3): 140 – 143  
Adegoke SA  
Ayoola OO  
Oseni SBA  
Acute disseminated encephalomyelitis  
in two Nigerian children with typhoid  
fever  
DOI:http://dx.doi.org/10.4314/njp.v39i3,11  
Accepted : 9th February 2012  
Abstract The involvement of  
cerebellar syndrome due to acute  
disseminated encephalomyelitis  
(ADEM). In this report, we dis-  
cussed the symptomatology and  
management of post-Salmonella  
disseminated encephalomyelitis in  
children.  
central nervous system in children  
with typhoid fever is common.  
However, encephalopathy with fo-  
cal neurological signs, coma and  
cerebellitis is rare. We report two  
children from the South-western  
part of Nigeria with blood culture  
proven typhoid fever who devel-  
oped encephalopathy and acute  
(
)
Adegoke SA  
Ayoola OO, Oseni SBA  
Department of Paediatrics and  
Child Health,  
Obafemi Awolowo University  
Teaching Hospital,  
Ile-Ife, Nigeria  
E-mail :adegoke2samade@yahoo.com  
Tel : +2348035037560  
Key words: Cerebellar syndrome,  
Children, Encephalomyelitis, Fever,  
Typhoid.  
Introduction  
various analys3is of neuro-psychiatric manifestations of  
typhoid fever.  
Typhoid fever still remains a major public health prob-  
lem, with global annual incidence of about 21 million  
cases. The greater burden however, occur in the devel-  
We therefore, report two children from South-western  
Nigeria with culture proven typhoid fever, encephalopa-  
thy, acute cerebellar syndrome and Magnetic Resonance  
Imaging or histopathologic evidence of ADEM.  
1
oping countries with annual incidence of 10.2 – 50.3 per  
1
00, 000 population since most of these population nei-  
ther have adequ2 ate portable water nor proper waste dis-  
posal methods.  
Case 1  
Children typically present with fever, anorexia, head-  
ache, abdominal pains, diarrhoea, constipation and  
myalgia. Central nervous system involvement in typhoid  
fever which constitutes an important atypical presenta-  
tion in childhood has a reported incidence ranging from  
LJ, a 7 year old girl was admitted into the Children  
Emergency Room of the Wesley Guild Hospital Unit of  
Obafemi Awolowo University Teaching Hospitals’  
rd  
Complex, Ilesa on the 3 October, 2011 with high grade  
continuous fever of 8 days, headache, constipation,  
vomiting and abdominal distension of 3 days. She was  
conscious on admission, but was moderately dehydrated,  
5
resistance. They usually manifest with neuro-  
psychiatric features such as confusion, encephalopathy,  
to 35 pe3rcent depending on the age group and drug  
0
febrile (temperature was 39.1 C), dyspneic and tachyp-  
3
meningism, convulsions and focal neurological deficits.  
neic (respiratory rate was 68 cycles/ minute), tachy-  
cardic (heart rate 136 beats / minute) and moderately  
pale. The blood pressure was however normal, 100/60  
mmHg. Her abdomen was grossly distended, she had  
generalised as well as rebound tenderness, guarding and  
absent bowel sound. On neurological examination, her  
higher mental functions and cranial nerves were normal.  
There were no signs of meningeal irritation or sensory  
deficit and the muscle power was normal.  
In children, post-infectious CNS disease is common, and  
in most cases, they follow viral illness such as chicken  
pox, mumps, cytomegalovirus, Ebstein-Barr virus, Her-  
4
pes simplex and measles infection. However, bacterial  
agents such as Salmonella, Streptococcus and Campylo-  
4
bacter have been implicated. Disseminated encephalo-  
myelitis is an inflammatory disease involving multiple  
sites within the central nervous system. It is character-  
ised by a predemyelinating infection; encephalopathy  
The plain abdominal X-rays (Supine) and abdominal  
ultrasonography revealed features of gut perforation,  
intestinal obstruction and abscess collection in the peri-  
toneum. Blood culture confirmed Salmonella typhi,  
which was sensitive to Ceftriaxone, Genticin, Ofloxacin  
and Tarivid. The urine and stool microscopy, culture and  
(
seizure, coma and other focal neurological signs) and  
cerebellitis, manifesting with cerebellar ataxia and  
4
tremor. This disease entity as a complication of enteric  
fever is very rare and only few cases had been reported  
5
in India. In Nigeria, none has been reported despite  
1
41  
sensitivity were normal. The haematological profile  
showed moderate anaemia (Packed Cell Volume of  
intravenous dexamethasone and later oral prednisolone.  
Eleven days after admission, she was no longer having  
cerebellar signs and also not aphasic or visually im-  
paired. She was subsequently discharged on oral Predni-  
solone 5 weeks after admission. She was yet to be seen  
at follow-up clinic at the time of writing this report.  
2
mm ); neutrophilia (69% neutrophils); normal serum  
electrolytes (sodium = 134 mmol/L; potassium =  
2%); leucopaenia (total white cell count of 2, 200 /  
3
3
.8mmol/L; Chloride 116 mmol/L; bicarbonate = 21  
mmol/L). Although, blood urea was elevated (9.8mmol/  
L), creatinine (95µmol/ L) and the liver enzymes were  
within normal limit. She was commenced on intrave-  
nous ceftriaxone and metronidazole. She also had sur-  
gery to drain the peritoneal abscess and repair of the  
ileal perforation within two hours of presentation. The  
immediate post-operative period was uneventful.  
Case 2  
AS, a 12 year old boy was admitted to the Children  
Emergency Room of the Ekiti State University Teaching  
Hospital, Ado-Ekiti, Ekiti State, Nigeria on 15 August,  
2011 with continuous fever of two weeks, vomiting,  
diarrhoea, and abdominal pain of four days. On exami-  
nation, he was conscious but irritable and acutely ill-  
th  
Fifty-two hours after the surgery, she had two episodes  
of generalised tonic-clonic convulsions and became un-  
conscious (Glasgow Coma Score of 7/15). She had posi-  
tive signs of meningeal irritation, global hypertonia and  
hyperreflexia with sustained ankle clonus. Diagnosis of  
typhoid septicaemia with encephalitis was made. The  
repeat serum electrolytes, urea, creatinine and random  
blood sugar were normal. The cerebrospinal fluid analy-  
0
looking. He had a temperature of 39.4 C, was dyspneic  
and tachypneic (respiratory rate 72 cycles per minute).  
He was also lethargic, moderately dehydrated and pale.  
He had a normal blood pressure of 95/60mmHg but was  
tachycardic with heart rate of 128 beats/ minute and in  
sinus rhythm. Heart sounds and intensity were normal  
with no murmur. The lung fields were also clear on aus-  
cultation. His abdomen was however tense with general-  
ized tenderness and guarding on palpation. There was no  
rebound tenderness and the bowel sounds were hyperac-  
tive. The spleen and liver were not palpably enlarged  
and there was no other mass noted. Neurological exami-  
nation was normal at presentation.  
3
sis showed pleocytosis (WBC > 12/mm ) and elevated  
protein (72g/ dl). It was however sterile (no organism  
was identified or cultured). She had Magnetic Reso-  
nance Imaging (MRI) because of repeated convulsions,  
deepening coma, focal neurological signs and absent  
pupillary reflex. This revealed widespread large globular  
lesions affecting the subcortical white matter. The  
periventricular structures were however normal. There  
was also no evidence of intraparenchymal or intraven-  
tricular collection (figure 1).  
Initial laboratory findings revealed the following: Mod-  
erate anaemia with Packed Cell Volume (PCV) of 25%;  
leucopaenia with total white cell count of 2,800/ mm ,  
3
3
and normal platelet count of 132, 000/ mm . Although  
he was acidotic with serum bicarbonate of 17 mmol/ L,  
other serum electrolytes and glucose were normal. So-  
dium was 135mmol/l, potassium was 3.2mmol/ L, chlo-  
ride was 108mmol/ L and random blood sugar was 4.8  
mmol/ L. In addition, the serum total protein and albu-  
min were normal: 77 g/l and 36 g/l respectively. How-  
ever, the liver enzymes were elevated (Alkaline Phos-  
phate, = 131U/L; Aspartate aminotransferase, = 300U/L;  
Alanine Aminotransferase, = 73U/L) and serum total  
bilirubin (245µmol/ l).  
Abdominal ultrasonography showed minimal fluid col-  
lection in the peritoneum and the plain (erect and su-  
pine) abdominal X-rays showed slightly enlarged large  
bowel loops but no air under the diaphragm. Diagnosis  
of enteric fever (typhoid septicaemia) was made based  
on her clinical presentation and laboratory findings. He  
was managed with intravenous Ceftriaxone and metroni-  
dazole. On the fourth day of admission, the blood cul-  
ture done at presentation confirmed Salmonella typhi  
which was sensitive to Ofloxacin, Ceftriaxone, Cipro-  
floxacin, Imipem and Amikacin but resistant to Gen-  
ticin, Cotrimoxazole and Cefuroxime. However, the  
urine and the stool were sterile. Ceftriaxone was there-  
fore continued due to steady progress in the clinical  
state.  
Fig 1: A saggital T1 weighted MRI scan of the brain  
The arrow shows an hyperintense lesions affecting the  
subcortical white matter. The periventricular structures  
were normal and there was no evidence of intraparen-  
chymal or intraventricular collection.  
She regained consciousness 22 hours later but subse-  
quently developed bilateral cerebellar signs such as  
tremor, ataxia, nystagmus and dysdiadocokinesia. Also,  
she had bowel and urinary incontinence, expressive and  
receptive aphasia as well as visual impairment.  
th  
Based on the post-infectious encephalopathy, cerebellitis  
and the MRI findings, diagnosis of acute disseminated  
encephalomyelitis was made. She was commenced on  
By the 9 day of admission, his condition deteriorated.  
Initially, he had fine tremor, tachycardia, tachypnoea  
0
and temperature of 40.3 C. Later, he had several epi-  
1
42  
sodes of generalised tonic-clonic convulsions, became  
deeply unconscious (Glasgow Coma Score of 4), his  
pupils became unreactive to light, had global hypertonia  
and hyperreflexia with sustained ankle clonus, hyperten-  
sion and bradycardia. Due to the suspected raised intrac-  
ranial pressure, he was giving hyperventillation and IV  
patients with cerebellitis or basal ganglia lesion. Al-  
though they (except tremors) were absent in the second  
child possibly because of the short duration of stay fol-  
lowing convulsion, he had histopathologic features of  
cerebellitis.  
1
0% mannitol, however, he died about 2 hours after the  
Typically, patients with ADEM present with encephalo-  
4
,7  
onset of convulsion. Lumbar puncture could not be done  
before his demise due to the severe cardiopulmonary  
instability and suspected intracranial hypertension. Also,  
CT scan or MRI was not done because of financial con-  
straint.  
pathy and cerebellar ataxia. It has been reported that  
the neurological presentation in ADEM vary from an  
acute explosive onset, with a maximum neurological  
deficit attained within 1 day, to more indolent progres-  
4
sion with maximum deficit of 31 days. In several re-  
ports, most children with ADEM (up to 90 percent) had  
polysymptomatic encephalopathy and cerebellar dys-  
His autopsy revealed congestion of the terminal  
4
,7  
1
0 – 15cm of the ileum. The mesenteric lymph nodes  
function. They may also present with facial weakness,  
dysarthria, dysphagia, ophthalmoplegia, visual impair-  
ment arising from optic neuritis; acute flaccid parapar4e,7-  
sis and urinary dysfunction resulting from myelitis.  
Our first patient had most of these features. Also, cere-  
brospinal fluid of this patient showed a mild pleocytosis,  
slight protein increase and sterile cultures, which agr4e-6es  
with most reports on post-typhoid encephalomyelitis.  
were enlarged, but there was no area of ulceration or  
haemorrhage. On histology, there was thinning of the  
mucosa of the terminal ileum, effacement of its villi and  
loss of mucosa glands. The submucosa was infiltrated  
by numerous lymphocytes. The mesenteric lymph nodes  
as well as the vessels of the submucosa were also con-  
gested, in keeping with typhoid ileitis. Grossly, there  
was slight oedema of the brain, but no area of haemor-  
rhage or necrosis. However, on histology, there was a  
widespread demyelination of the brain, especially  
around the microglial cells and the small vessels of the  
pons, midbrain and cerebellum. The impression was  
therefore acute disseminated encephalomyelitis in a  
child with typhoid septicaemia.  
There are few reports on the brain MRI findings in chil-  
dren with ADEM, particularly in the developing nations.  
These findings include areas of hyperintense lesions in  
the subcortical regions of the brain stem and the cerebel-  
4
9
lum. According to Ahmed et al, theyare thought to be  
due to cytotoxic and or diffuse vasogenic cerebral oe-  
dema. Other MRI findings in typhoid encephalopathy  
include bilateral symmetrical hypodensity with slight  
hypertrophy of the gyri6 and diffuse cerebral oedema  
without any focal lesion.  
Discussion  
In patients with ADEM, intravenous methylprednisone  
or dexamethasone, followed by oral Prednisolone have  
been reported to be effective, usually leading to im-  
Characteristically, acute disseminated encephalomyelitis  
which is a form of post infectious encephalopathy result  
from viral infecti5o,6ns. However, the present case reports  
4
,10  
proved recovery and less disability. The first patient  
who had steroid improved steadily with no obvious neu-  
rologic sequelae at discharge. Other treatment modalities  
include immunomodulatory therapies such as the use of  
immunoglobulins and plasmapharesis. The survival rates  
of patients with ADEM is usually high, especially if  
they are able to overcome the initial acute complications  
such a4s,10intracranial hypertension and metabolic derange-  
like few others  
show that it can also be caused by  
bacterial infections such as typhoid fever.  
Although, there are many postulations on the pathogene-  
sis of CNS involvement in typhoid fever; the exact  
4
,
pathogenesis is still unclear. Some of the factors impli-  
cated include hyperpyrexia, hypovitaminosis, metabolic  
derangements such as hypoglycae,8mia, hyponatremia,  
ment.  
Sadly, our second patient who deteriorated on  
7
hypernatremia and hypocalcemia. Others are toxae-  
the 9th day apparently because of these initial complica-  
tions, died before the diagnosis of ADEM was made  
histopathologically. In undiagnosed and or untreated  
patients, the mortality rate may be as high as 20 percent,  
and the 7risk of permanent neurological deficits 10 30  
percent.  
mia, cerebral oedema, secondary neuronal changes and  
non-specific inflammatory changes in the vessels of the  
brain. These non-specific inflammatory changes include  
capillary thrombosis, haemorrhage, oedema, and  
perivascular infilteration associated with widespread  
4
demyelination. Both patients had widespread demyeli-  
nation of the brain. This was confirmed in the first pa-  
tient by MRI scan of the brain and in the second by  
histopathology.  
Typhoid fever is associated with several neurological  
complications including post-infectious demyelination  
as the underlying pathological process. This is usually  
reversible but occasionally may be irreversibly lethal if  
left untreated. Since clinical diagnosis of ADEM may  
not be clear initially and in the absence of brain MRI  
scan, paediatricians, particularly those who work in re-  
source-poor countries, should consider this diagnosis in  
children with typhoid encephalopathy associated with  
Typhoid encephalitis has been regarded as a very un-  
3
usual complication and it is usually a late feature of  
typhoid fever, as shown by our patients.In addition, the  
first patient had tremor, choreoathethoid movement,  
ataxia and dysdiadocokinesia. These features are seen in  
1
43  
cerebellar dysfunction. Also, more work needs to be  
done in this area to determine the burden of this disease  
and factors predictive of its mortality.  
Authors’ contributions  
Adegoke SA: Conceived the study, did literature search  
on the subject, managed the patients and  
did the manuscript writing, editing and  
review.  
Ayoola OO: Involved in the management of the patients,  
manuscript editing and review.  
Acknowledgement  
Oseni SBA: Involved in the management of the patients  
and manuscript review.  
Conflict of interest: None  
We are grateful to all those who assisted us during the prepara-  
tion of this paper. We also acknowledge with thanks, all our  
colleagues who were involved in the management of these  
patients.  
Funding : None  
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