Material and methods : A total of 232 patients of enteric fever, admitted between 1999 and 2001, at Mahatma Gandhi hospital,. Jodhpur were evaluated.
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:
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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.
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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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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.
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Cohea JL et al. Extraintestinal manifestations of salmonella infections. Medicine 1987; 66: 349-53.
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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.
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Sharma A, Gathwala G. Clinical profile and outcome in enteric fever. Indian Pediat 1993; 30 (1): 47-50.
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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.
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