Cranial Nerves Palsy & Presenting Ocular Symptoms in Patients with Tuberculous Meningitis

Objective: To determine cranial nerve (CN) involvement in tuberculous meningitis (TBM) patients at the time of presentation.
Methodology: A cross sectional study was performed among 100 TBM patients with CN palsy as the presenting complaint.
TBM diagnosis was made on the clinical findings, cerebrospinal fluid (CSF) examination, and computed tomography (CT)
scan.
Results: Out of 100 TBM cases, 24 patients (24.0%) presented with CN palsy. Among 24 patients with CN palsy, abducens
nerve (CN VI), oculomotor nerve (CN III), trochlear nerve (CN IV), and facial nerve (CN VII) palsy was observed in 8
(33.3%), 7 (29.2%), 5 (20.8%), and 4 (16.7%) patients, respectively.
Conclusion: CN VI and CN III are the most commonly affected nerves in TBM followed by CN IV and CN VII. The results
showed that patients presenting with CN palsy should be evaluated for TBM in order to initiate proper treatment.
Key words: Tuberculous meningitis, Cranial nerve palsy

INTRODUCTION

Mycobacterium tuberculosis (MTB) has long been recognized as the causative agent of tuberculosis (TB). 1About one third of the world’s population is estimated to be infected with MTB, with Asia being the highest prevalence region of TB. 1Tuberculous meningitis (TBM) is the serious complication of TB with high mortality and morbidity rates. 2 The estimated risk of deaths from TBM is 15 - 32%. 3, 4 Delayed treatment and advanced stage disease are poor prognostic factors of TBM. Ho?o?lu et al. demonstrated that TBM patient admitted in the hospital with CN palsy are at risk of developing severe neurological deficits. 5Kalita et al. observed CN palsy in 23% cases of TBM. 6Another study conducted at Karachi (Pakistan) demonstrated 22.5% cases of TBM with CN palsy. 7 TBM patients may present with headache, altered mental status, signs of meningeal irritation, and/or CN deficits.
 


1,2. Assistant Professors,3 Senior Registrar, 4. House Officer 5 Professor
& HOD Division of Neurology, Department of Neurosciences,


Correspondence: Dr Muhammad Moosa, Division of Neurology,
Department of Neurosciences, Sharif Medical and Dental College,
Sharif Medical City Hospital, Jati Umra Road off Raiwind Road,
Lahore, Pakistan. E-mail: moosaljr@gmail.com Cell: 03006702740
necs.kpr@gmail.com 0322 4736428, dramna.malik@hotmail.com


CN VI and III are the most commonly affected nerves in TBM followed by CN IV and VII. The results showed that patients presenting with CN palsy should be evaluated for TBM in order to initiate proper and early treatment.


Out of 12 pairs, cranial nerves emerging from the midbrain are more likely to be affected by TBM, followed by cranial nerves originating from the pons. It has been demonstrated that CN VI is affected most frequently by TBM, followed by CN-III, -IV, and -VII. 8The present study aimed to determine the frequency of CN palsy in patients with TBM at the time of presentation. The diagnosis of TBM was based on clinical manifestations, CSF examination, and CT scan brain (contrast) of the patients.

METHODOLOGY

A total of 100 patients including 64 male and 36 female, aged 18-60 years (mean age 37.6 ± 5.7 years) were included in the study. The study was conducted at Sharif Medical City Hospital (Lahore, Pakistan) over a period of three years between September, 2015and September, 2018. Written informed consent was obtained from all patients. TBM patients with any of the following features were included in the study: CT brain (contrast) suggestive of TBM, Typical CSF findings of TBM, Acid fast bacilli culture or smear positive in CSF examination, family history of TBM and/or history of contact with tuberculous patients, positive Mantoux Test of more than 10 mm. Meanwhile, patients with one of the following were excluded from the study: Brainstem encephalitis confirmed on CSF examination and/or neuroimaging, pyogenic meningitis confirmed on CSF examination, CT scan suggestive of brainstem infarction and hemorrhage, History of acute head trauma (less than 3 months). Data were analyzed using SPSS version 21.0. The quantitative variables like age were presented by calculating the mean and standard deviation. The frequency and percentage were calculated for gender and CN palsy.

RESULTS

A total of 100 patients were included in this study.Out of 100 cases, 18 patients (18.0 %) were < 20 years old, 67 patients (67.0 %) were 20-40 years old, and 15 patients (15.0 %) were 41-60 years old. The mean age of patients was 37.6 ± 5.7 years (Table 1).



Regarding gender distribution, 64 patients (64.0%) were male, while the remaining 36 patients (36.0%) were female (Table 2).



CN palsy was observed in 24 patients (24.0%), (Table 3).



Among 24 cases with CN palsy, 8 patients (33.3%) presented with CN VI palsy, 7 patients (29.2%) presented with CN III palsy, 5 patients (20.8%)presented with CN IV palsy, and 4 patients (16.7%) presented with CN VII palsy. 

DISCUSSION

TBM, with significant mortality and morbidity, is a feared complication of TB infection. The common clinical manifestations of TBM include headache, fever, and the presence of signs of meningeal irritation. Other manifestations may include diminished cognition, seizures, paresis, and CN palsy9. Chotmongkol and colleagues10 found clinical presentation of headache, fever, stiff-neck, mental impairment, motor weakness, and CN palsy in 95.6%, 91.1%, 77.8%, 40.0%, 11.1%, and 11.1% cases of TBM, respectively. In the present study, CN palsy was observed in 24 patients (24.0%) with TBM. Our findings are consistent with the study of Fazel et al.7 where they reported CN palsy in 22.5% of patients with TBM. It has been observed that CN VI is usually involved first and is most frequently affected11-13 in TBM. The lateral rectus muscle is innervated by CN VI and patients with CN VI palsy present with difficulty in moving the eye laterally. In the current study, the most frequently involved CN was also CN VI. Out of 24 cases with CN palsy as the presenting complaint, CN VI palsy was observed in 8 patients (6 patients with unilateral and 2 patients with bilateral lateral rectus palsy). The extra-ocular muscles other than the lateral rectus and superior oblique muscles are supplied by CN III. In patients with CN III palsy, the eye is displaced downward and outward. In the present study, the second most frequently involved CN was CN III. Out of 24 cases with CN palsy as the presenting complaint, CN III palsy was observed in 7 patients. The superior oblique muscle is innervated by CN IV and is responsible for intorsion and depression of the eye. Patients with CN IV palsy present with diplopia (vertical) which is exacerbated on inward and downward movement of the eye. In our study, out of 24 cases, CN IV palsy was observed in 5 patients. CN VII is a mixed (sensory and motor) cranial nerve. The motor component of CN VII is involved in controlling facial expression muscles, while the sensory component of CN VII is responsible for the anterior two-third taste sensation of the tongue. Patients with CN VII palsy present with flattening of the nasolabial fold and difficulty in closing the eye. In the present study, out of 24 cases with CN palsy as the presenting complaint, CN VII palsy was observed in 4 patients. TBM often presents non-specifically and is diagnosed when brain is already affected. Therefore, the outcome of TBM can be improved with early diagnosis. Komolafe et al. 14 advocated the formation of exudates at the base of the brain in TBM causing cerebral vasculitis and central nervous system pathologies, thereby blocking cerebrospinal fluid (CSF) route and entrapping cranial nerves. TBM diagnosis may only be based on CSF and clinical findings in the absence of confirmation of definitive microorganism. Decreased glucose and increased protein levels with predominant lymphocytes are classical findings of CSF in TBM. A single CSF sample for acid fast bacilli has low sensitivity (20 – 40%). 15 It has been demonstrated that multiple CSF samples can increase the sensitivity to 85%. 16 The use of ELISA assays to detect antibodies in the CSF against specific microorganism antigens is limited due to affordability issue, especially in developing countries. 17, 18 Neuroimaging may aid to diagnose TBM. Hydrocephalus and basal meningeal enhancement are classical neuroimaging features of TBM. 15, 19, 20 Basal meningeal enhancement with 100% specificity and 89% sensitivity have been proposed in patients with TBM.21 In the present study, we used CSF and neuroimaging (CT Brain with contrast) findings in addition to clinical manifestations of patients to diagnose TBM. The poor prognosis of TBM is related to the advanced stage of the disease, hydrocephalus, and positive CSF findings.22

CONCLUSION

CN VI and CN III are the most commonly affected cranial nerves in TBM followed by CN IV and CN VII. Patients presenting with CN palsy should be evaluated for TBM in order to initiate proper treatment.

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