The objective of this study was to identify asymptomatic patients with brain MRI lesions suggestive of multiple sclerosis (MS) in a low-prevalence area of Pakistan. Brain MRIs for 864 patients were reviewed at the Aga Khan University (Karachi, Pakistan) during an 8-month period of 2006 and 2007 to identify patients with lesions suggestive of MS. The lesions were characterised based on modified Barkhof criteria. Six (two females) (0.7%) of 864 patients fulfilled brain MRI criteria suggestive of MS. The mean number of MRI lesions (total lesions on T2) were 9 (range 5–14). Although Pakistan is considered a low-prevalence area for MS, 0.7% of brain MRI scans in patients without clinical MS symptoms showed lesions fulfilling brain MRI criteria of MS.
- multiple sclerosis
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Incidental MRI findings suggestive of multiple sclerosis (MS) in asymptomatic patients (radiological isolated syndrome) have recently been reported.1 2 In one study they reported a long-term follow-up of 44 patients and radiological progression was identified in 59% of the scans and 25% developed definite MS or clinically isolated syndrome.1 Another study showed that 11 of 30 patients (35%) with incidental MRI findings developed MS.3
A low prevalence of MS has been reported in East and Southeast Asia.4 MS is uncommon in Pakistan.5 There are no reported population-based incidence or prevalence studies for MS from Pakistan. There are no published data reporting incidental MS in Pakistan. The objective of this study was to identify asymptomatic patients with brain MRI lesions suggestive of MS in a low-prevalence area of Pakistan.
During the study period, 2302 MRI studies were performed in all age groups. For the age group of 15–40 years, 877 MRI scans were performed. Of these, 12 patients had known history of MS (based on MRI requisition form) and one patient had clinical symptoms consistent with MS (based on chart review of patient). Thus, 864 MRI scans were included in the study. The reasons for MRI were collected from MRI requisition forms. The reasons for performing these MRI included headache 629, head trauma 57, psychiatric symptoms 45, dizziness 40, memory loss 39, seizure 7, transient ischaemic attack 6 and unspecified reason in 41 patients. We labelled reasons as unspecified if patients complain or symptom was not provided in requisition forms including rule-out tumour, rule-out hydrocephalus, and so on.
All patients underwent routine brain MRI protocol that included T1, T2 and fluid attenuation inversion recovery (FLAIR) sequences in axial, coronal and sagittal planes (Siemens 1.5-T Magnetom Avento; Siemens, Germany). Routine brain MRI protocol at Aga Khan University (AKU) uses slice thickness of 5 mm with interslice gap of 1.5 mm.
Brain MRIs for 864 patients were retrospectively (n=333) and prospectively (n=531) reviewed at the Aga Khan University (Karachi, Pakistan) during an 8-month period of 2006 and 2007 to identify patients with incidental lesions suggestive of MS. Of these 864 studies, 139 (16%) were postcontrast. The lesions were characterised based on the modified Barkhof criteria.6 Minimal diameter of the lesion or orientation of the lesion was not defined for inclusion in study. Juxtacortical lesion was defined as “touching the cortex” and periventricular lesion was defined as “touching the ventricle”.
Patients were excluded if they had a known history of MS or clinical symptoms consistent with MS and if aged <15 years and >40 years. All MRIs were reviewed by two radiologists and one neurologist. All patients fulfilling the modified Barkhof criteria were seen by a neurologist for detailed clinical history and neurological examination. The radiologists and neurologist reviewing the scans were not blinded. Patients were only included if MRI lesions were not better accounted for by another disease process. The study was approved by ethics review committee of the Aga Khan Hospital.
A summary of findings on all MRIs is given in table 1. Six (two females) (0.7%) of 864 patients fulfilled brain MRI criteria suggestive of MS. The reasons for MRI scans in these patients were headache (four patients), recent head injury and headache (one patient) and subjective memory loss and headache (one patient). These six patients were seen by a trained neurologist for neurological history and examination. Headaches were characterised as migraine (three patients), post-traumatic headache (one patient), tension-type headache (one patient) and mixed migraine and tension-type headache (one patient). All patients were found to have normal neurological examination. Age range was 17–40 years (mean 33 years). None of the patients had any risk factors for stroke (hypertension, diabetes, cigarette smoking or history of drug abuse) and none had a relative with MS. Serum B12, antinuclear antibodies and erythrocyte sedimentation rate were normal when tested (see table 2). None of the patients underwent cerebrospinal fluid analysis or visual-evoked potentials (VEP).
The mean number of MRI lesions (total lesions on T2) was 9 (range 5–14). Cervical spinal cord MRI done in one patient was normal (see table 2 for description of numbers and location). None of the patients underwent MRI with contrast enhancement.
These findings have important clinical implications. Although Pakistan is considered a low-prevalence area for MS, approximately 1% of brain MRI scans in patients without clinical MS symptoms showed lesions fulfilling brain MRI criteria of MS. The findings indicate that MS may be a more common disease in Pakistan than previously expected.
Clinical and radiological follow-up of these patients will be extremely important to study and evaluate the natural course. We plan to follow these patients clinically and repeat MRI after 1 year if there is no clinical progression.
The reason why scans from patients aged <15 years were excluded was logistical because the paediatric radiologist could not participate in the study. The reason for excluding patients aged >40 years was the higher prevalence of subcortical and small-vessel ischaemic lesions on MRI in the population >40 years and because onset of clinical MS is usually before this age.
We understand the limitations of modified Barkhof criteria as it is only validated as supporting the diagnosis of MS in patients with at least one attack consistent with MS. Currently, there are no validated criteria for use related to asymptomatic MS or radiologically isolated syndrome. The study by Okuda1 has somewhat validated this criteria for asymptomatic patients. A major limitation of the study is the lack of contrast-enhanced scans and limited laboratory workup. All patients were offered VEP, serum B12 levels, serum antinuclear antibody and erythrocyte sedimentation rate, but only few patients underwent complete workup mostly because of financial reasons (patients had to pay out of their pockets for these tests).
The exact population-based prevalence of MS is not known in Pakistan. An epidemiological study related to MS in Pakistan is currently underway. White matter abnormalities or unknown bright objects were present in 19 (2.5%) of MRIs. Six of these were included in the study. The rate of potentially non-specific white matter abnormalities in Pakistan would be approximately 13/864 or 1.5% for individuals aged 15–40. Awareness regarding significance of these lesions (radiological isolated syndrome) is important among neurologists and neuroradiologists. Future guidelines should address these patients for optimal treatment and follow-ups.
In conclusion, this is to our knowledge the first report on radiological isolated syndrome in a low-prevalence area indicating that incidental MRI lesions suggestive of MS may be more common than previously expected in Pakistan. Young age, absence of any cerebrovascular risk factors, number of lesions and no clear-cut explanation for these lesions lead us to think MS in these patients. We are still short of calling these patients as cases with MS based on established criteria. None of these patients was labelled or diagnosed as having MS. Clinical and radiological follow-up of these patients will be helpful in characterising these lesions.
These findings are accepted in preliminary form for platform presentation at the 61st Annual Meeting of the American Academy of Neurology (April 2009) at Seattle, USA.
Funding The study was supported by Department of Medicine, Aga Khan University.
Competing interests None.
Ethics approval This study was conducted with the approval of the Aga Khan University.
Provenance and peer review Not commissioned; externally peer reviewed.