Tuberculous optochiasmatic arachnoiditis and optochiasmatic tuberculoma in Malaysia

@#Background & Objectives: Arachnoiditis which involves the optic chiasm and optic nervecan rarely occurs in the patients with tuberculous meningitis (TBM). The primary objective of this study was to determine the incidence, assess the clinical and neuroimaging findings, and associations, understand its pathogenesis of these patients, and determine its prognosis. Methods: The patients admitted with TBM in the neurology wards of two tertiary care hospitals from 2009 to 2017 in Kuala Lumpur, Malaysia were screened. The patients with OCA and optochiasmatic tuberculoma were included in this study. We assessed the clinical, cerebrospinal fluid (CSF), imaging findings of the study subjects and compared with other patients without OCA or optochiasmatic tuberculoma. Results: Eighty-eight patients with TBM were seen during the study period. Seven (8.0%) had OCA and one (1.1%) had optochiasmatic tuberculoma. Five out of seven (71.4%) patients with OCA were newly diagnosed cases of TBM. The other two (28.6%) had involvement while on treatment with antituberculous treatment (paradoxical manifestation). The mean age of the patients with OCA was 27.3 ± 11.7. All the OCA patients had leptomeningeal enhancement at other sites. All had hydrocephalus and cerebral infarcts on brain neuroimaging. Three (42.9%) patients had cerebral tuberculoma at sites other than suprasellar and optic chiasm areas. On univariate analysis, the presence of OCA and optochiasmatic tuberculoma was associated with raised CSF opening pressure (p=0.014), younger age (p=0.024), cerebral infarcts (p=0.018) and hydrocephalus (p= 0.046). There was no statistically significant association on logistic regression. Only one (14.3%) patient had visual impairment. Conclusion: OCA and optochiasmatic tuberculoma were seen in 9% of a cohort of Malaysian TBM patients. They were more likely to be younger, have raised CSF opening pressure, cerebral infarcts and hydrocephalus, suggesting the association with a more severe exudative disease.

Spinal tuberculous disease is common in tuberculous meningitis

Background: Tuberculous disease of spine (spinal TB) is under-recognized in tuberculous (TB) meningitis.The objective of the study was to evaluate the frequency, clinical and neuroimaging changes, andoutcome in the patients with spinal TB. Methods: All the patients with spinal TB admitted in the twolargest tertiary hospitals in Kuala Lumpur from 2009 to 2017 were recruited, the clinical features weredocumented, the magnetic resonance imaging (MRI) of the spine was performed. Clinical outcome wasassessed with Modified Rankin scale (MRS). Results: Twenty two patients were recruited. This wasout of 70 TB meningitis patients (31.4%) seen over the same period. Eighteen (81.8%) patients hadconcomitant TB meningitis. The clinical features consisted of systemic symptoms with fever (63.6%),meningitis symptoms with altered sensorium (45.5%), myelopathy with paraparesis (36.4%). Thefindings on spinal MRI were discitis (36.4%), spinal meningeal enhancement (31.8%), spinal cordcompression (31.8%), psoas abscess (27.3%), osteomyelitis (22.7%), and cord oedema (22.7%). Allexcept two patients (90.9%) had involvement in psoas muscle, bone or leptomeningeal enhancement,features that can be used to differentiate from myelopathy that affect the parenchyma only, such asdemyelination. Unusual manifestations were syringomyelia and paradoxical manifestations seen in 3patients each. The outcome were overall poor, with 68% having MRS 3 or more.Conclusion: Spinal TB is common in TB meningitis. The outcome is overall poor. A heightenedawareness is crucial to enable early diagnosis and treatment.

Role of cytokines in the assessment of clinical outcome and neuroimaging findings in patients with tuberculous meningitis

Background: Tuberculous meningitis is a life-threatening manifestation resulting from infection by Mycobacterium tuberculosis, especially in the developing countries. The molecular aspects of pathogenesis of tuberculous meningitis remain poorly understood. We evaluated the correlation of cerebrospinal fluid (CSF) and serum cytokine levels with the clinical outcome of 15 HIV-negative patients with tuberculous meningitis. We also assessed the association of CSF and serum cytokines with neuroimaging of brain findings in the patients. Methods: The prospective longitudinal study was conducted at the University Malaya Medical Centre between 2012 and 2014. Neuroimaging of the brain was performed and the findings of leptomeningeal enhancement, hydrocephalus, tuberculoma, infarcts and vasculopathy were recorded. The CSF and serum specimens were analyzed for IL-1ß, IL-8, IL-10, IL-18, IP-10, IFN-γ, MCP-1, TGF-ß, VEGF, TNF- α, IL-18BPa and MMP-9. The clinical outcome was graded at 3 months based on Modified Rankin scale (mRS). Results: On admission and at one month of anti-tuberculosis treatment, the CSF levels of IL-8, IL-1β, IP-10, IFN-γ and VEGF were elevated in all of the patients. Serum IP-10, MCP-1, IL-1β and IL-8 levels were increased on admission and at one month of anti-tuberculosis treatment. There were statistically significant differences between good and poor outcome (mRS at 3 months) for CSF IFN-γ (p=0.033), CSF IL-10 (p=0.033) and serum VEGF (p=0.033) at one month of treatment. None of the patients showed any association between CSF and serum cytokines on admission and at one month of anti-tuberculosis treatment with neuro-radiological findings. Conclusion: The CSF cytokine levels were not related to TBM disease severity on admission, and changes on MRI/CT scans. CSF levels of IFN-γ and IL-10 at one month of anti-tuberculosis treatment were associated with clinical outcome at 3 months. CSF cytokine levels on admission were not associated with the clinical outcome.

Neuroimaging findings are sensitive and specific in diagnosis of tuberculous meningitis

Objective: The primary objective of this study was to describe the neuroimaging changes of tuberculous meningitis (TBM), and to determine the role of neuroimaging in the diagnosis of TBM. Methods: Between January 2009 and July 2015, we prospectively recruited TBM patients in two hospitals in Malaysia. Neuroimaging was performed and findings were recorded. The control consists of other types of meningo-encephalitis seen over the same period. Results: Fifty four TBM patients were recruited. Leptomeningeal enhancement was seen in 39 (72.2%) patients, commonly at prepontine cistern and interpeduncular fossa. Hydrocephalus was observed in 38 (70.4%) patients, 25 (46.3%) patients had moderate and severe hydrocephalus. Thirty four patients (63.0%) had cerebral infarction. Tuberculoma were seen in 29 (53.7%) patients; 27 (50.0%) patients had classical tuberculoma, 2 (3.7%) patients had “other” type of tuberculoma, 18 (33.3%) patients had ≥5 tuberculoma, and 11 (20.4%) patients had < 5 tuberculoma. Fifteen (37.2%) patients had vasculitis, 6 (11.1%) patients had vasospasm. Close to nine tenth (88.9%) of the patients had ≥1 classical neuroimaging features, 77.8% had ≥ 2 classical imaging features of TBM (basal enhancement, hydrocephalus, basal ganglia / thalamic infarct, classical tuberculoma, and vasculitis/vasospasm). Only 4% with other types of meningitis/encephalitis had ≥1 feature, and 1% had two or more classical TBM neuroimaging features. The sensitivity of the imaging features of the imaging features for diagnosis of TBM was 88.9% and the specificity was 95.6%. Conclusion: The classic imaging features of basal enhancement, hydrocephalus, basal ganglia/thalamic infarct, classic tuberculoma, and vasculitis are sensitive and specific to diagnosis of TBM.

PARK16 is associated with PD in the Malaysian population.

PARK16 was identified as a risk factor for Parkinson's disease in a Japanese cohort; however, subsequent studies in the other populations including the Chinese, European, Caucasian, and Chilean have shown a protective role instead. To investigate this locus in our Malaysian cohort, 1,144 individuals were screened for five SNPs in the PARK16 locus and logistic regression analysis showed that the A allele of the rs947211 SNP reduced the risk of developing PD via a recessive model (Odds ratio 0.57, P-value 0.0003). Pooled analysis with other Asian studies showed that A allele of the rs947211 SNP decreased the risk of developing PD via a recessive model (Odds ratio 0.71, P-value 0.0001). In addition, when meta-analysis was performed with other Asian population, three SNPs (rs823128, rs823156, and rs11240572) reduced risk of developing PD via a dominant model. © 2016 Wiley Periodicals, Inc.

The Importance of Early Recognition of Cerebral Venous Sinus Thrombosis: A Case Report.

A 33-year-old lady presented to the emergency department (ED) of Kuala Lumpur Hospital with subacute onset of headaches, irritability, and vomiting. Neurological examination revealed a restless agitated patient, poor responses to verbal commands with a Glasgow Coma Scale of 14/15, photophobia, blurred nasal margins with generalised weakness, hyperreflexia, and downgoing plantars. Computed tomography (CT) of the brain showed evidence of biparietal infarction with an empty delta sign. Urgent magnetic resonance imaging and venography (MRI/MRV) of the brain in the ED showed evidence of thrombosis of the superior sagittal sinus extending to the torcular herophili, straight sinus, transverse sinuses, sigmoid sinuses, and proximal internal jugular veins. The precipitating factor for the thrombosis was possibly oral contraceptive pill usage, which she had been taking for a month. She was treated aggressively with anticoagulation. The patient subsequently improved symptomatically and achieved full neurological recovery. In this patient, early recognition of the clinical symptoms and a CT scan with confirmation by MRI/MRV of the brain enabled the prompt diagnosis and treatment of cerebral venous sinus thrombosis with a good clinical outcome.

Myanmarese Neuropathy: Clinical Description of Acute Peripheral Neuropathy Detected among Myanmarese Refugees in Malaysia.

Background. Since 2008, we have observed an increasing number of Myanmarese refugees in Malaysia being admitted for acute/subacute onset peripheral neuropathy. Most of them had a preceding history of starvation. Methods. We retrospectively studied the clinical features of all Myanmarese patients admitted with peripheral neuropathy from September 2008 to January 2014. Results. A total of 24 patients from the Chin, Rohingya, and Rakhine ethnicities (mean age, 23.8 years; male, 96%) had symmetrical, ascending areflexic weakness with at least one additional presenting symptom of fever, lower limb swelling, vomiting, abdominal pain, or difficulty in breathing. Twenty (83.3%) had sensory symptoms. Ten (41.6%) had cranial nerve involvement. Nineteen patients had cerebrospinal fluid examinations but none with evidence of albuminocytological dissociation. Neurophysiological assessment revealed axonal polyneuropathy, predominantly a motor-sensory subtype. Folate and vitamin B12 deficiencies were detected in 31.5% of them. These findings suggested the presence of a polyneuropathy related to nutrition against a backdrop of other possible environmental factors such as infections, metabolic disorders, or exposure to unknown toxin. Supportive treatment with appropriate vitamins supplementation improved functional outcome in most patients. Conclusion. We report a spectrum of acquired reversible neurological manifestations among Myanmarese refugees likely to be multifactorial with micronutrient deficiencies playing an important role in the pathogenesis.