A prospective, observational, multicentre study to evaluate the efficacy of brivaracetam as adjuvant therapy for epilepsy: The Bravo study.

Background: Epilepsy is a persistent tendency to experience epileptic seizures and can lead to various neurobiological disorders, with an elevated risk of premature mortality. This study evaluates the efficacy of brivaracetam adjuvant therapy in patients with epilepsy. Methods: A prospective observational multicentre study that was conducted in Pakistan from March to September 2022, by using a non-probability convenience sampling technique. The population consisted of 543 individuals with a diagnosis of epilepsy for whom adjunctive brivaracetam (Brivera; manufactured by Helix Pharma Pvt Ltd., Sindh, Pakistan) was recommended by the treating physician. The research sample was drawn from various private neurology clinics of Karachi, Lahore, Rawalpindi, Islamabad and Peshawar. Data originating from routine patient visits, and assessments at three study time points, were recorded in the study case report form. Results: Across 18 clinical sites, 543 individuals participated, with a mean age of 32.9 years. The most prescribed dosages were 50 mg BD, followed by 100 mg BD. Notably, brivaracetam combined with divalproex sodium was the most prevalent treatment, followed by brivaracetam with levetiracetam. At both the 14th and 90th day assessments, a significant reduction in seizure frequency was observed, with 63.1% of individuals showing a favourable response by day 90. Treatment-naive individuals exhibited higher rates of seizure freedom and response compared with treatment-resistant individuals. Conclusions: The study demonstrates the effectiveness of brivaracetam combination therapy in epilepsy management, with notable reductions in seizure frequency and favourable clinical responses observed, particularly in treatment-naive individuals.

Correlation of Cerebrospinal Fluid Total Protein and Serum Neutrophil-to-Lymphocyte Ratio with Clinical Outcomes of Guillain-Barre Syndrome Variants.

OBJECTIVE: To evaluate the correlation of cerebrospinal fluid total protein and serum neutrophil-to-lymphocyte ratio with the clinical outcomes and the various clinical and electrophysiological variants of Guillain-Barre syndrome. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: Department of Neurology, Mayo Hospital and King Edward Medical University, Lahore, Pakistan, from November 2022 to April 2023. METHODOLOGY: Fourty-six Guillain-Barre syndrome patients, aged 12-70 years, were included in the study diagnosed by using the Brighton's criteria. Functional disability and respiratory insufficiency were assessed by using the modified Hughes disability score and the Erasmus Guillain-Barre syndrome respiratory insufficiency score, respectively. Serum neutrophil-to-lymphocyte ratio and cerebrospinal fluid total protein were calculated for each patient at the time of admission. RESULTS: Axonal variants had a higher mean neutrophil-to-lymphocyte ratio (5.29 ± 4.38) than demyelinating variants (4.71 ± 3.4) and Miller-Fischer syndrome (3 ± 2.828). This ratio was positively correlated with the modified Hughes's disability score (r = 0.790, p = 0.001) and the Erasmus Guillain-Barre syndrome respiratory insufficiency score (r = 0.936, p = 0.002). Mean cerebrospinal fluid total protein was higher for demyelinating (218 ± 136 mg/dl) than axonal variants (86 ± 56 mg/dl) and Miller-Fischer syndrome (34 ± 21 mg/dl). However, higher modified Hughes disability score (4-6) (r = 0.020, p = 0.117) and a high Erasmus Guillain-Barre syndrome respiratory insufficiency score (5-7) (r = 0.115, p = 0.302) did not significantly affect mean cerebrospinal fluid total proteins. CONCLUSION: Serum neutrophil-to-lymphocyte ratio can be regarded as a reliable biomarker to assess disease severity and clinical outcome in Guillain-Barre syndrome. Cerebrospinal fluid total protein is a poor predictor of the prognosis and severity of Guillain-Barre syndrome. KEY WORDS: Guillain-Barre syndrome (GBS), Clinical outcome, Cerebrospinal fluid total protein (CSF-TP), Neutrophil-to-lymphocytic ratio (NLR), Prognostic biomarker.

Fahr's syndrome as a manifestation of autoimmune polyendocrine syndrome-1 and its unusual association with neuromyelitis optica spectrum disorder.

Fahr's syndrome, also known as bilateral striopallidodendate calcinosis, is a rare inherited neurodegenerative illness characterized by abnormal calcium deposition in several areas of the brain, resulting in a wide range of neuropsychological symptoms. Fahr's syndrome, secondary to autoimmune polyendocrine syndrome type 1, which includes adrenal insufficiency and mucocutaneous candidiasis in addition to hypoparathyroidism, is exceedingly rare. No case report has been documented to date to show the co-occurrence of Fahr's syndrome and neuromyelitis optica spectrum disorder. Here, we discuss the case of a 30-year-old man with a previous history of seizures and symptoms of ectodermal dystrophy presented with seizures, left-sided hemiparesis, dysarthria, and other characteristics indicative of severe hypocalcemia. The neuroimaging findings strongly suggested Fahr's syndrome, with radiographic evidence of Neuromyelitis optica spectrum disorder as longitudinal extensive transverse myelitis in the cervical spinal cord, high titers of serum aquaporin-4 antibodies, and demyelinating neuropathy on nerve conduction studies. This distinct neuropsychological presentation and neuroimaging findings led to the diagnosis of Fahr's syndrome as a result of hypoparathyroidism caused by autoimmune polyendocrine syndrome type 1 with cooccurrence of neuromyelitis optica spectrum disorder. The patient's clinical symptoms improved considerably after he was treated based on a provisional diagnosis. The clinical importance of our case is significant for both neuropsychiatrists and endocrinologists, as autoimmune polyendocrine syndrome should be considered as the etiology of Fahr's syndrome. This case report also aims to report this unusual association of Neuromyelitis optica spectrum disorder with Fahr's syndrome to give the future prospective to know whether this association is incidental or there is a missing link between these two different disorders.

Neuropathy following intramuscular injections: a clinical and neurophysiological study from a tertiary care centre in Pakistan.

OBJECTIVE: To assess the clinical and neurophysiological profile of peripheral nerve injuries in patients following intramuscular injections. METHODS: The descriptive, cross-sectional study was conducted at the Department of Neurology, Mayo Hospital, Lahore, Pakistan, from July 2019 to January 2021, and comprised adult patients of either gender with isolated peripheral nerve injuries following intramuscular injections. Nerve conduction studies were performed for each patient. Data was analysed using SPSS 26. RESULTS: Of the 99 patients, 59(59.6%) were males and 40(40.4%) were females. The mean age was 26.7+/-18.1 years, 34(34.3%) patients were under weight and 78(78.8%) were either illiterate or had low literacy level. Radial nerve was involved in 56(56.6%) cases, followed by sciatic in 39(39.4%) and axillary nerve 4(4.04%). Overall, 14(14.14%) injection had been administered by doctors, while the other 85(85.85%) were given by paramadics. Marked reduction in compound muscle action potential 72(72.7%) and sensory nerve action potential 82(82.8%) was noted, while re-innervation was seen in 78(78.7%). CONCLUSIONS: Intramuscular nerve injuries can be greatly minimised by spreading awareness regarding safe injection techniques and strict implementation of standard operating procedures in hospitals and clinics.

Non-Motor Symptoms Burden in Early Stages of Parkinson's Disease.

Background: Non-motor symptoms (NMSs) in Parkinson's disease (PD) are often overlooked and thus can impede clinical management and significantly reduce the patient's quality of life. Aims: The study aimed to determine the burden of NMS in the early stages of PD. Material and Methods: A 1-year observational cross-sectional study was conducted at Mayo Hospital, Lahore, in 2019. The MDS-PD criteria were used to diagnose PD patients. The study included patients with Hoehn and Yahr (HY) stages 1-3. The frequency of NMSs was assessed using a non-motor symptom questionnaire (NMSQ), and the non-motor symptom scale (NMSS) score was derived using the NMSS. Results: A total of 100 PD patients were enrolled in the study. Sixty-three (63%) were males and 37 (37%) were females. Their age ranged between 45 and 75 years with a mean ± SD of 57.46 ± 8.46. At least one NMS was reported by 84% of patients, with neuropsychiatric symptoms (68%) preponderant, followed by a change in taste and smell (64%). The mean NMSS score is 46.22 ± 22.098 (median 44) with a range from 0 to 88, with the trend being increasing score with the advancing stage. Conclusion: The use of the NMSQ and NMSS tools should be standard in clinical practice to identify the severity of the disease and commence appropriate care.

A Case Report and Literature Review of the Outcome of Linezolid-Induced Optic and Peripheral Neuropathy in Patients With Multidrug-Resistant Pulmonary TB.

Linezolid is a second-line medication used to treat tuberculosis that has become resistant to multiple drugs. Linezolid has been shown to be effective in treating drug-resistant TB. However, long-term therapy is hampered by the related side effects, such as ocular and peripheral neuropathy. We recently encountered a 32-year-old male undergoing linezolid therapy for 12 months for multidrug-resistant tuberculosis who presented with progressive painless visual impairment and peripheral neuropathy symptoms in lower limbs as well as ataxic gait. Nerve conduction study findings of length-dependent axonal sensory polyneuropathy with bilateral optic neuropathy evident on fundoscopy suggested a case of toxic neuropathy. Following the termination of linezolid, follow-up visits revealed an improvement in visual symptoms. While there has been no discernible improvement or deterioration of peripheral neuropathy. In a developing country like Pakistan, where the rising number of cases of multidrug-resistant tuberculosis and its management is a major problem, physicians should be made aware of linezolid induced neuropathy so that close follow-up sessions for patients on long-term linezolid therapy can be arranged to avoid serious neurological consequences.

Susceptibility pattern of Mycobacterium tuberculosis over a period of five years at Indus Hospital and Health Network, Karachi, Pakistan.

Objective: To determine the susceptibility pattern and frequency of isolation of multidrug, pre-extensively drug and extensively drug resistant TB in a tertiary care hospital in Karachi, Pakistan. Method: A cross-sectional study was designed. Samples received in the lab were processed for growth and sensitivity testing of Mycobacterium tuberculosis. Isolation of MTB was done on Mycobacteria growth indicator tube (MGIT) followed by identification using MPT64. Samples were than evaluated for drug sensitivity against first and second-line antimycobacterial drugs. Statistical analysis was performed using SPSS version 24.0. Results: Of the 20014 samples received, 23.1% were identified as Mycobacterium tuberculosis. Drug sensitivity testing was performed on 95.9% isolates. Fifty-two percent samples were from males and 48% female patients. The study found statistically non-significant relationship between gender and likelihood of disease with drug-resistant (DR)-MTB organisms. The rate of isolation of MDR-TB was highest (43%) among ages 25-55 years and previously treated patients compared to newly diagnosed patients (62% vs 36%). Among MTB positive samples, 91.5% were pulmonary while 8.5% were extrapulmonary samples. Extrapulmonary samples were more likely to be sensitive to antimycobacterial drugs. The highest resistance was observed against Isoniazid (pulmonary=58%; extrapulmonary=12.7%), Rifampicin (pulmonary=58.7%; extrapulmonary=8.2%), and Levofloxacin (pulmonary=29.2%; extrapulmonary=20%). Conclusion: A considerable number of drug resistant tuberculosis cases were identified in the present study. It is essential to develop further strategies to reduce the spread of this disease.

Gradenigo's syndrome presenting as IX and X cranial nerve palsy without clinically apparent ear infection: A case report and review of literature.

Gradenigo's syndrome (GS) is a triad (otorrhea, abducens nerve palsy, and pain in the trigeminal nerve distribution) of clinical findings that are caused by contiguous spread of petrous apicitis to the nearby neurovascular structures. Petrous apicitis is usually secondary to otitis media but atypical etiologies and absence of the classical triad pose a diagnostic challenge for physicians. We report a rare case of GS in an afebrile 55-year-old male who presented with unilateral headache, dysphagia and hoarseness (IX and X cranial nerve involvement), and diplopia with lateral gaze palsy (VI nerve involvement) in the absence of trigeminal neuralgia or a history of otitis media. Magnetic Resonance Imaging (MRI) revealed hyperintense lesions in the right petrous apex indicating petrous apicitis, the hallmark of GS. Prompt initiation of broad-spectrum antibiotics led to a marked improvement in dysphagia and voice quality on the 4th post-admission day, and complete resolution of symptoms by the end of the fourth week. This shows that GS can present even in the absence of clinically apparent ear infection and cranial nerve palsies may not be limited to the V and VI nerve in all cases. Physicians should be aware of such atypical manifestations as prompt radiological assessment followed by early antibiotics can prevent life-threatening complications from developing.

Structural Imaging Characteristic, Clinical Features and Risk Factors of Cerebral Venous Sinus Thrombosis: A Prospective Cross-Sectional Analysis from a Tertiary Care Hospital in Pakistan.

Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke that accounts for 0.5-1.0% of all strokes. Clinical presentation, predisposing factors, neuroimaging findings, and outcomes of CVST are extremely diverse, which causes a high index of suspicion in diagnosis. Therefore, early diagnosis of CVST is crucial for prompt treatment to prevent morbidity and mortality. OBJECTIVE: The purpose of this prospective study is aimed at assessing the clinical characteristics, potential risk factors, and neuro-radiological features along with the topography of venous sinus involved in CVST patients in a tertiary care hospital, Lahore, Pakistan. MATERIAL AND METHODS: Consecutive patients enrolled in this study had a computed tomography (CT) scan, magnetic resonance imaging (MRI), and magnetic resonance venography (MRV) along with a clinical presentation to confirm the diagnosis of CVST. Categorical data were presented as percentages. Continuous variable and categorical data were compared (parenchymal lesions vs. non-parenchymal lesions) using the Student's t-test and Chi-square test, respectively. RESULTS: A total of 3261 patients with stroke were presented during the study period. Out of all patients, 53 confirmed patients with CVST (1.6%) were recruited; the predominant population was female (84.91%), having a male to female ratio of 1:4. Mean age of the cohort was 28.39 ± 7.19 years. Most frequent symptoms observed were headache (92.45%) followed by vomiting (75.47%), seizures (62.26%), papilledema (54.72%), visual impairment (41.51%), and altered consciousness disturbance (52.83%). The presumed risk factors associated with CVST were puerperium (52.83%), use of oral contraceptives (13.21%), antiphospholipid syndrome (7.55%), elevated serum levels of protein C and S (5.66%), and CNS infection (3.77%). On cranial CT scans, 50 patients (94.33%) showed abnormalities while 32 patients exhibited various parenchymal lesions. Seizures were more frequent in CVST patients with parenchymal lesions compared with subjects lacking parenchymal lesions. Seventy-two sinuses, either single or in combination, were involved in CVST patients, being more common in patients with parenchymal lesions than those without parenchymal lesions. The most frequent locations of CVST were the superior sagittal and transverse sinus. CONCLUSION: In short, non-contrast CT brain may be used as a first line investigation in suspected cases of CVST. Our study also demonstrates some regional differences in the clinical features, risk factors, and neuroimaging details of CVST as described by some other studies. Therefore, care must be taken while diagnosing and predicting the outcome of the CVST.

Evaluation of GenoType MTBDRplus for the detection of drug-resistant Mycobacterium tuberculosis on isolates from Karachi, Pakistan.

OBJECTIVE: To compare the diagnostic performance of the GenoType MRBDRplus assay with the gold standard phenotypic drug susceptibility testing in the detection of drug resistance among culture isolates obtained from patients in Karachi, Pakistan. DESIGN: Mycobacterium tuberculosis isolates were obtained from 96 consecutive tuberculosis patients found to have resistance to isoniazid from two health centers in Karachi (January-November 2017). Isolates were tested for drug resistance against rifampin and isoniazid using the MTBDRplus assay. Results were compared with conventional drug-susceptibility testing and the frequency of specific mutations were reported. RESULTS: The MTBDRplus assay had a sensitivity for rifampin resistance of 98.8% (95% CI: 93.4-100) and for isoniazid resistance of 90.6% (95% CI: 83.0-95.6). The MTBDRplus assay showed mutations in rpoB in 81 of the 96 (84.4%) isolates. Of the 87 isolates showing resistance to isoniazid via the MTBDRplus assay, 71 (74.0%) isolates had mutations in the katG gene only, 15 (15.6%) isolates had mutations in the inhA promoter region, and 1 (1.0%) showed mutations in both genes. CONCLUSION: The GenoType MTBDRplus assay in Pakistan can identify subgroups at high-risk of having isolates with mutations in the katG and/or inhA genes. Understanding the local burden of these mutations have implications for local diagnostic and treatment guidelines.