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.

Brait-Fahn-Schwartz Disease: A Unique Co-Occurrence of Parkinson's Disease and Amyotrophic Lateral Sclerosis.

The Parkinson's disease-amyotrophic lateral sclerosis (ALS) complex typically manifests as levodopa-responsive parkinsonism, followed by ALS. It is extremely rare for Parkinson's disease and ALS to coexist without other neurological disorders. Named after the scientists who first described this overlap of two neurodegenerative conditions, it is referred to as Brait-Fahn-Schwartz disease. Given its variable presentation, increasing rarity, and lack of any diagnostic test, it poses a diagnostic challenge for physicians. We present a case of a 55-year-old Pakistani male experiencing progressive quadriparesis with spastic lower limbs and flaccid upper limbs, in addition to the cardinal features of idiopathic Parkinson's disease. Since there is currently no cure available for either Parkinson's disease or ALS, all available treatment focuses on improving quality of life, which we achieved in our patient. This case is unique in being the first incidence of Parkinson's disease-ALS complex in a novel geographic region such as Pakistan, where genetic testing and cost constraints limit the diagnosis of rare disorders. The coexistence of extrapyramidal symptoms and pyramidal symptoms is uncommon. In such situations, physicians may overlook one group of symptoms, potentially leading to a misdiagnosis. This case highlights the value of a thorough physical examination and electrodiagnostic studies and suggests the association between Parkinson's disease and ALS. This case demonstrates the significance of understanding when Parkinson's disease symptoms start to appear in patients with ALS and the need to start dopaminergic therapy in those who had Parkinson's disease features before ALS to alleviate the suffering of an individual and enhance quality of life.

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.

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.

Efficacy and Safety of Brivaracetam in Persons With Epilepsy in a Real-World Setting: A Prospective, Non-Interventional Study.

BACKGROUND AND AIM: Epilepsy stands out as one of the most prevalent neurological conditions. Brivaracetam (BRV) is a noteworthy antiseizure medication (ASM) distinguished by its pronounced and selective interaction with the synaptic vesicle protein 2A (SV2A) within the brain. Prior investigations, including regulatory trials, post-marketing assessments, and comparative meta-analyses, have consistently underscored BRV's equivalency in efficacy and superior tolerability when pitted against other antiseizure drugs. This study aimed to evaluate the effectiveness, safety, and acceptability of BRV in treating epileptic patients in the Pakistani population. METHODS: This prospective observational study, conducted in Pakistan from February to December 2022, employed a non-probability consecutive sampling technique. This study included 368 adult patients diagnosed with epilepsy, with a focus on those aged 18 and above experiencing focal seizures. Demographic data, clinical history, seizure types, and epilepsy profiles were recorded. Patients were administered BRV (Brivera; manufactured by Helix Pharma Pvt Ltd., Sindh, Pakistan) monotherapy therapy under physician guidance and followed up for three months. The study assessed changes in seizure frequency, side effects, and drug resistance at baseline, 14th day, and 90th day. Safety aspects were monitored, including documenting any adverse effects associated with BRV therapy. RESULTS: A total of 368 epileptic patients were included in this study, of which 287 (61.3%) were males and 181 (38.7%) were females. The mean age was 32.91±17.11 years. The mean number of seizures at the baseline visit was 5.74±6.21, at 14 days was 2.89±3.84 and at 90 days was 1.73±5.01 (p<0.001). Overall, a more than 50% reduction in seizure episodes was achieved in 178 (56.3%) patients at day 90, and less than 50% reduction in seizure episodes was achieved by 95 (26.8%) patients on Day 14, with a highly significant association between them (p<0.001). Among 316 patients, only 41 (4.4%) of all BRV-treated patients experienced adverse events; Of these 41 patients, 17 (41.7%) reported dizziness and 14(34.2%) reported behavioral issues. CONCLUSIONS: Epileptic patients receiving BRV demonstrated a substantial reduction of greater than 50% seizure episodes at the end of follow-up visits. Moreover, BRV exhibited fewer adverse effects in individuals with epilepsy.

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.

Clinical and biochemical indicators of disease severity and neurological findings in COVID-19: A study of King Edward Medical University (KEMU), Pakistan.

This study investigated the significance of difference between presence and absence of different neurological findings in COVID-19, in relation with the biochemistry. Various significant correlations in connection with the disease severity and clinical factors were also identified. 351 COVID-19 patients were included. Different laboratory/ clinical findings were investigated. Correlations Kendall's tau and Pearson Chi-Square were applied to find the correlations between severity and clinical findings. The Mann-Whitney Test was applied for a comparison between two types of neurological groups for each biochemistry parameter. Headache was reported in 28% and dizziness in 13% patients. The impaired smell and impaired taste were reported in 28.5% and 36.2% patients, respectively. The muscle pain was present in 39% patients. 80% patients had low lymphocytes & 70% had high neutrophils. 54.5% were found with high ALP. LDH was elevated in 73%. Severity was found significantly correlated with decreased oxygen saturation, age and raised levels of urea, creatinine and LDH. The groups (with/without CNS involvement) were statistically different in ALP, groups (with/without PNS involvement) in WBC, lymphocytes, neutrophils, ALP, urea, creatinine, CK, CKMB and LDH and groups (with/without MSK involvement) in WBC. Oxygen saturation, age, urea, creatinine and LDH are significant indicators of disease severity in COVID-19. The altered levels of different biochemistry can impact the neurological states of COVID-19 patients.

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.

Correlation between Testicular Hemodynamic and Semen Quality Indices in Clinical Varicocele Patients in Pakistan.

Varicocele, a vascular event, is associated with infertility due to testicular damage that causes abnormal spermatogenesis in males. The goal of this study is to ascertain the diagnostic significance of scrotal color Doppler ultrasonography (CDUS) by measuring peak systolic value (PSV) and resistive index (RI) of the arteries supplying blood to the testis and their association with semen quality attributes. Sixty prospective patients (age: 20-50 years) undergoing microsurgical varicocelectomy at a teaching hospital were included in the study. Semen parameters and CDUS were recorded and testicular blood flow was determined as PSV and RI of subcapsular artery and intraparenchymal artery of the testes. Nonparametric statistics was applied to test the correlation/association of the semen quality with the PSV, RI, and other variables. Results revealed a significant negative correlation (r = -0.28; p < 0.05) between progressive motility of spermatozoa and resistive index of the intraparenchymal arterial blood flow. Furthermore, it was noticed that the progressive motility of spermatozoa was tended to be negatively correlated (r = -0.236) with resistive index of subcapsular arterial blood flow. In conclusion, this study has revealed that progressive motility of sperms has correlation with the intraparenchymal blood flow of testes. The progressive motility of sperms could be correlated with RI of testicular blood flow. The apparent lack of association between diameter of varicocele vein and semen quality signifies the need of investigating some other factors that may be involved in pathogenicity of varicocele. The diagnostic value of CDUS may be carefully interpreted and clinically correlated in assessment of severity of varicocele.

Pattern of varicocele vein blood gases in patients undergoing microsurgical Varicocelectomy.

BACKGROUND: Varicocele is known to be associated with infertility and sperm disorders. The exact cause of this ailment is not fully understood. There are limited numbers of studies where venous blood gases (VBGs) of varicocele veins were determined with conflicting results. Therefore, we have investigated the pattern of VBGs in both internal spermatic and external spermatic varicocele veins and correlation with semen quality parameters in infertile individuals who underwent left microsurgical varicocelectomy. METHODS: Patients (n = 27) undergoing left microsurgical varicocelectomy at a tertiary care hospital, were included in the study. Before surgery, semen parameters and scrotal color Doppler ultrasonography was performed. During surgery, blood sample was drawn from varicocele veins (internal spermatic and external spermatic veins) and a peripheral arm vein of the same patient as a control. The VBGs of all veins under study were estimated and compared with each other. The VBGs were also correlated with various semen quality parameters. Data, expressed as Mean ± SD, regarding VBGs in three veins were analyzed using one-way ANOVA. The correlation between VBGs and semen quality parameters was determined using Pearson's correlation. Differences were considered significant at p < 0.05. RESULTS: The pH was found to be higher (p < 0.01) in the internal spermatic vein compared with the external spermatic and the peripheral veins. Partial pressure of oxygen (pO2) and oxygen saturation (sO2) were higher (p < 0.01) in the internal spermatic vein compared with the peripheral vein. However, concentration of bicarbonate (HCO3) was lower (p < 0.01) in both veins compared with the peripheral vein. Partial pressure of carbon dioxide (pCO2) was also lower (p < 0.01) in the varicocele veins compared with the control vein. CONCLUSION: The internal spermatic veins had higher pH and oxygen tension, but lower HCO3 and pCO2 levels compared with the control peripheral veins. External spermatic veins had lower pCO2 and HCO3 but other VBGs were similar to the peripheral veins. The shift of VBGs of internal spermatic vein toward arterial blood pattern may be a missing link to understand the pathophysiology of varicocele.

WITHDRAWN: Venous Blood Gases of Varicocele Veins: Correlation With Testicular Blood Flow and Semen Quality in Varicocele Patients.

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PERFORMANCE OF TWO DIFFERENT CLINICAL SCORING SYSTEMS IN DIAGNOSING DISTAL SENSORY POLYNEUROPATHY IN PATIENTS WITH TYPE-2 DIABETES.

BACKGROUND: Early diagnosis of distal peripheral neuropathy (DSPN) the commonest diabetes complications, helps prevent significant morbidity. Clinical parameters are useful for detection, but subjectivity and lack of operator proficiency often results in inaccuracies. Comparative diagnostic accuracy of Diabetic Neuropathy Symptom (DNS) score and Diabetic Neuropathy Examination (DNE) score in detecting DSPN confirmed by nerve conduction studies (NCS) has not been evaluated. This study compares the performance of these scores in predicting the presence of electro physiologically proven DSPN. The objective of this, study was to compare the diagnostic accuracy of DNS and DNE scores in detecting NCS proven DSPN in type-2 diabetics, and to determine the frequency of sub-clinical DSPN among type-2 diabetics. METHODS: In this cross-sectional study the DNS score and DNE score were determined in 110 diagnosed type-2 diabetic patients. NCS were carried out and amplitudes, velocities and latencies of sensory and motor nerves in lower limb were recorded. RESULTS: Comparison between the two clinical diagnostic modalities and NCS using Pearson's chi square test showed a significant association between NCS and DNE scores (p-value =.003, specificity 93%). The DNS score performed poorly in comparison (p-value = .068, specificity 77%). When the two scores were taken in combination the specificity in diagnosing DSPN was greater (p-value = .018, specificity 96%) than either alone. 33% of patients had subclinical neuropathy. CONCLUSION: DNE score alone and in combination with DNS score is reliable in predicting DSPN and is more specific than DNS score in evaluating DSPN. Both tests lack sensitivity. Patients without any evidence of clinical neuropathy manifest abnormalities on NCS.