Cognitive therapy for depression in tuberculosis treatment: protocol for multicentre pragmatic parallel arm randomised control trial with an internal pilot.

INTRODUCTION AND OBJECTIVES: There is an unmet need to develop high-quality evidence addressing tuberculosis (TB)-related mental health comorbidity, particularly in the context of lower-middle-income countries. This study aims to examine the effectiveness and cost-effectiveness of cognitive behavioural therapy (CBT) versus enhanced treatment as usual (ETAU) in improving depressive symptoms in people with TB and comorbid depression, enhancing adherence with anti-TB treatment (ATT) and its implementation in the real-world setting of Pakistan. METHODS: We will conduct a pragmatic parallel arm randomised control trial with an internal pilot. A brief psychological intervention based on CBT has been developed using a combination of qualitative and ethnographic studies. The inbuilt pilot trial will have a sample size of 80, while we plan to recruit 560 (280 per arm) participants in the definitive trial. Participants who started on ATT within 1 month of diagnosis for pulmonary and extrapulmonary TB or multidrug resistant TB (MDR-TB) and meeting the criteria for depression on Patient Health Questionnaire-9 (PHQ-9) will be randomised with 1:1 allocation to receive six sessions of CBT (delivered by TB healthcare workers) or ETAU. Data on the feasibility outcomes of the pilot will be considered to proceed with the definitive trial. Participants will be assessed (by a blinded assessor) for the following main trial primary outcomes: (1) severity of depression using PHQ-9 scale (interviewer-administered questionnaire) at baseline, weeks 8, 24 and 32 postrandomisation and (2) ATT at baseline and week 24 at the end of ATT therapy. ETHICS AND DISSEMINATION: Ethical approval has been obtained from Keele University Research Ethics Committee (ref: 2023-0599-792), Khyber Medical University Ethical Review Board (ref: DIR/KMU-EB/CT/000990) and National Bioethics Committee Pakistan (ref: No.4-87/NBC-998/23/587). The results of this study will be reported in peer-reviewed journals and academic conferences and disseminated to stakeholders and policymakers. TRIAL REGISTRATION NUMBER: ISRCTN10761003.

Mitochondrial neurogastrointestinal encephalomyopathy in a Pakistani female: a case report.

BACKGROUND: Mitochondrial neurogastrointestinal encephalopathy is a rare multisystem autosomal recessive disease caused by mutations in the TYMP gene, that encodes for thymidine phosphorylase. Mitochondrial neurogastrointestinal encephalopathy is a progressive degenerative disease characterized by a distinctive tetrad of gastrointestinal dysmotility, peripheral neuropathy, ophthalmoplegia with ptosis, and asymptomatic leukoencephalopathy. It provides a diagnostic dilemma to physicians in regions like Pakistan because of a lack of genetic study availability and associated financial constraints of the population. However, with careful examination and a few basic investigations, mitochondrial neurogastrointestinal encephalopathy can be diagnosed by ruling out most of the close differentials. CASE PRESENTATION: We report the case of a 23-year-old Asian female whose chief complaints were epigastric pain, bilious emesis, weight loss for 3 months, and bilateral lower limb weakness for 20 days. All clinical signs and symptoms along with relevant investigations including nerve conduction studies, electromyography, and magnetic resonance imaging of the brain were highly suggestive of mitochondrial neurogastrointestinal encephalopathy syndrome. Because of financial constraints, genetic studies could not be performed. The patient was managed with a multidisciplinary approach involving gastroenterology, physiotherapy, and nutrition departments. Currently, therapeutic options for the disease include allogeneic hematopoietic stem cell transplant and carrier erythrocyte entrapped thymidine phosphorylase; however, these could not be provided to the patient owing to certain limitations. CONCLUSIONS: As misdiagnosis and delayed diagnosis are quite common in this disease, the prime objective of this case report is to increase the basic understanding of this disease, especially its signs and symptoms, and address the limitations regarding the diagnostic investigations and management of patients with mitochondrial neurogastrointestinal encephalopathy.

Anti-leucine-rich-glioma-inactivated 1 Limbic Encephalitis: An Underrecognised Disease.

Autoimmune limbic encephalitis is a rare autoimmune disease characterised by inflammation of the limbic system of the brain. The disease runs a sub-acute course with cognitive impairment, memory loss and seizures. These patients have been underdiagnosed in Pakistan. Here, we present a case of a middle-aged male, who presented to our Department after having multiple visits to different psychiatrists for his symptoms. The patient had been put on multiple psychiatric and antiepileptic medications, but his condition gradually declined. At our Department, he was thoroughly assessed and then diagnosed as limbic encephalitis on the basis of the typical history, positive anti-leucine-rich-glioma-inactivated 1 (LGI1) antibodies and MRI findings. The patient responded to plasmapheresis and immune modulating therapy and is being followed up. Emphasis is made on early diagnosis; and earlier treatment of such cases, as it holds a substantial importance in management and makes a difference in future outcome. Key Words: Autoimmune limbic encephalitis, Voltage-gated potassium channels, Cognitive dysfunction.

Post-COVID Opsoclonus Myoclonus Syndrome: A Case Report From Pakistan.

Background: Coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory distress syndrome-coronavirus-2 (SARS-CoV-2), is primarily a respiratory infection but has been recently associated with a variety of neurological symptoms. We present herewith a COVID-19 case manifesting as opsoclonus-myoclonus syndrome (OMS), a rare neurological disorder. Case Presentation: A 63-year-old male diagnosed with COVID-19 infection developed behavioral changes, confusion, and insomnia followed by reduced mobility and abnormal eye movements within 48 h of recovery from respiratory symptoms associated with COVID-19. On examination, he had rapid, chaotic, involuntary saccadic, multidirectional eye movements (opsoclonus), and limb myoclonus together with truncal ataxia. CSF analysis, MRI of the brain, and screening for anti-neuronal and encephalitis related antibodies were negative. Extensive testing revealed no underlying malignancy. The patient was successfully treated with intravenous immunoglobulin (IVIG) with complete resolution of symptoms within 4 weeks of treatment. Conclusion: COVID-19 infection can be associated with the manifestation of opsoclonus myoclonus syndrome, a rare neurological disorder that can be treated with IVIG if not responsive to corticosteroids.

Crossed Cerebellar Diaschisis In A Child With Status Epilepticus: An Unusual Presentation.

Crossed Cerebellar Diaschisis (CCD) describes a depression of oxidative metabolism and blood flow in the cerebellum secondary to a supratentorial lesion in the contralateral cerebral hemisphere. The pathophysiology is not clear but appears to be caused by abnormal neuronal connection of the primary to the remote site. The diagnosis is usually done using positron emission tomography (PET) and singlephoton emission CT (SPECT) scans. Almost all the reported cases of CCD are caused by acute ischemic stroke in adults. Hence, CCD secondary to status epilepticus, extremely rare and there is limited literature available on it. This is important because it's findings can easily be confused with acute ischemic stroke and similar concurrent diseases. Correct diagnosis can also help localize the cause of the seizures and significantly influence surgical decisions. We present a case of CCD in a child with status epilepticus using MRI of the brain with DWI.

Supervised treatment in outpatients for schizophrenia plus (STOPS+): protocol for a cluster randomised trial of a community-based intervention to improve treatment adherence and reduce the treatment gap for schizophrenia in Pakistan.

INTRODUCTION: There is a significant treatment gap, with only a few community-based services for people with schizophrenia in low-income and middle-income countries. Poor treatment adherence in schizophrenia is associated with poorer health outcomes, suicide attempts and death. We previously reported the effectiveness of supervised treatment in outpatients for schizophrenia (STOPS) for improving treatment adherence in patients with schizophrenia. However, STOPS was evaluated in a tertiary care setting with no primary care involvement, limiting its generalisability to the wider at-risk population. We aim to evaluate the effectiveness of STOPS+ in scaling up the primary care treatment of schizophrenia to a real-world setting. METHODS AND ANALYSIS: The effectiveness of the STOPS+ intervention in improving the level of functioning and medication adherence in patients with schizophrenia in Pakistan will be evaluated using a cluster randomised controlled trial design. We aim to recruit 526 participants from 24 primary healthcare centres randomly allocated in 1:1 ratio to STOPS+ intervention and enhanced treatment as usual arms. Participants will be followed-up for 12 months postrecruitment. The sample size is estimated for two outcomes (1) the primary clinical outcome is level of functioning, measured using the Global Assessment of Functioning scale and (2) the primary process outcome is adherence to treatment regimen measured using a validated measure. An intention-to-treat approach will be used for the primary analysis. ETHICS AND DISSEMINATION: Ethical approval has been obtained from Keele University Ethical Review Panel (ref: MH-190017) and Khyber Medical University Ethical Review Board (ref: DIR-KMU-EB/ST/000648). The results of the STOPS+ trial will be reported in peer-reviewed journals and academic conferences and disseminated to local stakeholders and policymakers. TRIAL REGISTRATION NUMBER: ISRCTN93243890.

Greedy Successive Anchorization for Localizing Machine Type Communication Devices.

Localization of machine type communication (MTC) devices is essential for various types of location-based applications. In this paper, we investigate a distributed localization problem in noisy networks, where an estimated position of blind MTC machines (BMs) is obtained by using noisy measurements of distance between BM and anchor machines (AMs). We allow positioned BMs also to work as anchors that are referred to as virtual AMs (VAMs) in this paper. VAMs usually have greater position errors than (original) AMs, and, if used as anchors, the error propagates through the whole network. However, VAMs are necessary, especially when many BMs are distributed in a large area with an insufficient number of AMs. To overcome the error propagation, we propose a greedy successive anchorization process (GSAP). A round of GSAP consists of consecutive two steps. In the first step, a greedy selection of anchors among AMs and VAMs is done by which GSAP considers only those three anchors that possibly pertain to the localization accuracy. In the second step, each BM that can select three anchors in its neighbor determines its location with a proposed distributed localization algorithm. Iterative rounds of GSAP terminate when every BM in the network finds its location. To examine the performance of GSAP, a root mean square error (RMSE) metric is used and the corresponding Cramér-Rao lower bound (CRLB) is provided. By numerical investigation, RMSE performance of GSAP is shown to be better than existing localization methods with and without an anchor selection method and mostly close to the CRLB.

Barr humbug: acute cerebellar ataxia due to Epstein-Barr virus.

Epstein-Barr virus (EBV) infection is associated with neurological sequellae, but rarely there is acute cerebellar ataxia (ACA) in an adult. We present a novel case of a 26-year-old man, who presented with ACA. He had normal MRI and CSF analysis. Serum testing confirmed active EBV. A course of oral prednisolone 1 mg/kg for 4 weeks, with a subsequent taper was started. He made a full recovery within 3 weeks of presentation.

Myasthenia gravis as a 'stroke mimic'--it's all in the history.

An 85-year-old man presented to hospital as an emergency having difficulties with swallowing and speech. In the emergency department, he was assessed as having acute onset dysphagia and dysarthria in keeping with an acute stroke. Subsequently, it became apparent that although the symptoms were indeed of relatively acute onset, there was a clear description by the patient of fatigability and diurnal variation, prompting a working clinical diagnosis of myasthenia gravis. The patient followed a turbulent clinical course, and interpretation of investigation results proved not to be straightforward in the acute setting. Myasthenia gravis is an uncommon disorder but it is more common in the elderly. This case provides key learning points, particularly highlighting the value of prompt, accurate clinical assessment and the importance of adhering to the clinical diagnostic formulation.

Efficacy of endoscopic third ventriculostomy in non-communicating hydrocephalus.

BACKGROUND: Hydrocephalus is common problem requiring either extra-cranial (shunts) or intracranial (ventriculostomy) diversion of cerebrospinal fluid. Endoscopic third ventriculostomy obviates all the complications of shunts and has been accepted as the procedure of choice for the treatment of obstructed hydrocephalus in adults and children because of the minimally invasive nature. This study was conducted to determine the efficacy of endoscopic third ventriculostomy in the treatment of non-communicating hydrocephalus. METHODS: This cross sectional descriptive study was done in neurosurgery department of Hayatabad Medical Complex, Peshawar, from 2nd February 2011 to 1st march 2012. A total of 171 patients with non-communicating hydrocephalous, irrespective of gender discrimination and Glasgow coma scale score of 10 and above were included in this study. Patients below one year of age, with lesion in the floor of the third ventricle or near basilar artery, and hydrocephalus with infected CSF or haemorrhage were excluded. Hydrocephalous was diagnosed on CT-scan brain. All the patients were followed up till 72 hours post-operatively for the determination of effectiveness in terms of improvement in Glasgow coma scale by at least 2 points. All the above mentioned information including name, age, gender and address were recorded in a predesigned proforma. The data was analysed using SPSS-17. Frequency and percentage was calculated for categorical variables. Mean +/- SD was calculated for age. RESULTS: A total of 171 patients with non-communicating hydrocephalous were included in the study. Out of 171 patients, there were 104 (60.8%) males and 67 (39.2%) females. Age ranged from 1-70 years with majority of the patients was below 10 years of age. Majority of the patients had hydrocephalus due to tuberculous meningitis 39.2% of the whole. In 134 (78.4%) patients the procedure was effective. Procedure was more effective in hydrocephalus due to space occupying lesion. CONCLUSION: Endoscopic third ventriculostomy is a very effective procedure for the treatment of non-communicating hydrocephalus.

Experience of extracorporeal shockwave lithotripsy for kidney and upper ureteric stones by electromagnetic lithotriptor.

BACKGROUND: Extracorporeal Shock Wave Lithotripsy (ESWL) is a non-invasive treatment of urinary stones which breaks them, by using externally applied, focused, high intensity acoustic pulse, into smaller pieces so that they can pass easily through ureter. Shock wave generation, focusing, coupling and stone localisation by fluoroscope or ultrasound are the basic components of ESWL. ESWL has some complications and is contraindicated in certain situations. The aim of this study was to evaluate the effectiveness and safety of ESWL in kidney and upper ureteric stones by Electromagnetic Lithotriptor. METHODS: All adult patients with renal and upper ureteric stones having a diameter of up to 1 Cm were included in the study. Basic evaluation such as history, examination, ultrasound and excretory urography were performed. Electromagnetic lithotripsy was done and data were collected on a printed proforma from 1st January 2008 to 30th March 2009 in Institute of Kidney Diseases, Peshawar. RESULTS: Out of a total of 625 patients 463 were male and 162 were female; 67.36% of patients were having renal stones, 23.84% upper ureteric and 8.8% both renal and ureteric stones. Complications noted were renal colic in 9.76%, haematuria in 3.2%, steinstrasse in 2.72%, and fever in 1.12% of patients. The stone free rate was 89% and 7% of patients were having stone fragments <4 mm. ESWL failed in 4% of patients. CONCLUSION: ESWL is a safe and effective way of treating kidney and upper ureteric stones.