Effectiveness and tolerability of repetitive transcranial magnetic stimulation for preventive treatment of episodic migraine: a single-centre, randomised, double-blind, sham-controlled phase 2 trial (Magnet-EM).

BACKGROUND: This is a phase II randomised, double-blind, sham-controlled trial to evaluate the effectiveness and tolerability of repetitive transcranial magnetic stimulation for preventive treatment of episodic migraine amongst migraine subjects. METHODS: Subjects age 18 to 60 years will undergo a baseline evaluation to establish the diagnosis of migraine based on the International Classification of Headache Disorder 3rd Edition (ICHD-3). Those who fulfil the ICHD-3 criteria for episodic migraine and compliant to the headache diary during a month run-in period will be enrolled. A total of 76 subjects will be randomised to receive either transcranial magnetic stimulation or sham stimulation for 5 sessions within 2 weeks duration. Follow-up sessions will be conducted monthly for three consecutive months. Prior to treatment, subjects will be required to fill up questionnaires and undergo few procedures such as electroencephalography, transcranial Doppler ultrasound and biochemical analysis for serum serotonin, serum calcitonin gene-related peptide and serum beta-endorphin. These procedures will be repeated at month 3 after receiving the last treatment. The primary outcome measure of this study is the difference in mean monthly migraine days at baseline and at months 1, 2 and 3 after treatment sessions. DISCUSSION: Following evidence from previous studies showing restoration of dorsolateral prefrontal cortex (DLPFC) activation to almost normal level, the rTMS intervention will target left DLPFC in this study. An intermediate duration of treatment sessions is selected for this study. It is set to five treatment sessions given within 2 weeks duration. TRIAL REGISTRATION: ClinicalTrials.gov NCT03556722 . Registered on 14 June 2018.

Anti-Wolbachia therapy for onchocerciasis & lymphatic filariasis: Current perspectives.

Onchocerciasis and lymphatic filariasis (LF) are human filarial diseases belonging to the group of neglected tropical diseases, leading to permanent and long-term disability in infected individuals in the endemic countries such as Africa and India. Microfilaricidal drugs such as ivermectin and albendazole have been used as the standard therapy in filariasis, although their efficacy in eliminating the diseases is not fully established. Anti-Wolbachia therapy employs antibiotics and is a promising approach showing potent macrofilaricidal activity and also prevents embryogenesis. This has translated to clinical benefits resulting in successful eradication of microfilarial burden, thus averting the risk of adverse events from target species as well as those due to co-infection with loiasis. Doxycycline shows potential as an anti-Wolbachia treatment, leading to the death of adult parasitic worms. It is readily available, cheap and safe to use in adult non-pregnant patients. Besides doxycycline, several other potential antibiotics are also being investigated for the treatment of LF and onchocerciasis. This review aims to discuss and summarise recent developments in the use of anti-Wolbachia drugs to treat onchocerciasis and LF.

Acute disseminated encephalomyelitis in dengue viral infection.

Dengue is the most common arboviral disease affecting many countries worldwide. An RNA virus from the flaviviridae family, dengue has four antigenically distinct serotypes (DEN-1-DEN-4). Neurological involvement in dengue can be classified into dengue encephalopathy immune-mediated syndromes, encephalitis, neuromuscular or dengue muscle dysfunction and neuro-ophthalmic involvement. Acute disseminated encephalomyelitis (ADEM) is an immune mediated acute demyelinating disorder of the central nervous system following recent infection or vaccination. This monophasic illness is characterised by multifocal white matter involvement. Many dengue studies and case reports have linked ADEM with dengue virus infection but the association is still not clear. Therefore, this article is to review and discuss concerning ADEM in dengue as an immune-medicated neurological complication; and the management strategy required based on recent literature.

Managing post stroke hyperglycaemia: moderate glycaemic control is better? An update.

Post stroke hyperglycaemia (PSH) is prevalent in acute ischaemic stroke (AIS) patients and it has been associated with a dismal outcome of death and disability. Insulin has been proven to attenuate glucose effectively in stroke patients, thus many trials over the years had studied the efficacy of intensive treatment aiming at normalization of blood sugar level in order to improve the bleak outcomes of PSH. However, tight glycaemic control failed to be translated into clinical benefits and the outcomes are no different from the conventional approach, despite the costly healthcare expenditure invested. On the contrary, it brings more significant harm than the intended benefit, as 1 in every 9 treated patients had symptomatic hypoglycaemia. Thus, the benefits of tight glucose control, if any, are overshadowed by this potential risk of hypoglycaemia causing permanent neurological injury. Therefore, international practice guidelines recommend for less aggressive treatment to maintain blood glucose level within an appropriate range in AIS patients. However, there are limited details for stroke-specific glycaemic management and this made management of PSH particularly difficult. This review is to discuss and provide suggestions concerning glycaemic control in acute ischaemic stroke; the direction of its future prospective clinical trials and the treatment strategy required based on recent literature.