Neuropsychiatric disorders (NPDs) are a huge burden to the patient, their family, and society. NPDs have been greatly associated with cardio-metabolic comorbidities such as obesity, type-2 diabetes mellitus, dysglycaemia, insulin resistance, dyslipidemia, atherosclerosis, and other cardiovascular disorders. Antipsychotics, which are frontline drugs in the treatment of schizophrenia and off-label use in other NPDs, also add to this burden by causing severe metabolic perturbations. Despite decades of research, the mechanism deciphering the link between neuropsychiatric and metabolic disorders is still unclear. In recent years, transient receptor potential Ankyrin 1 (TRPA1) channel has emerged as a potential therapeutic target for modulators. TRPA1 agonists/antagonists have shown efficacy in both neuropsychiatric disorders and appetite regulation and thus provide a crucial link between both. TRPA1 channels are activated by compounds such as cinnamaldehyde, allyl isothiocyanate, allicin and methyl syringate, which are present naturally in food items such as cinnamon, wasabi, mustard, garlic, etc. As these are present in many daily food items, it could also improve patient compliance and reduce the patients' monetary burden. In this review, we have tried to present evidence of the possible involvement of TRPA1 channels in neuropsychiatric and metabolic disorders and a possible hint towards using TRPA1 modulators to target appetite, lipid metabolism, glucose and insulin homeostasis and inflammation associated with NPDs.
Parkinsonism as a neurologic manifestation of dengue infection is rare with only 1 reported case in an adult patient. We report a case of a 6-year-old child with self-limiting post-dengue encephalopathy and Parkinsonism. This is the first reported pediatric case of post-dengue Parkinsonism and expands the neurologic manifestations associated with dengue infection in children. Clinicians should consider the possibility of post-dengue Parkinsonism in children with a history of pyrexia from endemic areas of dengue.
Dengue virus is a flavivirus transmitted by the mosquitoes, Aedes aegypti and Aedes albopictus. Dengue infection by all four serotypes (DEN 1 to 4) is endemic globally in regions with tropical and subtropical climates, with an estimated 100-400 million infections annually. Among those hospitalized, the mortality is about 1%. Neurological involvement has been reported to be about 5%. The spectrum of neurological manifestations spans both the peripheral and central nervous systems. These manifestations could possibly be categorized into those directly related to dengue infection, i.e. acute and chronic encephalitis, indirect complications leading to dengue encephalopathy, and post-infectious syndrome due to immune-mediated reactions, and manifestations with uncertain mechanisms, such as acute transverse myelitis, acute cerebellitis and myositis. The rising trend in global dengue incidence calls for attention to a more explicit definition of each neurological manifestation for more accurate epidemiological data. The actual global burden of dengue infection with neurological manifestation is essential for future planning and execution of strategies, especially in the development of effective antivirals and vaccines against the dengue virus. In this article, we discuss the recent findings of different spectrums of neurological manifestations in dengue infection and provide an update on antiviral and vaccine development and their challenges.
The present study examines the gross anatomical features of anomalous lunate sulcus detected incidentally in a cadaveric brain and discusses its clinical importance. The absence of lunate sulcus was carefully studied in a dissected brain specimen. The absence of lunate sulcus was observed unilaterally on the right side of a cadaveric brain specimen. The lunate sulcus was clearly appreciated on the left side whilst on the right side it was absent. The right hemisphere of the cerebellum was also bigger in size as compared to the left. The absence of lunate sulcus is a rare finding, which may be detected incidentally. The anatomical knowledge of the lunate sulcus may be important for neurosurgeons operating on the occipital lobe and the radiologists interpreting CT scan.
A series of 18 cases of tuberculous encephalopathy (TBE) in children studied between June 1983 and October 1984 at Queen Elizabeth Hospital, Kota Kinabalu is presented. The data suggest that: the incidence is not as rare as previously thought; the occurrence of TBE is related to the absence of BCG vaccination; the presentation is often late; laboratory data, although helpful is not often confirmatory; early treatment is the key to better outcome; the clinical picture should outweigh laboratory diagnosis in the initial assessment and management.
This case series compared clinical variables and various combinations of immunotherapy received with outcomes of patients with severe acute necrotizing encephalopathy (ANE). We performed a retrospective review of clinical variables, immunotherapy received, and outcomes (based on the modified Rankin Scale) in Malaysia between February 2019 and January 2020. Twenty-seven children (12 male), aged 7 months to 14 years (mean 4 years) at diagnosis were included. Of these, 23 had an ANE severity score of 5 to 9 out of 9 (high risk). Eleven patients received tocilizumab (four in combination with methylprednisolone [MTP], seven with MTP + intravenous immunoglobulin [IVIG]) and 16 did not (two received MTP alone, 14 received MTP + IVIG). Nine died. Among the survivors, six had good outcomes (modified Rankin Score 0-2) at 6 months follow-up. All patients who received tocilizumab in combination with MTP + IVIG survived. Twenty children received first immunotherapy within 48 hours of admission. No significant association was found between the timing of first immunotherapy with outcomes. Those with brainstem dysfunction (p = 0.016) were observed to have poorer outcomes. This study showed a trend towards better survival when those with severe ANE were treated with tocilizumab in combination with MTP + IVIG. However, larger studies will be needed to determine the effect of this regime on the long-term outcomes.
A patient with a solitary intracranial cryptococcoma of the occipital lobe of the brain and a concomitant granuloma of similar aetiology in the breast is reported. Despite resistance of the causative fungus to 5-fluorocytosine in vitro, the patient responded well to radical excisional surgery and therapy with 5-fluorocytosine.
Cryptococcal infection of the brain as encountered in a tropical country is reviewed. The meningitic form is not uncommon and there has been, in the last decade, an apparent, if not real, rise in incidence in Malaysia as in Singapore. Only exceptionally was there overt evidence of immunological deficiency. Hydrocephalus was present in about three-quarters of the patients with meningitis and shunts were employed readily. The presence of multiple small intracerebral cysts could be suspected clinically but treatment for this complication was ineffective. The antifungal agent used most frequently was 5-fluorocytosine. Resistance to this drug developed in about one patient in four. There is a need for further epidemiological studies and for a continuing search for new antifungal agents.
Brain disorders remain the world's leading cause of disability, and account for more hospitalizations and prolonged care than almost all other diseases combined. The majority of drugs, proteins and peptides do not readily permeate into brain due to the presence of the blood-brain barrier (BBB), thus impeding treatment of these conditions.
Metabolic epilepsy is a metabolic abnormality which is associated with an increased risk of epilepsy development in affected individuals. Commonly used antiepileptic drugs are typically ineffective against metabolic epilepsy as they do not address its root cause. Presently, there is no review available which summarizes all the treatment options for metabolic epilepsy. Thus, we systematically reviewed literature which reported on the treatment, therapy and management of metabolic epilepsy from four databases, namely PubMed, Springer, Scopus and ScienceDirect. After applying our inclusion and exclusion criteria as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we reviewed a total of 43 articles. Based on the reviewed articles, we summarized the methods used for the treatment, therapy and management of metabolic epilepsy. These methods were tailored to address the root causes of the metabolic disturbances rather than targeting the epilepsy phenotype alone. Diet modification and dietary supplementation, alone or in combination with antiepileptic drugs, are used in tackling the different types of metabolic epilepsy. Identification, treatment, therapy and management of the underlying metabolic derangements can improve behavior, cognitive function and reduce seizure frequency and/or severity in patients.
A Danish woman aged 28 years who had travelled in the Far East developed cerebral symptoms with headache and visual disturbances. Migraine was suspected. Subsequent CT scanning revealed multiple processes and metastases were suspected. As the patient had travelled in the Far East 1 1/2 years previously, she was examined for neurocysticercosis. This diagnosis was established and the patient was successfully treated with praziquantel. On account of increased travelling activity, the possibility of neurocysticercosis should be borne in mind when dealing with patients with cerebral symptoms and relevant travelling histories.
We report a case of rhinocerebral mucormycosis in a 31 year old immunocompetent female presenting initially like acute rhinosinusitis with nasal stuffiness, severe headache, vomiting who soon developed isolated right lateral rectus palsy. Computed tomography (CT) scan of the Post-Nasal Spaces(PNS) showed an ill defined expansile heterogenous density mass in the sphenoid with extension into the ethmoids, nasal cavity, optic canal, superior orbital fissure, clivus and right temporal lobe with signal void in Magnetic Resonance Imaging (MRI). The debris and polypoid mucosa obtained on nasal endoscopy revealed mucormycosis on histopathologic examination. The patient was managed with urgent surgical debridement and medical management.