Dengue counts among the most commonly encountered arboviral diseases, representing the fastest spreading tropical illness in the world. It is prevalent in 128 countries, and each year >2.5 billion people are at risk of dengue virus infection worldwide. Neurological signs of dengue infection are increasingly reported. In this review, the main neurological complications of dengue virus infection, such as central nervous system (CNS), peripheral nervous system, and ophthalmic complications were discussed according to clinical features, treatment and possible pathogenesis. In addition, neurological complications in children were assessed due to their atypical clinical features. Finally, dengue infection and Japanese encephalitis were compared for pathogenesis and main clinical manifestations.

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Neurological Manifestations of Dengue Infection

Introduction: Uremic syndrome of chronic kidney disease (CKD) is a term used to describe clinical, metabolic, and hormonal abnormalities associated with progressive kidney failure. It is a rapidly growing public health problem worldwide. Nervous system complications occur in every patient with uremic syndrome of CKD. Areas covered: This review summarized central and peripheral nervous system complications of uremic syndrome of CKD and their pathogenic mechanisms. They include cognitive deterioration, encephalopathy, seizures, asterixis, myoclonus, restless leg syndrome, central pontine myelinolysis, stroke, extrapyramidal movement disorders, neuropathies, and myopathy. Their pathogenic mechanisms are complex and multiple. They include (1) accumulation of uremic toxins resulting in neurotoxicity, blood-brain barrier injury, neuroinflammation, oxidative stress, apoptosis, brain neurotransmitters imbalance, ischemic/microvascular changes, and brain metabolism dysfunction (e.g. dopamine deficiency), (2) metabolic derangement (as acidosis, hypocalcemia, hyperphosphatemia, hypomagnesemia, and hyperkalemia); (3) secondary hyperparathyroidism, (4) erythropoietin and iron deficiency anemia, (5) thiamin, vitamin D, and other nutritional deficiencies, (6) hyperhomocysteinemia, and (7) coagulation problems. Expert commentary: Nervous system complications of uremia contribute to the patients' morbidity and mortality. Optimizing renal replacement therapy, correction of associated metabolic and medical conditions, and improved understanding of possible pathogenic mechanisms of these complications is a major target for their prevention and treatment.

Neurologic conditions and disorders of uremic syndrome of chronic kidney disease: presentations, causes, and treatment strategies.

Early aetiological diagnosis is of paramount importance for childhood dystonia because some of the possible underlying conditions are treatable. Numerous genetic and non-genetic causes have been reported, and diagnostic workup is often challenging, time consuming and costly. Recently, a paradigm shift has occurred in molecular genetic diagnostics, with next-generation sequencing techniques now allowing us to analyse hundreds of genes simultaneously. To ensure that patients benefit from these new techniques, adaptation of current diagnostic strategies is needed. On the basis of a systematic literature review of dystonia with onset in childhood or adolescence, we propose a novel diagnostic strategy with the aim of helping clinicians determine which patients may benefit by applying these new genetic techniques and which patients first require other investigations. We also provide an up-to-date list of candidate genes for a dystonia gene panel, based on a detailed literature search up to 20 October 2014. While new genetic techniques are certainly not a panacea, possible advantages of our proposed strategy include earlier diagnosis and avoidance of unnecessary investigations. It will therefore shorten the time of uncertainty for patients and their families awaiting a definite diagnosis.

https://jnnp.bmj.com/content/jnnp/86/7/774.full.pdf

Dystonia in children and adolescents: a systematic review and a new diagnostic algorithm

A full-length genome infectious clone is a powerful tool for functional assays in virology. In this study, using a chemical synthesized complete genome of Japanese encephalitis virus (JEV) strain SA14 (GenBank accession no. U14163), we constructed a full-length genomic cDNA clone of JEV. The recovered virus from the cDNA clone replicated poorly in baby hamster kidney (BHK-21) cells and in suckling mice brain. Following serial passage in BHK-21 cells, adaptive mutations within the NS2B and NS4A proteins were recovered in the passaged viruses leading to viruses with a large-plaque phenotype. Mutagenesis analysis, using a genome-length RNA and a replicon of JEV, demonstrated that the adaptive mutations restored replication to different degrees, and the restoration efficiencies were in the order: NS2B-T102M<NS4A-R79K<NS2B-T102M+NS4A-R79K. An in vivo virulence assay in mice showed that the recombinant virus containing double mutations showed similar virulence to the WT SA14 (GenBank accession no. M55506). This study reports the first chemically synthesized JEV. A reverse genetics assay demonstrated that substitutions of NS2B-T102M and NS4A-R79K altered JEV replication.

Recovery of a chemically synthesized Japanese encephalitis virus reveals two critical adaptive mutations in NS2B and NS4A.

This article explores the broad spectrum of viral and prion central nervous system infections, highlights clinical and neuroimaging features of special interest, and serves as a complementary installment to an earlier article published in this journal on bacterial, fungal, and parasitic central nervous system infections.

Viral and Prion Infections of the Central Nervous System: Radiologic-Pathologic Correlation: From the Radiologic Pathology Archives.

Clinical and radiological spectrum of Japanese encephalitis.

Background: Acute hypokalemic paralysis, characterized by acute flaccid paralysis is primarily a calcium channelopathy, but secondary causes like renal tubular acidosis (RTA), thyrotoxic periodic paralysis (TPP), primary hyperaldosteronism, Gitelman's syndrome are also frequent. Objective: To study the etiology, varied presentations, and outcome after therapy of patients with hypokalemic paralysis. Materials And Methods: All patients who presented with acute flaccid paralysis with hypokalemia from October 2009 to September 2011 were included in the study. A detailed physical examination and laboratory tests including serum electrolytes, serum creatine phosphokinase (CPK), urine analysis, arterial blood gas analysis, thyroid hormones estimation, and electrocardiogram were carried out. Patients were further investigated for any secondary causes and treated with potassium supplementation. Result: The study included 56 patients aged 15-92 years (mean 36.76 ± 13.72), including 15 female patients. Twenty-four patients had hypokalemic paralysis due to secondary cause, which included 4 with distal RTA, 4 with Gitelman syndrome, 3 with TPP, 2 each with hypothyroidism, gastroenteritis, and Liddle's syndrome, 1 primary hyperaldosteronism, 3 with alcoholism, and 1 with dengue fever. Two female patients were antinuclear antibody-positive. Eleven patient had atypical presentation (neck muscle weakness in 4, bladder involvement in 3, 1 each with finger drop and foot drop, tetany in 1, and calf hypertrophy in 1), and 2 patient had respiratory paralysis. Five patients had positive family history of similar illness. All patients improved dramatically with potassium supplementation. Conclusion: A high percentage (42.9%) of secondary cause for hypokalemic paralysis warrants that the underlying cause must be adequately addressed to prevent the persistence or recurrence of paralysis.

Clinical and biochemical spectrum of hypokalemic paralysis in North: East India.

Background : Symptomatic neurosyphilis (NS) can have varied syndromic presentations: Meningitis, meningovascular and parenchymatous involvement. Aims : To evaluate the different types of clinical syndrome of NS in a tertiary care hospital. Material and Methods : This was a study of clinical profile of 16 patients with NS, seen in between August 2008 and December 2010. Results : There were 13 male and 3 female patients in the age group of 23-48 years. The clinical syndromes included: Neuropsychiatric syndromes (10), myelopathy (5), and posterior circulation stroke (1). Neuropsychiatric symptoms were dementia, behavioral abnormalities, chronic psychosis, and myelopathy syndromes included acute transverse myelitis (ATM), chronic myelopathy, and syphilitic amyotrophy. Thirteen patients had positive venereal disease research laboratory test (VDRL) and/or high Treponema pallidum hemagglutination titer in blood. Cerebrospinal fluid was positive for VDRL in 14 patients, raised protein was seen in 13 patients and lymphocytic pleocytosis was seen in 10 patients. Human immunodeficiency virus serology was negative in all the patients. Fourteen patients fulfilled the criteria of definitive NS and two of presumptive NS. All the patients except one received injection Procaine penicillin for 14 days. The patient with myelitis received a course of steroid, and one patient with associated hypothyroidism received thyroid supplement in addition to penicillin. On follow-up, dementia of short duration and ischemic stroke improved significantly and clinical status remained the same for ATM; others with mild symptoms improved with residual deficit. Conclusion : Syphilis can affect any part of the neuraxis. A high index of clinical suspicion is required to diagnose NS and institute the treatment early, particularly in patients with promiscuous sexual behavior.

Clinical spectrum of neurosyphilis in North East India

Introduction: Major categories of endocrine myopathy include those associated with: Adrenal dysfunction (as in Cushing's disease or steroid myopathy); thyroid dysfunction (as in myxedema coma or thyrotoxic myopathy); vitamin D deficiency; parathyroid dysfunction; and pituitary dysfunction. Steroid myopathy is the most common endocrine myopathy. Objective: To study the etiology, varied presentations, and outcome after therapy of patients with endocrine myopathies. Materials and Methods: Myopathy was evaluated by the standard clinical procedures: Detailed clinical history, manual muscle strength testing, and creatine phosphokinase (CPK). Endocrine disorders were diagnosed as per clinical features and biochemical parameters. The treatment was given to patients as per underlying endocrine disease. Myopathy was assessed before and after treatment. Results: Out of the 37 patients who were diagnosed with endocrine myopathies, thyroid dysfunction was the most common cause (17 cases), followed by vitamin D deficiency in nine, adrenal dysfunction in six, parathyroid dysfunction in three, and pituitary dysfunction in two. Some patients had atypical presentation (repeated falls in one, tongue fasciculations in one, neck weakness in five, one with ptosis and facial weakness, asymmetrical onset in one, and calf hypertrophy in one. The serum creatine kinase (CK) concentration did not correlate with muscle weakness. Following the treatment regimen which was specific for a given myopathy, 26 patients recovered fully. Conclusion: We found varied clinical presentations of endocrine myopathies. All the patients with neuromuscular complaints should be investigated for endocrine causes because significant number of them recovers fully with specific treatment.

Myopathies of endocrine disorders: A prospective clinical and biochemical study.

Central nervous system tuberculosis (TB) is the most severe extra pulmonary TB having a high mortality and morbidity. Objective To study the various clinical, biochemical, and radiological spectrum of intracranial TB. Materials and method Ninety-three patients were enrolled in this prospective study after ethical clearance and consent from August 2013 to May 2015. The entire clinical course with complications and predictors of mortality were assessed. Results 36 females (38.7%) and 57 males (61.3%) were included whose mean age of presentation was 32.3 ± 17.05 years. Alcohol was the most common risk factor seen in 19.4%. Headache (90.3%) was the most common symptom. Co-infection with human immunodeficiency virus, cryptococcal, and toxoplasmosis were seen in 11, 3, and 2 patients, respectively. Cerebrospinal fluid analysis showed acid-fast bacilli in 1 patient; polymerase chain reaction for TB and BACTEC was positive in one and three patients, respectively. Neuroimaging showed basal exudates (21.7%), tuberculoma (28.6%), brain edema (27%), hydrocephalus (32.9%), infarct (21%), and abscess (2.9%). Complications were noted such as brain edema (24.7%), vasculitis (26.9%), hydrocephalus (17.2%), hyponatremia (11.8%), drug-induced hepatitis (4.3%), and drug rash in 5 patients (5.4%). A total of 25 patients (26.9%) died and 38 patients (40.9%) developed neurological sequelae like hemiparesis, paraparesis, visual loss, and hearing loss. Logistic regression showed that a Glasgow scale of Conclusion Lack of sensitive diagnostic method and criteria makes central nervous system TB a challenge where early diagnosis and prompt management is required.

Ashok K Kayal

Papers

Clinical and radiological spectrum of Japanese encephalitis.

Clinical and biochemical spectrum of hypokalemic paralysis in North: East India.

Clinical spectrum of neurosyphilis in North East India

Myopathies of endocrine disorders: A prospective clinical and biochemical study.

Clinical and radiological spectrum of intracranial tuberculosis: A hospital based study in Northeast India