Analysis of Clinical and Metabolic Profile of Acute Neuromuscular Weakness Related to Hypokalemia.

OBJECTIVE: Acute neuromuscular weakness related to hypokalemia is a readily treatable disorder associated with diverse aetiologies. In this study we aim to report clinical pattern and biochemical features to identify the different aetiologies of the hypokalemic neuromuscular weakness. METHODS: Retrospective reviews of the medical record were analysed. Evaluation included demography, clinical features, investigations performed to ascertain the aetiologies. All the patients were categorised in to 3 groups; Idiopathic hypokalemic paralysis (IHP), dengue associated hypokalemic paralysis (DHP) and secondary group (SG) which included renal tubular acidosis (RTA- 1 and 2), thyrotoxic periodic paralysis (TPP) and Gitelman's syndrome (GS). RESULTS: Forty patients were analysed and the mean age was 31.78 (range, 14-60) years and 35 (87.5%) were male.The underlying aetiologies comprised of IHP in 20, DHP in 12, RTA-2 in 4, RTA-1 in 2, TPP, GS in one each. Weakness on Medical Research Council (MRC) grade was 2.6±1.19 (range 0-4). Comparison of various clinical and laboratory parameters revealed that more patient in IHP and SG had recurrent attack (p=0.001). DHP group had low platelet (p=0.001), high creatine phosphokinase (CPK) (p=0.01) and serum glutamic oxaloacetic transaminase (SGOT) (p=0.008). SG had significantly lower serum potassium (p=0.04) and more time to improve (p=0.02). Recovery time correlated negatively with serum potassium (r=-0.44, p=0.004) and grade of weakness (r= 0.42,p=0.007). CONCLUSION: In half of the patients, secondary causes were identified. After IHP, the DHP emerged as second common cause in post monsoon season. SG had significantly lower serum potassium, recurrent attack and more time to improve.

Chronic Migraine Responding to Intravenous Thiamine: A Report of Two Cases.

BACKGROUND: Migraine is a risk factor for thiamine deficiency and Wernicke's encephalopathy (WE). WE is a highly underdiagnosed condition. The misdiagnosis is associated more with early or mild WE. The interrelation between migraine and thiamine deficiency is unknown CASE REPORTS: Here, we report two female patients with chronic migraine. During examinations, we also noted clinical signs pertinent with a diagnosis of WE. Both patients had low blood thiamine level. Intravenous thiamine supplementation led to the improvement of both WE and associated headaches. DISCUSSION: Nausea, vomiting, and anorexia of migraine may lead to mild to moderate thiamine deficiency and WE. Review of the literature suggests that WE in early or subclinical form will have nonspecific symptoms that may include frequent headache, nausea, vomiting, and anorexia. So, WE in the early stage may simulate migrainous features and this will further aggravate thiamine deficiency and a vicious cycle may be formed, and that will progressively increase the chronicity of headaches and other features. Breaking of this cycle by thiamine supplementation might be a promising therapy in a subset of patients with chronic migraine. CONCLUSION: Thiamine deficiency due to nausea, vomiting and anorexia of migraine may further aggravate migraine like headaches in cyclical pattern.

(68)Ga based probe for Alzheimer's disease: synthesis and preclinical evaluation of homodimeric chalcone in ß-amyloid imaging.

In an attempt to explore use of PET radioisotope, (68)Ga, in the diagnosis of Alzheimer's disease, a metal-based homodimeric ligand exhibiting high affinity towards Aß aggregates was designed by conjugating two chalcone units with the chelating system, diethylenetriaminepentaacetic acid. Bischalcone derivative, 5,8-bis(carboxymethyl)-13-(4-((E)-3-(4-(dimethylamino)phenyl)acryloyl)phenoxy)-2-(2-(2-(4-((E)-3-(4-(dimethylamino)phenyl)acryloyl)phenoxy)ethylamino)-2-oxoethyl)-10-oxo-2,5,8,11-tetraazatridecane-1-carboxylic acid, DT(Ch)2 was synthesized in 95% yield with high purity. It was radiolabelled with (68)Ga under mild conditions with 85.4% efficiency and 9.5-10 MBq nmol(-1) specific activity. An in vitro binding assay on Aß42 aggregates displayed high binding affinity of (68)Ga-DT(Ch)2 and inhibition constant of 4.18 ± 0.62 nM. The fluorescent properties of the ligand with peaks of absorption/emission at 410/540 nm exhibited a blue shift with 5.5-fold increase in emission intensity on binding with Aß aggregates. Blood kinetics of the complex performed on normal rabbit exhibited fast clearance (t1/2(F) = 24 ± 0.08 min; t1/2(S) = 2 h 40 ± 0.04 min). Ex vivo biodistribution analysis demonstrated blood-brain barrier penetration with brain uptake of 1.24 ± 0.31% ID g(-1) at 2 min p.i. and rapid washout with negligible activity (0.36% ID g(-1)) left at 30 min p.i. These preliminary studies reveal that the bivalent approach of synthesis had minimal effect on binding affinity, signifying that the developed (68)Ga-complex, (68)Ga-DT(Ch)2, may offer a new perspective in generator produced PET imaging probes for Alzheimer's disease.