At Prabhakar

Delayed-onset encephalopathy and coma in acute organophosphate poisoning in humans

The objective of the study was to describe the clinical characteristics and course of delayed-onset organophosphate (OP) poisoning. In our clinical experience, we have noticed patients with onset of deep coma 4-7 days after hospital admission, clinical features that have not been previously described. We set up a prospective observational study over 1 year to formally characterize this observation. Thirty-five patients admitted to the intensive care unit (ICU) with severe OP poisoning and treated with atropine and supportive therapy were followed up. Oximes were not administered. Three patients developed delayed-onset coma after presenting with normal or near normal Glasgow coma score (GCS). They developed altered conscious state rapidly progressing to deep coma, 5.0+/-1.0 (mean+/-S.D.) days after OP ingestion. The GCS persisted at 2T for 4.3+/-2.1 days despite the cessation of sedative drugs at the onset of coma. During this period, the patients had miosed non-reacting pupils and no clinically detectable cortical or brainstem activity. Computed tomography of the brain and cerebrospinal fluid analysis were normal. Electroencephalogram showed bihemispheric slow wave disturbances. Two patients required atropine during this period to maintain heart rate and reduce secretions. In all three patients, no metabolic, infective or non-infective cause of altered conscious state was identified. With supportive therapy the GCS improved to 10T in 8.0+/-2.0 days. All patients survived to hospital discharge. Three other patients who developed a reduction in GCS (3T-7T) by 4.7+/-1.2 days but not progressing to coma and recovering (GCS 10T) in 3.3+/-0.6 days may have manifested delayed-onset encephalopathy. Delayed-onset coma appears to have a distinct clinical profile and course with complete resolution of symptoms with supportive therapy. Although persistent cholinesterase inhibition is likely to have contributed to the manifestations, the mechanism of coma and encephalopathy need to be explored in further trials. The good outcomes in these patients suggest that therapy should not be limited in OP-poisoned patients developing profound coma or encephalopathy during hospitalization.

In-laws, insecticide—and a mimic of brain death

In December, 2006, a 28-year-old woman from Andhra Pradesh, India, impulsively swallowed 50 mL of phorate (a diethyl organophosphorus insecticide) after quarrelling with her husband’s family, with whom she lived. Her inlaws saw her vomit and briefl y lose consciousness—and, suspecting what she had done, took her by moped to a local hospital. The patient was given gastric lavage, before being transferred by ambulance to the emergency department at our hospital, 400 km away. The patient arrived 9 h 30 min after her suicide attempt. Her giddiness and vomiting had persisted, and she now also had abdominal pain; but she was stable. 5 h after arrival, the patient became increasingly breathless; her arterial oxygen saturation decreased to 77%, necessitating intubation and ventilation. She was transferred to our intensive-care unit. We prescribed atropine, at 4 mg/h, to counteract the eff ects of organophosphate. Although the chest radiograph was clear, we suspected that the breathlessness was caused by aspiration, and prescribed penicillin and levofl oxacin. We also prescribed morphine and lorazepam, to keep the patient comfortable but easily arousable. We titrated the dose of atropine to the patient’s heart rate, but aimed also for quiet bowel sounds, pupils that were neither contracted nor dilated, a clear-sounding chest, and a systolic blood pressure higher than 90 mm Hg. The patient recovered steadily until her 4th day in hospital, when her score on the Glasgow coma scale (GCS) decreased to 8T (fi gure), prompting us to discontinue sedation. Over the next 12 h, the patient’s limbs trembled and jerked, although she did not have seizures; we noted that the muscular tone of the limbs had increased. The GCS score then decreased to 2T over the next 12–24 h. We could not fi nd any cause for the coma, other than organophosphate poisoning, despite doing blood tests (including arterial blood gases), CT of the head, a lumbar puncture, and monitoring the patient’s arterial oxygen saturations. The serum concentration of pseudocholinesterase was 254 IU/mL (normal range 3000– 6000 IU/mL). During the coma, fi ndings on examination were largely consistent with brain death: oculocephalic, pupillary, corneal, and deep-tendon refl exes were absent; the patient did not react to painful stimuli or caloric stimulation; she did not breathe spontaneously. Unlike in brain death, however, the pupils remained constricted. An electroencephalogram showed global suppression of cortical activity. We continued to prescribe atropine. After 5 days of deep coma, the patient started to recover, and was fully conscious by day 15. She later developed pneumonia, but was discharged from the hospital, in good health, after a 39-day stay. When last seen, in March, 2007, she was well. Organophosphates inhibit acetylcholin esterase, causing overstimulation of nicotinic, muscar inic, and central acetylcholine receptors. Neurological manifestations of organophosphate poisoning range from anxiety, restlessness, and tremors to seizures, central respiratory depression, and coma. Although neurological manifestations are usually observed shortly after poisoning occurs, they can be delayed. Recognition of delayed symptoms and signs can avert unfortunate misdiagnoses, such as brain death. Phorate is lipidsoluble: we conclude that much of the swallowed insecticide was absorbed by the patient’s body fat, and released several days into her hospital stay. Patients who have swallowed lipid-soluble organophosphates may benefi t from treatment with oximes, which separate organophosphate from acetylcholinesterase, for longer than patients who have swallowed other organophosphates. By contrast, gastric lavage may not be helpful, although patients’ relatives may demand it, as a sign that all possible eff orts are being made. Most hospitals in rural India are able to provide gastric lavage and atropine—however, few are able to intubate and ventilate the patient, and many prefer to avoid the legal and administrative complications of suicide attempts. Banning the most toxic pesticides in China and India could save more than 150 000 lives a year.

Mechanical thrombectomy for acute ischemic stroke in pregnancy using the penumbra system

Even though intravenous thrombolysis with tissue plasminogen activator (IV tPA) is the standard of care in acute ischemic stroke, its use in pregnancy is not clearly defined. Mechanical thrombectomy devices can be an option; however, literature on the use of such mechanical devices in stroke in pregnancy is lacking. Here we describe two cases that developed acute embolic stroke during pregnancy who were successfully treated by mechanical clot retrieval using the Penumbra system 28 (Penumbra Inc., Alameda, California, USA). To the best of our knowledge, these are the only case reports on the use of the Penumbra device in pregnant patients with acute ischemic stroke.

Human poisoning with hexastar™: A hexaconazole-containing agrochemical fungicide

We report a patient who ingested 500 ml of Hexastar 5.5% EC™, a hexaconazole-containing product. Clinical toxicity consisted primarily of central nervous system depression and generalized trembling. The patient recovered without sequelae with supportive therapy.

Stuck with a drowsy patient, evoke the Percheron

BACKGROUND Strokes caused by normal variants of the cerebral circulation can be difficult to diagnose, hence a high index of suspicion is needed. This case series discusses the clinical and radiological aspects of one such stroke caused by occlusion of the artery of Percheron (AOP). MATERIALS AND METHODS Computerized discharge summaries, outpatient records and imaging from picture archiving and communication system (PACS, GE), of patients with AOP infarction over a period of 12-years (2002-2014) were identified and their clinical and radiological features analyzed. RESULTS Of 3589 strokes (both ischemic and hemorrhagic), 17 (0.47%) were due to AOP infarction. Their mean age was 50 years (range: 31-72 years). Disorders of consciousness (94%) were the most common presenting symptoms followed by gaze (53%) and memory impairment (24%). At follow-up, 2/17 (12%) patients developed extrapyramidal features. All patients had bilateral paramedian thalamic infarcts on magnetic resonance imaging (MRI). Associated anterior thalamic (5/17; 30%) and mid brain (10/17; 59%) infarcts were also seen. CT scan done in 11/17 patients prior to the MRI picked up only 6/11 (55%) of these infarcts. The most common etiological factors detected using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria were cardio embolic (8/17; 47%) followed by small vessel occlusion (7/17; 41%). Mortality occurred in 2/17 (12%) patients. At 6 months, a modified Rankin score of 2 or less was seen in 8/17 (47%) patients. CONCLUSIONS Artery of Percheron infarcts should be considered in the differential diagnosis of patients presenting with sudden alterations in consciousness. MRI should be the investigation of choice. An embolic etiology should be actively looked for.

Study of refractory status epilepticus from a tertiary care center

Objectives: To determine the proportion of refractory status epilepticus (RSE) and super-RSE (SRSE) among patients with status epilepticus (SE) and to analyze RSE and non-RSE (NRSE) in terms of etiology and predictors for RSE. Materials and Methods: Patients were identified from discharge summaries database with keywords of SE and records of the portable electroencephalogram (EEG) machine from January 2011 to March 2016. Results: Two hundred and eighteen events were included in the study with 114 (52.3%) males, bimodal age preponderance age <5 years 30%, and second peak in age 15–65 years 52.8%, preexisting seizures were present in 34.4% (n = 75). Nearly 77.1% had NRSE (n = 168) and 22.9% had RSE (n = 50). This included 17 patients with SRSE (n = 17, 7.8% of all SE). Central nervous system (CNS) infection was a single largest etiological group in SE (69/218, 31.7%). In RSE, autoimmune encephalitis (17/50) and CNS infection (13/50) were the largest groups. De novo seizures (P = 0.007), low sensorium at admission (P = 0.001), low albumin at admission (P = 0.002), and first EEG being abnormal (P = 0.001) were risk factors on bivariate analysis. An unfavorable status epilepticus severity score (STESS) was predictive for RSE (P = 0.001). On multivariate analysis, de novo seizures (P = 0.009) and abnormal EEG at admission (P = 0.03) were predictive for RSE. Conclusions: Fifty patients had RSE (22.9%), of which 17 went on to become SRSE (7.8%). Unfavorable STESS score was predictive for RSE on bivariate analysis. On multivariate analysis, de novo seizures and abnormal initial EEG were predictors of RSE.

An unusual case of inflammatory necrotizing myopathy and neuropathy with pipestem capillaries

Necrotizing myopathy with pipestem capillaries is a form of chronic inflammatory myopathy, with histopathology showing necrotizing myopathy, minimal cellular infiltration, and microangiopathy. A 30-year-old female presented with progressive limb weakness of 6 months, with skin pigmentation and Raynauds phenomenon. Serum creatine phosphokinase was 3990 u/L. Muscle biopsy showed necrotic fibers, focal sparse perivascular inflammation/perifascicular atrophy, endomysial/epimysial vessel wall thickening with luminal narrowing. The features were of inflammatory necrotizing myopathy and neuropathy with pipestem capillaries/microangiopathy. She was pulsed with intravenous immunoglobulin, methylprednisolone, and cyclophosphamide and showed a good improvement. In the absence of widespread inflammatory response and classical histopathology findings, it is important to diagnose this condition as it shows a good response to aggressive and prolonged immunotherapy.

Sonothrombolysis for acute ischemic stroke - Break on through to the other side.

Background: Intravenous (IV) tissue plasminogen activator (tPA) infusion combined with transcranial low-frequency ultrasound waves targeted on the occluded arterial segment (sonothrombolysis) can increase recanalization in large artery-acute ischemic stroke (LA-AIS). Aims: To evaluate the benefits of sonothrombolysis in LA-AIS. Settings and Designs: An open-labeled observational study done in a quaternary care teaching hospital. Methodology: Patients with LA-AIS within the window period (<4.5 h) with no contraindications for IV-recombinant tPA were sonothrombolysed. Recanalization was monitored and graded using the transcranial Doppler thrombolysis in brain ischemia (TIBI) flow criteria and also by time of flight magnetic resonance angiography using a modified thrombolysis in myocardial infarction score. Parenchymal changes were assessed using computed tomography (CT) or diffusion-weighted imaging-Alberta Stroke Programme Early CT Score. National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were used to assess the outcome. Results: Eighteen patients underwent sonothrombolysis and the mean onset to needle time was 138 min (range 65–256). TIBI residual flow grade of ≥2 was seen in 15 of 18 patients (83%). Immediate dramatic improvement (NIHSS score ≤3 points or improvement by ≥10 points) was seen in 6 of 18 patients (30%) and in 9 of 18 patients (50%) within the next 24 h. Two patients (one with TIBI 0, another with re-occlusion) underwent mechanical thrombectomy post-sonothrombolysis. Symptomatic hemorrhage occurred in 5.5% of the patients. At 6 months, 2 of 18 patients (11%) died and 10 of 16 patients (63%) achieved mRS ≤2. Conclusions: Sonothrombolysis appears to be a safe way to augment the effect of tPA without increasing the door to needle time with the added advantage of observing flow through the occluded artery in real time.

Determination of serum carbamazepine concentration using dried blood spot specimens for resource-limited settings

ABSTRACT Objectives: Carbamazepine (CBZ) is a commonly used anti-epileptic in rural hospitals in India. These hospitals lack the facilities to measure CBZ concentration; however, in larger hospitals this is performed using high performance liquid chromatography (HPLC). Dried blood spot (DBS) represents a feasible matrix for safe transportation by post/courier. This study was to determine whether the concentration of CBZ in serum can be predicted from that measured in DBS using an inexpensive HPLC method and inexpensive standard filter paper. Methods: CBZ in serum and DBS from 80 epileptic patients were measured using a validated HPLC assay. The data was then randomly divided into two groups; simple Deming regression was performed with the first group and validation was performed using the second. Results: There was a good correlation between the serum and DBS concentrations (r = 0.932) in the first group. The regression equation obtained was: predicted serum concentration = DBS concentration x 0.83 + 1.09. In the validation group, the correlation between the predicted and actual serum concentrations was also good (r = 0.958), and the mean difference between them was only 0.28 μg/ml (p = 0.8062). The imprecision and bias in both the groups were acceptable. Conclusion: Using inexpensive materials, serum CBZ concentrations can be accurately predicted from DBS specimens. This method can be recommended for the therapeutic drug monitoring of CBZ in resource-limited settings.

Clinical spectrum, therapeutic outcomes, and prognostic predictors in sjogren's syndrome-associated neuropathy

Objectives: There are limited data regarding long-term follow-up and therapeutic outcomes in Sjogrens syndrome (SS)-associated peripheral neuropathy. In this study, we aim to study the clinical, electrophysiological spectrum and therapeutic responses among the different subtypes of SS-associated neuropathy. The predictors of suboptimal treatment response will be identified. Methods: The study included a retrospective cohort of patients with SS-associated neuropathy between January 2012 and November 2015. Baseline clinical, laboratory, electrophysiological data and details of treatment were noted. Therapeutic outcomes were assessed at follow-up and compared among the different subtypes. Prognostic predictors were determined using logistic regression analysis. Results: Fifty-four patients were included in the study. Sensory ataxic neuropathy (17, including 9 with sensory ganglionopathy) and radiculoneuropathy (11) were the main subtypes. Notable atypical presentations included acute neuropathies, pure motor neuropathies, and hypertrophic neuropathy. Concomitant autoimmune disorders were present in 24 (44.4%) patients. Most presentations were subacute-chronic (51, 94.4%). Minor salivary gland biopsy had a higher yield compared to serological markers (81.5 vs. 44.4%). Sensory ataxic neuropathy was associated with greater severity and autonomic dysfunction. Improvement was noted in 33 (61%) patients. Cranial neuropathy and radiculoneuropathy subtypes were associated with the best treatment responses. Chronicity, orthostatic hypotension, baseline severity, and marked axonopathy (nerve biopsy) were predictive of a suboptimal therapeutic response. Conclusions: The study highlights the heterogeneous spectrum, atypical presentations, and differential therapeutic responses. SS-associated neuropathy remains underdiagnosed. Early diagnosis and prompt initiation of immunotherapy before worsening axonal degeneration is paramount. SS-associated neuropathy need not necessarily be associated with a poor prognosis.