Samuel George Hansdak

Acute undifferentiated febrile illness in patients presenting to a Tertiary Care Hospital in South India: clinical spectrum and outcome

Background: Acute undifferentiated febrile illness (AUFI) may have similar clinical presentation, and the etiology is varied and region specific. Materials and Methods: This prospective observational study was conducted in a tertiary hospital in South India. All adult patients presenting with AUFI of 3-14 days duration were evaluated for etiology, and the differences in presentation and outcome were analyzed. Results: The study cohort included 1258 patients. A microbiological cause was identified in 82.5% of our patients. Scrub typhus was the most common cause of AUFI (35.9%) followed by dengue (30.6%), malaria (10.4%), enteric fever (3.7%), and leptospirosis (0.6%). Both scrub typhus and dengue fever peaked during the monsoon season and the cooler months, whereas no seasonality was observed with enteric fever and malaria. The mean time to presentation was longer in enteric fever (9.9 [4.7] days) and scrub typhus (8.2 [3.2] days). Bleeding manifestations were seen in 7.7% of patients, mostly associated with dengue (14%), scrub typhus (4.2%), and malaria (4.6%). The requirement of supplemental oxygen, invasive ventilation, and inotropes was higher in scrub typhus, leptospirosis, and malaria. The overall mortality rate was 3.3% and was highest with scrub typhus (4.6%) followed by dengue fever (2.3%). Significant clinical predictors of scrub typhus were breathlessness (odds ratio [OR]: 4.96; 95% confidence interval [CI]: 3.38-7.3), total whole blood cell count >10,000 cells/mm 3 (OR: 2.31; 95% CI: 1.64-3.24), serum albumin <3.5 g % (OR: 2.32; 95% CI: 1.68-3.2). Overt bleeding manifestations (OR: 2.98; 95% CI: 1.84-4.84), and a platelet count of <150,000 cells/mm 3 (OR: 2.09; 95% CI: 1.47-2.98) were independent predictors of dengue fever. Conclusion: The similarity in clinical presentation and diversity of etiological agents demonstrates the complexity of diagnosis and treatment of AUFI in South India. The etiological profile will be of use in the development of rational guidelines for control and treatment of AUFI.

Cerebrovascular injury in cryptococcal meningitis

Background Cryptococcal meningitis continues to be one of the common causes of chronic central nervous system infection worldwide. Individuals with cryptococcal meningitis can occasionally present with small vessel vasculitis causing infarcts primarily in the basal ganglia, internal capsule, and thalamus. Literature regarding patterns of cerebrovascular injury among patients with cryptococcal meningitis is scanty, and outcome following these vascular involvements is unknown. Aim To study the clinical profile, imaging findings, and details of vascular territory involved among patients admitted with cryptococcal meningitis and central nervous system infarct in a tertiary care center from India. And to compare the outcomes of patients of cryptococcal meningitis with or without central nervous system infarcts in terms of mortality and morbidity, Methodology A total of 151 patients with microbiologically proven cryptococcal meningitis over a time span of 11 years were retrospectively enrolled into the study. Of these, 66 patients met the inclusion criteria of having appropriate imaging of the brain. The presence of infarct in the imaging was analyzed by two independent radiologists. Patterns of central nervous system involvement and types of vascular injury were ascertained based on radiological parameters. Clinical parameters and outcomes of patients with and without infarcts were compared. Results Twenty (13%) of these patients had evidence of central nervous system infarcts on imaging. The mean age of patients with and without infarcts was 41 years and 38 years, respectively. Male predominance was present among both the groups. The presence of fever, neck stiffness, positive blood culture, and hydrocephalus in central nervous system imaging was similar among patients with or without infarct. Longer duration of illness, low sensorium at the time of presentation, low Glasgow Coma Scale score, presence of meningeal inflammation, cryptococcomas, and basal exudates in imaging were higher in patients with infarct. All the infarcts were of the lacunar type. Sixty percent of the cerebrovascular infarcts were acute in nature, 50% of these being multiple. Unilateral infarcts were seen in 70% of the patients. The most common site of infarct was the basal ganglia, others being distributed over the thalamus, frontal, temporal, parieto-occipital regions in the descending order. The presence of neurovascular involvement in the form of infarcts to the risk of morbidity and mortality had an odds ratio of 9.1 and 2.6, respectively. Conclusion Neurovascular involvement in chronic cryptococcal meningitis is a rare entity. These tend to present as multiple lacunar infarcts. Mortality and morbidity associated with these patients is higher when compared to patients who do not have infarcts. This result suggests that vascular injury plays a role in predicting outcome of patients with cryptococcal meningitis. Future studies are needed to understand the mechanism by which vascular events (infarcts) occur and result in poor outcome.

Dengue fever complicated by hemophagocytosis

Dengue is a common acute viral febrile illness in the tropics. Although the usual presentation is that of a self-limiting illness, its complications are protean. We report a 29-year-old man who presented with an acute febrile illness and was diagnosed with dengue hemorrhagic fever. Despite appropriate supportive therapy, the patient initially improved, but subsequently had clinical deterioration. Evaluation revealed features of hemophagocytic lymphohistiocytosis. He was successfully treated with glucocorticoids and had an uneventful recovery. This case adds to the limited adult cases of virus-associated hemophagocytic syndrome in the literature and the need for prompt recognition and treatment of this rare complication.

Extrapyramidal effects of acute organophosphate poisoning.

Abstract Background: There is limited information on extrapyramidal symptoms in acute organophosphate (OP) poisoning. We describe the course and outcome of severely poisoned patients who develop extrapyramidal manifestations. Methods: In this prospective observational study, spanning 8 months (Apr–Nov 2013) adult patients (>18 years) admitted with OP poisoning were enrolled. Patients on anti-psychotic therapy, those refusing consent or presenting with co-ingestions were excluded. Treatment included atropine and supportive care (e.g. ventilation and inotropes as indicated); oximes were not administered. The presence of rigidity, tremors, dystonia and chorea were assessed daily till discharge using modifications of the Unified Parkinson’s Disease rating scale and the Tremor rating scale. The presence of extrapyramidal manifestations was correlated with length of ventilation and hospital stay and mortality. Results: Of the 77 patients admitted with OP poisoning, 32 were enrolled; 17 (53.1%) developed extrapyramidal manifestations which included rigidity (94.1%), tremors (58.8%) and dystonia (58.8%). None developed chorea. The median (inter-quartile range) time of symptom onset was 8 (5–11) days; extrapyramidal features resolved in 11 (6–17) days. The median duration of intensive care stay in patients not developing extrapyramidal symptoms was 6 (2–8) days, indicating that most of these patients had recovered even before symptom onset in patients who developed extrapyramidal manifestations. Overall, 27/32 (84%) were ventilated. Hospital mortality was 6.25% (2/32). When compared with patients not developing extrapyramidal signs, those with extrapyramidal manifestations had significantly prolonged ventilation (5 versus 16 median days; p = 0.001) and hospitalization (8 versus 21 days; p < 0.001), reduced ventilator-free days (23 versus 12 days; p = 0.023) and increased infections (p = 0.03). The need for ventilation and mortality were not significantly different (p > 0.6). Extrapyramidal symptoms were not observed in non-OP poisoned patients with prolonged ICU stay. Conclusion: In this small series of acute OP poisoning, extrapyramidal manifestations were common after 1 week of intensive care but self-limiting. They are significantly associated with longer duration of ventilation and hospital stay.

Is Ross Syndrome an Autoimmune Entity? A Case Series of 11 Patients

BACKGROUND Ross syndrome is diagnosed by the presence of segmental anhidrosis, areflexia, and tonic pupils. Fewer than 60 cases have been described in literature so far. There have been reports of presence of antibodies in such patients, suggesting an autoimmune pathogenesis. METHODS We describe the clinical profile in this case series of 11 patients with Ross syndrome and discuss the current status of autoimmunity in its pathogenesis and the management. RESULTS Of the 11 patients with Ross syndrome there was an almost equal sex distribution (male:female ratio was 1.17:1) and the mean age of onset of symptoms was 26 years. Patients took an average of 6 years to present to a tertiary center. Sixty-three percent of the patients presented with complaints of excessive sweating, whereas only 27% had complaints of decreased sweating over a particular area of the body. Only 45% of the patients had the complete triad of Ross syndrome, which included segmental anhidrosis, tonic pupil, and absent reflexes. Eighty-nine percent of the patients had documented absent sympathetic skin response on electromyography. The various markers of autoimmunity were negative in all patients who were investigated for the same in this series. Ninety percent of the patients were managed conservatively. CONCLUSIONS These findings suggest that, in Ross syndrome, generalized injury to ganglion cells or their projections are not purely autoimmune-mediated.

Cerebrotendinous xanthomatosis: Possibility of founder mutation in CYP27A1 gene (c.526delG) in Eastern Indian and Surinamese population

Cerebrotendinous xanthomatosis is a lipid storage disease characterized by diarrhea, cataract, tendon xanthoma and neurological regression if untreated. CYP27A1 is the only gene in which mutations are known to cause Cerebrotendinous xanthomatosis. We report two Indian families from different regions of India who underwent molecular testing of CYP27A1. The first family from Eastern India consisting of two affected individuals was found to have the c.526delG homozygous mutation in exon 3, previously reported from our laboratory, also in a patient from Eastern India. However the second affected individual from Southern India that we studied and two previously reported cases from Northern India have different mutations. Interestingly the only previous report of c.526delG mutation was in a Surinamese individual from the Netherlands. To date most of the pathogenic mutations for Cerebrotendinous xanthomatosis have been confined to single population except for R362C mutation which was reported from the Netherlands and the USA (Black). To our knowledge this is the second causal mutation for Cerebrotendinous xanthomatosis which has been reported in two different populations. As human trading was prevalent from Eastern India to Surinam by the Dutch settlers this mutation might suggest a common founder mutation in these populations.

SLEep among diabetic patients and their GlycaEmic control (SLEDGE): A pilot observational study: Sleep and glycemic control

Recent cohort studies have proven the association between sleep deprivation and adverse glycemic control (GC). The aim of this study was to assess the prevalence of excessive daytime sleepiness (EDS), a subjective measure of sleep deprivation, among type 2 diabetic mellitus (T2DM) patients and its association with GC.

Leprous neuromyositis: A rare clinical entity and review of the literature.

Mycobacterium leprae, the causative agent of leprosy (Hansens disease), is a slow growing intracellular acid-fast bacillus that affects the skin, peripheral nerves and respiratory tract. In patients with suppressed cell-mediated immunity, the infiltration of the Bacilli can produce disseminated illness such as leprous neuromyositis. We reported a case of 56-year-old gentleman presenting with pyrexia of unknown origin, asymmetric sensory motor axonal polyneuropathy and was on chronic exogenous steroid therapy. On evaluation, his skin, muscle, nerve and bone marrow biopsy showed numerous globi of acid-fast Bacilli suggestive of leprous neuromyositis, a rare form of disseminated Hansens disease. We reported this case in view of its rarity, atypical manifestation of a relatively rare disease and literature review on poor electrophysiological correlation in the diagnosis of leprous neuromyositis as compared to the histopathological examination.