Rachna Seth

Vincristine-induced Neuropathy in Childhood ALL (Acute Lymphoblastic Leukemia) Survivors Prevalence and Electrophysiological Characteristics

The prevalence and the burden of vincristine-induced neuropathy have been poorly documented in childhood acute lymphoblastic leukemia survivors. This cross-sectional study was carried out at a tertiary care center in northern India from October 2011 to June 2012. Eighty consecutive acute lymphoblastic leukemia survivors aged 5 to 18 years, within 3 years of completion of their chemotherapy, were enrolled. After clinical evaluation, detailed nerve conduction studies were performed and the reduced version of the Total Neuropathy Score was calculated. The mean age at the time of evaluation was 11.2 ± 3.2 years. 33.75% had neuropathy electrophysiologically. Symmetric motor axonal polyneuropathy was the most common pattern of involvement seen in 19 (23.8%) children. There was significant improvement with time, as revealed by lower prevalence of neuropathy with increasing interval following vincristine injection. 33.75% of the children had Reduced version of Total Neuropathy Score ≥ 1.

Diagnostic criteria for Tuberculous Meningitis

Objective : Tuberculous Meningitis is associated with a high morbidity and mortality if there is a delay in diagnosis. The diagnosis is based on clinical evaluation since the bacteriological diagnosis takes time and has a low yield. This study attempts to validate these criteria in children with TBM.Methods : Forty-two children clinically suspected to have TBM were enrolled in the study. History, examination, CT scan and CSF findings were utilized to categorize patients into “definite”, “highly probable”, “probable” and “possible” TBM based on the criteria laid down by Ahuja et al. The validity of these criteria was tested against bacterial isolation and response to treatment.Results : Thirty one children, with complete data, were included for analysis. Using “improvement on therapy” as a criterion for definite TBM, we analyzed the sensitivity and specificity of the Ahuja criteria in diagnosing TBM. Using the criteria of “highly probable” TBM, the sensitivity was 65% with a specificity of 75%. When the criteria of “probable” TBM were used, the sensitivity increased to 96% while the specificity dropped to 38%. In an attempt to make these criteria more appropriate for children, we modified the criteria by including mantoux reaction, and family history of exposure in the criteria. The modified criteria gave a sensitivity of 83% and a specificity of 63%.Discussion : A sensitivity of 65% (highly probable group) implies that 35% of TBM patients will be missed, while the probable criteria gave a 63% false positive rate suggesting that the trade-off for a higher sensitivity makes the criteria very unreliable. Our modification of the criteria gave us a reasonable sensitivity of 83% with a higher specificity of 63%. The false positive rate was also reduced to 38%. Thus the modified Ahuja criteria worked better for children with TBM.Conclusion : The modified Ahuja criteria are better applicable for use in pediatric patients with TBM. Since the number of patients was small in this study, the study needs to be validated with a larger sample size

Clinical profile and outcome of swine flu in Indian children

ObjectiveTo describe the clinical characteristics and outcome of Indian children infected with 2009 H1N1 influenza virus.Study designRetrospective chart review.SettingOutpatient department and hospitalized patients in a tertiary care hospital.MethodsClinical details of 85 children (positive for the 2009 H1N1 virus infection tested by real-time reverse-transcriptase-polymerase-chain-reaction assay) were analyzed from medical charts.ResultsOf the 85 (55 boys) children positive for 2009 H1N1 virus infection, 64.7% were between 5 years to 16 years, and 35.3% were below 5 years age. The mean age of these children was 7.5±3.5 yr. Contact history was positive only in 22 (26%) cases. High grade fever was the most common symptom, followed by cough and rhinorrhea. Twenty-nine (34%) patients had an underlying co-morbid condition. Of the 34 patients who underwent chest radiography during evaluation, 18 children (52.9%) had findings consistent with lower respiratory tract infection. Antiviral therapy was initiated in 76 patients. Hospitalization was required in 30 (35.3%) children. Risk factors for hospitalization included underlying co-morbid condition, respiratory distress, vomiting, wheezing, diarrhea, hypotension and infiltrates/consolidation on chest radiograph. Mean length of hospitalization was 131±76 hours, irrespective of underlying disease. Three children developed Acute Respiratory Distress Syndrome and died.ConclusionsClinical features and routine laboratory investigations in children with swine origin influenza were non-specific. Children with co-morbid condition, respiratory distress, vomiting, wheezing, diarrhea, hypotension and infiltrates/consolidation on chest radiograph were at higher risk of hospitalization.

Clinical presentation and survival of retinoblastoma in Indian children

Objective To study the clinical presentation and survival among Indian children with retinoblastoma (RB) and to determine factors predictive of poor outcome. Methods A retrospective review of children newly diagnosed with RB at a tertiary referral centre was undertaken. Demographic and clinical characteristics and treatment outcomes were studied. Results A total of 600 patients (unilateral 67.6%, bilateral 32.4%) was studied. 61% was boys. The median age at presentation was 29 months (18 months vs 36 months in bilateral and unilateral cases, respectively, p<0.001). leukocoria was most common (83%), followed by proptosis (17%). Tumours were intraocular in 72.3% and extraocular in 27.7% cases. In the intraocular group, 78% were advanced Group D or E disease. Metastasis to the central nervous system was noted in 15.7% of extraocular cases. A statistically significant difference was seen between intraocular and extraocular groups in the median age (24 months vs 37.5 months, p<0.001) and median lag period (2.5 months vs 7 months, p<0.001). The Kaplan-Meier survival probability was 83%, 73% and 65% at 1 year, 2 years and 5 years, respectively. On univariate analysis, age >2 years (p=0.002), lag period >6 months (p=0.004) and extraocular stage (p<0.001) were associated with poor outcome. On multivariate analysis, extraocular invasion was predictive of low survival (HR 5.04, p<0.001). Conclusions Delayed presentation is a matter of concern. Improving awareness about the early signs and creating facilities for diagnosing and treating RB at the primary and secondary levels of healthcare are required to reduce mortality and morbidity, and lead to improved outcomes that are comparable with the developed nations.

Clobazam in refractory childhood epilepsy

ObjectiveTo evaluate the efficacy of clobazam in childhood refractory epilepsy and to characterize the adverse drug reaction profile in the Indian population.MethodsA cohort of 88 children with ‘refractory’ epilepsy was started on clobazam as add-on therapy. Diagnosis was established and seizure type recorded. Therapeutic response was recorded as ‘complete’, ‘good’, and ‘no response’. Observed side effects were classified as ‘mild’, ‘moderate’ and ’severe’.ResultsMost children were on at least two antiepileptics. Seizures most identified were either partial (36.3%) or generalized tonic-clonic (15.9%). The dose ranged from 0.3–2 mg/kg/day (average 1+0.2 mg/kg/day). Clobazam was effective against all seizure types with complete seizure control seen in 60.2% patients. Tolerance was seen in 5 (5.6%) patients. Side effects were seen in 23 (26%) patients and were ‘mild’ in 20 (86.9%) of them. Clobazam was stopped in three patients who developed ataxia, which resolved on stopping the drug.ConclusionClobazam was observed to be an effective broad-spectrum antiepileptic with ‘mild’ side effects in Indian children.

Management of Common Oncologic Emergencies

The common oncologic emergencies include Superior Vena Cava Syndrome (SVCS) and Superior Mediastinal Syndrome (SMS), Tumor Lysis Syndrome (TLS), Hyperleukocytosis and Febrile Neutropenia. SVCS denotes compression, obstruction or thrombosis of SVC and SMS denotes SVCS and tracheal compression. The diagnosis should be established early with minimum invasive techniques. Steroids should be administered immediately. Sedatives are contraindicated. TLS describes the metabolic derangements in various combinations that include hyperuricemia, hyperphosphatemia, hyperkalemia hypocalcemia and uremia which arise from death of and release of contents from tumor cells. Early recognition of patients at risk and initiation of preventive therapy for TLS is essential. Treatment is directed at adequate hydration, use of allopurinol and alkalinization of urine. Hyperluekocytosis is defined as peripheral leukocyte count exceeding 100,000 per microlitre and therapy is tailored at reduction of blood viscosity with hydration, alkalinization of urine allopurinol; chemotherapy should be started once the child is metabolically stable. Febrile neutropenia is a common oncologic emergency directly related to the immune suppression related to cancer treatment. Successful outcome depends on careful evaluation, identification of cause and prompt treatment with antimicrobials (empirical/directed to a specific focus).

Unilateral proptosis and extradural hematoma in a child with scurvy

We report a 3-year-old boy with unilateral proptosis, painful swelling of the right thigh and aphasia. He had radiographic evidence of scurvy in the limbs and bilateral frontal extradural hematomas with a mass lesion in the left orbit on MRI. He was treated with vitamin C and on follow-up 8 weeks later had recovered with no evidence of the orbital mass on clinical or radiological study. Scurvy manifesting as proptosis and extradural hematoma is rare.

Chronic hepatitis E – an emerging disease in an immunocompromised host

Abstract Chronic hepatitis E virus (HEV) infection is increasingly being reported in immunosuppressed individuals with HIV, patients with haematological malignancy and transplant recipients. The diagnosis of cirrhosis and liver failure post chronic HEV is controversial due to lack of standard diagnostic criteria. The treatment benefits of ribavirin in chronic HEV of genotype 1 are not well reported. We report a case of chronic HEV infection of genotype 1 leading to chronic liver disease in a child cured of acute leukaemia. Our report also highlights the successful use of ribavirin for eradicating chronic HEV infection and its subsequent survival benefits. Chronic hepatitis E may be an emerging disease of immunosuppressed patients and should be suspected in the presence of cryptogenic transaminitis. Ribavirin is an effective therapy for controlling HEV.

Primary cutaneous mucormycosis during induction chemotherapy in a child with acute lymphoblastic leukemia

We report a child with acute lymphoblastic leukemia who developed primary cutaneous mucormycosis at the site of lumbar puncture during induction chemotherapy. Though high mortality rates are reported with invasive mucormycosis, prompt biopsy, early identification and antifungal therapy using a combination regime of amphotericin-B and rifampicin along with extensive surgical debridement led to complete cure of the lesions in the index case.

Immunophenotypic analysis of T‐acute lymphoblastic leukemia. A CD5‐based ETP‐ALL perspective of non‐ETP T‐ALL

T‐cell antigens [CD5,CD1a,CD8] define early T‐cell precursor acute lymphoblastic leukemia (ETP‐ALL). To understand immature T‐ALL of which ETP‐ALL is part, we used these antigens to subcategorize non‐ETP T‐ALL for examining expression of myeloid/stem cell antigens (M/S) and clinical features. Using CD5 (+/−) to start categorization, we studied 69 routinely immunophenotyped patients with T‐ALL. CD5− was a homogenous (CD8,CD1a)− M/S+ ETP‐ALL group (n = 9). CD5+ cases were (CD8,CD1a)− pre‐T‐ALL (n = 22) or (CD8,CD1a)+ (n = 38) thymic/cortical T‐ALL; M/S+ 20/22 (90.91%) in former and 22/38 (57.89%) in latter (P = 0.007). ETP‐ and pre‐T‐ALL together (CD1a−,CD5−/+ immature T‐ALL group) were nearly always M/S+ (29/31; 93.55%). In multivariate analysis, only ETP‐ALL predicted poor overall survival (P = 0.02). We conclude (i) CD5 negativity in T‐ALL almost always means ETP‐ALL. CD1a and CD8 negativity, as much as CD5, marks immaturity in T‐ALL, and the CD5+/−/CD1a−/CD8− immature T‐ALL group needs further study to understand the biology of the T‐ALL–myeloid interface. (ii) ETP‐ALL patients may be pre‐T‐ALL if CD2+; CD2+, conversely, CD5−/CD1a−/CD8− pre‐T ALL patients are ETP‐ALL. (iii) Immunophenotypic workup of T‐ALL must not omit CD1a, CD5, CD8 and CD2, and positivity of antigens should preferably be defined as recommended for ETP‐ALL, so that this entity can be better evaluated in future studies of immature T‐ALL, a group to which ETP‐ALL belongs. (iv) ETP‐ALL has poor prognosis.