Comorbidities in children with cerebral palsy: a single-centre cross-sectional hospital-based study from India.

OBJECTIVE: To describe the comorbidities in children with cerebral palsy (CP) and determine the characteristics associated with different impairments. DESIGN: Cross-sectional study. SETTING: Tertiary care referral centre in India. PATIENTS: Between April 2018 and May 2022, all children aged 2-18 years with a confirmed diagnosis of CP were enrolled by systematic random sampling. Data on antenatal, birth and postnatal risk factors, clinical evaluation and investigations (neuroimaging and genetic/metabolic workup) were recorded. MAIN OUTCOME MEASURES: Prevalence of the co-occurring impairments was determined using clinical evaluation or investigations as indicated. RESULTS: Of the 436 children screened, 384 participated (spastic CP=214 (55.7%) (spastic hemiplegic=52 (13.5%); spastic diplegia=70 (18.2%); spastic quadriplegia=92 (24%)), dyskinetic CP=58 (15.1%) and mixed CP=110 (28.6%)). A primary antenatal/perinatal/neonatal and postneonatal risk factor was identified in 32 (8.3%), 320 (83.3%) and 26 (6.8%) patients, respectively. Prevalent comorbidities (the test used) included visual impairment (clinical assessment and visual evoked potential)=357/383(93.2%), hearing impairment (brainstem-evoked response audiometry)=113 (30%), no understanding of any communication (MacArthur Communicative Development Inventory)=137 (36%), cognitive impairment (Vineland scale of social maturity)=341 (88.8%), severe gastrointestinal dysfunction (clinical evaluation/interview)=90 (23%), significant pain (non-communicating children's pain checklist)=230 (60%), epilepsy=245 (64%), drug-resistant epilepsy=163 (42.4%), sleep impairment (Children's Sleep Habits Questionnaire)=176/290(60.7%) and behavioural abnormalities (Childhood behaviour checklist)=165 (43%). Overall, hemiparetic and diplegic CP and Gross Motor Function Classification System ≤3 were predictive of lesser co-occurring impairment. CONCLUSION: CP children have a high burden of comorbidities, which increase with increasing functional impairment. This calls for urgent actions to prioritise opportunities to prevent risk factors associated with CP and organise existing resources to identify and manage co-occurring impairments. TRIAL REGISTRATION NUMBER: CTRI/2018/07/014819.

Clinical and molecular spectrum associated with Polymerase-γ related disorders.

BACKGROUND: POLG pathogenic variants are the commonest single-gene cause of inherited mitochondrial disease. However, the data on clinicogenetic associations in POLG-related disorders are sparse. This study maps the clinicogenetic spectrum of POLG-related disorders in the pediatric population. METHODS: Individuals were recruited across 6 centers in India. Children diagnosed between January 2015 and August 2020 with pathogenic or likely pathogenic POLG variants and age of onset <15 years were eligible. Phenotypically, patients were categorized into Alpers-Huttenlocher syndrome; myocerebrohepatopathy syndrome; myoclonic epilepsy, myopathy, and sensory ataxia; ataxia-neuropathy spectrum; Leigh disease; and autosomal dominant / recessive progressive external ophthalmoplegia. RESULTS: A total of 3729 genetic reports and 4256 hospital records were screened. Twenty-two patients with pathogenic variants were included. Phenotypically, patients were classifiable into Alpers-Huttenlocher syndrome (8/22; 36.4%), progressive external ophthalmoplegia (8/22; 36.4%), Leigh disease (2/22; 9.1%), ataxia-neuropathy spectrum (2/22; 9.1%), and unclassified (2/22; 9.1%). The prominent clinical manifestations included developmental delay (n = 14; 63.7%), neuroregression (n = 14; 63.7%), encephalopathy (n = 11; 50%), epilepsy (n = 11; 50%), ophthalmoplegia (n = 8; 36.4%), and liver dysfunction (n = 8; 36.4%). Forty-four pathogenic variants were identified at 13 loci, and these were clustered at exonuclease (18/44; 40.9%), linker (13/44; 29.5%), polymerase (10/44; 22.7%), and N-terminal domains (3/44; 6.8%). Genotype-phenotype analysis suggested that serious outcomes including neuroregression (odds ratio [OR] 11, 95% CI 2.5, 41), epilepsy (OR 9, 95% CI 2.4, 39), encephalopathy (OR 5.7, 95% CI 1.4, 19), and hepatic dysfunction (OR 4.6, 95% CI 21.3, 15) were associated with at least 1 variant involving linker or polymerase domain. CONCLUSIONS: We describe the clinical subgroups and their associations with different POLG domains. These can aid in the development of follow-up and management strategies of presymptomatic individuals.

Child survivor of rabies in India: a case report.

A 4-year-old boy was admitted with an acute onset fever for 4 days and drowsiness for 3 days, followed by progressive flaccid weakness of both lower limbs and encephalopathy soon after admission. He had sustained a WHO Class III stray dog bite 2 weeks previously and had received three doses of post-exposure rabies vaccination with purified vero cell vaccine but not rabies immunoglobulin. He was diagnosed with rabies based on the presence of rabies virus neutralising antibody in CSF (Day 1 1:128 and Day 26 1:2048) and typical findings on neuro-imaging. Rabies viral RNA was not detected in CSF, in saliva or on nuchal skin. The child survived with supportive treatment alone but he has extensive neurological sequelae. This report demonstrates the detailed clinico-investigative profile of a child who survived rabies following inadequate post-exposure prophylaxis and adds to the sparse knowledge of this usually fatal condition. ABBREVIATIONS: ADEM, acute disseminated encephalomyelitis; CBNAAT, cartridge-based nucleic acid amplification test; CSF, cerebrospinal fluid; EEG, electroencephalogram; GCS, Glasgow coma scale; EVM, eye opening, best verbal response, best motor response; IM, intramuscular; IVIg, intravenous immunoglobulin; MRC, Medical Research Council; MRI/FLAIR, magnetic resonance imaging/fluid attenuation inversion recovery; PCR, polymerase chain reaction; RFFIT, rapid fluorescent focus inhibition test; RIg, rabies immunoglobulin; RNA, ribonucleic acid; WBC, white blood cells; WHO, World Health Organization.

Acute lymphoblastic leukemia with treatment--naive Fanconi anemia.

Fanconi anemia is known to have a predisposition to cancer, mostly associated with acute myeloid leukemia. We report an eight year old girl with treatment and naive FA who developed acute lymphoblastic leukemia. She was initiated on chemotherapy but she failed to respond to treatment and died during induction phase of chemotherapy. While this association may be coincidental but possibility of transition of Fanconi anemia to ALL should be considered in view of high predisposition to cancer in this disorder.

A case of 9p deletion syndrome with Duane retraction syndrome.

The chromosome 9p deletion syndrome is a rare but specific clinical event. The clinical manifestations include dysmorphic facial features (trigonocephaly, midface hypoplasia, upward slanting palpebral fissures, and a long philtrum) and psychomotor retardation. Here we report a child with chromosome 9p deletion with Duane retraction syndrome, which has never been reported in the literature before.

Plasma volume, albumin, and fluid status in peritoneal dialysis patients.

BACKGROUND AND OBJECTIVES: Peritoneal dialysis (PD) patients may be overhydrated especially when inflammation is present. We hypothesized that patients with a plasma albumin below the median value would have measurable overhydration without a proportional increase in plasma volume (PV). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We investigated a cross-sectional sample of 46 prevalent PD patients powered to detect a proportional increase in PV associated with whole body overhydration and hypoalbuminemia. PV was determined from (125)I-labeled albumin dilution, absolute total body water from D dilution (TBW(D)), and relative hydration from multifrequency bioimpedance analysis (BIA; Xitron 4200) expressed as the extracellular water (ECW):TBW(BIA) ratio. RESULTS: Whereas patients with plasma albumin below the median (31.4 g/dl) were overhydrated as determined both by BIA alone (ECW:TBW(BIA) 0.49 versus 0.47, P < 0.036) and the difference between estimated TBW(BIA) and measured TBW(D) (3.55 versus 0.94 L, P = 0.012), corrected PV was not different (1463 versus 1482 ml/m(2), NS). Mean PV was not different from predicted, and its variance did not correlate with any other clinical measures. Multivariate analysis showed that the only independent predictor of whole body overhydration was reduced plasma albumin. CONCLUSIONS: Hypoalbuminemia is an important determinant of tissue overhydration in PD patients. This overhydration is not associated with an increased plasma volume. Attempts to normalize the ECW:TBW ratio in hypoalbuminemic, inflamed PD patients may lead to hypovolemia and loss of residual renal function.

The peritoneal osmotic conductance is low well before the diagnosis of encapsulating peritoneal sclerosis is made.

Encapsulating peritoneal sclerosis (EPS) is a serious condition whose frequency is increasing the longer the duration of peritoneal dialysis. To identify prognostic indicators of EPS, we studied here longitudinal changes in peritoneal membrane function of patients who later developed this complication. We identified all patients with an unequivocal diagnosis of EPS who began their peritoneal dialysis in our unit over a 20-year period and matched each of them for dialysis duration and age with four control patients who completed their dialysis. The dialysate/plasma creatinine ratio increased with time in both groups but was significantly higher in the patients with EPS only at the time their dialysis was discontinued. The ultrafiltration capacity was significantly worse for at least 2 years before stopping dialysis, diverging further at the time dialysis ceased, suggesting reduced osmotic conductance in the EPS patients. Both the glucose exposure rate for the 5 years preceding stoppage of dialysis and exposure to the osmotic agent icodextrin were significantly higher. Residual renal function was less in the EPS group, but there was no significant difference in the rates of peritonitis compared to the control group. The 24 h peritoneal protein clearance was not significantly different in EPS patients, possibly due to a greater fibrous matrix. Thus, our study shows that regular peritoneal membrane function tests can identify most patients at high risk of developing EPS before its occurrence.

A rare case of acute lymphoblastic leukaemia with hemophilia A.

A rare case of Acute lymphoblastic leukemia with hemophillia in a 12 year old boy is presented in the article. Patient was known case of hemophillia (factor VIII deficiency). He was diagnosed as a case of ALL based on bone marrow examination and immunophenotypic study. Patient was treated as per Children Cancer group guidelines. The main aim of reporting this rare association lies in developing treatment strategies in preventing life threatening bleeding due to this rare association which though may be accidental but need further research.

Long-term changes in solute and water transport.

The rate of transport of small solutes across the peritoneal membrane is one of the most important measurements in PD patients. Significant between-patient variability is associated with an impact on small solute clearance, ultrafiltration and even survival. Cross-sectional and longitudinal studies show that solute transport generally increases with time on treatment although this is again highly variable between individuals and is likely to represent an increased vascularity of the membrane. Initially, there is a coupled decrease in the ultrafiltration capacity of the membrane that can be explained by the earlier loss of the osmotic gradient leading predominantly to reduced free water transport via aquaporins combined with more fluid reabsorption once the osmotic gradient has dissipated. Subsequently, in some patients a further disproportionate fall in ultrafiltration occurs due to uncoupling of fluid transport from solute transport as a result of a reduction in the osmotic conductance of the membrane. Drivers of this damage appear to be peritonitis, glucose exposure and early loss of residual renal function. Cytokines and growth factors appear to be involved in this process and may prove useful biomarkers of membrane injury in the future.

Peritoneal protein clearance and not peritoneal membrane transport status predicts survival in a contemporary cohort of peritoneal dialysis patients.

BACKGROUND AND OBJECTIVES: Fast peritoneal membrane transport status may be due to inflammation or increased peritoneal membrane surface area. We evaluated the ability of peritoneal protein clearance (Pcl) to distinguish fast peritoneal membrane transport status as a consequence of peritoneal membrane inflammation and assess its impact on patient survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients who initiated peritoneal dialysis at our center since January 1998 and had a baseline peritoneal equilibration test, measurement of dialysis adequacy, and 24-h dialysate Pcl were included. Demography, comorbidities, and biochemical data were prospectively collected. Follow-up was until death or the end of the period studied. Multivariate regression analysis identified factors that were associated with Pcl. A Cox proportional hazards model was used to identify factors that were associated with survival. RESULTS: A total of 192 patients (56% men, mean age 54.3 +/- 15.3; 32% with diabetes) were included. On univariate analysis, Pcl was negatively correlated with serum albumin and positively correlated with age, dialysate/plasma creatinine ratio (D/Pcr), the presence of peripheral vascular disease, and urine volume. On multivariate analysis, serum albumin, D/Pcr, urine volume, and peripheral vascular disease remained significant. Predictors of mortality were age, comorbidity grade, and Pcl but not D/Pcr. CONCLUSIONS: In this cohort, peritoneal transport status no longer predicted survival, whereas Pcl remained a predictor. Increased large-pore protein loss may reflect the severity of underlying cardiovascular disease, portending a poor prognosis for these patients.

Peritoneal dialysis after a failed transplant.

Failed transplantation is an increasingly common cause for starting dialysis treatment. As with all patients approaching dialysis there is a need for adequate physical and psychological preparation and yet whilst by definition these individuals are known to health professionals this is not always achieved. It is likely that given adequate information, a significant proportion of these patients would prefer PD on lifestyle grounds. There is increasingly strong evidence that patients commencing PD after transplant failure enjoy overall survival and technique survival that is no different to those new to dialysis, even when other risk factors such as age, comorbidity, race, gender and membrane function are taken into account. The risk of peritonitis is also not different. These patients tend to lose residual renal function more rapidly but this does not translate into worse outcomes. The role and benefit in modulating immune suppressive drugs before and after commencing PD is not clear.