Indar Kumar Sharawat

Evaluation of Risk Factors Associated with First Episode Febrile Seizure

INTRODUCTION Febrile seizure (FS) is the single most common type of seizure seen in children between 6 months to 5 years of age. The purpose of our study was to identify the risk factors associated with the first episode of febrile seizures, which would help in the better management and preventive measures in children at risk for FS episodes. AIM To evaluate the risk factors associated with the first episode of febrile seizures in Indian children. MATERIALS AND METHODS This was a hospital based, case control study. The purpose of this study was to identify the risk factors associated with the first FS episode in children. Seventy (70) children between age 6 months to 5 years with their first episode of FS were compared with 70 children with fever but without seizures based on various risk factors. RESULTS The mean age was 24.90±16.11 months in cases and 26.34±16.93 months in controls. Male: female ratio was 2:1. A positive family history was found in 31.4% of first degree and 11.4% in second degree relatives. Mean maximum temperature was 102.06±1.1°F and URI (upper respiratory infection) was most common cause of fever. Antenatal complication was significantly higher in the case group. RBC (Red Blood Cells) indices like lower mean haemoglobin, MCV (Mean Corpuscular Volume), MCH (Mean Corpuscular Haemoglobin concentration) and higher RDW (Red Cell Distribution Width) values were seen in patients. Serum sodium, Serum calcium and random blood sugar values of the cases were significantly lower than those of controls (p<0.05). CONCLUSION Our study shows that male gender, family history of febrile seizures, peak body temperature, underlying cause of fever, antenatal complications, low serum calcium, sodium, blood sugar and microcytic hypochromic anaemia are the risk factors associated with the occurrence of first episode of febrile seizure and, thus, preventive measures in removing these risk factors could lead to a decrease in incidence of FS.

Topiramate Therapy in Alternating Hemiplegia of Childhood

To the Editor: In a recent publication from our centre, we had highlighted novel features in a child with Alternating hemiplegia of childhood (AHC) [1]. We would like to share our experience with the use of topiramate in the management of an another genetically confirmed child with the same disorder. A 14-mo-old girl presented with concerns of global developmental delay (6–8 mo) and paroxysmal episodes of tonic/dystonic spells of the neck and upper limb since three months of age. She was first born to non-consanguinous parents after an uneventful perinatal period. Her family history was unremarkable. At eight months of age, she developed recurrent episodes of flaccid hemiparesis of either side of the body. These episodes were acute with no effect on consciousness and used to subside by two days. On examination, the child had normal head circumference with normal consciousness and flaccid weakness of left upper limb more than lower limb. The clinical possibilities considered at admission were Alternating hemiplegia of childhood; mitochondriocytopathy and GLUT1 deficiency. Magnetic resonance imaging of the brain was unremarkable. Electroencephalography was normal. Blood lactate was 2.3 mmol/L. CSF: serum glucose ratio was 0.8. Next generation sequencing revealed a heterozygous missense variation in exon 17 of the ATP1A3 gene {c.2401G > G/A;p.Asp801Asn} and its pathogenicity was confirmed by insilico analysis. The child was started on first line flunarizine therapy, however, the episodes were refractory. The child was then initiated on topiramate therapy, following which there was dramatic improvement in paroxysms. On 6 mo follow-up, posttopiramate therapy, child has language predominant delay with no further episodes of dystonic spells or flaccid hemiparesis. AHC is a devastating disease and challenging to manage. Flunarizine has demonstrated promising results with efficacy in 76% patients [2]. Topiramate has also been proposed as a promising alternative in flunarizine refractory AHC. The use of topiramate was first proposed byDi Rosa et al. in a 12-y-old girl with family history of migraine with sustained response over 18 mo follow-up [3]. The pharmaco-therapeutic mechanism of topiramate in AHC is unknown but may be related to inhibition of non NMDA, especially the AMPA mediated excitatory neurotransmission [4]. However, the drug efficacy is difficult to evaluate owing to the ‘roller-coaster’ course of AHC, with periods of aggravation and improvement. In conclusion, we would like to highlight the promising role of topiramate in Alternating hemiplegia of childhood.

Skeletal Maturation and Mineralisation of Children with Moderate to Severe Spastic Quadriplegia

INTRODUCTION Diminished bone mineral density and delayed skeletal maturation are common in children with spastic quadriplegia. AIM The purpose of our study was to evaluate the Bone Mineral Density (BMD) of children with moderate to severe spastic quadriplegia and its relationship with other variables like nutrition and growth. MATERIALS AND METHODS This was a hospital based, cross- sectional, case-control study. Forty-two (28 males, 14 females) children with spastic quadriplegia and 42 (24 males, 18 females) healthy children were included in the study. BMD of cases and control were measured by Dual Energy X-ray Absorptiometry (DEXA). Radiographs of left hand and wrist of cases and controls were taken and bone age was determined. RESULTS BMD values of upper extremity, lower extremity, thoraco-lumbar spine and pelvis in cases were lower than those of controls (p <0.0001). In children with non severe malnutrition, 75% of the cases had lower bone age than chronological age, whereas all cases with severe malnutrition had lower bone age than chronological age. Step wise regression analysis showed that nutritional status independently contributed to lower BMD values but the BMD values did not correlate significantly with the use of anticonvulsant drugs and presence of physical therapy. CONCLUSION Decreased BMD and delayed bone age is prevalent in children with spastic quadriplegia and nutritional status is an important contributing factor.

Risk Factors for Steroid Dependency in Children with Idiopathic Nephrotic Syndrome in India

To the Editor: Minimal change nephrotic syndrome (MCNS) is the most common cause of idiopathic nephrotic syndrome (INS) with a 2:1 predilection for boys. INS has a more favourable prognosis and is characterised by steroid responsiveness in approximately 90 % of patients [1, 2]. The incidence of relapse rate is high and approximately half of them develop steroid dependency. Many predictors of steroid dependency have been proposed i.e., duration from initial steroid therapy to response, concomitant upper respiratory tract infection during relapse, relapse during the first half year after disease onset, low serum protein level, gender, age at onset, total cholesterol and steroid regimen used. We conducted our study to determine the predictive risk factors for development of steroid dependency in children with INS. The records of 125 children with steroid responsive INS were retrospectively studied; out of which 38 children (23.4 %) were steroid dependent. It was found that time duration of remission (<10 d) from start of therapy (p 0.00, OR= 1.1, 95 % CI=1.0–1.1) and steroid regime other than 6 wk daily (2 mg/kg)+6 wk alternate day (1.5 mg/kg) (p 0.01, OR= 5.6, 95 % CI=1.3–24.3) were found as significant predictors. The relapsing nature of the disease presents a major challenge, and 60 % of the patients have a high relapse rate [3], with a subsequent risk of steroid toxicity and complications and with half of those relapsing eventually becoming steroid dependent [4]. By early identification of those children who are likely to develop steroid dependency and its attendant morbidity, the attending clinician will be able to plan the long term management of these children and minimizing the steroid side effects.

Mystery Case: Tortuous hairs and tortuous blood vessels

A 5-month-old boy, born to a third-degree consanguineous couple, presented with drug-refractory seizures. On examination, he had microcephaly, abnormal scalp hairs (figure 1A), loose skin folds (figure 1B), and generalized hypotonia. Based on hair microscopy (figure 1, C and D), radiologic findings (figure 2, A–D), and a pathogenic mutation in the ATP7A gene (c.4006-1G>C, intron 20), a diagnosis of Menkes disease was confirmed.

Recurrent encephalopathy in milliary neurocysticercosis: An uncommon manifestation of a common infection

Neurocysticercosis is a common parasitic infection in children in developing countries and neurological symptoms such as seizures are the most common manifestations. However, symptoms of encephalopathy are an unusual presentation in children. A 4-year-old boy presented with recurrent episodes of febrile encephalopathy. His magnetic resonance imaging of the brain was suggestive of milliary neurocysticercosis of various stages. Reports on recurrent encephalopathy following neurocysticercosis are scarce in literature. Hence, we report this case who presented with recurrent episodes of encephalopathy.

Recurrent Streptococcus pneumoniae meningitis and Mondini dysplasia: Association or causation?

Mondini dysplasia is a developmental disorder of the inner ear structures and it is a rare cause of recurrent bacterial meningitis in children. A 10-year-old boy presented with acute febrile encephalopathy and right ear pain. In the past, he had suffered from two distinct episodes of pyogenic meningitis. On examination, he had signs of meningeal irritation and right ear sensorineural deafness. Magnetic resonance imaging of the brain and computerized tomography of the temporal bone was suggestive of Mondini dysplasia in the right ear. Our case highlights the need for (a) screening of hearing loss at the bedside by Rinne and Weber test in case of recurrent bacterial meningitis (b) searching for an underlying inner ear malformation if there is a hearing loss.

Child with Progressive Hemiparesis: Think Beyond Neoplastic Disorders

To the Editor:A 7-year-old, previously asymptomatic and developmentally normal, right-handed boy presented with progressive difficulty in using the right half of the body. He had a progressively worsening limp and progressive difficulty in using his right upper limb, such that he was unable to write or eat with his right hand. He had also developed slurring of speech and reduced fluency. He had intermittent episodes of emotional outbursts and aggression. However, his intellect was preserved and he was interacting well with parents. There was no history of hearing or visual impairment; seizures; involuntary movements; squint; or symptoms suggestive of raised intracranial pressure. He was first born to a non-consanguineous couple. The family history was non-contributory. On examination, he had normal head size, normal fundii, spastic dysarthria, right-sided lower facial palsy. He had bilateral, asymmetrical pyramidal signs (more on right side). A possibility of intracranial space occupying lesion was clinically considered. A magnetic resonance imaging (MRI) of the brain r e ve a l ed b i l a t e r a l , a s ymme t r i c a l ch ange s i n periventricular white matter and splenium of the corpus callosum (Fig. 1). A sequencing of ABCD1 gene using next generation sequencer revealed a pathogenic hemizygous variant (c.1390C > T) in exon 4 confirming the diagnosis of X-linked Adrenoleukodystrophy. Supportive care was initiated and the family was counseled for genetic testing of the younger asymptomatic brother. X-linked Adrenoleukodystrophy (ALD) is a genetically determined disorder involving the metabolism of Very Long Chain Fatty Acids [1]. The childhood form of ALD usually presents with initial symptoms which include hyperactivity, worsening school performance and reduced auditory discrimination [2]. It progresses rapidly with increasing spasticity and paralysis; visual and hearing loss; and progressive dysfunction of speech and swallowing leading to a vegetative state [3]. Usually, it presents with symmetric neurological signs and symptoms. However, asymmetric involvement has been documented in about 5% children [4] and 10% children have early frontal lobe involvement [5]. Atypical presentation in ALD includes; progressive hemiparesis and focal seizures, but, eventually all patients have bilateral * Naveen Sankhyan drnsankhyan@yahoo.co.in

Post-Herpetic Autoimmune Encephalitis

To the Editor: A previously healthy 8-y-old boy presented with fever, generalized seizures, and progressive lethargy for the past 4 d. On examination, he had altered sensorium, meningismus, and brisk muscle stretch reflexes. There were no focal motor deficits or papilledema. A clinical diagnosis of acute meningoencephalitis was considered. Cerebrospinal fluid examination showed 268 cells (74% lymphocytes), normal glucose, elevated protein (217 mg%), absence of red blood cells and positive Herpes simplex virus (HSV)-DNAPCR. Themagnetic resonance imaging (MRI) brain was suggestive of changes seen in herpes encephalitis (Fig. 1). Electroencephalograph showed bilateral slowing with no epileptiform discharges. Intravenous acyclovir (60 mg/kg/day) was administered for 21 d. At discharge, he had residual cognitive and speech impairment. Two weeks later (nearly 40 d after the onset of encephalitis), he returned with severe behavioral abnormalities; rapid on-off state between responsiveness and nonresponsiveness (light-switch mental status); mutism with intermittent echolalia; hyperorality; social disinhibition; acral dyskinesia; and irritable insomnia. A clinical diagnosis of herpes relapse or secondary immune-mediated disorder was considered. A repeat electroencephalography showed diffuse slowing. A repeat cerebrospinal fluid examination showed no cells, normal biochemistry, negative HSV DNA-PCR and strongly reactive anti-N-methyl-D-aspartate receptor (NMDAR) antibodies on cell based assay (Fig. 1c). He recovered significantly with intravenous pulse methylprednisolone and immunoglobulin therapy. Our case highlights the importance of recognizing postherpetic autoimmune encephalitis in children as the treatment is entirely different and needs to be initiated early for improved neurological outcome. Anti-NMDAR antibodies are being increasingly described in children with herpes encephalitis and can mimic a viral encephalitis relapse [1]. This immune activation and generation of anti-NMDAR antibodies is possibly related to the virus-induced neuronal destruction exposing the NMDAR or polyspecific B-cell activation occurring in the course of herpes-related central nervous system inflammation [1]. This secondary (postherpetic) anti-NMDAR encephalitis is associated more frequently with movement disorders than with seizures. The presence of new behavior abnormalities, insomnia, light switch mental status, movement disorder, mutism and absence of seizures are pointers to an underlying autoimmune phenomenon as in the index case [2, 3]. The clinical suspicion is supplemented by negative HSV DNA PCR, poor response to acyclovir and lack of new lesions in MRI [4]. The key to management is timely commencement of immune-modulatory therapy to improve neurological outcomes. A better understanding of this subgroup of herpes encephalitis triggered anti-NMDAR antibodies is needed for more targeted therapy. * Naveen Sankhyan drnsankhyan@yahoo.co.in

Acute Flaccid Paralysis: Intravenous Immunoglobulin is Not the Drug of Choice Always!

To the Editor: A 7-y-old boy presented with a history of pain in the limbs for 10 d, which was characteristically more during the evening and night, and weakness of all 4 limbs for 5 d. There was no history of altered sensorium, seizures, preceding episode of loose stools or upper respiratory tract infection, trauma, tick bite, dog bite or rash. On examination, he had normal mentation and right lower motor neuron facial nerve palsy. His power in right upper and both lower limbs were 3/5 and in left upper limb, it was 4/5 at all the joints. Muscle stretch reflexes were absent. Sensory and cerebellar examination was normal. He had neck stiffness and positive Kernig’s sign. Clinical diagnosis of meningoradiculitis and atypical presentation of Guillian Barré syndrome was made. Nerve conduction revealed motor axonal polyneuropathy. MRI whole spine revealed post contrast enhancement of dorsal and ventral roots suggestive of radiculitis (Fig. 1a-e]. Cerebrospinal fluid (CSF) examination showed pleocytosis (80 cells/mm, 100% lymphocytes), elevated protein (105 mg/dl) and normal sugar (45.6 mg/dl). CSF culture was sterile. CSF picture compelled us to send for Lyme’s and HIV serology; HIV was non-reactive, however Lyme’s serology was strongly positive (Serum IgM, IgG antibody levels were 40.79 aU/ml, 7.37aU/ml respectively). A diagnosis of Lyme’s meningoradiculitis was concluded. The child was started on intravenous ceftriaxone for two weeks. After 2 wk, power was 4/5 in all the 4 limbs and there were no meningeal signs. Neurological manifestations (Neuroborreliosis) is seen in about 10% of patients with Lyme disease and it includes cranial neuropathy, mononeuritis multiplex, radiculitis and lymphocytic meningitis. Index child was fulfilling the criteria for Lyme’s meningoradiculitis, which in fact is the most frequent manifestation of early disseminated Lyme’s disease [1]. In our patient we could not test CSF antibodies to Lyme’s in view of economic constraints. Some patients can reveal negative serology in their serum [2, 3] or even no CSF synthesis of specific immunoglobulins [4]; however absence of both does not necessarily rule out Lyme meningoradiculitis [2–4]. The diagnosis of Lyme meningoradiculitis should be suspected in all patients with suspicion of GBS who are residing in endemic regions and present with radicular pains preceding the weakness, predominant signs of meningeal irritation, unilateral or bilateral facial nerve involvement with or without a lymphocytic CSF picture as therapy is different and rewarding and if picked early, can prevent significant neuromorbidity and unnecessary costly therapies like immunoglobulins.