Association Of Child Neurology, India

Coppola G et al. Current role of rufinamide in the treatment of childhood epilepsy: Literature review and treatment guidelines. Eur J Paediatr Neurol 2014 May 28. [Epub ahead of print]

The literature on the efficacy and safety of rufinamide in childhood-onset epilepsy syndromes currently includes approximately 600 paediatric patients.

Purpose:The literature on the efficacy and safety of rufinamide in childhood-onset epilepsy syndromes currently includes approximately 600 paediatric patients.

Results:Rufinamide is effective in decreasing the seizure frequency in the Lennox-Gastaut syndrome (LGS), especially tonic and atonic seizures. It might consequently be preferred to other drugs as a second-line treatment for LGS when drop-attacks are frequent. The mean responder rate in the published studies is 38% with seizure freedom achieved in 2.4% of patients. Rufinamide has shown some efficacy in epileptic encephalopathies other than LGS. It can be also effective as adjunctive therapy in children and adolescents with drug-resistant partial seizures. The available data suggest that rufinamide has an acceptable risk/benefit ratio with quite a low risk of aggravating seizures. Common adverse effects (somnolence, nausea and vomiting) are usually mild and self-limiting; they are more frequently observed during titration than in the maintenance phase, suggesting that low escalation rates might be associated with fewer adverse effects. Rufinamide appears to have a favourable cognitive profile compared with other antiepileptic drugs.

Conclusions and comment: This paper summarizes the views of a panel of experienced European epileptologists with regard to the current role of rufinamide in the treatment of childhood epilepsies. Rufinamide is only approved for adjunctive treatment of seizures associated with LGS in children 4 years of age and older. There are very few data on rufinamide treatment at the onset of LGS or early in the course of the disorder; whether early treatment will improve outcome has yet to be determined.

Chiang SS et al. Treatment outcomes of childhood tuberculous meningitis: a systematic review and meta-analysis. Lancet Infect Dis. 2014 Aug 6. pii: S1473-3099(14)70852-7. doi: 10.1016/S1473-3099(14)70852-7. [Epub ahead of print]

Methods: A systematic review and meta-analysis of childhood tuberculous meningitis studies published up to Oct 12, 2012. Included study reports that applied predefined diagnostic criteria and described treatment regimens and outcomes. Pooled risks of death during treatment and neurological sequelae among survivors is presented.

Findings: 19 studies met the inclusion criteria, with reported treatment outcomes for 1636 children. Risk of death was 19·3% (95% CI 14·0-26·1) and probability of survival without neurological sequelae was 36·7% (27·9-46·4). Among survivors, risk of neurological sequelae was 53·9% (95% CI 42·6-64·9). Diagnosis in the most advanced disease stage (3) occurred in 307 (47%) of 657 patients and was associated with worse outcomes than was earlier diagnosis. The most common findings at presentation were cerebrospinal fluid (CSF) leucocytosis (frequency 99·9%, 95% CI 68·5-100·0), CSF lymphocytosis (97·9%, 51·9-100·0), fever (89·8%, 79·8-95·2), and hydrocephalus (86·1%, 68·6-94·6). Frequency of CSF acid-fast-bacilli smear positivity was 8·9% (95% CI 5·0-15·4), and frequency of CSF culture positivity for Mycobacterium tuberculosis was 35·1% (16·8-59·2).

Comment:This is study which collates data of last several decades. This meta-analysis provides the framework to compare emerging data on outcome of TBM. Despite treatment, childhood tuberculous meningitis has very poor outcomes. Poor prognosis and difficult early diagnosis emphasise the importance of preventive therapy for child contacts of patients with tuberculosis and low threshold for empirical treatment of tuberculous meningitis suspects. Implementation of consensus definitions, standardised reporting of data, and high-quality clinical trials are needed to clarify optimum therapy.

Neonate with seizures

Aicardi Goutiere Syndrome: A case report

A four-year old boy, first child born to second-degree consanguineous couple presented with developmental delay, microcephaly and recurrent seizures from age of 5 months. The antenatal and perinatal periods were uneventful. He had episodes of fever associated altered sensorium and seizures for 1-2 weeks from 5 months onwards every 2-3 months. He had been treated as meningoencephalitis (previous reports not available). No family history of mental retardation or early childhood deaths. On examination, hypertelorism with horizontal oscillatory nystagmus, spasticity were noted. Rest of the examination was normal. Developmental evaluation gave developmental age of 6 months.

CSF analysis revealed lymphocytosis, with normal protein and glucose. No organisms were detected and negative for TORCH studies. CT scan (Fig. 1) and MRI of the brain (figure 2) are given below. The clinical and radiological findings in our patient, together with the CSF findings of an elevated lymphocytosis are highly suggestive of Aicardi- Goutiere’s syndrome.

AGS is an autosomal recessive progressive encephalopathy associated with basal ganglia calcification, white matter abnormality, CSF pleocytosis, and elevated CSF interferon- α. The main radiological differential diagnosis includes Cockayne syndrome, congenital infections, in particular congenital cytomegalovirus infection and toxoplasmosis and pseudo-TORCH syndrome.

Figure 1: CT scan showing spotty/punctate calcification in the basal ganglia, periventricular regions, parietal regions and cerebellar lobes bilaterally. Diffuse hypodense areas in bilateral frontal, parietal and temporal regions white matter. The cortical sulci, basal cisterns, and ventricular system are prominent, suggestive of cortical atrophy.

Figure 2: MRI scan of the brain showed diffuse symmetric, bilateral, white matter hyperintensities on T2-weighted images and T1 W images (Fig. 2) predominantly in the bilateral frontal, parietal and temporal subcortical white matter regions with paucity of white matter. Well defined cysts noted in the bilateral frontal and temporal regions. Thin rim of corpus callosum was seen.

Marin Amat sign

Dr. Puneet Jain and Dr. Sheffali Gulati,
Division of Pediatric neurology, All india institute of medical sciences (AIIMS), New delhi.
Email: puneet_mpa@yahoo.com

A premorbidly normal, 8-years old girl presented with 5 days- history of deviation of angle of mouth towards right side and incomplete closure of the left eye. There was no history of ear discharge/vesicles, decreased hearing or parotid swelling. There was no history s/o other cranial nerve deficits, altered sensorium, seizures, headache, vomiting, weakness, sensory loss or unsteadiness. Examination revealed left CN VII palsy and Marin Amat sign. Fundoscopy and otoscopy was normal. Her MRI Brain was normal. Marin Amat sign, also called as “reverse Gunn phenomenon” is a synkinesia, seen with Bells palsy, due to aberrant regeneration of the facial nerve. (The video is available on personal request to the author)

Figure: Figure showing left facial nerve palsy

EEG pattern in a child with Lissencephaly

Puneet Jain, Suvasini Sharma, Satinder Aneja

Pediatric Neurology, Department of Pediatrics, Kalawati Saran Children’s Hospital (LHMC), ew Delhi, India.

Email: puneet_mpa@yahoo.com

An eight month old male presented with developmental delay and epileptic spasms for the last 3 months. He was the first child of non-consanguineous marriage. The antenatal and perinatal periods were uneventful. He achieved social smile at 5 months, partial neck holding at 6 months and was recognizing his mother and cooing at the time of presentation. There was no grasp. There was no regression of attained milestones. He started having flexor spasms since last 3 months. The spasms occurred in clusters which occurred mainly on waking up from sleep. He also had stiffness in the lower limbs which had been noticed for the last 2 months. This was non-progressive. Vision and hearing were normal. The family history was unremarkable.

On examination, the child had normal facies and no neurocutaneous markers. The weight and length were age appropriate. He had microcephaly (OFC 40 cm). The cranial nerve examination was normal. The tone was increased in all 4 limbs with brisk deep tendon reflexes and extensor plantar responses. Systemic examination was unremarkable. The MRI of the brain showed Lissencephaly with no gradient (Fig). The EEG showed diffuse high voltage alpha-frequency activity intermingled with beta-frequency activity (Fig).

Lissencephaly is a disorder of neuronal migration characterized by absent or abnormally wide gyri and abnormally thick cortex. Epilepsy is a major presentation of Lissencephaly syndromes and is usually drug-refractory. Three EEG patterns have been classically described in patients with Lissencephaly. The current case showed EEG pattern I. The characteristic EEG patterns along with the clinical findings may help neurologists to consider the diagnosis of Lissencephaly.

Suggested Reading

Menascua S, Weinstockb A, Farooq O, Hoffman H, Cortez MA. EEG and neuroimaging correlations in children with Lissencephaly. Seizure 2013;22:189-193

Isolated Pontine Involvement in Evolving Posterior Reversible Encephalopathy Syndrome

Ramesh Konanki, Lokesh Lingappa
Rainbow Hospital for Women and Children, Hyderabad

Email: rameshkonanki@gmail.com

A 8-year old previously healthy boy presented with fever, vomiting, bleeding gums and later, seizures on day 14 of illness. Child was noted to have hypertension, thrombocytopenia, hemolytic anemia, uremia and elevated serum lactate dehydrogenase suggestive of atypical hemolytic-uremic syndrome. He had repeated seizures and encephalopathy from day 14, requiring three antiepileptic drugs. The CT scan of brain on day 14 showed bulky, hypodense pons with normal supratentorial structures (figure 1A). MRI two days later showed hyperintensities involving pons and cerebellar peduncles (figure 1B). Repeat CT scan three days after MRI showed involvement of bilateral parietooccipital regions along with bulky pons (figure 1C). The hypertension, uremia, seizures and encephalopathy improved gradually with plasmapheresis. Repeat CT scan six weeks later showed complete resolution of signal changes in pons and parietooccipital regions, confirming the diagnosis of PRES.

Figure 1.

• CT scan on day 14 showing bulky, hypodense pons with obliteration of cisternal spaces (arrows);
• T2-weighted MRI on day 16 showing hyperintensities of pons and middle cerebellar peduncles (block arrows);
• CT scan on day 19 showing hypodensities asymmetrically involving parieto occipital regions (unshaded arrows)

Neonate with Seizures and Encephalopathy

Ramesh Konanki, Lokesh Lingappa
Rainbow Children’s Hospital & Perinatal Centre, Hyderabad

A 5-day old baby girl, born at term gestation to 3rd degree consanguineous couple, appropriate for gestation, was admitted with complaints of seizures, poor feeding and lethargy. The peripartum was uneventful. At admission, baby was in peripheral circulatory failure, encephalopathy and respiratory distress. Baby was treated with antibiotics, antiepileptics (Phenobarbitone and Fosphenytoin), and mechanical ventilation. Investigations revealed metabolic acidosis, hyperammonemia (520 m.mol/l), arterial lactate 2.8 m.mol/l and hypoglecemia. Urine ketones were negative. The EEG showed diffuse cerebral dysfunction (Low amplitude indeterminate activity) with electrographic seizures and frequent brief ictal rhythmic discharges (BIRDs) arising from both hemispheres independently. Based on lab investigations and imaging findings possibility of IEM was considered. MRI images are given below. The blood amino acids and acylcarnitine profile (by TMS) revealed markedly elevated propionyl carnitine (C3), and elevated C3/C2 and C3/C16 ratios suggestive of methyl malonic academia/propionic acidemia.

Radiological differential diagnoses include ethyl malonic aciduria, 3-methyl glutaric aciduria, beta-keto thiolase deficiency, maple syrup urine disease (MSUD) and Leigh’s disease.

Figure 1: Axial T1-Weighted MRI showing hyperintense signal changes in bilateral putamina, subcortical white matter and peri-central sulcus white matter

Figure 2:DWI images showing areas of diffusion restriction involving medulla, dorsal pons, cerebellar peduncles, cerebellar vermis and dentate nuclei, midbrain, bilateral putamina and white matter adjacent to central sulci and splenium of corpus callosum.

L2-Hydroxy glutaric aciduria

L2-Hydroxy glutaric aciduria: An under recognized, slowly progressive

leucoencephalopathy of metabolic etiology

Lokesh Lingappa, Ramesh Konanki
Rainbow Children’s Hospital & Perinatal Centre, Hyderabad.

A 12-year old girl presented with initial motor delay, mild intellectual disability and seizures associated with fever. She had mild gait ataxia and incoordination, normal head size and fundus. MRI images are given here. Urine organic acids showed elevated L-2-hydroxyglutaric acid.

L2-OH glutaric aciduria is a neurometabolic disorder caused by deficiency of an FAD-linked, membrane-bound mitochondrial enzyme, L-2-hydroxyglutarate dehydrogenase. It commonly presents as mild developmental delay (motor and cognitive) that is either very slowly progressive or non-progressive, sometimes as static encephalopathy. In late childhood or adolescence, a slowly progressive neurological deterioration may be noted in the form of pyramidal, extrapyramidal, and cerebellar signs, and intellectual decline. Some children may present as learning disability in school age for the first time. These children may have seizures triggered by fever. This diagnosis should be suspected in children with relative megalencephaly, intellectual disability, mild gait disturbances, normal eyes, no evidence of peripheral neuropathy or organomegaly with no identifiable cause. MRI demonstrating leukoencephalopathy with predominant subcortical white matter involvement along with characterstic garland appearance of signal changes in the cerebellum (dentate nuclei involvement) and signal changes in bilateral globus pallidus one needs to suspect L2 hydroxy glutaric aciduria. The radiological differential diagnoses include Canavan disease and Kearns-Sayre syndrome, both of which almost always show brain stem involvement. The Urine organic acids by GCMS confirmed the diagnosis in the four of our cases with these classical MRI findings.

Figure: Axial T2 weighted MRI showing hyperintense signal changes involving bilateral dentate nuclei (A); and bilateral globi pallid, bilateral symmetric hemispheric white matter predominantly subcortical regions, more in frontoparietal lobes, sparing corpus callosum and internal caps