Case Of The Month
14 year / Female
- 2nd born of NCM with normal birth & development history.
Admitted on 22/June/2019 with complaints of :
- Severe pain in right upper limb followed by difficulty in using right hand since 5 days
- Deviation of angle of mouth towards left side since 4 days.
- Gradually developed difficulty in walking over next 2-3 days.
- There was no h/o fever, headache , vomiting, trauma, seizures etc.
- Higher mental functions: Normal
- Fundus examination: Normal But diminished visual acuity.
- Cranial N: Right 7th CN palsy UMN type, Rest-normal
- Tone: right side hypotonia, reflexes not elicitable.
- Power: 3/5 over right side (UL more affected than LL); Left: 5/5
- 14 year female with acute onset right sided hemiparesis with
ipsilateral 7th nerve palsy.
- Acute ischemic stroke affecting left motor cortex/ internal capsule
(Unlikely to be brainstem, as Facial nerve palsy was of UMN type.)
- Demyelinating lesion like ADEM
- Rarely SOL/ granuloma.
Hyperintensities in bilateral thalami (Left> Right),
Superior part of mid brain,Cerebral peduncle, Anterior temporal lobes.
Revisiting clinical differentials..
- Acute ischemic stroke affecting left motor cortex/ internal capsule:
Unlikely as no significant restriction of diffusion,lesions do not pertain to a particular vascular territory..
- Demyelinating lesion like ADEM
Asymmetric patchy areas of involvement without significant diffusion restriction suggests demyelination. Other differentials on MRI findings could be Herpes encephalitis ( bilateral temporal affection), Japanese encephalitis ( bilateral thalamic involvement) but these seemed unlikely due to clinical picture of no encephalopathy.
- SOL/ granuloma: ruled out by MRI.
- CBC/URINE ROUTINE/B12/Homocysteine levels- Normal
- CSF R/M-
- sugar- 47 mg/dl, protein 89 mg/dl, cells- 02 (L-100% ).
- CSF viral panel PCR- Negative
- VEP – Abnormal (b/l prolonged latency)
- Revised summary: Demyelinating disorder (CIS: Clinically isolated syndrome) with polyfocal involvement: Brain and Optic nerves.
- Possible diagnosis: ADEM/ NMOSD/ MOG/ First episode of MS
- MRI Spine and Serum and CSF antibody panel was planned.
- Child was started on IV Methylprednisolone.
Whole Spine Screening
Spinal cord appears mildly swollen with
patchy areas of T2
hyperintensity from C4 to D7 levels.
Serum Antibody profile
- Final diagnosis: NMOSD ( NMO Spectrum disorder)
- She showed rapid improvement with no focal deficit left after treatment with IV pulse methyl prednisolone (30 mg/kg/day) for 5 days.
- Was Discharged on tapering dose of oral steroids and advised for repeat
MRI after 3 months.
- However, they did not follow up and stopped oral steroid as she had improved completely.
Brought again on 06/ Nov/2019 with..
Complaints of –
-Recurrent nausea and vomiting – since 8 days
-Diplopia and blurred vision-since 2 days
No h/o fever, headache , trauma, seizures or focal deficit.
O/E- CNS: HF- Normal,
Cranial nerves-On looking to the left, limited adduction of right eye, along with nystagmus of abducting (left eye) suggestive of Internuclear ophthalmoplegia.
Other ocular movements and other Cranial nerves : normal.
Provisional diagnosis: Relapse in a case of NMOSD (Possible brainstem lesion)
Resolution of previous lesions, but new lesion in brainstem, area postrema
Area postrema syndrome: consists of hiccups, nausea, and/or uncontrollable vomiting for several days in connection with an area postrema attack, a bulbar region, and an emetic reflex center. This region is particularly rich in aquaporin-4, the target of anti-AQP4 responsible for NMOSDs.
- ANA/ds-DNA negative
- Started On IV methyl prednisolone (30 mg/kg/day) for 5 days
- Partial response: no vomiting but diplopia persisted.
- Was started on IV Rituximab: received two doses,
- Complete recovery in following two weeks.
- Continued on oral low dose steroids,
- Last follow up in February 2020- no relapse.
- Plan is to repeat MRI Brain and Spine, regular monitoring.
- NMO has high recurrence rate (up to 90%) and patient without long term immunosuppressive therapy have worse prognosis and high mortality rate
- Spine Screening should be done in all children with demyelinating lesion in brain.
- 8% of NMOSD can have cerebral ds onset. (90 % present with ON, myelitis)
- Serum NMO Antibody testing has good sensitivity, CSF does not increase yield of test.
- Predictors of relapse are: Female sex, long spine lesion, positive ANA, Anti Ro, Anti SS/RA, Vitamin D insufficiency, elevated CSF IgG index, etc.
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.
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.
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
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.
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.
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
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