Unusual Facial Movements (Ictal Blinking, Oculogyric Crises, and Jaw Seizure) in Severe Liver Disease: A Case Series.

Background: Seizures are reported in about one-third of patients with severe liver disease in association with acute or chronic liver failure. The majority of the seizures are of focal type. Occasionally generalized tonic-clonic seizures are seen when there is ethanol withdrawal. Not much is known about ictal blinking (IB) in severe liver disease. IB is the rare form of seizures and was reported in severe liver disease recently from this institute. Oculogyric crisis (OGC) is rarely reported in relation to the severe liver disease. OGC was also noted first time in our intensive care unit. Methods: At the Institute of Liver and Biliary Sciences (ILBS), data on patients with IB and OGC were analyzed from October 2018 to January 2023 (52 months). All the patients had video electroencephalograph (video-EEG) recording after proper permission/consent. The patients were followed up later for the course of the illness. Results: A total of 16 (12M:4F) patients were seen. Majority 12 (75%) were IB and 3 OGC. EEG was abnormal in nine (75.0%) of IB patients. Brain imaging had nonspecific findings. The outcome was based on the severity and recovery of the underlying liver disease. Conclusions: Unusual facial movements in the form of IB and OGC are reported, which are most of the time missed. This report highlights the importance of recognition of these events and proper in time management to improve the outcome.

Role of Inferior Vena Cava (IVC) Recanalization in Patients with Back Pain, Secondary to IVC Obstruction in Budd-Chiari Syndrome.

PURPOSE: To study the prevalence of back pain in patients of Budd-Chiari syndrome (BCS) with inferior vena cava (IVC) obstruction, and to evaluate the role of IVC recanalization in resolution of back pain. METHODS: All patients with BCS and IVC obstruction who underwent IVC recanalization between January 2018 and October 2022 were included. Patients with degenerative spine disease or other identifiable causes for back pain were excluded; remaining patients were assessed for the presence of back pain. In patients with back pain, pain relief was assessed at 24 h following IVC recanalization. RESULTS: Fifty-eight patients with BCS and IVC occlusion were identified, of which six with degenerative spine diseases were excluded. Of the remaining 52 patients, 34 (65.4%) had back pain, with pain score between 3 and 9. Engorged epidural venous plexus on preprocedural imaging (p = 0.002), and degree of luminal narrowing (p = 0.021) had a significant association with back pain. Twenty-nine of thirty-four patients (85.3%) with back pain had pain relief immediately following IVC recanalization, more so in patients with engorged epidural venous plexus on preprocedural imaging (p < 0.001). CONCLUSION: Back pain is one of the under-reported symptoms of IVC obstruction in BCS. IVC recanalization by IVC angioplasty with or without stenting relieves back pain due to the decompression of engorged epidural veins.

Ictal Blinking in Hepatic Encephalopathy Pre- and Post-Liver Transplant: Report of Eight Patients.

Objective Seizures are reported in 20 to 30% of cases with chronic liver disease in association with hepatic encephalopathy. Majority of these are focal seizures. Ictal blinking is reported first time in these patients pre- and post-liver transplant. Methods From November 2018 to October 2021, retrospective data was analyzed in patients with end-stage liver disease and hepatic encephalopathy, both pre- and post-liver transplant. Results Eight patients had ictal blinking, four were pre-transplant and four post-transplant. Five patients (four after liver transplant and one pre-transplant) were seizure free, three died of liver disease and multiorgan dysfunction, and one did not follow-up. Conclusion Ictal blinking in relation to liver disease and hepatic encephalopathy is reported, often missed and requires short duration antiepileptic medications.

Chronic liver disease and hepatic encephalopathy patients with new-onset focal motor status epilepticus: Indicates herpetic encephalitis.

Seizures are not common in cases with chronic liver disease. Overall seizures have been reported in 20-30% of cases in chronic liver disease associated with hepatic encephalopathy. We report two cases of chronic liver disease patients who presented with new-onset refractory focal status epilepticus (SE). Both patients had encephalitis and seizures which responded only when acyclovir was added to the treatment with antiepileptic medication. Herpes encephalitis should be considered as a possible diagnosis in new-onset focal seizures or focal SE in patients with chronic liver disease with or without hepatic encephalopathy, pending further investigations.

Liver Transplantation Reverses Hepatic Myelopathy in 2 Children With Hepatitis A Infection.

OBJECTIVES: To report 2 children with acute hepatic myelopathy after hepatitis A infection who recovered completely after living donor liver transplantation. METHODS: All the children admitted into liver intensive care unit (LICU) from November 1st 2018 to 31st October 2019, were evaluated for the neurological features. The data was collected from the admission register of the LICU unit in children below 15 years age. Medical records of these children were reviewed and data collected. Established clinical criteria were used to categorize the various grades of hepatic encephalopathy/myelopathy. RESULTS: 37 children were seen over 1-year period between 6 months to 15 years age. There were 24 male(64.9%) and 13 females. Acute liver failure was seen in 19 (51.3%) and acute on chronic liver failure in 18 (48.7%). There were 10 cases of hepatitis A in acute liver failure group,10 of 19 cases (52.6%), while Wilson's disease and undetermined etiology group formed the chronic group. 2 cases of hepatic myelopathy were seen in acute liver failure following hepatitis A infection. Both these children underwent live liver donor transplantation and recovered completely. Further in hepatitis A group,3 children had spontaneous recovery, 4 died and 1 child was discharged with end of life care. Overall out of all 37 children with liver failure,20 (54%) were discharged, 6 (16.2%) were advised end of life care and 11 (29.8%) died. CONCLUSION: Two cases (10.5%) of reversible hepatic myelopathy were seen in acute liver failure group of 19 cases. 18 out of 37 (48.6%) children had residual neurological features at discharge time.

Role of EEG in Predicting Outcome of Hepatic Encephalopathy Patients.

Introduction: A retrospective analysis of 151 patients with hepatic encephalopathy (HE) who were admitted to the liver intensive care unit (LICU) and liver transplant intensive care unit (TICU) and underwent electroencephalographic (EEG) testing was performed. We describe a method of grading the EEGs of patients with HE and predicting their subsequent outcomes. Methods: All liver failure patients with HE who underwent routine EEG testing in the LICU or TICU between October 1, 2018 and March 31, 2019, at the Institute of Liver and Biliary Sciences (ILBS) were enrolled in this analysis. The data was analyzed using Statistical Package for the Social Sciences (SPSS). The patients were divided into four grades of HE based on established EEG criteria (HE-EEG). Results: One hundred fifty-one patients [127 Male (84%), 24 Female (16%)] with HE who underwent EEG testing were enrolled. Ages ranged from 3 to 74 years, with a mean age of 48.34 years and median interquartile range (IQR) of 49 years (38-60 years). Ninety-five patients (62.9%) had grade 1 and 2 hepatic encephalopathy, with a statistically significant, worse outcome seen in grades 3 and 4 HE patients. Seizures were seen in 30 (20.1%) of HE patients. Fifteen of 30 patients with seizures (50%) were in the ethanol and nonalcoholic steatohepatitis (NASH) groups. Forty-four of 59 (74.6%) MRIs and 35 of 60 (58.3%) CTs demonstrated some type of brain abnormality in these patients. Imaging abnormalities and the presence of seizures did not contribute to a statistically worse outcome. Conclusion: EEG has an important role in predicting the outcome and prognosis in HE. Patients with grade 3 or 4 HE-EEG, or with progressive worsening of HE-EEG grading were associated with the highest mortality rates.

A Novel Splice-Site Variant in SLC12A6 Causes Andermann Syndrome without Agenesis of the Corpus Callosum.

Andermann syndrome, otherwise known as agenesis of the corpus callosum with peripheral neuropathy (ACCPN), is an autosomal recessive motor and sensory neuropathy known to be associated with ACC and mild-to-moderate intellectual disability. We present a 7-year-old girl with infantile-onset hypotonia, mild intellectual disability, and severe motor and sensory demyelinating peripheral neuropathy. Brain magnetic resonance imaging showed intact corpus callosum. Whole exome sequencing showed a novel splice-site pathogenic variant in the SLC12A6 gene. We confirm that ACC is not a mandatory feature and suggest that the term ACCPN may be misleading.

Pyridoxine Responsive Seizures: Beyond Aldehyde Dehydrogenase 7A1.

Objective Pyridoxine responsive seizures (PDRs) are characterized by early-onset seizures and epileptic encephalopathy (neonates and infants) which respond to pyridoxine. Any type of seizures can be the first presentation of PDRs in these children. The aim of this 20-year retrospective study was to report the profile of 35 children with PDRs. Materials and Methods Neonatal and infantile seizures responding to pyridoxine were analyzed retrospectively from 1998 to 2018. Depending on the clinical features, laboratory results, and genetic study, they were divided into following four groups: (A) responders with α-aminoadipic semialdehyde dehydrogenase 7A1 ( ALDH7A1 ) mutation, (B) responders with pyridoxal phosphate homeostasis protein (PLPHP) mutation, (C) responders with none of these two known mutations, (D) and responders in combination with antiepileptic medications. Results Sixteen of 35 children had genetic mutation, 4 with ALDH7A1 mutation, and 12 with PLPHP mutation recently described. Nineteen of 35 children had no genetic positivity. Conclusion A large number of children with pyridoxine response do not have known genetic confirmation. Over time, new genes, responsible for pyridoxine dependency, may be identified or an unknown metabolic disorder may be seen in these children.

PLPHP deficiency: clinical, genetic, biochemical, and mechanistic insights.

Biallelic pathogenic variants in PLPBP (formerly called PROSC) have recently been shown to cause a novel form of vitamin B6-dependent epilepsy, the pathophysiological basis of which is poorly understood. When left untreated, the disease can progress to status epilepticus and death in infancy. Here we present 12 previously undescribed patients and six novel pathogenic variants in PLPBP. Suspected clinical diagnoses prior to identification of PLPBP variants included mitochondrial encephalopathy (two patients), folinic acid-responsive epilepsy (one patient) and a movement disorder compatible with AADC deficiency (one patient). The encoded protein, PLPHP is believed to be crucial for B6 homeostasis. We modelled the pathogenicity of the variants and developed a clinical severity scoring system. The most severe phenotypes were associated with variants leading to loss of function of PLPBP or significantly affecting protein stability/PLP-binding. To explore the pathophysiology of this disease further, we developed the first zebrafish model of PLPHP deficiency using CRISPR/Cas9. Our model recapitulates the disease, with plpbp-/- larvae showing behavioural, biochemical, and electrophysiological signs of seizure activity by 10 days post-fertilization and early death by 16 days post-fertilization. Treatment with pyridoxine significantly improved the epileptic phenotype and extended lifespan in plpbp-/- animals. Larvae had disruptions in amino acid metabolism as well as GABA and catecholamine biosynthesis, indicating impairment of PLP-dependent enzymatic activities. Using mass spectrometry, we observed significant B6 vitamer level changes in plpbp-/- zebrafish, patient fibroblasts and PLPHP-deficient HEK293 cells. Additional studies in human cells and yeast provide the first empirical evidence that PLPHP is localized in mitochondria and may play a role in mitochondrial metabolism. These models provide new insights into disease mechanisms and can serve as a platform for drug discovery.

Rituximab Treatment in Myasthaenia Gravis: Report of two paediatric cases.

Myasthaenia gravis (MG) is an auto-immune disease involving the postsynaptic receptors in the neuromuscular junction. The condition is characterised by fatigable weakness of the skeletal muscles and is uncommon in children. Acetylcholinesterase inhibitors and immune-modifying medications are usually considered the mainstay of treatment. However, these medications have to be given on a lifelong basis so that patients remain in remission; furthermore, drug-related side-effects can have a major impact on quality of life. We report two paediatric cases who were treated for MG at the Sultan Qaboos University Hospital, Muscat, Oman, in 2007 and 2008, respectively. Rituximab was eventually administered to each patient after their condition failed to improve despite several years of standard treatment with acetylcholinesterase inhibitors and immune-modifying medications. Overall, rituximab resulted in complete remission in one case and significant clinical improvement in the other case.

Segmental Spinal Muscular Atrophy Localised to the Lower Limbs: First case from Oman.

Spinal muscular atrophy (SMA) is a genetic lower motor neuron disease. It usually involves all of the skeletal muscles innervated by the anterior horn cells of the spinal cord. In rare cases, there is also localised involvement of the spinal cord. We report a 10-year-old boy who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2015 with muscle weakness restricted to the lower limbs. The presence of a homozygous deletion within the survival of motor neuron 1 gene confirmed the diagnosis of SMA. To the best of the authors' knowledge, this is the first report of an Omani patient with segmental SMA involving only the lower limbs. Treatment for this rare and relatively benign form of SMA is symptomatic and includes physiotherapy.

Longitudinal extensive transverse myelitis (LETM) in children: A twenty-year study from Oman.

OBJECTIVE: The data on children with diagnosis of idiopathic transverse myelitis (ITM) was searched to find the pattern of myelitis in Oman. METHODS: A retrospective study was carried out from January1995 to December 2014. Electronic medical records and patient medical files were seen to get the complete data of the children with ITM. This work was carried out at Sultan Qaboos University hospital, Muscat, Oman. The ethical committee of the hospital had approved the study. The diagnosis was based on the established criteria. Other causes of myelopathy were excluded. RESULTS: 19 children with idiopathic transverse myelitis were found. There were 18 out of 19 (94.6%) children with longitudinal extensive transverse myelitis (LETM). CONCLUSION: Longitudinal transverse extensive myelitis is the most common form of ITM in Oman.