Globus pallidus & kernicterus

OBJECTIVE: Dystonia is a movement disorder defined by involuntary muscle contractions leading to abnormal postures or twisting and repetitive movements. Classically dystonia has been thought of as a disorder of the basal ganglia, but newer results in idiopathic dystonia and lesion-induced dystonia in adults point to broader motor network dysfunction spanning the basal ganglia, cerebellum, premotor cortex, sensorimotor, and frontoparietal regions. It is unclear whether a similar network is shared between different etiologies of pediatric lesion-induced dystonia...

PURPOSE: This study sought to investigate the relationship between the globus pallidus/putamen T1 weighted image (T1 WI) signal intensity ratio (G/P ratio) and the acute bilirubin encephalopathy (ABE) in neonates, and to develop a new strategy for the grading and prognosis of ABE based on the G/P ratio. METHODS: A total of 77 full-term neonates with ABE were scored according to bilirubin-induced neurological dysfunction and divided into mild, moderate, and severe groups...

Kernicterus is a serious complication of hyperbilirubinemia, caused by neuronal injury due to excessive unconjugated bilirubin (UCB) in specific brain areas. This injury induced by this accumulation in the globus pallidus can induce severe motor dysfunction. Repetitive transcranial magnetic stimulation (rTMS) has shown neuroprotective effects in various neurological diseases. This study aimed to investigate the effects of rTMS on pallidal nerve damage and motor dysfunction in a rat model of kernicterus. Rats were divided into a sham group (n = 16), a model group (bilirubin with sham rTMS; n = 16) and an rTMS group (bilirubin with rTMS; n = 16)...

BACKGROUND: Kernicterus spectrum disorder (KSD) resulting from neonatal hyperbilirubinemia remains a common cause of cerebral palsy worldwide. This 12-month prospective cohort study followed neonates with hyperbilirubinemia to determine which clinical measures best predict KSD. METHODS: The study enrolled neonates ≥35 weeks gestation with total serum bilirubin (TSB) ≥ 20 mg/dl admitted to Aminu Kano Hospital, Nigeria. Clinical measures included brain MRI, TSB, modified bilirubin-induced neurologic dysfunction (BIND-M), Barry-Albright Dystonia scale (BAD), auditory brainstem response (ABR), and the modified KSD toolkit...

BACKGROUND AND PURPOSE: Despite its rarity in Western countries, kernicterus resulting from severe neonatal hyperbilirubinemia and its associated neurologic consequences still persists. Subtle MR imaging patterns may be overlooked, leading to diagnostic and prognostic uncertainties. The study systematically analyzes MR imaging pattern over time. MATERIALS AND METHODS: A retrospective MR imaging study was conducted in Departments of Pediatric Neurology at the University Children's Hospitals in Leipzig, Germany, or Tübingen, Germany, between 2012 and 2022 in patients who presented beyond the neonatal period suspected of having chronic kernicterus...

BACKGROUND: Kernicterus in the acute phase is difficult to diagnose. It depends on a high signal on T1 at the globus pallidum and subthalamic nucleus level. Unfortunately, these areas also show a relatively high signal on T1 in neonates as an expression of early myelination. Therefore, a less myelin-dependent sequence, like SWI, may be more sensitive to detecting damage in the globus pallidum area. CASE PRESENTATION: A term baby developed jaundice on day three following an uncomplicated pregnancy and delivery...

Kernicterus is a permanent condition caused by brain damage from bilirubin toxicity. Dystonia is one of the most debilitating symptoms of kernicterus and results from damage to the globus pallidus (GP). One potential therapeutic strategy to treat dystonia in kernicterus is to replace lost GP neurons and restore basal ganglia circuits through stem cell transplantation. Toward this end, we differentiated human embryonic stem cells (hESCs) into medial ganglion eminence (MGE; the embryological origin of most of the GP neurons)-like neural precursor cells (NPCs)...

BACKGROUND: Kernicterus Spectrum Disorders (KSDs) result from hyperbilirubinemia-induced brain injury. We developed a Toolkit (KSD-TK) to predict the likelihood of KSDs. This study aims to validate the KSD-TK by comparing it to clinical diagnoses made by the Kernicterus Clinic in the Division of Neurology. METHODS: Through retrospective chart review, we completed a KSD-TK for 37 patients evaluated between 2011 and 2019 using highest bilirubin, newborn risk factors, neonatal exam, follow-up exam, auditory testing, tooth enamel, and MRI brain results...

OBJECTIVE: The aim of this study was to determine whether prophylactic darbepoetin alpha and/or topiramate administration could prevent bilirubin neurotoxicity (BNTx) in experimental model of kernicterus. MATERIALS AND METHODS: A total of 60 Wistar albino rat puppies with experimental kernicterus model were included in the study. The Kernicterus was established administering a bilirubin injection via a cisterna magna puncture 30 minutes after ip drug injection. The puppies were divided into five groups with 12 in each group as shown below: a control group, bilirubin group, darbepoetin alpha group, topiramate group and darbepoetin alpha+ topiramate group...

Kernicterus is a relatively rare consequence of hyperbilirubinemia. There is an important role for MRI imaging for this entity in the appropriate clinical context as there are distinct signal changes in the globus pallidus. A case report and image findings are presented

Characteristic magnetic resonance imaging (MRI) findings in patients with chronic kernicterus are bilateral and symmetric T2-weighted hyperintensities in the globus pallidus. We report 4 cases of infants with clinical, laboratory, and MRI findings of kernicterus in this case series. This is the first MRI report of kernicterus in Ethiopia. Awareness of the disease is raised in this report, and the role of magnetic resonance in detecting signal abnormalities associated with kernicterus in the globus pallidi is underscored...

Bilateral basal ganglia lesions are a common non-specific finding seen in many diseases. One of the differential diagnoses for it, in a child, is kernicterus occurring due to hyperbilirubinemia. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common cause of severe hyperbilirubinemia. A 1-year old child presented to the hospital with history of generalized dystonia in the previous 3 days. MRI showed evidence of symmetrical lesions in bilateral globus pallidus, which were hyperintense on T2/FLAIR and isointense on T1...

Neonatal hyperbilirubinemia targets specific brain regions and can lead to kernicterus. One of the most debilitating symptoms of kernicterus is dystonia, which results from bilirubin toxicity to the globus pallidus (GP). Stem cell transplantation into the GP to replace lost neurons and restore basal ganglia circuits function is a potential therapeutic strategy to treat dystonia in kernicterus. In this study we transplanted human medial ganglionic eminence (MGE)-like neural progenitor cells (NPCs) that we differentiated into a primarily gamma-aminobutyric acid (GABA)ergic phenotype, into the GP of non-immunosuppressed jaundiced (jj) and non-jaundiced (Nj) rats...

We examined claims made against the National Health Service (NHS) involving neonatal jaundice in order to determine whether there were lessons that could be learnt from common themes.This was a retrospective anonymised study using information from the NHS Resolution database for 2001-2011.Twenty cases (16 males) had sufficient information for analysis. Fifteen had confirmed cerebral palsy and two young children had damage to the globus pallidus without confirmed CP. In three cases, the outcome was uncertain...

OBJECTIVE: To determine risk factors of T1WI high signal intensity at globus pallidus and subthalamic nucleus (GP and STN) of neonates. METHODS: Brain MR images of 186 neonates with intact clinical files were retrospectively reviewed to identify whether there were T1WI high signal intensity at GP and STN. Among them, 15 neonates received followed-up MR imaging in 1-5 months after first MR examination. Statistic comparison of clinical features between neonates with and without T1WI high signal intensity at GP and STN were performed using univariate analyses...

IMPORTANCE: Exchange transfusion is recommended for newborns with total serum bilirubin (TSB) levels thought to place them at risk for cerebral palsy (CP). However, the excess risk for CP among these infants is unknown. OBJECTIVE: To quantify the risks for CP and CP consistent with kernicterus that are associated with high TSB levels based on the 2004 American Academy of Pediatrics exchange transfusion threshold (ETT) guidelines. DESIGN, SETTING, AND PARTICIPANTS: We enrolled 2 cohorts from a population of 525,409 infants in the Late Impact of Getting Hyperbilirubinemia or Phototherapy (LIGHT) birth cohort...

Infants with chronic bilirubin encephalopathy often demonstrate abnormal bilateral, symmetric, high-signal intensity on T2-weighted magnetic resonance imaging of the globus pallidus and subthalamic nucleus, consistent with the neuropathology of kernicterus. Early magnetic resonance imaging of at-risk infants, while frequently showing increased T1-signal in these regions, may give false-positive findings due to the presence of myelin in these structures. Advanced magnetic resonance imaging including diffusion-weighted imaging, magnetic resonance spectroscopy, and diffusion tensor imaging with tractography may shed new insights into the pathogenesis of bilirubin-induced brain injury and the neural basis of long-term disability in infants and children with chronic bilirubin encephalopathy...

OBJECTIVE: Persons with severe motor and intellectual disabilities (SMID) caused by injury to the developing brain sometimes present generalized hypertonia in a specific position with extreme muscle overactivity persisting for most of the time during wakefulness. This "persistent generalized muscle contraction" is often associated with bad humor, sleep disturbance, hyperhidrosis, wasting, elevation of serum creatine kinase levels, regular daytime use of hypnotic or sedative medication, and the necessity to maintain the neck or hip in a flexed position manually...

A severe increase in total bilirubin coincided with a decline in neurologic status to comatose in a 9 yr old spayed female mixed-breed dog being treated for immune-mediated hemolytic anemia. MRI of the brain was performed to investigate potential causes for the neurologic signs. MRI revealed bilaterally symmetrical hyperintensities within the caudate nuclei, globus pallidus, thalamus, deep cerebellar nuclei, and cortical gray matter on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, which coincided with areas of bilirubin deposition and neuronal necrosis (kernicterus) identified on necropsy examination...

Classical rate-based pathway models are invaluable for conceptualizing direct/indirect basal ganglia pathways, but cannot account for many aspects of normal and abnormal motor control. To better understand the contribution of patterned basal ganglia signaling to normal and pathological motor control, we simultaneously recorded multi-neuronal and EMG activity in normal and dystonic rats. We used the jaundiced Gunn rat model of kernicterus as our experimental model of dystonia. Stainless steel head fixtures were implanted on the skulls and EMG wires were inserted into antagonistic hip muscles in nine dystonic and nine control rats...