Beyond the Eyes: Clinico-Radiological Correlation of Bilateral Complete Horizontal Gaze Palsy in Moebius Syndrome.

Moebius syndrome is a rare disease characterized by unilateral or bilateral facial nerve palsies with/without other cranial nerve palsy. It manifests clinically with facial muscle weakness and/or ophthalmoplegia and can be associated with other physical anomalies such as various limb deformities and orofacial malformation. Herein, we have described the clinical and radiological features of Moebius syndrome in a 9-year-old female child who presented with left-side facial palsy and bilateral complete horizontal gaze palsy.

Acute encephalitis induced Kleine-Levin syndrome with episodic vertical gaze dysfunction during hypersomnia episodes.

Kleine-Levin syndrome (KLS) is a rare, recurring sleep disorder that easily ignored. Episodic upward-gaze palsy is an uncommon manifestation observed in patients of KLS, which further complicates this disorder. Although peripheral microbial infection have been recognized as most common triggers for KLS, the underlying pathophysiology of this disorder remains unclear. We reported a unique case of KLS elicited by acute encephalitis, which was confirmed by pleocytosis of cerebrospinal fluid at the early stage. The cerebrospinal fluid returned to normal over time while the attacks continued to recur frequently. Episodic upward-gaze palsy was observed during attacks and clinical symptoms were exacerbated following a subsequent COVID-19 infection. This report presents a classic KLS case with distinctive characteristics, which should facilitate more accurate and earlier diagnosis for clinicians. Furthermore, it provides a new perspective for understanding the pathogenesis of this rare disease. CITATION: Lv H, Long X, Lv Y, Zhou J. Acute encephalitis induced Kleine-Levin syndrome with episodic vertical gaze dysfunction during hypersomnia episodes. J Clin Sleep Med. 2024;20(9):1555-1556.

Supranuclear Palsy as an Initial Presentation of the Adult-Onset Niemann-Pick Type C.

(1) Background: Niemann-Pick type C1 (NP-C1) is a lysosomal storage disorder that results in the defective trafficking of cholesterol and other cellular lipids in the endosomal-lysosomal pathway. This rare autosomal recessive disorder presents in three forms based on the age of onset. The adult form presents in patients greater than 15 years of age but is rarely seen after the age of 30. Common symptoms of the late adult-onset category of NP-C1 include progressive cognitive impairment and ataxia, with psychiatric and movement disorders presenting less frequently than in other forms of NP-C1. Dystonic movement disorders present most frequently, along with chorea, myoclonus, and parkinsonism. Herein, we present a rare case of NP-C1, diagnosed at age 35 with an initial symptom of supranuclear palsy. The goal of the presented case is to highlight the importance of the neurological examination and an inclusive differential diagnosis in patients with new-onset supranuclear palsy. (2) Methods: A single case report. (3) Results: A 46-year-old male with a past medical history of NP-C1 was admitted to the hospital for respiratory distress. He was noted to have a supranuclear gaze palsy with partially preserved voluntary saccades to the right. His mother revealed that he first had difficulty moving his eyes at the age of 34. After multiple consultations and genetic testing one year later, he was diagnosed with NP-C1. (4) Conclusions: Because NP-C1 affects many regions of the brain responsible for eye movements, neurological eye assessments can be a useful tool in diagnoses. Furthermore, eye movement abnormalities may be the initial presenting symptom of NP-C1, predisposing patients to misdiagnosis with progressive supranuclear palsy and other conditions that may mimic early-stage NP-C1. Definitive diagnosis is achieved through genetic testing. Filipin staining test was the gold standard in the past. The NP-C Suspicion Index was developed to assist in diagnoses, but its efficacy is unclear with late adult-onset NP-C1. Although no cure exists, early identification can facilitate an improved symptom management course for patients. Miglustat, a glucosylceramide synthase (GCS) inhibitor, is the approved therapy in Europe specific to NP-C1 for slowing and preventing the neurological manifestations of NP-C1. Delays between symptom onset and treatment initiation are likely to result in poorer outcomes and a progression of neurological symptoms. High doses may present tolerance concerns, especially in cases of delayed treatment and advanced neurological deficit.

Compound Heterozygous ROBO3 Mutation in Two Siblings Presenting with Horizontal Gaze Palsy without Scoliosis: Case-Based Review.

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, autosomal recessively inherited disorder characterized by a congenital absence of conjugated horizontal eye movements with progressive scoliosis developing in childhood and adolescence. HGPPS is caused by mutations of the ROBO3 gene that disrupts the midline crossing of the descending corticospinal and ascending lemniscal sensory tracts in the medulla. We present two siblings, 5-year-old and 2-year-old boys with HGPPS, from non-consanguineous parents. The older brother was brought for the evaluation of moderate psychomotor retardation. He had bilateral horizontal gaze palsy with preserved vertical gaze and convergence. Scoliosis was absent. Cranial MRI showed brainstem abnormalities, and diffusion tensor imaging showed absent decussation of cortico-spinal tracts in the medulla. Clinical diagnosis of HGPPS was confirmed by sequencing of ROBO3 gene, IVS4-1G > A (c.767-1G > A) and c.328_329delinsCCC (p.Asp110Profs*57) compound heterozygous variations were found, and segregated in parents. The younger boy was first reported at 16 months of age and had the same clinical and neuroradiological findings, unlike mild psychomotor retardation. ROBO3 gene analysis showed the same variants in his brother. Our cases show the importance of evaluating eye movements in children with neurodevelopmental abnormalities and looking for brainstem abnormalities in children with bilateral horizontal gaze palsy.

Bilateral horizontal gaze palsy as an initial presentation of a clinically isolated syndrome: A case report.

Multiple sclerosis (MS) is the most common demyelinating disease affecting the central nervous system. It has a wide range of manifestations and commonly affects the visual system. Many patients with MS report decreased vision, diplopia, nystagmus, and abnormal ocular motility. Nevertheless, bilateral horizontal gaze palsies are exceptionally rarely seen. We present the case of a 24-year-old female who came to our pediatric ophthalmology clinic complaining of bilateral horizontal gaze palsy, photophobia, and eye pain for 2 days. Although the patient had a family history of MS, there was no similar or previous complaint, with an unremarkable past medical and surgical history. During the examination, she was found to have a complete bilateral absence of horizontal saccade and pursuit, with slight limitations in vertical ones. There was no nystagmus or skew deviation, and the rest of the cranial nerves (CNs) were intact. Her ocular vital signs were normal, and her corrected visual acuity was 20/20 with full-color vision. The rest of the physical and neurological examinations were unremarkable. After referral to neurology, the magnetic resonance imaging showed multiple hyperintense lesions in deep white matter, pons, and midbrain. The correlation of imaging findings with clinical presentation confirmed the diagnosis of a clinically isolated syndrome. Extra-ocular motility (EOM) significantly improved after pulse steroid therapy and five sessions of plasma exchange, but the patient developed 35 prism diopter of acquired concomitant esotropia. She underwent a right medial rectus botulinum toxin injection which dramatically improved her condition, and became orthotropic during the last 2 months of follow-up after the injection.

Report of a Novel Homozygous Intragenic DCC Duplication and a Review of Literature of Developmental Split-Brain Syndrome aka Horizontal Gaze Palsy with Progressive Scoliosis-2 with Impaired Intellectual Development Syndrome.

Introduction: Horizontal gaze palsy with progressive scoliosis-2 (HGPPS2, MIM 617542) with impaired intellectual development aka developmental split-brain syndrome is an ultra-rare congenital disorder caused by pathogenic biallelic variants in the deleted in colorectal cancer (DCC) gene. Case Presentation: We report the clinical and genetic characterization of a Syrian patient with a HGPPS2 phenotype and review the previously published cases of HGPPS2. The genetic screening was performed using exome sequencing on Illumina platform. Genetic analysis revealed a novel DCC c.(?_1912)_(2359_?)dup, p.(Ser788Tyrfs*4) variant segregating recessively in the family. This type of variant has not been described previously in the HGPPS2 patients. To date, including the case reported here, three different homozygous pathogenic frameshift variants, one homozygous missense variant, and an intragenic duplication in the DCC gene have been reported in 8 patients with the HGPPS2 syndrome. Conclusion: The analysis of duplications and deletions in the DCC should be included in the routine genetic diagnostic evaluation of patients with suspected HGPPS2. This report expands the knowledge of phenotypic and genotypic spectrum of pathogenic variants causing HGPPS2.

Horizontal Gaze Palsy and Ipsilateral Facial Nerve Palsy in Older Patient as Initial Manifestation of Very Late-Onset Multiple Sclerosis Successfully Treated with Oral Corticosteroids: A Case Report.

Introduction: Multiple sclerosis (MS) is a demyelinating condition of the central nervous system (CNS) that primarily affects young adults. Very late-onset multiple sclerosis (VLOMS) is an uncommon form of MS, accounting for only 0.5 percent of all MS patients. Eye movement impairments such as internuclear ophthalmoplegia are common in MS, while horizontal gaze palsy is an uncommon occurrence. Case Presentation: We report a case of a patient diagnosed with VLOMS who presented with left horizontal gaze palsy and ipsilateral facial nerve palsy. Brain magnetic resonance imaging showed Dawson's fingers in the left and right periventricular white matter; multiple small, round, hyperintense lesions in the left and right cortex and juxtacortical cerebellar hemisphere; and small hyperintense lesion in the left paramedian pontine reticular formation, suggesting the diagnosis of MS. Oral corticosteroids led to complete resolution of ocular movement and ipsilateral facial nerve palsy. Conclusion: We propose that neuroimaging should be performed in ophthalmoplegia with a pattern representing CNS lesion and oral corticosteroids may be an effective alternative to high-cost intravenous corticosteroids.

One-and-a-Half Syndrome in a Case of Brainstem Bleed.

One-and-a-half syndrome (OHS) is a horizontal gaze palsy in one direction with internuclear ophthalmoplegia (INO) in the other. The only eye movement possible is the abduction of the contralateral eye with nystagmus. The usual structures affected are the medial longitudinal fasciculus and paramedian pontine reticular formation or the abducens nucleus. Most commonly, the OHS is caused by ischemia and demyelinating lesions. The other causes include infectious, neoplastic, and rarely traumatic. We report a case of a 42-year-old non-compliant hypertensive female who presented with giddiness, projectile vomiting, and right-sided hemiparesis and was found to have OHS on cranial nerve examination in the emergency department (ED). In the ED, the presence of complete horizontal gaze palsy in one direction with INO in the other direction should raise suspicion of a brainstem pathology.

A case of bilateral horizontal gaze palsy and concurrent esotropia.

Purpose: To report a unique case of bilateral horizontal pontine gaze palsy with concurrent esotropia, surgical management, and post-operative follow-up. Observations: A 39-year-old male presented with diplopia and a history of neurocysticercosis. He was found to have bilateral horizontal gaze palsy and concurrent esotropia, R > L. Classic bimedial rectus recess-resect surgery was done to include resection of the right lateral rectus muscle. Follow-up three months post-op demonstrates markedly improved diplopia. Conclusion and importance: We present a recommended therapeutic approach for the rare case of concurrent bilateral horizontal gaze palsy and esotropia, which should be further evaluated in longitudinal studies.

A New Case of Autosomal-Dominant POLR3B-Related Disorder: Widening Genotypic and Phenotypic Spectrum.

POLR3B encodes the RPC2 subunit of RNA polymerase III. Pathogenic variants are associated with biallelic hypomyelinating leukodystrophy belonging to the POLR-related disorders. Recently, the association with dominant demyelinating neuropathy, classified as Charcot-Marie-Tooth syndrome type 1I (CMT1I), has been reported as well. Here we report on an additional patient presenting with developmental delay and generalized epilepsy, followed by the onset of mild pyramidal and cerebellar signs, vertical gaze palsy and subclinical demyelinating polyneuropathy. A new heterozygous de novo missense variant, c.1297C > G, p.Arg433Gly, in POLR3B was disclosed via trio-exome sequencing. In silico analysis confirms the hypothesis on the variant pathogenicity. Our research broadens both the genotypic and phenotypic spectrum of the autosomal-dominant POLR3B-related condition.

Behind the Mask of Parkinsonism: A Case Report and Literature Review on Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative condition that typically emerges in adulthood and does not exhibit any familial inheritance pattern. PSP is characterized by gradual stiffness in the central body, an inability to move the gaze upward voluntarily, postural instability, and a decline in cognitive function linked to frontal lobe dysfunction. Clinical assessment reveals a variety of findings, and cases of PSP frequently go unnoticed or are incorrectly diagnosed as other conditions. Notably, prominent neurotransmitter-related changes in PSP involve damage to the dopaminergic nigrostriatal pathway and cholinergic impairment in multiple regions. We hereby present a case of a 71-year-old female patient whose medical journey unfolds as a perplexing riddle. Despite the collective expertise of several physicians, she found herself bearing the weight of a misdiagnosis ascribed to Parkinson's Disease (PD) erroneously. She initially presented with recurring falls due to postural instability and bradykinesia, which progressed such that she became dependent on a walking aid. A comprehensive physical examination revealed indicators consistent with PSP.

Paracentral Bitemporal Hemianopsia and Acquired Supranuclear Ocular Motor Paresis Following Cardiac Surgery.

Acquired supranuclear ocular motor paresis (ASOMP) is a rare complication following cardiac surgery, characterized by limited voluntary eye motility. The exact cause and development of ASOMP after cardiac surgery remain unclear. We report a case of ASOMP with paracentral bitemporal hemianopsia with optic atrophy after cardiac surgery, which, to our knowledge, is novel. The patient demonstrated bilateral ophthalmoplegia, with gradual improvement in voluntary smooth pursuit but persistent impairment in saccadic eye movements. Interestingly, the patient showed improved proprioceptive-driven pursuit of their own hand compared to pursuit or saccades following an examiner's hand. The visual field examination revealed a bilateral paracentral temporal hemianopic field defect. The underlying mechanisms of ASOMP and potential chiasmal ischemia in this case remain unknown. Clinicians should be aware of the possibility of ASOMP following cardiac surgery, with potential slow improvement over time.

A Rare Case Report of Eight Syndrome Secondary to Syringomyelia Associated with Type I Chiari Malformation.

Eight syndrome is defined as the combination of a unilateral conjugate gaze palsy and ipsilateral seventh cranial nerve palsy. It may occur as a result of demyelinating, vascular, infectious, or compressive lesions of the brainstem localized to the caudal pontine tegmentum. A 43-year-old woman was admitted to our clinic with complaints of headache, inability to look to the left, and weakness on the left side of her face. The complaints had begun abruptly about a month before her admission. Suboccipital decompression surgery for type I Chiari malformation had been performed 10 years earlier. Neuro-ophthalmological examination revealed left-sided horizontal gaze palsy and anisocoria. Cranial and cervical magnetic resonance images revealed cerebellar tonsillar herniation and syringomyelia, the latter of which was considered to be the cause of eight syndrome. No interventions were performed, and periodic follow-up was advised on neurosurgical consultation. Left gaze palsy and facial palsy recovered almost completely in three months, while the anisocoria persisted. Syringomyelia should be considered among the causes of horizontal gaze palsy plus ipsilateral seventh nerve palsy, termed as eight syndrome. Clinical suspicion and appropriate radiological examination can aid in the diagnosis.

Midbrain hemorrhage presenting with isolated downward gaze palsy: A case report.

Background: Diseases presenting with only downward gaze palsy are extremely rare particular in cerebral hemorrhage. Case Description: A 63-year-old man with no medical history developed a downward-dominant vertical gaze paralysis with a convergence disorder. Computed tomography and magnetic resonance imaging showed a small hemorrhage of 13 mm in diameter in the right midbrain tegmental area. The patient was conservatively treated. His symptoms showed a gradual improvement from upward gaze paralysis and convergence disorder followed by downward gaze paralysis. All symptoms disappeared in 3 weeks after the onset. The center of vertical eye movement was thought to be the rostral interstitial nucleus of medial longitudinal fasciculus (riMLF) and posterior commissure (PC). Conclusion: In this case, bilateral riMLF and PC were impaired, resulting in bilateral vertical ocular motility disorder with upward gaze paralysis. Brainstem hemorrhage rarely presents with vertical gaze palsy. Most are cerebral infarctions, and few are due to cerebral hemorrhage. This case was important for better understanding the pathophysiology of an ocular motility disorder. We also summarized the characteristics of isolated vertical gaze palsy caused by cerebral hemorrhage.

Case report: Left gaze and facial nerve palsies after ventral intermediate thalamic nucleus deep brain stimulation implantation.

Deep brain stimulation (DBS) to the ventral intermediate nucleus (VIM) of the thalamus has become a common procedure for some refractory, medication-resistant movement disorders like essential tremors. The most common adverse effects from this surgery include dysarthria and gait disturbances. This case report details a left gaze and ipsilateral facial nerve palsy following overshot cannula insertion into the pons during a VIM DBS procedure. Initial patient presentation after surgery revealed significant impairment of horizontal gaze to the left. This improved during follow-up visits and after the recession of the bilateral medial recti. When considering complications of the VIM DBS procedure, surgeons should be aware of the risks of cannula overshot given the anatomic proximity between the thalamus and brainstem. Furthermore, patients should be aware of this risk when making their surgical decision. All patients who undergo VIM DBS should be assessed for cranial nerve deficits after placement.

Spectrum of Pediatric to Early Adulthood POLR3A-Associated Movement Disorders.

Background: POLR3A pathogenic variants are associated with hypomyelination, hypodontia, hypogonadism, and movement disorders. Cases: We describe the range of movement disorders seen in six patients (four female, two male) with POLR3A variants [three novel (c.2214del, c.3775G>A, c.3905G>T) and six previously reported (c.760C>T, c.1771-7C>G, c.1909+22G>A, c.2005C>T, c.2422C>T, c.3337-11T>C)]. Patient 1 presented with a neonatal progeroid syndrome and developed parkinsonism, dystonia, ataxia, and spasticity. Patient 2 presented with infant-onset rapidly progressive chorea, and dystonia. Three patients (patients 3, 5, 6) presented predominantly with ataxia in combination with spasticity and dystonia. Patient 4 developed segmental dystonia during adolescence and ataxia in early adulthood. Four patients had vertical gaze impairment. The most common brain MRI abnormality was T2-weighted/FLAIR hyperintensity of the superior cerebellar peduncles and midbrain. Conclusion: POLR3A-related disorders exhibit significant phenotypic pleomorphism. Vertical gaze dysfunction and T2-weighted/FLAIR hyperintensity of the superior cerebellar peduncles and midbrain may be useful signs suggestive of this condition.