Gastroschisis and septo-optic-pituitary dysplasia: Is there an association?

AIM: There are several case reports describing patients with both optic nerve hypoplasia/septo-optic-pituitary dysplasia (ONH/SOD) and gastroschisis (GS). Our aim was to investigate whether ONH/SOD is associated with GS. METHODS: A retrospective population-based study was undertaken using the Population Research Data Repository at the Manitoba Center for Health Policy in Manitoba, Canada to investigate if any patient with ONH/SOD also had GS. In addition, Winnipeg's Surgical Database of Outcomes and Management (WiSDOM), a hospital-based paediatric surgical database, was searched to ascertain if any of the patients with GS also have ONH/SOD. RESULTS: Cases were 124 patients with ONH/SOD diagnosed during 1990-2019. None had GS. The surgical database had 188 patients from Manitoba with GS during 1991-2019. None had ONH/SOD. CONCLUSION: There does not appear to be an association between ONH/SOD and GS in our cohorts of patients with these two disorders.

Ophthalmic and Neuroimaging Associations In Optic Nerve Hypoplasia/Septo-Optic-Pituitary Dysplasia.

BACKGROUND: Optic nerve hypoplasia (ONH) and septo-optic-pituitary dysplasia (SOD) are neurodevelopmental disorders associated with congenital visual impairment. Our aim was to investigate associations between several ophthalmic and neuroimaging features in patients with ONH/SOD. METHODS: A retrospective chart and neuroimaging review was performed in patients with ONH/SOD. Ophthalmic signs (e.g., monocular best-corrected visual acuity [BCVA], nystagmus, and strabismus) and neuroimaging data were extracted and their associations were investigated. RESULTS: There were 128 patients (70 males) with ONH/SOD who had neuroimaging. Their mean age at the end of the study was 13.2 (SD: 7.5) years. Ophthalmic data were available on 102 patients (58 males). BCVA varied from normal to no light perception. There were statistically significant associations between: (A) Reduced optic nerve or chiasm size on neuroimaging and more severely impaired BCVA and (B) laterality of the reduced optic nerve or chiasm size on neuroimaging and laterality of: (1) The eye with reduced BCVA, (2) small optic disc size, and (3) RAPD, if present (p ≤ 0.0002 each). The presence of symmetrically small optic nerves on MRI was significantly more common in patients with nystagmus than when nystagmus was absent (N = 96, 75% vs. 38.6%, p < 0.0001). The presence of neuronal migration disorders, their type and laterality were not associated with BCVA and laterality of the reduced BCVA. CONCLUSION: The functional and structural associations in ONH are consistent with the impaired visual function that results from the hypoplastic anterior visual pathways. However, these associations were not perfectly concordant making prediction of adult BCVA challenging in these patients.

James Sharpe's Contributions to Neurology and Neuro-ophthalmology: A Posthumous Tribute 10 Years On.

Dr. Sharpe was a leading eye movement researcher who had also been the editor of this journal. We wish to mark the 10th anniversary of his death by providing a sense of what he had achieved through some examples of his research.

Neuroimaging Features in Children with Optic Nerve Hypoplasia and Septo-Optic-Pituitary Dysplasia.

BACKGROUND: Optic nerve hypoplasia (ONH) and septo-optic-pituitary dysplasia (SOD) are common causes of congenital visual impairment. Our primary aim was to investigate the prevalence of abnormal neuroimaging features in patients with these disorders in Manitoba, Canada, and compare them with published reports. METHODS: A retrospective neuroimaging review was performed in patients resident in Manitoba with ONH/SOD. RESULTS: There were 128 patients (M = 70) with ONH/SOD who had neuroimaging. Their mean age (SD) at the end of the study was 13.2 (7.5) years. Males were significantly more likely to have bilateral ONH and a small optic chiasm size, while females were more likely to have a left ONH and a small left optic chiasm size on neuroimaging (p = 0.049). ONH and small optic chiasm size were seen in most patients on neuroimaging. Absent septum pellucidum was noted in 40%, small pituitary gland size in 28%, neuronal migration disorders (NMD) in 20% (>1 type and bilateral in 13 cases), corpus callosum abnormalities were present in 9%, while olfactory bulbs-tracts and olfactory sulci were absent in 8.6% of cases. Unilateral ONH was not significantly associated with other structural brain abnormalities, while NMD were significantly associated with other midline brain abnormalities including a symmetrically small optic chiasm size. CONCLUSION: The prevalence of structural neuroimaging abnormalities in our cohort with ONH/SOD was generally in the same range reported in other studies with corpus callosum abnormalities being relatively less common in our study. Bilateral NMD were relatively common among patients with NMD. The association between sex and ONH laterality requires further study.

Visual Acuity Outcomes in Children With Optic Nerve Hypoplasia and Septo-Optic-Pituitary Dysplasia.

BACKGROUND: To investigate best-corrected visual acuity (BCVA) outcomes in patients with optic nerve hypoplasia (ONH)/septo-optic-pituitary dysplasia (SOD). Our primary hypothesis was that BCVA in patients with ONH/SOD does not change significantly over time. METHODS: A chart review was undertaken in patients with a confirmed diagnosis of ONH/SOD. Demographic and clinical ophthalmologic data were extracted. Quantitative BCVA data were investigated across clinic visits after converting acuities to the logarithm of the minimum angle of resolution (logMAR). RESULTS: There were 102 patients (56 males). Median age at the end of the study was 12.7 years. Median duration of follow-up was 4.5 years. BCVA significantly worsened slightly in the most affected eyes (0.056 average increase in logMAR/year, 95% confidence interval [CI]: 0.037 to 0.075) and significantly improved mildly in the lesser or equally affected eyes (0.014 average decrease in logMAR/year, 95% CI: 0.009 to 0.019) (P < 0.0001). CONCLUSIONS: Although the overall BCVA data showed a statistically significant change with time, the actual changes were small and are of doubtful meaningful clinical significance (less than one line change on a Snellen chart). Our data suggest that ONH/SOD are nonprogressive neurodevelopmental disorders. The mild worsening of BCVA in the most affected eyes may be caused by amblyopia, whereas the small improvement in the lesser or equally affected eyes may be caused by developmental maturation. In addition, the changes in BCVA may also be due to increasing reliability of visual assessments with increasing age.

Selected Ophthalmological Features in Children with Septo-Optic Dysplasia and Optic Nerve Hypoplasia.

Septo-optic dysplasia (SOD) and optic nerve hypoplasia (ONH) cause congenital visual impairment. Their aetiology is mostly unknown. Our aim was to investigate the prevalence of selected ophthalmological features in patients with these disorders. A chart review was performed on patients with SOD/ONH. Ophthalmological data were extracted. There were 102 patients (56 males). The median age at the end of the study was 12.7 years. Best-corrected visual acuity ranged from normal to no light perception. Bilateral ONH was more common than unilateral ONH. Strabismus (85%) and to a lesser extent nystagmus (52%) were both very common in our cohort. Patients with esotropia had worse visual acuity than those who had exotropia. The presence of nystagmus was more likely in cases with bilateral ONH. Therefore, patients with SOD/ONH may have normal visual acuity. Many have strabismus, which may cause amblyopia thereby further decreasing visual acuity. Nystagmus occurs commonly and its presence typically indicates bilateral ONH.

Assessing Children with Poor Coordination Can Be Tricky - A Review on Ataxia and Ataxia Mimickers and a Study of Three Children with Severe Epilepsy.

While ataxia is a relatively common presenting feature in pediatric patients, it represents only one possible cause of uncoordinated movements. Other possible causes of uncoordinated movements include ingestion of toxic substances, musculoskeletal diseases, psychogenic disorders, extrapyramidal movement disorders, peripheral neuropathies, spasticity from any cause, and epilepsy. Therefore, primary health care providers must recognize and exclude other etiologies of uncoordinated movements before attaching the label "ataxia" to any patient presenting with poor coordination. Once the presence of ataxia is confirmed, the cause should be investigated. As ataxia may be vestibular, sensory, or cerebellar in origin, medical practitioners must evaluate the diverse symptoms and signs to effectively differentiate the various types of ataxia. Three case studies are presented to illustrate the complexity associated with the assessment of ataxia. Each case will discuss a pediatric patient who displays cerebellar ataxia as a concurrent feature of a gene-specific developmental and epileptic encephalopathy. These cases will provide an example of how ataxia may be differentiated from other causes of uncoordinated movements related to epilepsy and anti-seizure medications, namely: nonconvulsive seizures, postictal state, and medication side effects or toxicity. The assessment of poor balance can be challenging at times; however, with knowledge of the differential diagnosis of poor balance, medical practitioners will be able to confidently determine the presence of true ataxia from various ataxia mimickers, thereby allowing for timely and accurate diagnosis, and appropriate management.

Congenital Cranial Dysinnervation Disorder: An Unusual Phenotype With Multiple Cranial Neuropathies and Novel Neuroimaging Findings.

Congenital cranial dysinnervation disorders result from a maldevelopment of brainstem nuclei and/or cranial nerves. In some cases, specific genetic abnormalities have been identified. We expand the clinical phenotype of these disorders with the report of a 28-month-old girl who was initially evaluated for seizures and was found to have right sixth nerve palsy, small optic discs with reduced vision in her right eye. Her development was delayed. Brain MRI showed multiple abnormalities involving other cranial nerves, the optic chiasm and brainstem. Her developmental delay and seizure disorder suggest additional cortical involvement.

Cerebellar radiological abnormalities in children with neurofibromatosis type 1: part 2 - a neuroimaging natural history study with clinical correlations.

BACKGROUND: Focal abnormal signal intensities (FASI) on brain MRI occur commonly in patients with neurofibromatosis type 1 (NF1). The natural history of cerebellar FASI and their correlation with clinical features have not been studied comprehensively. Our aims are to describe the natural history of cerebellar FASI on repeat MRI scans and correlate the findings with the clinical features in children with NF1 and cerebellar FASI. METHOD: A retrospective review of 226 brain MRI scans and hospital charts was performed in 50 patients with cerebellar FASI, who were diagnosed with NF1 during their childhood between 1999 and 2008. RESULTS: Mean age at the end of the study period was 16.1 years. There were 27 males. Mean duration of clinical follow up was 10.1 years. Mean duration between the first and the last MRI was 6.6 years (n = 36, SD: 2.8 years). FASI were rarely confined to the cerebellum. The number of FASI was highest in early childhood and decreased significantly on subsequent MRI scans in most brain regions with the exception of the cerebrum, where a fewer number of patients with a smaller number of FASI were seen. Four patterns of change in FASI size over time were determined, none correlated with the clinical features. CONCLUSIONS: In patients with NF1, the natural history of FASI including their number, age at onset, rate of size changes, and resolution if any, varies by brain region. FASI patterns of change over time showed no clinical correlate.

Cerebellar radiological abnormalities in children with neurofibromatosis type 1: part 1 - clinical and neuroimaging findings.

BACKGROUND: Many children with neurofibromatosis type 1 (NF1) have focal abnormal signal intensities (FASI) on brain MRI, whose full clinical impact and natural history have not been studied systematically. Our aims are to describe the clinical and neuroradiological features in children with NF1 and cerebellar FASI, and report on the natural history of FASI that display atypical features such as enhancement and mass effect. METHOD: A retrospective review of the hospital charts and brain MRIs was performed on children from Manitoba diagnosed between 1999 and 2008 with NF1, who also had cerebellar FASI on MRI. RESULTS: Fifty patients (mean age: 16.1y, minimum-maximum: 6.4 - 30y, 27 M) were identified. Mean duration of follow up was 10.1y. Developmental delay, learning disabilities, tumors, and visual signs occurred commonly. Cerebellar signs were not reported. Mean age of the patients at baseline MRI was 7.8 (SD: 4.5) years. FASI occurred in several brain locations and were rarely confined to the cerebellum. FASI displayed mass effect and enhancement infrequently but were associated with malignancy only once. The number of FASI at baseline MRI was significantly less in patients with attention deficient hyperactivity disorder and more if a first degree relative had NF1 or if they had decreased visual acuity. DISCUSSION: Patients with NF1 and cerebellar FASI do not have motor or consistent non-motor (e.g. developmental delay or learning disabilities) cerebellar features. The number of FASI may correlate with some clinical features. FASI may display enhancement and mass effect but they rarely become malignant.

Neuro-ophthalmologic assessment and investigations in children and adults with cerebellar diseases.

In this chapter, we present the bedside assessment and laboratory tests that are available for the neuro-ophthalmologic evaluation of children and adults with cerebellar diseases. In the evaluation of a patient with cerebellar dysfunction, recognizing the pattern of ocular motor and / or vestibular impairment is often a key step to the correct diagnosis. The cerebellum is very important in processing a wide range of different eye movements, including angular vestibulo-ocular reflexes, otolith-ocular reflexes, fixation and gaze holding, smooth pursuit eye movements, saccadic eye movements, optokinetic response, ocular alignment, and vergence. Quantitative eye movement recording is now widely available in specialized clinics and medical practices, especially for testing the vestibulo-ocular reflexes. We describe the approach for assessing specific eye movements linked to cerebellar function, discuss appropriate eye movement laboratory tests, and summarize recent related research findings. In addition, for each laboratory test, we discuss its advantages, disadvantages, indications, and interpretations. Furthermore, we provide differential diagnoses for specific ocular motor and vestibular abnormalities such as slow saccades or impaired vestibulo-ocular reflexes.

Epidemiology of Cerebellar Diseases and Therapeutic Approaches.

Diseases involving the cerebellum occur relatively commonly in children and adults around the globe. Many factors influence their epidemiology including geography, ethnicity, consanguinity, and the methodology used to ascertain patients. In addition, reliable epidemiological data rely heavily on accurate disease classification. Continuous advances in genetic research and neuroimaging modalities have resulted in improved understanding of cerebellar diseases and have led to several revisions in their classification. Recent global epidemiological studies on ataxia reported an estimated overall prevalence rate of 26/100,000 in children, a prevalence rate of dominant hereditary cerebellar ataxia of 2.7/100,000, and a prevalence rate of recessive hereditary cerebellar ataxia of 3.3/100,000. The management of cerebellar diseases is multidisciplinary and multimodal. General supportive and symptomatic therapies should be initiated. Genetic counseling should be offered, where appropriate. Few drugs, specific motor rehabilitation programs, and noninvasive cerebellar stimulation for the treatment of ataxia have been developed and seem to show early promise, but more studies are needed to replicate and fine-tune their benefits further. Some disease-specific treatments are available. For example, acetazolamide or 4-aminopyridine for patients with episodic ataxia type 2 and vitamin E for patients with ataxia caused by vitamin E deficiency.

Eyelid Retraction in Isolated Unilateral Congenital Blepharoptosis.

Isolated unilateral congenital ptosis is encountered relatively infrequently in clinical practice. It typically consists of a unilateral droopy eyelid, weak levator palpebrae superioris muscle function, lid lag, and an absent upper lid crease with no other abnormalities on examination. We present a four-and-a-half-year-old girl with isolated and mild unilateral congenital ptosis who unexpectedly demonstrated a static upper eyelid on downgaze in conjunction with a well-formed upper lid skin crease. We attribute this uncommon sign in congenital ptosis to stiffness and presumed fibrosis of the levator muscle. Examining the function of the eyelids in all directions of gaze is important in patients with abnormalities of lid position, since additional useful information can be gleaned about the status of the levator muscle including, aberrant regeneration or fibrosis.

Recurrent Ataxia in Children and Adolescents.

BACKGROUND: Recurrent ataxia is encountered infrequently in clinical pediatric neurology practise and presents with diagnostic challenges. It is caused by several disorders. Our aims were to describe the epidemiology and clinical features in children with recurrent ataxia. MATERIALS AND METHODS: A retrospective review was undertaken in 185 children with chronic ataxia, who presented during 1991 to 2008. Several databases were searched to ensure optimum ascertainment. Patients with brain tumors or isolated disorders of the peripheral nerves or vestibular system were excluded. RESULTS: Recurrent ataxia was reported in 21 patients. Their age range was between 6 and 32.75 years (males=12). The crude period prevalence rate for the 18-year study period was 7.44/100,000. Eight patients had episodic ataxia and seven had inflammatory and metabolic disorders. In the rest the etiology was unknown. Many patients presented with ataxia, dizziness, and vertigo. The frequency and duration of the ataxic episodes varied from several per day to one every few months. Other clinical features included developmental delay and seizures. Neuroimaging in episodic ataxia was normal and abnormal in inflammatory or metabolic disorders. Acetazolamide provided symptomatic relief in patients with episodic ataxia, while steroids were beneficial in patients with an inflammatory etiology. One child with a metabolic disorder died. CONCLUSIONS: Recurrent ataxia is an uncommon presentation in children and mortality is rare. Genetic, metabolic, and inflammatory disorders should be considered in these patients. Neuroimaging is essential. Acetazolamide in selected patients provides good symptomatic relief.