Intraocular Pressure Correlates with Optic Nerve Sheath Diameter in Patients with Normal Tension Glaucoma

PURPOSE: 1. Identify differences in optic nerve sheath diameter (ONSD) as an indirect measure of intracranial pressure (ICP) in glaucoma patients and a healthy population. 2. Identify variables that may correlate with ONSD in primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) patients. METHODS: Patients with NTG (n = 46) and POAG (n = 61), and healthy controls (n = 42) underwent B-scan ultrasound measurement of ONSD by an observer masked to the patient diagnosis. Intraocular pressure (IOP) was measured in all groups, with additional central corneal thickness (CCT) and visual field defect measurements in glaucomatous patients. Only one eye per patient was selected. Kruskal-Wallis or Mann-Whitney were used to compare the different variables between the diagnostic groups. Spearman correlations were used to explore relationships among these variables. RESULTS: ONSD was not significantly different between healthy, NTG and POAG patients (6.09 ± 0.78, 6.03 ± 0.69, and 5.71 ± 0.83 respectively; p = 0.08). Visual field damage and CCT were not correlated with ONSD in either of the glaucoma groups (POAG, p = 0.31 and 0.44; NTG, p = 0.48 and 0.90 respectively). However, ONSD did correlate with IOP in NTG patients (r = 0.53, p < 0.001), while it did not in POAG patients and healthy controls (p = 0.86, p = 0.46 respectively). Patient's age did not relate to ONSD in any of the groups (p > 0.25 in all groups). CONCLUSIONS: Indirect measurements of ICP by ultrasound assessment of the ONSD may provide further insights into the retrolaminar pressure component in glaucoma. The correlation of ONSD with IOP solely in NTG patients suggests that the translaminar pressure gradient may be of particular importance in this type of glaucoma.

Hereditary Neuropathy with Liability to Pressure Palsy Presenting with Hand Drop in a Young Child

Hereditary neuropathy with liability to pressure palsy (HNPP) results from the deletion of the PMP22 gene in chromosome 17p11.2. Clinically, it presents with painless pressure palsies, typically in the 2nd and 3rd decades of life, being a rare entity in childhood. We present the case study of a six-year-old male child who presented with left hand drop that he kept for over four weeks. Electrophysiological studies suggested HNPP and genetic studies confirmed it. With this paper, we pretend to create awareness to this entity as a diagnosis to be considered in a child with painless monoparesis and to emphasize the importance of electrophysiological studies in the diagnosis.

Optic Nerve Drusen: Find the Differences

Introdução: Os drusens do disco ótico são anomalias congénitas do desenvolvimento da cabeça do nervo ótico, correspondendo a depósitos hialinos calcificados, localizados anteriormente à lâmina crivosa. O seu diagnóstico é maioritariamente acidental, em doentes normalmente assintomáticos. Material e Métodos: Os autores apresentam 5 casos clínicos de doentes com idades de apresentação compreendidas entre 6 e 12 anos, observados na Consulta de Oftalmologia Pediátrica e Estrabismo, à qual foram referenciados por diferentes motivos. Resultados: Nos casos clínicos apresentados os motivos de consulta foram diminuição da acuidade visual, estrabismo divergente, cefaleias com suspeita de papiledema e rotina. O exame oftalmológico e os meios complementares de diagnóstico realizados, nomeadamente retinografia, ecografia ocular, tomografia de coerência ótica e campos visuais, contribuíram para o diagnóstico de drusens do nervo ótico. Foram ainda encontrados erros refractivos em 4 dos casos descritos. Conclusão: Salienta-se a importância de uma história clínica e observação detalhadas para o diagnóstico diferencial e despiste de patologias oftalmológicas concomitantes, em doentes com drusens do disco ótico e seus familiares.

Miosite Orbitária

Orbital myositis is a subgroup of the nonspecific inflammatory syndrome or orbital pseudotumor and is characterized by a primary inflammation of extraocular muscles. The authors describe a 70-year-old patient with acute proptosis, ocular pain and right ophthalmoplegia, whose orbital computed tomographic scan showed enlargement of the homolateral extraocular muscles. Clinical presentation and complementary tests were compatible with the diagnosis of orbital myositis however, because of the particular aspects, which included retinal central vein occlusion, optic nerve lesion, distension of the superior ophthalmic vein and the homolateral cavernous sinus, the differential diagnosis with cavernous sinus pathology and thyroid ophthalmopathy was considered. The importance of a rapid diagnosis and treatment is stressed.

Primary Disorders of Neurotransmitter Metabolism: Experience of a Tertiary Center

Neurotransmitter diseases are a group of inherited disorders attributable to a disturbance of neurotransmitter metabolism. Biogenic amines are neurotransmitters with multiple roles including psychomotor function, hormone secretion, cardiovascular, respiratory and gastrointestinal control, sleep mechanisms, body temperature and pain. Given the multiple functions of monoamines, disorders of their metabolism comprise a wide spectrum of manifestations, with motor dysfunction being the most prominent clinical feature. Methods: Case review of 12 patients from 4 families, with primary disorders of biogenic amine metabolism. Results: Aromatic L-amino acid decarboxylase deficiency (4 patients from 2 families), and GTP-cyclohydrolase (8 patients from 2 families) were the two diseases identified. Age at first symptoms varied between 2 months and 6 years. Developmental delay was present in all cases except 2 patients with GTP cyclohydrolase deficiency. The combination of axial hypotonia and limb dystonia was also frequent. Children with aromatic L-amino acid decarboxylase deficiency exhibited temperature instability, oculogyric crisis and disturbances of sleep. The index case of one family with GTP cyclohydrolase deficiency presented with Parkinsonism (bradykinesia, rigidity and hypomimia). Analysis of neurotransmitters and their metabolites in CSF was crucial for the identification of index cases. Response to therapy was variable but in general unsatisfactory except in a family with GTP cyclohydrolase deficiency. Conclusions: These disorders should be considered in the differential diagnosis of paediatric neurodegenerative diseases, in order to allow an adequate therapeutic trial that can favor prognosis.

Analysis of Synaptic Proteins in the Cerebrospinal Fluid as a New Tool in the Study of Inborn Errors of Neurotransmission

Abstract In a few rare diseases, specialised studies in cerebrospinal fluid (CSF) are required to identify the underlying metabolic disorder. We aimed to explore the possibility of detecting key synaptic proteins in the CSF, in particular dopaminergic and gabaergic, as new procedures that could be useful for both pathophysiological and diagnostic purposes in investigation of inherited disorders of neurotransmission. Dopamine receptor type 2 (D2R), dopamine transporter (DAT) and vesicular monoamine transporter type 2 (VMAT2) were analysed in CSF samplesfrom 30 healthy controls (11 days to 17 years) by western blot analysis. Because VMAT2 was the only protein with intracellular localisation, and in order to compare results, GABA vesicular transporter, which is another intracellular protein, was also studied. Spearman’s correlation and Student’s t tests were applied to compare optical density signals between different proteins. All these synaptic proteins could be easily detected and quantified in the CSF. DAT, D2R and GABA VT expression decrease with age, particularly in the first months of life, reflecting the expected intense synaptic activity and neuronal circuitry formation. A statistically significant relationship was found between D2R and DAT expression, reinforcing the previous evidence of DAT regulation by D2R. To our knowledge, there are no previous studies on human CSF reporting a reliable analysis of these proteins. These kinds of studies could help elucidate new causes of disturbed dopaminergic and gabaergic transmission as well as understanding different responses to L-dopa in inherited disorders affecting dopamine metabolism. Moreover, this approach to synaptic activity in vivo can be extended to different groups of proteins and diseases.

Trombofilias e Contracepção

Thrombophilias, whether inherited or acquired, are a topic of increased interest in women’s health. Factors that enhance thrombus formation in the presence of thrombophilia include oral contraception, hormone replacement therapy, pregnancy and the puerperium. The risk of venous thomboembolism with hormonal contraceptive use is greater in women with underlying thrombophilias, and thrombosis usually occurs earlier than in women without defined thrombophilias. The degree of increased risk varies according to the underlying thrombophilic defect, the largest bulk of evidence referring to women with Factor V Leiden or prothrombin gene mutation. However, most instances of thrombosis occur due to a combination of inherited, acquired and environmental factors. Before starting oral contraception it is important to screen patients to identify those at increased risk of thrombosis.

Low Dose Thalidomide for Treatment of Resistant Discoid Lupus Erythematosus. A Case Report

Discoid lupus erythematosus (DLE) is a chronic, indolent, disfiguring disease that is characterized by scaly, erythematous, disk-shaped patches and plaques followed by atrophy, scarring and depigmentation. In a small number of patients, it is refractory to standard therapies. In several studies, thalidomide has been reported to be an effective treatment in those cases. The most fearful side effects are teratogenicity and neuropathy. Adequate counseling and vigilance must be given to the patients. We report a 45-year-old Portuguese woman who presented with a 20-year history of severe facial and scalp DLE confirmed by histopathology. For several years, it failed to respond to several therapies, including topical, intralesional and oral corticosteroids, hydroxychloroquine, methotrexate, azathioprine and topical tacrolimus. Thalidomide was initiated at a dosage of 50mg/day and the skin lesions had improved dramatically after three weeks with complete clinical remission. Two months later, the dose was reduced to 50mg, five days per week without disease rebound. The patient´s concomitant medications during the treatment included sunscreen, hydroxycholoroquine, enoxaparin and aspirin to prevent thromboembolic events. Pregnancy testing, routine laboratory and electrocardiography were performed at regular intervals for safety monitoring and the results were within normal limits. Only minor side effects as nausea, constipation and somnolence were noted, however, they improved with dose reduction. Our data confirm that thalidomide therapy is an alternative or adjunctive treatment for patients with severe, chronic DLE that is refractory to standard therapies. In this patient, low-dose thalidomide was an effective treatment with minimal side effects.

Septic Arthritis Presenting as Brachial Plexus Neurophaty

Bone and joint infections are rare in the neonatal period. They often present with pseudo paralysis of the affected limb due to pain and discomfort caused by movement. The existence of a concomitant neuropathy is a rare and insuffi ciently understood phenomenon with few cases described. The authors report the case of a 7-week infant, born prematurely and with Staphylococcus aureus neonatal sepsis, who presented to the emergency room with a paretic right upper limb. Osteoarticular infection complicated with brachial plexus neuropathy was considered and MRI and electromyography the confi rmed diagnosis. There was a good outcome after antibiotic treatment and functional rehabilitation.

Trombofilias Hereditárias e Adquiridas

Para além de um risco aumentado de trombose materna, a trombofilia em recentemente vindo a ser associada várias complicações obstétricas. Neste artigo é efectuada uma revisão sobre as eventuais implicações para a gravidez desta entidade.

Sulfite Oxidase Deficiency – An Unusual Late and Mild Presentation

Introduction: Sulfite oxidase deficiency (SOD) is an autosomal recessive inherited disease usually presenting in the neonatal period with severe neurological symptoms including seizures, often refractory to anticonvulsant therapy, and a rapidly progressive encephalopathy resembling neonatal hypoxic ischemia, with premature death. Most patients develop dislocated ocular lenses. Later or milder presentations of SOD are being reported with increasing frequency. These presentations include neurological regression with loss of previously acquired milestones or movement disorders. Case report: We report a four years old girl presenting with intermittent ataxia and uncoordinated limb movements. A similar episode of ataxia had occurred previously, one year before, with complete neurologic recovery and normal developmental milestones. Bilateral lens dislocation had been recently diagnosed. Cranial MRI demonstrated bilateral globus pallidus enhancement. Low homocysteine was found in plasma and SulfitestR was positive. Further investigations led to confirmation of isolated sulfite oxidase deficiency with no enzyme activity detected on skin fibroblasts culture. Discussion: This case illustrates the clinical variability of SOD and it is not only atypical but also seems to be the mildest form described so far. The association of ectopia lentis with a movement disorder, even without psychomotor regression, should prompt us to look for this diagnosis.

Familial Amyloidotic Polineuropathy and Systemic Lupus

Familial amyloidotic polineuropathy is a genetic disorder, leading to systemic amyloid deposits, manifested as sensory-motor and autonomic neuropathy. In the Portuguese classical form, the disease is evident at a young age, and causes death if no specific treatment is received. Variability in penetrance, age of onset and clinical course has been published; environmental and genetic factors are believed to contribute to this variability. The authors report a case of a 51-year-old white female, with a medical history of acquired angioedema, late-onset familial amyloidotic polineuropathy and systemic lupus erythemathosus. The authors consider that these associated diseases could modulate their expression.

Achondroplasia and Down’s Syndrome – Case Report of a Rare Association

The association of achondroplasia and Down’s syndrome is very rare and only five cases have been reported in the literature so far. These two genetic alterations have overlapping features such as short stature, developmental delay or hypotonia that complicate management and follow up. We report the case of a girl that is unique since she was born from a mother with achondroplasia and a healthy father. Achondroplasia was dominantly inherited from the mother but at birth she had features of Down’s syndrome as well, confirmed later by kariotype. We review her evolution regarding physical health, cognitive problems and adaptive behavior during her eight years of life. To our knowledge this is the first report of the combination of both disorders in which the achondroplasia was inherited and not a “de novo” mutation. We address the problems resulting from the additional burden of having two disorders, and how they can be improved, aiming to help others in the future to deal with these cases.

A Novel Autosomal Recessive GJA1 Missense Mutation Linked to Craniometaphyseal Dysplasia

Craniometaphyseal dysplasia (CMD) is a rare sclerosing skeletal disorder with progressive hyperostosis of craniofacial bones. CMD can be inherited in an autosomal dominant (AD) trait or occur after de novo mutations in the pyrophosphate transporter ANKH. Although the autosomal recessive (AR)form of CMD had been mapped to 6q21-22 the mutation has been elusive. In this study, we performed whole-exome sequencing for one subject with AR CMD and identified a novel missense mutation (c.716G>A, p.Arg239Gln) in the C-terminus of the gap junction protein alpha-1 (GJA1) coding for connexin 43 (Cx43). We confirmed this mutation in 6 individuals from 3 additional families. The homozygous mutation cosegregated only with affected family members. Connexin 43 is a major component of gap junctions in osteoblasts, osteocytes, osteoclasts and chondrocytes. Gap junctions are responsible for the diffusion of low molecular weight molecules between cells. Mutations in Cx43 cause several dominant and recessive disorders involving developmental abnormalities of bone such as dominant and recessive oculodentodigital dysplasia (ODDD; MIM #164200, 257850) and isolated syndactyly type III (MIM #186100), the characteristic digital anomaly in ODDD. However, characteristic ocular and dental features of ODDD as well as syndactyly are absent in patients with the recessive Arg239Gln Cx43 mutation. Bone remodeling mechanisms disrupted by this novel Cx43 mutation remain to be elucidated.