Peculiar aetiology for orbital apex syndrome: Wyburn-Mason syndrome as orbital apex lesion.

Background: Wyburn-Mason syndrome is a rare, non-hereditary congenital disease, belonging to the group of neurocutaneous syndromes with fewer than 100 cases reported since its first description in 1937. Case report: A young adult man was initially evaluated at the age of 2 years for proptosis and progressive visual impairment of the right eye, followed by impairment in ocular abduction, adduction and elevation as well as amaurosis. MRI revealed an expansive formation centred in the right orbit compromising conal spaces with distortion of eye muscles and optic nerve. The lesion extended through the superior orbital fissure into the right cavernous sinus and to the contralateral orbit. Despite embolisation, proptosis and oedema of the periorbital tissue continued to worsen. The combination of facial, ocular and intracranial vascular malformations and the exclusion of alternative aetiologies led to a diagnosis of cerebrofacial arteriovenous metameric syndrome (CAMS) 1 (Wyburn-Mason syndrome). Discussion: Important differential diagnoses are other CAMS, such as Sturge-Weber syndrome, as well as other conditions such as retinal cavernous haemangioma and vasoproliferative tumours. The optimal treatment regimen for severe cases of this syndrome is still unclear. Wyburn-Mason syndrome should be considered in patients presenting multiple arteriovenous malformations with orbital apex lesions.

Marked neuropsychiatric involvement and dysmorphic features in nemaline myopathy.

BACKGROUND: Inherited nemaline myopathy is one of the most common congenital myopathies. This genetically heterogeneous disease is defined by the presence of nemaline bodies in muscle biopsy. The phenotypic spectrum is wide and cognitive involvement has been reported, although not extensively evaluated. METHODS: We report two nemaline myopathy patients presenting pronounced central nervous system involvement leading to functional compromise and novel facial and skeletal dysmorphic findings, possibly expanding the disease phenotype. RESULTS: One patient had two likely pathogenic NEB variants, c.2943G > A and c.8889 + 1G > A, and presented cognitive impairment and dysmorphic features, and the other had one pathogenic variant in ACTA1, c.169G > C (p.Gly57Arg), presenting autism spectrum disorder and corpus callosum atrophy. Both patients had severe cognitive involvement despite milder motor dysfunction. CONCLUSION: We raise the need for further studies regarding the role of thin filament proteins in the central nervous system and for a systematic cognitive assessment of congenital myopathy patients.

New observations on minifascicular neuropathy with sex-dependent gonadal dysgenesis: a case series with nerve ultrasound assessment.

BACKGROUND: Gonadal dysgenesis with minifascicular neuropathy (GDMN) is a rare autosomal recessive condition associated with biallelic DHH pathogenic variants. In 46, XY individuals, this disorder is characterized by an association of minifascicular neuropathy (MFN) and gonadal dysgenesis, while in 46, XX subjects only the neuropathic phenotype is present. Very few patients with GDMN have been reported so far. We describe four patients with MFN due to a novel DHH likely pathogenic homozygous variant and the results of nerve ultrasound assessment. METHODS: This retrospective observational study included 4 individuals from 2 unrelated Brazilian families evaluated for severe peripheral neuropathy. Genetic diagnosis was performed with a peripheral neuropathy next-generation sequencing (NGS) panel based on whole exome sequencing focused analysis that included a control SRY probe to confirm genetic sex. Clinical characterization, nerve conduction velocity studies, and high-resolution ultrasound nerve evaluation were performed in all subjects. RESULTS: Molecular analysis disclosed in all subjects the homozygous DHH variant p.(Leu335Pro). Patients had a striking phenotype, with marked trophic changes of extremities, sensory ataxia, and distal anesthesia due to a sensory-motor demyelinating polyneuropathy. One 46, XY phenotypically female individual had gonadal dysgenesis. High-resolution nerve ultrasound showed typical minifascicular formation and increased nerve area in at least one of the nerves assessed in all patients. CONCLUSION: Gonadal dysgenesis with minifascicular neuropathy is a severe autosomal recessive neuropathy characterized by trophic alterations in limbs, sensory ataxia, and distal anesthesia. Nerve ultrasound studies are very suggestive of this condition and may help to avoid invasive nerve biopsies.

Moyamoya associated with Turner syndrome in a patient with type 2 spinocerebellar ataxia-Occam's razor or Hickam's dictum: a case report.

BACKGROUND: Turner syndrome (TS) is a rare condition associated with a completely or partially missing X chromosome that affects 1 in 2500 girls. TS increases the risk of autoimmune diseases, including Graves' disease (GD). Moyamoya disease is a rare cerebral arteriopathy of unknown etiology characterized by progressive bilateral stenosis of the internal carotid artery and its branches. Both TS and GD have been associated with Moyamoya. Type 2 spinocerebellar ataxia (SCA2) is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in ATXN2. We present the first case of Moyamoya syndrome in a patient with a previous diagnosis of TS and GD who tested positive for SCA2 and had imaging findings compatible with an overlap of SCA2 and Moyamoya. CASE PRESENTATION: A 43-year-old woman presented with mild gait imbalance for 2 years. Her family history was positive for type 2 spinocerebellar ataxia (SCA2). She had been diagnosed with Turner Syndrome (45,X) and Graves disease three years before. Brain MRI revealed bilateral frontal and parietal cystic encephalomalacia in watershed zones, atrophy of pons, middle cerebellar peduncles and cerebellum. MR angiography showed progressive stenosis of both internal carotid arteries with lenticulostriate collaterals, suggestive of Moya-Moya disease. Molecular analysis confirmed the diagnosis of SCA2. CONCLUSIONS: With increased availability of tools for genetic diagnosis, physicians need to be aware of the possibility of a single patient presenting two or more rare diseases. This report underscores the modern dilemmas created by increasingly accurate imaging techniques and available and extensive genetic testing.

Diagnostic approach in a patient with Creutzfeldt-Jakob disease / Abordagem diagnóstica em uma paciente com doença de Creutzfeldt-Jakob

ABSTRACT Prion diseases are an important cause of rapidly progressive dementias. Among them, the most common is sporadic Creutzfeldt-Jakob disease (CJD). It is a rare and incurable disease, with rapid progression to death. Objective: To describe the diagnostic approach of a patient with Creutzfeldt-Jakob disease. Methods: The diagnosis is established through the clinical picture associated with characteristic changes in the brain magnetic resonance imaging, the electroencephalogram, and analysis of specific changes in the cerebrospinal fluid. Results: The present report describes the case of a 53-year-old patient in the city of Fortaleza-CE. The diagnosis was made based on the clinical condition and through diagnostic tests, including 14-3-3 protein and RT QUIC analysis. Differential diagnosis was performed with other rapidly progressive causes, such as infectious and immune-mediated diseases. Conclusions: The diagnosis of probable sporadic CJD was established.

RESUMO As doenças priônicas são uma importante causa de demências rapidamente progressivas. Entre elas, a mais comum é a doença de Creutzfeldt-Jakob (DCJ) esporádica. É uma enfermidade rara e incurável, com rápida progressão para óbito. Objetivo: Descrever a abordagem diagnóstica de uma paciente com doença de Creutzfeldt-Jakob. Métodos: O diagnóstico é estabelecido pelo quadro clínico associado a alterações características na ressonância magnética cerebral, no eletroencefalograma e pela análise de alterações específicas no líquido cefalorraquidiano. Resultados: O presente relato descreve o caso de um paciente de 53 anos na cidade de Fortaleza (CE). O diagnóstico foi feito com base na condição clínica e por meio de testes diagnósticos, incluindo proteína 14-3-3 e análise Real-Time Quaking-Induced Conversion (RT QUIC). O diagnóstico diferencial foi realizado com outras causas rapidamente progressivas, como doenças infecciosas e imunomediadas. Conclusões: Por fim, foi estabelecido o diagnóstico de provável DCJ esporádica.

Characteristics and management of Susac syndrome in an emergent country: a multi-center case series from Brazil.

BACKGROUND: Susac syndrome (SS) is a rare endotheliopathy with an estimated prevalence of 0.14-0.024 per 100,000. It is an important differential diagnosis in demyelinating disorders. There are few case series and no large randomized controlled trials, and most reports come from developed countries. We report six cases of SS in three centers in Brazil and discuss management challenges in emergent countries. METHODS: This is a retrospective case series of patients diagnosed with SS in three medical centers in Brazil between April 2018 and July 2021. The European Susac consortium (EuSaC) criteria were used for diagnosis of SS. Demographic data and clinical interventions were described and outcomes were assessed subjectively and by applying the modified Rankin Scale (mRS) on last follow-up. RESULTS: Six patients were diagnosed with SS (3 males, 3 females). Mean age at presentation was 36 years (range 17 to 54). The most common initial symptom was confusion, followed by visual impairment and hearing loss. Characteristic snowball lesions on magnetic resonance imaging (MRI) were present in four patients (66%). Retinal artery abnormalities were present in half (3/6) of patients, and sensorineural hearing loss was present in four patients (66%). Outcome was favorable (mRS ≤ 2) in five patients (86%). Patients treated early had a more favorable outcome. CONCLUSION: Emergent countries face challenges in the diagnosis and management of patients with SS, such as access to advanced tests (fluorescein angiography, serial MRI) and treatment drugs (rituximab, mycophenolate). Further research should consider particularities of patients with SS in emergent countries.

Diagnostic approach in a patient with Creutzfeldt-Jakob disease.

Prion diseases are an important cause of rapidly progressive dementias. Among them, the most common is sporadic Creutzfeldt-Jakob disease (CJD). It is a rare and incurable disease, with rapid progression to death. Objective: To describe the diagnostic approach of a patient with Creutzfeldt-Jakob disease. Methods: The diagnosis is established through the clinical picture associated with characteristic changes in the brain magnetic resonance imaging, the electroencephalogram, and analysis of specific changes in the cerebrospinal fluid. Results: The present report describes the case of a 53-year-old patient in the city of Fortaleza-CE. The diagnosis was made based on the clinical condition and through diagnostic tests, including 14-3-3 protein and RT QUIC analysis. Differential diagnosis was performed with other rapidly progressive causes, such as infectious and immune-mediated diseases. Conclusions: The diagnosis of probable sporadic CJD was established.

As doenças priônicas são uma importante causa de demências rapidamente progressivas. Entre elas, a mais comum é a doença de Creutzfeldt-Jakob (DCJ) esporádica. É uma enfermidade rara e incurável, com rápida progressão para óbito. Objetivo: Descrever a abordagem diagnóstica de uma paciente com doença de Creutzfeldt-Jakob. Métodos: O diagnóstico é estabelecido pelo quadro clínico associado a alterações características na ressonância magnética cerebral, no eletroencefalograma e pela análise de alterações específicas no líquido cefalorraquidiano. Resultados: O presente relato descreve o caso de um paciente de 53 anos na cidade de Fortaleza (CE). O diagnóstico foi feito com base na condição clínica e por meio de testes diagnósticos, incluindo proteína 14-3-3 e análise Real-Time Quaking-Induced Conversion (RT QUIC). O diagnóstico diferencial foi realizado com outras causas rapidamente progressivas, como doenças infecciosas e imunomediadas. Conclusões: Por fim, foi estabelecido o diagnóstico de provável DCJ esporádica.

Cerebrotendinous Xanthomatosis: A practice review of pathophysiology, diagnosis, and treatment.

Cerebrotendinous Xanthomatosis represents a rare and underdiagnosed inherited neurometabolic disorder due to homozygous or compound heterozygous variants involving the CYP27A1 gene. This bile acid metabolism disorder represents a key potentially treatable neurogenetic condition due to the wide spectrum of neurological presentations in which it most commonly occurs. Cerebellar ataxia, peripheral neuropathy, spastic paraparesis, epilepsy, parkinsonism, cognitive decline, intellectual disability, and neuropsychiatric disturbances represent some of the most common neurological signs observed in this condition. Despite representing key features to increase diagnostic index suspicion, multisystemic involvement does not represent an obligatory feature and can also be under evaluated during diagnostic work-up. Chenodeoxycholic acid represents a well-known successful therapy for this inherited metabolic disease, however its unavailability in several contexts, high costs and common use in patients at late stages of disease course limit more favorable neurological outcomes for most individuals. This review article aims to discuss and highlight the most recent and updated knowledge regarding clinical, pathophysiological, neuroimaging, genetic and therapeutic aspects related to Cerebrotendinous Xanthomatosis.

Stiff-Eye Syndrome-Anti-GAD Ataxia Presenting with Isolated Ophthalmoplegia: A Case Report.

Anti-GAD ataxia is one of the most common forms of immune-mediated cerebellar ataxias. Many neurological syndromes have been reported in association with anti-GAD. Ophthalmoparesis has been described in stiff person syndrome. We report a case of anti-GAD ataxia presenting initially with isolated ophthalmoplegia and showing complete resolution after immunotherapy. A 26-year-old male patient presented with ophthalmoparesis characterized by tonic upwards deviation of the right eye. In the following month, he developed progressive ataxia with anti-GAD titers of 1972 UI/mL. After treatment with methylprednisolone and immunoglobulin, there was complete resolution of symptoms and anti-GAD titers decreased. This is the first report of isolated ophthalmoparesis due to tonic eye deviation associated with anti-GAD antibodies without stiff-person syndrome. Tonic eye deviation has been reported in SPS, possibly secondary to continuous discharge in gaze holding neurons in the brainstem (similar to what occurs in spinal motor neurons). With growing evidence for ocular abnormalitites in SPS, anti-GAD associated neurological syndromes should be included in the differential diagnosis of isolated ophthalmoplegia.

Intracranial mass lesions and skin discoloration in the armpits as unusual clues to Erdheim-Chester disease: a case report.

BACKGROUND: Erdheim-Chester disease (ECD) is a non-Langerhans histiocytosis that results in multi-organ disease involving the skin, bones, lungs and kidneys. Central nervous system (CNS) involvement occurs in about 50 % of patients, and diabetes insipidus, visual disturbances, and cerebellar ataxia are the most frequent neurological signs. We report a case of Erdheim-Chester disease with central nervous system involvement in the form of enhancing intracranial mass lesions with massive edema. CASE PRESENTATION: The patient presented with vertigo, ataxia, encephalopathy and pyramidal signs. Diagnosis was suggested by xanthomatous skin lesions and a biopsy was compatible with Erdheim-Chester disease demonstrating xanthogranulomas CD68 positive (clone KP1) and CD1a and S100 negative. Testing for BRAF mutation was negative, which precluded treatment with Vemurafenib. Treatment with steroids and interferon resulted in improvement of neurological signs and regression of edema on MRI. CONCLUSIONS: The diagnosis of Erdheim-Chester disease should be considered in intracranial mass lesions. Xanthomatous skin lesions are a clue to the diagnosis.

Anatomical implications of posterior cephaloceles in the dural venous sinuses.

OBJECTIVE: To analyze the venous anatomy of the dural sinuses of patients with posterior encephaloceles, in order to formulate anatomical patterns which can ensure safer surgery. METHODS: This is a retrospective study, analyzing eight patients diagnosed with posterior encephalocele throughout 1 year. RESULTS: Eight patients with cephaloceles were evaluated in our study from January 2017 to January 2018. The most common alteration was dysgenesis of the straight sinus (n = 7), followed by venous anomalies in the encephalocele and alterations in the SSS (superior sagittal sinus) (n = 4), and the occurrence of a falcine sinus (FC) in 3 patients. CONCLUSION: Anatomical variations are frequent in patients with cephaloceles. Therefore, an understanding of them is necessary for safe and effective treatment.

Presumed Zika virus-related congenital brain malformations: the spectrum of CT and MRI findings in fetuses and newborns.

OBJECTIVE: The new epidemic of Zika virus infection raises grave concerns, especially with the increasingly-recognized link between emerging cases of microcephaly and this infectious disease. Besides small cranial dimensions, there are striking morphologic anomalies in the fetal brain. Key anomalies include cortical developmental malformations and a peculiar distribution of pathologic calcifications. These potentially indicate a new pattern of congenital central nervous system infection. METHODS: Eight women underwent fetal MRI. Four infants also underwent postnatal CT. Five of the women underwent amniocentesis. RESULTS: All neonates were born with microcephaly. On fetal MRI, ventriculomegaly, marked reduction of white matter thickness, severe sylvian fissure simplification, abnormal sulcation, and diffuse volumetric loss of cerebellar hemispheres were consistently seen. On postnatal CT, diffuse subcortical and basal ganglia calcifications were observed. The Zika virus was detected in two amniocenteses by polymerase chain reaction assays. CONCLUSION: We hope to assist the medical community in recognizing the spectrum of encephalic changes related to congenital Zika virus infection.

Presumed Zika virus-related congenital brain malformations: the spectrum of CT and MRI findings in fetuses and newborns / Malformações congênitas do encéfalo presumivelmente relacionadas ao Zika vírus: espectro de achados de RM e TC em fetos e neonatos

ABSTRACT The new epidemic of Zika virus infection raises grave concerns, especially with the increasingly-recognized link between emerging cases of microcephaly and this infectious disease. Besides small cranial dimensions, there are striking morphologic anomalies in the fetal brain. Key anomalies include cortical developmental malformations and a peculiar distribution of pathologic calcifications. These potentially indicate a new pattern of congenital central nervous system infection. Methods: Eight women underwent fetal MRI. Four infants also underwent postnatal CT. Five of the women underwent amniocentesis. Results: All neonates were born with microcephaly. On fetal MRI, ventriculomegaly, marked reduction of white matter thickness, severe sylvian fissure simplification, abnormal sulcation, and diffuse volumetric loss of cerebellar hemispheres were consistently seen. On postnatal CT, diffuse subcortical and basal ganglia calcifications were observed. The Zika virus was detected in two amniocenteses by polymerase chain reaction assays. Conclusion: We hope to assist the medical community in recognizing the spectrum of encephalic changes related to congenital Zika virus infection.

RESUMO Os novos casos epidêmicos de infecção pelo vírus Zika suscitam grande preocupação, sobretudo com o crescente reconhecimento da ligação entre casos emergentes de microcefalia e esta doença infecciosa. Além da cabeça de pequenas dimensões, existem profundas alterações morfológicas no encéfalo fetal. Anomalias mais típicas incluem malformações do desenvolvimento cortical e uma distribuição peculiar de calcificações patológicas. Estes dados potencialmente indicam um novo padrão de infecção congênita do sistema nervoso central. Métodos: Oito mulheres foram submetidas a RM fetal. Quatro crianças também realizaram TC pós-natal. Cinco mulheres foram submetidas a amniocentese. Resultados: Todos os neonatos nasceram com microcefalia. Na RM fetal, ventriculomegalia, acentuada redução da espessura da substância branca, acentuada simplificação da fissura sylviana, sulcação anormal e redução volumétrica difusa dos hemisférios cerebelares foram constantes. Na TC pós-natal, calcificações difusas subcorticais e nos núcleos da base foram observadas. O vírus Zika foi detectado por PCR em duas amniocenteses. Conclusão: Esperamos dar suporte à comunidade médica em reconhecer este padrão de imagem potencialmente específico.

Pyle disease (metaphyseal dysplasia) presenting in two adult sisters.

Pyle's disease is an extremely rare skeletal disorder characterized by a benign course and an autosomal recessive genetic pattern of inheritance. Its causal mutation is still unknown. In the medical literature, fewer than 30 cases have been described to date. We report the case of two female siblings, daughters of consanguineous parents, referred to the radiology department complaining of genu valgum. Laboratory tests showed no other relevant findings. Conventional radiography plain films revealed Erlenmeyer flask deformity in bilateral femorotibial metaphyses, metaphyseal flaring of long bones, and mild sclerosis of the skull base. The clinicoradiological dissociation, along with the characteristic imaging findings, was consistent with the diagnosis of Pyle's disease. Intervention is not required in most cases, but orthopedic treatment may be required for genu valgum or fractures. Therefore, these cases emphasize the pivotal role conventional radiography plays in the correct diagnosis of this rare entity, allowing for appropriate genetic counseling.

Fetal goiter conservatively monitored during the prenatal period associated with maternal and neonatal euthyroid status.

Congenital goiter is considered a rare occurrence, and may be related to hypothyroidism, hyperthyroidism, or euthyroidism. In this report, we describe a case of fetal goiter identified in the 34th gestational week in a 41-year-old secundigravida with normal thyroid functions. A conservative approach was followed; the fetal goiter was monitored via ultrasound, which suggested this was a case of hyperthyroidism. After the birth, tests indicated that the newborn was euthyroidic. Consequently, a more detailed study using non-invasive procedures was deemed necessary to discover the precise cause of the fetal goiter during the gestational period.

Spontaneous regression of intralobar pulmonary sequestration during the pregnancy: report of two cases through relationships between mass and fetal biometry and review of the literature.

Intralobar pulmonary sequestration is a rare bronchopulmonary malformation consisting of a non-functioning lung mass that receives its arterial blood supply from systemic circulation and that does not adequately communicate with the tracheobronchial tree through a normal bronchus. These sequestrations account for 1.1-1.8% of all lung resections. Herein we present two clinical cases with a prenatal diagnosis of pulmonary sequestration using ultrasound and magnetic resonance imaging. Pulmonary images indicated a progressive decrease in the size and echogenicity of the lung mass with fetal growth, resulting in asymptomatic neonates with normal chest radiographs. We emphasize the importance of combining imaging examinations with follow-up by a multidisciplinary team working in a center specialized in maternal-fetal medicine. For the successive monitoring of the size of the lung tissue mass, we propose the calculation of the following two biometric ratios that are not yet described in the literature: mass area/head circumference and mass volume/estimated fetal weight. The second ratio was similar in both cases, a result which suggests its potential for use in estimating the probability of the spontaneous regression of intralobar pulmonary sequestration.