Novel de Novo Nonsense Variants in AGO3 and KHSRP: Insights into Global Developmental Delay and Autism Spectrum Disorders through Whole Genome Analysis.

BACKGROUND Neurodevelopmental disorders (NDD) are umbrella disorders that encompass global developmental delay (GDD), intellectual disability, autism spectrum disorders, motor developmental disorders, and sleep disorders. Both GDD and autism spectrum disorder are common and yet clinically and genetically heterogeneous disorders. Despite their high prevalence and the advent of sequencing detection methods, the genomic etiology of GDD and autism spectrum disorder in most patients is largely unknown. CASE REPORT In this study, we describe a 6-year-old girl with GDD, autistic features, and structural brain abnormalities, including a moderate reduction in periventricular white matter and bilateral optic nerve hypoplasia, Chiari malformation type I with normal myelinization. A comprehensive joint whole-genome analysis (WGS) of the proband and her unaffected parents was performed. The trio-WGS analysis identified novel de novo nonsense variants AGO3: c.1324C>T (p.Gln442*) and KHSRP: c.1573C>T (p.Gln525*). These variants have not been reported in gnomAD and published literature. AGO3 and KHSRP are not currently associated with a known phenotype in the Online Mendelian Inheritance in Man (OMIM); however, they may be involved in neuronal development. CONCLUSIONS This report highlights the utility of joint WGS analysis in identifying novel de novo genomic alterations in a patient with the spectrum of phenotypes of GDD and neurodevelopmental disorders. The role of these variants and genes in GDD requires further studies.

Tibial tuberosity-tibial intercondylar midpoint distance measured on computed tomography scanner is not biased during knee rotation and could be clinically more relevant than current measurement systems.

PURPOSE: The purpose of this retrospective cross-sectional case-control study was to evaluate an alternative imaging test for lateralization of the tibial tuberosity, unbiased towards knee rotation. METHODS: On axial CT images of 129 knees, classified as cases (two or more patellar luxations) and controls (no patellar luxations), two raters gauged the standard tibial tuberosity-trochlear groove (TT-TG) distance, tibial tuberosity-femoral intercondylar midpoint (TT-FIM) distance, and new tibial tuberosity-tibial intercondylar midpoint (TT-TIM) distance singly, and knee longitudinal rotation angles (LRAs), and the presence of femoral trochlear dysplasia (FTD) jointly. RESULTS: All imaging tests intercorrelated and discriminated between stability groups. TT-TIM had the lowest values with the highest precision. Though poorly, TT-TG and TT-FIM negatively correlated with age and LRAs regarding femur, but positively with presence of FTD, whereas TT-TIM was unbiased. The accuracy of TT-TG (> 20 mm), TT-FIM (> 20 mm), and TT-TIM (> 13 mm) was good with almost perfect reproducibility. Only TT-TIM was sex-biased (p = 0.009), with > 12 mm cut-off in females and (presumably) > 14 mm in males. CONCLUSION: TT-TIM is an alternative imaging test for lateralization of the tibial tuberosity, unbiased towards knee rotation.

Reversible Peripheral Facial Nerve Palsy During Airplane Travel.

BACKGROUND: Facial baroparesis is reversible palsy of the facial nerve that may occur due to a pressure change in the middle ear when ascending in an airplane or during scuba diving. The objective is to present a rare case of facial paresis during airplane travel.CASE REPORT: We report a 49-yr-old female patient who presented with a 30-min episode of transient right facial paresis with loss of taste during airplane travel. Brain magnetic resonance imaging (MRI) showed a small left parietal developmental venous anomaly, extensive inflammation of the paranasal sinuses, which were almost completely obstructed with thickened mucosa and mastoid cell secretion bilaterally. Nasal decongestants and antibiotics were prescribed. No new neurological signs or symptoms were noticed.DISCUSSION: Reversible facial baroparesis due to the pressure change in the middle ear should be considered in cases where present medical history includes ascent/airplane takeoff or prolonged diving and should not be mistaken for transitory ischemic attack.Mikus K, Tudor KI, Pavlisa G, Petravic D. Reversible peripheral facial nerve palsy during airplane travel. Aerosp Med Hum Perform. 2020; 91(8):679-681.

Management of idiopathic normal pressure hydrocephalus (iNPH) - a retrospective study.

Background: Normal pressure hydrocephalus (NPH) is communicating hydrocephalus characterised by normal intraventricular pressures. It presents with the triad of gait impairment, cognitive decline, and urinary incontinence. The term idiopathic normal pressure hydrocephalus (iNPH) is used in cases where the etiology is unknown. The aim of this study was to assess the prevalence and management of iNPH in our institution.Method: This was a retrospective study carried out at a tertiary health care center. Retrospective case series analysis was conducted using the existing electronic medical record data (2009-2017) on patients with hydrocephalus.Results: Forty-two (6.7%) patients with iNPH were identified, mean age 71.5 ± 8.8 years, 21 male (mean age 71.5 ± 9.3 years) and 21 female (mean age 71.5 ± 8.5 years). Ataxia was recorded in 39, symptoms of dementia in 31, and urinary incontinence in 29 patients. Forty patients were treated surgically by placing a ventriculoperitoneal (VP) shunt. One of the two patients treated by endoscopic third ventriculostomy (ETV) was subsequently treated by placing a VP shunt due to clinical deterioration. Significant improvements were noticed in cognitive and urinary symptoms, in the triad symptom sum score on the Japanese NPH scale, as well as in Evans' index and callosal angle (CA) on brain MRI (p < 0.05). Significant positive correlation was found between age and gait disturbance (Spearman's rho = 49.86% p = 0.0017), age and incontinence (Spearman's rho = 35.22%, p = 0.0351), age and triad symptom sum score (Spearman's rho = 44.67%, p = 0.0056), female gender and dementia (Spearman's rho = 34.94%, p = 0.0367), and among all three variables on the Japanese NPH scale (p < 0.0001).Conclusions: Treatment of iNPH with VP shunt showed significant improvement. A properly designed study is required to address the efficacy of ETV in the treatment of iNPH.

Long-term angiographic outcome of stent-assisted coiling compared to non-assisted coiling of intracranial saccular aneurysms.

AIM: To compare angiographic result at long-term follow-up, and rates of progressive occlusion, recurrence, and retreatment of stent-assisted coiled (SAC) and non-assisted coiled (NAC) intracranial saccular aneurysms. METHODS: Retrospective evaluation of department records identified 260 patients with 283 saccular intracranial aneurysms who had long-term angiographic follow-up (more than 12 months) and were successfully treated with SAC (89 aneurysms) or NAC (194 aneurysms) at the University Hospital Center Zagreb from June 2005 to July 2012. Initial and control angiographic results in both groups were graded using Roy/Raymond scale, converted to descriptive terms, and the differences between them were evaluated for statistical significance. A multivariate analysis was performed to identify factors related to progression of aneurysm occlusion and recurrence at follow-up, and those related to aneurysm retreatment. RESULTS: There were more progressively occluded aneurysms in SAC group (38 of 89 aneurysms, 42.7%) than in NAC group (46 of 194, 23.7%) (P=0.002), but there were no significant differences in the rates of recanalization, regrowth, and stable result. Multivariate logistic regression identified the use of stent as the most important factor associated with progressive occlusion (P=0.015, odds ratio 2.22, 95% confidence interval 1.17-4.21), and large aneurysm size and posterior circulation location as most predictive of aneurysm recurrence and retreatment. CONCLUSION: The use of stent is associated with delayed occlusion of initially incompletely coiled aneurysms during follow-up, but does not reduce the rate of recurrence and retreatment compared to coiling alone. Long-term angiographic follow-up is needed for both SAC and NAC aneurysms.

Endovascular treatment of internal carotid artery pseudo-aneurysm presenting with epistaxis. A case report.

Recurrent epistaxis is a rare presentation of internal carotid artery C4/C5 segment pseudo-aneurysm rupture. We describe a case of a traumatic internal carotid artery pseudo-aneurysm with recurrent epistaxis as a leading symptom that was finally managed with endovascular treatment with stent-assisted coil placement. Clopidogrel and acetylsalicylic acid orally were introduced in the therapy for further stent thrombosis prevention and epistaxis did not recur on six-month follow-up. Endovascular treatment with stent-assisted coil placement seems to be a good method for pseudo-aneurysm treatment while keeping the lumen of the parent artery patent.

Large hemorrhagic colloid cyst in a 35-year-old male.

Colloid cysts are rare benign tumors of the third ventricle with diverse clinical presentation, which vary from incidentally found cysts to acute death. An uncommon hemorrhage in these cysts is a life threatening complication which can cause obstructive hydrocephalus with acute deterioration of the patient and sudden death. We present a case of 35-year-old man with large hemorrhagic colloid cyst of a third ventricle causing acute obstructive hydrocephalus even though magnetic resonance image with low T2 signal of the cyst suggested its clinically stable nature. Only 3 cases of in vivo diagnosed hemorrhagic colloid cysts have been reported in the literature.

Beware of "old" Horner syndrome.

PURPOSE: Chronic Horner syndrome is a rare clinical condition, the etiology of which often remains undiscovered. A patient is presented with an 8-year history of Horner syndrome who was diagnosed with multiple cervical artery dissections. CASE REPORT: A 42-year-old woman presented to our emergency department with a severe occipital headache that woke her up from sleep 3 days earlier. She had a history of headaches and recalled one in particular dating back to 2003. At that time, she sought medical attention at general practitioner's office because of the terrible headache and a noticeable disparity of her pupils. She was told that she had miosis of the right pupil. The examination conducted in 2011 revealed Horner syndrome with right miosis and ptosis. A four-vessel cerebral angiography revealed an occlusion of the right internal carotid artery. The morphology of stenosis and pseudoaneurysm of C1 segment of left internal carotid artery, as well as a pseudoaneurysm of V3/V4 junction of left vertebral artery indicated a probable dissective etiology. CONCLUSIONS: This case illustrates that Horner syndrome with a chronic presentation can be as potentially dangerous as its acute counterpart and should be judiciously investigated.

Diagnostic approach of patients with longitudinally extensive transverse myelitis.

The aim of this study is to present a diagnostic and therapeutic approach in patients with LETM. In a period between June 2008 and June 2010, all patients who fulfilled criteria for LETM were included in the study. All patients underwent a standardized protocol of investigations presented in this paper. Ten patients were included (5 male, 5 female, with the age distribution from 24 to 70 years). Four patients were diagnosed with NMO/spatially limited NMO spectrum disorder, three patients were diagnosed with spinal cord ADEM, two multiple sclerosis (MS) and one patient with copper deficiency myelopathy. Laboratory support for the diagnosis of NMO was positive NMO-IgG antibody; for the diagnosis of ADEM signs of peripheral nervous system involvement on electromyoneurography; and for the diagnosis of MS brain MRI lesions typical for MS, as well as positive oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). All cases with inflammatory myelopathy were treated either with steroids or plasma exchange and copper replacement was started in the case of copper deficiency. The mean time from the first symptom until the final diagnosis was 16.3 months (range 1 month to 7 years). As each of idiopathic inflammatory demyelinating diseases that can present with LETM have specific therapy, the postponement in making the correct diagnosis can lead to a poor recovery. In patients with LETM, a standardized diagnostic approach can result in a correct diagnosis and appropriate treatment.

Endovascular treatment of AVM-associated aneurysm of anterior inferior cerebellar artery through persistent primitive hypoglossal artery.

We present a patient with the combination of persistent primitive hypoglossal artery and the origin of left common carotid artery from the brachiocephalic trunk, who had subarachnoid haemorrhage caused by a ruptured aneurysm. The aneurysm was on distal anterior inferior cerebellar artery which was a feeder to cerebellar arterio-venous malformation.

Sporadic CJD in a patient with relaplsing-remitting multiple sclerosis on an immunomodulatory treatment.

Creutzfeld-Jacob disease (CJD) is a degenerative, invariably fatal brain disorder. Multiple sclerosis (MS) is a chronic, potentially disabling, immune-mediated inflammatory demyelinating disease of the central nervous system. Here, we report a 50-year-old woman who, two years after the diagnosis of relapsing remitting MS, developed altered consciousness, dystonic posture of the left hand and myoclonic jerks. Repeated brain MRI showed hyperintensities on T2 sequences in basal ganglia bilaterally and diffusion restriction in these areas, and, since typical EEG and CSF features were present, the diagnosis of CJD was made. To the best of our knowledge, this is the first report of a glatiramer acetate-treated MS patient who developed sporadic CJD. This combination is interesting in the light of recent data suggesting that CJD and MS may share similar mechanisms of "molecular mimicry" and autoimmunity. This case also emphasizes the importance of critically assessing every new symptom even in a patient with an established diagnosis of MS.

Coexistance of cerebral sinovenous thrombosis and Dandy Walker malformation in newborn.

Cerebral sinovenous thrombosis in neonatal period may cause neurological impairment, epilepsy, and lead to stroke. It is caused primarily by coagulopathy of numerous reasons, occasionally perinatal asphyxia, traumatic delivery and hyperhomocysteinemia. Dandy-Walker malformation is characterized by agenesis or hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle, and enlargement of the posterior fossa. Dandy-Walker malformation, variant, and mega cisterna magna represent a spectrum of developmental anomalies. Insults to developing cerebellar hemispheres and the fourth ventricle are believed to be the cause of malformation. Our patient was born from noncomplicated pregnancy, noncomplicated nontraumatic vaginal delivery at term, excellent Apgar scores, without peculiarities in clinical status. She was brest-fed by the 42nd hour of life when she had rightsided seizures during sleep that repeated for five times in next 24 hours. Brain Ultrasound (US) revealed clot in left lateral ventricle, slight dilatation of left ventricle, both sided periventricular echodensity, ischemia, slight enlargement of forth ventricle and a bit smaller cerebellum. There was no visible flow through left transverse, superior sagittal and straight sinus. Magnetic Resonance (MRI) confirmed the finding and showed thrombosis of left and right transverse venous sinuses and confluence of sinuses. Electroencephalogram (EEG) showed leftsided focal changes. The newborn was treated with phenobarbiton for 8 days and had no convulsions during that period. All coagulation parameters, homocistein, lipoproteins (a) and D-dimers were normal. There were no mutations on FV R506Q, PT 20210A, MTHFR 677C/T. No antiphospholipides were found. Heart US showed no structural anomalies. No other patology or risk factors were present at the time. Before discharge, US showed hydrocephalus. Flow in affected sinuses was visible with color Doppler. MRI showed recanalization of affected sinuses, also hydrocephalus and presentation of Dandy Walker On EEG there was borderline finding. Due to progression of hydrocephalus ventriculo-peritoneal shunt was placed. In age of 1 year EEG was slower for age but without focus. Neurological development was normal for age. The question is whether this child had intrauterine insult and inception of Dandy Walker with further postnatal progress of thrombosis and evolution to full picture of Dandy Walker with hydrocephalus OR thrombosis that led to development of hydrocephalus and Dandy Walker malformation in this child were accidental coexistance.

Fragile X-premutation tremor/ataxia syndrome (FXTAS) in a young woman: clinical, genetics, MRI and 1H-MR spectroscopy correlates.

It is generally thought that fragile X-associated tremor/ataxia syndrome (FXTAS) represents a late-onset neurodegenerative disorder occuring in male carriers of a premutation expansion (55-200 CGG repeats) in the fragile X mental retardation 1 (FMR 1) gene. However, several female patients with FXTAS have also been reported recently. Here, we describe a 23-year old woman with positive family history of mental retardation and autism who presented clinically with action tremor, ataxia, emotional disturbances and cognitive dysfunction. Magnetic resonance imaging (MRI) of the brain showed diffuse cortical atrophy, while 1H-MR spectroscopy (MRS) revealed decreased levels of N-acetylaspartate (NAA) in the cerebellum, basal ganglia, and pons. Genetic testing confirmed heterozygous FMR 1 gene premutation of 100 CGG repeats in the abnormal allele and 29 CGG repeats in the normal allele. We concluded that FXTAS may be an under-recognized disorder, particularly in women.

Symptomatic capillary telangiectasia of the pons and intracerebral developmental venous anomaly - A rare association.

Various combinations of vascular malformations of the brain in one lesion have been reported, while others seem to be very rare. In this report, the authors discuss the case of a coexistence of an capillary telangiectasia of the pons and intracerebral venous anomaly. To our knowledge, this is the first report of coexistence of a capillary telangiectasia of the pons and intracerebral venous anomaly apparted from each other. These discrete vascular malformations of the brain raise attention on possible interrelations in the pathogenesis of these entities. We report a case of pontine capillary telangiectasia and intracerebral venous anomaly in a 42-year-old woman with a right side facial palsy. Hight field magnetic resonance imaging suggested presence of a capillary telangiectasia of the pons. Another lesion in the left frontal gyrus was attributable to the venous anomaly. Along with neuroradiological findings, results of the somatosensor evoked potentials, brain stem auditory potentials, laboratory analysis including blood, cerebrospinal fluid and urine investigation are demonstrated. Awareness of the magnetic resonance imaging finding of the capillary telangiectasias and of the venous anomalies may help in defining clinical correlates of this vascular malformations, while the follow up of these malformations might help to asses risk of vascular rupture. We and others previously selects capillary telangiectasia and venous anomaly in two discrete entities. Coexistence of these malformations in the brain apparted from each other appear to be very rare and raise attention on possible interactions in their natural history and pathogenesis.

Central positioning upbeat nystagmus and vertigo due to pontine stroke.

We present a female patient with central positioning nystagmus and vertigo (c-PPV) due to a pontine stroke. To our knowledge this is the first report of central upbeat positioning nystagmus caused by pontine lacunar stroke. This report, together with those published previously, supports the existence of a crossing ventral tegmental tract in humans.

Diffusion differences between pilocytic astrocytomas and grade II ependymomas.

BACKGROUND: The aim of our study was to differentiate between cerebellar pilocytic astrocytomas and grade II ependymomas on the basis of their diffusion properties. PATIENTS AND METHODS: The study prospectively included 12 patients with pilocytic astrocytomas and 5 with ependymomas. Apparent diffusion coefficients (ADC) were compared between tumour types. RESULTS: ADC values were significantly higher in pilocytic astrocytomas than ependymomas, with almost no overlapping of the range of measured ADCs between the two tumour types. CONCLUSIONS: Significant diffusion differences between pilocytic astrocytomas and grade II ependymomas enable their preoperative distinction, in combination with conventional magnetic resonance images.