Franca Dicuonzo

Hereditary hemorrhagic telangiectasia: clinical features in ENG and ALK1 mutation carriers

Summary.  Background: Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized by epistaxis, mucocutaneous telangiectases and visceral arteriovenous malformations (AVMs), particularly in the brain (CAVMs), lungs (PAVMs), liver (HAVMs) and gastrointestinal tract (GI). The identification of a mutated ENG (HHT1) or ALK‐1 (HHT2) gene now enables a genotype–phenotype correlation. Objective: To determine the incidence of visceral localizations and evaluate phenotypic differences between ENG and ALK1 mutation carriers. Methods: A total of 135 consecutive adult patients were subjected to mutational screening in ENG and ALK1 genes and instrumental tests to detect AVMs, such as chest–abdomen multislice computed tomography (MDCT), brain magnetic resonance imaging and magnetic resonance angiography (MRI/MRA), upper endoscopy, were offered to all patients, independent of presence of clinical symptoms. The 122 patients with identified mutations were enrolled in the study and genotype–phenotype correlations were established. Results: PAVMs and CAVMs were significantly more frequent in HHT1 (75% vs. 44%, P < 0.0005; 20% vs. 0%, P < 0.002, respectively) and HAVMs in HHT2 (60% vs. 84%, P < 0.01). No age difference was found for PAVMs whereas HAVMs were significantly higher in older patients in both HHT1 and HHT2. Neurological manifestations secondary to CAVMs/PAVMs were found only in HHT1 patients, whereas severe liver involvement was detected only in HHT2. Respiratory symptoms were mainly detected in HHT1. Conclusions: Our study evidences a higher visceral involvement in HHT1 and HHT2 compared with previous reports. HHT1 is more frequently associated with congenital AVM malformations, such as CAVMs and PAVMs whereas HHT2 predominantly involves the liver. The ENG gene should be first targeted for mutational screening in the presence of large PAVM in patients < 45 years.

Cortical Thinning and Clinical Heterogeneity in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) has heterogeneous clinical features that could be translated into specific patterns of brain atrophy. In the current study we have evaluated the relationship between different clinical expressions of classical ALS and measurements of brain cortical thickness. Cortical thickness analysis was conducted from 3D-MRI using FreeSurfer software in 29 ALS patients and 20 healthy controls. We explored three clinical traits of the disease, subdividing the patients into two groups for each of them: the bulbar or spinal onset, the higher or lower upper motor neuron burden, the faster or slower disease progression. We used both a whole brain vertex-wise analysis and a ROI analysis on primary motor areas. ALS patients showed cortical thinning in bilateral precentral gyrus, bilateral middle frontal gyrus, right superior temporal gyrus and right occipital cortex. ALS patients with higher upper motor neuron burden showed a significant cortical thinning in the right precentral gyrus and in other frontal extra-motor areas, compared to healthy controls. ALS patients with spinal onset showed a significant cortical thinning in the right precentral gyrus and paracentral lobule, compared to healthy controls. ALS patients with faster progressive disease showed a significant cortical thinning in widespread bilateral frontal and temporal areas, including the bilateral precentral gyrus, compared to healthy controls. Focusing on the primary motor areas, the ROI analysis revealed that the mean cortical thickness values were significantly reduced in ALS patients with higher upper motor neuron burden, spinal onset and faster disease progression related to healthy controls. In conclusion, the thickness of primary motor cortex could be a useful surrogate marker of upper motor neuron involvement in ALS; also our results suggest that cortical thinning in motor and non motor areas seem to reflect the clinical heterogeneity of the disease.

Hereditary hemorrhagic telangiectasia: arteriovenous malformations in children.

OBJECTIVE To evaluate the clinical features in a large cohort of pediatric patients with genetically confirmed hereditary hemorrhagic telangiectasia (HHT) and to identify possible predictors of arteriovenous malformation (AVM) onset or clinical significance. STUDY DESIGN Prospective cross-sectional survey of all children subjected to screening for AVMs in the multidisciplinary HHT center. All patients proved to be carriers of endoglin mutations or activin A receptor type-II-like kinase 1 mutations, defined as HHT1 and HHT2, respectively. A full clinical-radiological protocol for AVM detection was adopted, independent from presence or absence of AVM-related symptoms. RESULTS Forty-four children (mean age, 10.3 years; range, 1-18) were subjected to a comprehensive clinical-radiologic evaluation. This investigation disclosed cerebrovascular malformations in 7 of 44 cases, pulmonary AVMs in 20 of 44 cases, and liver AVMs in 23 of 44 cases. Large visceral AVMs were found in 12 of 44 children and were significantly more frequent in patients with HHT1. Only large AVMs were associated with symptoms and complications. CONCLUSIONS Children with HHT have a high prevalence of AVMs; therefore, an appropriate clinical and radiological screening protocol is advisable. Large AVMs can be associated with complications in childhood, whereas small AVMs probably have no clinical risk.

Posterior Reversible Encephalopathy Syndrome Associated With Methotrexate Neurotoxicity: Conventional Magnetic Resonance and Diffusion-Weighted Imaging Findings

The addition of intrathecal methotrexate to treatment protocols has increased survival rates in children with acute lymphoblastic leukemia but is also associated with varying degrees of neurotoxicity. We describe a 15-year-old female patient diagnosed with acute lymphoblastic leukemia presenting with status epilepticus after receiving intrathecal methotrexate. Magnetic resonance imaging showed reversible cortical and subcortical changes consisting of high-intensity lesions on T2-weighted and fluid-attenuated inversion recovery sequences with postgadolinium enhancement, low signal intensity on diffusion-weighted imaging and increased apparent diffusion coefficient. These findings were consistent with the posterior reversible encephalopathy syndrome. We report our conventional magnetic resonance and diffusion-weighted imaging findings and briefly discuss the pathophysiology of the syndrome.

Imaging Studies in Partial Epilepsy in Children and Adolescents

Summary: We reviewed the results of imaging studies on 111 children and adolescents with partial epilepsy to determine which imaging procedure had the greatest sensitivity and specificity for partial epilepsy in this age range. All cases were classified as idiopathic, lesional, and cryptogenic epilepsy based on the 1989 International League Against Epilepsy Classification. All patients had magnetic resonance imaging (MRI) and 98 also had computed tomography (CT). Thirty patients with negative CT had MRI lesions that were most likely the cause of the epilepsy, and the initial diagnosis of cryptogenic partial epilepsy was changed to lesional partial epilepsy. We concluded that CT use is unwarrantedly common. MRI should be considered the procedure of first choice. CT has a complementary role, and functional neuroimaging should be encouraged.

Influence of MTHFR Genotype on Contingent Negative Variation And MRI Abnormalities in Migraine

Background.—The MTHFR C677T genotype has been associated with increased risk of migraine, particularly of migraine with aura (MA) in selected clinical samples and with elevated homocysteine. The hyper‐homocysteinemia may favor the vascular and neuronal mechanism underlying migraine, and the risk of stroke.

18 F-FDG PET/CT contribution to diagnosis and treatment response of rhino-orbital-cerebral mucormycosis

OBJECTIVE Mucormycosis is an infection caused by mycetes mucorales, emerged as a life-threatening infection associated with severe morbidity and high mortality. Conventional imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) are usually performed to assess mucormycosis extension, but they may present insufficiencies in their performance. CASE PRESENTATION We present the case of a 13 years old patient with diagnosis of rhino-orbital-cerebral mucormycosis (RCM) who performed head MRI and [(18)F]2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) both for the infection spread assessment and for the early evaluation of response to systemic amphotericin-B treatment. CONCLUSION This case suggests that (18)F-FDG PET/CT could be considered as a valuable tool for the initial staging of RCM when compared with MRI and should be performed as soon as possible after the first clinical suspicion of this disease. In addition (18)F-FDG PET/CT may also be useful for the assessment of response to treatment.

Smooth Pursuit Eye Movements among Storage Battery Workers

Eleven male workers in a battery storage plant with lead and erythrocyte protoporphyrin blood actual levels greater than 50 and 100 micrograms %, respectively, and 18 male controls without lead exposure were tested by a clinical pendular eye tracking test (PETT). Each worker underwent a series of lead absorption measurements including blood lead, urinary lead, erythrocyte protoporphyrin, delta-aminolevulinic acid dehydratase activity, and urinary delta-aminolevulinic acid. The SPEMs were evaluated by an eye tracking technique. The subjects followed a horizontally moving target which, in the form of a luminous spot on a dark background, was projected onto a screen placed 1 m from the subject. The maximum predicted eye movement velocity during tracking was about 30 degrees/s. Skin electrodes were applied on the outer canthi of both eyes and SPEM were plotted on a polygraph, recording both the actual eye movements and the corresponding first derivative. Our findings suggest that lead workers display a disorder of motor coordination of SPEMs system, and the PETT is useful, when associated with biochemical data, to evaluate the degree of subclinical damage of nervous system during lead poisoning.

Vertebral Bone Marrow Edema (vbme) in Conservatively Treated Acute Vertebral Compression Fractures (vcfs): Evolution and Clinical Correlations

Study Design. Prospective observational study. Objective. To assess (1) the evolution of vertebral bone marrow edema (VBME) in patients with A1 vertebral compression fractures (VCFs) conservatively treated and (2) the relationship between VBME and clinical symptoms, evaluated as Visual Analogue Scale (VAS) back pain and Oswestry Disability Index (ODI). Summary of Background Data. VBME is a marker of acute–subacute vertebral fractures. Little is known about the evolution of VBME in conservatively managed VCFs, as well as its clinical meaning. Methods. 82 thoracic or lumbar VCFs (21 post-traumatic; 61 osteoporotic VCFs), type A1 according to the AOSpine thoracolumbar spine injury classification system, in 80 patients were treated with C35 hyperextension brace for 3 months, bed rest for the first 25 days. Patients with osteoporotic fractures also received antiresorptive therapy and vitamin D supplementation. At 0 (T0), 30 (T1), 60 (T2), and 90 (T3) days, patients underwent magnetic resonance imaging evaluation and clinical evaluation, using VAS for pain and ODI. The paired t test was used to compare changes within groups at each follow-up versus baseline. The unpaired t test after ANOVA (analysis of variance) was used to compare the 2 groups at each follow-up. The association between VBME area, VAS score, and ODI score was analyzed by the Pearson correlation test. The tests were 2-tailed with a confidence level of 5%. Results. A significant VBME mean area, VAS, and ODI scores reduction was recorded at 60 and 90-days follow-ups versus baseline. A positive correlation between VBME reduction and clinical symptoms improvement (VAS and ODI scores improvement) was found in both traumatic and osteoporotic VCFs. Conclusion. In benign A1 VCFs conservatively managed, VBME slowly decreases in the first 3 months of magnetic resonance imaging follow-up. This VBME reduction is related to clinical symptoms improvement. Level of Evidence: 4

Ophthalmoplegic migraine: Migraine or oculomotor neuropathy?

Background Ophthalmoplegic migraine (OM) is a rare condition characterized by the association of headaches and an oculomotor nerve palsy. The third cranial nerve is commonly involved in recurrent attacks, whereas involvement of the sixth and fourth nerves is uncommon. It is still debated whether an uncontrolled migraine or an oculomotor neuropathy may be the primary cause of ophthalmoplegic migraine. Cases We report two patients affected by OM with normal magnetic resonance imaging findings and a history of uncontrolled migraine before an attack of OM. Conclusion The cases reported allow us to hypothesize that OM may be considered a form of migraine rather than a cranial neuralgia. It is possible that different factors such as inflammatory or structural factors, may represent a vulnerability of the nerve during a severe migraine attack causing ophthalmoplegia.