Stefania Bianchi Marzoli

Magnetic resonance imaging with diffusion-weighted imaging in the evaluation of thyroid-associated orbitopathy: getting below the tip of the iceberg.

AbstractObjectivesTo compare extraocular muscles (EOMs) T2, post-contrast T1 (T1Gad) signal intensity ratios (SIRs) and normalized-apparent diffusion coefficient (n-ADC) values in patients with thyroid-associated orbitopathy (TAO) at different phases of activity and severity and correlate MRI modifications to clinical evolution during follow-up.MethodsA total of 74 TAO patients were classified as active or inactive on the basis of the clinical activity score (CAS). Severity of EOM impairment was evaluated by assigning a functional score to each rectus. T2, T1Gad SIRs and n-ADC of EOMs were compared in patients with active inflammation, those with inactive disease and 26 healthy controls, and correlated with clinical scores. MRI parameter variation was correlated with clinical modifications during follow-up.ResultsAll MRI parameters in TAO EOMs were significantly higher than in healthy subjects and correlated with muscle dysfunction and CAS. EOMs of active patients showed higher T2 and T1Gad SIRs than those with inactive disease. The T2 SIR and n-ADC of normally functioning TAO EOMs were higher than those of healthy controls. SIRs decreased in clinically improved and clinically stable EOMs after therapy.ConclusionsT2 SIR, T1Gad SIR and n-ADC are objective measures of activity and severity of EOMs in TAO patients. MRI shows clinically silent muscle involvement and modifications.Key Points• MRI and DWI measures are objective, quantitative parameters of TAO activity and severity • MRI and DWI measures significantly correlate with clinical scores in TAO patients • MRI and DWI can identify clinically silent inflammation of deep orbital structures • MRI and DWI can depict subclinical modifications during follow-up • MRI and DWI may aid clinicians in choosing the most appropriate treatment

TREATMENT OF THYROID-ASSOCIATED ORBITOPATHY WITH RITUXIMAB―A NOVEL THERAPY FOR AN OLD DISEASE: CASE REPORT AND LITERATURE REVIEW

OBJECTIVE To report the use of rituximab to treat thyroid-associated orbitopathy (TAO) in a patient with a concomitant B-cell organ-specific autoimmune disorder-the stiff person syndrome (SPS). METHODS We present a case report and a review of the related literature. RESULTS A 62-year-old man with SPS, latent autoimmune diabetes of the adult, and Graves-Basedow disease was referred to our medical center because of bilateral TAO. An ophthalmologic examination documented asymmetric bilateral NOSPECS (N = no signs or symptoms; O = only signs, no symptoms; S = soft tissue involvement; P = proptosis; E = extraocular muscle involvement; C = corneal involvement; and S = sight loss) class IV TAO (left eye>right eye) with a clinical activity score of 5 on a scale of 7. Magnetic resonance imaging of the orbits documented bilateral exophthalmos (left eye>right eye) due to retrobulbar fibroadipose infiltration, bilateral increase of extrinsic ocular muscle thickness, and enhancement of the left inferior rectus muscle on T2-weighted sequences. Because of concomitant incapacitating SPS and diet-controlled latent autoimmune diabetes of the adult, we excluded long-term corticosteroid therapy as an option and considered the use of rituximab, a mouse-human chimeric monoclonal antibody targeting the CD20 protein on pre-B and mature B lymphocytes. Rituximab was administered in accordance with the protocol for rheumatoid arthritis. During the subsequent 4 months, clinical signs and symptoms of TAO dramatically resolved (clinical activity score = 0 of 7) with a sustained improvement of the spastic paraparesis. The glutamic acid decarboxylase antibody titer remained high, and glycemic control and first-phase insulin secretion did not change. CONCLUSION Treatment of active TAO with rituximab should be considered when standard intravenous pulse glucocorticoid treatment is contraindicated or ineffective and when SPS or other organ-specific autoimmune disorders with involvement of humoral autoimmunity are present, inasmuch as more than 1 disease may benefit from the use of this chimeric monoclonal antibody.

Impact of obesity and binge eating disorder on patients with idiopathic intracranial hypertension.

Background Idiopathic intracranial hypertension (IIH) is associated with obesity, and obesity is associated with binge eating disorder (BED). The aim of this paper is to address the presence and impact of BED in patients undergoing an IIH diagnostic protocol. Methods This was a cross-sectional study. Consecutive patients suspected of IIH underwent neurological, neuro-ophthalmologic and psychological examinations, neuroimaging studies and intracranial pressure (ICP) measurements through lumbar puncture in the recumbent position. IIH diagnosis was based on International Classification of Headache Disorders, 2nd Edition criteria; BED diagnosis was based on Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria. The presence of oligoclonal bands (OCBs) in the cerebrospinal fluid was also assessed. Results Forty-five patients were enrolled: 33 were diagnosed with IIH and five of them (15%) were obese with BED. Compared to non-obese patients, those who were obese, and particularly those who were obese with BED, were more likely to have an IIH diagnosis (χ2 = 14.3; p = 0.001), ICP > 200 mmH2O (χ2 = 12.7; p = 0.002) and history of abuse or neglect (χ2 = 11.2; p = 0.004). No association with OCBs was found. Conclusions We reported for the first time the presence of BED among patients with IIH and showed that BED is associated to IIH, ICP and history of abuse or neglect.

Retinal dysfunction characterizes subtypes of dominant optic atrophy

To assess preganglionic retinal function using multifocal electroretinogram (mfERG) in patients affected by dominant optic atrophy (DOA) stratified by OPA1 gene mutation.

Retinal photoreceptor functions are compromised in patients with resistance to thyroid hormone syndrome (RTHβ)

Context In animal models, disruption of thyroid hormone (TH) receptor-β (TRβ) reduces the long/medium wavelength (L/M) and increases the short-wavelength (S) cones. Retinal photoreceptor (RP) functions are unknown in patients with resistance to TH syndrome (RTHβ) with dominant-negative TRβ mutations. Objective To investigate RP functions in RTHβ. Design, Setting, and Participants Case-control study involving 27 RTHβ patients and 31 age/sex-matched controls, conducted in two tertiary referral centers in Italy. Main Outcome Measures Color vision sensitivity assessed by Farnsworth; central macular thickness (CMT) of the outer retinal layer measured by spectral-domain optical coherence tomography; and retinal function tested by full-field electroretinogram (ERG) and S-cone ERG. Results Color sensitivity was worse in RTHβ patients than controls (P = 0.002). CMT was overlapping between the study groups but directly correlated with sex hormone-binding globuline levels in RTHβ. We found a significant reduction in amplitude of the cone (P = 0.024) and of the rod response (P = 0.006) in the ERG of RTHβ patients compared with controls. The response of the L/M cones measured by a specialized ERG test was lower in RTHβ than controls (P = 0.027), whereas no differences were found in the S-cone response. No correlations were found between TH levels, total error score, or electrophysiological results. Furthermore, no differences were found between patients with maternal or de novo/paternal inheritance. Conclusions We report, to our knowledge, the first in vivo evidence of functional defects of RP in RTHβ. These changes occur independently of endogenous TH levels or the prenatal exposure to high or normal maternal TH.

Pain in optic neuropathies

Pain occurs with optic neuropathies associated with inflammatory central nervous system diseases (MS and NMO), idiopathic intracranial hypertension and spontaneous hypotension, giant cell arteritis, immunomediated systemic diseases, compressive lesions, or infective disorders. Pain can precede the onset of visual loss in acute optic neuritis, it can be irradiated to the orbital region in giant cell arteritis and parasellar compressive optic neuropathies, or it may be located to the back of the eye with posterior scleritis. History of symptoms together with complete neuro-ophthalmological examination must guide the differential diagnosis and neuroimaging. Painful visual loss due to different pathophysiological mechanisms requires specific treatment and prognosis.

Headache frequency and symptoms of depression as predictors of disability in patients with idiopathic intracranial hypertension

Idiopathic intracranial hypertension (IIH) is characterized by raised intracranial pressure (ICP) with no established pathogenesis. The disorder is strongly associated with obesity, and most of patients are female of reproductive age. Symptoms of IIH include headaches, often chronic and with associated overuse of symptomatic medications, papilledema and eventually optic nerve atrophy, transient visual obscuration and tinnitus. However, the clinical presentation is variable, and if untreated or treated with excessive delay, IIH can lead to important visual impairment [1]. Diagnosis of IIH requires the following: (a) papilledema; (b) normal neurological examination except cranial nerve abnormalities; (C) neuroimaging study with normal brain parenchyma without hydrocephalus, mass, or structural lesion, and no abnormal meningeal enhancement or venous sinus thrombosis onMRI or MR venography; (d) normal composition of cerebrospinal fluid; (e) raised lumbar puncture opening pressure. If pressure is > 250 mmH2O in lateral decubitus, the diagnosis can formally be appointed. However, the opening ICP threshold of 250mmH2O is not universally accepted, as many cases would be missed in consideration of large diurnal ICP fluctuations. For this reason, a large trial on IIH proposed less strict criteria and proposed that diagnosis of IIH can be appointed also in those cases with ICP between 200 and 250 mmH2O when associated with compelling clinical and/or MRI findings suggestive of IIH, namely pulse-synchronous tinnitus; abducens nerve palsy; grade II papilledema; no evidence of pseudopapilledema; lateral sinus stenosis or collapse on MRV; partially empty sella with unfolded perioptic nerve CSF spaces [2]. In this observational and cross-sectional study, we enrolled, between April 2013 and November 2017, 81 patients with sign and symptoms suggestive of IIH, on occasion of their participation to an inpatient structured diagnostic program [3] . The program included neurologica l , neuroophthalmologic and psychological examinations, neuroimaging study (including brain MRI and MRI angiography of intracranial vessels), and lumbar puncture with intracranial pressure assessment in the recumbent position. Complete neuroophthalmological evaluation including standardized automated perimetry, as functional measurement of optic neuropathy, and spectral domain optical coherence tomography measurements to grade papilledema or optic nerve atrophy. Chronic headache was defined migraine or tension-type headache occurring on 15 or more days/month for more than 3 months, and both headache frequency and average pain intensity were derived from headache diaries. Patients filled in some questionnaires addressing disability (the WHODAS-12), symptoms of depression (the BDI-II). Patients were also examined with regard to the presence of binge eating disorder (BED) according to established diagnostic criteria, and the severity of obesity was addressed in terms of body mass index (BMI). To address the predictors of disability, we ran a linear regression analysis with target the WHODAS-12 total score. To select predictors, we ran correlations between WHODAS-12 and continuous variables, namely BDI-II total score, number of headaches in the previous 3 months, average pain intensity, BMI, and ICP. With regard to categorical variables, namely presence of BED, episodic headache, chronic headache, visual impairment, papilledema, and optic neuropathy, those variables that * Alberto Raggi alberto.raggi@istituto–besta.it

Which Differences in Priming Effect Between Neglect and Hemianopia? A Case Description of a Bilateral Brain-Lesioned Patient

ABSTRACT It is widely known that visuospatial neglect and hemianopia maybe superimposed. We considered the differences in implicit information processing which is effective in patients with neglect but not with hemianopia. We then hypothesize that a prime-word in the neglected field should determine a semantic activation effect but not in a blind hemifield. Moreover eye movements could provide further details. In this work we considered a patient with a bilateral with the presence of either a left visual neglect and a right homonymous hemianopia. Our results supported implicit information processing in the space affected by neglect but not by hemianopia.

MRI evidence of cerebellar and extraocular muscle atrophy differently contributing to eye movement abnormalities in SCA2 and SCA28 diseases

PURPOSE Spinocerebellar ataxias type 2 and 28 (SCA2, SCA28) are autosomal dominant disorders characterized by progressive cerebellar and oculomotor abnormalities. We aimed to investigate cerebellar, brainstem, and extraocular muscle involvement in the mitochondrial SCA28 disease compared with SCA2. METHODS We obtained orbital and brain 1.5 T-magnetic resonance images (MRI) in eight SCA28 subjects, nine SCA2, and nine age-matched healthy subjects. Automated segmentation of cerebellum and frontal lobe was performed using Freesurfer software. Manual segmentations for midbrain, pons, and extraocular muscles were performed using OsiriX. RESULTS Eye movement abnormalities in SCA2 subjects were characterized by slow horizontal saccades. Subjects with SCA28 variably presented hypometric saccades, saccadic horizontal pursuit, impaired horizontal gaze holding, and superior eyelid ptosis. Quantitative brain MRI demonstrated that cerebellar and pons volumes were significantly reduced in both SCA2 and SCA28 subjects compared with controls (P < 0.03), and in SCA2 subjects compared with SCA28 (P < 0.01). Midbrain and frontal lobe volumes were also significantly reduced in SCA2 compared to controls (P < 0.03), whereas these volumes did not differ between SCA2 and SCA28 and between SCA28 and control subjects. The extraocular muscle areas were 37% to 48% smaller in SCA28 subjects compared with controls (P < 0.002), and 14% to 36% smaller compared with SCA2 subjects (P < 0.03). Extraocular muscle areas did not differ between SCA2 and controls. CONCLUSIONS Our MRI findings support the hypothesis of different cerebellar and extraocular myopathic contributions in the eye movement abnormalities in SCA2 and SCA28 diseases. In SCA28, a myopathic defect selectively involving the extraocular muscles supports a specific impairment of mitochondrial energy metabolism.