Andrea Elefante

Predictors of remission of hyperprolactinaemia after long‐term withdrawal of cabergoline therapy

Background  Remission rates of 76, 69·5 and 64·3% have been reported in patients with nontumoural hyperprolactinaemia (NTH), microprolactinoma and macroprolactinoma, respectively, 2–5 years after cabergoline (CAB) withdrawal.

Homozygous mutation in the prokineticin-receptor2 gene (Val274Asp) presenting as reversible Kallmann syndrome and persistent oligozoospermia: Case Report

Prokineticin 2 (Prok2) or prokineticin-receptor2 (Prok-R2) gene mutations are associated with Kallmann syndrome (KS). We describe a new homozygous mutation of Prok-R2 gene in a man displaying KS with an apparent reversal of hypogonadism. The proband, offspring of consanguineous parents, presented at age 19 years with absent puberty, no sense of smell, low testosterone and gonadotrophin levels. Magnetic resonance imaging showed olfactory bulb absence. The patient achieved virilization and spermatogenesis with gonadotrophin administration. Two years after discontinuing hormonal therapy, he maintained moderate oligozoospermia and normal testosterone levels. Prok2 and Prok-R2 gene sequence analyses were performed. The proband had a homozygous mutation in Prok-R2 exon 2 that harbours the c.T820>A base substitution, causing the introduction of an aspartic acid in place of valine at position 274 (Val274Asp). His mother had the same mutation in heterozygous state. This report describes a novel homozygous mutation of Prok-R2 gene in a man with variant KS, underlying the role of Prok-R2 gene in the olfactory and reproductive system development in humans. Present findings indicate that markedly delayed activation of gonadotrophin secretion may occur in some KS cases with definite gene defects, and that oligozoospermia might result from a variant form of reversible hypogonadotrophic hypogonadism.

Early clinical and neuroradiological worsening after radiotherapy and concomitant temozolomide in patients with glioblastoma: Tumour progression or radionecrosis?

OBJECTIVES This study investigates the diagnosis and management of patients with resected brain glioblastomas who presented early clinical and neuroradiological worsening after the completion of the Stupp protocol. Its aim is to discuss the occurrence of early radionecrosis. METHODS Fifty patients with brain glioblastoma treated by surgical resection and Stupp protocol were reviewed; 15 among them (30%) had early clinical and neuroradiological worsening at the 6-month follow-up. The MR spectroscopy and surgical findings of these patients are reviewed. RESULTS MR spectroscopy was in favour of tumour recurrence in 14 among 15 patients and showed radionecrosis in one. Among 10 patients who were reoperated on, 7 had histologically verified tumour recurrence or regrowth, whereas in 3 histopathology showed necrosis without evidence of tumour. The 7 patients with tumour progression had prevalence of focal neuroradiological signs (6/7) and a survival of 7.5-12 months (median survival 10 months). The 4 patients with early radionecrosis (including one patient who was not reoperated on) had clinical worsening with mental deterioration, confusion and ataxia, and MR spectroscopy positive for tumour recurrence in 3. Three were alive 24-30 months after the end of the radiotherapy, whereas one died at 40 months. CONCLUSION Early radionecrosis after the Stupp protocol is not a rare event due to the radiosensitization effect of temozolomide. This phenomenon may predict a durable response to radiotherapy. MR spectroscopy may simulate tumour recurrence. A correct diagnosis is necessary to avoid useless reoperations and incorrect withdrawal of temozolomide.

Dramatic response to levetiracetam in post-ischaemic Holmes’ tremor

Holmes’ tremor refers to an unusual combination of rest, postural and kinetic tremor of extremities. Common causes of Holmes’ tremor include stroke, trauma, vascular malformations and multiple sclerosis, with lesions involving the thalamus, brain stem or cerebellum.1 Although some drugs (eg, levodopa and dopaminergic drugs, clonazepam and propranolol) have been occasionally reported to give some benefit, medical treatment of Holmes’ tremor is unsatisfactory, and many patients require thalamic surgery to achieve satisfactory control.2 We report a patient in whom post-ischaemic Holmes’ tremor dramatically responded to levetiracetam treatment. A 61-year-old right-handed man with a history of polycythaemia vera suddenly developed dizziness, diplopia and ataxia in February 2006. A CT scan showed a left cerebellar haemorrhagic infarction. Within a few days, his neurological state gradually improved. However, in March 2006, a coarse, slowly progressive tremor arose in his left upper extremity. On admission to our hospital, the man was alert and orientated. His blood pressure was 130/85 mm Hg and pulse 80/min. Serum electrolytes, urea, creatinine, bicarbonate, liver transaminases, thyroxine, triiodothyronine, and thyroid-stimulating hormone were normal. Blood analysis showed 5.8×103 cells/mm3 of red blood cells, 17 g/dl …

Brain Changes in Kallmann Syndrome

BACKGROUND AND PURPOSE: Kallmann syndrome is a rare inherited disorder due to defective intrauterine migration of olfactory axons and gonadotropin-releasing hormone neurons, leading to rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Concomitant brain developmental abnormalities have been described. Our aim was to investigate Kallmann syndrome–related brain changes with conventional and novel quantitative MR imaging analyses. MATERIALS AND METHODS: Forty-five male patients with Kallmann syndrome (mean age, 30.7 years; range, 9–55 years) and 23 age-matched male controls underwent brain MR imaging. The MR imaging study protocol included 3D-T1, FLAIR, and diffusion tensor imaging (32 noncollinear gradient-encoding directions; b-value = 800 s/mm2). Voxel-based morphometry, sulcation, curvature, and cortical thickness analyses and tract-based spatial statistics were performed by using Statistical Parametric Mapping 8, FreeSurfer, and the fMRI of the Brain Software Library. RESULTS: Corpus callosum partial agenesis, multiple sclerosis–like white matter abnormalities, and acoustic schwannoma were found in 1 patient each. The total amount of gray and white matter volume and tract-based spatial statistics measures (fractional anisotropy and mean, radial, and axial diffusivity) did not differ between patients with Kallmann syndrome and controls. By specific analyses, patients with Kallmann syndrome presented with symmetric clusters of gray matter volume increase and decrease and white matter volume decrease close to the olfactory sulci; reduced sulcal depth of the olfactory sulci and deeper medial orbital-frontal sulci; lesser curvature of the olfactory sulcus and sharper curvature close to the medial orbital-frontal sulcus; and increased cortical thickness within the olfactory sulcus. CONCLUSIONS: This large MR imaging study on male patients with Kallmann syndrome featured significant morphologic and structural brain changes, likely driven by olfactory bulb hypo-/aplasia, selectively involving the basal forebrain cortex.

Unilateral proptosis in thyroid eye disease with subsequent contralateral involvement: retrospective follow-up study

BackgroundThe purpose of this retrospective follow-up study is to evaluate the prevalence of patients with thyroid eye disease presenting with apparent unilateral proptosis and determine the occurrence of exophthalmos in contralateral non-proptotic eye over the time. Associated features with this event were evaluated.MethodsA cohort of 655 consecutive patients affected by thyroid eye disease with a minimum follow-up of 10 years was reviewed. Exophthalmos was assessed by using both Hertel exophthalmometer and computed tomography (CT). The influence of age, gender, hormonal status and of different therapies such as corticosteroids, radiotherapy and surgical decompression on this disease progression was evaluated.ResultsA total of 89 patients (13.5%) (95% confidence interval [CI] 15%-10%) had clinical evidence of unilateral exophthalmos at the first visit. Among these, 13 patients (14%) (95% CI 22%-7%) developed subsequent contralateral exophthalmos. The increase of protrusion ranged from 2 to 7 mm (mean of 4.2). The time of onset varied from 6 months to 7 years (mean time: 29 months). Smoking status, young age and surgical decompression are significantly associated with development of contralateral proptosis (p< .05).ConclusionsAsymmetric thyroid eye disease with the appearance of unilateral exophthalmos at the initial examination is a fairly frequent event, while subsequent contralateral proptosis occurs less commonly. However, physicians should be aware that young patients, particularly if smokers, undergoing orbital decompression in one eye may need further surgery on contralateral side over time.

Diffusion Weighted MR Imaging of Primary and Recurrent Middle Ear Cholesteatoma: An Assessment by Readers with Different Expertise

Introduction and Purpose. Diffusion weighted imaging (DWI) has been proven to be valuable in the diagnosis of middle ear cholesteatoma. The aims of our study were to evaluate the advantage of multi-shot turbo spin echo (MSh TSE) DWI compared to single-shot echo-planar (SSh EPI) DWI for the diagnosis of cholesteatoma. Material and Methods. Thirty-two patients with clinical suspicion of unilateral cholesteatoma underwent preoperative MRI (1.5T) with SSh EPI and MSh TSE. Images were separately analyzed by 4 readers with different expertise to confirm the presence of cholesteatoma. Sensitivity, specificity, diagnostic accuracy, and positive (PPV) and negative predictive values (NPV) were assessed for each observer and interrater agreement was assessed using kappa statistics. Diagnosis was obtained at surgery. Results. Overall MSh TSE showed higher diagnostic accuracy and lower negative predictive value (NPV) compared to conventional SSh EPI. Interreader agreement between the observers revealed the superiority of MSh TSE compared to SSh EPI. Interrater agreement among all the four observers was higher by using MSh TSE compared to SSh EPI. Conclusion. Our findings suggest that MSh TSE DWI has higher sensitivity for detection of cholesteatoma and lower probability of misdiagnosis. MSh TSE DWI is useful in guiding less experienced observers to the diagnosis.

Paravertebral High Cervical Chordoma A Case Report

Spinal chordomas are more often located on the midline and are associated with marked destruction of the vertebral bodies. We report a rare case of large cervical (C2-C3) right lateral paravertebral chordoma extending into the spinal canal through a very enlarged intervertebral foramen. The tumor was initially diagnosed as a mucous adenocarcinoma on a percutaneous needle biopsy. However, the neuroradiological features, including the well-defined tumor margins, the regular and sclerosing lytic bone changes with regular enlargement of the intervertebral C2-C3 foramen, were in favor of a more slowly growing lesion, such as schwannoma or neurofibroma. At surgery a well-demarcated capsulated tumor involving the nerve root was partially resected. Histology was in favor of a low-grade chordoma (Ki-67/MIB-1<1%). Postoperative proton beam therapy was also performed. The differential neuroradiological diagnosis is discussed.

Bilateral hypoplasia of the internal carotid arteries with basilar aneurysm

We report a rare case of bilateral hypoplasia of the internal carotid arteries with an associated aneurysm of the basilar tip, studied by CT angiography, MR angiography and digital angiography. The patient became symptomatic with an episode of loss of consciousness, likely due to reduced blood perfusion. The other 20 reported cases of bilateral carotid hypoplasia (only four of which with an associated aneurysm) are reviewed. The findings of noninvasive procedures (including narrowing of the carotid canals on CT) may lead to a correct diagnosis before angiography is performed; they may also help to differentiate angiographic narrowing of the hypoplastic internal carotids from the string sign often observed in some acquired conditions.

Cervical Spinal Brucellosis: A Diagnostic and Surgical Challenge

) can cause human infection.Brucellosis is a health issue that sometimes leads to epidemics inmany regions of the world, presenting a higher incidence in theMediterranean basin, the Arabian peninsula, the Indian subconti-nent, and South America. Although the sanitation in these areas hascontinuously improved, the reduction of incidence of the disease isnot significant, and there are frequent case reports. In thesecountries the disease can spread to humans eating or drinkinginfected animal products, breathing in the organism, or by directcontact with infected tissue such as the bacteria entering the bodythrough skin wounds (8, 18). The most common way to be infectedis by eating or drinking contaminated milk products.In developed countries human brucellosis is primarily an occupa-tion-related disease, occurring mostly among veterinarians, lab-oratory workers, and farmers. BIBL Direct person-to-personspread of brucellosis is extremely rare. Mothers who are breast-feeding may transmit the infection to their infants. Sexual trans-mission has also been reported (7).Brucellosis can affect the gastrointestinal, skeletal, hepatobiliary, car-diovascular, and respiratory systems. Skeletal system involvementsare the most common focal complications and has been described in10%–85% of patients depending on the species of