Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood.

Twenty years after the first description of combined hypopituitarism (CPHD) caused by PROP1 mutations, the phenotype of affected subjects is still challenging for clinicians. These patients suffer from pituitary hormone deficits ranging from IGHD to panhypopituitarism. ACTH deficiency usually develops later in life. Pituitary size is variable. PROP1 mutation is the most frequent in familial congenital hypopituitarism (CH). Reports on initiation of hormonal replacement including growth hormone (GH) in adults with CH are scarce. We identified 5 adult siblings with CPHD due to PROP1 mutation (301-302delAG), aged 36-51 years (4 females), never treated for hormone deficiencies. They presented with short stature (SD from - 3.7 to - 4.7), infantile sexual characteristic, moderate abdominal obesity and low bone mineral density in 3 of them. Complete hypopituituitarism was confirmed in three siblings, while two remaining demonstrated GH, TSH, FSH and LH deficiencies. Required hormonal replacement including rhGH was initiated in all patients. After several months necessity for hydrocortisone replacement developed in all patients. After 2 years of continual replacement therapy, BMD and body composition (measured by DXA-dual X-ray absorptiometry) improved in all subjects, most prominently in two younger females and the male sibling. Besides rhGH therapy, these three patients have received sex hormones contributing to the favorable effect. The male sibling was diagnosed with brain glioblastoma two years following complete hormonal replacement. This report provides important experience regarding hormonal replacement, particularly rhGH treatment, in adults with long-term untreated CH. Beneficial effect of such therapy are widely acknowledged, yet these subjects could be susceptible to certain risks of hormonal treatment initiated in adulthood. Careful and continual clinical follow-up is thus strongly advised.

Single center study of 53 consecutive patients with pituitary stalk lesions.

BACKGROUND: The etiological spectrum of pituitary stalk lesions (PSL) is wide and yet specific compared to the other diseases of the sellar and suprasellar region. Because of the pituitary stalk's (PS) critical location and role, biopsies of these lesions are rarely performed, and their underlying pathology is often a conundrum for clinicians. A pituitary MRI in association with a clinical context can facilitate their diagnosis. AIM: To present the various causes of PSL-their clinical, hormonal, histopathological, and MRI characteristics in order to gain better insight into this pathology. METHOD: A retrospective observational study consisting of 53 consecutive patients with PSL of the mean age 32 ± 4.2 years (range 6-67), conducted at the Department for Neuroendocrinology, Clinical Center of Serbia 2010-2018. RESULTS: Congenital malformations were the most common cause of PSL in 25 of 53 patients (47.1%), followed by inflammatory (9/53; 16.9%) and neoplastic lesions (9/53; 16.9%). The exact cause of PSL was established in 31 (58.4%) patients, of whom 23 were with congenital PS abnormalities and 8 with histopathology of PSL (7 neoplastic and 1 Langerhans Cell Hystiocytosis). A probable diagnosis of PSL was stated in 12 patients (22.6%): 6 with lymphocytic panhypophysitis, while Rathke cleft cyst, tuberculosis, dissemination of malignancy in PS were each diagnosed in 2 patients. In 10 patients (18.8%), the etiology of PSL remained unknown. CONCLUSION: Due to the inability of establishing an exact diagnosis, the management and prognosis of PSL are difficult in many patients. By presenting a wide array of causes implicated in this condition, we believe that our study can aid clinicians in the challenging cases of this pathology.

Correlates of Executive Functions in Multiple Sclerosis Based on Structural and Functional MR Imaging: Insights from a Multicenter Study.

Purpose To study the concomitant use of structural and functional magnetic resonance (MR) imaging correlates to explain information processing speed (IPS) and executive function (EF) in multiple sclerosis (MS). Materials and Methods Local ethics committee approval was obtained at all sites for this prospective, multicenter study. All subjects provided written informed consent. Twenty-six patients with relapsing-remitting MS and 32 healthy control subjects from four centers underwent structural and functional MR imaging, including a go/no-go task and neuropsychological assessment. Subtests of the Brief Repeatable Battery of Neuropsychological Tests, the Wisconsin Card Sorting Test, and the performance with the functional MR imaging paradigm were used as estimates of IPS and EF. Activation of the thalamus and the inferior frontal gyrus (pars triangularis), thalamic volume, T2 lesion load, and age were used to explain IPS and EF in regression models. Results Compared with control subjects, patients showed increased activation in a frontoparietal network, including both thalami, during the execution of the go/no-go task. Patients had decreased thalamic volume (P < .001). Among tested variables, thalamic volume (ß = 0.606, P = .001), together with thalamic activation (ß = -0.410, P = .022), were the best predictors of IPS and EF and helped explain 52.7% of the variance in IPS and EF. Conclusion This study highlights the potential of the combined use of functional and morphologic parameters to explain IPS and EF in patients with relapsing-remitting MS and confirms the central role of the thalamus as a relay station in executive functioning. (©) RSNA, 2016.

Voxel-wise mapping of cervical cord damage in multiple sclerosis patients with different clinical phenotypes.

OBJECTIVE: To apply voxel-based methods to map the regional distribution of atrophy and T2 hyperintense lesions in the cervical cord of multiple sclerosis (MS) patients with different clinical phenotypes. METHODS: Brain and cervical cord 3D T1-weighted and T2-weighted scans were acquired from 31 healthy controls (HC) and 77 MS patients (15 clinically isolated syndromes (CIS), 15 relapsing-remitting (RR), 19 benign (B), 15 primary progressive (PP) and 13 secondary progressive (SP) MS). Hyperintense cord lesions were outlined on T2-weighted scans. The T2- and 3D T1-weighted cord images were then analysed using an active surface method which created output images reformatted in planes perpendicular to the estimated cord centre line. These unfolded cervical cord images were co-registered into a common space; then smoothed binary cord masks and lesion masks underwent spatial statistic analysis (SPM8). RESULTS: No cord atrophy was found in CIS patients versus HC, while PPMS had significant cord atrophy. Clusters of cord atrophy were found in BMS versus RRMS, and in SPMS versus RRMS, BMS and PPMS patients, mainly involving the posterior and lateral cord segments. Cord lesion probability maps showed a significantly greater likelihood of abnormalities in RRMS, PPMS and SPMS than in CIS and BMS patients. The spatial distributions of cord atrophy and cord lesions were not correlated. In progressive MS, regional cord atrophy was correlated with clinical disability and impairment in the pyramidal system. CONCLUSIONS: Voxel-based assessment of cervical cord damage is feasible and may contribute to a better characterisation of the clinical heterogeneity of MS patients.

What microsurgeon, orthopaedic and plastic surgeon should know about bionic hand.

Hand loss is a catastrophic event that generates significant demands for orthopedics and prosthetics. In the course of history, prostheses evolved from passive esthetic replacements to sophisticated robotic hands. Yet, their actuation and particularly, their capacity to provide patients with sensations, remain an unsolved problem. Sensations associated with the hand, such as touch, pain, pressure and temperature detection are very important, since they enable humans to gather information from the environment. Recently, through a synergistic multidisciplinary effort, medical doctors and engineers have attempted to address these issues by developing bionic limbs. The aim of the bionic hands is to replace the amputated hands while restoring sensation and reintroducing hand-motor control. Recently, several different approaches have been made to interface this sophisticated prosthesis with residual neuro-muscular structures. Different types of implants, such as intramuscular, epineural and intraneural, each have their own complementary advantages and disadvantages, which are discussed in this paper. After initial trials with percutaneous leads, present research is aimed at making long-term implantable electrodes that give rich, natural feedback and allow for effortless control. Finally, a pivotal part in the development of this technology is the surgical technique which will be described in this paper. The surgeons' insights into this procedure are given. These kinds of prostheses compared with the classic one, hold a promise of dramatic health and quality of life increase, together with the decrease the rejection rate.

Proton magnetic resonance spectroscopy and apparent diffusion coefficient in evaluation of solid brain lesions.

BACKGROUND/AIM: Advanced magnetic resonance techniques can provide insight in physiological changes within pathological canges and contribute to better distinquishing between different tumor types and their discrimination from non-neoplastic lesions. The aim of this study was to evaluate the role of proton magnetic resonance spectroscopy (1H-MRS) and apparent diffusion coefficients (ADC) in distinguishing intracranial glial tumors from tumor like nonneoplastic lesions, as well as for differentiating high- from low-grade gliomas. METHODS: This retrospective study included 47 patients with solid brain lesions (25 nonneoplastic, 14 low-grade and 8 anaplastic glial tumors). In all patients 1H-MRS (at a TE of 135 ms and 30 ms) and diffusion-weighted imaging (DWI) were performed. The choline to creatine (Cho/Cr), choline to N-acetyl aspartate (Cho/NAA), N-acetyl aspartate to creatine (NAA/Cr) and myoinositol to creatine (mIn/Cr) ratios and the apparent diffusion coefficient (ADC) were determined. RESULTS: The Cho/Cr ratio was significantly higher in glial tumors grade II than in non-neoplastic lesions (p = 0.008) and in glial tumors grade III than in non-neoplastic lesions (p = 0.001). The Cho/NAA ratio was significantly higher in glial tumors grade II than in non-neoplastic lesions (p = 0.037). AADC/ADC between glial tumors grade II and glial tumors grade III showed a statistical significance (p = 0.023). CONCLUSION: Our study showed that 1H-MRS and apparent diffusion coefficients can help in evaluation and differentiation of solid brain lesions.

Significance of magnetic resonance imaging in differential diagnosis of nontraumatic brachial plexopathy.

BACKGROUND/AIM: Nontraumatic brachial plexopathies may be caused by primary or secondary tumors, radiation or inflammation. The aim of this study was to present the significance of MRI in revealing the cause of nontraumatic brachial plexopathy. METHODS: A two-year retrospective study included 22 patients with nontraumatic brachial plexopathy. In all the patients typical clinical findings were confirmed by upper limb neurophysiological studies. In all of them MRI of brachial plexus was performed by 1.5 T scanner in T1 and T1 FS sequence with and without contrast, as well as in T2 and T2 FS sequences. RESULTS: Seven (32%) patients had brachial plexopathy with signs of inflammatory process, 5 (23%) patients had secondary tumors, in 4 (18%) patients multifocal motor neuropathy was established and in the same number (18%) of the patients postradiation fibrosis was found. Two patients (9%) had primary neurogenic tumors. CONCLUSION: According to the results of this study MRI is a method which may determine localization and cause of brachial plexopathy. MRI can detect focal nerve lesions when other methods fail to find them. Thus, MRI has a direct impact on further diagnostic and therapeutical procedures.