Sporadic hereditary neuropathies misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: Pitfalls and red flags

Hereditary neuropathies may be misdiagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). A correct diagnosis is crucial for avoiding unnecessary therapies and access genetic counseling. We report on nine patients (seven men, mean age 49.2 ± 16.1) diagnosed with and treated as CIDP, in whom mutations or variants of unknown significance (VUS) in genes associated with hereditary neuropathies were reported. All underwent neurological and neurophysiological examination, eight also cerebrospinal fluid (CSF) analysis. In 4/9, nerve ultrasound and/or MR‐neurography were performed. All the patients complained of progressive upper or lower limbs sensory‐motor symptoms, with heterogeneous disease duration (1‐34 years, mean 8.6 ± 10.8). Neurophysiology showed demyelinating signs in seven patients, mixed findings with predominant axonal damage in two patients. Neuroimaging disclosed diffuse abnormalities at proximal and distal segments. Molecular screening showed PMP22 duplication in two patients, mutations in the MPZ, EGR2, and GJB1 genes were reported in each of the remaining patients. The two patients with mixed neurophysiological findings had p.Val30Met mutation in the transthyretin gene. Two patients had VUS in the MARS and HSPB1 genes. Four patients had partial response to immunomodulant therapies, and CSF and neurophysiological features suggesting an inflammatory condition concomitant with the hereditary neuropathy. Hereditary neuropathy may be misdiagnosed with CIDP. The most common pitfalls are CSF (high protein levels and oligoclonal bands), incorrect interpretation of neurophysiology, and transient benefit from therapies. Neuroimaging may be helpful in cases with atypical presentations or when severe axonal damage complicate the neurophysiological interpretation.     

Pure midbrain ischemia and hypoplastic vertebrobasilar circulation

Isolated midbrain infarction is rare and little is known about etiology and patient’s long-term follow up. We aimed to describe the clinical features, the causative diseases and the outcome of patients with isolated midbrain infarction who were admitted to our center, focusing on vascular abnormalities of posterior circulation. All patients with first acute ischemic stroke limited to the midbrain were included and their demographic features, neurological symptoms, neuroimaging data, and cardiovascular risk factors were recorded. Functional outcome, using modified Rankin scale, was assessed at discharge and at the 3 month follow up evaluation. We found nine patients with acute isolated midbrain infarction, representing 0.61 % of all ischemic stroke admitted to our center. The most common cause of stroke was small-vessel disease (88.8 %). At stroke onset, none of the patients had consciousness disturbances, and four patients (44.4 %) had gait impairment, five patients (55.5 %) presented with diplopia due to involvement of the third nerve or fascicular type of third-nerve palsy, seven patients (77.7 %) had vascular anomalies of vertebrobasilar circulation: the most frequent was vertebral artery hypoplasia [four patients (44.4 %)]. At follow up evaluation, seven patients (77.7 %) had a good functional outcome and no patients experienced recurrence of cerebrovascular events. As isolated midbrain infarction is uncommon, specific ocular motor signs, mainly third-nerve palsy, may help to identify and localize the mesencephalic infarct. Abnormalities in vertebrobasilar circulation, such as hypoplastic basilar or vertebral artery, are frequently associated with isolated midbrain ischemia. The hypoplastic vertebrobasilar system may predispose to posterior ischemic stroke.     

Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD

Granulin (GRN) mutations have been identified as a major cause of frontotemporal lobar degeneration (FTLD) by haploinsufficiency mechanism, although their effects on brain tissue dysfunction and damage still remain to be clarified. In this study, we investigated the pattern of neuroimaging abnormalities in FTLD patients, carriers and noncarriers of GRN Thr272fs mutation, and in presymptomatic carriers. We assessed regional gray matter (GM) atrophy, and resting (RS)-functional magnetic resonance imaging (fMRI). The functional connectivity maps of the salience (SN) and the default mode (DMN) networks were considered. Frontotemporal gray matter atrophy was found in all FTLD patients (more remarkably in those GRN Thr272fs carriers), but not in presymptomatic carriers. Functional connectivity within the SN was reduced in all FTLD patients (again more remarkably in those mutation carriers), while it was enhanced in the DMN. Conversely, presymptomatic carriers showed increased connectivity in the SN, with no changes in the DMN. Our findings suggest that compensatory mechanisms of brain plasticity are present in GRN-related FTLD, but with different patterns at a preclinical and symptomatic disease stage.     

Nerve ultrasound in hereditary transthyretin amyloidosis: red flags and possible progression biomarkers

Journal of Neurology - Diagnostic delay of hereditary transthyretin amyloidosis (ATTRv, v for variant) prevents timely treatment and, therefore, concurs to the mortality of the disease. The aim of...     

Evidence of the effect of adjunct ultrasound screening in women with mammography-negative dense breasts: interval breast cancers at 1 year follow-up

Surveillance of interval cancers (IC) provides a measure of breast screening efficacy. Increased breast density is a predictor of breast cancer risk and of the risk of IC in screening. Improving screening sensitivity in women with dense breasts, through adjunct ultrasound (US), may potentially reduce IC; however this has not been proven. We report on first-year IC in a retrospective cohort of 8865 women who had 19,728 screening examinations (2001-2006): women with non-dense (D1-D2) breasts received mammography (M) screening, and women with dense (D3-D4) breasts also received ultrasound. Data linkage with both hospital discharge records and cancer registry databases was used to identify IC.Underlying cancer rates (cancers observed within 1-year from screening) were 6.3/1000 screens in the D1-D2 group and 8.3/1000 screens in the D3-D4 group. Cancer detection rate (CDR) was 5.98/1000 in all screening examinations; in D3-D4 breasts ultrasound had an additional CDR of 4.4/1000 screens. There were 21 first-year IC, an overall interval cancer rate (ICR) of 1.07/1000 negative screens: 0.95/1000 in women <50 years and 1.16/1000 screens in women ?50 years. ICR by breast density were 1.0/1000 negative screens in D1-D2, and 1.1/1000 negative screens in D3-D4. Interval cancers were early stage (in situ or small invasive) cancers, almost all were node-negative. Screening sensitivity was 83.5% for mammography alone in D1-D2 breasts relative to 86.7% for mammography with ultrasound in D3-D4 breasts.Our study shows that including ultrasound as adjunct screening in women with D3-D4 breasts brings the IC rate to similar levels as IC in non-dense breasts - this suggests that additional cancer detection by ultrasound is likely to improve screening benefit in dense breasts, and supports the implementation of a randomised trial of adjunct ultrasound in women with increased breast tissue density.     

Grey Matter Density Predicts the Improvement of Naming Abilities After tDCS Intervention in Agrammatic Variant of Primary Progressive Aphasia

Agrammatic variant primary progressive aphasia is a neurodegenerative disorder specifically characterized by language deficits. A recent study has demonstrated a beneficial effect of transcranial direct current stimulation (tDCS) in combination with language training on naming accuracy in these patients. The aim of the study was to evaluate whether the improvement of naming accuracy after tDCS during language training was related to regional grey matter (GM) density. Eighteen avPPA patients underwent a brain magnetic resonance imaging before receiving a treatment that consisted of tDCS over the left dorsolateral prefrontal cortex during individualized language training (10 daily therapy sessions, 5 days per week from Monday to Friday). Performances on neuropsychological tests and naming of objects (treated and untreated) and actions were assessed at baseline, post-treatment  and 3 months after treatment. Correlations between individual changes after treatment on neuropsychological tests and on picture naming task and voxel-based GM volume at baseline were performed. We found that the improvement in the naming of treated objects was positively correlated with GM volume in the left fusiform, left middle temporal, and right inferior temporal gyri whereas action naming change was related to GM density in the left middle temporal gyrus. In conclusion baseline density of GM in these brain regions was associated with greater treatment response on naming performances, suggesting that intervention in early disease stages might be most successful. These findings have implication for designing future rehabilitation protocols in language variants of frontotemporal dementia.     

Immunological and gadolinium-DTPA MRI evaluation of relapsing remitting multiple sclerosis

The levels of lymphocytes, blood lymphocytes subsets (CD3+, CD4+, CD8+, DR+, CD25+, CD4+, CD45RA+, CD4+, CD29+ cells) and sIL-2r of 10 patients affected by relapsing-remitting multiple sclerosis were serially studied. The identification of the activity of the disease was made by gadolinium-DTPA (Gd-DTPA) MRI. The immunological determinations and the MRI of the brain and spinal cord were performed every 14th day for a period of three months. No significant difference of the immunological values were found between the presence and the absence of Gd-DTPA enhancing areas, except lymphocytes (p < 0.05). These immunological parameters, evaluated in the peripheral blood, are not a marker of disease activity in relapsing-remitting MS patients.     

Superficial liposuction: A new application of the technique for aged and flaccid skin

From 1982 to 1991, 2500 patients underwent liposuction to thin the superficial areolar layer of fat. The patients were of all ages and had different types of skin. From the results the author concludes that the new superficial liposculpting, based on the controlled scar retraction of the thin cutaneous adipose flap remaining after the treatment, allows for very good results even in very flaccid and aged skin. A digital molding of the residual fat also improves the contouring. So-called cellulite is finally meliorated.Presented at the First and Second International RAPS Congress, Sao Paulo, Brasil, March 1989 and 1991 and at the Nineth LSNA Meeting, Seattle, Washington, September 1991