Paola Bini

Cerebrospinal fluid levels of tau phosphorylated at threonine 181 in patients with Alzheimer’s disease and vascular dementia

In 31 patients with probable Alzheimer’s disease (AD), 19 with probable vascular dementia (VaD) and 20 with Possible AD and Possible VaD, cerebrospinal fluid (CSF) tau levels hyperphosphorylated at threonine 181 (Ptau) were measured by ELISA. Thirty-six age-matched subjects were used as controls. The severity of the cognitive decline was assessed at the time of CSF analysis and after a 12-month follow-up. The groups had comparable age, degree of cognitive impairment and disease duration; these parameters were not related to P-tau levels. P-tau discriminated between demented patients and controls, but no significant difference emerged between AD and the other groups. By contrast, higher P-tau values were found to predict, independently of the clinical diagnosis, a more rapid evolution of cognitive decline. Whether these findings are due to a lack of CSF P-tau specificity or to the low reliability of clinical and radiological criteria remains unclear. P-tau may be useful in the evaluation of disease evolution, by predicting the rate of cognitive decline.

Changes in nutritional status and body composition during enzyme replacement therapy in adult-onset type II glycogenosis.

Background:  In adult glycogen storage disease type II (GSDII), a single‐gene mutation causes reduction of the lysosomal enzyme acid alpha‐glucosidse. This produces a chronic proximal myopathy with respiratory involvement. Enzyme replacement treatment (ERT) has recently become available and is expected to improve muscle strength. This should result in increased lean body mass. In this study we evaluate body composition and nutritional status in GSDII, and assess whether these parameters changed during treatment.

Galanin and α-MSH autoantibodies in cerebrospinal fluid of patients with Alzheimer's disease

BACKGROUND Neuropeptides galanin and α-melanocyte-stimulating hormone (α-MSH) are involved in the regulation of memory and appetite. Increased galanin and decreased α-MSH levels were reported in postmortem brains of patients with Alzheimers disease (AD) but the underlying mechanisms are uncertain. Here we studied if autoantibodies (autoAbs) reacting with galanin and α-MSH are altered in AD. METHODS Levels of free and total IgG autoAbs reacting with galanin and α-MSH were measured in sera and cerebrospinal fluid (CSF) of 18 subjects with AD and in 15 age-matched non-demented controls. Values were correlated with Mini-Mental State Examination (MMSE) score, body mass index (BMI) and CSF levels of AD biomarkers. RESULTS CSF levels of total but not free IgG autoAbs against galanin were increased in AD, resulting in increased percentage of galanin autoAbs present as immune complexes. CSF levels of galanin total autoAbs and α-MSH free autoAbs correlated negatively with the severity of cognitive impairment as measured by MMSE. Both total and free autoAbs against galanin and α-MSH in CSF correlated negatively with age in AD patients but not in controls. CSF levels of galanin autoAbs and free α-MSH AutoAbs negatively correlated with CSF levels of t-Tau, p-Tau and ratios of t-Tau/Aβ42 or p-Tau/Aβ42 in AD patients but not in controls. CONCLUSIONS AutoAbs reacting with galanin and α-MSH are present in CSF and are associated with clinical characteristics of AD patients. The functional significance and therapeutic potential of these autoAbs should be further clarified.

Spinal hemorrhage in eosinophilic granulomatosis with polyangiitis (Churg–Strauss)

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as a Churg–Strauss syndrome [1], is a rare systemic small vessel vasculitis mainly affecting people aged 40–60 years without gender predominance [2, 3]. Asthma, eosinophilia, chronic paranasal sinusitis, nasal polyposis, non-fixed pulmonary infiltrates, and myocarditis are typical findings of EGPA [4]. Neurologic involvement is frequently observed and peripheral nervous system (PNS) is affected in 59–86 % of patients, mainly in the form of peripheral neuropathy [5]. On the contrary, central nervous system (CNS) involvement is described in less than 10 % of cases [5]. The most common CNS manifestations are cerebral infarction and diffuse encephalopathy, while cerebral hemorrhages have been seldom associated with EGPA [6] and only one case of spinal subarachnoid hemorrhage has been previously reported in the early 1980s [7]. In June of 2012, a 31-year-old pregnant Caucasian woman with a long-term history of asthma and rhinitis on the day of the delivery presented with high spiking fever (up to 39.5 C) and arthralgias, disappearing in a few hours. Further similar episodes were then observed in the subsequent months without other additional findings. In August 2012, painful paresthesias in left hand, right arm, and dorsal surface of right foot appeared, together with bilateral distal upper limbs weakness. Electromyography/ electroneurography (EMG/ENG) confirmed a severe sensory-motor axonal neuropathy, predominant in upper limbs, characterized by patchy pattern as in vasculitic mononeuritis multiplex. Laboratory investigations showed an increase of inflammatory markers (ESR 58 mm/h, CPR 6.9 mg/dl) and leukocytosis (21,000/ll) with eosinophilia (63 %). Antineutrophil cytoplasmic antibodies (ANCA) were positive both in IIF (p-ANCA pattern) and in ELISA (anti-MPO specificity). Because of headache and neck stiffness appearance, brain MRI was performed, displaying maxillary and sphenoid sinusitis without CNS pathological findings. After the exclusion of underlying infections, the patient was diagnosed with EGPA and methylprednisolone 1 mg/kg/ day i.v. was started. Despite corticosteroid treatment, headache and neck stiffness persisted, global left upper limb weakness worsened in particular arm and wrist extension, and brisk left supinator tendon reflex appeared. Lumbar puncture revealed hemorrhagic cerebrospinal fluid, with a protein value of 755 mg/dl, glucose value of 23 mg/ dl, and 205 cells (neutrophils and red blood cells). HumanCMV and HSV infections were excluded by real-time PCR on cerebrospinal fluid, as well as other infectious processes. Spinal MRI was performed showing cervical and dorsal subarachnoid bleeding with spinal cord compression and C6–C7 intramedullary hyperintensity on the left side (Figs. 1a, 2a). Intravenous steroid (methylprednisolone 1 mg/kg/day i.v. for 6 days) was administered, followed by oral prednisone (75 mg/day) with subsequent tapering until suspension at 12 weeks. L. Diamanti (&) G. Berzero P. Bini S. Ravaglia E. Marchioni Neurology Department, IRCCS National Neurological Institute C. Mondino, University of Pavia, via Mondino 2, 27100 Pavia, Italy e-mail: luca.diamanti@mondino.it

Can genes influencing muscle function affect the therapeutic response to enzyme replacement therapy (ERT) in late-onset type II glycogenosis?

The purpose of this study is to analyze the role of genes known to influence muscle performances on the outcome after enzyme replacement treatment (ERT) in type II Glycogenosis (GSDII). We analyzed 16 patients receiving ERT for ≥two years. We assessed the changes in muscle strength by hand-held dynamometry, muscle mass by quantitative MRI, and resistance to exercise by the 6-minute walking test. Exercise gene assessment included angiotensin converting enzyme insertion/deletion polymorphism (ACE), alpha-actinin3 R577X polymorphism (ACTN3), and peroxisome proliferator activated receptor alpha G/C polymorphism (PPARα). Independent of disease severity, one third of patients had a poor response to ERT, which was found to be associated with ACE DD genotype. The ACTN3 null polymorphism appeared to exert a positive effect on treatment efficacy, while PPARα did not seem to exert any influence at all. We conclude that poor treatment outcome in ACE DD genotypes is in line with previous observation of a worse disease course in this subpopulation, and suggests the need for a more careful follow-up and individualized treatment approaches for these patients. Exercise genes may provide a new opportunity for studying the outcome after treatment and the muscle regeneration abilities in other models of genetic myopathies.

Septo-optic dysplasia and psychiatric disorders: a case report.

BackgroundSepto-optic dysplasia, a variable combination of abnormalities of cerebral midline structures, is a clinically heterogeneous syndrome in which the midline defects may be implicated in psychiatric disturbances. ObjectiveTo describe a case of septo-optic dysplasia associated with depression and psychosis and to discuss the role of these developmental abnormalities in psychiatric disturbances. MethodsThe patients clinico-anamnestic, neuroradiologic, neuropsychiatric, endocrinologic, ophthalmologic, and genetic profile was evaluated. ConclusionsDevelopmental abnormalities due to disruption of the complex neural network linking the septum pellucidum with other limbic structures may have been involved in the affective and psychotic disturbances observed in our patient.

Meningeal Melanomatosis: A Challenge for Timely Diagnosis

Neoplastic meningitis is a central nervous system complication that occurs in 3–5% of patients with cancer. Although most commonly seen in patients with disseminated disease, in a small percentage of patients, it may be the initial manifestation of cancer or even primitive in origin. In the absence of cancer history, the diagnosis of neoplastic meningitis may be challenging even for expert neurologists. Prognosis is poor, with a median overall survival of weeks from diagnosis. In the retrospective study herein, we described three cases of meningeal melanomatosis in patients without previous cancer history. The patients were diagnosed with significant delay (17 to 47 weeks from symptom onset) mainly due to the deferral in performing the appropriate testing. Even when the diagnosis was suspected, investigations by MRI, cerebrospinal fluid, or both proved at times unhelpful for confirmation. Prognosis was dismal, with a median survival of 4 weeks after diagnosis. Our observations are a cue to analyze the main pitfalls in the diagnosis of neoplastic meningitis in patients without cancer history and emphasize key elements that may facilitate early diagnosis.