Stroke and migraine is there a possible comorbidity?

The association between migraine and stroke is still a dilemma for neurologists. Migraine is associated with an increased stroke risk and it is considered an independent risk factor for ischaemic stroke in a particular subgroup of patients. The pathogenesis is still unknown even if several studies report some common biochemical mechanisms between these two diseases. A classification of migraine-related stroke that encompasses the full spectrum of the possible relationship between migraine and stroke includes three main entities: coexisting stroke and migraine, stroke with clinical features of migraine, and migraine-induced stroke. The concept of migraine-induced stroke is well represented by migrainous infarction and it is described in the revised classification of the International Headache Society (IHS), representing the strongest demonstration of the relationship between ischaemic stroke and migraine. A very interesting common condition in stroke and migraine is patent foramen ovale (PFO) which could play a pathogenetic role in both disorders. The neuroradiological evidence of subclinical lesions most typical in the white matter and in the posterior artery territories in patients with migraine, opens a new field of research. In conclusion the association between migraine and stroke remains an open question. Solving the above mentioned issues is fundamental to understand the epidemiologic, pathogenetic and clinical aspects of migraine-related stroke

Chiari type I malformation, syncope, headache, hypoglycemia and hepatic steatosis in an 8-year old girl: a causal association?

Chiari type I malformation (CMI) is a congenital hindbrain anomaly characterized by downward displacement of the cerebellar tonsils through the foramen magnum. Chiari type I malformation often presents with a complex clinical picture and can be sporadic or linked to a variety of genetic conditions. We report on a girl in whom Chiari type I malformation was associated with hypoglycemia, headache, vertigo, syncope and hepatic steatosis. We hypothesize that these symptoms are primarily a consequence of Chiari type I malformation

Clinical and Pharmacological Aspects of Inflammatory Demyelinating Diseases in Childhood: An Update

Inflammatory demyelinating diseases comprise a spectrum of disorders affecting the myelin of the central and peripheral nervous system. These diseases can usually be differentiated on the basis of clinical, radiological, laboratory and pathological findings

Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations

Recent evidence indicates synaptic dysfunction as an early mechanism affected in neuroinflammatory diseases, such as multiple sclerosis, which are characterized by chronic microglia activation. However, the mode(s) of action of reactive microglia in causing synaptic defects are not fully understood. In this study, we show that inflammatory microglia produce extracellular vesicles (EVs) which are enriched in a set of miRNAs that regulate the expression of key synaptic proteins. Among them, miR-146a-5p, a microglia-specific miRNA not present in hippocampal neurons, controls the expression of presynaptic synaptotagmin1 (Syt1) and postsynaptic neuroligin1 (Nlg1), an adhesion protein which play a crucial role in dendritic spine formation and synaptic stability. Using a Renilla-based sensor, we provide formal proof that inflammatory EVs transfer their miR-146a-5p cargo to neuron. By western blot and immunofluorescence analysis we show that vesicular miR-146a-5p suppresses Syt1 and Nlg1 expression in receiving neurons. Microglia-to-neuron miR-146a-5p transfer and Syt1 and Nlg1 downregulation do not occur when EV\ue2\u80\u93neuron contact is inhibited by cloaking vesicular phosphatidylserine residues and when neurons are exposed to EVs either depleted of miR-146a-5p, produced by pro-regenerative microglia, or storing inactive miR-146a-5p, produced by cells transfected with an anti-miR-146a-5p. Morphological analysis reveals that prolonged exposure to inflammatory EVs leads to significant decrease in dendritic spine density in hippocampal neurons in vivo and in primary culture, which is rescued in vitro by transfection of a miR-insensitive Nlg1 form. Dendritic spine loss is accompanied by a decrease in the density and strength of excitatory synapses, as indicated by reduced mEPSC frequency and amplitude. These findings link inflammatory microglia and enhanced EV production to loss of excitatory synapses, uncovering a previously unrecognized role for microglia-enriched miRNAs, released in association to EVs, in silencing of key synaptic genes

Identification of Misfolded Proteins in Body Fluids for the Diagnosis of Prion Diseases

Transmissible spongiform encephalopathy (TSE) or prion diseases are fatal rare neurodegenerative disorders affecting man and animals and caused by a transmissible infectious agent. TSE diseases are characterized by spongiform brain lesions with neuronal loss and the abnormal deposition in the CNS, and to less extent in other tissues, of an insoluble and protease resistant form of the cellular prion protein (PrPC), named PrPTSE. In man, TSE diseases affect usually people over 60 years of age with no evident disease-associated risk factors. In some cases, however, TSE diseases are unequivocally linked to infectious episodes related to the use of prion-contaminated medicines, medical devices, or meat products as in the variant Creutzfeldt-Jakob disease (CJD). Clinical signs occur months or years after infection, and during this silent period PrPTSE, the only reliable marker of infection, is not easily measurable in blood or other accessible tissues or body fluids causing public health concerns. To overcome the limit of PrPTSE detection, several highly sensitive assays have been developed, but attempts to apply these techniques to blood of infected hosts have been unsuccessful or not yet validated. An update on the latest advances for the detection of misfolded prion protein in body fluids is provided

Feline cutaneous neuroendocrine carcinoma (Merkel cell tumour): clinical and pathological findings

A case of a feline Merkel cell tumour is described. An 8-year-old, female cat developed a round, alopecic, reddish mass on the nose. Wide excisional surgery was performed with cartilage resection. Histologically the mass was composed of solid islands of mostly basophilic densely packed cells with a scant cytoplasm, which was suggestive of a neuroendocrine origin. Results of immunohistochemical studies using antibodies against neurone-specific enolase, chromogranin, synaptophysin and pan-cytokeratin allowed classification of the lesion as a Merkel cell tumour. Ultrastructurally, dense core granules were identified in the cytoplasm. In a 2-year follow-up no relapses or metastases were observed. The clinical course recorded is in contrast with the malignant nature of a Merkel cell tumour recently described in a cat and of the human Merkel cell tumour, but is similar to the course of the canine Merkel cell tumour which is often benign. Early diagnosis along with the use of wide surgical excision might be considered an important factor in preventing relapse of this tumour

MTHFR homozygous mutation and additional risk factors for cerebral infarction in a large Italian family.

Several cases with cerebral infarctions associated with the C677T mutation in the methylenetetrahydrofolate reductase gene (MTHFR) have been reported. Given the large number of asymptomatic individuals with the MTHFR mutation, additional risk factors for cerebral infarction should be considered. This study describes a large family with the MTHFR mutation and a combination of heterozygous factor V Leiden mutations and different additional exogenous and endogenous thrombogenic risk factors. Psychomotor retardation and a left fronto-insular infarct associated with the MTHFR mutation together with diminished factor VII and low level of protein C was documented in the first patient. In the second patient, generalized epilepsy and a malacic area in the right nucleus lenticularis was associated with the MTHFR mutation and a low level of protein C. In the third patient, right hemiparesis and a left fronto-temporal porencephalic cyst were documented, together with the MTHFR mutation and hyperhomocysteinemia. An extensive search of additional circumstantial and genetic thrombogenic risk factors should be useful for prophylaxis and prognosis of infants with cerebral infarctions associated with the MTHFR mutation and of their related family members