mercoledì 31 luglio 2013
domenica 28 luglio 2013
The sign, which was termed the “poly-hill sign” was considered positive when certain features were present. Over the superolateral border of neck, shoulder, and arm, from medial to lateral side, the following
(1) depression due to wasting of trapezius,
(2) a bulge due to jutting of the superior angle of the scapula,
(3) second depression from the wasted trapezius,
(4) a bulge due to unusual bony prominence of the inferolaterally displaced acromio-clavicular joint,
(5) a depression due to wasting of the proximal one-fourth of the deltoid muscle fibers originating from the acromion processes,
(6) a bulge due to a slightly enlarged (in early stage) or relatively preserved (in late stage) distal threefourths of the deltoid muscle,
(7) a depression due to wasted biceps muscle
(8) a bulge due to preserved bulk or hypertrophy of brachioradialis or extensor digitorum communis muscle.
sabato 27 luglio 2013
Altered splicing of ATP6AP2 causes X-linked parkinsonism with spasticity (XPDS)
We aimed to identify the target antigens or combined central and peripheral demyelination (CCPD).
We screened target antigens by immunohistochemistry and immunoblotting using peripheral nerve tissues to identify target antigens recognized by serum antibodies from selected CCPD and chronic inflammatory demyelinatingpolyradiculoneuropathy (CIDP) cases. We then measured the level of antibody to the relevant antigen in 7 patients with CCPD, 16 patients with CIDP, 20 patients with multiple sclerosis, 20 patients with Guillain-Barré syndrome, 21 patients with other neuropathies, and 23 healthy controls (HC) by ELISA and cell-based assays using HEK293 cells.
At the initial screening, sera from 2 patients with CCPD showed cross-like binding to sciatic nerve sections at fixed intervals, with nearly perfect colocalization with neurofascin immunostaining at the node and paranode. ELISA with recombinant neurofascin revealed significantly higher mean optical density values in the CCPD group than in other disease groups and HC. Anti-neurofascin antibody positivity rates were 86% in patients with CCPD, 10% in patients with multiple sclerosis, 25% in patients with CIDP, 15% in patients with Guillain-Barré syndrome, and 0% in patients with other neuropathies and HC. The cell-based assay detected serum anti-neurofascin antibody in 5 of 7 patients with CCPD; all others were negative. CSF samples examined from 2 patients with CCPD were both positive. In anti-neurofascin antibody-positiveCCPD patients, including those with a limited response to corticosteroids, IV immunoglobulin or plasma exchange alleviated the symptoms.
Anti-neurofascin antibody is frequently present in patients with CCPD. Recognition of this antibody may be important, because patients with CCPD who are antibody positive respond well to IV immunoglobulin or plasma exchange.
Neurology July 2013
martedì 23 luglio 2013
domenica 21 luglio 2013
Alzheimer's Association International Conference (AAIC) 2013. Poster P4-007. Presented July 12, 2013.
Alzheimer's disease is characterized by progressive decline in cognitive functioning, especially in memory but also executive functioning (including planning, attention and problem solving) and global cognition. Each person may experience Alzheimer's differently, and there are considerable differences in rates of decline between affected individuals.
"If we can understand more about the genetic basis of this variability in rate of decline, it could help illuminate the biological pathways involved in disease progression," said Richard Sherva, Ph.D., research assistant professor in the department of Biomedical Genetics at Boston University School of Medicine. "It also could inform the development of therapies to slow the progression of disease."
Sherva and colleagues are utilizing research funds awarded by the Alzheimer's Association to study the genetics of the rate of Alzheimer's-related cognitive decline in a large population from a completed clinical trial. By expanding their work into a multi-institutional consortium (known as Genetic Architecture of Rate of Alzheimer's Decline, or GENAROAD, led by Drs. Robert Green and Paul Crane), they have amassed a relatively large sample of Alzheimer's cases with the longitudinal data necessary to study the topic in depth.
At AAIC 2013, Sherva reported genome wide association studies (GWAS) from participants in multiple research studies including the Alzheimer's Disease Neuroimaging Initiative (n=301), National Alzheimer's Coordinating Centers (n=865), Religious Orders Study/Rush Memory and Aging Project (n=323), and AddNeuroMed study (n=123). The combined GWAS identified at least four genetic variants strongly associated with rate of decline in Alzheimer's, including SPON1, MANB4A, KCNJ14, MAP3K1 and HIBADH.
"We found that the genes that influence rate of decline are largely different that those that influence Alzheimer's risk in general but are genes involved in pathways related to Alzheimer's risk," Sherva said. "The most interesting gene we identified is called SPON1, which has functions related to beta-amyloid generation and also regulates brain cell connectivity."
In the past year, mutations in the PRRT2 gene have been identified in patients with paroxysmal kinesigenic dyskinesia and other paroxysmal disorders. We conducted a review of the literature on PRRT2 mutation-associated disorders. Our objectives were to describe the wide clinical spectrum associated with PRRT2 mutations, and to present the current hypotheses on the underlying pathophysiology.PRRT2 mutations are associated with a wide range of clinical syndromes: the various paroxysmal dyskinesias, infantile seizures, paroxysmal torticollis, migraine, hemiplegic migraine, episodic ataxia and even intellectual disability in the homozygous state. The PRRT2protein, through its interaction with SNAP-25, could play a role in synaptic regulation in the cortex and the basal ganglia. The pathogenesis may be caused by PRRT2 loss of function, which may induce synaptic deregulation and neuronal hyperexcitability. However, this does not explain the phenotypic variability, which is likely modulated by environmental factors, modifier genes or age-dependent expression. The clinical spectrum of PRRT2 mutations has expanded among paroxysmal disorders and beyond. Unraveling the molecular pathways linking the genetic defect to its clinical expression will be crucial for the diagnosis and treatment of these disorders.
giovedì 18 luglio 2013
martedì 16 luglio 2013
The cerebral cortex contains 2 types of neurons: principal (mostly pyramidal) neurons, which constitute approximately 80% of the total population, and local interneurons, which constitute approximately 20% of the total population, with some species variation. Pyramidal cells are excitatory glutamatergic neurons that participate in cortico-cortical connections or project to subcortical areas. Local interneurons utilize γ-aminobutyric acid (GABA) as their primary neurotransmitter and participate in local circuits in the cerebral cortex. Normal sensory perception, attention, and planning and execution of behaviors depend on interactions among canonical neocortical circuits involving excitatory and inhibitory neurons. Cortical interneurons have a fundamental role in shaping cortical circuits and controlling neocortical network interactions. These interneurons form functionally distinct networks that are temporally coordinated by electrical coupling via gap junctions, and establish GABAergic synapses not only with pyramidal neurons but also among each other. Via these interactions, GABAergic interneurons control the timing of pyramidal cell firing, generation of cortical rhythms, organization of sensory fields, and cortical plasticity. Impaired activity of neocortical inhibitory interneurons has been associated with several neurologic and psychiatric disorders, including epilepsy, mental retardation, schizophrenia, and autism. There are many comprehensive reviews on GABAergic interneuron heterogeneity, development, plasticity, function in shaping cortical activity, and involvement in disease.
Neurology. 2013 Jun 14. [Epub ahead of print]
To design and validate a clinical diagnostic guideline for aiding physicians in confirming or refuting suspected blepharospasm.
The guideline was developed and validated in a 3-step procedure: 1) identification of clinical items related to the phenomenology of blepharospasm, 2) assessment of the relevance of each item to the diagnosis of blepharospasm, and 3) evaluation of the reliability and diagnostic sensitivity/specificity of the selected clinical items.
Of 19 clinical items initially identified, 7 were admitted by content validity analysis to further assessment. Both neurologists and ophthalmologists achieved satisfactory interobserver agreement for all 7 items, including "involuntary eyelid narrowing/closure due to orbicularis oculi spasms," "bilateral spasms," "synchronous spasms," "stereotyped spasm pattern," "sensory trick," "inability to voluntarily suppress the spasms," and "blink count at rest." Each selected item yielded unsatisfactory accuracy in discriminating patients with blepharospasm from healthy subjects and patients with other eyelid disturbances. Combining the selected items, however, improved diagnostic sensitivity/specificity. The best combination, yielding 93% sensitivity and 90% specificity, was an algorithm starting with the item "stereotyped, bilateral, and synchronous orbicularis oculi spasms inducing eyelid narrowing/closure" and followed by recognition of "sensory trick" or, alternatively, "increased blinking." CONCLUSION: This study provides an accurate and valid clinical guideline for diagnosing blepharospasm. Use of this guideline would make it easier for providers to recognize dystonia in clinical and research settings
domenica 14 luglio 2013
sabato 13 luglio 2013
giovedì 11 luglio 2013
Cerebral hyperperfusion syndrome: a novel presentation of internal carotid artery dissection
Cervical artery dissection (CeAD) occurs preferentially in the middle-aged, and its annual incidence rate is 2.6 to 3.0 per 100,000. Manifestations of internal carotid artery dissection (ICAD) include ischemic stroke and TIA (>70% of patients), headache, neck pain, Horner syndrome, cranial nerve palsy, pulsatile tinnitus, and, rarely, subarachnoid hemorrhage. Cerebral hyperperfusion syndrome is known to occur after carotid artery revascularization procedures and it is thought to result from the combination of several factors that impair cerebral vascular autoregulatory mechanisms.
Neurology, July 3 2013