Showing papers in "Neurological Sciences in 2006"

Pain-autonomic interactions.

Abstract: There are extensive interactions between the neural structures involved in pain sensation and autonomic control. The insular and anterior cingulate cortices, amygdala, hypothalamus, periaqueductal grey, parabrachial nucleus, nucleus of the solitary tract, ventrolateral medulla and raphe nuclei receive converging nociceptive and visceral inputs from the spinal and trigeminal dorsal horns and initiate arousal, affective, autonomic, motor and pain modulatory responses to painful stimuli. This review will focus on some central pain-autonomic interactions potentially relevant for the pathophysiology of primary headache.

Clinical and molecular diagnosis of cerebrotendinous xanthomatosis with a review of the mutations in the CYP27A1 gene

Abstract: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disease due to defective activity of the mitochondrial enzyme sterol 27-hydroxylase. In 1991, sterol 27-hydroxylase gene (CYP27A1) was localised on the long arm of chromosome 2 [1]. Clinical characteristics of CTX are diarrhoea, cataracts, tendon xanthomas and neurological manifestations including dementia, psychiatric disturbances, pyramidal and/or cerebellar signs, and seizures. More than 300 patients with CTX have been reported to date worldwide and about 50 different mutations identified in the CYP27A1 gene. Almost all mutations lead to the absence or inactive form of the sterol 27-hydroxylase. In this review, according with the aims of this section of the journal, we describe the different pathogenetic mutations in the CYP27A1 gene and the main clinical and pathogenetic aspects that may help clinical neurologists in the diagnosis of CTX.

The neuroprotective effect of inflammation: Implications for the therapy of multiple sclerosis.

Abstract: Autoreactive T cells are a regular component of the healthy immune system. It has been proposed that some of these autoreactive T cells even might have a protective function. Recent studies support this notion by demonstrating that: a) myelin-autoreactive T cells show neuroprotective effects in vivo, and b) activated antigen-specific human T cells and other immune cells produce bioactive brain-derived neurotrophic factor (BDNF) and other neurotrophic factors in vitro. Furthermore, BDNF is expressed in different types of inflammatory cells in brain lesions of patients with acute disseminated leukoencephalopathy or multiple sclerosis. It seems plausible that the immune cell-mediated import of BDNF and other neurotrophic factors into the central nervous system has functional consequences and implications for the therapy of multiple sclerosis and other neuroimmunological diseases.

Fertility in patients with multiple sclerosis: current knowledge and future perspectives.

Abstract: The issue of fertility in patients with multiple sclerosis (MS) has not been exhaustively studied. Epidemiological data have suggested that spontaneous fecundity might be reduced; several endocrine and sexual disturbances potentially interfering with reproduction have been evidenced in MS patients of both sexes. Moreover, some medical treatments used in MS (e. g., mitoxantrone, cyclophosphamide) may exert detrimental effects on spermatozoa as well as on oocytes, leading to early impairment of fertility. This review illustrates the factors potentially interfering with fertility in MS and discusses the therapeutic tools that may be used to promote fertility in these patients. The safety of hormonal therapies in MS is also examined. The current applications of assisted reproductive technology (ART) are discussed, including in vitro fertilisation (IVF) techniques. Currently available methods to preserve fertility in patients that undergo cytotoxic treatments by means of sperm/oocyte cryostorage or by ovarian fragment cryopreservation and autografting are considered.

Cerebral cavernomas and seizures: a retrospective study on 163 patients who underwent pure lesionectomy.

Abstract: The objective was to evaluate the outcome of microsurgical "pure" lesionectomy in patients with supratentorial cavernous angiomas presenting with seizures. For this retrospective study 163 patients with cavernoma-related epileptic seizures were selected. They all underwent surgery in a single institution between 1988 and 2003. A microsurgical frame/frameless guided minimally invasive transulcal "pure" lesionectomy was performed. The haemosiderin stained gliotic brain parenchyma that was usually found surrounding the lesion was not removed. Among the 99 patients with epilepsy and longer clinical history, 68 (68.7%) were found completely to be seizure-free, 10 (10.1%) presented sporadic and less frequent seizures and 17 (17.1%) remained unchanged. Sixty-three out of 64 (98.4%) patients who experienced only single or sporadic seizures were found to be completely seizure-free after surgery. Five patients were lost at follow-up (mean 48 months, range 0.5-14 years). Long-term morbidity was 1.8%. Mortality was null. No haemorrhagic episodes were observed during follow-up. Pure lesionectomy prevents bleeding and development of epilepsy in patients that receive early surgery after the epileptic onset. In most of the epileptic patients with a good concordance between the electroclinical data and the location of the angioma, good results can be achieved by this kind of surgery so that more invasive and costly studies to find and remove the epileptogenic cerebral parenchyma seem justified only after lesionectomy fails.

Increased intrathecal TGF-β1, but not IL-12, IFN-γ and IL-10 levels in Alzheimer’s disease patients

Abstract: An inflammatory response has been hypothesised to be involved in the pathogenesis of primary dementias, above all Alzheimer’s disease (AD). This study was aimed at evaluating interleukin (IL)-12 and a panel of related cytokine levels in paired CSF and sera of demented patients. IL-12 (p70 heterodimer and total IL-12 p40 chain), interferon (IFN)-γ, IL-10 and transforming growth factor (TGF)-β1 levels were measured in 30 patients with probable Alzheimer’s disease (PrAD), 57 patients with other dementing disorders, including probable vascular dementia (PrVD), Parkinson’s disease (PD) and normal pressure hydrocephalus (NPH), and 25 cognitively normal control subjects. In the presence of unchanged concentrations of IL-12, IFN-γ and IL-10, the mean CSF level of TGF-β1 and the correspondent TGF-β1 index, but not the serum level, were significantly increased in PrAD compared to controls and PrVD, whereas no difference was found vs. NPH and PD. Our results support the pathophysiological role of TGF-β1 system in AD.

From spreading depression to the trigeminovascular system.

Abstract: Migraine headaches have a complex pathophysiology; both vascular and neuronal mechanisms have been proposed. One possible scenario begins with brain-initiated events evolving to cortical spreading depression (CSD), which in turn activates the trigeminal nerve to cause headaches. Experimental evidence supports a relationship between CSD as a cause of migraine aura as well as CSD as a cause of trigeminal activation. Susceptibility to CSD and to migraine appears to be genetically determined. In some migraine subtypes, genes controlling translocation of calcium, sodium and potassium have been implicated, perhaps altering the susceptibility to CSD. This chapter briefly reviews current knowledge pertaining to migraine pathophysiology with emphasis on current notions linking disturbances in ion flux to the genesis of headache.

Inflammation and excitotoxicity: role in migraine pathogenesis.

Abstract: The pathogenesis of migraine is still unclear, but much evidence suggests a role of inflammation in pain generation. Calcitonin gene related peptide, nitric oxide and cytokines are all molecules shown to be involved both in animal and human studies. The glutamatergic system is also described as a possible mechanism leading to neuronal hyperexcitability and cortical spreading depression (CSD). Excitotoxic neural death, due to excessive release of the amino acid in the extracellular space, may represent a consequence of protracted CSD and oligaemia and may be involved in migrainous infarction and aspecific lesions seen on T2-weighted NMR imaging.

Neurophysiological features of the migrainous brain.

Abstract: Migraine is a disorder in which central nervous system (CNS) dysfunction might play a pivotal role. As there are no consistent structural disturbances, clinical neurophysiology methods seem particularly suited to study its pathophysiology. This chapter will focus on a review of neurophysiological studies that have provided an insight into migraine pathogenesis. The results are in part contradictory, which may be due to the methodology, patient selection or timing of study. Nonetheless, quantitative electroencephalography and magnetoencephalography recordings during migraine attacks provide strong, though indirect, evidence favouring the occurrence of spreading cortical depression during attacks of migraine with, and possibly without, aura. Evoked cortical potential and nociceptive blink reflex studies demonstrate that lack of habituation during repetitive stimulation is a reproducible CNS dysfunction interictally in both migraine with and without aura. Transcranial magnetic stimulations show excitability changes of the visual cortex. The interictal migrainous CNS dysfunction is likely to play a role in migraine pathogenesis, has a familial character and undergoes periodic modulations with quasi-normalisation just before, during an attack and after treatment with certain prophylactic agents. In addition, neurophysiological methods have revealed subclinical abnormalities of cerebellar function and neuromuscular transmission, which may improve phenotyping of migraineurs for genetic and therapeutic studies.

Predictive variables on disability and quality of life in stroke outpatients undergoing rehabilitation.

Abstract: The purposes of this study were: (1) to evaluate the relationship between disability and Quality of Life (QoL) in stroke outpatients undergoing rehabilitation and (2) to determine whether and how demographic and social features of the patient, duration of disease and concomitant diseases influence the disability and QoL of the stroke outpatients. We performed a prospective study using several conventional disability measurements (Barthel Index, Functional Independence Measure, Modified Rankin Scale and Deambulation Index) and a validated patient-oriented measurement of QoL (SF-36). Sixty-eight outpatients were evaluated consecutively. As expected, all disability measurements were related to Physical Function: patients with higher disability, according to the physician’s perspective, complained of higher deterioration of physical performance. Unexpectedly, patients with higher disability from the physician’s point of view perceive that they were not able to do some daily activities not only because of physical problems but also because of emotional problems, and complained of higher deterioration of mental health. Multivariate analysis showed that higher disability is associated with higher age, depression and lower educational level. Physical Composite Score appeared to be deteriorated in patients with lower educational level who lived with family; on the contrary, Mental Composite Score appeared deteriorated in patients with higher educational level who lived alone. The current study provides interesting data about the relationship, not always expected, between disability and QoL for stroke patients and about the influence of patients’ characteristics on disability and QoL. Our results showed that in a rehabilitation programme we should consider not only disability assessment but also QoL, which is more relevant for the patient.

The end of the central dogma of neurobiology: stem cells and neurogenesis in adult CNS.

Abstract: Until the 1990s, neurologists were practising their profession under the doctrine established in the late 19th to early 20th century by the prominent histologist Ramon y Cajal: "Once the development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably. In the adult centers, the nerve paths are something fixed, ended, and immutable. Everything may die, nothing may be regenerated. It is for the science of the future to change, if possible, this harsh decree." Similarly, Giulio Bizzozero, the most prominent Italian histologist and mentor of Camillo Golgi, classified the tissues of the human body into "labile, stable and perennial". Among the latter were the nerve cells, believed to be unable to proliferate in the postnatal brain. This classification was taught until a few years ago to generations of medical students and biologists all over the world. We have investigated the historical, methodological and technical reasons why this "central dogma of neurology", so influential in clinical and experimental neurology, has lasted so long. We examined how this dogma was broken and who contributed, and the difficulties encountered by the "heretical" researchers who contributed to this goal, especially between the 1960s and the early 1990s, when at last neurogenesis in the adult brain could no longer be denied. Finally, we propose that the understanding of the mechanisms underlying various neurological diseases and the interpretations of clinical syndromes, as well as the design of new therapies, are being revolutionised by the breaking of this dogma and the discovery of the presence of neural stem cells in the adult brain.

Novel therapeutic targets.

Abstract: The need for novel therapeutic strategies for the treatment of migraine and other primary headaches is well recognised. Although the underlying mechanism(s) and the molecular targets that should be tackled by novel medicines are still uncertain, significant improvements have been made in the last decade in the treatment of migraine. Strong evidence in experimental animal models and clinical investigation focus on drugs that limit the phenomena promoted by activation of neurons of the trigeminal ganglion at the level of both their central and peripheral perivascular endings. Identification of compounds that abort the migraine attack by precisely targeting different mechanisms should also help to recompose the puzzle of migraine pathogenesis.

PRES: posterior or potentially reversible encephalopathy syndrome?

Abstract: Posterior reversible encephalopathy syndrome (PRES) is an acronym that identifies a new clinico-neuroradiologic entity occurring in association with different conditions. We report a patient with eclamptic encephalopathy whose clinico-radiological picture normalised after prompt treatment. We suggest defining this condition as potentially RES, to emphasise that reversibility is not spontaneous but is usually related to an adequate treatment, and that the posterior localisation of the lesions, even if constant, may not represent the most relevant finding in some patients.

High plasma creatine kinase: review of the literature and proposal for a diagnostic algorithm.

Abstract: The condition of persistently high plasma CK levels is frequently encountered in asymptomatic patients with normal neurological examination. This condition may be the unique manifestation of several neuromuscular disorders, whose diagnosis is now possible using new diagnostic techniques. However, even if these patients are intensely investigated, specific diagnoses are not always forthcoming. Because of the lack of a widely accepted diagnostic protocol, hyperCKaemia in asymptomatic subjects is a potentially difficult clinical problem. In this paper we review the literature on conditions associated with variations in plasma CK levels and the literature on investigations carried out in asymptomatic persons with high CK to identify neuromuscular diseases. In the light of these data, and the deliberations of a working group of the Italian Association of Myology, we propose a diagnostic algorithm to guide the diagnostic work-up of persons presenting with persistently high levels of plasma CK. This algorithm has been discussed and approved by the Committee of the Italian Association of Myology.

Guillain-Barré syndrome.

Abstract: Guillain-Barre syndrome (GBS) is an autoimmune acute peripheral neuropathy. Frequently a flu-like episode or a gastroenteritis precede GBS, and the cross-reactivity between microbial and neural antigens partly explains the pathophysiology of the disease and the possible detection of antiganglioside antibodies. The weakness reaches its nadir in 2-4 weeks: the patients may be chair- or bed-bound, may need artificial ventilation and frequently experience dysautonomic dysfunction; 5-15% of the patients die and more patients are left with a disabling motor deficit and/or fatigue. Electrophysiology and cerebrospinal fluid evaluation support the diagnosis. The treatment of GBS is multidisciplinary, and both plasma exchange and high dose immunoglobulin (IVIg) are effective in reducing both the severity of the disease and the residual deficits. Finally, steroids are not effective in GBS.

Medications for neuropathic pain: current trends

Abstract: Neuropathic pain is by definition a chronic pain condition that occurs and persists in a heterogeneous group of aetiologically different diseases characterised by a primary lesion or dysfunction of the peripheral or central nervous system. Neuropathic pain has an important prevalence in the general population, and a severe impact on quality of life and mood of affected patients. Therapy is based on tricyclic antidepressants and antiepileptic drugs, the most frequently studied drug classes. Opioids and analgesics are a second-line choice. Topical medications could be useful in several pain situations.

Arachnoid cyst with intracystic haemorrhage and subdural haematoma: case report and literature review.

Abstract: Arachnoid cysts (AC) are usually asymptomatic. However, very rarely they can become symptomatic due to cyst enlargement or haemorrhage, often after head trauma. In such cases bleeding is often confined to the subdural space, but intracystic haemorrhage has rarely been observed. We report a case of a child who had intracranial hypertension syndrome due to a right middle cranial fossa AC with intracystic bleeding and subdural haematoma.

Iatrogenic intracranial pseudoaneurysms: Neuroradiological and therapeutical considerations, including endovascular options

Abstract: Intracranial pseudoaneurysms represent a potentially fatal complication of intracranial surgery. Our purpose is to describe their neuroradiological characteristics, prognostic features and possible treatment. Eight cases of postsurgical intracranial pseudoaneurysms have been observed at our institution since 1988. Four were observed following transsphenoidal (TS) surgery and four after pterional craniotomies. Two types of iatrogenic pseudoaneurysms were observed: “fusiform”, probably due to weakening of the adventitia during surgical peeling of the tumour from the artery (three cases) and “saccular”, occurring after a more focal or complete laceration of the vessel (five cases), more often after TS surgery. A thorough preoperative neuroradiological examination may identify anatomical conditions at risk for development of this severe complication. Postoperative neuroradiological follow-up is mandatory in cases in which unusual bleeding has occurred during the perioperative period, but absence of bleeding does not exclude the possible devel opment of a pseudoaneurysm. Endovascular treatment of pseudoaneurysms represents a safe and durable procedure, specifically in those cases in which damage to the carotid siphon occurred during TS surgery.

Pathophysiological mechanisms of neuropathic pain.

Abstract: Neuropathic pain is a common problem in clinical practice and one that adversely affects patients’ quality of life. Converging evidence from animal and human studies demonstrates that neuropathic pain arises from a lesion in the somatosensory system. Injured peripheral nerve fibers give rise to an intense and prolonged ectopic input to the CNS and, in some cases, also to secondary changes in dorsal horn neuronal excitability. Convincing evidence now suggests that classifying neuropathic pain according to a mechanism-based rather than an etiology-based approach might help in targeting therapy to the individual patient and would be useful in testing new drugs. This article summarizes our current understanding of the peripheral and central pathophysiological mechanisms underlying neuropathic pain and focuses on how symptoms translate into mechanisms.

A self-administered questionnaire of ulnar neuropathy at the elbow.

Abstract: We report a new self-administered questionnaire for assessment of symptom severity of ulnar neuropathy at the elbow (UNE). The new UNE and Levine's questionnaires were administered to a sample of UNE subjects and for comparison also to a sample of subjects with carpal tunnel syndrome (CTS). We enrolled 89 consecutive patients (32 women, 57 men, mean age 52.3 years) with UNE and 203 consecutive patients (157 women and 46 men, mean age 53.7 years) with CTS. The protocol of the study consisted in self-administration of the new UNE and Levine's questionnaires, as well as scoring of clinical and electrophysiological severity of entrapment syndromes with ordinal scales. The UNE questionnaire (UNEQ) includes nine questions and considers numbness and tingling in the fourth and fifth fingers, elbow pain and modification of pain and paraesthesia with elbow position. A score from 1 (absence of symptom) to 5 (most severe) is assigned for each question. The overall score is calculated as the mean of the nine scores. Test-retest reliability, internal consistency and validity were assessed. Responsiveness was also tested in a sample of patients undergoing conservative treatment. The UNEQ was reproducible. Spearman's correlation coefficient between scores at successive observations (test-retest reliability), assessed in the first 44 patients, was 0.97 and Cohen coefficients kappa for single items were between 0.64 and 0.81. Internal consistency was high: Cronbach's alpha, which summarises interitem correlations among all items of UNEQ, was 0.87. Validity was demonstrated by a direct correlation with UNE clinical and electrophysiological severity scores (0.65 and 0.35). On the contrary, Spearman's correlation coefficients between UNEQ and clinical and electrophysiological CTS severity scores were low (0.11 and 0.02, respectively). Responsiveness was calculated at 6-8 months follow-up in 25 cases. The effect size was 0.46. The Wilcoxon rank-test showed significant improvement between basal and follow-up UNEQ scores (Z=-2.39, p=0.017), but not Boston Questionnaire scores. There was also significant correlation between UNEQ changes and an arbitrary scale of patient satisfaction at follow-up (r=0.85, p<0.001). The UNEQ is reproducible, internally consistent and valid. Although further studies are required to test its responsiveness to clinical changes, UNEQ may be also considered responsive. UNEQ can be used to measure subjective discomfort in UNE patients.

Efficacy and tolerability of almotriptan versus zolmitriptan for the acute treatment of menstrual migraine.

Abstract: Menstrual migraine (MM) attacks are a challenge for the headache specialist, because they are particularly difficult to treat. Almotriptan is a second-generation triptan successfully used for the acute treatment of migraine. No data on the efficacy and safety of almotriptan in MM treatment have been published previously. The objective was to evaluate the efficacy and tolerability of almotriptan in the symptomatic treatment of MM attacks and to compare these parameters to those obtained with zolmitriptan, another second-generation triptan. Data from a multicentre, multinational, randomised, double-blind, parallel clinical trial, conducted at 118 centres in 9 European countries, to evaluate the efficacy and tolerability of almotriptan 12.5 mg vs. zolmitriptan 2.5 mg in the acute treatment of migraine were analysed retrospectively. Of the 1061 patients included, 902 were women and 255 of these treated a MM attack: 136 with almotriptan and 119 with zolmitriptan. No significant difference between the two treatments was found. Two hours after dosing, 67.9% of almotriptan-treated and 68.6% of zolmitriptan-treated patients had obtained pain relief; while 44.9% and 41.2%, respectively, were pain free. Recurrence rates 2–24 h after dosing were 32.8% for almotriptan and 34.7% for zolmitriptan. Adverse events in the 24 h after dosing were reported by 19.8% of those taking almotriptan and 23.1% of those taking zolmitriptan. In conclusion, almotriptan is effective and safe in the treatment of MM attacks.

Neuroimaging and pain: a window on the autonomic nervous system.

Abstract: Pain is one of the most common experiences of humans. Neuroimaging techniques can visualize the main brain areas involved in pain modulation, the pain matrix. It is noteworthy that many of the brain areas forming the pain matrix are also involved in modulating autonomic nervous system (ANS) activity that in turn plays a major role in determining the best adaptive response to the pain experience. The tight connection between the pain system and ANS is also evident from neuroanatomical studies indicating that the lamina 1 neurons receive both painful and visceral stimuli from all visceral organs giving rise to the spinothalamocortical pathway concerned with conveying interoceptive information to central structures. The resulting interoceptive stream projects to the viscerosensory cortex in the mid-insula and onto the right anterior insula and orbitofrontal cortices. Right anterior insula activation is involved in the sympathetic arousal associated with mental tasks. This brain region receives numerous other inputs including pain and painful stimuli are conveyed somatotopically to both insulae. A similar somatotopic organization of painful stimuli has also been shown in the basal ganglia involved in cognitive, affective, motor and autonomic states. This highly specialized organization of nociceptive information in these brain areas may subserve a number of functions, particularly of coupling pain with the most appropriate autonomic states and affective/emotional states. The anterior cingulated cortex, another brain area playing a crucial role in nociception, is also directly involved in the control of autonomic functions such as arousal during volitional behaviour, including effortful cognitive processing. It is evident that the nociceptive system and ANS closely interact in many processes involved in maintaining internal homeostatis and in order to give the most appropriate biological substrate for cognitive, affective and emotional states.

Mismatch in how oestrogen modulates molecular and neuronal function may explain menstrual migraine.

Abstract: This paper is designed to provide concepts and stimulate directions for further investigation of menstrual migraine. On the basis of experimental studies and literature review, we propose that abnormalities in how estrogen modulates neuronal function in migraine are due to a mismatch between its gene-regulation and membrane effects. In the interictal phase when estrogen levels peak, increased neuronal excitability is balanced by homeostatic gene regulation in brain cortex, and nociceptive systems. When levels fall at menses, mismatch in homeostatic gene regulation by estrogen unmasks non-nuclear mitogen-activated hyperexcitability of cell membranes, sensitizing neurons to triggers that activate migraine attacks. At the trough of estrogen levels, the down-regulating effect on inflammatory genes is lost and peptide modulated central sensitization is increased as is pain and disability of the migraine attack.

Sleep-related breathing disorders and headache.

Abstract: Obtructive sleep apnoea syndrome (OSAS) is a common disorder in the general population with an estimated prevalence in an adult population of 2% in women and 4% in men. Although several studies have suggested that headaches, particularly morning headaches, are more common in patients with OSAS than in normal subjects, others have yielded contradictory findings. When the sleep-related breathing disorder was treated with success, the headache generally disappeared, supporting a causal role of the sleep disorder for headache. Several hypotheses have been proposed to explain the relationship between OSAS and the occurrence of headache, particularly on awakening. Night-time fluctuations of oxygen saturation during the night with hypercapnia, vasodilatation, increased intracranial pressure and impaired sleep quality are all considered contributing factors. However the exact mechanisms of headache pathogenesis and the relationship between OSAS, headache and morning headaches in particular remain controversial.

Hypothalamus, sleep and headaches.

Abstract: The hypothalamus is a key neural region in the regulation of sleep, its anterior part implicated in sleep facilitation, while the posterior hypothalamus acts in a balanced way to maintain wakefulness. The hypothalamus forms part of the so-called central autonomic network, regulating body homeostasis and controlling pain. To this effect, it is strongly wired to more rostral and caudal areas, in particular the brainstem periaqueductal grey, the locus coeruleus and the median raphe nuclei, all involved in sleep mechanisms and also in the descending control of pain perception. The hypothalamus, especially its posterior regions, becomes activated during attacks of the socalled trigeminal autonomic cephalalgias (TACs), while brainstem, especially dorsal pontine, activity shows up during migraine attacks. The hypothalamus and interconnected brainstem areas likely represent the neural sites responsible for the chronobiological features of some headaches, in particular the sleep-related attacks typical of the TACs, migraines and the hypnic headaches.

Psychiatric comorbidity and headache: clinical and therapeutical aspects.

Abstract: General population studies suggest a non-casual association (comorbidity) between migraine, major depression and anxiety disorders (panic attack disorder, obsessive-compulsive disorder, generalised anxiety disorder). The risk of developing affective and anxiety disorders is not increased uniformly in the different migraine subtypes, but it is more elevated in migraine with aura patients. The relationship between migraine and depression is "bi-directional" (i. e., migraineurs have a more than three-fold risk of developing depression compared with non-migraine patients, while depression patients that have never suffered from migraine before have a more than three-fold risk of developing migraine compared with nondepressed patients) and specific (i. e., the presence of migraine or severe non-migraine headache increases a patient's risk of developing depression or panic attack disorder, whereas the presence of depression or panic attack disorder is associated with a greater risk of developing migraine, but not severe non-migraine headache). Comorbidity with psychiatric disorders has also been described for chronic tension-type headache and for chronic daily headache, although these findings are based only on clinical population data.

The spectrum of mutations for the diagnosis of vanishing white matter disease.

Abstract: Vanishing white matter disease (VWM; MIM #603896), also known as childhood ataxia with central nervous system hypomyelination (CACH) syndrome, is an autosomal recessive transmitted leukoencephalopathy related to mutations in each of the 5 genes (EIF2B1, EIF2B2, EIF2B3, EIF2B4 and EIF2B5) encoding for the 5 subunits of eukaryotic translation initiation factor 2B (eIF2B), essential for protein synthesis. VWM is characterised by ataxia, spasticity, variable optic atrophy and intermittent episodes of acute regression of clinical and neurological status. Another key step in diagnosis, besides clinical picture and gene sequencing, is magnetic resonance imaging (MRI), which typically shows a progressive rarefaction of the brain white matter, and its replacement by cerebrospinal fluid (CSF). In the present paper we summarise the up-to-date knowledge about VWM and include the full list of known mutations.

Neurobiological bases of rehabilitation.

Abstract: The adult brain maintains the ability to reorganise throughout life. Motor cortical representations can reorganise rapidly in response to different stimuli. Important mechanisms for mediating reorganisation in the cerebral cortex involve the unmasking of existing, but latent, horizontal connections and modulation of GABAergic inhibition and synaptic efficacy. Interfering with these mechanisms can either block or enhance reorganisational processes. Following injury to the motor cortex alterations of the neurotransmitter system regulation, recruitment of additional undamaged brain areas even remote from the injury, and anatomical alterations such as axonal sprouting and synaptogenesis in the brain tissue surrounding the lesion or in the homotopic motor area of the non-affected hemisphere occur. The understanding of cortical reorganisation may enable us to apply principles of plasticity to the rehabilitation of patients after brain injury.

Hypnic headache: an update.

Abstract: Hypnic headache (HH) is a rare sleep-associated primary headache disorder, usually affecting aged people, first described by Raskin in 1988. The headache attacks, single or multiple in one night, occur exclusively during sleep and tend to present at a consistent time each night, sometimes during a dream. Compared to the original description, newly reported cases have expanded the clinical spectrum of the disorder to include unilateral forms (about 40%, half of which are side-locked), forms with a longer duration (up to 3 h) and cases with onset in juvenile/adult age. The male predominance found in Raskin’s series has not been confirmed by subsequent observations. To date the reported F/M ratio is 1.7/1. Pain is of severe intensity in less then one-third of cases and mild-moderate in about two-thirds. The location of pain is fronto-temporal in over 40% of cases; headache is throbbing in 38% of cases, dull in 57% and stabbing in less than 5%. Nausea is reported in 19% of cases; photophobia, phonophobia or both are present in 6.8%. Mild autonomic signs (lacrimation, nasal congestion, ptosis) may rarely be present. In 2004, HH was included in Group 4 of the International Classification of Headache Disorders—II (Other primary headaches). Sufficient evidence, mainly from polysomnographic studies, indicates that HH is a primary rapid eye movement (REM) sleep-related headache disorder of chronobiological origin. Lithium, melatonin, indomethacin and caffeine at bedtime are among the most effective therapeutic options. The pathophysiology of HH is still unclear. Available data allow speculation that, in predisposed subjects, an age-related impairment of suprachiasmatic nucleus could cyclically activate a disnociceptive mechanism leading to both a sudden awakening and headache. The mechanism may be precipitated by neurophysiologic events such as the strong reduction of firing occurring in the dorsal raphe nucleus during a REM sleep phase.

Chromatic pattern-reversal electroretinograms (ChPERGs) are spared in multiple system atrophy compared with Parkinson’s disease

Abstract: Idiopathic Parkinson’s disease (IPD) patients have abnormal visual evoked potentials (VEPs) and pattern electroretinograms (PERGs), attributed to dopaminergic transmission deficiency in visual pathway, probably the retina. VEP abnormalities are not reported in multiple system atrophy (MSA). The aim of this study was to investigate and compare chromatic (Ch) red-green (R-G) and blue-yellow (B-Y), and luminance yellow-black (Y-Bk) PERGs in patients with MSA and IPD. We investigated 6 MSA patients (mean age: 62±7.4 years) not undergoing any pharmacological treatment, as well as 12 early IPD patients (mean age: 60.1±8.3 years) and 12 age-matched normal observers. ChPERGs were recorded monocularly in response to full-field equiluminant R-G, B-Y and Y-Bk horizontal gratings. In MSA only responses to R-G stimuli showed minimal insignificant changes (slight but not significant amplitude reduction without any significant latency delay); no significant abnormality was detected for B-Y and luminance Y-Bk stimuli. By contrast, in IPD all responses were reduced in amplitude and delayed in latency, above all for B-Y stimuli. Present data indicate that both chromatic and achromatic PERGs are virtually unaffected in MSA, whereas in early IPD they are clearly impaired, suggesting different pathogenic retinal mechanisms and a useful simple tool for distinguishing MSA from IPD.