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Introduction: Transcranial magnetic stimulation (TMS) is one of the best methods to identify changes in the corticospinal tract. We used single-pulse TMS at the beginning of the disease and in the follow-up in a group of patients with amyotrophic lateral sclerosis (ALS)., Methods: We evaluated the corticospinal tract in the bulbar, upper, and lower regions in 55 patients with ALS, and we monitored them for a period of 24 months. Data were correlated with clinical scales., Results: An increase of central motor conduction time (CMCT) was the most sensitive marker of upper motor neuron involvement. The resting motor threshold, CMCT, and the central silent period increased linearly with disease duration and upper/lower motor neuron involvement., Discussion: Transcranial magnetic stimulation could be an essential neurophysiological technique in the early phase of ALS because it has been shown to be useful in detecting subclinical upper motor neuron involvement. Multiple evaluations of several regions increase TMS sensitivity., (© 2019 Wiley Periodicals, Inc.)

Mild traumatic brain injury (mTBI), particularly mild "blast type" injuries resulting from improvised exploding devices and many sport-caused injuries to the brain, result in long-term impairment of cognition and behavior. Our central hypothesis is that there are inflammatory consequences to mTBI that persist over time and, in part, are responsible for resultant pathogenesis and clinical outcomes. We used an adaptation (1 atmosphere pressure) of a well-characterized moderate-to-severe brain lateral fluid percussion (LFP) brain injury rat model. Our mild LFP injury resulted in acute increases in interleukin-1α/β and tumor necrosis factor alpha levels, macrophage/microglial and astrocytic activation, evidence of heightened cellular stress, and blood-brain barrier (BBB) dysfunction that were evident as early as 3-6 h postinjury. Both glial activation and BBB dysfunction persisted for 18 days postinjury.

In the spinal cord, neuron and glial cells actively interact and contribute to neurofunction. Surprisingly, both cell types have similar receptors, transporters and ion channels and also produce similar neurotransmitters and cytokines. The neuroanatomical and neurochemical similarities work synergistically to maintain physiological homeostasis in the normal spinal cord. However, in trauma or disease states, spinal glia become activated, dorsal horn neurons become hyperexcitable contributing to sensitized neuronal-glial circuits. The maladaptive spinal circuits directly affect synaptic excitability, including activation of intracellular downstream cascades that result in enhanced evoked and spontaneous activity in dorsal horn neurons with the result that abnormal pain syndromes develop. Recent literature reported that spinal cord injury produces glial activation in the dorsal horn; however, the majority of glial activation studies after SCI have focused on transient and/or acute time points, from a few hours to 1 month, and peri-lesion sites, a few millimeters rostral and caudal to the lesion site. In addition, thoracic spinal cord injury produces activation of astrocytes and microglia that contributes to dorsal horn neuronal hyperexcitability and central neuropathic pain in above-level, at-level and below-level segments remote from the lesion in the spinal cord. The cellular and molecular events of glial activation are not simple events, rather they are the consequence of a combination of several neurochemical and neurophysiological changes following SCI. The ionic imbalances, neuroinflammation and alterations of cell cycle proteins after SCI are predominant components for neuroanatomical and neurochemical changes that result in glial activation. More importantly, SCI induced release of glutamate, proinflammatory cytokines, ATP, reactive oxygen species (ROS) and neurotrophic factors trigger activation of postsynaptic neuron and glial cells via their own receptors and channels that, in turn, contribute to neuronal-neuronal and neuronal-glial interaction as well as microglia-astrocytic interactions. However, a systematic review of temporal and spatial glial activation following SCI has not been done. In this review, we describe time and regional dependence of glial activation and describe activation mechanisms in various SCI models in rats. These data are placed in the broader context of glial activation mechanisms and chronic pain states. Our work in the context of work by others in SCI models demonstrates that dysfunctional glia, a condition called "gliopathy", is a key contributor in the underlying cellular mechanisms contributing to neuropathic pain., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In the present study, we examined whether activation of p-38alpha MAPK modulates mechanical allodynia and neuronal hyperexcitability, and if propentofylline (PPF, a glial modulator) modulates specifically localized activated p-38alpha MAPK expression in caudal regions remote from a low thoracic hemisection injury in rats. T13 spinal hemisection produces bilateral mechanical allodynia in hindpaws with evoked (in response to mechanical stimuli) neuronal hyperexcitability in lumbar spinal wide dynamic range (WDR) neurons compared to sham controls. The mechanical allodynia and the evoked activity of WDR neurons is attenuated by intrathecal and topical administration of SB203580, an inhibitor of p-38 MAPK activation, dose dependently (p<0.05); however, the spontaneous activity showed no significant differences compared to sham controls. After T13 spinal hemisection, significantly increased phosphorylated (activated form) p-38alpha MAPK expression was present in both superficial and deep dorsal horn neurons as well as in microglia, but not in astrocytes, in the lumbar spinal cord compared to sham controls (p<0.05). Intrathecal application of PPF significantly attenuated the expression of phosphorylated p-38alpha MAPK in superficial dorsal horn neurons (10 mM) and in microglia (1 and 10 mM) in the lumbar spinal cord compared to the hemisection group (p<0.05). In conclusion, our present data demonstrate that activated neuronal and microglial, but not astrocytic, p-38alpha MAPK contributes to the maintenance of neuronal hyperexcitability in caudal regions following spinal cord injury.

In this study, we evaluated whether propentofylline, a methylxanthine derivative, modulates spinal glial activation and GABAergic inhibitory tone by modulation of glutamic acid decarboxylase (GAD)(65), the GABA synthase enzyme, in the spinal dorsal horn following spinal cord injury (SCI). Sprague-Dawley rats (225-250 g) were given a unilateral spinal transverse injury, from dorsal to ventral, at the T13 spinal segment. Unilateral spinal injured rats developed robust bilateral hindlimb mechanical allodynia and hyperexcitability of spinal wide dynamic range (WDR) neurons in the lumbar enlargement (L4-L5) compared to sham controls, which was attenuated by intrathecal (i.t.) administration of GABA, dose-dependently (0.01, 0.1, 0.5 microg). Western blotting and immunohistochemical data demonstrated that the expression level of GAD(65) protein significantly decreased on both sides of the lumbar dorsal horn (L4/5) after SCI (p<0.05). In addition, astrocytes and microglia showed soma hypertrophy as determined by increased soma area and increased GFAP and CD11b on both sides of the lumbar dorsal horn compared to sham controls, respectively (p<0.05). Intrathecal treatment with propentofylline (PPF 10 mM) significantly attenuated the astrocytic and microglial soma hypertrophy and mechanical allodynia (p<0.05). Additionally, the Western blotting and immunohistochemistry data demonstrated that i.t. treatment of PPF significantly prevented the decrease of GAD(65) expression in both sides of the lumbar dorsal horn following SCI (p<0.05). In conclusion, our present data demonstrate that propentofylline modulates glia activation and GABAergic inhibitory tone by modulation of GAD(65) protein expression following spinal cord injury.

Central neuropathic pain (CNP) is an important problem following spinal cord injury (SCI), because it severely affects the quality of life of SCI patients. As in the patient population, the majority of rats develop significant allodynia (CNP rats) after moderate SCI. However, about 10% of SCI rats do not develop allodynia, or develop significantly less allodynia than CNP rats (non-CNP rats). To identify transcriptional changes underlying CNP development after SCI, we used Affymetrix DNA microarrays and RNAs extracted from the spinal cords of CNP and non-CNP rats. DNA microarry analysis showed significantly increased expression of a number of genes associated with inflammation and astrocytic activation in the spinal cords of rats that developed CNP. For example, mRNA levels of glial fibrilary acidic protein (GFAP) and Aquaporin 4 (AQP4) significantly increased in CNP rats. We also found that GFAP, S100beta and AQP4 protein elevation persisted for at least 9 months throughout contused spinal cords, consistent with the chronic nature of CNP. Thus, we hypothesize that CNP development results, in part, from dysfunctional, chronically "over-activated" astrocytes. Although, it has been shown that activated astrocytes are associated with peripheral neuropathic pain, this has not previously been demonstrated in CNP after SCI.

We examined MRI of two patients with progressive multifocal leukoencephalopathy (PML), including diffusion-weighted imaging (DWI), with calculation of apparent diffusion coefficients (ADC). The pathology findings of one patient were compared with those of MRI. The lesions had different ADC and DWI appearances, depending on the stage of the disease. Newer lesions and the advancing edge of large lesions had normal-to-low ADC and gave high signal on DWI. Older lesions and the centre of large lesions had increased ADC and gave low signal. High signal on DWI and low ADC mark the regions of active infection and cell swelling, distinguishing them from areas of reparative gliosis.

We have studied three members of a family (mother and two siblings) where the mother and father were first cousins and who presented a history of progressive mental deterioration, hyperkinetic extrapyramidal disorders, and epileptic seizures. They underwent the following examinations: cupremia, cupruria, and level of ceruloplasmin, genetic analysis for SCA1, 2, 3, 6, dentato-rubric-pallido-luysian atrophy, and Huntington's disease, electromyography (EMG), electroencephalography (EEG), brain magnetic resonance imaging (MRI), and investigation of acanthocytes with scanning electron microscopy. Genetic analysis was negative in all patients and acanthocytes were positive. EMG showed an axonal neuropathy in one sibling, EEG showed epileptiform activity in the two siblings, and MRI showed cortical atrophy in all subjects. This family shows the great variability of neuroacanthocytosis and a dominant autosomal transmission, as described only once previously in the literature.

We report the case of a 61-year-old man who was referred to our Institution because of severe hypokalemia, rhabdomyolysis and high blood pressure. Severe hypokalemia may lead to rhabdomyolysis. The plasma aldosterone concentrations were low and the plasma renin activity was suppressed. A diagnosis of apparent mineralocorticoid excess, attributable to licorice and grapefruit juice ingestion, was made. Glycyrrhizic acid and glycyrrhetinic acid, its hydrolytic product, in licorice extracts, and polyphenols, in grapefruit juice, can inhibit 11 beta-hydroxysteroid dehydrogenase type 2, the enzyme that converts cortisol to cortisone. Moreover, having suspended licorice and grapefruit juice ingestion, the plasma K+ levels and blood pressure values progressively and simultaneously returned to normal. We would like to stress the diagnostic weight of a careful history taking.

Twelve patients undergoing radiotherapy for pharyngo-laryngeal neoplasms were compared to a control group by means of duplex-Doppler US in order to evaluate early and late radiation-induced damage to the main arterial vessels in the neck region. On first examination the case distribution regarding the presence/absence of preexisting vascular lesions was: no lesions (8.3%), mild (33.3%), moderate (16.6%), and severe (41.6%) atherosclerotic lesions. The subjects included in the control group presented with similar characteristics, so that they had similar features to the patients undergoing radiotherapy. While no early complications were demonstrated, development and/or progression of parietal lesions were detected 1 year after the first examination in 58% of patients. No variations were observed in the control group. Radiation-induced damage to the arterial wall was subdivided into 2 groups: moderate (42%) and severe (16%). Damage to neck vessels, though allowing for the small number of patients and the short follow-up, has to be referred to radiotherapy, since no changes were detected in the control group. In the authors' opinion, follow-up by means of hematochemical exams and duplex-Doppler US of the neck is advisable to evaluate general risk factors and to select those patients who can fruitfully undergo surgical treatment.

Numerous studies have proved the benefit of the use of postoperative radiotherapy in the treatment of malignant cerebral gliomas. The data concerning the efficiency of the treatment of unoperated gliomas are rather scarce. The data obtained in 28 cases of malignant cerebral gliomas, defined as inoperable and treated with radio-chemotherapy, are reported. The diagnosis was obtained through radiological and bioptic examination (21 out of 28). Using a proper treatment with cortisone "dexamethasone" at a dose of 8-16 mg/day, with telecobaltotherapy, we have reached in almost all cases (26 out of 28) doses of 60 Gy, without significant side-effects. All patients were given BCNU as chemotherapy at a dose of 80 mg/m2 every 8 weeks. The resulting average survival rate of 36 weeks, verified through CT, confirms the validity of radio-chemotherapeutical treatment. This type of treatment has been proved useful not only for prolonging the life of these patients, but also improving the quality of their life.

Primary brain lymphomas are usually treated with surgery in combination with radiotherapy, whereas only a few cases have been treated with chemotherapy. We describe a case of a 68-year-old man with an immunoblastic primary cerebral lymphoma first treated with surgery and radiotherapy and subsequently with chemotherapy consisting of cyclophosphamide, adriamycin, vincristine and prednisone (CHOP). In this case immunological study of the peripheral blood and cerebrospinal fluid (CSF) lymphocytes confirmed that a primary brain lymphoma may be an intrinsic cerebral neoplasm with different forms of spreading within the central nervous system (CNS). The period of survival of our patient is equivalent to that of patients treated with radiotherapy alone or in combination with surgery. This suggests the need for further investigation in this field.