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Toxic leukoencephalopathy is a rare but critical neurological disorder in heroin abusers. Our aim is to compare the clinical manifestations, brain MRIs and prognoses of heroin-induced leukoencephalopathy by different intake routes. We present two patients with toxic leukoencephalopathy caused by intravenous (IV) injection of heroin and 48 additional cases from systematic reviews of the literature published between 1994 and 2018. Among the 50 heroin abusers who developed leukoencephalopathy, inhalation was the most popular route (60%), followed by IV injection (30%) and snorting (10%). Mental changes, mutism and urine/fecal incontinence were the major symptoms in patients who IV injected heroin, while cerebellar ataxia and dysarthria were more common among those who inhaled heroin. Delayed-onset encephalopathy uniquely occurred in those who IV injected heroin, whereas progressive encephalopathy was more commonly observed in those who inhaled heroin. Clinical improvement was observed in 60% of patients, the overall mortality rate was 12%, and higher mortality was observed in patients who used the inhalation route (16.7%). The hallmarks on the MRIs of those who inhaled heroin were posterior to anterior involvement of the cerebral white matter and lesions in the posterior limbs of the internal capsules, cerebellum and brainstem. In contrast, those who IV injected heroin had more frequent lesions in the subcortical U fibers and the genu of the internal capsules. These data could help physicians make an early diagnosis and predict prognosis and suggest that prompt antioxidative or symptomatic treatments might reduce the long-term consequences and mortality of heroin-induced leukoencephalopathy.

In this study, we present the clinical manifestations, brain magnetic resonance imaging (MRI) and concurrent polyneuropathies in two patients with non-alcoholic Wernicke's encephalopathy (WE) after gastrojejunostomy (Billroth II) anastomosis procedures. These patients developed sub-acute onset of disorientation and disturbance of consciousness following several weeks of poor intake. Peripheral neuropathy of varying severity was noted before and after the onset of WE. Brain MRI of the patients showed cerebellar vermis and symmetric cortical abnormalities in addition to typical WE changes. Electrophysiological studies demonstrated axonal sensorimotor polyneuropathy. Prompt thiamine supplement therapy was initiated and both patients gradually recovered, however mild amnesia was still noted 6 months later. We reviewed non- alcoholic WE with atypical cortical abnormalities in English language literatures and identified 29 more cases. Eight out of 31 (25.8%) patients died during follow-up. Nine patients with gait disturbance or motor paresis had showed hyporeflexia in neurological examinations. In addition to classic triad, seizure was recorded in seven patients. Dietary deprivation is a risk factor for non-alcoholic WE among elderly patients receiving gastrointestinal surgery. The prognosis is good after thiamine supplement therapy. Recognizing the MRI features and predisposing factors in patients who have undergone gastrectomy can aid in the diagnosis and management.

Several studies have shown that the mu opioid receptor (MOR) located in the peripheral nerves can be activated after nerve injury and that it attenuates peripheral nociceptive signals to the spinal dorsal horn. Various cytokines and phosphorylated-p38 (p-p38) activation in the dorsal horn also play an important role in neuropathic pain development. Granulocyte-colony stimulating factor (GCSF) is a growth factor that can stimulate granulocyte formation and has been shown to exert an analgesic effect on neuropathic pain through recruiting opioid-containing leukocytes to the injured nerve. However, the underlying mechanisms are not well understood. Herein, the results of behavior tests in addition to MOR levels in the injured sciatic nerve and the levels of p-p38 and various cytokines in the spinal dorsal horn were studied in vehicle-treated or GCSF-treated chronic constriction injured (CCI) rats at different time points (i.e., 1, 3 and 7 days, respectively) after nerve injury. The results showed that a single early systemic GCSF treatment after nerve injury can up-regulate MORs in the injured nerve, which can decrease peripheral nociceptive signals. Thereafter, those changes suppress the pro-inflammatory cytokine IL-6 but enhance the anti-inflammatory cytokine IL-4, followed by decreases in p-p38 in the dorsal horn and thus further attenuate neuropathic pain.

The purpose of this article is to investigate the relationship between clinical features and imaging characteristics of spinal cord infarction (SCI). Twenty patients (11 women/9 men) were diagnosed at the Chang Gung Memorial Hospital between March 1993 and March 2007. Data of clinical features, possible causes and imaging findings were collected and analyzed retrospectively. Their average age was 56.6 +/- 15.5 years. Possible causes of SCI were found in 16 patients (80%), including 8 (40%) who had a high risk of atherosclerosis, 5 (25%) who had aortic diseases, and 3 (15%) who had adjacent spinal diseases; the other 4 (20%) were cryptogenic. Seven patients had concomitant SCI and vertebral body infarctions, and four of them had aortic diseases. Most of the vertebral body infarctions were seen in the thoracolumbar regions (p = 0.008, chi(2) test) and were adjacent to their cord lesions. Twelve patients (60%) had poor outcomes (mortality, unable to walk, or able to walk with two aids). Younger patients (or=55 year-old) with long cord lesions (greater than or equal to three vertebral segments) had poorer outcomes than older patients with short cord lesions. Vertebral abnormalities are not uncommon, but easily overlooked in SCI. Furthermore, concomitant SCI and vertebral body infarctions were usually located at the thoracolumbar regions, and highly associated with patients with aortic diseases (p = 0.03, chi(2) test). An understanding of the spinal cord and vertebral vascular supply greatly benefits in early diagnosis, etiological illumination, and prognostic prediction of SCI.

Recent results show that brain glucocorticoids are involved in the dysregulation of fear memory extinction in post-traumatic stress disorder patients. The present study was aimed to elucidate the possible mechanism of glucocorticoids on the conditioned fear extinction. To achieve these goals, male SD rats, fear-potentiated startle paradigm, and Western blot were used. We found that (1) systemic administration of the synthetic glucocorticoid agonist dexamethasone (DEX) facilitated extinction of conditioned fear in a dose-dependent manner (0.05, 0.1, 0.5, or 1.0 mg/kg, i.p.); (2) systemic administration of the glutamate NMDA receptor antagonist (+/-)-HA966 (6.0 mg/kg, i.p.) and intra-amygdala infusion of the NMDA receptor antagonists MK801 (0.5 ng/side, bilaterally) or D,L-2-amino-5-phosphonovaleric acid (AP5, 2.0 ng/side, bilaterally) blocked the DEX facilitation effect; (3) the corticosteroid synthesis inhibitor metyrapone (25 mg/kg. s.c.) blocked extinction and this was prevented by co-administration of NMDA receptor agonist D-cycloserine (DCS, 5.0 mg/kg, i.p.); (4) co-administration of DEX and DCS in subthreshold doses provided a synergistic facilitation effect on extinction (0.2 and 5 mg/kg, respectively). Control experiments indicated that co-administration of DEX and DCS did not alter the expression of conditioned fear and the effect was not due to lasting damage to the amygdala. These results suggest that glutamate NMDA receptors within the amygdala participate in the modulatory effect of glucocorticoids on extinction.

Trinucleotide repeat (TNR) expansion in the gene for TATA binding protein (TBP) has recently been described as causal for spinocerebellar ataxia type 17. The normal number of repeats has been considered to be 42 or less. An intermediate range with reduced penetrance has been assumed to be 43-47 CAA/CAG repeats. We examined this gene in 30 patients with autosomal-dominant cerebellar ataxia (ADCA), 35 patients with sporadic ataxia, 11 patients with Huntington's disease (HD), 351 patients with idiopathic Parkinson's disease (PD), 105 patients with Alzheimer's disease (AD), and 291 controls with no history of neurodegenerative disease. Three patients (one with sporadic PD and two with AD) carrying more than 42 TNRs in the TBP gene were identified. This reveals that the phenotype associated with CAG/CAA expansion in the TBP gene may be heterogeneous.

In the original publication of the article, author name Hong-Shiu Chang was incorrectly written as Hong-Chiu Chang.

Background Painful ophthalmoplegia with normal cranial imaging is rare and confined to limited etiologies. In this study, we aimed to elucidate these causes by evaluating clinical presentations and treatment responses. Methods Cases of painful ophthalmoplegia with normal cranial MRI at a single center between January 2001 and June 2011 were retrospectively reviewed. Diagnoses of painful ophthalmoplegia were made according to the recommendations of the International Headache Society. Results Of the 58 painful ophthalmoplegia cases (53 patients), 26 (44.8%) were diagnosed as ocular diabetic neuropathy, 27 (46.6%) as benign Tolosa-Hunt syndrome (THS), and 5 (8.6%) as ophthalmoplegic migraine (OM). Patients with ocular diabetic neuropathy were significantly older (62.8 ± 7.8 years) than those with benign THS (56.3 ±12.0 years) or OM (45.8 ± 23.0 years) (p p p Conclusions Ocular diabetic neuropathy and benign THS accounted for most of the painful ophthalmoplegias in patients with normal cranial imaging. Patient outcomes were generally good.

Background During inflammation, immune cells accumulate in damaged areas and release pro-inflammatory cytokines and neurotrophins. Brain-derived neurotrophic factor (BDNF) plays a neuromodulatory role in spinal cord dorsal horn via the post-synaptic tyrosine protein kinase B (trkB) receptor to facilitate pain transmission. However, the precise role of BDNF and trkB receptor in the primary sensory neurons of dorsal root ganglia (DRG) during inflammation remains to be clarified. The aim of this study was to investigate whether and how BDNF-trkB signaling in the DRG is involved in the process of inflammatory pain. Methods We used complete Freund's adjuvant- (CFA-) induced and tumor necrosis factor-α- (TNF-α-) induced inflammation in rat hindpaw as animal models of inflammatory pain. Quantification of protein and/or mRNA levels of pain mediators was performed in separate lumbar L3-L5 DRGs. The cellular mechanism of TNF-α-induced BDNF and/or trkB receptor expression was examined in primary DRG cultures collected from pooled L1-L6 DRGs. Calcitonin gene-related peptide (CGRP), BDNF and substance P release were also evaluated by enzyme immunoassay. Results CFA injection into rat hindpaw resulted in mechanical hyperalgesia and significant increases in levels of TNF-α in the inflamed tissues, along with enhancement of BDNF and trkB receptor as well as the pain mediators CGRP and transient receptor potential vanilloid receptor subtype 1 (TRPV1) in DRG. Direct injection of TNF-α into rat hindpaw resulted in similar effects with retrograde transport of TNF-α along the saphenous nerve to DRG during CFA-induced inflammation. Primary DRG cultures chronically treated with TNF-α showed significant enhancement of mRNA and protein levels of BDNF and trkB receptor, BDNF release and trkB-induced phospho-ERK1/2 signal. Moreover, CGRP and substance P release were enhanced in DRG cultures after chronic TNF-α treatment or acute BDNF stimulation. In addition, we found that BDNF up-regulated trkB expression in DRG cultures. Conclusions Based on our current experimental results, we conclude that inflammation and TNF-α up-regulate the BDNF-trkB system in DRG. This phenomenon suggests that up-regulation of BDNF in DRG may, in addition to its post-synaptic effect in spinal dorsal horn, act as an autocrine and/or paracrine signal to activate the pre-synaptic trkB receptor and regulate synaptic excitability in pain transmission, thereby contributing to the development of hyperalgesia.