JNS-cover.jpgJournal of Neurological Sciences

Vol 352 | No. 1-2 | 15 May 2015 | Pages 1-136


The potential use of mesenchymal stem cells in stroke therapy—From bench to bedside

Adriana Octaviana Dulamea

Stroke is the second main cause of morbidity and mortality worldwide. The rationale for the use of mesenchymal stem cells (MSCs) in stroke is based on the capacity of MSCs to secrete a large variety of bioactive molecules such as growth factors, cytokines and chemokines leading to reduction of inflammation, increased neurogenesis from the germinative niches of central nervous system, increased angiogenesis, effects on astrocytes, oligodendrocytes and axons. This review presents the data derived from experimental studies and the evidence available from clinical trials about the use of MSCs in stroke therapy.

Factors predicting post-stroke aphasia recovery

Watila M.M., Balarabe S.A.

Aphasia is an important stroke sequel that impacts negatively on the HQoL of stroke patients. Although a number of stroke patients with aphasia will have good functional recovery, many are left with language deficits.

Fragile X premutation carriers: A systematic review of neuroimaging findings

Stephanie S.G. Brown, Andrew C. Stanfield

Expansion of the CGG repeat region of the FMR1 gene from less than 45 repeats to between 55 and 200 repeats is known as the fragile X premutation. Carriers of the fragile X premutation may develop a neurodegenerative disease called fragile X-associated tremor/ataxia syndrome (FXTAS). Recent evidence suggests that premutation carriers experience other psychiatric difficulties throughout their lifespan.


Original Articles

Exome sequencing identifies a novel intronic mutation in ENG that causes recurrence of pulmonary arteriovenous malformations

Naoki Saji, Toshitaka Kawarai, Ryosuke Miyamoto, Takahiro Sato, Hiroyuki Morino, Antonio Orlacchio, Ryosuke Oki, Kazumi Kimura, Ryuji Kaji

Hereditary hemorrhagic telangiectasia (HHT) occasionally can be discovered in patients with cerebrovascular disease. Pulmonary arteriovenous malformation (PAVM) is one of the complications in HHT and occasionally is causative for life-threatening embolic stroke. Several genetic defects have been reported in patients with HHT. The broad spectrum of phenotype and intrafamilial phenotype variations, including age-at-onset of vascular events, often make an early diagnosis difficult. We present here a Japanese family with a novel intronic heterozygous mutation of ENG, which was identified using whole exome sequencing (WES).  

Managing excessive saliva with salivary gland irradiation in patients with amyotrophic lateral sclerosis

Alexander Slade, Sinisa Stanic

A significant fraction of patients with amyotrophic lateral sclerosis (ALS) are unable to swallow saliva, which may result in the spillage of saliva outside of the oral cavity. Although anticholinergic agents and botulin toxin injections are considered the first line of treatment, they have not been effective for all patients. We performed a literature search on therapeutic salivary gland irradiation in patients with ALS.

HLA-DRB1 does not have a role in clinical response to interferon-beta among Iranian multiple sclerosis patients

Sara Samadzadeh, Elnaz Tabibian, Tayebeh Sabokbar, Abbas Shakoori, Shahram Rahimi Dehgolan, Saeed Azad Armaki, Bahram Aslanbeigi, Roya Abolfazli

The role of human leukocyte antigen (HLA) in clinical response to immunotherapy is not completely known. In this study we evaluated the relationship between HLA-DRB1 genotype, which has been proved to be more common in Iranian MS patients, and clinical response to interferon-beta (IFNβ), which is the most common immunotherapy for relapsing–remitting MS.

Tic-reducing effects of music in patients with Tourette's syndrome: Self-reported and objective analysis

Sabine Bodeck, Claudia Lappe, Stefan Evers

Self-reports by musicians affected with Tourette's syndrome and other sources of anecdotal evidence suggest that tics stop when subjects are involved in musical activity. For the first time, we studied this effect systematically using a questionnaire design to investigate the subjectively assessed impact of musical activity on tic frequency (study 1) and an experimental design to confirm these results (study 2).

Neuron-restrictive silencer factor in periaqueductal gray contributes to remifentanil-induced postoperative hyperalgesia via repression of the mu-opioid receptor

Cui'e Lu, Linyu Shi, Juan Zhang, Mingjian Kong, Yue Liu, Yu Zhou, Li Xu, Jianhua He, Zhengliang Ma, Xiaoping Gu

The ultra-short-acting mu-opioid receptor (MOR) agonist remifentanil induces postoperative hyperalgesia both in preclinical and clinical research studies. However, the precise mechanisms remain unclear, although changes in opioid receptor expression might be a correlative feature. Neuron-restrictive silencer factor (NRSF) functions as a crucial regulator of MOR expression in specific neuronal cells. Using a mouse model of incisional postoperative pain, we assessed the expression of MOR and NRSF and investigated whether disruption of NRSF expression could prevent the postoperative nociceptive sensitization induced by surgical incision and subcutaneous infusion of remifentanil.

A longitudinal study of the Friedreich Ataxia Impact Scale

Geneieve Tai, Eppie M. Yiu, Louise A. Corben, Martin B. Delatycki

Quality of life in Friedreich ataxia (FRDA) has been explored using various generic health status measurement tools, most commonly the Short Form Health Survey Version 2 (SF-36v2). The tool did not address many specific issues related to disease impact in people with FRDA. The Friedreich Ataxia Impact Scale (FAIS) was developed to examine clinically relevant areas in FRDA. The aims of the current study were to assess the relationship between the FAIS and clinical characteristics of FRDA, as well as to determine the responsiveness of the FAIS to change over one and two years

"Non-classical" paraneoplastic neurological syndromes associated with well-characterized antineuronal antibodies as compared to "classical" syndromes — More frequent than expected

Benjamin Berger, Patricia Bischler, Rick Dersch, Tilman Hottenrott, Sebastian Rauer, Oliver Stich

Paraneoplastic neurological syndromes (PNSs) are rare disorders in association with cancer and sub-divided into "classical" and "non-classical" syndromes according to a 2004 consensus paper proposed by a panel of PNS experts. "Classical" PNSs are regarded to account for the vast majority of cases. However, systematic reports on clinical PNS manifestations are rare. Therefore, we analyzed the spectrum of PNS in our clinic.

Blocking PAR2 attenuates oxaliplatin-induced neuropathic pain via TRPV1 and releases of substance P and CGRP in superficial dorsal horn of spinal cord

Kun Chen, Zhi-Fa Zhang, Ming-Feng Liao, Wen-Long Yao, Juan Wang, Xue-Ren Wang

Oxaliplatin (OXL) is a third-generation chemotherapeutic agent commonly used to treat metastatic digestive tumors; however, neuropathic pain is one of the main limiting complications of OXL. The purpose of this study was to examine the underlying mechanisms by which neuropathic pain is induced by OXL in a rat model. Our results demonstrated that blocking spinal proteinase-activated receptor 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) attenuated pain responses evoked by mechanical stimulation and decreased the releases of substance P and CGRP in the superficial dorsal horn of the spinal cord.

Serum levels of procalcitonin and high sensitivity C-reactive protein are associated with long-term mortality in acute ischemic stroke

You-Mei Li, Xue-Yuan Liu

The aim of this study is to assess the prognostic value of systemic inflammation, as measured by the inflammatory biomarkers PCT and Hs-CRP, to predict the long-term mortality in ischemic stroke patients.

Characterization of spheroids in hereditary diffuse leukoencephalopathy with axonal spheroids

Chenghua Jin, Yukihiko Washimi, Kunihiro Yoshida, Yoshio Hashizume, Ikuru Yazawa

Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a neurodegenerative disease clinically characterized by slowly progressive cognitive decline and motor dysfunction. Neuropathology shows diffuse degeneration in the white matter, with prominent presence of widespread axonal spheroids. To investigate the mechanism underlying HDLS neurodegeneration, we characterized spheroids and examined their development in the degenerated white matter. Analysis revealed that the spheroids are an early neuropathological manifestation in the white matter degeneration and involve axonal component proteins and α-synuclein.

B-cell-activating factor belonging to the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) levels in cerebrospinal fluid of patients with meningoencephalitis

Akio Kimura, Nobuaki Yoshikura, Akihiro Koumura, Yuichi Hayashi, Takashi Inuzuka

The B-cell-activating factor belonging to the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) are important factors for the survival of transitional and mature B cells. High levels of BAFF and APRIL are present in adults with several autoimmune diseases. However, there are few reports about BAFF and APRIL levels in the cerebrospinal fluid (CSF) of patients with meningoencephalitis. We evaluated BAFF and APRIL levels in CSF samples from patients with viral meningitis (VM) (28 patients), autoimmune encephalitis (AE) associated with antineuronal antibodies (15 patients), idiopathic normal pressure hydrocephalus (iNPH) (11 patients), herpes simplex encephalitis (HSE) (9 patients), bacterial meningitis (BM) (6 patients), and cryptococcal meningitis (CM) (4 patients).

Neurofilament light chain level in cerebrospinal fluid can differentiate Parkinson's disease from atypical parkinsonism: Evidence from a meta-analysis

Wataru Sako, Nagahisa Murakami, Yuishin Izumi, Ryuji Kaji

A reliable test that facilitates the accurate diagnosis of Parkinson's and disorders will help with both, clinical management and therapeutic research. In this context, neurofilament light chain (NFL) is candidate for a biomarker in cerebrospinal fluid (CSF). A comprehensive literature search yielded 4 eligible studies. We expressed between-group difference of NFL concentration in CSF as the standardized mean difference. Four studies involved 166 Parkinson's disease (PD), 116 multiple system atrophy (MSA) and 73 progressive supranuclear palsy (PSP) patients.            

Vitamin D receptor gene polymorphisms and Parkinson's disease in a population with high ultraviolet radiation exposure

Nicole M. Gatto, Janet S. Sinsheimer, Myles Cockburn, Loraine A. Escobedo, Yvette Bordelon, Beate Ritz

A high prevalence of vitamin D deficiency has been reported in Parkinson's disease (PD). Epidemiologic studies examining variability in genes involved in vitamin D metabolism have not taken into account level of exposure to ultraviolet radiation (UVR). We examined whether exposure to UVR (as a surrogate for vitamin D levels) and variations in the vitamin D receptor gene (VDR) are associated with PD


Short Communications

Identification of environmental sounds and melodies in syndromes of anterior temporal lobe degeneration

Hannah L. Golden, Laura E. Downey, Philip D. Fletcher, Colin J. Mahoney, Jonathan M. Schott, Catherine J. Mummery, Sebastian J. Crutch, Jason D. Warren

Recognition of nonverbal sounds in semantic dementia and other syndromes of anterior temporal lobe degeneration may determine clinical symptoms and help to define phenotypic profiles. However, nonverbal auditory semantic function has not been widely studied in these syndromes. Here we investigated semantic processing in two key nonverbal auditory domains – environmental sounds and melodies – in patients with semantic dementia (SD group; n = 9) and in patients with anterior temporal lobe atrophy presenting with behavioural decline (TL group; n = 7, including four cases with MAPT mutations) in relation to healthy older controls (n = 20).

Two families with novel missense mutations in COL4A1: When diagnosis can be missed

Elisa Giorgio, Giovanna Vaula, Giovanni Bosco, Sara Giacone, Cecilia Mancini, Alessandro Calcia, Simona Cavalieri, Eleonora Di Gregorio, Roberta Rigault De Longrais, Sabrina Leombruni, Lorenzo Pinessi, Paolo Cerrato, Alfredo Brusco, Alessandro Brussino

Mutations in COL4A1, encoding one of the six collagen type IV proteins, cover a wide spectrum of autosomal dominant overlapping phenotypes including porencephaly, small-vessel disease and hemorrhagic stroke, leukoencephalopathy, hereditary angiopathy with nephropathy, aneurysms and muscle cramp (HANAC) syndrome, and Walker–Warburg syndrome. Over 50 mutations are known, mainly being missense changes. Intra- and inter-familial variability has been reported. We studied two Italian families in which the proband had a clinical diagnosis of COL4A1-related disorder.


Letters to the Editor

Case report: A Chinese child with Andersen–Tawil syndrome due to a de novo KCNJ2 mutation

Xiao-li Liu, Xiao-jun Huang, Xing-hua Luan, Hai-yan Zhou, Tian Wang, Jing-yi Wang, Jun-yi Shen, Sheng-di Chen, Hui-dong Tang, Li Cao
  • DOI: http://dx.doi.org/10.1016/j.jns.2015.02.027
  • p105–106
  • Published online: February 20, 2015
  • Abstract
  • Full-Text HTML
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The patient is a 15-year-old male, who has a history of paroxysmal weakness in the limbs. Since two years old, he has suffered from flaccid tetraplegia attack with conscious mind, accompanied by lower limb soreness. He experienced two or three attacks with the analogous phenotype per year since then, from which he recovered gradually within two or three days after potassium supplement. These attacks were triggered by many factors, such as cold, influenza, diarrhea, vigorous exercise and so on, seeming more frequently in the spring.        

Appendicular ataxia without position sense loss in a patient with parietal lobe infarct

Ashkan Mowla, Haris Kamal, S. Ali Nabavizadeh

A 86-year-old lady presented with sudden onset of appendicular ataxia of the right arm with minimal weakness and no deep sensory loss. On neurological exam, she had minimal pronator drift. She had undershooting and overshooting on attempting to reach the target finger on finger to nose test. She also has dysdiadokokinesia and uncontrolled rebound. The tests were not worsened with eyes closed. The sensory exam was unremarkable including normal proprioception. Her brain MRI showed an area of acute infarct in left posterior parietal lobe (Fig. 1) and no other lesion.

Creutzfeldt–Jakob disease with homozygous M232R mutation: A case report

Tomoya Kon, Yasuo Miki, Akira Arai, Yukihisa Funamizu, Tatsuya Ueno, Rie Haga, Haruo Nishijima, Chieko Suzuki, Jin-ichi Nunomura, Masayuki Baba, Yoshinobu Oyama, Yusei Shiga, Tetsuyuki Kitamoto, Masahiko Tomiyama

Creutzfeldt–Jakob disease (CJD) is a fatal neurodegenerative disease characterized by accumulation of an abnormal isoform of prion protein. More than 30 polymorphisms and mutations of the prion protein gene (PRNP) are involved in the development of genetic CJD [1]. A substitution from methionine to arginine at the PRNP codon 232 (M232R) is the fourth most frequent mutation in Japanese genetic prion disease (approximately 15%) [2]. However, the pathogenic roles of M232R substitution for CJD have been controversial [3], and all reported CJD patients with M232R mutation carry the heterozygous substitution [2].

Eye of the tiger sign in a 23 year patient with mitochondrial membrane protein associated neurodegeneration

Marta Skowronska, Tomasz Kmiec, Iwona Kurkowska-Jastrzębska, Anna Czlonkowska

Neurodegeneration with brain iron accumulation (NBIA) involves several genetic disorders with markedly excessive regional brain iron stores. In addition to pantothenate kinase-associated neurodegeneration (PKAN), caused by a mutation in the PANK2 gene, which accounts for at least one-half of (NBIA) cases, several other genetic causes have been identified [1]. NBIA subtype, mitochondrial membrane protein associated neurodegeneration (MPAN) is caused by mutation in the orphan gene C19orf12, which encodes a protein expressed in mitochondria, but its role has not been fully understood [2].

Delayed diagnosis of vestibular epilepsy due to temporal cavernous malformation

Sun-Uk Lee, Chang-Ho Yun, Ji-Soo Kim

Vestibular epilepsy refers to recurrent seizures that cause dizziness/vertigo as a sole or predominant symptom [1]. It is due to epileptic discharges from the vestibular cortices mostly residing in the temporal [2] or temporo-parietal areas [3–5] but also in the frontal cortex [6]. Cerebral cavernous malformations, an enlarged collection of vascular channels invading adjacent brain tissue, mostly present with recurrent seizures in the supratentorial areas. Vestibular epilepsy has been reported in oligodendroglioma [7] and astrocytoma [6], but has not been described in association with a cavernous malformation.

Very prolonged capsular warning syndrome

Naoki Makita, Yasumasa Yamamoto, Yoshinari Nagakane, Shinji Ashida, Toshiki Mizuno

Capsular warning syndrome (CWS) was first described by Donnan in 1993 to describe recurrent stereotyped episodes of transient ischemic attacks (TIAs) that often lead to infarction in the corresponding anatomical location, usually in the lenticulostriate artery territory [1]. The mechanism is believed to be small single perforating artery disease. A hemodynamic ischemic process in the territory of the penetrating arteries caused by high-grade stenosis of proximal penetrating arteries due to microatherosclerosis has been postulated [1–3].

Heparin-responsive angiopathy in the central nervous system caused by intravascular large B-cell lymphoma

Shun Yoshida, Hiroshi Kuroda, Noriko Fukuhara, Hidehiko Konno, Mika Watanabe, Tetsuya Akaishi, Maki Tateyama, Masashi Aoki

Intravascular large B-cell lymphoma (IVLBCL) is characterized by an intraluminal proliferation of lymphoma cells, which frequently causes vascular occlusive disorders in the central nervous system (CNS) [1]. Although the advent of rituximab has improved the survival of patients with B-cell lymphoma [2], the treatment for neurological deficits caused by IVLBCL-associated angiopathy has not yet been established. Here, we report a patient with CNS-IVLBCL, responding to subacute heparin administration.

Tuberculous optic neuritis: A case report

Anu Gupta, Manoj Kumar Goyal, Manish Modi, Vivek Lal

A 37 years old diabetic male presented with a history of painless progressive visual loss in his right eye for 5 days followed by visual loss in the left eye for 2 day duration. He also had moderate grade fever on and off for the past 7 days. He denied any history of headache, loss of weight or appetite or any other systemic symptoms. On presentation he was not able to perceive light in the right eye and had a visual acuity of 20/200 in the left eye. This progressed over 3 days to no perception of light in the left eye.             

Fatal intracerebral haemorrhage following intravenous thrombolysis for acute ischaemic stroke: A hidden role for cerebral amyloid angiopathy?

Onte Ntlholang, Michael Farrell, Imelda Noone, Andreas Charidimou, Morgan Crowe

Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is currently the only approved therapy for acute ischemic stroke. However, intracerebral haemorrhage (ICH) remains the most feared and devastating complication of intravenous thrombolysis [1]. We report a case of a patient who suffered a catastrophic haemorrhage following intravenous thrombolysis for stroke, related to previously unsuspected severe cerebral amyloid angiopathy (CAA) found on autopsy.

Acute ischemic strokes from small vessel vasculitis due to disseminated histoplasmosis infection

Robert D. Bolen, Cheryl D. Bushnell, Patrick S. Reynolds

A 61 year old previously healthy male with recent diagnosis of disseminated histoplasmosis presented due to transient right hand numbness and word finding difficulties. Neurologic exam was normal on our evaluation. The patient had presented 6 weeks prior with night sweats, weight loss, and fever and was eventually diagnosed with disseminated histoplasmosis. Work-up that led to the diagnosis included CT chest showing pulmonary nodules and lymphadenopathy, as well as blood cultures and bone marrow biopsy both positive for Histoplasma capsulatum.

Long-term follow-up of immunotherapy-unresponsive recurrent tumefactive demyelination

Delon La Puma, Sara Llufriu, Maria Sepúlveda, Yolanda Blanco, Teresa Ribalta, Francesc Graus, Albert Saiz

Recurrences of tumefactive demyelinating lesions (TDL) are very infrequent, and most of them occur in the context of multiple sclerosis (MS) [1]. Hence, the initial diagnosis, and prediction of the subsequent course and therapeutic strategy of isolated TDL are challenging. We report a patient with biopsy-proven idiopathic TDL who presented with seven tumefactive relapses over eleven years of follow-up despite the use of several types of immunotherapy.

Metronidazole-induced encephalopathy with contrast enhancing lesions on MRI

Shogo Furukawa, Tatsuya Yamamoto, Atsuhiko Sugiyama, Kenji Ohira, Yuya Aotsuka, Kyosuke Koide, Kazuho Kojima, Satoshi Kuwabara

Subacute progressive encephalopathy is a rare complication of metronidazole treatment [1,2]. Previous reports have shown characteristic findings on brain magnetic resonance imaging (MRI), but detailed serial findings have rarely been described. We herein report a patient with metronidazole-induced encephalopathy who initially showed gadolinium-enhanced lesions in the corpus callosum, typical for the disorder. However, follow-up MRI revealed prominent cystic changes in the bilateral white matter and corpus callosum.

Diffuse leptomeningeal carcinomatosis mimicking brain death

Nathan H. Kung, Rajat Dhar, Salah G. Keyrouz

A state of complete de-afferentation and/or de-efferentation of the brain mimicking brain death has been reported in rare cases of fulminant Guillain–Barre syndrome (GBS) [1–4]. Distinguishing such conditions from actual brain death is imperative, as not only are such patients still alive, but they may recover. A similar degree of catastrophic polyradiculopathy from disorders other than GBS has not been reported, but would be similarly important to recognize and differentiate. To our knowledge, we report the first case of complete cerebral disconnection due to diffuse leptomeningeal carcinomatosis.

Bilateral medial medullary infarction presenting as Guillain Barré Syndrome: A diagnostic challenge

Mayra Montalvo, Rushna Ali, Muhib Khan

Medial medullary infarction (MMI) is an uncommon entity (0.5–1.5% of all strokes), and bilateral MMI is extremely rare [1,2]. Although quadriparesis, loss of deep sensation and hypoglossal palsy have been described as the classical picture for bilateral MMI, the clinical presentation is variable and non-specific, usually delaying diagnosis [2]. Moreover, initial diffusion weighted imaging (DWI) is often negative [3]. Bilateral MMI can be misdiagnosed as Guillain Barré Syndrome (GBS), since patients present with sudden onset of quadriparesis, sensory disturbances, bulbar dysfunction and progression to respiratory failure [2,4].