Journal of the Neurological Sciences

Editorial Board

2010-09-15

Why mesial temporal lobe epilepsy with hippocampal sclerosis is progressive: Uncontrolled inflammation drives disease progression?

Tianhua Yang, Dong Zhou, Hermann Stefan — 2010-07-21

Abstract: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a group of chronic disorders characterized by prominent neuronal loss and gliosis in the hippocampus and amygdala. Newly published data indicate that it may be a progressive disease, but the mechanism underlying the progressive nature remains unknown. Recently, substantial evidence for an inflammatory mechanism in MTLE has been documented. We are therefore presenting a review of literature concerning the effects of uncontrolled inflammation on the disease progression of MTLE-HS. We found that increasing amounts of evidence support the association between uncontrolled inflammation and progression of the disease. Uncontrolled inflammatory processes may be a main mechanism underlying the self-propagating cycle of uncontrolled inflammation, blood-brain barrier damage, and seizures that drive the progressive nature. Thus it is important to unravel the principles of communication between the different factors in this cycle. The dynamic modulation of inflammatory processes aimed at preventing or interrupting this cycle has the potential to emerge as a novel therapeutic strategy. This line of therapy might offer new perspectives on the pharmacologic treatment of seizures, and possibly on delaying disease progression or retarding epileptogenesis as well.

Changes in the volumes of the brain and cerebrospinal fluid spaces after shunt surgery in idiopathic normal-pressure hydrocephalus

2010-07-22

Abstract: Objectives: To investigate volumetric changes of the brain and cerebrospinal fluid (CSF) spaces after shunt surgery in shunt-responsive idiopathic normal-pressure hydrocephalus (iNPH), and correlations between the changes and postoperative clinical improvements.Methods: Twenty-one patients with shunt-responsive iNPH were studied. Magnetic resonance imaging (MRI) of the brain was performed before and 1year after surgery, and clinical symptoms were assessed by the iNPH Grading Scale, a validated assessment tool of the triad of iNPH, the Modified Rankin Scale, the Timed Up and Go Test, and neuropsychological tests including the Mini-Mental State Examination. The volumes of the left cerebral hemisphere, infratentorial brain, ventricles, and suprasylvian and infrasylvian subarachnoid CSF spaces were measured using an MRI-based volumetric technique.Results: The volumes of the cerebral hemisphere and infratentorial brain did not change significantly after shunt surgery (p=0.231, 0.109, respectively). The volumes of the ventricles and infrasylvian subarachnoid CSF spaces were significantly decreased (p<0.0001, <0.05, respectively), with a mean change rate of −26.1% and −4.5%, respectively. The volumes of the suprasylvian subarachnoid CSF spaces increased significantly (p<0.0001), with a mean change rate of 43.5%. The decrease in ventricular volumes was significantly correlated with clinical improvement.

Difference of fibroblast growth factor receptor 1 expression among CA1-3 regions of the gerbil hippocampus after transient cerebral ischemia

2010-07-12

Abstract: Fibroblast growth factors are important regulators of neuronal development. In this study, we observed fibroblast growth factor receptor 1 (FGFR1) immunoreactivity and its protein levels in the hippocampus proper (CA1-3 regions) of the gerbil at various time points after ischemia/reperfusion. In the sham-operated group, FGFR1 immunoreaction was not detected in the hippocampus proper. FGFR1 immunoreaction was first detected in non-pyramidal neurons in the CA1-3 region at 12h and 1day after ischemia/reperfusion. From 2days after ischemia/reperfusion, FGFR1 immunoreaction was found in astrocytes, not in microglial cells, in the CA1 region: FGFR1 immunoreactivity and the number of astrocytes were significantly increased at 5days post-ischemia. Western blot analysis revealed that FGFR1 protein levels were also increased from 1day after ischemia/reperfusion. These results indicate that increase of FGFR1 in astrocytes of the ischemic CA1 region may be associated with gliosis followed by delayed neuronal death.

A novel mutation in FHL1 in a family with X-linked scapuloperoneal myopathy: Phenotypic spectrum and structural study of FHL1 mutations

2010-07-16

Abstract: An X-linked myopathy was recently associated with mutations in the four-and-a-half-LIM domains 1 (FHL1) gene. We identified a family with late onset, slowly progressive weakness of scapuloperoneal muscles in three brothers and their mother. A novel missense mutation in the LIM2 domain of FHL1 (W122C) co-segregated with disease in the family. The phenotype was less severe than that in other reported families. Muscle biopsy revealed myopathic changes with FHL1 inclusions that were ubiquitin- and desmin-positive. This mutation provides additional evidence for X-linked myopathy caused by a narrow spectrum of mutations in FHL1, mostly in the LIM2 domain. Molecular dynamics (MD) simulations of the newly identified mutation and five previously published missense mutations in the LIM2 domain revealed no major distortions of the protein structure or disruption of zinc binding. There were, however, increases in the nonpolar, solvent-accessible surface area in one or both of two clusters of residues, suggesting that the mutant proteins have a variably increased propensity to aggregate. Review of the literature shows a wide range of phenotypes associated with mutations in FHL1. However, recognizing the typical scapuloperoneal phenotype and X-linked inheritance pattern will help clinicians arrive at the correct diagnosis.

Etiology of Konzo, epidemic spastic paraparesis associated with cyanogenic glycosides in cassava: Role of thiamine deficiency?

Bola Adamolekun — 2010-07-12

Abstract: Konzo is a syndrome of symmetrical, non-progressive, non-remitting spastic paraparesis occurring in epidemic and endemic forms in several countries in Africa, invariably associated with monotonous consumption of inadequately processed bitter cassava roots (Manihot esculenta) with very minimal protein supplementation.Despite numerous epidemiological, clinical and biochemical studies by authors in several countries aimed at elucidating the etiological mechanisms of Konzo, the etiology remains unknown. High cyanide consumption with low dietary sulfur intake due to almost exclusive consumption of insufficiently processed bitter cassava roots was proposed as the cause of Konzo, but there has been no evidence of a causal association between cyanide consumption and Konzo.In this paper a new etiological mechanism of thiamine deficiency is presented, based on detailed review of the epidemiological, clinical and biochemical features of Konzo. It is postulated that in Konzo patients, a severe exacerbation of thiamine deficiency results from the inactivation of thiamine that occurs when, in the absence of dietary sulfur-containing amino acids; the sulfur in thiamine is utilized for the detoxification of cyanide consumed in improperly processed bitter cassava. Thiamine is known to be rendered inactive when the sulfur in its thiazole moiety is combined with hydrogen cyanide.This hypothesis may stimulate studies examining the role of thiamine in the etiology of Konzo, and may lead to the formulation of strategies for the prevention and treatment of this debilitating disease.

Association of the −344C/T aldosterone synthase (CYP11B2) gene variant with hypertension and stroke

2010-07-05

Abstract: Stroke is a complex disease caused by combination of multiple risk factors. Recent findings have suggested that stroke has a significant genetic component. Various types of genetic polymorphisms have been suggested to contribute to the risk of stroke. Gene polymorphisms of renin-angiontensin aldosterone system (RAAS) have been suggested to be risk factors for hypertension, cardiovascular diseases and stroke. In the present case–control study we investigated the association of −344C/T (rs179998) polymorphism in the promoter region of the human aldosterone (CYP11B2) gene with genetic predisposition to hypertension, ischemic stroke and stroke subtypes classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Four hundred and three stroke patients (hypertensives:normotensives=219:184) and three hundred and ninety four, sex and age matched healthy controls (hypertensives:normotensives=118:276) were involved in the study. The region of interest in the CYP11B2 gene was amplified by polymerase chain reaction and genotypes determined by subjecting the PCR products to restriction digestion by the enzyme HaeIII. Significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. TT genotype and T allele associated significantly with hypertension and stroke (p<0.000 in hypertension and p=0.000 in case of stroke). A stepwise logistic regression analysis confirmed these findings. To establish that this polymorphism is associated with stroke independent of hypertension, we compared stroke patients without hypertension with normotensive controls. Significant difference was observed in genotypic distribution and allelic frequency between the two groups (p=0.000). Further evaluating the association of this polymorphism with stroke subtypes we found significant associations with intracranial large artery atherosclerosis, lacunar stroke and cardioembolic stroke (p=0.000 in each case). In conclusion our study suggests that −344T allele of CYP11B2 gene is an important risk factor for hypertension and ischemic stroke. However, this is a preliminary study and the results need to be confirmed in a larger cohort.

VEGF/VEGFR-2 changes in frontal cortex, choroid plexus, and CSF after chronic obstructive hydrocephalus

2010-07-12

Abstract: Chronic hydrocephalus (CH) is often associated with decreased cerebral blood flow (CBF) and oxygen levels. While the exact pathophysiology is not clear, vascular endothelial growth factor (VEGF) and its receptor-2 (VEGFR-2) may be involved. Because the choroid plexus (CP) is involved in cerebrospinal fluid (CSF) production and secretes numerous growth factors including VEGF, it is important to understand VEGF/VEGFR-2 levels in the CP–CSF circulatory system. Our results showed significant decreases in CBF and VEGFR-2 levels in frontal cortex (FC) in CH compared with SC; there were no significant changes in VEGF levels. CBF change in FC was positively correlated with VEGFR-2 levels (P=0.024). Immunohistochemistry (IHC) showed robust expression of VEGF/VEGFR-2 in CP. After CH induction, ventricular CSF volume and VEGF levels significantly increased. These results suggest that the decreased VEGFR-2 levels in FC may be contributed to decreased CBF and increased ventricular CSF-VEGF levels possibly reflected a hypoxic response and/or accumulation of VEGF from CP secretion after blockage of CSF outlet. Further investigation into CSF-VEGF levels in different sites may provide a better understanding of VEGF/VEGFR-2 modulation in the normal and hydrocephalic brain, and may represent a feasible approach to potential therapeutic options for hydrocephalus.

Coexistence of parkinsonism, dementia and upper motor neuron syndrome in four Czech patients

Kateřina Farníková, Petr Kaňovský, Igor Nestrašil, Pavel Otruba — 2010-07-12

Abstract: Background: The parkinsonian complex of Guam is an endemic neurodegenerative condition, which has been described only in the islands of the Guam archipelago and at the Kii peninsula of Japan. Up to now, only one “sporadic” case has been described (including the autopsy) in Japan.Study objective: To describe the clinical, laboratory and neurophysiological characteristics of the neurodegenerative disorder presenting in 4 patients with the complex syndrome of parkinsonism, amyotrophic lateral sclerosis (ALS), and dementia.Patients and methods: Four consecutive patients of Caucasian and Czech origin, presenting with the complex syndrome of slowly progressive parkinsonism, amyotrophic lateral sclerosis and dementia were examined clinically, including neuropsychological examination, and they were assessed using magnetic resonance imaging, electromyography and evoked potentials. The blood and CSF samples were also examined, and the levels of inflammatory and neurodegenerative markers (beta-amyloid, cystatin C and tau-proteins) were assessed.Results: The clinical phenotype in all four patients corresponded to the one described in the parkinsonian complex of Guam, including the presence of a cognitive deficit at the level of mild to severe dementia. The findings of EMG examination in all cases were those typically seen in ALS, and they met the El Escorial criteria. CSF levels of neurodegenerative markers (tau-protein) were elevated in all four patients. CSF levels of inflammatory markers were normal.Conclusion: The unique appearance of the syndrome typical for the endemic Guam complex in patients of Caucasian origin in Europe raises a question of endemicity and heredity of the Guam complex and deserves further research.

Intracranial arterial dissections in ischemic stroke assessed by 3D rotational angiography

2010-07-12

Abstract: Background: Dissections involving intracranial arteries are sometimes difficult to assess using conventional digital subtraction angiography (DSA). We evaluated the value of three-dimensional rotational angiography (3D-RA) for the assessment of intracranial arterial dissections (ICADs).Methods: The subjects were 39 patients (26 males, 13 females; average age 50±15years) who were diagnosed as having ICADs and who underwent both DSA and 3D-RA in our hospital between April 1999 and March 2005. We retrospectively compared 3D-RA images to conventional DSA images in a blinded manner with respect to double lumen sign, pearl and string sign, string sign, and aneurysmal dilatation. On the basis of the caliber size of the artery affected by dissections, we divided patients into two groups: smaller artery group (S group) and larger artery group (L group).Results: The detection rate of double lumen sign with 3D-RA (79%) was significantly higher than with conventional DSA (18%; P<0.001). Reliable findings of arterial dissections (double lumen sign and/or pearl and string sign) were observed more often with 3D-RA (90%) than with conventional DSA (36%; P<0.001). In S group, the double lumen sign was detected only with 3D-RA.Conclusions: 3D-RA allows increased conspicuity of ICADs findings with conventional DSA, especially in smaller-caliber intracranial arteries.

A Japanese ALS6 family with mutation R521C in the FUS/TLS gene: A clinical, pathological and genetic report

2010-07-12

Abstract: Here we report a Japanese family with amyotrophic lateral sclerosis (ALS) characterized by very rapid progression, high penetrance and an autosomal dominant mode of inheritance. The phenotype includes atrophy of sternocleidomastoideus muscles, bulbar involvement, weakness of neck muscles and proximal muscle atrophy. These clinical symptoms are reminiscent of myopathy. All patients examined had similar clinical symptoms, age at onset and disease duration. The proband was found to have mutation R521C in the FUS/TLS gene, and was diagnosed as having ALS6. Autopsy material was available from the mother of the proband and FUS-immunoreactive neuronal and glial cytoplasmic inclusions were observed in the anterior horn of the spinal cord. While atrophy and weakness of the sternocleidomastoideus muscle is not emphasized in previous reports, this symptom may be a clinical hallmark of ALS6.

Increased insulin receptor expression in anterior temporal neocortex of patients with intractable epilepsy

Liang Wang, Guangwei Liu, Mei He, Lan Shen, Dinglie Shen, Yang Lu, Xuefeng Wang — 2010-07-12

Abstract: The insulin receptor (IR) is a tyrosine kinase receptor that binds to insulin and plays pivotal roles in energy homeostasis, neuronal growth, neuronal survival, synaptic plasticity and cognitive function. The biological mechanisms of intractable epilepsy involve energy metabolism, neuron loss, neurogenesis and abnormal neural networks. Here, we evaluated the expression of the IR in the anterior temporal neocortex of patients with intractable epilepsy (IE) by immunohistochemistry, double-label immunofluorescence and immunoblotting. We compared these tissues against histologically normal anterior temporal lobes from individuals treated for post-trauma intracranial hypertension. We found that the IR was coexpressed with neuron-specific enolase (NSE) and that IR expression increased in the anterior temporal neocortex of epileptic patients. On the basis of the potential physiological effects of IR, our findings suggest that increased expression of the IR is a consequence of epileptic seizures and a cause of IE.

Maintenance of anti-inflammatory cytokines and reduction of glial activation in the ischemic hippocampal CA1 region preconditioned with lipopolysaccharide

2010-06-28

Abstract: Lipopolysaccharide (LPS) induces a strong immune response, and pretreatment with low dose of LPS suppresses the production of proinflammatory mediators. In the present study, we investigated the effect of LPS preconditioning on the delayed neuronal death in the gerbil hippocampal CA1 region after 5min of transient cerebral ischemia. LPS preconditioning showed neuroprotective effects against ischemic damage in the hippocampal CA1 region after ischemic insult: About 92% of neurons in the CA1 region survived in the LPS-treated ischemia group. LPS preconditioning maintained anti-inflammatory cytokines, such as interleukin (IL)-4 and IL-13, in pyramidal neurons in the CA1 region after ischemia/reperfusion. In addition, IL-4 and IL-13 protein levels in the CA1 region of the LPS-treated ischemia group were similar to the vehicle-treated sham group. We found that reactive gliosis was markedly attenuated in the CA1 region of the LPS-treated ischemia group compared to the vehicle-treated ischemia group using immunohistochemistry of glial fibrillary acidic protein for astrocytes, and ionized calcium-binding adapter molecule 1 and isolectin B4 for microglia. These results indicate that LPS preconditioning may provide neuroprotection in the ischemic hippocampal CA1 region via maintenance of anti-inflammatory cytokines and suppression of glial activation.

CPPD crystal deposition disease of the cervical spine: A common cause of acute neck pain encountered in the neurology department

Yoshiki Sekijima, Takuhiro Yoshida, Shu-ichi Ikeda — 2010-06-21

Abstract: Background: Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is one of the most common forms of crystal-associated arthropathy in the elderly. However, CPPD deposition on the cervical spine is less well known, and only a limited number of cases have been reported to date. Here, we report our recent clinical experience with CPPD crystal deposition disease of the cervical spine and describe the clinical features of this disease.Methods: Fourteen patients with clinically diagnosed CPPD crystal deposition disease of the cervical spine at our department during the period from January 2005 to December 2008 were analyzed retrospectively.Results: Patients ranged in age from 54 to 92 (mean±SD, 77.5±8.5). Chief symptoms of patients were acute posterior neck pain and fever. All patients had markedly restricted neck rotation. Serum CRP level was highly elevated in all patients (10.16±5.35mg/dL). Computed tomography of the cervical spine demonstrated linear calcific deposits in the transverse ligament of atlas (crowned dens syndrome) in all patients. Calcific deposits were also found in other periodontoid structures and the ligamenta flava in some patients. Posterior neck pain, fever, and increased serum inflammatory indicators were relieved within 1 to 3weeks by nonsteroidal antiinflammatory drugs (NSAIDs) or a combination of NSAIDs and prednisolone. Most of the patients were misdiagnosed as having other diseases before consultation.Conclusions: CPPD crystal deposition disease of the cervical spine is one of the most common underrecognized causes of acute neck pain in the neurology department, especially in elderly patients.

Augmentation of cholinesterases and ATPase activities in the cerebellum and pons-medulla oblongata, by a combination of antioxidants (resveratrol, ascorbic acid, alpha-lipoic acid and vitamin E), in acutely lindane intoxicated mice

Renu Bist, Devendra Kumar Bhatt — 2010-07-21

Abstract: In the present investigation neurotoxic effects of lindane and the protective potential of a combination of antioxidants against lindane-induced toxicity were evaluated in Swiss mice. The investigation was carried out on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and adenosine triphosphatase (ATPase) activities of the cerebellum and pons-medulla oblongata. Healthy mice, 7–8weeks old were administered acute dose of lindane (40mg/kg b.w.), antioxidants, both lindane and antioxidants, and vehicle in four separate groups, subcutaneously. Resveratrol (Res), ascorbic acid (C), alpha-lipoic acid (ALA) and vitamin E (E) were used in the combination for neuroprotection at the concentration of 5mg/kg b.w., 50mg/kg b.w., 20mg/kg b.w. and 50mg/kg b.w. respectively. Enzymatic activities were used as biochemical marker for manifestation of lindane-induced acute toxicity. Protective effects of antioxidants were also evaluated using the same parameters. Treatment of lindane to normal control animals resulted in a significant decrease in AChE, BChE and ATPase levels in crude homogenates of cerebellum and pons-medulla. Antioxidants treatment significantly increased the levels of enzymes. Critical difference (CD) of AChE, BChE and ATPase levels in various groups was found significant at 1% in cerebellum and pons-medulla both (i.e. P<0.01).

Atypical brain response to novelty in rural African children with a history of severe falciparum malaria

2010-06-21

Abstract: Plasmodium falciparum is the most common parasitic infection of the central nervous system causing neuro-cognitive deficits in 5–26% of paediatric cases. The burden cannot be reliably estimated because of lack of sensitive, culture-fair and robust assessments in rural settings. Auditory and visual brain event related potentials (ERPs) are used to compare novelty processing in children exposed to severe malaria with community controls. Fifty children previously admitted and discharged from Kilifi District Hospital with severe falciparum malaria were selected and compared with 77 unexposed agematched children. The results showed that up to 14% of children exposed to severe malaria had significantly different responses to novelty compared to unexposed children. Children exposed to severe malaria had smaller P3a amplitudes to novelty in both auditory [F (3, 119)=4.545, p=0.005] and visual [F (3, 119)=6.708, p<0.001] paradigms compared to unexposed children. In the auditory domain the differences in processing of novelty were not related to early component processing. The percentage of children with severe malaria showing impaired performance using ERPs is within the range previously reported using neuropsychological tests. The overall pattern suggests that severe malaria affects prefrontal and temporal cortices normally activated by stimulus novelty.

Stroke severity and residual flow determined by transcranial colour-coded ultrasound (TCCD) predict recanalization and clinical outcome during thrombolysis

2010-06-21

Abstract: Objective: To determine clinical, neuroradiological or ultrasonographic parameters associated with early recanalization and clinical outcome in patients treated with intravenous (IVT) or combined intravenous–intra-arterial (IVT–IAT) thrombolysis.Methods: From 2004 to 2007, all consecutive ischemic stroke patients admitted within a 3-hour window and who underwent thrombolytic therapy were reviewed. Degree of occlusion and recanalization during IVT was assessed by transcranial color-coded ultrasound (TCCD) using Thrombolysis In Brain Ischemia (TIBI) classification. According to our protocol, in case of recanalization (modification of TIBI grade≥1) after 30min of IVT, the procedure was maintained over 1h. When TIBI grade failed to improve after 30min, IVT was discontinued and IAT performed using the remaining tPA dose. The study endpoints were early recanalization defined as achievement of TIBI≥3 grade at 30min (for this endpoint all patients presenting a TIBI grade 3 at admission were excluded from the model) and clinical outcome at 3months assessed by the modified Rankin scale.Results: Seventy-one patients underwent either IVT (n=41) or IVT-IAT (n=30). Among all the variables, NIHSS and TIBI grades assessed at baseline were the only independent factors associated with early recanalization and clinical outcome. Furthermore, the combination of these two parameters was superior in predicting early recanalization and outcome to either one of them taken separately. An inverse correlation between NIHSS, TIBI grades and early recanalization was found: the lower the TIBI grade, the lower the probability to recanalize for any given NIHSS.Conclusion: Baseline NIHSS and TIBI grades were the only independent factors associated with early recanalization and clinical outcome. The combination of these two parameters was superior to each single variable in predicting the study endpoints and could therefore be used to improve the selection of patients for IVT or more aggressive therapies.

MELAS syndrome associated with both A3243G-tRNALeu mutation and multiple mitochondrial DNA deletions

2010-07-23

Abstract: The syndrome of mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS) is characterized clinically by recurrent focal neurological deficits, epilepsy, and short stature. The phenotypic spectrum is extremely diverse, with multisystemic organ involvement leading to isolated diabetes, deafness, renal tubulopathy, hypertrophic cardiomyopathy, and retinitis pigmentosa. In 80% of cases, the syndrome is associated with an AG transmission mutation (A3243G) in the tRNALeu gene of the mitochondrial DNA (mtDNA).We describe a woman with a unique combination of the MELAS A3243G mutation and multiple mtDNA deletions with normal POLG sequence. The patient presented with diabetes mellitus, sensorineural deafness, short stature, and mental disorientation. All her three children died in early adolescence.

Fluctuating neuromuscular transmission defects and inverse acetazolamide response in episodic ataxia type 2 associated with the novel CaV2.1 single amino acid substitution R2090Q

Nico Melzer, Joseph Classen, Karlheinz Reiners, Mathias Buttmann — 2010-07-21

Abstract: We report on a 51-year-old woman with episodic ataxia type 2 (EA2) and a novel CaV2.1 C-terminal single amino acid substitution (R2090Q). She had a 4-year history of acute episodes with ataxia, hemihypesthesia and hemicrania. Furthermore, fluctuating neuromuscular transmission abnormalities rarely described in patients with EA2 were clinically and electrophysiologically documented in this patient. Upon initiation of acetazolamide treatment she experienced a dose-dependent severe increase of attack frequency and severity along with a shorter attack duration, while she responded well to subsequent therapy with 4-aminopyridine.

N88S mutation in the BSCL2 gene in a Serbian family with distal hereditary motor neuropathy type V or Silver syndrome

2010-07-05

Abstract: Background: Distal hereditary motor neuropathy type V (dHMN-V) and Silver syndrome are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) gene or Seipin.Aim: To report the first Serbian family with a BSCL2 mutation showing variable expression within the family.Patients and methods: A 55-year-old woman presented with weakness of both hands at the age of 45. At age 47, she noticed distal muscle weakness and atrophy in her legs. Physical examination revealed atrophy and weakness of small hand muscles and mild atrophy and weakness of the lower limbs. There was generalized hyperreflexia with the exception of ankle reflexes which were diminished. Her 25year-old son had only stiffness of both legs at the age of 22. Physical examination revealed only generalized hyporeflexia. The third affected member in this family was her 55year-old cousin who showed a more prominent involvement of leg muscles with mild asymmetrical weakness of hand muscles and no pyramidal tract features.Results: In all three patients sensory nerve conduction velocities (NCV) were normal in all extremities. Compound muscle action potential (CMAP) amplitudes were markedly reduced in all patients. Concentric needle EMG showed evidence of chronic denervation in distal muscles. DNA sequencing of BSCL2 was performed and a heterozygous N88S missense mutation in BSCL2 gene was detected in all three patients.Conclusion: This report is further confirmation of phenotypic heterogenity due to the N88S mutation of BSCL2 gene in the same family.

Subclavian steal syndrome secondary to Takayasu Arteritis in a young female Caucasian patient

2010-07-22

Abstract: Subclavian steal syndrome (SSS) is most frequently described in Caucasians aged over 50years because of increased incidence of atherosclerosis in this population. Non-atherosclerotic etiologies of SSS are rare in Caucasians. We present a case of Subclavian Steal Syndrome secondary to Takayasu Arteritis (TA) in a 26year-old female Caucasian patient. The present case underscores that despite the very low incidence of TA in Caucasians (0.8/1,000,000), this large-vessel vasculitis of unknown etiology should always be considered in the differential diagnosis of subclavian steal syndrome in Caucasian women aged less than 40years.

Semantic dementia associated with mutation V363I in the tau gene

2010-07-05

Abstract: A 46-year-old woman who presented with prosopagnosia was clinically evaluated. Results of neuropsychological measures showed severe impairment in oral naming with anomia and a marked deficit in naming and recognition of famous faces. The clinical diagnosis was semantic dementia (SD). Genetic testing revealed a missense mutation V363I in exon 12 of the microtubule-associated protein tau (MAPT) gene. This is the description of an association between a mutation in the MAPT gene and a case of SD. The same mutation was recently described in a case of progressive non-fluent aphasia, but the prominent presenting feature in tau gene mutation cases is the behavioral variant of frontotemporal dementia, with typical symmetrical frontotemporal atrophy.

Capsular warning syndrome caused by middle cerebral artery stenosis

Jun Lee, Gregory W. Albers, Michael P. Marks, Maarten G. Lansberg — 2010-07-09

Abstract: The capsular warning syndrome is a term used to describe recurrent stereotyped lacunar transient ischemic attacks (TIAs). This syndrome is associated with a high risk of developing a completed stroke. The presumed mechanism for this syndrome is angiopathy of a lenticulostriate artery. We describe the case of a 33-year-old man who presented with the capsular warning syndrome who was successfully treated with angioplasty. The patient's capsular warning syndrome manifested as recurrent episodes of transient left hemiparesis. Symptoms recurred one to three times daily despite treatment with antithrombotics. Cerebral angiography demonstrated stenosis of the right middle cerebral artery (MCA) with decreased flow to a dominant lenticulostriate artery. Angioplasty of the right middle cerebral artery increased flow to the lenticulostriate artery and the TIAs resolved following the procedure. In select cases intracranial angioplasty, may be an effective treatment for patients with capsular warning syndrome.

High dose cyclophosphamide treatment in Marburg variant multiple sclerosis: A case report

Kenkichi Nozaki, Nada Abou-Fayssal — 2010-06-28

Abstract: Marburg variant multiple sclerosis (MS) is an acute, fulminant and monophasic variant of MS that usually leads to death within weeks to months. No consistently successful treatment is known. We describe a 26-year-old woman who developed acute and progressive motor and sensory deficits. Demyelinating disease was suspected based on brain and spinal MRI and cerebrospinal fluid results. Multiple treatments including corticosteroids, plasma exchange and intravenous immunoglobulin could not halt her clinical and radiological deterioration. She became near quadriplegic and developed motor aphasia. A diagnosis of Marburg variant MS was considered and she was given high dose cyclophosphamide (HiCy) at 50mg/kg/day for four consecutive days, followed by granulocyte colony-stimulating factor six days after the completion of the cyclophosphamide treatment. HiCy successfully induced neutropenia. She started to show a steady neurological improvement from day 17 of HiCy treatment. MR studies two months after HiCy treatment showed significant decrease in the size and enhancement of the lesions. Five months later she had minimal residual right-sided weakness and was able to ambulate without assistance. The great outcome seen in our case suggests that HiCy should be considered as a potential treatment for patients with Marburg variant MS who fail to respond to standard therapy.

Agnes Jani-Acsadi — 2010-07-26

Myasthenia Gravis, and related disorders affecting transmission across the neuromuscular junction, represent diagnostic and treatment challenges. Recent epidemiological studies have shown that disease prevalence has increased since the 1950s in the US (NIH, The National Women's Health Centre, 2004). This is partly due to heightened awareness, better diagnostic methods and improved therapies. Most treatments are costly and hospitalization often leads to need for intensive care, interventional procedures such as thymectomy and plasma exchange. These factors and patient disability put a significant emotional and economical burden on families and the health care system.

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2010-09-15

Note to Authors

2010-09-15