Journal of the Neurological Sciences

Editorial Board

2010-03-15

The spectrum of neurological disorders in a Zambian tertiary care hospital

Omar K. Siddiqi, Masharip Atadzhanov, Gretchen L. Birbeck, Igor J. Koralnik — 2010-01-13

Abstract: Objectives: To define the spectrum of inpatient and outpatient neurological illness in a Zambian tertiary care facility where HIV is endemic.Methods: A retrospective period prevalence study of patients seen by the consulting neurologist between 1/2/06–12/20/06 at the University of Zambia's University Teaching Hospital (UTH).Results: 443 inpatients and 368 outpatients were seen during this period. Overall, 160 (19.7%) patients underwent HIV testing: 125 (15.4%) HIV+ and 35 (4.3%) HIV−. The other 651 (80.3%) patients were untested. The most common inpatient neurological diseases among HIV+ patients were infectious diseases 26 (38.8%), neuropathy/radiculopathy 10 (10.4%), cerebrovascular disease 6 (9.0%), and myelopathy 5 (7.5%). The most common inpatient neurological diseases in the general population were cerebrovascular disease 62 (16.5%), infectious diseases 47 (12.5%), neuropathy/radiculopathy 37 (9.8%), and seizures/epilepsy 27 (7.2%). In the outpatient population, the most common neurological illnesses in HIV+ patients were neuropathy/radiculopathy 18 (31.0%), cerebrovascular disease 8 (13.8%), dementia/neurodegenerative 8 (13.8%), and encephalopathy 7 (12.1%). Outpatients in the general population most commonly had headaches/cephalgias 60 (19.4%), movement disorders 47 (15.2%), neuropathy/radiculopathy 43 (13.8%), and seizures/epilepsy 39 (12.6%).Conclusions: HIV-infected individuals are a sizeable group among neurology patients in Zambia, and they are affected by a different disease spectrum than the general population. Infectious diseases make up the largest percentage of inpatient neurological illness. Non-infectious causes are responsible for the majority of outpatient neurological cases. Emphasis should be placed on treatment of both infectious and non-infectious neurological illnesses. The most common outpatient neurological conditions are symptomatically treatable with routinely available medications.

Accelerometry in persons with multiple sclerosis: Measurement of physical activity or walking mobility?

Madeline Weikert, Robert W. Motl, Yoojin Suh, Edward McAuley, Daniel Wynn — 2010-01-11

Abstract: Objective: Motion sensors such as accelerometers have been recognized as an ideal measure of physical activity in persons with MS. This study examined the hypothesis that accelerometer movement counts represent a measure of both physical activity and walking mobility in individuals with MS.Methods: The sample included 269 individuals with a definite diagnosis of relapsing–remitting MS who completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ), International Physical Activity Questionnaire (IPAQ), Multiple Sclerosis Walking Scale-12 (MSWS-12), Patient Determined Disease Steps (PDDS), and then wore an ActiGraph accelerometer for 7days. The data were analyzed using bivariate correlation and confirmatory factor analysis.Results: The results indicated that (a) the GLTEQ and IPAQ scores were strongly correlated and loaded significantly on a physical activity latent variable, (b) the MSWS-12 and PDDS scores strongly correlated and loaded significantly on a walking mobility latent variable, and (c) the accelerometer movement counts correlated similarly with the scores from the four self-report questionnaires and cross-loaded on both physical activity and walking mobility latent variables.Conclusion: Our data suggest that accelerometers are measuring both physical activity and walking mobility in persons with MS, whereas self-report instruments are measuring either physical activity or walking mobility in this population.

Asymmetric dimethylarginine (ADMA) as a possible risk marker for ischemic stroke

2010-01-11

Abstract: Background: Asymmetric dimethylarginine (ADMA) affects vascular function by blocking nitric oxide synthesis. We examined the relationship of ADMA concentration to vascular risk factors in subjects who have undergone annual medical check-up.Methods: ADMA concentration, lipid profile and vascular risk factors were assessed during an annual medical examination in 116 subjects (mean age 58.7years). Univariate and multivariate analyses were carried out to assess factors associated with ADMA concentration. ADMA concentration was also assessed in 50 age-matched patients with ischemic stroke.Results: Mean serum ADMA concentration was significantly higher in the ischemic stroke patients than the medical check-up subjects (0.461±0.076 versus 0.433±0.056μmol/l; P=0.022). Univariate analysis showed that ADMA concentration in the medical check-up subjects was significantly associated with age, hypertension, dyslipidemia, fasting blood glucose, total and LDL cholesterol concentrations. Multiple stepwise linear regression analysis showed that hypertension (β=0.25, P=0.008) and dyslipidemia (β=0.19, P =0.048) were significant independent determinants of ADMA concentration. ADMA concentration increased progressively with number of vascular risk factors, with a significant (P=0.001) difference between subjects with no risk factors and subjects with ≥2 risk factors.Conclusions: Serum ADMA concentration was significantly associated with vascular risk factors in subjects undergoing routine medical check-up. ADMA concentration warrants further examination as a possible marker of future development of ischemic stroke.

Methylation patterns of cell-free plasma DNA in relapsing–remitting multiple sclerosis

2010-01-11

Abstract: Background: There is growing interest for identification of new targets for biomarker development in multiple sclerosis (MS). The goal of this study was to compare the concentration and the methylation patterns of cell-free plasma DNA (cfpDNA) in patients with relapsing–remitting multiple sclerosis (RRMS) and healthy individuals.Methods: Three 30-patient cohorts were examined: patients with RRMS, in either remission or exacerbation, and healthy individuals as controls. Concentration of cfpDNA was determined using a standard fluorometric assay. Patterns of methylation in 56 gene promoters were determined by a microarray-based assay (MethDet-56). The data were analyzed to identify statistically relevant differences among the study groups.Results: The concentration of cfpDNA in patients with RRMS was four to eight-fold higher compared to healthy controls. Significant differences in cfpDNA methylation patterns were detected in all three comparisons: RRMS patients in remission versus healthy controls were recognized with 79.2% sensitivity and 92.9% specificity; RRMS patients in exacerbation versus healthy controls were recognized with 75.9% sensitivity and 91.5% specificity; and RRMS patients in exacerbation versus those in remission were recognized with 70.8% sensitivity and 71.2% specificity.Conclusion: Based on our findings, we conclude that patients with RRMS display unique disease- and state-specific changes of cfpDNA. Our findings are of clinical significance as they could be used in the development of potentially new biomarkers for MS. This is the first report in our knowledge describing such changes of cfpDNA in patients with MS.

Progression markers of Spinocerebellar Ataxia 2. A twenty years neurophysiological follow up study

2010-01-13

Abstract: Nerve conduction is profoundly affected in Spinocerebellar ataxia 2 (SCA2) even before the onset of the disease, but there is no information regarding its progression to the final stage of SCA2. In order to study the progression patterns of nerve conduction abnormalities in SCA2 we performed a prospective follow up evaluation of sensory and motor conduction in 21 SCA2 mutation carriers-initially presymptomatics- and 19 non-SCA2 mutation carriers during 20years. The earliest electrophysiological alterations were the reduction of sensory amplitudes in median and sural nerves, which could be found 8 to 5years prior disease onset and in the last 4years of the preclinical stage respectively. These abnormalities were followed by the increase of sensory latencies and decrease of conduction velocities. Sensory amplitudes progressively decreased during the follow-up clinical stage, rendering almost all patients with abnormal amplitudes and lack of sensory potentials, with faster progression rates in patients with larger CAG repeat lengths. Peripheral motor nerves showed the later involvement. These findings were used to define three distinct stages that describe the progression of the peripheral neuropathy. We suggest that sensory amplitudes could be useful biomarkers to assess the progression of peripheral nerve involvement and therefore to evaluate future clinical trials of therapeutic agents.

Vision impairment in tuberculous meningitis: Predictors and prognosis

2010-01-07

Abstract: Background: Vision impairment is a devastating complication of tuberculous meningitis. In the present study we evaluated the predictors and prognostic significance of vision impairment in tuberculous meningitis.Methods: In this study, 101 adult patients with tuberculous meningitis were evaluated for vision status and physical disability and were followed up for 6months. Contrast enhanced magnetic resonance imaging (MRI) was performed at baseline and 6months.Result: Out of 101 patients, 74 patients had normal vision and 27 patients had low vision or blindness at enrollment. Thirteen patients died during the study period. Out of 88 patients who survived at 6months, 68 patients had good vision, 11 patients had low vision and 9 patients had blindness. Predictors of vision deterioration were papilledema, cranial nerve palsies, raised cerebrospinal fluid protein (>1g/L), and presence of optochiasmatic arachnoiditis in MRI. Predictors of blindness, at 6months, were found to be papilledema, vision acuity ≤6/18, cranial nerve palsies, tuberculous meningitis stage II or III, raised cerebrospinal fluid protein (>1g/L), optochiasmatic arachnoiditis, and optochiasmal tuberculoma. At 6months, 27 patients had death or severe disability. Predictors of death or severe disability at 6months were vision acuity ≤6/18, cranial nerve deficits, hemiparesis, clinical stage II or III, and presence of infarct in MRI.Conclusion: Vision impairment occurred in one-fourth of patients with tuberculous meningitis. Principal causes of vision loss were optochiasmatic arachnoiditis and optochiasmal tuberculoma. Impaired vision predicted death or severe disability.

Incidence of rotational vertigo in supratentorial stroke: A prospective analysis of 112 consecutive patients

2010-01-06

Abstract: Background: Single cases with hemispheric, cortical or subcortical, ischemic lesions presenting with rotational vertigo (RV), that challenge the notion of infratentorial or peripheral generation of RV have been published, but the incidence of this symptom in a larger series is unknown. The aim of this study was to investigate whether acute hemispheric cerebrovascular lesions cause vertiginous sensations with particular emphasis on RV.Methods: A total of 112 consecutive stroke patients were assessed in a prospective single-center study over a 22-month inclusion period. Rotational or other vertiginous sensations were assessed using a structured 5-item questionnaire and patients with vertigo were further evaluated with Yardley's Vertigo Symptom Scale. All subjects underwent standard clinical neuro-ophthalmological and neuro-otological testing and data were correlated to imaging findings.Results: RV was absent among our patients. Few subjects reported non-rotational vertiginous sensations with stroke onset. These were mainly right-hemispheric strokes with concomitant subcortical leukoaraiosis.Conclusion: In this case series we did not find any patients with spinning sensations which is supportive of the dogma that supratenotrial lesions do not cause RV. Certain hemispheric stroke patterns, however, may be related to non-rotational dizziness.

The combination of elevated BNP and AF as a predictor of no early recanalization after IV-t-PA in acute ischemic stroke

2009-12-16

Abstract: Background and purpose: In acute stroke patients treated with intravenous tissue plasminogen activator (t-PA), early recanalization can improve patient outcome. Heart failure may result in reduction of brain perfusion, which limits the ability of the blood stream to wash out emboli. Brain natriuretic peptide (BNP) is used as a biological marker of heart failure. Most stroke patients with atrial fibrillation (AF) have elevated BNP levels. We investigated the relationships of plasma BNP levels before t-PA infusion and AF with early recanalization after t-PA infusion.Methods: Patients with a major brain artery occlusion were studied prospectively. MRAs were performed before and within 60min after t-PA infusion. The relationship between BNP levels before t-PA infusion and the presence of AF with early recanalization was examined.Results: Seventy-nine patients (49 men; mean age, 75.5±10.4years; ICA occlusion in 25 patients, M1 in 32, M2 in 13, PCA in 3, and BA in 6) were enrolled. Follow-up MRA within 60min after t-PA infusion revealed recanalization in 35 (44.3%) patients and no recanalization in 44 (55.7%). Patients with AF (57.1% vs. 75.0%, P=0.0294) and BNP>150pg/dl (39.0% vs. 73.7%, P=0.0019) less frequently had early recanalization than those without AF and with BNP≤150pg/dl. The combination of AF and BNP>150pg/ml was a useful predictor for no early recanalization (positive predictive value, 79.4%; negative predictive value, 62.2%; sensitivity, 61.4%; specificity, 80.0%).Conclusion: The presence of AF and elevated BNP was associated with no early recanalization after IV-t-PA therapy. We should need further study to ascertain its predictive ability.

Methionine sulfoximine, an inhibitor of glutamine synthetase, lowers brain glutamine and glutamate in a mouse model of ALS

2010-01-08

Abstract: In an effort to alter the levels of neurochemicals involved in excitotoxicity, we treated mice with methionine sulfoximine (MSO), an inhibitor of glutamine synthetase. Since glutamate toxicity has been proposed as a mechanism for the degeneration of motor neurons in a variety of neurodegenerative diseases, we tested the effects of MSO on the transgenic mouse that overexpresses the mutant human SOD1G93A gene, an animal model for the primary inherited form of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS). This treatment in vivo reduced glutamine synthetase activity measured in vitro by 85%. Proton magnetic resonance spectroscopy, with magic angle spinning of intact samples of brain tissue, showed that MSO treatment reduced brain levels of glutamine by 60% and of glutamate by 30% in both the motor cortex and the anterior striatum, while also affecting levels of GABA and glutathione. Kaplan–Meyer survival analysis revealed that MSO treatment significantly extended the lifespan of these mice by 8% (p<0.01). These results show that in the SOD1G93A model of neurodegenerative diseases, the concentration of brain glutamate (determined with 1H-MRS) can be lowered by inhibiting in vivo the synthesis of glutamine with non-toxic doses of MSO.

Facial emotion recognition and cerebral white matter lesions in myotonic dystrophy type 1

2009-12-14

Abstract: In order to investigate the cognitive and neurological bases of social cognitive impairment in myotonic dystrophy type 1 (DM1), we examined the facial expression recognition abilities and the cerebral lesions in a group of DM 1 (5 men, 4 women).We measured sensitivity to facial emotions and compared the findings with magnetic resonance image (MRI) findings evaluated using a semi-quantitative method.The DM1 patients showed lower sensitivity to disgusted and angry faces as compared to the healthy controls. The assessment of brain lesions revealed that more severe lesions occurred in the frontal, temporal, and insular white matters. Sensitivity to the emotion of disgust was negatively correlated with temporal lesions, and sensitivity to anger negatively correlated with frontal, temporal, and insular lesions.The results of this study indicate an association between lesions in the frontal, temporal, and insular subcortices and decreased emotional sensitivity to disgust and anger in DM1 patients. These areas are thought to play an important role in emotional processing in the normal brain. Our results suggest that social cognitive impairment in DM1 patients is attributable to impaired emotional processing linked to white matter lesions.

Compulsive habits in restless legs syndrome patients under dopaminergic treatment

Emmanuelle Pourcher, Sophie Rémillard, Henri Cohen — 2009-12-07

Abstract: Since the introduction of levodopa therapy and dopaminergic replacement therapy to abate symptoms of idiopathic Parkinson's disease, repetitive compulsive behaviors have been reported and are now considered to be drug-related response complications. As dopamine (DA) agonists are the licensed treatment in Restless Legs Syndrome (RLS), a survey was conducted to determine the extent to which patients with RLS present compulsive behaviors. The aim of this study was to investigate the relationship between DA agonists and the occurrence of motor or behavioral compulsions, stress, depression, and sleep disturbance in RLS patients. A questionnaire was mailed three times, at four-month intervals over a period of 8months to all patients of the Quebec Memory and Motor Skills Disorders Clinic diagnosed with RLS. In addition to recording all medication information for RLS treatment, patients were assessed on the International Restless Legs Syndrome Study Group Rating Scale (IRLS), the Beck Depression Inventory-II (BDI-II), the Sleep Scale from the Medical Outcomes Study (MOS) and on a visual analog scale for current level of stress. A section pertaining to hobby, mania, and compulsion was also included. Analyses are based on 97 out of 151 patients (64.2%) with RLS who returned the three questionnaires. Twelve patients (12.4%) on stable DA agonist therapy (average dose 0.52±0.59mg Pramipexole equivalent) developed a new compulsive behavioral repertoire. Eating (3 women, 1 man), buying food or clothes (2 women, 1 man), trichotillomania (1 woman, 1 man), and gambling (1man) were among the compulsions developed under DA treatment. In addition, two women presented new tic-like phenomena. In contrast to the RLS patients without compulsive behaviors (53 treated with DA agonist; 32 untreated), those with compulsive habits reported experiencing more stress, depression and sleep problems. Patients with RLS with mood and stress states may be at greater risk of developing compulsive behaviors while receiving standard dosage DA agonist treatment. These behaviors are clearly linked to short-term satisfaction and underline the role of dopaminergic mesolimbic stimulation in the reinforcement process of rewarding behavioral sequences.

A study of α1 antichymotrypsin gene polymorphism in Indian stroke patients

Bindu I Somarajan, J. Kalita, U.K. Misra, B. Mittal — 2009-12-04

Abstract: Objective: To evaluate the role of ACT gene polymorphism in primary spontaneous intracerebral hemorrhage (PSICH) and ischemic stroke (IS).Methods: 193 PSICH, 272 IS and 188 controls were included from the same geographical area. The demographic and clinical stroke risk factors were noted. PSICH was confirmed by CT and IS by MRI. The location of stroke and size were noted. ACT gene polymorphism was analyzed by polymerase chain reaction. The ACT genotype and allele frequency in PSICH, IS and controls were compared.Results: The age of the PSICH was 56.9±13years, IS 54±16.7years and controls 54.8±10years. 134 females were in study and 65 in control groups. In the controls the AA genotype was 30%, AT 51.1% and TT in 16% whereas these were 39.3%, 53% and 7.7% in PSICH and 34.6%, 53.3% and 12.1% in IS. The frequency of T allele in controls was 41.5%, PSICH 34.2% and IS 38.6%. There was no significant difference in genotype and allele frequency in PSICH, IS and controls as well as location and etiology of stroke.Interpretation: The ACT genotype and allele frequency are not different in Indian PSICH and IS compared to controls.

Refractory status epilepticus: A developing country perspective

2009-12-03

Abstract: Objective: To analyse the underlying causes, therapeutic response and outcomes of convulsive refractory status epilepticus (RSE).Methodology: This retrospective analysis was carried on 98 patients with RSE (age: 16.9±14.5years). All had received a combination of parenteral benzodiazepine and phenytoin or phenobarbitone followed by other anti-epileptic drugs (AEDs). The clinical, EEG, imaging features of convulsive RSE and long-term seizure outcome were analysed.Results: Seventy six patients had de novo RSE for the first time in life. The mean duration of RSE, before and during NICU admission was 3.4±3.2days and 2.9±2.4days respectively. The mean duration of NICU stay and mechanical ventilation was 17.4±14.5 was 14.4±12.8days respectively. The precipitating factors included viral fever — 13, AEDs stoppage — 7 and alcohol — 1. EEG was abnormal in 81.5% of patients. CT and MRI were abnormal in 63.4% and 82.3% respectively. Thirty-four patients died and compared to those surviving, patients were older, had lesser duration of NICU stay and elevated CSF protein. Dependence for activities of daily living (ADL) at discharge was: recovered — 29, mild to moderate — 13 and severe — 22. Seizure outcome in 64 patients after 43.5±58.2weeks were — seizure-free: 65.6%, one seizure: 21.8%, >1 seizure/month: 14.1%, and seizure recurrence requiring admission: 1.5%. After six and twelve months of follow up, the long-term seizure outcome were: seizure-free: 48.3% and 28.6%; one seizure: 27.6% and 38.1%; >1 seizure/month: 20.7% and 28.6%; and seizure recurrence requiring admission: 3.4% and 4.7% respectively. Among those survived 49 de novo RSE, about one-third developed post-SE symptomatic seizures after 30.1±54.4weeks.Conclusions: Seizures could still be controlled in two-thirds of patients with convulsive RSE. About 30% of patients achieved long-term seizure freedom.

Extrathymic malignancies in thymoma patients with and without myasthenia gravis

Jone Furlund Owe, Milada Cvancarova, Fredrik Romi, Nils Erik Gilhus — 2009-12-25

Abstract: Objective: The influence of myasthenia gravis (MG) on risk of cancer is uncertain. Using nationwide, comprehensive data, we investigated the association between MG and occurrence of extrathymic malignancies in thymoma patients, and also assessed the risk of consecutive extrathymic malignancies after thymoma diagnosis.Methods: Two hundred twelve thymoma patients were identified at the Cancer Registry of Norway between 1969 and 2005. Records on all extrathymic malignancies for these patients were supplied from the Registry's database. Comparisons were made between MG and non-MG patients and between thymoma patients and the general population.Results: The frequency of extrathymic malignancies was similar in MG and non-MG thymoma patients, and so was the survival after thymoma diagnosis. Extrathymic malignancies occurred in 10% of thymoma patients within 10years following the thymoma diagnosis. Thymoma patients had a significantly increased risk of developing an extrathymic malignancy compared to the general population. This was not linked to any specific kind of cancer. Thymoma morphology was not a significant predictor for an increased risk of consecutive cancer.Conclusions: The immunological process underlying MG does not influence the risk of cancer in thymoma patients. Thymoma patients have a significantly increased risk of extrathymic malignancies. This is an intrinsic effect, being unaffected by a coexisting autoimmune disease such as MG and not specific for any type of cancer. Screening for extrathymic malignancies in thymoma patients is probably not recommendable, but clinicians should be aware of the high rate of extrathymic malignancies occurring in thymoma patients.

Head trauma can initiate the onset of adreno-leukodystrophy

2009-11-30

Abstract: X-linked adreno-leukodystrophy and its adult variant, adrenomyeloneuropathy, are caused by mutations in ABCD1 that encodes a peroxisomal membrane protein of unknown physiological significance. In spite of identical mutations, they can have markedly divergent neurological and neuropathologic characteristics. Adreno-leukodystrophy classically presents in normal boys with mild neuropsychiatric features, which progress to frank neurological signs, the vegetative state and death in approximately three years. Adrenomyeloneuropathy typically affects young men with spastic paraparesis and sensory ataxia that can progress over decades. The neuropathologic correlate for adreno-leukodystrophy is severe inflammatory demyelination of posterior cerebral white matter, while a chronic distal axonopathy of spinal cord and peripheral nerve occurs in adrenomyeloneuropathy. Consequently, both modifier genes and environmental factors have been implicated in their pathogeneses. We report five cases of adreno-leukodystrophy whose onsets were initiated by moderate to severe head trauma, two of whom were conversions from adrenomyeloneuropathy. Their clinical courses were rapidly incapacitating, short (i.e., weeks to a few years) and fatal due to marked cerebral inflammatory demyelination. These cases, in concert with several previous reports, indicate that head trauma is one environmental factor that can have a profoundly deleterious effect on those genetically at risk for, or with milder clinical phenotypes of, this disease. Avoidance of potential head trauma and a rapid response to episodes of moderate to severe head trauma in this patient population seem prudent.

The association between cognitive impairment and quality of life in patients with early multiple sclerosis

2009-11-30

Abstract: Cognitive deficits are common in patients with multiple sclerosis (MS) and may be observed early in the course of the disease. Current knowledge about the association between cognitive impairment and health-related quality of life (HQOL) in patients with early MS is limited. We used a well-established battery of cognitive tests and standardized HQOL measures to examine the associations between overall and domain-specific cognitive performance and quality of life in patients with early MS. Ninety-two patients with CIS or MS diagnosed in the previous three years participating in the CLIMB Natural History Study underwent a neurologic examination, neuropsychological evaluation and quality of life assessment. Associations between cognitive scores and HQOL measures were examined. There were no differences between cognitively impaired versus unimpaired subjects on any of the HQOL measures. After controlling for depression, scores on tests of information processing speed were significantly associated with several measures of HQOL including physical well-being, fatigue, and social support. In all cases, correlations between HQOL and cognitive measures were mild. These findings were observed in patients with limited cognitive impairment and minimal physical disability. Our results suggest that cognitive remediation programs aimed at improving cognitive skills may also improve quality of life for patients with early MS.

α Pix enhances mutant huntingtin aggregation

2009-12-07

Abstract: Huntington's disease is caused by polyglutamine-expanded mutant huntingtin (muhtt), an aggregation-prone protein. We identified the Pak-interacting exchange factor (α Pix/Cool2) as a novel huntingtin (htt) interacting protein, after screening actin-cytoskeleton organization-related factors. Using immunoprecipitation experiments, we show that α Pix binds to both the N-terminal of wild-type htt (wthtt) and mutant htt (muthtt). Colocalization studies revealed that α Pix accumulates in muthtt aggregates. Deletion analysis suggested that the dbl homology (DH) and pleckstrin homology (PH) domains of α Pix are required for its interaction with htt. Overexpression of α Pix enhanced muthtt aggregation by inducing SDS-soluble muthtt–muthtt interactions. Conversely, knocking down α Pix attenuated muhtt aggregation. These findings suggest that α Pix plays an important role in muthtt aggregation.

Risk factors for idiopathic intracranial hypertension in men: A case–control study

2009-11-30

Abstract: Objective: To identify risk factors for idiopathic intracranial hypertension (IIH) in men.Design: Case–control study. A 96-item telephone questionnaire, answered retrospectively, with cases recalling at the age of their diagnosis and controls recalling at the age of their corresponding case's diagnosis.Setting: Outpatient clinics in two US tertiary care centers.Participants: The characteristics of 24 men with IIH were compared to those of 48 controls matched for sex, age, race, and World Health Organization body mass index (BMI) category.Main outcome measures: Two previously validated questionnaires: the ADAM (Androgen Deficiency in Aging Males) questionnaire for testosterone deficiency and the Berlin questionnaire for obstructive sleep apnea (OSA), embedded within the telephone questionnaire. Analysis with Mantel–Haenszel odds ratios and mixed-effects logistic regression models accounted for matching.Results: Cases and controls had similar enrollment matching characteristics. Although matching was successful by BMI category, there was a small difference between BMI values of cases and controls (cases: median 31.7, controls: median 29.9; p=0.03). After adjustment by BMI value, men with IIH were significantly more likely than controls to have a positive ADAM questionnaire for testosterone deficiency (OR: 17.4, 95% CI: 5.6–54.5; p<0.001) and significantly more likely to have either a positive Berlin questionnaire for OSA or history of diagnosed OSA (OR: 4.4, 95% CI: 1.5–12.9; p=0.03).Conclusions: Men with IIH are more likely than controls to have symptoms associated with testosterone deficiency and OSA. These associations suggest a possible role for sex hormones and OSA in the pathogenesis of IIH in men.

The novel radical scavenger IAC is effective in preventing and protecting against post-ischemic brain damage in Mongolian gerbils

2009-11-30

Abstract: The removal of pathologically generated free radicals produced during ischemia, reperfusion and intracranical hemorrhage seems to be a viable approach to neuroprotection. However, at present, no neuroprotective agent has proven effective in focal ischemic stroke phase III trials, despite the encouraging data in animal models. This study aimed to explore the effect of the brain penetrant low molecular weight radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) in neurological damage subsequent to ischemia–reperfusion injury in Mongolian gerbils. We examined the intraperitoneal effects of IAC on temporary bilateral common carotid artery occlusion (BCCO) by means of morphological and histological analysis of the hippocampus. Significant dose-dependent protective effects of IAC (1 to 10mg/kg b.w.) against neuropathological and morphological brain changes were seen when administered i.p. 1h before temporary BCCO in Mongolian gerbils. When administered up to 6h after BCCO, IAC actually reverses the neurodegenerative processes (e.g. hippocampal cell viability) induced by ischemia in a dose-dependent fashion. Data show that IAC is highly effective in protecting and preventing oxidative brain damage associated with cerebral flow disturbances. It is also effective even in late treatment of the insult, emphasizing its potential role for the management of ischemic stroke patients.

The progression of cognitive deterioration and regional cerebral blood flow patterns in Alzheimer's disease: A longitudinal SPECT study

2009-11-23

Abstract: Background and purpose: The progression of cognitive deterioration in patients with Alzheimer's disease (AD) is considerably variable. The ability to predict the progression rate is important for clinicians to treat and manage patients with AD. We examined the possible relationship between the rate of cognitive deterioration and regional cerebral blood flow (rCBF) patterns in patients with AD.Methods: We followed 48 patients with AD for an average of 37months. They were subsequently divided into the rapidly progressing group (n=24) and slowly progressing group (n=24) based on an annual Mini-Mental State Examination (MMSE) score change. Initial and follow-up rCBF were assessed using single photon emission CT (SPECT) and the SPECT data were analyzed by 3D-stereotactic surface projections.Results: At initial evaluation, the rapidly progressing group had greater rCBF deficits mainly in the parietotemporal and frontal regions, and left posterior cingulate than did the slowly progressing group. When compared with initial SPECT, follow-up SPECT showed a significant rCBF reduction in widespread regions, including parietotemporal and frontal lobes, of the rapidly progressing group, while showed in the scattered and small regions of hemispheres of the slowly progressing group.Conclusion: Our longitudinal SPECT study suggests a significant association between rCBF deficits in the parietotemporal, posterior cingulate, and frontal regions and subsequent rapid cognitive and rCBF deterioration.

Responsiveness of patient-based and external rating scales in multiple sclerosis: Head-to-head comparison in three clinical settings

2009-11-18

Abstract: Background: Patient-based rating scales and especially quality of life scales have received increasing attention as secondary outcome measures in multiple sclerosis (MS). Responsiveness to health-related change of quality of life scales is thus an important property when these measures are to be used successfully in clinical trials.Methods: We conducted an analysis of 3 cohorts of MS patients to examine responsiveness of the Hamburg Quality of Life Questionnaire for Multiple Sclerosis (HAQUAMS). One cohort consisted of patients from the outpatient clinic whose overall health status deteriorated over the course of one year (n=53), one study investigated two neurorehabilitation programs (n=20 each) and a third study investigated a low-level aerobic fitness training intervention (n=15).Results: The total score of the HAQUAMS and several subscales was found to be responsive in all three settings. In addition, we provide minimally important difference (MID) estimates based on anchor- and distribution-based methods for all scales of the HAQUAMS.Conclusions: The HAQUAMS is responsive to change in observational and intervention studies in MS in adequately powered trials.

Comparison of TMS and DTT for predicting motor outcome in intracerebral hemorrhage

2009-11-16

Abstract: Background: TMS (transcranial magnetic stimulation) and DTT (diffusion tensor tractography) have different advantages in evaluating stroke patients. TMS has good clinical accessibility and economical benefit. On the contrary, DTT has a unique advantage to visualize neural tracts three-dimensionally although it requires an expensive and large MRI machine. Many studies have demonstrated that TMS and DTT have predictive values for motor outcome in stroke patients. However, there has been no study on the comparison of these two evaluation tools. In the current study, we compared the abilities of TMS and DTT to predict upper motor outcome in patients with ICH (intracerebral hemorrhage).Methods: Fifty-three consecutive patients with severe motor weakness were evaluated by TMS and DTT at the early stage (7–28days) of ICH. Modified Brunnstrom classification (MBC) and the motricity index of upper extremity (UMI) were evaluated at onset and 6months after onset.Results: Patients with the presence of a motor evoked potential (MEP) in TMS or a preserved corticospinal tract (CST) in DTT showed better motor outcomes than those without (p=0.000). TMS showed higher positive predictive value than DTT. In contrast, DTT showed higher negative predictive value than TMS.Conclusions: TMS and DTT had different advantages in predicting motor outcome, and this result could be a reference to predict final neurological deficit at the early stage of ICH.

Prominent cauda equina involvement in patients with chronic inflammatory demyelinating polyradiculoneuropathy

2009-11-09

Abstract: In chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), it has not been well known which segment of the peripheral nerves, distal or proximal, is more often involved in electrophysiological examination. This study compares nerve conductions at proximal segments with those at distal segments in 11 patients with CIDP. To obtain cauda euqina conduciton time (CECT), compound muscle action potentials (CMAPs) were elicited by magnetic stimulation using a MATS coil from the abductor hallucis muscle. CECT was prolonged in 9 patients (81.8%), whereas the ankle–knee conduction was delayed in 4 (36.4%). The proximal segments are more frequently involved than the distal segments in this disorder.

Differential gene expression in chronic inflammatory demyelinating polyneuropathy (CIDP) skin biopsies

Grace Lee, Zhaoying Xiang, Thomas H. Brannagan, Russell L. Chin, Norman Latov — 2009-11-18

Abstract: Gene expression analysis previously identified molecular markers that are up-regulated in sural nerve biopsies from patients with chronic inflammatory demyelinating polyneuropathy (CIDP). To determine whether the same or additional genes are also up-regulated in skin, we applied gene microarray profiling and quantitative real-time PCR (qPCR) analysis to skin punch biopsies from patients with CIDP and controls. Five genes, allograft inflammatory factor 1 (AIF-1), lymphatic hyaluronan receptor (LYVE-1/XLKD1), FYN binding protein (FYB), P2RY1 (purinergic receptor P2Y, G-protein-coupled, 1), and MLLT3 (myeloid/lymphoid or mixed-lineage leukemia translocated to, 3), all associated with immune cells or inflammatory processes, were elevated in punch skin biopsies from patients with CIDP as compared to normal subjects or patients with Charcot–Marie–Tooth Type 1 (CMT1). The average fold change of the 5 genes over normal expression, as determined by qPCR, was significantly elevated in skin biopsies from patients with CIDP in comparison to CMT1 or diabetic neuropathy, and similar to that seen in Lyme disease. The findings indicate the presence of inflammatory changes in the skin of patients with CIDP.

Gene therapy using lactoferrin-modified nanoparticles in a rotenone-induced chronic Parkinson model

2009-11-12

Abstract: Background: Gene therapy is considered one of the most promising approaches to develop an effective treatment for Parkinson's disease (PD). The existence of blood-brain barrier (BBB) significantly limits its development. In this study, lactoferrin (Lf)-modified nanoparticles (NPs) were used as a potential non-viral gene vector due to its brain-targeting and BBB-crossing ability.Methods and results: The neuroprotective effects were examined in a rotenone-induced chronic rat model of PD after treatment with NPs encapsulating human glial cell line-derived neurotrophic factor gene (hGDNF) via a regimen of multiple dosing intravenous administration. The results showed that multiple injections of Lf-modified NPs obtained higher GDNF expression and this gene expression was maintained for a longer time than the one with a single injection. Multiple dosing intravenous administration of Lf-modified NPs could significantly improve locomotor activity, reduce dopaminergic neuronal loss, and enhance monoamine neurotransmitter levels on rotenone-induced PD rats, which indicates its powerful neuroprotective effects.Conclusion: The findings may have implications for long-term non-invasive gene therapy for neurodegenerative diseases in general.

Effect of long-term valproate monotherapy on bone mineral density in adults with epilepsy

2010-01-07

Abstract: Background: We evaluated the cross-sectional relationship of duration and dosage of valproate monotherapy on bone mineral density (BMD) in adult patients with epilepsy.Methods: The BMD at lumbar level (L2–L4) was measured in consecutive adult epileptic patients receiving long-term (≥2years) valproate monotherapy by dual energy X-ray absorptiometry (DXA). Blood samples were collected for total serum calcium, phosphorus, magnesium, 25-hydroxyvitamin D3 and parathormone. Osteopenia and osteoporosis were defined according to the World Health Organization operational BMD definition. Cross-sectional associations were evaluated using Spearman's correlation coefficient.Results: A total of 41 patients were studied (mean age 32.3±8.2years, 12 men, mean duration of valproate monotherapy 10.6±7.4years). Osteopenia was present in 24% of subjects, while no case of osteoporosis was documented. Duration and dosage of valproate monotherapy did not correlate with BMD. No association was documented between duration or dosage of valproate monotherapy and biochemical parameters.Conclusions: Duration of valproate monotherapy does not correlate with decreased BMD in adult patients with epilepsy. No case of osteoporosis was identified in patients treated with valproate for a mean period of more than ten years. These findings indicate that bone metabolism may not be affected by valproate monotherapy.

Pittsburgh compound B binding in poststroke dementia

2010-01-07

Abstract: We hypothesize that Pittsburgh compound B (PIB) binding is common in poststroke dementia (PSD) and that cognitive decline may be faster in PIB positive patients. We performed PIB positron emission tomography (PET) among 17 subjects: 10 PSD patients, 4 Alzheimer's disease (AD) patients, and 3 healthy controls. We also compared the rate of change in mini-mental state examination (MMSE) between PIB positive and negative patients. We detected AD-like PIB binding in 4 PSD patients (40%), all the AD patients, and 1 healthy control. The global PIB retention standardized uptake value (SUV) at 35–45min for PIB positive stroke patients was 1.67 (range 1.56–1.82), which was similar to the AD patients (1.65; range 1.46–1.88) and was lower than PIB negative patients (1.29, range 1.24–1.34). Mean annual MMSE decline for the 4 PIB positive patients was 2.9 and that for the 6 PIB negative patients was 1. This pilot study suggests that PIB PET is feasible for the evaluation of PSD and PIB binding may be common in PSD. Whether presence of PIB binding is associated with a more rapid cognitive decline in PSD requires further study to confirm.

An unusual cause of posterior fossa mass: Lhermitte-Duclos disease

2010-01-08

Abstract: Lhermitte-Duclos disease (LDD) (dysplastic cerebellar gangliocytoma) is a rare disorder of unknown pathogenesis, presenting with signs and symptoms resulting from obstruction of cerebrospinal fluid flow and mass effect in the posterior fossa. Magnetic resonance imaging is the diagnostic modality of choice allowing preoperative diagnosis with characteristic findings. Surgery is the choice of treatment. The typical histopathological findings of LDD are characterized by widening of the molecular layer, absence of the Purkinje cell layer and hypertrophy in the granule cell layer. Herein we report an adolescent girl with LDD diagnosed preoperatively by the conventional and advanced MR techniques.

Bilaterally symmetric cervical spondylotic amyotrophy: A novel presentation and review of the literature

2010-01-04

Abstract: Background: Cervical spondylotic amyotrophy (CSA) is considered a syndrome of (1) unilateral upper extremity weakness and atrophy, (2) affecting either the proximal or distal musculature, (3) without sensory impairment or lower extremity dysfunction.Aims of study: The authors report a novel case of bilaterally symmetric CSA with blurring of the proximal–distal distinction, discuss the pathophysiology, and review the literature.Methods: A 45year old man presented with a several year history of insidiously progressive bilaterally symmetric upper extremity weakness and wasting, profound in the proximal musculature and moderate to severe in the distal muscle groups.Results: Based on the clinical, neuroimaging and electrodiagnostic features, this patient harbors a more severe phenotype of the classical syndrome.Conclusion: The authors propose expanding the generally accepted definition of CSA to include this bilaterally symmetric form of disease, thereby minimizing diagnostic error or delay. Additionally, based on this case and a review of the literature, adherence to the proximal–distal distinction should be avoided since it is commonly blurred. Accurate diagnosis is crucial since this presentation mimics the motor neuron disease variant Vulpian–Bernhardt syndrome. The importance of early diagnosis is underscored by reports of significant improvement with timely surgical decompression.

Excessive daytime somnolence in spinocerebellar ataxia type 1

Dien Dang, David Cunnington — 2010-01-04

Abstract: Autosomal dominant spinocerebellar ataxias (SCAs) are progressive neurodegenerative disorders which result in dysfunction of the neuronal systems of the spinal cord, brainstem, and cerebellum. The manifestations of daytime somnolence and abnormal sleep behavior have been described in SCA type 3 (SCA3) and SCA type 6 (SCA6), but as yet have not been described in SCA type 1 (SCA1). We report two cases of sleep disturbance, fatigue and excessive daytime somnolence in individuals with SCA1 and their progress through several therapies. These case studies are unique as they describe excessive daytime somnolence and sleep abnormalities in SCA1.

Clinico-pathological findings in a patient with progressive cerebellar ataxia, autoimmune polyendocrine syndrome, hepatocellular carcinoma and anti-GAD autoantibodies

2010-01-08

Abstract: Objective: To report clinical and pathological findings of a patient with late onset insulin-dependent diabetes mellitus (IDDM), progressive cerebellar ataxia (PCA) and hepatocellular carcinoma (HCC).Patient: A 64-year-old woman, with a long lasting IDDM, progressively developed a severe cerebellar syndrome and died 2years after the onset of the symptoms for a systemic infection. Autoantibodies to antigastric parietal cell and anti-pancreatic islet cell resulted positive. Autopsy showed a selective loss of Purkinje cells in the cerebellum, with an increase of Bergmann glia and variable microglial proliferation; furthermore, it disclosed an HCC. GAD-Abs were detected both in serum and CSF.Conclusions: Clinical and experimental reports suggest a possible role of neoplastic cells in producing GAD-Abs. We postulate, in our case, that HCC could have been responsible for an overproduction of GAD-Abs, leading to the onset of PCA. Thus, GAD-Abs could be considered as a paraneoplastic marker in a subgroup of patients with PCA.

Triple A syndrome: A novel compound heterozygous mutation in the AAAS gene in an Italian patient without adrenal insufficiency

2010-01-06

Abstract: Allgrove syndrome (or triple A syndrome) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency and autonomic/neurological abnormalities. It is caused by mutations in the AAAS gene, located on chromosome 12q13. We describe a 42-year-old patient who presented with neuropathy and was found to have alacrima, achalasia, mild autonomic dysfunction with significant central and peripheral nervous system involvement. She was later diagnosed with oligosymptomatic triple A syndrome. Sequencing of the AAAS gene identified two heterozygous mutations within exon 14 and its donor splice site (p.L430F−c.1288C>T and c.1331+1G>T), one of which is novel. Allgrove syndrome should be suspected in patients with neurological impairment associated with two or more of the main symptoms (alacrima, achalasia or adrenal insufficiency).

Sisters with clinically mild encephalopathy with a reversible splenial lesion (MERS)-like features; Familial MERS?

Takuji Imamura, Jun-ichi Takanashi, Jun Yasugi, Hitoshi Terada, Akira Nishimura — 2009-12-30

Abstract: We first report sisters presenting with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS)-like features, i.e., mild and reversible neurological manifestations, and MRI finding of a reversible lesion with transiently reduced diffusion in the corpus callosum associated with symmetrical white matter. The distributions of the white matter lesions (more extensive) and Na levels (normal) were different from those reported for sporadic MERS patients (subcortical white matter close to the central sulci, and hyponatremia), which suggested that the pathophysiology of the sisters with MERS-like features might be different from that of sporadic MERS. Some genetic factors might be involved in MERS, especially in some patients with extensive white matter lesions.

Effects of electrical stimulation in vestibular cortex areas in humans

Christoph Best, Hermann Stefan, Ruediger Hopfengaertner, Marianne Dieterich — 2010-01-04

Abstract: The case of a patient with focal epilepsy is reported who underwent presurgical evaluation by stereotactic intracranial electroencephalographic (EEG) recording. A subdural semi-grid electrode, consisting of three multi-channel strip electrodes, was implanted over the temporal lobe and temporo-occipital region; one multi-channel depth electrode was applied towards the posterior insular cortex. During electrical stimulation and EEG monitoring eye movements were recorded by 3-D video-oculography. Stimulation of the medial temporal gyrus induced blurring of vision and horizontal nystagmus. Stimulation of the superior temporal gyrus with low intensities also induced blurring of vision and a similar nystagmus, whereas increased stimulus intensity elicited a nystagmus with horizontal, vertical, and torsional components. These findings support the hypothesis that the superior temporal gyrus is one of the regions of a multisensory network that plays a crucial role in the processing of vestibulo-ocular information.

Spinocerebellar variant of adrenoleukodystrophy with a novel ABCD1 gene mutation

Jie-Yuan Li, Chia-Chi Hsu, Chi-Ren Tsai — 2009-12-30

Abstract: X-linked adrenoleukodystrophy (X-ALD) shows a wide range of phenotypic expression, and clinical presentation as adult-onset spinocerebellar ataxia has been rarely reported. Here, we report a Taiwanese family with X-ALD. The proband, a 37-year-old man presented with dysarthria, cerebellar ataxia and mild spastic paraparesis, and had atrophy of cerebellum and upper cervical cord on MRI. One of his nephews, a 9-year-old boy had a classic childhood cerebral ALD phenotype. This family harbors a novel deletion of 1 base pair in exon 8 at nucleotide position 2245 (2245delA) in the ABCD1 gene. This is the first report of the 2245delA mutation presenting with a spinocerebellar variant of X-ALD.

Slowly progressive encephalopathy with hearing loss due to a mutation in the mtDNA tRNALeu(CUN) gene

2009-12-23

Abstract: Pathogenic mutations in the tRNALeu(UCN) gene of mitochondrial DNA (mtDNA) have been invariably accompanied by skeletal myopathy with or without chronic progressive external ophthalmoplegia (CPEO). We report a young woman with a heteroplasmic m.12276G>A mutation in tRNALeu(UCN), who had childhood-onset and slowly progressive encephalopathy with ataxia, cognitive impairment, and hearing loss. Sequencing of the 22 tRNA mitochondrial genes is indicated in all unusual neurological syndromes, even in the absence of maternal inheritance.

Extrapontine myelinolysis as presenting manifestation of adrenal failure: A case report

2009-12-18

Abstract: Background: Hyponatremia is a fairly common metabolic disorder. Hyponatremic myelinolysis is a relatively rare, life threatening complication with poorly understood pathophysiology, varied clinical manifestations and uncertain treatment. This case report highlights the range of clinical and imaging phenomena associated with hyponatremic myelinolysis.Methods: Case report.Result: A middle aged lady presented with an acute delirious state, hypotension and severe hyponatremia on a background of skin hyper-pigmentation and weight loss. Her clinical course evolved to an akinetic-rigid state and later to parkinsonism. Extensive investigations for recognizing a primary neurologic disorder, including brain MRI and CSF analysis were normal, though she had disseminated miliary tuberculosis involving multiple organs. Brain MRI changes characteristic of extrapontine myelinolysis appeared two weeks after the onset of symptoms. The patient recovered completely over several weeks.Conclusion: This case of hyponatremic extrapontine myelinolysis occurred as the presenting manifestation of adrenal failure secondary to disseminated tuberculosis. Extraponine myelinolysis is difficult to diagnose in the context of delayed brain MRI changes and can have a favorable outcome with modern management.

Siblings with the adult-onset slowly progressive type of pantothenate kinase-associated neurodegeneration and a novel mutation, Ile346Ser, in PANK2: Clinical features and 99mTc-ECD brain perfusion SPECT findings

2009-12-14

Abstract: Pantothenate kinase-associated neurodegeneration (PKAN), formerly known as Hallervorden–Spatz syndrome (HSS), is an autosomal recessive neurodegenerative disorder characterized by iron accumulation in the brain. Mutations in the pantothenate kinase 2 (PANK2) gene are known to be responsible for PKAN. Several studies have revealed correlations between clinical phenotypes and particular PANK2 mutations. The adult-onset slowly progressive type of PKAN with PANK2 mutations is very rare. In this report, we describe siblings with the adult-onset slowly progressive type of PKAN with a novel mutation, Ile346Ser, in PANK2. The siblings had the same mutation in PANK2 and had common clinical signs such as misalignment of teeth, a high arched palate, hollow feet, a slight cognitive decline, and an apparent executive dysfunction, although they showed different patterns of movement disorders. Thus, even if PKAN patients have identical mutations, it is likely that they will present with different types of movement disorders. Brain perfusion single photon emission computed tomography in both patients showed decreased regional cerebral blood flow in the bilateral frontoparietal lobes, the globus pallidus, the striatum, and around the ventriculus quartus. Cardiac uptake of [123I] meta-iodobenzylguanidine was normal in both patients. Analysis of genotype–phenotype correlations and the elucidation of mutational effects on pantothenate kinase 2 function, expression, and structure are important for understanding the mechanisms of PKAN.

Neuronal and glial tau pathology in early frontotemporal lobar degeneration-tau, Pick's disease subtype

2009-12-18

Abstract: Frontotemporal lobar degeneration-tau, Pick's disease subtype (PiD) is one of the major types of frontotemporal dementia, but its pathogenesis and disease mechanisms remain unclear. Here, we report a case of very early PiD. The patient was a 63-year-old healthy woman without dementia or any apparent psychosis. She was admitted to the hospital with multiple organ failure, and died three days later. The brain weighed 1050g and showed focal atrophy of the parahippocampal gyrus and right medial temporal lobe. Microscopically, neuronal loss and gliosis were limited to the atrophic areas. Surprisingly, Pick bodies (PiBs) and ballooned neurons were abundant throughout the bilateral temporal cortices, including the dentate gyrus. Cortical lamination of PiBs was predominant in the upper layer (layer II>VI), and the size of early PiBs tended to be smaller than that in severely affected areas. Numerous glial tau-positive inclusions (astrocytic inclusions, oligodendroglial coiled bodies, and threads) were found not only in the cerebral cortex but also in the temporal white matter. The neuropathological findings in this case suggest that PiB formation started long before the appearance of clinical symptoms and that PiB formation originating from small neurons may differ from other tau aggregations such as neurofibrillary tangles.

A syndrome of the dentate nucleus mimicking psychogenic ataxia

2009-11-18

Abstract: To date, cerebellar involvement in control of non-motor functions like cognition and emotion is increasingly well established. Current models suggest that motor and non-motor networks connecting the cerebellum with cortical areas operate independently in closed and segregated loops. Here, we report a 59-year-old female patient with a small cerebellar lesion that shows that cognitive activation can significantly influence cerebellar motor control. Surprisingly, this led to a clinical picture mimicking a psychogenic disorder. Similar to non-human primates, this case suggests that the human dentate nucleus consists of distinct cognitive and motor domains with additional somatotopical arrangement of the latter. Extending current models of cerebro-cerebellar interaction, this case further illustrates that there can be significant functional cross-talk between motor and cognitive cerebellar networks.

A novel splicing mutation (c.870+3A>G) in SPG4 in a Korean family with hereditary spastic paraplegia

2009-11-26

Abstract: Hereditary spastic paraplegia (HSP) is a group of genetically heterogenous neurodegenerative disorders characterized by progressive spasticity and weakness of both lower extremities. Herein, we report a novel splicing mutation (c.870+3A>G) in SPG4 in a Koran family with an autosomal dominant-inherited pure HSP. The mutation is located in intron 5, and results in a deletion of the 188bp-sized exon 5. It is likely that the exon 5 deletion leads to spastin dysfunction and cause the typical symptoms and signs of patients.

Wedge-shaped medullary lesions in multiple sclerosis

2010-01-07

Abstract: Multiple sclerosis (MS) is a heterogeneous disease with variable clinical features and magnetic resonance imaging (MRI) findings. We report four MS cases with unusual wedge-shaped lesions in the paramedian ventral medulla oblongata demonstrated on MRI. The clinical features and MRI characteristics of the medullary lesions suggest an impairment of venous drainage. We propose that the formation of these wedge-shaped lesions may be related to the pattern of venous drainage in the ventral medulla and raised venous pressure due to chronic cerebrospinal venous insufficiency which has recently been described in MS.

Assessing lesion morphology in MS: Why does this matter?

Massimo Filippi, Maria A. Rocca — 2010-01-11

Since the beginning of its application, magnetic resonance imaging (MRI) has shown to be extremely sensitive in revealing the presence of lesions in the white matter (WM) from patients with multiple sclerosis (MS) or suspected of having MS . Typically, MS lesions appear as areas of increased signal on dual-echo and fast-fluid-attenuated inversion recovery (FLAIR) scans. On T1-weighted scans, some of these lesions may enhance after gadolinium injection, either diffusely or ring-like, whereas others may appear as hypointense areas, which indicate that severe tissue destruction has occurred . Hyperintense lesions on T2-weighted scans can, however, be encountered in a variety of neurological conditions and as a result of aging . As a consequence, a large effort has been devoted to reach consensus on a set of criteria useful to define spatial and temporal dissemination of lesions – the diagnostic hallmarks of MS [] – and to define MRI-based red flags which might point to other conditions . From their seminal description, MRI features associated to MS have been identified: MS lesions on MRI scans of the brain are more frequently located in the periventricular regions, corpus callosum and infratentorial areas (with the pons and the cerebellum more frequently affected than the medulla and the midbrain) , are characterized by oval or elliptical shapes, have an uneven distribution across the two hemispheres (contrary to what typically happens in hereditary and metabolic WM disorders), and a variable evolution on serial MRI scans. In patients at presentation with a clinically isolated syndrome suggestive of MS, lesion characteristics, such as distribution, morphology and evolution, are usually assessed accurately with the ultimate aim of identifying imaging features which might contribute to the diagnostic work up. Conversely, once a diagnosis of MS is established, these aspects are frequently somewhat overlooked, except when atypical lesions form over the course of the years .

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2010-03-15