Glatiramer acetate in treatment-naïve and prior interferon-beta-1b-treated multiple sclerosis patients

Objective – This prospective, open‐label study evaluated the efficacy, safety, and tolerability of glatiramer acetate (GA) in treatment‐naïve relapsing–remitting multiple sclerosis (RRMS) patients and in patients who had previously received interferon‐β (IFN‐β)‐1b therapy. Methods – Two treatment cohorts were defined based on prestudy IFN‐β‐1b use. At entry, prior IFN‐β‐1b patients (n = 247) were older, had longer disease duration, and had higher mean Expanded Disability Status Scale (EDSS) scores, relapse rates, and ambulation indexes than treatment‐naïve patients (n = 558). Safety was assessed every 3 months and EDSS every 6 months for up to 3.5 years. Results – Overall, 247 treatment‐naïve and 107 prior IFN‐β‐1b patients discontinued before study end. Median GA treatment durations were 36 and 24 months in treatment‐naïve and prior IFN‐β‐1b patients, respectively. At last observation, annual relapse rates had declined by 75% in both cohorts (0.42 ± 0.84 and 0.34 ± 0.71 in treatment‐naïve and prior IFN‐β‐1b groups, respectively, P = 0.1482). Mean changes in EDSS were less than 0.5 in both cohorts, regardless of entry EDSS, at 12 and 18 months and at last observation. Conclusions – Prior IFN‐β‐1b treatment does not negatively influence the efficacy, safety, or tolerability of subsequent GA therapy. Switching to GA can benefit patients who discontinue IFN‐β therapy.     

Focal clinical and electroencephalographic features in patients with juvenile myoclonic epilepsy

Jayalakshmi SS, Srinivasa Rao B, Sailaja S. Focal clinical and electroencephalographic features in patients with juvenile myoclonic epilepsy.
Acta Neurol Scand: 2010: 122: 115–123.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – To identify prevalence and factors associated with occurrence of focal clinical and electroencephalogram (EEG) abnormalities in patients with juvenile myoclonic epilepsy (JME). Materials and methods – Clinical asymmetries in the seizures and focal EEG abnormalities were analyzed in 266 patients with JME. Results – All the patients had myoclonic jerks (MJ) and generalized tonic‐clonic seizures (GTCS); 56 (21%) had absence seizures. Asymmetry in clinical seizures was reported in 45 (16.9%) and focal EEG abnormalities were noted in 92 (45.5%) patients. Amplitude asymmetry or focal onset of generalized discharges was noted in 41 (44.6%) and independent focal EEG abnormalities in 30 (32.6%) patients. A statistically significant association was seen with the presence of GTCS and MJ (P = 0.007), a family history of epilepsy (P = 0.001) and drug resistance (P = 0.04) and the occurrence of focal EEG abnormalities. Conclusion – Patients with JME showed focal clinical and EEG features. These features should not be misinterpreted as indicative of partial epilepsy.     

Chronic inflammatory demyelinating polyradiculoneuropathy in children: characterized by subacute,predominantly motor dominant polyeuropathy with a favorable response to the treatment

Jo HY, Park M‐G, Kim D‐S, Nam S‐O, Park K‐H. Chronic inflammatory demyelinating polyradiculoneuropathy in children: characterized by subacute, predominantly motor dominant polyeuropathy with a favorable response to the treatment.
Acta Neurol Scand: 2010: 121: 342–347.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – Chronic inflammatory demyelinating polyradiculopathy (CIDP) is less well‐studied in children than in adults, probably due to its relative rarity. This study was performed in order to characterize the clinical features of CIDP in children. Materials and methods – Twenty‐eight patients with CIDP who were followed up for more than 1 year were included, and were divided into a child (n = 7, age <16) and an adult group (n = 21, age ≥16). Then, we have assessed the initial progression pattern, clinical course, and serial nerve conduction findings in each patient. Finally, differential features in child and adult group were analyzed. Results – Distinguishing features in the child group include subacute progression within less than 2 months, predominant motor system involvement in lower extremities, and marked improvement in response to immune modulating therapy. Our study also suggested that serial nerve conduction study may be useful in assessing the effectiveness of the treatment in children. Conclusions – Our study showed that children with CIDP have some distinguishing features from adults in terms of clinical course and response to treatment.     

Outcome of lamotrigine treatment in juvenile myoclonic epilepsy

Bodenstein‐Sachar H, Gandelman‐Marton R, Ben‐Zeev B, Chapman J, Blatt I. Outcome of lamotrigine treatment in juvenile myoclonic epilepsy.
Acta Neurol Scand: 2011: 124: 22–27.
© 2011 John Wiley & Sons A/S. Objectives – To determine the response rate of patients with juvenile myoclonic epilepsy (JME) to lamotrigine (LTG) and identify predictive factors for treatment response. Material and methods – Medical records of 62 patients with JME were reviewed for demographic, clinical, and EEG parameters. We determined clinical response to LTG and compared LTG responders with non‐responders. Results – There were 35 LTG responders (56%) and 27 non‐responders (44%). JME patients without generalized tonic clonic seizures (GTCS) responded better to LTG (P = 0.04). Valproic acid (VPA) failure because of adverse events rather than lack of efficacy (P = 0.069) and delay in diagnosis (P = 0.07) showed a tendency toward good response to LTG. Conclusions – LTG should be considered a drug of first choice for JME patients without GTCS. LTG as second‐line treatment after VPA failure seems more appropriate for those patients whose reason for VPA failure is poor tolerability rather than lack of efficacy.     

Primary Sjogren's syndrome: cognitive symptoms, mood, and cognitive performance

Segal BM, Pogatchnik B, Holker E, Liu H, Sloan J, Rhodus N, Moser KL. Primary Sjogren’s syndrome: cognitive symptoms, mood, and cognitive performance.
Acta Neurol Scand: 2012: 125: 272–278.
© 2011 John Wiley & Sons A/S. Objective – To investigate the relationships between self‐reported cognitive abilities, psychological symptoms and neuropsychological outcomes in PSS. Methods – Patients with Primary Sjogren’s syndrome (PSS) and healthy controls completed a comprehensive neuropsychometric battery and questionnaires: the Centers for Epidemiological Scale‐Depression, the Profile of Fatigue‐mental domain (Prof‐M) for cognitive symptoms, Fatigue Severity Scale, and the Short‐Form McGill Pain Questionnaire. Results – Female patients with PSS (N = 39) were similar to controls (N = 17) in estimated premorbid intellectual function, age and education. Depression (P = 0.002), cognitive symptoms (P = 0.001), fatigue (P = 0.000003), and pain (P = 0.024) scores were greater in the patient group. Patients with PSS demonstrated inferior performance relative to controls in psychomotor processing (P = 0.027) and verbal reasoning (P = 0.007). Patients with PSS with and without depression had similar performance on multiple tests, but depressed patients had significantly lower scores for executive function (P = 0.041). Cognitive symptoms correlated with verbal memory (P = 0.048), whereas pain correlated with executive function measures (Stroop, P = 0.017) and working memory (Trails B, P = 0.036). In the regression model, depression and verbal memory were independent predictors that accounted for 61% of the variance in cognitive symptoms. Conclusion – The Prof‐M is a simple self‐report measure which could be useful in screening PSS subjects who may benefit from detailed psychometric evaluation. Our results are consistent with the hypothesis that depression and verbal memory impairment are overlapping but independent aspects of neural involvement in PSS. While pain and depression are significant confounders of cognitive function in PSS, this study suggests that impaired verbal reasoning ability in PSS is not attributable to pain or depression.     

The relationship between depression and regional cerebral blood flow in Parkinson's disease and the effect of selegiline treatment

Melberg A, Örlén H, Raininko R, Entesarian M, Dahlqvist J, Gustavson KH, Dahl N. Re‐evaluation of the dysequilibrium syndrome.
Acta Neurol Scand: 2011: 123: 28–33.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives – To re‐evaluate middle‐aged Swedish patients diagnosed with dysequilibrium syndrome (DES) in childhood and to compare their clinical and neuroimaging features to DES with VLDLR gene mutations (DES‐VLDR). Materials and methods – Six patients from five families underwent neurological examination and magnetic resonance imaging (MRI) of the brain. Blood samples from the patients were screened for serum carbohydrate‐deficient transferrin (s‐CDT; disialotransferrin). The very‐low‐density lipoprotein receptor (VLDLR) gene was sequenced. Results – Five patients had non‐progressive cerebellar ataxia (NPCA), dysarthria and short stature. Mental retardation and strabismus, characteristic for DES‐VLDLR, were inconsistent among our patients. None of our patients had VLDLR mutations or MRI findings characteristic of DES‐VLDLR. MRI findings were variable from a normal cerebellum to marked cerebellar hypoplasia or atrophy and signal intensity changes. One patient was diagnosed with congenital disorder of glycosylation type 1a (CDG‐1a). Conclusions – DES was originally coined on mainly clinical grounds before MRI and specific genetic tests were available, both of which should be used to arrive at an appropriate diagnosis.     

Antidepressant medication exposure and 5‐HT1A autoreceptor binding in major depressive disorder

Objective: We have previously reported higher brain serotonin 1A (5‐HT_1A) autoreceptor binding in antidepressant‐naïve patients with Major Depressive Disorder (MDD) compared with healthy volunteers, and a decrease in binding in MDD after selective serotonin reuptake inhibitor (SSRI) treatment. This SSRI effect is also present in rodents administered SSRIs chronically. We therefore sought to determine the duration of antidepressant medication effects on 5‐HT_1A receptor binding after medication discontinuation. Methods: Positron emission tomography (PET) imaging with the 5‐HT_1A receptor radioligand [¹¹C]WAY‐100635 was performed in 66 individuals with current DSM‐IV MDD to examine relationships between 5‐HT_1A binding and time since most recent antidepressant treatment. All subjects were medication‐free for at least 2 weeks prior to scanning. Thirty‐two additional MDD comparison subjects were antidepressant naïve. Results: No differences in [¹¹C]WAY‐100635 binding were observed between antidepressant naïve and antidepressant exposed MDD groups in 13 a priori cortical and subcortical regions of interest, including raphe autoreceptors, assessed simultaneously in linear mixed effects models. Furthermore, [¹¹C]WAY‐100635 binding did not correlate with time off antidepressants in the antidepressant exposed patients considering these ROIs. The same results were observed when effects of treatment discontinuation of any psychotropic medication used to treat their depression was examined. Conclusion: These results indicate that any antidepressant‐associated downregulation of 5‐HT_1A autoreceptor binding reverses within 2 weeks of medication discontinuation. Since this effect is hypothesized to mediate the antidepressant action of SSRIs, and perhaps other antidepressants, it suggests that patients who need ongoing treatment may relapse rapidly when medication is discontinued. Moreover, 2 weeks appears to be a sufficiently long washout of antidepressant medications for a reliable measure of illness‐related binding levels.     

Effects of the abrupt switch from solution to modified-release granule formulation of valproate

Verrotti A, Nanni G, Agostinelli S, Tozzi Alleva E, Aloisi P, Franzoni E, Spalice A, Chiarelli F, Coppola G. Effects of the abrupt switch from solution to modified‐release granule formulation of valproate.
Acta Neurol Scand: 2012: 125: e14–e18.
© 2011 John Wiley & Sons A/S. Background – A new modified‐release (MR) granule formulation of valproate (VPA) has been recently developed for the treatment of children with epilepsy. It consists of tasteless microspheres that can be sprinkled on soft foods and easily swallowed. There are no data on the effectiveness of this formulation in pediatric age. Aim of the study – To evaluate the effects of the abrupt switch from solution to VPA MR granules in children undergoing chronic treatment. Methods – We enrolled children receiving VPA solution as sole or adjunctive therapy and switched them to MR granules at identical dosages. VPA blood level, treatment efficacy (clinical and EEG data), tolerability (adverse reactions), palatability, ease of administration, and compliance were evaluated before switching (T0) and after 4 weeks (T1). Results – Out of 112 enrolled children, 108 (96.4%) completed the evaluation. We observed no significant differences between the patients at T0 and T1 in VPA blood levels, treatment efficacy, tolerability, and compliance. MR granules were judged more palatable (P < 0.05) and easier to administer (P < 0.05) than solution by children and parents. At 6‐month follow‐up, all patients continued to use MR granules. Conclusion – Modified‐release granule formulation of VPA may be a reliable alternative to solution for its convenience of use.     

Cerebrospinal fluid metabolite and nigrostriatal dopaminergic function in Parkinson’s disease

Ishibashi K, Kanemaru K, Saito Y, Murayama S, Oda K, Ishiwata K, Mizusawa H, Ishii K. Cerebrospinal fluid metabolite and nigrostriatal dopaminergic function in Parkinson’s disease.
Acta Neurol Scand: 2010: 122: 46–51.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – To evaluate the association between cerebrospinal fluid (CSF) homovanillic acid (HVA) concentrations and nigrostriatal dopaminergic function assessed by positron emission tomography (PET) imaging with carbon‐11‐labeled 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)‐tropane (¹¹C‐CFT), which can measure the dopamine transporter (DAT) density, in Parkinson’s disease (PD). Methods – ¹¹C‐CFT PET scans and CSF examinations were performed on 21 patients with PD, and six patients with non‐parkinsonian syndromes (NPS) as a control group. Results – In the PD group, CSF HVA concentrations were significantly correlated with the striatal uptake of ¹¹C‐CFT (r = 0.76, P < 0.01). However, in the NPS group, two indices were within the normal range. Conclusions – In PD, CSF HVA concentrations correlate with nigrostriatal dopaminergic function. Therefore, CSF HVA concentrations may be an additional surrogate marker for estimating the remaining nigrostriatal dopaminergic function in case that DAT imaging is unavailable.     

Glial fibrillary acidic protein mutations in adult‐onset Alexander disease: clinical features observed in 12 Japanese patients

Yoshida T, Sasayama H, Mizuta I, Okamoto Y, Yoshida M, Riku Y, Hayashi Y, Yonezu T, Takata Y, Ohnari K, Okuda S, Aiba I, Nakagawa M. Glial fibrillary acidic protein mutations in adult‐onset Alexander disease: clinical features observed in 12 Japanese patients.
Acta Neurol Scand: 2011: 124: 104–108.
© 2010 John Wiley & Sons A/S. Objective – To clarify the clinical manifestations of adult‐onset Alexander disease (AOAD) in Japanese patients with glial fibrillary acidic protein (GFAP) gene mutations. Methods and materials – Twelve patients of AOAD with GFAP mutations detected in our centre were examined for neurological and magnetic resonance imaging (MRI) findings. Results – Major symptoms were pyramidal and bulbar signs. In addition, three patients presented abnormal behaviour and/or memory disturbance. Two of the three patients also had Parkinsonism and had been diagnosed with fronto‐temporal dementia or progressive supranuclear palsy until GFAP mutations were detected. Abnormalities of the medulla oblongata and cervical spinal cord were observed on MRI in all patients. Conclusions – Patients presenting with pyramidal and/or bulbar signs with abnormalities of the medulla oblongata and cervical spinal cord on MRI should be considered for GFAP analysis as this is the typical presentation of AOAD. Abnormal behaviour and cognitive disorders including deterioration of memory were rare symptoms but could be an obstacle to diagnosing Alexander disease.     

MR spectroscopy and atrophy in Gluten, Friedreich's and SCA6 ataxias

Hadjivassiliou M, Wallis LI, Hoggard N, Grünewald RA, Griffiths PD, Wilkinson ID. MR spectroscopy and atrophy in Gluten, Friedreich’s and SCA6 ataxias.
Acta Neurol Scand: 2012: 126: 138–143.
© 2011 John Wiley & Sons A/S. Background – Previous work using proton MR spectroscopy (¹H‐MRS) of the cerebellum in the ataxias suggested that ¹H‐MRS abnormalities and atrophy do not necessarily occur concurrently. Aims – To investigate the spectroscopic features of different types of ataxias. Methods – Using a clinical MR system operating at 1.5T, we performed ¹H‐MRS with a single voxel placed over the right dentate nucleus in 22 patients with gluten ataxia (GA), six patients with Friedreich’s ataxia (FA), six patients with spinocerebellar ataxia type 6 (SCA6) and 21 healthy volunteers. Atrophy of the vermis and hemispheres on standard MRI was rated by a neuroradiologist. Any interaction between atrophy and ¹H‐MRS was analysed for the three groups of patients and controls. Results – Patients with GA had significant atrophy of the vermis and hemispheres as well as abnormal ¹H‐MRS. Patients with SCA6 had more severe overall atrophy of the vermis and hemispheres, but relatively preserved N‐acetyl‐aspartate/creatine (NAA/Cr). The FA group showed significant atrophy of only the superior vermis with normal ¹H‐MRS. Conclusions – This study suggests that ¹H‐MRS of the cerebellum in patients with ataxia provides information in addition to the presence of atrophy. There are significant ¹H‐MRS differences amongst different types of ataxia with interesting correlations between atrophy and NAA/Cr.     

Two galantamine titration regimens in patients switched from donepezil

Engedal K, Davis B, Richarz U, Han J, Schäuble B, Andreasen N. Two galantamine titration regimens in patients switched from donepezil.
Acta Neurol Scand: 2012: 126: 37–44.
© 2011 John Wiley & Sons A/S. Objectives – In addition to inhibiting acetylcholinesterase, galantamine has allosteric‐modulating activity at nicotinic receptors. This may make galantamine an attractive option for patients starting treatment for Alzheimer’s disease (AD), but also for those who have not benefited from their current therapy. This study explored outcomes in subjects with AD transitioning from donepezil because of insufficient tolerability or efficacy. Materials and methods – Subjects previously receiving donepezil for mild‐to‐moderate AD were enrolled in a 12‐week randomized, open‐label study. After screening and a 7‐day washout, subjects were randomly allocated to galantamine fast (8 mg/week increments) or slow (8 mg/4 week) titration to 16–24 mg. Efficacy outcomes included the Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS‐cog/11), Mini‐Mental State Examination (MMSE), Clinician’s Interview‐Based Impression of Change – Plus Caregiver’s Input (CIBIC‐plus) and Alzheimer’s Disease Cooperative Study – Activities of Daily Living Inventory (ADCS‐ADL). Results – Eighty‐six of 89 patients (fast titration, n = 44; slow titration, n = 45) completed the study. At week 12, ADAS‐cog/11 score improved from screening by 2.6 and 0.6 in the fast‐ and slow‐titration arms, respectively (overall, ?1.6; P = 0.002). MMSE scores improved slightly in both arms (overall, +0.9; P = 0.002). Two‐thirds of patients had improvement or no change on the CIBIC‐plus at week 12. ADCS‐ADL scores did not change significantly from screening in either treatment arm. Galantamine was generally well tolerated; nausea (5.6%) and bradycardia (4.5%) were the most commonly reported adverse events. Conclusions – Patients in whom donepezil is ineffective or poorly tolerated may benefit from a switch to galantamine.     

(123) I]FP-CIT-SPECT asymmetry index to differentiate Parkinson's disease from vascular parkinsonism

Contrafatto D, Mostile G, Nicoletti A, Dibilio V, Raciti L, Lanzafame S, Luca A, Distefano A, Zappia M. [¹²³I]FP‐CIT‐SPECT asymmetry index to differentiate Parkinson’s disease from vascular parkinsonism.
Acta Neurol Scand: 2012: 126: 12–16.
© 2011 John Wiley & Sons A/S. Objectives – Differential diagnosis between vascular parkinsonism (VP) and Parkinson’s Disease (PD) is often difficult, due to the overlap in clinical presentation and the lack of specificity at neuroimaging. Aim of the study was to identify a possible reliable marker at SPECT imaging useful to distinguish the two conditions. Material and methods – We studied 20 PD, 20 VP and 20 essential tremor (ET) patients as control group, who had undergone a cerebral [¹²³I] FP‐CIT SPECT. A semiquantitative analysis was performed on DaTSCAN SPECT imaging and to establish the degree of asymmetry of the ligand uptake the Striatal Asymmetry Index (SAI) was used. Results – The binding of the ligand in the most affected side resulted significantly lower in VP than in ET patients but higher compared to PD patients. SAI was significantly higher in PD compared to VP (P < 0.001) and ET (P < 0.001) groups. We found that a cut‐off of SAI greater than 14.08 could differentiate PD from VP with a 100% specificity and a 50% sensitivity. Conclusions – SAI detected using [¹²³I]FP‐CIT SPECT can be used to differentiate VP and PD with a good degree of certainty.     

Minimizing pharmacodynamic interactions of high doses of lacosamide

Edwards HB, Cole AG, Griffiths AS, Lin B, Bean A, Krauss GL. Minimizing pharmacodynamic interactions of high doses of lacosamide.
Acta Neurol Scand: 2012: 125: 228–233.
© 2011 John Wiley & Sons A/S. Objectives – To determine whether pharmacodynamic interactions between high doses of lacosamide (400–800 mg/day) and concomitant sodium channel antiepilepsy drugs (AEDs) can be minimized in patients with drug‐resistant partial‐onset seizures. Materials and methods – Patients were rapidly initiated with high‐dose lacosamide (100 mg/week; increases to 400 to 800 mg/day), while simultaneously tapering concomitant sodium channel AEDs. Seizure frequency and side effects were evaluated at six time points: baseline, titration, 3, 6, 9 and 12 months. Results – Twenty‐three patients had a baseline median of 4 seizures/month with persisting partial‐onset seizures, despite previous treatment with an average of 6.8 AEDs. Mean decreases in monthly seizure frequency were as follows: 3 months 49.9% (P = 0.011), 6 months 55.4% (P = 0.010), 9 months 60.8% (P = 0.002) and 12 months 58.2% (P = 0.011). Most adverse events were mild CNS‐related symptoms and occurred transiently only during titration – there was no significant relationship (χ² < 1.5, P > 0.1) between lacosamide dose and the presence of side effects at 3, 6, 9 or 12 months. Conclusion – s – Drug‐resistant patients rapidly titrated to high doses of lacosamide with simultaneous tapering of traditional sodium channel AEDs had marked reduction in CNS‐related adverse events compared with patients treated in three previous pivotal trials that used fixed doses of concomitant AEDs.     

Is there progressive cognitive dysfunction in Sjögren Syndrome? A preliminary study

Martínez S, Cáceres C, Mataró M, Escudero D, Latorre P, Dávalos A. Is there progressive cognitive dysfunction in Sjögren Syndrome? A preliminary study.
Acta Neurol Scand: 122: 182–188.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objective – The aim of this study was to determine the progression of cognitive dysfunction in primary Sjögren Syndrome (SS). Methods – Twelve subjects with SS were compared with ten subjects with migraine and ten healthy controls on neuropsychological, mood and fatigue tests at baseline and 8 years later. Results – At follow‐up, SS subjects performed below subjects with migraine on the Continuous Performance Test (CPT) but did not differ on other tasks. Compared with controls, both clinical groups obtained lower scores on simple reaction time, patients with SS obtained lower scores on the Wisconsin Card Sorting Test (WCST) and patients with migraine performed below controls on the Benton’s Judgment of Line Orientation Test (JOLO). Clinical groups did not differ on cognitive changes over time, except that migraine subjects improved on verbal fluency. Compared with baseline, both SS and migraine patients were more impaired on simple reaction time, Trail Making Test part B, Stroop and JOLO. However, they showed higher scores on verbal and visual memory, WCST and CPT reaction time. SS also showed higher levels of depression and fatigue than migraine and controls, with no significant changes over time. Discussion – Preliminary evidence indicates some cognitive deficits in both SS and migraine following a pattern of fronto‐subcortical dysfunction without a significant cognitive decline over time.     

Impact of cladribine on soluble adhesion molecules in multiple sclerosis

Mitosek‐Szewczyk K, Stelmasiak Z, Bartosik‐Psujek H, Belniak E. Impact of cladribine on soluble adhesion molecules in multiple sclerosis.
Acta Neurol Scand: 2010: 122: 409–413.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Background – Soluble forms of vascular cell adhesion molecule‐1 (VCAM‐1), intracellular adhesion molecule‐1 (ICAM‐1) and E‐Selectin play a role in the regulation of blood–brain barrier damage and represent markers of the clinical course of multiple sclerosis (MS) and magnetic resonance imaging activity. We determined sICAM, sVCAM and sE‐Selectin concentrations in the cerebrospinal fluid (CSF) and serum of patients with remitting–relapsing multiple sclerosis before and after cladribine treatment as well as in a control group. Methods – We examined 17 patients diagnosed according to McDonald’s criteria. Thirteen healthy age‐matched subjects served as controls. The ELISA method was used to measure sICAM‐1, sVCAM‐1 and sE‐Selectin. Results – The concentration of sICAM and sE‐Selectin decreased in sera (difference between patients and controls was statistically significant, in the former P < 0.04, in the latter P < 0.0003) but not in the CSF of MS patients after cladribine treatment. Conclusions – The reduction in sICAM and sE‐Selectin concentrations after cladribine treatment indicates an immuno‐suppressive effect of the drug. The changes in levels of sICAM and sE‐Selectin after cladribine treatment reflect disease activity and indicate a reduction in the inflammatory reaction.     

Clinical,neuroimaging and neurophysiological features in addicts with manganese‐ephedrone exposure

Sikk K, Taba P, Haldre S, Bergquist J, Nyholm D, Askmark H, Danfors T, Sörensen J, Thurfjell L, Raininko R, Eriksson R, Flink R, Färnstrand C, Aquilonius S‐M. Clinical, neuroimaging and neurophysiological features in addicts with manganese‐ephedrone exposure.
Acta Neurol Scand: 2010: 121: 237–243.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – To identify biomarkers supporting the clinical diagnosis of manganism in patients several years after exposure to manganese (Mn). Methods – Neurophysiological examinations, magnetic resonance imaging (MRI), single‐photon emission computed tomography and fluorodeoxyglycose (FDG) positron emission tomography were performed in four former ephedrone addicts with extrapyramidal symptoms. Results – Peripheral nervous system was not affected. No patients had reduced uptake of ¹²³I Ioflupane in the striatum. MRI signal intensities were slightly changed in the basal ganglia. All patients showed a widespread, but not uniform, pathological pattern of FDG uptake with changes mainly located to the central part of the brain including the basal ganglia and the surrounding white matter. Conclusions – Presynaptic neurons in the nigrostriatal pathway are intact in Mn‐induced parkinsonism after prolonged abstinence from ephedrone. The diagnosis is principally based on clinical signs and the history of drug abuse.     

Development of a disability scale for myotonic dystrophy type 1

Contardi S, Pizza F, Falzone F, D’Alessandro R, Avoni P, Di Stasi V, Montagna P, Liguori R. Development of a disability scale for myotonic dystrophy type 1.
Acta Neurol Scand: 2012: 125: 431–438.
© 2011 John Wiley & Sons A/S. Objectives – Myotonic dystrophy type 1 (DM1) is a multisystem disorder. Many tests in the literature have evaluated single aspects of DM1 patients, mainly focusing on muscular impairment, without an overall quantification of the different disease‐specific neurological features. We developed and validated a new functional scale for DM1 patients based on neuromuscular impairment (NI) and disability. Materials and methods – Thirty‐three patients were tested in basal condition, 18 were re‐evaluated after therapeutic intervention with mexiletine, and 13 at one year follow‐up without treatment. The scale includes 21 ordinal items in four areas: neuropsychology, motricity, myotonia and daily life activities. We evaluated inter‐ and intra‐observer reliability (intraclass correlation coefficient, ICC and Spearman correlations, respectively), internal consistency (Cronbach’s alpha), external validity (Spearman correlations between each area and other clinical and objective measurements and scales), and sensitivity to clinical changes after treatment or at follow‐up. Results – Our analysis provided good results for inter‐observer agreement (ICC = 0.72–0.97), intra‐observer reliability, and internal consistency for all areas (Cronbach’s α > 0.73). Total score and single area subscores were significantly correlated to objective measurements, disease duration and multisystem involvement. Finally, the scale was sensitive to clinical changes disclosing a significant improvement after treatment in the items assessing myotonia, and also to disease progression showing a significant worsening in all areas but myotonia in untreated patients. Discussion – Our scale provides a new practical measure to evaluate NI and disability of DM1 patients. Further longitudinal studies are warranted to confirm its reliability in tracking disease progression and severity over a longer period of time.     

Serum somatostatin in early‐stage Parkinson’s disease

Shiraishi M, Kobayashi T, Watanabe H, Kamo T, Hasegawa Y. Serum somatostatin in early‐stage Parkinson’s disease.
Acta Neurol Scand: 2010: 121: 225–229.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – To compare levels of plasma digestive hormones in patients with and without nausea or vomiting during initial treatment of early‐stage Parkinson’s disease (PD). Methods – This was a 3‐week, open‐label, randomized study of treatment with an antiparkinson drug in untreated PD patients. We measured the levels of plasma digestive hormones before (baseline) and 3 weeks after administration of an antiparkinson drug. Results – Mean value of serum somatostatin at baseline was significantly increased in PD patients compared with the control group (P < 0.01). Serum somatostatin levels were significantly increased after treatment in subjects who experienced nausea or vomiting (P < 0.01). However, significant increase in serum somatostatin levels after treatment was not observed in PD patients without nausea or vomitting. Conclusion – Serum somatostatin in early‐stage PD patients before treatment was increased compared with healthy subjects. The nausea and vomiting induced by antiparkinson drugs may be related to uncontrolled somatostatin secretion through central vagus nerve dysfunction .     

Cerebrospinal fluid dynamics and long-term survival of the Strata valve in idiopathic normal pressure hydrocephalus

Lundkvist B, Koskinen L‐OD, Birgander R, Eklund A, Malm J. Cerebrospinal fluid dynamics and long‐term survival of the Strata^® valve in idiopathic normal pressure hydrocephalus.
Acta Neurol Scand: 2011: 124: 115–121.
© 2010 John Wiley & Sons A/S. Objective – Cerebrospinal fluid (CSF) dynamics and long‐term shunt survival of the Strata^® CSF shunt were evaluated in patients with idiopathic normal pressure hydrocephalus (INPH). Subjects and methods – Seventy‐two patients with INPH received a Strata^® valve. A CSF infusion test, neuroimaging and video recording of gait were performed at baseline and at 6 months (n = 68) after surgery. Long‐term shunt survivals were obtained from patient records. Results – The shunt survival at 1 year was 94% and at 3 years 92.5%. Forty‐nine patients (72%) had an improved gait. Two patients were improved despite non‐functioning shunts, indicating a possible placebo response. Nineteen patients were not improved at the 6‐month follow‐up. The shunt tests revealed a functioning shunt in 12; thus, unnecessary shunt revisions could be avoided. Seventeen patients showed a siphoning effect. Shunt revisions were made in six patients. Eight hygromas/subdural hematomas were found. Conclusions – The long‐term survival of the Strata^® valves was good, and a concern of complications is not a reason to exclude elderly with INPH from shunt surgery. Studies are needed to evaluate pros and cons of the anti‐siphon device. Using a CSF shunt test, unnecessary shunt revisions may be avoided.