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Myasthenia gravis (MG) is an autoimmune disease, with immune reactivity against the post-synaptic endplate of the neuromuscular junction. Apart from symptomatic treatment with choline esterase blockers, many patients also require immunomodulatory treatment. Despite existing treatment options, some patients are treatment refractory. We describe a patient with severe MG refractory to corticosteroids, four oral immunosuppressants, cyclophosphamide, rituximab and bortezomib who was treated with autologous haematopoietic stem cell transplantation. Two years after this, the patient has significantly improved in objective tests and in quality of life and leads an active life. Diplopia is her only remaining symptom and she is completely free of medication for MG. We believe that autologous haematopoietic stem cell transplantation can be an effective therapeutic option for carefully selected cases of severe, treatment refractory MG.

Objective: The aim of this study was to characterize the levodopa and carbidopa plasma concentration in relation to blinded motor function ratings. This is a part of a study where a Multimodal motor Symptoms Quantification (MuSyQ) platform consisting of three different types of sensors were tested while evoking motor fluctuations with levodopa/car-bidopa (LD/CD) microtablets in fluctuating Parkinson’s disease (PD) patients. Background: Today, dose titration and chronic treatment largely relies on the patient’s subjective assessment of symptoms and clinicians’ assessment of patient status during a visit at the clinic. Methods: This was a single-center, open-label, single dose study in patients experiencing motor fluctuations. Patients were given 150% of their individual levodopa equivalent morning dose. Blood sampling and motor function testing were conducted for up to 6.5 hours at prepecified time points. The patients performed standardized motor activities for clinical rating in accordance with parts of the Unified Parkinson’s disease Rating Scale (UPDRS) and Unified Dyskinesia Rating Scale (UDysRS). Each test cycle was video recorded, and the video sequences were presented to three movement disorder specialists in a randomized order for blinded rating of UPDRS items and the treatment response scale (TRS). Concentration versus time profiles and the pharmacokinetics were compared with a study previously conducted in healthy subjects. Results: Nineteen patients, 14 male and 5 female, were included in the study. The individual LD/CD doses ranged between 110/27.5 mg to 410/102.5 mg. The concentration time profiles are similar to the LD/CD microtablet profiles reported in healthy subjects. The blinded video ratings managed to capture the most distinctive movements. Conclusions: This is the first pharmacokinetic study where patients received LD/CD microtablets. For patients fluctuating from ‘off’ to dyskinetic, the relationship between the plasma concentration and motor

In idiopathic Parkinson disease and atypical parkinsonian disorders, central dopaminergic and overall brain functional activity are altered to different degrees, causing difficulties in achieving an unambiguous clinical diagnosis. A dual examination using I-123-FP-CIT (I-123-N-omega-fluoropropyl- 2 beta-carbomethoxy-3 beta-(4-iodophenyl) nortropane, or I-123-ioflupane) SPECT and F-18-FDG PET provides complementary information on dopamine transporter (DAT) availability and overall brain functional activity, respectively. Parametric images based on a single, dynamic C-11-PE2I (N-(3-iodoprop-2E-enyl)-2 beta-carbomethoxy-3 beta-(4-methyl-phenyl) nortropane) scan potentially supply both DAT availability (nondisplaceable binding potential [BPND]) and relative cerebral blood flow (relative delivery [R-1]) at voxel level. This study aimed to evaluate the validity of C-11-PE2I PET against the dual-modality approach using I-123-FP-CIT SPECT and F-18-FDG PET. Methods: Sixteen patients with parkinsonian disorders had a dual examination with F-18-FDG PET and I-123-FP-CIT SPECT following clinical routines and additionally an experimental C-11-PE2I PET scan. Parametric BPND and R-1 images were generated using receptor parametric mapping with the cerebellum as a reference. T1-weighted MR imaging was used for automated definition of volumes of interest (VOI). The DAT VOIs included the basal ganglia, whereas the overall brain functional activity was examined using VOIs across the brain. BPND and R-1 values were compared with normalized I-123-FP-CIT and F-18-FDG uptake values, respectively, using Pearson correlations and regression analyses. In addition, 2 masked interpreters evaluated the images visually, in both the routine and the experimental datasets, for comparison of patient diagnoses. Results: Parametric C-11-PE2I BPND and R-1 images showed high consistency with I-123-FP-CIT SPECT and F-18-FDG PET images. Correlations between C-11-PE2I BPND and I-123-FP-CIT uptake ratios were

AIMS AND OBJECTIVES: To prospectively identify different coping strategies among newly diagnosed amyotrophic lateral sclerosis patients and whether they change over time and to determine whether physical function, psychological well-being, age and gender correlated with the use of different coping strategies. BACKGROUND: Amyotrophic lateral sclerosis is a fatal disease with impact on both physical function and psychological well-being. Different coping strategies are used to manage symptoms and disease progression, but knowledge about coping in newly diagnosed amyotrophic lateral sclerosis patients is scarce. DESIGN: This was a prospective study with a longitudinal and descriptive design. METHODS: A total of 33 patients were included and evaluation was made at two time points, one to three months and six months after diagnosis. Patients were asked to complete the Motor Neuron Disease Coping Scale and the Hospital Anxiety and Depression Scale. Physical function was estimated using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale. RESULTS: The most commonly used strategies were support and independence. Avoidance/venting and information seeking were seldom used at both time points. The use of information seeking decreased between the two time points. Men did not differ from women, but patients ≤64 years used positive action more often than older patients. Amyotrophic Lateral Sclerosis Functional Rating Scale was positively correlated with positive action at time point 1, but not at time point 2. Patients' psychological well-being was correlated with the use of different coping strategies. CONCLUSIONS: Support and independence were the most used coping strategies, and the use of different strategies changed over time. Psychological well-being was correlated with different coping strategies in newly diagnosed amyotrophic lateral sclerosis patients. RELEVANCE TO CLINICAL PRACTICE: The knowledge about coping strategies in early stage of the disease may he

PURPOSE: T cells are important in the immunopathology of immune-mediated peripheral neuropathies (PNP) and activated vitamin D regulates the immune response through increasing the amount of regulatory T cells. An association between vitamin D deficiency and polyneuropathy has been stipulated; hence we assessed whether patients with primary immune-mediated PNP have low vitamin D [25(OH)D] levels. METHODS: Plasma levels of 25(OH)D were analyzed in 26 patients with primary immune-mediated PNP, 50 healthy matched blood donors and 24 patients with motor neuron disease (MND). INCAT score was assessed in patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. ALSFRS-R score was applied to MND patients and the modified Rankin (mRankin) scale compared disability among patient groups. RESULTS: Mean 25(OH)D value in PNP patients was 40±16nmol/l, compared to 69±21nmol/l in healthy blood donors (p<0.001). MND patients had a higher mean 25(OH)D than PNP patients (59±26nmol/L; p=0.006) and comparable levels to healthy blood donors (p=0.15). Mean 25(OH)D value was not higher in PNP patients with pre-existing vitamin D3 supplementation of 800IU/day (N=6; 35±18nmol/L) than in unsupplemented PNP patients (42±16nmol). INCAT score ranged from 0 to 10 (mean 3.5) and ALSFRS-R ranged from 11 to 44 (mean 31). mRankin score was more severe in MND patients (mean 3.5) compared to PNP patients (mean 2.1). CONCLUSIONS: All patients with primary immune-mediated PNP were diagnosed with vitamin D deficiency and they had significantly lower 25(OH)D values than healthy control persons and MND patients. We suggest monitoring of vitamin D status in patients with autoimmune PNP, since immune cells are responsive to the ameliorative effects of vitamin D.

OBJECTIVE: Only 70-80% of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) respond satisfactorily to the established first-line immunomodulatory treatments. Autologous haematopoietic stem cell transplantation (AHSCT) has been performed as a last treatment resort in a few therapy-refractory cases with CIDP. We describe the results of AHSCT in 11 consecutive Swedish patients with therapy-refractory CIDP with a median follow-up time of 28 months. METHOD: Case data were gathered retrospectively for AHSCT treatments in 11 patients with CIDP refractory to the first-line immunomodulatory treatments, intravenous high-dose immunoglobulin, corticosteroids and plasma exchange and to one or more second-line treatments used in 10 of the 11 patients. RESULTS: The median Inflammatory Neuropathy Cause and Treatment (INCAT) score within 1 month prior to AHSCT was 6 and the Rankin score 4. Total INCAT and Rankin scores improved significantly within 2-6 months after AHSCT and continued to do so at last follow-up. The motor action potential amplitudes (CMAP) improved already within 4 months (median) after AHSCT. Three of the 11 patients relapsed during the follow-up period, requiring retransplantation with AHSCT in one. Eight of the 11 patients maintained drug-free remission upon last follow-up. AHSCT was safe but on the short term associated with a risk of cytomegalovirus (CMV) and Epstein-Barr virus reactivation, CMV disease, haemorrhagic cystitis and pancreatitis. CONCLUSIONS: Our results though hampered by the limited number of patients and the lack of a control group suggest AHSCT to be efficacious in therapy-refractory CIDP, with a manageable complication profile. Confirmation of these results is necessary through randomised controlled trials.

OBJECTIVE: The aim was to elaborately describe individual pharmacokinetic-pharmacodynamic profiles in patients with difficult-to-treat dyskinesias treated with levodopa/carbidopa intestinal gel infusion. METHODS: A nonrandomized, partly blinded, investigator-initiated trial was conducted in 5 patients with idiopathic Parkinson disease who were difficult to keep in "on" state without dyskinesia. Levodopa/carbidopa intestinal gel (Duodopa) doses of 80% to 120% of individually and clinically optimized dosage were infused during five 4-hour periods. Pharmacokinetic profiling, blinded assessment of video recordings, and objective movement analysis were applied every 20 to 30 minutes. RESULTS: Individual correlations between plasma levodopa concentrations and corresponding motor scores 20 to 30 minutes after the sampling time were significant in all patients (P < 0.05 and P < 0.001). Motor scores were generally stable during the 4-hour periods. The objective test revealed that motor performance was faster the more dyskinetic the patients were. Mean individual Treatment Response Scale scores were positive in 24 of the 25 steady-state periods. Dystonia was always combined with choreic dyskinesias. CONCLUSIONS: Motor response from different doses of levodopa/carbidopa intestinal gel is in a broad sense predictable even in dyskinetic patients although major interindividual differences in dose requirement, plasma levels, and motor response are found. That motor performance was faster the more dyskinetic the patients were implies that motor performance may be better with moderate dyskinesia than with mild dyskinesia. This may explain why patients with persistent dyskinesias choose to keep their doses above the dyskinesia threshold. There is no ideal therapeutic window in such patients, but levodopa infusion offers stable motor response.

Background and purpose: Catechol-O-methyltransferase inhibitors may be used to decrease levodopa requirement. The objective was to investigate whether the levodopa/carbidopa intestinal gel infusion dose can be reduced by 20% without worsening of motor fluctuations and levodopa concentration stability when oral catechol-O-methyltransferase inhibitors are added. Methods: A short-term, randomized, partly blinded, crossover, investigator-initiated clinical trial was performed, with levodopa/carbidopa intestinal gel combined with oral entacapone and tolcapone on two different days in 10 patients. The primary outcome measure was difference in coefficient of variation of levodopa in plasma between levodopa/carbidopa, levodopa/carbidopa/entacapone, and levodopa/carbidopa/tolcapone. The secondary outcome measures other pharmacokinetic variables, patient-reported outcome, and blinded analysis of motor performance. Results: Variation of plasma levodopa concentrations did not differ significantly between the treatments. The treatments did not differ regarding motor performance. Levodopa concentrations were significantly higher using tolcapone. Concentrations of the metabolite 3-O-methyldopa decreased gradually during catechol-O-methyltransferase inhibition. Conclusions: According to this small, short-term pilot study, oral catechol-O-methyltransferase inhibitors administered in 5-h intervals may be useful in cases where levodopa/carbidopa intestinal gel dose reduction is wanted. Stability of plasma levodopa levels is not significantly altered, and off-time is not increased when decreasing the levodopa/carbidopa intestinal gel dose by 20%. Rather, the dose should probably be decreased more than 20%, especially under tolcapone co-treatment, to avoid increased dyskinesias with time.

BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder. Vitamin D has important roles both in the autoimmune response and in skeletal muscles. We determined the levels of 25-hydroxy vitamin D [25(OH)D] in patients with MG and in healthy subjects to determine whether vitamin D deficiency is present in MG and whether vitamin D supplementation has beneficial effects on fatigue. METHODS: Plasma levels of 25(OH)D were analyzed in 33 patients with MG (22 males; mean age, 58 years) and in 50 healthy age- and sex-matched blood donors, without vitamin D3 medication. MG composite score (MGC) assessed fatigue. 13 patients with MG without previous vitamin D3 supplementation were started on vitamin D3 supplementation (cholecalciferol) 800 IU/day, with a follow-up examination after 2.5-10 months (mean, 6 months). RESULTS: Patients with MG without pre-existing vitamin D3 supplementation (N = 16) had a mean MGC of 4.5 and lower plasma 25(OH)D levels (mean, 51 ± 19 nM) than healthy controls (69 ± 21 nM) (P = 0.017). Seventeen patients had pre-existing vitamin D3 supplementation, because of corticosteroid treatment, and their mean 25(OH)D was 79 ± 22 nM and mean MGC was 5.5. In the 13 patients who received cholecalciferol, 25(OH)D was overall increased at follow-up with 22% (P = 0.033) and MGC score improved with 38% (P = 0.05). CONCLUSIONS: Plasma 25(OH)D levels are significantly lower in patients with MG compared with healthy controls. As vitamin D has beneficial effects on the autoimmune response and on fatigue score in patients with MG, we suggest monitoring this parameter in patients with MG and supplementation with vitamin D3 when 25(OH)D levels are low.

Artikelns engelska titel i PubMed:[Inflammatory polyneuropathies can be treated successfully].

Andelen äldre ökar i populationen, och härav följer att ett ökande antal patienter med Parkinsons sjukdom kommer att genomgå operation och anestesi. Parkinsonpatienter behandlas med farmaka som potentiellt interagerar med perioperativt använda läkemedel. Abrupt perioperativ utsättning av antiparkinsonläkemedel ökar risken för försämring av grundsjukdomen och för neurologiska komplikationer ("malingt syndrom"). Parkinsonpatienter har inte sällan autonom dysfunktion, som kan komplicera det perioperativa förloppet. Andra sjukdomar är vanliga i denna patientgrupp. Det är viktigt att planera det perioperativa förloppet noggrant, likaså att fortsätta med antiparkinsonmedicinering under hela det perioperativa förloppet. Det finns idag ingen evidens för att en viss anestesimetod är att föredra framför en annan för denna patientgrupp. Regimen måste individualiseras och hänsyn tas till patientens grundmedicinering, grad av parkinsonkomplikationer och ingreppets natur.

BACKGROUND AND PURPOSE: The characteristics of levodopa dosing are not well described in the literature. The aims were to investigate the use of levodopa in a nationwide Swedish survey and to study the characteristics of low-dose and high-dose patients with Parkinson's disease (PD) in a university hospital. METHODS: Patients with >or= 1 and >or= 2 purchases of levodopa during 2007 were selected from the prescribed drug register. Daily levodopa doses were estimated. Records of 504 patients with PD who visited the neurology clinic at Uppsala University Hospital during 2006-2007 were examined to select a low-dose group (< or = 400 mg levodopa daily, n = 21) and a high-dose group (>or= 1200 mg daily, n = 26) with at least 5 years of PD duration. RESULTS: In total, 33 534 levodopa users with > or = 1 levodopa purchase were found. Daily levodopa dose range was large; median daily dose was 465 mg for men and 395 mg for women (P < 0.0001). Almost half (46%) of the patients used < 400 mg levodopa daily. Significantly, more men were treated with doses >or= 1200 mg daily. Dose and age correlated negatively (P < 0.0001). Patients with high dose at 5 years PD duration continuously increased their dosage the following years, whereas low-dose patients did not. The occurrence of dyskinesias was about the same in both groups despite the large difference in levodopa dose. CONCLUSIONS: We conclude that the levodopa requirement in PD ranges considerably, and that men use higher levodopa dose than women. Levodopa requirement is constant during the progression of the disease in low-dose patients but increases in high-dose patients.

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 (123)I 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.

BACKGROUND: Motor fluctuations in patients with advanced Parkinson's disease may be successfully treated with subcutaneous apomorphine infusion or intraduodenal levodopa/carbidopa infusion. No comparative trials of these two alternatives were performed. AIMS OF THE STUDY: We present a subanalysis from a randomized crossover clinical trial where levodopa infusion as monotherapy was compared with any other combination of pharmacotherapy in fluctuating patients. Four patients used apomorphine infusion and oral levodopa in the comparator arm. The results of these four patients are presented in detail. METHODS: The duration of the trial was 3 + 3 weeks. Patients were video-recorded half-hourly on two non-consecutive days of both treatment arms. Blinded video ratings were used. Patient self-assessments of motor function and quality-of-life (QoL) parameters were captured using an electronic diary. RESULTS: Ratings in moderate to severe "off" state ranged 0-44% on apomorphine infusion and 0-6% on levodopa infusion. Moderate to severe dyskinesias were not recorded in any of the treatments. QoL was reported to be improved in all patients on duodenal levodopa infusion. CONCLUSIONS: Monotherapy with duodenal infusion of levodopa was more efficacious and brought greater QoL than combination therapy with apomorphine infusion in these fluctuating patients.

Disorders affecting the postsynaptic side of the neuromuscular junction include autoimmune myasthenia gravis (MG) as well as some of the congenital myasthenic syndromes (CMS). Lambert-Eaton myasthenic syndrome (LEMS) is an acquired autoimmune neuromuscular disorder in which autoantibodies are directed against the presynaptic calcium channels. Here we describe two monozygous twin brothers: case 1 was diagnosed with an indeterminate form of acquired postsynaptic neuromuscular junction defect at age 32 and case 2 with LEMS at age 47. Case 1 presented clinically with mild generalized myasthenic weakness, neurophysiological examination revealed disturbed neuromuscular transmission along with probable myositis and serum analysis regarding antibodies against the acetylcholine receptor and muscle-specific tyrosine kinase was negative. Case 2 presented with proximal muscle fatigue accompanied by areflexia at rest and antibodies against the P/Q-type voltage-gated calcium channels were present. Neurophysiologically, case 2 had reduced baseline compound motor action potential amplitudes on neurography, decrement on low-frequency repetitive nerve stimulation (RNS) and pathological increment on high frequency RNS. To our knowledge this is the first case report of its kind and adds an intriguing contrast to the more common diagnosis of CMS in monozygous twins.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterised by the occurrence of symmetrical weakness and sensory impairment in arms and legs. The course is relapsing or chronic and progressing. CIDP is considered to be an autoimmune disease, which is supported by the beneficial response to immunomodulating therapies in most patients. We report on a patient with CIDP who has been in remission for more than 3 years after treatment with high dose cyclophosphamide and autologous blood stem cell transplantation in CIDP on two occasions.

Introduction - Patients with multifocal motor neuropathy (MMN) usually respond to intravenous immunoglobulin (IVIG), but because of the short-lasting effect the treatment must be given repeatedly. Remission after treatment with high-dose cyclophosphamide has recently been reported in one patient refractory to IVIG. Case report - Here we report on a patient who responded to IVIG, but temporarily deteriorated dramatically after treatment with high-dose cyclophosphamide and autologous blood stem cell transplantation. Today the situation is the same as before the treatment with cyclophosphamide and blood stem cell transplantation, i.e. IVIG is given every 4 weeks. Conclusion - Our patient did not benefit from the treatment with high-dose cyclophosphamide and autologous blood stem cell transplantation. The effect of treatment with high-dose cyclophosphamide in MMN seems to be difficult to predict and that should be paid attention to if this type of treatment is considered.