ABSTRACT
BACKGROUND: The prophylactic treatment of migraine includes anticonvulsant drugs such as valproic acid and topiramate. However, these substances are often poorly tolerated by migraine patients. So far levetiracetam has hardly been studied as an episodic migraine prophylactic agent in adults. OBJECTIVE: To perform a prospective pilot study for the evaluation of the efficacy and tolerability of levetiracetam in the prophylactic treatment of episodic migraine. METHODS: Fifty patients with episodic migraine were enrolled in this prospective, open label study. After a baseline period of four weeks, patients received 1,000 mg (starting dose 500 mg) bid levetiracetam for 12 weeks. Migraine frequency and accompanying symptoms were recorded in a headache diary. The primary endpoint was the comparison of attack frequency during the baseline with attack frequency during the last four weeks of treatment (treatment period 3). RESULTS: In the Intent-To-Treat analysis, 46% of the patients had a migraine reduction of more than 50% in the third period as compared to the baseline period. The mean number of migraine attacks decreased from 5.2 +/- 2.1 (baseline) to 3.4 +/- 2.7 (period 3). The most frequently reported side effects were somnolence, nausea, and weight gain; all were mild and transient. In a post-hoc comparison, responders to levetiracetam had significantly less migraine attacks at baseline and had significantly more often migraine with aura. CONCLUSION: The data suggest that levetiracetam has some potential in the prophylactic treatment of episodic migraine which seems, however, to be not superior to that of other anticonvulsant drugs. Levetiracetam was well tolerated and showed better efficacy in patients with migraine with aura and in less affected migraine patients. A larger placebo-controlled, double-blind study in adults seems justified on the basis of these data.
Subject(s)
Levetiracetam , Migraine Disorders , Adult , Anticonvulsants/therapeutic use , Double-Blind Method , Humans , Levetiracetam/therapeutic use , Migraine Disorders/drug therapy , Migraine Disorders/prevention & control , Migraine with Aura/drug therapy , Pilot Projects , Prospective Studies , Topiramate/therapeutic use , Treatment Outcome , Valproic Acid/therapeutic useABSTRACT
OBJECTIVE: Neuromyelitis optica (NMO) attacks often are severe, are difficult to treat, and leave residual deficits. Here, we analyzed the frequency, sequence, and efficacy of therapies used for NMO attacks. METHODS: A retrospective review was made of patient records to assess demographic/diagnostic data, attack characteristics, therapies, and the short-term remission status (complete remission [CR], partial remission [PR], no remission [NR]). Inclusion criteria were NMO according to Wingerchuk's 2006 criteria or aquaporin-4 antibody-positive NMO spectrum disorder (NMOSD). Remission status was analyzed with generalized estimating equations (GEEs), a patient-based statistical approach. RESULTS: A total of 871 attacks in 185 patients (142 NMO/43 NMOSD, 82% female) were analyzed. The 1,153 treatment courses comprised high-dose intravenous steroids (HD-S; n = 810), plasma exchange (PE; n = 192), immunoadsorption (IA; n = 38), other (n = 80), and unknown (n = 33) therapies. The first treatment course led to CR in 19.1%, PR in 64.5%, and NR in 16.4% of attacks. Second, third, fourth, and fifth treatment courses were given in 28.2%, 7.1%, 1.4%, and 0.5% of attacks, respectively. This escalation of attack therapy significantly improved outcome (p < 0.001, Bowker test). Remission rates were higher for isolated optic neuritis versus isolated myelitis (p < 0.001), and for unilateral versus bilateral optic neuritis (p = 0.020). Isolated myelitis responded better to PE/IA than to HD-S as first treatment course (p = 0.037). Predictors of CR in multivariate GEE analysis were age (odds ratio [OR] = 0.97, p = 0.011), presence of myelitis (OR = 0.38, p = 0.002), CR from previous attack (OR = 6.85, p < 0.001), and first-line PE/IA versus HD-S (OR = 4.38, p = 0.006). INTERPRETATION: Particularly myelitis and bilateral optic neuritis have poor remission rates. Escalation of attack therapy improves outcome. PE/IA may increase recovery in isolated myelitis.
Subject(s)
Neuromyelitis Optica/therapy , Outcome Assessment, Health Care/statistics & numerical data , Registries/statistics & numerical data , Adult , Female , Germany , Humans , Male , Middle Aged , Neuromyelitis Optica/drug therapy , Remission Induction , Retrospective StudiesABSTRACT
OBJECTIVE: To analyse predictors for relapses and number of attacks under different immunotherapies in patients with neuromyelitis optica spectrum disorder (NMOSD). DESIGN: This is a retrospective cohort study conducted in neurology departments at 21 regional and university hospitals in Germany. Eligible participants were patients with aquaporin-4-antibody-positive or aquaporin-4-antibody-negative NMOSD. Main outcome measures were HRs from Cox proportional hazard regression models adjusted for centre effects, important prognostic factors and repeated treatment episodes. RESULTS: 265 treatment episodes with a mean duration of 442 days (total of 321 treatment years) in 144 patients (mean age at first attack: 40.9 years, 82.6% female, 86.1% aquaporin-4-antibody-positive) were analysed. 191 attacks occurred during any of the treatments (annual relapse rate=0.60). The most common treatments were rituximab (n=77, 111 patient-years), azathioprine (n=52, 68 patient-years), interferon-ß (n=32, 61 patient-years), mitoxantrone (n=34, 32.1 patient-years) and glatiramer acetate (n=17, 10 patient-years). Azathioprine (HR=0.4, 95% CI 0.3 to 0.7, p=0.001) and rituximab (HR=0.6, 95% CI 0.4 to 1.0, p=0.034) reduced the attack risk compared with interferon-ß, whereas mitoxantrone and glatiramer acetate did not. Patients who were aquaporin-4-antibody-positive had a higher risk of attacks (HR=2.5, 95% CI 1.3 to 5.1, p=0.009). Every decade of age was associated with a lower risk for attacks (HR=0.8, 95% CI 0.7 to 1.0, p=0.039). A previous attack under the same treatment tended to be predictive for further attacks (HR=1.5, 95% CI 1.0 to 2.4, p=0.065). CONCLUSIONS: Age, antibody status and possibly previous attacks predict further attacks in patients treated for NMOSD. Azathioprine and rituximab are superior to interferon-ß.
Subject(s)
Immunotherapy/methods , Neuromyelitis Optica/drug therapy , Adult , Aquaporin 4/immunology , Autoantibodies/blood , Azathioprine/therapeutic use , Cohort Studies , Female , Follow-Up Studies , Germany , Glatiramer Acetate/therapeutic use , Humans , Interferon-beta/therapeutic use , Long-Term Care , Male , Middle Aged , Mitoxantrone/therapeutic use , Neuromyelitis Optica/immunology , Prognosis , Recurrence , Registries , Retrospective Studies , Rituximab/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Gender and age at onset are important epidemiological factors influencing prevalence, clinical presentation, and treatment response in autoimmune diseases. OBJECTIVE: To evaluate the impact of female sex and fertile age on aquaporin-4-antibody (AQP4-ab) status, attack localization, and response to attack treatment in patients with neuromyelitis optica (NMO) and its spectrum disorders (neuromyelitis optica spectrum disorder (NMOSD)). METHODS: Female-to-male ratios, diagnosis at last visit (NMO vs NMOSD), attack localization, attack treatment, and outcome were compared according to sex and age at disease or attack onset. RESULTS: A total of 186 NMO/SD patients (82% female) were included. In AQP4-ab-positive patients, female predominance was most pronounced during fertile age (female-to-male ratio 23:1). Female patients were more likely to be positive for AQP4-abs (92% vs 55%; p < 0.001). Interval between onset and diagnosis of NMO/SD was longer in women than in men (mean 54 vs 27 months; p = 0.023). In women, attacks occurring ⩽40 years of age were more likely to show complete remission ( p = 0.003) and better response to high-dose intravenous steroids ( p = 0.005) compared to woman at >40 years. CONCLUSION: Our data suggest an influence of sex and age on susceptibility to AQP4-ab-positive NMO/SD. Genetic and hormonal factors might contribute to pathophysiology of NMO/SD.
Subject(s)
Neuromyelitis Optica/immunology , Adolescent , Adult , Age Distribution , Age of Onset , Aged , Aquaporin 4/immunology , Autoantibodies/immunology , Female , Fertility/immunology , Humans , Male , Middle Aged , Neuromyelitis Optica/genetics , Sex Characteristics , Young AdultABSTRACT
Treatment of neuropathic pain (NP) symptoms associated with multiple sclerosis (MS) is frequently insufficient. Yet, cannabis is still rarely offered for treatment of pain. This clinical trial aimed at showing the positive benefit-risk ratio of dronabinol. Two hundred forty MS patients with central NP entered a 16-weeks placebo-controlled phase-III study followed by a 32-weeks open-label period. One hundred patients continued therapy for overall up to 119 weeks. Primary endpoint was change of pain intensity on the 11-point Numerical Rating Scale over a 16-weeks treatment period. Safety was assessed on the basis of adverse reactions (ARs), signs of dependency and abuse. Pain intensity during 16-weeks dronabinol and placebo treatment was reduced by 1.92 and 1.81 points without significant difference in between (p = 0.676). Although the proportion of patients with ARs was higher under dronabinol compared to placebo (50.0 vs. 25.9%), it decreased during long-term use of dronabinol (26%). No signs of drug abuse and only one possible case of dependency occurred. The trial results demonstrate that dronabinol is a safe long-term treatment option.
Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Dronabinol/therapeutic use , Neuralgia/drug therapy , Adult , Double-Blind Method , Female , Humans , Male , Middle AgedABSTRACT
OBJECTIVE: Environmental conditions (eg, latitude) play a critical role in the susceptibility and severity of many autoimmune disorders, including multiple sclerosis (MS). Here, we investigated the mechanisms underlying the beneficial effects of immune regulatory processes induced in the skin by moderate ultraviolet B (UVB) radiation on central nervous system (CNS) autoimmunity. METHODS: Effects of UVB light were analyzed in a murine model of CNS autoimmunity (experimental autoimmune encephalomyelitis). Additionally, patients with relapsing-remitting MS were treated with narrowband UVB phototherapy. Immunomodulatory effects were examined in skin biopsies, serum samples, and immune cells of the peripheral blood. RESULTS: Regulatory T cells (Tregs), which are induced locally in the skin-draining lymph nodes in response to UVB exposure, connect the cutaneous immune response to CNS immunity by migration to the sites of inflammation (blood, spleen, CNS). Here, they attenuate the inflammatory response and ameliorate disease symptoms. Treg-inducing tolerogenic dendritic cells (DCs) were further necessary for induction of this systemic immune regulation by UVB radiation, because ablation of Langerhans cells abolished the UVB-induced phenotype. MS patients treated with UVB phototherapy showed an increase in induced Tregs and tolerogenic DCs accompanied by the downregulation of the T-cell effector cytokine interleukin 21. The treatment further induced elevated serum levels of vitamin D. INTERPRETATION: Local UVB radiation of the skin influences systemic immune reactions and attenuates systemic autoimmunity via the induction of skin-derived tolerogenic DCs and Tregs. Our data could have implications for the understanding or therapeutic modulation of environmental factors that influence immune tolerance.
Subject(s)
Encephalomyelitis, Autoimmune, Experimental/radiotherapy , Immunity, Cellular/radiation effects , Multiple Sclerosis, Relapsing-Remitting/radiotherapy , T-Lymphocytes, Regulatory/radiation effects , Ultraviolet Rays , Ultraviolet Therapy , Adult , Animals , Cells, Cultured , Dendritic Cells/immunology , Dendritic Cells/radiation effects , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/pathology , Female , Humans , Immunity, Cellular/immunology , Male , Mice , Mice, Congenic , Mice, Inbred C57BL , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/immunology , Multiple Sclerosis, Relapsing-Remitting/pathology , T-Lymphocytes, Regulatory/immunology , Ultraviolet Therapy/methods , Young AdultABSTRACT
BACKGROUND: The exact pathophysiology of cluster headache (CH) is still not fully clarified. Various studies confirmed changes in ocular blood flow during CH attacks. Furthermore, vasoconstricting medication influences blood supply to the eye. We investigated the retina of CH patients for structural retinal alterations with optical coherence tomography (OCT), and how these changes correlate to headache characteristics, oxygen use and impaired visual function. METHODS: Spectral domain OCT of 107 CH patients - 67 episodic, 35 chronic, five former chronic sufferers - were compared to OCT from 65 healthy individuals. Visual function tests with Sloan charts and a substantial ophthalmologic examination were engaged. RESULTS: Reduction of temporal and temporal-inferior retinal nerve fibre layer (RNFL) thickness was found in both eyes for CH patients with a predominant thinning on the headache side in the temporal-inferior area. Chronic CH patients revealed thinning of the macula compared to episodic suffers and healthy individuals. Bilateral thinning of temporal RNFL was also found in users of 100% oxygen compared to non-users and healthy controls. Visual function did not differ between patients and controls. DISCUSSION: Our OCT findings show a systemic effect causing temporal retinal thinning in both eyes of CH patients possibly due to attack-inherent or medication-induced frequent bilateral vessel diameter changes. The temporal retina with its thinly myelinated parvo-cellular axons and its more susceptible vessels for the vasoconstricting influence of oxygen inhalation seems to be predisposed for tissue damage-causing processes related to CH.
Subject(s)
Cluster Headache/pathology , Optic Nerve/pathology , Retina/pathology , Adult , Female , Humans , Male , Middle Aged , Tomography, Optical CoherenceABSTRACT
OBJECTIVES: Individual differences in underlying, "basal" pain sensitivity are large and have clinical implications. Some studies have suggested that basal pain sensitivity may also predict the outcome of pain treatment. Multidisciplinary chronic pain management programs are effective, but treatment success is individually very different. Therefore, identification of predictors of treatment success is important. This study investigated if basal pain sensitivity predicted the outcome of a 4-week outpatient multidisciplinary pain management program. DESIGN: Cohort study. SETTING: Chronic pain outpatient clinic at the Department of Anesthesiology, Intensive Care Medicine and Pain Therapy of the University of Münster. METHODS: Basal pain sensitivity was measured at treatment onset, using comprehensive experimental pain testing (thermal, pressure, and pinprick pain) and the pain sensitivity questionnaire. Primary (clinical pain intensity) and secondary (depression, anxiety, pain-related disability) outcome parameters were assessed at treatment start, at discharge and 6 months later. SUBJECTS: Sixty five adult chronic pain patients with mixed pain diagnoses. RESULTS: There were significant improvements in clinical pain intensity (from 6.1 ± 2.0 to 5.1 ± 1.8 [0-10]), depression and anxiety at discharge (all P < 0.001) and of clinical pain intensity (to 5.3 ± 2.3 [0-10]) and pain-related disability at 6 months (all P < 0.05). However, treatment outcome was not predicted by any of the basal pain sensitivity measures. DISCUSSION: Results show that basal pain sensitivity is not a reliable predictor of treatment outcome in mixed diagnosis multidisciplinary pain management programs, possibly due to the heterogeneity of patients enrolled in such programs. Clinically useful predictors of treatment success in this setting remain to be identified.
Subject(s)
Chronic Pain/physiopathology , Pain Clinics , Pain Measurement , Adolescent , Adult , Aged , Cohort Studies , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Outpatients , Predictive Value of Tests , Prognosis , Surveys and Questionnaires , Treatment Outcome , Young AdultABSTRACT
The objective of this study was to examine the subgroup of patients with chronic pruritus with dysesthetic subqualities for the presence of psychiatric comorbidities and to evaluate whether anxiety and depression make a difference in perception of somatosensory stimuli in quantitative sensory testing (QST). Forty-nine patients underwent routine diagnostics, a standardised QST testing battery, a psychosomatic evaluation for psychic comorbidities and filled out 2 questionnaires: the Patient Health Questionnaire for the assessment of depressive mood and the State Trait Anxiety Inventory. Twenty-seven (55.1%) of the sample had at least one psychiatric comorbid diagnosis. QST parameters were not correlated to anxiety and depression levels. We conclude that psychosomatic evaluation should become part of routine diagnostics of these patients in order to detect and treat psychiatric comorbidity. However, research on somatosensory aspects in these patients seems not to be affected by the levels of anxiety and depression.
Subject(s)
Anxiety/psychology , Depression/psychology , Paresthesia/psychology , Pruritus/diagnosis , Pruritus/physiopathology , Pruritus/psychology , Sensory Thresholds , Skin/innervation , Adult , Aged , Anxiety/diagnosis , Anxiety/physiopathology , Chronic Disease , Comorbidity , Cross-Sectional Studies , Depression/diagnosis , Depression/physiopathology , Female , Humans , Male , Middle Aged , Pain Perception , Pain Threshold , Paresthesia/diagnosis , Paresthesia/physiopathology , Pressure , Psychiatric Status Rating Scales , Psychometrics , Risk Factors , Surveys and Questionnaires , ThermosensingABSTRACT
BACKGROUND: A lack of habituation of different evoked potential modalities in migraine patients in-between attacks has been suggested. METHODS: This study investigates cortical response after painful stimuli evaluated by contact heat evoked potentials (CHEPs) and quantitative sensory testing (QST) during the migraine-free interval. We enrolled 22 migraine patients and 22 healthy subjects. RESULTS: Cortical potentials after contact heat stimulation of the cheeks and the volar forearm at a temperature of 51°C showed significantly reduced A-δ-amplitudes in patients and healthy controls. When the subjects' attention was drawn to an arithmetic task, a partial lack of habituation of amplitude could be seen in migraine patients. QST did not show any difference between migraineurs and controls. CONCLUSION: Our findings can be primarily deemed to demonstrate that patients and healthy controls show significantly lower amplitudes while performing the calculation task. Without performing the calculation task we could not show the expected lack of habituation in migraineurs. Yet, while performing the calculation task our results partly suggest that hypothesis.
Subject(s)
Evoked Potentials/physiology , Habituation, Psychophysiologic/physiology , Hot Temperature , Migraine Disorders/physiopathology , Pain/physiopathology , Adult , Female , Humans , Migraine Disorders/diagnosis , Pain/diagnosis , Young AdultABSTRACT
OBJECTIVE: To evaluate the efficacy of an evidence-based patient information programme aiming to increase informed choice in patients with early multiple sclerosis (MS). BACKGROUND: Patients with early MS face a number of uncertainties concerning diagnosis, prognosis and effectiveness of immunotherapy. Prior studies suggest that evidence-based patient information combined with group education can promote informed choice in MS patients. METHODS: A 12-month, six-centre, double-blind randomised controlled clinical trial with 192 patients with a diagnosis of confirmed relapsing-remitting MS or clinical isolated syndrome in Germany. A 4-h interactive evidence-based educational programme was compared with a 4-h MS-specific stress management programme. The primary endpoint was informed choice after 6 months comprising risk knowledge and congruency between attitude towards immunotherapy and actual immunotherapy uptake. Secondary endpoints included autonomy preference, decision autonomy, decisional conflict and satisfaction, anxiety and depression, and number of immunotherapies. RESULTS: For the primary endpoint, a significant difference was shown with 50 of 85 (59%) participants in the intervention group achieving informed choice after 6 months compared with 18 of 89 (20%) in the control group (OR 0.2 (95% CI 0.1 to 0.4), p<0.001). Four weeks after the intervention, more participants in the intervention group showed good risk knowledge (difference between groups 39% (95% CI 26% to 53%), p<0.001). There were no significant differences between groups for attitude towards immunotherapy and for immunotherapy uptake. There were trends towards increased autonomy preference after the intervention and increased adherence to immunotherapies in the intervention group. CONCLUSIONS: The intervention significantly increased informed choice and relevant risk knowledge without negative side effects.
Subject(s)
Evidence-Based Practice/methods , Health Knowledge, Attitudes, Practice , Multiple Sclerosis, Relapsing-Remitting , Patient Education as Topic , Adolescent , Adult , Decision Making , Double-Blind Method , Female , Humans , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Multiple Sclerosis, Relapsing-Remitting/psychologyABSTRACT
BACKGROUND: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. OBJECTIVE: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. METHODS: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). RESULTS: Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. CONCLUSION: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.
Subject(s)
Antibodies/blood , Aquaporin 4/immunology , Neuromyelitis Optica/blood , Neuromyelitis Optica/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Brain Stem/pathology , Cohort Studies , Disability Evaluation , Female , Humans , Magnetic Resonance Imaging , Male , Methylprednisolone/therapeutic use , Middle Aged , Neuromyelitis Optica/diagnosis , Neuromyelitis Optica/mortality , Oligoclonal Bands/cerebrospinal fluid , Recurrence , Retrospective Studies , Statistics as Topic , Treatment Outcome , Young AdultABSTRACT
Interferon-ß (IFN-ß) stabilizes the blood-brain barrier (BBB) in vitro. Here we investigated the effect of serum from 15 IFN-ß-1b-treated multiple sclerosis (MS) patients on the permeability read-outs of small solutes in an in vitro BBB model consisting of human brain microvascular endothelial cells in co-culture with rat astrocytes. The addition of sera from IFN-ß-treated patients resulted in a significantly (p < 0.05) reduced permeability as compared with untreated patients. Our findings show that sera from IFN-ß-1b-treated MS patients have a stabilizing effect on the in vitro BBB. We suggest an unknown potentially pro-inflammatory factor in the serum of MS patients that may lead to a BBB dysfunction and can be modulated by IFN-ß.
Subject(s)
Blood Proteins/pharmacology , Blood-Brain Barrier/metabolism , Endothelial Cells/metabolism , Interferon-beta/therapeutic use , Multiple Sclerosis/drug therapy , Adjuvants, Immunologic/therapeutic use , Adult , Animals , Astrocytes/cytology , Biomarkers/blood , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/immunology , Cell Line, Transformed , Coculture Techniques , Drug Monitoring/methods , Endothelial Cells/cytology , Endothelial Cells/immunology , Female , Humans , Interferon beta-1b , Male , Middle Aged , Multiple Sclerosis/immunology , Multiple Sclerosis/metabolism , RatsABSTRACT
Notalgia paraesthetica is a neuropathic pruritus on the back. The aim of this retrospective study was to examine patient characteristics in a consecutive cohort from Brazil and Germany. A total of 65 patients (49 women, 16 men; age range 25-80 years, mean 56.2 ± 12.7 years; median 57.0 years) were investigated in order to determine the spinal or peripheral origin of notalgia paraesthetica. Protein gene product 9.5-positive intraepidermal nerve fibers were significantly reduced in the pruritic compared with the non-lesional area (p < 0.05). In 32.3% of patients, radiological examinations showed a stenosis and in 47.7% a degeneration. A correlation between the radiological findings and the exact dermatomal localization of notalgia paraesthetica was found in 15.7% of the involved areas. The significant reduction in intraepidermal nerve fiber density suggests that damage to the peripheral nerves is a more important aetiological factor than spinal changes in notalgia paraesthetica.
Subject(s)
Peripheral Nerves/pathology , Peripheral Nervous System Diseases/pathology , Pruritus/pathology , Skin/innervation , Adult , Aged , Aged, 80 and over , Back , Biomarkers/analysis , Biopsy , Brazil/epidemiology , Female , Germany/epidemiology , Humans , Immunohistochemistry , Magnetic Resonance Imaging , Male , Middle Aged , Peripheral Nerves/chemistry , Peripheral Nervous System Diseases/epidemiology , Pruritus/diagnostic imaging , Pruritus/epidemiology , Retrospective Studies , Skin/pathology , Spinal Cord Compression/diagnostic imaging , Spinal Cord Compression/epidemiology , Spinal Cord Compression/pathology , Spinal Nerves/chemistry , Spinal Nerves/pathology , Tomography, X-Ray Computed , Ubiquitin Thiolesterase/analysisABSTRACT
Former studies suggest an additional involvement of the sensory nervous system, beside the involuntary contractions of antagonist muscles, in idiopathic hand dystonia. We studied contact heat-evoked potentials and quantitative sensory testing (QST) in 10 patients suffering from idiopathic hand dystonia and 10 age-matched healthy controls. Cortical potentials recorded from the vertex (Pz) after contact heat stimulation of the volar forearm and the dorsum of the hand at a temperature of 51°C showed significantly reduced A-δ-amplitudes. Numerical pain ratings on the affected side in comparison to the unaffected side and to healthy controls were significantly reduced. QST results showed an impairment of the thermal detection thresholds, the mechanical pain sensitivity and the mechanical pain threshold at the affected body side of the patients. Our results suggest a loss of distinct sensory functions of the affected hand in comparison with the contralateral hand and to matched healthy subjects in patients suffering from idiopathic hand dystonia. For the first time, an extended loss of sensory function could be shown in patients suffering from idiopathic hand dystonia.
Subject(s)
Dystonia/complications , Dystonia/pathology , Hand/physiopathology , Sensation Disorders/etiology , Adult , Aged , Case-Control Studies , Electroencephalography/methods , Evoked Potentials, Somatosensory/physiology , Female , Hand/innervation , Hot Temperature , Humans , Male , Middle Aged , Pain Measurement , Pain Threshold/physiology , Physical Stimulation/methods , Reaction Time/physiology , VibrationABSTRACT
BACKGROUND: Brachioradial pruritus (BRP) describes a rare form of itching occurring at the dorsolateral part of the forearms. Recent case reports suggest that BRP may be attributed to cervical lesions or spine neoplasms. OBJECTIVE: We sought to determine the incidence of cervical spine changes in BRP and to correlate the localization of spinal lesions with the dermatomal presence of pruritus. METHODS: Magnetic resonance tomography (MRT) of the cervical spinal cord, a chest x-ray, and a skin biopsy were performed in 41 patients (28 female, 13 male; 59.0 ± 10.6 years) with BRP. Patients completed an itch questionnaire (NeuroDerm Questionnaire) that included a dermatome chart and the Northwick Park Neck Pain Questionnaire. RESULTS: The patients marked the locations C5 (90.2%) and C6 (100%) on the dermatome chart. All patients had detectable MRT changes. In 80.5% of the patients, stenosis of the intervertebral foramen or protrusions of the cervical disk led to nerve compression. The location of the nerve compression lesions correlated significantly with the dermatomal localization of the pruritus (Spearman correlation coefficient 0.893; P < .01). No spinal neoplasm was observed, and 19.5% of the patients had degenerative changes without significant correlation to the dermatomal localization of pruritus. LIMITATION: No healthy control group without pruritus was investigated. CONCLUSION: BRP may result from cervical nerve compression, and rarely, it may also stem from degenerative changes. Our findings suggest that even slight cervical changes detected on MRT may alter itch afferents and lead to BRP. Spinal cord tumors are rare and should be ruled out by a cervical spine MRT.
Subject(s)
Cervical Vertebrae/pathology , Forearm , Pruritus/etiology , Spinal Diseases/complications , Adult , Aged , Cervical Vertebrae/diagnostic imaging , Female , Forearm/diagnostic imaging , Forearm/innervation , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nerve Compression Syndromes/complications , Pruritus/pathology , Tomography, X-Ray ComputedSubject(s)
General Practice , Stroke/diagnosis , Stroke/therapy , Diagnosis, Differential , Epilepsy/diagnosis , Epilepsy/therapy , Humans , Migraine with Aura/diagnosis , Migraine with Aura/therapy , Neurologic Examination , Risk Factors , Stroke/etiology , Thrombolytic Therapy , Treatment Outcome , Vertigo/diagnosis , Vertigo/therapyABSTRACT
The serotonergic system plays a major role in the etiology of migraine. The rate-limiting enzyme in serotonin homeostasis and availability is tryptophan hydroxylase (TPH). The TPH2 isoform is responsible for the cerebral serotonin biosynthesis. To investigate the role of genetic variation in TPH2 in the pathogenesis of migraine eight haplotype tagging SNPs covering the whole TPH2 gene where chosen using Haploview and genotyped in 503 migraineurs and 515 healthy controls. Association analysis was performed on a single SNP and haplotype basis using χ² and logistic regression analysis. Single SNP analysis revealed a weak association with migraine, which did not remain after correction for multiple testing. Haplotype analyses revealed association of a haplotype with migraine without aura. Stratification by aura and triptan response did not reveal a positive association with the investigated polymorphisms. These results suggest a possible influence of genetic variation in TPH2 in the pathogenesis of migraine.
Subject(s)
Genetic Predisposition to Disease/genetics , Migraine Disorders/genetics , Polymorphism, Single Nucleotide , Tryptophan Hydroxylase/genetics , Adult , Female , Genome-Wide Association Study , Genotype , Haplotypes , Humans , MaleABSTRACT
BACKGROUND: The syndrome of the sinking skin flap (SSSF) with delayed sensorimotor deficits after craniectomy is not well known and often neglected. Among various postulated causes, there is evidence that disturbed brain perfusion may be related to the observed symptoms, and that cranioplasty reliably alleviates these symptoms. We report a case of sinking skin flap syndrome (SSFS) with recovery from neurological sensorimotor deficits after cranioplasty correlated with pre- and postsurgical MR brain perfusion studies. CASE PRESENTATION: A 42-year-old woman presented with slowly progressive sensorimotor paresis of her left arm after decompressive extensive craniectomy due to subarachnoid hemorrhage four months ago. Her right cranium showed a "sinking skin flap". After cranioplastic repair of her skull defect, the patient fully recovered from her symptoms. Before cranioplasty, reduced brain perfusion in the right central cortical region was observed in MR-perfusion images. After cranioplasty, a marked increase in brain perfusion was observed which correlated with objective clinical recovery. CONCLUSION: There is increasing evidence that impaired blood flow is responsible for delayed motor deficits in patients with sinking skin flap syndrome in the area of compressed brain regions. Symptoms should be evaluated by brain perfusion imaging complementing surgical decision-making.
Subject(s)
Brain/blood supply , Craniotomy , Decompressive Craniectomy/adverse effects , Surgical Flaps/adverse effects , Adult , Cerebrovascular Circulation , Female , Hemodynamics , Humans , Magnetic Resonance Imaging , Paresis/etiology , Paresis/surgery , Paresthesia/etiology , Paresthesia/surgery , Perfusion Imaging , Subarachnoid Hemorrhage/surgeryABSTRACT
During anterior scoliosis instrumentation with a dual-rod system, the vertebrae are dissected anterolaterally. After surgery, some patients report a change in temperature perception and perspiration in the lower extremities. Sympathetic lesions might be an explanation for this. The aim of this clinical study was to investigate sympathetic function after anterior scoliosis instrumentation. A total of 24 female patients with idiopathic scoliosis (mean age at follow-up, 23.8 years) who had undergone anterior instrumentation on average 6.6 years earlier were included. Due to the suspected relevance of the sympathetic L2 ganglion, two groups were created: a T12 group, in which instrumentation down to T12 was carried out (n = 12), and an L3 group, in which instrumentation down to L3 was done (n = 12). Sympathetic function was assessed by measuring skin temperature at the back of the foot, a plantar ninhydrin sweat test and sympathetic skin responses (SSRs) following electrical stimulation. The side on which the surgical approach was carried out was compared with the contralateral, control side. Health-related quality of life was investigated using the Scoliosis Research Society SRS-22 patient questionnaire. In the T12 group, mean temperatures of 29.6 degrees C on the side of the approach versus 29.5 degrees C on the control side were measured (P > 0.05); in the L3 group, the mean temperatures were 33.2 degrees C on the approach side versus 30.5 degrees C on the control side (P = 0.001). A significant difference between the T12 group and the L3 group (P < 0.001) was observed on the approach side, but not on the control side (P = 0.15). The ninhydrin sweat test showed reduced perspiration in 11 of 12 patients in the L3 group on the approach side in comparison with the control side (P = 0.002). In the T12 group, no significant differences were noted between the left and right feet. SSRs differed significantly between the two groups (P = 0.005). They were detected in all nine analyzable patients in the T12 group on both sides. In the L3 group, they were found on the approach side only in 4 of 11 analyzable patients versus 11 patients on the control side. The results of the SRS-22 questionnaire did not show any significant differences between the two groups. In conclusion, anterior scoliosis instrumentation with a dual-rod system including vertebrae down to L3 regularly leads to lesions in the sympathetic trunk. These are detectable with an increase in temperature, reduced perspiration and reduced SSRs. The caudal level of instrumentation (T12 vs. L3) has an impact on the extent of impairment, supporting the suspected importance of the L2 ganglion. The clinical outcome does not seem to be significantly limited by sympathetic trunk lesions.