Aki Hietaharju

EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases

Despite high‐dose intravenous immunoglobulin (IVIG) is widely used in treatment of a number of immune‐mediated neurological diseases, the consensus on its optimal use is insufficient. To define the evidence‐based optimal use of IVIG in neurology, the recent papers of high relevance were reviewed and consensus recommendations are given according to EFNS guidance regulations. The efficacy of IVIG has been proven in Guillain‐Barré syndrome (level A), chronic inflammatory demyelinating polyradiculoneuropathy (level A), multifocal mononeuropathy (level A), acute exacerbations of myasthenia gravis (MG) and short‐term treatment of severe MG (level A recommendation), and some paraneoplastic neuropathies (level B). IVIG is recommended as a second‐line treatment in combination with prednisone in dermatomyositis (level B) and treatment option in polymyositis (level C). IVIG should be considered as a second or third‐line therapy in relapsing–remitting multiple sclerosis, if conventional immunomodulatory therapies are not tolerated (level B), and in relapses during pregnancy or post‐partum period (good clinical practice point). IVIG seems to have a favourable effect also in paraneoplastic neurological diseases (level A), stiff‐person syndrome (level A), some acute‐demyelinating diseases and childhood refractory epilepsy (good practice point).

Cerebral MRI abnormalities and their association with neuropsychiatric manifestations in SLE: a population‐based study

Objective: To evaluate the volumetric brain magnetic resonance imaging (MRI) findings in a population‐based sample of systemic lupus erythematosus (SLE) patients and to detect a possible relationship between cerebral MRI abnormalities and specific neuropsychiatric (NP) manifestations. Methods: The study population consisted of patients with SLE (n = 43) in Pirkanmaa Health Care District, Finland and of a sex‐ and age‐stratified reference group from the general population (n = 43). In addition to a clinical neurological investigation, all subjects received a detailed neuropsychological assessment and an MRI study. Volumetric measures of cerebral atrophy as well as T1‐ and T2‐weighted lesions were obtained. SLE activity was assessed by the European Consensus Lupus Activity Measure (ECLAM) index, and accumulated NP abnormalities were measured by the Systemic Lupus International Collaborating Clinics (SLICC) damage index. A cumulative lifetime dose of glucocorticoids was determined from the patientrecords. Results: Compared with controls, SLE patients had increased volumes of both T1‐ and T2‐weighted lesions (p = 0.019 and p<0.0001, respectively) and increased cerebral atrophy (p<0.001). All the measured MRI parameters were statistically significantly higher in NPSLE than in non‐NPSLE patients. In SLE patients, cerebral atrophy was associated with cognitive dysfunction, epileptic seizures, and cerebrovascular disease; T1‐weighted lesions were associated with epileptic seizures and T2‐weighted lesions with cognitive dysfunction. All MRI parameters correlated significantly with the SLICC index but not with the ECLAM index. A positive correlation was found between a cumulative dose of glucocorticoids and cerebral atrophy in SLE patients. Conclusion: MRI abnormalities, including brain atrophy and T1‐ and T2‐weighted lesions, are significantly more common in patients with SLE than in the general population and they are related to specific NP manifestations. Our findings also provide support for the organic aetiology of cognitive dysfunction in SLE.

Nervous system manifestations in Sjögren's syndrome

Central and peripheral manifestations of the nervous system were evaluated in 48 Sjögrens syndrome patients. Fifty‐six percent of the patients had neurological disturbances. The most common manifestations were entrapment neuropathies (19%) and polyneuropathy (15%). Electrophysiological tests gave further evidence of subclinical nervous system involvement in Sjögrens syndrome: electroencephalography (EEG) was abnormal in 48%, and visual evoked potentials (VEP) in 12% of patients tested. To find possible neuropsychiatric abnormalities, the Minnesota Multiphasic Personality Inventory was applied, and 33/43 patients were found to have psychiatric symptoms. The most frequent were depressive symptoms. In 44% of the patients there was additional evidence of extraglandular involvement or autoimmune disorders. No correlation could be found between the groups of patients with or without neurological disturbances in relation to simultaneous occurrence of associated disorders. It is suggested that nervous system involvement in Sjögrens syndrome reflects the pathogenetic consequences of Sjögrens syndrome alone, and not those of associated autoimmune diseases or extraglandular disorders.

Cognitive impairment in systemic lupus erythematosus and neuropsychiatric systemic lupus erythematosus: a population-based neuropsychological study.

We present a cross-sectional, population-based neuropsychological study of systemic lupus erythematosus (SLE) patients identified within Tampere University Hospital district, Finland with 440,000 inhabitants. Patients with definite SLE in the age range of 16-65 years (n =46) and matched controls (n =46) underwent neurological examination and comprehensive neuropsychological testing. On the basis of medical examination, the SLE patients were divided into neuropsychiatric (NP+; n =15) and nonneuropsychiatric (NP—; n =31) cases. The neuropsychological test results revealed more prevalent cognitive impairment in the NP+ patients, indicating that this subgroup mostly accounts for neuropsychological changes in SLE. Most characteristic changes in NP+ were observed in domains of memory, psychomotor speed, and complex attention. This suggests nonspecific CNS involvement, which is in line with neurological manifestations of the disease.

A quantitative method for the assessment of intraepidermal nerve fibers in small–fiber neuropathy

AbstractObjectives The purpose of this paper is to present an easy–to–use and reproducible morphometrical method of determining the density of intraepidermal nerve fibers (IENF) per epidermal area with the corresponding reference range of the IENF–counts.Methods Thirty patients and 22 controls were included in this study. The patients were divided into three groups: small–fiber (SFN), diabetic and demyelinating neuropathy. All subjects underwent punch skin biopsy. Specimens were fixed routinely in formalin and thereafter embedded in paraffin. Nerve fibers were revealed using immunoperoxidase staining with panaxonal antibody PGP 9.5. Using light microscopy, immunopositive nerves were counted morphometrically per epidermal area (NPEA) and, for comparison, per epidermal length (NPEL).Results Both the NPEA and NPEL estimates of SFN and diabetic neuropathy group differed significantly from those of control specimen (p < 0.001 and p < 0.001, Mann–Whitney test). Our method of counting, NPEA, shows a good correlation to NPEL (r = 0.945).Conclusions IENF–counting by a new morphometric modification is reproducible and diagnostically sensitive and can easily be adopted in any laboratory familiar with the basic immunohistochemical methodology. The method is less dependent on costly technical support systems and seems to be less time consuming when compared with conventional methods for IENF–counting.

Elevated cerebrospinal fluid adiponectin and adipsin levels in patients with multiple sclerosis: a Finnish co-twin study

Background and purpose:  The aim of this study was to investigate the levels of three adipocytokines: leptin, adiponectin and adipsin, in serum and cerebrospinal fluid (CSF) of twins discordant for multiple sclerosis (MS). Adipose tissue is an important component connecting immune system and several tissues and organs including CNS. Fat cells produce adipocytokines, which seem to have a role in various autoimmune disorders including MS.

Nervous system involvement in systemic lupus erythematosus, Sjögren syndrome and scleroderma

Introduction. The purpose of this study was to determine, whether there are any differences in the occurrence of nervous system involvement in different systemic rheumatic diseases. The further aim of the present study was to identify and distinguish primary involvement of the nervous system by these diseases and involvement that may be secondary to confounding factors.

Case report A reversible neuronal antibody (anti‐Tr) associated paraneoplastic cerebellar degeneration in Hodgkin's disease

Paraneoplastic cerebellar degeneration (PCD) has been associated with a variety of neoplasms, most commonly with gynecologic tumors, breast cancer, small cell lung cancer, and Hodgkins disease (HD). In some patients PCD is associated with circulating antineuronal antibodies like anti‐Hu, anti‐Yo or anti‐Ri. Previously, only 5 patients with a new antineuronal antibody called anti‐Tr, proposed to be specific for HD, have been reported. We describe 1 further patient with HD and reversible PCD with a decline in anti‐Tr antibody titers in cerebrospinal fluid and serum corresponding to the improvement of clinical symptoms. At the present time the immunoreactive pattern observed in rat cerebellum is the only way to identify anti‐Tr antibodies and differentiate them from other antibodies that immunoreact with the Purkinje cells.

Neuropathic Pain and Psychological Morbidity in Patients with Treated Leprosy: A Cross-Sectional Prevalence Study in Mumbai

Background Neuropathic pain has been little studied in leprosy. We assessed the prevalence and clinical characteristics of neuropathic pain and the validity of the Douleur Neuropathique 4 questionnaire as a screening tool for neuropathic pain in patients with treated leprosy. The association of neuropathic pain with psychological morbidity was also evaluated. Methodology/Principal Findings Adult patients who had completed multi-drug therapy for leprosy were recruited from several Bombay Leprosy Project clinics. Clinical neurological examination, assessment of leprosy affected skin and nerves and pain evaluation were performed for all patients. Patients completed the Douleur Neuropathique 4 and the 12-item General Health Questionnaire to identify neuropathic pain and psychological morbidity. Conclusions/Significance One hundred and one patients were recruited, and 22 (21.8%) had neuropathic pain. The main sensory symptoms were numbness (86.4%), tingling (68.2%), hypoesthesia to touch (81.2%) and pinprick (72.7%). Neuropathic pain was associated with nerve enlargement and tenderness, painful skin lesions and with psychological morbidity. The Douleur Neuropathique 4 had a sensitivity of 100% and specificity of 92% in diagnosing neuropathic pain. The Douleur Neuropathique 4 is a simple tool for the screening of neuropathic pain in leprosy patients. Psychological morbidity was detected in 15% of the patients and 41% of the patients with neuropathic pain had psychological morbidity.

Investigation of neuropathic pain in treated leprosy patients in Ethiopia: a cross-sectional study

Summary Different types of pain occur in leprosy, and different mechanisms may underlie each type. Neuropathic pain is common among recently treated leprosy patients in Ethiopia. Abstract Pain can be a significant problem for treated leprosy patients. It can be nociceptive due to tissue inflammation occurring during episodes of immune mediated reactions, or neuropathic due to leprosy affecting the somatosensory system. There are sparse epidemiological data on the prevalence and impact of neuropathic pain in treated leprosy patients. Tools for assessing neuropathic pain have not been validated in leprosy. We have examined nature of pain in a cross‐sectional study to determine the prevalence of neuropathic pain (NP) in 80 recently treated leprosy patients in Ethiopia. Pain and depression were evaluated using the General Health Questionnaire (GHQ‐12) and the Brief Pain Inventory (BPI) questionnaire. The Douleur Neuropathique en 4 Questions (DN4) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) were used as screening tools for NP. Pain of any type was experienced by 60% of the patients. Pure nociceptive pain was experienced by 43%, pure NP by 11%, and mixed pain by 6%. Of the 14 patients who had NP either alone or in combination with nociceptive pain, 12 had high GHQ‐12 scores, indicating possible depression. The DN4 had sensitivity and specificity of 100% and 45%, whereas the LANSS had 85% and 42%, respectively. This is the first study to differentiate nociceptive from NP in leprosy patients. The prevalence of NP is high in recently treated Ethiopian leprosy patients. We have validated the use of DN4 in leprosy and it is easier to use than LANSS. Depression is a common co‐morbidity in patients with NP. The high prevalence and morbidity of NP in treated leprosy patients warrant clinical trials to assess the efficacy of pain therapies for leprosy‐associated NP.