[What is new in symptomatic MS treatment: Part 3-bladder dysfunction]. / Neues zur symptomatischen MS-Therapie: Teil 3 ­ Blasenfunktionsstörungen.

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKNMS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the symptoms of bladder dysfunction will be discussed.

[New aspects of symptomatic MS treatment: Part 4-sexual dysfunction and eye movement disorders]. / Neues zur symptomatischen MS-Therapie: Teil 4 ­ Störungen der Sexualfunktion und der Augenbewegungen.

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis (Klinisches Kompetenznetz Multiple Sklerose, KKNMS) in 2014, several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms as well as treatment goals are introduced in several individual contributions. In this article the symptoms of sexual dysfunction and eye movement disorders are discussed.

[New aspects of symptomatic MS treatment: Part 6 - cognitive dysfunction and rehabilitation]. / Neues zur symptomatischen MS-Therapie: Teil 6 ­ kognitive Störungen und Rehabilitation.

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis ("Klinisches Kompetenznetz Multiple Sklerose", KKN-MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in several individual contributions. In this article the symptoms of cognitive disorders and the growing impact of rehabilitation are discussed.

[New aspects of symptomatic MS treatment: Part 5 - fatigue]. / Neues zur symptomatischen MS-Therapie: Teil 5 ­ Fatigue.

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis (Klinisches Kompetenznetz Multiple Sklerose, KKN-MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms as well as treatment goals are introduced in a series of 6 individual contributions. In this article the symptom of fatigue is discussed.

[What is new in symptomatic MS treatment: Part 2-gait disorder and spasticity]. / Neues zur symptomatischen MS­Therapie: Teil 2 ­ Gangstörung und Spastik.

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKN­MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the symptoms of gait disorders and spasticity will be discussed.

[What is new in symptomatic MS treatment: Part 1-introduction and methodical approach, ataxia and tremor]. / Neues zur symptomatischen MS­Therapie: Teil 1 ­ Einleitung und methodisches Vorgehen, Ataxie und Tremor.

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKN­MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the topic will be introduced, the methodical approach will be explained, and the treatment of ataxia and tremor will be discussed.

Spasticity in patients with multiple sclerosis--clinical characteristics, treatment and quality of life.

AIMS: To gain real-life data on demographic and clinical characteristics, treatment patterns, treatment satisfaction and quality-of-life of multiple sclerosis-related spasticity (MSS) in Germany. MATERIAL AND METHODS: MObility ImproVEment (MOVE 1), a cross-sectional burden-of-disease study, combines retrospective 12-month chart documentation with questionnaires for both, patients and physicians. Data were collected at office-based neurologists, MS outpatient clinics and rehabilitation centres in Germany. Structured documentation forms, questionnaires and validated instruments were used for data collection. Patients with mild to severe MSS were included. Participants documented the clinical characteristics, impact of MSS on daily living, quality-of-life, treatment patterns and satisfaction with available drug treatment stratified by severity of MSS. Severity was assessed by patients and physicians. RESULTS: Of 419 patients enrolled at 42 centres from 4/2011 to 9/2011, 414 were available for analysis (mean age: 48.5 years; female: 64%). Most disturbing symptoms associated with spasticity reported by physicians and patients were stiffness (74%) and mobility restrictions (66%). Mean EQ-5D score fell from 0.6 to 0.3 with increasing severity of spasticity, while percentage of subjects with spasticity-related impairment of activities every day rose from 10% in patients with mild to 85% in patients with severe spasticity. At time of enrolment, 55% of patients received pharmacotherapy and 78% physiotherapy. These percentages increased with increasing severity (drugs: 39-84%; physiotherapy: 65-86%). Overall, 41% of physicians and 36% of patients were partial dissatisfied or dissatisfied with the effectiveness of available anti-spastic pharmacotherapy. CONCLUSIONS: Spasticity and its symptoms impair personal well-being and quality-of-life. Treatment of spasticity with drugs and physiotherapy is common, but satisfaction with the currently available anti-spastic pharmacotherapy is low.

[Importance and treatment of spasticity in multiple sclerosis : results of the MOVE 1 study]. / Bedeutung und Behandlung der Spastik bei Multipler Sklerose : Ergebnisse der MOVE-1-Studie.

BACKGROUND: The impact of spasticity induced by multiple sclerosis (MS) on patients and the applied treatment options have so far been insufficiently studied. METHODS: This was a multicentre, retrospective, nationwide study of the care situation of MS spasticity in Germany from the perspective of both patients and physicians. RESULTS: In this study 414 patients (mean age 48.6 years, 64.3 % women) from 42 centres were analyzed: 27 % suffered from mild, 44 % from moderate and 29 % from severe spasticity. The most common comorbidities were depression and anxiety (25.6 %) and 94.9 % suffered from concomitant symptoms (e.g. fatigue and bladder disorders). The severity of spasticity and its consequences were assessed by both patients and physicians and 54.8 % of physicians were dissatisfied with available treatment options. The most frequently cited disadvantages of currently available antispastic treatment were adverse effects (95.2 %) und insufficient effectiveness (88.1 %) and one third of patients sought help by self-medication. CONCLUSIONS: This initial assessment of MS-induced spasticity in Germany showed that patients experienced severe impairment due to spasticity. Available treatment options were assessed as dissatisfying.

Evaluation of Study and Patient Characteristics of Clinical Studies in Primary Progressive Multiple Sclerosis: A Systematic Review.

BACKGROUND: So far, clinical studies in primary progressive MS (PPMS) have failed to meet their primary efficacy endpoints. To some extent this might be attributable to the choice of assessments or to the selection of the study population. OBJECTIVE: The aim of this study was to identify outcome influencing factors by analyzing the design and methods of previous randomized studies in PPMS patients without restriction to intervention or comparator. METHODS: A systematic literature search was conducted in MEDLINE, EMBASE, BIOSIS and the COCHRANE Central Register of Controlled Trials (inception to February 2015). Keywords included PPMS, primary progressive multiple sclerosis and chronic progressive multiple sclerosis. Randomized, controlled trials of at least one year's duration were selected if they included only patients with PPMS or if they reported sufficient PPMS subgroup data. No restrictions with respect to intervention or comparator were applied. Study quality was assessed by a biometrics expert. Relevant baseline characteristics and outcomes were extracted and compared. RESULTS: Of 52 PPMS studies identified, four were selected. Inclusion criteria were notably different among studies with respect to both the definition of PPMS and the requirements for the presence of disability progression at enrolment. Differences between the study populations included the baseline lesion load, pretreatment status and disease duration. The rate of disease progression may also be an important factor, as all but one of the studies included a large proportion of patients with a low progression rate. In addition, the endpoints specified could not detect progression adequately. CONCLUSION: Optimal PPMS study methods involve appropriate patient selection, especially regarding the PPMS phenotype and progression rate. Functional composite endpoints might be more sensitive than single endpoints in capturing progression.

Coping with myasthenia gravis and implications for psychotherapy.

The aim of this study was to investigate psychosocial influences and mechanisms of coping to establish indications for psychotherapy in patients with myasthenia gravis. We investigated clinical symptoms, personality, psychopathology, and coping in 44 patients with myasthenia gravis. The patients' personalities were not characteristically altered, and in 29.5% (13/44) of them, preexistent, long-term psychiatric disturbances (according to International Classification of Diseases criteria) were present, which corresponds to the prevalence in the average population. In general, coping was characterized by an attitude of calmness and acceptance, which is attributable to effective medical treatment and could be considered an unspecific mode of coping with chronic diseases of moderate severity. Four women had undergone psychotherapy because of neurotic symptoms that were unrelated to myasthenia gravis. At the end of psychotherapy, their myasthenic symptoms had greatly improved or disappeared. Psychotherapeutic techniques may be helpful in patients with neurotic or reactive psychiatric symptoms, but there is no general implication for psychotherapy in myasthenic patients, especially if there is adequate "somatic" therapy.

Familial myopathy with elevated serum angiotensin-converting enzyme, creatine kinase and lactate dehydrogenase isoenzyme 5.

A family is reported in which two members presented with proximal myopathy associated with high serum levels of angiotensin-converting enzyme (SACE), creatine kinase (CK), and lactate dehydrogenase isoenzyme 5. Examination of three relatives revealed elevated SACE levels in all of them, but no myopathy. No evidence of sarcoidosis, the most common disease associated with high SACE levels, could be found. Muscle biopsies of the two affected men revealed myopathic features without granuloma formation. Extensive biochemical, metabolic, immunological, and microbiological studies were all non-contributory. Corticosteroid and, in one patient, azathioprine treatment resulted in an improvement of muscle weakness and in a decrease of SACE as well as CK levels.

Determination of erythrocyte-bound acetylcholinesterase activity for monitoring pyridostigmine therapy in myasthenia gravis.

Monitoring of pyridostigmine therapy in patients with myasthenia gravis is not routinely performed, since the daily pyridostigmine doses are adjusted to the patient's actual clinical status rather than to pyridostigmine plasma concentrations (PPC). Moreover, PPC determination is time-consuming and needs much technical equipment. Since pyridostigmine reversible blocks acetylcholinesterase (AChE) at the neuromuscular junction, we studied the correlation between the enzyme's blood activity (erythrocyte-bound AChE) and PPC, on the one hand, and between blood AChE activity and the clinical status of the individual patient, on the other. In five previously untreated patients with myasthenia gravis blood AChE activity decreased in accordance with the actual PPC after a single oral dose of 60 mg pyridostigmine (group A). Amelioration of the clinical status corresponded to the decrease of AChE activity in the same way. In another five patients, who were on stable pyridostigmine medication for at least 1 week, AChE activity and PPC were constant during the day (group B). Since it is easier to perform than PPC, our results suggest that the determination of AChE activity may be superior to measuring PPC for monitoring cholinesterase inhibitor therapy in selected cases.

99mTc-hexamethylpropylene amine oxime SPECT and X-ray CT in acute cerebral ischaemia.

Early diagnosis of acute cerebral ischaemia is still unsatisfactory, because X-ray computed tomography (CT) does not reveal the site and extent of hypoperfusion within the first 24 h. Single photon emission computed tomography (SPECT) using 99mTc-hexamethylpropylene amine oxime (HMPAO) may offer earlier information, since the distribution of HMPAO follows the actual cerebral perfusion pattern. We therefore investigated 53 patients suffering from acute cerebral ischaemia (10 with transient ischaemic attacks, 9 with prolonged ischaemic reversible neurological deficits, 34 with completed stroke). SPECT and CT examinations were performed on days 1, 3, and 14. On day 1, SPECT revealed hypoperfused areas in 42 patients, whereas CT showed hypodensities only in 5. The sensitivity of SPECT was higher in cortical compared with subcortical ischaemia. In patients suffering from reversible neurological deficits SPECT normalized in the follow-up, corresponding to clinical improvement. In completed stroke, SPECT demonstrated variable perfusion patterns with hypo-, normo-, and hypoperfused areas on day 3 and especially on day 14. In contrast to CT, HMPAO SPECT leads to early diagnosis of cerebral ischaemia, in particular within the cerebral cortex.

Progressive inflammatory lesions of the brain parenchyma in localized scleroderma of the head.

A patient with localized scleroderma of the head, uveitis, and Raynaud's phenomenon presented with generalized seizures, spastic hemiparesis, and local IgG production in the cerebrospinal fluid. Magnetic resonance imaging revealed progressive cortical and subcortical brain parenchymal lesions mainly adjacent to the cutaneous and bony lesions and probably of inflammatory origin.

The development of an epileptogenic focus. A case study with 99mTc-HMPAO SPECT.

A patient is described who developed complex partial seizures with secondary generalization 3 years after a severe viral encephalitis with a CT and EEG identified lesion in the left insular cortex and its surrounding structures. When the seizures first occurred CT and MRI as well as repeated interictal conventional EEG recordings were entirely normal. Single photon emission computed tomography (SPECT), however, revealed an area of increased 99mTc-hexamethyl propyleneamine oxime (HMPAO) uptake in the left insular cortex. After anticonvulsive therapy the seizures and the SPECT findings disappeared. 99mTc-HMPAO SPECT is a highly sensitive method for the demonstration of functional alterations in brain tissue. It can improve diagnosis of epilepsy and may provide additional information to monitor anticonvulsive therapy.

What is new in symptom management?

Many people with MS suffer from severe and disabling symptoms that restrict their social and private lives, and hence affect their quality of life; it is, therefore, essential that any symptoms that they experience are reduced effectively. Symptomatic treatment should also aim to prevent secondary complications that may result from existing disabilities. Since many MS patients are unaware that some of their complaints may be attributable to MS, e.g. fatigue, sexual dysfunction, pain or dysphagia, all patients should be thoroughly questioned about all healthcare issues and the results must be documented. In recent months, several studies about the treatment of important MS symptoms--like spasticity, pain, fatigue, bladder and sexual dysfunction, depression and cognitive impairment--have been published; this article will briefly summarize and discuss some of these treatments.