Expecting the unexpected - a look into the future of diagnostics and therapy

As the leading association in the field of neurology, the EAN is always striving to do pioneering work by developing new approaches for the meeting and exchange of scientific knowledge. The theme of the anniversary year was “Happiness”. Positive news and inspiring experts pointed the way to the future of neurology.

Middle-aged and older adults who have frequent disturbing dreams may be more at risk of cognitive decline and dementia. Researchers from Imperial College London (United Kingdom) investigated the association between the frequency of self-reported distressing dreams and the risk of cognitive decline and dementia in men and women in the general population [1]. The team assessed the frequency of distressing dreams using data collected in middle-aged adults from the Midlife in the United States (MIDUS) study and in 2600 older adults from the Osteoporotic Fractures in Men Study (MrOS) and the Study of Osteoporotic Fractures (SOF). Compared to middle-aged adults who reported having no disturbing dreams at baseline, those who reported having weekly disturbing dreams had a fourfold risk of experiencing cognitive decline. In older adults, the difference in dementia risk was 2.2 times higher.

While stress, anxiety or depression can cause disturbing dreams, other factors such as scary content in movies or a person’s genes can also trigger disturbing dreams. Recent research has shown that some people have a set of genes that make them prone to nightmares. Other studies show that people whose parents have nightmares are more likely to have them. The link between nightmares and brain diseases such as Parkinson’s disease has already been established in the literature, but could also help predict autoimmune diseases such as lupus and attention deficit hyperactivity disorder (ADHD) in childhood. These correlations should therefore be investigated in detail. If the cause is psychological, appropriate treatment should be sought to better manage the stress levels, either through lifestyle changes, psychotherapy or medication. In the case of nightmares that have no obvious cause and impair quality of life, image therapy shortly before bedtime can be helpful.

Parental smoking increases the risk of MS

A study shows that selective exposure to parental smoking at a young age can increase the risk of MS in the general population in different ways [2]. Using data collected as part of the Environmental Risk Factors In Multiple Sclerosis (EnvIMS) study, a large multinational population-based case-control study, researchers examined the association between MS and smoking habits, maternal smoking during pregnancy and maternal or paternal smoking in the Canadian, Italian and Norwegian populations. In Norwegians, an association was found between MS and maternal smoking during pregnancy and maternal smoking. In Canadians, a tendency towards an association between paternal smoking and MS was found, while in the Italian population no significant association with parental smoking was found.

Selective exposure to parental smoking at a young age may increase the risk of MS in the general population and regardless of the subjects’ past or current smoking habits. However, the lack of an association between MS and parental smoking history in some populations may be due to the smaller effect on MS risk compared to other factors. There are a variety of genetic and environmental risk factors that interact in MS. The timing of exposure to environmental factors, e.g. breastfeeding or infections such as mononucleosis, is also important. In the early years of life, infection can be protective, but later in life it can be a risk factor.

While active smoking is a known risk factor for the development of MS and a poor prognosis, the effect of previous exposure to parental smoking, including maternal smoking during pregnancy, had not yet been well defined. When you compare two studies recently published on maternal smoking during pregnancy, they say the opposite. One says there is no link, while the other concludes that children of mothers who smoked had a higher risk of developing MS. This is confusing. Research needs to distinguish between maternal smoking in the prenatal period and parental smoking, i.e. passive smoking in childhood. Another factor that needs to be taken into account is that if your parents smoke, you are more likely to become a smoker, which in turn affects your risk of developing MS. So there are a lot of confounding factors in this type of study if you don’t adjust the results. Future research should further investigate not only MS risk factors but also patient prognosis.

Individual therapy management of myasthenia gravis

Myasthenia gravis (MG) is diagnosed by history and examination, autoantibody tests and electrophysiological tests [3]. MG is caused by autoantibodies that bind to the postsynaptic membrane at the neuromuscular junction. IgG antibodies against acetylcholine receptor (AChR), MuSK or LRP4 affect AChRs through receptor cross-linking, complement activation, AChR blockade or impaired AChR clustering. The IgG subclass varies. Both thymic hyperplasia and thymoma can induce the production of AChR autoantibodies and MG. In MG, active synthesis of new AChRs occurs and the structural postsynaptic changes are reversible. MG treatment should be in accordance with international guidelines and at the same time adapted to the individual patient. Treatment decisions should be made jointly by the neurologist and the patient. Treatment should be based on the autoantibody status, generalization and severity of MG and thymic pathology. Symptomatic drug therapy with acetylcholine esterase inhibitors is a primary therapy. Immunotherapy should be offered to all patients who have not achieved their treatment goals. The combination of prednisolone and azathioprine is the first choice for immunotherapy. Rituximab is an alternative, especially for MuSK-MG and new-onset AChR-MG. Mycophenolate, tacrolimus and methotrexate are other commonly used immunosuppressants. Thymectomy should be performed for thymoma and generalized MG with AChR antibodies if the patient is under 50 years of age. Complement inhibitors and FcRn blockers have a proven and clinically useful effect in most MG patients. They improve symptoms after just one to two weeks. Due to the very high drug costs, their use is limited to difficult-to-treat and severe MG and depends on local availability, formal approval and reimbursement policies. In refractory cases, new and experimental therapies may be considered. Physical activity is safe and beneficial in MG. At least 150 minutes per week is recommended. Successful MG treatment depends on the timely combination of measures.

Real-world data at nOH

The treatment of neurogenic orthostatic hypotension (nOH) is based on consensus-based approaches. There is a lack of real-world data on long-term efficacy and safety. Now the response to antihypotonics has been investigated in a longitudinal cohort of patients with synuclein-induced nOH (PAF, PD, DLB and MSA) [4]. The severity of cardiovascular autonomic insufficiency was determined by autonomic function tests. Response to medication was measured with a semi-composite questionnaire that assessed the number of falls/month and hospitalizations/trimester, orthostatic symptom burden, quality of life and blood pressure monitoring. 101 patients completed the questionnaire. 61 patients were in long-term treatment (26 with one, 35 with several antihypertensive drugs), 40 in non-pharmacological treatment due to early disease stage, severe supine hypertension, immobilization or insensitivity to medication. The number of falls and hospitalizations was 2 and 0.3, respectively. The composite OHQ score (range 1-10) was 7.24. The composite SF36 scores for physical and mental complaints (range: 0-100) were 33.2 and 38.9, respectively. The level of nOH was 56/27 mmHg in treated patients compared to 29/6 mmHg in untreated patients. Despite multiple antihypertensive use, two-thirds of patients with nOH were significantly symptomatic, as confirmed by fall rates and hospitalizations. These results emphasize the critical nature of nOH, the current gaps in pharmacological treatment and the profound impact on patients’ daily functioning.

Subtypes in Parkinson’s disease

In Parkinson’s disease (PD), sleep is often impaired, with pain being one of the possible causes. This can lead to difficulties in initiating and maintaining sleep, one of the consequences being sleep fragmentation. Therefore, the relationship between pain and sleep disturbance in patients with Parkinson’s disease was investigated in more detail [5]. 131 Parkinson’s patients were included in this case-control study. The pain domains (according to the King’s Parkinson’s Disease Pain Scale, K PPS) were analyzed according to the presence of sleep disturbances. Based on a Pittsburgh Sleep Quality Index (PSQI) of >5, PD patients were categorized as “poor sleepers”, while patients with a score ≤5 were considered “good sleepers”. 25.19% of patients fell into the “good sleeper” category and 74.8% into the “poor sleeper” category. Patients in the “poor sleeper” category had more severe pain in all areas of the KPPS scale than patients in the “good sleeper” category, with statistically significant results for the following areas: Musculoskeletal pain, chronic pain, chronic pain or central pain, nocturnal pain or pain associated with akinesia, and radicular pain. The majority of the patients examined had a reduced quality of sleep. Their pain is more prominent than that of people with uninterrupted sleep. A focus on treatment

Survival with amyotrophic lateral sclerosis

The role of upper motor neuron (UMN) and lower motor neuron (LMN) involvement in amyotrophic lateral sclerosis (ALS) has been extensively studied in relation to clinical phenotype and survival. Conversely, it is not known whether the rate of change in UMN (ΔUMN) and LMN (ΔLMN) signs provides useful information about the evolution of ALS. A retrospective inpatient cohort of 1000 ALS patients has now been analyzed in this regard [5]. The burden of UMN and LMN signs was assessed using the Penn Upper Motor Neuron Score and Lower Motor Neuron Score, respectively. The time interval between symptom onset and first assessment was used to quantify ΔUMN and ΔLMN values. Survival, time from symptom onset to percutaneous endoscopic gastrostomy (PEG) and to non-invasive ventilation (NIV), were used as outcome measures. The ENCALS survival model was calculated for a subgroup of patients.

The ΔUMN and ΔLMN values were found to be negatively associated with survival (ΔUMN: HR = 1.30; ΔLMN: HR = 4.22), time to PEG (ΔUMN: HR = 1.34; ΔLMN: HR = 4.46) and time to NIV (ΔUMN: HR = 1.23; ΔLMN: HR = 5.0). A cut-off value of 0.195 for ΔLMN was determined to predict patients with expected short or longer survival. ENCALS groups characterized by shorter survival were significantly associated with higher ΔUMN and ΔLMN values compared to those with longer survival.

The results suggest that ΔUMN and ΔLMN may represent reliable clinical indices for estimating disease progression and survival of ALS patients. Indeed, these two measures provide distinct clinical information in addition to the information derived from the total burden of UMN and LMN signs at initial assessment.

Congress:10^th Congress of the European Academy of Neurology (EAN)

Literature:

Otaiku A, et al: Distressing dreams, cognitive decline, and risk of dementia: A prospective study of three population-based cohorts. 10^th Annual Congress of the European Academy of Neurology, 29.06.-02.07.2024, Helsinki.
Ferri C, et al: Parental smoking exposure and risk for multiple sclerosis among adults: the EnvIMS study. 10^th Annual Congress of the European Academy of Neurology, 29.06.-02.07.2024, Helsinki.
Gilhus NE, et al: Myasthenia gravis; Individualized treatment based on a well-defined disease pathogenesis. 10^th Annual Congress of the European Academy of Neurology, 29.06.-02.07.2024, Helsinki.
Sajeev S, et al: Long-term efficacy of antihypotensive drugs for neurogenic OH: Real-world data in patients with alpha-synucleinopathies. 10^th Annual Congress of the European Academy of Neurology, 29.06.-02.07.2024, Helsinki.
Murasan I, et al: Pain subtypes and sleep dysfunction in Parkinson’s disease. 10^th Annual Congress of the European Academy of Neurology, 29.06.-02.07.2024, Helsinki.
6 Marazano A, et al: Rate of change in upper and lower motor neuron burden is associated with survival and in amyotrophic lateral sclerosis. 10^th Annual Congress of the European Academy of Neurology, 29.06.-02.07.2024, Helsinki.