Caffeine for Headaches: Helpful or Harmful? A Brief Review of the Literature.

Consumption of caffeine in the diet, both daily and occasional, has a significant biological effect on the nervous system. Caffeine, through various and not yet fully investigated mechanisms, affects headaches. This is especially noticeable in migraine. In other headaches such as hypnic headache, post-dural puncture headache and spontaneous intracranial hypotension, caffeine is an important therapeutic agent. In turn, abrupt discontinuation of chronically used caffeine can cause caffeine-withdrawal headache. Caffeine can both relieve and trigger headaches.

The Pathogenetic Role of Melatonin in Migraine and Its Theoretic Implications for Pharmacotherapy: A Brief Overview of the Research.

Migraine is a chronic disease of global concern, regardless of socio-economic and cultural background. It most often and intensely affects young adults, especially women. Numerous mechanisms of a migraine attack have been identified (disturbances in the reaction of vessels, functions of neurotransmitters, cortical neurons, ion channels, receptors, the process of neurogenic inflammation), and many of its symptoms can be explained by activation of the hypothalamus and disturbances in its communication with other brain regions (including the brainstem). Numerous neuropeptides and neurochemical systems also play a role in migraine. One of them is melatonin, a hormone that allows the body to adapt to cyclically changing environmental and food conditions. In this article, we present the pathophysiological basis of melatonin release from the pineal gland and other tissues (including the intestines) under the influence of various stimuli (including light and food), and its role in stimulating the brain structures responsible for triggering a migraine attack. We analyze publications concerning research on the role of melatonin in various headaches, in various stages of migraine, and in various phases of the menstrual cycle in women with migraine, and its impact on the occurrence and severity of migraine attacks. Melatonin as an internally secreted substance, but also present naturally in many foods. It is possible to supplement melatonin in the form of pharmaceutical preparations, and it seems, to be a good complementary therapy (due to the lack of significant side effects and pharmacological interactions) in the treatment of migraine, especially: in women of childbearing age, in people taking multiple medications for other diseases, as well as those sensitive to pharmacotherapy.

Magnesium as an Important Factor in the Pathogenesis and Treatment of Migraine-From Theory to Practice.

So far, no coherent and convincing theory has been developed to fully explain the pathogenesis of migraine, although many researchers and experts emphasize its association with spreading cortical depression, oxidative stress, vascular changes, nervous excitement, neurotransmitter release, and electrolyte disturbances. The contribution of magnesium deficiency to the induction of cortical depression or abnormal glutamatergic neurotransmission is a likely mechanism of the magnesium-migraine relationship. Hence, there is interest in various methods of assessing magnesium ion deficiency and attempts to study the relationship of its intra- and extracellular levels with the induction of migraine attacks. At the same time, many clinicians believe that magnesium supplementation in the right dose and form can be a treatment to prevent migraine attacks, especially in those patients who have identified contraindications to standard medications or their different preferences. However, there are no reliable publications confirming the role of magnesium deficiency in the diet as a factor causing migraine attacks. It also seems interesting to deepen the research on the administration of high doses of magnesium intravenously during migraine attacks. The aim of the study was to discuss the probable mechanisms of correlation of magnesium deficiency with migraine, as well as to present the current clinical proposals for the use of various magnesium preparations in complementary or substitute pharmacotherapy of migraine. The summary of the results of research and clinical observations to date gives hope of finding a trigger for migraine attacks (especially migraine with aura), which may turn out to be easy to diagnose and eliminate with pharmacological and dietary supplementation.

Migraine and Its Association with Hyperactivity of Cell Membranes in the Course of Latent Magnesium Deficiency-Preliminary Study of the Importance of the Latent Tetany Presence in the Migraine Pathogenesis.

So far, there is no consistent and convincing theory explaining the pathogenesis of migraines. Vascular disorders, the effect of oxidative stress on neurons, and the contribution of magnesium-calcium deficiencies in triggering cortical depression and abnormal glutaminergic neurotransmission are taken into account. However, there are no reliable publications confirming the role of dietary deficits of magnesium and latent tetany as factors triggering migraine attacks. The aim of the study was to evaluate the influence of latent magnesium deficiency assessed with the electrophysiological tetany test on the course of migraine. The study included: a group of 35 patients (29 women and six men; in mean age 41 years) with migraine and a control group of 24 (17 women and seven men; in mean age 39 years) healthy volunteers. Migraine diagnosis was based on the International Headache Society criteria, 3rd edition. All patients and controls after full general and neurological examination were subjected to a standard electrophysiological ischemic tetany test. Moreover, the level of magnesium in blood serum was tested and was in the normal range in all patients. Then, the incidence of a positive tetany EMG test results in the migraine group and the results in the subgroups with and without aura were compared to the results in the control group. Moreover, the relationship between clinical markers of spasmophilia and the results of the tetany test was investigated in the migraine group. As well as the relationship between migraine frequency and tetany test results. There was no statistically significant difference in the occurrence of the electrophysiological exponent of spasmophilia between the migraine and control group. Neither correlation between the occurrence of clinical symptoms nor the frequency of migraine attacks and the results of the tetany test was stated (p > 0.05). However, there was an apparent statistical difference between the subgroup of migraine patients with aura in relation to the control group (p < 0.05). The result raises hope to find a trigger for migraine attacks of this clinical form, the more that this factor may turn out to be easy to supplement with dietary supplementation.

Variability in melatonin concentration in blood serum of patients with episodic migraine: a pilot study.

AIM OF STUDY: This study was aimed at assessing the possible effect of melatonin concentration on migraine. The serum concentration profile of melatonin in patients with diagnosed episodic migraine in the interictal period was compared to the profile in patients without migraine. Then, a correlation between the frequency and duration of migraine attacks, and the possible relationship between these parameters and melatonin levels in individual patients, was established. CLINICAL RATIONALE FOR STUDY: Melatonin secretion is related to migraine pathophysiology in many different ways. MATERIALS AND METHODS: The study was conducted in a group of 58 subjects (48 women and 10 men). The study group comprised 29 patients (24 women and five men) diagnosed with migraine according to the International Classification of Headache Disorders (ICHD-3 beta), within the framework of the Outpatient Clinic at Bielanski Hospital in Warsaw and the Clinical Department of Neurology of the 2nd Faculty of Medicine (now known as the Faculty of Medical Sciences) at the Medical University of Warsaw, Poland. The control group consisted of 29 subjects (24 women and five men) with no headache. Blood samples for the determination of melatonin were collected at midnight, 2am, 3am, 4am and 6am. Melatonin level in a frozen serum of venous blood was determined by a radio-immuno-enzymatic method at the Department of Histology and Embryology of the Faculty of Veterinary Medicine at the University of Warmia and Mazury in Olsztyn, Poland. RESULTS: No statistically significant differences between the levels of melatonin and the averaged advances of melatonin profiles were observed in the examined and the control group. There were demonstrated medium negative correlations between the maximum value of melatonin and the duration of migraine (R = -0.4, p = 0.03). There were also observed statistically significant differences (p = 0.01) between the averaged advances of melatonin profiles, depending on the duration of migraine. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study showed no abnormalities of melatonin secretion in patients with migraine during the interictal period. The results of studies available in the literature depend on the nature of the headache (episodic or chronic) and the time of measuring the concentration of melatonin (during a headache attack or in an interictal period).

Low-symptomatic skeletal muscle disease in patients with a cardiac disease - Diagnostic approach in skeletal muscle laminopathies.

Mild skeletal muscle symptoms might be accompanied with severe cardiac disease, sometimes indicating a serious inherited disorder. Very often it is a cardiologist who refers a patient with cardiomyopathy and/or cardiac arrhythmia and discrete muscle disease for neurological consultation, which helps to establish a proper diagnosis. Here we present three families in which a diagnosis of skeletal muscle laminopathy was made after careful examination of the members, who presented with cardiac arrhythmia and/or heart failure and a mild skeletal muscle disease, which together with positive family history allowed to direct the molecular diagnostics and then provide appropriate treatment and counseling.

Evaluation of activities of daily living in patients with slowly progressive neuromuscular diseases.

Slowly progressive neuromuscular diseases include but are not limited to: facioscapulohumeral muscular dystrophy (FSHD) and limb-girdle muscular dystrophy (LGMD), hereditary motor and sensory neuropathy (HMSN) and spinal muscular atrophy type III (SMA3). The purpose of this study is to present an evaluation of basic and complex activities of daily living in patients suffering from these diseases. The study was conducted on a group of 58 Polish patients: 25 patients with HMSN, 19 with LGMD and FSHD and 14 with SMA3. The research instrument consisted of two parts: a specially designed questionnaire and Nottingham Extended ADL Index. The survey was voluntary, anonymous and self-administered. In our study the highest scores on the NEADL scale were achieved by HMSN patients, and the lowest by patients with SMA3. The research revealed statistically significant differences between all the groups in the total number of points achieved on NEADL scale. The study revealed that for most respondents the most difficult tasks were those in the area of 'mobility'. It is consistent with reports in the literature, which confirm that out of the slowly progressive neuromuscular diseases included in this research, SMA3 is a disease leading to the biggest limitations in performing the activities of everyday life.

The role of genetic factors and pre- and perinatal influences in the etiology of autism spectrum disorders - indications for genetic referral. / Znaczenie czynników genetycznych oraz przed- i okoloporodowych w etiologii zaburzen ze spektrum autyzmu - wskazania do konsultacji genetycznej.

Autism spectrum disorders (ASD) are caused by disruptions in early stages of central nervous system development and are usually diagnosed in first years of life. Despite common features such as impairment of socio-communicative development and stereotypical behaviours, ASD are characterised by heterogeneous course and clinical picture. The most important aetiological factors comprise genetic and environmental influences acting at prenatal, perinatal and neonatal period. The role of rare variants with large effect i.e. copy number variants in genes regulating synapse formation and intrasynaptic connections is emphasised. Common variants with small effect may also be involved, i.e. polymorphisms in genes encoding prosocial peptides system - oxytocin and vasopressin. The environmental factors may include harmful effects acting during pregnancy and labour, however their specificity until now is not confirmed, and in some of them a primary genetic origin cannot be excluded. In several instances, especially with comorbid disorders - intellectual disability, epilepsy and dysmorphias - a detailed molecular diagnostics is warranted, which currently may elucidate the genetic background of disorder in about 20% of cases.

Emery-Dreifuss muscular dystrophy type 2 associated (?) with mild peripheral polyneuropathy.

In recent years numerous mutations in the LMNA gene encoding lamin A/C were shown to segregate with a wide spectrum of phenotypes. A recurrent p.R377H mutation in the LMNA gene was reported in patients with Emery-Dreifuss dystrophy (EDMD2) with various ethnic backgrounds. We present a patient with EDMD2 caused by a p.R377H mutation, associated with mild peripheral polyneuropathy. The analysis of peripheral myelin protein 22 (PMP22), ganglioside induced differentiation-associated protein 1 (GDAP1), gap junction ß-1 protein (GJB1), and myelin protein zero (MPZ) genes did not reveal mutations; however, we identified a new sequence intronic variant in the mitofusin 2 (MFN2) gene of unknown pathogenic significance. A complex phenotype in the presented patient might depend either on single mutation in the LMNA gene or on bigenic defect; therefore, a wide genetic investigation is needed to elucidate the molecular background of EDMD2/polyneuropathy in this case.

A severe recessive and a mild dominant form of Charcot-Marie-Tooth disease associated with a newly identified Glu222Lys GDAP1 gene mutation.

Charcot-Marie-Tooth (CMT) disease caused by mutations in the GDAP1 gene has been shown to be inherited via traits that may be either autosomal recessive (in the majority of cases) [CMT4A] or autosomal dominant [CMT2K]. CMT4A disease is characterized by an early onset, and a severe clinical course often leading to a loss of ambulation, whereas CMT2K is characterized by a mild clinical course of benign axonal neuropathy beginning even in the 6th decade of life. Clinical data from a GDAP1 mutated patient suggests that the presence of a particular mutation is associated with a certain trait of inheritance. The association of a particular GDAP1 gene mutation and a dominant or recessive trait of inheritance is of special importance for genetic counseling and the prenatal diagnostics as regards severe forms of CMT. In the present study we report on two CMT families in which a newly identified Glu222Lys mutation within the GDAP1 gene segregates both in autosomal dominant and recessive traits. Our study shows that at least some GDAP1 gene mutations may segregate with the CMT phenotype as both dominant and recessive traits. Thus, genetic counseling for CMT4A/CMT2K families requires more extensive data on GDAP1 phenotype-genotype correlations.

[Electrophysiological evaluation of peripheral nerves in ischemic lower limbs]. / Ocena elektrofizjologiczna nerwów obwodowych w niedokrwieniu konczyn dolnych.

The study concerned electrophysiological parameters during stimulation of peroneal, tibial, sural and femoral nerves of patients with ischemia of lower limbs. The disease was clinically verified and confirmed on the basis of an ankle-brachial index (ABI). Peripheral nerves injuries caused by other reasons have been excluded from the research. For statistical evaluation of the material, groups of 86 chronic ischemic limbs (ABI < 0.91) and 57 healthy ones (ABI > 0.99) were created. All observation allowed to recognize an axonal-demyelization neuropathy, with strong axonal element. Changes concerned mainly long nerves. Coexistence of spinal roots damage was often (75.4%) noticeable. The correlation between degree of ischemia (ABI) and studied parameters has not been noticed. We described 5 cases of acute ischemia. There was no significant improvement after surgical or conservative therapy.