2006, Vol 6, No 1
Pharmacological diagnosis of autonomic pupil denervation
Aktualn Neurol 2006, 6 (1), p. 13-23

Pharmacological tests are widely used in evaluation of autonomic pupil denervation in Western Europe and United States. These tests allow to localize the level of lesion of pupil’s autonomic pathways. The application of such tests can reduce the number of the other necessary and expensive diagnostic tests, including imaging studies. Such approach is of special value in diagnosing sympathetic pupil denervation, due to complexity of the sympathetic pathways. The use of pharmacological test in diagnosis of pupil denervation is limited in Poland due to unavailability of the necessary substances. The lack of availability of adequate pharmacological substances is the main factor limiting this form of diagnostics. The most useful tests used in diagnostics of sympathetic pupil denervation are the hydroxyamphetamine and cocaine tests. The application of hydroxyamphetamine enables the investigator to distinguish first or second neuron damage from the third neuron injury. However, the cocaine test allows to distinguish between the first neuron damage and the injury of the second or third sympathetic neuron innervating the pupil. Thus, only application of both tests – one after the other – allows us to precisely locate the site of damage in the sympathetic pathway. Unfortunately, the cocaine solution is not available in Europe (is only used in the USA). In case of suspected damage of parasympathetic pathway innervating the pupil, the most used is the carbachol test. Unfortunately, this substance is not perfect, because after application to the eye, the pupil with damaged second parasympathetic neuron or the pupil in a patient with Holmes-Adie syndrome act exactly the same. Thus it is only possible to distinguish between the first parasympathetic neuron damage and second neuron damage or Holmes-Adie syndrome. The pilocarpine test enables the investigators to distinguish the pharmacological blockade of cholinergic receptors in synapse from all other possible causes of pathological pupil dilatation. 

Keywords: autonomic pupil denervation, pharmacological tests, anisocoria, Holmes-Adie syndrome, Horner syndrome, sympathetic pathway innervating the pupil, parasympathetic pathway innervating the pupil
The role of homocysteine in pathology of some neurological diseases
Aktualn Neurol 2006, 6 (1), p. 62-66

Lately the role of homocysteine in pathology of diseases, also neurological seems to be very interesting. Homocysteine is an amino acid containing thiol group, produced in body by demethylation of methionine. An important role in its metabolism play vitamins from group B (vitamin B6 and B12), folic acid and enzymes: reductase and synthase. The level of homocysteine depends on genetic and congenital factors. Normal concentration of homocysteine in serum for people under 60 years old is 5-15 mmol/l, for older it is higher. Recently there was found the correlation between the excess of homocysteine and the risk of vascular diseases, dementia. It is also interesting if the level of homocysteine changes in patients with Parkinson’s disease. It can also be teratogenic. It was found that in epileptic patients the level of homocysteine is higher. Antiepileptic drugs which induce cytochrome P450 cause increase in homocysteine levels. 

Keywords: homocysteine, hyperhomocysteinemia, metabolism, epilepsy, anticonvulsants
Multiple system atrophy type C (MSA-C) – clinical and radiological aspects, case report
Aktualn Neurol 2006, 6 (1), p. 48-53

Multiple system atrophy (MSA) is relatively rare degenerative disease of the central nervous system. The prevalence of MSA is about 2-4/100,000. The disease is included to synucleinopathies. The most characteristic neuropathological findings in MSA is argyrophilic glial cytoplasmatic inclusions in oligodendroglia which is composed of α-synuclein and ubiquitin. At present two main forms of the MSA are known: MSA-P and MSA-C. Symptoms of parkinsonism with rigidity and bradykinesia are more typical in MSA-P. Cerebellar signs are more characteristic for MSA-C. Severe autonomic failure, initially or during further clinical course in MSA-P and MSA-C is present in most patients. The main symptoms of autonomic failure are orthostatic hypotension, urinary and less commonly fecal incontinence, impotence. In 1998 consensus on the diagnosis of MSA was established. The authors described a case of 61-year-old women with 3 years symptoms of cerebellar dysfunction followed by Parkinson’s syndrome and autonomic failure. MRI of the brain revealed severe atrophy of the cerebellum and brain stem, and “hot cross bun sign” in pons. Tilt-test confirmed orthostatic hypotension. Treatment with L-dopa and midodrin was moderately effective. The authors described problems of diagnostics, especially role of MRI, and actual problems of epidemiology, pathogenesis and treatment of MSA. 

Keywords: multiple system atrophy, cerebellar atrophy, magnetic resonance, orthostatic hypotension, autonomic failure
An influence of insertion-deletion polymorphism ACE on occurring of cardiovascular system’s diseases and cerebral strokes in assessment of contemporary researches
Aktualn Neurol 2006, 6 (1), p. 44-47

For many years strokes have been a priority research subject. The genetic background of strokes has been of particular interest during the last decade. Intensive research is conducted into the role of polymorphism of the genes whose protein products are involved in the mechanisms of the renin-angiotensin system. Especially interesting is the insertion/deletion (I/D) polymorphism of the gene responsible for the encoding of the angiotensin-converting enzyme (ACE). The enzyme is a dipeptidyl carboxypeptidase transforming angiotensin I (Ang I) into angiotensin II (Ang II) and inactivating bradykinin persons. The gene of ACE was found in chromosome 17 in 1988 year. In 1990 Rigat et al. discovered polymorphism in the area of 3’ 16 intron of the ACE gene, located in band q23 of chromosome 17. DD homozygotes demonstrate a twice increased activity of the enzyme in plasma than II homozygotes, while ID heterozygotes demonstrate intermediate activity values. The percentage of persons with high serum convertase activity (>40 nmol/min) is significantly greater among patients with arterial hypertension than in health persons. According to some researchers, the genotype DD, which is accompanied by higher ACE activity, may be an independent myocardial infarction risk factor, hyperplastic and dilatation cardiomyopathy, sudden cardiac death, and some complications of arterial hypertension. The D allele is a inconsiderable but independent risk factor for ischemic stroke. The investigation led among Polish population is evidenced that DD homozygotes of ACE gene is an independent risk factor for hemorrhage stroke. 

Keywords: cerebral stroke, cardiovascular, polymorphism of angiotensin-converting enzyme, angiotensin II, risk factors
SYMPOSIUM – LAMINOPATHIES. Emery-Dreifuss muscular dystrophy – a cardiologist’s perspective
Aktualn Neurol 2006, 6 (1), p. 39-43

Emery-Dreifuss muscular dystrophy (EDMD) is characterized by various degrees of cardiac involvement. It concerns clinically asymptomatic patients, patients with arrhythmia, and patients with heart failure due to systolic dysfunction. Cardiomyopathy due to EDMD may lead to sudden cardiac death. The variations in the clinical picture of cardiomyopathy in the two forms of EDMD with regard to the type of inheritance is still unclear. The following paper discusses the most recent papers concerning cardiac complications in EDMD and possibilities of their prevention and therapy. Various cardiologic complications in context of different laminopathies have been presented. It lays particular emphasis on the comprehensiveness of treatment and the interdisciplinary nature of the issue. 

Keywords: Emery-Dreifuss muscular dystrophy, cardiomyopathy, arrhythmias, heart failure, laminopathies
SYMPOSIUM – LAMINOPATHIES. Characteristics of nuclear proteins and their association with the laminopathies
Aktualn Neurol 2006, 6 (1), p. 35-38

Genetic studies have now shown that mutations in lamins A/C are present in a heterogenous group of diseases in which they are leading to defects in skeletal muscles, heart, nervous system, fat, skin and bones. The mechanisms leading to the development of laminopathies and the marked differences in phenotypes in the particular laminopathies are not solved, yet. For better understanding the mechanism(s) of laminopathies the localization and structure of lamins, and also the connected with them other nuclear proteins, their synthesis and degradation, their molecular properties, their interactions and probable functions are presented. The lamins, classified already as lamins type A (coded by LMNA gene) and lamins type B (coded by LMN1 and LMN2 genes), are the best characterized nuclear proteins. The structure of other nuclear proteins and their dependence from lamins are still not well defined. The possible mechanism of dilated cardiomyopathy in some laminopathies is also discussed. It is possible that one of the factors responsible for it is an increased susceptibility of cardiomyocytes to mechanical stress because of lamins mutations. Cardiomyopathy may also appear as the consequence of lost nuclei stability in the presence of mutated lamins. The other mechanism may be also the fact that mutated lamins provoke autoimmunologic reactions, cytotoxic against cardiomyocytes. 

Keywords: lamins, other nuclear proteins, structure of nuclear proteins, interactions between lamins and other nuclear proteins, nuclear proteins function
SYMPOSIUM - LAMINOPATHIES. Familial partial lipodystrophy
Aktualn Neurol 2006, 6 (1), p. 32-34

Familiar partial lipodystrophy (Dunnigan type) belongs to group of laminopathies. The main features of the disease include loss of subcutaneous adipose tissue from limbs and trunk, sparring the face and neck, associated with insulin resistant diabetes mellitus and dyslipidemia. Metabolic syndrome is responsible for atherosclerosis which predisposes to coronary heart disease in young people. Hormonal disorders, i.e. polycystic ovarian syndrome and acromegaloid features are found in some patients. Laboratory tests reveal insulin resistance, hyperinsulinemia, hyperglycemia, hypertriglyceridemia and low HDL-cholesterol. Mean FFA level is higher and leptin and adiponectin levels are lower in patients with lipodystrophy type Dunnigan in comparison to healthy people. Women predominance and intrafamilial variability are observed. The disease is characterized by autosomal dominant inheritance. The most frequent mutation is R482W in exon 8, but mutations in exon 11, affecting only lamin A, are also known. Treatment of dyslipidemia and diabetes (diet and pharmacotherapy) are main purposes of therapy. 

Keywords: lipodystrophy, lamin A/C, LMNA, laminopathy, insulin resistance
SYMPOSIUM - LAMINOPATHIES. Laminopathies - an integrating yet still intriguing system
Aktualn Neurol 2006, 6 (1), p. 24-31
Lamins – proteins with intermediate filaments – are components of the internal membrane and internal structures of cell nucleus. Some lamins are encoded by the LMNA gene, located at the long arm of the chromosome 1 – 1q21-23. Mutations of this gene are responsible for several diseases in humans. Some of these diseases have been described long ago – they were considered very rare, they were not diagnosed properly, or their pathogenesis was unclear. Other diseases of this class only recently have appeared in medical handbooks. The key event in our understanding of laminopathies was elucidation in 1994 of the Emery-Dreifuss syndrome, well known to clinicians but rarely described hitherto. It is characterized by the triad of symptoms: early articular contractures (mainly of the cubital, talocrural and cervical vertebral joints), moderate atrophy and weakness of the brachial and peroneal muscle groups, and cardiomyopathy with conduction block, developing at the age of 20. The latter is the main life-threatening factor in Emery-Dreifuss syndrome patients. It became clear that the development of this condition depends on mutation of the STA gene, located at the long arm of the X chromosome (Xq28). The product of this gene is a protein included in the internal nuclear membrane, of molecular weight 34 kDa, called “emerin” in memory of Alan Emery. Its discovery marked a breakthrough in myology (hitherto it was believed that cell nucleus does not play any significant role in human pathology), paving the way for subsequent important discoveries. Among other things, it turned out that the Emery-Dreifuss dystrophy phenotype is not always associated with mutation of the STA gene or with emerin deficit. Growing interest in emerinopathy contributed to gathering of a fairly large number of patients featuring a similar phenotype but entirely different genotypic profile. The most important observation was that some patients phenotypically consistent with the Emery-Dreifuss syndrome, are afflicted with one of the many possible mutations of the LMNA gene. The disease has an autosomal dominant inheritance pattern (rarely autosomal recessive). The product of the LMNA gene are lamins A/C. The gene has 12 exons and depending on location of the mutation, several entirely different syndromes may develop. Thereof, the most important are: 
1.Emery-Dreifuss syndrome, featuring the same triad as the Emery-Dreifuss syndrome associated with emerinopathy; 
2.limb-girdle muscular dystrophy type 1B, characterized by an autosomal dominant pattern of inheritance; 
3.isolated, i.e. idiopathic dilated cardiomyopathy, characterized by an autosomal dominant inheritance pattern; 
4.Charcot-Marie-Tooth disease type 2B with axonal conduction disorders, characterized by an autosomal dominant inheritance pattern; 
5.familial partial lipodystrophy (Dunnigan type), featuring an autosomal dominant inheritance pattern; 
6.mandibuloacral dysplasia (MAD) – a rare yet very severe disease, featuring autosomal recessive inheritance pattern; 
7.Hutchinson-Gilford progeria, characterized by premature senescence of children, featuring autosomal dominant inheritance. 
In the field of laminopathies, which constitute a relatively novel area of research in medicine, we are struck by prominent role of cell nucleus and various mutations at several exons of the LMNA gene, resulting in different nosologic entities. From the clinician’s perspective, laminopathies (or nucleopathies in general) constitute a heterogenous group of hereditary diseases which damage skeletal muscles, cardiac muscle, connective tissue, nerves and bones. An interesting problem is “tissue specificity” of particular laminopathies, in spite of their presence in every tissue. 
Keywords: LMNA, dystrophy, heart, lipodystrophy, senescence
The trapezius muscle atrophy in an 11-year-old boy – a case report
Aktualn Neurol 2006, 6 (1), p. 58-61

The article describes the case of an 11-year-old boy who showed symptoms of the atrophy at his right shoulder. The child, diagnosed with the right shoulder plexus damage (MRI of the right shoulder plexus and the cervical spine was normal), was sent to EMG laboratory in Bydgoszcz. EMG tests did not show any features of the right shoulder plexus damage. The clinical examination showed the wrong position of the shoulder blade, difficulty with shoulder raising and arm abduction. The atrophy was limited to the trapezius muscle. No dysesthesia was observed. A little scar was located at the lateral cervical triangle, behind the sternocleidomastoid muscle. The scar resulted from the removal of the enlarged lymph node. The shoulder muscles atrophy occurred a few months later. Neither the boy nor his mother associated these events. On the basis of clinical examination and EMG tests the boy was diagnosed with the damage of the eleventh right nerve. The lymph nodes removal at the lateral cervical triangle is the most frequent cause of the accessory nerve damage. Other causes include: cranial basis tumors, basal skull and condylar fractures, accessory nerve neurinoma, carotid artery endarterectomy, internal carotid vein catheterizations, pulling, injury, painful atrophy of the shoulder zone muscles. Main problems with treating traumatic (and iatrogenic) damages of the accessory nerve include wrong diagnosis and conservative therapy. The best results of surgical procedures are obtained up to 3-month period following the injury. Differential diagnosis of the shoulder muscle atrophy should take into account the possibility of the accessory nerve damage. 

Keywords: brachial plexus, accessory nerve, eleventh nerve, sternocleidomastoid muscle, trapezius muscle
An in vivo diagnosis of Creutzfeldt-Jakob disease. Case report
Aktualn Neurol 2006, 6 (1), p. 54-57

A rapidly progressing dementia, followed by focal neurological signs and evidence of periodic sharp waves complexes in the EEG may lead to the clinical suspicion of Creutzfeldt-Jakob disease (CJD). Nevertheless the cases of CJD are diagnosed seldom. Patient, a 66-year-old man was admitted to Department of Neurology with progressive disturbances of communication. There was no family history of similar diseases. In the neurological examination aphasia, behavioural abnormalities and grow of muscles tension was found. There were also periodic abnormalities in EEG. The rapidly progressive worsening of consciousness persuaded us to recognizing CJD. We diagnosed him as having CJD as we detected the 14-3-3 neuronal protein in cerebrospinal fluid. Cranial MRI showed mild cerebral atrophy with periventricular white matter hyperintensity in T2-weighted scans. During the observation the contact with patient rapidly worsened and he died after two weeks hospitalisation. The CJD was proven by the typical EEG, neuronal protein in CSF and by autopsy too. This is the one of few cases diagnosed alive. 

Keywords: Creutzfeldt-Jakob disease, rapid course, diagnosed alive, MRI, protein 14-3-3