Aleksandra Kacar

Impairment of cortical inhibition in writer's cramp as revealed by changes in electromyographic silent period after transcranial magnetic stimulation.

Changes in silent period (SP) duration following transcranial magnetic stimulation (TMS) set at 20% above the motor threshold were studied in six subjects suffering from writers cramp, while performing dystonic movement and during voluntary isometric contraction of the muscles mostly involved in the dystonic movement. Dependency of SP duration on the intensity of preceding muscle contraction was compared on both affected and healthy side. In all subjects SP duration during dystonic contraction was shorter than during voluntary contraction of the similar strength performed with the same hand. Also, in five subjects, SP duration during dystonic contraction was shorter than during voluntary contraction of the similar strength performed with the healthy hand. In addition, the SP duration on the affected side was negatively associated with the intensity of the preceding contraction (i.e. the stronger contraction the shorter SP), while on the healthy side it was not the case. It is concluded that central inhibitory mechanisms are abnormal in writers cramp.

History of exposure to dopaminergic medication does not affect motor cortex plasticity and excitability in Parkinson’s disease

OBJECTIVE Little is known whether and how chronic exposure to dopaminergic treatment alters physiological mechanisms in Parkinsons disease (PD). METHODS Two clinically similar groups of PD patients, one consisting of drug-naïve patients and another of patients already on chronic dopaminergic medication (when off medication), were compared to each other and to a control group. Plasticity and excitability of the hand primary motor cortex of the more affected side were evaluated using transcranial magnetic stimulation (TMS) techniques. RESULTS There was little difference between two patient groups, and both groups showed similar differences in comparison to controls: decreased facilitatory sensory-motor plasticity (as measured by paired associative stimulation [PAS] protocol), impaired short-interval intracortical inhibition (SICI), and diminished slope of input-output curves at higher TMS intensities. The exception was that 30 min after PAS, intracortical facilitation (ICF) was significantly reduced in drug-naïve patients, whereas it changed much less in other two groups. CONCLUSIONS Chronic exposure to dopaminergic drugs does not affect substantially the features of motor cortex excitability and plasticity in PD. There is little interaction between plasticity and excitability features of motor cortex in PD. SIGNIFICANCE Reduced response to facilitatory PAS protocol, reduced SICI, and reduced slope of the input-output curve at higher TMS pulse intensities, seem to be physiological markers for the presence of the pathological disease process in PD. Long term treatment does not seem to change the underlying physiology of the disease.

Changes in Cortical Inhibition During Task-Specific Contractions in Primary Writing Tremor Patients

Primary writing tremor (PWT) is a rare disease of unknown pathophysiology. We studied changes in silent period (SP) duration, after transcranial magnetic stimulation (TMS), set at 20% above the motor threshold in 6 PWT patients and 7 healthy control subjects. SP duration was tested during a task‐specific act, i.e., writing that induced tremor in all patients in the affected hand (Wr); nonspecific voluntary contraction of intensity, matching that developed during writing (VCWr); and during near maximal voluntary contraction (VCNmax). There were no differences in SP duration during Wr and VCWr contraction on the right affected side or between sides in both PWT patients and control subjects, nor between the groups. However, during VCNmax, SP significantly shortened on both sides in PWT patients, whereas there were no changes in control subjects. Although it appears that inhibitory mechanism are not directly involved in the generation of the tremulous activity, the shortening of SP indicates that central inhibitory mechanisms are affected in PWT patients. Therefore, whereas the underlying pathophysiological mechanisms in PWT and writers cramp may share common features, the results indicate that PWT is not a variant of focal task‐specific dystonia but rather a separate nosological entity.

Peripheral neuropathy in patients with myotonic dystrophy type 1

Abstract Objectives: To assess the frequency and type of peripheral neuropathy (PNP) in patients with myotonic dystrophy type 1 (DM1), as well as to identify factors that may be associated with this abnormality. Methods: This study comprised 111 adult patients with DM1. Nerve conduction study was performed on sural, peroneal and median nerves of both limbs. Results: PNP was somewhat more frequent in DM1 patients with glucose intolerance and diabetes mellitus (66·7 vs 33·7%, P = 0·05). In DM1 patients with no glucose intolerance, diabetes mellitus and thyroid dysfunction, the most frequent type of PNP was demyelinating (70·0%) and motor (83·3%). PNP was more frequent in males (45·7 vs 20·9%, P<0·05). Patients with PNP were older (43·7±7·3 vs 39·6±9·6 years, P<0·05) and had a longer duration of DM1 compared to those without PNP (18·6±9·9 vs 12·7±8·3 years, P<0·01). DM1 patients with PNP had a higher body mass index) (24·9±5·5 vs 22·4±4·2 kg/cm2, P<0·05), higher triglycerides (3·1±3·3 vs 1·8±0·8 mmol/l, P<0·01), total cholesterol (6·2±1·4 vs 5·4±1·1 mmol/l) and LDL cholesterol (4·3±1·2 vs 3·4±1·0, P<0·05). Achilles reflexes were absent in 76·9% patients with PNP and in 51·9% patients without PNP (P<0·05). Patellar reflexes and muscle strength were similar in both groups (P>0·05). Conclusions: PNP was present in one-third of DM1 patients. The most common type was motor and demyelinating PNP. Our results suggest the association between the presence of peripheral nerve impairment in DM1 and male gender, age, duration of disease and certain metabolic parameters.

Variability of multisystemic features in myotonic dystrophy type 1 – lessons from Serbian registry

Abstract Background: Myotonic dystrophy type 1 (DM1) is a rare disease. Creating registry for such a disease is of outstanding importance since it provides us with a full spectrum of the disorder. Aim: To assess variability of different multisystemic features in a large cohort of patients with DM1. Patients and Method: Data from the Serbian registry for myotonic dystrophies were used in the study. Final number of included DM1 subjects was 275. Results: Registry included 53.8% of male patients. Age at enrollment was 47.2 ± 9.9 years, mean disease duration 20.4 ± 9.9 years, and mean CTG repeats number 598.3 ± 269.8.Progression of muscle weakness was pretty slow, slower in proximal than distal muscles, and slower in arms than in legs. Severe ECG abnormality was found in 25.0% of patients and pacemaker was implanted in 9.5%. Lens opacities were observed in 83.5% of DM1 patients and 35.3% had ocular hypotony. Metabolic disturbances were very common, while 19.5% of patients had hypokalemia and 37.8% hypochloremia. Sterility was found in 20.5% of males and 4.1% of females. Cholelithiasis was found in 36.4% of patients and constipation in 29.9%. Conclusions: We defined the most common characteristics of our DM1 patients and observed some treatable symptoms that have been neglected previously. Certain findings deserve further investigations in terms of their causes and consequences. Besides this, presented data analysis directs us to make further improvements of the registry.

Neuromuscular disease-specific questionnaire to assess quality of life in patients with chronic inflammatory demyelinating polyradiculoneuropathy: Kacar et al

To date, generic questionnaires have been used to investigate quality of life (QoL) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients. Although these measures are very useful, they are not usually precise enough to measure all specific characteristics of the disease. Our aim was to investigate QoL using the neuromuscular disease‐specific questionnaire (individualized neuromuscular quality of life, INQoL) in a large cohort of patients with CIDP. Our study comprised 106 patients diagnosed with CIDP. INQoL questionnaire, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, Visual Analogue Pain Scale, Beck Depression Inventory, and Krupps Fatigue Severity Scale were used in our study. Physical domains of INQoL were more affected than mental, and the overall score was 57 ± 25. Significant predictors of higher INQoL score in our patients with CIDP were severe fatigue (β = 0.35, p < 0.01), higher INCAT disability score at time of testing (β = 0.29, p < 0.01), and being unemployed/retired (β = 0.22, p < 0.05). QoL was reduced in our cohort of CIDP patients, which was more pronounced in physical segments. Patients with fatigue, more severe disability, and unemployed/retired need special attention of neurologists because they could be at greater risk to have worse QoL.

Prospective measurement of quality of life in myotonic dystrophy type 1

Generic patient reported outcome measures have had varied success in tracking QoL in myotonic dystrophy type 1 (DM1).

Graphospasm - clinical presentation, etiology and the course of disease: Analysis of 30 cases

INTRODUCTION Dystonia, as prolonged, involuntary muscle contraction, causes torsion, repetitive movements and abnormal body position. In so far only a part of body is affected by dystonic movement, it is the question of focal dystonia, which is called writers cramp if the arm is involved. OBJECTIVE The objective of the study was to present the specific clinical features of patients with task-specific dystonia, who were diagnosed, treated and followed up at the Institute of Neurology, Clinical Center of Serbia, Belgrade. MATERIAL AND METHODS In the period 1995-2003, 30 patients with task-specific dystonia were treated at the Institute of Neurology, CCS, who met the adopted criteria for diagnosis. The severity of the diseases was tested by estimating the ability of patient to write the test sentence per time unit, as well as by means of scale for measuring different disabilities, ranging from 0-16 (Marsden-Fahn). Depression, anxiety and obsessiveness were tested by Becks scale, Hamiltons depression and anxiety scale and Mousdlys obsessiveness scale. Thorough questionnaire focused on clinical details was also used. Besides descriptive statistics, data processing included analysis of variance and Kruskal-Walliss test. RESULTS Thirty patients with diagnosis of task-specific dystonia were analyzed. At the onset of the disease, mean-age was 34.1 years (SD=11.4; 13-58), while the duration of disease at the moment of the examination was 10.3 years (SD=10.6; 1-39). There were 20 males and 10 females (sex ratio 2:1). None of the patients reported any history of trauma of subsequently affected region before the development of discomforts. Twelve patients used their hands for a long time during their professions (writing, playing the instrument, type-writing, etc.). Eight patients were typists (26.6%), four were musicians (13.3%), while the rest of cases (18) had some other occupations that did not necessarily imply long-term use of hands (office worker, engineer, physician, mechanical technician, etc.). Twelve patients had simple task-specific dystonia (type I) (40%), ten cases manifested progressive diseases (type II) (33.3%), while the others suffered from dystonia that was present at rest (type III). Two patients had positive family history. DYT 1 mutation was verified in one of them. Depression, anxiety and obsessiveness were not verifed in our patients. Type of writers cramp was not in correlation with any of the tested parameters except with the age at the onset of the disease, severity of disease according to Marsdens scale and degree of disability.

Employment status of patients with chronic inflammatory demyelinating polyradiculoneuropathy

It has been previously shown that patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who are unemployed or retired have worse quality of life. The aim of this study was to assess predictors of early retirement in CIDP. One hundred five patients with CIDP were included. Following measures were used: questionnaire on employment status, Medical Research Council Sum Score, INCAT disability score, Beck Depression Inventory, and Krupps Fatigue Severity Scale. At the moment of testing, 2% of patients were students, 15% were employed, 9% were unemployed due to CIDP, 9% were unemployed but not due to CIDP, 28% were retired early due to disability caused by CIDP, and finally 37% were in old‐age pension. Mean age when patients retired due to CIDP was 50 ± 8 years. Mean time from CIDP onset to retirement was 2.7 ± 2.3 years. Older age at onset, lower education, and more severe weakness at the time of diagnosis were significant predictors of early retirement due to CIDP. Retired patients were 12 times more likely to suffer from depression, compared to employed patients (OR = 12.2, 95% CI = 1.41‐100, P < 0.01), and eight times more likely to have fatigue (OR = 8.2, 95% CI = 1.89‐35.82, P < 0.01). Older patients with lower education and more severe weakness at the time of diagnosis were most likely retired due to CIDP. Early retirement was associated with depression and fatigue. Therefore, maintaining employment should be an important aim in the management of CIDP patients.

Changes in cortical excitability during paired associative stimulation in Parkinson's disease patients and healthy subjects

Paired associative stimulation (PAS) combines repetitive peripheral nerve stimulation with motor cortex (M1) transcranial magnetic stimulation (TMS), to induce plastic-like changes of cortical excitability. While much attention has been dedicated to post-PAS effects little is known about processes during PAS. We compared the time-course of changes in M1 excitability during standard facilitatory PAS intervention among patients with Parkinsons disease (PD), known to have diminished post-PAS response, and healthy subjects. Compared to baseline pre-PAS MEPs, conditioned MEPs during PAS decreased significantly in both groups. The decrease was significantly larger in healthy subjects than in PD patients, regardless whether patients were drug-naïve or not. Although post-PAS excitability increase was also larger in healthy subjects than in PD patients, there was no significant correlation between the two phenomena, i.e. the extent of MEP decrease during PAS and the extent of the post-PAS excitability increase. The results highlight an apparent physiological paradox that repetitive application of an inhibitory stimulation pattern leads to subsequent prolonged facilitation, thus broadening the understanding of the phenomenology of PAS response. Results also suggest that in PD cortical circuits involved in conveying inhibition during PAS, are impaired at the clinical onset of the disease and are not influenced by subsequent PD treatment.