Clinical Neuroscience

[Diagnosis and therapy of mitochondrial diseases]

PÁL Endre

JULY 30, 2012

Clinical Neuroscience - 2012;65(07-08)

[Mitochondrial diseases are a significant part of neuromuscular diseases. Majority of them is multisystemic disorder. The diagnosis can be established in more and more cases. Beyond the routine neurological examination imaging methods (MRI and MR-spectroscopy) and electrophysiology (EMG, ENG, EEG, evoked potential tests) might be helpful in setting the diagnosis. Raised blood lactate level supports the diagnosis. Muscle biopsy demonstrates mitochondrial abnormalities in the majority of cases. The positivity of genetic tests is low, because the amount of mitochondrial DNA alterations is different in tissues. Therefore other tissue than blood (mainly muscle) is necessary for genetic tests. The other reason is that the respiratory chain is under double -mitochondrial and nuclear - genetic control, and testing the nuclear genes are available only in selected laboratories. The treatment is limited, mainly symptomatic.]



Further articles in this publication

Clinical Neuroscience

[Endoscopic, posterior transseptal pituitary surgery - Learning curve of the surgical technique and equipment in 61 operations]


[Introduction - The removal of hypophyseal tumor by transsphenoidal pituitary surgery using microsurgical instruments was first performed over 100 years ago. Operating techniques for this surgery are constantly being renewed, first by using a microscope and later on with the use of an endoscop. The authors provide an overview of the minimal invasive posterior transseptal-transsphenoidal aproach with the combined utilization of classical techniques with the assistance of the endoscop. Method - Sixty-one patients (33 female, 28 male, 21-84 yrs) were treated for sellar region tumor resection using an endonasal transsphenoidal aproach with the help of an endoscop. Follow ups were performed within 2-21 months. Results - Total tumor resection was successful in 91.8%, and partial resection in 8.2% of the patients. The rate of complications using the endoscop method was not higher compared to that of the classical microscopic method. There was no major bleeding in any of the cases. Adverse events such as minor epistaxis occurred in 4.9%, transitional diabetes insipidus in 6.5%, inraoperative CSF leak in 16.67%, postoperative CSF leak in 11.5% and meningitis in 8.2% of the patients. After the operation the pathological hormonal production stoped in all patients except in two patients who were acromegalic. However their GH level normalized and they did not require further treatment, the IGF-1 still remained high. Conclusion - The success of the surgical treatment is based on both, the proficient pre- and postoperative endocrinological care, and the minimal invasive surgical technique. The endoscop was used partially or continuously during the operation for better visualization of the operation field in multiple angles (30°, 45°). It was useful in differentiating between normal and tumorous glandular tissue, and also offered an enhanced view of the intrasellar (via hydroscopy) and parasellar region. Moreover the endoscopic method is able to decrease the operating time, reduce blood loss. In different stages of the surgery, depending on the anatomical and pathological situation, switching back and forth from microscope to endoscop technique, gives us the benefit of a clearer view in each situation.]

Clinical Neuroscience



[Neurophobia is the fear of neurological diseases. Its main symptom is that medical students and young doctors are not able to utilize their basic neurological knowledge at the bedside. According to statistics, every second student suffers from neurophobia. This attitude could explain why in the last two decades less and less young doctors wanted to become neurologist. Medical students complain that they receive no instructions, and are afraid of loosing their interest and of facing the failure of their competency. The hardship of neurology was explained by the insufficient knowledge of anatomy and the infrequent encounter with patients. Even general practitioners have anxiety about neurological patients. The loss of interest in neurosciences seems to associate with insensitivity of human-centered culture and corruption of empathic thinking. The burnout syndrome of medical doctors and students can be explained by stress, loss of respect, permanent competition, independency that interferes with responsibility, stiff hierarchy of medical society, fear of diagnostic failures and of economical difficulties. The scores of depression in female students were higher than in male. The idea of the “good neurologist” has been changed. The business oriented care, the shortage of time, and the financial restrictions corroded the conventional practice and ceased the vocational idealism. At present, personal teaching is going to transform into impersonal multimedia learning. Because of the drastic change of values, the age of inner-oriented professionals has terminated also in the medicine. Medical doctors follow even less the traditional troll of professional behavior, but according the social demands, they choose their specialization for subsistence. The highly esteemed social status of neurologists and psychiatrists is going to sink in Europe. To reduce neurophobia it would be desirable 1. to introduce neurology training in the early years of medical school; 2. to teach neurology in all semesters, 3. to assure the effective teaching of neuro-anatomy and physiology, 4. to organize more one-to-one teacher-student communication. In the United States, residents participate in teaching during their residency training. To master neurology dedicated teachers are necessary whom neurology residents ought to meet personally with optimal frequency. However, these requirements seem to fail because of the chiefly technical characters of the actual reforms.]

Clinical Neuroscience

[Recommendations for a brief international cognitive assessment for multiple sclerosis]

BENCSIK Krisztina

Clinical Neuroscience

[Results of intrathecal baclofen therapy on spasticity in patients with brain injury]

DÉNES Zoltán, KLAUBER András, BOTH Béla, ERÕSS Loránd

[Objectives - To evaluate the results of intrathecal baclofen (ITB) therapy on the spasticity in patients with brain injury. Method - Retrospective study in Brain Injury Rehabilitation Unit between January 2001 and December 2010. Results - During the last ten years, in our unit 13 patients were involved into ITB therapy on severe spasticity, after brain injury, while more than 100 Baclofen pumps were implantated in Hungary with Hungary with coordination of the Multidisciplinary Team. ITB therapy was indicated in severe spasticity developed after seven cases of traumatic brain injuries, five cases of strokes and one case of anoxic brain injury. The mean age of patients was 26 years (18- 52). At the time of pump implantation three patients were in vegetative state. The shortest period elapsed between the brain injury and pump implantation was three months and the longest period was nine years, mean 15 months. Baclofen pump had to be changed in six cases after six years, and was removed in three cases due to decreasing spasticity. Catheter revision was performed in two cases due to flow problem. We had no complication in association with ITB therapy. Conclusions - Intrathecal baclofen therapy seems to be an effective and safe treatment in patients with severe spasticity of cerebral origin. We suggest team (neurosurgeon and rehabilitation professionals) decision in a spasticity center before involving the patient into ITB therapy, and follow up in the rehabilitation unit. The severity of spasticity as a consequence of brain injury can change during years and it is necessery to follow it with dosage and dynamics of baclofen therapy. Baclofen pump removal is suggested if the ITB therapy is further not reasonable.]

Clinical Neuroscience

[Treatment of dystonia by deep brain stimulation: a summary of 40 cases]

DELI Gabriella, BALÁS István, KOMOLY Sámuel, DÓCZI Tamás, JANSZKY József, ILLÉS Zsolt, ASCHERMANN Zsuzsanna, TASNÁDI Emese, NAGY Ferenc, PFUND Zoltán, BÓNÉ Beáta, BOSNYÁK Edit, KULIFFAY Zsolt, SZIJJÁRTÓ Gábo

[Background - Bilateral pallidal deep brain stimulation (DBS) is an established treatment option for primary generalized and segmental dystonia. In the present study we evaluated the results of our dystonia patients treated by DBS. Methods - The surgical results of forty consecutive dystonia patients underwent DBS implantation were analyzed (age: 43.7±17.7 years; sex: 22 men; etiology: 24 primary and 16 secondary dystonia; topography: 24 generalized, 12 segmental and four hemidystonia; disease duration: 16.1±9.3 years). Severity of dystonia measured by Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and health-related quality of life measured by EQ-5D scale were obtained preoperatively and compared to the scores obtained at postoperative six months and subsequent yearly follow-ups. The average follow-up lasted 2.5 years (median, 0.5-8 years). In all cases the BFMDRS scores were re-evaluated by a rater blinded to the treatment. Treatment responsiveness was defined as an at least 25% improvement on the BFMDRS scores. Non-parametric Mann-Whitney, McNemar and Kruskal-Wallis tests were applied to test statistical significance. Results - Severity of dystonia improved from 31 to 10 points (median, 68% improvement, p<0.01) in the primary dystonia group, whereas in secondary dystonia these changes were statistically insignificant (improvement from 40 to 31.5 points, 21.2%, p>0.05). However, the health-related quality of life significantly improved in both groups (primary dystonia: 0.378 vs. 0.788 and secondary dystonia: 0.110 vs. 0.388, p<0.01). Significantly more patients in the primary dystonia group responded to DBS treatment than those in the secondary dystonia group (83.3% vs. 37.5%, p<0.01). Conclusion - Our results are in accordance with previously published international findings demonstrating that DBS is a highly effective and long-lasting treatment option for primary dystonia. DBS is considerably less efficient in secondary dystonia; however, it still has a high impact on the quality of life presumably due to its pain-relieving effect.]

All articles in the issue

Related contents

Hungarian Radiology

[Esophageal diverticula in mixed connective tissue disease]

SZÁNTÓ Dezső, SZŰCS Gabriella, DITRÓI Edit

[INTRODUCTION - The functional and morphological changes of oesophagus occur in two third of mixed connective tissue disease patients according to the literature. CASE REPORT - We report three cases of 27, 39 and 48 year old women suffering of lateral pharyngoesophageal, epibronchial and epiphrenic diverticula associated with connective tissue disease. Diverticula had an average diameter of 3.8 cm (maximal diameters: 7.2-8 cm). The esophageal pouches produced dysphagia, dystonia, motility disorders, food stagnation and vomiting, retrosternal burning sensation and tachyarrythmia after 5-16 month's latency period. In one patient pneumoesophagus also evolved. The high serum enzyme levels and proximal electromyogram proved the presence of polymyositis. CONCLUSION - The localization, number and the size of esophageal diverticula are determined by the interstitial myopathy.]

Lege Artis Medicinae



[Statins, specific inhibitors of the 3-hydroxy-3-methylglutaryl- coenzyme A (HMG-CoA), decrease significantly pathologically elevated cholesterol levels. The effectiveness and the side effects of the different analogs depend on their inhibitory potency, lipid solubility, active uptake into the liver cells and on the difference in their metabolism. The statins can be divided into three groups on the basis of their clinical effectiveness: the highly effective agents are rosuvastatin and atorvastatin; simvastatin exhibits an intermediate activity, while lovastatin, pravastatin and fluvastatin are the least active drugs. The main metabolic pathways of the statins are oxidation and glucoronidation and finally the spontaneous inactivation by lactone ring formation of the glucoronidated products. Gemfibrozil increases the plasma level of all statin analogs by inhibiting the activity of UGT1A1 and UGT1A3 isoenzymes of the UDPglucoronosyltransferase. Therefore, when a statinfibrate combination is needed, fenofibrate and bezafibrate are recommended, the metabolism of which are linked to other UGT isoenzymes. Similarly elevated plasma levels are produced by inhibiting the specific cytochrome isoforms participating in the oxidation of a particular statin. Severe side effects are rarely observed. The most frequent adverse reaction is the development of myopathy of various severity. Using various statins rhabdomyolysis occurred in 0.0-0.3 cases /100 000 statin prescriptions if the already withdrawn cerivastatin is not considered. The statin+gemfibrozil combination increases the number of rhabdomyolysis approximately tenfold. The long-term benefit of statin therapy far exceeds the risk of the treatment. For achieving very low lipid target values even the most effective statins must be used in high doses. Nevertheless, this goal cannot be reached in about 20% of the cases. High dose statin treatment should be administered with the gradual increase of the dose, tight control of the patients and by meticulously selecting the drugs given simultaneously. Further development can be expected from the application of agents with new mechanisms of action, such as the cholesterol uptake inhibitor ezetimibe.]

Lege Artis Medicinae

[Necrotising autoimmune myopathy showing dermatomyositis symptoms during persistent statin treatment]

TIHANYI László, SÜTŐ Gábor, VERESS Gábor

[INTRODUCTION - Dermatomyositis is an idiopathic autoimmune disease. Diagnosis has to be confirmed by biopsy, because clinical symptoms can be similar to those in other myopathies. CASE REPORT - The authors describe the development of dermatomyositis in a 59- year-old man. The patient had a heart attack in 1988. He had been taking simvastatin for three years and atorvastatin since 2002. In June 2008 he complained of myalgia and weakness, became physically very inactive but visited our specialist only half a year later. Laboratory examinations showed a substantial increase of CK, CKMB, LDH and HBDH with troponin T positivity (troponin I was negative). A subsequent biopsy confirmed dermatomyositis. Treatment with azatioprine and methylprednisolone and suspending statin therapy resulted in the regression of his clinical symptoms, his muscles gradually became stronger and his laboratory values normalised. CONCLUSION - During statin treatment in 5% of the cases myopathy can occur, which might develop into amore severe inflammatory disorder.]