A 30-year history of MPAN case from Russia.

We present a patient with progressive spastic ataxia, with dystonia and anarthria undiagnosed until detailed genetic analysis revealed an MPAN mutation. Highlighting the worldwide MPAN distribution, a 30year history of absent diagnosis and the impact and cost saving of an early but detailed genetic analysis in complex progressive movement disorders, particularly the anarthric NBIA group.

Analysis of a distinct speech disorder seen in chronic manganese toxicity following Ephedrone abuse.

INTRODUCTION: In the last fifteen years a new cause of chronic manganese toxicity has been recognized. It follows recreational intravenous injections of Ephedrone, synthesized from a cold remedies contained pseudoephedrine. Potassium permanganate is used as an oxidant. It presents with severe parkinsonism-dystonia and a characteristic dysarthria. OBJECTIVES: We performed a focus perceptual study of dysarthria in Ephedrone induced parkinsonism and compared the findings with the speech disorders seen in Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP). METHODS: A digital voice recording, perceptual speech analysis (Darley, 1975) [18], serial neurological assessment and Brain Magnetic Resonance (MR) imaging were performed at the Lviv regional Clinical Hospital. The results were analysed at the Institute of Neurology in London. RESULTS: Dysarthria developed after 8.5±3.2months of daily intravenous Ephedrone abuse and was an initial symptom in a third of cases. It was characterised by a robotic-flat prosody, whispering or continuous phonation, an inability to regulate pitch and volume, frozen lip articulation, a variable degree of dystonic tightness, difficulties in speech initiation and palladia, There was no nasality and swallowing was normal. In some patients speech deteriorated even after the discontinuation of Ephedrone. MR imaging, performed soon after drug cessation showed T1 signal hyperintesity in striatum and pallidum, especially in the Globus Pallidum interna. CONCLUSION: Ephedrone induced chronic manganese toxicity can lead to a mixed hypokinetic-dystonic dysarthria with a distinct dystonic pattern. Perceptual speech analysis can be a helpful ancillary investigation in the differential diagnosis of parkinsonism, and may permit the recognition of chronic manganese toxicity.

[Optimization of Antibiotic Prophylaxis in Minor Gynecologic Operations].

The aim of the study was to estimate the efficacy of various variants of antibiotic prophylaxis of infectious complications in female patients after histeroscopy. 109 patients were examined. The patients were hospitalized for planned historoscopy. 55 of them were treated prophylactically to prevent infectious complications with a broad spectrum antibiotic administered intravenously 30 min prior to the operation. A course antimicrobial therapy during the postoperative period was applied to 54 females. The results of the trial showed that single administration of an antimicrobial provided high level prevention of infectious complications, whereas the use of course antimicrobial therapy during the postoperative period was of no advantage by the efficacy.

A clinico-pathological study of subtypes in Parkinson's disease.

We have carried out a systematic review of the case files of 242 donors with pathologically verified Parkinson's disease at the Queen Square Brain Bank for Neurological Disorders in an attempt to corroborate the data-driven subtype classification proposed by Lewis and colleagues (Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 2005; 76: 343-8). Cases were segregated into earlier disease onset (25%), tremor dominant (31%), non-tremor dominant (36%) and rapid disease progression without dementia (8%) subgroups. We found a strong association between a non-tremor dominant disease pattern and cognitive disability. The earlier disease onset group had the longest duration to death, and greatest delay to the onset of falls and cognitive decline. Patients with a tremor dominant disease pattern did not live significantly longer than non-tremor dominant patients and showed no difference in mean time to onset of falls and hallucinations. Rapid disease progression was associated with older age, early depression and early midline motor symptoms, and in 70% of the cases, tremulous onset. The non-tremor dominant subgroup had a significantly higher mean pathological grading of cortical Lewy bodies than all other groupings (P < 0.05) and more cortical amyloid-beta plaque load and cerebral amyloid angiopathy than early disease onset and tremor dominant groups (P = 0.047). An analysis of cases with pathologically defined neocortical Lewy body disease confirmed the link between bradykinetic onset, cognitive decline and Lewy body deposition in the neocortex. Although neuropathological examination failed to distinguish the other subtypes, the classification scheme was supported by an analysis of clinical data that were independent of the basic subgroup definitions.

Patterns of levodopa response in Parkinson's disease: a clinico-pathological study.

Patients with Parkinson's disease who develop disabling levodopa-induced motor fluctuations have a stronger therapeutic response than those who experience a more modest but stable response. A difference in the histopathological lesion between the two groups might be responsible. Case records from 97 patients with pathologically proven Parkinson's disease were reviewed to determine the pattern of levodopa response. Pathological findings for fluctuating and non-fluctuating cases were compared. Patients with motor fluctuations had a younger age of onset and longer disease course (P < 0.001), although mean age at death was almost the same. Four milestones of advanced disease (frequent falls, visual hallucinations, cognitive disability and need for residential care) occurred at a similar time from death in each group; this interval was not proportionate to the disease duration. There were no significant differences in the severity or distribution of Lewy body or other pathologies. Irrespective of the pattern of levodopa response, patients reach a common pathological endpoint at a similar age, and the duration and manifestations of end-stage disease are alike. A non-linear or exponential time relationship may govern the late clinical and pathological progression of Parkinson's disease.

Implementation of the TMS in the early stages of Parkinson's disease.

47 PD patients were investigated with the single-pulse TMS to find out changes in motor evoked potential and motor conduction related to the stage of minimal motor symptoms and its further deterioration in groups with the different clinical types of the disease. The investigation revealed a markedly longer MEP duration along with the increased number of phases, than in controls, which were bilateral and advanced despite the minimal unilateral motor symptoms. There was also increased MEP amplitude in facilitation, with a higher degree of asymmetry, compared to controls. Patients with predominant rigid clinical forms had the further MEP duration and amplitude increase proportionally to bradikinesia and rigidity in the early stages of the disease. Patients with tremor predominant forms had no further changes in the MEP duration and amplitude, but had their motor CCT decreased in the early stages. Patients with the akinetic form were characterized by the asymmetric increase in the MEP Amplitude in relaxation and motor CCT shortening. Thus, TMS allows us to diagnose early the possible central motor changes secondary to Parkinson's disease, reveals the difference in compensational capacity according to the clinical type of the disease and helps in monitoring of the severity of motor changes in early stages.

[A differentiated approach to Parkinson's disease treatment in early stage of the disease]. / Differentsirovannyi podkhod k lecheniiu patsientov s bolezn'iu Parkinsona v rannem periode.

A conception of the approach to Parkinson's disease treatment at early stage, which could be realized in practice is suggested. The conception is based on the results of dopaminergic drugs treatment of 149 patients, aged 33-87 years. The patient's state was assessed by neurological examination and clinical scales with regard to different disease types, tremor and rigid, and levodopa doses--from moderate (up to 500 mg) to high (above 500 mg). A general treatment policy, including therapy directed to activation of regulatory and compensatory influences and differentiated usage of levodopa and combined therapy with levodopa and dopamine agonists, is presented.

[Clinical features of an early stage of Parkinson's disease]. / Klinicheskie osobennosti techeniia bolezni Parkinsona v rannem periode.

One hundred and forty-nine patients with Parkinson's disease (PD), mean age 66.3 years, have been examined. It was found that the early stage of the disease might include isolated depression, minimal movement disorders and functional compensation, the latter being observed during L-Dopa treatment. In general, the peculiarities of this stage comprise polymorphism of clinical symptoms, predominance of movement disorders over high mental dysfunctions and slow progression of pathological disorders with patient's adaptation to developing defect and reversibility of some dysfunctions under the treatment. The early stage was distinguished also by independence of high mental functions damage on movement disorders severity. More pronounced disturbances were detected in akinetic PD type in the presence of depression in the older patients. Depression may be a prodrome of movement disorders manifestation. The above peculiarities of the early stage are important for early PD diagnosis.

[Catecholamine metabolism in Parkinson's disease with depression]. / Obmen katekhomaminov pri bolezni Parkinsona s depressiei.

Daily urinary catecholamine excretion (DOPA, DA, DOPAC, NA, A) was studied in 66 patients with Parkinson's disease, 38 of them with differently expressed depression. Depression severity correlated with rigid form of disorders (p < 0.001). Biochemical profile of the depressive patients was characterized by noradrenaline (NA) to adrenaline (A) ratio reduction (p < 0.01) and dopamine to NA (p < 0.01) ratio increase on the background of total catecholamines deficit. Changes of NA/A and DOPA and correlation between DOPA and depression severity imply a role of dopamine neuromediator deficit in depression development.

[Catecholamine metabolism in different forms of Parkinson's disease]. / Obmen katekholaminov pri raznykh formakh bolezni Parkinsona.

Catecholamine metabolism was evaluated by daily urine excretion in patients with Parkinson's disease of tremor (18 patients) and rigid (14 patients) types. The group included 16 untreated patients. According to urine analysis, most informative peripheral markers for dopamine metabolism proved to be DOPA excretion, 3,4-dioxyphenylacidic acid (DOPAA) level and DOPA/DOPAA ratio. In the initial disease stage, a marked decrease of free dopamine and noradrenaline as well as dopamine metabolism intensification with corresponding DOPA/DOPAA ratio decrease were found. Significantly lower DOPAA and DOPA excretion was detected in patients with predominance of akinesia and rigidity types compared to tremor ones. In contrast to untreated patients, those treated with drugs containing dopamine revealed correlations between daily urine DOPA excretion as well as DOPA/DOPAA ratio with neurological symptoms severity.

Impaired production of plasma interleukin-6 in patients with Parkinson's disease.

The contents of interleukin-6 in the plasma from patients with Parkinson's disease and endogenous depression were compared by enzyme immunoassay. Interleukin-6 content in the plasma increased in the early stage of idiopathic parkinsonism complicated by depressive syndrome. A correlation was found between interleukin-6 content and changes in higher mental activity estimated by neuropsychological tests.

Clinical-neurophysiological features of motor lesions in patients with post-stroke epilepsy.

Twenty-two patients with post-stroke epilepsy (group 1) were studied, along with 30 stroke patients without epilepsy (group 2). Bilateral (on both the paralyzed and intact sides) decreases in the central conduction time (CCT) along the pyramidal tract were found in group 1, which were not seen in group 2, who had similarly severe motor lesions (p < 0.01). The tendency to decreased CCT was also seen 5-6 days after ischemic stroke in patients without epileptic manifestations, though CCT in this group increased by day 10-14; low values persisted in group 1 for prolonged periods. The facilitation differentiation (deltaF, the difference in CCT between resting and effort conditions) was also found to increase. In patients with post-stroke epilepsy, motor lesions were characterized by higher levels of muscle tone than in other stroke patients, though the levels of paralysis were similar.

[Disorders of muscle tonus and their treatment with sirdalud in patients in the early recovery period of ischemic stroke]. / Narusheniia myshechnogo tonusa i ikh lechenie sirdaludom u bol'nykh v rannem vosstanovitel'nom periode ishemicheskogo insul'ta.

The paper presents the results of clinical and neurophysiologic study of muscular tonus in 94 patients aged 42-70 years in early recovery after ischemic stroke. Selective role of spasticity was estimated in clinical pattern of motor disorders in groups of the patients with different disorders of muscular tonus with the same degree of paresis. Efficiency of antispastic preparation sirdalud was analyzed in 28 patients from this group. Sirdalud in daily dose of 6-12 mg in patients with prevalence of a spasticity in a clinical picture of the paresis and with either moderate or manifested degree of paresis of the extremities has significant antispastic effect without any decrease of muscular strength, which, in turn, increases the degree of restoration of motor functions.

[Clinical neuropsychological aspects of motor disorders in patients with post-CVA epilepsy]. / Kliniko-neirofiziologicheskie osobennosti dvigatel'nykh narushenii u bol'nykh s postinsul'tnoi épilepsiei.

The study included 22 patients with poststroke epilepsy (group 1) and 30 patients with stroke without epilepsy (group 2). A bilateral decrease of the time of central conduction (TCC) through pyramidal path (both on the paretic and intact side) was revealed in group 1. This was not observed in patients of group 2 with similar gravity of motor disorders (p < 0.01). Tendency to TCC decrease was also observed in patients without epileptic disorders by day 5-6 after ischemic stroke. However, TCC values were increased in such patients by day 10-14. Low indices persisted for a long time in patients with poststroke. There was also an increase of delta index of facilitation (the difference between TCC in rest and in muscle effort). It was also found that motor disorders in the group of patients with poststroke epilepsy were characterised by higher muscular tone than in poststroke patients with the same degree of the paresis.

[Epilepsy in patients with ischemic brain disease]. / Epilepsiia u bol'nykh s ishemicheskoi bolezn'iu golovnogo mozga.

The paper presents the results of follow-up study of 610 patients with ischemic stroke. In 52 patients (8.6%) there was observed symptomatic epilepsy conditioned by local causes (2 and more epileptic fits in anamnesis). The age of the onset of epileptic seizures was in the range 50-69 years, and men prevailed. From all 52 patients with episyndrome 36 had only one stroke, 16 patients-two and more strokes. 14 patients had fits before the stroke development. Meanwhile in 10 patients the fits were the first stroke symptoms (early) and in 28 individuals the fits arose 7 days after the stroke development (late). Significantly more severe disorders of dynamic praxis were revealed in psychologic examination of the patients with secondary generalized fits than of ones with partial seizures. Pathogenetic and clinical aspects of vascular epilepsy, interactions between transitory ischemic attacks and the fits which developed before the stroke are considered.

[The metabolic therapy of ischemic stroke: the use of nootropil]. / Metabolicheskaia terapiia ishemicheskogo insul'ta: primenenie nootropila.

54 patients were treated by notropil (pyracetam). The results of therapy were evaluated statistically according to a number of clinical scales and neurophysiologic indices (EEG and evoked potentials with mapping of bioelectric activity). The results were compared with the data about 56 patients of the control group which were treated by traditional method without application of notropil. Notropil was applied by two ways: small doses (4-12 g daily) during 5 days or high doses (10-12 g daily) during 30 days from the moment when the patient admitted to the hospital. Intravenous injections of the drug were used in all cases as well as its internal administration. It was showed either efficiency of the drug, especially in high doses, in early beginning of the treatment and its duration for at least 30 days or good tolerance of the drug. Authors supposed that application of pyracetam is not adequate in strokes with severe disorders of consciousness and cerebral edema.

[An analysis of the data from the neurophysiological examination of patients with bronchial asthma and hyperventilation]. / Analiz dannykh neirofiziologicheskogo obsledovaniia bol'nykh bronkhial'noi astmoi s giperventiliatsiei.

Bronchial asthma (BA) patients with hyperventilation (HV) were examined by means of evoked cutaneous sympathetic potential (ECSP) and short-latency evoked stem potentials to acoustic stimulation (SLESP to AS). Measurements of these parameters allowed quantitation and differentiation of hyperventilation disorders in BA patients. The latter were divided into 4 groups: BA patients with HV syndrome (HVS), BA patients with functional HV (FHV), BA patients with spontaneous HV (SHV) and BA patients without HV. BA patients with HVS exhibited a significant increase of latent ECSP period and latent periods III and V SLESP to AS peaks. This evidences for vegetative neuropathy and dysfunction of the pons and mesencephalic brain compartments. In BA patients with FHV there was a longer latent period II of SLESP to AS peak indicating dysfunction of caudal brain stem. BA patients with SHV and without HV had no significant shifts.

[The clinico-neurophysiological study of the effect of cerebrolysin on brain function in the acute and early recovery periods of hemispheric ischemic stroke]. / Kliniko-neirofiziologicheskoe issledovanie vliianiia tserebrolizina na funktsional'noe sostoianie golovnogo mozga v ostrom i rannem vosstanovitel'nom periodakh polusharnogo ishemicheskogo insul'ta.

Thirty patients with acute ischemic stroke and at early terms of postapoplectic recovery received cerebrolysin in daily doses 10, 20 and 30 ml for 5 days or 10 ml, i. v. for 10 days, respectively. The patients were examined for neurological status and cerebral function. In acute stroke the highest effect occurred in the affection of moderate severity. In severe stroke the drug stimulated recovery of impaired functions which tended to restore more quickly than in control subjects. In early convalescents cerebrolysin improved motor functions. Details of the results of the combined neurophysiological examination in the course of the treatment are discussed.

[The complex clinico-electrophysiological assessment of the motor disorders in patients in the early period of recovery from an ischemic stroke]. / Kompleksnaia élektrofiziologicheskaia otsenka dvigatel'nykh narushenii u bol'nykh v rannem vosstanovitel'nom periode ishemicheskogo insul'ta.

A neurophysiological analysis of motor affections has been made in post-apoplectic patients during early convalescence. Altogether 26 patients aged 45-68 were examined on week 3-4 since ischemic hemispheric apoplexy. Magnetic stimulation of cerebral cortex motor zones, measurements of M-response and evoked skin sympathetic potential. Mild or moderate motor dysfunctions were characterized by reduced amplitude of the M-response and prolonged central pyramid conduction on the affected side. Severe paresis is associated with no M-response to magnetic stimulation of the cortex on the affected side. Pathogenetic mechanisms of the above disorders and their implications for treatment and rehabilitation are discussed.

[A combined reflex method in the treatment of suppurative-infectious diseases in the postpartum period]. / Kompleksnyi reflektornyi metod lecheniia gnoino-septicheskikh zabolevanii poslerodovogo perioda.

The purpose of this study was to develop an effective pathogenetically validated method for the treatment of puerperants with pyoseptic diseases, making use of reflex therapy, and clinical assessment of this method. The study has involved 190 puerperants, in 50 of them the postpartum period ran a normal course and the rest 140 developed pyoseptic complications. Case histories were analyzed, clinical and laboratory tests (blood proteins, Mancini's test for immunoglobulins, Dorofeichuk's blood plasma lysozyme test) were carried out. Vegetative regulation was studied with the use of a vegetative test kit. A method for reflex therapy of the detected disorders of the vegetative regulation associated with puerperal pyoseptic diseases has been developed, resulting in strengthening of the defense potential of the body. Clinical assessment of the method has confirmed its high efficacy.