Characteristics of Tremor Induced by Lesions of the Cerebellum.

It is a clinical experience that acute lesions of the cerebellum induce pathological tremor, which tends to improve. However, quantitative characteristics, imaging correlates, and recovery of cerebellar tremor have not been systematically investigated. We studied the prevalence, quantitative parameters measured with biaxial accelerometry, and recovery of pathological tremor in 68 patients with lesions affecting the cerebellum. We also investigated the correlation between the occurrence and characteristics of tremor and lesion localization using 3D T1-weighted MRI images which were normalized and segmented according to a spatially unbiased atlas template for the cerebellum. Visual assessment detected pathological tremor in 19% while accelerometry in 47% of the patients. Tremor was present both in postural and intentional positions, but never at rest. Two types of pathological tremor were distinguished: (1) low-frequency tremor in 36.76% of patients (center frequency 2.66 ± 1.17 Hz) and (2) normal frequency-high-intensity tremor in 10.29% (center frequency 8.79 ± 1.43 Hz). The size of the lesion did not correlate with the presence or severity of tremor. Involvement of the anterior lobe and lobule VI was related to high tremor intensity. In all followed up patients with acute cerebellar ischemia, the tremor completely recovered within 8 weeks. Our results indicate that cerebellar lesions might induce pathological postural and intentional tremor of 2-3 Hz frequency. Due to its low frequency and low amplitude, quantitative tremorometry is neccessary to properly identify it. There is no tight correlation between lesion localization and quantitative characteristics of cerebellar tremor.

[Pulvinar]. / Pulvinar.

The pulvinar is the largest nucleus of the thalamus. Its lateral and inferior areas have rich connections with the visual- and dorsolateral parietal cortices. Several cells in the medial and upper area connect the anterior cingulum and the premotor and prefrontal association areas. This neuronal network was considered to organize the saccades and visual attention. Other cells in the medial nucleus have axonal connections with paralimbic-, insular and higher order association-cortices. The medial structure integrates complex sensory information with limbic reactivity settings, transmitting these to the temporal and parieto-occipital centres. The pulvinar is supplied by the posterior chorioideal artery. Visual salience is considered to be an important function of the pulvinar. Visual selection enables subjects to choose the actually adequate behavioral act. To serve the visual salience the pulvinar may also inhibit inappropriate eye movements. The pulvinar appears to be a key structure of the EEG's alpha rhythm generator, acting together with the parietooccipital and temporal cortices. Dynamic fluctuation of BOLD signals on fMRI correlates well with the change of alpha power even in resting state. We presume that the pulvinar is part of a closed cortico-subcortical circuit, analogous with the striatum, but the output of the pulvinar initiates complex behavioral reactions, including perception, selective attention and emotions. Damage of the pulvinar may elicit contralateral visual neglect, because of the dissociation of the neuronal network integrated by the superior temporal area. Increased activity of the pulvinar was found during abrupt reaction to fearful visual signals; and also in the etiopathology of endogenous depressions through the alteration of serotonin transporters. Increased bilateral signal intensity of the pulvinar on MRI was detected in cases of the new variants of Creutzfeldt-Jakob- and Fabry diseases.

[Neurophobia]. / Neurofóbia.

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 clinical competence. 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 the neurosciences seems to be associated with insensitivity to human-centered culture and with the corruption of empathic thinking. The professional burnout of medical doctors and students can be explained by stress, loss of respect, permanent competition, independence that interferes with responsibility, stiff hierarchy of the medical establishment, fear of diagnostic failures and of economical difficulties. The scores of depression were higher in female students than in males. The idea of the "good neurologist" has been changed. Business-oriented care, shortage of time, and financial restrictions corroded conventional practice and ceased vocational idealism. At present, personal teaching is being transformed into impersonal multimedia instruction and learning. Because of the drastic change of values, the age of inner-oriented professionals has ended also in medicine. Medical doctors follow even less the traditional path of professional behavior, but according to social demands, they choose their specialization for financial reasons. 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 neuroanatomy and neurophysiology, 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 needed whom neurology residents would have to meet personally with optimal frequency. However, these requirements seem to fail because of the chiefly technical character of the actual reforms.

120 years of hippocampal Schaffer collaterals.

Károly Schaffer (1864-1939) was a Hungarian neurologist who distinguished himself through original discoveries in human neuropathology. At the beginning of his scientific carrier, he described the cellular and fiber structure of the hippocampus, earning him a high reputation in neuroscience. Schaffer (1892) described the so-called "collateral fiber system" that connects the CA3 and CA1 regions of the hippocampus, known today as Schaffer collaterals. To decipher the history of this well-known eponym, we review Schaffer's original German publication and follow the impact of his research in the contemporary literature.

[EEG investigations in cognitive impairments]. / Kognitív zavarok vizsgálata EEG-vel.

The EEG is an indicator of all physiological and neuropsychological activity. The alpha rhythm was considered as a key phenomenon in research of human mentation from the discovery of EEG. Two methods are known for the estimation of cognitive deficit by the use of quantitative EEG (QEEG). The first is based on the hypothesis, that the mean values of the normal EEG from healthy volunteers can be used as reference, and deviation from the normal values of EEG parameters may suggest disease. This kind of "neurometry" was elaborated by R. E. John. The second method assesses event related (ER) transients evoked by somatosensory and mental stimuli. Quantity and localization of signals may refer to the functional state of the cortex. These reactions depend strongly on the test-paradigms. Recognition of the attention-intention cycle disclosed the physiological mechanism of ERD (event related desynchronisation) and ERS (event related synchronisation). In contrast with the classical "stimulus-reaction" model, both perception and voluntary movement are initiated by the brain itself, and not by the environment. Human behavior and conscious actions depend on the intention. QEEG analysis proved that the attention and intention localize in segregate areas of the brain. Both "static" and "dynamic" neurometric methods are able to differentiate the EEG records of demented patients from healthy controls, furthermore some dementias from each other. We conclude that with the help of sophisticated methods of QEEG analysis minimal functional deficit of the electrogenesis can be recognized, which could be helpful in the differential diagnosis Notwithstanding the EEG can not explain the evolution neither the normal or the diseased mental processes. The only "instrument" which is able to approach the human mind is the human cogitation itself with the aids of appropriate tests. The QEEG can be conclusive in the analysis of particular processes of mental activity, such as timing, state of activation, hierarchical organisation of cortical territories and mechanism of electrogenesis.

[Ulcerative carpal tunnel syndrome]. / Trophicus fekélyt okozó carpalis alagút szindróma.

The carpal tunnel syndrome is the most frequent compression-induced neuropathy. A severe but rare clinical manifestation of this disorder associates with ulceration, acral osteolysis and mutilation of the terminal phalanges of the second and third fingers. Recognition of this disorder is difficult, because various dermatological and internal diseases might lead to acral ulcerative lesions, and these patients are seldom referred to neurological and/or electrodiagnostic examination. In this article, we present three cases of this rare clinical form of carpal tunnel syndrome and discuss the electrodiagnostic findings. The early diagnosis is important since decompression of the median nerve in due time might prevent mutilation and could significantly improve the patients' quality of life.

[Vascular or "lower body Parkinsonism": rise and fall of a diagnosis]. / Vascularis vagy "lower body Parkinsonizmus". Egy diagnózis tündöklése és Bukása.

UNLABELLED: The "arteriosclerotic parkinsonism", which is called vascular parkinsonism (VP), was first described by Critchley'. The broad based slow gait, reduced stride lenght, start hesitation, freezing and paratonia was mentioned as "lower body parkinsonism" (LBP) which can be associated by slow speech, dysexecutive syndrome, and hand tremor of predominantly postural character. In VP the DAT-scan proved normal dopamine content of the striatum in contrast with Parkinson's disease (PD). Additionally, Lewy bodies of brainstem type were not found in VR Probability of VP increases if central type pathologic gait is prominent; the hands are slightly involved, the MRI indicates transparent periventricular white substance and/or brain atrophy. In some cases differentiation of gait apraxia and parkinsonism could be challenging. There is no rigor of the lower limbs at rest in neither of them, the disturbance of movement is evoked by the gait itself. Three subtypes of "gait ignition failure" has been recently described: (1) ignition apraxia, (2) equilibrium apraxia and (3) mixed gait apraxia. The primary progressive freesing gait was considered as a Parkinson-plus syndrome. Freesing occurs more frequently in diseases with pakinsonism than in PD. The grade of ventricle dilatation and the frontal leukoaraiosis was similar in LBP and gait apraxia. In cases of normal pressure hydrocephalus the impaired gait may mimic PD. Pathologic gait in VP can be explained by the lesions of the senso-motor association pathways in dorsal paramedian white substance within the vulnerable borderzone region. These may be colocalized with the representation of the lower extremities in the posterior third of the supplementer motor area. Rektor2 proposed to change the name of LBP to "cerebrovascular gait disorder". Notwithstandig central type gait disorder develops also in many degenerative diseases other than cerebro-vascular origin. The neuronal net controling the regulation of movement is widespread, therefore several cortical and subcortical lesions could elicit large variations of pathologic gait, ie.: ataxia, apraxia, ignition failure, akinesis etc. IN CONCLUSION: most of the central gait disorders regarding the pathology and their appearance can not be called "parkinsonism"; these are much closer related to the localization of lesions rather than to the diagnostic categories.

[Neurology! Adieau? (Part 1)]. / Neurológia! Adieau? 1. Rész.

The neurological practice suffered considerable changes during the last twenty years. The recent therapeutic methods and the acceptance of the ideology of evidence based medicine, which is based on confidence in statistics, changed the reasoning of the neurologists. Therapy protocols intrude into the field of individual medicine, and doctors accept treatment schemes to alleviate responsibility of their decisions. In contrast with this, recent achievements in pharmacogenetics emphasize the importance of individual drug therapies. The protocol of intravenous cerebral thrombolysis does not require defining the origin of cerebral ischaemia in the acute stage, therefore, this procedure can be regarded as human experiment. According to the strict protocol thrombolysis might be indicated only in 1-8% of patients with cerebral ischaemia. According to the Cohrane database more trials are needed to clarify which patients are most likely to benefit from treatment. Because of the change in therapeutic principles transient ischaemic attack has been newly defined as "acute neurovascular syndrome". Multiplication of neurological subspecialties has been facilitated by the development of diagnostic tools and the discovery of effective new drugs. The specialization led to narrowing of interest and competency of clinicians. Several new neurological scientific societies were founded for the representation of specific disorders. In Hungary, between 1993 and 2000 nine scientific societies were grounded within the field of clinical neurology. These societies should be thankful to the pharmaceutical industries for their existence. In some European countries in 2007 only three neurological subspecialties were accepted, which are neurophysiology, neuro-rehabilitation and child-neurology. Neuro-radiology is in the hands of general radiologists, the specialization is not granted for neurologists. Because of the subspecialization the general professionalism of neurologists has diminished. Among young neurologists the propedeutic skills suffered most seriously. Subspecialisation of teachers also interferes with the practice oriented teaching of medical students and residents.

[Neurology! Adieau? (Part 2)]. / Neurológia! Adieau? 2. Rész.

The education of neurologists is debilitated worldwide. University professors are engaged in teaching, research and patient-care. This triple challenge is very demanding, and results in permanent insecurity of University employees. To compensate for the insufficient clinical training, some institutes in the USA employ academic staff members exclusively for teaching. The formation of new subspecialties hinders the education and training of general neurologists. At present, four generations of medical doctors are working together in hospitals. The two older generations educate the younger neurologists who have been brought up in the world of limitless network of sterile information. Therefore their manual skills at the bedside and their knowledge of emergency treatment are deficient. Demographics of medical doctors changed drastically. Twice as many women are working in neurology and psychiatry than men. Integrity of neurology is threatened by: (1) Separation of the cerebrovascular diseases from general neurology. Development of "stroke units" was facilitated by the better reimbursement for treatment and by the interest of the pharmaceutical companies. Healthcare politics promoted the split of neurology into two parts. The independent status of "stroke departments" will reduce the rest of clinical neurology to outpatient service. (2) The main argumentation to segregate the rare neurological diseases was that their research will provide benefit for the diseases with high prevalence. This argumentation serves territorial ambitions. The separation of rare diseases interferes with the teaching of differential diagnostics in neurological training. The traditional pragmatic neurology can not be retrieved. The faculty of neurology could retain its integrity by the improvement of diagnostic methods and the ever more effective drugs. Nevertheless, even the progression of neurological sciences induces dissociation of clinical neurology. Neurology shall suffer fragmentation if the professional authorities fail to control the separation of subspecialties, if teaching of future neurologists, including practical knowledge and skills of diagnostic decision making, is not supported.

How does the brain create rhythms?

Connection was found between rhythmic cortical activity and motor control. The 10 Hz micro-rhythm and the 20-30 Hz bursts represent two functional states of the somatomotor system. A correspondence of the central micro-rhythm of the motor cortex and the physiological hand tremor (8-12 Hz) is presumed. The precise tuning of the motor system can be estimated by the frequency of repetitive finger movements. In complex tapping exercise, the index finger is the most skillful, the 3rd, 4th and 5th fingers keep rhythm with less precision. It was found that the organization of mirror movements depends on the cortical representation of fingers. Mirror finger movements are more regular if the subject begins the motor action with the 5th (small) finger. Concerning cortical regulation of finger movements, it was suggested that there are two time-keeping systems in the brain; one with a sensitivity above and another with a sensitivity below the critical frequency of 3 Hz. The preferred meter which helps to maintain synchronous finger movements is the cadence of 4/4 and 8/8. We observed that the unlearned inward-outward sequential finger movement was equally impaired in nonmusician controls and patients with Parkinson-disease. In movement disorders, the ability of movement and the "clock-mechanism" are equally involved. The polyrhythmic finger movement is not our inborn ability, it has to be learned. The "timer" function, which regulates the rhythmic movement, is presumably localised in the basal ganglia or in the cerebellum. The meter of the music is built on the reciprocal values of 2 raised to the second to fifth power (1/1(2), 1/2(2), 1/2(3), 1/2(4), 1/2(5)). The EEG frequencies that we consider important in the regulation of conscious motor actions are approximately in the same domain (4, 8, 16, 32, 64 Hz). During music performance, an important neural process is the coupling of distant brain areas. Concerning melody, the musical taste of Europeans is octave-based. Musical ornaments also follow the rule of the gothic construction, that is: pursuit of harmony towards the single one rising from the unification of 8-4-2 classes. Leibnitz concerned music as the unconscious mathematics of the soul. Movement-initiating effect of music is used in rehabilitation of patients with movement disorders. The meter and rhythm have superiority over the melody. It is possible that rhythmic movements can be generated also in the absence of sensory input and the central oscillators can produce "fictive motor patterns".

Quantitative analysis of motor performance in epilepsy patients treated with valproate.

PURPOSE: The aim of our study was to detect objective signs of deterioration of motor performance in epilepsy patients treated with chronic valproate therapy. METHODS: We examined 14 controls and 15 epilepsy patients receiving chronic valproate monotherapy, who had no subjective complaints related to motor function. Regularity and maximum frequency of repetitive hand and finger movements, and simple reaction time were measured. Intensity and frequency characteristics of resting and postural tremor were assessed using accelerometry. Data were statistically evaluated. RESULTS: Repetitive hand and finger movements were significantly more irregular and the maximum frequency of repetitive movements was significantly lower in the valproate group than in controls. Resting tremor peak frequency and motor reaction time of the two cohorts did not differ. CONCLUSIONS: This is the first study, which quantitatively assesses motor performance of patients with epilepsy on chronic valproate therapy. The results suggest significant irregularity of repetitive hand movements and finger tapping even in patients with no motor complaints. Objective methods might help to recognize valproate-induced motor performance deterioration.

Levetiracetam reduces myoclonus in corticobasal degeneration: report of two cases.

Levetiracetam (LEV) has been shown to suppress myoclonus of various origins. Corticobasal degeneration (CBD), a progressive neurodegenerative disorder with Parkinsonian syndrome, is frequently accompanied by myoclonus. We investigated the effect of LEV on myoclonus in two CBD patients. LEV remarkably decreased the myoclonic activity in both patients already at 1,500 mg/day dose. This is the first report on LEV alleviating myoclonus in CBD. Our data indicate that it might be worthwhile to assess this effect in an appropriately designed study.

Hypocapnia induced by involuntary hyperventilation during mental arithmetic reduces cerebral blood flow velocity.

Functional neuroimaging studies have shown that cognitive processes increase regional cerebral blood flow in relation with enhanced neuronal activity. However, cognition induces elevation of blood pressure, heart rate and respiratory rate, each of which also affects cerebral circulation. For proper interpretation of functional neuroimaging data, it is necessary to dissociate the effects of systemic and local metabolic reactions on regional cerebral circulation. To elucidate this interaction, we examined the changes in cerebral blood flow velocity, which were caused by voluntary hyperventilation-induced hypocapnia without cognitive effort and hypocapnia evolving during mental arithmetic task. The cerebral blood flow velocity was recorded in the middle cerebral arteries, using transcranial Doppler sonography. Respiratory rate, end-tidal partial pressure of CO(2), heart rate and arterial blood pressure were simultaneously monitored. Data were statistically evaluated. Hypocapnia induced by voluntary hyperventilation without cognition decreased the cerebral blood flow velocity. During mental arithmetic, the cerebral blood flow velocity first increased, but the hypocapnia, which was induced by involuntary hyperventilation related to cognitive effort, reduced it. This implies temporary vasoconstriction of cerebral microvessels, and the increase in cerebral vascular resistance index supports this finding. These results suggest that hypocapnia, which develops during cognition, may decrease blood flow velocity in the middle cerebral arteries, which interferes with the neuronal activity-driven regulation of cerebral circulation. In conclusion, when interpreting the results of functional neuroimaging studies on cognitive mechanisms, the tight coupling of the effects of mental processes and autonomic/metabolic reactions should be considered.

Post-movement beta synchronisation after complex prosaccade task.

OBJECTIVE: Post-movement beta synchronisation (PMBS) has been described as an induced, localised increase of beta activity over the contralateral sensorimotor cortex after termination of voluntary limb movement. The aim of our study was to investigate whether ocular saccades also evoke movement related EEG changes. METHODS: Complex saccades were recorded in six healthy volunteers using electro-oculography. EEG power changes in the beta frequency band were measured before, during and after saccades. RESULTS: Significant increase of beta-power was observed over the frontocentral region of both hemispheres after the offset of the complex saccade task. The latency of ocular PMBS was about 1100ms. CONCLUSIONS: Ocular PMBS evoked by complex saccade task is similar to that of recorded after limb movements. Its presence over both hemispheres irrespective of the direction of saccades indicates bilateral activation of cortical areas connected with the execution and planning of ocular movements. SIGNIFICANCE: The present paper is the first report on eye-movement related post-movement beta synchronisation. Investigation of ocular PMBS can be used both for research and clinical purposes for the functional assessment of neuronal networks controlling eye movements.

[Intracerebral steal after acetazolamide administration]. / Intracerebralis steal jelenség acetazolamidterhelés alatt.

Occlusion or high grade stenosis of the internal carotid artery may be asymptomatic depending on the collateral patterns in the circle of Willis and the reserve capacity of the microvascular (arteriolar) system. The distensibility of the cerebral arterioles may be described quantitatively by the vasomotor reactivity. We present three patients with severe stenosis of an internal carotid artery associated with more severe stenosis or occlusion of the contralateral internal carotid artery. We continuously measured blood flow velocity in both middle cerebral arteries by transcranial Doppler ultrasound in rest and for 20 minutes after IV administration of 1 g acetazolamide. Arterial blood pressure was determined with tonometry, end-tidal CO2 was determined by a capnometer. In resting condition the anterior communicating artery, the posterior communicating artery and the ophthalmic artery supplied collateral blood flow towards the side of the more severe internal carotid artery disease. Blood flow velocity decreased after acetazolamide administration in all patients in the middle cerebral arteries on the side of the more severe occlusive carotid disease, while increased on the contralateral side. We assume that the exhausted arteriolar system on the more severely affected side was not able to further dilate and the open collateral system could have driven blood towards the other side with preserved reserve capacity. The reduced blood flow velocity in the middle cerebral arteries after acetazolamide may reflect this intracerebral steal phenomenon.

[Neurology of cognition and language in the publications of Kálmán Sántha and today]. / A gondolkodás és a beszéd neurológiája Sántha Kálmán közleményeiben és ma.

Based on histopathological investigation of the brain of exceptionally talented persons Sántha found increased volume of parietal association areas with abundance of cells. He supposed that the angular gyrus may be a "memory field". In his publication Genius and inheritance he expressed that: "Talent is a child of the present, but the genius is born for eternity." He discussed the localization of sensory and motor amnestic aphasia analysing the signs of patient with brain tumor and called attention to concomitant psychological symptoms. He found crossed aphasia in twice as many lefthanded than righthanded persons. This may explain the recent observations that the restitution of aphasia is predetermined; speech ability of ambidexterous or latent lefthanded persons improve better. He analysed the topography of emotional and voluntary facial palsy. The currently accepted hierarchical concept of mental and speech ability can be derived from the ouevre of Sántha and his predecessors. Sántha can be honoured as a forerunner of the modern theories of aphasia localization.

Simultaneous central and peripheral nervous system involvement in systemic lupus erythematosus.

Systemic lupus erythematosus is a frequent autoimmune disease, affecting several organs, including the brain, spinal cord and nerves. Cerebral vasculitis, transverse myelitis and polyneuropathy are the most common neurological manifestations. We report a case of a 46 years old woman who suffered incomplete transverse myelitis at the age of 44. After 2 years the second relapse presented with arthralgias, painful paraesthesias and weakness of the lower limbs. Neurological signs suggested involvement of the central and the peripheral nervous system. Based upon clinical and laboratory findings systemic lupus erythematosus was diagnosed. Magnetic resonance imaging revealed two hyperintense lesions on T2 weighted scans within the cervical spinal cord. The brain scan was normal. Protein content was slightly elevated in the cerebrospinal fluid, with normal cell count. Electrophysiological examinations diagnosed a subacute sensory-motor axonal polyneuropathy. On methylprednisolone treatment her condition improved. Simultaneous development of central and peripheral lesions of the nervous system in cases with systemic lupus erythematosus may lead to a challenge to establish the diagnosis.

One-and-a-half syndrome--two cases.

One-and-a-half syndrome is characterized by combination of the clinical features of unilateral horizontal gaze palsy and internuclear ophthalmoplegia. The common symptoms are double vision and oscillopsia. The lesion is located in the paramedian pontine reticular formation, involving the centre of horizontal gaze and medial longitudinal fasciculus. More extensive brainstem damage may result in additional neurological signs. The most frequent underlying diseases are vascular insults, multiple sclerosis, and brainstem tumor. We present two cases of one-and-a-half syndrome. Both patients had lacunar infarction in the paramedian pontine tegmentum, revealed by MRI. The first patient had isolated eye movement disorder, while the second had additional nuclear-type facial paresis. In the first case brainstem evoked potentials indicated brainstem damage, in the second patient it was normal. Ocular symptoms improved within some days in both patients.