The European Federation of Neurological Societies (EFNS) Scientific Panel on Neurorehabilitation established a Task Force on standards in neurological rehabilitation in June 1996. The remit for the Task Force was to: (1) produce a report on the state of neurological rehabilitation across Europe; and (2) recommend standards for the provision of neurological services for disabled people. The main conclusions of the Task Force were as follows:
To assess the effect of tolcapone added to levodopa plus benserazide or carbidopa on the “wearing‐off” phenomenon in patients with Parkinson's disease, we undertook a double‐blind, randomized, placebo‐controlled, parallel‐group study of tolcapone 50, 200, or 400 mg three times daily (t.i.d.) for 6 weeks in addition to levodopa therapy. We studied 154 parkinsonian patients, aged 40 years or more, who presented with the “wearing‐off” phenomenon despite “optimal” antiparkinsonian therapy. The main outcome measures were “on”‐ and “off”‐time, Investigator's Global Assessments, Subscales of the Unified Parkinson's Disease Rating Scale, changes in levodopa dosage, and safety and tolerability. Tolcapone was more effective than placebo in reducing the “wearing‐off” phenomenon between baseline and week 6 at all three dosages. Tolcapone 200 mg t.i.d. increased “on”‐time from 37.9% of the waking day to 50.8% ( < 0.01) and reduced “off”‐time from 26.7% of the waking day to 16.4% ( < 0.05). Tolcapone treatment was generally well tolerated at all dosages. Initial exacerbation of adverse dopaminergic effects was controlled by levodopa dosage adjustment; at week 6, the mean total daily levodopa dosage had decreased by 80 mg, from 694 mg at baseline, in the tolcapone 200 mg t.i.d. group ( < 0.01). We conclude that the addition of tolcapone to levodopa plus a decarboxylase inhibitor effectively and safely reduces the “wearing‐off” phenomenon in parkinsonian patients.
Hypermetabolism, which can lead to wasting syndrome, is well recognized in diseases such as AIDS, cancer, rheumatoid arthritis, sepsis and burns. In these conditions proinflammatory cytokines are thought to be essentially involved. In experimental allergic encephalitis (EAE), which is regarded as an animal model of multiple sclerosis (MS), wasting syndrome and elevated levels of cytokines have also been reported. The aim of this study was to investigate whether hypermetabolism does occur in MS patients. After a 3‐day standard diet the basal metabolic rate (BMR) was measured by indirect calorimetry in 20 MS patients and 10 healthy controls. Body composition was assessed using an impedance analyser and lean body mass (LBM) was calculated. Other metabolic disturbances and infectious disease were ruled out by clinical examination and various laboratory tests. Tested by analysis of variance (ANOVA), the BMR corrected for LBM was increased by an average of 6% in the patients group ( < 0.05) as compared to the controls. As far as we know this is the first study demonstrating the presence of hypermetabolism in MS.
Many electrophysiological tests have been used to determine prognosis and extent of recovery in Bell's palsy but the reliability and sensitivity of the different parameters used is still controversial. We performed bilateral percutaneous facial nerve conduction studies, and volitional needle electromyography on 23 patients within 10–14 days post onset of their Bell's palsy. The following parameters were assessed: denervation and recruitment of the frontalis and orbicularis oris muscles, latency of the compound muscle action potential (CMAP), and CMAP amplitude ratio. The patients were re‐examined 6 months later and their recovery graded according to the House‐Brackman classification. The CMAP amplitude ratio and the recruitment scores of the frontalis and orbicularis oris muscles were the only parameters to reliably predict outcome ( = 0.016, 0.007 and 0.036, respectively). All patients with a CMAP amplitude ratio above 10% had a complete recovery. Since Bell's palsy is probably caused by herpes simplex virus, the active disease process is completed within 10–14 days; therefore, facial nerve conduction studies and electromyography at that time are appropriate to predict prognosis.
Twenty‐six patients with episodic cluster headache were subjected to pupillometric examinations of the responses to bilateral conjunctival instillations of a single drop of a 1% phenylephrine and a 2% tyramine hydrochloride solution. Five patients had a Horner‐like syndrome on the symptomatic side, where they exhibited an increased pupillary response to phenylephrine and a decreased response to tyramine, i.e. a pattern compatible with postganglionic sympathetic dysfunction. It is suggested that these patients constitute a subgroup among the patients with cluster headache. The pupillary response to phenylephrine was frequently increased on the symptomatic side, while that to tyramine was reduced. This may indicate dysfunction of the sympathetic postganglionic fibers to the iris (and tentatively to the cephalic vasculature). Such an interpretation may be supported by the finding that a marked mydriatic response on the symptomatic side to tyramine was associated with an inactive cluster headache, frequently over many years.
We studied the occurrence of sleep related breathing disturbances (SRBD) and nocturnal akinesia in patients with Parkinson's Disease (PD) and evaluated the likelihood that PD symptoms consistently influence these sleep disorders. Ninety‐two PD patients (mean age 69 years; mean Webster rating score 13) were studied. An ambulatory sleep disorder screening device (MESAM4) was used to measure oxygen saturation, heart rate, snoring sounds and body position during sleep. Sleep related breathing disturbance (SRBD) was diagnosed if typical cyclic oxygen desaturations > 4% more than 10 times/h were recorded. A nocturnal akinesia was diagnosed if there were < 0.3 changes of body positions/hour or a maximal time in one position of more than 4.3 h. There was evidence of SRBD in 17% of PD patients. SRBD correlated positively with high rigidity and bradykinesia scores as well as high Webster rating scale scores and age of men. Thirty percent of PD patients had an objective nocturnal akinesia. This was also combined with a high rigidity score. No relation between SRBD or Nocturnal akinesia, ‐Dopa intake, duration of the disease or onset of the disease was found.
To better understand “la marche à petits pas”, we focused on ground reactions forces, a key interface between muscular activity and gait kinematics. Computerized recordings were used to measure kinematic and kinetic variables in 11 patients aged between 65 and 84 years and 13 control subjects aged between 65 and 86 years. Kinematics was studied with an ELITE 3D motion analysis system. Anteroposterior and vertical reaction forces were measured under each foot with three force platforms. Free gait and gait with comparable stride lengths in the patients and the control subjects were analysed. Patients displayed higher vertical displacements of toes, ankle, and knee during gait and difficulty in initiating and maintaining rhythmic stepping. In patients, the amplitude and direction of anteroposterior forces were impaired under the starting foot and under both feet during gait. Their vertical forces were weaker and less symmetrical than in control subjects at the start and while walking. Short stride lengths, high vertical foot displacements and laborious rhythm installation seem to be due to perturbations observed in amplitude and regularity of the time course in both vertical and anteroposterior ground reaction forces.
In the period 1984–1993, we carried out an incidence and prevalence study of motor neuron disease in Coastal and Mountainous Regions, Croatia. This was the first epidemiological study on motor neuron disease in Croatia. A total of 22 incident cases were identified. The crude annual incidence rate was 0.68 (95% confidence interval 0.43‐1.03) per 100,000 person‐years; 0.95 (95% confidence interval 0.60‐1.43) per 100,000 person‐years for men and 0.42 (95% confidence interval 0.26‐0.63) per 100,000 person‐years for women. The rate adjusted to the European population was 0.63 (95% confidence interval 0.39‐0.95) per 100,000 person‐years. The age‐adjusted incidence in our population is similar to the rates, standardized to the European population, observed in Italy, but lower than recent rates in the US and northern European studies. On 31st December 1993, there were 18 prevalent cases. The prevalence adjusted to the European population was 5.24 (95% confidence interval 3.10‐8.28) per 100,000 population.
Normal subjects and right‐ and left‐brain‐damaged patients with and without neglect performed a task of immediate visual memory and a task of same‐different judgment on visual items. In both tasks, stimull consisted in geometrical patterns, which differed either on the right or on the left side. Only right‐brain‐damaged patients with neglect showed an impaired performance in these tasks. They performed worse on items differing on the left side than on items differing on the right side. This impairment was more severe on the memory task than on the same‐different task, suggesting that a lateralized visual memory deficit contributes to the behavioural manifestations of left hemineglect.
Data from 112 patients with severe, refractory, partial epilepsy, who were treated with adjunct vigabatrin, were used to compare the cost‐of‐care for patients who responded to the therapy and those who did not. For patients who responded to vigabatrin, the direct and indirect costs were lower than the costs for patients who did not respond to treatment. The major impact on direct costs was a 69% and 59% decrease in rate of hospitalization and length of stay in hospital, respectively, for the responder group. This decrease in costs outweighed the additional drug costs associated with continued vigabatrin therapy.
Lead‐poisoning is a disease of environmental origin. The primary target for lead is the nervous system. Lead ions are able to accelerate lipid peroxidation (LP) and, hence, induce cellular damage. Endothelial cell alteration and cerebral microvessel dysfunction are important in lead‐induced encephalopathy. It is possibile that the altered functional state of brain microvasculature cannot ensure the adequate level of local cerebral blood flow (LCBF). The purpose of the present study was to evaluate LP in brain tissue homogenates of the cerebral cortex (CTX) and hypothalamus (HYP) of 15 lead‐exposed vs seven control rabbits after a short‐time lead exposure (5 and 10 days, 40 mg/kg). Another aim was to compare the dynamics of changes in LP and LCBF, detected by the H clearance method in another group (seven lead‐exposed rabbits vs seven controls). The basal level of thiobarbituric acid reactive substances (TBARS), the Fe‐stimulated part of the TBARS (Fe‐TBARS) and diene conjugates (DC) were used for the evaluation of LP in the brain tissue. A tendency to the slight enhancement of TBARS and DC concentrations in brain homogenates 5 days after the 10 days lead exposure period was found (CTX < 0.05). The enhancement of the Fe TBARS was expressed maximally on 1 day after 10 day exposure period (CTX < 0.05, HYP < 0.001 compared to controls). The biphasic reaction of changes in LCBF was detected: during (5th day) and in 1 day after a 10 day exposure period a decrease of LCBF in both investigated regions was found (10.5 and 9.3 ml/100g/min i.e. 28.6 and 24.1%, respectively, in CTX, < 0.05; and 11.2 and 10.1 ml/100g/min i.e. 19.9 and 18.7%, respectively in HYP, < 0.05); on the 5th day after exposure minimal tendency to increase was found (7.1 ml/100g/min, < 0.01 in HYP compared with controls). In conclusion, lead induces excessive LP in brain homogenates and disturbances in LCBF. However, the causal relationship between those events remains to be proven.
Capsaicin (50 mg/kg s.c./25 μl) was administered to rats on the 2nd and 5th days after birth. The animals were raised, and from the age of 3 months the properties of the evoked activity were tested in the contralateral barrelfield. This neonatal capsaicin treatment was found to induce profound changes in the responsiveness of the barrel cortex in the adult rats: (1) the receptive field of the neurons in the Cl barrel was expanded; units within a particular barrel were driven by a significantly larger number of vibrissae than in the controls. (2) The rate of discharge evoked by the related vibrissa deflection was enhanced, while (3) the angular sensitivity of the neurons was decreased. (4) The most prominent change in cortical activity was observed by autoradiography: capsaicin‐treated rats exhibited an enhanced labelling of different types of neurons throughout the hemisphere (surpassing the cortical representation of stimulated vibrissae). The present observations indicate that neonatal capsaicin affects the functional activity of the rat somatosensory cortex. It is suggested that unmyelinated sensory afferents play a role in the development of the rat somatosensory system.
We describe the case of a 42‐year‐old woman who had two episodes of visual loss, first in one and later in the other eye, which caused bilateral reduction of visual acuity to 2/10 with optic atrophy. Detailed clinical and laboratory assessment revealed an activated protein C (APC) resistance and no other obvious cause. APC resistance has not been previously reported as an etiologic factor of central retinal artery occlusion.
We present the coagulation and serological studies of four patients with Sneddon's syndrome, in which antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant) were determined using cardiolipin and a mixture of phospholipid from rabbit brain as antigen for detection of lupus anticoagulant by ELISA. Our results support a relation between Sneddon's syndrome and lupus anticoagulant (IgG subtype) in all cases. The anticardiolipin antibody test was positive only in two cases (one in low level). All patients could be diagnosed as having primary antiphospholipid antibody syndrome. Antiaggregant treatment was not effective in preventing thrombosis in two cases. Three of four patients received long‐term oral anticoagulation therapy, with no recurrence of thrombosis observed for a period of at least 3 years.
A 19‐year‐old man with a history of adrenal insufficiency and epilepsy for several years presented with headache, obtundation, status epilepticus and papilloedema. A computed tomography‐scan was consistent with a fronto‐collosal glioma. However, this patient's condition spontaneously improved after a brain biopsy. Therefore, the diagnosis of adrenoleukodystrophy (ALD) was established, based on histological findings, positive family history and plasma fatty acid analysis. In ALD, an acute and reversible worsening of brain demyelination with increased intracranial pressure may be evocative of a cerebral neoplasm.
Three patients with thymoma associated myasthenia gravis complicated by the nephrotic syndrome are described. There were two male and one female patients with a mean age at presentation of 55.6 years (27–75). In all cases anti striated‐muscle and acetylcholine‐receptor antibodies were present. Thymectomy was performed 1.4 years (1–3) after diagnosis of myasthenia gravis; histology revealed invasive mixed lymphocytic/epithelial (1), invasive epithelial (1) and non‐invasive lymphocytic/epithelial (1) cell thymoma. All patients were receiving pyridostigmine, prednisolone and azathioprine at the time nephrotic syndrome developed (a mean of 2 years after thymectomy). Renal biopsy demonstrated a minimal change nephropathy alone in all three. Remission following increased steroids occurred in two despite continuing azathioprine. Myasthenic symptoms remained stable throughout. The third patient died 3 weeks after onset of nephrotic syndrome. The cause of the nephrotic syndrome is uncertain, but an immune mechanism, possibly in genetically predisposed individuals, is perhaps most likely.
Interhemispheric coherence analysis of scalp electroencephalograms (EEGs) in three intractable epileptic patients before and after surgical section of the anterior part of the corpus callosum was performed. Equidistant EEG periods recorded under resting conditions free of interictal epileptic activity and periods with generalized spike‐and‐wave discharges were investigated. Mean coherence values for five frequency EEG bands (delta, theta, alpha, beta 1 and beta 2) before and after corpus callosotomy were compared with each other and statistically evaluated. Anterior callosotomy led, in all cases, to a decrease of interhemispheric EEG coherence in most localizations, with the most profound decreases in the region corresponding to the section. These results support the hypothesis that the corpus callosum plays an important role in resting interhemispheric integration and EEG synchronization, similar to its central role in propagation of specific epileptic activity.
Despite great progress in the diagnosis and therapy of multiple sclerosis (MS) some problems remain unsolved. For example, should immunologically negative cases also be classified as multiple sclerosis? In addition, we are still waiting for medication which will have a definite impact on the natural course of the disease.