Inventory of Non-Ataxia Signs (INAS): validation of a new clinical assessment instrument.

Although ataxia is by definition the prominent symptom of ataxia disorders, there are various neurological signs that may accompany ataxia in affected patients. Reliable and quantitative assessment of these signs is important because they contribute to disability, but may also interfere with ataxia. Therefore we devised the Inventory of Non-Ataxia Signs (INAS), a list of neurological signs that allows determining the presence and severity of non-ataxia signs in a standardized way. INAS underwent a rigorous validation procedure that involved a trial of 140 patients with spinocerebellar ataxia (SCA) for testing of inter-rater reliability and another trial of 28 SCA patients to assess short-term intra-rater reliability. In addition, data of the ongoing EUROSCA natural history study were used to determine the reproducibility, responsiveness and validity of INAS. Inter-rater reliability and short-term test-retest reliability was high, both for the total count and for most of the items. However, measures of responsiveness, such as the smallest detectable change and the clinically important change were not satisfactory. In addition, INAS did not differentiate between subjects that were subjectively stable and those that worsened in the 2-year observation period. In summary, INAS and INAS count showed good reproducibility, but unsatisfactory responsiveness. The present analysis and published data from the EUROSCA natural history study suggest that INAS is a valid measure of extracerebellar involvement in progressive ataxia disorders. As such, it is useful as a supplement to the measures of ataxia, but not as a primary outcome measure in future interventional trials.

The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: a 2-year follow-up study.

OBJECTIVE: To obtain quantitative data on the progression of the most common spinocerebellar ataxias (SCAs) and identify factors that influence their progression, we initiated the EUROSCA natural history study, a multicentric longitudinal cohort study of 526 patients with SCA1, SCA2, SCA3, or SCA6. We report the results of the 1- and 2-year follow-up visits. METHODS: As the primary outcome measure we used the Scale for the Assessment and Rating of Ataxia (SARA, 0-40), and as a secondary measure the Inventory of Non-Ataxia Symptoms (INAS, 0-16) count. RESULTS: The annual increase of the SARA score was greatest in SCA1 (2.18 ± 0.17, mean ± SE) followed by SCA3 (1.61 ± 0.12) and SCA2 (1.40 ± 0.11). SARA progression in SCA6 was slowest and nonlinear (first year: 0.35 ± 0.34, second year: 1.44 ± 0.34). Analysis of the INAS count yielded similar results. Larger expanded repeats and earlier age at onset were associated with faster SARA progression in SCA1 and SCA2. In SCA1, repeat length of the expanded allele had a similar effect on INAS progression. In SCA3, SARA progression was influenced by the disease duration at inclusion, and INAS progression was faster in females. CONCLUSIONS: Our study gives a comprehensive quantitative account of disease progression in SCA1, SCA2, SCA3, and SCA6 and identifies factors that specifically affect disease progression.

Responsiveness of different rating instruments in spinocerebellar ataxia patients.

OBJECTIVE: To determine the longitudinal metric properties of recently developed clinical assessment tools in spinocerebellar ataxia (SCA). METHODS: A subset of 171 patients from the EUROSCA natural history study cohort (43 SCA1, 61 SCA2, 37 SCA3, and 30 SCA6) were examined after 1 year of follow-up. Score changes and effect size indices were calculated for clinical scales (Scale for the Assessment and Rating of Ataxia [SARA], Inventory of Non-Ataxia Symptoms [INAS]), functional tests (SCA Functional Index [SCAFI] and components), and a patient-based scale for subjective health status (EQ-5D visual analogue scale [EQVAS]). Responsiveness was determined in relation to the patient's global impression (PGI) of change and reproducibility described as retest reliability for the stable groups and smallest detectable change. RESULTS: Within the 1-year follow-up period, SARA, INAS, and SCAFI but not EQVAS indicated worsening in the whole group and in the groups with subjective (PGI) worsening. SCAFI and its 9-hole pegboard (9HPT) component also deteriorated in the stable groups. Standardized response means were highest for 9HPT (-0.67), SARA (0.50), and SCAFI (-0.48) with accordingly lower sample size estimates of 143, 250, or 275 per group for a 2-arm interventional trial that aims to reduce disease progression by 50%. SARA and EQVAS performed best to distinguish groups classified as worse by PGI. All scales except EQVAS reached the criterion for retest reliability. CONCLUSION: While both the Scale for the Assessment and Rating of Ataxia and the SCA Functional Index (SCAFI) (and its 9-hole pegboard component) had favorable measurement precision, the clinical relevance of SCAFI and 9-hole pegboard score changes warrants further exploration. The EQ-5D visual analogue scale proved insufficient for longitudinal assessment, but validly reflected patients' impression of change.

SCA Functional Index: a useful compound performance measure for spinocerebellar ataxia.

OBJECTIVE: To evaluate the usefulness of functional measures in patients with spinocerebellar ataxia (SCA). METHODS: We assessed three functional measures-8 m walking time (8MW), 9-hole peg test (9HPT), and PATA repetition rate-in 412 patients with autosomal dominant SCA (genotypes 1, 2, 3, and 6) in a multicenter trial. RESULTS: While PATA rate was normally distributed (mean/median 21.7/20.5 per 10 s), the performance times for 8MW (mean/median 10.8/7.5 s) or 9HPT (mean/median 47.2/35.0 s in dominant, 52.2/37.9 s in nondominant hand) were markedly skewed. Possible learning effects were small and likely clinically irrelevant. A composite functional index (SCAFI) was formed after appropriate transformation of subtest results. The Z-scores of each subtest correlated well with the Scale for the Assessment and Rating of Ataxia (SARA), the Unified Huntington's disease Rating Scale functional assessment, and disease duration. Correlations for SCAFI with each of these parameters were stronger (Pearson r = -0.441 to -0.869) than for each subtest alone. Furthermore, SCAFI showed a linear decline over the whole range of disease severity, while 9HPT and 8MW had floor effects with respect to SARA. Analysis of possible confounders showed no effect of genotype or study site and only minor effects of age for 8MW. CONCLUSION: The proposed functional measures and their composite SCAFI have favorable properties to assess patients with spinocerebellar ataxia.

Spinocerebellar ataxia types 1, 2, 3, and 6: disease severity and nonataxia symptoms.

OBJECTIVE: To identify factors that determine disease severity and clinical phenotype of the most common spinocerebellar ataxias (SCAs), we studied 526 patients with SCA1, SCA2, SCA3. or SCA6. METHODS: To measure the severity of ataxia we used the Scale for the Assessment and Rating of Ataxia (SARA). In addition, nonataxia symptoms were assessed with the Inventory of Non-Ataxia Symptoms (INAS). The INAS count denotes the number of nonataxia symptoms in each patient. RESULTS: An analysis of covariance with SARA score as dependent variable and repeat lengths of the expanded and normal allele, age at onset, and disease duration as independent variables led to multivariate models that explained 60.4% of the SARA score variance in SCA1, 45.4% in SCA2, 46.8% in SCA3, and 33.7% in SCA6. In SCA1, SCA2, and SCA3, SARA was mainly determined by repeat length of the expanded allele, age at onset, and disease duration. The only factors determining the SARA score in SCA6 were age at onset and disease duration. The INAS count was 5.0 +/- 2.3 in SCA1, 4.6 +/- 2.2 in SCA2, 5.2 +/- 2.5 in SCA3, and 2.0 +/- 1.7 in SCA6. In SCA1, SCA2, and SCA3, SARA score and disease duration were the strongest predictors of the INAS count. In SCA6, only age at onset and disease duration had an effect on the INAS count. CONCLUSIONS: Our study suggests that spinocerebellar ataxia (SCA) 1, SCA2, and SCA3 share a number of common biologic properties, whereas SCA6 is distinct in that its phenotype is more determined by age than by disease-related factors.

Scale for the assessment and rating of ataxia: development of a new clinical scale.

OBJECTIVE: To develop a reliable and valid clinical scale measuring the severity of ataxia. METHODS: The authors devised the Scale for the Assessment and Rating of Ataxia (SARA) and tested it in two trials of 167 and 119 patients with spinocerebellar ataxia. RESULTS: The mean time to administer SARA in patients was 14.2 +/- 7.5 minutes (range 5 to 40). Interrater reliability was high, with an intraclass coefficient (ICC) of 0.98. Test-retest reliability was high with an ICC of 0.90. Internal consistency was high as indicated by Cronbach's alpha of 0.94. Factorial analysis revealed that the rating results were determined by a single factor. SARA ratings showed a linear relation to global assessments using a visual analogue scale, suggesting linearity of the scale (p < 0.0001, r(2) = 0.98). SARA score increased with the disease stage (p < 0.001) and was closely correlated with the Barthel Index (r = -0.80, p < 0.001) and part IV (functional assessment) of the Unified Huntington's Disease Rating Scale (UHDRS-IV) (r = -0.89, p < 0.0001), whereas it had only a weak correlation with disease duration (r = 0.34, p < 0.0002). CONCLUSIONS: The Scale for the Assessment and Rating of Ataxia is a reliable and valid measure of ataxia, making it an appropriate primary outcome measure for clinical trials.

[Clinical picture of spinocerebellar ataxia type I (SCA1)]. / Obraz kliniczny bezladu rdzeniowo-mózdzkowego typu I (SCA1).

Spinocerebellar ataxia is a group of diseases with autosomal dominant inheritance heterogenous both clinically and genetically. So called dynamic mutations underlie most these nosological units. The clinical patterns of various SCA types have not yet been defined completely. The purpose of the present report was description of the typical symptoms and signs of type 1 SCA. Seventeen patients from 13 families (M-2, F-15) were studied clinically in detail. The diagnosis was confirmed by DNA analysis. The assessment included neurological status, cognitive functions, the results of EEG, EMG, SEP, VEP, BAER and MRI examinations. The pedigrees indicated autosomal dominant inheritance pattern. The mean age at onset was 35.5 +/- 6.8 years (range 23-45 years) and it suggested negative correlation with the number of CAG repetitions. Cerebellar syndrome limb and truncal, ataxia and dysarthria was present in all cases. Six patients had nystagmus, 3 had slow saccades, 2 had gaze limitation upward, and lateral and 6 had dysphagia. Signs of pyramidal system involvement were found in 10 cases, one had athetotic movements, one had orthostatic hypotension. Two patients had dementia features, 9 had some decline of intellectual functions, mainly with difficulties of memorization, learning and concentration. In 16 cases MRI demonstrated vermis atrophy and atrophy of cerebellar hemispheres, 14 had fourth ventricle dilatation, 8 had flattening of pons base, 8 had narrowing of cervical spinal cord, 8 had dilated CSF spaces over frontal lobes and in 6 cases lateral ventricles were dilated. Electrophysiological peripheral nervous system investigations showed in 16 cases long-standing damage to the motor and sensory peripheral neurons at the level of nerve trunks, more pronounced in sensory nerves. In 13 cases peripheral neuron damage was subclinical. SEP showed in all patients disturbed function of ascending sensory pathways at peripheral and spinocortical levels.

[Polyneuropathy in the course of Hodgkin's disease: case report]. / Polineuropatia w przebiegu choroby Hodgkina -- opis przypadku.

Polyneuropathy in neoplastic process practically may occur in every stage, before clinical signs, together with clinical signs and in the last period. In some percent of patients polyneuropathy may outstrip manifestation of neoplastic process even for many years. We present a 61-year-old patient in whom signs of polyneuropathy appeared before the signs of essential disease - Hodgkin's disease. Our case confirms the necessity of very careful and precise diagnostics of polyneuropathy with unclear aetiology.

[Dermatomal somatosensory evoked potentials from L3, L4, L5 and S1 spinal roots in healthy subjects]. / Dermatomalne somatosensoryczne potencjaly wywolane z korzeni L3, L4, L5, S1 u osób zdrowych.

Dermatomal somatosensory evoked potentials (DSEPs) were recorded in 62 healthy volunteers aged from 15 to 65 years (mean 36.8 +/- 12.9 years) with height from 1.5 to 1.92m (mean 1.69 +/- 0.10m). The aim of the study was to establish normal values for L3, L4, L5 and S1 dermatomes and to introduce this method for the neurophysiological diagnosis of chronic lumbosacral pain and disc disease. The signature areas of dermatomes in both legs separately were stimulated according to the method described by Sedgwick and Katifi (1985). DSEPs were recorded from the scalp electrodes placed at Cz', referred to Fpz. The latencies and amplitudes of consecutive components of DSEPs: N33, P40, N50, P60, N75 and side to side differences were measured and evaluated. Statistical analysis of the results revealed significant positive correlation of DSEPs latencies as a function of height. The correlation of amplitudes with height was less significant. Age, on other hand, showed only negative correlation with amplitudes of later DSEP components. On the basis of the performed analysis the latency of P40 and amplitude of P40-N50 seem to be the best parameters for the evaluation of pathological DSEPs. The range of normal value of latencies for stimulated roots should be calculated from regression equation with the subject's height. As regards amplitude, side to side mean value difference above two standard deviation appears to be more useful.

Reanimation of the face after facial nerve palsy resulting from resection of a cerebellopontine angle tumour.

Twenty-three patients with facial nerve paralysis following surgery for a cerebellopontine angle tumour had a facial-hypoglossal anastomosis and simultaneous anastomosis of the cervical ansa with the distal stump of the hypoglossal nerve. In 18 patients, simultaneously with the neural anastomoses, additional transpositions of the temporalis and masseter muscles were performed. At follow-up examination 3-87 months after reconstructive surgery, eight patients had House grade II, ten grade III and five grade IV outcome. The EMG evidence of reinnervation was observed 5-11 months after anastomosis. Combination of the facial-hypoglossal anastomosis with simultaneous myoplasty and with anastomosis of the distal hypoglossal nerve stump to the ansa cervicalis provides the advantage of immediate protection against ophthalmic complications, prevents hemiatrophy of the tongue and gives good functional results when reinnervation of the facial muscles takes place.

[Preoperative and intraoperative studies of evoked potentials in patients with spinal cord injury]. / Przed- i sródoperacyjne badanie potencjalów wywolanych u chorych z uszkodzeniem rdzenia.

Preoperative recording of evoked potentials after stimulation of the tibial nerve was followed by similar intraoperative recording in 6 patients with cauda and conus terminalis tumours and 2 patients with intervertebral disc prolapse at lumbar level. The shape and latency of these potentials were sensitive indicators of the level and degree of damage to the nervous elements in this area. The selectivity of the method was significantly higher during intraoperative recording. Monitoring of these potentials may serve for control of the integrity of sensory pathways during neurosurgical interventions.

[Effect of stimulation of the spinal cord on phasic and tonic reflexes in patients with central motor neuron damage]. / Wplyw stymulacji rdzenia kregowego na odruchy fazowe i toniczne u pacjentów z uszkodzeniem centralnego neuronu ruchowego.

Spinal cord stimulation (SCS) is a method enabling the control of increased muscle tonus to be achieved in various spinal cord injuries. Polyelectromyographic (PEMG) methods were used for neurophysiological assessment of the degree of cord damage and persistent spinal reflexes as well as supramedullary influences. The analysed material comprised 40 PEMG records in 19 patients with spastic paraparesis or paraplegia after cord injury, cord tumour or multiple sclerosis. In 15 cases tentative epidural cord stimulation was done and 11 patients received implantation of a system for long-term stimulation. In most cases the epidural electrodes were implanted below the damaged segment, usually in the thoracic part of the cord. Before and after SCS beginning PEMG was done with a 16-channel Mingograph Siemens Elema with simultaneous recording of the responses from the symmetric muscles: quadriceps, semitendinous, adductor femoris, anterior tibialis and triceps surae. The effect of SCS was analysed on exteroceptive and proprioceptive reactions during testing of knee and ankle reflexes, and on the response of the muscles to vibration. In most patients a reduction was observed of the intensity of tendon reflexes, particularly the spread of the reflex to the contralateral extremity was no longer seen. The vibration reflex had a tonic character persisting in 48% of the studied muscles, even in patients with clinically complete transsection of the cord. The change of the character of monosynaptic reflexes and the presence of the vibration reflex suggest that SCS modifies the proprioceptive segmental spinal reactions.

[Somatosensory potentials evoked by stimulation of the median nerves recorded during the operation from the surface of the cerebral cortex in patients with temporal lobe epilepsy]. / Somatosensoryczne potencjaly wywolane draznieniem nerwów posrodkowych rejestrowane sródoperacyjnie z powierzchni kory mózgowej u chorych z padaczka skroniowa.

Somatosensory evoked potentials obtained by stimulation of the median nerve were analysed. The potentials were recorded from 237 points of exposed cortex in 34 patients with temporal lobe epilepsy with epileptogenic focus in the left lobe in 17 cases, and in the right lobe in 17 cases. Only N 20 and P 20 responses were analysed, considering potentials with amplitude above 0.3 uV. No response was obtained from 40.7% of points on the right side, and from 48.7% points on the left. On the right side negative potentials prevailed (56.8%) and on the left side positive potentials were more frequent (32.8%). A characteristic feature of the recorded potentials was their low amplitude and shorter latency of the positive deflection in which they differed from the potentials evoked from the primary sensorimotor cortical representation of the hand. The authors put forward the hypothesis that the recorded potentials are generated by secondary sensory areas and sensory representation in the external cortex of the temporal lobes.

[Signs of aging of the peripheral motor neurons based on electromyographic studies]. / Objawy starzenia sie ruchowego neuronu obwodowego w zapisach elektromiograficznych.

Sixty healthy subjects of either sex aged from 15 to 75 years were examined. Electromyographic records were obtained by the one-step automatic histogram analysis method according to Hausmanowa-Petrusewicz and Kopec, and by the classic method of quantitative electromyography. In each case 4 muscles were examined: deltoid (Dlt), rectus m. of thigh (RF), short abducens m. of thumb (APB), short extensor of fingers (EDB). In both methods the mean duration of motor unit potential, the amplitude of single motor unit potential, the amplitude of effort record and the density of potentials were determined and correlated with age. The duration of motor unit potentials in the classic EMG record was correlated statistically significantly with the age in all muscles (in agreement with Buchthal). The number of parameters correlating with age and the significance of this correlation were highest in the records from lower extremity muscles, particularly in EDB. This could depend on age-related summation of subclinical signs of peroneal nerve damage, since this nerve is exposed to frequent microtraumas. However, in 4 examined healthy muscles the intensity of changes in EMG parameters correlating significantly with age seems to be related to the length of the muscles innervating them, and to the processes of ageing of the neuromuscular apparatus and blood vessels supplying it. Extensor muscle (EDB) innervated by motor neurons with longest axons may be the most sensitive indicator of the processes of ageing of peripheral motor neurons.