1 Paediatric Anaesthesia : Review article Cerebral palsy and anaesthesia PORANEE WONGPRASARTSUK* AND JOHN STEVENS *Department of Anaesthesia, Great Ormond Street Hospital for Children, London and Department of Anaesthesia, John Radcliffe Hospital, Oxford, UK Introduction Cerebral palsy (CP) is an umbrella term covering a group of nonprogressive, but often changing, motor impairment syndromes secondary to lesions or anomalies of the brain arising in the early stages of its development (1). The clinical picture may vary considerably, ranging from mild monoplegia with normal intellect to severe total body spasticity and mental retardation. The common denominator is the presence of a motor disorder arising from a brain lesion or anomaly that is nonprogressive and presents early in life (2). Advances in medical care, changes in society s attitudes to infants, children and adults with disabilities have redirected the long-term management of CP from passive, supportive care to a more active, interventionist treatment. As a result, anaesthetic involvement in the care of patients, particularly children, with CP has increased. This review aims to discuss recent developments in the aetiology, diagnosis and anaesthetic related management of CP. Aetiology and risk factors Epidemiological surveillance programmes indicate the prevalence of CP in the developed world is relatively static at per 1000 live births among babies of normal birth weight (3,4). With advances in neonatal medicine and improved survival of premature infants, there is some evidence indicating an increase in the prevalence of CP in low birth weight children (5). However, this contrasts with a recent survey of rates of cerebral palsy Scotland and England, suggesting that the birthweight specific Correspondence to: Poranee Wongprasartsuk, Nuffield Department of Anaesthetics, Level 1, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK ( prevalence of CP has remained stable over a 5-year period of surveillance (4). The aetiology of CP is probably multifactorial, and the contribution of specific causes still debated. A small percentage, recently estimated at 6% (95% CI 0 15%), of cases is thought to be caused by intrapartum hypoxia, with the most common presentation in this group being spastic quadriplegia and, rarely, dyskinesia (6,7). In term and near term infants, approximately 50% of spastic CP is caused by prenatal problems: cerebral maldevelopment, prenatal stroke, prenatal infection (including toxoplasmosis, rubella, cytomegalovirus, herpes virus, i.e. TORCH) or recognized genetic disorders in which spasticity is a feature (8). Pure ataxic or dyskinetic CP is probably genetic in origin (9). Because of the retrospective nature of the diagnosis of CP, causality in individual cases is usually difficult to establish. For infants born at over 34 weeks gestation, a recent international consensus statement outlines criteria for defining an acute intrapartum hypoxic event (birth asphyxia) as causation of CP (7). Premature infants may be different to term infants. In preterm babies, several hypotheses have been put forward to explain the development of CP. It may be the result of an ischaemic insult in utero, leading to both premature birth and damage to cerebral white matter (10). Immature babies are vulnerable to cerebral haemorrhage and ischaemia, with intrapartum injury more likely (11). An alternative and perhaps more realistic explanation is that CP is a final common endpoint of a number of factors operating at different stages of early development, rather than any specific event (12). In general, the recognized risk factors for the development of CP in the premature infant include: perinatal hypoxia, prenatal infection, congenital abnormalities, trauma and genetic predisposition. 296 Ó 2002 Blackwell Science Ltd
2 CEREBRAL PALSY AND ANAESTHESIA 297 Interestingly, a protective factor against the development of CP in premature infants may be maternal hypertension (13). Classification of cerebral palsy Cerebral palsy, being a collective term for a variety of syndromes and lesions, is most easily classified according to the predominant motor defect. Although there is disagreement over the nomenclature, description of the motor defect as the main feature of the diagnostic label has significant advantages, including the planning of resources to care for children and adults with this group of disabilities (2). The motor defect may be spasticity, ataxia or dyskinesia. Spasticity can range from mild monoplegia to severe quadriplegia and total body spasticity. Accompanying the motor defect may be varying degrees of intellectual capacity, from normal intellect to severe handicap. Speech may also be impaired as part of the motor or intellectual disability. Goals of treatment Modern care of children with CP is an integrated approach, combining community and hospital care. Medical and surgical treatment is closely integrated with physical therapies such as massage and splinting. The aims of skeletal treatment are to improve function, mobility and communication by maintaining or improving range of motion and reducing the severity of contracture, spasms and pain. The overall goal is to maintain or improve independence and, in severely disabled children, improve ease of care. Assessments regularly monitor motor function, independence, self-care and general care. Scoring systems such as the Ashworth Scale (monitoring muscle tone, Table 1) are useful tools to monitor function. Regular gait assessment in ambulatory patients will detect deterioration in function early enough to allow noninvasive therapy. Currently, a more aggressive approach to nutritional care helps prevent malnutrition, infection and renal complications. Medical therapy Medical treatment for controlling spasticity, preventing contractures, may reduce the need for Table 1 Ashworth Scale scoring system Ashworth Score surgical correction, but must be introduced early. There is variation in the aggressiveness of such treatment in different centres. Medications act either centrally or peripherally, and their adverse effects are usually an extension of their actions, predictable with knowledge of the mechanism of action. Centrally active agents Degree of muscle tone 1 No increase in tone 2 Slight increase in tone, giving a catch when the affected part(s) is moved in flexion or extension 3 More marked increase in tone but affected part(s) easily flexed or extended 4 Considerable increase in tone; passive movements difficult 5 Affected part(s) rigid in flexion or extension Drugs modulating central triggers of spasticity may be administered orally or intrathecally. Drugs used in the treatment of spasticity are baclofen, diazepam (and other benzodiazepines), vigabatrin and tizanidine. All of these drugs have dose proportional side-effects, predominantly sedative; therefore, intrathecal administration has recently been advocated to minimize the total dose given and target the site of action. Baclofen, 4-chlorophenyl-GABA, is an agonist at GABA-b receptor, acting in the spinal cord to inhibit the release of excitatory neurotransmitters (aspartate and glutamate), reducing muscle tone. Of the medications used in the treatment of spasticity, baclofen is the only one currently used intrathecally with demonstrable, though unpredictable, reduction in spasticity. Given intrathecally, it reaches more than 10 times the CSF concentration compared to oral administration (14). Intrathecal baclofen may be administered as a bolus (usually as a test dose to identify nonresponders) or via an implanted, programmable pump. The major advantage of continuous intrathecal baclofen infusion is titratability. Some children, with underlying muscle weakness actually rely on a degree of spasticity to walk or stand. These children may benefit from a mild reduction of spasticity, but it would be detrimental to their function to ablate all spasticity. Common
3 298 P. WONGPRASARTSUK AND J. STEVENS adverse effects of orally administered baclofen include drowsiness, ataxia, dizziness and lethargy. Problems with the intrathecal route include mechanical problems with the pump, reservoir and infection. Adverse effects of intrathecal baclofen are an extension of effects of the oral route and also include confusion and hypotonia (14). Diazepam and other benzodiazepines enhance presynaptic GABA-a mediated inhibition of neurotransmission and are given orally to treat spasticity. Common adverse problems of benzodiazepines are lethargy and development of tolerance. Vigabatrin (c-vinyl GABA) is a GABA transaminase inhibitor. Originally developed for the treatment of epilepsy, it prevents the breakdown of GABA and can be used to treat spasticity. Tizanidine, a derivative of the a 2 agonist clonidine, probably inhibits the central release of aspartate and is effective in reducing spasticity. Common problems reported are dry mouth and a feeling of muscle weakness. Uncommonly, it causes reversible abnormalities in liver function tests, which disappear on cessation of the drug. It may also cause mild lowering of blood pressure. Drug induced hepatitis and hallucinations are rare, serious side-effects (15). Intrathecal administration of this drug is under investigation. Peripherally acting drugs Botulinum toxin type A (botulinum toxin) is a widely used treatment for spasticity in CP. Administered by injection into target muscles, it produces a functional denervation of the muscle by preventing presynaptic release of acetylcholine from the motor end plate. The degree of paralysis is dose dependent and the duration of effect depends on the rate of terminal sprouting and the generation of new motor end plates. Onset of action is within 1 3 days and the expected duration of effect is 3 4 months. Because of the high affinity of botulinum toxin for the neuromuscular junction, systemic spread is negligible and side-effects are few providing the total dose at any one time is closely controlled. Muscles to be injected are usually identified using a combination of clinical examination and, where appropriate, gait analysis. Reduction in muscle tone, improved range of motion, improved ease of care, reduced pain from contractures and improved muscle growth are all reported benefits of intramuscular botulinum toxin (16). Two recent randomized, double-blind, placebo-controlled clinical trials have demonstrated the effectiveness of botulinum toxin A in reducing equinus foot deformity due to spasticity (17) and, also, that botulinum toxin A, administered 5 10 days preoperatively, can reduce postoperative pain secondary to muscle spasm (18). Occasionally, underlying weakness is revealed by injection and the child s overall condition is compromised. Injections are performed under topical or local anaesthesia, sedation or general anaesthesia. Two commercial preparations are available for use: Botox TM and Dysport TM. They are not equipotent. For injections into calf muscles, the recommended dose of Dysport TM begins with a starting dose of 30 UÆkg 1 in two divided doses, up to a maximum of 1000 UÆkg 1. In contrast, the recommended dose of Botox TM is 4 UÆkg 1 divided in two doses. There are no published reports of interaction with commonly used general anaesthetic agents when botulinum toxin is used in this way. Possible unwanted effects include leg cramps, weakness and lethargy (15). Overdose may cause respiratory muscle weakness. Accidental overdose requiring respiratory support and local paralysis leading to swallowing difficulties have also been reported (J.S. personal communication). Clinical trials have not reported adverse effects or drug interactions. Dantrolene inhibits calcium uptake by skeletal muscle sarcoplasmic reticulum and relaxes tonically active muscle. Baclofen is sometimes given orally in the treatment of spasticity. It has no effect on the neural mechanism of spasticity. Common adverse effects are muscle weakness, diarrhoea, malaise, nausea and skin rash. Liver function tests may become abnormal (14,15). Anaesthesia and surgical interventions Children with CP present for surgery for a variety of reasons, ranging from general surgical conditions to particular interventions because of cerebral palsy. Common surgical procedures include dental procedures (restorative procedures and extractions), surgery to control gastro-oesophageal reflux (GOR), feeding gastrostomies, tracheostomies, spinal surgery, neurosurgical procedures to control spasticity (e.g. highly selective dorsal rhizotomy) and a variety
4 CEREBRAL PALSY AND ANAESTHESIA 299 of upper and lower limb orthopaedic bony and soft tissue procedures. These procedures are offered to a broad cross-section of patients and may be indicated for improvement in mobilization or ease of care, in keeping with the broad goals of managing children with CP. Preoperative assessment Medical, communication, general care problems and social issues often complicate preoperative assessment of children with cerebral palsy. Often, children have undergone repeated procedures; hence the impact of previous experience is considerable. As with all preoperative assessment, the aims are to ensure the patient s general medical condition is optimized, a reasonable evaluation of perioperative risk is discussed and the anaesthetic procedure explained. Although optimization of medical condition and explanation of anaesthetic procedure may be relatively straightforward, evaluation of perioperative risk is much more difficult, especially in children with severe disability. Particular problems with respect to patients with CP are protean. They include a range of communication difficulties; the presence of scoliosis perhaps restricting ventilation; GOR (some have had a corrective procedure); contractures restricting access for examination and positioning; decubitus ulcers and skin infections; presence of gastrostomy or tracheostomy and problems associated with malnutrition. Medical comorbidities, in particular epilepsy and chest infection, need to be evaluated. A clear history of current medication should be elicited, particularly of antacids and anticonvulsants. Cisapride, commonly used for medical treatment of GOR in these patients has been reported to be associated with prolonged QT interval and life threatening ventricular dysrhythmias. However, if liver function is normal, in the absence of drug interactions impairing metabolism of cisapride and using modest, accurately measured doses, ventricular dysrhythmia is unlikely to be a concern (19,20). There is evidence that sodium valproate may increase bleeding due to platelet dysfunction, thrombocytopaenia or aquired von Willebrand factor deficiency type 1. These problems are probably dose dependent, usually seen at serum valproate levels >100lgÆml 1. Dose reduction and rarely discontinuation of sodium valproate will normalize these coagulation problems. Preoperative coagulation tests are suggested for children taking long-term sodium valproate (21). Continuation of regular medications such as antispasmodics and anticonvulsants in the perioperative period is important for symptom stability and prevention of acute withdrawal problems. Preoperative assessment should also include screening questions for latex allergy. Children with CP, because of multiple surgical procedures and exposure to latex allergens from an early age, are at increased risk of developing latex allergy (22). Screening questions should be explicitly asked. These include direct enquiry about respiratory symptoms, such as wheeze or allergic rhinitis, cutaneous manifestations, such as rash, itch, oedema or swelling on exposure to latex products, as well as adverse reactions during previous anaesthesia. If perioperative anaphylaxis occurs, latex allergy should be considered. Allergist follow-up is vital in establishing the cause of anaphylaxis after the acute event. Recent attempts have been made to elucidate preoperative predictors of complications. Stasilkelis et al. concluded that ambulatory function correlates well with risk of complications following osteotomies. In this series of 79 patients followed up for at least 1 year, a nonambulatory patient with a gastrostomy or tracheostomy was at greater risk of complications. Recorded complications of surgery were death (three children), fracture and decubitus ulcer. Twenty patients were reported to have had at least one complication (23). Lipton et al. (24) using a retrospective medical record review, developed a preoperative risk score (ORS) and postoperative complication score (POCS). The ORS was primarily a reflection of severity of neurological involvement, with a higher ORS indicating greater operative risk. Factors taken into account in calculating the ORS were ambulation status, mental retardation, speech, feeding ability, care (home or institutional), weight for age, degree of deformity, medical and surgical history in the past year. The POCS represented severity of postoperative complication, a higher score indicating a more severe complication. In this study of 107 patients undergoing spinal fusion, the authors suggest the ORS is positively correlated with the severity of
5 300 P. WONGPRASARTSUK AND J. STEVENS postoperative complications. In addition, spinal deformity greater than 70 was associated with a significantly higher POCS. There appeared to be no significant differences in POCS between patients having posterior spinal fusion alone and patients having both anterior and posterior spinal fusion. The scoring systems developed in this study represent an important step forward in evaluating perioperative risk of CP patients. However, external validation is required on a similar group of patients with further validation on another group of CP patients, undergoing different surgeries, to extend generalisability. The use of a preoperative feeding gastrostomy improves nutritional status and may decrease postoperative infection and improve wound healing. It will also allow good perioperative fluid management, decreasing the risk of renal damage and circulatory complications such as deep venous thrombosis. Anaesthetic care Induction of anaesthesia may be challenging due to lack of cooperation, communication difficulties and difficult intravenous (i.v.) access. This is particularly so in those children who have previously been in special care baby units or neonatal intensive care; who may have previously used and scarred veins. If i.v. induction of anaesthesia is planned, all commonly used agents are suitable, although propofol appears to be more painful in these patients. Patients may be severely affected by drooling because of decreased ability to swallow secretions, making gaseous induction of anaesthesia both messy and risky. A drying premedication such as atropine can be beneficial but may also increase the risk of chest infection by thickening lung secretions. The increased incidence of GOR may sway anaesthetists to choose a rapid sequence induction, although there is no evidence to suggest that this confers any safety. The presence of a second pair of hands is often helpful to establish i.v. access. Airway management in the presence of increased incidence of GOR in this group of patients varies. Many anaesthetists choose a laryngeal mask airway when clinically appropriate in conjunction with a nasal or oral gastric tube aspirated and left on free drainage, others chose a tracheal tube routinely. The authors are not aware of published comparative studies of different airway techniques in this group of patients. Due to clinical variation, the wide range of surgical interventions, large variation in severity of CP and severity of GOR, such studies may be challenging to undertake. Studies of muscle relaxants in children with CP indicate a slight sensitivity to succinylcholine. In a dose response study by Theroux et al. a slightly lower ED 50 was found compared to historical controls. Although this difference was detected, it is unlikely to be clinically significant. This finding may be due to different structure and composition of the neuromuscular junction (25) or an upregulation of acetylcholine receptors (AchR s), perhaps secondary to chronic anticonvulsant medication (26). Vecuronium resistance has also been demonstrated in CP. In a comparative study, using prospective controls, Moorthy et al. showed a significant resistance to vecuronium. The time from administration of 0.1 mgækg 1 to 25% recovery of control twitch height in children with CP was less than half the time for normal children. The mechanism of resistance to vecuronium is unclear because all children in this study were severely affected by CP and taking longterm anticonvulsant medication. Postulated mechanisms include drug interaction with anticonvulsant medication (increased hepatic clearance, AchR upregulation) and chronic immobilization (27). For volatile anaesthetics, minimum alveolar concentration (MAC) for anaesthesia may be decreased. The MAC of halothane has been shown to be 20% lower in children with CP, and a further 10% lower in those currently taking anticonvulsants (28). Most major surgical procedures undertaken in children with CP are amenable to combined general anaesthesia and regional analgesia. Epidural analgesia, in particular, continued into the postoperative period will diminish both postoperative pain and muscle spasm. Continuous infusion of epidural bupivacaine (0.1%) and fentanyl (2 lgæml 1 ), monitored by an acute pain service, is thought to provide better analgesia with few side-effects compared to intermittent boluses of epidural morphine (29) or intravenous opioid infusions. The addition of clonidine may give added control of postoperative spasm. In the control of postoperative pain following selective posterior rhizotomy in the lumbar region (to improve gait or stance), epidural opioids, morphine in particular, remain the mainstay of treatment (30).
6 CEREBRAL PALSY AND ANAESTHESIA 301 There are pros and cons of awake versus asleep insertion of epidural catheters. Awake placement of epidural catheters is not a practical or safe option in this group of patients. There is also a high incidence of scoliosis. Because of these problems, an experienced epiduralist should be involved in placement of the epidural. It is important to remember that scoliosis is also a torsional deformity, and the epidural performed accordingly. Perioperative hypothermia is a significant problem, especially when age, understanding and ability to cooperate are limited during induction of anaesthesia. During the performance of some anaesthetic procedures, children may lose heat quickly. (e.g. placement of an epidural catheter). Further exposure to a cool operating theatre may occur during positioning for surgery and subsequent changes in position, such as during a multilevel orthopaedic soft tissue release procedure. Prolonged insufflation of the abdomen or thorax during laparoscopic surgery may also increase heat loss. The increased likelihood of hypothermia is unavoidable, but can be minimized by humidification of airway gases, use of low fresh gas flows, warmed intravenous fluids, avoidance of a cold operating room and using active warming methods such as forced air warming blankets. If active warming methods are used, it is important to monitor core temperature because overheating is a potential hazard. Patient positioning may be problematic, with contractures often not allowing support by conventional operating tables and supports. Pressure sores and nerve damage are a very real possibility. Children with CP are especially at risk because of their poor nutritional status and the length of many operations. A comfortable, malleable support such as a vacuum bag is very helpful. Extensive plaster casting is an important aspect of skeletal treatment in CP. However, extensive casting can mask considerable blood loss and, when combined with epidural analgesia, may make compartment syndromes more difficult to detect. This is particularly so following tibial osteotomy, where there is a significant risk of compartment syndrome. Plaster jackets and hip spicas are associated with mesenteric occlusion and acute gastric dilatation, and so a nasogastric tube should be inserted routinely. Chronic low fluid intake, combined with preoperative fasting, means that children with CP are at risk of prerenal, renal failure. The perioperative impact of this can be lessened by careful monitoring of urine output. Insertion of a urinary catheter should be considered to monitor urine output, especially for long or difficult procedures involving significant blood loss and fluid shifts. Specific surgical procedures Inguinal hernia repair Often, the first time a child with CP attends for anaesthetic care is for hernia repair early in life. Up to 30% of boys with birth weight < 2000 g and likely to be at risk of CP may have an inguinal hernia (31). It is postulated this is due to increased intraabdominal pressure associated with increased tone in the abdominal wall. In the premature neonate, the standard practice in most UK paediatric centres is to repair the inguinal hernia just prior to anticipated discharge home. There is some evidence that earlier repair may improve comfort, handling and nutrition and does not increase morbidity. Spinal anaesthesia, without sedation for the ex-premature baby was, in recent years, advocated because it may reduce the incidence of postoperative apnoea. There is limited evidence to support this view. A comparative study in high-risk infants undergoing inguinal hernia repair suggests potential benefit in reducing the incidence of postoperative apnoea. However, it also illustrates many of the major problems that prevent awake spinal anaesthesia for this group of patients from being widely adopted. In a group of 24 infants the problems were technical failure to perform the spinal in four infants; two or more attempts in five; supplemental general anaesthesia in six and surgical difficulty requiring physical restraint because of excessive upper limb movement in 14 infants (32). During a difficult hernia repair, spinal anaesthesia may not last long enough, especially if bilateral repair is required. General anaesthesia can be supplemented by ilioinguinal nerve block or infiltration of local anaesthetic in unilateral repair. In bilateral repairs, caudal block is beneficial. Antireflux surgery GOR is a common problem among children with CP, frequently requiring surgical correction. An open
7 302 P. WONGPRASARTSUK AND J. STEVENS operation is associated with considerable morbidity and laparoscopic surgery is now probably the approach of choice in most situations. The physiological changes associated with pneumoperitoneum in children have been described. Early experience with laparoscopic Nissen fundoplication suggests children are well managed with oral and rectal analgesia postoperatively. In addition, the need for postoperative high dependency and intensive care appears to be minimal (33). Although there is less postoperative pain with this approach, epidural analgesia may still be useful in preventing painful postoperative spasms. Scoliosis surgery Scoliosis surgery is associated with an acute, sometimes prolonged deterioration in respiratory function, even if thoracotomy is not performed. Recently, some surgeons have adopted a thoracoscopic approach to anterior release in an attempt to reduce pulmonary morbidity. Such surgery in severe CP should not be undertaken lightly, and only in a facility with full intensive care provision. Postoperative nasal continuous positive airway pressure (CPAP) may help to prevent respiratory complications. The occasional patient will need long-term ventilation, perhaps even tracheostomy during the weaning process. Preoperative respiratory function tests are unreliable in this scenario and not predictive of outcome. Ethical considerations In a child severely affected by cerebral palsy, decisions about invasive procedures and the use of increasingly scarce intensive care facilities are difficult to make. Once invasive therapy has been embarked upon, it is difficult to judge when the next step is a step too far. Each procedure needs to be considered on its merits; the likelihood of survival and morbidity, as well as the likelihood of improving quality of care and life. It is important for surgeons to be realistic about the likely achievements of the procedure and for anaesthetists to be realistic about the likelihood of anaesthesia related morbidity. Only then can parents (guardians) approach giving truly informed consent for many of these procedures. A particularly contentious subject area of consent is for anaesthesia administered to facilitate magnetic resonance imaging (MRI). MRI has become a compulsory investigation in the pursuit of litigation claims related to CP and causation. Many law firms will not consider a case before an MRI has been performed and reported on by a recognized expert. Although the anaesthetic risk is small, it exists. This is a difficult ethical dilemma as the anaesthetic is not administered for a therapeutic reason and the test (MRI) may lead to failure of the compensation claim. Conclusions In summary, cerebral palsy is currently managed by combined physiotherapy, medical and surgical approaches. The aim of such coordinated care is to significantly improve quality of life and quality of care. Anaesthetic involvement may be in the operating room, in intensive care or providing technical support for insertion of spinal infusing devices in medical therapy. Modern medical advances have enabled more aggressive and invasive care. The challenge for all those caring for patients with CP is to consider the ethics of embarking upon highly invasive care, with marginal benefit to the patient. References 1 Mutch I, Alberman E, Hagberg B et al. Cerebral palsy epidemiology: where are we now and where are we going? Dev Med Child Neurol 1992; 34: Badawi N, Watson L, Petterson B et al. What constitutes cerebral palsy? Dev Med Child Neurol 1998; 40: Paneth N, Stark RI. Cerebral palsy and mental retardation in relation to indicators of perinatal asphyxia. Am J Obstet Gynecol 1983; 147: Pharoah POD, Cooke T, Johnson MA et al. Epidemiology of cerebral palsy in England and Scotland Arch Dis Child Fetal Neonatal Ed 1998; 79: F21 F25. 5 Dite GS, Bell R, Reddihough DS et al. Antenatal and perinatal antecedents of moderate and severe spastic cerebral palsy. Aust NZ J Obstet Gynaecol 1998; 38: Nelson KB, Grether JK. Potentially asphyxiating conditions and spastic cerebral palsy in infants of normal birthweight. Am J Obstet Gynecol 1998; 179: MacLennan A, International Cerebral Palsy Task Force. A template for defining a causal relation between acute intrapartum events and cerebral palsy: international concensus statement. BMJ 1999; 319: Nelson KB, Grether JK. Maternal infection and cerebral palsy in infants of normal birthweight. JAMA 1997; 278: Steinlin M. Non-progressive congenital ataxias. Brain Dev 1998; 20:
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