Three decades have elapsed since Dawson (1947) recorded the first somatosensory evoked potential (SEP). Simple superimposition of individual responses was possible because the patient had progressive myoclonic epilepsy. In this disease the SEP amplitude is much enhanced (Shibasaki et al, 1978; Kelly et al, 1981). Subsequently Dawson (1951, 1954) presented his averager to the Physiological Society, thereby initiating the present-day explosive growth of evoked potentials.

SEPs are made up of components with varying latencies. The components are best identified by latency and polarity as recorded at the scalp (P = positive and N = negative). Nevertheless, the nomenclature of somatosensory evoked potentials can be extremely confusing, mainly because the same component can have a different polarity depending on the electrode montage used. Generally speaking (but this is not a firm rule), far-field (subcortical) potentials are positive in polarity when a non-cephalic reference is used, whereas these same components have a negative polarity when the reference is on the scalp. It is therefore useful to always indicate the recording montage being employed. In addition, use of absolute latencies in the terminology can cause confusion because they are dependent upon length and body height. For example, the brachial plexus component usually occurs at about 9 msec, but may extend to as long as 11 or more msec in a very tall individual. Subsequent components then become difficult to identify in relation to normal means.

An ultrastructural study of the dorsal sympathetic ganglia, chain, and myenteric plexus is described in the streptozotocin diabetic rat after intermittent insulin treatment. The observations described cover the first two weeks following induction of diabetes in which insulin was administered subcutaneously twice daily. Significant regenerative changes were seen with marked axonal sprouting noted at three days. Degenerative changes were seen to be less severe than those in untreated animals. It is concluded that the improvement in the neuropathic changes with insulin treatment supports a transient primary role of the streptozotocin in causing the neuropathy — but that the subsequent improvement seems to be related to the partial control of the diabetes.

A case of neonatal myasthenia gravis is reported in the infant of an asymptomatic thymectomized mother with comparably elevated acetylcholine receptor (AChR) antibody titers. The mother remained asymptomatic despite elevated antibody titers while the infant became asymptomatic in association with the disappearance of the AChR antibody. It is suggested that the AChR antibody plays an essential role in the development of neonatal myasthenia gravis. It is also suggested that a thymic factor is necessary for the development of clinical symptomatology accounting for the lack of correlation between the clinical state of the mother and infant.

Three chronic alcoholics developed choreiform dyskinesias involving the face, lips, tongue and, in one case, all limbs; 2 patients for the first time, 9 to 10 days after alcohol withdrawal. These abnormalities improved spontaneously with maintained abstinence from alcohol for 2 to 7 weeks. None had a family history of movement disorder, there was no history of other psychoactive drug use or abuse, and there was no evidence of portal-systemic encephalopathy.

We present a working classification of recessively inherited ataxic syndromes based on the use of simple tools available to every clinician: a good history (particularly pinpointing the age of onset) and a good neurological examination (simplified to the verification of the presence of ataxia, deep tendon reflexes in the knee, optic nerve, retinal and/or 8th nerve signs). In the three groups of disorders (non progressive, intermittent or progressive) patients can be hyper/normo reflexic, or they can be hypolareflexic. Six principal types of progressive ataxic disorders are further delineated by the age of onset. Sub-types depend on the presence or absence of eye and ear signs, whereas eponymic or regional denominations are used only for simplicity while awaiting exact delineation of the biochemical defects.

The authors report a case of Charcot-Marie-Tooth disease that mimicked Friedreich’s ataxia and featured impaired tendon reflexes in the limbs, incoordination mimicking cerebellar disease in the extremities, extensor plantar responses on both sides, bilateral foot deformity, impaired position sense in the toes, absent vibratory sense in the distal parts of the legs and minimal distal weakness with wasting. Motor conduction velocity in the upper limbs was substantially reduced.

Other cases similar in nature reported in the literature resemble spino-cerebellar degeneration in general, and Friedreich’s ataxia, in particular. It is emphasized that the natural history, EMG, motor conduction velocity studies and examination of other affected members of the family permit the correct diagnosis to be made in such cases. It is also emphasized that patients similar to the one reported here may also resemble, and should be differentiated from, cases of familial dorsal column ataxia (Biemond type). Stress is put upon the fact that when Charcot-Marie-Tooth disease mimicks spino-cerebellar degeneration, substantial slowing of motor conduction in the upper limbs is generally sufficient to establish the diagnosis.

The relation between Friedreich’s ataxia and Charcot-Marie-Tooth disease is reviewed and it is concluded that these two disorders are distinct clinical and pathological entities.

The preliminary results based on a three year study on the evolution and management of scoliosis in Friedreich’s ataxia are presented. Thirty-two patients were followed in the Neuromuscular Disease Clinic at Sainte-Justine Hospital where standardized spinal radiographs were taken periodically with the Scoliosis Chariot and the Throne.

Pathomechanics — Between the age groups I (5 – 10 years) and II (10 – 15 years), a substantial increase in the Cobb values occurs. Associated with it, an increase was observed in the thoracic and thoraco-lumbar projected surface area indices. The relative torsion between the thoracic and lumbar segments was associated with a sudden increase in the Cobb measurements.

A computer program which generates a tri-dimensional display of the spine from the coordinates obtained from the standardized radiographs has been adapted to study the importance and influence of the thoracic torsion on the progress of the scoliosis and on the evolution of the total spinal deformity.

Management — Prevention of the progression of established curves was our main objective. Careful examination of the spine, depending on the age of the child, in our preliminary study, stimulated early orthopaedic treatment in any curve of 20° or more. There was always concern for curves of 30° or more. In the growing child, bracing which was recommended is now under a more thorough investigation. The use of spinal pacemakers is being clinically evaluated.

In the older child, the curve was usually stable after sixteen years of age. Surgery was usually attempted in curves over 40° in the growing child. The same curve was usually stable after the growth period.

For the non-ambulatory patients, the present study suggested the prescription of a molded seat with the following characteristics: i) a posterior lumbar support, ii) low thoracic lateral supports and Hi) a slight inclination of the seating system. This was presumed to be beneficial in maintaining stability of the spine.

The preliminary results based on a three year retrospective study in cavus foot deformity of forty-four Friedreich ataxia patients regularly seen at the Neuromuscular Disease Clinic of Sainte-Justine Hospital have been presented. An accurate “weight-bearing” foot stereoradiographic technique has been recently developed by our group. Since the follow-up period with this device is not sufficient to provide statistical information, the conventional non-weight bearing technique has been utilized in this study to enable a possible comparison between the radiographs of ambulant and non-ambulant patients. Due to the present technique, the results of this study must be interpreted with caution.

For 132 pairs of radiographs, 28 parameters have been analyzed. Four of these, namely the calcaneal inclination angle, the first metatarsal inclination angle, the inferior cortex of calcaneus-first metatarsal angle and the first-fifth metatarsals angle, were of particular interest. From these parameters, a preliminary quantitative description of cavus foot deformity in Friedreich’s ataxia has been attempted. Three stages of evolution have been tentatively identified for this type of neurological disorder.

Orthogonal stereoradiographs are frequently utilized in determining three-dimensional geometrical parameters of human body segments. They have been applied here in the estimation of the length and elongation of the ligaments of the normal foot. Three small spherical metallic markers were respectively encrusted into the tibia and fibula, the seven bones of the tarsus and into the five metatarsals of an amputed lower limb to identify uniquely their spatial location. The foot was then positioned on a rotating platform. Standardized antero-posterior and lateral radiographs were taken. Afterwards the foot was dissected and the proximal and distal insertions of most of its ligaments were located by means of spherical markers. A second series of orthogonal radiographs were taken of each of the fourteen bones. The radiographs were digitized. The length of each ligament and elongation for a simple and complex movements were calculated by means of a computer program. The results of a simple movement of rotation representing a normal 20° dorsiflexion at the talocrural joint and of complex movements of rotation simulating an abnormal high arch such as encountered in Friedreich’s ataxia are presented and discussed.

Seventeen patients with Friedreich’s ataxia or spastic ataxia were subjected to an urodynamic evaluation. Fifty-three per cent (53%) of the patients presented with urinary symptoms consisting of urgent micturition and urgency incontinence. Cystometric evaluation showed a lack of inhibition of the detrusor in 7 patients (41%). Abnormal electric hyperactivity of the external sphincter was documented in 6 cases (37.5%) by electromyography. Some hypotheses are presented to explain the etiology of these abnormal findings.

Auditory brainstem responses (ABRs) and cortical auditory evoked responses (AERs) were studied in a series of 16 Friedreich’s ataxia patients who varied in age, degree of clinical involvement and duration of the disorder. The ABRs were markedly abnormal in all but the youngest patient, and the abnormalities reflected the severity and duration of the disease. The latencies of the AERs were significantly longer in the Friedreich’s ataxia patients compared to normal controls, suggesting cortical as well as peripheral involvement of the auditory system. These data are discussed in terms of the neuropathology of the disorder and the similarities with the other sensory systems in Friedreich’s ataxia patients.

We report the preliminary study of a dorsal root ganglion obtained at biopsy during a surgical intervention in a patient with Friedreich’s ataxia. There was an apparent decrease in the number of large myelinated fibers without necrosis, but with numerous axonal swellings consisting mainly of dense accumulated neurofilaments. Large amounts of lipofuscin were also found as well as some onion bulb formations suggesting a process of axonal atrophy.

Threonine supplementation (500 mg/day) was given to 6 patients with genetic spasticity syndromes for a period of 12 months, followed by a 4-month observation period without medication. All 6 patients showed partial improvement of spasticity, intensity of knee jerks and muscle spasms without changes in true pyramidal tract signs. The improvement in motor performance, objectively measured, averaged 29% (19% in upper limbs and 42% in lower limbs). The range of overall improvement was 19–35% (7–30% for upper limbs; 25–67% for lower limbs). No toxic clinical or biochemical side effects were encountered. Thus threonine, a precursor of glycine, produced the same effect on spasticity than that previously observed with glycine. It is concluded that threonine supplementation is feasible and safe and that it deserves a controlled trial in well defined (preferably genetic) cases of spasticity.

In a six-month open pilot study, pure phosphatidylcholine was administered intravenously (2.5g daily for a month) and orally (5g daily for five months) to sixteen patients with Friedreich’s ataxia (FA) and seven patients with other inherited ataxias. Only the oral treatment achieved a mild but significant, 25% improvement, mainly of “central” symptoms in the FA patients at stage 2 of the illness, that is, still able to walk without support and to lead an independent life. However, the drug was ineffective in the more advanced cases. These results are discussed and compared with those obtained with lecithin by other authors.

A clinical and biochemical evaluation of twenty-two patients with Friedreich’s Ataxia and ten normal controls was undertaken in 1980 to assess the effect of lecithin and linoleic acid supplements on the course of the disease. The trial consisted of two consecutive six months periods on either supplements in a double-blind crossover fashion. Clinical appraisal was performed with regards to the following parameters: joints mobility, muscle strength, equilibrium, coordination, motor accuracy, speech and numerous day to day activities. Blood samples were obtained at the beginning and in the course of the trial for enzymatic determinations. This paper describes the methodology of the study.

Twenty-two patients with Friedreich’s Ataxia and ten normal controls were followed for one year and assessed as to their clinical performance after two successive six-month periods of lecithin or safflower oil. Results demonstrated no significant difference in performance scores according to group assignation, neither in patients nor in controls. According to stages, two patients in stage I and to a lesser degree, one patient in stage IV showed better scores for muscle strength and some motor accuracy and coordination tests with lecithin. Controls as groups maintained positive scores in all tests. Patients as groups showed negative mean values in nine out of eleven tests. Again as groups, patients receiving safflower oil demonstrated a mean 8% less deterioration than patients receiving lecithin. This study demonstrates that objective clinical tests and the participation of normal controls are a must in a therapeutic trial implicating patients with a progressive disorder such as Friedreich’s Ataxia. The possible role of linoleic acid as the active factor from which clinical improvement proceeded in some specific patients and with early functional stages of the disease, has to be considered and reevaluated in the near future.

Lecithin and sqfflower oil brought about the same changes in serum LAD activity and kinetics in patients with Friedreich’s Ataxia as in controls when results of this double-blind crossover study were analyzed according to group assignation. According to functional stages, pretrial LAD activity decreased with advancing severity while Km for lipoamide increased. Lecithin and sqfflower oil supplements corrected the elevated Km for lipoamide but produced a further reduction in LAD activity. These changes may have been due to the increased intake of linoleic acid, a precursor of lipoic acid, which is present in high percentage in both lecithin and safflower oil. Results of the biochemical study thus agreed with the clinical data gathered during the course of the one-year trial in suggesting that linoleic acid may well have been the active factor through which biochemical and clinical improvement was previously observed in patients with Friedreich’s Ataxia supplemented with lecithin.

Gamma-Vinyl GABA, an irreversible inhibitor of GABA-transaminase, was administered orally in two daily doses of 250 mg to 10 patients with cerebellar ataxia (9 with Friedreich’s ataxia, one with olivo-ponto-cerebellar atrophy) for at least one month in an open study. No significant difference occurred in the disability scores of cerebellar symptomatology for the group as a whole, but seven patients showed some improvement in scores with treatment and two patients claimed marked subjective amelioration. Tolerance to Gamma-Vinyl-GABA treatment was excellent. These preliminary results suggest that further studies with well-tolerated agents which enhance CNS GABA-ergic function are warranted in patients with cerebellar ataxia.

The purpose of the present study was to examine the ability of nicotinamide to prevent the appearance of neurobehavioral symptoms induced by 3-acetyl pyridine (3-AP) in rats. Nicotinamide in doses of 5,50 and 500 mg/kg was injected immediately after administration of 65 mg/kg 3-AP, and neurobehavioral measurements were made at 6, 12, 24, 48 and 72 hours after injections. The effects of 500 mg/kg nicotinamide injected at 3 and 6 hours after 3-AP treatment were also investigated. The results indicate that, starting at 50 mg/kg, nicotinamide can protect animals against most of the neurobehavioral effects of 3-AP. However, the muscular rigidity induced by 3-AP can only be reversed by 500 mg/kg nicotinamide, and the depressing influence of 3-AP on locomotor activity is not blocked by any of the doses of nicotinamide tested. In terms of time course, the protective action of 500 mg/kg is seen when injected 3, but not 6 hours after 3-AP.